, p < .0001). Intraoperative frozen section and DJ
ureteric stenting (general costs) (p <= .008) and haemostatic agents use (p <=
.01) were higher in nephron sparing surgery (NSS), due to more frequent use of
ancillary procedures necessary for a safe management of such an approach.
Estimated anaesthesia costs and doctor/nurses fee were higher in MIS (p <= .02).
Whereas total final reimbursements were comparable (p >= .8), estimated daily
reimbursements were lower in MIS (p < .001) due to higher intraoperative costs
and longer operative time. CONCLUSION: Well-known advantages offered by MIS/NSS
face higher total intraoperative costs and 'paradoxical' reduced healthcare
reimbursement. We believe that local health systems should consider a
subclassification with different compensations, which will incentive NSS and MIS
approaches.
PMID- 24346846
TI - Yamadazyma ubonensis f.a., sp. nov., a novel xylitol-producing yeast species
isolated in Thailand.
AB - Three hundred and thirty-seven xylose-utilizing yeast strains were isolated from
various natural samples. Among these, 68 strains produced xylitol in the range of
0.1-0.69 g xylitol/g xylose. Thirty-nine xylitol-producing strains were
identified to be Candida tropicalis. Ten strains were found belonging to 14 known
species in the genus Candida, Cyberlindnera, Meyerozyma, Pichia, Wickerhamomyces,
Yamadazyma and Cryptococcus. Two strains were identified to be two Candida
species and two strains (DMKU-XE142(T) and DMKU-XE332) were found to be a novel
species. Strain DMKU-XE142(T) was isolated from tree bark and DMKU-XE332 was
obtained from decaying plant leaf collected in Thailand. On the basis of
morphological, biochemical, physiological and chemotaxonomic characteristics and
sequence analysis of the D1/D2 region of the large subunit rRNA gene (LSU) and
the internal transcribed spacer (ITS) region, the two strains were determined to
represent a novel Yamadazyma species although formation of ascospores was not
observed. The sequences of the D1/D2 region of the LSU rRNA gene and the ITS
region of the two strains were identical but differed from Yamadazyma
phyllophila, the closest species in terms of pairwise sequence similarity of the
D1/D2 region, by 1.7 % nucleotide substitutions and 3.5 % nucleotide
substitutions in the ITS region. The name Yamadazyma ubonensis f.a., sp. nov. is
proposed (type strain is DMKU-XE142(T) = BCC 61020(T) = CBS 12859(T)).
PMID- 24346847
TI - Maspin expression, subcellular localization and clinicopathological correlation
in endometrial hyperplasia and endometrial adenocarcinoma.
AB - Maspin expression in endometrial hyperplasia and endometrial endometrioid
adenocarcinomas was assessed and its correlation with p53 and Ki67 expressions
and clinical outcome, as well as its potential to distinguish typical from
atypical endometrial hyperplasia, were assessed in this study. Histological
sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of
endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue
samples were examined. The most representative hematoxylin-eosin slides were
selected and 2-3 micron-thick sections were cut for immunohistochemical staining
with maspin, p53, and Ki67 antibodies. While there was no maspin expression in
normal endometrial cells, it was present in 14.5% of the patients with
endometrial hyperplasia without atypia. Staining for maspin was positive in
atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and
49.1% of the cases studied. No statistically significant correlations were found
between maspin and Ki-67 antibodies or p53 expression. Our findings showed that
maspin expression, which generally correlates with a less aggressive behavior, is
significantly higher in atypical hyperplasia and in endometrial endometrioid
adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to
identify pseudo-atypical hyperplasia and could be considered a potentially useful
prognostic parameter in those cases in which adenocarcinomas are well
differentiated.
PMID- 24346848
TI - A time to weep and a time to laugh: humour in the nurse-patient relationship in
an adult cancer setting.
AB - PURPOSE: The literature highlights the value of humour in health-care settings.
Humour impacts on the physiological, psychosocial and cognitive well-being of a
person. The diagnosis of cancer is extremely stressful, and treatments are
difficult. Patients and nurses may use humour as a coping mechanism to contend
with the stresses caused directly or indirectly by cancer. This study
investigated the use of humour during interactions between patients and nurses in
an adult cancer ward. METHODS: This study used a modified ethnographic
methodology that included fieldwork participant observation and informal
interviews (n=30 h) and formal interviews (n=10). In total, 9 nurses and 12
patients participated in participant observation. From these, five nurses and
five patients were interviewed. Data were analysed using thematic analysis.
RESULTS: Findings highlighted the importance of humour in the nurse-patient
relationship. Patients consciously use humour during nurse-patient interactions
in an attempt to help nurses cope with the stress they encounter in clinical
practice. Patients perceive having a sense of humour as a positive nurse
attribute. Nurses expressed concerns regarding compromising professionalism when
using humour and felt the need for guidance from senior staff. Constant
assessment and reflection help ensure humour is used appropriately in the adult
health-care setting. CONCLUSION: The benefits of humour are recognised by both
adult cancer patients and nurses. A deeper understanding of patient and nurse
perceptions of the use of humour can inform strategies for its therapeutic use in
the clinical setting.
PMID- 24346849
TI - Pharmacokinetic-pharmacodynamic evaluation of the major component astragaloside
IV on the immunomodulatory effects of Yu-ping-feng prescription.
AB - Yu-ping-feng decoction (YPF), a traditional Chinese medicine (TCM) prescription,
is widely used to treat some respiratory tract diseases. This study was aimed to
set up a pharmacokinetic-pharmacodynamic (PK-PD) model to assess dose-effect
relationships for immunomodulatory effects of YPF in rats and to clarify
compatibility mechanisms for TCM prescription system. Serum samples taken after
YPF administration were tested on spleen cells of rats in vitro and proliferation
ratio of spleen cells was used as end points to evaluate pharmacodynamic
properties of immunoregulatory effects of YPF prescription. And with a HPLC-MS
method, concentrations of Astragaloside IV (AS), a main component of YPF, were
determined to achieve pharmacokinetic parameters after administration of a
simplified prescription which is composed with AS, Atractylenolide I and Prim-O
glucosylcimifugin which are representative components of YPF. A plot of serum AS
concentrations versus time and effects showed that there was a correlated
relationship between AS concentrations and effects of YPF, and the concentration
response curve which was based on an E max model showed a counterclockwise
hysteresis manner. A PK-PD model with Sheiner's method was used to describe time
course of AS concentration in blood compartment and effect compartment, and main
parameters with the PK-PD model were calculated. These results showed that there
is a symmetry relationship between serum AS concentrations and responses of serum
containing medicine of YPF prescription, which means that AS plays an important
role in immunoregulatory effects of YPF. And the investigation on dose-effect
relationships has displayed a feasible method to clarify mechanisms of
combination for TCM prescriptions.
PMID- 24346850
TI - Effects of silymarin on the pharmacokinetics of atorvastatin in diabetic rats.
AB - The effect of silymarin (SMN) on the pharmacokinetics of atorvastatin in diabetic
rats was evaluated. Male Wistar rats were assigned into two major groups and then
sub-grouped according to the purposes of the study. The first major group was
subdivided into three groups (n = 6) including control, non-treated diabetic and
SMN-treated diabetic animals. In the first major group, metabolism of
testosterone by the hepatic microsomes was studied. The second major group also
was divided to three groups including atorvastatin-treated non-diabetic,
atorvastatin-treated diabetic and diabetic animals which received both
atorvastatin and SMN. To study the pharmacokinetics of atorvastatin, serum
samples were collected at 0, 3, 6, 12 and 24 h after the atorvastatin
administration. Pharmacokinetic parameters were calculated using non
compartmental model. Streptozotocin-induced diabetes resulted in a remarkable
induction of testosterone hydroxylation as the V max for 6beta
hydroxytestosterone production in the diabetic rats (77.3 +/- 8.6 pM/min/mg) was
significantly higher than that in the control animals (45.9 +/- 5.9 pM/min/mg).
Moreover, SMN-treated animals showed a significant (P < 0.05) reduction of V max
(59.4 +/- 6.1 pM/min/mg). Diabetes resulted in a significant reduction of AUC
(control 6.98 +/- 0.58 vs diabetic rats 4.35 +/- 0.24 h mg/ml) and C max values
(control 0.52 +/- 0.03 vs diabetic group 0.33 +/- 0.01 MUg/ml), while the SMN
received group showed remarkable recovery of diabetes-reduced values of AUC and C
max. These findings indicated that diabetes resulted in a significant up
regulation of microsomal enzyme activities. Moreover, as SMN could significantly
regulate the enzyme activities and consequently the atorvastatin pharmacokinetics
in diabetic rats, its regulative effect in a combination therapy is concluded.
PMID- 24346851
TI - Gender differences in pharmacokinetics of a combination tablet of niacin extended
release/simvastatin in healthy Chinese volunteers.
AB - The gender differences in pharmacokinetics of a combination tablet of niacin
extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty
six healthy male and female volunteers were enrolled in the study receiving a
single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results
indicated that the systemic exposure of simvastatin hydroxy acid and the total
urine excretion of niacin were significantly higher for females compared with
those for males, and the T max of niacin in plasma was significantly shorter for
males than that for females. There were no significant differences in the
systemic exposure of simvastatin, niacin, and NUA in plasma between males and
females.
PMID- 24346854
TI - Elastic stiffness characterization using three-dimensional full-field deformation
obtained with optical coherence tomography and digital volume correlation.
AB - This paper presents a methodology for stiffness identification from depth
resolved three-dimensional (3-D) full-field deformation fields. These were
obtained by performing digital volume correlation on optical coherence tomography
volume reconstructions of silicone rubber phantoms. The effect of noise and
reconstruction uncertainties on the performance of the correlation algorithm was
first evaluated through stationary and rigid body translation tests to give an
indication of the minimum strain that can be reliably measured. The phantoms were
then tested under tension, and the 3-D deformation fields were used to identify
the elastic constitutive parameters using a 3-D manually defined virtual fields
method. The identification results for the cases of uniform and heterogeneous
strain fields were compared with those calculated analytically through the
constant uniaxial stress assumption, showing good agreement.
PMID- 24346852
TI - Evolving concepts and treatment strategies for cardiac allograft vasculopathy.
AB - OPINION STATEMENT: The central event in the development of allograft vasculopathy
is the inflammatory response to immune-mediated and nonimmune-mediated
endothelial damage. This response is characterized by the release of inflammatory
cytokines, upregulation of cell-surface adhesion molecules, and subsequent
binding of leukocytes. Growth factors stimulate smooth muscle cell proliferation
and circulating progenitor cells are recruited to sites of arterial injury
leading to neointima formation. Because of its diffuse nature, intravascular
ultrasound is more sensitive than angiography for early diagnosis. Proliferation
signal inhibitors (PSIs) have the capacity to slow vasculopathy progression by
inhibiting smooth muscle cell proliferation, but its side effects profile makes
its use as a first line agent difficult. Retransplantation is still the only
definitive therapy but is available only in selected cases. The current hope is
that immunomodulation at the time of transplant could induce long-term tolerance
and graft accommodation, leading to less vasculopathy.
PMID- 24346853
TI - The Role of Treatment for Anemia as a Therapeutic Target in the Management of
Chronic Heart Failure: Insights After RED-HF.
AB - OPINION STATEMENT: Anemia is common in patients with heart failure (HF) and
appears to be closely linked with HF prognosis. A variety of mechanisms have been
implicated in the association between anemia and HF, and treatment of anemia as a
therapeutic target in HF patients is gaining increased attention. Recently large
randomized controlled trials of erythropoietin-stimulating agents (ESA) and
intravenous iron supplementation therapy have been completed and shed light on
treatment of anemia in HF patients. ESA therapy did not show improvement in
clinical outcomes, but intravenous iron supplementation may be of benefit in
improving HF symptoms. Anemia has been commonly reported in patients with chronic
heart failure (HF) and its prevalence appears to be closely linked with the
severity of HF. Furthermore, the presence of anemia in patients with HF has been
consistently associated with poor prognosis. Despite an increasing number of
studies evaluating the relationship between HF and anemia, the answer to whether
anemia is simply a marker or a mediator of poor prognosis in HF patients remains
uncertain. One approach to this pivotal question has been to investigate
treatment for anemia as a therapeutic target in HF.
PMID- 24346855
TI - Digital image correlation-based optical coherence elastography.
AB - Optical coherence elastography (OCE) provides deformation or material properties,
mapping of soft tissue. We aim to develop a robust speckle tracking OCE technique
with improved resolution and accuracy. A digital image correlation (DIC)-based
OCE technique was developed by combining an advanced DIC algorithm with optical
coherence tomography (OCT). System calibration and measurement error evaluation
demonstrated that this DIC-based OCE technique had a resolution of ~0.6 MUm
displacement and <0.5% strain measurement in the axial scan direction. The
measured displacement ranged from 0.6 to 150 MUm, obtained via phantom imaging.
The capability of the DIC-based OCE technique, for differentiation of stiffness,
was evaluated by imaging a candle gel phantom with an irregularly shaped stiff
inclusion. OCE imaging of a chicken breast sample differentiated the fat,
membrane, and muscle layers. Strain elastograms of an aneurysm sample showed
heterogeneity of the tissue and clear contrast between the adventitia and media.
These promising results demonstrated the capability of the DIC-based OCE for the
characterization of the various components of the tissue sample. Further
improvement of the system will be conducted to make this OCE technique a
practical tool for measuring and differentiating material properties of soft
tissue.
PMID- 24346856
TI - Enhanced fluorescence diffuse optical tomography with indocyanine green
encapsulating liposomes targeted to receptors for vascular endothelial growth
factor in tumor vasculature.
AB - To develop an indocyanine green (ICG) tracer with slower clearance kinetics, we
explored ICG-encapsulating liposomes (Lip) in three different formulations:
untargeted (Lip/ICG), targeted to vascular endothelial growth factor (VEGF)
receptors (scVEGF-Lip/ICG) by the receptor-binding moiety single-chain VEGF
(scVEGF), or decorated with inactivated scVEGF (inactive-Lip/ICG) that does not
bind to VEGF receptors. Experiments were conducted with tumor-bearing mice that
were placed in a scattering medium with tumors located at imaging depths of
either 1.5 or 2.0 cm. Near-infrared fluorescence diffuse optical tomography that
provides depth-resolved spatial distributions of fluorescence in tumor was used
for the detection of postinjection fluorescent signals. All liposome-based
tracers, as well as free ICG, were injected intravenously into mice in the
amounts corresponding to 5 nmol of ICG/mouse, and the kinetics of increase and
decrease of fluorescent signals in tumors were monitored. A signal from free ICG
reached maximum at 15-min postinjection and then rapidly declined with t1/2 of
~20 min. The signals from untargeted Lip/ICG and inactive-Lip/ICG also reached
maximum at 15-min postinjection, however, declined somewhat slower than free ICG
with t1/2 of ~30 min. By contrast, a signal from targeted scVEGF-Lip/ICG grew
slower than that of all other tracers, reaching maximum at 30-min postinjection
and declined much slower than that of other tracers with t1/2 of ~90 min,
providing a more extended observation window. Higher scVEGF-Lip/ICG tumor
accumulation was further confirmed by the analysis of fluorescence on
cryosections of tumors that were harvested from animals at 400 min after
injection with different tracers.
PMID- 24346857
TI - Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the
head and neck.
AB - BACKGROUND: There is a need to improve the systemic treatment of advanced adenoid
cystic carcinoma (ACC). Response rates to chemotherapy are poor and preliminary
investigations of molecularly targeted agents have been disappointing. In this
study, we evaluate sorafenib, an oral multikinase inhibitor, which has an
attractive targeting profile for this disease. METHODS: In a single-arm phase II
trial, patients with unresectable locally recurrent and/or metastatic ACC were
treated with sorafenib 400 mg bid. RESULTS: Twenty-three patients, median age 51
years, were recruited from 2009 to 2011. Median progression-free survival (PFS)
and overall survival (OS) were 11.3 and 19.6 months, respectively. PFS at 6 and
12 months were 69.3% and 46.2%, respectively. Sorafenib was only reasonably well
tolerated, and 13 patients (57%) experienced grade 3 toxicity. CONCLUSION:
Sorafenib showed modest activity in ACC with a 12-month PFS of 46.2%. Sorafenib
400 mg bid was associated with significant toxicity and, taken together with
limited effectiveness, cannot be enthusiastically recommended for further
evaluation.
PMID- 24346858
TI - Temperature-driven switching of water adhesion on organogel surface.
AB - Temperature-driven switching of water adhesion is realized on a novel n
paraffinswollen organogel by thermally controlling the transition of
air/liquid/solid (ALS/ALLS) systems via the phasechange process of n-paraffin.
The thermal control of both the water-drop sliding motion and the switching of
the optical transparency shows potential applications in scientific research and
daily life.
PMID- 24346859
TI - Fish oil in comparison to folinic acid for protection against adverse effects of
methotrexate chemotherapy on bone.
AB - Methotrexate (MTX) chemotherapy is known to cause bone loss which lacks specific
preventative treatments, although clinically folinic acid is often used to reduce
MTX toxicity in soft tissues. This study investigated damaging effects of MTX
injections (0.75 mg/kg/day for 5 days) in rats and potential protective benefits
of fish oil (0.25, 0.5, or 0.75 ml/100 g/day) in comparison to folinic acid (0.75
mg/kg) in the tibial metaphysis. MTX treatment significantly reduced height of
primary spongiosa and volume of trabecular bone while reducing density of
osteoblasts. Consistently, MTX reduced osteogenic differentiation but increased
adipogenesis of bone marrow stromal cells, accompanied by lower mRNA expression
of osteogenic transcription factors Runx2 and Osx, but an up-regulation of
adipogenesis-related genes FABP4 and PPAR-gamma. MTX also increased osteoclast
density, bone marrow osteoclast formation, and mRNA expression of proinflammatory
cytokines IL-1, IL-6, TNF-alpha, and RANKL/OPG ratio in bone. Fish oil (0.5 or
0.75 ml/100 g) or folinic acid supplementation preserved bone volume, osteoblast
density, and osteogenic differentiation, and suppressed MTX-induced cytokine
expression, osteoclastogenesis, and adipogenesis. Thus, fish oil at 0.5 ml/100 g
or above is as effective as folinic acid in counteracting MTX-induced bone
damage, conserving bone formation, suppressing resorption and marrow adiposity,
suggesting its therapeutic potential in preventing bone loss during MTX
chemotherapy.
PMID- 24346860
TI - Assessing the exposure of lion tamarins (Leontopithecus spp.) to future climate
change.
AB - Understanding how biodiversity will respond to climate change is a major
challenge in conservation science. Climatic changes are likely to impose serious
threats to many organisms, especially those with narrow distribution ranges,
small populations and low dispersal capacity. Lion tamarins (Leontopithecus spp.)
are endangered primates endemic to Brazilian Atlantic Forest (BAF), and all four
living species are typical examples of these aggravating conditions. Here, we
integrate ecological niche modeling and GIS-based information about BAF remnants
and protected areas to estimate the exposure (i.e., the extent of climate change
predicted to be experienced by a species) of current suitable habitats to climate
change for 2050 and 2080, and to evaluate the efficacy of existing reserves to
protect climatically suitable areas. Niche models were built using Maxent and
then projected onto seven global circulation models derived from the A1B climatic
scenario. According to our projections, the occurrence area of L. caissara will
be little exposed to climate change. Western populations of L. chrysomelas could
be potentially exposed, while climatically suitable habitats will be maintained
only in part of the eastern region. Protected areas that presently harbor large
populations of L. chrysopygus and L. rosalia will not retain climatic suitability
by 2080. Monitoring trends of exposed populations and protecting areas predicted
to hold suitable conditions should be prioritized. Given the potential exposure
of key lion tamarin populations, we stress the importance of conducting
additional studies to assess other aspects of their vulnerability (i.e.,
sensitivity to climate and adaptive capacity) and, therefore, to provide a more
solid framework for future management decisions in the context of climate change.
PMID- 24346861
TI - Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma
cells.
AB - During the course of screens to identify anti-melanogenic agents from natural
resources, we found that the methanol extract of the dried flower of Inula
britannica L. inhibited melanin synthesis in cultured melanoma cells stimulated
with 3-isobutyl-1-methylxanthine (IBMX). A bioassay-guided isolation of the
chloroform fraction of the I. britannica using an in vitro melanogenesis
inhibition assay led to the isolation of sesquiterpenes, 1-O
acetylbritannilactone (1), britannilactone (2) and neobritannilactone B (3).
Compounds 1 and 2 significantly reduced melanin production in a dose-dependent
manner with IC50 values of 13.3 and 15.5 MUM, respectively, whereas compound 3
was found to be cytotoxic. Compound 1 also inhibited the tyrosinase activity only
in cell based-systems. Western blot analysis indicated that compound 1 inhibited
melanogenesis by activating extracellular signal-regulated kinase (ERK) and Akt
signaling and also inhibiting cAMP related binding protein, which regulates its
downstream pathway, including tyrosinase, tyrosinase related protein-1 and TRP-2.
These results demonstrated that compound 1, a major sesquiterpene from the
flowers of I. britannica, exhibited anti-melanogenic activity by suppression of
tyrosinase expression via ERK and Akt signaling. Taken together, our results
suggest that these compounds may act as potent natural skin-lightening agents.
PMID- 24346862
TI - Providing animal health services to the poor in Northern Ghana: rethinking the
role of community animal health workers?
AB - The Community Animal Health Workers (CAHWs) system has been promoted as an
alternative solution to providing animal health services in marginal areas. Yet,
access to quality animal health services still remains a fundamental problem for
livestock dependent communities. This paper uses the concepts of accessibility,
affordability, and transaction costs to examine the perceptions of livestock
keepers about the various animal health service providers. The empirical analysis
is based on a survey of 120 livestock-keeping households in the Tolon-Kumbungu
and Savelugu-Nanton districts in the Northern Region of Ghana. A multinomial
logit model was used to determine the factors that influence households' choice
of alternative animal health service providers. The results show that the
government para-vets are the most preferred type of animal health service
providers while CAHWs are the least preferred. Reasons for this observation
include high transaction costs and low performance resulting from limited
training. In areas with few or no government para-vets, farmers have resorted to
self-treatment or to selling sick animals for consumption, which has undesirable
health implications. These practices also result in significant financial losses
for farmers. This paper finds that the CAHWs' system is insufficient for
providing quality animal health services to the rural poor in marginal areas.
Therefore, market-smart alternative solutions requiring strong public sector
engagement to support livestock farmers in marginal areas and setting minimum
training standards for animal health service providers merit policy
consideration.
PMID- 24346863
TI - Statins inhibit tumor progression via an enhancer of zeste homolog 2-mediated
epigenetic alteration in colorectal cancer.
AB - While statin intake has been proven to reduce the risk of colorectal cancer
(CRC), the mechanism of antitumor effects and clinical significance in survival
benefits remain unclear. Statin-induced antiproliferative effects and its
underlying mechanism were examined using six CRC cell lines. Statins except
pravastatin showed antiproliferative effects (simvastatin >= fluvastatin >
atorvastatin) even though both of simvastatin and pravastatin could activate
mevalonate pathways, suggesting the statin-mediated antiproliferative effects
depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression
by downregulation of histone methyltransferase enhancer of zeste homolog 2
(EZH2), which acts as an epigenetic gene silencer. Additionally, the use of
simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced
further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from
downregulated EZH2 in CRC cells and synergistically led to considerable
antiproliferative effects. In the clinical setting, Statin intake (except
pravastatin) displayed the downregulated EZH2 expression and inversely
upregulated p27(KIP1) expression in the resected CRC by immunohistochemical
staining and resulted in the significantly better prognoses both in overall
survival (p = 0.02) and disease free survival (p < 0.01) compared to patients
without statin intake. Statins may inhibit tumor progression via an EZH2-mediated
epigenetic alteration, which results in survival benefits after resected CRC.
Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer
therapy by their synergistic effects in CRC.
PMID- 24346864
TI - Enema use among men who have sex with men: a behavioral epidemiologic study with
implications for HIV/STI prevention.
AB - Enema use or douching is a risk factor for HIV/STI in men who have sex with men
(MSM). However, few studies have explored enema use practices. We examined the
frequency of enema use, type of products used, and reasons to use and not to use
before and after receptive anal sex in a large sample of MSM (N = 4,992)
recruited from 16 U.S. cities. Through online surveys, we examined personal,
behavioral, and environmental factors associated with enema use. Most (52 %)
participants reported having douched at least once and 35 % reported douching
within the last 3 months. While most (88 %) reported enema use before receptive
anal sex, 28 % douched after receptive anal sex. Most participants (65 %) used
water to douche, 24 % added salt, soap, and/or antibacterial products to water,
and 30 % reported using commercially available products. Being a man of color,
HIV-positive, diagnosed with an STI, identifying as "versatile" in sex, and
having more than two unprotected sex partners were significantly associated with
recent enema use. Douching behavior appears closely associated with HIV/STI risk.
Douching with water may be a concern since it may increase HIV/STI infection by
damaging the epithelium. Development and promotion of a non-damaging, non-water
based enema specifically for use in anal sex are recommended. In addition, the
seemingly contradictory recommendations that water-based lubricant is recommended
for anal sex but water-based enemas are dangerous need to be reconciled into a
single consistent message.
PMID- 24346865
TI - Self-reported impulsivity, rather than sociosexuality, predicts women's
preferences for masculine features in male faces.
AB - Previous research has suggested that an individual's sociosexual orientation
(i.e., their willingness to engage in sexual behavior outside of long-term
relationships) may influence the qualities they find attractive in a potential
mate. Results, however, have not been consistent and, moreover, studies have
tended to draw from specific social groups. Here, we tested the relationship
between sociosexuality and female's preferences for masculinity in male faces,
using a diverse population. We furthermore investigated impulsivity alongside
sociosexuality, as this trait has been suggested as a "root" cause of variation
in sexual behavior (Cross, 2010) and thus may better explain variation in mate
choice. Results showed a significant association between increases in both
sociosexuality and two subcomponents of impulsivity and greater preferences for
masculine male features. Regression analysis suggested that a subcomponent of
impulsivity, namely lack of planning, was the primary determinant of preferences.
We discuss the implications these results have for our understanding of female
attraction to masculine features.
PMID- 24346866
TI - The faking orgasm scale for women: psychometric properties.
AB - The Faking Orgasm Scale for Women (FOS) was designed to assess women's self
reported motives for faking orgasm during oral sex and sexual intercourse.
Exploratory factor analysis (EFA) was conducted on the responses of 481
heterosexual undergraduate females (M age = 20.33 years, SD = 2.48). Results of
the EFA revealed that the FOS-Sexual Intercourse Subscale was composed of four
factors: (1) Altruistic Deceit, faking orgasm out of concern for a partner's
feelings; (2) Fear and Insecurity, faking orgasm to avoid negative emotions
associated with the sexual experience; (3) Elevated Arousal, a woman's attempt to
increase her own arousal through faking orgasm; and (4) Sexual Adjournment,
faking orgasm to end sex. The analysis of the FOS-Oral Sex Subscale yielded four
factors: (1) Altruistic Deceit; (2) Insecure Avoidance, faking orgasm to avoid
feelings of insecurity; (3) Elevated Arousal; and (4) Fear of Dysfunction, faking
orgasm to cope with concerns of being abnormal. Each factor of the two subscales
was found to have excellent internal consistency. Confirmatory factor analysis on
a separate sample of 398 heterosexual female undergraduates (M age = 20.52 years,
SD = 2.55) confirmed the factor structure of each subscale with excellent fit
statistics. The FOS should allow researchers and clinicians to better understand
why women fake orgasm. Deepening this understanding may serve future research
examining sexual desire, satisfaction, and dysfunction as well as have
applications in sex and couples' therapy.
PMID- 24346867
TI - Extradyadic involvement and relationship dissolution in heterosexual women
university students.
AB - This study examined the role of extradyadic involvement (EDI) in heterosexual
dating relationships among young adult females (N = 539). A considerable
percentage of participants (36 %) reported that they had engaged in an
extradyadic emotional or sexual relationship within the last 2 months. Results
from logistic regression analyses supported the general hypothesis that emotional
and sexual EDI were both significantly associated with relationship dissolution.
These associations remained strong even after controlling for participants' age,
relationship duration, and relationship quality. The findings also showed that
the strength of the association between acts of emotional or sexual extradyadic
behaviors and relationship dissolution was linked to relationship quality, gender
of the actor, and type of EDI (emotional vs. sexual). Specifically, compared to
participants who reported poor relationship quality, those who reported high
relationship quality were more likely to end the partnership if they reported
emotional or sexual EDI. Findings suggest that individuals in higher quality
relationships appear to have considerably more to lose in their relationship when
emotional or sexual EDI occurs. This, in part, may be because the more
satisfactory the relationship the more disillusionment one may feel when betrayed
by their romantic partner. Overall, the present findings underscore the
multifaceted nature of the relationships between EDI and relationship
dissolution. We call for more research that rigorously examines what contextual
factors influence young adults in dating relationships to dissolve relationships
following EDI.
PMID- 24346868
TI - A case of paraneoplastic pemphigus associated with Castleman's disease.
AB - We present a case of PNP associated with Castleman's Disease. We have also
reviewed the literature and described the characteristics of the two associated
diseases. Gene clonal rearrangement was done to help diagnosis. We used, in
addition, stereotactic radiosurgery which, as far as we know, has never before
been employed to treat PNP associated with Castleman's Disease. This produced a
good response, suggesting that it might be a good alternative treatment for PNP
associated with Castleman's Disease when it is too difficult to operate.
PMID- 24346869
TI - Clinical and surgical therapeutic approach in erithema elevatum diutinum--case
report.
AB - Erythema elevatum diutinum is a rare chronic cutaneous vasculitis which usually
affects adults. It is characterized by symmetrical and persistent papules,
plaques, and nodules. These lesions are usually located on the extensor surfaces
of the extremities. We report a case of erythema elevatum diutinum in which the
association of dapsone and surgical excision promoted complete remission of skin
lesions, providing a new approach to the treatments described in the literature.
PMID- 24346870
TI - Extra ocular sebaceous adenocarcinoma in HIV-positive patient--case report.
AB - Sebaceous adenocarcinoma is a rare adnexal tumor that can affect the skin and is
divided into ocular, a more common form and extra ocular, of a rarer occurrence.
We report the case of a patient diagnosed with Acquired Immune Deficiency
Syndrome (AIDS) who developed an extra ocular, bulky and fast-growing sebaceous
adenocarcinoma on the face. The literature has suggested that transplanted
patients and HIV-positive patients have an excess risk for developing adnexal
tumors, including sebaceous adenocarcinoma.
PMID- 24346871
TI - Biological agents: investigation into leprosy and other infectious diseases
before indication.
AB - Biological agents are widely used for various immune-mediated diseases, with
remarkable effectiveness in the treatment of rheumatoid arthritis (RA),
psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease.
However, attention needs to be drawn to the adverse effects of these therapies
and the risk of reactivating underlying granulomatous infectious diseases such as
tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of
this paper is to describe a case of leprosy in a patient with RA using anti-TNF
alfa, demonstrating the need for systematic investigation of skin lesions
suggestive of leprosy in patients who require rheumatoid arthritis therapeutic
treatment, especially in endemic regions like Brazil.
PMID- 24346872
TI - Exacerbation of recalcitrant cutaneous sarcoidosis with adalimumab--a paradoxical
effect? A case report.
AB - The paradoxical adverse effects of tumor necrosis factor-alpha (TNF-alpha)
antagonists have been described frequently as a result of the widespread use of
these drugs. Among the TNF-alpha blocking agents, few reports exist relating the
use of adalimumab in cutaneous sarcoidosis, although all of them show good
results. More recently, sarcoidosis onsets have been reported with various TNF
alpha inhibitors. The current case is, to our knowledge, the first to describe
the exacerbation of cutaneous lesions of sarcoidosis treated with adalimumab.
PMID- 24346873
TI - Psoriatic scarring alopecia.
AB - Psoriasis is a relatively frequent inflammatory dermatosis. Scarring alopecia due
to scalp psoriasis was first reported in 1972, but few reports have been written
since then, showing that this is a very rare complication of a common disorder.
We report a young Brazilian woman with longstanding scalp psoriasis, which
progressed to scaring alopecia.
PMID- 24346874
TI - Primary systemic amyloidosis, acquired cutis laxa and cutaneous mucinosis in a
patient with multiple myeloma.
AB - A 57-year-old woman presented with periorbital ecchymoses, laxity in skin folds,
polyneuropathy and bilateral carpal tunnel syndrome. A skin biopsy of the
axillary lesion demonstrated fragmentation of elastic fibers, but with a negative
von Kossa stain, consistent with cutis laxa. The diagnosis of primary systemic
amyloidosis was made by the presence of amyloid material in the eyelid using
histopathological techniques, besides this, the patient was also diagnosed with
purpura, polyneuropathy, bilateral carpal tunnel syndrome and monoclonal
gammopathy. She was diagnosed as suffering from multiple myeloma based on the
finding of 40% plasma cells in the bone marrow, component M in the urine and
anemia. The patient developed blisters with a clear content, confirmed as
mucinosis by the histopathological exam. The final diagnoses were: primary
systemic amyloidosis, acquired cutis laxa and mucinosis, all related to multiple
myeloma.
PMID- 24346875
TI - Analysis of mutations in the PIK3CA and FGFR3 genes in verrucous epidermal nevus.
AB - Verrucous epidermal nevi are congenital hamartomas composed of keratinocytes and
may occur alone or in association with developmental abnormalities. A close
relationship between variations in the PIK3CA and FGFR3 genes and the appearance
of nevi has been recently reported. Based on that, we performed molecular assays
for the identification of E542K, E545G/K and H1047R mutations in the PIK3CA gene
and of the R248C mutation in the FGFR3 gene. Interestingly, during the
amplification process, we did not observe the PCR product of exon 9 of the PIK3CA
gene, a region comprising amino acids 542-545. This strongly suggests the
occurrence of a microdeletion of that region and indicates a possible allelic
variant, which has not yet being described in the literature.
PMID- 24346876
TI - Acral pseudolymphomatous angiokeratoma: case report and literature review.
AB - The authors describe a case of a female patient with Acral Pseudolymphomatous
Angiokeratoma of Children, known as APACHE. It is a rare benign cutaneous
disease, of unknown etiology, characterized by multiple, asymptomatic
erythematous-violaceous papules and nodules, usually located unilaterally with
acral distribution. Today, this denomination is questionable, since there are
published reports of this disease in adults and in different locations.
Clinically, it is similar to an angiokeratoma, whereas hystologically, it
corresponds to a distinct type of pseudolymphoma. The immunohistochemical study
is required to distinguish APACHE from cutaneous lymphoma.
PMID- 24346877
TI - Calciphylaxis: a rare but potentially fatal event of chronic kidney disease. Case
report.
AB - Calciphylaxis or calcific uremic arteriolopathy is a rare cutaneous-systemic
disease occurring in patients with advanced chronic kidney disease. The classical
clinical picture is that of a necrotic and progressive skin ulcer of reticular
pattern, mostly in the lower legs and susceptible to local infection. It is a
product of mural calcification and occlusion of cutaneous and sub-cutaneous
arteries and arterioles. The authors report the case of a 73-year-old male
patient in his late stage of renal disease presenting severe necrotic cutaneous
ulcers on lower legs followed by local and systemic infection and death due to
sepse after parathyroidectomy.
PMID- 24346878
TI - Inguinal ulcerated sebaceous carcinoma: an unusual presentation.
AB - Sebaceous carcinoma is a rare and aggressive skin tumor. It can be located in any
area of the body, the most commonly involved area being the periorbital region.
It does not entail a typical clinical presentation, which explains the often late
diagnosis. The aim of this report is to outline the rarity of the disease and its
atypical clinical description, since to this day, inguinal ulcers with clinical
manifestation have not been reported. We present and discuss a case of sebaceous
carcinoma with an unusual clinical presentation, in an elderly male patient. The
precise approach to genital ulcers, as shown in this case, is a diagnostic
challenge that requires a great deal of effort on the part of the clinician.
PMID- 24346879
TI - Cowden Syndrome: report of a case and brief review of literature.
AB - We present the case of a female patient with facial cutaneous lesions, a
cobblestone-like pattern of the oral mucosa, and verruciform lesions on the hand
since her youth. She reported a history of breast cancer, endometrial cancer,
melanoma and multiple benign tumors and cysts. PTEN gene analysis was performed
and confirmed Cowden Syndrome, a rare genodermatosis with an autosomal dominant
pattern of inheritance, characterized by multiple hamartomas. The phosphatase and
tensin homolog (PTEN) gene negatively regulates cell proliferation and cell cycle
progression. Loss of PTEN function contributes to an increased risk of cancer. We
emphasize the importance of early detection and accurate management of Cowden
Syndrome.
PMID- 24346880
TI - Cutaneous metastasis of colon adenocarcinoma: case report and review of the
literature.
AB - Skin metastases from colorectal carcinoma are rare and signal advanced disease.
We present a case of an 80-year-old male with a large skin metastatic focus in
the lower abdomen, a year after resection of a colonic adenocarcinoma. The
patient had already finished receiving his first cycle of chemotherapy shortly
before the discovery of the abdominal nodules and at the same period a chest X
ray, revealed shadows at the base of the right lung.
PMID- 24346881
TI - Carcinomatous degeneration of pilonidal cyst with sacrum destruction and invasion
of the rectum.
AB - Malignant degeneration of pilonidal cysts is rare. The most common histologic
type is the squamous cell carcinoma, triggered by the chronic inflammatory
process. The growth of the lesion is typically slow. The diagnosis must be early
and the appropriate treatment is ample surgical resection, including the
presacral fascia. In some cases, as the present one, the diagnosis is made at a
stage when the disease has progressed and invaded adjacent structures. In these
cases the surgery involves multiple organ resection. We report the case of a
patient with carcinomatous degeneration of pilonidal cyst, with bulky disease
that extended up to the wall of the rectum. The treatment was extended resection,
sacrectomy and abominoperineal resection of the rectosigmoid with permanent
colostomy.
PMID- 24346882
TI - Congenital multiple clustered dermatofibroma and multiple eruptive
dermatofibromas--unusual presentations of a common entity.
AB - Dermatofibroma is one of the most common entities seen in dermatology clinical
practice. Several clinical subtypes have nevertheless been described, all of them
of uncommon occurrence. The authors present two rare clinical variants of
dermatofibromas: congenital multiple clustered dermatofibroma (the presented case
is the 4th congenital case to be reported so far) and multiple eruptive
dermatofibromas developing in the setting of a Sjogren's syndrome. Since the
uncommon subtypes may not be clinically evident, dermatologists should
familiarize themselves with their main features and we advise a high level of
clinical suspicion in order to reach the correct diagnosis.
PMID- 24346883
TI - Linear IgA bullous dermatosis: report of an exuberant case.
AB - Linear immunoglobulin A dermatosis is a rare autoimmune bullous disease, but the
most common autoimmune bullous dermatosis in children. We report a typical
exuberant case of linear IgA dermatosis in a ten-month old child, who showed good
response to treatment with corticosteroids and dapsone.
PMID- 24346884
TI - Vulvoperineal Crohn's disease responsive to metronidazole.
AB - Crohn's disease is a multisystem chronic granulomatous inflammatory disease that
primarily affects the gastrointestinal tract. In the majority of the cases, the
cutaneous manifestations follow the intestinal disease, but occasionally
dermatological lesions are the inaugural event and may constitute the only sign
of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by
months to years and may go unrecognized. Due to the paucity of reports of Crohn's
disease at this location and in the absence of randomized trials, there are no
standard treatments for the cutaneous disease. We describe the case of a 47 year
old woman with vulvoperineal Crohn's disease without digestive involvement, that
was successfully managed with metronidazole.
PMID- 24346885
TI - Systemic sclerosis with keloidal nodules.
AB - Nodular sclerosis is a rare form of presentation related to both systemic and
localized forms of scleroderma. We describe the case of a patient with nodular
sclerosis in order to alert the medical community to recognize this entity.
PMID- 24346886
TI - Diffuse systemic sclerosis with bullous lesions without systemic manifestations.
AB - Here, we describe an atypical case of systemic sclerosis in its diffuse cutaneous
form with acute and rapid progression of the cutaneous condition, without any
systemic manifestations and the infrequent formation of bullae, showing the
importance of diagnosis and early treatment in such cases. This case also shows
that special measures should be taken for bullous cutaneous lesions and
ulcerations resulting from serious sclerosis, which are entry points and increase
morbidity and risk of death. Other prognostic factors include age, ESR and renal
and pulmonary involvement. Capillaroscopies can be useful predictors of greater
severity of systemic scleroderma, revealing a greater link with systemic, rather
than cutaneous, involvement.
PMID- 24346887
TI - Eumycetoma by Madurella mycetomatis with 30 years of evolution: therapeutic
challenge.
AB - We report a case of eumycetoma by Madurella mycetomatis on the buttocks and
thighs in an adult immunocompetent patient, diagnosed after 30 years of clinical
development. He was treated over four years with fluconazol and itraconazol
associated with five times surgical excisions of subcutaneous nodules. At the
eighth year of follow-up, one nodule recurred on the right infragluteal region,
which was excised surgically and has remained asymptomatic ever since.
PMID- 24346888
TI - Phacomatosis pigmentovascularis type IIa--case report.
AB - Phacomatosis Pigmentovascularis is a rare syndrome characterized by capillary
malformation and pigmentary nevus. A case of a 2-year-old patient is reported,
who presented extensive nevus flammeus and an aberrant Mongolian spot, without
systemic disease, manifestations that allow us to classify this case as type IIa
Phacomatosis Pigmentovascularis, according to Hasegawa's classification.
PMID- 24346889
TI - Nodular fasciitis on the zygomatic region: a rare presentation.
AB - Nodular fasciitis is a benign tumor, resulting from reactive proliferation
composed of fibroblastic/myofibroblastic cells. Due to its rapid growth and high
cellularity it may be mistaken for sarcoma. Despite the possibility of
spontaneous regression, excision is the treatment of choice. A 24-year-old female
patient presented with a nodule on the zygomatic region with 3 months of
evolution. Excisional biopsy was performed. Histopathological examination
associated with immunohistochemical markers HHF35, AML and Ki-67 allowed
diagnostic confirmation. The main relevance of the case presented is its rare
location, suggesting its inclusion among the differential diagnoses of tumor
lesions on the face.
PMID- 24346890
TI - Lucio's phenomenon. Case study of an exceptional response to treatment
exclusively with multibacillary multidrug therapy.
AB - Lucio's phenomenon represents a serious cutaneous necrotizing reaction, which can
occur with Lucio's leprosy and also in other forms of lepromatous leprosy. The
authors discuss the case of a 63-year-old male patient presenting with ulcers and
necrotic cutaneous lesions on the limbs, torso and face, associated with
recurring sinusitis, hoarseness and a weight loss of 25 kilos over the last year.
Bacilloscopy of intradermal scrapings showed a bacilloscopic index of 5 and the
histopathological findings were compatible with the diagnosis of Lucio's
phenomenon. The chosen treatment was exclusively multibacillary multidrug
therapy, resulting in important dermatological improvement after one month of
therapy. The authors present an impressive case of Lucio's phenomenon with an
exceptional response to treatment exclusively with multibacillary multidrug
therapy.
PMID- 24346891
TI - Granuloma faciale: a rare disease from a dermoscopy perspective.
AB - The granuloma faciale is a rare and benign skin disease of unknown etiology,
characterized by chronic leukocitoclastic vasculitis. It is characterized by skin
lesions predominantly facial whose course is chronic and slowly progressive. The
diagnosis is based on clinical features, histopathology and, more recently, in
dermoscopy. We describe the case of a male patient, 40 years old, with a sarcoid
lesion on the malar site, whose histopathological examination revealed a mixed
inflammatory infiltrate with presence of Grenz zone. Dermoscopy revealed a pink
background with white striations. The definitive diagnosis is made by
histopathologic evaluation, and dermatoscopy can be helpful. It is known to be
resistant to therapy, oral medications, intralesional and surgical procedures are
options.
PMID- 24346892
TI - Perforating granuloma annulare mimicking papulonecrotic tuberculid.
AB - A case is reported of a patient presenting lymph node tuberculosis and cutaneous
lesions resembling papulonecrotic tuberculid, but histologically compatible with
perforating granuloma annulare and which responded satisfactorily to
antituberculous therapy. This is probably one of the first reports of the
association of perforating granuloma annulare and tuberculosis, and it is
important therefore to highlight the relevance of this disorder in the
differential diagnosis of papulonecrotic tuberculid and to raise the hypothesis
that this entity should also be considered to be a variant of tuberculid.
PMID- 24346893
TI - Indeterminate leprosy and lepromatous index case: four cases in the same family.
AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which
primarily affects the skin and peripheral nerves. Brazil remains as the country
with the second largest number of cases in the world. We report the case of three
patients diagnosed with indeterminate leprosy in the same family. Two patients
were HIV positive. An active search led to the discovery of the index case. It
was crucial to persist in the search of the index case. This report shows how
important it is to teach physicians and the general population about the signs
and symptoms of leprosy. Early diagnosis and treatment are necessary to prevent
sequelae and to eliminate the disease as a public health problem.
PMID- 24346894
TI - Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C
patient during treatment with interferon and ribavirin.
AB - Hepatitis C is an inflammatory disease of the liver caused by a single-stranded
RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called
the hepatitis C virus. After initial infection, 70% to 85% of the patients
develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver
changes, various extrahepatic manifestations have been associated with the
hepatitis C virus infection or with medications used to treat the condition. We
report the case of a patient with chronic hepatitis C who presented with the
signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four
months after the start of treatment with a pegylated interferon/ribavirin
combination.
PMID- 24346895
TI - Tufted angioma in ear auricle: importance of the differential diagnosis.
AB - Tufted angioma is an acquired vascular proliferation with specific histological
characteristics. The most common clinical features are erythematous macules. It
occurs predominantly in children and young adults, especially in the chest and
neck. We report the case of a male patient, 12 years old, with an increased right
ear auricle associated with erythematous macules and increased local temperature,
referred with a diagnosis of lepromatous leprosy; however, this diagnosis was
questioned. Histopathology was consistent with tufted angioma.
PMID- 24346896
TI - Mosaic epidermolytic ichthyosis--case report.
AB - Epidermolytic ichthyosis is a rare autosomal dominant disease that manifests at
birth with fragile blisters and erosions that evolve into hyperkeratotic lesions
associated or not with erythroderma. When the disease is associated with a
mutation in cytokeratin 1, it may be related to hyperkeratosis of palms and
soles, but this is not usually found when cytokeratin 10 is mutated. The disease
can present in a mosaic form, due to post zygotic mutation of the gene involved,
constituting an individual formed by two populations of genetically distinct
cells - one carrier of the mutation and the other without it. We report a case of
mosaic epidermolytic ichthyosis diagnosed in a female patient.
PMID- 24346897
TI - Implantation of autologous fat globules in localized scleroderma and idiopathic
lipoatrophy--report of five patients.
AB - A large number of diseases may cause Atrophic skin disorders are caused by a
large number of diseases, some of them idiopathic and others inflammatory, in
which there is loss of volume of body segments. Localized scleroderma is a rare
inflammatory dermatosis, manifested by atrophic skin and subcutaneous tissue
alterations. Lipoatrophy may be genetically inherited or acquired as a result of
panniculitis, HIV infections or aging. Many treatments have been proposed.
Results vary in the acute inflammatory phase and are scarce when sclerosis and
atrophy have already been established. This article describes four cases of
localized facial scleroderma and one of facial idiopathic lipoatrophy treated
with implantation of autologous fat globules extracted from the infragluteal
groove, without utilization of cannula aspiration, with lasting results.
PMID- 24346898
TI - Cutaneous leiomyomatosis in a mother and daughter.
AB - A 34-year-old woman with no known medical history was evaluated for multiple
painful brown nodules and papules on the anterior aspect of the trunk. She
mentioned a history of similar cutaneous findings on her mother. Biopsies of
three lesions revealed piloleiomyomata. Renal and adrenal ultrasound revealed an
isolated simple cortical cyst, and pelvic and endovaginal ultrasound revealed two
uterine myomata. The clinical diagnosis of hereditary leiomyomatosis and renal
cell cancer was corroborated by the identification of a heterozygous variant on
exon 5 of the fumarate hydratase gene (c.578C>T p.T193I). Identification of the
tumor piloleiomyoma should alert the dermatologist to this rare genodermatosis,
which is associated with an increased risk of renal cell tumors, demanding
multidisciplinary follow-up, and personal and family counseling.
PMID- 24346899
TI - Lymphocytoma cutis--case report.
AB - We describe a clinical case involving a 62-year-old white male, diagnosed with
lymphocytoma cutis (Spiegler-Fendt sarcoid) in the cephalic segment. The
diagnosis was carried out by pathological study and confirmed by
immunohistochemical panel: evidence of polyclonality. Phototherapy sessions were
suggested as treatment (13 PUVA sessions, with an accumulated dose of 58.65 J/cm2
). The improvement was partial. Thus, infiltration of triamcinolone was opted for
(one intralesional infiltration every 3 weeks). After 5 sessions, satisfactory
improvement was observed: regression of nearly all the lesions.
PMID- 24346900
TI - Primary cutaneous anaplastic large-cell lymphoma--case report.
AB - Primary cutaneous anaplastic large-cell lymphoma is part of the spectrum of CD30+
lymphoproliferative cutaneous processes, characterized by single or multifocal
nodules that ulcerate, are autoregressive and recurrent. Extracutaneous
dissemination may occur, especially to regional lymph nodes. Histology shows a
diffuse, non-epidermotropic infiltrate , anaplastic large lymphoid cells of
immunohistochemistry CD30+, CD4+, EMA-/+, ALK-, CD15- and TIA1-/+. Prognosis is
good and does not depend on lymphatic invasion. Radiotherapy, removal of the
lesion and/or low-dose methotrexate are the treatments of choice. The present
study reports the case of a 57-year-old-woman presenting Primary cutaneous
anaplastic large-cell lymphoma with multifocal lesions. The patient evolved with
pulmonary involvement 7 years later. She showed a good response to the treatment
with low-dose methotrexate prescribed weekly.
PMID- 24346901
TI - Primary cutaneous centrofollicular lymphoma with a good response to radiotherapy.
AB - Primary cutaneous lymphomas have different clinical behavior and prognosis than
systemic lymphomas of similar histological subtype. About 30% of non-Hodgkin
lymphomas involve extranodal tissues, the skin being the second most affected
body organ after the gastrointestinal tract (approximately 18%). According to the
EORTC (European Organization for Research and Treatment of Cancer)
classification, the lymphoma centrofollicular is indolent, since the lesions
increase in size slowly over the years and spread to extracutaneous sites is
uncommon. Based on this, radiotherapy has been considered the treatment of choice
by many studies. We present the case of a patient who had cutaneous
centrofollicular scalp lymphoma for 1 year and showed good response to
radiotherapy.
PMID- 24346902
TI - Linear lichen planus in children--case report.
AB - Lichen planus is an uncommon disease in children, and only 2 to 3% of affected
patients are under twenty years of age. This dermatosis may appear in several
clinical forms, which vary according to the morphology and distribution of
lesions. In less than 0.2% of all lichen planus cases, the lesions are
distributed along the lines of Blaschko, and is a variant called linear lichen
planus. This is a case report of a patient aged two years and eight months, who
presented keratotic violaceous papules, affecting the abdomen, buttocks and right
thigh, distributed along the lines of Blaschko. Histopathological examination
confirmed a diagnosis of linear lichen planus.
PMID- 24346903
TI - Agminate lichen aureus.
AB - Lichen aureus is a rare variant of pigmented purpura, with a chronic and benign
course. It is generally asymptomatic and often occurs in the lower limbs,
presenting as erythematous brownish, coppery or golden macules and/or papules.
The diagnosis is based on clinical and histopathological findings. The
dermatoscopic pattern has been considered a useful tool in diagnosis presumption.
We describe a case with a confluent morphological pattern, called agminate lichen
aureus.
PMID- 24346904
TI - Lichen planus pigmentosus inversus.
AB - Twenty-five year old male patient presenting with asymptomatic brown spots, on
cervical, axillary, inguinal and popliteal regions, for the last nine months.
Pathological examination showed hydropic degeneration of the basal layer,
pigmentary incontinence and moderate inflammatory lymphocytic infiltrate in the
dermis. Lichen planus pigmentosus inversus is a rare subtype of lichen planus
characterized by hyperchromic, asymptomatic or mildly pruritic macules, measuring
from millimeters to centimeters in diameter, with defined borders, affecting
intertriginous areas, most commonly in the axillae and groin of Caucasian
patients. It presents unique lichenoid histology. We report a case with typical
clinical features, histology and evolution.
PMID- 24346905
TI - Pyoderma gangrenosum with renal and splenic impairment--case report.
AB - Pyoderma gangrenosum is an uncommon and recurrent neutrophilic dermatosis of
unknown cause. The lesions usually start as tender sterile papulopustules or
erythematous nodules that undergo necrosis followed by ulceration. The lower
limbs are most commonly affected and around half of the cases are associated with
systemic disorders. Although rare, cases of pyoderma gangrenosum with
extramucocutaneous sterile neutrophilic infiltrate have been reported, with the
lungs being the most commonly affected organ. We report a case of pyoderma
gangrenosum with splenic and renal impairment. Pyoderma gangrenosum should be
considered a multisystemic disease with classic cutaneous manifestations and
potential involvement of internal organs.
PMID- 24346906
TI - Subcutaneous fat necrosis of the newborn: clinical manifestations in two cases.
AB - Subcutaneous fat necrosis of the newborn is an unusual form of panniculitis, with
few cases described in medical literature. The disease affects newborns at term
or post-term, with normal general health. We describe two cases of newborns
affected by the disease. One of them already had lesions since birth. Also, we
discuss the use of puncture for diagnostic assistance.
PMID- 24346907
TI - Blastic plasmacytoid dendritic cell neoplasm.
AB - Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive
hematodermic neoplasia with frequent cutaneous involvement and leukemic
dissemination. We report the case of a 76-year-old man with a 2 month history of
violaceous nodules and a tumor with stony consistency, located on the head, and
mandibular, cervical and supraclavicular lymphadenopathies. Multiple thoracic and
abdominal adenopathies were identified on computerized tomography. Flow cytometry
analysis of the skin, lymph node and bone marrow biopsies demonstrated the
presence of plasmocytoid dendritic cell neoplastic precursor cells (CD4+, CD45+,
CD56+ and CD123+ phenotype). After initial clinical and laboratorial complete
remission with chemotherapy, the patient died due to relapse of the disease
associated with the appearance of a cervical mass with medullary compromise.
PMID- 24346908
TI - Optic neuritis due to immunobiologics: first Brazilian case report.
AB - The change in immunological response obtained by immunobiologics has brought a
new paradigm to the treatment of immune-mediated disorders. As a result of their
efficacy, there is a positive impact on the quality of life of patients. However,
severe side effects, such as demyelination of cerebral or peripheral nerves, have
been reported. After review of literature using PubMed and MEDLINE data from 2000
to 2012, we identified the cases correlating the biological uniterms and optic
neuritis. This article reports the first Brazilian optic neuritis case associated
with the use of immunobiologics. This publication is justified by the rarity of
the disease and atypical therapeutical evolution.
PMID- 24346909
TI - Diffuse neurofibroma--an uncommon cause of alopecia.
AB - Although infrequent, alopecia can be caused by benign cutaneous tumours.
Neurofibromas are common benign tumors that originate in the peripheral nerve
sheath. Diffuse neurofibroma is a rare variant of neurofibroma that is thought to
occur mainly in the head and neck of children and young adults. Histology
generally shows an infiltrative tumor, composed of spindle cells in the dermis
and subcutaneous tissue. Despite being rare, malignant transformation has been
reported. The association between diffuse neurofibromas and neurofibromatosis
type 1 still remains to be determined since some authors question the low
incidence usually described. We report the case of a 42-year-old man who had a
diffuse neurofibroma on the scalp presenting as alopecic plaques.
PMID- 24346910
TI - Congenital agminated melanocytic nevus--case report.
AB - Agminated nevus is a cluster group of melanocytic nevi confined to a localized
area of the body. There are many pigmented lesions described in the literature as
agminated, such as blue nevi, multiple lentigines and Spitz nevi, but only a few
cases of congenital agminated melanocytic nevi have been described. We report a
case of a male child who presented with congenital agminated nevi, emphasizing
the importance of physical examination, dermoscopy, histopathological evaluation,
differential diagnosis and follow up to rule out the possibility of dysplastic or
malignant changes.
PMID- 24346911
TI - Pyoderma gangrenosum in a newborn--case report.
AB - Pyoderma gangrenosum is a rare, inflammatory, chronic and recurrent disease of
unknown etiology, characterized by noninfectious, necrotizing and painful
cutaneous ulcers. Usually it affects adults aged between 25 and 54 years old and
rarely children (less than 4%), in which it mainly affects the head, face,
buttocks, genital and perianal region. The disease presents a quick response to
systemic corticosteroids. We report a case of a newborn with hemorrhagic and
necrotic ulcers, distributed in the abdomen, buttocks and genital region with
rapid and effective response to oral prednisone.
PMID- 24346912
TI - Pyoderma gangrenosum: skin grafting and hyperbaric oxygen as adjuvants in the
treatment of a deep and extensive ulcer.
AB - Pyoderma gangrenosum is a rare dermatosis of unknown etiology and variable
clinical presentation. The disease is challenging for the medical staff, from the
frequent diagnostic difficulties to the lack of scientific evidence with a good
level to support the management of extensive and refractory cases. Our patient is
a 50 year-old man with an extensive and deep ulcer on the left leg, which
exemplifies the therapeutic difficulties inherent to the disease and who,
fortunately, has progressed with excellent result after association of hyperbaric
oxygen therapy and skin grafting to the immunosuppression therapy initially
proposed.
PMID- 24346913
TI - Porokeratosis of Mibelli--literature review and a case report.
AB - Porokeratosis is a disorder of epidermal keratinization characterized by annular
plaques with an atrophic center and hyperkeratotic edges, and includes a
heterogeneous group of disorders that are mostly inherited in an autosomal
dominant form. This report describes a 5 year-old female patient, with
porokeratosis of Mibelli confirmed histopathologically. The rarity of this
disorder, its clinical exuberance and the destructive character of the lesions,
as well as the facial and mucosal involvements, unusual in this form of
porokeratosis, and also its onset in early childhood motivated this report.
PMID- 24346914
TI - Cutaneous protothecosis--case report.
AB - Cutaneous protothecosis is a rare infection caused by achlorophyllic algae of the
genus Prototheca. The lesions usually occur on exposed areas, related with
trauma, in immunocompromised patients. The most common clinical presentation is a
vesicobullous and ulcerative lesion with pustules and scabs, simulating
bacterial, fungal or herpetic infections or eczema. The diagnosis is determined
by agent identification through histopathology, culture and the carbohydrates
assimilation test. The finding of morula-like spherules is characteristic of
Prototheca sp. Its rarity and non-specific clinical aspect may difficult the
disease diagnosis. We report a case of a diabetic patient, in chronic use of
systemic corticosteroids, that developed a skin lesion after trauma to the right
leg.
PMID- 24346915
TI - Pustular psoriasis of pregnancy (impetigo herpetiformis)--case report.
AB - Impetigo herpetiformis is a rare dermatosis of pregnancy with typical onset
during the last trimester of pregnancy and rapid resolution in the postpartum
period. Clinically and histologically, it is consistent with pustular psoriasis.
This similarity has led some authors to name the disease "the pustular psoriasis
of pregnancy". We report the case of a patient who developed impetigo
herpetiformis in two successive pregnancies.
PMID- 24346916
TI - Epidermodysplasia verruciformis in a young man with HIV since birth--case report.
AB - Epidermodysplasia Verruciformis is a genodermatosis characterized by
susceptibility to infection by specific HPV types (HPV 3/10 and beta-HPVs). It is
considered to be the first model in human carcinogenesis induced by HPV. In this
report we present a rare case of Epidermodysplasia Verruciformis associated with
vertical transmission of HIV. Although most patients with HIV present infections
by HPV virus, the frequency of Epidermodysplasia Verruciformis is no greater in
patients with HIV because in EV there is a deficiency of specific cellular
immunity to infection by some types of HPV, called HPV-related Epidermodysplasia
Verruciformis.
PMID- 24346917
TI - Sacroiliitis after use of oral isotretinoin--association with acne fulminans or
adverse effect?
AB - Acne fulminans is a rare and severe form of acne that may evolve from acne
vulgaris, especially in male adolescents, or occur as an adverse effect of oral
isotretinoin. Arthritis is a serious clinical manifestation when the
musculoskeletal system is compromised by AF and has been reported as a rare
adverse effect of isotretinoin. Involvement of the sacroiliac joints occurs in
21% of acne fulminans cases. We present the case of a 18-year-old male patient in
whom acne fulminans evolved from acne vulgaris grade IV and after inflammation
resolution started treatment with oral isotretinoin. Within a 30-day period of
retinoid treatment he presented with back pain followed by rapid, progressive
inability to deambulate.
PMID- 24346918
TI - Systemic sarcoidosis induced by etanercept: first Brazilian case report.
AB - The antagonists of tumor necrosis factor alpha (TNF-alpha) are increasingly being
used in the treatment of inflammatory and autoimmune diseases. Several adverse
effects of these drugs have been reported, including the paradoxical development
of sarcoidosis, especially with the use of etanercept. We present the first
Brazilian case report of systemic sarcoidosis induced by etanercept and a
literature review.
PMID- 24346919
TI - Classic Kaposi's sarcoma treated with elastic stockings and outpatient follow-up
of a 90-year-old patient.
AB - Kaposi's sarcoma is a multifactorial angioproliferative disorder. The herpes
virus 8 human contributes to its pathogenesis, but it is uncertain whether these
lesions are only reactive hyperplasia to the virus or neoplasia. Four clinical
types are described: classic, endemic, iatrogenic and HIV-associated. Classic
Kaposi's sarcoma has no standard staging or treatment protocols. Some studies
have shown the use of compression stockings in the treatment of lymphedema
associated with Kaposi's sarcoma. We report the case of a 90 year-old patient
with classic Kaposi's sarcoma treated with compression stockings who showed a
satisfactory response.
PMID- 24346920
TI - Birt-Hogg-Dube syndrome.
AB - A 45-year-old woman with a history of renal carcinoma was observed for facial,
cervical and truncal flesh-colored papules. Relatives had similar skin findings
and a brother had repeated episodes of pneumothorax. The computerized tomography
scan revealed multiple cysts on both lungs. A skin biopsy revealed a
perifollicular fibroma. The clinical diagnosis of Birt-Hogg-Dube syndrome (BHDS)
was corroborated by identification of a novel frameshift c.573delGAinsT
(p.G191fsX31) mutation in heterozygosity on exon 6 of the folliculin gene. The
presence of multiple and typical benign hair follicle tumors highlights the role
of the dermatologist in the diagnosis of this rare genodermatosis that is
associated with an increased risk of renal cell cancer and pulmonary cysts,
warranting personal and familial follow-up and counseling.
PMID- 24346921
TI - Vohwinkel syndrome, ichthyosiform variant--by Camisa--case report.
AB - Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare autosomal
dominant palmoplantar keratosis, which manifests in infants and becomes more
evident in adulthood. Its mode of inheritance is autosomal dominant with mutation
in loricrin and Connexin 26 genes. Patients with this mutation present
hyperkeratosis of the palms and soles, constricting bands of the digits, usually
on the fifth, and starfish-shaped hyperkeratosis on the dorsal aspects of the
hands and feet. The disease mostly occurs in white women, where constricting
fibrous bands appear on the digits and can lead to progressive strangulation and
auto-amputation (pseudo-ain-hum).The authors report a rare case of a patient with
a clinical ichthyosiform variant of Vohwinkel syndrome.
PMID- 24346922
TI - Bazex syndrome.
AB - Acrokeratosis Paraneoplastica or Bazex syndrome is a dermatologic manifestation
usually associated with the diagnosis of squamous cell carcinoma of the upper
aerodigestive tract. We report a case with exuberant clinical manifestations,
exemplifying the typical cutaneous lesions in this rare syndrome, in a patient
with squamous cell carcinoma of the esophagus.
PMID- 24346923
TI - Sporadic Kindler syndrome with a novel mutation.
AB - We report the case of a 28-year-old woman with Kindler syndrome, a rare form of
epidermolysis bullosa. Clinically, since childhood, she had widespread pigmentary
changes in her skin as well as photosensitivity and fragility of the skin and
mucous membranes. The mucosal involvement led to an erosive stomatitis as well as
esophageal, anal and vaginal stenoses, requiring surgical intervention. The
diagnosis of Kindler syndrome was confirmed by DNA sequencing with compound
heterozygosity for a nonsense/frameshift combination of mutations (p.Arg110X;
p.Ala289GlyfsX7) in the FERMT1 gene.
PMID- 24346924
TI - Allogeneic hematopoietic stem cell transplantation in mycosis fungoides.
AB - Mycosis Fungoides is typically an indolent disease in early stages. However,
approximately 30% of patients have advanced staged disease at presentation and
20% will develop it at some time. These patients have a poorer prognosis with a
median survival of 2-4 years. The only curative option for mycosis fungoides may
be hematopoietic allogeneic stem cell transplantation. We report the case of a
patient with mycosis fungoides in an advanced stage (IIB), refractory to
treatment options. She underwent allogeneic hematopoietic stem-cell
transplantation (allo-HSCT). The patient remains in complete remission nineteen
months after allo-HSCT. Allogeneic transplantation can alter the natural history
of mycosis fungoides and should be considered in patients who have refractory
disease or short-lived responses with standard therapies.
PMID- 24346925
TI - Propranolol for treatment of infantile hemangiomas.
AB - Infantile hemangioma is the most common vascular tumor in early childhood.
Propranolol has been successfully used recently in a limited number of children
with Infantile hemangioma. We present 6 cases of Infantile hemangioma, at a
single dermatological center, which responded to oral propranolol with good
results.
PMID- 24346926
TI - Use of the bilobed flap in the pubic region after tumoral lesion excision.
AB - Reconstruction of surgical defects in the pubic region is a challenge to any
surgeon. Our goal was to demonstrate the use of the bilobed flap to reconstruct
the pubic region skin after the excision of a recurrent HPV lesion, resistant to
conventional treatments. In spite of its classical use in nasal reconstructions,
the bilobed flap has applications in extranasal defects, with excellent
functional and aesthetic results.
PMID- 24346927
TI - Livedoid vasculopathy associated with peripheral neuropathy: a report of two
cases.
AB - Livedoid vasculopathy (LV) is a chronic and recurrent disease consisting of
livedo reticularis and symmetric ulcerations, primarily located on the lower
extremities, which heal slowly and leave an atrophic white scar ("atrophie
blanche"). Neurological involvment is rare and presumed to be secondary to the
ischemia from vascular thrombosis of the vasa nervorum. Laboratory evaluation is
needed to exclude secondary causes such as hyper-coagulable states, autoimmune
disorders and neoplasms. We present two patients with a rare association of
peripheral neuropathy and LV, thereby highlighting the importance of a
multidisciplinary approach to reach the correct diagnosis.
PMID- 24346928
TI - A secure and efficient authentication and key agreement scheme based on ECC for
telecare medicine information systems.
AB - In the field of the Telecare Medicine Information System, recent researches have
focused on consummating more convenient and secure healthcare delivery services
for patients. In order to protect the sensitive information, various attempts
such as access control have been proposed to safeguard patients' privacy in this
system. However, these schemes suffered from some certain security defects and
had costly consumption, which were not suitable for the telecare medicine
information system. In this paper, based on the elliptic curve cryptography, we
propose a secure and efficient two-factor mutual authentication and key agreement
scheme to reduce the computational cost. Such a scheme enables to provide the
patient anonymity by employing the dynamic identity. Compared with other related
protocols, the security analysis and performance evaluation show that our scheme
overcomes some well-known attacks and has a better performance in the telecare
medicine information system.
PMID- 24346929
TI - Smartphones and health promotion: a review of the evidence.
AB - Communication via mobile phones has become an essential tool for health
professionals. The latest generation of smartphones is comparable to computers,
allowing the development of new applications in health field. This paper aims to
describe the use of smartphones by health professionals and patients in the field
of health promotion. We conducted a bibliographic search through Pubmed. Then,
research results were analyzed critically in order to select the best experiences
available. All searches were carried out on November 2012 and were not limited by
date. Each item from the initial search was reviewed independently by members of
the project team. Initial search returned 472 items with PubMed. After the
removal of duplicates, 406 items were reviewed by all the members of the project
team and 21 articles were identified as specifically centered on health
promotion. In the nutrition field there are applications that allow to count
calories and keep a food diary or more specific platforms for people with food
allergies, while about physical activity many applications suggest exercises with
measurement of sports statistics. Some applications deal with lifestyles
suggestions and tips. Finally, some positive experiences are reported in the
prevention of falls in elderly and of sexually-transmitted diseases. Smartphones
are transforming the ways of communication but the lack of monitoring of
contents, the digital divide, the confidentiality of data, the exclusion of the
health professional from the management of patient, are the main risks related to
their use.
PMID- 24346930
TI - A collaboration tool based on SNOCAP-HET.
AB - Health enabling technologies and ambient assisted living are important fields in
biomedical informatics. In this context, a huge variety of analysis methods are
applied. Neither is a suitable structuring of these methods available, nor is an
aid known for selecting appropriate methods for a given set of data specifying a
context and a problem. The goal of the present paper is to present a prototype of
a semantic collaboration tool which is based on the Systematic Nomenclature for
Contexts, Analysis Methods and Problems in Health-Enabling Technologies (SNOCAP
HET). This tool can be seen as a first step towards an assistance system for
decision support within SNOCAP-HET. We present aspects of the selection and
modeling process of our tool and discuss its benefits and appealing tasks for
further research. Moreover we present a number of already planned and some
unspecified upcoming steps which should optimize SNOCAP-HET in the future.
PMID- 24346931
TI - Smart environment as a service: three factor cloud based user authentication for
telecare medical information system.
AB - The Telecare Medical Information System (TMIS) provides a set of different
medical services to the patient and medical practitioner. The patients and
medical practitioners can easily connect to the services remotely from their own
premises. There are several studies carried out to enhance and authenticate
smartcard-based remote user authentication protocols for TMIS system. In this
article, we propose a set of enhanced and authentic Three Factor (3FA) remote
user authentication protocols utilizing a smartphone capability over a dynamic
Cloud Computing (CC) environment. A user can access the TMIS services presented
in the form of CC services using his smart device e.g. smartphone. Our framework
transforms a smartphone to act as a unique and only identity required to access
the TMIS system remotely. Methods, Protocols and Authentication techniques are
proposed followed by security analysis and a performance analysis with the two
recent authentication protocols proposed for the healthcare TMIS system.
PMID- 24346932
TI - Systems, technology and the critical need for rigorous evaluation.
PMID- 24346934
TI - 50 years ago ...
PMID- 24346936
TI - Genomic imprinting--the struggle of the genders at the molecular level.
AB - Genomic imprinting, the parent of origin-dependent expression of genes, has been
discovered as a fascinating example of the control of gene expression by
epigenetic processes in the human body. It affects about 100 genes, which are
often involved in growth and development. In this Review, we discuss the
mechanisms leading to the generation of gender-specific imprints in form of DNA
methylation marks, their preservation during growth and development of the
organism, and the processes that translate parental methylation marks into
monoallelic gene expression. We discuss the gender-specific dimorphic nature of
imprints from an evolutionary point of view and present the prevalent model that
molecular imprinting mediates a conflict of interest between the parents that
occurs in viviparous animals. Finally, we summarize the relevance of parental
imprinting for human health.
PMID- 24346937
TI - Unusual 14-electron fragments [Pd(eta(3) -Bi3-x Pbx )]((x+1)-) as pseudo lead
atoms in closo-[Pd@Pd2 Pb10 Bi6 ](4-).
AB - How to simplify a complex thing: A salt of the heaviest intermetalloid cluster
known to date, [K([2.2.2]crypt)]4 [Pd@Pd2 Pb10 Bi6 ]?2 en, resulted from a
reaction of [Pd(PPh3 )4 ] with [K([2.2.2]crypt)]2 (Pb2 Bi2 )?2 en in ethane-1,2
diamine (en). The electron number of the ternary intermetalloid anion accords
with Wade-Mingos rules, as the [Pd(eta(3) -Bi3-x Pbx )]((x+1)-) (x=0, 1) 14
electron fragments formed in situ are isolobal with Pb atoms.
PMID- 24346938
TI - Synthesis and biological evaluation of paleo-soraphens.
AB - Synthesis can provide molecules such as paleo-soraphens A and B that are
genetically encoded but not obtained from the natural source. Although it is
unclear whether this is part of an evolutionary process or the consequence of the
chemical synthesis, the biological evaluation of these genetically encoded
natural products can shed light on how natural products are structurally
optimized with respect to their biological profile.
PMID- 24346939
TI - Asymmetric synthesis of pyrroloindolones by N-heterocyclic carbene catalyzed
[2+3] annulation of alpha-chloroaldehydes with nitrovinylindoles.
AB - NHC-enolate plus 3: N-heterocyclic carbenes (NHCs) serve as organocatalysts for
the [2+3] annulation of nitrovinylindoles with alpha-chloroaldehydes via an
intermediate azolium enolate. The method provides trans-disubstituted
pyrroloindolones with good yields and excellent diastereo- and
enantioselectivities. Further transformations lead to tetracyclic pyrrolo[1,2
a]indoles with potential psychotropic and other bioactivities.
PMID- 24346940
TI - Three-dimensional N-doped graphene hydrogel/NiCo double hydroxide
electrocatalysts for highly efficient oxygen evolution.
AB - A highly hydrated structure was fabricated for catalyzing the oxygen evolution
reaction (OER), which demonstrated significantly enhanced catalytic activity,
favorable kinetics, and strong durability. The enhanced performance is correlated
with the dual-active-site mechanism, and high hydrophilicity of the electrode can
dramatically expedite the process of water oxidation into molecular oxygen.
PMID- 24346941
TI - Controllable optical activity of gold nanorod and chiral quantum dot assemblies.
AB - The optical coupling between Au nanorods (Au NRs) and chiral quantum dots (QDs)
in assemblies is investigated by both experiment and theoretical calculations.
The coupled optical activity in the visible-light region can be manipulated by
changing either the aspect ratio of Au NRs or the size of QDs (left).
PMID- 24346942
TI - [2+2+2] Cycloadditions of siloxy alkynes with 1,2-diazines: from reaction
discovery to identification of an antiglycolytic chemotype.
AB - Cycloaddition uncovered: The title reaction produces novel polycyclic compounds
with high efficiency and excellent diastereoselectivity under mild reaction
conditions. A small-molecule library, synthesized using this reaction, yielded a
novel chemotype which inhibited glycolytic ATP production by blocking glucose
uptake in CHO-K1 cells. DMF=N,N-dimethylformamide, Tf=trifluoromethanesulfonyl,
TIPS=triisopropylsilyl.
PMID- 24346943
TI - Low-overpotential water oxidation by a surface-bound ruthenium-chromophore
ruthenium-catalyst assembly.
AB - When anchored to nanoITO (indium tin oxide), the ruthenium chromophore-catalyst
assembly shown acts as an electrocatalyst for water oxidation, with O2 evolution
occurring at an overpotential of 230 mV in 0.1 M HClO4 . The potential response
of the electrode points to 3 e(-) /2 H(+) oxidized [?Rua (III) ?Rub (IV) ?O](5+)
as the active form of the assembly.
PMID- 24346944
TI - Metal oxychlorides as cathode materials for chloride ion batteries.
AB - A key challenge of chloride ion batteries is to develop cathode materials that
are stable in the electrolytes. Metal oxychlorides are presented as such a
cathode material. The electrochemical performance and the reaction mechanisms of
the BiOCl and FeOCl cathode were investigated. Both cathodes showed reversible
reactions, including a major conversion reaction and a minor intercalation
process, by chloride ion transfer during cycling.
PMID- 24346945
TI - Copper-free asymmetric allylic alkylation of trisubstituted cyclic allyl bromides
using Grignard reagents.
AB - AAA: The asymmetric allylic alkylation (AAA) of trisubstituted cyclic allyl
bromides with Grignard reagents is catalytic (2 mol % of ligand) and
regioselective (SN 2'/SN 2=91:9->100:0). The quaternary carbon centers are formed
with good to high enantioselectivity (e.r.=81.5:19.5->96:4).
PMID- 24346946
TI - Regiospecific N-heteroarylation of amidines for full-color-tunable boron
difluoride dyes with mechanochromic luminescence.
AB - Colors to dye for: Palladium-catalyzed regiospecific N-heteroarylations of
amidines with 2-halo-N-heteroarenes leads to a structurally diverse library of
BF2 /amidine-based complexes. These dyes not only present full-visible-color
solid-state emissions with large Stokes shifts and high fluorescence quantum
yields, but also exhibit a full-color-tunable mechanofluorochromic nature.
PMID- 24346947
TI - Selective and sensitive chromofluorogenic detection of the sulfite anion in water
using hydrophobic hybrid organic-inorganic silica nanoparticles.
AB - In water and wine: Chromofluorogenic detection of the sulfite anion in pure water
was accomplished by using a new hybrid organic-inorganic material that contained
a probe entrapped in hydrophobic biomimetic cavities. This material was used for
the detection of sulfite in red wine.
PMID- 24346948
TI - One-pot tandem approach to spirocyclic oxindoles featuring adjacent spiro
stereocenters.
AB - All in a sequence: An organocatalyzed Morita-Baylis-Hillman
(MBH)/bromination/[3+2] annulation sequence for highly stereoselective syntheses
of bis(spirooxindole)s featuring adjacent spiro-stereocenters is described. The
key step is an unprecedented catalytic asymmetric [3+2] annulation of isatin
derived MBH adducts, containing a tetrasubstituted alkene moiety, with isatins.
PMID- 24346949
TI - Two-dimensional hybrid nanosheets of tungsten disulfide and reduced graphene
oxide as catalysts for enhanced hydrogen evolution.
AB - Composite materials: Tungsten disulfide and WS2 /reduced graphene oxide (WS2
/rGO) nanosheets were fabricated by hydrothermal synthesis using tungsten
chloride, thioacetamide, and graphene oxide (GO) as starting materials. The WS2
nanosheets are efficiently templated on the rGO layer. The WS2 /rGO hybrid
nanosheets show much better electrocatalytic activity for the hydrogen evolution
reaction than WS2 nanosheets alone.
PMID- 24346950
TI - Hydrolytic conversion of a metal-organic polyhedron into a metal-organic
framework.
AB - Twist and release: The metal-organic polyhedron 1 synthesized from 5-(prop-2
ynyloxy)isophthalic acid and Cu(NO3 )2 ? 3 H2 O has a hydrophobic outer surface
and a hydrophilic inner core. In an aqueous medium, the resulting polarity
gradient led to the transformation of 1 into the 2D metal-organic framework 2.
This unique phenomenon enabled the gradual release of entrapped drug molecules.
PMID- 24346951
TI - Graphene oxide as a pathogen-revealing agent: sensing with a digital-like
response.
AB - Turned ON by a pathogen: A highly sensitive pathogen-detection system has been
designed and evaluated for the sensing of E. coli bacteria in diverse matrices.
It employs antibody-quantum dot (Ab-QD) probes and exploits the extraordinary two
dimensional structure and fluorescence-quenching capabilities of graphene oxide.
PMID- 24346952
TI - Breaking pseudo-symmetry in multiantennary complex N-glycans using lanthanide
binding tags and NMR pseudo-contact shifts.
AB - Controlling NMR shifts by lanthanides tagged to a "symmetrical" N-glycan reveals
individual resonances for the residues of the otherwise identical A and B arms.
This method provides a global perspective of conformational features and
interactions in solution.
PMID- 24346953
TI - Natural gas to fuels and chemicals: improved methane aromatization in an oxygen
permeable membrane reactor.
AB - Adding value with membranes: Improved methane aromatization was achieved by using
an oxygen-permeable membrane. The resulting membrane reactor shows a superior
methane conversion and a higher resistance towards catalyst deactivation.
PMID- 24346954
TI - Challenges for a new year.
PMID- 24346955
TI - Influence of experimental conditions on data variability in the liver comet
assay.
AB - The in vivo comet assay has increasingly been used for regulatory genotoxicity
testing in recent years. While it has been demonstrated that the experimental
execution of the assay, for example, electrophoresis or scoring, can have a
strong impact on the results; little is known on how initial steps, that is, from
tissue sampling during necropsy up to slide preparation, can influence the comet
assay results. Therefore, we investigated which of the multitude of steps in
processing the liver for the comet assay are most critical. All together eight
parameters were assessed by using liver samples of untreated animals. In
addition, two of those parameters (temperature and storage time of liver before
embedding into agarose) were further investigated in animals given a single oral
dose of ethyl methanesulfonate at dose levels of 50, 100, and 200 mg/kg, 3 hr
prior to necropsy. The results showed that sample cooling emerged as the
predominant influence factor, whereas variations in other elements of the
procedure (e.g., size of the liver piece sampled, time needed to process the
liver tissue post-mortem, agarose temperature, or time of lysis) seem to be of
little relevance. Storing of liver samples of up to 6 hr under cooled conditions
did not cause an increase in tail intensity. In contrast, storing the tissue at
room temperature, resulted in a considerable time-dependent increase in comet
parameters.
PMID- 24346956
TI - Aripiprazole alone or in combination for acute mania.
AB - BACKGROUND: Bipolar disorder is a mental disorder characterised by episodes of
elevated or irritable mood (manic or hypomanic episodes) and episodes of low mood
and loss of energy (depressive episodes). Drug treatment is the first-line
treatment for acute mania with the initial aim of rapid control of agitation,
aggression and dangerous behaviour. Aripiprazole, an atypical antipsychotic, is
used in the treatment of mania both as monotherapy and combined with other
medicines. The British Association of Psychopharmacology guidelines report that,
in monotherapy placebo-controlled trials, the atypical antipsychotics, including
aripiprazole, have been shown to be effective for acute manic or mixed episodes.
OBJECTIVES: To assess the efficacy and tolerability of aripiprazole alone or in
combination with other antimanic drug treatments, compared with placebo and other
drug treatments, in alleviating acute symptoms of manic or mixed episodes. Other
objectives include reviewing the acceptability of treatment with aripiprazole,
investigating the adverse effects of aripiprazole treatment, and determining
overall mortality rates among those receiving aripiprazole treatment. SEARCH
METHODS: The Cochrane Depression, Anxiety and Neurosis Group's Specialised
Register (CCDANCTR-Studies and CCDANCTR-References) was searched, all years to
31st July 2013. This register contains relevant randomised controlled trials
from: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to
date), and PsycINFO (1967 to date). We also searched Bristol-Myers Squibb
clinical trials register, the World Health Organization (WHO) trials portal
(ICTRP) and ClinicalTrials.gov (to August 2013). SELECTION CRITERIA: Randomised
trials comparing aripiprazole versus placebo or other drugs in the treatment of
acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two review authors
independently extracted data, including adverse effect data, from trial reports
and assessed bias. The drug manufacturer or the trial authors were contacted for
missing data. MAIN RESULTS: Ten studies (3340 participants) were included in the
review. Seven studies compared aripiprazole monotherapy versus placebo (2239
participants); two of these included a third comparison arm-one study used
lithium (485 participants) and the other used haloperidol (480 participants). Two
studies compared aripiprazole as an adjunctive treatment to valproate or lithium
versus placebo as an adjunctive treatment (754 participants), and one study
compared aripiprazole versus haloperidol (347 participants). The overall risk of
bias was unclear. A high dropout rate from most trials (> 20% for each
intervention in eight of the trials) may have affected the estimates of relative
efficacy. Evidence shows that aripiprazole was more effective than placebo in
reducing manic symptoms in adults and children/adolescents at three and four
weeks but not at six weeks (Young Mania Rating Scale (YMRS); mean difference (MD)
at three weeks (random effects) -3.66, 95% confidence interval (CI) -5.82 to
2.05; six studies; N = 1819, moderate quality evidence) - a modest difference.
Aripiprazole was compared with other drug treatments in three studies in adults
lithium was used in one study and haloperidol in two studies. No statistically
significant differences between aripiprazole and other drug treatments in
reducing manic symptoms were noted at three weeks (YMRS MD at three weeks (random
effects) 0.07, 95% CI -1.24 to 1.37; three studies; N = 972, moderate quality
evidence) or at any other time point up to and including 12 weeks. Compared with
placebo, aripiprazole caused more movement disorders, as measured on the Simpson
Angus Scale (SAS), on the Barnes Akathisia Scale (BAS) and by participant
reported akathisia (high quality evidence), with more people requiring treatment
with anticholinergic medication (risk ratios (random effects) 3.28, 95% CI 1.82
to 5.91; two studies; N = 730, high quality evidence). Aripiprazole also led to
more gastrointestinal disturbances (nausea (high quality evidence), and
constipation) and caused more children/adolescents to have a prolactin level that
fell below the lower limit of normal. Significant heterogeneity was present in
the meta-analysis of movement disorders associated with aripiprazole and other
treatments and was most likely due to the different side effect profiles of
lithium and haloperidol. At the three-week time point, meta-analysis was not
possible because of lack of data; however, at 12 weeks, haloperidol resulted in
significantly more movement disorders than aripiprazole, as measured on the SAS,
the BAS and the Abnormal Involuntary Movement Scale (AIMS) and by participant
reported akathisia. By 12 weeks, investigators reported no difference between
aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant
reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; N = 313). AUTHORS'
CONCLUSIONS: Aripiprazole is an effective treatment for mania in a population
that includes adults, children and adolescents, although its use leads to
gastrointestinal disturbances and movement disorders. Comparative trials with
medicines other than haloperidol and lithium are few, so the precise place of
aripiprazole in therapy remains unclear.
PMID- 24346957
TI - Wound drains after incisional hernia repair.
AB - BACKGROUND: Incisional hernias are caused by the failure of the wall of the
abdomen to close after abdominal surgery, leaving a hole through which the
viscera protrude. Incisional hernias are repaired by further surgery. Surgical
drains are frequently inserted during hernia repair with the aim of facilitating
fluid drainage and preventing complications. Traditional teaching has recommended
the use of drains after incisional hernia repair other than for laparoscopic
ventral hernia repair. More than 50% of open mesh repairs of ventral hernias have
drains inserted. However, there is uncertainty as to whether drains are
associated with benefits or harm to the patient. OBJECTIVES: To determine the
effects on wound infection and other outcomes, of inserting a wound drain during
surgery to repair incisional hernias, and, if possible, to determine the
comparative effects of different types of wound drain after incisional hernia
repair. SEARCH METHODS: In November 2013, for this fourth update we searched the
Cochrane Wounds Group Specialised Register, the Cochrane Central Register of
Controlled Trials (CENTRAL), The Cochrane Library, Ovid MEDLINE, Ovid EMBASE, and
EBSCO CINAHL. SELECTION CRITERIA: We considered all randomised trials performed
in adult patients who underwent incisional hernia repair and that compared using
a drain with no drain. We also considered trials that compared different types of
drain. DATA COLLECTION AND ANALYSIS: We extracted data on the characteristics of
the trial, methodological quality of the trials, outcomes (e.g. infection and
other wound complications) from each trial. For each outcome, we calculated the
risk ratio (RR) with 95% confidence intervals (CI) and based on intention-to
treat analysis. MAIN RESULTS: No new trials were identified by the updated
searches. Only one trial was eligible for inclusion in the review with a total of
24 patients randomised to an electrified drain (12 patients) compared with a
corrugated drain (12 patients). There were no statistically significant
differences between the groups for wound infection or in the length of stay in
hospital. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine
whether wound drains after incisional hernia repair are associated with better or
worse outcomes than no drains.
PMID- 24346958
TI - [Pharmacokinetics of intravitreally administered VEGF inhibitors].
AB - BACKGROUND: In addition to topical, periocular and systemic administration,
intravitreal injection has been established in recent years as an additional
standard procedure for ophthalmological drug delivery. This route of
administration is now most frequently used for the therapy of retinal diseases
with vascular endothelial growth factor (VEGF) inhibitors. MATERIAL AND METHODS:
A selective literature review and an analysis of own research data were carried
out. RESULTS: Intravitreal administration achieves high drug concentrations in
the target tissue while minimizing systemic drug exposure. Depending on
properties such as molecular weight and binding capacity to the neonatal Fc
receptor, intravitreally applied VEGF inhibitors can exhibit relevant differences
in intraocular and systemic pharmacokinetics. Moreover, the pharmacokinetics can
be affected by properties of the individual eye, such as ocular volume, vitreous
liquefaction, and prior vitrectomy. CONCLUSIONS: Pharmacokinetics of
intravitreally administered drugs determine both the duration of ocular effect
and the degree of systemic exposure and are thus of clinical relevance with
regard to the reinjection strategy and systemic safety.
PMID- 24346959
TI - A survey of community pharmacists and final-year student pharmacists and their
perception of psychotherapeutic agents.
AB - INTRODUCTION: The World Health Organization has estimated that as many as 450
million people worldwide have mental disorders. More than 44 million people in
the United States have a mental disorder annually, estimating the annual direct
costs of mental illness to exceed US$69 billion. Psychotherapeutic agents are
used to treat mental illnesses and improve quality of life. The purpose of the
study is to assess the knowledge and knowledge perception of community
pharmacists and final-year student pharmacists regarding psychotherapeutic agents
dispensed to their community of patients with mental illness. METHODS: A survey
was distributed to pharmacists and final-year student pharmacists regarding
psychotherapeutic agents. RESULTS: In all, 100 pharmacists and 40 final-year
student pharmacists completed the survey. Upon analysis of surveys returned by
pharmacists, knowledge deficiency was assessed regarding anxiolytics and mood
stabilizers. The analysis of student participant surveys demonstrated knowledge
deficiency regarding antidepressants and anxiolytics. CONCLUSIONS: Final-year
student pharmacists would benefit from the curricular incorporation of courses
and advanced pharmacy practice experiences in Psychiatry. Community pharmacists
caring for customers with psychiatric disorders should take advantage of
continuing education series that highlight updates and new developments regarding
psychotherapeutic agents in order to improve clinical outcomes of patients.
PMID- 24346960
TI - Evidence for sequence scrambling and divergent H/D exchange reactions of doubly
charged isobaric b-type fragment ions.
AB - To date, only a limited number of reports are available on structural variants of
multiply-charged b-fragment ions. We report on observed bimodal gas-phase
hydrogen/deuterium exchange (HDX) reaction kinetics and patterns for substance P
b10(2+) that point to presence of isomeric structures. We also compare HDX
reactions, post-ion mobility/collision-induced dissociation (post-IM/CID), and
sustained off-resonance irradiation-collision induced dissociation (SORI-CID) of
substance P b10(2+) and a cyclic peptide with an identical amino acid (AA)
sequence order to substance P b10. The observed HDX patterns and reaction
kinetics and SORI-CID pattern for the doubly charged head-to-tail cyclized
peptide were different from either of the presumed isomers of substance P
b10(2+), suggesting that b10(2+) may not exist exclusively as a head-to-tail
cyclized structure. Ultra-high mass measurement accuracy was used to assign
identities of the observed SORI-CID fragment ions of substance P b10(2+); over
30% of the observed SORI-CID fragment ions from substance P b10(2+) had
rearranged (scrambled) AA sequences. Moreover, post-IM/CID experiments revealed
the presence of two conformer types for substance P b10(2+), whereas only one
conformer type was observed for the head-to-tail cyclized peptide. We also show
that AA sequence scrambling from CID of doubly-charged b-fragment ions is not
unique to substance P b10(2+).
PMID- 24346961
TI - Quality by design study of the direct analysis in real time mass spectrometry
response.
AB - A mass spectrometry method has been developed using the Quality by Design (QbD)
principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted
to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the
Plackett-Burman design were utilized to evaluate the impact of a number of
factors on the method performance. Multivariate regression and Pareto ranking
analysis indicated that the temperature, determined distance, and sampler speed
were statistically significant (P < 0.05). Furthermore, the Box-Behnken design
combined with response surface analysis was then employed to study the
relationships between these three factors and the quality of the DART-MS
analysis. The analytical design space of DART-MS was thus constructed and its
robustness was validated. In this presented approach, method performance was
mathematically described as a composite desirability function of the critical
quality attributes (CQAs). Two terms of method validation, including analytical
repeatability and method robustness, were carried out at an operating work point.
Finally, the validated method was successfully applied to the pharmaceutical
quality assurance in different manufacturing batches. These results revealed that
the QbD concept was practical in DART-MS method development. Meanwhile, the
determined quality was controlled by the analytical design space. This presented
strategy provided a tutorial to the development of a robust QbD-compliant mass
spectrometry method for industrial quality control.
PMID- 24346962
TI - The alpha-effect and competing mechanisms: the gas-phase reactions of
microsolvated anions with methyl formate.
AB - The enhanced reactivity of alpha-nucleophiles, which contain an electron lone
pair adjacent to the reactive site, has been demonstrated in solution and in the
gas phase and, recently, for the gas-phase S(N)2 reactions of the microsolvated
HOO(-)(H2O) ion with methyl chloride. In the present work, we continue to explore
the significance of microsolvation on the alpha-effect as we compare the gas
phase reactivity of the microsolvated alpha-nucleophile HOO(-)(H2O) with that of
microsolvated normal alkoxy nucleophiles, RO(-)(H2O), in reactions with methyl
formate, where three competing reactions are possible. The results reveal
enhanced reactivity of HOO(-)(H2O) towards methyl formate, and clearly
demonstrate the presence of an overall alpha-effect for the reactions of the
microsolvated alpha-nucleophile. The association of the nucleophiles with a
single water molecule significantly lowers the degree of proton abstraction and
increases the S(N)2 and B(AC)2 reactivity compared with the unsolvated analogs.
HOO(-)(H2O) reacts with methyl formate exclusively via the B(AC)2 channel. While
microsolvation lowers the overall reaction efficiency, it enhances the B(AC)2
reaction efficiency for all anions compared with the unsolvated analogs. This may
be explained by participation of the solvent water molecule in the B(AC)2
reaction in a way that continuously stabilizes the negative charge throughout the
reaction.
PMID- 24346963
TI - Complication rate of neurogenic lower urinary tract dysfunction after spinal cord
injury in Taiwan.
AB - PURPOSE: In view of the limited information on neurogenic lower urinary tract
dysfunction (NLUTD) after spinal cord injury (SCI) in the literature, this study
aimed to investigate the complication rate of NLUTD after SCI and to describe the
clinical management of NLUTD in Taiwan. METHODS: A cross-sectional study was
conducted using the National Health Insurance Research Database of Taiwan from
which patients newly diagnosed with SCI during 2006-2008 were extracted. Records
of diagnosis, prescriptions, and procedures for patients were retrieved to
identify NLUTD cases. The utilization of medical treatments including
pharmacotherapy and procedures such as intermittent and indwelling catheters was
analyzed. RESULTS: A total of 941 eligible SCI patients were identified, with a
mean age of 48.4 (+/-18.5), of which 575 (61.1 %) were male, and 500 (53.1 %)
were with cervical SCI. By the end of 1-year follow-up, 165 (17.5 %) had
developed NLUTD. The characteristics were mostly similar between the NLUTD and
non-NLUTD groups except in age and length of stay (LOS) in hospitals, where
patients with NLUTD were 7.5 years old and had 2.15-month-longer LOS. Over 80 %
of NLUTD patients received urinary catheterization, with approximately half also
receiving pharmacotherapy. CONCLUSIONS: This is the first study using nationwide
datasets to evaluate the overall complication rate of NLUTD associated with SCI,
which is shown to be lower than previously reported. While various treatment
options are available, urinary catheterization is the most common treatment for
NLUTD.
PMID- 24346964
TI - Dynamic hyperpolarized carbon-13 MR metabolic imaging of nonhuman primate brain.
AB - PURPOSE: To investigate hyperpolarized (13) C metabolic imaging methods in the
primate brain that can be translated into future clinical trials for patients
with brain cancer. METHODS: (13) C coils and pulse sequences designed for use in
humans were tested in phantoms. Dynamic (13) C data were obtained from a healthy
cynomolgus monkey brain using the optimized (13) C coils and pulse sequences. The
metabolite kinetics were estimated from two-dimensional localized (13) C dynamic
imaging data from the nonhuman primate brain. RESULTS: Pyruvate and lactate
signal were observed in both the brain and the surrounding tissues with the
maximum signal-to-noise ratio of 218 and 29 for pyruvate and lactate,
respectively. Apparent rate constants for the conversion of pyruvate to lactate
and the ratio of lactate to pyruvate showed a difference between brain and
surrounding tissues. CONCLUSION: The feasibility of using hyperpolarized [1-(13)
C]-pyruvate for assessing in vivo metabolism in a healthy nonhuman primate brain
was demonstrated using a hyperpolarized (13) C imaging experimental setup
designed for studying patients with brain tumors. The kinetics of the metabolite
conversion suggests that this approach may be useful in future studies of human
neuropathology.
PMID- 24346970
TI - Rooftops under snow: Gustave Caillebotte.
PMID- 24346967
TI - Synergistic effect of lung tumor-associated dendritic cell-derived HB-EGF and
CXCL5 on cancer progression.
AB - The interaction between cancer cells and their microenvironment is a paradoxical
cycle that exacerbates cancer progression and results in metastasis. Our study
investigated the mechanism underlying the synergistic enhancement of release of
soluble factors from tumor-associated dendritic cells and its effect on cancer
development. The combination of HB-EGF (heparin-binding EGF-like growth factor)
and CXCL5 (CXCL5/epithelial neutrophil-activating peptide-78) produced a strong
synergistic effect on cancer proliferation, epithelial-mesenchymal transition,
migration and invasion. CXCL5 not only potentiated the classical EGFR pathway and
the AKT and ERK/RSK1/2 signaling pathways but also increased the phosphorylation
of heat shock protein 27 (HSP27), which was slightly increased in A549 cells
treated with either HB-EGF or CXCL5 only. Phosphorylated HSP27 stabilized
sustained AKT activity by direct interaction, leading to enhanced tumor spheroid
formation. Knockdown of HSP27 by shRNA decreased HB-EGF plus CXCL5-mediated tumor
spheroid formation in a three-dimensional culture system, suggesting that
AKT/HSP27 was required for HB-EGF/CXCL5-mediated cancer progression. Inhibiting
RSK also reduces the modulation of c-Fos phosphorylation, Snail upregulation and
cell migration by HB-EGF plus CXCL5, suggesting a synergistic effect of ERK/RSK
and HB-EGF plus CXCL5 on cell migration. In mice, CXCL5 antibody synergistically
enhances the efficiency of the tyrosine kinase inhibitor, gefitinib, without
increasing its toxicity. These results provide evidence that elucidates potential
cross-points between extracellular signals affecting lung cancer progression.
Targeting CXCL5 may provide therapeutic benefits for lung cancer chemotherapy or
immunotherapy.
PMID- 24346971
TI - New law allows organ transplants from deceased HIV-infected donors to HIV
infected recipients.
PMID- 24346972
TI - Clinicians examine advances and challenges in improving quality of end-of-life
care in the ICU.
PMID- 24346973
TI - US registry for sudden death in the young launched by the NIH and CDC.
PMID- 24346985
TI - Rethinking reanalysis.
PMID- 24346986
TI - A piece of my mind. Recognizing pride.
PMID- 24346987
TI - Medical communication companies and continuing medical education: clouding the
sunshine?
PMID- 24346989
TI - The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons
with type 2 diabetes and chronic periodontitis: a randomized clinical trial.
AB - IMPORTANCE: Chronic periodontitis, a destructive inflammatory disorder of the
supporting structures of the teeth, is prevalent in patients with diabetes.
Limited evidence suggests that periodontal therapy may improve glycemic control.
OBJECTIVE: To determine if nonsurgical periodontal treatment reduces levels of
glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to
advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS: The Diabetes
and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter,
randomized clinical trial. Participants had type 2 diabetes, were taking stable
doses of medications, had HbA1c levels between 7% and less than 9%, and untreated
chronic periodontitis. Five hundred fourteen participants were enrolled between
November 2009 and March 2012 from diabetes and dental clinics and communities
affiliated with 5 academic medical centers. INTERVENTIONS: The treatment group (n
= 257) received scaling and root planing plus chlorhexidine oral rinse at
baseline and supportive periodontal therapy at 3 and 6 months. The control group
(n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES:
Difference in change in HbA1c level from baseline between groups at 6 months.
Secondary outcomes included changes in probing pocket depths, clinical attachment
loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis
Model Assessment (HOMA2) score. RESULTS: Enrollment was stopped early because of
futility. At 6 months, mean HbA1c levels in the periodontal therapy group
increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group,
with no significant difference between groups based on a linear regression model
adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P
= .55). Periodontal measures improved in the treatment group compared with the
control group at 6 months, with adjusted between-group differences of 0.28 mm
(95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for
clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing,
and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all).
CONCLUSIONS AND RELEVANCE: Nonsurgical periodontal therapy did not improve
glycemic control in patients with type 2 diabetes and moderate to advanced
chronic periodontitis. These findings do not support the use of nonsurgical
periodontal treatment in patients with diabetes for the purpose of lowering
levels of HbA1c. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00997178.
PMID- 24346990
TI - Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury.
AB - IMPORTANCE: Calcium-channel blockers are metabolized by the cytochrome P450 3A4
(CYP3A4; EC 1.14.13.97) enzyme. Blood concentrations of these drugs may rise to
harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor
of CYP3A4 and azithromycin is not, which makes comparisons between these 2
macrolide antibiotics useful in assessing clinically important drug interactions.
OBJECTIVE: To characterize the risk of acute adverse events following
coprescription of clarithromycin compared with azithromycin in older adults
taking a calcium-channel blocker. DESIGN, SETTING, AND PARTICIPANTS: Population
based retrospective cohort study in Ontario, Canada, from 2003 through 2012 of
older adults (mean age, 76 years) who were newly coprescribed clarithromycin (n =
96,226) or azithromycin (n = 94,083) while taking a calcium-channel blocker
(amlodipine, felodipine, nifedipine, diltiazem, or verapamil). MAIN OUTCOMES AND
MEASURES: Hospitalization with acute kidney injury (primary outcome) and
hospitalization with hypotension and all-cause mortality (secondary outcomes
examined separately). Outcomes were assessed within 30 days of a new
coprescription. RESULTS: There were no differences in measured baseline
characteristics between the clarithromycin and azithromycin groups. Amlodipine
was the most commonly prescribed calcium-channel blocker (more than 50% of
patients). Coprescribing clarithromycin vs azithromycin with a calcium-channel
blocker was associated with a higher risk of hospitalization with acute kidney
injury (420 patients of 96,226 taking clarithromycin [0.44%] vs 208 patients of
94,083 taking azithromycin [0.22%]; absolute risk increase, 0.22% [95% CI, 0.16%
0.27%]; odds ratio [OR], 1.98 [95% CI, 1.68-2.34]). In a subgroup analysis, the
risk was highest with dihydropyridines, particularly nifedipine (OR, 5.33 [95%
CI, 3.39-8.38]; absolute risk increase, 0.63% [95% CI, 0.49%-0.78%]).
Coprescription with clarithromycin was also associated with a higher risk of
hospitalization with hypotension (111 patients of 96,226 taking clarithromycin
[0.12%] vs 68 patients of 94,083 taking azithromycin [0.07%]; absolute risk
increase, 0.04% [95% CI, 0.02%-0.07%]; OR, 1.60 [95% CI, 1.18-2.16]) and all
cause mortality (984 patients of 96,226 taking clarithromycin [1.02%] vs 555
patients of 94,083 taking azithromycin [0.59%]; absolute risk increase, 0.43%
[95% CI, 0.35%-0.51%]; OR, 1.74 [95% CI, 1.57-1.93]). CONCLUSIONS AND RELEVANCE:
Among older adults taking a calcium-channel blocker, concurrent use of
clarithromycin compared with azithromycin was associated with a small but
statistically significant greater 30-day risk of hospitalization with acute
kidney injury. These findings support current safety warnings regarding
concurrent use of CYP3A4 inhibitors and calcium-channel blockers.
PMID- 24346991
TI - Medical communication companies and industry grants.
AB - IMPORTANCE: Medical communication companies (MCCs) are among the most significant
health care stakeholders, supported mainly by drug and device companies. How MCCs
share or protect physicians' personal data requires greater transparency.
OBJECTIVE: To explore the financial relationships between MCCs and drug and
device companies, to describe the characteristics of the large MCCs, and to
explore whether they accurately represent themselves to physicians. DESIGN: We
combined data from the 2010 grant registries of 14 pharmaceutical and device
companies; grouped recipients into categories such as MCCs, academic medical
centers, disease-targeted advocacy organizations, and professional associations;
and created a master list of 19,272 grants. MAIN OUTCOMES AND MEASURES: Determine
the distribution of funds from drug and device companies to various entities and
assess the characteristics of large MCCs. RESULTS: Of the 6493 recipients of more
than $657 million grant awards from drug and device companies, 18 of 363 MCCs
received 26%, academic medical centers received 21%, and disease-targeted
organizations received 15%. For-profit MCCs received 77% of funds (208 of 363).
Among the top 5% of MCCs, 14 of 18 were for-profit. All 18 offered continuing
medical education: 14 offered live and 17 offered online CME courses. All
required physicians to provide personal data. Ten stated that they shared
information with unnamed third parties. Eight stated they did not share
information, but almost all added exceptions. None required explicit physician
consent to their sharing policies. CONCLUSIONS AND RELEVANCE: Medical
communication companies receive substantial support from drug and device
companies. Physicians who interact with MCCs should be aware that all require
personal data from the physician and some share these data with unnamed third
parties.
PMID- 24346992
TI - Annular vesiculobullous eruption in a healthy young man.
PMID- 24346993
TI - Patterns of accelerometer-assessed sedentary behavior in older women.
PMID- 24346994
TI - Suicides among military personnel.
PMID- 24346995
TI - Suicides among military personnel.
PMID- 24346996
TI - Suicides among military personnel.
PMID- 24346997
TI - Suicides among military personnel--reply.
PMID- 24346998
TI - Online identities of physicians.
PMID- 24346999
TI - Online identities of physicians--reply.
PMID- 24347000
TI - Weight loss treatment in obese adults.
PMID- 24347001
TI - Weight loss treatment in obese adults--reply.
PMID- 24347003
TI - The resistance of various nerve-cells to anemia.
PMID- 24347004
TI - JAMA patient page. Blood thinners.
PMID- 24347005
TI - Lymphadenopathy: defining a palpable lymph node.
AB - BACKGROUND: The threshold size required to detect lymphadenopathy via palpation
has never been formally determined. The purpose of this study was to determine
the threshold, sensitivity, and error of node palpation and how this changes with
experience. METHODS: Lymphadenopathy models were created using polyvinyl alcohol
cryogel (PVA-C) to mimic tissue tactility. Node diameter ranged from 0.5 to 4 cm.
Study subjects were medical students, otolaryngology residents, and
otolaryngology consultants. Each subject provided 22 estimates of size. Primary
outcomes were the sensitivity, error (true vs estimated size), and threshold of
palpation. RESULTS: Thirty subjects completed the study. Sensitivity was 60%,
74%, and 86% for students, residents, and consultants, respectively (p < .01).
Error was 0.88 cm, 0.61 cm, and 0.57 cm, respectively (p < .05). Palpation
threshold was 1.32 cm, 0.83 cm, and 0.75 cm, respectively (p < .05). All
participants detected nodes >=2 cm, whereas consultants detected nodes >=1 cm.
CONCLUSION: Experience is associated with decreased palpation threshold and
error, and increased sensitivity. Educational interventions should target nodes
<2 cm.
PMID- 24347006
TI - Long term efficacy of an integrated neurological and vocational rehabilitation
programme for young adults with acquired brain injury.
AB - PURPOSE: To characterise and determine the pre-injury, injury and post-injury
factors associated with vocational outcome 1-9 years post-discharge from a mixed
therapy/educational/vocational rehabilitation (VR) residential programme.
METHODS: 119 clients of working age when they acquired their brain injury and who
had attended the centre between 2002 and 2011 were followed up at least 1 year
post-discharge to determine their vocational outcome as part of an ongoing
review/audit of the service. All clients had had a severe/very severe brain
injury. Clients were classified as having a positive vocational outcome (working
paid/voluntary, full/part-time or undertaking full or part-time vocationally
related education) or negative vocational outcome (undertaking neither work nor
education). RESULTS: Over half of the clients attained a positive vocational
outcome. Length of time since discharge did not differ between those clients with
a positive or negative vocational outcome. Vocational outcome was predicted by
cognitive and motor ability at discharge, and gender. Together these variables
correctly classified the vocational outcome of 76 % of the clients. CONCLUSION:
Clients with severe/very severe brain injury can attain a positive vocational
outcome following intensive neurorehabilitation consisting of traditional
therapies in addition to educational and VR.
PMID- 24347007
TI - The dilemma of refractory epileptic syndromes without structural lesions visible
through conventional MRI. "Sight beyond sight": is it possible to trust what we
cannot see?
PMID- 24347008
TI - Rehabilitation in Parkinson's disease - the challenge to provide early and
ongoing, evidence-based, patient-centred care.
PMID- 24347009
TI - Investigation of magnetic resonance imaging texture analysis as an aid tool for
characterization of refractory epilepsies.
AB - Refractory epilepsies are syndromes for which therapies that employ two or more
antiepileptic drugs, separately or in association, do not result in control of
crisis. Patients may present focal cortical dysplasia or diffuse dysplasia and/or
hippocampal atrophic alterations that may not be detectable by a simple visual
analysis in magnetic resonance imaging. The aim of this study was to evaluate MRI
texture in regions of interest located in the hippocampi, limbic association
cortex and prefrontal cortex of 20 patients with refractory epilepsy and to
compare them with the same areas in 20 healthy individuals, in order to find out
if the texture parameters could be related to the presence of the disease. Of the
11 texture parameters calculated, three indicated the existence of statistically
significant differences between the studied groups. Such findings suggest the
possibility of this technique contributing to studies of refractory epilepsies.
PMID- 24347010
TI - Syncope in patients with drug-resistant epilepsy without apparent cardiovascular
disease.
AB - Epilepsy and syncope are clinical conditions with high prevalence rates in the
general population, and the differential diagnosis between them is difficult.
Objective To assess the frequency of syncope in patients diagnosed with drug
resistant epilepsy (DRE) without appa-rent heart disease, to investigate the
relationship between clinical and electroencephalographic (EEG) changes, and to
verify the role of the inclination test (IT). Method An open, prospective study
from 2004 to 2006, including 35 consecutive patients from the Epilepsy Program of
Hospital Universitario Clementino Fraga Filho who were diagnosed with DRE without
apparent heart disease. Results The frequency of syncope was 25.7% (n=9), with a
significant prevalence in women. Vasovagal syncope (VVS) was the most frequent
diagnosis. Conclusion We found a significant association between syncope and the
presence of autonomic symptoms (p=0.005). The IT plays an important role in the
differential diagnosis of patients with DRE presenting with autonomic symptoms,
regardless of EEG results and brain magnetic resonance imaging (MRI)
abnormalities.
PMID- 24347011
TI - Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs): an intriguing
EEG phenomenon.
AB - SIRPIDs, an acronym for stimulus-induced rhythmic, periodic, or ictal discharges,
were first named in 2004. This is a pattern observed in continuous
electroencephalogram (CEEG) consistently elicited by stimulation in comatose
patients. The pathophysiology of SIRPIDs probably involves dysregulation of
subcortico-cortical projections, particularly thalamocortical circuit, in a
markedly abnormal brain with hyperexci-table cortex. This may explain some
studies found an association of prolonged periodic epileptiform discharges (PEDs)
activity and a higher incidence of concurrent electrographic seizures and
SIRPIDs. An association of SIRPIDs and poor prognosis has already been described.
However, it is not yet possible to assert whether these discharges can cause
neuronal injury or if they are simply a marker of severe brain injury. Objective
of this paper is to review clinical relevance and pathophysiology of SIRPIDs, as
well as its role as a brain response in the critically ill patient.
PMID- 24347012
TI - Quantitative EEG evaluation in patients with acute encephalopathy.
AB - OBJECTIVE: To investigate the use of quantitative EEG (qEEG) in patients with
acute encephalopathies (AEs) and EEG background abnormalities. METHOD: Patients
were divided into favorable outcome (group A, 43 patients) and an unfavorable
outcome (group B, 5 patients). EEGLAB software was used for the qEEG analysis. A
graphic of the spectral power from all channels was generated for each
participant. Statistical comparisons between the groups were performed. RESULTS:
In group A, spectral analysis revealed spectral peaks (theta and alpha frequency
bands) in 84% (38/45) of the patients. In group B, a spectral peak in the delta
frequency range was detected in one patient. The remainder of the patients in
both groups did not present spectral peaks. Statistical analysis showed lower
frequencies recorded from the posterior electrodes in group B patients.
CONCLUSION: qEEG may be useful in the evaluations of patients with AEs by
assisting with the prognostic determination.
PMID- 24347013
TI - Painful temporomandibular disorders, self reported tinnitus, and depression are
highly associated.
AB - OBJECTIVE: The aim of this study was to investigate the association among painful
temporomandibular disorders (TMD), self reported tinnitus, and levels of
depression. METHOD: The sample consisted of 224 individuals with ages ranges from
18 to 76 years. The Research Diagnostic Criteria for Temporomandibular Disorders
Axis I were used to classify TMD and Axis II were used for self reported
tinnitus, and to score the levels of depression. The odds ratio (OR) with 95%
confidence interval (CI) was applied. RESULTS: The presence of painful TMD
without tinnitus was significantly associated with moderate/severe levels of
depression (OR=9.3, 95%; CI: 3.44-25.11). The concomitant presence of painful TMD
and tinnitus self-report increased the magnitude of the association with
moderate/severe levels of depression (OR=16.3, 95%; CI, 6.58-40.51). CONCLUSION:
Painful temporomandibular disorders, high levels of depression, and self reported
tinnitus are deeply associated. However, this association does not imply a causal
relationship.
PMID- 24347014
TI - Muscle strength and executive function as complementary parameters for the
assessment of impairment in Parkinson's disease.
AB - OBJECTIVE: To evaluate the relationship between the quantitative results of
functional and cognitive performance of patients with Parkinson's disease (PD)
and disease severity; and to study the relationship between patients' functional
and cognitive capacity and motor impairment (Unified Parkinson's Disease Rating
Scale - UPDRS III). METHOD: Twenty-nine subjects clinically diagnosed with PD
were classified into three groups according to disease severity using the
modified Hoehn and Yahr Scale (H&Y). They were submitted to functional (Senior
Fitness Test) and neuropsychological tests. Stepwise regression analysis showed a
significant association between H&Y and upper limb strength (r2 =0.30; p=0.005)
and executive function (r2 =0.37; p=0.004). In relation to UPDRS III, there was a
significant association between lower limb strength (r2 =0.27; p=0.010) and
global cognitive status (r2 =0.24; p=0.024). CONCLUSION: The implementation of
simple tests of functional capacity associated with neuropsychological testing
can help to assess disease severity and motor impairment, and can be used to
monitor the response to treatment in PD.
PMID- 24347015
TI - Brazilian cross-cultural translation and adaptation of the "Questionnaire of Life
Quality Specific for Myasthenia Gravis - 15 items".
AB - OBJECTIVE: To translate and to perform the cross-cultural adaptation of the
"Questionnaire of Life Quality Specific for Myasthenia Gravis - 15 items" (MG
QOL15). METHOD: The original English version of the questionnaire was translated
into Portuguese. This version was revised and translated back into English.
Later, both English versions were compared and the divergences were corrected in
the Portuguese text. At a second stage, ten patients with MG followed at the
Neuromuscular Diseases Clinic from the University Hospital, Universidade Federal
de Minas Gerais answered the questionnaire. The authors analyzed the difficulties
and misunderstandings in the application of the questionnaire. RESULTS: The
questions 8, 13 and 15 were considered difficult to understand and were modified
in the final Portuguese version. Most patients (70%) had a total score above 25,
and the statements 3, 8 and 9 showed the highest scores. CONCLUSION: The
Brazilian version of the questionnaire MG-QOL15 seems to be a promising tool for
the assessment of Brazilian patients with MG.
PMID- 24347016
TI - Prevalence of amyotrophic lateral sclerosis in the city of Porto Alegre, in
Southern Brazil.
AB - OBJECTIVE: To determine the prevalence of amyotrophic lateral sclerosis (ALS) in
the city of Porto Alegre, Brazil. METHOD: We conducted an extensive investigation
in clinics and hospitals that provide specialized assistance to these patients,
contacted neurologists and the regional association of people with ALS. RESULTS:
On July 31, 2010, 70 patients were alive and diagnosed with amyotrophic lateral
sclerosis. Considering the population living in the city in the same period
(1,409,351), the estimated prevalence was 5.0 cases per 100,000 people (95% CI,
3.9-6.2), being higher for men (5.2/100,000 95% CI, 3.6-7.2) than for women
(4.8/100,000 95% CI, 3.4-6.5). The prevalence increased with age peaking in the
age group 70-79 years in both genders. CONCLUSION: The prevalence of ALS in the
city of Porto Alegre is similar to that reported in other parts of the world.
PMID- 24347017
TI - Asymmetric optic nerve sheath diameter as an outcome factor following
cranioplasty in patients harboring the 'syndrome of the trephined'.
AB - Decompressive craniectomy (DC) is gaining an increasing role in the neurosurgical
treatment of intractable intracranial hypertension, but not without
complications. A rare complication is the "syndrome of the trephined" (ST). It
occurs when the forces of gravity overwhelm intracranial pressures, leading the
brain to become sunken. OBJECTIVE: To determine the usefulness of asymmetric
optic nerve sheath diameter (ONSD) as an outcome factor after cranioplasty.
METHOD: We followed-up 5 patients submitted to DC and diagnosed with ST. All were
submitted to brain MRI to calculate the ONSD. RESULTS: Only two patients
presented an asymmetric ONSD, being ONSD larger at the site of craniectomy.
Surprisingly these patients had a marked neurological improvement after
cranioplasty. They became independent a week after and statistically earlier than
others. CONCLUSION: It is presumed that the presence of an asymmetric ONSD in
trephined patients is an independent factor of good outcome after cranioplasty.
PMID- 24347018
TI - Referral to rehabilitation in Parkinson's disease: who, when and to what end?
AB - The current state of evidence in non-pharmacological treatments amounts to an
impending paradigm shift in neurology where physicians should be alerted that
some rehabilitation interventions are already supported in current therapeutic
guidelines. This manuscript aims to overview the best scientific data supporting
referral to rehabilitation services in order to help physicians make the best use
of the existing evidence for non-pharmacological treatments in the different
stages of Parkinson's disease.
PMID- 24347019
TI - Babinski's contributions to cerebellar symptomatology: building the basis of the
neurological examination.
AB - Several assumptions about the function of the cerebellum and semiotic signs have
been described over the centuries. Among the long list of famous researchers who
have provided a strong contribution and who have left their names on the highway
of cerebellar research, Joseph Babinski appears as a prominent name. The
description of various forms of cerebellar symptomatology was a major part of
Babinski's work, and clinical terms that he introduced, namely hypermetry ,
diadochokinesia , and asynergy , remain part of contemporary clinical vocabulary.
Babinski studied cerebellar signs in many patients and was able to conduct
longitudinal studies that permitted him to understand the evolution of cerebellar
dysfunction. Babinski contributions to cerebellar symptomatology continue to
influence the most modern theories, including functional and neuropathological
studies.
PMID- 24347020
TI - Unilateral clear hairy tongue sign.
PMID- 24347021
TI - Spinal cord atrophy in spinocerebellar ataxia type 1.
PMID- 24347022
TI - Cardiac evaluation in a patient with epileptic seizures: a value of cardiac
magnetic resonance imaging.
PMID- 24347025
TI - Set shifting in children and adolescents with anorexia nervosa: an exploratory
systematic review and meta-analysis.
AB - OBJECTIVE: Set shifting inefficiencies in adults with anorexia nervosa (AN) are
established, however the neurocognitive profile of children and adolescents with
AN is less clear. This study aimed to provide a review of the literature. METHOD:
Electronic databases were used to search for manuscripts. RESULTS: Meta-analysis
was performed on seven studies using two neuropsychological tests (Trail Making
Task, TMT; Wisconsin Card Sorting Task, WCST). The mean difference in outcome
between AN and healthy control (HC) groups was standardized by calculating
Cohen's d. Meta-analysis of TMT studies showed a nonsignificant negative, pooled
standardized mean difference of -0.005 (95% C.I. -0.416 to 0.406, z = 0.02, p =
.98). WCST studies revealed a nonsignificant pooled effect size of d = 0.196 (95%
C.I. -0.091-0.483, z = 1.34, p = .18). Studies which did not allow for a
calculation of effect size typically showed a nonsignificant, worse performance
by the AN groups. DISCUSSION: The inefficiencies in set shifting that are
apparent in the adult AN literature do not appear to be as pronounced in
children. This may suggest that set shifting difficulties in adult AN are the
result of starvation or indicative of longer duration of illness. Larger studies
are needed to confirm these impressions.
PMID- 24347026
TI - Unveiling benznidazole's mechanism of action through overexpression of DNA repair
proteins in Trypanosoma cruzi.
AB - Benznidazole (BZ) is the most commonly used drug for the treatment of Chagas
disease. Although BZ is known to induce the formation of free radicals and
electrophilic metabolites within the parasite Trypanosoma cruzi, its precise
mechanisms of action are still elusive. Here, we analyzed the survival of T.
cruzi exposed to BZ using genetically modified parasites overexpressing different
DNA repair proteins. Our results indicate that BZ induces oxidation mainly in the
nucleotide pool, as heterologous expression of the nucleotide
pyrophosphohydrolase MutT (but not overexpression of the glycosylase TcOgg1)
increased drug resistance in the parasite. In addition, electron microscopy
indicated that BZ catalyzes the formation of double-stranded breaks in the
parasite, as its genomic DNA undergoes extensive heterochromatin unpacking
following exposure to the drug. Furthermore, the overexpression of proteins
involved in the recombination-mediated DNA repair increased resistance to BZ,
reinforcing the idea that the drug causes double-stranded breaks. Our results
also show that the overexpression of mitochondrial DNA repair proteins increase
parasite survival upon BZ exposure, indicating that the drug induces lesions in
the mitochondrial DNA as well. These findings suggest that BZ preferentially
oxidizes the nucleotide pool, and the extensive incorporation of oxidized
nucleotides during DNA replication leads to potentially lethal double-stranded
DNA breaks in T. cruzi DNA.
PMID- 24347027
TI - Cell proliferation arrest and redox state status as part of different stages
during senescence establishment in mouse fibroblasts.
AB - Senescence phenotype can be achieved by multiple pathways. Most of them involve
the activation of negative cell cycle regulators as well as a shift to an
oxidative status. However, the exact participation of these events in senescence
establishment and maintenance is not completely understood. In this study we
investigated the content of three final cell cycle regulators, as well as the
redox state in some critical points during the pre-senescent and the full
senescent states. Our results highlight the existence of a critical pre-phase in
senescent phenotype establishment, in which cell proliferation stops with the
participation of the cell cycle inhibitors, and a second maintenance stage where
the exacerbated pro-oxidant state inside the cell induces the physiological
decline characteristic in senescent cells.
PMID- 24347028
TI - Photo-crosslinkable PEG-based microribbons for forming 3D macroporous scaffolds
with decoupled niche properties.
AB - PEG-based microribbons are designed and fabricated as building blocks for
constructing a 3D cell niche with independently tunable biochemical, mechanical,
and topographical cues. This platform supports direct cell encapsulation, allows
spatial patterning of biochemical cues, and may provide a valuable tool for
facilitating the analyses of how interactive niche signaling regulates cell fate
in three dimensions.
PMID- 24347029
TI - Angewandte Chemie always new.
PMID- 24347031
TI - Combination versus sequential single agent chemotherapy for metastatic breast
cancer.
AB - BACKGROUND: Combination chemotherapy can cause greater tumour cell kill if the
drug dose is not compromised, while sequential single agent chemotherapy may
allow for greater dose intensity and treatment time, potentially meaning greater
benefit from each single agent. In addition, sequentially using single agents
might cause less toxicity and impairment of quality of life, but it is not known
whether this might compromise survival time. OBJECTIVES: To assess the effect of
combination chemotherapy compared to the same drugs given sequentially in women
with metastatic breast cancer. SEARCH METHODS: We searched the Cochrane Breast
Cancer Group Specialised Register, using the search terms "advanced breast
cancer" and "chemotherapy", MEDLINE and EMBASE on 31 October 2013. The World
Health Organization International Clinical Trials Registry Platform and
ClinicalTrials.gov were also searched (22 March 2012). SELECTION CRITERIA:
Randomised controlled trials of combination chemotherapy compared to the same
drugs used sequentially in women with metastatic breast cancer in the first-,
second- or third-line setting. DATA COLLECTION AND ANALYSIS: Two authors
independently extracted data from published trials. Hazard ratios (HR) were
derived from time-to-event outcomes where possible, and a fixed-effect model was
used for meta-analysis. Response rates were analysed as dichotomous variables
(risk ratios (RR)), and toxicity and quality of life data were extracted where
available. MAIN RESULTS: Twelve trials reporting on nine treatment comparisons
(2317 patients randomised) were identified. The majority of trials (10 trials)
had an unclear or high risk of bias. Time-to-event data were collected for nine
trials for overall survival and eight trials for progression-free survival. All
12 trials reported results for tumour response. In the 12 trials there were 1023
deaths in 2317 women randomised. There was no difference in overall survival,
with an overall HR of 1.04 (95% confidence interval (CI) 0.93 to 1.16; P = 0.45),
and no significant heterogeneity. This result was consistent in the four
subgroups analysed (risk of bias, line of chemotherapy, type of schema of
chemotherapy, and relative dose intensity). In particular, there was no
difference in survival according to the type of schema of chemotherapy, that is
whether chemotherapy was given on disease progression or after a set number of
cycles. In the eight trials that reported progression-free survival, 678 women
progressed out of the 886 women randomised. The combination arm had a higher risk
of progression than the sequential arm (HR 1.16; 95% CI 1.03 to 1.31; P = 0.01)
with no significant heterogeneity. This result was consistent in all subgroups.
Overall tumour response rates were higher in the combination arm (RR 1.13; 95% CI
1.03 to 1.24; P = 0.008) but there was significant heterogeneity for this outcome
across the trials. In the seven trials that reported treatment-related deaths,
there was no significant difference between the two arms, although the CIs were
very wide due to the small number of events (RR 1.53; 95% CI 0.71 to 3.29; P =
0.28). The risk of febrile neutropenia was higher in the combination arm (RR
1.32; 95% CI 1.06 to 1.65; P = 0.01). There was no statistically significant
difference in the risk of neutropenia, nausea and vomiting, or treatment-related
deaths. Overall quality of life showed no difference between the two groups, but
only three trials reported this outcome. AUTHORS' CONCLUSIONS: Sequential single
agent chemotherapy has a positive effect on progression-free survival, whereas
combination chemotherapy has a higher response rate and a higher risk of febrile
neutropenia in metastatic breast cancer. There is no difference in overall
survival time between these treatment strategies, both overall and in the
subgroups analysed. In particular, there was no difference in survival according
to the schema of chemotherapy (giving chemotherapy on disease progression or
after a set number of cycles) or according to the line of chemotherapy (first
line versus second- or third-line). Generally this review supports the
recommendations by international guidelines to use sequential monotherapy unless
there is rapid disease progression.
PMID- 24347030
TI - Cerebral vasospasm after aneurysmal subarachnoid hemorrhage and traumatic brain
injury.
AB - OPINION STATEMENT: Cerebral vasospasm (cVSP) consists of the vasoconstriction of
large and small intracranial vessels which can lead to cerebral hypoperfusion,
and in extreme cases, delayed ischemic deficits with stroke. While most commonly
observed after aneurysmal subarachnoid hemorrhage (aSAH), cVSP can also occur
after traumatic brain injury (TBI) as we have described in detail in this review.
For the past decades, the research attention has focused on cVSP because of its
association with delayed cerebral ischemia, which is the largest contributor of
morbidity and mortality after aSAH. New discoveries in the cVSP pathophysiology
involving multifactorial complex cascades and pathways pose new targets for
therapeutic interventions in the prevention and treatment of cVSP. The goal of
this review is to demonstrate the commonalities and differences in epidemiology
and pathophysiology of both aSAH and TBI-associated cVSP, and highlight the more
recently discovered pathways of cVSP. Finally, the latest cVSP surveillance
methods and treatment options are illustrated.
PMID- 24347032
TI - [Patient-centredness in rehabilitation : an overview on the current state of
research].
AB - This article provides an overall perspective of the concept of patient
centredness in health care. After discussing the social factors that
significantly contribute to this topic, the authors refer to a definition by Mead
and Bower in their understanding of patient-centredness. They distinguished five
facets of patient-centredness, namely the biopsychosocial perspective, seeing the
patient as an individual person, sharing power and responsibility (e.g. shared
decision-making), consideration of the patient-treatment provider relationship
and regarding the treatment provider as a person. The authors discuss why
approaches employing patient-centred care seem particularly well-suited to a
rehabilitation context and emphasize the value and benefit of patient-centred
care. They describe those areas currently engaging the greatest research efforts
in Germany by providing an overview of projects now being conducted in the
funding priority for chronic illnesses and patient orientation. In the final
chapter the authors consider the need for further research as well as the
potential adverse side effects associated with intensified patient-centred care.
PMID- 24347033
TI - Accidental dural puncture, postdural puncture headache, intrathecal catheters,
and epidural blood patch: revisiting the old nemesis.
AB - One of the controversial management options for accidental dural puncture in
pregnant patients is the conversion of labor epidural analgesia to continuous
spinal analgesia by threading the epidural catheter intrathecally. No clear
consensus exists on how to best prevent severe headache from occurring after
accidental dural puncture. To investigate whether the intrathecal placement of an
epidural catheter following accidental dural puncture impacts the incidence of
postdural puncture headache (PDPH) and the subsequent need for an epidural blood
patch in parturients. A retrospective chart review of accidental dural puncture
was performed at Hutzel Women's Hospital in Detroit, MI, USA for the years 2002
2010. Documented cases of accidental dural punctures (N = 238) were distributed
into two groups based on their management: an intrathecal catheter (ITC) group in
which the epidural catheter was inserted intrathecally and a non-intrathecal
catheter (non-ITC) group that received the epidural catheter inserted at
different levels of lumbar interspaces. The incidence of PDPH as well as the
necessity for epidural blood patch was analyzed using two-tailed Fisher's exact
test. In the non-ITC group, 99 (54 %) parturients developed PDPH in comparison to
20 (37 %) in the ITC [odds ratio (OR), 1.98; 95 % confidence interval (CI), 1.06
3.69; P = 0.03]. Fifty-seven (31 %) of 182 patients in the non-ITC group required
an epidural blood patch (EBP) (data for 2 patients of 184 were missing). In
contrast, 7 (13 %) of parturients in the ITC group required an EBP. The incidence
of EBP was calculated in parturients who actually developed headache to be 57 of
99 (57 %) in the non-ITC group versus 7 of 20 (35 %) in the ITC group (OR, 2.52;
95 % CI, 0.92-6.68; P = 0.07). The insertion of an intrathecal catheter following
accidental dural puncture decreases the incidence of PDPH but not the need for
epidural blood patch in parturients.
PMID- 24347034
TI - Plasma ropivacaine concentrations after ultrasound-guided transversus abdominis
plane block for open retropubic prostatectomy.
AB - PURPOSE: Ropivacaine-induced vasoconstriction may affect the early absorption
speed of ropivacaine; however, the effects of dose on pharmacokinetics following
transversus abdominis plane (TAP) block have not been studied. In this study, we
have examined plasma ropivacaine concentrations following TAP block with various
ropivacaine concentrations (0.25, 0.5, and 0.75 %). METHODS: With the approval of
our University ethics committee and informed consent, 39 adult patients
undergoing open retropubic prostatectomy were enrolled. Patients were randomly
assigned to three groups (n = 13 each) receiving TAP block with 20 ml (10 ml each
side) of different concentrations of ropivacaine. To determine plasma
concentrations, blood samples were drawn before and 15, 30, 45, 60, 90, 120, and
180 min after completion of bilateral TAP blocks. Plasma ropivacaine
concentrations were analyzed by gas chromatography with mass spectrometry.
RESULTS: We found that the peak plasma concentrations (C(max)) increased dose
dependently (0.41 +/- 0.14, 0.89 +/- 0.55, and 1.56 +/- 0.50 ug/ml), but the
times to C(max) (23.0 +/- 15.8, 23.1 +/- 14.5, and 20.8 +/- 11.5 min) were not
different between 0.25, 0.5, and 0.75 % ropivacaine doses, respectively. Terminal
elimination half-life (t(1/2)), total body clearance (CL), and distribution
volume (V(d)) were also not different among the three groups. CONCLUSION:
Ropivacaine concentration did not alter pharmacokinetic profile following TAP
blocks.
PMID- 24347035
TI - Perioperative management of factor XI deficiency in a patient undergoing hip
arthroplasty.
AB - Factor XI deficiency, or hemophilia C, is a rare autosomal recessive bleeding
disorder often diagnosed by inappropriate bleeding associated with trauma or a
surgical procedure, and reports of anesthetic management of this disorder are
rare. We experienced an 85-year-old man with femoral neck fracture who was
diagnosed preoperatively with factor XI deficiency based on abnormally long
activated partial thromboplastin time (APTT). He was scheduled for bipolar hip
arthroplasty and was prepared for surgery by transfusion of fresh frozen plasma
(FFP), instead of factor XI concentrates, which are not commercially available in
Japan. Five units of FFP were transfused 6 days before surgery, and 10 units of
FFP with 2 units of red concentrated cells (RCC) were used on the day of surgery.
Transfusion of FFP shortened the APTT to a level sufficient to allow hemostasis,
although not to within the normal range. Although the patient required
transfusion of 2 units of RCC postoperatively, no bleeding complications
occurred. For bipolar hip arthroplasty, transfusion of FFP produced sufficient
hemostasis without the use of tranexamic acid, factor VII preparations, or
desmopressin.
PMID- 24347036
TI - Continued use of 1-in-X Risk communications is a systemic problem.
PMID- 24347037
TI - Pneumococcal glomerulonephritis in a healthy child: a case report and literature
review.
AB - Pneumococcal glomerulonephritis is rarely described in the literature. We report
a four-year-old boy who developed acute glomerulonephritis following pneumococcal
bacteraemia and submandibular lymphadenitis, and review the published literature.
Two weeks after developing acute glomerulonephritis, the patient developed
bronchopneumonia with left pleural effusion. However, by the fourth week of
admission, his renal function had normalised and lung involvement resolved.
PMID- 24347038
TI - Multiple oesophago-respiratory fistulae: sequelae of pulmonary tuberculosis in
retroviral infection.
AB - Pulmonary tuberculosis (PTB) is a common infectious disease worldwide. However,
mediastinal tuberculous lymphadenitis complicated by oesophageal involvement and
oesophago-respiratory fistula is now uncommon due to improved anti-tuberculous
regimes and better general awareness. The overall incidence of acquired oesophago
respiratory fistula due to infection is low, and therefore, the lesion is not
often a frontrunner in differential diagnosis. Still, tuberculous oesophago
respiratory fistulae can potentially occur in patients with retroviral disease,
as they tend to have atypical and more virulent manifestations. In this study, we
report the case of multiple oesophago-respiratory fistulae in a patient with PTB
and retroviral disease, and highlight the computed tomography features of these
lesions as an atypical presentation of PTB in retroviral disease. Clinicians
should suspect oesophago-respiratory fistulae if patients present with Ono's
sign, and remain particularly vigilant for patients with underlying PTB and
retroviral disease, as early diagnosis and treatment could help to reduce
mortality.
PMID- 24347039
TI - Hepatic tuberculosis: a rare cause of fluorodeoxyglucose hepatic superscan with
background suppression on positron emission tomography.
AB - Fluorodeoxyglucose (FDG) hepatic superscan refers to the diffuse intense uptake
of 18F-FDG in the liver on positron emission tomography (PET), with reduced
physiological activity in the brain and heart. The common causes include lymphoma
and metastasis. In this case report, we describe the imaging features of
tuberculosis as a rare cause of FDG hepatic superscan. PET imaging may be the
only clue to a diagnosis of hepatic tuberculosis, as other imaging modalities may
demonstrate only nonspecific hepatomegaly. It is important to consider this
entity in the differential diagnosis of patients presenting with FDG hepatic
superscan and proceed with liver biopsy for a definitive diagnosis.
PMID- 24347040
TI - Convex gradient optimization for increased spatiotemporal resolution and improved
accuracy in phase contrast MRI.
AB - PURPOSE: To evaluate convex gradient optimization (CVX) for increased
spatiotemporal resolution and improved accuracy for phase-contrast MRI (PC-MRI).
METHODS: A conventional flow-compensated and flow-encoded (FCFE) PC-MRI sequence
was compared with a CVX PC-MRI sequence using numerical simulations, flow phantom
experiments, and in vivo experiments. Flow measurements within the ascending
aorta, main pulmonary artery, and right/left pulmonary arteries of normal
volunteers (N = 10) were acquired at 3T and analyzed using a conventional FCFE
sequence and a CVX sequence with either higher spatial resolution or higher
temporal resolution. All sequences mitigated chemical shift-induced phase errors
and used equivalent breath-hold durations. RESULTS: Chemical shift-optimized PC
MRI has increased sequence efficiency when using CVX, which can provide either
higher spatial or higher temporal resolution compared with conventional FCFE PC
MRI. Numerical simulations, flow phantom experiments, and in vivo experiments
indicate that CVX measurements of total flow and peak velocity are increased and
more accurate when compared with FCFE. CONCLUSION: CVX PC-MRI increases sequence
efficiency while reducing chemical shift-induced phase errors. This can be used
to provide either higher spatial or higher temporal resolution than conventional
chemical shift-mitigated PC-MRI methods to provide more accurate measurements of
blood flow and peak velocity.
PMID- 24347041
TI - Fragment N2, a caspase-3-generated RasGAP fragment, inhibits breast cancer
metastatic progression.
AB - The p120 RasGAP protein negatively regulates Ras via its GAP domain. RasGAP
carries several other domains that modulate several signaling molecules such as
Rho. RasGAP is also a caspase-3 substrate. One of the caspase-3-generated RasGAP
fragments, corresponding to amino acids 158-455 and called fragment N2, was
previously reported to specifically sensitize cancer cells to death induced by
various anticancer agents. Here, we show that fragment N2 inhibits migration in
vitro and that it impairs metastatic progression of breast cancer to the lung.
Hence, stress-activated caspase-3 might contribute to the suppression of
metastasis through the generation of fragment N2. These results indicate that the
activity borne by fragment N2 has a potential therapeutic relevance to counteract
the metastatic process.
PMID- 24347042
TI - Characterizing ensemble statistics: mean size is represented across multiple
frames of reference.
AB - The visual system represents the overall statistical, not individual, properties
of sets. Here we tested the spatial nature of ensemble statistics. We used a mean
size adaptation paradigm (Corbett et al. in Visual Cognition, 20, 211-231, 2012)
to examine whether average size is encoded in multiple reference frames. We
adapted observers to patches of small- and large-sized dots in opposite regions
of the display (left/right or top/bottom) and then tested their perceptions of
the sizes of single test dots presented in regions that corresponded to
retinotopic, spatiotopic, and hemispheric coordinates within the adapting
displays. We observed retinotopic, spatiotopic, and hemispheric adaptation
aftereffects, such that participants perceived a test dot as being larger when it
was presented in the area adapted to the patch of small dots than when it was
presented in the area adapted to large dots. This aftereffect also transferred
between eyes. Our results demonstrate that mean size is represented across
multiple spatial frames of reference, supporting the proposal that ensemble
statistics play a fundamental role in maintaining perceptual stability.
PMID- 24347043
TI - Evidence behind FDA alerts for drugs with adverse cardiovascular effects:
implications for clinical practice.
AB - The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety
Communications and Drug Alerts notifying health care practitioners and the
general public of important information regarding drug therapies following FDA
approval. These alerts can result in both positive and negative effects on
patient care. Most clinical trials are not designed to detect long-term safety
end points, and postmarketing surveillance along with patient reported events are
often instrumental in signaling the potential harmful effect of a drug. Recently,
many cardiovascular (CV) safety announcements have been released for FDA-approved
drugs. Because a premature warning could discourage a much needed treatment or
prompt a sudden discontinuation, it is essential to evaluate the evidence
supporting these FDA alerts to provide effective patient care and to avoid
unwarranted changes in therapy. Conversely, paying attention to these warnings in
cases involving high-risk patients can prevent adverse effects and litigation.
This article reviews the evidence behind recent FDA alerts for drugs with adverse
CV effects and discusses the clinical practice implications.
PMID- 24347044
TI - Distinct patterns of global promoter methylation in early stage chronic
lymphocytic leukemia.
AB - Genomic and epigenomic studies of chronic lymphocytic leukemia (CLL) are
reshaping our understanding of the disease and have provided new perspectives for
a more individualized diagnosis and new potential therapeutic targets. In this
study, the global promoter methylation profile was determined in highly purified
B-cells from 37 (Binet stage A) CLL patients, using high-resolution methylation
microarrays (27,578 CpG). Overall, the methylation pattern correlated with the
major biological (ZAP-70 and CD38), and molecular (IGHV mutation) markers,
distinguishing CLL cases according to IGHV mutational status. Cell adhesion
molecules were enriched in the signature of unmutated (UM) versus mutated (M-)
CLL. Moreover, in M-CLL CpG hyper-methylation in three genes, including SPG20,
was significantly anti-correlated with the corresponding gene expression level.
Finally, the correlation between the methylation pattern and clinical parameters
was investigated. Notably, out of 42 methyl-probes that were significantly
associated with progression free survival (PFS), hyper-methylation of SPG20 was
also positively associated with PFS. These data support the notion that
epigenetic changes have clinical impact in CLL and may contribute to the
identification of novel candidate disease-associated genes potentially useful to
predict the clinical outcome of early stage CLL patients.
PMID- 24347045
TI - Isolation and phylogenetic analysis of an orf virus from sheep in Makhdoom,
India.
AB - Orf (contagious ecthyma) is an exanthematic disease caused by a parapoxvirus and
occurs primarily in sheep and goats with zoonotic implications. In the present
investigation, an orf outbreak in the Muzzaffarnagari sheep flock at the Central
Institute for Research on Goats (CIRG), Makhdoom, Mathura, Uttar Pradesh, India,
was investigated. Primary goat testes cell culture was used for isolation of the
orf virus (ORFV) for the first time. The identity of the virus was confirmed by
amplification and sequence analysis of the major envelope glycoprotein (B2L) gene
and named ORFV/sheep/India/2012/CIRG. On phylogenetic analysis of B2L protein
gene, it clustered with the ORFV strains from China suggesting distinct ORFV
strains are circulating in India. On comparison of nucleotide and deduced amino
acid sequence analysis (n = 63), a unique 126S residue was observed in
ORFV/sheep/India/2012/CIRG. On further sequence analysis (B2L) of different ORFV
strains (n = 63), some conserved amino acid residues were identified as host
specific (sheep, human, camel, takin, and musk ox) and have been summarized.
PMID- 24347046
TI - Risk factors for revision within 10 years of total knee arthroplasty.
AB - BACKGROUND: An in-depth understanding of risk factors for revision TKA is needed
to minimize the burden of revision surgery. Previous studies indicate that
hospital and community characteristics may influence outcomes after TKA, but a
detailed investigation in a diverse population is warranted to identify
opportunities for quality improvement. QUESTIONS/PURPOSES: We asked: (1) What is
the frequency of revision TKA within 10 years of primary arthroplasty? (2) Which
patient demographic factors are associated with revision within 10 years of TKA?
(3) Which community and institutional characteristics are associated with
revision within 10 years of TKA? METHODS: We identified 301,955 patients who
underwent primary TKAs in New York or California from 1997 to 2005 from statewide
databases. Identifier codes were used to determine whether they underwent
revision TKA. Patient, community, and hospital characteristics were analyzed
using multivariable regression modeling to determine predictors for revision.
RESULTS: The frequency of revision was 4.0% at 5 years after the index
arthroplasty and 8.9% at 9-years. Patients between 50 and 75 years old had a
lower risk of revision than patients younger than 50 years (hazard ratio [HR],
0.47; 95% CI, 0.44, 0.50). Black patients were at increased risk for needing
revision surgery (HR, 1.39; 95% CI, 1.29, 1.49) after adjustment for insurance
type, poverty level, and education. Women (HR, 0.82; 95% CI, 0.79, 0.86) and
Medicare recipients (HR, 0.82; 95% CI, 0.79, 0.86) were less likely to undergo
revision surgery, whereas those from the most educated (HR, 1.09; 95% CI, 1.02,
1.16) and the poorest communities (HR, 1.08; 95% CI, 1.01, 1.15) had modest
increases in risk of revision. Mid-volume hospitals (200-400 annual cases) had a
reduction of early revision (HR, 0.91; 95% CI, 0.83, 0.99) compared with those
performing less than 200 cases annually, whereas higher-volume hospitals (greater
than 400 cases) showed little effect compared with low-volume hospitals.
CONCLUSIONS: Patient, community, and institutional characteristics affect the
risk for revision within 10 years of index TKA. These data can be used to develop
process improvement and implant surveillance strategies among high-risk patients.
LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors
for a complete description of levels of evidence.
PMID- 24347047
TI - Effects of silver nanoparticles on oxidative DNA damage-repair as a function of
p38 MAPK status: a comparative approach using human Jurkat T cells and the
nematode Caenorhabditis elegans.
AB - The large-scale use of silver nanoparticles (AgNPs) has raised concerns over
potential impacts on the environment and human health. We previously reported
that AgNP exposure causes an increase in reactive oxygen species, DNA damage, and
induction of p38 MAPK and PMK-1 in Jurkat T cells and in Caenorhabditis elegans.
To elucidate the underlying mechanisms of AgNP toxicity, here we evaluate the
effects of AgNPs on oxidative DNA damage-repair (in human and C. elegans DNA
glycosylases hOGG1, hNTH1, NTH-1, and 8-oxo-GTPases-hMTH1, NDX-4) and explore the
role of p38 MAPK and PMK-1 in this process. Our comparative approach examined
viability, gene expression, and enzyme activities in wild type (WT) and p38 MAPK
knock-down (KD) Jurkat T cells (in vitro) and in WT and pmk-1 loss-of-function
mutant strains of C. elegans (in vivo). The results suggest that p38 MAPK/PMK-1
plays protective role against AgNP-mediated toxicity, reduced viability and
greater accumulation of 8OHdG was observed in AgNP-treated KD cells, and in pmk-1
mutant worms compared with their WT counterparts, respectively. Furthermore, dose
dependent alterations in hOGG1, hMTH1, and NDX-4 expression and enzyme activity,
and survival in ndx-4 mutant worms occurred following AgNP exposure.
Interestingly, the absence or depletion of p38 MAPK/PMK-1 caused impaired and
additive effects in AgNP-induced ndx-4(ok1003); pmk-1(RNAi) mutant survival, and
hOGG1 and NDX-4 expression and enzyme activity, which may lead to higher
accumulation of 8OHdG. Together, the results indicate that p38 MAPK/PMK-1 plays
an important protective role in AgNP-induced oxidative DNA damage-repair which is
conserved from C. elegans to humans.
PMID- 24347048
TI - Effect of acute hexavalent chromium exposure on pituitary-thyroid axis of a
freshwater fish, Channa punctatus (Bloch).
AB - Acute exposure to hexavalent chromium (10 mg L(-1) , 20 mg L(-1) , and 40 mg L(
1) potassium dichromate for 96 h) dose-dependently affected the pituitary-thyroid
axis of teleost, Channa punctatus. Significant hypertrophy of the thyroid
follicle was observed in 20 mg L(-1) and 40 mg L(-1) groups; the follicular
epithelium was however hypertrophied only in 40 mg L(-1) group. The colloid
depletion in the lumen of thyroid follicle was evident in 20 mg L(-1) and 40 mg
L(-1) groups. Serum thyroid hormones (thyroxine/T4 and triiodothyronine/T3) level
increased significantly at both the higher doses. Increased immunointensity and
significant hypertrophy of the pituitary thyrotrophs (anti TSHbeta-immunoreactive
cells) was observed in both 20 mg L(-1) and 40 mg L(-1) chromium-exposed fish.
The increased thyroid hormones secretion observed in this study might be an
adaptive response of the pituitary-thyroid axis under acute chromium-induced
stress condition to maintain homeostasis. The long-term Cr(VI) exposures,
however, may lead to attenuation/exhaustion of the pituitary-thyroid axis and
pose serious threat to fish health and affect their population.
PMID- 24347049
TI - Direct amine-functionalisation of gamma-Fe2O3 nanoparticles.
AB - A novel and simple preparation of amine-modified gamma-Fe2O3 nanoparticles is
described. The presence of amine groups on the surface, instead of hydroxyl
groups, will allow conjugation of biologically active molecules to the iron oxide
nanoparticles without the need for a size increasing silica shell. Furthermore,
the outer amine-layer increases the temperature of the gamma-Fe2O3 to alpha-Fe2O3
structural transition in a similar way to previously reported cationic
substitutions. This may suggest the formation of an oxide-nitride outer layer. Re
dispersion of the amine-modified gamma-Fe2O3 nanoparticles led to the preparation
of stable ferrofluids.
PMID- 24347050
TI - Computationally simple estimation and improved efficiency for special cases of
double truncation.
AB - Doubly truncated survival data arise when event times are observed only if they
occur within subject specific intervals of times. Existing iterative estimation
procedures for doubly truncated data are computationally intensive (Turnbull
38:290-295, 1976; Efron and Petrosian 94:824-825, 1999; Shen 62:835-853, 2010a).
These procedures assume that the event time is independent of the truncation
times, in the sample space that conforms to their requisite ordering. This type
of independence is referred to as quasi-independence. In this paper we identify
and consider two special cases of quasi-independence: complete quasi-independence
and complete truncation dependence. For the case of complete quasi-independence,
we derive the nonparametric maximum likelihood estimator in closed-form. For the
case of complete truncation dependence, we derive a closed-form nonparametric
estimator that requires some external information, and a semi-parametric maximum
likelihood estimator that achieves improved efficiency relative to the standard
nonparametric maximum likelihood estimator, in the absence of external
information. We demonstrate the consistency and potentially improved efficiency
of the estimators in simulation studies, and illustrate their use in application
to studies of AIDS incubation and Parkinson's disease age of onset.
PMID- 24347051
TI - Spatial quantitation of FISH signals in diploid versus aneuploid nuclei.
AB - Fluorescence in situ hybridization (FISH) is the most widely used molecular
technique to visualize chromosomal abnormalities. Here, we describe a novel 3D
modeling approach to allow precise shape estimation and localization of FISH
signals in the nucleus of human embryonic stem cells (hES) undergoing progressive
but defined aneuploidy. The hES cell line WA09 acquires an extra copy of
chromosome 12 in culture with increasing passages. Both diploid and aneuploid
nuclei were analyzed to quantitate the differences in the localization of
centromeric FISH signals for chromosome 12 as it transitions from euploidy to
aneuploidy. We employed superquadric modeling primitives coupled with principal
component analysis to determine the 3D position of FISH signals within the
nucleus. A novel aspect of our modeling approach is that it allows comparison of
FISH signals across multiple cells by normalizing the position of the centromeric
signals relative to a reference landmark in oriented nuclei. Using this model we
present evidence of changes in the relative positioning of centromeres in trisomy
12 cells when compared with diploid cells from the same population. Our analysis
also suggests a significant change in the spatial distribution of at least one of
the FISH signals in the aneuploid chromosome complements implicating that an
overall change in centromere position may occur in trisomy-12 due to the addition
of an extra chromosome. These studies underscore the unique utility of our
modeling algorithms in quantifying FISH signals in three dimensions.
PMID- 24347052
TI - Core-sheath carbon nanostructured fibers for efficient wire-shaped dye-sensitized
solar cells.
AB - A novel core-sheath carbon nanostructured fiber is created with high tensile
strength, electrical conductivity, and electrocatalytic activity. In particular,
the designed ribbon-like nanostructure on the outer surface favors the attachment
and impregnation of a second functional phase that is critical for electronic
devices. As a demonstration, novel wire-shaped dye-sensitized solar cells are
produced with high energy conversion efficiencies up to 6.83%.
PMID- 24347053
TI - New cancer cachexia rat model generated by implantation of a peritoneal
dissemination-derived human stomach cancer cell line.
AB - Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss
due to low fat-free mass levels, including reduced musculature, markedly worsens
patient quality of life. Although stomach cancer patients have the highest
incidence of cachexia, few experimental models for the study of stomach CC have
been established. Herein, we developed stomach CC animal models using nude rats
subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established
from the human stomach cancer cell line MKN-45, and 85As2, derived from
peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice.
Both CC models showed marked weight loss, anorexia, reduced musculature and
muscle strength, increased inflammatory markers, and low plasma albumin levels;
however, CC developed earlier and was more severe in rats implanted with 85As2
than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory
factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA
levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA
levels decreased. Surgical removal of the tumor not only abolished cachexia
symptoms but also reduced plasma LIF levels to below detectable limits.
Importantly, oral administration of rikkunshito, a traditional Japanese medicine,
substantially ameliorated CC-related anorexia and body composition changes. In
summary, our novel peritoneal dissemination-derived 85As2 rat model developed
severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated
by rikkunshito. This model should provide a useful tool for further study into
the mechanisms and treatment of stomach CC.
PMID- 24347055
TI - Placental mitochondrial content and function in intrauterine growth restriction
and preeclampsia.
AB - Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such
as preeclampsia (PE) associated with IUGR share a common placental phenotype
called "placental insufficiency", originating in early gestation when high
availability of energy is required. Here, we assess mitochondrial content and the
expression and activity of respiratory chain complexes (RCC) in placental cells
of these pathologies. We measured mitochondrial (mt)DNA and nuclear respiratory
factor 1 (NRF1) expression in placental tissue and cytotrophoblast cells, gene
and protein expressions of RCC (real-time PCR and Western blotting) and their
oxygen consumption, using the innovative technique of high-resolution
respirometry. We analyzed eight IUGR, six PE, and eight uncomplicated human
pregnancies delivered by elective cesarean section. We found lower mRNA levels of
complex II, III, and IV in IUGR cytotrophoblast cells but no differences at the
protein level, suggesting a posttranscriptional compensatory regulation. mtDNA
was increased in IUGR placentas. Both mtDNA and NRF1 expression were instead
significantly lower in their isolated cytotrophoblast cells. Finally,
cytotrophoblast RCC activity was significantly increased in placentas of IUGR
fetuses. No significant differences were found in PE placentas. This study
provides genuine new data into the complex physiology of placental oxygenation in
IUGR fetuses. The higher mitochondrial content in IUGR placental tissue is
reversed in cytotrophoblast cells, which instead present higher mitochondrial
functionality. This suggests different mitochondrial content and activity
depending on the placental cell lineage. Increased placental oxygen consumption
might represent a limiting step in fetal growth restriction, preventing adequate
oxygen delivery to the fetus.
PMID- 24347054
TI - Dipeptidyl peptidase IV inhibitor lowers PPARgamma agonist-induced body weight
gain by affecting food intake, fat mass, and beige/brown fat but not fluid
retention.
AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists like
pioglitazone (PGZ) are effective antidiabetic drugs, but they induce fluid
retention and body weight (BW) gain. Dipeptidyl peptidase IV (DPP IV) inhibitors
are antidiabetic drugs that enhance renal Na(+) and fluid excretion. Therefore,
we examined whether the DPP IV inhibitor alogliptin (ALG) ameliorates PGZ-induced
BW gain. Male Sv129 mice were treated with vehicle (repelleted diet), PGZ (220
mg/kg diet), ALG (300 mg/kg diet), or a combination of PGZ and ALG (PGZ + ALG)
for 14 days. PGZ + ALG prevented the increase in BW observed with PGZ but did not
attenuate the increase in body fluid content determined by bioimpedance
spectroscopy (BIS). BIS revealed that ALG alone had no effect on fat mass (FM)
but enhanced the FM-lowering effect of PGZ; MRI analysis confirmed the latter and
showed reductions in visceral and inguinal subcutaneous (sc) white adipose tissue
(WAT). ALG but not PGZ decreased food intake and plasma free fatty acid
concentrations. Conversely, PGZ but not ALG increased mRNA expression of
thermogenesis mediator uncoupling protein 1 in epididymal WAT. Adding ALG to PGZ
treatment increased the abundance of multilocular cell islets in sc WAT, and PGZ
+ ALG increased the expression of brown-fat-like "beige" cell marker TMEM26 in sc
WAT and interscapular brown adipose tissue and increased rectal temperature vs.
vehicle. In summary, DPP IV inhibition did not attenuate PPARgamma agonist
induced fluid retention but prevented BW gain by reducing FM. This involved ALG
inhibition of food intake and was associated with food intake-independent
synergistic effects of PPARgamma agonism and DPP-IV inhibition on beige/brown fat
cells and thermogenesis.
PMID- 24347056
TI - Validation of surrogate indexes of insulin sensitivity in acute phase of
myocardial infarction based on euglycemic-hyperinsulinemic clamp.
AB - The decrease in insulin sensitivity (IS) during myocardial infarction (MI) is
recognized as a possible contributor to poor patient outcomes. Despite its
potential relevance, a standardized and convenient IS assessment tool has yet to
be established for said clinical scenarios. This study aimed to validate the
accuracy of surrogate indexes in determining IS in acute MI patients by
comparison with the gold standard reference method for measuring IS, the
euglycemic-hyperinsulinemic clamp (EHC). We performed EHCs in 31 consecutive
nondiabetic patients who were admitted within the first 24 h of symptoms of ST
segment elevation MI. Patients with prior diagnosis of diabetes, use of
hypoglycemic agents, or a glycosylated hemoglobin >=6.5% were excluded. EHCs were
performed at the second day (D2) and sixth day (D6) post-MI. Basal (12-h fasting)
blood samples from D2 and D6 were used to evaluate patient blood glucose and
insulin levels. We then calculated the following surrogate indexes: homeostatic
model assessment of insulin sensitivity (HOMA2S), homeostatic model assessment of
insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index
(QUICKI). The IS index measured by EHC (ISiclamp) was correlated to HOMA2S, HOMA
IR, and QUICKI at D2 (r = 0.485, P = 0.009; r = -0.384, P = 0.048; r = 0.479, P =
0.01, respectively) and D6 (r = 0.621, P = 0.002; r = -0.576, P = 0.006; r =
0.626, P = 0.002, respectively). Receiver operator characteristic curves made for
discrimination of ISiclamp above the median in D2 and D6 depicted areas under the
curve of 0.740, 0.734, and 0.760 for HOMA2S, HOMA-IR, and QUICKI, respectively.
Bland-Altman plots displayed no apparent systematic error for indexes, but a
propensity for proportional error, particularly with HOMA-IR. Thus, based on EHC,
these simple surrogate indexes are feasible for assessing IS during MI.
PMID- 24347057
TI - Blockade of the cerebral aqueduct in rats provides evidence of antagonistic
leptin responses in the forebrain and hindbrain.
AB - Previously, we reported that low-dose leptin infusions into the fourth ventricle
produced a small but significant increase in body fat. These data contrast with
reports that injections of higher doses of leptin into the fourth ventricle
inhibit food intake and weight gain. In this study, we tested whether exogenous
leptin in the fourth ventricle opposed or contributed to weight loss caused by
third ventricle leptin infusion by blocking diffusion of CSF from the third to
the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions
of PBS or 0.3 MUg leptin/24 h from miniosmotic pumps. After 4 days, rats received
a 3-MUl cerebral aqueduct injection of saline or of thermogelling nanoparticles
(hydrogel) that solidified at body temperature. Third ventricle leptin infusion
inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated
the effect of leptin on food intake and weight loss but had no effect on the
weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but
did not change energy expenditure. Blocking the aqueduct decreased expenditure of
rats infused with PBS or leptin. Infusion of leptin into the third ventricle
increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial
NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3
but decreased p-STAT3 in the medial NTS. These results support previous
observations that low-level activation of hindbrain leptin receptors has the
potential to blunt the catabolic effects of leptin in the third ventricle.
PMID- 24347058
TI - Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the
induction of FGF21 as a myokine.
AB - UCP1-Tg mice with ectopic expression of uncoupling protein 1 (UCP1) in skeletal
muscle (SM) are a model of improved substrate metabolism and increased longevity.
Analysis of myokine expression showed an induction of fibroblast growth factor 21
(FGF21) in SM, resulting in approximately fivefold elevated circulating FGF21 in
UCP1-Tg mice. Despite a reduced muscle mass, UCP1-Tg mice showed no evidence for
a myopathy or muscle autophagy deficiency but an activation of integrated stress
response (ISR; eIF2alpha/ATF4) in SM. Targeting mitochondrial function in vitro
by treating C2C12 myoblasts with the uncoupler FCCP resulted in a dose-dependent
activation of ISR, which was associated with increased expression of FGF21, which
was also observed by treatment with respiratory chain inhibitors antimycin A and
myxothiazol. The cofactor required for FGF21 action, beta-klotho, was expressed
in white adipose tissue (WAT) of UCP1-Tg mice, which showed an increased browning
of WAT similar to what occurred in altered adipocyte morphology, increased brown
adipocyte markers (UCP1, CIDEA), lipolysis (HSL phosphorylation), and respiratory
capacity. Importantly, treatment of primary white adipocytes with serum of
transgenic mice resulted in increased UCP1 expression. Additionally, UCP1-Tg mice
showed reduced body length through the suppressed IGF-I-GH axis and decreased
bone mass. We conclude that the induction of FGF21 as a myokine is coupled to
disturbance of mitochondrial function and ISR activation in SM. FGF21 released
from SM has endocrine effects leading to increased browning of WAT and can
explain the healthy metabolic phenotype of UCP1-Tg mice. These results confirm
muscle as an important endocrine regulator of whole body metabolism.
PMID- 24347059
TI - AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through
the HSP72-mediated pathway in C2C12 skeletal muscle cells.
AB - 5'-AMP-activated protein kinase (AMPK) plays an important role as a negative
regulator of skeletal muscle mass. However, the precise mechanism of AMPK
mediated regulation of muscle mass is not fully clarified. Heat shock proteins
(HSPs), stress-induced molecular chaperones, are related with skeletal muscle
adaptation, but the association between AMPK and HSPs in skeletal muscle
hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy
by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator
of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes
in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock
transcription factor 1 in myotubes. Protein content and diameter were less in the
AICAR-treated myotubes in those without treatment. AICAR-induced suppression of
myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated
AMPKalpha knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of
HSP72, and the increase of miR-1 was not induced in AMPKalpha knockdown
condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICAR-induced
inhibition of myotube hypertrophy. AICAR upregulated the gene expression of
muscle Ring-finger 1, and this alteration was suppressed in either AMPKalpha or
HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr(389) was
downregulated by AICAR, whereas this was attenuated in AMPKalpha, but not in
HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy
through, in part, an HSP72-associated mechanism via miR-1 and protein degradation
pathways in skeletal muscle cells.
PMID- 24347060
TI - Role of bone morphogenetic protein 4 in the differentiation of brown fat-like
adipocytes.
AB - There are two different types of fat present in mammals: white adipose tissue,
the primary site of energy storage, and brown adipose tissue, which is
specializes in energy expenditure. Factors that specify the developmental fate
and function of brown fat are poorly understood. Bone morphogenic proteins (BMPs)
play an important role in adipogenesis. While BMP4 is capable of triggering
commitment of stem cells to the white adipocyte lineage, BMP7 triggers commitment
of progenitor cells to a brown adipocyte lineage and activates brown
adipogenesis. To investigate the differential effects of BMPs on the development
of adipocytes, C3H10T1/2 pluripotent cells were pretreated with BMP4 and BMP7,
followed by different adipogenic induction cocktails. Both BMP4 and BMP7
unexpectedly activated a full program of brown adipogenesis, including induction
of the brown fat-defining marker uncoupling protein-1 (UCP1), increasing the
expression of early regulators of brown fat fate PRDM16 (PR domain-containing 16)
and induction of mitochondrial biogenesis and function. Implantation of BMP4
pretreated C3H10T1/2 cells into nude mice resulted in the development of adipose
tissue depots containing UCP1-positive brown adipocytes. Interestingly, BMP4
could also induce brown fat-like adipocytes in both white and brown
preadipocytes, thereby decreasing the classical brown adipocyte marker Zic1 and
increasing the recently identified beige adipocyte marker TMEM26. The data
indicate an important role for BMP4 in promoting brown adipocyte differentiation
and thermogenesis in vivo and in vitro and offers a potentially new therapeutic
approach for the treatment of obesity.
PMID- 24347061
TI - Tolerance of an aerobic denitrifier (Pseudomonas stutzeri) to high O2
concentrations.
AB - An aerobic denitrifier was isolated from activated sludge and the isolate
possessed an average removal rate of 5.7 mg NO3 (-)-N l(-1) h(-1) without
accumulation of NO2 (-)-N (less than 2.1 mg l(-1)). The average removal
efficiency of nitrate was 93.7 % in 24 h, when the dissolved oxygen (DO)
concentrations ranged from 3.2 to 17.5 mg l(-1). The activity of both nap
(periplasmic nitrate reductase) and nir (nitrite reductase), whose corresponding
genes (napA and nirS) were amplified by touchdown PCR, could be responsible for
the tolerance of DO concentrations. Other three genes relating to narG, norB and
nosZ were noted to involve in isolate strain.
PMID- 24347063
TI - A good year.
PMID- 24347062
TI - Pediatric temporal bone fractures: current trends and comparison of
classification schemes.
AB - OBJECTIVES: 1) Characterize the current presentation of pediatric temporal bone
fractures, 2) compare two classification schemes for temporal bone fractures and
illustrate complications in each fracture type. DESIGN: Retrospective medical
record review. SETTING: Tertiary-care, academic children's hospital. PATIENTS:
All children presenting from 1999 to 2009 with CT-proven temporal bone fracture
and audiology examination with follow-up. INTERVENTION: All CT scans were
reinterpreted by a dedicated head and neck radiologist. All fractures were
characterized as otic capsule sparing (OCS) or otic capsule violating (OCV), as
well as transverse (T) or longitudinal (L). OUTCOME: CT findings, mechanisms of
injury, sensorineural hearing loss (SNHL), conductive hearing loss (CHL), and
facial nerve injury (FNI). RESULTS: Seventy-one children met inclusion criteria.
Fifty-four (76%) children had longitudinal fractures versus 17 (24%) with
transverse fractures. Sixty-four (90%) had OCS versus 7 (10%) with OCV. The otic
capsule was involved in 7.4% of longitudinal fractures and 17.6% of transverse
fractures. Eleven (15%) had facial weakness, 72% of whom had a visualized
fracture through the facial nerve course. SNHL was detected in 14 (20%) patients
and CHL in 17(23.9%). All patients with fractures classified as both transverse
and OCV had SNHL. The OCS versus OCV and T versus L classification schemes were
directly compared for statistical significance in predicting SNHL, CHL, and FNI
using the Fisher's exact test. Both OCS/OCV and T/L were predictors of SNHL (P =
.0025 and P = .0143, respectively), but the OCS/OCV scheme was more accurate.
Neither classification significantly predicted CHL or FNI (P = .787 versus .825;
P = .705 vs. .755). CONCLUSIONS: In this pediatric series, approximately 75% of
the fractures are longitudinal and 25% are transverse. The otic capsule is spared
in 90% and violated in 10%. Both OCS/OCV and L/T classification schemes predict
SNHL, but the OCV/OCS scheme is more accurate in this prediction. Although the
negative predictive value of the two schemes is similar, the positive predictive
value is higher with the OCS/OCV system. The presence of conductive hearing loss
and facial nerve symptoms was not predicted by either classification system.
PMID- 24347066
TI - The combination of chemotherapy and radiotherapy towards more efficient drug
delivery.
AB - Research on anticancer therapies has advanced significantly in recent years. New
therapeutic platforms that can further improve the health of patients are still
highly demanded. We propose the idea of combining regular chemotherapy with
radiation therapy to minimize side effects as well as increase drug-delivery
efficiency. In this Focus Review, we seek to provide an overview of recent
advances that can combine chemotherapy and radiotherapy. We begin by reviewing
the current state of systems that can combine chemotherapy and gamma radiation.
Among them, diselenide-containing polymers are highlighted as sensitive drug
delivery vehicles that can disassemble under gamma radiation. Then X-ray
responsive materials as promising alternative systems are summarized, including X
ray responsive drug-delivery vehicles, prodrugs that can be activated by X-rays,
and radiation-site-targeting systems. Finally, we describe strategies that
involve phototherapies.
PMID- 24347067
TI - Chemoenzymatic routes to polyoxygenated cyclooctenones related to the Eastern
hemisphere of the macrolactam tripartilactam.
AB - Polyoxygenated cyclooctenones closely related to the enantiomeric form of the
Eastern hemisphere of the structurally and biogenetically unusual macrolactam
tripartilactam have been assembled from an enzymatically-derived and homochiral
cis-1,2-dihydrocatechol. Key steps include the oxidative cleavage of the
chlorinated double bond within a derivative of the starting cis-1,2
dihydrocatechol and a ring-closing metathesis reaction to establish the required
eight-membered ring.
PMID- 24347068
TI - Chemoselective hydrogenation of functionalized nitroarenes and imines by using
carbon nanofiber-supported iridium nanoparticles.
AB - The reaction of three types of carbon nanofibers (CNFs; platelet: CNF-P, tubular:
CNF-T, herringbone: CNF-H) with Ir4(CO)12 in mesitylene at 165 degrees C
provided the corresponding CNF-supported iridium nanoparticles, Ir/CNFs (Ir
content=2.3-2.6 wt.%). Transmission electron microscopy (TEM) studies of these
Ir/CNF samples revealed that size-controlled Ir nanoparticles (average particle
size of 1.1-1.5 nm) existed on the CNFs. Among the three Ir/CNF samples, Ir/CNF-T
showed an excellent catalytic activity and chemoselectivity towards hydrogenation
of functionalized nitroarenes and imines; the corresponding aniline derivatives
were obtained with high turnover numbers at ambient temperature under 10 tm of H2
, and the catalyst is reusable. Ir/CNF-T was also effective for the reductive N
alkylation of anilines with carbonyl compounds.
PMID- 24347069
TI - Photocontrolled intramolecular charge/energy transfer and fluorescence switching
of tetraphenylethene-dithienylethene-perylenemonoimide triad with donor-bridge
acceptor structure.
AB - Photochromic 1,2-dithienylethene (DTE) derivatives with a high thermal stability
and fatigue resistance are appealing for optical switching of fluorescence. Here,
we introduce a donor-photochromic bridge-acceptor tetraphenylethene
dithienylethene-perylenemonoimide (TPE-DTE-PMI) triad, in which TPE acts as the
electron donor, PMI as the electron acceptor, and DTE as the photochromic bridge.
In this system, the localized and intramolecular charge transfer emission of TPE
DTE-PMI with various Stokes shifts have been observed due to the photoinduced
intramolecular charge transfer in different solvents. Upon UV irradiation, the
fluorescence quenching resulting from photochromic fluorescence resonance energy
transfer in TPE-DTE-PMI has been demonstrated in solution and in solid films. The
fluorescence on/off switching ratio in polymethylacrylate film exceeds 100, a
value much higher than in polymethylmethacrylate film, thus indicating that the
fluorescence switching is dependent on matrices.
PMID- 24347070
TI - Hydrophobic variations of N-oxide amphiphiles for membrane protein manipulation:
importance of non-hydrocarbon groups in the hydrophobic portion.
AB - Amphipathic agents called detergents serve as membrane-mimetic systems to
maintain the native structures of membrane proteins during their manipulation.
However, membrane proteins solubilized in conventional detergents tend to undergo
denaturation and aggregation, necessitating the development of novel amphipathic
agents with enhanced properties. Here we describe several new amphiphiles that
contain an N-oxide group as the hydrophilic portion. The new amphiphiles have
been evaluated for the ability to solubilize and stabilize a fragile multi
subunit assembly from biological membranes. We found that cholate-based agents
were promising in supporting retention of the native protein quaternary
structure, while deoxycholate-based amphiphiles were highly efficient in
extracting/solubilizing the intact superassembly from the native membrane.
Monitoring superassembly solubilization and stabilization as a function of
variation in amphiphile structure led us to propose that a non-hydrocarbon moiety
such as an amide, ether, or a hydroxy group present in the lipophilic regions can
manifest distinctive effects in the context of membrane protein manipulation.
PMID- 24347071
TI - Pyridinium-fused pyridinone: a novel "turn-on" fluorescent chemodosimeter for
cyanide.
AB - A new chemodosimeter based on pyridinium-fused pyridinone iodide (PI) has been
obtained through a "clean reaction" method. This compound can detect CN(-) in
aqueous solution with a high selectivity and rapid response. The detection of CN(
) occurs through the nucleophilic attack of CN(-) on the C=N bond, which induces
the destruction of the pi-conjugation on the pyridinium ring. Support of this
detection mechanism was obtained by (1)H NMR titration, HR-MS, and DFT
calculations. Upon the addition of 10 equivalents CN(-) to a solution of PI in
THF/H2 O (1:1, v/v), a 57-fold enhancement in fluorescence intensity was observed
at the maximum emission wavelength of 457 nm. Meanwhile, the maximum absorption
wavelength was also blue-shifted from 447 nm to 355 nm. Other common anions such
as BF4(-), PF6(-), F(-), Cl(-), Br(-), I(-), H2PO4(-), ClO4(-), CH3 COO(-) , NO2
(-) , N3 (-) , and SCN(-) had little effect on the detection of CN(-). The
response time of PI for CN(-) was less than 5 seconds. The detection limit was
calculated to be 5.4*10(-8) M, which is lower than the maximum permission
concentration in drinking water (1.9 MUM) set by the World Health Organization
(WHO).
PMID- 24347072
TI - Highly selective "turn-on" fluorescent and colorimetric sensing of fluoride ion
using 2-(2-hydroxyphenyl)-2,3-dihydroquinolin-4(1H)-one based on excited-state
proton transfer.
AB - A simple, highly selective and sensitive colorimetric system for the detection of
fluoride ion in an aqueous medium has been developed using 2-(2-hydroxyphenyl)
2,3-dihydroquinolin-4(1H)-one. This system allows selective "turn-on"
fluorescence detection of fluoride ion, which is found to be dependent upon guest
basicity. An excited-state proton transfer is proposed to be the signaling
mechanism, which is rationalized by DFT and TD-DFT calculations. The present
sensor can also be applied to detect fluoride levels in real water samples.
PMID- 24347073
TI - Copper-catalyzed C-H bond direct chalcogenation of aromatic compounds leading to
diaryl sulfides, selenides, and diselenides by using elemental sulfur and
selenium as chalcogen sources under oxidative conditions.
AB - The reactions of aromatic compounds and elemental chalcogens catalyzed by a
copper salt with molecular oxygen as an oxidant were carried out. The reaction of
3-substituted imidazo[1,5-a]pyridines and elemental sulfur in the presence of
CuTC (copper(I) thiophenecarboxylate) gave the corresponding bisimidazopyridyl
sulfides in good to quantitative yields. The reaction proceeded even under
aerobic oxidation conditions. The use of a polar solvent was crucial for the
reaction, and DMSO (dimethyl sulfoxide) in particular stimulated the reaction.
The reaction could be applied to common aromatic compounds, such as N-methyl
indole and dialkyl anilines. The reaction of indole proceeded at the nucleophilic
C3 position rather than at the acidic C2 position. In addition, the reaction of
dialkyl anilines proceeded with an ortho, para orientation. The reactions of
imidazopyridines and elemental selenium under similar conditions gave the
corresponding bisimidazopyridyl diselenides along with bisimidazopyridyl
monoselenides. The resulting diselenides were readily converted to the
corresponding monoselenides with unreacted imidazopyridines under the same
conditions. The reaction could be applied to the copolymerization of bifunctional
bisimidazopyridines and elemental sulfur to give oligomeric copolymers in
quantitative yield.
PMID- 24347075
TI - Compositing amorphous TiO2 with N-doped carbon as high-rate anode materials for
lithium-ion batteries.
AB - Compositing amorphous TiO2 with nitrogen-doped carbon through Ti-N bonding to
form an amorphous TiO2/N-doped carbon hybrid (denoted a-TiO2/C-N) has been
achieved by a two-step hydrothermal-calcining method with hydrazine hydrate as an
inhibitor and nitrogen source. The resultant a-TiO2/C-N hybrid has a surface area
as high as 108 m(2) g(-1) and, when used as an anode material, exhibits a
capacity as high as 290.0 mA h g(-1) at a current rate of 1 C and a reversible
capacity over 156 mA h g(-1) at a current rate of 10 C after 100 cycles; these
results are better than those found in most reports on crystalline TiO2 . This
superior electrochemical performance could be ascribed to a combined effect of
several factors, including the amorphous nature, porous structure, high surface
area, and N-doped carbon.
PMID- 24347074
TI - Gold nanorods with phase-changing polymer corona for remotely near-infrared
triggered drug release.
AB - Herein, we report a new drug-delivery system (DDS) that is comprised of a near
infrared (NIR)-light-sensitive gold-nanorod (GNR) core and a phase-changing
poly(epsilon-caprolactone)-b-poly(ethylene glycol) polymer corona (GNR@PCL-b
PEG). The underlying mechanism of the drug-loading and triggered-release
behaviors involves the entrapment of drug payloads among the PCL crystallites and
a heat-induced phase change, respectively. A low premature release of the pre
loaded doxorubicin was observed in PBS buffer (pH 7.4) at 37 degrees C (<10% of
the entire payload after 48 h). However, release could be activated within 30 min
by conventional heating at 50 degrees C, above the Tm of the crystalline PCL
domain (43.5 degrees C), with about 60% release over the subsequent 42 h at 37
degrees C. The NIR-induced heating of an aqueous suspension of GNR@PCL-b-PEG
under NIR irradiation (802 nm) was investigated in terms of the irradiation
period, power, and concentration-dependent heating behavior, as well as the NIR
induced shape-transformation of the GNR cores. Remotely NIR-triggered release was
also explored upon NIR irradiation for 30 min and about 70% release was achieved
in the following 42 h at 37 degrees C, with a mild warming (<4 degrees C) of
the surroundings. The cytotoxicity of GNR@PCL-b-PEG against the mouse
fibroblastic-like L929 cell-line was assessed by MTS assay and good compatibility
was confirmed with a cell viability of over 90% after incubation for 72 h. The
cellular uptake of GNR@PCL-b-PEG by melanoma MEL-5 cells was also confirmed, with
an averaged uptake of 1250(+/-110) particles cell(-1) after incubation for 12 h
(50 MUg mL(-1)). This GNR@PCL-b-PEG DDS is aimed at addressing the different
requirements for therapeutic treatments and is envisaged to provide new insights
into DDS targeting for remotely triggered release by NIR activation.
PMID- 24347076
TI - High-performance dye-sensitized solar cells based on phenothiazine dyes
containing double anchors and thiophene spacers.
AB - A series of new push-pull phenothiazine-based dyes (HL1-HL4) featuring various pi
spacers (thiophene, 3-hexylthiophene, 4-hexyl-2,2'-bithiophene) and double
acceptors/anchors have been synthesized, characterized, and used as sensitizers
for dye-sensitized solar cells (DSSCs). Among them, the best conversion
efficiency (7.31%) reaches approximately 99% of the N719-based (7.38%) DSSCs
fabricated and measured under similar conditions. The dyes with two anchors have
more efficient interfacial charge generation and transport compared with their
congeners with only single anchor. Incorporation of hexyl chains into the pi
conjugated spacer of these double-anchoring dyes can efficiently suppress dye
aggregation and reduce charge recombination.
PMID- 24347077
TI - Inhaled corticosteroids and bone mineral density at school age: a follow-up study
after early childhood wheezing.
AB - OBJECTIVE: The aim of the study was to evaluate the association between previous
use of ICS and bone mineral density (BMD) at school age in a cohort followed
after early childhood wheezing. METHODS: As part of a prospective follow-up study
after hospitalization for wheezing at <24 months of age, BMD was measured in 89
children at 12.3 (median) years of age. Data on ICS use were collected by
interviewing the parents, and this was supplemented with data from patient
records. Cumulative doses and the duration of ICS use were calculated. Areal BMD
(BMDareal , g/cm(2) ) was measured by dual energy X-ray absorptiometry (DXA), and
apparent volumetric BMD (aBMDvol , g/cm(3) ) was calculated, for the lumbar spine
and femoral neck. Weight, height and pubertal stage were recorded. FINDINGS: Age,
sex, and pubertal stage were significantly associated with BMDareal and aBMDvol
of the lumbar spine and BMDareal of the femoral neck. The regular use of ICS for
>6 months at age <6 years was associated with a lower BMD of the lumbar spine. A
lower BMDareal and aBMDvol of the femoral neck were associated with higher
cumulative doses of ICS at age 0-12.3 (median) years. The results were robust to
adjustment for age, sex, pubertal stage, height, weight, and use of systemic
steroids. CONCLUSION: ICS use during childhood may be related to a decrease in
BMD at late school age. It is important to use the lowest possible ICS dose that
maintains adequate asthma control.
PMID- 24347085
TI - Variation in phenolic compounds, anthocyanins, and color in red wine treated with
enzymatic extract of Kluyveromyces marxianus.
AB - The effect of the addition of enzymatic extract of Kluyveromyces marxianus NRRL-Y
7571 during the maceration and fermentation steps of Cabernet Sauvignon wine
production was evaluated. The results obtained in the analytical determinations
of the wines showed levels within the limits established by legislation and
similar to values found in other studies. The results show that by adding the
enzyme to the red wines these showed color characteristics considered to be
superior to those of the control wine and accelerated the extraction of phenolic
compounds and anthocyanins. It was observed that by using the commercial enzyme
preparation there was an increase of 15 % in polyphenol content compared to the
control wine and an increase of 28 % when the crude enzyme extract was used.
Anthocyanin content in the wine increased after treatment with the commercial
enzyme preparation (10 %) and with the use of the crude enzymatic extract (22 %).
Considering all comparison criteria, the K. marxianus enzymatic extract showed
results statistically similar or superior to those obtained with the commercial
enzyme preparation.
PMID- 24347086
TI - Detecting and correcting partial errors: Evidence for efficient control without
conscious access.
AB - Appropriate reactions to erroneous actions are essential to keeping behavior
adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG)
recordings of the responding muscles have revealed that covert incorrect response
activations (termed "partial errors") occur on a proportion of overtly correct
trials. The occurrence of such "partial errors" shows that incorrect response
activations could be corrected online, before turning into overt errors. In the
present study, we showed that, unlike overt errors, such "partial errors" are
poorly consciously detected by participants, who could report only one third of
their partial errors. Two parameters of the partial errors were found to predict
detection: the surface of the incorrect EMG burst (larger for detected) and the
correction time (between the incorrect and correct EMG onsets; longer for
detected). These two parameters provided independent information. The
correct(ive) responses associated with detected partial errors were larger than
the "pure-correct" ones, and this increase was likely a consequence, rather than
a cause, of the detection. The respective impacts of the two parameters
predicting detection (incorrect surface and correction time), along with the
underlying physiological processes subtending partial-error detection, are
discussed.
PMID- 24347087
TI - Management of faecal incontinence and constipation in adults with central
neurological diseases.
AB - BACKGROUND: People with central neurological disease or injury have a much higher
risk of both faecal incontinence and constipation than the general population.
There is often a fine line between the two symptoms, with any management intended
to ameliorate one risking precipitating the other. Bowel problems are observed to
be the cause of much anxiety and may reduce quality of life in these people.
Current bowel management is largely empirical, with a limited research base. This
is an update of a Cochrane review first published in 2001 and subsequently
updated in 2003 and 2006. The review is relevant to individuals with any disease
directly and chronically affecting the central nervous system (post-traumatic,
degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord
injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease.
OBJECTIVES: To determine the effects of management strategies for faecal
incontinence and constipation in people with a neurological disease or injury
affecting the central nervous system. SEARCH METHODS: We searched the Cochrane
Incontinence Group Trials Register (searched 8 June 2012), which includes
searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
and MEDLINE In-Process as well as handsearching of journals and conference
proceedings; and all reference lists of relevant articles. SELECTION CRITERIA:
Randomised and quasi-randomised trials evaluating any type of conservative or
surgical intervention for the management of faecal incontinence and constipation
in people with central neurological disease or injury were selected. Specific
therapies for the treatment of neurological diseases that indirectly affect bowel
dysfunction were also considered. DATA COLLECTION AND ANALYSIS: Two review
authors independently assessed the risk of bias of eligible trials and
independently extracted data from the included trials using a range of pre
specified outcome measures. MAIN RESULTS: Twenty trials involving 902 people were
included.Oral medicationsThere was evidence from individual small trials that
people with Parkinson's disease had a statistically significant improvement in
the number of bowel motions or successful bowel care routines per week when fibre
(psyllium) (mean difference (MD) -2.2 bowel motions, 95% confidence interval (CI)
-3.3 to -1.4) or oral laxative (isosmotic macrogol electrolyte solution) (MD 2.9
bowel motions per week, 95% CI 1.48 to 4.32) are used compared with placebo. One
trial in people with spinal cord injury showed statistically significant
improvement in total bowel care time comparing intramuscular neostigmine
glycopyrrolate (anticholinesterase plus an anticholinergic drug) with placebo (MD
23.3 minutes, 95% CI 4.68 to 41.92).Five studies reported the use of cisapride
and tegaserod in people with spinal cord injuries or Parkinson's disease. These
drugs have since been withdrawn from the market due to adverse effects; as they
are no longer available they have been removed from this review.Rectal
stimulantsOne small trial in people with spinal cord injuries compared two
bisacodyl suppositories, one polyethylene glycol-based (PGB) and one hydrogenated
vegetable oil-based (HVB). The trial found that the PGB bisacodyl suppository
significantly reduced the mean defaecation period (PGB 20 minutes versus HVB 36
minutes, P < 0.03) and mean total time for bowel care (PGB 43 minutes versus HVB
74.5 minutes, P < 0.01) compared with the HVB bisacodyl suppository.Physical
interventionsThere was evidence from one small trial with 31 participants that
abdominal massage statistically improved the number of bowel motions in people
who had a stroke compared with no massage (MD 1.7 bowel motions per week, 95% CI
2.22 to 1.18). A small feasibility trial including 30 individuals with multiple
sclerosis also found evidence to support the use of abdominal massage.
Constipation scores were statistically better with the abdominal massage during
treatment although this was not supported by a change in outcome measures (for
example the neurogenic bowel dysfunction score).One small trial in people with
spinal cord injury showed statistically significant improvement in total bowel
care time using electrical stimulation of abdominal muscles compared with no
electrical stimulation (MD 29.3 minutes, 95% CI 7.35 to 51.25).There was evidence
from one trial with a low risk of bias that for people with spinal cord injury
transanal irrigation, compared against conservative bowel care, statistically
improved constipation scores, neurogenic bowel dysfunction score, faecal
incontinence score and total time for bowel care (MD 27.4 minutes, 95% CI 7.96 to
46.84). Patients were also more satisfied with this method.Other interventionsIn
one trial in stroke patients, there appeared to be a short term benefit (less
than six months) to patients in terms of the number of bowel motions per week
with a one-off educational intervention from nurses (a structured nurse
assessment leading to targeted education versus routine care), but this did not
persist at 12 months. A trial in individuals with spinal cord injury found that a
stepwise protocol did not reduce the need for oral laxatives and manual
evacuation of stool.Finally, one further trial reported in abstract form showed
that oral carbonated water (rather than tap water) improved constipation scores
in people who had had a stroke. AUTHORS' CONCLUSIONS: There is still remarkably
little research on this common and, to patients, very significant issue of bowel
management. The available evidence is almost uniformly of low methodological
quality. The clinical significance of some of the research findings presented
here is difficult to interpret, not least because each intervention has only been
addressed in individual trials, against control rather than compared against each
other, and the interventions are very different from each other.There was very
limited evidence from individual trials in favour of a bulk-forming laxative
(psyllium), an isosmotic macrogol laxative, abdominal massage, electrical
stimulation and an anticholinesterase-anticholinergic drug combination
(neostigmine-glycopyrrolate) compared to no treatment or controls. There was also
evidence in favour of transanal irrigation (compared to conservative management),
oral carbonated (rather than tap) water and abdominal massage with lifestyle
advice (compared to lifestyle advice alone). However, these findings need to be
confirmed by larger well-designed controlled trials which should include
evaluation of the acceptability of the intervention to patients and the effect on
their quality of life.
PMID- 24347088
TI - Breathing exercises for dysfunctional breathing/hyperventilation syndrome in
children.
AB - BACKGROUND: Dysfunctional breathing is described as chronic or recurrent changes
in breathing pattern causing respiratory and non-respiratory symptoms. It is an
umbrella term that encompasses hyperventilation syndrome and vocal cord
dysfunction. Dysfunctional breathing affects 10% of the general population.
Symptoms include dyspnoea, chest tightness, sighing and chest pain which arise
secondary to alterations in respiratory pattern and rate. Little is known about
dysfunctional breathing in children. Preliminary data suggest 5.3% or more of
children with asthma have dysfunctional breathing and that, unlike in adults, it
is associated with poorer asthma control. It is not known what proportion of the
general paediatric population is affected. Breathing training is recommended as a
first-line treatment for adults with dysfunctional breathing (with or without
asthma) but no similar recommendations are available for the management of
children. As such, breathing retraining is adapted from adult regimens based on
the age and ability of the child. OBJECTIVES: To determine whether breathing
retraining in children with dysfunctional breathing has beneficial effects as
measured by quality of life indices.To determine whether there are any adverse
effects of breathing retraining in young people with dysfunctional breathing.
SEARCH METHODS: We identified trials for consideration using both electronic and
manual search strategies. We searched CENTRAL, MEDLINE and EMBASE. We searched
the National Research Register (NRR) Archive, Health Services Research Projects
in Progress (HSRProj), Current Controlled Trials register (incorporating the
metaRegister of Controlled Trials and the International Standard Randomised
Controlled Trial Number (ISRCTN) to identify research in progress and unpublished
research. The latest search was undertaken in October 2013. SELECTION CRITERIA:
We planned to include randomised, quasi-randomised or cluster-randomised
controlled trials. We excluded observational studies, case studies and studies
utilising a cross-over design. The cross-over design was considered inappropriate
due to the purported long-lasting effects of breathing retraining. Children up to
the age of 18 years with a clinical diagnosis of dysfunctional breathing were
eligible for inclusion. We planned to include children with a primary diagnosis
of asthma with the intention of undertaking a subgroup analysis. Children with
symptoms secondary to cardiac or metabolic disease were excluded.We considered
any type of breathing retraining exercise for inclusion in this review, such as
breathing control, diaphragmatic breathing, yoga breathing, Buteyko breathing,
biofeedback-guided breathing modification and yawn/sigh suppression. We
considered programmes where exercises were either supervised (by parents or a
health professional, or both) or unsupervised. We also considered relaxation
techniques and acute episode management as long as it was clear that breathing
exercises were a component of the intervention.Any intervention without breathing
exercises or where breathing exercises were not key to the intervention were
excluded. DATA COLLECTION AND ANALYSIS: We planned that two authors (NJB and MJ)
would extract data independently using a standardised form. Any discrepancies
would be resolved by consensus. Where agreement could not be reached a third
review author (MLE) would have considered the paper. MAIN RESULTS: We identified
264 potential trials and reviews from the search. Following removal of
duplicates, we screened 224 papers based on title and abstract. We retrieved six
full-text papers and further evaluated them but they did not meet the inclusion
criteria. There were, therefore, no studies suitable for inclusion in this
review. AUTHORS' CONCLUSIONS: The results of this systematic review cannot inform
clinical practice as no suitable trials were identified for inclusion. Therefore,
it is currently unknown whether these interventions offer any added value in this
patient group or whether specific types of breathing exercise demonstrate
superiority over others. Given that breathing exercises are frequently used to
treat dysfunctional breathing/hyperventilation syndrome, there is an urgent need
for well-designed clinical trials in this area. Future trials should conform to
the CONSORT statement for standards of reporting and use validated outcome
measures. Trial reports should also ensure full disclosure of data for all
important clinical outcomes.
PMID- 24347089
TI - Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity
in rats.
AB - We investigated the therapeutic effectiveness of the nanoparticle-encapsulated
curcumin (CUR-NP) against sodium arsenite-induced hepatic oxidative damage in
rats. The CUR-NP prepared by emulsion technique was spherical in shape with an
encapsulation efficiency of 86.5%. The particle size ranged between 120 and 140
nm with the mean particle size being 130.8 nm. Rats were divided into five groups
of six each. Group 1 served as control. Group 2 rats were exposed to sodium
arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5
were treated with arsenic as in group 2, however, they were administered, empty
nanoparticles, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively,
by oral gavage during the last 14 days of arsenic exposure. Arsenic increased the
activities of serum alanine aminotransferase and aspartate aminotransferase and
caused histological alterations in liver indicating hepatotoxicity. Arsenic
increased lipid peroxidation, depleted reduced glutathione and decreased the
activities of superoxide dismutase, catalase, glutathione peroxidase and
glutathione reductase in liver. All these effects of arsenic were attenuated with
both curcumin and CUR-NP. However, the magnitude of amelioration was more
pronounced with CUR-NP. The results indicate that curcumin given in nano
encapsulated form caused better amelioration than free curcumin. (c) 2013 Wiley
Periodicals, Inc. Environ Toxicol 30: 628-637, 2015.
PMID- 24347090
TI - Understanding the continuum of maternal morbidity in Accra, Ghana.
AB - The objective was to determine the levels of maternal morbidity from no
complications to near miss and describe factors associated with different levels
of morbidity. We conducted an observational study of all women delivering at a
tertiary hospital in Accra, Ghana between October 2010 and March 2011. We
examined the factors associated with the continuum of maternal outcomes in terms
of severity using multinomial logistic regression. Data were extracted from
women's maternal care files with the main outcome measures of no complications,
non-life threatening complications, potentially life-threatening conditions
(PLTC), and near miss as defined by World Health Organization. Our study includes
1,586 women with no complications, 1,205 women with non-life threatening
complications, 516 women with PLTC, and 94 near-miss cases. All of the factors
associated with PLTC and near-miss cases were similar. None of the socio
demographic variables remained significant in the multivariate analysis comparing
different levels of severe morbidity with no complications. Women with no
complications shared similar characteristics with women who experienced non-life
threatening complications. As compared to women who had no complications, women
who had severe morbidity were significantly more likely to have had no antenatal
care. Our results underline the concept that morbidity is a continuum and
indicate that if the underlying causes of poor maternal health outcomes are
addressed, it is likely that changes such as better access to antenatal care will
improve health outcomes across the continuum of morbidity. However, by only
monitoring near-miss cases and mortality, we underestimate the impact on women
who will live with non-life threatening, yet serious maternal morbidities.
PMID- 24347091
TI - The association between physical activity and maternal and neonatal outcomes: a
prospective cohort.
AB - Some evidence, but not enough to be conclusive, suggests that physical activity
in pregnancy reduces the risk of perinatal complications. Our objective was to
examine if physical activity in the year before pregnancy and in the first half
of pregnancy is associated with maternal and neonatal outcomes. Associations
between physical activity and maternal and neonatal outcomes were examined in a
prospective cohort (n = 1,749) in Halifax, Canada. The Kaiser Physical Activity
Survey, completed at approximately 20 weeks' gestation, requested information
regarding physical activity during the year before the pregnancy and the first 20
weeks of pregnancy. Outcomes were assessed by medical chart review. Multiple
logistic regression was used to estimate odds ratios (OR) with 95 % confidence
intervals (CI). Women with prepregnancy physical activity levels in the middle
and highest tertiles were more likely to have high gestational weight gain
relative to women in the lowest tertile [OR (CI): 1.40 (1.06-1.85) and 1.57 (1.18
2.09), respectively]. Higher physical activity in the first half of pregnancy
decreased the odds of delivering a macrosomic infant (p trend = 0.005).
Associations were not observed between total physical activity and gestational
diabetes, gestational hypertension, pre-eclampsia, preterm birth, and low birth
weight. Physical activity before, but not in the first half of pregnancy, is
associated with high gestational weight gain. Physical activity in the first half
of pregnancy may reduce the occurrence of macrosomia without affecting preterm
birth or low birth weight.
PMID- 24347092
TI - Prevalence of overweight among women of childbearing age in Nepal: trends from
2001 to 2011 and associations with socio-demographic factors.
AB - This study examined trends in overweight (body mass index, BMI >= 25.0 kg/m(2))
and underweight (BMI < 18.5 kg/m(2)) from 2001 to 2011 and associations between
socio-demographic factors and overweight in 2011 among 15-49-year-old women in
Nepal. Nationally representative cross-sectional data were used from three
Demographic and Health Surveys conducted in Nepal in 2001 (n = 7,900), 2006 (n =
10,076) and 2011 (n = 5,873). Body weight and height were measured by trained
personnel. Data on socio-demographic variables were obtained by interviewing the
participants. The data were analysed using logistic regression models. The
prevalence of underweight decreased from 26.6 to 18.1 % and the prevalence of
overweight increased from 6.4 to 14.0 % between 2001 and 2011 (p < 0.001 for
both, adjusted for age, parity and education). Both trends were more pronounced
among the rural than the urban women. Although overweight was much more common in
the urban (27.4 %) than in the rural areas (11.8 %) in 2011, the difference
diminished substantially (odds ratio, OR, for being overweight in the urban vs.
in the rural areas, 1.40, 95 % CI 1.15-1.70) when adjusted for other socio
demographic variables. The strongest independent predictors of being overweight
were higher relative wealth and advanced age. Overweight has become almost as
common phenomenon as underweight among women in childbearing age in Nepal. The
urban-rural differences have slightly narrowed and overweight is still related to
a higher socio-economic status in this population. Strategies to prevent further
increases in the prevalence of overweight should urgently be developed and
implemented at all levels of the society.
PMID- 24347093
TI - 3D multi-slab diffusion-weighted readout-segmented EPI with real-time cardiac
reordered K-space acquisition.
AB - PURPOSE: The aim of this study was to develop, implement, and demonstrate a three
dimensional (3D) extension of the readout-segmented echo-planar imaging (rs-EPI)
sequence for diffusion imaging. THEORY AND METHODS: Potential k-space acquisition
schemes were assessed by simulating their associated spatial point spread
functions. Motion-induced phase artifacts were also simulated to test navigator
corrections and a real-time reordering of the k-space acquisition relative to the
cardiac cycle. The cardiac reordering strategy preferentially chooses readout
segments closer to the center of 3D k-space during diastole. Motion-induced phase
artifacts were quantified by calculating the voxel-wise temporal variation in a
set of repeated diffusion-weighted acquisitions. Based on the results of these
simulations, a 2D navigated multi-slab rs-EPI sequence with real-time cardiac
reordering was implemented. The multi-slab implementation enables signal-to-noise
ratio-optimal repetition times of 1-2 s. RESULTS: Cardiac reordering was
validated in simulations and in vivo using the multi-slab rs-EPI sequence. In
comparisons with standard k-space acquisitions, cardiac reordering was shown to
reduce the variability due to motion-induced phase artifacts by 30-50%. High
resolution diffusion tensor imaging data acquired with the cardiac-reordered
multi-slab rs-EPI sequence are presented. CONCLUSION: A 3D multi-slab rs-EPI
sequence with cardiac reordering has been demonstrated in vivo and is shown to
provide high-quality 3D diffusion-weighted data sets.
PMID- 24347095
TI - Dolutegravir: a new integrase strand transfer inhibitor for the treatment of HIV.
AB - The first two integrase strand transfer inhibitors (INSTIs) approved for
treatment of patients infected with human immunodeficiency virus (HIV) were
raltegravir and elvitegravir. Both raltegravir and elvitegravir are now guideline
preferred agents as part of an antiretroviral regimen for treatment-naive
patients. However, raltegravir is dosed twice/day. Elvitegravir is available in a
single-tablet regimen and dosed once/day because it is administered with the
pharmacokinetic booster cobicistat, a potent CYP3A4 inhibitor that can lead to
clinically significant drug-drug interactions. In addition, raltegravir and
elvitegravir have a low genetic barrier to resistance and are associated with
cross-resistance. Dolutegravir is a new-generation INSTI administered once/day
without a pharmacokinetic booster and can be coformulated in a single-tablet
regimen. Phase III studies have demonstrated the efficacy and safety of
dolutegravir for treatment-naive and treatment-experienced patients. Compared
with other INSTIs, dolutegravir has a higher genetic barrier to resistance.
Dolutegravir was approved by the U.S. Food and Drug Administration in August 2013
and joins raltegravir and elvitegravir as guideline-preferred agents for the
management for HIV-infected treatment-naive patients.
PMID- 24347096
TI - Treatment effect of coenzyme Q(10) and an antioxidant cocktail in fibroblasts of
patients with Sanfilippo disease.
AB - Coenzyme Q10 (CoQ10) plays a key role in the exchange of electrons in lysosomal
membrane, which contributes to protons' translocation into the lumen and to the
acidification of intra-lysosomal medium, which is essential for the proteolytic
function of hydrolases responsible -when deficient- of a wide range of inherited
lysosomal diseases such as Sanfilippo syndromes. Our aim was to evaluate whether
treatment with CoQ10 or with an antioxidant cocktail (alpha-tocopherol, N
acetylcysteine and alpha-lipoic acid) were able to ameliorate the biochemical
phenotype in cultured fibroblasts of Sanfilippo patients. Basal CoQ10 was
analyzed in fibroblasts and Sanfilippo A patients showed decreased basal levels.
However, no dysfunction in the CoQ10 biosynthesis pathways was found, revealing
for the first time a secondary CoQ10 deficiency in Sanfilippo A fibroblasts.
Cultured fibroblasts from five patients affected by Sanfilippo A and B diseases
were treated with CoQ10 and an antioxidant cocktail. Upon CoQ10 treatment, none
of the Sanfilippo A fibroblasts increased their residual enzymatic activity, but
the two Sanfilippo B cell lines showed a statistically significant increase of
their residual activity. The antioxidant treatment had no effect on the residual
activity in all tested cell lines. Moreover, one Sanfilippo A and two Sanfilippo
B fibroblasts showed a statistically significant reduction of glycosaminoglycans
accumulation both, after 50 MUmol/L CoQ10 and antioxidant treatment. Fibroblasts
responsive to treatment enhanced their exocytosis levels. Our results are
encouraging as some cellular alterations observed in Sanfilippo syndrome can be
partially restored by CoQ10 or other antioxidant treatment in some patients.
PMID- 24347098
TI - Conflict of interest and evaluation research: should we do effectiveness studies
of our own educational programs?
PMID- 24347097
TI - Optimized breast MRI functional tumor volume as a biomarker of recurrence-free
survival following neoadjuvant chemotherapy.
AB - PURPOSE: To evaluate optimal contrast kinetics thresholds for measuring
functional tumor volume (FTV) by breast magnetic resonance imaging (MRI) for
assessment of recurrence-free survival (RFS). MATERIALS AND METHODS: In this
Institutional Review Board (IRB)-approved retrospective study of 64 patients
(ages 29-72, median age of 48.6) undergoing neoadjuvant chemotherapy (NACT) for
breast cancer, all patients underwent pre-MRI1 and postchemotherapy MRI4 of the
breast. Tumor was defined as voxels meeting thresholds for early percent
enhancement (PEthresh) and early-to-late signal enhancement ratio (SERthresh);
and FTV (PEthresh, SERthresh) by summing all voxels meeting threshold criteria
and minimum connectivity requirements. Ranges of PEthresh from 50% to 220% and
SERthresh from 0.0 to 2.0 were evaluated. A Cox proportional hazard model
determined associations between change in FTV over treatment and RFS at different
PE and SER thresholds. RESULTS: The plot of hazard ratios for change in FTV from
MRI1 to MRI4 showed a broad peak with the maximum hazard ratio and highest
significance occurring at PE threshold of 70% and SER threshold of 1.0 (hazard
ratio = 8.71, 95% confidence interval 2.86-25.5, P < 0.00015), indicating optimal
model fit. CONCLUSION: Enhancement thresholds affect the ability of MRI tumor
volume to predict RFS. The value is robust over a wide range of thresholds,
supporting the use of FTV as a biomarker.
PMID- 24347099
TI - The long-term impact of a performance improvement continuing medical education
intervention on osteoporosis screening.
AB - INTRODUCTION: The purpose of this study is to determine whether a performance
improvement continuing medical education (PI CME) initiative that utilizes
quality improvement (QI) principles is effective in producing sustainable change
in practice to improve the screening of patients at risk for osteoporosis.
METHODOLOGY: A health care center participated in a PI CME program designed to
increase appropriate osteoporosis screening. There were eight 1-hour educational
sessions for this activity over a 9-month period. Thirteen providers completed
all 3 stages of the PI CME program. A variety of other clinicians, in addition to
the 13 providers, participated in the educational sessions. Data were collected
at the beginning and end of the PI CME activity and at three intervals during the
5 years after the completion of the activity. RESULTS: The percentage of tests
for osteoporosis ordered and performed increased significantly from Stage A to
Stage C of the PI CME activity and continued to increase after the completion of
the PI CME activity. Follow-up data at 4 and 40 months (for ordering and
performing osteoporosis screening) and 49 months (for performing the screening
only) reflect the impact of the PI CME activity plus the continuing QI
interventions. The percentage of BMD tests ordered continued to increase
substantially over the post-PI CME periods: 4 and 40 months (F(3,46) = 4.04, p <
.05). Similarly, the percentage of BMD tests performed continued to increase at
4, 40, and 49 months after the conclusion of the PI CME activity (F(4,55) =
12.55, p < .0001). DISCUSSION: The data indicate that PI CME utilizing QI
principles can be effective in producing sustainable change in practice to
improve the screening of patients at risk for osteoporosis. Further research is
needed to determine the extent to which such changes can be directly attributed
to this type of intervention.
PMID- 24347100
TI - How is clinical reasoning developed, maintained, and objectively assessed? Views
from expert internists and internal medicine interns.
AB - INTRODUCTION: There is limited understanding of how clinical reasoning is
developed, maintained, and objectively assessed. Using the theoretical lens of
deliberate practice, we explored physicians' views on clinical reasoning. We
compared responses from internists (faculty) and internal medicine interns, to
identify potential qualitative and/or quantitative differences in how clinical
reasoning is developed and maintained. METHODS: Participants' free-text comments
regarding how clinical reasoning is developed, maintained, and objectively
assessed were analyzed. Three investigators coded responses using a constant
comparative, grounded theory approach. We also compared the frequencies of each
theme between the 2 groups. RESULTS: Twenty-two faculty and 17 interns
participated in this study. Faculty and intern themes for how clinical reasoning
is developed, maintained, and objectively assessed were similar, but quantitative
and qualitative differences emerged. Interrater reliability of themes was high
(overall kappa: 0.92; range: 0.88-0.98). Only experts (faculty) mentioned the
value of teaching for development and maintenance of clinical reasoning. Interns
focused on knowledge acquisition activities and use of online resources. Experts
and intern participants both struggled with how to best measure clinical
reasoning; direct observation was rarely mentioned as a strategy. DISCUSSION:
Consistent with our theoretical expectations, we found quantitative and
qualitative differences in participants' responses, which have implications for
teaching and assessment of clinical reasoning. By capturing the types of
activities and their relative frequencies within and between these groups, this
work adds to the deliberate practice literature.
PMID- 24347101
TI - What do primary care practitioners want to know? A content analysis of questions
asked at the point of care.
AB - INTRODUCTION: Assessing physician needs to develop continuing medical education
(CME) activities is an integral part of CME curriculum development. The purpose
of the present study was to demonstrate the feasibility of identifying areas of
perceived greatest needs for continuing medical education (CME) by using
questions collected electronically at the point of care. METHODS: This study is a
secondary analysis of the "Just-in-Time" (JIT) information librarian consultation
service database of questions using quantitative content analysis methods. The
original JIT project demonstrated the feasibility of a real-time librarian
service for answering questions asked by primary care clinicians at the point of
care using a Web-based platform or handheld device. Data were collected from 88
primary care practitioners in Ontario, Canada, from October 2005 to April 2006.
Questions were answered in less than 15 minutes, enabling clinicians to use the
answer during patient encounters. RESULTS: Description of type and frequency of
questions asked, including the organ system on which the questions focused, was
produced using 2 classification systems, the "taxonomy of generic clinical
questions" (TGCQ), and the International Classification for Primary Care version
2 (ICPC-2). Of the original 1889 questions, 1871 (99.0%) were suitable for
analysis. A total of 970 (52%) of questions related to therapy; of these, 671
(69.2%) addressed questions about drug therapy, representing 36% of all
questions. Questions related to diagnosis (24.8%) and epidemiology (13.5%) were
also common. Organ systems questions concerning musculoskeletal, endocrine, skin,
cardiac, and digestive systems were asked more than other categories. DISCUSSION:
Questions collected at the point of care provide a valuable and unique source of
information on the true learning needs of practicing clinicians. The TGCQ
classification allowed us to show that a majority of questions had to do with
treatment, particularly drug treatment, whereas the use of the ICPC-2
classification illustrated the great variety of questions asked about the diverse
conditions encountered in primary care. It is feasible to use electronically
collected questions asked by primary care clinicians in clinical practice to
categorize self-identified knowledge and practice needs. This could be used to
inform the development of future learning activities.
PMID- 24347102
TI - Improving collaborative care in managing eating disorders: a pilot study.
AB - INTRODUCTION: The purpose of this pilot study was to evaluate the impact of a
continuing interprofessional educational workshop focused on eating disorders in
a rural area in Newfoundland and Labrador (NL), Canada. The pilot study helped
determine if the eating disorder workshop was feasible for implementation to a
broader audience. A conceptual model developed by our eating disorder team and
described in the article guided this innovative program. METHODS: The intensive 2
day workshop was piloted in one community with 41 health and education
professionals in attendance. A key element was the focus on creating and
sustaining collaborative care for eating disorders. Participants completed pre
post workshop measures of interprofessional attitudes and skills, self-reported
knowledge, confidence, and intention to change practice (post questionnaire
only). A 6-month follow-up survey measured self-reported practice change.
RESULTS: There were significant positive changes in interprofessional attitudes
and skills as well as knowledge and confidence in collaborative management of
eating disorders. Post-workshop, 69% (n = 24/35) of participants indicated
intention to change practice, and on follow-up, 7 of 10 respondents reported
implementing changes in practice as a result of the workshop. Low response rate
at follow-up was a limitation. DISCUSSION: Results support the impact of the
workshop in improving knowledge, confidence, and attitudes toward collaboration
and changing practice and the value of implementing the program province-wide.
PMID- 24347103
TI - Preparing culture change agents for academic medicine in a multi-institutional
consortium: the C - change learning action network.
AB - INTRODUCTION: Research suggests an ongoing need for change in the culture of
academic medicine. This article describes the structure, activities and
evaluation of a culture change project: the C - Change Learning Action Network
(LAN) and its impact on participants. The LAN was developed to create the
experience of a culture that would prepare participants to facilitate a culture
in academic medicine that would be more collaborative, inclusive, relational, and
that supports the humanity and vitality of faculty. METHODS: Purposefully diverse
faculty, leaders, and deans from 5 US medical schools convened in 2 1/2-day
meetings biannually over 4 years. LAN meetings employed experiential, cognitive,
and affective learning modes; innovative dialogue strategies; and reflective
practice aimed at facilitating deep dialogue, relationship formation,
collaboration, authenticity, and transformative learning to help members
experience the desired culture. Robust aggregated qualitative and quantitative
data collected from the 5 schools were used to inform and stimulate culture
change plans. RESULTS: Quantitative and qualitative evaluation methods were used.
Participants indicated that a safe, supportive, inclusive, collaborative culture
was established in LAN and highly valued. LAN members reported a deepened
understanding of organizational change, new and valued interpersonal connections,
increased motivation and resilience, new skills and approaches, increased self
awareness and personal growth, emotional connection to the issues of diversity
and inclusion, and application of new learnings in their work. DISCUSSION: A
carefully designed multi-institutional learning community can transform the way
participants experience and view institutional culture. It can motivate and
prepare them to be change agents in their own institutions.
PMID- 24347104
TI - Using an intervention mapping framework to develop an online mental health
continuing education program for pharmacy staff.
AB - INTRODUCTION: Current mental health policy in Australia recognizes that ongoing
mental health workforce development is crucial to mental health care reform.
Community pharmacy staff are well placed to assist people with mental illness
living in the community; however, staff require the knowledge and skills to do
this competently and effectively. This article presents the systematic planning
and development process and content of an education and training program for
community pharmacy staff, using a program planning approach called intervention
mapping. METHODS: The intervention mapping framework was used to guide
development of an online continuing education program. Interviews with mental
health consumers and carers (n = 285) and key stakeholders (n = 15), and a survey
of pharmacy staff (n = 504) informed the needs assessment. Program objectives
were identified specifying required attitudes, knowledge, skills, and confidence.
These objectives were aligned with an education technique and delivery strategy.
This was followed by development of an education program and comprehensive
evaluation plan. The program was piloted face to face with 24 participants and
then translated into an online program comprising eight 30-minute modules for
pharmacists, 4 of which were also used for support staff. The evaluation plan
provided for online participants (n ? 500) to be randomized into intervention
(immediate access) or control groups (delayed training access). It included pre-
and posttraining questionnaires and a reflective learning questionnaire for
pharmacy staff and telephone interviews post pharmacy visit for consumers and
carers. RESULTS: An online education program was developed to address mental
health knowledge, attitudes, confidence, and skills required by pharmacy staff to
work effectively with mental health consumers and carers. DISCUSSION:
Intervention mapping provides a systematic and rigorous approach that can be used
to develop a quality continuing education program for the health workforce.
PMID- 24347106
TI - A community of practice for knowledge translation trainees: an innovative
approach for learning and collaboration.
AB - A growing number of researchers and trainees identify knowledge translation (KT)
as their field of study or practice. Yet, KT educational and professional
development opportunities and established KT networks remain relatively uncommon,
making it challenging for trainees to develop the necessary skills, networks, and
collaborations to optimally work in this area. The Knowledge Translation Trainee
Collaborative is a trainee-initiated and trainee-led community of practice
established by junior knowledge translation researchers and practitioners to:
examine the diversity of knowledge translation research and practice, build
networks with other knowledge translation trainees, and advance the field through
knowledge generation activities. In this article, we describe how the
collaborative serves as an innovative community of practice for continuing
education and professional development in knowledge translation and present a
logic model that provides a framework for designing an evaluation of its impact
as a community of practice. The expectation is that formal and informal
networking will lead to knowledge sharing and knowledge generation opportunities
that improve individual members' competencies (eg, combination of skills,
abilities, and knowledge) in knowledge translation research and practice and
contribute to the development and advancement of the knowledge translation field.
PMID- 24347105
TI - Core competencies for shared decision making training programs: insights from an
international, interdisciplinary working group.
AB - Shared decision making is now making inroads in health care professionals'
continuing education curriculum, but there is no consensus on what core
competencies are required by clinicians for effectively involving patients in
health-related decisions. Ready-made programs for training clinicians in shared
decision making are in high demand, but existing programs vary widely in their
theoretical foundations, length, and content. An international, interdisciplinary
group of 25 individuals met in 2012 to discuss theoretical approaches to making
health-related decisions, compare notes on existing programs, take stock of
stakeholders concerns, and deliberate on core competencies. This article
summarizes the results of those discussions. Some participants believed that
existing models already provide a sufficient conceptual basis for developing and
implementing shared decision making competency-based training programs on a wide
scale. Others argued that this would be premature as there is still no consensus
on the definition of shared decision making or sufficient evidence to recommend
specific competencies for implementing shared decision making. However, all
participants agreed that there were 2 broad types of competencies that clinicians
need for implementing shared decision making: relational competencies and risk
communication competencies. Further multidisciplinary research could broaden and
deepen our understanding of core competencies for shared decision making
training.
PMID- 24347107
TI - Error in formula by Salbach et al.
PMID- 24347108
TI - Reply to Dr. Bland: despite error in formula, EPIC scale still precise.
PMID- 24347109
TI - On the size evolution of monolayer-protected gold clusters during ligand place
exchange reactions: the effect of solvents.
AB - Ligand place-exchange (LPE) reactions are extensively applied for the post
functionalization of monolayer-protected gold clusters (MPCs) by using excessive
incoming ligands to displace initial ones. However, the modified MPCs are often
enlarged or degraded; this results in ill-defined size-dependent properties. The
growth of MPCs essentially involves an unprotected surface that is subsequently
has gold atoms added or is fused with other gold cores owing to collision.
Reported herein is a guideline for the selection of solvents to suppress unwanted
MPC growth. Favorable solvents are those with significant affinity to gold or
with low solubility for desorbed ligands because these properties retard LPE
reactions and minimize the time available for unprotected gold cores. This
finding provides a general and convenient approach to regulate the size of
functionalized MPCs.
PMID- 24347111
TI - Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS
expression as independent biomarker for survival.
AB - Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is
both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in
animal models. We have now studied the clinical implications of TS expression in
gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these
results to other cell cycle biomarker genes. Protein tissue arrays were used to
study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human
GEP-NETs samples. Immunohistochemical expression was correlated with univariate
and multivariate predictors of survival utilizing Kaplan Meier and Cox
proportional hazards models. Real time RT-PCR was used to validate these
findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in
the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6%
and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum
displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression
in GEP-NETs was associated with poorly differentiated endocrine carcinoma,
angiolymphatic invasion, lymph node metastasis and distant metastasis (p < 0.05).
Patients with TS-positive NETs had markedly worse outcomes than TS-negative NETs
as shown by univariate (p < 0.001) and multivariate (p = 0.01) survival analyses.
Expression of p18 predicted survival in TS-positive patients that received
chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent
prognostic biomarker for GEP-NETs. The strong association of increased TS
expression with aggressive disease and early death supports the role of TS as a
cancer promoting agent in these tumors.
PMID- 24347110
TI - Pentalinon andrieuxii root extract is effective in the topical treatment of
cutaneous leishmaniasis caused by Leishmania mexicana.
AB - Cutaneous leishmaniasis (CL) manifests as localized skin lesions, which lead to
significant tissue destruction and disfigurement. In the Yucatan Peninsula, Mayan
traditional healers use Pentalinon andrieuxii Muell.-Arg. (Apocynaceae) roots for
the topical treatment of CL. Here, we studied the effect of P. andrieuxii root
hexane extract (PARE) on the parasites and host cells in vitro and examined its
efficacy in the topical treatment of CL caused by Leishmania mexicana. PARE
exhibited potent antiparasitic activity in vitro against promastigotes as well as
amastigotes residing in macrophages. Electron microscopy of PARE-treated
parasites revealed direct membrane damage. PARE also activated nuclear factor
kappaB and enhanced interferon-gamma receptor and MHC class II expression and TNF
alpha production in macrophages. In addition, PARE induced production of the Th1
promoting cytokine IL-12 in dendritic cells as well as enhanced expression of the
co-stimulatory molecules CD40, CD80, and CD86. In vivo studies showed that L.
mexicana-infected mice treated by topical application of PARE resulted in the
significant reduction in lesion size and parasite burden compared to controls.
These findings indicate that PARE could be used as an alternative therapy for the
topical treatment of CL.
PMID- 24347113
TI - Visual similarity is stronger than semantic similarity in guiding visual search
for numbers.
AB - Using a visual search task, we explored how behavior is influenced by both visual
and semantic information. We recorded participants' eye movements as they
searched for a single target number in a search array of single-digit numbers (0
9). We examined the probability of fixating the various distractors as a function
of two key dimensions: the visual similarity between the target and each
distractor, and the semantic similarity (i.e., the numerical distance) between
the target and each distractor. Visual similarity estimates were obtained using
multidimensional scaling based on the independent observer similarity ratings. A
linear mixed-effects model demonstrated that both visual and semantic similarity
influenced the probability that distractors would be fixated. However, the visual
similarity effect was substantially larger than the semantic similarity effect.
We close by discussing the potential value of using this novel methodological
approach and the implications for both simple and complex visual search displays.
PMID- 24347114
TI - Natural history of five children with surfactant protein C mutations and
interstitial lung disease.
AB - Interstitial lung diseases in infants and children are uncommon and may be caused
by specific inborn errors of surfactant metabolism. Five children with open lung
biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and
evaluated for surfactant protein gene mutations. Four of the children were
originally diagnosed as desquamative interstitial pneumonitis and one as chronic
interstitial pneumonitis. All had good response to chloroquine or
hydroxychloroquine treatment for periods of 7-38 months. Lung function tests,
incremental exercise tests, and rentgenological studies were performed in the
children. Surfactant protein gene mutations were searched in all the patients and
in part of their families. Three of the patients, aged now 32, 29, and 37 years,
feel well and have normal lung function, while two of the patients, both females,
aged 28 and 37 years, conduct normal activities of daily living, have healthy
children but have clinical, physiological and rentgenological evidence of
restrictive lung disease. All five patients were found to have surfactant protein
C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T)
and the other two with new mutations of surfactant protein C gene (p.I38F and
p.V39L). We conclude that detection of surfactant protein mutations should be
attempted in all children presenting with interstitial lung disease. Furthermore,
treatment with hydroxychloroquine should be considered in children with SFTPC
mutations. Prospective evaluation of hydroxychloroquine therapy in a greater
number of patients is needed.
PMID- 24347115
TI - Lessons from fractional flow reserve measurements in chronic total occlusion
interventions.
PMID- 24347116
TI - Sparrow self-expanding sirolimus-eluting stent: do we need a self-expanding
coronary stent?
PMID- 24347117
TI - Conservative management of left main dissection: breaking the taboo.
PMID- 24347118
TI - Transplant coronary atherosclerosis: parallels with in-stent neoatherosclerosis.
PMID- 24347119
TI - Look before (and after) you plug: moving slowly toward safer selection and
management of patients at risk of device erosion.
PMID- 24347120
TI - Arterial access for limb salvage for critical limb ischemia: how low (and how
small) can we go?
PMID- 24347121
TI - Closure for arterial access in balloon aortic valvuloplasty.
PMID- 24347122
TI - Possible synergism of physical exercise and ghrelin-agonists in patients with
cachexia associated with chronic heart failure.
AB - The occurrence of cachexia of multifactorial etiology in chronic heart failure
(CHF) is a common and underestimated condition that usually leads to poor outcome
and low survival rates, with high direct and indirect costs for the Health Care
System. Recently, a consensus definition on cachexia has been reached, leading to
a growing interest by the scientific community in this condition, which
characterizes the last phase of many chronic diseases (i.e., cancer, acquired
immunodeficiency syndrome). The etiology of cachexia is multifactorial and the
underlying pathophysiological mechanisms are essentially the following: anorexia
and malnourishment; immune overactivity and systemic inflammation; and endocrine
disorders (anabolic/catabolic imbalance and resistance to growth hormone). In
this paper, we review the main pathophysiological mechanisms underlying CHF
cachexia, focusing also on the broad spectrum of actions of ghrelin and ghrelin
agonists, and their possible use in combination with physical exercise to
contrast CHF cachexia.
PMID- 24347123
TI - Introducing a multifaceted exercise intervention particular to older adults
diagnosed with Parkinson's disease: a preliminary study.
AB - BACKGROUND AND AIM: With a substantial increase in diagnosed Parkinson's disease,
it is of great importance to examine tolerance and physical measures of evolving
exercise interventions. Of particular importance, a multifaceted exercise
intervention combining active-assisted cycling and resistance training to older
adults diagnosed with Parkinson's disease is being assessed. METHODS: Fourteen
older adults diagnosed with Parkinson's disease and ten healthy older adults
(67.5 +/- 7.9 years of age) engaged in an 8-week, 24-session, multifaceted
exercise protocol. The protocol consisted of both active-assisted cycling and
resistance training. Tolerance was measured, as well as multiple indicators of
health-related physical fitness. These indicators examined improvements in
cardiovascular performance, muscular strength, muscular endurance, and
flexibility. RESULTS: Twenty-two older adults and older adults diagnosed with
Parkinson's disease tolerated the intervention by completing all 24 sessions.
Repeated-measures analysis of variance demonstrated significant (P <= 0.003)
improvements in cardiovascular performance, muscular strength, muscular
endurance, and flexibility for both groups of individuals. DISCUSSION AND
CONCLUSION: The multifaceted intervention is the first to combine both active
assisted cycling and resistance training. The older adult and the older adult
diagnosed with Parkinson's disease exhibited both tolerance and health-related
improvements in physical fitness following the intervention.
PMID- 24347124
TI - Myocardial perfusion imaging: lessons learned and work to be done. By the
Editorial Team of the Journal.
PMID- 24347127
TI - Role of imaging in the diagnosis and management of patients with cardiac
amyloidosis: state of the art review and focus on emerging nuclear techniques.
AB - Amyloidosis is an infiltrative disease characterized by deposition of amyloid
fibrils within the extracellular tissue of one or multiple organs. Involvement of
the heart, cardiac amyloidosis, is recognized as a common cause of restrictive
cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are
cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis
(ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early
recognition of cardiac amyloidosis is of major clinical importance, so is the
ability to differentiate between subtypes. Indeed, both prognosis and therapeutic
options vary drastically depending on the subtype. While endomyocardial biopsy
with immunostaining is considered the gold standard, advances in imaging provide
an attractive non-invasive alternative. Currently, electrocardiography,
echocardiography, and cardiac magnetic resonance imaging are all used in the
evaluation of cardiac amyloidosis with varying diagnostic and prognostic
accuracy. Yet, none of these modalities can effectively differentiate the cardiac
amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used
as bone seeking radioactive tracers, have shown promising results; these
radiotracers selectively bind ATTR, but not AL subtype, and can differentiate
subtypes with high diagnostic accuracy. This review will initially present the
non-radionuclide imaging techniques and then focus on the radionuclide imaging
techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action,
performance and interpretation of the study, diagnostic accuracy, prognostic
value, future clinical perspective, and outlook.
PMID- 24347128
TI - Short and lifetime cardiovascular risk estimates: same wine, different bottles.
Do we have the COURAGE to abandon risk scores?
PMID- 24347129
TI - Correction of proton resonance frequency shift MR-thermometry errors caused by
heat-induced magnetic susceptibility changes during high intensity focused
ultrasound ablations in tissues containing fat.
AB - PURPOSE: In this study, we aim to demonstrate the sensitivity of proton resonance
frequency shift (PRFS) -based thermometry to heat-induced magnetic susceptibility
changes and to present and evaluate a model-based correction procedure. THEORY
AND METHODS: To demonstrate the expected temperature effect, field disturbances
during high intensity focused ultrasound sonications were monitored in breast fat
samples with a three-dimensional (3D) gradient echo sequence. To evaluate the
correction procedure, the interface of tissue-mimicking ethylene glycol gel and
fat was sonicated. During sonication, the temperature was monitored with a 2D
dual flip angle multi-echo gradient echo sequence, allowing for PRFS-based
relative and referenced temperature measurements in the gel and T1 -based
temperature measurements in fat. The PRFS-based measurement in the gel was
corrected by minimizing the discrepancy between the observed 2D temperature
profile and the profile predicted by a 3D thermal model. RESULTS: The HIFU
sonications of breast fat resulted in a magnetic field disturbance which
completely disappeared after cooling. For the correction method, the 5th to 95th
percentile interval of the PRFS-thermometry error in the gel decreased from 3.8
degrees C before correction to 2.0-2.3 degrees C after correction. CONCLUSION:
This study has shown the effects of magnetic susceptibility changes induced by
heating of breast fatty tissue samples. The resultant errors can be reduced by
the use of a model-based correction procedure.
PMID- 24347130
TI - The role of left inferior fronto-occipital fascicle in verbal perseveration: a
brain electrostimulation mapping study.
AB - The subcortical connectivity underlying verbal perseveration (VP) remains poorly
understood. We have previously reported that intraoperative electrical
stimulation of the caudate nucleus during awake surgery resulted in VP. Here, our
purpose is to study the white matter pathway underlying VP using subcortical
stimulation mapping in a series of patients who underwent glioma resection.
Eleven patients with a left hemispheric low grade glioma were operated on while
awake. Intraoperative direct electrical stimulation was used both at cortical and
subcortical levels while the patients carried out motor and naming tasks during
the resection. All patients experienced VP during electrical stimulation
performed at the level of different subcortical locations, which corresponded in
the 11 cases to different parts of the left inferior fronto-occipital fascicle.
Perseveration persisted into the postoperative days, but resolved completely by
three months.Our original findings provide further insight into the
neuroanatomical basis of VP, by supporting the role of left inferior fronto
occipital fascicle. Such data may have both fundamental and clinical
implications.
PMID- 24347131
TI - Retrograde mechanochemical ablation of the small saphenous vein for the treatment
of a venous ulcer.
AB - We present the first case of retrograde ablation of the small saphenous vein to
treat active venous ulceration. A 73-year-old gentleman with complicated varicose
veins of the left leg and a non-healing venous ulcer despite previous successful
endovenous treatment to his left great saphenous vein underwent mechanochemical
ablation of his small saphenous vein with the ClariVein(r) system, under local
anaesthetic, using a retrograde cannulation technique. Post-operatively the
patient had improved symptomatically and the ulcer size had reduced. This report
highlights that patients with small saphenous vein incompetence and active
ulceration can be treated successfully with retrograde mechanochemical ablation.
PMID- 24347132
TI - Causes of successful medico-legal claims following amputation.
AB - INTRODUCTION: The causes of successful medico-legal claims following amputation
were reviewed. METHODS: A retrospective analysis of claims handled by the
National Health Service Litigation Authority, from 2005 to August 2010, was
performed. Under the Freedom of Information Act, the National Health Service
Litigation Authority provided limited details on closed claims, settled with
damages, following a search of their database with the term "amputation." No
demographic data were provided. RESULTS: During this period, 174 claims were
settled by the National Health Service Litigation Authority, who paid out more
than L36.3 million. The causes of the claims were the need for a lower limb
amputation due to a delay in the diagnosis and or treatment of arterial ischaemia
(56), an iatrogenic injury (15), the development of preventable pressure sores
(15), the delay and or failure to diagnose a limb malignancy (6) and the delay in
the management of an infected pseudo-aneurysm (1). Complications following
orthopaedic surgery resulted in 25 successful claims as did the delayed diagnosis
or mismanagement of 10 lower limb fractures. Additional claims followed the
amputation of the wrong toe (1), a retained foreign body (2), an unnecessary
amputation (4), inadequate consent (4), failure to provide thrombo-prophylaxis
following amputation resulting in death (2) and a diathermy burn injury during an
amputation (1). Delay in the diagnosis of and/or failure to manage an injury or
infection resulted in 21 upper limb amputations. There was insufficient
information provided in the remaining 11 claims to determine how the claim
related to an amputation procedure. The largest single payout for damages (L1.9
million) resulted from the failure to diagnose and treat a femoral artery injury
following a road traffic accident leading to an eventual below knee amputation.
CONCLUSION: Delays in the diagnosis and or treatment of arterial ischaemia were
the commonest reasons for a settled claim. Lessons can be learnt from potentially
preventable cases that can be incorporated in medical education and training
programs with the aim of reducing both amputation rates and litigation costs.
PMID- 24347133
TI - Rescue EVAR for ruptured AAA: Clinical success does not mean technical success.
AB - We report a clinical evolution of a 85-years old male admitted to our Emergency
Department for ruptured abdominal aortic aneurysm (rAAA). One month later a huge
type I proximal endoleak was detected and corrected by proximal aortic extension.
We decided to fix the stent-graft to the aortic wall using EndoAnchors. However,
an asymptomatic type III endoleak due to controlateral limb disconnection was
detected at the followed schedulated CT angio and corrected by a relining of the
endograft. The patient is now in good clinical condition with no evidence of
endoleaks at 1-year follow-up.
PMID- 24347134
TI - Median nerve neuropraxia by a large false brachial artery aneurysm.
AB - Peripheral nerve compression is a rare complication of an iatrogenic false
brachial artery aneurysm. We present a 72-year-old patient with median nerve
compression due to a false brachial artery aneurysm after removal of an arterial
catheter. Surgical exclusion of the false aneurysm was performed in order to
release traction of the median nerve. At 3-month assessment, moderate hand
recovery in function and sensibility was noted. In the case of neuropraxia of the
upper extremity, following a history of hospital stay and arterial lining or
catheterization, compression due to pseudoaneurysm should be considered a
probable cause directly at presentation. Early recognition and treatment is
essential to avoid permanent neurological deficit.
PMID- 24347135
TI - Temporal artery biopsy size does not matter.
AB - This study aimed to clarify whether positive temporal artery biopsies had a
greater sample length than negative biopsies in temporal arteritis. It has been
suggested that biopsy length should be at least 1 cm to improve diagnostic
accuracy. A retrospective review of 149 patients who had 151 temporal artery
biopsies was conducted. Twenty biopsies were positive (13.3%), 124 negative
(82.1%) and seven samples were insufficient (4.6%). There was no clinically
significant difference in the mean biopsy size between positive (0.7 cm) and
negative samples (0.65 cm) (t-test: p = .43 NS). Ninety-four patients fulfilled
all three ACR criteria prior to biopsy (62.3%) and four patients (2.6%) changed
ACR score from 2 to 3 after biopsy. Treatment should not be delayed in
anticipation of the biopsy or withheld in the case of a negative biopsy if the
patient's symptoms improve.
PMID- 24347136
TI - Application of endovascular stent placement as a remedy for spontaneous isolated
superior mesenteric artery dissection.
AB - OBJECTIVES: To present our experience regarding endovascular stent placement for
the treatment of spontaneous isolated superior mesenteric artery dissection
(SISMAD) and to evaluate the safety and feasibility of the endovascular therapy.
METHODS: The clinical data from six patients with SISMAD who underwent
endovascular stent placement in two institutions from March 2010 to May 2012 were
analyzed retrospectively. Four patients were implanted a self-expanding stent,
and an additional stent was deployed in two of these patients after the first
stent was implanted. One patient was subjected to a self-expanding stent
implantation combined with coil embolization. The remaining patient underwent
thrombectomy plus partial intimectomy 2 months before a balloon-expandable stent
was implanted. RESULTS: All of the patients recuperated uneventfully without any
reoccurrence of the symptoms in the follow-up period (range 12-38 months).
Contrast-enhanced computer tomography scanning was performed 3 months after the
procedure in all of the patients, and the images showed that the false lumen was
nearly thrombosed and that the true lumen was maintained patent. CONCLUSIONS:
Endovascular stent placement is a simple and safe alternative to aggressive
surgery or uncertain observation.
PMID- 24347137
TI - Hypothenar hammer syndrome and basilic bypass.
AB - We report a case of hypothenar hammer syndrome. The case presents necessary
diagnostic measures and discusses the etiology of this syndrome. Additionally,
the case reviews treatments, which culminated in the eventual use of ulnar artery
bypass with autogenous basilica vein to treat and resolve the ischemic fingers of
the patient.
PMID- 24347138
TI - Primary leiomyosarcoma of saphenous vein presenting as deep venous thrombosis.
AB - Only a small number of venous leiomyosarcomas have been previously reported. Of
these tumors, those of saphenous origin comprise a minority of cases. A 59-year
old man presented with symptoms of deep vein thrombosis and was eventually
diagnosed with primary leiomyosarcoma of great saphenous vein origin. The tumor
was treated with primary resection and femoral vein reconstruction with
autologous patch. Although extremely rare, saphenous leiomyosarcoma can present
as deep vein thrombosis. Vascular tumors should be included in the differential
diagnosis of atypical extremity swelling refractory to conventional deep vein
thrombosis management.
PMID- 24347139
TI - Case Study Interpretation - Fort Lauderdale: Case 1.
PMID- 24347140
TI - Comparison of prescription drug costs in the United States and the United
kingdom, part 4: antibiotics in young children.
AB - OBJECTIVES: To compare the usage and cost of antibiotics in the United States and
United Kingdom in children younger than 10 years. METHODS: A follow up of some
160,000 young children enrolled in U.S. private health insurance companies and an
equal number in general practices in the United Kingdom in 2009, based on two
prospectively designed and documented electronic medical databases. MAIN RESULTS:
Percentage of young children in each country prescribed an antibiotic together
with the estimated total annual cost. PRINCIPAL CONCLUSIONS: In the United
States, ~75% of privately insured children were prescribed one or more
antibiotics compared with an estimated 50% in the United Kingdom. The annual cost
was more than five times higher in the United States compared with the United
Kingdom The usage and cost of antibiotics in young privately insured children is
far higher in the United States than in the United Kingdom, where the government
pays the cost of prescription drugs.
PMID- 24347141
TI - How should propranolol be initiated for infantile hemangiomas: inpatient versus
outpatient?
PMID- 24347142
TI - The Truth, the Whole Truth, and Nothing but the Ground-Truth: Methods to Advance
Environmental Justice and Researcher-Community Partnerships.
AB - Environmental justice advocates often argue that environmental hazards and their
health effects vary by neighborhood, income, and race. To assess these patterns
and advance preventive policy, their colleagues in the research world often use
complex and methodologically sophisticated statistical and geospatial techniques.
One way to bridge the gap between the technical work and the expert knowledge of
local residents is through community-based participatory research strategies. We
document how an environmental justice screening method was coupled with "ground
truthing"-a project in which community members worked with researchers to collect
data across six Los Angeles neighborhoods-which demonstrated the clustering of
potentially hazardous facilities, high levels of air pollution, and elevated
health risks. We discuss recommendations and implications for future research and
collaborations between researchers and community-based organizations.
PMID- 24347143
TI - The Effect of Exposure to Pro-Tobacco Advertising on Experimentation With
Emerging Tobacco Products Among U.S. Adolescents.
AB - INTRODUCTION: This study assessed the influence of exposure to pro-tobacco
advertisements on experimentation with emerging tobacco products among U.S.
adolescents aged >=9 years, in Grades 6 to 12. METHOD: Data were obtained from
the 2011 National Youth Tobacco Survey. Multivariate logistic regression was used
to measure the association between experimentation with snus and e-cigarettes and
exposure to pro-tobacco advertisements from three sources: over the Internet, in
newspapers/magazines, and at retail stores. RESULTS: After controlling for
sociodemographic characteristics and current use of other tobacco products, the
odds of experimenting with snus were 1.36 (95% confidence interval [CI] = 0.88
3.16), 2.03 (95% CI = 1.30-3.17), and 3.24 (95% CI = 2.07-5.07), among students
exposed to one, two, or all three types of pro-tobacco advertisements,
respectively, compared with those exposed to none. Similar results were obtained
for e-cigarettes. CONCLUSION: Stronger restrictions on tobacco advertisements, in
concert with increased tobacco taxes and warning about the dangers of tobacco,
use may help reduce youth tobacco use.
PMID- 24347144
TI - Circles of Care: Implementation and Evaluation of Support Teams for African
Americans With Cancer.
AB - BACKGROUND: Community-based peer support may help meet the practical, emotional,
and spiritual needs of African Americans with advanced cancer. Support teams are
a unique model of peer support for persons facing serious illness, but research
is rare. This study sought to (a) implement new volunteer support teams for
African Americans with advanced cancer in two distinct regions and (b) evaluate
support teams' ability to improve support, awareness of services, and quality of
life for these patients. METHODS: The study used a pre-post design. Community and
academic partners collaborated to implement volunteer support teams and evaluate
the intervention using pre-post surveys of volunteers and patients. Patients who
declined support teams were also interviewed as a comparison group. RESULTS:
Investigators enrolled and trained 130 volunteers who formed 25 support teams in
two geographic regions. Volunteers supported 25 African American patients with
advanced cancer (72%) or other diseases. After 2 months, patients with support
teams reported fewer needs for practical, emotional, and spiritual support on a
structured checklist. They more often communicated with someone about their
cancer care needs (48% vs. 75%, p = .04), and were more aware of Hospice (4% vs.
25%, p = .04), but quality of life scores were unchanged. Comparison patients who
refused a support team had fewer support needs at baseline and follow-up,
suggesting that refusals were based on a lack of need. CONCLUSION: Coordinated
volunteer support teams are a promising new model to provide peer support for
African Americans facing cancer and other serious illnesses. Further testing in a
pragmatic clinical trial is warranted.
PMID- 24347145
TI - Differentiating Behavior Initiation and Maintenance: Theoretical Framework and
Proof of Concept.
AB - Although many interventions are effective for health behavior initiation,
maintenance has proven elusive. Interventions targeting maintenance often extend
the duration with which initiation content is delivered or the duration of follow
up without intervention. We posit that health behavior initiation and maintenance
require separate psychological processes and skills. To determine the value of
operationalizing maintenance as a process separate from initiation, we conducted
a pilot study of a telephone-delivered intervention to assist people in
transitioning from behavior initiation to maintenance. Participants were 20
veterans who had initiated lifestyle changes during a randomized controlled trial
of a cholesterol reduction intervention. After completing the randomized
controlled trial, these participants were enrolled in the pilot maintenance
intervention, which involved three monthly telephone calls from a nurse
interventionist focusing on behavioral maintenance skills. To evaluate the
feasibility and acceptability of this intervention, we assessed recruitment and
retention rates as well as 4-month pre-post changes in health behaviors and
associated psychological processes. We also conducted individual interviews with
participants after study completion. Although not powered to detect significant
changes, there was evidence of improvement in dietary intake and of maintenance
of physical activity and low-density lipoprotein cholesterol during the 4-month
maintenance study. Participants found it helpful to plan for relapses, self
monitor, and obtain social support, but they had mixed reactions about reflecting
on satisfaction with outcomes. Participants accepted the intervention and desired
ongoing contact to maintain accountability. This pilot maintenance intervention
warrants further evaluation in a randomized controlled trial.
PMID- 24347146
TI - Measuring HIV/AIDS-Related Stigma Across South Africa: A Versatile and
Multidimensional Scale.
AB - Reducing HIV/AIDS-related stigma is critical in the fight against HIV/AIDS.
Although national campaigns and prevention programs have been implemented across
South Africa to address this critical concern, assessing the impact of these
initiatives is difficult as it requires that measurement of HIV/AIDS-related
stigma is uniform and comparable nationwide. The appropriateness of existing
stigma measures for this task is unclear as measurement of HIV/AIDS-related
stigma may be qualitatively different across South Africa's diverse population.
The current study assesses a theoretically and culturally informed
multidimensional, HIV/AIDS-related stigma scale for measurement invariance across
a sample drawn from two culturally distinct South African provinces: Limpopo (n =
597) and Western Cape (n = 598). Results suggest measurement invariance across
groups for the HIV/AIDS stigma scale, supporting the scale's integrity and
appropriateness for use across diverse populations.
PMID- 24347147
TI - Help Preferences Among Employees Who Wish to Change Health Behaviors.
AB - OBJECTIVE: To examine the help preferences of employees in the Danish police who
had acknowledged that they wished to change health behaviors. In addition, we
explored whether preferences varied with age, gender, chronic health concerns,
positive expectations of good health, and past experiences of in-house health
promotion services (i.e., wellness service). METHODS: Respondents to an
electronic questionnaire who acknowledged wishing to change health behaviors in
relation to smoking (n = 845), alcohol (n = 684), eating (n = 4,431), and
physical activity (n = 5,179) were asked to choose up to three help alternatives
on a predefined list. RESULTS: In descending order, smokers preferred help from
nicotine gum, no help, and help and support from family and friends. Alcohol
consumers preferred no help or help and support from family and friends or
"other" forms. Employees who wanted to change eating habits preferred a free
fruit bowl, free nutritional guidance, and healthy food at work. Employees who
wanted to change physical activity patterns preferred exercise at work, offers of
free exercise, and exercise in a social/collegial context. CONCLUSION: Wishing to
change health behaviors is not always accompanied by perceiving a need for
assistance. The no-help option was selected fairly frequently and mostly in
relation to alcohol and smoking. A fruit bowl was the most preferred option for
help, followed by exercise at work and free exercise. Help from traditional
health services was ranked low, possibly reflecting that they are primarily
viewed as a solution for stopping disease rather than promoting health.
PMID- 24347148
TI - Diagnostic accuracy of dynamic gadoxetic-acid-enhanced MRI and PET/CT compared in
patients with liver metastases from neuroendocrine neoplasms.
AB - PURPOSE: To evaluate the diagnostic accuracy of dynamic-contrast-enhanced (DCE)
MRI in comparison to both (18)F-FDG- and (68)Ga-DOTATATE-PET/CT in patients with
liver metastases of neuroendocrine neoplasms (NEN). MATERIALS AND METHODS: Thirty
two patients with hepatic metastases from NEN were examined both in DCE-MRI and
positron emission tomography/computed tomography (PET/CT), using either (18)F
fluorodeoxyglucose ((18)F-FDG) or (68)Ga-DOTATATE as tracer. DCE-MRI was
performed at 3 Tesla with Gd-EOB-DTPA acquiring 48 slices every 2.2 s for 5 min.
Three regions of interest (ROIs) representing liver background and liver
metastases were defined in fat-saturated T1w three-dimensional GRE MRI sequences
in the hepatobiliary phase. Corresponding ROIs were then defined in the DCE-MRI-
and in the PET/CT-dataset. Area under the curve (AUC) was calculated for the
differentiation between metastases and liver background for DCE-MRI and PET-CT
parameters. RESULTS: AUC was very high for SUVmean (mean standardized uptake
value) derived from (68)Ga-DOTATATE- (AUC = 0.966), and (18)F-FDG-PET/CT (AUC =
0.989). For DCE-MRI parameters, arterial flow fraction and intracellular uptake
fraction showed the highest AUCs (AUC = 0.826, AUC = 0.819, respectively). The
combination of those two had an AUC of 0.949. The combination of DCE-MRI and PET
CT parameters resulted in the highest AUC. CONCLUSION: Both PET/CT parameters and
DCE-MRI perfusion parameters show a high diagnostic accuracy in the distinction
between liver metastases and liver tissue. Our data suggest that both modalities
provide complementary information.
PMID- 24347149
TI - Evolving health care systems and approaches to maintenance of certification.
PMID- 24347150
TI - Specialty board certification in the United States: issues and evidence.
AB - BACKGROUND: The American Board of Medical Specialties (ABMS) certification and
maintenance of certification (MOC) programs strive to provide the public with
guidance about a physician's competence. This study summarizes the literature on
the effectiveness of these programs. METHOD: A literature search was conducted
for studies published between 1986 and April 2013 and limited to ABMS
certification. A modified version of Kirkpatrick's 4 levels of program evaluation
included the reaction of stakeholders to certification, the extent to which
physicians are encouraged to improve, the relationship between performance in the
programs and nonclinical external measures of physician competence, and the
relationship of performance in the programs with clinical quality measures.
RESULTS: Patients' and hospitals' value of board certification and physician
participation in MOC are high. Physicians are conflicted as to whether the effort
involved is worth its value. Self-reported evidence shows improvement in
knowledge, practice infrastructure, communication with patients and peers, and
clinical care. Certification performance is generally related to nonclinical
external measures such as types of training, practice characteristics,
demographics, and disciplinary actions. In general, physicians who are board
certified provide better patient care, albeit the results have modest effect
sizes and are not unequivocal. CONCLUSIONS: Certification boards should
continuously try to improve their programs in response to feedback from
stakeholders, changes in the way physicians practice, as well as the growth in
the fields of measurement and technology. Keeping pace with these changes in a
responsible and evidence-based way is important.
PMID- 24347151
TI - The Royal College experience and plans for the maintenance of certification
program.
AB - The Royal College of Physicians and Surgeons of Canada, in 2001, implemented a
mandatory maintenance of certification (MOC) program that is required for fellows
to maintain membership and fellowship. Participation in the MOC program is one of
the recognized pathways approved by provincial medical regulatory authorities in
Canada by which specialists can demonstrate their commitment to continued
competent performance in practice. This article traces the historical beginnings
of the MOC program, highlighting the educational foundation and scientific
evidence that influenced its philosophy, goals, and strategic priorities. The MOC
program has evolved into a complex system of continuing professional development
to facilitate and enable a "cultural shift'' in how we conceptualize and support
the continuing professional development (CPD) of specialists. The MOC program is
an educational strategy that supports a learning culture where specialists are
able to design, implement and document their accomplishments from multiple
learning activities to build evidence-informed practices. In the future, the MOC
Program must evolve from assisting fellows to use effective educational resources
"for credit" to enable fellows, leveraging a competency-based CPD model, to
demonstrate their capacity to continuously improve practice. This will require
innovative methods to capture learning and practice improvements in real time,
integrate learning during the delivery of health care, expand automation of
reporting strategies, and facilitate new sociocultural methods of emergent
learning and practice change. Collectively, these directions will require a
research agenda that will generate evidence for how transformative cultural
change in continuing professional education of the profession can be realized.
PMID- 24347152
TI - The United Kingdom's experience with and future plans for revalidation.
AB - Assuring fitness to practice for doctors internationally is increasingly complex.
In the United Kingdom, the General Medical Council (GMC) has recently launched
revalidation, which has been designed to bring all doctors into a governed
environment. Since December 2012, all doctors who wish to practice are required
to submit and reflect on supporting documentation against a framework of best
practice, Good Medical Practice. These documents are brought together in an
annual appraisal. Evidence of practice includes clinical governance activities
such as significant events, complaints and audits, continuing professional
development and feedback from colleagues and patients. Revalidation has been
designed to support professionalism and identify early doctors in difficulty to
support their remediation and so assure patient safety. The appraiser decides
annually if the doctor has met the standard which is shared with the most senior
doctor in the area, the responsible officer (RO). The RO's role is to make a
recommendation for revalidation every 5 years for each doctor to the GMC.
Revalidation is unique in that it is national, compulsory, involves all doctors
regardless of position or training, and is linked to the potentially performance
moderating process of appraisal. However, it has a long and troubled history that
is shaped by high-profile medical scandals and delays from the profession, the
GMC, and the government. Revalidation has been complicated further by rhetoric
around patient care and driving up standards but at the same time identifying
poor performance. The GMC have responded by commissioning a national evaluation
which is currently under development.
PMID- 24347153
TI - Professionalism, career-long assessment, and the American Board of Medical
Specialties' Maintenance of Certification: an introduction to this special
supplement.
PMID- 24347154
TI - Practicing physicians' needs for assessment and feedback as part of professional
development.
AB - Recently, more is being learned about the linkages among assessment, feedback,
and continued learning and professional development. The purpose of this article
is to explore these linkages and to understand how assessment and feedback can
guide professional development and related practice change. It includes a brief
review of conceptual models that guide learning and practice change in general,
related to both formally structured continuing professional development (CPD)
sessions and to self-directed individual activities, and draws on these to inform
learning and change from assessment and feedback. However, evidence and theory
show that using assessment and feedback for learning and change are not naturally
intuitive activities. We propose a 4-phase facilitated reflective process for
enabling engagement with assessment data and feedback and using it for learning
and change, and explore the varied personal and contextual factors which are
influential and require consideration. We end with practical implications and
suggestions.
PMID- 24347155
TI - Maintenance of certification, revalidation, and professional self-regulation.
PMID- 24347156
TI - American Board of Medical Specialties Maintenance of Certification: theory and
evidence regarding the current framework.
AB - The American Board of Medical Specialties Maintenance of Certification Program
(ABMS MOC) is designed to provide a comprehensive approach to physician lifelong
learning, self-assessment, and quality improvement (QI) through its 4-part
framework and coverage of the 6 competencies previously adopted by the ABMS and
the Accreditation Council for Graduate Medical Education (ACGME). In this
article, the theoretical rationale and exemplary empiric data regarding the MOC
program and its individual parts are reviewed. The value of each part is
considered in relation to 4 criteria about the relationship of the competencies
addressed within that part to (1) patient outcomes, (2) physician performance,
(3) validity of the assessment or educational methods utilized, and (4) learning
or improvement potential. Overall, a sound theoretical rationale and a
respectable evidence base exists to support the current structure and elements of
the MOC program. However, it is incumbent on the ABMS and ABMS member boards to
continue to examine their programs moving forward to assure the public and the
profession that they are meeting expectations, are clinically relevant, and
provide value to patients and participating physicians, and to refine and improve
them as ongoing research indicates.
PMID- 24347157
TI - An overview of plant volatile metabolomics, sample treatment and reporting
considerations with emphasis on mechanical damage and biological control of
weeds.
AB - INTRODUCTION: The technology for the collection and analysis of plant-emitted
volatiles for understanding chemical cues of plant-plant, plant-insect or plant
microbe interactions has increased over the years. Consequently, the in situ
collection, analysis and identification of volatiles are considered integral to
elucidation of complex plant communications. Due to the complexity and range of
emissions the conditions for consistent emission of volatiles are difficult to
standardise. OBJECTIVE: To discuss: evaluation of emitted volatile metabolites as
a means of screening potential target- and non-target weeds/plants for insect
biological control agents; plant volatile metabolomics to analyse resultant data;
importance of considering volatiles from damaged plants; and use of a database
for reporting experimental conditions and results. METHOD: Recent literature
relating to plant volatiles and plant volatile metabolomics are summarised to
provide a basic understanding of how metabolomics can be applied to the study of
plant volatiles. RESULTS: An overview of plant secondary metabolites, plant
volatile metabolomics, analysis of plant volatile metabolomics data and the
subsequent input into a database, the roles of plant volatiles, volatile emission
as a function of treatment, and the application of plant volatile metabolomics to
biological control of invasive weeds. CONCLUSION: It is recommended that in
addition to a non-damaged treatment, plants be damaged prior to collecting
volatiles to provide the greatest diversity of odours. For the model system
provided, optimal volatile emission occurred when the leaf was punctured with a
needle. Results stored in a database should include basic environmental
conditions or treatments.
PMID- 24347158
TI - Biogas plasticization coupled anaerobic digestion: the anaerobic pump
stoichiometry.
AB - This paper presents the stoichiometry section of a bioenergetics investigation
into the biogas plasticization of wastewater sludge using the Anaerobic Pump
(TAP). Three residue samples, an input substrate and two residual products, were
collected from two side by side operated AD systems, a conventional continuous
flow and stirred reactor, and TAP, and submitted for elemental and calorimetric
analyses. The elemental compositions of the residues were fitted to a
heterotrophic metabolism model [1] for both systems. To facilitate balanced
stoichiometric models, a simple "cell" correction computation separates measured
residual composites into "real" residual composition and cell growth (C5H7NO2)
components. The elemental data and model results show that the TAP stage II
residual composition (C1H0.065O0.0027N0.036) was nearly devoid of hydrogen and
oxygen, leaving only fixed carbon and cells grown as the composition of the
remaining mass. This quantitative evidence supports prior measurements of very
high methane yields from TAP stage II reactor during steady-state experiments
[2]. All performance parameters derived from the stoichiometric model(s) showed
good agreement with measured steady-state averaged values. These findings are
strong evidence that plasticization-disruption (TAP) cycle is the mechanism
responsible for the observed increases in methane yield. The accuracy achieved by
the stoichiometry models qualifies them for thermodynamic analysis to obtain
potentials and bioconversion efficiencies. How applied pressure causes matrix
conformation changes triggered by a functional consequence (plasticization and
disruption) is this study's essential focus.
PMID- 24347159
TI - Aqueous extract of Crataegus azarolus protects against DNA damage in human
lymphoblast Cell K562 and enhances antioxidant activity.
AB - The present study was carried out to characterize the cellular antioxidant effect
of the aqueous extract of Crataegus azarolus and its antigenotoxic potential
using human myelogenous cells, K562. The antioxidant capacity of this extract was
evaluated by determining its cellular antioxidant activity (CAA) in K562 cells.
Also, preceding antigenotoxicity assessment, its eventual genotoxicity property
was investigated by evaluating its capacity to induce the DNA degradation of
treated cell nuclei. As no genotoxicity was detected at different exposure times,
its ability to protect cell DNA against H2O2 oxidative effect was investigated,
using the "comet assay." It appears that 800 MUg/mL of extract inhibited the
genotoxicity induced by H2O2 with a rate of 41.30 %, after 4 h of incubation. In
addition, this extract revealed a significant cellular antioxidant capacity
against the reactive oxygen species in K562 cells.
PMID- 24347160
TI - Influence of forced internal air circulation on airflow distribution and heat
transfer in a gas double-dynamic solid-state fermentation bioreactor.
AB - Internal air circulation affects the temperature field distribution in a gas
double-dynamic solid-state fermentation bioreactor (GDSFB). To enhance heat
transfer through strengthening internal air circulation in a GDSFB, we put an air
distribution plate (ADP) into the bioreactor and studied the effects of forced
internal air circulation on airflow, heat transfer, and cellulase activity of
Trichoderma viride L3. Results showed that ADP could help form a steady and
uniform airflow distribution, and with gas-guide tubes, air reversal was formed
inside the bioreactor, thus resulting in a smaller temperature difference between
medium and air by enhancing convective heat transfer inside the bioreactor. Using
an ADP of 5.35 % aperture ratio caused a 1 degrees C decrease in the average
temperature difference during the solid-state fermentation process of T. viride
L3. Meanwhile, the cellulase activity of T. viride L3 increased by 13.5 %. The
best heat-transfer effect was attained when using an ADP of 5.35 % aperture ratio
and setting the fan power to 125 V (4.81 W) in the gas double-dynamic solid-state
fermentation (GDSF) process. An option of suitable aperture ratio and fan power
may be conducive to ADPs' industrial amplification.
PMID- 24347161
TI - Characterization and high level expression of acidic endoglucanase in Pichia
pastoris.
AB - Bioconversion of cellulosic material into glucose needs cellulase enzymes. One of
the most important organisms that produces cellulases is Trichoderma reesei,
whose cellulose enzymes are probably the most widely used in the industry.
However, these enzymes are not stable enough at high pH and temperatures. The
optimized synthetic endoglucanase II gene with Pichia pastoris codon preferences
was secretary expressed in P. pastoris. Recombinant enzyme characterization
showed maximum activity at pH 4.8 and temperature 75 degrees C, and it
demonstrated increasing thermal stability in high temperature. The enzyme
maintained its activity in a wide pH range from 3.5 to 6.5. The optimization of
fermentation medium was carried out in shaking flasks. Recombinant protein
expression at optimum conditions (pH 7, temperature 25 degrees C, and 1 %
methanol induction) for 72 h demonstrated 2,358.8 U/ml endoglucanase activity
units. To our knowledge, this is the highest acidic thermophilic endoglucanase
activity that is reported in crude intracellular medium in P. pastoris. We
conclude that P. pastoris is an appropriate host for high-level expression of
optimized endoglucanase gene with improved thermal stability.
PMID- 24347162
TI - Effects of isoflurane anesthesia on F-waves in the sciatic nerve of the adult
rat.
AB - INTRODUCTION: Nerve conduction studies provide insights into the functional
consequences of axonal and myelin pathology in peripheral neuropathies. We
investigated whether isoflurane inhalation anesthesia alters F-wave latencies and
F-persistence in the sciatic nerve of adult rats. METHODS: Ten rats were
investigated at 3 different isoflurane concentrations followed by ketamine
xylazine injection anesthesia. To assess F-wave latencies, a stimulation paradigm
was chosen to minimize H-reflex masking of F-waves. RESULTS: F-wave persistence
rates were reduced with 3.5% isoflurane concentration at 4 and 10 Hz supramaximal
stimulation and marginally reduced with 2.5% isoflurane when compared with
ketamine-xylazine. F-wave amplitudes decreased progressively with rising stimulus
frequency in all types of anesthesia and most at 3.5% isoflurane concentration.
CONCLUSIONS: The type of anesthesia and the stimulus repetition rate have an
impact on some F-wave parameters. Higher isoflurane concentrations and repetition
rates are not recommended in experimental studies using rat neuropathy models
where F-waves are of interest.
PMID- 24347163
TI - Competition through dimerization between antiapoptotic and proapoptotic HS-1
associated protein X-1 (Hax-1).
AB - Studies on Hax-1 have mainly focused on variant (v) 1, demonstrating its
antiapoptotic properties. However, HAX1 is heavily spliced, generating
structurally distinct isoforms. We sought to characterize the Hax-1 isoforms
expressed in rat heart before and after insult. We confirmed the presence of at
least four Hax-1 transcripts in healthy rat cardiac muscle. These exhibited
differential expression before and after induction of myocardial infarction, with
v2 being up-regulated 12-fold at the transcript level and 1.5-fold at the protein
level post-insult. Contrary to antiapoptotic rat and human v1, overexpression of
rat v2 or human v4 (the human homologue of rat v2) in epithelial cells
exacerbated cell death by 30% following H2O2 treatment compared with control
vector. Coexpression of rat v1 and v2 or human v1 and v4 neutralized the
protective effects of rat and human v1 and the proapoptotic effects of rat v2 and
human v4 by modulating cytochrome c release. This is, at least partly, mediated
by the ability of Hax-1 proteins to form homotypic and heterotypic dimers with
binding affinities ranging from ~3.8 nm for v1 dimers to ~97 nm for v1/v2 dimers.
The minimal binding region supporting these interactions lies between amino acids
97-278, which are shared by nearly all Hax-1 proteins, indicating that additional
factors regulate the preferential formation of Hax-1 homo- or heterodimers. Our
studies are the first to show that Hax-1 is a family of anti- and proapoptotic
regulators that may modulate cell survival and death through homo- or
heterodimerization.
PMID- 24347164
TI - Structural change in FtsZ Induced by intermolecular interactions between bound
GTP and the T7 loop.
AB - FtsZ is a prokaryotic homolog of tubulin and is a key molecule in bacterial cell
division. FtsZ with bound GTP polymerizes into tubulin-like protofilaments. Upon
polymerization, the T7 loop of one subunit is inserted into the nucleotide
binding pocket of the second subunit, which results in GTP hydrolysis. Thus, the
T7 loop is important for both polymerization and hydrolysis in the tubulin/FtsZ
family. Although x-ray crystallography revealed both straight and curved
conformations of tubulin, only a curved structure was known for FtsZ. Recently,
however, FtsZ from Staphylococcus aureus has been shown to have a very different
conformation from the canonical FtsZ structure. The present study was performed
to investigate the structure of FtsZ from Staphylococcus aureus by mutagenesis
experiments; the effects of amino acid changes in the T7 loop on the structure as
well as on GTPase activity were studied. These analyses indicated that FtsZ
changes its conformation suitable for polymerization and GTP hydrolysis by
movement between N- and C-subdomains via intermolecular interactions between
bound nucleotide and residues in the T7 loop.
PMID- 24347165
TI - Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-beta
signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung
fibroblasts.
AB - Glucocorticoids represent the mainstay therapy for many lung diseases, providing
outstanding management of asthma but performing surprisingly poorly in patients
with acute respiratory distress syndrome, chronic obstructive pulmonary disease,
lung fibrosis, and blunted lung development associated with bronchopulmonary
dysplasia in preterm infants. TGF-beta is a pathogenic mediator of all four of
these diseases, prompting us to explore glucocorticoid/TGF-beta signaling cross
talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide,
and fluticasone, potentiated TGF-beta signaling by the Acvrl1/Smad1/5/8 signaling
axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well
as primary lung fibroblasts, smooth muscle cells, and endothelial cells.
Dexamethasone drove expression of the accessory type III TGF-beta receptor
Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a "switch" that
blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung
fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was
active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling.
Dexamethasone acted synergistically with TGF-beta to drive differentiation of
primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth
muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent
processes in fibroblasts. Administration of dexamethasone to live mice
recapitulated these observations and revealed a lung-specific impact of
dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These
data point to an interesting and hitherto unknown impact of glucocorticoids on
TGF-beta signaling in lung fibroblasts and other constituent cell types of the
lung that may be relevant to lung physiology, as well as lung pathophysiology, in
terms of drug/disease interactions.
PMID- 24347166
TI - Crucial positively charged residues for ligand activation of the GPR35 receptor.
AB - GPR35 is a G protein-coupled receptor expressed in the immune, gastrointestinal,
and nervous systems in gastric carcinomas and is implicated in heart failure and
pain perception. We investigated residues in GPR35 responsible for ligand
activation and the receptor structure in the active state. GPR35 contains
numerous positively charged amino acids that face into the binding pocket that
cluster in two distinct receptor regions, TMH3-4-5-6 and TMH1-2-7. Computer
modeling implicated TMH3-4-5-6 for activation by the GPR35 agonists zaprinast and
pamoic acid. Mutation results for the TMH1-2-7 region of GPR35 showed no change
in ligand efficacies at the K1.32A, R2.65A, R7.33A, and K7.40A mutants. However,
mutation of arginine residues in the TMH3-4-5-6 region (R4.60, R6.58, R3.36,
R(164), and R(167) in the EC2 loop) had effects on signaling for one or both
agonists tested. R4.60A resulted in a total ablation of agonist-induced
activation in both the beta-arrestin trafficking and ERK1/2 activation assays.
R6.58A increased the potency of zaprinast 30-fold in the pERK assay. The R(167)A
mutant decreased the potency of pamoic acid in the beta-arrestin trafficking
assay. The R(164)A and R(164)L mutants decreased potencies of both agonists.
Similar trends for R6.58A and R(167)A were observed in calcium responses.
Computer modeling showed that the R6.58A mutant has additional interactions with
zaprinast. R3.36A did not express on the cell surface but was trapped in the
cytoplasm. The lack of surface expression of R3.36A was rescued by a GPR35
antagonist, CID2745687. These results clearly show that R4.60, R(164), R(167),
and R6.58 play crucial roles in the agonist initiated activation of GPR35.
PMID- 24347167
TI - Bidirectional control of postsynaptic density-95 (PSD-95) clustering by
Huntingtin.
AB - Huntington disease is associated with early alterations in corticostriatal
synaptic function that precede cell death, and it is postulated that ameliorating
such changes may delay clinical onset and/or prevent neurodegeneration. Although
many of these synaptic alterations are thought to be attributable to a toxic gain
of function of the mutant huntingtin protein, the role that nonpathogenic
huntingtin (HTT) plays in synaptic function is relatively unexplored. Here, we
compare the immunocytochemical localization of a major postsynaptic scaffolding
protein, PSD-95, in striatal neurons from WT mice and mice overexpressing HTT
with 18 glutamine repeats (YAC18, nonpathogenic). We found that HTT
overexpression resulted in a palmitoylation- and BDNF-dependent increase in PSD
95 clustering at synaptic sites in striatal spiny projection neurons (SPNs) co
cultured with cortical neurons. Surprisingly, the latter effect was mediated
presynaptically, as HTT overexpression in cortical neurons alone was sufficient
to increase PSD-95 clustering in the postsynaptic SPNs. In contrast, antisense
oligonucleotide knockdown of HTT in WT co-cultures resulted in a significant
reduction of PSD-95 clustering in SPNs. Notably, despite these bidirectional
changes in PSD-95 clustering, we did not observe an alteration in basal
electrophysiological measures of AMPA and NMDA receptors. Thus, unlike in
previous studies in the hippocampus, enhanced or decreased PSD-95 clustering
alone was insufficient to drive AMPA or NMDA receptors into or out of SPN
synapses. In all, our results demonstrate that nonpathogenic HTT can indeed
influence synaptic protein localization and uncover a novel role of HTT in PSD-95
distribution.
PMID- 24347168
TI - Endoplasmic reticulum (ER) stress and hypoxia response pathways interact to
potentiate hypoxia-inducible factor 1 (HIF-1) transcriptional activity on targets
like vascular endothelial growth factor (VEGF).
AB - Cells respond to suboptimal microenvironments by activating stress signaling
pathways, like the unfolded protein response and hypoxia-induced transcription
factors HIF-1/2, to restore homeostasis. Both cytoprotective pathways have been
well studied in isolation at the biochemical and molecular levels. Mounting
evidence reveals that they can be activated simultaneously in tumor cells and,
likely, in other tissues experiencing inadequate microenvironments and that they
share some transcriptional targets, like the proangiogenic factor VEGFA. However,
the potential interaction between these pathways is poorly understood. Cell
culture experiments revealed that as a consequence of unfolded protein response
activation, ATF4 bound to the human VEGFA promoter and activated its
transcription, whereas HIF-1 did so in response to hypoxia. When both pathways
were activated together, VEGFA transcripts were induced to a higher level than
when either stress was applied alone. Surprisingly, this was not due to the
combined actions of the stress pathway-specific transcription factors. Instead,
we found that endoplasmic reticulum stress potentiated HIF-1 activity to
transactivate VEGF expression as well as another well characterized target,
BNIP3. These data reveal an unexpected interaction between two important
cytoprotective responses that are likely to have significant consequences in
environmentally compromised tissues and tumor cells.
PMID- 24347169
TI - Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune
encephalomyelitis in mice.
AB - Ninjurin1 is a homotypic adhesion molecule that contributes to leukocyte
trafficking in experimental autoimmune encephalomyelitis (EAE), an animal model
of multiple sclerosis. However, in vivo gene deficiency animal studies have not
yet been done. Here, we constructed Ninjurin1 knock-out (KO) mice and
investigated the role of Ninjurin1 on leukocyte trafficking under inflammation
conditions such as EAE and endotoxin-induced uveitis. Ninjurin1 KO mice
attenuated EAE susceptibility by reducing leukocyte recruitment into the injury
regions of the spinal cord and showed less adhesion of leukocytes on inflamed
retinal vessels in endotoxin-induced uveitis mice. Moreover, the administration
of a custom-made antibody (Ab26-37) targeting the Ninjurin1 binding domain
ameliorated the EAE symptoms, showing the contribution of its adhesion activity
to leukocyte trafficking. In addition, we addressed the transendothelial
migration (TEM) activity of bone marrow-derived macrophages and Raw264.7 cells
according to the expression level of Ninjurin1. TEM activity was decreased in
Ninjurin1 KO bone marrow-derived macrophages and siNinj1 Raw264.7 cells.
Consistent with this, GFP-tagged mNinj1-overexpressing Raw264.7 cells increased
their TEM activity. Taken together, we have clarified the contribution of
Ninjurin1 to leukocyte trafficking in vivo and delineated its direct functions to
TEM, emphasizing Ninjurin1 as a beneficial therapeutic target against
inflammatory diseases such as multiple sclerosis.
PMID- 24347170
TI - Ascorbate efflux as a new strategy for iron reduction and transport in plants.
AB - Iron (Fe) is essential for virtually all living organisms. The identification of
the chemical forms of iron (the speciation) circulating in and between cells is
crucial to further understand the mechanisms of iron delivery to its final
targets. Here we analyzed how iron is transported to the seeds by the chemical
identification of iron complexes that are delivered to embryos, followed by the
biochemical characterization of the transport of these complexes by the embryo,
using the pea (Pisum sativum) as a model species. We have found that iron
circulates as ferric complexes with citrate and malate (Fe(III)3Cit2Mal2,
Fe(III)3Cit3Mal1, Fe(III)Cit2). Because dicotyledonous plants only transport
ferrous iron, we checked whether embryos were capable of reducing iron of these
complexes. Indeed, embryos did express a constitutively high ferric reduction
activity. Surprisingly, iron(III) reduction is not catalyzed by the expected
membrane-bound ferric reductase. Instead, embryos efflux high amounts of
ascorbate that chemically reduce iron(III) from citrate-malate complexes. In
vitro transport experiments on isolated embryos using radiolabeled (55)Fe
demonstrated that this ascorbate-mediated reduction is an obligatory step for the
uptake of iron(II). Moreover, the ascorbate efflux activity was also measured in
Arabidopsis embryos, suggesting that this new iron transport system may be
generic to dicotyledonous plants. Finally, in embryos of the ascorbate-deficient
mutants vtc2-4, vtc5-1, and vtc5-2, the reducing activity and the iron
concentration were reduced significantly. Taken together, our results identified
a new iron transport mechanism in plants that could play a major role to control
iron loading in seeds.
PMID- 24347171
TI - The death-inducer obliterator 1 (Dido1) gene regulates embryonic stem cell self
renewal.
AB - The regulatory network of factors that center on master transcription factors
such as Oct4, Nanog, and Sox2 help maintain embryonic stem (ES) cells and ensure
their pluripotency. The target genes of these master transcription factors define
the ES cell transcriptional landscape. In this study, we report our findings that
Dido1, a target of canonical transcription factors such as Oct4, Sox2, and Nanog,
plays an important role in regulating ES cell maintenance. We found that
depletion of Dido1 in mouse ES cells led to differentiation, and ectopic
expression of Dido1 inhibited differentiation induced by leukemia inhibitory
factor withdrawal. We further demonstrated that whereas Nanog and Oct4 could
occupy the Dido1 locus and promote its transcription, Dido1 could also target to
the loci of pluripotency factors such as Nanog and Oct4 and positively regulate
their expression. Through this feedback and feedforward loop, Dido1 is able to
regulate self-renewal of mouse ES cells.
PMID- 24347172
TI - The reverse gyrase from Pyrobaculum calidifontis, a novel extremely thermophilic
DNA topoisomerase endowed with DNA unwinding and annealing activities.
AB - Reverse gyrase is a DNA topoisomerase specific for hyperthermophilic bacteria and
archaea. It catalyzes the peculiar ATP-dependent DNA-positive supercoiling
reaction and might be involved in the physiological adaptation to high growth
temperature. Reverse gyrase comprises an N-terminal ATPase and a C-terminal
topoisomerase domain, which cooperate in enzyme activity, but details of its
mechanism of action are still not clear. We present here a functional
characterization of PcalRG, a novel reverse gyrase from the archaeon Pyrobaculum
calidifontis. PcalRG is the most robust and processive reverse gyrase known to
date; it is active over a wide range of conditions, including temperature, ionic
strength, and ATP concentration. Moreover, it holds a strong ATP-inhibited DNA
cleavage activity. Most important, PcalRG is able to induce ATP-dependent
unwinding of synthetic Holliday junctions and ATP-stimulated annealing of
unconstrained single-stranded oligonucleotides. Combined DNA unwinding and
annealing activities are typical of certain helicases, but until now were shown
for no other reverse gyrase. Our results suggest for the first time that a
reverse gyrase shares not only structural but also functional features with
evolutionary conserved helicase-topoisomerase complexes involved in genome
stability.
PMID- 24347173
TI - Fluorine-doped Fe(2)O(3) as high energy density electroactive material for hybrid
supercapacitor applications.
AB - Nanostructured alpha-Fe2 O3 with and without fluorine substitution were
successfully obtained by a green route, that is, microwave irradiation. The
hematite phase materials were evaluated as a high-performance electrode material
in a hybrid supercapacitor configuration along with activated carbon (AC). The
presence of fluorine was confirmed through X-ray photoelectron spectroscopy and
transmission electron microscopy. Fluorine-doped Fe2 O3 (F-Fe2 O3 ) exhibits an
enhanced pseudocapacitive performance compared to that of the bare hematite
phase. The F-Fe2 O3 /AC cell delivered a specific capacitance of 71 F g(-1) at a
current density of 2.25 A g(-1) and retained approximately 90 % of its initial
capacitance after 15 000 cycles. Furthermore, the F-Fe2 O3 /AC cell showed a very
high energy density of about 28 W h kg(-1) compared to bare hematite phase (~9 W
h kg(-1) ). These data clearly reveal that the electrochemical performance of Fe2
O3 can be improved by fluorine doping, thereby dramatically improving the energy
density of the system.
PMID- 24347174
TI - Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify
novel biomarkers of proinflammation in patients with type 2 diabetes.
AB - Emerging data indicate that gut-derived endotoxin (metabolic endotoxemia) may
contribute to low-grade systemic inflammation in insulin-resistant states.
Specific gut bacteria seem to serve as lipopolysaccharide (LPS) sources and
several reports claim a role for increased intestinal permeability in the genesis
of metabolic disorders. Therefore, we investigated the serum levels of LPS and
zonulin (ZO-1, a marker of gut permeability) along with systemic levels of tumor
necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) in patients with type
2 diabetes mellitus (T2DM) compared to control subjects. Study subjects were
recruited from the Chennai Urban Rural Epidemiology Study [CURES], Chennai,
India. Study group (n = 45 each) comprised of a) subjects with normal glucose
tolerance (NGT) and (b) patients with T2DM. LPS, ZO-1, TNF-alpha, and IL-6 levels
were measured by ELISA. Serum levels of LPS [p < 0.05], LPS activity [p < 0.001],
ZO-1 [p < 0.001], TNFalpha [p < 0.001], and IL-6 [p < 0.001] were significantly
increased in patients with T2DM compared to control subjects. Pearson correlation
analysis revealed that LPS activity was significantly and positively correlated
with ZO-1, fasting plasma glucose, 2 h post glucose, HbA1c, serum triglycerides,
TNF-alpha, IL-6, and negatively correlated with HDL cholesterol. Regression
analysis showed that increased LPS levels were significantly associated with type
2 diabetes [odds ratio (OR) 13.43, 95 % CI 1.998-18.9; p = 0.003]. In Asian
Indians who are considered highly insulin resistant, the circulatory LPS levels,
LPS activity, and ZO-1 were significantly increased in patients with type 2
diabetes and showed positive correlation with inflammatory markers and poor
glycemic/lipid control.
PMID- 24347175
TI - Effects of gamma-irradiation on Na,K-ATPase in cardiac sarcolemma.
AB - Previous studies showed that adverse effect of ionizing radiation on the
cardiovascular system is beside other factors mostly mediated by reactive oxygen
and nitrogen species, which deplete antioxidant stores. One of the structures
highly sensitive to radicals is the Na,K-ATPase the main system responsible for
extrusion of superfluous Na(+) out of the cell which utilizes the energy derived
from ATP. The aim of present study was the investigation of functional properties
of cardiac Na,K-ATPase in 20-week-old male rats 6 weeks after gamma-irradiation
by a dose 25 Gy (IR). Irradiation induced decrease of systolic blood pressure
from 133 in controls to 85 mmHg in IR group together with hypertrophy of right
ventricle (RV) and hypotrophy of left ventricle (LV). When activating the cardiac
Na,K-ATPase with substrate, its activity was lower in IR in the whole
concentration range of ATP. Evaluation of kinetic parameters revealed a decrease
of the maximum velocity (V max) by 40 % with no changes in the value of Michaelis
Menten constant (K m). During activation with Na(+), we observed a decrease of
the enzyme activity in hearts from IR at all tested Na(+) concentrations. The
value of V max decreased by 38 %, and the concentration of Na(+) that gives half
maximal reaction velocity (K Na) increased by 62 %. This impairment in the
affinity of the Na(+)-binding site together with decreased number of active Na,K
ATPase molecules, as indicated by lowered V max values, are probably responsible
for the deteriorated efflux of the excessive Na(+) from the intracellular space
in hearts of irradiated rats.
PMID- 24347176
TI - Mitigation of postischemic cardiac contractile dysfunction by CaMKII inhibition:
effects on programmed necrotic and apoptotic cell death.
AB - While Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been suggested
to be an important protein regulating heart function upon ischemia/reperfusion
(I/R), the mechanisms responsible are not fully known. Furthermore, it is not
known whether CaMKII activation can modulate necroptosis, a recently described
form of programmed cell death. In order to investigate these issues, Langendroff
perfused rat hearts were subjected to global ischemia and reperfusion, and CaMKII
inhibition was achieved by adding the CaMKII inhibitor KN-93 (0.5 MUmol/dm(3)) to
the perfusion solution before the induction of ischemia. Immunoblotting was used
to detect changes in expression of proteins modulating both necroptotic and
apoptotic cell death. CaMKII inhibition normalized I/R induced increases in
expression of necroptotic RIP1 and caspase-8 along with proteins of the intrinsic
apoptotic pathway, namely cytochrome c and caspase-9. In addition, it increased
the Bcl-2/Bax ratio and reduced caspase-3 and cleaved PARP1 content suggesting
reduction of cell death. These changes coexisted with improvement of postischemic
contractile function. On the other hand, there was no correlation between levels
of pT287-CaMKIIdelta and LVDP recovery after I/R. These results demonstrate for
the first time that CaMKII inhibition may mitigate cardiac contractile
dysfunction, at least partially, by limiting the contents of not only apoptotic,
but also necroptotic proteins. Phosphorylation of CaMKII seems unlikely to
determine the degree of postischemic recovery of contractile function.
PMID- 24347177
TI - The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and
IL-15 in Hela cells.
AB - Toll-like receptors (TLRs) play important roles in activation of immunoreaction
and tumor development. Toll-like receptor 7 (TLR7), one of the TLRs binding with
single-stranded RNA, activates intracellular pathways and stimulates the release
of proinflammatory cytokines, chemokines. In this study, we investigated the
impact of the TLR7-signaling pathway on the expression of vascular endothelial
growth factor (VEGF), matrix metalloproteinase 2 (MMP2), tissue inhibitor of
metalloproteinase 1 (TIMP1), interleukin 6 (IL-6), and interleukin 15 (IL-15),
which have been testified to refer to the immunomodulating and tumor progression.
We confirmed that the TLR7 was expressed by Hela cells, despite the abundance was
weak. Gardiquimod, one of the TLR7 ligands, can promote these five genes
expression in varying degrees. After stimulating with gardiquimod, the expression
of the IL-15V1, 3 increased about 4.5 times on RNA level, the other expression
was only up-regulated about 2 times. We also discovered that gardiquimod could
activate the MAPK/ERK- and PI3K/AKT-signaling pathways, and the specific
inhibitors studies indicate that, the effect of gardiquimod on these genes
expression is mainly or partially dependent on the activation of these two
signaling pathways. To sum up, the activation of TLR7 signaling pathway may
modulate some genes expression in Hela cells and may contribute to the
pathogenesis of the cervical cancer.
PMID- 24347178
TI - The C-terminal cytoplasmic portion of the NhaP2 cation-proton antiporter from
Vibrio cholerae affects its activity and substrate affinity.
AB - In this work, we report the phenotypic and biochemical effects of deleting the C
terminal cytoplasmic portion of the NhaP2 cation/proton antiporter from Vibrio
cholerae. While the deletion changed neither the expression nor targeting of the
Vc-NhaP2 in an antiporter-less Escherichia coli strain, it resulted in a changed
sensitivity of the host to sodium ions at neutral pH, indicating an altered Na(+)
transport through the truncated variant. When assayed in inside-out sub-bacterial
vesicles, the truncation was found to result in greatly reduced K(+)/H(+) and
Na(+)/H(+) antiport activity at all pH values tested and a greater than fivefold
decrease in the affinity for K(+) (measured as the apparent K m) at pH 7.5. Being
expressed in trans in a strain of V. cholerae bearing a chromosomal nhaP2
deletion, the truncated nhaP2 gene was able to complement its inability to grow
in potassium-rich medium at pH 6.0. Thus the residual K(+)/H(+) antiport activity
associated with the truncated Vc-NhaP2 was still sufficient to protect cells from
an over-accumulation of K(+) ions in the cytoplasm. The presented data suggest
that while the cytoplasmic portion of Vc-NhaP2 is not involved in ion
translocation directly, it is necessary for optimal activity and substrate
binding of the Vc-NhaP2 antiporter.
PMID- 24347179
TI - pT4 stage II and III colon cancers carry the worst prognosis in a nationwide
survival analysis. Shepherd's local peritoneal involvement revisited.
AB - The aim of this study is to clarify the prognostic importance of several well
known but still debated pathological variables related to the survival of colon
cancer patients. The study focuses on the definition and survival carried by the
pT4 category and stage II where the presence of high-risk variables may determine
whether or not adjuvant chemotherapy is administered. A retrospective nationwide
study was carried out including all colon cancer patients that underwent
resection in Iceland between 1990 and 2004 (n = 889). All histopathology was
reassessed. Cancer-specific survival (CSS) and overall survival were analysed
using Kaplan-Meier and Cox regression analysis. In stage II, the five-year CSS
for pT4 was 50% (95% CI, 32-69%), which was the lowest survival observed in that
stage. In stage III the five-year CSS was 30% (95% CI, 18-41%) and 37% (95% CI,
26-48%) for pT4 and pN2 tumors, respectively. Lymphatic invasion and
differentiation had no prognostic value in stage II. The survival associated with
pT4a versus pT4b depends on how these categories are defined with regard to
Shepherd's local peritoneal involvement (LPI). In the present series, pT4 is a
major indicator of poor prognosis in patients with stage II and III colon
carcinoma. Four-tiered TNM or Dukes staging systems are insufficient by not
taking this variable into account. Only Shepherd's LPI4 and a subgroup of LPI3
(i.e., borderline LPI3/LPI4) should qualify for the pT4a subcategory. The results
do not support lymphatic invasion or poor differentiation as high-risk stage II
variables.
PMID- 24347180
TI - Increased risk of dementia in patients with osteoporosis: a population-based
retrospective cohort analysis.
AB - Osteoporosis is a common systemic skeletal disease that predominantly affects
people older than 50 years and often co-occurs with dementia. The purpose of this
study was to evaluate the risk of dementia in osteoporosis patients in Taiwan.
Using data from Taiwan's National Health Insurance Research Database (NHIRD), we
identified 23,941 patients with osteoporosis from 2000 to 2010 and 47,579
nonosteoporosis control patients, frequency-matched for age, sex, and index year,
excluding patients with dementia at the baseline. We conducted univariate and
multiple Cox proportional-hazards regression analyses to calculate the hazard
ratios (HRs) and 95 % confidence intervals (CIs) of the association between
osteoporosis and risk of dementia. After adjustment for potential risk factors,
the osteoporosis patients exhibited 1.46-fold and 1.39-fold higher risk of
dementia (95 % CI = 1.37-1.56) and Alzheimer's disease (95 % CI = 0.95-2.02),
respectively, compared with the matched nonosteoporosis patients. We observed
increased risk of dementia in both men and women with osteoporosis. The
osteoporosis patients receiving bisphosphonate treatment or estrogen
supplementation were associated with significantly lower risk of dementia
compared with the osteoporosis patients who did not receive any treatment.
Overall, our results suggest higher risks of dementia in osteoporosis patients
than in nonosteoporosis patients. Osteoporosis could thus be considered an early
risk factor for dementia. Future large-scale double-blind randomized clinical
trials are required to clarify the role of medication in osteoporosis-related
dementia.
PMID- 24347181
TI - Genome-wide analysis of DNA methylation in an APP/PS1 mouse model of Alzheimer's
disease.
AB - To investigate aberrant genome-wide CpG methylation patterns in cortex brain
tissue of APP/PS1 mice and as compared to controls, which allows for
identification of novel disease-associated genes. This study investigates the
genome-wide DNA methylation profiles of the cortex from APP/PS1 transgenic mice
and control mice using the Roche NimbleGen chip platform. Functional analysis was
then conducted by Ingenuity Pathways Analysis system. The methylated DNA
fragments in the genome of each sample were enriched by MeDIP and the whole
genome interrogations were hybridized to the Roche NimbleGen Human DNA
Methylation 3x720 K CpG Island Plus RefSeq Promoter Array that cover 15,980 CpG
islands and 20,404 reference gene promoter regions of the entire human genome.
Analysis reveals 2346 CpG sites representing 485 unique genes as potentially
associated with AD disease status pending confirmation in additional study. At
the same time, these hyper-methylated genes display familial aggregation. An
impairment of the transforming growth factor-beta1 (TGF-beta1) signaling pathway
has been demonstrated to be specific to the AD brain and, particularly, to the
early phase of the disease, supporting a role for epigenetic change of TGF-beta1
in AD pathology. In future research, we will focus on TGF-beta1, as it appeared
to be the most promising candidate for AD.
PMID- 24347182
TI - How to treat tumefactive demyelinating disease?
AB - Glioma-like inflammatory demyelinating lesions can be found in patients with pre
diagnosed multiple sclerosis, but they have also been described as an isolated
disease entity. The initial diagnostic work-up usually includes a biopsy for
histopathological analysis. However, even after unambiguous histopathologic
classification, tumefactive lesions pose a therapeutic challenge. Until now,
there have been no guidelines on how to treat patients with these rare and
extreme lesion phenotypes. Here we report a patient with a relapsing unifocal
tumefactive demyelinating lesion. The patient initially showed a good response to
steroid treatment, with full clinical recovery. However, after relapse of the
same lesion, recovery was incomplete. Although immunosuppression was initiated,
the patient presented with subsequent further deterioration. Only maximal
escalation of immunosuppression was able to stop the inflammatory activity. Due
to the length of time of the step-wise escalation treatment however, the lengthy
lesion activity led to irreversible tissue destruction and residual non-remitting
disability. Early aggressive treatment with an induction therapy regimen might be
more appropriate for these rare and often strongly disabling lesion subtypes.
PMID- 24347183
TI - Does multiple sclerosis affect glucose tolerance?
AB - Based on current literature, it is not clear if multiple sclerosis (MS) patients
are at increased risk to develop impaired glucose tolerance (IGT). Eighty-one MS
patients and 45 healthy controls (HC) performed an oral glucose tolerance test.
IGT was defined as a fasting glucose concentration of 6.1-6.9 mmol/l and two-hour
post-load glucose of 7.8-11.1 mmol/l. The prevalence of impaired fasting glucose
concentrations (17% vs 2%) and IGT (11% vs 0%) was higher in MS patients than HC.
Accordingly, the areas under the glucose and insulin curves were higher in MS
patients. The current study demonstrates an elevated IGT-prevalence in MS.
PMID- 24347184
TI - Changes in functional network centrality underlie cognitive dysfunction and
physical disability in multiple sclerosis.
AB - BACKGROUND: Cognitive dysfunction in multiple sclerosis (MS) has a large impact
on the quality of life and is poorly understood. OBJECTIVE: The aim of this study
was to investigate functional network integrity in MS, and relate this to
cognitive dysfunction and physical disability. METHODS: Resting state fMRI scans
were included of 128 MS patients and 50 controls. Eigenvector centrality mapping
(ECM) was applied, a graph analysis technique that ranks the importance of brain
regions based on their connectivity patterns. Significant ECM changes were
related to physical disability and cognitive dysfunction. RESULTS: In MS
patients, ECM values were increased in bilateral thalamus and posterior cingulate
(PCC) areas, and decreased in sensorimotor and ventral stream areas. Sensorimotor
ECM decreases were related to higher EDSS (rho = -0.24, p = 0.007), while ventral
stream decreases were related to poorer average cognition (rho = 0.23, p =
0.009). The thalamus displayed increased connectivity to sensorimotor and ventral
stream areas. CONCLUSION: In MS, areas in the ventral stream and sensorimotor
cortex appear to become less central in the entire functional network of the
brain, which is associated with clinico-cognitive dysfunction. The thalamus,
however, displays increased connectivity with these areas. These findings may aid
in further elucidating the function of functional reorganization processes in MS.
PMID- 24347185
TI - Building highly functional interprofessional teams in our practices.
PMID- 24347186
TI - Measuring team development in clinical care settings.
AB - BACKGROUND AND OBJECTIVES: Our objective was to describe the psychometric
properties of a measure of team development that can be used to assess and guide
team functioning in health care settings. METHODS: The Team Development Measure
(TDM) is a 31-item questionnaire constructed using the Rasch rating scale
measurement model. We conducted an Mplus exploratory factor analysis using data
collected from 1,194 individuals representing 120 different teams. Team size
ranged from three to 39 members from rural and urban inpatient and ambulatory
health care settings. Here we characterize the domains of teamness, while taking
into account the development of teams over time. RESULTS: The TDM was found to
have good psychometric properties with little measurement error and a Rasch
person reliability of 0.95. Overall Cronbach's alpha was 0.97. An Mplus
exploratory factor analysis combined with the stochastic nature of the Rasch
model suggests a developmental sequence in building teams consisting of four sub
domains with the following mean item difficulty scores: cohesion=40.5, standard
deviation (SD)=2.68, communication=49.3 (SD=2.78), roles and goals=52.7
(SD=2.74), and team primacy=53.3 (SD=1.06). This pattern suggests cohesiveness is
an initial element for team development, followed by communication, roles and
goals clarity, and team primacy. CONCLUSIONS: We developed and tested a measure
of team development that has strong psychometric properties. This tool could be
used to study how team functioning affects clinical outcomes and as a quality
improvement tool to improve team function.
PMID- 24347187
TI - Satisfaction, early removal, and side effects associated with long-acting
reversible contraception.
AB - BACKGROUND AND OBJECTIVES: Although intrauterine devices (IUDs) and subdermal
implants (SDI) are recommended as first-line contraception for the majority of
women by the American College of Obstetrics and Gynecology, these methods of long
acting reversible contraception (LARC) are underutilized. Some concerns regarding
their use include cost of placement, side effects, and perception of frequent
early removal. This study evaluated satisfaction with LARC, frequency, and
reasons behind early removal in a family medicine setting. METHODS: Women > 18
years seen for placement of removal of an IUD or SDI were identified from billing
data and surveyed via telephone to determine satisfaction and side effects with
LARC. Additional demographic information was extracted from the electronic health
record. RESULTS: Of the 132 respondents (response rate 61.4%), 58.3% had IUDs and
41.7% had SDIs placed. Early removal occurred in 24.2% of women, and 72.7% were
satisfied with their contraceptive choice. Younger and nulliparous women were
more likely to have an SDI placed, whereas older and multiparous women chose the
IUD. Younger nulliparous women were less likely to have LARC removed early. Pain
(more commonly reported with the IUD) and increased frequency in bleeding (more
commonly reported with the SDI) were associated with early removal rates.
CONCLUSIONS: Most women who received LARC were satisfied with their contraceptive
choice, and only one in four had the LARC removed early. This is significantly
better than continuation rates with other contraceptive methods. Younger,
nulliparous women were good candidates for LARC, continuing their use more than
older, multiparous women. Improved counseling regarding pain and changes in
menstrual bleeding patterns may impact early removal of IUDs and SDIs,
respectively.
PMID- 24347188
TI - Measuring family physician identity: the development of a new instrument.
AB - OBJECTIVE: Our objective was to describe the development and psychometric
assessment of an instrument designed to assess family medicine identity in
residency training sites and compare responses from physician faculty and
residents. METHODS: We conducted 28 focus groups between 2007--2008, 14 with
faculty and 14 with residents who were part of the Preparing Personal Physicians
for Practice (P4) Project. The first 22 focus groups were exploratory, and the
second six were confirmatory where we shared working variable statements scored
using a 5-point Likert scale. We then administered the survey to 223 faculty and
147 residents who were part of the P4 Project, followed by a principal component
(factor) analysis, retaining items that reflected domains with eigenvalues higher
than 1.0. RESULTS: A total of 223 family physician faculty and 147 residents
completed the identity survey. The item analysis extraction loadings ranged from
0.36 to 0.70. Based on item grouping patterns, five domains were reflected in the
data: Patient/Family Relationships, Patient Advocacy, Career Flexibility,
Balancing the Breadth and Depth in Practice, and Comprehensive Nature of Patient
Care. Compared to residents, faculty conveyed stronger agreement about being
comfortable balancing the breadth and depth of medical knowledge needed in
practice and using a variety of approaches to supplement their medical knowledge
about patient care compared to residents (90.6% versus 68.7% for breadth and
depth, 95.9% versus 88.3 for using a variety of approaches). Compared to faculty,
residents agreed more strongly that the ability to choose many options in how to
build their practice appeals to them compared to faculty (89.1% versus 82.9%).
CONCLUSIONS: We successfully developed and tested a survey designed to measure
family medicine identity in residencies, with five domains. Survey item responses
were different between residents and faculty, which indicates the instrument may
be sensitive to important changes over time.
PMID- 24347189
TI - Advancing geriatrics fellowship programs through a community-based residency
network.
AB - BACKGROUND AND OBJECTIVES: Our nation faces unprecedented challenges in caring
for older adults. Geriatricians who provide care and teach geriatrics are
underrepresented in the workforce, especially in non-metropolitan communities. In
Michigan, geriatricians and geriatrics fellowship (GF) programs are clustered in
the Southeast, suggesting that training site demographics may influence fellows'
career location decisions. A project was undertaken at Michigan State University
to determine if an established family medicine residency network (FMRN) could
facilitate the accreditation of new GF programs in non-metropolitan communities,
recruit fellows, and retain graduates to practice and teach in neighboring areas.
METHODS: A team (department chair, appointed GF network director, site program
directors, and education specialists) conducted participating site needs and
readiness assessments, facilitated collaboration between GF programs, assisted
with completion of new program applications, led development of a curriculum
utilizing shared instructional resources and evaluation tools, and provided
career counseling to fellows. RESULTS: Two GF programs were accredited and
accepted applicants. Ongoing cooperative efforts resulted in the writing of a GF
curriculum, organization of a joint Observed Structured Clinical Evaluation
(OSCE), and monthly information-sharing teleconferences with program directors.
Following training, graduates have chosen to practice in areas underserved by
geriatricians in Michigan and elsewhere. CONCLUSIONS: Early experience with this
model of GF development indicates that new fellowships can be established in
community-based residencies that competitively recruit and train fellows who are
inclined to practice in areas of greatest need. Creation of more non-metropolitan
GF programs could provide a means to stabilize and redistribute the geriatrician
workforce.
PMID- 24347190
TI - Resident time in continuity practice.
AB - BACKGROUND AND OBJECTIVES: Family medicine residents are required to maintain a
continuity practice in an approved family medicine center (FMC) and achieve
minimum targets for patient encounters. In the past, minimum periods of time in
the FMC were defined in the program requirements, but these have now been
replaced with target numbers of patient encounters. As residency programs come
under increasing pressure to address service needs on patient care services, some
program directors face requests by hospital administration to benchmark their
requirements for resident schedules in the FMC against national standards. Since
no such standards presently exist, the authors decided to determine the average
frequency with which residents are currently scheduled in their FMC continuity
practices in order to meet accreditation requirements. METHODS: Using the data
set from the 2011 American Academy of Family Physicians (AAFP) annual residency
census and residency directory questionnaire, the frequency of reported resident
scheduling in the FMC continuity practice was extracted. Although the census
itself achieves a 100% response rate, not all programs respond to all of the
residency directory questions. In this case, for reported time in the FMC, an 84%
(380 out of 450 programs) response rate was achieved. RESULTS: Family medicine
residency programs currently schedule residents in their FMC continuity practice
substantially more often than previously required. CONCLUSIONS: To meet current
accreditation requirements, family medicine residency programs schedule residents
in their FMC continuity practices more than previously required minimums.
PMID- 24347192
TI - Come July.
PMID- 24347191
TI - Responding to a changing nation: are faculty prepared for cross-cultural
conversations and care?
AB - BACKGROUND AND OBJECTIVES: The United States is becoming increasingly diverse.
Health disparities continue with little improvement despite national policies and
standards. Medical institutions are modifying their curricula; however, little is
known about faculty attitudes and comfort in addressing cultural issues. The
purpose of this study was to determine faculty attitudes, self-perceived levels
of comfort and skill, and future knowledge needs pertaining to cultural
competence. METHODS: A survey was administered to all clinical faculty at the
University of Virginia School of Medicine. Survey questions addressed faculty
attitudes and self-perceived levels of comfort and skill in dealing with cultural
issues, as well as perceived need and interest in future cultural competence
training. RESULTS: When considering each phase of education (medical school,
residency, continuing medical education [CME]), fewer than 25% of the respondents
reported receiving formal instruction in cultural competency in any given phase,
although 93% felt that cultural competency training was important. Fifty-eight
percent felt "very comfortable" caring for diverse patients, although this
dropped to 30% when specifying limited English proficiency. The situation in
which the highest percentage of respondents felt "not particularly comfortable"
or "not at all comfortable" was breaking bad news to a patient's family first if
this was more culturally appropriate (47%). Respondents felt most skilled in
working with medical interpreters, apologizing for cross-cultural
misunderstandings, and eliciting the patients' perspectives about their health
and illness. Respondents felt the least skilled providing culturally sensitive
end-of-life care and dealing with cross-cultural conflicts. CONCLUSIONS: Clinical
faculty have received limited instruction on cultural competency, and the
reported levels of comfort and skill in many challenging areas of multicultural
health leave much room for improvement. Until faculty become more comfortable and
are able to model and teach these behaviors to learners, positive responses to
national policies in culturally competent care are likely to be limited.
PMID- 24347193
TI - Combat mentoring.
PMID- 24347194
TI - Building relationships-one patient at a time.
PMID- 24347196
TI - Meta-analysis.
PMID- 24347197
TI - Interdisciplinary family medicine.
PMID- 24347198
TI - Current evidence for ART practice: the Cochrane of Cochranes on optimising
outcomes.
PMID- 24347199
TI - Advanced wound care therapies in non-healing lower extremity ulcers: high
expectations, low evidence.
PMID- 24347200
TI - Maternal obesity during pregnancy is associated with adult offspring
cardiovascular morbidity and mortality but may represent confounding by other
factors.
PMID- 24347201
TI - History and physical examination provide little guidance on diagnosis of rotator
cuff tears.
PMID- 24347203
TI - Case Study Interpretation - Fort Lauderdale Case 2.
PMID- 24347202
TI - P-113 peptide: New experimental evidences on its biological activity and
conformational insights from molecular dynamics simulations.
AB - In this article, we report novel and additional results, both experimental and
computational, obtained in our laboratories on the peptide P-113. In particular,
our experimental results indicate that this peptide is endowed with a high target
cell selectivity towards yeast species, suggesting its potential development as a
new drug against oral microbial infections. To provide additional structural
insights, we performed several Molecular Dynamics simulations in different
conditions. Results suggest that P-113 is a rather compact species presumably
because of its highly charged state as emerged from the dramatic increase of
internal fluctuation occurring upon point-mutation. The peptide turns out to
adopt, in water, a beta-hairpin-like conformation and, in a more hydrophobic
environment, is found to be in a (probably slow) equilibrium between alpha-helix
and hairpin conformations. Complexation with Zn(2+) induces a drastic mechanical
stabilization, which prevents any conformational organization of the peptide into
a biologically active state.
PMID- 24347204
TI - Detection of candidate tumor driver genes using a fully integrated Bayesian
approach.
AB - DNA copy number alterations (CNAs), including amplifications and deletions, can
result in significant changes in gene expression and are closely related to the
development and progression of many diseases, especially cancer. For example, CNA
associated expression changes in certain genes (called candidate tumor driver
genes) can alter the expression levels of many downstream genes through
transcription regulation and cause cancer. Identification of such candidate tumor
driver genes leads to discovery of novel therapeutic targets for personalized
treatment of cancers. Several approaches have been developed for this purpose by
using both copy number and gene expression data. In this study, we propose a
Bayesian approach to identify candidate tumor driver genes, in which the copy
number and gene expression data are modeled together, and the dependency between
the two data types is modeled through conditional probabilities. The proposed
joint modeling approach can identify CNA and differentially expressed genes
simultaneously, leading to improved detection of candidate tumor driver genes and
comprehensive understanding of underlying biological processes. We evaluated the
proposed method in simulation studies, and then applied to a head and neck
squamous cell carcinoma data set. Both simulation studies and data application
show that the joint modeling approach can significantly improve the performance
in identifying candidate tumor driver genes, when compared with other existing
approaches.
PMID- 24347205
TI - New Italian guidelines for malaria prophylaxis in travellers to endemic areas.
AB - BACKGROUND AND METHODS: As a consequence of the rapid evolution of malaria
prophylaxis recommendations throughout the world, the Italian Society of Tropical
Medicine (SIMET-Societa Italiana di Medicina Tropicale) has set up a working
group in charge of preparing a new national guideline. Other scientific societies
interested in the topic were also involved in the project. RESULTS AND
CONCLUSIONS: The group stated that awareness about malaria risk and
characteristics, as well as protection from mosquito bites, are recommended for
all travellers visiting malaria-endemic countries. The risk and benefit of
malaria chemoprophylaxis must be carefully balanced before prescribing drugs: the
disease-related risk must outweigh the possibility of drugs' side effects. As a
general rule, malaria pills are the first choice for travellers to high-risk
areas, such as sub-Saharan Africa, Eastern India, Myanmar, Eastern Indonesia,
Papua New Guinea and, with some limitations, South-East Asia, and the Amazon part
of Venezuela, Guyana and French Guyana. However, several other factors, such as
itinerary, season, duration of trip, availability of insect bite protection, pre
existing conditions and compliance, must be taken into account. In low-risk
areas, stand-by emergency treatment is the first option. In minimal-risk areas
and in Plasmodium vivax areas, a prompt diagnosis only is advised (Central
America, South America outside the Amazon basin, Middle East, China, Thailand,
Nepal). Recommendations may be modified when particular groups of travellers are
concerned, such as long-term residents, visiting friends and relatives, patients
with pre-existing conditions, pregnant women and children.
PMID- 24347206
TI - Dynamic ultrasonic nebulisation extraction coupled with headspace ionic liquid
based single-drop microextraction for the analysis of the essential oil in
Forsythia suspensa.
AB - INTRODUCTION: Ionic liquids have attracted much attention as an extraction
solvent instead of traditional organic solvent in single-drop microextraction.
However, non-volatile ionic liquids are difficult to couple with gas
chromatography. Thus, the following injection system for the determination of
organic compounds is described. OBJECTIVE: To establish an environmentally
friendly, simple, and effective extraction method for preparation and analysis of
the essential oil from aromatic plants. METHODS: The dynamic ultrasonic
nebulisation extraction was coupled with headspace ionic liquid-based single-drop
microextraction(UNE-HS/IL/SDME)for the extraction of essential oils from
Forsythia suspense fruits. After 13 min of extraction for 50 mg sample, the
extracts in ionic liquid were evaporated rapidly in the gas chromatography
injector through a thermal desorption unit (5 s). The traditional extraction
method was carried out for comparative study. RESULTS: The optimum conditions
were: 3 MUL of 1-methyl-3-octylimidazolium hexafluorophosphate was selected as
the extraction solvent, the sample amount was 50 mg, the flow rate of purging gas
was 200 mL/min, the extraction time was 13 min, the injection volume was 2 MUL,
and the thermal desorption temperature and time were 240 degrees C and 5 s
respectively. Comparing with hydrodistillation (HD), the proposed method was
environment friendly and efficient. CONCLUSION: The proposed method is
environmentally friendly, time saving, with high efficiency and low consumption.
It would extend the application range of the HS/SDME and would be useful
especially for aromatic plants analysis.
PMID- 24347207
TI - The role of thoracic trauma in inflammatory responses, apoptosis and bacterial
translocation following multiple traumas.
AB - BACKGROUND: Blunt chest trauma and its complications are commonly encountered in
emergency medicine. Herein, we used a rat model to investigate the role of
thoracic trauma in inflammation, apoptosis and bacterial translocation following
multiple traumas. METHODS: Ninety Wistar rats were divided equally into nine
groups. Rats underwent a standardized blunt thoracic and/or head trauma and were
sacrificed 24 or 48 hours after the trauma. Specimens from various organs and
blood samples were collected and quantitatively cultured for aerobic organisms.
Interleukins, TNF-alpha, and MCP-1 levels were assessed in the sera and markers
of apoptosis were detected in the lungs. RESULTS: Levels of interleukins, TNF
alpha and MCP-1 in all of the groups undergoing trauma were significantly higher
than those of the control group (p=0.001). Levels of apoptotic cells in the
groups undergoing head and thoracic trauma (HTT) were significantly higher than
those of the control group (p=0.009). Light microscopic evaluation indicated that
damage in the HTT groups was significantly higher than that in the control group.
The incidence of bacterial translocation was also significantly higher in the HTT
groups (p=0.003). CONCLUSION: Multiple inflammatory mediators are activated in
multiple traumas (including blunt thoracic trauma), which allow bacterial
translocation and apoptotic processes to occur. Our results indicate that
thoracic trauma plays a major role in post-traumatic bacterial translocation,
inflammation, and apoptosis following multiple traumas.
PMID- 24347208
TI - Hypertonic saline, normal saline or neither: which is best for uncontrolled
hemorrhagic shock? An experimental study in goats.
AB - BACKGROUND: To evaluate the effects of various fluids on uncontrolled hemorrhagic
shock (UHS). Controversy exists over the appropriate doses and types of fluids
for best treating UHS. This study evaluated the effects of hypertonic saline
(HTS), normal saline (NS), and no fluid resuscitation (NFR) on UHS. METHODS:
Thirty goats were anesthetized and underwent right leg ablation. The animals were
randomly assigned to equal NFR, HTS, and NS groups. The following features of UHS
were analyzed: hemoglobin, heart rate, blood loss, mean arterial pressure,
bleeding time, and pH. Animals were sacrificed two hours after ablation. RESULTS:
All of the goats who received HTS died within 60 minutes. Four goats in the NS
group and one goat in the NFR group died within 120 minutes. The NFR group had
significantly higher hemoglobin values than the NS and HTS groups at the end of
the trial. Blood loss in the HTS group was greater than in the other two groups
(p<0.05). The NS group had higher blood loss than the NFR group (p<0.05). Mean
arterial pressure in the HTS group decreased sharply toward zero within the first
60 minutes. In the NFR and NS groups, mean arterial pressure was higher than in
the HTS group (p<0.05), and remained constant at 60mmHg after 35 minutes. The NFR
group had higher pH values compared to the other two groups (p<0.05). CONCLUSION:
Our study demonstrated that HTS is not suitable for treating UHS when compared to
NFR and NS. Goats treated with NFR had superior values for all UHS features,
including hemoglobin, pH, blood pressure, and bleeding time, compared to those
treated with HTS and NS. Pre-hospital field treatment with NS or HTS may worsen
the condition until surgical repair is accomplished.
PMID- 24347209
TI - Antioxidant and anti-inflammatory effects of curcumin against hepatorenal
oxidative injury in an experimental sepsis model in rats.
AB - BACKGROUND: To investigate the effects of curcumin, an antioxidant and anti
inflammatory agent, on free oxygen radicals and lipid peroxidation in an
experimental sepsis model, as well as to determine the role of curcumin in
preventing hepatorenal tissue damage caused by sepsis. METHODS: The rats were
randomly divided into three groups (n=8) as follows: control group (group 1);
sepsis group (group 2); and sepsis + curcumin group (group 3). Sepsis was created
using the cecal ligation and perforation (CLP) method. Curcumin was administered
intraperitoneally (200 mg/kg) in two equal doses just after the perforation and
at twelve hours post-perforation. RESULTS: Serum TNF-a and IL-1beta, and tissue
MDA and MPO values were higher, whereas tissue GSH and Na+/K+-ATPase values were
lower, in group 2 as compared to group 1. These values in group 3 were the
inverse of those in group 2. As compared to group 1, histopathological evaluation
of group 2 showed damaged hepatocytes, glomeruli, and tubules, whereas the damage
was significantly reduced in group 3 as compared to group 2. CONCLUSION: The
strong antioxidant and anti-inflammatory effects of curcumin against potential
hepatorenal damage were shown using an experimental sepsis model in rats.
PMID- 24347210
TI - Management of soft tissue extremity degloving injuries with full-thickness grafts
obtained from the avulsed flap.
AB - BACKGROUND: A "degloving injury" is referred to as seperation of cutaneous tissue
from the deeper structures of the body. Although many methods have been defined
to reform the tissue integrity; defatting and readaptation of the avulsed flap
still comprises one of the most effective methods. METHODS: From 2000-2012, we
treated a total of nine patients with avulsed extremities with defatting and
readaptation of the same flap. The fat compartment of the flaps was removed and
the skin was meshed. The patients were followed-up with for an average of 12
months (range: 8-18 months). RESULTS: Total closure of the defect and healing was
achieved in seven patients. Although 30% of the total surface area of the graft
was lost in one patient, and 10% in another, total epithelialization was achieved
later with secondary grafting. CONCLUSION: Defatting, meshing and readaptation of
the same flap to its original site is still a valuable option for avulsion
injuries because of the relative ease of the procedure, shorter operative times,
and usability of the procedure by general surgeons. This technique might be
particularly important in places where a reconstructive plastic surgeon is not
available.
PMID- 24347211
TI - Functional outcomes after treatment of traumatic brachial plexus injuries:
clinical study.
AB - BACKGROUND: The aim of this study is to evaluate functional outcome and quality
of life using statistically validated tools. METHODS: Participating patients were
called and asked questions from the Short Form 36 (SF-36), the Disability of the
Arm, Shoulder and Hand (DASH) questionnaire, a pain scale and an additional
question on their satisfaction with surgery. RESULTS: A total of 33 patients were
operated by a single surgeon (MI) between 1997 and 2010 at the Neurosurgery
Department of Istanbul School of Medicine. Three of these patients refused to
participate and three other patients were excluded, leaving 27 patients, with an
average follow-up of 79,6 months, for review. The most common cause of traumatic
brachial plexus injuries (TBPI) was motor vehicle accidents. Fourteen patients
had isolated supraclavicular injuries and three patients had infraclavicular
injuries. The remaining 10 patients' injuries were both supra- and
infraclavicular. Avulsion was encountered in three patients. The patients who
were operated within the first six months after trauma represented significantly
better scores in DASH, SF-36 and pain scale. CONCLUSION: Statistically validated
tests like DASH and SF-36 questionnaires are valuable tools for evaluating TBPI
patients. Centers specialized in treating TBPI with surgery may use these tests
pre- and postoperatively which lead to objective personalized evaluation of
patients' subjective symptoms.
PMID- 24347212
TI - Factors affecting mortality caused by falls from height.
AB - BACKGROUND: Falls from height are among the most common trauma cases presenting
to emergency departments and often cause mortality and morbidity. In the present
study, we aimed to determine the factors that effectively reduce mortality caused
by falls from height. METHODS: Data from 2252 trauma patients who presented to
Dicle University Emergency Service between January 2005 and December 2008 due to
falling from height in the Southeastern Anatolia region were retrospectively
analyzed. We analyzed the parameters that are considered to have a positive
effect on mortality, which included the following: month of fall; age; gender;
etiology; place of fall; type of ground on which the patient fell; height of
fall; intubation; hypotension; tachycardia; neck, head, thoracal, abdominal,
pelvic, and extremity injuries; Glasgow Coma Score (GCS); Injury Severity Score
(ISS); and Revised Trauma Score (RTS). RESULTS: There were 1435 males (63.7%) and
817 females (36.3%) included in the study. Two thousand thirty-one (94.6%)
patients survived the fall while 121(5.4%) died. The mean age of the surviving
patients was 15.55+/-18.60 years, while the patients who died had a mean age of
29.59+/-28.93 years. The mean height of the fall of the survivors' was 3.09
meters, and the mean height of the fall for those that died was 6.61+/-5.73
meters (p<0.001). CONCLUSION: The mean fatal height of the fall in falls from
height is 6.61 m. Age, attempted suicide, height of fall, type of ground on which
the patient fell, place of fall, and head, thoracic, and abdominal trauma are the
primary factors affecting mortality caused by falls from height.
PMID- 24347213
TI - An analysis of firearms-related deaths between 1993-2010: a retrospective study.
AB - BACKGROUND: Firearm injuries (FI) are the most common cause of death among
military personnel. In this study, postmortem examination and autopsy records of
deaths resulting from firearm injuries recorded in the Department of Forensic
Medicine of Gulhane Military Medical Academy between 1993-2010 were examined
retrospectively. METHODS: We evaluated the characteristics of 153 firearm deaths
accounting for 36.6% of all medical-legal autopsies. The cases included 152 men
(99.3%) and 1 woman (0.7%). RESULTS: The mean age of the cases was 23.1 years (+/
4.7; range, 20-43 years). The manner of death was determined in all cases with
41.8% of cases identified as suicide and 39.9% as homicide. The most common sites
of firearm entrance wounds were the head and neck region (n=109, 71.2%), the
chest (n=26, 17%), or the abdomen (n=14, 9.2%). The type of firearm was not clear
in most cases. CONCLUSION: In conclusion, complete forensic and medical records
will facilitate the rapid and accurate conclusion of the legal process and will
enhance future retrospective studies.
PMID- 24347214
TI - A new application technique of circular fixator for the treatment of open tibial
fractures: circular fixator-hinge technique.
AB - BACKGROUND: The purpose of this study is to present and validate a hinge-fixator
technique for the treatment of open tibial fractures, which has advantages in
application and the follow up period. METHODS: The technique was used in open
tibia fractures of 14 adult patients. Using this method, initial anatomic
reduction was achieved and temporary stability was obtained on the hinge-fixator
after applications were completed. Patients' radiological and clinical results
were analyzed using the Paley's criteria at the time of the last follow-up.
RESULTS: Patients were brought in for followed up analysis over a 5.4 year
period. According to Paley, two patients had 'good' and 12 patients had
'excellent' radiological results, while the functional result were excellent
(n=13) and good (n=1), respectively. CONCLUSION: The hinge-fixator technique is a
fast and easy method that contributes to shorter operation times, reduced
radiation exposure, and more comfortable treatment periods.
PMID- 24347215
TI - Cemented calcar replacement versus cementless hemiarthroplasty for unstable
intertrochanteric femur fractures in the elderly.
AB - BACKGROUND: Unstable intertrochanteric fractures remain a challenging problem in
elderly individuals due to high failure rates associated with internal fixation.
Hemiarthroplasty is one treatment option for intertrochanteric femur fractures in
elderly patients. The aim of the present study was to compare the reliability of
cementless and cemented hemiarthroplasty for unstable intertrochanteric femur
fractures in elderly patients. METHODS: Elderly patients with AO type 31-A2
intertrochanteric femur fractures were treated with cemented (n=40) or cementless
(n=46) hemiarthroplasty. Duration of surgery, amount of blood loss and blood
transfusion, Harris hip scores, rate of loosening of the femoral component,
duration of hospital stay after surgery and mortality rates were recorded.
RESULTS: There were no significant differences between the groups in length of
hospital stays, Harris hip scores, amount of blood transfusions, implant
loosening and follow-up mortality rates. Walking ability was better in the
cemented group in the early follow-up period. Duration of surgery, amount of
blood loss and perioperative mortality rates were significantly lower in the
cementless group than in the cemented group. CONCLUSION: Cementless
hemiarthroplasty is a reliable treatment choice for unstable intertrochanteric
femur fractures in elderly patients with early mobilization, acceptable
functional results, low implant loosening rates, shorter surgery time, lesser
blood loss and lower perioperative mortality rate.
PMID- 24347216
TI - [Analysis of risk factors for the development of pediatric appendicitis].
AB - BACKGROUND: Appendicitis is the most common form of abdominal pain requiring
surgery among children. This study evaluates the association of age, sex,
seasonal, and familial factors with the histopathology of appendectomies.
METHODS: 588 patients who underwent operations for acute appendicitis between
2009 and 2011 were included in this study. The patients were classified in one of
three groups based on histopathological results: acute, perforated, and negative
appendectomy. This study evaluates the association between age, sex, seasonal,
and familial factors and the histopathological classification. RESULTS: The mean
age of the patients was 11.8+/-3.26 years (range 1 to 16 years). Among these
patients, appendicitis was 2.41 times more common in children greater than 10
years old. Appendicitis occurred 4.63 times more often among males than in
females. Negative appendectomy occurred more often in children greater than 10
years of age. Appendicitis was associated with both seasonal factors and family
history; however this association did not meet the threshold for statistical
significance (p>0.05). DISCUSSION: The age and sex of the patient should be taken
into account when considering appendicitis surgery to improve the accuracy of the
diagnosis. In addition, the histopathology of appendicitis is influenced by
familial and environmental factors.
PMID- 24347217
TI - [Can increased intra-abdominal pressure (IAP) be treated more effectively with
intravesical pressure measurement in high-risk patients?].
AB - BACKGROUND: Increased intra-abdominal pressure (IAP) can result in multiorgan
failure. Trauma, mechanical bowel obstruction (MBO), abdominal wall defects (AWD)
and fluid resuscitation in septic shock are conditions associated with a high
risk of increased IAP in children. It may be possible to treat these conditions
more effectively using intravesical pressure measurement. METHODS: This
prospective study was performed between December 2009 and October 2010.
Intravesical pressure (IVP) measurement was used to determine IAP. The presence
of Intra-abdominal hypertension (IAP >12 mmHg) and abdominal compartment syndrome
(IAP >15 mmHg + new organ dysfunction) was evaluated in all clinical decisions.
RESULTS: IVP monitoring was applied in all patients with abdominal trauma (14),
AWD (8), fluid resuscitation for septic shock (7), and MBO (6). A diagnosis of
ACS was determined in 14% of trauma patients and required surgery. IAH/ACS
occurred in 38% of AWD cases, which required closure. IAH occurred in 43% of
patients undergoing fluid resuscitation for septic shock, requiring decompressive
intervention. IAH/ACS occurred in 50 % of MBO patients, all of whom required
surgery. DISCUSSION: IVP measurement is a useful method to identify candidates
for surgical treatment in cases of trauma and MBO. Similarly, IVP monitoring can
facilitate the closure of abdominal wall defects and the application of fluid
resuscitation in septic shock.
PMID- 24347218
TI - Iliopsoas hematoma due to muscular rupture following defibrillation.
AB - We describe a 62 year old patient who presented with acute anterior ischemia and
subsequently developed an iliopsoas hematoma. The patient was treated surgically
due to rapid progression and femoral neuropathy, and the iliopsoas muscle rupture
was diagnosed intraoperatively. The rupture was related to the external
electrical defibrillation the patient had on admission. This was a rare case, and
we hope the report would help to raise physicians' awareness regarding this
complication and treatment.
PMID- 24347219
TI - Trauma-associated bleeding from the bilateral internal iliac arteries resolved
using angiographic embolization.
AB - Pelvic fracture is associated with high mortality. The management of major pelvic
injuries remains one of the most important issues in modern trauma care. A 39
year-old male patient presented at the emergency department after being hit with
a 500 kg load. His general condition was average with unstable vital signs.
Pelvic tomography revealed fractured bone structure, thickening secondary to
hematoma in both iliopsoas muscles, and hemorrhage-related active extravasation
in the left internal iliac trace. The patient's hemodynamics worsened despite
fluid and blood replacement, and angiographic embolization was scheduled.
Bilateral embolization of the iliac artery was performed. Control angiography
confirmed that full embolization was established. The patient was monitored in
intensive care, but expired after three days due to acute kidney failure,
disseminated intravascular coagulation, and multi-organ failure. Angiographic
embolization is a technique improves hemorrhage control in pelvic trauma but can
also increase risk of complications such as ischemia and necrosis.
PMID- 24347220
TI - A rare cause of acute appendicitis: an ingested foreign body.
AB - Various kinds of foreign bodies causing appendicitis have been reported. However,
a needle contained in the appendix is very rare, especially in adults. We report
an unusual case of a twenty year old man who had ingested a needle ten days prior
and presented with signs and symptoms of acute abdominal pain. An abdominal
computed tomography scan revealed acute appendicitis. The patient was
successfully treated with laparoscopic surgical intervention. In cases of a
foreign body in the gastrointestinal tract that cannot be removed endoscopically,
the emergence of non-specific symptoms may be early symptoms of acute problems in
the abdomen.
PMID- 24347221
TI - Acute intestinal obstruction secondary to left paraduodenal hernia: a case
report.
AB - Paraduodenal hernia, the most common type of internal herniation, is rare in the
etiology of intestinal obstruction. Delayed diagnosis and surgical intervention
may result in significant morbidity and mortality risk. This report presents a
case of left paraduodenal hernia resulting in acute intestinal obstruction. A 43
year old male patient was admitted with a diagnosis of acute intestinal
obstruction. A left paraduodenal hernia was identified by computed tomography
findings of an encapsulated cluster of dilated small bowel loops occupying the
left upper quadrant between the stomach and pancreas, and the presence of an
engorged and displaced vascular pedicle at the orifice of the hernia. Upon
further investigation, the dilated proximal jejunal segments were found in the
left paraduodenal fossa, enclosed in a hernia sac. After reducing the intestinal
segments to the abdominal cavity, the orifice of the hernia sac was closed by
suturing to the retroperitoneum. Paraduodenal hernia should be considered as a
possible etiology in cases of acute intestinal obstruction with unremarkable
presentations. Physicians should be familiar with the demonstrative imaging
findings of computed tomography of a paraduodenal hernia. Early surgical
intervention is critical to prevent the significant morbidity and mortality
associated with this condition.
PMID- 24347222
TI - [Late presentation of posttraumatic pulmonary arteriovenous fistulea occlusion
with septal occluder device].
AB - Posttraumatic pulmonary arteriovenous fistula is a rare complication of
penetrating injury. Cases may remain asymptomatic for years prior to diagnosis.
We present a case of pulmonary arteriovenous fistula related to a penetrating
injury of the thorax 6 years previously that was occluded with a septal occluder
device. Consistent use of CT or conventional catheter pulmonary angiography
following penetrating injury to the thorax is essential to the early diagnosis of
pulmonary arteriovenous fistula during the asymptomatic stage. Modern occlude
devices facilitate the transcatheter approach as a viable alternative to surgery
for the closure large, high pressure defects.
PMID- 24347223
TI - [Removal of mediastinal foreign body (steel shot) using mediastinoscopy: case
report].
AB - Morbidity and mortality is high in patients with gunshot wounds to the chest.
Only in rare cases do foreign bodies persist in the thorax without significant
pathology. At this study, we present a case in which steel shot was removed
through the mediastinum using mediastinoscopy due to the risk of tracheal
fistula.
PMID- 24347224
TI - FiO2 predicts outcome in infants with respiratory syncytial virus-induced acute
respiratory distress syndrome.
AB - OBJECTIVE: Respiratory syncytial virus (RSV) infection can progress to acute
respiratory distress syndrome (ARDS) in infants. ARDS is a life-threatening
condition that is characterized by severe hypoxemia, defined as PaO(2)/FiO(2)
ratio <300 mmHg. This ratio is used in many trials as the sole oxygenation
criterion for ARDS. Recently, however, it has been shown in adults with ARDS that
FiO(2), independently of the PaO(2)/FiO(2) ratio predicts mortality. Because
epidemiology and outcome of ARDS differ strongly between children and adults, we
determined if FiO(2) on admission (baseline FiO(2)) independently predicted the
duration of mechanical ventilation (MV) and length of stay (LOS) in the pediatric
intensive care unit (PICU) in infants with RSV-induced ARDS. DESIGN:
Retrospective observational study. SETTING: A 14-bed pediatric intensive care
unit. PATIENTS: One hundred twenty-nine mechanically ventilated infants with RSV
induced ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Independent
predictors for outcome, including baseline FiO(2) and PEEP, were analyzed using
the cox regression model. Endpoints were duration of MV and LOS in the PICU. A
higher baseline FiO(2) was independently associated with a longer duration of MV
(HR 0.12, CI 0.02-0.87, P = 0.036) and increased LOS in the PICU (HR 0.09, CI
0.01-0.57, P = 0.023). Neither baseline PEEP nor PaO(2)/FiO(2) ratio correlated
with outcome. CONCLUSIONS: FiO(2) level independently predicted outcome in
infants with RSV-induced ARDS, whereas both PEEP and the PaO(2)/FiO(2) ratio did
not. This suggests that FiO(2) should be taken into account in defining disease
severity in infants with RSV-induced ARDS.
PMID- 24347225
TI - Parallel processes: using motivational interviewing as an implementation coaching
strategy.
AB - In addition to its clinical efficacy as a communication style for strengthening
motivation and commitment to change, motivational interviewing (MI) has been
hypothesized to be a potential tool for facilitating evidence-based practice
adoption decisions. This paper reports on the rationale and content of MI-based
implementation coaching Webinars that, as part of a larger active dissemination
strategy, were found to be more effective than passive dissemination strategies
at promoting adoption decisions among behavioral health and health providers and
administrators. The Motivational Interviewing Treatment Integrity scale (MITI
3.1.1) was used to rate coaching Webinars from 17 community behavioral health
organizations and 17 community health centers. The MITI coding system was found
to be applicable to the coaching Webinars, and raters achieved high levels of
agreement on global and behavior count measurements of fidelity to MI. Results
revealed that implementation coaches maintained fidelity to the MI model,
exceeding competency benchmarks for almost all measures. Findings suggest that it
is feasible to implement MI as a coaching tool.
PMID- 24347226
TI - Expression of far upstream element (FUSE) binding protein 1 in human glioma is
correlated with c-Myc and cell proliferation.
AB - Glioma is one of the most common type of primary intracranial tumor. Although
great advances have been achieved in treatment of glioma, the underlying
molecular mechanisms remain largely unknown. Previous studies demonstrated that
FBP1 is a transcriptional regulator of c-Myc and acts as an important prognostic
indicator in many cancers. Our study aimed to assess the expression and function
of FBP1 in human glioma. Immunohistochemical and Western blot analysis were
performed in human glioma and normal brain tissues. High FBP1 expression (located
in cell nuclei) was observed in 70 samples and its level was correlated with the
grade of malignancy. A strongly positive correlation was observed between FBP1
and c-Myc (P = 0.005) and Ki-67 expression (P = 0.009). In a multivariate
analysis, high FBP1 and c-Myc expressions were showed to be associated with poor
prognosis in glioma. While in vitro, following serum stimulation of starved U87MG
cells, the expression of FBP1 was upregulated, as well as c-Myc and PCNA.
Moreover, knockdown of FBP1 by siRNA transfection diminished the expression of c
Myc and arrested cell growth at G1 phase. Collectively, our results shows that
the expression of FBP1 is in close correlation with c-Myc level and cell
proliferation in glioma and provides a potential strategy to develop FBP1
inhibitors as novel anti-tumor agents.
PMID- 24347227
TI - Stromal alterations as quantitative optical biomarkers of epithelial tumor
progression.
AB - Stroma plays an important role during epithelial tumor progression. Probing
stroma alteration may become an intrinsic indicator for evaluating epithelial
tumor progression. In this review, we summarize our recent works on stromal
alterations as quantitative optical biomarkers of epithelial tumor progression by
use of nonlinear optical microscopy.
PMID- 24347228
TI - Performance, egg quality traits, and serum metabolite concentrations of laying
hens affected by dietary supplemental chromium picolinate and vitamin C under a
heat-stress condition.
AB - A 3 * 2 factorial experiment consisting three levels (0, 200, and 400 MUg/kg) of
chromium (chromium picolinate) and two levels (0 and 250 mg/kg) of vitamin C was
employed to evaluate the effects of these dietary supplements on performance, egg
quality traits, and serum biochemical parameters of heat-stressed laying hens
(Lohmann LSL-Lite) from 66 to 74 weeks of age. Feed intake increased when birds
were given either 400 MUg/kg chromium or 250 mg/kg vitamin C (P < 0.05), but the
birds that received both chromium and vitamin C consumed feed similar to those
that received only chromium. Dietary treatments had no effect on egg production,
egg mass, egg volume, feed conversion ratio, and body mass (P > 0.05). The birds
that fed on diet with chromium or vitamin C produced eggs with higher shell mass
and thickness compared to the control. Both eggshell mass and thickness decreased
when vitamin C and chromium were supplemented simultaneously, and birds given the
diet supplemented with 400 MUg/kg chromium and 250 mg/kg vitamin C had eggshell
mass and thickness similar to those of the control group. The serum concentration
of chromium increased due to increasing level of dietary chromium (P < 0.05). The
birds that received diet with chromium and vitamin C had higher serum
concentrations of chromium compared to those that received only chromium (P <
0.05). Similarly, the hens that received chromium and vitamin C had higher serum
concentrations of calcium and phosphorus compared to the hens fed with other
treatments (P < 0.05). The birds given with supplemental chromium exhibited lower
serum glucose, total cholesterol, and triglycerides concentrations but higher
serum albumin and total protein concentrations compared to the other groups (P <
0.05).
PMID- 24347230
TI - It is not always necessary to do axillary dissection for T1 and T2 breast cancer-
point.
AB - Axillary lymph node dissection (ALND) has been a part of breast cancer management
since the 1900s. The idea that axillary metastases do not require surgical
removal is a repudiation of the Halstedian concept of breast cancer biology, yet
multiple prospective randomized studies show that the incidence of nodal
recurrence in patients not having ALND is substantially lower than expected,
based on the incidence of axillary metastases in patients having ALND, and
survival does not differ based on axillary treatment. Avoidance of axillary
dissection significantly reduces the morbidity of breast cancer surgery. As the
use of systemic therapy has increased and targeted therapies have become
available, the incidence of axillary recurrence in patients not having dissection
has decreased to approximately 1% at 5 years, making routine axillary dissection
difficult to justify. ALND is no longer standard management for patients with T1
and T2, clinically node-negative cancers undergoing breast-conserving therapy and
found to have a positive sentinel node, and can also be avoided in patients with
these tumor features having mastectomy if the need for postmastectomy
radiotherapy is clear with the finding of a positive sentinel node.
PMID- 24347231
TI - It is not always necessary to do axillary dissection for T1 and T2 breast cancer-
reply to point.
PMID- 24347232
TI - The need for axillary lymph node dissection in T1/T2 breast cancer surgery-
counterpoint.
AB - For breast cancer patients, the role of the axillary lymph node dissection (ALND)
in the management of clinically node negative breast cancer patient has shifted
from routine, to selective, to increasingly rare. With the publication of the
American College of Surgeons Oncology Group (ACOSOG) Z0011 trial results, some
are ready to announce the time of death of this procedure. However, many
questions remain regarding the design and statistical interpretation of the
study, the treatments the patients actually received, and its applicability in
clinical practice in light of other studies concerning regional management. Thus,
the reports of the ALND's death may be greatly exaggerated. Careful
acknowledgement of the study's strengths and shortcomings, and more recent trial
data, suggest that although ALND may be safely avoided in a subset of sentinel
lymph node positive, Z0011-eligible patients, others may require
multidisciplinary review and consensus, and a careful conversation with the
patient, before deciding it is not necessary.
PMID- 24347233
TI - The need for axillary lymph node dissection in T1/T2 breast cancer surgery--reply
to counterpoint.
PMID- 24347235
TI - Quality of care: not hospital but operator volume of pacemaker implantations
counts.
AB - Literature about pacemaker (PM) implantations shows that several clinical and
technical factors determine the short- and long-term complications after the
intervention. Annual hospital volume, however, does not negatively affect
complications in contrast with the cumulative experience of the operator. In view
of this observation, the current required number of 20 to 30 first PM
implantations for cardiology training does not match standards for quality of
care. In addition, concentration of implants and replacement of pacemakers to a
limited number of operators per hospital to comply with the increasing demands of
patients and other parties has to be seriously considered.
PMID- 24347236
TI - The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the
predictive accuracy in patients with soft tissue sarcomas.
AB - Increasing evidence indicates the involvement of inflammation and coagulation in
cancer progression and metastases. Inflammatory biomarkers hold great promise for
improving the predictive ability of existing prognostic tools in cancer patients.
In the present study, we investigated several inflammatory indices with regard to
their prognostic relevance for predicting clinical outcome in soft tissue sarcoma
(STS) patients. Three hundred and forty STS patients were divided into a training
set (n = 170) and a validation set (n = 170). Besides well-established clinico
pathological prognostic factors, we evaluated the prognostic value of the
neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the
platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well
as multivariate Cox regression models. Additionally, we developed a nomogram by
supplementing the L/M ratio to the well-established Kattan nomogram and evaluated
the predictive accuracy of this novel nomogram by applying calibration and
Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio
was significantly associated with decreased CSS and DFS (HR = 0.41, 95% CI = 0.18
0.97, p = 0.043; HR = 0.39, 95% CI = 0.16-0.91, p = 0.031, respectively) in the
training set. Using the validation set for confirmation, we found also in
multivariate analysis an independent value for CSS (HR = 0.33, 95% CI = 0.12
0.90, p = 0.03) and for DFS (HR = 0.36, 95% CI = 0.16-0.79, p = 0.01). The
estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the
L/M ratio was added. Our study reports for the first time that the pre-operative
L/M ratio represents a novel independent prognostic factor for prediction the
clinical outcome in STS patients. This easily determinable biomarker might be
helpful in improved individual risk assessment.
PMID- 24347237
TI - 3D multislab, multishot acquisition for fast, whole-brain MR elastography with
high signal-to-noise efficiency.
AB - PURPOSE: To develop an acquisition scheme for generating MR elastography (MRE)
displacement data with whole-brain coverage, high spatial resolution, and
adequate signal-to-noise ratio (SNR) in a short scan time. THEORY AND METHODS: A
3D multislab, multishot acquisition for whole-brain MRE with 2.0 mm isotropic
spatial resolution is proposed. The multislab approach allowed for the use of
short repetition time to achieve very high SNR efficiency. High SNR efficiency
allowed for a reduced acquisition time of only 6 min while the minimum SNR needed
for inversion was maintained. RESULTS: The mechanical property maps estimated
from whole-brain displacement data with nonlinear inversion (NLI) demonstrated
excellent agreement with neuroanatomical features, including the cerebellum and
brainstem. A comparison with an equivalent 2D acquisition illustrated the
improvement in SNR efficiency of the 3D multislab acquisition. The flexibility
afforded by the high SNR efficiency allowed for higher resolution with a 1.6 mm
isotropic voxel size, which generated higher estimates of brainstem stiffness
compared with the 2.0 mm isotropic acquisition. CONCLUSION: The acquisition
presented allows for the capture of whole-brain MRE displacement data in a short
scan time, and may be used to generate local mechanical property estimates of
neuroanatomical features throughout the brain.
PMID- 24347238
TI - Bioengineering virus-like particles as vaccines.
AB - Virus-like particle (VLP) technology seeks to harness the optimally tuned
immunostimulatory properties of natural viruses while omitting the infectious
trait. VLPs that assemble from a single protein have been shown to be safe and
highly efficacious in humans, and highly profitable. VLPs emerging from basic
research possess varying levels of complexity and comprise single or multiple
proteins, with or without a lipid membrane. Complex VLP assembly is traditionally
orchestrated within cells using black-box approaches, which are appropriate when
knowledge and control over assembly are limited. Recovery challenges including
those of adherent and intracellular contaminants must then be addressed. Recent
commercial VLPs variously incorporate steps that include VLP in vitro assembly to
address these problems robustly, but at the expense of process complexity.
Increasing research activity and translation opportunity necessitate
bioengineering advances and new bioprocessing modalities for efficient and cost
effective production of VLPs. Emerging approaches are necessarily multi-scale and
multi-disciplinary, encompassing diverse fields from computational design of
molecules to new macro-scale purification materials. In this review, we highlight
historical and emerging VLP vaccine approaches. We overview approaches that seek
to specifically engineer a desirable immune response through modular VLP design,
and those that seek to improve bioprocess efficiency through inhibition of
intracellular assembly to allow optimal use of existing purification technologies
prior to cell-free VLP assembly. Greater understanding of VLP assembly and
increased interdisciplinary activity will see enormous progress in VLP technology
over the coming decade, driven by clear translational opportunity.
PMID- 24347239
TI - Tandem Dyes: Stability in cocktails and compensation considerations.
AB - Background: The stability and performance of tandem conjugated antibodies can be
impaired when stored in antisera cocktails (1,2). This, and the need for frequent
re-compensation due to the possible spectral spill over variation between tandem
lots, reduces the robustness of clinical flow cytometry panels that include
tandems. Since tandems are required for standard 8-10 colour screens, further
studies of the stability of tandems in cocktails and their spill over variability
are warranted. Methods: The performance of PE- and APC-tandems stored in
cocktails was tested on fresh bone marrow, preserved blood and lyophilised cell
samples over 1-, 6- or 8-week periods respectively, and their spill over matrices
were compared. The observed correction factor differences were used as the basis
for analysing how the application of an incorrect compensation matrix could
influence data interpretation. Results: Signal intensities and background
fluorescence remained constant for all fluorochromes in the cocktails tested.
Spill over correction factors for different PE-Cy7 mAbs did not exceed or were
only marginally higher than those for non-tandem organic dye conjugated mAb. By
applying the correction factor differences observed between tandem mAb lots to
clinical data, it was found that the over and under compensation would not alter
the clinical interpretation. Conclusions: Tandems can be safely stored and used
in cocktails. However, each cocktail should be tested on relevant material prior
to use. Exact compensation settings are a requirement for accurate data. Provided
that careful evaluation of tandem compensation requirements is carried out,
certain tandems may use a generic compensation matrix. (c) 2013 Clinical
Cytometry Society.
PMID- 24347240
TI - Survival of an infant with homozygous surfactant protein C (SFTPC) mutation.
AB - Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as
autosomal traits with variable penetrance and severity or as sporadic disease
caused by a de novo mutation on one allele. Here, we report the case of a child
surviving with a homozygous surfactant protein C mutation after aggressive
clinical management unlike his six siblings who died in infancy. This
presentation raises the suspicion of an autosomal recessive inheritance that is
discussed in this report.
PMID- 24347241
TI - Therapeutic glucocorticoid administration alters the diurnal pattern of
dehydroepiandrosterone.
AB - Significant alteration in hypothalamic-pituitary-adrenal function has been
demonstrated in patients after short-term glucocorticoid therapy, but its impact
on the circadian rhythm of steroid hormones has never been investigated. This
study examined the effects of short-term prednisone administration on the diurnal
patterns of dehydroepiandrosterone (DHEA) and testosterone. Saliva samples were
collected from 11 healthy, physically active, male volunteers for DHEA and
testosterone analysis, as follows: every 4 h from 0800 to 2000 h on 2 control
days without medication, and after 1 week of oral therapeutic prednisone
treatment (60 mg daily) (days 0-3). Overall, a diurnal decline in the two steroid
hormones was observed on the control days. After short-term glucocorticoid
administration, DHEA concentrations were significantly decreased with a complete
disappearance of the DHEA diurnal pattern, which lasted 2 days post-treatment. No
glucocorticoid effect was observed for testosterone. The results indicate that
short-term prednisone treatment affects the circadian pattern of saliva DHEA but
not testosterone in healthy active volunteers. Further studies are necessary to
determine whether this alteration in DHEA circadian pattern has clinical
consequences in patients with chronic glucocorticoid therapy.
PMID- 24347242
TI - 4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated pancreatic
beta-cell apoptosis in rats with streptozotocin-induced diabetes.
AB - Endoplasmic reticulum stress (ERS) plays an important role in diabetes mellitus
(DM), but the association between DM and ERS is unknown. We have previously shown
that streptozotocin (STZ)-induced diabetes in rats is characterized by increased
levels of ERS markers. Here, we tested whether the chemical chaperone 4
phenylbutyric acid (4-PBA) ameliorated ERS-associated apoptosis in pancreatic
beta-cells in rats with STZ-induced diabetes. Male Sprague-Dawley rats were
divided into 3 groups: control group, DM group, and DM model plus 4-PBA treatment
group (4-PBA group). DM model rats were induced by injection of STZ (60 mg/kg)
intraperitoneally, and 4-PBA was administered daily by gavage at a dose of 500
mg/kg body weight for 20 days. beta-cell apoptosis was higher in the DM group
than in the control group. Moreover, the expression of caspase-3, Bax, and the
ERS indicators Bip and CHOP was markedly elevated in the pancreas of rats in the
DM group, whereas the expression of Bcl-2 was lower in these rats (P < 0.05).
Blood glucose concentration in diabetic rats gradually decreased with 4-PBA
treatment but remained higher at the end of the experiment compared to the
concentration in control rats. Consistent with this, 4-PBA raised the fasting
insulin level in diabetic rats; it also suppressed the expression of caspase-3,
Bax, and ERS indicators but enhanced the expression of Bcl-2. In conclusion, 4
PBA protects pancreatic beta-cells from apoptosis in STZ-induced diabetes by
attenuating the severity of ERS.
PMID- 24347243
TI - 17beta-Estradiol regulates scavenger receptor class BI gene expression via
protein kinase C in vascular endothelial cells.
AB - High-density lipoprotein (HDL) mediates reverse cholesterol transport. In this
process, the human homolog of the B class, type I scavenger receptor (SR-BI),
CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of
cholesterol from HDL. In endothelial cells, HDL activates endothelial nitric
oxide synthase (eNOS) via hSR-BI/CLA-1, and 17beta-estradiol (E2) modulates
nitric oxide (NO) synthesis. In this study, we elucidated the effect of E2 on hSR
BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). HSR
BI/CLA-1 expression was examined by real-time PCR, western blot analysis and
reporter gene assay in HUVECs incubated with E2. eNOS activity was assessed by
detection of phosphorylation (Ser 1179) of eNOS. We investigated the effect of
the constitutively active form or dominant negative form of protein kinase C on
hSR-BI/CLA-1 promoter activity. Our results showed that E2 increased the
endogenous expression of hSR-BI/CLA-1. E2 also enhanced the activity of the hSR
BI/CLA-1 promoter and the expression of its mRNA. However, bisindolylmaleimide I,
an inhibitor of protein kinase C, blocked the stimulatory effect of E2 on hSR
BI/CLA-1 promoter activity. Moreover, constitutively active PKC increased the
activity of the hSR-BI/CLA-1 promoter, and a dominant-negative mutant of PKC
prevented E2 from stimulating promoter activity. In cells treated with E2, HDL
stimulated the phosphorylation of serine 1179 of eNOS in HUVECs. These results
suggested that E2 upregulates the expression of the endothelial hSR-BI/CLA-1 via
the PKC pathway, which may be a novel mechanism of the anti-atherosclerotic
potential of E2 in vascular endothelial cells.
PMID- 24347245
TI - Cardiac function in 10-year-old twins following different fetal therapies for
twin-twin transfusion syndrome.
AB - OBJECTIVES: To compare cardiac function at 10 years of age in four groups of
monochorionic diamniotic (MCDA) twin pairs: uncomplicated MCDA twins (n = 6)
(Group 1); twins that had had twin-twin transfusion syndrome (TTTS) managed by
amnioreduction (TTTS-amnio, n = 9) (Group 2) or laser photocoagulation (TTTS
laser, n = 10) (Group 3); and dichorionic diamniotic controls (DCDA, n = 6)
(Group 4). METHODS: Echocardiograms optimizing apical four-chamber and short-axis
left ventricular views were stored for offline speckle-tracking analysis, blinded
to twin type. Myocardial long-axis shortening and lengthening velocities were
measured using pulsed Doppler ultrasound at the cardiac base. M-mode measurements
of fractional shortening (short axis) and maximal excursion of the
atrioventricular annulus (four-chamber) were recorded. Syngo Vector Velocity
Imaging software tracked left ventricular myocardial motion offline to produce
free wall strain, strain rate and rotation. Intertwin pair and group differences
were investigated using ANOVA. RESULTS: Cardiac measurements were within the
normal ranges for 10-year-olds. No significant within-twin-pair and intergroup
differences were found in current size, heart rates, strain or strain rate.
Compared to DCDA controls, TTTS twins showed less cardiac rotation (TTTS-laser, P
< 0.001 and TTTS-amnio, P = 0.054) with significant intertwin reduction in the ex
recipient (TTTS-amnio, P = 0.006) and larger MCDA twins (P = 0.027) compared with
their cotwins. A similar pattern was seen in left ventricular early diastolic
mitral valve tissue velocity (MVE') in all monochorionic groups, but only
achieving significance in TTTS-amnio twins (P = 0.037). Intrapair differences in
rotation and MVE' were significantly different following treatment at Quintero
stages III or IV. CONCLUSIONS: Within-twin-pair patterns of left ventricular
rotation and diastolic function differ at 10 years of age in ex-recipients of
TTTS twins treated with amnioreduction compared with those treated by laser
photocoagulation and controls. .
PMID- 24347246
TI - Identity and norms: the role of group membership in medical student wellbeing.
AB - Medical students experience high levels of mental health problems, which can lead
to poor academic performance, substance abuse and burnout. The current paper
draws on social psychology to explore the factors underpinning wellbeing in
medical students. From the literature it is evident that there is a strong
association between group membership and wellbeing. There is also evidence,
however, that when the norms of a group prescribe unhealthy behaviours, group
members who identify strongly with the group are likely to engage in those
behaviours. It was hypothesized that (a) there would be a positive relationship
between identification and wellbeing in medical students, (b) perceptions of
norms would be positively related to unhealthy behaviour which would be
negatively related to wellbeing and (c) identification would be positively
related to levels of norm-related unhealthy behaviour. Ninety-two Australian
medical students completed measures of identification, endorsement of norms, own
behaviour in relation to norms and three indicators of wellbeing. The results
supported the first hypothesis and showed only partial support for the second,
suggesting a primarily positive role of group processes in medical student
wellbeing. The implications for interventions to improve wellbeing in medical
schools and directions for future research are discussed.
PMID- 24347244
TI - Serum prolidase enzyme activity and oxidative stress levels in patients with
diabetic neuropathy.
AB - Previous studies have suggested that prolidase and nitric oxide (NO) regulate
many processes, such as collagen synthesis and matrix remodeling. Oxidative
stress plays an important role in the development of microvascular complications
in diabetic patients. Data on serum prolidase activity in patients with diabetes
mellitus or diabetic neuropathy (DN) are limited and conflicting. The aim of this
study was to measure serum prolidase activity, NO, total antioxidant status
(TAS), and malondialdehyde (MDA) levels in patients with DN. Forty-five patients
with DN and 40 healthy controls were enrolled. Serum prolidase activity, TAS,
MDA, and NO levels were determined. Serum MDA and NO levels were significantly
higher in DN patients than controls (p = 0.002, p = 0.001, respectively), while
prolidase activity and TAS levels were lower (p = 0.003, p = 0.001,
respectively). Prolidase activity was negatively correlated with NO and MDA (r =
0.911, p < 0.001; r = -0.905, p < 0.001, respectively), while positively
correlated with TAS (r = 0.981, p < 0.001) in DN patients. The current study is
the first showing the decreased serum prolidase enzyme activity. Our results
suggest that decreased collagen turnover may occur in DN patients, who have
increased oxidative stress and increased NO levels. Decreased prolidase activity
seems to be associated with increased NO levels and oxidative stress along with
decreased antioxidant levels in DN. Therefore, decreased prolidase activity may
play a role in pathogenesis of DN. Prospective clinical studies are necessary to
confirm these findings.
PMID- 24347247
TI - Methods of designing two-stage winner trials with survival outcomes.
AB - In drug development, especially for oncology studies, a recent proposal is to
combine a costly phase II dose selection study with a subsequent phase III study
into a single trial that compares the selected (winning) dose from the first
stage with the control group. This design may also be used in phase III trials,
in which the winning active treatment regimen, selected at the first stage, is
compared with the control group at the second stage. This design is known as a
two-stage winner design, as proposed by Shun et al. (2008) for continuous
outcomes. Time-to-event data are often analyzed in oncology trials. In order to
derive the critical value and power of this design, per Shun et al. (2008), it is
essential to calculate the asymptotic covariance and correlation of the log-rank
statistics for survival outcomes between the two stages. In this paper, we derive
the asymptotic covariance and correlation, and provide additional approximate
design parameters. Examples are given to illustrate the method, and simulations
are performed to evaluate the veracity of these approximate design parameters.
PMID- 24347248
TI - Clinical efficacy and safety of transcatheter closure of ruptured sinus of
valsalva aneurysm.
AB - OBJECTIVES: To evaluate the clinical efficacy and safety of transcatheter closure
(TCC) in patients with ruptured sinus of Valsalva aneurysm (RSVA). BACKGROUND:
RSVA is a rare cardiovascular disease with a varied clinical presentation. The
clinical efficacy and safety of TCC for RSVA still remain an ongoing concern.
METHODS: From January 2009 to March 2013, 22 patients with RSVA were selected for
TCC. Intracardiac pressure and size of cardiac chamber were measured before and
post TCC. All patients were followed up by transthoracic echocardiography at 1,
3, 6, 12 months after procedure. RESULTS: RSVA was successfully occluded in 20
patients (19 cases with Amplatzer duct occluder and one with muscular ventricular
septal defect occluder). Aortic root angiography showed no shunt in 18 cases and
a small residual shunt in two cases. The pressures in the right atrium, right
ventricle, and pulmonary artery were significantly decreased after the procedure
(P < 0.01), and the aortic pressure was elevated (P < 0.001). The internal
diameters of the right atrium, left atrium, and left ventricle were also
significantly declined after the procedure (P < 0.05). No complications were
found after 18.5 +/- 6.5 (range 3-35) months follow-up. Two patients underwent
acute surgical aortic valve replacement because of procedure-related aortic valve
regurgitation. CONCLUSIONS: Our results indicate that TCC is a promising
alternative therapy to surgery in appropriate patients with RSVA. However, rare
but severe procedure-related complications should be considered in the risk
assessment.
PMID- 24347250
TI - Behavioral medicine in China: history, current status, and future development.
AB - BACKGROUND: Behavioral medicine in China has developed quickly in the last three
decades. PURPOSE: We briefly summarized the history, the main scope and
achievements, and the future development of behavioral medicine in China. METHOD:
We did a literature search and discussed with senior scholars in behavioral
medicine in China. RESULTS: The concept and main scope of behavioral medicine in
China have been developed largely in accordance with the international
perspective. Research in behavioral medicine in China significantly contributed
to the better understanding of the relationship between various health behavioral
factors and psychosomatic disorders and possible mechanisms of this relationship.
The following aspects will be the main areas to be further developed in
behavioral medicine in China: (1) Basic theories of behavioral medicine and
theoretical mechanisms of higher nervous activities in human behavior regulation.
(2) Etiology, pathogenesis, and mechanisms of common diseases that are closely
related to human lifestyle behaviors. (3) Assessment criteria for unhealthy and
disease-related behaviors. (4) Behavioral therapy of psychosomatic disorders, and
rehabilitation technologies of disability. (5) Application of major findings from
research of behavioral medical science in clinical practice and in health
promotion of the whole society. CONCLUSION: Behavioral medicine in China, as a
multidisciplinary subject, plays a relevant role in preventing behavior-related
psychosomatic diseases and in promoting health of the public.
PMID- 24347249
TI - Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate
cancer cells by targeting adherens junction molecules.
AB - Hypoxic conditions in prostate cancer (PCA) are associated with poor prognosis;
however, precise mechanism/s through which hypoxia promotes malignant phenotype
remains unclear. Here, we analyzed the role of exosomes from hypoxic PCA cells in
enhancing the invasiveness and stemness of naive PCA cells, as well as in
promoting cancer-associated fibroblast (CAF) phenotype in prostate stromal cells
(PrSC). Human PCA LNCaP and PC3 cells were exposed to hypoxic (1% O2 ) or
normoxic (21% O2 ) conditions, and exosomes secreted under hypoxic (Exo(Hypoxic)
) and normoxic (Exo(Normoxic) ) conditions were isolated from conditioned media.
Nanoparticle tracking analysis revealed that Exo(Hypoxic) have smaller average
size as compared to Exo(Normoxic) . Immunoblotting results showed a higher level
of tetraspanins (CD63 and CD81), heat shock proteins (HSP90 and HSP70), and
Annexin II in Exo(Hypoxic) compared to Exo(Normoxic) . Co-culturing with
Exo(Hypoxic) increased the invasiveness and motility of naive LNCaP and PC3
cells, respectively. Exo(Hypoxic) also promoted prostasphere formation by both
LNCaP and PC3 cells, and enhanced alpha-SMA (a CAF biomarker) expression in PrSC.
Compared to Exo(Normoxic) , Exo(Hypoxic) showed higher metalloproteinases
activity and increased level of diverse signaling molecules (TGF-beta2,
TNF1alpha, IL6, TSG101, Akt, ILK1, and beta-catenin). Furthermore, proteome
analysis revealed a higher number of proteins in Exo(Hypoxic) (160 proteins)
compared to Exo(Normoxic) (62 proteins), primarily associated with the remodeling
of epithelial adherens junction pathway. Importantly, Exo(Hypoxic) targeted the
expression of adherens junction proteins in naive PC3 cells. These findings
suggest that Exo(Hypoxic) are loaded with unique proteins that could enhance
invasiveness, stemness, and induce microenvironment changes; thereby, promoting
PCA aggressiveness.
PMID- 24347251
TI - Mediation of smoking consumption on the association of perception of smoking
risks with successful spontaneous smoking cessation.
AB - BACKGROUND: The perception of smoking risks has positive and smoking consumption
has negative effects on successful smoking cessation, but no information is now
available for what is the role of smoking consumption on the relationship between
perception of smoking risks and successful smoking cessation. PURPOSE: To assess
the mediation of smoking amount on the association of perception of smoking risks
with successful spontaneous smoking cessation. METHOD: A community-based case
control study was conducted with 294 adult spontaneous successful smoking
quitters who have been quitting smoking consecutively for more than 2 years as
the cases, and 347 adult failed spontaneous smoking quitters who quitted but
relapsed or have been quitting smoking continuously equal to or less than 2 years
as the controls. The smoking amount was evaluated by pack-year that was
categorized into tertiles and scored inversely. The score of perception of
smoking risks was also categorized into tertiles. Propensity score as the
covariate in the regression model was used to adjust the potential confounding.
The total effect was decomposed into direct effect and indirect (mediating)
effect by using logistic regression based on the KHB method proposed by Karlson,
Holm, and Breen. The proportion of mediating effect among the total effect is
calculated as the indirect effect divided by the total effect. RESULTS: After
adjusting age, profession, education, marital status, and reasons for quitting
smoking by using propensity score, the small mediating effect of smoking amount
on the association of perception of smoking risks with successful spontaneous
smoking cessation was observed, and the mediating effect of smoking amount was
23.75% among the total effect. The dose-response analysis showed that the
mediating effect of smoking amount in the groups with middle and high score of
perception of smoking risks were 10.15 and 37.84% among their total effect,
respectively. CONCLUSION: This study reveals that smoking amount has only small
mediating effect among the total effect of perception of smoking risks on the
successful spontaneous smoking cessation; enhancing the smokers' perception of
smoking risks could promote their attempt to reduce smoking, so as to increase
the probability of successful smoking cessation.
PMID- 24347252
TI - Exact Equations for SIR Epidemics on Tree Graphs.
AB - We consider Markovian susceptible-infectious-removed (SIR) dynamics on time
invariant weighted contact networks where the infection and removal processes are
Poisson and where network links may be directed or undirected. We prove that a
particular pair-based moment closure representation generates the expected
infectious time series for networks with no cycles in the underlying graph.
Moreover, this "deterministic" representation of the expected behaviour of a
complex heterogeneous and finite Markovian system is straightforward to evaluate
numerically.
PMID- 24347253
TI - Travelling waves in hybrid chemotaxis models.
AB - Hybrid models of chemotaxis combine agent-based models of cells with partial
differential equation models of extracellular chemical signals. In this paper,
travelling wave properties of hybrid models of bacterial chemotaxis are
investigated. Bacteria are modelled using an agent-based (individual-based)
approach with internal dynamics describing signal transduction. In addition to
the chemotactic behaviour of the bacteria, the individual-based model also
includes cell proliferation and death. Cells consume the extracellular nutrient
field (chemoattractant), which is modelled using a partial differential equation.
Mesoscopic and macroscopic equations representing the behaviour of the hybrid
model are derived and the existence of travelling wave solutions for these models
is established. It is shown that cell proliferation is necessary for the
existence of non-transient (stationary) travelling waves in hybrid models.
Additionally, a numerical comparison between the wave speeds of the continuum
models and the hybrid models shows good agreement in the case of weak chemotaxis
and qualitative agreement for the strong chemotaxis case. In the case of slow
cell adaptation, we detect oscillating behaviour of the wave, which cannot be
explained by mean-field approximations.
PMID- 24347254
TI - Independent predictors of human milk receipt at neonatal intensive care unit
discharge.
AB - OBJECTIVE: The aim of this study is to construct a predictive model for very low
birth weight (VLBW) infants' receipt of mother's own milk within 24 hours before
neonatal intensive care unit (NICU) discharge. STUDY DESIGN: Vermont Oxford
Network (VON) clinical data were analyzed retrospectively for VLBW infants
admitted between 2002 and 2012 at an inner city, level IV NICU with a well
established lactation program. Bivariate analyses compared infant characteristics
between recipients and nonrecipients of human milk before 24 hours of NICU
discharge. Independent predictors identified in the bivariate analyses (p <=
0.05), were eligible for inclusion into a multivariable logistic regression
model. RESULTS: We observed a 60.4% human milk feeding rate at NICU discharge.
Multiple independent maternal (black race and Hispanic ethnicity) and clinical
factors (need for mechanical ventilation, patent ductus arteriosus, late-onset
sepsis, or discharge to home on a cardiorespiratory monitor) positively predicted
the outcome. CONCLUSIONS: Our results were inconsistent with previous studies and
suggest that a strong NICU lactation program in combination with a community
based peer counselor program may increase rates of human milk receipt among VLBW
infants born to black/Hispanic mothers and those with more complicated neonatal
courses.
PMID- 24347255
TI - High aspartate aminotransferase level predicts poor neurodevelopmental outcome in
infants with meconium aspiration syndrome.
AB - OBJECTIVE: The aim of our study is to clarify the perinatal predictive factors of
meconium aspiration syndrome (MAS) with neurodevelopmental delay (ND) in infants.
MATERIALS AND METHODS: In this retrospective study, data were collected from the
infants born between 1990 and 2008. They all had primary diagnosis of MAS.
Multivariable analyzed perinatal predictive factors of MAS with ND. The
developmental status of these infants was followed at least 2 years with the
Wechsler Intelligence Scale for Children. RESULTS: A total of 114 surviving
babies met the criteria of MAS. Six babies were defined as ND group. Lower 5
minute Apgar score and diastolic blood pressure were significantly related to the
ND group. Elevated asparatate aminotransferase (AST), nucleated red blood cells,
and white blood cells at the time of admission were significantly high in ND
group. Furthermore, AST had area under the receiver operating characteristic
curve of 0.879, (95% confidence interval: 0.801, 0.934), p < 0.0001. At 96 mg/dL,
it had 83.33% sensitivity, 80.81% specificity, and negative predictive value of
98.8. Multivariable logistic regression analysis revealed AST was the only
significant predictive factor for MAS with ND. CONCLUSION: Early intervention
should be recommended in infants having MAS with high AST level at birth for
improving their neurodevelopmental outcomes.
PMID- 24347256
TI - Changes in premature infant mercury and lead blood levels after blood
transfusions.
AB - OBJECTIVE: To describe the blood level changes of mercury and lead after packed
red blood cell (PRBC) transfusions in <= 750 g birth weight infants. STUDY
DESIGN: Heavy metal blood levels were measured in infants in PRBC units on 1st,
4th, 5th, and 7th days (D1, D4, D5, and D7) of life and in urine on D1, D4, and
D7. RESULTS: A total of 10 infants were enrolled with a mean birth weight of 632
+/- 72 g. Out of which nine infants received one or more PRBC transfusions, with
an average of 2.9 +/- 2.5 transfusions per infant. Heavy metals were detected in
all the transfusions. The average mercury level was 1.33 ug/L on D1 and 1.66 ug/L
on D7, p > 0.05. The average lead level was 0.32 ug/dL on D1 and 0.56 ug/dL on
D7, p > 0.05. Urinary mercury excretion increased in infants with no bowel
movements. Urinary excretion of lead decreased over time as blood levels
increased. CONCLUSIONS: After receiving blood transfusions, the blood levels of
mercury and lead were maintained at the end of the 1st week of life. As there is
no evidence of a proportionate increase in excretory amounts of these heavy
metals, there is a concern that they are retained and potentially exert toxic
effects.
PMID- 24347258
TI - The adjusted effect of maternal body mass index, energy and macronutrient intakes
during pregnancy, and gestational weight gain on body composition of full-term
neonates.
AB - OBJECTIVE: To evaluate the effect of prepregnancy body mass index (BMI), energy
and macronutrient intakes during pregnancy, and gestational weight gain (GWG) on
the body composition of full-term appropriate-for-gestational age neonates. STUDY
DESIGN: This is a cross-sectional study of a systematically recruited convenience
sample of mother-infant pairs. Food intake during pregnancy was assessed by food
frequency questionnaire and its nutritional value by the Food Processor Plus
(ESHA Research Inc, Salem, OR). Neonatal body composition was assessed both by
anthropometry and air displacement plethysmography. Explanatory models for
neonatal body composition were tested by multiple linear regression analysis.
RESULTS: A total of 100 mother-infant pairs were included. Prepregnancy
overweight was positively associated with offspring weight, weight/length, BMI,
and fat-free mass in the whole sample; in males, it was also positively
associated with midarm circumference, ponderal index, and fat mass. Higher energy
intake from carbohydrate was positively associated with midarm circumference and
weight/length in the whole sample. Higher GWG was positively associated with
weight, length, and midarm circumference in females. CONCLUSION: Positive
adjusted associations were found between both prepregnancy BMI and energy intake
from carbohydrate and offspring body size in the whole sample. Positive adjusted
associations were also found between prepregnancy overweight and adiposity in
males, and between GWG and body size in females.
PMID- 24347259
TI - The timing of adverse events with Foley catheter preinduction cervical ripening;
implications for outpatient use.
AB - OBJECTIVE: We sought to determine the rate and timing of adverse events that
occur during preinduction cervical ripening using the Foley catheter before
extrusion of the balloon and institution of oxytocin. STUDY DESIGN: Using
electronic medical records, we identified all women who presented for
preinduction cervical ripening using a Foley catheter with a term (>=37 weeks)
singleton vertex live fetus from January 1, 2006, to June 14, 2009. Women were
excluded if they had had a previous cesarean delivery, gestational hypertension
or preeclampsia, pregestational diabetes, rupture of membranes before induction,
fetal anomaly, or antepartum stillbirth. Outcomes were cesarean delivery for
nonreassuring fetal tracing, vaginal bleeding, placental abruption, or
intrapartum stillbirth occurring between 2 hours after Foley catheter placement
and 6 am. RESULTS: Among 2,514 women, 1,905 met the inclusion criteria. No
adverse outcomes were noted among term, singleton uncomplicated pregnancies
receiving a Foley catheter for preinduction cervical ripening who met inclusion
criteria (relative risk, 0.0; 95% confidence interval, 0.0-0.002). CONCLUSIONS:
In a low-risk population, the use of the Foley catheter for preinduction cervical
ripening was associated with no adverse outcomes. It appears to be a safe
mechanism for cervical ripening and has the potential for use in the outpatient
setting in a selected subset of women.
PMID- 24347260
TI - Changes in fetal heart tracing characteristics after magnesium exposure.
AB - OBJECTIVE: The aim of this study is to describe the changes in term fetal heart
tracings after magnesium exposure. MATERIALS AND METHODS: This was a
retrospective cohort study of consecutive women delivering at a gestational age
of >= 37 weeks with severe preeclampsia, receiving magnesium for seizure
prophylaxis. Overall 90 minutes of electronic fetal monitoring (30 before
magnesium, 30 during magnesium bolus, and 30 during steady state infusion) was
prospectively interpreted by formally trained and blinded research nurses using
American Congress of Obstetricians and Gynecologists guidelines. Multivariable
analyses were performed using generalized estimating equations, comparing
preexposure patterns to bolus, and steady state. RESULTS: Out of the 238 women
evaluated, an average decrease of 2.4 beats per minute (p = 0.02) was found after
magnesium bolus. This persisted into the steady state (p < 0.01). Minimal/absent
variability increased during bolus infusion (odds ratio [OR] 2.40, 95% confidence
interval [CI] 1.10-5.62) but corrected by steady state (OR 1.44, 95% CI 0.76
2.80). There were no significant changes in the fetal heart rate (FHR) baseline <
120, tachycardia, or presence of accelerations or decelerations. CONCLUSION:
Exposure to magnesium is associated with a transient decrease in variability and
a clinically insignificant decrease in FHR baseline without an increased
incidence in bradycardia or category change.
PMID- 24347261
TI - Unintended extension of the lower segment uterine incision at cesarean delivery:
a randomized comparison of sharp versus blunt techniques.
AB - OBJECTIVE: This study compared two methods of expanding the uterine incision at
the time of cesarean delivery, which is associated with the risk of unintended
extension. STUDY DESIGN: This randomized trial included 1,076 women who underwent
elective cesarean delivery. The primary outcome measure was the incidence of
unintended extension related to the method used for expanding the uterine
incision. RESULTS: Participants in both groups (blunt vs. sharp) had similar
demographic and clinical characteristics. The incidence of unintended extension
(8.8% vs. 4.8%; p = 0.009), mean estimated blood loss (853.67 +/- 42 mL vs.
664.80 +/- 38 mL; p = 0.001), and blood loss >1000 mL (11.4% vs. 6.8%; p = 0.009)
was significantly higher in the sharp group compared with the blunt group. No
difference in transfusions (7.5% vs. 6.3%; p = 0.440) or the need for additional
supertonic agents (16% vs. 12.9%; p = 0.144) was noted. CONCLUSION: Sharp
expansion of the uterine incision was related to a higher risk of unintended
extension and maternal blood loss. Because blunt expansion is associated with a
lower risk for unintended extension and maternal blood loss, it should be the
first option during elective cesarean delivery.
PMID- 24347257
TI - Adverse pregnancy outcomes among women with prior spontaneous or induced
abortions.
AB - OBJECTIVE: The aim of the article is to determine whether prior spontaneous
abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are
associated with subsequent adverse pregnancy outcomes in nulliparous women.
METHODS: We performed a secondary analysis of data collected from nulliparous
women enrolled in a completed trial of vitamins C and E or placebo for
preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal
outcomes were determined for nulliparous women with prior SABs and IABs as
compared with primigravid participants. RESULTS: Compared with primigravidas,
women with one prior SAB were at increased risk for perinatal death (adj. OR,
1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated
with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI,
1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI,
1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one
previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9)
and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than
6 months after SAB was not associated with adverse outcomes. CONCLUSION:
Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at
increased risk for adverse pregnancy outcomes.
PMID- 24347263
TI - Depressed heart rate variability is associated with abnormal EEG, MRI, and death
in neonates with hypoxic ischemic encephalopathy.
AB - OBJECTIVE: Asphyxia can lead to autonomic nervous system dysfunction, including
depressed heart rate variability (HRV). We tested the hypothesis that low HRV is
associated with adverse short-term outcomes of abnormalities on
electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) and death
in neonates with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Neonates
undergoing hypothermia therapy for HIE underwent monitoring of HRV. HRV in the
first day after birth and after hypothermia and rewarming (days 4-7) were
analyzed in relation to death and severity of abnormal findings on EEG and MRI.
RESULTS: A total of 37 neonates had data available in the first 24 hour after
birth and 67 had data days 2 to 7. Depressed HRV was significantly associated
with adverse outcomes of death or moderate-to-severe abnormalities on EEG or MRI.
In the first 24 hours, the odds ratio (OR) of one or more adverse outcomes for
every 10-millisecond decrease in HRV was 3.19 (95% CI, 1.3-7.8; p = 0.01). HRV
improved over time but low HRV remained significantly associated with adverse
outcomes days 4 to 7 (OR, 2.72; CI, 1.32-5.61; p < 0.01). CONCLUSIONS: Monitoring
HRV, which is reflected in the heart rate characteristic index, may provide
useful adjunct information on the severity of brain injury in infants with HIE.
PMID- 24347262
TI - Medication use in the neonatal intensive care unit.
AB - OBJECTIVE: The aim of the article is to provide an update on medication use in
infants admitted to the neonatal intensive care unit (NICU) in the United States
and examine how use has changed over time. STUDY DESIGN: We performed a
retrospective review (2005-2010) of a large prospectively collected
administrative database. RESULT: Medications most commonly administered during
the study period were ampicillin, gentamicin, caffeine citrate, vancomycin,
beractant, furosemide, fentanyl, dopamine, midazolam, and calfactant (56-681
exposures per 1,000 infants). Those with the greatest relative increase in use
included azithromycin, sildenafil, and milrinone. Medications with the greatest
relative decrease in use included theophylline, metoclopramide, and doxapram.
CONCLUSION: Medication use in the NICU has changed substantially over time, and
only 35% of the most commonly prescribed medications are Food and Drug
Administration -approved in infants.
PMID- 24347264
TI - In utero stem cell transplantation for radical treatment of osteogenesis
imperfecta: perspectives and controversies.
AB - Osteogenesis imperfecta (OI) is a lethal hereditary connective tissue disease
that affects the synthesis of type I collagen. Current treatment options
including surgical, physical, and medical treatment help to reduce pain,
deformities, and rate of bone fracture. However, these choices are insufficient
and are associated with many adverse effects. The development of stem cell
therapy allows scientists to consider this option for radical treatment of many
genetic diseases including OI. In utero stem cell transplantation provides a
better opportunity for early prenatal intervention while the fetus is preimmune
and before any permanent damage occurs. Few animal and human trials for treatment
of OI have been published, and the results were promising but still
controversial. Our objective is to review the available evidence and discuss the
points of controversy including the parameters of treatment success and postnatal
predictors of long-term treatment outcome.
PMID- 24347265
TI - Simultaneous dual contrast weighting using double echo rapid acquisition with
relaxation enhancement (RARE) imaging.
AB - PURPOSE: This work proposes a dual contrast rapid acquisition with relaxation
enhancement (RARE) variant (2in1-RARE), which provides simultaneous proton
density (PD) and T2 * contrast in a single acquisition. THEORY AND METHODS: The
underlying concept of 2in1-RARE is the strict separation of spin echoes and
stimulated echoes. This approach offers independent weighting of spin echoes and
stimulated echoes. 2in1-RARE was evaluated in phantoms including signal-to-noise
ratio (SNR) and point spread function assessment. 2in1-RARE was benchmarked
versus coherent RARE and a split-echo RARE variant. The applicability of 2in1
RARE for brain imaging was demonstrated in a small cohort of healthy subjects (n
= 10) and, exemplary, a multiple sclerosis patient at 3 Tesla as a precursor to a
broader clinical study. RESULTS: 2in1-RARE enables the simultaneous acquisition
of dual contrast weighted images without any significant image degradation and
without sacrificing SNR versus split-echo RARE. This translates into a factor of
two speed gain over multi-contrast, sequential split-echo RARE. A 15% broadening
of the point spread function was observed in 2in1-RARE. T1 relaxation effects
during the mixing time can be neglected for brain tissue. CONCLUSION: 2in1-RARE
offers simultaneous acquisition of images of anatomical (PD) and functional (T2
*) contrast. It presents an alternative to address scan time constraints
frequently encountered during sequential acquisition of T2 * or PD-weighted RARE.
PMID- 24347266
TI - Tumor-derived microparticles induce bone marrow-derived cell mobilization and
tumor homing: a process regulated by osteopontin.
AB - Acute chemotherapy can induce rapid bone-marrow derived pro-angiogenic cell
(BMDC) mobilization and tumor homing, contributing to tumor regrowth. To study
the contribution of tumor cells to tumor regrowth following therapy, we focused
on tumor-derived microparticles (TMPs). EMT/6 murine-mammary carcinoma cells
exposed to paclitaxel chemotherapy exhibited an increased number of TMPs and
significantly altered their angiogenic properties. Similarly, breast cancer
patients had increased levels of plasma MUC-1(+) TMPs following chemotherapy. In
addition, TMPs from cells exposed to paclitaxel induced higher BMDC mobilization
and colonization, but had no increased effect on angiogenesis in Matrigel plugs
and tumors than TMPs from untreated cells. Since TMPs abundantly express
osteopontin, a protein known to participate in BMDC trafficking, the impact of
osteopontin-depleted TMPs on BMDC mobilization, colonization, and tumor
angiogenesis was examined. Although EMT/6 tumors grown in mice inoculated with
osteopontin-depleted TMPs had lower numbers of BMDC infiltration and microvessel
density when compared with EMT/6 tumors grown in mice inoculated with wild-type
TMPs, no significant difference in tumor growth was seen between the two groups.
However, when BMDCs from paclitaxel-treated mice were injected into wild-type
EMT/6-bearing mice, a substantial increase in tumor growth and BMDC infiltration
was detected compared to osteopontin-depleted EMT/6-bearing mice injected with
BMDCs from paclitaxel-treated mice. Collectively, our results suggest that
osteopontin expressed by TMPs play an important role in BMDC mobilization and
colonization of tumors, but is not sufficient to enhance the angiogenic activity
in tumors.
PMID- 24347267
TI - Influence of physical activity on T1 and T2* relaxation times of healthy Achilles
tendons at 3T.
AB - PURPOSE: To evaluate longitudinal (T1) and transverse (T2*) relaxation times at
different Achilles tendon locations (insertion, mid-portion, and musculotendinous
area) in a cohort of subjects with variable tendon straining activity, but
without any signs of tendinopathy. MATERIALS AND METHODS: T1 and T2* relaxation
times of the Achilles tendon were measured using an ultrashort echo time (UTE)
imaging sequence with flip angle and echo time variation on a 3T whole-body
clinical magnetic resonance (MR) scanner. Twenty-four tendons of 12 healthy
volunteers and 18 tendons of nine healthy recreational long-distance runners
(average weekly running distance of 47.4 +/- 5.3 km) were enrolled. RESULTS: Mean
T1 values of the whole tendon showed no marked group differences, whereas T2*
relaxation times of runners were significantly longer (mean percentage increase
15.7 +/- 4.9%; P = 0.0181) compared to controls. Regarding group differences for
the investigated insertional, mid-portion, and musculotendinous area of the
Achilles tendon, only the mid-portion of the Achilles tendon in the running group
presented significantly longer T2* values (mean percentage increase 29.1 +/-
23.0%; P = 0.0420) in comparison to the control group. CONCLUSION: Prolonged T2*
values especially in the mid-portion of the Achilles tendon of runners are likely
to reflect an adaptation of the tendon microstructure to repetitive tendon
straining activity.
PMID- 24347268
TI - Controlled interfacial electron dynamics in highly efficient Zn2 SnO4 -based dye
sensitized solar cells.
AB - Among ternary oxides, Zn2 SnO4 (ZSO) is considered for dye-sensitized solar cells
(DSSCs) because of its wide bandgap, high optical transmittance, and high
electrical conductivity. However, ZSO-based DSSCs have a poor performance record
owing largely to the absence of systematic efforts to enhance their performance.
Herein, general strategies are proposed to improve the performance of ZSO-based
DSSCs involving interfacial engineering/modification of the photoanode. A
conformal ZSO thin film (blocking layer) deposited at the fluorine-doped tin
oxide-electrolyte interface by pulsed laser deposition suppressed the back
electron transfer effectively while maintaining a high optical transmittance,
which resulted in a 22 % improvement in the short-circuit photocurrent density.
Surface modification of ZSO nanoparticles (NPs) resulted in an ultrathin ZnO
shell layer, a 9 % improvement in the open-circuit voltage, and a 4 % improvement
in the fill factor because of the reduced electron recombination at the ZSO NPs
electrolyte interface. The ZSO-based DSSCs exhibited a faster charge injection
and electron transport than their TiO2 -based counterparts, and their superior
properties were not inhibited by the ZnO shell layer, which indicates their
feasibility for highly efficient DSSCs. Each interfacial engineering strategy
could be applied to the ZSO-based DSSC independently to lead to an improved
conversion efficiency of 6 %, a very high conversion efficiency for a non-TiO2
based DSSC.
PMID- 24347269
TI - Metallic oxide nanoparticles stimulate blood coagulation independent of their
surface charge.
AB - Positively charged metallic oxides prevent blood coagulation whereas negatively
charged metallic oxides are thrombogenic. This study was performed to examine
whether this effect extends to metallic oxide nanoparticles. Oscillation shear
rheometry was used to study the effect of zinc oxide and silicon dioxide
nanoparticles on thrombus formation in human whole blood. Our data show that
oscillation shear rheometry is a sensitive and robust technique to analyze
thrombogenicity induced by nanoparticles. Blood without previous contact with
nanoparticles had a clotting time (CT) of 16.7 +/- 1.0 min reaching a maximal
clot strength (CS) of 16 +/- 14 Pa (G') after 30 min. ZnO nanoparticles (diameter
70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8
+/- 3.6 min and provoked a weak clot (CS 1.5 +/- 1.0 Pa). However, at a lower
concentration of 100 ug/mL the ZnO particles dramatically reduced CT to 6.0 +/-
0.5 min and increased CS to 171 +/- 63 Pa. This procoagulant effect decreased at
lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles
(diameter 232 nm, -28 mV zeta-potential) at high concentrations (1 mg/mL) reduced
CT (2.1 +/- 0.2 min) and stimulated CS (249 +/- 59 Pa). Similar to ZnO particles,
this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in
high concentrations reproduce the surface charge effects on blood coagulation
previously observed with large particles or solid metal oxides. However,
nanoparticles with different surface charges equally well stimulate coagulation
at lower concentrations. This stimulation may be an effect which is not directly
related to the surface charge.
PMID- 24347270
TI - Dielectrophoresis with 3D microelectrodes fabricated by surface tension assisted
lithography.
AB - This paper demonstrates the utilization of 3D semispherical shaped
microelectrodes for dielectrophoretic manipulation of yeast cells. The
semispherical microelectrodes are capable of producing strong electric field
gradients, and in turn dielectrophoretic forces across a large area of channel
cross-section. The semispherical shape of microelectrodes avoids the formation of
undesired sharp electric fields along the structure and also minimizes the
disturbance of the streamlines of nearby passing fluid. The advantage of
semispherical microelectrodes over the planar microelectrodes is demonstrated in
a series of numerical simulations and proof-of-concept experiments aimed toward
immobilization of viable yeast cells.
PMID- 24347271
TI - A novel condition for capillary electrophoretic analysis of reductively aminated
saccharides without removal of excess reagents.
AB - We have identified novel CE conditions for the separation of 7-amino-4
methylcoumarin-labeled monosaccharides and oligosaccharides from glycoproteins.
Using a neutrally coated capillary and alkaline borate buffer containing
hydroxypropylcellulose and ACN, saccharide derivatives form anionic borate
complexes, which move from the cathode to the anode in an electric field and are
detected near the anodic end. Excess labeling reagents and other fluorescent
products remain at the cathodic end. Fluorimetric detection using an LED as a
light source enables determination of monosaccharide derivatives with good
linearity between at least 0.4 and 400 MUM, may correspond to 140 amol to 140
fmol. The lower LOD (S/N = 5) is only 80 nM in the sample solution (ca. 28 amol).
The results were comparable to reported values using fluorometric detection LC.
The method was also applied to the analysis of oligosaccharides that were
enzymatically released from glycoproteins. Fine resolution enables profiling of
glycans in glycoproteins. The applicability of the method was examined by
applying it to other derivatives labeled with nonacidic tags such as ethyl p
aminobenzoate- and 2-aminoacridone-labeled saccharides.
PMID- 24347272
TI - An optimized method to extract poplar leaf proteins for two-dimensional gel
electrophoresis guided by analysis of polysaccharides and phenolic compounds.
AB - Commonly used methods for protein extraction from plant leaves, such as
extraction with phenol or a combination of trichloroacetic acid and acetone, were
ineffective for four tested cultivars of poplar. Moreover, multiple protocols for
2DE of the extracted proteins gave different results when protein profiles of
relatively closely related plants were compared. Given that polycyclic compounds
strongly hinder 2DE, we analyzed the impact of polyphenols and polysaccharides
present in the plant tissues used for protein extraction, on the quality of 2DE
protein profiles. Analysis of content of polyphenols and polysaccharides in
leaves of poplar cultivars showed that even small differences in concentrations
of analyzed metabolites accompany large differences between poplar cultivars when
considering the susceptibility of samples to protein extraction for 2DE. High
quality 2DE results were correlated with decreased amounts of polyphenols.
Additional analysis using MS/MS suggested that only levels of total phenolics
affected the results of 2DE. Soluble total nonstructural carbohydrates also had a
negative effect, but the level of starch was not important. Finally, we present
an optimized method for extraction of proteins from poplar leaves, which enables
reliable comparative analysis of four different poplar cultivars, that is,
"Eridano," "Villafranca," "NE-42," and "Luisa Avanzo," which have not yet been
used for the proteomic studies.
PMID- 24347277
TI - Replication-defective HSV-1 effectively targets trigeminal ganglion and inhibits
viral pathopoiesis by mediating interferon gamma expression in SH-SY5Y cells.
AB - It has been widely believed that recurrence of herpes simplex keratitis (HSK) is
due to the reactivation of herpes simplex virus type 1 (HSV-1) from latent sites
in trigeminal ganglion (TG). However, there are also not effective vectors which
could target TG for therapy. Replication-defective HSV-1 vector (rdHSV-IFNgamma)
was established by calcium phosphate co-transfection of complementing cells. We
firstly infected rdHSV-IFNgamma to SH-SY5Y, and detected IFNgamma expression by
western blot, evaluated 50 % cellular cytotoxicity (CC(50)) by ELISA. Antiviral
activity of rdHSV-IFNgamma was examined by immunofluorescence and antiviral
concentration of 50 % effectiveness (EC(50)) assay. The rdHSV-IFNgamma vector was
immunized to Wistar rats to observe targeting function to TG. Kaplan-Meier
survival analysis was utilized to assess security of rdHSV-IFNgamma. RT-PCR and
immunohistochemistry assay were employed to detect rdHSV-IFNgamma localization in
TG. Western blot was employed to detect IFNgamma expression. rdHSV-IFNgamma was
successfully established, and performed an effective antiviral activity and
higher security in SH-SY5Y. There were no significant differences of survival and
corneal infection rate of rdHSV-IFNgamma immunized rats among groups (P > 0.05).
RT-PCR and immunohistochemistry indicated that expression of glycoprotein D (gD)
in TG could target TG and decreased following with times post immunization.
Furthermore, IFNgamma was expressed effectively in TG tissues. Our findings
indicated that established rdHSV-IFNgamma vector effectively transported
therapeutic gene into TG tissues. The administration of replication-defective
vector carrying therapeutic genes may become a promising tool in inhibition or
reoccurrence of HSK in clinical.
PMID- 24347278
TI - Surgical salvage of acute renal artery occlusion in the setting of a solitary
kidney.
AB - Management of acute renal artery occlusion in patients with a solitary kidney has
a poorly defined prognosis. Loss of renal function is reported by some when acute
warm ischemia reaches 2 hours. We report a unique case of a patient that had a 24
hour onset of anuria and acute renal failure upon arrival to the hospital.
Nuclear imaging showed trace uptake of the right kidney, without evidence of
excretion. Conventional digital subtraction angiography was performed; however,
evidence of nephrogram or distal filling of the renal artery was not
demonstrated. Secondary to conflicting studies, a computed tomography of the
abdomen and pelvis with intravenous contrast revealed only minimal cortical
perfusion despite complete occlusion of the previously grafted right renal
artery. Patient was taken for urgent hepatorenal bypass surgery. Intraoperative
return of urine output occurred immediately after completion of the bypass.
Hemodialysis, which was required preoperatively, was stopped after <30 days of
bypass procedure. Over 2 years following successful renal salvage, the patient
has maintained a normal glomerular filtration rate and patency of her bypass by
duplex follow-up.
PMID- 24347279
TI - Endovascular management of a mobile thoracic aortic thrombus following recurrent
distal thromboembolism: a case report and literature review.
AB - Sources of lower extremity and visceral arterial thromboembolism most commonly
include the heart and proximal aneurysmal disease. Infrequently, further workup
of "cryptogenic" emboli will reveal a mural atheroma or thrombus of the
descending thoracic aorta. Without prospective data, anticoagulation and open
surgical thrombectomy with or without aortic replacement have been the standard
approach. Presented is a case of a floating mural thrombus in the setting of
superior mesenteric and femoral arterial thromboembolism that was effectively
treated with endovascular stent graft exclusion.
PMID- 24347280
TI - Statins promote residual aneurysm sac regression following endovascular aortic
aneurysm repair.
AB - BACKGROUND: Regression of the residual sac is indicative of successful
endovascular aortic aneurysm (EVAR) repair. Using color duplex ultrasound (CDU),
we monitored the residual aneurysm sac following EVAR and correlated sac behavior
with perioperative risk factors. METHODS: Of 145 patients with EVAR, 106 (73.1%)
patients between January 01, 2003, and July 01, 2010, had at least 2 consecutive
postoperative scans and thus were eligible for inclusion. Mean (+/- standard
deviation [SD]) CDU scans per person was 4.6 (+/- 1.4). All were conducted by the
same technologist using a standard protocol on the same machine. Aneurysm sac
change in centimeters and percentage terms was calculated. The presence or
absence of an endoleak was also recorded. Change in aneurysm sac size was
correlated with preoperative risk factors. FINDINGS: Mean sac size change at 1
month was a decrease of 0.24 cm, equating to a percentage change of 4.3%. At 7
months, the decrease was 0.59 cm (9.8%), at 12 months, 0.73 cm (12.4%), at 18
months 0.92 cm (15.8%), and at 36 months 1.0 cm (16.6%). Both univariate and
multivariate analyses demonstrated that statin therapy (P = .002) was the only
risk factor variable positively associated with aneurysm regression while the
presence of an endoleak was inversely related to sac reduction (P = .01).
INTERPRETATION: Maximum aneurysmal sac reduction seems to occur in the first year
following endograft implantation. Statin therapy appears to be associated with an
increased likelihood of sac regression following EVAR. Further investigation of
the role of statins in the biology of abdominal aortic aneurysmal disease is
warranted.
PMID- 24347281
TI - Gender and outcomes of carotid artery interventions.
AB - The benefits of carotid artery revascularization in women have been debated since
the publication of large randomized clinical trials comparing carotid
endarterectomy (CEA) to medical therapy. Institutional series have historically
had an underrepresentation of women and/or have lacked power for adequate
analysis. Recent evidence from large databases reveals possible gender-based
differences in outcomes of carotid artery stenting versus CEA. In this review, we
evaluated clinical articles from 1991 to 2012, using Pubmed and Web of Science,
which addressed gender and outcomes of carotid artery revascularization
procedures. Our goal was to determine whether gender is associated with adverse
outcomes following carotid artery interventions in patients with carotid artery
disease.
PMID- 24347282
TI - Efficacy, safety, and tolerability of pantoprazole magnesium in the treatment of
reflux symptoms in patients with gastroesophageal reflux disease (GERD): a
prospective, multicenter, post-marketing observational study.
AB - BACKGROUND: To improve proton pump inhibitor effects, pharmacological
modifications have been developed such as the use of enantiomer molecules (e.g.,
S-omeprazole, S-pantoprazole, or dexlansoprazole), or addition of NaHCO3 (for an
immediate release) or magnesium (with a lower absorption for a more sustained
effect). OBJECTIVE: The objective of this study was to assess the efficacy,
safety, and tolerability of pantoprazole magnesium 40 mg once daily for 4 weeks,
on the relief of reflux symptoms in gastroesophageal reflux disease (GERD)
patients. METHODS: A phase IV, open-label, prospective, multicenter study was
designed. Patients included were prescribed pantoprazole magnesium 40 mg orally
once daily for 28+/-2 days. All patients had a history of persistent or recurrent
heartburn and/or acid regurgitation for at least 3 months. Effectiveness and
tolerability data obtained from patients who completed a minimum of 4 weeks of
pantoprazole magnesium treatment were considered for analysis. RESULTS: The
account of baseline characteristics and demographics of GERD symptom intensity
was made by analyzing the group of 4,343 patients that fulfilled all inclusion
criteria; 54% were females (n=2,345) and 46% (n=1,998) males, with a mean age of
36.2+/-7.5 years. Severity of symptoms, assessed by the physician using the 4
point Likert scale, reduced by at least 80% from baseline intensity after
treatment in the per protocol population. In the case of the intention-to-treat
population, the improvement in symptom intensity was 73%. The number of patients
that experienced any adverse events was 175/5,027 (3.48%). CONCLUSIONS:
Pantoprazole magnesium is a safe, effective, and well-tolerated drug that
significantly improves GERD symptoms.
PMID- 24347283
TI - Three-dimensional structure of a sugar N-formyltransferase from Francisella
tularensis.
AB - N-formylated sugars have been observed on the O-antigens of such pathogenic Gram
negative bacteria as Campylobacter jejuni and Francisella tularensis. Until
recently, however, little was known regarding the overall molecular architectures
of the N-formyltransferases that are required for the biosynthesis of these
unusual sugars. Here we demonstrate that the protein encoded by the wbtj gene
from F. tularensis is an N-formyltransferase that functions on dTDP-4-amino-4,6
dideoxy-d-glucose as its substrate. The enzyme, hereafter referred to as WbtJ,
demonstrates a strict requirement for N(10) -formyltetrahydrofolate as its carbon
source. In addition to the kinetic analysis, the three-dimensional structure of
the enzyme was solved in the presence of dTDP-sugar ligands to a nominal
resolution of 2.1 A. Each subunit of the dimeric enzyme is dominated by a "core"
domain defined by Met 1 to Ser 185. This core motif harbors the active site
residues. Following the core domain, the last 56 residues fold into two alpha
helices and a beta-hairpin motif. The hairpin motif is responsible primarily for
the subunit:subunit interface, which is characterized by a rather hydrophobic
pocket. From the study presented here, it is now known that WbtJ functions on C
4' amino sugars. Another enzyme recently investigated in the laboratory, WlaRD,
formylates only C-3' amino sugars. Strikingly, the quaternary structures of WbtJ
and WlaRD are remarkably different. In addition, there are several significant
variations in the side chains that line their active site pockets, which may be
important for substrate specificity. Details concerning the kinetic and
structural properties of WbtJ are presented.
PMID- 24347284
TI - PIK3CA gene alterations in bladder cancer are frequent and associate with reduced
recurrence in non-muscle invasive tumors.
AB - Bladder cancer (BC) is the fifth most common cancer in the world, being the non
muscle invasive tumors (NMIBC) the most frequent. NMIBC shows a very high
frequency of recurrence and, in certain cases, tumor progression. The
phosphatidylinositol 3-kinase (PI3K) pathway, which controls cell growth,
tumorigenesis, cell invasion and drug response, is frequently activated in
numerous human cancers, including BC, in part through alterations of PIK3CA gene.
However, the significance of PIK3CA gene alterations with respect to
clinicopathological characteristics, and in particular tumor recurrence and
progression, remains elusive. Here, we analyzed the presence of mutations in
FGFR3 and PIK3CA genes and copy number alterations of PIK3CA gene in bladder
tumor and their correspondent paired normal samples from 87 patients. We observed
an extremely high frequency of PIK3CA gene alterations (mutations, copy gains, or
both) in tumor samples, affecting primarily T1 and T2 tumors. A significant
number of normal tissues also showed mutations and copy gains, being coincident
with those found in the corresponding tumor sample. In low-grade tumors PIK3CA
mutations associated with FGFR3 mutations. Alterations in PIK3CA gene resulted in
increased Akt activity in tumors. Interestingly, the presence of PIK3CA gene
alterations, and in particular gene mutations, is significantly associated with
reduced recurrence of NMIBC patients. Importantly, the presence of FGFR3
mutations may influence the clinical outcome of patients bearing alterations in
PIK3CA gene, and increased recurrence was associated to FGFR3 mutated, PIK3CA wt
tumors. These findings may have high relevance in terms of using PI3K-targeted
therapies for BC treatment.
PMID- 24347285
TI - Corticosteroids may favor proliferation of thoracic inflammatory myofibroblastic
tumors.
AB - Inflammatory myofibroblastic tumor (IMT) was thought to represent a benign post
infectious or post-inflammatory process cured by surgical resection. However,
reports of cases with an aggressive clinical course suggest the need for caution
about the prognosis. The treatment of choice is a complete surgical resection,
while medical treatment options are limited. Corticosteroid therapy has been used
with some success in unresectable lesion. However, rapid progression of lung IMT
after prednisone treatment has been reported, raising the hypothesis that
corticosteroids may favor a tumultuous proliferation of this lesion, possibly
through immunosuppression. We here report a similar observation and suggest that
other mechanisms may be involved. A 5-year and 6-month-old boy presented with a
72 hr history of breathlessness, initially responsive to albuterol and
prednisone. He represented 15 days later with increasing symptoms despite further
prednisone treatment. CT chest scan showed a mass lesion in the tracheal lumen,
which on biopsy was found to be an IMT. The possibility that prednisone may have
an enhancing effect on IMT cell proliferation is demonstrated through IMT cell
culture and discussed.
PMID- 24347286
TI - MR and CEUS monitoring of patients with severe rheumatoid arthritis treated with
biological agents: a preliminary study.
AB - PURPOSE: This study was done to propose a study protocol for patients with
rheumatoid arthritis (RA) treated with biological agents, by evaluating the
contribution of contrast-enhanced magnetic resonance (CE-MR) imaging, a software
programme that calculates the volume of synovitis on CE-MR images, and contrast
enhanced ultrasound (CEUS). MATERIALS AND METHODS: Sixteen patients with RA
receiving treatment with biologics were analysed. The patients underwent clinical
examination, CE-MR imaging and CEUS on the same day. Images were postprocessed
with the software and evaluated independently by three physicians in terms of
RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score), SAMIS (Simplified
Rheumatoid Arthritis Magnetic Resonance Imaging Score) and CEUS grade. The
techniques were correlated statistically. RESULTS: The RAMRIS and SAMIS scores
were found to correlate statistically. CE-MR imaging correlated with the clinical
data (p < 0.05), whereas CEUS did not. The data provided by the software did not
correlate statistically with the other techniques. The most painful joint was
consistently found to be the joint with most synovitis. CONCLUSIONS: CE-MR
imaging may be used prior to treatment and for long-term follow-up. CEUS might be
useful in the short-term follow-up, as it seems to provide an indication of the
presence or absence of disease, though not of its severity. The software is a
very useful tool that can supplement, but not replace, the other techniques.
PMID- 24347287
TI - Activation of a positive feedback loop involving IL-6 and aromatase promotes
intratumoral 17beta-estradiol biosynthesis in endometrial carcinoma
microenvironment.
AB - Tumor-stroma interactions contribute greatly to intratumoral estrogen
biosynthesis in endometrial carcinoma, but the mechanisms involved remain largely
unknown. Previous study demonstrated that intratumoral aromatase upregulation in
stromal cells participated in this process, but the specific aromatase-regulators
have not been reported. In the present study, we found that aromatase expression
in intratumoral stroma, but not in tumor epithelium, correlated positively with
interleukin 6 (IL-6) expression in cancer epithelial cells by
immunohistochemistry, which was confirmed using laser capture
microdissection/real-time reverse transcription-PCR. With stimulation by
exogenous IL-6, aromarase expression was increased in stromal cells not but not
in cancer cells. Aromatase mRNA levels in endometrial cancer cells were not
influenced by cocultivation with intratumoral stromal cells. When cocultured with
17beta-estradiol (E2 )-treated cancer cells, aromatase mRNA in stromal cells was
significantly elevated and increased IL-6 protein levels were detected in E2
treated culture medium. Next, we demonstrated that E2 -induced IL-6 production
was through cooperation between estrogen receptor alpha and nuclear factor-kappa
B. Furthermore, an IL-6 receptor blocking antibody could attenuate the
upregulation of aromatase expression in stromal cells and the E2 concentration in
coculture systems of cancer and stromal cells. The results were confirmed by an
orthotopic nude endometrial carcinoma model in vivo. These studies elucidated the
activation of a positive feedback loop, that is, IL-6 stimulated by E2 in
endometrial cancer cells induced aromatase expression in stromal cells, promoting
enhanced intratumoral E2 synthesis. Blocking of this tumor-stroma interaction may
be a therapeutic strategy to overcome in situ estrogen biosynthesis in
endometrial carcinoma.
PMID- 24347288
TI - Total colonic aganglionosis: a 15-year single center experience.
AB - PURPOSE: Total colonic aganglionosis (TCA) is a rare condition, which is
challenging to manage. Outcome data are sparse. We aimed to review the
demographics, treatment, and outcomes of TCA in our center. PATIENTS AND METHODS:
A retrospective case note review of 15 years from a single center was undertaken.
RESULTS: A total of nine patients (five male) were managed. Gestational age at
birth was 39 weeks (range, 32.5-41 weeks). All patients were referred with distal
intestinal obstruction at a median of day 2 (range, 1-6 days) of life. Two
patients were managed with a long-term stoma. One died with persistent functional
obstruction (despite a ganglionic stoma). Of the nine patients, seven patients
underwent staged pull-through: three Soave, three Duhamel, and one Martin
procedure with no short-term complications. All patients had at least one
readmission with enterocolitis, diarrhea, or high stoma output. Further
procedures were required in four of the seven patients. Only one child (older
than 3 years) has achieved continence. Two children (both aged 8 years) requested
reformation of a stoma to manage incontinence. CONCLUSION: In this series, we
observed high morbidity and poor functional outcome, which should be anticipated
in TCA. Patients with TCA have a high probability of requiring a long-term stoma
and this should be considered as a management option.
PMID- 24347289
TI - Para-axillary subcutaneous endoscopic approach in torticollis: tips and tricks in
the surgical technique.
AB - AIM: An obvious scar on the neck may appear following the open surgery for
congenital muscular torticollis (CMT). The cosmetic result may displease the
patient and the family. In this study, we describe a minimally invasive
technique, para-axillary subcutaneous endoscopic approach (PASEA) in CMT.
PATIENTS AND METHODS: A total of 11 children (seven girls and four boys with the
age range between 1 and 15 years) were operated for torticollis by PASEA. All
patients had facial asymmetry and head and neck postural abnormality. Following
an incision at the ipsilateral para-axillary region, a subcutaneous cavernous
working space is formed toward sternocleidomastoid (SCM) muscle. The muscle and
fascia are cut by cautery under endoscopic vision. The patients had postoperative
2nd-week and 3rd-month visits. The incision scar, inspection, and palpation
findings of the region, head posture, and shoulder position of the affected side
were considered in evaluation of the cosmetic outcome. Preoperative and
postoperative range of motion of the head and neck were compared for functional
outcome. RESULTS: We preferred single incision surgery in our last two patients;
the rest had double para-axillary incision for port insertion. Incomplete
transection of the muscle was not observed. There was no serious complication.
Postoperatively, head posture and shoulder elevation were corrected
significantly. Range of motion of the head was improved. Postoperatively, all the
patients had rotation capacity with more than 30 degrees. The range of
postoperative flexion and extension movements was between 45 and 60 degrees.
CONCLUSIONS: The open surgery techniques of CMT causes visible lifelong incision
scar on the neck. PASEA leaves a cosmetically hidden scar in the axillary region.
A single incision surgery is also possible. A well-formed cavernous working space
is needed. External manual palpation, delicate dissection, and cutting of SCM
muscle with cautery are the important components of the procedure. Surgeons
having experience in pediatric minimal invasive surgery may consider PASEA as an
alternative to the open approach in CMT. The surgeon should be familiar with
surgical anatomy of the neck and must be highly competent in management of
possible complications in the region.
PMID- 24347290
TI - In vivo waveguide elastography: effects of neurodegeneration in patients with
amyotrophic lateral sclerosis.
AB - PURPOSE: Waveguide elastography (WGE) combines magnetic resonance elastography
(MRE), diffusion tensor imaging (DTI), and anisotropic inversions for a
determination of the elastic properties of white matter. Previously, the method
evaluated the anisotropic elastic properties of the corticospinal tracts (CSTs)
of healthy volunteers. Here, the sensitivity of WGE is tested for the detection
of pathologic changes in a cohort of patients with Amyotrophic Lateral Sclerosis
(ALS). METHODS: MRE and DTI were performed in 14 patients with ALS and 14
healthy, age-matched controls. A comparison was made between three components
from WGE and the DTI metrics FA, MD, PD, and RD, for the detection of differences
between patients and controls. It was hypothesized that the stiffness values in
the CSTs of the patients would be significantly lower due to the known
neurodegeneration associated with ALS. RESULTS: Two anisotropic shear moduli
polarized parallel and perpendicular to the CSTs were significantly reduced in
ALS patients (P < 0.0001), whereas the anisotropic longitudinal modulus polarized
parallel to the CSTs showed no significant differences. CONCLUSION: The results
of this study suggest a relatively high sensitivity of two anisotropic shear
moduli as noninvasive metrics for the assessment of neuronal degeneration within
the CSTs.
PMID- 24347291
TI - A survey of aflatoxins in sesame seeds imported into Khorasan Province, Iran.
AB - Sesame seed is one of the main nutrient substances which is used in the food
industries of Khorasan Razavi, Iran. Because it is likely that stored sesame
seeds are contaminated with mycotoxins, the levels of aflatoxins (AF) in five
lots of imported sesame seeds before their distribution to the market were
studied during one year. A total of 269 sub-samples were obtained from a total of
9,321 tons of sesame seeds from five importing companies. Aflatoxins at >1 MUg/kg
were found in 50 % of all samples, but at low levels in most cases, which is
illustrated by mean AFB1 and total AF levels of 1.25 +/- 3.70 and 1.43 +/- 4.38
MUg/kg, respectively. A few (1.9 %) samples exceeded the National Iranian
Standard maximum accepted level for AFB1 (5 MUg/kg) or total AF (15 MUg/kg); the
maximum total AF level found in one sample was 48 MUg/kg. The results indicate
that the risk of a violative AF contamination in imported sesame seeds is not
negligible but is currently relatively low.
PMID- 24347292
TI - Texture-based classification of liver fibrosis using MRI.
AB - PURPOSE: To investigate the ability of texture analysis of MRI images to stage
liver fibrosis. Current noninvasive approaches for detecting liver fibrosis have
limitations and cannot yet routinely replace biopsy for diagnosing significant
fibrosis. MATERIALS AND METHODS: Forty-nine patients with a range of liver
diseases and biopsy-confirmed fibrosis were enrolled in the study. For texture
analysis all patients were scanned with a T2 -weighted, high-resolution, spin
echo sequence and Haralick texture features applied. The area under the receiver
operating characteristics curve (AUROC) was used to assess the diagnostic
performance of the texture analysis. RESULTS: The best mean AUROC achieved for
separating mild from severe fibrosis was 0.81. The inclusion of age, liver fat
and liver R2 variables into the generalized linear model improved AUROC values
for all comparisons, with the F0 versus F1-4 comparison the highest (0.91).
CONCLUSION: Our results suggest that a combination of MRI measures, that include
selected texture features from T2 -weighted images, may be a useful tool for
excluding fibrosis in patients with liver disease. However, texture analysis of
MRI performs only modestly when applied to the classification of patients in the
mild and intermediate fibrosis stages.
PMID- 24347293
TI - Artificial leaf goes simpler and more efficient for solar fuel generation.
AB - Layer upon layer: Solar-to-fuel conversion through water splitting is among the
most challenging and growing fields in present day science. Herein, a report is
highlighted that successfully demonstrates an efficient photoanodic system
utilizing simple and low-cost tungsten-doped bismuth vanadate on single- or
double-junction amorphous silicon photovoltaic in a tandem configuration.
PMID- 24347294
TI - Ferritin trends do not predict changes in total body iron in patients with
transfusional iron overload.
AB - Ferritin levels and trends are widely used to manage iron overload and assess the
efficacy of prescribed iron chelation in patients with transfusional iron
loading. A retrospective cohort study was conducted in 134 patients with
transfusion-dependent anemia, over a period of up to 9 years. To determine
whether the trends in ferritin adequately reflect the changes in total body iron,
changes in ferritin between consecutive liver iron measurements by magnetic
resonance imaging (MRI) were compared to changes in liver iron concentrations
(LIC), a measure of total body iron. The time period between two consecutive LIC
measurements was defined as a segment. Trends in ferritin were considered to
predict the change in LIC within a segment if the change in one parameter was
less than twofold that of the other, and was in the same direction. Using the
exclusion criteria detailed in methods, the trends in ferritin were compared to
changes in LIC in 358 segments. An agreement between ferritin trends and LIC
changes was found in only 38% of the 358 segments examined. Furthermore, the
change in ferritin was in opposite direction to that of LIC in 26% of the
segments. Trends in ferritin were a worse predictor of changes in LIC in sickle
cell disease than in thalassemia (P < 0.01). While ferritin is a convenient
measure of iron status; ferritin trends were unable to predict changes in LIC in
individual patients. Ferritin trends need to be interpreted with caution and
confirmed by direct measurement of LIC.
PMID- 24347295
TI - Horizontal comparative fluorescence two-dimensional gel electrophoresis for
improved spot coordinate detection.
AB - Vertical comparative 2D fluorescence gel electrophoresis (CoFGE) has recently
been shown to increase the reproducibility of coordinate assignment for protein
spots, in particular in singular experiments, which cannot be investigated using
DIGE. The method applies a standardized marker grid formed by a set of purified
proteins to the sample proteome in a conglomerate of 1DE, 2DE, and DIGE. Here,
improvements are demonstrated by transferring CoFGE to horizontal 2DE. These
include the elimination of the protein modification by residual acrylamide
monomer unavoidable in vertical CoFGE, reduced buffer volumes, and highly
efficient laboratory procedures. Spot patterns are well defined and can be easily
analyzed using commercially available warping algorithms. With horizontal CoFGE
also a correction for changes in pI was introduced using a third fluorescent dye.
Horizontal CoFGE holds high promises in comparative proteomics.
PMID- 24347296
TI - Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and
anticancer bone reconstruction.
AB - The progress in bone cancer surgery and multimodal treatment concept achieve only
modest improvement in the overall survival, due to failure in clearing out
residual cancer cells at the surgical margin and extreme side-effects of adjuvant
postoperative treatments. Our study aims to propose a new method based on
cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a
high local drug concentration with a sustained release profile and a better
control of residual malignant cells via local drug delivery and promotion of the
reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic
molecules, can be incorporated into HA (bone regeneration scaffold) through
thermal treatment. The parameters of polyCD treatment on the macroporous HA
(porosity 65%) were characterized via thermogravimetric analysis. Good
cytocompatibility of polyCD functionalized bioceramics was demonstrated on
osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an
anticancer agent (cisplatin) were respectively loaded on polyCD functionalized
bioceramics for drug release test. The results show that polyCD functionalization
leads to significantly improved drug loading quantity (30% more concerning
gentamicin and twice more for cisplatin) and drug release duration (7 days longer
concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study
offers a safe and reliable drug delivery system for bioceramic matrices, which
can load anticancer agents (or/and antibiotics) to reduce local recurrence
(or/and infection).
PMID- 24347297
TI - Genetic variability and geographic typicality of Italian former Prosecco grape
variety using PCR-derived molecular markers.
AB - This study uses PCR-derived marker systems to investigate the extent and
distribution of genetic variability of 80 Italian Prosecco accessions coming from
Prosecco DOC area (north-east area of Italy). The studied samples include
genotypes from Veneto and Friuli Venezia Giulia region. In order to verify the
varietal identity of the samples, analyses based on 22 SSR loci were performed,
and two grape varieties were found: Prosecco tondo and Prosecco lungo. In
addition to microsatellite analysis, intra-varietal variability study was
performed using AFLP, SAMPL, ISSR, and M-AFLP molecular markers. This molecular
approach could discriminate different Prosecco tondo accessions coming from
Treviso hills, from Veneto plain, from Friuli Venezia Giulia region, and from
Padua hills (Serprina samples). As concerning Prosecco lungo variety, it was
possible to discriminate molecularly the accessions from Veneto region and those
from Friuli Venezia Giulia region. The molecular analysis allowed a distinction
of the Prosecco genotypes on the basis of their geographic origins with plant
specific markers able to differentiate all Prosecco accessions. In this paper,
the studied grape variety is termed Prosecco and not Glera (which is the present
name) because the sampled vineyards were established many years ago when the name
of the variety was Prosecco.
PMID- 24347298
TI - Getting stung by black scorpion Androctonus crassicauda: a case report.
AB - Importance of the correct diagnosis in the correct early management of a scorpion
stung patient by using antivenom is not emphasized, particularly when there are
little evidences. A 65-year-old female was brought to our emergency department
with the chief compliant of being stung by an unknown object 3 h earlier while
traveling in an intercity bus. She became agitated and simultaneously experienced
tachycardia, very severe generalized sweating, cold and wet extremities,
bilateral diffuse crackle in the base of lungs, tachypnea, and lethargy. With the
primitive diagnosis of myocardial infarction, scorpion sting was documented as
the cause of this combined cholinergic and adrenergic syndrome after the scorpion
was found in the patient's bed clothes. She dramatically responded to the
administration of low dose of scorpion antivenom. This case dramatically
responded to the antivenom administration, especially the cholinergic and
sympathetic signs, pulmonary edema, and electrocardiographic changes were fully
and almost immediately recovered. Scorpion antivenom may reverse life-threatening
manifestations of scorpion envenomation if used early and in appropriate
patients.
PMID- 24347299
TI - Environmental toxins: alarming impacts of pesticides on male fertility.
AB - This review comprehensively summarizes the effects of more than 15 mostly used
pesticides on male reproductive physiology, as recent experimental and
epidemiological research have indicated their alarming impact on overall human
health. Mechanisms have described that pesticide exposure damages spermatozoa,
alter Sertoli or Leydig cell function, both in vitro and in vivo and thus affects
semen quality. But, the literature suggests a need for more intricate research in
those pesticides that are defined as mutagens or carcinogens and directly affect
the hypothalamic-pituitary-gonadal axis. This literature review also proposes
specific solutions to overcome these health effects.
PMID- 24347300
TI - Vasorelaxant effects of mercury on rat thoracic aorta: the nitric oxide signaling
mechanism.
AB - Mercury, a heavy metal, is widespread and persistent in the environment and has
been elucidated as a possible risk factor in cardiovascular diseases. Mercury has
been reported to selectively impair the nitric oxide (NO) pathway in the vascular
endothelium as a consequence of oxidative stress. Conversely, mercury per se
causes endothelium-dependent vasorelaxation at lower concentration via the NO
pathway. Little is known about the effects of mercury per se on other endothelial
mediators. To elucidate possible mechanisms involved in this action, isometric
tension was measured in aortic rings precontracted with phenylephrine (10 uM)
from Wistar rats. Responses to increasing concentrations of inorganic mercuric
chloride (10(-12)-10(-5) M) were obtained in the presence and absence of
endothelium. Inorganic mercury produced a biphasic response in endothelium-intact
aortic rings and produced only vasoconstriction in endothelium-denuded aortic
rings. To study the possible underlying mechanisms for the biphasic response of
mercury, increasing concentrations of mercuric chloride (10(-12)-10(-5) M) were
used before and after N(G)-nitro-L-arginine methyl ester (L-NAME (10(-4) M)),
glybenclamide (10(-5) M), superoxide dismutase (10 U/ml) + catalase (100 U/ml),
and nifedipine (10(-4) M) treatment. Results suggest that mercury produces
endothelium-dependent relaxation at low concentration mediated by endothelial
generated NO and endothelium-derived hyperpolarizing factor and endothelium
independent contraction resulting from the blockade of L-type Ca(2+) channels by
generation of free radicals.
PMID- 24347301
TI - Mitochondrial dysfunction and respiratory chain defects in a rodent model of
methotrexate-induced enteritis.
AB - The efficacy of methotrexate (MTX), a widely used chemotherapeutic drug, is
limited by its gastrointestinal toxicity and the mechanism of which is not clear.
The present study investigates the possible role of mitochondrial damage in MTX
induced enteritis. Small intestinal injury was induced in Wistar rats by the
administration of 7 mg kg(-1) body wt. MTX intraperitoneally for 3 consecutive
days. MTX administration resulted in severe small intestinal injury and extensive
damage to enterocyte mitochondria. Respiratory control ratio, the single most
useful and reliable test of mitochondrial function, and 3-(4,5-dimethylthiazol-2
yll)-2,5-diphenyltetrazolium bromide reduction, a measure of cell viability were
significantly reduced in all the fractions of MTX-treated rat enterocytes. A
massive decrease (nearly 70%) in the activities of complexes II and IV was also
observed. The results of the present study suggest that MTX-induced damage to
enterocyte mitochondria may play a critical role in enteritis. MTX-induced
alteration in mitochondrial structure may cause its dysfunction and decreases the
activities of the electron chain complexes. MTX-induced mitochondrial damage can
result in reduced adenosine triphosphate synthesis, thereby interfering with
nutrient absorption and enterocyte renewal. This derangement may contribute to
malabsorption of nutrients, diarrhea, and weight loss seen in patients on MTX
chemotherapy.
PMID- 24347302
TI - Modulatory effects of L-carnitine on tamoxifen toxicity and oncolytic activity:
in vivo study.
AB - The aim of this study was to investigate the protective effect of L-carnitine (L
CAR) in tamoxifen (TAM)-induced toxicity and antitumor activity. Adult female
rats were randomly divided into four groups. Group I was served as control,
groups II and III were treated with TAM (10 mg/kg, periorally) and L-CAR (300
mg/kg, intraperitoneally), respectively, while group IV was treated with both
compounds. The treatment continued daily for 28 days. Administration of TAM
resulted in significant increase in serum lipid profiles, liver enzymes, and
bilirubin level. TAM produced a significant increase in lipid peroxides (LPO)
level and nonsignificant change in nitrogen oxide (NO(x)) level accompanied with
significant decrease in superoxide dismutase (SOD) activity of hepatic and uterus
tissues and significant decrease in glutathione (GSH) content of uterus tissue.
Administration of L-CAR for 1 h prior to TAM treatment decreased serum lipids and
liver enzymes significantly and significantly increased SOD activity in liver and
uterus tissues compared with TAM-treated group. Furthermore, it restored LPO and
GSH levels and increased NO(x) level in uterus tissue. DNA fragmentation and the
apoptotic marker, caspase-3, were not detected in the liver of all treated
groups. Histopathologically, alterations in the liver and uterus structures after
TAM treatment, which was attenuated after L-CAR administration. The antitumor
effect and survival of the combined treatment of Ehrlich ascites carcinoma (EAC)
bearing mice was less than each one alone. L-CAR interestingly increased survival
rate of EAC-bearing mice more than TAM-treated group. In conclusion, L-CAR has
beneficial effects regarding TAM toxicity; however, it interferes with its
antitumor effect.
PMID- 24347303
TI - The HBM domain: introducing bimodularity to bacterial sensing.
AB - We have recently reported the three dimensional structure of the McpS
chemoreceptor sensor domain in complex with its cognate ligands. The domain was
characterized by a bimodular architecture, where ligand binding to each module
caused a chemotactic response. This is a novel small molecule binding domain,
which, however, is un-annotated in relevant databases. We report here the domain
signature of the family of McpS-like sensor domains, which was termed helical
bimodular (HBM) domain. The HBM domain was identified in Bacteria and Archaea and
forms part of chemoreceptors and histidine kinases. The conservation of amino
acids in the ligand binding sites of both modules suggests that HBM family
members recognize similar ligands.
PMID- 24347304
TI - [Public health services origins from the Nazi past].
PMID- 24347306
TI - Investigating the quantitative fidelity of prospectively undersampled chemical
shift imaging in muscular dystrophy with compressed sensing and parallel imaging
reconstruction.
AB - PURPOSE: Fat fraction measurement in muscular dystrophy has an important role to
play in future therapy trials. Undersampled data acquisition reconstructed by
combined compressed sensing and parallel imaging (CS-PI) can potentially reduce
trial cost and improve compliance. These benefits are only gained from
prospectively undersampled acquisitions. METHODS: Eight patients with Becker
muscular dystrophy were recruited and prospectively undersampled data at ratios
of 3.65*, 4.94*, and 6.42* were acquired in addition to fully sampled data:
equivalent coherent undersamplings were acquired for reconstruction with parallel
imaging alone (PI). Fat fraction maps and maps of total signal were created using
a combined compressed sensing/parallel imaging (CS-PI) reconstruction. RESULTS:
The CS-PI reconstructions are of sufficient quality to allow muscle delineation
at 3.65* and 4.94* undersampling but some muscles were obscured at 6.42*. When
plotted against the fat fractions derived from fully sampled data, non
significant bias and 95% limits of agreement of 1.58%, 2.17% and 2.41% were found
for the three CS-PI reconstructions, while a 3.36* PI reconstruction yields
2.78%, 1.8 times worse than the equivalent CS-PI reconstruction. CONCLUSION:
Prospective undersampling and CS-PI reconstruction of muscle fat fraction mapping
can be used to accelerate muscle fat fraction measurement in muscular dystrophy.
PMID- 24347307
TI - Raising-flap technique for outflow reconstruction in living donor liver
transplantation.
PMID- 24347308
TI - Outcomes of the Evidence-Based Pitocin Administration Checklist at a Tertiary
Level Hospital.
AB - Pitocin, a synthetic form of the hormone oxytocin, is a high-alert medication
that heightens patient harm when used incorrectly. This investigation examined
the outcomes of an evidence-based Pitocin administration checklist used for labor
augmentation at a tertiary-level hospital. Data came from patient records. Using
the Perinatal Trigger Tool, N = 372 clinical records (n = 194 prior to and n =
178 following checklist implementation) were reviewed. Checklist implementation
resulted in statistically significant reductions in the duration of
hospitalization (1.72 vs. 2.02 days, p = .0005), presence of meconium (23.7% vs.
6.7%, p < .001), maternal fevers (7.2% vs. 2.3%, p = .030), and episiotomies
(8.8% vs. 1.7%, p = .002), and clinically important reduction in APGAR scores < 7
at 5 min (3.6%-0.6%, p = .069) and instrumented deliveries (11.9%-8.4%, p =
.307). A universal Pitocin checklist implementation can improve birth outcomes
and costs of care.
PMID- 24347309
TI - Identification of the PKR nuclear interactome reveals roles in ribosome
biogenesis, mRNA processing and cell division.
AB - The double-strand RNA-dependent protein kinase, PKR, plays a central role in
inflammatory/chronic stress-mediated pathologies such as cancer, diabetes, and
neuro/muscular degenerative diseases. Although a significant amount of research
has been conducted to elucidate the role of PKR signaling in the cytosol, only
recently has attention been paid to the role of PKR in the nuclear compartment.
Previously our group reported that phosphorylated forms of PKR are present in the
nucleus of acute leukemic cell lines, representing a reservoir of active kinase
that responds to stress. Using the CCRF-CEM acute T-cell leukemia cell line, a
PKR-specific inhibitor, co-immunoprecipitation and a proteomics approach, which
included affinity purified mass spectrometry analysis (AP/MS), we identified the
proteins present in active and inactive PKR nuclear complexes. Of the proteins
identified in the PKR complexes, sixty-nine (69) were specific to the active
complex, while thirty-eight (38) were specific to the inactive complex. An
additional thirteen (13) proteins associated specifically with both complexes.
The majority of the proteins identified are involved in, ribosome biogenesis, RNA
splicing, mRNA stability, gene expression, cell cycle, or chromatin organization,
including several with known significance to normal hematopoiesis and/or
hematological disease. In agreement with the AP/MS data, basal- or over
expression of PKR under normal growth conditions favored cell proliferation in
the tested cell lines, whereas pharmacological inhibition of PKR or shRNA
mediated knock-down did not. PKR was also found to influence the isoform and the
level of expression of the proto-oncogene MYC.
PMID- 24347311
TI - Sternocleidomastoid muscle additionally innervated by the facial nerve: case
report and review of the literature.
AB - An aberrant nerve branch from the facial nerve, additionally to the accessory
nerve and cervical rami C2 and C3, was observed innervating the
sternocleidomastoid (SCM) muscle in a 75-year-old male cadaver. We consider that
the anomaly occurred as the result of a fusion of the muscular compartment from
the digastric and SCM muscles during development. The aberrant innervation may be
the source of the misinterpretation of electromyographic findings.
PMID- 24347310
TI - Changes in MR relaxation times of the meniscus with acute loading: an in vivo
pilot study in knee osteoarthritis.
AB - PURPOSE: To prospectively evaluate changes in T1rho and T2 relaxation times in
the meniscal body with acute loading using MRI in osteoarthritic knees and to
compare these findings with those of age-matched healthy controls. MATERIALS AND
METHODS: Female subjects above 40 years of age with (N1 = 20) and without
osteoarthritis (OA) (N2 = 10) were imaged on a 3 Tesla MR scanner using a custom
made loading device. MR images were acquired, with the knee flexed at 20 degrees
, with and without a compressive load of 50% of the subject's bodyweight. The
subjects were categorized based on the radiographic evidence of OA. Three
different zones (outer, middle, and inner) of meniscus body were defined (each
occupying 1/3rd the width). After adjusting for age and body mass index in the
general linear regression model, repeated measures analysis of variance was used
to detect significant differences in T1rho and T2 with and without loading.
RESULTS: In the unloaded condition, the average T1rho and T2 times were elevated
in the outer and middle zones of the medial meniscus in OA subjects compared with
the controls. In the loaded condition, T1rho and T2 times of the outer zone of
the medial meniscus was significantly elevated in OA subjects compared with
controls. Finally the change (from unloaded to loaded) was significantly higher
in controls than OA subjects (15.1% versus 8.3%; P = 0.039 for DeltaT1rho , and
11.5% versus 6.9%, P = 0.049 for DeltaT2 ). CONCLUSION: These findings suggest
that while the OA process appears to affect the relaxation times of all regions
within the meniscus, it may affect some regions sooner or to a greater degree.
Furthermore, the differences in the change in relaxation times between unloaded
and loaded conditions may reveal evidence about load transmission failure of the
outer zone of the medial meniscus in subjects with knee OA. It is possible that
these metrics (DeltaT1rho and DeltaT2 ) may be valuable as an early biomechanical
biomarker, which could be used to predict load transmission to the underlying
articular cartilage.
PMID- 24347312
TI - Single-incision laparoscopic common bile duct exploration with conventional
instruments: an innovative technique and a comparative study.
AB - BACKGROUND: Single-incision laparoscopic surgery developed rapidly in recent
years. We introduce an innovative technique: single-incision laparoscopic common
bile duct exploration (SILCBDE) with conventional instruments. A retrospective
comparison between SILCBDE and standard laparoscopic common bile duct exploration
(LCBDE) was analyzed. METHODS: Thirty-four patients who underwent LCBDE for
choledocholithiasis in a period of 17 months were enrolled. Seventeen standard
LCBDEs and 17 SILCBDEs were attempted. Simultaneous cholecystectomies were
performed. RESULTS: The stone clearance rate was 94.1% (16 patients) in the
standard LCBDE group and 100% in the SILCBDE group. There was no statistical
difference in demographic distribution, clinical presentations, and operative
results between the two groups, except the SILCBDE group had a higher rate of
acute cholecystitis than the standard LCBDE group (76.5 vs. 35.3%; p < 0.05). One
procedure (5.9%) in the SILCBDE group was converted to a four-incision
transcystic LCBDE. The complication rate was 11.8% (two patients) in the standard
LCBDE group and 5.9% (one patient) in the SILCBDE group. The average follow-up
period was 4.2 months. CONCLUSION: SILCBDE is as safe and efficacious as standard
LCBDE in experienced hands. Choledochoscope manipulation and bile duct repair are
the key skills. Long-term follow-up and further prospective randomized trials are
anticipated.
PMID- 24347313
TI - Optimal management of the splenic vein at the time of venous resection for
pancreatic cancer: importance of the inferior mesenteric vein.
AB - BACKGROUND: Resection of the superior mesenteric vein (SMV)-portal vein (PV)
splenic vein (SV) confluence during pancreatectomy for pancreatic cancer requires
management of the SV. DISCUSSION: Simple SV ligation can result in sinistral
portal hypertension if the inferior mesenteric vein (IMV) enters the confluence
and is thereby resected, or if the IMV is insufficient to drain the SV. We
describe herein three patients whose clinical course confirms the importance of
the IMV decompressing the SV to avoid sinistral hypertension.
PMID- 24347314
TI - Extraduodenal papillectomy: a feasible alternative method of total papillectomy.
AB - Rational treatment for neoplasms of the duodenal papilla (NDPs) is still
controversial, especially for early stage lesions. Total papillectomies are
indicated in patients expected to have adenomas, adenocarcinoma in an adenoma, or
mucosal adenocarcinomas with no lymph node metastases. However, the preoperative
pathological evaluation of NDPs is still challenging and often inaccurate, mainly
because of the complicated anatomical structures involved and the possibility of
an adenocarcinoma in an adenoma. Herein, we introduce a new method of total
papillectomy, the extraduodenal papillectomy (ExDP). In this method, papillectomy
is undertaken from outside of the duodenum, instead of resection from the inside
through a wide incision of the duodenal wall as is done in conventional
transduodenal papillectomy (TDP). The advantages of ExDP are precise and deeper
cutting of the sphincter and shorter exploration time of the tumor compared to
conventional TDP. We demonstrate three representative patients, all of whom had
an uneventful postoperative course. One of them subsequently underwent a pylorus
preserving pancreatoduodenectomy after detailed postoperative pathological
evaluation. Including that patient, no recurrence has occurred with 37-46 months
of follow-up. In conclusion, ExDP is regarded as a "total biopsy" for early stage
borderline lesions and a feasible, less demanding alternative method for the
treatment of NDPs.
PMID- 24347315
TI - Azurophilic granules in myeloma cells.
PMID- 24347316
TI - Antihypertensive treatment and risk of atrial fibrillation: a nationwide study.
AB - AIMS: To examine the associations between antihypertensive treatment with
angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers
(ARBs), beta-blockers, diuretics, or calcium-antagonists, and risk of atrial
fibrillation. We examined these associations using the entire Danish population
from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial
fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on
beta-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57
646), and ARB monotherapy (n = 20 158). Likewise, individuals on ARB monotherapy
were matched 1:1 with individuals on beta-blocker (n = 20 566), diuretic (n = 20
832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All
were free of atrial fibrillation and of predisposing diseases like heart failure,
ischaemic heart disease, diabetes mellitus, and hyperthyroidism at baseline and
none received any other antihypertensive medication. We studied risk of atrial
fibrillation, and used risk of stroke, influenced by lowering blood pressure
rather than renin-angiotensin system blockade per se, as an indicator of the
importance of blood pressure lowering per se. Hazard ratios of atrial
fibrillation for ACEi and ARB monotherapy were 0.12 (95% CI: 0.10-0.15) and 0.10
(0.07-0.14) compared with beta-blocker, 0.51 (0.44-0.59) and 0.43 (0.32-0.58)
compared with diuretic, and 0.97 (0.81-1.16) and 0.78 (0.56-1.08) compared with
calcium-antagonist monotherapy. Risk of stroke did not differ among the five
antihypertensive medications. CONCLUSION: Use of ACEis and ARBs compared with
beta-blockers and diuretics associates with a reduced risk of atrial
fibrillation, but not stroke, within the limitations of a retrospective study
reporting associations. This suggests that controlling activation of the renin
angiotensin system in addition to controlling blood pressure is associated with a
reduced risk of atrial fibrillation.
PMID- 24347318
TI - The grey zone of truth.
PMID- 24347317
TI - Complications after cardiac implantable electronic device implantations: an
analysis of a complete, nationwide cohort in Denmark.
AB - AIMS: Complications after cardiac implantable electronic device (CIED) treatment,
including permanent pacemakers (PMs), cardiac resynchronization therapy devices
with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter
defibrillators (ICDs), are associated with increased patient morbidity,
healthcare costs, and possibly increased mortality. METHODS AND RESULTS:
Population-based cohort study in all Danish patients who underwent a CIED
procedure from May 2010 to April 2011. Data on complications were gathered on
review of all patient charts while baseline data were obtained from the Danish
Pacemaker and ICD Register. Adjusted risk ratios (aRRs) with 95% confidence
intervals were estimated using binary regression. The study population consisted
of 5918 consecutive patients. A total of 562 patients (9.5%) experienced at least
one complication. The risk of any complication was higher if the patient was a
female (aRR 1.3; 1.1-1.6), underweight (aRR 1.5; 1.1-2.3), implanted in a centre
with an annual volume <750 procedures (0-249 procedures: aRR 1.6; 1.1-2.2, 250
499: aRR 2.0; 1.6-2.7, 500-749: aRR 1.5; 1.2-1.8), received a dual-chamber ICD
(aRR 2.0; 1.4-2.7) or CRT-D (aRR 2.6; 1.9-3.4), underwent system upgrade or lead
revision (aRR 1.3; 1.0-1.7), had an operator with an annual volume <50 procedures
(aRR 1.9; 1.4-2.6), or underwent an emergency, out-of-hours procedure (aRR 1.5;
1.0-2.3). CONCLUSION: CIED complications are more frequent than generally
acknowledged. Both patient- and procedure-related predictors may identify
patients with a particularly high risk of complications. This information should
be taken into account both in individual patient treatment and in the planning of
future organization of CIED treatment.
PMID- 24347319
TI - Excluding a giant coronary aneurysm by implantation of a covered stent.
PMID- 24347320
TI - Determination of nitrophenolic compounds from atmospheric particles using hollow
fiber liquid-phase microextraction and capillary electrophoresis/mass
spectrometry analysis.
AB - A hollow-fiber liquid-phase microextraction method was developed to enrich nine
nitrophenolic compounds from aqueous extracts of atmospheric aerosol particles.
Analysis was performed by CE coupled with ESI MS. The BGE composition was
optimized to a 20 mM ammonium acetate buffer at pH 9.7 containing 15% methanol
v/v. Several extraction parameters (composition of organic liquid membrane, pH of
acceptor phase, salting-out effect, extraction time) were investigated for their
effect on the analyte recoveries. The donor phase consisted of a 1.8 mL sample
solution kept at pH 2 while the acceptor phase was a 15 MUL 100 mM aqueous
ammonia solution. Dihexyl ether served as supported liquid membrane. Low
detection limits in the range of nanomole per liter were achieved. Recoveries of
aqueous standard solutions were found to be between 11 and 90% with enrichment
factors between 10 and 100. Interday and intraday repeatabilities were in an
acceptable range for most compounds (6-15% and 7-10%, respectively) but somewhat
higher for 4-nitrocatechol (59 and 48%) and 2-nitrophenol (17 and 35%). The
developed method was found to be competitive with more established method and was
successfully applied to samples of atmospheric particulate matter from field
experiments.
PMID- 24347321
TI - Porous graphene materials for advanced electrochemical energy storage and
conversion devices.
AB - Combining the advantages from both porous materials and graphene, porous graphene
materials have attracted vast interests due to their large surface areas, unique
porous structures, diversified compositions and excellent electronic
conductivity. These unordinary features enable porous graphene materials to serve
as key components in high-performance electrochemical energy storage and
conversion devices such as lithium ion batteries, supercapacitors, and fuel
cells. This progress report summarizes the typical fabrication methods for porous
graphene materials with micro-, meso-, and macro-porous structures. The structure
property relationships of these materials and their application in advanced
electrochemical devices are also discussed.
PMID- 24347322
TI - IGF-1 intranasal administration rescues Huntington's disease phenotypes in YAC128
mice.
AB - Huntington's disease (HD) is an autosomal dominant disease caused by an expansion
of CAG repeats in the gene encoding for huntingtin. Brain metabolic dysfunction
and altered Akt signaling pathways have been associated with disease progression.
Nevertheless, conflicting results persist regarding the role of insulin-like
growth factor-1 (IGF-1)/Akt pathway in HD. While high plasma levels of IGF-1
correlated with cognitive decline in HD patients, other data showed protective
effects of IGF-1 in HD striatal neurons and R6/2 mice. Thus, in the present
study, we investigated motor phenotype, peripheral and central metabolic profile,
and striatal and cortical signaling pathways in YAC128 mice subjected to
intranasal administration of recombinant human IGF-1 (rhIGF-1) for 2 weeks, in
order to promote IGF-1 delivery to the brain. We show that IGF-1 supplementation
enhances IGF-1 cortical levels and improves motor activity and both peripheral
and central metabolic abnormalities in YAC128 mice. Moreover, decreased Akt
activation in HD mice brain was ameliorated following IGF-1 administration.
Upregulation of Akt following rhIGF-1 treatment occurred concomitantly with
increased phosphorylation of mutant huntingtin on Ser421. These data suggest that
intranasal administration of rhIGF-1 ameliorates HD-associated glucose metabolic
brain abnormalities and mice phenotype.
PMID- 24347324
TI - Effect of erythromycin-doped calcium polyphosphate scaffold composite in a mouse
pouch infection model.
AB - We previously showed that strontium-doped calcium polyphosphate (SCPP) scaffold
with poly(vinyl alcohol) (PVA) coating extended the impregnated erythromycin (EM)
release. In this study, we examined the bactericidal effect of EM-doped SCPP
(SCPP(EM) ) scaffolds with PVA coating in a Staphylococcus aureus (S. aureus)
infected mouse pouch. SCPP scaffolds with or without 5% EM, and SCPP(EM)
scaffolds coated with PVA (with or without 5% EM) were prepared. Scaffolds were
implanted in the pouch of BALB/c mice, followed by inoculation of 1 * 10(3)
colony-forming units of S. aureus. Mice were sacrificed 14 days after surgery.
Pouch tissues and scaffolds were collected for histology, scanning electron
microscopy, and microbiological analysis. In the absence of SCPP scaffolds, the
pouch infection was eliminated by the host immune surveillance. In the presence
of SCPP scaffolds, both the pouch tissues and scaffolds were infected, but
SCPP(EM) scaffolds successfully inhibited bacterial growth. Although PVA coating
of SCPP(EM) scaffolds enhanced bacterial growth, incorporation of EM into PVA
coating inhibited growth. In conclusion, BALB/c mice were capable of eradicating
a low grade S. aureus infection. SCPP protected S. aureus growth from host immune
surveillance. Though PVA coating sustained EM release in vitro, it was unable to
inhibit bacterial growth because PVA gel matrix provided a temporary shelter for
bacteria to grow and slowed the EM release from SCPP scaffold. To guarantee a
sufficient inhibition of bacterial growth at the initial stage, embedding EM or
other antibiotics in the PVA coating is also essential.
PMID- 24347325
TI - Endocrine disruptors differently influence estrogen receptor beta and androgen
receptor in male and female rat VSMC.
AB - Sex steroid hormones differently control the major physiological processes in
male and female organisms. In particular, their effects on vascular smooth muscle
cells (VSMCs) migration are at the root of sex/gender-related differences
reported in the cardiovascular system. Several exogenous substances, defined
endocrine disruptor chemicals (EDCs), could interfere with these androgen and
estrogen effects; however, the sex/gender-related susceptibility of VSMC motility
to EDCs is completely unknown. Here, the effect of naturally occurring
(naringenin, Nar) and synthetic (bisphenol A, BPA) EDCs on male and female VSMC
motility has been evaluated. 17beta-estradiol (E2, 0.1 nM-1 uM) induced a dose
dependent inhibition of motility in female-derived VSMC. In contrast, neither
dihydrotestosterone (DHT, 0.01-100 nM) nor the common precursor of sex steroid
hormones, testosterone (Tes, 0.01-100 nM) modified male-derived VSMC motility.
Estrogen receptor (ER) beta subtype-dependent activation of p38 was necessary for
the E2 effect on cell motility. High BPA concentration prevented E2 effects in
female-derived cells being without any effect in male-derived cells. Nar mimicked
E2 effects on female-derived cells even in the presence of E2 or BPA.
Intriguingly, Nar also inhibited the male-derived VSMC mobility. This latter
effect was prevented by ERbeta inhibitor, but not by the androgen receptor (AR)
inhibitor. As a whole, ERbeta-dependent signals in VSMC results more susceptible
to the impact of EDCs than AR signals suggesting a possible high and overall
susceptibility of female to EDCs. However, several male-derived cells, including
VSMC, express ERbeta, which could also serve as target of EDC disruption in male
organisms.
PMID- 24347327
TI - Four dimensional spectral-spatial fat saturation pulse design.
AB - PURPOSE: The conventional spectrally selective fat saturation pulse may perform
poorly with inhomogeneous amplitude of static (polarizing) field (B0 ) and/or
amplitude of (excitation) radiofrequency field (B1 ) fields. We propose a four
dimensional spectral-spatial fat saturation pulse that is more robust to B0/B1
inhomogeneity and also shorter than the conventional fat saturation pulse.
THEORY: The proposed pulse is tailored for local B0 inhomogeneity, which avoids
the need of a sharp transition band in the spectral domain, so it improves both
performance and pulse length. Furthermore, it can also compensate for B1
inhomogeneity. The pulse is designed sequentially by small-tip-angle
approximation design and an automatic rescaling procedure. METHODS: The proposed
method is compared to the conventional fat saturation in phantom experiments and
in vivo knee imaging at 3 T for both single-channel and parallel excitation
versions. RESULTS: Compared to the conventional method, the proposed method
produces superior fat suppression in the presence of B0 and B1 inhomogeneity and
reduces pulse length by up to half of the standard length. CONCLUSION: The
proposed four dimensional spectral-spatial fat saturation suppresses fat more
robustly with shorter pulse length than the conventional fat saturation in the
presence of B0 and B1 inhomogeneity.
PMID- 24347328
TI - Macrocyclic polyoxazoles as G-quadruplex ligands.
AB - This review deals with recent progress in the synthesis and evaluation of our
telomestatin-inspired macrocyclic polyoxazoles as G-quadruplex (G4) ligands. The
hexaoxazole derivatives (6OTDs) interact with and stabilize G4-forming
oligonucleotides, depending upon the character of the side chain functional
groups. Cationic functional groups are particularly effective due to their
secondary interaction with phosphate in the DNA backbone. On the other hand,
heptaoxazole derivatives (7OTDs) showed potent G4-binding and stabilization
activity regardless of the functional groups on the side chain. A caged G4
ligand, Y2Nv2-6OTD (7), and a fluorescent G4 ligand, L1BOD-7OTD (13), have been
synthesized.
PMID- 24347333
TI - Comparing various surgical delay methods with ischemic preconditioning in the rat
TRAM flap model.
AB - Both surgical delay and ischemic preconditioning (IP) have been shown to be
effective in improving the survival of flaps. We used a variety of flap delay
methods and IP to increase the surviving area of the transverse rectus abdominis
musculocutaneous (TRAM) flap in rats, and the results are compared in between. A
6-* 3-cm-sized TRAM flap in 40 Wistar rats was allocated into five groups. Group
1: TRAM flap was elevated from nondominant pedicle, and the flap was sutured to
the original bed. Group 2: Left superior deep epigastric vessels (SDEV) were cut;
1 week later, TRAM flap was elevated. Group 3: Only skin incision was done; 1
week later, TRAM flap was elevated. Group 4: Skin incision was done, and the left
SDEV were cut; 1 week later, TRAM flap was elevated. Group 5: TRAM flap was
elevated; IP was performed using three cycles of 10 minutes of repeated
ischemia/reperfusion (I/R) periods, and the flap was sutured to the original bed.
The surviving area of the flap was statistically significant between the control
and groups 2, 4, and 5 (p < 0.001), and groups 4 and 2 were superior to group 5.
Although preconditioning has been intensively studied for the last two decades
and partly provided its beneficial effects in I/R injury, we determined the IP
increased the surviving area of the TRAM flap but not effective as much as
surgical delay method.
PMID- 24347326
TI - Crystal structures of the fungal pathogen Aspergillus fumigatus protein
farnesyltransferase complexed with substrates and inhibitors reveal features for
antifungal drug design.
AB - Species of the fungal genus Aspergillus are significant human and agricultural
pathogens that are often refractory to existing antifungal treatments. Protein
farnesyltransferase (FTase), a critical enzyme in eukaryotes, is an attractive
potential target for antifungal drug discovery. We report high-resolution
structures of A. fumigatus FTase (AfFTase) in complex with substrates and
inhibitors. Comparison of structures with farnesyldiphosphate (FPP) bound in the
absence or presence of peptide substrate, corresponding to successive steps in
ordered substrate binding, revealed that the second substrate-binding step is
accompanied by motions of a loop in the catalytic site. Re-examination of other
FTase structures showed that this motion is conserved. The substrate- and product
binding clefts in the AfFTase active site are wider than in human FTase (hFTase).
Widening is a consequence of small shifts in the alpha-helices that comprise the
majority of the FTase structure, which in turn arise from sequence variation in
the hydrophobic core of the protein. These structural effects are key features
that distinguish fungal FTases from hFTase. Their variation results in
differences in steady-state enzyme kinetics and inhibitor interactions and
presents opportunities for developing selective anti-fungal drugs by exploiting
size differences in the active sites. We illustrate the latter by comparing the
interaction of ED5 and Tipifarnib with hFTase and AfFTase. In AfFTase, the wider
groove enables ED5 to bind in the presence of FPP, whereas in hFTase it binds
only in the absence of substrate. Tipifarnib binds similarly to both enzymes but
makes less extensive contacts in AfFTase with consequently weaker binding.
PMID- 24347334
TI - Psychological and social consequences after reconstruction of upper extremity
trauma: methods of detection and management.
AB - Upper extremity trauma and resulting disability is a stressful event and can
affect a patient's personality. Several studies have shown that this injury type
has serious psychological and/or social consequences. We systematically reviewed
the evidence on the consequences of disability after a complex trauma
(combination of soft tissue, osseous, vascular, and nerve involvement) of the
upper extremity. We tried to find out the potential crucial factors that could
determine the final hand function. In addition, we considered the challenges that
need to be addressed to eliminate the adverse or negative effects that arise from
upper limb trauma. In the literature, there is a growing interest to study
changes in patients' quality of life and return to work. Psychological morbidity
is an important part of patients' perceived general health. These issues could
play an important role in the final functional outcome of the therapy. An early
identification and treatment of trauma-related distress in patients may prevent
progression of psychological pathology and mitigate negative effects on general
health status. It may be important to evaluate the amount of psychological
distress when caring for patients with hand injuries.
PMID- 24347336
TI - Can team-based medicine prescribe trust?
PMID- 24347335
TI - Differential labour market impacts from disability onset.
AB - We estimate the causal labour market impacts of disability onset by gender, age
and education levels up to 4 years after onset using longitudinal data from the
Household Income and Labour Dynamics Australia survey and difference-in
difference propensity score matching techniques. We find lasting negative impacts
on employment, especially full-time employment, which is due more to reduced
movement into full-time employment than downshifting from full-time to part-time
work following onset. Those without post-school education qualifications are
particularly vulnerable to the impacts of onset and are more likely to be out of
work and on income support than those with qualifications up to 4 years after
onset, due in part because they have greater difficulty adjusting.
PMID- 24347337
TI - Myocarditis with hypotonic-hyporesponsive episode after multiple vaccination.
PMID- 24347338
TI - Vermiform appendix inside the sac: uncommon case of inguinal hernia.
PMID- 24347339
TI - Blue rubber bleb nevus syndrome.
PMID- 24347340
TI - Silk-molded flexible, ultrasensitive, and highly stable electronic skin for
monitoring human physiological signals.
AB - Flexible and transparent E-skin devices are achieved by combining silk-molded
micro-patterned polydimethylsiloxane (PDMS) with single-walled carbon nanotube
(SWNT) ultrathin films. The E-skin sensing device demonstrates superior
sensitivity, a very low detectable pressure limit, a fast response time, and a
high stability for the detection of superslight pressures, which may broaden
their potential use as cost-effective wearable electronics for healthcare
applications.
PMID- 24347341
TI - Structure of the female gonoduct of the viviparous teleost Poecilia reticulata
(Poeciliidae) during nongestation and gestation stages.
AB - Female teleosts do not have oviducts because Mullerian ducts do not develop.
Instead, the caudal region of the ovary, the gonoduct, connects to the exterior.
Because of the lack of oviducts in viviparous teleosts, the embryos develop in
the ovary, as an intraovarian gestation, unique in vertebrates. This is the first
study to address the histology of the gonoduct in a viviparous teleost. The
gonoduct of Poecilia reticulata was analyzed during previtellogenesis,
vitellogenesis, and gestation. The gonoduct lacks germinal cells. From deep to
superficial, the wall has simple cuboidal or columnar epithelium, loose
connective tissue, longitudinal layer of smooth muscle, and visceral peritoneum.
Cells of the immune system occur in the lumen and in the mucosa. The gonoduct was
divided in three regions: 1) cephalic, 2) middle, and 3) caudal. At the initial
part of each region, thin mucosal folds extend into the lumen. The cephalic
region forms a tubular structure with light and irregular folds. The middle
region has a wider lumen and is more irregular due to ventral invaginations and
irregular and short mucosal folds; beneath the epithelium there are melano
macrophage centers. The caudal region is delimited from the middle region by
folds; however, they are thinner than these of the other regions. Ventral
invaginations form exocrine glands, and the smooth muscle is thicker than in the
other regions. During gestation, cells of the immune system are abundant; melano
macrophage centers become larger and the glands exhibit desquamated cells. These
observations suggest roles of the gonoduct in reducing the diameter of the lumen;
receiving sperm during vitellogenesis; producing secretions, more abundant during
vitellogenesis; and in immunological activity throughout the reproductive cycle.
The ciliated epithelium and the thick muscle of the caudal region may be involved
during birth.
PMID- 24347343
TI - Taurine-induced fabrication of nano-architectured conducting polypyrrole on
biomedical titanium.
AB - In this article, taurine, one of the small biomolecules associated with bone
metabolism, is firstly utilized to induce the fabrication of nano-architectured
conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of
phosphate buffer solution (PBS). Accordingly, the possible mechanism for the
fabrication of NCPPy is proposed, which is dependent on the states of polytaurine
from the polymerization of taurine, i.e., the inability of forming polytaurine
and unordered restricted space results in taurine-incorporated and polytaurine
incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and
however, ordered restricted space constructed by polytaurine chains induces the
fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine
incorporated nanowire networks (pH 7.4).
PMID- 24347342
TI - Prohibitins role in cellular survival through Ras-Raf-MEK-ERK pathway.
AB - Prohibitins are members of a highly conserved protein family containing the
stomatin/prohibitin/flotillin/HflK/C (SPFH) domain (also known as the prohibitin
[PHB] domain) found in unicellular eukaryotes, fungi, plants, animals, and
humans. Two highly homologous members of prohibitins expressed in eukaryotes are
prohibitin (PHB; B-cell receptor associated protein-32, BAP-32) and prohibitin
2/repressor of estrogen receptor activity (PHB2, REA, BAP-37). Both PHB and
REA/PHB2 are ubiquitously expressed and are present in multiple cellular
compartments including the mitochondria, nucleus, and the plasma membrane.
Multiple functions have been attributed to the mitochondrial and nuclear PHB and
PHB2/REA including cellular differentiation, anti-proliferation, and
morphogenesis. One of the major functions of the prohibitins are in maintaining
the functional integrity of the mitochondria and protecting cells from various
stresses. In the present review, we focus on the recent research developments
indicating that PHB and PHB2/REA are involved in maintaining cellular survival
through the Ras-Raf-MEK-Erk pathway. Understanding the molecular mechanisms by
which the intracellular signaling pathways utilize prohibitins in governing
cellular survival is likely to result in development of therapeutic strategies to
overcome various human pathological disorders such as diabetes, obesity,
neurological diseases, inflammatory bowel disease, and cancer.
PMID- 24347344
TI - Short sleep duration is associated with decreased serum leptin, increased energy
intake and decreased diet quality in postmenopausal women.
AB - OBJECTIVE: Short sleep duration induces hormonal perturbations contributing to
hyperphagia, insulin resistance, and obesity. The majority of these studies are
conducted in young adults. This analysis in a large (n = 769) sample of
postmenopausal women (median age 63 years) sought to (a) confirm that sleep
duration and sleep quality are negatively correlated with circulating leptin
concentrations and (b) to examine the relationship between self-reported sleep,
dietary energy intake, and diet quality, as well as, investigate the role of
leptin in these associations. METHODS: Sleep duration/quality, insomnia, and
dietary intake were determined via self-report. Blood samples were collected
following an overnight fast to assess serum leptin concentration. All analyses
were adjusted for total body fat mass. RESULTS: Women reporting <=6 hr
sleep/night had lower serum leptin concentrations than those reporting >=8 hr
sleep (P = 0.04). Furthermore, those with <=6 hr sleep/night reported higher
dietary energy intake (P = 0.01) and lower diet quality (P = 0.04) than the
reference group (7 hr sleep/night). Women sleeping >=8 hr also reported lower
diet quality than the reference group (P = 0.02). Importantly, serum leptin did
not confound these associations. CONCLUSIONS: These results provide evidence that
sleep duration is inversely associated with serum leptin and dietary energy
intake in postmenopausal women.
PMID- 24347345
TI - Hydroxytyrosol attenuates tunicamycin-induced endoplasmic reticulum stress in
human hepatocarcinoma cells.
AB - SCOPE: Hydroxytyrosol (HT) is a phenolic compound peculiarly abundant in olives
and it is being recognized as a protector of LDL from oxidation. In addition to
lipid oxidation, one emerging risk factor for cardiovascular disease is ER
stress. We tested the effect of HT on the modulation of ER stress in HepG2 cells.
METHODS AND RESULTS: HepG2 cells were treated with 1 MUM and 5 MUM of HT and 100
MUM lipoic acid (LA) and glutathione-ethyl ester (GSH), for 24 h. Induction of
the unfolded protein response (UPR) was initiated by treatment with 2 MUg/mL
tunicamycin for 4 h. Real time RT-PCR analyses followed by Western blot and ELISA
of different ER stress markers revealed that the protective activities of HT were
superior to those of two known thiolic antioxidants, i.e., LA and GSH.
CONCLUSION: Mounting evidence indicates the ER as an important target of dietary
or pharmacological intervention. In this paper, we report the modulatory
activities of physiological concentrations of HT toward ER stress and we shed
some light on pathways alternative to the well-known antioxidant mechanisms,
through which olive oil phenolics modulate cell signaling and could impact
cardiovascular health and degenerative diseases.
PMID- 24347346
TI - iHEA student competition 'Young Researchers in Health Economics'.
PMID- 24347347
TI - Automatic cardiac LV segmentation in MRI using modified graph cuts with
smoothness and interslice constraints.
AB - PURPOSE: Magnetic resonance imaging (MRI), specifically late-enhanced MRI, is the
standard clinical imaging protocol to assess cardiac viability. Segmentation of
myocardial walls is a prerequisite for this assessment. Automatic and robust
multisequence segmentation is required to support processing massive quantities
of data. METHODS: A generic rule-based framework to automatically segment the
left ventricle myocardium is presented here. We use intensity information, and
include shape and interslice smoothness constraints, providing robustness to
subject- and study-specific changes. Our automatic initialization considers the
geometrical and appearance properties of the left ventricle, as well as
interslice information. The segmentation algorithm uses a decoupled, modified
graph cut approach with control points, providing a good balance between
flexibility and robustness. RESULTS: The method was evaluated on late-enhanced
MRI images from a 20-patient in-house database, and on cine-MRI images from a 15
patient open access database, both using as reference manually delineated
contours. Segmentation agreement, measured using the Dice coefficient, was 0.81+/
0.05 and 0.92+/-0.04 for late-enhanced MRI and cine-MRI, respectively. The method
was also compared favorably to a three-dimensional Active Shape Model approach.
CONCLUSION: The experimental validation with two magnetic resonance sequences
demonstrates increased accuracy and versatility.
PMID- 24347348
TI - Reply to the article Espinos JC, Turro R, Mata A, Cruz M, da Costa M, Villa V,
Buchwald JN, Turro J. Early experience with the Incision less Operating
PlatformTM (IOP) for the treatment of obesity: the Primary Obesity Surgery
Endolumenal (POSE) procedure. Obes Surg. 2013;23:1375-83.
PMID- 24347349
TI - Evolution of subclinical hypothyroidism and its relation with glucose and
triglycerides levels in morbidly obese patients after undergoing sleeve
gastrectomy as bariatric procedure.
AB - BACKGROUND: There is an increased prevalence of subclinical hypothyroidism (SCH)
in patients with obesity. It is unclear if this biochemical abnormality may be a
secondary phenomenon of obesity or a real hypothyroid state. METHODS: A
retrospective study of all the morbidly obese patients undergoing laparoscopic
sleeve gastrectomy as bariatric procedure between October 2007 and November 2012
was performed. Weight loss, body mass index (BMI) and excess weight loss,
baseline glucose, lipid profiles, and TSH levels were obtained before operation
and postoperative determinations at 3, 6, and 12 months after surgery. RESULTS:
Sixty patients were included. Prevalence of subclinical hypothyroidism was 16.7%
preoperatively, 10% at 3 months, 3.3% at 6 months, and 1.7% at 12 months. A
significant correlation could be established between TSH decrease and weight loss
at 12 months (Pearson 0.603; p = 0.007). TSH decrease showed a significant
correlation with glucose and glycated hemoglobin decrease from 6th month onwards.
Referring to lipid profile, an association of TSH decrease with total
cholesterol, LDL cholesterol, or HDL cholesterol could not be determined. A
significant association between TSH decrease and triglycerides and cardiovascular
risk index triglycerides/HDL cholesterol reductions could also be established 12
months after surgery. CONCLUSIONS: SCH is usually corrected after bariatric
surgery, while there are no significant changes in total or LDL cholesterol. This
suggests that, in morbidly obese subjects, SCH is, in most patients, just a
consequence of the abnormal fat accumulation and not a real hypothyroid state.
PMID- 24347350
TI - Management of anastomotic ulcers after Roux-en-Y gastric bypass: results of an
international survey.
AB - BACKGROUND: Anastomotic ulcers (AUs) after Roux-en-Y gastric bypass (RYGB) occur
in up to 16% of patients. In an international survey among members of the
International Federation for the Surgery of Obesity and Metabolic Disorders
(IFSO), current preventative and therapeutic strategies in AU were analyzed.
METHODS: An Internet-based survey was performed. RESULTS: One hundred eighty-nine
surgeons completed the survey. Preoperative screening for Helicobacter pylori is
performed by 65%. Eighty-eight percent of them prophylactically prescribe
antacids for 3 months after surgery (interquartile range (IQR) 1-6). In case of
AU, 99% of participants opt for proton pump inhibitors (PPIs) either alone (60%)
or in combination with sucralfate (39%). After ulcer resolution, 52% continue PPI
for 6 (3-6) months. In case of AU recurrence, 56% continue with conservative
treatment. In contrast, 41% of them favor a renewal of the gastrojejunal
anastomosis either combined with truncal vagotomy (18%) or with gastric remnant
resection (13%), and only 2% choose to resect both gastric pouch and gastric
remnant with subsequent reconstruction by esophagojejunostomy. In case of
recurrence after surgical revision, 46% of participants opt again for a
conservative approach, while 36% chose to redo the gastrojejunostomy once again.
CONCLUSIONS: The majority of bariatric surgeons recommend preoperative screening
and eradication of H. pylori as well as prophylactic use of PPI. If an AU is
diagnosed, the role of PPI as a first-line treatment seems to be undisputed.
However, dosage and duration of therapy remain unclear. In refractory AU, there
is no consensus among bariatric surgeons whether conservative treatment or
surgical revision should be performed.
PMID- 24347351
TI - Prophylactic glycopyrrolate reduces hypotensive responses in elderly patients
during spinal anesthesia: a randomized controlled trial.
AB - BACKGROUND: Hypotension during spinal anesthesia is a serious complication in
elderly patients. We evaluated the effect of glycopyrrolate on hypotensive
responses in elderly patients undergoing spinal anesthesia. METHODS: Sixty-six
patients older than 60 yr of age scheduled for elective surgery with spinal
anesthesia were included in the study. They received either glycopyrrolate 0.2 mg
(group G) or normal saline (group C) intramuscularly 15 min before spinal
anesthesia. The following outcomes were evaluated after the induction of spinal
anesthesia: the incidence of hypotension and bradycardia, the ephedrine
requirement, mean arterial pressure, heart rate, and the incidence of nausea and
vomiting. RESULTS: Twenty-three of 33 (70.0%) patients in group C experienced
hypotension compared with nine of 33 (27.3%) patients in group G (difference =
42.7%; 95% confidence interval [CI]: 18.4 to 60.2; P = 0.001). The median
[interquartile range] amount of ephedrine required was 5 [0-15] mg in group C
compared with 0 [0-5] mg in group G (difference = 5.0 mg; 95% CI: 2.7 to 7.3; P =
0.001). Nine (27.3%) patients in group C experienced nausea and vomiting compared
with 2 (6.1%) in group G (difference = 21.2%; 95% CI: 3.0 to 38.7; P = 0.044).
Three (9.1%) patients in group C experienced bradycardia compared with 1 (3.0%)
patient in group G (difference = 6.1%; 95% CI: -7.6 to 20.8; P = 0.613).
CONCLUSION: Prophylactic intramuscular glycopyrrolate reduced the occurrence and
severity of hypotensive responses, the requirement for ephedrine, and the
incidence of nausea and vomiting in elderly patients undergoing spinal
anesthesia. The trial was registered at the Clinical Research Information
Service, Republic of Korea (KCT0000556).
PMID- 24347352
TI - Delayed recovery post anesthesia: an atypical presentation of familial hemiplegic
migraine.
PMID- 24347354
TI - Review of a high-risk obstetric anesthesia antepartum consult clinic.
PMID- 24347355
TI - Estimation of equivalent threshold currents using different pulse widths for the
epidural stimulation test in a porcine model.
AB - BACKGROUND: The epidural stimulation test can help detect if a catheter is
correctly positioned in the epidural space. Previous studies showed that a
current of up to 16 mA was required to elicit a motor response, but few
peripheral nerve stimulators can produce a current this high. Manipulating pulse
width can produce a positive response at a lower current. To clarify the effects
of pulse width on the epidural stimulation test, we performed a single-blinded
study in a porcine model to estimate the equivalent current needed at varying
pulse widths. METHODS: After obtaining local ethics approval, an 18G insulated
Tuohy needle was advanced into the epidural space at the lower lumbar spinal
level, and a 20G stimulating epidural catheter was advanced 30 cm cephalad. A
gradually increasing electrical current was applied, and a motor response was
elicited at pulse widths of 0.1, 0.2, 0.3, 0.5, and 1 msec. This was followed by
a 1-2 cm catheter withdrawal, and the process was repeated for a total of 15
locations per pig. RESULTS: Recorded threshold currents ranged from 0.36-9.5 mA
at a pulse width of 0.2 msec. Our results show a linear relationship between
threshold current and pulse width. CONCLUSIONS: In situations where different
pulse widths are needed, the nomograms presented here may be useful to estimate
the equivalent threshold current which is required to elicit a motor response
according to previously published criteria for epidural stimulation tests.
PMID- 24347356
TI - Liver remnant regeneration in donors after living donor liver transplantation:
long-term follow-up using CT and MR imaging.
AB - PURPOSE: To assess liver remnant volume regeneration and maintenance, and
complications in the long-time follow-up of donors after living donor liver
transplantation using CT and MRI. MATERIALS AND METHODS: 47 donors with a mean
age of 33.5 years who donated liver tissue for transplantation and who were
available for follow-up imaging were included in this retrospective study.
Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two
observers evaluated pre- and postoperative images regarding anatomy and
pathological findings. Volumes were manually measured on contrast-enhanced images
in the portal venous phase, and potential postoperative complications were
documented. Pre- and postoperative liver volumes were compared for evaluating
liver remnant regeneration. RESULTS: 47 preoperative and 89 follow-up studies
covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL)
donation, the mean liver remnant volume was 522.0 ml (+/- 144.0; 36.1 %; n = 18),
after left lateral section (LLS) donation 1,121.7 ml (+/- 212.8; 79.9 %; n = 24),
and after left liver lobe (LLL) donation 1,181.5 ml (+/- 279.5; 72.0 %; n = 5).
Twelve months after donation, the liver remnant volume were 87.3 % (RLL; +/-
11.8; n = 11), 95.0 % (LS; +/- 11.6; n = 18), and 80.1 % (LLL; +/- 2.0; n = 2
LLL) of the preoperative total liver volume. Rapid initial regeneration and
maintenance at 80 % of the preoperative liver volume were observed over the total
follow-up period. Minor postoperative complications were found early in 4
patients. No severe or late complications or mortality occurred. CONCLUSION:
Rapid regeneration of liver remnant volumes in all donors and volume maintenance
over the long-term follow-up period of up to 84 months without severe or late
complications are important observations for assessing the safety of LDLT donors.
KEY POINTS: Liver remnant volumes of LDLT donors rapidly regenerated after
donation and volumes were maintained over the long-term follow-up period of up to
84 months without severe or late complications.
PMID- 24347357
TI - [Increased dyspnea after airbag rupture].
PMID- 24347358
TI - [Pulmonary differentiation -/ATRA syndrome within the scope of therapy of acute
promyelocytic leukemia (APL)].
PMID- 24347359
TI - MRI-guided and CT-guided cervical nerve root infiltration therapy: a cost
comparison.
AB - PURPOSE: To evaluate and compare the costs of MRI-guided and CT-guided cervical
nerve root infiltration for the minimally invasive treatment of radicular neck
pain. MATERIALS AND METHODS: Between September 2009 and April 2012, 22 patients
(9 men, 13 women; mean age: 48.2 years) underwent MRI-guided (1.0 Tesla, Panorama
HFO, Philips) single-site periradicular cervical nerve root infiltration with 40
mg triamcinolone acetonide. A further 64 patients (34 men, 30 women; mean age:
50.3 years) were treated under CT fluoroscopic guidance (Somatom Definition 64,
Siemens). The mean overall costs were calculated as the sum of the prorated costs
of equipment use (purchase, depreciation, maintenance, and energy costs),
personnel costs and expenditure for disposables that were identified for MRI- and
CT-guided procedures. Additionally, the cost of ultrasound guidance was
calculated. RESULTS: The mean intervention time was 24.9 min. (range: 12 - 36
min.) for MRI-guided infiltration and 19.7 min. (range: 5 - 54 min.) for CT
guided infiltration. The average total costs per patient were EUR 240 for MRI
guided interventions and EUR 124 for CT-guided interventions. These were (MRI/CT
guidance) EUR 150/60 for equipment use, EUR 46/40 for personnel, and EUR 44/25
for disposables. The mean overall cost of ultrasound guidance was EUR 76.
CONCLUSION: Cervical nerve root infiltration using MRI guidance is still about
twice as expensive as infiltration using CT guidance. However, since it does not
involve radiation exposure for patients and personnel, MRI-guided nerve root
infiltration may become a promising alternative to the CT-guided procedure,
especially since a further price decrease is expected for MRI devices and MR
compatible disposables. In contrast, ultrasound remains the less expensive method
for nerve root infiltration guidance.
PMID- 24347360
TI - Comparison of 3D cube FLAIR with 2D FLAIR for multiple sclerosis imaging at 3
Tesla.
AB - PURPOSE: Three-dimensional (3 D) MRI sequences allow improved spatial resolution
with good signal and contrast properties as well as multiplanar reconstruction.
We sought to compare Cube, a 3 D FLAIR sequence, to a standard 2 D FLAIR sequence
in multiple sclerosis (MS) imaging. MATERIALS AND METHODS: Examinations were
performed in the clinical routine on a 3.0 Tesla scanner. 12 patients with
definite MS were included. Lesions with MS-typical properties on the images of
Cube FLAIR and 2 D FLAIR sequences were counted and allocated to different brain
regions. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were
calculated. RESULTS: With 384 the overall number of lesions found with Cube FLAIR
was significantly higher than with 2 D FLAIR (N = 221). The difference was mostly
accounted for by supratentorial lesions (N = 372 vs. N = 216) while the
infratentorial lesion counts were low in both sequences. SNRs and CNRs were
significantly higher in CUBE FLAIR with the exception of the CNR of lesion to
gray matter, which was not significantly different. CONCLUSION: Cube FLAIR showed
a higher sensitivity for MS lesions compared to a 2 D FLAIR sequence. 3 D FLAIR
might replace 2 D FLAIR sequences in MS imaging in the future.
PMID- 24347361
TI - Facile synthesis of anatase TiO(2) quantum-dot/graphene-nanosheet composites with
enhanced electrochemical performance for lithium-ion batteries.
AB - A facile method to synthesize well-dispersed TiO2 quantum dots on graphene
nanosheets (TiO2 -QDs/GNs) in a water-in-oil (W/O) emulsion system is reported.
The TiO2 /graphene composites display high performance as an anode material for
lithium-ion batteries (LIBs), such as having high reversible lithium storage
capacity, high Coulombic efficiency, excellent cycling stability, and high rate
capability. The excellent electrochemical performance and special structure of
the composites thus offer a way to prepare novel graphene-based electrode
materials for high-energy-density and high-power LIBs.
PMID- 24347362
TI - Comprehensive integrated care for patients with sickle cell disease in a remote
aboriginal tribal population in southern India.
AB - BACKGROUND: Healthcare delivery for sickle cell disease (SCD) can be challenging,
in low resource settings. We studied the feasibility of delivering comprehensive
SCD care in a community-based network for remote, economically, and socially
disadvantaged tribes in Gudalur, India. PROCEDURE: We reviewed medical records
for all patients followed at the Gudalur Adivasi Hospital. We used published
quality of care indicators to benchmark screening and routine healthcare
maintenance. RESULTS: We screened 9,646 individuals (60.4%) under the age of 30
of a population of 25,000 individuals. Of 111 active patients with SCD, 71% have
had at least one annual comprehensive clinic visit at a median visit interval of
57 days. We provided pneumococcal immunization and penicillin prophylaxis to 56
(50%) patients and HU to 68 (61%). Median spleen size was 1 cm (range 1-6 cm),
mean was Hb 9.3 g/dl and we reported a mean of 0.7 painful episodes/year.
Premature deaths occurred in 19 patients at a median age of 23 years due to acute
chest syndrome, sepsis, severe anemia, stroke, mesenteric infarction, puerperal
sepsis, or sudden unexplained death. Healthcare maintenance met 11 of 17
published SCD quality of care indicators. Average cost was 1,343 Indian Rupees
(INR) (approximately US$ 25) per hospitalization and 173 INR (approximately US$
4) per clinic visit. CONCLUSION: High quality comprehensive care for SCD can be
delivered for a low income, aboriginal population in India through a community
driven network of care. This model can serve as a template for healthcare
delivery for SCD in low-income communities.
PMID- 24347363
TI - Detection of colorectal cancer and adenomas by FDG-PET cancer screening program:
results based on a nationwide Japanese survey.
AB - PURPOSE: The aim of this study was to analyze the detection rate for CRC and
adenomas for asymptomatic subjects in Japan by FDG-PET cancer screening program
carried out between 2006 and 2009. METHODS: The "FDG-PET cancer screening
program" included both PET and positron emission tomography with computed
tomography (PET/CT) with or without other screening tests. A total of 154,783
asymptomatic subjects underwent FDG-PET cancer screening program; we analyzed the
1,808 cases with findings from any detection method that indicated suspected CRC.
RESULTS: Among the 1,808 cases, the number of cases verified as CRC and adenoma
was 394 and 679, respectively. The sensitivity and positive predictive value
(PPV) of FDG-PET were 86.0 and 31.7% for CRC, and 63.6 and 63.8% for CRC and
adenoma. The sensitivity and PPV of fecal occult blood test (FOBT) for CRC were
lower than those of FDG-PET, but higher for adenoma. Therefore, FDG-PET and FOBT
were complementary for screening for CRC, and CRC and adenoma. The majority of
CRC detected by the FDG-PET imaging was UICC stage 0 or I, however, detection of
smaller or less invasive cancer was limited. CONCLUSION: The FDG-PET screening
program in Japan has detected CRC at an early stage and adenomas as premalignant
lesions. A combination of FDG-PET and FOBT yields the best results if the intent
is to detect either CRC or adenoma. However, it is absolutely clear that an FDG
PET cancer screening program cannot detect all colon lesions.
PMID- 24347364
TI - Sleep surgery and medical malpractice.
AB - OBJECTIVES/HYPOTHESIS: To describe and analyze the causes and outcomes of
lawsuits pertaining to sleep surgery to mitigate future litigation and improve
physician education. STUDY DESIGN: A retrospective review of a publicly available
database containing jury verdicts and settlements. METHODS: The LexisNexis MEGA
Jury Verdicts and Settlements database was reviewed for all lawsuits including
settlements and trial verdicts related to sleep surgery. Data including type of
surgery performed, plaintiff allegation, nature of injury, outcomes, and
indemnities were collected and analyzed. RESULTS: Fifty-one cases met the
inclusion criteria. Of these, 30 were decided by a jury, nine were settled out of
court, and 10 were resolved by other means. Overall, 57% of known outcomes
favored the defendant. The most common surgery performed was tonsillectomy (57%),
followed by uvulopalatopharyngoplasty (45%), adenoidectomy (31%), and septoplasty
(31%). No difference was found between outcomes when comparing the most common
injuries cited, including wrongful death (P = .572), airway compromise (P =
.376), and drug reaction (P = .443). If failure to recognize a complication (P =
.034) or delay in diagnosis (P = .026) was a component of the legal allegations,
the outcome significantly favored the plaintiff. The median settlement ($545,000)
and plaintiff award ($1.45 million) were not significantly different (P = .13).
CONCLUSIONS: The majority of outcomes favored the defendant. Type of injury did
not predict outcome. Failure to recognize complications and delay in diagnosis
strongly predicted a verdict in favor of the plaintiff. LEVEL OF EVIDENCE: 2c.
PMID- 24347365
TI - Role of the extracellular matrix in whole organ engineering.
AB - End-stage organ failure is a devastating problem with limited therapeutic
options. The definitive treatment is orthotropic transplantation, however, there
exists a severe shortage of viable donor organs, and this shortage is worsening
with an aging demographic and as the number of new cases of organ failure
increases. Patients fortunate enough to receive a transplant are required to
receive immunosuppressive therapies and can face transplant rejection. The
emerging concept of organ engineering may offer a new hope for these patients.
Researchers in the field of regenerative medicine and tissue engineering are
using three-dimensional whole organ scaffolds composed of allogeneic or
xenogeneic extracellular matrix (ECM) for engineering functional tissue suitable
for transplantation. Perfusion decellularization is an approach that generates
native ECM scaffolds with intact 3D anatomical architecture and vasculature.
Decellularized organs provide the ideal transplantable scaffold with all the
necessary microstructure and extracellular cues for cell attachment,
differentiation, vascularization, and function. The present manuscript will
review the role of the ECM in normal development, the concept of ECM tissue
specificity, and the effect of processing methods on eventual clinical outcomes.
An overview of existing challenges and future directions will also be discussed.
PMID- 24347366
TI - Dental patterning in the earliest sharks: Implications for tooth evolution.
AB - Doliodus problematicus is the oldest known fossil shark-like fish with an almost
intact dentition (Emsian, Lower Devonian, c. 397Ma). We provide a detailed
description of the teeth and dentition in D. problematicus, based on tomographic
analysis of NBMG 10127 (New Brunswick Museum, Canada). Comparisons with modern
shark dentitions suggest that Doliodus was a ram-feeding predator with a
dentition adapted to seizing and disabling prey. Doliodus provides several clues
about the early evolution of the "shark-like" dentition in chondrichthyans and
also raises new questions about the evolution of oral teeth in jawed vertebrates.
As in modern sharks, teeth in Doliodus were replaced in a linguo-labial sequence
within tooth families at fixed positions along the jaws (12-14 tooth families per
jaw quadrant in NBMG 10127). Doliodus teeth were replaced much more slowly than
in modern sharks. Nevertheless, its tooth formation was apparently as highly
organized as in modern elasmobranchs, in which future tooth positions are
indicated by synchronized expression of shh at fixed loci within the dental
epithelium. Comparable dental arrays are absent in osteichthyans, placoderms, and
many "acanthodians"; a "shark-like" dentition, therefore, may be a synapomorphy
of chondrichthyans and gnathostomes such as Ptomacanthus. The upper anterior
teeth in Doliodus were not attached to the palatoquadrates, but were instead
supported by the ethmoid region of the prechordal basicranium, as in some other
Paleozoic taxa (e.g., Triodus, Ptomacanthus). This suggests that the
chondrichthyan dental lamina was originally associated with prechordal
basicranial cartilage as well as jaw cartilage, and that the modern elasmobranch
condition (in which the oral dentition is confined to the jaws) is
phylogenetically advanced. Thus, oral tooth development in modern elasmobranchs
does not provide a complete developmental model for chondrichthyans or
gnathostomes.
PMID- 24347367
TI - The linea aspera: a virtual case study testing emergence of form and function.
AB - The linea aspera (LA) forms a characteristic ridge along the posterior aspect of
the human femur. Absent in youth, the LA emerges during early puberty and becomes
more prominent with advancing age. Pauwels, a pioneer of mechanobiology,
hypothesized that the LA forms in the precise location where axial intracortical
stresses are greatest, effectively "stiffening" the femur in bending. This study
reassesses the mechanical role of the LA in virtual models of human femora,
accounting for increasing prominence of the LA at juvenile, young adult and aged
stages. Using finite element analysis, peak stresses and the relationship between
the LA, neutral axis and centroidal axes (CAs) are evaluated for cross-sections
along the mid-diaphysis of the virtual femora. Additionally, the relationship
between LA and CAs is studied in anatomical cross-sections from Pauwels'
manuscript as well as aged cadaveric donors, indicating that his conclusion may
have been stymied by lack of modern computational methods. The results of the
current study do not support a mechanical role of the LA as its emergence results
in less than a 3% decrease in peak stress, while increasing prominence of the LA
also serves to rotate CAs away from calculated stress field, implicating a less
"bone centric" view of form and function.
PMID- 24347368
TI - Directing self-assembly of nanoscopic cylindrical diblock brush terpolymers into
films with desired spatial orientations: expansion of chemical composition scope.
AB - Diblock brush terpolymers (DBTs) with different fluorinated methacrylate-based
block segments are synthesized through sequential ring-opening metathesis
polymerizations and are used to prepare polymer thin films with predictable film
thicknesses. These DBTs exhibit preferable substrate vertical alignments within
the films, induced by the relatively lower surface energy of the fluorinated
structural components, together with the overall cylindrical morphology of the
brush architecture.
PMID- 24347369
TI - Modeling intention to participate in face-to-face and online lung cancer support
groups.
AB - BACKGROUND: Lung cancer patients and survivors are significantly less likely to
use support groups than those with other cancers. In this study, we evaluated the
utility and specificity of the Behavioral Model for Vulnerable Populations for
modeling intention to participate in face-to-face (F2F) and online lung cancer
support groups. METHODS: Adults diagnosed with lung cancer (n = 230) completed
measures assessing predisposing, enabling, and need factors associated with
intention to use support services. RESULTS: Intention to join a F2F support group
(found among 36.4% of survivors) was associated with positive attitude about F2F
support groups, fewer perceived time constraints, less travel time from the
clinic, and not having enough social support. Intention to join an online support
group (34% of survivors) was associated with having more positive attitudes about
online support, greater use of avoidance coping strategies, more comfort using
computers, and fewer perceived time constraints. Demographics, medical history,
health status, and psychological status were not associated with intention to
join either type of group. CONCLUSIONS: Reducing barriers to participation and
addressing attitudes about support services may be the most effective ways to
increase utilization of lung cancer support services.
PMID- 24347370
TI - A ranking of diffusion MRI compartment models with in vivo human brain data.
AB - PURPOSE: Diffusion magnetic resonance imaging (MRI) microstructure imaging
provides a unique noninvasive probe into tissue microstructure. The technique
relies on biophysically motivated mathematical models, relating microscopic
tissue features to the magnetic resonance (MR) signal. This work aims to
determine which compartment models of diffusion MRI are best at describing
measurements from in vivo human brain white matter. METHODS: Recent work shows
that three compartment models, designed to capture intra-axonal, extracellular,
and isotropically restricted diffusion, best explain multi-b-value data sets from
fixed rat corpus callosum. We extend this investigation to in vivo by using a
live human subject on a clinical scanner. The analysis compares models of one,
two, and three compartments and ranks their ability to explain the measured data.
We enhance the original methodology to further evaluate the stability of the
ranking. RESULTS: As with fixed tissue, three compartment models explain the data
best. However, a clearer hierarchical structure and simpler models emerge. We
also find that splitting the scanning into shorter sessions has little effect on
the ranking of models, and that the results are broadly reproducible across
sessions. CONCLUSION: Three compartments are required to explain diffusion MR
measurements from in vivo corpus callosum, which informs the choice of model for
microstructure imaging applications in the brain.
PMID- 24347371
TI - Altered human gut dendritic cell properties in ulcerative colitis are reversed by
Lactobacillus plantarum extracellular encrypted peptide STp.
AB - SCOPE: The human/microbiota cross-talk is partially mediated by bacteria-derived
peptides like Serine-Threonine peptide (STp), which is resistant to gut
proteolysis, is found in the human healthy colon and induces regulatory
properties on gut dendritic cells (DCs); here we characterized human gut DC in
ulcerative colitis (UC) patients and studied the effect of STp on their
properties. METHODS AND RESULTS: Human colonic DC from healthy controls and UC
patients were isolated, conditioned for 24 h +/- STp and characterized by flow
cytometry, immunohistochemistry, and electron microscopy. Expression of immature
DC markers DC-SIGN and ILT3, and Toll-like receptors were increased on gut UC-DC.
Langerin (involved in phagocytosis), lymph node homing marker CCR7, and
activation markers CD40/CD80/CD86 were decreased in UC. Gut DC had restricted
stimulatory capacity for T-cells in UC. Conditioning of DC with STp in vitro
reduced Toll-like receptor expression, increased CD40 and CD80 expression, and
restored their stimulatory capacity. CONCLUSION: Colonic DCs display an abnormal
immature phenotype in UC, which was partially restored following STp treatment.
Bacteria-derived metabolites, like STp, seem to have a role in gut homeostasis
that is missing in UC so they might lead a new era of probiotic products setting
the basis for nondrug dietary therapy in inflammatory bowel disease.
PMID- 24347372
TI - Autophagy during early stages contributes to bovine viral diarrhea virus
replication in MDBK cells.
AB - Autophagy (or autophagocytosis) is an essential and precise control process by
which cells degrade unnecessary or dysfunctional cellular components or
organelles in the cytoplasm in response to nutrient depletion, exogenous
pathogens, or other stimuli. This process results in the removal of damaged or
surplus organelles and macromolecular complexes via a lysosome-dependent
mechanism. Bovine viral diarrhea virus (BVDV) is a ssRNA virus of the
Flaviviridae family (genus Pestivirus). BVDV infection results in major economic
losses due to poor reproductive performance and poor calf performance in cattle
herds. In our previous studies, we have shown that BVDV NADL infection
significantly increases autophagy in MDBK cells. To further define the
interactions between autophagy and BVDV infection, we investigated the effects of
autophagy on the replication of BVDV NADL. The findings showed that autophagy was
inhibited by treatment with 3-methyladenine (3-MA) or wortmannin and that the
knockdown of LC3 and Beclin1 using lentivirus-mediated RNA interference (RNAi)
suppressed BVDV NADL replication. In contrast, the findings showed the
replication of BVDV NADL was significantly increased by treatment with the
autophagy inducer rapamycin within 18 h post-infection (pi). However, the mRNA
levels of BVDV NADL 5'UTRs showed a downward trend after 18 h pi, and this effect
was reversed by chloroquine treatment. Therefore, we inferred that infection with
BVDV NADL increases autophagy, which in turn favors BVDV NADL replication at
early stages.
PMID- 24347373
TI - MALDI mass spectrometry imaging of 1-methyl-4-phenylpyridinium (MPP+) in mouse
brain.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder
affecting ~1% of the population older than 60 years. The administration of the
proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is one
of the most widely used approach to elucidate the mechanisms of cell death
involved in PD. Its toxicity is attributed to its active metabolite 1-methyl-4
phenylpyridinium (MPP(+)). However, the magnitude of the PD-like
neurodegeneration induced by MPTP depends on many variables, including the route
of administration. Different groups, including us, demonstrated that intranasal
(i.n.) administration of MPTP constitutes a new route of toxin delivery to the
brain that mimics environmental exposure to neurotoxins. In particular, our
previous data showed that mice submitted to acute i.n. MPTP administration
displayed a significant decrease of striatal dopamine (DA) and a loss of
dopaminergic (DA) neurons in the substantia nigra pars compacta. However, little
is known about the timing and the anatomical distribution of MPP(+) after i.n.
MPTP administration in mice. In the present study, C57BL/6J mice received one
dose of i.n. MPTP (1 mg/nostril) and were sacrificed at two different times after
the administration. Using matrix-assisted laser desorption-ionization mass
spectrometry imaging, a new technique for the detection of endogenous unlabeled
molecules in tissue sections, we showed for the first time the MPP(+) anatomical
distribution in different brain regions. We demonstrated that the toxin first
reached almost all the brain areas; however, in a second time MPP(+) remained
highly concentrated in the olfactory bulb, the basal ganglia, the ventral
mesencephalon, and the locus coeruleus, regions differently affected in PD.
PMID- 24347375
TI - DNA-mediated construction of hollow upconversion nanoparticles for protein
harvesting and near-infrared light triggered release.
AB - A simple DNA-mediated solvothermal method has been developed for the construction
of well-defined hollow UNPs that can be used for a new paradigm to realize NIR
light-controlled non-invasive protein release. In vitro studies show that the
UNPs are capable of the transportation of enzyme into living cells. Intracellular
NIR triggers the release of enzymes with high spatial and temporal precision and
the released enzyme also retains its biological activity.
PMID- 24347374
TI - Enhanced mossy fiber sprouting and synapse formation in organotypic hippocampal
cultures following transient domoic acid excitotoxicity.
AB - We have previously reported evidence of BDNF upregulation and increased
neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after a
transient excitotoxic injury to the hippocampal CA1 area induced by low
concentrations of the AMPA/kainate receptor agonist domoic acid (DOM). The
changes observed in OHSC were consistent with observations in vivo, where low
concentrations of DOM administered to rats during perinatal development caused
increased BDNF and TrkB expression in the resulting adult animals. The in vivo
low dose-DOM treatment also results in permanent alterations in hippocampal
structure and function, including abnormal formation of dentate granule cell
axons projecting to area CA3 (mossy fiber sprouting). Our objective in the
current study is to determine if low concentrations of DOM induce mossy fiber
sprouting and/or synaptogenesis in OHSC in order to facilitate future studies on
the mechanisms of structural hippocampal plasticity induced by DOM. We report
herein that application of a low concentration of DOM (2 MUM) for 24 h followed
by recovery induced a significant increase in the expression of the mossy fiber
marker ZnT3 that progressed over time in culture. The DOM insult (2 MUM, 24 h)
also resulted in a significant upregulation of both the presynaptic marker
synaptophysin and the postsynaptic marker PSD-95. All of the observed effects
were fully antagonized by co-administration of the AMPA/kainate antagonists CNQX
or NBQX but only partly by the NMDA antagonist CPP and not by the calcium channel
blocker nifedipine. We conclude that exposure of OHSC to concentrations of DOM
below those required to induce permanent neurotoxicity can induce a progressive
change in hippocampal structure that can effectively model DOM effects in vivo.
PMID- 24347376
TI - Health-related quality of life in children and young adults with post-thrombotic
syndrome: results from a cross-sectional study.
AB - OBJECTIVE: While post-thrombotic syndrome (PTS) is increasingly recognized in
children with a history of deep vein thrombosis (DVT), its impact on the health
related quality of life (HRQoL) is unknown. Our objective was to evaluate the
association between the PTS and HRQoL by surveying a cohort of patients treated
at our institution for DVT. MATERIALS/METHODS: All unique pediatric patients (0
18 years) treated for a DVT at the Mayo Clinic during the 15-year period, 1995
2009 were identified. A previously validated PTS survey instrument and age
appropriate Pediatric Quality of Life inventory, version 4 (PedsQL 4.0) were
mailed to eligible patients. Linear regression models were fit to compare the
HRQoL scores between PTS groups (none, mild, moderate/severe), after adjusting
for the presence of potential covariates. RESULTS: Of the 90 respondents, 65
(72%) reported signs and/or symptoms of PTS. Mean age (+/- SD) at DVT diagnosis
and survey completion were 12.8 (+/- 6.1) and 19.3 (+/- 7.7) years, respectively.
Self-report PedsQL 4.0 module was completed by 79 patients, and 34 guardians
completed the parent-proxy module. Patients with moderate to severe PTS reported
significantly worse total HRQoL score (mean +/- SD, 71.3 +/- 13.4) as compared to
patients with mild PTS (84.8 +/- 14.2) and no PTS (83.4 +/- 14) (P = 0.001).
CONCLUSION: Moderate to severe PTS has a significant impact on self-reported
HRQoL as measured using the generic PedsQL 4.0. Further research is warranted to
develop a venous disease-specific quality of life measure for children with a
history of DVT.
PMID- 24347377
TI - Venous thrombosis in rare or unusual sites: a diagnostic challenge.
AB - Venous thrombosis usually involves the veins of the limbs, most frequently the
leg veins. All other venous districts may sometimes be affected by the thrombotic
process. Sometimes, the thrombotic occlusion of the veins of a given region show
typical signs and symptoms. In other cases, the picture may not be clear and a
high degree of clinical suspicion is needed for a correct approach to patient
diagnosis and management. Thrombosis of retinal and jugular veins, right heart
thrombosis including thrombosis of coronary sinus and thrombosis of the azygos
system may be included in this group. In addition, thromboses of umbilical,
renal, ovarian, spermatic, and iliac veins also require attention. Finally, the
dorsal veins of the penis may also be affected by thrombotic events. The main
clinical features of these thromboses are reviewed herein with suggestions for a
correct diagnostic approach. The importance of sonography and of other imaging
techniques is emphasized. A prompt diagnosis is of paramount importance as most
of these thromboses in rare or unusual sites may still cause severe systemic
complications (pulmonary embolism, sepsis, and heart failure).
PMID- 24347378
TI - 2-Bromo-6-[(18) F]fluoropyridine: two-step fluorine-18 radiolabelling via
transition metal-mediated chemistry.
AB - Novel radiolabelling methods are important for the development of new tracers for
positron emission tomography. Direct nucleophilic fluorination of aromatic rings
with [(18) F]fluoride is limited to activated substrates, restricting the
application of this approach. Inspired by transition metal-mediated
transformations, a fluorine-18 synthon was prepared to supplement the
radiolabelling methods available for molecules unsuitable for direct labelling. 2
Bromo-6-[(18) F]fluoropyridine (denoted [(18) F]1) was prepared in high yield,
and palladium-mediated cross-coupling reactions were exemplified. High
incorporation of fluoride and efficient cross-coupling reactions demonstrate that
compound [(18) F]1 holds promise as a new synthon for construction of fluorine-18
labelled molecules via transition metal-mediated reactions.
PMID- 24347379
TI - Care, compounded: researchers delve into reasons behind pregnancy-associated
breast cancer.
PMID- 24347382
TI - Progression-free survival: does a correlation with survival justify its role as a
surrogate clinical endpoint?
PMID- 24347383
TI - Breast cancer presentation and diagnostic delays in young women.
AB - BACKGROUND: Young women may experience delays in diagnosis of breast cancer, and
these delays may contribute to poorer outcomes. METHODS: In a prospective,
multicenter cohort study, women recently diagnosed with breast cancer at age <=40
years were surveyed regarding their initial signs or symptoms of cancer and
delays in diagnosis. Self delay was defined as >=90 days between the first sign
or symptom and a patient's first visit to consult a health care provider. Care
delay was defined as >=90 days between that first visit and the diagnosis of
breast cancer. In a medical record review, tumor characteristics were assessed,
including disease stage. Univariate and multivariate models were used to assess
for predictors of self delay, care delay, and advanced stage in the self-detected
subset. RESULTS: In 585 eligible participants, the first sign or symptom of
cancer was a self-detected breast abnormality for 80%, a clinical breast
examination abnormality for 6%, an imaging abnormality for 12%, and a systemic
symptom for 1%. Among women with self-detected cancers, 17% reported a self
delay, and 12% reported a care delay. Self delays were associated with poorer
financial status (P = 0.01). Among young women with self-detected breast cancers,
care delay was associated at trend level (P = .06) with higher stage in
multivariate modeling. CONCLUSIONS: Most young women detect their own breast
cancers, and most do not experience long delays before diagnosis. Women with
fewer financial resources are more likely to delay seeking medical attention for
a self-detected breast abnormality.
PMID- 24347384
TI - Progression-free survival as a surrogate endpoint of overall survival in patients
with metastatic renal cell carcinoma.
AB - BACKGROUND: The current study was conducted to investigate the dependence between
progression-free survival (PFS) and overall survival (OS) in patients with
metastatic renal cell carcinoma (mRCC) and to explore whether PFS can be used as
an intermediate endpoint of OS in this patient population. METHODS: A total of
1381 patients from 2 prospective phase 3 trials (Cancer and Leukemia Group B
[CALGB] 90206 and AVOREN) of interferon-alpha with or without bevacizumab were
analyzed. Both trials recruited previously untreated patients with clear cell
mRCC with an Eastern Cooperative Oncology Group performance status of 0 to 2;
adequate bone marrow, hepatic, cardiac, and renal function; and controlled blood
pressure. The CALGB study served as the training data set, and the AVOREN study
served as the testing data set. The dependence between PFS and OS was
investigated using the Kendall tau for bivariate time-to-event endpoints.
RESULTS: In the training data set, the median OS times among patients who
experienced progressive disease at 3 months or 6 months were 6 months and 8
months, respectively, compared with 25 months and 30 months, respectively, (P <
.001) in patients who did not develop disease progress. The adjusted hazard
ratios (HR) were 2.6 (P < .0001) and 2.8 (P < .0001), respectively, for patients
who did and did not progress at 3 months or 6 months. The dependence between PFS
and OS was 0.53. These associations were confirmed in the testing data set.
CONCLUSIONS: In patients with mRCC who were treated with interferon-alpha with or
without bevacizumab, the PFS at 3 months and 6 months was found to be predictive
of OS. A high dependence between PFS and OS was observed, suggesting that PFS may
be used as a surrogate endpoint for OS. Although this is a novel observation for
RCC, these findings require validation in patients with mRCC who are treated with
other targeted agents.
PMID- 24347385
TI - Otolaryngologist-assisted fluoroscopic-guided nasogastric tube placement in the
postoperative laryngectomy patient.
PMID- 24347386
TI - Ontogenetic study of allometric variation in Homo and Pan mandibles.
AB - Investigating ontogenetic variation and allometry in the mandible can provide
valuable insight and aid in addressing questions related to the ontogeny of the
skull. Here, patterns of ontogenetic shape change and allometric trajectories
were examined in the mandible of 187 sub-adult and adult humans, bonobos, and
chimpanzees. Procrustes-based geometric morphometrics was employed to quantify
and analyze mandibular form. Thirty three-dimensional landmarks were used to
capture the overall morphology of the mandible, and the landmarks were analyzed
as a whole and subdivided into separate anterior and posterior units. Principal
component analyses in Procrustes shape-space and form-space, and multivariate
regressions were used to examine patterns of ontogenetic and allometric shape
change. Results suggest that humans are distinct from Pan both in their
mandibular morphology, particularly in the anterior-alveolar region, and
direction of allometric trajectory. Chimpanzees and bonobos have parallel
ontogenetic trajectories, but also show differences in mandibular shape. Species
specific features and adult mandibular shape are established before or by the
eruption of the deciduous dentition. This suggests that developmental processes
prior to deciduous teeth eruption have a stronger effect establishing taxa
specific phenotypes than later postnatal effects. This additionally implies that
divergent trajectories between Pan and Homo do not contribute much to the adult
mandibular shape after deciduous teeth eruption. Separate analyses of the
anterior-alveolar region and ascending ramus show that these regions are semi
independent in their developmental pattern of shape change and allometry. This
implies that allometric variation and ontogenetic shape change in the hominoid
mandible is decoupled.
PMID- 24347387
TI - Early retirement and non-employment after breast cancer.
AB - OBJECTIVE: This study examined whether workplace support, sociodemographic
factors and co-morbidity are associated with early retirement or non-employment
due to other reasons among breast cancer survivors. We also compared quality of
life and chronic symptoms (pain, fatigue, anxiety and depression) among employed,
retired and other non-employed breast cancer survivors. METHODS: We identified
breast cancer survivors diagnosed between 1997 and 2002 from either a hospital or
a cancer registry in Denmark, Finland, Iceland and Norway (NOCWO study). All
patients had been treated with curative intent. Information on employment, co
morbidity and support was collected via a questionnaire. The sample included 1111
working-aged cancer-free survivors who had been employed at the time of
diagnosis. We used multinomial logistic regression models to analyse the
association of various determinants with early retirement and other non
employment (due to unemployment, subsidized employment or being a homemaker).
RESULTS: Low education, low physical quality of life, co-morbidity and pain were
associated with both early retirement and other non-employment after cancer.
Other non-employed survivors also rated their mental quality of life as lower and
experienced anxiety and fatigue more often than all the other survivors.
Moreover, they reported a lower level of supervisor support after their diagnosis
than the employed survivors. Retired survivors more often reported weak support
from colleagues. CONCLUSIONS: Differences in ill health and functional status
between various groups of non-employed cancer survivors need to be considered
when planning policy measures for improving the labour market participation of
this population and preventing their early withdrawal from working life.
PMID- 24347388
TI - Phosphorylation of PRAS40-Thr246 involved in renal lipid accumulation of
diabetes.
AB - Lipid accumulation of kidney is a threat to renal physiological function of
diabetes. The previous studies on diabetic nephropathy have demonstrated that
activated Akt was involved in renal lipogenesis through enhancing transcription
factor SREBP-1. PRAS40 is one of the downstream targets of activated Akt that was
reported to involve in lipid metabolism in hepatic cells. However, it is still
not clear whether PRAS40 is also involved in the renal lipogenesis of diabetes.
Our study revealed that phosphorylation of PRAS40-Thr246 known as inactivated
style increased in renal tubular cells of diabetic rats accompanied with over
expression of phospho-Akt, SREBP-1, and ADRP. In addition, in vitro experiment
also found that high glucose enhanced expression of phospho-PRAS40-Thr246
followed by increased SREBP-1 and lipid droplets in HKC cells. After treated with
LY294002, high glucose-induced HKC cells showed decreased phospho-PRAS40-Thr246,
phospho-Akt-Ser473, and SREBP-1. Furthermore, wild type PRAS40 vector-caused
increased phospho-PRAS40-Thr246 exaggerated lipid deposits in high glucose
treated HKC cells, which was effectively prevented in cells transfected with
mutant PRAS40 vector (T246A). These above data suggested that phosphorylation of
PRAS40-Thr246 mediated abnormal lipid metabolism in kidney of diabetes and might
be the potential target for treating lipogenesis of diabetic nephropathy.
PMID- 24347393
TI - Juvenile play experience does not affect nicotine sensitization and voluntary
consumption of nicotine in adult rats.
AB - Juvenile play experiences promote behavioral flexibility in rats. If other early
positive experiences, such as tactile stimulation, are given prior to exposure to
psychostimulants, the behavioral response to the drug is attenuated. The
objective of the present study was to determine if the experience of juvenile
play behavior would attenuate the response to nicotine. Two experiments were
conducted: (1) behavioral sensitization to nicotine exposure, and (2) voluntary
consumption of nicotine. For both experiments, rats were reared either with three
same-sex peers (play group) or one adult (no play group) during their juvenile
period. Then, as adults, half of each group was exposed to repeated injections of
nicotine and the other half to saline. Prior play experience had no effect on
behavioral sensitization or on voluntary consumption of nicotine. It remains to
be determined whether juvenile experience with play influences the rewarding
properties of nicotine in social contexts as adults.
PMID- 24347394
TI - High--valent technetium chemistry-new opportunities for radiopharmaceutical
developments.
AB - The rich coordination chemistry of (99m) Tc distinguishes this radiometal from
other radiolabels applied for single-photon emission computed tomography (SPECT)
or positron emission tomography (PET). This potential should be used to create
novel opportunities for the development of effective imaging probes. In this
context, the field of high-valent technetium chemistry has received much
interest. It has been shown that fac-{(99m) TcO3 }(+) complexes are potential new
synthons for radiopharmaceutical developments, due to their unique
physicochemical properties and unprecedented reactivity. In this article, recent
developments and the 'state of the art' in this field of technetium chemistry
will be reviewed comprehensively.
PMID- 24347395
TI - Sarcoglycan complex in human normal and pathological prostatic tissue: an
immunohistochemical and RT-PCR study.
AB - The sarcoglycan complex is a trans-membrane system playing a key role in mechano
signaling the connection from the cytoskeleton to the extracellular matrix. While
b-, d-, and e-sarcoglycans are widely distributed, g- and a-sarcoglycans are
expressed exclusively in skeletal and cardiac muscle. Insufficient data are
available on the distribution of sarcoglycans in nonmuscular tissue. In the
present study, we used immunohistochemical and RT-PCR techniques to study the
sarcoglycans also in normal human glandular tissue, a type of tissue never
studied in relation to the sarcoglycan complex, with the aim of verifying the
real wider distribution of this complex. To understand the role of sarcoglycans,
we tested specimens collected from patients affected by benign prostatic
hyperplasia and adenocarcinoma. For the first time, our results showed that all
sarcoglycans are detectable in normal samples both in epithelial and in
myoepithelial cells; in pathological prostate, sarcoglycans appeared severely
reduced in number or were absent. These data demonstrated that all sarcoglycans
have a wider distribution suggesting a new unknown role for these proteins. The
decreased number of sarcoglycans, containing cadherin domain homologs in samples
of prostate affected by hyperplasia, and the absence of proteins in prostate
biopsies, in cases affected by adenocarcinoma, could be responsible for the loss
of adhesion between epithelial cells, which in turn facilitates the progression
of benign tumors and the invasive potential of malignant tumors.
PMID- 24347396
TI - Application of polyglycerol coating to plasmid DNA lipoplex for the evasion of
the accelerated blood clearance phenomenon in nucleic acid delivery.
AB - Cationic liposomes (CLs) have shown promise as nonviral delivery systems. To
achieve in vivo stability and long circulation, most liposomes are modified with
hydrophilic polymer polyethylene glycol (PEG). However, we have reported that
repeated administration of PEG-coated CLs containing plasmid DNA (pDNA; PEGylated
lipoplexes) induces what is referred to as "the accelerated blood clearance (ABC)
phenomenon" and, consequently, subsequently administered lipoplexes lose their
prolonged circulation characteristics. Anti-PEG IgM produced in response to the
first dose of PEG-coated pDNA-lipoplexes (PEG-DCL) has proven to be a major cause
of the ABC phenomenon. In this study, to evade and/or attenuate this unexpected
immune response, we modified the surface of a lipoplex with polyglycerol (PG)
derived lipid. The PG-coated pDNA-lipoplex (PG-DCL) attenuated the production of
anti-polymer IgM, whereas PEG-coated pDNA-lipoplex (PEG-DCL) did not. In
addition, a second dose of PG-DCL maintained the accumulation level in the tumor
tissue of a tumor-bearing mouse model, comparable to that of the first dose,
whereas the tumor accumulation level of a second dose of PEG-DCL was
significantly compromised, compared with the first dose of PEG-DCL. Our results
indicate that surface modification of lipoplex with PG represents a viable means
for the attenuation, and/or evasion, of the ABC phenomenon that is encountered
upon repeated administrations of nucleic acids containing PEG-coated
nanocarriers.
PMID- 24347397
TI - Dual-scaled porous nitrocellulose membranes with underwater superoleophobicity
for highly efficient oil/water separation.
AB - Large-area dual-scaled porous nitrocellulose (p-NC) membranes are fabricated by a
facile, inexpensive and scalable perforating approach. These p-NC membranes show
stable superhydrophilicity in air and underwater superoleophobicity. The p-NC
membranes with intrinsic nanopores and array of microscale perforated pores could
selectively and efficiently separate water from various oil/water mixtures with
high efficiency (>99%) rapidly.
PMID- 24347398
TI - Diastereotopic splitting in the 13C NMR spectra of sulfur homofullerenes and
methanofullerenes with chiral fragments.
AB - Using gauge-invariant atomic orbital PBE/3zeta quantum chemistry approach, (13)C
NMR chemical shifts and diastereotopic splittings of sp(2) fullerenyl carbons of
a number of sulfur homofullerenes and methanofullerenes have been predicted and
discussed. An anisochrony of fullerene carbons is caused by a chiral center of
attached moieties. Clearly distinguishable diastereotopic pairs (from 8 to 11) of
fullerenyl carbons of homofullerenes were observed. Unambiguous assignments of
(13)C NMR chemical shifts were performed, and diastereotopic splittings of
methanofullerenes were observed for alpha, beta and gamma to a functionalization
site.
PMID- 24347399
TI - 13C and 15N CP/MAS, 1H-15N SCT CP/MAS and FTIR spectroscopy as tools for
qualitative detection of the presence of zwitterionic and non-ionic forms of ansa
macrolide 3-formylrifamycin SV and its derivatives in solid state.
AB - (13)C, (15)N CP/MAS, including (1)H-(13)C and (1)H-(15)N short contact time
CP/MAS experiments, and FTIR methods were applied for detailed structural
characterization of ansa-macrolides as 3-formylrifamycin SV (1) and its
derivatives (2-6) in crystal and in powder forms. Although HPLC chromatograms for
2/CH3 OH and 2/CH3 CCl3 were the same for rifampicin crystals dissolved in
respective solvents, the UV-vis data recorded for them were different in 300-375
nm region. Detailed solid state (13)C and (15)N CP/MAS NMR and FTIR studies
revealed that rifampicin (2), in contrast to 3-formylrifamycin SV (1) and its
amino derivatives (3-6), can occur in pure non-ionic or zwitterionic forms in
crystal and in pure these forms or a mixture of them in a powder. Multinuclear
CP/MAS and FTIR studies demonstrated also that 3-6 derivatives were present
exclusively in pure zwitterionic forms, both in powder and in crystal. On the
basis of the solid state NMR and FTIR studies, two conformers of 3
formylrifamycin SV were detected in powder form due to the different orientations
of carbonyl group of amide moiety. The PM6 molecular modeling at the semi
empirical level of theory, allowed visualization the most energetically favorable
non-ionic and zwitterionic forms of 1-6 antibiotics, strongly stabilized via
intramolecular H-bonds. FTIR studies indicated that the originally adopted forms
of these type antibiotics in crystal or in powder are stable in standard
laboratory conditions in time. The results presented point to the fact that
because of a possible presence of two forms of rifampicin (compound 2),
quantification of the content of this antibiotic in relevant pharmaceuticals
needs caution.
PMID- 24347400
TI - Structure elucidation and NMR assignments of two unusual xanthones from
Lomatogonium carinthiacum (Wulf) Reichb.
AB - Two new unusual xanthones, 5-O-beta-d-glucopyranosyl-1,3,8-trihydroxy-5,6,7,8
tetrahydroxanthone (1) and 1,3,5,8-tetrahydroxy-5,6,7,8-tetrahydroxanthone (2),
were isolated from Lomatogonium carinthiacum (Wulf) Reichb. Their structures were
elucidated on the basis of spectroscopic methods including UV, IR, ESI-MS, 1D
NMR, and 2D NMR.
PMID- 24347401
TI - They still grieve-a nationwide follow-up of young adults 2-9 years after losing a
sibling to cancer.
AB - OBJECTIVES: The aims of this study were to assess the prevalence of unresolved
grief in bereaved young adult siblings and examine possible contributing factors.
METHODS: The study was a Swedish population-based study of young adults who had
lost a brother or sister to cancer, 2-9 years earlier. Of 240 eligible siblings,
174 (73%) completed a study-specific questionnaire. This study focused on whether
the respondents had worked through their grief over the sibling's death and to
what extent. RESULTS: A majority (54%) of siblings stated that they had worked
through their grief either 'not at all' or 'to some extent' at the time of
investigation. In multiple regression analyses with unresolved grief as the
dependent variable, 21% of the variance was explained by lack of social support
and shorter time since loss. CONCLUSION: The majority of bereaved young adults
had not worked through their grief over the sibling's death. A small group of
siblings reported that they had not worked through their grief at all, which may
be an indicator of prolonged grief. Lack of social support and more recent loss
were associated with not having worked through the grief over the sibling's
death.
PMID- 24347402
TI - Identification of risk factors for an unsuccessful transition from pediatric to
adult sickle cell disease care.
AB - BACKGROUND: A successful transition from pediatric to adult sickle cell disease
(SCD) care is paramount to continued improvements in survival. In order to
enhance transition success, our pediatric SCD transition process was modified to
include combined adult and pediatric provider clinics that incorporated
participation by our local SCD community-based organization. All children ages 16
and over participated in this newly-formed transition program. PROCEDURE: After 5
years of implementation of the modified SCD transition program, we
retrospectively studied clinical and non-clinical risk factors for an
unsuccessful transition. Risk factor categories studied included patient
demographics, transition clinic attendance, and disease severity. RESULTS: Thirty
two percent of patients did not transition successfully. Demographic factors such
as gender, race, and type of insurance did not influence transition outcome,
although travel distance to the adult SCD center was an identifiable risk factor
for an unsuccessful transition. While transition clinic attendance rate did not
affect transition outcomes, older age at first modified combined transition
clinic visit was a significant risk factor for lack of transition. Patients with
clinical markers of milder disease severity (SC and Sbeta(+) genotypes and no
chronic transfusion therapy) were at higher risk for an unsuccessful transition
than patients with severe disease. CONCLUSIONS: We have identified several risk
factors for lack of transition success which will allow us to modify our
transition efforts going forward to capture this highest risk subset.
PMID- 24347403
TI - In reference to "is nasopharyngoscopy necessary in adult-onset otitis media with
effusion?".
PMID- 24347404
TI - Characterization of a new model of thromboembolic stroke in C57 black/6J mice.
AB - This study characterizes a new model of thromboembolic stroke of the middle
cerebral artery in C57 black/6J mice, thus offering an opportunity to use the
model for studying ischemic stroke in transgenic mice. Thromboembolic stroke was
induced by local injection of either 1.5 or 3.0 UI of thrombin directly into the
right MCA of C57 black/6J mice. Cerebral blood flow (CBF) velocity was measured
continuously by laser Doppler flowmetry, which allowed documentation of both MCA
occlusion and of spontaneous recanalization. After 24 h, all animals were
euthanized. Cryosections were cut at 400-MUm intervals and silver stained with
the high-contrast method for volumetric assessment of infarct size. Interleukin
(IL)-6, tumor necrosis factor-alpha (TNF-alpha), caspase-3 and hsp 70 protein
levels were investigated by immunofluorescence. Thrombin injection resulted in
clot formation in all animals. Cortical infarction occurred in 63% of the mice
while 37% had a spontaneous MCA recanalization during the first 20 min following
thrombin injection. In cases of successful MCA occlusion with consequent
infarction, the clot was stable up to 2 h after formation. Subsequently, 20%
recanalized spontaneously. Infarctions were restricted to the cortex with a mean
lesion volume of 36 +/- 5 for 1.5 UI and 56 +/- 8 for 3.0 UI thrombin. Protein
levels of IL-6, TNF-alpha, caspase-3, and hsp 70 were significantly increased
after MCAO. The results demonstrate that the mouse thromboembolic stroke model
produces cortical infarctions of consistent size in C57 black/6J mice, which is
dependent upon the amount of thrombin used for clot formation. Spontaneous MCA
recanalization occurs after 2 h of ischemia in 20% of mice. Thus, the
thromboembolic model is an applicable stroke model for C57 black/6J mice, which
mimics many of the features of human stroke, including spontaneous
recanalization. However, strain differences between Swiss and C57 black/6J mice
must be taken into account when using the model.
PMID- 24347406
TI - Physical activity disparities in heterosexual and sexual minority youth ages 12
22 years old: roles of childhood gender nonconformity and athletic self-esteem.
AB - BACKGROUND: Physical activity is an important health determinant. Little is known
about sexual orientation differences in physical activity and their psychosocial
determinants. PURPOSE: The aim of this study is to examine adolescent and young
adult hours/week of moderate/vigorous physical activity (MVPA) and team sports
participation by sexual orientation and investigate contributions of gender
nonconformity and low athletic self-esteem to possible sexual orientation
differences. METHODS: Analysis of data from 5,272 males and 7,507 females from
1999 to 2005 waves of the US Growing Up Today Study (ages 12-22 years). RESULTS:
Sexual minorities (i.e., lesbian, gay, bisexual, mostly heterosexual) reported
1.21-2.62 h/week less MVPA (p < 0.01) and were 46-76 % less likely to participate
in team sports than same-gender heterosexuals. Gender nonconformity and athletic
self-esteem accounted for 46-100 % of sexual orientation MVPA differences.
CONCLUSIONS: Physical activity contexts should be modified to welcome sexual
minority males and females. Targeting intolerance of gender nonconformity and
fostering athletic self-esteem may mitigate sexual orientation MVPA disparities.
PMID- 24347407
TI - Psychosocial mediators of two community-based physical activity programs.
AB - BACKGROUND: Previous findings are inconclusive regarding the mediators of
physical activity behavior change. PURPOSE: To test self-efficacy and social
support as mediators of Active Choices, a telephone-delivered physical activity
intervention, and Active Living Every Day, a group-based physical activity
intervention, implemented with midlife and older adults in community settings.
METHODS: MacKinnon's product of coefficients was used to examine social support
and self-efficacy as mediators of change in physical activity. The proportion of
the total effect mediated was calculated. Each model controlled for age, gender,
race (white vs. non-white), body mass index (BMI), and education (high school
graduate or less vs. at least some college). RESULTS: Increases in self-efficacy
mediated increases in physical activity among Active Choices (n = 709) and Active
Living Every Day (n = 849) participants. For Active Living Every Day, increases
in social support also mediated increases in physical activity in single mediator
models. CONCLUSIONS: Increasing self-efficacy and social support may help
increase physical activity levels in older adults.
PMID- 24347405
TI - Sexual orientation and gender differences in markers of inflammation and immune
functioning.
AB - BACKGROUND: Sexual minorities have documented elevated risk factors that can lead
to inflammation and poor immune functioning. PURPOSE: This study aims to
investigate disparities in C-reactive protein (CRP) and Epstein-Barr virus (EBV)
by gender and sexual orientation. METHODS: We used the National Longitudinal
Study of Adolescent Health to examine disparities in CRP (N = 11,462) and EBV (N
= 11,812). RESULTS: Among heterosexuals, women had higher levels of CRP and EBV
than men. However, sexual minority men had higher levels of CRP and EBV than
heterosexual men and sexual minority women. Lesbians had lower levels of CRP than
heterosexual women. CONCLUSIONS: Gender differences in CRP and EBV found between
men and women who identify as 100 % heterosexual were reversed among sexual
minorities and not explained by known risk factors (e.g., victimization, alcohol
and tobacco use, and body mass index). More nuanced approaches to addressing
gender differences in sexual orientation health disparities that include measures
of gender nonconformity and minority stress are needed.
PMID- 24347408
TI - A comprehensive study of named entity recognition in Chinese clinical text.
AB - OBJECTIVE: Named entity recognition (NER) is one of the fundamental tasks in
natural language processing. In the medical domain, there have been a number of
studies on NER in English clinical notes; however, very limited NER research has
been carried out on clinical notes written in Chinese. The goal of this study was
to systematically investigate features and machine learning algorithms for NER in
Chinese clinical text. MATERIALS AND METHODS: We randomly selected 400 admission
notes and 400 discharge summaries from Peking Union Medical College Hospital in
China. For each note, four types of entity-clinical problems, procedures,
laboratory test, and medications-were annotated according to a predefined
guideline. Two-thirds of the 400 notes were used to train the NER systems and one
third for testing. We investigated the effects of different types of feature
including bag-of-characters, word segmentation, part-of-speech, and section
information, and different machine learning algorithms including conditional
random fields (CRF), support vector machines (SVM), maximum entropy (ME), and
structural SVM (SSVM) on the Chinese clinical NER task. All classifiers were
trained on the training dataset and evaluated on the test set, and micro-averaged
precision, recall, and F-measure were reported. RESULTS: Our evaluation on the
independent test set showed that most types of feature were beneficial to Chinese
NER systems, although the improvements were limited. The system achieved the
highest performance by combining word segmentation and section information,
indicating that these two types of feature complement each other. When the same
types of optimized feature were used, CRF and SSVM outperformed SVM and ME. More
specifically, SSVM achieved the highest performance of the four algorithms, with
F-measures of 93.51% and 90.01% for admission notes and discharge summaries,
respectively.
PMID- 24347409
TI - [Management of dislocated radial head fractures with biodegradable implants].
AB - BACKGROUND: The Mason classification is used for radial head fractures. Mason
type I fractures are managed by a functional conservative treatment of no loading
for six weeks. Mason II fractures with a displacement greater than 10 degrees or
a depression of greater than 2 millimeters are treated with open reduction and
use of biodegradable implants constructed of polylactide. These implants have the
advantage of maintaining the joint surface by placement beneath the surface of
the articular cartilage. Furthermore, the implants can be placed from various
positions through the articular surface and are therefore more versatile than
other modes of open reduction. METHOD: The OP technique in Mason II radial head
fracture is demonstrated in a video for the example of a 31-year-old male
patient. RESULTS: 35 patients were treated using the new polylactide pins
(Polypin(r)). Average follow-up for 34 patients was 38 months. 31 patients with
Mason type II fractures presented with a score of 96 out of 100 using the Broberg
Morrey score. CT scans were performed after 18 and 24 months in all patients. One
first degree asymptomatic osteolysis was observed at 18 months which was reduced
at 24 months. Two years later the pins were not visible on conventional X-rays.
CT scans at 5 years revealed the implants to be in various levels of resorption
and bony regrowth. CONCLUSION: Dislocated radial head fractures can be treated
with good results with biodegradable implants.
PMID- 24347410
TI - [Editorial for the Journal of Orthopaedic and Trauma Surgery].
PMID- 24347411
TI - [Medium- to long-term follow-up after anterior cruciate ligament rupture and
repair in healing response technique].
AB - BACKGROUND: Healing response (HR) is an all-arthroscopic technique for treatment
of acute proximal anterior cruciate ligament (ACL) tears within 6 weeks after
injury. By means of arthroscopically controlled microfracture holes in the native
femoral attachment and perforations of the ACL itself the exit of stem cells and
growth factors is induced and the ligament can heal into its native attachment
zone. The purpose of the study was to document medium- to long-term results after
5 years or longer following the healing response (HR) procedure. The aim of our
study was to show that HR is a treatment option for acute proximal ACL tears.
MATERIAL AND METHODS: Between 2004 and 2007 126 patients were treated in healing
response technique in our hospital. Patients with a complete proximal ACL tear
and operation within 6 weeks of initial injury were included in this study.
Patients who had complex knee injuries with multidirectional instability, ACL
rerupture, contralateral ACL reconstruction, contralateral ACL rupture or knee
replacement and cartilage repair procedures (AMIC, MACT, OATS) were excluded. 43
(23 women/20 men; mean age at time of surgery 36.6 years +/- 11.6; range: 16 to
66 years) of 89 eligible patients received clinical follow-up up to 8 years after
surgery (mean: 6.3 years). Lysholm score, Tegner activity score, a modified IKDC
2000 knee examination form and an individually created questionnaire were used
for evaluation. Furthermore, range of motion, muscle circumference of the lower
limb and the anterior tibial translation were measured with a KT-1000
arthrometerTM (MEDmetric(r) Corporation, San Diego, USA). RESULTS: 15.1 % of all
patients showed a primary insufficiency after HR. 24.6 % of the 126 patients
required subsequent ACL reconstruction up to the time of data collection. The 43
patients who received clinical follow-up showed a mean Lysholm score of 92 +/-
8.9 points. 72 % reached their original level of activity in the Tegner activity
score. According to the IKDC evaluation system 90.7 % of all patients were grade
A. 93 % did not show muscles atrophies of the lower limb. There were no
limitations in range of motion. Mean side-to-side difference in the KT-1000
manual-maximum displacement test measurements was 1.3 mm +/- 1.6 mm. 97.7 %
patients had a normal or nearly normal knee function and 86 % rated the overall
treatment as good to very good. CONCLUSION: Patients with good clinical results 6
to 12 weeks after HR show even in the medium- to long-term follow-up good
clinical outcomes as well as objective stability. In selected cases HR is an
alternative treatment option for acute, proximal ACL ruptures. When indicating an
HR procedure, it should be taken into consideration that up to 15 % of all
patients could have a primary insufficiency.
PMID- 24347412
TI - [Intraoperative damage to the medial collateral ligament (MCL) - what is to be
done?].
AB - BACKGROUND: Intraoperative damage to the medial collateral ligament is a rather
rare condition given only scant attention in the literature. Observing
international medical journals (over the recent years), one finds very few case
histories. What is more, these case histories vary significantly with regards to
their approaches to the problem at hand. MATERIAL AND METHODS: This survey lists
essential publications and case histories in question and - following their
analysis and in light of the fairly low number of respective cases - attempts to
create a 'treatment algorithm'. RESULTS: Approaches to treatment vary
considerably throughout the medical literature. Reasons are the localisation of
the actual damage, pertaining to the medial collateral ligament as well as
surgeons' aptitudes and preferences with regards to hinged or constraint
implants. Eventually, there are five different treatment options: (i) solely
conservative treatment by means of an orthesis; (ii) primary reconstruction of
the medial collateral ligament; (iii) medial collateral ligament augmentation;
(iv) inlay elevation and lateral release procedure; and (v) a higher degree of
coupling regarding the TKA. CONCLUSION: It is strongly advised to refrain from
conducting a release at the femoral origin of the medial collateral ligament. In
stages, a tibial release should be carried out strictly subperiostally. A high
expenditure of energy during tension examination needs to be utterly avoided.
Reconstruction of the femoral origin/insertion can be carried out rather safely,
while reconstruction of the tibial origin/insertion is more complicated due to
the more complex anatomic line-up/constellation. Likewise, the reconstruction of
the median ligament portion is considerably more difficult; in this case, the
application of a primary suture or augmentation by use of the semitendinosus or
quadriceps tendon are recommended. In addition, the temporary application of an
orthesis is recommended regardless. In any case, a higher degree of coupling
should be considered as a fallback. Introduced is an algorithm which
differentiates the ligament damage location.
PMID- 24347413
TI - [Characteristics in treatment of the hip in patients with Down syndrome].
AB - BACKGROUND: The treatment of hip instability in patients with Down syndrome is
challenging. We have performed different pelvic osteotomies and corrections at
the proximal femur for this indication. This retrospective study was conducted to
evaluate the clinical and radiological outcome of each intervention. MATERIAL AND
METHODS: All in all, 166 patients with Down syndrome were treated at our
orthopaedic department in the observation period. Problems related to the hip
joint were diagnosed in 63 of those patients. Only patients who underwent surgery
were included in this study. The charts and X-rays of these 31 patients were
evaluated with respect to the following parameters: incidence of the hip problem,
concomitant diseases, temporal progress, kind of operation method and date,
duration of stay in the hospital, after-care, follow-on surgery related to
complications, AC angle, CE angle, ACM angle, CCD angle, index of migration
according to Reimers, classification of Bauer and Kerschbauer and general
morphology of the femoral head. The group was compared with an age-matched group
of 21 patients with hip dysplasia. Those patients underwent the same sort of
operation in the same year. RESULTS: In the Morbus Down group, we performed
surgery for preservation of the hip in 49 cases. This included 13 osteotomies
according to Chiari, 11 triple osteotomies according to Tonnis, 10 corrections by
femoral varus derotation osteotomy, 8 pelvic osteotomies according to Pemberton,
5 pelvic osteotomies according to Salter and 2 open reductions of the hip. With
respect to the moment of surgery, we detected three peaks of age. There was no
difference in course of disease and quantity of complications between the groups.
Satisfactory results concerning clinical and radiological outcome were achieved
predominantly by complete redirectional acetabular osteotomies. Half of the
patients who were solely treated by femoral varus derotation osteotomy needed
follow-on surgery in the form of pelvic osteotomy. Comparison of preoperative and
postoperative range of motion of the hip joint between groups detected capsular
insufficiency, increased ligamentous laxity and muscular hypotonia in patients
with Down syndrome. Comparison of pelvic radiographs demonstrated significant
improvement concerning measured angles in both groups. Preoperative values with
respect to AC angle and CE angle were demonstrated to be lower in the hip
dysplasia group (p < 0.01); whereas values for ACM angle were comparable between
groups. CONCLUSION: Hypermobility and secondary dislocation of the hip joint is a
common problem in patients with Down syndrome, which often requires surgical
intervention at an early stage. According to our data and clinical results we
suggest a complete redirectional acetabular osteotomy in combination with
capsular plication for treatment of this challenging condition.
PMID- 24347414
TI - [Treatment of septic arthritis of the hip in children and adolescents].
AB - GOAL: Irrigation of the hip joint by hip arthrotomy represents the standard
treatment for septic arthritis of the hip in childhood and adolescence.
Arthroscopic lavages for treating a septic knee, elbow, ankle and glenohumeral
joints are well established, but have only reached little acceptance in the
therapy of septic hip arthritis in children. The goal of this study is to
evaluate the advantages of the minimally invasive arthroscopic high-volume lavage
for septic hip arthritis with regards to treatment safety and complication
frequency. PATIENTS AND METHODS: 20 children aged 6.4 years on average (2-14
years) with obvious signs of septic arthritis of the hip proven clinically and by
blood tests were arthroscopically treated in a 2-portal technique. In a prone
position on a standard table the patient had the arthroscopic lavage procedure
followed by insertion of a Redon tube. In all cases a histological sample and a
bacterial swab were taken. A traction table was not used. In three children there
was a stage I according to Stutz and Gachter, in thirteen a stage II and in four
patients a stage III. Because of a concomitant femoral neck osteomyelitis in
three cases and an osteomyelitis of the os pubis in a single patient, PMMA mini
chains were locally administered. The histological samples were reported as
purulent in 16 and as non-specific synovitis in four patients. In ten children a
positive bacterial result was given, with Staphylococcus aureus found in 7 cases
and single cases with Meningococci, Salmonella and Staphylococcus warneri. All
patients received an intravenous antibiotic treatment for 14 days followed by
four weeks of oral antibiotics. RESULTS: 16 out of 20 children were sufficiently
treated by one single arthroscopic lavage. In three cases with additional
osteomyelitis a secondary procedure was needed for removal of the antibiotic
chain. During follow-up after an average of 2.9 years 19 of 20 children
demonstrated a free range of hip joint motion and a full sporting activity
without any restrictions. One girl with stage III arthritis and a preoperative
duration of symptoms of seven days developed a femoral head necrosis and
chondrolysis with hip joint subluxation. The other 19 patients regained an
excellent Harris hip score at follow-up, whereas the girl only produced moderate
score values. So, 19 children had an unrestricted function of their hips on the
same activity level as before. CONCLUSION: The 2-portal hip arthroscopy with high
volume lavage represents a safe and minimally invasive method in order to
successfully treat septic arthritis of the hip and concomitant femoral neck
osteomyelitis in children and adolescents. This technique leads to a very low
morbidity offering all advantages of arthroscopic procedures. The use of
cannulated instruments through well established safe portals makes this
arthroscopic lavage procedure a simple and easily adoptable technique.
PMID- 24347415
TI - [Fibromyalgia syndrome - updated s3 guidelines].
AB - Patients with chronic widespread pain often present with musculo-skeletal pain
and therefore often initially contact an orthopaedist. For these patients
fibromyalgia syndrome is an important differential diagnosis. Recommendations for
the diagnosis of and therapy for fibromyalgia syndrome based on the recent German
S3 guidelines for fibromyalgia syndrome (AWMF registration number 041/004) are
outlined in this paper. These guidelines were developed under the coordination of
the German interdisciplinary association for pain management DIVS and two patient
support groups. The history of a typical symptom complex and the exclusion of
relevant somatic causes for the pain are epecially relevant for the diagnosis of
fibromyalgia syndrome. Besides the exclusion of relevant orthopaedic causes for
the pain, psycho-social aspects should always be evaluated. According to the
modified ACR criteria 2010, chronic widespread pain and accompanying sleep
disturbances and a physical as well as mental state of exhaustion lead to the
diagnosis of fibromyalgia syndrome. It is not mandatory to check tender points
(ACR 1990 criteria). A graduated treatment approach depending on the severity
level of the fibromyalgia syndrome in the individual patient is recommended.
Active treatment options (aerobic training, meditative movement therapies,
strength training) should be preferred to any drug therapy in the long-term
treatment of fibromyalgia. If indicated, amitryptiline or duloxetine may be used
to treat accompanying depressive or generalised anxiety disorder. Muscle relaxant
medication, non-steroidal anti-inflammatory drugs and strong opioids should be
avoided. The multimodal pain therapy considering all psycho-social aspects is a
promising treatment option for fibromyalgia syndrome of moderate to high
severity.
PMID- 24347416
TI - [Logbook of learning targets for special educational skills in orthopaedic and
trauma surgery for undergraduate medical training].
AB - INTRODUCTION: The changes in medical licensing regulations introduced in Germany
in 2012 require the development of specific catalogues, termed logbooks, that
define the practical skills medical students should acquire in different
specialties. In conjunction with another change in medical education, which
allows medical students to freely select any German university hospital or
academic teaching hospital for their one-year internship, these catalogues are a
prerequisite for ensuring comparable training standards throughout Germany. The
German licensing regulations provide no details regarding the contents or form of
the logbooks but only mention a "training programme" in very general terms. A
logbook is commonly understood to define clear learning objectives to be
accomplished during a specified interval (4 months). The conference of German
medical faculties proposed a basic logbook for compulsory training modules
(surgery and internal medicine) that is intended to serve as a model (formally
and contentwise) for those who develop similar catalogues for elective training
modules. Here we present our logbook for an elective training module in
orthopaedic surgery and traumatology. MATERIAL AND METHOD: The logbook presented
here is based on the catalogue of learning outcomes in orthopaedic surgery and
traumatology developed by an expert board of the medical teaching study group of
the German Society of Orthopaedic Surgery and Traumatology (DGOU) in 2011. The
objectives defined for the one-year internship are of necessity divided into
orthopaedic surgery and traumatology skills that must be acquired by all medical
students and those that are optional (compulsory and elective modules). Using a
set of predefined criteria, the authors developed the catalogue of learning
outcomes (logbook) presented here. The catalogue outlines the competencies to be
acquired in an elective orthopaedic surgery and traumatology module, leaving it
to each medical faculty to work out the details. Where applicable, comprehensive
skills across a number of (compulsory and elective modules) learning objectives
are arranged in such a way that they can be taught at different levels of
complexity. RESULTS: The logbook covers 15 skill domains from different specific
components of orthopaedic surgery and traumatology. Where these skills overlap
with those also required in compulsory modules (e.g., surgery), the required
level of complexity may be lower for students in the elective module. The text is
supplemented by figures with synopses of the major issues and summaries for easy
reference. CONCLUSION: With the recent changes in German licensing regulations
for physicians, it has become necessary to set up a logbook of uniform learning
outcomes to assist medical students and their teachers alike. The authors have
developed such a logbook of elective training modules in orthopaedic surgery and
traumatology to be taught during the one-year undergraduate internship of German
medical students.
PMID- 24347417
TI - [Radiofrequency kyphoplasty combined with posterior fixation in the treatment of
burst fractures].
AB - PURPOSE: Radiofrequency kyphoplasty is an advancement of the balloon kyphoplasty
and offers comparable results with a shorter operation time and a lower risk of
cement leakage. This prospective study investigates the outcome of radiofrequency
kyphoplasty in combination with posterior fixation by a cement-augmented screw
system. Accordingly, statistical analyses of the treatment data were performed.
MATERIALS AND METHODS: 19 patients (mean age: 74.5 +/- 7.2 years) with
osteoporotic vertebral burst fractures were included in the study. All of them
required a surgical intervention for treating the fracture. Thereby, the
vertebrae were augmented by radiofrequency kyphoplasty and a posterior fixation
by cement-augmentable screws was performed. To evaluate the effectiveness and
safety of the procedure, pain was measured with the visual analog scale (VAS) and
functional impairment was analysed by measuring the Oswestry disability index
(ODI). Furthermore, a radiographic analysis of the anterior and medial height of
the vertebrae and the degree of kyphosis were undertaken. All data were recorded
preoperatively, 3 to 4 days postoperatively, 3 months postoperatively and 6
months postoperatively and any additionally occurring cement leakage was
documented. RESULTS: The treatment showed a significant reduction of pain and
improvement of the functional impairment at the 3 to 4 days postoperative
evaluation (pVAS < 0.001, pODI < 0.001). The further follow-ups demonstrated an
ongoing improvement of the VAS and ODI from each measurement to the next
(pVAS_post-3 M < 0.001, pVAS_3 M-6 M = 0.17, pODI_post-3 M < 0.001, pODI_3 M-6 M
= 0.004). The height of the vertebrae was significantly improved after the
surgery (p_anterior < 0.001, p_medial < 0.001) and reduced slightly from follow
up to follow-up, but still remained higher than the preoperative value. The
degree of kyphosis was also significantly improved after the surgery (p < 0.001),
whereby a significant deterioration was shown at the following examinations
(p_post-3 M = 0.023, p_3 M-6 M = 0.016). But even as the height decreased the
degree of kyphosis was still improved in relation to the preoperative values.
During the surgery cement leakage occurred in 3 cases (15.79 %). CONCLUSION:
Radiofrequency kyphoplasty is a safe and effective procedure for the treatment of
vertebral compression fractures in combination with the use of posterior fixation
by cement-augmentable screws with an acceptable rate of cement leakage.
PMID- 24347418
TI - [Scaphoid fractures and pseudarthrosis of the scaphoid].
AB - Scaphoid fractures are by 80 % the most common fractures of the carpal bones.
Detection and treatment can be delayed due to only slight clinical symptoms,
which are often shown by acute injuries of the scaphoid. Pseudarthrosis of the
scaphoid developing arthrosis of the wrist or even a carpal collapse can be the
consequence. An in-depth clinical examination and adequate radiological
diagnostics are essential for the detection and the treatment of scaphoid
fractures. A primary examination by CT scan is obligatory. The classification of
Krimmer/Herbert in the CT is used to subdivide the scaphoid fractures. Depending
on the appearance of the fracture a conservative or surgical approach is
indicated. All stable fractures of the scaphoid can be treated conservatively. In
all forms of unstable scaphoid fractures surgery is recommended. Different ways
of surgical approaches and osteosyntheses are described. Pseudarthrosis of the
scaphoid should be surgically reconstructed with osteosynthesis in combination
with bone graft to prevent a carpal collapse.
PMID- 24347420
TI - Cortical photothrombotic infarcts impair the recall of previously acquired
memories but spare the formation of new ones.
AB - BACKGROUND AND PURPOSE: Despite a high incidence of poststroke dementia, there is
no specific treatment for this condition. Because the evaluation of poststroke
cognitive deficits in animal models of stroke is exceedingly challenging, the
preclinical evaluation of candidate drugs is limited. We aimed to explore the
impact of small cortical photothrombotic strokes on poststroke cognition, thereby
assessing the suitability of this experimental stroke model for the investigation
of cognitive impairment after stroke. METHODS: Photothrombotic cortical infarcts
were induced in 19 adult male Wistar rats. Nineteen sham-operated animals served
as controls. Using the Morris water maze, we analyzed the impact of
photothrombotic stroke on both the acquisition of new memories and the recall of
previously acquired memories. The cylinder test, the adhesive tape removal test,
and the rotarod test were performed to investigate sensorimotor deficits.
RESULTS: Photothrombotic stroke significantly impaired the recall of previously
acquired memories (P<0.05), whereas the acquisition of new memories remained
largely intact. The analysis of the animals' swimming speed in the water maze and
the rotarod test showed no confounding motor impairments after photothrombotic
stroke. The adhesive tape removal test and the cylinder test revealed mild
sensorimotor deficits in lesioned animals (P<0.05). CONCLUSIONS: Photothrombotic
cortical infarcts impair the recall of memories acquired before stroke, whereas
the formation of new memories remains unimpaired. The observed deficits in the
water maze are not confounded by disturbed motor functions. Overall, experimental
photothrombotic strokes are well suited for the investigation of specific
cognitive impairments after stroke.
PMID- 24347423
TI - Diffusion-weighted image and fluid-attenuated inversion recovery image mismatch:
unclear-onset versus clear-onset stroke.
AB - BACKGROUND AND PURPOSE: Mismatch in lesion visibility between diffusion-weighted
image and fluid-attenuated inversion recovery image (DWI-FLAIR mismatch) has been
proposed as a biomarker for the estimation of ischemic lesion age. The actual
onset in some patients with unclear-onset stroke (UnCOS) may be close to the
first-found abnormal time. We hypothesized that patients with UnCOS within a
particular time window might have a similar DWI-FLAIR mismatch profile with
patients with clear-onset stroke (COS). METHODS: Patients who underwent MRI
within 6 hours from first-found abnormal time were recruited retrospectively.
Clinical characteristics and the proportion of DWI-FLAIR and perfusion-weighted
image-DWI mismatch in each time window were compared between UnCOS and COS.
RESULTS: The final analysis included 259 patients (114 with UnCOS and 145 with
COS). Patients with UnCOS were older and had more severe stroke at baseline. Risk
factors, stroke subtypes, and perfusion-weighted image-DWI mismatch did not
differ between the 2 groups. The proportion of patients with DWI-FLAIR mismatch
in UnCOS did not differ from COS within 2 hours of first-found abnormal time
(50.0% versus 51.5%; P=0.92), but it was significantly lower in UnCOS than in COS
at 2 to 3 hours (16.1% versus 44.4%; P=0.02), 3 to 4 hours (13.8% versus 36.4%;
P=0.04), and 4 to 5 hours (5.6% versus 29.6%; P=0.05). CONCLUSIONS: The
proportion of DWI-FLAIR mismatch in UnCOS within the first 2 hours from first
found abnormal time was similar with COS, but it sharply decreased beyond 2
hours. These data suggest that patients with UnCOS within 2 hours of symptom
detection may be good candidates for multimodal imaging-based thrombolysis.
PMID- 24347422
TI - Carotid stenting: is there an operator effect? A pooled analysis from the carotid
stenting trialists' collaboration.
AB - BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of
stroke or death after carotid artery stenting compared with surgery. We examined
whether operator experience is associated with 30-day risk of stroke or death in
the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid
Stenting Trialists' Collaboration is a pooled individual patient database
including all patients recruited in 3 randomized trials of stenting versus
endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus
Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent
Protected Angioplasty versus Carotid Endarterectomy trial, and International
Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime
experience in stenting procedures excluding the carotid, and annual number of
procedures performed within the trial (in-trial volume), divided into tertiles,
were used to measure operator experience. The outcome event was the occurrence of
any stroke or death within 30 days of the procedure. The analysis was done per
protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120
(7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of
stroke or death did not differ according to operator lifetime carotid artery
stenting experience (P=0.8) or operator lifetime stenting experience excluding
the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was
significantly higher in patients treated by operators with low (mean <=3.2
procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate
annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93
[1.14-3.27]) compared with patients treated by high annual in-trial volume
operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be
performed by operators with annual procedure volume >=6 cases per year.
PMID- 24347424
TI - Reperfusion injury on magnetic resonance imaging after carotid revascularization.
AB - BACKGROUND AND PURPOSE: Reperfusion injury can be revealed as delayed gadolinium
enhancement in the subarachnoid space on a fluid-attenuated inversion recovery
image, which is designated as a hyperintense acute reperfusion marker (HARM). We
sought to investigate the occurrence and predictors of HARM and its association
with new ischemic infarcts after carotid revascularization. METHODS: Forty-five
patients who underwent carotid endarterectomy or stenting were prospectively
enrolled. Diffusion-weighted imaging and fluid-attenuated inversion recovery were
performed before and 24 hours after the procedures. Postprocedural fluid
attenuated inversion recovery was done after intravenous gadolinium injection.
RESULTS: HARM was observed in 8 (17.8%) patients. Of these, 4 patients showed
neurological deterioration associated with HARM. These symptomatic HARMs
disappeared on follow-up magnetic resonance imaging. Patients with symptomatic
HARM were older (P=0.010) and had more frequent leukoaraiosis (P=0.012) and
higher postprocedural systolic blood pressure (P=0.025) than those without. New
brain infarcts on postprocedural diffusion-weighted imaging were identified in 13
(28.9%) patients. HARM was not associated with new infarcts. CONCLUSIONS: HARM
after carotid revascularization is not uncommon. Symptomatic HARM was associated
with old age, underlying leukoaraiosis, and postprocedural high blood pressure.
PMID- 24347425
TI - Diagnosis of endocrine disease: Biochemical diagnosis of phaeochromocytoma and
paraganglioma.
AB - Adrenal phaechromocytomas and extra-adrenal sympathetic paragangliomas (PPGLs)
are rare neuroendocrine tumours, characterised by production of the
catecholamines: noradrenaline, adrenaline and dopamine. Tumoural secretion of
catecholamines determines their clinical presentation which is highly variable
among patients. Up to 10-15% of patients present entirely asymptomatic and in 5%
of all adrenal incidentalomas a PPGL is found. Therefore, prompt diagnosis of
PPGL remains a challenge for every clinician. Early consideration of the presence
of a PPGL is of utmost importance, because missing the diagnosis can be
devastating due to potential lethal cardiovascular complications of disease.
First step in diagnosis is proper biochemical analysis to confirm or refute the
presence of excess production of catecholamines or their metabolites. Biochemical
testing is not only indicated in symptomatic patients but also in asymptomatic
patients with adrenal incidentalomas or identified genetic predispositions.
Measurements of metanephrines in plasma or urine offer the best diagnostic
performance and are the tests of first choice. Paying attention to sampling
conditions, patient preparation and use of interfering medications is important,
as these factors can largely influence test results. When initial test results
are inconclusive, additional tests can be performed, such as the clonidine
suppression test. Test results can also be used for estimation of tumour size or
prediction of tumour location and underlying genotype. Furthermore, tumoural
production of 3-methoxytyramine is associated with presence of an underlying SDHB
mutation and may be a biomarker of malignancy.
PMID- 24347426
TI - Effects of raloxifene and estrogen on bioactive IGF1 in GH-deficient women.
AB - CONTEXT: GH action is attenuated by estrogens and selective estrogen receptor
modulators (SERMs) administered orally. During GH therapy in hypopituitary women,
co-treatment with raloxifene, a SERM, induced a smaller gain in lean body mass
(LBM) compared with estrogen, despite an equal reduction in IGF1. As a higher IGF
binding protein-3 (IGFBP3) level was observed with raloxifene co-treatment, we
hypothesize that an increase in IGFBP3 reduced IGF1 bioactivity causing the
attenuated anabolic effect. OBJECTIVE: To assess the effects of 17beta-estradiol
(E2) and raloxifene on bioactive IGF1. DESIGN: In study 1, 12 GH-deficient (GHD)
women were randomized to raloxifene 120 mg/day or E2 4 mg/day for 1 month. In
study 2, 16 GHD women were randomized to 1 month GH treatment alone (0.5 mg/day)
and in combination with raloxifene (60 mg/day) or E2 (2 mg/day). We measured
bioactive IGF1, immunoreactive IGF1 and IGF2, and IGFBP3 immunoreactivity and
fragmentation. RESULTS: Raloxifene and estrogen suppressed (P<0.05) total IGF1
equally in GHD and GH-replaced hypopituitary women. In GHD patients, neither
raloxifene nor estrogen affected bioactive IGF1. GH significantly increased IGF1
bioactivity, an effect attenuated by co-treatment with raloxifene (Delta -23 +/-
7%, P<0.01) and estrogen (Delta -26 +/- 3%, P=0.06). Total IGF1 correlated
(r(2)=0.54, P<0.001) with bioactive IGF1, which represented 3.1 +/- 0.2% of the
total IGF1, irrespective of the treatments. Total IGF2 was unchanged by
raloxifene and estrogen treatment. IGFBP3 was significantly higher during
raloxifene administration, whereas no differences in IGFBP3 fragmentation were
observed. CONCLUSION: Raloxifene effect on bioactive IGF1 is similar to that of
estrogen despite higher IGFBP3 levels during raloxifene administration. We
conclude that the observed different effects on LBM between raloxifene and
estrogen treatments cannot be explained by differences in IGF1 bioactivity.
PMID- 24347427
TI - Mass-array screening of frequent mutations in cancers reveals RB1 alterations in
aggressive adrenocortical carcinomas.
AB - CONTEXT: Adrenocortical carcinoma (ACC) is a rare disease with a poor overall
outcome. Transcriptome analysis identified two groups of ACCs with different
prognosis. In aggressive ACCs, somatic mutations of the tumor suppressor gene
TP53 and the proto-oncogene beta-catenin are detected in 50% of cases. For the
remaining aggressive ACCs and for the group with a better prognosis, molecular
alterations are unknown. OBJECTIVE: To identify new molecular actors driving
adrenal tumorigenesis. EXPERIMENTAL DESIGN: Analysis by mass array of 374
mutations among 32 common oncogenes or tumor suppressor genes was performed on
the tumoral DNA of 26 ACCs, using Sequenom OncoCarta Panels. RESULTS: Four
mutations were identified, two previously known beta-catenin mutations and one
alteration in two other genes: JAK3 and retinoblastoma gene (RB1). The JAK3
alteration was found in leukocyte DNA and therefore considered as a polymorphism
and not a somatic event. The full RB1 tumor suppressor gene was subsequently
sequenced in a cohort of 49 ACCs (26 ACCs from the 'OncoCarta cohort' and 23
other ACCs): three somatic mutations were identified, all in the poor-outcome ACC
group. By immunohistochemistry, a loss of the retinoblastoma protein (pRb) was
found exclusively in aggressive ACCs in 27% of cases (seven out of 26), three of
them with an inactivating RB1 mutation. Among the seven pRb-negative ACCs, five
had an allele loss at the RB1 locus. CONCLUSIONS: Parallel analysis of somatic
mutations among known cancer genes allowed us to identify RB1 as a new actor in
aggressive ACCs. These results suggest a prognostic significance of pRb
expression loss in ACCs.
PMID- 24347428
TI - Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are
reduced in women with polycystic ovary syndrome.
AB - OBJECTIVE: Pentraxin-3 (PTX3), like C-reactive protein (CRP), is an acute-phase
protein that belongs to the pentraxin superfamily. Moreover, it is expressed in
the cumulus oophorus and appears to be involved in female fertility. The aim of
the present study was to assess whether PTX3 levels are altered in polycystic
ovary syndrome (PCOS) women and whether they show any relationship with the main
features of these subjects. DESIGN: A cross-sectional study was conducted at the
outpatient clinic of an academic centre. METHODS: A total of 66 women affected
with PCOS and 51 healthy controls were studied. Plasma PTX3 and serum CRP were
measured by ELISA. Androgens were measured by liquid chromatography-mass
spectrometry and free testosterone was measured by equilibrium dialysis. In PCOS
women, insulin sensitivity was assessed by the glucose clamp technique. RESULTS:
Adjusting for age and BMI, plasma PTX3 was reduced in PCOS women (P=0.036), in
contrast with serum CRP, which was increased (P=0.004). In multiple regression
analysis, serum androgens and other endocrine and ovarian features of PCOS were
predictors of PTX3 levels, whereas body fat was the main independent predictor of
CRP concentrations. CONCLUSIONS: Plasma PTX3 levels were reduced in PCOS women
and independently associated with hyperandrogenism and other endocrine and
ovarian features of PCOS.
PMID- 24347429
TI - The inverse electron demand Diels-Alder click reaction in radiochemistry.
AB - The inverse electron-demand Diels-Alder (IEDDA) cycloaddition between 1,2,4,5
tetrazines and strained alkene dienophiles is an emergent variety of catalyst
free 'click' chemistry that has the potential to have a transformational impact
on the synthesis and development of radiopharmaceuticals. The ligation is
selective, rapid, high-yielding, clean, and bioorthogonal and, since its advent
in 2008, has been employed in a wide variety of chemical settings. In
radiochemistry, the reaction has proven particularly useful with (18) F and has
already been utilized to create a number of (18) F-labeled agents, including the
PARP1-targeting small molecule (18) F-AZD2281, the alphav beta3 integrin
targeting peptide (18) F-RGD, and the GLP-1-targeting peptide (18) F-exendin.
The inherent flexibility of the ligation has also been applied to the
construction of radiometal-based probes, specifically the development of a
modular strategy for the synthesis of radioimmunoconjugates that effectively
eliminates variability in the construction of these agents. Further, the
exceptional speed and biorthogonality of the reaction have made it especially
promising in the realm of in vivo pretargeted imaging and therapy, and
pretargeted imaging strategies based on the isotopes (111) In, (18) F, and (64)
Cu have already proven capable of producing images with high tumor contrast and
low levels of uptake in background, nontarget organs. Ultimately, the
characteristics of inverse electron-demand Diels-Alder click chemistry make it
almost uniquely well-suited for radiochemistry, and although the field is young,
this ligation has the potential to make a tremendous impact on the synthesis,
development, and study of novel radiopharmaceuticals.
PMID- 24347430
TI - Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma:
results of the accelerated radiotherapy with carbogen breathing and nicotinamide
phase III randomized trial.
AB - BACKGROUND: The prognostic and predictive value of the proliferation marker Ki-67
was investigated in a randomized trial comparing accelerated radiotherapy with
carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in
laryngeal carcinoma. METHODS: Labeling index of Ki-67 (Li Ki-67) in
immunohistochemically stained biopsies and the colocalization with carbonic
anhydrase IX (CAIX) were related to tumor control and patient survival. RESULTS:
On average, node-positive patients had a higher Li Ki-67 (median 14% vs 8%; p <
.01). In patients with a high Li Ki-67, the 5-year regional control and
metastases-free survival were 79% versus 96% (p < .01) and 71% versus 88% (p =
.05) for accelerated radiotherapy and ARCON, respectively. The 5-year local
control and disease-specific survival were not significantly different. Patients
with low Ki-67 expression had an excellent outcome with accelerated radiotherapy
alone. CONCLUSION: Patients with laryngeal carcinomas with high proliferative
activity are at increased risk of regional and distant metastases formation. This
risk can be reduced by treatment with ARCON.
PMID- 24347431
TI - Use of the mouse ear vesicant model to evaluate the effectiveness of ebselen as a
countermeasure to the nitrogen mustard mechlorethamine.
AB - Previous studies in this and other laboratories have demonstrated that ebselen
(EB-1), an organoselenium compound, spares cells from mechlorethamine (HN2)
toxicity in vitro. In the present study, the hypothesis that EB-1 will reduce
dermal toxicity of HN2 in vivo is put forward and found to have merit. Using the
mouse ear vesicant model (MEVM), HN2, applied topically, showed a dose-dependent
effect upon ear swelling and thickness 24 h after treatment; whereas tissue
injury consistent with vesication was observed at the higher test doses of HN2
(>= 0.250 umol per ear). To examine HN2 countermeasure activity using the MEVM,
either hydrocortisone (HC), as a positive control, or EB-1, the test
countermeasure, was administered as three topical treatments 15 min, 4 and 8 h
after HN2 exposure. Using this approach, both HC and EB-1 were found to reduce
tissue swelling associated with HN2 toxicity 24 h after exposure to the vesicant.
Taken together, these data demonstrate for the first time the effectiveness of EB
1 as a vesicant countermeasure in a relevant in vivo model.
PMID- 24347432
TI - Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys
(Macaca fascicularis).
AB - The purpose of this study was to determine the timing of the onset of adult-type
sulcal length asymmetry during postnatal development of the male cynomolgus
monkey cerebrum. The monkey brain has already reached adult size by 3 months of
age, although the body weight only represents 1/8 of the adult body weight by
that time. The fronto-occipital length and the cerebral width also reached adult
levels by that postnatal age with no left/right bias. Consistently, lengths of
the major primary sulci reached adult levels by 3 months of age, and then
decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry
quotient analysis showed that sulcal length asymmetry patterns gradually changed
during postnatal development. The male adult pattern of sulcal length asymmetry
was acquired after 24 months of age. In particular, age-dependent rightward
lateralization of the arcuate sulcal length was revealed during cerebral
maturation by three-way ANOVA. The results suggest that the regional difference
in cerebral maturation from adolescence to young adulthood modifies the sulcal
morphology with characteristic asymmetric patterns in male cynomolgus monkeys.
PMID- 24347433
TI - Simultaneous detection of three antiviral and four antibiotic compounds in source
separated urine with liquid chromatography.
AB - An analytical method for the simultaneous screening of three antiviral agents
(nevirapine, zidovudine, lamivudine), four antibiotics (sulfamethoxazole,
trimethoprim, ciprofloxacin, rifampicin) and one reference compound
(carbamazepine) in human urine was developed. Separation was achieved with a
Kinetex XB-C18 (75 * 4.6 mm, 2.6 MUm) column after the extraction of
pharmaceuticals from urine with SPE. Gradient elution with a mobile phase
consisting of acetonitrile and 10 mM KH2 PO4 (pH 2.5), and diode array detection
with monitoring at 210 and 264 nm was applied. The developed method was validated
in terms of selectivity, linearity, stability and sensitivity. Repeatability (n =
3) and between-day precision (n = 3) revealed RSD <5%. The detection limits were
estimated as 0.02-0.54 g/L (depending on compound). The method was validated for
human urine and successfully applied to the simultaneous quantification of
selected compounds. Strata-X cartridges provided good recoveries ranging from 81
to 109%. The limits of detection for urine varied between 0.04 and 1.61 g/L. The
method is suitable for the fast determination of selected pharmaceuticals from
source-separated urine samples for further environmental risk assessment and
degradation potential evaluation. It provides a way to enhance safe nutrient
recycling from wastewater streams and promotes the safe use of urine as
fertiliser.
PMID- 24347434
TI - Influence of health-insurance access and hospital retention policies on childhood
cancer treatment in Kenya.
AB - BACKGROUND: Kenyan national policies for public hospitals dictate that patients
are retained on hospital wards until their hospital bills are paid, but this
payment process differs for patients with or without access to National Hospital
Insurance Fund (NHIF) at diagnosis. Whether these differences impact treatment
outcomes has not been described. Our study explores whether childhood cancer
treatment outcomes in Kenya are influenced by health-insurance status and
hospital retention policies. PROCEDURE: This study combined retrospective review
of medical records with an illustrative case report. We identified children
diagnosed with malignancies at a large Kenyan academic hospital between 2007 and
2009, their treatment outcomes, and health-insurance status at diagnosis.
RESULTS: Between 2007 and 2009, 222 children were diagnosed with malignancies.
Among 180 patients with documented treatment outcome, 54% abandoned treatment,
22% had treatment-related death, 4% progressive/relapsed disease, and 19% event
free survival. Health-insurance status at diagnosis was recorded in 148 children:
23% had NHIF and 77% had no NHIF. For children whose families had NHIF compared
with those who did not, the relative risk for treatment abandonment relative to
event-free survival was significantly smaller (relative-risk ratio = 0.31, 95% CI
= 0.12-0.81, P = 0.016). The case report illustrates difficulties that Kenyan
families might face when their child is diagnosed with cancer, has no NHIF, and
is retained in hospital. CONCLUSIONS: Children with NHIF at diagnosis had
significantly lower chance of abandoning treatment and higher chance of survival.
Childhood cancer treatment outcomes could be improved by interventions that
prevent treatment abandonment and improve access to NHIF. Hospital retention of
patients over unpaid medical bills must stop.
PMID- 24347435
TI - An easy and effective method to modulate molecular energy level of the polymer
based on benzodithiophene for the application in polymer solar cells.
AB - Attaching meta-alkoxy-phenyl groups as conjugated side chains is an easy and
effective way to modulate the molecular energy level of D-A polymer for
photovoltaic application, and the polymer solar cells based on the polymer
consisting meta-alkoxy-phenyl groups as conjugated side chain, PBT-OP, shows an
enhanced open circuit voltage and thus higher efficiency of 7.50%, under the
illumination of AM 1.5G, 100 mW/cm(2) .
PMID- 24347436
TI - Un Abrazo Para La Familia: an evidenced-based rehabilitation approach in
providing cancer education to low-SES Hispanic co-survivors.
AB - We discuss Un Abrazo Para La Familia as an effective, rehabilitation-informed
evidence-based model of education, information-sharing, and skill teaching for
use with low-income Hispanic co-survivors of cancer. Over 2 years, 120 co
survivors participated in the intervention. The majority of participants (96 %)
were women and all but one reported being Hispanic. Both in years 1 and 2, we
followed the same pre- and post-intervention evaluation design. Based on pre- and
post-intervention assessments of cancer-related knowledge and self-efficacy, the
percentage of questions answered correctly about cancer significantly increased
for co-survivors. Self-efficacy significantly increased as well. Using item
analysis, we explored skill teaching as a mechanism for the effective delivery of
Un Abrazo and recommend the use of promotoras in providing the intervention. Of
the 12 cancer knowledge items resulting in statistically significant increases of
cancer knowledge, 5 were taught via interactive skill teaching. Given the
projected rise in the incidence of cancer in Hispanic populations, coupled with
the fact that people from low-income backgrounds face unique challenges in cancer
prevention and management, implications of the Un Abrazo model for future
research and policy regarding cancer and families are considered.
PMID- 24347437
TI - Olfactory neuroblastoma: a 35-year experience and suggested follow-up protocol.
AB - OBJECTIVES/HYPOTHESIS: To validate a follow-up protocol based on the long-term
outcomes and recurrence rates in patients who have undergone surgical treatment
for olfactory neuroblastoma. METHODS: A prospective review of all patients
treated for olfactory neuroblastoma at our institution over a 35-year period.
RESULTS: Ninety-five patients were treated from 1978 to 2013, with craniofacial
(65 patients) or endoscopic resection (30 patients). Duration of follow-up ranged
from 1 to 309 months (mean, 88.66 months). Fifty-six patients were alive and
well, and 13 were alive with recurrent disease. Twenty-one patients had died of
disease, and three had died of intercurrent disease. Overall survival was 83.4%
at 5 years and 76.1% at 10 years. Disease-free survival at 5 years was 80% and at
10 years was 62.8%. A Cox regression analysis showed orbital extension and
intracranial involvement to be significant independent factors affecting outcome.
Local and regional recurrence occurred after an average of 49 months but with a
range of 3 to 233 months. CONCLUSIONS: In our series, olfactory neuroblastoma
most commonly recurred within the first 4 years but can recur very late, after
19.4 years in one case. There is currently no universally accepted follow-up
regime, but even late recurrence is eminently treatable. We therefore propose a
protocol for lifelong follow-up with both clinical examination and serial
imaging, including the neck and entire intracranial compartment. LEVEL OF
EVIDENCE: 4.
PMID- 24347438
TI - Pamidronate attenuates muscle loss after pediatric burn injury.
AB - Children who are burned >40% total body surface area lose significant quantities
of both bone and muscle mass because of acute bone resorption, inflammation, and
endogenous glucocorticoid production, which result in negative nitrogen balance.
Because administration of the bisphosphonate pamidronate within 10 days of the
burn injury completely prevents the bone loss, we asked whether muscle protein
balance was altered by the preservation of bone. We reviewed the results from 17
burned pediatric subjects previously enrolled in a double-blind randomized
controlled study of pamidronate in the prevention of post-burn bone loss and who
were concurrently evaluated for muscle protein synthesis and breakdown by stable
isotope infusion studies during the acute hospitalization. We found a
significantly lower fractional protein synthesis rate (FSR) in the pamidronate
group and a correspondingly lower rate of appearance of the amino acid tracer in
venous blood, suggesting lower muscle protein turnover. Moreover, net protein
balance (synthesis minus breakdown) was positive in the subjects receiving
pamidronate and negative in those receiving placebo. Muscle fiber diameter was
significantly greater in the pamidronate subjects and leg strength at 9 months
post-burn was not different between subjects who received pamidronate and normal
physically fit age-matched children studied in our lab. Leg strength in burned
subjects who served as controls tended to be weaker, although not significantly
so. If substantiated by a larger study, these results suggest that bone may have
a paracrine mechanism to preserve muscle and this finding may have implications
for the treatment of sarcopenia in the elderly.
PMID- 24347439
TI - Single molecule mechanical manipulation for studying biological properties of
proteins, DNA, and sugars.
AB - For over 20 years there has been immense biological insight gained using single
molecule mechanical measurements to understand properties of biomolecules. This
review outlines the field of single molecule mechanics studies and focuses on the
manipulation of proteins, DNA, and sugars by single molecule force spectroscopy
(SMFS) by atomic force microscopy (AFM). The methods and examples of SMFS by AFM
are illustrated using recent advances in protein science including titin
elasticity, mechanical unfolding and refolding of alpha-helical repeat proteins,
mechanoenzymatics of thioredoxin and titin kinase, and intermolecular
interactions of P-selectin complexes. The possibilities of SMFS to investigate
the mechanics of other biopolymers like double- and single-stranded DNA and
forced-induced conformational changes in sugars are also discussed. Finally, SMFS
and its application to biological processes, like DNA replication, packing and
transcription, and DNA methylation are illustrated. These measurements provide a
unique and integral part of the development of our knowledge of biochemistry and
molecular mechanics.
PMID- 24347440
TI - Effects of 2 different swallowing exercise regimens during organ-preservation
therapies for head and neck cancers on swallowing function.
AB - BACKGROUND: This study investigated the effects of 2 different swallowing
exercise regimens performed during radiation therapy with/without chemotherapy on
swallowing function. METHODS: Fifty patients were recruited prospectively to 2
groups (the exercise group, n = 26 and the repetitive swallow group, n = 24).
Functional Oral Intake Scale (FOIS) scores and percutaneous endoscopic
gastrostomy (PEG) placements were compared at posttreatment and at 3 months.
RESULTS: The exercise group eliminated significantly more PEG tubes at 3 months
posttreatment compared to the swallow group (16% vs 50%). Among patients who
received both radiation and chemotherapy, the exercise group had significantly
less PEG tubes immediately posttreatment as well as 3 months posttreatment (35%
and 10%), compared to the swallow group (69% and 50%). CONCLUSION: Findings
indicate significant benefits of the exercise group's exercise regimen in
reducing PEG dependence and oral intake difficulties.
PMID- 24347441
TI - Divergent coverage, frequency and costs of organised and opportunistic Pap
testing in Finland.
AB - We evaluated the overall coverage, frequency and costs of Pap testing by
screening modality and health care provider in Finland. Information about Pap
testing in the Finnish female population of 2.7 million was obtained from
nationwide population-based registry data. Among women aged 25-69 years, 87% had
had a Pap test taken within or outside the organised programme at least once
during the last 5 years and half of those screened in the organised programme had
also had at least one Pap test taken outside the programme. Of the annual average
of 530,000 Pap tests taken, 84% were taken for screening purposes and 16% as
follow-up. Forty percent of the 446,000 annual screening tests were taken in the
organised programme, 55% as opportunistic tests in public primary or student
health care or by private providers and 5% in public secondary health care. One
fifth of all opportunistic screening Pap tests were taken from women aged <25.
The voluminous opportunistic Pap testing in public primary health care was
concentrated in young women aged 25-29 whereas the bulk of opportunistic testing
in private health occurred in age groups eligible for organised screening. The
total cost of all screening Pap tests was ?22.4 million, of which 71% incurred in
opportunistic screening. Of the 84,000 annual follow-up Pap tests and their ?8.3
million total costs, ~60% incurred in organised screening or in secondary health
care.
PMID- 24347442
TI - Combination of S-adenosylhomocysteine and scriptaid, a non-toxic epigenetic
modifying reagent, modulates the reprogramming of bovine somatic-cell nuclear
transfer embryos.
AB - The goal of this study was to improve the development of bovine somatic-cell
nuclear transfer (SCNT) embryos by optimizing the combination of DNA
methyltransferases inhibitor S-adenosylhomocysteine (SAH) and histone deacetylase
inhibitor Scriptaid (SPD). A. 4 * 4-factor design of different drug combinations
(0, 0.75, 1.0, and 1.5 mM SAH and 0, 5, 250, and 500 nM SPD) was used to identify
an optimal combination of 0.75 mM SAH and 250 nM SPD that improved the
developmental competence of bovine SCNT embryos. Further experiments using this
combination revealed that methylation levels of CpG islands near exon 1 of the
pluripotent gene SOX2; the epigenetic-related gene HDAC3 and DNMT3a; imprinted
genes XIST and PEG3; as well as apoptosis-related genes BCL2 and BAX were
returned to levels similar to those of in vitro fertilized (IVF) embryo after
treatment, which also normalized transcript levels for these genes. This
combination also returned global DNA methylation to a normal level, correcting
H4K12ac levels while enhancing H3K9ac levels. Thus, the combined application of
0.75 mM SAH and 250 nM SPD can significantly improve the reprogramming of bovine
SCNT embryos by stabilizing how embryos utilize their genomes.
PMID- 24347443
TI - Polycyclic aromatic hydrocarbons as test probes to investigate the retention
behavior of 1,3-alternate calix[4]arene silica-bonded stationary phases.
AB - A series of polycyclic aromatic hydrocarbons (PAHs) of different size and shape
has been used to characterize the chromatographic behavior of five calix[4]arene
stationary phases in 1,3-alternate conformation synthesized in our laboratory.
The selection of linear, four-ring nonlinear, and five-ring PAHs gave data on
selectivity changes across range of the calix[4]arene columns. Retention of the
12 aromatic solutes has been evaluated at various methanol contents in the mobile
phase (70-100% v/v) and column temperatures (20-45 degrees C). The thermodynamic
parameters underlying the retention mechanisms revealed that each of the five
calix[4]arene columns exhibited variation in selectivity and retention of PAHs
caused by enthalpy and entropy effects. The calixarene stationary phases
substituted with electron-withdrawing groups exhibit enhanced selectivity toward
PAHs in comparison to the rest of the investigated columns. The observed
divergences are due to differences in solute-stationary phase interactions and
originate in pi-pi and pi-electron transfer specific to the analytes and the type
of calix[4]arene functionalization at the upper rim, as well as steric and
sorption phenomena.
PMID- 24347444
TI - Impact of hyperthermia on pharmacokinetics of intraperitoneal mitomycin C in rats
investigated by microdialysis.
AB - BACKGROUND AND OBJECTIVES: Patients with peritoneal surface malignancies are
treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy,
commonly using mitomycin C (MMC). The purpose of this study was to investigate
impact of hyperthermia on pharmacokinetics of intraperitoneal MMC. METHODS: In 14
athymic nude male rats, microdialysis (MD) probes were implanted in jugular vein
(V), hind leg muscle (M) and extraperitoneal space (XP). Probes were calibrated
by retrodialysis. Intraperitonal chemotherapy perfusion (IPEC) was administered
over 90 min with MMC 5 mg/kg and saline 0.9% 500 ml/kg at 35 and 41 degrees C,
defining the normothermic (NG) and hyperthermic groups (HG), respectively. MD and
peritoneal perfusion fluid (PPF) samples were collected at 10 min intervals to
determine MMC concentration. RESULTS: Time-concentration curves were virtually
parallel between temperature groups, with equal peak concentrations (uM) of 0.3
(V), 0.7 (XP) and 0.3 (M). The following area under time-concentration curve
(AUC) ratios were calculated: AUC PPF/AUC V were 69 in NG and 79 in HG (P =
0.54); AUC XP/AUC V were 2.7 in NG and 2.6 in HG (P = 0.90). CONCLUSIONS: IPEC
provides high intraperitoneal MMC concentration and increased bioavailability in
extraperitoneal tissue, combined with low systemic absorption. Hyperthermia at 41
degrees C did not modify MMC pharmacokinetics.
PMID- 24347446
TI - Waffle Y technique: pCONus for tandem bifurcation aneurysms of the middle
cerebral artery.
AB - Broad based bifurcation aneurysms are challenging. Various endovascular
techniques aim at stabilizing the coil package in the aneurysm. Among these, the
waffle cone technique provides a viable alternative to Y stenting in selected
cases, incorporating a less complex delivery, and the reduced inherent risk of a
single stenting procedure compared with the use of two stents in Y configuration.
Unlike conventional stents, the distal end of the new pCONus device opens like a
blossoming flower inside of the aneurysm to facilitate the waffle cone technique.
In a case with tandem unruptured broad based middle cerebral artery bifurcation
aneurysms, the complex anatomical challenge was resolved by a unique combination
of both techniques: two pCONus deployed in Y configuration, offering stable neck
coverage for coiling both aneurysms. The angiographic results with complete
occlusion of both aneurysms and the uneventful clinical course at 90 days with
continued daily administration of dual antiplatelet therapy are encouraging.
PMID- 24347445
TI - Tbx4 interacts with the short stature homeobox gene Shox2 in limb development.
AB - BACKGROUND: The short stature homeodomain transcription factors SHOX and SHOX2
play key roles in limb formation. To gain more insight into genes regulated by
Shox2 during limb development, we analyzed expression profiles of WT and Shox2-/-
mouse embryonic limbs and identified the T-Box transcription factor Tbx4 as a
potential downstream target. Tbx4 is known to exert essential functions in
skeletal and muscular hindlimb development. In humans, haploinsufficiency of TBX4
causes small patella syndrome, a skeletal dysplasia characterized by anomalies of
the knee, pelvis, and foot. RESULTS: Here, we demonstrate an inhibitory
regulatory effect of Shox2 on Tbx4 specifically in the forelimbs. We also show
that Tbx4 activates Shox2 expression in fore- and hindlimbs, suggesting Shox2 as
a feedback modulator of Tbx4. Using EMSA studies, we find that Tbx4/TBX4 is able
to bind to distinct T-box binding sites within the mouse and human Shox2/SHOX2
promoter. CONCLUSIONS: Our data identifies Tbx4 as a novel transcriptional
activator of Shox2 during murine fore- and hindlimb development. Tbx4 is also
regulated by Shox2 specifically in the forelimb bud possibly via a feedback
mechanism. These data extend our understanding of the role and regulation of Tbx4
and Shox2 in limb development and limb associated diseases.
PMID- 24347447
TI - Renal cell carcinoma metastasis to the cerebellopontine cistern: intraoperative
Onyx embolization via direct needle puncture.
AB - We report a rare case of a renal cell carcinoma (RCC) metastasis occupying the
cerebellopontine and cerebellomedullary cisterns, and describe an alternative
strategy for embolizing hypervascular intracranial tumors. A middle aged patient
with a distant history of RCC presented with headaches, nausea, and vomiting, and
was found to have an enhancing mass in the left cerebellopontine and
cerebellopontine cisterns. The initial surgical resection was aborted due to
excessive bleeding. After an unsuccessful attempt at intra-arterial embolization,
the patient returned to the operating room and the tumor was devascularized by
direct needle puncture Onyx embolization under biplane fluoroscopy. The
devascularized tumor was then successfully dissected from the brainstem and
adherent lower cranial nerves. In properly selected cases, open surgical direct
needle puncture embolization of intracranial vascular tumors under biplane
fluoroscopy is a viable alternative devascularization method.
PMID- 24347448
TI - Optic pathway infarct after Onyx HD 500 aneurysm embolization: visual pathway
ischemia from superior hypophyseal artery occlusion.
AB - We report a case of visual deterioration after Onyx HD 500 embolization of a left
7 mm superior hypophyseal artery (SHA) aneurysm. After the procedure, the patient
experienced a right incongruous homonymous hemianopia, and MRI showed an infarct
of the ipsilateral optic chiasm/tract but no evidence of aneurysm mass effect or
embolic cortical infarcts. The optic pathway ischemia is believed to be secondary
to Onyx penetration and occlusion of an SHA branch near the aneurysm neck.
Caution is advised when using liquid embolic agents to treat SHA aneurysms as SHA
occlusion may lead to visual deficits.
PMID- 24347449
TI - Contact dermatitis due to methyl methacrylate: uncommon and unwanted entity for
dentists.
PMID- 24347450
TI - Doxycycline and suicidality.
AB - A case series outlining three young individuals with no history of mental
disorder who were treated for skin conditions with doxycycline, but developed
suicidal ideation with an outcome of suicide in two of the cases. One of these
individuals had CYP2C19*2 heterozygote genotype associated with a diminished
cytochrome p450 enzyme activity and two of his siblings had developed severe
anxiety previously while on doxycycline. Another had previously developed mood
difficulties on a lower dose of doxycycline which resolved after discontinuation.
In the third individual, a discontinuation of doxycycline has led to the
resolution of symptoms without the need for psychotropic medications.
PMID- 24347451
TI - White-blue pyelocalyceal cyst with hydrotic glomerulonephritis.
AB - A 5-month-old male infant presented with a 15 day history of distension of
abdomen. On clinical examination, a soft lump was palpable in the left lumbar
region. Radiological findings suggested an enlarged non-functional left kidney
with ureteropelvic adhesive obstruction. The left renal mass was excised and
submitted for histopathological examination. The excised renal mass was cystic
with its wall partly white and partly blue. Gross and histopathological findings
were diagnostic of a white-blue pyelocalyceal cyst with hydrotic
glomerulonephritis. This entity needs to be differentiated from a large number of
other cystic diseases of the kidney. Intrauterine screening and diagnosis may be
significant for a possible early intrauterine uro-laparoscopic recanalisation of
the pyeloureteral obstruction to save the affected kidney.
PMID- 24347452
TI - Isolated duodenal varices as the initial presentation of hepatocellular
carcinoma.
AB - Duodenal varices are an uncommon, life-threatening cause of acute
gastrointestinal (GI) bleeding commonly caused by portal hypertension. Though
generally regarded as a complication of advanced cirrhosis and portal
hypertension, often overlooked is that in about 2.7% of cases, it can be the
first presenting symptom of advanced hepatocellular carcinoma (HCC). We report a
case of an isolated, duodenal variceal bleeding as the first clinical
manifestation of HCC, complicated by portal venous thrombosis. Diagnosis of HCC
was established by a markedly elevated alpha-fetoprotein, hepatitis B surface and
core antibody positivity and consistent radiological findings. Although not the
first choice, variceal bleeding was successfully arrested with endoclips. The
patient thereafter declined further evaluation and unsurprisingly died within a
few weeks from a massive GI bleed. An initial bleed from a duodenal varix often
confers a poor prognosis. Patients with HCC who present with variceal bleeding
reportedly have a median survival of 71 days.
PMID- 24347453
TI - Calcifications afloat: bad omens in maxillary sinus augmentation.
PMID- 24347454
TI - Iris retractors: the saviours in cataract surgery for cataract in lens coloboma.
AB - A 67-year-old woman presented with features of bilateral cataract and lens
coloboma. The lens coloboma was from 1 to 8 o'clock and from 5 to 9 o'clock
positions in right and left eye, respectively. With some modifications,
phacoemulsification was performed in both eyes at an interval of 1 month. A
smaller (4.5 mm) anterior capsulorrhexis was made due to poor peripheral
lenticular support. Three iris retractors were used to stabilise anterior
capsulorrhexis margin to the limbus. Phacoemulsification was performed by direct
chop technique under low phacodynamics. A capsular tension ring was placed in a
bag followed by tangential cortical clean up and implantation of a foldable
intraocular lens (IOL). One month following surgery, both eyes had a visual
acuity of 20/20 with a stable IOL. This case report highlights the rarest
malformation of the lens with cataract and its successful management by
phacoemulsification using iris retractors as capsule supporting device.
PMID- 24347455
TI - Spontaneous bilateral compartment syndrome in a HIV-positive patient.
AB - Spontaneous bilateral compartment syndrome is a very rare condition but one which
requires swift diagnosis and urgent surgical decompression by fasciotomies in
order to achieve the best outcome. We present the case of a 31-year-old HIV
positive man. The case highlights the perils of being sidetracked by an atypical
clinical history instead of acting on the classical clinical examination
findings. We will discuss the presentation and management of this patient, review
the literature and highlight the key learning points. The most important learning
point being that no matter how atypical the history, if a patient presents with
limb pain out of proportion to the injury (with or without pain on passive
stretch), sensory changes and a loss of motor power, then a diagnosis of acute
compartment syndrome must be considered.
PMID- 24347456
TI - Prospects for enhancement of targeted radionuclide therapy of cancer using
ultrasound.
AB - Ultrasound-mediated drug delivery is a promising means of enhancing delivery,
distribution and effectiveness of drugs within tumours. In this review, prospects
for exploiting ultrasound to improve the tumour delivery and distribution of
radiolabelled antibodies for radioimmunotherapy and to overcome barriers imposed
by tumour microenvironment are discussed.
PMID- 24347457
TI - Development of hollow fiber-supported liquid-phase microextraction and HPLC-DAD
method for the determination of pyrethroid metabolites in human and rat urine.
AB - A simple hollow fiber liquid-phase microextraction method for the determination
of synthetic pyrethroid metabolites, 3-phenoxybenzoic acid and 4-hydroxy-3
phenoxybenzoic acid, in human and rat urine was developed and validated. A
polypropylene hollow fiber tightly fitted onto a Nylon rod and impregnated with
organic solvent served as a disposable extraction device. Desorption of analytes
was carried out in NaOH solution, analyzed further by gradient HPLC and diode
array detection method. Important factors were identified using Taguchi OA16
(4(5) ) orthogonal array design and further optimized using univariate approach.
The optimum method performance was observed when 1 mL of urine hydrolyzed with
0.2 mL of concentrated HCl was further supplemented with 100 mg of NaCl and
extracted for 120 min into dihexyl ether immobilized in the pores of the hollow
fiber. Metabolites were desorbed into 0.1 mL of 0.1 M NaOH for another 120 min.
Limits of detection and quantitation of 15 and 50 ng/mL were obtained for both
analytes. Relative standard deviations of 1.6-12.6% over the linear range (50
10,000 ng/mL, r > 0.9906) were observed. Intra- and inter-day accuracies of the
method ranged from 98.3 to 109.5% and from 93.3 to 110.9%, respectively. The
optimized method was applied to the analysis of real urine samples collected from
rats exposed orally to cypermethrin.
PMID- 24347458
TI - [Preparation and in-vitro analysis of a polyethylenimine coating on hernia
meshes].
AB - BACKGROUND: Certain coatings such as titanium may improve the biocompatibility of
hernia meshes. The coating with biopolymers such as polyethylenimine (PEI) can
also improve the material characteristics of implants. This approach has,
however, not yet been explored. Thus, it was the aim of the present work to
clarify if and how hernia meshes with their three-dimensional structure can be
successfully coated with PEI and with which technique this coating can be best
analysed. METHODS: Commercially available meshes made from polypropylene,
polyester and ePTFE have been coated with PEI. The coating was analysed via cell
proliferation test (mouse fibroblasts), electron microscopy, X-ray photoelectron
spectroscopy (XPS) and fluorescence microscopy. Cell viability and cytotoxicity
were tested by the MTT test. RESULTS: With the PEI surface modification, mouse
fibroblasts grow faster and in greater numbers on the mesh surface. XPS as well
as fluorescence microscopy show weaknesses in their applicability and
meaningfulness because of the three-dimensional mesh structure while XPS showed
overall better results. Optical proof in the electron microscope after cell
fixation was not unambiguously accomplished with the techniques used here. In the
MTT test, no cellular damage from the PEI coating was detected after 24 hours.
CONCLUSION: The present results show for the first time that PEI coating of
hernia meshes is possible and effective. The PEI coating can be achieved in a
fast and cost-efficient way. Further investigations are necessary with respect to
coating quality and cytotoxicity before such a coating may be used in the
clinical routine. In conclusion, PEI is a promising polymer that warrants further
research as a coating for medical implants.
PMID- 24347459
TI - Voice outcomes following laser cordectomy for early glottic cancer: a physical
model investigation.
AB - OBJECTIVES/HYPOTHESIS: The voice effects following laser cordectomy for early
glottic cancer are poorly described. We investigated the voice outcomes of
subligamentous cordectomy of progressive anterior-posterior extent of excision.
STUDY DESIGN: Physical phonatory modeling. METHODS: The influence of vocal fold
surgical defects and corresponding scar was experimentally investigated using a
self-oscillating physical model of the vocal folds and compared with the baseline
model without defects or scar. RESULTS: Results showed that increasing anterior
posterior extent of resection increased phonation threshold pressure and flow
rate and reduced excitation of high-order harmonics, resulting in a more breathy
and rough voice production. However, it was found that voice production was
improved with the placement of scar, which increased both excitation of high
order harmonics and the harmonic-to-noise ratio. CONCLUSIONS: Although large
anterior-posterior surgical resections resulted in progressive impact on vocal
measures, a limited excision of the vocal fold cover surprisingly demonstrated
minimal voice changes. Further investigations are required to define the
acceptable extent of surgical resection that may result in optimal voice
outcomes.
PMID- 24347460
TI - Benefits and harms of roflumilast in moderate to severe COPD.
AB - BACKGROUND: Roflumilast, a phosphodiesterase 4 inhibitor, has been approved for
the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It
is unclear which patients will have a favourable benefit-harm balance with
roflumilast. Our aim was to quantitatively assess the benefits and harms of
roflumilast (500 ug/day) compared with placebo. METHODS: We used summary data
released by the US Food and Drug Administration to estimate the treatment effects
of roflumilast. Data from trials and observational studies were used to estimate
the baseline risks for COPD exacerbations and gastrointestinal, neurological and
psychiatric harms associated with roflumilast. Using simulation, we calculated
the probability that roflumilast provides net benefit. We examined the impacts of
different baseline risks for exacerbations and the severity of exacerbations, and
varied weights (ie, relative importance) for outcomes and treated death as a
competing risk in the analyses. RESULTS: The probability that roflumilast
provides net benefit approximates 0% across different age categories of men and
women with varying baseline risks for exacerbations. Using different weights for
outcomes did not change the probability that roflumilast provides a net benefit.
Only in the sensitivity analysis restricted to the prevention of severe
exacerbations was there a probability of >50% that roflumilast provides a net
benefit if the baseline risk of having at least one severe exacerbation per year
exceeds 22%. CONCLUSIONS: Our results suggest that roflumilast only provides a
net benefit to patients at a high risk of severe exacerbations. Guideline
developers should consider different recommendations for patients with COPD at
different baseline risks for exacerbations.
PMID- 24347461
TI - Defective IL-10 expression and in vitro steroid-induced IL-17A in paediatric
severe therapy-resistant asthma.
AB - BACKGROUND: Understanding of immune mechanisms underpinning asthma has emerged
from studies in adults. It is increasingly recognised, both immunologically and
in the development of novel therapies, that adult responses cannot be used
accurately to predict those of children. METHODS: Using a well-defined paediatric
cohort of severe therapy-resistant asthma (STRA) patients, we investigated
cytokine profiles in the airway by analysis of bronchoalveolar lavage fluid. The
in vitro capacity of peripheral blood mononuclear cells (PBMCs) for cytokine
production was also assessed following polyclonal T cell activation in culture,
in the absence or presence of dexamethasone and 1alpha,25-dihydroxyvitamin D3.
RESULTS: Children with both moderate and STRA had significantly diminished levels
of anti-inflammatory interleukin (IL)-10 in airway lavage samples when compared
with non-asthmatic controls (p<0.001). Their PBMCs also demonstrated
significantly impaired capacity to secrete IL-10 in culture (p<0.001).
Dexamethasone regulated the balance between PBMC IL-10 and IL-13 production,
increasing IL-10 secretion (p<0.001) and decreasing IL-13 (p<0.001) but
unexpectedly enhanced IL-17A production in all groups-most strikingly in the STRA
cohort (p<0.001). The inclusion of the active form of vitamin D, 1alpha,25
dihydroxyvitamin D3, in culture enhanced dexamethasone-induced IL-10 (p<0.05)
without marked effects on IL-13 or IL-17A production. Furthermore, systemic
vitamin D status directly correlated with airway IL-10 (r=0.6, p<0.01).
CONCLUSIONS: These findings demonstrate reduced peripheral and local IL-10
synthesis in paediatric asthma, and support therapeutic augmentation of low
circulating vitamin D in severe, difficult-to-treat asthma, in order to correct
impaired IL-10 levels. Conversely, steroids enhanced IL-17A levels, and therefore
any steroid-sparing properties of vitamin D may have additional benefit in STRA.
PMID- 24347462
TI - Time to disease progression in children with relapsed or refractory neuroblastoma
treated with ABT-751: a report from the Children's Oncology Group (ANBL0621).
AB - BACKGROUND: ABT-751, an orally bioavailable sulfonamide binds the colchicine site
of beta-tubulin and inhibits microtubule polymerization. Prior phase I studies
established the recommended dose in children with solid tumors as 200 mg/m(2) PO
daily * 7 days every 21 days and subjects with neuroblastoma experienced
prolonged stable disease. We conducted a phase 2 study (NCT00436852) in children
and adolescents with progressive neuroblastoma to determine if ABT-751 prolonged
the time to progression (TTP) compared to a hypothesized standard based on a
historical control population. PROCEDURE: Children and adolescents (n = 91) with
a median (range) age 7.7 (2.3-21.5) years and progressive neuroblastoma were
enrolled and stratified by disease status into disease measureable by CT/MRI (n =
47) or disease assessable by (123) I-metaiodobenzylguanine scintigraphy (MIBG, n
= 44). Response was evaluated using RECIST for measureable disease and the Curie
score for MIBG-avid disease. RESULTS: ABT-751 was well tolerated. The objective
response rate was 7%. The median TTP was 42 days (95% CI: 36, 56) in the
measureable disease stratum and 45 days (95% CI: 42, 85) in the MIBG-avid disease
stratum. TTP was similar to the historical control group (n = 136, median TTP 42
days). For the combined strata (n = 91), 1-year progression free survival (PFS)
was 13 +/- 4% and overall survival (OS) was 48 +/- 5%. CONCLUSIONS: The low
objective response rate and failure to prolong TTP indicate that ABT-751 is not
sufficiently active to warrant further development for neuroblastoma. However,
this trial demonstrates the utility of TTP as the primary endpoint in phase 2
trials in children and adolescents with neuroblastoma.
PMID- 24347463
TI - Understanding and manipulating sucrose phloem loading, unloading, metabolism, and
signalling to enhance crop yield and food security.
AB - Sucrose is produced in, and translocated from, photosynthetically active leaves
(sources) to support non-photosynthetic tissues (sinks), such as developing
seeds, fruits, and tubers. Different plants can utilize distinct mechanisms to
transport sucrose into the phloem sieve tubes in source leaves. While phloem
loading mechanisms have been extensively studied in dicot plants, there is less
information about phloem loading in monocots. Maize and rice are major dietary
staples, which have previously been proposed to use different cellular routes to
transport sucrose from photosynthetic cells into the translocation stream. The
anatomical, physiological, and genetic evidence supporting these conflicting
hypotheses is examined. Upon entering sink cells, sucrose often is degraded into
hexoses for a wide range of metabolic and storage processes, including
biosynthesis of starch, protein, and cellulose, which are all major constituents
for food, fibre, and fuel. Sucrose, glucose, fructose, and their derivate,
trehalose-6-phosphate, also serve as signalling molecules to regulate gene
expression either directly or through cross-talk with other signalling pathways.
As such, sugar transport and metabolism play pivotal roles in plant development
and realization of crop yield that needs to be increased substantially to meet
the projected population demand in the foreseeable future. This review will
discuss the current understanding of the control of carbon partitioning from the
cellular to whole-plant levels, focusing on (i) the pathways employed for phloem
loading in source leaves, particularly in grasses, and the routes used in sink
organs for phloem unloading; (ii) the transporter proteins responsible for sugar
efflux and influx across plasma membranes; and (iii) the key enzymes regulating
sucrose metabolism, signalling, and utilization. Examples of how sugar transport
and metabolism can be manipulated to improve crop productivity and stress
tolerance are discussed.
PMID- 24347464
TI - Transcription factor-mediated cell-to-cell signalling in plants.
AB - Plant cells utilize mobile transcription factors to transmit intercellular
signals when they perceive environmental stimuli or initiate developmental
programmes. Studies on these novel cell-to-cell signals have accumulated multiple
pieces of evidence showing that non-cell-autonomous transcription factors play
pivotal roles in most processes related to the formation and development of plant
organs. Recent studies have explored the evolution of mobile transcription
factors and proposed mechanisms for their trafficking through plasmodesmata,
where a selective system exists to facilitate this process. Mobile transcription
factors contribute to the diversity of the intercellular signalling network,
which is also established by peptides, hormones, and RNAs. Crosstalk between
mobile transcription factors and other intercellular molecules leads to the
development of complex biological signalling networks in plants. The regulation
of plasmodesmata appears to have been another major step in controlling the
intercellular trafficking of transcription factors based on studies of many
plasmodesmal components. Furthermore, diverse omics approaches are being
successfully applied to explore a large number of candidate transcription factors
as mobile signals in plants. Here, we review these fascinating discoveries to
integrate current knowledge of non-cell-autonomous transcription factors.
PMID- 24347465
TI - Visualization of the actin cytoskeleton: different F-actin-binding probes tell
different stories.
AB - The actin cytoskeleton is necessary for cell viability and plays crucial roles in
cell motility, endocytosis, growth, and cytokinesis. Hence visualization of
dynamic changes in F-actin distribution in vivo is of central importance in cell
biology. This has been accomplished by the development of fluorescent protein
fusions to actin itself or to various actin-binding proteins, actin cross-linking
proteins, and their respective actin-binding domains (ABDs). Although these
protein fusions have been shown to bind to F-actin in vivo, we show that the
fluorescent protein used for visualization changes the subset of F-actin labeled
by an F-actin ABD probe. Further, different amino acid linkers between the
fluorescent protein and ABD induced a similar change in localization. Although
different linkers and fluorescent proteins can alter the subset of actin bound by
a particular ABD, in most cases, the fusion protein did not label all of a cell's
F-actin all of the time. Even LimEDeltacoil and GFP-actin, which have been used
extensively for cytoskeletal visualization, were highly variable in the subsets
of actin that they labeled. Lifeact, conversely, clearly labeled cortical F-actin
as well as F-actin in the anterior pseudopods of motile cells and in
macropinocytotic cups. We conclude that Lifeact most accurately labels F-actin
and is the best currently available probe for visualization of dynamic changes in
F-actin networks.
PMID- 24347466
TI - Microcavity-embedded, colour-tuneable, transparent organic solar cells.
AB - In this work microcavity-capped colour-tuneable SMOSCs are evaluated. By adopting
a microcavity-structured cathode with optical spacer layers of different
thicknesses fabricated in a Ag/NPB/Ag structure, the transmission spectra of
complete devices can be tuned over the entire visible-light region (400-750 nm).
The fabricated semitransparent colour-tuneable solar cells show an average
efficiency of 4.78% under 1-sun illumination.
PMID- 24347467
TI - Knowledge, attitudes and behaviour regarding nutrition and dietary intake of
seventh-grade students in rural areas of Mi Yun County, Beijing, China.
AB - OBJECTIVES: To investigate the knowledge, attitudes and behaviour of seventh
grade students regarding nutrition and dietary intake, to collect data that would
facilitate the design and implementation of interventions aimed at promoting good
nutrition in adolescents via the school and to contribute to the improvement of
adolescents' health in rural regions. METHODS: This was a descriptive, cross
sectional study in which a 27-item, self-administered, structured questionnaire,
designed in Chinese, was administered to seventh-grade students attending one of
three rural middle schools, chosen randomly from 15 middle schools, in Mi Yun
County, Beijing. RESULTS: In terms of nutrition knowledge, 84.5 % of respondents
had scores of between 3 and 7. Based on our analysis of the completed
questionnaires, during the 7 days preceding completion of the questionnaire 43.6
% of respondents had eaten fresh fruit at least once per day, 71.3 % had eaten
vegetables at least once per day, 22.3 % had consumed at least one glass of milk
(or soy milk or yogurt) each day and 68.6 % had eaten breakfast every day. In
total, 95.2 % of respondents thought nutrition was very important or important to
their health, and 94.2 % thought it was very important or important to develop
healthy dietary habits. Of the respondents, 52.7 % thought good food quality was
the most important aspect of nutrition and dietary intake and 62.2 % thought food
safety was the most important aspect. CONCLUSIONS: Based on the results of our
survey we suggest their should be continuous efforts to teach adolescents in
rural areas of China about various aspects of good nutrition, to encourage
diversity in their choice of breakfasts, to guarantee food safety and to improve
food quality.
PMID- 24347468
TI - Association between mobile phone use and depressed mood in Japanese adolescents:
a cross-sectional study.
AB - OBJECTIVES: Mobile phones are commonly used by adolescents. The aim of this study
was to clarify associations between duration of mobile phone use and
psychological mood in high school students. METHODS: This cross-sectional study
included 2,785 high school students in Niigata, Japan. A self-administered
questionnaire was used to elicit information on sex, school year, hours of mobile
phone use, psychological mood status, and possible confounders. Psychological
mood outcomes were evaluated with the Mood Inventory, developed and validated in
1994, which includes five subcomponents with total scores ranging from 8 to 32
(higher score indicates stronger feeling): "Tension and excitement," "Refreshing
mood," "Fatigue," "Depressed mood," and "Anxious mood." Analysis of covariance
with Bonferroni's multiple comparison was used to compare mean values among
quartiles of hours of mobile phone use. RESULTS: Among the respondents, mean
mobile phone use per week was 24 (median 18) h. Long-duration mobile phone use
was associated with female students, no participation in sports club activities,
early mobile phone use, and fewer hours spent sleeping (all P < 0.001). Overall
associations between hours of mobile phone use and total scores were significant
for "Depressed mood" (P for trend = 0.005), "Tension and excitement" (P for trend
<0.001), and "Fatigue" (P for trend < 0.001). Total scores for "Depressed mood,"
"Tension and excitement," and "Fatigue" of the fourth quartile (>=33 h/week) of
mobile phone use were significantly higher than for other quartiles (all P <
0.05). CONCLUSIONS: Increased duration of mobile phone use is associated with
unfavorable psychological mood, in particular, a depressed mood. Decreasing
mobile phone use may help maintain appropriate mental health in very long
duration users.
PMID- 24347469
TI - MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is
regulated through two positive feedback loops.
AB - Chondrogenic differentiation of mesenchymal stem cells (MSCs) is regulated by
many factors and signal pathways, including transcription factors such as Sox9
and microRNAs. MiR-335-5p has been previously reported to regulate osteogenic and
adipogenic differentiations of MSCs, but its role in chondrogenic differentiation
of MSC remains unknown. In this study, we found that miR-335-5p and its host gene
Mest are co-expressed and greatly upregulated during mouse MSCs (mMSCs)
chondrogenesis. Overexpression of miR-335-5p in mMSCs increased expression of
chondrogenic marker genes. Molecular mechanism explorations revealed that miR-335
5p targets Daam1 and ROCK1, a set of negative regulators of Sox9; Sox9
downregulates the expression of miR-29a and 29b, both negative regulators of Mest
expression, thus forming a positive loop from miR-335-5p to Sox9 to Mest/miR-335
5p. In addition, miR-335-5p targets DKK1 during mMSC chondrogenic differentiation
to increase beta-catenin/TCF activity, which leads to increased level of Mest
transcription. These data showed miR-335-5p positively regulates MSC
chondrogenesis, and two positive feedback loops are identified for the expression
of miR-335-5p and its host gene Mest during the early phase of mMSC chondrogenic
differentiation.
PMID- 24347470
TI - Definitive radiotherapy for cervical esophageal cancer.
AB - BACKGROUND: The role of contemporary radiotherapy (RT) has not yet been
elucidated, mainly because of the low incidence of cervical esophageal cancer.
The purpose of this study was to analyze the outcome in patients with cervical
esophageal cancer treated with definitive RT. METHODS: A total of 115 patients
with cervical esophageal cancer treated with definitive RT during January 2001
through April 2012 in our center were analyzed. Eighty patients received RT alone
and 35 patients received concurrent chemoradiotherapy with cisplatin administered
either weekly (30 mg/m2) or every 3 weeks (80 mg/m2). RESULTS: The median follow
up time was 17.1 months. For all patients, the overall 2-year local failure-free
survival (LFFS), regional failure-free survival (RFFS), distant failure-free
survival (DFFS), and overall survival (OS) rate was 68.3%, 83.3%, 75.7%, and
47.6%, respectively. CONCLUSION: Definitive RT accomplished a satisfactory local
control rate and contributed to organ preservation for patients with cervical
esophageal cancer. 2015.
PMID- 24347472
TI - Skp2 regulates androgen receptor through ubiquitin-mediated degradation
independent of Akt/mTOR pathways in prostate cancer.
AB - BACKGROUND: The intervention of advanced prostate cancer (PCa) in patients has
been commonly depending on androgen deprivation therapy. Despite of tremendous
research efforts, however, molecular mechanisms on AR regulation remain poorly
understood, particularly for castration resistant prostate cancer (CRPC).
Targeting AR and associated factors is considered an effective strategy in PCa
treatment. METHODS: Human prostate cancer cells were used in this study.
Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or
overexpression of plasmids. Dual luciferase reporter assay was applied for AR
activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and
immunofluorescence were applied to detect the proteins. RESULTS: Our results
demonstrated that Skp2 directly involves the regulation of AR expression through
ubiquitination-mediated degradation. Skp2 interacted with AR protein in PCa
cells, and enforced expression of Skp2 resulted in a decreased level and activity
of AR. By contrast, Skp2 knockdown increased the protein accumulation and
activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent
alterations of PSA level in PCa cells. AR ubiquitination was significantly
increased upon Skp2 overexpression but greatly reduced upon Skp2 knockdown. AR
mutant at K847R abrogated Skp2-mediated ubiquitination of AR. NVP-BEZ235, a dual
PI3K/mTOR inhibitor, remarkably inhibited Skp2 level with a striking elevation of
AR. CONCLUSIONS: The results indicate that Skp2 is an E3 ligase for proteasome
dependent AR degradation, and K847 on AR is the recognition site for Skp2
mediated ubiquitination. Our findings reveal an essential role of Skp2 in AR
signaling.
PMID- 24347473
TI - Preparation of magnetic hydroxyapatite clusters and their application in the
enrichment of phosphopeptides.
AB - A novel strategy for the effective enrichment of phosphopeptides based on
magnetic hydro-xyapatite (HAp) clusters was developed in the current study. The
structure of HAp ensures its probable separation capability, including cation
exchange with P-sites (negatively charged pairs of crystal phosphates), calcium
coordination, anion exchange with C-sites (positively charged pairs of crystal
calcium ions). The prepared magnetic HAp clusters showed good performance on the
efficient enrichment of phosphopeptides from the digestion mixture of beta-casein
and BSA. Compared to commercial HAp particles, the magnetic HAp clusters
exhibited better selectivity toward phosphopeptides. In addition, the use of
magnetic material greatly simplified the enrichment procedure, which avoided the
tedious centrifugation steps in a typical phosphopeptides enrichment protocol.
Finally, the material was successfully applied in the enrichment of
phosphopeptides from human serum. Taken together, the efficient enrichment of the
phosphopeptides by the easily prepared magnetic HAp clusters demonstrated a rapid
and convenient strategy for the purification of phosphopeptides from complex
samples, which may facilitate protein phosphorylation studies.
PMID- 24347477
TI - One step forward in the quest for evidence of the efficacy of cognitive
rehabilitation in multiple sclerosis.
PMID- 24347474
TI - Chelators for copper radionuclides in positron emission tomography
radiopharmaceuticals.
AB - The development of chelating agents for copper radionuclides in positron emission
tomography radiopharmaceuticals has been a highly active and important area of
study in recent years. The rapid evolution of chelators has resulted in highly
specific copper chelators that can be readily conjugated to biomolecules and
efficiently radiolabeled to form stable complexes in vivo. Chelators are not only
designed for conjugation to monovalent biomolecules but also for incorporation
into multivalent targeting ligands such as theranostic nanoparticles. These
advancements have strengthened the role of copper radionuclides in the fields of
nuclear medicine and molecular imaging. This review emphasizes developments of
new copper chelators that have most greatly advanced the field of copper-based
radiopharmaceuticals over the past 5 years.
PMID- 24347478
TI - Clinical commentary.
PMID- 24347475
TI - Transplant versus resection for the management of hepatocellular carcinoma
meeting Milan Criteria in the MELD exception era at a single institution in a
UNOS region with short wait times.
AB - BACKGROUND: Management of hepatocellular carcinoma (HCC) in the Model for End
Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes
were compared for patients undergoing transplant versus resection at a single
institution in a UNOS region with short wait times for organ availability.
METHODS: All patients who underwent resection of HCC from January 2000 to August
2012 and patients who underwent transplant post-January 2006, during the Milan
Criteria (MC)-based MELD exception policy for HCC, were identified. Primary
outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS:
Two hundred fifty-seven patients were analyzed, of whom 131 underwent transplant
and 126 underwent resection. All transplant patients met MC; 45 (36%) resection
patients met MC. Median follow-up time was 30 months. Median wait time to
transplant was 55 days; no patients dropped off the waitlist while awaiting an
organ. Among patients meeting MC, transplant demonstrated significantly greater 5
year OS (65.7% vs. 43.8%; P = 0.005) and RFS (85.3% vs. 22.7%; P < 0.001) versus
resection. For patients with hepatitis C, transplant (n = 87) demonstrated
significantly improved 5-year outcomes compared to patients meeting MC who
underwent resection (n = 21; OS: 63.5% vs. 23.3%; P = 0.001; RFS: 83.5% vs.
23.7%; P < 0.001). CONCLUSION: In a region with short waitlist times for organ
availability, liver transplant is associated with improved survival compared to
resection for HCC within MC and should be considered for all patients meeting MC,
particularly those with hepatitis C.
PMID- 24347479
TI - The role of vascular endothelial growth factor and vascular stability in diseases
of the ear.
AB - OBJECTIVES/HYPOTHESIS: Vascular endothelial growth factor (VEGF) is a critical
mediator of vascular permeability and angiogenesis and likely plays an important
role in cochlear function and hearing. This review highlights the role of VEGF in
hearing loss associated with vestibular schwannomas, otitis media with effusion,
and sensorineural hearing loss. STUDY DESIGN: PubMed literature review. METHODS:
A review of the literature was conducted to determine the role of VEGF in
diseases affecting hearing. RESULTS: Therapeutic efficacy has been demonstrated
for the anti-VEGF agent bevacizumab in vestibular schwannomas, with tumor size
reduction and hearing improvement in patients with neurofibromatosis type 2. The
loss of functional Merlin, the protein product of the nf2 gene, results in a
decrease in expression of the anti-angiogenic protein SEMA3F through a Rac-1
dependent mechanism, allowing VEGF to promote angiogenesis. Bevacizumab may
therefore restore the angiogenic balance through inhibiting the relative increase
in VEGF. Many of the clinical findings of otitis media with effusion can be
reproduced by delivery of recombinant VEGF through transtympanic injection or
submucosal osmotic pump. VEGF receptor inhibitors have been demonstrated to
improve hearing in an animal model of otitis media with effusion. VEGF affects
both the inner ear damage and repair processes in sensorineural hearing loss.
CONCLUSIONS: VEGF has an important role in vestibular schwannomas, otitis media
with effusion, and sensorineural hearing loss.
PMID- 24347480
TI - Response Re: Evaluation of renal function after successful treatment for
unilateral, non-syndromic Wilms tumor.
PMID- 24347481
TI - Nonsurgical intra-operative blood management strategies for total hip
arthroplasty.
AB - The substantial blood loss that can occur during total hip arthroplasty
frequently requires allogeneic transfusions. Both allogeneic transfusions and
post-operative anemia are causes of increased morbidity, cardiovascular risks,
and length of stay. This anemia can also lead to decreased vigor, suboptimal
rehabilitation, and lowered quality of life in patients undergoing total hip
arthroplasty. The aim of this review was to analyze recent evidence on
nonsurgical intra-operative blood management strategies utilized for total hip
arthroplasty. Specifically, we evaluated the use of fibrin sealants,
desmopressin, acute normovolemic hemodilution, hypotensive anesthesia, blood
salvage, and peri-operative normothermia. No single strategy has been shown to
provide superior results over another in reducing the need for allogeneic
transfusions. However, a combination of the above blood management strategies may
further result in reduced blood loss over one strategy. Larger prospective
randomized studies comparing the individual strategies, as well as their
combination, are needed to develop the best algorithm that can be the most
effective and safe for intra-operative blood management in total hip
arthroplasty.
PMID- 24347482
TI - Blood management strategies for total hip arthroplasty in Jehovah's witness
patients.
AB - Total hip arthroplasty is associated with extensive blood loss, which is often
corrected using allogeneic blood transfusions. However, Jehovah's Witnesses often
refuse allogeneic blood transfusions or certain types of autologous blood
transfusions due to their religious beliefs. This may represent a tremendous
challenge for the orthopaedic surgeon and their team. Performing a total hip
arthroplasty on a Jehovah's Witness patient requires a well-trained group of
physicians willing to pre-operatively optimize the patient, attempt to minimize
the blood loss during the surgery, adequately manage the post-operative period,
and be aware of which of the life-saving strategies can be used in these patients
during an emergency situation. Ultimately, physicians should be prepared to deal
with marked blood loss and respect the patients' wishes, values, and beliefs.
This review focuses on studies where primary or revision total hip arthroplasty
was performed in Jehovah's Witness patients. Therefore, we will illustrate that
with a prepared team and an optimized patient, it is potentially quite safe to
perform total hip arthroplasties in Jehovah's Witness patients.
PMID- 24347483
TI - Surgical Intra-operative Blood Management Strategies for Total Hip Arthroplasty.
AB - This section will complement other recent review articles of blood conservation
in total hip arthroplasty. The purpose of this review was to provide a broad
overview, as well as to evaluate the recent evidence on surgical intra-operative
blood management strategies utilized for total hip arthroplasty. In this section,
we specifically evaluated the use of bipolar sealants, patient positioning, wound
compression, computer-assisted surgery, minimally invasive surgical approach, and
cemented versus noncemented prostheses.
PMID- 24347484
TI - Post-operative blood management strategies for total hip arthroplasty.
AB - Total hip arthroplasty is increasing in incidence due to our aging population.
However, this procedure has a high potential for increased blood loss, with
allogeneic blood transfusions commonly used. However, due to potential
transfusion-related risks such as immunosuppression or infections, attempts have
been made to reduce the amount of blood loss and minimize transfusions.
Therefore, our aim was to provide a broad overview of the widely used methods for
reducing post-operative blood loss after total hip arthroplasty. These include
antifibrinolytic agents, autologous blood transfusion drains, avoiding the use of
drains, and modifications in drainage techniques. In addition, lowering the
transfusion threshold is another method used to decrease the rates of allogeneic
blood transfusion. Current evidence suggests that the use of some of these
strategies-either alone, or in combination-may reduce the amount of blood loss
and the need for allogeneic transfusions. However, further research is needed to
create new, more standardized guidelines.
PMID- 24347485
TI - Transforming growth factor-beta1 signaling blockade attenuates gastric cancer
cell-induced peritoneal mesothelial cell fibrosis and alleviates peritoneal
dissemination both in vitro and in vivo.
AB - Peritoneal dissemination is the most frequent metastatic pattern of advanced
gastric cancer and the main cause of death in gastric cancer patients.
Transforming growth factor-beta1 (TGF- beta1), one of the most potent fibrotic
stimuli for human peritoneal mesothelial cells, has been shown to play an
important role in this process. In this study, we investigated the effect of TGF-
beta1 signaling blockade in gastric cancer cell (GCC)-induced human peritoneal
mesothelial cell (HPMC) fibrosis. HPMCs were cocultured with the high TGF- beta1
expressing GCC line SGC-7901 and various TGF- beta1 signaling inhibitors or SGC
7901 transfected with TGF-beta1-specific siRNA. HPMC fibrosis was monitored on
the basis of morphology. Expression of the epithelial cell marker, E-cadherin,
and the mesenchymal marker, alpha-smooth muscle actin (alpha-SMA), was evaluated
by Western blotting and immunofluorescence confocal imaging. GCC adhesion to HPMC
was also assayed. In nude mouse tumor model, the peritoneal fibrotic status was
monitored by immunofluorescent confocal imaging and Masson's trichrome staining;
formation of metastatic nodular and ascites fluid was also evaluated. Our study
demonstrated that GCC expressing high levels of TGF-beta1 induced HMPC fibrosis,
which is characterized by both upregulation of E-cadherin and downregulation of
alpha-SMA. Furthermore, HPMC monolayers fibrosis was reversed by TGF- beta1
signaling blockade. In vivo, the TGF- beta1 receptor inhibitor SB-431542
partially attenuated early-stage gastric cancer peritoneal dissemination (GCPD).
In conclusion, our study confirms the significance of TGFbeta1 signaling blockade
in attenuating GCPD and may provide a therapeutic target for clinical therapy.
PMID- 24347486
TI - Study of circulating antibodies against CD25 and FOXP3 in breast cancer.
AB - Our recent work suggests that circulating levels of anti-CD25 and anti-FOXP3
antibodies were significantly increased in patients with either lung cancer or
esophageal cancer. To confirm if these two autoantibodies are specific for
certain types of malignant tumors, the present work was thus undertaken to
examine an alteration of anti-CD25 and anti-FOXP3 IgG levels in breast cancer. A
total of 152 patients with breast cancer and 112 control subjects were recruited
in this study. The levels of circulating anti-CD25 and anti-FOXP3 IgG antibodies
were tested using an in-house enzyme-linked immunosorbent assay (ELISA).
Student's t test showed no significant differences in the levels of either anti
CD25 IgG or anti-FOXP3 IgG between patients with breast cancer and control
subjects, although patients at stage I had increased levels of anti-CD25 IgG
compared with control subjects (t = 2.11, P = 0.037); there was no significant
association of the anti-FOXP3 IgG levels with stages of breast cancer. In
conclusion, circulating IgG autoantibody to CD25 instead of FOXP3 may be a
potential biomarker for early diagnosis of breast cancer but further
investigation remains needed to replicate this initial finding.
PMID- 24347487
TI - Allergic conditions reduce the risk of glioma: a meta-analysis based on 128,936
subjects.
AB - Many studies have investigated the association between the allergic conditions
and the risk of glioma. However, the evidence is inadequate to draw robust
conclusions because most studies were generally small and conducted in
heterogeneous populations. To shed light on these inconclusive findings, we
conducted a meta-analysis of studies relating the allergic conditions to the risk
of glioma. We identified the relevant studies by searching ISI Web of Science,
PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases, and
Wanfang database by October 2013. We included studies that reported odds ratio
(OR) or hazard ratio (HR) with its 95% confidence interval (CI) for the
association between the allergic condition and the risk of glioma. Eighteen
independent publications, with 9,986 glioma cases and 118,950 controls, were
included. Our results showed that allergic condition was reversely associated
with the risk of glioma (OR = 0.78, 95% CI 0.73-0.83, P < 0.001). The results of
our meta-analysis indicated that allergic conditions significantly reduce the
risk of glioma.
PMID- 24347488
TI - Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute
to bladder cancer risk: a meta-analysis.
AB - Numerous epidemiological studies have been conducted to investigate the
association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn
(rs1799793 G > A) and Lys751Gln (rs13181 A > C) polymorphisms and bladder cancer
risk; however, the conclusions remain controversial. With this in mind, we
performed this meta-analysis with 11 studies including 3,797 cases and 5,094
controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls
for Lys751Gln polymorphism. We searched available literatures from PubMed,
Embase, and CBM databases. Crude odds ratios (ORs) and 95% confidence intervals
(CIs) were calculated to assess the strength of the associations. Moreover, to
validate biological plausibility of our findings, the effects of these two
polymorphisms on XPD gene expression within three ethnicities was determine by
gene expression analysis based on imputed genotypes from HapMap. Overall, the
variant allele of Asp312Asn polymorphism was associated with an increased risk of
bladder cancer (Asn/Asn vs. Asp/Asp: OR = 1.51, 95% CI = 1.19-1.91; Asp/Asn vs.
Asp/Asp: OR = 1.23, 95% CI = 1.12-1.35; recessive model: OR = 1.33, 95% CI = 1.10
1.61; dominant model: OR = 1.32, 95% CI = 1.14-1.52; and allele comparing: OR =
1.26, 95% CI = 1.11-1.42). We found the Lys751Gln was associated with increased
bladder cancer risk only under the recessive model (OR = 1.14, 95% CI = 1.01
1.29). Stratification analyses demonstrated an increased risk for Asians and
hospital-based studies under all genetic models while only under the dominant
model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under
the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn
polymorphism can significantly influence mRNA expression levels among Asians and
Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians.
Despite some limitations, this meta-analysis suggests that polymorphisms in XPD
gene may contribute to bladder cancer susceptibility. These findings need further
validation by large well-designed prospective studies.
PMID- 24347489
TI - Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma
via PI3K/Akt-PAK1 signal pathway.
AB - The objective of this study is to clarify the possible role and mechanism of Axl
in the tumorigenicity and metastasis process of hepatocellular carcinoma. The
mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines
were evaluated by real-time PCR and Western blot analysis. The key factor of
phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling
pathway was studied after Axl expression was downregulated by shRNA. Finally, we
analyzed the expression status of Axl protein expression in hepatocellular
carcinoma tissues and its relationship with the prognosis of hepatocellular
carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines
compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines
resulted in the inhibition of the invasion ability of MHCC97-H cells both in
vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002
or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion.
Finally, the Axl protein expression was positively correlated with
differentiation, lymph node metastasis, and clinical stage in patients with
hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl
can also regulate the metastasis process of hepatocellular carcinoma and may
serve as a new prognostic marker and therapeutic target for treating
hepatocellular carcinoma metastasis.
PMID- 24347490
TI - USP28 is a potential prognostic marker for bladder cancer.
AB - This study was conducted to analyze the expression of the ubiquitin-specific
protease Usp28 and assess its clinical significance in human bladder cancer. mRNA
and protein expression levels of Usp28 were determined by real-time polymerase
chain reaction (PCR) and Western blot in 24 paired bladder cancers and the
adjacent non-cancerous tissues. In addition, the expression of Usp28 protein in
186 bladder cancers was also determined by immunohistochemistry. The relationship
between expression of Usp28 and clinico-pathologic features and prognosis was
finally evaluated. Usp28 was expressed at a higher level in bladder cancers
compared to adjacent non-cancerous tissues at both the mRNA and protein levels in
24 paired samples (all P < 0.01). In immunohistochemical examination, 78 (41.9%)
of 186 cases displayed low Usp28 expression in cancerous tissues, whereas 108
(58.1%) cases displayed high Usp28 expression. In the universal analysis, Usp28
correlated strongly with histopathological grade, clinical stage, tumor number
and recurrence rate (P = 0.0001, 0.0001, 0.0001 and 0.0051, respectively), but
did not correlate with gender or age (P = 0.5588 and 0.6574). After multiple
analysis of the above factors and consideration of confounding factors, tumor
number, histological grade, clinical stage, and recurrence were related to Usp28
expression (P = 0.001, 0.001, 0.001 and 0.001, respectively). Finally, Usp28
expression was indentified as a independent predictors of survival (P = 0.001).
Usp28 protein expression is potentially valuable in prognostic evaluation of
bladder cancer.
PMID- 24347492
TI - Effect of number and ratio of positive lymph nodes in hypopharyngeal cancer.
AB - BACKGROUND: The number and ratio of positive lymph nodes are important prognostic
factors in gastric cancer, but there is little data reported in hypopharyngeal
cancer. METHODS: Medical data from 81 patients with hypopharyngeal cancer
undergoing radical hypopharyngectomy and cervical lymph node dissection were
reviewed. RESULTS: The median survival time was 84, 54, 30, and 13 months in
patients with N0, N1, N2, and N3, respectively, and 84, 51, and 17 months with
positive lymph node ratios (N ratio) 0, <10%, and >10%, respectively. Of the 24
N1 patients, the 20 patients that had an N ratio <10% had a better prognosis than
the 4 patients with an N ratio >10%. Similar data was seen for the N2 patients.
Tumor (T) classification, adjuvant therapy, and N ratio were independent
prognostic factors in multivariate analysis. CONCLUSION: The positive lymph node
ratio is complementary to the current N classification system.
PMID- 24347491
TI - Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical
models of colorectal cancer.
AB - Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall
survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed
to gain further insight into the molecular mechanisms of regorafenib and to
assess its potential in combination therapy. Regorafenib was tested alone and in
combination with irinotecan in patient-derived (PD) CRC models and a murine CRC
liver metastasis model. Mechanism of action was investigated using in vitro
functional assays, immunohistochemistry and correlation with CRC-related
oncogenes. Regorafenib demonstrated significant inhibition of growth-factor
mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3
autophosphorylation, and intracellular VEGFR3 signaling in human umbilical
vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and
also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation
in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of
seven PD xenograft models. Combination of regorafenib with irinotecan
significantly delayed tumor growth after extended treatment in four xenograft
models. Reduced CD31 staining indicates that the antiangiogenic effects of
regorafenib contribute to its antitumor activity. Finally, regorafenib
significantly delayed disease progression in a murine CRC liver metastasis model
by inhibiting the growth of established liver metastases and preventing the
formation of new metastases in other organs. In addition, our results suggest
that regorafenib displays antimetastatic activity, which may contribute to its
efficacy in patients with metastatic CRC. Combination of regorafenib and
irinotecan demonstrated an increased antitumor effect and could provide a future
treatment option for CRC patients.
PMID- 24347493
TI - Differential replication of two porcine parvovirus strains in bovine cell lines
ensues from initial DNA processing and NS1 expression.
AB - Porcine parvovirus (PPV) is a small DNA virus with restricted coding capacity.
The 5 kb genome expresses three major non-structural proteins (NS1, NS2 and SAT),
and two structural proteins (VP1 and VP2). These few viral proteins are
pleiotropic and interact with cellular components throughout viral replication.
In this regard, very few cell lines have been shown to replicate the virus
efficiently. Cell lines were established from a primary culture of bovine cells
that allowed allotropic variants of PPV to be distinguished. Three cell lines
were differentially sensitive to infection by two prototype PPV strains, NADL-2
and Kresse. In the first cell line (D10), infection was restricted early in the
infectious cycle and was not productive. Infection of the second cell line (G11)
was 1000 times less efficient with the NADL-2 strain compared with porcine cells,
while production of infectious virus of the Kresse strain was barely detectable.
Restriction points in these cells were the initial generation of DNA replication
intermediates and NS1 production. Infection with chimeras between NADL-2 and
Kresse showed that residues outside the previously described allotropic
determinant were also partially responsible for the restriction to Kresse
replication in G11 cells. F4 cells were permissive to both strains, although
genome replication and infectious virus production were lower than in the porcine
cells used for comparison. These results highlight the dependent nature of
parvovirus tropism on host factors and suggest that cells from a non-host origin
can fully support a productive infection by both strains.
PMID- 24347494
TI - Comparative ultrastructural characterization of African horse sickness virus
infected mammalian and insect cells reveals a novel potential virus release
mechanism from insect cells.
AB - African horse sickness virus (AHSV) is an arbovirus capable of successfully
replicating in both its mammalian host and insect vector. Where mammalian cells
show a severe cytopathic effect (CPE) following AHSV infection, insect cells
display no CPE. These differences in cell death could be linked to the method of
viral release, i.e. lytic or non-lytic, that predominates in a specific cell
type. Active release of AHSV, or any related orbivirus, has, however, not yet
been documented from insect cells. We applied an integrated microscopy approach
to compare the nanomechanical and morphological response of mammalian and insect
cells to AHSV infection. Atomic force microscopy revealed plasma membrane
destabilization, integrity loss and structural deformation of the entire surface
of infected mammalian cells. Infected insect cells, in contrast, showed no
morphological differences from mock-infected cells other than an increased
incidence of circular cavities present on the cell surface. Transmission electron
microscopy imaging identified a novel large vesicle-like compartment within
infected insect cells, not present in mammalian cells, containing viral proteins
and virus particles. Extracellular clusters of aggregated virus particles were
visualized adjacent to infected insect cells with intact plasma membranes. We
propose that foreign material is accumulated within these vesicles and that their
subsequent fusion with the cell membrane releases entrapped viruses, thereby
facilitating a non-lytic virus release mechanism different from the budding
previously observed in mammalian cells. This insect cell-specific defence
mechanism contributes to the lack of cell damage observed in AHSV-infected insect
cells.
PMID- 24347495
TI - Synthesis of a covalent monolayer sheet by photochemical anthracene dimerization
at the air/water interface and its mechanical characterization by AFM
indentation.
AB - Covalent monolayer sheets in 2 hours: spreading of threefold anthracene-equipped
shape-persistent and amphiphilic monomers at the air/water interface followed by
a short photochemical treatment provides access to infinitely sized, strictly
monolayered, covalent sheets with in-plane elastic modulus in the range of 19
N/m.
PMID- 24347496
TI - Early influences on child satiety-responsiveness: the role of weaning style.
AB - BACKGROUND: Nutrition during infancy may have a long-term impact upon weight gain
and eating style. How infants are introduced to solid foods may be important.
Traditionally, infants are introduced to solid foods via spoon-feeding of purees.
However, baby-led weaning advocates allowing infants to self-feed foods in their
whole form. Advocates suggest this may promote healthy eating styles, but
evidence is sparse. The aim of the current study was to compare child eating
behaviour at 18-24 months between infants weaned using a traditional weaning
approach and those weaned using a baby-led weaning style. METHODS: Two hundred
ninety-eight mothers with an infant aged 18-24 months completed a longitudinal,
self-report questionnaire. In Phase One, mothers with an infant aged 6-12 months
reported breastfeeding duration, timing of solid foods, weaning style (baby-led
or standard) and maternal control, measured using the Child Feeding
Questionnaire. At 18-24 months, post-partum mothers completed a follow-up
questionnaire examining child eating style (satiety-responsiveness, food
responsiveness, fussiness, enjoyment of food) and reported child weight. RESULTS:
Infants weaned using a baby-led approach were significantly more satiety
responsive and less likely to be overweight compared with those weaned using a
standard approach. This was independent of breastfeeding duration, timing of
introduction to complementary foods and maternal control. CONCLUSIONS: A baby-led
weaning approach may encourage greater satiety-responsiveness and healthy weight
gain trajectories in infants. However, the limitations of a self-report
correlational study are noted. Further research using randomized controlled trial
is needed.
PMID- 24347497
TI - Anomalous hypertrophied muscle band in LV mimicking LV mass.
PMID- 24347498
TI - Intramuscular lipoma of the abductor digiti minimi mimicking intramuscular
haemangioma.
AB - Intramuscular lipoma of the foot is rarely reported. We reported a case of
intramuscular lipoma of the abductor digiti minimi mimicking intramuscular
haemangioma in clinical and MR findings.
PMID- 24347499
TI - Strategy for preventing hepatitis B reactivation in patients with resolved
hepatitis B virus infection after rituximab-containing chemotherapy.
PMID- 24347500
TI - After the dawn beckons: a soft awakening to an awful day.
PMID- 24347501
TI - Raptors and primate evolution.
AB - Most scholars agree that avoiding predators is a central concern of lemurs,
monkeys, and apes. However, given uncertainties about the frequency with which
primates actually become prey, the selective importance of predation in primate
evolution continues to be debated. Some argue that primates are often killed by
predators, while others maintain that such events are relatively rare. Some
authors have contended that predation's influence on primate sociality has been
trivial; others counter that predation need not occur often to be a powerful
selective force. Given the challenges of documenting events that can be ephemeral
and irregular, we are unlikely ever to amass the volume of systematic,
comparative data we have on such topics as feeding, social dynamics, or locomotor
behavior. Nevertheless, a steady accumulation of field observations, insight
gained from natural experiments, and novel taphonomic analyses have enhanced
understanding of how primates interact with several predators, especially
raptors, the subject of this review.
PMID- 24347503
TI - Grandmothers and the evolution of human longevity: a review of findings and
future directions.
AB - Women and female great apes both continue giving birth into their forties, but
not beyond. However humans live much longer than other apes do. Even in hunting
and gathering societies, where the mortality rate is high, adult life spans
average twice those of chimpanzees, which become decrepit during their fertile
years and rarely survive them. Since women usually remain healthy through and
beyond childbearing age, human communities include substantial proportions of
economically productive postmenopausal women. A grandmother hypothesis(8-12) may
explain why greater longevity evolved in our lineage while female fertility still
ends at ancestral ages. This hypothesis has implications for the evolution of a
wide array of human features. Here we review some history of the hypothesis,
recent findings, and questions for ongoing research.
PMID- 24347504
TI - From forest fires to fisheries management: anthropology, conservation biology,
and historical ecology.
AB - Human-environmental relationships have long been of interest to a variety of
scientists, including ecologists, biologists, anthropologists, and many others.
In anthropology, this interest was especially prevalent among cultural ecologists
of the 1970s and earlier, who tended to explain culture as the result of techno
environmental constraints. More recently researchers have used historical
ecology, an approach that focuses on the long-term dialectical relationship
between humans and their environments, as well as long-term prehuman ecological
datasets. An important contribution of anthropology to historical ecology is that
anthropological datasets dealing with ethnohistory, traditional ecological
knowledge, and human skeletal analysis, as well as archeological datasets on
faunal and floral remains, artifacts, geochemistry, and stratigraphic analysis,
provide a deep time perspective (across decades, centuries, and millennia) on the
evolution of ecosystems and the place of people in those larger systems.
Historical ecological data also have an applied component that can provide
important information on the relative abundances of flora and fauna, changes in
biogeography, alternations in food webs, landscape evolution, and much more.
PMID- 24347507
TI - Screening of xanthine oxidase inhibitors in complex mixtures using online HPLC
coupled with postcolumn fluorescence-based biochemical detection.
AB - Xanthine oxidase (XO) catalyzes the metabolism of hypoxanthine and xanthine to
uric acid, the overproduction and/or underexcretion of which could cause the
incidence of hyperuricemia such as gout. Herein, the inhibition of XO is
recognized as one of the therapeutic approaches to treat gout. In the present
study, an off-line fluorescence-based microplate method was first developed for
an XO assay in which the enzyme converted pterin to its fluorescent metabolite
isoxanthopterin. Then, a postcolumn continuous XO assay as a means of bioactivity
assessment was coupled to HPLC separation to establish the online HPLC with diode
array detection, biochemical detection, and MS/MS system for the screening of XO
inhibitors. The availability of the online system was first tested with a
positive drug, allopurinol, a well-known XO inhibitor, and subsequent analysis of
Scutellaria baicalensis extract showed that two main bioactive compounds with XO
inhibitory activities were observed, indicating that the developed online system
was applicable to complex mixtures.
PMID- 24347508
TI - Complementary histological and genomic analyses reveal marked differences in the
developmental trajectories of ovaries in Siberian hamsters raised in long- and
short-day lengths.
AB - Siberian hamsters (Phodopus sungorus) delay sexual development when raised in
short-day (SD; 10 hr light: 14 hr dark) conditions, which leads to delayed onset
of estrous cycles and ovulations as compared to females raised in long-day (LD;
16 hr light: 8 hr dark) conditions. In addition to the absence of pre-ovulatory
follicles and corpora lutea, the ovaries of SD-reared Siberian hamsters are
characterized by an abundance of hypertrophied granulosa cells (HGCs) that
surround atretic oocytes. To determine the age at which the histology of LD and
SD ovaries first diverge, including the initial appearance of HGCs in SD
conditions, we examined hamster ovaries histologically at 1, 2, 3, 4, 6, 8, 10,
and 12 weeks of age. After identifying subtle differences in LD and SD ovarian
histology at 4 weeks of age, we searched for differences in ovarian gene
expression at 3 and 8 weeks of age, which correspond to the ages when ovarian
histology do not differ (3 weeks) versus the earliest age when HGCs were observed
(8 weeks). At 3 weeks, only 14 genes were differentially expressed in LD and SD
ovaries, whereas 183 genes were differentially expressed at 8 weeks. Overall, our
findings demonstrate that ovarian development under SD conditions is not simply
arrested at an early stage of LD development, but rather utilizes a developmental
path that is distinct from that used in LD ovaries.
PMID- 24347506
TI - Association of serum uric acid and incident nonspine fractures in elderly men:
the Osteoporotic Fractures in Men (MrOS) study.
AB - Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and
elevated levels may cause arthritis and kidney stones. Conversely, UA also
appears to function as an antioxidant and may protect against the oxidative
stress associated with aging and disease. We performed a prospective fracture
case-cohort study to understand the relation of UA and fracture risk in older men
enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994
men aged 65 years and older attending the baseline MrOS examination, we evaluated
a subgroup 1680 men in a case-cohort study design. The analytic group included
387 men with incident nonspine fractures (73 hip) and a random sample of 1383.
Serum UA was measured in baseline serum samples. Modified proportional hazards
models that account for case-cohort study design were used to estimate the
relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models
were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid
hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score,
frailty, and total. Subjects with incident nonspine fractures were older, had
lower total hip bone mineral density (BMD), and higher serum phosphorus. There
was an 18% decreased risk of nonspine fractures (95% confidence interval [CI]
0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk
of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI
0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate
adjustment. Hip fractures were not significantly associated with UA. Total hip
BMD was significantly higher in the group of men with high UA levels compared
with lower UA levels and increased linearly across quartiles of UA after
multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels
were associated with a reduction in risk of incident nonspine fractures but not
hip fractures and higher hip BMD.
PMID- 24347509
TI - A chemotherapy only therapeutic approach to pediatric Hodgkin lymphoma: AHOPCA LH
1999.
AB - BACKGROUND: AHOPCA is a collaborative group that designs uniform treatment
regimens (protocols) for children diagnosed with cancer in Central America. Based
on a preliminary report from one of the AHOPCA centers, AHOPCA adopted a
treatment regimen to maintain a good event-free survival (EFS) as well as
eliminate radiation therapy from the treatment of children with Hodgkin lymphoma.
PROCEDURE: Newly diagnosed patients with histologically proven Hodgkin lymphoma
were staged according to the Ann Arbor classification and divided into favorable
(stage I, stage IIA, and IIIA) and unfavorable (stage IIB, IIIB, and IV) groups.
Subjects classified as group 1 (favorable) were treated with six 28-day cycles of
chemotherapy (COPP/COPP +/- ABV). Subjects classified as group 2 (unfavorable)
were treated with eight 28-day cycles of COPP/ABV chemotherapy. RESULTS: Of 269
patients registered, 216 were eligible for evaluation. The mean age at diagnosis
was 7.5 years with a male to female ratio of 3.7-1. The predominant histology was
nodular sclerosis (44%) but with a relatively high proportion of mixed
cellularity (35.2%) The EFS at 5 and 10 years was 71% and 68%, respectively.
There was a 14% rate of abandonment of therapy. CONCLUSION: This treatment
regimen for children with Hodgkin lymphoma, when applied as a multi-institutional
regimen, had poorer outcome than our previously reported preliminary data and was
inferior to the EFS reported in high-income countries. The major contributor
adversely affecting EFS in this report is abandonment of therapy. Given these
results, AHOPCA initiated a concerted effort to decrease abandonment of therapy.
PMID- 24347511
TI - Relational coherence in ambiguous and unambiguous relational networks.
AB - Clinical theories often appeal to general cognitive styles in explaining
psychopathology, but without describing in detail how the patterns are formed. In
the present investigation, two experiments were conducted to examine how
individuals respond to ambiguous relational networks. In both experiments, the
participants learned two 3-stimulus networks (A1 LESS THAN B1, A1 GREATER THAN C1
and A2 GREATER THAN B2, C2 LESS THAN A2). Participants were presented with test
trials to examine if they classified the combinatorial relations (B1 <-> C1 and
B2 <-> C2) as SAME or DIFFERENT and as GREATER THAN or LESS THAN. Although the B
C combinatorial relation in Network 1 is derivable in a readily coherent way (B1
GREATER THAN C1 and thus also B1 DIFFERENT C1), in Network 2 the combinatorial
relation is ambiguous. When participants were required to specify the Network 2 B
C relation as either SAME or DIFFERENT, those who chose DIFFERENT, also
consistently chose B2 as either GREATER THAN or LESS THAN C2. Conversely, those
who classified the B-C relation as SAME were inconsistent within themselves in
choosing B2 as GREATER THAN or LESS THAN C2. In Experiment 2, nonarbitrary
multiple exemplar pretraining was used to bias SAME versus DIFFERENT as a
response for ambiguous combinatorial relations. In accord with the pattern seen
in Experiment 1, those biased toward DIFFERENT consistently chose a comparative
relation between B2 and C2 while those biased toward SAME were inconsistent in
their comparative choices. The findings provide support for the importance of
history and coherence in establishing patterns of responding to ambiguous
relational networks, providing a beginning behavioral model of cognitive styles
and errors.
PMID- 24347512
TI - Measurement of the effect of playground surface materials on hand impact forces
during upper limb fall arrests.
AB - Distal radius fractures are common on playgrounds. Yet current guidelines for the
selection of playground surface materials are based only on protection against
fall-related head injuries. We conducted "torso release" experiments to determine
how common playground surface materials affect impact force applied to the hand
during upper limb fall arrests. Trials were acquired for falls onto a rigid
surface, and onto five common playground surface materials: engineered wood
fiber, gravel, mulch, rubber tile, and sand. Measures were acquired for arm
angles of 20 and 40 degrees from the vertical. Playground surface materials
influenced the peak resultant and vertical force (P<.001), but not the peak
horizontal force (P=.159). When compared with the rigid condition, peak resultant
force was reduced 17% by sand (from 1039 to 864 N), 16% by gravel, 7% by mulch,
5% by engineered wood fiber, and 2% by rubber tile. The best performing surface
provided only a 17% reduction in peak resultant force. These results help to
explain the lack of convincing evidence from clinical studies on the
effectiveness of playground surface materials in preventing distal radius
fractures during playground falls, and highlight the need to develop playground
surface materials that provide improved protection against these injuries.
PMID- 24347510
TI - Analysis of CD34+ cell collection using two mobilization regimens for newly
diagnosed multiple myeloma patients reveals the separate impact of mobilization
and collection variables.
AB - Mobilization regimens for CD34+ cells have generally been judged successful based
on the number of cells collected without evaluating mobilization separately from
collection. Using retrospective data for patients who collected CD34+ cells on
Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel
regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed
mobilization and collection variables separately. A significant difference
favoring MVDT-PACE was found in mean CD34+ cells/uL on day 2 of collection and in
mean ratio of CD34+ cells/uL on day 2 to day 1. However, because apheresis
variables and growth factor dose during collection were manipulated to optimize
individual collections, the two regimens were not significantly different when
the mean total CD34+ cells *10(6) /kg collected was compared. Thus, when
evaluating a chemotherapy regimen or new growth factor for mobilization, it is
important to realize that total CD34+ cells collected is dependent on both
mobilization and collection variables.
PMID- 24347513
TI - Diffusion-weighted imaging in head and neck squamous cell carcinomas: a
systematic review.
AB - BACKGROUND: The purpose of this study was for us to review diagnostic accuracy of
diffusion-weighted imaging (DWI) in primary head and neck squamous cell
carcinomas (HNSCCs), detection of metastatic lymph nodes, and recurrences.
METHODS: A systematic review for studies concerning DWI was performed. RESULTS:
Ten studies fulfilled inclusion criteria. All studies showed significant higher
"apparent diffusion coefficient" (ADC) in benign compared to malignant lesions.
ADC thresholds for optimal discrimination varied. In detection of primary HNSCC,
the accuracy of DWI ranged from 66% to 86%. In metastatic lymph nodes, the
accuracy of DWI was 85% to 91% and the negative predictive value (NPV) was higher
than 91%. For recurrences, the accuracy of DWI was 78% to 100% and the NPV ranged
from 77% to 100%. CONCLUSION: DWI showed consistent high accuracy and high NPV.
However, available literature is sparse and varying ADC thresholds were reported.
Compared to current imaging techniques, DWI showed the most potential in lymph
node staging and detection of recurrences.
PMID- 24347514
TI - Comprehensive metagenomic analysis of glioblastoma reveals absence of known virus
despite antiviral-like type I interferon gene response.
AB - Glioblastoma is a deadly malignant brain tumor and one of the most incurable
forms of cancer in need of new therapeutic targets. As some cancers are known to
be caused by a virus, the discovery of viruses could open the possibility to
treat, and perhaps prevent, such a disease. Although an association with viruses
such as cytomegalovirus or Simian virus 40 has been strongly suggested,
involvement of these and other viruses in the initiation and/or propagation of
glioblastoma remains vague, controversial and warrants elucidation. To
exhaustively address the association of virus and glioblastoma, we developed and
validated a robust metagenomic approach to analyze patient biopsies via high
throughput sequencing, a sensitive tool for virus screening. In addition to
traditional clinical diagnostics, glioblastoma biopsies were deep-sequenced and
analyzed with a multistage computational pipeline to identify known or
potentially discover unknown viruses. In contrast to the studies reporting the
presence of viral signatures in glioblastoma, no common or recurring active
viruses were detected, despite finding an antiviral-like type I interferon
response in some specimens. Our findings highlight a discrete and non-specific
viral signature and uncharacterized short RNA sequences in glioblastoma. This
study provides new insights into glioblastoma pathogenesis and defines a general
methodology that can be used for high-resolution virus screening and discovery in
human cancers.
PMID- 24347516
TI - Simultaneous stereoselective detection of chiral fungicides in soil by LC-MS/MS
with fast sample preparation.
AB - An enantioselective method was developed for the simultaneous detection of five
chiral fungicides in soil, including fenbuconazole (1), tetraconazole (2),
nuarimol (3), triticonazole (4), and simeconazole (5) by LC-MS/MS on a chiral
stationary phase of cellulose tris-(3-chloro-4-methylphenylcarbamate) with a
gradient elution. A new multifunctional filter was designed to simplify the
QuEChERS (where QuEChERS is quick, easy, cheap, effective, rugged, and safe)
method by simultaneous cleanup and filtration when the sample extracts were
directly passed through it. Good linearities (R2 > 0.9980) were obtained in the
range 0.005-2.5 mg/L, and the recovery rates were 77.4-103.6% with RSDs of 0.7
12.2% for intraday precision and 1.2-11.0% for interday precision. The LODs and
LOQs for all enantiomers were in the range 0.1-0.2 and 0.25-0.5 MUg/kg,
respectively. The analysis of the incubated soil suggests that this method is
reliable and practical for the stereoselective detection of chiral fungicides.
PMID- 24347515
TI - Scratching the surface: actin' and other roles for the C-terminal Eps15 homology
domain protein, EHD2.
AB - The C-terminal Eps15 homology domain-containing (EHD) proteins participate in
multiple aspects of endocytic membrane trafficking. Of the four mammalian EHD
proteins, EHD2 appears to be the most disparate, both in terms of sequence
homology, and in subcellular localization/function. Since its initial description
as a plasma membrane-associated protein, the precise function of EHD2 has
remained enigmatic. Various reports have suggested roles for EHD2 at the plasma
membrane, within the endocytic transport system, and even in the nucleus. For
example, EHD2 facilitates membrane fusion/repair in muscle cells. Recently the
focus has shifted to the role of EHD2 in regulating caveolae. Indeed, EHD2 is
highly expressed in tissues rich in caveolae, including fat, muscle and blood
vessels. This review highlights cumulative evidence linking EHD2 to actin-rich
structures at the plasma membrane, where the plasma membrane-associated
phospholipid phosphatidylinositol 4,5-bisphosphate controls EHD2 recruitment.
Herein we examine the key pathways where EHD2 might function, and address its
potential involvement in these processes.
PMID- 24347517
TI - The effect of obstructive sleep apnea on olfactory functions.
AB - OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the effect of
obstructive sleep apnea (OSA) on the parameters of olfactory functions (odor
threshold, odor discrimination, and odor identification tests) for orthonasal
olfaction, retronasal olfactory testing, and olfactory bulb (OB) volumes. STUDY
DESIGN: Prospective clinical study. METHODS: This study was carried out in 78
volunteers between the ages of 20 and 60 years. The mean age of the patients was
46 +/- 10.1 years. Patients were divided into three groups according to
polysomnography results: 1) a control group, 2) a mild to moderate OSA group, and
3) a severe OSA group. Clinical features of the participants were evaluated with
the Epworth Sleepiness Scale. Orthonasal and retronasal olfactory testing were
performed with Sniffin' Sticks olfactory testing and retronasal olfactory
testing, respectively. Olfactory bulb volumes were measured by planimetric manual
contouring on magnetic resonance imaging (MRI). RESULTS: The current
investigation produced four major findings: 1) The apnea-hypopnea index had a
significant and strong negative correlation with odor threshold scores and odor
discrimination scores; 2) The apnea-hypopnea index was significantly negatively
correlated with odor identification score and both right and left OB volumes; 3)
retronasal olfactory scores were not significantly affected by OSA; and 4)
continuous O2 saturation had a significant positive correlation on orthonasal
olfactory functions, particularly the odor threshold and discrimination scores.
CONCLUSIONS: This study demonstrated that OSA had significant negative effects on
all orthonasal olfactory tasks, especially on threshold and discrimination. MRI
also revealed volumetric shrinkage of OB volumes.
PMID- 24347518
TI - Predicting distant recurrence in receptor-positive breast cancer patients with
limited clinicopathological risk: using the PAM50 Risk of Recurrence score in
1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine
therapy alone.
AB - BACKGROUND: PAM50 is a 50-gene test that is designed to identify intrinsic breast
cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been
developed to be carried out in qualified routine hospital pathology laboratories.
PATIENTS AND METHODS: One thousand four hundred seventy-eight postmenopausal
women with estrogen receptor (ER)+ early breast cancer (EBC) treated with
tamoxifen or tamoxifen followed by anastrozole from the prospective randomized
ABCSG-8 trial were entered into this study. Patients did not receive adjuvant
chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50
test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR
score were calculated. The primary analysis was designed to test whether the
continuous ROR score adds prognostic value in predicting distant recurrence (DR)
over and above standard clinical variables. RESULTS: In all tested subgroups, ROR
score significantly adds prognostic information to the clinical predictor
(P<0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A
cohort had a significantly lower ROR at 10 years compared with Luminal B
(P<0.0001). Significant and clinically relevant discrimination between low- and
high-risk groups occurred also within all tested subgroups. CONCLUSION(S): The
results of the primary analysis, in combination with recently published results
from the ATAC trial, constitute Level 1 evidence for clinical validity of the
PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A
10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that
additional chemotherapy would improve this outcome-this finding could help to
avoid unwarranted overtreatment. CLINICAL TRIAL NUMBER: ABCSG 8: NCT00291759.
PMID- 24347519
TI - Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment
for early breast cancer: final results of a randomized phase III study (ABCSG
24).
AB - BACKGROUND: This randomized phase III trial compared pathologic complete response
(pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin
docetaxel (ED)+/-capecitabine (C), and evaluated the addition of trastuzumab in
HER2-positive tumors. PATIENTS AND METHODS: Patients with invasive breast cancer
(except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75
mg/m2)+/-C (1000 mg/m2, twice daily, days 1-14). Patients with HER2-positive
disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg
every 3 weeks) or not. Primary end point: pCR rate at the time of surgery.
RESULTS: Five hundred thirty-six patients were randomized to ED (n=266) or EDC
(n=270); 93 patients were further randomized to trastuzumab (n=44) or not (n=49).
pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P=0.027),
and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5%
ED, P=0.212). Rates of axillary node involvement at surgery and breast
conservation were improved with EDC versus ED, but not significantly; the
addition of trastuzumab had no further impact. Hormone receptor status, tumor
size, grade, and C (all P<=0.035) were independent prognostic factors for pCR.
Trastuzumab added to ED+/-C significantly increased the number of serious adverse
events (35 versus 18; P=0.020), mainly due to infusion-related reactions.
CONCLUSION: These findings show that the integration of C into a neoadjuvant
taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment
option, with incorporation of trastuzumab in HER2-positive disease. CLINICAL
TRIAL NUMBER: NCT00309556, www.clinicaltrials.gov.
PMID- 24347520
TI - Efficacy of short-term psychodynamic psychotherapy (STPP) with depressed breast
cancer patients: results of a randomized controlled multicenter trial.
AB - BACKGROUND: There is a lack of trials of psychodynamic treatments of depression
in breast cancer patients. The purpose of this trial was to determine the
efficacy of short-term psychodynamic psychotherapy (STPP) in non-metastatic
breast cancer patients diagnosed with depression, one of the most frequent mental
comorbidities of breast cancer. PATIENTS AND METHODS: In a multicenter
prospective trial, 157 breast cancer patients with comorbid depression were
randomized to either individual STPP (intervention group, N=78) or 'treatment as
usual' (control group, TAU, N=79). As our primary outcome measure, we
hypothesized a higher rate of remission defined as no diagnosis of depression
(Structured Clinical Interview for DSM-IV) and reduction in depression score by
at least 2 points (Hospital Anxiety and Depression Scale, HADS-D) in STPP versus
TAU at treatment termination. Secondary outcomes mainly refer to quality of life
(QoL). RESULTS: In the intention to treat (ITT) analysis, 44% of the STPP group
achieved highly significantly more remission than TAU (23%). STPP treatment
(OR=7.64; P<0.001) was the strongest predictor for remission post-treatment; time
was also significant (OR=0.96; P<0.05). A high effect favoring STPP (d=0.82) was
observed for the HADS-D score post-treatment (secondary outcome). Regarding
further secondary outcomes (QoL), analyses of covariance yielded main effects for
group (favoring STPP with an effect size of at least d=0.5) for global QoL, role,
emotional and social functioning, pain, treatment side-effects, breast symptoms
and upset by hair loss. CONCLUSIONS: STPP is an effective treatment of a broad
range of depressive conditions in breast cancer patients improving depression and
functional QoL. Findings are limited by the drop-out rate (~1/3) and delayed post
treatment assessments. Future trials may consider stepped-care approaches,
tailored to patients' needs and requirements in the acute treatment phase.
PMID- 24347521
TI - Cost-effectiveness of an Internet-based treatment program for stress urinary
incontinence.
AB - AIMS: To perform a deterministic cost-utility analysis, from a 1-year societal
perspective, of two treatment programs for stress urinary incontinence (SUI)
without face-to-face contact: one Internet-based and one sent by post. The
treatments were compared with each other and with no treatment. METHODS: We
performed this economic evaluation alongside a randomized controlled trial. The
study included 250 women aged 18-70, with SUI >= 1 time/week, who were randomized
to 3 months of pelvic floor muscle training via either an Internet-based program
including e-mail support from an urotherapist (n = 124) or a program sent by post
(n = 126). Recruitment was web-based, and participants were self-assessed with
validated questionnaires and 2-day bladder diaries, supplemented by a telephone
interview with a urotherapist. Treatment costs were continuously registered. Data
on participants' time for training, incontinence aids, and laundry were collected
at baseline, 4 months, and 1 year. We also measured quality of life with the
condition-specific questionnaire ICIQ-LUTSqol, and calculated the quality
adjusted life-years (QALYs) gained. Baseline data remained unchanged for the no
treatment option. Sensitivity analysis was performed. RESULTS: Compared to the
postal program, the extra cost per QALY for the Internet-based program ranged
from 200? to 7,253?, indicating greater QALY-gains at similar or slightly higher
costs. Compared to no treatment, the extra cost per QALY for the Internet-based
program ranged from 10,022? to 38,921?, indicating greater QALY-gains at higher,
but probably acceptable costs. CONCLUSION: An Internet-based treatment for SUI is
a new, cost-effective treatment alternative.
PMID- 24347522
TI - A network approach to diagnostic biomarkers in progressive supranuclear palsy.
AB - Diagnosis of progressive supranuclear palsy (PSP) remains challenging because of
the clinical overlap with Parkinson's disease (PD). To date, disease-specific
biomarkers have yet to be identified. In the absence of reliable biomarkers, we
used an integrated network approach to identify genes and related biological
pathways associated with PSP. We tested a highly ranked gene in cellular whole
blood samples from 122 patients enrolled in the Prognostic Biomarker Study.
Biological and functional analysis identified 13 modules related to activation of
leukocytes and lymphocytes, protein dephosphorylation, and phosphatase activity.
Integration of these results with those from microarrays identified ptpn1 as a
potential biomarker for PSP. Assessment of biomarker performance revealed that
ptpn1 could be used to distinguish PSP patients from PD patients with 86%
diagnostic accuracy. Ptpn1 may be a diagnostic marker useful for distinguishing
PSP and PD. Further evaluation in a larger well-characterized prospective study
is warranted.
PMID- 24347523
TI - Extremely obese children respond better than extremely obese adolescents to
lifestyle interventions.
AB - What is already known about this subject Lifestyle intervention is regarded as
therapy of choice in obese children and adolescents. It is unclear whether
extremely obese children and adolescents respond to lifestyle intervention. What
this study adds Extremely obese children respond better than obese children to a
lifestyle intervention. In contrast, most extremely obese adolescents achieved no
weight loss in lifestyle intervention suggesting that other treatment approaches
are needed for them. BACKGROUND: There are conflicting results of treating
extreme obesity in childhood by lifestyle interventions in the literature.
METHODS: We analysed the outcome of a 1-year lifestyle intervention in an
intention-to-treat approach in 1291 children (mean age 11.0 +/- 2.5 years, mean
body mass index [BMI] 27.5 +/- 4.7 kg m(-2), 55.8% female, 62.4% obese, 37.6%
extremely obese (defined by BMI-SDS >2.3) at end of intervention and 1 year
later. RESULTS: The mean BMI-SDS reduction was -0.20 +/- 0.32 at end of
intervention and -0.14 +/- 0.37 1 year after end of intervention compared to
baseline (comparing intervention vs. 1 year later P = 0.010). Extremely obese
children <=10 years demonstrated a significantly greater BMI-SDS reduction than
obese children <=10 years (-0.24 +/- 0.38 vs. -0.16 +/- 0.38, P = 0.021).
Extremely obese adolescents >10 years demonstrated a significantly lower BMI-SDS
reduction compared to obese adolescents >10 years (-0.05 +/- 0.30 vs. -0.15 +/-
0.39, P < 0.001). Comparing the BMI-SDS reduction between obese children <10
years and >10 years revealed no significant difference (P = 0.195) in contrast to
the comparison between extremely obese children <10 years and >10 years (P <
0.001). The same findings were observed in the follow-up period after the end of
intervention. CONCLUSIONS: Our study demonstrated an encouraging effect of
lifestyle intervention in extremely obese children <=10 years at the end of
intervention and 1 year later, but only a limited effect in extremely obese
adolescents >10 years.
PMID- 24347524
TI - Artificial ion channels regulating light-induced ionic currents in
photoelectrical conversion systems.
AB - Artificial ion channels are introduced into a photosystem II photoelectrical
conversion system to mimic the photocurrent regulating of the natural PSII energy
system on the thylakoid membrane. In the composite system, PSII complexes act as
pumps to convert light into currents and artificial ion channels act as valves to
regulate light-induced ionic currents.
PMID- 24347525
TI - How does met regulate the survival/apoptosis balance?
PMID- 24347526
TI - Editorial: Basic and translational research on stimulus-stimulus relations.
PMID- 24347527
TI - Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting
lipolysis.
AB - Long-term cytokine-mediated inflammation is a risk factor for obesity and type 2
diabetes mellitus (T2DM). Our previous studies reveal significant associations
between promoter single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 and
T2DM, as well as between SNPs in genes encoding IL-4/IL-4 receptor and high
density lipoproteins. Our animal study reveals that IL-4 regulates glucose/lipid
metabolism by promoting glucose tolerance and inhibiting lipid deposits. The
above results strongly suggest the involvement of IL-4 in energy homeostasis. In
the present study, we focus on examining the regulatory mechanism of IL-4 to
lipid metabolism. Our results show that IL-4 inhibits adipogenesis by
downregulating the expression of peroxisome proliferator-activated receptor-gamma
and CCAAT/enhancer-binding protein-alpha. Additionally, IL-4 promotes lipolysis
by enhancing the activity and translocation of hormone sensitive lipase (HSL) in
mature adipocytes, which suggests that IL-4 plays a pro-lipolytic role in lipid
metabolism by boosting HSL activity. Our results demonstrate that IL-4 harbors
pro-lipolysis capacity by inhibiting adipocyte differentiation and lipid
accumulation as well as by promoting lipolysis in mature adipocytes to decrease
lipid deposits. The above findings uncover the novel roles of IL-4 in lipid
metabolism and provide new insights into the interactions among cytokine/immune
responses, insulin sensitivity, and metabolism.
PMID- 24347529
TI - Nutrition optimization prior to surgery.
AB - Optimization of metabolic state prior to major surgery leads to improved surgical
outcomes. Nutrition screening protocols should be implemented in the preoperative
evaluation, possibly as part of a bundle. Strategies to minimize hyperglycemia
and insulin resistance by aggressive preoperative nutrition and carbohydrate
loading may promote maintenance of a perioperative anabolic state, improving
healing, reducing complications, and shortening the time to recovery of bowel
function and hospital discharge. Short courses of preoperative immune-modulating
formulas, using combinations of arginine, omega-3 fatty acids, and other
nutrients, have been associated with improved surgical outcomes. These immune
modulating nutrients are key elements of metabolic pathways that promote
attenuation of the metabolic response to stress and improve both wound healing
and immune function. Patients with severe malnutrition and gastrointestinal
dysfunction may benefit from preoperative parenteral nutrition. Continuation of
feeding through the intraoperative period for severely stressed hypermetabolic
patients undergoing nongastrointestinal surgery is another strategy to optimize
metabolic state and reduce prolonged nutrition deficits. In this paper, we review
the importance of preoperative nutrition and strategies for effective
preoperative nutrition optimization.
PMID- 24347528
TI - High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice
by suppressing hepatic inflammation.
AB - Obesity-induced liver inflammation can drive insulin resistance. HDL has anti
inflammatory properties, so we hypothesized that low levels of HDL would
perpetuate inflammatory responses in the liver and that HDL treatment would
suppress liver inflammation and insulin resistance. The aim of this study was to
investigate the effects of lipid-free apoAI on hepatic inflammation and insulin
resistance in mice. We also investigated apoAI as a component of reconstituted
HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our
hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and
administered either saline or lipid-free apoAI. Injections of lipid-free apoAI
twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved
insulin sensitivity associated with decreased systemic and hepatic inflammation;
ii) suppression of hepatic mRNA expression for key transcriptional regulators of
lipogenic gene expression; and iii) suppression of nuclear factor kappaB (NF
kappaB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed
TNFalpha-induced NF-kappaB activation, correlating with decreased NF-kappaB
target gene expression. We conclude that apoAI suppresses liver inflammation in
HFD mice and improves insulin resistance via a mechanism that involves a
downregulation of NF-kappaB activation.
PMID- 24347530
TI - Going with the flow or swimming against the tide: should children with central
venous catheters swim?
AB - Children who require long-term parenteral nutrition (PN) have central venous
catheters (CVCs) in place to allow the safe and effective infusion of life
sustaining fluids and nutrition. Many consider recreational swimming to be a
common part of childhood, but for some, the risk may outweigh the benefit.
Children with CVCs may be at increased risk of exit site, tunnel, and catheter
related bloodstream infections (CRBSIs) if these catheters are immersed in water.
The purpose of this review is to evaluate the current literature regarding the
risk of infection for patients with CVCs who swim and determine if there is
consensus among home PN (HPN) programs on this controversial issue. A total 45
articles were reviewed and 16 pediatric HPN programs were surveyed regarding
swimming and CVCs. Due to the limited data available, a firm recommendation
cannot be made. Recreational water associated outbreaks are well documented in
the general public, as is the presence of human pathogens even in chlorinated
swimming pools. As a medical team, practitioners can provide information and
education regarding the potential risk, but ultimately the decision lies with the
parents. If the parents decide swimming is worth the risk, they are encouraged to
use products designed for this use and to change their child's dressing
immediately after swimming. Due to our experience with a fatal event immediately
after swimming, we continue to strongly discourage patients with CVCs from
swimming. Further large and well-designed studies regarding the risk of swimming
with a CVC are needed to make a strong, evidence-based recommendation.
PMID- 24347531
TI - Quality of life analysis during transition from stationary to portable infusion
pump in home parenteral nutrition patients: a Canadian experience.
AB - BACKGROUND: Quality of life (QOL) of patients receiving home parenteral nutrition
(HPN) may be impacted by device technology. Historically, our HPN patients used
pole-mounted pumps which can hinder activities and affect QOL. METHODS: Patients
receiving HPN with a pole-mounted pump completed Short Form 36 (SF-36(r)) and
pump-specific questionnaires. Patients were then enrolled in a 2-month
prospective crossover open study. Patients were randomized to use a pole-mounted
pump or a portable pump. After 1 month, each arm crossed over. Measurements were
repeated at 4 and 8 weeks. RESULTS: Participants included 5 males, 15 females;
age 52.8 +/- 3.3 (mean +/- SEM) years; 50% had short bowel syndrome; received HPN
for 83.3 +/- 15.9 months; infused HPN over 11.2 +/- 0.3 hours/day; 4.3 +/- 0.4
days/week. Portable pump users scored 53.75 +/- 5.64, 61.25 +/- 6.14, and 40.31
+/- 4.94 in SF-36v2 physical, social, and health vitality, respectively, while
the stationary pump users scored 45.50 +/- 4.82, 55.00 +/- 5.97, and 35.31 +/-
4.63, respectively (NS). They reported ease of movement between rooms (4.11 +/-
0.21 vs 1.44 +/- 0.20; P = .001); when traveling (5.00 +/- 0.00 vs 3.00 +/- 0.45;
P < .02) (1 = very difficult, 5 = very easy); 5.0% were sleep disturbed with the
portable compared to 42.1% with pole-mounted pump (P < .04). Overall, patients
were significantly happier with the portable vs pole-mounted pump (4.53 +/- 0.19
vs 2.68 +/- 0.22; P < .001) (1 = very unhappy, 5 = very happy). CONCLUSION: Our
HPN patients reported improved happiness and satisfaction regarding ease of use
and function with a portable vs pole-mounted pump.
PMID- 24347533
TI - Shank-rearfoot joint coupling with chronic ankle instability.
AB - Chronic ankle instability (CAI) results in longstanding symptoms and subjective
feelings of "giving way" following initial ankle sprain. Our purpose was to
identify differences in joint coupling and variability between shank
internal/external rotation and rearfoot inversion/eversion throughout the gait
cycle of CAI subjects and healthy controls. Twenty-eight young adults
participated (CAI, n = 15, control, n = 13). Kinematics were collected while
walking and jogging on a treadmill. A vector coding method in which direction
(theta) and magnitude of the angle-angle relationship and stride-to-stride
variability (VCV) in shank-rearfoot coupling were calculated. In walking, the CAI
group demonstrated lower theta, indicating a greater proportion of rearfoot-to
shank motion, compared with the control group in early and late swing. The CAI
group had higher magnitude, indicating greater combined motion between the two
segments, in early swing, but lower magnitude, indicating less combined motion,
during late swing. The CAI group also had lower VCV measures, indicating less
stride-to-stride variability during stance. In jogging, the CAI group had lower
theta measures than the control group during stance and swing. Differences in
shank-rearfoot coupling of the CAI group may be related to changes in
sensorimotor control and lead to further instances of instability.
PMID- 24347532
TI - Serum prognostic biomarkers in head and neck cancer patients.
AB - OBJECTIVES/HYPOTHESIS: A reliable estimate of survival is important as it may
impact treatment choice. The objective of this study is to identify serum
autoantibody biomarkers that can be used to improve prognostication for patients
affected with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN:
Prospective cohort study. METHODS: A panel of 130 serum biomarkers, previously
selected for cancer detection using microarray-based serological profiling and
specialized bioinformatics, were evaluated for their potential as prognostic
biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A
biomarker was considered positive if its reactivity to the particular patient's
serum was greater than one standard deviation above the mean reactivity to sera
from the other 118 patients, using a leave-one-out cross-validation model.
Survival curves were estimated according to the Kaplan-Meier method, and
statistically significant differences in survival were examined using the log
rank test. Independent prognostic biomarkers were identified following analysis
using multivariate Cox proportional hazards models. RESULTS: Poor overall
survival was associated with African Americans (hazard ratio [HR] for death =
2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR =
2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI:
2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates
(race and stage), six of the 130 markers evaluated were found to be independent
prognosticators of overall survival. CONCLUSIONS: The results shown here are
promising and demonstrate the potential use of serum biomarkers for
prognostication in HNSCC patients. Further clinical trials to include larger
samples of patients across multiple centers may be warranted.
PMID- 24347534
TI - Effects of 3-hydroxyflavone on the cellular and molecular characteristics of
bovine embryos produced by somatic-cell nuclear transfer.
AB - This study aimed to investigate the effects of 3-hydroxyflavone, a natural
antioxidant pigment enriched in vegetables, on the developmental cellular and
molecular characteristics of bovine somatic-cell nuclear transfer (SCNT) embryos.
There were no significant differences in the cleavage rate at 48 hr of culture or
in the inner cell mass (ICM)-to-trophectoderm (TE) ratio between 3-hydroxyflavone
addition and untreated (control) groups (P > 0.05). 3-hydroxyflavone (20 uM) did,
however, increase the cleavage rate at 24 hr of culture and the blastocyst
formation rate on Days 6 and 7 (P < 0.05); decrease the levels of intracellular
reactive oxygen species in two-, four-, and eight-cell stage embryos (P < 0.05);
increase H3K9ac levels in two- and four-cell stages (P < 0.05); increase the
total cell number; and decrease the apoptosis index in Day-7 blastocysts.
Furthermore, the addition of 3-hydroxyflavone resulted in lower expression of the
stress-related gene HSP70.1 and pro-apoptotic gene BAX, as well as higher
expression of the anti-apoptotic gene BCL-xL and pluripotency-related genes OCT4
and SOX2 in Day-7 blastocysts produced by SCNT (P < 0.05). The addition of 3
hydroxyflavone during in vitro culture thus exerted beneficial effects on
preimplantation development of bovine SCNT embryos both at the cellular and
molecular levels.
PMID- 24347535
TI - Thermosensitive molecularly imprinted hydrogel cross-linked with N-malely
chitosan for the recognition and separation of BSA.
AB - A novel temperature-sensitive molecularly imprinted hydrogel composed of N
isopropylacrylamide and acrylamide has been prepared by using free-radical
polymerization and was cross-linked by modified water-soluble N-maley chitosan in
aqueous solution. BSA (pI 4.9, MW 66.0 kDa) was used as the template protein. The
produced hydrogels were characterized by environmental SEM to reveal the
microcosmic morphology. A microporous structure was only found in the imprinted
hydrogel, while no obvious microporous structure was found in nonimprinted
hydrogels. The lower critical solution temperature of the hydrogels was 34
degrees C, and the optimal binding conditions were tested, namely, the adsorption
equilibrium time of 6 h and initial BSA concentration of 1.0 mg/mL. The
adsorption capacity Qmax was determined by Langmuir isotherm plots and was 5.72
mg/g for imprinted hydrogel and 1.18 mg/g for nonimprinted hydrogels. A
separation factor (beta) of 4 was obtained when bovine hemoglobin (pI 6.9, MW
64.0 kDa) was selected as the particular reference protein. Molecular weights and
pIs were chosen to investigate the selectivity of the hydrogels. It was shown
that the shape memory and the size effect were the major factors for the
recognition. This imprinted hydrogel was used to specifically adsorb the BSA from
the protein mixture.
PMID- 24347536
TI - Activation of hedgehog signaling during fracture repair enhances osteoblastic
dependent matrix formation.
AB - Fracture repair is a well orchestrated process involving various cell types and
signaling molecules. The hedgehog signaling pathway is activated in chondrocytes
during fracture repair and is known to regulate chondrogenesis however, its role
in osteoblasts during injury is yet unknown. In this study we observed tibial
fracture repair in mice in which hedgehog signaling was modulated through genetic
alterations of the pathway activator, smoothened. Levels of the hedgehog target
genes Gli1 and Ptch1 in wildtype mice were upregulated in fracture calluses
throughout the repair process. Forced activation of the hedgehog pathway in
ubiquitous fashion resulted in increased matrix deposition in the fracture
callus. Interestingly, inhibition in chondrocytes did not alter the fracture
repair phenotype, while activation of hedgehog in osteoblasts was a requirement
for normal fracture repair. In vitro, transcript levels of Gli1 and Ptch1 were
elevated during osteoblastogenesis. Activation of hedgehog signaling positively
affected osteoblastic differentiation and mineralization as detected using
alkaline phosphatase and Von Kossa staining and Alp and Col1 expression. Here we
show that the hedgehog signaling pathway plays a critical role in osteoblasts
during fracture repair: inhibition of the pathway in osteoblasts leads to
decreased matrix at the fracture site while activation increased matrix
deposition.
PMID- 24347537
TI - Survival outcomes of patients with temporal bone squamous cell carcinoma with
different invasion patterns.
AB - BACKGROUND: The correlation between the survival rate and various invasion
patterns of patients with temporal bone squamous cell carcinoma (SCC) is unclear.
This study was performed to compare the survival outcomes of these patients to
disclose the correlation. METHODS: The cases of 39 patients with temporal bone
SCC who underwent surgery between January 2004 and December 2012 were reviewed.
RESULTS: The 2-year overall survival rate was 56.9%, and it was 22.3% for
patients with stage IV disease, and 100% for patients with stage I-III disease.
Patients with parotid invasion (n = 11), temporomandibular joint (TMJ)
involvement (n = 8), and middle ear surgery (n = 7) before temporal bone
malignancies were diagnosed had poor survival with statistical difference.
CONCLUSION: Patients with parotid gland, TMJ involvement, and previous middle ear
surgery for chronic otitis media had poor outcomes.
PMID- 24347538
TI - New methods of preventing neurodegeneration? Lessons from prion diseases.
PMID- 24347540
TI - Two-dimensional Si nanosheets with local hexagonal structure on a MoS(2) surface.
AB - The structural and electronic properties of a Si nanosheet (NS) grown onto a MoS2
substrate by means of molecular beam epitaxy are assessed. Epitaxially grown Si
is shown to adapt to the trigonal prismatic surface lattice of MoS2 by forming
two-dimensional nanodomains. The Si layer structure is distinguished from the
underlying MoS2 surface structure. The local electronic properties of the Si
nanosheet are dictated by the atomistic arrangement of the layer and unlike the
MoS2 hosting substrate they are qualified by a gap-less density of states.
PMID- 24347539
TI - Binge eating, binge eating disorder and loss of control eating: effects on weight
outcomes after bariatric surgery.
AB - There is increasing evidence that patients who have problems with binge eating
(BE) or BE disorder (BED) are quite common among the severely obese, including
bariatric surgery candidates. The literature suggests that in many cases such
eating behaviours improve after bariatric surgery, although this is not uniformly
true. The current paper reviews the data on the development of BE, BED and loss
of control (LOC) eating after bariatric surgery and the impact of these problems
on long-term weight outcome. A search was made of various databases regarding
evidence of BE, BED and LOC eating post-operatively in bariatric surgery
patients. The data extracted from the literature suggests that 15 research
studies have now examined this question. Fourteen of the available 15 studies
suggest that the development of problems with BE, BED or LOC eating post
bariatric surgery is associated with less weight loss and/or more weight regain
post-bariatric surgery. These data suggests that it is important to identify
individuals at high risk for these problems, to follow them post-operatively,
and, if appropriate interventions can be developed if such behaviours occur in
order to maximize weight loss outcomes.
PMID- 24347541
TI - Characterizing the nature of home care work and occupational hazards: a
developmental intervention study.
AB - BACKGROUND: Home care (HC) aide is the fastest growing occupation, yet job
hazards are under-studied. This study documents the context of HC aide work,
characterizes occupational safety and health (OSH) hazards, and identifies
preventive interventions using qualitative methods. METHODS: We conducted 12
focus groups among aides and 26 in-depth interviews comprising 15 HC agency,
union, and insurance company representatives as well as 11 HC recipients in
Massachusetts. All focus groups and interviews were audio-recorded, transcribed,
and coded with NVIVO software. RESULTS: Major OSH concerns were musculoskeletal
disorders from client care tasks and verbal abuse. Performing tasks beyond
specified job duties may be an OSH risk factor. HC aides' safety and clients'
safety are closely linked. Client handling devices, client evaluation, care plan
development, and training are key interventions for both aides' and clients'
safety. CONCLUSIONS: Promoting OSH in HC is essential for maintaining a viable
workforce.
PMID- 24347542
TI - Labeling of the pathogenic bacterium Staphylococcus aureus with gold or ferric
oxide-core nanoparticles highlights new capabilities for investigation of host
pathogen interactions.
AB - Throughout the world, infections caused by bacteria such as Staphylococcus aureus
are a major cause of morbidity and mortality. In order to gain some understanding
of the complicated physiological link between host and pathogen, modern
techniques such as confocal microscopy and sophisticated OMICs technologies are
suitable. However, labeling of pathogens such as S. aureus with green fluorescent
protein, for example, or the generation of a reliable antibody, which are
prerequisites for the application of reproducible isolation techniques, does not
always succeed. Here, we present a universal approach for monitoring pathogen
traffic after internalization into host cells by fluorescence microscopy and for
isolation of bacteria from host-pathogen interaction assays using gold or ferric
oxide-core, poly(vinyl alcohol) coated, and fluorescence-labeled nanoparticles
(NP). The incubation of S. aureus HG001 with those NP had only minor effects on
the bacterial growth in vitro. Quantitative proteome analysis after 24 h of NP
incubation revealed that presence of NP provoked only marginal changes in the
proteome pattern. The method presented enabled us to investigate the behavior of
S. aureus HG001 during infection of S9 human epithelial cells by means of
fluorescence microscopy and proteomics using magnetic separation or cell sorting.
PMID- 24347543
TI - Spatial dilemmas of diffusible public goods.
AB - The emergence of cooperation is a central question in evolutionary biology.
Microorganisms often cooperate by producing a chemical resource (a public good)
that benefits other cells. The sharing of public goods depends on their diffusion
through space. Previous theory suggests that spatial structure can promote
evolution of cooperation, but the diffusion of public goods introduces new
phenomena that must be modeled explicitly. We develop an approach where colony
geometry and public good diffusion are described by graphs. We find that the
success of cooperation depends on a simple relation between the benefits and
costs of the public good, the amount retained by a producer, and the average
amount retained by each of the producer's neighbors. These quantities are derived
as analytic functions of the graph topology and diffusion rate. In general,
cooperation is favored for small diffusion rates, low colony dimensionality, and
small rates of decay of the public good. DOI:
http://dx.doi.org/10.7554/eLife.01169.001.
PMID- 24347544
TI - Bone morphogenic protein signalling suppresses differentiation of pluripotent
cells by maintaining expression of E-Cadherin.
AB - Bone morphogenic protein (BMP) signalling contributes towards maintenance of
pluripotency and favours mesodermal over neural fates upon differentiation, but
the mechanisms by which BMP controls differentiation are not well understood. We
report that BMP regulates differentiation by blocking downregulation of Cdh1, an
event that accompanies the earliest stages of neural and mesodermal
differentiation. We find that loss of Cdh1 is a limiting requirement for
differentiation of pluripotent cells, and that experimental suppression of Cdh1
activity rescues the BMP-imposed block to differentiation. We further show that
BMP acts prior to and independently of Cdh1 to prime pluripotent cells for
mesoderm differentiation, thus helping to reinforce the block to neural
differentiation. We conclude that differentiation depends not only on exposure to
appropriate extrinsic cues but also on morphogenetic events that control
receptivity to those differentiation cues, and we explain how a key pluripotency
signal, BMP, feeds into this control mechanism. DOI:
http://dx.doi.org/10.7554/eLife.01197.001.
PMID- 24347545
TI - A new topology of the HK97-like fold revealed in Bordetella bacteriophage by
cryoEM at 3.5 A resolution.
AB - Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping
cough. Its diversity-generating retroelement (DGR) provides a naturally occurring
phage-display system, but engineering efforts are hampered without atomic
structures. Here, we report a cryo electron microscopy structure of the BPP-1
head at 3.5 A resolution. Our atomic model shows two of the three protein folds
representing major viral lineages: jellyroll for its cement protein (CP) and HK97
like ('Johnson') for its major capsid protein (MCP). Strikingly, the fold
topology of MCP is permuted non-circularly from the Johnson fold topology
previously seen in viral and cellular proteins. We illustrate that the new
topology is likely the only feasible alternative of the old topology. beta-sheet
augmentation and electrostatic interactions contribute to the formation of non
covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97
chainmail. Despite these complex interactions, the termini of both CP and MCP are
ideally positioned for DGR-based phage-display engineering. DOI:
http://dx.doi.org/10.7554/eLife.01299.001.
PMID- 24347546
TI - c-di-GMP heterogeneity is generated by the chemotaxis machinery to regulate
flagellar motility.
AB - Individual cell heterogeneity is commonly observed within populations, although
its molecular basis is largely unknown. Previously, using FRET-based microscopy,
we observed heterogeneity in cellular c-di-GMP levels. In this study, we show
that c-di-GMP heterogeneity in Pseudomonas aeruginosa is promoted by a specific
phosphodiesterase partitioned after cell division. We found that subcellular
localization and reduction of c-di-GMP levels by this phosphodiesterase is
dependent on the histidine kinase component of the chemotaxis machinery, CheA,
and its phosphorylation state. Therefore, individual cell heterogeneity in c-di
GMP concentrations is regulated by the activity and the asymmetrical inheritance
of the chemotaxis organelle after cell division. c-di-GMP heterogeneity results
in a diversity of motility behaviors. The generation of diverse intracellular
concentrations of c-di-GMP by asymmetric partitioning is likely important to the
success and survival of bacterial populations within the environment by allowing
a variety of motility behaviors. DOI: http://dx.doi.org/10.7554/eLife.01402.001.
PMID- 24347547
TI - The genomic landscape of meiotic crossovers and gene conversions in Arabidopsis
thaliana.
AB - Knowledge of the exact distribution of meiotic crossovers (COs) and gene
conversions (GCs) is essential for understanding many aspects of population
genetics and evolution, from haplotype structure and long-distance genetic
linkage to the generation of new allelic variants of genes. To this end, we
resequenced the four products of 13 meiotic tetrads along with 10 doubled
haploids derived from Arabidopsis thaliana hybrids. GC detection through short
reads has previously been confounded by genomic rearrangements. Rigid filtering
for misaligned reads allowed GC identification at high accuracy and revealed an
~80-kb transposition, which undergoes copy-number changes mediated by meiotic
recombination. Non-crossover associated GCs were extremely rare most likely due
to their short average length of ~25-50 bp, which is significantly shorter than
the length of CO-associated GCs. Overall, recombination preferentially targeted
non-methylated nucleosome-free regions at gene promoters, which showed
significant enrichment of two sequence motifs. DOI:
http://dx.doi.org/10.7554/eLife.01426.001.
PMID- 24347548
TI - Frizzled3 controls axonal development in distinct populations of cranial and
spinal motor neurons.
AB - Disruption of the Frizzled3 (Fz3) gene leads to defects in axonal growth in the
VII(th) and XII(th) cranial motor nerves, the phrenic nerve, and the dorsal motor
nerve in fore- and hindlimbs. In Fz3(-/-) limbs, dorsal axons stall at a precise
location in the nerve plexus, and, in contrast to the phenotypes of several other
axon path-finding mutants, Fz3(-/-) dorsal axons do not reroute to other
trajectories. Affected motor neurons undergo cell death 2 days prior to the
normal wave of developmental cell death that coincides with innervation of muscle
targets, providing in vivo evidence for the idea that developing neurons with
long-range axons are programmed to die unless their axons arrive at intermediate
targets on schedule. These experiments implicate planar cell polarity (PCP)
signaling in motor axon growth and they highlight the question of how PCP
proteins, which form cell-cell complexes in epithelia, function in the dynamic
context of axonal growth. DOI: http://dx.doi.org/10.7554/eLife.01482.001.
PMID- 24347549
TI - A serine sensor for multicellularity in a bacterium.
AB - We report the discovery of a simple environmental sensing mechanism for biofilm
formation in the bacterium Bacillus subtilis that operates without the
involvement of a dedicated RNA or protein. Certain serine codons, the four TCN
codons, in the gene for the biofilm repressor SinR caused a lowering of SinR
levels under biofilm-inducing conditions. Synonymous substitutions of these TCN
codons with AGC or AGT impaired biofilm formation and gene expression.
Conversely, switching AGC or AGT to TCN codons upregulated biofilm formation.
Genome-wide ribosome profiling showed that ribosome density was higher at UCN
codons than at AGC or AGU during biofilm formation. Serine starvation
recapitulated the effect of biofilm-inducing conditions on ribosome occupancy and
SinR production. As serine is one of the first amino acids to be exhausted at the
end of exponential phase growth, reduced translation speed at serine codons may
be exploited by other microbes in adapting to stationary phase. DOI:
http://dx.doi.org/10.7554/eLife.01501.001.
PMID- 24347550
TI - Ready, set, differentiate!
AB - The expression of E-Cadherin, a protein best known for its role in cell adhesion,
regulates the onset of embryonic differentiation.
PMID- 24347551
TI - How to survive a nerve-wracking journey.
AB - When the axons that carry signals to muscles are growing, they rely on help from
Frizzled3-a protein that is known to perform a number of other important
functions in cells-to reach their final destination.
PMID- 24347552
TI - Gene expression profiling in true interval breast cancer reveals overactivation
of the mTOR signaling pathway.
AB - BACKGROUND: The development and progression of true interval breast cancers
(tumors that truly appear after a negative screening mammogram) is known to be
different from screen-detected cancers. However, the worse clinical behavior of
true interval cancers is not fully understood from a biologic basis. We described
the differential patterns of gene expression through microarray analysis in true
interval and screen-detected cancers. METHODS: An unsupervised exploratory gene
expression profile analysis was performed on 10 samples (true interval cancers =
5; screen-detected cancers = 5) using Affymetrix Human Gene 1.0ST arrays and
interpreted by Ingenuity Pathway Analysis. Differential expression of selected
genes was confirmed in a validation series of 91 tumors (n = 12; n = 79) by
immunohistochemistry and in 24 tumors (n = 8; n = 16) by reverse transcription
quantitative PCR (RT-qPCR), in true interval and screen-detected cancers,
respectively. RESULTS: Exploratory gene expression analysis identified 1,060
differentially expressed genes (unadjusted P < 0.05) between study groups. On the
basis of biologic implications, four genes were further validated: ceruloplasmin
(CP) and ribosomal protein S6 kinase, 70 kDa, polypeptide 2 (RPS6KB2), both
upregulated in true interval cancers; and phosphatase and tensin homolog (PTEN)
and transforming growth factor beta receptor III (TGFBR3), downregulated in true
interval cancers. Their differential expression was confirmed by RT-qPCR and
immunohistochemistry, consistent with mTOR pathway overexpression in true
interval cancers. CONCLUSIONS: True interval and screen-detected cancers show
differential expression profile both at gene and protein levels. The mTOR
signaling is significantly upregulated in true interval cancers, suggesting this
pathway may mediate their aggressiveness. IMPACT: Linking epidemiologic factors
and mTOR activation may be the basis for future personalized screening strategies
in women at risk of true interval cancers.
PMID- 24347553
TI - Muscle contributions to elbow joint rotational stiffness in preparation for
sudden external arm perturbations.
AB - Understanding joint stiffness and stability is beneficial for assessing injury
risk. The purpose of this study was to examine joint rotational stiffness for
individual muscles contributing to elbow joint stability. Fifteen male
participants maintained combinations of three body orientations (standing,
supine, sitting) and three hand preloads (no load, solid tube, fluid filled tube)
while a device imposed a sudden elbow extension. Elbow angle and activity from
nine muscles were inputs to a biomechanical model to determine relative
contributions to elbow joint rotational stiffness, reported as percent of total
stiffness. A body orientation by preload interaction was evident for most muscles
(P<.001). Brachioradialis had the largest change in contribution while standing
(no load, 18.5%; solid, 23.8%; fluid, 26.3%). Across trials, the greatest
contributions were brachialis (30.4+/-1.9%) and brachioradialis (21.7+/-2.2%).
Contributions from the forearm muscles and triceps were 5.5+/-0.6% and 9.2+/
1.9%, respectively. Contributions increased at time points closer to the
perturbation (baseline to anticipatory), indicating increased neuromuscular
response to resist rotation. This study quantified muscle contributions that
resist elbow perturbations, found that forearm muscles contribute marginally and
showed that orientation and preload should be considered when evaluating elbow
joint stiffness and safety.
PMID- 24347554
TI - Separation of xanthines in hydro-organic and polar-organic elution modes on a
titania stationary phase.
AB - Hydrophilic interaction LC was investigated in hydro-organic and nonaqueous
elution modes on a titania column by using a set of N-methyl xanthines as neutral
polar probes. To get information regarding the mechanisms that are behind the
discrimination of these analytes in hydrophilic interaction, we focused our study
on the type and amount of organic modifier as a critical yet rarely explored
mobile phase parameter. Several alcohols such as methanol, ethanol, and
isopropanol were studied as substitutes to acetonitrile in hydro-organic elution
mode. Compared to silica, the investigation of the eluotropic series of these
alcohols on titania highlighted a different implication in the retention
mechanism of the xanthine derivatives. At low amounts of protic solvents, the
adsorption mainly characterized the retention of analytes on bare silica; whereas
mixed interactions including adsorption and ligand exchange were identified on
native titania. To investigate the peculiar behavior of alcohols on the metal
oxide, methanol, ethanol, and ethylene glycol were tested in replacement of water
in polar-organic elution mode. Distinctive effects on the chromatographic
retention and selectivity of xanthines were noticed for the dihydric alcohol,
which was found to be a stronger eluting component than water on titania.
PMID- 24347555
TI - Airways obstruction and pulmonary capillary blood volume in children with sickle
cell disease.
PMID- 24347556
TI - The influence of intensity and duration of a painful conditioning stimulation on
conditioned pain modulation in volunteers.
AB - BACKGROUND AND METHOD: The aim was to investigate influence from variations in
intensity of a painful conditioning stimulation (CS) on early (0-6 min) and
prolonged (6-12 min) conditioned pain modulation (CPM) in volunteers during
concurrent exposure to test stimuli (TS). CS was applied to either forearm using
painful heat with an intensity of 2/10 and 5/10, respectively, rated on a 0-10
numerical pain rating scale. At a second session, CS with an intensity of 7/10
was applied to the arm using a tourniquet. Threshold and suprathreshold painful
heat and pressure as well as painful repeated monofilament pricking (RMP) were
assessed as TS. RESULTS: Regardless of TS, there was no significant difference in
the magnitude of CPM within the same stimulus modality during the various
intensities and phases of the CS. Significant modulation of heat pain thresholds
(HPTs) was found during the early phase at 5/10 and 7/10, but not at 2/10. Only
at 5/10 the prolonged CS resulted in a significant additional increase in HPT.
During the early CS phase, CPM of suprathreshold heat pain was found at 2/10 and
5/10. The prolonged CS resulted in a significant additional temperature increase
at 5/10. Only during the early phase significant CPM of pressure pain thresholds
were found for all three pain intensities in conjunction with a significant CPM
of suprathreshold pressure pain at 5/10. There was no CPM of RMP. CONCLUSION: The
CS intensity and the duration of CPM modulated pain sensitivity differentially
across TS modalities.
PMID- 24347557
TI - Injury classification agreement in linked Bureau of Labor Statistics and Workers'
Compensation data.
AB - BACKGROUND: Estimates of select occupational injuries and illnesses often differ
across data sources. We explored agreement in injury classifications and the
impact of differences on case estimates among records reported to multiple data
sources. METHODS: We linked cases reported in the Bureau of Labor Statistics
(BLS) annual Survey of Occupational Injuries and Illnesses (SOII) to Washington
State workers' compensation (WC) claims and evaluated agreement in injury
characteristics coded in each data source according to the same occupational
injury and illness classification system. RESULTS: Agreement between data sources
was greatest for body part and lowest for event or exposure. Agreement on nature
of injury varied by condition. WC-assigned injury codes estimated 94% more
amputations than SOII-assigned codes while SOII-assigned codes estimated 34% more
work-related MSD cases. CONCLUSIONS: Accounting for classification differences
may improve case ascertainment within individual data sources and help align
injury and illness estimates derived from different data sources.
PMID- 24347558
TI - Editorial: Epidemiologic approaches to women's health.
PMID- 24347559
TI - Transcriptomic study of the red palm weevil Rhynchophorus ferrugineus
embryogenesis.
AB - The red palm weevil (RPW), Rhynchophorus ferrugineus (Coleoptera: Curculionidae),
is an invasive, concealed and destructive tissue borer, and it becomes a lethal
pest of the palm family of plants and has been reported to attack 20 palm species
around the globe. Here we report a systematic transcriptomic study on
embryogenesis of RPW, where we analyze the transcriptomes across five
developmental stages of RPW embryogenesis, involving four embryonic stages (E1,
E2, E3 and E4) and one larval stage (L1). Using the RNA-seq and next-generation
platforms, we generated 80 to 91 million reads for each library and assemble 22
532 genes that are expressed at different embryonic stages. Among the total
transcripts from the five embryonic development stages, we found that 30.45 % are
differentially expressed, 10.10 % show stage-specificity and even a larger
fraction, 62.88 %, exhibit constitutive expression in all the stages. We also
analyzes the expression dynamics of several conserved signaling pathways (such as
Hedgehog, JAK-STAT, Notch, TGF-beta, Ras/MAPK and Wnt), as well as key
developmental genes, including those related to apoptosis, axis formation, Hox
complex, neurogenesis and segmentation. The datasets provide an essential
resource for gene annotation and RPW functional genomics, including studies by
using tools and concepts from multiple disciplines, such as development,
physiology, biochemistry, molecular biology and genetics.
PMID- 24347560
TI - DENND1B gene variants associate with elevated exhaled nitric oxide in healthy
high-risk neonates.
AB - RATIONALE OF THE STUDY: Increased neonatal fraction of exhaled nitric oxide
(FeNO) is associated with lung symptoms early in life, while predictors of
neonatal FeNO levels are unknown. The objective of this study was to investigate
perinatal and genetic predictors of FeNO in healthy at-risk neonates. METHODS:
FeNO was measured during sedation by single-breath and tidal-breathing techniques
in 253 one-month-old neonates from the Copenhagen Prospective Study on Asthma in
Childhood (COPSAC2000 ) birth cohort. The risk factor analyses included genetic
variants in DENND1B, Filaggrin, and ORMDL3; anthropometrics; demographics;
socioeconomics; paternal atopy; maternal smoking, and mother's consumption of
paracetamol and antibiotics during 3rd trimester; and neonatal bacterial airway
colonization. RESULTS: FeNO values measured by the single-breath versus tidal
breathing technique yielded slightly higher values (median, 21.0 ppb; range, 2.0
74.0 ppb vs. 16.0 ppb; 1.0-67.0 ppb; P<0.0001) with increasing differences
conditional on increasing FeNO values (P<0.0001). The multivariable analysis
including all risk factors showed that the DENND1B rs2786098 C allele was
associated with increasing levels of FeNO (additive model; +2.30 ppb per C
allele; 95% CI, 0.10-5.00 ppb; P=0.04) and that children of atopic fathers had
elevated FeNO (+2.90 ppb; 95% CI, 0.38-5.43 ppb; P=0.02). We did not detect
association between the remaining risk factors and neonatal FeNO levels.
CONCLUSION: Increased FeNO in healthy newborns seems strongly influenced by
genetics including father's atopy and child's variants in the DENND1B locus at
chromosome 1q31.3.
PMID- 24347561
TI - Dried bonito dashi: a preferred fish broth without postoral reward actions in
mice.
AB - The flavor of dashi, the broth prepared from dried bonito tuna, is attractive to
humans and rodents. The present experiments examined the ability of dashi to
serve as an oral and/or postoral rewarding stimulus for conditioned flavor
preferences in mice. In Experiment 1, C57BL/6J (B6) mice were infused
intragastrically with dashi when they consumed a conditioned stimulus (CS)+
flavor and with water when they drank a CS- flavor on alternate days. Postoral
dashi did not condition a CS+ preference. The combined effects of oral and
postoral dashi exposure were examined in Experiment 2, in which B6 mice consumed
a CS+ flavored dashi solution and CS- flavored water on alternate days. The mice
did not prefer the CS+ to CS- when both flavors were presented in water. Yet, the
B6 mice in both experiments preferred dashi to water in oral tests. Experiment 3
showed that taste-impaired Trpm5 knockout (KO) mice did not learn to prefer dashi
after exposure to it, in contrast to previous findings with the umami prototype
monosodium glutamate. This was not due to an inability to taste dashi, because
Trpm5 KO mice learned a strong preference for dashi after it was mixed with
glucose. The impact of dashi on reward may largely reflect an enhancement of
association of oral and postoral effects of food.
PMID- 24347562
TI - Lower extremity kinematics of a single-leg squat with an orthotic in male and
female collegiate athletes.
AB - Kinematic differences have been linked to the gender discrepancies seen in knee
injuries. A medially posted orthotic decreases frontal and transverse plane
motions in the lower extremity during ambulation, squatting and landing. This
study investigated the effect of a medial post on amount and timing of lower
extremity motions during a single-leg squat in male and female athletes. We
hypothesized there would be differences in these kinematic variables dependent
upon sex and post conditions. Twenty male and female athletes performed single
leg squats with and without a five degree full-length medial post. Maximum joint
angles were analyzed using a two-way, repeated-measures analysis of variance to
determine if the differences created by post condition were statistically
significant, whether there were gender differences, or interactions. Differences
in maximum motion values and the time at which they occurred were found between
men and women at the hip, knee and ankle. The post decreased all frontal plane
measures in both sexes and resulted in earlier attainment of maximum ankle
eversion and delayed maximum knee valgus. A medially posted orthotic may be
beneficial not only in limiting motion, but in affecting the time in which
stressful motions occur.
PMID- 24347563
TI - Socially induced placebo analgesia: a comparison of a pre-recorded versus live
face-to-face observation.
AB - BACKGROUND: Recently, it has been shown that live, face-to-face social
observation induces marked placebo analgesia. Despite the phenomenal growth of
video sharing platforms, the potential analgesic effects of video-based social
observation are largely unknown. This study compared video-based and live social
observation induced placebo analgesia and whether there was a similar
relationship between analgesic responses and empathy traits for both conditions.
METHODS: Here, we compared placebo analgesia in four groups: social observation
through a video (SOV group), social observation in person (SOP group), verbal
suggestion alone (VS group) and a natural history group (NH group). The SOV and
SOP groups underwent a placebo treatment and painful stimuli following
respectively a video-based and live observation of a demonstrator showing
analgesic effects when the painful stimuli were paired to a green light but not a
red light. The VS group received painful stimuli after they had been verbally
instructed to expect less pain after the green light. The NH group received
painful stimuli, but was told nothing about the meaning of the lights. Individual
pain reports and empathy traits were measured. RESULTS: We found that video-based
observation induced substantial placebo analgesic responses that were of similar
magnitude to live observation. Notably, the analgesic scores were strongly
correlated with empathetic concern in the live observation group but not in the
video replay group. CONCLUSIONS: These findings add evidence that placebo
analgesia can be induced by social observation and that empathy interacts with
these effects in a context-dependent manner.
PMID- 24347564
TI - A screen for bacterial endosymbionts in the model organisms Tribolium castaneum,
T. confusum, Callosobruchus maculatus, and related species.
AB - Reproductive parasites such as Wolbachia are extremely widespread amongst the
arthropods and can have a large influence over the reproduction and fitness of
their hosts. Undetected infections could thus confound the results of a wide
range of studies that focus on aspects of host behavior, reproduction, fitness,
and degrees of reproductive isolation. This potential problem has already been
underlined by work investigating the incidence of Wolbachia infections in stocks
of the model system Drosophila melanogaster. Here we survey a range of lab stocks
of further commonly used model arthropods, focusing especially on the flour
beetles Tribolium castaneum and Tribolium confusum, the cowpea weevil
Callosobruchus maculatus and related species (Coleoptera: Tenebrionidae and
Bruchidae). These species are widespread stored product pests so knowledge of
infections with symbionts further has potential use in informing biocontrol
measures. Beetles were assessed for infection with 3 known microbial reproductive
parasites: Wolbachia, Rickettsia, Spiroplasma. Infections with some of these
microbes were found in some of the lab stocks studied, although overall
infections were relatively rare. The consequences of finding infections in these
or other species and the type of previous studies likely to be affected most are
discussed.
PMID- 24347565
TI - Sensitivity of joint kinematics and kinetics to different pose estimation
algorithms and joint constraints in the elderly.
AB - The purpose of this research was to study the sensitivity of lower limb joint
kinematics and kinetics, calculated during different functional tasks (walking,
stair descent and stair ascent) in a sample of older adults, to different pose
estimation algorithms and models' joint constraints. Three models were developed
and optimized differently: in one model, each segment had 6 degrees of freedom
(segment optimization, SO), while in the other two, global optimization (GO) was
used, with different joint constraints: (1) GO, allowing all joint rotations; (2)
GOR, allowing three rotations at the hip, one at the knee (flexion/extension) and
two at the ankle (dorsi/plantar flexion and eversion/inversion). The results
showed that joint angles are more sensitive to the model's constraints than joint
moments and, the more restrictive the model, the higher the differences between
models, especially for the frontal and transverse planes (max. RMS difference
during gait: 11.7 degrees (64%) vs 0.12 N.m/kg (35.4%). In addition, except for
knee abduction/adduction angle, differences between SO and GO models were
relatively low. Since GO avoids the nonanatomical dislocations sometimes observed
in SO, choosing this model seems to be reasonable for future studies with a
similar sample and study design.
PMID- 24347566
TI - Influence of dorsiflexion shoes on jump performance.
AB - The goal of dorsiflexion sports shoes is to increase jumping capacity by means of
a lower position of the heel in relation to the forefoot which results in
additional stretching of the ankle plantar flexors. The aim of this study was to
compare a dorsiflexion sports shoe model with two conventional sports shoe models
in a countermovement jump test. The sample consisted of 35 participants who
performed a countermovement jump test on a force platform wearing the three
models of shoes. There were significant differences in the way force was
manifested (P<0.05) in the countermovement jump test, with a decrease in the
velocity of the center of gravity and an increase in force at peak power and mean
force in the concentric phase. Moreover, peak power was reached earlier with the
dorsiflexion sports shoe model. The drop of the center of gravity was increased
in CS1 in contrast to the dorsiflexion sports shoe model (P<.05). However, the
dorsiflexion sports shoes were not effective for improving either peak power or
jump height (P>.05). Although force manifestation and jump kinetics differ
between dorsiflexion shoes and conventional sports shoes, jump performance was
similar.
PMID- 24347567
TI - NAMPT (visfatin), a direct target of hypoxia-inducible factor-2alpha, is an
essential catabolic regulator of osteoarthritis.
AB - OBJECTIVE: Hypoxia-inducible factor 2alpha (HIF-2alpha), encoded by Epas1, causes
osteoarthritic cartilage destruction by regulating the expression of matrix
degrading enzymes. We undertook this study to explore the role of nicotinamide
phosphoribosyltransferase (NAMPT or visfatin) in HIF-2alpha-mediated
osteoarthritic cartilage destruction. METHODS: The expression of HIF-2alpha,
NAMPT and matrix-degrading enzymes was determined at the mRNA and protein levels
in human osteoarthritis (OA) cartilage, mouse experimental OA cartilage and
primary cultured mouse chondrocytes. Experimental OA in mice was induced by
destabilisation of the medial meniscus (DMM) surgery or intra-articular injection
of Ad-Epas1 or Ad-Nampt in wild-type, Epas1(+/-), Epas1(fl/fl);Col2a1-Cre and
Col2a1-Nampt transgenic (TG) mice. Primary cultured mouse chondrocytes were
treated with recombinant NAMPT protein or were infected with adenoviruses.
RESULTS: We found that the Nampt gene is a direct target of HIF-2alpha in
articular chondrocytes and OA cartilage. NAMPT protein, in turn, increased mRNA
levels and activities of MMP3, MMP12 and MMP13 in chondrocytes, an action that
was necessary for HIF-2alpha-induced expression of catabolic enzymes. Gain-of
function studies (intra-articular injection of Ad-Nampt; Col2a1-Nampt TG mice)
and loss-of-function studies (intra-articular injection of the NAMPT inhibitor
FK866) demonstrated that NAMPT is an essential catabolic regulator of
osteoarthritic cartilage destruction caused by HIF-2alpha or DMM surgery.
CONCLUSIONS: Our findings indicate that NAMPT, whose corresponding gene is a
direct target of HIF-2alpha, plays an essential catabolic role in OA pathogenesis
and acts as a crucial mediator of osteoarthritic cartilage destruction caused by
HIF-2alpha or DMM surgery.
PMID- 24347568
TI - Use of statins is associated with a lower prevalence of generalised
osteoarthritis.
PMID- 24347569
TI - Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the
BELISS open-label phase II study.
AB - BACKGROUND: Increased expression of B cell activating factor (BAFF or B
lymphocyte stimulator) may explain the B cell activation characteristic of
primary Sjogren's syndrome (pSS). OBJECTIVES: To evaluate the efficacy and safety
of belimumab, targeting BAFF, in patients with pSS. METHODS: Patients were
included in this bi-centric prospective 1-year open-label trial if they fulfilled
American European Consensus group criteria, were anti-Sjogren's syndrome A
positive and had current systemic complications or salivary gland enlargement, or
early disease (<5 years), or biomarkers of B cell activation. They received
belimumab, 10 mg/kg, at weeks 0, 2 and 4 and then every 4 weeks to week 24. The
primary end-point, assessed at week 28, was improvement in two of five items:
reduction in >=30% in dryness score on a visual analogue scale (VAS), >=30% in
fatigue VAS score, >=30% in VAS pain score, >=30% in systemic activity VAS
assessed by the physician and/or >25% improvement in any B cell activation
biomarker values. RESULTS: Among 30 patients included, the primary end-point was
achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR)
Sjogren's Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6)
(p=0.0015) and EULAR) Sjogren's Syndrome Patient Reported Index from 6.4 (1.1) to
5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8
(1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to
4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer's test did not
change. CONCLUSIONS: These encouraging results justify future randomised
controlled trials of belimumab in a selected target population of pSS patients
most likely to benefit from treatment.
PMID- 24347570
TI - Association between childhood overweight measures and adulthood knee pain,
stiffness and dysfunction: a 25-year cohort study.
AB - OBJECTIVE: To describe the associations between overweight measures in childhood
and knee pain, stiffness and dysfunction among adults 25 years later. METHODS:
Subjects broadly representative of the Australian population (n=449, aged 31-41
years, female 48%) were selected from the Australian Schools Health and Fitness
Survey of 1985. Height, weight and knee injury were recorded and knee pain was
assessed using the Western Ontario and McMaster Universities osteoarthritis index
(WOMAC). Childhood height, weight and knee injury had been measured according to
standard protocols 25 years earlier and body mass index (BMI) and percentage
overweight were calculated. RESULTS: The prevalence of knee pain was 34% and
overweight in childhood and adulthood was 7% and 48%, respectively. Overall,
there were no significant associations between childhood overweight measures and
total WOMAC knee pain, stiffness and dysfunction scores in adulthood. However, in
men, overweight in childhood was associated with adulthood WOMAC pain (relative
risk (RR) 1.72, 95% CI 1.11 to 2.69) and childhood weight and BMI were associated
with WOMAC stiffness and dysfunction. Childhood weight, BMI and overweight were
all associated with the presence of adulthood walking knee pain in men and the
whole sample. Most of these associations were independent of adult overweight
measures. Subjects who were overweight in both childhood and adult life had a
significant increase in the risk and prevalence of adulthood walking pain
(RR=2.42, 95% CI 1.06 to 5.53). CONCLUSIONS: Childhood overweight measures were
significantly associated with adulthood knee mechanical joint pain, stiffness and
dysfunction among men, independent of adult overweight, suggesting that childhood
overweight may lead to later knee symptoms in men.
PMID- 24347571
TI - Defining criteria for high disease activity in juvenile idiopathic arthritis
based on the juvenile arthritis disease activity score.
AB - OBJECTIVE: To determine cutoff values for defining the state of high disease
activity (HDA) in juvenile idiopathic arthritis (JIA) using the Juvenile
Arthritis Disease Activity Score (JADAS). METHODS: For the selection of cutoff
values, data from a clinical database including 609 patients were used. Optimal
cutoff values were determined against external criteria by calculating the 25th
and 10th centile of cumulative score distribution and through receiver operating
characteristic curve analysis. External criteria were based on the therapeutic
decision made by the attending doctor. Cross-validation was performed using five
patient samples that included 1421 patients. RESULTS: The optimal cutoff values
were those obtained through the 90% fixed sensitivity method. The selected JADAS
cutoff values were the following: 4.2 and 8.5 for JADAS27 in oligoarthritis and
polyarthritis, respectively; 4.2 and 10.5 for both JADAS10 and JADAS71 in
oligoarthritis and polyarthritis, respectively. In cross-validation analyses, the
cutoff values showed strong ability to discriminate between different levels of
American College of Rheumatology paediatric response in two clinical trials and
could predict worse functional and radiographic outcome. CONCLUSIONS: Cutoff
values for classifying HDA in JIA using the JADAS were developed. In cross
validation analyses, they proved to have good construct and discriminant validity
and ability to predict disease outcome.
PMID- 24347572
TI - Genetic variation in VTCN1 (B7-H4) is associated with course of disease in
juvenile idiopathic arthritis.
AB - OBJECTIVE: The course of disease in juvenile idiopathic arthritis (JIA) is
unpredictable with episodes of activity and remission. In order to identify
predictive factors, 93 SNPs, JIA subtype, age at onset and ANA status were
studied in relation to disease course. METHODS: Genetic and clinical parameters
were analysed in a cohort of 272 Caucasian patients with persistent
oligoarthritis (n=129), extended oligoarthritis (n=57) and rheumatoid factor
negative polyarthritis (n=86). Categories of disease course (remitting (n=65),
intermediate (n=96) and unremitting (n=111)) were designed based on the
cumulative time spent in active disease in the first 2 years. RESULTS: Univariate
analysis revealed association of the course of disease with JIA subtype
(p=5.7*10(-5)) and three SNPs; VTCN1 rs10 923 223 (p=4.4*10(-5)), VTCN1 rs12 046
117 (p=0.017) and CDK6 rs42 041 (p=0.038). In a subsequent multivariate ordinal
logistic regression analysis, VTCN1 rs10 923 223 (OR 0.41, 95%-CI 0.26 to 0.63)
and JIA subtype (OR 3.8, 95%-CI 2.0 to 7.2; OR 2.5, 95%-CI 1.4 to 4.2, for
extended oligoarthritis and RF-negative polyarthritis vs persistent
oligoarthritis, respectively) were the strongest independent factors for course
of disease. CONCLUSIONS: This study provides evidence that VTCN1, encoding B7-H4,
is associated with course of disease in selected subtypes of JIA. VTCN1 might be
useful in predicting the course of disease.
PMID- 24347573
TI - Children's sleep patterns from 0 to 9 years: Australian population longitudinal
study.
AB - OBJECTIVE: To provide accurate population normative data documenting cross
sectional, age-specific sleep patterns in Australian children aged 0-9 years.
DESIGN AND SETTING: The first three waves of the nationally representative
Longitudinal Study of Australian Children, comprising two cohorts recruited in
2004 at ages 0-1 years (n=5107) and 4-5 years (n=4983), and assessed biennially.
PARTICIPANTS: Children with analysable sleep data for at least one wave.
MEASURES: At every wave, parents prospectively completed 24-h time-use diaries
for a randomly selected week or weekend day. 'Sleeping, napping' was one of the
26 precoded activities recorded in 15-min time intervals. RESULTS: From 0 to 9
years of age, 24-h sleep duration fell from a mean peak of 14 (SD 2.2) h at 4-6
months to 10 (SD 1.9) h at 9 years, mainly due to progressively later mean sleep
onset time from 20:00 (SD 75 min) to 21:00 (SD 60 min) and declining length of
day sleep from 3.0 (SD 1.7) h to 0.03 (SD 0.2) h. Number and duration of night
wakings also fell. By primary school, wake and sleep onset times were markedly
later on weekend days. The most striking feature of the centile charts is the
huge variation at all ages in sleep duration, sleep onset time and, especially,
wake time in this normal population. CONCLUSIONS: Parents and professionals can
use these new centile charts to judge normalcy of children's sleep. In future
research, these population parameters will now be used to empirically determine
optimal child sleep patterns for child and parent outcomes like mental and
physical health.
PMID- 24347575
TI - The evolution of neurorehabilitation and neural repair.
PMID- 24347574
TI - Childhood vaccination coverage by ethnicity within London between 2006/2007 and
2010/2011.
AB - OBJECTIVES: To assess childhood vaccination coverage at first, second and fifth
birthdays by ethnicity in London between 2006/2007 and 2010/2011 and identify
factors relating to lower coverage. DESIGN: Data concerning receipt of diphtheria
containing vaccines were extracted from child health information systems (CHISs)
and sent to the Health Protection Agency. SETTING: Nine London Primary Care
Trusts (PCTs). PARTICIPANTS: Records for 315 381 children born April 2001-March
2010. MAIN OUTCOME MEASURES: Receipt of a full primary course of diphtheria
containing vaccines at first and second birthdays, and a primary course and
preschool booster at fifth birthday. RESULTS: Consistently good vaccine coverage
of the primary course (>88% at first birthday, >89% at second birthday) was
achieved across the five largest ethnic groups. Coverage of the preschool booster
at fifth birthday was >65% across the five largest ethnic groups. Lowest coverage
was observed in smaller ethnic groups. Deprivation was not a strong indicator of
coverage overall, and for most ethnic groups there was no relationship between
deprivation and coverage. Coverage was significantly lower in children not
assigned to a general practitioner practice in the CHIS. CONCLUSIONS: Smaller,
less well-established ethnic groups within a PCT may require specific targeting
to ensure children are fully immunised and to improve record keeping.
Unregistered children need particular attention and may be missed by current
scheduling processes in London. In order to monitor the impact of the current
National Health Service (NHS) reorganisation on inequalities in access to
healthcare data on country of birth, in addition to ethnicity, should be
available for analysis.
PMID- 24347576
TI - Compressive biological sequence analysis and archival in the era of high
throughput sequencing technologies.
AB - High-throughput sequencing technologies produce large collections of data, mainly
DNA sequences with additional information, requiring the design of efficient and
effective methodologies for both their compression and storage. In this context,
we first provide a classification of the main techniques that have been proposed,
according to three specific research directions that have emerged from the
literature and, for each, we provide an overview of the current techniques.
Finally, to make this review useful to researchers and technicians applying the
existing software and tools, we include a synopsis of the main characteristics of
the described approaches, including details on their implementation and
availability. Performance of the various methods is also highlighted, although
the state of the art does not lend itself to a consistent and coherent comparison
among all the methods presented here.
PMID- 24347578
TI - Interventions designed to reduce sedentary behaviours in young people: a review
of reviews.
AB - BACKGROUND: Leisure time is increasingly spent in sedentary pursuits such as
screen-viewing (eg, television/DVD viewing and computer use), motorised travel,
school/work and sitting-based socialising (eg, social media and chatting).
Sedentary screen time, particularly TV, appears to play an important role in the
aetiology of obesity due to its co-occurrence with other unhealthy behaviours
such as snacking on energy-dense foods, low levels of physical activity and
inadequate sleep. More information is needed on how to reduce sedentary
behaviours. Most interventions have focused on young people and a number of
systematic reviews exist on this topic. OBJECTIVE: To synthesise systematic
reviews and meta-analyses of interventions aimed at decreasing sedentary
behaviours among children and adolescents. METHODS: Papers were located from
computerised and manual searches. Included articles were English language
systematic reviews or meta-analyses of interventions aiming at reducing sedentary
behaviour in children (<11 years) and adolescents (12-18 years). RESULTS: Ten
papers met the inclusion criteria and were analysed. All reviews concluded some
level of effectiveness in reducing time spent in sedentary behaviour. When an
effect size was reported, there was a small but significant reduction in
sedentary time (highest effect size=-0.29; CI -0.35 to -0.22). Moderator analyses
showed a trend favouring interventions with children younger than 6 years.
Effective strategies include the involvement of family, behavioural interventions
and electronic TV monitoring devices. CONCLUSIONS: Results from systematic
reviews and meta-analyses show that interventions to reduce children's sedentary
behaviour have a small but significant effect. Future research should expand
these findings examining interventions targeting different types of sedentary
behaviours and the effectiveness of specific behaviour change techniques across
different contexts and settings.
PMID- 24347577
TI - Fetal striatal grafting slows motor and cognitive decline of Huntington's
disease.
AB - OBJECTIVE: To assess the clinical effect of caudate-putaminal transplantation of
fetal striatal tissue in Huntington's disease (HD). METHODS: We carried out a
follow-up study on 10 HD transplanted patients and 16 HD not-transplanted
patients. All patients were evaluated with the Unified HD Rating Scale (UHDRS)
whose change in motor, cognitive, behavioural and functional capacity total
scores were considered as outcome measures. Grafted patients also received
morphological and molecular neuroimaging. RESULTS: Patients were followed-up from
disease onset for a total of 309.3 person-years (minimum 5.3, median 11.2 years,
maximum 21.6 years). UHDRS scores have been available since 2004 (median time of
5.7 years since onset, minimum zero, maximum 17.2 years). Median post
transplantation follow-up was 4.3 years, minimum 2.8, maximum 5.1 years. Adjusted
post-transplantation motor score deterioration rate was reduced compared to the
pretransplantation period, and to that of not-transplanted patients by 0.9
unit/years (95% CI 0.2 to 1.6). Cognitive score deterioration was reduced of 2.7
unit/years (95% CI 0.1 to 5.3). For grafted patients the 2-year post
transplantation [(18)F]fluorodeoxyglucose positron emission tomography (PET)
showed striatal/cortical metabolic increase compared to the presurgical
evaluation; 4-year post-transplantation PET values were slightly decreased, but
remained higher than preoperatively. [(123)I]iodobenzamide single photon emission
CT demonstrated an increase in striatal D2-receptor density during postgrafting
follow-up. CONCLUSIONS: Grafted patients experienced a milder clinical course
with less pronounced motor/cognitive decline and associated brain metabolism
improvement. Life-time follow-up may ultimately clarify whether transplantation
permanently modifies the natural course of the disease, allowing longer sojourn
time at less severe clinical stage, and improvement of overall survival.
PMID- 24347580
TI - Dr Anne Szarewski: 1 September 1959-24 August 2013.
PMID- 24347581
TI - The barrier to abortion is politics.
PMID- 24347583
TI - "I honestly didn't know that I could": the rise and rise of in-pharmacy sexual
and reproductive health guidance.
PMID- 24347584
TI - The birth of mankind.
PMID- 24347585
TI - Reproductive Health Matters.
PMID- 24347586
TI - Comment on 'vasectomy: replacing the preoperative outpatient appointment with a
DVD'.
PMID- 24347587
TI - Comment on 'vasectomy: replacing the preoperative outpatient appointment with a
DVD': authors' response.
PMID- 24347588
TI - Comment on 'embracing post-fertilisation methods of family planning: a call to
action'.
PMID- 24347589
TI - Comment on 'Embracing post-fertilisation methods of family planning: a call to
action': authors' response.
PMID- 24347590
TI - Not all IUDs fit in young nulliparous and adolescent women.
PMID- 24347591
TI - HPV knowledge and vaccine acceptability in Appalachian Tennessee and Kentucky,
USA.
PMID- 24347592
TI - Comment on 'infections post-Nexplanon(R) insertion'.
PMID- 24347594
TI - A systematic review of symptomatic diagnosis of lung cancer.
AB - BACKGROUND: Lung cancer (LC) is often diagnosed late when curative intervention
is no longer viable. However, current referral guidelines (e.g. UK National
Institute for Health and Care Excellence guidelines) for suspected LC are based
on a weak evidence base. Aim. The purpose of this systematic review is to
identify symptoms that are independently associated with LC and to identify the
key methodological issues relating to symptomatic diagnosis research in LC.
METHODS: Medline, Ovid and Cumulative Index to Nursing and Allied Health
Literature were searched for the period between 1946 and 2012 using the MeSH
terms 'lung cancer' and 'symptom*'. Quality of each paper was assessed using
Scottish Intercollegiate Guidelines Network and Consolidated Criteria for
Reporting Qualitative Research Checklists and checked by a second and third
reviewer. RESULTS: Evidence regarding the diagnostic values of most symptoms was
inconclusive; haemoptysis was the only symptom consistently indicated as a
predictor of LC. Generally, evidence was weakened by methodological issues such
as the lack of standardized data collection (recording bias) and the lack of
comparability of findings across the different studies that extend beyond the
spectrum of disease. Qualitative studies indicated that patients with LC
experienced symptoms months before diagnosis but did not interpret them as
serious enough to seek health care. Therefore, early LC symptoms might be under
represented in primary care clinical notes. CONCLUSION: Current evidence is
insufficient to suggest a symptom profile for LC across the disease stages, nor
can it be concluded that classical LC symptoms are predictors of LC apart from,
perhaps, haemoptysis. Prospective studies are now needed that systematically
record symptoms and explore their predictive values for LC diagnosis.
PMID- 24347595
TI - Atrial tachycardia after ablation of persistent atrial fibrillation: is it us or
them?
PMID- 24347596
TI - Unipolar electrogram morphology to assess lesion formation during catheter
ablation of atrial fibrillation: successful translation into clinical practice.
PMID- 24347597
TI - Deliberate epicardial catheter ablation lesions: making outside contact.
PMID- 24347598
TI - Wave-mapping as a guide for ablation of atrial fibrillation: a daydream?
PMID- 24347599
TI - Who should receive the subcutaneous implanted defibrillator?: The subcutaneous
implantable cardioverter defibrillator (ICD) should be considered in all ICD
patients who do not require pacing.
PMID- 24347600
TI - Who should receive the subcutaneous implanted defibrillator?: Timing is not right
to replace the transvenous implantable cardioverter defibrillator.
PMID- 24347601
TI - Letter by Morris et al regarding article, "Low heart rates predict incident
atrial fibrillation in healthy middle-aged men" by Grundvold et al.
PMID- 24347602
TI - Response to Letter by Morris et al regarding article, "Low heart rates predict
incident atrial fibrillation in healthy middle-aged men" by Grundvold et al.
PMID- 24347603
TI - New diagnostic and therapeutic approaches to treat ventricular tachycardias
originating at the summit of the left ventricle: role of merged hemodynamic-MRI
and alternative ablation sources.
PMID- 24347604
TI - Similia similibus curantur.
PMID- 24347605
TI - Bundle branch reentrant ventricular tachycardia with wide and narrow QRS
morphology.
PMID- 24347606
TI - Bundles branch reentry.
PMID- 24347607
TI - Fundamental concepts in electrophysiology in cases and reviews.
PMID- 24347608
TI - Carbon ion radiotherapy of human lung cancer attenuates HIF-1 signaling and acts
with considerably enhanced therapeutic efficiency.
AB - Carbon ion irradiation is an emerging therapeutic option for various tumor
entities. Radiation resistance of solid tumors toward photon irradiation is
caused by attenuation of DNA damage in less oxygenated tumor areas and by
increased hypoxia-inducible factor (HIF)-1 signaling. Carbon ion irradiation acts
independently of oxygen; however, the role of HIF-1 is unclear. We analyzed the
effect of HIF-1 signaling after carbon ions in comparison to photons by using
biological equivalent radiation doses in a human non-small-cell cancer model. The
studies were performed in cultured A549 and H1299 cell lines and in A549
xenografts. Knockdown of HIF-1alpha in vivo combined with photon irradiation
delayed tumor growth (23 vs. 13 d; P<0.05). Photon irradiation induced HIF-1alpha
and target genes, predominantly in oxygenated cells (1.6-fold; P<0.05), with
subsequent enhanced tumor angiogenesis (1.7-fold; P<0.05). These effects were not
observed after carbon ion irradiation. Micro-DNA array analysis indicated that
photons, but not carbon ions, significantly induced components of the mTOR
(mammalian target of rapamycin) pathway (gene set enrichment analysis; P<0.01) as
relevant for HIF-1alpha induction. After carbon ion irradiation in vivo, we
observed substantially decreased HIF-1alpha levels (8.9-fold; P<0.01) and
drastically delayed tumor growth (P<0.01), an important finding that indicates a
higher relative biological effectiveness (RBE) than anticipated from the cell
survival data. Taken together, the evidence showed that carbon ions mediate an
improved therapeutic effectiveness without tumor-promoting HIF-1 signaling.
PMID- 24347609
TI - Mechanosensing through focal adhesion-anchored intermediate filaments.
AB - Integrin-based mechanotransduction involves a complex focal adhesion (FA)
associated machinery that is able to detect and respond to forces exerted either
through components of the extracellular matrix or the intracellular contractile
actomyosin network. Here, we show a hitherto unrecognized regulatory role of
vimentin intermediate filaments (IFs) in this process. By studying fibroblasts in
which vimentin IFs were decoupled from FAs, either because of vimentin deficiency
(V0) or loss of vimentin network anchorage due to deficiency in the cytolinker
protein plectin (P0), we demonstrate attenuated activation of the major
mechanosensor molecule FAK and its downstream targets Src, ERK1/2, and p38, as
well as an up-regulation of the compensatory feedback loop acting on RhoA and
myosin light chain. In line with these findings, we show strongly reduced FA
turnover rates in P0 fibroblasts combined with impaired directional migration,
formation of protrusions, and up-regulation of "stretched" high-affinity integrin
complexes. By exploiting tension-independent conditions, we were able to
mechanistically link these defects to diminished cytoskeletal tension in both P0
and V0 cells. Our data provide important new insights into molecular mechanisms
underlying cytoskeleton-regulated mechanosensing, a feature that is fundamental
for controlled cell movement and tumor progression.
PMID- 24347610
TI - In situ intracellular calcium oscillations in osteocytes in intact mouse long
bones under dynamic mechanical loading.
AB - Osteocytes have been hypothesized to be the major mechanosensors in bone. How in
situ osteocytes respond to mechanical stimuli is still unclear because of
technical difficulties. In vitro studies have shown that osteocytes exhibited
unique calcium (Ca(2+)) oscillations to fluid shear. However, whether this
mechanotransduction phenomenon holds for in situ osteocytes embedded within a
mineralized bone matrix under dynamic loading remains unknown. Using a novel
synchronized loading/imaging technique, we successfully visualized in real time
and quantified Ca(2+) responses in osteocytes and bone surface cells in situ
under controlled dynamic loading on intact mouse tibia. The resultant fluid
induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was
also quantified. Osteocytes, but not surface cells, displayed repetitive Ca(2+)
spikes in response to dynamic loading, with spike frequency and magnitude
dependent on load magnitude, tissue strain, and shear stress in the LCS. The
Ca(2+) oscillations were significantly reduced by endoplasmic reticulum (ER)
depletion and P2 purinergic receptor (P2R)/phospholipase C (PLC) inhibition. This
study provides direct evidence that osteocytes respond to in situ mechanical
loading by Ca(2+) oscillations, which are dependent on the P2R/PLC/inositol
trisphosphate/ER pathway. This study develops a novel approach in skeletal
mechanobiology and also advances our fundamental knowledge of bone
mechanotransduction.
PMID- 24347611
TI - Dystrophin insufficiency causes selective muscle histopathology and loss of
dystrophin-glycoprotein complex assembly in pig skeletal muscle.
AB - The purpose of this investigation was to determine the extent to which dystrophin
insufficiency caused histomorphological changes in a novel pig model of Becker
muscular dystrophy. In our procedures, we used a combination of biochemical
approaches, including quantitative PCR and Western blots, along with a
histological analysis using standard and immunohistological measures. We found
that 8-wk-old male affected pigs had a 70% reduction in dystrophin protein
abundance in the diaphragm, psoas major, and longissimus lumborum and a 5-fold
increase in serum creatine kinase activity compared with healthy male
littermates. Dystrophin insufficiency in the diaphragm and the longissimus
resulted in muscle histopathology with disorganized fibrosis that often
colocalized with fatty infiltration but not the psoas. Affected animals also had
an 80-85% reduction in alpha-sarcoglycan localization in these muscles,
indicating compromised assembly of the dystrophin glycoprotein complex. Controls
used in this study were 4 healthy male littermates, as they are most closely
related to the affected animals. We concluded that pigs with insufficient
dystrophin protein expression have a phenotype consistent with human
dystrophinopathy patients. Given that and their similarity in body size and
physiology to humans, we further conclude that this pig line is an appropriate
translational model for dystrophinopathies.
PMID- 24347612
TI - A-to-I RNA editing occurs at over a hundred million genomic sites, located in a
majority of human genes.
AB - RNA molecules transmit the information encoded in the genome and generally
reflect its content. Adenosine-to-inosine (A-to-I) RNA editing by ADAR proteins
converts a genomically encoded adenosine into inosine. It is known that most RNA
editing in human takes place in the primate-specific Alu sequences, but the
extent of this phenomenon and its effect on transcriptome diversity are not yet
clear. Here, we analyzed large-scale RNA-seq data and detected ~1.6 million
editing sites. As detection sensitivity increases with sequencing coverage, we
performed ultradeep sequencing of selected Alu sequences and showed that the
scope of editing is much larger than anticipated. We found that virtually all
adenosines within Alu repeats that form double-stranded RNA undergo A-to-I
editing, although most sites exhibit editing at only low levels (<1%). Moreover,
using high coverage sequencing, we observed editing of transcripts resulting from
residual antisense expression, doubling the number of edited sites in the human
genome. Based on bioinformatic analyses and deep targeted sequencing, we estimate
that there are over 100 million human Alu RNA editing sites, located in the
majority of human genes. These findings set the stage for exploring how this
primate-specific massive diversification of the transcriptome is utilized.
PMID- 24347614
TI - Exercise training reverses unparallel downregulation of MaxiK channel alpha- and
beta1-subunit to enhance vascular function in aging mesenteric arteries.
AB - This study was designed to determine the effects of aerobic exercise training on
aging-associated selective changes of the function and expression of the large
conductance Ca(2+)-activated K(+) (MaxiK) channels in mesenteric arteries. Male
Wistar rats aged 19-21 months were randomly assigned to sedentary (O-SED) and
exercise-trained groups (O-EX). Two-month-old rats were used as Young control.
Addition of iberiotoxin (10(-8) M) increased the norepinephrine-induced arterial
contraction in all three groups, with the greatest enhancement being in Young and
the least in O-SED. Patch clamp study revealed the characteristics of aging on
MaxiK channel function in mesenteric arteries, mainly including (a) decrease of
iberiotoxin-sensitive whole-cell K(+) current, (b) decrease of open probability
and Ca(2+)/voltage sensitivity of single MaxiK channel, and (c) reduction of
tamoxifen-induced MaxiK activation. After exercise training, all of these changes
were markedly inhibited. Western blotting revealed that the protein expression of
MaxiK was significantly reduced with aging and the suppression of beta1-subunit
was larger than that of alpha-subunit, although exercise training diminished this
alteration. Taken together, aerobic exercise training reverses the aging-related
unparallel downregulation of MaxiK alpha- and beta1-subunit expression on
mesenteric arteries, which partly underlies the beneficial effect of exercise on
restoring aging-associated reduction in mesenteric artery vasodilatory
properties.
PMID- 24347616
TI - Arrhythmogenic right ventricular cardiomyopathy: growing evidence for complex
inheritance.
PMID- 24347613
TI - A heart that beats for 500 years: age-related changes in cardiac proteasome
activity, oxidative protein damage and expression of heat shock proteins,
inflammatory factors, and mitochondrial complexes in Arctica islandica, the
longest-living noncolonial animal.
AB - Study of negligibly senescent animals may provide clues that lead to better
understanding of the cardiac aging process. To elucidate mechanisms of successful
cardiac aging, we investigated age-related changes in proteasome activity,
oxidative protein damage and expression of heat shock proteins, inflammatory
factors, and mitochondrial complexes in the heart of the ocean quahog Arctica
islandica, the longest-lived noncolonial animal (maximum life span potential: 508
years). We found that in the heart of A. islandica the level of oxidatively
damaged proteins did not change significantly up to 120 years of age. No
significant aging-induced changes were observed in caspase-like and trypsin-like
proteasome activity. Chymotrypsin-like proteasome activity showed a significant
early-life decline, then it remained stable for up to 182 years. No significant
relationship was observed between the extent of protein ubiquitination and age.
In the heart of A. islandica, an early-life decline in expression of HSP90 and
five mitochondrial electron transport chain complexes was observed. We found
significant age-related increases in the expression of three cytokine-like
mediators (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) in
the heart of A. islandica. Collectively, in extremely long-lived molluscs,
maintenance of protein homeostasis likely contributes to the preservation of
cardiac function. Our data also support the concept that low-grade chronic
inflammation in the cardiovascular system is a universal feature of the aging
process, which is also manifest in invertebrates.
PMID- 24347617
TI - Expanding the genetic spectrum of hypertrophic cardiomyopathy: X marks the spot.
PMID- 24347618
TI - Genome-wide linkage approach yields novel early onset myocardial infarction locus
in East Asians.
PMID- 24347619
TI - Translation of genetics research to clinical medicine: the National Heart, Lung,
and Blood Institute perspective.
PMID- 24347620
TI - A repair tool-(c)kit for the injured heart.
PMID- 24347621
TI - Salt, immune function, and the risk of autoimmune diseases.
PMID- 24347623
TI - Homogeneous nuclear background for mitochondrial cline in northern range of
Notochthamalus scabrosus.
AB - A mitochondrial cline along the Chilean coast in the barnacle Notochthamalus
scabrosus suggests a species history of transient allopatry and secondary
contact. However, previous studies of nuclear sequence divergence suggested
population genetic homogeneity across northern and central Chile. Here, we
collect single-nucleotide polymorphism data from pooled population samples
sequenced with restriction site-associated DNA sequencing procedures, confirm
these data with the use of a GoldenGate array, and identify a discordance between
population genetic patterns in the nuclear and mitochondrial genomes. This
discordance was noted in previous work on this species, but here it is confirmed
that the nuclear genome exhibits only slight phylogeographic variation across
3000 km of coastline, in the presence of a strong and statistically significant
mitochondrial cline. There are nevertheless markers (approximately 5% of nuclear
single-nucleotide polymorphisms) exhibiting cytonuclear disequilibrium relative
to mitotype. Although these data confirm our previous explorations of this
species, it is likely that some of the nuclear genomic diversity of this species
has yet to be explored, as comparison with other barnacle phylogeography studies
suggest that a divergence of similar magnitude should be found in the nuclear
genome somewhere else in the species range.
PMID- 24347622
TI - Identification of suppressors of mbk-2/DYRK by whole-genome sequencing.
AB - Screening for suppressor mutations is a powerful method to isolate genes that
function in a common pathway or process. Because suppressor mutations often do
not have phenotypes on their own, cloning of suppressor loci can be challenging.
A method combining whole-genome sequencing (WGS) and single nucleotide
polymorphism (SNP) mapping (WGS/SNP mapping) was developed to identify mutations
with visible phenotypes in C. elegans. We show here that WGS/SNP mapping is an
efficient method to map suppressor mutations without the need for previous
phenotypic characterization. Using RNA-mediated interference to test candidate
loci identified by WGS/SNP mapping, we identified 10 extragenic and six
intragenic suppressors of mbk-2, a DYRK family kinase required for the transition
from oocyte to zygote. Remarkably, seven suppressors are mutations in cell-cycle
regulators that extend the timing of the oocyte-to-zygote transition.
PMID- 24347624
TI - Genetic architecture of contemporary adaptation to biotic invasions: quantitative
trait locus mapping of beak reduction in soapberry bugs.
AB - Biological invasions can result in new selection pressures driven by the
establishment of new biotic interactions. The response of exotic and native
species to selection depends critically on the genetic architecture of
ecologically relevant traits. In the Florida peninsula, the soapberry bug (Jadera
haematoloma) has colonized the recently introduced Chinese flametree,
Koelreuteria elegans, as a host plant. Driven by feeding efficiency, the
populations associated with this new host have differentiated into a new bug
ecomorph characterized by short beaks more appropriate for feeding on the
flattened pods of the Chinese flametree. In this study, we have generated a three
generation pedigree from crossing the long-beaked and short-beaked ecomorphs to
construct a de novo linkage map and to locate putative quantitative trait locus
(QTL) controlling beak length and body size in J. haematoloma. Using amplified
fragment-length polymorphism markers and a two-way pseudo-testcross design, we
have produced two parental maps in six linkage groups, covering the known number
of chromosomes. QTL analysis revealed one significant QTL for beak length on a
maternal linkage group and the corresponding paternal linkage group. Three QTL
were found for body size. Through single marker regression analysis, nine single
markers that could not be placed on the map were also found to be significantly
associated with one or both of the two traits. Interestingly, the most
significant body size QTL co-localized with the beak length QTL, suggesting
linkage disequilibrium or pleiotropic effects of related traits. Our results
suggest an oligogenic control of beak length.
PMID- 24347625
TI - Genomic characterization of the mouse ribosomal DNA locus.
AB - The transcription of rRNA is critical to all living cells and is tightly
controlled at the level of chromatin structure. Although the widespread adoption
of genomic technologies including chromatin immunoprecipitation with massively
parallel short-read sequencing (ChIP-seq) has allowed for the interrogation of
chromatin structure on a genome-wide scale, until recently rDNA has not been
analyzed by this technique. We extended genomic analysis of rDNA to mouse (Mus
musculus), in which rDNA is similar in structure but highly divergent in sequence
compared with human rDNA. Comparison of rDNA histone marks between mouse
embryonic stem cells (mESCs) and more differentiated mouse cell types revealed
differences between pluripotent and differentiated states. We also observed
substantial divergence in rDNA histone modification patterns between mESCs and
human embryonic stem cells (hESCs). Surprisingly, we found that the pluripotency
factor OCT4 was bound to rDNA in similar patterns in mESCs and hESCs. Extending
this analysis, we found that an additional 17 pluripotency-associated factors
were bound to rDNA in mESCs, suggesting novel modes of rDNA regulation in
pluripotent cells. Taken together, our results provide a detailed view of rDNA
chromatin structure in an important model system and enable high-resolution
comparison of rDNA regulation between mouse and human.
PMID- 24347626
TI - Extensive use of RNA-binding proteins in Drosophila sensory neuron dendrite
morphogenesis.
AB - The large number of RNA-binding proteins and translation factors encoded in the
Drosophila and other metazoan genomes predicts widespread use of post
transcriptional regulation in cellular and developmental processes. Previous
studies identified roles for several RNA-binding proteins in dendrite branching
morphogenesis of Drosophila larval sensory neurons. To determine the larger
contribution of post-transcriptional gene regulation to neuronal morphogenesis,
we conducted an RNA interference screen to identify additional Drosophila
proteins annotated as either RNA-binding proteins or translation factors that
function in producing the complex dendritic trees of larval class IV dendritic
arborization neurons. We identified 88 genes encoding such proteins whose
knockdown resulted in aberrant dendritic morphology, including alterations in
dendritic branch number, branch length, field size, and patterning of the
dendritic tree. In particular, splicing and translation initiation factors were
associated with distinct and characteristic phenotypes, suggesting that different
morphogenetic events are best controlled at specific steps in post
transcriptional messenger RNA metabolism. Many of the factors identified in the
screen have been implicated in controlling the subcellular distributions and
translation of maternal messenger RNAs; thus, common post-transcriptional
regulatory strategies may be used in neurogenesis and in the generation of
asymmetry in the female germline and embryo.
PMID- 24347627
TI - Heterosis is prevalent among domesticated but not wild strains of Saccharomyces
cerevisiae.
AB - Crosses between inbred but unrelated individuals often result in an increased
fitness of the progeny. This phenomenon is known as heterosis and has been
reported for wild and domesticated populations of plants and animals. Analysis of
heterosis is often hindered by the fact that the genetic relatedness between
analyzed organisms is only approximately known. We studied a collection of
Saccharomyces cerevisiae isolates from wild and human-created habitats whose
genomes were sequenced and thus their relatedness was fully known. We reasoned
that if these strains accumulated different deleterious mutations at an
approximately constant rate, then heterosis should be most visible in F1
heterozygotes from the least related parents. We found that heterosis was
substantial and positively correlated with sequence divergence, but only in
domesticated strains. More than 80% of the heterozygous hybrids were more fit
than expected from the mean of their homozygous parents, and approximately three
quarters of those exceeded even the fittest parent. Our results support the
notion that domestication brings about relaxation of selection and accumulation
of deleterious mutations. However, other factors may have contributed as well. In
particular, the observed build-up of genetic load might be facilitated by a
decrease, and not increase, in the rate of inbreeding.
PMID- 24347628
TI - Multigenic natural variation underlies Caenorhabditis elegans olfactory
preference for the bacterial pathogen Serratia marcescens.
AB - The nematode Caenorhabditis elegans can use olfaction to discriminate among
different kinds of bacteria, its major food source. We asked how natural genetic
variation contributes to choice behavior, focusing on differences in olfactory
preference behavior between two wild-type C. elegans strains. The laboratory
strain N2 strongly prefers the odor of Serratia marcescens, a soil bacterium that
is pathogenic to C. elegans, to the odor of Escherichia coli, a commonly used
laboratory food source. The divergent Hawaiian strain CB4856 has a weaker
attraction to Serratia than the N2 strain, and this behavioral difference has a
complex genetic basis. At least three quantitative trait loci (QTLs) from the
CB4856 Hawaii strain (HW) with large effect sizes lead to reduced Serratia
preference when introgressed into an N2 genetic background. These loci interact
and have epistatic interactions with at least two antagonistic QTLs from HW that
increase Serratia preference. The complex genetic architecture of this C. elegans
trait is reminiscent of the architecture of mammalian metabolic and behavioral
traits.
PMID- 24347629
TI - Genome-wide association study of periodontal health measured by probing depth in
adults ages 18-49 years.
AB - The etiology of chronic periodontitis clearly includes a heritable component. Our
purpose was to perform a small exploratory genome-wide association study in
adults ages 18-49 years to nominate genes associated with periodontal disease
related phenotypes for future consideration. Full-mouth periodontal pocket depth
probing was performed on participants (N = 673), with affected status defined as
two or more sextants with probing depths of 5.5 mm or greater. Two variations of
this phenotype that differed in how missing teeth were treated were used in
analysis. More than 1.2 million genetic markers across the genome were genotyped
or imputed and tested for genetic association. We identified ten suggestive loci
(p-value <= 1E-5), including genes/loci that have been previously implicated in
chronic periodontitis: LAMA2, HAS2, CDH2, ESR1, and the genomic region on
chromosome 14q21-22 between SOS2 and NIN. Moreover, we nominated novel loci not
previously implicated in chronic periodontitis or related pathways, including the
regions 3p22 near OSBPL10 (a lipid receptor implicated in hyperlipidemia), 4p15
near HSP90AB2P (a heat shock pseudogene), 11p15 near GVINP1 (a GTPase
pseudogene), 14q31 near SEL1L (an intracellular transporter), and 18q12 in FHOD3
(an actin cytoskeleton regulator). Replication of these results in additional
samples is needed. This is one of the first research efforts to identify genetic
polymorphisms associated with chronic periodontitis-related phenotypes by the
genome-wide association study approach. Though small, efforts such this are
needed in order to nominate novel genes and generate new hypotheses for
exploration and testing in future studies.
PMID- 24347631
TI - Horizontal gene transfer can rescue prokaryotes from Muller's ratchet: benefit of
DNA from dead cells and population subdivision.
AB - Horizontal gene transfer (HGT) is a major factor in the evolution of prokaryotes.
An intriguing question is whether HGT is maintained during evolution of
prokaryotes owing to its adaptive value or is a byproduct of selection driven by
other factors such as consumption of extracellular DNA (eDNA) as a nutrient. One
hypothesis posits that HGT can restore genes inactivated by mutations and thereby
prevent stochastic, irreversible deterioration of genomes in finite populations
known as Muller's ratchet. To examine this hypothesis, we developed a population
genetic model of prokaryotes undergoing HGT via homologous recombination.
Analysis of this model indicates that HGT can prevent the operation of Muller's
ratchet even when the source of transferred genes is eDNA that comes from dead
cells and on average carries more deleterious mutations than the DNA of recipient
live cells. Moreover, if HGT is sufficiently frequent and eDNA diffusion
sufficiently rapid, a subdivided population is shown to be more resistant to
Muller's ratchet than an undivided population of an equal overall size. Thus, to
maintain genomic information in the face of Muller's ratchet, it is more
advantageous to partition individuals into multiple subpopulations and let them
"cross-reference" each other's genetic information through HGT than to collect
all individuals in one population and thereby maximize the efficacy of natural
selection. Taken together, the results suggest that HGT could be an important
condition for the long-term maintenance of genomic information in prokaryotes
through the prevention of Muller's ratchet.
PMID- 24347630
TI - Global analysis of serine/threonine and tyrosine protein phosphatase catalytic
subunit genes in Neurospora crassa reveals interplay between phosphatases and the
p38 mitogen-activated protein kinase.
AB - Protein phosphatases are integral components of the cellular signaling machinery
in eukaryotes, regulating diverse aspects of growth and development. The genome
of the filamentous fungus and model organism Neurospora crassa encodes catalytic
subunits for 30 protein phosphatase genes. In this study, we have characterized
24 viable N. crassa phosphatase catalytic subunit knockout mutants for phenotypes
during growth, asexual development, and sexual development. We found that 91% of
the mutants had defects in at least one of these traits, whereas 29% possessed
phenotypes in all three. Chemical sensitivity screens were conducted to reveal
additional phenotypes for the mutants. This resulted in the identification of at
least one chemical sensitivity phenotype for 17 phosphatase knockout mutants,
including novel chemical sensitivities for two phosphatase mutants lacking a
growth or developmental phenotype. Hence, chemical sensitivity or
growth/developmental phenotype was observed for all 24 viable mutants. We
investigated p38 mitogen-activated protein kinase (MAPK) phosphorylation profiles
in the phosphatase mutants and identified nine potential candidates for
regulators of the p38 MAPK. We demonstrated that the PP2C class phosphatase pph-8
(NCU04600) is an important regulator of female sexual development in N. crassa.
In addition, we showed that the Deltacsp-6 (DeltaNCU08380) mutant exhibits a
phenotype similar to the previously identified conidial separation mutants,
Deltacsp-1 and Deltacsp-2, that lack transcription factors important for
regulation of conidiation and the circadian clock.
PMID- 24347633
TI - Glycoxidative damage to human DNA: Neo-antigenic epitopes on DNA molecule could
be a possible reason for autoimmune response in type 1 diabetes.
AB - Advanced glycation end-products (AGEs) are known to be mutagenic, diabetogenic
and vascular disease risk factors. Methylglyoxal (MG) is a dicarbonyl species
that reacts with biological macromolecule (proteins, DNA and lipids) to give
AGEs. Nonenzymatic glycation of MG with lysine (Lys) in the presence of copper
(Cu(2+)) is reported to generate reactive oxygen species (ROS) capable of causing
DNA damage. We show that DNA modification in MG-Lys-Cu(2+) system results in the
generation of strand breaks, base modification, hyperchromicity and increased
fluorescence intensity. Superoxide generation in the MG-Lys system was found to
be significantly higher when compared with that in the MG and Lys alone.
Moreover, d-penicillamine and pyridoxal phosphate significantly inhibited the
formation of glycation products. The presence of a major DNA glycation adduct,
N(2)-carboxyethyl-2'-deoxyguanosine (CEdG), was detected by high performance
liquid chromatography (HPLC) and confirmed by nuclear magnetic resonance (NMR).
As reported earlier, modified DNA (MG-Lys-Cu(2+)-DNA) was highly immunogenic in
experimental animals. Furthermore, induced anti-MG-Lys-Cu(2+)-DNA antibodies were
effective probe for detecting glycoxidative lesions in human genomic DNA of type
I diabetes patients. Our results clearly imply that interaction of MG-Lys and
Cu(2+) leads to the formation of AGEs and also the production of potent ROS,
capable of causing DNA damage, thereby playing an important role in diabetes
mellitus.
PMID- 24347634
TI - Cumulative latency advance underlies fast visual processing in desynchronized
brain state.
AB - Fast sensory processing is vital for the animal to efficiently respond to the
changing environment. This is usually achieved when the animal is vigilant, as
reflected by cortical desynchronization. However, the neural substrate for such
fast processing remains unclear. Here, we report that neurons in rat primary
visual cortex (V1) exhibited shorter response latency in the desynchronized state
than in the synchronized state. In vivo whole-cell recording from the same V1
neurons undergoing the two states showed that both the resting and visually
evoked conductances were higher in the desynchronized state. Such conductance
increases of single V1 neurons shorten the response latency by elevating the
membrane potential closer to the firing threshold and reducing the membrane time
constant, but the effects only account for a small fraction of the observed
latency advance. Simultaneous recordings in lateral geniculate nucleus (LGN) and
V1 revealed that LGN neurons also exhibited latency advance, with a degree
smaller than that of V1 neurons. Furthermore, latency advance in V1 increased
across successive cortical layers. Thus, latency advance accumulates along
various stages of the visual pathway, likely due to a global increase of membrane
conductance in the desynchronized state. This cumulative effect may lead to a
dramatic shortening of response latency for neurons in higher visual cortex and
play a critical role in fast processing for vigilant animals.
PMID- 24347632
TI - Large-scale quality analysis of published ChIP-seq data.
AB - ChIP-seq has become the primary method for identifying in vivo protein-DNA
interactions on a genome-wide scale, with nearly 800 publications involving the
technique appearing in PubMed as of December 2012. Individually and in aggregate,
these data are an important and information-rich resource. However, uncertainties
about data quality confound their use by the wider research community. Recently,
the Encyclopedia of DNA Elements (ENCODE) project developed and applied metrics
to objectively measure ChIP-seq data quality. The ENCODE quality analysis was
useful for flagging datasets for closer inspection, eliminating or replacing poor
data, and for driving changes in experimental pipelines. There had been no
similarly systematic quality analysis of the large and disparate body of
published ChIP-seq profiles. Here, we report a uniform analysis of vertebrate
transcription factor ChIP-seq datasets in the Gene Expression Omnibus (GEO)
repository as of April 1, 2012. The majority (55%) of datasets scored as being
highly successful, but a substantial minority (20%) were of apparently poor
quality, and another ~25% were of intermediate quality. We discuss how different
uses of ChIP-seq data are affected by specific aspects of data quality, and we
highlight exceptional instances for which the metric values should not be taken
at face value. Unexpectedly, we discovered that a significant subset of control
datasets (i.e., no immunoprecipitation and mock immunoprecipitation samples)
display an enrichment structure similar to successful ChIP-seq data. This can, in
turn, affect peak calling and data interpretation. Published datasets identified
here as high-quality comprise a large group that users can draw on for large
scale integrated analysis. In the future, ChIP-seq quality assessment similar to
that used here could guide experimentalists at early stages in a study, provide
useful input in the publication process, and be used to stratify ChIP-seq data
for different community-wide uses.
PMID- 24347635
TI - Covalent EGFR inhibitor analysis reveals importance of reversible interactions to
potency and mechanisms of drug resistance.
AB - Covalent inhibition is a reemerging paradigm in kinase drug design, but the roles
of inhibitor binding affinity and chemical reactivity in overall potency are not
well-understood. To characterize the underlying molecular processes at a
microscopic level and determine the appropriate kinetic constants, specialized
experimental design and advanced numerical integration of differential equations
are developed. Previously uncharacterized investigational covalent drugs reported
here are shown to be extremely effective epidermal growth factor receptor (EGFR)
inhibitors (kinact/Ki in the range 10(5)-10(7) M(-1)s(-1)), despite their low
specific reactivity (kinact <= 2.1 * 10(-3) s(-1)), which is compensated for by
high binding affinities (Ki < 1 nM). For inhibitors relying on reactivity to
achieve potency, noncovalent enzyme-inhibitor complex partitioning between
inhibitor dissociation and bond formation is central. Interestingly, reversible
binding affinity of EGFR covalent inhibitors is highly correlated with antitumor
cell potency. Furthermore, cellular potency for a subset of covalent inhibitors
can be accounted for solely through reversible interactions. One reversible
interaction is between EGFR-Cys797 nucleophile and the inhibitor's reactive
group, which may also contribute to drug resistance. Because covalent inhibitors
target a cysteine residue, the effects of its oxidation on enzyme catalysis and
inhibitor pharmacology are characterized. Oxidation of the EGFR cysteine
nucleophile does not alter catalysis but has widely varied effects on inhibitor
potency depending on the EGFR context (e.g., oncogenic mutations), type of
oxidation (sulfinylation or glutathiolation), and inhibitor architecture. These
methods, parameters, and insights provide a rational framework for assessing and
designing effective covalent inhibitors.
PMID- 24347637
TI - Identification of secreted bacterial proteins by noncanonical amino acid tagging.
AB - Pathogenic microbes have evolved complex secretion systems to deliver virulence
factors into host cells. Identification of these factors is critical for
understanding the infection process. We report a powerful and versatile approach
to the selective labeling and identification of secreted pathogen proteins.
Selective labeling of microbial proteins is accomplished via translational
incorporation of azidonorleucine (Anl), a methionine surrogate that requires a
mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen
proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched
by affinity purification. Application of the method to analysis of the type III
secretion system of the human pathogen Yersinia enterocolitica enabled efficient
identification of secreted proteins, identification of distinct secretion
profiles for intracellular and extracellular bacteria, and determination of the
order of substrate injection into host cells. This approach should be widely
useful for the identification of virulence factors in microbial pathogens and the
development of potential new targets for antimicrobial therapy.
PMID- 24347638
TI - Salmonella exploits NLRP12-dependent innate immune signaling to suppress host
defenses during infection.
AB - The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin
domain containing 12 (NLRP12) plays a protective role in intestinal inflammation
and carcinogenesis, but the physiological function of this NLR during microbial
infection is largely unexplored. Salmonella enterica serovar Typhimurium (S.
typhimurium) is a leading cause of food poisoning worldwide. Here, we show that
NLRP12-deficient mice were highly resistant to S. typhimurium infection.
Salmonella-infected macrophages induced NLRP12-dependent inhibition of NF-kappaB
and ERK activation by suppressing phosphorylation of IkappaBalpha and ERK. NLRP12
mediated down-regulation of proinflammatory and antimicrobial molecules prevented
efficient clearance of bacterial burden, highlighting a role for NLRP12 as a
negative regulator of innate immune signaling during salmonellosis. These results
underscore a signaling pathway defined by NLRP12-mediated dampening of host
immune defenses that could be exploited by S. typhimurium to persist and survive
in the host.
PMID- 24347639
TI - Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair.
AB - The cellular response to highly genotoxic DNA double-strand breaks (DSBs)
involves the exquisite coordination of multiple signaling and repair factors.
Here, we conducted a functional RNAi screen and identified BAP1 as a
deubiquitinase required for efficient assembly of the homologous recombination
(HR) factors BRCA1 and RAD51 at ionizing radiation (IR) -induced foci. BAP1 is a
chromatin-associated protein frequently inactivated in cancers of various
tissues. To further investigate the role of BAP1 in DSB repair, we used a gene
targeting approach to knockout (KO) this deubiquitinase in chicken DT40 cells. We
show that BAP1-deficient cells are (i) sensitive to IR and other agents that
induce DSBs, (ii) defective in HR-mediated immunoglobulin gene conversion, and
(iii) exhibit an increased frequency of chromosomal breaks after IR treatment. We
also show that BAP1 is recruited to chromatin in the proximity of a single site
specific I-SceI-induced DSB. Finally, we identified six IR-induced
phosphorylation sites in BAP1 and showed that mutation of these residues inhibits
BAP1 recruitment to DSB sites. We also found that both BAP1 catalytic activity
and its phosphorylation are critical for promoting DNA repair and cellular
recovery from DNA damage. Our data reveal an important role for BAP1 in DSB
repair by HR, thereby providing a possible molecular basis for its tumor
suppressor function.
PMID- 24347641
TI - The elephant, the blind, and the intersectoral intercomparison of climate
impacts.
PMID- 24347640
TI - Dual-modality gene reporter for in vivo imaging.
AB - The ability to track cells and their patterns of gene expression in living
organisms can increase our understanding of tissue development and disease. Gene
reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance
imaging (MRI) have been described but these suffer variously from limited depth
penetration, spatial resolution, and sensitivity. We describe here a gene
reporter, based on the organic anion transporting protein Oatp1a1, which mediates
uptake of a clinically approved, Gd(3+)-based, hepatotrophic contrast agent
(gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing
the reporter showed readily reversible, intense, and positive contrast (up to 7.8
fold signal enhancement) in T1-weighted magnetic resonance images acquired in
vivo. The maximum signal enhancement obtained so far is more than double that
produced by MRI gene reporters described previously. Exchanging the Gd(3+) ion
for the radionuclide, (111)In, also allowed detection by single-photon emission
computed tomography, thus combining the spatial resolution of MRI with the
sensitivity of radionuclide imaging.
PMID- 24347642
TI - A Cdc42- and Rac-interactive binding (CRIB) domain mediates functions of coronin.
AB - The Cdc42- and Rac-interactive binding motif (CRIB) of coronin binds to Rho
GTPases with a preference for GDP-loaded Rac. Mutation of the Cdc42- and Rac
interactive binding motif abrogates Rac binding. This results in increased 1evels
of activated Rac in coronin-deficient Dictyostelium cells (corA(-)), which
impacts myosin II assembly. corA(-) cells show increased accumulation of myosin
II in the cortex of growth-phase cells. Myosin II assembly is regulated by myosin
heavy chain kinase-mediated phosphorylation of its tail. Kinase activity depends
on the activation state of the p21-activated kinase a. The myosin II defect of
corA(-) mutant is alleviated by dominant-negative p21-activated kinase a. It is
rescued by wild-type coronin, whereas coronin carrying a mutated Cdc42- and Rac
interactive binding motif failed to rescue the myosin defect in corA(-) mutant
cells. Ectopically expressed myosin heavy chain kinases affinity purified from
corA(-) cells show reduced kinase activity. We propose that coronin through its
affinity for GDP-Rac regulates the availability of GTP-Rac for activation of
downstream effectors.
PMID- 24347645
TI - Absence of splash singularities for surface quasi-geostrophic sharp fronts and
the Muskat problem.
AB - In this paper, for both the sharp front surface quasi-geostrophic equation and
the Muskat problem, we rule out the "splash singularity" blow-up scenario; in
other words, we prove that the contours evolving from either of these systems
cannot intersect at a single point while the free boundary remains smooth. Splash
singularities have been shown to hold for the free boundary incompressible Euler
equation in the form of the water waves contour evolution problem. Our result
confirms the numerical simulations in earlier work, in which it was shown that
the curvature blows up because the contours collapse at a point. Here, we prove
that maintaining control of the curvature will remove the possibility of
pointwise interphase collapse. Another conclusion that we provide is a better
understanding of earlier work in which squirt singularities are ruled out; in
this case, a positive volume of fluid between the contours cannot be ejected in
finite time.
PMID- 24347646
TI - Greenland Pt anomaly may point to noncataclysmic Cape York meteorite entry.
PMID- 24347643
TI - Spontaneous slow replication fork progression elicits mitosis alterations in
homologous recombination-deficient mammalian cells.
AB - Homologous recombination deficient (HR(-)) mammalian cells spontaneously display
reduced replication fork (RF) movement and mitotic extra centrosomes. We show
here that these cells present a complex mitotic phenotype, including prolonged
metaphase arrest, anaphase bridges, and multipolar segregations. We then asked
whether the replication and the mitotic phenotypes are interdependent. First, we
determined low doses of hydroxyurea that did not affect the cell cycle
distribution or activate CHK1 phosphorylation but did slow the replication fork
movement of wild-type cells to the same level than in HR(-) cells. Remarkably,
these low hydroxyurea doses generated the same mitotic defects (and to the same
extent) in wild-type cells as observed in unchallenged HR(-) cells. Reciprocally,
supplying nucleotide precursors to HR(-) cells suppressed both their replication
deceleration and mitotic extra centrosome phenotypes. Therefore, subtle
replication stress that escapes to surveillance pathways and, thus, fails to
prevent cells from entering mitosis alters metaphase progression and centrosome
number, resulting in multipolar mitosis. Importantly, multipolar mitosis results
in global unbalanced chromosome segregation involving the whole genome, even
fully replicated chromosomes. These data highlight the cross-talk between
chromosome replication and segregation, and the importance of HR at the interface
of these two processes for protection against general genome instability.
PMID- 24347647
TI - Development of a Croatian version of the US Hospital Survey on Patient Safety
Culture questionnaire: dimensionality and psychometric properties.
AB - BACKGROUND: The Hospital Survey on Patient Safety Culture (HSOPSC), originally
developed in the USA, is used worldwide to assess patient safety culture in
hospitals. A limited number of studies have provided data on psychometric
properties outside of the US healthcare system. Our aim was to determine if all
12 dimensions of the US HSOPSC were applicable, valid and reliable to Croatian
healthcare workers. METHODS: The study was conducted from September 2010 to April
2011. Questions were translated into Croatian and then translated back into
English. The questionnaires (ie, the Croatian translation of the US HSOPSC) were
distributed in unmarked envelopes along with a consent form to all the doctors
and nurses in four Croatian hospitals. The responses were analysed using
explorative factor analyses, reliability testing, and confirmatory factor
analyses. RESULTS: The study included 561 healthcare workers in four Croatian
hospitals--a response rate of 32.69%. Our results are similar to the original US
sample, but with some differences: 11 dimensions with acceptable reliability
scores were identified by exploratory factor analysis compared with the original
12 in the US sample; five of 12 dimensions had a Cronbach's alpha higher than
0.7, suggesting a reasonable fit to the original US HSOPSC; the dimensions
'Staffing' and 'Organisational learning--continuous improvement' were found to
have a Cronbach's alpha <0.6. The use of confirmatory factor analysis confirmed a
good fit to the original US model. CONCLUSIONS: Results show that the Croatian
translation of the US HSOPSC is compatible in 11 of the original 12 dimensions.
Results suggest that for the purposes of research in Croatia, the dimensions
'Staffing', 'Communication openness', and 'Organisational learning-continuous
improvement' should be revised. For example, the use of question A7 ('We use more
agency/temporary staff than is best for patient care') in the context of European
healthcare systems should be adapted or removed for the Croatian version of the
US HSOPSC questionnaire.
PMID- 24347648
TI - Deterioration following craniectomy.
PMID- 24347649
TI - Oral antibiotics at discharge for children with acute osteomyelitis: a rapid
cycle improvement project.
AB - BACKGROUND: Substantial evidence demonstrates comparable cure rates for oral
versus intravenous therapy for routine osteomyelitis. Evidence adoption is often
slow and in our centre virtually all patients with osteomyelitis were discharged
on intravenous therapy. OBJECTIVE: For patients with acute osteomyelitis admitted
to the hospital medicine service, we aimed to increase the proportion of cases
discharged on oral antibiotics to at least 70%. METHODS: The setting for our
observational time series study was a large academic children's hospital. The
model for improvement and plan-do-study-act cycles were used to test, refine and
implement interventions identified through our key driver diagram. Our
multifaceted intervention included a shared decision-making tool, an order set in
our electronic health record, and education to faculty and trainees. We also
included an identify and mitigate intervention to target providers caring for
children with osteomyelitis in near-real time and reinforce the evidence-based
recommendations. Data were analysed on an annotated g-chart of osteomyelitis
cases between patients discharged on intravenous antibiotics. Structured chart
review was used to identify treatment failures as well as length of stay and
hospital charges in preintervention and postintervention groups. RESULTS: The
osteomyelitis cases between patients discharged on intravenous antibiotics
increased from a median of 0 preintervention to a maximum of 9 cases following
our identify and mitigate intervention. The direction and magnitude of successive
improvements observed satisfied criteria for special cause variation. Improvement
has been sustained for 1 year. Treatment failure and complications were uncommon
in preintervention and postintervention phases. No significant differences in
length of stay or charges were detected. CONCLUSIONS: Even for uncommon
conditions, rapid and sustained evidence adoption is possible using quality
improvement methods.
PMID- 24347651
TI - Effect of locally applied transforming growth factor Beta3 on wound healing and
stenosis development in tracheal surgery.
AB - BACKGROUND: Tracheal stenosis constitutes one of the most frequently seen
problems in thoracic surgery. Although many treatment modalities to prevent
fibroblast proliferation, angiogenesis, or inflammation that causes tracheal
stenosis have been attempted, an effective method has not yet been found. In this
study, a transforming growth factor beta3 (TGF-beta3)/chitosan combination was
used for this purpose. METHODS: A slow-release preparation containing a thin
layer of TGF-beta3 with a chitosan base was made. Thirty albino Wistar rats were
divided into 3 groups. A full-layer vertical incision was made in the anterior
side of the trachea of each rat between the second and fifth tracheal rings. The
tracheal incision was sutured. Group A was evaluated as the control group. In
Group B, a chitosan-based film was placed on the incision line. In Group C, a
slow-release TGF-beta3/chitosan-coated substance was placed on the incision line.
The rats were killed on day 30, and their tracheas were excised by cutting
between the lower edge of the thyroid cartilage and the upper edge of the sixth
tracheal ring together with the esophagus. Epithelialization, fibroblast
proliferation, angiogenesis, inflammation, and collagen levels were evaluated
histopathologically by the same histopathologist. RESULTS: Statistically
significant differences were not found among the 3 groups. Cold abscesses were
observed at the incision sites in both the TGF-beta/chitosan and chitosan groups.
These were thought to have formed due to the chitosan. CONCLUSIONS: As this was
the first experiment in the literature to use this type of TGF-beta3 formulation,
we intend to change the formulation and perform this study again with a different
TGF-beta3/chitosan preparation.
PMID- 24347650
TI - Caring for critically ill children in the community: a needs assessment.
AB - OBJECTIVE: The goal of this study was to identify barriers and facilitators to
the optimal management of critically ill children who present initially to
community hospitals and how best to support the needs of front-line healthcare
providers in these settings prior to transfer to the regional academic paediatric
health sciences centre. METHODS: A qualitative needs assessment was performed in
five community hospitals targeting healthcare providers in leadership and front
line roles who could discuss their experiences of managing critically ill
children that had presented to their institutions. Focused individual and focus
group interviews of physicians, nurses and respiratory therapists from the
participating hospitals were conducted and analysed to identify common themes.
RESULTS: Five community hospitals participated in the study with a total of 57
participants and included 36 registered nurses, 4 respiratory therapists, 13
community hospital physicians and 4 paediatric intensive care specialists. Most
participants did not report seeing more than one critically ill child per month.
The management of very young paediatric patients was reported as a greater source
of anxiety than patients presenting in cardiac arrest and despite being more
frequently reported, respiratory conditions were identified as the most anxiety
provoking and having the greatest educational need. The care required for a
single critically ill child was often reported to render the emergency department
staff incapable of meeting other patient care needs and was influenced by
staffing resources, physical layout and access to proper equipment. Increased
comfort and management ability was attributed to previous real-world experience
and support from content experts in dealing with acutely ill children.
Participants did not use web-based best practice guidelines. CONCLUSIONS: This
study identifies the need to fully understand the management realities of front
line caregivers of critically ill children in community hospital settings. We
demonstrate the need to focus on the management of younger paediatric patients,
technical skills development, practice of acute situations with less than optimal
staffing resources, and access to facilitated real-world experiences with
appropriate supervision and mentoring. Passive interventions such as web-based
guidelines should not be used in isolation but as a support to ongoing exposure
and engagement by content experts.
PMID- 24347652
TI - Hyperinflation on chest radiograph as a marker of low adherence to positive
airway pressure therapy in the overlap syndrome.
AB - BACKGROUND: Positive airway pressure (PAP) in subjects with both obstructive
sleep apnea and COPD reduces the risk of pulmonary hypertension, death, and
hospitalizations from COPD exacerbations, but adherence to the intervention is
low, similar to the experience with noninvasive ventilation in stable COPD. We
sought to assess whether hyperinflation on chest radiographs contributes to low
adherence to PAP therapy in the overlap syndrome. METHODS: Records of patients
with a listed diagnosis of COPD at the time of polysomnography were reviewed.
Overlap syndrome was diagnosed when COPD was clinically confirmed with spirometry
showing a fixed airway obstruction and when the apnea-hypopnea index was >= 5.
Hyperinflation was evaluated by a review of the right diaphragm height on a
lateral chest radiograph. Adherence was assessed clinically or through device
download at a 3-month follow-up, and later adherence was assessed by telephone
interviews. A receiver operating curve was used to determine whether diaphragm
height was associated with adherence. RESULTS: Twenty-one of 41 subjects (51%)
were considered adherent to PAP therapy at the 3-month visit. Adherent subjects
were more overweight compared with non-adherent subjects (body mass index of 36.0
+/- 5.7 vs 32.0 +/- 5.7 kg/m(2), P = .03), sleepier at the onset (Epworth
sleepiness scale score of 13.0 +/- 5.8 vs 9.4 +/- 5.4, P < .05), and less likely
to have hyperinflation as defined by a right diaphragm height <= 2.45 cm (33% vs
65%, P = .04). The body mass index and initial sleepiness no longer predicted
adherence beyond 3 months, but 35% of subjects with a right diaphragm height <=
2.45 cm were adherent beyond 3 months compared with 75% of those with a right
diaphragm height > 2.45 cm (P = .04 by Fisher exact test). CONCLUSIONS:
Hyperinflation is associated with decreased adherence to PAP therapy in the
overlap syndrome.
PMID- 24347653
TI - Percutaneous coronary interventions in ST-segment-elevation myocardial
infarction: shifting paradigms and future perspectives.
PMID- 24347654
TI - Transcatheter aortic valve replacement in patients with aortic stenosis and left
ventricular dysfunction: patient selection counts more than ever!
PMID- 24347655
TI - Neurological injury after transcatheter aortic valve implantation: are the trees
falling silently or is our hearing impaired?
PMID- 24347656
TI - Standardized hyperemic stress for fractional flow reserve.
PMID- 24347657
TI - Assessment and impact of the human coronary collateral circulation on myocardial
ischemia and outcome.
PMID- 24347658
TI - Aortopulmonary fistula after transcatheter pulmonary valve replacement.
PMID- 24347661
TI - Changes in geographic variation in the use of percutaneous coronary intervention
for stable ischemic heart disease after publication of the Clinical Outcomes
Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.
AB - BACKGROUND: Clinical uncertainty is cited as a cause of geographic variation.
However, little is known about the effect of comparative effectiveness research
on variation. We examined whether geographic variation in the use of percutaneous
coronary intervention (PCI) for stable ischemic heart disease (SIHD) declined
after publication of the Clinical Outcomes Utilizing Revascularization and
Aggressive Drug Evaluation (COURAGE) trial. METHODS AND RESULTS: We examined
changes in utilization and geographic variation in 67 hospital referral regions
using the State Inpatient Databases. We compared age- and sex-adjusted rates of
PCI for SIHD before (2006) and after (2008) publication of the COURAGE trial and
compared those with contemporaneous changes in PCI volume for acute coronary
syndrome. A total of 272,659 PCIs for SIHD from 526 hospitals were included in
the analysis. After the publication of the COURAGE trial, PCI volume for SIHD
declined by 25% (P<0.001) and decreased by 12% for acute coronary syndrome
(P<0.001). This was predominantly attributable to changes in hospital referral
regions with the highest levels of utilization pre-COURAGE trial (35% decline in
the highest tertile versus 18% in the lowest). As measured by the systematic
component of variation, there was substantial geographic variation in the use of
PCI for SIHD preceding the publication of the COURAGE trial. Variation declined
by 28% (0.53 versus 0.40) after publication, but geographic variation remained
higher for SIHD than acute coronary syndrome (0.40 versus 0.17). CONCLUSIONS:
There was a substantial decline in the use of and geographic variation in PCI for
SIHD after the publication of the COURAGE trial. However, geographic variation in
the use of PCI for SIHD remained high.
PMID- 24347662
TI - Women in cardiology: introspection into the under-representation.
PMID- 24347663
TI - Prognostic value of plasma neutrophil gelatinase-associated lipocalin for
mortality in patients with heart failure.
AB - BACKGROUND: In patients with heart failure, renal dysfunction is associated with
a poor outcome. We aimed to assess the prognostic value of plasma neutrophil
gelatinase-associated lipocalin (NGAL), a novel marker of renal tubular damage,
in patients with heart failure with or without renal dysfunction, and compare it
with 2 frequently used biomarkers of chronic kidney disease. METHODS AND RESULTS:
Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were
assessed in 562 patients with heart failure. Chronic kidney disease was defined
as eGFR<60 mL/min per 1.73 m2. Outcome was all-cause mortality at 36 months. Mean
age was 71+/-11 years, 61% were men, and 97% were in New York Heart Association
functional class II/III. Mean baseline eGFR was 54+/-20 mL/min per 1.73 m2, mean
cystatin C was 11.2 (7.7-16.2) mg/L, and median plasma NGAL was 85 (60-123)
ng/mL. Higher plasma NGAL levels were independently associated with an increased
risk of all-cause mortality, in patients with and without chronic kidney disease
(hazard ratio [per SD increase in log NGAL]=1.45 [1.22-1.72]; P<0.001 and hazard
ratio=1.51 [1.06-2.16]; P=0.023, respectively). Similarly, both in patients with
high and low cystatin C (median cut-off), higher plasma NGAL levels were
independently associated with an increased risk of all-cause mortality. Moreover,
when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616)
and cystatin C (P=0.937) were no longer associated with mortality. CONCLUSIONS:
Plasma NGAL predicts mortality in patients with heart failure, both in patients
with and without chronic kidney disease and is a stronger predictor for mortality
than the established renal function indices eGFR and cystatin C.
PMID- 24347664
TI - Left atrial volume and the benefit of cardiac resynchronization therapy in the
MADIT-CRT trial.
AB - BACKGROUND: Left atrial volume (LAV) is an important marker of heart failure (HF)
severity. We hypothesized that LAV independently correlates with clinical
outcomes in patients who receive cardiac resynchronization therapy with a
defibrillator (CRT-D) and can be used for improved risk assessment in this
population. METHODS AND RESULTS: The benefit of CRT-D versus defibrillator-only
therapy in reducing the risk of HF or death was assessed by LAV (dichotomized at
the upper quartile>52 mL/m2) among 1785 patients enrolled in the Multicenter
Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy
(MADIT-CRT) study. Landmark analysis was used to evaluate the relationship
between LAV response to CRT-D and subsequent clinical outcomes. Multivariable
analysis showed that patients with a higher baseline LAV experienced 69%
(P<0.001) and 59% (P=0.02) increased hazard for HF or death and for all-cause
mortality, respectively, independently of baseline left ventricular volume. CRT-D
was associated with a significant reduction in LAV compared with defibrillator
only therapy (-28% versus -10%, respectively; P<0.001). Landmark analysis showed
that after CRT-D implantation each 1% reduction in LAV was independently
associated with a corresponding 4% reduction in the hazard of subsequent HF or
death (P<0.001). The assessment of LAV change after CRT implantation improved
prediction of clinical response to the device compared with assessment of the
corresponding changes in left ventricular volume. CONCLUSIONS: LAV is an
independent correlate of clinical outcomes in mildly symptomatic HF patients
treated with CRT-D. CRT exerts pronounced reverse remodeling effects on the left
atrium that independently correlate with improved clinical outcomes after device
implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
Unique identifier: NCT00180271.
PMID- 24347665
TI - Inflammation and mechanical stretch promote aortic stiffening in hypertension
through activation of p38 mitogen-activated protein kinase.
AB - RATIONALE: Aortic stiffening commonly occurs in hypertension and further elevates
systolic pressure. Hypertension is also associated with vascular inflammation and
increased mechanical stretch. The interplay between inflammation, mechanical
stretch, and aortic stiffening in hypertension remains undefined. OBJECTIVE: Our
aim was to determine the role of inflammation and mechanical stretch in aortic
stiffening. METHODS AND RESULTS: Chronic angiotensin II infusion caused marked
aortic adventitial collagen deposition, as quantified by Masson trichrome blue
staining and biochemically by hydroxyproline content, in wild-type but not in
recombination activating gene-1-deficient mice. Aortic compliance, defined by ex
vivo measurements of stress-strain curves, was reduced by chronic angiotensin II
infusion in wild-type mice (P<0.01) but not in recombination activating gene-1
deficient mice (P<0.05). Adoptive transfer of T-cells to recombination activating
gene-1-deficient mice restored aortic collagen deposition and stiffness to values
observed in wild-type mice. Mice lacking the T-cell-derived cytokine interleukin
17a were also protected against aortic stiffening. In additional studies, we
found that blood pressure normalization by treatment with hydralazine and
hydrochlorothiazide prevented angiotensin II-induced vascular T-cell
infiltration, aortic stiffening, and collagen deposition. Finally, we found that
mechanical stretch induces the expression of collagen 1alpha1, 3alpha1, and 5a1
in cultured aortic fibroblasts in a p38 mitogen-activated protein kinase
dependent fashion, and that inhibition of p38 prevented angiotensin II-induced
aortic stiffening in vivo. Interleukin 17a also induced collagen 3a1 expression
via the activation of p38 mitogen-activated protein kinase. CONCLUSIONS: Our data
define a pathway in which inflammation and mechanical stretch lead to vascular
inflammation that promotes collagen deposition. The resultant increase in aortic
stiffness likely further worsens systolic hypertension and its attendant end
organ damage.
PMID- 24347666
TI - Racism and Health I: Pathways and Scientific Evidence.
AB - This article reviews the scientific research that indicates that despite marked
declines in public support for negative racial attitudes in the United States,
racism, in its multiple forms, remains embedded in American society. The focus of
the article is on the review of empirical research that suggests that racism
adversely affects the health of non-dominant racial populations in multiple ways.
First, institutional racism developed policies and procedures that have reduced
access to housing, neighborhood and educational quality, employment opportunities
and other desirable resources in society. Second, cultural racism, at the
societal and individual level, negatively affects economic status and health by
creating a policy environment hostile to egalitarian policies, triggering
negative stereotypes and discrimination that are pathogenic and fostering health
damaging psychological responses such as stereotype threat and internalized
racism. Finally, a large and growing body of evidence indicates that experiences
of racial discrimination are an important type of psychosocial stressor that can
lead to adverse changes in health status and altered behavioural patterns that
increase health risks.
PMID- 24347668
TI - A Note on Comparing the Power of Test Statistics at Low Significance Levels.
AB - It is an obvious fact that the power of a test statistic is dependent upon the
significance (alpha) level at which the test is performed. It is perhaps a less
obvious fact that the relative performance of two statistics in terms of power is
also a function of the alpha level. Through numerous personal discussions, we
have noted that even some competent statisticians have the mistaken intuition
that relative power comparisons at traditional levels such as alpha = 0.05 will
be roughly similar to relative power comparisons at very low levels, such as the
level alpha = 5 * 10-8, which is commonly used in genome-wide association
studies. In this brief note, we demonstrate that this notion is in fact quite
wrong, especially with respect to comparing tests with differing degrees of
freedom. In fact, at very low alpha levels the cost of additional degrees of
freedom is often comparatively low. Thus we recommend that statisticians exercise
caution when interpreting the results of power comparison studies which use alpha
levels that will not be used in practice.
PMID- 24347667
TI - Racism and Health II: A Needed Research Agenda for Effective Interventions.
AB - This article reviews the empirical evidence that suggests that there is a solid
foundation for more systematic research attention to the ways in which
interventions that seek to reduce the multiple dimensions of racism can improve
health and reduce disparities in health. First, research reveals that policies
and procedures that seek to reduce institutional racism by improving neighborhood
and educational quality and enhancing access to additional income, employment
opportunities and other desirable resources can improve health. Second, research
is reviewed that shows that there is the potential to improve health through
interventions that can reduce cultural racism at the societal and individual
level. Finally, research is presented that suggests that the adverse consequences
of racism on health can be reduced through policies that maximize the health
enhancing capacities of medical care, address the social factors that initiate
and sustain risk behaviors and empower individuals and communities to take
control of their lives and health. Directions for future research are outlined.
PMID- 24347669
TI - Parasitoid infestation changes female mating preferences.
AB - Females often adjust their mating preference to environmental and social
conditions. This plasticity of preference can be adaptive for females and can
have important consequences for the evolution of male traits. While predation and
parasitism are widespread, their effects on female preferences have rarely been
investigated. Females of the cricket Gryllus lineaticeps are parasitized by the
parasitoid fly Ormia ochracea. Infestation with fly larvae substantially reduces
female life span and thus reproductive opportunities of the cricket. Both female
G. lineaticeps and flies orient to male song and both prefer male songs with
faster chirp rates to songs with slower chirp rates. We tested the effect of
parasitic infestation on female responsiveness to male song and female chirp rate
preferences. The proportion of individuals responding to male songs did not
differ between infested and control females. Control females preferred
intermediate chirp rates to slow chirp rates and did not discriminate between
fast and intermediate chirp rates. In contrast, infested females showed no
preferences in the choice trials, indicating reduced chirp rate selectivity. This
plasticity in female preferences may be adaptive; parasitized females may have a
higher probability of reproducing before they are killed by the parasitoids if
they are less selective (i.e. there will be a larger pool of males considered
acceptable). The change in preferences suggests relaxed selection on male chirp
rate during times of parasitism.
PMID- 24347670
TI - Well, Now, Okey Dokey: English Discourse Markers in Spanish Language Medical
Consultations.
AB - The purpose of this paper is to examine use of English discourse markers in
otherwise Spanish language consultations. Data is derived from an audio-recorded
corpus of Spanish language consultations that took place in a small community
clinic in the United States as well as post-consultation interviews with patients
and providers. Through quantification of the use of discourse makers in the
corpus and discourse analysis of transcripts, we demonstrate that English
speaking dominant medical providers use English discourse markers more frequently
and with a broader range of functions than do Spanish-speaking dominant medical
providers and patients. We argue that such use of English discourse markers
serves to exacerbate the power relationship between providers and patients even
though the use of English discourse markers does not cause overt miscommunication
in the ongoing interaction. Implications for providers who use a second language
in their medical consultations are discussed.
PMID- 24347671
TI - Nitroxide-Functionalized Graphene Oxide from Graphite Oxide.
AB - A facile method for preparing functionalized graphene oxide single layers with
nitroxide groups is reported herein. Highly oxidized graphite oxide (GO=90.6%)
was obtained, slightly modifying an improved Hummer's method. Oxoammonium salts
(OS) were investigated to introduce nitroxide groups to GO, resulting in a one
step functionalization and exfoliation. The mechanisms of
functionalization/exfoliation are proposed, where the oxidation of aromatic
alcohols to ketone groups, and the formation of alkoxyamine species are
suggested. Two kinds of functionalized graphene oxide layers (GOFT1 and GOFT2)
were obtained by controlling the amount of OS added. GOFT1 and GOFT2 exhibited a
high interlayer spacing (d0001 = 1.12nm), which was determined by X-ray
diffraction. The presence of new chemical bonds C-N (~9.5 %) and O-O (~4.3 %)
from nitroxide attached onto graphene layers were observed by X-ray photoelectron
spectroscopy. Single-layers of GOFT1 were observed by HRTEM, exhibiting amorphous
and crystalline zones at a 50:50 ratio; in contrast, layers of GOFT2 exhibited a
fully amorphous surface. Fingerprint of GOFT1 single layers was obtained by
electron diffraction at several tilts. Finally, the potential use of these
materials within Nylon 6 matrices was investigated, where an unusual simultaneous
increase in tensile stress, tensile strain and Young's modulus was observed.
PMID- 24347672
TI - Coaxial electrohydrodynamic atomization process for production of polymeric
composite microspheres.
AB - Polymeric composite microspheres consisting of a poly(D,L-lactic-co-glycolic
acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer were
successfully fabricated by coaxial electrohydrodynamic atomization (CEHDA)
process. Process conditions, including nozzle voltage and polymer solution flow
rates, as well as solution parameters, such as polymer concentrations, were
investigated to ensure the formation of composite microspheres with a doxorubicin
loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Various
microsphere formulations were fabricated and characterized in terms of their drug
distribution, encapsulation efficiency and in vitro release. Numerical simulation
of CEHDA process was performed based on a computational fluid dynamics (CFD)
model in Fluent by employing the process conditions and fluid properties used in
the experiments. The simulation results were compared with the experimental work
to illustrate the capability of the CFD model to predict the production of
consistent compound droplets, and hence, the expected core-shell structured
microspheres.
PMID- 24347673
TI - Analyses of mineral specific surface area and hydroxyl substitution for intact
bone.
AB - Bone minerals possess two primary hydrogen sources: hydroxide ions in the
nanocrystalline core and structural water in the amorphous surface layer. In
order to accurately measure their concentrations using hydrogen to phosphorus
cross polarization NMR spectroscopy, it is necessary to analyze the dependence of
signal intensities on serial contact times, namely, cross polarization kinetics.
A reliable protocol is developed to iteratively decompose the severely overlapped
spectra and to analyze the cross-polarization kinetics, leading to measurement of
hydroxyl and structural water concentrations. Structural water concentration is
used to estimate mineral specific surface area and nanocrystal thickness for
intact bone.
PMID- 24347674
TI - Identity, Stress, and Resilience in Lesbians, Gay Men, and Bisexuals of Color.
AB - The author addresses two issues raised in Moradi, DeBlaere, and Huang's Major
Contribution to this issue: the intersection of racial/ethnic and lesbian, gay,
and bisexual (LGB) identities and the question of stress and resilience. The
author expands on Moradi et al.'s work, hoping to encourage further research. On
the intersection of identities, the author notes that LGB identities among people
of color have been construed as different from the identities of White LGB
persons, purportedly because of an inherent conflict between racial/ethnic and
gay identities. The author suggests that contrary to this, LGB people of color
can have positive racial/ethnic and LGB identities. On the question of stress and
resilience, hypotheses have suggested that compared with White LGB individuals,
LGB people of color have both more stress and more resilience. The author
addresses the competing hypotheses within the larger perspective of minority
stress theory, noting that the study of stress and resilience among LGB people of
color is relevant to core questions about social stress as a cause of mental
disorders.
PMID- 24347675
TI - Deforestation Drivers: Population, Migration, and Tropical Land Use.
PMID- 24347676
TI - Resolution Properties of a Prototype Continuous Miniature Crystal Element (cMiCE)
Scanner.
AB - Continuous miniature crystal element (cMiCE) detectors are a potentially lower
cost alternative for high resolution discrete crystal PET detector designs. We
report on performance characteristics of a prototype PET scanner consisting of
two cMiCE detector modules. Each cMiCE detector is comprised of a 50 * 50 * 8 mm3
LYSO crystal coupled to a 64 channel multi-anode PMT. The cMiCE detectors use a
statistics-based positioning method based upon maximum likelihood estimation for
event positioning. By this method, cMiCE detectors can also provide some depth of
interaction event positioning information. For the prototype scanner, the cMiCE
detectors were positioned across from one another on a horizontal gantry with a
detector spacing of 10.7 cm. Full tomographic data were collected and
reconstructed using single slice rebinning and filtered back projection with no
smoothing. The average image resolutions in X (radial), Y (transverse) and Z
(axial) were 1.05 +/- 0.08 mm, 0.99 +/- 0.07 mm, 1.24 +/- 0.31 mm FWHM. These
initial imaging results from a prototype imaging system demonstrate the
outstanding image resolution performance that can be achieved using the
potentially lower cost cMiCE detectors.
PMID- 24347678
TI - Movement between Mexico and Canada: Analysis of a New Migration Stream.
AB - In this analysis we use data from the Mexican Migration Project to contrast
processes of Mexican migration to Canada and the United States. All migrants to
Canada entered through the Seasonal Agricultural Worker Program and consistent
with program criteria, migration there is strongly predicted by marital status
and number of dependents, yielding a migrant population that is made up of males
of prime labor-force age who are married and have multiple children at home. In
contrast, the vast majority of migrants to the United States are undocumented and
thus self-selected without regard to marital status or parenthood. Migration to
the United States is strongly predicted by age, and migration probabilities
display the age curve classically associated with labor migration. Within
countries of destination, migrants to Canada enjoy superior labor market outcomes
compared with those to the United States, with higher wages and more compact work
schedules that yield higher earnings and shorter periods away from families
compared with undocumented migrants to the United States. Labor migration to
Canada also tends to operate as a circular flow with considerable repeat
migration whereas undocumented migrants to the United States do not come and go
so regularly, as crossing the Mexico-U.S. border has become increasingly
difficult and costly.
PMID- 24347677
TI - Finding Optimized Conditions of Slit-Slat and Multislit-Slat Collimation for
Breast Imaging.
AB - In order to develop a breast-imaging system for Single Photon Emission Computed
Tomography (SPECT) using slit-slat and multislit-slat collimators, we searched
for optimized geometric parameters of the collimators. For this study, we
employed two independent metrics to validate each result: 1) Signal to Noise
Ratio (SNR) based on the Cramer-Rao lower Bound (CRB) and 2) contrast at the same
noise level from an ensemble. We calculated SNR values using forward-projection
data of an anthropomorphic digital phantom containing two lesions in the breast
(one at the chest wall and the other at the center) with a simulated slit-slat
collimator as a function of the collimator's geometric parameters. We also
calculated contrast values from reconstructed images with noise. Based on the
results from the slit-slat case, we investigated angular range, SNR, and contrast
for the multislit-slat. We saw similar trends of the two metrics. One interesting
property of the multislit-slat is that the imaging performance depends on the
orientation of the field of view (FOV) of the side slits. When we compared the
metric values for the slit-slat and multislit-slat, improvement was seen only
when the lesion was in the FOV of the side slits. Therefore, tuning the
parameters of the multislit-slat to optimally detect lesions at the chest wall
might be a sensible option since the slit-slat already provides good image
quality for center and superficial lesions.
PMID- 24347679
TI - Narrative versus Non-narrative: The Role of Identification, Transportation and
Emotion in Reducing Health Disparities.
AB - This research empirically tests whether using a fictional narrative produces a
greater impact on health-related knowledge, attitudes, and behavioral intention
than presenting the identical information in a more traditional, nonfiction, non
narrative format. European American, Mexican American, and African American women
(N = 758) were surveyed before and after viewing either a narrative or non
narrative cervical cancer-related film. The narrative was more effective in
increasing cervical cancer-related knowledge and attitudes. Moreover, in response
to the narrative featuring Latinas, Mexican Americans were most transported,
identified most with the characters, and experienced the strongest emotions.
Regressions revealed that transportation, identification with specific
characters, and emotion each contributed to shifts in knowledge, attitudes, and
behavioral intentions. Thus, narrative formats may provide a valuable tool in
reducing health disparities.
PMID- 24347681
TI - Locomotion concerns with moral usefulness: When liberals endorse binding moral
foundations.
AB - Moral Foundations Theory has provided a framework for understanding the
endorsement of different moral beliefs. Our research investigated whether there
are other reasons to endorse moral foundations in addition to epistemic concerns;
specifically, the perceived social usefulness of moral foundations. In Study 1,
we demonstrate that those showing stronger locomotion concerns for controlling
movement tend toward a higher endorsement of binding foundations, and that this
effect is stronger among political liberals who otherwise do not typically
endorse these foundations. In Study 2, we show that priming participants with
assessment concerns (emphasizing truth) rather than locomotion concerns
(emphasizing control) reduces the response variance among liberals and also
removes the association between locomotion and the binding foundations. In Study
3, we directly ask participants to focus on moral truth versus moral usefulness,
with moral truth replicating the Study 2 effect of assessment priming, and moral
usefulness replicating the effect of locomotion priming.
PMID- 24347680
TI - A Bidirectional Coupling Procedure Applied to Multiscale Respiratory Modeling.
AB - In this study, we present a novel multiscale computational framework for
efficiently linking multiple lower-dimensional models describing the distal lung
mechanics to imaging-based 3D computational fluid dynamics (CFD) models of the
upper pulmonary airways in order to incorporate physiologically appropriate
outlet boundary conditions. The framework is an extension of the Modified
Newton's Method with nonlinear Krylov accelerator developed by Carlson and Miller
[1, 2, 3]. Our extensions include the retention of subspace information over
multiple timesteps, and a special correction at the end of a timestep that allows
for corrections to be accepted with verified low residual with as little as a
single residual evaluation per timestep on average. In the case of a single
residual evaluation per timestep, the method has zero additional computational
cost compared to uncoupled or unidirectionally coupled simulations. We expect
these enhancements to be generally applicable to other multiscale coupling
applications where timestepping occurs. In addition we have developed a "pressure
drop" residual which allows for stable coupling of flows between a 3D
incompressible CFD application and another (lower-dimensional) fluid system. We
expect this residual to also be useful for coupling non-respiratory
incompressible fluid applications, such as multiscale simulations involving blood
flow. The lower-dimensional models that are considered in this study are sets of
simple ordinary differential equations (ODEs) representing the compliant
mechanics of symmetric human pulmonary airway trees. To validate the method, we
compare the predictions of hybrid CFD-ODE models against an ODE-only model of
pulmonary airflow in an idealized geometry. Subsequently, we couple multiple sets
of ODEs describing the distal lung to an imaging-based human lung geometry.
Boundary conditions in these models consist of atmospheric pressure at the mouth
and intrapleural pressure applied to the multiple sets of ODEs. In both the
simplified geometry and in the imaging-based geometry, the performance of the
method was comparable to that of monolithic schemes, in most cases requiring only
a single CFD evaluation per time step. Thus, this new accelerator allows us to
begin combining pulmonary CFD models with lower-dimensional models of pulmonary
mechanics with little computational overhead. Moreover, because the CFD and lower
dimensional models are totally separate, this framework affords great flexibility
in terms of the type and breadth of the adopted lower-dimensional model, allowing
the biomedical researcher to appropriately focus on model design. Research funded
by the National Heart and Blood Institute Award 1RO1HL073598.
PMID- 24347682
TI - Gender Differences in Cognition among Older Adults in China.
AB - In this paper, we model gender differences in cognitive ability in China using a
new sample of middle-aged and older Chinese respondents. Modeled after the
American Health and Retirement Study (HRS), the CHARLS Pilot survey respondents
are 45 years and older in two quite distinct provinces-Zhejiang, a high-growth
industrialized province on the East Coast, and Gansu, a largely agricultural and
poor province in the West-in a sense new and old China. Our cognition measures
proxy for two different dimensions of adult cognition-episodic memory and intact
mental status. On both measures, Chinese women score much lower than do Chinese
men, a gender difference that grows among older Chinese cohorts. We relate both
these cognition scores to schooling, urban residence, family and community levels
of economic resources, and height. We find that cognition is more closely related
to mean community resources than to family resources, especially for women,
suggesting that in traditional poor Chinese communities there are strong economic
incentives to favor boys at the expense of girls. We also find that these gender
differences in cognitive ability have been steadily decreasing across birth
cohorts as the economy of China grew rapidly. Among cohorts of young adults in
China, there is no longer any gender disparity in cognitive ability. This
parallels the situation in the United States where cognition scores of adult
women actually exceed those of adult men.
PMID- 24347684
TI - Self-Healing of Unentangled Polymer Networks with Reversible Bonds.
AB - Self-healing polymeric materials are systems that after damage can revert to
their original state with full or partial recovery of mechanical strength. Using
scaling theory we study a simple model of autonomic self-healing of unentangled
polymer networks. In this model one of the two end monomers of each polymer chain
is fixed in space mimicking dangling chains attachment to a polymer network,
while the sticky monomer at the other end of each chain can form pairwise
reversible bond with the sticky end of another chain. We study the reaction
kinetics of reversible bonds in this simple model and analyze the different
stages in the self-repair process. The formation of bridges and the recovery of
the material strength across the fractured interface during the healing period
occur appreciably faster after shorter waiting time, during which the fractured
surfaces are kept apart. We observe the slowest formation of bridges for self
adhesion after bringing into contact two bare surfaces with equilibrium (very
low) density of open stickers in comparison with self-healing. The primary role
of anomalous diffusion in material self-repair for short waiting times is
established, while at long waiting times the recovery of bonds across fractured
interface is due to hopping diffusion of stickers between different bonded
partners. Acceleration in bridge formation for self-healing compared to self
adhesion is due to excess non-equilibrium concentration of open stickers. Full
recovery of reversible bonds across fractured interface (formation of bridges)
occurs after appreciably longer time than the equilibration time of the
concentration of reversible bonds in the bulk.
PMID- 24347683
TI - Repeated Cocaine Experience Facilitates Sucrose-Reinforced Operant Responding in
Enriched and Isolated Rats.
AB - The purpose of the present experiment was to determine whether repeated cocaine
exposure differentially affects sucrose-reinforced operant responding in rats
raised in an enriched condition (EC) or an isolated condition (IC). Specifically,
the performance of EC and IC rats pressing a lever for sucrose under a high fixed
ratio schedule (FR 30) prior to and after 10 days of exposure to cocaine (15
mg/kg, i.p.) or saline was compared. Regardless of rearing condition, rats
repeatedly exposed to cocaine had shorter reacquisition latencies to complete a
sucrose-reinforced FR 30 task than saline controls. The results suggest that
cocaine exposure may have cross-sensitized both EC and IC rats to the reinforcing
effects of sucrose or sucrose-associated cues, thus facilitating reacquisition of
operant responding.
PMID- 24347685
TI - Is DNA a Good Model Polymer?
AB - The details surrounding the cross-over from wormlike-specific to universal
polymeric behavior has been the subject of debate and confusion even for the
simple case of a dilute, unconfined wormlike chain. We have directly computed the
polymer size, form factor, free energy and Kirkwood diffusivity for unconfined
wormlike chains as a function of molecular weight, focusing on persistence
lengths and effective widths that represent single-stranded and double-stranded
DNA in a high ionic strength buffer. To do so, we use a chain-growth Monte Carlo
algorithm, the Pruned-Enriched Rosenbluth Method (PERM), which allows us to
estimate equilibrium and near-equilibrium dynamic properties of wormlike chains
over an extremely large range of contour lengths. From our calculations, we find
that very large DNA chains (~ 1,000,000 base pairs depending on the choice of
size metric) are required to reach flexible, swollen non-draining coils.
Furthermore, our results indicate that the commonly used model polymer lambda-DNA
(48,500 base pairs) does not exhibit "ideal" scaling, but exists in the middle of
the transition to long-chain behavior. We subsequently conclude that typical DNA
used in experiments are too short to serve as an accurate model of long-chain,
universal polymer behavior.
PMID- 24347686
TI - Architecture-Induced Size Asymmetry and Effective Interactions of Ring Polymers:
Simulation and Theory.
AB - We investigate, by means of Monte Carlo simulations, the role of ring
architecture and topology on the relative sizes of two interacting polymers as a
function of the distance between their centers-of-mass. As a general rule,
polymers swell as they approach each other, irrespectively of their topologies.
For each mutual separation, two identical linear polymers adopt the same average
size. However, unknotted rings at close separations adopt different sizes, with
the small one being "nested" within the large one over long time intervals,
exchanging their roles in the course of the simulation. For two rings of
different architectures and identical polymerization degree, the knotted one is
always smaller, penetrating the unknotted one. On the basis of these
observations, we propose a phenomenological theory for the effective interactions
between rings, modeling them as unequal-sized penetrable spheres. This simple
approximation provides a good description of the simulation results. In
particular, it rationalizes the non-Gaussian shape and the short-distance plateau
observed in the effective potential between unknotted ring polymers and pairs of
unequal-sized unknotted/knotted ones. Our results demonstrate the crucial role of
the architecture on both the effective interactions and the molecular size for
strongly interpenetrating polymers.
PMID- 24347689
TI - A Combined Multiple-SLED Broadband Light Source at 1300 nm for High Resolution
Optical Coherence Tomography.
AB - We demonstrate a compact, inexpensive, and reliable fiber-coupled light source
with broad bandwidth and sufficient power at 1300 nm for high resolution optical
coherence tomography (OCT) imaging in real-time applications. By combining four
superluminescent diodes (SLEDs) with different central wavelengths, the light
source has a bandwidth of 145 nm centered at 1325 nm with over 10 mW of power.
OCT images of an excised stage 30 embryonic chick heart acquired with our
combined SLED light source (<5 MUm axial resolution in tissue) are compared with
images obtained with a single SLED source (~10 MUm axial resolution in tissue).
The high resolution OCT system with the combined SLED light source provides
better image quality (smaller speckle noise) and a greater ability to observe
fine structures in the embryonic heart.
PMID- 24347690
TI - Of Elections and Emeritus Memberships.
PMID- 24347691
TI - Enhanced Religiosity Following Illness? Assessing Evidence of Religious
Consolation Among Black and White Americans.
AB - This study assesses variation among Black and White Americans in the impact of
ill-health on public and subjective religiosity. It is the first longitudinal
assessment of race-based variation in "religious consolation." The under-explored
consolation thesis anticipates ill-health influencing religiosity rather than the
reverse, with religiosity functioning as a coping resource marshaled by the ill.
Effects across races of physical ill-health indicators (chronic illnesses and
impaired functioning) on religiosity outcomes are the main focus; but across-race
variation in psychological distress-induced "consolation" is also assessed.
Findings yield only limited evidence of consolation in each race, and restricted
variation across races: Change in impaired functioning slightly enhances Whites'
subjective religiosity; but that effect does not significantly eclipse the impact
among Blacks. There is no evidence of physical illness-induced consolation among
Blacks; and the proposition that Blacks are more inclined toward consolation than
Whites is affirmed only for psychological distress. There are no signs in either
race that consolation is intensified by aging or higher religiosity, and no
significant across-race differentials in effects of these illness-age and illness
religiosity interactions on subsequent religiosity. The multi-population model
utilizes Americans' Changing Lives data.
PMID- 24347692
TI - CmlI is an N-oxygenase in the biosynthesis of chloramphenicol.
AB - The N-oxygenation of an amine group is one of the steps in the biosynthesis of
the antibiotic chloramphenicol. The non-heme di-iron enzyme CmlI was identified
as the enzyme catalyzing this reaction through bioinformatics studies and
reconstitution of enzymatic activity. In vitro reconstitution was achieved using
phenazine methosulfate and NADH as electron mediators, while in vivo activity was
demonstrated in Escherichia coli using two substrates. Kinetic analysis showed a
biphasic behavior of the enzyme. Oxidized hydroxylamine and nitroso compounds in
the reaction were detected both in vitro and in vivo based on LC-MS. The active
site metal was confirmed to be iron based on a ferrozine assay. These findings
provide new insights into the biosynthesis of chloramphenicol and could lead to
further development of CmlI as a useful biocatalyst.
PMID- 24347693
TI - (1-bromovinyl)-MIDA boronate: a readily accessible and highly versatile building
block for small molecule synthesis.
PMID- 24347694
TI - Iterative Reducible Ligation to form Homogeneous Penicillamine Cross-linked
Polypeptides.
AB - The syntheses of homogeneous penicillamine disulfide cross-linked polypeptides
are reported. Dodecapeptides containing N-terminal, C-terminal, or N- and C
terminal Pen were serially ligated into 36 amino acid polypeptides linked through
Cys-Pen, Pen-Cys or Pen-Pen disulfide bonds. Critical to the syntheses was the
incorporation of thiazolidine masked Cys and Pen as the N-terminal residues and
selective hydrolysis with silver trifluoromethanesulfonate in acidic aqueous
conditions to generate a free thiol for subsequent ligation. This approach allows
the synthesis of homogeneous disulfide cross-linked polypeptides that have
different reductive stabilities and have application in gene delivery by
undergoing a tempered reductive triggered release of DNA.
PMID- 24347695
TI - Three-step synthesis of an annulated beta-carboline via palladium catalysis.
AB - The synthesis of beta-carbolines is a mature field, yet new methods are desirable
to introduce new functionality onto the core scaffold. We describe the
incorporation of an additional fused ring onto the beta-carboline via a novel
palladium-catalyzed, one-pot Sonogashira coupling/intramolecular [2+2+2]
cyclization. This method generates three rings in one flask and produces an
annulated beta-carboline in 80% yield. A preliminary mechanistic study into the
sequence of events is described, which confirms an unprecedented catalytic role
for palladium.
PMID- 24347697
TI - Human resources for universal health coverage: from evidence to policy and
action.
PMID- 24347698
TI - Investing in human resources for health: the need for a paradigm shift.
PMID- 24347700
TI - Beyond clinical skills: key capacities needed for universal health coverage.
PMID- 24347699
TI - Human resources for universal health coverage: leadership needed.
PMID- 24347702
TI - More midwives needed to improve maternal and newborn survival.
AB - Retention of midwives, especially in rural areas, is a major challenge for many
countries, one that threatens to negate all the hard work and resources invested
in their training. Priya Shetty reports.
PMID- 24347703
TI - Funding, flexible management needed for Brazil's health worker gaps. Interview by
Claudia Jurberg.
AB - Last month the first Cuban physicians arrived in Brazil under a new government
programme to work in underserved parts of the country, both rural and urban.
Francisco Eduardo de Campos tells Claudia Jurberg why the Mais Medicos (More
Physicians) programme is necessary.
PMID- 24347704
TI - Health worker remuneration in WHO Member States.
AB - OBJECTIVE: To present the available data on the money spent by Member States of
the World Health Organization (WHO) on remunerating health workers in the public
and private sectors. METHODS: Data on government and total expenditure on health
worker remuneration were obtained through a review of official documents in WHO's
Global Health Expenditure Database and directly from country officials and
country official web sites. Such data are presented in this paper, by World Bank
country income groups, in millions of national currency units per calendar year
for salaried and non-salaried health workers. They are presented as a share of
gross domestic product (GDP), total health expenditure and general government
health expenditure. The average yearly change in remuneration (i.e. compound
annual growth rate) between 2000 and 2012 as a function of these parameters was
also assessed. FINDINGS: On average, payments to health workers of all types
accounted for more than one third of total health expenditure across countries.
Such payments have grown faster than countries' GDPs but less rapidly than total
health expenditure and general government health expenditure. Remuneration of
health workers, on the other hand, has grown faster than that of other types of
workers. CONCLUSION: As they seek to attain universal health coverage (UHC),
countries will need to devote an increasing proportion of their GDPs to health
and health worker remuneration. However, the fraction of total health expenditure
devoted to paying health workers seems to be declining, partly because the
pursuit of UHC calls for strengthening the health system as a whole.
PMID- 24347705
TI - Monitoring the implementation of the WHO Global Code of Practice on the
International Recruitment of Health Personnel.
AB - OBJECTIVE: To present the findings of the first round of monitoring of the global
implementation of the WHO Global Code of Practice on the International
Recruitment of Health Personnel ("the Code"), a voluntary code adopted in 2010 by
all 193 Member States of the World Health Organization (WHO). METHODS: WHO
requested that its Member States designate a national authority for facilitating
information exchange on health personnel migration and the implementation of the
Code. Each designated authority was then sent a cross-sectional survey with 15
questions on a range of topics pertaining to the 10 articles included in the
Code. FINDINGS: A national authority was designated by 85 countries. Only 56
countries reported on the status of Code implementation. Of these, 37 had taken
steps towards implementing the Code, primarily by engaging relevant stakeholders.
In 90% of countries, migrant health professionals reportedly enjoy the same legal
rights and responsibilities as domestically trained health personnel. In the
context of the Code, cooperation in the area of health workforce development goes
beyond migration-related issues. An international comparative information base on
health workforce mobility is needed but can only be developed through a
collaborative, multi-partnered approach. CONCLUSION: Reporting on the
implementation of the Code has been suboptimal in all but one WHO region. Greater
collaboration among state and non-state actors is needed to raise awareness of
the Code and reinforce its relevance as a potent framework for policy dialogue on
ways to address the health workforce crisis.
PMID- 24347706
TI - Quality of care provided by mid-level health workers: systematic review and meta
analysis.
AB - OBJECTIVE: To assess the effectiveness of care provided by mid-level health
workers. METHODS: Experimental and observational studies comparing mid-level
health workers and higher level health workers were identified by a systematic
review of the scientific literature. The quality of the evidence was assessed
using Grading of Recommendations Assessment, Development and Evaluation criteria
and data were analysed using Review Manager. FINDINGS: Fifty-three studies,
mostly from high-income countries and conducted at tertiary care facilities, were
identified. In general, there was no difference between the effectiveness of care
provided by mid-level health workers in the areas of maternal and child health
and communicable and noncommunicable diseases and that provided by higher level
health workers. However, the rates of episiotomy and analgesia use were
significantly lower in women giving birth who received care from midwives alone
than in those who received care from doctors working in teams with midwives, and
women were significantly more satisfied with care from midwives. Overall, the
quality of the evidence was low or very low. The search also identified six
observational studies, all from Africa, that compared care from clinical
officers, surgical technicians or non-physician clinicians with care from
doctors. Outcomes were generally similar. CONCLUSION: No difference between the
effectiveness of care provided by mid-level health workers and that provided by
higher level health workers was found. However, the quality of the evidence was
low. There is a need for studies with a high methodological quality, particularly
in Africa - the region with the greatest shortage of health workers.
PMID- 24347707
TI - Early implementation of WHO recommendations for the retention of health workers
in remote and rural areas.
AB - The maldistribution of health workers between urban and rural areas is a policy
concern in virtually all countries. It prevents equitable access to health
services, can contribute to increased health-care costs and underutilization of
health professional skills in urban areas, and is a barrier to universal health
coverage. To address this long-standing concern, the World Health Organization
(WHO) has issued global recommendations to improve the rural recruitment and
retention of the health workforce. This paper presents experiences with local and
regional adaptation and adoption of WHO recommendations. It highlights challenges
and lessons learnt in implementation in two countries - the Lao People's
Democratic Republic and South Africa - and provides a broader perspective in two
regions - Asia and Europe. At country level, the use of the recommendations
facilitated a more structured and focused policy dialogue, which resulted in the
development and adoption of more relevant and evidence-based policies. At
regional level, the recommendations sparked a more sustained effort for cross
country policy assessment and joint learning. There is a need for impact
assessment and evaluation that focus on the links between the rural availability
of health workers and universal health coverage. The effects of any health
financing reforms on incentive structures for health workers will also have to be
assessed if the central role of more equitably distributed health workers in
achieving universal health coverage is to be supported.
PMID- 24347708
TI - Why do health labour market forces matter?
AB - Human resources for health have been recognized as essential to the development
of responsive and effective health systems. Low- and middle-income countries
seeking to achieve universal health coverage face human resource constraints -
whether in the form of health worker shortages, maldistribution of workers or
poor worker performance - that seriously undermine their ability to achieve well
functioning health systems. Although much has been written about the human
resource crisis in the health sector, labour economic frameworks have seldom been
applied to analyse the situation and little is known or understood about the
operation of labour markets in low- and middle-income countries. Traditional
approaches to addressing human resource constraints have focused on workforce
planning: estimating health workforce requirements based on a country's
epidemiological and demographic profile and scaling up education and training
capacities to narrow the gap between the "needed" number of health workers and
the existing number. However, this approach neglects other important factors that
influence human resource capacity, including labour market dynamics and the
behavioural responses and preferences of the health workers themselves. This
paper describes how labour market analysis can contribute to a better
understanding of the factors behind human resource constraints in the health
sector and to a more effective design of policies and interventions to address
them. The premise is that a better understanding of the impact of health policies
on health labour markets, and subsequently on the employment conditions of health
workers, would be helpful in identifying an effective strategy towards the
progressive attainment of universal health coverage.
PMID- 24347709
TI - Community health workers for universal health-care coverage: from fragmentation
to synergy.
AB - To achieve universal health coverage, health systems will have to reach into
every community, including the poorest and hardest to access. Since Alma-Ata,
inconsistent support of community health workers (CHWs) and failure to integrate
them into the health system have impeded full realization of their potential
contribution in the context of primary health care. Scaling up and maintaining
CHW programmes is fraught with a host of challenges: poor planning; multiple
competing actors with little coordination; fragmented, disease-specific training;
donor-driven management and funding; tenuous linkage with the health system; poor
coordination, supervision and support, and under-recognition of CHWs'
contribution. The current drive towards universal health coverage (UHC) presents
an opportunity to enhance people's access to health services and their trust,
demand and use of such services through CHWs. For their potential to be fully
realized, however, CHWs will need to be better integrated into national health
care systems in terms of employment, supervision, support and career development.
Partners at the global, national and district levels will have to harmonize and
synchronize their engagement in CHW support while maintaining enough flexibility
for programmes to innovate and respond to local needs. Strong leadership from the
public sector will be needed to facilitate alignment with national policy
frameworks and country-led coordination and to achieve synergies and
accountability, universal coverage and sustainability. In moving towards UHC,
much can be gained by investing in building CHWs' skills and supporting them as
valued members of the health team. Stand-alone investments in CHWs are no
shortcut to progress.
PMID- 24347710
TI - Human resources for health and universal health coverage: fostering equity and
effective coverage.
AB - Achieving universal health coverage (UHC) involves distributing resources,
especially human resources for health (HRH), to match population needs. This
paper explores the policy lessons on HRH from four countries that have achieved
sustained improvements in UHC: Brazil, Ghana, Mexico and Thailand. Its purpose is
to inform global policy and financial commitments on HRH in support of UHC. The
paper reports on country experiences using an analytical framework that examines
effective coverage in relation to the availability, accessibility, acceptability
and quality (AAAQ) of HRH. The AAAQ dimensions make it possible to perform
tracing analysis on HRH policy actions since 1990 in the four countries of
interest in relation to national trends in workforce numbers and population
mortality rates. The findings inform key principles for evidence-based decision
making on HRH in support of UHC. First, HRH are critical to the expansion of
health service coverage and the package of benefits; second, HRH strategies in
each of the AAAQ dimensions collectively support achievements in effective
coverage; and third, success is achieved through partnerships involving health
and non-health actors. Facing the unprecedented health and development challenges
that affect all countries and transforming HRH evidence into policy and practice
must be at the heart of UHC and the post-2015 development agenda. It is a
political imperative requiring national commitment and leadership to maximize the
impact of available financial and human resources, and improve healthy life
expectancy, with the recognition that improvements in health care are enabled by
a health workforce that is fit for purpose.
PMID- 24347711
TI - Strengthening human resources for health through multisectoral approaches and
leadership: the case of Cameroon.
AB - PROBLEM: Cameroon has a severe shortage of human resources for health (HRH) and
those that are available are concentrated in urban areas. APPROACH: As the result
of a national emergency plan for the years 2006-2008, innovative strategies and a
multisectoral partnership - led by the Ministry of Public Health and supported by
diverse national and international organizations - were developed to address the
shortages and maldistribution of HRH in Cameroon. LOCAL SETTING: At the time that
the emergency plan was developed, Cameroon had health services of poor quality,
an imbalance between HRH training and employment, a maldistribution of HRH
between urban and rural areas and a poor allocation of financial resources for
HRH. It also lacked an accreditation system for use in the training of health
workers. RELEVANT CHANGES: Between 2007 and 2009, the number of active health
workers in Cameroon increased by 36%, several new institutions for higher
education in health care and training schools for paramedical staff and midwives
were opened, and a national strategy for universal health coverage was developed.
LESSONS LEARNT: In the improvement of HRH, strong leadership is needed to ensure
effective coordination and communication between the many different stakeholders.
A national process of coordination and facilitation can produce a consensus-based
view of the main HRH challenges. Once these challenges have been identified, the
stakeholders can plan appropriate interventions that are coordinated, evidence
based and coherent.
PMID- 24347712
TI - Strengthening human resources for health through information, coordination and
accountability mechanisms: the case of the Sudan.
AB - PROBLEM: Human resources for health (HRH) in the Sudan were limited by shortages
and the maldistribution of health workers, poor management, service
fragmentation, poor retention of health workers in rural areas, and a weak health
information system. APPROACH: A "country coordination and facilitation" process
was implemented to strengthen the national HRH observatory, provide a
coordination platform for key stakeholders, catalyse policy support and HRH
planning, harmonize the mobilization of resources, strengthen HRH managerial
structures, establish new training institutions and scale up the training of
community health workers. LOCAL SETTING: The national government of the Sudan
sanctioned state-level governance of the health system but many states lacked
coherent HRH plans and policies. A paucity of training institutions constrained
HRH production and the adequate and equitable deployment of health workers in
rural areas. RELEVANT CHANGES: The country coordination and facilitation process
prompted the establishment of a robust HRH information system and the development
of the technical capacities and tools necessary for data analysis and evidence
based participatory decision-making and action. LESSONS LEARNT: The success of
the country coordination and facilitation process was substantiated by the
stakeholders' coordinated support, which was built on solid evidence of the
challenges in HRH and shared accountability in the planning and implementation of
responses to those challenges. The support led to political commitment and the
mobilization of resources for HRH. The leadership that was promoted and the
educational institutions that were opened should facilitate the training,
deployment and retention of the health workers needed to achieve universal health
coverage.
PMID- 24347713
TI - Health workforce contributions to health system development: a platform for
universal health coverage.
AB - PROBLEM: In the 1970s, Thailand was a low-income country with poor health
indicators and low health service coverage. The local health infrastructure was
especially weak. APPROACH: In the 1980s, measures were initiated to reduce
geographical barriers to health service access, improve the health infrastructure
at the district level, make essential medicines more widely available and develop
a competent, committed health workforce willing to service rural areas. To ensure
service accessibility, financial risk protection schemes were expanded. LOCAL
SETTING: In Thailand, district hospitals were practically non-existent in the
1960s. Expansion of primary health care (PHC), especially in poor rural areas,
was considered essential for attaining universal health coverage (UHC).
Nationwide reforms led to important changes in a few decades. RELEVANT CHANGES:
Over the past 30 years, the availability and distribution of health workers, as
well as their skills and competencies, have greatly improved, along with national
health indicators. Between 1980 and 2000 coverage with maternal and child health
services increased substantially. By 2002, Thailand had attained UHC. Overall
health system development, particularly an expanded health workforce, resulted in
a functioning PHC system. LESSONS LEARNT: A competent, committed health workforce
helped strengthen the PHC system at the district level. Keeping the policy focus
on the development of human resources for health (HRH) for an extended period was
essential, together with a holistic approach to the development of HRH,
characterized by the integration of different kinds of HRH interventions and the
linking of these interventions with broader efforts to strengthen other health
system domains.
PMID- 24347715
TI - Health workforce indicators: let's get real.
PMID- 24347714
TI - Tackling health workforce challenges to universal health coverage: setting
targets and measuring progress.
AB - Human resources for health (HRH) will have to be strengthened if universal health
coverage (UHC) is to be achieved. Existing health workforce benchmarks focus
exclusively on the density of physicians, nurses and midwives and were developed
with the objective of attaining relatively high coverage of skilled birth
attendance and other essential health services of relevance to the health
Millennium Development Goals (MDGs). However, the attainment of UHC will depend
not only on the availability of adequate numbers of health workers, but also on
the distribution, quality and performance of the available health workforce. In
addition, as noncommunicable diseases grow in relative importance, the inputs
required from health workers are changing. New, broader health-workforce
benchmarks - and a corresponding monitoring framework - therefore need to be
developed and included in the agenda for UHC to catalyse attention and investment
in this critical area of health systems. The new benchmarks need to reflect the
more diverse composition of the health workforce and the participation of
community health workers and mid-level health workers, and they must capture the
multifaceted nature and complexities of HRH development, including equity in
accessibility, sex composition and quality.
PMID- 24347716
TI - Towards universal health coverage: a health workforce fit for purpose and
practice.
PMID- 24347717
TI - Health workforce benchmarks for universal health coverage and sustainable
development.
PMID- 24347718
TI - Empowering patients and strengthening communities for real health workforce and
funding targets.
PMID- 24347719
TI - Leveraging information technology to bridge the health workforce gap.
PMID- 24347720
TI - A comprehensive health labour market framework for universal health coverage.
PMID- 24347721
TI - Can human resources for health in the context of noncommunicable disease control
be a lever for health system changes?
PMID- 24347725
TI - Public health management of mass gatherings: the Saudi Arabian experience with
MERS-CoV.
PMID- 24347724
TI - Knowledge is power; information is liberation.
PMID- 24347727
TI - Push for palliative care stokes debate.
AB - With the ageing of populations and a heavy burden of noncommunicable diseases
around the world, there is a high but unmet demand for palliative care in many
countries. Gary Humphreys reports.
PMID- 24347728
TI - The joy of facts and figures by Fiona Fleck.
AB - Hans Rosling tells Fiona Fleck why it's easy to make health statistics
interesting but difficult to persuade people to accept a fact-based view of the
world.
PMID- 24347729
TI - Frequent exposure to suboptimal temperatures in vaccine cold-chain system in
India: results of temperature monitoring in 10 states.
AB - OBJECTIVE: To estimate the proportion of time the vaccines in the cold-chain
system in India are exposed to temperatures of < 0 or > 8 degrees C. METHODS: In
each of 10 states, the largest district and the one most distant from the state
capital were selected for study. Four boxes, each containing an electronic
temperature recorder and two vials of diphtheria, pertussis and tetanus vaccine,
were placed in the state or regional vaccine store for each study state. Two of
these boxes were then shipped - one per facility - towards the two most
peripheral health facilities where vaccine was stored in each study district. The
boxes were shipped, handled and stored as if they were routine vaccine supplies.
FINDINGS: In state, regional and district vaccine stores and peripheral health
facilities, respectively, the temperatures in the boxes exceeded 8 degrees C for
14.3%, 13.2%, 8.3% and 14.7% of their combined storage times and fell below 0
degrees C for 1.5%, 0.2%, 0.6% and 10.5% of these times. The boxes also spent
about 18% and 7% of their combined times in transit at < 0 and > 8 degrees C,
respectively. In shake tests conducted at the end of the study, two thirds of the
vaccine vials in the boxes showed evidence of freezing. CONCLUSION: While
exposure to temperatures above 8 degrees C occurred at every level of vaccine
storage, exposure to subzero temperatures was only frequent during vaccine
storage at peripheral facilities and vaccine transportation. Systematic efforts
are needed to improve temperature monitoring in the cold-chain system in India.
PMID- 24347730
TI - Trends in caesarean delivery by country and wealth quintile: cross-sectional
surveys in southern Asia and sub-Saharan Africa.
AB - OBJECTIVE: To examine temporal trends in caesarean delivery rates in southern
Asia and sub-Saharan Africa, by country and wealth quintile. METHODS: Cross
sectional data were extracted from the results of 80 Demographic and Health
Surveys conducted in 26 countries in southern Asia or sub-Saharan Africa.
Caesarean delivery rates were evaluated - as percentages of the deliveries that
ended in live births - for each wealth quintile in each survey. The annual rates
recorded for each country were then compared to see if they had increased over
time. FINDINGS: Caesarean delivery rates had risen over time in all but 6 study
countries but were consistently found to be lower than 5% in 18 of the countries
and 10% or less in the other eight countries. Among the poorest 20% of the
population, caesarean sections accounted for less than 1% and less than 2% of
deliveries in 12 and 21 of the study countries, respectively. In each of 11
countries, the caesarean delivery rate in the poorest 40% of the population
remained under 1%. In Chad, Ethiopia, Guinea, Madagascar, Mali, Mozambique, Niger
and Nigeria, the rate remained under 1% in the poorest 80%. Compared with the 22
African study countries, the four study countries in southern Asia experienced a
much greater rise in their caesarean delivery rates over time. However, the rates
recorded among the poorest quintile in each of these countries consistently fell
below 2%. CONCLUSION: Caesarean delivery rates among large sections of the
population in sub-Saharan Africa are very low, probably because of poor access to
such surgery.
PMID- 24347731
TI - Monitoring service delivery for universal health coverage: the Service
Availability and Readiness Assessment.
AB - OBJECTIVE: To describe the Service Availability and Readiness Assessment (SARA)
and the results of its implementation in six countries across three continents.
METHODS: The SARA is a comprehensive approach for assessing and monitoring health
service availability and the readiness of facilities to deliver health-care
interventions, with a standardized set of indicators that cover all main
programmes. Standardized data-collection instruments are used to gather
information on a defined set of selected tracer items from public and private
health facilities through a facility sample survey or census. Results from
assessments in six countries are shown. FINDINGS: The results highlight important
gaps in service delivery that are obstacles to universal access to health
services. Considerable variation was found within and across countries in the
distribution of health facility infrastructure and workforce and in the types of
services offered. Weaknesses in laboratory diagnostic capacities and gaps in
essential medicines and commodities were common across all countries. CONCLUSION:
The SARA fills an important information gap in monitoring health system
performance and universal health coverage by providing objective and regular
information on all major health programmes that feeds into country planning
cycles.
PMID- 24347732
TI - Management of children exposed to Mycobacterium tuberculosis: a public health
evaluation in West Java, Indonesia.
AB - OBJECTIVE: To investigate qualitatively and quantitatively the performance of a
programme for managing the child contacts of adult tuberculosis patients in
Indonesia. METHODS: A public health evaluation framework was used to assess gaps
in a child contact management programme at a lung clinic. Targets for programme
performance indicators were derived from established programme indicator targets,
the scientific literature and expert opinion. Compliance with tuberculosis
screening, the initiation of isoniazid preventive therapy in children younger
than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive
therapy were assessed in 755 child contacts in two cohorts. In addition, 22
primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and
acceptance of child contact management. The cost to caregivers was recorded. Gaps
between observed and target indicator values were quantified. FINDINGS: THE GAPS
BETWEEN OBSERVED AND TARGET PERFORMANCE INDICATORS WERE: 82% for screening
compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of
preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff
did not have adequate knowledge of, or an appropriate attitude towards, child
contact management, especially regarding isoniazid preventive therapy. Caregivers
had good knowledge of screening but not of preventive therapy and had difficulty
travelling to the clinic and paying costs. CONCLUSION: The study identified
widespread gaps in the performance of a child contact management system in
Indonesia, all of which appear amenable to intervention. The public health
evaluation framework used could be applied in other settings where child contact
management is failing.
PMID- 24347733
TI - The impact of rural health system reform on hospitalization rates in the Islamic
Republic of Iran: an interrupted time series.
AB - OBJECTIVE: To assess the effects on hospital utilization rates of a major health
system reform - a family physician programme and a social protection scheme -
undertaken in rural areas of the Islamic Republic of Iran in 2005. METHODS: A
"tracer" province that was not a patient referral hub was selected for the
collection of monthly hospitalization data over a period of about 10 years,
beginning two years before the rural health system reform (the "intervention")
began. An interrupted time series analysis was conducted and segmented regression
analysis was used to assess the immediate and gradual effects of the intervention
on hospitalization rates in an intervention group composed of rural residents and
a comparison group composed of urban residents primarily. FINDINGS: Before the
intervention, the hospitalization rate in the rural population was significantly
lower than in the comparison group. Although there was no significant increase or
decline in hospitalization rates in the intervention or comparison group before
the intervention, after the intervention a significant increase in the
hospitalization rate - of 4.6 hospitalizations per 100 000 insured persons per
month on average - was noted in the intervention group (P < 0.001). The monthly
increase in the hospitalization rate continued for over a year and stabilized
thereafter. No increase in the hospitalization rate was observed in the
comparison group. CONCLUSION: The primary health-care programme instituted as
part of the health system reform process has increased access to hospital care in
a population that formerly underutilized hospital services. It has not reduced
hospitalizations or hospitalization-related expenditure.
PMID- 24347734
TI - The ethics of feedback of HIV test results in population-based surveys of HIV
infection.
AB - Population-based disease prevalence surveys raise ethical questions, including
whether participants should be routinely told their test results. Ethical
guidelines call for informing survey participants of any clinically relevant
finding to enable appropriate management. However, in anonymous surveys of human
immunodeficiency virus (HIV) infection, participants can "opt out" of being given
their test results or are offered the chance to undergo voluntary HIV testing in
local counselling and testing services. This is aimed at minimizing survey
participation bias. Those who opt out of being given their HIV test results and
who do not seek their results miss the opportunity to receive life-saving
antiretroviral therapy. The justification for HIV surveys without routine
feedback of results to participants is based on a public health utility argument:
that the benefits of more rigorous survey methods - reduced participation bias -
outweigh the benefits to individuals of knowing their HIV status. However, people
with HIV infection have a strong immediate interest in knowing their HIV status.
In consideration of the ethical value of showing respect for people and thereby
alleviating suffering, an argument based on public health utility is not an
appropriate justification. In anonymous HIV surveys as well as other prevalence
surveys of treatable conditions in any setting, participation should be on the
basis of routine individual feedback of results as an integral part of fully
informed participation. Ensuring that surveys are ethically sound may stimulate
participation, increase a broader uptake of HIV testing and reduce stigmatization
of people who are HIV-positive.
PMID- 24347735
TI - Rapid monitoring in vaccination campaigns during emergencies: the post-earthquake
campaign in Haiti.
AB - PROBLEM: The earthquake that struck Haiti in January 2010 caused 1.5 million
people to be displaced to temporary camps. The Haitian Ministry of Public Health
and Population and global immunization partners developed a plan to deliver
vaccines to those residing in these camps. A strategy was needed to determine
whether the immunization targets set for the campaign were achieved. APPROACH:
Following the vaccination campaign, staff from the Ministry of Public Health and
Population interviewed convenience samples of households - in specific
predetermined locations in each of the camps - regarding receipt of the emergency
vaccinations. A camp was targeted for "mop-up vaccination" - i.e. repeat mass
vaccination - if more than 25% of the children aged 9 months to 7 years in the
sample were found not to have received the emergency vaccinations. LOCAL SETTING:
Rapid monitoring was implemented in camps located in the Port-au-Prince
metropolitan area. Camps that housed more than 5000 people were monitored first.
RELEVANT CHANGES: By the end of March 2010, 72 (23%) of the 310 vaccinated camps
had been monitored. Although 32 (44%) of the monitored camps were targeted for
mop-up vaccination, only six of them had received such repeat mass vaccination
when checked several weeks after monitoring. LESSONS LEARNT: Rapid monitoring was
only marginally beneficial in achieving immunization targets in the temporary
camps in Port-au-Prince. More research is needed to evaluate the utility of
conventional rapid monitoring, as well as other strategies, during post-disaster
vaccination campaigns that involve mobile populations, particularly when there is
little capacity to conduct repeat mass vaccination.
PMID- 24347736
TI - Local production of WHO-recommended alcohol-based handrubs: feasibility,
advantages, barriers and costs.
AB - PROBLEM: Reduction of health-care-associated infections in low- and middle-income
countries is hampered by inadequate supplies of soap and water and the lack or
high cost of alcohol-based handrubs (ABHs). APPROACH: In 2005, the World Health
Organization (WHO) developed and tested two formulations for ABHs that were
suitable for production in health-care facilities. In 2011, the feasibility,
advantages and costs of the local production of the two formulations - and the
barriers to such production - were evaluated in an online survey. LOCAL SETTING:
The survey included 34 health-care facilities and 5 private companies in 29
countries. RELEVANT CHANGES: Local production of one of the WHO formulations was
feasible in every participating site. Twenty-one (54%) of the sites had replaced
a previously used ABH with one of the WHO formulations. In 32 sites, the WHO
formulation that had been produced was well tolerated and accepted by health-care
workers. The WHO formulations were found to be less expensive than marketed ABHs.
Barriers to local production included difficulty in identifying staff with
adequate skills, the need for staff training, and constraints in ingredient and
dispenser procurement. LESSONS LEARNT: The WHO formulations can be easily
produced locally at low cost. They are well tolerated and accepted by health-care
workers. Potential barriers to their local production - such as their smell and
problems in the procurement of ingredients and dispensers and in performing
quality control - require further investigation.
PMID- 24347737
TI - Aggression and Rule-breaking: Heritability and stability of antisocial behavior
problems in childhood and adolescence.
AB - PURPOSE: This twin study examined the structure of genetic and environmental
influences on aggression and rule-breaking in order to examine change and
stability across the span of childhood to mid-adolescence. METHODS: Behavioral
assessments were conducted at two time points: age 9-10 years and 14-15 years.
Using behavioral genetics biometric modeling, the longitudinal structure of
influences was investigated. RESULTS: Aggression and rule-breaking were found to
be influenced by a latent common factor of antisocial behavior (ASB) within each
wave of data collection. The childhood-age common factor of ASB was influenced by
41% genetics, 40% shared environment and 19% nonshared environment. In
adolescence, 41% of influences on the common factor were novel and entirely
genetic, while the remainder of influences were stable across time. Additionally,
both aggression and rule-breaking within each wave were found to have unique
influences not common across subscales or across waves, highlighting specificity
of influences on different problem behaviors at both ages. CONCLUSIONS: This
research sheds light on the commonality of influences on etiology of different
forms of antisocial behavior, and suggests future directions for research into
intervention for antisocial behavior problems in youth, such as investigation of
adolescence-specific environmental influences on the development of antisocial
behavior problems.
PMID- 24347738
TI - What Causes BDD: Research Findings and a Proposed Model.
PMID- 24347739
TI - Optimism and Resources: Effects on Each Other and on Health over 10 Years.
AB - Dispositional optimism may be associated with growth of social and status
resources by virtue of optimists' greater persistence and better performance.
Conversely, resource growth may give people a more positive view of their future
and increase optimism. Changes in dispositional optimism and resources over 10
years were examined in former law students (N = 61). More optimistic first-year
law students made more money 10 years later, but income did not predict later
optimism. More optimistic students did not have larger social networks 10 years
later, but increases in social network size predicted increased optimism. These
changes predicted mental and physical health. Dispositional optimism was less
stable than many personality traits (r = .35), potentially because it is
responsive to resource change.
PMID- 24347740
TI - Disentangling leaf area and environmental effects on the response of the net
ecosystem CO2 exchange to diffuse radiation.
AB - There is an ongoing discussion about why the net ecosystem CO2 exchange (NEE) of
some ecosystems is less sensitive to diffuse radiation than others and about the
role other environmental factors play in determining the response of NEE to
diffuse radiation. Using a six-year data set from a temperate mountain grassland
in Austria we show that differences between ecosystems may be reconciled based on
their green area index (GAI; square meter green plant area per square meter
ground area) - the sensitivity to diffuse radiation increasing with GAI. Our data
suggest diffuse radiation to have a negligible influence on NEE below a GAI of 2
m2 m-2. Changes in air/soil temperature and air humidity concurrent with the
fraction of diffuse radiation were found to amplify the sensitivity of the
investigated temperate mountain grassland ecosystem to diffuse radiation.
PMID- 24347741
TI - The Experience of Discrimination and Black-White Health Disparities in Medical
Care.
AB - The current study of Black patients focuses on how discrimination contributes to
racial disparities in health. The authors used a longitudinal methodology to
study how perceived past discrimination affects reactions to medical interactions
and adherence to physician recommendations. In addition, they explored whether
these reactions and/or adherence mediate the relationship between discrimination
and patients' health. The participants in this study were 156 Black patients of
low socioeconomic status at a primary care clinic. Patients completed
questionnaires on their current health, past adherence, and perceived past
discrimination. Then, they saw a physician and rated their reactions to the
visit. Four and 16 weeks later they reported on their adherence to physician
recommendations and overall health. Perceived discrimination was significantly
and negatively associated with patient health, reactions to the physician, and
adherence. Path analyses indicated that adherence mediated the relationship
between discrimination and patient health, but patient reactions to the
interaction did not.
PMID- 24347742
TI - Ionization effects in molecular depth profiling of trehalose films using
buckminsterfullerene (C60) cluster ions.
AB - Salts play a mysterious role in desorption mass spectrometry, especially in
biological samples.[1] We used trehalose films doped with a peptide as a well
defined model system to investigate the ionization effects in organic molecular
depth profiling. Sodium salts at 1% level were added into the solution used to
produce the trehalose films, and depth profiles were obtained with a C60 ion
source. The results show that the protonated molecular ion signal from the
peptide and the quasimolecular ion signal of trehalose are significantly
suppressed by the addition of salts, whereas the signals representing salt
clusters and salt adducts of trehalose are formed in both positive and negative
modes. The formation of protonated molecular ions is found to correlate with the
ratio between protonated and bare water ions, suggesting that the latter can be
used as an indicator for the accumulation of protons liberated by the ion
bombardment. In experiments where no salt was added, it is shown that the surface
variation of the protonated molecular ion signal strongly depends upon the water
content of the trehalose film.
PMID- 24347743
TI - Fundamental studies of molecular depth profiling using organic delta layers as
model systems.
AB - Alternating Langmuir-Blodgett multilayers of barium arachidate (AA) and barium
dimyristoyl phosphatidate (DMPA) were used to elucidate the factors that control
depth resolution in molecular depth profiling experiments. More specifically,
thin (4.4 nm) layers of DMPA were embedded in relatively thick (~50 nm)
multilayer stacks of AA, resulting in a well-defined delta-layer model system
closely resembling a biological membrane. This system was subjected to a three
dimensional imaging depth profile analysis using a focused buckminsterfullerene
(C60) cluster ion beam. The depth response function measured in these experiments
exhibits similar features as those determined in inorganic depth profiling:
namely, an asymmetric shape with quasi-exponential leading and trailing edges and
a central Gaussian peak. The magnitude of the corresponding characteristic rise
and decay lengths is found to be 5 and 16 nm, respectively, while the total half
width of the response function characterizing the apparent depth resolution was
about 29 nm. Ion-induced mixing is proposed to be largely responsible for the
broadening, rather than topography, as determined by atomic force microscopy.
PMID- 24347744
TI - Retrospective sputter depth profiling using 3D mass spectral imaging.
AB - A molecular multilayer stack composed of alternating Langmuir-Blodgett films was
analyzed by ToF-SIMS imaging in combination with intermediate sputter erosion
using a focused C60+ cluster ion beam. From the resulting dataset, depth profiles
of any desired lateral portion of the analyzed field-of-view can be extracted in
retrospect, allowing the influence of the gating area on the apparent depth
resolution to be assessed. In a similar way, the observed degradation of depth
resolution with increasing depth of the analyzed interface can be analyzed in
order to determine the 'intrinsic' depth resolution of the method.
PMID- 24347745
TI - Temperature effects in the sputtering of a molecular solid by energetic atomic
and cluster projectiles.
AB - Temperature effects in the sputtering of an organic molecule were investigated by
subjecting a well defined film of coronene to Au1 and C60 primary ions at 100 and
300 K. Strong field photoionization of the sputtered neutral flux was employed to
monitor the change in flight time and kinetic energy distributions of intact and
fragmented species.
PMID- 24347746
TI - New spectral vegetation indices based on the near-infrared shoulder wavelengths
for remote detection of grassland phytomass.
AB - This article examines the possibility of exploiting ground reflectance in the
near-infrared (NIR) for monitoring grassland phytomass on a temporal basis. Three
new spectral vegetation indices (infrared slope index, ISI; normalized infrared
difference index, NIDI; and normalized difference structural index, NDSI), which
are based on the reflectance values in the H25 (863-881 nm) and the H18 (745-751
nm) Chris Proba (mode 5) bands, are proposed. Ground measurements of
hyperspectral reflectance and phytomass were made at six grassland sites in the
Italian and Austrian mountains using a hand-held spectroradiometer. At full
canopy cover, strong saturation was observed for many traditional vegetation
indices (normalized difference vegetation index (NDVI), modified simple ratio
(MSR), enhanced vegetation index (EVI), enhanced vegetation index 2 (EVI 2),
renormalized difference vegetation index (RDVI), wide dynamic range vegetation
index (WDRVI)). Conversely, ISI and NDSI were linearly related to grassland
phytomass with negligible inter-annual variability. The relationships between
both ISI and NDSI and phytomass were however site specific. The WinSail model
indicated that this was mostly due to grassland species composition and
background reflectance. Further studies are needed to confirm the usefulness of
these indices (e.g. using multispectral specific sensors) for monitoring
vegetation structural biophysical variables in other ecosystem types and to test
these relationships with aircraft and satellite sensors data. For grassland
ecosystems, we conclude that ISI and NDSI hold great promise for non
destructively monitoring the temporal variability of grassland phytomass.
PMID- 24347747
TI - beta-Pyrazino-fused tetrarylporphyrins.
AB - A novel method for the preparation of beta-fused porphyrin dyads was developed
that exploits a one-pot reaction of 2,3-diaminoporphyrins with diethyl oxalate.
This approach provides good yields of the zinc beta-fused dyad and the
corresponding free-base, opening the way for preparation of several metal
derivatives to permit modulation of optoelectronic characteristics for commercial
applications.
PMID- 24347748
TI - Engaging Teenagers with Science Through Comics.
PMID- 24347749
TI - Structural Nested Cumulative Failure Time Models to Estimate the Effects of
Interventions.
AB - In the presence of time-varying confounders affected by prior treatment, standard
statistical methods for failure time analysis may be biased. Methods that
correctly adjust for this type of covariate include the parametric g-formula,
inverse probability weighted estimation of marginal structural Cox proportional
hazards models, and g-estimation of structural nested accelerated failure time
models. In this article, we propose a novel method to estimate the causal effect
of a time-dependent treatment on failure in the presence of informative right
censoring and time-dependent confounders that may be affected by past treatment:
g-estimation of structural nested cumulative failure time models (SNCFTMs). An
SNCFTM considers the conditional effect of a final treatment at time m on the
outcome at each later time k by modeling the ratio of two counterfactual
cumulative risks at time k under treatment regimes that differ only at time m.
Inverse probability weights are used to adjust for informative censoring. We also
present a procedure that, under certain "no-interaction" conditions, uses the g
estimates of the model parameters to calculate unconditional cumulative risks
under nondynamic (static) treatment regimes. The procedure is illustrated with an
example using data from a longitudinal cohort study, in which the "treatments"
are healthy behaviors and the outcome is coronary heart disease.
PMID- 24347750
TI - Defining the Low End of Primate Social Complexity: The Social Organization of the
Nocturnal White-Footed Sportive Lemur (Lepilemur leucopus).
AB - Whereas other species of sportive lemurs (genus Lepilemur) have been described as
living in dispersed pairs, which are characterized by spatial overlap but a lack
of affinity or affiliation between one adult male and female, existing reports on
the social organization of the white-footed sportive lemur (Lepilemur leucopus)
are conflicting, describing them as either living in dispersed one-male
multifemale systems or pairs. We conducted this study in the spiny forest of
Berenty Reserve, southern Madagascar, to clarify the social organization and to
characterize the level of social complexity of this species. We combined 1530 h
of radio-telemetry and behavioral observations over a period of 1 yr to describe
the spatiotemporal stability, size, and interindividual overlap of individual
home ranges as well as interindividual cohesiveness. Results revealed low intra-
and high intersexual home range overlap. Although most of the social units
identified consisted of dispersed pairs (N = 5), males were associated with two
adult females in two cases. Furthermore, members of a social unit were never
observed to groom each other or to share a daytime sleeping site, and
Hutchinson's and Doncaster's dynamic interaction tests indicated active avoidance
between pair partners. Low cohesiveness together with extremely low rates of
social interactions therefore arguably places Lepilemur leucopus at the low end
of primate social complexity.
PMID- 24347751
TI - Within-person variability in state anxiety across adulthood: Magnitude and
associations with between-person characteristics.
AB - Across domains of functioning, research has shown substantial within-person
variability in a number of different types of variables from one measurement
occasion to another. Using data obtained from a large sample (n = 784, 18-97
years) at three separate occasions, we examined properties and correlates of
short-term variability in a construct that by definition is prone to
fluctuations, namely state anxiety. Our results revealed that participants
exhibited sizeable across-occasion variation in state anxiety. The magnitude of
variability was unrelated to age, but was associated with a number of individual
difference characteristics such as self-reported health, aspects of personality,
well-being, and cognition. However, after taking into account mean-level
differences in state anxiety, evidence for unique associations of variability was
minimal.
PMID- 24347752
TI - Natural and constrained language production as a function of age and cognitive
abilities.
AB - Although it is often claimed that verbal abilities are relatively well maintained
across the adult lifespan, certain aspects of language production have been found
to exhibit cross-sectional differences and longitudinal declines. In the current
project age-related differences in controlled and naturalistic elicited language
production tasks were examined within the context of a reference battery of
cognitive abilities in a moderately large sample of individuals aged 18-90. The
results provide support for age-related increases in lexical sophistication and
diversity at the discourse level, and declines in grammatical complexity in
controlled and naturalistic contexts. Further, age-related decreases in facility
with complex grammatical constructions in controlled sentence production were
statistically independent of the cognitive abilities assessed in this project.
PMID- 24347754
TI - Promoting Relationship Building and Connection: Adapting an Evidence-Based
Parenting Program for Families Involved in the Child Welfare System.
AB - The high needs of youth involved in the child welfare system and the poor long
term outcomes of former foster youth represent a significant systemic challenge.
As part of a process to adapt an evidence-based parenting program for a child
welfare population, we conducted a series of focus groups with child welfare
staff, foster caregivers, and young adults who were involved in the foster system
as teens. From these focus groups we learned that, although there is a need for
evidence-based parenting programs for families involved in the child welfare
setting, one of the significant barriers to program implementation is the lack of
meaningful connection between caregivers and youth in their care. We will provide
an in-depth discussion on the proposed adaptations to make Staying Connected more
relevant for foster families, including the addition of skills training to help
overcome some of the barriers to connection. Staying Connected holds the promise
of cultivating more supportive home environments that have the capacity to
nurture youths' healthy development, including the avoidance of high-risk
behaviors.
PMID- 24347753
TI - Morphological structure in the Arabic mental lexicon: Parallels between standard
and dialectal Arabic.
AB - The Arabic language is acquired by its native speakers both as a regional spoken
Arabic dialect, acquired in early childhood as a first language, and as the more
formal variety known as Modern Standard Arabic (MSA), typically acquired later in
childhood. These varieties of Arabic show a range of linguistic similarities and
differences. Since previous psycholinguistic research in Arabic has primarily
used MSA, it remains to be established whether the same cognitive properties hold
for the dialects. Here we focus on the morphological level, and ask whether roots
and word patterns play similar or different roles in MSA and in the regional
dialect known as Southern Tunisian Arabic (STA). In two intra-modal auditory
auditory priming experiments, we found similar results with strong priming
effects for roots and patterns in both varieties. Despite differences in the
timing and nature of the acquisition of MSA and STA, root and word pattern
priming was clearly distinguishable from form-based and semantic-based priming in
both varieties. The implication of these results for theories of Arabic diglossia
and theories of morphological processing are discussed.
PMID- 24347755
TI - Discrimination hurts, but mindfulness may help: Trait mindfulness moderates the
relationship between perceived discrimination and depressive symptoms.
AB - Discriminatory experiences are not only momentarily distressing, but can also
increase risk for lasting physical and psychological problems. Specifically,
significantly higher rates of depression and depressive symptoms are reported
among people who are frequently the target of prejudice. Given the gravity of
this problem, this research focuses on an individual difference, trait
mindfulness, as a protective factor in the association between discrimination and
depressive symptoms. In a community sample of 605 individuals, trait mindfulness
dampens the relationship between perceived discrimination and depressive
symptoms. Additionally, mindfulness provides benefits above and beyond those of
positive emotions. Trait mindfulness may thus operate as a protective individual
difference for targets of discrimination.
PMID- 24347756
TI - Personality and facial morphology: Links to assertiveness and neuroticism in
capuchins (Sapajus [Cebus] apella).
AB - Personality has important links to health, social status, and life history
outcomes (e.g. longevity and reproductive success). Human facial morphology
appears to signal aspects of one's personality to others, raising questions about
the evolutionary origins of such associations (e.g. signals of mate quality).
Studies in non-human primates may help to achieve this goal: for instance, facial
width-to-height ratio (fWHR) in the male face has been associated with dominance
not only in humans but also in capuchin monkeys. Here we test the association of
personality (assertiveness, openness, attentiveness, neuroticism, and
sociability) with fWHR, face width/lower-face height, and lower face/face height
ratio in 64 capuchins (Sapajus apella). In a structural model of personality and
facial metrics, fWHR was associated with assertiveness, while lower face/face
height ratio was associated with neuroticism (erratic vs. stable behaviour) and
attentiveness (helpfulness vs. distractibility). Facial morphology thus appears
to associate with three personality domains, which may act as a signal of status
in capuchins.
PMID- 24347758
TI - Limits of Spatial Resolution for Thermography and Other Non-destructive Imaging
Methods Based on Diffusion Waves.
AB - In this work the measured variable, such as temperature, is a random variable
showing fluctuations. The loss of information caused by diffusion waves in non
destructive testing can be described by stochastic processes. In non-destructive
imaging, the information about the spatial pattern of a samples interior has to
be transferred to the sample surface by certain waves, e.g., thermal waves. At
the sample surface these waves can be detected and the interior structure is
reconstructed from the measured signals. The amount of information about the
interior of the sample, which can be gained from the detected waves on the sample
surface, is essentially influenced by the propagation from its excitation to the
surface. Diffusion causes entropy production and information loss for the
propagating waves. Mandelis has developed a unifying framework for treating
diverse diffusion-related periodic phenomena under the global mathematical label
of diffusion-wave fields, such as thermal waves. Thermography uses the time
dependent diffusion of heat (either pulsed or modulated periodically) which goes
along with entropy production and a loss of information. Several attempts have
been made to compensate for this diffusive effect to get a higher resolution for
the reconstructed images of the samples interior. In this work it is shown that
fluctuations limit this compensation. Therefore, the spatial resolution for non
destructive imaging at a certain depth is also limited by theory.
PMID- 24347757
TI - Parent Predictors of Changes in Child Behavior Problems.
AB - The present study examined whether ineffective discipline, single parent status,
social support, parent involvement, and parent depression predicted changes in
preschoolers' (N = 129) behavior problems. This study also evaluated whether
child sex and ethnicity moderated the relationships between these variables and
changes in problem behavior. Parents completed questionnaires at the beginning of
the study, and parent, teacher, and observational ratings of children's behavior
problems were collected twice during the school year. Parents' own social support
predicted improvement for boys and parent depression was associated with
worsening symptoms for girls. Single parenthood and parent involvement predicted
changes in behavior problems for the sample as a whole. Several significant
ethnic differences emerged, highlighting the importance of considering cultural
context in studies of parenting and child externalizing behavior.
PMID- 24347759
TI - Chronotherapeutics: a hype or future of chronopharmacology?
PMID- 24347760
TI - Zonisamide: a review of the clinical and experimental evidence for its use in
Parkinson's disease.
AB - The limitations of currently available therapies in addressing the non motor
symptoms of Parkinson's disease (PD) have egged on the search for newer options.
Zonisamide has been in use for epilepsy and it was serendipitously found to
improve the symptoms of PD in a patient who had both epilepsy and PD. Thereafter,
various trials were designed to assess the use of zonisamide in PD. The present
article investigates the evidence for use of zonisamide in PD from the various
clinical trials that were designed to address this issue. Furthermore, the
article also summarizes the various mechanisms of its use in PD as described in
various animal experiments. A search protocol was designed with predefined
inclusion and exclusion criteria. The databases searched were Pubmed, Ovid
medline, Cochrane and clinicaltrials.gov. The data thus generated, was fed into a
predesigned format. Most of the clinical trials on zonisamide in PD have come
from Japan. Most of these trials used the changes in the Unified Parkinson's
Disease Rating Scale (UPDRS) score as the endpoints and the most conclusive
evidence is for a dose of 25-50 mg, which caused a change in UPDRS part III
(motor symptoms). These patients were on levodopa and other drugs used for PD
during the trials. One of the clinical trials conducted in Spain investigates the
use of zonisamide in impulse control disorders among 15 patients of PD. Among the
many mechanisms postulated, a reduction in levodopa induced quinone formation,
protection against mitochondrial impairment and an increase in astroglial
cysteine transport, an inhibition of microglial activation, monoamine oxidase-B
(MAO-B) inhibition, an increased dopamine release and blockade of calcium
channels are the most cited. There is evidence for use of zonisamide in PD in
addition to levodopa and other therapies for control of motor symptoms. For now,
the evidence for its use in control of non motor symptoms in PD is not enough and
needs to be investigated further.
PMID- 24347761
TI - The effect of Chinese medicine Pu-Ren-Dan on pancreatic angiogenesis in high fat
diet/streptozotocin-induced diabetic rats.
AB - OBJECTIVES: The islet vascular system is critical for beta-cell function. This
study investigated the antidiabetic effect of the Chinese Pu-Ren-Dan (PRD) recipe
by regulating the pancreatic angiogenic factors in T2DM rats. MATERIALS METHODS:
High fat diet/streptozotocin-induced obese type-2 diabetes mellitus rats were
developed and treated with PRD for 4 weeks. Then glucolipid metabolism, insulin
secretion, pancreatic blood flow, ultrastructure of islet beta-cell, histological
changes of islet and protein expressions of pancreatic angiogenic factors were
investigated. RESULTS: PRD-reduced T2DM rats' body weight and blood glucose level
resisted the lipid metabolism disturbance, and ameliorated the insulin resistance
and beta-cell function. In addition, the histological and morphological studies
proved that PRD could maintain the normal distribution of endocrine cell in islet
and normal ultrastructure of beta cell. An increased pancreatic blood flow was
observed after the PRD treatment. In the investigation of pancreatic angiogenic
factors, PRD inhibited the decreased expression of VEGF and Ang-1, and reversed
the reduction of VEGFR2 and Tie2 phosphorylation in T2DM rats; the Ang-2 and
TGFbeta expression were up-regulated by PRD while PKC was activated; endostatin
and angiostatin were down-regulated by PRD. CONCLUSIONS: The results suggest that
increasing VEGF expression, regulating VEGF/VEGFR2 signaling, stimulating Ang
1/Tie-2 signaling pathway, and inhibiting PKC-TGFbeta signaling and
antiangiogenic factors might be the underlying mechanism of PRD's antidiabetic
effect.
PMID- 24347762
TI - Withania somnifera ameliorates lead-induced augmentation of adrenergic response
in rat portal vein.
AB - OBJECTIVES: Present study was undertaken to elucidate the ameliorating potential
of Withania somnifera root extract (WRE) against lead-induced augmentation of
adrenergic response in rat portal vein. MATERIALS AND METHODS: In-vitro studies
were conducted on effect of lead alone and lead+WRE on rat-isolated portal vein
while in-vivo studies were done in three groups of 12 rats each; Group-II and III
received 0.5% lead acetate and 1.0% WRE + 0.5% lead acetate, respectively, in
drinking water for 12 weeks whereas group-I served as control. Adrenaline and
noradrenaline levels in brain and blood were determined by HPLC assay while
vascular reactivity of portal vein to lead and WRE was determined by measuring
the isometric tension. RESULTS: Following in-vitro exposure, lead did not alter
the contractile effect of phenylephrine. In-vivo studies revealed that
contractile effect of lead on portal vein was significantly potentiated and it
was antagonized by prazosin (10(-7) M) and WRE (1%). WRE treatment significantly
reduced elevated blood noradrenaline (37.80%) and restored noradrenaline level in
brain (39.39%) in lead-exposed animals. These values were almost comparable to
the control group. But it failed to significantly affect the blood and brain
adrenaline levels. CONCLUSIONS: Results suggest that following pre-exposure of
rats to WRE, lead-induced augmentation of alpha 1-adrenoceptors mediated response
was reversed possibly by regulating catecholamine release from nerve endings.
Thus, WRE may be useful in therapeutic management of lead-induced hypertension.
PMID- 24347763
TI - Evaluation of antiangiogenic and antiproliferative potential of the organic
extract of green algae Chlorella pyrenoidosa.
AB - OBJECTIVE: algae isolates obtained from fresh and marine resources could be one
of the richest sources of novel bioactive secondary metabolites expected to have
pharmaceutical significance for new drug development. This study was conducted to
evaluate the antiangiogenic and antiproliferative activity of Chlorella
pyrenoidosa in experimental models of angiogenesis and by MTT assay. MATERIALS
AND METHODS: lyophilized extract of C. pyrenoidosa was extracted using
dichloromethane/methanol (2:1), concentrated and vacuum evaporated to obtain the
dried extract. The crude extract was evaluated in the vascular endothelial growth
factor (VEGF)-induced angiogenesis in in ovo chick chorioallantoic membrane assay
(CAM) at various concentrations (n = 8) using thalidomide and normal saline as
positive and untreated control groups, respectively. The crude extract was also
subjected to the antiangiogenic activity in the silver nitrate/potassium nitrate
cautery model of corneal neovascularization (CN) in rats where topical
bevacizumab was used as a positive control. The vasculature was photographed and
blood vessel density was quantified using Aphelion imaging software. The extract
was also evaluated for its anti proliferative activity by microculture
tetrazolium test (MTT) assay using HeLa cancer cell line (ATCC). RESULTS: VEGF
increased the blood vessel density by 220% as compared to normal and thalidomide
treatment decreased it to 67.2% in in ovo assay. In the in-vivo CN model, the
mean neovascular density in the control group, the C. pyrenoidosa extract and
bevacizumab group were found to be 100%, 59.02%, and 32.20%, respectively. The
Chlorella pyrenoidosa extract negatively affected the viability of HeLa cells. An
IC50 value of the extract was 570 MUg/ml, respectively. CONCLUSION: a significant
antiangiogenic activity was observed against VEGF-induced neovascularization and
antiproliferative activity by MTT assay. In this study, it could be attributed
that the activity may be due to the presence of secondary metabolites in the C.
pyrenoidosa extract.
PMID- 24347764
TI - Neuroprotective activity of gossypin from Hibiscus vitifolius against global
cerebral ischemia model in rats.
AB - OBJECTIVES: The objective of this study is to evaluate the neuroprotective effect
of gossypin (isolated from Hibiscus vitifolius) against global cerebral
ischemia/reperfusion (I/R) injury-induced oxidative stress in rats. MATERIALS AND
METHODS: Sprague Dawlet rats of wither gender were used in the study. Evaluation
of cerbroprotective activity of bioflavonoid gossypin (in 5, 10 and 20 mg/kg oral
doses) isolated from H. vitifolius was carried out by using the global cerebral
I/R model by bilateral carotid artery occlusion for 30 min, followed by 24 h
reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated
along with histopathological studies. RESULT: Gossypin showed dose-dependent
neuroprotective activity by significant decrease in lipid peroxidation (P <
0.001) and increase in the superoxide dismutase, catalase, glutathione and total
thiol levels in gossypin treated groups when compared to control group. Cerebral
infarction area was markedly reduced in gossypin treated groups when compared to
control group. CONCLUSION: Gossypin showed potent neuroprotective activity
against global cerebral I/R injury-induced oxidative stress in rats.
PMID- 24347765
TI - Effect of melatonin and gabapentin on anxiety and pain associated with
retrobulbar eye block for cataract surgery: a randomized double-blind study.
AB - OBJECTIVES: To compare the effect of melatonin and gabapentin on anxiety, pain,
sedation scores, and satisfaction of surgeon in patients of cataract surgery.
MATERIALS AND METHODS: One hundred thirty patients aged between 35 and 85 years
scheduled for cataract surgery were randomly allocated to three study groups to
receive melatonin (6 mg), gabapentin (600 mg) or placebo 90 min before arrival in
the operating room. Pain, anxiety, and sedation scores during block and surgery
as well as the surgeon's satisfaction with the surgery were assessed. RESULTS:
Anxiety scores decreased significantly in melatonin and gabapentin groups
compared to the placebo group after premedication and extended to early
postoperative period. The level of anxiety showed no statistically significant
difference between melatonin and gabapentin groups at any time of measurement.
There were significant differences between the pain scores during retrobulbar
placement in gabapentin versus placebo (95% CI 3 to 4; P = 0.001) and melatonin
(95% CI 3 to 4; P = 0.040) groups. Also, there were significant differences
between the sedation scores during retrobulbar placement in gabapentin and
placebo groups (95% CI 2 to 2.5; P = 0.046). The difference in sedation scores
during retrobulbar placement in melatonin versus gabapentin and placebo groups
was not significant. Neither the intraoperative pain scores nor the postoperative
pain scores were different between the three groups. The surgeon reported similar
quality of operation conditions during surgery for the three study groups.
CONCLUSION: The level of anxiety was significantly lower with both anxiolytic
drugs compared to placebo. Furthermore, gabapentin decreased the pain and
improved the sedation scores only during retrobulbar placement compared to the
placebo.
PMID- 24347766
TI - Development of a teaching module for parenteral drug administration and objective
structured practical examination stations in pharmacology.
AB - OBJECTIVES: Safe parenteral drug administration includes preparation of safe
medication for administration. Training medical students is crucial to minimize
medication administration errors. The study aims to develop a module to teach
drug preparation skills and to develop objective structured practical examination
(OSPE) stations to assess these skills. Students' perceptions regarding the
module were also assessed. MATERIALS AND METHODS: A module was developed to teach
following skills to 2(nd) year medical students: Aspiration of a drug from the
ampule, aspiration of the drug from the vial, aspiration of the drug in powdered
form from vial (reconstitution), and setting up an intravenous (IV) infusion. A
randomized case control study design was used to establish the validity of OSPE
stations. Student volunteers were grouped into case (n = 20) and control groups
(n = 20) by simple randomization. The test group watched videos of skills and
received demonstration of skills and a practice session before OSPE, whereas the
control group watched videos before the OSPE and received demonstration and a
practice session only after the OSPE. Each student was assessed by two faculty
members during OSPE using a validated checklist. Mean OSPE scores of control and
test groups were compared using independent samples t-test. Interrater
reliability and concurrent validity of stations were analyzed using interclass
correlation coefficient (ICC) and Pearson correlation, respectively. Students'
responses were expressed as median and interquartile range. RESULTS: The response
rate in the questionnaire was 100%. Significant difference between mean scores (P
< 0.05) of test and control groups revealed fulfillment of construct validity of
OSPE stations. Interrater reliability (ICC > 0.7) and concurrent validity (r
value > 7) of all the stations was high. Perceptions revealed acceptability of
module and OSPE stations by students (median 4, scale 1-5). CONCLUSIONS: A module
to teach drug preparation skills was developed and along with valid and reliable
OSPE stations that were acceptable to students. The study demonstrated that
students acquire better skills through teaching than merely watching these skills
in videos.
PMID- 24347767
TI - Sucrose-induced analgesia in mice: role of nitric oxide and opioid receptor
mediated system.
AB - BACKGROUND: The mechanism of action of sweet substance-induced analgesia is
thought to involve activation of the endogenous opioid system. The nitric oxide
(NO) pathway has a pivotal role in pain modulation of analgesic compounds such as
opioids. OBJECTIVES: We investigated the role of NO and the opioid receptor
mediated system in the analgesic effect of sucrose ingestion in mice. MATERIALS
AND METHODS: We evaluated the effect of intraperitoneal administration of 10
mg/kg of NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) and 20
mg/kg of opioid receptor antagonist, naltrexone on the tail flick response in
sucrose ingesting mice. RESULTS: Sucrose ingestion for 12 days induced a
statistically significant increase in the latency of tail flick response which
was unmodified by L-NAME, but partially inhibited by naltrexone administration.
CONCLUSIONS: Sucrose-induced nociception may be explained by facilitating the
release of endogenous opioid peptides. Contrary to some previously studied pain
models, the NO/cyclic guanosine monophosphate (cGMP) pathway had no role in
thermal hyperalgesia in our study. We recommend further studies on the
involvement of NO in other animals and pain models.
PMID- 24347768
TI - Reversal of multidrug resistance by 5,5'-dimethoxylariciresinol-4-O-beta-D
glucoside in doxorubicin-resistant human leukemia K562/DOX.
AB - OBJECTIVE: The objective of this study was to investigate the reversal effects of
5,5'-dimethoxylariciresinol-4'-O-beta-D-glucoside (DMAG) extracted from
traditional Chinese medicines Mahonia on multidrug resistance (MDR) of human
leukemia cells to chemotherapeutic agents. MATERIALS AND METHODS: MTT(3-(4,5
Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to
determine the effect of DMAG on doxorubicin sensitivity to K562/DOX cells.
Propidium iodide /Hoechst 33342 double staining assay was used to investigate the
effect of DMAG on doxorubicin-induced cellular apoptosis. Intracellular
accumulation of doxorubicin and rhodamine 123 assay were performed to evaluate
the effect of DMAG on drugs efflux activity of P-glycoprotein. RESULTS: DMAG
significantly enhanced the doxorubicin cytotoxicity to K562/DOX cells. In the
presence of 1.0 MUM of DMAG, the IC50 of doxorubicin decreased from 34.93 +/-
1.37 MUM to 12.51 +/- 1.28 MUM. DMAG of 1.0 MUM significantly enhanced
doxorubicin-induced cell apoptosis in K562/DOX cells and the enhancement was time
dependent. A significant increase in accumulation of doxorubicin in the presence
of DMAG was observed. After treatment of the K562/DOX cells for 1 h with 15.0 MUM
doxorubicin alone, the fluorescence intensity was 33093.12. With the addition of
1.0 MUM of DMAG, the fluorescence intensity of doxorubicin was 2.3-fold higher. A
significant increase of accumulation of rhodamine 123 in the presence of DMAG was
also observed. With the addition of 1.0 MUM of DMAG, the fluorescence intensity
was increased by 49.11% compared with rhodamine 123 alone. CONCLUSION: DMAG was
shown to effectively enhance chemosensitivity of resistant cells, which makes it
might be a suitable candidate for potential MDR-reversing agents.
PMID- 24347769
TI - Use of potentially inappropriate medications in hospitalized elderly at a
teaching hospital: a comparison between Beers 2003 and 2012 criteria.
AB - OBJECTIVES: To detect the prevalence and pattern of use of Potentially
inappropriate medications (PIMs) in hospitalized elderly patients of a tertiary
care teaching hospital using Beers 2012 criteria and to compare the same with
Beers 2003 criteria. MATERIALS AND METHODS: Prescriptions of the elderly patients
aged 65 years and above were collected from the medicine ward and analyzed. PIMs
were identified with help of Beers 2003 and Beers 2012 criteria and comparison
was made between the two criteria. Predictors associated with use of PIM were
identified using bivariate and multivariate logistic regression analysis.
RESULTS: A total of 210 patients received 2,267 drugs. According to Beers 2003
criteria, 60 (28.57%) elderly patients received at least one PIM and 2.9% drugs
were prescribed inappropriately. According to Beers 2012 criteria, 84 (40%)
elderly received at least one PIM while 22 (10.47%) received multiple PIMs and
about 5% drugs were prescribed inappropriately. The most commonly prescribed PIM
was mineral oil-liquid paraffin (30, 14.3%) followed by spironolactone (25,
11.9%), digoxin (19, 9%), and benzodiazepines (14, 6.7%). There was a significant
association between the number of patients receiving more than six drugs and the
use of PIMs (P < 0.01). Use of more than 10 drugs was a significant predictor for
use of PIMs in the elderly. CONCLUSION: The study shows high prevalence of
prescribing PIMs in hospitalized elderly patients. Beers 2012 criteria are more
effective in identifying PIMs than Beers 2003 criteria.
PMID- 24347770
TI - Parenteral polymyxins: assessing efficacy and safety in critically ill patients
with renal dysfunction.
AB - OBJECTIVES: Studies have established the effectiveness and safety of polymyxins
in treating multidrug resistant (MDR) pathogens. However, the challenge is
whether these nephrotoxic drugs can be administered in compromised renal states.
The present study was undertaken to establish their role in such patients. The
effectiveness and nephrotoxicity of polymyxins in critically ill-patients
harboring MDR Gram-negative bacteria with already compromised renal functions was
compared with those with normal renal functions. MATERIALS AND METHODS: This
retrospective cohort study (March 2008-March 2010) was conducted in the intensive
care unit of a tertiary care hospital. A total of 48 eligible critically ill
patients receiving polymyxins were enrolled. A comparison was carried out (length
of stay in hospital, mortality, renal function) between patients with acute
kidney injury (AKI, n = 18; defined by the RIFLE classification) and patients
with normal renal function (non-AKI, n = 30). RESULTS: Patients with baseline AKI
had a significantly higher adjusted mortality rate at admission when compared
with the non-AKI group. At the end of therapy with polymyxins, 26.66% non-AKI
patients developed renal dysfunction while 38.88% of patients in the AKI group
had worsening of renal function (P = 0.006). However, there was no significant
difference in the length of hospital stay (23.9 +/- 13.24 vs. 30.5 +/- 22.50; P =
0.406) and overall mortality (44.4% vs. 36.7%; P = 0.76) between two groups.
CONCLUSION: Polymyxins can be administered in AKI patients with favorable results
provided used judiciously with strict monitoring of renal functions, dose
modification according to creatinine clearance and aggressive fluid management.
PMID- 24347771
TI - Granulocyte-colony stimulating factor improves Parkinson's disease associated
with co-morbid depression: an experimental exploratory study.
AB - INTRODUCTION: The present study was designed to evaluate the effect of
granulocyte-colony stimulating factor (G-CSF) in the treatment of Parkinson's
disease (PD), the second most common neurodegenerative disease characterized by
muscle and movement disorder, often associated with depression. PD is very
difficult to treat. Hence, the present study was aimed to evaluate the effect of
G-CSF in PD associated with depression. MATERIALS AND METHODS: Adult Wistar male
rats weighing about 180-250 g were selected and divided into five groups in
parallel designed method namely; control group (n = 5); sham operated group (n =
5); Vehicle group (n = 5); G-CSF group (70 MUg/kg, s.c.) (n = 5) and L-DOPA group
(n = 5). The rats were treated with 6-hydroxydopamine (6-OHDA) on day 0 and then
treatment was continued for 14 day of L-DOPA/carbidopa, whereas G-CSF (70 MUg/kg,
s.c.) was given from day 1 to 6. Thereafter, adhesive removal and forced swim
tests were conducted to evaluate the behavioral outcome of G-CSF treatment. The
finding was correlated and analyzed with Nissl staining findings for the final
conclusion. RESULTS: The behavioral parameters were assessed and found to be
ameliorate the symptoms of Parkinson's and reduced the depression like behavior
in PD. The histological findings were supported the behavioral findings and
showed pathological improvement. CONCLUSION: As a preliminary work, the present
study first time suggested that G-CSF have a potential role in PD and associated
depression.
PMID- 24347772
TI - An evaluation of knowledge of pharmacovigilance among nurses and midwives in
Turkey.
AB - This study aimed to evaluate the awareness of nurse/midwives regarding
pharmacovigilance as well as their knowledge and experience in identifying and
reporting adverse reactions of drugs. Nurse/midwives (n = 329), working in four
state hospitals, were provided a questionnaire with a view of identifying their
knowledge and skills pertaining to pharmacovigilance. Around 45% of the
participants claimed to have knowledge of pharmacovigilance but only 23.3% of
them could define it correctly. Although 24.3% of the participants acknowledged
that adverse reactions should be reported to a centre, only 1.2% of them named
this centre (Turkey Pharmacovigilance Centre-TUFAM). The present study indicates
that nurse/midwives have insufficient knowledge of pharmacovigilance practices.
Hence, it is essential to include pharmacovigilance training in their
undergraduate and graduate education programs, and to promote reporting of
adverse reactions.
PMID- 24347773
TI - Prevention of injection pain due to propofol by dezocine: a comparison with
lidocaine.
AB - OBJECTIVES: The aim of this study was to investigate the efficacy of dezocine
(DEZ) versus placebo control (CON) and 2% lidocaine (LID) in prevention of
injection pain due to DEZ. MATERIALS AND METHODS: A prospective randomized double
blind, placebo-CON study was conducted in 75 adults, American Society of
Anesthesiologists physical status I or II, scheduled to undergo an elective
surgery. A total of 25 patients were randomly assigned to one of the three
groups, thus CON, group LID and group DEZ. The groups received either 2 ml of
normal saline or 2 ml 2% LID or 2 mg/2 ml DEZ, respectively, as pre-treatment.
Propofol was injected 1 min later. A blinded researcher assessed the patient's
pain level using a four point verbal rating scale. RESULTS: Less patients
experienced pain due to propofol injection in the LID (40%) and DEZ (28%) groups
compared with the CON (84%) group (P < 0.05). Six patients (24%) in the CON group
reported severe pain during propofol injection but none in the other two groups.
CONCLUSION: Pre-treatment with DEZ decreases propofol injection pain as
effectively as LID.
PMID- 24347774
TI - A comparative study to evaluate efficacy, safety and cost-effectiveness between
Whitfield's ointment + oral fluconazole versus topical 1% butenafine in tinea
infections of skin.
AB - AIMS AND OBJECTIVES: The aim of this study is to compare the efficacy, safety and
cost-effectiveness of topical Whitfield's ointment plus oral fluconazole with
topical 1% butenafine in tinea infections of the skin. MATERIALS AND METHODS:
Patients were randomly allocated to the two treatment groups and advised to apply
either agent topically twice-a-day for 4 weeks on the lesions and fluconazole
(150 mg) was administered once a week for 4 weeks in the study group applying
Whitfield's ointment. Patients were followed-up at an interval of 10 days for
clinical score and global evaluation response was assessed at baseline and during
each follow-up. RESULTS: Out of 120 patients enrolled in the study 103 completed
the study. Patients treated with Whitfield's ointment and oral fluconazole
reduced mean sign and symptom score from 8.81 +/- 0.82 to 0.18 +/- 0.59 while
butenafine treated patients reduced it from 8.88 +/- 0.53 to 0.31 +/- 0.67 at the
end of the treatment. Nearly, 98% patients were completely cleared of the lesion
on the 3(rd) follow-up with both treatments. CONCLUSION: Whitfield's ointment
with oral fluconazole is as efficacious, safe and cost-effective as compared with
1% butenafine in tinea infections of the skin.
PMID- 24347775
TI - Levofloxacin and furazolidone induced toxic epidermal necrosis.
AB - Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a severe
cutaneous drug reaction with a high mortality. Immune response is the possible
cause in its pathogenesis. Levofloxacin is one of the most commonly used
quinolones and has been reported to cause of TEN. On the other hand, furazolidone
was proposed to augment the action of immediate hypersensitivity of levofloxacin
by its cytotoxic effect and by the generation of free radicals. Here, we present
a case of TEN where, levofloxacin and furazolidone were the probable cause of
these adverse drug reactions.
PMID- 24347776
TI - Allopurinol induced erythroderma.
AB - Allopurinol, a widely prescribed urate lowering agent is responsible for various
adverse drug reactions, including erythroderma. A 45-year-old male patient was
admitted with the complaints of fever, redness and scaling all over the body
after 3-4 weeks of allopurinol treatment for asymptomatic hyperuricemia. Elevated
liver enzymes were detected in his blood analysis. Skin biopsy was consistent
with drug induced erythroderma. Allopurinol was stopped and steroids were
started. Patient improved over a period of 2 weeks.
PMID- 24347777
TI - Sodium valproate induced priapism in an adult with bipolar affective disorder.
AB - Priapism is defined as a prolonged and persistent, painful erection of the penis
without sexual stimulation or arousal. There have been a few case report of
priapism resulting from the use of antipsychotics. In our case, a 48-year-old
male patient with a bipolar affective disorder was experiencing recurrent
priapism with sodium valproate. The condition was found to resolve on stopping
sodium valproate. There are no known case reports of similar complication with
sodium valproate alone.
PMID- 24347778
TI - Pott's disease and hypercalcemia in a patient with rheumatoid arthritis receiving
methotrexate monotherapy.
AB - Methotrexate (MTX) may have adverse effects on multiple organs and system. A few
cases of pulmonary tuberculosis in-patients with rheumatoid arthritis (RA) while
receiving MTX monotherapy has been reported in the literature. We submit a case
of vertebral tuberculosis with hypercalcemia in a patient receiving MTX
monotherapy. Patient with RA taking MTX for 15 years developed pancytopenia, skin
necrosis, tuberculous spondylodiscitis and hypercalcemia. The present case showed
adverse effects of MTX therapy may occur even after years of continuous
treatment. Due to pancytopenia in older patients, life-threatening tuberculosis
at unusual sites may develop.
PMID- 24347779
TI - A rare case of imatinib-induced erythroderma.
AB - Imatinib, a specific tyrosine kinase inhibitor is a newer anticancer agent, which
has shown excellent efficacy in managing chronic myeloid leukemia. It is
generally well tolerated with few side effects. Most commonly reported adverse
events are maculopapular eruptions and periorbital edema. Severe adverse
reactions are seen in 5% of patients. Exfoliative dermatitis has been very rarely
reported with this drug. We report a case of a 52-year-old male who initially
presented with a maculopapular rash and developed erythroderma on continuation of
the drug.
PMID- 24347780
TI - Phenytoin-induced cerebellar atrophy in an epileptic boy.
AB - Epilepsy is an important health problem due to its high prevalence and potential
for causing long-term morbidity. It is commonly treated in children with
phenytoin sodium. It has wide pharmacokinetic variability and a narrow
therapeutic range that leads to toxicity. Here, we report a case of phenytoin
induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the
hospital with a viral infection.
PMID- 24347781
TI - Pregabalin-induced self-harm behavior.
AB - Antiepileptic Drugs (AEDs) such as lamotrigine, gabapentin, and oxcarbazepine may
have the potential to increase the risk of self-harm or suicidal behavior. We
report a case of pregabalin-induced self-inflicted multiple injuries on forearm
after its continuous use. This is an interesting adverse drug reaction (ADR) that
is rare, unusual, and potentially serious.
PMID- 24347782
TI - Piperazine citrate induced myoclonus in a child.
PMID- 24347783
TI - Drug safety guidelines: are they effective?
PMID- 24347784
TI - Fatal anaphylactic reaction to iron sucrose in pregnancy: iron-induced Kounis
syndrome?
PMID- 24347785
TI - The smoked drum.
PMID- 24347787
TI - A practical workflow for making anatomical atlases for biological research.
AB - The anatomical atlas has been at the intersection of science and art for
centuries. These atlases are essential to biological research, but high-quality
atlases are often scarce. Recent advances in imaging technology have made high
quality 3D atlases possible. However, until now there has been a lack of
practical workflows using standard tools to generate atlases from images of
biological samples. With certain adaptations, CG artists' workflow and tools,
traditionally used in the film industry, are practical for building high-quality
biological atlases. Researchers have developed a workflow for generating a 3D
anatomical atlas using accessible artists' tools. They used this workflow to
build a mouse limb atlas for studying the musculoskeletal system's development.
This research aims to raise the awareness of using artists' tools in scientific
research and promote interdisciplinary collaborations between artists and
scientists. This video (http://youtu.be/g61C-nia9ms) demonstrates a workflow for
creating an anatomical atlas.
PMID- 24347788
TI - Electrophilic C-H Borylation and Related Reactions of B-H Boron Cations.
AB - Catalytic procedures are described for aminedirected borylation of aliphatic and
aromatic tertiary amine boranes. Sequential double borylation is observed in
cases where two or more C-H bonds are available that allow 5-center or 6-center
intramolecular borylation. The HNTf2 catalyzed borylation of benzylamine boranes
provides a practical means for the synthesis of ortho-substituted arylboronic
acid derivatives, suitable for Suzuki-Miyaura cross-coupling applications.
PMID- 24347786
TI - Slave systems in verbal short-term memory.
AB - BACKGROUND: The model of performance in short-term memory (STM) tasks that has
been most influential in cognitive neuropsychological work on deficits of STM is
the "working memory" model mainly associated with the work of Alan Baddeley and
his colleagues. AIM: This paper reviews the model. We examine the development of
this theory in studies that account for STM performances in normal (non-brain
damaged) individuals, and then review the application of this theory to
neuropsychological cases and specifications, modifications, and extensions of the
theory that have been suggested on the basis of these cases. Our approach is to
identify the major phenomena that have been discussed and to examine selected
papers dealing with those phenomena in some detail. MAIN CONTRIBUTION: The main
contribution is a review of the WM model that includes both normative and
neuropsychological data. CONCLUSIONS: We conclude that the WM model has many
inconsistencies and empirical inadequacies, and that cognitive neuropsychologists
might benefit from considering other models when they attempt to describe and
explain patients' performances on STM tasks.
PMID- 24347789
TI - Lewis Base Activation of Lewis Acids - Group 13. In Situ Generation and Reaction
of Borenium Ions.
AB - A variety of Lewis bases were combined with 9-BBN-NTf2 to establish the
requirements for the generation of borenium cations. Five different types of
behavior were found, but the most interesting was the combination of Et3N, DABCO,
2,6-lutidine, or Ph3P=S which formed borenium ions exclusively even in sub- or
superstoichiometric quantities. The 9-BBN borenium ion complex of 2,6-lutidine
was found to rapidly catalyze the hydrosilylation of a variety of ketones in the
presence of Et3SiH. Preliminary mechanistic experiments suggest that the
reduction involves borenium ion activation of Et3SiH and not the ketone.
PMID- 24347794
TI - FAS and FASL gene polymorphisms are not associated with hepatitis B virus
infection based on a case-control study in a Brazilian population.
AB - OBJECTIVE: This study investigated the association of the single nucleotide
polymorphisms (SNPs) in the FAS and FASL genes with the outcome of hepatitis B
virus (HBV) infection. METHODS: Blood samples were collected from 116 HBV
infected patients at the Hospital of the Santa Casa de Misericordia Foundation
(Belem, PA, Brazil). Seronegative individuals were used as controls. DNA samples
were extracted from the leukocytes and assayed using the polymerase chain
reaction (PCR) followed by RFLP analysis with restriction endonucleases. RESULTS:
The frequencies of the mutant genotypes for -670FAS (GG), Ivs2nt-124FASL (GG),
Ivs3nt-169FASL (DeltaT/DeltaT), and -844FASL (TT) were higher in the HBV
patients, and the FAS-1377AA genotype was more frequent in the control group;
however, the differences between the allele and genotype frequencies were not
statistically significant. When the HBV patient population was divided into two
groups (inactive carriers and active chronic hepatitis patients), the mutant
genotypes were found to be more prevalent in the active chronic hepatitis group
with respect to the FAS gene polymorphisms; however, this difference was not
statistically significant. CONCLUSIONS: The results suggest that the
polymorphisms in FAS and FASL genes are not associated with HBV infection or even
with the natural history of the infection in the Brazilian Amazon region.
PMID- 24347795
TI - Circulating autoantibodies to LGALS3BP: a novel biomarker for cancer.
AB - PURPOSE: Circulating autoantibodies have been extensively investigated as
possible markers for early diagnosis of cancer. The present study was carried out
to investigate whether anti-LGALS3BP IgG autoantibodies could be classified as a
biomarker for malignant tumors. METHODS: An in-house developed enzyme-linked
immunosorbent assay was used to detect autoantibodies to LGALS3BP in sera from 71
patients with various types of cancers and 54 healthy subjects matched by age and
gender. RESULTS: Patients with cancer have significant higher circulating levels
of anti-LGALS3BP antibodies as compared to control subjects (P < 0.001). The test
has a sensitivity of 33% and a specificity of 98%. CONCLUSIONS: Anti-LGALS3BP IgG
autoantibodies are a promising biomarker for malignant tumors and could play a
role in the development of a multimarker assay for the early detection of cancer.
PMID- 24347797
TI - CD14 gene variants and their importance for childhood croup, atopy, and asthma.
AB - BACKGROUND: The CD14 gene has an important role in the detection of inflammatory
provoking pathogens and in the ensuing signaling of the innate immune response.
We assessed the role of CD14 C-159T, G-1359T in the expression of asthma, croup,
and allergy in Canadian school children of ages 6 to 14 years. METHODS: Children
attending schools in a rural community participated in a cross-sectional survey
of respiratory health. Following consent, we conducted clinical assessments to
collect buccal swabs for genotyping and perform skin prick testing (SPT) to
determine atopic status. Genotyping and SPT results were available for 533 and
499 children, respectively. Separate multivariable analyses that included both
polymorphisms were conducted for each phenotype. RESULTS: The prevalence of
asthma, allergy, and croup was 18.6%, 22.4%, and 6.6%, respectively. Children
with the T/T variant of CD14 G-1359T were more likely to have physician diagnosed
asthma (26.8%). Children with C/C variant of CD14 C-159T had a significantly
lower prevalence of croup (2.6%). Haplotype analyses of the two CD14
polymorphisms showed that individuals with the T|T haplotype combination were
significantly more likely to have asthma (P = 0.014). CONCLUSIONS: In this study,
CD14 variants are important for the expression of croup and asthma but not atopy.
PMID- 24347796
TI - Adiposity measurements by BMI, skinfolds and dual energy X-ray absorptiometry in
relation to risk markers for cardiovascular disease and diabetes in adult males.
AB - BACKGROUND: Choice of adiposity measure may be important in the evaluation of
relationships between adiposity and risk markers for cardiovascular disease and
diabetes. AIM: We explored the strengths of risk marker associations with BMI, a
simple measure of adiposity, and with measures provided by skinfold thicknesses
and dual energy X-ray absorptiometry (DXA). SUBJECTS AND METHODS: We evaluated in
three subgroups of white males (n = 156-349), participating in a health screening
program, the strengths of relationship between measures of total and regional
adiposity and risk markers relating to blood pressure, lipids and lipoproteins,
insulin sensitivity, and subclinical inflammation. RESULTS: Independent of age,
smoking, alcohol intake, and exercise, the strongest correlations with adiposity
measures were seen with serum triglyceride concentrations and indices of insulin
sensitivity, with strengths of association showing little difference between BMI
and skinfold and DXA measures of total and percent body fat (R = 0.20-0.46, P <
0.01). Significant but weaker associations with adiposity were seen for serum HDL
cholesterol and only relatively inconsistent associations with adiposity for
total and LDL cholesterol and indices of subclinical inflammation. CONCLUSIONS:
BMI can account for variation in risk markers in white males as well as more
sophisticated measures derived from skinfold thickness measurements or DXA
scanning.
PMID- 24347801
TI - Indigenous Principles of Wild Harvest and Management: An Ojibway Community as a
Case Study.
PMID- 24347800
TI - Future Scenarios as a Research Tool: Investigating Climate Change Impacts,
Adaptation Options and Outcomes for the Great Barrier Reef, Australia.
AB - Climate change is a significant future driver of change in coastal social
ecological systems. Our knowledge of impacts, adaptation options, and possible
outcomes for marine environments and coastal industries is expanding, but remains
limited and uncertain. Alternative scenarios are a way to explore potential
futures under a range of conditions. We developed four alternative future
scenarios for the Great Barrier Reef and its fishing and tourism industries
positing moderate and more extreme (2-3 degrees C above pre-industrial
temperatures) warming for 2050 and contrasting 'limited' and 'ideal' ecological
and social adaptation. We presented these scenarios to representatives of key
stakeholder groups to assess the perceived viability of different social
adaptation options to deliver desirable outcomes under varied contexts.
PMID- 24347799
TI - Risk factors for mortality in hemodialysis patients: two-year follow-up study.
AB - BACKGROUND: End-stage renal disease (ESRD) patients under hemodialysis (HD) have
high mortality rate. Inflammation, dyslipidemia, disturbances in erythropoiesis,
iron metabolism, endothelial function, and nutritional status have been reported
in these patients. Our aim was to identify any significant association of death
with these disturbances, by performing a two-year follow-up study. METHODS AND
RESULTS: A large set of data was obtained from 189 HD patients (55.0% male; 66.4
+/- 13.9 years old), including hematological data, lipid profile, iron
metabolism, nutritional, inflammatory, and endothelial (dys)function markers, and
dialysis adequacy. RESULTS: 35 patients (18.5%) died along the follow-up period.
Our data showed that the type of vascular access, C-reactive protein (CRP), and
triglycerides (TG) are significant predictors of death. The risk of death was
higher in patients using central venous catheter (CVC) (Hazard ratio [HR] = 3.03,
95% CI = 1.49-6.13), with higher CRP levels (fourth quartile), compared with
those with lower levels (first quartile) (HR = 17.3, 95% CI = 2.40-124.9).
Patients with higher TG levels (fourth quartile) presented a lower risk of death,
compared with those with the lower TG levels (first quartile) (HR = 0.18, 95% CI
= 0.05-0.58). CONCLUSIONS: The use of CVC, high CRP, and low TG values seem to be
independent risk factors for mortality in HD patients.
PMID- 24347802
TI - Fast Censored Linear Regression.
AB - Weighted log-rank estimating function has become a standard estimation method for
the censored linear regression model, or the accelerated failure time model. Well
established statistically, the estimator defined as a consistent root has,
however, rather poor computational properties because the estimating function is
neither continuous nor, in general, monotone. We propose a computationally
efficient estimator through an asymptotics-guided Newton algorithm, in which
censored quantile regression methods are tailored to yield an initial consistent
estimate and a consistent derivative estimate of the limiting estimating
function. We also develop fast interval estimation with a new proposal for
sandwich variance estimation. The proposed estimator is asymptotically equivalent
to the consistent root estimator and barely distinguishable in samples of
practical size. However, computation time is typically reduced by two to three
orders of magnitude for point estimation alone. Illustrations with clinical
applications are provided.
PMID- 24347798
TI - Oxidative stress-related biomarkers in essential hypertension and ischemia
reperfusion myocardial damage.
AB - Cardiovascular diseases are a leading cause of mortality and morbidity worldwide,
with hypertension being a major risk factor. Numerous studies support the
contribution of reactive oxygen and nitrogen species in the pathogenesis of
hypertension, as well as other pathologies associated with ischemia/reperfusion.
However, the validation of oxidative stress-related biomarkers in these settings
is still lacking and novel association of these biomarkers and other biomarkers
such as endothelial progenitor cells, endothelial microparticles, and ischemia
modified albumin, is just emerging. Oxidative stress has been suggested as a
pathogenic factor and therapeutic target in early stages of essential
hypertension. Systolic and diastolic blood pressure correlated positively with
plasma F2-isoprostane levels and negatively with total antioxidant capacity of
plasma in hypertensive and normotensive patients. Cardiac surgery with
extracorporeal circulation causes an ischemia/reperfusion event associated with
increased lipid peroxidation and protein carbonylation, two biomarkers associated
with oxidative damage of cardiac tissue. An enhancement of the antioxidant
defense system should contribute to ameliorating functional and structural
abnormalities derived from this metabolic impairment. However, data have to be
validated with the analysis of the appropriate oxidative stress and/or
nitrosative stress biomarkers.
PMID- 24347806
TI - A numerical method for solving a stochastic inverse problem for parameters.
AB - We review recent work (Briedt et al., 2011., 2012) on a new approach to the
formulation and solution of the stochastic inverse parameter determination
problem, i.e. determine the random variation of input parameters to a map that
matches specified random variation in the output of the map, and then apply the
various aspects of this method to the interesting Brusselator model. In this
approach, the problem is formulated as an inverse problem for an integral
equation using the Law of Total Probability. The solution method employs two
steps: (1) we construct a systematic method for approximating set-valued inverse
solutions and (2) we construct a computational approach to compute a measure
theoretic approximation of the probability measure on the input space imparted by
the approximate set-valued inverse that solves the inverse problem. In addition
to convergence analysis, we carry out an a posteriori error analysis on the
computed probability distribution that takes into account all sources of
stochastic and deterministic error.
PMID- 24347803
TI - Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated
neurological symptoms, CSD, sensitization and modulation of pain.
AB - Scientific evidence support the notion that migraine pathophysiology involves
inherited alteration of brain excitability, intracranial arterial dilatation,
recurrent activation and sensitization of the trigeminovascular pathway, and
consequential structural and functional changes in genetically susceptible
individuals. Evidence of altered brain excitability emerged from clinical and
preclinical investigation of sensory auras, ictal and interictal hypersensitivity
to visual, auditory and olfactory stimulation, and reduced activation of
descending inhibitory pain pathways. Data supporting the activation and
sensitization of the trigeminovascular system include the progressive development
of cephalic and whole-body cutaneous allodynia during a migraine attack. Also,
structural and functional alterations include the presence of subcortical white
mater lesions, thickening of cortical areas involved in processing sensory
information, and cortical neuroplastic changes induced by cortical spreading
depression. Here, we review recent anatomical data on the trigeminovascular
pathway and its activation by cortical spreading depression, a novel
understanding of the neural substrate of migraine-type photophobia, and
modulation of the trigeminovascular pathway by the brainstem, hypothalamus and
cortex.
PMID- 24347807
TI - Volatile pheromone signalling in Drosophila.
AB - Once captured by the antenna, 11-cis vaccenyl acetate (cVA) binds to an
extracellular binding protein called LUSH that undergoes a conformational shift
upon cVA binding. The stable LUSH-cVA complex is the activating ligand for
pheromone receptors present on the dendrites of the aT1 neurones, comprising the
only neurones that detect cVA pheromone. This mechanism explains the single
molecule sensitivity of insect pheromone detection systems. The receptor that
recognizes activated LUSH consists of a complex of several proteins, including
Or67d, a member of the tuning odourant receptor family, Orco, a co-receptor ion
channel, and SNMP, a CD36 homologue that may be an inhibitory subunit. In
addition, genetic screens and reconstitution experiments reveal additional
factors that are important for pheromone detection. Identification and functional
dissection of these factors in Drosophila melanogaster Meigen should permit the
identification of homologous factors in pathogenic insects and agricultural
pests, which, in turn, may be viable candidates for novel classes of compounds to
control populations of target insect species without impacting beneficial
species.
PMID- 24347808
TI - Evaluation of a Frequentist Hierarchical Model to Estimate Prevalence when
sampling from a large geographic area using Pool Screening.
AB - We present a frequentist Bernoulli-Beta hierarchical model to relax the constant
prevalence assumption underlying the traditional prevalence estimation approach
based on pooled data. This assumption is called into question when sampling from
a large geographic area. Pool screening is a method that combines individual
items into pools. Each pool will either test positive (at least one of the items
is positive) or negative (all items are negative). Pool screening is commonly
applied to the study of tropical diseases where pools consist of vectors (e.g.
black flies) that can transmit the disease. The goal is to estimate the
proportion of infected vectors. Intermediate estimators (model parameters) and
estimators of ultimate interest (pertaining to prevalence) are evaluated by
standard measures of merit, such as bias, variance and mean squared error making
extensive use of expansions. Using the hierarchical model an investigator can
determine the probability of the prevalence being below a prespecified threshold
value, a value at which no reemergence of the disease is expected. An
investigation into the least biased choice of the alpha parameter in the Beta
(alpha, beta) prevalence distribution leads to the choice of alpha = 1.
PMID- 24347809
TI - Ecosystem-scale biosphere-atmosphere interactions of a hemiboreal mixed forest
stand at Jarvselja, Estonia.
AB - During two measurement campaigns, from August to September 2008 and 2009, we
quantified the major ecosystem fluxes in a hemiboreal forest ecosystem in
Jarvselja, Estonia. The main aim of this study was to separate the ecosystem flux
components and gain insight into the performance of a multi-species multi-layered
tree stand. Carbon dioxide and water vapor fluxes were measured using the eddy
covariance method above and below the canopy in conjunction with the
microclimate. Leaf and soil contributions were quantified separately by cuvette
and chamber measurements, including fluxes of carbon dioxide, water vapor,
nitrogen oxides, nitrous oxide, methane, ozone, sulfur dioxide, and biogenic
volatile organic compounds (isoprene and monoterpenes). The latter have been as
well characterized for monoterpenes in detail. Based on measured atmospheric
trace gas concentrations, the flux tower site can be characterized as remote and
rural with low anthropogenic disturbances. Our results presented here encourage
future experimental efforts to be directed towards year round integrated
biosphere-atmosphere measurements and development of process-oriented models of
forest-atmosphere exchange taking the special case of a multi-layered and multi
species tree stand into account. As climate change likely leads to spatial
extension of hemiboreal forest ecosystems a deep understanding of the processes
and interactions therein is needed to foster management and mitigation
strategies.
PMID- 24347810
TI - A synchronized particle image velocimetry and infrared thermography technique
applied to an acoustic streaming flow.
AB - Subsurface coherent structures and surface temperatures are investigated using
simultaneous measurements of particle image velocimetry (PIV) and infrared (IR)
thermography. Results for coherent structures from acoustic streaming and
associated heating transfer in a rectangular tank with an acoustic horn mounted
horizontally at the sidewall are presented. An observed vortex pair develops and
propagates in the direction along the centerline of the horn. From the PIV
velocity field data, distinct kinematic regions are found with the Lagrangian
coherent structure (LCS) method. The implications of this analysis with respect
to heat transfer and related sonochemical applications are discussed.
PMID- 24347805
TI - The fundamental unit of pain is the cell.
AB - The molecular/genetic era has seen the discovery of a staggering number of
molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This
has stimulated pharmaceutical and biotechnology companies to invest billions of
dollars to develop drugs that enhance or inhibit the function of many these
molecules. Unfortunately this effort has provided a remarkably small return on
this investment. Inevitably, transformative progress in this field will require a
better understanding of the functional links among the ever-growing ranks of
"pain molecules," as well as their links with an even larger number of molecules
with which they interact. Importantly, all of these molecules exist side-by-side,
within a functional unit, the cell, and its adjacent matrix of extracellular
molecules. To paraphrase a recent editorial in Science magazine [223], although
we live in the Golden age of Genetics, the fundamental unit of biology is still
arguably the cell, and the cell is the critical structural and functional setting
in which the function of pain-related molecules must be understood. This review
summarizes our current understanding of the nociceptor as a cell-biological unit
that responds to a variety of extracellular inputs with a complex and highly
organized interaction of signaling molecules. We also discuss the insights that
this approach is providing into peripheral mechanisms of chronic pain and sex
dependence in pain.
PMID- 24347811
TI - Smartphone-Based, Self-Administered Intervention System for Alcohol Use
Disorders: Theory and Empirical Evidence Basis.
AB - Advances in mobile technology provide an opportunity to deliver in-the-moment
interventions to individuals with alcohol use disorders, yet availability of
effective "apps" that deliver evidence-based interventions is scarce. We
developed an immediately available, portable, smartphone-based intervention
system whose purpose is to provide stand-alone, self-administered assessment and
intervention. In this paper, we describe how theory and empirical evidence,
combined with smartphone functionality contributed to the construction of a user
friendly, engaging alcohol intervention. With translation in mind, we discuss how
we selected appropriate intervention components including assessments, feedback
and tools, that work together to produce the hypothesized outcomes.
PMID- 24347812
TI - An individual differences analysis of memory control.
AB - Performance on a wide variety of memory tasks can be hypothesized to be
influenced by processes associated with controlling the contents of memory. In
this project 328 adults ranging from 18 to 93 years of age performed six tasks
(e.g., multiple trial recall with an interpolated interference list, directed
forgetting, proactive interference, and retrieval inhibition) postulated to yield
measures of the effectiveness of memory control. Although most of the patterns
from earlier studies were replicated, only a few of the measures of memory
control were reliable at the level of individual differences. Furthermore, the
memory control measures had very weak relations with the age of the participant.
Analyses examining the relations between established cognitive abilities and
variables from the experimental tasks revealed that most of the variables were
related only to episodic memory ability.
PMID- 24347813
TI - Synonyms Provide Semantic Preview Benefit in English.
AB - While orthographic and phonological preview benefits in reading are
uncontroversial (see Schotter, Angele, & Rayner, 2012 for a review), researchers
have debated the existence of semantic preview benefit with positive evidence in
Chinese and German, but no support in English. Two experiments, using the
gazecontingent boundary paradigm (Rayner, 1975), show that semantic preview
benefit can be observed in English when the preview and target are synonyms
(share the same or highly similar meaning, e.g., curlers-rollers). However, no
semantic preview benefit was observed for semantic associates (e.g., curlers
styling). These different preview conditions represent different degrees to which
the meaning of the sentence changes when the preview is replaced by the target.
When this continuous variable (determined by a norming procedure) was used as the
predictor in the analyses, there was a significant relationship between it and
all reading time measures, suggesting that similarity in meaning between what is
accessed parafoveally and what is processed foveally may be an important
influence on the presence of semantic preview benefit. Why synonyms provide
semantic preview benefit in reading English is discussed in relation to (1)
previous failures to find semantic preview benefit in English and (2) the fact
that semantic preview benefit is observed in other languages even for non
synonymous words. Semantic preview benefit is argued to depend on several factors
attentional resources, depth of orthography, and degree of similarity between
preview and target.
PMID- 24347814
TI - Differential-associative processing or example elaboration: Which strategy is
best for learning the definitions of related and unrelated concepts?
AB - Definitions of related concepts (e.g., genotype-phenotype) are prevalent in
introductory classes. Consequently, it is important that educators and students
know which strategy(s) work best for learning them. This study showed that a new
comparative elaboration strategy, called differential-associative processing, was
better for learning definitions of related concepts than was an integrative
elaborative strategy, called example elaboration. This outcome occurred even
though example elaboration was administered in a naturalistic way (Experiment 1)
and students spent more time in the example elaboration condition learning
(Experiments 1, 2, 3), and generating pieces of information about the concepts
(Experiments 2 and 3). Further, with unrelated concepts (morpheme-fluid
intelligence), performance was similar regardless if students used differential
associative processing or example elaboration (Experiment 3). Taken as a whole,
these results suggest that differential-associative processing is better than
example elaboration for learning definitions of related concepts and is as good
as example elaboration for learning definitions of unrelated concepts.
PMID- 24347815
TI - The Quality of Toddler Child Care and Cognitive Skills at 24 Months: Propensity
Score Analysis Results from the ECLS-B.
AB - Over half of the toddlers in the U.S. experience routine nonparental care, but
much less is known about early care than about preschool care. This study
analyzed 2-year-old child care and child outcome data from the nationally
representative ECLS-B sample of children born in 2001. At two-years of age, 51%
of children experienced exclusive parental care, 18% relative care, 15% family
child care, and 16% center care. More children in nonparental care were in medium
quality care (61%) than in high quality (26%) or low quality (13%) care. Low
income children were more likely than non-low income children to be cared for by
their parents and, when in care, were more often in lower quality care. The
impact of toddler care quality on cognitive skills was estimated using propensity
score adjustments to account for potential selection confounds due to family and
child characteristics. Children's cognitive scores were higher in high or medium
quality care than in low quality care, but no evidence emerged suggesting that
poverty moderated the quality effects. Nevertheless, this suggests that
increasing the proportion of low-income children in high quality care could
reduce the achievement gap because low-income children are very unlikely to
experience high quality care.
PMID- 24347816
TI - WHEN DOES IMPROVING HEALTH RAISE GDP?
AB - We assess quantitatively the effect of exogenous health improvements on output
per capita. Our simulation model allows for a direct effect of health on worker
productivity, as well as indirect effects that run through schooling, the size
and age-structure of the population, capital accumulation, and crowding of fixed
natural resources. The model is parameterized using a combination of
microeconomic estimates, data on demographics, disease burdens, and natural
resource income in developing countries, and standard components of quantitative
macroeconomic theory. We consider both changes in general health, proxied by
improvements in life expectancy, and changes in the prevalence of two particular
diseases: malaria and tuberculosis. We find that the effects of health
improvements on income per capita are substantially lower than those that are
often quoted by policy-makers, and may not emerge at all for three decades or
more after the initial improvement in health. The results suggest that proponents
of efforts to improve health in developing countries should rely on humanitarian
rather than economic arguments.
PMID- 24347817
TI - Evidence for a Syndemic in Aging HIV-positive Gay, Bisexual, and Other MSM:
Implications for a Holistic Approach to Prevention and Healthcare.
AB - The theory of syndemics has been widely applied in HIV prevention studies of gay,
bisexual, and other MSM over the last decade. Our investigation is the first to
consider the applicability of the theory in a sample of aging (ages 50 and over)
HIV-positive MSM, which is a growing population in the United States. A sample of
199 men were actively recruited and assessed in terms of mental health and drug
use burden, as well as sexual risk behaviors. Bivariate and multivariable
analyses indicate a high level of association between psychosocial burdens (i.e.,
drug use and mental health) and same-sex unprotected sexual behaviors, providing
initial support for the applicability of the theory of syndemics to this
population. Further support can be seen in participants' narratives. Findings
suggest the mutually reinforcing nature of drug use, psychiatric disorders, and
unprotected sexual behavior in older, HIV-positive, gay, bisexual, and other MSM,
highlighting the need for holistic strategies to prevention and care among this
population of older and sexually active individuals. In short, the generation of
gay men who came of age in the late 1970s and 1980s, "the AIDS Generation," are
continuing to mature such that further efforts must be enacted to meet the
multidimensional nature of these men's physical, mental, and sexual health needs.
PMID- 24347818
TI - MORE AND LESS THAN EQUAL: How Men Factor in the Reproductive Equation.
AB - In both social science and medicine, research on reproduction generally focuses
on women. In this article, we examine how men's reproductive contributions are
understood. We develop an analytic framework that brings together Cynthia
Daniels' conceptualization of reproductive masculinity (2006) with a staged view
of reproduction, where the stages include the period before conception,
conception, gestation, and birth. Drawing on data from two medical sites that are
oriented to the period before pregnancy (preconception health care and sperm
banks), we examine how gendered knowledge about reproduction produces different
reproductive equations in different stages of the reproductive process. We
conclude with a new research agenda that emerges from rethinking the role of men
and masculinity in reproduction.
PMID- 24347819
TI - Singing in the face of death: male banded wrens sing more to playback in their
last breeding season.
AB - Investment in signalling is subject to multiple trade-offs that vary with life
stage, leading to a complex relationship between survival and trait expression.
We show a negative relationship between survival and song rate in response to
simulated territorial intrusion in male banded wrens (Thryophilus pleurostictus),
and test several explanations for this association. (1) Male age failed to
explain the association: though age affected song rate in a cross-sectional
analysis, longitudinal analysis showed that individuals did not increase their
song rate as they got older. Reconciling these results suggests differential
selection against young males that respond to intrusion with low song rates. (2)
Mortality costs of high song rates did not appear to explain the negative
relationship between song rate and survival because, though song rate in response
to playback was condition-dependent, high song rates in a different context did
not appear to impose mortality costs. (3) High levels of territorial pressure may
have increased mortality, but were not associated with high song rates in
response to playback. (4) Since song rates did not increase with age, but tended
to increase only in the last year of life, we tentatively suggest that the
negative relationship between song rate and survival could represent a terminal
investment in territorial defence by males in their final breeding season, though
further work is needed to confirm this conclusion.
PMID- 24347820
TI - Quasi-balanced two-wave mixing interferometer for remote ultrasound detection.
AB - We present an improved detection scheme for a two-wave mixing interferometer with
a Bi12SiO20 crystal. The proposed detection scheme allows quasi-balanced
detection of ultrasonic signals whereby electrical disturbances are suppressed.
Quasi-balancing is achieved by changing the polarity of the high voltage at the
photorefractive crystal, leading to an inversion of the optical interference
signal, in combination with inversion of the detector signal using a signal
inverter before the data acquisition device. The polarity of the high voltage is
changed by utilizing an H-bridge consisting of five high-voltage relays.
Microcontrollers are used to synchronize the reversion of the high voltage at the
photorefractive crystal and the inversion of the measured signals. We demonstrate
remote measurement of ultrasonic waves and shown that electrical disturbances are
suppressed using the quasi-balanced mode.
PMID- 24347821
TI - Circulating C19MC microRNAs in preeclampsia, gestational hypertension, and fetal
growth restriction.
AB - The objective of the study was to identify the profile of circulating C19MC
microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR
526a) in patients with established preeclampsia (n = 63), fetal growth
restriction (n = 27), and gestational hypertension (n = 23). We examined the
correlation between plasmatic concentrations and expression levels of microRNAs
and the severity of the disease with respect to clinical signs, requirements for
the delivery, and Doppler ultrasound parameters. Using absolute and relative
quantification approaches, increased extracellular C19MC microRNA levels (miR-516
5p, P = 0.037, P = 0.009; miR-517*, P = 0.033, P = 0.043; miR-520a*, P = 0.001, P
= 0.009; miR-525, P = 0.026, P = 0.01; miR-526a, P = 0.03, P = 0.035) were
detected in patients with preeclampsia. The association analysis pointed to no
relationship between C19MC microRNA plasmatic concentrations and expression
profile and identified risk factors for a poorer perinatal outcome. However, the
dependence between the levels of plasmatic C19MC microRNAs and the pulsatility
index in the middle cerebral artery and the values of cerebroplacental ratio was
demonstrated. The study brought the interesting finding that the upregulation of
miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic
phenomenon of established preeclampsia.
PMID- 24347822
TI - Dose-dependent anti-inflammatory and neuroprotective effects of an alphanubeta3
integrin-binding peptide.
AB - Previous studies have shown that prevention of leukocyte infiltration by
targeting integrins involved in transendothelial migration may suppress the
clinical and pathological features of neuroinflammatory disease. This study was
designed to investigate the effects of C16, an alphanubeta3 integrin-binding
peptide, in an acute experimental allergic encephalomyelitis (EAE) rat model.
Multiple histological and immunohistochemical staining, electron microscopy
observation, ELISA assay, Western blot, and magnetic resonance imaging (MRI) were
employed to assess the degree of inflammation, axonal loss, neuronal apoptosis,
white matter demyelination, and extent of gliosis in the brain and spinal cord of
differently treated EAE models. The results showed that C16 treatment could
inhibit extensive leukocyte and macrophage accumulation and infiltration and
reduce cytokine tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
gamma) expression levels. A significantly lower clinical score at the peak time
of disease was also demonstrated in the C16 treated group. Moreover,
astrogliosis, demyelination, neuronal death, and axonal loss were all alleviated
in C16 treated EAE animals, which may be attributed to the improvement of
microenvironment. The data suggests that C16 peptide may act as a protective
agent by attenuating inflammatory progression and thus affecting the expression
of some proinflammatory cytokines during neuroinflammatory disease.
PMID- 24347823
TI - Plasma levels of IL-17, VEGF, and adrenomedullin and S-cone dysfunction of the
retina in children and adolescents without signs of retinopathy and with varied
duration of diabetes.
AB - The study objective was to assess chosen biochemical parameters of blood and
bioelectric function of the retina in patients with T1DM. The study group
consisted of 41 patients with T1DM with no signs of diabetic retinopathy. The
control group included 21 pediatric patients. We performed (1) S-cone ERG testing
with retina response stimulation in both eyes at the luminance of 0.1, 0.2, and
0.5 (cd * s/m(2)) with the 440 nm blue flash and light application of the amber
background (300 ph cd/m(2), 495 nm wavelength), (2) anthropometric measurements,
(3) biochemical investigations: IL-17, VEGF, and ADM by the ELISA method. A
comparison of the ERG results with biochemical investigations indicates a likely
correlation between the worsening of retinal bioelectric function and VEGF levels
growing with diabetes duration. We showed a negative correlation between ADM and
HbA1c and described possible causes of ADM reduction observed in subgroup I. We
demonstrated the presence of bioelectric retinal dysfunction already before the
diagnosis of diabetic retinopathy, which provides new possibilities in the
diagnosis of preclinical chronic complications of diabetes. The changes observed
in the levels of IL-17, ADM, and VEGF suggest their involvement in the diabetic
pathogenesis of eye diseases.
PMID- 24347824
TI - Heat shock proteins 60 and 70 specific proinflammatory and cytotoxic response of
CD4+CD28null cells in chronic kidney disease.
AB - BACKGROUND: CD4(+)CD28(null) T cells are expanded in peripheral blood of patients
with chronic kidney disease and associated with subclinical atherosclerosis.
However, triggers for the oligoclonal expansion and activation of these cells are
not clear. METHODS: We investigated twenty-five stage V-IV chronic kidney disease
(CKD) patients and eight healthy subjects (HC). Peripheral mononuclear cells were
isolated and incubated with heat shock protein- (HSP) 60 and 70. CD4(+)CD28(null)
and CD4(+)CD28(+) cells were sorted by flowcytometry and antigen specific
response was assessed by the mRNA and protein expression of interferon (IFN)
gamma, perforin, and granzyme B using qRT-PCR and Elispot. RESULTS: The basal
mRNA expression of IFN-gamma, perforin, and granzyme B in CD4(+)CD28(null) cells
was higher in subjects with CKD compared to that in HC (P < 0.0001). Subjects
with CKD also showed expression of IFN-gamma, perforin, and granzyme B in the
CD4(+)CD28(+) subset, but this was much weaker than that seen in the
CD4(+)CD28(null) population (P < 0.0001). We did not note the expression of these
molecules at mRNA or protein level in either subset of CD4 cells in HC. After
incubation with HSP60 and HSP70, CD4(+)CD28(null) cells showed increased
expression at mRNA (P < 0.001) and protein level (P < 0.001). CD4(+)CD28(+) cells
also showed a weak increase in expression. No antigen-specific response was noted
in HC. CONCLUSION: These data show that CD4(+)CD28(null) cells in subjects with
CKD react with HSP60 and HSP70 by upregulating the expression of IFN-gamma,
perforin and granzyme B. Increased circulating level of HSP60 and HSP70 might
play a role in initiation and/or progression of atherosclerosis in CKD subjects
through perturbation of CD4(+)CD28(null) cells.
PMID- 24347825
TI - Body mass index: a risk factor for retinopathy in type 2 diabetic patients.
AB - The aim of the study was to investigate whether body mass index (BMI)
independently or in correlation with other risk factors is associated with
diabetic retinopathy (DR) progression. The study included 545 patients with type
2 diabetes. According to DR status, they were divided into three groups: group 1
(no retinopathy; n = 296), group 2 (mild/moderate nonproliferative DR; n = 118),
and group 3 (severe/very severe NPDR or proliferative DR; n = 131). Patients
without DR were younger than those with signs of retinopathy at time of diabetes
onset whilst diabetes duration was longer in groups with severe NPDR and PDR. DR
progression was correlated with diabetes duration, BMI, HbA1c, hypertension, and
cholesterol. Statistical analyses showed that the progression of retinopathy
increased significantly with higher BMI (gr. 1: 26.50 +/- 2.70, gr. 2: 28.11 +/-
3.00, gr. 3: 28.69 +/- 2.50; P < 0.01). We observed a significant deterioration
of HbA1c and a significant increase in cholesterol and hypertension with an
increase in BMI. Correlation between BMI and triglycerides was not significant.
Thus, BMI in correlation with HbA1c cholesterol and hypertension appears to be
associated with the progression of DR in type 2 diabetes and may serve as a
predictive factor for the development of this important cause of visual loss in
developed countries.
PMID- 24347827
TI - NF-kappaB inhibition after cecal ligation and puncture reduces sepsis-associated
lung injury without altering bacterial host defense.
AB - INTRODUCTION: Since the NF-kappaB pathway regulates both inflammation and host
defense, it is uncertain whether interventions targeting NF-kappaB would be
beneficial in sepsis. Based on the kinetics of the innate immune response, we
postulated that selective NF-kappaB inhibition during a defined time period after
the onset of sepsis would reduce acute lung injury without compromising bacterial
host defense. METHODS: Mice underwent cecal ligation and puncture (CLP). An NF
kappaB inhibitor, BMS-345541 (50 ug/g mice), was administered by peroral gavage
beginning 2 hours after CLP and repeated at 6 hour intervals for 2 additional
doses. RESULTS: Mice treated with BMS-345541 after CLP showed reduced
neutrophilic alveolitis and lower levels of KC in bronchoalveolar lavage fluid
compared to mice treated with CLP+vehicle. In addition, mice treated with CLP+BMS
had minimal histological evidence of lung injury and normal wet-dry ratios,
indicating protection from acute lung injury. Treatment with the NF-kappaB
inhibitor did not affect the ability of cultured macrophages to phagocytose
bacteria and did not alter bacterial colony counts in blood, lung tissue, or
peritoneal fluid at 24 hours after CLP. While BMS-345541 treatment did not alter
mortality after CLP, our results showed a trend towards improved survival.
CONCLUSION: Transiently blocking NF-kappaB activity after the onset of CLP
induced sepsis can effectively reduce acute lung injury in mice without
compromising bacterial host defense or survival after CLP.
PMID- 24347826
TI - Hyperoxia exacerbates postnatal inflammation-induced lung injury in neonatal BRP
39 null mutant mice promoting the M1 macrophage phenotype.
AB - RATIONALE: Hyperoxia exposure to developing lungs-critical in the pathogenesis of
bronchopulmonary dysplasia-may augment lung inflammation by inhibiting anti
inflammatory mediators in alveolar macrophages. OBJECTIVE: We sought to determine
the O2-induced effects on the polarization of macrophages and the role of anti
inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. METHODS: We
used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization
(M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39(-/-) mice
received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal
(PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered
on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL)
cell counts, BAL protein, and cytokines measurements were performed. MEASUREMENTS
AND MAIN RESULTS: Hyperoxia differentially contributed to macrophage polarization
by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype.
BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1
phenotype. In addition, BRP-39(-/-) mice were significantly more sensitive to LPS
plus hyperoxia induced lung injury and mortality compared to WT mice.
CONCLUSIONS: These findings collectively indicate that BRP-39 is involved in
repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating
inflammatory responses in macrophages and preventing neonatal lung injury.
PMID- 24347828
TI - Poly (ADP-ribose) polymerase mediates diabetes-induced retinal neuropathy.
AB - Retinal neuropathy is an early event in the development of diabetic retinopathy.
One of the potential enzymes that are activated by oxidative stress in the
diabetic retina is poly (ADP-ribose) polymerase (PARP). We investigated the
effect of the PARP inhibitor 1,5-isoquinolinediol on the expression of the
neurodegeneration mediators and markers in the retinas of diabetic rats. After
two weeks of streptozotocin-induced diabetes, rats were treated with 1,5
isoquinolinediol (3 mg/kg/day). After 4 weeks of diabetes, the retinas were
harvested and the levels of reactive oxygen species (ROS) were determined
fluorometrically and the expressions of PARP, phosporylated-ERK1/2, BDNF,
synaptophysin, glutamine synthetase (GS), and caspase-3 were determined by
Western blot analysis. Retinal levels of ROS, PARP-1/2, phosphorylated ERK1/2,
and cleaved caspase-3 were significantly increased, whereas the expressions of
BDNF synaptophysin and GS were significantly decreased in the retinas of diabetic
rats, compared to nondiabetic rats. Administration of 1,5-isoquinolinediol did
not affect the metabolic status of the diabetic rats, but it significantly
attenuated diabetes-induced upregulation of PARP, ROS, ERK1/2 phosphorylation,
and cleaved caspase-3 and downregulation of BDNF, synaptophysin, and GS. These
findings suggest a beneficial effect of the PARP inhibitor in increasing
neurotrophic support and ameliorating early retinal neuropathy induced by
diabetes.
PMID- 24347829
TI - Systemic treatments for noninfectious vitreous inflammation.
AB - Vitreous inflammation, or vitritis, may result from many causes, including both
infectious and noninfectious, including rheumatologic and autoimmune processes.
Vitritis is commonly vision threatening and has serious sequelae. Treatment is
frequently challenging, but, today, there are multiple methods of systemic
treatment for vitritis. These categories include corticosteroids,
antimetabolites, alkylating agents, T-cell inhibitors/calcineurin inhibitors, and
biologic agents. These treatment categories were reviewed last year, but, even
over the course of just a year, many therapies have made progress, as we have
learned more about their indications and efficacy. We discuss here discoveries
made over the past year on both existing and new drugs, as well as reviewing
mechanisms of action, clinical dosages, specific conditions that are treated,
adverse effects, and usual course of treatment for each class of therapy.
PMID- 24347830
TI - Myeloperoxidase-dependent LDL modifications in bloodstream are mainly predicted
by angiotensin II, adiponectin, and myeloperoxidase activity: a cross-sectional
study in men.
AB - The present paradigm of atherogenesis proposes that low density lipoproteins
(LDLs) are trapped in subendothelial space of the vascular wall where they are
oxidized. Previously, we showed that oxidation is not restricted to the
subendothelial location. Myeloperoxidase (MPO), an enzyme secreted by neutrophils
and macrophages, can modify LDL (Mox-LDL) at the surface of endothelial cells. In
addition we observed that the activation of the endothelial cells by angiotensin
II amplifies this process. We suggested that induction of the NADPH oxidase
complex was a major step in the oxidative process. Based on these data, we asked
whether there was an independent association, in 121 patients, between NADPH
oxidase modulators, such as angiotensin II, adiponectin, and levels of
circulating Mox-LDL. Our observations suggest that the combination of blood
angiotensin II, MPO activity, and adiponectin explains, at least partially, serum
Mox-LDL levels.
PMID- 24347832
TI - Oxidized LDL in inflammation: from bench to bedside.
PMID- 24347831
TI - Follistatin-like 1: a potential mediator of inflammation in obesity.
AB - Obesity is associated with a state of chronic low-grade inflammation, which
contributes to insulin resistance and type 2 diabetes. However, the molecular
mechanisms that link obesity to inflammation are not fully understood.
Follistatin-like 1 (FSTL1) is a novel proinflammatory cytokine that is expressed
in adipose tissue and secreted by preadipocytes/adipocytes. We aimed to test
whether FSTL1 could have a role in obesity-induced inflammation and insulin
resistance. It was found that FSTL1 expression was markedly decreased during
differentiation of 3T3-L1 preadipocytes but reinduced by TNF-alpha. Furthermore,
a significant increase in FSTL1 levels was observed in adipose tissue of obese
ob/ob mice, as well as in serum of overweight/obese subjects. Mechanistic studies
revealed that FSTL1 induced inflammatory responses in both 3T3-L1 adipocytes and
RAW264.7 macrophages. The expression of proinflammatory mediators including IL-6,
TNF-alpha, and MCP-1 was upregulated by recombinant FSTL1 in a dose-dependent
manner, paralleled with activation of the IKKbeta-NFkappaB and JNK signaling
pathways in the two cell lines. Moreover, FSTL1 impaired insulin signaling in 3T3
L1 adipocytes, as revealed by attenuated phosphorylation of both Akt and IRS-1 in
response to insulin stimulation. Together, our results suggest that FSTL1 is a
potential mediator of inflammation and insulin resistance in obesity.
PMID- 24347833
TI - A possible role for CD8+ T lymphocytes in the cell-mediated pathogenesis of
pemphigus vulgaris.
AB - Pemphigus vulgaris (PV) is an autoimmune blistering disease whose pathogenesis
involves both humoral and cell-mediated immune response. Though the pathogenetic
role of autoantibodies directed against desmoglein 3 is certain, a number of
other factors have been suggested to determine acantholysis in PV. In this study
we examined the possible role of CD8+ T cells in the development of acantholysis
by a passive transfer of PV autoantibodies using CD8 deficient mice, and we also
studied the inflammatory infiltrate of PV skin lesions by immunohistochemical
staining. The results of the immunohistochemical staining to study the expression
of CD3, CD4, and CD8 in PV skin lesions showed that CD4+ are more expressed than
CD8+ in the inflammatory infiltrate of PV lesions, confirming the data of the
previous literature. The passive transfer study showed a lower incidence of
pemphigus in the group of CD8 deficient mice compared to the control one of wild
type mice. These results suggest that CD8+ T cells may play a role in the
pathogenesis of PV, perhaps through the Fas/FasL pathway.
PMID- 24347834
TI - Mediators of inflammation as targets for chronic pain treatment.
PMID- 24347835
TI - Insulin therapy with personal insulin pumps and early angiopathy in children with
type 1 diabetes mellitus.
AB - OBJECTIVE: Assessment of the effect of a treatment method change from multiple
daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII)
on the development of early angiopathy in children with T1DM with or without
retinopathy. METHODS: The study pump group involved 32 diabetic children aged
14.8, with the initial HbA1c level of 8.3%, previously treated by MDI. The
patients were examined before pump insertion and after 3 and 6 months of CSII. We
assessed HbA1c level, carotid artery intima-media thickness (c-IMT), and flow
mediated dilatation (FMD) of the brachial artery. The pump group was compared to
a group of eight teenagers with diagnosed nonproliferative retinopathy, treated
with MDI. RESULTS: HbA1c in the entire group was found to improve in the second
and in the third examination. During 6 months of CSII, FMD increased and IMT
decreased. Retinopathic adolescents had significantly thicker IMT and lower FMD
compared to baseline results of the pump group. Treatment intensification in the
retinopathy-free children enhanced these differences. CONCLUSIONS: CSII is
associated with lower IMT and higher FMD. Whether on the long-run CSII is
superior to MDI to delay the occurrence of diabetes late complications remains to
be explained.
PMID- 24347836
TI - Histopathological implications of Aspergillus infection in lung.
AB - This paper opens with a discussion on the significance of invasive fungal
infections in advanced contemporary medicine, with an emphasis on the
intractability of disease management and the difficulties of diagnosis. This is
followed by a discussion concerning classification, histopathological features,
and pathophysiology. While it has been largely accepted that Aspergillus species
is recognized by cellular receptors and attacked by neutrophils, the radiological
and macroscopic findings linking infection with neutropenia remain unconfirmed.
In an effort to gain a better understanding of the pathophysiology and
pathogenesis of invasive aspergillosis, we wish to emphasize the utility of
radiological and histopathological examinations since these can provide detailed
information on the extremely complex interaction between the causative microbes
and tissue responses. A review of noninvasive or semi-invasive aspergillosis is
also provided, with particular emphasis on chronic necrotizing pulmonary
aspergillosis, which is recognized as a transition form of simple pulmonary
aspergilloma and invasive pulmonary aspergillosis, although few findings have
been reported in this area.
PMID- 24347837
TI - E. coli endotoxin modulates the expression of Sirtuin proteins in PBMC in humans.
AB - BACKGROUND: Sirtuin (SIRT) proteins are class I histone deacetylases displaying
gene regulatory functions in inflammatory, cancer, and metabolic diseases. These
SIRT actions involve the nuclear factor kappa B and its inhibitor I kappa B
pathway. However, the regulation of SIRT in vivo is still unclear. MATERIAL AND
METHODS: In a human endotoxemia model, 20 healthy male subjects received an
intravenous bolus of 2 ng/kg body weight Escherichia coli endotoxin (LPS). SIRT
expression was investigated in peripheral blood mononuclear cells (PBMC) with
qPCR and Western blot before and 3 hours, 6 hours, and 24 hours after LPS
challenge. Additionally, SIRT regulation was studied in vitro in cultivated PBMC
after incubation with 20 ng/mL LPS. RESULTS: A downregulation by >40% of SIRT1
mRNA was detectable 3 hours after LPS and of SIRT3 mRNA 6 hours after LPS. SIRT3,
IkappaBalpha, and IkappaB-beta protein expressions were decreased 3 and 6 hours
after LPS. SIRT2 mRNA or protein expression did not change following LPS. These
findings were consistent in vitro and associated with augmented phosphorylation
of IkappaB-beta. DISCUSSION: In this E. coli endotoxemia model, SIRT1 and SIRT3
mRNA expressions in PBMC in humans were reduced after LPS challenge. This
suggests that SIRT may represent an inflammatory target protein in vivo.
PMID- 24347838
TI - Clearance of apoptotic cells by macrophages induces regulatory phenotype and
involves stimulation of CD36 and platelet-activating factor receptor.
AB - Phagocytosis of apoptotic cells (efferocytosis) induces macrophage
differentiation towards a regulatory phenotype (IL-10(high)/IL-12p40(low)). CD36
is involved in the recognition of apoptotic cells (AC), and we have shown that
the platelet-activating factor receptor (PAFR) is also involved. Here, we
investigated the contribution of PAFR and CD36 to efferocytosis and to the
establishment of a regulatory macrophage phenotype. Mice bone marrow-derived
macrophages were cocultured with apoptotic thymocytes, and the phagocytic index
was determined. Blockage of PAFR with antagonists or CD36 with specific
antibodies inhibited the phagocytosis of AC (~70-80%). Using immunoprecipitation
and confocal microscopy, we showed that efferocytosis increased the CD36 and PAFR
colocalisation in the macrophage plasma membrane; PAFR and CD36
coimmunoprecipitated with flotillin-1, a constitutive lipid raft protein, and
disruption of these membrane microdomains by methyl-beta-cyclodextrin reduced AC
phagocytosis. Efferocytosis induced a pattern of cytokine production, IL
10(high)/IL-12p40(low), that is, characteristic of a regulatory phenotype. LPS
potentiated the efferocytosis-induced production of IL-10, and this was prevented
by blocking PAFR or CD36. It can be concluded that phagocytosis of apoptotic
cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for
optimal efferocytosis and the establishment of the macrophage regulatory
phenotype.
PMID- 24347840
TI - Message from the president, Indian chest society.
PMID- 24347839
TI - Sample size estimation for alternating logistic regressions analysis of
multilevel randomized community trials of under-age drinking.
AB - Under-age drinking is an enormous public health issue in the USA. Evidence that
community level structures may impact on under-age drinking has led to a
proliferation of efforts to change the environment surrounding the use of
alcohol. Although the focus of these efforts is to reduce drinking by individual
youths, environmental interventions are typically implemented at the community
level with entire communities randomized to the same intervention condition. A
distinct feature of these trials is the tendency of the behaviours of individuals
residing in the same community to be more alike than that of others residing in
different communities, which is herein called 'clustering'. Statistical analyses
and sample size calculations must account for this clustering to avoid type I
errors and to ensure an appropriately powered trial. Clustering itself may also
be of scientific interest. We consider the alternating logistic regressions
procedure within the population-averaged modelling framework to estimate the
effect of a law enforcement intervention on the prevalence of under-age drinking
behaviours while modelling the clustering at multiple levels, e.g. within
communities and within neighbourhoods nested within communities, by using
pairwise odds ratios. We then derive sample size formulae for estimating
intervention effects when planning a post-test-only or repeated cross-sectional
community-randomized trial using the alternating logistic regressions procedure.
PMID- 24347841
TI - Message from the hon. Secretary, Indian chest society.
PMID- 24347842
TI - From the Editor's Desk.
PMID- 24347843
TI - Voicing the natural way.
PMID- 24347844
TI - Voice recognition is here comma like it or not period.
AB - Voice recognition (VR) technology needs improvement, but is as integral to the
current practice of radiology as Radiology Information Systems and Picture
Archival and Communication Systems. In the 1990s, the radiology community gave VR
technology a rather lukewarm reception, but since then it has emerged as the
predominant method of radiology reporting in the United States. In this article,
we examine how VR technology works, outline the positive and negative aspects of
VR technology on work flow, identify common VR transcription errors and review
the discussion on VR adoption in the recent literature. We add to the discussion
our personal experiences in an international teleradiology group.
PMID- 24347845
TI - MRI brain in monohalomethane toxic encephalopathy: A case report.
AB - Monohalomethanes are alkylating agents that have been used as methylating agents,
laboratory reagents, refrigerants, aerosol propellants, pesticides, fumigants,
fire-extinguishing agents, anesthetics, degreasers, blowing agents for plastic
foams, and chemical intermediates. Compounds in this group are methyl chloride,
methyl bromide, methyl iodide (MI), and methyl fluoride. MI is a colorless
volatile liquid used as a methylating agent to manufacture a few pharmaceuticals
and is also used as a fumigative insecticide. It is a rare intoxicant.
Neurotoxicity is known with both acute and chronic exposure to MI. We present the
characteristic magnetic resonance imaging (MRI) brain findings in a patient who
developed neuropsychiatric symptoms weeks after occupational exposure to
excessive doses of MI.
PMID- 24347846
TI - Call-Fleming syndrome.
AB - Call-Fleming syndrome is a part of reversible cerebral vasoconstriction syndrome
(RCVS) group and is thought to be of idiopathic origin. It is classically
described to be having multisegmental, focal vasospasms in the cerebral arteries.
It is characterized clinically by the sudden onset of severe headache,
classically described as thunderclap headache, with or without associated
neurological deficits. The importance of it lies in that it is a potentially
reversible cause of this clinical presentation, unlike its other counterparts,
aneurysmal subarachnoid hemorrhage (SAH) or vasculitis.
PMID- 24347847
TI - Cavernous hemangioma located at the foramen of Monro: Radiopathological
correlation.
AB - Intraventricular cavernous hemangiomas are rare. Amongst them, cavernomas located
at the foramen of Monro are of greater interest because of their rare location,
varied symptoms, and often association with hydrocephalus. We present a rare case
of cavernous hemangioma located at foramen of Monro, with its radiopathological
confirmation.
PMID- 24347848
TI - Herniation of spinal cord into nerve root avulsion pseudomeningocele: A rare
cause of delayed progressive neurological deficit.
AB - We present a patient with old traumatic right brachial plexus injury, who
developed progressive neurological deterioration 4 years after the initial
injury. On magnetic resonance imaging (MRI), herniation of the upper dorsal cord
was noted into a post-traumatic pseudomeningocele. Though the herniation of cord
into a post-traumatic pseudomeningocele is very rare, it should be suspected in
cases of delayed progressive myelopathy. A three dimensional (3-D) T2-weighted
sequence such as Sampling Perfection with Application optimized Contrasts using
different flip angle Evolution (SPACE) or constructive interference in steady
state (CISS) provides optimal visualization of the herniated cord and helps in
surgical planning.
PMID- 24347849
TI - Pseudoaneurysm of internal carotid artery after carotid body tumor excision.
AB - The common causes of pseudoaneurysms of internal carotid artery (ICA) in the neck
are penetrating trauma, head and neck surgeries, carotid endarterectomies,
infiltrating metastatic lymph nodes and neoplasms. We report a young male patient
who presented with a swelling in left upper neck diagnosed as carotid body tumor
with ultrasonography and magnetic resonance imaging. Subadventitial excision of
the tumor was done. The patient developed dense right hemiplegia in the immediate
postoperative period. Doppler study of neck revealed left ICA dissection with
partial thrombosis of the lumen. Computed tomography of the brain revealed
nonhemorrhagic left capsuloganglionic infarct and he was managed conservatively
with heparin. Follow-up Doppler study done 2 weeks later revealed pseudoaneurysm
of the ICA. Attempts to obliterate the pseudoaneurysm by interventional
procedures failed due to the narrow neck of the pseudoaneurysm. Heparin was
stopped and patient was maintained only on oral aspirin. Doppler study repeated 1
week later showed spontaneous thrombosis of the pseudoaneurysm with good flow in
the distal ICA. To the best of our knowledge, only one case of pseudo
pseudoaneurysm complicating surgical resection of carotid body tumor has been
reported so far The etiology, imaging features, and treatment options of
pseudoaneurysms are discussed.
PMID- 24347850
TI - Imaging features of rhinosporidiosis on contrast CT.
AB - CONTEXT: Rhinosporidiosis is a chronic granulomatous disease endemic in certain
regions of India. Computed tomography (CT) imaging appearances of
rhinosporidiosis have not been previously described in the literature. AIMS: To
study imaging features in rhinosporidiosis with contrast-enhanced CT and
elucidate its role in the evaluation of this disease. MATERIALS AND METHODS:
Sixteen patients with pathologically proven rhinosporidiosis were included in the
study. Contrast-enhanced CT images were analyzed retrospectively and imaging
findings were correlated with surgical and histopathologic findings. RESULTS: A
total of 29 lesions were found and evaluated. On contrast-enhanced CT,
rhinosporidiosis was seen as moderately enhancing lobulated or irregular soft
tissue mass lesions in the nasal cavity (n = 13), lesions arising in nasal cavity
and extending through choana into nasopharynx (n = 5), pedunculated polypoidal
lesions arising from the nasopharyngeal wall (n = 5), oropharyngeal wall (n = 2),
larynx (n = 1), bronchus (n = 1), skin and subcutaneous tissue (n = 2). The
inferior nasal cavity comprising nasal floor, inferior turbinate, and inferior
meatus was the most common site of involvement (n = 13). Surrounding bone
involvement was seen in the form of rarefaction (n = 6), partial (n = 3) or
complete erosion (n = 3) of inferior turbinate, thinning of medial maxillary wall
(n = 2), and septal erosion (n = 2). Nasolacrimal duct involvement was seen in
four cases. CONCLUSIONS: Contrast-enhanced CT has an important role in
delineating the site and extent of the disease, as well as the involvement of
surrounding bone, nasolacrimal duct and tracheobronchial tree. This provides a
useful roadmap prior to surgery.
PMID- 24347851
TI - Role of dual-energy contrast-enhanced digital mammography as a problem-solving
tool in dense breasts: A case report.
AB - Breast density is strongly and independently related to the risk of breast
cancer. Women with very dense breasts may have up to five times higher chances of
developing malignancy as compared to those with less breast density. Detecting
lesions in extremely dense or heterogeneous breasts on screening mammogram can be
difficult. We report a case of incidental bilateral breast malignancy in an
asymptomatic patient in whom mammogram and screening ultrasound were equivocal.
PMID- 24347852
TI - Variations of celiac axis, common hepatic artery and its branches in 600
patients.
AB - PURPOSE: To evaluate the spectrum of celiac axis, common hepatic artery (CHA),
right, left, middle hepatic artery and gastroduodenal artery variations by using
spiral computed tomography (CT). MATERIALS AND METHODS: A retrospective review of
Multidetector CT (MDCT) abdominal angiography scans was performed in patients
sent for various liver and other abdominal pathologies between January 2012 and
February 2013. A total of 600 patients were evaluated. Definitions of CHA,
ambiguous celiac axis, course and division patterns of CHA, replaced hepatic
artery, accessory hepatic artery and middle hepatic artery were used as proposed
by Song et al., Covey et al., and Wang et al. The pattern of the aortic origin of
branches of celiac axis, common hepatic artery and its branches was analyzed.
RESULTS: Six types of celiac axis anatomic variations were identified in our
study. A total of 546 of the 600 patients had a normal celiac axis anatomy.
Anatomic variations were seen in 5.5% of patients. Ambiguous anatomy was seen in
3.5% of the patients. CHA originated from celiac axis in 95.83% of the patients.
Variations in anatomic origin of CHA were seen in 8 patients. Ambiguous dual
pathway was seen in 4 patients. Normal Sp-preportal course of CHA was identified
in 97.78% of cases, Sp-retroportal course in 7 patients, Tp-preportal course in
2, Tp-retroportal in 1, Ip-preportal in 1 and through Ligamentum venosum in 2
patients. Normal origin of RHA from HAP was seen in 79.6% patients. Replaced
origin of RHA was seen in 15.16% cases and Accessory origin of RHA was seen in
5.16% cases. LHA originated from HAP in 81.5% patients. Replaced LHA origin was
seen in 10.8% cases and Accessory LHA origin seen in 7.6% cases. MHA originated
from RHA in 41.3% patients, LHA in 27.83% and from CHA in 4.5% cases. Origin of
MHA could not be defined in 26.3% of patients. GDA originated from CHA in 97.6%
of patients, from celiac axis in 1.6%, from RHA in 0.33% in patients.
Trifurcation of CHA was seen in 7.16% and quadrifurcation of CHA in 2.16%.
CONCLUSION: CT Angiography is a safe and highly sensitive and accurate modality
for evaluation of arterial anatomy and its variants.
PMID- 24347853
TI - CT imaging findings and endovascular management of isolated spontaneous
dissecting aneurysm of celiac artery.
AB - Isolated spontaneous dissecting aneurysm of celiac artery without concomitant
involvement of aorta is a rare entity and only a few cases are reported in the
literature. More cases are being detected recently with greater advancements in
CT technology. Clinicians and emergency physicians should be aware of this
condition and should include it in the differential diagnosis of patients who
present with refractory postprandial epigastric pain, particularly in middle-aged
men. We present a case of a 45-year-old male with isolated spontaneous dissecting
celiac artery aneurysm, with special emphasis on CT findings and the role of
endovascular management.
PMID- 24347854
TI - Extrahepatic biliary atresia with choledochal cyst: Prenatal MRI predicted and
post natally confirmed: A case report.
AB - Extrahepatic biliary atresia (EHBA) is an uncommon cause of neonatal jaundice.
Antenatal Magnetic Resonance Imaging (MRI) diagnosis of EHBA has not been
published to the best of our knowledge till date. EHBA with cystic component is
likely to be mistaken for choledochal cyst. A case that was antenatally predicted
and postnatally confirmed by surgery and histopathology is being reported. All
imaging signs are analyzed herewith. Imaging helps in the prediction of EHBA and
also helps in early postnatal surgical referral which in turn improves the
results of Kasai's portoenterostomy.
PMID- 24347855
TI - Herlyn-Werner-Wunderlich syndrome presenting with infertility: Role of MRI in
diagnosis.
AB - Herlyn-Werner-Wunderlich syndrome (HWWS), characterized by uterus didelphys,
obstructed hemivagina, and ipsilateral renal agenesis, is an uncommon combined
Mullerian and mesonephric duct anomaly, and its presentation in adulthood is even
rarer. We report here a 22-year-old female presenting with primary infertility
where magnetic resonance imaging (MRI) suggested the diagnosis of HWWS with
endometriosis. In a patient of infertility with endometriosis and unilateral
renal agenesis, diagnosis of HWWS should be suspected and MRI is the
investigation of choice for such anomalies.
PMID- 24347856
TI - MR imaging of carcinoma cervix.
AB - Cervical cancer is a common gynecological malignancy and a frequent cause of
death. Patient outcome depends on tumor stage, size, nodal status, and
histological grade. Correct tumor staging is important to decide the the
treatment strategy. Magnetic Resonance Imaging is accepted as a preferred imaging
modality to assess the prognostic factors.
PMID- 24347857
TI - Transrectal ultrasound-guided aspiration in the management of prostatic abscess:
A single-center experience.
AB - OBJECTIVES: The safety and efficacy of transrectal ultrasound (TRUS) guided
aspiration of prostatic abscess (PA) is known. The objective of this study is to
describe a treatment algorithm for management of PA with TRUS-guided aspiration,
emphasizing on indications and factors predicting the treatment outcome.
MATERIALS AND METHODS: After the institutional review board approval was
obtained, a retrospective study was done of all patients suspected with PA on
digital rectal examination (DRE) and confirmed on TRUS. An 18-gauge two-part
needle was used for aspiration. The real-time TRUS-guided aspiration of PA was
done in the longitudinal axis. The aspiration of pus and the sequential collapse
of cavity was seen "real time." A suprapubic catheter was placed, if the patient
had urinary retention, persistent dysuria, and/or severe lower urinary tract
symptoms (LUTS). Success was defined as complete resolution of the abscess and/or
symptoms. RESULTS: Forty-eight patients were studied with PA, with a mean age of
54.6 +/- 14.6 (range 26-79) years. The DRE diagnosed PA in 22 (45.83%) patients,
while abdominal sonography diagnosed PA in 13 (27.08%) patients. TRUS revealed a
hypoechoic area with internal echoes in all 48 (100%) patients. The diagnosis was
confirmed in all 48 cases with aspiration. The mean size of the lesion was 3.2 +/
1.2 (range 1.5-8) cm. Mean volume aspirated was 10.2 ml (range 2.5-30 ml).
Complete resolution after first aspiration was observed in 20 (41.66%) patients.
An average of 4.1 (range 1-7) aspirations was required for complete resolution
which was seen in 41 patients (85.42%). Seven (14.58%) patients required
transurethral resection (deroofing) of the abscess cavity. We formulated a
treatment algorithm based on the above findings. CONCLUSION: The proposed
algorithm based on our experience suggests that patients with PA larger than 2 cm
with severe LUTS and/or leukocytosis benefit from TRUS-guided aspiration. In
addition, these patients are benefitted from urinary drainage (either perurethral
or suprapubic). The algorithm also suggests that if two attempts of TRUS
aspiration fail, these patients benefit from transurethral drainage.
PMID- 24347858
TI - Rare complications of cesarean scar.
AB - Cesarean scar pregnancy (CSP) and cesarean scar dehiscence (CSD) are the most
dreaded complications of cesarean scar (CS). As the incidence of CS is increasing
worldwide, so is the incidence of CSP, especially in cases with assisted
reproduction techniques. It is of utmost importance to diagnose CSP in the early
first trimester, as it can lead to myometrial rupture with fatal outcome. On the
other hand, CSD may be encountered during pregnancy or in the postpartum period.
CSD in the postpartum period is very rare and can cause secondary postpartum
hemorrhage (PPH) leading to increased maternal morbidity or even death if not
diagnosed and managed promptly. Both complications can be diagnosed on
ultrasonography (USG) and confirmed on magnetic resonance imaging (MRI). These
two conditions carry high morbidity and mortality. In this article, we highlight
the role of imaging in the early diagnosis and management of these conditions.
PMID- 24347859
TI - Increased fetal endocardial echogenicity mimicking endocardial fibroelastosis
following maternal organophosphorus poisoning and its complete regression in
utero.
AB - Fetal endocardial fibroelastosis (EFE) has been diagnosed by antenatal
ultrasonography in the past few years. A typical case of isolated endocardial
fibroelastosis is illustrated here, in a fetus of 22 weeks of gestational age
exposed to maternal organophosphorus poisoning at 20 weeks. No other structural
cardiac or other systemic anomalies were detected in this fetus. The abnormal
fetal echocardiographic features mimicking endocardial fibroelastosis completely
regressed after 14 weeks and a normal full-term baby was delivered. Postnatal
echocardiogram showed normal cardiac parameters. The diagnostic features
mimicking EFE following maternal organophosphorus poisoning at 20 weeks of
gestational age and the subsequent complete reversal of these changes after 14
weeks of diagnosis are reported for the first time in the literature.
PMID- 24347860
TI - Validation of the global reference for fetal weight and birth weight percentiles.
AB - The objective of this study was to evaluate whether the global reference curves
adapted on the basis of WHO data for India and the Hadlock reference curves fit
the population in India and to validate the reference curves. The data were
retrieved retrospectively from the records of women registration for antenatal
care at a charitable maternity hospital in Mumbai, India. All pregnancies were
dated on CRL obtained before 14 weeks. Births before 34(th) week were excluded.
The expected frequencies of birth weights below the 1(st), 5(th), 10(th), 50(th),
90(th), 95(th) and 99(th) centiles from three reference ranges were compared with
observed frequencies. It was found that the WHO generic reference adapted to
India significantly underpredicted the birth weights and that the Hadlock
reference ranges significantly overpredicted the birth weights. The use of
generic reference adapted to Sri Lanka showed a better fit to the observed data.
We concluded that global reference curves adapted on the basis of WHO data for
India and the Hadlock reference ranges do not fit all the population in India and
the charts need validation. Reference charts modified on the basis of data for
Sri Lankan population show a better fit to the observed data, and therefore are
more appropriate for use in clinical practice in South India.
PMID- 24347861
TI - High-resolution ultrasound imaging of cutaneous lesions.
AB - High-resolution variable frequency ultrasound imaging is increasingly being used
in the noninvasive evaluation of various cutaneous diseases. It plays a
complimentary role to physical examination in the assessment of cutaneous
lesions. It is the only imaging modality useful in the evaluation of superficial
cutaneous lesions that are too small to be evaluated on computed tomography (CT)
or magnetic resonance imaging (MRI) and is helpful in reducing invasive
procedures like biopsies and fine needle aspirations. In this article, we seek to
describe the relevance and basic principles of cutaneous ultrasound, imaging
findings of normal skin, current applications of high-resolution ultrasound in
the diagnosis and management of various dermatological conditions, along with the
features of some commonly encountered lesions.
PMID- 24347862
TI - Unilateral sternocostoclavicular hyperostosis in a patient with ankylosing
spondylitis: A case report with color Doppler ultrasonogram findings.
AB - Sternocostoclavicular hyperostosis is a chronic inflammatory disorder affecting
the sternoclavicular joint and upper ribs. There is a strong association with
seronegative spondyloarthropathy in which bilateral involvement is common.
Ultrasonography and Color Doppler findings of this entity have not been described
previously, to the best of our knowledge. We describe the findings in a patient
of ankylosing spondylitis who was referred for unilateral sternoclavicular joint
swelling.
PMID- 24347863
TI - Thermography in ocular inflammation.
AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate ocular
inflammatory and non-inflammatory conditions using commercially available thermal
camera. MATERIALS AND METHODS: A non-contact thermographic camera (FLIR P 620)
was used to take thermal pictures of seven cases of ocular inflammation, two
cases of non-inflammatory ocular pathology, and one healthy subject with mild
refractive error only. Ocular inflammatory cases included five cases of
scleritis, one case of postoperative anterior uveitis, and a case of meibomian
gland dysfunction with keratitis (MGD-keratitis). Non-inflammatory conditions
included a case of conjunctival benign reactive lymphoid hyperplasia (BRLH) and a
case of central serous chorio-retinopathy. Thermal and non-thermal photographs
were taken, and using analyzing software, the ocular surface temperature was
calculated. RESULTS: Patient with fresh episode of scleritis revealed high
temperature. Eyes with MGD-keratitis depicted lower temperature in clinically
more affected eye. Conjunctival BRLH showed a cold lesion on thermography at the
site of involvement, in contrast to cases of scleritis with similar clinical
presentation. CONCLUSION: Ocular thermal imaging is an underutilized diagnostic
tool which can be used to distinguish inflammatory ocular conditions from non
inflammatory conditions. It can also be utilized in the evaluation of tear film
in dry eye syndrome. Its applications should be further explored in uveitis and
other ocular disorders. Dedicated "ocular thermographic" camera is today's need
of the hour.
PMID- 24347864
TI - Research in pediatric surgery: Indian scenario.
PMID- 24347865
TI - Endoscopic treatment of vesico-ureteral reflux: Experience of 99 ureteric
moieties.
AB - AIMS: To study the outcome of endoscopic hyaluronic acid/dextranomer injection in
patients with vesico-ureteric reflux (VUR). MATERIALS AND METHODS: Sixty-three
children were evaluated with a median follow up of 18 months (12-55 months)
before injecting hyaluronic acid/dextranomer in a total of 99 ureteric moieties.
Median age at presentation was 24 months (6-72 months). Primary VUR was the main
presenting diagnosis in 60%. Patients were monitored for urinary tract infection
(UTI), glomerular filtration rate (GFR), renal scarring, persistence, or
appearance of contra-lateral reflux. RESULTS: Grade III VUR was the most common
(38%) followed by Grade IV (24%), Grade V (17%), Grade II (14%), and Grade I
(7%). Most common cause for VUR was Primary (60%), followed by posterior urethral
valve (PUV) (19%), bladder exstrophy (5%), anorectal malformation (ARM),
epispadias, and duplex system. Analysis of patients characteristics at
presentation revealed renal scarring (40%), split renal functions <35% (35%),
recurrent UTI (15%), GFR <50 ml/min/1.73 m(2) (15%), serum creatinine >1.4 mg/dL
(10%). Complete resolution (100%) of Grade I and Grade II VUR was achieved after
single injection. For Grade III VUR, single injection resolved reflux in 85.5%
ureters, 100% resolution was seen after 2(nd) injection. In Grade IV VUR, 1(st)
injection resolved VUR in 83.3% ureters, 95.8% ureters were reflux free after
2(nd) injection, and 100% resolution was seen after 3(rd) injection. In Grade V
VUR, 94% ureters showed absent reflux after three injections. CONCLUSION:
Hyaluronic acid/dextranomer injection holds promise even in higher grades of VUR.
PMID- 24347866
TI - A survey of musculoskeletal and aesthetic abnormalities after thoracotomy in
pediatric patients.
AB - OBJECTIVE: To study the incidence and type of musculoskeletal and aesthetic
abnormalities after thoracotomy in children. MATERIALS AND METHODS: Children
below 12 years of age who had undergone thoracotomy for any condition and have at
least 2 years follow up were included in the study. Detailed assessment of the
patients included: history and general examination, clinical examination of chest
and musculoskeletal system, X-ray chest including bilateral shoulders [antero
posterior (AP), lateral, oblique], X-ray whole spine (AP, lateral, right and left
side bending AP view). RESULTS: Fifty-two pateints were recruited. The incidences
of various clinically and radiologically assessed musculoskeletal and aesthetic
abnormalities observed were: winging of scapula (5.7%), ipsilateral elevation of
shoulder (5.7%), fixation of skin cicatrix to bony thorax (7.7%), maldevelopment
of pectoral muscles (11.5%), asymmetry of the level of nipples (1.9%), rib fusion
(5.7%), crowding of ribs (9.6%), mediastinal shift (3.8%), decreased space
available for lungs (3.8%), Scoliosis with Cobb's angle >10(0) (1.9%).
CONCLUSIONS: The incidences of musculoskeletal and aesthetic abnormalities after
posterolateral thoracotomies in children were low. Longer follow up of patients
after thoracotomy is needed to pick up these abnormalities as the children grow.
PMID- 24347867
TI - Plasma renin activity: An early marker of progressive renal disease in posterior
urethral valves.
AB - INTRODUCTION: A significant number of children with posterior urethral valves
(PUV) develop chronic renal failure (CRF) due to activation of the renin
angiotensin system (RAS). We investigated the role of plasma renin activity (PRA)
in these cases and sought to establish a relationship between the accepted
criteria of renal damage and PRA. AIMS AND OBJECTIVES: The aim of this study is
to establish the relationship between PRA and CRF. MATERIALS AND METHODS: The
records of 250 patients with PUV were reviewed. Multiple linear regression
analysis was used to assess correlations between PRA, grade of reflux, presence
of scars and raised creatinine and decrease in glomerular filtration rates (GFR).
A P < 0.5 was considered as significant. RESULTS: A total of 58 patients were
included. Their mean age was 16 years, range 5.3-24.2 years, mean follow-up
period was 12.6 +/- 3.6 years. At diagnosis, 22/58 (38%) patients were in CRF and
36/58 (62%) patients had normal renal function (RF). The mean PRA after treatment
was higher in those who developed CRF than in those with normal RF (12.6 +/- 10.2
vs. 34.6 +/- 14.2 ng/ml/24 h, P = 0.02). Mean GFR at 1 year of age were 48 +/-
9.8 ml/min/1.73 m(2) and 86 +/- 12.5 ml/min/1.73 m(2) respectively (P = 0.005).
PRA correlated negatively with GFR, t = -2.816. CONFIDENCE INTERVAL: P = 0. 007.
In the temporal plot over a period of 14 years, a rise in PRA preceded the fall
in GFR in patients who developed CRF. CONCLUSIONS: This study shows that RAS is
activated earlier in kidneys susceptible to damage. PRA could be investigated as
a marker for the early detection and prevention of ongoing renal damage.
PMID- 24347868
TI - Congenital double duodenal diaphragms in an infant.
AB - Duodenal stenosis usually occurs in isolation and has a variable presentation in
infancy due to partial obstruction. An unusual case of congenital double duodenal
diaphragms in an infant presenting as failure to thrive has been described and
pertinent literature has been reviewed herein. Excision of webs with double
Heineke-Mikulicz closure was performed.
PMID- 24347869
TI - Neonatal segmental enteritis due to cow's milk allergy.
AB - Cow's milk protein allergy (CMPA) typically presents with persistent diarrhea or
dysentery, vomiting and bleeding per rectum in young infants. CMPA is reported to
mimic Hirschsprung's disease and malrotation. We report, a neonate who presented
with recurrent attacks of segmental enteritis due to CMPA and the last episode
presented with signs of peritonitis. He improved dramatically after elimination
of cow's milk from his diet. CMPA should be considered in artificially fed babies
with surgical abdomen and atypical clinical signs and symptoms.
PMID- 24347870
TI - Single piece artificial urinary sphincter for secondary incontinence following
successful repair of post traumatic urethral injury.
AB - Post traumatic urethral injury is uncommon in children. The management of this
condition is dependent on the severity of injury. Initial suprapubic cystostomy
with delayed repair is the conventional treatment. Successful reconstruction of
urethral injury may be followed by urethral stricture, incontinence, impotence,
and retrograde ejaculation. Successful repair of post traumatic urethral injury
followed by secondary incontinence in children has not been well addressed in
literature. We report the management of one such child, with satisfactory outcome
with implantation of a new model of single piece artificial urinary sphincter in
the bulbar urethra by perineal approach.
PMID- 24347871
TI - Malrotation with midgut volvulus associated with perforated ileal duplication.
AB - Duplication of the alimentary tract is an important surgical condition. It may
occur anywhere in the gastrointestinal tract. An important complication of this
entity is perforation of the normal or abnormal gut. Malrotation with midgut
volvulus can be a surgical emergency. We present a patient, who presented as
malrotation with midgut volvulus associated with perforated ileal duplication.
The patient was successfully managed.
PMID- 24347872
TI - Hydatid cyst within a choledochal cyst.
AB - A 5 year 4 months old male child presenting with pain abdomen and jaundice was
diagnosed to have type 1 choledochal cyst on ultrasonography and magnetic
resonance cholangio pancreatography. On exploration, the cystic dilatation of
common bile duct was found to have a hydatid cyst (HC) inside it. The per
operative findings were confirmed by histopathology. Association of HC within a
choledochal cyst is extremely rare and has been reported only twice before in the
available English literature.
PMID- 24347873
TI - Multiple magnet ingestion: An uncommon cause of peritonitis.
AB - Foreign body ingestion is common in infants and young children and they pass
spontaneously in most of the cases. Magnetic foreign bodies, though not very
common, require early intervention to avoid severe gastrointestinal
complications. We report a case of multiple magnet ingestion who presented with
peritonitis.
PMID- 24347874
TI - Mediastinal hemangioma: Masquerading as pleural effusion.
AB - We present a rare case of mediastinal hemangioma in a 4-year-old child. The child
presented with cough and fever and the chest radiograph revealed right pleural
effusion. On further work-up with chest computed tomography mediastinal cystic
mass occupying the right hemithorax was identified. The cystic mass was resected
completely through a right thoracotomy. Histopathological examination established
the final diagnosis of mediastinal capillary hemangioma.
PMID- 24347875
TI - Report of a malignant melanoma arising in a small congenital nevus in a 3-year
old child.
PMID- 24347876
TI - Bowel perforation due to retained enema nozzle in a patient of anorectal
malformation.
PMID- 24347877
TI - Research to knowledge.
PMID- 24347878
TI - Clinical and radiographic evaluation of single-visit and multi-visit endodontic
treatment of teeth with periapical pathology: An in vivo study.
AB - OBJECTIVES: To compare and evaluate the clinical symptoms and radiographic
evidence of periapical healing after endodontic treatment of teeth with
periapical pathology when completed in one-visit or two-visits with ApexCal paste
at 3, 6, and 12 months. MATERIALS AND METHODS: A total of 57 patients requiring
root canal treatment on 64 single rooted teeth with periapical pathology
preoperatively were included. The teeth were assigned randomly into two groups
and treated according to standardized protocol. The teeth in group I (n = 34)
were obturated at the first visit, while those in group II (n = 30) were
medicated with ApexCal paste, and obturated in a second visit 7 days later.
Patients were recalled at intervals of 3, 6, and 12 months to evaluate the
treated teeth both clinically and radiographically for periapical healing.
RESULTS: Mann - Whitney U test showed no difference between groups I and II.
Wilcoxon signed rank test showed significant decrease in mean periapical index
(PAI) scores within both groups during 12 months evaluation. The level of
significance used was P < 0.05. CONCLUSIONS: Both groups exhibited equally
favorable healing at 12 months, with no statistically significant differences
between groups I and II.
PMID- 24347879
TI - Sealing ability of three single-cone obturation systems: An in-vitro glucose
leakage study.
AB - AIM: The aim of this study is to compare the corono-apical sealing ability of
three single-cone obturation systems using a glucose leakage model. MATERIALS AND
METHODS: A total of 90 extracted maxillary single rooted teeth were selected and
their crowns were cut. The root canal of each sample was instrumented using a
rotary crown down technique and then divided into four experimental (n = 20 each)
and two control groups (n = 5 each). Samples in the experimental groups were
filled as follows: Group 1, cold lateral condensation using Gutta-percha/AH Plus;
Group 2, single-cone Gutta-percha and AH Plus; Group 3, single-cone Gutta
percha/and GuttaFlow2; Group 4, single-cone Resilon/RealSeal SE after 7 days, the
sealing ability of root canal fillings was tested at different time intervals
using glucose leakage model. Glucose leakage values were measured using a
spectrophotometer and statistically analyzed. RESULTS: The four experimental
groups presented significantly different glucose leakage values at all test
periods (P < 0.05). At the end of the observation period, the cumulative glucose
leakage values of Groups 3 and 4 were significantly lower than those of Groups 1
and 2 (P < 0.05). CONCLUSION: Gutta-percha/GuttaFlow2 or Resilon/RealSeal SE
combinations provided the superior sealing ability over the lateral condensation
technique.
PMID- 24347880
TI - Evaluation of mineral trioxide aggregate as root canal sealer: A clinical study.
AB - AIM: The aim of this study was to compare the clinical and radiological outcome
of mineral trioxide aggregate (MTA) or epoxy resin as a root canal sealer
compared with zinc oxide eugenol sealer. MATERIALS AND METHODS: 45 single rooted
teeth with periapical index Score 2 or more were allotted to three groups with 15
teeth in each group. Root canal treatment was performed in two visits and
obturated with Gutta-percha as obturating material and zinc oxide eugenol as
sealer in Group 1, epoxy resin as sealer in Group 2 and MTA mixed with propylene
glycol as sealer in Group 3. Visual analog scale, periapical index and VixWin
digital Pro image analysis software were used for evaluation. The quantitative
data was analyzed by t-test and analysis of variance. Ordinal data was analyzed
by Wilcoxon's signed rank test, Mann-Whitney and Kruskall-Wallis test. RESULTS:
Results suggested that there exists no statistically significant difference in
clinical or radiological outcome of root canal therapy with three different types
of sealers used in this study. CONCLUSIONS: MTA could be used as a root canal
sealer with equal effectiveness compared with epoxy resin and zinc oxide eugenol
sealers. Further long-term studies should be carried out to prove the
effectiveness.
PMID- 24347881
TI - The effect of various primers on shear bond strength of zirconia ceramic and
resin composite.
AB - AIMS: To determine the in vitro shear bond strengths (SBS) of zirconia ceramic to
resin composite after various primer treatments. MATERIALS AND METHODS: Forty
zirconia ceramic (Zeno, Wieland Dental) specimens (10 mm in diameter and 2 mm
thick) were prepared, sandblasted with 50 MUm alumina, and divided into four
groups (n = 10). Three experimental groups were surface treated with three
primers; CP (RelyX Ceramic Primer, 3M ESPE), AP (Alloy Primer, Kuraray Medical),
and MP (Monobond Plus, Ivoclar Vivadent AG). One group was not treated and served
as the control. All specimens were bonded to a resin composite (Filtek Supreme
XT, 3M ESPE) cylinder with an adhesive system (Adper Scotchbond Multi-Purpose
Plus Adhesive, 3M ESPE) and then stored in 100% humidity at 37 degrees C for 24 h
before SBS testing in a universal testing machine. Mean SBS (MPa) were analyzed
with one-way analysis of variance (ANOVA) and the Tukey's Honestly Significant
Difference (HSD) test (alpha = 0.05). RESULTS: Group AP yielded the highest mean
and standard deviation (SD) value of SBS (16.8 +/- 2.5 MPa) and Group C presented
the lowest mean and SD value (15.4 +/- 1.6 MPa). The SBS did not differ
significantly among the groups (P = 0.079). CONCLUSIONS: Within the limitations
of this study, the SBS values between zirconia ceramic to resin composite using
various primers and untreated surface were not significantly different.
PMID- 24347882
TI - Marginal sealing ability of silorane and methacrylate resin composites in class
II cavities: A scanning electron microscopic study.
AB - AIM AND OBJECTIVES: To comparatively evaluate the microleakage and microgap
formation along the gingival margin in class II cavities restored with silorane
resin composite and methacrylate resin composite with and without flowable resin
liner. MATERIALS AND METHODS: Sixty human mandibular premolars were distributed
into three groups, each group containing 20 teeth (n = 20). Mesial (subgroup A)
and distal (subgroup B) box cavities were prepared with gingival margin above and
below cemento enamel junction (CEJ), respectively, in each tooth and restored as
follows - Group I - Silorane resin composite with self-etch primer and bond
(Filtek P90, 3M ESPE MN, USA). Group II - Methacrylate resin composite (Filtek
P60, 3M ESPE MN, USA) and self-etch adhesive (Adper Easy one, 3M ESPE MN, USA).
Group III - Methacrylate resin composite with self-etch adhesive and a flowable
resin liner (Filtek Z350 XT, 3M ESPE MN, USA). The teeth were thermocycled and
immersed in 50% silver nitrate solution before sectioning. The specimens were
observed under scanning electron microscope for dye penetration and microgap
formation. The data was subjected to statistical analysis using Kruskal-Wallis
test and Mann-Whitney U test using SPSS version 18. RESULTS: Subgroup A in all
the three groups showed significantly less microleakage and microgap formation
compared to subgroup B with P < 0.05. Intergroup comparison of subgroup A did not
show statistically significant difference, whereas subgroup B showed
statistically significant difference for microleakage between group I and group
II (P = 0.003), group III and group II (P = 0.002). CONCLUSION: Silorane resin
composite and methacrylate resin with liner showed significantly less
microleakage in class II cavities along the gingival margin placed below CEJ
compared to methacrylate resin without liner. All the study groups showed less
microleakage and microgap formation along the gingival margin placed above CEJ.
PMID- 24347883
TI - Comparative evaluation of the efficacy of three different irrigation devices in
removal of debris from root canal at two different levels: An in vitro study.
AB - AIM: The purpose of this in vitro study was to evaluate the cleaning efficacy of
NaviTip, Max-i-Probe and Endovac in removal of debris from the root canal at 1.5
and 3.5 mm from the apex. MATERIALS AND METHODS: Forty single-rooted teeth were
divided into four groups according to the root canal irrigation system (EndoVac,
NaviTip, Max-i-Probe, and control). Instrumentation was done using ProFile 0.06
taper series to MAF #40. Root canals were irrigated after each file size with 1
ml of 5% NaOCl. For final irrigation 5 ml of 5% NaOCl and 17%
ethylenediaminetetraacetic acid (EDTA) was used. Each group was irrigated with a
different irrigation device. Four micron thick serial sections were prepared at
1.5 and 3.5 mm from the apical level and photographs were taken for the analysis.
The influence of the irrigation system was evaluated using a one-way analysis of
variance (ANOVA) test and unpaired t-test (P < 0.05). RESULTS: Endovac showed
significantly least amount of mean percentage debris followed by Max-i-probe and
NaviTip at both levels (P < 0.05). In all the experimental groups, significantly
less amount of mean percentage debris was seen at 3.5 mm level than at 1.5 mm
level (P < 0.05). However, the difference was statistically insignificant in case
of Endovac irrigation system group. CONCLUSIONS: Amongst all the experimental
groups, Endovac removed significantly more debris followed by Max-i-probe and
NaviTip at both levels.
PMID- 24347884
TI - Evaluation of immediate and delayed post space preparation on sealing ability of
Resilon-Epiphany and Gutta percha-AH plus sealer.
AB - AIM: To evaluate the influence of immediate and delayed post space preparation on
sealing ability of Resilon-Epiphany and Gutta percha-AH plus. MATERIALS AND
METHODS: Eighty extracted permanent maxillary central and lateral incisors were
decoronated. Roots canals were prepared and obturated. Samples were divided into
four groups depending on the time of post space preparation and obturated
material. Group I and II: Immediate and delayed post space preparation
respectively with Gutta percha/AH plus as obturating material. Group III and IV:
Immediate and delayed post space preparation with Resilon/Epiphany as the
obturating material. The samples were kept in methylene blue dye, sectioned and
then measured under stereomicroscope and studied under SEM. STATISTICAL ANALYSIS:
The data was subjected to statistical analysis using unpaired t-test. RESULTS:
There was significant difference found between immediate and delayed post space
preparation in Resilon-Epiphany group (P = 0.0109) as well as in AH plus-GP group
(<0.0001). Difference in the sealing ability of the two materials was seen in
delayed group (P = 0.0202). No statistically significant result was found between
the two obturating materials when post space was prepared immediately (P =
0.0875). CONCLUSION: Within the limitations of this study, there was
significantly less leakage when post space is prepared immediately in both the
groups. Resilon-Epiphany shows better results when post space is delayed amongst
the two whereas in immediate post space preparation there is no significant
difference.
PMID- 24347885
TI - Configuration of the inferior alveolar canal as detected by cone beam computed
tomography.
AB - AIMS: The aim of this study is to evaluate the course of the inferior alveolar
canal (IAC) including its frequently seen variations in relation to root apices
and the cortices of the mandible at fixed pre-determined anatomic reference
points using cone beam volumetric computed tomography (CBVCT). MATERIAL AND
METHODS: This retrospective study utilized CBVCT images from 44 patients to
obtain quantifiable data to localize the IAC. Measurements to the IAC were made
from the buccal and lingual cortical plates (BCP/LCP), inferior border of the
mandible and the root apices of the mandibular posterior teeth and canine.
Descriptive analysis was used to map out the course of the IAC. RESULTS: IACs
were noted to course superiorly toward the root apices from the second molar to
the first premolar and closer to the buccal cortical plate anteriorly. The canal
was closest to the LCP at the level of the second molar. In 32.95% of the cases,
the canal was seen at the level of the canine. CONCLUSIONS: This study indicates
that caution needs to be exercised during endodontic surgical procedures in the
mandible even at the level of the canine. CBVCT seems to provide an optimal, low
dose, 3D imaging modality to help address the complexities in canal
configuration.
PMID- 24347886
TI - Dentinal defects before and after rotary root canal instrumentation with three
different obturation techniques and two obturating materials.
AB - AIM: To evaluate the role of rotary root canal instrumentation followed by
obturation with three different techniques and two different materials on the
incidence of dentinal defects. MATERIALS AND METHODS: One hundred and sixty
mandibular premolars were divided into eight groups (n = 20). Group I was left
untreated and served as control. The other seven groups were prepared with
profile rotary instruments till #40.06 taper. After preparation, group II was
left unfilled, groups III, IV, and V were obturated with Gutta-percha and AH Plus
sealer using passive technique, lateral compaction and warm vertical compaction,
respectively. Groups VI, VII, and VIII were obturated with Resilon and Realseal
sealer using passive technique, lateral compaction, and warm vertical compaction,
respectively. Roots were then sectioned at 3, 6, and 9 mm from the apex and
inspected under a stereomicroscope (50*) for dentinal defects. Chi-square test
was performed to compare the incidence of dentinal defects between the groups (P
< 0.05). RESULTS: The unprepared control group had no dentinal defects. The
instrumentation group (group II) and the obturation group (groups III-VIII)
showed significantly more defects than the uninstrumented control group (group I)
(P < 0.001). There was no significant difference between the root canal
obturating techniques (group III-VIII) when compared with the instrumentation
group (group II). On inter group comparison among the obturation groups the
number of defects after lateral compaction with Gutta-percha (group IV) was
significantly larger than passive Gutta-percha obturation (group III) (P < 0.05).
CONCLUSIONS: The results suggest that root canal instrumentation significantly
influenced the incidence of dentinal defects or fracture. Dentinal defects were
more significantly attributed to the role of root canal instrumentation rather
than the type of obturation technique or material. Lateral compaction with Gutta
percha significantly produces more defects than passive Gutta-percha obturation.
PMID- 24347887
TI - Effect of dietary solvents on the strength of nanocomposite, compomer, glass
ionomer cement: An in-vitro study.
AB - BACKGROUND: Intraoral degradation of resin restorative materials involves both
mechanical and chemical factors. Thus, an in vitro study was conducted to compare
the strength of nanocomposite to commonly used esthetic restorative materials in
simulated in vivo conditions. AIM: The aim of this study was to determine the
influence of dietary solvents on the strength of nanocomposite and other esthetic
restorative materials. MATERIALS AND METHODS: Three test groups (nanocomposite,
compomer and glass ionomer cement) each containing 60 pre-conditioned samples,
divided into four subgroups of 15 samples each and conditioned in different
dietary solvents, were subjected to shear punch test in custom designed shear
punch apparatus in Instron Universal Testing Machine. STATISTICAL ANALYSIS:
Descriptive statistics, one way analysis of variance (ANOVA), paired t-test were
implied. RESULTS: One-way ANOVA revealed nanocomposite to bear most shear punch
strength post-conditioning, as compared with the other two test materials.
CONCLUSION: Nanocomposite yielded better strength than the other two test
materials, indicating its universal application as a restorative material.
PMID- 24347888
TI - Comparison of antimicrobial efficacy of propolis, Morinda citrifolia, Azadirachta
indica (Neem) and 5% sodium hypochlorite on Candida albicans biofilm formed on
tooth substrate: An in-vitro study.
AB - INTRODUCTION: Endodontic infections are polymicrobial in nature. Candida albicans
is the most common fungus isolated from failed endodontic cases. The constant
increase in antibiotic resistant strains and side-effects caused by synthetic
drugs has prompted researchers to look for herbal alternatives such as propolis,
Morinda citrifolia and Azadirachta indica (Neem) etc., since, the gold standard
for irrigation, i.e., sodium hypochlorite has many disadvantages. MATERIALS AND
METHODS: Extracted human mandibular premolars were biomechanically prepared,
vertically sectioned, placed in tissue culture wells exposing the root canal
surface to C. albicans grown on Sabouraud Dextrose Agar to form a biofilm. At the
end of 2 days, all groups were treated with test solutions and control for 10 min
and evaluated for Candida growth and number of colony forming units. The readings
were subjected to statistical analysis using analysis of variance and post hoc
Tukey tests. RESULTS: Sodium hypochlorite and propolis groups exhibited highest
antimicrobial efficacy against C. albicans with no statistically significant
difference. It was followed by the A. indica (Neem) group. M. citrifolia had
limited antifungal action followed by the negative control group of saline.
CONCLUSION: According to the results of this study, propolis can be used as an
effective antifungal agent similar to that of sodium hypochlorite, although long
term in vivo studies are warranted.
PMID- 24347889
TI - Influence of preheating the bonding agent of a conventional three-step adhesive
system and the light activated resin cement on dentin bond strength.
AB - AIMS: to evaluate the influence of preheating the bonding agent (Scotchbond
Multipurpose Adhesive/3M ESPE) and the light-activated resin cement (RelyX
Venner/3M ESPE) on dentin microtensile bond strength. MATERIALS AND METHODS: The
exposed flat dentin surface of 40 human third molars were randomly distributed
into four groups for cementation (SR Adoro/Ivoclar Vivadent) (n = 10): G1-bond
and resin cement, both at room temperature (22 degrees C), G2-bond preheated to
58 degrees C and cement at room temperature (22 degrees C), G3-bond at room
temperature (22 degrees C) and the cement preheated to 58 degrees C, G4-bond
preheated to 58 degrees C and cement preheated to 58 degrees C. Sticks of
dentin/block set measuring approximately 1 mm(2) were obtained and used for the
microtensile bond strength test. All sticks had their failure mode classified.
STATISTICAL ANALYSIS USED: Factorial analysis of variance was applied, 2 * 2
(bond * cement) (P < 0.05). RESULTS: Preheating the bonding agent (P = 0.8411) or
the cement (P = 0.7155), yielded no significant difference. The interaction bond
* cement was not significant (P = 0.9389). CONCLUSIONS: Preheating the bond
and/or the light-activated resin cement did not influence dentin bond strength or
fracture failure mode.
PMID- 24347890
TI - Comparative evaluation of intracanal sealing ability of mineral trioxide
aggregate and glass ionomer cement: An in vitro study.
AB - AIMS: The purpose of this study was to compare the sealing ability of Mineral
Trioxide Aggregate (MTA) and Glass Ionomer Cement (GIC) when used over gutta
percha as intracanal sealing materials. The study also evaluated the sealing
ability of Zinc oxide eugenol (ZOE) cement and Acroseal sealer. MATERIALS AND
METHODS: Teeth were obturated with gutta-percha using sealer ZOE (group A, C, D)
and Acroseal (group B). The groups were further divided into 2 subgroups (15
premolars each) on the basis of intracanal sealing material used: GIC subgroups
(A1, B1) and MTA in subgroups (A2, B2). The clearing technique was used in this
study for leakage evaluation. Seventy mandibular premolars were prepared using
step-back technique and divided into experimental groups A and B (30 premolars
each) and the positive and negative control groups C and D (5 premolars each).
STATISTICAL ANALYSIS USED: Coronal microleakage was determined under
stereomicroscope using 15X magnification. Data was statistically analyzed using
one-way ANOVA followed by Post-Hoc Multiple comparison (Bonferroni). RESULTS: MTA
group leaked significantly less than GIC group (P < 0.05). Acroseal exhibited
better sealing ability than ZOE sealer. Teeth with no intracanal barrier showed
almost complete leakage. CONCLUSIONS: MTA may be preferred over GIC as an
intracanal barrier.
PMID- 24347891
TI - An in-vivo comparative evaluation of two herbal extracts Emblica officinalis and
Terminalia Chebula with chlorhexidine as an anticaries agent: A preliminary
study.
AB - AIM: To compare the effect of 20% aqueous extract of Terminalia chebula and
Emblica officinallis with chlorhexidine as an anticaries mouthwash - an in vivo
study. METHODOLOGY: 20% aqueous extract of Terminalia chebula and Emblica
officinalis were prepared. Forty five high caries risk patients were divided into
group 1,2,3 [ n=15]and asked to rinse with 20% aqueous extract of Terminalia
chebula and Emblica officinalis, 0.2% Chlorhexidine for 40 seconds respectively.
Salivary samples were collected for pH, buffering capacity before and after
rinsing at repeated intervals of 10, 30,60 and 90 minutes and except for
microbial analysis for which it was collected before and 90 minutes after
rinsing. The pH and the buffering capacity analysis was done using chairside kit
and percentage of reduction of Streptococcus mutans and Lactobacillus were
tabulated and statistically analyzed. RESULTS: For salivary pH, Group 2 showed
the highest peak value followed by group 1. For salivary buffering capacity,
there was no significant difference between any of the groups. For microbial
count, highest percentage of reduction was seen in group 2 followed by group 1
and 3. However group 3 was more efficient at 90 minutes followed by group 1 and
group 2. CONCLUSION: The aqueous extract of Embilica officinalis extract and
Terminalia chebula was more effective anticaries mouthwash but with less time of
action than chlorhexidine.
PMID- 24347892
TI - Evaluation of micro-shear bond strength of resin modified glass-ionomer to
composite resins using various bonding systems.
AB - AIM: The aim was to compare the micro-shear bond strength between composite and
resin-modified glass-ionomer (RMGI) by different adhesive systems. MATERIALS AND
METHODS: A total of 16 discs of RMGI with a diameter of 15 mm and a thickness of
2 mm were randomly divided into four groups (n = 4). Four cylinders of composite
resin (z250) were bonded to the RMGI discs with Single Bond, Clearfil SE Bond and
Clearfil S3 Bond in Groups 1-3, respectively. The fourth group was the control.
Samples were tested by a mechanical testing machine with a strain rate of 0.5
mm/min. Failure mode was assessed under a stereo-microscope. RESULTS: The means
of micro-shear bond strength values for Groups 1-4 were 14.45, 23.49, 16.23 and
5.46 MPa, respectively. Using a bonding agent significantly increased micro-shear
bond strength (P = 0.0001). CONCLUSION: Micro-shear bond strength of RMGI to
composite increased significantly with the use of adhesive resin. The bond
strength of RMGI to composite resin could vary depending upon the type of
adhesive system used.
PMID- 24347893
TI - An in vitro comparison of root canal length determination by DentaPort ZX and
iPex apex locators.
AB - AIM: THE AIM OF THE PRESENT STUDY IS TO EVALUATE AND TO COMPARE THE ACCURACY OF
TWO ELECTRONIC APEX LOCATORS (EALS): DentaPort ZX and iPex, at a position 0.5 mm
short of the apical foramen. MATERIALS AND METHODS: Thirty single-rooted,
mandibular premolar teeth were selected. Standard access cavities were prepared
and the actual length (AL) was calculated. The samples were then embedded in
alginate and the electronic measurements were determined and recorded. RESULTS:
The results obtained showed that in determining the root canal length with a
tolerance level of +/-0.5 mm, i.e., AL +/- 0.5 mm, DentaPort ZX was accurate in
93.3% of the samples and iPex was accurate in 90% of the samples at a position
0.5 mm short of the apical foramen. CONCLUSION: A strong correlation was seen
between the two electronic methods and AL and also in between the two EALs,
showing the possibility of their use to measure the root canal length. No
statistically significant difference was found between both the apex locators.
PMID- 24347894
TI - Surface geometry of various nanofiller composites using different polishing
systems: A comparative study.
AB - AIM: This in vitro study assessed the surface quality of three nanoparticle
composites with four commercially available polishing systems. MATERIALS AND
METHODS: A total of 180 specimens (10 * 2 mm) were prepared in metal molds using
three nanocomposites, Filtek Z-350 XT, Ceram-X Mono, and Tetric N-Ceram. Sixty
specimens of each material were then randomly assigned to five study groups.
Control specimens were left untreated and the remaining specimens were subjected
to polishing with SpinBrite, CompoMaster, AstroPol, and SofLex polishing systems.
Average roughness (Ra) and average ten-point roughness (Rz) were calculated using
Perthometer, and the data were analyzed by two-way analysis of variance (ANOVA)
and post-hoc Tukey's tests. RESULTS: For all the materials, the roughest surfaces
were observed for control specimens, with no statistically significant
differences between the material groups. For Filtek Z-350 XT, the decrease in
surface roughness after two-step polishing was insignificant. For Ceram-X,
SpinBrite specimens showed similar degree of roughness as control specimens. For
Tetric N-Ceram, no significant decrease in roughness was observed after one-step
polishing. Two-way ANOVA (interaction of subgroups and groups) did not show a
significant association with the outcome. CONCLUSIONS: For nanofilled composites
(Filtek Z-350 XT), the surface roughness decreased with the increase in number of
polishing steps, whereas one-step and multi-step polishing procedures produced
similar quality of smoothness for nanohybrid composites (Ceram-X, Tetric N
Ceram). Ra and Rz values of surface roughness are a function of type of
finishing/polishing only.
PMID- 24347895
TI - In vitro evaluation of the effect of two finishing and polishing systems on four
esthetic restorative materials.
AB - AIM: To determine the surface roughness of esthetic restorative materials after
finishing and polishing. MATERIALS AND METHODS: All 60 specimens were divided
into four groups. Group I: Nanocomposite, Z 350 XT (3M ESPE, USA); Group II:
Microhybrid composite, Z 250 (3M ESPE, USA); Group III: Compomer, Dyract XP (LD
Caulk/Dentsply, USA); and Group IV: Resin modified glass ionomer cement (GIC),
Fuji II LC (GC, Japan). Each group was again divided into three subgroups.
Subgroup A: Sof-Lex (3M ESPE); Subgroup B: Super-Snap Rainbow finishing and
polishing kit (Shofu INC, Japan); and Subgroup C: Control Mylar strip. Surface
roughness was determined by Perthen Perthometer S6P profilometer. RESULT: Filtek
Z350 XT showed minimum surface roughness followed by Filtek Z250, Dyract XT and
Fuji II LC. Super-Snap exhibited less surface roughness than Sof-Lex polishing
systems. STATISTICAL ANALYSIS: One-way analysis of variance (ANOVA) followed by
multiple post hoc comparisons using least square difference method and unpaired t
test was used. CONCLUSION: Filtek Z350 XT with Mylar strip exhibited least
surface roughness.
PMID- 24347896
TI - Comparative outcome of revascularization in bilateral, non-vital, immature
maxillary anterior teeth supplemented with or without platelet rich plasma: A
case series.
AB - Loss of pulp vitality in an immature permanent tooth arrests root development.
This leads to tooth with open apex and weak lateral dentinal walls. Management of
such necrotic teeth with immature roots poses several treatment challenges. The
documented study was performed to evaluate and compare apexogenesis induced by
revascularization, with and without platelet rich plasma (PRP) in non-vital,
immature anterior teeth. Three patients having bilateral, non-vital, immature
maxillary central incisors with apical periodontitis were recruited after
institutional ethical clearance. Subsequent to chemo-mechanical preparation,
revascularization with and without PRP was randomly induced in either of the
tooth. The cases were followed-up clinically and radiographically at 6 and 12
months. There was a marked difference in periapical healing, apical closure and
dentinal wall thickening of teeth treated by revascularization with PRP.
PMID- 24347897
TI - Management of a large periapical lesion using Biodentine(TM) as retrograde
restoration with eighteen months evident follow up.
AB - Injury to anterior teeth is a common event. It requires a treatment approach that
assures the complete biologic healing and functional restoration of the tooth or
teeth involved. A cystic lesion, which is unable to heal nonsurgically, heals
well with surgical intervention and use of mineral trioxide aggregate (MTA) as
retrograde filling has been reported in literature. Another material with largely
improved handling properties; Biodentine(TM) (Septodont, St. Maurdes Fosses,
France) was introduced in 2011. It is a calcium silicate based material and
manufacturers claim that it can be used for crown and root dentin repair
treatment, repair of perforations or resorptions, apexification, and root end
fillings. This article presents a case report of surgical management of a large
cystic lesion using Biodentine(TM) as retrograde filling material which has not
been reported in literature so far. Eighteen months radiographic follow-up
exhibited completely healed cystic lesion.
PMID- 24347898
TI - Endodontic management of a four rooted retained primary maxillary second molar.
AB - The presence of accessory roots is rare in the primary dentition. Complete
knowledge and understanding of tooth anatomy is essential to carry out high
quality dental treatment with excellent outcome. In addition, the persistent
primary tooth and its missing permanent successor in the dental arch pose several
hurdles in front of the clinician due to doubtful survival of primary tooth. In
this paper, highlights the root canal treatment of a rarest four rooted retained
primary maxillary second molar.
PMID- 24347899
TI - Role of mineral trioxide aggregate in management of external root resorption.
AB - External root resorption (ERR) is a lytic process occurring in the cementum or
cementum and dentin of the roots of teeth. Here we report a case of inflammatory
ERR in a mandibular right molar in a 22-year-old male patient with history of
incomplete root canal treatment with the same. Considering the biological
properties of mineral trioxide aggregate cement, especially its alkalinity and
sustained calcium hydroxide release, this material was used for the treatment of
ERR, followed by permanent prosthesis. The clinical and radiographic follow-up
for 24 months revealed that treated teeth were functional, the progression of the
ERR had ceased, the resorptive area were replaced with newly formed bone and
periapical radiolucencies was healed.
PMID- 24347900
TI - An unusual occurrence of bilaterally geminated mandibular second premolars
resulting in premolar molarization: A case report.
AB - Gemination refers to an attempt by a single tooth bud to divide, with a resultant
formation of either a large tooth with a bifid crown or two completely divided
teeth throughout the crown and root. This report describes a rare case of
bilateral gemination of permanent mandibular second premolar tooth giving rise to
molarization of premolars. The mesiodistal width of these teeth is similar to
mandibular molars, but the cervicoocclusal width is lesser than that of the molar
tooth. This paper also discusses the potential orthodontic, periodontal, and
endodontic complications of premolar molarization.
PMID- 24347901
TI - Who is Responsible for this Entire Hustle Bustle: Let's Put on the 'Blue Hat'.
PMID- 24347902
TI - Significance of the development of a cardiovascular disease surveillance and
reporting system in India.
AB - Cardiovascular disease (CVD) is the single largest cause of global morbidity and
mortality and is the leading cause of death in the Indian subcontinent projected
to contribute to deaths expected to double by 2015. The social and economic
impact of these staggering projections highlight the need for a centralized
effort to monitor and evaluate behavioral and physiological risk factors for CVD.
Limited evidence on existing surveillance systems suggest that the key to an
effective monitoring and evaluation (M and E) program for CVD surveillance in
India relies upon the World Health Organization's STEP-wise model. Key
recommendations for the Ministry of Health include the development of a national
CVD surveillance program with expertise and a quality-improvement mechanism to
receive continuous input from similar surveillance programs in likeminded
countries. Structure of the surveillance system would include; (1) the
development of process measures for CVD risk factor' based surveillance M and E
systems for early detection of CVD at the local-level, (2) the development of
trigger based data reporting responsibilities to State-based monitoring teams
including incentives for accuracy in data reporting and the use of data-driven
evidence to target risk specific intervention and prevention on Central
Government monitoring teams with reporting feedback to the State and local-levels
and (3) the creation of health policy to require the use of data to target risk
specific prevention for intervention and developing local technical capacity.
Such a system would provide significant cost and social benefits, presenting an
evidence based data driven cost-effective business case for scale-up and
potential use in areas comprising similar demographics. Future research should
focus on the inclusion of a systematic critique of the reported data for the
challenges to surveillance systems in India and the examination of the effect of
an incentivized reporting system on the states. Further inquiry into the types of
reporting and lessons from other countries' surveillance programs with
alternative strategies to a national approach should address potential imitations
at the ground or peripheral levels.
PMID- 24347903
TI - Palliative radiotherapy in locally advanced head and neck cancer after failure of
induction chemotherapy: comparison of two fractionation schemes.
AB - CONTEXT: Among patients with locally advanced head and neck squamous cell cancers
(LAHNSCC), the prognosis after nonresponse or progression despite induction
chemotherapy (IC) is dismal, and further treatment is often palliative in intent.
Given that nonresponse to chemotherapy could indicate subsequent radioresistance,
we intended to assess the outcomes with two different fractionation schemes.
AIMS: To compare the outcomes of two fractionation schemes- 'standard'
(consisting 3GyX5 daily fractions for 2 consecutive weeks) versus 'hybrid' (6GyX3
fractions on alternate days during the 1(st) week, followed by 2GyX5 daily
fractions in the 2(nd) week). SETTINGS AND DESIGN: Prospective randomized
controlled two-arm unblinded trial. MATERIALS AND METHODS: Patients with locally
advanced oropharyngeal, laryngeal, and hypopharyngeal cancers treated with a
minimum of two cycles of taxane, platinum, and fluorouracil-based IC were
eligible if residual disease volume amounted <30 cm(3). Kaplan-Meier survival
curves were compared by the log-rank test. Response rates were compared using the
unpaired t-test. Quality of life (QOL) was measured via patient reported
questionnaires. RESULTS: Of the initially enrolled 51 patients, 45 patients (24
from standard arm, and 21 from the hybrid arm) were eligible for analysis.
Despite being underpowered to attain statistical significance, there still seemed
to be a trend towards improvement in progression-free (Hazard ratio (HR) for
progression: 0.5966; 95% CI 0.3216-1.1066) and overall survival (HR for death:
0.6062; 95% CI 0.2676-1.3734) with the hybrid arm when compared to the standard
arm. Benefits were also observed with regards to response rates and QOL. Rate of
complications were similar in both arms. CONCLUSIONS: In comparison to the
routinely used palliative fractionation scheme of 30 Gray (Gy) in 10 fractions
(Fr), the use of hybrid fractionation which integrates hypofractionation in the
1(st) week, followed by conventional fractionation in the 2(nd) week, could
possibly offer better response rates, QOL increments, and potential survival
benefits among LAHNSCC patients even after failing to respond to IC.
PMID- 24347904
TI - Psychiatric morbidity, pain perception, and functional status of chronic pain
patients in palliative care.
AB - CONTEXT: Psychological factors, such as that exist when we experience pain, can
profoundly alter the strength of pain perception. AIM: The study aims to estimate
the prevalence of psychiatric disorders, and its association with perception of
pain and functional status in chronic patients in palliative care. MATERIALS AND
METHODS: The sample was selected via simple randomisation and post consent were
assessed using (1) a semi- structured questionnaire to elicit socio-demographic
information and medical data (2) Brief Pain Inventory (3) ICD-10 Symptom
Checklist (4) ICD-10-Diagnostic Criteria for Research (DCR) (5) Montgomery Asberg
Depression Rating Scale (MADRS) (6) Covi Anxiety Rating Scale (7) Karnofsky
Performance Status Scale. Data was analysed using independent sample t test and
chi square test. RESULTS: The psychiatric morbidity was 67% with depression and
adjustment disorders being the major diagnosis. There was a significant
association between psychiatric morbidity pain variables (P = 0.000). Psychiatric
morbidity significantly impaired activity, mood, working, walk, sleep,
relationship, and enjoyment. There was no association between aetiology of pain,
type of cancer, treatment for primary condition and treatment for pain and
psychiatric morbidity. The functional status of cancer patients was also poorer
in patients with psychiatric morbidity (P = 0.008). CONCLUSION: There is a high
prevalence of psychiatric illness in chronic pain patients of any aetiology.
Psychiatric morbidity is associated with increased pain perception, impairment in
activity and poor functional status.
PMID- 24347905
TI - A Prospective, Non-interventional Study of Assessment and Treatment Adequacy of
Pain in the Emergency Department of a Tertiary Care Cancer Hospital.
AB - INTRODUCTION: Pain is the most common reason for emergency department (ED) visits
by the cancer patients. Treatment inconsistency and inadequacy are reported
worldwide in the management of ED pain. We conducted a non-interventional
observational study of 100 patients visiting ED with moderate to severe pain in a
tertiary care cancer center. AIMS: The goal of this study was to describe the
characteristics of pain and its treatment by oncologists in ED. MATERIALS AND
METHODS: Management of 100 adult patients with complaints of moderate to severe
pain was observed by the investigator in ED. Treatment was provided by the
doctors of respective oncological services. Later, patients were interviewed by
the investigator to collect data about the details of their pain and treatment
adequacy. RESULTS: On arrival to ED, about 65% patients reported severe pain,
however no formal pain assessment was performed and no patient received strong
opioids. Poor compliance for prescribed analgesic medications was noted in a
large number of patients (31%), primarily due to suboptimal pain relief and lack
of awareness. Protocol based analgesic treatment was non-existent in ED. Majority
of patients remained in significant pain after 30 min of analgesic administration
and 24% patients could never achieve more than 50% pain relief at the time of
discharge. CONCLUSION: Due to lack of formal pain assessment and laid down
protocols, suboptimal pain management is commonly prevalent in ED. Use of strong
opioids continues to be scarce in management of severe pain. There is a need to
formulate pain management protocols for ED pain.
PMID- 24347906
TI - Evaluation of Socio-demographic Factors for Non-compliance to Treatment in
Locally Advanced Cases of Cancer Cervix in a Rural Medical College Hospital in
India.
AB - INTRODUCTION: Carcinoma cervix is a leading cause of cancer in India. However,
majority of the patients face a problem of not being able to complete the
treatment. AIM: This study was an attempt to find out the important causes of
this non-compliance to treatment in a rural Medical College Hospital where
majority of the cancer cases are of cervical cancer. RESULTS: Out of 144 patients
studied over 2 years 88 cases could not complete the treatment. The study
revealed that due old age 58.33% cases were defaulters, having many children at
home meant a burden to 76.92% cases and 63.89% cases had a problem of not been
able to travel a far distance of more than 100 km from home to hospital for
treatment. CONCLUSION: These were the important factors of non-compliance and
suggested more important than the issues of literacy and poor socio-economic
status.
PMID- 24347907
TI - Physiological and psychosocial stressors among hemodialysis patients in
educational hospitals of northern iran.
AB - BACKGROUND AND AIMS: The hemodialysis (HD) patients are experiencing high
biopsychosocial stress on all levels. Therefore, this study was designed to
survey on physiologic and psychosocial stressors among HD patients in two
educational hospitals of Northern Iran. MATERIALS AND METHODS: This cross
sectional study included 80 HD patients who were referred to Khomeini and Fatemeh
Zahra hospitals in Mazandaran (Northern Iran) during the year 2011. Data were
collected using a demographic information record sheet and Baldree Hemodialysis
Stress Scale. FINDING: THE FOLLOWING PHYSIOLOGIC STRESSORS WERE NOTED: Fatigue
(51.25%), limited time and places for enjoyment (46.25%), and physical activation
limitation (32.5%). Similarly the following psychosocial stressors were observed:
Fistula (58.75%), limitation of drinking water (47.5%), low quality of life
(47.5%), travelling difficulties to the dialysis center (45%), treatment cost
(41.5%), and low life expectancy. The stress level was high in women who were
married, younger, less dialysis vintage, and belonged to a low education level.
CONCLUSION: This study reports that HD patients have with significant physical
and psychosocial problems and they need education, family, and social supports.
PMID- 24347909
TI - Randomized Controlled Trial in Advance Stage Breast Cancer Patients for the
Effectiveness on Stress Marker and Pain through Sudarshan Kriya and Pranayam.
AB - OBJECTIVE: The objective of this study is to examine the effect of a cognitive,
behavioral stress management module of Sudarshan Kriya (SK) and P on levels of
serum cortisol and pain among the women suffering from advanced stage breast
cancer. MATERIALS AND METHODS: Participants (n = 147) were screened and
randomized to receive standard care (n = 69) versus standard along with SK and
Pranayam (P) intervention (n = 78) imparted in one 18 hrs workshop spread during
3 days. Participants were expected to practice it at home 20 min daily as
adjuvant to standard pharmacological treatment for pain. RESULTS: There was a
significant difference in blood cortisol levels after 3 months of practice of SK
and P. Mean blood levels in the intervention arm were 341.2 ng/ml against 549.2
ng/ml in the control arm (P <= 0.002). Pain perception in comparison to control
arm reduced by 3 points in SK and P arm on 0-10 verbal scale of pain. CONCLUSION:
SK and P is an effective intervention in reducing stress and pain among advance
stage patients of breast cancer.
PMID- 24347908
TI - An Exploratory Analysis of Levels of Evidence for Articles Published in Indian
Journal of Palliative Care in the years 2010-2011.
AB - CONTEXT: Indian Journal of Palliative Care (IJPC) provides a comprehensive
multidisciplinary evidence base for an evidence-informed clinical decision
making. AIMS: To analyze the levels of evidence of articles published in IJPC in
the years 2010-2011. SETTINGS AND DESIGN: Systematic review of palliative care
journals. MATERIALS AND METHODS: Systematic review of articles was done and was
scored according to Center for Evidence-Based Medicine levels of evidence into
any of the five grades. The articles were categorized based upon article type,
number of authors, study approach, age focus, population focus, disease focus,
goals of care, domains of care, models of care, and year of publication.
STATISTICAL ANALYSIS USED: All descriptive analysis was done using frequencies
and percentiles, and association between all categorical variables was done using
Chi-square test at 95% confidence interval (CI) using Statistical Package for
Social Sciences (SPSS) version 16 for Windows (SPSS Inc, Chicago, IL). RESULTS:
There was a greater prevalence of low level evidence (level 4: n = 46, 51%; level
5: n = 35, 39%) among the 90 selected articles, and article type (original
articles with higher level of evidence, P = 0.000), article approach (analytical
studies with higher level of evidence, P = 0.000), domains of palliative care
(practice-related studies with higher level of evidence, P = 0.000) and models of
care (biological or psychosocial model with higher level of evidence, P = 0.044)
had a significant association with the grade of levels of evidence. Association
with other factors was not statistically significant (P < 0.05). CONCLUSIONS: The
levels of research evidence for palliative care provided by articles published in
IJPC were predominantly level 4 and level 5, and there is scope for more high
quality evidence to inform palliative care decisions in the developing countries.
PMID- 24347910
TI - Baseline Demographic Profile and General Health Influencing the Post-Radiotherapy
Health Related Quality-of-Life in Women with Gynaecological Malignancy Treated
with Pelvic Irradiation.
AB - BACKGROUND: Cancer specific survival and quality-of-life (QOL) assessment are
important in evaluating cancer treatment outcomes. Baseline demographic profiles
have significant effects on follow-up health related QOL (HRQOL) and affect the
outcome of treatments. MATERIALS AND METHODS: Post-operative gynaecological
cancer patients required adjuvant pelvic radiation enrolled longitudinal
assessment study. Patients had completed the short form-36 (SF-36) questionnaire
before the adjuvant radiotherapy and functional assessments of cancer therapy
general module at 6(th) month's follow-up period to assess the HRQOL. Baseline
variables were race, age, body mass index (BMI), education, marital status, type
of surgery, physical composite scores (PCS) and mental composite scores (MCS)
summary scores of the SF-36. Univariate and multivariate regression analysis used
to determine the influence of these variables on post-radiotherapy HRQOL domains.
RESULTS: Baseline PCS, MCS, age, education and marital status had positively
correlation with post-radiotherapy HRQOL while higher BMI had a negative impact
in univariate analysis. In multivariate regression analysis, education and MCS
had a positive correlation while higher BMI had a negative correlation with HRQOL
domains. CONCLUSION: Enhance our ability to detect demographic variables and
modify those factors and develops new treatment aimed at improving all aspect of
gynaecological cancer including good QOL.
PMID- 24347911
TI - Palliative radiation in primary squamous cell carcinoma of thyroid: a rare case
report.
AB - Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm with
aggressive behavior. Until date, only around 60 cases have been reported in the
literature. Primary treatment of the patient is radical surgery. With optimum
treatment survival is not more than 6 months in this aggressive malignancy.
However in our patient surgery it was not possible because of unresectability of
the mass due to encroachment of major vessels. Hence, we have delivered
radiotherapy alone, with which effective palliation could be achieved and patient
is leading a good quality-of-life for last 1 year.
PMID- 24347912
TI - High-level Evidence Exists for Low-level Laser Therapy on Chemoradiotherapy
induced Oral Mucositis in Cancer Survivors.
PMID- 24347913
TI - Healthcare professionals' fear of death and dying: implications for palliative
care.
PMID- 24347914
TI - Systematic reviews on palliative sedation: what do they tell us?
PMID- 24347916
TI - Rasayans and non-rasayans herbs: Future immunodrug - Targets.
AB - Ayurvedic therapeutics describes vast number of medicinal herbs used as
"Vyadhirodhak Chamatav" that has enlightened the application of herbs used as
corner stone in various diseases especially those modulating the immune system.
Ayurveda literature comprises of rasayana and non-rasayana herbs. Materia Medica
entirely enriched with enormous data of rasayana medicinal herbs acting as
immunomodulators in existence. However, as such there is no specific review of
literature available for non-Rasayana herbs that have immense potential as
immunomodulators. This review article empowers data on non-rasayana medicinal
herbs as promising future target for immunotherapy.
PMID- 24347915
TI - Plants and phytochemicals for Huntington's disease.
AB - Huntington's disease (HD) is a neurodegenerative disorder characterized by
progressive motor dysfunction, including chorea and dystonia, emotional
disturbances, memory, and weight loss. The medium spiny neurons of striatum and
cortex are mainly effected in HD. Various hypotheses, including molecular
genetics, oxidative stress, excitotoxicity, metabolic dysfunction, and
mitochondrial impairment have been proposed to explain the pathogenesis of
neuronal dysfunction and cell death. Despite no treatment is available to fully
stop the progression of the disease, there are treatments available to help
control the chorea. The present review deals with brief pathophysiology of the
disease, plants and phytochemicals that have shown beneficial effects against HD
like symptoms. The literature for the current review was collected using various
databases such as Science direct, Pubmed, Scopus, Sci-finder, Google Scholar, and
Cochrane database with a defined search strategy.
PMID- 24347917
TI - In vitro techniques to assess the proficiency of skin care cosmetic formulations.
AB - Cosmetics comprising either natural or synthetic components are used almost
regularly and universally in different forms to enhance the beauty. The utmost
disclosure of human membrane to sunlight and environmental pollution results in
the exhibition of free radical, that react with deoxyribonucleic acid, proteins
and fatty acids, causation oxidative destruction dysfunction of the antioxidant
system. In skin, the formation of reactive oxygen species leads to skin diseases,
predominantly cutaneous malignancies, immunosuppression, wrinkles, aging, etc.,
The human organism fosters a barrier practice against the destructive action of
free radicals, comprising mostly of vitamins, carotenoids and enzymes. Cosmetic
products are the best option to reduce skin disorders such as hyper pigmentation,
skin aging, skin wrinkling and rough skin texture, etc., Hence in this review, we
conferred various in vitro methods that are used for the development of novel
cosmetic formulation. There is an expanding fascinate employing in vitro
techniques because they are less time consuming, more cost-effective and lessen
the participation of human volunteers.
PMID- 24347918
TI - Natural proteins: Sources, isolation, characterization and applications.
AB - Worldwide, plant protein contributes substantially as a food resource because it
contains essential amino acids for meeting human physiological requirements.
However, many versatile plant proteins are used as medicinal agents as they are
produced by using molecular tools of biotechnology. Proteins can be obtained from
plants, animals and microorganism cells. The abundant economical proteins can be
obtained from plant seeds. These natural proteins are obtained by isolation
procedures depending on the physicochemical properties of proteins. Isolation and
purification of single protein from cells containing mixtures of unrelated
proteins is achievable due to the physical and chemical attributes of proteins.
The following characteristics are unique to each protein: Amino acid composition,
sequence, subunit structures, size, shape, net charge, isoelectric point,
solubility, heat stability and hydrophobicity. Based on these properties, various
methods of isolation exist, like salting out and isoionic precipitation.
Purification of proteins is quiet challenging and, therefore, several approaches
like sodium dodecyl sulfate gel electrophoresis and chromatography are available.
Characterization of proteins can be performed by mass spectrometry/liquid
chromatography-mass spectrometry (LC-MS). The amino acid sequence of a protein
can be detected by using tandem mass spectrometry. In this article, a review has
been made on the sources, isolation, purification and characterization of natural
proteins.
PMID- 24347919
TI - Thymoquinone in the clinical treatment of cancer: Fact or fiction?
AB - Thymoquinone (TQ) is the bioactive phytochemical constituent of the seeds oil of
Nigella sativa. In vitro and in vivo research has thoroughly investigated the
anticancer effects of TQ against several cancer cell lines and animal models. As
a result, a considerable amount of information has been generated from research
thus providing a better understanding of the anti-proliferating activity of this
compound. Therefore, it is appropriate that TQ should move from testing on the
bench to clinical experiments. The purpose of this review is to highlight the
potential of TQ as an anticancer agent and the chances of this compound in the
clinical treatment of cancer, with special attention on breast cancer treatment.
PMID- 24347920
TI - Cholinesterase inhibitors from botanicals.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease, wherein a
progressive loss of cholinergic synapses occurs in hippocampus and neocortex.
Decreased concentration of the neurotransmitter, acetylcholine (ACh), appears to
be critical element in the development of dementia, and the most appropriate
therapeutic approach to treat AD and other form of dementia is to restore
acetylcholine levels by inhibiting both major form of cholinesterase:
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Consequently,
researches have focused their attention towards finding cholinesterase inhibitors
from natural products. A large number of such inhibitors have been isolated from
medicinal plants. This review presents a comprehensive account of the advances in
field of cholinesterase inhibitor phytoconstituents. The structures of some
important phytoconstituents (collected through www.Chemspider.com) are also
presented and the scope for future research is discussed.
PMID- 24347921
TI - Oleandrin: A cardiac glycosides with potent cytotoxicity.
AB - Cardiac glycosides are used in the treatment of congestive heart failure and
arrhythmia. Current trend shows use of some cardiac glycosides in the treatment
of proliferative diseases, which includes cancer. Nerium oleander L. is an
important Chinese folk medicine having well proven cardio protective and
cytotoxic effect. Oleandrin (a toxic cardiac glycoside of N. oleander L.)
inhibits the activity of nuclear factor kappa-light-chain-enhancer of activated B
chain (NF-kappaB) in various cultured cell lines (U937, CaOV3, human epithelial
cells and T cells) as well as it induces programmed cell death in PC3 cell line
culture. The mechanism of action includes improved cellular export of fibroblast
growth factor-2, induction of apoptosis through Fas gene expression in tumor
cells, formation of superoxide radicals that cause tumor cell injury through
mitochondrial disruption, inhibition of interleukin-8 that mediates tumorigenesis
and induction of tumor cell autophagy. The present review focuses the
applicability of oleandrin in cancer treatment and concerned future perspective
in the area.
PMID- 24347922
TI - Onosma L.: A review of phytochemistry and ethnopharmacology.
AB - The genus Onosma L. (Boraginaceae) includes about 150 species distributed world
wide in which only about 75 plants has been described for its morphology and less
than 10 plants for their chemical constituents and clinical potential. The
phytochemical reports of this genus revels that it comprise mainly aliphatic
ketones, lipids, naphthazarins, alkaloids, phenolic compounds, naphthoquinones,
flavones while most important are shikonins and onosmins. The plants are
traditionally used as laxative, anthelmintic and for alexipharmic effects. The
plants are also equally use in eye, blood diseases, bronchitis, abdominal pain,
stangury, thirst, itch, lecoderma, fever, wounds, burns, piles and urinary
calculi. The flowers of various plants are prescribed as stimulants, cardiotonic,
in body swelling while leaves are used as purgative and in cutaneous eruptions.
The roots are used for coloring food stuffs, oils and dying wool and in medicinal
preparations. This review emphasizes the distribution, morphology, phytochemical
constituents, ethnopharmacology, which may help in future research.
PMID- 24347923
TI - Camellia sinensis (Tea): Implications and role in preventing dental decay.
AB - Tea is one of the most commonly consumed beverages with bioactive compounds like
polyphenols-flavonoids-catechins, which are thought to be responsible for the
health benefits that have traditionally been attributed to the tea. These
compounds have multi-dimensional effects such as antibacterial action, inhibitory
action on the bacterial and salivary amylase and inhibition of acid production.
This article outlines the possible role of these compounds coupled with the
presence of high fluoride content in tea to exhibit an anticariogenic effect.
PMID- 24347924
TI - Review on Sphaeranthus indicus Linn. (Kottaikkarantai).
AB - Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known
with other synonyms such as Munditika, Mundi, Shravana, Bhikshu, Tapodhana,
Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in
damp areas in plains and also as a weed in the rice fields. In the Indian system
of medicine, the plant as a whole plant or its different anatomical parts viz.,
leaf, stem, bark, root, flower and seed are widely used for curing many diseases.
The plant is bitter, stomachic, restorative, alterative, pectoral, demulcent and
externally soothing. The whole plant and its anatomical parts have been reported
with different types of secondary metabolites which include eudesmanolides,
sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone
glycosides, flavonoid C-glycosides, isoflavone glycoside, sterols, sterol
glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential
oils obtained from the flowers and whole plants were analyzed by different
authors and reported the presence of many monoterpene hydrocarbons, oxygenated
monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole
plants, its isolated secondary metabolites and different anatomical parts have
been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral,
macrofilaricidal, larvicidal, analgesic, antipyretic, hepatoprotective,
antitussive, wound healing, bronchodilatory, mast cell stabilizing activity,
anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and
antioxidant, antioxidant, central nervous system depressant, anti-arthritic,
nephroprotective, anticonvulsant activities and many other activities. It is also
effective on psoriasis. In the present paper, the plant is reviewed for its
phytochemical and pharmacological reports in detail.
PMID- 24347925
TI - Biological activities and chemical constituents of some mangrove species from
Sundarban estuary: An overview.
AB - This review represents the studies performed on some beneficial mangrove plants
such as Ceriops decandra, Xylocarpus granatum, Xylocarpus moluccensis, Excoecaria
agallocha, Sarcolobus globosus, Sonneratia caseolaris and Acanthus ilicifolius
from the Sundarban estuary spanning India and Bangladesh with regard to their
biological activities and chemical investigations till date. Sundarban is the
largest single chunk of mangrove forest in the world. The forest is a source of
livelihood to numerous people of the region. Several of its plant species have
very large applications in the traditional folk medicine; various parts of these
plants are used by the local people as cure for various ailments. Despite such
enormous potential, remarkably few reports are available on these species
regarding their biological activities and the active principles responsible for
such activities. Though some chemical studies have been made on the mangrove
plants of this estuary, reports pertaining to their activity-structure
relationship are few in number. An attempt has been made in this review to
increase the awareness for the medicinal significance as well as conservation and
utilization of these mangrove species as natural rich sources of novel bioactive
agents.
PMID- 24347926
TI - A review on phytochemistry and ethnopharmacological aspects of genus Calendula.
AB - This review includes 84 references on the genus Calendula (Asteraceae) and
comprises ethnopharmacology, morphology and microscopy, phytoconstituents,
pharmacological reports, clinical studies and toxicology of the prominent species
of Calendula. Triterpene alcohols, triterpene saponins, flavonoids, carotenoids
and polysaccharides constitute major classes of phytoconstituents of the genus. A
few species of this genus have medicinal value, among these Calendula officinalis
Linn., has been traditionally used in the treatment of various skin tumors,
dermatological lesions, ulcers, swellings and nervous disorders as well as almost
200 cosmetic formulations, i.e., creams, lotions, shampoos. Despite a long
tradition of use of some species, the genus has not been explored properly. In
the concluding part, the future scope of Calendula species has been emphasized
with a view to establish their multifarious biological activities and mode of
action.
PMID- 24347927
TI - The genus Vitex: A review.
AB - The review includes 161 references on the genus Vitex, and comprises
ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological
reports, clinical studies, and toxicology of the prominent species of Vitex.
Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans
constitute major classes of phytoconstituents of the genus. A few species of this
genus have medicinal value, among these, leaves and fruits of V. agnus-castus
Linn. (Verbenaceae) has been traditionally used in treatment of women complaints.
V. agnus-castus has also been included in herbal remedies, which are in clinical
use to regulate the menstrual cycle, reduce premenstrual symptom tension and
anxiety, treat some menopausal symptoms as well as to treat hormonally induced
acne. Despite a long tradition of use of some species, the genus has not been
explored properly. In the concluding part, the future scope of Vitex species has
been emphasized with a view to establish their multifarious biological activities
and mode of action.
PMID- 24347929
TI - From the Editor's desk.
PMID- 24347928
TI - Pharmacological and therapeutic effects of Peganum harmala and its main
alkaloids.
AB - Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran
and various parts of this plant including, its seeds, bark, and root have been
used as folk medicine. Recent years of research has demonstrated different
pharmacological and therapeutic effects of P. harmala and its active alkaloids,
especially harmine and harmaline. Analytical studies on the chemical composition
of the plant show that the most important constituents of this plant are beta
carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most
studied among these naturally occurring alkaloids. In addition to P. harmala
(Syrian rue), these beta-carbolines are present in many other plants such as
Banisteria caapi and are used for the treatment of different diseases. This
article reviews the traditional uses and pharmacological effects of total extract
and individual active alkaloids of P. harmala (Syrian rue).
PMID- 24347930
TI - Hyperprolactinemia.
AB - Prolactin (PRL) is an anterior pituitary hormone which has its principle
physiological action in initiation and maintenance of lactation. In human
reproduction, pathological hyperprolactinemia most commonly presents as an
ovulatory disorder and is often associated with secondary amenorrhea or
oligomenorrhea. Galactorrhea, a typical symptom of hyperprolactinemia, occurs in
less than half the cases. Out of the causes of hyperprolactinemia, pituitary
tumors may be responsible for almost 50% of cases and need to be investigated
especially in the absence of history of drug induced hyperprolactinemia. In women
with hyperprolactinemic amenorrhea one important consequence of estrogen
deficiency is osteoporosis, which deserves specific therapeutic consideration.
Problem in diagnosing and treating hyperprolactinemia is the occurrence of the
'big big molecule of prolactin' that is biologically inactive (called
macroprolactinemia), but detected by the same radioimmunoassay as the
biologically active prolactin. This may explain many cases of very high prolactin
levels sometimes found in normally ovulating women and do not require any
treatment. Dopamine agonist is the mainstay of treatment. However, presence of a
pituitary macroadenoma may require surgical or radiological management.
PMID- 24347931
TI - A clinical appraisal of the genetic basis in unexplained male infertility.
AB - Unexplained male infertility (UMI), the inability to reproduce despite having a
normal sexual history, physical exam and semen analysis, can have a genetic
origin. Currently, few diagnostic tools are available for detecting such genetic
abnormalities. Karyotyping and fluorescence in situ hybridization (FISH) are
respectively used for chromosomal alterations in somatic cells and sperm
aneuploidy assessment. Gene sequencing and mutational analysis have been
introduced for identifying specific mutations and polymorphisms. Other approaches
to the molecular evaluation of spermatozoa are under investigation, including
array comparative genomic hybridization and whole-genome sequencing and non
coding ribonucleic acid arrays. Although treating cytogenetic abnormalities and
genetic aberrations is still out of reach, the integration of these novel
techniques may unravel hidden genetic defects in UMI. Finally, a deeper
understanding of the sperm epigenome might allow the development of therapies
based on epigenome modifications. This review focuses on the genetic basis of UMI
and highlights the current and future methods for the evaluation of genetic
defects as they relate to UMI. Review of the literature was carried out using
ScienceDirect, OVID, PubMed and MedLine search engines.
PMID- 24347932
TI - Transfer of spontaneously hatching or hatched blastocyst yields better pregnancy
rates than expanded blastocyst transfer.
AB - CONTEXT: Blastocyst stage embryo transfer (ET) has become routine practice in
recent years. However, probably due to limitations of assisted hatching
techniques, expanded blastocyst transfer (EBT) is still the preferred mode.
Inexplicably, not much consideration has been given to spontaneously
hatching/hatched blastocyst transfer (SHBT). AIM: This study aimed to investigate
developmental potential of spontaneously hatching/hatched blastocyst against EBT
in in vitro fertilization (IVF) cycles. SETTINGS AND DESIGN: Prospective study of
146 women undergoing their first IVF- ET cycle. SUBJECTS AND METHODS: On the
basis of blastocyst status, women were classified into SHBT and EBT groups.
Intracytoplasmic sperm injection cycles were excluded to remove male factor bias.
Implantation rate (IR), clinical pregnancy rate, and live birth rate were the
main outcome measures. STATISTICAL ANALYSIS: Graph-pad Prism 5 statistical
package. RESULTS: SHBT group showed significantly higher blastocyst formation
rate (53.3 +/- 17.5 vs. 43.1 +/- 14.5%, P = 0.0098), top-quality blastocysts
(71.8 vs. 53.7%, P = 0.0436), IR (43.6 vs. 27.9%, P = 0.0408), pregnancy rate
(59.4 vs. 45.1%, P = 0.0173), and live birth rate (36.8 vs. 22.8%, P = 0.003)
compared to EBT group. Multiple pregnancy rates remained comparable between the
two groups. Implantation correlated strongly with top-quality blastocysts
(Pearson, r = 0.4441) in SHBT group, while the correlation was nonsignificant in
EBT group. CONCLUSION: Extending culture of expanded blastocysts by a few hours
to allow transfer of spontaneously hatching/hatched blastocysts gives higher
implantation and pregnancy rates with no added risk of multiple gestations.
Spontaneously hatching/hatched blastocysts have a better potential to implant and
develop into a positive pregnancy.
PMID- 24347933
TI - Ultrasound diagnosis of adenomyosis, leiomyoma, or combined with
histopathological correlation.
AB - OBJECTIVE: To evaluate the accuracy, sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV) of the diagnosis of
adenomyosis, leiomyoma, or combined adenomyosis and leiomyoma by the use of
transvaginal ultrasonography (TVS) compared to the histopathological findings.
SUBJECTS AND METHODS: This is a retrospective study of patients with a
preoperative TVS diagnosis of adenomyosis, leiomyoma, or combined. Patients
diagnosed with adenomyosis or combined adenomyosis and leiomyoma via TVS
underwent hysterectomy. Symptomatic patients diagnosed with adenomyosis and
leiomyoma via TVS underwent myomectomy with excision of the surrounding
myometrium which contained possible adenomyosis. Following surgery, a
histopathological examination was performed by the hospital pathologists. The
microscopic diagnosis of the specimen was recorded. RESULTS: TVS diagnosis of
adenomyosis was sensitive but not specific. TVS was sensitive, specific, and
accurate in the diagnosis of leiomyoma and combined adenomyosis and leiomyoma.
CONCLUSION: This study demonstrated that TVS is a valuable noninvasive method
that should be utilized in the diagnosis of leiomyoma and combined adenomyosis
and leiomyoma. TVS is sensitive, but is not specific in the diagnosis of
adenomyosis only.
PMID- 24347934
TI - Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS
phenotypes: A prospective study of PCOS women.
AB - AIMS: 1. To study the distribution of various Rotterdam classified phenotypes of
polycystic ovarian syndrome (PCOS) women, in our population. 2. To compare the
four phenotypes with respect to anthropometric, clinical, and metabolic
parameters. 3. To report the prevalence of insulin resistance (IR) and metabolic
syndrome in these women. SETTINGS AND DESIGN: Private practice, Prospective cross
sectional comparative study. MATERIALS AND METHODS: Women attending gynecology
outpatient with the primary complains of irregular menses and/or infertility were
evaluated. Each of them underwent detailed clinical examination, transvaginal
sonography, and biochemical and hormonal assays. Four hundred and ten women with
a clinical diagnosis of PCOS based on Rotterdam criteria were included in the
study. The four phenotypes were 1) PCO complete, that is oligo/anovulation (O) +
polycystic ovaries (P) + hyperandrogenism (H) 2) P + O, 3) P + H, and 4) O + H.
All women were also evaluated for metabolic syndrome (American Heart
Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), modified Adult
Treatment Panel (ATP) III 2005 guidelines) and IR (homeostatic model assessment
IR (HOMA-IR)). STATISTICAL ANALYSIS: Statistical Package for Social Sciences
(SPSS) version 18. RESULTS: Largest group was PCOS complete (65.6%) followed by P
+ O (22.2%); H + O (11.2%); and P + H (0.9%). Overall prevalence of metabolic
syndrome was 35.07%. Hyperandrogenic phenotyptes; H + O (50%) and P + H + O
(37.04%), had significantly higher prevalence of metabolic syndrome than
normoandrogenic P + O phenotype (10%) (P <= 0.001). Body mass index (BMI) >= 25
(P = 0.0004; odds ratio (OR) = 3.07 (1.6574-5.7108, 95% CI)), waist circumference
(WC) >= 80 cm (P = 0.001; OR = 3.68 (1.6807-8.0737, 95% CI)) and family history
of diabetes (P = 0.019; OR 1.82 (1.1008-3.0194, 95% CI)), were strongly
associated with the presence of metabolic syndrome. The overall prevalence of IR
in PCOS women was 30.44% (HOMA-IR cutoff >= 3.8) and 34.94% (HOMA-IR cutoff >=
3.5). CONCLUSIONS: The prevalence of metabolic syndrome and IR was 35.07 and
30.44%, respectively. The hyperandrogenic phenotypes have significantly higher
metabolic morbidity compared to normoandrgenic phenotype. BMI > 25, WC >= 80 cm,
and family history of diabetes carry the highest risk for developing metabolic
syndrome.
PMID- 24347935
TI - Impact of socio-economic status on ovarian reserve markers.
AB - BACKGROUND: Fertility rates have started declining in India in the last few
decades. The total fertility rate, which was 3.5 in 93-94 declined to 2.5 in 2005
6. Researchers attribute this fertility transition to concomitant socio-economic
development. Decreasing ovarian reserve is an important contributor for age
related infertility. OBJECTIVES: The objective of this study was to assess the
association of ovarian reserve with socio-economic status (SES) with the
available clinical ovarian reserve markers in reproductive age women. MATERIALS
AND METHODS: A total of 160 married women in the age group of 20-35 years,
belonging to all three socio-economic strata were assessed for ovarian reserve
using the clinical ovarian reserve parameters Antimullerian hormone (AMH), Antral
follicle count (AFC) and follicular stimulating hormone (FSH). Analysis of
variance was used to see the association of ovarian reserve with SES. RESULTS:
Both the ovarian parameters AMH and AFC have shown a significant association with
SES (P = 0.000 for AMH and P = 0.023 for AFC). The association between FSH and
SES was not significant (P = 0.147). CONCLUSIONS: Higher SES in this study was
seen to be associated with better ovarian reserve as assessed by the available
clinical ovarian reserve markers.
PMID- 24347938
TI - Finding relief at the end of the (Carpal) tunnel: Electrophysiological clues.
PMID- 24347937
TI - Role of early serum beta human chorionic gonadotropin measurement in predicting
multiple pregnancy and pregnancy wastage in an in vitro ET fertilization cycle.
AB - OBJECTIVE: This study was performed to assess the prognostic value of serum beta
human chorionic gonadotropin (betahCG), measured on day 14 post embryo transfer
(ET) for predicting multiple gestation and pregnancy wastage in women undergoing
in vitro fertilization ET (IVF-ET). MATERIALS AND METHODS: This retrospective
study was performed between May 2009 and November 2012. Out of the 181 women who
conceived, 168 were included and the remaining 13 were excluded as their
pregnancy was biochemical. Serum betahCG was measured using a chemiluminescent
enzyme immunometric assay. The predictive values of serum betahCG for
establishing multiple pregnancy and pregnancy wastages were calculated by
receiver operating characteristic (ROC) curve analysis. Median values of serum
betahCG and outcome of all pregnancies were compared. RESULTS: Out of the 168
patients who conceived after IVF treatment, 114 (68%) were viable pregnancies
(delivered/ongoing). Among the viable pregnancies, 97 (85%) had a successful
pregnancy outcome and the remaining 17 patients are ongoing pregnancies. Median
values of betahCG (625 IU/L) among viable pregnancies was significantly (P <
0.05) higher than that of nonviable pregnancies (174 IU/L). The median values of
betahCG for singleton (502 IU/L), twins (1093 IU/L), and triplets (2160 IU/L) was
statistically significant (P < 0.05). Using ROC curve it was predicted that for a
value of betahCG at 375 IU/L, the sensitivity of viable pregnancy was 65% and
specificity of viable pregnancy was also 65%, with positive and negative
predictive values of 65 and 68%, respectively. Similarly for multiple pregnancy
and pregnancy wastage the predictive values of betahCG were 808 and 375 IU/L,
respectively; while the sensitivity and specificity is more than 65% each.
CONCLUSION: betahCG cutoff values determined on day 14 post ET by ROC curve
analysis are useful in discriminating between multiple pregnancy and pregnancy
losses. The cutoff value might aid in the prognosis, clinical management, and
counseling of the IVF patients.
PMID- 24347939
TI - Belief and brain.
PMID- 24347936
TI - Comparative multiplex analysis of cytokines, chemokines and growth factors in
follicular fluid of normoresponder women undergoing ovum donation with
gonadotropin-releasing hormone agonist versus gonadotropin-releasing hormone
antagonist protocols.
AB - BACKGROUND: Conflicting results were yielded about the superiority of
gonadotropin-releasing hormone agonist (GnRH-a) versus gonadotropin-releasing
hormone antagonist (GnRH-ant) protocols used in ovarian stimulation in in vitro
fertilization (IVF) set-up. Reports also indicate that any single specific
individual marker in follicular fluid collected at the time of oocyte retrieval
bears inconclusive value as a predictor of oocyte quality. AIMS: Simultaneous
analyses of large numbers of cytokines, chemokines and growth factors in ovarian
follicular fluid and perifollicular vascularity in both protocols for ovarian
stimulation in IVF program to address the above mentioned lacunae. SETTINGS AND
DESIGNS: Normoresponder women (n = 45) were subjected to either GnRH-a (Group 1;
n = 23) or GnRH-ant (Group 2; n = 22) for ovarian stimulation in IVF clinics.
MATERIALS AND METHODS: The fluid samples of dominant follicles collected at
oocyte retrieval from women in Group 1 (GnRH-a; n = 20) and Group 2 (GnRH-ant; n
= 16) were used for simultaneous quantitative assays of 48 cytokines.
Perifollicular vascularity was assessed by Doppler hemodynamics to assess the
ovarian vascular response in all participants in Groups 1 and 2. RESULTS: Despite
demographic and reproductive parameters studied remained comparable, higher
follicular fluid concentration of interleukins, IL-3 (P < 0.01), IL12p70 (P <
0.05) and vascular endothelial growth factor (P < 0.01), P4 (P < 0.05) and
pulsatility index (P < 0.04) along with a lower number of oocytes in metaphase II
stage (P < 0.03) was observed in Group 2 compared with Group 1. GnRH-a protocol
appeared to be superior to GnRH-ant protocol for ovarian stimulation in
normoresponder women.
PMID- 24347940
TI - Cerebral venous and sinus thrombosis.
PMID- 24347941
TI - Etiological beliefs of patients with neurological disorders attending a tertiary
care center: A cross-sectional study.
AB - BACKGROUND: The understanding and management of neurological disorders is
undergoing revolutionary changes over the last three decades in the background of
ever increasing advances in medical technologies, diagnostic techniques,
therapeutic processes and, molecular and genetic medicine. The fruits of these
advances can reach patients only if the psychosocial hurdles in their delivery
are identified, acknowledged and addressed. AIM: To explore the beliefs and
practices of patients with neurological disorders in a tertiary care center in
the eastern Nepal. MATERIALS AND METHODS: One hundred patients attending
neurology/medicine outpatient for neurological disorders were interviewed about
their beliefs regarding the triggering factors, causation and treatment-seeking
behavior particularly from traditional healers. RESULT: Of the 100 patients (49
males, 51 females) recruited in the study, 51% expressed having 'no idea' about
their illness. Only 20% patients gave medically congruent explanation for their
illness. Psychological factors were attributed as triggering factors by 16% of
patients, of which two-thirds were females. Chance, destiny and 'jadu tona'
topped the list of triggering factors. Forty-four percent patients had sought
help of traditional faith healers ('Dhami Jhakri') before seeking medical help.
Traditional faith healers were approached by patients irrespective of their
educational background. Fifty-nine percent of patients who first sought
traditional faith healers, believed in 'jadu-tona'. Of those interviewed, 16%
were planning to go to a faith healer in near future. CONCLUSION: The beliefs of
patients with neurological disorders frequently do not conform to current medical
opinion. There is need for greater communication and education of patients by
their treating physicians.
PMID- 24347942
TI - Depression and sleep disturbances in patients with multiple sclerosis and
correlation with associated fatigue.
AB - OBJECTIVE: To observe prevalence of depression and sleep disturbances in multiple
sclerosis (MS) patients and their correlation with associated fatigue. STUDY
DESIGN AND SETTING: Prospective observation study in a university tertiary
research hospital in India. MATERIALS AND METHODS: Thirty-one patients (6 male
and 25 female) with definite MS (McDonald's criteria) presented in out
patient/admitted in the department of neurology (between February 2010 and
December 2011) were included in the study. Depression was assessed using Beck's
Depression Inventory (BDI). Sleep quality was assessed using Pittsburg Sleep
Quality Index (PSQI). Disease severity was evaluated using the Kurtzke's expanded
disability status scale (EDSS). Fatigue was assessed using Krupp's fatigue
severity scale (FSS). We tried to observe correlation of depression and sleep
disturbance with associated fatigue in MS patients. RESULTS: The age of patients
varied between 16 and 50 years (30.1 +/- 9.1). The mean age at first symptom was
25.2 +/- 6.4 years (range 14-39 years). The prevalence of sleep disturbance and
depression was 51.6% (16/31) each and fatigue 58.1% (18/31) in the study group.
The PSQI scores were significantly greater in the patients with fatigue as
compared with those without fatigue indicating poorer sleep quality is associated
with fatigue in MS (P = 0.005). The BDI scores were also significantly higher in
the fatigue group showing that severity of depression also strongly correlated
with fatigue (P = 0.001). CONCLUSIONS: Depression and sleep disturbance in
patients with MS is significantly correlated with associated fatigue.
PMID- 24347943
TI - Reliability of motor parameters for follow-up after local steroid injection in
carpal tunnel syndrome.
AB - BACKGROUND: Local steroid injection is one of the treatment modalities for carpal
tunnel syndrome (CTS). Symptomatic and electrophysiological improvement has been
previously documented. The electrophysiological parameter, which represents the
most consistent change after local steroid injection, is not well-known.
OBJECTIVE: The objective of this study was to evaluate the changes in
electrophysiological parameters 1 month after local steroid injection and to
determine the parameter that is able to depict improvement across the severity
spectrum of CTS. MATERIALS AND METHODS: Forty-seven patients (27 with bilateral
disease, 74 hands totally) were included. The electrophysiological parameters
studied at baseline included sensory onset latency, sensory nerve action
potential amplitude, sensory conduction velocity (CV), distal motor latency,
compound muscle action potential amplitude and motor CV. All patients were
injected with 40 mg triamcinalone at the wrist. After 1 month, symptomatic
improvement from baseline was documented using visual analog score of 100.
Electrophysiology was repeated. Paired t tests were done between baseline
electrophysiology parameters and those obtained 1 month after steroid injection
for significant improvement. Subgroup analyses were performed in hands with mild
to moderate (Grade 3 or less by Bland's classification) and severe disease
(Grades 4 and 5). RESULTS: All patients showed a symptomatic improvement. Distal
motor latency showed most consistent improvement irrespective of the severity of
CTS. In mild to moderate CTS (Grade 3 or less of the classification given by
Bland) sensory parameters were recordable and showed significant improvement in
addition to distal motor latency. In the subcategory of severe CTS (Grades 4 and
5 of Bland) where sensory parameters are not recordable distal motor latency and
the motor CV showed a significant improvement. CONCLUSION: One month after local
steroid injection among the electrophysiological parameters studied distal motor
latencies showed most consistent and recordable improvement across the severity
spectrum of CTS. This can be used as a single objective parameter to follow-up
patients after a local steroid injection to document improvement or relapse. They
can also be considered as objective parameter to follow-up patients after
surgery.
PMID- 24347944
TI - Commentary.
PMID- 24347945
TI - Commentary.
PMID- 24347946
TI - Nursing students' attitude towards suicide attempters: A study from rural part of
Northern India.
AB - CONTEXT: Majority of health professionals have unfavorable attitudes towards
patients presenting with self-harm, which further compromises their willingness
and outcome of care. AIMS: To assess the nursing students' attitudes toward
suicide attempters. SETTINGS AND DESIGN: Cross-sectional study was conducted in
two nursing colleges of north India. MATERIAL AND METHODS: Three hundred and
eight nursing students were recruited through total enumeration method from May
to June 2012. 'Suicide opinion questionnaire' was administered to assess their
attitudes towards suicide attempters. STATISTICAL ANALYSIS USED: Descriptive
statistics was employed with Statistical Package for Social Sciences version 14.0
for Windows. RESULTS: Majority were single females, from urban locality, with the
mean age of 20 years. Only minority had previous exposure to suicide prevention
programs and management of such cases. Majority of students agreed for mental
illness, disturbed family life, and depression as major push to attempt suicide.
They held favorable attitude for half of the attitudinal statement, but they were
uncertain for rest half of the statements. CONCLUSIONS: They generally had
favorable attitude towards suicide attempters. Their uncertain response
highlights the need for enhancing educational exposure of nursing students and
new staff at the earliest opportunity, to carve their favorable attitude towards
patients presenting with self-harm.
PMID- 24347947
TI - Intelligence quotient is associated with epilepsy in children with intellectual
disability in India.
AB - BACKGROUND: Epilepsy is a disorder that is commonly found in people with
intellectual disability (ID). The prevalence of epilepsy increases with the
severity of ID. The objective of this study was to determine if there is an
association between intelligence quotient (IQ) and epilepsy in children with ID.
MATERIALS AND METHODS: A total of 262 children, aged 3-18 years, with ID were
identified as part of a community-based rehabilitation project. These children
were examined for epilepsy and diagnosed by a psychiatrist and physicians based
on results of electroencephalogram tests. A Spearman's correlation (rho) was used
to determine if there was an association between IQ scores and the occurrence of
epilepsy. X(2) statistics used to examine the relationship of epilepsy with
gender, socioeconomic status, population type, severity of ID, family history of
mental illness, mental retardation, epilepsy, and coexisting disorder. RESULTS:
Spearman's rho -0.605 demonstrates inverse association of IQ with epilepsy. X(2)
demonstrates statistically significant association (P < 0.05) with gender,
severity of ID, cerebral palsy, behavior problems, and family history of mental
illness, mental retardation, and epilepsy. CONCLUSIONS: Lower IQ score in
children with ID has association with occurrence of epilepsy. Epilepsy is also
found highly associated with male gender and lower age.
PMID- 24347948
TI - What is next after transfer of care from hospital to home for stroke patients?
Evaluation of a community stroke care service based in a primary care clinic.
AB - CONTEXT: Poststroke care in developing countries is inundated with poor
concordance and scarce specialist stroke care providers. A primary care-driven
health service is an option to ensure optimal care to poststroke patients
residing at home in the community. AIMS: We assessed outcomes of a pilot long
term stroke care clinic which combined secondary prevention and rehabilitation at
community level. SETTINGS AND DESIGN: A prospective observational study of stroke
patients treated between 2008 and 2010 at a primary care teaching facility.
SUBJECTS AND METHODS: Analysis of patients was done at initial contact and at 1
year post treatment. Clinical outcomes included stroke risk factor(s) control,
depression according to Patient Health Questionnaire (PHQ9), and level of
independence using Barthel Index (BI). STATISTICAL ANALYSIS USED: Differences in
means between baseline and post treatment were compared using paired t-tests or
Wilcoxon-signed rank test. Significance level was set at 0.05. RESULTS: Ninety
one patients were analyzed. Their mean age was 62.9 [standard deviation (SD)
10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between
acute stroke and first contact with the clinic 4.0 (interquartile range 9.0)
months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007),
while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P =
0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median
BI increased from 81 (range: 2-100) to 90.5 (range: 27-100) (Z = 2.34, P = 0.01).
Median PHQ9 scores decreased from 4.0 (range: 0-22) to 3.0 (range: 0-19) though
the change was not significant (Z= -0.744, P = 0.457). CONCLUSIONS: Primary care
driven long-term stroke care services yield favorable outcomes for blood pressure
control and functional level.
PMID- 24347949
TI - The "Skull Flap" a new conceived device for decompressive craniectomy
experimental study on dogs to evaluate the safety and efficacy in reducing
intracranial pressure and subsequent impact on brain perfusion.
AB - BACKGROUND: Decompressive craniectomy (DC) is a procedure performed increasingly
often in current neurosurgical practice. Significant perioperative morbidity may
be associated to this procedure because of the large skull defect; also, later
closure of the skull defect (cranioplasty) may be associated to post-operative
morbidity as much as any other reconstructive operation. The authors present a
newly conceived/developed device: The "Skull Flap" (SF). This system, placed at
the time of the craniectomy, offers the possibility to provide cranial
reconstruction sparing patients a second operation. In other words, DC and
cranioplasty essentially take place at the same time and in addition, patients
retain their own bone flap. The current study conducted on animal models,
represents the logical continuation of a prior recent study, realized on cadaver
specimens, to assess the efficacy and safety of this recently developed device.
MATERIALS AND METHODS: This is an experimental pilot study on dogs to assess both
safety and efficacy of the SF device. Two groups of experimental raised
intracranial pressure animal models underwent DC; in the first group of dogs, the
bone flap was left in raised position above the skull defect using the SF device;
on the second group the flap was discarded. All dogs underwent transcranial
Doppler (TCD) to assess brain perfusion. Head computed tomography (CT) scan to
determine flap position was also obtained in the group in which the SF device was
placed. RESULTS: SF has proved to be a strong fixation device that allows
satisfactory brain decompression by keeping the bone flap elevated from the
swollen brain; later on, the SF allows cranial reconstruction in a simple way
without requiring a second staged operation. In addition, it is relevant to note
that brain perfusion was measured and found to be better in the group receiving
the SF (while the flap being in a raised as well as in its natural position)
comparing to the other group. CONCLUSION: The SF device has proved to be very
easy to place, well-adaptable to a different type of flaps and ultimately very
effective in maintaining satisfactory brain decompression and later on, making
easy bone flap repositioning after brain swelling has subsided.
PMID- 24347951
TI - Kummell's disease - uncommon or underreported disease: A clinicopathological
account of a case and review of literature.
AB - Kummell's disease is a rare form of vertebral body osteonecrosis, which develops
as a delayed post-traumatic event. It is infrequently reported in literature and
to the best of our knowledge, has not been reported from India. We describe the
clinical, radiological, and pathological features of a case occurring in a 60
year-old man and relevant brief review of the literature of this rare disease.
Its close resemblance to more commonly occurring bony tuberculosis poses a
diagnostic dilemma particularly in developing country like India, where
tuberculosis is endemic. Awareness of this entity, though rare, is essential to
avoid unnecessary diagnostic work up and treatment.
PMID- 24347952
TI - Commentary.
PMID- 24347950
TI - Cerebral sinus venous thrombosis.
AB - Cerebral sinus venous thrombosis (CSVT) is a rare phenomenon that can be seen
with some frequency in young patients. CSVT is a multifactorial condition with
gender-related specific causes, with a wide clinical presentation, the leading
causes differ between developed and developing countries, converting CSVT in a
condition characterized by a highly variable clinical spectra, difficult
diagnosis, variable etiologies and prognosis that requires fine medical skills
and a high suspicious index. Patients who presents with CSVT should underwent to
CT-scan venography (CVT) and to the proper inquiry of the generating cause. This
disease can affect the cerebral venous drainage and related anatomical structure.
The symptoms may appear in relation to increased intracranial pressure imitating
a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the
cause, generally the complications can be prevented. Mortality trends have
diminished, and with the new technologies, surely it will continue. This work
aims to review current knowledge about CSVT including its pathogenesis, etiology,
clinical manifestations, diagnosis, and treatment.
PMID- 24347953
TI - Commentary.
PMID- 24347954
TI - A case of multiple myeloma presenting as scalp swelling with intracranial
extension.
AB - Multiple myeloma is a malignant neoplasm of bone marrow affecting plasma cells.
It is usually detected in skull bone with characteristic features of multiple
punched-out lesions. Its presentation as a solitary scalp swelling with
underlying skull bone erosion and intracranial extension is very rare. A 35-year
old female presented to us with complains of rapidly growing left-side scalp
swelling with right-side paresis and simple partial seizure of right upper limb.
Local examination, X-ray skull, CT scan, and MRI of brain were suggestive of a
malignant lesion. Near total excision of lesion was done. Histopathological study
was suggestive of plasmacytoma of skull. Bone marrow study further confirmed it
as a case of multiple myeloma. Cases presenting with solitary osteolytic skull
lesions, possibility of plasmacytoma, or multiple myeloma should be kept in mind.
PMID- 24347955
TI - Commentary.
PMID- 24347956
TI - Late onset of atypical paroxysmal non-kinesigenic dyskinesia with remote history
of Graves' disease.
AB - Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare hyperkinetic movement
disorder and falls under the category of paroxysmal movement disorders. In this
condition, episodes are spontaneous, involuntary, and involve dystonic posturing
with choreic and ballistic movements. Attacks last for minutes to hours and
rarely occur more than once per day. Attacks are not typically triggered by
sudden movement, but may be brought on by alcohol, caffeine, stress, fatigue, or
chocolate. We report a patient with multiple atypical features of PNKD. She had a
7-year history of this condition with onset at the age of 59, and a remote
history of Graves' disease requiring total thyroidectomy. The frequency of
attacks in our case ranged from five to six times a day to a minimum of twice per
week, and the duration of episode was short, lasting not more than 2 min.
Typically, PNKDs occur at a much younger age and have longer attack durations
with low frequency. Administering clonazepam worked to reduce her symptoms,
although majority of previous research suggests that pharmacological
interventions have poor outcomes.
PMID- 24347957
TI - Commentary.
PMID- 24347958
TI - Giant cystic intradural extramedullary pilocytic astrocytoma of Cauda equina.
AB - Astrocytomas of Conus-Cauda equina region are rare. Astrocytomas, which are
intramedullary tumors, may rarely have an extramedullary component. However,
primary intradural extramedullary astrocytomas are extremely rare, with very few
cases reported in the literature. We describe a giant extramedullary pilocytic
astrocytoma of Cauda equina in a 20-year-old male. To the best of our knowledge,
this is the first report of such a case in the available literature. This case
highlights the fact that astrocytomas can be primarily extramedullary and
emphasizes the need to consider pilocytic astrocytoma in the differential
diagnosis of cystic Cauda equina tumors.
PMID- 24347959
TI - Posterior approach for giant S1 neurofibroma in Von Recklinghausen's disease: Is
total resection realistic?
AB - Bilateral sacral neurofibromas are uncommonly seen in neurofibromatosis type 1
(NF1) also known as Von Recklinghausen's disease. They often grow to enormous
dimensions before detection owing to bone scalloping. Resections of "giant" S1
neurofibromas are difficult due to the limitations of operative window in sacrum
and critical functions associated with S1 nerve root. We report a case of
bilateral S1 neurofibromas in a patient of NF1 where she had a giant left-sided
neurofibroma with extensive bone erosion and a small fusiform neurofibroma on the
right side. The tumor was excised completely on the left and near totally on the
right side via posterior approach. There were no postoperative neurological
deficits and the patient recovered well. Usually, complete excision harbors the
chances of postoperative neurological deficits due to the eloquence of the nerve
root involved and complete resection without significant morbidity seems
unrealistic. However, excision of giant ones may not result in grave deficits
always if the patient is neurologically intact before surgery. Also, in selected
patients, only posterior approach may suffice for giant neurofibromas with
extensive bone scalloping and complete removal can be attempted successfully
despite narrow corridors.
PMID- 24347960
TI - Commentary.
PMID- 24347961
TI - Disseminated neurocysticercosis presenting as affective mood disorder with
chronic tension type headache.
AB - Neurocysticercosis is a common parasitic infection in India presenting usually
with seizues, headache, focal neurological deficits. Neurocysticercosis
presenting as a psychiatric illness is rare. Disseminated cysticercosis with
involvement of central nervous system and head and neck muscles is rare even in
endemic areas. We present a case of disseminated cysticercosis, which presented
with chronic tension type headache and affective mood disorder. Treatment with
cysticidal drugs led to complete remission of psychiatric complaints. In endemic
areas history suggestive of mood disorder should not be used as supportive
evidence of a primary headache syndome like tension type headche without ruling
out secondary causes. Making an early diagnosis can prevent morbidity.
PMID- 24347962
TI - Vitamin D deficiency rickets presenting as pseudotumor cerebri.
AB - Pseudotumor cerebri is a condition of elevated intracranial pressure in the
absence of clinical, laboratory or radiological evidence of an intracranial space
occupying lesion. Various associations with pseudotumor cerebri have been made in
literature. We report the case of a five-month-old female infant with vitamin D
deficiency rickets, who presented with pseudotumor cerebri. Her cerebrospinal
fluid examination was normal, with a high opening pressure of 330 mmH2O. Her
computed tomography scan was normal. After lumbar puncture the anterior
fontanelle came at level. Her investigations revealed vitamin D deficiency. She
was started on acetazolamide, calcitriol sachets, and calcium supplements. She
became asymptomatic in three days and was discharged. Through this case we wish
to highlight this unusual presentation of vitamin D deficiency rickets appearing
as pseudotumor cerebri.
PMID- 24347963
TI - Acute traumatic orbital encephalocele: A case report with review of literature.
AB - Orbital roof fractures after a blunt injury are an uncommon complication of
trauma. Traumatic encephaloceles in the orbital cavity are even rarer, with only
15 cases published till date. Raised intraorbital pressure leading to
irreversible damage to the optic nerve can be prevented by early diagnosis and
management. Orbital computed tomography (CT) with thin axial and coronal sections
is helpful in trauma patients with a concurrent orbital trauma. Decompression of
the orbital roof is the key step in surgical treatment and should be performed in
every case. Repairing the orbital roof has to be performed to avoid transmission
of variation in the intracranial pressure to the orbit. We present a case of
traumatic orbital encephalocele who underwent surgical treatment via a
frontobasal approach with evacuation of the contused herniated brain and
reconstruction of the orbital roof using temporalis fascia which is readily
available in contrast to costly materials like titanium mesh, screws, bone
powder, fibrin glue, and so on, which are not easily available in every hospital.
Rapid resolution of proptosis and visual symptoms along with excellent cosmetic
outcome was seen at follow-ups after three and nine months. We emphasize the
early diagnosis of this rare condition and also emergency treatment to prevent
permanent visual loss as well as to achieve good cosmetic results.
PMID- 24347964
TI - Using the head as a mould for cranioplasty with methylmethacrylate.
AB - Methacrylate is a valuable tool to the neurosurgeon, even though it is currently
being replaced by custom bone. During cranioplasty in the absence of custom bone,
which is preformed based on the patients imaging, one has to make a cast to cover
the cranial defect with or without the use of a mould. A good artificial skull
outline is necessary for prevention of implant extrusion and acceptable cosmetic
outcome. Using the patients head as a mould is a simple, cheap, and useful
technique. An incision is made, and either a craniectomy or an attempt at skull
elevation or separation of the scalp from dura is done based on the indication
for the cranioplasty. The methacrylate monomer is mixed with its solvent. It is
placed in between a sliced glove and then thinned out. Several layers of drapes
are placed on the patients head, the acrylate which is in between the gloves is
then placed on the drapes. As soon as it starts setting and the required shape
obtained, it is removed and place on the sterile tray. It is then anchored and
the wound closed. This technique produces good cosmetic outcome. However, the
head must be properly protected from the risk of burns from the exothermic
reaction. The technique is described in a 40-year-old driver who had a compound
depressed skull fracture. He had a methylmethacrylate cranioplasty in the 9(th)
week post trauma after allowing for wound healing. We recommend that this
technique may be used in centers where custom bone is either too expensive or not
available during cranioplasty in order to obtain a good outcome.
PMID- 24347965
TI - Erratum.
PMID- 24347966
TI - Reduction in global burden of stroke in underserved areas.
PMID- 24347967
TI - Bilateral cystic glioblastoma multiforme.
PMID- 24347968
TI - Ethylene glycol toxic encephalopathy.
PMID- 24347969
TI - Commentary.
PMID- 24347970
TI - Parasympathetic overactivity: A manifestation of temporal lobe epilepsy.
PMID- 24347971
TI - Injection nerve palsy: What's to blame?
PMID- 24347972
TI - Author's response.
PMID- 24347973
TI - Pharmacovigilance in Calabria (Italy): Local experiences resonate international
relevance.
PMID- 24347974
TI - Vertigo/dizziness as a Drugs' adverse reaction.
AB - INTRODUCTION: Vertigo, dizziness, and nausea encompass a spectrum of balance
related symptoms caused by a variety of etiologies. Balance is affected by many
systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and
vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a
subject, as a result to a dysfunction of the vestibular system, improperly
experiments the perception of motion. The most useful clinical subdivision is to
categorize vertigo into true vertigo and pseudovertigo, whereas from a
pathophysiological point of view, vertigo can be classified into central,
peripheral, and psychogenic. It is not easy to identify the cause of vertigo
since the patients often are not able to precisely describe their symptoms. An
impressive list of drugs may cause vertigo or dizziness. MATERIALS AND METHODS:
The aim of the present study was to analyze the data extracted from the reporting
cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance
Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the
occurrence of vertigo and dizziness, after taking certain classes of drugs, have
been considered. RESULTS: Our results show that, among the side-effects of
different classes of drugs such as anti-convulsants, anti-hypertensives,
antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also
vertigo or dizziness are included. CONCLUSIONS: Spontaneous reports of vertigo or
dizziness, as side-effect of certain drugs, received at our Pharmacovigilance
Center, represented the 5% of all reports in 2012. Considering the high incidence
of such an ADR for several drugs' classes, it can be speculated that under
reporting also affect vertigo and dizziness. Despite the fact that these ADRs
might not represent a direct threaten for life, indirectly they can cause
secondary damage to patients such as falls, fractures etc. Balance should be
accurately monitored during drug use and particularly in fragile patients.
PMID- 24347975
TI - Safety and efficacy of generic drugs with respect to brand formulation.
AB - Generic drugs are equivalent to the brand formulation if they have the same
active substance, the same pharmaceutical form and the same therapeutic
indications and a similar bioequivalence respect to the reference medicinal
product. The use of generic drugs is indicated from many countries in order to
reduce medication price. However some points, such as bioequivalence and the role
of excipients, may be clarified regarding the clinical efficacy and safety during
the switch from brand to generic formulations. In conclusion, the use of generic
drugs could be related with an increased days of disease (time to relapse) or
might lead to a therapeutic failure; on the other hand, a higher drug
concentration might expose patients to an increased risk of dose-dependent side
effects.
PMID- 24347976
TI - Pharmacovigilance in Italy: An overview.
AB - INTRODUCTION: Spontaneous reporting of adverse drug reactions (ADRs) is the basis
of pharmacovigilance. In fact, ADRs are associated with a high degree of
morbidity and mortality. However, underreporting by all healthcare professionals
remains the major problem in Italy and in the rest of the world. The
dissemination of pharmacovigilance knowledge among Italian healthcare
professionals, and the new pharmacovigilance regulations may promote the early
detection and reporting of ADRs. This review examines the legislative framework
concerning the pharmacovigilance in Italy. MATERIALS AND METHODS: The information
was collected from scientific articles and the websites of the Italian Ministry
of Health and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA).
RESULTS: The pharmacovigilance system, both in Italy and Europe, has undergone
profound changes. European legislation on pharmacovigilance has been changed in
2010 according to the EU Regulation 1235/2010 and Directive 2010/84/EU.
Basically, the changes tend to increase the efficiency, speed and transparency of
pharmacovigilance activities. The new Regulation (1235/2010) and the Directive
(2010/84/EU) aim to strengthen the system of pharmacovigilance, establish more
precisely who is obliged to do what, and allow faster and easier circulation and
retrieval of information about ADRs. CONCLUSION: A greater knowledge on what is
the Italian pharmacovigilance legislation will be useful to improve the status of
ADRs reporting and spread the culture of spontaneous reporting.
PMID- 24347977
TI - Abatacept in psoriatic arthritis: Case report and short review.
AB - Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about 6-10%
of patients with cutaneous psoriasis. According to current knowledge, activated T
cells seem to play a pivotal role in the pathogenesis of both psoriasis and PsA.
Abatacept is a novel biologic agent selectively designed to interfere with T
cells co-stimulation. Structurally, it is a soluble, fully human fusion protein
consisting of the extracellular domain of CTLA-4 (Cytotoxic T-Lymphocyte Antigen
4) linked to a modified Fc portion of human IgG1. Abatacept is now approved as a
first-line treatment for rheumatoid arthritis (RA), but preliminary data disclose
a potential role of abatacept in the treatment of other autoimmune diseases. In
this article, we report a case of successful treatment with abatacept of a
psoriatic arthritis patients who developed adverse drug reactions (ADRs) to
medication commonly used in PsA, including three different anti-TNF-alpha agents.
In addition, we review the scientific evidences supporting a possible role of
abatacept in treatment of patients with psoriasis and PsA and the paradox of
abatacept-induced psoriasis.
PMID- 24347978
TI - Pharmacovigilance in pharmaceutical companies: An overview.
AB - Pharmacovigilance is responsible for monitoring the safety of medicines in normal
clinical use and during clinical trials. In the light of the experience acquired
and following an assessment by the Commission of the Union system of
pharmacovigilance, it has become clear that it is necessary to take measures in
order to improve the operation of Union law on the pharmacovigilance of medicinal
products for human use. Regulation (EU) No 1235/2010 and Directive 2010/84/EU
introduced new legislation on pharmacovigilance. The marketing authorization
holder should be responsible for continuously monitoring the safety of its
medicinal products for human use, for informing the authorities of any changes
that might have an impact on the marketing authorization, and for ensuring that
the product information is kept up-to-date. Marketing authorization holders (MAH)
record all suspected adverse reactions occurring in the European Union or in the
third countries, and which are brought to their attention spontaneously by the
patients or their health care, or occurring in the context of post-authorization
study. For all medicinal products is mandatory to maintain a pharmacovigilance
system master file (PSMF). According to the Legislative Decree 219/2006 the MAH
must submit to the competent authorities the information on suspected adverse
reactions of a medicinal product, in form of a periodic safety update reports
(PSURs).
PMID- 24347979
TI - Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic
diseases.
AB - Macular degeneration is the leading cause of blindness in developed countries. In
the treatment of neovascular age-related macular degeneration, vascular
endothelial growth factor (VEGF) has emerged as a key target for therapy. The
intravitreal injection of anti-VEGF drugs has been widely employed to reduce the
disease progression and improve the visual outcomes of the affected patients.
However, each intravitreal inoculation poses a risk of several complications as
infection, inflammation, endophthalmitis, intraocular inflammation, increase of
intraocular pressure and vitreous hemorrhage. This short review evaluates the
efficacy and the incidence of adverse drug reactions related to intravitreal
administration of the main anti-VEGF drugs actually available: Bevacizumab,
ranibizumab and aflibercept.
PMID- 24347980
TI - Pharmacovigilance and the italian medicines agency.
AB - The new European Union (EU) regulations on pharmacovigilance require that the
national systems are strengthened in order to fit the new requirements. The
Italian Pharmacovigilance System, coordinated by the Italian Medicines Agency
(AIFA), is made by local and regional structures. In 2007, a program for funding
active pharmacovigilance projects in the Italian Regions was established by the
National law. The AIFA is responsible for the preparation of guidelines aimed at
the identification of research areas and for the approval of the projects
submitted by the regions. In April 2012, the AIFA started a program of visits at
the regional pharmacovigilance centers (RPCs), aimed at monitoring their
performances, evaluating the quality of the activities in order to understand the
main differences and discrepancies and with a view to start a program of
harmonization of the procedures in place. The outcome of the visits program
highlighted major differences among the quality management systems of the various
centers; hence, AIFA has decided to launch an initiative to promote in the next
months the harmonization of procedures. The synergy among AIFA, regional
structures, RPCs, and local structure responsible for pharmacovigilance is needed
in order to establish a robust pharmacovigilance system working in full
compliance with the provisions of the new EU legislation.
PMID- 24347981
TI - Informatics applied to pharmacovigilance: Future perspectives.
AB - Spontaneous adverse drugs reaction (ADRs) reporting represents a precious
resource for control and information about the drug's safety and
pharmacovigilance. The current reporting system is mainly based on handwritten
forms and later manually loaded into a national electronic database by few local
pharmacovigilance centers. This reporting system is complicated for both
reporters and pharmacovigilance centers which often avoid reporting ADRs for
several reasons such as the lack of data on the report. The reporting system
might be implemented by improving online platform for ADRs upload; this could
allow inspecting all ADRs loaded. Currently, the database is only accessible by
the Italian Medicine Agency (AIFA) and local pharmacovigilance centers; neither
reporters nor other healthcare professionals can access the database. Finally, it
would be right to implement pharmacovigilance centers with specific professional
figures qualified in the pharmacovigilance to support both citizens and reporters
on various aspects of ADRs reporting.
PMID- 24347982
TI - Retrospective evaluation of adverse drug reactions induced by antihypertensive
treatment.
AB - The use of cardiovascular drugs is related to the development of adverse drug
reactions (ADRs) in about 24% of the patients in the Cardiovascular Care Unit.
Here, we evaluated the ADRs in patients treated with antihypertensive drugs. The
study was conducted in two phases: In the first phase, we performed a
retrospective study on clinical records of Clinical Divisions (i.e., Internal
Medicine Operative Unit and Geriatric Operative Unit) from January 1, 2012 to
December 31, 2012. Moreover from January 1, 2013 to March 30, 2013 we performed a
prospective study on the outpatients attending the Emergency Department (ED) of
the Pugliese-Ciaccio Hospital of Catanzaro, by conducting patient interviews
after their informed consent was obtained. The association between a drug and ADR
was evaluated using the Naranjo scale. We recorded 72 ADRs in the Clinical
Divisions and six in the ED, and these were more frequent in women. Using the
Naranjo score, we showed a probable association in 92% of these reactions and a
possible association in 8%. The most vulnerable age group involved in ADRs was
that of the elderly patients. In conclusion, our results indicate that
antihypertensive drugs may be able to induce the development of ADRs,
particularly in elderly women receiving multiple drug treatment. Therefore, it is
important to motivate the healthcare providers to understand their role and
responsibility in the detection, management, documentation, and reporting of
ADRs, as also all the essential activities for optimizing patient safety.
PMID- 24347983
TI - A questionnaire-based study in Calabria on the knowledge of off-label drugs in
pediatrics.
AB - Off-label use is very common among pediatricians, and the main cause is
attributable to the lack of drugs specifically designed and marketed for children
in different age groups. In this study, we evaluated, through a questionnaire,
the knowledge of off-label drugs in pediatrics. Furthermore, we made a directory
of 28 off-label drugs most commonly used by pediatricians in agreement with data
obtained from Italian Agency for drugs (AIFA) referred to the law no. 648/1996;
180 pediatricians referred to the Italian Society of Pediatrics Calabrian section
were asked to complete an online anonymous questionnaire. Eighty five (47.3%) of
these completed the anonymous questionnaire, 40% revealed that they used off
label drugs "sometimes"; generally, drugs were used off-label for age and to
treat respiratory diseases. For 75 pediatricians (88%) the information about the
risk/benefit of off-label drugs is inadequate and 63 pediatricians (74%) did not
have a good knowledge about this practice. In conclusion, the knowledge of off
label drugs is very low in pediatricians; more information about off-label drugs
could be useful in order to improve the appropriateness of drugs' prescription
and to reduce the development of side effects and improving drug safety.
PMID- 24347984
TI - Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events
analysis.
AB - INTRODUCTION: Pharmacovigilance (PV) is designed to monitor drugs continuously
after their commercialization, assessing and improving their safety profile. The
main objective is to increase the spontaneous reporting of adverse drug reactions
(ADRs), in order to have a wide variety of information. The Italian Drug Agency
(Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase
reporting. In Calabria, a PV information center has been created in 2010.
MATERIALS AND METHODS: We obtained data using the database of the National Health
Information System AIFA relatively to Italy and Calabria in the year 2012.
Descriptive statistics were performed to analyze the ADRs. RESULTS: A total
number of 461 ADRs have been reported in the year 2012 with an increase of 234%
compared with 2011 (138 reports). Hospital doctors are the main source of this
reporting (51.62%). Sorafenib (Nexavar((r))), the combination of
amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently
reported causing adverse reactions. Adverse events in female patients (61.83%)
were more frequently reported, whereas the age groups "41-65" (39.07%) and "over
65" (27.9%) were the most affected. CONCLUSIONS: Calabria has had a positive
increase in the number of ADRs reported, although it has not yet reached the gold
standard set by World Health Organization (about 600 reports), the data have
shown that PV culture is making inroads in this region and that PV projects
stimulating and increasing PV knowledge are needed.
PMID- 24347985
TI - Annual report on adverse events related with vaccines use in Calabria (Italy):
2012.
AB - Vaccines are administered to large population of healthy individuals,
particularly to millions of infants every year, through national immunization
programs. Although vaccines represent a good defense against some infectious
diseases, their administration may be related with the development of adverse
vaccine events (AVEs); therefore their use is continually monitored to detect
these side effects. In the presents work, we reported the suspected AVEs recorded
in 2012 in Calabria, Italy. We performed a retrospective study on report forms of
patients that developed AVEs in Calabria from January 1, 2012 to December 31,
2012. Naranjo score was used to evaluate the association between AVEs and
vaccines and only suspected AVEs definable as certain, probable, or possible were
included in this analysis. During the study period, we evaluated 461 records of
adverse drug reactions (ADRs) and 18 (3.9%) were probably induced by vaccination.
AVEs were common in females (almost 77.7%) and in children aged 0-3 years. The
largest number of non-serious AVEs involved "skin and subcutaneous tissue
disorders" and "general disorders and administration site conditions." In
conclusion, we documented that in Calabria the total number of AVEs is very low
and it may be useful to increase the pharmacovigilance culture in order to
evaluate the safety of these products in large populations.
PMID- 24347986
TI - Limitations and obstacles of the spontaneous adverse drugs reactions reporting:
Two "challenging" case reports.
AB - INTRODUCTION: Nowadays, based on several epidemiological data, iatrogenic disease
is an emerging public health problem, especially in industrialized countries.
Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically,
socially, and economically worthy of attention. Spontaneous reporting system for
suspected ADRs represents the cornerstone of the pharmacovigilance, because it
allows rapid detection of potential alarm signals related to drugs use. However,
spontaneous reporting system shows several limitations, which are mainly related
to under-reporting. In this paper, we describe two particular case reports, which
emphasize some reasons of under-reporting and other common criticisms of
spontaneous reporting systems. MATERIALS AND METHODS: We performed a computer
aided search of Medline, PubMed, Embase, Cochrane library databases, national and
international databases of suspected ADRs reports in order to identify previous
published case reports and spontaneous reports about the ADRs reviewed in this
paper, and to examine the role of suspected drugs in the pathogenesis of the
described adverse reactions. RESULTS: First, we reported a case of tizanidine
induced hemorrhagic cystitis. In the second case report, we presented an episode
of asthma exacerbation after taking bimatoprost. Through the review of these two
cases, we highlighted some common criticisms of spontaneous reporting systems:
under-reporting and false causality attribution. DISCUSSION AND CONCLUSION:
Healthcare workers sometimes do not report ADRs because it is challenging to
establish with certainty the causal relationship between drug and adverse
reaction; however, according to a key principle of pharmacovigilance, it is
always better to report even a suspicion to generate an alarm in the interest of
protecting public health.
PMID- 24347987
TI - Pharmacovigilance in Asia.
AB - An increase in drug safety concerns in recent years with some high profile drug
withdrawals have led to raising the bar by various stakeholders more importantly
by the regulatory authorities. The number of Adverse Drug Reactions (ADRs)
reported have also resulted in an increase in the volume of data handled and to
understand pharmacovigilance a high level of expertise is required to rapidly
detect drug risks as well as to defend the product against an inappropriate
removal. Proactive pharmacovigilance throughout the product life cycle is the way
forward and the future direction for drug safety in Asia. It has been a constant
challenge to standardize pharmacovigilance in Asia, in the context of clinical
trials and post-marketing pharmacovigilance due to varied geaographical, cultural
and medical practices in these regioon. While major advancements of the
discipline of pharmacovigilance have taken place in the West, not much has been
achieved in Asian countries, though several attempts have been taken. However,
with more clinical trials and clinical research activity being conducted in the
Asian continent, there is an immense need to understand and implement
pharmacovigilance. For this to happen, the mind set of people working in
regulatory agencies, the Pharmaceutical companies, prescribers and
patients/consumers need to change.
PMID- 24347988
TI - Clinical and economic burden of adverse drug reactions.
AB - Adverse drug reactions (ADRs) are unwanted drug effects that have considerable
economic as well as clinical costs as they often lead to hospital admission,
prolongation of hospital stay and emergency department visits. Randomized
controlled trials (RCTs) are the main premarketing methods used to detect and
quantify ADRs but these have several limitations, such as limited study sample
size and limited heterogeneity due to the exclusion of the frailest patients. In
addition, ADRs due to inappropriate medication use occur often in the real world
of clinical practice but not in RCTs. Postmarketing drug safety monitoring
through pharmacovigilance activities, including mining of spontaneous reporting
and carrying out observational prospective cohort or retrospective database
studies, allow longer follow-up periods of patients with a much wider range of
characteristics, providing valuable means for ADR detection, quantification and
where possible reduction, reducing healthcare costs in the process. Overall,
pharmacovigilance is aimed at identifying drug safety signals as early as
possible, thus minimizing potential clinical and economic consequences of ADRs.
The goal of this review is to explore the epidemiology and the costs of ADRs in
routine care.
PMID- 24347989
TI - Management of dermatologic toxicities associated with monoclonal antibody
epidermal growth factor receptor inhibitors: A case review.
AB - INTRODUCTION: The epidermal growth factor receptor inhibitors (EGFRIs), cetuximab
and panitumumab, represent an effective treatment option for patients affected by
metastatic colorectal cancer (mCRC); furthermore, they are relatively devoid of
systemic toxicities, which are commonly observed with standard cytotoxic
chemotherapy. However, the majority of patients treated with these monoclonal
antibodies (mAbs), will experience dermatologic toxicities, most notably the
papulopustular skin rash, which can impact quality-of-life and affect adherence
to therapy. This paper reviews the most recent practices in the management of
skin rash related to anti-epidermal growth factor receptor (EGFR) mAbs, cetuximab
and panitumumab, in the treatment of mCRC. MATERIALS AND METHODS: We reviewed
relevant literature regarding dermatologic toxicities associated with anti-EGFR
mAbs in order to give important indications about prevention and reactive
treatment of skin rash. RESULTS: Two case reports were presented to show how skin
rash could hamper mAb EGFRIs use in clinical practice, underscoring the need of
implementing a comprehensive management strategy of skin toxicity in order to
promote patients' compliance with anti-EGFR therapy and maintain quality-of-life.
Based on randomized data, recent guidelines established by the Multinational
Association for Supportive Care in Cancer Skin Toxicity Study Group suggest that
prophylactic use of oral doxycycline or minocycline reduces the risk and severity
of skin rash, improving clinical outcomes. CONCLUSIONS: At the start of treatment
with cetuximab and panitumumab, the proper patient education about the skin rash
associated with these mAbs and the implementation of a pre-emptive, comprehensive
skin toxicity program significantly contribute to improve adherence to therapy,
optimize anti-EGFR therapy and maintain quality-of-life.
PMID- 24347990
TI - Nexavar((r))-related adverse reactions: Calabrian (Italy) experience for
sorafenib exposition in 2012.
AB - Hepatocellular carcinoma (HCC) remains a major global health problem and Calabria
in the south of Italy is not an exception. Sorafenib is the first and only Food
and Drug Administration approved drug for the treatment of advanced HCC and it is
currently under intensive monitoring by the Health Authorities in Italy Agenzia
Italiana del Farmaco. This general report has been developed with the aim of
briefly reviewing the data found in the reports of adverse reactions (ADRs)
collected in Calabria in 2012 for sorafenib treated patients. Extrapolated data
have highlighted some differences between the adverse drug reactions reported in
patients younger or older than 70 years and other important differences with the
current approved leaflet. Several limitations might be present in data analysis
form spontaneous reporting, however, the relevance of reporting ADRs (dermatitis,
asthenia, vomiting, etc.) for the early identification of drug related signals
has to be underlined.
PMID- 24347991
TI - A possible case of natalizumab-dependent suicide attempt: A brief review about
drugs and suicide.
AB - beta-Interferon therapy is known to be a potential trigger of suicidal behavior,
but this effect has not been previously reported for other multiple sclerosis
(MS) treatments, such as, natalizumab. Here we report the case history of a 32
year-old woman affected by relapsing-remitting MS, who attempted suicide during
natalizumab treatment. This case suggests that a suicidal ideation might be a
rare side effect of natalizumab. Nevertheless, this case represents the first
evidence of the new adverse drug reaction related to natalizumab treatment. We
should alert clinicians to be aware of the possibility of paradoxical activation
of suicidality during its therapeutic use. The main purpose of the present
article is to use this case to review the possible relationship between suicidal
behavior and drugs.
PMID- 24347992
TI - Corticosteroid-related central nervous system side effects.
AB - Corticosteroids have been used since the 50s as anti-inflammatory and
immunosuppressive drugs for the treatment of several pathologies such as asthma,
allergy, rheumatoid arthritis, and dermatological disorders. Corticosteroids have
three principal mechanisms of action: 1) inhibit the synthesis of inflammatory
proteins blocking NF-kB, 2) induce the expression of anti-inflammatory proteins
by IkB and MAPK phosphatase I, and 3) inhibit 5-lipoxygenase and cyclooxygenase
2. The efficacy of glucocorticoids in alleviating inflammatory disorders results
from the pleiotropic effects of the glucocorticoid receptors on multiple
signaling pathways. However, they have adverse effects: Growth retardation in
children, immunosuppression, hypertension, hyperglycemia, inhibition of wound
repair, osteoporosis, metabolic disturbances, glaucoma, and cataracts. Less is
known about psychiatric or side effects on central nervous system, as catatonia,
decreased concentration, agitation, insomnia, and abnormal behaviors, which are
also often underestimated in clinical practice. The aim of this review is to
highlight the correlation between the administration of corticosteroids and CNS
adverse effects, giving a useful guide for prescribers including a more careful
assessment of risk factors and encourage the use of safer doses of this class of
drugs.
PMID- 24347993
TI - The safety of ketoprofen in different ages.
AB - Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID), which acts by
blocking cyclooxygenase (COX 1 and 2), an enzyme involved in the production of
prostaglandins, messengers in the development of inflammation. All NSAIDs reduce
signs of inflammation by blocking this enzyme and therefore prostaglandin
production. In Calabria, 3.69% of adverse drug reactions (ADRs) reported in the
National Network of Pharmacovigilance concerns the use of ketoprofen; only in one
case in which the patient was under the age of 12 years, hospitalization was
required for severe episode of pancreatitis. In Italy, Ketoprofen is the 6(th)
drug for ADRs incidence (560 ADRs in the year 2012, of which, 31% are severe).
Despite the high rate of spontaneous reporting, it must be considered that
ketoprofen is one of the most used NSAIDs; therefore, as it happens for other
commonly used drugs (eg, amoxicillin), the total number of ADRs should be related
to the therapeutic use. However, it remains the problem of fragile patients (eg,
children) and the safety of the drug in different ages. This paper presents a
retrospective study on 2012 ADRs reviewing literature on the safety of ketoprofen
in the elderly, children, and during pregnancy.
PMID- 24347994
TI - Multivariate spatial nonparametric modelling via kernel processes mixing.
AB - In this paper we develop a nonparametric multivariate spatial model that avoids
specifying a Gaussian distribution for spatial random effects. Our nonparametric
model extends the stick-breaking (SB) prior of Sethuraman (1994), which is
frequently used in Bayesian modelling to capture uncertainty in the parametric
form of an outcome. The stick-breaking prior is extended here to the spatial
setting by assigning each location a different, unknown distribution, and
smoothing the distributions in space with a series of space-dependent kernel
functions that have a space-varying bandwidth parameter. This results in a
flexible non-stationary spatial model, as different kernel functions lead to
different relationships between the distributions at nearby locations. This
approach is the first to allow both the probabilities and the point mass values
of the SB prior to depend on space. Thus, there is no need for replications and
we obtain a continuous process in the limit. We extend the model to the
multivariate setting by having for each process a different kernel function, but
sharing the location of the kernel knots across the different processes. The
resulting covariance for the multivariate process is in general nonstationary and
nonseparable. The modelling framework proposed here is also computationally
efficient because it avoids inverting large matrices and calculating
determinants, which often hinders the spatial analysis of large data sets. We
study the theoretical properties of the proposed multivariate spatial process.
The methods are illustrated using simulated examples and an air pollution
application to model components of fine particulate matter.
PMID- 24347995
TI - Correlates of individual, and age-related, differences in short-term learning.
AB - Latent growth models were applied to data on multitrial verbal and spatial
learning tasks from two independent studies. Although significant individual
differences in both initial level of performance and subsequent learning were
found in both tasks, age differences were found only in mean initial level, and
not in mean learning. In neither task was fluid or crystallized intelligence
associated with learning. Although there were moderate correlations among the
level parameters across the verbal and spatial tasks, the learning parameters
were not significantly correlated with one another across task modalities. These
results are inconsistent with the existence of a general (e.g., material
independent) learning ability.
PMID- 24347996
TI - Associations between household responsibilities and academic competencies in the
context of education accessibility in Zambia.
AB - The relationship between education and socioeconomic status has been demonstrated
in studies of the developed and the developing world, yet there are communities
in which schooling is either not available to all children or not a preferred
activity for all children. In this study, we investigated the differences between
children in-school and out-of-school in rural and peri-urban communities of
Zambia. As expected, we found that the children in-school performed higher in
domains of adaptive behavior and on assessments of academic achievement (i.e.,
mathematics, reading). Somewhat unexpectedly, however, when controlling for
socioeconomic status, home responsibilities (i.e., chores, work) were a positive
predictor for the performance of the children out-of-school, but a negative
predictor for the children in-school. The relationship between home
responsibilities and academic performance may be bidirectional and differential;
for example, our findings allow for the hypothesis that for in-school children
chores take time away from the studies, but for out-of-school children they
provide some limited mathematics exposure.
PMID- 24347998
TI - Effects of age and experience on contest behavior in the burying beetle,
Nicrophorus vespilloides.
AB - Contest behavior forms an important part of reproductive investment. Life-history
theory predicts that as individuals age and their residual reproductive value
decreases, they should increase investment in contest behavior. However, other
factors such as social experience may also be important in determining age
related variation in contest behavior. To understand how selection acts on
contest behavior over an individual's lifetime, it is therefore important to
tease apart the effects of age per se from other factors that may vary with age.
Here, we independently manipulate male age and social experience to examine their
effects on male contest behavior in the burying beetle Nicrophorus vespilloides.
We found that social experience, but not age, influenced male contest behavior
but that these changes in behavior did not alter contest outcomes. Male size
(relative to his opponent) was overwhelmingly the most important factor
determining contest outcome. Our results suggest that in systems with high
variation in fighting ability among males, there may be little opportunity for
selection to act on factors that influence contest outcomes by altering
motivation to win.
PMID- 24347997
TI - Biparental incubation patterns in a high-Arctic breeding shorebird: how do pairs
divide their duties?
AB - In biparental species, parents may be in conflict over how much they invest into
their offspring. To understand this conflict, parental care needs to be
accurately measured, something rarely done. Here, we quantitatively describe the
outcome of parental conflict in terms of quality, amount, and timing of
incubation throughout the 21-day incubation period in a population of
semipalmated sandpipers (Calidris pusilla) breeding under continuous daylight in
the high Arctic. Incubation quality, measured by egg temperature and incubation
constancy, showed no marked difference between the sexes. The amount of
incubation, measured as length of incubation bouts, was on average 51min longer
per bout for females (11.5h) than for males (10.7h), at first glance suggesting
that females invested more than males. However, this difference may have been
offset by sex differences in the timing of incubation; females were more often
off nest during the warmer period of the day, when foraging conditions were
presumably better. Overall, the daily timing of incubation shifted over the
incubation period (e.g., for female incubation from evening-night to night
morning) and over the season, but varied considerably among pairs. At one
extreme, pairs shared the amount of incubation equally, but one parent always
incubated during the colder part of the day; at the other extreme, pairs shifted
the start of incubation bouts between days so that each parent experienced
similar conditions across the incubation period. Our results highlight how the
simultaneous consideration of different aspects of care across time allows sex
specific investment to be more accurately quantified.
PMID- 24347999
TI - Construct Validation of the Self-Efficacy Teaching and Knowledge Instrument for
Science Teachers-Revised (SETAKIST-R): Lessons Learned.
AB - Described herein is the academic lineage and independent validation of the Self
Efficacy Teaching and Knowledge Instrument for Science Teachers-Revised (SETAKIST
R). Data from 334 K-12 science teachers were analyzed using Partial Credit Rasch
models. Principal components analysis on the person-item residuals suggest two
latent dimensions: Knowledge and Teaching Self-Efficacies. Item-fit statistics
were used to select items for each subscale. Person and item separation
(reliability) indices were quite low, and we noted disordered response patterns
on the person-item maps that revealed problems with item content and/or scaling
for both subscales. These issues include the presence of: verbal negatives,
ambiguous modifiers, counter-intuitive scaling, and an "undecided/uncertain"
option. The SETAKIST-R, in its current form, cannot be recommended as a measure
of science teacher self-efficacy.
PMID- 24348000
TI - Promoting the Positive Development of Boys in High-Poverty Neighborhoods:
Evidence From Four Anti-Poverty Experiments.
AB - This study uses geocoded address data and information about parent's economic
behavior and children's development from four random-assignment welfare and anti
poverty experiments conducted during the 1990s. We find that the impacts of these
welfare and anti-poverty programs on boys' and girls' developmental outcomes
during the transition to early adolescence differ as a function of neighborhood
poverty levels. The strongest positive impacts of these programs are among boys
who lived in high-poverty neighborhoods at the time their parents enrolled in the
studies, with smaller or non-statistically significant effects for boys in lower
poverty neighborhoods and for girls across all neighborhoods. This research
informs our understanding of how neighborhood context and child gender may
interact with employment-based policies to affect children's well-being.
PMID- 24348001
TI - Associations of Mothers' Friendship Quality with Adolescents' Friendship Quality
and Emotional Adjustment.
AB - Little research has examined the association of parents' friendships with
adolescent's well-being, perhaps because the association was considered too
distal. However, developmental theories suggest that contexts in which parents,
but not their children, are situated may be related to child development
(Bronfenbrenner, 1979; 1986). The current work examined associations between the
quality of mothers' own friendships and their adolescent children's friendship
quality and emotional adjustment. Fifth-, eighth-, and eleventh-graders (N = 172)
whose mothers' friendships were characterized by conflict and antagonism reported
having friendships that were high in negative friendship qualities as well as
elevated internalizing symptoms. These associations held after controlling for
mother-child relationship quality, suggesting that mothers' friendships may have
a unique association with adolescents' adjustment.
PMID- 24348002
TI - Do Market Incentives Crowd Out Charitable Giving?
AB - Donations and volunteerism can be conceived as market transactions with a zero
explicit price. However, evidence suggests people may not view zero as just
another price when it comes to pro-social behavior. Thus, while markets might be
expected to increase the supply of assets available to those in need, some worry
such financial incentives will crowd out altruistic giving. This paper reports
laboratory experiments directly investigating the degree to which market
incentives crowd out large, discrete charitable donations in a setting related to
deceased organ donation. The results suggest markets increase the supply of
assets available to those in need. However, as some critics fear, market
incentives disproportionately influence the relatively poor.
PMID- 24348003
TI - Effect of Visuo-Motor Co-location on 3D Fitts' Task Performance in Physical and
Virtual Environments.
AB - : Given the ease that humans have with using a keyboard and mouse in typical, non
colocated computer interaction, many studies have investigated the value of co
locating the visual field and motor workspaces using immersive display
modalities. Significant understanding has been gained by previous work comparing
physical tasks against virtual tasks, visuo-motor co-location versus non
colocation, and even visuo-motor rotational misalignments in virtual environments
(VEs). However, few studies have explored all of these paradigms in context with
each other and it is difficult to perform inter-study comparisons because of the
variation in tested motor tasks. Therefore, using a stereoscopic fish tank
display setup, the goal for the current study was to characterize human
performance of a 3D Fitts' point-to-point reaching task using a stylus-based
haptic interface in the physical, co-located/non-colocated, and rotated VE
visualization conditions.Five performance measures - throughput, initial movement
error, corrective movements, and peak velocity - were measured and used to
evaluate task performance. These measures were studied in 22 subjects (11 male,
11 female, ages 20-32) performing a 3D variant of Fitts' serial task under 10
task conditions: physical, co-located VE, non-colocated VE, and rotated VEs from
45-315 degrees in 45 degrees increments. HYPOTHESES: All performance measures
in the co-located VE were expected to reflect significantly reduced task
performance over the real condition, but also reflect increased performance over
the non-colocated VE condition. For rotational misalignments, all performance
measures were expected to reflect highest performance at 0 degrees , reduce to
lowest performance at 90 degrees and rise again to a local maximum at 180
degrees (symmetric about 0 degrees ). RESULTS: All performance measures showed
that the co-located VE condition resulted in significantly lower task performance
than the physical condition and higher mean performance than the non-colocated VE
condition, but the difference was not statistically significant. Also, rotation
misalignments showed that task performance were mostly reduced to minimums at 90
degrees , 135 degrees , and 225 degrees . We conclude that co-located VEs may not
significantly improve point-to-point reaching performance over non-colocated VEs.
Also, visual rotations of +/-45 degrees affected throughput, efficiency, peak
velocity, and initial movement error, but the number of corrective movements were
not affected until +/-90 degrees .
PMID- 24348004
TI - An Improved Formulation of Hybrid Model Predictive Control With Application to
Production-Inventory Systems.
AB - We consider an improved model predictive control (MPC) formulation for linear
hybrid systems described by mixed logical dynamical (MLD) models. The algorithm
relies on a multiple-degree-of-freedom parametrization that enables the user to
adjust the speed of setpoint tracking, measured disturbance rejection and
unmeasured disturbance rejection independently in the closed-loop system.
Consequently, controller tuning is more flexible and intuitive than relying on
objective function weights (such as move suppression) traditionally used in MPC
schemes. The controller formulation is motivated by the needs of non-traditional
control applications that are suitably described by hybrid production-inventory
systems. Two applications are considered in this paper: adaptive, time-varying
interventions in behavioral health, and inventory management in supply chains
under conditions of limited capacity. In the adaptive intervention application, a
hypothetical intervention inspired by the Fast Track program, a real-life
preventive intervention for reducing conduct disorder in at-risk children, is
examined. In the inventory management application, the ability of the algorithm
to judiciously alter production capacity under conditions of varying demand is
presented. These case studies demonstrate that MPC for hybrid systems can be
tuned for desired performance under demanding conditions involving noise and
uncertainty.
PMID- 24348005
TI - Robust and Efficient Regularized Boosting Using Total Bregman Divergence.
AB - Boosting is a well known machine learning technique used to improve the
performance of weak learners and has been successfully applied to computer
vision, medical image analysis, computational biology and other fields. A
critical step in boosting algorithms involves update of the data sample
distribution, however, most existing boosting algorithms use updating mechanisms
that lead to overfitting and instabilities during evolution of the distribution
which in turn results in classification inaccuracies. Regularized boosting has
been proposed in literature as a means to overcome these difficulties. In this
paper, we propose a novel total Bregman divergence (tBD) regularized LPBoost,
termed tBRLPBoost. tBD is a recently proposed divergence in literature, which is
statistically robust and we prove that tBRLPBoost requires a constant number of
iterations to learn a strong classifier and hence is computationally more
efficient compared to other regularized Boosting algorithms. Also, unlike other
boosting methods that are only effective on a handful of datasets, tBRLPBoost
works well on a variety of datasets. We present results of testing our algorithm
on many public domain databases and comparisons to several other state-of-the-art
methods. Numerical results show that the proposed algorithm has much improved
performance in efficiency and accuracy over other methods.
PMID- 24348006
TI - Beliefs and expectancies in legal decision making: an introduction to the Special
Issue.
AB - This introduction describes what the co-editors believe readers can expect in
this Special Issue. After beliefs and expectancies are defined, examples of how
these constructs influence human thought, feeling, and behavior in legal settings
are considered. Brief synopses are provided for the Special Issue papers on
beliefs and expectancies regarding alibis, children's testimony behavior,
eyewitness testimony, confessions, sexual assault victims, judges' decisions in
child protection cases, and attorneys' beliefs about jurors' perceptions of
juvenile offender culpability. Areas for future research are identified, and
readers are encouraged to discover new ways that beliefs and expectancies operate
in the legal system.
PMID- 24348008
TI - Prejudice-Related Events and Traumatic Stress Among Heterosexuals and Lesbians,
Gay Men and Bisexuals.
AB - This mixed-methods study examined associations between prejudice events and
posttraumatic stress disorder (PTSD) among 382 lesbians, gays, and bisexuals
(LGB) and 126 heterosexuals. Using the Composite International Diagnostic
Interview, we assessed PTSD but relaxed Criterion A1, that is, allowed prejudice
events that did not involve threat to life or physical integrity to also qualify
as traumatic. First, we tested whether exposure to prejudice events differed with
respect to sexual orientation and race. White LGBs were more likely than White
heterosexuals to encounter a prejudice event, but Black and Latino LGBs were no
more likely than White LGBs to experience a prejudice event. Second, we used
qualitative analysis to examine the prejudice events that precipitated relaxed
Criterion A1 PTSD among 8 participants. Two specific themes emerged: the need to
make major changes and compromised sense of safety and security following
exposure to the prejudice event.
PMID- 24348009
TI - A comprehensive phylogenetic analysis of deadenylases.
AB - Deadenylases catalyze the shortening of the poly(A) tail at the messenger
ribonucleic acid (mRNA) 3'-end in eukaryotes. Therefore, these enzymes influence
mRNA decay, and constitute a major emerging group of promising anti-cancer
pharmacological targets. Herein, we conducted full phylogenetic analyses of the
deadenylase homologs in all available genomes in an effort to investigate
evolutionary relationships between the deadenylase families and to identify
invariant residues, which probably play key roles in the function of
deadenylation across species. Our study includes both major Asp-Glu-Asp-Asp
(DEDD) and exonuclease-endonuclease-phospatase (EEP) deadenylase superfamilies.
The phylogenetic analysis has provided us with important information regarding
conserved and invariant deadenylase amino acids across species. Knowledge of the
phylogenetic properties and evolution of the domain of deadenylases provides the
foundation for the targeted drug design in the pharmaceutical industry and modern
exonuclease anti-cancer scientific research.
PMID- 24348007
TI - Genetic screen of African Americans with Fuchs endothelial corneal dystrophy.
AB - PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a genetically
heterogeneous disorder that has been primarily studied in patients of European or
Asian ancestry. Given the sparse literature on African Americans with FECD, we
sought to characterize the genetic variation in three known FECD candidate genes
in African American patients with FECD. METHODS: Over an 8-year period, we
enrolled 47 African American probands with FECD. All participants were clinically
examined with slit-lamp biomicroscopy, and when corneal tissue specimens were
available, histopathologic confirmation of the clinical diagnosis was obtained.
The coding regions of known FECD susceptibility genes collagen, type VIII, alpha
2 (COL8A2); solute carrier family 4, sodium borate transporter, member 11
(SLC4A11); and zinc finger E-box binding homeobox 1 (ZEB1 [also known as TCF8])
were Sanger sequenced in the 47 probands using DNA isolated from blood samples.
RESULTS: Twenty-two coding variants were detected across the COL8A2, SLC4A11, and
ZEB1 genes; six were nonsynonymous variants. Three novel coding variants were
detected: a synonymous variant each in COL8A2 and SLC4A11 and one nonsynonymous
variant in ZEB1 (p.P559S), which is predicted to be benign and tolerated, thus
making its physiologic consequence uncertain. CONCLUSIONS: Variation in the
COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of our
African American cases and as such does not appear to significantly contribute to
the genetic risk of FECD in African Americans. This observation is on par with
findings from previous sequencing studies involving European or Asian ancestry
patients with FECD.
PMID- 24348010
TI - Vitrectomy in double-perforation gunshot injury.
AB - OBJECTIVE: This study sought to evaluate the result of pars plana vitrectomy in
patients with gunshot wounds involving double perforation. METHODS: This was a
retrospective, noncomparative, interventional case series. RESULTS: Eighteen
patients (18 eyes) with double-perforation gunshot injuries were treated from
February 2010 to March 2012. The group included 16 men (88%) and two women (11%);
the mean age was 24 (15-33) years. In each case, vitrectomy was scheduled 1-6
weeks after repair of the entrance site. Associated retinal detachments were
observed in two eyes (11%), retinal incarceration was observed surrounding the
exit site in three eyes (16%), and retention of an intraocular foreign body was
observed in two cases. After a follow-up period of 8 +/- 2 months, two eyes (11%)
had achieved visual acuity (VA) of 0.5, nine eyes (50%) had achieved VA between
0.5 and 0.1, and seven eyes (38%) had achieved VA between 0.1 and hand movement.
The main reasons for functional failure (VA 0.1 to hand movement) were macular
dragging (due to fibrosis at the exit site near the macula) in seven cases (38%),
submacular hemorrhage in four cases (22%), and epimacular fibrosis in five cases
(27%). All cases developed postoperative exotropia. One case (5%) developed
postoperative hemorrhage. No cases exhibited signs of postoperative redetachment.
CONCLUSION: The outcome of pars plana vitrectomy in cases with double
perforations is variable. Factors including the surgeon's skill level, the time
to surgery, and the efficacy of the intraocular tamponade affect the
postoperative outcome.
PMID- 24348012
TI - Diabetic papillopathy with macular edema treated with intravitreal ranibizumab.
AB - We report a case of diabetic papillopathy that demonstrated a resolution of optic
disk swelling and rapid visual recovery when intravitreal ranibizumab was
administered. A 51-year-old male presented with acute painless visual loss in his
right eye. His vision was 20/320 in the right eye and 20/50 in the left eye.
Fundus examination of the right eye showed nonproliferative diabetic retinopathy
with macular edema and a swollen optic disk. Fluorescein angiography showed dye
leakage from the right optic disk. Optical coherent tomography revealed a
significant increase in retinal nerve fiber-layer thickness. Magnetic resonance
imaging of the brain was normal. The patient received a single intravitreal
ranibizumab (0.5 mg) injection. Two weeks following injection, there was marked
regression of the disk swelling and improvement of macular edema, with vision
improving to 20/100. Three months following injection, there was complete
resolution of the optic disk swelling. No further treatment was required.
PMID- 24348011
TI - Comparison of high-resolution Scheimpflug and high-frequency ultrasound
biomicroscopy to anterior-segment OCT corneal thickness measurements.
AB - BACKGROUND: The purpose of this study was to compare and correlate central
corneal thickness in healthy, nonoperated eyes with three advanced anterior
segment imaging systems: a high-resolution Scheimpflug tomography camera
(Oculyzer II), a spectral-domain anterior-segment optical coherence tomography
(AS-OCT) system, and a high-frequency ultrasound biomicroscopy (HF-UBM) system.
METHODS: Fifty eyes randomly selected from 50 patients were included in the
study. Inclusion criteria were healthy, nonoperated eyes examined consecutively
by the same examiner. Corneal imaging was performed by three different methods,
ie, Oculyzer II, spectral-domain AS-OCT, and FH-UBM. Central corneal thickness
measurements were compared using scatter diagrams, Bland-Altman plots (with bias
and 95% confidence intervals), and two-paired analysis. RESULTS: The coefficient
of determination (r (2)) between the Oculyzer II and AS-OCT measurements was
0.895. Likewise, the coefficient was 0.893 between the Oculyzer II and HF-UBM and
0.830 between the AS-OCT and HF-UBM. The trend line coefficients of linearity
were 0.925 between the Oculyzer II and the AS-OCT, 1.006 between the Oculyzer II
and HF-UBM, and 0.841 between the AS-OCT and HF-UBM. The differences in average
corneal thickness between the three pairs of CCT measurements were -6.86 MUm
between the Oculyzer II and HF-UBM, -12.20 MUm between the AS-OCT and Oculyzer
II, and +19.06 MUm between the HF-UBM and AS-OCT. CONCLUSION: The three methods
used for corneal thickness measurement are highly correlated. Compared with the
Scheimplug and ultrasound devices, the AS-OCT appears to report a more accurate,
but overally thinner corneal pachymetry.
PMID- 24348013
TI - First case of fungal keratitis caused by Pestalotiopsis clavispora.
AB - PURPOSE: To report the isolation of Pestalotiopsis clavispora from the cornea of
a patient with recurrent keratitis. CASE REPORT: A 73-year-old male gardener
presented with conjunctival injection and an oval infiltrate with feathery
margins in the temporal half of the cornea in the right eye. His ocular history
in the right eye included cataract surgery, five episodes of herpes simplex
keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated
with corticosteroids for years. Light microscopy of corneal scrapings revealed a
filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical
voriconazole and pimaricin ointment was commenced. One month later, the
infiltrate resolved. The antifungal agents were discontinued 7 months later, and
keratitis relapsed 4 days after the discontinuation. The fungus was isolated and
identified by molecular techniques as P. clavispora. Based on the results of
antifungal susceptibility testing, treatment with topical and intravenous
micafungin was initiated. The corneal infiltrate resolved 1 month after the
relapse. CONCLUSION: Molecular identification of the pathogen, and antifungal
susceptibility testing, are useful in treating patients with fungal keratitis
caused by a rare human pathogen.
PMID- 24348014
TI - Simplified local anesthesia technique for external dacryocystorhinostomy without
nasal packing: a new technique and pilot study outcome.
AB - BACKGROUND: The purpose of this paper is to describe a simplified local
anesthesia technique for external dacryocystorhinostomy (EXT-DCR). METHODS: In
this pilot, retrospective, noncomparative, interventional case series, 448
patients (480 eyes) underwent EXT-DCR using a simplified local anesthesia
technique. Nasal mucosal anesthesia was achieved using combined application of 6
mL of oxymetazoline 0.025% nasal spray and lidocaine 1% in the same spray bottle,
without any packing of the nose with either pledgets or ribbon gauze. Local
infiltration anesthesia consisted of subcutaneous injection of a 7 mL mixture of
2% lidocaine with 1:100,000 epinephrine injected on the flat side of the nose
beneath the incision site, in addition to a second medial peribulbar injection (3
mL, 2% lidocaine without epinephrine). RESULTS: Successful unilateral or
bilateral EXT-DCR was achieved in 432/448 patients (96.4%). Four patients could
not tolerate the procedure under local anesthesia and were converted to general
anesthesia. Four patients required additional local anesthetic injections because
of intolerable pain. Heavy sedation was essential in eight uncooperative patients
because surgical manipulation was impossible. The remaining patients tolerated
the procedure well. The intraoperative bleeding rate was very low except in one
patient. Mean operative time was 16 minutes. Severe postoperative epistaxis was
observed in four patients. Temporary anosmia developed in one patient.
CONCLUSION: Our simplified local anesthesia approach of EXT-DCR is convenient for
the patient because it avoids unnecessary nasal packing. It is also safe and
effective, as evidenced by the high rate of successful completion of the
procedure without conversion to general anesthesia or the need for supplemental
local anesthesia.
PMID- 24348015
TI - Glistenings in hydrophobic acrylic intraocular lenses do affect visual function.
PMID- 24348016
TI - Ocular cysticercosis in a 32-year-old man in Abuja: ultrasonic features as an aid
in diagnosis.
AB - We report the case of a 32-year-old man suffering from intraocular cysticercosis,
with special emphasis on the use of B-scan ultrasound in the diagnosis and
management of the condition. An 8000 B-Scan Scanmate was used to obtain the
ultrasound images. The patient had worked on a pig farm a few years before
presentation. He presented with shadows seen in the right eye. Binocular indirect
ophthalmoscopy revealed that he had a choroidal detachment in the right eye
inferotemporally. B-scan ultrasound revealed a subretinal subchoroidal cyst with
a thick wall containing well defined intracystic echogenic entities representing
scolices, and an associated retinal detachment. These findings appear to be
pathognomonic. Excision of the cyst through a trans-scleral approach revealed a
yellowish serous fluid, with scolices of cysticercus later confirmed
histologically. B-scan ultrasound is extremely useful in the diagnosis of ocular
cysticercosis and the findings can be pathognomonic.
PMID- 24348017
TI - Lessons learned from peginesatide in the treatment of anemia associated with
chronic kidney disease in patients on dialysis.
AB - Peginesatide is the newest erythropoietin-stimulating agent (ESA) in the quest
for the ideal treatment of anemia in chronic kidney disease (CKD) patients.
Reduced frequency of administration along with a possibly lower cost as a result
of simpler manufacturing techniques compared with other available agents makes
peginesatide a highly desirable product in the competitive ESA market.
Peginesatide is noninferior to the other ESAs, and has a good safety profile in
patients on hemodialysis. The higher rates of adverse cardiovascular events
reported in CKD patients not on dialysis in the recent Phase III studies require
further, better planned, studies. Peginesatide had to be withdrawn from the
market in the US after some reports of hypersensitivity reactions to the drug.
This is a setback, but the scientific advances gained as a result of this product
development can be used to develop other, newer products.
PMID- 24348018
TI - Conversion to generic cyclosporine A in stable chronic patients after heart
transplantation.
AB - BACKGROUND: Cyclosporine A (CSA) is a narrow therapeutic index drug. Available
CSA products differ in the constitution of their emulsion. To compare intra
individual differences after a conversion to a generic CSA, a retrospective
single-center study was initiated. METHODS: Twenty adult stable chronic (>24
months post heart transplant) recipients were included in the present
retrospective study. These patients were previously switched from Sandimmune
Neoral(r) to the generic CSA (Equoral(r)) according to the patients' preference
during the clinical routine. Dose-normalized trough levels (DNL) and trough
levels (C0) at 8 months, 4 months, and 2 weeks before the switch were
retrospectively compared with the corresponding values at 2 weeks, 4 months, and
8 months after the switch to the generic CSA. Additionally, changes in the
routine laboratory parameters, the number of treated rejection episodes, and the
adherence to the CSA target levels were compared. RESULTS: The mean DNL (adapted
to the daily CSA dose in mg) was 0.71+/-0.26 (ng/mL)/mg on Neoral therapy; on
Equoral it was 0.68+/-0.23 (ng/mL)/mg, (P=0.38). In comparison to the CSA daily
dose prior to the conversion, at postconversion, no significant changes of CSA
daily dose were observed (Neoral 140.67+/-39.81 mg versus Equoral 134.58+/-41.61
mg; P=0.13). No rejection episodes requiring therapy occurred prior to or
postconversion (P=0.99). Additionally, no statistically significant changes of
routine laboratory parameters regarding the Modification of Diet in Renal Disease
or hematological parameters were seen (all P=not significant). No adverse events
after the conversion were observed. CONCLUSION: This study in chronic and stable
HTx patients demonstrated no statistically significant differences in the CSA DNL
after a conversion to generic CSA (Equoral). The generic CSA was generally well
tolerated. We concluded that a conversion from Neoral to Equoral is safe and
clinically feasible in this distinct patient population. However, multiple
switches between different generic immunosuppressants must especially be avoided
in the interest of patient safety, and close follow-up examinations must be
warranted.
PMID- 24348019
TI - Combined letrozole and clomiphene versus letrozole and clomiphene alone in
infertile patients with polycystic ovary syndrome.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine
disorder in women of childbearing age (6.8%-18%), is among the most common causes
of infertility due to ovulation factors, and accounts for 55%-70% of infertility
cases caused by chronic anovulation. In this study, we used a combination of
letrozole and clomiphene in patients resistant to both drugs individually, and
studied the effects of this combination in ovulation and pregnancy in resistant
PCOS patients. METHODS: The study population included infertile couples diagnosed
as PCOS in the wife. The women used clomiphene for at least six cycles in order
to ovulate after failure to form the dominant follicle, and were then put on
letrozole for four cycles. Patients who were unable to form the dominant follicle
were enrolled on letrozole and clomiphene combination therapy. RESULTS: One
hundred enrolled patients underwent 257 cycles of a combination of letrozole and
clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44
were unable to do so (17.1%). The number of mature follicles was 2.3+/-1.1. The
mean endometrial thickness in patients on the day of human chorionic gonadotropin
administration was 8.17+/-1.3 mm. The pregnancy rate was 42%. CONCLUSION:
According to the results of this study, it can be proposed that in PCOS patients
resistant to clomiphene and letrozole used as single agents, a combination of the
two drugs can be administered before using more aggressive treatment that may
have severe complications or surgery. This combination may also be used as a
first-line therapy to induce ovulation in severe cases of PCOS in order to save
time and expense.
PMID- 24348020
TI - Atomoxetine affects transcription/translation of the NMDA receptor and the
norepinephrine transporter in the rat brain--an in vivo study.
AB - Attention-deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed
neurodevelopmental disorder. The norepinephrine transporter (NET) inhibitor
atomoxetine, the first nonstimulant drug licensed for ADHD treatment, also acts
as an N-methyl-D-aspartate receptor (NMDAR) antagonist. The compound's effects on
gene expression and protein levels of NET and NMDAR subunits (1, 2A, and 2B) are
unknown. Therefore, adolescent Sprague Dawley rats were treated with atomoxetine
(3 mg/kg, intraperitoneal injection [i.p.]) or saline (0.9%, i.p.) for 21
consecutive days on postnatal days (PND) 21-41. In humans, atomoxetine's earliest
clinical therapeutic effects emerge after 2-3 weeks. Material from prefrontal
cortex, striatum (STR), mesencephalon (MES), and hippocampus (HC) was analyzed
either directly after treatment (PND 42) or 2 months after termination of
treatment (PND 101) to assess the compound's long-term effects. In rat brains
analyzed immediately after treatment, protein analysis exhibited decreased levels
of the NET in HC, and NMDAR subunit 2B in both STR and HC; the transcript levels
were unaltered. In rat brains probed 2 months after final atomoxetine exposure,
messenger RNA analysis also revealed significantly reduced levels of genes coding
for NMDAR subunits in MES and STR. NMDAR protein levels were reduced in STR and
HC. Furthermore, the levels of two SNARE (soluble N-ethylmaleimide-sensitive
factor attachment protein receptor) proteins, synaptophysin and synaptosomal
associated protein 25, were also significantly altered in both treatment groups.
This in vivo study detected atomoxetine's effects beyond NET inhibition. Taken
together, these data reveal that atomoxetine seems to decrease glutamatergic
transmission in a brain region-specific manner. Long-term data show that the
compound's impact is not due to an acute pharmacological effect but lasts or even
amplifies after a drug-free period of 2 months, leading to altered development of
synaptic composition. These alterations might contribute to atomoxetine's
clinical effects in the treatment of ADHD, a neurodevelopmental disorder in which
synaptic processes and especially a dysregulated glutamatergic metabolism seem to
be involved.
PMID- 24348021
TI - P-glycoprotein alters blood-brain barrier penetration of antiepileptic drugs in
rats with medically intractable epilepsy.
AB - P-glycoprotein is one of the earliest known multidrug transporters and plays an
important role in resistance to chemotherapeutic drugs. In this study, we
detected levels of P-glycoprotein and its mRNA expression in a rat brain model of
medically intractable epilepsy established by amygdala kindling and drug
selection. We investigated whether inhibition of P-glycoprotein affects the
concentration of antiepileptic drugs in cortical extracellular fluid. We found
that levels of P-glycoprotein and its mRNA expression were upregulated in
epileptic cerebral tissue compared with cerebral tissue from normal rats. The
concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very
low in the cortical extracellular fluid of rats with medically intractable
epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These
results show that increased P-glycoprotein levels alter the ability of
carbamazepine and phenytoin to penetrate the blood-brain barrier and reduce the
concentrations of these agents in extracellular cortical fluid. High P
glycoprotein levels may be involved in resistance to antiepileptic drugs in
medically intractable epilepsy.
PMID- 24348022
TI - Development and characterization of gastroretentive sustained-release formulation
by combination of swelling and mucoadhesive approach: a mechanistic study.
AB - BACKGROUND: Acyclovir has pharmacokinetic limitations, including poor oral
bioavailability of 15%-30%, high variability, and short elimination half-life of
2.3 hours. These limitations necessitate frequent administration of acyclovir, up
to five times daily, leading to poor patient compliance, which in turn leads to a
reduction in therapeutic efficacy and development of resistance. METHODS: A
gastroretentive sustained-release (GR) formulation of acyclovir, based on a
combination of swelling and mucoadhesive mechanisms, has been developed.
Composition has been optimized after evaluation of different polymers, carbomer,
polyethylene oxide, and sodium alginate alone and/or in combination. GR
formulations were characterized for in-process quality-control tests, drug
release and release rate kinetics, similarity factor analysis, swelling index,
and matrix erosion. RESULTS: A formulation containing a combination of carbomer
and polyethylene oxide had the highest similarity of drug release compared with a
target drug-release profile obtained by pharmacokinetic simulations. The
measurement of mucoadhesive strength, carried out with a texture analyzer, showed
that the mucoadhesive strength of the GR formulation was significantly higher
than that of the immediate-release (IR) tablet. The optimized GR formulation was
found to be retained in the upper part of the gastrointestinal tract for 480
minutes; the IR tablet was retained for only 90 minutes as measured using a
gastrointestinal retention study in albino rabbits. The GR formulation was also
found to maintain more sustained plasma concentrations than the IR tablet. Mean
residence time of the GR formulation was 7 hours versus 3.3 hours for the IR
formulation. The relative bioavailability of the GR formulation was 261% of the
IR formulation. CONCLUSION: The GR formulation of acyclovir, based on swelling
and mucoadhesive mechanisms, has prolonged retention in the upper
gastrointestinal tract, sustained in vitro drug release, prolonged in vivo
absorption, and better bioavailability than the IR formulation. Such a
formulation would improve patient compliance and increase the efficacy of
therapy.
PMID- 24348023
TI - Review of the rational use and adverse reactions to human serum albumin in the
People's Republic of China.
AB - Human serum albumin (HSA) is an ideal natural colloid that has been widely used
in clinical practice for supplemental albumin or as a plasma substitute during
therapeutic plasma exchanges to redress hypoproteinemia. However, a paucity of
well-designed clinical trials, a lack of a clear cut survival benefit, and
frequent case reports of adverse drug reaction (ADR) make the use of HSA
controversial. This study aims to review and to comment on the reported ADRs of
HSA in the People's Republic of China, so as to provide the basis for rational
HSA use in clinical settings. Data on the ADR case reports from HSA
administration between January 1990 and December 2012 available from the China
National Knowledge Infrastructure (CNKI) database, Wanfang data (WF), and Chinese
Biomedical Literature (CBM) were reviewed. The reasons for using HSA, the types
of ADRs, the causality of ADRs and the rationality for HSA administration were
extracted and analyzed. In total, 61 cases of ADR reports were identified of
which the primary disease of patients using HSA was malignant tumor (34.42%). The
primary ADR was anaphylaxis (59.02%). Of the 61 cases, 30 were caused by
irrational use of HSA. The most common irrational use was off-label use (56.67%),
followed by inappropriate infusion rate. Therefore, we conclude that to avoid the
occurrence of ADRs, guidelines for using HSA are needed to guarantee its rational
use and HSA should be used strictly according to these guidelines. In addition,
medical staff, including clinical pharmacists and nurses, should pay more
attention to the patients who inject HSA to ensure its safe use in the clinic.
PMID- 24348024
TI - Three Dimensional Structure Prediction of Fatty Acid Binding Site on Human
Transmembrane Receptor CD36.
AB - CD36 is an integral membrane protein which is thought to have a hairpin-like
structure with alpha-helices at the C and N terminals projecting through the
membrane as well as a larger extracellular loop. This receptor interacts with a
number of ligands including oxidized low density lipoprotein and long chain fatty
acids (LCFAs). It is also implicated in lipid metabolism and heart diseases. It
is therefore important to determine the 3D structure of the CD36 site involved in
lipid binding. In this study, we predict the 3D structure of the fatty acid (FA)
binding site [127-279 aa] of the CD36 receptor based on homology modeling with X
ray structure of Human Muscle Fatty Acid Binding Protein (PDB code: 1HMT).
Qualitative and quantitative analysis of the resulting model suggests that this
model was reliable and stable, taking in consideration over 97.8% of the residues
in the most favored regions as well as the significant overall quality factor.
Protein analysis, which relied on the secondary structure prediction of the
target sequence and the comparison of 1HMT and CD36 [127-279 aa] secondary
structures, led to the determination of the amino acid sequence consensus. These
results also led to the identification of the functional sites on CD36 and
revealed the presence of residues which may play a major role during ligand
protein interactions.
PMID- 24348025
TI - Evolution of cardiovascular risk factors and ischemic heart disease in an elderly
urban Romanian population over the course of 1 year.
AB - BACKGROUND: Romania has some of the highest mortality figures in the world
attributable to ischemic heart disease and stroke among both men and women.
OBJECTIVES: To assess the changes in cardiovascular risk factors and ischemic
heart disease in a group of subjects over 65 years of age during 1 year in an
urban community of Romania. MATERIALS AND METHODS: We studied 515 subjects (264
women and 251 men) with a mean age of 73.41+/-6.44 years, followed up over the
course of 1 year in order to determine the changes that occurred in
cardiovascular risk factors and in the evolution of ischemic heart disease. At
the beginning and after 1 year, we determined the following parameters:
anthropometric measurements, blood pressure, smoking status, lipid profile (total
cholesterol, triglycerides, high-density lipid cholesterol, low-density lipid
cholesterol), fasting plasma glucose, and the presence of ischemic heart disease.
RESULTS: There were no differences between the first and second assessments
concerning the incidence of smoking (12.3% versus (vs) 12.5%), obesity (25% vs
26%), diabetes mellitus (19% vs 22.9%), or hypertension (88.2% vs 92.2%).
Statistically significant differences were recorded regarding dyslipidemia (40.6%
vs 30.3%, P<0.001). Cholesterol median values decreased (204 mg/dL vs 194 mg/dL,
P=0.003), while median concentrations of plasma glucose increased (101 mg/dL vs
105 mg/dL, P<0.05). At the same time, we noted a higher incidence of ischemic
heart disease (51.65% vs 63%). CONCLUSION: Our data show that in subjects over 65
years of age, cardiovascular disease occurs more often in women, but with certain
features that should be taken into account. In addition, we point out the
importance of reducing cardiovascular risk factors. However, we should not expect
a major decrease or improvement in cardiovascular risk factors with such a short
follow-up. Such results will be achieved only through long-term interventions.
PMID- 24348026
TI - Fall-related admissions after fast-track total hip and knee arthroplasty - cause
of concern or consequence of success?
AB - BACKGROUND: Total hip (THA) and knee arthroplasty (TKA) are common procedures in
elderly persons, who are at potential increased risk of postoperative fall due to
loss of muscle strength and impaired balance. Fast-track surgery with early
mobilization and opioid-sparing analgesia have improved outcomes after these
procedures, but early mobilization and short hospitalization length of stay (LOS)
could potentially increase the risk of falls after discharge. We investigated
injuries, circumstances, and the timing of fall-related hospital admissions 90
days after fasttrack THA and TKA. METHODS: This was a prospective, descriptive
multicenter study on fall-related hospital admissions, in 5145 elective fast
track THA and TKA patients, with complete 90-day follow up through the Danish
National Patient registry and medical charts. RESULTS: Of 83 (1.6%) fall-related
hospital admissions, 43 (51.8%) were treated in the Emergency Room and 40 (48.2%)
were admitted to a regular ward. The median LOS after surgery was 3 days
(interquartile range [IQR]: 2-3) in fallers versus (vs) 2 days (IQR: 2-3)
(P=0.022) in patients without falls. Injuries were classified as "none" or minor
in 39.8%, moderate in 9.6%, and major in 50.6%. Most falls (54.8%) occurred
within 1 month of discharge. Falls due to physical activity (12.0%) and extrinsic
factors (14.5%) occurred later than did surgery-related falls (73.5%),
contributing to 40% of all falls >30 days after discharge. In multivariate
analysis, age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.0-1.08)
(P=0.001), living alone (OR: 2.09; 95% CI: 1.20-3.62) (P=0.009), and psychiatric
disease (OR: 2.80; 95% CI: 1.42-5.50) (P=0.001) were associated with surgery
related falls, whereas the use of a walking aid (OR: 1.20; 95% CI: 0.67-2.16)
(P=0.544) and LOS <=4 days (OR:1.19; 95% CI: 0.52-1.28) (P=0.680) was not.
CONCLUSION: Hospital admissions due to falls are most frequent within the first
month after fast-track THA and TKA. The overall incidence of surgery-related
falls amongst these patients is low, declines after the first month, and is
related to patient characteristics rather than short LOS. The effect of
interventions aimed at surgery-related falls should focus on the first 30 days
after surgery and differentiate between the causes of falling.
PMID- 24348027
TI - Overall and abdominal obesity indicators had different association with central
arterial stiffness and hemodynamics independent of age, sex, blood pressure,
glucose, and lipids in Chinese community-dwelling adults.
AB - OBJECTIVE: Limited large sample studies have specially compared overall and
abdominal obesity in relation to central arterial stiffness and hemodynamics in
community-dwelling adults, especially in the People's Republic of China. This
study aimed to compare the relationship between an overall obesity indicator
(body mass index [BMI]), an abdominal obesity index (waist circumference [WC]),
and central arterial stiffness and hemodynamics, independent of age, sex, blood
pressure, glucose, and lipids, in Chinese community-dwelling adults. METHODS: For
2,624 adults in this study, anthropometric indices, such as BMI and WC, were
measured. Central arterial stiffness was assessed by carotid-femoral pulse wave
velocity (cfPWV). Central hemodynamics was represented by central pulse pressure
(cPP). RESULTS: Both overall and abdominally obese adults were older, with
significantly higher cfPWV, cPP, peripheral pulse pressure (pPP), fasting blood
glucose (FBG), and low-density lipoprotein-cholesterol (LDL-C), and significantly
lower high-density lipoprotein-cholesterol (HDL-C). After adjusting for age and
sex, both the overall and abdominally obese individuals had independently higher
pPP, FBG, and LDL-C levels, and lower HDL-C level. The overall obese individuals
had independently higher cPP, but not cfPWV, after adjusting for age and sex,
while the abdominally obese individuals had independently higher cfPWV, but not
cPP. After adjusting for age, sex, pPP, FBG, LDL-C, and HDL-C, WC, but not BMI,
was independently correlated with cfPWV, and BMI, but not WC, was independently
associated with cPP. Age, sex, pPP, FBG, and HDL-C levels have independent
association with cfPWV. Age, sex, pPP, but not FBG and HDL-C levels, have
independent association with cPP. CONCLUSION: The abdominal obesity index (WC),
rather than the overall obesity indicator (BMI), was related to central arterial
stiffness, independent of age, sex, blood pressure, glucose and lipids, while the
overall obesity indicator (BMI), rather than the abdominal obesity indicator
(WC), was independently correlated with central hemodynamics. Age, sex, and blood
pressure were independently associated with central arterial stiffness and
hemodynamics, but blood glucose and lipids were independently associated with
central arterial stiffness, rather than hemodynamics.
PMID- 24348028
TI - Rates, variability, and associated factors of polypharmacy in nursing home
patients.
AB - OBJECTIVES: To determine the rate and variability of polypharmacy in nursing home
(NH) residents and investigate its relationship to age, sex, functional status,
length of stay, and comorbidities. METHODS: We conducted a cross sectional,
multicenter study that included six nursing homes. Demographic, clinical
characteristics, Charlson comorbidity index (CCI), the number and classes of
chronic medications, rate of polypharmacy >5 drugs (per day) and polypharmacy >7
drugs (per day) were recorded. RESULTS: Nine hundred and ninety-three residents
were included; 750 (75.5%) fully dependent residents and 243 (24.5%) mobile
demented residents requiring institutional care. The mean age was 85.04+/-7.55
(65-108) years. The mean rates of polypharmacy >5 drugs and polypharmacy >7 drugs
were 42.6% and 18.6%, respectively. Differences in polypharmacy >5 drugs and
polypharmacy >7 drugs were observed in NHs 24.7%-56% and 4.9%-30.4%, respectively
(P<0.001). Mean number of chronic drugs per resident was 5.14+/-2.60 from 3.81+/
2.24 to 5.95+/-2.73 (P<0.001). No differences in polypharmacy were found between
sex and fully dependent versus mobile demented residents. The most common
medications taken were for gastrointestinal, neurological, and cardiovascular
disorders. Regression analysis revealed four independent variables for
polypharmacy >5 drugs: groups aged 75-84 and >85 relative to 65-74, odds ratio
(OR) 0.46 (95% confidence interval [CI] 0.27-0.78) P=0.004, OR 0.35 (95%
confidence interval 0.19-0.53), respectively, P<0.001; length of stay >2 years,
OR 0.51 (95% CI 0.36-0.73) P<0.001; CCI, OR 1.58 (95% CI 1.42-1.75) P<0.001; and
feeding tube versus normal feeding, OR 0.27 (95% CI 0.12-0.60) P=0.001.
CONCLUSION: Rates of polypharmacy in NHs are high with significant variability.
Variability rates of polypharmacy, distinct residents' characteristics, and
excessive use of certain drug groups may indicate that a decrease in medication
is potentially feasible.
PMID- 24348029
TI - Effect of 6 months of whole body vibration on lumbar spine bone density in
postmenopausal women: a randomized controlled trial.
AB - BACKGROUND: The issue of osteoporosis-induced fractures has attracted the world's
attention. Postmenopausal women are particularly at risk for this type of
fracture. The nonmedicinal intervention for postmenopausal women is mainly
exercise. Whole body vibration (WBV) is a simple and convenient exercise. There
have been some studies investigating the effect of WBV on osteoporosis; however,
the intervention models and results are different. This study mainly investigated
the effect of high-frequency and high-magnitude WBV on the bone mineral density
(BMD) of the lumbar spine in postmenopausal women. METHODS: This study randomized
28 postmenopausal women into either the WBV group or the control group for a 6
month trial. The WBV group received an intervention of high-frequency (30 Hz) and
high-magnitude (3.2 g) WBV in a natural full-standing posture for 5 minutes,
three times per week, at a sports center. Dual-energy X-ray absorptiometry was
used to measure the lumbar BMD of the two groups before and after the
intervention. RESULTS: Six months later, the BMD of the WBV group had
significantly increased by 2.032% (P=0.047), while that of the control group had
decreased by 0.046% (P=0.188). The comparison between the two groups showed that
the BMD of the WBV group had increased significantly (P=0.016). CONCLUSION: This
study found that 6 months of high-frequency and high-magnitude WBV yielded
significant benefits to the BMD of the lumbar spine in postmenopausal women, and
could therefore be provided as an alternative exercise.
PMID- 24348030
TI - Over diagnosis of chronic obstructive pulmonary disease in an underserved patient
population.
AB - INTRODUCTION: While cross-national studies have documented rates of chronic
obstructive pulmonary disease (COPD) misdiagnosis among patients in primary care,
US studies are scarce. Studies investigating diagnosis among uninsured patients
are lacking. OBJECTIVE: The purpose of this study is to identify patients who are
over diagnosed and thus, mistreated, for COPD in a federally qualified health
center. METHODS: A descriptive study was conducted for a retrospective cohort
from February 2011 to June 2012. Spirometry was performed by trained personnel
following American Thoracic Society recommendations. Patients were referred for
spirometry to confirm previous COPD diagnosis or to assess uncontrolled COPD
symptoms. Airway obstruction was defined as a forced expiratory volume in the
first second of expiration (FEV1) to forced vital capacity ratio less than 0.7.
Reversibility was defined as a postbronchodilator increase in FEV1 greater than
200 mL and greater than 12%. RESULTS: Eighty patients treated for a previous
diagnosis of COPD (n = 72) or on anticholinergic inhalers (n = 8) with no COPD
diagnosis were evaluated. The average age was 52.9 years; 71% were uninsured.
Only 17.5% (14/80) of patients reported previous spirometry. Spirometry revealed
that 42.5% had no obstruction, 22.5% had reversible obstruction, and 35% had non
reversible obstruction. CONCLUSION: Symptoms and smoking history are insufficient
to diagnose COPD. Prevalence of COPD over diagnosis among uninsured patient
populations may be higher than previously reported. Confirming previous COPD
diagnosis with spirometry is essential to avoid unnecessary and potentially
harmful treatment.
PMID- 24348031
TI - Risk assessment of readmissions following an initial COPD-related
hospitalization.
AB - BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is
a leading cause of hospitalizations and readmissions in the US. Reducing the
frequency of hospital readmission is a high priority of US health care
organizations and government agencies. This study evaluated the risk factors
associated with readmissions among commercially insured adults aged 40-65 years
in the US who were hospitalized for COPD. METHODS: This retrospective cohort
study used anonymized claims data from the Truven Health MarketScan(r) Commercial
Claims and Encounters database. The patients included were aged 40-65 years, had
an index hospitalization with a primary diagnosis of COPD between July 1, 2008
and June 30, 2010 (continuously enrolled 12 months before and after), and were
alive at hospital discharge. Patients with cystic fibrosis or tuberculosis or who
were transferred to another inpatient facility after hospital discharge were
excluded. All readmissions regardless of diagnosis, and separately a subset of
all readmissions that had COPD as a primary or secondary diagnosis (COPD
related), were examined. Univariate descriptive statistics and multivariable
regression methods were used. RESULTS: Of the 18,568 patients with index COPD
hospitalizations, 6,095 (32.83%) met the eligibility criteria. Of those, 503
(8.25%) were readmitted within the first 30 days post-index hospitalization and
2,527 (41.46%) within the first year (COPD-related 340 [5.58%] and 1,681
[27.58%], respectively). The median time to the first readmission post initial
discharge was 4.0 months, with a mean of 5.0 +/- 3.4 months. Multivariable
regression analyses showed that comorbid conditions and health care utilization
in the pre-index period were significant predictors for readmission both 30 and
90 days following index hospitalization. CONCLUSION: A relatively high
readmission rate was observed for patients aged 40-65 years. The results suggest
that attention to patient comorbidities and pre-index/index health care service
utilization may help identify hospitalized COPD patients at higher risk for
readmission.
PMID- 24348032
TI - Impact of night-time symptoms in COPD: a real-world study in five European
countries.
AB - BACKGROUND: Sleep quality is often poor in patients with chronic obstructive
pulmonary disease (COPD). A cross-sectional European survey investigated the
prevalence of night-time symptoms in COPD to evaluate the level of disconnect
between physician and patient perceptions of the presence of night-time symptoms,
and to compare the characteristics of patients with and without night-time
symptoms. METHODS: A total of 251 primary care physicians and 251 respiratory
specialists completed record forms on 2,807 patients with COPD. The forms
captured information on patient demographics, lung function, COPD severity, and
symptoms. Patients completed questionnaires on the time of day when their COPD
symptoms bothered them, and the impact of COPD on their ability to get up in the
morning and on sleep. Data were compared between groups (those with and without
night-time symptoms) using t-tests or Wilcoxon signed rank tests. The kappa
statistic was used to assess the level of disconnect between physician and
patient perceptions of the impact of night-time symptoms. RESULTS: Most patients
(78%) reported night-time disturbance. Patients with night-time symptoms
experienced more daytime breathlessness (mean modified Medical Research Council
dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months
(mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus
2.3 products) than those without. Concordance between the frequency of physician
reported (67.9% of patients) and patient-reported (68.5% of patients) night-time
symptoms was good. Physicians significantly underestimated the impact of COPD on
the patient's ability to get up in the morning and on sleep (fair-moderate
agreement). Physician-reported night-time symptoms were present for 41.2% of
patients who could be categorized by Global initiative for chronic Obstructive
Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk
group to 77.4% of those in the high-riskgroup. CONCLUSION: Patients with COPD
experience night-time symptoms regardless of GOLD group, that impact on their
ability to get up in the morning and on their sleep quality.
PMID- 24348033
TI - Use of a care bundle in the emergency department for acute exacerbations of
chronic obstructive pulmonary disease: a feasibility study.
AB - AIM: To determine the efficacy and usefulness of a chronic obstructive pulmonary
disease (COPD) care bundle designed for the initial management of acute
exacerbations of COPD and to assess whether it improves quality of care and
provides better outcomes. INTRODUCTION: The level of care provided in the
emergency department (ED) for COPD exacerbations varies greatly, and there is a
need for a more systematic, consistent, evidence-based quality improvement
approach to improve outcomes and costs. METHODS: A prospective before and after
study was carried out in a university teaching hospital. Fifty consecutive
patients were identified in the ED with COPD exacerbations and their management
was reviewed. Following the education of ED staff and the implementation of a
COPD care bundle, the outcome for 51 consecutive patients was analyzed. This COPD
care bundle consisted of ten elements considered essential to the management of
COPD exacerbations and was scored 0-10 according to the number of items on the
checklist implemented correctly. RESULTS: Following implementation, the mean
bundle score out of 10 improved from 4.6 to 7 (P<0.001). There was a significant
decrease in the unnecessary use of intravenous corticosteroids from 60% to 32%
(P=0.003) and also a marked improvement in the use of oxygen therapy, with
appropriate treatment increasing from 76% to 96% (P=0.003). Prophylaxis for
venous thromboembolism also improved from 54% to 73% (P=0.054). The 30-day
readmission rate did not significantly improve. CONCLUSION: The use of a bundle
improves the delivery of care for COPD exacerbations in the ED. There is more
appropriate use of therapeutic interventions, especially oxygen therapy and
intravenous corticosteroids.
PMID- 24348034
TI - Biosensor based on tyrosinase immobilized on a single-walled carbon nanotube
modified glassy carbon electrode for detection of epinephrine.
AB - A biosensor comprising tyrosinase immobilized on a single-walled carbon nanotube
modified glassy carbon electrode has been developed. The sensitive element, ie,
tyrosinase, was immobilized using a drop-and-dry method followed by cross
linking. Tyrosinase maintained high bioactivity on this nanomaterial, catalyzing
the oxidation of epinephrine to epinephrine-quinone, which was electrochemically
reduced (-0.07 V versus Ag/AgCl) on the biosensor surface. Under optimum
conditions, the biosensor showed a linear response in the range of 10-110 MUM.
The limit of detection was calculated to be 2.54 MUM with a correlation
coefficient of 0.977. The repeatability, expressed as the relative standard
deviation for five consecutive determinations of 10(-5) M epinephrine solution
was 3.4%. A good correlation was obtained between results obtained by the
biosensor and those obtained by ultraviolet spectrophotometric methods.
PMID- 24348036
TI - Human neural progenitor cells retain viability, phenotype, proliferation, and
lineage differentiation when labeled with a novel iron oxide nanoparticle, Molday
ION Rhodamine B.
AB - Ultrasmall superparamagnetic iron-oxide particles (USPIOs) loaded into stem cells
have been suggested as a way to track stem cell transplantation with magnetic
resonance imaging, but the labeling, and post-labeling proliferation, viability,
differentiation, and retention of USPIOs within the stem cells have yet to be
determined for each type of stem cell and for each type of USPIO. Molday ION
Rhodamine BTM (BioPAL, Worcester, MA, USA) (MIRB) has been shown to be a USPIO
labeling agent for mesenchymal stem cells, glial progenitor cells, and stem cell
lines. In this study, we have evaluated MIRB labeling in human neuroprogenitor
cells and found that human neuroprogenitor cells are effectively labeled with
MIRB without use of transfection reagents. Viability, proliferation, and
differentiation properties are unchanged between MIRB-labeled neuroprogenitors
cells and unlabeled cells. Moreover, MIRB-labeled human neuroprogenitor cells can
be frozen, thawed, and replated without loss of MIRB or even without loss of
their intrinsic biology. Overall, those results show that MIRB has advantageous
properties that can be used for cell-based therapy.
PMID- 24348035
TI - The effects of poly L-lactic acid nanofiber scaffold on mouse spermatogonial stem
cell culture.
AB - INTRODUCTION: A 3D-nanofiber scaffold acts in a similar way to the extracellular
matrix (ECM)/basement membrane that enhances the proliferation and self-renewal
of stem cells. The goal of the present study was to investigate the effects of a
poly L-lactic acid (PLLA) nanofiber scaffold on frozen-thawed neonate mouse
spermatogonial stem cells (SSCs) and testis tissues. METHODS: The isolated
spermatogonial cells were divided into six culture groups: (1) fresh
spermatogonial cells, (2) fresh spermatogonial cells seeded onto PLLA, (3) frozen
thawed spermatogonial cells, (4) frozen-thawed spermatogonial cells seeded onto
PLLA, (5) spermatogonial cells obtained from frozen-thawed testis tissue, and (6)
spermatogonial cells obtained from frozen-thawed testis tissue seeded onto PLLA.
Spermatogonial cells and testis fragments were cryopreserved and cultured for 3
weeks. Cluster assay was performed during the culture. The presence of
spermatogonial cells in the culture was determined by a reverse transcriptase
polymerase chain reaction for spermatogonial markers (Oct4, GFRalpha-1, PLZF,
Mvh(VASA), Itgalpha6, and Itgbeta1), as well as the ultrastructural study of cell
clusters and SSCs transplantation to a recipient azoospermic mouse. The
significance of the data was analyzed using the repeated measures and analysis of
variance. RESULTS: The findings indicated that the spermatogonial cells seeded on
PLLA significantly increased in vitro spermatogonial cell cluster formations in
comparison with the control groups (culture of SSCs not seeded on PLLA)
(P<=0.001). The viability rate for the frozen cells after thawing was 63.00% +/-
3.56%. This number decreased significantly (40.00% +/- 0.82%) in spermatogonial
cells obtained from the frozen-thawed testis tissue. Both groups, however, showed
in vitro cluster formation. Although the expression of spermatogonial markers was
maintained after 3 weeks of culture, there was a significant downregulation for
some spermatogonial genes in the experimental groups compared with those of the
control groups. Furthermore, transplantation assay and transmission electron
microscopy studies suggested the presence of SSCs among the cultured cells.
CONCLUSION: Although PLLA can increase the in vitro cluster formation of neonate
fresh and frozen-thawed spermatogonial cells, it may also cause them to
differentiate during cultivation. The study therefore has implications for SSCs
proliferation and germ cell differentiation in vitro.
PMID- 24348037
TI - Heuristic modeling of macromolecule release from PLGA microspheres.
AB - Dissolution of protein macromolecules from poly(lactic-co-glycolic acid) (PLGA)
particles is a complex process and still not fully understood. As such, there are
difficulties in obtaining a predictive model that could be of fundamental
significance in design, development, and optimization for medical applications
and toxicity evaluation of PLGA-based multiparticulate dosage form. In the
present study, two models with comparable goodness of fit were proposed for the
prediction of the macromolecule dissolution profile from PLGA micro- and
nanoparticles. In both cases, heuristic techniques, such as artificial neural
networks (ANNs), feature selection, and genetic programming were employed.
Feature selection provided by fscaret package and sensitivity analysis performed
by ANNs reduced the original input vector from a total of 300 input variables to
21, 17, 16, and eleven; to achieve a better insight into generalization error,
two cut-off points for every method was proposed. The best ANNs model results
were obtained by monotone multi-layer perceptron neural network (MON-MLP)
networks with a root-mean-square error (RMSE) of 15.4, and the input vector
consisted of eleven inputs. The complicated classical equation derived from a
database consisting of 17 inputs was able to yield a better generalization error
(RMSE) of 14.3. The equation was characterized by four parameters, thus feasible
(applicable) to standard nonlinear regression techniques. Heuristic modeling led
to the ANN model describing macromolecules release profiles from PLGA
microspheres with good predictive efficiency. Moreover genetic programming
technique resulted in classical equation with comparable predictability to the
ANN model.
PMID- 24348038
TI - Immobilized transferrin Fe3O4@SiO2 nanoparticle with high doxorubicin loading for
dual-targeted tumor drug delivery.
AB - Transferrin (Tf) was immobilized onto Fe3O4@SiO2 nanoparticles with high
doxorubicin (DOX) loading (TfDMP), for dual targeting of cancer, by chemically
coupling both Tf and DOX with dual-function magnetic nanoparticles (DMPs) using a
multi-armed crosslinker, poly-L-glutamic acid. With high trapping efficiency for
magnetic targeting, TfDMP exhibits a Tf receptor-targeting function. Moreover,
the DOX loading percentage of TfDMP is high, and can be controlled by adjusting
the reactant ratio. TfDMP presents a narrow size distribution, and is sensitive
to pH for drug release. Compared with DOX-coupled DMP without Tf modification
(DDMP), TfDMP exhibits enhanced uptake by Tf receptor-expressing tumor cells, and
displays stronger cancer cell cytotoxicity. This study provides an efficient
method for the dual-targeted delivery of therapeutic agents to tumors, with
controlled low carrier toxicity and high efficiency.
PMID- 24348039
TI - Evaluating the potential of poly(beta-amino ester) nanoparticles for
reprogramming human fibroblasts to become induced pluripotent stem cells.
AB - BACKGROUND: Gene delivery can potentially be used as a therapeutic for treating
genetic diseases, including neurodegenerative diseases, as well as an enabling
technology for regenerative medicine. A central challenge in many gene delivery
applications is having a safe and effective delivery method. We evaluated the use
of a biodegradable poly(beta-amino ester) nanoparticle-based nonviral protocol
and compared this with an electroporation-based approach to deliver episomal
plasmids encoding reprogramming factors for generation of human induced
pluripotent stem cells (hiPSCs) from human fibroblasts. METHODS: A polymer
library was screened to identify the polymers most promising for gene delivery to
human fibroblasts. Feeder-independent culturing protocols were developed for
nanoparticle-based and electroporation-based reprogramming. The cells
reprogrammed by both polymeric nanoparticle-based and electroporation-based
nonviral methods were characterized by analysis of pluripotency markers and
karyotypic stability. The hiPSC-like cells were further differentiated toward the
neural lineage to test their potential for neurodegenerative retinal disease
modeling. RESULTS: 1-(3-aminopropyl)-4-methylpiperazine end-terminated poly(1,4
butanediol diacry-late-co-4-amino-1-butanol) polymer (B4S4E7) self-assembled with
plasmid DNA to form nanoparticles that were more effective than leading
commercially available reagents, including Lipofectamine(r) 2000, FuGENE(r) HD,
and 25 kDa branched polyethylenimine, for nonviral gene transfer. B4S4E7
nanoparticles showed effective gene delivery to IMR-90 human primary fibroblasts
and to dermal fibroblasts derived from a patient with retinitis pigmentosa, and
enabled coexpression of exogenously delivered genes, as is needed for
reprogramming. The karyotypically normal hiPSC-like cells generated by
conventional electroporation, but not by poly(beta-amino ester) reprogramming,
could be differentiated toward the neuronal lineage, specifically
pseudostratified optic cups. CONCLUSION: This study shows that certain nonviral
reprogramming methods may not necessarily be safer than viral approaches and that
maximizing exogenous gene expression of reprogramming factors is not sufficient
to ensure successful reprogramming.
PMID- 24348040
TI - Why it is time to develop the use of cognitive event-related potentials in the
treatment of psychiatric diseases.
AB - The relapse rate for many psychiatric disorders is staggeringly high, indicating
that treatment methods combining psychotherapy with neuropharmacological
interventions are not entirely effective. Therefore, in psychiatry, there is a
current push to develop alternatives to psychotherapy and medication-based
approaches. Cognitive deficits have gained considerable importance in the field
as critical features of mental illness, and it is now believed that they might
represent valid therapeutic targets. Indeed, an increase in cognitive skills has
been shown to have a long-lasting, positive impact on the patients' quality of
life and their clinical symptoms. We hereby present four principal arguments
supporting the use of event-related potentials (ERP) that are derived from
electroencephalography, which allow the identification of specific neurocognitive
deficiencies in patients. These arguments could assist psychiatrists in the
development of individualized, targeted therapy, as well as a follow-up and
rehabilitation plan specific to each patient's deficit. Furthermore, they can be
used as a tool to assess the possible benefits of combination therapy, consisting
of medication, psychotherapy, and "ERP-oriented cognitive rehabilitation". Using
this strategy, specific cognitive interventions could be planned based on each
patient's needs, for an "individualized" or "personalized" therapy, which may
have the potential to reduce relapse rates for many psychiatric disorders. The
implementation of such a combined approach would require intense collaboration
between psychiatry departments, clinical neurophysiology laboratories, and
neuropsychological rehabilitation centers.
PMID- 24348041
TI - Influence of cerebellar stereotactic stimulation on left-right electrodermal
information transference in a patient with cerebral palsy.
AB - BACKGROUND AND OBJECTIVES: Recent evidence indicates that cerebral palsy is
connected to specific autonomic dysregulation between sympathetic and
parasympathetic efferent pathways, likely linked to hemispheric influences. These
findings suggest a hypothesis that contralateral interhemispheric disinhibition,
which may occur on various levels of brain processing including motor functions,
could be linked to specific functional dysregulation and structural lesions,
which may play a specific role in the modulation of autonomic functions and lead
to autonomic dysregulation in cerebral palsy. METHOD: With the aim of comparing
autonomic functions as they relate to interhemispheric modulatory influences
during therapeutically indicated stereotactic cerebellar stimulation, we have
performed bilateral electrodermal activity measurement and calculations of
pointwise transinformation (PTI) in a patient with cerebral palsy. Measurement
was performed during therapeutic deep cerebellar stimulation in two cerebellar
areas in anterior cerebellar lobe-culmen (left electrode) and central lobule
superior cerebellar peduncle (right electrode). RESULTS: The results indicate
that information transference (PTI) is able to distinguish the states related to
specific cerebellar stimulations and that lowest levels of the PTI have been
found during stimulation of the central lobule-superior cerebellar peduncle
(electrode deepest contact 1), indicating a significantly increased level of
inhibition between the left and right sides. CONCLUSION: The results may present
potentially useful clinical findings indicating that increased PTI calculated
from electrodermal activity could indirectly indicate disinhibitory activity as a
possible indicator of a failure of interhemispheric communication that could
explain some specific pathogenetic mechanisms in cerebral palsy. Nevertheless,
these results need detailed confirmation in further research, as well as reliable
clinical evaluation of their usefulness in the therapy of cerebral palsy.
PMID- 24348042
TI - Pseudobulbar affect: prevalence and management.
AB - Pseudobulbar affect (PBA) may occur in association with a variety of neurological
diseases, and so may be encountered in the setting of amyotrophic lateral
sclerosis, extrapyramidal and cerebellar disorders, multiple sclerosis, traumatic
brain injury, Alzheimer's disease, stroke, and brain tumors. The psychological
consequences and the impact on social interactions may be substantial. Although
it is most commonly misidentified as a mood disorder, particularly depression or
a bipolar disorder, there are characteristic features that can be recognized
clinically or assessed by validated scales, resulting in accurate identification
of PBA, and thus permitting proper management and treatment. Mechanistically, PBA
is a disinhibition syndrome in which pathways involving serotonin and glutamate
are disrupted. This knowledge has permitted effective treatment for many years
with antidepressants, particularly tricyclic antidepressants and selective
serotonin reuptake inhibitors. A recent therapeutic breakthrough occurred with
the approval by the Food and Drug Administration of a dextromethorphan/quinidine
combination as being safe and effective for treatment of PBA. Side effect
profiles and contraindications differ for the various treatment options, and the
clinician must be familiar with these when choosing the best therapy for an
individual, particularly elderly patients and those with multiple comorbidities
and concomitant medications.
PMID- 24348044
TI - Serum lipid profile and correlates in newly presenting Nigerians with arterial
hypertension.
AB - BACKGROUND: Arterial hypertension and dyslipidemia are modifiable cardiovascular
risk factors. The multiplicative effect of these risk factors may worsen the
atherogenic index of an individual. The objective of this study was to determine
the pattern and prevalence of dyslipidemia in newly presenting Nigerians with
arterial hypertension, as well as determine some of its correlates. METHODS: This
cross-sectional study compared 115 newly presenting, age- and sex-matched
individuals with arterial hypertension with 115 normotensive individuals. Fasting
lipids, total cholesterol (TC), triglycerides, high-density lipoprotein
cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting
plasma glucose were estimated. RESULTS: Patients with arterial hypertension had
higher body mass index (t=7.64; P=0.000), TC (t=2.95; P=0.006), and HDL-C (t=
5.18; P=0.000). The most common dyslipidemia was low HDL-C, found in both the
hypertensive (44.3%) and normotensive (20.9%) patients. The prevalence of
dyslipidemia in hypertensives and controls was 64% and 39%, respectively. In
hypertensive patients, TC correlated positively to diastolic blood pressure
(r=0.218; P=0.0019). Other positive correlates include LDL-C and age (r=0.217;
P=0.020) and fasting plasma glucose (r=0.202; P=0.030) and body mass index
(r=0.209; P=0.025). Among normotensive controls, TC correlated positively with
LDL-C (r=0.63; P=0.000) but correlated negatively with tri glycerides (r=-0.30;
P=0.001). CONCLUSION: Lipid abnormalities are common in newly presenting
Nigerians with arterial hypertension. Screening of these risk factors, promotion
of healthy lifestyle, and the institution of therapy is desirable to reduce their
multiplicative effects.
PMID- 24348045
TI - The GAIN Short Screener (GSS) as a Predictor of Future Arrest or Incarceration
Among Youth Presenting to Substance Use Disorder (SUD) Treatment.
AB - The National Institutes of Health (NIH) data harmonization project on existing
measures (www.phenx.org) has recommended the Global Appraisal of Individual Needs
(GAIN)-Short Screener (GSS) as one of the most reliable, valid, efficient, and
inexpensive general behavioral health screeners to quickly identify people with
internalizing and externalizing mental health disorders, substance use disorders,
and crime/violence problems. The present study examined how well the four GSS
screeners and their sum predict future arrest or incarceration among individuals
entering treatment for a substance use disorder. Using a cross-validation design,
a diverse sample of 6,815 youth with substance use disorders was split into a
development sample and a validation sample. Overall, results found the GSS's
crime and violence screener (CVScr) and the substance disorder screener (SDScr)
to be the two best predictors of arrest/incarceration within the 12 months
following treatment intake. Additionally, we found that these screeners could be
used to categorize individuals into three groups (low risk, moderate risk, high
risk) and this simplified classification had good predictive validity (Area Under
the Curve = 0.601). In sum, the GSS's predictive validity was similar to other
instruments that have been developed to predict risk for recidivism; however, the
GSS takes only a fraction of the time to collect (ie, approximately 2-3 minutes
for just these two screeners).
PMID- 24348043
TI - Vitamin E tocotrienol supplementation improves lipid profiles in chronic
hemodialysis patients.
AB - PURPOSE: Chronic hemodialysis patients experience accelerated atherosclerosis
contributed to by dyslipidemia, inflammation, and an impaired antioxidant system.
Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties.
However, the impact of dietary intervention with Vitamin E tocotrienols is
unknown in this population. PATIENTS AND METHODS: A randomized, double-blind,
placebo-controlled, parallel trial was conducted in 81 patients undergoing
chronic hemodialysis. Subjects were provided daily with capsules containing
either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg
tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints
included measurements of inflammatory markers (C-reactive protein and interleukin
6), oxidative status (total antioxidant power and malondialdehyde), lipid
profiles (plasma total cholesterol, triacylglycerols, and high-density
lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity
and apolipoprotein A1. RESULTS: TRF supplementation did not impact any
nutritional, inflammatory, or oxidative status biomarkers over time when compared
with the baseline within the group (one-way repeated measures analysis of
variance) or when compared with the placebo group at a particular time point
(independent t-test). However, the TRF supplemented group showed improvement in
lipid profiles after 12 and 16 weeks of intervention when compared with placebo
at the respective time points. Normalized plasma triacylglycerols (cf baseline)
in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after
12 and 16 weeks of intervention but no significant improvement was seen in the
placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol
was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and
week 16. The changes in the TRF group at week 12 and week 16 were associated with
higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl
ester transfer protein activity (P<0.001). CONCLUSION: TRF supplementation
improved lipid profiles in this study of maintenance hemodialysis patients. A
multi-centered trial is warranted to confirm these observations.
PMID- 24348046
TI - Synchronous BRAF(V600E) and MEK inhibition leads to superior control of murine
melanoma by limiting MEK inhibitor induced skin toxicity.
AB - The BRAF inhibitor (BRAFi) treatment has led to impressive responses in
BRAF(V600E) mutation-positive melanomas, but responses are not durable in many
patients. As most of the BRAFi escape mechanisms involve ERK reactivation,
combinations with MEK inhibitors (MEKi) are currently tested to improve BRAFi
mediated response durations. Additionally, such a combination is expected to
reduce MEKi-induced skin toxicities, as these drugs are thought to have
antagonistic effects on ERK activation in keratinocytes. However, preclinical in
vivo data exploring the combination of BRAFi and MEKi to achieve improved tumor
control in the absence of skin toxicities are limited. Using a murine
Tyr::CreER(T2);Pten(LoxP/LoxP);Braf(CA/+) melanoma model, we have determined the
effect of BRAFi and MEKi treatment and their combination on melanoma control and
occurrence of adverse events. We found that the MEKi dosed beyond the maximum
tolerable dose (MTD) led to stronger control of tumor growth than did the BRAFi,
but mice had to be removed from treatment because of skin toxicity. The
combination of BRAFi and MEKi reduced MEKi-associated skin toxicity. This allowed
high and long-term dosing of the MEKi, resulting in long-term tumor control. In
contrast to previous hypotheses, the addition of a BRAFi did not restore the MEKi
mediated downregulation of pERK1/2 in skin cells. Our data describe, for the
first time, the alleviation of MEKi-mediated dose-limiting toxicity by addition
of a BRAFi in a mouse melanoma model. Additional clinical Phase I studies should
be implemented to explore MEKi dosing beyond the single drug MTD in combination
with BRAFi.
PMID- 24348047
TI - Intraoperative radiotherapy in stage IIB adenocarcinoma of the uterine cervix: a
retrospective study.
AB - OBJECTIVES: Adenocarcinoma (AC) of the uterine cervix has a poor prognosis and is
usually fatal. The aim of this study was to evaluate the clinical outcome and
toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced
AC. METHODS: Twenty-seven women were treated with IOERT. Surgery consisted of
gross negative surgical margins in 19 patients, positive surgical margins in two
patients, and close surgical margins in six patients. Twenty-three patients
received chemotherapy. RESULTS: The 5-year overall survival and disease-free
survival rates were 21/27 (77.8%) and 19/27 (70.4%), respectively. A
significantly better survival rate was found in patients with AC compared to
patients with adenosquamous carcinoma. Tumor recurrence and metastasis were
observed in seven patients (25.9%). No central failure occurred whether or not
the resection margins were positive. Two (7.4%) patients developed peripheral
neurotoxicity. CONCLUSION: IOERT plus surgery may be feasible and effective with
a low risk of toxicity, even in patients with positive resection margins.
PMID- 24348048
TI - Gemcitabine and carboplatin demonstrate synergistic cytotoxicity in cervical
cancer cells by inhibiting DNA synthesis and increasing cell apoptosis.
AB - BACKGROUND: The present study aims to investigate the subunit expression and
enzyme activity of ribonucleotide reductase in cervical cancer patients, and
detect the combined effect of the ribonucleotide reductase inhibitor gemcitabine
and the chemotherapeutic agent carboplatin on cervical cancer cell lines.
METHODS: Using quantitative reverse transcription polymerase chain reaction,
Western blotting, and cytidine 5'-diphosphate reduction assays, we tested the
expression and activity of ribonucleotide reductase in cervical cancer patients.
The antitumor activity of gemcitabine and/or carboplatin treatments to SiHa and
CaSki human cervical cancer cell lines were assessed by Cell Counting Kit-8
viability assay, EdU incorporation assay, immunofluorescence assay, flow
cytometry assay, and Western blotting methods. Additionally, synergistic efficacy
was quantitatively analyzed using a combination index based on the Chou-Talalay
method. RESULTS: The mRNA levels of three ribonucleotide reductase subunits were
all upregulated in the cervical cancer tissues compared with normal tissues
(P<0.0001). Consistently, the protein expression and enzyme activity of
ribonucleotide reductase were also increased in the cervical cancer tissues.
Interestingly, gemcitabine inhibited DNA synthesis and carboplatin induced DNA
damage. Further, the combined drug regime had a significant synergistic effect on
inhibiting cervical cancer cell viability (log10[combination index] <0) via
enhanced DNA damage and cell apoptosis. CONCLUSION: The expression and activity
of ribonucleotide reductase was increased in cervical cancer. Our study
demonstrated the synergistic cytotoxicity of gemcitabine and carboplatin, through
inhibiting DNA synthesis and increasing cell apoptosis in cervical cancer cell
lines. This evidence might provide a rational clue of their combined application
to improve cervical cancer treatment.
PMID- 24348049
TI - The potential for targeting extracellular LOX proteins in human malignancy.
AB - The extracellular matrix (ECM) is the physical scaffold where cells are organized
into tissues and organs. The ECM may be modified during cancer to allow and
promote proliferation, invasion, and metastasis. The family of lysyl oxidase
(LOX) enzymes cross-links collagens and elastin and, therefore, is a central
player in ECM deposition and maturation. Extensive research has revealed how the
LOX proteins participate in every stage of cancer progression, and two family
members, LOX and LOX-like 2, have been linked to metastasis, the final stage of
cancer responsible for over 90% of cancer patient deaths. However, LOX
biosynthesis results in by-product with antiproliferative properties in certain
cancers, and LOX enzymes may have different effects depending on the molecular
network in which they are active. Therefore, the design of therapies targeting
the LOX family needs to be guided by the molecular makeup of the individual
disease and will probably require other agents to act on both the LOX enzymes and
their associated network.
PMID- 24348050
TI - Signal transduction molecule patterns indicating potential glioblastoma therapy
approaches.
AB - PURPOSE: The expression of an array of signaling molecules, along with the
assessment of real-time cell proliferation, has been performed in U87 glioma cell
line and in patients' glioblastoma established cell cultures in order to provide
a better understanding of cellular and molecular events involved in glioblastoma
pathogenesis. Experimental therapy was performed using a phosphatidylinositol-3'
kinase (PI3K) inhibitor. PATIENTS AND METHODS: xMAP technology was employed to
assess expression levels of several signal transduction molecules and real-time
xCELLigence platform for cell behavior. RESULTS: PI3K inhibition induced the most
significant effects on global signaling pathways in patient-derived cell
cultures, especially on members of the mitogen-activated protein-kinase family,
P70S6 serine-threonine kinase, and cAMP response element-binding protein
expression and further prevented tumor cell proliferation. CONCLUSION: The PI3K
pathway might be a prime target for glioblastoma treatment.
PMID- 24348051
TI - Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of
K-ras mutation.
AB - BACKGROUND: Bevacizumab plus chemotherapy prolongs progression-free survival
(PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although
there is strong evidence to suggest that the mutational status of the K-ras
oncogene has a role as a predictive factor for activity in patients treated with
cetuximab and panitumumab, few data have been obtained in patients treated with
bevacizumab. We conducted an additional retrospective analysis to investigate the
prognostic value of K-ras mutation relative to mCRC first-line treatment with
bevacizumab. MATERIALS AND METHODS: A total of 108 patients were retrospectively
reviewed. K-ras status was assessed in the overall population by sequencing.
Statistical association for PFS and OS was analyzed using the Kaplan-Meier
method, and the prognostic role of K-ras was determined using the logrank test.
RESULTS: Median PFS was 10 months both for patients with wild-type (WT) K-ras and
mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median
OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92;
P=0.70). A further analysis was carried out in the two groups according to
metastatic sites. No statistically significant difference in terms of PFS and OS
was demonstrated between WT K-ras and MT K-ras with liver metastases only and in
those with extrahepatic disease. CONCLUSION: Although further study is required,
our results seem to confirm that K-ras mutation does not have a prognostic role
in mCRC patients receiving first-line treatment with bevacizumab.
PMID- 24348052
TI - Sequential treatment of tyrosine kinase inhibitors and chemotherapy for EGFR
mutated non-small cell lung cancer: a meta-analysis of Phase III trials.
AB - BACKGROUND: This aim of this study was to compare the efficacy of first-line
tyrosine kinase inhibitor therapy followed, upon progression, by chemotherapy
with the reverse sequence in patients with EGFR-mutated non-small cell lung
cancer (NSCLC) in terms of overall survival. METHODS: We performed a meta
analysis of studies that met the following criteria: Phase III clinical trial
comparing the sequencing of epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitors with chemotherapy in the treatment of advanced EGFR-mutated
NSCLC; activating mutations reported; and availability of hazard ratio estimates
with 95% confidence intervals (CIs) for overall survival. RESULTS: Six clinical
trials were included in this study. The pooled hazard ratio for overall survival
of the EGFR-mutated population that completed sequential treatment was 1.03 (95%
CI 0.86-1.22, P=0.776). There was no statistically significant heterogeneity
between the studies (tau(2) =0; I(2)=0, 95% CI 0-0.37, P=0.548). Evidence of
marked publication bias for the two treatment sequences was insufficient
(P=0.145). CONCLUSION: In patients with advanced NSCLC and activating EGFR
mutations, first-line chemotherapy followed upon progression by a tyrosine kinase
inhibitor was not inferior in terms of overall survival compared with the inverse
sequence. This may serve as an indication that chemotherapy could be employed
initially if mutation testing results are unavailable.
PMID- 24348054
TI - The beta-lactamase inhibitor avibactam (NXL104) does not induce ampC beta
lactamase in Enterobacter cloacae.
AB - Induction of ampC beta-lactamase expression can often compromise antibiotic
treatment and is triggered by several beta-lactams (such as cefoxitin and
imipenem) and by the beta-lactamase inhibitor clavulanic acid. The novel beta
lactamase inhibitor avibactam (NXL104) is a potent inhibitor of both class A and
class C enzymes. The potential of avibactam for induction of ampC expression in
Enterobacter cloacae was investigated by ampC messenger ribonucleic acid
quantitation. Cefoxitin and clavulanic acid were confirmed as ampC inducers,
whereas avibactam was found to exert no effect on ampC expression. Thus,
avibactam is unlikely to diminish the activity of any partner beta-lactam
antibiotic against AmpC-producing organisms.
PMID- 24348053
TI - Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and beta-lactamase
inhibitor combination.
AB - The management of infections caused by multidrug-resistant Gram-negative
bacteria, particularly Pseudomonas aeruginosa, continues to be a significant
challenge to clinicians. Ceftolozane/tazobactam is a novel antibacterial and beta
lactamase-inhibitor combination that has shown appreciable activity against wild
type Enterobacteriaceae and potent activity against P. aeruginosa. Moreover,
ceftolozane/tazobactam has not demonstrated cross-resistance to other
antimicrobial classes, particularly those affected by extended-spectrum beta
lactamases, AmpC beta-lactamase, a loss in porin channels, or the overexpression
of efflux pumps in P. aeruginosa. Ceftolozane/tazobactam has completed two Phase
II clinical trials in complicated intra-abdominal and complicated urinary tract
infections. A Phase III, multicenter, prospective, randomized, open-label study
has been initiated to evaluate the safety and efficacy of ceftolozane/tazobactam
versus piperacillin/tazobactam for the treatment of ventilator-associated
pneumonia. A Medline search of articles from inception to May 2013 and references
for selected citations was conducted. Data from abstracts presented at
conferences were also appraised. This article reviews the antimicrobial,
pharmacokinetic, and pharmacodynamic profile of ceftolozane/tazobactam, and
discusses its potential role in therapy.
PMID- 24348055
TI - Comparison of the costs of nonoperative care to minimally invasive surgery for
sacroiliac joint disruption and degenerative sacroiliitis in a United States
Medicare population: potential economic implications of a new minimally-invasive
technology.
AB - INTRODUCTION: The economic burden associated with the treatment of low back pain
(LBP) in the United States is significant. LBP caused by sacroiliac (SI) joint
disruption/degenerative sacroiliitis is most commonly treated with nonoperative
care and/or open SI joint surgery. New and effective minimally invasive surgery
(MIS) options may offer potential cost savings to Medicare. METHODS: An economic
model was developed to compare the costs of MIS treatment to nonoperative care
for the treatment of SI joint disruption in the hospital inpatient setting in the
US Medicare population. Lifetime cost savings (2012 US dollars) were estimated
from the published literature and claims data. Costs included treatment, follow
up, diagnostic testing, and retail pharmacy pain medication. Costs of SI joint
disruption patients managed with nonoperative care were estimated from the 2005
2010 Medicare 5% Standard Analytic Files using primary International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
diagnosis codes 720.2, 724.6, 739.4, 846.9, or 847.3. MIS fusion hospitalization
cost was based on Diagnosis Related Group (DRG) payments of $46,700 (with major
complications - DRG 459) and $27,800 (without major complications - DRG 460),
weighted assuming 3.8% of patients have complications. MIS fusion professional
fee was determined from the 2012 Medicare payment for Current Procedural
Terminology code 27280, with an 82% fusion success rate and 1.8% revision rate.
Outcomes were discounted by 3.0% per annum. RESULTS: The extrapolated lifetime
cost of treating Medicare patients with MIS fusion was $48,185/patient compared
to $51,543/patient for nonoperative care, resulting in a $660 million savings to
Medicare (196,452 beneficiaries at $3,358 in savings/patient). Including those
with ICD-9-CM code 721.3 (lumbosacral spondylosis) increased lifetime cost
estimates (up to 478,764 beneficiaries at $8,692 in savings/patient). CONCLUSION:
Treating Medicare beneficiaries with MIS fusion in the hospital inpatient setting
could save Medicare $660 million over patients' lifetimes.
PMID- 24348056
TI - Health economic evidence of 5% lidocaine medicated plaster in post-herpetic
neuralgia.
AB - BACKGROUND: Post-herpetic neuralgia (PHN) is the most common and most
debilitating complication of herpes zoster, and involves considerable associated
costs. OBJECTIVE: This paper presents results from nine health economic studies
undertaken in eight European countries that compared lidocaine medicated plaster
with gabapentin and/or pregabalin in PHN. It aims to support the increasing need
for published cost-effectiveness data for health care decision-making processes
in Europe. METHODS: All studies were based on a similar core Markov model with
data derived from clinical trials, local Delphi panels, and official national
price and tariff lists. The main outcome measure was cost per quality-adjusted
life year gained; time without pain or intolerable adverse events was also
included as a secondary outcome measure. All studies focused on an elderly
population of patients with PHN who had insufficient pain relief with standard
analgesics and could not tolerate or had contraindications to tricyclic
antidepressants. RESULTS: Despite considerable differences in many of the
variables used, the results showed remarkable similarity and suggested that use
of lidocaine medicated plaster offered cost-savings in many of the countries
studied, where it proved a highly cost-effective alternative to both gabapentin
and pregabalin. CONCLUSION: Lidocaine medicated plaster is a cost-effective
alternative to gabapentin and pregabalin in the treatment of PHN. These savings
are largely the result of the superior safety profile of the lidocaine medicated
plaster.
PMID- 24348057
TI - C-QUALITY: cost and quality-of-life pharmacoeconomic analysis of antidepressants
used in major depressive disorder in the regional Italian settings of Veneto and
Sardinia.
AB - BACKGROUND: Major depression is a commonly occurring, seriously impairing, and
often recurrent mental disorder. Selective serotonin reuptake inhibitors (SSRIs)
and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the treatments most
commonly used for major depressive disorder. The objective of this study was to
assess the cost-effectiveness of SSRIs and SNRIs in the treatment of major
depressive disorder in two Italian regional settings, ie, Veneto and Sardinia.
METHODS: A decision analytic model was adapted from the Swedish Dental and
Pharmaceutical Benefits Agency to reflect current clinical practice in the
treatment of major depressive disorder in the most significant Italian regions.
This adaptation was possible as a result of collaboration with an expert panel of
Italian psychiatrists and health economists. The population comprised patients
with a first diagnosis of major depressive disorder and initiating one SSRI or
SNRI drug for the first time. The time frame used was 12 months. Efficacy and
utility data for the model were retrieved from the literature and validated by
the expert panel. Local data were used for resource utilization and for treatment
costs based on the perspective of each regional health service. Scenario analyses
and probabilistic sensitivity analyses were performed to test the robustness of
the model. RESULTS: Base case analysis showed that escitalopram is associated
with the largest health gain (in quality-adjusted life years) and a lower total
cost at one year for Sardinia (except for sertraline, against which it was cost
effective) and for Veneto, and therefore dominates the other treatment
strategies, given that more quality-adjusted life years are achieved at a lower
total cost. Scenario analyses and probabilistic sensitivity analyses support the
robustness of the model. CONCLUSION: The results indicate that escitalopram is
the most cost-effective pharmacologic treatment strategy for both regional health
services compared with all SSRIs and all SNRIs used in the first-line treatment
of major depressive disorder.
PMID- 24348058
TI - Effects of a recreational physical activity and healthy habits orientation
program, using an illustrated diary, on the cardiovascular risk profile of
overweight and obese schoolchildren: a pilot study in a public school in
Brasilia, Federal District, Brazil.
AB - INTRODUCTION: Educative strategies need to be adopted to encourage the
consumption of healthy foods and to promote physical activity in childhood and
adolescence. The effects of recreational physical activity and a health-habit
orientation program using an illustrated diary on the cardiovascular risk profile
of overweight and obese children was investigated. METHODS: The weight and height
of 314 schoolchildren aged between 9 and 11 years old, in a public school in
Brasilia, Federal District, Brazil, were recorded. According to the body mass
index (BMI) classification proposed by the World Health Organization, 84 were
overweight or obese for their age and sex. Of these children, 34 (40%)
participated in the study. Students were divided into two groups matched for sex,
age, BMI, percent body fat (%BF): the intervention group (IG, n = 17) and the
control group (CG, n = 17). The IG underwent a program of 10 weeks of exercise
with recreational activities and health-habit orientation using an illustrated
diary of habits, while no such interventions were used with the CG during the
study period. Before and after the intervention, the children's weight, height,
BMI, %BF, waist circumference (WC), maximum oxygen intake (VO2max), total
cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL),
triglycerides, glucose, eating habits, and physical activity level (PAL) were
assessed. In analyzing the data, we used descriptive statistics and paired and
unpaired t-tests, using a significance level of 0.05. For assessment of dietary
habits, a questionnaire, contingency tables, and the chi-squared test were used,
with <0.05 set as the significance level. RESULTS: After 10 weeks of
intervention, the IG showed a reduction in BMI (pre: 22.2 +/- 2.1 kg/m(2) versus
[vs] post: 21.6 +/- 2.1 kg/m(2), P < 0.01); WC (pre: 70.1 +/- 6.1 cm vs post:
69.1 +/- 5.8 cm, P < 0.01); %BF (pre: 29.2% +/- 4.6% vs post: 28.0% +/- 4.8%, P <
0.01); systolic blood pressure (P < 0.01); VO2max (P = 0.014); TC (P < 0.01); LDL
(P < 0.01); triglycerides (P < 0.01); and intake of candy (P < 0.01) and soda
drinks (P < 0.01), while an increase in the consumption of fruit (P < 0.01) and
PAL (P < 0.01) were observed. The CG did not show any change in the health
parameters assessed. CONCLUSION: The program was effective in reducing risk
factors for cardiovascular disease and the use of an illustrative diary may have
been the key to this result, since students were motivated to change their poor
eating habits and to increase their physical activity level.
PMID- 24348059
TI - SGLT-2 inhibitors and their potential in the treatment of diabetes.
AB - Diabetes remains a burgeoning global problem, necessitating ongoing efforts on
the part of pharmaceutical and device manufacturers, patients, and society to
curb the frightening trends in morbidity and mortality attributable to the
malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2
(SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more
physiological approach to glucose control. These agents lower glucose by
enhancing its excretion by blocking reabsorption in the renal tubules, thus
eliminating glucose from the body along with the molecules' attendant effects on
caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors
improve glucose control to an extent comparable to other hypoglycemic agents
while simultaneously reducing body weight, blood pressure, and cholesterol - an
admirable portfolio. One agent, canagliflozin, has recently been approved by the
US Food and Drug Administration (FDA) and two other agents have progressed
through Phase III trials, including dapagliflozin and empagliflozin.
Collectively, when used as monotherapy, these agents have demonstrated reductions
in hemoglobin A1c (HbA1c), body weight, and blood pressure of -0.34% to -1.03%,
2.0 to -3.4 kg, and -1.7 to -6.4 mmHg/-0.3 to -2.6 mmHg (systolic blood
pressure/diastolic blood pressure), respectively. SGLT-2 inhibitors have been
well tolerated, with hypoglycemia (0.9% to 4.3%) occurring infrequently in
clinical trials. Safety signals related to breast and bladder cancer have arisen
with dapagliflozin, though these are unsubstantiated and likely ascribed to the
presence of preexisting cancer. As these agents emerge, clinicians should embrace
the addition to the formulary for treating type 2 diabetes, but must also weight
the risk-benefit of this new class in deciding which patient types are most
likely to benefit from their novel mechanism of action.
PMID- 24348060
TI - The effects of diet- and diet plus exercise-induced weight loss on basal
metabolic rate and acylated ghrelin in grade 1 obese subjects.
AB - BACKGROUND: Diet and exercise are often prescribed as primary intervention
regarding obesity-related disorders. Additionally, recent studies have shown
beneficial effects of weight loss through diet and exercise in ghrelin
concentrations in obese subjects. The aim of this study was to evaluate the
effects of a 5% weight loss on lipid profile, resting metabolic rate (RMR), and
acylated ghrelin (AG) using two different methods of intervention (diet or diet
plus exercise). MATERIALS AND METHODS: Eighteen subjects (twelve women and six
men) aged 20-40 years with a body mass index of 30-34.9 kg/m(2) (grade 1 obesity)
were randomized into two intervention groups: diet (n=9) or diet plus exercise
(n=9). Both groups underwent treatment until 5% of the initial body weight was
lost. At baseline and upon completion, RMR and AG were analyzed. RESULTS: Both
groups showed a significant decrease in body fat percentage and fat mass. The
diet-plus-exercise group showed a decrease in AG (pre: 54.4+/-25.3 pg/mL and
post: 33.2+/-19.1 pg/mL) and an increase in RMR (pre: 1,363+/-379 kcal/day, post:
1,633+/-223 kcal/day). CONCLUSION: These data suggest that diet plus exercise
induced weight loss and had beneficial effects on AG concentration and RMR,
essential factors to ensure the benefits of a weight-loss program.
PMID- 24348061
TI - HbA1c for diagnosis of type 2 diabetes. Is there an optimal cut point to assess
high risk of diabetes complications, and how well does the 6.5% cutoff perform?
AB - Glycated hemoglobin (HbA1c) has recently been recommended for the diagnosis of
type 2 diabetes mellitus (T2DM) by leading diabetes organizations and by the
World Health Organization. The most important reason to define T2DM is to
identify subjects with high risk of diabetes complications who may benefit from
treatment. This review addresses two questions: 1) to assess from existing
studies whether there is an optimal HbA1c threshold to predict diabetes
complications and 2) to assess how well the recommended 6.5% cutoff of HbA1c
predicts diabetes complications. HbA1c cutoffs derived from predominantly cross
sectional studies on retinopathy differ widely from 5.2%-7.8%, and among other
reasons, this is due to the heterogeneity of statistical methods and differences
in the definition of retinopathy. From the few studies on other microvascular
complications, HbA1c thresholds could not be identified. HbA1c cutoffs make less
sense for the prediction of cardiovascular events (CVEs) because CVE risks depend
on various strong risk factors (eg, hypertension, smoking); subjects with low
HbA1c levels but high values of CVE risk factors were shown to be at higher CVE
risk than subjects with high HbA1c levels and low values of CVE risk factors.
However, the recommended 6.5% threshold distinguishes well between subjects with
and subjects without retinopathy, and this distinction is particularly strong in
severe retinopathy. Thus, in existing studies, the prevalence of any retinopathy
was 2.5 to 4.5 times as high in persons with HbA1c-defined T2DM as in subjects
with HbA1c <6.5%. To conclude, from existing studies, a consistent optimal HbA1c
threshold for diabetes complications cannot be derived, and the recommended 6.5%
threshold has mainly been brought about by convention rather than by having a
consistent empirical basis. Nevertheless, the 6.5% threshold is suitable to
detect subjects with prevalent retinopathy, which is the most diabetes specific
complication. However, most of the studies on associations between HbA1c and
microvascular diabetes complications are cross-sectional, and there is a need for
longitudinal studies.
PMID- 24348063
TI - Hyperuricemia and non-dipping blood pressure.
PMID- 24348062
TI - Effects of dopamine on leptin release and leptin gene (OB) expression in
adipocytes from obese and hypertensive patients.
AB - BACKGROUND: A reduction of dopaminergic (DAergic) activity with increased
prolactin levels has been found in obese and hypertensive patients, suggesting
its involvement as a pathophysiological mechanism promoting hypertension.
Similarly, leptin action increasing sympathetic activity has been proposed to be
involved in mechanisms of hypertension. The aim of this study was to analyze the
effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin
gene (OB) expression in adipocytes from obese and hypertensive patients. METHODS:
Leptin release and OB gene expression were analyzed in cultured adipocytes from
16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0
MUmol/L), NE (1.0 MUmol/L), insulin (0.1 MUmol/L), and prolactin (1.0 MUmol/L),
and from five nonobese and normotensive controls treated with DA (1 MUmol/L), NE
(1 MUmol/L), insulin (0.1 MUmol/L), and prolactin (1.0 MUmol/L). RESULTS: A dose
related reduction of leptin release and OB gene messenger ribonucleic acid
expression under different doses of DA was observed in adipocytes from obese
hypertensive patients. Whereas prolactin treatment elicited a significant
increase of both leptin release and OB gene expression, NE reduced these
parameters. Although similar effects of DA and NE were observed in adipocytes
from controls, baseline values in controls were reduced to 20% of the value in
adipocytes from obese hypertensive patients. CONCLUSION: These results suggest
that DAergic deficiency contributes to metabolic disorders linked to
hyperleptinemia in obese and hypertensive patients.
PMID- 24348064
TI - Prevalence of hypertension in three rural communities of Ife North Local
Government Area of Osun State, South West Nigeria.
AB - BACKGROUND: The prevalence of hypertension is increasing rapidly in sub-Saharan
Africa, but data are limited on hypertension prevalence. In addition, few
population-based studies have been conducted recently in Nigeria on the
prevalence and correlates of hypertension in both urban and rural communities.
Therefore, we determined the prevalence of hypertension in adults in the three
rural communities of Ipetumodu, Edunabon, and Moro, in South West Nigeria.
MATERIALS AND METHODS: One thousand adults between 15 and 90 years of age were
recruited into this cross-sectional study, over a 6-month period, using a
multistage proportional stratified random sampling technique. Sociodemographic
data and anthropometric variables were obtained, and resting blood pressure (BP)
was measured using an electronic sphygmomanometer. Diagnosis of hypertension was
based on the JNC VII guidelines, the WHO/ISH 1999 guidelines, and the BP
threshold of 160/95 mmHg. RESULTS: Four hundred and eighty-six men (48.6%) men
and 514 women (51.4%) participated in the study. Their mean age, weight, height,
and body mass index were 32.3+/-14.7 years, 62+/-13 kg, 1.5+/-0.1 m, and 23.02
kg/m(2), respectively. The prevalence of hypertension, based on the 140/90 mmHg
definition, was 26.4% (Male: 27.3%; Female: 25.4%). The prevalence of
hypertension, based on the 160/95 mmHg definition, was 11.8% (Male: 13.5%;
Female: 10.1%). There were significant positive correlations between BP and some
anthropometric indicators of obesity. CONCLUSION: The prevalence of hypertension
in the three rural communities was 26.4%, indicating a trend towards increasing
prevalence of hypertension. There was also a significant positive correlation
between anthropometric indicators of obesity and BP in this population.
PMID- 24348065
TI - Telephone-based anticoagulation management in the homebound setting: a
retrospective observational study.
AB - BACKGROUND: Anticoagulation management is currently performed through
anticoagulation clinics or self-managed with or without the help of medical
services. Homebound patients are a unique population that cannot utilize
anticoagulation clinics or self-testing. Telephone-based anticoagulation
management could be an alternative to the traditional methods of monitoring
warfarin in this subgroup. The objective of this retrospective, observational
study is to investigate the feasibility of warfarin management in homebound
patients. METHODS: This study was performed through the use of telephone-based
adjustments of warfarin dose based on an international normalized ratio (INR)
result. Four hundred forty-eight homebound patients referred to the
anticoagulation clinic at Staten Island University Hospital were visited at home
by a phlebotomist; a blood sample was drawn for initial laboratory testing. A
nurse practitioner then called the patient or designated person to relay the INR
result and to direct dosage adjustment. INR results and dosage changes were
entered into an electronic medical record and analyzed statistically. RESULTS:
The mean percentage of INR values in range was 58.39%. The mean time when the INR
was in the therapeutic range was 62.75%. The percent of patients who were
therapeutically controlled decreased as the number of medications increased. The
complication rate was 4% per patient year, with an equal distribution between
bleeding and clotting. These values compared favorably to other studies in which
monitoring was performed through anticoagulation clinics or self-monitoring. The
cost per visit at our anticoagulation clinic was found to be approximately $300
compared with $82 when utilizing our homebound service. CONCLUSION: Telephone
based management of warfarin therapy in the homebound setting is feasible. It can
lower the cost of health care expenditures compared to other modalities of
anticoagulation management.
PMID- 24348066
TI - The prevalence and reliability of self-reported penicillin allergy in a community
hospital.
AB - BACKGROUND: Penicillin (PCN) accounts for most cases of antibiotic allergies.
Reported PCN allergy deprives the patient from this class of antibiotics and
creates hesitancy in using other beta-lactam antibiotics. The aim of this study
is to report the prevalence of self-reported PCN allergy among adult patients
admitted to the hospital and to examine the probable validity of these reports.
METHODS: A questionnaire was conducted among 192 patients with self-reported PCN
allergy who were admitted to a community hospital between July 25, 2011 and
January 25, 2012. Patients admitted with an infection and treated with a beta
lactam were also followed until hospital discharge. RESULTS: The mean age of
patients at the time of their self-reported allergic reaction was 20.3 years. The
most common allergic symptoms reported in decreasing order of frequency were
itchy rash, angioedema, and urticaria. Based on analysis of the questionnaires,
121 patients (63.0%) had probable PCN allergy, 54 (28.1%) had possible PCN
allergy, and 17 (8.9%) were unlikely to have a PCN allergy. Fifty-one
participants (26.6%) had self-reported subsequent exposure to PCN in their life.
This subsequent exposure was well tolerated in 86.3% of the participants. Fifty
participants (25.9%) had self-reported subsequent exposure to a first generation
cephalosporin and it was well tolerated in 78.4% of them. CONCLUSION: Taking a
detailed history from patients with self-reported PCN allergy can help to
distinguish a true PCN allergy from a false positive report of allergy and hence
allow clinicians to use this important class of antibiotics when truly indicated.
PMID- 24348067
TI - Feasibility and analgesic efficacy of the transversus abdominis plane block after
single-port laparoscopy in patients having bariatric surgery.
AB - PURPOSE: The transversus abdominis plane (TAP) block is a technique increasingly
used for analgesia after surgery on the anterior abdominal wall. We undertook
this study to determine the feasibility and analgesic efficacy of ultrasound
guided TAP blocks in morbidly obese patients. We describe the dermatomal spread
of local anesthetic in TAP blocks administered, and test the hypothesis that TAP
blocks decrease visual analog scale (VAS) scores. PATIENTS AND METHODS: After
ethics committee approval and informed consent, 35 patients with body mass index
>35 undergoing single-port sleeve gastrectomy (SPSG) were enrolled. All patients
received balanced general anesthesia, followed by intravenous patient-controlled
analgesia (IV-PCA; hydromorphone) postoperatively; all reported VAS >3 upon
arrival to the recovery room. From the cohort of 35 patients having single-port
laparoscopy (SPL), a sealed envelope method was used to randomly select ten
patients to the TAP group and 25 patients to the control group. The ten patients
in the TAP group received ultrasound-guided TAP blocks with 30 mL of 0.2%
Ropivacaine injected bilaterally. The dermatomal distribution of the sensory
block (by pinprick test) was recorded. VAS scores for the first 24 hours after
surgery and opioid use were compared between the IV-PCA+TAP block and IV-PCA only
groups. RESULTS: Sensory block ranged from T5-L1. Mean VAS pain scores decreased
from 8 +/- 2 to 4 +/- 3 (P=0.04) within 30 minutes of TAP block administration.
Compared with patients given IV-PCA only, significantly fewer patients who
received TAP block had moderate or severe pain (VAS 4-10) after block
administration at 6 hours and 12 hours post-surgery. However, cumulative
consumption of hydromorphone at 24 hours after SPSG surgery was similar for both
groups. CONCLUSION: Ultrasound-guided TAP blocks in morbidly obese patients are
feasible and result in satisfactory analgesia following SPSG in the immediate
postoperative period.
PMID- 24348068
TI - Dengue: factors driving the emerging epidemic.
PMID- 24348069
TI - Epidemiology of idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause
that occurs in adults and has a poor prognosis. Its epidemiology has been
difficult to study because of its rarity and evolution in diagnostic and coding
practices. Though uncommon, it is likely underappreciated both in terms of its
occurrence (ie, incidence, prevalence) and public health impact (ie, health care
costs and resource utilization). Incidence and mortality appear to be on the
rise, and prevalence is expected to increase with the aging population. Potential
risk factors include occupational and environmental exposures, tobacco smoking,
gastroesophageal reflux, and genetic factors. An accurate understanding of its
epidemiology is important, especially as novel therapies are emerging.
PMID- 24348070
TI - Lifestyle factors among proton pump inhibitor users and nonusers: a cross
sectional study in a population-based setting.
AB - PURPOSE: Lifestyle factors may influence observed associations between proton
pump inhibitor (PPI) usage and health outcomes. The aim of the study reported
here was to examine characteristics and differences in lifestyle among PPI users
and nonusers. METHODS: This cross-sectional study utilized data from a 2006
population-based health survey of 21,637 persons in the Central Danish Region.
All persons using prescribed PPIs were identified through linkage to a population
based prescription database. Biometric measures and prevalence of smoking,
excessive alcohol consumption, diet, and physical exercise were analyzed,
comparing PPI users with nonusers. RESULTS: Among 10,129 (46.8%) male and 11,508
(53.2%) female survey respondents, 1,356 (13.4%) males and 1,691 (14.7%) females
reported ever use of PPIs. PPI users were more obese (16.7%) than nonusers
(13.1%), with an age- and sex-standardized prevalence ratio (PR) of 1.3 (95%
confidence interval [CI]: 1.2-1.4). The prevalence of smokers was also higher in
the PPI group (26.2% vs 22.3% [PR =1.2, 95% CI: 1.1-1.3]), as was the prevalence
of ex-smokers (41.0% vs 32.0% [PR =1.2, 95% CI: 1.1-1.2]). Unhealthy diet was
slightly more common among PPI users than among nonusers (15.4% vs 13.0%), with a
PR of 1.2 (95% CI: 1.1-1.3). Physical exercise level and alcohol consumption were
similar in the two groups. Hospital-diagnosed comorbidity was observed in 35% of
PPI users (a Charlson Comorbidity Index score of 1 or more) compared with only
15% among nonusers. CONCLUSION: PPI users are more obese, smoke more, and have
significantly more comorbidities than PPI nonusers. These data are important when
evaluating unmeasured confounding in observational studies of PPI effects.
PMID- 24348071
TI - Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort
of commercially insured individuals diagnosed with Crohn's disease in the United
States.
AB - BACKGROUND AND AIMS: Thiopurines, including 6-mercaptopurine (6-MP) and
azathioprine (AZA), are the mainstay of maintenance therapy for Crohn's disease
(CD). However, studies examining their effectiveness in routine practice among
diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA,
we described treatment patterns and changes in subsequent therapy. METHODS: Using
the Truven Health Analytics databases, we identified all individuals diagnosed
with CD and initiating 6-MP/AZA monotherapy from 2001-2008 (n=3,657). We
estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using
Kaplan-Meier methods, and identified predictors of treatment noncontinuation,
using multivariable Cox regression. Among the "noncontinuers," we described
subsequent patterns of maintenance therapy and summarized the diagnosis and
procedure codes and prescription drug claims preceding treatment discontinuation.
RESULTS: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age
<=18 years) and individuals with no prior anti-tumor necrosis factor (TNF) use
were more likely to continue 6-MP/AZA, while those dispensed more (>4) outpatient
prescriptions for any drug before initiation of 6-MP/AZA were less likely to
continue maintenance treatment. Overall, 1,128 (39%) and 105 (4%) individuals
experienced a clinical event potentially indicating active disease or 6-MP/AZA
intolerance prior to discontinuation, respectively. Most patients discontinued
therapy; among the remaining patients who failed to continue 6-MP/AZA, most
augmented with an anti-TNF. CONCLUSION: Most patients initiating 6-MP/AZA
monotherapy did not continue beyond 1 year. In contrast to trial evidence showing
1-year remission rates of 40%-80%, this study observed a lower effectiveness of 6
MP/AZA treatment, possibly due to differences in disease severity, patient
demographics, comorbidity, adherence, and health care utilization.
PMID- 24348072
TI - The risk of bleeding with duloxetine treatment in patients who use nonsteroidal
anti-inflammatory drugs (NSAIDs): analysis of placebo-controlled trials and post
marketing adverse event reports.
AB - PURPOSE: To assess the safety of duloxetine with regards to bleeding-related
events in patients who concomitantly did, versus did not, use nonsteroidal anti
inflammatory drugs (NSAIDs), including aspirin. METHODS: Safety data from all
placebo-controlled trials of duloxetine conducted between December 1993 and
December 2010, and post-marketing reports from duloxetine-treated patients in the
US Food and Drug Administration Adverse Event Reporting System (FAERS), were
searched for bleeding-related treatment-emergent adverse events (TEAEs). The
percentage of patients with bleeding-related TEAEs was summarized and compared
between treatment groups in all the placebo-controlled studies. Differences
between NSAID user and non-user subgroups from clinical trial data were analyzed
by a logistic regression model that included therapy, NSAID use, and therapy-by
NSAID subgroup interaction. In addition, to determine if higher duloxetine doses
are associated with an increased incidence of bleeding-related TEAEs, and whether
the use of concomitant NSAIDs might influence the dose effect if one exists,
placebo-controlled clinical trials with duloxetine fixed doses of 60 mg, 120 mg,
and placebo were analyzed. Also, the incidence of bleeding-related TEAEs reported
for duloxetine alone was compared with the incidence in patients treated with
duloxetine and concomitant NSAIDs. Finally, the number of bleeding-related cases
reported for duloxetine in the FAERS database was compared with the numbers
reported for all other drugs. RESULTS: Across duloxetine clinical trials, there
was a significantly greater incidence of bleeding-related TEAEs in duloxetine-
versus placebo-treated patients overall and also in those patients who did not
take concomitant NSAIDS, but no significant difference was seen among those
patients who did take concomitant NSAIDS. There was no significant difference in
the incidence of bleeding-related TEAEs in the subset of patients treated with
duloxetine 120 mg once daily versus those treated with 60 mg once daily
regardless of concomitant NSAID use. The combination of duloxetine and NSAIDs was
associated with a statistically significantly higher incidence of bleeding
related TEAEs compared with duloxetine alone. A similarly higher incidence of
bleeding-related TEAEs was seen in patients treated with placebo and concomitant
NSAIDs compared with placebo alone. Bleeding-related TEAEs reported in the FAERS
database were disproportionally more frequent for duloxetine taken with NSAIDs
compared with the full FAERS background, but there was no difference in the
reporting of bleeding-related TEAEs when the cases reported for duloxetine taken
with NSAIDs were compared against the cases reported for NSAIDs alone.
CONCLUSION: Concomitant use of NSAIDs was associated with a higher incidence of
bleeding-related TEAEs in clinical trials regardless of whether patients were
taking duloxetine or placebo; bleeding-related TEAEs did not appear to increase
along with duloxetine dose regardless of NSAID use. In spontaneously reported
post-marketing data, the combination of duloxetine and NSAID use was not
associated with an increased reporting of bleeding-related events when compared
to NSAID use alone.
PMID- 24348073
TI - Poor immunological recovery among severely immunosuppressed antiretroviral
therapy-naive Ugandans.
AB - INTRODUCTION: CD4 T lymphocytes remain the surrogate measure for monitoring HIV
progress in resource-limited settings. The absolute CD4 cell counts form the
basis for antiretroviral therapy (ART) initiation and monitoring among HIV
infected adults. However, the rate of CD4 cell change differs among patients, and
the factors responsible are inadequately documented. OBJECTIVE: This study
investigated the relationship between HIV severity and ART outcomes among ART
naive Ugandans, with the primary outcome of complete immunological recovery among
patients of different baseline CD4 counts. METHODS: Patients' records at two
HIV/ART sites - the Joint Clinic Research Centre (JCRC) in the Kampala region and
Mbarara Hospital in Western Uganda - were reviewed. Records of 426 patients -
68.3% female and 63.2% from JCRC - who initiated ART between 2002 and 2007 were
included. HIV severity was based on baseline CD4 cell counts, with low counts
considered as severe immunosuppression, while attaining 418 CD4 cells/MUL
signified complete immunological recovery. Incidence rates of complete
immunological recovery were calculated for, and compared between baseline CD4
cell categories: <50 with >=50, <100 with >=100, <200 with >=200, and >=200 with
>=250 cells/MUL. RESULTS: The incidence of complete immunological recovery was
158 during 791.9 person-years of observation, and patients with baseline CD4 >=
200 cells/MUL reached the end point of immunological recovery 1.89 times faster
than the patients with baseline CD4 < 200 cells/MUL. CD4 cell change also
differed by time, sex, and site, with a faster increase observed during the first
year of treatment. CD4 cell increase was faster among females, and among patients
from Mbarara. CONCLUSION: Initiating ART at an advanced HIV stage was the main
reason for poor immunological recovery among Ugandans. Earlier ART initiation
might lead to better immunological responses.
PMID- 24348074
TI - Intrauterine contraception after cesarean section and during lactation: a
systematic review.
AB - BACKGROUND: All postpartum women, including those who are breastfeeding or have
had a cesarean section, appear potentially suited to intrauterine contraception,
a long acting reversible contraceptive (LARC). Like any other method used after
delivery, it should not interfere with lactation or be affected by cesarean
section. STUDY DESIGN: We searched the MEDLINE, PubMed, Popline, Google Scholar,
and Clinicaltrials.gov databases from January 1968 through to December 2012.
Studies were included if they reported event rates in women who had a cesarean
section and event rates and clinical outcomes in lactating women or their infants
in the breastfeeding group. Summary odds ratios were not calculated because of
the diverse methods of reporting event rates in the cesarean section group and
the heterogeneity of the results in the breastfeeding group. RESULTS: We found 26
articles on event rates in interval and post-placental intrauterine device (IUD)
use, and 18 on event rates and clinical outcomes in breastfeeding IUD users. Four
prospective studies and one retrospective study showed an increased expulsion
rate in interval insertion. There were 19 studies, of which five were controlled
in post-placental IUD insertion after cesarean section. Four studies had
expulsion rates of 10 or more per 100 woman-years of use and 15 expulsion rates
below 10 per 100 woman-years of use. Three studies showed that event rates for
lactating IUD users are the same as those for non-lactating users. Fifteen
controlled studies showed that the IUD had no effect on milk production and seven
of these showed no effect on infant growth. Pharmacovigilance databases report an
increased rate of IUD perforations in lactating women, while the event rate
studies report that insertion is generally easier and less painful than expected.
These were uncontrolled reports. CONCLUSION: The IUD is a long-acting reversible
method of contraception with expulsion rates of 5-15 per 100 woman-years of use
when used as a post-placental method immediately after cesarean section. As an
interval procedure (6 or more weeks after cesarean section) it appears to have a
high expulsion rate (5% or higher) notably in older devices. The IUD does not
affect breastfeeding and is easy to insert in these women, but appears to be
associated with a higher perforation rate (>1 per 100). Providers should not be
deterred from using this contraception method, especially in developing
countries, but should be attentive to preventing these potential problems.
PMID- 24348075
TI - Chronic khat (Catha edulis) and alcohol marginally alter complete blood counts,
clinical chemistry, and testosterone in male rats.
AB - INTRODUCTION: Khat (Catha edulis) is a recreational psychoactive drug with
psychostimulant properties. While the use of this drug is widespread in eastern
Africa, including the Horn of Africa, surveys and anecdotal data show that its
use has become cosmopolitan, with users now living in Europe and North America as
well. Recent data in Uganda suggest an increasing pattern of simultaneous khat
and ethanol use particularly among young adults. However, the effects of this
pattern of use remain largely unknown, even though long-term use of either drug
alone is known to be harmful. The aim of this study was to examine the toxic
effects of simultaneous chronic administration of khat and ethanol on
hematological parameters, clinical chemistry, and testosterone in a rat model.
METHODS: Adult male Sprague-Dawley rats were randomly assigned to one of six dose
groups: 2 g/kg khat; 4 g/kg khat; 4 g/kg ethanol; combined khat and ethanol (4
g/kg each); control; and an untreated group. Treatments were given by gavage
twice daily for 28 days, followed by determination of hematological parameters,
blood clinical chemistry, and testosterone. RESULTS: Ethanol alone significantly
reduced platelet counts compared to control-, untreated and low-dose khat-treated
rats; conversely low-dose khat significantly increased both the hemoglobin and
hematocrit values, while ethanol alone also significantly increased the
hemoglobin value compared to controls. Simultaneous khat and ethanol
administration per se did not produce more toxic consequences in chronic use than
either drug alone. CONCLUSION: Chronic short-term khat use and ethanol dependence
individually produce note-worthy effects on the blood, but not on clinical
chemistry or testosterone. Chronic short-term combined khat and ethanol use does
not produce more toxic effects compared to use of either drug alone. This
provides an opportunity for appropriate clinical interventions to avert the
chronic long-term effects that result from use of these drugs of abuse.
PMID- 24348076
TI - Clinical utility of implantable neurostimulation devices in the treatment of
chronic migraine.
AB - Chronic migraine is a disabling disorder that is costly to individuals and
society. Occipital nerve stimulation has been used to treat refractory cases of
primary headache disorders including drug-resistant chronic cluster headaches and
chronic migraine. The Food and Drug Administration (FDA) off-labeled application
of equipment used for peripheral nerve (occipital) stimulation is borrowed from
FDA-labeled spinal cord stimulation. Manufacturer-sponsored randomized trials
include a feasibility study (ONSTIM-Medtronic) and a safety and efficacy study
(St Jude). A non-industry sponsored prospective, randomized crossover study by
Serra and Marchiotretto suggests improved quality of life and a significant
reduction in medication use. Though preliminary studies suggest occipital nerve
stimulation is safe and efficacious in treating chronic migraine headache,
complication rates, including lead migration, lead fracture, and surgical site
infections remain high. Further studies are needed to demonstrate long-term
outcomes, while improved surgical techniques and site-specific equipment are
needed to minimize complications.
PMID- 24348077
TI - System for simultaneous measurements of bilaterally symmetrical acupoints
multifrequency impedances.
AB - Devices which can obtain comparable bilaterally symmetrical acupoints (BSA)
multifrequency impedances (MFI) are often needed in the detection of the energy
balance states of acupoints in traditional Chinese medicine. To satisfy these
needs, a two-channel impedance measurement system has been introduced which is
capable of accurately and simultaneously measuring BSA MFI. The system includes a
set of five electrodes, two of which are injected with exciting current signal to
synchronously and equally excite BSA; the other three electrodes are used as
sensors to simultaneously sense the response signal from both sides. The system
also includes a PC-based time-domain signal testing platform with arbitrary
current waveform generation and three channels (one exciting current and two
response voltages) simultaneously sampling, and a set of MFI simultaneously
unbiased computing algorithms based on special odd multisine current signal
input. Preliminary validating experiments suggest that the system allows accurate
and synchronous measurement of BSA MFI at least in the frequency range of 10 Hz
to 60 kHz, and the obtained BSA MFI are well comparable.
PMID- 24348078
TI - Implantable cardioverter defibrillator and inappropriate therapy: "black box"
examination yielded both human and technical causes.
AB - We report on a 70-year-old male patient who was recipient of GEM III DR 7275
Cardioverter Defibrillator, and who presented with inappropriate shocks. The
patient had a documented slow ventricular tachycardia (VT), and the device was
programmed to detect VT at rates >100 bpm, fast VT (FVT, via VT) at rates >150
bpm, and ventricular fibrillation (VF) at rates >188 bpm. After detection of FVT,
efficient therapy was delivered; however, this was immediately followed by
multiple inappropriate therapies. Inappropriate therapies were discussed, with a
focus on programming features.
PMID- 24348079
TI - Lipoprotein glomerulopathy associated with a mutation in apolipoprotein e.
AB - Lipoprotein glomerulopathy is a pathological condition characterized by lipid
accumulation in the glomerular capillaries that has been associated with the
presence of rare mutants of apolipoprotein E (ApoE). We describe a 51-year-old
Italian patient presenting Type III hyperlipidemia and proteinuria in whom renal
biopsy showed capillary ectasia and intraluminal lipid deposits, suggesting the
diagnosis of lipoprotein glomerulopathy. The patient, who had elevated plasma
ApoE level, was found to be heterozygous for a mutation in ApoE (Arg150Cys),
designated apoEMODENA. This mutation induces the formation of ApoE dimers that
are detectable under non-reducing conditions. Treatment with hypolipidemic drugs
did not result in a complete remission of the proteinuria and was accompanied by
a slow but progressive worsening of renal function with the persistence of
intracapillary lipid thrombi. The introduction of low-density lipoprotein
aphaeresis combined with a more aggressive lipid lowering and antihypertensive
therapy resulted in the remission of proteinuria and a substantial improvement of
renal function. Switching from low-density lipoprotein aphaeresis to plasma
filtration did not result in an equivalent control of renal damage. The patient
died of intracranial hemorrhage during an acute episode of malignant
hypertension.
PMID- 24348080
TI - Epidemiology of Primary Hyperparathyroidism and its Non-classical Manifestations
in the City of Recife, Brazil.
AB - Before the introduction of routine measurements of serum calcium in ambulatory
services, PHTP (primary hyperparathyroidism) was symptomatic with classic bone
disease (known as osteitis fibrosa cystica) nephrolithiasis, and acute
neuropsychiatric syndrome with severe hypercalcemia. Currently, PHPT presents few
unspecific symptoms. This cross-sectional study was conducted from December 1,
2007, through August 31, 2008 to estimate the prevalence of primary
hyperparathyroidism and to describe the clinical and laboratory characteristics
of patients receiving ambulatory care. From 4207 patients, we found a prevalence
of PHTP of 0.78 (95% confidence interval [CI], 0.52-1.04) of which 81.8% were
asymptomatic and 18.2% symptomatic. The female:male ratio was 7.2:1, and 89.7% of
the women were postmenopausal. Mean age was 61.12 +/- 15.73 years, mean serum
calcium was 10.63 +/- 1.33 mg/dL, and mean serum parathyroid hormone (PTH) was
182.48 +/- 326.51 pg/mL. We found a high prevalence of PHTP at reference centers
and a high prevalence of hypertension and type 2 diabetes.
PMID- 24348081
TI - Atypical mechanism of glucose modulation by colesevelam in patients with type 2
diabetes.
AB - Colesevelam's glucose-lowering mechanism of action is not completely understood.
Clinical trials of colesevelam suggest that its mechanism, and often adverse
effects, differ from those of other oral antidiabetes drugs. Colesevelam does not
affect insulin sensitivity (unlike thiazolidinediones), insulin secretion (unlike
sulfonylureas and meglitinides), or early insulin response or glucagon (unlike
dipeptidyl peptidase-4 inhibitors). Colesevelam may have some effect on glucose
absorption, but likely via a different mechanism than alpha-glucosidase
inhibitors. Colesevelam and metformin have similarities regarding hepatic glucose
production, but divergent effects on gluconeogenesis versus glycogenolysis,
suggesting differing mechanisms of drug action for improving glycemic control.
Colesevelam is thought to be a portal glucagon-like peptide-1 (GLP-1)
secretagogue with primarily hepatic effects. Bile acid binding by colesevelam
leads to TGR5 activation, increased secretion of GLP-1 or other incretins, and
inhibition of hepatic glycogenolysis. Colesevelam's mechanism of action appears
to be atypical of other antidiabetes medications, making it a potentially
suitable component of many combination regimens in the treatment of type 2
diabetes.
PMID- 24348083
TI - An aftereffect of adaptation to mean size.
AB - The visual system rapidly represents the mean size of sets of objects. Here, we
investigated whether mean size is explicitly encoded by the visual system, along
a single dimension like texture, numerosity, and other visual dimensions
susceptible to adaptation. Observers adapted to two sets of dots with different
mean sizes, presented simultaneously in opposite visual fields. After adaptation,
two test patches replaced the adapting dot sets, and participants judged which
test appeared to have the larger average dot diameter. They generally perceived
the test that replaced the smaller mean size adapting set as being larger than
the test that replaced the larger adapting set. This differential aftereffect
held for single test dots (Experiment 2) and high-pass filtered displays
(Experiment 3), and changed systematically as a function of the variance of the
adapting dot sets (Experiment 4), providing additional support that mean size is
adaptable, and therefore explicitly encoded dimension of visual scenes.
PMID- 24348082
TI - Mothers' and Fathers' Negative Responsibility Attributions and Perceptions of
Children's Problem Behavior.
AB - Parents' negative responsibility attributions about their child's misbehavior are
related to a perception that the child has more behavior problems. The current
study used a dyadic framework to explore how mothers' and fathers' attributions
relate to their own perceptions and to their partner's perceptions of the child's
externalizing problems. Participants included 102 couples interviewed when
children were 7 years old. Results confirmed that mothers reported more
externalizing behavior problems in their children than did fathers, and fathers
of boys reported more child behavior problems than fathers of girls. Dyadic
analyses suggested that parents' negative responsibility attributions of the
child's behavior were associated with greater perceptions of child externalizing
problems on behalf of parents and their partners.
PMID- 24348084
TI - The Neural Fate of Individual Item Representations in Visual Working Memory.
PMID- 24348085
TI - Measuring eddy covariance fluxes of ozone with a slow-response analyser.
AB - Ozone (O3) fluxes above a temperate mountain grassland were measured by means of
the eddy covariance (EC) method using a slow-response O3 analyser. The resultant
flux loss was corrected for by a series of transfer functions which model the
various sources of high- and, in particular, low-pass filtering. The resulting
correction factors varied on average between 1.7 and 3.5 during night and day
time, respectively. A cospectral analysis confirmed the accuracy of this
approach. O3 fluxes were characterised by a comparatively large random
uncertainty, which during daytime typically amounted to 60 %. EC O3 fluxes were
compared against O3 flux measurements made concurrently with the flux-gradient
(FG) method. The two methods generally agreed well, except for a period between
sun rise and early afternoon, when the FG method was suspected of being affected
by the presence of photochemical sources/sinks. O3 flux magnitudes and deposition
velocities determined with the EC method compared nicely with the available
literature from grassland studies. We conclude that our understanding of the
causes and consequences of various sources of flux loss (associated with any EC
system) has sufficiently matured so that also less-than-ideal instrumentation may
be used in EC flux applications, albeit at the cost of relatively large empirical
corrections.
PMID- 24348087
TI - A war over mental health professionalism: Scientology versus psychiatry.
AB - Over 60 years ago, founder L. Ron Hubbard began what has become Scientology's
greatest battle. Scientology emerged from Dianetics, which Hubbard hoped would
replace the psychiatric profession. In this article, we discuss how Scientology
attempted to position itself as a rival profession to psychiatry and the
consequences of those attempts. Scientology's battle with psychiatry gained some
success from the social conditions during which it emerged, but it continues in a
time that has seen increasing success with various psychiatric treatments. As
such, Scientology's direct influence on the psychiatric profession may be
difficult to measure, but its actions have coincided with substantial challenges
to psychiatry.
PMID- 24348086
TI - Addressing extrema and censoring in pollutant and exposure data using mixture of
normal distributions.
AB - BACKGROUND: Volatile organic compounds (VOC), which include many hazardous
chemicals, have been used extensively in personal, commercial and industrial
products. Due to the variation in source emissions, differences in the settings
and environmental conditions where exposures occur, and measurement issues,
distributions of VOC concentrations can have multiple modes, heavy tails, and
significant portions of data below the method detection limit (MDL). These issues
challenge standard parametric distribution models needed to estimate the
exposures, even after log-transformation of the data. METHODS: This paper
considers mixture of distributions that can be directly applied to concentration
and exposure data. Two types of mixture distributions are considered: the
traditional finite mixture of normal distributions, and a semi-parametric
Dirichlet process mixture (DPM) of normal distributions. Both methods are
implemented for a sample data set obtained from the Relationship between Indoor,
Outdoor and Personal Air (RIOPA) study. Performance is assessed based on goodness
of-fit criteria that compare the closeness of the density estimates with the
empirical density based on data. The goodness-of-fit for the proposed density
estimation methods are evaluated by a comprehensive simulation study. RESULTS:
The finite mixture of normals and DPM of normals have superior performance when
compared to the single normal distribution fitted to log-transformed exposure
data. The advantages of using these mixture distributions are more pronounced
when exposure data have heavy tails or a large fraction of data below the MDL.
Distributions from the DPM provided slightly better fits than the finite mixture
of normals. Additionally, the DPM method avoids certain convergence issues
associated with the finite mixture of normals, and adaptively selects the number
of components. CONCLUSIONS: Compared to the finite mixture of normals, DPM of
normals has advantages by characterizing uncertainty around the number of
components, and by providing a formal assessment of uncertainty for all model
parameters through the posterior distribution. The method adapts to a spectrum of
departures from standard model assumptions and provides robust estimates of the
exposure density even under censoring due to MDL.
PMID- 24348088
TI - Large Covariance Estimation by Thresholding Principal Orthogonal Complements.
AB - This paper deals with the estimation of a high-dimensional covariance with a
conditional sparsity structure and fast-diverging eigenvalues. By assuming sparse
error covariance matrix in an approximate factor model, we allow for the presence
of some cross-sectional correlation even after taking out common but unobservable
factors. We introduce the Principal Orthogonal complEment Thresholding (POET)
method to explore such an approximate factor structure with sparsity. The POET
estimator includes the sample covariance matrix, the factor-based covariance
matrix (Fan, Fan, and Lv, 2008), the thresholding estimator (Bickel and Levina,
2008) and the adaptive thresholding estimator (Cai and Liu, 2011) as specific
examples. We provide mathematical insights when the factor analysis is
approximately the same as the principal component analysis for high-dimensional
data. The rates of convergence of the sparse residual covariance matrix and the
conditional sparse covariance matrix are studied under various norms. It is shown
that the impact of estimating the unknown factors vanishes as the dimensionality
increases. The uniform rates of convergence for the unobserved factors and their
factor loadings are derived. The asymptotic results are also verified by
extensive simulation studies. Finally, a real data application on portfolio
allocation is presented.
PMID- 24348089
TI - Piecing Together Cell-like Systems.
AB - Several laboratories are pursuing the synthesis of cellular systems from
different directions, including those that begin with simple chemicals to those
that exploit existing cells. The methods that begin with nonliving components
tend to focus on mimicking specific features of life, such as genomic
replication, protein synthesis, sensory systems, and compartment formation,
growth, and division. Conversely, the more prevalent synthetic biology approaches
begin with something that is already alive and seek to impart new behavior on
existing cells. Here we discuss advances in building cell-like systems that mimic
key features of life with defined components.
PMID- 24348090
TI - Interlaboratory comparison of size measurements on nanoparticles using
nanoparticle tracking analysis (NTA).
AB - One of the key challenges in the field of nanoparticle (NP) analysis is in
producing reliable and reproducible characterisation data for nanomaterials. This
study looks at the reproducibility using a relatively new, but rapidly adopted,
technique, Nanoparticle Tracking Analysis (NTA) on a range of particle sizes and
materials in several different media. It describes the protocol development and
presents both the data and analysis of results obtained from 12 laboratories,
mostly based in Europe, who are primarily QualityNano members. QualityNano is an
EU FP7 funded Research Infrastructure that integrates 28 European analytical and
experimental facilities in nanotechnology, medicine and natural sciences with the
goal of developing and implementing best practice and quality in all aspects of
nanosafety assessment. This study looks at both the development of the protocol
and how this leads to highly reproducible results amongst participants. In this
study, the parameter being measured is the modal particle size.
PMID- 24348091
TI - Development of novel anti-Kv 11.1 antibody-conjugated PEG-TiO2 nanoparticles for
targeting pancreatic ductal adenocarcinoma cells.
AB - Titanium dioxide (TiO2) has been widely used in many nanotechnology areas
including nanomedicine, where it could be proposed for the photodynamic and
sonodynamic cancer therapies. However, TiO2 nanoformulations have been shown to
be toxic for living cells. In this article, we report the development of a new
delivery system, based on nontoxic TiO2 nanoparticles, further conjugated with a
monoclonal antibody against a novel and easily accessible tumor marker, e.g., the
Kv 11.1 potassium channel. We synthesized, by simple solvothermal method,
dicarboxylic acid-terminated PEG TiO2 nanocrystals (PEG-TiO2 NPs). Anti-Kv 11.1
monoclonal antibodies (Kv 11.1-Mab) were further linked to the terminal
carboxylic acid groups. Proper conjugation was confirmed by X-ray photoelectron
spectroscopy analysis. Kv 11.1-Mab-PEG-TiO2 NPs efficiently recognized the
specific Kv 11.1 antigen, both in vitro and in pancreatic ductal adenocarcinoma
(PDAC) cells, which express the Kv 11.1 channel onto the plasma membrane. Both
PEG TiO2 and Kv 11.1-Mab-PEG-TiO2 NPs were not cytotoxic, but only Kv 11.1-Mab
PEG-TiO2 NPs were efficiently internalized into PDAC cells. Data gathered from
this study may have further applications for the chemical design of
nanostructures to be applied for therapeutic purposes in pancreatic cancer.
PMID- 24348092
TI - Beyond the Divinyl Ketone: Innovations in the Generation and Nazarov Cyclization
of Pentadienyl Cation Intermediates.
AB - The requirement for new strategies for synthesizing five-membered carbocycles has
driven an expansion in the study of the Nazarov cyclization. This renewed
interest in the reaction has led to the discovery of several interesting new
methods for generating the pentadienyl cation intermediate central to the
cyclization. Methods reviewed include carbon-heteroatom ionization,
functionalization of a double bond, nucleophilic addition, or electrocyclic ring
opening. Additional variations employ unconventional substrates to produce novel
pentacycles, such as the iso- and imino-Nazarov. Herein, we provide an overview
of these unconventional, yet highly useful versions of the Nazarov cyclization.
PMID- 24348093
TI - Close encounters of the third domain: the emerging genomic view of archaeal
diversity and evolution.
AB - The Archaea represent the so-called Third Domain of life, which has evolved in
parallel with the Bacteria and which is implicated to have played a pivotal role
in the emergence of the eukaryotic domain of life. Recent progress in genomic
sequencing technologies and cultivation-independent methods has started to
unearth a plethora of data of novel, uncultivated archaeal lineages. Here, we
review how the availability of such genomic data has revealed several important
insights into the diversity, ecological relevance, metabolic capacity, and the
origin and evolution of the archaeal domain of life.
PMID- 24348094
TI - The common ancestor of archaea and eukarya was not an archaeon.
AB - It is often assumed that eukarya originated from archaea. This view has been
recently supported by phylogenetic analyses in which eukarya are nested within
archaea. Here, I argue that these analyses are not reliable, and I critically
discuss archaeal ancestor scenarios, as well as fusion scenarios for the origin
of eukaryotes. Based on recognized evolutionary trends toward reduction in
archaea and toward complexity in eukarya, I suggest that their last common
ancestor was more complex than modern archaea but simpler than modern eukaryotes
(the bug in-between scenario). I propose that the ancestors of archaea (and
bacteria) escaped protoeukaryotic predators by invading high temperature
biotopes, triggering their reductive evolution toward the "prokaryotic" phenotype
(the thermoreduction hypothesis). Intriguingly, whereas archaea and eukarya share
many basic features at the molecular level, the archaeal mobilome resembles more
the bacterial than the eukaryotic one. I suggest that selection of different
parts of the ancestral virosphere at the onset of the three domains played a
critical role in shaping their respective biology. Eukarya probably evolved
toward complexity with the help of retroviruses and large DNA viruses, whereas
similar selection pressure (thermoreduction) could explain why the archaeal and
bacterial mobilomes somehow resemble each other.
PMID- 24348096
TI - Recent Progress in Rett Syndrome and MeCP2 Dysfunction: Assessment of Potential
Treatment Options.
AB - Synaptic communication is highly regulated process of contact between cells
allowing information to be stored and modified. Synaptic formation and maturation
is the result of interactions between intrinsic genetic/molecular factors and the
external environment to establish the communication in the brain. One disorder
associated with faulty synapse communication is Rett Syndrome (RTT). RTT is the
leading form of severe MR in females, affecting approximately 1:10,000 females
worldwide, without predisposition to any particular racial or ethnic group.
Mutations in MECP2, the gene encoding methyl-CpG-binding protein-2, have been
identified in more than 95% of individuals with RTT. Birth and the milestones of
early development appear to be normal in individuals with RTT until approximately
6-18 months when in the subsequent months and years that follows, physical,
motor, and social-cognitive development enter a period of regression. The
clinical management of these individuals is extremely multifaceted, relying on
collaborations of specialists and researchers from many different fields. In this
critical literature review, we provide an overview of Rett Syndrome, from patient
to pathophysiology with a therapeutic summary of clinical trials in RTT and
preclinical studies using mouse and cell models of RTT.
PMID- 24348095
TI - Early Detection of Huntington Disease.
AB - Huntington disease (HD) is a devastating illness, although its autosomal dominant
genetic transmission allows a unique opportunity to study apparently healthy
individuals before manifest disease. Attempts to study early disease are not
unique in neurology (e.g., Mild Cognitive Impairment, Vascular Cognitive
Impairment), but studying otherwise-healthy appearing individuals who will go on
with nearly 99% certainty to manifest the symptoms of brain disease does provide
distinct but valuable information about the true natural history of the disease.
The field has witnessed an explosion of research examining possible early
indicators of HD during what is now referred to as the "prodrome" of HD. A NIH
study in its ninth year (PREDICT-HD) has offered a glimpse into the transition
from an apparently healthy state to an obviously diseased state, and can serve as
a model for many other genetic diseases, both neurological and non-neurological.
PMID- 24348098
TI - The water balance of grassland ecosystems in the Austrian Alps.
AB - The altitudinal variation of precipitation, evapotranspiration and runoff was
quantified at 16 different grassland sites between 580 and 2550 m a.s.l. in the
Austrian Alps. Along this altitudinal transect annual evapotranspiration
decreased from roughly 690 mm at low elevation sites to 210 - 220 mm at the upper
limit of the alpine grassland belt. A detailed analysis of the data showed that
the observed reduction in the annual sum of evapotranspiration could be mainly
explained by the altitudinal decline of the length of the snow free period (i.e.
the vegetation period). Daily mean sums of evapotranspiration showed no
altitudinal trend and averaged 2.2 mm d-1 independent of elevation, although the
leaf area index, growing season mean air temperature, and vapour pressure deficit
declined with increasing altitude. As precipitation increased with elevation,
evapotranspiration seems to be of secondary importance when compared to runoff.
Inter-annual variability of evapotranspiration was fairly low across contrasting
dry and wet years (coefficient of variation = 7 %), indicating that even during
dry years water availability was not limiting evapotranspiration.
PMID- 24348099
TI - Tools of the Trade: Planned Missing Data Designs for Research in Cognitive
Development.
AB - Data collection can be the most time- and cost-intensive part of developmental
research. This article describes some long-proposed but little-used research
designs that have the potential to maximize data quality (reliability and
validity) while minimizing research cost. In planned missing data designs,
missing data are used strategically to improve the validity of data collection in
one of two ways. Multi-form designs allow one to increase the number of measures
assessed on each participant without increasing each participant's burden. Two
method measurement designs allow one to reap the benefits of a cost-intensive
gold-standard measure, using a larger sample size made possible by a rougher,
cheaper measure. We explain each method using examples relevant to cognitive
development research. With the use of analysis methods that produce unbiased
results, planned missing data designs are an efficient way to manage cost,
improve data quality, and reduce participant fatigue and practice effects.
PMID- 24348097
TI - PTEN phosphatase-independent maintenance of glandular morphology in a predictive
colorectal cancer model system.
AB - Organotypic models may provide mechanistic insight into colorectal cancer (CRC)
morphology. Three-dimensional (3D) colorectal gland formation is regulated by
phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell
division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study
investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic
functions in 3D models and assessed translational relevance in human studies.
Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In
translational studies, apical aPKC activity readout was assessed against apical
membrane (AM) orientation and gland morphology in 3D models and human CRC. We
found that catalytically active or inactive PTEN constructs containing an intact
C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium
binding region 3 membrane-binding loop (M-CBR3) were ineffective. The isolated
PTEN C2 domain (C2) accumulated in membrane fractions, but C2 M-CBR3 remained in
cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation
and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of
apical phospho-aPKC correlated with that of Na(+)/H(+) exchanger regulatory
factor-1 (NHERF-1) in the 3D model. Apical NHERF-1 intensity thus provided
readout of apical aPKC activity and associated with glandular morphology in the
model system and human colon. Low apical NHERF-1 intensity in CRC associated with
disruption of glandular architecture, high cancer grade, and metastatic
dissemination. We conclude that the membrane-binding function of the
catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics
and gland formation in a highly relevant 3D CRC morphogenesis model system.
PMID- 24348100
TI - Estimation and Selection via Absolute Penalized Convex Minimization And Its
Multistage Adaptive Applications.
AB - The l1-penalized method, or the Lasso, has emerged as an important tool for the
analysis of large data sets. Many important results have been obtained for the
Lasso in linear regression which have led to a deeper understanding of high
dimensional statistical problems. In this article, we consider a class of
weighted l1-penalized estimators for convex loss functions of a general form,
including the generalized linear models. We study the estimation, prediction,
selection and sparsity properties of the weighted l1-penalized estimator in
sparse, high-dimensional settings where the number of predictors p can be much
larger than the sample size n. Adaptive Lasso is considered as a special case. A
multistage method is developed to approximate concave regularized estimation by
applying an adaptive Lasso recursively. We provide prediction and estimation
oracle inequalities for single- and multi-stage estimators, a general selection
consistency theorem, and an upper bound for the dimension of the Lasso estimator.
Important models including the linear regression, logistic regression and log
linear models are used throughout to illustrate the applications of the general
results.
PMID- 24348101
TI - Creating Mechanisms for Meaningful Collaboration Between Members of Urban
Communities and University-Based HIV Prevention Researchers.
AB - This article provides a description of a Community/University Collaborative
Board, a formalized partnership between representatives from an inner-city
community and university-based researchers. This Collaborative Board oversees a
number of research projects focused on designing, delivering and testing family
based HIV prevention and mental health focused programs to elementary and junior
high school age youth and their families. The Collaborative Board consists of
urban parents, school staff members, representatives from community-based
agencies and university-based researchers. One research project, the CHAMP
(Collaborative HIV prevention and Adolescent Mental health Project) Family
Program Study, an urban, family-based HIV prevention project will be used to
illustrate how the Collaborative Board oversees a community-based research study.
The process of establishing a Collaborative Board, recruiting members and
developing subcommittees is described within this article. Examples of specific
issues addressed by the Collaborative Board within its subcommittees,
Implementation, Finance, Welcome, Research, Grant writing, Curriculum, and
Leadership, are detailed in this article along with lessons learned.
PMID- 24348102
TI - The Persistence of Segregation in the 21st Century Metropolis.
AB - The traditional black-white color line in the American metropolis is being
replaced by a more complex pattern of color lines involving multiple groups with
different racial and ethnic origins. The consequences are positive in some
respects, but they do not overcome the continuing barriers to equal opportunity.
The degree of segregation has receded from the near-apartheid that was created in
the black ghettos of Northern cities in the middle decades of the last century.
Yet the experience of segregation continues to impact blacks of all economic
classes. Today's color lines also involve Hispanics and Asians. The multiethnic
metropolis is fostering a degree of neighborhood diversity that used to be quite
rare. At the same time all-minority areas, now including blacks, Hispanics, and
sometimes Asians, continue to be reproduced, and the disparities in community
resources between white and minority neighborhoods remain deeply entrenched.
PMID- 24348104
TI - EEG Wave of the Future: The Video-EEG and fMRI Suite?
PMID- 24348103
TI - Why is there still doubt to cut it out?
AB - Surgical treatment for epilepsy has made tremendous strides in the past few
decades as a result of advances in neurodiagnostics-particularly structural and
functional neuroimaging-and improved surgical techniques. This has not only
resulted in better outcomes with respect to epileptic seizures and quality of
life, and reduced surgical morbidity and mortality, but it has also increased the
population of patients now considered as surgical candidates, particularly in the
pediatric age range, and enhanced cost-effectiveness sufficient to make surgical
treatment available to countries with limited resources. Yet surgical treatment
for epilepsy remains arguably the most underutilized of all accepted medical
interventions. In the United States, less than 1% of patients with
pharmacoresistant epilepsy are referred to epilepsy centers. Although the number
of epilepsy surgery centers has increased appreciably over the past two decades,
the number of therapeutic surgical procedures performed for epilepsy has not
increased at all. For patients who are referred, the average delay from onset of
epilepsy to surgery is more than 20 years-too late for many to avoid a lifetime
of disability or premature death. Not only has there been no consistent message
to convince neurologists and primary care physicians to refer patients for
surgery, but the increase in epilepsy surgery centers in the United States has
appeared to result in a divergence of approaches to surgical treatment. Efforts
are still needed to further improve the safety and efficacy of surgical
treatment, including the identification of biomarkers that can reliably determine
the extent of the epileptogenic region; however, the greatest benefits would
derive from increasing access for potential surgical candidates to epilepsy
surgery facilities. Information is needed to determine why appropriate surgical
referrals are not being made. Consensus conferences are necessary to resolve
controversies that still exist regarding presurgical evaluation and surgical
approaches. Standards should be established for certifying epilepsy centers as
recommended by the Institute of Medicine's report on epilepsy. Finally, the
epilepsy community should not be promoting epilepsy surgery per se but instead
emphasize that epilepsy centers do more than epilepsy surgery, promoting the
message: All patients with disabling pharmacoresistant seizures deserve
evaluation by specialists at epilepsy centers who can provide a variety of
advanced diagnostic and therapeutic services.
PMID- 24348105
TI - Tuber or Not Tuber: The Question of Epileptogenic Lesions in Tuberous Sclerosis
Complex (TSC).
PMID- 24348106
TI - Women with epilepsy planning pregnancy: we can improve outcomes by improving
care.
PMID- 24348107
TI - Ghee whiz! The growing evidence for the benefits of the modified atkins diet.
PMID- 24348108
TI - Hemispherectomy: the full half of the glass.
PMID- 24348109
TI - Shocking new insights into the epileptic trait.
PMID- 24348110
TI - Treatment of super-refractory status epilepticus: the sooner the better with less
adverse effects.
PMID- 24348111
TI - Chopping Out CHOP Chops the Fate of Neurons.
PMID- 24348112
TI - Algal proteins illuminate epilepsy.
PMID- 24348113
TI - Waking up the dormant dentate gyrus.
PMID- 24348114
TI - Is focal cortical dysplasia an infectious disease?
PMID- 24348116
TI - Submit Topics for 2014 IW and CIW Programs.
PMID- 24348115
TI - Seizure-induced newborn neurons might not be so bad after all.
PMID- 24348117
TI - Managing common complex symptomatic epilepsies: tumors and trauma: american
epilepsy society - 2012 annual course summary.
PMID- 24348118
TI - Seizures, Cerebral Shutdown, and SUDEP.
AB - Several potential pathophysiologic phenomena, including "cerebral shutdown," are
postulated to be responsible for SUDEP. Since the evidence for a seizure-related
mechanism is strong, a poor understanding of the physiology of human seizure
termination is a major handicap. However, rather than a failure of a single
homeostatic mechanism, such as postictal arousal, it may be a "perfect storm"
created by the lining up of a several factors that lead to death.
PMID- 24348119
TI - Serotonin: The Anti-SuddenDeathAmine?
AB - Sudden unexpected death in epilepsy (SUDEP) is an exceptionally difficult
condition to study in humans. Therefore, translational research in animal models
has been very important in defining pathophysiological mechanisms of death and
identifying potential treatments. These models are helping define whether the
primary mechanism of death is cardiac or respiratory. They have also identified a
link to the serotonergic system of the brainstem; this, in turn, led to
recognition that SUDEP and sudden infant death syndrome (SIDS) may share a common
final pathway in the sequence of events that lead to death.
PMID- 24348120
TI - "TOR"-ing Down the Dentate Gate in Temporal Lobe Epilepsy.
PMID- 24348121
TI - The right cells, the right place, the right result: transplants to alleviate
seizures take a step forward.
PMID- 24348122
TI - Sudden unexpected death in dravet syndrome.
PMID- 24348123
TI - Recipes for making human interneurons from stem cells require multiple factors,
careful timing, and long maturation periods.
PMID- 24348125
TI - Are HFOs Still UFOs? The Known and Unknown About High Frequency Oscillations in
Epilepsy Surgery.
PMID- 24348124
TI - Perampanel: a selective AMPA antagonist for treating seizures.
AB - Perampanel is a selective, noncompetitive AMPA receptor antagonist that has
recently been approved for treating localization-related epilepsy. This article
reviews the pharmacology, clinical development, efficacy, and safety/tolerability
of perampanel.
PMID- 24348126
TI - Predicting seizures: are we there yet?
PMID- 24348127
TI - Levetiracetam: more evidence of safety in pregnancy.
PMID- 24348128
TI - In utero valproate exposure and autism: long suspected, finally proven.
PMID- 24348129
TI - EEG and clinical features of childhood absence predict clinical outcomes.
PMID- 24348130
TI - Cortical hyperexcitability: a new biomarker in generalized epilepsy syndromes.
PMID- 24348131
TI - Serotonin and epilepsy: the story continues.
PMID- 24348134
TI - Taking the "Pulse" of Our Society with Q-PULSE.
PMID- 24348132
TI - Issues in Clinical Epileptology: A View from the Bench. A Festschrift in Honor of
Philip A. Schwartzkroin, PhD.
PMID- 24348135
TI - The Changing Face of Epileptology? Results of the Initial Q-PULSE Survey.
PMID- 24348133
TI - Evidence-based guideline update: vagus nerve stimulation for the treatment of
epilepsy: report of the guideline development subcommittee of the american
academy of neurology.
AB - OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy
and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as
adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We
reviewed the literature and identified relevant published studies. We classified
these studies according to the American Academy of Neurology evidence-based
methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95%
confidence interval [CI] 50%-59%) of 470 children with partial or generalized
epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction
in 55% (95% CI 46%-64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4
Class III studies). VNS is associated with an increase in >=50% seizure frequency
reduction rates of ~7% from 1 to 5 years postim-plantation (2 Class III studies).
VNS is associated with a significant improvement in standard mood scales in 31
adults with epilepsy (2 Class III studies). Infection risk at the VNS
implantation site in children is increased relative to that in adults (odds ratio
3.4, 95% CI 1.0-11.2). VNS is possibly effective for seizures (both partial and
generalized) in children, for LGS-associated seizures, and for mood problems in
adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS:
VNS may be considered for seizures in children, for LGS-associated seizures, and
for improving mood in adults with epilepsy (Level C). VNS may be considered to
have improved efficacy over time (Level C). Children should be carefully
monitored for site infection after VNS implantation. Neurology(r) 2013;81:1-7.
PMID- 24348136
TI - An efficient and self-adapted approach to the sharpening of color images.
AB - An efficient approach to the sharpening of color images is proposed in this
paper. For this, the image to be sharpened is first transformed to the HSV color
model, and then only the channel of Value will be used for the process of
sharpening while the other channels are left unchanged. We then apply a proposed
edge detector and low-pass filter to the channel of Value to pick out pixels
around boundaries. After that, those pixels detected as around edges or
boundaries are adjusted so that the boundary can be sharpened, and those nonedge
pixels are kept unaltered. The increment or decrement magnitude that is to be
added to those edge pixels is determined in an adaptive manner based on global
statistics of the image and local statistics of the pixel to be sharpened. With
the proposed approach, the discontinuities can be highlighted while most of the
original information contained in the image can be retained. Finally, the
adjusted channel of Value and that of Hue and Saturation will be integrated to
get the sharpened color image. Extensive experiments on natural images will be
given in this paper to highlight the effectiveness and efficiency of the proposed
approach.
PMID- 24348137
TI - An effective hybrid firefly algorithm with harmony search for global numerical
optimization.
AB - A hybrid metaheuristic approach by hybridizing harmony search (HS) and firefly
algorithm (FA), namely, HS/FA, is proposed to solve function optimization. In
HS/FA, the exploration of HS and the exploitation of FA are fully exerted, so
HS/FA has a faster convergence speed than HS and FA. Also, top fireflies scheme
is introduced to reduce running time, and HS is utilized to mutate between
fireflies when updating fireflies. The HS/FA method is verified by various
benchmarks. From the experiments, the implementation of HS/FA is better than the
standard FA and other eight optimization methods.
PMID- 24348138
TI - Root growth and enzymes related to the lignification of maize seedlings exposed
to the allelochemical L-DOPA.
AB - L-3,4-Dihydroxyphenylalanine (L-DOPA) is a known allelochemical exuded from the
roots of velvet bean (Mucuna pruriens L. Fabaceae). In the current work, we
analyzed the effects of L-DOPA on the growth, the activities of phenylalanine
ammonia-lyase (PAL), tyrosine ammonia-lyase (TAL), and peroxidase (POD), and the
contents of phenylalanine, tyrosine, and lignin in maize (Zea mays) roots. Three
day-old seedlings were cultivated in nutrient solution with or without 0.1 to 2.0
mM L-DOPA in a growth chamber (25 degrees C, light/dark photoperiod of 12/12, and
photon flux density of 280 MU mol m(-2) s(-1)) for 24 h. The results revealed
that the growth (length and weight) of the roots, the PAL, TAL, and soluble and
cell wall-bound POD activities decreased, while phenylalanine, tyrosine, and
lignin contents increased after L-DOPA exposure. Together, these findings showed
the susceptibility of maize to L-DOPA. In brief, these results suggest that the
inhibition of PAL and TAL can accumulate phenylalanine and tyrosine, which
contribute to enhanced lignin deposition in the cell wall followed by a reduction
of maize root growth.
PMID- 24348139
TI - Association of FAS and FAS ligand genes polymorphism and risk of systemic lupus
erythematosus.
AB - FAS/FASL pathway plays a critical role in maintaining peripheral immune
tolerance; therefore, the apoptosis genes, Fas and Fas ligand (FasL), could be
suitable candidate genes in human SLE susceptibility. MATERIALS AND METHODS: In
this case-control study, 106 SLE patients and 149 sex, age, and ethnicity matched
healthy controls were genotyped for the Fas A-670G and FasLC-844T polymorphisms
by polymerase chain reaction-restriction fragment length polymorphism method (PCR
RFLP). RESULTS: The frequency of -670AA genotype was significantly higher in SLE
patients than control group and the risk of SLE was 2.1-fold greater in subjects
with AA genotype (P=0.03). The frequency of -670A allele was significantly higher
in SLE patients than in controls too (58% versus 49%, P=0.03). The -844CC
genotype frequency was significantly higher in SLE patients than in healthy
controls and the risk of SLE was 2.8-fold greater in these subjects (P=0.01). The
C allele frequency was significantly higher in patients than in controls (69%
versus 49%, P=0.001). Increased SLE risk was observed in individuals with
combined effect of Fas-670AA and FasL-844CC genotypes (P=0.001). CONCLUSION: Fas
670AA and FasL-844CC genotypes were associated with SLE risk, and combined effect
of -670AA and -844CC genotypes might increase SLE susceptibility.
PMID- 24348140
TI - Drinking water fluoride levels for a city in northern Mexico (durango) determined
using a direct electrochemical method and their potential effects on oral health.
AB - Fluoride is ingested primarily through consuming drinking water. When drinking
water contains fluoride concentrations>0.7 parts per million (ppm), consuming
such water can be toxic to the human body; this toxicity is called "fluorosis."
Therefore, it is critical to determine the fluoride concentrations in drinking
water. The objective of this study was to determine the fluoride concentration in
the drinking water of the city of Durango. The wells that supply the drinking
water distribution system for the city of Durango were studied. One hundred
eighty-nine (189) water samples were analyzed, and the fluoride concentration in
each sample was quantified as established by the law NMX-AA-077-SCFI-2001. The
fluoride concentrations in such samples varied between 2.22 and 7.23 ppm with a
4.313+/-1.318 ppm mean concentration. The highest values were observed in the
northern area of the city, with a 5.001+/-2.669 ppm mean value. The samples
produced values that exceeded the national standard for fluoride in drinking
water. Chronic exposure to fluoride at such concentrations produces harmful
health effects, the first sign of which is dental fluorosis. Therefore, it is
essential that the government authorities implement water defluoridation programs
and take preventative measures to reduce the ingestion of this toxic halogen.
PMID- 24348141
TI - Deterministic sensing matrices in compressive sensing: a survey.
AB - Compressive sensing is a sampling method which provides a new approach to
efficient signal compression and recovery by exploiting the fact that a sparse
signal can be suitably reconstructed from very few measurements. One of the most
concerns in compressive sensing is the construction of the sensing matrices.
While random sensing matrices have been widely studied, only a few deterministic
sensing matrices have been considered. These matrices are highly desirable on
structure which allows fast implementation with reduced storage requirements. In
this paper, a survey of deterministic sensing matrices for compressive sensing is
presented. We introduce a basic problem in compressive sensing and some
disadvantage of the random sensing matrices. Some recent results on construction
of the deterministic sensing matrices are discussed.
PMID- 24348142
TI - Dynamic behavior for an SIRS model with nonlinear incidence rate and treatment.
AB - This paper considers an SIRS model with nonlinear incidence rate and treatment.
It is assumed that susceptible and infectious individuals have constant
immigration rates. We investigate the existence of equilibrium and prove the
global asymptotical stable results of the endemic equilibrium. We then obtained
that the model undergoes a Hopf bifurcation and existences a limit cycle. Some
numerical simulations are given to illustrate the analytical results.
PMID- 24348143
TI - Quantification of the dental morphology of orangutans.
AB - Orangutans are believed to have close biological affinities to humans. Teeth
being the hardest tissue provide useful information on primate evolution.
Furthermore, knowledge of the pulp chamber and root canal morphology is important
for dental treatment. A female Bornean orangutan and a Sumatran male orangutan
skull were available for this study. Both of their dentitions, comprising 50
teeth, were scanned employing the cone-beam computed tomography for both metrical
and nonmetrical analyses. Measurements included tooth and crown length, root
length, enamel covered crown height, root canal length (posterior teeth), length
of pulpal space (anterior teeth), and root canal width. Nonmetrical parameters
included number of canals per root, number of foramina in each root, and root
canal morphology according to Vertucci's classification. It was found that the
enamel covered crown height was the longest in the upper central incisors
although the canine was the longest amongst the anterior teeth. Both the upper
premolars were three-rooted while the lower second premolar of the Sumatran
orangutan was two-rooted, with two foramina. The mandibular lateral incisors of
the Bornean orangutan were longer than the central incisors, a feature similar to
humans. In addition, secondary dentine deposition was noticed, a feature
consistent with aged humans.
PMID- 24348145
TI - Retracted: Recent advances in DENV receptors.
PMID- 24348144
TI - Perceived barriers to healthy eating and physical activity among adolescents in
seven Arab countries: a cross-cultural study.
AB - OBJECTIVE: To highlight the perceived personal, social, and environmental
barriers to healthy eating and physical activity among Arab adolescents. METHOD:
A multistage stratified sampling method was used to select 4698 students aged 15
18 years (2240 males and 2458 females) from public schools. Seven Arab counties
were included in the study, namely, Algeria, Jordan, Kuwait, Libya, Palestine,
Syria, and the United Arab Emirates. Self-reported questionnaire was used to list
the barriers to healthy eating and physical activity facing these adolescents.
RESULTS: It was found that lack of information on healthy eating, lack of
motivation to eat a healthy diet, and not having time to prepare or eat healthy
food were the main barriers to healthy eating among both genders. For physical
activity, the main barriers selected were lack of motivation to do physical
activity, less support from teachers, and lack of time to do physical activity.
In general, females faced more barriers to physical activity than males in all
countries included. There were significant differences between males and females
within each country and among countries for most barriers. CONCLUSION:
Intervention programmes to combat obesity and other chronic noncommunicable
diseases in the Arab world should include solutions to overcome the barriers to
weight maintenance, particularly the sociocultural barriers to practising
physical activity.
PMID- 24348146
TI - Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.
AB - The combination of multiplemodules in parallel manner is an important way to
achieve the much higher thrust of scramjet engine. For the multiple-modules
scramjet engine, when inlet unstarted oscillatory flow appears in a single-module
engine due to high backpressure, how to interact with each module by massflow
spillage, and whether inlet unstart occurs in other modules are important issues.
The unstarted flowfield and coupling characteristic for a three-module hypersonic
inlet caused by center module II and side module III were, conducted
respectively. The results indicate that the other two hypersonic inlets are
forced into unstarted flow when unstarted phenomenon appears on a single-module
hypersonic inlet due to high backpressure, and the reversed flow in the isolator
dominates the formation, expansion, shrinkage, and disappearance of the vortexes,
and thus, it is the major factor of unstart coupling of multiple-modules
hypersonic inlet. The coupling effect among multiple modules makes hypersonic
inlet be more likely unstarted.
PMID- 24348147
TI - Thiol modification of psyllium husk mucilage and evaluation of its mucoadhesive
applications.
AB - Thiol functionalization of psyllium was carried out to enhance its mucoadhesive
potential. Thiolation of psyllium was achieved by esterification with
thioglycolic acid. Thiolation was observed to change the surface morphology of
psyllium from fibrous to granular and result in a slight increase in the
crystallinity and swelling. Thiolated psyllium was found to contain 3.282 m moles
of thiol groups/g of the polymer. Mucoadhesive applications of thiolated psylium
were explored by formulating gels using metronidazole as the model drug. On
comparative evaluation thiolated psyllium gels showed 3-fold higher mucoadhesive
strength than the psyllium gels as determined by modified physical balance using
chicken buccal pouch. The results of in vitro release study revealed that
thiolated psyllium gels provided a prolonged release of metronidazole. Further,
the psyllium and thiolated psyllium gels were found to release the drug following
first-order kinetics by combination of polymer relaxation and diffusion through
the matrix.
PMID- 24348148
TI - Exit, voice, and loyalty in the Italian public health service: macroeconomic and
corporate implications.
AB - The paper analyses how customers of public health organizations can express their
dissatisfaction for the services offered to them. The main aim is to evaluate the
effects that possible dissatisfaction of Italian public health service customers
can have on public health organizations. We adopted the methodological scheme
developed by Hirschman with exit, voice, and loyalty, considering the
macroeconomic and corporate implications that it causes for Italian public health
organizations. The study investigated the effects developed by exit of the
patients on the system of financing of local health authorities considering both
the corporate level of analysis and the macroeconomic level. As a result, local
health authority management is encouraged to pay greater attention to the exit
phenomena through the adoption of tools that promote loyalty, such as the
promotion of voice, even if exit is not promoting, at a macroeconomic level,
considerable attention to this phenomenon.
PMID- 24348149
TI - Review of inflammatory bowel disease in China.
AB - Inflammatory bowel disease mainly consisting of ulcerative colitis and Crohn's
disease has been rising gradually during the last two decades in China. In this
review article, we provide the latest epidemiological trends in incidence,
prevalence, and mortality of IBD patients in China and summarize the risk factors
and genetic susceptibility of Chinese IBD patients. We also compare these
characteristics to those of IBD patients in Western countries.
PMID- 24348150
TI - Overdiagnosis of bipolar disorder: a critical analysis of the literature.
AB - Bipolar disorder (BD) is considered one of the most disabling mental conditions,
with high rates of morbidity, disability, and premature death from suicide.
Although BD is often misdiagnosed as major depressive disorder, some attention
has recently been drawn to the possibility that BD could be overdiagnosed in some
settings. The present paper focuses on a critical analysis of the overdiagnosis
issue among bipolar patients. It includes a review of the available literature
findings, followed by some recommendations aiming at optimizing the diagnosis of
BD and increasing its reliability.
PMID- 24348151
TI - Some new generalized difference spaces of nonabsolute type derived from the
spaces l p and l infinity.
AB - We introduce the sequence space lplambda(B) of none absolute type which is a p
normed space and BK space in the cases 0[0, +infinity) is
continuous. Firstly, by constructing a special cone, applying Guo-Krasnoselskii's
fixed point theorem and Leggett-Williams fixed point theorem, some new existence
criteria for fractional boundary value problem are established; secondly, by
applying a new extension of Krasnoselskii's fixed point theorem, a sufficient
condition is obtained for the existence of multiple positive solutions to the
considered boundary value problem from its auxiliary problem. Finally, as
applications, some illustrative examples are presented to support the main
results.
PMID- 24348163
TI - Abatement of azo dye from wastewater using bimetal-chitosan.
AB - We introduce a new adsorbent, bimetallic chitosan particle (BCP) that is
successfully synthesized and applied to remove the orange II dye from wastewater.
The effects of pH, BCP quantity, and contact time are initially verified on the
basis of the percentage of orange II removed from the wastewater. Experimental
data reveal that the Cu/Mg bimetal and chitosan have a synergistic effect on the
adsorption process of the adsorbate, where the dye adsorption by Cu/Mg bimetal,
chitosan alone, and bimetal-chitosan is 10, 49, and 99.5%, respectively. The time
required for the complete decolorization of orange II by 1 mg/L of BCP is 10 min.
The Langmuir model is the best fit for the experimental data, which attains a
maximum adsorption capacity of 384.6 mg/g. The consideration of the kinetic
behavior indicates that the adsorption of orange II onto the BCP fits best with
the pseudo-second-order and Elovich models. Further, the simulated azo dye
wastewater can be effectively treated using a relatively low quantity of the
adsorbent, 1 mg/L, within a short reaction time of 20 min. Overall, the use of
BCP can be considered a promising method for eliminating the azo dye from
wastewater effectively.
PMID- 24348164
TI - Hands-off and hands-on casting consistency of amputee below knee sockets using
magnetic resonance imaging.
AB - Residual limb shape capturing (Casting) consistency has a great influence on the
quality of socket fit. Magnetic Resonance Imaging was used to establish a
reliable reference grid for intercast and intracast shape and volume consistency
of two common casting methods, Hands-off and Hands-on. Residual limbs were cast
for twelve people with a unilateral below knee amputation and scanned twice for
each casting concept. Subsequently, all four volume images of each amputee were
semiautomatically segmented and registered to a common coordinate system using
the tibia and then the shape and volume differences were calculated. The results
show that both casting methods have intra cast volume consistency and there is no
significant volume difference between the two methods. Inter- and intracast mean
volume differences were not clinically significant based on the volume of one
sock criteria. Neither the Hands-off nor the Hands-on method resulted in a
consistent residual limb shape as the coefficient of variation of shape
differences was high. The resultant shape of the residual limb in the Hands-off
casting was variable but the differences were not clinically significant. For the
Hands-on casting, shape differences were equal to the maximum acceptable limit
for a poor socket fit.
PMID- 24348165
TI - A location selection policy of live virtual machine migration for power saving
and load balancing.
AB - Green cloud data center has become a research hotspot of virtualized cloud
computing architecture. And load balancing has also been one of the most
important goals in cloud data centers. Since live virtual machine (VM) migration
technology is widely used and studied in cloud computing, we have focused on
location selection (migration policy) of live VM migration for power saving and
load balancing. We propose a novel approach MOGA-LS, which is a heuristic and
self-adaptive multiobjective optimization algorithm based on the improved genetic
algorithm (GA). This paper has presented the specific design and implementation
of MOGA-LS such as the design of the genetic operators, fitness values, and
elitism. We have introduced the Pareto dominance theory and the simulated
annealing (SA) idea into MOGA-LS and have presented the specific process to get
the final solution, and thus, the whole approach achieves a long-term efficient
optimization for power saving and load balancing. The experimental results
demonstrate that MOGA-LS evidently reduces the total incremental power
consumption and better protects the performance of VM migration and achieves the
balancing of system load compared with the existing research. It makes the result
of live VM migration more high-effective and meaningful.
PMID- 24348166
TI - Chemical, biochemical, and microbiological properties of soils from abandoned and
extensively cultivated olive orchards.
AB - The abandonment of olive orchards is a phenomenon of great importance triggered
mainly by economic and social causes. The aim of this study was to investigate
some chemical, biochemical, and microbiological properties in a soil of a
southern olive grove abandoned for 25 years. In order to define the effect of the
long-term land abandonment on soil properties, an adjacent olive grove managed
according to extensive practices was taken as reference (essentially minimum
tillage and no fertilization). Soil organic matter, total nitrogen, and pH were
significantly higher in the abandoned olive grove due to the absence of tillage
and the natural inputs of organic matter at high C/N ratio which, inter alia,
increased the number of cellulolytic bacteria and stimulated the activity of beta
-glucosidase, an indicator of a more advanced stage of soil evolution. The soil
of the abandoned olive orchard showed a lower number of total bacteria and fungi
and a lower microbial diversity, measured by means of the Biolog method, as a
result of a sort of specialization trend towards low quality organic substrates.
From this point of view, the extensive cultivation management seemed to not
induce a disturbance to microbiological communities.
PMID- 24348168
TI - Metal and precursor effect during 1-heptyne selective hydrogenation using an
activated carbon as support.
AB - Palladium, platinum, and ruthenium supported on activated carbon were used as
catalysts for the selective hydrogenation of 1-heptyne, a terminal alkyne. All
catalysts were characterized by temperature programmed reduction, X-ray
diffraction, transmission electron microscopy, and X-ray photoelectron
spectroscopy. TPR and XPS suggest that the metal in all catalysts is reduced
after the pretreatment with H2 at 673 K. The TPR trace of the PdNRX catalyst
shows that the support surface groups are greatly modified as a consequence of
the use of HNO3 during the catalyst preparation. During the hydrogenation of 1
heptyne, both palladium catalysts were more active and selective than the
platinum and ruthenium catalysts. The activity order of the catalysts is as
follows: PdClRX>PdNRX>PtClRX?RuClRX. This superior performance of PdClRX was
attributed in part to the total occupancy of the d electronic levels of the Pd
metal that is supposed to promote the rupture of the H2 bond during the
hydrogenation reaction. The activity differences between PdClRX and PdNRX
catalysts could be attributed to a better accessibility of the substrate to the
active sites, as a consequence of steric and electronic effects of the
superficial support groups. The order for the selectivity to 1-heptene is as
follows: PdClRX=PdNRX>RuClRX>PtClRX, and it can be mainly attributed to
thermodynamic effects.
PMID- 24348167
TI - Characterisation and in silico analysis of interleukin-4 cDNA of nilgai
(Boselaphus tragocamelus) and Indian buffalo (Bubalus bubalis).
AB - Interleukin-4 (IL-4) produced from Th2 cells modulates both innate and adaptive
immune responses. It is a common belief that wild animals possess better immunity
against diseases than domestic and laboratory animals; however, the immune system
of wild animals is not fully explored yet. Therefore, a comparative study was
designed to explore the wildlife immunity through characterisation of IL-4 cDNA
of nilgai, a wild ruminant, and Indian buffalo, a domestic ruminant. Total RNA
was extracted from peripheral blood mononuclear cells of nilgai and Indian
buffalo and reverse transcribed into cDNA. Respective cDNA was further cloned and
sequenced. Sequences were analysed in silico and compared with their homologues
available at GenBank. The deduced 135 amino acid protein of nilgai IL-4 is 95.6%
similar to that of Indian buffalo. N-linked glycosylation sequence, leader
sequence, Cysteine residues in the signal peptide region, and 3' UTR of IL-4 were
found to be conserved across species. Six nonsynonymous nucleotide substitutions
were found in Indian buffalo compared to nilgai amino acid sequence. Tertiary
structure of this protein in both species was modeled, and it was found that this
protein falls under 4-helical cytokines superfamily and short chain cytokine
family. Phylogenetic analysis revealed a single cluster of ruminants including
both nilgai and Indian buffalo that was placed distinct from other nonruminant
mammals.
PMID- 24348169
TI - Angular transmittance analysis of a novel thermotropic material.
AB - This paper uses inverse adding-doubling (IAD) method and Monte Carlo method for
the simulation of the spectral angular transmittance of a novel kind of
thermotropic material at different temperatures. The results show that the
collimated light takes the major part at the beginning of the switching process
and the scattered light is negligible. However, the scattered light increased to
high above 80% of the total transmitted light with the largest angle distribution
of scattered light about 30 degrees as temperature elevated.
PMID- 24348170
TI - Laboratory diagnosis of human rabies: recent advances.
AB - Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly
through the bite of a rabid animal, is responsible for an estimated 61,000 human
deaths worldwide. The true disease burden and public health impact due to rabies
remain underestimated due to lack of sensitive laboratory diagnostic methods.
Rapid diagnosis of rabies can help initiate prompt infection control and public
health measures, obviate the need for unnecessary treatment/medical tests, and
assist in timely administration of pre- or postexposure prophylactic vaccination
to family members and medical staff. Antemortem diagnosis of human rabies
provides an impetus for clinicians to attempt experimental therapeutic approaches
in some patients, especially after the reported survival of a few cases of human
rabies. Traditional methods for antemortem and postmortem rabies diagnosis have
several limitations. Recent advances in technology have led to the improvement or
development of several diagnostic assays which include methods for rabies viral
antigen and antibody detection and assays for viral nucleic acid detection and
identification of specific biomarkers. These assays which complement traditional
methods have the potential to revolutionize rabies diagnosis in future.
PMID- 24348172
TI - Preliminary computational hemodynamics study of double aortic aneurysms under
multistage surgical procedures: an idealised model study.
AB - Double aortic aneurysm (DAA) falls under the category of multiple aortic
aneurysms. Repair is generally done through staged surgery due to low
invasiveness. In this approach, one aneurysm is cured per operation. Therefore,
two operations are required for DAA. However, post-first-surgery rupture cases
have been reported. Although the problems involved with managing staged surgery
have been discussed for more than 30 years, investigation from a hemodynamic
perspective has not been attempted. Hence, this is the first computational fluid
dynamics approach to the DAA problem. Three idealized geometries were prepared:
presurgery, thoracic aortic aneurysm (TAA) cured, and abdominal aortic aneurysm
(AAA) cured. By applying identical boundary conditions for flow rate and
pressure, the Navier-Stokes equation and continuity equations were solved under
the Newtonian fluid assumption. Average pressure in TAA was increased by AAA
repair. On the other hand, average pressure in AAA was decreased after TAA
repair. Average wall shear stress was decreased at the peak in post-first-surgery
models. However, the wave profile of TAA average wall shear stress was changed in
the late systole phase after AAA repair. Since the average wall shear stress in
the post-first-surgery models decreased and pressure at TAA after AAA repair
increased, the TAA might be treated first to prevent rupture.
PMID- 24348171
TI - Emerging paradigms in genomics-based crop improvement.
AB - Next generation sequencing platforms and high-throughput genotyping assays have
remarkably expedited the pace of development of genomic tools and resources for
several crops. Complementing the technological developments, conceptual shifts
have also been witnessed in designing experimental populations. Availability of
second generation mapping populations encompassing multiple alleles, multiple
traits, and extensive recombination events is radically changing the phenomenon
of classical QTL mapping. Additionally, the rising molecular breeding approaches
like marker assisted recurrent selection (MARS) that are able to harness several
QTLs are of particular importance in obtaining a "designed" genotype carrying the
most desirable combinations of favourable alleles. Furthermore, rapid generation
of genome-wide marker data coupled with easy access to precise and accurate
phenotypic screens enable large-scale exploitation of LD not only to discover
novel QTLs via whole genome association scans but also to practise genomic
estimated breeding value (GEBV)-based selection of genotypes. Given refinements
being experienced in analytical methods and software tools, the multiparent
populations will be the resource of choice to undertake genome wide association
studies (GWAS), multiparent MARS, and genomic selection (GS). With this, it is
envisioned that these high-throughput and high-power molecular breeding methods
would greatly assist in exploiting the enormous potential underlying breeding by
design approach to facilitate accelerated crop improvement.
PMID- 24348173
TI - Evaluation of in vitro antioxidant properties of methanol and aqueous extracts of
Parkinsonia aculeata L. leaves.
AB - In the present study, methanol and aqueous extracts of Parkinsonia aculeata L.
leaves were prepared and analyzed for phytochemical analysis and antioxidant
potential in different in vitro assays. Antioxidant activity was studied using
DPPH, CUPRAC, reducing power assay, deoxyribose degradation (site and nonsite
specific), ferric reducing antioxidant potential (FRAP), ferric thiocyanate
(FTC), thiobarbituric acid (TBA), and molybdate ion reduction, respectively. The
total phenolic contents of the methanol and aqueous leaf extract were 39 mg GAE/g
and 38 mg GAE/g, whereas flavonoid contents of these extracts were found to be
0.013 mg RE/g and 0.006 mg RE/g, respectively. From the two extracts, the
methanol extract shows maximum inhibition (%) of 57.82%, 71.23%, 48.26%, 69.85%,
and 52.78% in DPPH, nonsite- and site-specific, FTC, and TBA assays and
absorbance of 0.669 and 0.241 in reducing power and CUPRAC assays at the highest
concentration tested. UPLC analysis was done to determine the presence of various
types of polyphenols present in plant extracts.
PMID- 24348174
TI - Insights on the phytochemical profile (cyclopeptides) and biological activities
of Calotropis procera latex organic fractions.
AB - Calotropis procera is a medicinal plant whose pharmacological properties are
associated with its latex. Here, the Calotropis procera latex fractions were
investigated in an attempt to trace its phytochemical profile and measure its
anti-inflammatory and toxicity activity. The crude latex was partitioned,
yielding five fractions (49.4% hexane, 5.2% dichloromethane, 2.0% ethyl acetate,
2.1% n-butanol, and 41.1% aqueous). Phytochemical screening and spectroscopy
analysis revealed that dichloromethane is the most chemically diverse fraction.
Triterpenes were detected in both the hexane and dichloromethane fractions, while
flavonoids were detected in the dichloromethane and ethyl acetate fractions.
These fractions were cytotoxic to cancer cell lines (LD50 0.05 to 3.9 MU g/mL)
and lethal to brine shrimp (LD50 10.9 to 65.7 MU g/mL). Reduced neutrophil
migration in rats was observed in carrageenan-induced peritonitis for the
dichloromethane (67%), ethyl acetate (56%), and aqueous (72%) fractions. A
positive reaction with tolidine and ninhydrin suggested that cyclopeptides are in
the ethyl acetate fraction. It is therefore concluded that Calotropis procera
latex dichloromethane and ethyl acetate fractions exhibit both in vitro and in
vivo activities as well as anti-inflammatory properties. Cyclopeptide detection
is especially interesting because previous attempts to investigate these low
molecular cyclic amino acid sequences in C. procera have failed.
PMID- 24348175
TI - Studying the relationship between robustness against mutations in metabolic
networks and lifestyle of organisms.
AB - Robustness is the key feature of biological networks that enables living
organisms to keep their homeostatic state and to survive against external and
internal perturbations. Variations in environmental conditions or nutrients and
intracellular changes such as genetic mutations have the potential to change
stability and efficiency of an organism. Structural robustness helps biological
systems to choose alternative routes of adaptation to varying conditions. In this
study, in order to estimate the structural robustness in metabolic networks we
presented a novel flux balance-based approach inspired by bond percolation
theory. Fourteen in silico metabolic models were studied in this work in order to
examine the possible relationship between the lifestyle of organisms and their
metabolic robustness. The results of this study confirm that in organisms which
are highly adapted to their environment robustness to mutations may decrease
compared to other organisms.
PMID- 24348176
TI - Effect of supplementation with antioxidants on the quality of bovine milk and
meat production.
AB - From a clinical point of view, oxidative stress (OS) is considered the primary
cause of numerous metabolic processes in transition cow. Thus, the addition of
antioxidants has been considered a palliative or preventive treatment. But beyond
the clinical perspective, antioxidant supplementation provides an added value to
the product obtained being either milk or meat. This paper reviews the beneficial
aspects that provide antioxidant supplementation on quality of both products and
that fit into the new concept that the consumer has a functional and healthy
food. Our approach is from a veterinary standpoint, by reviewing the studies
conducted to date and the new perspectives that are interesting and need to be
studied in the following years. One of the highlights is that sustainable
farming, one in which production is combined with animal health, also impacts
positively on the quality of the final products, with beneficial antioxidant
properties to human health.
PMID- 24348177
TI - Application of three-dimensional imaging to the intestinal crypt organoids and
biopsied intestinal tissues.
AB - Two-dimensional (2D) histopathology is the standard analytical method for
intestinal biopsied tissues; however, the role of 3-dimensional (3D) imaging
system in the analysis of the intestinal tissues is unclear. The 3D structure of
the crypt organoids from the intestinal stem cell culture and intestinal tissues
from the donors and recipients after intestinal transplantation was observed
using a 3D imaging system and compared with 2D histopathology and
immunohistochemistry. The crypt organoids and intestinal tissues showed well
defined 3D structures. The 3D images of the intestinal tissues with acute
rejection revealed absence of villi and few crypts, which were consistent with
the histopathological features. In the intestinal transplant for megacystis
microcolon intestinal hypoperistalsis syndrome, the donor's intestinal tissues
had well-developed nerve networks and interstitial cells of Cajal (ICCs) in the
muscle layer, while the recipient's intestinal tissues had distorted nerve
network and the ICCs were few and sparsely distributed, relative to those of the
donor. The 3D images showed a clear spatial relationship between the
microstructures of the small bowel and the features of graft rejection. In
conclusion, integration of the 3D imaging and 2D histopathology provided a global
view of the intestinal tissues from the transplant patients.
PMID- 24348178
TI - PLZF expression during colorectal cancer development and in normal colorectal
mucosa according to body size, as marker of colorectal cancer risk.
AB - Promyelocytic leukemia zinc finger protein (PLZF) is a protein involved in
various signaling, growth regulatory, and differentiation pathways, including
development/function of some T cells. Here, we aimed at the detection of PLZF
during colorectal carcinogenesis, using immunofluorescence, and at the evaluation
of the colocalization of PLZF with CD2 and CD56 positive cells (T, gamma delta ,
NK, and NKT cells), using confocal-microscopy, along colorectal carcinogenesis,
since its earliest stages, that is, dysplastic aberrant crypt foci (ACF).
Furthermore, we analyzed PLZF in the normal colonic mucosa (NM) according to
anthropometric parameters of the subject. NM exhibited strong CD56 fluorescent
staining. This infiltration was lost in both ACF and colorectal carcinoma (CRC),
while PLZF presence increased from NM to ACF and CRC. Strong association was
found between CD56+ colonic mucosa cell infiltration and body mass index.
Interestingly, an increased stromal PLZF-reactivity was present in NM of obese
subjects. This study shows that overexpression of PLZF and exclusion of NK cells
in dysplastic microenvironment are very early events in the stepwise sequence
leading to CRC and that lower levels of CD56+ cells in NM, together with
increased levels of PLZF+ cells, can be a reflection of colon cancer risk due to
obesity.
PMID- 24348179
TI - Ultrasound for the anesthesiologists: present and future.
AB - Ultrasound is a safe, portable, relatively inexpensive, and easily accessible
imaging modality, making it a useful diagnostic and monitoring tool in medicine.
Anesthesiologists encounter a variety of emergent situations and may benefit from
the application of such a rapid and accurate diagnostic tool in their routine
practice. This paper reviews current and potential applications of ultrasound in
anesthesiology in order to encourage anesthesiologists to learn and use this
useful tool as an adjunct to physical examination. Ultrasound-guided peripheral
nerve blockade and vascular access represent the most popular ultrasound
applications in anesthesiology. Ultrasound has recently started to substitute for
CT scans and fluoroscopy in many pain treatment procedures. Although the
application of airway ultrasound is still limited, it has a promising future.
Lung ultrasound is a well-established field in point-of-care medicine, and it
could have a great impact if utilized in our ORs, as it may help in rapid and
accurate diagnosis in many emergent situations. Optic nerve sheath diameter
(ONSD) measurement and transcranial color coded duplex (TCCD) are relatively new
neuroimaging modalities, which assess intracranial pressure and cerebral blood
flow. Gastric ultrasound can be used for assessment of gastric content and
diagnosis of full stomach. Focused transthoracic (TTE) and transesophageal (TEE)
echocardiography facilitate the assessment of left and right ventricular
function, cardiac valve abnormalities, and volume status as well as guiding
cardiac resuscitation. Thus, there are multiple potential areas where ultrasound
can play a significant role in guiding otherwise blind and invasive
interventions, diagnosing critical conditions, and assessing for possible
anatomic variations that may lead to plan modification. We suggest that
ultrasound training should be part of any anesthesiology training program
curriculum.
PMID- 24348181
TI - Cure kinetics of epoxy nanocomposites affected by MWCNTs functionalization: a
review.
AB - The current paper provides an overview to emphasize the role of functionalization
of multiwalled carbon nanotubes (MWCNTs) in manipulating cure kinetics of epoxy
nanocomposites, which itself determines ultimate properties of the resulting
compound. In this regard, the most commonly used functionalization schemes, that
is, carboxylation and amidation, are thoroughly surveyed to highlight the role of
functionalized nanotubes in controlling the rate of autocatalytic and
vitrification kinetics. The current literature elucidates that the mechanism of
curing in epoxy/MWCNTs nanocomposites remains almost unaffected by the
functionalization of carbon nanotubes. On the other hand, early stage
facilitation of autocatalytic reactions in the presence of MWCNTs bearing amine
groups has been addressed by several researchers. When carboxylated nanotubes
were used to modify MWCNTs, the rate of such reactions diminished as a
consequence of heterogeneous dispersion within the epoxy matrix. At later stages
of curing, however, the prolonged vitrification was seen to be dominant. Thus,
the type of functional groups covalently located on the surface of MWCNTs
directly affects the degree of polymer-nanotube interaction followed by
enhancement of curing reaction. Our survey demonstrated that most widespread
efforts ever made to represent multifarious surface-treated MWCNTs have not been
directed towards preparation of epoxy nanocomposites, but they could result in
property synergism.
PMID- 24348180
TI - The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) reduces
urinary bladder damage during cyclophosphamide-induced cystitis in rats.
AB - Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy,
which deserves new therapeutic strategies, such as those based on natural
products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.)
(EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities
as previously showed by our group. We have investigated the effect of EECp on the
cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the
injection of cyclophosphamide. These animals were pretreated with EECp (100-400
mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation
were measured in urinary bladder and other tissues. Bladder edema and
histopathological alterations and serum nitric oxide metabolites concentration
NOx- were also evaluated. Treatment with EECp (100-400 mg/kg) or mesna impaired
the increase of myeloperoxidase activity in urinary bladder and the serum NOx-
induced by cyclophosphamide but did not reduce edema in this tissue, as did
mesna. Total histological score was reduced by EECp (100 mg/kg). Lung
myeloperoxidase activity, which was increased by cyclophosphamide, was decreased
significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde
formation in bladder, lung, and spleen, although these parameters were not
affected by cyclophosphamide. These results indicate that EECp reduced urinary
bladder damage during cyclophosphamide-induced HC in rats.
PMID- 24348182
TI - Characterization of human colorectal cancer MDR1/P-gp Fab antibody.
AB - In this study, the peptide sized 21 kDa covering P-gp transmembrane region was
first prepared for generating a novel mouse monoclonal antibody Fab fragment with
biological activity against multiple drug resistance protein P-gp21 by phage
display technology. Phage-displayed antibody library prepared from mice spleen
tissues was selected against the recombinant protein P-gp21 with five rounds of
panning. A number of clones expressing Fab bound to P-gp21, showing neutralized
activity in vitro, were isolated and screened by enzyme-linked immunosorbent
assay based on its recognition properties to P-gp21 and human colorectal cancer
tissue homogenate, resulting in identification of an optimal recombinant Fab
clone (Number 29). Further characterization by recloning number 29 into an
expression vector showed significant induction of the Fab antibody in the clone
number 29 by Isopropyl beta-D-1-thiogalactopyranoside (IPTG). After purified by
HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also
confirmed. Not only was the targeted region of this monoclonal Fab antibody
identified as a 16-peptide epitope (ALKDKKELEGSGKIAT) comprising residues 883-898
within the transmembrane (TM) domain of human P-gp, but also the binding ability
with it was verified. The clinical implication of our results for development of
personalized therapy of colorectal cancer will be further studied.
PMID- 24348183
TI - Characterization of thermo- and detergent stable antigenic glycosylated cysteine
protease of Euphorbia nivulia Buch.-Ham. and evaluation of its ecofriendly
applications.
AB - An antigenic glycosylated cysteine protease has been purified from the latex of
Euphorbia nivulia Buch.-Ham. It exhibits remarkable protease activity in the
presence of metal ions, oxidizing agents, organic solvents, and detergents. This
enzyme showed potential role in leather processing industry due to its dehairing
activity for animal hide without hydrolyzing fibrous proteins, producing, by this
way, a better quality product. The enzyme can also be used for silver recovering
from X-ray plates. In addition, the stability (temperature and surfactants) and
hydrolysis of blood stain data also revealed its application in detergent
industries. Agriculturally, this protease finds application in biocontrol process
against the infectious management of root knot nematode, Meloidogyne incognita.
Biologically, it shows noticeable wound healing, haemostatic and antibacterial
activity.
PMID- 24348184
TI - Predictors of delayed entry into medical care of children diagnosed with HIV
infection: data from an HIV cohort study in India.
AB - Data about the attrition before entry into care of children diagnosed with HIV in
low- or middle-income countries are scarce. The aim of this study is to describe
the attrition before engagement in HIV medical care in 523 children who were
diagnosed with HIV from 2007 to 2012 in a cohort study in India. The cumulative
incidence of children who entered into care was 87.2% at one year, but most
children who did not enter into care within one year were lost to followup. The
mortality before entry into care was low (1.3% at one year) and concentrated
during the first three months after HIV diagnosis. Factors associated with
delayed entry into care were being diagnosed after mother's HIV diagnosis,
belonging to scheduled castes, age<18 months, female gender, and living >90
minutes from the HIV centre. Children whose parents were alive and were living in
a rented house were at a higher risk of delayed entry into care than those who
were living in an owned house. The results of this study can be used to improve
the linkage between HIV testing and HIV care of children diagnosed with HIV in
India.
PMID- 24348186
TI - A fast algorithm for computing binomial coefficients modulo powers of two.
AB - I present a new algorithm for computing binomial coefficients modulo 2N. The
proposed method has an O(N3.Multiplication(N)+N4) preprocessing time, after which
a binomial coefficient C(P, Q) with 0<=Q<=P<=2N-1 can be computed modulo 2N in
O(N2.log(N).Multiplication(N)) time. Multiplication(N) denotes the time
complexity of multiplying two N-bit numbers, which can range from O(N2) to
O(N.log(N).log(log(N))) or better. Thus, the overall time complexity for
evaluating M binomial coefficients C(P, Q) modulo 2N with 0<=Q<=P<=2N-1 is
O((N3+M.N2.log(N)).Multiplication(N)+N4). After preprocessing, we can actually
compute binomial coefficients modulo any 2R with R<=N. For larger values of P and
Q, variations of Lucas' theorem must be used first in order to reduce the
computation to the evaluation of multiple (O(log(P))) binomial coefficients C(P',
Q') (or restricted types of factorials P'!) modulo 2N with 0<=Q'<=P'<=2N-1.
PMID- 24348187
TI - Strong convergence of a monotone projection algorithm in a Banach space.
AB - In this paper, a common solution problem is investigated based on a Bregman
projection. Strong convergence of the monotone projection algorithm for monotone
operators and bifunctions is obtained in a reflexive Banach space.
PMID- 24348185
TI - Islet-1 immunoreactivity in the developing retina of Xenopus laevis.
AB - The LIM-homeodomain transcription factor Islet1 (Isl1) has been widely used as a
marker of neuronal differentiation in the developing visual system of different
classes of vertebrates, including mammals, birds, reptiles, and fish. In the
present study, we analyzed the spatial and temporal distribution of Isl1
immunoreactive cells during Xenopus laevis retinal development and its relation
to the formation of the retinal layers, and in combination with different markers
of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the
cell nuclei of sparse differentiating neuroblasts located in the vitreal surface
of the undifferentiated retina. At St35-36, abundant Isl1-positive cells
accumulated at the vitreal surface of the neuroepithelium. As development
proceeded and through the postmetamorphic juveniles, Isl1 expression was
identified in subpopulations of ganglion cells and in subsets of amacrine,
bipolar, and horizontal cells. These data together suggest a possible role for
Isl1 in the early differentiation and maintenance of different retinal cell
types, and Isl1 can serve as a specific molecular marker for the study of retinal
cell specification in X. laevis.
PMID- 24348188
TI - On the relationship between multicast/broadcast throughput and resource
utilizations in wireless mesh networks.
AB - This paper deals with the problem of multicast/broadcast throughput in multi
channel multi-radio wireless mesh networks that suffer from the resource
constraints. We provide a formulation to capture the utilization of the network
resources and derive analytical relationships for the network's throughput in
terms of the node utilization, the channel utilization, and the number of
transmissions. Our model relies on the on-demand quality of service
multicast/broadcast sessions, where each admitted session creates a unique tree
with a specific bandwidth. As an advantage, the derived relationships are
independent of the type of tree built for each session and can be used for
different protocols. The proposed formulation considers the channel assignment
strategy and reflects both the wireless broadcast advantage and the interference
constraint. We also offer a comprehensive discussion to evaluate the effects of
load-balancing and number of transmissions on the network's throughput. Numerical
results confirm the accuracy of the presented analysis.
PMID- 24348189
TI - Water plasma functionalized CNTs/MnO2 composites for supercapacitors.
AB - A water plasma treatment applied to vertically-aligned multiwall carbon nanotubes
(CNTs) synthesized by plasma enhanced chemical vapour deposition gives rise to
surface functionalization and purification of the CNTs, along with an improvement
of their electrochemical properties. Additional increase of their charge storage
capability is achieved by anodic deposition of manganese dioxide lining the
surface of plasma-treated nanotubes. The morphology (nanoflower, layer, or needle
like structure) and oxidation state of manganese oxide depend on the voltage
window applied during charge-discharge measurements and are found to be key
points for improved efficiency of capacitor devices. MnO2/CNTs nanocomposites
exhibit an increase in their specific capacitance from 678 Fg(-1), for untreated
CNTs, up to 750 Fg(-1), for water plasma-treated CNTs.
PMID- 24348191
TI - Analytical analysis of motion separability.
AB - Motion segmentation is an important task in computer vision and several practical
approaches have already been developed. A common approach to motion segmentation
is to use the optical flow and formulate the segmentation problem using a linear
approximation of the brightness constancy constraints. Although there are
numerous solutions to solve this problem and their accuracies and reliabilities
have been studied, the exact definition of the segmentation problem, its
theoretical feasibility and the conditions for successful motion segmentation are
yet to be derived. This paper presents a simplified theoretical framework for the
prediction of feasibility, of segmentation of a two-dimensional linear equation
system. A statistical definition of a separable motion (structure) is presented
and a relatively straightforward criterion for predicting the separability of two
different motions in this framework is derived. The applicability of the proposed
criterion for prediction of the existence of multiple motions in practice is
examined using both synthetic and real image sequences. The prescribed
separability criterion is useful in designing computer vision applications as it
is solely based on the amount of relative motion and the scale of measurement
noise.
PMID- 24348190
TI - Phenotypes and genotypes of patients with pantothenate kinase-associated
neurodegeneration in Asian and Caucasian populations: 2 cases and literature
review.
AB - OBJECTIVES: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare
disease caused by pantothenate kinase 2 (PANK2, OMIM 606157) mutations. This
study is aimed to investigate clinical presentations, pathologies, and genetics
in patients with PKAN. METHODS: Two patients with PKAN were reported. We reviewed
the literature to include additional 19 patients with PKAN in Eastern Asia. These
patients were divided into classic and atypical groups by the age of onset. We
compared the data on PKAN patients of Asian and Caucasian populations. RESULTS:
We found iron deposits in the globus pallidus in our Patient 1 and a heterozygous
truncating mutation (c.1408insT) in Patient 2. Literature review shows that
generalized dystonia and bulbar signs are more common in classic PKAN patients,
whereas segmental dystonia and tremors are more specific to atypical ones. Asian
patients have less complex presentations--lower prevalence of pyramidal signs,
mental impairment, and parkinsonism--than Caucasians. D378G in exon 3 is the most
frequent mutation (28%) in Asians. CONCLUSIONS: Our study demonstrates that the
distribution of dystonia is the major distinction between subgroups of PKAN.
Caucasian patients have more complex presentations than Asians. Exon 3 and 4 are
hot spots for screening PANK2 mutations in Asian patients.
PMID- 24348192
TI - Air temperature change in the southern Tarim River Basin, China, 1964-2011.
AB - The temperature data from 3 meteorological stations (Kashi, Ruoqiang, and Hotan)
in the South of Tarim River Basin (STRB) during 1964-2011 were analyzed by Mann
Kendall test and correlation analysis. The results from Mann-Kendall test show
that the surface temperature (ST), 850 hPa temperature (T850), and 700 hPa
temperature (T700) exhibited upward trends, while 300 hPa temperature (T300)
revealed a downward trend. On the whole, the change rate of ST, T850, T700, and
T300 was 0.26~0.46 degrees C/10a, 0.15~0.40 degrees C/10a, 0.03~0.10 degrees
C/10a, and -0.38~-0.13 degrees C/10a, respectively. For the periods, ST and T850
declined during 1964-1997 and then rose during 1998-2011. T700 declined during
1964-2005 and then rose during 2006-2011, while T300 rose from 1964 to 1970s and
then declined. The results from correlation analysis show that T850 and T700
positively correlated with ST (P<0.01) at the all three stations and there was a
negative correlation between T300 and ST at Hotan (P<0.1), while the correlation
is not significant at Kashi and Ruoqiang. The results indicate that there were
gradient differences in the response of upper-air temperature (UT) to ST change.
PMID- 24348194
TI - Fabrication of flexible piezoelectric PZT/fabric composite.
AB - Flexible piezoelectric PZT/fabric composite material is pliable and tough in
nature which is in a lack of traditional PZT patches. It has great application
prospect in improving the sensitivity of sensor/actuator made by piezoelectric
materials especially when they are used for curved surfaces or complicated
conditions. In this paper, glass fiber cloth was adopted as carrier to grow PZT
piezoelectric crystal particles by hydrothermal method, and the optimum
conditions were studied. The results showed that the soft glass fiber cloth was
an ideal kind of carrier. A large number of cubic-shaped PZT nanocrystallines
grew firmly in the carrier with a dense and uniform distribution. The best
hydrothermal condition was found to be pH 13, reaction time 24 h, and reaction
temperature 200 degrees C.
PMID- 24348195
TI - Donor-like surface traps on two-dimensional electron gas and current collapse of
AlGaN/GaN HEMTs.
AB - The effect of donor-like surface traps on two-dimensional electron gas (2DEG) and
drain current collapse of AlGaN/GaN high electron mobility transistors (HEMTs)
has been investigated in detail. The depletion of 2DEG by the donor-like surface
states is shown. The drain current collapse is found to be more sensitive to the
addition of positive surface charges. Surface trap states with higher energy
levels result in weaker current collapse and faster collapse process. By adopting
an optimized backside doping scheme, the electron density of 2DEG has been
improved greatly and the current collapse has been greatly eliminated. These
results give reference to the improvement in device performance of AlGaN/GaN
HEMTs.
PMID- 24348196
TI - Preparation of soft magnetic Fe-Ni-Pb-B alloy nanoparticles by room temperature
solid-solid reaction.
AB - The Fe-Ni-Pb-B alloy nanoparticles was prepared by a solid-solid chemical
reaction of ferric trichloride, nickel chloride, lead acetate, and potassium
borohydride powders at room temperature. The research results of the ICP and
thermal analysis indicate that the resultants are composed of iron, nickel, lead,
boron, and PVP, and the component of the alloy is connected with the mole ratio
of potassium borohydride and the metal salts. The TEM images show that the
resultants are ultrafine and spherical particles, and the particle size is about
a diameter of 25 nm. The largest saturation magnetization value of the 21.18 emu
g(-1) is obtained in the Fe-Ni-Pb-B alloy. The mechanism of the preparation
reaction for the Fe-Ni-Pb-B multicomponent alloys is discussed.
PMID- 24348193
TI - Pharmacological effects of active compounds on neurodegenerative disease with
gastrodia and uncaria decoction, a commonly used poststroke decoction.
AB - Neurodegenerative diseases refer to the selective loss of neuronal systems in
patients. The diseases cause high morbidity and mortality to approximately 22
million people worldwide and the number is expected to be tripled by 2050. Up to
now, there is no effective prevention and treatment for the neurodegenerative
diseases. Although some of the clinical therapies target at slowing down the
progression of symptoms of the diseases, the general effectiveness of the drugs
has been far from satisfactory. Traditional Chinese medicine becomes popular
alternative remedies as it has been practiced clinically for more than thousands
of years in China. As neurodegenerative diseases are mediated through different
pathways, herbal decoction with multiple herbs is used as an effective
therapeutic approach to work on multiple targets. Gastrodia and Uncaria
Decoction, a popular TCM decoction, has been used to treat stroke in China. The
decoction contains compounds including alkaloids, flavonoids, iridoids,
carotenoids, and natural phenols, which have been found to possess anti
inflammatory, antioxidative, and antiapoptotic effects. In this review, we will
summarize the recent publications of the pharmacological effects of these five
groups of compounds. Understanding the mechanisms of action of these compounds
may provide new treatment opportunities for the patients with neurodegenerative
diseases.
PMID- 24348197
TI - Some endpoint results for beta-generalized weak contractive multifunctions.
AB - We introduce beta-generalized weak contractive multifunctions and give some
results about endpoints of the multifunctions. Also, we give some results about
role of a point in the existence of endpoints.
PMID- 24348198
TI - Feature-based classification of amino acid substitutions outside conserved
functional protein domains.
AB - There are more than 500 amino acid substitutions in each human genome, and
bioinformatics tools irreplaceably contribute to determination of their
functional effects. We have developed feature-based algorithm for the detection
of mutations outside conserved functional domains (CFDs) and compared its
classification efficacy with the most commonly used phylogeny-based tools,
PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum
method (ISM), a feature-based technique, and statistical analysis. Our dataset
contained neutral polymorphisms and mutations associated with myeloid
malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2
and SIFT had significantly lower accuracies in predicting the effects of amino
acid substitutions outside CFDs than expected, with especially low sensitivity.
On the other hand, only ISM algorithm showed statistically significant
classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and
13%, respectively. These results suggest that feature-based methods, like ISM,
are more suitable for the classification of amino acid substitutions outside CFDs
than phylogeny-based tools.
PMID- 24348199
TI - Rural Poverty Dynamics and Refugee Communities in South Africa: A Spatial
Temporal Model.
AB - The assimilation of refugees into their host community economic structures is
often problematic. The paper investigates the ability of refugees in rural South
Africa to accumulate assets over time relative to their host community. Bayesian
spatial-temporal modelling was employed to analyse a longitudinal database that
indicated that the asset accumulation rate of former Mozambican refugee
households was similar to their host community; however, they were unable to
close the wealth gap. A series of geo-statistical wealth maps illustrate that
there is a spatial element to the higher levels of absolute poverty in the former
refugee villages. The primary reason for this is their physical location in drier
conditions that are established further away from facilities and infrastructure.
Neighbouring South African villages in close proximity, however, display lower
levels of absolute poverty, suggesting that the spatial location of the refugees
only partially explains their disadvantaged situation. In this regard, the
results indicate that the wealth of former refugee households continues to be
more compromised by higher mortality levels, poorer education, and less access to
high-return employment opportunities. The long-term impact of low initial asset
status appears to be perpetuated in this instance by difficulties in obtaining
legal status in order to access state pensions, facilities, and opportunities.
The usefulness of the results is that they can be used to sharpen the targeting
of differentiated policy in a given geographical area for refugee communities in
rural Africa. Copyright (c) 2011 John Wiley & Sons, Ltd.
PMID- 24348201
TI - No question about exciting questions in cell biology.
AB - Although we have a good grasp of many important processes in cell biology,
including knowledge of many molecules involved and how they interact with each
other, we still do not understand most of the dynamical features that are the
essence of living systems. Fortunately, we now have the ability to dissect
biological systems in enough detail to understand their dynamics, including the
use of mathematical models to account for past observations and predict future
experiments. This deep level of mechanistic understanding should be our goal-not
simply to satisfy our scientific curiosity, but also to understand the causes of
disease well enough to predict risks, make early diagnoses, and treat
effectively. Many big questions remain to be answered before we reach this goal
of understanding cellular dynamics.
PMID- 24348200
TI - Translational profiling of clock cells reveals circadianly synchronized protein
synthesis.
AB - Genome-wide studies of circadian transcription or mRNA translation have been
hindered by the presence of heterogeneous cell populations in complex tissues
such as the nervous system. We describe here the use of a Drosophila cell
specific translational profiling approach to document the rhythmic "translatome"
of neural clock cells for the first time in any organism. Unexpectedly,
translation of most clock-regulated transcripts--as assayed by mRNA ribosome
association--occurs at one of two predominant circadian phases, midday or mid
night, times of behavioral quiescence; mRNAs encoding similar cellular functions
are translated at the same time of day. Our analysis also indicates that
fundamental cellular processes--metabolism, energy production, redox state (e.g.,
the thioredoxin system), cell growth, signaling and others--are rhythmically
modulated within clock cells via synchronized protein synthesis. Our approach is
validated by the identification of mRNAs known to exhibit circadian changes in
abundance and the discovery of hundreds of novel mRNAs that show translational
rhythms. This includes Tdc2, encoding a neurotransmitter synthetic enzyme, which
we demonstrate is required within clock neurons for normal circadian locomotor
activity.
PMID- 24348202
TI - Addressing Trauma Among Women With Serious Addictive Disorders: Treatment Models,
Program Factors, And Potential Mediators.
AB - A large majority of women entering addiction treatment present significant
symptoms of trauma related to physical or sexual abuse. Despite research
indicating that trauma interventions are integral to women's successful recovery
from addiction, many programs do not adequately address violence-related trauma.
This chapter provides a review of the literature on trauma among women with
addictive disorders and several manual based interventions developed to address
co-occurring addiction and trauma-related disorders. One intervention, "Beyond
Trauma," which has become increasingly popular among community based programs is
described in detail. Beyond Trauma appears to have several advantages over other
therapies for treating trauma and addiction in women, including 1) a theoretical
foundation that draws on relational theory as a guide to the intervention, 2) a
broad based approach that can be utilized by a variety of professional and
paraprofessional staff members, 3) a focus that goes beyond treating women with a
formal diagnosis of post traumatic stress disorder to include treatment for an
array of symptoms and problems associated with trauma, and 4) gender-appropriate
use of expressive arts in its curriculum. The chapter also discusses treatment
program environment factors that may be critically important to treatment outcome
for women: 1) whether the program is gender specific, 2) the degree of emphasis
on peer involvement in recovery, 3) program recognition of the value of knowledge
based recovery experience, 4) program facilitation of cohesion, 5) the
empowerment of clients in decisions affecting the program and 6) skills training
relevant to managing moods, relationships and a variety of problems that women
face during recovery. Possible mechanisms of change for Beyond Trauma are
explored with particular emphasis on the variety of ways the intervention
attempts to impact problem areas experienced by women (e.g., mental health
functioning self esteem and social support). Recommendations for future research
in the treatment of trauma and addiction-related disorders in women are outlined.
PMID- 24348204
TI - Artemisinin combination therapy: a good antimalarial, but is the dose right?
PMID- 24348203
TI - Characterization of regional influenza seasonality patterns in China and
implications for vaccination strategies: spatio-temporal modeling of surveillance
data.
AB - BACKGROUND: The complexity of influenza seasonal patterns in the inter-tropical
zone impedes the establishment of effective routine immunization programs. China
is a climatologically and economically diverse country, which has yet to
establish a national influenza vaccination program. Here we characterize the
diversity of influenza seasonality in China and make recommendations to guide
future vaccination programs. METHODS AND FINDINGS: We compiled weekly reports of
laboratory-confirmed influenza A and B infections from sentinel hospitals in
cities representing 30 Chinese provinces, 2005-2011, and data on population
demographics, mobility patterns, socio-economic, and climate factors. We applied
linear regression models with harmonic terms to estimate influenza seasonal
characteristics, including the amplitude of annual and semi-annual periodicities,
their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical
clustering were used to identify predictors of influenza seasonal characteristics
and define epidemiologically-relevant regions. The annual periodicity of
influenza A epidemics increased with latitude (mean amplitude of annual cycle
standardized by mean incidence, 140% [95% CI 128%-151%] in the north versus 37%
[95% CI 27%-47%] in the south, p<0.0001). Epidemics peaked in January-February in
Northern China (latitude >=33 degrees N) and April-June in southernmost regions
(latitude <27 degrees N). Provinces at intermediate latitudes experienced
dominant semi-annual influenza A periodicity with peaks in January-February and
June-August (periodicity ratio >0.6 in provinces located within 27.4 degrees N
31.3 degrees N, slope of latitudinal gradient with latitude -0.016 [95% CI -0.025
to -0.008], p<0.001). In contrast, influenza B activity predominated in colder
months throughout most of China. Climate factors were the strongest predictors of
influenza seasonality, including minimum temperature, hours of sunshine, and
maximum rainfall. Our main study limitations include a short surveillance period
and sparse influenza sampling in some of the southern provinces. CONCLUSIONS:
Regional-specific influenza vaccination strategies would be optimal in China; in
particular, annual campaigns should be initiated 4-6 months apart in Northern and
Southern China. Influenza surveillance should be strengthened in mid-latitude
provinces, given the complexity of seasonal patterns in this region. More
broadly, our findings are consistent with the role of climatic factors on
influenza transmission dynamics. Please see later in the article for the Editors'
Summary.
PMID- 24348205
TI - HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the
Substrate Recognition Pattern.
AB - Drug resistance of HIV-1 protease alters the balance in the molecular recognition
events in favor of substrate processing versus inhibitor binding. To develop
robust inhibitors targeting ensembles of drug-resistant variants, the code of
this balance needs to be cracked. For this purpose, the principles governing the
substrate recognition are required to be revealed. Previous crystallographic
studies on the WT protease-substrate complexes showed that the substrates have a
conserved consensus volume in the protease active site despite their low sequence
homology. This consensus volume is termed as the substrate envelope. The
substrate envelope was recently reevaluated by taking the substrate dynamics into
account, and the dynamic substrate envelope was reported to better define the
substrate specificity for HIV-1 protease. Drug resistance occurs mostly through
mutations in the protease, occasionally accompanied by cleavage site mutations.
In this study, three coevolved protease-substrate complexes (AP2VNC-p1V82A,
LP1'Fp1-p6D30N/N88D, and SP3'Np1-p6D30N/N88D) were investigated for structural
and dynamic properties by molecular modeling and dynamics simulations. The
results show the substrate envelope is preserved by these cleavage site mutations
in the presence of drug-resistance mutations in the protease, if not enhanced.
This study on the conformational and mutational ensembles of protease-substrate
complexes validates the substrate envelope as the substrate recognition motif for
HIV-1 protease. The substrate envelope hypothesis allows for the elucidation of
possible drug resistance mutation patterns in the polyprotein cleavage sites.
PMID- 24348206
TI - High-Resolution Free-Energy Landscape Analysis of alpha-Helical Protein Folding:
HP35 and Its Double Mutant.
AB - The free-energy landscape can provide a quantitative description of folding
dynamics, if determined as a function of an optimally chosen reaction coordinate.
Here, we construct the optimal coordinate and the associated free-energy profile
for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based
on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci.
U.S.A.2012, 109, 17845]. From the obtained profiles, we directly determine such
basic properties of folding dynamics as the configurations of the minima and
transition states (TS), the formation of secondary structure and hydrophobic core
during the folding process, the value of the pre-exponential factor and its
relation to the transition path times, the relation between the autocorrelation
times in TS and minima. We also present an investigation of the accuracy of the
pre-exponential factor estimation based on the transition-path times. Four
different estimations of the pre-exponential factor for both proteins give k0-1
values of approximately a few tens of nanoseconds. Our analysis gives detailed
information about folding of the proteins and can serve as a rigorous common
language for extensive comparison between experiment and simulation.
PMID- 24348208
TI - Hypoxia and DNA repair.
AB - Hypoxia is a characteristic feature of solid tumors and occurs very early in
neoplastic development. Hypoxia transforms cell physiology in multiple ways, with
profound changes in cell metabolism, cell growth, susceptibility to apoptosis,
induction of angiogenesis, and increased motility. Over the past 20 years, our
lab has determined that hypoxia also induces genetic instability. We have
conducted a large series of experiments revealing that this instability occurs
through the alteration of DNA repair pathways, including nucleotide excision
repair, DNA mismatch repair, and homology dependent repair. Our work suggests
that hypoxia, as a key component of solid tumors, can drive cancer progression
through its impact on genomic integrity. However, the acquired changes in DNA
repair that are induced by hypoxia may also render hypoxic cancer cells
vulnerable to tailored strategies designed to exploit these changes.
PMID- 24348209
TI - Investigations of homologous recombination pathways and their regulation.
AB - The DNA double-strand break (DSB), arising from exposure to ionizing radiation or
various chemotherapeutic agents or from replication fork collapse, is among the
most dangerous of chromosomal lesions. DSBs are highly cytotoxic and can lead to
translocations, deletions, duplications, or mutations if mishandled. DSBs are
eliminated by either homologous recombination (HR), which uses a homologous
template to guide accurate repair, or by nonhomologous end joining (NHEJ), which
simply rejoins the two broken ends after damaged nucleotides have been removed.
HR generates error-free repair products and is also required for generating
chromosome arm crossovers between homologous chromosomes in meiotic cells. The HR
reaction includes several distinct steps: resection of DNA ends, homologous DNA
pairing, DNA synthesis, and processing of HR intermediates. Each occurs in a
highly regulated fashion utilizing multiple protein factors. These steps are
being elucidated using a combination of genetic tools, cell-based assays, and in
vitro reconstitution with highly purified HR proteins. In this review, we
summarize contributions from our laboratory at Yale University in understanding
HR mechanisms in eukaryotic cells.
PMID- 24348210
TI - Cellular roles of DNA polymerase beta.
AB - Since its discovery and purification in 1971, DNA polymerase beta (Pol beta) is
one of the most well-studied DNA polymerases. Pol beta is a key enzyme in the
base excision repair (BER) pathway that functions in gap filling DNA synthesis
subsequent to the excision of damaged DNA bases. A major focus of our studies is
on the cellular roles of Pol beta. We have shown that germline and tumor
associated variants of Pol beta catalyze aberrant BER that leads to genomic
instability and cellular transformation. Our studies suggest that Pol beta is
critical for the maintenance of genomic stability and that it is a tumor
suppressor. We have also shown that Pol beta functions during Prophase I of
meiosis. Pol beta localizes to the synaptonemal complex and is critical for
removal of the Spo11 complex from the 5' ends of double-strand breaks. Studies
with Pol beta mutant mice are currently being undertaken to more clearly
understand the function of Pol beta during meiosis. In this review, we will
highlight our contributions from our studies of Pol beta germline and cancer
associated variants.
PMID- 24348211
TI - Triplex-induced DNA damage response.
AB - Cellular DNA damage response is critical to preserving genomic integrity
following exposure to genotoxic stress. A complex series of networks and
signaling pathways become activated after DNA damage and trigger the appropriate
cellular response, including cell cycle arrest, DNA repair, and apoptosis. The
response elicited is dependent upon the type and extent of damage sustained, with
the ultimate goal of preventing propagation of the damaged DNA. A major focus of
our studies is to determine the cellular pathways involved in processing damage
induced by altered helical structures, specifically triplexes. Our lab has
demonstrated that the TFIIH factor XPD occupies a central role in triggering
apoptosis in response to triplex-induced DNA strand breaks. We have shown that
XPD co-localizes with gammaH2AX, and its presence is required for the
phosphorylation of H2AX tyrosine142, which stimulates the signaling pathway to
recruit pro-apoptotic factors to the damage site. Herein, we examine the cellular
pathways activated in response to triplex formation and discuss our finding that
suggests that XPD-dependent apoptosis plays a role in preserving genomic
integrity in the presence of excessive structurally induced DNA damage.
PMID- 24348212
TI - BRCA2: one small step for DNA repair, one giant protein purified.
AB - DNA damage, malfunctions in DNA repair, and genomic instability are processes
that intersect at the crossroads of carcinogenesis. Underscoring the importance
of DNA repair in breast and ovarian tumorigenesis is the familial inherited
cancer predisposition gene BRCA2. The role of BRCA2 in DNA double-strand break
repair was first revealed based on its interaction with RAD51, a central player
in homologous recombination. The RAD51 protein forms a nucleoprotein filament on
single-stranded DNA, invades a DNA duplex, and initiates a search for homology.
Once a homologous DNA sequence is found, the DNA is used as a template for the
high-fidelity repair of the DNA break. Many of the biochemical features that
allow BRCA2 to choreograph the activities of RAD51 have been elucidated and
include: targeting RAD51 to single-stranded DNA while inhibiting binding to
dsDNA, reducing the ATPase activity of RAD51, and facilitating the displacement
of the single-strand DNA binding protein, Replication Protein A. These
reinforcing activities of BRCA2 culminate in the correct positioning of RAD51
onto a processed DNA double-strand break and initiate its faithful repair by
homologous recombination. In this review, I will address current biochemical data
concerning the BRCA2 protein and highlight unanswered questions regarding BRCA2
function in homologous recombination and cancer.
PMID- 24348213
TI - Fanconi anemia: a signal transduction and DNA repair pathway.
AB - Fanconi anemia (FA) is a fascinating, rare genetic disorder marked by congenital
defects, bone marrow failure, and cancer susceptibility. Research in recent years
has led to the elucidation of FA as a DNA repair disorder and involved multiple
pathways as well as having wide applicability to common cancers, including
breast, ovarian, and head and neck. This review will describe the clinical
aspects of FA as well as the current state of its molecular pathophysiology. In
particular, work from the Kupfer laboratory will be described that demonstrates
how the FA pathway interacts with multiple DNA repair pathways, including the
mismatch repair system and signal transduction pathway of the DNA damage
response.
PMID- 24348214
TI - Early days of DNA repair: discovery of nucleotide excision repair and homology
dependent recombinational repair.
AB - The discovery of nucleotide excision repair in 1964 showed that DNA could be
repaired by a mechanism that removed the damaged section of a strand and replaced
it accurately by using the remaining intact strand as the template. This result
showed that DNA could be actively metabolized in a process that had no precedent.
In 1968, experiments describing postreplication repair, a process dependent on
homologous recombination, were reported. The authors of these papers were either
at Yale University or had prior Yale connections. Here we recount some of the
events leading to these discoveries and consider the impact on further research
at Yale and elsewhere.
PMID- 24348215
TI - DNA damage tolerance and a web of connections with DNA repair at Yale.
AB - This short article summarizes some of the research carried out recently by my
laboratory colleagues on the function of DNA polymerase zeta (polzeta) in
mammalian cells. Some personal background is also described, relevant to research
associations with Yale University and its continuing influence. Polzeta is
involved in the bypass of many DNA lesions by translesion DNA synthesis and is
responsible for the majority of DNA damage-induced point mutagenesis in mammalian
cells (including human cells), as well as in yeast. We also found that the
absence of this enzyme leads to gross chromosomal instability in mammalian cells
and increased spontaneous tumorigenesis in mice. Recently, we discovered a
further unexpectedly critical role for polzeta: it plays an essential role in
allowing continued rapid proliferation of cells and tissues. These observations
and others indicate that polzeta engages frequently during DNA replication to
bypass and tolerate DNA lesions or unusual DNA structures that are barriers for
the normal DNA replication machinery.
PMID- 24348216
TI - The awakening of DNA repair at Yale.
AB - As a graduate student with Professor Richard Setlow at Yale in the late 1950s, I
studied the effects of ultraviolet and visible light on the syntheses of DNA,
RNA, and protein in bacteria. I reflect upon my research in the Yale Biophysics
Department, my subsequent postdoctoral experiences, and the eventual analyses in
the laboratories of Setlow, Paul Howard-Flanders, and myself that constituted the
discovery of the ubiquitous pathway of DNA excision repair in the early 1960s. I
then offer a brief perspective on a few more recent developments in the
burgeoning DNA repair field and their relationships to human disease.
PMID- 24348217
TI - Nanotechnology in medicine: nanofilm biomaterials.
AB - By interrogating nature at the length scale of important biological molecules
(proteins, DNA), nanotechnology offers great promise to biomedicine. We review
here our recent work on nanofilm biomaterials: "nanoscopically" thin, functional,
polymer-based films serving as biocompatible interfaces. In one thrust, films
containing carbon nanotubes are shown to be highly antimicrobial and, thus, to be
promising as biomedical device materials inherently resistive to microbial
infection. In another thrust, strategies are developed toward films of
independently controllable bioactivity and mechanical rigidity - two key
variables governing typical biological responses.
PMID- 24348219
TI - How radiotherapy was historically used to treat pneumonia: could it be useful
today?
AB - X-ray therapy was used to treat pneumonia during the first half of the 20th
century. Fifteen studies report that approximately 700 cases of bacterial (lobar
and bronchopneumonia), sulfanilamide non-responsive, interstitial, and atypical
pneumonia were effectively treated by low doses of X-rays, leading to disease
resolution, based on clinical symptoms, objective disease biomarkers, and
mortality incidence. The capacity of the X-ray treatment to reduce mortality was
similar to serum therapy and sulfonamide treatment during the same time period.
Studies with four experimental animal models (i.e., mice, guinea pig, cat, and
dog) with bacterial and viral pneumonia supported the clinical findings. The
mechanism by which the X-ray treatment acts upon pneumonia involves the induction
of an anti-inflammatory phenotype that leads to a rapid reversal of clinical
symptoms, facilitating disease resolution. The capacity of low doses of X-rays to
suppress inflammatory responses is a significant new concept with widespread
biomedical and therapeutic applications.
PMID- 24348220
TI - Lost trust: a yellow fever patient response.
AB - In the 19th century, yellow fever thrived in the tropical, urban trade centers
along the American Gulf Coast. Industrializing and populated, New Orleans and
Memphis made excellent habitats for the yellow fever-carrying Aedes aegypti
mosquitoes and the virulence they imparted on their victims. Known for its
jaundice and black, blood-filled vomit, the malady terrorized the region for
decades, sometimes claiming tens of thousands of lives during the near annual
summertime outbreaks. In response to the failing medical community, a small,
pronounced population of sick and healthy laypeople openly criticized the efforts
to rid the Gulf region of yellow jack. Utilizing newspapers and cartoons to
vocalize their opinions, these critics doubted and mocked the medical community,
contributing to the regional and seasonal dilemma yellow fever posed for the
American South. These sentient expressions prove to be an early example of
patient distrust toward caregivers, a current problem in clinical heath care.
PMID- 24348218
TI - Microvascular targets for anti-fibrotic therapeutics.
AB - Fibrosis is characterized by excessive extracellular matrix deposition and is the
pathological outcome of repetitive tissue injury in many disorders. The
accumulation of matrix disrupts the structure and function of the native tissue
and can affect multiple organs including the lungs, heart, liver, and skin.
Unfortunately, current therapies against the deadliest and most common fibrosis
are ineffective. The pathogenesis of fibrosis is the result of aberrant wound
healing, therefore, the microvasculature plays an important role, contributing
through regulation of leukocyte recruitment, inflammation, and angiogenesis.
Further exacerbating the condition, microvascular endothelial cells and pericytes
can transdifferentiate into matrix depositing myofibroblasts. The contribution of
the microvasculature to fibrotic progression makes its cellular components and
acellular products attractive therapeutic targets. In this review, we examine
many of the cytokine, matrix, and cellular microvascular components involved in
fibrosis and discuss their potential as targets for fibrotic therapies with a
particular focus on developing nanotechnologies.
PMID- 24348221
TI - Near-peer teaching in a required third-year clerkship.
AB - Students who teach less experienced students within the same educational program
are known as near-peer teachers. A number of studies have shown that near-peers
are effective teachers in preclinical courses such as anatomy and physical
examination. We hypothesized that near-peers could also be effective teachers in
a clinical clerkship. We report on a pilot study in which near-peers participated
in a training session and then taught a brief problem-focused skills curriculum
to third-year students during a required ambulatory medicine rotation. The
clerkship students assigned high ratings to the near-peer teachers, both on an
absolute scale and relative to faculty. The results suggest that including near
peers as teachers in a clinical clerkship may be appropriate and that this
concept deserves further investigation.
PMID- 24348222
TI - Creating comprehensive, youth centered, culturally appropriate sex education:
What do young gay, bisexual and questioning men want?
AB - We examined young gay, bisexual and questioning men's (YGBQM) experiences with
school-based sex education as they sought to learn about sex and sexual health,
and their suggestions for improving same-sex education resources. Thematic
analysis of 30 in-depth interviews with YGBQM (ages 18-24) underscored the
discrepancies between the existing school-based sex education curricula and
YGBQM's perceived sex education needs. Our results show that many youths'
sexuality and same-sex sexual behaviors are excluded in sex education lessons;
however, YGBQM noted that they sought out other resources (e.g., websites) to
answer their questions. We discuss YGBQM's ideas for the creation of a sex and
sexual health website that would be tailored for youth like themselves, including
topics and features that an ideal website would contain. In addition, we present
recommended changes to existing school-based sexual education curricula.
PMID- 24348223
TI - Heterogeneity, mixing, and the spatial scales of mosquito-borne pathogen
transmission.
AB - The Ross-Macdonald model has dominated theory for mosquito-borne pathogen
transmission dynamics and control for over a century. The model, like many other
basic population models, makes the mathematically convenient assumption that
populations are well mixed; i.e., that each mosquito is equally likely to bite
any vertebrate host. This assumption raises questions about the validity and
utility of current theory because it is in conflict with preponderant empirical
evidence that transmission is heterogeneous. Here, we propose a new dynamic
framework that is realistic enough to describe biological causes of heterogeneous
transmission of mosquito-borne pathogens of humans, yet tractable enough to
provide a basis for developing and improving general theory. The framework is
based on the ecological context of mosquito blood meals and the fine-scale
movements of individual mosquitoes and human hosts that give rise to
heterogeneous transmission. Using this framework, we describe pathogen dispersion
in terms of individual-level analogues of two classical quantities: vectorial
capacity and the basic reproductive number, R0. Importantly, this framework
explicitly accounts for three key components of overall heterogeneity in
transmission: heterogeneous exposure, poor mixing, and finite host numbers. Using
these tools, we propose two ways of characterizing the spatial scales of
transmission--pathogen dispersion kernels and the evenness of mixing across
scales of aggregation--and demonstrate the consequences of a model's choice of
spatial scale for epidemic dynamics and for estimation of R0, both by a priori
model formulas and by inference of the force of infection from time-series data.
PMID- 24348224
TI - Next-generation sequence assembly: four stages of data processing and
computational challenges.
AB - Decoding DNA symbols using next-generation sequencers was a major breakthrough in
genomic research. Despite the many advantages of next-generation sequencers,
e.g., the high-throughput sequencing rate and relatively low cost of sequencing,
the assembly of the reads produced by these sequencers still remains a major
challenge. In this review, we address the basic framework of next-generation
genome sequence assemblers, which comprises four basic stages: preprocessing
filtering, a graph construction process, a graph simplification process, and
postprocessing filtering. Here we discuss them as a framework of four stages for
data analysis and processing and survey variety of techniques, algorithms, and
software tools used during each stage. We also discuss the challenges that face
current assemblers in the next-generation environment to determine the current
state-of-the-art. We recommend a layered architecture approach for constructing a
general assembler that can handle the sequences generated by different sequencing
platforms.
PMID- 24348225
TI - Epidemic spread on weighted networks.
AB - The contact structure between hosts shapes disease spread. Most network-based
models used in epidemiology tend to ignore heterogeneity in the weighting of
contacts between two individuals. However, this assumption is known to be at odds
with the data for many networks (e.g. sexual contact networks) and to have a
critical influence on epidemics' behavior. One of the reasons why models usually
ignore heterogeneity in transmission is that we currently lack tools to analyze
weighted networks, such that most studies rely on numerical simulations. Here, we
present a novel framework to estimate key epidemiological variables, such as the
rate of early epidemic expansion (r0) and the basic reproductive ratio (R0), from
joint probability distributions of number of partners (contacts) and number of
interaction events through which contacts are weighted. These distributions are
much easier to infer than the exact shape of the network, which makes the
approach widely applicable. The framework also allows for a derivation of the
full time course of epidemic prevalence and contact behaviour, which we validate
with numerical simulations on networks. Overall, incorporating more realistic
contact networks into epidemiological models can improve our understanding of the
emergence and spread of infectious diseases.
PMID- 24348226
TI - Metabolic constraint-based refinement of transcriptional regulatory networks.
AB - There is a strong need for computational frameworks that integrate different
biological processes and data-types to unravel cellular regulation. Current
efforts to reconstruct transcriptional regulatory networks (TRNs) focus primarily
on proximal data such as gene co-expression and transcription factor (TF)
binding. While such approaches enable rapid reconstruction of TRNs, the
overwhelming combinatorics of possible networks limits identification of
mechanistic regulatory interactions. Utilizing growth phenotypes and systems
level constraints to inform regulatory network reconstruction is an unmet
challenge. We present our approach Gene Expression and Metabolism Integrated for
Network Inference (GEMINI) that links a compendium of candidate regulatory
interactions with the metabolic network to predict their systems-level effect on
growth phenotypes. We then compare predictions with experimental phenotype data
to select phenotype-consistent regulatory interactions. GEMINI makes use of the
observation that only a small fraction of regulatory network states are
compatible with a viable metabolic network, and outputs a regulatory network that
is simultaneously consistent with the input genome-scale metabolic network model,
gene expression data, and TF knockout phenotypes. GEMINI preferentially recalls
gold-standard interactions (p-value = 10(-172)), significantly better than using
gene expression alone. We applied GEMINI to create an integrated metabolic
regulatory network model for Saccharomyces cerevisiae involving 25,000 regulatory
interactions controlling 1597 metabolic reactions. The model quantitatively
predicts TF knockout phenotypes in new conditions (p-value = 10(-14)) and
revealed potential condition-specific regulatory mechanisms. Our results suggest
that a metabolic constraint-based approach can be successfully used to help
reconstruct TRNs from high-throughput data, and highlights the potential of using
a biochemically-detailed mechanistic framework to integrate and reconcile
inconsistencies across different data-types. The algorithm and associated data
are available at https://sourceforge.net/projects/gemini-data/
PMID- 24348228
TI - Time scales in epigenetic dynamics and phenotypic heterogeneity of embryonic stem
cells.
AB - A remarkable feature of the self-renewing population of embryonic stem cells
(ESCs) is their phenotypic heterogeneity: Nanog and other marker proteins of ESCs
show large cell-to-cell variation in their expression level, which should
significantly influence the differentiation process of individual cells. The
molecular mechanism and biological implication of this heterogeneity, however,
still remain elusive. We address this problem by constructing a model of the core
gene-network of mouse ESCs. The model takes account of processes of
binding/unbinding of transcription factors, formation/dissolution of
transcription apparatus, and modification of histone code at each locus of genes
in the network. These processes are hierarchically interrelated to each other
forming the dynamical feedback loops. By simulating stochastic dynamics of this
model, we show that the phenotypic heterogeneity of ESCs can be explained when
the chromatin at the Nanog locus undergoes the large scale reorganization in
formation/dissolution of transcription apparatus, which should have the timescale
similar to the cell cycle period. With this slow transcriptional switching of
Nanog, the simulated ESCs fluctuate among multiple transient states, which can
trigger the differentiation into the lineage-specific cell states. From the
simulated transitions among cell states, the epigenetic landscape underlying
transitions is calculated. The slow Nanog switching gives rise to the wide basin
of ESC states in the landscape. The bimodal Nanog distribution arising from the
kinetic flow running through this ESC basin prevents transdifferentiation and
promotes the definite decision of the cell fate. These results show that the
distribution of timescales of the regulatory processes is decisively important to
characterize the fluctuation of cells and their differentiation process. The
analyses through the epigenetic landscape and the kinetic flow on the landscape
should provide a guideline to engineer cell differentiation.
PMID- 24348227
TI - Decipher the mechanisms of protein conformational changes induced by nucleotide
binding through free-energy landscape analysis: ATP binding to Hsp70.
AB - ATP regulates the function of many proteins in the cell by transducing its
binding and hydrolysis energies into protein conformational changes by mechanisms
which are challenging to identify at the atomic scale. Based on molecular
dynamics (MD) simulations, a method is proposed to analyze the structural changes
induced by ATP binding to a protein by computing the effective free-energy
landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The
method is applied to characterize the mechanism by which the binding of ATP to
the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate
binding domain (SBD). Unbiased MD simulations were performed for Hsp70-DnaK
chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations
revealed that the SBD does not interact with the NBD for DnaK in its nucleotide
free and ADP-bound states whereas the docking of the SBD was found in the ATP
bound state. The docked state induced by ATP binding found in MD is an
intermediate state between the initial nucleotide-free and final ATP-bound states
of Hsp70. The analysis of the FEL projected along the amino-acid sequence
permitted to identify a subset of 27 protein internal coordinates corresponding
to a network of 91 key residues involved in the conformational change induced by
ATP binding. Among the 91 residues, 26 are identified for the first time, whereas
the others were shown relevant for the allosteric communication of Hsp70 s in
several experiments and bioinformatics analysis. The FEL analysis revealed also
the origin of the ATP-induced structural modifications of the SBD recently
measured by Electron Paramagnetic Resonance. The pathway between the nucleotide
free and the intermediate state of DnaK was extracted by applying principal
component analysis to the subset of internal coordinates describing the
transition. The methodology proposed is general and could be applied to analyze
allosteric communication in other proteins.
PMID- 24348229
TI - Amino acid changes in disease-associated variants differ radically from variants
observed in the 1000 genomes project dataset.
AB - The 1000 Genomes Project data provides a natural background dataset for amino
acid germline mutations in humans. Since the direction of mutation is known, the
amino acid exchange matrix generated from the observed nucleotide variants is
asymmetric and the mutabilities of the different amino acids are very different.
These differences predominantly reflect preferences for nucleotide mutations in
the DNA (especially the high mutation rate of the CpG dinucleotide, which makes
arginine mutability very much higher than other amino acids) rather than
selection imposed by protein structure constraints, although there is evidence
for the latter as well. The variants occur predominantly on the surface of
proteins (82%), with a slight preference for sites which are more exposed and
less well conserved than random. Mutations to functional residues occur about
half as often as expected by chance. The disease-associated amino acid variant
distributions in OMIM are radically different from those expected on the basis of
the 1000 Genomes dataset. The disease-associated variants preferentially occur in
more conserved sites, compared to 1000 Genomes mutations. Many of the amino acid
exchange profiles appear to exhibit an anti-correlation, with common exchanges in
one dataset being rare in the other. Disease-associated variants exhibit more
extreme differences in amino acid size and hydrophobicity. More modelling of the
mutational processes at the nucleotide level is needed, but these observations
should contribute to an improved prediction of the effects of specific variants
in humans.
PMID- 24348230
TI - Forward and backward inference in spatial cognition.
AB - This paper shows that the various computations underlying spatial cognition can
be implemented using statistical inference in a single probabilistic model.
Inference is implemented using a common set of 'lower-level' computations
involving forward and backward inference over time. For example, to estimate
where you are in a known environment, forward inference is used to optimally
combine location estimates from path integration with those from sensory input.
To decide which way to turn to reach a goal, forward inference is used to compute
the likelihood of reaching that goal under each option. To work out which
environment you are in, forward inference is used to compute the likelihood of
sensory observations under the different hypotheses. For reaching sensory goals
that require a chaining together of decisions, forward inference can be used to
compute a state trajectory that will lead to that goal, and backward inference to
refine the route and estimate control signals that produce the required
trajectory. We propose that these computations are reflected in recent findings
of pattern replay in the mammalian brain. Specifically, that theta sequences
reflect decision making, theta flickering reflects model selection, and remote
replay reflects route and motor planning. We also propose a mapping of the above
computational processes onto lateral and medial entorhinal cortex and
hippocampus.
PMID- 24348231
TI - Modeling the afferent dynamics of the baroreflex control system.
AB - In this study we develop a modeling framework for predicting baroreceptor firing
rate as a function of blood pressure. We test models within this framework both
quantitatively and qualitatively using data from rats. The models describe three
components: arterial wall deformation, stimulation of mechanoreceptors located in
the BR nerve-endings, and modulation of the action potential frequency. The three
sub-systems are modeled individually following well-established biological
principles. The first submodel, predicting arterial wall deformation, uses blood
pressure as an input and outputs circumferential strain. The mechanoreceptor
stimulation model, uses circumferential strain as an input, predicting receptor
deformation as an output. Finally, the neural model takes receptor deformation as
an input predicting the BR firing rate as an output. Our results show that
nonlinear dependence of firing rate on pressure can be accounted for by taking
into account the nonlinear elastic properties of the artery wall. This was
observed when testing the models using multiple experiments with a single set of
parameters. We find that to model the response to a square pressure stimulus,
giving rise to post-excitatory depression, it is necessary to include an
integrate-and-fire model, which allows the firing rate to cease when the stimulus
falls below a given threshold. We show that our modeling framework in combination
with sensitivity analysis and parameter estimation can be used to test and
compare models. Finally, we demonstrate that our preferred model can exhibit all
known dynamics and that it is advantageous to combine qualitative and
quantitative analysis methods.
PMID- 24348233
TI - Moving education forward, again!
PMID- 24348232
TI - Ecological modeling from time-series inference: insight into dynamics and
stability of intestinal microbiota.
AB - The intestinal microbiota is a microbial ecosystem of crucial importance to human
health. Understanding how the microbiota confers resistance against enteric
pathogens and how antibiotics disrupt that resistance is key to the prevention
and cure of intestinal infections. We present a novel method to infer microbial
community ecology directly from time-resolved metagenomics. This method extends
generalized Lotka-Volterra dynamics to account for external perturbations. Data
from recent experiments on antibiotic-mediated Clostridium difficile infection is
analyzed to quantify microbial interactions, commensal-pathogen interactions, and
the effect of the antibiotic on the community. Stability analysis reveals that
the microbiota is intrinsically stable, explaining how antibiotic perturbations
and C. difficile inoculation can produce catastrophic shifts that persist even
after removal of the perturbations. Importantly, the analysis suggests a
subnetwork of bacterial groups implicated in protection against C. difficile. Due
to its generality, our method can be applied to any high-resolution ecological
time-series data to infer community structure and response to external stimuli.
PMID- 24348234
TI - Education in computational biology today and tomorrow.
PMID- 24348235
TI - Inferring developmental stage composition from gene expression in human malaria.
AB - In the current era of malaria eradication, reducing transmission is critical.
Assessment of transmissibility requires tools that can accurately identify the
various developmental stages of the malaria parasite, particularly those required
for transmission (sexual stages). Here, we present a method for estimating
relative amounts of Plasmodium falciparum asexual and sexual stages from gene
expression measurements. These are modeled using constrained linear regression to
characterize stage-specific expression profiles within mixed-stage populations.
The resulting profiles were analyzed functionally by gene set enrichment analysis
(GSEA), confirming differentially active pathways such as increased mitochondrial
activity and lipid metabolism during sexual development. We validated model
predictions both from microarrays and from quantitative RT-PCR (qRT-PCR)
measurements, based on the expression of a small set of key transcriptional
markers. This sufficient marker set was identified by backward selection from the
whole genome as available from expression arrays, targeting one sentinel marker
per stage. The model as learned can be applied to any new microarray or qRT-PCR
transcriptional measurement. We illustrate its use in vitro in inferring changes
in stage distribution following stress and drug treatment and in vivo in
identifying immature and mature sexual stage carriers within patient cohorts. We
believe this approach will be a valuable resource for staging lab and field
samples alike and will have wide applicability in epidemiological studies of
malaria transmission.
PMID- 24348236
TI - Exploring early stages of the chemical unfolding of proteins at the proteome
scale.
AB - After decades of using urea as denaturant, the kinetic role of this molecule in
the unfolding process is still undefined: does urea actively induce protein
unfolding or passively stabilize the unfolded state? By analyzing a set of 30
proteins (representative of all native folds) through extensive molecular
dynamics simulations in denaturant (using a range of force-fields), we derived
robust rules for urea unfolding that are valid at the proteome level.
Irrespective of the protein fold, presence or absence of disulphide bridges, and
secondary structure composition, urea concentrates in the first solvation shell
of quasi-native proteins, but with a density lower than that of the fully
unfolded state. The presence of urea does not alter the spontaneous vibration
pattern of proteins. In fact, it reduces the magnitude of such vibrations,
leading to a counterintuitive slow down of the atomic-motions that opposes
unfolding. Urea stickiness and slow diffusion is, however, crucial for unfolding.
Long residence urea molecules placed around the hydrophobic core are crucial to
stabilize partially open structures generated by thermal fluctuations. Our
simulations indicate that although urea does not favor the formation of partially
open microstates, it is not a mere spectator of unfolding that simply displaces
to the right of the folded <--> unfolded equilibrium. On the contrary, urea
actively favors unfolding: it selects and stabilizes partially unfolded
microstates, slowly driving the protein conformational ensemble far from the
native one and also from the conformations sampled during thermal unfolding.
PMID- 24348237
TI - GDI-mediated cell polarization in yeast provides precise spatial and temporal
control of Cdc42 signaling.
AB - Cell polarization is a prerequisite for essential processes such as cell
migration, proliferation or differentiation. The yeast Saccharomyces cerevisiae
under control of the GTPase Cdc42 is able to polarize without the help of
cytoskeletal structures and spatial cues through a pathway depending on its
guanine nucleotide dissociation inhibitor (GDI) Rdi1. To develop a fundamental
understanding of yeast polarization we establish a detailed mechanistic model of
GDI-mediated polarization. We show that GDI-mediated polarization provides
precise spatial and temporal control of Cdc42 signaling and give experimental
evidence for our findings. Cell cycle induced changes of Cdc42 regulation enhance
positive feedback loops of active Cdc42 production, and thereby allow
simultaneous switch-like regulation of focused polarity and Cdc42 activation.
This regulation drives the direct formation of a unique polarity cluster with
characteristic narrowing dynamics, as opposed to the previously proposed
competition between transient clusters. As the key components of the studied
system are conserved among eukaryotes, we expect our findings also to apply to
cell polarization in other organisms.
PMID- 24348239
TI - Aspergillus fumigatus--what makes the species a ubiquitous human fungal pathogen?
PMID- 24348240
TI - Dual expression profile of type VI secretion system immunity genes protects
pandemic Vibrio cholerae.
AB - The Vibrio cholerae type VI secretion system (T6SS) assembles as a molecular
syringe that injects toxic protein effectors into both eukaryotic and prokaryotic
cells. We previously reported that the V. cholerae O37 serogroup strain V52
maintains a constitutively active T6SS to kill other Gram-negative bacteria while
being immune to attack by kin bacteria. The pandemic O1 El Tor V. cholerae strain
C6706 is T6SS-silent under laboratory conditions as it does not produce T6SS
structural components and effectors, and fails to kill Escherichia coli prey.
Yet, C6706 exhibits full resistance when approached by T6SS-active V52. These
findings suggested that an active T6SS is not required for immunity against T6SS
mediated virulence. Here, we describe a dual expression profile of the T6SS
immunity protein-encoding genes tsiV1, tsiV2, and tsiV3 that provides pandemic V.
cholerae strains with T6SS immunity and allows T6SS-silent strains to maintain
immunity against attacks by T6SS-active bacterial neighbors. The dual expression
profile allows transcription of the three genes encoding immunity proteins
independently of other T6SS proteins encoded within the same operon. One of these
immunity proteins, TsiV2, protects against the T6SS effector VasX which is
encoded immediately upstream of tsiV2. VasX is a secreted, lipid-binding protein
that we previously characterized with respect to T6SS-mediated virulence towards
the social amoeba Dictyostelium discoideum. Our data suggest the presence of an
internal promoter in the open reading frame of vasX that drives expression of the
downstream gene tsiV2. Furthermore, VasX is shown to act in conjunction with
VasW, an accessory protein to VasX, to compromise the inner membrane of
prokaryotic target cells. The dual regulatory profile of the T6SS immunity
protein-encoding genes tsiV1, tsiV2, and tsiV3 permits V. cholerae to tightly
control T6SS gene expression while maintaining immunity to T6SS activity.
PMID- 24348241
TI - Coronaviruses as DNA wannabes: a new model for the regulation of RNA virus
replication fidelity.
PMID- 24348243
TI - Innate lymphoid cells: new players in IL-17-mediated antifungal immunity.
PMID- 24348242
TI - The type-specific neutralizing antibody response elicited by a dengue vaccine
candidate is focused on two amino acids of the envelope protein.
AB - Dengue viruses are mosquito-borne flaviviruses that circulate in nature as four
distinct serotypes (DENV1-4). These emerging pathogens are responsible for more
than 100 million human infections annually. Severe clinical manifestations of
disease are predominantly associated with a secondary infection by a heterotypic
DENV serotype. The increased risk of severe disease in DENV-sensitized
populations significantly complicates vaccine development, as a vaccine must
simultaneously confer protection against all four DENV serotypes. Eliciting a
protective tetravalent neutralizing antibody response is a major goal of ongoing
vaccine development efforts. However, a recent large clinical trial of a
candidate live-attenuated DENV vaccine revealed low protective efficacy despite
eliciting a neutralizing antibody response, highlighting the need for a better
understanding of the humoral immune response against dengue infection. In this
study, we sought to identify epitopes recognized by serotype-specific
neutralizing antibodies elicited by monovalent DENV1 vaccination. We constructed
a panel of over 50 DENV1 structural gene variants containing substitutions at
surface-accessible residues of the envelope (E) protein to match the
corresponding DENV2 sequence. Amino acids that contribute to recognition by
serotype-specific neutralizing antibodies were identified as DENV mutants with
reduced sensitivity to neutralization by DENV1 immune sera, but not cross
reactive neutralizing antibodies elicited by DENV2 vaccination. We identified two
mutations (E126K and E157K) that contribute significantly to type-specific
recognition by polyclonal DENV1 immune sera. Longitudinal and cross-sectional
analysis of sera from 24 participants of a phase I clinical study revealed a
markedly reduced capacity to neutralize a E126K/E157K DENV1 variant. Sera from
77% of subjects recognized the E126K/E157K DENV1 variant and DENV2 equivalently
(<3-fold difference). These data indicate the type-specific component of the
DENV1 neutralizing antibody response to vaccination is strikingly focused on just
two amino acids of the E protein. This study provides an important step towards
deconvoluting the functional complexity of DENV serology following vaccination.
PMID- 24348244
TI - Balancing stability and flexibility within the genome of the pathogen
Cryptococcus neoformans.
PMID- 24348245
TI - CRISPR-Cas immunity against phages: its effects on the evolution and survival of
bacterial pathogens.
PMID- 24348246
TI - Emerging functions for the Staphylococcus aureus RNome.
AB - Staphylococcus aureus is a leading pathogen for animals and humans, not only
being one of the most frequently isolated bacteria in hospital-associated
infections but also causing diseases in the community. To coordinate the
expression of its numerous virulence genes for growth and survival, S. aureus
uses various signalling pathways that include two-component regulatory systems,
transcription factors, and also around 250 regulatory RNAs. Biological roles have
only been determined for a handful of these sRNAs, including cis, trans, and cis
trans acting RNAs, some internally encoding small, functional peptides and others
possessing dual or multiple functions. Here we put forward an inventory of these
fascinating sRNAs; the proteins involved in their activities; and those involved
in stress response, metabolisms, and virulence.
PMID- 24348247
TI - LysM effectors: secreted proteins supporting fungal life.
PMID- 24348248
TI - Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
AB - Annual influenza epidemics and occasional pandemics pose a severe threat to human
health. Host cell factors required for viral spread but not for cellular survival
are attractive targets for novel approaches to antiviral intervention. The
cleavage activation of the influenza virus hemagglutinin (HA) by host cell
proteases is essential for viral infectivity. However, it is unknown which
proteases activate influenza viruses in mammals. Several candidates have been
identified in cell culture studies, leading to the concept that influenza viruses
can employ multiple enzymes to ensure their cleavage activation in the host.
Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in
mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic
2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice
were protected from weight loss, death and impairment of lung function. Also,
after infection with mono-basic H3N2 influenza A virus body weight loss and
survival was less severe in Tmprss2 mutant compared to wild type mice. As
expected, Tmprss2-deficient mice were not protected from viral spread and
pathology after infection with multi-basic H7N7 influenza A virus. In conclusion,
these results identify TMPRSS2 as a host cell factor essential for viral spread
and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.
PMID- 24348249
TI - Real-time imaging of the intracellular glutathione redox potential in the malaria
parasite Plasmodium falciparum.
AB - In the malaria parasite Plasmodium falciparum, the cellular redox potential
influences signaling events, antioxidant defense, and mechanisms of drug action
and resistance. Until now, the real-time determination of the redox potential in
malaria parasites has been limited because conventional approaches disrupt sub
cellular integrity. Using a glutathione biosensor comprising human glutaredoxin-1
linked to a redox-sensitive green fluorescent protein (hGrx1-roGFP2), we
systematically characterized basal values and drug-induced changes in the
cytosolic glutathione-dependent redox potential (EGSH) of drug-sensitive (3D7)
and resistant (Dd2) P. falciparum parasites. Via confocal microscopy, we
demonstrated that hGrx1-roGFP2 rapidly detects EGSH changes induced by oxidative
and nitrosative stress. The cytosolic basal EGSH of 3D7 and Dd2 were estimated to
be -314.2+/-3.1 mV and -313.9+/-3.4 mV, respectively, which is indicative of a
highly reducing compartment. We furthermore monitored short-, medium-, and long
term changes in EGSH after incubation with various redox-active compounds and
antimalarial drugs. Interestingly, the redox cyclers methylene blue and pyocyanin
rapidly changed the fluorescence ratio of hGrx1-roGFP2 in the cytosol of P.
falciparum, which can, however, partially be explained by a direct interaction
with the probe. In contrast, quinoline and artemisinin-based antimalarial drugs
showed strong effects on the parasites' EGSH after longer incubation times (24
h). As tested for various conditions, these effects were accompanied by a drop in
total glutathione concentrations determined in parallel with alternative methods.
Notably, the effects were generally more pronounced in the chloroquine-sensitive
3D7 strain than in the resistant Dd2 strain. Based on these results hGrx1-roGFP2
can be recommended as a reliable and specific biosensor for real-time
spatiotemporal monitoring of the intracellular EGSH in P. falciparum. Applying
this technique in further studies will enhance our understanding of redox
regulation and mechanisms of drug action and resistance in Plasmodium and might
also stimulate redox research in other pathogens.
PMID- 24348250
TI - Serotonergic chemosensory neurons modify the C. elegans immune response by
regulating G-protein signaling in epithelial cells.
AB - The nervous and immune systems influence each other, allowing animals to rapidly
protect themselves from changes in their internal and external environment.
However, the complex nature of these systems in mammals makes it difficult to
determine how neuronal signaling influences the immune response. Here we show
that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons,
modulates the immune response. Serotonin released from these cells acts, directly
or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in
these cells is required for the immune response to infection by the natural
pathogen Microbacterium nematophilum. Here we show that serotonin signaling
suppresses the innate immune response and limits the rate of pathogen clearance.
We show that C. elegans uses classical neurotransmitters to alter the immune
response. Serotonin released from sensory neurons may function to modify the
immune system in response to changes in the animal's external environment such as
the availability, or quality, of food.
PMID- 24348251
TI - Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to
target mitochondria and cause endothelial and epithelial apoptosis.
AB - Enterohemorrhagic Escherichia coli (EHEC) strains cause diarrhea and hemolytic
uremic syndrome resulting from toxin-mediated microvascular endothelial injury.
EHEC hemolysin (EHEC-Hly), a member of the RTX (repeats-in-toxin) family, is an
EHEC virulence factor of increasingly recognized importance. The toxin exists as
free EHEC-Hly and as EHEC-Hly associated with outer membrane vesicles (OMVs)
released by EHEC during growth. Whereas the free toxin is lytic towards human
endothelium, the biological effects of the OMV-associated EHEC-Hly on
microvascular endothelial and intestinal epithelial cells, which are the major
targets during EHEC infection, are unknown. Using microscopic, biochemical, flow
cytometry and functional analyses of human brain microvascular endothelial cells
(HBMEC) and Caco-2 cells we demonstrate that OMV-associated EHEC-Hly does not
lyse the target cells but triggers their apoptosis. The OMV-associated toxin is
internalized by HBMEC and Caco-2 cells via dynamin-dependent endocytosis of OMVs
and trafficked with OMVs into endo-lysosomal compartments. Upon endosome
acidification and subsequent pH drop, EHEC-Hly is separated from OMVs, escapes
from the lysosomes, most probably via its pore-forming activity, and targets
mitochondria. This results in decrease of the mitochondrial transmembrane
potential and translocation of cytochrome c to the cytosol, indicating EHEC-Hly
mediated permeabilization of the mitochondrial membranes. Subsequent activation
of caspase-9 and caspase-3 leads to apoptotic cell death as evidenced by DNA
fragmentation and chromatin condensation in the intoxicated cells. The ability of
OMV-associated EHEC-Hly to trigger the mitochondrial apoptotic pathway in human
microvascular endothelial and intestinal epithelial cells indicates a novel
mechanism of EHEC-Hly involvement in the pathogenesis of EHEC diseases. The OMV
mediated intracellular delivery represents a newly recognized mechanism for a
bacterial toxin to enter host cells in order to target mitochondria.
PMID- 24348252
TI - The genetic basis of Escherichia coli pathoadaptation to macrophages.
AB - Antagonistic interactions are likely important driving forces of the evolutionary
process underlying bacterial genome complexity and diversity. We hypothesized
that the ability of evolved bacteria to escape specific components of host innate
immunity, such as phagocytosis and killing by macrophages (MPhi), is a critical
trait relevant in the acquisition of bacterial virulence. Here, we used a
combination of experimental evolution, phenotypic characterization, genome
sequencing and mathematical modeling to address how fast, and through how many
adaptive steps, a commensal Escherichia coli (E. coli) acquire this virulence
trait. We show that when maintained in vitro under the selective pressure of host
MPhi commensal E. coli can evolve, in less than 500 generations, virulent clones
that escape phagocytosis and MPhi killing in vitro, while increasing their
pathogenicity in vivo, as assessed in mice. This pathoadaptive process is driven
by a mechanism involving the insertion of a single transposable element into the
promoter region of the E. coli yrfF gene. Moreover, transposition of the IS186
element into the promoter of Lon gene, encoding an ATP-dependent serine protease,
is likely to accelerate this pathoadaptive process. Competition between clones
carrying distinct beneficial mutations dominates the dynamics of the
pathoadaptive process, as suggested from a mathematical model, which reproduces
the observed experimental dynamics of E. coli evolution towards virulence. In
conclusion, we reveal a molecular mechanism explaining how a specific component
of host innate immunity can modulate microbial evolution towards pathogenicity.
PMID- 24348253
TI - Semen CD4+ T cells and macrophages are productively infected at all stages of SIV
infection in macaques.
AB - The mucosal events of HIV transmission have been extensively studied, but the
role of infected cells present in the genital and rectal secretions, and in the
semen, in particular, remains a matter of debate. As a prerequisite to a thorough
in vivo investigation of the early transmission events through infected cells, we
characterized in detail by multi-parameter flow cytometry the changes in macaque
seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages
and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real
time quantitative PCR targeting SIV DNA, we investigated the nature of the
infected cells on sorted semen leukocytes from macaques at different stages of
infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a
cell line permissive to SIV infection to assess their infectivity in vitro. We
found that primary infection induced strong local inflammation, which was
associated with an increase in the number of leukocytes in semen, both factors
having the potential to favor cell-associated virus transmission. Semen CD4(+) T
cells and macrophages were productively infected at all stages of infection and
were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed
activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69
expression was increased in semen T cells by SIV infection, at all stages of
infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1
and LFA-1. Altogether, we demonstrated that semen contains the two major SIV
target cells (CD4+ T cells and macrophages). Both cell types can be productively
infected at all stages of SIV infection and are endowed with markers that may
facilitate transmission of infection during sexual exposure.
PMID- 24348254
TI - The malarial serine protease SUB1 plays an essential role in parasite liver stage
development.
AB - Transmission of the malaria parasite to its vertebrate host involves an
obligatory exoerythrocytic stage in which extensive asexual replication of the
parasite takes place in infected hepatocytes. The resulting liver schizont
undergoes segmentation to produce thousands of daughter merozoites. These are
released to initiate the blood stage life cycle, which causes all the pathology
associated with the disease. Whilst elements of liver stage merozoite biology are
similar to those in the much better-studied blood stage merozoites, little is
known of the molecular players involved in liver stage merozoite production. To
facilitate the study of liver stage biology we developed a strategy for the rapid
production of complex conditional alleles by recombinase mediated engineering in
Escherichia coli, which we used in combination with existing Plasmodium berghei
deleter lines expressing Flp recombinase to study subtilisin-like protease 1
(SUB1), a conserved Plasmodium serine protease previously implicated in blood
stage merozoite maturation and egress. We demonstrate that SUB1 is not required
for the early stages of intrahepatic growth, but is essential for complete
development of the liver stage schizont and for production of hepatic merozoites.
Our results indicate that inhibitors of SUB1 could be used in prophylactic
approaches to control or block the clinically silent pre-erythrocytic stage of
the malaria parasite life cycle.
PMID- 24348255
TI - Phagocytosis escape by a Staphylococcus aureus protein that connects complement
and coagulation proteins at the bacterial surface.
AB - Upon contact with human plasma, bacteria are rapidly recognized by the complement
system that labels their surface for uptake and clearance by phagocytic cells.
Staphylococcus aureus secretes the 16 kD Extracellular fibrinogen binding protein
(Efb) that binds two different plasma proteins using separate domains: the Efb N
terminus binds to fibrinogen, while the C-terminus binds complement C3. In this
study, we show that Efb blocks phagocytosis of S. aureus by human neutrophils. In
vitro, we demonstrate that Efb blocks phagocytosis in plasma and in human whole
blood. Using a mouse peritonitis model we show that Efb effectively blocks
phagocytosis in vivo, either as a purified protein or when produced endogenously
by S. aureus. Mutational analysis revealed that Efb requires both its fibrinogen
and complement binding residues for phagocytic escape. Using confocal and
transmission electron microscopy we show that Efb attracts fibrinogen to the
surface of complement-labeled S. aureus generating a 'capsule'-like shield. This
thick layer of fibrinogen shields both surface-bound C3b and antibodies from
recognition by phagocytic receptors. This information is critical for future
vaccination attempts, since opsonizing antibodies may not function in the
presence of Efb. Altogether we discover that Efb from S. aureus uniquely escapes
phagocytosis by forming a bridge between a complement and coagulation protein.
PMID- 24348256
TI - Placental syncytium forms a biophysical barrier against pathogen invasion.
AB - Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is
bathed in maternal blood, and constitutes the main interface between fetus and
mother. Syncytiotrophoblasts are exposed to pathogens circulating in maternal
blood, and appear to have unique resistance mechanisms against microbial
invasion. These are due in part to the lack of intercellular junctions and their
receptors, the Achilles heel of polarized mononuclear epithelia. However, the
syncytium is immune to receptor-independent invasion as well, suggesting
additional general defense mechanisms against infection. The difficulty of
maintaining and manipulating primary human syncytiotrophoblasts in culture makes
it challenging to investigate the cellular and molecular basis of host defenses
in this unique tissue. Here we present a novel system to study placental
pathogenesis using murine trophoblast stem cells (mTSC) that can be
differentiated into syncytiotrophoblasts and recapitulate human placental
syncytium. Consistent with previous results in primary human organ cultures,
murine syncytiotrophoblasts were found to be resistant to infection with Listeria
monocytogenes via direct invasion and cell-to-cell spread. Atomic force
microscopy of murine syncytiotrophoblasts demonstrated that these cells have a
greater elastic modulus than mononuclear trophoblasts. Disruption of the
unusually dense actin structure--a diffuse meshwork of microfilaments--with
Cytochalasin D led to a decrease in its elastic modulus by 25%. This correlated
with a small but significant increase in invasion of L. monocytogenes into murine
and human syncytium. These results suggest that the syncytial actin cytoskeleton
may form a general barrier against pathogen entry in humans and mice. Moreover,
murine TSCs are a genetically tractable model system for the investigation of
specific pathways in syncytial host defenses.
PMID- 24348257
TI - Nodular inflammatory foci are sites of T cell priming and control of murine
cytomegalovirus infection in the neonatal lung.
AB - Neonates, including mice and humans, are highly susceptible to cytomegalovirus
(CMV) infection. However, many aspects of neonatal CMV infections such as viral
cell tropism, spatio-temporal distribution of the pathogen as well as genesis of
antiviral immunity are unknown. With the use of reporter mutants of the murine
cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal
infection in neonatal mice. Comparative analysis of neonatal and adult mice
revealed a delayed control of virus replication in the neonatal lung mucosa
explaining the pronounced systemic infection and disease in neonates. This
phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones
recognizing the viral protein M45 in neonates. We detected viral infection at the
single-cell level and observed myeloid cells forming "nodular inflammatory foci"
(NIF) in the neonatal lung. Co-localization of infected cells within NIFs was
associated with their disruption and clearance of the infection. By 2-photon
microscopy, we characterized how neonatal antigen-presenting cells (APC)
interacted with T cells and induced mature adaptive immune responses within such
NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV
replication and T cell priming but also as sites of infection control.
PMID- 24348259
TI - Wolbachia variants induce differential protection to viruses in Drosophila
melanogaster: a phenotypic and phylogenomic analysis.
AB - Wolbachia are intracellular bacterial symbionts that are able to protect various
insect hosts from viral infections. This tripartite interaction was initially
described in Drosophila melanogaster carrying wMel, its natural Wolbachia strain.
wMel has been shown to be genetically polymorphic and there has been a recent
change in variant frequencies in natural populations. We have compared the
antiviral protection conferred by different wMel variants, their titres and
influence on host longevity, in a genetically identical D. melanogaster host. The
phenotypes cluster the variants into two groups--wMelCS-like and wMel-like.
wMelCS-like variants give stronger protection against Drosophila C virus and
Flock House virus, reach higher titres and often shorten the host lifespan. We
have sequenced and assembled the genomes of these Wolbachia, and shown that the
two phenotypic groups are two monophyletic groups. We have also analysed a
virulent and over-replicating variant, wMelPop, which protects D. melanogaster
even better than the closely related wMelCS. We have found that a ~21 kb region
of the genome, encoding eight genes, is amplified seven times in wMelPop and may
be the cause of its phenotypes. Our results indicate that the more protective
wMelCS-like variants, which sometimes have a cost, were replaced by the less
protective but more benign wMel-like variants. This has resulted in a recent
reduction in virus resistance in D. melanogaster in natural populations
worldwide. Our work helps to understand the natural variation in wMel and its
evolutionary dynamics, and inform the use of Wolbachia in arthropod-borne disease
control.
PMID- 24348260
TI - Role of tomato lipoxygenase D in wound-induced jasmonate biosynthesis and plant
immunity to insect herbivores.
AB - In response to insect attack and mechanical wounding, plants activate the
expression of genes involved in various defense-related processes. A fascinating
feature of these inducible defenses is their occurrence both locally at the
wounding site and systemically in undamaged leaves throughout the plant. Wound
inducible proteinase inhibitors (PIs) in tomato (Solanum lycopersicum) provide an
attractive model to understand the signal transduction events leading from
localized injury to the systemic expression of defense-related genes. Among the
identified intercellular molecules in regulating systemic wound response of
tomato are the peptide signal systemin and the oxylipin signal jasmonic acid
(JA). The systemin/JA signaling pathway provides a unique opportunity to
investigate, in a single experimental system, the mechanism by which peptide and
oxylipin signals interact to coordinate plant systemic immunity. Here we describe
the characterization of the tomato suppressor of prosystemin-mediated responses8
(spr8) mutant, which was isolated as a suppressor of (pro)systemin-mediated
signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies,
including the inability to express wound-responsive genes, abnormal development
of glandular trichomes, and severely compromised resistance to cotton bollworm
(Helicoverpa armigera) and Botrytis cinerea. Map-based cloning studies
demonstrate that the spr8 mutant phenotype results from a point mutation in the
catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA
biosynthesis. We present evidence that overexpression of TomLoxD leads to
elevated wound-induced JA biosynthesis, increased expression of wound-responsive
genes and, therefore, enhanced resistance to insect herbivory attack and
necrotrophic pathogen infection. These results indicate that TomLoxD is involved
in wound-induced JA biosynthesis and highlight the application potential of this
gene for crop protection against insects and pathogens.
PMID- 24348261
TI - An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines
the size of the midbrain dopaminergic progenitor pool.
AB - MicroRNAs regulate gene expression in diverse physiological scenarios. Their role
in the control of morphogen related signaling pathways has been less studied,
particularly in the context of embryonic Central Nervous System (CNS)
development. Here, we uncover a role for microRNAs in limiting the spatiotemporal
range of morphogen expression and function. Wnt1 is a key morphogen in the
embryonic midbrain, and directs proliferation, survival, patterning and
neurogenesis. We reveal an autoregulatory negative feedback loop between the
transcription factor Lmx1b and a newly characterized microRNA, miR135a2, which
modulates the extent of Wnt1/Wnt signaling and the size of the dopamine
progenitor domain. Conditional gain of function studies reveal that Lmx1b
promotes Wnt1/Wnt signaling, and thereby increases midbrain size and dopamine
progenitor allocation. Conditional removal of Lmx1b has the opposite effect, in
that expansion of the dopamine progenitor domain is severely compromised. Next,
we provide evidence that microRNAs are involved in restricting dopamine
progenitor allocation. Conditional loss of Dicer1 in embryonic stem cells (ESCs)
results in expanded Lmx1a/b+ progenitors. In contrast, forced elevation of
miR135a2 during an early window in vivo phenocopies the Lmx1b conditional
knockout. When En1::Cre, but not Shh::Cre or Nes::Cre, is used for recombination,
the expansion of Lmx1a/b+ progenitors is selectively reduced. Bioinformatics and
luciferase assay data suggests that miR135a2 targets Lmx1b and many genes in the
Wnt signaling pathway, including Ccnd1, Gsk3b, and Tcf7l2. Consistent with this,
we demonstrate that this mutant displays reductions in the size of the Lmx1b/Wnt1
domain and range of canonical Wnt signaling. We posit that microRNA modulation of
the Lmx1b/Wnt axis in the early midbrain/isthmus could determine midbrain size
and allocation of dopamine progenitors. Since canonical Wnt activity has recently
been recognized as a key ingredient for programming ESCs towards a dopaminergic
fate in vitro, these studies could impact the rational design of such protocols.
PMID- 24348262
TI - Parathyroid-specific deletion of Klotho unravels a novel calcineurin-dependent
FGF23 signaling pathway that regulates PTH secretion.
AB - Klotho acts as a co-receptor for and dictates tissue specificity of circulating
FGF23. FGF23 inhibits PTH secretion, and reduced Klotho abundance is considered a
pathogenic factor in renal secondary hyperparathyroidism. To dissect the role of
parathyroid gland resident Klotho in health and disease, we generated mice with a
parathyroid-specific Klotho deletion (PTH-KL(-/-)). PTH-KL(-/-) mice had a normal
gross phenotype and survival; normal serum PTH and calcium; unaltered expression
of the PTH gene in parathyroid tissue; and preserved PTH response and sensitivity
to acute changes in serum calcium. Their PTH response to intravenous FGF23
delivery or renal failure did not differ compared to their wild-type littermates
despite disrupted FGF23-induced activation of the MAPK/ERK pathway. Importantly,
calcineurin-NFAT signaling, defined by increased MCIP1 level and nuclear
localization of NFATC2, was constitutively activated in PTH-KL(-/-) mice.
Treatment with the calcineurin-inhibitor cyclosporine A abolished FGF23-mediated
PTH suppression in PTH-KL(-/-) mice whereas wild-type mice remained responsive.
Similar results were observed in thyro-parathyroid explants ex vivo.
Collectively, we present genetic and functional evidence for a novel, Klotho
independent, calcineurin-mediated FGF23 signaling pathway in parathyroid glands
that mediates suppression of PTH. The presence of Klotho-independent FGF23
effects in a Klotho-expressing target organ represents a paradigm shift in the
conceptualization of FGF23 endocrine action.
PMID- 24348263
TI - A global in vivo Drosophila RNAi screen identifies a key role of ceramide
phosphoethanolamine for glial ensheathment of axons.
AB - Glia are of vital importance for all complex nervous system. One of the many
functions of glia is to insulate and provide trophic and metabolic support to
axons. Here, using glial-specific RNAi knockdown in Drosophila, we silenced 6930
conserved genes in adult flies to identify essential genes and pathways. Among
our screening hits, metabolic processes were highly represented, and genes
involved in carbohydrate and lipid metabolic pathways appeared to be essential in
glia. One critical pathway identified was de novo ceramide synthesis. Glial
knockdown of lace, a subunit of the serine palmitoyltransferase associated with
hereditary sensory and autonomic neuropathies in humans, resulted in ensheathment
defects of peripheral nerves in Drosophila. A genetic dissection study combined
with shotgun high-resolution mass spectrometry of lipids showed that levels of
ceramide phosphoethanolamine are crucial for axonal ensheathment by glia. A
detailed morphological and functional analysis demonstrated that the depletion of
ceramide phosphoethanolamine resulted in axonal defasciculation, slowed spike
propagation, and failure of wrapping glia to enwrap peripheral axons.
Supplementing sphingosine into the diet rescued the neuropathy in flies. Thus,
our RNAi study in Drosophila identifies a key role of ceramide
phosphoethanolamine in wrapping of axons by glia.
PMID- 24348264
TI - Tay bridge is a negative regulator of EGFR signalling and interacts with Erk and
Mkp3 in the Drosophila melanogaster wing.
AB - The regulation of Extracellular regulated kinase (Erk) activity is a key aspect
of signalling by pathways activated by extracellular ligands acting through
tyrosine kinase transmembrane receptors. In this process, participate proteins
with kinase activity that phosphorylate and activate Erk, as well as different
phosphatases that inactivate Erk by de-phosphorylation. The state of Erk
phosphorylation affects not only its activity, but also its subcellular
localization, defining the repertoire of Erk target proteins, and consequently,
the cellular response to Erk. In this work, we characterise Tay bridge as a novel
component of the EGFR/Erk signalling pathway. Tay bridge is a large nuclear
protein with a domain of homology with human AUTS2, and was previously identified
due to the neuronal phenotypes displayed by loss-of-function mutations. We show
that Tay bridge antagonizes EGFR signalling in the Drosophila melanogaster wing
disc and other tissues, and that the protein interacts with both Erk and Mkp3. We
suggest that Tay bridge constitutes a novel element involved in the regulation of
Erk activity, acting as a nuclear docking for Erk that retains this protein in an
inactive form in the nucleus.
PMID- 24348265
TI - Genetic recombination is targeted towards gene promoter regions in dogs.
AB - The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for
recombination hotspot localization has provided considerable insight into the
mechanisms by which recombination is initiated in mammals. However, uniquely
amongst mammals, canids appear to lack a functional version of PRDM9 and may
therefore provide a model for understanding recombination that occurs in the
absence of PRDM9, and thus how PRDM9 functions to shape the recombination
landscape. We have constructed a fine-scale genetic map from patterns of linkage
disequilibrium assessed using high-throughput sequence data from 51 free-ranging
dogs, Canis lupus familiaris. While broad-scale properties of recombination
appear similar to other mammalian species, our fine-scale estimates indicate that
canine highly elevated recombination rates are observed in the vicinity of CpG
rich regions including gene promoter regions, but show little association with
H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic
data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion
is a plausible mechanism by which the high CpG content of the dog genome could
have occurred.
PMID- 24348266
TI - Alcohol-induced histone acetylation reveals a gene network involved in alcohol
tolerance.
AB - Sustained or repeated exposure to sedating drugs, such as alcohol, triggers
homeostatic adaptations in the brain that lead to the development of drug
tolerance and dependence. These adaptations involve long-term changes in the
transcription of drug-responsive genes as well as an epigenetic restructuring of
chromosomal regions that is thought to signal and maintain the altered
transcriptional state. Alcohol-induced epigenetic changes have been shown to be
important in the long-term adaptation that leads to alcohol tolerance and
dependence endophenotypes. A major constraint impeding progress is that alcohol
produces a surfeit of changes in gene expression, most of which may not make any
meaningful contribution to the ethanol response under study. Here we used a novel
genomic epigenetic approach to find genes relevant for functional alcohol
tolerance by exploiting the commonalities of two chemically distinct alcohols. In
Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross
tolerance, indicating that they share a common mechanism for producing tolerance.
We surveyed the genome-wide changes in histone acetylation that occur in response
to these drugs. Each drug induces modifications in a large number of genes. The
genes that respond similarly to either treatment, however, represent a subgroup
enriched for genes important for the common tolerance response. Genes were
functionally tested for behavioral tolerance to the sedative effects of ethanol
and benzyl alcohol using mutant and inducible RNAi stocks. We identified a
network of genes that are essential for the development of tolerance to sedation
by alcohol.
PMID- 24348267
TI - Expanding the marine virosphere using metagenomics.
AB - Viruses infecting prokaryotic cells (phages) are the most abundant entities of
the biosphere and contain a largely uncharted wealth of genomic diversity. They
play a critical role in the biology of their hosts and in ecosystem functioning
at large. The classical approaches studying phages require isolation from a pure
culture of the host. Direct sequencing approaches have been hampered by the small
amounts of phage DNA present in most natural habitats and the difficulty in
applying meta-omic approaches, such as annotation of small reads and assembly.
Serendipitously, it has been discovered that cellular metagenomes of highly
productive ocean waters (the deep chlorophyll maximum) contain significant
amounts of viral DNA derived from cells undergoing the lytic cycle. We have taken
advantage of this phenomenon to retrieve metagenomic fosmids containing viral DNA
from a Mediterranean deep chlorophyll maximum sample. This method allowed
description of complete genomes of 208 new marine phages. The diversity of these
genomes was remarkable, contributing 21 genomic groups of tailed bacteriophages
of which 10 are completely new. Sequence based methods have allowed host
assignment to many of them. These predicted hosts represent a wide variety of
important marine prokaryotic microbes like members of SAR11 and SAR116 clades,
Cyanobacteria and also the newly described low GC Actinobacteria. A metavirome
constructed from the same habitat showed that many of the new phage genomes were
abundantly represented. Furthermore, other available metaviromes also indicated
that some of the new phages are globally distributed in low to medium latitude
ocean waters. The availability of many genomes from the same sample allows a
direct approach to viral population genomics confirming the remarkable mosaicism
of phage genomes.
PMID- 24348268
TI - MAN1B1 deficiency: an unexpected CDG-II.
AB - Congenital disorders of glycosylation (CDG) are a group of rare metabolic
diseases, due to impaired protein and lipid glycosylation. In the present study,
exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved
CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All
individuals presented slight facial dysmorphism, psychomotor retardation and
truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2
mannosidase acting as a key factor in glycoprotein quality control by targeting
misfolded proteins for ER-associated degradation (ERAD). However, recent studies
indicated a Golgi localization of the endogenous MAN1B1, suggesting a more
complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1
is indeed localized to the Golgi complex instead of the ER. Furthermore, we
observed an altered Golgi morphology in all patients' cells, with marked
dilatation and fragmentation. We hypothesize that part of the phenotype is
associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1
to a Golgi glycosylation disorder. Additionally, our results support the recent
findings on MAN1B1 localization. However, more work is needed to pinpoint the
exact function of MAN1B1 in glycoprotein quality control, and to understand the
pathophysiology of its deficiency.
PMID- 24348269
TI - Sumoylated NHR-25/NR5A regulates cell fate during C. elegans vulval development.
AB - Individual metazoan transcription factors (TFs) regulate distinct sets of genes
depending on cell type and developmental or physiological context. The precise
mechanisms by which regulatory information from ligands, genomic sequence
elements, co-factors, and post-translational modifications are integrated by TFs
remain challenging questions. Here, we examine how a single regulatory input,
sumoylation, differentially modulates the activity of a conserved C. elegans
nuclear hormone receptor, NHR-25, in different cell types. Through a combination
of yeast two-hybrid analysis and in vitro biochemistry we identified the single
C. elegans SUMO (SMO-1) as an NHR-25 interacting protein, and showed that NHR-25
is sumoylated on at least four lysines. Some of the sumoylation acceptor sites
are in common with those of the NHR-25 mammalian orthologs SF-1 and LRH-1,
demonstrating that sumoylation has been strongly conserved within the NR5A
family. We showed that NHR-25 bound canonical SF-1 binding sequences to regulate
transcription, and that NHR-25 activity was enhanced in vivo upon loss of
sumoylation. Knockdown of smo-1 mimicked NHR-25 overexpression with respect to
maintenance of the 3 degrees cell fate in vulval precursor cells (VPCs) during
development. Importantly, however, overexpression of unsumoylatable alleles of
NHR-25 revealed that NHR-25 sumoylation is critical for maintaining 3 degrees
cell fate. Moreover, SUMO also conferred formation of a developmental time
dependent NHR-25 concentration gradient across the VPCs. That is, accumulation of
GFP-tagged NHR-25 was uniform across VPCs at the beginning of development, but as
cells began dividing, a smo-1-dependent NHR-25 gradient formed with highest
levels in 1 degrees fated VPCs, intermediate levels in 2 degrees fated VPCs,
and low levels in 3 degrees fated VPCs. We conclude that sumoylation operates at
multiple levels to affect NHR-25 activity in a highly coordinated spatial and
temporal manner.
PMID- 24348270
TI - A trans-acting protein effect causes severe eye malformation in the Mp mouse.
AB - Mp is an irradiation-induced mouse mutation associated with microphthalmia,
micropinna and hind limb syndactyly. We show that Mp is caused by a 660 kb
balanced inversion on chromosome 18 producing reciprocal 3-prime gene fusion
events involving Fbn2 and Isoc1. The Isoc1-Fbn2 fusion gene (Isoc1(Mp)) mRNA has
a frameshift and early stop codon resulting in nonsense mediated decay.
Homozygous deletions of Isoc1 do not support a significant developmental role for
this gene. The Fbn2-Isoc1 fusion gene (Fbn2 (Mp)) predicted protein consists of
the N-terminal Fibrillin-2 (amino acids 1-2646, exons 1-62) lacking the C
terminal furin-cleavage site with a short out-of-frame extension encoded by the
final exon of Isoc1. The Mp limb phenotype is consistent with that reported in
Fbn2 null embryos. However, severe eye malformations, a defining feature of Mp,
are not seen in Fbn2 null animals. Fibrillin-2(Mp) forms large fibrillar
structures within the rough endoplasmic reticulum (rER) associated with an
unfolded protein response and quantitative mass spectrometry shows a generalised
defect in protein secretion in conditioned media from mutant cells. In the
embryonic eye Fbn2 is expressed within the peripheral ciliary margin (CM). Mp
embryos show reduced canonical Wnt-signalling in the CM - known to be essential
for ciliary body development - and show subsequent aplasia of CM-derived
structures. We propose that the Mp "worse-than-null" eye phenotype plausibly
results from a failure in normal trafficking of proteins that are co-expressed
with Fbn2 within the CM. The prediction of similar trans-acting protein effects
will be an important challenge in the medical interpretation of human mutations
from whole exome sequencing.
PMID- 24348271
TI - Dual regulation of gene expression mediated by extended MAPK activation and
salicylic acid contributes to robust innate immunity in Arabidopsis thaliana.
AB - Network robustness is a crucial property of the plant immune signaling network
because pathogens are under a strong selection pressure to perturb plant network
components to dampen plant immune responses. Nevertheless, modulation of network
robustness is an area of network biology that has rarely been explored. While two
modes of plant immunity, Effector-Triggered Immunity (ETI) and Pattern-Triggered
Immunity (PTI), extensively share signaling machinery, the network output is much
more robust against perturbations during ETI than PTI, suggesting modulation of
network robustness. Here, we report a molecular mechanism underlying the
modulation of the network robustness in Arabidopsis thaliana. The salicylic acid
(SA) signaling sector regulates a major portion of the plant immune response and
is important in immunity against biotrophic and hemibiotrophic pathogens. In
Arabidopsis, SA signaling was required for the proper regulation of the vast
majority of SA-responsive genes during PTI. However, during ETI, regulation of
most SA-responsive genes, including the canonical SA marker gene PR1, could be
controlled by SA-independent mechanisms as well as by SA. The activation of the
two immune-related MAPKs, MPK3 and MPK6, persisted for several hours during ETI
but less than one hour during PTI. Sustained MAPK activation was sufficient to
confer SA-independent regulation of most SA-responsive genes. Furthermore, the
MPK3 and SA signaling sectors were compensatory to each other for inhibition of
bacterial growth as well as for PR1 expression during ETI. These results indicate
that the duration of the MAPK activation is a critical determinant for modulation
of robustness of the immune signaling network. Our findings with the plant immune
signaling network imply that the robustness level of a biological network can be
modulated by the activities of network components.
PMID- 24348272
TI - Histone methylation restrains the expression of subtype-specific genes during
terminal neuronal differentiation in Caenorhabditis elegans.
AB - Although epigenetic control of stem cell fate choice is well established, little
is known about epigenetic regulation of terminal neuronal differentiation. We
found that some differences among the subtypes of Caenorhabditis elegans VC
neurons, particularly the expression of the transcription factor gene unc-4,
require histone modification, most likely H3K9 methylation. An EGF signal from
the vulva alleviated the epigenetic repression of unc-4 in vulval VC neurons but
not the more distant nonvulval VC cells, which kept unc-4 silenced. Loss of the
H3K9 methyltransferase MET-2 or H3K9me2/3 binding proteins HPL-2 and LIN-61 or a
novel chromodomain protein CEC-3 caused ectopic unc-4 expression in all VC
neurons. Downstream of the EGF signaling in vulval VC neurons, the transcription
factor LIN-11 and histone demethylases removed the suppressive histone marks and
derepressed unc-4. Behaviorally, expression of UNC-4 in all the VC neurons caused
an imbalance in the egg-laying circuit. Thus, epigenetic mechanisms help
establish subtype-specific gene expression, which are needed for optimal activity
of a neural circuit.
PMID- 24348273
TI - Ethylene promotes hypocotyl growth and HY5 degradation by enhancing the movement
of COP1 to the nucleus in the light.
AB - In the dark, etiolated seedlings display a long hypocotyl, the growth of which is
rapidly inhibited when the seedlings are exposed to light. In contrast, the
phytohormone ethylene prevents hypocotyl elongation in the dark but enhances its
growth in the light. However, the mechanism by which light and ethylene
signalling oppositely affect this process at the protein level is unclear. Here,
we report that ethylene enhances the movement of constitutive photomorphogenesis
1 (COP1) to the nucleus where it mediates the degradation of long hypocotyl 5
(HY5), contributing to hypocotyl growth in the light. Our results indicate that
HY5 is required for ethylene-promoted hypocotyl growth in the light, but not in
the dark. Using genetic and biochemical analyses, we found that HY5 functions
downstream of ethylene insensitive 3 (EIN3) for ethylene-promoted hypocotyl
growth. Furthermore, the upstream regulation of HY5 stability by ethylene is COP1
dependent, and COP1 is genetically located downstream of EIN3, indicating that
the COP1-HY5 complex integrates light and ethylene signalling downstream of EIN3.
Importantly, the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC)
enriched the nuclear localisation of COP1; however, this effect was dependent on
EIN3 only in the presence of light, strongly suggesting that ethylene promotes
the effects of light on the movement of COP1 from the cytoplasm to the nucleus.
Thus, our investigation demonstrates that the COP1-HY5 complex is a novel
integrator that plays an essential role in ethylene-promoted hypocotyl growth in
the light.
PMID- 24348276
TI - Uptake and distribution of cd in sweet maize grown on contaminated soils: a field
scale study.
AB - Maize is an economic crop that is also a candidate for use in phytoremediation in
low-to-moderately Cd-contaminated soils, because the plant can accumulate high
concentration of Cd in parts that are nonedible to humans while accumulating only
a low concentration of Cd in the fruit. Maize cultivars CT38 and HZ were planted
in field soils contaminated with Cd and nitrilotriacetic acid (NTA) was used to
enhance the phytoextractive effect of the maize. Different organs of the plant
were analyzed to identify the Cd sinks in the maize. A distinction was made
between leaf sheath tissue and leaf lamina tissue. Cd concentrations decreased in
the tissues in the following order: sheath > root > lamina > stem > fruit. The
addition of NTA increased the amount of Cd absorbed but left the relative
distribution of the metal among the plant organs essentially unchanged. The Cd in
the fruit of maize was below the Chinese government's permitted concentration in
coarse cereals. Therefore, this study shows that it is possible to conduct maize
phytoremediation of Cd-contaminated soil while, at the same time, harvesting a
crop, for subsequent consumption.
PMID- 24348275
TI - A domesticated PiggyBac transposase interacts with heterochromatin and catalyzes
reproducible DNA elimination in Tetrahymena.
AB - The somatic genome of the ciliated protist Tetrahymena undergoes DNA elimination
of defined sequences called internal eliminated sequences (IESs), which account
for ~30% of the germline genome. During DNA elimination, IES regions are
heterochromatinized and assembled into heterochromatin bodies in the developing
somatic nucleus. The domesticated piggyBac transposase Tpb2p is essential for the
formation of heterochromatin bodies and DNA elimination. In this study, we
demonstrate that the activities of Tpb2p involved in forming heterochromatin
bodies and executing DNA elimination are genetically separable. The cysteine-rich
domain of Tpb2p, which interacts with the heterochromatin-specific histone
modifications, is necessary for both heterochromatin body formation and DNA
elimination, whereas the endonuclease activity of Tpb2p is only necessary for DNA
elimination. Furthermore, we demonstrate that the endonuclease activity of Tpb2p
in vitro and the endonuclease activity that executes DNA elimination in vivo have
similar substrate sequence preferences. These results strongly indicate that
Tpb2p is the endonuclease that directly catalyzes the excision of IESs and that
the boundaries of IESs are at least partially determined by the combination of
Tpb2p-heterochromatin interaction and relaxed sequence preference of the
endonuclease activity of Tpb2p.
PMID- 24348274
TI - The NuRD chromatin-remodeling enzyme CHD4 promotes embryonic vascular integrity
by transcriptionally regulating extracellular matrix proteolysis.
AB - The extracellular matrix (ECM) supports vascular integrity during embryonic
development. Proteolytic degradation of ECM components is required for
angiogenesis, but excessive ECM proteolysis causes blood vessel fragility and
hemorrhage. Little is understood about how ECM proteolysis is transcriptionally
regulated during embryonic vascular development. We now show that the NuRD ATP
dependent chromatin-remodeling complex promotes vascular integrity by preventing
excessive ECM proteolysis in vivo. Mice lacking endothelial CHD4--a catalytic
subunit of NuRD complexes--died at midgestation from vascular rupture. ECM
components surrounding rupture-prone vessels in Chd4 mutants were significantly
downregulated prior to embryonic lethality. Using qPCR arrays, we found two
critical mediators of ECM stability misregulated in mutant endothelial cells: the
urokinase-type plasminogen activator receptor (uPAR or Plaur) was upregulated,
and thrombospondin-1 (Thbs1) was downregulated. Chromatin immunoprecipitation
assays showed that CHD4-containing NuRD complexes directly bound the promoters of
these genes in endothelial cells. uPAR and THBS1 respectively promote and inhibit
activation of the potent ECM protease plasmin, and we detected increased plasmin
activity around rupture-prone vessels in Chd4 mutants. We rescued ECM components
and vascular rupture in Chd4 mutants by genetically reducing urokinase (uPA or
Plau), which cooperates with uPAR to activate plasmin. Our findings provide a
novel mechanism by which a chromatin-remodeling enzyme regulates ECM stability to
maintain vascular integrity during embryonic development.
PMID- 24348277
TI - Long-term effects of the Moving to Opportunity residential mobility experiment on
crime and delinquency.
AB - OBJECTIVES: Using data from a randomized experiment, to examine whether moving
youth out of areas of concentrated poverty, where a disproportionate amount of
crime occurs, prevents involvement in crime. METHODS: We draw on new
administrative data from the U.S. Department of Housing and Urban Development's
Moving to Opportunity (MTO) experiment. MTO families were randomized into an
experimental group offered a housing voucher that could only be used to move to a
low-poverty neighborhood, a Section 8 housing group offered a standard housing
voucher, and a control group. This paper focuses on MTO youth ages 15-25 in 2001
(n = 4,643) and analyzes intention to treat effects on neighborhood
characteristics and criminal behavior (number of violent- and property-crime
arrests) through 10 years after randomization. RESULTS: We find the offer of a
housing voucher generates large improvements in neighborhood conditions that
attenuate over time and initially generates substantial reductions in violent
crime arrests and sizable increases in property-crime arrests for experimental
group males. The crime effects attenuate over time along with differences in
neighborhood conditions. CONCLUSIONS: Our findings suggest that criminal behavior
is more strongly related to current neighborhood conditions (situational
neighborhood effects) than to past neighborhood conditions (developmental
neighborhood effects). The MTO design makes it difficult to determine which
specific neighborhood characteristics are most important for criminal behavior.
Our administrative data analyses could be affected by differences across areas in
the likelihood that a crime results in an arrest.
PMID- 24348278
TI - The complete targeted profile of the organic acid intermediates of the citric
acid cycle using a single stable isotope dilution analysis, sodium borodeuteride
reduction and selected ion monitoring GC/MS.
AB - The quantitative profiling of the organic acid intermediates of the citric acid
cycle (CAC) presents a challenge due to the lack of commercially available
internal standards for all of the organic acid intermediates. We developed an
analytical method that enables the quantitation of all the organic acids in the
CAC in a single stable isotope dilution GC/MS analysis with deuterium-labeled
analogs used as internal standards. The unstable alpha-keto acids are rapidly
reduced with sodium borodeuteride to the corresponding stable alpha-deutero-alpha
hydroxy acids and these, along with their unlabeled analogs and other CAC organic
acid intermediates, are converted to their tert-butyldimethylsilyl derivatives.
Selected ion monitoring is employed with electron ionization. We validated this
method by treating an untransformed mouse mammary epithelial cell line with well
known mitochondrial toxins affecting the electron transport chain and ATP
synthase, which resulted in profound perturbations of the concentration of CAC
intermediates.
PMID- 24348280
TI - Electrocautery therapy combined with oral steroid administration for refractory
corrosive esophageal stenosis prevents restenosis.
AB - A 61-year-old female with refractory corrosive esophageal stenosis repeatedly
underwent endoscopic balloon dilation at another hospital; however, no
improvements were observed in the esophageal stenosis. Consequently, she had been
on a liquid diet for the previous three years. She was admitted to our department
for further treatment. A radial incision was made, by use of the SB knife Jr, for
a pinhole-like stenosis in a short segment 39 cm from the incisor, and dilation
was safely performed by use of a CRE balloon dilator. Subsequently, prednisolone
was orally administered to prevent re-stenosis. This was followed by a favorable
clinical course.
PMID- 24348279
TI - Caregiver Burden in Fragile X Families.
AB - Complex caregiving issues occur in multigenerational families carrying the
fragile X mutation and premutation. The same family members may care for children
or siblings with fragile X syndrome (FXS) and for elderly parents with fragile X
associated tremor/ataxia syndrome (FXTAS). Family caregivers experience anxiety,
depression, neglect of personal health care needs, employment difficulties, and
loss of social support, leading to isolation and further psychiatric
consequences. There is growing awareness of caregiver burden with regard to
parents of children with FXS, but much less is known about the needs of informal
caregivers of patients with FXTAS. In this paper, we review the available
literature to date and provide suggestions for further exploration of caregivers'
needs. Evidence-based strategies to address these needs are included. Many more
research studies exploring caregiver burden in multigenerational fragile X
families are needed, as well as studies aimed at investigating interventions and
their impact on reduction.
PMID- 24348281
TI - Society for microbial ecology, microbial ecology in health and disease, and the
future.
PMID- 24348282
TI - Impact factor went on a ventilator: Neither died nor buried.
PMID- 24348283
TI - Tranexamic acid in obstetrics: Encouraging data in anemic parturients.
PMID- 24348284
TI - A survey of the practice of regional anesthesia in Saudi Arabia.
AB - OBJECTIVE: This survey aimed to assess both the extent of practice and need for
training in regional anesthesia among anesthesiologists in Saudi Arabia in 2012.
METHODS: We distributed an electronic survey among 382 anesthesiologists
attending the bi-annual meetings of the Saudi Anesthetic Association, enquiring
about their practice in regional anesthesia. Questions concerned the practice of
regional anesthesia, use of ultrasound guidance, and the need for training
workshops. RESULTS: The response rate of anesthetists was 55.2% with most of them
were males and had mean age of 25-50 years. Most anesthesiologists (88.2%) were
practicing regional anesthesia frequently in the operating rooms (75.3%) rather
than designated block room. From the respondents, only 14.2% did fellowship in
regional anesthesia, 21.8% and 18.5% were using ultrasound and nerve stimulation
guidance, respectively, 11.4% received formal training, and 86.3% were willing to
attend training workshops on regional anesthesia. There was a significant
negative correlation between the ultrasound users and their institutional
positions (r=-0.191) (P=0.026). CONCLUSIONS: We believe that more could be done
to improve the practice of regional anesthesia in the Kingdom of Saudi Arabia,
including the implementation of formal training and conduction of more frequent
specialized courses/workshops in the field of regional anesthesia with special
reference to ultrasound regional anesthesia blockade techniques.
PMID- 24348285
TI - Clinical expertise in regional anesthesia: Anesthesiologists voice their need for
formal training.
PMID- 24348286
TI - Paravertebral block can attenuate cytokine response when it replaces general
anesthesia for cancer breast surgeries.
AB - CONTEXT: Cytokine release is a well-known response to surgery especially when it
is linked to cancer. Paravertebral block (PVB) is the suitable regional
anesthesia for breast surgery. AIM: We tested the effect of replacing general
anesthesia (GA) with PVB on cytokine response during and after surgeries for
cancer breast. SETTINGS AND DESIGN: Controlled randomized study. METHODS: Forty
cancer breast patients were divided in two groups; Group I received PVB and Group
II received GA during performance of unilateral breast surgery without axillary
clearance. Plasma concentrations of interleukin (IL)-6, IL-10, IL-12 and
interferon-gamma (IFN-gamma) were measured and IL-10/IFN-gamma were estimated in
the following points; before starting PVB in Group I or induction of GA in Group
II (Sample A), before skin incision (Sample B), at the end of procedure before
shifting out of operating room (Sample C), 4-h post-operatively (Sample D) and 24
h post-operatively (Sample E). STATISTICAL ANALYSIS: unpaired Student t-test.
RESULTS: IL-6 increased progressively in both groups with statistically
significant lower levels in samples C and D in Group I. IL-10 levels showed
progressive increasing in both groups without differences between groups. IL-12
showed progressive decrease in both groups with statistically significant higher
levels in samples C and D in Group I. IFN-levels showed significantly higher
levels in samples C and D in Group I. IL-10/IFN-gamma ratio was significantly
lower in Group II in samples C and D. CONCLUSION: Replacing GA with PVB can
attenuate cytokines response to cancer breast surgeries.
PMID- 24348288
TI - Nonopioid versus opioid based general anesthesia technique for bariatric surgery:
A randomized double-blind study.
AB - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
giving general anesthesia without the use of any opioids either systemic or
intraperitoneal in bariatric surgery. METHODS: Prospective randomized controlled
trial. Obese patients (body mass index >50 Kg/m(2)) undergoing laparoscopic
sleeve gastrectomies were recruited and provided an informed signed consent.
Patients were randomized using a computer generated randomization table to
receive either opioid or non-opioid based anesthesia. The patient and the
investigator scoring patient outcome after surgery were blinded to the anesthetic
protocol. Primary outcomes were hemodynamics in the form of "heart rate,
systolic, diastolic, and mean arterial blood pressure" on induction and 1/2
hourly thereafter. Pain monitoring through visual analog scale (VAS) 30 min after
recovery, hourly for 2 h and every 4 h for 24 h was also recorded. Pain
monitoring through VAS and post-operative nausea and vomiting 30 min after
recovery were also recorded and finally patient satisfaction and acute pain nurse
satisfaction. RESULTS: There was no difference in background characteristics in
both groups. There were no statistically significant differences in different
outcomes as heart rate, mean blood pressure, O2 saturation in different timings
between groups at any of the determined eight time points but pain score and
nurse satisfaction showed a trend to better performance with non-opioid
treatment. CONCLUSION: Nonopioid based general anesthesia for Bariatric surgery
is as effective as opioid one. There is no need to use opioids for such surgery
especially that there was a trend to less pain in non-opioid anesthesia.
PMID- 24348287
TI - Transoesophageal Doppler compared to central venous pressure for perioperative
hemodynamic monitoring and fluid guidance in liver resection.
AB - PURPOSE: Major hepatic resections may result in hemodynamic changes. Aim is to
study transesophageal Doppler (TED) monitoring and fluid management in comparison
to central venous pressure (CVP) monitoring. A follow-up comparative hospital
based study. METHODS: 59 consecutive cirrhotic patients (CHILD A) undergoing
major hepatotomy. CVP monitoring only (CVP group), (n=30) and TED (Doppler
group), (n=29) with CVP transduced but not available on the monitor. Exclusion
criteria include contra-indication for Doppler probe insertion or bleeding
tendency. An attempt to reduce CVP during the resection in both groups with
colloid restriction, but crystalloids infusion of 6 ml/kg/h was allowed to
replace insensible loss. Post-resection colloids infusion were CVP guided in CVP
group (5-10 mmHg) and corrected flow time (FTc) aortic guided in Doppler group
(>0.4 s) blood products given according to the laboratory data. RESULTS: Using
the FTc to guide Hydroxyethyl starch 130/0.4 significantly decreased intake in
TED versus CVP (1.03 [0.49] versus 1.74 [0.41] Liter; P<0.05). Nausea, vomiting,
and chest infection were less in TED with a shorter hospital stay (P<0.05). No
correlation between FTc and CVP (r=0.24, P > 0.05). Cardiac index and stroke
volume of TED increased post-resection compared to baseline, 3.0 (0.9) versus 3.6
(0.9) L/min/m(2), P<0.05; 67.1 (14.5) versus 76 (13.2) ml, P<0.05, respectively,
associated with a decrease in systemic vascular resistance (SVR) 1142.7 (511)
versus 835.4 (190.9) dynes.s/cm(5), P<0.05. No significant difference in arterial
pressure and CVP between groups at any stage. CVP during resection in TED 6.4
(3.06) mmHg versus 6.1 (1.4) in CVP group, P=0.6. TED placement consumed less
time than CVP (7.3 [1.5] min versus 13.2 [2.9], P<0.05). CONCLUSION: TED in
comparison to the CVP monitoring was able to reduced colloids administration post
resection, lower morbidity and shorten hospital stay. TED consumed less time to
insert and was also able to present significant hemodynamic changes. Advanced
surgical techniques of resection play a key role in reducing blood loss despite
CVP more than 5 cm H2O. TED fluid management protocols during resection need to
be developed.
PMID- 24348289
TI - The effect of ketamine versus fentanyl on the incidence of emergence agitation
after sevoflurane anesthesia in pediatric patients undergoing tonsillectomy with
or without adenoidectomy.
AB - BACKGROUND: Emergence agitation (EA) has been documented as a common side-effect
of sevoflurane anesthesia. This prospective, randomized, double-blind, placebo
controlled study was designed to compare the effects of ketamine versus fentanyl,
administered 10 min before the end of surgery on the development of EA. METHODS:
A total of 120 children aged 3-7 years of American Society of Anesthesiologists I
II physical status were randomly assigned to one of three equal groups receiving
either ketamine 0.5 mg/kg (Group K), fentanyl 1 MUg/kg (Group F) or saline (Group
C) at 10 min before the end of surgery. Post-operative EA was assessed with
Aono's four point scale. Recovery times, the post-operative pain and adverse
reactions were assessed. RESULTS: There was no significant difference between the
three groups regarding recovery and discharge times from post-anesthesia care
unit. The incidence of EA was significantly low in Group K and Group F (15% and
17.5%, respectively) compared to the control group (42.5%), with no significant
difference between Group K and Group F. There were no significant differences in
Children's Hospital of Eastern Ontario Pain Scale between the three groups. The
incidence of nausea or vomiting was significantly more in Group F compared to
that in other two groups. However, no complications such as somnolence, oxygen
desaturation or respiratory depression occurred during the study period and there
were no episodes of hallucinations or bad dreams in the ketamine group.
CONCLUSION: The intravenous administration of either ketamine 0.5 mg/kg or
fentanyl 1 MUg/kg before the end of surgery in sevoflurane-anesthetized children
undergoing tonsillectomy with or without adenoidectomy reduces the incidence of
post-operative agitation without delaying emergence.
PMID- 24348290
TI - Entropy-guided end-tidal desflurane concentration during living donor liver
transplantation.
AB - BACKGROUND: The three phases of living donor liver transplantation (LDLT)
represent different liver conditions. The aim is to study the required end-tidal
desflurane concentration (ET-Des) guided with entropy monitoring for the depth of
anesthesia. METHODS: After the Ethics and Research Committee approval, 40
patients were included in this prospective study. Anesthesia was maintained with
Desflurane-O2-air. State entropy (SE) and Response entropy (RE) were kept between
40 and 60. RESULTS: Age and Model for End-stage Liver Disease (MELD) score were
45+/-10 years and 15.43+/-3.92, respectively. ET-Des were significantly lower in
the anhepatic phase (2.8+/-0.4%) than in the pre-anhepatic and neohepatic phases
(3.3+/-0.3%, 3.47+/-0.3%, respectively, P<0.001). The SE and RE for pre
anhepatic, anhepatic, and neohepatic phases were (45.6+/-3.7, 47.4+/-3.2),
(44.7+/-2.1, 46.4+/-2.04), and (46.1+/-3.3, 47.9+/-3.3), respectively, with no
significant changes between the phases, P > 0.05. Total operative time was 651+/
88 minutes, and for each phase it was 276+/-11, 195+/-55, and 191+/-24 minutes,
respectively. Significant changes were found in hemoglobin g/dl and hematocrit %
between the three phases (10.28+/-1.5, 30.48+/-4.3), (9.45+/-1.34, 28.36+/-4.1),
and (8.88+/-1.1, 26.63+/-3.5), P<0.05. The heart rate and mean blood pressures
were stable despite the cardiac index demonstrated a significant reduction during
the anhepatic phase (2.99+/-0.22) when compared to the pre-anhepatic and
neohepatic phases (3.60+/-0.29) and (4.72+/-0.32), respectively, (P<0.05). There
was a significant correlation between CI and ET-Des% (r=0.604, P<0.05).
CONCLUSION: Inhalational anesthetic requirements differed from one phase to
another during LDLT, with requirements being the least during the anhepatic
phase. Monitoring of the anesthesia depth was required, to avoid excess
administration, which could compromise the hemodynamics before the critical time
of reperfusion.
PMID- 24348291
TI - Comparison of unilateral spinal and continous spinal anesthesia for hip surgery
in elderly patients.
AB - BACKGROUND: Continous spinal anesthesia (CSA) and frequently unilateral spinal
anesthesia (USpA) are usually preferred for lower extremity surgeries. In this
study, we aimed to compare the effects of these anesthetic techniques, on
hemodynamic parameters, quality of anesthesia and complications in elderly
patients undergoing hip surgeries. METHODS: Forty patients aged 65 years and
older, assigned to receive either CSA or USpA with 7.5 mg (1.5 cc) 0.5%
hyperbaric bupivacaine initially. In CSA group, additional doses of 2.5 mg
bupivacaine were applied until sensory block reach to T10. Maximum sensorial
block level, time to reach the level of T10 (defined as onset time) and to
regress to T12, hemodynamic parameters and ephedrine requirements were recorded
peroperatively and during 2 h postoperatively. RESULTS: Hemodynamic parameters,
ephedrine requirements and regression of sensory block by two levels were similar
in two groups. The onset time of anesthesia was significantly longer in USpA
group than CSA group. Neuraxial anesthesia had to be converted to general
anesthesia in 5 patients (25%) in CSA group and 1 patient (5%) in USpA group.
CONCLUSIONS: We conclude that both USpA and CSA techniques have similar effects
in elderly high risk patients. On the other hand, USpA is more preferable for
surgeries with shorter durations due to its low cost and high success rate.
PMID- 24348292
TI - Causes of tracheal re-intubation after craniotomy: A prospective study.
AB - BACKGROUND: Re-intubation of neurosurgical patients after a successful tracheal
extubation in the operating room is not uncommon. However, no prospective study
has ever addressed this concern. This study was aimed at analyzing various risk
factors of re-intubation and its effect on patient outcome. METHODS: Patients
aged between 18-60 yrs and of ASA physical status I and II undergoing elective
craniotomies over a period of two yrs were included. A standard anesthetic
technique using propofol, fentanyl, rocuronium, and isoflurane/sevoflurane was
followed, in all these patients. 'Re-intubation' was defined as the necessity of
tracheal intubation within 72 hrs of a planned extubation. Data were collected
and analyzed employing standard statistical methods. RESULTS: One thousand eight
hundred and fifty patients underwent elective craniotomy, of which 920 were
included in this study. A total of 45 (4.9%) patients required re-intubation.
Mean anesthesia duration and time of re-intubation were 6.3+/-1.8 and 24.6+/-21.9
hrs, respectively. The causes of re-intubation were neurological deterioration
(55.6%), respiratory distress (22.2%), unmanageable respiratory secretion
(13.3%), and seizures (8.9%). The most common post-operative radiological (CT
scan) finding was residual tumor and edema (68.9%). Seventy-three percent of the
re-intubated patients had satisfactory post-operative cough-reflex. The ICU and
hospital stay, and Glasgow outcome scale at discharge were not significantly
affected by different causes of re-intubation. CONCLUSION: Neurological
deterioration is the most common cause of re-intubation following elective
craniotomies owing to residual tumor and surrounding edema. A satisfactory cough
reflex may not prevent subsequent re-intubation in post-craniotomy patients.
PMID- 24348293
TI - Analyzing the effects of intra-operation video-clip display on hemodynamic and
satisfaction of patients during lumbar discectomy under spinal anesthesia.
AB - OBJECTIVE: Most neurosurgeons and anesthesiologists prefer the less invasive
intervention for most surgeries; recently, the lumbar anesthesia is more popular
method. In this study we have tried to distract the attention of the patients to
their favorite video-clip instead of their surrounding operating room background
to evaluate the hemodynamic as well as their satisfaction during the operation.
METHODS: 80 patients who were scheduled for an elective one level discectomy
under the regional spinal anesthesia enrolled in this prospective randomized
clinical trial. The patients were randomized with sealed envelope method and each
envelope was randomly assigned from this set of envelops to be either in case
group one (video group) or control groups two (no audio and video and only head
phone on their ears) group. In all patients, systolic and diastolic blood
pressure, pulse rate and SPO2 were measured and recorded in the questionnaire
charts. RESULTS: Of the 80 patients with Lumbar disk herniation, 53 patients were
male and 27 female. The mean age for all patients was 44 year. Systolic and
diastolic blood pressure at the end of surgery was significantly lower in video
group (P=0.045 and 0.004). Systolic Blood pressure differences between 3(rd) and
5(th) and the end of the surgery with minute zero was significantly less in the
video group. (P=0.025, 0.018 and 0.030). Diastolic blood pressure differences
between 3(rd) and 5(th) and the end of the surgery with minute zero was
significantly less in the video group.(P=0.051, 0.019 and 0.15). Pulse rate
differences between first, 3(rd), 5(th) and exactly before leaving the recovery
room with minute zero was significantly less in the video group. (P=0.015, 0.028,
0.030 and 0.008). CONCLUSION: According to our study, by displaying patient's
favorite video clip during the surgical intervention we could highly reduce the
patient's attention to what is happening in operating room and therefore,
decrease their anxiety and stress.
PMID- 24348294
TI - Evaluation of interadductor approach in neurolytic blockade of obturator nerve in
spastic patients.
AB - BACKGROUND: Spasticity is a syndrome associated with a persistent increase in
involuntary reflex activity of a muscle in response to stretch. Adductor muscle
spasticity is a common complication of spinal cord and brain injury. It needs to
be treated if it interferes with activities of daily living and self-care.
Obturator neurolytic blockade is one of the cost-effective therapeutic
possibilities to treat spasticity of adductor group of muscles. In this study, we
assessed the efficacy of interadductor approach in alleviating the spasticity.
METHODS: Obturator neurolysis using 8-10 ml 6% phenol was given with the guidance
of a peripheral nerve stimulator in 20 spastic patients. Technical evaluation
included number of attempted needle insertions, time to accurate location of the
nerve, depth of needle insertion, and success rate. Pain, spasticity, hip
abduction range of motion (ROM), number of spasms, gait, and hygiene were
evaluated at 1(st) hour, 24(th) hour, end of the 1(st) week, and in the 1(st),
2(nd), and 3(rd) months following the intervention. RESULTS: The success rate was
100% with mean time to accurate nerve location 4.9+/-2.06 min. Average depth of
needle insertion was 2.91+/-0.32 cm. Compared with the scores measured
immediately before the block, all studied parameters improved significantly. An
increase in the Modified Ashworth Scale values was observed in the 2(nd) and
3(rd) months, but they did not reach their initial values. CONCLUSION: The
interadductor approach proved to be accurate and fast, with a high success rate.
Phenol blockade is an efficient and cost-effective technique in patients with
adductor spasticity. It led to a decrease in spasticity and pain with an increase
in the ROM of the hip and better hygiene, with an efficacy lasting for about 3
months.
PMID- 24348295
TI - Comparative evaluation of two doses of tranexamic acid used prophylactically in
anemic parturients for lower segment cesarean section: A double-blind randomized
case control prospective trial.
AB - BACKGROUND: Postpartum hemorrhage (PPH) and anemia thereafter can be a life
threatening condition in parturients undergoing lower segment cesarean section
(LSCS), especially when anemia is present. AIM: The objective of this study was
to assess two doses of Tranexamic acid (TXA) in reducing intra operative blood
loss and incidence of PPH, in terms of both efficacy and safety profiles, when
used prophylactically. METHODS: A monocenter prospective case control double
blind randomized study was carried out on a consecutive series of 90 anemic
patients undergoing LSCS, with hemoglobin between 7-10 g percent. Three random
groups were formed. Group T1 (n=30) received 10mg/kg TXA in 20 ml of 5% dextrose
intravenously, while T2 group (n=30) received 15mg/kg. Group C (n=30) received a
placebo. Drug was administered prophylactically 20 min before skin incision.
Blood loss was measured from placental delivery up to 24 hours by method of
weight and volume. STAISTICAL ANALYSIS: To compare quantitative data between two
groups, t-test, and for more than two groups ANOVA was used. To compare the mean
for non- parametric data between two groups Mann - Whitney test was used, while
in case of more than two groups Kruskal - Wallis test was employed. Probability
(p) value was considered significant when it was 0.05 or less. RESULTS: TXA
significantly reduced blood loss in both the study groups. Mean total blood loss
was 527.17+/-88.666 ml, 376.83+/-31.961ml and 261.17+/-56.777 ml in group C, T1,
and T2 respectively. While reduction of blood loss in T1 group compared to
control group was 146.34+/-56.32ml, it was 262+/-31.51ml in T2 group. Difference
between T1 and T2 was 115.66+/-24.81ml, which was statistically significant
(P<0.05). Postoperative blood loss was insignificant in all three groups. Pre-
and post-operative hemoglobin levels differed significantly when compared to
control group. Blood transfusion was needed in two patients in the control group,
whereas no patient in groups T1 and T2 needed transfusion (P=0.02). No
significant adverse effect was seen in all the three groups. CONCLUSION: Hence,
TXA was found to be effective in reducing blood loss and transfusion in anemic
parturients undergoing LSCS. 15mg/kg dose of TXA was more efficacious than the
10mg/kg dose and without any undue increase in adverse events. Postpartum anemia
is a public health problem worldwide and TXA could prove to be a very useful drug
to prevent blood loss and transfusions in patients undergoing LSCS, especially in
the anemic subgroup.
PMID- 24348296
TI - Ultrasound-guided rectus sheath block in children with umbilical hernia: Case
series.
AB - BACKGROUND: Umbilical hernia repair, a common day-case surgery procedure in
children, is associated with a significant postoperative pain. The most popular
peripheral nerve blocks used in umbilical hernia repair are rectus sheath
infiltration and caudal block. The rectus sheath block may offer improved pain
relief following umbilical hernia repair with no undesired effects such as lower
limb motor weakness or urinary retention seen with caudal block which might delay
discharge from the hospital. Ultrasound guidance of peripheral nerve blocks has
reduced the number of complications and improved the quality of blocks. The aim
of this case series is to assess the post rectus sheath block pain relief in
pediatric patients coming for umbilical surgery. METHODS: Twenty two (22)
children (age range: 1.5-8 years) scheduled for umbilical hernia repair were
included in the study. Following the induction of general anesthesia, the
ultrasonographic anatomy of the umbilical region was studied with a 5-16 MHz 50
mm linear probe. An ultrasound-guided posterior rectus sheath block of both
rectus abdominis muscles (RMs) was performed (total of 44 punctures). An in-plain
technique using Stimuplex A insulated facet tip needle 22G 50mm. Surgical
conditions, intraoperative hemodynamic parameters, and postoperative analgesia by
means of the modified CHEOPS scale were evaluated. RESULTS: ultrasonograghic
visualization of the posterior sheath was possible in all patients. The
ultrasound guided rectus sheath blockade provided sufficient analgesia in all
children with no need for additional analgesia except for one patient who
postoperatively required morphine 0.1 mg/kg intravenously. There were no
complications. CONCLUSIONS: Ultrasound guidance enables performances of an
effective rectus sheath block for umbilical hernia. Use of the Stimuplex A
insulated facet tip needle 22G 50mm provides easy, less traumatic skin and rectus
muscle penetration and satisfactory needle visualiza.
PMID- 24348297
TI - Use of extraglottic airways in patients undergoing ambulatory laparoscopic
surgery without the need for tracheal intubation.
AB - BACKGROUND: Second generation extraglottic airway devices with gastric access and
separate breathing channels have ushered in a new era where their use is
increasingly prevalent in surgical patients who would have been traditionally
intubated for general anesthesia. New innovations like the i-gel, which is
constructed of a thermoplastic elastomer, provide an airtight seal around
patient's perilaryngeal anatomy without the inflatable cuff mechanism found in
the laryngeal mask airway supreme (LMAS). METHODS: We conducted a randomized
controlled trial comparing the LMAS with the i-gel in 70 anesthetized paralyzed
patients undergoing laparoscopic female sterilization. Our primary outcome
measure was the oropharyngeal leak pressure (OLP). We studied secondary outcomes
of successful first attempt insertion rates, time and ease of the airway and
gastric tube insertion, leak fractions and pharyngeal morbidity. RESULTS: We
found no difference in the OLP between LMAS and i-gel, 25.9 (4.2) versus 24.4
(4.3) s, P=0.153. Both devices had similar first attempt insertion rates (LMAS
94% vs. i-gel 91%) with similar ease and comparable times to achieve an effective
airway, LMAS 14.7 (2.7) versus i-gel 16.5 (9.6) s, P=0.306, although gastric tube
insertion was easier and faster for the LMAS, 7.9 (1.9) versus i-gel 14.8 (7.7)
s, P<0.005. Intraoperatively, there was a significantly greater leak fraction
with the i-gel of 0.06 (0.03) versus 0.04 (0.02) with the LMAS, P=0.013. Three
patients (8.6%) with LMAS had mild sore throat; one patient (2.9%) had mucosal
injury. No complications were documented in the i-gel group. CONCLUSIONS: Both
these extraglottic airway devices offer similar OLPs, high insertion success
rates at the first attempt with similar ease and insertion times (albeit longer
gastric tube insertion with i-gel). Both provided effective ventilation despite a
higher leak fraction with i-gel that was clinically inconsequential.
PMID- 24348298
TI - Statins and succinylcholine interaction: A cause of concern for serious muscular
damage in anesthesiology practice!
AB - Statins are being extensively used in cardiac patient throughout the globe.
Succinylcholine has been the mainstay of profound relaxation during induction and
intubation of anesthesia for almost six decades now. The interactive properties
of these drugs have been of major concern during routine anesthesiology practice
in the last few years. However, no major research trial, prospective studies or
meta-analysis are available, which can truly allay the fears of possible
potential negative synergistic interactions between these two commonly used
drugs. Whatever the evidence is available is hardly enough to support a positive
outcome and the results have been drawn from observations of only few small
studies. As a result, a continuous need among anesthesiologist fraternity is felt
to arrive at a suitable inference, which can predict definite consequences of
this synergistic interaction. The present article reviews some of the important
observations of few handful studies which were carried out to observe any
potential adverse interactions between succinylcholine and statins.
PMID- 24348299
TI - Hypoglycaemia in anesthesiology practice: Diagnostic, preventive, and management
strategies.
AB - Diabetes mellitus has emerged as one of the fastest growing non communicable
diseases worldwide. Management of diabetic patients during surgical and
critically illness is of paramount challenge to anesthesiologist and intensivist.
Among its major acute complications, hypoglycemia has been given lesser attention
as compared to other major acute complications; diabetic ketoacidosis and
hyperosmolar non ketotic coma. However, newer studies and literary evidence have
established the serious concerns of morbidity and mortality, both long- and short
term, related to hypoglycemia. basis. Invariably, diabetic patients are
encountered in our daily routine practice of anesthesia. During fasting status as
well as the perioperative period, it is hypoglycemia that is of high concern to
anesthesiologist. Management has to be based on clinical, pharmacological,
social, and psychological basis, so as to completely prevent the complications
arising from an acute episode of hypoglycemia. This review aims to highlight
various aspects of hypoglycemia and its management both from endocrine and
anesthesia perspective.
PMID- 24348300
TI - Spasticity - Pathogenesis, prevention and treatment strategies.
AB - This review of the long-term management of spasticity addresses some of the
clinical dilemmas in the management of patients with chronic disability. It is
important for clinicians to have clear objectives in patient treatment and the
available treatment strategies. The review reiterates the role of physical
treatment in the management, and thereafter the maintenance of patients with
spasticity. Spasticity is a physiological consequence of an injury to the nervous
system. It is a complex problem which can cause profound disability, alone or in
combination with the other features of an upper motor neuron syndrome, and can
give rise to significant difficulties in the process of rehabilitation. This can
be associated with profound restriction to activity and participation due to
pain, weakness, and contractures. Optimum management is dependent on an
understanding of its underlying physiology, an awareness of its natural history,
an appreciation of the impact on the patient, and a comprehensive approach to
minimizing that impact. The aim of this article is to highlight the importance,
basic approach, and management options available to the general practitioner in
such a complex condition.
PMID- 24348301
TI - Anesthetic management of a patient with Marfan syndrome and severe aortic root
dilatation undergoing cholecystectomy and partial hepatic resection.
AB - Due to high mortality associated with aortic dissection, anesthetic management of
patients with Marfan syndrome with severe aortic root dilation is a challenging
situation. We describe the anesthetic management of a patient with Marfan
syndrome with severe aortic root dilation, who required major surgery like
cholecystectomy with partial liver resection under general anesthesia. A 47-year
old female presented to pre-anesthetic clinic for cholecystectomy with partial
hepatic resection for gall bladder carcinoma. Clinical features, transthoracic
echocardiography and computed tomography of thorax supported a diagnosis of
Marfan syndrome with severely dilated aortic root. Aortic dissection in patients
with Marfan syndrome and severely dilated aortic root can be precipitated by
major hemodynamic changes under anesthesia. Careful hemodynamic monitoring and
avoidance of hemodynamic swings can prevent this life-threatening event.
PMID- 24348302
TI - Inadvertent intrathecal injection of large dose magnesium sulfate.
AB - The case is a 35-year-old man who underwent spinal anesthesia for emergency
strangulated inguinal hernia repair. About five minutes after 3 ml intrathecal
drug injection, the patient suffered respiratory distress, bradycardia,
hypotension and loss of consciousness. The patient was rapidly intubated and
crystalloid infusion and epinephrine drip were established. Thereafter, he was
admitted in intensive care unit. Search for the cause revealed us that 3 ml of
magnesium sulfate (50%) was injected mistakenly for spinal anesthesia. Two days
later, he was extubated and on the fifth day, he was discharged from the hospital
without an obvious evidence of complication.
PMID- 24348303
TI - A child with xeroderma pigmentosum for excision of basal cell carcinoma.
AB - Xeroderma pigmentosum (XP) is characterized by hypersensitivity to sunlight,
ocular involvement, and progressive neurological complications. These
manifestations are due to a cellular hypersensitivity to ultraviolet radiation
leading to a defect in repair of DNA by the process of nucleotide excision
repair. Basal cell carcinoma which is rare in children can occur with XP. Though
the XP induced changes are predominately dermatologic, pose several challenges in
anaesthetic management. Hence, we are reporting a 9-year-old child with XP
scheduled for excision of basal cell carcinoma under general anaesthesia.
PMID- 24348304
TI - Orbital exenteration under trigeminal block: An innovative method of regional
anesthesia.
AB - Orbital exenteration is a disfiguring operation involving the removal of the
entire contents of the orbit, with or without the eyelids. It is widely felt that
such extensive surgery can only be performed under general anesthesia. We report
our experience with a patient who underwent orbitalexenteration under trigeminal
block with intravenous sedation. A 68-year-old male patient was diagnosed to have
orbital cellulitis (mucormycosis), uncontrolled diabetes mellitus, ischemic heart
disease, dilated cardiomyopathy with severe left ventricular systolic dysfunction
with severe pulmonary artery hypertension, and nephropathy. We decided to avoid
general anesthesia for such a high-risk patient with many co-morbid illnesses. We
gave trigeminal block using a 22-G spinal needle with local anesthetic solution
of bupivacaine 0.5% by classic approach. A standard exenteration was performed
and the patient tolerated the procedure well with no complications.
PMID- 24348305
TI - Henna dye: A cause of erroneous pulse oximetry readings.
AB - Pulse oximetry is a noninvasive and continuous monitoring of the pulsed
saturation of hemoglobin oxygen. Because of its simplicity and usefulness, it is
part of monitoring recommended for any anesthesia in the operating room.
Different factors may limit the use of this monitoring. We report a case of
difficulty monitoring by the presence of henna in a patient scheduled for general
anesthesia in prone position.
PMID- 24348306
TI - Is ketamine-propofol mixture (ketofol) an appropriate alternative induction agent
for electroconvulsive therapy?
PMID- 24348307
TI - Qualitative research in anesthesiology: An essential practice and need of the
hour.
PMID- 24348308
TI - Hemodynamically unstable atrial fibrillation after oral contrast dye instillation
in a case of Boerhaave's syndrome.
PMID- 24348309
TI - Anesthesia for a patient with thrombocytosis.
PMID- 24348310
TI - Abnormal CVP waveform.
PMID- 24348311
TI - Bifid uvula: Anesthetist don't take it lightly!
PMID- 24348312
TI - Methanol toxicity following esmolol infusion in a post-operative case of
pheochromocytoma resection.
PMID- 24348313
TI - Anesthesia for feeding jejunostomy in a case of difficult airway: A novel
approach.
PMID- 24348314
TI - Intra-arterial induction for emergency intubation-Should we use?
PMID- 24348315
TI - High altitude cerebral edema with a fatal outcome within 24 h of its onset: Shall
acclimatization be made compulsory?
PMID- 24348316
TI - Airway management for oral surgery in a patient with repaired cleft palate.
PMID- 24348317
TI - Unethical practices in anesthetic research and publication: Clinical impact,
consequences and preventive measures.
PMID- 24348318
TI - Breathing circuit obstruction: An unusual case.
PMID- 24348319
TI - Life-Threatening Gastrointestinal Mucosal Necrosis during Methotrexate Treatment
for Rheumatoid Arthritis.
AB - Methotrexate (MTX), a folic acid antagonist, is widely used in the treatment of
neoplasms, psoriasis and rheumatoid arthritis. Despite its efficacy, MTX
sometimes finds limited application because of its adverse effects, including
renal or liver impairment, bone marrow toxicity and gastrointestinal mucosal
injury. Intestinal mucositis, bleeding and peptic ulcers are well-known
gastrointestinal adverse effects of MTX, although cases of fatal mucosal necrosis
induced by MTX are extremely rare. Here, we report the case of an 82-year-old
Japanese woman who developed severe gastrointestinal mucosal necrosis after 8
years of treatment with low-dose MTX (8 mg/week). In the drug lymphocyte
stimulation test, MTX showed a strong positive reaction, with a stimulation index
of 443% against normal controls. Physicians must be aware of potential drug
induced adverse effects in patients with chronic diseases who are on long-term
medication.
PMID- 24348320
TI - Systemic Reactive Amyloidosis Associated with Castleman's Disease.
AB - We report this case of secondary amyloidosis associated with Castleman's disease.
A 51-year-old man presented with systemic symptoms of generalized weakness,
fatigue, unintended weight loss, anorexia and progressively worsening abdominal
distension. On examination he was found to have an indurated right-sided
submandibular mass and tense ascites. He was found to have multiorgan dysfunction
with deranged liver function tests and renal failure. Ascitic fluid analysis
revealed evidence of spontaneous bacterial peritonitis. Biopsy of the
submandibular mass revealed angiofollicular lymph node hyperplasia consistent
with a diagnosis of Castleman's disease. A subsequent liver biopsy showed
extensive deposition of amyloid protein. Bone marrow biopsy also showed the
presence of amyloid and increased kappa light chain-restricted plasma cells. The
patient was not considered a candidate for chemotherapy or solid organ
transplantation in view of active sepsis and poor physical condition. Secondary
systemic amyloidosis complicating Castleman's disease is very rare. Untreated
secondary systemic amyloidosis often has a rapidly fatal course, such as seen in
our patient.
PMID- 24348321
TI - Fusobacterium liver abscess.
AB - Fusobacterium is well characterized as an oropharyngeal pathogen that may induce
a septic thrombophlebitis by direct extension of abscess into an adjacent neck
vessel (Lemierre's syndrome); its potential for visceral abscess formation,
however, remains under-recognized. A 65-year-old man with a recent history of
multiple rim-enhancing liver lesions presented to the emergency room with fever
and abdominal pain. Based on interval increase in the size of the lesions,
abscess was suspected. A liver biopsy was performed, and although no organism
could be identified on routine microscopy, Warthin-Starry stain revealed Gram
negative bacilli consistent with an anaerobic Fusobacterium species as the
underlying etiology of liver abscess formation. Subsequent anaerobic culture
results confirmed the diagnosis. This case highlights the importance of
consideration for Fusobacterium infection in the setting of liver abscess if
anaerobic organisms have not yet been excluded on initial culture evaluation.
PMID- 24348322
TI - Coil migration after transarterial coil embolization of a splenic artery
pseudoaneurysm.
AB - A 48-year-old man with a history of splenic artery pseudoaneurysm requiring
transarterial embolization 3 months earlier presented to the emergency department
with abdominal pain and fever. Computed tomography showed evidence of
embolization coil fragments within the gastrointestinal tract. Upper endoscopy
showed a large gastric ulcer with numerous embolization coils extruding into the
gastric lumen. The patient underwent partial gastrectomy, distal pancreatectomy
and resection of the splenic artery pseudoaneurysm. This case illustrates a rare
delayed complication of transarterial embolization of a splenic artery
pseudoaneurysm.
PMID- 24348323
TI - The relationship between the age of onset of musical training and rhythm
synchronization performance: validation of sensitive period effects.
AB - A sensitive period associated with musical training has been proposed, suggesting
the influence of musical training on the brain and behavior is strongest during
the early years of childhood. Experiments from our laboratory have directly
tested the sensitive period hypothesis for musical training by comparing
musicians who began their training prior to age seven with those who began their
training after age seven, while matching the two groups in terms of musical
experience (Watanabe et al., 2007; Bailey and Penhune, 2010, 2012). Using this
matching paradigm, the early-trained groups have demonstrated enhanced
sensorimotor synchronization skills and associated differences in brain structure
(Bailey et al., 2013; Steele et al., 2013). The current study takes a different
approach to investigating the sensitive period hypothesis for musical training by
examining a single large group of unmatched musicians (N = 77) and exploring the
relationship between age of onset of musical training as a continuous variable
and performance on the Rhythm Synchronization Task (RST), a previously used
auditory-motor RST. Interestingly, age of onset was correlated with task
performance for those who began training earlier, however, no such relationship
was observed among those who began training in their later childhood years. In
addition, years of formal training showed a similar pattern. However, individual
working memory scores were predictive of task performance, regardless of age of
onset of musical training. Overall, these results support the sensitive period
hypothesis for musical training and suggest a non-linear relationship between age
of onset of musical training and auditory-motor rhythm synchronization abilities,
such that a relationship exists early in childhood but then plateaus later on in
development, similar to maturational growth trajectories of brain regions
implicated in playing music.
PMID- 24348324
TI - Attention effects on the processing of task-relevant and task-irrelevant speech
sounds and letters.
AB - We used event-related brain potentials (ERPs) to study effects of selective
attention on the processing of attended and unattended spoken syllables and
letters. Participants were presented with syllables randomly occurring in the
left or right ear and spoken by different voices and with a concurrent foveal
stream of consonant letters written in darker or lighter fonts. During auditory
phonological (AP) and non-phonological tasks, they responded to syllables in a
designated ear starting with a vowel and spoken by female voices, respectively.
These syllables occurred infrequently among standard syllables starting with a
consonant and spoken by male voices. During visual phonological and non
phonological tasks, they responded to consonant letters with names starting with
a vowel and to letters written in dark fonts, respectively. These letters
occurred infrequently among standard letters with names starting with a consonant
and written in light fonts. To examine genuine effects of attention and task on
ERPs not overlapped by ERPs associated with target processing or deviance
detection, these effects were studied only in ERPs to auditory and visual
standards. During selective listening to syllables in a designated ear, ERPs to
the attended syllables were negatively displaced during both phonological and non
phonological auditory tasks. Selective attention to letters elicited an early
negative displacement and a subsequent positive displacement (Pd) of ERPs to
attended letters being larger during the visual phonological than non
phonological task suggesting a higher demand for attention during the visual
phonological task. Active suppression of unattended speech during the AP and non
phonological tasks and during the visual phonological tasks was suggested by a
rejection positivity (RP) to unattended syllables. We also found evidence for
suppression of the processing of task-irrelevant visual stimuli in visual ERPs
during auditory tasks involving left-ear syllables.
PMID- 24348325
TI - Nur transcription factors in stress and addiction.
AB - The Nur transcription factors Nur77 (NGFI-B, NR4A1), Nurr1 (NR4A2), and Nor-1
(NR4A3) are a sub-family of orphan members of the nuclear receptor superfamily.
These transcription factors are products of immediate early genes, whose
expression is rapidly and transiently induced in the central nervous system by
several types of stimuli. Nur factors are present throughout the hypothalamus
pituitary-adrenal (HPA) axis where are prominently induced in response to stress.
Drugs of abuse and stress also induce the expression of Nur factors in nuclei of
the motivation/reward circuit of the brain, indicating their participation in the
process of drug addiction and in non-hypothalamic responses to stress. Repeated
use of addictive drugs and chronic stress induce long-lasting dysregulation of
the brain motivation/reward circuit due to reprogramming of gene expression and
enduring alterations in neuronal function. Here, we review the data supporting
that Nur transcription factors are key players in the molecular basis of the
dysregulation of neuronal circuits involved in chronic stress and addiction.
PMID- 24348326
TI - Small non-coding RNAs add complexity to the RNA pathogenic mechanisms in
trinucleotide repeat expansion diseases.
AB - Trinucleotide-repeat expansion diseases (TREDs) are a group of inherited human
genetic disorders normally involving late-onset neurological/neurodegenerative
affectation. Trinucleotide-repeat expansions occur in coding and non-coding
regions of unique genes that typically result in protein and RNA toxic gain of
function, respectively. In polyglutamine (polyQ) disorders caused by an expanded
CAG repeat in the coding region of specific genes, neuronal dysfunction has been
traditionally linked to the long polyQ stretch. However, a number of evidences
suggest a detrimental role of the expanded/mutant mRNA, which may contribute to
cell function impairment. In this review we describe the mechanisms of RNA
induced toxicity in TREDs with special focus in small-non-coding RNA pathogenic
mechanisms and we summarize and comment on translational approaches targeting the
expanded trinucleotide-repeat for disease modifying therapies.
PMID- 24348328
TI - Comparative functional expression of nAChR subtypes in rodent DRG neurons.
AB - We investigated the functional expression of nicotinic acetylcholine receptors
(nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal
root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it
is possible to investigate the functional expression of multiple receptor and ion
channel subtypes across more than 100 neuronal and glial cells simultaneously.
Based on nAChR expression, DRG neurons could be divided into four subclasses: (1)
neurons that express predominantly alpha3beta4 and alpha6beta4 nAChRs; (2)
neurons that express predominantly alpha7 nAChRs; (3) neurons that express a
combination of alpha3beta4/alpha6beta4 and alpha7 nAChRs; and (4) neurons that do
not express nAChRs. In this comparative study, the same four neuronal subclasses
were observed in mouse and rat DRG. However, the expression frequency differed
between species: substantially more rat DRG neurons were in the first three
subclasses than mouse DRG neurons, at all developmental time points tested in our
study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in
contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated
functional coupling between nAChRs, voltage-gated calcium channels, and
mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast
to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non
neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs.
The general approach to comparative cellular neurobiology outlined in this paper
has the potential to better integrate molecular and systems neuroscience by
uncovering the spectrum of neuronal subclasses present in a given cell population
and the functionally integrated signaling components expressed in each subclass.
PMID- 24348327
TI - Wnts in adult brain: from synaptic plasticity to cognitive deficiencies.
AB - During development of the central nervous system the Wnt signaling pathway has
been implicated in a wide spectrum of physiological processes, including neuronal
connectivity and synapse formation. Wnt proteins and components of the Wnt
pathway are expressed in the brain since early development to the adult life,
however, little is known about its role in mature synapses. Here, we review
evidences indicating that Wnt proteins participate in the remodeling of pre- and
post-synaptic regions, thus modulating synaptic function. We include the most
recent data in the literature showing that Wnts are constantly released in the
brain to maintain the basal neural activity. Also, we review the evidences that
involve components of the Wnt pathway in the development of neurological and
mental disorders, including a special emphasis on in vivo studies that relate
behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include
the evidences that support a neuroprotective role of Wnt proteins in Alzheimer's
disease. We postulate that deregulation in Wnt signaling might have a fundamental
role in the origin of neurological diseases, by altering the synaptic function at
stages where the phenotype is not yet established but when the cognitive decline
starts.
PMID- 24348330
TI - Four-dimensional multi-site photolysis of caged neurotransmitters.
AB - Neurons receive thousands of synaptic inputs that are distributed in space and
time. The systematic study of how neurons process these inputs requires a
technique to stimulate multiple yet highly targeted points of interest along the
neuron's dendritic tree. Three-dimensional multi-focal patterns produced via
holographic projection combined with two-photon photolysis of caged compounds can
provide for highly localized release of neurotransmitters within each diffraction
limited focus, and in this way emulate simultaneous synaptic inputs to the
neuron. However, this technique so far cannot achieve time-dependent stimulation
patterns due to fundamental limitations of the hologram-encoding device and other
factors that affect the consistency of controlled synaptic stimulation. Here, we
report an advanced technique that enables the design and application of arbitrary
spatio-temporal photostimulation patterns that resemble physiological synaptic
inputs. By combining holographic projection with a programmable high-speed light
switching array, we have overcome temporal limitations with holographic
projection, allowing us to mimic distributed activation of synaptic inputs
leading to action potential generation. Our experiments uniquely demonstrate
multi-site two-photon glutamate uncaging in three dimensions with submillisecond
temporal resolution. Implementing this approach opens up new prospects for
studying neuronal synaptic integration in four dimensions.
PMID- 24348329
TI - Signal processing by T-type calcium channel interactions in the cerebellum.
AB - T-type calcium channels of the Cav3 family are unique among voltage-gated calcium
channels due to their low activation voltage, rapid inactivation, and small
single channel conductance. These special properties allow Cav3 calcium channels
to regulate neuronal processing in the subthreshold voltage range. Here, we
review two different subthreshold ion channel interactions involving Cav3
channels and explore the ability of these interactions to expand the functional
roles of Cav3 channels. In cerebellar Purkinje cells, Cav3 and intermediate
conductance calcium-activated potassium (IKCa) channels form a novel complex
which creates a low voltage-activated, transient outward current capable of
suppressing temporal summation of excitatory postsynaptic potentials (EPSPs). In
large diameter neurons of the deep cerebellar nuclei, Cav3-mediated calcium
current (I T) and hyperpolarization-activated cation current (I H) are activated
during trains of inhibitory postsynaptic potentials. These currents have
distinct, and yet synergistic, roles in the subthreshold domain with I T
generating a rebound burst and I H controlling first spike latency and rebound
spike precision. However, by shortening the membrane time constant the membrane
returns towards resting value at a faster rate, allowing I H to increase the
efficacy of I T and increase the range of burst frequencies that can be
generated. The net effect of Cav3 channels thus depends on the channels with
which they are paired. When expressed in a complex with a KCa channel, Cav3
channels reduce excitability when processing excitatory inputs. If functionally
coupled with an HCN channel, the depolarizing effect of Cav3 channels is
accentuated, allowing for efficient inversion of inhibitory inputs to generate a
rebound burst output. Therefore, signal processing relies not only on the
activity of individual subtypes of channels but also on complex interactions
between ion channels whether based on a physical complex or by indirect effects
on membrane properties.
PMID- 24348332
TI - Mapping the pathophysiology of schizophrenia: interactions between multiple
cellular pathways.
PMID- 24348331
TI - Enhancement of ventricular-subventricular zone-derived neurogenesis and
oligodendrogenesis by erythropoietin and its derivatives.
AB - In the postnatal mammalian brain, stem cells in the ventricular-subventricular
zone (V-SVZ) continuously generate neuronal and glial cells throughout life.
Genetic labeling of cells of specific lineages have demonstrated that the V-SVZ
is an important source of the neuroblasts and/or oligodendrocyte progenitor cells
(OPCs) that migrate toward injured brain areas in response to several types of
insult, including ischemia and demyelinating diseases. However, this spontaneous
regeneration is insufficient for complete structural and functional restoration
of the injured brain, so interventions to enhance these processes are sought for
clinical applications. Erythropoietin (EPO), a clinically applied erythropoietic
factor, is reported to have cytoprotective effects in various kinds of insult in
the central nervous system. Moreover, recent studies suggest that EPO promotes
the V-SVZ-derived neurogenesis and oligodendrogenesis. EPO increases the
proliferation of progenitors in the V-SVZ and/or the migration and
differentiation of their progenies in and around injured areas, depending on the
dosage, timing, and duration of treatment, as well as the type of animal model
used. On the other hand, EPO has undesirable side effects, including thrombotic
complications. We recently demonstrated that a 2-week treatment with the EPO
derivative asialo-EPO promotes the differentiation of V-SVZ-derived OPCs into
myelin-forming mature oligodendrocytes in the injured white matter of neonatal
mice without causing erythropoiesis. Here we present an overview of the
multifaceted effects of EPO and its derivatives in the V-SVZ and discuss the
possible applications of these molecules in regenerative medicine.
PMID- 24348333
TI - Characterization of Wnt/beta-catenin and BMP/Smad signaling pathways in an in
vitro model of amyotrophic lateral sclerosis.
AB - Different pathways activated by morphogens of the early embryonic development,
such as the Wnt and the Bone Morphogenetic Protein (BMP) ligands, are involved in
diverse physiological and pathological conditions of the nervous system,
including neurodegeneration. In this work, we have analyzed the endogenous
activity of the canonical Wnt/beta-catenin and BMP/Smad-dependent pathways in an
in vitro model of amyotrophic lateral sclerosis (ALS), given by motor neuron-like
NSC34 cells stably expressing wild-type or G93A mutated forms of human Cu/Zn
superoxide dismutase-1 (SOD1). As ALS-derived motor neurons, NSC34 cells
expressing mutated hSOD1 show a decreased proliferation rate, are more
susceptible to oxidation-induced cell death and display Golgi fragmentation. In
addition, they display an impaired ability to induce the expression of the motor
neuronal marker Hb9 and, consistently, to morphologically differentiate into a
motor neuronal phenotype. Regarding signaling, our data show that the
transcriptional activity associated to the Wnt/beta-catenin pathway is decreased,
a finding possibly associated to the cytosolic aggregation of beta-catenin. In
turn, the BMP-dependent phosphorylation of Smad1 and the transcriptional
activation of the BMP/Smad pathway is increased in the pathologic model.
Together, these findings suggest that Wnt/beta-catenin and the BMP-dependent
pathways could play relevant roles in the neurodegeneration of motor neurons in
the context of ALS.
PMID- 24348334
TI - Redox environment is an intracellular factor to operate distinct pathways for
aggregation of Cu,Zn-superoxide dismutase in amyotrophic lateral sclerosis.
AB - Dominant mutations in Cu,Zn-superoxide dismutase (SOD1) cause a familial form of
amyotrophic lateral sclerosis (fALS). Misfolding and aggregation of mutant SOD1
proteins are a pathological hallmark of SOD1-related fALS cases; however, the
molecular mechanism of SOD1 aggregation remains controversial. Here, I have used
E. coli as a model organism and shown multiple distinct pathways of SOD1
aggregation that are dependent upon its thiol-disulfide status. Overexpression of
fALS-mutant SOD1s in the cytoplasm of E. coli BL21 and SHuffle(TM), where redox
environment is reducing and oxidizing, respectively, resulted in the formation of
insoluble aggregates with notable differences; a disulfide bond of SOD1 was
completely reduced in BL21 or abnormally formed between SOD1 molecules in
SHuffle(TM). Depending upon intracellular redox environment, therefore, mutant
SOD1 is considered to misfold/aggregate through distinct pathways, which would be
relevant in description of the pathological heterogeneity of SOD1-related fALS
cases.
PMID- 24348335
TI - Undifferentiated embryonic stem cells express ionotropic glutamate receptor
mRNAs.
AB - Ionotropic glutamate receptors (iGluRs) do not only mediate the majority of
excitatory neurotransmission in the vertebrate CNS, but also modulate pre- and
postnatal neurogenesis. Most of the studies on the developmental role of iGluRs
are performed on neural progenitors and neural stem cells (NSCs). We took a step
back in our study by examining the role of iGluRs in the earliest possible cell
type, embryonic stem cells (ESCs), by looking at the mRNA expression of the major
iGluR subfamilies in undifferentiated mouse ESCs. For that, we used two distinct
murine ES cell lines, 46C ESCs and J1 ESCs. Regarding 46C ESCs, we found
transcripts of kainate receptors (KARs) (GluK2 to GluK5), AMPA receptors (AMPARs)
(GluA1, GluA3, and GluA4), and NMDA receptors (NMDARs) (GluN1, and GluN2A to
GluN2D). Analysis of 46C-derived cells of later developmental stages, namely
neuroepithelial precursor cells (NEPs) and NSCs, revealed that the mRNA
expression of KARs is significantly upregulated in NEPs and, subsequently,
downregulated in NSCs. However, we could not detect any protein expression of any
of the KAR subunits present on the mRNA level either in ESCs, NEPs, or NSCs.
Regarding AMPARs and NMDARs, GluN2A is weakly expressed at the protein level only
in NSCs. Matching our findings for iGluRs, all three cell types were found to
weakly express pre- and postsynaptic markers of glutamatergic synapses only at
the mRNA level. Finally, we performed patch-clamp recordings of 46C ESCs and
could not detect any current upon iGluR agonist application. Similar to 46C ESCs,
J1 ESCs express KARs (GluK2 to GluK5), AMPARs (GluA3), and NMDARs (GluN1, and
GluN2A to GluN2D) at the mRNA level, but these transcripts are not translated
into receptor proteins either. Thus, we conclude that ESCs do not contain
functional iGluRs, although they do express an almost complete set of iGluR
subunit mRNAs.
PMID- 24348336
TI - A role for the canonical nuclear factor-kappaB pathway in coupling neurotrophin
induced differential survival of developing spiral ganglion neurons.
AB - Neurotrophins are key players of neural development by controlling cell death
programs. However, the signaling pathways that mediate their selective responses
in different populations of neurons remain unclear. In the mammalian cochlea,
sensory neurons differentiate perinatally into type I and II populations both
expressing TrkB and TrkC, which bind respectively brain-derived neurotrophic
factor (BDNF) and neurotrophin-3 (NT3). How these two neuronal populations
respond differentially to these two neurotrophins remains unknown. Here, we
report in rat the segregation of the nuclear factor-kappaB (NFkappaB) subunit p65
specifically within the type II population postnatally. Using dissociated
cultures of embryonic and postnatal spiral ganglion neurons, we observed a
specific requirement of NFkappaB for BDNF but not NT3-dependent neuronal survival
during a particular postnatal time window that corresponds to a period of
neuronal cell death and hair cell innervation refinement in the developing
cochlea. Consistently, postnatal p65 knockout mice showed a specific decreased
number in type II spiral ganglion neurons. Taken together, these results identify
NFkappaB as a type II neuron-specific factor that participates in the selective
survival effects of BDNF and NT3 signaling on developing spiral ganglion neurons.
PMID- 24348337
TI - Molecular mechanisms driving homeostatic plasticity of neurotransmitter release.
AB - Homeostatic plasticity is a process by which neurons adapt to the overall network
activity to keep their firing rates in a reasonable range. At the cellular level
this kind of plasticity comprises modulation of cellular excitability and tuning
of synaptic strength. In this review we concentrate on presynaptic homeostatic
plasticity controlling the efficacy of neurotransmitter release from presynaptic
boutons. While morphological and electrophysiological approaches were successful
to describe homeostatic plasticity-induced changes in the presynaptic
architecture and function, cellular and molecular mechanisms underlying those
modifications remained largely unknown for a long time. We summarize the latest
progress made in the understanding of homeostasis-induced regulation of different
steps of the synaptic vesicle cycle and the molecular machineries involved in
this process. We particularly focus on the role of presynaptic scaffolding
proteins, which functionally and spatially organize synaptic vesicle clusters,
neurotransmitter release sites and the associated endocytic machinery. These
proteins turned out to be major presynaptic substrates for remodeling during
homeostatic plasticity. Finally, we discuss cellular processes and signaling
pathways acting during homeostatic molecular remodeling and their potential
involvement in the maladaptive plasticity occurring in multiple neuropathologic
conditions such as neurodegeneration, epilepsy and neuropsychiatric disorders.
PMID- 24348338
TI - Short duration waveforms recorded extracellularly from freely moving rats are
representative of axonal activity.
AB - While extracellular somatic action potentials from freely moving rats have been
well characterized, axonal activity has not. We report direct extracellular
tetrode recordings of putative axons whose principal feature is a short duration
waveform (SDW) with an average peak-trough length less than 179 MUs. While SDW
recordings using tetrodes have previously been treated as questionable or
classified as cells, we hypothesize that they are representative of axonal
activity. These waveforms have significantly shorter duration than somatic action
potentials, are triphasic and are therefore similar to classic descriptions of
microelectrode recordings in white matter and of in vitro action potential
propagation along axons. We describe SDWs recorded from pure white-matter tracts
including the alveus and corpus callosum. Recordings of several SDWs in the
alveus exhibit grid-like firing patterns suggesting these axons carry spatial
information from entorhinal cortical neurons. Finally, we locally injected the
GABAA agonist Muscimol into layer CA1 of the hippocampus while simultaneously
recording somatic activity and SDWs on the same tetrodes. The persistent activity
of SDWs during Muscimol inactivation of somatic action potentials indicates that
SDWs are representative of action potential propagation along axons projecting
from more distal somata. This characterization is important as it illustrates the
dangers of exclusively using spike duration as the sole determinant of unit type,
particularly in the case of interneurons whose peak-trough times overlap with
SDWs. It may also allow future studies to explore how axonal projections from
disparate brain regions integrate spatial information in the hippocampus, and
provide a basis for studying the effects of pharmaceutical agents on signal
transmission in axons, and ultimately to aid in defining the potential role of
axons in cognition.
PMID- 24348339
TI - Classification of neocortical interneurons using affinity propagation.
AB - In spite of over a century of research on cortical circuits, it is still unknown
how many classes of cortical neurons exist. In fact, neuronal classification is a
difficult problem because it is unclear how to designate a neuronal cell class
and what are the best characteristics to define them. Recently, unsupervised
classifications using cluster analysis based on morphological, physiological, or
molecular characteristics, have provided quantitative and unbiased identification
of distinct neuronal subtypes, when applied to selected datasets. However, better
and more robust classification methods are needed for increasingly complex and
larger datasets. Here, we explored the use of affinity propagation, a recently
developed unsupervised classification algorithm imported from machine learning,
which gives a representative example or exemplar for each cluster. As a case
study, we applied affinity propagation to a test dataset of 337 interneurons
belonging to four subtypes, previously identified based on morphological and
physiological characteristics. We found that affinity propagation correctly
classified most of the neurons in a blind, non-supervised manner. Affinity
propagation outperformed Ward's method, a current standard clustering approach,
in classifying the neurons into 4 subtypes. Affinity propagation could therefore
be used in future studies to validly classify neurons, as a first step to help
reverse engineer neural circuits.
PMID- 24348343
TI - A perspective on terra incognita: uncovering the neuroanatomy of the human
subcortex.
AB - Recent exciting advancements in the field of in vivo neuroimaging allow for
visualization of the living human brain with unprecedented anatomical detail.
Large consortium studies will provide us with novel insights in the function and
connectivity of the human brain. However, it is unlikely that the spatial
resolution obtained using in vivo imaging will, in the near future, approximate
the level of detail obtained in post-mortem anatomical studies. Initiatives such
as the recently published Big Brain project (Amunts et al., 2013) herald a novel
approach in post-mortem brain research. We feel that linking data from
histological observations with in vivo imaging studies will greatly advance our
understanding of the functional neuroanatomy of the human brain.
PMID- 24348341
TI - Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear
glucocorticoid receptor in rat hippocampus.
AB - Modulation of synapses under acute stress is attracting much attention. Exposure
to acute stress induces corticosterone (CORT) secretion from the adrenal cortex,
resulting in rapid increase of CORT levels in plasma and the hippocampus. We
tried to test whether rapid CORT effects involve activation of essential kinases
as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the
density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat
hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are
post-synaptic regions whose presynaptic partners are mossy fiber terminals. The
application of CORT at 100, 500, and 1000 nM induced a rapid increase in the
density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co
administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished
the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC,
suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK
3beta was not involved in the signaling of thorn-genesis. Blocking AMPA receptors
suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was
demonstrated by immunogold electron microscopic analysis. From these results,
stress levels of CORT (100-1000 nM) might drive the rapid thorn-genesis via
synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear
GRs cannot be completely excluded.
PMID- 24348340
TI - Japanese studies on neural circuits and behavior of Caenorhabditis elegans.
AB - The nematode Caenorhabditis elegans is an ideal organism for studying neural
plasticity and animal behaviors. A total of 302 neurons of a C. elegans
hermaphrodite have been classified into 118 neuronal groups. This simple neural
circuit provides a solid basis for understanding the mechanisms of the brains of
higher animals, including humans. Recent studies that employ modern imaging and
manipulation techniques enable researchers to study the dynamic properties of
nervous systems with great precision. Behavioral and molecular genetic analyses
of this tiny animal have contributed greatly to the advancement of neural circuit
research. Here, we will review the recent studies on the neural circuits of C.
elegans that have been conducted in Japan. Several laboratories have established
unique and clever methods to study the underlying neuronal substrates of
behavioral regulation in C. elegans. The technological advances applied to
studies of C. elegans have allowed new approaches for the studies of complex
neural systems. Through reviewing the studies on the neuronal circuits of C.
elegans in Japan, we will analyze and discuss the directions of neural circuit
studies.
PMID- 24348342
TI - GABAergic neurons in the preoptic area send direct inhibitory projections to
orexin neurons.
AB - Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly
during sleep, exhibiting sleep/waking state-dependent firing patterns that are
the reciprocal of those observed in the arousal system. The majority of these
preoptic "sleep-active" neurons contain the inhibitory neurotransmitter GABA. On
the other hand, a population of neurons in the lateral hypothalamic area (LHA)
contains orexins, which play an important role in the maintenance of wakefulness,
and exhibit an excitatory influence on arousal-related neurons. It is important
to know the anatomical and functional interactions between the POA sleep-active
neurons and orexin neurons, both of which play important, but opposite roles in
regulation of sleep/wakefulness states. In this study, we confirmed that specific
pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase
in the amount of non-rapid eye movement (NREM) sleep. We next examined direct
connectivity between POA GABAergic neurons and orexin neurons using
channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic
tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV
mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing
axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of
orexin neurons. We found that these neurons send widespread projections to
wakefulness-related areas in the hypothalamus and brain stem, including the LHA
where these fibers make close appositions to orexin neurons. Optogenetic
stimulation of these fibers resulted in rapid inhibition of orexin neurons. These
observations suggest direct connectivity between POA GABAergic neurons and orexin
neurons.
PMID- 24348344
TI - Music and emotion-a composer's perspective.
AB - This article takes an experiential and anecdotal look at the daily lives and work
of film composers as creators of music. It endeavors to work backwards from what
practitioners of the art and craft of music do instinctively or unconsciously,
and try to shine a light on it as a conscious process. It examines the role of
the film composer in his task to convey an often complex set of emotions, and
communicate with an immediacy and universality that often sit outside of common
language. Through the experiences of the author, as well as interviews with
composer colleagues, this explores both concrete and abstract ways in which music
can bring meaning and magic to words and images, and as an underscore to our
daily lives.
PMID- 24348345
TI - Unilateral hearing during development: hemispheric specificity in plastic
reorganizations.
AB - The present study investigates the hemispheric contributions of neuronal
reorganization following early single-sided hearing (unilateral deafness). The
experiments were performed on ten cats from our colony of deaf white cats. Two
were identified in early hearing screening as unilaterally congenitally deaf. The
remaining eight were bilaterally congenitally deaf, unilaterally implanted at
different ages with a cochlear implant. Implanted animals were chronically
stimulated using a single-channel portable signal processor for two to five
months. Microelectrode recordings were performed at the primary auditory cortex
under stimulation at the hearing and deaf ear with bilateral cochlear implants.
Local field potentials (LFPs) were compared at the cortex ipsilateral and
contralateral to the hearing ear. The focus of the study was on the morphology
and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced
hemisphere-specific effects were observed. Morphology of amplitude-normalized
LFPs for stimulation of the deaf and the hearing ear was similar for responses
recorded at the same hemisphere. However, when comparisons were performed between
the hemispheres, the morphology was more dissimilar even though the same ear was
stimulated. This demonstrates hemispheric specificity of some cortical
adaptations irrespective of the ear stimulated. The results suggest a specific
adaptation process at the hemisphere ipsilateral to the hearing ear, involving
specific (down-regulated inhibitory) mechanisms not found in the contralateral
hemisphere. Finally, onset latencies revealed that the sensitive period for the
cortex ipsilateral to the hearing ear is shorter than that for the contralateral
cortex. Unilateral hearing experience leads to a functionally-asymmetric brain
with different neuronal reorganizations and different sensitive periods involved.
PMID- 24348346
TI - Decomposition of abnormal free locomotor behavior in a rat model of Parkinson's
disease.
AB - Poverty of spontaneous movement, slowed execution and reduced amplitudes of
movement (akinesia, brady- and hypokinesia) are cardinal motor manifestations of
Parkinson's disease that can be modeled in experimental animals by brain lesions
affecting midbrain dopaminergic neurons. Most behavioral investigations in
experimental parkinsonism have employed short-term observation windows to assess
motor impairments. We postulated that an analysis of longer-term free exploratory
behavior could provide further insights into the complex fine structure of
altered locomotor activity in parkinsonian animals. To this end, we video
monitored 23 h of free locomotor behavior and extracted several behavioral
measures before and after the expression of a severe parkinsonian phenotype
following bilateral 6-hydroxydopamine (6-OHDA) lesions of the rat dopaminergic
substantia nigra. Unbiased stereological cell counting verified the degree of
midbrain tyrosine hydroxylase positive cell loss in the substantia nigra and
ventral tegmental area. In line with previous reports, overall covered distance
and maximal motion speed of lesioned animals were found to be significantly
reduced compared to controls. Before lesion surgery, exploratory rat behavior
exhibited a bimodal distribution of maximal speed values obtained for single
movement episodes, corresponding to a "first" and "second gear" of motion. 6-OHDA
injections significantly reduced the incidence of second gear motion episodes and
also resulted in an abnormal prolongation of these fast motion events. Likewise,
the spatial spread of such episodes was increased in 6-OHDA rats. The increase in
curvature of motion tracks was increased in both lesioned and control animals. We
conclude that the discrimination of distinct modes of motion by statistical
decomposition of longer-term spontaneous locomotion provides useful insights into
the fine structure of fluctuating motor functions in a rat analog of Parkinson's
disease.
PMID- 24348347
TI - Training changes processing of speech cues in older adults with hearing loss.
AB - Aging results in a loss of sensory function, and the effects of hearing
impairment can be especially devastating due to reduced communication ability.
Older adults with hearing loss report that speech, especially in noisy
backgrounds, is uncomfortably loud yet unclear. Hearing loss results in an
unbalanced neural representation of speech: the slowly-varying envelope is
enhanced, dominating representation in the auditory pathway and perceptual
salience at the cost of the rapidly-varying fine structure. We hypothesized that
older adults with hearing loss can be trained to compensate for these changes in
central auditory processing through directed attention to behaviorally-relevant
speech sounds. To that end, we evaluated the effects of auditory-cognitive
training in older adults (ages 55-79) with normal hearing and hearing loss. After
training, the auditory training group with hearing loss experienced a reduction
in the neural representation of the speech envelope presented in noise,
approaching levels observed in normal hearing older adults. No changes were noted
in the control group. Importantly, changes in speech processing were accompanied
by improvements in speech perception. Thus, central processing deficits
associated with hearing loss may be partially remediated with training, resulting
in real-life benefits for everyday communication.
PMID- 24348348
TI - Harnessing electric potential: DLPFC tDCS induces widespread brain perfusion
changes.
PMID- 24348349
TI - Valproate reopens critical-period learning of absolute pitch.
AB - Absolute pitch, the ability to identify or produce the pitch of a sound without a
reference point, has a critical period, i.e., it can only be acquired early in
life. However, research has shown that histone-deacetylase inhibitors (HDAC
inhibitors) enable adult mice to establish perceptual preferences that are
otherwise impossible to acquire after youth. In humans, we found that adult men
who took valproate (VPA) (a HDAC inhibitor) learned to identify pitch
significantly better than those taking placebo-evidence that VPA facilitated
critical-period learning in the adult human brain. Importantly, this result was
not due to a general change in cognitive function, but rather a specific effect
on a sensory task associated with a critical-period.
PMID- 24348350
TI - Stress modulates intestinal secretory immunoglobulin A.
AB - Stress is a response of the central nervous system to environmental stimuli
perceived as a threat to homeostasis. The stress response triggers the generation
of neurotransmitters and hormones from the hypothalamus pituitary adrenal axis,
sympathetic axis and brain gut axis, and in this way modulates the intestinal
immune system. The effects of psychological stress on intestinal immunity have
been investigated mostly with the restraint/immobilization rodent model,
resulting in an up or down modulation of SIgA levels depending on the intensity
and time of exposure to stress. SIgA is a protein complex formed by dimeric
(dIgA) or polymeric IgA (pIgA) and the secretory component (SC), a peptide
derived from the polymeric immunoglobulin receptor (pIgR). The latter receptor is
a transmembrane protein expressed on the basolateral side of gut epithelial
cells, where it uptakes dIgA or pIgA released by plasma cells in the lamina
propria. As a result, the IgA-pIgR complex is formed and transported by vesicles
to the apical side of epithelial cells. pIgR is then cleaved to release SIgA into
the luminal secretions of gut. Down modulation of SIgA associated with stress can
have negative repercussions on intestinal function and integrity. This can take
the form of increased adhesion of pathogenic agents to the intestinal epithelium
and/or an altered balance of inflammation leading to greater intestinal
permeability. Most studies on the molecular and biochemical mechanisms involved
in the stress response have focused on systemic immunity. The present review
analyzes the impact of stress (mostly by restraint/immobilization, but also with
mention of other models) on the generation of SIgA, pIgR and other humoral and
cellular components involved in the intestinal immune response. Insights into
these mechanisms could lead to better therapies for protecting against pathogenic
agents and avoiding epithelial tissue damage by modulating intestinal
inflammation.
PMID- 24348351
TI - Polymorphisms of the OXTR gene explain why sales professionals love to help
customers.
AB - Polymorphisms of the OXTR gene affect people's social interaction styles in
various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in
general, are more motivated to interact socially and detect social salience. We
focus on sales professionals operating in knowledge intensive organizations.
Study 1, with a sample of 141 sales people, shows that carriers of the OXTR GG
allele, compared to the OXTR AA/AG allele, are more motivated to help customers
than to manipulatively impose goods/services on them. Study 2, using genomic
functional magnetic resonance imaging (fMRI) on a sample of 21 sales
professionals processing facial pictures with different emotional valences,
investigates key nuclei of social brain regions (SBRs). Compared to OXTR AA/AG
carriers, OXTR GG carriers experience greater effective connectivity between SBRs
of interest measured by Granger causality tests using univariate Haugh tests. In
addition, the multivariate El-Himdi and Roy tests demonstrate that the amygdala,
prefrontal cortex, and pars opercularis (inferior frontal gyrus) play key roles
when processing emotional expressions. The bilateral amygdala and medial
prefrontal cortex (mPFC) show significantly greater clout-influence on other
brain regions-for GG allele carriers than non-carriers; likewise, the bilateral
pars opercularis, left amygdala, and left mPFC are more receptive to activity in
other brain regions among GG allele carriers than AG/AA allele carriers are.
Thus, carriers of the OXTR GG allele are more sensitive to changes in emotional
cues, enhancing social salience. To our knowledge, this is the first study on how
insights from imaging genetics help understanding of the social motivation of
people operating in a professional setting.
PMID- 24348352
TI - Oscillatory interaction between amygdala and hippocampus coordinates behavioral
modulation based on reward expectation.
AB - The aim of this study is to examine how the amygdala and hippocampus interact for
behavioral performance modulated by different Reward-expectations (REs). We
simultaneously recorded neuronal spikes and local field potential from the
basolateral amygdala and hippocampal CA1 while rats were performing a light-side
discrimination task with different expectations of a high or low probability of
reward delivery. Here, we report the following results. First, the rats actually
modulated their behavioral performance on their expectations of a high or low
probability of reward. Second, we found more neurons related to RE in the
amygdala and more neurons related to task performance in the hippocampus. Third,
a prominent increase in the coherence of high-frequency oscillations (HFOs) (90
150 Hz) between the amygdala and the hippocampus was present during high RE.
Fourth, coherent HFOs during inter-trial intervals and theta coherence during
trials had significant correlations with the behavioral goal-selection time.
Finally, cross-frequency couplings of LFPs within and across the amygdala and
hippocampus occurred during ITI. These results suggest that the amygdala and
hippocampus have different functional roles in the present task with different
REs, and the distinctive band of coherence between the amygdala and the
hippocampus contributes to behavioral modulation on the basis of REs. We propose
that the amygdala influences firing rates and the strength of synchronization of
hippocampal neurons through coherent oscillation, which is a part of the
mechanism of how reward expectations modulate goal-directed behavior.
PMID- 24348353
TI - Skills development in infants: a possible role for widespread neurogenesis?
PMID- 24348354
TI - Appetitive behavioral traits and stimulus intensity influence maintenance of
conditioned fear.
AB - INDIVIDUAL DIFFERENCES IN APPETITIVE LEARNING HAVE LONG BEEN REPORTED, AND
GENERALLY DIVIDE INTO TWO CLASSES OF RESPONSES: cue- vs. reward-directed. The
influence of cue- vs. reward-directed phenotypes on aversive cue processing, is
less well understood. In the current study, we first categorized rats based on
their predominant cue-directed orienting responses during appetitive Pavlovian
conditioning. Then, we investigated the effect of phenotype on the latency to
exit a familiar dark environment and enter an unfamiliar illuminated open field.
Next, we examined whether the two phenotypes responded differently to a
reconsolidation updating manipulation (retrieval+extinction) after fear
conditioning. We report that the rats with a cue-directed ("orienting") phenotype
differentially respond to the open field, and also to fear conditioning,
depending on US-intensity. In addition, our findings suggest that, regardless of
appetitive phenotype or shock intensity, extinction within the reconsolidation
window prevents spontaneous recovery of fear.
PMID- 24348355
TI - What motivates gambling behavior? Insight into dopamine's role.
PMID- 24348356
TI - GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex
are necessary for odor span in rats.
AB - Working memory is a type of short-term memory involved in the maintenance and
manipulation of information essential for complex cognition. While memory span
capacity has been extensively studied in humans as a measure of working memory,
it has received considerably less attention in rodents. Our aim was to examine
the role of the N-methyl-D-aspartate (NMDA) and alpha-Amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid (AMPA) glutamate receptors in odor span capacity using
systemic injections or infusions of receptor antagonists into the medial
prefrontal cortex (mPFC). Long Evans rats were trained on a well-characterized
odor span task (OST). Initially, rats were trained to dig for a food reward in
sand followed by training on a non-match to sample discrimination using sand
scented with household spices. The rats were then required to perform a serial
delayed non-match to sample procedure which was their odor span. Systemic
injection of the broad spectrum NMDA receptor antagonist 3-(2-Carboxypiperazin-4
yl)propyl-1-phosphonic acid (CPP) (10 mg/kg) or the GluN2B-selective antagonist
Ro 25-6981 (10 mg/kg but not 6 mg/kg) significantly reduced odor span capacity.
Infusions of the GluN2B- selective antagonist Ro 25-6981 (2.5 MUg/hemisphere)
into mPFC reduced span capacity, an effect that was nearly significant (p =
0.069). Infusions of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3
dione (CNQX) (1.25 MUg/hemisphere) into mPFC reduced span capacity and latency
for the rats to make a choice in the task. These results demonstrate span
capacity in rats depends on ionotropic glutamate receptor activation in the mPFC.
Further understanding of the circuitry underlying span capacity may aid in the
novel therapeutic drug development for persons with working memory impairments as
a result of disorders such as schizophrenia and Alzheimer's disease.
PMID- 24348357
TI - Retraction: Episodic memory: a comparative approach.
PMID- 24348359
TI - The functional anatomy of attention: a DCM study.
AB - Recent formulations of attention-in terms of predictive coding-associate
attentional gain with the expected precision of sensory information. Formal
models of the Posner paradigm suggest that validity effects can be explained in a
principled (Bayes optimal) fashion in terms of a cue-dependent setting of
precision or gain on the sensory channels reporting anticipated target locations,
which is updated selectively by invalid targets. This normative model is equipped
with a biologically plausible process theory in the form of predictive coding,
where precision is encoded by the gain of superficial pyramidal cells reporting
prediction error. We used dynamic causal modeling to assess the evidence in
magnetoencephalographic responses for cue-dependent and top-down updating of
superficial pyramidal cell gain. Bayesian model comparison suggested that it is
almost certain that differences in superficial pyramidal cells gain-and its top
down modulation-contribute to observed responses; and we could be more than 80%
certain that anticipatory effects on post-synaptic gain are limited to visual
(extrastriate) sources. These empirical results speak to the role of attention in
optimizing perceptual inference and its formulation in terms of predictive
coding.
PMID- 24348358
TI - Facets and mechanisms of adaptive pain behavior: predictive regulation and
action.
AB - Neural mechanisms underlying nociception and pain perception are considered to
serve the ultimate goal of limiting tissue damage. However, since pain usually
occurs in complex environments and situations that call for elaborate control
over behavior, simple avoidance is insufficient to explain a range of mammalian
pain responses, especially in the presence of competing goals. In this
integrative review we propose a Predictive Regulation and Action (PRA) model of
acute pain processing. It emphasizes evidence that the nervous system is
organized to anticipate potential pain and to adjust behavior before the risk of
tissue damage becomes critical. Regulatory processes occur on many levels, and
can be dynamically influenced by local interactions or by modulation from other
brain areas in the network. The PRA model centers on neural substrates supporting
the predictive nature of pain processing, as well as on finely-calibrated yet
versatile regulatory processes that ultimately affect behavior. We outline
several operational categories of pain behavior, from spinally-mediated reflexes
to adaptive voluntary action, situated at various neural levels. An implication
is that neural processes that track potential tissue damage in terms of
behavioral consequences are an integral part of pain perception.
PMID- 24348360
TI - Navigating the complex path between the oxytocin receptor gene (OXTR) and
cooperation: an endophenotype approach.
AB - Although cooperation represents a core facet of human social behavior there
exists considerable variability across people in terms of the tendency to
cooperate. One factor that may contribute to individual differences in
cooperation is a key gene within the oxytocin (OT) system, the OT reception gene
(OXTR). In this article, we aim to bridge the gap between the OXTR gene and
cooperation by using an endophenotype approach. We present evidence that the
association between the OXTR gene and cooperation may in part be due to how the
OXTR gene affects brain systems involved in emotion recognition, empathy/theory
of mind, social communication and social reward seeking. There is evidence that
the OXTR gene is associated with the functional anatomy of the amygdala, visual
cortex (VC), anterior cingulate and superior temporal gyrus (STG). However, it is
currently unknown how the OXTR gene may be linked to the functional anatomy of
other relevant brain regions that include the fusiform gyrus (FG), superior
temporal sulcus (STS), ventromedial prefrontal cortex (VMPFC), temporoparietal
junction (TPJ) and nucleus accumbens (NAcc). We conclude by highlighting
potential future research directions that may elucidate the path between OXTR and
complex behaviors such as cooperation.
PMID- 24348361
TI - Reading into neuronal oscillations in the visual system: implications for
developmental dyslexia.
AB - While phonological impairments are common in developmental dyslexia, there has
recently been much debate as to whether there is a causal link between the
phonological difficulties and the reading problem. An alternative suggestion has
been gaining ground that the core deficit in dyslexia is in visual attentional
mechanisms. If so, the visual aetiology may be at any of a number of sites along
the afferent magnocellular pathway or in the dorsal cortical stream that are all
essential for a visuo-spatial attentional feedback to the primary visual cortex.
It has been suggested that the same circuits and pathways of top-down attention
used for serial visual search are used for reading. Top-down signals from the
dorsal parietal areas to primary visual cortex serially highlight cortical
locations representing successive letters in a text before they can be recognized
and concatenated into a word. We had shown in non-human primates that the
mechanism of such a top-down feedback in a visual attention task uses
synchronized neuronal oscillations at the lower end of the gamma frequency range.
It is no coincidence that reading graphemes in a text also happens at the low
gamma frequencies. The basic proposal here is that each cycle of gamma
oscillation focuses an attentional spotlight on the primary visual cortical
representation of just one or two letters before sequential recognition of
letters and their concatenation into word strings. The timing, period, envelope,
amplitude, and phase of the synchronized oscillations modulating the incoming
signals in the striate cortex would have a profound influence on the accuracy and
speed of reading. Thus, the general temporal sampling difficulties in dyslexic
subjects may impact reading not necessarily by causing phonological deficits, but
by affecting the spatio-temporal parsing of the visual input within the visual
system before these signals are used for letter and word recognition.
PMID- 24348362
TI - A new methodical approach in neuroscience: assessing inter-personal brain
coupling using functional near-infrared imaging (fNIRI) hyperscanning.
AB - Since the first demonstration of how to simultaneously measure brain activity
using functional magnetic resonance imaging (fMRI) on two subjects about 10 years
ago, a new paradigm in neuroscience is emerging: measuring brain activity from
two or more people simultaneously, termed "hyperscanning". The hyperscanning
approach has the potential to reveal inter-personal brain mechanisms underlying
interaction-mediated brain-to-brain coupling. These mechanisms are engaged during
real social interactions, and cannot be captured using single-subject recordings.
In particular, functional near-infrared imaging (fNIRI) hyperscanning is a
promising new method, offering a cost-effective, easy to apply and reliable
technology to measure inter-personal interactions in a natural context. In this
short review we report on fNIRI hyperscanning studies published so far and
summarize opportunities and challenges for future studies.
PMID- 24348363
TI - Age related changes in striatal resting state functional connectivity in autism.
AB - Characterizing the nature of developmental change is critical to understanding
the mechanisms that are impaired in complex neurodevelopment disorders such as
autism spectrum disorder (ASD) and, pragmatically, may allow us to pinpoint
periods of plasticity when interventions are particularly useful. Although
aberrant brain development has long been theorized as a characteristic feature of
ASD, the neural substrates have been difficult to characterize, in part due to a
lack of developmental data and to performance confounds. To address these issues,
we examined the development of intrinsic functional connectivity, with resting
state fMRI from late childhood to early adulthood (8-36 years), using a seed
based functional connectivity method with the striatal regions. Overall, we found
that both groups show decreases in cortico-striatal circuits over age. However,
when controlling for age, ASD participants showed increased connectivity with
parietal cortex and decreased connectivity with prefrontal cortex relative to
typically developed (TD) participants. In addition, ASD participants showed
aberrant age-related connectivity with anterior aspects of cerebellum, and
posterior temporal regions (e.g., fusiform gyrus, inferior and superior temporal
gyri). In sum, we found prominent differences in the development of striatal
connectivity in ASD, most notably, atypical development of connectivity in
striatal networks that may underlie cognitive and social reward processing. Our
findings highlight the need to identify the biological mechanisms of
perturbations in brain reorganization over development, which may also help
clarify discrepant findings in the literature.
PMID- 24348364
TI - Brain mechanisms underlying the impact of attachment-related stress on social
cognition.
AB - Mentalizing, in particular the successful attribution of complex mental states to
others, is crucial for navigating social interactions. This ability is highly
influenced by external factors within one's daily life, such as stress. We
investigated the impact of stress on the brain basis of mentalization in adults.
Using a novel modification of the Reading the Mind in the Eyes Test (RMET-R) we
compared the differential effects of two personalized stress induction
procedures: a general stress induction (GSI) and an attachment-related stress
induction (ASI). Participants performed the RMET-R at baseline and after each of
the two inductions. Baseline results replicated and extended previous findings
regarding the neural correlates of the RMET-R. Additionally, we identified brain
regions associated with making complex age judgments from the same stimuli.
Results after stress exposure showed that the ASI condition resulted in reduced
mentalization-related activation in the left posterior superior temporal sulcus
(STS), left inferior frontal gyrus and left temporoparietal junction (TPJ).
Moreover, the left middle frontal gyrus and left anterior insula showed greater
functional connectivity to the left posterior STS after the ASI. Our findings
indicate that attachment-related stress has a unique effect on the neural
correlates of mentalization.
PMID- 24348365
TI - Using action observation to study superior motor performance: a pilot fMRI study.
AB - The most efficient way to acquire motor skills may be through physical practice.
Nevertheless, it has also been shown that action observation may improve motor
performance. The aim of the present pilot study was to examine a potential action
observation paradigm used to (1) capture the superior performance of expert
athletes and (2) capture the underlying neural mechanisms of successful action
observation in relation to task experience. We used functional magnetic resonance
imaging to measure regional blood flow while presenting videos of a hockey player
shooting a puck toward a hockey goal. The videos (a total of 120) where stopped
at different time frames with different amount of information provided, creating
a paradigm with three different levels of difficulty to decide the fate of a
shot. Since this was only a pilot study, we first tested the paradigm
behaviorally on six elite expert hockey players, five intermediate players, and
six non-hockey playing controls. The results showed that expert hockey players
were significantly (p < 0.05) more accurate on deciding the fate of the action
compared to the others. Thus, it appears as if the paradigm can capture superior
performance of expert athletes (aim 1). We then tested three of the hockey
players and three of the controls on the same paradigm in the MRI scanner to
investigate the underlying neural mechanisms of successful action anticipation.
The imaging results showed that when expert hockey players observed and correctly
anticipated situations, they recruited motor and temporal regions of the brain.
Novices, on the other hand, relied on visual regions during observation and
prefrontal regions during action decision. Thus, the results from the imaging
data suggest that different networks of the brain are recruited depending on task
experience (aim 2). In conclusion, depending on the level of motor skill of the
observer, when correctly anticipating actions different neural systems will be
recruited.
PMID- 24348366
TI - Neural networks underlying affective states in a multimodal virtual environment:
contributions to boredom.
AB - The interaction of low perceptual stimulation or goal-directed behavior with a
negative subjective evaluation may lead to boredom. This contribution to boredom
may shed light on its neural correlates, which are poorly characterized so far. A
video game served as simulation of free interactive behavior without interruption
of the game's narrative. Thirteen male German volunteers played a first-person
shooter game (Tactical Ops: Assault on Terror) during functional magnetic
resonance imaging (fMRI). Two independent coders performed the time-based
analysis of the audio-visual game content. Boredom was operationalized as
interaction of prolonged absence of goal-directed behavior with lowered affect in
the Positive and Negative Affect Schedule (PANAS). A decrease of positive affect
(PA) correlated with response amplitudes in bilateral insular clusters extending
into the amygdala to prolonged inactive phases in a game play and an increase in
negative affect (NA) was associated with higher responses in bilateral
ventromedial prefrontal cortex (vmPFC). Precuneus and hippocampus responses were
negatively correlated with changes in NA. We describe for the first time neural
contributions to boredom, using a video game as complex virtual environment.
Further our study confirmed that PA and NA are separable constructs, reflected by
distinct neural patterns. PA may be associated with afferent limbic activity
whereas NA with affective control.
PMID- 24348367
TI - Resolving the orthographic ambiguity during visual word recognition in Arabic: an
event-related potential investigation.
AB - The Arabic alphabetical orthographic system has various unique features that
include the existence of emphatic phonemic letters. These represent several pairs
of letters that share a phonological similarity and use the same parts of the
articulation system. The phonological and articulatory similarities between these
letters lead to spelling errors where the subject tends to produce a
pseudohomophone (PHw) instead of the correct word. Here, we investigated whether
or not the unique orthographic features of the written Arabic words modulate
early orthographic processes. For this purpose, we analyzed event-related
potentials (ERPs) collected from adult skilled readers during an orthographic
decision task on real words and their corresponding PHw. The subjects' reaction
times (RTs) were faster in words than in PHw. ERPs analysis revealed significant
response differences between words and the PHw starting during the N170 and
extending to the P2 component, with no difference during processing steps devoted
to phonological and lexico-semantic processing. Amplitude and latency differences
were found also during the P6 component which peaked earlier for words and where
source localization indicated the involvement of the classical left language
areas. Our findings replicate some of the previous findings on PHw processing and
extend them to involve early orthographical processes.
PMID- 24348368
TI - How culture influences perspective taking: differences in correction, not
integration.
AB - Individuals from East Asian (Chinese) backgrounds have been shown to exhibit
greater sensitivity to a speaker's perspective than Western (U.S.) participants
when resolving referentially ambiguous expressions. We show that this cultural
difference does not reflect better integration of social information during
language processing, but rather is the result of differential correction: in the
earliest moments of referential processing, Chinese participants showed
equivalent egocentric interference to Westerners, but managed to suppress the
interference earlier and more effectively. A time-series analysis of visual-world
eye-tracking data found that the two cultural groups diverged extremely late in
processing, between 600 and 1400 ms after the onset of egocentric interference.
We suggest that the early moments of referential processing reflect the operation
of a universal stratum of processing that provides rapid ambiguity resolution at
the cost of accuracy and flexibility. Late components, in contrast, reflect the
mapping of outputs from referential processes to decision-making and action
planning systems, allowing for a flexibility in responding that is molded by
culturally specific demands.
PMID- 24348370
TI - The impact of physical exercise on convergent and divergent thinking.
AB - Anecdotal literature suggests that creative people sometimes use bodily movement
to help overcome mental blocks and lack of inspiration. Several studies have
shown that physical exercise may sometimes enhance creative thinking, but the
evidence is still inconclusive. In this study we investigated whether creativity
in convergent- and divergent-thinking tasks is affected by acute moderate and
intense physical exercise in athletes (n = 48) and non-athletes (n = 48).
Exercise interfered with divergent thinking in both groups. The impact on
convergent thinking, the task that presumably required more cognitive control,
depended on the training level: while in non-athletes performance was
significantly impaired by exercise, athletes showed a benefit that approached
significance. The findings suggest that acute exercise may affect both, divergent
and convergent thinking. In particular, it seems to affect control-hungry tasks
through exercise-induced "ego-depletion," which however is less pronounced in
individuals with higher levels of physical fitness, presumably because of the
automatization of movement control, fitness-related neuroenergetic benefits, or
both.
PMID- 24348371
TI - Expertise and processing distorted structure in chess.
AB - A classic finding in research on human expertise and knowledge is that of
enhanced memory for stimuli in a domain of expertise as compared to either
stimuli outside that domain, or within-domain stimuli that have been degraded or
distorted in some way. However, we do not understand how experts process
degradation or distortion of stimuli within the expert domain (e.g., a face with
the eyes, nose, and mouth in the wrong positions, or a chessboard with pieces
placed randomly). Focusing on the domain of chess, we present new fMRI evidence
that when experts view such distorted/within-domain stimuli, they engage an
active search for structure-a kind of exploratory chunking-that involves a
component of a prefrontal-parietal network linked to consciousness, attention and
working memory.
PMID- 24348372
TI - Patterns of interval correlations in neural oscillators with adaptation.
AB - Neural firing is often subject to negative feedback by adaptation currents. These
currents can induce strong correlations among the time intervals between spikes.
Here we study analytically the interval correlations of a broad class of noisy
neural oscillators with spike-triggered adaptation of arbitrary strength and time
scale. Our weak-noise theory provides a general relation between the correlations
and the phase-response curve (PRC) of the oscillator, proves anti-correlations
between neighboring intervals for adapting neurons with type I PRC and identifies
a single order parameter that determines the qualitative pattern of correlations.
Monotonically decaying or oscillating correlation structures can be related to
qualitatively different voltage traces after spiking, which can be explained by
the phase plane geometry. At high firing rates, the long-term variability of the
spike train associated with the cumulative interval correlations becomes small,
independent of model details. Our results are verified by comparison with
stochastic simulations of the exponential, leaky, and generalized integrate-and
fire models with adaptation.
PMID- 24348373
TI - Computational model of precision grip in Parkinson's disease: a utility based
approach.
AB - We propose a computational model of Precision Grip (PG) performance in normal
subjects and Parkinson's Disease (PD) patients. Prior studies on grip force
generation in PD patients show an increase in grip force during ON medication and
an increase in the variability of the grip force during OFF medication
(Ingvarsson et al., 1997; Fellows et al., 1998). Changes in grip force generation
in dopamine-deficient PD conditions strongly suggest contribution of the Basal
Ganglia, a deep brain system having a crucial role in translating dopamine
signals to decision making. The present approach is to treat the problem of
modeling grip force generation as a problem of action selection, which is one of
the key functions of the Basal Ganglia. The model consists of two components: (1)
the sensory-motor loop component, and (2) the Basal Ganglia component. The
sensory-motor loop component converts a reference position and a reference grip
force, into lift force and grip force profiles, respectively. These two forces
cooperate in grip-lifting a load. The sensory-motor loop component also includes
a plant model that represents the interaction between two fingers involved in PG,
and the object to be lifted. The Basal Ganglia component is modeled using
Reinforcement Learning with the significant difference that the action selection
is performed using utility distribution instead of using purely Value-based
distribution, thereby incorporating risk-based decision making. The proposed
model is able to account for the PG results from normal and PD patients
accurately (Ingvarsson et al., 1997; Fellows et al., 1998). To our knowledge the
model is the first model of PG in PD conditions.
PMID- 24348374
TI - The emergence of two anti-phase oscillatory neural populations in a computational
model of the Parkinsonian globus pallidus.
AB - Experiments in rodent models of Parkinson's disease have demonstrated a prominent
increase of oscillatory firing patterns in neurons within the Parkinsonian globus
pallidus (GP) which may underlie some of the motor symptoms of the disease. There
are two main pathways from the cortex to GP: via the striatum and via the
subthalamic nucleus (STN), but it is not known how these inputs sculpt the
pathological pallidal firing patterns. To study this we developed a novel neural
network model of conductance-based spiking pallidal neurons with cortex-modulated
input from STN neurons. Our results support the hypothesis that entrainment
occurs primarily via the subthalamic pathway. We find that as a result of the
interplay between excitatory input from the STN and mutual inhibitory coupling
between GP neurons, a homogeneous population of GP neurons demonstrates a self
organizing dynamical behavior where two groups of neurons emerge: one spiking in
phase with the cortical rhythm and the other in anti-phase. This finding mirrors
what is seen in recordings from the GP of rodents that have had Parkinsonism
induced via brain lesions. Our model also includes downregulation of
Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels in response to
burst firing of GP neurons, since this has been suggested as a possible mechanism
for the emergence of Parkinsonian activity. We found that the downregulation of
HCN channels provides even better correspondence with experimental data but that
it is not essential in order for the two groups of oscillatory neurons to appear.
We discuss how the influence of inhibitory striatal input will strengthen our
results.
PMID- 24348369
TI - Modulation of human corticospinal excitability by paired associative stimulation.
AB - Paired Associative Stimulation (PAS) has come to prominence as a potential
therapeutic intervention for the treatment of brain injury/disease, and as an
experimental method with which to investigate Hebbian principles of neural
plasticity in humans. Prototypically, a single electrical stimulus is directed to
a peripheral nerve in advance of transcranial magnetic stimulation (TMS)
delivered to the contralateral primary motor cortex (M1). Repeated pairing of the
stimuli (i.e., association) over an extended period may increase or decrease the
excitability of corticospinal projections from M1, in manner that depends on the
interstimulus interval (ISI). It has been suggested that these effects represent
a form of associative long-term potentiation (LTP) and depression (LTD) that
bears resemblance to spike-timing dependent plasticity (STDP) as it has been
elaborated in animal models. With a large body of empirical evidence having
emerged since the cardinal features of PAS were first described, and in light of
the variations from the original protocols that have been implemented, it is
opportune to consider whether the phenomenology of PAS remains consistent with
the characteristic features that were initially disclosed. This assessment
necessarily has bearing upon interpretation of the effects of PAS in relation to
the specific cellular pathways that are putatively engaged, including those that
adhere to the rules of STDP. The balance of evidence suggests that the mechanisms
that contribute to the LTP- and LTD-type responses to PAS differ depending on the
precise nature of the induction protocol that is used. In addition to emphasizing
the requirement for additional explanatory models, in the present analysis we
highlight the key features of the PAS phenomenology that require interpretation.
PMID- 24348376
TI - Learning in brain and machine-complexity, Godel, Aristotle.
PMID- 24348375
TI - EEG theta and Mu oscillations during perception of human and robot actions.
AB - The perception of others' actions supports important skills such as
communication, intention understanding, and empathy. Are mechanisms of action
processing in the human brain specifically tuned to process biological agents?
Humanoid robots can perform recognizable actions, but can look and move
differently from humans, and as such, can be used in experiments to address such
questions. Here, we recorded EEG as participants viewed actions performed by
three agents. In the Human condition, the agent had biological appearance and
motion. The other two conditions featured a state-of-the-art robot in two
different appearances: Android, which had biological appearance but mechanical
motion, and Robot, which had mechanical appearance and motion. We explored
whether sensorimotor mu (8-13 Hz) and frontal theta (4-8 Hz) activity exhibited
selectivity for biological entities, in particular for whether the visual
appearance and/or the motion of the observed agent was biological. Sensorimotor
mu suppression has been linked to the motor simulation aspect of action
processing (and the human mirror neuron system, MNS), and frontal theta to
semantic and memory-related aspects. For all three agents, action observation
induced significant attenuation in the power of mu oscillations, with no
difference between agents. Thus, mu suppression, considered an index of MNS
activity, does not appear to be selective for biological agents. Observation of
the Robot resulted in greater frontal theta activity compared to the Android and
the Human, whereas the latter two did not differ from each other. Frontal theta
thus appears to be sensitive to visual appearance, suggesting agents that are not
sufficiently biological in appearance may result in greater memory processing
demands for the observer. Studies combining robotics and neuroscience such as
this one can allow us to explore neural basis of action processing on the one
hand, and inform the design of social robots on the other.
PMID- 24348378
TI - Verrucous spitz nevus in a Japanese female.
AB - A 23-year-old female presented with a reddish-brown dome-shaped hyperkeratotic
nodule of 11 * 10 mm on the left lower leg. Dermoscopic examination demonstrated
a prominent whitish scaly area with ring-like appearance, pinkish-white
structureless areas, a few milia-like cysts, dotted and glomerular vessels, and
light brown globules. The lesion was completely excised under the diagnosis of
verruca vulgaris or dermatofibroma. Histopathological examination revealed a well
circumscribed symmetric lesion with hyperkeratosis, acanthosis, and pseudohorn
cysts. The lesion was composed of spindle-shaped and epithelioid melanocytes with
large cytoplasm arranged in confluent nests surrounded by stromal fibrosis.
Mitotic figures and Kamino bodies were absent. Moderate proliferation of
capillaries was found in the papillary dermis. Immunohistochemical staining with
melan-A or S-100 was positive for tumor cells, but the staining with HMB-45 was
negative. Melan-A staining was weaker in the deeply situated cells than in the
superficial ones, which is known as stratification. Finally, we made a diagnosis
of verrucous Spitz nevus based on these findings. We should have been aware of
the entity of verrucous Spitz nevus as a variant of Spitz nevus and its
dermoscopic features in order to reach a correct diagnosis before excision.
PMID- 24348377
TI - Self-assembled liposomal nanoparticles in photodynamic therapy.
AB - Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers
(PS) together with harmless visible light of the appropriate wavelength to
produce reactive oxygen species that kill unwanted cells. Because many PS are
hydrophobic molecules prone to aggregation, numerous drug delivery vehicles have
been tested to solubilize these molecules, render them biocompatible and enhance
the ease of administration after intravenous injection. The recent rise in
nanotechnology has markedly expanded the range of these nanoparticulate delivery
vehicles beyond the well-established liposomes and micelles. Self-assembled
nanoparticles are formed by judicious choice of monomer building blocks that
spontaneously form a well-oriented 3-dimensional structure that incorporates the
PS when subjected to the appropriate conditions. This self-assembly process is
governed by a subtle interplay of forces on the molecular level. This review will
cover the state of the art in the preparation and use of self-assembled liposomal
nanoparticles within the context of PDT.
PMID- 24348379
TI - Scleromyxedema with subcutaneous nodules: successful treatment with thalidomide
and intravenous immunoglobulin.
AB - Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized
papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic
manifestations. An atypical clinical presentation with cutaneous and subcutaneous
nodules has been reported rarely. In recent years, intravenous immunoglobulin
(IVIg) appears to be the therapy of choice for scleromyxedema. Treatment
experiences in atypical manifestations with mucinous nodules are limited to
sporadic reports. We report the case of male patient with atypical scleromyxedema
without underlying paraproteinemia, presenting with generalized papular and
sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers
and face as well as on the eyelids, and associated systemic symptoms. Complete
regression of all cutaneous lesions and extracutaneous symptoms with sustained
remission was achieved by combined treatment with thalidomide and IVIg.
PMID- 24348380
TI - A case report of atypical scrotal leiomyoma.
AB - Scrotal leiomyoma is a benign tumor derived from the scrotal dartos muscle; it is
rare in clinical findings. The cause of the disease is not yet clear. Here, we
present the case of a patient with no typical clinical features, but with some
typical pathological changes. A middle-aged male patient saw a doctor for
paroxysmal itching and burning of the scrotum. The physical examination revealed
3 * 5-cm(2), ill-defined, pink plaques, an uneven surface, and basal infiltration
with pigmentation defects in the center. Pathology results showed dermal spindle
cells in nodular hyperplasia. The nucleus was round at both ends, a perinuclear
halo could be seen, and staining was positive for actin and negative for S100.
Therefore, the diagnosis of scrotal myoma was made.
PMID- 24348381
TI - Genital vulvar lichen sclerosus in monozygotic twin women: a case report and
review of the literature.
AB - Lichen sclerosus et atrophicus is a skin disease of multifactorial etiology which
appears in patients with genetic or hormonal predisposition and autoimmune
disease. Genetic predisposition is suggested by familial reports of the disease
which involve twins, siblings, and mother-daughter/son series. This is a report
of the occurrence of lichen sclerosus et atrophicus in monozygotic twin women,
suggesting that inheritance is of relevance in the etiology of this disease.
PMID- 24348382
TI - Paradoxical Reaction to Golimumab: Tumor Necrosis Factor alpha Inhibitor Inducing
Psoriasis Pustulosa.
AB - IMPORTANCE: Golimumab is a human monoclonal antibody, used for rheumatoid
arthritis, psoriatic arthritis and ankylosing spondylitis. Adverse reactions are
increasing with this class of medication (tumor necrosis factor alpha
inhibitors). OBSERVATIONS: The authors present a case of a female patient who
presented with psoriasis pustulosa after the use of golimumab for rheumatoid
arthritis. CONCLUSIONS AND RELEVANCE: Paradoxically, in this case, golimumab,
which is used for psoriasis, induced the pustular form of this disease. We are
observing an increasing number of patients who develop collateral effects with
tumor necrosis factor alpha inhibitors, and the understanding of the mechanism of
action and how these adverse reactions occur may contribute to avoid these
sometimes severe situations.
PMID- 24348383
TI - Adalimumab in recalcitrant severe psoriasis associated with atopic dermatitis.
AB - Tumor necrosis factor-alpha inhibitors may induce various cutaneous side effects
including eczematous-like lesions. The management of such side effects can be
challenging. Herein, we report a case of a 55-year-old man who had a flare-up and
subsequent improvement of atopic dermatitis during treatment of severe psoriasis
with adalimumab.
PMID- 24348384
TI - Allergic contact dermatitis induced by textile necklace.
AB - Allergic contact dermatitis to textile dyes is considered to be a rare
phenomenon. A recent review reported a prevalence of contact allergy to disperse
dyes between 0.4 and 6.7%. The relevance of positive patch testing was not
reported in all studies. Textile dye allergy is easily overlooked and is
furthermore challenging to investigate as textile dyes are not labelled on
clothing. In this report, we present a case of allergic contact dermatitis to a
textile necklace. The patch test showed strong reactions to the necklace and the
azo dyes Disperse Orange 1 and Disperse Yellow 3. Despite the European
legislation and the reduced use of disperse dyes in Third World countries,
disperse azo dyes still induce new cases of allergic contact dermatitis.
PMID- 24348385
TI - Effects of a facial cream containing the minor alkaloid anatabine on improving
the appearance of the skin in mild to moderate rosacea: an open-label case series
study.
AB - BACKGROUND: Current medical and scientific research indicates that rosacea, a
chronic and often debilitating skin condition that primarily affects the central
face, may be caused by an overactive or excessive inflammatory immune response.
Regardless of etiology, the accompanying redness and inflammation is unsightly
and difficult for the patient. Anatabine is an alkaloid from the plant family
Solanaceae that has been shown in several preclinical studies to modulate
proinflammatory signaling pathways. OBJECTIVE: A cream containing anatabine was
developed and evaluated in an open-label case series study for safety and effects
on the appearance of the skin in 10 patients with mild to moderate rosacea.
METHODS: Patients applied the cream to the face twice daily for a period of 30
days. Patients and the study physician completed safety and efficacy assessments
at study end. RESULTS: Results showed that 50% of the patients self-reported
improvement in the appearance of their skin, and the physician noted improvement
in 70% of the patients. Photographs taken before and after 30 days of cream use
provide visual evidence of the improvement in several patients. There were no
complications or adverse events reported by any of the patients in the study,
indicating that the anatabine cream was safe and very well tolerated. CONCLUSION:
The results of this open-label case series show that a facial cream containing
anatabine can improve the appearance of the skin in patients with mild to
moderate rosacea and suggest that a double-blind, vehicle-controlled trial in a
larger number of subjects is warranted.
PMID- 24348386
TI - Hyperpigmentation following Treatment of Frontal Fibrosing Alopecia.
AB - INTRODUCTION: Frontal fibrosing alopecia (FFA) is a scarring alopecia
characterized by progressive recession of the frontotemporal hairline. Current
treatment is aimed at stopping progression, and the combination of dutasteride
and pimecrolimus is the most effective therapy. Side effects associated with
dutasteride are erectile dysfunction as well as breast tenderness and
enlargement, while pimecrolimus produces a burning sensation. CASE REPORT: We
present a 57-year-old postmenopausal female with a 3-year history of a scarring
alopecic plaque in her frontotemporal region. Biopsy confirmed the diagnosis of
FFA, and she was started on dutasteride 0.5 mg p.o. q.d., and later, topical
pimecrolimus 1% b.i.d. was added. Eight months after initiating treatment, she
showed hyperpigmentation on her metacarpophalangeal and interphalangeal joints,
as well as on the cheeks and on the chin; dutasteride and pimecrolimus were
discontinued. After 5 months of follow-up, her hyperpigmentation improved by 80%
only by using photoprotection. CONCLUSION: Because of the variable clinical
course of FFA, treatment is focused on halting its progression. Several
therapeutic agents have been evaluated and the combination of dutasteride and
pimecrolimus has shown a high response rate. There is no reported evidence of
hyperpigmentation associated with this combination.
PMID- 24348387
TI - Incidental discovery of testicular microlithiasis: what is the importance of
ultrasound surveillance? Two case reports.
AB - Many studies have demonstrated an association between diffuse bilateral
testicular microlithiasis (TM) and gonadal and extragonadal germ cell tumors.
Nevertheless, it is still uncertain whether ultrasound surveillance is really
necessary in patients with TM in the absence of other risk factors such as
previous testicular cancer, a history of cryptorchidism or testicular atrophy. We
report the cases of a 33- and a 39-year-old man presenting with a retroperitoneal
extragonadal tumor. The first patient underwent an MRI examination in order to
rule out a lumbosacral hernia: MRI images showed no slipped disks but a
voluminous retroperitoneal solid mass. The histological analysis revealed an
immature teratoma. The second patient came to the emergency department
complaining of abdominal pain, vomiting, weight loss and mild jaundice:
ultrasound examination showed a large, ill-defined heterogeneous abdominal mass,
confirmed by CT and MRI examination. The histology diagnosed a yolk sac tumor. In
both patients, the testicular sonography was performed to rule out a focal
lesion, but it displayed bilateral TM without a focal testicular mass. Based on
our direct experience, we highlight the importance of annual ultrasonographic
surveillance of the testis and the retroperitoneal space in patients with
occasionally detected TM.
PMID- 24348388
TI - Successful chemotherapy with Carboplatin and s-1 for thymic carcinoma: a case
report.
AB - Thymic carcinoma is a rare but aggressive neoplasm. Although there is no clearly
optimal first- or second-line chemotherapy regimen for thymic carcinoma, platinum
based chemotherapy has repeatedly been shown to be of benefit to patients with
advanced thymic carcinoma. Some case reports have described S-1 as a novel agent
with good activity against advanced thymic carcinoma. A 74-year-old female was
diagnosed with thymic carcinoma complicated by pleural dissemination and
pericardial effusion of carcinomatosa. She was treated with carboplatin on day 1
plus S-1 on days 1-14 in cycles repeated every 3 or 4 weeks. Four cycles of this
regimen were administered, and a partial response was confirmed. There were no
severe hematological or nonhematological toxicities, and no dose reduction was
necessary. To our knowledge, this is the first report to demonstrate the efficacy
of combination chemotherapy consisting of carboplatin and S-1 against thymic
carcinoma.
PMID- 24348389
TI - Early relapse of unresectable gallbladder cancer after discontinuation of
gemcitabine monotherapy administered for 5 years in a patient who had complete
response to the treatment.
AB - The tumor shrinkage effect of gemcitabine is considered to be limited in cases of
advanced gallbladder cancer, and there are few reports of complete response to
gemcitabine therapy in patients with this cancer. Therefore, the treatment
continuation strategy in these patients, after a complete response has been
achieved, still remains to be established. Here, we present the case of a 77-year
old patient with unresectable gallbladder cancer, who after showing complete
response to gemcitabine monotherapy administered for 5 years, showed early
relapse within only 11 months of discontinuation of the drug. Thus, it is
necessary to establish a suitable treatment continuation strategy for patients
who show complete response to gemcitabine treatment.
PMID- 24348390
TI - A husband and a wife with simultaneous presentation of glioblastoma multiforme: a
case report.
AB - Glioblastoma multiforme (GBM) is the most lethal subtype of glioma, classified as
a WHO grade 4 infiltrative glioma. The etiology of GBM remains unknown and risk
factors can be identified only in a small minority. We report the synchronous
occurrence of GBM in an otherwise unrelated married couple, i.e. a husband and
his wife, who developed GBM within an interval of 1 month. No specific causative
environmental factors were identified for both patients, and the genetic screens
were negative for hereditary syndromes. Family history was negative for tumors,
and no other incidence of cancer in either siblings, parents or other children
was reported. An analysis of the couple's exposure to nonionizing electromagnetic
fields and ionizing radiations revealed values within the normal ranges usually
found in homes. Overall, conjugal tumors are rarely reported. However, the case
reported herein raises important questions about possible etiologic factors.
PMID- 24348391
TI - Growing teratoma syndrome of the ovary showing three patterns of metastasis: a
case report.
AB - Growing teratoma syndrome (GTS) is defined as metastatic masses during or after
chemotherapy for germ cell tumors, which contain only mature teratoma components.
The peritoneum of the pelvis and abdomen and the retroperitoneum are the most
frequent sites of metastasis. We report a case of GTS of the ovary showing three
patterns of metastasis: dissemination, lymphogenous metastasis, and hematogenous
metastasis. The patient initially presented 5 years ago with a mixed germ cell
tumor of the left ovary and positive cytology of ascites. After surgery and
chemotherapy, mature teratomas recurred as pelvic peritoneal dissemination, a
para-aortic lymph node mass, and a lung mass. Our case highlights the importance
of long-term follow-up and a whole-body search. We think that our case is
suggestive regarding the mechanism of critical GTS.
PMID- 24348392
TI - Use of an Amplatzer Device for Endoscopic Closure of a Large Bronchopleural
Fistula following Lobectomy for a Stage I Squamous Cell Carcinoma.
AB - Bronchopleural fistulas can occur as a rare but severe complication after
pulmonary resection. Established guidelines for the proper treatment of patients
with bronchopleural fistulas do not exist. Apart from attempts to close the
fistula, emphasis is placed on preventive measures, early treatment with
antibiotics, drainage of the empyema and aggressive nutritional and
rehabilitative support. For inoperable patients, endoscopic procedures are the
only therapeutic option. Unfortunately, large (>8 mm) or central bronchopleural
fistulas are usually not suitable for such endoscopic management. Recently, some
groups have published a few case reports about a novel technique for the
endobronchial closure of bronchopleural fistulas, using an Amplatzer device,
originally designed for transcatheter closure of cardiac septal defects. We
applied the same technique as a life-saving treatment in a ventilated patient who
was considered inoperable due to a high oxygen need. The operation was
successful. The patient could be weaned from ventilation and was eventually
discharged from the hospital to a rehabilitation facility several weeks after the
insertion of the device. Until now, endoscopic techniques have only been useful
for the treatment of small, peripheral, bronchopleural fistulas and even then
only as a bridge to surgery in high-risk surgical patients. In this case report,
we demonstrate that the use of an Amplatzer device can expand the importance of
endoscopic techniques in the treatment of bronchopleural fistulas. An Amplatzer
device, for endobronchial closure, can indeed be administered for large and
central bronchopleural fistulas. Moreover, it can be considered as a definite
alternative to surgery in inoperable patients.
PMID- 24348393
TI - Gastric and endobronchial metastases in a case of lobular breast cancer.
AB - BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common
histological type of invasive breast carcinoma, preceded only by infiltrating
ductal carcinoma, which has clinical, biological and molecular distinctions.
These distinctions imply a different metastatic behavior between the histology of
these 2 types of breast cancer. CASE PRESENTATION: We report the case of a 51
year-old woman with breast cancer with ILC histology, diagnosed at an early
stage. In the course of her disease, recurrences in the gastric mucosa and
endobronchial area occurred. The treatment she received is described herein.
CONCLUSION: This is a case of ILC with unusual metastases. The absence of E
cadherin is related to the carcinogenesis of ILC and probably to these patterns
of metastasis as well.
PMID- 24348394
TI - Presacral ganglioneuroma: diagnostic considerations and therapeutic strategy.
AB - Presacral ganglioneuroma is an extremely rare tumor of neural crest origin. To
the best of our knowledge, less than 20 cases have been reported previously. The
present study reports on a presacral ganglioneuroma, 10.5 * 8 * 4 cm in size,
that was found incidentally in a 35-year-old man with prior history of
diverticulitis. He was admitted to our hospital due to lower left abdominal pain.
Abdominal computed tomography and magnetic resonance imaging confirmed the
extension of the lesion from the S2 level to the coccyx. The mass had low signal
intensity on T1-weighted images and heterogeneous high signal intensity on T2
weighted images with no intraspinal or rectal extension. T2-weighted images
demonstrated a compartmentalized solid tumor with cystic components. Complete
tumor resection with free surgical margins was achieved using an abdominal
approach. The patient remains asymptomatic 2 years after surgery. We emphasize on
clinical features, radiologic appearance and surgical treatment of this rare
entity. The clinical and pathologic features of previously reported studies are
also briefly reviewed.
PMID- 24348395
TI - Long survival of a small-cell lung cancer patient who received maintenance
chemotherapy with irinotecan.
AB - Lung cancer is the leading cause of cancer-related death worldwide. Small-cell
lung cancer (SCLC) accounts for approximately 15% of all lung cancers. It is
characterized by rapid tumor growth and early metastasis to multiple organs.
Response to initial chemotherapy is generally good; however, the majority of
patients develop recurrence and the prognosis of such patients is reportedly 2-4
months. Evolution of the treatment for SCLC has stagnated, and cisplatin +
etoposide has been the standard chemotherapy for decades. Meanwhile, the
combination of cisplatin + irinotecan has demonstrated equivalent efficacy to
cisplatin + etoposide. Recently, maintenance chemotherapy has been extensively
investigated in non-small-cell lung cancer (NSCLC), and is currently recommended
as a standard treatment in clinical guidelines. On the contrary, a maintenance
strategy has not been established for SCLC. Here, we describe an SCLC patient who
received maintenance chemotherapy with irinotecan for more than 2 years after
induction chemotherapy with cisplatin + irinotecan, and survived long term with
no recurrence.
PMID- 24348396
TI - A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine
Therapy Alone.
AB - This report presents a case that shows a significant anticancer effect of Korean
medicine therapy (KMT). A 79-year-old man, who was diagnosed as stage IV non
small cell lung cancer (NSCLC) in December 2012, was treated with KMT including
intravenous pharmacopunctures and oral herbal medicine from February 22, 2013,
until September 2013 without any surgical intervention, chemotherapy or
radiotherapy. The intravenous pharmacopunctures were the wild ginseng
pharmacopuncture, Cordyceps sinensis pharmacopuncture and Trichosanthes kirilowii
pharmacopuncture. The oral herbal medicine used was soramdan, made of cultivated
wild ginseng. The effectiveness of this therapy was evaluated with computed
tomography and the Eastern Cooperative Oncology Group (ECOG) performance scale.
The size of the tumor mass was markedly decreased and the ECOG performance scale
was also improved. These results suggest that KMT alone can be an effective
method to treat NSCLC.
PMID- 24348397
TI - Esophageal gastrointestinal stromal tumors presenting as mediastinal mass.
AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
the gastrointestinal tract and are predominant in the stomach and intestine but
rare in the esophagus. Here, we report a case of esophageal GIST which presented
as a mediastinal mass on chest X-ray and dyspnea. The case was initially
diagnosed as leiomyosarcoma, which could create a diagnostic dilemma. Therefore,
recognizing this uncommon presentation as a mediastinal mass with esophageal GIST
is important in the differential diagnosis.
PMID- 24348398
TI - Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion
Body Myopathy due to the VCP Mutation (R155H) in a French Family.
AB - INTRODUCTION: Inclusion body myopathy with Paget's disease of the bone and
frontotemporal dementia (IBMPFD) is a rare late-onset autosomal dominant disorder
due to a mutation of the valosin-containing protein (VCP) gene. CASE REPORT: We
report the case of a patient who developed progressive weakness of the limbs in
his fifties, until he was confined to a wheelchair. At that time, he developed
acute behavioural changes including irritability, severe anxiety and major
depression, which led to him being hospitalised in a psychiatric hospital. He
also suffered from aphasia and executive function impairment, which helped us to
diagnose a behavioural form of frontotemporal dementia (FTD). The diagnosis of
IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the
VCP gene (R155H mutation). DISCUSSION: THE CLINICAL DIAGNOSIS OF IBMPFD IS
SUGGESTED BY THE PRESENCE OF AT LEAST ONE OF THREE MAJOR MANIFESTATIONS AS
FOLLOWS: inclusion body myopathy (mean onset at 42 years of age), Paget's disease
of the bone and FTD (mean onset at 55 years of age). It is mostly the behavioural
form of FTD (behavioural changes, executive dysfunction and aphasia). One
interesting finding in our report is the predominance of the psychiatric symptoms
at the beginning of the behavioural changes, which led to the diagnosis of FTD.
The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation
found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in
the VCP gene.
PMID- 24348399
TI - Multiple vascular accidents including rupture of a sinus of valsalva aneurysm, a
minor ischemic stroke and intracranial arterial anomaly in a patient with
systemic congenital abnormalities: a case report.
AB - A 39-year-old man with a history of rupture of a sinus of Valsalva aneurysm
experienced an ischemic stroke. Although the patient presented left-sided
hemiparesis for a week, no abnormal signals were indicated on diffusion-weighted
imaging with repeated magnetic resonance scans. Carotid ultrasound and cerebral
angiography were conducted, and they revealed hypoplasty of the left internal
carotid artery with a low-lying carotid bifurcation at the level of the C6
vertebra. In addition, he was diagnosed with intellectual disabilities, evaluated
by the Wechsler Adult Intelligence Scale-III, and congenital velopharyngeal
insufficiency. We herein present the first report of a patient with cardio
cerebrovascular abnormalities, intellectual disabilities, and an
otorhinolaryngological abnormality.
PMID- 24348400
TI - Does intrathecal baclofen have a place in the treatment of painful spasms in
friedreich ataxia?
AB - We present the case of a 50-year-old female patient with Friedreich ataxia (FA)
who was treated successfully with an intrathecal baclofen (ITB)-delivering pump
for painful spasms. To our knowledge, this is the second reported case of FA
where ITB relieved painful and disabling spasms. We suggest that ITB should be
considered in the treatment of disabling spasms in patients with FA.
PMID- 24348401
TI - Spontaneous Closure of a Full-Thickness Stage 2 Idiopathic Macular Hole without
Posterior Vitreous Detachment.
AB - OBJECTIVE: We report a 50-year-old female patient with a stage 2 idiopathic
macular hole that closed spontaneously. METHOD: The case is presented on the
basis of an observational case report. RESULTS: The stage 2 idiopathic macular
hole closed spontaneously in 6 weeks with a lamellar defect in the outer retina
due to the formation of the bridging retinal tissue, but without any evidence of
the common mechanisms of spontaneous closure such as posterior vitreous
detachment or epiretinal membrane formation.
PMID- 24348402
TI - Recurrent annular peripheral choroidal detachment after trabeculectomy.
AB - We report a challenging case of recurrent flat anterior chamber without hypotony
after trabeculectomy in a 54-year-old Black male with a remote history of steroid
treated polymyositis, cataract surgery, and uncontrolled open angle glaucoma. The
patient presented with a flat chamber on postoperative day 11, but had a normal
fundus exam and intraocular pressure (IOP). Flat chamber persisted despite
treatment with cycloplegics, steroids, and a Healon injection into the anterior
chamber. A transverse B-scan of the peripheral fundus revealed a shallow annular
peripheral choroidal detachment. The suprachoroidal fluid was drained. The
patient presented 3 days later with a recurrent flat chamber and an annular
peripheral choroidal effusion. The fluid was removed and reinforcement of the
scleral flap was performed with the resolution of the flat anterior chamber. A
large corneal epithelial defect developed after the second drainage. The oral
prednisone was tapered quickly and the topical steroid was decreased. One week
later, his vision decreased to count fingers with severe corneal stromal edema
and Descemet's membrane folds that improved to 20/50 within 24 h of resumption of
the oral steroid and frequent topical steroid. The patient's visual acuity
improved to 20/20 following a slow withdrawal of the oral and topical steroid.
Eight months after surgery, the IOP was 15 mm Hg without glaucoma medication. The
detection of a shallow anterior choroidal detachment by transverse B-scan is
critical to making the correct diagnosis. Severe cornea edema can occur if the
steroid is withdrawn too quickly. Thus, steroids should be tapered cautiously in
steroid-dependent patients.
PMID- 24348403
TI - Forme Fruste Keratoconus Imaging and Validation via Novel Multi-Spot Reflection
Topography.
AB - BACKGROUND/AIMS: This case report aims to evaluate safety, efficacy and
applicability of anterior surface imaging in a patient with forme fruste
keratoconus (FFKC) based on a novel multi-spot, multicolor light-emitting-diode
(LED) tear film-reflection imaging technology. CASE DESCRIPTION: A 45-year-old
male patient, clinically diagnosed with FFKC, with highly asymmetric
manifestation between his eyes, was subjected to the multicolor-spot reflection
topography. We investigated elevation and sagittal curvature maps comparatively
with the multicolor-spot reflection topographer, a Placido topographer and a
Scheimpflug imaging system. For the right eye, steep and flat keratometry values
were 41.92 and 41.05 D with the multicolor spot-reflection topographer, 42.30 and
42.08 D with the Placido, and 41.95 and 41.19 D with the Scheimpflug system. For
the left eye, steep and flat keratometry values were 41.86 and 41.19 D with the
multicolor spot-reflection topographer, 42.06 and 41.66 D with the Placido
topographer, and 41.96 and 41.66 D with the Scheimpflug camera. Average
repeatability of the keratometry measurements was +/-0.35 D for the multicolor
spot-reflection topographer, +/-0.30 D for the Placido, and +/-0.25 D for the
Scheimpflug camera. Very good agreement between the instruments was demonstrated
on the elevation and curvature maps. CONCLUSION: The ease of use and the
comparable results offered by the multicolor spot-reflection topographer, in
comparison to established Placido and Scheimpflug imaging, as well as the
increased predictability that may be offered by the multicolor spot-reflection
topographer, may hold promise for wider clinical application, such as screening
of young adults for early keratoconus and, in a much wider perspective, potential
candidates for laser corneal refractive surgery.
PMID- 24348404
TI - Traumatic partial aniridia and cataract after iris-fixated foldable phakic
intraocular lens implantation.
AB - We present the first case of partial aniridia, traumatic cataract, and
peripapillary subretinal hemorrhage after blunt trauma to an eye containing a
foldable iris-fixated phakic intraocular lens (pIOL). Although the patient
experienced visual loss because of considerable corneal astigmatism and a
traumatic cataract, vision was recovered by a 2-stage primary corneal repair and
cataract surgery with a toric intraocular lens. This case exhibits clinical
manifestations that differ from previously reported trauma of a non-foldable iris
fixated pIOL. A relatively small corneal incision and a large optic diameter of
Artiflex pIOLs may prevent posttraumatic total expulsion of intraocular tissues
and present different clinical features from the case of non-foldable pIOLs
(Artisan). Although the extent of the damage is different, the possibility of
aniridia and traumatic cataract exists in eyes with both foldable and non
foldable iris-fixated pIOLs.
PMID- 24348405
TI - Successful corticosteroid-sparing effect of rituximab in the treatment of
refractory idiopathic orbital inflammatory disease.
AB - Idiopathic orbital inflammatory disease (IOID) is an idiopathic inflammatory
process within the orbit that can result in permanent visual impairment. Although
high-dose oral corticosteroids are currently the mainstay of therapy, their long
term usage can cause significant toxicity. We present a case of IOID that was
successfully treated with the anti-CD20 monoclonal antibody rituximab following
failed steroid sparing with conventional second-line immunosuppressive agents.
PMID- 24348406
TI - Toric intraocular lens implantation for correction of astigmatism in cataract
patients with corneal ectasia.
AB - Our purpose was to examine the long-term efficacy of toric intraocular lens (IOL)
implantation in cataract patients with high astigmatism due to corneal ectasia,
who underwent phacoemulsification cataract surgery. Five eyes of 3 cataract
patients with topographically stable keratoconus or pellucid macular degeneration
(PMD), in which phacoemulsification with toric IOL implantation was used to
correct high astigmatism, are reported. Objective and subjective refraction,
visual acuity measurement and corneal topography were performed in all cases
before and after cataract surgery. In all cases, there was a significant
improvement in visual acuity, as well as refraction, which remained stable over
time. Specifically, in subjective refraction, all patients achieved visual acuity
from 7/10 to 9/10 with up to -2.50 cyl. Corneal topography also remained stable.
Postoperative follow-up was 18-28 months. Cataract surgery with toric IOL
implantation seems to be safe and effective in correcting astigmatism and
improving visual function in cataract patients with topographically stable
keratoconus or PMD.
PMID- 24348407
TI - Mobius syndrome: surgical treatment for eyelid dysfunction.
AB - INTRODUCTION: Mobius syndrome is a heterogeneous congenital disorder that is
linked to bilateral palsies of the cranial nerves VI and VII, resulting in
congenital facial paralysis sometimes associated with impaired ocular abduction.
CASE REPORT: We present the case of a 44-year-old woman with Mobius syndrome and
inferior recurrent keratitis secondary to scleral show in both eyes. We decided
to use a cartilage graft from the ear in the inferior eyelid to avoid eyelid
retraction and scleral show. DISCUSSION: Patients with Mobius syndrome have a
severe dysfunction of their facial mimic. Their treatment must be individualized,
depending on their age, clinical examination and symptoms.
PMID- 24348408
TI - Macroaneurysm on the optic disc in a patient with aortic dissection.
AB - PURPOSE: We report a case of macroaneurysm on the optic disc, a rare location,
accompanied by vitreous hemorrhage in a patient with aortic dissection. METHODS:
A 60-year-old female with a history of aortic dissection at the age of 51
presented with visual disturbance owing to vitreous hemorrhage in her right eye.
During vitrectomy, we found a large macroaneurysm on the optic disc that was
beating and oozing blood. However, the macroaneurysm was not treated. RESULTS:
The macroaneurysm gradually shrunk, and the beating and oozing of blood
disappeared accordingly. CONCLUSION: Up to now, there have been no reports of
macroaneurysm on the optic disc in aortic dissection patients. The association
between macroaneurysm on the optic disc and aortic dissection is unclear;
therefore, additional case reports may be necessary. To the best of our
knowledge, our case is the first one reported in the literature.
PMID- 24348409
TI - A simple and easy method using rigid endoscope to detect iridocorneal and
keratolenticular adhesions in peters' anomaly.
AB - Peters' anomaly is characterized by a central corneal opacity with corresponding
defects in the posterior stroma, Descemet's membrane, and endothelium. We present
2 cases that showed corneal opacity when examined by topical endoscopic imaging
(TEI). Case 1 was a 20-day-old neonatal female who had a central corneal opacity
in the left eye. TEI showed that the iris stroma was adhered toward the back of
the opacified cornea. Case 2 was a 4-month-old male who had a bilateral corneal
opacity. TEI revealed that both a keratolenticular adhesion and a surrounding
iridocorneal adhesion were observed behind the area of corneal opacity. The
patient was diagnosed as having Peters' anomaly with persistent fetal
vasculature. This study demonstrates that TEI is a novel method capable of
looking into an eye from only a small area of the clear cornea.
PMID- 24348410
TI - Floating vitreous cyst: two clinical cases.
AB - PURPOSE: To report two cases of solitary unilateral vitreous cyst. METHODS: A
complete ocular examination, fundus photography, B-scan ultrasound and spectral
domain optical coherence tomography were performed in both patients. RESULTS: The
first patient (a 39-year-old man) presented with transient blurred vision in the
right eye. The second patient (a 78-year-old man) reported transient blurred
vision in the right eye when changing head position. He was referred to the Eye
Hospital because of vitreomacular traction in the other eye. After examination, a
diagnosis of vitreous cyst was made in both cases. CONCLUSIONS: Vitreous cysts
are rare clinical findings. They can occur in normal eyes or in eyes with certain
ocular pathologies. When a cyst floats into the visual axis area, it can disturb
visual function; therefore, patients usually report transient blurring of vision.
A prompt clinical examination is necessary for differentiating this rare
condition.
PMID- 24348411
TI - Patient-Reported Difference following Implantation of a Blue Light-Filtering
Aspheric Intraocular Lens and a UV-Filtering Aspheric Intraocular Lens.
AB - We report on a series of 6 patients who experienced yellow vision after
uncomplicated cataract surgery in their second eye. In the first eye, an aspheric
blue-light filtering intraocular lens (IOL) was implanted, followed by the
implantation of a 1-Piece aspheric IOL in the second eye. The time between the
surgeries ranged from 12 months to 3 years. The patients experienced noticeable
differences between the yellow and the clear lens. It is suggested to avoid
mixing blue light-filtering and UV-filtering IOLs in the same patient,
particularly in those who have high expectations following cataract surgery.
PMID- 24348412
TI - Intraocular Invasion of Adult T-Cell Leukemia Cells without Systemic Symptoms
after Cataract Surgery.
AB - Adult T-cell leukemia (ATL) is an aggressive lymphoid proliferation associated
with the human T-lymphotropic virus type I (HTLV-I). The intraocular invasion of
ATL is a rare event. A 75-year-old man without any systemic disease underwent
uneventful cataract surgery of the right eye. On postoperative day 6, the patient
presented with blurred vision due to severe vitreous opacity in the right eye.
Analysis of the vitreous fluid revealed a suspected ATL infection based on the
flow cytometric analysis. Moreover, cytological examination of the vitreous
specimen revealed flower cell infiltration, and HTLV-1 DNA was detected by PCR
analysis of the vitreous sample. Monoclonal T-cell receptor chain rearrangement
was also detected by PCR. Thorough analysis of a vitreous sample is essential for
vitrectomy in vitreous opacity of unknown cause. Flow cytometric, cytological,
and PCR analysis of vitreous samples is beneficial for determining the cause of
this kind of severe illness.
PMID- 24348413
TI - Intracapsular lens extraction for the treatment of pupillary block glaucoma
associated with anterior subluxation of the crystalline lens.
AB - PURPOSE: To report a case of pupillary block glaucoma associated with spontaneous
crystalline lens subluxation into the anterior chamber in a 34-year-old man.
METHODS: Dry vitrectomy was performed for securing enough retrolental space, and
an intracapsular lens extraction was then performed via a corneolimbal incision.
Additional endothelial cell damage was avoided with an injection of viscoelastics
and gentle extraction of the crystalline lens. After deepening of the anterior
chamber, scleral fixation of the intraocular lens was performed with an ab
externo technique. RESULTS: Two months after the operation, a well-fixated
intraocular lens was observed and intraocular pressure was stable. The
postoperative corneal astigmatism was -3.5 dpt, and the patient had a best
corrected visual acuity of 20/25. Postoperative complications included decreased
endothelial cell count and sector iris paralysis near the incision site.
CONCLUSIONS: An anteriorly subluxated crystalline lens can cause pupillary block
glaucoma in healthy young adults. To prevent intraoperative complications,
intracapsular lens extraction with dry vitrectomy can be a good surgical option.
The endothelial cell density should be closely monitored after surgery.
PMID- 24348414
TI - Neuroretinitis with branch retinal artery occlusion in a 15-year-old female.
AB - We report a case of Bartonella henselae neuroretinitis with significant disc and
peripapillary edema, branch retinal artery occlusion without macula involvement
and well preserved central vision. A 15-year-old female presented with loss of
vision over 4 weeks in the left eye. She had a history of cat exposure, but a cat
scratch, insect bite or conjunctivitis was not reported. An inferotemporal
arcuate scotoma developed during the acute phase and persisted over the course of
the follow-up.
PMID- 24348415
TI - Methicillin-Resistant Staphylococcus aureus Keratitis after Descemet's Stripping
Automated Endothelial Keratoplasty.
AB - PURPOSE: We report a case of methicillin-resistant Staphylococcus aureus (MRSA)
keratitis after Descemet's stripping automated endothelial keratoplasty (DSAEK).
CASE REPORT: An 87-year-old woman who had undergone a DSAEK 4 months previously
was referred to Tokushima University Hospital with a diagnosis of infectious
keratitis after DSAEK. A white abscess and infiltration in the inferior cornea of
the right eye were observed. We started an empiric therapy using topical
levofloxacin and chloramphenicol on the basis of the microscopic findings of the
corneal scraping concurrently with cultivation of the cornea. RESULTS: A strain
of MRSA was isolated from the corneal sample. Although the strain was susceptible
to chloramphenicol, it was resistant to quinolone. The keratitis improved rapidly
due to empiric therapy, and topical steroids could be resumed 6 days after
initiation of the empiric therapy. CONCLUSIONS: To our knowledge, this is the
first case of MRSA keratitis, and the second case of bacterial keratitis, after
DSAEK. MRSA keratitis can occur following uneventful DSAEK. The empiric therapy
on the basis of results from a light microscopic examination of a Gram-stained
corneal scraping and restarting topical steroids in the early stages of
medication contributed to the good clinical course of this case.
PMID- 24348416
TI - Washout allometric reference method (WARM) for parametric analysis of [(11)C]PIB
in human brains.
AB - Rapid clearance and disappearance of a tracer from the circulation challenges the
determination of the tracer's binding potentials in brain (BP ND) by positron
emission tomography (PET). This is the case for the analysis of the binding of
radiolabeled [(11)C]Pittsburgh Compound B ([(11)C]PIB) to amyloid-beta (Abeta)
plaques in brain of patients with Alzheimer's disease (AD). To resolve the issue
of rapid clearance from the circulation, we here introduce the flow-independent
Washout Allometric Reference Method (WARM) for the analysis of washout and
binding of [(11)C]PIB in two groups of human subjects, healthy aged control
subjects (HC), and patients suffering from AD, and we compare the results to the
outcome of two conventional analysis methods. We also use the rapid initial
clearance to obtain a surrogate measure of the rate of cerebral blood flow (CBF),
as well as a method of identifying a suitable reference region directly from the
[(11)C]PIB signal. The difference of average absolute CBF values between the AD
and HC groups was highly significant (P < 0.003). The CBF measures were not
significantly different between the groups when normalized to cerebellar gray
matter flow. Thus, when flow differences confound conventional measures of
[(11)C]PIB binding, the separate estimates of CBF and BP ND provide additional
information about possible AD. The results demonstrate the importance of data
driven estimation of CBF and BP ND, as well as reference region detection from
the [(11)C]PIB signal. We conclude that the WARM method yields stable measures of
BP ND with relative ease, using only integration for noise reduction and no model
regression. The method accounts for relative flow differences in the brain tissue
and yields a calibrated measure of absolute CBF directly from the [(11)C]PIB
signal. Compared to conventional methods, WARM optimizes the Abeta plaque load
discrimination between patients with AD and healthy controls (P = 0.009).
PMID- 24348417
TI - Drive for consumption, craving, and connectivity in the visual cortex during the
imagery of desired food.
AB - There is considerable interest in understanding food cravings given the
obesogenic environment of Western Society. In this paper we examine how the
imagery of palatable foods affects cravings and functional connectivity in the
visual cortex for people who differ on the power of food scale (PFS). Fourteen
older, overweight/obese adults came to our laboratory on two different occasions.
Both times they ate a controlled breakfast meal and then were restricted from
eating for 2.5 h prior to scanning. On 1 day they consumed a BOOST((r)) liquid
meal after the period of food restriction, whereas on the other day they only
consumed water (NO BOOST((r)) condition). After these manipulations, they had an
fMRI scan in which they were asked to image both neutral objects and their
favorite snack foods; they also completed visual analog scales for craving,
hunger, and the vividness of the imagery experiences. Irrespective of the
BOOST((r)) manipulation, we observed marked increases in food cravings when
older, overweight/obese adults created images of favorite foods in their minds as
opposed to creating an image of neutral objects; however, the increase in food
craving following the imagery of desired food was more pronounced among those
scoring high than low on the PFS. Furthermore, local efficiency within the visual
cortex when imaging desired food was higher for those scoring high as compared to
low on the PFS. The active imagery of desired foods seemed to have overpowered
the BOOST((r)) manipulation when evaluating connectivity in the visual cortex.
PMID- 24348418
TI - Age-related changes in consolidation of perceptual and muscle-based learning of
motor skills.
AB - Improvements in motor sequence learning come about via goal-based learning of the
sequence of visual stimuli and muscle-based learning of the sequence of movement
responses. In young adults, consolidation of goal-based learning is observed
after intervals of sleep but not following wake, whereas consolidation of muscle
based learning is greater following intervals with wake compared to sleep. While
the benefit of sleep on motor sequence learning has been shown to decline with
age, how sleep contributes to consolidation of goal-based vs. muscle-based
learning in older adults (OA) has not been disentangled. We trained young (n =
62) and older (n = 50) adults on a motor sequence learning task and re-tested
learning following 12 h intervals containing overnight sleep or daytime wake. To
probe consolidation of goal-based learning of the sequence, half of the
participants were re-tested in a configuration in which the stimulus sequence was
the same but, due to a shift in stimulus-response mapping, the movement response
sequence differed. To probe consolidation of muscle-based learning, the remaining
participants were tested in a configuration in which the stimulus sequence was
novel, but now the sequence of movements used for responding was unchanged. In
young adults, there was a significant condition (goal-based vs. muscle-based
learning) by interval (sleep vs. wake) interaction, F(1,58) = 6.58, p = 0.013:
goal-based learning tended to be greater following sleep compared to wake, t(29)
= 1.47, p = 0.072. Conversely, muscle-based learning was greater following wake
than sleep, t(29) = 2.11, p = 0.021. Unlike young adults, this interaction was
not significant in OA, F(1,46) = 0.04, p = 0.84, nor was there a main effect of
interval, F(1,46) = 1.14, p = 0.29. Thus, OA do not preferentially consolidate
sequence learning over wake or sleep.
PMID- 24348420
TI - Gene expression of muscarinic, tachykinin, and purinergic receptors in porcine
bladder: comparison with cultured cells.
AB - Urothelial cells, myofibroblasts, and smooth muscle cells are important cell
types contributing to bladder function. Multiple receptors including muscarinic
(M3/M5), tachykinin (NK1/NK2), and purinergic (P2X1/P2Y6) receptors are involved
in bladder motor and sensory actions. Using female pig bladder, our aim was to
differentiate between various cell types in bladder by genetic markers. We
compared the molecular expression pattern between the fresh tissue layers and
their cultured cell counterparts. We also examined responses to agonists for
these receptors in cultured cells. Urothelial, suburothelial (myofibroblasts),
and smooth muscle cells isolated from pig bladder were cultured (10-14 days) and
identified by marker antibodies. Gene (mRNA) expression level was demonstrated by
real-time PCR. The receptor expression pattern was very similar between
suburothelium and detrusor, and higher than urothelium. The gene expression of
all receptors decreased in culture compared with the fresh tissue, although the
reduction in cultured urothelial cells appeared less significant compared to
suburothelial and detrusor cells. Cultured myofibroblasts and detrusor cells did
not contract in response to the agonists acetylcholine, neurokinin A, and
beta,gamma-MeATP, up to concentrations of 0.1 and 1 mM. The significant reduction
of M3, NK2, and P2X1 receptors under culture conditions may be associated with
the unresponsiveness of cultured suburothelial and detrusor cells to their
respective agonists. These results suggest that under culture conditions, bladder
cells lose the receptors that are involved in contraction, as this function is no
longer required. The study provides further evidence that cultured cells do not
necessarily mimic the actions exerted by intact tissues.
PMID- 24348421
TI - Cardioprotection by systemic dosing of thymosin beta four following ischemic
myocardial injury.
AB - Thymosin beta 4 (Tbeta4) was previously shown to reduce infarct size and improve
contractile performance in chronic myocardial ischemic injury via two phases of
action: an acute phase, just after injury, when Tbeta4 preserves ischemic
myocardium via antiapoptotic or anti-inflammatory mechanisms; and a chronic
phase, when Tbeta4 activates the growth of vascular or cardiac progenitor cells.
In order to differentiate between the effects of Tbeta4 during the acute and
during the chronic phases, and also in order to obtain detailed hemodynamic and
biomarker data on the effects of Tbeta4 treatment suitable for use in clinical
studies, we tested Tbeta4 in a rat model of chronic myocardial ischemia using two
dosing regimens: short term dosing (Tbeta4 administered only during the first 3
days following injury), and long term dosing (Tbeta4 administered during the
first 3 days following injury and also every third day until the end of the
study). Tbeta4 administered throughout the study reduced infarct size and
resulted in significant improvements in hemodynamic performance; however, chamber
volumes and ejection fractions were not significantly improved. Tbeta4
administered only during the first 3 days following injury tended to reduce
infarct size, chamber volumes and improve hemodynamic performance. Plasma
biomarkers of myocyte injury were significantly reduced by Tbeta4 treatment
during the acute injury period, and plasma ANP levels were significantly reduced
in both dosing groups. Surprisingly, neither acute nor chronic Tbeta4 treatment
significantly increased blood vessel density in peri-infarct regions. These
results suggest the following: repeated dosing may be required to achieve
clinically measureable improvements in cardiac function post-myocardial
infarction (MI); improvement in cardiac function may be observed in the absence
of a high degree of angiogenesis; and that plasma biomarkers of cardiac function
and myocardial injury are sensitive pharmacodynamic biomarkers of the effects of
Tbeta4.
PMID- 24348419
TI - Controversies about the enhanced vulnerability of the adolescent brain to develop
addiction.
AB - Adolescence, defined as a transition phase toward autonomy and independence, is a
natural time of learning and adjustment, particularly in the setting of long-term
goals and personal aspirations. It also is a period of heightened sensation
seeking, including risk taking and reckless behaviors, which is a major cause of
morbidity and mortality among teenagers. Recent observations suggest that a
relative immaturity in frontal cortical neural systems may underlie the
adolescent propensity for uninhibited risk taking and hazardous behaviors.
However, converging preclinical and clinical studies do not support a simple
model of frontal cortical immaturity, and there is substantial evidence that
adolescents engage in dangerous activities, including drug abuse, despite knowing
and understanding the risks involved. Therefore, a current consensus considers
that much brain development during adolescence occurs in brain regions and
systems that are critically involved in the perception and evaluation of risk and
reward, leading to important changes in social and affective processing. Hence,
rather than naive, immature and vulnerable, the adolescent brain, particularly
the prefrontal cortex, should be considered as prewired for expecting novel
experiences. In this perspective, thrill seeking may not represent a danger but
rather a window of opportunities permitting the development of cognitive control
through multiple experiences. However, if the maturation of brain systems
implicated in self-regulation is contextually dependent, it is important to
understand which experiences matter most. In particular, it is essential to
unveil the underpinning mechanisms by which recurrent adverse episodes of stress
or unrestricted access to drugs can shape the adolescent brain and potentially
trigger life-long maladaptive responses.
PMID- 24348422
TI - Adult spinal cord ependymal layer: a promising pool of quiescent stem cells to
treat spinal cord injury.
AB - Spinal cord injury (SCI) is a major health burden and currently there is no
effective medical intervention. Research performed over the last decade revealed
that cells surrounding the central canal of the adult spinal cord and forming the
ependymal layer acquire stem cell properties either in vitro or in response to
injury. Following SCI activated ependymal cells generate progeny cells which
migrate to the injury site but fail to produce the appropriate type of cells in
sufficient number to limit the damage, rendering this physiological response
mainly ineffective. Research is now focusing on the manipulation of ependymal
cells to produce cells of the oligodendrocyte lineage which are primarily lost in
such a situation leading to secondary neuronal degeneration. Thus, there is a
need for a more focused approach to understand the molecular properties of adult
ependymal cells in greater detail and develop effective strategies for guiding
their response during SCI.
PMID- 24348423
TI - Polarization of membrane associated proteins in the choroid plexus epithelium
from normal and slc4a10 knockout mice.
AB - The choroid plexus epithelium (CPE) has served as a model-epithelium for cell
polarization and transport studies and plays a crucial role for cerebrospinal
fluid (CSF) production. The normal luminal membrane expression of Na(+),K(+)
ATPase, aquaporin-1 and Na(+)/H(+) exchanger 1 in the choroid plexus is severely
affected by deletion of the slc4a10 gene that encodes the bicarbonate
transporting protein Ncbe/NBCn2. The causes for these deviations from normal
epithelial polarization and redistribution following specific gene knockout are
unknown, but may be significant for basic epithelial cell biology. Therefore, a
more comprehensive analysis of cell polarization in the choroid plexus is
warranted. We find that the cytoskeleton in the choroid plexus contains alphaI-,
alphaII-, betaI-, and betaII-spectrin isoforms along with the anchoring protein
ankyrin-3, most of which are mainly localized in the luminal membrane domain.
Furthermore, we find alpha-adducin localized near the plasma membranes globally,
but with only faint expression in the luminal membrane domain. In slc4a10
knockout mice, the abundance of beta1 Na(+),K(+)-ATPase subunits in the luminal
membrane is markedly reduced. Anion exchanger 2 abundance is increased in slc4a10
knockout and its anchor protein, alpha-adducin is almost exclusively found near
the basolateral domain. The alphaI- and betaI-spectrin abundances are also
decreased in the slc4a10 knockout, where the basolateral domain expression of
alphaI-spectrin is exchanged for a strictly luminal domain localization. E
cadherin expression is unchanged in the slc4a10 knockout, while small decreases
in abundance are observed for its probable adaptor proteins, the catenins.
Interestingly, the abundance of the tight junction protein claudin-2 is
significantly reduced in the slc4a10 knockouts, which may critically affect
paracellular transport in this epithelium. The observations allow the generation
of new hypotheses on basic cell biological paradigms that can be tested
experimentally in future studies.
PMID- 24348424
TI - The interplay between stress and physical activity in the prevention and
treatment of cardiovascular disease.
PMID- 24348426
TI - Simple silicone chamber system for in vitro three-dimensional skeletal muscle
tissue formation.
AB - Bioengineering skeletal muscle often requires customized equipment and intricate
casting techniques. One of the major hurdles when initially trying to establish
in vitro tissue engineered muscle constructs is the lack of consistency across
published methodology. Although this diversity allows for specialization
according to specific research goals, lack of standardization hampers comparative
efforts. Differences in cell type, number and density, variability in matrix and
scaffold usage as well as inconsistency in the distance between and type of
adhesion posts complicates initial establishment of the technique with
confidence. We describe an inexpensive, but readily adaptable silicone chamber
system for the generation of skeletal muscle constructs that can readily be
standardized and used to elucidate myoblast behavior in a three-dimensional
space. Muscle generation, regeneration and adaptation can also be investigated in
this model, which is more advanced than differentiated myotubes.
PMID- 24348427
TI - Assessing homing failure in honeybees exposed to pesticides: Guez's (2013)
criticism illustrates pitfalls and challenges.
PMID- 24348425
TI - Effects of exercise training on cardiovascular adrenergic system.
AB - In heart failure (HF), exercise has been shown to modulate cardiac sympathetic
hyperactivation which is one of the earliest features of neurohormonal
derangement in this syndrome and correlates with adverse outcome. An important
molecular alteration related to chronic sympathetic overstimulation in HF is
represented by cardiac beta-adrenergic receptor (beta-AR) dysfunction. It has
been demonstrated that exercise reverses beta-AR dysfunction by restoring cardiac
receptor membrane density and G-protein-dependent adenylyl cyclase activation. In
particular, several evidence indicate that exercise reduces levels of cardiac G
protein coupled receptor kinase-2 (GRK2) which is known to be involved in both
beta1-AR and beta2-AR dysregulation in HF. Similar alterations of beta-AR system
have been described also in the senescent heart. It has also been demonstrated
that exercise training restores adrenal GRK2/alpha-2AR/catecholamine (CA)
production axis. At vascular level, exercise shows a therapeutic effect on age
related impairment of vascular reactivity to adrenergic stimulation and restores
beta-AR-dependent vasodilatation by increasing vascular beta-AR responsiveness
and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is
thought to account for >50% of all cases of hypertension and a lack of balance
between parasympathetic and sympathetic modulation has been observed in
hypertensive subjects. Non-pharmacological, lifestyle interventions have been
associated with reductions in SNS overactivity and blood pressure in
hypertension. Several evidence have highlighted the blood pressure lowering
effects of aerobic endurance exercise in patients with hypertension and the
significant reduction in sympathetic neural activity has been reported as one of
the main mechanisms explaining the favorable effects of exercise on blood
pressure control.
PMID- 24348428
TI - Regulation of insect behavior via the insulin-signaling pathway.
AB - The insulin/insulin-like growth factor signaling (IIS) pathway is well
established as a critical regulator of growth and metabolic homeostasis across
the animal kingdom. Insulin-like peptides (ILPs), the functional analogs of
mammalian insulin, were initially discovered in the silkmoth Bombyx mori and
subsequently identified in many other insect species. Initial research focused on
the role of insulin signaling in metabolism, cell proliferation, development,
reproduction and aging. More recently however, increasing attention has been
given to the role of insulin in the regulation of neuronal function and behavior.
Here we review the role of insulin signaling in two specific insect behaviors:
feeding and locomotion.
PMID- 24348430
TI - Mechanisms of auditory verbal hallucination in schizophrenia.
AB - Recent work on the mechanisms underlying auditory verbal hallucination (AVH) has
been heavily informed by self-monitoring accounts that postulate defects in an
internal monitoring mechanism as the basis of AVH. A more neglected alternative
is an account focusing on defects in auditory processing, namely a spontaneous
activation account of auditory activity underlying AVH. Science is often aided by
putting theories in competition. Accordingly, a discussion that systematically
contrasts the two models of AVH can generate sharper questions that will lead to
new avenues of investigation. In this paper, we provide such a theoretical
discussion of the two models, drawing strong contrasts between them. We identify
a set of challenges for the self-monitoring account and argue that the
spontaneous activation account has much in favor of it and should be the default
account. Our theoretical overview leads to new questions and issues regarding the
explanation of AVH as a subjective phenomenon and its neural basis. Accordingly,
we suggest a set of experimental strategies to dissect the underlying mechanisms
of AVH in light of the two competing models.
PMID- 24348431
TI - Identity Formation, Marijuana and "The Self": A Study of Cannabis Normalization
among University Students.
AB - Over the past half-century, as use of marijuana has become more widespread in
Canadian society, there are indications of a normalizing process in societal
reactions and experiences of use. Among other research avenues, these trends
suggest a need for further exploration of young people's understandings of how
they make the choice to use or not and how decisions relate to presentation of
the self. This study draws on interviews with 30 undergraduates recruited from a
larger online survey of respondents at the University of Guelph, ON, Canada. In
probing their perceptions of the use of marijuana, we often found that
trying/using "pot" was the default option, whereas choosing not to use required
more conscious effort. With specific reference to Goffman's contribution to a
situated understanding of the self, our findings are interpreted with emphasis on
further theoretical development of the normalization thesis and on the role of
marijuana in identity formation among persons in the process of transition to
adulthood.
PMID- 24348429
TI - Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB
Regulated Intracellular Signaling Pathways.
AB - Bipolar disorder is a common, complex, and severe psychiatric disorder with
cyclical disturbances of mood and a high suicide rate. Here, we describe a family
with four siblings, three affected females and one unaffected male. The disease
course was characterized by early-onset bipolar disorder and co-morbid anxiety
spectrum disorders that followed the onset of bipolar disorder. Genetic risk
factors were suggested by the early onset of the disease, the severe disease
course, including multiple suicide attempts, and lack of adverse prenatal or
early life events. In particular, drug and alcohol abuse did not contribute to
the disease onset. Exome sequencing identified very rare, heterozygous, and
likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C,
GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among
all three affected family members but absent in the unaffected sibling and in
more than 200 controls. The genes encode proteins with significant regulatory
roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These
pathways are central to neuronal and synaptic plasticity, cognition, affect
regulation and response to chronic stress. In addition, proteins in these
pathways are the target of commonly used mood-stabilizing drugs, such as
tricyclic antidepressants, lithium, and valproic acid. The combination of
multiple rare, damaging mutations in these central pathways could lead to reduced
resilience and increased vulnerability to stressful life events. Our results
support a new model for psychiatric disorders, in which multiple rare, damaging
mutations in genes functionally related to a common signaling pathway contribute
to the manifestation of bipolar disorder.
PMID- 24348432
TI - Working memory capacity and psychotic-like experiences in a general population
sample of adolescents and young adults.
AB - Working memory (WM) impairment is a common feature in individuals with
schizophrenia and high-risk for psychosis and a promising target for early
intervention strategies. However, it is unclear to what extent WM impairment
parallels specific behavioral symptoms along the psychosis continuum. To address
this issue, the current study investigated the relation of WM capacity with
psychotic-like experiences (PLEs) in a large Swedish population sample (N = 1012)
of adolescents and young adults (M = 24.4 years, range 12-35). WM was assessed
with two online computer tasks: a task where participants had to identify and
remember the location of an odd shape and a task of remembering and following
instructions. PLE scores were derived from a translated symptom questionnaire
(Community Assessment of Psychic Experiences), which includes positive, negative,
and depressive symptom scales. Positive and negative symptom scales were further
subdivided into symptom clusters based on factor analyses. The results showed
that low WM capacity was modestly associated with increased reports of bizarre
experiences (BE) and depressive symptoms, after controlling for age, gender, and
global symptom scores. Interestingly, when analyses were repeated for separate
age groups, low WM was exclusively associated with a higher frequency of BE for
young adults (20-27 years) and with depressive symptoms for older adults (28-35
years). These findings suggest that specific PLEs can be indicative of reduced WM
capacity in early adulthood, which in turn may reflect an increased risk for
psychosis and a greater need for targeted intervention. In contrast, during
adolescence individual differences in cognitive development may influence the
strength of the relationships and thereby mask potential vulnerabilities for
psychopathology.
PMID- 24348434
TI - Toward understanding social cues and signals in human-robot interaction: effects
of robot gaze and proxemic behavior.
AB - As robots are increasingly deployed in settings requiring social interaction,
research is needed to examine the social signals perceived by humans when robots
display certain social cues. In this paper, we report a study designed to examine
how humans interpret social cues exhibited by robots. We first provide a brief
overview of perspectives from social cognition in humans and how these processes
are applicable to human-robot interaction (HRI). We then discuss the need to
examine the relationship between social cues and signals as a function of the
degree to which a robot is perceived as a socially present agent. We describe an
experiment in which social cues were manipulated on an iRobot Ava(TM) mobile
robotics platform in a hallway navigation scenario. Cues associated with the
robot's proxemic behavior were found to significantly affect participant
perceptions of the robot's social presence and emotional state while cues
associated with the robot's gaze behavior were not found to be significant.
Further, regardless of the proxemic behavior, participants attributed more social
presence and emotional states to the robot over repeated interactions than when
they first interacted with it. Generally, these results indicate the importance
for HRI research to consider how social cues expressed by a robot can
differentially affect perceptions of the robot's mental states and intentions.
The discussion focuses on implications for the design of robotic systems and
future directions for research on the relationship between social cues and
signals.
PMID- 24348433
TI - Narrative descriptions should replace grades and numerical ratings for clinical
performance in medical education in the United States.
AB - BACKGROUND: In medical education, evaluation of clinical performance is based
almost universally on rating scales for defined aspects of performance and scores
on examinations and checklists. Unfortunately, scores and grades do not capture
progress and competence among learners in the complex tasks and roles required to
practice medicine. While the literature suggests serious problems with the
validity and reliability of ratings of clinical performance based on numerical
scores, the critical issue is not that judgments about what is observed vary from
rater to rater but that these judgments are lost when translated into numbers on
a scale. As the Next Accreditation System of the Accreditation Council on
Graduate Medical Education (ACGME) takes effect, medical educators have an
opportunity to create new processes of evaluation to document and facilitate
progress of medical learners in the required areas of competence. Proposal and
initial experience: Narrative descriptions of learner performance in the clinical
environment, gathered using a framework for observation that builds a shared
understanding of competence among the faculty, promise to provide meaningful
qualitative data closely linked to the work of physicians. With descriptions
grouped in categories and matched to milestones, core faculty can place each
learner along the milestones' continua of progress. This provides the foundation
for meaningful feedback to facilitate the progress of each learner as well as
documentation of progress toward competence. IMPLICATIONS: This narrative
evaluation system addresses educational needs as well as the goals of the Next
Accreditation System for explicitly documented progress. Educators at other
levels of education and in other professions experience similar needs for
authentic assessment and, with meaningful frameworks that describe roles and
tasks, may also find useful a system built on descriptions of learner performance
in actual work settings. CONCLUSIONS: We must place medical learning and
assessment in the contexts and domains in which learners do clinical work. The
approach proposed here for gathering qualitative performance data in different
contexts and domains is one step along the road to moving learners toward
competence and mastery.
PMID- 24348435
TI - Numerical synesthesia is more than just a symbol-induced phenomenon.
PMID- 24348436
TI - Lexical neighborhood effects in pseudoword spelling.
AB - The general aim of this study is to contribute to a better understanding of the
cognitive processes that underpin skilled adult spelling. More specifically, it
investigates the influence of lexical neighbors on pseudo-word spelling with the
goal of providing a more detailed account of the interaction between lexical and
sublexical sources of knowledge in spelling. In prior research examining this
topic, adult participants typically heard lists composed of both words and pseudo
words and had to make a lexical decision to each stimulus before writing the
pseudo-words. However, these priming paradigms are susceptible to strategic
influence and may therefore not give a clear picture of the processes normally
engaged in spelling unfamiliar words. In our two Experiments involving 71 French
speaking literate adults, only pseudo-words were presented which participants
were simply requested to write to dictation using the first spelling that came to
mind. Unbeknownst to participants, pseudo-words varied according to whether they
did or did not have a phonological word neighbor. Results revealed that low
probability phoneme/grapheme mappings (e.g., /o/ -> aud in French) were used
significantly more often in spelling pseudo-words with a close phonological
lexical neighbor with that spelling (e.g., /krepo/ derived from "crapaud,"
/krapo/) than in spelling pseudo-words with no close neighbors (e.g., /fropo/).
In addition, the strength of this lexical influence increased with the lexical
frequency of the word neighbors as well as with their degree of phonetic overlap
with the pseudo-word targets. These results indicate that information from
lexical and sublexical processes is integrated in the course of spelling, and a
specific theoretical account as to how such integration may occur is introduced.
PMID- 24348437
TI - Using "Cinema Verite" (truthful cinema) to facilitate replication and
accountability in psychological research(?).
AB - To increase replication and accountability, it is proposed that researchers make
audio/video recordings of laboratory protocols using currently available
technologies, such as smart-phones. A detailed record of the procedure
representing each experimental condition of the study design with simulated
participants could then be posted on the internet and made accessible to
researchers wanting more information about the procedures described in the
research publication. Making recordings of all research participants a standard
practice would be a greater challenge because of threats to internal validity and
ethical concerns, however it is feasible and merits a broad discussion among
researchers, professional societies, IRB's and funding organizations.
PMID- 24348438
TI - Does interoceptive awareness affect the ability to regulate unfair treatment by
others?
AB - In this study we aimed to investigate how awareness of bodily responses, referred
to as interoceptive awareness, influences decision-making in a social interactive
context. Interoceptive awareness is thought to be crucial for adequate regulation
of one's emotions. However, there is a dearth of studies that examine the
association between interoceptive awareness and the ability to regulate emotions
during interpersonal decision-making. Here, we quantified interoceptive awareness
with a heartbeat detection task in which we measured the difference between
subjective self-reports and an objective psychophysiological measurement of
participant heart rates. Social decision-making was quantified using a two-round
Ultimatum Game. Participants were asked to first reject or accept an unfair
division of money proposed by a partner. In turn, participants could then make an
offer on how to divide an amount of money with the same partner. Participants
performed 20 rounds of the two-round Ultimatum Game twice, once during baseline
condition and once while asked to reappraise emotional reactions when confronted
with unfair offers from partners. Results showed that after reappraisal
participants (1) accepted more unfair offers and (2) offered higher return
divisions, as compared to baseline. With respect to interoceptive awareness,
participants with better heartbeat detection scores tended to report less
emotional involvement when they applied reappraisal while playing the Ultimatum
Game. However, there was no reliably significant relationship between heartbeat
detection and the acceptance of unfair offers. Similarly, heartbeat detection
accuracy was not related to return offers made in the second round of the
Ultimatum Game or the habitual use of emotion regulation. These preliminary
findings suggest that the relationship between interoceptive awareness and
behavioral changes due to emotion regulation in a social decision-making context
appears to be complex.
PMID- 24348439
TI - Sensory motor mechanisms unify psychology: the embodiment of culture.
AB - Sensorimotor mechanisms can unify explanations at cognitive, social, and cultural
levels. As an example, we review how anticipated motor effort is used by
individuals and groups to judge distance: the greater the anticipated effort the
greater the perceived distance. Anticipated motor effort can also be used to
understand cultural differences. People with interdependent self- construals
interact almost exclusively with in-group members, and hence there is little
opportunity to tune their sensorimotor systems for interaction with out-group
members. The result is that interactions with out-group members are expected to
be difficult and out-group members are perceived as literally more distant. In
two experiments we show (a) interdependent Americans, compared to independent
Americans, see American confederates (in-group) as closer; (b) interdependent
Arabs, compared to independent Arabs, perceive Arab confederates (in- group) as
closer, whereas interdependent Americans perceive Arab confederates (out-group)
as farther. These results demonstrate how the same embodied mechanism can
seamlessly contribute to explanations at the cognitive, social, and cultural
levels.
PMID- 24348440
TI - Socio-emotional correlates of a schooldog-teacher-team in the classroom.
AB - A growing number of teachers in Europe regularly take their dogs with them into
the classroom. Limited research points at positive socio-emotional effects of
this practice. In this study the effects of a schooldog-teacher-team on
socioemotional experiences in school, depression and emotion regulation
strategies were investigated in a classroom of third-graders (male n = 12, female
n = 13), which had a schooldog present for 1 day per week in comparison with a
control class (male n = 11, female n = 10). In contrast to the control class, the
dog-class students reported a stronger improvement with regard to positive
attitude toward school (repeated measures ANOVA; F = 10.769, df = 1, p = 0.002)
and positive emotions related to learning (F = 4.479, df = 1, p = 0.042) over the
course of the year. Since a prerequisite of all kinds of effective learning is a
positive attitude and mood toward school and learning, the presence of a
schooldog-teacher team thus has the potential to support learning.
PMID- 24348441
TI - The relationship of sex and sexual orientation to self-esteem, body shape
satisfaction, and eating disorder symptomatology.
AB - There is increasing interest in understanding what role, if any, sex and sexual
orientation play in body dissatisfaction, its correlates to distress, and its
relationship to disordered eating. The goals of the present study were to
examine: (a) differences in sex and sexual orientation in internalization of
societal pressure to modify physical appearance, components of body image
dissatisfaction, self-esteem, and eating disorder symptomatology and (b) whether
the internalization-eating disorder symptomatology was mediated by the different
components of body image dissatisfaction and low self-esteem. The present data
support several key trends in the literature: men generally reported less body
dissatisfaction, internalization of socio-cultural standards of beauty, drive for
thinness, and disordered eating, but a greater drive for muscularity than women;
results also indicated that different components of body image dissatisfaction
and low self-esteem partially mediated the relationship between internalization
and eating disorder symptomatology. Gay men reported significantly more body
dissatisfaction, internalization, eating disorder symptomatology, drive for
thinness, and drive for muscularity than heterosexual men. Compared to
heterosexual women, lesbians reported increased drive for muscularity, lower self
esteem, and lower internalization; however, they did not significantly differ on
body dissatisfaction, drive for thinness or disordered eating. Correlation
coefficients between body shape dissatisfaction and several aspects of mental
distress were significantly larger for gay men than heterosexual men; the same
coefficients did not differ between lesbian women and heterosexual women. Results
of path analyses indicated that the relationship between internalization and
disordered eating differs for gay and heterosexual men but not for lesbian and
heterosexual women. These results call attention to lesbians as a generally
understudied population.
PMID- 24348442
TI - Modulating mind-wandering in dysphoria.
AB - Depression is associated with significant difficulty staying "in the moment" as
the mind tends to wander away from current activity to focus instead on personal
concerns. Mind-wandering (MW) may in some instances be a precursor for depressive
rumination, a thinking style believed to confer vulnerability to the likelihood
and extent of depression. Thus, MW may be not only a consequence but also a cause
of low mood. Identifying a paradigm that could modulate MW, particularly in
depressed individuals, would allow future studies to test whether elevated rates
of MW causally drive cognitive-affective features of depression, such as
rumination and anhedonia. This study therefore explored the feasibility of using
an existing task manipulation to modulate behavioral and self-report indices of
MW in participants with varying levels of self-reported dysphoria. Participants
completed two go/no-go tasks-the SART and a high target probability task-and
measures of state and trait MW. The two tasks were identical in all respects
apart from the lower probability of no-go targets on the SART, a feature
considered to encourage mindless, or inattentive, responding. Across
participants, errors of commission (a behavioral indicator of MW) were elevated
on the SART relative to the high probability task, a pattern that was
particularly pronounced in dysphoric participants. Dysphoric individuals
furthermore reported elevated levels of MW, though the modulation of these
subjective reports by task was present to a similar rather than greater extent in
the dysphoric individuals. These findings provide encouraging preliminary support
for the use of this paradigm as one that modulates MW in depressed individuals.
The implications of these results and directions for future research are
discussed.
PMID- 24348443
TI - Rethinking the portrayal of deaf characters in children's picture books.
PMID- 24348444
TI - The way we encounter reading material influences how frequently we mind wander.
AB - We examined whether different encounters of reading material influence the
likelihood of mind wandering, memory for the material, and the ratings of
interest in the material. In a within-subjects design participants experienced
three different reading encounters: (1) reading a passage aloud, (2) listening to
a passage being read to them, and (3) reading a passage silently. Throughout each
reading encounter probes were given in order to identify mind wandering. After
finishing the passage participants also rated how interesting it was and
completed a content recognition test. Results showed that reading aloud led to
the least amount of mind wandering, while listening to the passage led to the
most mind wandering. Listening to the passage was also associated with the
poorest memory performance and the least interest in the material. Finally,
within the silent reading and listening encounters we observed negative relations
between mind wandering and both memory performance and interest in the material,
replicating previous findings. Taken together, the present findings improve our
understanding of the nature of mind wandering while reading, and have potentially
important implications for readers seeking to take advantage of the convenience
of audiobooks and podcasts.
PMID- 24348445
TI - Understanding egorrhea from cultural-clinical psychology.
AB - Based on his observations in Japanese clinical settings, Fujinawa (1972)
conceptualized egorrhea syndrome, which includes symptoms such as erythrophobia,
fear of eye-to-eye confrontation, olfactory reference syndrome, delusions of
soliloquy, delusions of sleep talking, and thought broadcasting. The key feature
of this syndrome is self-leakage, a perceived sense that one's personal internal
information, such as feelings and thoughts, are leaking out. To reach a more
comprehensive understanding of egorrhea, this paper aims to present general
overview and reconsider the phenomenon of self-leakage using cultural-clinical
psychology as a framework. First, the symptoms of egorrhea are reviewed in
relation to other related psychopathologies such as social anxiety disorder (SAD)
and taijin kyofusho (TKS), as well as schizophrenia. Second, a series of
empirical studies conducted using Japanese non-clinical samples are summarized.
The results of these studies form the basis for subsequent discussions, which
incorporates the cultural-clinical psychology perspective proposed by Ryder et
al. (2011). This paper ends with a general discussion regarding implications for
research and clinical practice.
PMID- 24348446
TI - Individuality in harpsichord performance: disentangling performer- and piece
specific influences on interpretive choices.
AB - Although a growing body of research has examined issues related to individuality
in music performance, few studies have attempted to quantify markers of
individuality that transcend pieces and musical styles. This study aims to
identify such meta-markers by discriminating between influences linked to
specific pieces or interpretive goals and performer-specific playing styles,
using two complementary statistical approaches: linear mixed models (LMMs) to
estimate fixed (piece and interpretation) and random (performer) effects, and
similarity analyses to compare expressive profiles on a note-by-note basis across
pieces and expressive parameters. Twelve professional harpsichordists recorded
three pieces representative of the Baroque harpsichord repertoire, including
three interpretations of one of these pieces, each emphasizing a different
melodic line, on an instrument equipped with a MIDI console. Four expressive
parameters were analyzed: articulation, note onset asynchrony, timing, and
velocity. LMMs showed that piece-specific influences were much larger for
articulation than for other parameters, for which performer-specific effects were
predominant, and that piece-specific influences were generally larger than
effects associated with interpretive goals. Some performers consistently deviated
from the mean values for articulation and velocity across pieces and
interpretations, suggesting that global measures of expressivity may in some
cases constitute valid markers of artistic individuality. Similarity analyses
detected significant associations among the magnitudes of the correlations
between the expressive profiles of different performers. These associations were
found both when comparing across parameters and within the same piece or
interpretation, or on the same parameter and across pieces or interpretations.
These findings suggest the existence of expressive meta-strategies that can
manifest themselves across pieces, interpretive goals, or expressive devices.
PMID- 24348447
TI - Sensory descriptors, hedonic perception and consumer's attitudes to Sangiovese
red wine deriving from organically and conventionally grown grapes.
AB - In recent years, produce obtained from organic farming methods (i.e., a system
that minimizes pollution and avoids the use of synthetic fertilizers and
pesticides) has rapidly increased in developed countries. This may be explained
by the fact that organic food meets the standard requirements for quality and
healthiness. Among organic products, wine has greatly attracted the interest of
the consumers. In the present study, trained assessors and regular wine consumers
were respectively required to identify the sensory properties (e.g., odor, taste,
flavor, and mouthfeel sensations) and to evaluate the hedonic dimension of red
wines deriving from organically and conventionally grown grapes. Results showed
differences related mainly to taste (sour and bitter) and mouthfeel (astringent)
sensations, with odor and flavor playing a minor role. However, these differences
did not influence liking, as organic and conventional wines were hedonically
comparable. Interestingly, 61% of respondents would be willing to pay more for
organically produced wines, which suggests that environmentally sustainable
practices related to wine quality have good market prospects.
PMID- 24348448
TI - Erratum: Early ERP signature of hearing impairment in visual rhyme judgment.
AB - [This corrects the article on p. 241 in vol. 4, PMID: 23653613.].
PMID- 24348449
TI - Staying and shifting patterns across IGT trials distinguish children with
externalizing disorders from controls.
AB - The Iowa Gambling Task (IGT) is the most widely instrument used in the assessment
of affective decision-making in several populations with frontal impairment. The
standard performance measure on the IGT is obtained by calculating the difference
between the advantageous and the disadvantageous choices. This standard score
does not allows the assessment of the use of different strategies to deal with
contingencies of gain and losses across the task. This study aims to compare the
standard score method used in IGT with a method that analyses the patterns of
staying and shifting among different decks across the 100 choices, considering
contingencies of choices with and without losses. We compared the IGT performance
of 24 children with externalizing disorders (Attention Deficit Hyperactivity
Disorder and Oppositional Defiant Disorder) and 24 healthy age-matched children.
The analyses of the standard score across all blocks failed to show differences
among children with externalizing disorders and control children. However,
healthy children showed a pattern of shifting more from disadvantageous decks to
advantageous decks and choosing more consecutive cards from the advantageous
decks across all blocks, independently of the contingency of losses. On the other
hand, children with externalizing disorders presented a pattern of shifting more
from advantageous decks to disadvantageous ones in comparison to healthy children
and repeatedly chose cards from the B deck across all blocks. This findings show
that even though differences among groups might not be found when using the
standard analyses, a different type of analysis might be able to show distinct
strategies on the execution of the test.
PMID- 24348451
TI - Erratum: Neural entrainment to rhythmically-presented auditory, visual and audio
visual speech in children.
AB - [This corrects the article on p. 216 in vol. 3, PMID: 22833726.].
PMID- 24348450
TI - Relationships between personality traits and attitudes toward the sense of smell.
AB - Olfactory perception appears to be linked to personality traits. This study aimed
to determine whether personality traits influence human attitudes toward sense of
smell. Two-hundred participants' attitudes toward their senses of smell and their
personality traits were measured using two self-administered questionnaires: the
Importance of Olfaction Questionnaire and the Eysenck Personality Questionnaire
Revised. Demographics and olfactory function were also assessed using a self
administered questionnaire. Gender-induced differences were present in attitudes
toward sense of smell. Women participants were more dependent than men
participants on olfactory cues for daily decision-making. In addition, as
participants evaluated their own olfactory functions more positively, they relied
more on olfactory information in everyday life. To determine a relationship
between personality traits and attitudes toward sense of smell, Spearman partial
correlation analyses were conducted, with controlling the factors that might
influence attitudes with respect to sense of smell (i.e., gender and self
awareness of olfactory function) as covariates. Participants who scored high on
the lie-scale (i.e., socially desirable and faking good), tended to use olfactory
cues for daily decision-making related both to social communication and product
purchase. In conclusion, our findings demonstrate a significant association
between personality traits and attitudes toward sense of smell.
PMID- 24348452
TI - A mid-level explanation for the venetian blind effect.
PMID- 24348453
TI - Alexithymia and fibromyalgia: clinical evidence.
AB - This review proposes a critical discussion of the latest studies investigating
the presence of alexithymia in patients with fibromyalgia (FM) and its relation
to other psychological disorders. The focus is on the most relevant literature
exploring the relationship between FM, a chronic pain syndrome, and alexithymia,
an affective dysregulation, largely observed in psychosomatic diseases. The
articles were selected from the Medline/Pubmed database using the search terms
"Fibromyalgia," "Alexithymia," and "Psychological Distress." Of the seven studies
fulfilling these criteria, one found no differences between FM patients and the
control group, four found significant differences, with higher levels of
alexithymia in the FM sample, while two showed unclear results. Overall, the
majority of findings highlighted the high prevalence of alexithymia in FM
patients. Future studies should clarify the role of alexithymia in FM, paying
attention to two principal aspects: the use, as a control group, of patients with
chronic pain conditions but a low psychosomatic component, and the use of other
measures, in addition to the Toronto Alexithymia Scale (TAS-20), to assess
alexithymia.
PMID- 24348454
TI - Influence of music on steroid hormones and the relationship between receptor
polymorphisms and musical ability: a pilot study.
AB - Studies have shown that music confers plasticity to the brain. In a preliminary
pilot study, we examined the effect of music listening on steroid hormones and
the relationship between steroid hormone receptor polymorphisms and musical
ability. Twenty-one subjects (10 males and 11 females) were recruited and divided
into musically talented and control groups. The subjects selected (1) music they
preferred (chill-inducing music) and (2) music they did not like. Before and
after the experiments, saliva was collected to measure the levels of steroid
hormones such as testosterone, estradiol, and cortisol. DNA was also isolated
from the saliva samples to determine the androgen receptor (AR) and arginine
vasopressin receptor 1A genotypes. Advanced Measures of Music Audiation (AMMA)
was used to determine the musical ability of the subjects. With both types of
music, the cortisol levels decreased significantly in both sexes. The
testosterone (T) levels declined in males when they listened to both types of
music. In females, the T levels increased in those listening to chill-inducing
music but declined when they listened to music they disliked. However, these
differences were not significant. The 17-beta estradiol levels increased in males
with both types of music, whereas the levels increased with chill-inducing music
but declined with disliked music in females. The AMMA scores were higher for the
short repeat length-type AR than for the long repeat length-type. Comparisons of
AR polymorphisms and T levels before the experiments showed that the T levels
were within the low range in the short repeat length-type group and there was a
positive relationship with the repeat length, although it was not significant.
This is the first study conducted in humans to analyze the relationships between
the AR gene, T levels, and musical ability.
PMID- 24348456
TI - No evidence for a role of competitive capabilities of adults in causing habitat
segregation of diploid and hexaploid Senecio carniolicus (Asteracaeae).
AB - Hexaploid individuals of Senecio carniolicus (Asteraceae) predominantly occur in
dense swards while diploids prevail in open vegetation. We test whether this
habitat segregation is due to differential responses to competition. Linear
regression models were used to relate biomass and maximum leaf length of adults
to vegetation cover within radii of 20 cm around target individuals. Biomass
differed between ploidy levels, but was independent from vegetation cover in both
cytotypes. Maximum leaf length of diploids increased with vegetation cover, but
remained constant in hexaploids. This suggests that at the adult stage diploids
respond to increasing competition by changes in plant architecture rather than
changes in resource utilization, while hexaploids are unaffected by competition.
Consequently, other factors, such as competitive interactions at earlier life
stages, likely are responsible for habitat segregation of diploid and hexaploid
S. carniolicus.
PMID- 24348455
TI - Alterations in the sense of time, space, and body in the mindfulness-trained
brain: a neurophenomenologically-guided MEG study.
AB - Meditation practice can lead to what have been referred to as "altered states of
consciousness."One of the phenomenological characteristics of these states is a
joint alteration in the sense of time, space, and body. Here, we set out to study
the unique experiences of alteration in the sense of time and space by
collaborating with a select group of 12 long-term mindfulness meditation (MM)
practitioners in a neurophenomenological setup, utilizing first-person data to
guide the neural analyses. We hypothesized that the underlying neural activity
accompanying alterations in the sense of time and space would be related to
alterations in bodily processing. The participants were asked to volitionally
bring about distinct states of "Timelessness" (outside time) and "Spacelessness"
(outside space) while their brain activity was recorded by MEG. In order to rule
out the involvement of attention, memory, or imagination, we used control states
of "Then" (past) and "There" (another place). MEG sensors evidencing alterations
in power values were identified, and the brain regions underlying these changes
were estimated via spatial filtering (beamforming). Particularly, we searched for
similar neural activity hypothesized to underlie both the state of "Timelessness"
and "Spacelessness." The results were mostly confined to the theta band, and
showed that: (1) the "Then"/"There" overlap yielded activity in regions related
to autobiographic memory and imagery (right posterior parietal lobule (PPL),
right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2)
"Timelessness"/"Spacelessness" conditions overlapped in a different network,
related to alterations in the sense of the body (posterior cingulate, right
temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided
neural analyses enabled us to dissociate different levels of alterations in the
sense of the body. This study illustrates the utility of employing experienced
contemplative practitioners within a neurophenomenological setup for
scientifically characterizing a self-induced altered sense of time, space and
body, as well as the importance of theta activity in relation with these altered
states.
PMID- 24348457
TI - Sleep Apnea and Inflammation - Getting a Good Night's Sleep with Omega-3
Supplementation.
AB - Obstructive sleep apnea (OSA) is a multifactorial sleep disorder associated with
an increased risk of cardiovascular mortality and morbidity. Several mechanisms
have been proposed to explain the association between OSA and cardiovascular
dysfunction. One of the proposed mechanisms is an inflammatory response to OSA
mediated by tumor necrosis factor (TNF-alpha). Patients with OSA have higher
plasma, serum, and intracellular levels of TNF-alpha, which may be reduced after
apnea treatment with continuous positive airway pressure (CPAP). Because TNF
alpha plays an important role in OSA related cardiovascular morbidity, the
present review aims to identify other preventive measures, in addition to CPAP,
that may minimize the inflammatory process in OSA and consequently the risk of
premature death due to cardiovascular dysfunction. Thus, we hypothesized that a
nutritional immunology profile, i.e., supplementation with omega-3 fatty acids,
may be valuable for individuals with OSA.
PMID- 24348458
TI - The cell and molecular biology of neurodegenerative diseases: an overview.
PMID- 24348459
TI - Neurobehavioral effects of levetiracetam in patients with traumatic brain injury.
AB - Moderate to severe traumatic brain injury (TBI) is one of the leading causes of
acquired epilepsy. Prophylaxis for seizures is the standard of care for
individuals with moderate to severe injuries at risk for developing seizures,
though relatively limited comparative data is available to guide clinicians in
their choice of agents. There have however been experimental studies which
demonstrate potential neuroprotective qualities of levetiracetam after TBI, and
in turn there is hope that eventually such agents may improve neurobehavioral
outcomes post-TBI. This mini-review summarizes the available studies and suggests
areas for future studies.
PMID- 24348460
TI - Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of
Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study.
AB - Co-heritability of hypertension and insulin resistance (IR) within families not
only implies genetic susceptibility may be responsible for these complex traits
but also suggests a rational that biological candidate genes for hypertension may
serve as markers for features of the metabolic syndrome (MetS). Thus we
determined whether the T323C polymorphism (rs5333) of endothelin type A (ETA)
receptor, a predominant receptor evoking potent vasoconstrictive action of
endothelin-1, contributes to susceptibility to IR-associated hypertension in 1694
subjects of Chinese and Japanese origins. Blood pressures (BPs) and
biochemistries were measured. Fasting insulin level, insulin-resistance
homeostasis model assessment (HOMAIR) score, and area under curve of insulin
concentration (AUCINS) were selected for assessing insulin sensitivity. Genotypes
were obtained by methods of polymerase chain reaction-restriction fragment length
polymorphism. Foremost findings were that minor allele frequency of the T323C
polymorphism was noticeable lower in our overall Asian subjects compared to multi
national population reported in gene database; moreover both the genotypic and
allelic frequencies of the polymorphism were significantly different between the
two ethnic groups we studied. The genotype distributions at TT/TC/CC were 65, 31,
4% in Chinese and 51, 41, 8% in Japanese, respectively (p < 0.0001).
Additionally, carriers of the C homozygote revealed characteristics of IR, namely
significantly higher levels of fasting insulin, HOMAIR score, and AUCINS at 29.3,
35.3, and 39.3%, respectively, when compared to their counterparts with TT/TC
genotypes in Chinese. Meanwhile, the CC genotype was associated with a higher
level of high density lipoprotein cholesterol in Japanese. No association of the
polymorphism with BP was observed. This study demonstrated for the first time
that T323C polymorphism of ETA receptor gene was associated with an adverse
insulin response in Chinese and a favorite atherogenic index in Japanese.
PMID- 24348461
TI - The multiplicity of post-translational modifications in pro-opiomelanocortin
derived peptides.
AB - The precursor protein, pro-opiomelanocortin (POMC) undergoes extensive post
translational processing in a tissue-specific manner to yield various
biologically active peptides involved in diverse cellular functions. The recently
developed method of matrix-assisted laser desorption/ionization mass spectrometry
(MALDI-MS) for direct tissue analysis has proved to be a powerful tool for
investigating the distribution of peptides and proteins. In particular,
topological mass spectrometry analysis using MALDI-MS can selectively provide a
mass profile of the hormones included in cell secretory granules. An advantage of
this technology is that it is possible to analyze a frozen thin slice section,
avoiding an extraction procedure. Subsequently, tandem mass spectrometry (MS/MS)
has a profound impact on addressing the modified residues in the hormone
molecules. Based on these strategies with mass spectrometry, several interesting
molecular forms of POMC-derived peptides have been found in the fish pituitary,
such as novel sites of acetylation in alpha-melanocyte-stimulating hormone (MSH),
hydroxylation of a proline residue in beta-MSH, and the phosphorylated form of
corticotropin-like intermediate lobe peptide.
PMID- 24348463
TI - Thrombospondin-1 Silencing Down-Regulates Integrin Expression Levels in Human
Anaplastic Thyroid Cancer Cells with BRAF(V600E): New Insights in the Host Tissue
Adaptation and Homeostasis of Tumor Microenvironment.
AB - BACKGROUND AND RATIONALE: Anaplastic thyroid cancer (ATC) is characterized by
pleomorphic cells, has a poor prognosis, is highly devastating disease, and is
not curable. No reliable biomarkers of metastatic potential, helpful for early
diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1
(TSP-1) plays a fundamental role in cancer progression by regulating cell stromal
cross-talk in the tumor microenvironment. GOALS: Our goal was to understand
whether TSP-1 could affect protein levels of its integrin receptors (e.g.,
ITGalpha3, alpha6, and beta1) and cell morphology in BRAF(V600E)-ATC cells in
vitro and in vivo. EXPERIMENTAL DESIGN: Anaplastic thyroid cancer-derived cell
cultures and western blotting were used to assess integrin protein expression
upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary
human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein
expression levels. RESULTS: TSP-1 knock-down down-regulates ITGalpha3, alpha6,
and beta1 in BRAF(V600E)-human ATC cells. BRAF(V600E)-ATC cells with TSP-1 knock
down were rounded compared to control cells, which displayed a spread morphology.
TSP-1 knock-down also reduced TSP-1, ITGalpha3, alpha6, and beta1 protein
expression levels in vivo in the ATC microenvironment, which is enriched in
stromal and inflammatory cells. CONCLUSION: TSP-1 silencing causes changes in ITG
levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might
contribute to earlier metastatic potential of BRAF(V600E)-positive aggressive
thyroid cancers, and allow improved patient selection for clinical trials.
PMID- 24348462
TI - Normal glucose metabolism in carnivores overlaps with diabetes pathology in non
carnivores.
AB - Carnivores, such as the dolphin and the domestic cat, have numerous adaptations
that befit consumption of diets with high protein and fat content, with little
carbohydrate content. Consequently, nutrient metabolism in carnivorous species
differs substantially from that of non-carnivores. Important metabolic pathways
known to differ between carnivores and non-carnivores are implicated in the
development of diabetes and insulin resistance in non-carnivores: (1) the hepatic
glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may
result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone
to periods of fasting hyperglycemia and exhibit insulin resistance, both of which
are risk factors for diabetes in non-carnivores. Similarly, carnivores develop
naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and
diabetes that have strong parallels with the same disorders in humans.
Understanding how evolution, environment, diet, and domestication may play a role
with nutrient metabolism in the dolphin and cat may also be relevant to human
diabetes.
PMID- 24348464
TI - Functional gene pyrosequencing and network analysis: an approach to examine the
response of denitrifying bacteria to increased nitrogen supply in salt marsh
sediments.
AB - Functional gene pyrosequencing is emerging as a useful tool to examine the
diversity and abundance of microbes that facilitate key biogeochemical processes.
One such process, denitrification, is of particular importance because it
converts fixed nitrate (NO(-) 3) to N2 gas, which returns to the atmosphere. In
nitrogen limited salt marshes, removal of NO(-) 3 prior to entering adjacent
waters helps prevent eutrophication. Understanding the dynamics of salt marsh
microbial denitrification is thus imperative for the maintenance of healthy
coastal ecosystems. We used pyrosequencing of the nirS gene to examine the
denitrifying community response to fertilization in experimentally enriched marsh
plots. A key challenge in the analysis of sequence data derived from
pyrosequencing is understanding whether small differences in gene sequences are
ecologically meaningful. We applied a novel approach from information theory to
determine that the optimal similarity level for clustering DNA sequences into
OTUs, while still capturing the ecological complexity of the system, was 88%.
With this clustering, phylogenetic analysis yielded 6 dominant clades of
denitrifiers, the largest of which, accounting for more than half of all the
sequences collected, had no close cultured representatives. Of the 638 OTUs
identified, only 11 were present in all plots and no single OTU was dominant. We
did, however, find a large number of specialist OTUs that were present only in a
single plot. The high degree of endemic OTUs, while accounting for a large
proportion of the nirS diversity in the plots, were found in lower abundance than
the generalist taxa. The proportion of specialist taxa increased with increasing
supply of nutrients, suggesting that addition of fertilizer may create conditions
that expand the niche space for denitrifying organisms and may enhance the
genetic capacity for denitrification.
PMID- 24348465
TI - Vibrio cholerae O1 epidemic variants in Angola: a retrospective study between
1992 and 2006.
AB - Cholera is still a major public health concern in many African countries. In
Angola, after a decade of absence, cholera reemerged in 1987, spreading
throughout the country until 1996, with outbreaks recurring in a seasonal
pattern. In 2006 Angola was hit by one of the most severe outbreaks of the last
decade, with ca. 240,000 cases reported. We analyzed 21 clinical strains isolated
between 1992 and 2006 from several provinces throughout the country: Benguela,
Bengo, Luanda, Cuando Cubango, and Cabinda. We used two multiplex PCR assays to
investigate discriminatory mobile genetic elements (MGE) [Integrative Conjugative
Elements (ICEs), VSP-II, GI12, GI14, GI15, K, and TLC phages] and we compared the
profiles obtained with those of different reference V. cholerae O1 variants
(prototypical, altered, and hybrid), responsible for the ongoing 7th pandemic. We
also tested the strains for the presence of specific VSP-II variants and for the
presence of a genomic island (GI) (WASA-1), correlated with the transmission of
seventh pandemic cholera from Africa to South America. Based on the
presence/absence of the analyzed genetic elements, five novel profiles were
detected in the epidemic strains circulating in the 1990s. The most frequent
profiles, F and G, were characterized by the absence of ICEs and the three GIs
tested, and the presence of GI WASA-1 and the WASA variant of the VSP-II island.
Our results identified unexpected variability within the 1990s epidemic, showing
different rearrangements in a dynamic part of the genome not present in the
prototypical V. cholerae O1 N16961. Moreover the 2006 strains differed from the
current pandemic V. cholerae O1 strain. Taken together, our results highlight the
role of horizontal gene transfer (HGT) in diversifying the genetic background of
V. cholerae within a single epidemic.
PMID- 24348466
TI - Bespoke microbiome therapy to manage plant diseases.
AB - Information gathered with advanced nucleotide sequencing technologies, small
molecule detection systems and computational biology is revealing that a
community of microbes and their genes, now termed "the microbiome," located in
gut and rhizosphere, is responsible for maintaining the health of human beings
and plants, respectively. Within the complete microbiome a "core-microbiome"
exists that plays the pivotal role in well being of humans and plants. Recent
studies in medicine have shown that an artificial mixture of bacteria
representing the core gut microbiome of healthy person when transferred into gut
of diseased person results in re-establishment of normal microflora in the latter
leading to alleviation from diseased condition. In agriculture, though not
exactly in similar manner as in medicine, success in plant disease management has
been achieved through transfer of microbiome by mixing disease suppressive soils
with disease conducive soils. A study more similar to artificial gut microbiome
transfer in medical field has been recently reported in agriculture, in which
transfer of microbiome via soil solutions (filtered and unfiltered) has shown
ability to alleviate drought stress in Arabidopsis thaliana. However, the exact
practice of transferring artificially cultivated core-microbiome as in medicine
has not thus far been attempted in plant disease management. Nonetheless, as the
gut and rhizosphere microbiome are known to share many common traits, there
exists a good scope for accomplishing similar studies in agriculture. Based upon
the information drawn from all recent works in microbiome studies of gut and
rhizosphere, we propose that tailor-made core-microbiome transfer therapy can be
a success in agriculture too and it could become a viable strategy for management
of plant diseases in future.
PMID- 24348467
TI - Gimme shelter: how Vibrio fischeri successfully navigates an animal's multiple
environments.
AB - Bacteria successfully colonize distinct niches because they can sense and
appropriately respond to a variety of environmental signals. Of particular
interest is how a bacterium negotiates the multiple, complex environments posed
during successful infection of an animal host. One tractable model system to
study how a bacterium manages a host's multiple environments is the symbiotic
relationship between the marine bacterium, Vibrio fischeri, and its squid host,
Euprymna scolopes. V. fischeri encounters many different host surroundings
ranging from initial contact with the squid to ultimate colonization of a
specialized organ known as the light organ. For example, upon recognition of the
squid, V. fischeri forms a biofilm aggregate outside the light organ that is
required for efficient colonization. The bacteria then disperse from this biofilm
to enter the organ, where they are exposed to nitric oxide, a molecule that can
act as both a signal and an antimicrobial. After successfully managing this
potentially hostile environment, V. fischeri cells finally establish their niche
in the deep crypts of the light organ where the bacteria bioluminesce in a
pheromone-dependent fashion, a phenotype that E. scolopes utilizes for anti
predation purposes. The mechanism by which V. fischeri manages these environments
to outcompete all other bacterial species for colonization of E. scolopes is an
important and intriguing question that will permit valuable insights into how a
bacterium successfully associates with a host. This review focuses on specific
molecular pathways that allow V. fischeri to establish this exquisite bacteria
host interaction.
PMID- 24348468
TI - Exploring the risks of phage application in the environment.
AB - Interest in using bacteriophages to control the growth and spread of bacterial
pathogens is being revived in the wake of widespread antibiotic resistance.
However, little is known about the ecological effects that high concentrations of
phages in the environment might have on natural microbial communities. We review
the current evidence suggesting phage-mediated environmental perturbation, with a
focus on agricultural examples, and describe the potential implications for human
health and agriculture. Specifically, we examine the known and potential
consequences of phage application in certain agricultural practices, discuss the
risks of evolved bacterial resistance to phages, and question whether the future
of phage therapy will emulate that of antibiotic treatment in terms of widespread
resistance. Finally, we propose some basic precautions that could preclude such
phenomena and highlight existing methods for tracking bacterial resistance to
phage therapeutic agents.
PMID- 24348469
TI - Methanogens at the top of the world: occurrence and potential activity of
methanogens in newly deglaciated soils in high-altitude cold deserts in the
Western Himalayas.
AB - Methanogens typically occur in reduced anoxic environments. However, in recent
studies it has been shown that many aerated upland soils, including desert soils
also host active methanogens. Here we show that soil samples from high-altitude
cold deserts in the western Himalayas (Ladakh, India) produce CH4 after
incubation as slurry under anoxic conditions at rates comparable to those of hot
desert soils. Samples of matured soil from three different vegetation belts
(arid, steppe, and subnival) were compared with younger soils originating from
frontal and lateral moraines of receding glaciers. While methanogenic rates were
higher in the samples from matured soils, CH4 was also produced in the samples
from the recently deglaciated moraines. In both young and matured soils, those
covered by a biological soil crust (biocrust) were more active than their bare
counterparts. Isotopic analysis showed that in both cases CH4 was initially
produced from H2/CO2 but later mostly from acetate. Analysis of the archaeal
community in the in situ soil samples revealed a clear dominance of sequences
related to Thaumarchaeota, while the methanogenic community comprised only a
minor fraction of the archaeal community. Similar to other aerated soils, the
methanogenic community was comprised almost solely of the genera Methanosarcina
and Methanocella, and possibly also Methanobacterium in some cases. Nevertheless,
~10(3) gdw(-1) soil methanogens were already present in the young moraine soil
together with cyanobacteria. Our results demonstrate that Methanosarcina and
Methanocella not only tolerate atmospheric oxygen but are also able to survive in
these harsh cold environments. Their occurrence in newly deglaciated soils shows
that they are early colonizers of desert soils, similar to cyanobacteria, and may
play a role in the development of desert biocrusts.
PMID- 24348470
TI - Biological CO2 conversion to acetate in subsurface coal-sand formation using a
high-pressure reactor system.
AB - Geological CO2 sequestration in unmineable subsurface oil/gas fields and coal
formations has been proposed as a means of reducing anthropogenic greenhouse
gasses in the atmosphere. However, the feasibility of injecting CO2 into
subsurface depends upon a variety of geological and economic conditions, and the
ecological consequences are largely unpredictable. In this study, we developed a
new flow-through-type reactor system to examine potential geophysical,
geochemical and microbiological impacts associated with CO2 injection by
simulating in-situ pressure (0-100 MPa) and temperature (0-70 degrees C)
conditions. Using the reactor system, anaerobic artificial fluid and CO2 (flow
rate: 0.002 and 0.00001 ml/min, respectively) were continuously supplemented into
a column comprised of bituminous coal and sand under a pore pressure of 40 MPa
(confined pressure: 41 MPa) at 40 degrees C for 56 days. 16S rRNA gene analysis
of the bacterial components showed distinct spatial separation of the predominant
taxa in the coal and sand over the course of the experiment. Cultivation
experiments using sub-sampled fluids revealed that some microbes survived, or
were metabolically active, under CO2-rich conditions. However, no methanogens
were activated during the experiment, even though hydrogenotrophic and
methylotrophic methanogens were obtained from conventional batch-type cultivation
at 20 degrees C. During the reactor experiment, the acetate and methanol
concentration in the fluids increased while the delta(13)Cacetate, H2 and CO2
concentrations decreased, indicating the occurrence of homo-acetogenesis. 16S
rRNA genes of homo-acetogenic spore-forming bacteria related to the genus
Sporomusa were consistently detected from the sandstone after the reactor
experiment. Our results suggest that the injection of CO2 into a natural coal
sand formation preferentially stimulates homo-acetogenesis rather than
methanogenesis, and that this process is accompanied by biogenic CO2 conversion
to acetate.
PMID- 24348471
TI - Desulfotomaculum spp. and related gram-positive sulfate-reducing bacteria in deep
subsurface environments.
AB - Gram-positive spore-forming sulfate reducers and particularly members of the
genus Desulfotomaculum are commonly found in the subsurface biosphere by culture
based and molecular approaches. Due to their metabolic versatility and their
ability to persist as endospores. Desulfotomaculum spp. are well-adapted for
colonizing environments through a slow sedimentation process. Because of their
ability to grow autotrophically (H2/CO2) and produce sulfide or acetate, these
microorganisms may play key roles in deep lithoautotrophic microbial communities.
Available data about Desulfotomaculum spp. and related species from studies
carried out from deep freshwater lakes, marine sediments, oligotrophic and
organic rich deep geological settings are discussed in this review.
PMID- 24348472
TI - Quantification of lincomycin resistance genes associated with lincomycin residues
in waters and soils adjacent to representative swine farms in China.
AB - Lincomycin is commonly used on swine farms for growth promotion as well as
disease treatment and control. Consequently, lincomycin may accumulate in the
environment adjacent to the swine farms in many ways, thereby influencing
antibiotic resistance in the environment. Levels of lincomycin-resistance genes
and lincomycin residues in water and soil samples collected from multiple sites
near wastewater discharge areas were investigated in this study. Sixteen
lincomycin-resistance and 16S rRNA genes were detected using real-time PCR. Three
genes, lnu(F), erm(A), and erm(B), were detected in all water and soil samples
except control samples. Lincomycin residues were determined by rapid resolution
liquid chromatography-tandem mass spectrometry, with concentrations detected as
high as 9.29 ng/mL in water and 0.97 ng/g in soil. A gradual reduction in the
levels of lincomycin-resistance genes and lincomycin residues in the waters and
soils were detected from multiple sites along the path of wastewater discharging
to the surrounding environment from the swine farms. Significant correlations
were found between levels of lincomycin-resistance genes in paired water and soil
samples (r = 0.885, p = 0.019), and between lincomycin-resistance genes and
lincomycin residues (r = 0.975, p < 0.01). This study emphasized the potential
risk of dissemination of lincomycin-resistance genes such as lnu(F), erm(A), and
erm(B), associated with lincomycin residues in surrounding environments adjacent
to swine farms.
PMID- 24348473
TI - Therapeutic use of dendritic cells to promote the extranodal priming of anti
tumor immunity.
AB - Ectopic lymphoid tissue, also known as tertiary lymphoid organs (TLO) develop
adaptively within sites of chronic tissue inflammation, thereby allowing the host
to efficiently crossprime specific immune effector cells within sites of disease.
Recent evidence suggests that the presence of TLO in the tumor microenvironment
(TME) predicts better overall survival. We will discuss the relevance of
extranodal T cell priming within the TME as a means to effectively promote anti
tumor immunity and the strategic use of dendritic cell (DC)-based therapies to
reinforce this clinically preferred process in the cancer-bearing host.
PMID- 24348475
TI - Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from
the Finlay Adjuvant Platform.
AB - The development of effective vaccines against neglected diseases, especially
those associated with poverty and social deprivation, is urgently needed. Modern
vaccine technologies and a better understanding of the immune response have
provided scientists with the tools for rational and safer design of subunit
vaccines. Often, however, subunit vaccines do not elicit strong immune responses,
highlighting the need to incorporate better adjuvants; this step therefore
becomes a key factor for vaccine development. In this review we outline some key
features of modern vaccinology that are linked with the development of better
adjuvants. In line with the increased desire to obtain novel adjuvants for future
vaccines, the Finlay Adjuvant Platform offers a novel approach for the
development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL
(proteoliposome), and AFCo (cochleate), were initially designed for parenteral
and mucosal applications, and constitute potent adjuvants for the induction of
Th1 responses against several antigens. This review summarizes the status of the
Finlay technology in producing promising adjuvants for unsolved-vaccine diseases
including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant
classification, adjuvant selection, and their possible influence on innate
recognition via multiple toll-like receptors are also discussed.
PMID- 24348476
TI - NKT cells as an ideal anti-tumor immunotherapeutic.
AB - Human natural killer T (NKT) cells are characterized by their expression of an
invariant T cell antigen receptor alpha chain variable region encoded by a
Valpha24Jalpha18 rearrangement. These NKT cells recognize alpha
galactosylceramide (alpha-GalCer) in conjunction with the MHC class I-like CD1d
molecule and bridge the innate and acquired immune systems to mediate efficient
and augmented immune responses. A prime example of one such function is adjuvant
activity: NKT cells augment anti-tumor responses because they can rapidly produce
large amounts of IFN-gamma, which acts on NK cells to eliminate MHC negative
tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon
administration of alpha-GalCer-pulsed DCs, both MHC negative and positive tumor
cells can be effectively eliminated, resulting in complete tumor eradication
without tumor recurrence. Clinical trials have been completed in a cohort of 17
patients with advanced non-small cell lung cancers and 10 cases of head and neck
tumors. Sixty percent of advanced lung cancer patients with high IFN-gamma
production had significantly prolonged median survival times of 29.3 months with
only the primary treatment. In the case of head and neck tumors, 10 patients who
completed the trial all had stable disease or partial responses 5 weeks after the
combination therapy of alpha-GalCer-DCs and activated NKT cells. We now focus on
two potential powerful treatment options for the future. One is to establish
artificial adjuvant vector cells containing tumor mRNA and alpha-GalCer/CD1d.
This stimulates host NKT cells followed by DC maturation and NK cell activation
but also induces tumor-specific long-term memory CD8 killer T cell responses,
suppressing tumor metastasis even 1 year after the initial single injection. The
other approach is to establish induced pluripotent stem (iPS) cells that can
generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived
NKT cells produce IFN-gamma in vitro and in vivo upon stimulation with alpha
GalCer/DCs, and mediated adjuvant effects, suppressing tumor growth in vivo.
PMID- 24348477
TI - Inhibitory receptor signaling destabilizes immunological synapse formation in
primary NK cells.
AB - Upon engagement of their cognate class I major histocompatibility complex
ligands, receptors containing immunotyrosine-based inhibitory motifs (ITIMs)
transduce signals that block cytolytic and inflammatory responses. In this
manner, ITIM-coupled receptors play a crucial role in maintaining natural killer
(NK) cell tolerance toward normal, healthy tissue. A number of studies, mostly
using immortalized NK cell lines, have demonstrated that ITIM signaling functions
by disrupting the cytolytic immunological synapse formed between an NK cell and
its target. However, more recent imaging experiments using primary NK cells have
suggested that inhibitory receptor engagement does not antagonize contact
formation, casting doubt on the hypothesis that ITIM signals destabilize the
synapse. To resolve this issue, we analyzed primary NK cell activation and
contact formation on supported lipid bilayers containing controlled combinations
of activating and inhibitory ligands. Under these conditions, we observed that
ITIM signaling clearly inhibited adhesion, cell arrest, and calcium influx, three
hallmarks of synapse formation. These results are consistent with previous
reports showing that inhibitory receptors deliver a "reverse stop" signal, and
confirm that ITIM signaling functions at least in part by destabilizing cytolytic
synapse formation.
PMID- 24348474
TI - The gastrointestinal frontier: IgA and viruses.
AB - Viral gastroenteritis is one of the leading causes of diseases that kill ~2.2
million people worldwide each year. IgA is one of the major immune effector
products present in the gastrointestinal tract yet its importance in protection
against gastrointestinal viral infections has been difficult to prove. In part
this has been due to a lack of small and large animal models in which
pathogenesis of and immunity to gastrointestinal viral infections is similar to
that in humans. Much of what we have learned about the role of IgA in the
intestinal immune response has been obtained from experimental animal models of
rotavirus infection. Rotavirus-specific intestinal IgA appears to be one of the
principle effectors of long term protection against rotavirus infection. Thus,
there has been a focus on understanding the immunological pathways through which
this virus-specific IgA is induced during infection. In addition, the
experimental animal models of rotavirus infection provide excellent systems in
which new areas of research on viral-specific intestinal IgA including the long
term maintenance of viral-specific IgA.
PMID- 24348478
TI - In the crosshairs: investigating lytic granules by high-resolution microscopy and
electrophysiology.
AB - Cytotoxic T lymphocytes (CTLs) form an integral part of the adaptive immune
system. Their main function is to eliminate bacteria- and virus-infected target
cells by releasing perforin and granzymes (the lethal hit) contained within lytic
granules (LGs), at the CTL-target-cell interface [the immunological synapse
(IS)]. The formation of the IS as well as the final events at the IS leading to
target-cell death are both highly complex and dynamic processes. In this review
we highlight and discuss three high-resolution techniques that have proven
invaluable in the effort to decipher key features of the mechanism of CTL
effector function and in particular lytic granule maturation and fusion.
Correlative light and electron microscopy allows the correlation between
organelle morphology and localization of particular proteins, while total
internal reflection fluorescence microscopy (TIRFM) enables the study of lytic
granule dynamics at the IS in real time. The combination of TIRFM with patch
clamp membrane capacitance measurements finally provides a tool to quantify the
size of fusing LGs at the IS.
PMID- 24348481
TI - Clinical Implications of Co-Inhibitory Molecule Expression in the Tumor
Microenvironment for DC Vaccination: A Game of Stop and Go.
AB - The aim of therapeutic dendritic cell (DC) vaccines in cancer immunotherapy is to
activate cytotoxic T cells to recognize and attack the tumor. T cell activation
requires the interaction of the T cell receptor with a cognate major
histocompatibility complex-peptide complex. Although initiated by antigen
engagement, it is the complex balance between co-stimulatory and co-inhibitory
signals on DCs that results in T cell activation or tolerance. Even when already
activated, tumor-specific T cells can be neutralized by the expression of co
inhibitory molecules on tumor cells. These and other immunosuppressive cues in
the tumor microenvironment are major factors currently hampering the application
of DC vaccination. In this review, we discuss recent data regarding the essential
and complex role of co-inhibitory molecules in regulating the immune response
within the tumor microenvironment. In particular, possible therapeutic
intervention strategies aimed at reversing or neutralizing suppressive networks
within the tumor microenvironment will be emphasized. Importantly, blocking co
inhibitory molecule signaling, often referred to as immune checkpoint blockade,
does not necessarily lead to an effective activation of tumor-specific T cells.
Therefore, combination of checkpoint blockade with other immune potentiating
therapeutic strategies, such as DC vaccination, might serve as a synergistic
combination, capable of reversing effector T cells immunosuppression while at the
same time increasing the efficacy of T cell-mediated immunotherapies. This will
ultimately result in long-term anti-tumor immunity.
PMID- 24348479
TI - The past, present, and future of immune repertoire biology - the rise of next
generation repertoire analysis.
AB - T and B cell repertoires are collections of lymphocytes, each characterized by
its antigen-specific receptor. We review here classical technologies and analysis
strategies developed to assess immunoglobulin (IG) and T cell receptor (TR)
repertoire diversity, and describe recent advances in the field. First, we
describe the broad range of available methodological tools developed in the past
decades, each of which answering different questions and showing complementarity
for progressive identification of the level of repertoire alterations: global
overview of the diversity by flow cytometry, IG repertoire descriptions at the
protein level for the identification of IG reactivities, IG/TR CDR3 spectratyping
strategies, and related molecular quantification or dynamics of T/B cell
differentiation. Additionally, we introduce the recent technological advances in
molecular biology tools allowing deeper analysis of IG/TR diversity by next
generation sequencing (NGS), offering systematic and comprehensive sequencing of
IG/TR transcripts in a short amount of time. NGS provides several angles of
analysis such as clonotype frequency, CDR3 diversity, CDR3 sequence analysis, V
allele identification with a quantitative dimension, therefore requiring high
throughput analysis tools development. In this line, we discuss the recent
efforts made for nomenclature standardization and ontology development. We then
present the variety of available statistical analysis and modeling approaches
developed with regards to the various levels of diversity analysis, and reveal
the increasing sophistication of those modeling approaches. To conclude, we
provide some examples of recent mathematical modeling strategies and perspectives
that illustrate the active rise of a "next-generation" of repertoire analysis.
PMID- 24348483
TI - MicroRNAs: The Missing Link in the Biology of Graft-Versus-Host Disease?
AB - Graft-versus-host disease (GVHD) is still the major complication of allogeneic
hematopoietic stem cell transplantation. Despite extensive studies in
understanding the pathophysiology of GVHD, its pathogenesis remains unclear.
Recently, important functions of microRNAs have been demonstrated in various
autoimmune diseases and cancers such as psoriasis and lymphoma. This review
highlights the need to investigate the role of microRNAs in GVHD and hypothesizes
that microRNAs may be one of the missing links in our understanding of GVHD, with
the potential for novel therapeutics.
PMID- 24348482
TI - The dark side of dendritic cells: development and exploitation of tolerogenic
activity that favor tumor outgrowth and immune escape.
AB - Dendritic cells (DC) play a central role in the regulation of the immune
responses by providing the information needed to decide between tolerance,
ignorance, or active responses. For this reason different therapies aim at
manipulating DC to obtain the desired response, such as enhanced cell-mediated
toxicity against tumor and infected cells or the induction of tolerance in
autoimmunity and transplantation. In the last decade studies performed in these
settings have started to identify (some) molecules/factors involved in the
acquisition of a tolerogenic DC phenotype as well as the underlying mechanisms of
their regulatory function on different immune cell populations.
PMID- 24348484
TI - The importance of aboveground-belowground interactions on the evolution and
maintenance of variation in plant defense traits.
AB - Over the past two decades a growing body of empirical research has shown that
many ecological processes are mediated by a complex array of indirect
interactions occurring between rhizosphere-inhabiting organisms and those found
on aboveground plant parts. Aboveground-belowground studies have thus far focused
on elucidating processes and underlying mechanisms that mediate the behavior and
performance of invertebrates in opposite ecosystem compartments. Less is known
about genetic variation in plant traits such as defense as that may be driven by
above- and belowground trophic interactions. For instance, although our
understanding of genetic variation in aboveground plant traits and its effects on
community-level interactions is well developed, little is known about the
importance of aboveground-belowground interactions in driving this variation.
Plant traits may have evolved in response to selection pressures from above- and
below-ground interactions from antagonists and mutualists. Here, we discuss gaps
in our understanding of genetic variation in plant-related traits as they relate
to aboveground and belowground multitrophic interactions. When metabolic
resources are limiting, multiple attacks by antagonists in both domains may lead
to trade-offs. In nature, these trade-offs may critically depend upon their
effects on plant fitness. Natural enemies of herbivores may also influence
selection for different traits via top-down control. At larger scales these
interactions may generate evolutionary "hotspots" where the expression of various
plant traits is the result of strong reciprocal selection via direct and indirect
interactions. The role of abiotic factors in driving genetic variation in plant
traits is also discussed.
PMID- 24348486
TI - Operation of trans-thylakoid thiol-metabolizing pathways in photosynthesis.
AB - Thiol oxidation to disulfides and the reverse reaction, i.e., disulfide reduction
to free thiols, are under the control of catalysts in vivo. Enzymatically
assisted thiol-disulfide chemistry is required for the biogenesis of all energy
transducing membrane systems. However, until recently, this had only been
demonstrated for the bacterial plasma membrane. Long considered to be vacant, the
thylakoid lumen has now moved to the forefront of photosynthesis research with
the realization that its proteome is far more complicated than initially
anticipated. Several lumenal proteins are known to be disulfide bonded in
Arabidopsis, highlighting the importance of sulfhydryl oxidation in the thylakoid
lumen. While disulfide reduction in the plastid stroma is known to activate
several enzymatic activities, it appears that it is the reverse reaction, i.e.,
thiol oxidation that is required for the activity of several lumen-resident
proteins. This paradigm for redox regulation in the thylakoid lumen has opened a
new frontier for research in the field of photosynthesis. Of particular
significance in this context is the discovery of trans-thylakoid redox pathways
controlling disulfide bond formation and reduction, which are required for
photosynthesis.
PMID- 24348485
TI - Dissecting the integrative antioxidant and redox systems in plant mitochondria.
Effect of stress and S-nitrosylation.
AB - Mitochondrial respiration provides the energy needed to drive metabolic and
transport processes in cells. Mitochondria are a significant site of reactive
oxygen species (ROS) production in plant cells, and redox-system components obey
fine regulation mechanisms that are essential in protecting the mitochondrial
integrity. In addition to ROS, there are compelling indications that nitric oxide
can be generated in this organelle by both reductive and oxidative pathways. ROS
and reactive nitrogen species play a key role in signaling but they can also be
deleterious via oxidation of macromolecules. The high production of ROS obligates
mitochondria to be provided with a set of ROS scavenging mechanisms. The first
line of mitochondrial antioxidants is composed of superoxide dismutase and the
enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge
ROS but also to repair cell damage and possibly serve as redox sensors. The
dithiol-disulfide exchanges form independent signaling nodes and act as
antioxidant defense mechanisms as well as sensor proteins modulating redox
signaling during development and stress adaptation. The presence of thioredoxin
(Trx), peroxiredoxin (Prx) and sulfiredoxin (Srx) in the mitochondria has been
recently reported. Cumulative results obtained from studies in salt stress models
have demonstrated that these redox proteins play a significant role in the
establishment of salt tolerance. The Trx/Prx/Srx system may be subjected to a
fine regulated mechanism involving post-translational modifications, among which
S-glutathionylation and S-nitrosylation seem to exhibit a critical role that is
just beginning to be understood. This review summarizes our current knowledge in
antioxidative systems in plant mitochondria, their interrelationships, mechanisms
of compensation and some unresolved questions, with special focus on their
response to abiotic stress.
PMID- 24348488
TI - Desiccation tolerance in resurrection plants: new insights from transcriptome,
proteome and metabolome analysis.
AB - Most higher plants are unable to survive desiccation to an air-dried state. An
exception is a small group of vascular angiosperm plants, termed resurrection
plants. They have evolved unique mechanisms of desiccation tolerance and thus can
tolerate severe water loss, and mostly adjust their water content with the
relative humidity in the environment. Desiccation tolerance is a complex
phenomenon and depends on the regulated expression of numerous genes during
dehydration and subsequent rehydration. Most of the resurrection plants have a
large genome and are difficult to transform which makes them unsuitable for
genetic approaches. However, technical advances have made it possible to analyze
changes in gene expression on a large-scale. These approaches together with
comparative studies with non-desiccation tolerant plants provide novel insights
into the molecular processes required for desiccation tolerance and will shed
light on identification of orphan genes with unknown functions. Here, we review
large-scale recent transcriptomic, proteomic, and metabolomic studies that have
been performed in desiccation tolerant plants and discuss how these studies
contribute to understanding the molecular basis of desiccation tolerance.
PMID- 24348487
TI - The GIP gamma-tubulin complex-associated proteins are involved in nuclear
architecture in Arabidopsis thaliana.
AB - During interphase, the microtubular cytoskeleton of cycling plant cells is
organized in both cortical and perinuclear arrays. Perinuclear microtubules (MTs)
are nucleated from gamma-Tubulin Complexes (gamma-TuCs) located at the surface of
the nucleus. The molecular mechanisms of gamma-TuC association to the nuclear
envelope (NE) are currently unknown. The gamma-TuC Protein 3 (GCP3)-Interacting
Protein 1 (GIP1) is the smallest gamma-TuC component identified so far. AtGIP1
and its homologous protein AtGIP2 participate in the localization of active gamma
TuCs at interphasic and mitotic MT nucleation sites. Arabidopsis gip1gip2 mutants
are impaired in establishing a fully functional mitotic spindle and exhibit
severe developmental defects. In this study, gip1gip2 knock down mutants were
further characterized at the cellular level. In addition to defects in both the
localization of gamma-TuC core proteins and MT fiber robustness, gip1gip2 mutants
exhibited a severe alteration of the nuclear shape associated with an abnormal
distribution of the nuclear pore complexes. Simultaneously, they showed a
misorganization of the inner nuclear membrane protein AtSUN1. Furthermore, AtGIP1
was identified as an interacting partner of AtTSA1 which was detected, like the
AtGIP proteins, at the NE. These results provide the first evidence for the
involvement of a gamma-TuC component in both nuclear shaping and NE organization.
Functional hypotheses are discussed in order to propose a model for a GIP
dependent nucleo-cytoplasmic continuum.
PMID- 24348489
TI - Buffering growth variations against water deficits through timely carbon usage.
AB - Water stresses reduce plant growth but there is no consensus on whether carbon
metabolism has any role in this reduction. Sugar starvation resulting from
stomatal closure is often proposed as a cause of growth impairment under long
term or severe water deficits. However, growth decreases faster than
photosynthesis in response to drought, leading to increased carbohydrate stores
under short-term or moderate water deficits. Here, we addressed the question of
the role of carbon availability on growth under moderate water deficits using two
different systems. Firstly, we monitored the day/night pattern of leaf growth in
Arabidopsis plants. We show that a moderate soil water deficit promotes leaf
growth at night in mutants severely disrupted in their nighttime carbohydrate
availability. This suggests that soil water deficit promotes carbon satiation.
Secondly, we monitored the sub-hourly growth variations of clementine fruits in
response to daily, natural fluctuations in air water deficit, and at contrasting
source-sink balances obtained by defoliation. We show that high carbohydrate
levels prevent excessive, hydraulic shrinkage of the fruit during days with high
evaporative demand, most probably through osmotic adjustment. Together, our
results contribute to the view that growing organs under moderate soil or air
water deficit are not carbon starved, but use soluble carbohydrate in excess to
partly release a hydromechanical limitation of growth.
PMID- 24348490
TI - Contrasting xylem vessel constraints on hydraulic conductivity between native and
non-native woody understory species.
AB - We examined the hydraulic properties of 82 native and non-native woody species
common to forests of Eastern North America, including several congeneric groups,
representing a range of anatomical wood types. We observed smaller conduit
diameters with greater frequency in non-native species, corresponding to lower
calculated potential vulnerability to cavitation index. Non-native species
exhibited higher vessel-grouping in metaxylem compared with native species,
however, solitary vessels were more prevalent in secondary xylem. Higher
frequency of solitary vessels in secondary xylem was related to a lower potential
vulnerability index. We found no relationship between anatomical characteristics
of xylem, origin of species and hydraulic conductivity, indicating that non
native species did not exhibit advantageous hydraulic efficiency over native
species. Our results confer anatomical advantages for non-native species under
the potential for cavitation due to freezing, perhaps permitting extended growing
seasons.
PMID- 24348491
TI - Functional recapitulation of transitions in sexual systems by homeosis during the
evolution of dioecy in Thalictrum.
AB - Sexual systems are highly variable in flowering plants and an important
contributor to floral diversity. The ranunculid genus Thalictrum is especially
well-suited to study evolutionary transitions in sexual systems. Homeotic
transformation of sexual organs (stamens and carpels) is a plausible mechanism
for the transition from hermaphroditic to unisexual flowers in this lineage
because flowers of dioecious species develop unisexually from inception. The
single-copy gene PISTILLATA (PI) constitutes a likely candidate for rapid
switches between stamen and carpel identity. Here, we first characterized the
expression pattern of all B class genes in the dioecious species T. dioicum. As
expected, all B class orthologs are expressed in stamens from the earliest
stages. Certain AP3 lineages were also expressed late in sepal development. We
then tested whether orthologs of PI could potentially control sexual system
transitions in Thalictrum, by knocking-down their expression in T. dioicum and
the hermaphroditic species T. thalictroides. In T. dioicum, we found that ThdPI
1/2 silencing caused stamen primordia to develop into carpels, resulting in male
to female flower conversions. In T. thalictroides, we found that ThtPI silencing
caused stamen primordia to develop into supernumerary carpels, resulting in
hermaphroditic to female flower conversions. These phenotypes illustrate the
ability for homeotic mutations to bring about sudden and potentially adaptive
changes by altering the function of a single gene. We propose a two-step
evolutionary model where transitions from hermaphroditic to unisexual plants in
Thalictrum result from two independent mutations at a B class gene locus. Our PI
knockdown experiments in T. thalictroides recapitulate the second step in this
model: the evolution of female plants as a result of a loss-of-function mutation
in a B class gene.
PMID- 24348492
TI - Comparative profiling of miRNA expression in developing seeds of high linoleic
and high oleic safflower (Carthamus tinctorius L.) plants.
AB - Vegetable oils high in oleic acid are considered to be advantageous because of
their better nutritional value and potential industrial applications. The oleic
acid content in the classic safflower oil is normally 10-15% while a natural
mutant (ol) accumulates elevated oleic acid up to 70% in seed oil. As a part of
our investigation into the molecular features of the high oleic (HO) trait in
safflower we have profiled the microRNA (miRNA) populations in developing
safflower seeds expressing the ol allele in comparison to the wild type high
linoleic (HL) safflower using deep sequencing technology. The small RNA
populations of the mid-maturity developing embryos of homozygous ol HO and wild
type HL safflower had a very similar size distribution pattern, however, only
~16.5% of the unique small RNAs were overlapping in these two genotypes. From
these two small RNA populations we have found 55 known miRNAs and identified two
candidate novel miRNA families to be likely unique to the developing safflower
seeds. Target genes with conserved as well as novel functions were predicted for
the conserved miRNAs. We have also identified 13 miRNAs differentially expressed
between the HO and HL safflower genotypes. The results may lay a foundation for
unraveling the miRNA-mediated molecular processes that regulate oleic acid
accumulation in the HO safflower mutant and developmental processes in safflower
embryos in general.
PMID- 24348493
TI - Cellular iron homeostasis and metabolism in plant.
PMID- 24348494
TI - The impact of high temperatures on Vitis vinifera cv. Semillon grapevine
performance and berry ripening.
AB - The heat event that occurred in many parts of Australia in 2009 was the worst on
record for the past decade, with air temperatures exceeding 40( degrees )C for 14
days. Our aim was to assess the impacts of this heat event on vine performance,
including ripening, yield, and gas exchange of Vitis vinifera cv. Semillon grown
in a Riverina vineyard. To assess the affect of high temperatures on Semillon
grapevines, the vines were covered with a protective layer to reduce radiant
heating and were compared with vines exposed to ambient conditions. The heat
event had major effects on ripening; reducing the rate of ripening by 50% and
delaying harvest ripeness and causing a high incidence of berry shrivel and
sunburn. Yield was not affected. Photosynthesis was reduced 35% by the heat event
while transpiration increased nearly threefold and was accounted for by increased
stomatal conductance. The conclusion of this study was that heat events delayed
ripening in Semillon berries and caused a significant reduction in berry quality.
Strategies to minimize the radiant load during heat events are required and this
study has confirmed a protective layer can reduce canopy temperatures and enhance
berry quality.
PMID- 24348495
TI - Erratum: Iron biofortification and homeostasis in transgenic cassava roots
expressing an algal iron assimilatory protein, FEA1.
AB - [This corrects the article on p. 171 in vol. 3, PMID: 22993514.].
PMID- 24348497
TI - Importance of the hexagonal lipid phase in biological membrane organization.
AB - Domains are present in every natural membrane. They are characterized by a
distinctive protein and/or lipid composition. Their size is highly variable from
the nano- to the micrometer scale. The domains confer specific properties to the
membrane leading to original structure and function. The determinants leading to
domain organization are therefore important but remain obscure. This review
presents how the ability of lipids to organize into hexagonal II or lamellar
phases can promote particular local structures within membranes. Since biological
membranes are composed of a mixture of lipids, each with distinctive biophysical
properties, lateral and transversal sorting of lipids can promote creation of
domains inside the membrane through local modulation of the lipid phase. Lipid
biophysical properties have been characterized for long based on in vitro
analyses using non-natural lipid molecules; their re-examinations using natural
lipids might open interesting perspectives on membrane architecture occurring in
vivo in various cellular and physiological contexts.
PMID- 24348496
TI - Reprogramming cells to study vacuolar development.
AB - During vegetative and embryonic developmental transitions, plant cells are
massively reorganized to support the activities that will take place during the
subsequent developmental phase. Studying cellular and subcellular changes that
occur during these short transitional periods can sometimes present challenges,
especially when dealing with Arabidopsis thaliana embryo and seed tissues. As a
complementary approach, cellular reprogramming can be used as a tool to study
these cellular changes in another, more easily accessible, tissue type. To
reprogram cells, genetic manipulation of particular regulatory factors that play
critical roles in establishing or repressing the seed developmental program can
be used to bring about a change of cell fate. During different developmental
phases, vacuoles assume different functions and morphologies to respond to the
changing needs of the cell. Lytic vacuoles (LVs) and protein storage vacuoles
(PSVs) are the two main vacuole types found in flowering plants such as
Arabidopsis. Although both are morphologically distinct and carry out unique
functions, they also share some similar activities. As the co-existence of the
two vacuole types is short-lived in plant cells, how they replace each other has
been a long-standing curiosity. To study the LV to PSV transition, LEAFY
COTYLEDON2, a key transcriptional regulator of seed development, was
overexpressed in vegetative cells to activate the seed developmental program. At
the cellular level, Arabidopsis leaf LVs were observed to convert to PSV-like
organelles. This presents the opportunity for further research to elucidate the
mechanism of LV to PSV transitions. Overall, this example demonstrates the
potential usefulness of cellular reprogramming as a method to study cellular
processes that occur during developmental transitions.
PMID- 24348498
TI - Stroke types in rural and urban northern portugal: incidence and 7-year survival
in a community-based study.
AB - BACKGROUND/AIM: Differences in stroke incidence and mortality between regions
could stem from differences in the incidence of particular stroke types and long
term prognosis. The aim of this study was to investigate whether different risk
profiles and stroke types underlie the difference in stroke incidence and patient
long-term survival in rural and urban populations. METHODS: All suspected first
ever-in-a-lifetime strokes occurring between October 1998 and September 2000 in
37,290 residents of rural municipalities and in 86,023 individuals living in the
city of Porto were entered into a population-based registry. Standard definitions
of stroke types and overlapping comprehensive sources of information were used
for patient identification. Patients were examined by neurologists at 3 months, 1
year and 7 years after the index event. RESULTS: From a total of 688 patients
included (226 in rural and 462 in urban areas), 76.2% had an ischaemic stroke
(IS; 75.3 vs. 77.9%), 16.1% a primary intracerebral haemorrhage (PICH; 16.3 vs.
14.6%) and 3.3% a subarachnoid haemorrhage (SAH; 2.7 vs. 3.7%); in 4.4% (4.9 vs.
4.1%), the stroke type could not be determined. The annual incidence rate per
1,000 was 2.13 (95% CI, 1.95-2.31), 0.45 (95% CI, 0.37-0.53), 0.09 (95% CI, 0.06
0.14) and 0.12 (95% CI, 0.08-0.17), respectively. The age-specific rural/urban
incidence rate ratios for IS in the youngest group (<55 years) was 0.27 (95% CI,
0.11-0.69), increasing to 1.47 (95% CI, 1.07-2.01) for those aged 65-74 years and
to 1.87 (95% CI, 1.39-2.52) for those between 75 and 84 years. Rural compared to
urban patients with an IS were predominantly men, had a prevalence ratio (PR) of
1.28 (95% CI, 1.05-1.56), were 65 years or older (PR = 1.18; 95% CI, 1.08-1.30)
and had in general a lower prevalence of risk factors. There was no evidence of
rural/urban differences in 28-day case fatality for the stroke types, although IS
tended to be less fatal among urban patients (10.3 vs. 13.1%), whereas PICH (33.3
vs. 24.2%) and SAH (35.3 vs. 16.7%) were less fatal among rural patients.
Independently of rural/urban residence, predictors of poor survival after the
acute phase (28 days) were age >65 years (HR = 3.57; 95% CI, 2.6-4.9), diabetes
(HR = 1.5; 95% CI, 1.2-1.9), ischaemic heart disease (HR = 1.8; 95% CI, 1.3-2.6),
atrial fibrillation (HR = 1.5; 95% CI, 1.1-2.0) and smoking habits (HR = 1.6; 95%
CI, 1.1-2.3). CONCLUSIONS: The age pattern of IS incidence marks the difference
between rural and urban populations; the youngest urban and the oldest rural
residents were at a higher risk. Although patients from rural areas were older,
the relatively lower prevalence of simultaneously occurring risk and prognostic
factors among them as well as the similar management of rural and urban patients
may justify why rurality is not associated with long-term survival.
PMID- 24348499
TI - Intravenous thrombolysis in a stroke patient receiving rivaroxaban.
PMID- 24348500
TI - The effect of psychosocial support intervention on depression in patients with
dementia and their family caregivers: an assessor-blinded randomized controlled
trial.
AB - BACKGROUND/AIM: A three-component tailored psychosocial 12-month assessor-blinded
randomized controlled trial to reduce depression in people with dementia (PWD)
and carers was conducted. METHODS: A total of 230 home-dwelling dyads of PWD and
their carers were randomized to usual care or intervention consisting of three
components over 12 months. Primary outcomes were the difference between the
baseline and 12-month score on the Cornell Scale of Depression in Dementia (CSDD)
in the PWD and on the Geriatric Depression Scale (GDS) in the carers. RESULTS:
The intent-to-treat difference between the baseline and 12-month change score was
not significant between the intervention and control groups for the CSDD (p =
0.95) or GDS (p = 0.82). CONCLUSIONS: The trial did not show a significant
difference between usual care and the intervention on depressive symptoms in PWD
or their family caregivers. (c) 2013 S. Karger AG, Basel.
PMID- 24348501
TI - Cognitive activities and instrumental activity of daily living in older adults
with mild cognitive impairment.
AB - AIMS: This study aimed to identify differences in the implementation of cognitive
activities and instrumental activities of daily living (IADLs) between healthy
individuals and subjects with mild cognitive impairment (MCI). METHODS: The study
included 2,498 cognitively healthy subjects (mean age, 71.2 +/- 5.1 years) and
809 MCI subjects (mean age, 71.8 +/- 5.4 years). The subjects were interviewed
regarding their participation in cognitive activities and the implementation of
IADLs. RESULTS: We found a significant association between participation in any
cognitive activities (p < 0.001), using a bus or a train (p < 0.001), and MCI.
After adjusting for covariates, cognitive activity of any type remained
significantly associated with MCI (p < 0.005) but not with the implementation of
IADLs. CONCLUSIONS: Our study revealed that greater participation in cognitive
activity was associated with lower odds of MCI. Participation in cognitive
activities may reflect differences between healthy and MCI subjects. To clarify
the causal relationship between cognitive activities and MCI, further studies are
required.
PMID- 24348502
TI - Reliability and Validity of the Clinical Dementia Rating for Community-Living
Elderly Subjects without an Informant.
AB - BACKGROUND: The Clinical Dementia Rating (CDR) scale is widely used to assess
cognitive impairment in Alzheimer's disease. It requires collateral information
from a reliable informant who is not available in many instances. We adapted the
original CDR scale for use with elderly subjects without an informant (CDR-NI)
and evaluated its reliability and validity for assessing mild cognitive
impairment (MCI) and dementia among community-dwelling elderly subjects. METHOD:
At two consecutive visits 1 week apart, nurses trained in CDR assessment
interviewed, observed and rated cognitive and functional performance according to
a protocol in 90 elderly subjects with suboptimal cognitive performance [Mini
Mental State Examination (MMSE) <26 and/or Montreal Cognitive Assessment (MOCA)
<26] and without informants according to a protocol. CDR domains and global
scores were assigned after the second visit based upon corroborative information
from the subjects' responses to questions, role-play, and observed performance in
specifically assigned tasks at home and within the community. RESULTS: The CDR-NI
scores (0, 0.5, 1) showed good internal consistency (Crohnbach's alpha 0.83
0.84), inter-rater reliability (kappa 0.77-1.00 for six domains and 0.95 for
global rating) and test-retest reliability (kappa 0.75-1.00 for six domains and
0.80 for global rating), good agreement (kappa 0.79) with the clinical assessment
status of MCI (n = 37) and dementia (n = 4) and significant differences in the
mean scores for MMSE, MOCA and Instrumental Activities of Daily Living (ANOVA
global p < 0.001). CONCLUSION: Owing to the protocol of the interviews,
assessments and structured observations gathered during the two visits, CDR-NI
provides valid and reliable assessment of MCI and dementia in community-living
elderly subjects without an informant.
PMID- 24348503
TI - Optimization of the inclusion of Alzheimer's disease patients in international
multicenter randomized trials: results of a national survey conducted in memory
research centers in france.
AB - INTRODUCTION: Since 2002, with the creation of Centers of Memory Resources and
Research (CMRR), considerable progress has been made in France regarding the
administrative and institutional framework within which Alzheimer's disease (AD)
is managed. In this study, we explore three approaches that can help optimize the
inclusion of patients in clinical trials related to AD. They are as follows: to
assess communication concerning clinical trials on AD in French CMRR, to analyze
the internal organization of these centers concerning the dynamics of inclusion,
and to evaluate screening tools used. METHODS: A national, descriptive, cross
sectional survey was conducted in all CMRR in France between May 1 and July 31,
2011, using a self-administered questionnaire. All investigators,
subinvestigators and the relevant CMRR personnel were involved. RESULTS: A total
of 75% of the CMRR participated, and about 30% of the physicians contacted
responded positively to the survey. Only 50% reported having communicated with
health care professionals at least once in the previous 3 months, and less than
50% had communicated occasionally with the general public. A total of 75% of
those surveyed had a research group but only half of the groups were active, 50%
of the physicians did not have a consultation time dedicated to study
recruitment, and 75% of the respondents had a screening tool in their CMRR but
over half of them were not satisfied with it. CONCLUSION: This investigation
provides a basis for improving the screening of patients by both internal
organizational development and adaptation of tools already available. Improvement
requires promoting regular communication that is appropriate and targeted to
health care professionals, smaller memory centers, associations and the public,
and therefore, familiarizing the whole population with clinical research on AD.
PMID- 24348505
TI - Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Acute Kidney Injury
in Patients with Morbid Obesity Who Underwent Bariatric Surgery.
AB - INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) has been
identified as a biomarker of acute kidney injury (AKI) that could contribute to
early diagnosis and effective management of AKI. The purpose of this study was to
evaluate NGAL as a predictive marker of AKI in patients with clinically severe
obesity (BMI >50) who underwent biliopancreatic diversion surgery. PATIENTS AND
METHODS: We prospectively studied 23 patients with clinically severe obesity who
underwent biliopancreatic bypass surgery. NGAL was measured using
chemiluminescent microparticle immunoassay in three urine samples collected from
each patient before surgery (first sample), 2-6 h after surgery (second sample)
and on the first postoperative day (third sample). RESULTS: Renal function was
evaluated using serum creatinine values, which were 0.91 +/- 0.26 mg/dl before
surgery, 0.87 +/- 0.31 mg/dl immediately after surgery and 0.92 +/- 0.62 mg/dl on
the fifth postoperative day. During the immediate postoperative period, AKI was
observed in 2 patients, one of whom required renal replacement therapy with
hemodialysis. In both patients, urine NGAL increased within the first
postoperative hours before the values of serum creatinine increased. CONCLUSION:
Urine NGAL in patients with clinically severe obesity, which was surgically
treated, might be a potential biomarker of early AKI detection. Further research
is required in order to confirm these results observed in a small number of
patients who developed postoperative AKI and make recommendations for predictive
NGAL values in patients who underwent bariatric surgery.
PMID- 24348504
TI - Predictors of institutionalization of dementia patients in mild and moderate
stages: a 4-year prospective analysis.
AB - BACKGROUND: Institutionalization is the most important milestone in the care of
dementia patients. This study was aimed at identifying relevant predictors of
institutionalization in a broad empirical context and interpreting them on the
basis of the predictor model proposed by Luppa et al. [Dement Geriatr Cogn Disord
2008;26:65-78]. METHODS: At the start of this study, 357 patients with mild to
moderate dementia were examined by their general practitioners, and a telephone
interview was conducted with their caregivers. Four years later, the outcomes
'institutionalization' and 'death' were determined from health insurance data.
Forty-one variables were examined for their predictive influence by univariate
and multivariate Cox regression. RESULTS: The risk of institutionalization
increased significantly (p <= 0.05) with older ages of patients [hazard ratio
(HR) = 1.05] and caregivers (HR = 1.03), a higher educational level of the
caregiver (HR = 1.83), greater use of community health services (HR = 1.59),
greater caregiver burden (HR = 1.02), and when the caregiver and patient lived
apart (HR = 1.97). CONCLUSION: The results show that there is a multifactorial
influence on institutionalization of dementia patients by sociodemographic,
health-related, and psychological aspects as well as the care situation, thus
validating the predictor model by Luppa et al. [Dement Geriatr Cogn Disord
2008;26:65-78]. Caregiver burden was found to be the strongest predictor
accessible to interventions.
PMID- 24348506
TI - The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is
Mitigated by Inflammation Markers.
AB - BACKGROUND: Fibroblast growth factor-23 (FGF-23) has been linked to vascular
calcification, ventricular hypertrophy and mortality in chronic kidney disease
(CKD), although these links may not be direct and independent. Similar grave
outcomes are associated with inflammation and oxidative stress in CKD. Recently,
accumulating evidence has linked components of phosphate homeostasis to
inflammation and oxidative stress. The interaction between the triad of
inflammation, FGF-23 and cardiovascular outcomes is underinvestigated. METHODS:
We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23,
high-sensitivity C-reactive protein (hsCRP), endogenous soluble receptor of
advanced glycation end products (esRAGE), advanced oxidation protein products
(AOPP), parathormone, lipids, calcium and phosphorous were measured. The aortic
calcification index (ACI) was determined using non-contrast CT scans of the
abdominal aorta. RESULTS: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906) and
correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in
univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus
but not esRAGE were all significantly correlated to FGF-23 (R2 = 0.7, p < 0.001).
In univariate analysis, ACI correlated with hsCRP, esRAGE, FGF-23, dialysis
vintage, systolic blood pressure (BP) and serum cholesterol. In multiple
regression analysis not including inflammation markers, ACI was associated with
FGF-23. However, inclusion of inflammation markers in another multiple regression
analyses showed that ACI correlated with hsCRP, BP, dialysis vintage and esRAGE
but not with FGF-23 (R2 = 0.65, p < 0.001). CONCLUSION: FGF-23 is strongly
correlated to various markers of inflammation and oxidative stress in
hemodialysis patients. The association between FGF-23 and vascular calcification
was mitigated when corrected for inflammation markers.
PMID- 24348507
TI - Adjusted Anion Gap Is Associated with Glomerular Filtration Rate Decline in
Chronic Kidney Disease.
AB - BACKGROUND: Metabolic acidosis is known to accelerate the progression of chronic
kidney disease (CKD). However, whether undetermined anions as indicated by the
adjusted anion gap (aAG) are associated with estimated glomerular filtration rate
(eGFR) decline in patients with CKD is unclear. METHODS: Data from 42 patients
with CKD (baseline eGFR, 7.1-52.0 ml/min/ 1.73 m2) without massive proteinuria
(urinary protein-creatinine ratio, UPCR <3.5) were retrospectively analyzed. aAG
was calculated from serum sodium, serum chloride, serum bicarbonate, serum
albumin, serum potassium, serum calcium and serum phosphate. The association
between the percentage of the 6-month change of eGFR (%DeltaeGFR/6m) and aAG was
examined. RESULTS: The mean baseline eGFR was 27.5 +/- 11.1 ml/min/1.73 m2 and
the mean %DeltaeGFR/6m was 13.8 +/- 10.3. UPCR and aAG were 1.13 +/- 0.93 and
9.48 +/- 1.88, respectively. %DeltaeGFR/6m was associated with aAG (r = 0.438, p
< 0.005), but not with UPCR (r = 0.194, p = 0.218). In multivariate linear
regression analyses, aAG remained significantly associated with %DeltaeGFR/6m
(beta = 0.45, p < 0.01) after controlling for age, baseline eGFR, UPCR and HCO3-
concentration. CONCLUSION: These data suggest that aAG appears to be associated
with the progression of CKD. aAG might be an independent predictor of CKD
progression.
PMID- 24348508
TI - Impact of Growth Hormone on Cystatin C.
AB - BACKGROUND: Cystatin C (CysC) is an alternative marker to creatinine for
estimation of the glomerular filtration rate (GFR). Hormones such as thyroid
hormones and glucocorticoids are known to have an impact on CysC. In this study,
we examined the effect of growth hormone (GH) on CysC in patients with acromegaly
undergoing transsphenoidal surgery. METHODS: Creatinine, CysC, GH and insulin
like growth factor-1 (IGF-1) were determined in 24 patients with acromegaly
before and following transsphenoidal surgery. Estimated GFR was calculated using
the Chronic Kidney Disease Epidemiology Collaboration formula. RESULTS: In all
patients, surgical debulking resulted in decreased clinical disease activity and
declining GH/IGF-1 levels. Postoperatively, biochemical cure was documented in 20
out of 24 patients. Creatinine levels (mean +/- SEM) increased from 72 +/- 3 to
80 +/- 3 umol/l (p = 0.0004) and concurrently, estimated GFR decreased from 99 +/
3 to 91 +/- 3 ml/min (p = 0.0008). In contrast to creatinine, CysC levels
decreased from 0.72 +/- 0.02 to 0.68 +/- 0.02 mg/l (p = 0.0008). CONCLUSIONS: Our
study provides strong evidence for discordant effects of GH on creatinine and
CysC in patients with acromegaly undergoing transsphenoidal surgery, thus
identifying another hormone that influences CysC independent of renal function.
PMID- 24348509
TI - Blobology: exploring raw genome data for contaminants, symbionts and parasites
using taxon-annotated GC-coverage plots.
AB - Generating the raw data for a de novo genome assembly project for a target
eukaryotic species is relatively easy. This democratization of access to large
scale data has allowed many research teams to plan to assemble the genomes of non
model organisms. These new genome targets are very different from the
traditional, inbred, laboratory-reared model organisms. They are often small, and
cannot be isolated free of their environment - whether ingested food, the
surrounding host organism of parasites, or commensal and symbiotic organisms
attached to or within the individuals sampled. Preparation of pure DNA
originating from a single species can be technically impossible, but assembly of
mixed-organism DNA can be difficult, as most genome assemblers perform poorly
when faced with multiple genomes in different stoichiometries. This class of
problem is common in metagenomic datasets that deliberately try to capture all
the genomes present in an environment, but replicon assembly is not often the
goal of such programs. Here we present an approach to extracting, from mixed DNA
sequence data, subsets that correspond to single species' genomes and thus
improving genome assembly. We use both numerical (proportion of GC bases and read
coverage) and biological (best-matching sequence in annotated databases)
indicators to aid partitioning of draft assembly contigs, and the reads that
contribute to those contigs, into distinct bins that can then be subjected to
rigorous, optimized assembly, through the use of taxon-annotated GC-coverage
plots (TAGC plots). We also present Blobsplorer, a tool that aids exploration and
selection of subsets from TAGC-annotated data. Partitioning the data in this way
can rescue poorly assembled genomes, and reveal unexpected symbionts and
commensals in eukaryotic genome projects. The TAGC plot pipeline script is
available from https://github.com/blaxterlab/blobology, and the Blobsplorer tool
from https://github.com/mojones/Blobsplorer.
PMID- 24348510
TI - Aberrant epigenetic regulators control expansion of human CD34+ hematopoietic
stem/progenitor cells.
AB - Transcription is a tightly regulated process ensuring the proper expression of
numerous genes regulating all aspects of cellular behavior. Transcription factors
regulate multiple genes including other transcription factors that together
control a highly complex gene network. The transcriptional machinery can be
"hijacked" by oncogenic transcription factors, thereby leading to malignant cell
transformation. Oncogenic transcription factors manipulate a variety of
epigenetic control mechanisms to fulfill gene regulatory and cell transforming
functions. These factors assemble epigenetic regulators at target gene promoter
sequences, thereby disturbing physiological gene expression patterns. Retroviral
vector technology and the availability of "healthy" human hematopoietic CD34+
progenitor cells enable the generation of pre-leukemic cell models for the
analysis of aberrant human hematopoietic progenitor cell expansion mediated by
leukemogenic transcription factors. This review summarizes recent findings
regarding the mechanism by which leukemogenic gene products control human
hematopoietic CD34+ progenitor cell expansion by disrupting the normal epigenetic
program.
PMID- 24348512
TI - Stem cells supporting other stem cells.
AB - Adult stem cell therapies are increasingly prevalent for the treatment of damaged
or diseased tissues, but most of the improvements observed to date are attributed
to the ability of stem cells to produce paracrine factors that have a trophic
effect on existing tissue cells, improving their functional capacity. It is now
clear that this ability to produce trophic factors is a normal and necessary
function for some stem cell populations. In vivo adult stem cells are thought to
self-renew due to local signals from the microenvironment where they live, the
niche. Several niches have now been identified which harbor multiple stem cell
populations. In three of these niches - the Drosophila testis, the bulge of the
mammalian hair follicle, and the mammalian bone marrow - one type of stem cell
has been found to produce factors that contribute to the maintenance of a second
stem cell population in the shared niche. In this review, I will examine the
architecture of these three niches and discuss the molecular signals involved.
Together, these examples establish a new paradigm for stem cell behavior, that
stem cells can promote the maintenance of other stem cells.
PMID- 24348514
TI - Erratum: Transcription and replication result in distinct epigenetic marks
following repression of early gene expression.
PMID- 24348511
TI - Regulation of the transcriptome by ER stress: non-canonical mechanisms and
physiological consequences.
AB - The mammalian unfolded protein response (UPR) is propagated by three ER-resident
transmembrane proteins, each of which initiates a signaling cascade that
ultimately culminates in production of a transcriptional activator. The UPR was
originally characterized as a pathway for upregulating ER chaperones, and a
comprehensive body of subsequent work has shown that protein synthesis, folding,
oxidation, trafficking, and degradation are all transcriptionally enhanced by the
UPR. However, the global reach of the UPR extends to genes involved in diverse
physiological processes having seemingly little to do with ER protein folding,
and this includes a substantial number of mRNAs that are suppressed by stress
rather than stimulated. Through multiple non-canonical mechanisms emanating from
each of the UPR pathways, the cell dynamically regulates transcription and mRNA
degradation. Here we highlight these mechanisms and their increasingly
appreciated impact on physiological processes.
PMID- 24348513
TI - Epigenetic alteration and microRNA dysregulation in cancer.
AB - MicroRNAs (miRNAs) play pivotal roles in numerous biological processes, and their
dysregulation is a common feature of human cancer. Thanks to recent advances in
the analysis of the cancer epigenome, we now know that epigenetic alterations,
including aberrant DNA methylation and histone modifications, are major causes of
miRNA dysregulation in cancer. Moreover, the list of miRNA genes silenced in
association with CpG island hypermethylation is rapidly growing, and various
oncogenic miRNAs are now known to be upregulated via DNA hypomethylation. Histone
modifications also play important roles in the dysregulation of miRNAs, and
histone deacetylation and gain of repressive histone marks are strongly
associated with miRNA gene silencing. Conversely, miRNA dysregulation is causally
related to epigenetic alterations in cancer. Thus aberrant methylation of miRNA
genes is a potentially useful biomarker for detecting cancer and predicting its
outcome. Given that many of the silenced miRNAs appear to act as tumor
suppressors through the targeting of oncogenes, re-expression of the miRNAs could
be an effective approach to cancer therapy, and unraveling the relationship
between epigenetic alteration and miRNA dysregulation may lead to the discovery
of new therapeutic targets.
PMID- 24348515
TI - Gene genealogies for genetic association mapping, with application to Crohn's
disease.
AB - A gene genealogy describes relationships among haplotypes sampled from a
population. Knowledge of the gene genealogy for a set of haplotypes is useful for
estimation of population genetic parameters and it also has potential application
in finding disease-predisposing genetic variants. As the true gene genealogy is
unknown, Markov chain Monte Carlo (MCMC) approaches have been used to sample
genealogies conditional on data at multiple genetic markers. We previously
implemented an MCMC algorithm to sample from an approximation to the distribution
of the gene genealogy conditional on haplotype data. Our approach samples
ancestral trees, recombination and mutation rates at a genomic focal point. In
this work, we describe how our sampler can be used to find disease-predisposing
genetic variants in samples of cases and controls. We use a tree-based
association statistic that quantifies the degree to which case haplotypes are
more closely related to each other around the focal point than control
haplotypes, without relying on a disease model. As the ancestral tree is a latent
variable, so is the tree-based association statistic. We show how the sampler can
be used to estimate the posterior distribution of the latent test statistic and
corresponding latent p-values, which together comprise a fuzzy p-value. We
illustrate the approach on a publicly-available dataset from a study of Crohn's
disease that consists of genotypes at multiple SNP markers in a small genomic
region. We estimate the posterior distribution of the tree-based association
statistic and the recombination rate at multiple focal points in the region.
Reassuringly, the posterior mean recombination rates estimated at the different
focal points are consistent with previously published estimates. The tree-based
association approach finds multiple sub-regions where the case haplotypes are
more genetically related than the control haplotypes, and that there may be one
or multiple disease-predisposing loci.
PMID- 24348516
TI - The role of mesenchymal stem cells in cancer development.
AB - The role of mesenchymal stem cells (MSCs) in cancer development is still
controversial. MSCs may promote tumor progression through immune modulation, but
other tumor suppressive effects of MSCs have also beendescribed. The discrepancy
between these results may arise from issues related to different tissue sources,
individual donor variability, and injection timing of MSCs. The expression of
critical receptors such as Toll-like receptor is variable a teach time point of
treatment, which may also determine the effects of MSCs on tumor progression.
However, factors released from malignant cells, as well as surrounding tissues
and the vasculature, are still regarded as a "black box. " Thus, it is still
difficult to clarify the specific role of MSCs in cancer development. Whether
MSCs support or suppress tumor progression is currently unclear, but it is clear
that systemically administered MSCs can be recruited and migrate toward tumors.
These findings are important because they can be used as a basis for initiating
studies to explore the incorporation of engineered MSCs as novel anti-tumor
carriers, for the development of tumor-targeted therapies.
PMID- 24348517
TI - On protocols and measures for the validation of supervised methods for the
inference of biological networks.
AB - Networks provide a natural representation of molecular biology knowledge, in
particular to model relationships between biological entities such as genes,
proteins, drugs, or diseases. Because of the effort, the cost, or the lack of the
experiments necessary for the elucidation of these networks, computational
approaches for network inference have been frequently investigated in the
literature. In this paper, we examine the assessment of supervised network
inference. Supervised inference is based on machine learning techniques that
infer the network from a training sample of known interacting and possibly non
interacting entities and additional measurement data. While these methods are
very effective, their reliable validation in silico poses a challenge, since both
prediction and validation need to be performed on the basis of the same partially
known network. Cross-validation techniques need to be specifically adapted to
classification problems on pairs of objects. We perform a critical review and
assessment of protocols and measures proposed in the literature and derive
specific guidelines how to best exploit and evaluate machine learning techniques
for network inference. Through theoretical considerations and in silico
experiments, we analyze in depth how important factors influence the outcome of
performance estimation. These factors include the amount of information available
for the interacting entities, the sparsity and topology of biological networks,
and the lack of experimentally verified non-interacting pairs.
PMID- 24348518
TI - Discovering epistasis in large scale genetic association studies by exploiting
graphics cards.
AB - Despite the enormous investments made in collecting DNA samples and generating
germline variation data across thousands of individuals in modern genome-wide
association studies (GWAS), progress has been frustratingly slow in explaining
much of the heritability in common disease. Today's paradigm of testing
independent hypotheses on each single nucleotide polymorphism (SNP) marker is
unlikely to adequately reflect the complex biological processes in disease risk.
Alternatively, modeling risk as an ensemble of SNPs that act in concert in a
pathway, and/or interact non-additively on log risk for example, may be a more
sensible way to approach gene mapping in modern studies. Implementing such
analyzes genome-wide can quickly become intractable due to the fact that even
modest size SNP panels on modern genotype arrays (500k markers) pose a
combinatorial nightmare, require tens of billions of models to be tested for
evidence of interaction. In this article, we provide an in-depth analysis of
programs that have been developed to explicitly overcome these enormous
computational barriers through the use of processors on graphics cards known as
Graphics Processing Units (GPU). We include tutorials on GPU technology, which
will convey why they are growing in appeal with today's numerical scientists. One
obvious advantage is the impressive density of microprocessor cores that are
available on only a single GPU. Whereas high end servers feature up to 24 Intel
or AMD CPU cores, the latest GPU offerings from nVidia feature over 2600 cores.
Each compute node may be outfitted with up to 4 GPU devices. Success on GPUs
varies across problems. However, epistasis screens fare well due to the high
degree of parallelism exposed in these problems. Papers that we review routinely
report GPU speedups of over two orders of magnitude (>100x) over standard CPU
implementations.
PMID- 24348519
TI - EMR-linked GWAS study: investigation of variation landscape of loci for body mass
index in children.
AB - Common variations at the loci harboring the fat mass and obesity gene (FTO),
MC4R, and TMEM18 are consistently reported as being associated with obesity and
body mass index (BMI) especially in adult population. In order to confirm this
effect in pediatric population five European ancestry cohorts from pediatric
eMERGE-II network (CCHMC-BCH) were evaluated. METHOD: Data on 5049 samples of
European ancestry were obtained from the Electronic Medical Records (EMRs) of two
large academic centers in five different genotyped cohorts. For all available
samples, gender, age, height, and weight were collected and BMI was calculated.
To account for age and sex differences in BMI, BMI z-scores were generated using
2000 Centers of Disease Control and Prevention (CDC) growth charts. A Genome-wide
association study (GWAS) was performed with BMI z-score. After removing missing
data and outliers based on principal components (PC) analyses, 2860 samples were
used for the GWAS study. The association between each single nucleotide
polymorphism (SNP) and BMI was tested using linear regression adjusting for age,
gender, and PC by cohort. The effects of SNPs were modeled assuming additive,
recessive, and dominant effects of the minor allele. Meta-analysis was conducted
using a weighted z-score approach. RESULTS: The mean age of subjects was 9.8
years (range 2-19). The proportion of male subjects was 56%. In these cohorts,
14% of samples had a BMI >=95 and 28 >= 85%. Meta analyses produced a signal at
16q12 genomic region with the best result of p = 1.43 * 10(-) (7) [p (rec) = 7.34
* 10(-) (8)) for the SNP rs8050136 at the first intron of FTO gene (z = 5.26) and
with no heterogeneity between cohorts (p = 0.77). Under a recessive model,
another published SNP at this locus, rs1421085, generates the best result [z =
5.782, p (rec) = 8.21 * 10(-) (9)]. Imputation in this region using dense 1000
Genome and Hapmap CEU samples revealed 71 SNPs with p < 10(-) (6), all at the
first intron of FTO locus. When hetero-geneity was permitted between cohorts,
signals were also obtained in other previously identified loci, including MC4R
(rs12964056, p = 6.87 * 10(-) (7), z = -4.98), cholecystokinin CCK (rs8192472, p
= 1.33 * 10(-) (6), z = -4.85), Interleukin 15 (rs2099884, p = 1.27 * 10(-) (5),
z = 4.34), low density lipoprotein receptor-related protein 1B [LRP1B (rs7583748,
p = 0.00013, z = -3.81)] and near transmembrane protein 18 (TMEM18) (rs7561317, p
= 0.001, z = -3.17). We also detected a novel locus at chromosome 3 at COL6A5
[best SNP = rs1542829, minor allele frequency (MAF) of 5% p = 4.35 * 10(-) (9), z
= 5.89]. CONCLUSION: An EMR linked cohort study demonstrates that the BMI-Z
measurements can be successfully extracted and linked to genomic data with
meaningful confirmatory results. We verified the high prevalence of childhood
rate of overweight and obesity in our cohort (28%). In addition, our data
indicate that genetic variants in the first intron of FTO, a known adult genetic
risk factor for BMI, are also robustly associated with BMI in pediatric
population.
PMID- 24348520
TI - Microrefugia and species persistence in the Galapagos highlands: a 26,000-year
paleoecological perspective.
AB - The Galapagos Islands are known to have experienced significant drought during
the Quaternary. The loss of mesophytic upland habitats has been suggested to
underlie the relatively lower endemism of upland compared with lowland plant
assemblages. A fossil pollen record spanning the last 26,000 years from an upland
bog on Santa Cruz Island, revealed the persistent presence of highland pollen and
spore types during the last glacial maximum and a millennial-scale series of
droughts in the mid Holocene. The absence of lowland taxa and presence of mesic
taxa led to the conclusion that the highland flora of the Galapagos persisted
during both these periods. The resiliency of the highland flora of the Galapagos
to long-term drought contradicts an earlier hypothesis that an extinction of
highland taxa occurred during the last glacial maximum and that rapid Holocene
speciation created the modern plant assemblage within the last 10,000 years.
Based on the palynological data, we suggest that, even during the height of
glacial and Holocene droughts, cool sea-surface temperatures and strong trade
wind activity would have promoted persistent ground level cloudiness that
provided the necessary moisture inputs to maintain microrefugia for mesophytic
plants. Although moist conditions were maintained, the lack of precipitation
caused the loss of open water habitat during such events, and accounts for the
known extinctions of species such as Azolla sp., and Elatine sp., while other
moisture dependent taxa, i.e., Cyathea weatherbyana, persisted.
PMID- 24348521
TI - Disruption of the expression and function of microRNAs in lung cancer as a result
of epigenetic changes.
AB - Two decades have passed since the discovery of microRNA (miRNA), which determines
cell fate in nematodes. About one decade ago, the conservation of miRNA in humans
was also discovered. At present, the loss of certain miRNAs and the
overexpression of miRNAs have been demonstrated in many types of diseases,
especially cancer. A key miRNA in lung cancer was reported soon after the initial
discovery of a tumor-suppressive miRNA in a hematological malignancy. Various
causes of miRNA disruption are known, including deletions, mutations, and
epigenetic suppression as well as coding genes. The recent accumulation of
knowledge regarding epigenetic transcriptional suppression has revealed the
suppression of several miRNAs in lung cancer in response to epigenetic changes,
such as H3K9 methylation prior to DNA methylation and H3K27 methylation
independent of DNA methylation. In this review, recent knowledge of miRNA
disruption in lung cancer as a result of epigenetic changes is discussed.
Additionally, emerging cancer-specific changes in RNA editing and their impact on
miRNA function are described.
PMID- 24348522
TI - PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries.
AB - Brain and spinal cord injuries initiate widespread temporal and spatial
neurodegeneration, through both necrotic and programmed cell death mechanisms.
Inflammation, reactive oxidation, excitotoxicity and cell-specific dysregulation
of metabolic processes are instigated by traumatic insult and are main
contributors to this cumulative damage. Successful treatments rely on prevention
or reduction of the magnitude of disruption, and interfering with injurious
cellular responses through modulation of signaling cascades is an effective
approach. Two intracellular signaling pathways, the phosphatase and tensin
homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein
kinase (MAPK) signaling cascades play various cellular roles under normal and
pathological conditions. Activation of both pathways can influence anatomical and
functional outcomes in multiple CNS disorders. However, some mechanisms involve
inhibiting or enhancing one pathway or the other, or both, in propagating
specific downstream effects. Though many intracellular mechanisms contribute to
cell responses to insult, this review examines the evidence exploring PTEN/PI3K
and MAPK signaling influence on pathology, neuroprotection, and repair and how
these pathways may be targeted for advancing knowledge and improving neurological
outcome after injury to the brain and spinal cord.
PMID- 24348523
TI - The perinucleolar compartment associates with malignancy.
AB - The perinucleolar compartment (PNC) is a unique nuclear substructure, forming
predominantly in cancer cells both in vitro and in vivo. PNC prevalence
(percentage of cells containing at least one PNC) has been found to positively
correlate with disease progression in several cancers (breast, ovarian, and
colon). While there is a clear association between PNCs and cancer, the molecular
function of the PNC remains unclear. Here we summarize the current understanding
of the association of PNCs with cancer and its possible functions in cancer
cells.
PMID- 24348524
TI - Eddy covariance VOC emission and deposition fluxes above grassland using PTR-TOF.
AB - Eddy covariance (EC) is the preferable technique for flux measurements since it
is the only direct flux determination method. It requires a continuum of high
time resolution measurements (e.g. 5-20 Hz). For volatile organic compounds (VOC)
soft ionization via proton transfer reaction has proven to be a quantitative
method for real time mass spectrometry; here we use a proton transfer reaction
time of flight mass spectrometer (PTR-TOF) for 10 Hz EC measurements of full mass
spectra up to m/z 315. The mass resolution of the PTR-TOF enabled the
identification of chemical formulas and separation of oxygenated and hydrocarbon
species exhibiting the same nominal mass. We determined 481 ion mass peaks from
ambient air concentration above a managed, temperate mountain grassland in
Neustift, Stubai Valley, Austria. During harvesting we found significant fluxes
of 18 compounds distributed over 43 ions, including protonated parent compounds,
as well as their isotopes and fragments and VOC-H+ - water clusters. The dominant
BVOC fluxes were methanol, acetaldehyde, ethanol, hexenal and other C6 leaf wound
compounds, acetone, acetic acid, monoterpenes and sequiterpenes. The smallest
reliable fluxes we determined were less than 0.1 nmol m-2 s-1, as in the case of
sesquiterpene emissions from freshly cut grass. Terpenoids, including mono- and
sesquiterpenes, were also deposited to the grassland before and after the
harvesting. During cutting, total VOC emission fluxes up to 200 nmolC m-2 s-1
were measured. Methanol emissions accounted for half of the emissions of
oxygenated VOCs and a third of the carbon of all measured VOC emissions during
harvesting.
PMID- 24348525
TI - Summertime elemental mercury exchange of temperate grasslands on an ecosystem
scale.
AB - In order to estimate the air-surface mercury exchange of grasslands in temperate
climate regions, fluxes of gaseous elemental mercury (GEM) were measured at two
sites in Switzerland and one in Austria during summer 2006. Two classic
micrometeorological methods (aerodynamic and modified Bowen ratio) have been
applied to estimate net GEM exchange rates and to determine the response of the
GEM flux to changes in environmental conditions (e.g. heavy rain, summer ozone)
on an ecosystem-scale. Both methods proved to be appropriate to estimate fluxes
on time scales of a few hours and longer. Average dry deposition rates up to 4.3
ng m-2 h-1 and mean deposition velocities up to 0.10 cm s-1 were measured, which
indicates that during the active vegetation period temperate grasslands are a
small net sink for atmospheric mercury. With increasing ozone concentrations
depletion of GEM was observed, but could not be quantified from the flux signal.
Night-time deposition fluxes of GEM were measured and seem to be the result of
mercury co-deposition with condensing water. Effects of grass cuts could also be
observed, but were of minor magnitude.
PMID- 24348526
TI - Comparison of User-Directed and Automatic Mapping of the Planned Isocenter to
Treatment Space for Prostate IGRT.
AB - Image-guided radiotherapy (IGRT), adaptive radiotherapy (ART), and online
reoptimization rely on accurate mapping of the radiation beam isocenter(s) from
planning to treatment space. This mapping involves rigid and/or nonrigid
registration of planning (pCT) and intratreatment (tCT) CT images. The purpose of
this study was to retrospectively compare a fully automatic approach, including a
non-rigid step, against a user-directed rigid method implemented in a clinical
IGRT protocol for prostate cancer. Isocenters resulting from automatic and
clinical mappings were compared to reference isocenters carefully determined in
each tCT. Comparison was based on displacements from the reference isocenters and
prostate dose-volume histograms (DVHs). Ten patients with a total of 243 tCTs
were investigated. Fully automatic registration was found to be as accurate as
the clinical protocol but more precise for all patients. The average of the
unsigned x, y, and z offsets and the standard deviations ( sigma ) of the signed
offsets computed over all images were (avg. +/- sigma (mm)): 1.1 +/- 1.4, 1.8
+/- 2.3, 2.5 +/- 3.5 for the clinical protocol and 0.6 +/- 0.8, 1.1 +/- 1.5 and
1.1 +/- 1.4 for the automatic method. No failures or outliers from automatic
mapping were observed, while 8 outliers occurred for the clinical protocol.
PMID- 24348527
TI - An overview of Bayesian methods for neural spike train analysis.
AB - Neural spike train analysis is an important task in computational neuroscience
which aims to understand neural mechanisms and gain insights into neural
circuits. With the advancement of multielectrode recording and imaging
technologies, it has become increasingly demanding to develop statistical tools
for analyzing large neuronal ensemble spike activity. Here we present a tutorial
overview of Bayesian methods and their representative applications in neural
spike train analysis, at both single neuron and population levels. On the
theoretical side, we focus on various approximate Bayesian inference techniques
as applied to latent state and parameter estimation. On the application side, the
topics include spike sorting, tuning curve estimation, neural encoding and
decoding, deconvolution of spike trains from calcium imaging signals, and
inference of neuronal functional connectivity and synchrony. Some research
challenges and opportunities for neural spike train analysis are discussed.
PMID- 24348528
TI - New and safe treatment of food impacted in the esophagus: a single center
experience of 100 consecutive cases.
AB - Aim. Large food bits can get stuck in the esophagus and must be removed by
endoscopy. In some cases, this can be difficult or unsafe. We describe a new and
safe treatment for such patients. Materials and Methods. 100 consecutive patients
were referred to Akershus University Hospital with impacted food in the
esophagus. In 36 patients (36%), the food passed spontaneously. In 59 (92%) of
the remaining 64 patients, the food was removed by endoscopic intervention. In
the last five patients, endoscopic removal was judged difficult or unsafe. These
patients received the new treatment: one capsule Creon 10000 IU dissolved in 30
mL of Coca-Cola administered by a nasooesophageal tube four times daily for 2-3
days. Results. Of the 59 patients treated with endoscopic procedure,
complications occurred in four (7%): three bleedings and one perforation of the
esophagus. In five patients treated with Coca-Cola and Creon, the food had either
passed or was soft after 2-3 days and could easily be removed. Conclusion. The
treatment of choice of impacted food in the esophagus is endoscopic removal. In
cases where this is difficult, we recommend treatment with Coca-Cola and Creon
for 2-3 days before complications occur.
PMID- 24348529
TI - Parenteral nutrition-induced cholestasis in neonates: where does the problem lie?
AB - Background. Parenteral nutrition (PN) is an effective method of nourishing the
neonate who is unable to receive full enteral feeds. Cholestasis can be a
complication of PN and can lead to severe liver damage. Aim. We describe our
patient population and determine risk factors for developing PN cholestasis.
Methods. Retrospective chart review of newborns admitted from January 2006 to May
2011 to the Neonatal Intensive Care Unit at our institution and received PN >14
days. Cholestasis was defined as serum conjugated bilirubin >50 MU mol/L.
Results. Eighty-seven newborns were included; 18 (20.7%) developed PN
cholestasis. The most frequent surgical condition for both groups was
gastroschisis (8/87; 9.2%). No significant differences were found between the
cholestasis and control groups for the following parameters: birth weight,
gestational age, intrauterine growth restriction, Apgar scores, and day of life
at initiation of enteral feeds. Duration of PN in days and dosage of
carbohydrates in g/kg/day were significantly higher in the cholestasis group than
the control group. Conclusion. PN-related cholestasis presented in one-fifth of
neonates receiving PN for more than two weeks. Longer duration of PN and higher
dosage of carbohydrates were independent risk factors for the development of PN
cholestasis in this population.
PMID- 24348531
TI - How to differentiate sites of gastrointestinal bleeding in patients with
hematochezia by using clinical factors?
AB - Hematochezia is one of common gastrointestinal complaint at the Emergency
Department (ED). Causes may be due to upper (UGIB) or lower (LGIB)
gastrointestinal tract bleeding. Here, clinical factors were studied to
differentiate sites of bleeding in patients with hematochezia. All patients with
an age of more than 18 years who were diagnosed with GIB at the ED, Ramathibodi
Hospital, Thailand were enrolled. Patients who presented with hematochezia and
received complete workups to identify causes of bleeding were studied and
categorized as being in the UGIB or LGIB groups. There were 1,854 patients who
presented with GIB at the ED. Of those, 76 patients presented with hematochezia;
30 patients were in the UGIB group, while 43 patients were in the LGIB group.
Clinical variables between both groups were mostly comparable. Three clinical
factors were significantly associated with UGIB causes in patients with
hematochezia including systolic blood pressure, hematocrit level, and BUN/Cr
ratio. The adjusted odds ratios for all three factors were 0.725 (per 5 mmHg
increase), 0.751 (per 3% increase), and 1.11 (per unit increase). Physicians at
the ED could use these clinical factors as a guide for further investigation in
patients who presented with hematochezia.
PMID- 24348532
TI - Prognostic Significance of DR-70 Levels in Dysplastic Colorectal Polyps.
AB - Background. To investigate the relationship between DR-70 serum levels and
dysplastic colon polyps. Materials and Methods. A total of 130 patients with
adenomatous polyps detected by colonoscopy and divided into two groups including
low versus high grade polyp, along with 50 healthy blood donors were included in
the study. Blood samples from each participant were analyzed for serum CEA and DR
70 levels. Results. No statistically significant differences were observed
between the two groups in terms of age or gender. The median DR-70 level was 0.5
MU g/mL in the healthy control group and 1.1 MU g/mL in group 1b (i.e., the high
grade polyp) (P < 0.001). DR-70 was higher in group 1b as compared to group 1a (P
< 0.001). However, the median DR-70 values for the low grade polyp group (i.e.,
group 1a) and the control group were similar (P = 0.067). In order to determine
independent predictors of high grade dysplasia, CEA, DR-70, polyp size, and age
parameters were subjected to multiple logistical regression analyses via the
Enter method; the model was statistically significant (P < 0.001). Conclusions.
DR-70, a marker used to measure FDP, which is generated by all major cancers, is
a potential marker to identify patients with advanced adenomatous polyps, that
is, precursors of colorectal cancer.
PMID- 24348530
TI - Nutrition care for patients with weight regain after bariatric surgery.
AB - Achieving optimal weight outcomes for patients with obesity is important to the
management of their chronic disease. All interventions present risks for weight
regain. Bariatric surgery is the most efficacious treatment, producing greater
weight losses that are sustained over more time compared to lifestyle
interventions. However, approximately 20-30% of patients do not achieve
successful weight outcomes, and patients may experience a regain of 20-25% of
their lost weight. This paper reviews several factors that influence weight
regain after bariatric surgery, including type of surgery, food tolerance, energy
requirements, drivers to eat, errors in estimating intake, adherence, food and
beverage choices, and patient knowledge. A comprehensive multidisciplinary
approach can provide the best care for patients with weight regain. Nutrition
care by a registered dietitian is recommended for all bariatric surgery patients.
Nutrition diagnoses and interventions are discussed. Regular monitoring of weight
status and early intervention may help prevent significant weight regain.
PMID- 24348533
TI - Preventive Effect of TU-100 on a Type-2 Model of Colitis in Mice: Possible
Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells.
AB - Purpose. Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of
inflammatory bowel disease (IBD), have histopathologically and immunologically
different characteristics. We previously reported that a traditional Japanese
medicine, daikenchuto (TU-100), ameliorated a trinitrobenzenesulfonic acid- (TNBS
) induced type-1 model colitis exhibiting histopathological features of CD
through adrenomedullin (ADM) enhancement. Our current aims were to examine
whether TU-100 ameliorates a type-2 model colitis that histologically resembles
UC and identify the active ingredients. Methods. TU-100 was administered orally
to mice with oxazolone- (OXN-) induced type-2 model colitis. The morbidity was
evaluated by body weight loss and the macroscopic score of colonic lesions. ADM
was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon
ulceration. ADM production by intestinal epithelial cells was increased by TU-100
addition. Screening to identify active ingredients showed that [6]-shogaol and
hydroxy alpha -sanshool enhanced ADM production. Conclusions. TU-100 exerted a
protective effect in OXN-induced type-2 model colitis, indicating that TU-100 may
be a beneficial agent for treatment of UC.
PMID- 24348534
TI - Helicobacter pylori Infection and Anemia in Taiwanese Adults.
AB - Background. Chronic Helicobacter pylori infection and iron-deficiency anemia
(IDA) are common in adults. Although the most common causes of IDA usually arise
from the gastrointestinal tract, the association between chronic Helicobacter
pylori infection and anemia remains unclear. Aim. To evaluate the association of
chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled
882 patients from January 2010 to April 2013. The status of Helicobacter pylori
(H.p) infection was confirmed and blood samples from the same participants were
taken on the same day to check the level of hemoglobin, serum iron, ferritin, and
total iron-binding capacity (TIBC). Results. No significant difference was noted
from the demographic data. The average level of hemoglobin (Hb) was not different
between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P =
0.699). Although the levels of serum IDA related parameters were expected in
positive group (lower serum iron and ferritin and higher TIBC) these differences
did not reach statistical significance (P = 0.824 for iron, P = 0.360 for
ferritin, and P = 0.252 for TIBC). Conclusion. Chronic Helicobacter pylori
infection is not attributed to IDA. The levels of hemoglobin, serum iron and
ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale
clinical studies are needed to prove the association.
PMID- 24348535
TI - International Consensus Diagnostic Criteria for Autoimmune Pancreatitis and Its
Japanese Amendment Have Improved Diagnostic Ability over Existing Criteria.
AB - Objectives. The recent International Consensus Diagnostic Criteria (ICDC) for
autoimmune pancreatitis (AIP) and its Japanese amendment developed by the
Japanese Pancreas Society (JPS 2011) may have overcome the drawbacks of earlier
criteria and achieved a higher diagnostic ability for AIP. The aim of the present
study is to evaluate this possibility and identify the underlying causes of this
change. Methods. We compared the diagnostic abilities of the ICDC and JPS 2011
with those of the Japanese diagnostic criteria 2006 (JPS 2006), Korean diagnostic
criteria (Korean), Asian diagnostic criteria (Asian), and HISORt diagnostic
criteria in 110 patients with AIP and 31 patients with malignant pancreatic
cancer. Results. The ICDC achieved the highest diagnostic ability in terms of
accuracy (95.0%), followed by JPS 2011 (92.9%), Korean (92.2%), HISORt (88.7%),
Asian (87.2%), and JPS 2006 (85.1%). Nearly all criteria systems exhibited a high
specificity of 100%, indicating that the enhanced diagnostic ability of the ICDC
and JPS 2011 likely stemmed from increased sensitivity brought about by inclusion
of diagnostic items requiring no endoscopic retrograde pancreatography. The
diagnostic ability of JPS 2011 was nearly equivalent to that of the ICDC.
Conclusions. The ICDC and JPS 2011 have improved diagnostic ability as compared
with earlier criteria sets because of an increase in sensitivity.
PMID- 24348536
TI - Insulin Resistance Increases MRI-Estimated Pancreatic Fat in Nonalcoholic Fatty
Liver Disease and Normal Controls.
AB - Background. Ectopic fat deposition in the pancreas and its relationship with
hepatic steatosis and insulin resistance have not been compared between patients
with nonalcoholic fatty liver disease (NAFLD) and healthy controls. Aim. Using a
novel magnetic resonance imaging (MRI) based biomarker, the proton-density-fat
fraction (MRI-PDFF), we compared pancreatic fat content in patients with biopsy
proven NAFLD to healthy controls and determined whether it is associated with
insulin resistance and liver fat content. Methods. This nested case-control study
was derived from two prospective studies including 43 patients with biopsy-proven
NAFLD and 49 healthy controls who underwent biochemical testing and MRI. Results.
Compared to healthy controls, patients with NAFLD had significantly higher
pancreatic MRI-PDFF (3.6% versus 8.5%, P value <0.001), and these results
remained consistent in multivariable-adjusted models including age, sex, body
mass index, and diabetes (P value =0.03). We found a strong correlation between
hepatic and pancreatic MRI-PDFF (Spearman correlation, P = 0.57, P value <0.001).
Participants with increased insulin resistance determined by homeostatic-model-of
insulin-resistance (HOMA-IR) greater than 2.5 had higher pancreatic (7.3% versus
4.5%, P value =0.015) and liver (13.5% versus 4.0%, P value <0.001) MRI-PDFF.
Conclusion. Patients with NAFLD have greater pancreatic fat than normal controls.
Insulin resistance is associated with liver and pancreatic fat accumulation.
PMID- 24348537
TI - Management of open abdomen: single center experience.
AB - Aim. The authors reviewed their experience in the management of open abdomen
using the vacuum-assisted closure (VAC), in order to assess its morbidity, and
the outcome of abdominal wall integrity. Methods. A retrospective review was
performed using the trauma registry to identify patients undergoing temporary
abdominal closure (TAC) either using Bogota Bag (BB) or VAC, from January 2006 to
December 2012. Inclusion criteria were TAC and survival to definitive abdominal
closure. Data collected included age, indication for TAC, number of operating
room procedures, primary fascial closure rate, and complications. Results. During
the study period, 156 patients required one type of TAC. Mean number of
operations required in BB group was 3.04 as compared to 1.96 in VAC group (P =
0.006). Survival was significantly increased in the VAC group (P < 0.001). The
difference in primary closure rates did not reach statistical significance (25%
vs. 55%; P = 0.074). Complications were observed less frequently in the VAC group
(P = 0.047). The mean time for fascial closure was 21 (+/-12) days in the BB
group, as opposed to 6 (+/-3) days in the VAC group (P < 0.001). Conclusion. The
vacuum assisted closure (VAC) has a significantly faster rate of closure,
requires less number of operations, and is associated with a lower complication
rate.
PMID- 24348538
TI - Enterovesical fistulae: aetiology, imaging, and management.
AB - Background and Study Objectives. Enterovesical fistula (EVF) is a devastating
complication of a variety of inflammatory and neoplastic diseases. Radiological
imaging plays a vital role in the diagnosis of EVF and is indispensable to
gastroenterologists and surgeons for choosing the correct therapeutic option.
This paper provides an overview of the diagnosis of enterovesical fistulae. The
treatment of fistulae is also briefly discussed. Material and Methods. We
performed a literature review by searching the Medline database for articles
published from its inception until September 2013 based on clinical relevance.
Electronic searches were limited to the keywords: "enterovesical fistula,"
"colovesical fistula" (CVF), "pelvic fistula", and "urinary fistula". Results.
EVF is a rare pathology. Diverticulitis is the commonest aetiology. Over two
thirds of affected patients describe pathognomonic features of pneumaturia,
fecaluria, and recurrent urinary tract infections. Computed tomography is the
modality of choice for the diagnosis of enterovesical fistulae as not only does
it detect a fistula, but it also provides information about the surrounding
anatomical structures. Conclusions. In the vast majority of cases, this condition
is diagnosed because of unremitting urinary symptoms after gastroenterologist
follow-up procedures for a diverticulitis or bowel inflammatory disease. Computed
tomography is the most sensitive test for enterovesical fistula.
PMID- 24348540
TI - Small intestinal tumours.
AB - Objective. Balloon enteroscopy (BE) and capsule enteroscopy (CE) are enteroscopy
methods that allow examination and treatment of the small bowel. Before the CE
and BE era, the small intestine was difficult to access for investigation. Small
intestinal tumours are infrequent conditions, but about half of them are
malignant. Materials and Methods. A total of 303 BEs were performed in 179
patients. Oral insertion was performed in 240 and anal in 63 BEs. Indications for
the procedure in our patients with small bowel tumours were anaemia and/or
bleeding, obstruction, suspicion of carcinoid tumour, or suspicion of Peutz
Jeghers syndrome. Results. In 50 of our 179 patients (28%), we diagnosed some
small intestinal tumours: hamartomas in Peutz-Jeghers syndrome in 16 patients,
adenocarcinoma in 7, lymphoma in 6, carcinoid tumour in 4, melanoma and stromal
tumour in 3, adenoma, lipoma, and inflammatory polyps in 2, and granular cell
tumour, cavernous lymphangioma, fibrolipoma, Cronkhite-Canada polyps, and
metastatic involvement in individual cases. Conclusion. BE facilitates
exploration and treatment of the small intestine. The procedure is generally safe
and useful. BE and CE are essential modalities for the management of small
intestinal diseases.
PMID- 24348539
TI - Dominant fecal microbiota in newly diagnosed untreated inflammatory bowel disease
patients.
AB - Our knowledge about the microbiota associated with the onset of IBD is limited.
The aim of our study was to investigate the correlation between IBD and the fecal
microbiota for early diagnosed untreated patients. The fecal samples used were a
part of the Inflammatory Bowel South-Eastern Norway II (IBSEN II) study and were
collected from CD patients (n = 30), UC patients (n = 33), unclassified IBD
(IBDU) patients (n = 3), and from a control group (n = 34). The bacteria
associated with the fecal samples were analyzed using a direct 16S rRNA gene
sequencing approach combined with a multivariate curve resolution (MCR) analysis.
In addition, a 16S rRNA gene clone library was prepared for the construction of
bacteria-specific gene-targeted single nucleotide primer extension (SNuPE)
probes. The MCR analysis resulted in the recovery of five pure components of the
dominant bacteria present: Escherichia/Shigella, Faecalibacterium, Bacteroides,
and two components of unclassified Clostridiales. Escherichia/Shigella was found
to be significantly increased in CD patients compared to control subjects, and
Faecalibacterium was found to be significantly reduced in CD patients compared to
both UC patients and control subjects. Furthermore, a SNuPE probe specific for
Escherichia/Shigella showed a significant overrepresentation of
Escherichia/Shigella in CD patients compared to control subjects. In conclusion,
samples from CD patients exhibited an increase in Escherichia/Shigella and a
decrease in Faecalibacterium indicating that the onset of the disease is
associated with an increase in proinflammatory and a decrease in anti
inflammatory bacteria.
PMID- 24348541
TI - Mast Cells Positive to Tryptase and c-Kit Receptor Expressing Cells Correlates
with Angiogenesis in Gastric Cancer Patients Surgically Treated.
AB - Background. Angiogenesis is a complex process involved in both growth and
progression of several human and animal tumours. Tryptase is a serin protease
stored in mast cells granules, which plays a role in tumour angiogenesis. Mast
cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation.
Method. In a series of 25 gastric cancer patients with stage T3N2-3M0 (by AJCC
for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods
were employed to evaluate in the tumour tissue the correlation between the number
of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC),
and microvascular density (MVD). Results. Data demonstrated a positive
correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the
mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean
number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and
MVD was significantly (r = 0.64, P = 0.001; r = 0.66, P = 0.041, resp.).
Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role
in gastric cancer angiogenesis, so we think that several c-KitR or tryptase
inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated
in clinical trials as a new antiangiogenetic approach.
PMID- 24348542
TI - Surgical treatment for achalasia of the esophagus: laparoscopic heller myotomy.
AB - Achalasia is an esophageal motility disorder that leads to dysphagia, chest pain,
and weight loss. Its diagnosis is clinically suspected and is confirmed with
esophageal manometry. Although pneumatic dilation has a role in the treatment of
patients with achalasia, laparoscopic Heller myotomy is considered by many
experts as the best treatment modality for most patients with newly diagnosed
achalasia. This review will focus on the surgical treatment of achalasia, with
special emphasis on laparoscopic Heller myotomy. We will also present a brief
discussion of the evaluation of patients with persistent or recurrent symptoms
after surgical treatment for achalasia and emerging technologies such as LESS,
robot-assisted myotomy, and POEM.
PMID- 24348543
TI - Clonality Analysis of Helicobacter pylori in Patients Isolated from Several
Biopsy Specimens and Gastric Juice in a Japanese Urban Population by Random
Amplified Polymorphic DNA Fingerprinting.
AB - Background. The number of Helicobacter pylori clones infecting a single host has
been discussed in numerous reports. The number has been suggested to vary
depending on the regions in the world. Aim. The purpose of this study was to
examine the number of clones infecting a single host in a Japanese urban
population. Materials and Methods. Thirty-one Japanese patients undergoing upper
gastrointestinal endoscopy were enrolled in this study. H. pylori isolates (total
104 strains) were obtained from biopsy specimens (antrum, corpus, and duodenum)
and gastric juice. Clonal diversity was examined by the random amplified
polymorphic DNA (RAPD) fingerprinting method. Results. The RAPD fingerprinting
patterns of isolates from each patient were identical or very similar. And the
isolates obtained from several patients with 5- to 9-year intervals showed
identical or very similar RAPD patterns. Conclusion. Each Japanese individual of
an urban population is predominantly infected with a single H. pylori clone.
PMID- 24348544
TI - Transabdominal ultrasonography of the small bowel.
AB - In the era of double balloon enteroscopy, capsule endoscopy, CT, and MRI
enterography is transabdominal ultrasonography (TUS) underestimated method for
evaluation of small bowel pathology. As often initial imagine method in abdominal
complaints, nowadays has TUS much better diagnostic potential than two decades
ago. High-resolution ultrasound probes with harmonic imaging significantly
improve resolution of bowel wall in real time, with possibility to asses bowel
peristalsis. Color flow doppler enables evaluation of intramural bowel
vascularisation, pulse wave doppler helps to quantificate flow in coeliac and
superior mesenteric arteries. Small intestine contrast ultrasonography with oral
contrast fluid, as well as contrast enhanced ultrasonography with intravenous
microbubble contrast also improves small bowel imaging. We present a review of
small intestine pathology that should be detected during ultrasound examinations,
discuss technical requirements, advantages and limitations of TUS, typical
ultrasound signs of Crohn's disease, ileus, celiac disease, intussusception,
infectious enteritis, tumours, ischemic and haemorrhagic conditions of small
bowel. In the hands of experienced investigator, despite some significant
limitations(obesity, meteorism), is transabdominal ultrasonography reliable,
noninvasive and inexpensive alternative method to computerised tomography (CT)
and magnetic resonance imaging (MRI) in small bowel examination.
PMID- 24348545
TI - Improved outcome of biliary atresia with postoperative high-dose steroid.
AB - Objective. The dosage, duration, and the benefits of high-dose steroid treatment
and outcome in biliary atresia (BA) remain controversial. In this study, we
evaluated the impact of high-dose steroid therapy on the outcome of BA after the
Kasai procedure. Methods. Intravenous prednisolone administration was started 1
week after surgery, followed by 8 to 12 weeks of oral prednisolone. Total
bilirubin (TB) levels (3, 6, and 12 months after surgery), early onset of
cholangitis, and two-year native liver survival were evaluated. Results. 53.4%,
56.9%, and 58.1% of the patients in the high-dose steroid group were jaundice
free 3, 6, and 12 months after surgery, respectively; these values were
significantly higher than the 38.7%, 39.4%, and 43.3% of the low-dose steroid
group. One year after surgery, the incidence of cholangitis in the high-dose
group (32.0%) was lower than that in the low-dose group (48.0%). Infants with
native liver in the high-dose group had a better two-year survival compared to
those in the low-dose steroid group (53.7% versus 42.6%). Conclusions. The high
dose steroid protocol can reduce the incidence of cholangitis, increase the
jaundice-free rate, and improve two-year survival with native liver after the
Kasai operation.
PMID- 24348546
TI - A full bi-tensor neural tractography algorithm using the unscented Kalman filter.
AB - We describe a technique that uses tractography to visualize neural pathways in
human brains by extending an existing framework that uses overlapping Gaussian
tensors to model the signal. At each point on the fiber, an unscented Kalman
filter is used to find the most consistent direction as a mixture of previous
estimates and of the local model. In our previous framework, the diffusion
ellipsoid had a cylindrical shape, i.e., the diffusion tensor's second and third
eigenvalues were identical. In this paper, we extend the tensor representation so
that the diffusion tensor is represented by an arbitrary ellipsoid. Experiments
on synthetic data show a reduction in the angular error at fiber crossings and
branchings. Tests on in vivo data demonstrate the ability to trace fibers in
areas containing crossings or branchings, and the tests also confirm the
superiority of using a full tensor representation over the simplified model.
PMID- 24348547
TI - Antioxidative properties and inhibition of key enzymes relevant to type-2
diabetes and hypertension by essential oils from black pepper.
AB - The antioxidant properties and effect of essential oil of black pepper (Piper
guineense) seeds on alpha -amylase, alpha -glucosidase (key enzymes linked to
type-2 diabetes), and angiotensin-I converting enzyme (ACE) (key enzyme linked to
hypertension) were assessed. The essential oil was obtained by hydrodistillation
and dried with anhydrous Na2SO4, and the phenolic content, radical [1,1-diphenyl
2 picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)
(ABTS) and nitric oxide (NO)] scavenging abilities as well as the ferric reducing
antioxidant property (FRAP) and Fe(2+)-chelating ability of the essential oil
were investigated. Furthermore, the effect on alpha -amylase, alpha -glucosidase,
and ACE enzyme activities was also investigated. The characterization of the
constituents was done using GC. The essential oil scavenged DPPH*, NO*, and ABTS*
and chelated Fe(2+). alpha -Pinene, beta -pinene, cis-ocimene, myrcene, allo
ocimene, and 1,8-cineole were among the constituents identified by GC. The
essential oil inhibited alpha -amylase, alpha -glucosidase, and ACE enzyme
activities in concentration-dependent manners, though exhibiting a stronger
inhibition of alpha -glucosidase than alpha -amylase activities. Conclusively,
the phenolic content, antioxidant activity, and inhibition of alpha -amylase,
alpha -glucosidase, and angiotensin-1 converting enzyme activities by the
essential oil extract of black pepper could be part of the mechanism by which the
essential oil could manage and/or prevent type-2 diabetes and hypertension.
PMID- 24348548
TI - Acetaldehyde content and oxidative stress in the deleterious effects of alcohol
drinking on rat uterine horn.
AB - After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a
severe atrophy in the rat uteirne horn was observed, accompanied by significant
alterations in its epithelial cells. Microsomal pathway of acetaldehyde
production was slightly increased. Hydroxyl radicals were detected in the
cytosolic fraction, and this was attributed to participation of xanthine
oxidoreductase. They were also observed in the microsomal fraction in the
presence of NADPH generating system. No generation of 1-hydroxyethyl was
evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine
horn homogenates revealed a significant increase in the chemiluminiscence
emission due to ethanol exposure. In the animals repeatedly exposed to alcohol,
sulfhydryl content from uterine horn proteins was decreased, but no significant
changes were observed in the protein carbonyl content from the same samples.
Minor but significant decreasing changes were observed in the GSH content
accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant
finding was the diminished activity content of glutathione peroxidase. Results
suggest that acetaldehyde accumulation plus the oxidative stress may play an
additional effect to the alcohol-promoted hormonal changes in the uterus reported
by others after chronic exposure to alcohol.
PMID- 24348549
TI - Effect of Aqueous Stem Bark Extract of Khaya senegalensis on Some Biochemical,
Haematological, and Histopathological Parameters of Rats.
AB - The subchronic effect of aqueous stem bark extract of Khaya senegalensis on some
biochemical, haematological, and histopathological parameters of rats was
investigated. The rats were divided into six groups of five rats per group.
Groups I to VI were administered graded doses of 0, 400, 800, 1200, 1600, and
2000 mg/kg bw, respectively. The result of study revealed that administration of
the Khaya senegalensis for twenty-eight days at the experimental dose resulted in
significant (P < 0.05) increase in urea, electrolytes (Na(+), K(+)), and
creatinine levels. The extract also significantly (P < 0.05) increased serum
activity of ALT, AST, and ALP. The levels of protein, albumin, and bilirubin were
significantly changed when compared to their control values, but they were not
dose dependent. The hematological indices assayed in this study were not
significantly affected at the experimental dose when compared to the control
values. Histological studies of the liver showed cellular degeneration and
necrosis and bile duct hyperplasia and fibrosis with lymphocytic infiltration of
the hepatocyte, providing supportive evidence for discussing the biochemical
findings, indicative of functional derangement. The histological architecture of
the kidney and that of the heart were however preserved. The result of this study
indicates that the aqueous stem bark extract of K. senegalensis may affect the
cellular integrity of vital organs of the body.
PMID- 24348550
TI - Brown fat expresses adiponectin in humans.
AB - The presence of brown adipose tissue (BAT) in humans is unclear.
Pheochromocytomas (PHEO) are rare tumors of neuroectodermal origin which occur in
0.1-0.2% of patients with hypertension. We sought to evaluate the presence and
activity of BAT surrounding adrenal PHEO in a well-studied sample of 11 patients
who were diagnosed with PHEO and then underwent adrenalectomy. Areas of white fat
(WAT) and BAT surrounding PHEO were obtained by Laser Capture Microdissection for
analysis of uncoupling protein (UCP)-1 and adiponectin mRNA expression.
Adiponectin and UCP-1 mRNA levels were significantly higher in BAT than in WAT
(0.62 versus 0.15 and 362.4 versus 22.1, resp., P < 0.01 for both). Adiponectin
mRNA levels significantly correlated with urinary metanephrines (r = 0.76, P <
0.01), vanilly mandelic acid (VMA) (r = 0.95, P < 0.01), and serum adiponectin
levels (r = 0.95, P < 0.01). Serum adiponectin levels significantly decreased
(24.2 +/- 2 MU g/mL versus 18 +/- 11 MU g/mL, P < 0.01) after adrenalectomy in
PHEO subjects. This study provides the following findings: (1) BAT surrounding
PHEO expresses adiponectin and UCP-1 mRNA, (2) expression of adiponectin mRNA is
significantly higher in BAT than in WAT surrounding PHEO, and (3) catecholamines
and serum adiponectin levels significantly correlate with BAT UCP-1 and
adiponectin mRNA.
PMID- 24348551
TI - Analyzing the role of receptor internalization in the regulation of melanin
concentrating hormone signaling.
AB - The regulation of appetite is complex, though our understanding of the process is
improving. The potential role for the melanin-concentrating hormone (MCH)
signaling pathway in the treatment of obesity is being explored by many. It was
hypothesized that internalization of MCH receptors would act to potently
desensitize cells to MCH. Despite potent desensitization of ERK signaling by MCH
in BHK-570 cells, we were unable to observe MCH-mediated internalization of MCH
receptor 1 (MCHR1) by fluorescence microscopy. A more quantitative approach using
a cell-based ELISA indicated only 15% of receptors internalized, which is much
lower than that reported in the literature. When beta-arrestins were
overexpressed in our system, removal of receptors from the cell surface was
facilitated and signaling to a leptin promoter was diminished, suggesting that
internalization of MCHR1 is sensitive to cellular beta-arrestin levels. A
dominant-negative GRK construct completely inhibited loss of receptors from the
cell surface in response to MCH, suggesting that the internalization observed is
phosphorylation-dependent. Since desensitization of MCH-mediated ERK signaling
did not correlate with significant loss of MCHR1 from the cell surface, we
hypothesize that in this model system regulation of MCH signaling may be the
result of segregation of receptors from signaling components at the plasma
membrane.
PMID- 24348552
TI - Investigation of responsiveness to thyrotropin-releasing hormone in growth
hormone-producing pituitary adenomas.
AB - Objective. The aim of this study was to investigate how the paradoxical response
of GH secretion to TRH changes according to tumor volumes. Methods. Patients with
newly diagnosed acromegaly were classified as either TRH responders or
nonresponders according to the results of a TRH stimulation test (TST), and their
clinical characteristics were compared according to responsiveness to TRH and
tumor volumes. Results. A total of 41 acromegalic patients who underwent the TST
were included in this study. Between TRH responders and nonresponders, basal GH,
IGF-I levels, peak GH levels, and tumor volume were not significantly different,
but the between-group difference of GH levels remained near significant over the
entire TST time. DeltaGHmax-min during the TST were significantly different
according to the responsiveness to TRH. Peak GH levels and DeltaGHmax-min during
the TST showed significantly positive correlations with tumor volume with higher
levels in macroadenomas than in microadenomas. GH levels over the entire TST time
also remained significantly higher in macroadenomas than in microadenomas.
Conclusion. Our data demonstrated that the paradoxical response of GH secretion
to TRH in GH-producing pituitary adenomas was not inversely correlated with tumor
volumes.
PMID- 24348553
TI - Trunk fat negatively influences skeletal and testicular functions in obese men:
clinical implications for the aging male.
AB - Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and
insulin sensitivity. Evidence from male rodents suggests that OSCA may also
regulate testosterone (T) synthesis. Using a cross-sectional design, we evaluated
OSCA, 25(OH) vitamin D, T, 17 beta -estradiol (E2), homeostasis model assessment
of insulin resistance (HOMA-IR), and body composition in 86 obese (mean BMI = 34)
male subjects (18-69 yr old). Independently from BMI, an inverse relationship
between trunk fat percentage and plasma T (r (2) = -0.26, P < 0.01) and between
HOMA-IR and OSCA levels (r (2) = -0.22, P < 0.005) was found. OSCA levels, as
well as vitamin D, decreased significantly for higher BMI with significant
differences above 35 (P < 0.01). A direct correlation between T and bone mineral
density at lumbar (BMDL) and neck (BMDH) (P < 0.001, r (2) = -0.20; P < 0.001, r
(2) = -0.24) was found, independently from age. An inverse correlation between E2
levels, BMDL, and BMDH (P < 0.001, r (2) = -0.20; P < 0.001, r (2) = -0.19) was
observed. These data provide new evidences that a relationship between trunk fat
mass, insulin sensitivity, OSCA and T synthesis occurs. This new relationship
with skeletal health has relevant implications for the aging male, suggesting
OSCA as a novel marker of metabolic and gonadal health status.
PMID- 24348554
TI - Incidental thyroid carcinoma diagnosed after total thyroidectomy for benign
thyroid diseases: incidence and association with thyroid disease type and
laboratory markers.
AB - Objective. Currently, total thyroidectomy (TT) is widely used to treat benign
thyroid diseases and thyroid carcinoma. The differential diagnosis between benign
and malignant thyroid disorders and the potential identification of thyroid
microcarcinomas with biochemical markers remain controversial. This retrospective
study aimed to estimate the prognostic validity of thyroid autoantibodies,
thyroglobulin (Tg), and the thyroid disease type in diagnostic approaches
regarding the co-existence of incidental thyroid carcinoma (ITC) with benign
thyroid diseases. Methods. A cohort of 228 patients was treated with TT for
benign thyroid disorders between 2005 and 2010. Thyroid autoantibodies and Tg
were preoperatively estimated. Patients were classified according to the
preoperative and histologically established diagnoses, and the median values of
the biochemical markers were compared between the groups. Results. ITC was
detected in 33/228 patients and almost exclusively in the presence of nontoxic
thyroid disorders (P = 0.014). There were no statistically significant
differences in the median values of the biochemical markers between the benign
and malignant groups. There was also no significant association between ITC and
chronic lymphocytic thyroiditis. Conclusions. The co-existence of ITC with benign
and especially nontoxic thyroid diseases is significant, and treatment of these
disorders with TT when indicated can lead to the identification and definitive
cure of microcarcinomas. Further studies are required to establish precise
markers with prognostic validity for TC diagnosis.
PMID- 24348555
TI - Estrogen inhibits colon polyp formation by reducing angiogenesis in a carcinogen
induced rat model.
AB - Objective. To study the effects of estrogen on colon polyp formation,
proliferation, and angiogenesis on a rat model of colon cancer induced by
dimethylhydrazine (DMH). Methods. Thirty-six female ovariectomized (OVX) rats
were randomly divided into 3 groups: (I) control group (administrated with
vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH +
E2 group (administrated with DMH and 17beta-estradiol weekly). The incidence,
volumes, and multiplicity of colon polyps in each group were evaluated. The
microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen
(PCNA), and the expressions of HIF-1 alpha and VEGF in polyps were detected in
each group. Results. Estrogen reduced the multiplicity, volumes, and the PCNA
expressions of DMH-induced colon polyps. The MVD in DMH + E2 group was
significantly lower than that in DMH group. Estrogen treatment decreased the HIF
1 alpha and VEGF expressions at both mRNA and protein level. Conclusion. Estrogen
replacement was protective for ovariectomized rats from DMH-induced
carcinogenesis, and one of the mechanisms for this was due to estrogen's
inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1
alpha expressions.
PMID- 24348556
TI - Mitotane-induced hyperlipidemia: a retrospective cohort study.
AB - Limited data are available about mitotane-nduced hyperlipidemia. We
retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma
(ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and
clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL
c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively.
HDL-c, LDL-c, and triglyceride concentrations significantly increased with
mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL (P < 0.001), a mean LDL
peak of 160.1 mg/dL (P < 0.001), and a mean triglyceride peak (Tg-P) of 216.7
mg/dL (P = 0.042). HDL-P positively correlated with mitotane concentration (r =
0.52, P < 0.001), while LDL-P levels and Tg-P did not. Gender, body mass index,
cortisol overproduction, baseline levels of HDL-c, and triglyceride did not
predict change in HDL-c. Similar changes were noticed in subgroup analysis after
excluding patients who were using lipid-lowering agents. In conclusion, in ACC
patients, mitotane caused significant increases in HDL-c that may counteract the
deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the
mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs.
PMID- 24348557
TI - Potential mechanisms for racial and ethnic differences in antimullerian hormone
and ovarian reserve.
AB - Accumulating evidence suggests that reproductive potential and function may be
different across racial and ethnic groups. Racial differences have been
demonstrated in pubertal timing, infertility, outcomes after assisted
reproductive technology (ART) treatment, and reproductive aging. Recently, racial
differences have also been described in serum antimullerian hormone (AMH), a
sensitive biomarker of ovarian reserve, supporting the notion that ovarian
reserve differs between racial/ethnic groups. The existence of such racial/ethnic
differences in ovarian reserve, as reflected by AMH, may have important clinical
implications for reproductive endocrinologists. However, the mechanisms which may
underlie such racial differences in ovarian reserve are unclear. Various genetic
factors and environmental factors such as obesity, smoking, and vitamin D
deficiency which have been shown to correlate with serum AMH levels and also
display significant racial/ethnic variations are discussed in this review.
Improving our understanding of racial differences in ovarian reserve and their
underlying causes may be essential for infertility treatment in minority women
and lead to better reproductive planning, improved treatment outcomes, and timely
interventions which may prolong reproductive lifespan in these women.
PMID- 24348559
TI - Comparing health promotion programs in public dental service of vantaa, Finland:
a clinical trial in 6-36-month-old children.
AB - Objective. The study assessed whether the new family-based programs in health
promotion or the training of dental professionals had an impact on the
colonization of mutans streptococci (MS) in young children. Material and Methods.
The participants were children born in 2008 and inhabitants of Vantaa aged 24-36
months. The families with first-born children were invited to a questionnaire
study. Vantaa was categorized into three matching areas, which were randomly
assigned to different programs. New counseling methods were trained. The routine
program used earlier served as the control group. The children born in 2006
served as a historic control. The outcome measure was the presence of MS.
Statistical method was logistic regression. Results. Colonization of MS was found
only in few children born in 2006 or 2008; 15% and 11%, respectively. Within the
2008 birth cohort, the addition of parental counseling did not improve the
routine program. Instead, the father's advanced level of education (P = 0.044)
and the child's reported the use of xylitol at least three times a day (P =
0.014) associated with negative MS scores. Conclusions. The routine program and
training of the professionals seem to reduce the proportion of children with MS
more than adding parental self-care to oral health programs.
PMID- 24348558
TI - How Much Does AMH Really Vary in Normal Women?
AB - Anti-Mullerian Hormone (AMH) is an ovarian hormone expressed in growing follicles
that have undergone recruitment from the primordial follicle pool but have not
yet been selected for dominance. It is considered an accurate marker of ovarian
reserve, able to reflect the size of the ovarian follicular pool of a woman of
reproductive age. In comparison to other hormonal biomarkers such as serum FSH,
low intra- and intermenstrual cycle variability have been proposed for AMH. This
review summarizes the knowledge regarding within-subject variability, with
particular attention on AMH intracycle variability. Moreover the impact of
ethnicity, body mass index, and smoking behaviour on AMH interindividual
variability will be reviewed. Finally changes in AMH serum levels in two
conditions of ovarian quiescence, namely contraceptives use and pregnancy, will
be discussed. The present review aims at guiding researchers and clinicians in
interpreting AMH values and fluctuations in various research and clinical
scenarios.
PMID- 24348560
TI - Management of internal root resorption on permanent teeth.
AB - Internal root resorption (IRR) is a particular category of pulp disease
characterized by the loss of dentine as a result of the action of clastic cells
stimulated by pulpal inflammation. This review article explains the etiology, the
prevalence of IRR, and, in addition to the clinical data, the contribution of the
three-dimensional imaging (CBCT) to the diagnosis, the clinical decision, and the
therapeutic management of IRR. The authors discussed the various therapeutic
options including the orthograde or retrograde fillings of the root canal
resorption area. Root canal treatment remains the treatment of choice of internal
root resorption as it removes the granulation tissue and blood supply of the
clastic cells. The authors describe with different clinical cases the modern
endodontic techniques including optical aids, ultrasonic improvement of chemical
debridement, and the use of alternative materials such as calcium silicate
combined with thermoplastic filling (warm gutta-percha). In these conditions, the
prognosis of the conservative treatment of internal resorptions, even if root
walls are perforated, is good.
PMID- 24348561
TI - Alternative splicing: role in cancer development and progression.
PMID- 24348562
TI - Role of protein misfolding and proteostasis deficiency in protein misfolding
diseases and aging.
AB - The misfolding, aggregation, and tissue accumulation of proteins are common
events in diverse chronic diseases, known as protein misfolding disorders. Many
of these diseases are associated with aging, but the mechanism for this
connection is unknown. Recent evidence has shown that the formation and
accumulation of protein aggregates may be a process frequently occurring during
normal aging, but it is unknown whether protein misfolding is a cause or a
consequence of aging. To combat the formation of these misfolded aggregates cells
have developed complex and complementary pathways aiming to maintain protein
homeostasis. These protective pathways include the unfolded protein response, the
ubiquitin proteasome system, autophagy, and the encapsulation of damaged proteins
in aggresomes. In this paper we review the current knowledge on the role of
protein misfolding in disease and aging as well as the implication of
deficiencies in the proteostasis cellular pathways in these processes. It is
likely that further understanding of the mechanisms involved in protein
misfolding and the natural defense pathways may lead to novel strategies for
treatment of age-dependent protein misfolding disorders and perhaps aging itself.
PMID- 24348563
TI - The mitochondrial disulfide relay system: roles in oxidative protein folding and
beyond.
AB - Disulfide bond formation drives protein import of most proteins of the
mitochondrial intermembrane space (IMS). The main components of this disulfide
relay machinery are the oxidoreductase Mia40 and the sulfhydryl oxidase Erv1/ALR.
Their precise functions have been elucidated in molecular detail for the yeast
and human enzymes in vitro and in intact cells. However, we still lack knowledge
on how Mia40 and Erv1/ALR impact cellular and organism physiology and whether
they have functions beyond their role in disulfide bond formation. Here we
summarize the principles of oxidation-dependent protein import mediated by the
mitochondrial disulfide relay. We proceed by discussing recently described
functions of Mia40 in the hypoxia response and of ALR in influencing
mitochondrial morphology and its importance for tissue development and
embryogenesis. We also include a discussion of the still mysterious function of
Erv1/ALR in liver regeneration.
PMID- 24348564
TI - Cysteine-10 on 17 beta -Hydroxysteroid Dehydrogenase 1 Has Stabilizing
Interactions in the Cofactor Binding Region and Renders Sensitivity to Sulfhydryl
Modifying Chemicals.
AB - 17 beta -Hydroxysteroid dehydrogenase type 1 (17 beta -HSD1) catalyzes the
conversion of estrone to the potent estrogen estradiol. 17 beta -HSD1 is highly
expressed in breast and ovary tissues and represents a prognostic marker for the
tumor progression and survival of patients with breast cancer and other estrogen
dependent tumors. Therefore, the enzyme is considered a promising drug target
against estrogen-dependent cancers. For the development of novel inhibitors, an
improved understanding of the structure-function relationships is essential. In
the present study, we examined the role of a cysteine residue, Cys(10), in the
Rossmann-fold NADPH binding region, for 17 beta -HSD1 function and tested the
sensitivity towards sulfhydryl modifying chemicals. 3D structure modeling
revealed important interactions of Cys(10) with residues involved in the
stabilization of amino acids of the NADPH binding pocket. Analysis of enzyme
activity revealed that 17 beta -HSD1 was irreversibly inhibited by the sulfhydryl
modifying agents N-ethylmaleimide (NEM) and dithiocarbamates. Preincubation with
increasing concentrations of NADPH protected 17 beta -HSD1 from inhibition by
these chemicals. Cys(10)Ser mutant 17 beta -HSD1 was partially protected from
inhibition by NEM and dithiocarbamates, emphasizing the importance of Cys(10) in
the cofactor binding region. Substitution of Cys(10) with serine resulted in a
decreased protein half-life, without significantly altering kinetic properties.
Despite the fact that Cys(10) on 17 beta -HSD1 seems to have limited potential as
a target for new enzyme inhibitors, the present study provides new insight into
the structure-function relationships of this enzyme.
PMID- 24348566
TI - Agromyces arachidis sp. nov. Isolated from a Peanut (Arachis hypogaea) Crop
Field.
AB - A Gram-positive, yellowish bacterium strain AK-1(T) was isolated from soil sample
collected from peanut (Arachis hypogaea) crop field and studied by using a
polyphasic approach. The organism had morphological and chemotaxonomic properties
consistent with its classification in the genus Agromyces. Phylogenetic analysis
of the 16S rRNA gene sequence showed that strain AK-1(T) was closely related to
Agromyces aurantiacus (98.6%) followed by Agromyces soli (98.3%), Agromyces
tropicus (97.6%), Agromyces ulmi (97.3%), Agromyces flavus (97.2%), and Agromyces
italicus (97.0%), whereas the sequence similarity values with respect to the
other Agromyces species with validly published names were between 95.3 and 96.7
%. However, the DNA-DNA hybridization values obtained between strain AK-1(T) and
other related strains were well below the threshold that is required for the
proposal of a novel species. The DNA G + C content of the strain is 71.8 mol%.
The above data in combination with the phenotypic distinctiveness of AK-1(T)
clearly indicate that the strain represents a novel species, for which the name
Agromyces arachidis sp. nov. is proposed. The type strain is AK-1(T) (=MTCC
10524(T) = JCM 19251(T)).
PMID- 24348567
TI - Rheumatoid factor positivity is associated with increased joint destruction and
upregulation of matrix metalloproteinase 9 and cathepsin k gene expression in the
peripheral blood in rheumatoid arthritic patients treated with methotrexate.
AB - We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNF alpha
, matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of
rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to
their rheumatoid factor status, clinical, immunological, and radiological
parameters, and therapeutic response after a 24-month follow-up. The study group
consisted of 35 control subjects and 33 RA patients without previous history of
MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased
disease activity in patients at the end of the study was associated with
significant downregulation of TNF alpha expression. Downregulation of mTOR was
observed in seronegative patients, while no significant changes in the expression
of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study.
The increase in erosion numbers observed in the seropositive patients at the end
of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while
seronegative patients demonstrated an absence of significant changes in MMP-9 and
cathepsin K expression and no increase in the erosion score. Our results suggest
that increased expression of MMP-9 and cathepsin K genes in the peripheral blood
might indicate higher bone tissue destruction activity in RA patients treated
with methotrexate. The clinical study registration number is 0120.0810610.
PMID- 24348568
TI - Myomectomy during Caesarean Birth in Fibroid-Endemic, Low-Resource Settings.
AB - If myomectomy during caesarean delivery becomes a widespread practice, it could
potentially eliminate multiple surgeries for both indications. However, many
surgeons have been reluctant to adopt this policy without conclusive evidence
demonstrating its safety. This study reviews the publications on caesarean
myomectomy especially from the African Continent with respect to duration of
surgery, blood loss, length of hospital stay, and blood transfusions. Judging
from the lack of large studies on caesarean myomectomy, the proportion of
surgeons who attempt the procedure is largely low because of concerns about its
safety. However, most of the authors suggested that the complications and
morbidity following caesarean myomectomy do not significantly differ from those
occurring during caesarean section alone, while fertility is apparently not
compromised by this treatment. With careful patient selection, adequate
experience, and efficient haemostatic measures, the procedure does not appear as
hazardous as was once thought. This piece of information is relevant for
counseling women who request for the simultaneous removal of previously diagnosed
fibroids during caesarean section. Staff and facilities for safe management of
haemorrhage are a requisite for the procedure. Large randomized trials are needed
to guide decisions as to the best clinical practice regarding myomectomy during
caesarean delivery.
PMID- 24348569
TI - The natural history of uterine leiomyomas: light and electron microscopic studies
of fibroid phases, interstitial ischemia, inanosis, and reclamation.
AB - We propose, and offer evidence to support, the concept that many uterine
leiomyomas pursue a self-limited life cycle. This cycle can be arbitrarily
divided on the basis of morphologic assessment of the collagen content into 4
phases: (1) proliferation, (2) proliferation and synthesis of collagen, (3)
proliferation, synthesis of collagen, and early senescence, and (4) involution.
Involution occurs as a result of both vascular and interstitial ischemia.
Interstitial ischemia is the consequence of the excessive elaboration of
collagen, resulting in reduced microvascular density, increased distance between
myocytes and capillaries, nutritional deprivation, and myocyte atrophy. The end
stage of this process is an involuted tumor with a predominance of collagen,
little to no proliferative activity, myocyte atrophy, and myocyte cell death.
Since many of the dying cells exhibit light microscopic and ultrastructural
features that appear distinct from either necrosis or apoptosis, we refer to this
process as inanosis, because it appears that nutritional deprivation, or
inanition, is the underlying cause of cell death. The disposal of myocytes dying
by inanosis also differs in that there is no phagocytic reaction, but rather an
apparent dissolution of the cell, which might be viewed as a process of
reclamation as the molecular contents are reclaimed and recycled.
PMID- 24348565
TI - The role of s-nitrosylation and s-glutathionylation of protein disulphide
isomerase in protein misfolding and neurodegeneration.
AB - Neurodegenerative diseases involve the progressive loss of neurons, and a
pathological hallmark is the presence of abnormal inclusions containing misfolded
proteins. Although the precise molecular mechanisms triggering neurodegeneration
remain unclear, endoplasmic reticulum (ER) stress, elevated oxidative and
nitrosative stress, and protein misfolding are important features in
pathogenesis. Protein disulphide isomerase (PDI) is the prototype of a family of
molecular chaperones and foldases upregulated during ER stress that are
increasingly implicated in neurodegenerative diseases. PDI catalyzes the
rearrangement and formation of disulphide bonds, thus facilitating protein
folding, and in neurodegeneration may act to ameliorate the burden of protein
misfolding. However, an aberrant posttranslational modification of PDI, S
nitrosylation, inhibits its protective function in these conditions. S
nitrosylation is a redox-mediated modification that regulates protein function by
covalent addition of nitric oxide- (NO-) containing groups to cysteine residues.
Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI) in
neurodegeneration and how this may be linked to another aberrant modification of
PDI, S-glutathionylation. Understanding the role of aberrant S-nitrosylation/S
glutathionylation of PDI in the pathogenesis of neurodegenerative diseases may
provide insights into novel therapeutic interventions in the future.
PMID- 24348570
TI - Esophageal intramural pseudodiverticulosis: a rare endoscopic finding.
AB - A 76-year-old woman, presenting with a 4-year history of progressive dysphagia,
was submitted to endoscopic examination. The upper endoscopy revealed a proximal
esophageal stricture and inflammatory mucosa associated with multiples small
orifices in the esophageal wall, some of them fulfilled with white spots
suggestive of fungal infection. This was a typical endoscopic finding of
esophageal intramural pseudodiverticulosis, a benign and rare condition, related
to chronic esophagitis and others comorbid states, such as gastroesophageal
reflux disease or infectious esophagitis, diabetes mellitus, alcohol consumption,
and achalasia. Dysphagia is the predominant symptom and can be accompanied by
esophageal stricture in 80% to 90% of patients. The pathogenesis is unknown, and
as the pseudodiverticulosis is an intramural finding, endoscopy biopsies are
inconclusive. The main histological finding is dilation of the submucosal glands
excretory ducts, probably obstructed by inflammatory cells. The treatment
consists in management of the underlying diseases and symptoms relief. In this
particular case, the patient was submitted to antifungal drugs followed by
endoscopic dilation with thermoplastic bougies, with satisfactory improvement of
dysphagia.
PMID- 24348571
TI - Infliximab-Induced Hypothyroidism: A Novel Case and Postulations concerning the
Mechanism.
AB - We report a patient with cutaneous sarcoidosis who developed hypothyroidism
following 17 months of infliximab therapy. To our knowledge, this is the first
reported case of hypothyroidism following infliximab administration. While it is
possible that the patient's hypothyroidism was unrelated to the use of
infliximab, the time course and lack of alternative explanations make such an
association plausible. We postulate that hypothyroidism in this patient may have
been related to the development of autoantibodies to infliximab that triggered
the development of an autoimmune thyroiditis. Regardless of the mechanism, we
would encourage clinicians to keep the potential mechanisms of TNF-alpha in mind
when treating patients with TNF-alpha antagonist medications.
PMID- 24348572
TI - Kernohan's Notch: A Forgotten Cause of Hemiplegia-CT Scans Are Useful in This
Diagnosis.
AB - Hemiparesis ipsilateral to a cerebral lesion can be a false localizing sign. This
is due to midline shift of the midbrain resulting in compression of the
contralateral pyramidal fibers on the tough dural reflection tentorium cerebelli.
This may result in partial or complete damage to these fibers. Since these fibers
are destined to cross in the medulla and innervate the opposite side of the body,
this causes hemiparesis ipsilateral to the site of cerebral lesion. Computed
tomography (CT) scans have not been used to support the diagnosis of this entity
until now. We report a 68-year-old woman with a subdural hematoma who developed
ipsilateral hemiparesis without any other explanation (Kernohan's notch). The CT
of the head showed evidence of compression of the midbrain contralateral to the
hematoma and was useful in the diagnosis. The purpose of this report is to
increase the awareness of this presentation and to emphasize the utility of CT
scans to support the diagnosis.
PMID- 24348573
TI - Pneumomediastinum Complicating Diabetic Ketoacidosis and Boerhaave's Syndrome.
AB - An 18-year-old man presented with altered mental status. He was found to have
diabetic ketoacidosis. Chest X-ray showed pneumomediastinum. After intubation for
air-way protection, an oral-gastric tube was placed. A chest computed tomography
scan showed the tip of the oral-gastric tube to be in the right hemithorax. The
patient underwent a thoracotomy and was managed in the intensive care unit. Both
diabetic ketoacidosis and Boerhaave's syndrome should be considered as possible
causes of pneumomediastinum in a patient with similar presentation. Boerhaave's
syndrome should be ruled out prior to the insertion of an oral-gastric tube to
avoid further morbidities.
PMID- 24348574
TI - Mixed acinar-neuroendocrine carcinoma of the pancreas with neuroendocrine
predominance.
AB - Background. Pancreatic tumors are rare and could arise from either the exocrine
(ductal and acinar cells) or the endocrine (neuroendocrine cells) components of
the pancreas. In some instances, the occurrence of pancreatic tumors comprising
both acinar cells and neuroendocrine cells, with neuroendocrine cells making up
more than 30% of the tumor, has been identified. This unique entity has been
referred to as mixed acinar-neuroendocrine carcinoma (MANEC). Only about 20 such
cases have been reported in the literature. Case Report. We report an interesting
case of MANEC with neuroendocrine cell predominance in a woman presenting with
epigastric pain secondary to a pancreatic mass with acinar and endocrine
differentiation. She underwent surgical resection of the tumor and was offered
adjuvant treatment chemotherapy with carboplatin, etoposide, and radiotherapy for
positive tumor resection margins. Conclusions. Given the paucity of the cases of
MANEC, continuous reporting of these cases when identified should be encouraged
to aid oncologists in understanding the disease and help establish standardized
management.
PMID- 24348575
TI - Primary Cutaneous Vasculitis Masquerading as Drug Induced following Aspirin
Desensitization.
AB - Aspirin-exacerbated respiratory disease (AERD) is a well-known clinical
condition. Aspirin desensitization followed by daily aspirin therapy is the
treatment of choice. We report a challenging case of primary cutaneous vasculitis
following aspirin desensitization in a patient with AERD. The vasculitis was
likely suppressed with higher dose systemic steroid use to control asthma.
Aspirin desensitization led to improved asthma control and steroid reduction,
which led to manifestation of prior suppressed cutaneous vasculitis. In our case,
there was no evidence of systemic involvement and the patient had a favorable
outcome with appropriate therapy.
PMID- 24348576
TI - Caesarean delivery complicated by unintentional subdural block and conversion
disorder.
AB - Combined spinal epidural (CSE) can provide excellent labor analgesia. Subdural
block is also a potential but rare complication of attempted epidural placement
during a CSE procedure, which may present as a block that is usually patchy in
nature, with a component of sensory and/or motor deficit and a variable duration
of action. In addition, a conversion disorder or a functional neurological
disorder has been described with epidural and spinal anesthesia in obstetric
patients. In this clinical report, we describe a 33-year-old G4P3 at 40 weeks
gestation that received an unintentional subdural block as part of her labor
analgesia and after an uneventful caesarean delivery presented with a conversion
disorder. The rarity of the association between a subdural block and a conversion
disorder complicated by the fact that the neurological deficit produced by the
subdural block and that produced by a conversion disorder are similar in
distribution made the clinical presentation and diagnosis a challenge for the
obstetric anesthesia team. A functional neurological disorder of this nature
complicating a subdural block in an obstetric anesthesia clinical practice has
not been described so far.
PMID- 24348577
TI - Tenon's Cyst Presenting as a Long-Term Complication following Incision Cataract
Surgery.
AB - Context. Tenon's cyst or conjunctival cyst formation is not uncommon late
complication of traditional extracapsular cataract surgery; however, few reports
are available in the literature. Aims. Large cystic swellings were clinically
diagnosed as filtering blebs at the cataract incision site in two patients. The
purpose of the case presentation is to discuss the factors leading to cyst
formation, visual loss and cyst recurrence after its excision. Patients and
Methods. Case 1. Sixty-one-year-old male patient presented with a bleb at
superior limbal region in the right eye, two years after cataract surgery. Case
2. A giant bleb was found at the same region in the right eye of a 65-year-old
male patient, eight years after cataract surgery. Results. Complete excision of
the cyst was performed with conjunctival autograft in the first patient and
followed up for two years. No recurrence of the cyst was observed. Internal wound
gaping was seen on gonioscopy in the second patient. Conclusions. Unstable
scleral tunnel could explain bleb formation in both the patients. Complete bleb
excision with conjunctival auto-graft resulted in closure of the defect with no
bleb recurrence during two-year follow-up. Over-filtration causing hypotonic
maculopathy was the reason for decreased vision in the second case.
PMID- 24348578
TI - Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic
Phenotype.
AB - Morquio A syndrome (Mucopolysaccharidosis type IVA) (MPS IVA) is a rare inherited
metabolic disorder characterized by the defective degradation of keratan sulfate
and chondroitin-6-sulfate. Classically, MPS IVA patients present with severe
multisystemic involvement and have a short life expectancy. Attenuated forms with
clinical features limited to minor skeletal abnormalities and short stature have
also been described, sometimes associated to an early-onset osteoporotic
phenotype. No treatment with allogenic bone marrow transplantation or gene
therapy is currently available for Morquio A syndrome, and enzyme replacement
therapy is under evaluation. We report a case of MPS IVA, who manifested tardily
attenuated phenotype and significant bone mass reduction, which was treated with
a bisphosphonate (BPN), resulting in an improvement of X-ray skeletal aspects and
functional bone performance. We suggest that the use of bisphosphonates may be an
interesting supportive therapeutic option for Morquio A patients with
osteoporotic phenotype, but further studies involving more patients are necessary
to confirm our findings.
PMID- 24348579
TI - Dialysis and pregnancy in end stage kidney disease associated with lupus
nephritis.
AB - Female patients with systemic lupus erythematosus are often of childbearing age
at diagnosis, and though fertility in these patients is similar to the general
population, successful pregnancy remains a rare occurrence. This incidence is,
however, increasing and the management of these high risk pregnancies is often
further complicated by the patient's need for dialysis as a result of lupus
nephritis (LN). We share our experience in managing two LN patients with
successful pregnancies, one on automated peritoneal dialysis and the other on
haemodialysis, as well as a review of cases in the literature.
PMID- 24348580
TI - Differentiation of dental pulp stem cells into neuron-like cells in serum-free
medium.
AB - Dental pulp tissue contains dental pulp stem cells (DPSCs). Dental pulp cells
(also known as dental pulp-derived mesenchymal stem cells) are capable of
differentiating into multilineage cells including neuron-like cells. The aim of
this study was to examine the capability of DPSCs to differentiate into neuron
like cells without using any reagents or growth factors. DPSCs were isolated from
teeth extracted from 6- to 8-week-old mice and maintained in complete medium. The
cells from the fourth passage were induced to differentiate by culturing in
medium without serum or growth factors. RT-PCR molecular analysis showed
characteristics of Cd146(+) , Cd166(+) , and Cd31(-) in DPSCs, indicating that
these cells are mesenchymal stem cells rather than hematopoietic stem cells.
After 5 days of neuronal differentiation, the cells showed neuron-like
morphological changes and expressed MAP2 protein. The activation of Nestin was
observed at low level prior to differentiation and increased after 5 days of
culture in differentiation medium, whereas Tub3 was activated only after 5 days
of neuronal differentiation. The proliferation of the differentiated cells
decreased in comparison to that of the control cells. Dental pulp stem cells are
induced to differentiate into neuron-like cells when cultured in serum- and
growth factor-free medium.
PMID- 24348581
TI - Adaptive behavior in young children with neurofibromatosis type 1.
AB - Neurofibromatosis-1 is the most common single gene disorder affecting 1 in 3000.
In children, it is associated not only with physical features but also with
attention and learning problems. Research has identified a downward shift in
intellectual functioning as well, but to date, there are no published studies
about the everyday adaptive behavior of children with NF1. In this study,
parental reports of adaptive behavior of 61 children with NF1 ages 3 through 8
were compared to an unaffected contrast group (n = 55) that comprised siblings
and community members. Significant group differences in adaptive skills were
evident and were largely related to group differences in intellectual
functioning. In a subsample of children with average-range intellectual
functioning, group differences in parent-reported motor skills were apparent even
after controlling statistically for group differences in intellectual
functioning. The implications of the findings for the care of children with NF1
are discussed.
PMID- 24348582
TI - The attitudes and intention to participate in hemoglobinopathy carrier screening
in The Netherlands among individuals from Turkish, Moroccan, and Surinamese
descent.
AB - OBJECTIVE: To explore factors that influence intention to participate in
hemoglobinopathy (HbP) carrier screening under Dutch subjects at risk, since HbP
became more common in The Netherlands. METHOD: Structured interviews with 301
subjects from Turkish, Moroccan, or Surinamese ethnicity. RESULTS: Half of the
participants were familiar with HbP, 27% with carrier screening. Only 55%
correctly answered basic knowledge items. After balanced information, 83% percent
of subjects express intention to participate in HbP carrier screening. Intention
to participate was correlated with (1) anticipated negative feelings, (2) valuing
a physician's advice, and (3) beliefs on significance of carrier screening. Risk
perception was a significant determinant, while respondents were unaware of HbP
as endemic in their country of birth. Respondents preferred screening before
pregnancy and at cost < 50?. CONCLUSION: These findings show the importance of
informing those at risk by tailored health education. We propose easy access at
no costs for those willing to participate in HbP carrier screening.
PMID- 24348583
TI - Leaf area controls on energy partitioning of a temperate mountain grassland.
AB - Using a six year data set of eddy covariance flux measurements of sensible and
latent heat, soil heat flux, net radiation, above-ground phytomass and
meteorological driving forces energy partitioning was investigated at a temperate
mountain grassland managed as a hay meadow in the Stubai Valley (Austria). The
main findings of the study were: (i) Energy partitioning was dominated by latent
heat, followed by sensible heat and the soil heat flux; (ii) When compared to
standard environmental forcings, the amount of green plant matter, which due to
three cuts varied considerably during the vegetation period, explained similar,
and partially larger, fractions of the variability in energy partitioning; (iii)
There were little, if any, indications of water stress effects on energy
partitioning, despite reductions in soil water availability in combination with
high evaporative demand, e.g. during the summer drought of 2003.
PMID- 24348585
TI - Role of insulin in the type 2 diabetes therapy: past, present and future.
AB - CONTEXT: Since 2006 a relevant number of therapeutical algorithms for the
management of type 2 diabetes have been proposed, generating a lively debate in
the scientific community, particularly on the ideal timing for introduction of
insulin therapy and on which drug should be preferred as add-on therapy in
patients failing to metformin. At the moment, there is no real consensus. The aim
of the present review is to summarize established knowledge and areas for debate
with respect to insulin therapy in type 2 diabetes. EVIDENCE ACQUISITION: In type
2 diabetic patients, insulin represents a therapy with a long and well
established history, but, considering the modern insulin therapy, several points
must be carefully examined. The role played by the introduction of insulin
analogues, the choice of insulin regimens, the ongoing debate on insulin and
cancer, the cardiovascular effects of insulin, the role of insulin on beta-cell
protection and the actual clinical perspective in the treatment of the disease.
Nevertheless, still many exciting expectations exist: the new insulin analogues,
the technological options, the inhaled and oral insulin and the issue of
transplantation. CONCLUSIONS: Although insulin is the more potent hypoglicemic
agent, the availability of a wider spectrum of therapeutic agents, many of which
are better tolerated than insulin, has reduced the field of application for
insulin treatment; presently, insulin is used only in those who cannot maintain
an adequate glycemic control with other drugs. Furthermore, a lively research
activity is currently ongoing, in order to make insulin therapy even safer and
simpler for patients.
PMID- 24348584
TI - The role of estrogen in the treatment of men with schizophrenia.
AB - Schizophrenia is a debilitating and pervasive mental illness with devastating
effects on many aspects of psychological, cognitive and social wellbeing.
Epidemiological and life-cycle data point to significant differences in the
incidence and course of schizophrenia between men and women, suggesting that
estrogen plays a "protective" role . Adjunctive estrogen therapy has been shown
to be effective in enhancing the treatment of schizophrenia in women. In men,
consideration of estrogen therapy has been impacted by concerns of feminisation,
however, clinical trials using estrogen to treat prostate cancer, bone density
loss and even aggression in men with dementia or traumatic brain injury, show
estrogen to be a safe and effective therapy. Findings do, however, suggest that
further exploration of a therapeutic role for adjunctive estradiol treatment in
men with schizophrenia is warranted. The development of the new estrogen
compounds - Selective Estrogen Receptor Modulators (SERMs) which do not cause
feminisation - opens up the possibility of using a different type of estrogen for
a longer period of time at higher doses. Estrogen could therefore prove to be an
important component in the treatment of psychotic symptoms in men with
schizophrenia. This review explains the scientific rationale behind the estrogen
hypothesis and how it can be clinically utilised to address concerns unique to
the care of men with schizophrenia.
PMID- 24348586
TI - The effect of community-based education for lifestyle intervention on the
prevalence of metabolic syndrome and its components: tehran lipid and glucose
study.
AB - BACKGROUND: It has been shown that life style modification may decrease the
prevalence of metabolic syndrome, but this intervention has not been reported in
community setting. OBJECTIVES: Effect of lifestyle modification on prevalence of
metabolic syndrome and its components were assessed in an urban population.
MATERIALS AND METHODS: In 6870 participants of Tehran Lipid and Glucose Study
aged 20-74 years, the prevalence of metabolic syndrome and its components were
measured before and after a 3.6 years interval. Lifestyle intervention was
employed at a community level including 2961 individuals and also 3909 subjects
which were recruited as controls. Logistic regression analysis was adjusted for
age, sex and medications. RESULTS: After 3.6 years, the rise in the prevalence of
metabolic syndrome was less prominent in intervention than control group (P <
0.002 for increase of metabolic syndrome prevalence between groups), with an OR
of 0.84 (confidence interval 0.75-0.95). After intervention the prevalence of
abdominal obesity, elevated fasting glucose levels, elevated triglyceride and low
HDL cholesterol were more prominent in control group, as compared to intervention
group. CONCLUSIONS: Community based lifestyle modifications in Tehranian adults
delayed rise in the prevalence of metabolic syndrome and some of its components.
PMID- 24348587
TI - Expression and Localization of Neuregulin-1 (Nrg1) and ErbB2/ErbB4 Receptors in
Main Endocrine Organs of the Rhesus Monkey.
AB - BACKGROUND: Although Neuregulin-1 (Nrg1)and its receptors have been indicated at
the mRNA level in partial human endocrine organs and its functional roles have
been evaluated in vitro, their morphological distribution in higher animals are
not fully studied. The present research focused on expression of Nrg1 and its
main receptors ErbB2 and ErbB4 in main endocrine organs of the rhesus monkey.
MATERIALS AND METHODS: The morphological expression of Nrg1 and its receptors
ErbB2 and ErbB4 as well as their potential co-localization were determined by
double immunofluorescence in the pituitary, thyroid, parathyroid, pancreas and
adrenal gland sample tissues. The expression level of Nrg1 on each sample was
indexed by the fold of integrative fluorescence intensity (IFI) relative to that
of one cortical tissue. RESULTS: Differential expression of Nrg1 and their
cognate receptors ErbB2 and ErbB4 were found selectively expressed in endocrine
organs we tested, with higher expression levels detected in the adrenal gland
(AG) and pancreas. Co-localization of Nrg1 with either ErbB2 or ErbB4 was
detected in AG, thyroid and parathyroid gland, and Nrg1 was only co-localized
with ErbB4 in the islet cells of the pancreas. In the pituitary, adjacent
localization of Nrg1 positive cells with ErbB4 positive cells were observed.
CONCLUSIONS: This investigation morphologically profiles the differential
expression of Nrg1 and its receptors ErbB2 and ErbB4 in the main endocrine organ
structures, suggesting an autocrine or paracrine-directed Nrg1-ErbB signaling
pathway in some of these structures.
PMID- 24348588
TI - Effect of ethnicity, dietary intake and physical activity on plasma adiponectin
concentrations among malaysian patients with type 2 diabetes mellitus.
AB - BACKGROUND: The Malaysian Health and morbidity Survey (2006) reported the highest
prevalence of type 2 diabetes mellitus (T2DM) among the Indian population
compared to the Malay and Chinese populations. Many studies have supported the
important role of adiponectin in insulin-sensitizing, which is associated with
T2DM. These studies have raised a research question whether the variation in
prevalence is related to the adiponectin concentrations or the lifestyle factors.
OBJECTIVES: The purpose of this study is to determine whether the adiponectin
concentrations differ between the Malay, Chinese and the Indian populations with
T2DM. It is to investigate the association of adiponectin concentrations with
ethnicity, dietary intake and physical activity too. MATERIALS AND METHODS: In
this cross-sectional study, a total of 210 T2DM patients with mean (SD) age of
56.73 (10.23) years were recruited from Penang, Malaysia. Data on demographic
background, medical history, anthropometry (weight, height, visceral fat,
percentage of body fat and waist circumference), dietary intake (3 days 24 hours
diet recall) and physical activity (International Physical Activity
Questionnaire) were obtained accordingly. Plasma adiponectin and routine
laboratory tests (fasting blood sugar, HbA1c, total cholesterol, LDL, HDL and
triglyceride) were performed according to standard procedure. RESULTS: After
adjustment for physical activity and dietary intakes, the Indian population had
significantly lower adiponectin concentrations (P = 0.003) when compared with the
Malay and the Chinese populations, The Indian population also had significantly
higher value of HbA1c (P = 0.017) and significantly lower HDL (P = 0.013). Plasma
adiponectin concentrations was significantly associated with ethnicity (P =
0.011), dietary carbohydrate (P = 0.003) and physical activity total MET score (P
= 0.026), after medical history, age, sex, total cholesterol and visceral fat
adjusted. However, dietary carbohydrate and physical activity did not show
significantly difference among the various ethnic groups. CONCLUSIONS: In
conclusion, lower concentration of adiponectin in the Indian population when
compared with the Malay and the Chinese populations is not associated with
lifestyle factors. The possibility of adiponectin gene polymorphism should be
discussed further.
PMID- 24348589
TI - Effects of nutrition education on levels of nutritional awareness of pregnant
women in Western iran.
AB - BACKGROUND: Maternal nutritional health, before and during pregnancy, influences
the health status of herself and her developing fetus. Pregnancy is an important
condition for improving nutritional knowledge. OBJECTIVES: The present study
aimed at determining effects of nutrition education on levels of nutritional
awareness of a representative group of pregnant women in Western Iran. PATIENTS
AND METHODS: A quasi-experimental intervention was undertaken on a random sample
of pregnant women (n = 100) attending urban health centers in Ilam city (western
Iran) during the year 2011 for prenatal care. A nutritional education program
containing two to four lessons was undertaken for small groups of between six to
ten women. Nutritional knowledge was assessed before intervention (pretest) and
followed by two posttests within three weeks interval. RESULTS: The awareness
level of pregnant women about healthy nutrition was significantly increased from
3% before intervention to 31% after the nutritional education intervention (P <
0.001). This significant difference was independent from maternal characteristics
of age and levels of literacy and in obese mothers in particular. CONCLUSIONS: A
nutritional education intervention will have a positive effect on nutritional
awareness of pregnant women.
PMID- 24348590
TI - Is hypothyroidism and hypogonadism an issue after aneurysmal subarachnoid
hemorrhage-an institutional experience?
AB - BACKGROUND: The incidence of hypopituitarism in aneurysmal subarachnoid
hemorrhage ranges from 0% to 45%. Also the screening for hypopituitarism in
survivors of aneurysmal SAH is not a routine. This has led to a controversy in
the management of such patients. OBJECTIVES: The aim of the study was to evaluate
the endocrine profile of our patients who had presented with aneurysmal SAH.
PATIENTS AND METHODS: This was a prospective study conducted over a period of
three years in patients of aneurysmal subarachnoid hemorrhage. The serum samples
for levels of free T4, free T3, TSH, prolactin, FSH, LH and testosterone were
analyzed at the time of admission and at a follow-up period between 9-12 months.
Patients with known endocrine abnormalities, liver or kidney disease and patients
with hemodynamic abnormalities were excluded from the study. Abnormalities in
levels were noted and a comparative analysis of the hormone levels between the 2
time periods was done. A total of 73 patients were enrolled in the study.
RESULTS: Serum prolactin was raised in 17.80% (13/73) and FSH, LH and
testosterone levels were reduced in 12.32% (9/73) of patients in the acute phase
at admission. After 9 months follow-up, serum prolactin normalized in all except
one patient and in all the males, testosterone level increased significantly. Two
patients (3%) developed central hypothyroidism on follow-up. CONCLUSIONS: Chronic
hypothyroidism and hypogonadism is not an issue in aneurysmal SAH patients.
PMID- 24348591
TI - Liraglutide Improves the Survival of INS-1 Cells by Promoting Macroautophagy.
AB - BACKGROUND: Type 2 diabetes mellitus (T2D) is a metabolic disease characterized
by dysfunction of pancreatic beta cell and insulin resistance. Liraglutide, which
has many special anti-diabetes biological effects, is found to inhibit beta cell
death and ameliorate endoplasmic reticulum stress (ERs) induced by free fatty
acid (FFA). Macroautophagy (hereafter referred to as autophagy) altered by FFA is
also associated with the dysfunction or death of pancreatic beta cells.
OBJECTIVES: We aim at proving that Liraglutide improves the survival of INS-1
cells by promoting autophagy. MATERIALS AND METHODS: Cell survival was assessed
by CCK8 assay. The percentage of apoptotic cells was determined by flow
cytometric assay after Annexin V-FITC/PI staining. Expression of LC3 was detected
by western blotting. MDC staining and transmission electron microscopy (TEM) were
used in the measurement of autophagy. RESULTS: Apoptosis induced by PA in INS-1
cells was significantly resolved after Liraglutide treatment. Simultaneously,
autophagy was enhanced with the treatment of PA and Liraglutide. CONCLUSIONS:
Liraglutide appears to protect INS-1 cells from apoptosis FFA-induced by
promoting autophagy. CONCLUSIONS: These findings provide a novel role for GLP-1
analogue in preventing or treating with T2D.
PMID- 24348593
TI - Leksell Gamma Knife : An Effective Non Invasive Treatment for Rare Case of
Nelson's Syndrome.
AB - Nelson's syndrome nowadays a rare entity results from an adrenocorticotropin
(ACTH)-secreting pituitary adenoma in patients with refractory Cushing's disease
after a therapeutic bilateral adrenal gland removal. We report a case of 25 year
old female with cushing's disease who was initially managed with medical
treatment, but in view of severe persistent hyper cortisol state was subjected to
bilateral adrenalectomy following which she developed Nelson's syndrome after a
gap of six years, which was difficult to diagnose because of limited
investigations available. Patient was managed with stereotactic radiosurgery
(gamma knife surgery).
PMID- 24348592
TI - Coexistent Papillary Carcinoma of Thyroid and Hashimoto's Thyroiditis - Diagnosis
on Fine Needle Aspiration Cytology.
AB - Hashimoto's thyroiditis is associated with an increased risk of developing
papillary carcinoma of thyroid. We hereby report a case of Hashimoto's
thyroiditis with papillary carcinoma in a 45-year-old ear old female diagnosed on
fine needle aspiration cytology (FNAC) which was later confirmed on
histopathological examination .Such an occurrence, when both lesions are picked
up on FNAC in a patient with no palpable thyroid nodule is rare. The case is
presented here for its rarity.
PMID- 24348595
TI - Demographic factors influencing consensus opinion on the recall for women
screened by mobile mammography unit in taiwan.
AB - BACKGROUND: The incidence of breast cancer has had a four-fold increase from 1980
to 2005 in Taiwan. Limited data have been available on mobile breast screening in
the Taiwanese population since 2009. OBJECTIVES: This study aims at investigating
the factors influencing consensus opinion on the recall for mobile breast
screening in Taiwan. PATIENTS AND METHODS: The factors were categorized by
individual health background, socioeconomic status and knowledge about breast
screening. There were 502 questionnaires collected from Taiwanese women examined
on mobile mammography screening vehicle. Data were then analyzed by SPSS 12 via
analysis of variance (ANOVA), F-test, t-test or chi-square test. RESULTS: Strong
participation was associated with a younger age, higher educational level, higher
incomes, previous history of cancer, previous family history of cancer, one or
two prior mammographies, more correct recognitions of mammography, recall rate,
and breast cancer risk. If the false-positive result occurred, 83.9%, 81.9% and
77.3% of the women agreed or strongly agreed to participate in noninvasive and
invasive testing and screening mammography, respectively. CONCLUSION: The policy
makers should notify the importance of demographic factors affecting further
examination for early detection of breast cancer in Taiwan.
PMID- 24348594
TI - Comparing ovarian radiation doses in flat-panel and conventional angiography
during uterine artery embolization: a randomized clinical trial.
AB - BACKGROUND: Uterine artery embolization (UAE) is a minimally invasive procedure
performed under fluoroscopy for the treatment of uterine fibroids and accompanied
by radiation exposure. OBJECTIVES: To compare ovarian radiation doses during
uterine artery embolization (UAE) in patients using conventional digital
subtraction angiography (DSA) with those using digital flat-panel technology.
PATIENTS AND METHODS: Thirty women who were candidates for UAE were randomly
enrolled for one of the two angiographic systems. Ovarian doses were calculated
according to in-vitro phantom study results using entrance and exit doses and
were compared between the two groups. RESULTS: The mean right entrance dose was
1586+/-1221 mGy in the conventional and 522.3+/-400.1 mGy in the flat panel group
(P=0.005). These figures were 1470+/-1170 mGy and 456+/-396 mGy, respectively for
the left side (P=0.006). The mean right exit dose was 18.8+/-12.3 for the
conventional and 9.4+/-6.4 mGy for the flat panel group (P=0.013). These figures
were 16.7+/-11.3 and 10.2+/-7.2 mGy, respectively for the left side (P=0.06). The
mean right ovarian dose was 139.9+/-92 in the conventional and 23.6+/-16.2 mGy in
the flat panel group (P<0.0001). These figures were 101.7+/-77.6 and 24.6+/-16.9
mGy, respectively for the left side (P=0.002). CONCLUSION: Flat panel system can
significantly reduce the ovarian radiation dose during UAE compared with
conventional DSA.
PMID- 24348596
TI - Interobserver and Intraobserver Agreement of Sonographic BIRADS Lexicon in the
Assessment of Breast Masses.
AB - BACKGROUND: BI-RADS was first developed in 1993 for mammography and in 2003 it
was redesigned for ultrasonography (US). If the observer agreement is high, the
method used in the classification of lesion would be reproducible. OBJECTIVES:
The aim of this study is to evaluate the inter- and intraobserver agreement of
sonographic BI-RADS lexicon in the categorization and feature characterization of
nonpalpable breast lesions. PATIENTS AND METHODS: We included 223 patients with
245 nonpalpable breast lesions who underwent ultrasound-guided wire needle
localization. Two radiologists retrospectively described each lesion using
sonographic BI-RADS descriptors and final assessment. The observers were blinded
to mammographic images, medical history and pathologic results. Inter- and
intraobserver agreement was assessed using Kappa (kappa) agreement coefficient.
RESULTS: The interobserver agreement for sonographic descriptors changed between
fair and substantial. The highest agreement was detected for mass orientation
(kappa=0.66). The lowest agreement was found in the margin (kappa=0.33). The
interobserver agreement for BI-RADS final category was found as fair
(kappa=0.35). The intraobserver agreement for sonographic descriptors changed
between substantial and almost perfect. The intraobserver agreement of BI-RADS
result category was found as substantial for observer 1 (kappa=0.64) and
excellent for observer 2 (kappa=0.83). CONCLUSION: Our results demonstrated that
each observer was self-consistent in interpreting US BI-RADS classification,
while interobserver agreement was relatively poor. Although it has been ten years
since the description of sonographic BI-RADS lexicon, further training and
periodic performance evaluations would probably help to achieve better agreement
among radiologists.
PMID- 24348597
TI - Magnetic resonance spectroscopic findings of chronic lesions in two subtypes of
multiple sclerosis: primary progressive versus relapsing remitting.
AB - BACKGROUND: Multiple sclerosis (MS) is a highly prevalent cause of neurological
disability and has different clinical subtypes with potentially different
underlying pathologies. Differentiation of primary progressive multiple sclerosis
(PPMS) from relapsing remitting multiple sclerosis (RRMS) could be difficult
especially in its early phases. OBJECTIVES: We compared brain metabolite
concentrations and ratios in patients with PPMS and RRMS by magnetic resonance
spectroscopic imaging (MRSI). PATIENTS AND METHODS: Thirty patients with definite
MS (15 with RRMS and 15 with PPMS) underwent MRSI and their non-enhancing lesion
metabolites were measured. N-acetyl aspartate (NAA), Creatine (Cr), Choline
(Cho), NAA/Cr and NAA/Cho were measured and compared between the two MS subtypes.
RESULTS: When the two MS groups were compared together, we found that Cr was
significantly increased (P value=0.008) and NAA/Cr was significantly decreased (P
value=0.03) in non-enhancing lesions in PPMS compared with RRMS. There was no
significant difference in NAA, Cho or NAA/Cho between the two MS subtypes.
CONCLUSION: MRS is a potential way to differentiate PPMS and RRMS.
PMID- 24348598
TI - Endovascular stent placement of juxtaanastomotic stenosis in native arteriovenous
fistula after unsuccessful balloon angioplasty.
AB - BACKGROUND: In hemodialysis patients, the most common problem in arteriovenous
fistulas, as the best functional vascular access, is the juxtaanastomotic located
lesions. Percutaneous transluminal angioplasty is accepted as the treatment
method for juxtanastomotic lesions. OBJECTIVES: To assess juxtaanastomotic stent
placement after insufficient balloon angioplasty in the treatment of autogenous
radiocephalic or brachiocephalic fistula dysfunction. PATIENTS AND METHODS:
Between July 2003 and June 2010, 20 hemodialysis patients with autogenous
radiocephalic or brachiocephalic fistula dysfunction underwent stent placement
for the lesion located at the juxtaanastomotic region. Indications for stent
placement were insufficient balloon dilatation, early recurring stenosis, chronic
organizing thrombus and vessel rupture. The Kaplan-Meier method was used to
calculate the stent patency rates. All patients who had fistula dysfunction
(thrombosis of hemodialysis access, difficult access cannulation, extremity pain
due to thrombosis or decreased arterial access blood flow) were evaluated by
color Doppler ultrasound. The stenoses were initially dilated with standard
noncompliant balloons (3 to 10-mm in diameter). Dilatation was followed by high
pressure (Blue Max, Boston Scientific) or cutting balloons (Boston Scientific),
if the standard balloon failed to dilate the stenotic segment. RESULTS: Twenty
one stents were applied. The anatomical and clinical success rate was 100%.
Seventeen additional interventions were done for 11 (55%) patients due to stent
thrombosis or stenosis during follow-up. Our 1- and 2-year secondary patency
rates were 76.2% and 65.5%, respectively and were comparable to those after
balloon angioplasty and surgical shunt revision. CONCLUSION: Metallic stent
placement is a safe and effective procedure for salvage of native hemodialysis
fistula after unsuccessful balloon angioplasty.
PMID- 24348599
TI - Identification of Nasal Bone Fractures on Conventional Radiography and Facial CT:
Comparison of the Diagnostic Accuracy in Different Imaging Modalities and
Analysis of Interobserver Reliability.
AB - BACKGROUND: There has been no study to compare the diagnostic accuracy of an
experienced radiologist with a trainee in nasal bone fracture. OBJECTIVES: To
compare the diagnostic accuracy between conventional radiography and computed
tomography (CT) for the identification of nasal bone fractures and to evaluate
the interobserver reliability between a staff radiologist and a trainee. PATIENTS
AND METHODS: A total of 108 patients who underwent conventional radiography and
CT after acute nasal trauma were included in this retrospective study. Two
readers, a staff radiologist and a second-year resident, independently assessed
the results of the imaging studies. RESULTS: Of the 108 patients, the presence of
a nasal bone fracture was confirmed in 88 (81.5%) patients. The number of non
depressed fractures was higher than the number of depressed fractures. In nine
(10.2%) patients, nasal bone fractures were only identified on conventional
radiography, including three depressed and six non-depressed fractures. CT was
more accurate as compared to conventional radiography for the identification of
nasal bone fractures as determined by both readers (P <0.05), all diagnostic
indices of an experienced radiologist were similar to or higher than those of a
trainee, and kappa statistics showed moderate agreement between the two
diagnostic tools for both readers. There was no statistical difference in the
assessment of interobserver reliability for both imaging modalities in the
identification of nasal bone fractures. CONCLUSION: For the identification of
nasal bone fractures, CT was significantly superior to conventional radiography.
Although a staff radiologist showed better values in the identification of nasal
bone fracture and differentiation between depressed and non-depressed fractures
than a trainee, there was no statistically significant difference in the
interpretation of conventional radiography and CT between a radiologist and a
trainee.
PMID- 24348600
TI - Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the
Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report.
AB - Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for
only 0.8% of all tonsillar tumors, with only 100 cases reported in the English
language literature. Various malignant lung carcinomas may metastasize to the
tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma
have been reported. A 67-year-old female underwent a right tonsillectomy because
of a sore throat and an enlarged right tonsil. The postoperative pathology showed
right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose
(FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated
metabolic activity in the lower lobe of the right lung. In addition,
hypermetabolic foci were noted in the lymph nodes of the right neck and
mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient
received chemotherapy and died of multiple distant metastases after 6 months.
This is the first report using PET/CT to evaluate tonsillar metastasis from lung
SCNC.
PMID- 24348601
TI - A rare case of rib osteoblastoma: imaging features and review of literature.
AB - Osteoblastoma is a rare benign, but locally aggressive bone tumor with rare
malignant transformation. It mostly affects the vertebral column and long bones.
Radiographically, it is seen as an expansile, oval, sclerotic or lytic mass-like
lesion with well-defined borders, although sometimes it may mimic a malignant
tumor such as osteogenic sarcoma by its irregular borders. Herein, we report a
case of osteoblastoma in a 22 year-old man with a long history of back and neck
pain accompanied with neck stiffness. On the routine chest X-ray, the salient
lesion appeared as an expansile, oval, sclerotic mass with well-defined borders
and speckled calcification without any internal lucency and periosteal reaction,
involving the posterolateral aspect of the first left thoracic rib, a rare
anatomical site. Despite the unusual location, osteoblastoma should be considered
in the differential diagnosis of a solitary rib lesion.
PMID- 24348602
TI - Acute appendicitis presenting as unusual left upper quadrant pain.
AB - Appendicitis is the most common abdominal disease that requires surgery in the
emergency ward. It usually presents as right lower quadrant pain, but may rarely
present as left upper quadrant (LUQ) pain due to congenital anatomical
abnormalities of the intestine. We report a patient who complained of persistent
LUQ abdominal pain and was finally diagnosed by computed tomography (CT) as
congenital intestinal malrotation complicated with acute appendicitis. It is
important to include acute appendicitis in the differential diagnosis of patients
who complain of LUQ abdominal pain. Abdominal CT can provide significant
information that is useful in preoperative diagnosis and determination of proper
treatment.
PMID- 24348603
TI - Urography and CT Features of Primary Small Cell Carcinoma of the Ureter: A Case
Report.
AB - Primary small cell carcinoma of the ureter is an extremely rare disease, only
several cases have been reported worldwide so far. We report a 70-year-old woman
who was examined with intravenous urography and abdominal computed tomography and
was diagnosed as small cell carcinoma confirmed by pathology. We describe and
discuss the urography and computed tomography findings of this case.
PMID- 24348604
TI - Paraspinal and presacral extramedullary hematopoiesis: a rare manifestation of
polycythemia vera.
AB - Extramedullary hematopoiesis is characterized by the presence of hematopoietic
tissue outside the bone marrow. Extrathoracic extramedullary hematopoiesis is a
rare and usually asymptomatic condition. We report a case of a 38-year-old female
with paraspinal and presacral extramedullary hematopoiesis with polycythemia
vera. Clinical and laboratory evaluation, along with radiological and
histopathological findings are described. The diagnosis of the disease was
confirmed by CT-guided biopsy. Review of literature is presented.
PMID- 24348605
TI - A case of neonatal urosepsis with multifocal osteoarthritis: could
ultrasonography change the clinical course?
AB - An eleven-day boy neonate with a fetal anamnesis of grade 1 bilateral
hydronephrosis according to the grading of the Society for Fetal Urology (SFU),
came to our attention for an acute osteoarthritis secondary to urosepsis. In the
urological follow-up, a severe bilateral vesico-ureteral reflux (VUR) was
diagnosed. An early post-natal, reno-vesicle ultrasound evaluation could have
changed the clinical course of our patient.
PMID- 24348606
TI - Different MRI signs in predicting the treatment efficacy of epidural blood patch
in spontaneous intracranial hypotension: a case report.
AB - The current mainstay of treatment in spontaneous intracranial hypotension (SIH)
is an epidural blood patch (EBP). Although magnetic resonance imaging (MRI) has a
well-established role in the diagnosis of SIH, imaging features regarding the
treatment efficacy of EBP have rarely been discussed. We therefore sought to
investigate and compare the sequential brain MRI studies before and after EBP by
evaluating the changes of the following intracranial structures-the contour of
the transverse dural sinus (TDS), tension of the pituitary stalk (or the
infundibulum), and thickness of the dura mater. We found that the progressive
reversals of these structures are predictive of an effective EBP.
PMID- 24348607
TI - Well-differentiated intraosseous osteosarcoma in the sacrum: a case report.
AB - Hereby we report a case of well-differentiated intraosseous osteosarcoma in the
sacrum. A 32-year-old woman was admitted to our hospital with a low echo-level
mass in the pelvis searched by ultrasound in a routine physical examination.
Radiographically, the mass was misdiagnosed as a benign bony tumor originating
from the sacrum. The tumor was completely resected and pathological diagnosis was
intraosseous well-differentiated osteosarcoma. Twelve months after operation, the
patient was well and there was no evidence of recurrence and distal metastasis.
This is a peculiar case of well-differentiated osteosarcoma involving an unusual
site of the sacrum. The radiographic appearance and the differential diagnosis
are discussed. We consider that dense trabeculated-like bone within an
intraosseous solid mass might be suggestive of a well-differentiated osteosarcoma
that was valuable in guiding the treatment and prediction of its prognosis. Well
differentiated osteosarcoma, although malignant, may be mistaken for a benign
condition. Local excision has almost always been associated with recurrence. For
this case, the patient had a wide excision and had no recurrence and metastasis.
Therefore, it is very important to identify the radiological features and to
distinguish this tumor from benign lesions and high-grade osteosarcomas before
operation.
PMID- 24348608
TI - Assessing the oldness and capacity of radiography and ultrasound equipments in
tehran university of medical sciences.
AB - BACKGROUND: Maintenance of imaging equipment is a very important part of the
management of all medical imaging centers. OBJECTIVES: To assess the oldness and
capacity of radiography and ultrasound equipment in Tehran University of Medical
Sciences. MATERIALS AND METHODS: The study was performed in 16 hospitals, 4
faculties and three healthcare centers of Tehran University of Medical Sciences.
We evaluated all the X-ray equipment (including the simple plain and dental,
panorex, mammography, fluoroscopy and C-arm X-Ray devices) and also simple and
Doppler ultrasound machines in terms of the type and usage of the device,
production year, quantity of utilization, location, brand and current condition.
RESULTS: Among fixed X-ray systems, 15 were currently in use, two were junk, two
were damaged, and one was not utilized. The mean (SD) of the usage of these was
2151 (2230) cliche/month, and the mean (SD) of the oldness was 16.9 (13.6) years.
The oldness of radiography equipment in our study was more than 20 years in 16,
between 11 and 20 in 46, and less than 10 years in 76 devices. The mean (SD)
usage (patients/month) of simple and color Doppler devices were 234.1 (365.2) and
597.5 (505.3), respectively. The oldness of ultrasonography equipment in our
study was more than 11 years in 12 and less than 10 years in 55 devices. We found
that 22 (15.9%) of the radiography systems and two (3%) of the ultrasonography
systems had been used for more than 20 years. CONCLUSION: Radiology equipment in
Tehran University of Medical Sciences have potential capacity, but they need
repair, and better maintenance and management and application of standards for
the imaging system needs organized supervisory mechanisms.
PMID- 24348609
TI - Percutaneous liver biopsies guided with ultrasonography: a case series.
AB - BACKGROUND: Although liver biopsy is an easy procedure for hospitalized patients
and outpatients, some complications may occur. OBJECTIVES: To evaluate the
efficiency, complications, safety and clinicopathological utility of
ultrasonographic-guided percutaneous liver biopsy in diffuse liver disease.
PATIENTS AND METHODS: In our retrospective study, we evaluated ultrasound
assisted needle biopsies that were performed in outpatients from October 2006 to
July 2010. The liver biopsies were performed following one-night fasting using
the tru-cut biopsy gun (18-20 gauge) after marking the best seen and hypovascular
part of the liver, distant enough from the adjacent organs. RESULTS: A total of
1018 patients were referred to our radiology department. Most of the patients had
hepatitis B (60.6%). The biopsy specimens were recorded and sent to our pathology
department for histopathological examination. CONCLUSION: According to the
results of our series, percutaneous liver biopsy using the tru-cut biopsy gun
guided by ultrasonography can be performed safely. We resolve that routine
ultrasound of the puncture site is a quick, effective and safe procedure. The
complication rate is very low. The US-assisted percutaneous liver biopsy should
be used for all cases.
PMID- 24348610
TI - Association between obstetric conjugate diameter measured by transabdominal
ultrasonography during pregnancy and the type of delivery.
AB - BACKGROUND: Normal morphological features of the maternal pelvis are an important
prerequisite to vaginal delivery. OBJECTIVES: We aimed to evaluate the
association between obstetric conjugate diameter (OCD) measured by
ultrasonography and the type of delivery, vaginally (V) or by cesarean (C)
section. PATIENTS AND METHODS: Pelvimetry was performed in 200 primigravid women
for fetal cephalic presentation. The OCD was measured twice by transabdominal
ultrasonography during 25-30 weeks and 30-35 weeks of pregnancy. RESULTS: The
mean OCD of both sonographies in groups V and C was 125.51+/- 8.35 mm (105-144.5)
and 112.99 +/- 8.53 mm (96-134.5), respectively, which was significantly lower in
group C (P<0.001). The values of OCD between the first and second measurements
were not different significantly (P=0.065). C-section was indicated in 65 (32.5%)
mothers. The optimal cut-off point for the OCD in the prediction of vaginal
delivery was >= 119.75 mm, with a sensitivity and specificity of 80% and 78.5%,
respectively. CONCLUSION: The US measurement of OCD might be an accurate method
that almost always remains constant during late pregnancy; it is easy to measure
and might be confidentially employed for predicting C-section, but needs more
precise studies to be used widely.
PMID- 24348611
TI - Sella turcica-Its importance in orthodontics and craniofacial morphology.
AB - The sella turcica is a structure which can be readily seen on lateral
cephalometric radiographs and sella point is routinely traced for various
cephalometric analyses. The search was carried out using the following key words
(sella turcica, bridging of sella, size, shape of sella turcica) and with the
following search engine (Pubmed, Cochrane, Google scholar). The morphology is
very important for the cephalometric position of the reference point sella, not
only for evaluating craniofacial morphology, but also when growth changes and
orthodontic treatment results are to be evaluated. This makes it a good source of
additional diagnostic information related to pathology of the pituitary gland, or
to various syndromes that affect the craniofacial region. Clinicians should be
familiar with the normal radiographic anatomy and morphologic variability of this
area, in order to recognize and investigate deviations that may reflect
pathological situations, even before these become clinically apparent. During
embryological development, the sella turcica area is the key point for the
migration of the neural crest cells to the frontonasal and maxillary
developmental fields. The neural crest cells are involved in the formation and
development of sella turcica and teeth. The size of sella turcica ranges from 4
to 12 mm for the vertical and 5 to 16 mm for the anteroposterior dimension. There
are many classification systems regarding the shape of sella turcica. Majority of
the studies show that about 67% of the subjects had normal appearance and about
33% showed variations. The prevalence of sella turcica bridging is high in class
III malocclusions and dental anomalies.
PMID- 24348612
TI - Biochemical markers in oral submucous fibrosis: A review and update.
AB - Oral submucous fibrosis (OSMF) is a potentially malignant oral condition
effectively linked to the causative habit of chewing areca nut. Since its first
description in the 1950s, numerous epidemiological, biochemical, histological,
and genetic studies have been reported. While most studies point out to the cause
and effect of areca nut, co-additive factors are also implicated in the
progression and malignant transformation of this condition. Biochemical
investigations have concentrated on outlining such changes in the blood, serum or
tissues of these patients and have given insights on the possible pathogenesis of
OSMF. This article attempts to compile details of biochemical investigations in
OSMF and summarize and infer on the findings.
PMID- 24348614
TI - Clinico-pathological study of odontomas in 19 Libyan patients.
AB - BACKGROUND: Odontomas are among the most common benign odontogenic tumors, which
are mostly discovered in the first and second decades of life with no clear sex
predilection. MATERIALS AND METHODS: The present retrospective study reviews the
clinical, radiological, and the histopathological characteristics of odontomas in
19 Libyan patients seen during the last 18 years in our department. RESULTS: Most
odontomas in our study were discovered when they obstruct a tooth from an
eruption at its normal eruption time although a few cases were noticed on routine
radiological examination of the region. Panoramic radiographs computed Tomography
Scan of the area and the histopathological examination are helpful to elicit the
diagnosis. Two cases in this series were found associating with dentigerous cyst
and in another two cases the odontomas were seen erupting intraorally.
CONCLUSION: Odontomas should be considered in the differential diagnosis of the
mixed radioopaque radiolucent lesions, especially if they found obstructing the
teeth from eruption.
PMID- 24348613
TI - Dental abscess: A microbiological review.
AB - Dental abscess is a frequently occurring infectious process known to the health
practice. The fate of the infection depends on the virulence of the bacteria,
host resistance factors, and regional anatomy. Serious consequences arising from
the spread of a dental abscess lead to significant morbidity and mortality. Acute
dental abscess is polymicrobial, comprising of strict anaerobes, such as
anaerobic cocci, Prevotella, Fusobacterium species, and facultative anaerobes,
such as viridans group streptococci and the Streptococcus anginosus group.
Numerous novel, uncultivable and fastidious organisms have been identified as
potential pathogens with the use of non-culture techniques. The majority of
localized dental abscesses respond to surgical treatment while the use of
antimicrobials is limited to severe spreading infections. There is a need for
good-quality clinical trials of sufficient size to identify the ideal treatment.
The microbiology of the acute dentoalveolar abscess and its treatment in the
light of improved culture and diagnostic methods are reviewed.
PMID- 24348615
TI - The effect of re-bonding using surface sealant or adhesive system on microleakage
of class V resin composite restorations.
AB - BACKGROUND: Microleakage is still one of the defects of resin composites that can
lead to treatment failure; and re-bonding technique is one of the effective ways
to reduce it. This study evaluated the effect of re-bonding with a surface
sealant or a dentin adhesive on microleakage in class V microhybrid, nanohybrid,
and packable composite restorations. MATERIALS AND METHODS: In this in vitro
study, class V cavities with occlusal margins in enamel and cervical margins in
dentin/cementum were prepared on the buccal and lingual surfaces of 54 extracted
premolars. The prepared teeth were randomly assigned to three groups (3 group's
Chi 18 teeth each), with each group being restored with microhybrid (Point 4);
nanohybrid (Herculite XRV Ultra), and packable (Packable Premise) resin
composite. Following finishing and polishing procedures, each group was randomly
subdivided in to three subgroups (n = 12). The margins of two groups were both
etched and re-bonded with surface sealant (Optiguard) or dentin adhesive (Opti
Bond Solo Plus) and control group received no treatment. Specimens were
thermocycled 1500 cycles, immersed in a methylene blue, sectioned, evaluated for
microleakage using a stereomicroscope at a x 20 and scored on a scale of 0-3.
Data were analyzed with Kruskal - Wallis, Mann - Whitney, and Wilcoxon tests
(alpha = 0.05). RESULTS: There were no significant differences among the three
resin composites tested, and also no significant differences among subgroups with
the same surface treatment. Only the microhybrid and packable composite
restorations sealed with Optiguard had significantly lower microleakage compared
to the control subgroups at the occlusal margin. There were no significant
differences between occlusal and cervical margins regarding the microleakage
scores when compared to the control subgroups of microhybrid and packable
composite restorations. CONCLUSION: The re-bonding technique could be considered
as an advisable procedure in order to minimize microleakage and its effect might
be material-dependent.
PMID- 24348616
TI - Lateral ridge split and immediate implant placement in moderately resorbed
alveolar ridges: How much is the added width?
AB - BACKGROUND: Lateral ridge split technique is a way to solve the problem of the
width in narrow ridges with adequate height. Simultaneous insertion of dental
implants will considerably reduce the edentulism time. MATERIALS AND METHODS:
Twenty-five patients who were managed with ridge splitting technique were
enrolled. Thirty-eight locations in both jaws with near equal distribution in
quadrants received 82 dental fixtures. Beta Tricalcium phosphate (Cerasorb((r)) )
was used as biomaterial to fill the intercortical space. Submerged implants were
used and 3 months later healing caps were placed. Direct bone measurements before
and after split were done with a Collis. Patients were clinically re-evaluated at
least 6 months after implant loading. All the data were analyzed by Statistical
Package for Social Sciences (SPSS) software version 11.5 (SPSS Inc, Chicago
Illinois, USA). Frequency of edentulous spaces and pre/post operative bone width
was analyzed. Paired t-test was used for statistical analysis. Difference was
considered significant if P value was less than 0.05. RESULTS: Mean value for
presplit width was 3.2 +/- 0.34 mm while post-split mean width was 5.57 +/- 0.49
mm. Mean gain in crest ridge after ridge splitting was 2 +/- 0.3 mm. Statistical
analysis showed significant differences in width before and after operation ((P >
0.05). All implants (n = 82) survived and were in full function at follow up (at
least 6 months after implant loading). CONCLUSION: Ridge splitting technique in
both jaws showed the predictable outcomes, if appropriate cases selected and
special attention paid to details; then the waiting time between surgery and
beginning of prosthodontic treatment can be reduced to 3 month.
PMID- 24348617
TI - The comparison of salivary level of estrogen and progesterone in 1(st) , 2(nd)
and 3(rd) trimester in pregnant women with and without geographic tongue.
AB - BACKGROUND: Geographic tongue (GT) was first reported as a wandering rash of the
tongue in 1831; however, its etiopathogenesis remains unclear. Increased
prevalence of GT has been documented in the pregnancy. The aim of this study was
to compare the level of salivary estrogen and progesterone in pregnant women with
and without GT. MATERIALS AND METHODS: This analytical-descriptive study
consisted of 26 pregnant women (13 with GT, 13 without GT) with an age range
between 18 years and 45 years. The estrogen and progesterone level was measured
during 1(st) , 2(nd) and 3(rd) trimester of pregnancy. Saliva sampling was
performed to determine the level of sex hormones. The samples were stored at -80
degrees C and determined by Eliza method. The results were analyzed by t-test and
repeated measure ANOVA (alpha = 0.05). RESULTS: The mean level of estrogen for
control and case group was 49.4and 52.33 in the 1(st) , 71.05 and 74.12 in the
2(nd) and 109.1 and 112.16 in the 3(rd) trimester respectively. The mean level of
progesterone was 0.72 and 0.72 in the 1(st) , 1.14 and 1.21 in the 2(nd) and 1.3
and 1.28 in the 3(rd) trimester of pregnancy for the control and case groups
respectively. Even though, there was no significant difference regarding the
level of sex hormones between case and control groups (P < 0.05), but the
difference between the level of these hormones during 3 trimesters of pregnancy
was significant in each group (P = 0.001). CONCLUSION: The level of sex hormones
is not the only etiologic factor of GT in pregnant women, but other factors such
as genetic potential, human leukocyte antigen marker and stress may aggravate the
incidence of this lesion.
PMID- 24348618
TI - Gingivitis and periodontitis as a risk factor for stroke: A case-control study in
the Iranian population.
AB - BACKGROUND: Periodontitis and gingivitis are one of the most infectious diseases
in human. Several studies have been carried out on dependence of periodontitis
and stroke. The aim of this study was to investigate the gingivitis and
periodontitis as a risk factor for stroke in Iranian population. MATERIALS AND
METHODS: A case-control study was conducted on 100 patients suffering from stroke
as case group, and 100 hospitalized patients as control group. The case group
included 42 males and 58 females, and in control group there were 44 males and 56
females. Using a University of North Carolina-15 manual probe, the clinical
attachment level, the distance between the cemento-enamel junction and the probed
base of the periodontal pocket, were recorded by gingival and periodontal
indexes. The data were analyzed by multiple logistic regressions, Chi-square
test, Fisher's test, t-test, Man Whitney, and SPSS11.5 software program. P > 0.05
was considered as significant. RESULTS: The case group included 42 males and 58
females, and in control group 44 males and 56 females were included. In this
investigation, the average of gingival index in men and women of case group was
1.22 +/- 0.55 and 1.31 +/- 0.55, respectively. This study showed that the average
of gingival index in case group was more than control group. Periodontal index in
both groups in men was more than women. The moderate and severe periodontitis in
case group were more than that of control group (P = 0.003, P = 0.001).
CONCLUSION: The result of this study shows that there is a significant relation
between stroke and periodontal index; however, there isn't any significant
relation between stroke and gingival index.
PMID- 24348619
TI - Comparison of the efficacy of two anesthetic techniques of mandibular primary
first molar: A randomized clinical trial.
AB - BACKGROUND: The most common technique to anesthetize mandibular primary teeth is
inferior alveolar (I.A) nerve block injection which induces a relatively
sustained anesthesia and in turn may potentially traumatize soft-tissues.
Therefore, the need of having an alternative technique of anesthesia with a
shorter term but the same efficacy is reasonable. The aim of this study was a
comparison of the efficacy of two anesthetic techniques of mandibular primary
first molar. MATERIALS AND METHODS: In this randomized crossover clinical trial,
40 children with ages ranged from 5 years to 8 years whose mandibular primary
first molars were eligible for pulpotomy, were selected and divided randomly into
two groups. The right and left mandibular first molars of group A were
anesthetized with infiltration and I. A nerve block techniques in the first and
second sessions respectively. The left and right mandibular first molars of group
B were anesthetized with I.A nerve block and infiltration techniques in the first
and second sessions respectively. The severity of pain were measured and recorded
according to sound-eye-motor scale by a certain person. Data was analyzed using
Wilcoxon Signed Rank and Mann-Whitney U tests (P > 0.05). RESULTS: The severity
of pain was lower in infiltration technique versus I.A nerve block. There were no
significant differences between the severities of pain on pulpal exposure of two
techniques. CONCLUSION: It seems that infiltration technique is more favorable to
anesthetize the mandibular primary first molar compared to I.A nerve block.
PMID- 24348620
TI - The effect of adjunctive low-dose doxycycline and licorice therapy on gingival
crevicular fluid matrix metalloproteinase-8 levels in chronic periodontitis.
AB - BACKGROUND: This study compared the effect of adjunctive low dose doxycycline and
licorice on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8)
levels in patients with chronic periodontitis. MATERIALS AND METHODS: In this in
vivo, experimental study 39 patients with mild to moderate chronic periodontitis
were selected. Samples of GCF were collected from three deepest pockets and MMP-8
concentration was measured. Patients were divided into three groups (n = 13).
Groups were treated with doxycycline, licorice and placebo. Sampling and
measurement of MMP-8 was repeated after 6 weeks. Data was analyzed by t-paired
and ANOVA test. P > 0.001 was considered significant. RESULTS: The decrease in
mean of MMP-8 concentration was higher in doxycycline and licorice group in
comparison with the placebo group and the difference was statistically
significant (P value > 0.001). The decrease in mean of MMP-8 concentration was
higher in licorice group than doxycycline group, but the difference was not
statistically significant. CONCLUSION: The present study showed that licorice
extract can prevent the production of MMPs by host cells and can be as useful as
antibiotics like doxycycline to cure periodontal and other inflammatory diseases.
It must be added that no side-effects were observed in usage of licorice extract.
PMID- 24348621
TI - The effect of ovalbumin on orthodontic induced root resorption.
AB - BACKGROUND: This randomized trial was undertaken to investigate the effect of
experimentally induced allergy on orthodontic induced root resorption. MATERIALS
AND METHODS: A total of 30 Wistar rats were divided randomly into test and
control groups. Starting from the first 3 days, the rats in the test group were
injected intra-peritoneally by 2 mg ovalbumin as allergen and 0.5 mg Alume as
adjuvant. Afterward only allergen was injected once a week. The control group was
injected by normal saline. After 21 days, Wistar immunoglobulin E was measured
and peripheral matured eosinophil was counted. A total of 50 g nickel-titanium
closed coil spring was ligated between right incisor and first molar. All animals
were sacrificed after 14 days. The mesial root of the right and left first molar
was dissected in a horizontal plane. The specimens were divided into four groups
considering whether force and/or ovalbumin was applied or not. Root resorption
was measured and compared among these groups. Repeated measures analysis of
variance (ANOVA), and Bonferoni tests were used to analyze the data. The level of
significance was determined at 0.05. RESULTS: In general, the differences were
insignificant (P < 0.05). As the only exception, the group in which both
ovalbumin and force were applied had significantly more root resorption than the
group in which neither force nor ovalbumin was applied (P > 0.001). CONCLUSION:
Allergy may increase the susceptibility to root resorption. Application of light
force, periodical monitoring of root resorption and control of allergy are
advisable.
PMID- 24348622
TI - Evaluation of orthodontic treatment need by patient-based methods compared with
normative method.
AB - BACKGROUND: A comprehensive system of assessing orthodontic need requires the
integration of normative clinical measures with patient-based indicators. This
study sought to discover weather an oral health-related quality of life measure
or Aesthetic Component of Index of Orthodontic Treatment Need (AC-IOTN) could be
used as a predictor of orthodontic treatment need. Factors affecting the judgment
of patient and dentist about this need are discussed. MATERIALS AND METHODS: Oral
examination on 597 Iranian students between 13 years and 18 years was done to
reach the grade of Dental Health Component (DHC). The Child Oral Health Impact
Profile (COHIP) and AC-IOTN were recorded. The diagnostic values of subjective
tests were assessed. Multiple logistic regressions were applied to investigate
the role of variables in the persons' perceptions. RESULTS: Half of the 570
eligible students did not need orthodontic treatment either on professional or
self-assessment; 60% of patients with definite need had a distinct impact on
their quality of life. The specificity of AC to detect the healthy persons was
excellent (0.99) but its sensitivity was low (0.08). COHIP score gave a better
sensitivity but its specificity was 50%. Caries experience, quality of life,
father's education, and brushing habits were the factors relating to the same
judgment of persons and dentists (P > 0.02). CONCLUSION: Regarding the
discrepancies between two assessment methods, present instruments did not meet
the predictor's competencies. The patient-based methods could not substitute the
professional assessment, but by identification, the persons with higher impacts
would benefit the prioritization process.
PMID- 24348623
TI - Microleakage assessment of fissure sealant following fissurotomy bur or pumice
prophylaxis use before etching.
AB - BACKGROUND: A prolonged life of fissure sealant has always been the target for
preventing caries in vulnerable newly erupted teeth. The use of preparatory
techniques including bur introduction to the fissures is considered among such
improving steps. MATERIALS AND METHODS: Ninety freshly extracted healthy
maxillary premolar teeth were randomly selected for this investigation. Teeth
were then divided into three fissure sealant preparatory groups of A: Fissurotomy
bur + acid etch; B: Pumice prophylaxis + acid etch and C: Acid etch alone.
Sealant was applied to the occlusal fissures of all specimens using a plastic
instrument. This was to avoid any air trap under the sealant. Sample teeth were
first thermocycled (1000 cycles, 20 s dwell time) and then coated with two layers
of nail varnish leaving 2 mm around the sealant. This was then followed by
immersion in basic fuchsin 3%. Processed teeth were sectioned longitudinally and
examined under a stereomicroscope for microleakage assessment using a score of 0
3. Collected data was then subjected to Kruskall-Wallis Analysis of Variance and
Mann-Whitney U-test. P > 0.05 was considered as significant. RESULTS: Teeth in
fissurotomy bur and pumice prophylaxis groups had significantly reduced level of
microleakage than those in acid etch alone (P = 0.005 and P = 0.003,
respectively). CONCLUSION: Use of fissurotomy bur and pumice prophylaxis
accompanied with acid etching appears to have a more successful reduction of
microleakage than acid etch alone.
PMID- 24348624
TI - Effect of low-level laser therapy on dental pain induced by separator force in
orthodontic treatment.
AB - BACKGROUND: Patients undergoing orthodontic treatment experience varying degrees
of pain with separator insertion. A survey of patients' attitude towards
orthodontic treatment revealed that pain was the most discouraging factor related
to their treatment. Moreover, it was the highest ranking reason for wanting to
discontinue care. The purpose of this study was to determine the effect of low
level laser irradiation on dental pain induced by forces from separators in
orthodontic treatment. MATERIALS AND METHODS: This study was an experimental
clinical trial. Twenty-nine patients were recruited for this research. Low-level
laser irradiation was applied on one half of the maxillary and mandibular arches
for 5 days. The opposite half of the arches was considered the control group.
Laser irradiation was applied for 30 seconds in the alveolar bone between the
second premolars, first molars, and second molars. Pain perception was evaluated
with a standardized questionnaire that was answered by patients before and after
laser irradiation. Data was analyzed by Wilcoxon and Friedman test. P value
<=0.05 was considered significant. RESULTS: The highest pain level was reported
at day 1 following separator placement and decreased gradually until day 5. At
day 4 and 5, the pain intensity was lower in the laser group than in the control
group; however, this finding was not statistically significant. At day 1 and 3,
the pain intensity was higher in the laser group than in the control group;
however, it was not statistically significant. At day 2, the pain intensity was
lower in the laser group than in the control group and was statistically
significant. CONCLUSION: Our findings suggest that there is no statistically
significant difference in pain by using low-level laser irradiation.
PMID- 24348625
TI - In vivo biocompatibility of Resilon compared with gutta-percha in a pre-clinical
model.
AB - BACKGROUND: The aim of this study was to investigate in vivo biocompatibility of
Resilon, compared with gutta-percha, at short and long-term following
implantation in a rat subcutaneous implantation model. MATERIALS AND METHODS:
Male Wistar rats were implanted subcutaneously with either Resilon or gutta
percha or were sham controls. Tissues were harvested at 8 days or 60 days after
implantation and were evaluated histologically for inflammation and fibrous
encapsulation. The severity of histologic injury, scored on a scale of 0-4 and
quantitative analysis of the capsule wall thickness were determined for
statistical analysis. Data were analyzed by Student t-test, one-way analysis of
variance, Kruskal-Wallis or Mann-Whitney's tests as appropriate. A value of P <=
0.05 was considered statistically significant. RESULTS: No behavioral changes or
visible signs of physical impairment were observed at 8 days or 60 days post
implantation. Histopathologic observation of the implanted sites at each time
point showed that both Resilon and gutta-percha implants induced foreign body
reaction, showing minimal to mild inflammatory reactions in most cases, which
diminished significantly with time. Compared with gutta-percha, the capsule wall
was thinner (P < 0.05) after Resilon implantation at day 8 and significantly (P =
0.01) thicker at day 60. In addition, capsule wall thickness showed a trend to
increase with time after implantation in the Resilon groups (P < 0.05), opposed
to the significant decrease (P = 0.016) observed after implantation in the gutta
percha groups, suggesting lesser long-term biocompatibility of Resilon.
CONCLUSION: Our findings validate Resilon as an in vivo biocompatible material.
However, our data suggest that long-term biocompatibility of Resilon, despite
validated, is inferior to that of gutta-percha control.
PMID- 24348626
TI - Infant oral health: Knowledge, attitude and practices of parents in Udaipur,
India.
AB - BACKGROUND: The aim of this study was to assess the infant oral health (IOH)
related knowledge, attitudes and practices (KAP) of parents in Udaipur, India.
MATERIALS AND METHODS: A cross-sectional descriptive study was conducted among
470 parents visiting the Department of Pediatrics, Rabindranath Tagore Medical
College and Hospital. A 32-item questionnaire covering socio-demographic
characteristics and questions pertaining to KAP regarding IOH care was used to
collect the data. Descriptive statistics, Student's t-test, one-way analysis of
variance, and Scheffe's test were used for the statistical analysis (P <= 0.05).
RESULTS: Majority of the parents had good knowledge regarding tooth eruption, but
had a poor knowledge of cleaning (58.7%) and development of caries (48.5%).
Parents in the age group of 25-30 years showed significantly higher mean
knowledge (25.90 +/- 3.93), attitude (15.71 +/- 2.23), and practice (20.09 +/-
2.50) scores. Female parents showed a significantly higher mean knowledge (21.45
+/- 4.27) and attitude scores (14.97 +/- 2.15) than the male parents. CONCLUSION:
Parent's knowledge on IOH care was inadequate. Health professionals, who are the
first to come into contact with expectant and new mothers, need to disseminate
appropriate and accurate information about oral health-care for infants.
PMID- 24348627
TI - Clinical and radiological assessment of effects of long-term corticosteroid
therapy on oral health.
AB - BACKGROUND: Corticosteroids (Cs) are used widely for their anti-inflammatory and
immunosuppressive properties. They have the potential to cause dramatic
improvement as well as produce equally dramatic adverse effects. The clinical
misuse like over prescription of the drug should be avoided. Long-term
administration may cause many adverse effects leading to impaired oral health.
Oral health is usually not considered during management of patients on long-term
corticosteroid therapy. The aim of this study was to assess the oral health
status and radiological changes in the jaw bones of the patients under long-term
corticosteroid therapy. MATERIALS AND METHODS: Oral health of 100 patients under
long-term corticosteroid therapy with a minimum of 3 months duration was compared
with sex- and age-matched 100 healthy controls. The clinical examination included
complete examination of the mouth and periodontal status. Radiographic evaluation
of bone with the help of intra oral periapical radiograph and digital
orthopantomograph and levels of serum calcium, alkaline phosphatase, and random
blood sugar were assessed. 'Chi-square test', 'Kolmogorov-Smirnov test' and 'Mann
Whitney U test' were used for statistical analysis. P > 0.05 was considered
significant. RESULTS: Patients on steroids exhibited significantly higher levels
of candidiasis and clinical attachment loss of the periodontal ligament, probing
pocket depth. Bone density was significantly lower in the study group than that
in the control group. Random blood glucose was significantly higher and
significant lower levels of calcium were observed in patients on steroids.
CONCLUSION: Long-term use of Cs may affect oral health adversely leading to
candidiasis as well as impair bone metabolism leading to a considerable decrease
in the mandibular bone mineral density.
PMID- 24348628
TI - An unusual triad: Bilateral dilated odontoma, hypodontia and peg laterals.
AB - The dilated odontoma is an infrequent developmental alteration that appears in
any area of the dental arches and can affect deciduous, permanent and
supernumerary tooth. Dens invaginatus is a developmental anomaly resulting from
invagination of a portion of crown forming within the enamel organ during
odontogenesis. The most extreme form of dens invaginatus is known as dilated
odontoma. The aim of this case report is to present a rare case of bilateral
dilated odontoma affecting a microdontic permanent lateral incisor in a 30 year
old female patient with hypodontia and peglateral teeth with its clinical,
radiological and histological features, which has yet been not reported.
Bilateral presence of dilated odontoma is not a common occurrence, although a
single tooth involvement in each case has been reported in the literature.
PMID- 24348630
TI - Mucinous cystadenoma: A rare entity.
AB - Cystadenoma is a rare benign salivary gland tumor that chiefly originates in the
minor salivary glands as a cystic growth with papillary projections into the
cystic lumen without the lymphoid element. It is further classified into two
histopathological variants that have been recognized by World Health Organization
as the papillary and the mucinous forms of cystadenoma. Clinically, it is
difficult to differentiate from other benign minor salivary tumors and mucous
retention phenomenon. Diagnosis is chiefly based on characteristics histological
features. It is believed that the salivary gland tumors are difficult to diagnose
and interpret because there are varied patterns of presentation. The study of
salivary gland disorders has increased in leaps and bounds. The authors report a
case of mucinous cystadenoma of the minor salivary gland on the hard palate,
which is even rarest of the rarely reported cystadenomas of the minor salivary
glands.
PMID- 24348629
TI - Rapid, conservative, multidisciplinary miniscrew-assisted approach for treatment
of mandibular fractures following plane crash.
AB - Mandibular fractures are among the most common facial injuries. This case report
demonstrates the efficacy of simultaneous usage of miniscrews and direct bonding
techniques without open reduction in an extensive traumatized patient. A 25-year
old girl with multiple injuries in the head and facial region 1 month after a
plane crash accident was referred to manage the mandibular fractures. Due to the
presence of multiple injuries, a conservative treatment of symphysiseal fracture
was performed. In order to keep the fractured fragments of the mandible close
together, the anterior teeth of the lower arch were tied by means of the
orthodontic wire. Ten miniscrews were used to improve the anchorage units and
also, settling the occlusion by means of light intermaxillary elastics. Following
the active treatment, clinical and radiographic analysis showed satisfactory
healing without any periodontal involvement of the teeth in the fracture line.
PMID- 24348631
TI - Treatment strategy for guided tissue regeneration in various class II furcation
defect: Case series.
AB - Periodontal regeneration is a main aspect in the treatment of teeth affected by
periodontitis. Periodontal regeneration in furcation areas is quite challenging,
especially when it is in interproximal region. There are several techniques used
alone or in combination considered to achieve periodontal regeneration, including
the bone grafts or substitutes, guided tissue regeneration (GTR), root surface
modification, and biological mediators. Many factors may account for variability
in response to regenerative therapy in class II furcation. This case series
describes the management of class II furcation defect in a mesial interproximal
region of a maxillary tooth and other with a buccal class II furcation of
mandibular tooth, with the help of surgical intervention including the GTR
membrane and bone graft materials. This combined treatment resulted in healthy
periodontium with a radiographic evidence of alveolar bone gain in both cases.
This case series demonstrates that proper diagnosis, followed by removal of
etiological factors and utilizing the combined treatment modalities will restore
health and function of the tooth with the severe attachment loss.
PMID- 24348632
TI - A procedure for recording and reproducing the cast position on a surveyor.
PMID- 24348633
TI - Normal limit for serum alanine aminotransferase level and distribution of
metabolic factors in old population of kalaleh, iran.
AB - BACKGROUNDS: Normal or elevated values of serum alanine aminotransferase level
(ALT) vary in different studies mostly related to characteristics of reference
population including age, gender, body mass index, nonalcoholic fatty liver
disease (NAFLD), and metabolic syndrome prevalence. OBJECTIVES: To measure upper
normal limit (UNL) for serum ALT in an apparently healthy Iranian old population
(which we had not sufficient data before this study), and its modulating factors.
PATIENTS AND METHODS: All inhabitants (> 50 years old) of Kalaleh, Golestan, Iran
(N = 1986) were invited to the study. ALT measurements were performed for all
subjects using the same laboratory method. Upper limit of normal (ULN) ALT was
calculated based on its 95th percentile in normal weight subjects. Modulating
factors of ALT were determined by multivariate analysis. RESULTS: A total of 1309
subjects, with the mean age of 61.5 +/- 7.5 years were included. UNL of ALT was
18.8 U/L and 21.4 U/L in women and men, respectively. Based on univariate
analysis, waist circumference (r = 0.124, P = 0.01), body mass index (r = 0.118,
P = 0.01), triglyceride (r = 0.143, P = 0.01), and having metabolic syndrome (OR
= 2.04) modulate ALT levels in men. Also triglyceride (r = 0.119, P = 0.01)
modulates ALT levels in women. CONCLUSIONS: The calculated level for UNL of ALT
is considerably far lower than previous accepted value. Age, gender, ethnicity,
and metabolic factors should be accounted in future studies to determine normal
ALT level.
PMID- 24348634
TI - Evaluation of PCR-RFLP in the Pre-S Region as Molecular Method for Hepatitis B
Virus Genotyping.
AB - BACKGROUND: Hepatitis B virus (HBV) infection is a public health problem in
developing countries. HBV genotypes play major role in the evolution of infection
since they were involved in different clinical presentations and response to
treatment. OBJECTIVES: This study was conducted to evaluate the efficiency of
restriction fragment length polymorphism (RFLP) analysis for HBV genotyping.
PATIENTS AND METHODS: We investigated 98 samples collected from patients
chronically infected with HBV. HBV genotypes were determined by analysis of
patterns obtained after amplification in Pre-S region and digestion of the
amplicon by two endonucleases AvaII and DpnII. Obtained results were confirmed by
partial sequencing in the same region. RESULTS: Two different HBV genotypes were
detected in this study, Genotype D (in 95. 9%) and Genotype A (in 4.1%). Seventy
four samples (75.5%) were successfully genotyped with RFLP analysis and all
classified as genotype D. The remaining 24 samples (24.5%) which were un
genotyped by RFLP analysis, were classified by partial sequencing of the pre-S
region as HBV genotype D (20 samples, 20.4%) and genotype A (4 samples, 4.1%).
Atypical profiles were significantly associated with advanced liver disease (P =
0.001) as well as older age (P < 0.05). CONCLUSIONS: Several previous studies
used PCR-RFLP to genotype HBV; however, we showed the high risk to obtain
atypical profiles, especially in advanced stages of chronic infection, with as
results difficulties to genotype the virus. These profiles resulted from the
accumulation of mutations during natural course of infection resulting in a
modification in restriction sites for enzymes. So, we recommended completing the
investigation by partial sequencing to confirm obtained results.
PMID- 24348635
TI - Baseline high viral load and unfavorable patterns of alanine aminotransferase
change predict virological relapse in patients with chronic hepatitis C genotype
1 or 2 obtaining rapid virological response during antiviral therapy.
AB - BACKGROUND: Rapid virological response (RVR) strongly predicts sustained
virological response (SVR) in patients with chronic hepatitis C (CHC), and
abbreviates antiviral therapy in some patients. OBJECTIVES: To identify factors
predicting virological relapse (VR) in CHC patients who attained RVR. PATIENTS
AND METHODS: Medical records of 133 CHC patients with an RVR after completing 24
weeks of antiviral therapy (a combination of pegylated interferon-alpha and
ribavirin) were analyzed. Baseline characteristics and on-treatment responses
were compared between the patients with an SVR and those with VR. Patients with
normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of
treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels
were classified as having favorable patterns of ALT change. A trend of increasing
ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was
classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV
RNA >= 600000 IU/mL. RESULTS: In total, 116 (87.2%) patients had a SVR and 14
(10.5%) had VR. The VR rates were comparable between patients with genotype-1
(13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis
revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval
(CI) = 1.671-130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95%
CI = 1.078-17.930) independently predicted VR. In subgroup analysis, low viral
load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR
rate of those using peg-IFN-alpha-2a was relatively low (9.1%). Patients using
peg-IFN-alpha-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients
with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to
the 53.8% in patients with unfavorable ALT patterns (P = 0.005). CONCLUSIONS: In
southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in
patients with CHC attaining RVR, except in the subgroup of patients treated with
peg-IFN-alpha-2b with HVL and on-treatment unfavorable ALT patterns.
PMID- 24348637
TI - Substitution rtq267h of hepatitis B virus increases the weight of replication and
Lamivudine resistance.
AB - BACKGROUND: Nucleus(t)ide analogs (NAs), containing Lamivudine (LMV), adefovir
dipivoxil (ADV), endeavor (ETV), telbivudine (LdT), and tenofovir (TDF) are
widely used for the treatment of chronic hepatitis B (CHB), but long term anti
Hepatitis B virus (HBV) therapy with NAs may give rise to the emergence of drug
resistant viral mutants. OBJECTIVES: This study aimed to find and identify some
new resistance mutations of HBV from the patients accepted anti-HBV therapy.
PATIENTS AND METHODS: The reverse transcriptase (RT) coding region of HBV was PCR
amplified using HBV DNA extracted from patients' blood samples and sequenced.
RESULTS: Nineteen substitution mutations were detected. Among them, rtQ267H was
often observed in patients receiving LMV administration. This LMV therapy-related
mutation was introduced into HBV replication-competent plasmids. The in vitro
susceptibility of both wild-type (WT) and mutant-type (MT) HBV to NAs was
analyzed by Southern blot, and/or quantitative real-time PCR (qRT-PCR). The
rtQ267H substitution enhanced HBV replication not merely in single-site mutation,
but also in multisite mutations. The in vitro susceptibility analysis showed that
the existence of rtQ267H in WT and LMV-resistant (LMVr) HBV were responsible for
the reduced susceptibility to LMV to varying degrees, and enhanced HBV
replication capacity. However, HBV harbored this substitution retained normal
susceptibility to ADV, LdT, ETV, and TDF. CONCLUSIONS: The result suggested that
rtQ267H is a potential adaptive mutation of HBV to LMV.
PMID- 24348636
TI - The role of celiac disease in severity of liver disorders and effect of a gluten
free diet on diseases improvement.
AB - CONTEXT: Celiac disease (CD) is defined as a permanent intolerance to ingested
gluten. The intolerance to gluten results in immune-mediated damage of small
intestine mucosa manifested by villous atrophy and crypt hyperplasia. These
abnormalities resolve with initiationa gluten-free diet. EVIDENCE ACQUISITION:
PubMed, Ovid, and Google were searched for full text articles published between
1963 and 2012. The associated keywords were used, and papers described
particularly the impact of celiac disease on severity of liver disorder were
identified. RESULTS: Recently evidence has emerged revealingthat celiac disease
not only is associated with small intestine abnormalities and malabsorption, but
is also a multisystem disorder affecting other systems outside gastrointestinal
tract, including musculo-skeletal, cardiovascular and nervous systems. Some
correlations have been assumed between celiac and liver diseases. In particular,
celiac disease is associated with changes in liver biochemistry and linked to
alter the prognosis of other disorders. This review will concentrate on the
effect of celiac disease and gluten-free diets on the severity of liver
disorders. CONCLUSIONS: Although GFD effect on the progression of CD associated
liver diseases is not well defined, it seems that GFD improves liver function
tests in patients with a hypertransaminasemia.
PMID- 24348638
TI - Serum iron markers in patients with chronic hepatitis C infection.
AB - BACKGROUND: Patients with chronic hepatitis C (CHC) often have elevated serum
iron markers, which may worsen liver injury. OBJECTIVES: The aim of this study
was to investigate the possible correlations between iron metabolism serum
markers, HCV viral load, and liver disease severity in treatment-naive patients
with chronic hepatitis C infection. PATIENTS AND METHODS: Eighty five patients
with untreated hepatitis C chronic infection were investigated. RESULTS: Twenty
one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had
severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and
ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were
detected in patients with severe fibrosis compared to no/mild fibrosis. Severe
necroinflammatory activity was also significantly correlated with serum iron (P <
0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear
regression analysis, serum levels of ferritin and transferrin were the
independent variables selected as being good predictors for advanced fibrosis and
severe necroinflammatory activity. No significant correlations were detected
between HCV viral load and iron markers. CONCLUSIONS: This study revealed that
serum iron markers (especially ferritin and transferrin) might be used as
surrogate markers for both liver fibrosis and necroinflammatory activity.Patients
with chronic hepatitis C (CHC) often have elevated serum iron markers, which may
worsen liver injury.
PMID- 24348639
TI - Hepatitis B: knowledge, vaccine situation and seroconversion of dentistry
students of a public university.
AB - BACKGROUND: Viral hepatitis B (VHB) is an occupational risk for dentists. It is
necessary that dental students start clinical practice immunized with the
vaccine, response monitored and informed about the means of transmission of the
disease. Rarely, there are studies, which evaluate concomitantly knowledge of
these academics and their vaccine situation. OBJECTIVES: To evaluate the
knowledge about Hepatitis B, the vaccine situation and the immunization status of
dental students and to investigate the probable correlation between the status of
immunization, vaccination membership and adherence to the test of seroconversion
and associated factors. PATIENTS AND METHODS: 189 students from the dentistry
course at the Federal University of Piaui (UFPI) who attended from the 3rd to 9th
period were invited to participate in the research. Their knowledge about HBV,
attitude regarding protection and their vaccine situation were assessed through a
self-administered form. Antibodies against surface antigens of Hepatitis B virus
(Anti-HBs) and against the antigens of the virus nucleous of Hepatitis B (Anti
HBc total) were measured qualitatively using the enzyme-linked immunosorbent
assay (ELISA). RESULTS: Of the 179 students surveyed, 58.1% knew about the degree
of virulence of the Hepatitis B virus (HBV). As to the means of transmission,
98.3% considered blood transmission, 82.6% plates and cutlery, 15.6% cough and
12.3% vertical transmission. Most students (87.4%) knew that they should take 3
doses of the vaccine and 62.2% completed the immunization schedule. A minority of
students (48.6%) knew the about the Anti-HBs test and 5.6% took the test. Among
the students who reported having taken three doses of the vaccine, 12.5% were not
seroconverted. There was no significant correlation between the variables.
CONCLUSIONS: Dental academics were unsure about the means of infection and
prevention against HBV. Many of them had not completed the immunization scheme
and did not have the test of seroconversion. The serological analysis revealed
unprotection, even after students completed the vaccination schedule.
PMID- 24348640
TI - The Relationship between Intestinal Motility and Interstitial Cells of Cajal in
Nonalcoholic Fatty Liver Mice.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of
chronic liver disease in western world. However, NAFLD shows an increasing trend
in China every year, which has attracted the attention of national health
authorities. The previous studies have shown that NAFLD caused severe
gastrointestinal motor disorders, but little is known about the interstitial
cells of Cajal (ICC) role in gastrointestinal motor disorders. OBJECTIVES: The
aim of this study was to observe the ICC in jejunum of nonalcoholic fatty liver
mice by immunohistochemistry and assessed the relationship between intestinal
motility and ICC. MATERIALS AND METHODS: Thirty five Sprague-Dawley (SD) rats
were randomly divided into nonalcoholic fatty liver (n = 25) and control groups
(n = 10), rats were housed individually in cages and had free access to food and
water, nonalcoholic fatty liver group was duplicated by high-fat diet (consisted
of ordinary food, 20 g/kg cholesterol and 100 g/kg fat) feeding. Dextran blue
2000 was used to monitor the intestinal motility. The proximal small intestine
was harvested to investigate the C-kit positive ICC. The hepatic tissue slices
were used for pathological observation. RESULTS: Nonalcoholic fatty liver disease
was successfully established. The intestinal motility in nonalcoholic fatty liver
group (49.5 +/- 10.9) was weaker compared to the control group (57.3 +/- 8.9), P
< 0.05. The rate of ICC also have shown statistically significant differences
between nonalcoholic fatty liver (4.87 +/- 2.97/mm (2)) and control groups (6.54
+/- 3.13/mm (2)), P < 0.05. CONCLUSIONS: ICC may be related to the intestinal
motility in nonalcoholic fatty liver mice.
PMID- 24348642
TI - Liver Transplantation for Quality as well as Quantity of Life.
PMID- 24348641
TI - Immunization of Mice by BCG Formulated HCV Core Protein Elicited Higher Th1
Oriented Responses Compared to Pluronic-F127 Copolymer.
AB - BACKGROUND: A supreme vaccine for Hepatitis C virus (HCV) infection should elicit
strong Th1-oriented cellular responses. In the absence of a Th1-specific
adjuvant, immunizations by protein antigens generally induce Th2-type and weak
cellular responses. OBJECTIVES: To evaluate the adjuvant effect of BCG in
comparison with nonionic copolymer-Pluronic F127 (F127) as a classic adjuvant in
the formulation of HCV core protein (HCVcp) as a candidate vaccine for induction
of Th1 immune responses. MATERIALS AND METHODS: Expression of N-terminally His
Tagged HCVcp (1-122) by pIVEX2.4a-core vector harboring the corresponding gene
under the control of arabinose-inducible (araBAD) promoter was achieved in BL21
AI strain of E.coli and purified through application of nitrilotriacetic acid (Ni
NTA) chromatography. Mice were immunized subcutaneously (s.c.) in base of the
tail with 100 MUl of immunogen (F127+HCVcp or BCG+HCVcp; 5 MUgHCVcp/mouse/dose)
or control formulations (PBS, BCG, F127) at weeks 0, 3, 6. Total and subtypes of
IgG, as well as cellular immune responses (Proliferation, In vivo CTL and IFN
gamma/IL-4 ELISpot assays against a strong and dominant H2-d restricted, CD8+
epitopic peptide, core 39-48; RRGPRLGVRA of HCVcp) were compared in each group of
immunized animals. RESULTS: Expression and purification of core protein around
the expected size (21 kDa) was confirmed by Western blotting. The HCVcp + BCG
vaccinated mice showed significantly higher lymphocyte proliferation and IFN
gamma production but lower levels of cell lysis (45% versus 62% in CTL assay)
than the HCVcp+F127 immunized animals. "Besides, total anti-core IgG and IgG1
levels were significantly higher in HCVcp + F127 immunized mice as compared to
HCVcp + BCG vaccinated animals, indicating relatively higher efficacy of F127 for
the stimulation of humoral and Th2-oriented immune responses". CONCLUSIONS:
Results showed that HCVcp + BCG induced a moderate CTL and mixed Th1/Th2 immune
responses with higher levels of cell proliferation and IFN-gamma secretion,
indicating that BCG may have a better outcome when formulated in HCVcp-based
subunit vaccines.
PMID- 24348643
TI - Liver transplant recipients quality of life instrument: development and
psychometric testing.
AB - BACKGROUND: Liver transplantation is a life-saving intervention for many patients
with end-stage liver disease. In the past, evaluation of successful liver
transplantation was based on patients' survival rate. However, in recent years
this evaluation has been based on patients' quality of life. Various instruments
have been developed to evaluate patients' quality of life. Nonetheless, scholars
still believe that it is crucial to develop a standardized and disease specific
instrument for evaluating the quality of life in liver transplant recipients.
OBJECTIVES: The aim of this paper was to describe the development and
psychometric testing process of a quality of life instrument specific to liver
transplant recipients. MATERIALS AND METHODS: Initial items of this instrument
were extracted from a conventional content analysis study, and then were
completed with findings of related international literature. The face validity
was assessed by interviewing with four liver transplant recipients, and the
content validity was evaluated by eleven experts in the field of transplantation.
The construct validity was achieved by involving 250 liver transplant recipients
through exploratory factor analysis method, and reliability was calculated by
Cronbach's alpha. RESULTS: Three main factors with 40 items were extracted from
the exploratory factor analysis: Health Satisfaction, Concerns, and
Complications. Reliability of the instrument was confirmed (alpha = 0.922).
CONCLUSIONS: Given the special considerations regarding liver transplant
recipients, this questionnaire is more accurate in evaluating the success of
liver transplantation.
PMID- 24348644
TI - Seroprevalence of hepatitis e among pregnant women in urmia, iran.
AB - BACKGROUND: While hepatitis E virus (HEV) mostly causes self-limited disease in
general population, it is more severe in pregnant women. OBJECTIVES: This study
aimed to investigate the seroprevalence of anti-HEV IgG among a population of
pregnant women in West Azerbaijan of Iran . PATIENTS AND METHODS: One hundred
thirty six pregnant women referred to urban health centers of Urmia for pursuing
pregnancy-related health services were enrolled in a descriptive, cross-sectional
study. Anti-HEV IgG antibody was evaluated using enzyme-linked immunosorbent
assay (enzyme-linked immunosorbent assay, ELISA; Dia.Pro; Diagnostic Bioprobes).
RESULTS: Only five (3.6%) of 136 cases had positive results for anti-HEV IgG.
There was no significant difference between age (P=0.88), and income level (P =
0.19) of the two seropositive and seronegative groups. All seropositive cases
were from urban areas. CONCLUSIONS: The seroprevalence of anti-HEV IgG is low in
the population of pregnant women in , similar to the rates reported from
developed countries. Effective health services and provision of safe water
supplies in Urmia may take role in this low prevalence rate.
PMID- 24348645
TI - Impact of Pegylated Interferon-alfa-2a on Perforin Level in Patients With Chronic
Hepatitis B; Preliminary Study.
AB - BACKGROUND: Chronic hepatitis B is one of the most common causes of cirrhosis and
hepatocellular toxicity in many countries, including Iran. Cytotoxic T lymphocyte
(CTL) and Natural killer (NK) cells are the two of main cell populations
considered as cytotoxic cells. One of the distinct pathways CTL and NK cells
exert cytotoxicity is perforin/granzyme. After the cytotoxic cell/target cell
junction, perforin is released from granules by exocytosis. Once it is anchored,
perforin forms cylindrical pores through which granzymes and granulysin enter and
induce apoptosis. OBJECTIVES: Large controlled trials have demonstrated the
efficacy of PEG-IFN-alpha-2a in treatment of chronic hepatitis B. This study was
aimed to examine whether the enhancement of cytotoxicity by PEG-IFN-alpha-2a is
mainly due to the perforin pathway. PATIENTS AND METHODS: This research work was
performed on 50 patients and five healthy people. Patients with chronic hepatitis
B were further subdivided into two groups: patients with inactive chronic
hepatitis B (carriers, n = 30), and those with active chronic hepatitis B who
were under treatment with PEG-IFN-alfa-2a (n = 20) for minimum six and maximum 12
months. Serum perforin level was measured using ELISA method (CUSABIO Company),
HBV viral load was assessed using COBAS Taq-man, and we used Elecsys hepatitis B
surface antigen (HBs Ag) II quantitative assay method for HBs Ag determination.
HBeAg was evaluated by ELISA method, and AST and ALT were measured by routine
laboratorymethods. RESULTS: Based on the results obtained serum perforin level in
healthy group was 0.64 ng/mL, the mean of serum perforin level in inactive HBs Ag
carriers was 2.63ng/mL, and 4.63 ng/mL in patients with active chronic hepatitis
B under treatment with PEG-IFN-alpha-2a. The mean of serum perforin level in
patients with and without virologic response to treatment were 5.45 ng/mL,and 3.4
ng/mL respectively. Finally in patients with virologic response and seroconverted
serum perforin level was 7.23 ng/mL. CONCLUSIONS: Based on our results higher
perforin level in patients under treatment with PEG-IFN-alpha-2a, could be an
indication of elevated cytotoxicity via perforin/granzyme pathway.
PMID- 24348646
TI - Cholestasis and seizure due to lead toxicity: a case report.
AB - INTRODUCTION: Lead poisoning is a major public health risk which may involve
major organs. Recently, there have been reports of opioid adulteration with lead
in Iran. The following case report is the first of its kind in that intrahepatic
cholestasis due to lead toxicity has been described. CASE PRESENTATION: A 65-year
old man presented to the emergency department with abdominal pain, abnormal liver
function tests (cholestatic pattern), and normocytic anemia. He had been an opium
user for 20 years. Clinical and preclinical findings including the bluish
discoloration of periodontal tissues, or Burton's sign, and generalized ileus on
abdominal x-ray led us to the possibility of lead poisoning. Lead levels were
higher than normal (150 MUg/dL). Magnetic resonance cholangiopancreatography
(MRCP) and abdominal ultrasound were performed to rule out extra hepatic causes
of cholestasis. To evaluate the possibility of lead-induced hepatotoxicity, a
liver biopsy was performed. Histological features of lead-induced hepatotoxity
have rarely been described in humans. In this patient, focal canalicular
cholestasis and mild portal inflammation were confirmed. Thus, treatment with
ethylenediaminetetraacetic acid (EDTA) and British anti-lewisite (BAL) were
initiated and continued for five days. The patient's liver function tests
returned to their normal values, clinical findings including nausea, vomiting,
and abdominal pain subsided, and the patient was discharged from the hospital in
good condition. CONCLUSIONS: Lead toxicity should always be taken into account in
cases of intrahepatic cholestasis with an unknown etiology, especially in a
setting where opium abuse is common.
PMID- 24348647
TI - Sexual Transmission of Hepatitis C Virus Between HIV Infected Subjects and Their
Main Heterosexual Partners.
AB - BACKGROUND: Overall, 60-70% of the hepatitis c virus (HCV) transmission routes is
parenteral, and in 30-40% of the cases is unknown (e.g. sexual route). Knowing
these routes in HIV infected dyads is very important due to clinical and
methodological reasons. OBJECTIVES: The present study aimed to identify and
quantitatively investigate HIV-infected individuals and their main heterosexual
partners regarding the risk factors of HCV transmission. PATIENTS AND METHODS:
One hundred sixty eight of 984 couples were chosen through random generated
numbers using a computer program from behavioral consultation center in Shiraz,
Iran. We used actor partner independent model (APIM) and multilevel analysis to
assess multiple risk factors for HCV, while partitioning the source of risk at
the individual and couple levels. RESULTS: Age of the index samples was 38.71 +/-
7 years, and 33.2 +/- 6.3 for their main heterosexual partners; the mean duration
of sexual relationship for couples was 11.9 (median = 8.5) years. Multivariate
analysis showed that actor risk factor of intravenous drug using (IDU) (AOR=
13.03; 95% CI: 3.9- 43.82) and actor cofactors of HIV positivity (AOR = 7.1; 95%
CI: 1.37- 36.97), razor sharing (AOR = 4.81; 95% CI: 1.84- 12.55), sex (AOR =
8.83; 95% CI: 3.16- 24.87), and condom use in sexual activity with main partner
(AOR = 0.15; 95% CI: 0.02- 0.44) were associated with actor HCV positivity.
CONCLUSIONS: Health care providers need to pay special attention to sexual
transmission of HCV among HIV-infected individuals, and should recommend
control/preventive measures for HCV sexual transmission.
PMID- 24348648
TI - Association of IL28B Polymorphisms With the Response to Peginterferon Plus
Ribavirin Combined Therapy in Polish Patients Infected With HCV Genotype 1 and 4.
AB - BACKGROUND: Three single nucleotide polymorphisms (SNPs) near interleukin-28B (IL
28B) gene were shown to be highly associated with treatment response (SVR) in
patients with chronic hepatitis C virus (HCV) infection. There is limited data
about the role of single and combined IL-28B polymorphisms in HCV-infected Polish
population. OBJECTIVES: This study's aim was to determine predictability of three
IL-28B gene polymorphisms and other known prognostic factors on the treatment
response in HCV genotype 1 and 4 infected Polish patients. The effect of IL-28B
polymorphisms on therapy was also compared with other known prognostic factors.
PATIENTS AND METHODS: We genotyped IL-28B polymorphisms (rs12979860, rs12980275
and rs8099917) by polymerase chain reaction-based restriction fragment length
polymorphism assay in a group of 293 patients from which a selected cohort of 174
treatment-naiev patients underwent treatment. RESULTS: We showed that rs12979860
CC [odds ratio (OR) = 4.6, P < 0.001], rs12980275 AA (OR = 2.9, P = 0.002) and
rs8099917 TT (OR = 2.2, P = 0.016) genotypes were associated with successful
treatment compared to the rs12979860 CT-TT, rs12980275 AG-GG and rs8099917 TG-GG,
respectively. Patients bearing of IL-28B profile including the three favourable
genotypes do not have much chance of a recovery (OR = 3.4, P = 0.002). Except for
IL-28B polymorphisms, there was no association of SVR with any other pretreatment
clinical data in analyzed group. The correlation of SNPs with other host and
viral factors revealed association of favorable genotypes of IL-28B markers with
high levels of alanine aminotransferase and baseline HCV viral load. CONCLUSIONS:
IL-28B polymorphisms were the strongest pretreatment predictors of response to
pegylated interferon and ribavirin in Polish patients chronically infected with
HCV genotype 1 and 4. This study confirm the strongest impact of IL-28B
rs12979860 on SVR, nevertheless rs12980275 AA seems to be more important than
rs8099917 TT in predicting positive treatment response.
PMID- 24348649
TI - A Better Quality of Life in Hemodialysis Patients With Viral Hepatitis: Is it a
Reality?
PMID- 24348650
TI - An Evaluation of Dentin's Effect on the Antifungal Activity of MTA Cements.
AB - INTRODUCTION: The aim of this study was to evaluate the effect of dentin on the
antifungal activity of gray and white-colored MTA (GMTA, WMTA) using a tube
dilution test. MATERIALS AND METHODS: MTA preparations were tested freshly mixed
and after 24h on Candida Albicans (CA). The experiment was performed in 24-well
culture plates. Fifty wells were used and divided into four experimental groups
(freshly-mixed WMTA, freshly-mixed WMTA plus dentin powder, freshly-mixed GMTA,
and freshly-mixed GMTA plus dentin powder) of 10 wells each and control groups of
five wells each. Plates of Sabouraud dextrose agar mixed with CA served as
positive control and Sabouraud dextrose agar without CA served as negative
control. Fresh inoculate of CA was prepared by growing an overnight culture from
a stock culture. Aliquots of CA were then taken from the stock culture and plated
on the agar compound of the experimental and positive control group. All plates
were incubated at 37 degrees C for1h, 24h, and 72h. Growth of fungi was monitored
daily by the presence of turbidity. Kruskal-Wallis test was used for statistical
analysis. RESULTS: Results showed the inhibitory effect of dentin powder on the
antifungal effect of MTA cements during 24h and 72h incubation periods, whereas,
there was no significant difference between 1h incubation groups. CONCLUSION: The
antifungal effect of freshly mixed MTA cements was decreased in the presence of
dentin.
PMID- 24348651
TI - SEM Study of Root Canal Walls Cleanliness after Ni-Ti Rotary and Hand
Instrumentation.
AB - INTRODUCTION: To compare the cleaning effectiveness of K3 and Race NiTi rotary
systems with K-Flexo file instruments during the preparation of curved canals in
extracted human teeth. MATERIALS AND METHODS: A total of 50 root canals of
mandibular and maxillary molars with curvatures ranging between 25o and 35 o were
divided in three groups of 15 each and 5 as negative control groups. Canals were
prepared using a low torque control motor in two rotary groups according to
manufacturer's instructions. Conventional Step back with S.S K files was the
preparation technique in third group. The amount of debris and smear layer was
quantified on the basis of a numerical evaluation scale. The data were
statistically analyzed using Chi-Square and Likelihood Ratio tests. RESULTS: In
general, no significant difference in terms of amount of debris were found among
three groups, only in apical zones of Race and K-Flexo file groups a significant
difference was detected (P=0.041). Race rotary system left significantly less
smear layer than k-Flexo file in the middle (P=0.009) and apical thirds
(P=0.012), respectively. K3 significantly achieved higher scores of cleanliness
than K-Flexo file in apical third only (P=0.049). No significant difference
between Race and K3 rotary groups for residual debris and formed smear layer was
detected. CONCLUSION: Obtaining higher scores of cleanliness in various regions
of the canals, crown down technique and the use of rotary instrumentation seem to
be superior to conventional hand instrumentation with step back technique .No
significant difference between K3 with three radial lands and Race with three
cutting edges in terms of debris and smear layer formation was detected.
PMID- 24348652
TI - An in-vitro evaluation of sealing ability of real seal using fluid filtration.
AB - INTRODUCTION: The aim of this study was to compare the sealing ability of Real
Seal (RS) and Gutta-percha (GP). MATERIALS AND METHODS: Forty nine extracted
human maxillary central incisors were used. The coronal part of each tooth was
removed, the root canal was prepared using the crown down technique and apical
enlargement to rotary file # 40. The specimens were randomly divided in to 3
groups of 15 each and two control groups of 2 each. Group 1, was obturated with
RS and group 2 and 3 were obturated with GP and AH26 sealer by lateral
condensation technique. In group 1 and 3 the smear layer was removed by 5mL of
5.25% NaOCl and 3mL of 17% EDTA. Leakage of the obturated roots was measured
using the fluid filtration technique. This method was done at 2 min intervals for
8 min. data were analyzed using ANOVA and Tukey tests. RESULTS: Statistical
analysis indicated significant differences between groups 2 with 1 and 3. The
most leakage value was observed in the group 2. CONCLUSION: Root canal filling
with RS or GP in combination with smear layer removal showed better sealing.
Therefore the smear layer has more effect one apical leakage than the obturation
system.
PMID- 24348653
TI - Pattern of Antibiotic Prescription among Dentists in Iran.
AB - INTRODUCTION: This study examines the antibiotic prescription in dentists
participated in 9(th) Congress of Iranian Association of Endodontists in
Esfahan/2006. MATERIALS AND METHODS: A questionnaire for this cross sectional
study was designed for evaluating the patterns of antibiotic prescription. It
included some demographic information, clinical signs, and conditions in need for
antibiotic and prophylactic prescription and their choices. Data was analyzed
using Pearson's Chi-square test. RESULTS: High percentage of responders prescribe
antibiotic for fever (78.2%) and diffuse swelling (85.1%). However, some
situations such as acute pulpitis, chronic periapical lesions and marginal
gingivitis were irrationally prescribed. CONCLUSION: This study showed a fairly
good pattern of antibiotic prescription but it was far from ideal.
PMID- 24348654
TI - Presence of Candida Albicans in Root Canal System of Teeth Requiring Endodontic
Retreatment with and without Periapical Lesions.
AB - INTRODUCTION: An important consideration in endodontic treatment is the
elimination of microorganisms, including fungi, from the complex three-
dimensional root canal system. Candida Albicans (CA) has a major role in
endodontic treatment failure as the most important fungus isolated from the root
canal system. The present study was carried out to evaluate the presence of CA in
the teeth requiring endodontic retreatment, with or without periapical lesions.
MATERIALS AND METHODS: This study was carried out on 60 root canals from human
molars requiring endodontic retreatment. The root canals were randomly divided
into two equal groups of 30 canals with versus without periapical lesions.
Samples were collected from the root canals and cultured on MacConkey and blood
agar culture media. The samples suspected of having CA were streaked on
Sabouraud's Dextrose Agar (SDA) and evaluated under a light microscope. Data was
analyzed and compared using Chi- square and Kappa tests. RESULTS: CA was found in
11 patients (36.7%) with periapical lesions. In the patients without periapical
lesions only 4 samples demonstrated CA in the root canal systems (13.3%). The
difference between the two groups as to the presence of CA was statistically
significant (p<0.037). In addition, evaluation of salivary samples revealed 15
cases (50%) of CA presence in the patients with periapical lesions and 16 cases
(53.3%) of CA in the patients without periapical lesions, demonstrating no
statistically significant difference between the two groups. CONCLUSION:
Considering the fact that the presence of CA in the root canal systems of teeth
with periapical lesions was more noticeable and statistically significant
compared to the teeth without periapical lesions, the elimination of this
microorganism from the root canal system, using appropriate intracanal solutions
and medications is of utmost importance.
PMID- 24348655
TI - Analysis of anxiety scale and related elements in endodontic patients.
AB - INTRODUCTION: Anxiety of patients is one of the problems in dentistry which are
considered in recent years, and it prevents them from having a treatment out of
stress. This study was conducted to specify anxiety prevalence and related
elements among endodontic patients. MATERIALS AND METHODS: The study was
conducted on 150 patients referred to Endodontic department of dental school of
Islamic Azad University, using a cross sectional descriptive method in 2006.
Using background characteristics, the patients were classified as a matter of
age, sex, education and related factors such as previous dental visit,
unfavorable experience in dental office, and the most prevalent cause of
referring to dentist. In this regard, Dental Fear Survey (DFS), questionnaire was
used and patients were divided in three groups of anxiety level. The results were
analyzed using Chi-square and Fisher exact tests. RESULTS: The findings showed
highest anxiety scales among dental office referents were statistically
significant for age group of 20-30, women, and under diploma education (P<0.05).
CONCLUSION: Improving the knowledge about causes of anxiety and its preventive
methods are suggested to dentists. They should also provide treatments without
annoyance and trauma.
PMID- 24348656
TI - Maturogenesis of a complicated crown fracture: a case report with 8 years follow
up.
AB - This report describes a case of a 7 years old girl who suffered from complicated
crown fracture of right mandibular central incisor because of a bicycle accident.
For the tooth partial pulpotomy with calcium hydroxide, capping was performed in
order to achieve apexogenesis and the tooth was restored with a double-seal of
glass ionomer cement and composite resin. The patient was reviewed over 8 years.
The tooth showed continued root development and complete apex formation.
PMID- 24348657
TI - The promotion of mental health and the prevention of mental health problems in
child and adolescent.
AB - Improving mental health and reducing the burden of mental illness are
complementary strategies which, along with the treatment and rehabilitation of
people with mental disorders, significantly improve population health and well
being. A Institute of Medicine report describes a range of interventions for
mental disorders that included treatment and maintenance, reserving the term
"prevention" for efforts that occur before onset of a diagnosable disorder.
Mental health problems affect 10-20% of children and adolescents worldwide.
Despite their relevance as a leading cause of health-related disability and their
long lasting consequences, the mental health needs of children and adolescents
are neglected. Early intervention can help reduce the significant impacts that
children and adolescents with serious mental health problems may experience.
Screening is the first step in early intervention, recognizing emotional and
behavioral problems and providing help at an early stage. It is essential to
implement early intervention in a sensitive and ethical manner to avoid any of
the negative outcomes.
PMID- 24348659
TI - Ureaplasma urealyticum or Ureaplasma parvum: what's the difference?
PMID- 24348658
TI - Prevalence of rotavirus genotypes in South Korea in 1989-2009: implications for a
nationwide rotavirus vaccine program.
AB - The epidemiology of human group A rotavirus was analyzed by examining genotypic
data acquired from 1989 to 2009 in South Korea. This information was derived from
all the available published articles on rotavirus studies in South Korea,
retrieved from both the PubMed and KoreaMed databases. Four common G types (G1,
G2, G3, and G4) and three common P types (P[8], P[4], and P[6]) accounted for
approximately 93% and 99% of the rotavirus reports, respectively. The G9 type was
frequently detected after 2000, and because of this prevalence, it is considered
to be the fifth most important G type rotavirus after the G1.G4 genotypes. Less
common G types of the virus such as G12, G11, and G10 were detected in some
geographic settings, and it is important to consider the context of these
subtypes and their epidemiological significance. The P[9] virus genotype was
observed in the study and has been discussed in many other studies; however, the
P[3], P[10] and P[25] genotypes were rarely detected in the epidemiological
research. In general, the distributions of the G and P genotypes showed temporal
and geographical fluctuations, and a nationwide rotavirus vaccine program that
targeted these genotypes demonstrated effectiveness in protecting against the
circulating rotavirus strains. However, further analysis is needed to determine
the true long-term effectiveness of these vaccines; the analysis should also
consider the unexpected effects of vaccinations, such as vaccine-induced
diseases, herd immunity, and changes in host susceptibilities.
PMID- 24348660
TI - Serological investigation of Ureaplasma urealyticum in Korean preterm infants.
AB - PURPOSE: Ureaplasma colonization is related with perinatal complications in
preterm infants. Little is known about the difference in virulence among various
Ureaplasma urealyticum serovars. The aim of this study was to determine U.
urealyticum serovars of preterm infants in order to assess whether any of the
serovars were associated with bronchopulmonary dysplasia (BPD). METHODS: Three
hundred forty-four preterm infants with a gestational age less than 34 weeks
admitted to Gangnam Severance Hospital neonatal intensive care unit from July
2011 to December 2012 were included in this study. Tracheal and gastric
aspirations were conducted on infants to confirm Ureaplasma colonization.
Ureaplasma colonization was confirmed in 9% of infants, of these, serovars were
determined by real-time polymerase chain reaction. RESULTS: A total of 31 infants
(gestational age, 29.3+/-3.1 weeks; birth weight, 1,170+/-790 g) were U.
urealyticum positive. The Ureaplasma positive group treated for more days with
oxygen and ventilation than the negative group (P<0.05). Histologic
chorioamnionitis and moderate to severe BPD were more frequent in the Ureaplasma
positive group than in the negative group (P<0.05). U. urealyticum isolates were
either found to be a mixture of multiple serovars (32%), serovar 9 alone or
combined with other serovars (39%), serovar 11 (26%), 2 (13%), 8 (10%), 10 (13%),
and 13 (25%). No individual serovars were significantly associated with moderate
to severe BPD and chorioamnionitis. CONCLUSION: This is the first study to
describe the distribution of U. urealyticum serovars from Korean preterm infants.
Ureaplasma-colonized infants showed higher incidence of BPD and chorioamnionitis.
PMID- 24348661
TI - The effect of rhinovirus on airway inflammation in a murine asthma model.
AB - PURPOSE: The aim of the present study was to investigate the differences in lower
airway inflammatory immune responses, including cellular responses and responses
in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the
airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a
control and a murine asthma model, with or without RV infection. METHODS: BALB/c
mice were intraperitoneally injected with a crude extract of Dermatophagoides
farinae (Df) or phosphate buffered saline (PBS) and were subsequently
intranasally treated with a crude extract of Df or PBS. Airway responsiveness and
cell infiltration, differential cell counts in BALF, and cytokine and chemokine
concentrations in BALF were measured 24 hours after intranasal RV1B infection.
RESULTS: RV infection increased the enhanced pause (Penh) in both the Df
sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice)
(P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection
(P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and
regulated on activation, normal T cells expressed and secreted (RANTES) increased
in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level
of IL-10 significantly decreased following RV infection in Df mice (P<0.05).
CONCLUSION: Our findings suggest that the augmented induction of proinflammatory
cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and
the decreased induction of regulatory cytokines after RV infection may be
important manifestations leading to airway inflammation with eosinophil
infiltration and changes in airway responsiveness in the asthma model.
PMID- 24348662
TI - Evaluation of risk for graft-versus-host disease in children who receive less
than the full doses of mini-dose methotrexate for graft-versus-host disease
prophylaxis in allogeneic hematopoietic stem cell transplantation.
AB - PURPOSE: The use of cyclosporine and mini-dose methotrexate (MTX) is a common
strategy for graft-versus-host disease (GVHD) prophylaxis in allogeneic
transplants. We investigated whether patients who receive fewer than the planned
MTX doses are at increased risk for GVHD. METHODS: The study cohort included 103
patients who received allogeneic transplants at the Department of Pediatrics of
The Catholic University of Korea College of Medicine, from January 2010 to
December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a
dose of 5 mg/m(2) each. Within the cohort, 76 patients (74%) received all 4 doses
of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3)
group]. RESULTS: Although there was no difference in neutrophil engraftment
between the 2 groups, platelet engraftment was significantly faster in the MTX(4)
group (median, 15 days), compared to the MTX(0-3) group (median, 25 days;
P=0.034). The incidence of grades II-IV acute GVHD was not different between the
MTX(4) and MTX(0-3) groups (P=0.417). In the multivariate study, human leukocyte
antigen mismatch was the most significant factor causing grades II-IV acute GVHD
(P=0.002), followed by female donor to male recipient transplant (P=0.034). No
difference was found between the MTX(4) and MTX (0-3) groups regarding grades III
IV acute GVHD, chronic GVHD, and disease-free survival. CONCLUSION: Our results
indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis
do not lead to increased incidence of either acute or chronic GVHD.
PMID- 24348663
TI - Liver abscess due to Klebsiella pneumoniae in a healthy 12-year-old boy.
AB - Pyogenic liver abscess (PLA) is rare in healthy children. We report a case of PLA
in an immunocompetent 12-year-old boy. Percutaneous catheter drainage was
performed for the abscess. In addition, parenteral antibiotics were administered
for 3 weeks. Klebsiella pneumoniae was detected in the culture of blood and
drained fluid. Here, we present this case and a brief review of the literature on
this subject.
PMID- 24348664
TI - Stroke after percutaneous transhepatic variceal obliteration of esophageal varix
in Caroli syndrome.
AB - Here we present the case of an 11-year-old female patient diagnosed with Caroli
syndrome, who had refractory esophageal varices. The patient had a history of
recurrent bleeding from esophageal varices, which was treated with endoscopic
variceal ligation thrice over a period of 2 years. However, the bleeding was not
controlled. When the patient finally visited the Emergency Department, the
hemoglobin level was 4.4 g/dL. Transhepatic intrajugular portosystemic shunt was
unsuccessful. Subsequently, the patient underwent percutaneous transhepatic
variceal obliteration. Twenty hours after this procedure, the patient complained
of aphasia, dizziness, headache, and general weakness. Six hours later, the
patient became drowsy and unresponsive to painful stimuli. Lipiodol particles
used to embolize the coronary and posterior gastric veins might have passed into
the systemic arterial circulation, and they were found to be lodged in the brain,
kidney, lung, and stomach. There was no abnormality of the portal vein on portal
venography, and blood flow to the azygos vein through the paravertebral and
hemiazygos systems was found to drain to the systemic circulation on coronary
venography. Contrast echocardiography showed no pulmonary arteriovenous fistula.
Symptoms improved with conservative management, and the esophageal varices were
found to have improved on esophagogastroduodenoscopy.
PMID- 24348665
TI - Biopsy and mutation detection strategies in non-small cell lung cancer.
AB - The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC)
implies that histologic subtyping and molecular predictive testing are now
essential for therapeutic decisions. Histologic subtype predicts the efficacy and
toxicity of some treatment agents, as do genetic alterations, which can be
important predictive factors in treatment selection. Molecular markers, such as
epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase
(ALK) rearrangement, are the best predictors of response to specific tyrosine
kinase inhibitor treatment agents. As the majority of patients with NSCLC present
with unresectable disease, it is therefore crucial to optimize the use of tissue
samples for diagnostic and predictive examinations, particularly for small biopsy
and cytology specimens. Therefore, each institution needs to develop a diagnostic
approach requiring close communication between the pulmonologist, radiologist,
pathologist, and oncologist in order to preserve sufficient biopsy materials for
molecular analysis as well as to ensure rapid diagnosis. Currently, personalized
medicine in NSCLC is based on the histologic subtype and molecular status. This
review summarizes strategies for tissue acquisition, histologic subtyping and
molecular analysis for predictive testing in NSCLC.
PMID- 24348666
TI - Molecular basis of drug resistance: epidermal growth factor receptor tyrosine
kinase inhibitors and anaplastic lymphoma kinase inhibitors.
AB - Over the past decade, several kinase inhibitors have been approved based on their
clinical benefit in cancer patients. Unfortunately, in many cases, patients
develop resistance to these agents via secondary mutations and alternative
mechanisms. To date, several major mechanisms of acquired resistance, such as
secondary mutation of the epidermal growth factor receptor (EGFR) gene,
amplification of the MET gene and overexpression of hepatocyte growth factor,
have been reported. This review describes the recent findings on the mechanisms
of primary and acquired resistance to EGFR tyrosine kinase inhibitors and
acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing
on non-small cell lung carcinoma.
PMID- 24348667
TI - Increasing Recovery of Nontuberculous Mycobacteria from Respiratory Specimens
over a 10-Year Period in a Tertiary Referral Hospital in South Korea.
AB - BACKGROUND: The number of patients with pulmonary disease caused by
nontuberculous mycobacteria (NTM) has been increasing worldwide. The aim of this
study was to evaluate long-term trends in the NTM recovery rate from respiratory
specimens over a 10-year period in a tertiary referral hospital in South Korea.
METHODS: We retrospectively reviewed the records of mycobacterial cultures of
respiratory specimens at Samsung Medical Center from January 2001 to December
2011. RESULTS: During the study period, 32,841 respiratory specimens from 10,563
patients were found to be culture-positive for mycobacteria. These included
12,619 (38%) Mycobacterium tuberculosis and 20,222 (62%) NTM isolates. The
proportion of NTM among all positive mycobacterial cultures increased from 43%
(548/1,283) in 2001 to 70% (3,341/4,800) in 2011 (p<0.001, test for trend). The
recovery rate of NTM isolates from acid-fast bacilli smear-positive specimens
increased from 9% (38/417) in 2001 to 64% (1,284/1,997) in 2011 (p<0.001, test
for trend). The proportion of positive liquid cultures was higher for NTM than
for M. tuberculosis (p<0.001). The most frequently isolated NTM were
Mycobacterium avium-intracellulare complex (53%) and Mycobacterium abscessus
massiliense complex (25%). CONCLUSION: The recovery rate of NTM from respiratory
specimens in South Korea has increased steadily.
PMID- 24348668
TI - Effect of Prunetin on TNF-alpha-Induced MUC5AC Mucin Gene Expression, Production,
Degradation of IkappaB and Translocation of NF-kappaB p65 in Human Airway
Epithelial Cells.
AB - BACKGROUND: We investigated whether prunetin significantly affects tumor necrosis
factor-alpha (TNF-alpha)-induced MUC5AC mucin gene expression, production,
inhibitory kappa B (IkappaB) degradation and nuclear factor kappa B (NF-kappaB)
p65 translocation in human airway epithelial cells. METHODS: Confluent NCI-H292
cells were pretreated with prunetin for 30 minutes and then stimulated with TNF
alpha for 24 hours or the indicated periods. MUC5AC mucin gene expression and
mucin protein production were measured by reverse transcription polymerase chain
reaction and enzyme-linked immunosorbent assay, respectively. The effect of
prunetin on TNF-alpha-induced degradation of IkappaB and translocation of NF
kappaB p65 was investigated by western blot analysis. RESULTS: We found that
incubation of NCI-H292 cells with prunetin significantly inhibited mucin
production and down-regulated the MUC5AC gene expression induced by TNF-alpha.
Prunetin inhibited TNF-alpha-induced degradation of IkappaB and translocation of
NF-kappaB p65. CONCLUSION: This result suggests that prunetin inhibits the NF
kappaB signaling pathway, which may explain its role in the inhibition of MUC5AC
mucin gene expression and production regulated by the NF-kappaB signaling
pathway.
PMID- 24348669
TI - An unusual case of superior vena cava syndrome caused by the intravascular
invasion of an invasive thymoma.
AB - Superior vena cava syndrome (SVCS) is usually caused by extrinsic compression or
invasion of the superior vena cava (SVC) by malignant tumors involving
mediastinal structures. Although thymomas are well-known causes of SVCS, cases of
SVCS caused by malignant thymomas protruding into adjacent vessels draining the
SVC with thrombosis have been very rarely reported worldwide. We experienced a 39
year-old female patient with SVCS that developed after the direct invasion of the
left brachiocephalic vein (LBCV) and SVC by an anterior mediastinal mass with a
high maximum standardized uptake value on the chest computed tomography (CT) and
positron emission tomography-CT. Based on these results, she underwent en bloc
resection of the tumor, including removal of the involved vessels, and was
eventually diagnosed as having a type B2 thymoma permeating into the LBCV and
SVC. We present this case as a very rare form of SVCS caused by an invasive
thymoma.
PMID- 24348670
TI - Spontaneous regression of non-small cell lung cancer in a patient with idiopathic
pulmonary fibrosis: a case report.
AB - Treatment of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is
difficult because the mortality rate after surgery or chemotherapy is high for
these patients. Spontaneous regression of cancer is rare, especially in lung
cancer. A 62-year-old man, previously diagnosed with IPF, presented with stage
IIIC (T2N3M0) non-small cell lung cancer. About 4 months later, spontaneous
regression of the primary tumor was observed without treatment. To the best of
our knowledge, this is the first report of spontaneous regression of lung cancer
in a patient with IPF.
PMID- 24348671
TI - Spontaneous Splenic Rupture as a Paradoxical Reaction during Treatment for
Splenic Tuberculosis.
AB - This report describes a rare case of a patient with splenic tuberculosis (TB) who
developed spontaneous splenic rupture after 10 weeks of antituberculous
chemotherapy. The patient responded well to the antituberculous regimen prior to
the spontaneous splenic rupture. We considered a paradoxical reaction as a cause
of the splenic rupture. The patient underwent splenectomy and continuously
received initial antituberculous drugs without change. To the best of our
knowledge, this is the first report of spontaneous splenic rupture as a
paradoxical reaction to antituberculous chemotherapy in an immunocompetent host
with splenic TB.
PMID- 24348672
TI - A case of bilateral giant bullae in young adult.
AB - Giant bullae are large bullae occupying at least one-third of the hemithorax and
surgical bullectomy is the treatment of choice. We report a case with symptomatic
giant bullae which were resected successfully. A 35-year-old man presented with
bilateral giant bullae that occupied almost the entire left hemithorax and a
third of the right hemithorax. He was a current smoker with a 30 pack-year
history and he presented with dyspnea on exertion. An elective surgical
bullectomy was performed with video-assisted thoracoscopic surgery. The patient
recovered without any adverse events and stayed well for 1 month after surgery.
PMID- 24348673
TI - Haemophilus parasuis subunit vaccines based on native proteins with affinity to
porcine transferrin prevent the expression of proinflammatory chemokines and
cytokines in pigs.
AB - The expression of chemokines (CCL-2 and CXCL-8) and cytokines (IL-1 alpha , IL-1
beta , IL-6, TNF- alpha , and IL-10) was evaluated by RT-qPCR in colostrum
deprived pigs vaccinated and challenged with Haemophilus parasuis serovar 5. Two
vaccines containing native proteins with affinity to porcine transferrin (NPAPTim
and NPAPTit) were tested, along with two control groups: one inoculated with PBS
instead of antigen (challenge group (CHG)), and another one nonimmunized and
noninfected (blank group). The use of NPAPTim and NPAPTit resulted in complete
protection against H. parasuis (no clinical signs and/or lesions), and both
vaccines were capable of avoiding the expression of the proinflammatory molecules
to levels similar to physiological values in blank group. However, overexpression
of all proinflammatory molecules was observed in CHG group, mainly in the target
infection tissues (brain, lungs, and spleen). High expression of CCL-2, CXCL-8,
IL-1 alpha , IL-1 beta , and IL-6 can be considered one of the characteristics of
H. parasuis infection by serovar 5.
PMID- 24348674
TI - Modulatory effect of 1,25-dihydroxyvitamin D 3 on IL1 beta -induced RANKL, OPG,
TNF alpha , and IL-6 expression in human rheumatoid synoviocyte MH7A.
AB - Receptor activator of nuclear factor kappa B ligand (RANKL) plays a crucial role
in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis.
Considering that 1,25(OH)2D3 has been suggested as a potent inducer of RANKL
expression, it should clarify whether vitamin D supplement could result in RANKL
overexpression and thereby facilitate excessive osteoclastogenesis and bone
resorption in RA. Here, we investigated modulatory effect of 1,25(OH)2D3 on the
expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an
inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were
stimulated with IL1 beta and then treated with different concentrations of
1,25(OH)2D3 for 48 h. A significantly elevated OPG/RANKL ratio and markedly
decreased levels of IL-6 and TNF beta mRNA expression in cells and IL-6 protein
in supernatants were observed in IL1 beta -induced MH7A in the presence of
1,25(OH)2D3 compared with those in the absence of it. Osteoclast formation was
obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3 and
IL1 beta . In summary, although it has a biological function to induce RANKL
expression, 1,25(OH)2D3 could upregulate OPG/RANKL ratio and mediate anti
inflammatory action in an inflammatory milieu of synoviocyte, contributing to the
inhibition of inflammation-induced osteoclastogenesis in RA.
PMID- 24348675
TI - Effect of selective serotonin reuptake inhibitors and immunomodulator on
cytokines levels: an alternative therapy for patients with major depressive
disorder.
AB - Major depressive disorder (MDD) is a psychiatric illness that presents as a
deficit of serotonergic neurotransmission in the central nervous system. MDD
patients also experience alterations in cortisol and cytokines levels. Treatment
with selective serotonin reuptake inhibitors (SSRIs) is the first-line
antidepressant regimen for MDD. The aim of this study was to determine the effect
of a combination of SSRIs and an immunomodulator-human dialyzable leukocyte
extract (hDLE)-on cortisol and cytokines levels. Patients received SSRIs or SSRIs
plus hDLE. The proinflammatory cytokines IL-1 beta , IL-2, and IFN- gamma ; anti
inflammatory cytokines IL-13 and IL-10; and 24-h urine cortisol were measured at
weeks (W) 0, 5, 20, 36, and 52 of treatment. The reduction in cortisol levels in
the SSRI-treated group was 30% until W52, in contrast, the combined treatment
induced a 54% decrease at W36. The decline in cortisol in patients who were
treated with SSRI plus hDLE correlated with reduction of anti-inflammatory
cytokines and increases levels of proinflammatory cytokines at the study
conclusion. These results suggest that the immune-stimulating activity of hDLE,
in combination with SSRIs, restored the pro- and anti-inflammatory cytokine
balance and cortisol levels in depressed patients versus those who were given
SSRIs alone.
PMID- 24348676
TI - Decreased CD127 expression on CD4+ T-cells and elevated frequencies of
CD4+CD25+CD127- T-cells in children with long-lasting type 1 diabetes.
AB - Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell
related actions. Homeostasis of majority of T-cells is critically dependent on
signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast,
regulatory T-cells express very little CD127 and thereby may be delineated by
CD4+CD25+CD127- phenotype. Here we aimed to analyze CD127 expression on CD4+ and
CD8+ T-cells and enumerate CD4+CD25+CD127- T-cells in long-lasting T1D. T-cells
were analyzed by flow cytometry and immunologic data were correlated with
vascular, metabolic, and inflammatory parameters. We demonstrated significantly
decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients.
Interestingly, frequencies of CD4+CD25+CD127- T-cells were significantly enhanced
in T1D children and correlated well with frequencies of CD34+CD144+ endothelial
progenitor cells and CD4+CD25- T-cells. Levels of CD127 on both CD4+ and CD8+ T
cells in T1D patients were not correlated to each other or HbA1C. Interestingly,
however, CD127 levels on CD4+ T-cells were significantly correlated to
frequencies of CD4+CD25+CD127- T-cells, whereas CD127 levels on CD8+ T-cells were
significantly correlated to concentrations of VEGF and triglycerides. Our data
indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T
cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent
onset T1D, long-lasting T1D is associated with enhancement of T-cells with
regulatory phenotype.
PMID- 24348677
TI - Selection of conserved epitopes from hepatitis C virus for pan-populational
stimulation of T-cell responses.
AB - The hepatitis C virus (HCV) is able to persist as a chronic infection, which can
lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is
linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that
eliciting CTL responses against HCV through an epitope-based vaccine could prove
an effective means of immunization. However, HCV genomic plasticity as well as
the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges
the selection of epitopes for a widely protective vaccine. Here, we devised an
approach to overcome these limitations. From available databases, we first
collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted
in the course of a natural infection in humans. After a sequence variability
analysis, we next identified 17 highly invariant epitopes. Subsequently, we
predicted the epitope HLA I binding profiles that determine their potential
presentation and recognition. Finally, using the relevant HLA I-genetic
frequencies, we identified various epitope subsets encompassing 6 conserved HCV
specific CTL epitopes each predicted to elicit an effective T-cell response in
any individual regardless of their HLA I background. We implemented this epitope
selection approach for free public use at the EPISOPT web server.
PMID- 24348678
TI - Modulation of LPS-induced CD4+ T-cell activation and apoptosis by antioxidants in
untreated asymptomatic HIV infected participants: an in vitro study.
AB - Persistent immune activation characterises HIV infection and is associated with
depletion of CD4+ T-cells and increased risk of disease progression. Early loss
of gut mucosal integrity results in the translocation of microbial products such
as lipopolysaccharide (LPS) into the systemic circulation. This is an important
source of on-going immune stimulation. The purpose of this study was to determine
levels of CD4+ T-cell activation (%CD25 expression) and apoptosis (% annexin V/7
AAD) in asymptomatic, untreated HIV infection at baseline and after stimulation
with LPS and incubation with or without vitamin C and N-acetylcysteine. LPS
induced a significant (P < 0.03) increase in %CD25 expression, annexin V, and 7
AAD in HIV positive individuals. NAC in combination with vitamin C, significantly
(P = 0.0018) reduced activation and early apoptosis of CD4+ T-cells to a greater
degree than with either antioxidant alone. Certain combinations of antioxidants
could be important in reducing the harmful effects of chronic immune activation
and thereby limit CD4+ T-cell depletion. Importantly, we showed that CD4+ T-cells
of the HIV positive group responded better to a combination of the antioxidants
at this stage than those of the controls. Therefore, appropriate intervention at
this asymptomatic stage could rescue the cells before repetitive activation
results in the death of CD4+ T-cells.
PMID- 24348679
TI - Impaired lymphocyte profile in schistosomiasis patients with periportal fibrosis.
AB - The Th2 immune response in chronic schistosomiasis is associated with the
development of periportal fibrosis. However, little is known about the phenotype
and activation status of T cells in the process. Objective. To evaluate the
profile of T cells in schistosomiasis patients with periportal fibrosis. Methods.
It was a cross-sectional study, conducted in the village of Agua Preta, Bahia,
Brazil, which included 37 subjects with periportal fibrosis determined by
ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol
hypaque gradient and the frequency of T cells expressing the surface markers
CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The
frequency of CD4(+)CD28(+) T lymphocytes was higher in individuals with moderate
to severe fibrosis compared to patients with incipient fibrosis. We did not
observe any significant difference in the frequency of CD4(+) T cells expressing
CD69 among groups of individuals. There was also no significant difference in the
frequency of CD8(+) T cells expressing CD28 or CD69 among the studied groups.
Individuals with moderate to severe fibrosis presented a lower frequency of
CD8(+) T cells, CD4(+)CD25(high) T cells, and CD4(+)CTLA-4(+) T cells when
compared to patients without fibrosis or incipient fibrosis. The frequency of
CD4(+)CD25(low) cells did not differ between groups. Conclusion. The high
frequency of activated T cells coinciding with a low frequency of putative Treg
cells may account for the development of periportal fibrosis in human
schistosomiasis.
PMID- 24348680
TI - Interferon alpha association with neuromyelitis optica.
AB - Interferon-alpha (IFN- alpha ) has immunoregulatory functions in autoimmune
inflammatory diseases. The goal of this study was to determine occurrence and
clinical consequences of IFN- alpha in neuromyelitis optica (NMO) patients.
Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population-based
retrospective case series were included. Expanded Disability Status Scale (EDSS)
score and MRI findings determined disease activity. Linear regression was used to
assess the effects of the level of IFN- alpha on disability (EDSS). IFN- alpha
was determined by sensitive ELISA assays. IFN- alpha was detectable in sera from
9/36 NMO patients, significantly more often than in the MS group (2/41) (P =
0.0197). A higher frequency of IFN- alpha was observed in NMO patients with acute
relapse compared to NMO patients in remission (P < 0.001) and compared to the MS
patients with relapse (P = 0.010). In NMO patients, the levels of IFN- alpha were
significantly associated with EDSS (P = 0.0062). It may be concluded that IFN-
alpha was detectable in a subgroup of NMO patients. Association of IFN- alpha
levels with clinical disease activity and severity suggests a role for IFN- alpha
in disease perpetuation and may provide a plausible explanation for a negative
effect of IFN-1 treatment in NMO patients.
PMID- 24348681
TI - Potential immune modularly role of glycine in oral gingival inflammation.
AB - Gingival epithelial cells (GECs) represent a physical barrier against bacteria
and are involved in the processes of innate immunity. Recently, an anti
inflammatory and immune-modulatory effect of the amino acid glycine has been
demonstrated. However, there is only little information about the immune
modulatory effects of glycine in oral tissues. This study aimed to investigate
the existence and role of the glycine receptor in gingival tissue analyzing
tissues/cells from extracted human molars via immunohistochemical analysis. In
vitro, GECs were challenged by inflammatory conditions with IL-1 beta alone or in
combination with glycine and analyzed for cytokine expression of IL6/IL8 via real
time PCR. On protein level, the effect of nuclear translocalization of NF kappa B
protein p65 was analyzed using immunofluorescence analysis. A distinct proof of
the GlyR in oral gingival tissue and keratinocytes could be demonstrated.
Isolated challenge of the keratinocytes with IL-1 beta as well as with glycine
resulted in an upregulation of IL6 and IL8 mRNA expression and activation of NF
kappa B pathway. The presence of glycine in combination with the inflammatory
stimulus led to a significant decrease in inflammatory parameters. These results
indicate a possible anti-inflammatory role of glycine in gingival inflammation
and encourage further research on the utility of glycine in the prevention or
therapy of inflammatory periodontitis.
PMID- 24348682
TI - APACHE IV is superior to MELD scoring system in predicting prognosis in patients
after orthotopic liver transplantation.
AB - This study aims to compare the efficiency of APACHE IV with that of MELD scoring
system for prediction of the risk of mortality risk after orthotopic liver
transplantation (OLT). A retrospective cohort study was performed based on a
total of 195 patients admitted to the ICU after orthotopic liver transplantation
(OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD
scoring systems were used to predict the postoperative mortality after OLT. The
area under the receiver operating characteristic curve (AUC) and the Hosmer
Lemeshow C statistic were used to assess the discrimination and calibration of
APACHE IV and MELD, respectively. Twenty-seven patients died during
hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and
MELD were 42.32 +/- 21.95 and 18.09 +/- 10.55, respectively, and APACHE IV showed
better discrimination than MELD; the areas under the receiver operating
characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for
both models), which indicated that the prognostic value of APACHE IV was
relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C
statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for
both). The respective Youden indexes of APACHE IV, MELD, and combination of
APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE
IV is high but still underestimates the overall hospital mortality, while the
prognostic value of MELD is poor. The function of the APACHE IV is, thus, better
than that of the MELD.
PMID- 24348683
TI - Incidence and clinical significance of de novo donor specific antibodies after
kidney transplantation.
AB - Kidney transplantation has evolved over more than half a century and remarkable
progress has been made in patient and graft outcomes. Despite these advances,
chronic allograft dysfunction remains a major problem. Among other reasons, de
novo formation of antibodies against donor human leukocyte antigens has been
recognized as one of the major risk factors for reduced allograft survival. The
type of treatment in the presence of donor specific antibodies (DSA)
posttransplantation is largely related to the clinical syndrome the patient
presents with at the time of detection. There is no consensus regarding the
treatment of stable renal transplant recipients with circulating de novo DSA. On
the contrast, in acute or chronic allograft dysfunction transplant centers use
various protocols in order to reduce the amount of circulating DSA and achieve
long-term graft survival. These protocols include removal of the antibodies by
plasmapheresis, intravenous administration of immunoglobulin, or depletion of B
cells with anti-CD20 monoclonal antibodies along with tacrolimus and
mycophenolate mofetil. This review aims at the comprehension of the clinical
correlations of de novo DSA in kidney transplant recipients, assessment of their
prognostic value, and providing insights into the management of these patients.
PMID- 24348684
TI - Tumor protective activity of CD4+ but not of CD8+ T cells in DNA-vaccinated mice
challenged with bcr-abl-transformed cells.
AB - In the recent past, it has repeatedly been reported that CD4 cells play an
important role in the immunology of chronic myeloid leukaemia. It was therefore
of interest to test their activity in an animal model using bcr-abl-transformed
cells. BALB/c mice were four times immunized with a DNA vaccine carrying the bcr
abl fusion gene. Two weeks after the last vaccine dose, the animals were
challenged with syngeneic bcr-abl-transformed 12B1 cells which form solid tumors
after subcutaneous administration. At the time of challenge, animals were treated
with antibodies against the CD8+ T cells or CD4+ T cells. The efficacy of the
depletion was monitored and found highly effective. All nonimmunized animals
developed tumors. All animals untreated with the antibodies as well as those in
which CD8+ T cells had been depleted, were fully protected against the challenge.
On the other hand, almost all mice treated with anti-CD4+ antibody developed
tumors. These results strongly suggested that the CD4+ T cells acted as effectors
in the present system.
PMID- 24348685
TI - TSLP: A Key Regulator of Asthma Pathogenesis.
AB - Asthma is a complex disorder of the airways that is characterized by T helper
type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an
important player involved in orchestrating the inflammation seen in asthma and
other atopic diseases. Early research elucidated the role of TSLP on CD4+ T
cells, and recent work has revealed the impact of TSLP on multiple cell types.
Furthermore, TSLP plays an important role in the sequential progression of atopic
dermatitis to asthma, clarifying the key role of TSLP in the pathogenesis of
asthma, a finding with therapeutic implications.
PMID- 24348686
TI - Premature guidance about whole-genome sequencing.
PMID- 24348687
TI - Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats:
Role of the Dopamine D2 Receptor.
AB - Background. Cerebral ischemia is known to produce brain damage and related
behavioural deficits, including memory deficits and motor disorders. Evidence
shows that EA significantly promotes recovery of neurological function and thus
improves quality of life. Objective. Evidence exists for the involvement of
catecholamines in human neuroplasticity. A better understanding of dopaminergic
(DAergic) modulation in this process will be important. Methods. A total of 72
adult male Sprague-Dawley (SD) rats were divided into 6 groups: normal, model,
EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral
artery occlusion (MCAO) model was used in all 6 groups except the normal group. A
behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The
percent of brain infarct area was also determined 7 days after MCAO. Tyrosine
hydroxylase (TH) and growth-associated protein 43 (GAP-43) fluorescence double
labeling was performed in the striatum. Results. In this study, we found that EA
at Fengchi (GB20) acupoints resulted in marked improvements based on a
behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling
results showed that EA treatment reduced ischemia injury and promoted
neuroplasticity compared with the model group. The D2R-selective agonist,
pergolide, showed similar results, but these results were reversed by the D2R
selective antagonist, spiperone. We also found that there were more
colocalization and expression of GAP-43 and TH in the EA and pergolide groups
than those in the other groups. Conclusion. These results suggest that the
neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic
neurons.
PMID- 24348688
TI - Insoluble fiber in young barley leaf suppresses the increment of postprandial
blood glucose level by increasing the digesta viscosity.
AB - Barley (Hordeum vulgare L.) is a well-known cereal plant. Young barley leaf is
consumed as a popular green-colored drink, which is named "Aojiru" in Japan. We
examined the effects of barley leaf powder (BLP) and insoluble fibers derived
from BLP on postprandial blood glucose in rats and healthy Japanese volunteers.
BLP and insoluble fibers derived from BLP suppressed the increment of
postprandial blood glucose levels in rats (P < 0.01), and increased the viscosity
of their digesta. The insoluble fibers present in BLP might play a role in
controlling blood glucose level by increasing digesta viscosity. In human, BLP
suppressed the increment of postprandial blood glucose level only in those which
exhibited higher blood glucose levels after meals (P < 0.01). BLP might suppress
the increment of postprandial blood glucose level by increasing digesta viscosity
in both of rats and humans who require blood glucose monitoring.
PMID- 24348689
TI - Effect of Nelumbo nucifera Petal Extracts on Lipase, Adipogenesis, Adipolysis,
and Central Receptors of Obesity.
AB - N. nucifera is one among the important medicinal plants assessed for its
antiobesity action in various preclinical models. The present study was aimed at
investigating the antiobesity effect of methanol and successive water extracts of
petals of N. nucifera by studying its effect on adipogenesis, adipolysis, lipase,
serotonin (5-HT2C), cannabinoid (CNR2), melanocyte concentrating hormone (MCHR1),
and melanocortin (MC4R) receptors. Both methanol and successive water extracts of
N. nucifera petals had an effect on inhibition of lipid storage in adipocytes and
on increasing lipolysis. N. nucifera petal methanol extract exhibited the
concentration-dependent inhibitory effect on lipase activity with an IC50 value
of 47 ug/mL. N. nucifera petal extracts showed evident agonist and antagonist
activity towards 5-HT2C and CNR2 receptors, respectively, while it showed no
effect towards MCHR1 and MC4R receptors. Overall, methanol extract of N. nucifera
petals showed better activity than successive water extract.
PMID- 24348690
TI - Anti-Inflammatory Activity of Water-Soluble Polysaccharide of Agaricus blazei
Murill on Ovariectomized Osteopenic Rats.
AB - In the present study, we investigated the anti-inflammatory activity of water
soluble polysaccharide of Agaricus blazei Murill (WSP-AbM) on ovariectomized
osteopenic rats. The rats were administered orally WSP-AbM (200 mg/kg BW) for 8
weeks. Subsequent serum maleic dialdehyde (MDA) level, total antioxidant status
(TAOS), nuclear factor kappa B (NF- kappa B) level, polymorphonuclear (PMN) cells
level, interleukin-1 beta (IL-1 beta ) level, inducible nitric oxide synthase
(iNOS) level, tumor necrosis factor- alpha (TNF- alpha ) level, adhesion molecule
(ICAM-1), and cyclooxygenase-2 (COX-2) were determined by enzyme linked
immunosorbent assay (ELISA) and immunohistochemistry, respectively. WSP-AbM
administration markedly (P < 0.05) decreased serum IL-1 beta and TNF- alpha
levels and the expressions of ICAM-1, COX-2, and iNOS NF- kappa B compared with
OVX rats. WSP-AbM administration alsomarkedly (P < 0.05) decreased PMN
infiltration. In conclusion, we observed that WSP-AbM supplementation had anti
inflammatory effects in a model of osteoporosis disease.
PMID- 24348691
TI - Spiritual needs in patients suffering from fibromyalgia.
AB - The objective of this study was to assess spiritual needs of patients with
fibromyalgia syndrome (FMS) and to evaluate correlations with disease and health
associated variables. Using a set of standardized questionnaires (i.e., Spiritual
Needs Questionnaire, Fibromyalgia Impact Questionnaire, SF-36's Quality of Life,
Brief Multidimensional Life Satisfaction Scale, etc.), we enrolled 141 patients
(95% women, mean age 58 +/- 10 years). Here, needs for inner peace and
giving/generativity scored the highest, while existential needs and religious
needs scored lowest. Particularly inner peace needs and existential needs
correlated with different domains of reduced mental health, particularly with
anxiety, the intention to escape from illness, and psychosocial restrictions.
Thirty-eight percent of the patients stated needs to be forgiven and nearly half
to forgive someone from their past life. Therefore, the specific spiritual needs
of patients with chronic diseases should be addressed in clinical care in order
to identify potential therapeutic avenues to support and stabilize their
psychoemotional situation.
PMID- 24348692
TI - Effect of jeju water on blood glucose levels in diabetic patients: a randomized
controlled trial.
AB - Jeju water is the groundwater of Jeju Island, a volcanic island located in
Republic of Korea. We investigated whether Jeju water improved glycemic control
in patients with diabetes. This was a 12-week single-center, double-blind,
randomized, and controlled trial. The subjects daily drank a liter of one of
three kinds of water: two Jeju waters (S1 and S2) and Seoul tap water (SS). The
primary outcome was the proportion of patients in the per-protocol (PP)
population achieving glycated hemoglobin (HbA1c) < 7.0% at week 12. In total, 196
patients were randomized and analyzed in the intention-to-treat (ITT) population
(66 consuming S1, 63 consuming S2, and 67 consuming SS); 146 patients were
considered in the PP population. There were no significant differences in the
primary outcomes of the groups consuming S1, S2, or SS. However, the percentage
of patients achieving HbA1c < 8% was significantly higher in the S2 group than in
the SS group. In the ITT population, the 12-week HbA1c and fructosamine levels
were lower in the S1 group than in the SS group and the 4-, 8-, and 12-week
fructosamine levels were lower in the S2 group than in the SS group. Although we
failed to achieve the primary outcome, it is possible that the Jeju waters
improve glycemic control compared with the Seoul tap water in diabetic patients.
PMID- 24348693
TI - Bioinformatics analysis for the antirheumatic effects of huang-lian-jie-du-tang
from a network perspective.
AB - Huang-Lian-Jie-Du-Tang (HLJDT) is a classic TCM formula to clear "heat" and
"poison" that exhibits antirheumatic activity. Here we investigated the
therapeutic mechanisms of HLJDT at protein network level using bioinformatics
approach. It was found that HLJDT shares 5 target proteins with 3 types of anti
RA drugs, and several pathways in immune system and bone formation are
significantly regulated by HLJDT's components, suggesting the therapeutic effect
of HLJDT on RA. By defining an antirheumatic effect score to quantitatively
measure the therapeutic effect, we found that the score of each HLJDT's component
is very low, while the whole HLJDT achieves a much higher effect score,
suggesting a synergistic effect of HLJDT achieved by its multiple components
acting on multiple targets. At last, topological analysis on the RA-associated
PPI network was conducted to illustrate key roles of HLJDT's target proteins on
this network. Integrating our findings with TCM theory suggests that HLJDT
targets on hub nodes and main pathway in the Hot ZENG network, and thus it could
be applied as adjuvant treatment for Hot-ZENG-related RA. This study may
facilitate our understanding of antirheumatic effect of HLJDT and it may suggest
new approach for the study of TCM pharmacology.
PMID- 24348694
TI - Manual acupuncture and laser acupuncture for autonomic regulations in rats:
observation on heart rate variability and gastric motility.
AB - This study focused on the effects of laser acupuncture (LA) and manual
acupuncture (MA) at different acupoints on gastric motility and heart rate
variability (HRV) simultaneously to elucidate the site specific effects of
acupoints and the correlation between changes of gastric motility and low
frequency/high frequency (LF/HF) ratio. Gastric motility and HRV were recorded
before and during MA or LA. Stimulating PC-6 or ST-36 significantly enhanced
gastric motility, while BL-21 caused no changes. In contrast, MA or LA at CV-12
significantly suppressed gastric motility. Stimulating PC-6 or ST-36
significantly increased heart rate (HR), while CV-12 or BL-21 induced no
significant changes of HR. Stimulating PC-6 significantly increased LF/HF, while
ST-36, CV-12, or BL-21 induced no significant effects. These results indicated
that there was acupoint specificity in the effects of acupuncture on gastric
motility and HRV. The stimulatory effect of MA and LA at PC-6 and ST-36 on HR was
associated with sympathetic activity. The stimulatory effect of MA or LA at PC-6
or ST-36 on gastric motility was associated with vagal activity. Laser needle can
be used as an alternative stimulation therapy.
PMID- 24348695
TI - German psychiatrists' observation and interpretation of religiosity/spirituality.
AB - The purpose of this study was to explore how contemporary German psychiatrists
think about religiosity/spirituality (ReS) in regard to their therapies. We
conducted an anonymous survey among the clinical staff of psychiatry and
psychotherapy departments in German university hospitals and faith-based clinics
in the same cities. Two main instruments were used, the Duke University Religion
Index (DUREL) and the questionnaire from Curlin et al. "Religion and Spirituality
in Medicine: Physicians' Perspectives." A total of 123 psychiatrists participated
in this survey. However, due to incomplete responses, only 99 questionnaires from
psychiatrists were analyzed. Results show that German psychiatrists positively
experience the influence of ReS on patients' mental health. Psychiatrists' own
ReS significantly influenced their interpretation of the effect of ReS on
psychiatric patients as well as their attitude toward ReS in the clinical
setting. The more religious psychiatrists are, the more they tend to observe a
positive influence of ReS on mental health. In light of these results,
psychiatrists should be aware of their own religious/spiritual characteristics
and also reconsider their assumptions about professional neutrality and value
openness. Furthermore, training programs on religious/spiritual issues and
effective teamwork with chaplains are recommended.
PMID- 24348696
TI - Establishment of an Experimental Breast Cancer ZHENG Model and Curative Effect
Evaluation of Zuo-Jin Wan.
AB - Herbal formulas based on the traditional Chinese medicine (TCM) syndrome (ZHENG)
have been used as alternative treatments for breast cancer. However, there is a
lack of the experimental animal ZHENG model for the evaluation of the herbal
formulas. In this study, we have established 4T1 mouse breast cancer with Liver
Fire Invading Stomach Syndrome model (4T1 LFISS mice) and investigated the
effects of the herbal formula, Zuo-Jin Wan (ZJW). Our results showed that 4T1
LFISS mice have the features of LFISS including irritability, loss of appetite,
yellow urine, chow, and a tail hot. Compared to untreated 4T1 LFISS mice, ZJW
significantly reduced tumor weight and volume (P < 0.05), although it was weaker
than Cisplatin. However, ZJW significantly increased the body weight and food
intake of 4T1 LFISS mice and decreased serum ALT, AST, Cr, and BUN levels and
ZHENG score (P < 0.05), while Cisplatin reduced the food intake, and body weight
and increased serum ALT, AST, Cr, and BUN levels in 4T1 LFISS mice. Our study has
provided a mouse breast cancer ZHENG model and showed that ZJW suppresses tumor
growth and improves LFISS and kidney and liver functions in the 4T1 LFISS mice.
PMID- 24348697
TI - Direct radiofrequency application improves pain and gait in collagenase-induced
acute achilles tendon injury.
AB - Radiofrequency (RF) is often used as a supplementary and alternative method to
alleviate pain for chronic tendinopathy. Whether or how it would work for acute
tendon injury is not addressed in the literatures. Through detailed pain and gait
monitoring, we hypothesized that collagenase-induce acute tendinopathy model may
be able to answer these questions. Gait parameters, including time, distance, and
range of motion, were recorded and analyzed using a walking track equipped with a
video-based system. Expression of substance P (SP), calcitonin gene related
peptide (CGRP), and galanin were used as pain markers. Beta-III tubulin and
Masson trichrome staining were used as to evaluate nerve sprouting, matrix
tension, and degeneration in the tendon. Of fourteen analyzed parameters, RF
significantly improved stance phase, step length, preswing, and intermediary toe
spread of gait. Improved gait related to the expression of substance P, CGRP, and
reduced nerve fiber sprouting and matrix tension, but not galanin. The study
indicates that direct RF application may be a valuable approach to improve gait
and pain in acute tendon injury. Altered gait parameters may be used as
references to evaluate therapeutic outcomes of RF or other treatment plan for
tendinopathy.
PMID- 24348698
TI - Tropical protozoan diseases: natural product drug discovery and development.
PMID- 24348699
TI - Subacute and Reproductive Oral Toxicity Assessment of the Hydroethanolic Extract
of Jacaranda decurrens Roots in Adult Male Rats.
AB - Jacaranda decurrens subsp. symmetrifoliolata Farias & Proenca (Bignoniaceae) is a
species traditionally used for the treatment of inflammatory and infectious
diseases. Previous findings from our group reported scientifically that J.
decurrens has anti-inflammatory efficacy. However, more toxicological studies are
needed to support and ensure its safe use. The present study was carried out to
evaluate the toxic effects of a prolonged treatment with hydroethanolic root
extract of J. decurrens (EJD) on hematological, biochemical, and reproductive
parameters in adult male rats. The animals received by oral gavage 0; 250; 500;
or 1000 mg/kg body weight of EJD for 28 days. After the treatment, biochemical,
hematological, histopathological, and reproductive parameters were analyzed. The
EJD treatment did not cause adverse effects on body weight gain, feed and water
consumption, hematological and biochemical profiles, or histopathological
analysis of liver and kidney. Similarly, there were no statistically significant
differences in reproductive parameters, such as sperm production, number of sperm
in the epididymis, and sperm morphology. These results demonstrate the absence of
subacute toxicity as a result of the oral treatment with EJD for 28 days in adult
male rats. However, other studies should be performed to evaluate the total
safety of this plant.
PMID- 24348700
TI - An exploratory survey of deqi sensation from the views and experiences of chinese
patients and acupuncturists.
AB - Deqi sensation is believed to be important in clinical efficacy according to TCM
theory. The measuring method of Deqi sensation has significant implications for
the result of research trials. This study makes an investigation on acupuncture
experienced patients and expert acupuncturists in China and aims to find out the
patient's needling sensations and acupuncturist's sensations which can be
acceptable as descriptors of Deqi sensation, so as to provide foundation for more
systematic and sensitive quantitative evaluation method of Deqi sensation.
Results of this survey indicated that the Deqi sensation noted by both patient
and acupuncturist is equally important to the treatment efficacy. It is found
that there are some differences between the patients' real-life experience and
the acupuncturists' expectations on patients' Deqi sensation. The "dull pain,"
"aching," "sore," "numb," "distended," "heavy," "electric," "throbbing,"
"warmness," "coolness," "spreading," and "radiating" can be considered as the
main manifestations of Deqi sensations. The acupuncturists believed that Deqi
sensations were mainly "pulling," "tight," and "throbbing." We suggest developing
a questionnaire measuring the Deqi sensations which includes both the sensations
of the patient and acupuncturist, and this would be very important and necessary
for a better understanding of the relationship between Deqi sensation and
acupuncture effects in future studies.
PMID- 24348701
TI - Treatment of fibromyalgia syndrome: recommendations of recent evidence-based
interdisciplinary guidelines with special emphasis on complementary and
alternative therapies.
AB - Objective. Current evidence indicates that there is no single ideal treatment for
fibromyalgia syndrome (FMS). First choice treatment options remain debatable,
especially concerning the importance of complementary and alternative medicine
(CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on
FMS in Canada, Germany, and Israel were compared for their first choice and CAM
recommendations. Results. All three guidelines emphasized a patient-tailored
approach according to the key symptoms. Aerobic exercise, cognitive behavioral
therapy, and multicomponent therapy were first choice treatments. The guidelines
differed in the grade of recommendation for drug treatment. Anticonvulsants
(gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors
(duloxetine, milnacipran) were strongly recommended by the Canadian and the
Israeli guidelines. These drugs received only a weak recommendation by the German
guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided
imagery, and Tai Chi were recommended by the German and Israeli guidelines. The
Canadian guidelines did not recommend any CAM therapy. Discussion. Recent
evidence-based interdisciplinary guidelines concur on the importance of treatment
tailored to the individual patient and further emphasize the need of self
management strategies (exercise, and psychological techniques).
PMID- 24348702
TI - The sasang constitution as an independent risk factor for metabolic syndrome:
propensity matching analysis.
AB - THE SASANG CONSTITUTIONAL MEDICINE IS A TRADITIONAL KOREAN CUSTOMIZED MEDICINE
THAT CLASSIFIES PEOPLE INTO FOUR TYPES: Tae-eumin (TE), Soyangin (SY), Soeumin
(SE), and Taeyangin. The aim of this study was to show whether the Sasang
Constitution (SC) could be an independent risk factor for the metabolic syndrome
(MS). Totally, 3,334 subjects from 24 Korean medicine clinics participated in
this study. A one-way ANOVA for the continuous variables and a chi-square test
for the prevalence of MS were conducted. A logistic regression was conducted to
calculate the propensity score and the odds ratios (ORs). The prevalence for MS
in TE, SY, and SE was 50.6%, 30.9%, and 17.7% (P < 0.001) before matching, and
36.7%, 28.6% and 28.2% (P = 0.042) after matching, respectively. The TE was
associated with an increased OR for MS compared with the SE and SY in both crude
(OR 4.773, 95% CI 3.889-5.859, and OR 2.292, 95% CI 1.942-2.704, resp.) and
matched groups (OR 1.476, 95% CI 1.043-2.089, and OR 1.452, 95% CI 1.026-2.053,
resp.). This study reveals that the SC, especially the TE type, could be
considered as a risk element for MS even in people with otherwise similar
physical characteristics.
PMID- 24348703
TI - In Vitro Antiproliferative Effect of Arthrocnemum indicum Extracts on Caco-2
Cancer Cells through Cell Cycle Control and Related Phenol LC-TOF-MS
Identification.
AB - This study aimed to determinate phenolic contents and antioxidant activities of
the halophyte Arthrocnemum indicum shoot extracts. Moreover, the anticancer
effect of this plant on human colon cancer cells and the likely underlying
mechanisms were also investigated, and the major phenols were identified by LC
ESI-TOF-MS. Results showed that shoot extracts had an antiproliferative effect of
about 55% as compared to the control and were characterised by substantial total
polyphenol content (19 mg GAE/g DW) and high antioxidant activity (IC50 = 40 MU
g/mL for DPPH test). DAPI staining revealed that these extracts decrease DNA
synthesis and reduce the proliferation of Caco-2 cells which were stopped at the
G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38,
Erk1/2, Chk1, and Chk2) correlate with the changes in cell cycle distribution.
Eight phenolic compounds were also identified. In conclusion, A. indicum showed
interesting antioxidant capacities associated with a significant
antiproliferative effect explained by a cell cycle blocking at the G2/M phase.
Taken together, these data suggest that A. indicum could be a promising candidate
species as a source of anticancer molecules.
PMID- 24348704
TI - The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by
Dermatophagoides farinae Allergen in NC/Nga Mice.
AB - Hydrogen water (HW) produced by electrolysis of water has characteristics of
extremely low oxidation-reduction potential (ORP) value and high dissolved
hydrogen (DH). It has been proved to have various beneficial effects including
antioxidant and anti-inflammatory effects; however, HW effect on atopic
dermatitis (AD), an inflammatory skin disorder, is poorly documented. In the
present study, we examined the immunological effect of drinking HW on
Dermatophagoides farinae-induced AD-like skin in NC/Nga mice. Mice were
administered with HW and purified water (PW) for 25 days. We evaluated the serum
concentration of pro-inflammatory (TNF- alpha ), Th1 (IFN- gamma , IL-2, and IL
12p70), Th2 (IL-4, IL-5, and IL-10), and cytokine expressed by both subsets (GM
CSF) to assess their possible relationship to the severity of AD. The serum
levels of cytokines such as IL-10, TNF- alpha , IL-12p70, and GM-CSF of mice
administered with HW was significantly reduced as compared to PW group. The
results suggest that HW affects allergic contact dermatitis through modulation of
Th1 and Th2 responses in NC/Nga mice. This is the first note on the drinking
effect of HW on AD, clinically implying a promising potential remedy for
treatment of AD.
PMID- 24348705
TI - The long-term effects of a kampo medicine, juzentaihoto, on maintenance of
antibody titer in elderly people after influenza vaccination.
AB - We have performed a broad-ranging analysis of the adjuvant effect of a Kampo
medicine, juzentaihoto (JTT), on influenza vaccination in a multicenter
randomized controlled trial. In this study, the enhancing effect of JTT on
antibody titer after influenza vaccination was studied for 28 weeks in elderly
people who were in the high-risk group for influenza infection. In total, 91
subjects over 65 years old were recruited from four long-term-care facilities
located in Chiba, Gunma, and Toyama prefectures in Japan. Participants were
randomly assigned to the JTT and the control groups. Blood samples were taken at
4 weeks before vaccination, at the time of vaccination, and then at 4, 8, 12, and
24 weeks after vaccination. The hemagglutination inhibition (HI) titers against
A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008
were then manually measured. A significant increase in HI titer against H3N2 was
observed at week 8 after vaccination in the JTT group compared with the control
group (P = 0.0229), and the HI titer of the JTT group significantly increased
from 4 to 24 weeks (P = 0.0468), compared with the control group. In conclusion,
our results indicated that JTT increased and prolonged antibody production
against A/Victoria/210/2009 (H3N2), in particular, after influenza vaccination.
PMID- 24348706
TI - Electroacupuncture regulates apoptosis/proliferation of intramuscular
interstitial cells of cajal and restores colonic motility in diabetic
constipation rats.
AB - Injury of interstitial cells of Cajal (ICC) is associated with gut dysmotility in
diabetic rats. We have shown an acceleration of the colonic contractility by
electroacupuncture stimulation (EAS). However, little is known about potential
roles of EAS on colonic transit and ICC. In this study, we evaluate the effect of
EAS on colonic transit and investigate whether apoptosis/proliferation of ICC was
involved in regulative effect of EAS on colonic transit. Rats were randomly
assigned to normal, diabetic, diabetic-plus-sham stimulation, diabetic-plus-low
frequency stimulation, and diabetic-plus-high-frequency stimulation groups. Bead
expulsion test was used for measuring the distal colonic transit. The Kit (ICC
marker) was detected by western blot. Apoptotic ICC was detected by terminal dUTP
nucleotide end labeling. Proliferating ICC was identified by Kit/Ki67 double
immunofluorescent staining on whole mount preparations. Ultrastructure changes of
ICC were studied using electron microscopy. Results showed that high-frequency
stimulation significantly promoted colonic transit. Low- and high-frequency
stimulation markedly rescued intramuscular ICC from apoptosis. Abundant
proliferating intramuscular ICC was found in low- and high-frequency stimulation
groups. Our results indicate that high-frequency EAS has stimulatory effect on
the distal colonic transit, which may be mediated by downregulation of the
apoptosis and upregulation of the proliferation of intramuscular ICC.
PMID- 24348707
TI - Evaluation of anxiolytic-like effect of aqueous extract of asparagus stem in
mice.
AB - There are few studies on the neuropharmacological properties of asparagus, which
was applied in Chinese traditional medicine as a tonic and heat-clearing agent.
The present study was designed to investigate the anxiolytic-like activity of the
aqueous extract of asparagus stem (AEAS) using elevated plus maze (EPM) and Vogel
conflict tests (VCT) in mice. AEAS significantly increased the percentage of time
spent in open arms in EPM, when compared with control group. In the Vogel
conflict drinking test, the numbers of punished licks increased to 177% and 174%
by the treatment of AEAS at the doses of 1.5 and 3.0 g/kg (250 and 500 mg
sarsasapogenin per kilogram of body weight), compared with control group. The
serum cortisol level decreased significantly, at the same time. In conclusion,
these findings indicated that the aqueous extract of asparagus stem exhibited a
strong anxiolytic-like effect at dose of 1.5 and 3.0 g/kg (250 and 500 mg
sarsasapogenin per kilogram of body weight) in experimental models of anxiety and
may be considered an alternative approach for the management of anxiety disorder.
PMID- 24348708
TI - A network-based systematic study for the mechanism of the treatment of zhengs
related to cough variant asthma.
AB - Traditional Chinese medicine (TCM) has shown significant efficacy in the
treatment of cough variant asthma (CVA), a special type of asthma. However, there
is shortage of explanations for relevant mechanism of treatment. As Zhengs
differentiation is a critical concept in TCM, it is necessary to explain the
mechanism of treatment of Zhengs. Based on TCM clinical cases, this study
illustrated the mechanism of the treatment of three remarkably relevant Zhengs
for CVA: "FengXieFanFei," "FeiQiShiXuan", and "QiDaoLuanJi." To achieve this
goal, five steps were carried out: (1) determining feature Zhengs and
corresponding key herbs of CVA by analyses of clinical cases; (2) finding out
potential targets of the key herbs and clustering them based on their functional
annotations; (3) constructing an ingredient-herb network and an ingredient
network; (4) identifying modules of the ingredient network; (5) illustrating the
mechanism of the treatment by further mining the latent biological implications
within each module. The systematic study reveals that the treatment of
"FengXieFanFei," "FeiQiShiXuan," and "QiDaoLuanJi" has effects on the regulation
of multiple bioprocesses by herbs containing different ingredients with functions
of steroid metabolism regulation, airway inflammation, and ion conduction and
transportation. This network-based systematic study will be a good way to boost
the scientific understanding of mechanism of the treatment of Zhengs.
PMID- 24348709
TI - Rosmarinic Acid and Its Methyl Ester as Antimicrobial Components of the
Hydromethanolic Extract of Hyptis atrorubens Poit. (Lamiaceae).
AB - Primary biological examination of four extracts of the leaves and stems of Hyptis
atrorubens Poit. (Lamiaceae), a plant species used as an antimicrobial agent in
Guadeloupe, allowed us to select the hydromethanolic extract of the stems for
further studies. It was tested against 46 microorganisms in vitro. It was active
against 29 microorganisms. The best antibacterial activity was found against
bacteria, mostly Gram-positive ones. Bioautography enabled the isolation and
identification of four antibacterial compounds from this plant: rosmarinic acid,
methyl rosmarinate, isoquercetin, and hyperoside. The MIC and MBC values of these
compounds and their combinations were determined against eight pathogenic
bacteria. The best inhibitory and bactericidal activity was found for methyl
rosmarinate (0.3 mg/mL). Nevertheless, the bactericidal power of rosmarinic acid
was much faster in the time kill study. Synergistic effects were found when
combining the active compounds. Finally, the inhibitory effects of the compounds
were evaluated on the bacterial growth phases at two different temperatures. Our
study demonstrated for the first time antimicrobial activity of Hyptis atrorubens
with identification of the active compounds. It supports its traditional use in
French West Indies. Although its active compounds need to be further evaluated in
vivo, this work emphasizes plants as potent sources of new antimicrobial agents
when resistance to antibiotics increases dramatically.
PMID- 24348710
TI - Mushrooms and truffles: historical biofactories for complementary medicine in
Africa and in the middle East.
AB - The ethnopharmaceutical approach is important for the discovery and development
of natural product research and requires a deep understanding not only of
biometabolites discovery and profiling but also of cultural and social science.
For millennia, epigeous macrofungi (mushrooms) and hypogeous macrofungi
(truffles) were considered as precious food in many cultures based on their high
nutritional value and characterized pleasant aroma. In African and Middle Eastern
cultures, macrofungi have long history as high nutritional food and were widely
applied in folk medicine. The purpose of this review is to summarize the
available information related to the nutritional and medicinal value of African
and Middle Eastern macrofungi and to highlight their application in complementary
folk medicine in this part of the world.
PMID- 24348711
TI - Yoga and rehabilitation: physical, psychological, and social.
PMID- 24348713
TI - Icariin Augments Bone Formation and Reverses the Phenotypes of Osteoprotegerin
Deficient Mice through the Activation of Wnt/ beta -Catenin-BMP Signaling.
AB - Icariin has been mostly reported to enhance bone fracture healing and treat
postmenopausal osteoporosis in ovariectomized animal model. As another novel
animal model of osteoporosis, there is few publication about the effect of
Icariin on osteoprotegerin-deficient mice. Therefore, the goal of this study is
to find the effect on bone formation and underlying mechanisms of Icariin in
osteoprotegerin (OPG) knockout (KO) mice. We found that Icariin significantly
stimulated new bone formation after local injection over the surface of calvaria
at the dose of 5 mg/kg per day. With this dose, Icariin was also capable of
significantly reversing OPG-deficient-induced bone loss and bone strength
reduction. Real-time PCR analysis showed that Icariin significantly upregulated
the expression of BMP2, BMP4, RUNX2, OC, Wnt1, and Wnt3a in OPG KO mice. Icariin
also significantly increased the expression of AXIN2, DKK1, TCF1, and LEF1, which
are the direct target genes of beta -catenin signaling. The in vitro studies
showed that Icariin induced osteoblast differentiation through the activation of
Wnt/ beta -catenin-BMP signaling by in vitro deletion of the beta -catenin gene
using beta -catenin(fx/fx) mice. Together, our findings demonstrate that Icariin
significantly reverses the phenotypes of OPG-deficient mice through the
activation of Wnt/ beta -catenin-BMP signaling.
PMID- 24348715
TI - Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst
Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.
AB - Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom.
Scientific reports had shown that the wound healing effects of G. lucidum were
partly attributed to its rich polysaccharides. However, little attention has been
paid to its potential effects on wounds associated with diabetes mellitus. In
this study, we evaluated the wound healing activity of the hot aqueous extract of
G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was
standardised based on chemical contents (w/w) of total polysaccharides (25.1%),
ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were
experimentally wounded in the posterior neck region. Intrasite gel was used as a
positive control and aqueous cream as the placebo. Topical application with 10%
(w/w) of mushroom extract-incorporated aqueous cream was more effective than that
with Intrasite gel in terms of wound closure. The antioxidant activity in serum
of rats treated with aqueous extract of G. lucidum was significantly higher;
whereas the oxidative protein products and lipid damage were lower when compared
to those of the controls. These findings strongly support the beneficial effects
of standardised aqueous extract of G. lucidum in accelerating wound healing in
streptozotocin-induced diabetic rats.
PMID- 24348714
TI - Recent Advances in Astragalus membranaceus Anti-Diabetic Research:
Pharmacological Effects of Its Phytochemical Constituents.
AB - The disease burden of diabetes mellitus is increasing throughout the world. The
need for more potent drugs to complement the present anti-diabetic drugs has
become an imperative. Astragalus membranaceus, a key component of most Chinese
herbal anti-diabetic formulas, has been an important prospect for lead anti
diabetic compounds. It has been progressively studied for its anti-diabetic
properties. Ethnopharmacological studies have established its potential to
alleviate diabetes mellitus. Recent studies have sought to relate its chemical
constituents to types 1 and 2 diabetes mellitus. Its total polysaccharides,
saponins, and flavonoids fractions and several isolated compounds have been the
most studied. The total polysaccharides fraction demonstrated activity to both
types 1 and 2 diabetes mellitus. This paper discusses the anti-diabetic effects
and pharmacological action of the chemical constituents in relation to types 1
and 2 diabetes mellitus.
PMID- 24348712
TI - Curcumin and diabetes: a systematic review.
AB - Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger
family, has been used for the treatment of diabetes in Ayurvedic and traditional
Chinese medicine. The active component of turmeric, curcumin, has caught
attention as a potential treatment for diabetes and its complications primarily
because it is a relatively safe and inexpensive drug that reduces glycemia and
hyperlipidemia in rodent models of diabetes. Here, we review the recent
literature on the applications of curcumin for glycemia and diabetes-related
liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular
diseases, pancreatic disorders, and other complications, and we also discuss its
antioxidant and anti-inflammatory properties. The applications of additional
curcuminoid compounds for diabetes prevention and treatment are also included in
this paper. Finally, we mention the approaches that are currently being sought to
generate a "super curcumin" through improvement of the bioavailability to bring
this promising natural product to the forefront of diabetes therapeutics.
PMID- 24348716
TI - Activity-Guided Isolation of Bioactive Constituents with Antinociceptive Activity
from Muntingia calabura L. Leaves Using the Formalin Test.
AB - The present study was conducted to determine the antinociceptive potential of
methanol extract of Muntingia calabura L. (MEMC) and to isolate and identify the
bioactive compound(s) responsible for the observed antinociceptive activity. The
MEMC and its partitions (petroleum ether (PEP), ethyl acetate (EAP), and aqueous
(AQP) partitions), in the dose range of 100, 500, and 1000 mg/kg, were tested
using the formalin-induced nociceptive test. The PEP, which exerted the most
effective activity in the respective early and late phase, was further subjected
to the fractionation procedures and yielded seven fractions (labelled A to G).
These fractions were tested, at the dose of 300 mg/kg, together with distilled
water or 10% DMSO (negative controls); morphine and aspirin (positive controls)
for potential antinociceptive activity. Of all fractions, Fraction D showed the
most significant antinociceptive activity, which is considered as equieffective
to morphine or aspirin in the early or late phase, respectively. Further
isolation and identification processes on fraction D led to the identification of
three known and one new compounds, namely, 5-hydroxy-3,7,8-trimethoxyflavone (1),
3,7-dimethoxy-5-hydroyflavone (2), 2',4'-dihydroxy-3'-methoxychalcone (3), and
calaburone (4). At the dose of 50 mg/kg, compound 3 exhibited the highest
percentage of antinociceptive activity in both phases of the formalin test. In
conclusion, the antinociceptive activity of MEMC involved, partly, the
synergistic activation of the flavonoid types of compounds.
PMID- 24348717
TI - Beneficial Effect of 7-O-Galloyl-D-sedoheptulose, a Polyphenol Isolated from
Corni Fructus, against Diabetes-Induced Alterations in Kidney and Adipose Tissue
of Type 2 Diabetic db/db Mice.
AB - Traditional medicines are being focused on as possible treatments for diabetes
and its complications because of their negligible toxic and/or side effects. In
line with this, our group has reported that Corni Fructus, a traditional medicine
considered exhibiting beneficial effects on liver and kidney functions, possessed
an antidiabetic effect via ameliorating glucose-mediated metabolic disorders. To
add to these findings, we screened the iridoid glycoside fraction containing
morroniside and loganin, and low molecular weight polyphenol fraction containing
7-O-galloyl-d-sedoheptulose (GS) from Corni Fructus. To our knowledge, GS is a
compound only detected in Corni Fructus, and its biological activity has been
poorly understood until now. For these reasons, we examined whether GS has an
ameliorative effect on diabetic changes using type 2 diabetic db/db mice. Our
findings suggest that GS has a beneficial effect on the pathological state of the
serum, kidney, and adipose tissue related to diabetic damage.
PMID- 24348718
TI - Immunosuppression of the trimellitic anhydride-induced th2 response by novel
nonanatural products mixture in mice.
AB - Many natural dietary products prevent or cure allergic inflammation; however, the
ability of mixtures of these natural medicinals to suppress allergic skin
inflammation is unknown. We examined the inhibitory effects of nonanatural
products mixture (NPM-9), which provides immunoregulatory activation, on Th2
mediated skin allergic inflammation. Oral administration of NPM-9 in mice reduced
ear thickness and specific IgE production in trimellitic anhydride- (TMA-)induced
contact hypersensitivity (CHS). NPM-9 also suppressed IL-4 and IL-1beta
production in splenocytes but prevented only TMA-induced IL-1beta production in
inflamed ears. To characterize the mechanism of this effect, we examined NPM-9
immunosuppression on an OVA-induced Th2 allergic state. Oral administration of
NPM-9 inhibited Th2-mediated serum IgE overproduction. NPM-9 also downregulated
the polarized Th2 response, whereas it upregulated Th1 response in splenocytes.
These data suggest that NPM-9 may be a useful therapeutic agent for allergic
inflammatory diseases through its suppression of the Th2-mediated allergic
response.
PMID- 24348720
TI - Evaluation of the effects of honey on acute-phase deep burn wounds.
AB - This study aimed to clarify the effects of honey on acute-phase deep burn wounds.
Two deep burn wounds were created on mice which were divided into four groups: no
treatment, silver sulfadiazine, manuka honey, and Japanese acacia honey. Wound
sizes were calculated as expanded wound areas and sampled 30 minutes and 1-4 days
after wounding for histological observation. The wound sections were subjected to
hematoxylin and eosin and immunohistological staining to detect necrotic cells,
apoptotic cells, neutrophils, and macrophages. The no treatment group formed a
scar. The redness around the wound edges in the silver sulfadiazine group was the
most intense. All groups exhibited increased wound areas after wounding. The
proportions of necrotic cells and the numbers of neutrophils in the manuka and
acacia honey groups were lower than those in the no treatment and silver
sulfadiazine groups until day 3; however, there were no significant differences
between all groups on day 4. These results show that honey treatment on deep burn
wounds cannot prevent wound progression. Moreover, comparing our observations
with those of Jackson, there are some differences between humans and animals in
this regard, and the zone of hyperemia and its surrounding area fall into
necrosis, which contributes to burn wound progression.
PMID- 24348719
TI - Citrus bergamia Risso Elevates Intracellular Ca (2+) in Human Vascular
Endothelial Cells due to Release of Ca (2+) from Primary Intracellular Stores.
AB - The purpose of the present study is to examine the effects of essential oil of
Citrus bergamia Risso (bergamot, BEO) on intracellular Ca(2+) in human umbilical
vein endothelial cells. Fura-2 fluorescence was used to examine changes in
intracellular Ca(2+) concentration [Ca(2+)]i . In the presence of extracellular
Ca(2+), BEO increased [Ca(2+)]i , which was partially inhibited by a nonselective
Ca(2+) channel blocker La(3+). In Ca(2+)-free extracellular solutions, BEO
increased [Ca(2+)]i in a concentration-dependent manner, suggesting that BEO
mobilizes intracellular Ca(2+). BEO-induced [Ca(2+)]i increase was partially
inhibited by a Ca(2+)-induced Ca(2+) release inhibitor dantrolene, a
phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated
Ca(2+) channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased
[Ca(2+)]i in the presence of carbonyl cyanide m-chlorophenylhydrazone, an
inhibitor of mitochondrial Ca(2+) uptake. In addition, store-operated Ca(2+)
entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes
Ca(2+) from primary intracellular stores via Ca(2+)-induced and IP3-mediated
Ca(2+) release and affect promotion of Ca(2+) influx, likely via an SOC
mechanism.
PMID- 24348721
TI - Shenqi fuzheng injection alleviates the transient worsening caused by steroids
pulse therapy in treating myasthenia gravis.
AB - Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng
Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG)
symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six
consecutive patients with MG were randomly divided into two groups: the treatment
group treated with SFI and methylprednisolone pulse therapy (MPT) and the control
group treated with MPT alone. The severity of MG before, during, and after MPT
and the duration of transient worsening (TW) were evaluated and compared with the
clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty
nine patients experienced TW in each group. At TW, the AS was significantly
increased (P < 0.000) in both groups compared with baseline data, with the AS
increase in the treatment group (16.8 +/- 2) significantly smaller (P < 0.05)
than in the control group (24.9 +/- 2.5). At the end of the treatment course, the
AS for the treatment group was significantly decreased (7.5 +/- 0.9) compared
with at TW, although no significant difference compared with the control (9.7 +/-
1.1). The TW lasted 1-6 days (mean 3.7) for the treatment group, significantly
shorter (P < 0.05) than 2-12 days (mean 7.8) for the control. The RS for the
treatment group at the end of treatment was 43.8%-100% (mean 76.8% +/- 2.6%),
significantly better than the control group: 33.3%-100% (mean 67.2 +/- 3.6%).
Slight side effects (18.75%) included maldigestion and rash in the treatment
group. Conclusion. SFI has a better treatment effect and few side effects and can
alleviate the severity and shorten the duration of the transient worsening of MG
during steroids pulse therapy.
PMID- 24348722
TI - Compassionate Love as a Predictor of Reduced HIV Disease Progression and
Transmission Risk.
AB - Objectives. This study examined if compassionate love (CL) predicts HIV disease
progression and transmission risk. Scientific study of CL emerged with
Underwood's working model of other-centered CL, defining five criteria: free
choice, cognitive understanding, valuing/empowering, openness/receptivity for
spirituality, and response of the heart. Method. This 10-year cohort study
collected 6-monthly interviews/essays on coping with HIV and trauma of 177 people
with HIV in South Florida. Secondary qualitative content analysis on other
centered CL inductively added the component of CL towards self. Deductively, we
coded the presence of the five criteria of CL and rated the benefit of CL for the
recipient on a 6-point Likert scale. Growth-curve modeling (reduced to 4 years
due to cohort effects) investigated if CL predicts CD4 slope (HIV disease
progression) and cumulative viral load detection (transmission risk). Results.
Valuing/empowering and cognitive understanding were the essential criteria for CL
to confer long-term benefits. CL had a higher benefit for recipients if given out
of free choice. High scores of CL towards self were reciprocal with receiving
(93%) and giving (77%) other-centered CL. Conversely, those rated low on CL
towards self were least likely to score high on receiving (38%) and giving (49%)
other-centered CL. Growth-curve modeling showed that CL towards self predicted 4
year cumulative undetectable viral load (independent from sociocultural
differences, substance use disorder, baseline CD4 and viral load). Those high
versus low on CL self were 2.25 times more likely to have undetectable viral load
at baseline and 1.49 times more likely to maintain undetectable viral load over
time. CL towards self predicted CD4 preservation after controlling for
differences in CL giving. Conclusions. CL towards self is potentially the seed of
being expressive and receptive of CL. Health care professionals prepared to walk
the extra mile for those who neglect and isolate themselves may break a vicious
circle since those lacking CL self were least likely to receive CL from others.
Future studies should examine whether any enhancement of CL towards self may
translate into slower disease progression and reduction of transmission risk.
PMID- 24348723
TI - A brief analysis of traditional chinese medical elongated needle therapy on acute
spinal cord injury and its mechanism.
AB - Acute spinal cord injury is one of the most common and complicated diseases among
human spinal injury. We aimed to explore the effect of point-through-point
acupuncture therapy with elongated needles on acute spinal cord injury in rabbits
and its possible mechanism. Adult rabbits were randomly divided into a model
group, elongated needle therapy group, and blank group. Immunohistochemical
staining showed that the protein levels of Fas and caspase-3 in the model group
were significantly higher than those in the blank group at each time point (P <
0.05) and significantly lower than those in the elongated needle therapy group on
the 3rd and 5th days after operation (P < 0.05). RT-PCR showed that Fas and
caspase-3 mRNA levels in the model group and elongated needle therapy group were
significantly higher than those in the blank group (P < 0.05, 0.01). The mRNA
levels of Fas and caspase-3 in the elongated needle therapy group were
significantly lower than those in model group on the 3rd day (P < 0.05, 0.01).
Therefore, we confirmed that elongated needle therapy has an obvious effect on
acute spinal cord injury in rabbits. Its mechanism is made possible by inhibiting
the expression of the Fas->caspase-3 cascade, thereby inhibiting cell apoptosis
after spinal cord injury.
PMID- 24348724
TI - Clinical effect of acupuncture on endemic skeletal fluorosis: a randomized
controlled trial.
AB - Objective. To evaluate the effect of acupuncture on endemic skeletal fluorosis
(ESF) through the randomized controlled trial. Methods. Ninety-nine cases were
divided into the treatment group (68 cases) and the control group (31 cases)
randomly. Normal acupuncture combined with electroacupuncture was used in
treatment group, while Caltrate with vitamin D tablets were applied in control
group. After 2 courses, the VAS, urinary fluoride, serum calcium, and serum
phosphate were evaluated before and after treatment. Results. Both of these two
methods could relieve pain effectively and the effect of acupuncture was better
(P < 0.05). In treatment group, the content of urinary fluoride after treatment
was higher than before (P < 0.05), while the content of serum calcium and
phosphate was lower (P < 0.05). Conclusion. The effect of acupuncture on
relieving pain and promoting discharge of urinary fluoride is better than that of
western medicine. Acupuncture can reduce the content of serum calcium and
phosphate.
PMID- 24348725
TI - What the iberian conquest bequeathed to us: the fruit trees introduced in
argentine subtropic-their history and importance in present traditional medicine.
AB - This contribution presents information about the history of introduction,
establishment, and local appropriation of Eurasian fruit trees-species and
varieties of the genera Prunus and Citrus-from 15th century in two rural areas of
Northern Argentina. By means of an ethnobotanical and ethnohistorical approach,
our study was aimed at analysing how this process influenced local medicine and
the design of cultural landscape that they are still part of. As a first step,
local diversity, knowledge, and management practices of these fruit tree species
were surveyed. In a second moment, medicinal properties attributed to them were
documented. A historical literature was consulted referring to different aspects
on introduction of peaches and citric species into America and their uses in the
past. The appropriation of these fruit-trees gave place to new applications and a
particular status for introduced species that are seen as identitary and
contribute to the definition of the communities and daily life landscapes.
Besides, these plants, introduced in a relatively short period and with written
record, allow the researcher to understand and to design landscape domestication,
as a multidimensional result of physical, social, and symbolic environment.
PMID- 24348726
TI - Greenselect phytosome for borderline metabolic syndrome.
AB - The beneficial effects of Greenselect Phytosome, a proprietary lecithin
formulation of a caffeine-free green tea catechin extract, were evaluated in a
controlled registry study on 50 asymptomatic subjects borderline for metabolic
syndrome factors and with increased plasma oxidative stress. After 24 weeks of
intervention, improvement in weight, blood lipid profile, and blood pressure
positioned 68% of subjects in the treatment arm out of the metabolic syndrome
profile, while 80% of the subjects in the control group still remained in their
initial borderline disease signature. Compared to the control (lifestyle and
dietary changes alone), Greenselect Phytosome was especially effective for
weight/waist changes. These results highlight the relevance of addressing
multiple factors involved in the development of metabolic syndrome with a
pleiotropic agent capable of improving the beneficial effects of lifestyle and
dietary changes and foster the attainment of a globally improved health profile.
PMID- 24348727
TI - Chinese herbal medicine for postinfectious cough: a systematic review of
randomized controlled trials.
AB - Chinese herbal medicine has been commonly used in the treatment of postinfectious
cough. The aim of this review is to systematically evaluate the efficacy and
safety of Chinese herbal medicine for postinfectious cough. An extensive search
for RCTs was performed using multiple electronic databases, supplemented with a
manual search. All studies included were confirmed with specific inclusion
criteria. Methodological quality of each study was examined according to the
Cochrane risk of bias assessment. Quality of evidence was evaluated using rating
approach developed by GRADE working group. The literature search yielded 352
results, of which 12 RCTs satisfied the inclusion criteria, offering moderate-to
high levels of evidence. Methodological quality was considered high in three
trials, while in the other nine studies the unclear risk of bias was in the
majority. Findings suggested that, compared with western conventional medicine or
placebo, Chinese herbal medicine could effectively improve core symptoms of
postinfectious cough, act better and have earlier antitussive effect, and enhance
patients' quality of life. No serious adverse event was reported.
PMID- 24348728
TI - Flavonoids Identified from Korean Scutellaria baicalensis Georgi Inhibit
Inflammatory Signaling by Suppressing Activation of NF- kappa B and MAPK in RAW
264.7 Cells.
AB - Scutellaria baicalensis Georgi has been used as traditional medicine for treating
inflammatory diseases, hepatitis, tumors, and diarrhea in Asia. Hence, we
investigated the anti-inflammatory effect and determined the molecular mechanism
of action of flavonoids isolated from Korean S. baicalensis G. in
lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. A 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to
examine cytotoxicity of the flavonoids at various concentrations of 10, 40, 70,
and 100 ug/mL. No cytotoxicity was observed in RAW 264.7 cells at these
concentrations. Furthermore, the flavonoids decreased production of inflammatory
mediators such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin
6, and tumor necrosis factor-alpha and inhibited phosphorylation of nuclear
factor-kappa B (NF- kappa B) and mitogen-activated protein kinases (MAPKs) in LPS
induced RAW 264.7 cells. Moreover, to identify the differentially expressed
proteins in RAW 264.7 cells of the control, LPS-treated, and flavonoid-treated
groups, two-dimensional gel electrophoresis and mass spectrometry were conducted.
The identified proteins were involved in the inflammatory response and included
PRKA anchor protein and heat shock protein 70 kD. These findings suggest that the
flavonoids isolated from S. baicalensis G. might have anti-inflammatory effects
that regulate the expression of inflammatory mediators by inhibiting the NF-
kappa B signaling pathway via the MAPK signaling pathway in RAW 264.7 cells.
PMID- 24348729
TI - Effectiveness of Interstitial Laser Acupuncture Depends upon Dosage: Experimental
Results from Electrocardiographic and Electrocorticographic Recordings.
AB - The purpose of this study was to evaluate the influence of the duration of
interstitial laser acupuncture therapy effects on neurovegetative and
neurobioelectrical parameters like heart rate (HR), heart rate variability (HRV),
and electroencephalogram (EEG). We investigated 6 male Sprague-Dawley rats. They
underwent 10 min, 20 min, and 30 min interstitial laser acupuncture (in
randomized order, with a break of at least 30 min between the different
measurement conditions) at the acupoint Neiguan. HR changed significantly only
during 20 min red laser stimulation, whereas 10 and 30 min stimulation did not
induce significant changes. HRV did not change significantly during any of the
different durations; however, an increase was found during 20 min irradiation.
Neither the LF/HF ratio of HRV nor the integrated EEG showed significant changes.
In this study, it could be experimentally proved that some effects of laser
acupuncture are time dependent, and therefore the dosage, as well known from
theory, also depends on the time factor. We could especially demonstrate that
different treatment times lead to different effects on neurovegetative and
neurobioelectrical parameters. Further studies are needed to verify or refute
these results.
PMID- 24348730
TI - Effects of pretreatment with a combination of melatonin and electroacupuncture in
a rat model of transient focal cerebral ischemia.
AB - Both melatonin and electroacupuncture (EA) have been suggested to be effective
treatments against stroke. However, it is unknown whether a combination of these
two therapies could be beneficial against transient focal cerebral ischemia. The
present study investigated the effects of pretreatment of a combination of
melatonin and EA in a rat model of transient middle cerebral artery occlusion
(MCAO). After pretreatment of melatonin plus EA (MEA), transient MCAO was induced
for 90 minutes in male Sprague-Dawley (SD) rats. The neurological deficit score,
brain infarct volume, cerebral edema ratio, neuronal inflammation, and apoptosis
were evaluated 24 hours after transient MCAO. The expression of related
inflammatory and apoptotic mediators in the brain was also investigated. The
results showed that MEA improved neurological outcome, reduced brain infarct
volume, and inhibited neuronal inflammation as well as apoptosis 24 hours after
transient MCAO. The beneficial effects may derive from downregulation of
proinflammatory and proapoptotic mediators and upregulation of antiapoptotic
mediators. Thus, these results suggest a preventive effect of pretreatment of MEA
on transient focal cerebral ischemia.
PMID- 24348731
TI - Understanding Acupuncture Based on ZHENG Classification from System Perspective.
AB - Acupuncture is an efficient therapy method originated in ancient China, the study
of which based on ZHENG classification is a systematic research on understanding
its complexity. The system perspective is contributed to understand the essence
of phenomena, and, as the coming of the system biology era, broader technology
platforms such as omics technologies were established for the objective study of
traditional chinese medicine (TCM). Omics technologies could dynamically
determine molecular components of various levels, which could achieve a
systematic understanding of acupuncture by finding out the relationships of
various response parts. After reviewing the literature of acupuncture studied by
omics approaches, the following points were found. Firstly, with the help of
omics approaches, acupuncture was found to be able to treat diseases by
regulating the neuroendocrine immune (NEI) network and the change of which could
reflect the global effect of acupuncture. Secondly, the global effect of
acupuncture could reflect ZHENG information at certain structure and function
levels, which might reveal the mechanism of Meridian and Acupoint Specificity.
Furthermore, based on comprehensive ZHENG classification, omics researches could
help us understand the action characteristics of acupoints and the molecular
mechanisms of their synergistic effect.
PMID- 24348732
TI - Tai chi chuan exercise for patients with cardiovascular disease.
AB - Exercise training is the cornerstone of rehabilitation for patients with
cardiovascular disease (CVD). Although high-intensity exercise has significant
cardiovascular benefits, light-to-moderate intensity aerobic exercise also offers
health benefits. With lower-intensity workouts, patients may be able to exercise
for longer periods of time and increase the acceptance of exercise, particularly
in unfit and elderly patients. Tai Chi Chuan (Tai Chi) is a traditional Chinese
mind-body exercise. The exercise intensity of Tai Chi is light to moderate,
depending on its training style, posture, and duration. Previous research has
shown that Tai Chi enhances aerobic capacity, muscular strength, balance, and
psychological well-being. Additionally, Tai Chi training has significant benefits
for common cardiovascular risk factors, such as hypertension, diabetes mellitus,
dyslipidemia, poor exercise capacity, endothelial dysfunction, and depression.
Tai Chi is safe and effective in patients with acute myocardial infarction (AMI),
coronary artery bypass grafting (CABG) surgery, congestive heart failure (HF),
and stroke. In conclusion, Tai Chi has significant benefits to patients with
cardiovascular disease, and it may be prescribed as an alternative exercise
program for selected patients with CVD.
PMID- 24348733
TI - Nonnegative mixed-norm convex optimization for mitotic cell detection in phase
contrast microscopy.
AB - This paper proposes a nonnegative mix-norm convex optimization method for mitotic
cell detection. First, we apply an imaging model-based microscopy image
segmentation method that exploits phase contrast optics to extract mitotic
candidates in the input images. Then, a convex objective function regularized by
mix-norm with nonnegative constraint is proposed to induce sparsity and
consistence for discriminative representation of deformable objects in a sparse
representation scheme. At last, a Support Vector Machine classifier is utilized
for mitotic cell modeling and detection. This method can overcome the difficulty
in feature formulation for deformable objects and is independent of tracking or
temporal inference model. The comparison experiments demonstrate that the
proposed method can produce competing results with the state-of-the-art methods.
PMID- 24348734
TI - Regularized multidirections and multiscales anisotropic diffusion for sinogram
restoration of low-dosed computed tomography.
AB - Although most of existing anisotropic diffusion (AD) methods are supported by
prefect mathematical theories, they still lead to smoothed edges and anatomy
details (EADs). They are caused by not considering the discrete nature of digital
signal. In order to improve the performance of AD in sinogram restoration of low
dosed computed tomography (LDCT), we propose a new AD method, named regularized
multidirections and multiscales anisotropic diffusion (RMDMS-AD), by extending AD
to regularized AD (RAD) in multidirections and multiscales. Since the
multidirections can reduce the discrete errors to the maximum extent, meanwhile
multiscales and RAD make searching neighborhood of solution be as large as
possible which can get more optimal solution to AD, the new proposed method can
improve the performance of AD both in denoising and in stability of solution.
Moreover, the discrete errors and ill-posed solutions occur mostly near the EADs;
the RMDMS-AD will also preserve EADs well. Comparing the proposed new method to
existing AD methods using real sinogram, the new method shows good performance in
EADs preserving while denoising and suppressing artifacts.
PMID- 24348735
TI - Lp-norm regularization in volumetric imaging of cardiac current sources.
AB - Advances in computer vision have substantially improved our ability to analyze
the structure and mechanics of the heart. In comparison, our ability to observe
and analyze cardiac electrical activities is much limited. The progress to
computationally reconstruct cardiac current sources from noninvasive voltage data
sensed on the body surface has been hindered by the ill-posedness and the lack of
a unique solution of the reconstruction problem. Common L2- and L1-norm
regularizations tend to produce a solution that is either too diffused or too
scattered to reflect the complex spatial structure of current source distribution
in the heart. In this work, we propose a general regularization with Lp-norm (1 <
p < 2) constraint to bridge the gap and balance between an overly smeared and
overly focal solution in cardiac source reconstruction. In a set of phantom
experiments, we demonstrate the superiority of the proposed Lp-norm method over
its L1 and L2 counterparts in imaging cardiac current sources with increasing
extents. Through computer-simulated and real-data experiments, we further
demonstrate the feasibility of the proposed method in imaging the complex
structure of excitation wavefront, as well as current sources distributed along
the postinfarction scar border. This ability to preserve the spatial structure of
source distribution is important for revealing the potential disruption to the
normal heart excitation.
PMID- 24348737
TI - A novel CT imaging system with adjacent double X-ray sources.
AB - Current computed tomography (CT) scanners rotate fast to reduce motion artifact.
X-ray tube must work in a high power to make the image clear under short exposure
time. However, the life span of such a tube may be shortened. In this paper, we
propose a novel double sources CT imaging system, which puts two of the same X
ray sources closely with each other. The system is different from current dual
source CT with orthogonal X-ray sources. In our system, each projection is taken
twice by these two sources to enhance the exposure value and then recovered to a
single source projection for image reconstruction. The proposed system can work
like normal single source CT system, while halving down the working power for
each tube.
PMID- 24348736
TI - Fast and automatic ultrasound simulation from CT images.
AB - Ultrasound is currently widely used in clinical diagnosis because of its fast and
safe imaging principles. As the anatomical structures present in an ultrasound
image are not as clear as CT or MRI. Physicians usually need advance clinical
knowledge and experience to distinguish diseased tissues. Fast simulation of
ultrasound provides a cost-effective way for the training and correlation of
ultrasound and the anatomic structures. In this paper, a novel method is proposed
for fast simulation of ultrasound from a CT image. A multiscale method is
developed to enhance tubular structures so as to simulate the blood flow. The
acoustic response of common tissues is generated by weighted integration of
adjacent regions on the ultrasound propagation path in the CT image, from which
parameters, including attenuation, reflection, scattering, and noise, are
estimated simultaneously. The thin-plate spline interpolation method is employed
to transform the simulation image between polar and rectangular coordinate
systems. The Kaiser window function is utilized to produce integration and radial
blurring effects of multiple transducer elements. Experimental results show that
the developed method is very fast and effective, allowing realistic ultrasound to
be fast generated. Given that the developed method is fully automatic, it can be
utilized for ultrasound guided navigation in clinical practice and for training
purpose.
PMID- 24348738
TI - Vascular tree segmentation in medical images using Hessian-based multiscale
filtering and level set method.
AB - Vascular segmentation plays an important role in medical image analysis. A novel
technique for the automatic extraction of vascular trees from 2D medical images
is presented, which combines Hessian-based multiscale filtering and a modified
level set method. In the proposed algorithm, the morphological top-hat
transformation is firstly adopted to attenuate background. Then Hessian-based
multiscale filtering is used to enhance vascular structures by combining Hessian
matrix with Gaussian convolution to tune the filtering response to the specific
scales. Because Gaussian convolution tends to blur vessel boundaries, which makes
scale selection inaccurate, an improved level set method is finally proposed to
extract vascular structures by introducing an external constrained term related
to the standard deviation of Gaussian function into the traditional level set.
Our approach was tested on synthetic images with vascular-like structures and 2D
slices extracted from real 3D abdomen magnetic resonance angiography (MRA) images
along the coronal plane. The segmentation rates for synthetic images are above
95%. The results for MRA images demonstrate that the proposed method can extract
most of the vascular structures successfully and accurately in visualization.
Therefore, the proposed method is effective for the vascular tree extraction in
medical images.
PMID- 24348739
TI - Modeling the chemoelectromechanical behavior of skeletal muscle using the
parallel open-source software library OpenCMISS.
AB - An extensible, flexible, multiscale, and multiphysics model for nonisometric
skeletal muscle behavior is presented. The skeletal muscle chemoelectromechanical
model is based on a bottom-up approach modeling the entire excitation-contraction
pathway by strongly coupling a detailed biophysical model of a half-sarcomere to
the propagation of action potentials along skeletal muscle fibers and linking
cellular parameters to a transversely isotropic continuum-mechanical constitutive
equation describing the overall mechanical behavior of skeletal muscle tissue.
Since the multiscale model exhibits separable time scales, a special emphasis is
placed on employing computationally efficient staggered solution schemes.
Further, the implementation builds on the open-source software library OpenCMISS
and uses state-of-the-art parallelization techniques taking advantage of the
unique anatomical fiber architecture of skeletal muscles. OpenCMISS utilizes
standardized data structures for geometrical aspects (FieldML) and cellular
models (CellML). Both standards are designed to allow for a maximum flexibility,
reproducibility, and extensibility. The results demonstrate the model's
capability of simulating different aspects of nonisometric muscle contraction and
efficiently simulating the chemoelectromechanical behavior in complex skeletal
muscles such as the tibialis anterior muscle.
PMID- 24348740
TI - Local temporal correlation common spatial patterns for single trial EEG
classification during motor imagery.
AB - Common spatial pattern (CSP) is one of the most popular and effective feature
extraction methods for motor imagery-based brain-computer interface (BCI), but
the inherent drawback of CSP is that the estimation of the covariance matrices is
sensitive to noise. In this work, local temporal correlation (LTC) information
was introduced to further improve the covariance matrices estimation (LTCCSP).
Compared to the Euclidean distance used in a previous CSP variant named local
temporal CSP (LTCSP), the correlation may be a more reasonable metric to measure
the similarity of activated spatial patterns existing in motor imagery period.
Numerical comparisons among CSP, LTCSP, and LTCCSP were quantitatively conducted
on the simulated datasets by adding outliers to Dataset IVa of BCI Competition
III and Dataset IIa of BCI Competition IV, respectively. Results showed that
LTCCSP achieves the highest average classification accuracies in all the outliers
occurrence frequencies. The application of the three methods to the EEG dataset
recorded in our laboratory also demonstrated that LTCCSP achieves the highest
average accuracy. The above results consistently indicate that LTCCSP would be a
promising method for practical motor imagery BCI application.
PMID- 24348741
TI - Power and stability properties of resampling-based multiple testing procedures
with applications to gene oncology studies.
AB - Resampling-based multiple testing procedures are widely used in genomic studies
to identify differentially expressed genes and to conduct genome-wide association
studies. However, the power and stability properties of these popular resampling
based multiple testing procedures have not been extensively evaluated. Our study
focuses on investigating the power and stability of seven resampling-based
multiple testing procedures frequently used in high-throughput data analysis for
small sample size data through simulations and gene oncology examples. The
bootstrap single-step minP procedure and the bootstrap step-down minP procedure
perform the best among all tested procedures, when sample size is as small as 3
in each group and either familywise error rate or false discovery rate control is
desired. When sample size increases to 12 and false discovery rate control is
desired, the permutation maxT procedure and the permutation minP procedure
perform best. Our results provide guidance for high-throughput data analysis when
sample size is small.
PMID- 24348742
TI - Low-dose and scatter-free cone-beam CT imaging using a stationary beam blocker in
a single scan: phantom studies.
AB - Excessive imaging dose from repeated scans and poor image quality mainly due to
scatter contamination are the two bottlenecks of cone-beam CT (CBCT) imaging.
Compressed sensing (CS) reconstruction algorithms show promises in recovering
faithful signals from low-dose projection data but do not serve well the needs of
accurate CBCT imaging if effective scatter correction is not in place. Scatter
can be accurately measured and removed using measurement-based methods. However,
these approaches are considered unpractical in the conventional FDK
reconstruction, due to the inevitable primary loss for scatter measurement. We
combine measurement-based scatter correction and CS-based iterative
reconstruction to generate scatter-free images from low-dose projections. We
distribute blocked areas on the detector where primary signals are considered
redundant in a full scan. Scatter distribution is estimated by
interpolating/extrapolating measured scatter samples inside blocked areas. CS
based iterative reconstruction is finally carried out on the undersampled data to
obtain scatter-free and low-dose CBCT images. With only 25% of conventional full
scan dose, our method reduces the average CT number error from 250 HU to 24 HU
and increases the contrast by a factor of 2.1 on Catphan 600 phantom. On an
anthropomorphic head phantom, the average CT number error is reduced from 224 HU
to 10 HU in the central uniform area.
PMID- 24348743
TI - Transformation of physical DVHs to radiobiologically equivalent ones in
hypofractionated radiotherapy analyzing dosimetric and clinical parameters: a
practical approach for routine clinical practice in radiation oncology.
AB - PURPOSE: The purpose of this study was to transform DVHs from physical to
radiobiological ones as well as to evaluate their reliability by correlations of
dosimetric and clinical parameters for 50 patients with prostate cancer and 50
patients with breast cancer, who were submitted to Hypofractionated Radiotherapy.
METHODS AND MATERIALS: To achieve this transformation, we used both the linear
quadratic model (LQ model) and the Niemierko model. The outcome of
radiobiological DVHs was correlated with acute toxicity score according to
EORTC/RTOG criteria. RESULTS: Concerning the prostate radiotherapy, there was a
significant correlation between RTOG acute rectal toxicity and D50 (P < 0.001)
and V60 (P = 0.001) dosimetric parameters, calculated for alpha/beta = 10 Gy.
Moreover, concerning the breast radiotherapy there was a significant correlation
between RTOG skin toxicity and V(>=60) dosimetric parameter, calculated for both
alpha/beta = 2.3 Gy (P < 0.001) and alpha/beta = 10 Gy (P < 0.001). The new tool
seems reliable and user-friendly. CONCLUSIONS: Our proposed model seems user
friendly. Its reliability in terms of agreement with the presented acute
radiation induced toxicity was satisfactory. However, more patients are needed to
extract safe conclusions.
PMID- 24348744
TI - Mathematical modeling of the HIV/Kaposi's sarcoma coinfection dynamics in areas
of high HIV prevalence.
AB - We formulate a deterministic system of ordinary differential equations to
quantify HAART treatment levels for patients co-infected with HIV and Kaposi's
Sarcoma in a high HIV prevalence setting. A qualitative stability analysis of the
equilibrium states is carried out and we find that the disease-free equilibrium
is globally attracting whenever the reproductive number Rk < 1. A unique endemic
equilibrium exists and is locally stable whenever Rk > 1. Therefore, reducing Rk
to below unity should be the goal for disease eradication. Provision of HAART is
shown to provide dual benefit of reducing HIV spread and the risk of acquiring
another fatal disease for HIV/AIDS patients. By providing treatment to 10% of the
HIV population, about 87% of the AIDS population acquire protection against
coinfection with HIV and Kaposi's Sarcoma (KS). Most sub-Sahara African countries
already have programmes in place to screen HIV. Our recommendation is that these
programmes should be expanded to include testing for HHV-8 and KS counseling.
PMID- 24348745
TI - Three-dimensional reconstruction of coronary arteries and its application in
localization of coronary artery segments corresponding to myocardial segments
identified by transthoracic echocardiography.
AB - OBJECTIVES: To establish 3D models of coronary arteries (CA) and study their
application in localization of CA segments identified by Transthoracic
Echocardiography (TTE). METHODS: Sectional images of the heart collected from the
first CVH dataset and contrast CT data were used to establish 3D models of the
CA. Virtual dissection was performed on the 3D models to simulate the
conventional sections of TTE. Then, we used 2D ultrasound, speckle tracking
imaging (STI), and 2D ultrasound plus 3D CA models to diagnose 170 patients and
compare the results to coronary angiography (CAG). RESULTS: 3D models of CA
distinctly displayed both 3D structure and 2D sections of CA. This simulated TTE
imaging in any plane and showed the CA segments that corresponded to 17
myocardial segments identified by TTE. The localization accuracy showed a
significant difference between 2D ultrasound and 2D ultrasound plus 3D CA model
in the severe stenosis group (P < 0.05) and in the mild-to-moderate stenosis
group (P < 0.05). CONCLUSIONS: These innovative modeling techniques help
clinicians identify the CA segments that correspond to myocardial segments
typically shown in TTE sectional images, thereby increasing the accuracy of the
TTE-based diagnosis of CHD.
PMID- 24348747
TI - GPU-based block-wise nonlocal means denoising for 3D ultrasound images.
AB - Speckle suppression plays an important role in improving ultrasound (US) image
quality. While lots of algorithms have been proposed for 2D US image denoising
with remarkable filtering quality, there is relatively less work done on 3D
ultrasound speckle suppression, where the whole volume data rather than just one
frame needs to be considered. Then, the most crucial problem with 3D US denoising
is that the computational complexity increases tremendously. The nonlocal means
(NLM) provides an effective method for speckle suppression in US images. In this
paper, a programmable graphic-processor-unit- (GPU-) based fast NLM filter is
proposed for 3D ultrasound speckle reduction. A Gamma distribution noise model,
which is able to reliably capture image statistics for Log-compressed ultrasound
images, was used for the 3D block-wise NLM filter on basis of Bayesian framework.
The most significant aspect of our method was the adopting of powerful data
parallel computing capability of GPU to improve the overall efficiency.
Experimental results demonstrate that the proposed method can enormously
accelerate the algorithm.
PMID- 24348746
TI - A gradient boosting algorithm for survival analysis via direct optimization of
concordance index.
AB - Survival analysis focuses on modeling and predicting the time to an event of
interest. Many statistical models have been proposed for survival analysis. They
often impose strong assumptions on hazard functions, which describe how the risk
of an event changes over time depending on covariates associated with each
individual. In particular, the prevalent proportional hazards model assumes that
covariates are multiplicatively related to the hazard. Here we propose a
nonparametric model for survival analysis that does not explicitly assume
particular forms of hazard functions. Our nonparametric model utilizes an
ensemble of regression trees to determine how the hazard function varies
according to the associated covariates. The ensemble model is trained using a
gradient boosting method to optimize a smoothed approximation of the concordance
index, which is one of the most widely used metrics in survival model performance
evaluation. We implemented our model in a software package called GBMCI (gradient
boosting machine for concordance index) and benchmarked the performance of our
model against other popular survival models with a large-scale breast cancer
prognosis dataset. Our experiment shows that GBMCI consistently outperforms other
methods based on a number of covariate settings. GBMCI is implemented in R and is
freely available online.
PMID- 24348748
TI - Evaluation of treatment in the Smart Home IRIS in terms of functional
independence and occupational performance and satisfaction.
AB - The development of assistive technologies, home modifications, and smart homes
has rapidly advanced in the last two decades. Health professionals have
recognised the benefits of these technologies in improving individual's quality
of life. The Smart Home IRIS was established in 2008 within the University
Rehabilitation Institute in Ljubljana with the aim to enable persons with
disabilities and elderly people to test various assistive technologies and
technical solutions for their independent living. We investigated the effect of
treatments in the Smart Home IRIS. A convenience sample of 59 persons with
disabilities and elderly people (aged 24-81 years) who were treated in the Smart
Home IRIS from April to December 2011 participated. Standardised instruments--the
Canadian Occupational Performance Measure (COPM) and the Functional Independence
Measure (FIM)--were administered at the first assessment in the Smart Home IRIS
and at a second assessment at the participant's home after 6-12 months. All the
outcomes statistically significantly improved from the first to the second
assessment. The treatments in the Smart Home IRIS appeared to contribute to
higher occupational performance and satisfaction with performance and higher
functional independence of persons with disabilities and elderly people.
PMID- 24348749
TI - A voxel-map quantitative analysis approach for atherosclerotic noncalcified
plaques of the coronary artery tree.
AB - Noncalcified plaques (NCPs) are associated with the presence of lipid-core
plaques that are prone to rupture. Thus, it is important to detect and monitor
the development of NCPs. Contrast-enhanced coronary Computed Tomography
Angiography (CTA) is a potential imaging technique to identify atherosclerotic
plaques in the whole coronary tree, but it fails to provide information about
vessel walls. In order to overcome the limitations of coronary CTA and provide
more meaningful quantitative information for percutaneous coronary intervention
(PCI), we proposed a Voxel-Map based on mathematical morphology to quantitatively
analyze the noncalcified plaques on a three-dimensional coronary artery wall
model (3D-CAWM). This approach is a combination of Voxel-Map analysis techniques,
plaque locating, and anatomical location related labeling, which show more
detailed and comprehensive coronary tree wall visualization.
PMID- 24348750
TI - InterRett, a model for international data collection in a rare genetic disorder.
AB - Rett syndrome (RTT) is a rare genetic disorder within the autistic spectrum. This
study compared socio-demographic, clinical and genetic characteristics of the
international database, InterRett, and the population based Australian Rett
syndrome database (ARSD). It also explored the strengths and limitations of
InterRett in comparison with other studies. A literature review compared
InterRett with RTT population-based and case-based studies of thirty or more
cases that investigated genotype and/or phenotype relationships. Questionnaire
data were used to determine case status and to investigate the comparability of
InterRett and ARSD. Twenty four case series, five population based studies and a
MECP2 mutation database were identified of which twenty one (70%) collected
phenotype and genotype data. Only three studies were representative of their
underlying case population and many had low numbers. Of one thousand one hundred
and fourteen InterRett subjects, nine hundred and thirty five born after 1976
could be verified as Rett cases and compared with the two hundred and ninety five
ARSD subjects. Although more InterRett families had higher education and
occupation levels and their children were marginally less severe, the
distribution of MECP2 mutation types was similar. The InterRett can be used with
confidence to investigate genotype phenotype associations and clinical variation
in RTT and provides an exemplary international model for other rare disorders.
PMID- 24348752
TI - A Pocock approach to sequential meta-analysis of clinical trials.
AB - Three recent papers have provided sequential methods for meta-analysis of two
treatment randomized clinical trials. This paper provides an alternate approach
that has three desirable features. First, when carried out prospectively (i.e.,
we only have the results up to the time of our current analysis), we do not
require knowledge of the information fraction (the fraction of the total
information that is available at each analysis). Second, the methods work even if
the expected values of the effect sizes vary from study to study. Finally, our
methods have easily interpretable metrics that make sense under changing effect
sizes. Although the other published methods can be adapted to be "group
sequential" (recommended), meaning that a set number and timing of looks are
specified, rather than looking after every trial, ours can be used in both a
continuous or group sequential manner. We provide an example on the role of
probiotics in preventing necrotizing enterocolitis in preterm infants.
PMID- 24348751
TI - Advances in Therapeutic Options for Gait and Balance in Parkinson's Disease.
AB - There is a need to explore non-dopaminergic approaches to treating balance and
gait problems in PD. There is emerging evidence on the role of cholinergic
denervation of the PPN-thalamus system and falls in PD. Preliminary clinical
trial data suggest that the subgroup of PD patients with frequent falls may be
suitable candidates for future cholinergic augmentation clinical trials. Recent
controlled clinical trials using methylphenidate have been unable to confirm
earlier reports of improved gait in PD. Although progressive deterioration of
axial motor symptoms occur with DBS of the STN or GPi, new preliminary research
suggests that other surgical stimulation sites, such as the PPN, may have a
potential benefit on gait and balance impairments in PD. Ongoing vigorous
exercise and physical fitness should be highly encouraged to patients with PD who
are at risk of physical deconditioning and fear of falling but effective anti
fall physical therapy interventions remain an unmet clinical need.
PMID- 24348753
TI - Photo-Reactive Nanogel as a Means to Tune Properties during Polymer Network
Formation.
AB - Photo-reactive nanogels with an integrated photoinitiator-based functionality
were synthesized via a Reversible Addition-Fragmentation Chain Transfer (RAFT)
process. Without additional free initiators, this nanogel is capable of radical
generation and initiating polymerization of a secondary monomer (i.e.
dimethacrylate) that infiltrates and disperses the nanogel particles. Due to the
presence of RAFT functionality and the fact that all initiating sites are
initially located within the nanogel structure, gelation can be delayed by
sequencing the polymerization from the nanogel to the bulk matrix. During
polymerization of a nanogel-filled resin system, a progressive delay of gelation
conversion from about 2 % for conventional chain growth polymerization to 18 %
for the same monomer containing 20 wt% nanogel additive was achieved. A
significant delay of stress development was also observed with much lower final
stress achieved with the nanogel-modified systems due to the change of network
formation mechanics. Compared with the nanogel-free dimethacrylate control, which
contained uniformly distributed free initiator, the flexural modulus and
mechanical strength results were maintained for the photopolymers with nanogel
contents greater than 10 wt%. There appears to be a critical interparticle
spacing of the photo-reactive nanogel that provides effective photopolymerization
while providing delayed gelation and substantial stress reduction.
PMID- 24348754
TI - Human papillomavirus oncoproteins and apoptosis (Review).
AB - The aim of this study was to review the literature and identify the association
between human papillomavirus (HPV) oncoproteins and apoptosis. HPV-associated
apoptosis may be primarily blocked by a number of oncoproteins, including E5, E6
and E7. E5 protein protects cells from tumor necrosis factor-associated
apoptosis; the oncoprotein E6 predominantly inhibits apoptosis through the p53
pathway; and oncoprotein E7 is involved in apoptosis activation and inhibition.
In addition, HPV oncoproteins are involved in activating or repressing the
transcription of E6/E7. In conclusion, HPV oncoproteins, including E5, E6 and E7
protein, may interfere with apoptosis via certain regulatory principles.
PMID- 24348755
TI - Pancreaticobiliary maljuction combining with pancreas divisum: Report of four
cases.
AB - Pancreaticobiliary maljunction (PBM) is an unusual anomalous condition in which
the pancreatic duct and bile duct merge outside the duodenal wall and form a long
common channel. Pancreas divisum (PD) is a congenital anomaly in which the dorsal
and ventral pancreatic ducts fail to fuse. Endoscopic retrograde
cholangiopancreatography (ERCP) is the gold standard for diagnosing PD and
magnetic resonance cholangiopancreatography (MRCP) is the non-invasive choice. In
this study, four cases of patients with unusual PBM in addition to PD are
described. The patients presented with abdominal pain, which was caused by distal
biliary stricture diagnosed by MRCP. The patients received ERCP and had a good
prognosis.
PMID- 24348757
TI - Mechanisms of the immunosuppressive effects of mouse adipose tissue-derived
mesenchymal stromal cells on mouse alloreactively stimulated spleen cells.
AB - The mechanisms of immunomodulation by mesenchymal stromal cells remain poorly
understood. In this study, the effects of mouse adipose tissue-derived
mesenchymal stromal cells (ASCs) on mouse spleen cells alloreactively stimulated
by anti-CD3 and anti-CD28 antibody-coated (anti-CD3/CD28) beads were observed.
Production of interferon-gamma by the anti-CD3/CD28 bead-stimulated spleen cells
was significantly suppressed in co-culture with ASCs. However, an augmented
intensity of CD69 on the stimulated spleen cells was not suppressed in the
presence of ASCs. The immunosuppressive effects of ASCs were partially mediated
by one or more soluble factors (26% suppression). However, the ASCs require cell
cell contact in order to maximally exert suppression (88%). The suppressive
effect of ASCs mediated by direct cell contact was partially reversed following
knockdown of beta2 microglobulin, a component of the major histocompatibility
complex (MHC) class I molecule, with siRNA. The results of the study demonstrated
that ASCs have significant immune modulatory effects on alloreactively stimulated
spleen cells. The effects of ASCs on spleen cells are dependent on soluble
factor(s) and cell contact, which is mediated by the MHC class I complex on ASCs.
PMID- 24348756
TI - Protective effect of the ultra-filtration extract from Xin Mai Jia on human
aortic smooth muscle cell injury induced by hydrogen peroxide.
AB - The aim of the present study was to explore whether an ultra-filtration extract
from Xin Mai Jia (XMJ), a Chinese medicinal formulation, has a protective effect
on human aortic smooth muscle cell (HASMC) injury models induced by hydrogen
peroxide (H2O2), and to consider the mechanism and efficacy of the therapeutic
action of XMJ on atherosclerosis. HASMCs were injured by H2O2 and then exposed to
various concentrations of XMJ. The morphological changes, growth, proliferation,
migration and cytokine release of HASMCs were detected using 2,3-bis-(2-methoxy-4
nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), an enzyme-linked
immunosorbent assay and a scratch adhesion test. H2O2 significantly promoted the
proliferation of HASMCs. The ultra-filtration extract from XMJ was observed to
significantly attenuate the morphological changes of injured HASMCs, reduce the
expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell
adhesion molecule-1 (VCAM-1), interleukin (IL)-1, IL-6 and nuclear factor (NF)
kappaB, and increase the expression levels of matrix metalloproteinase (MMP)-2
and tissue inhibitor of metalloproteinase (TIMP). XMJ has clear anti-inflammatory
and antioxidant effects, and significantly inhibits the proliferation and
migration of HASMCs.
PMID- 24348758
TI - Quantitative analysis of vascular calcification.
AB - Vascular calcification is a prominent feature of atherosclerosis. The mineral
composition and quantity within calcified arterial plaques remains unelucidated;
therefore, the aim of this study was to analyze the mineral composition of such
plaques. Calcified arterial plaques were obtained from patients with abdominal
aortic aneurysms (AAAs) and carotid artery stenoses. Calcified aneurysmal plaques
were obtained during the routine open repair of AAAs, while calcified carotid
plaques were collected from patients who underwent carotid endarterectomy (CEA).
Following the appropriate preparation of each sample, inductively coupled plasma
atomic emission spectrometry (ICP-AES) was used to analyze the calcium and
phosphate levels, while flame atomic absorption spectrometry (FAAS) was used to
analyze the levels of iron and zinc. The levels of these mineral components were
evaluated. In the aortic and carotid plaques, the mean calcium concentration was
9.83 and 11.94 wt.%, respectively, and the mean phosphate concentration was 4.31
and 6.08 wt.%, respectively. It was not possible to analyze the absolute
concentration of iron in the carotid plaques due to the concentration being below
the measurement limit. The zinc concentration was variable between samples. In
conclusion, the main components of aortic and carotid plaques are calcium and
phosphate. The mineral concentrations of the plaques in the present study may be
used as reference values for further studies on vascular calcification. More
studies are required to elucidate the correlation between the mineral components
and vascular calcification.
PMID- 24348759
TI - Efficacy of once or twice weekly administration of epoetin kappa in patients
receiving hemodialysis: A retrospective study.
AB - Several clinically approved recombinant erythropoietin (rEPO) preparations, such
as epoetin-beta, epoetin-delta and the epoetin-alpha derivative, darbepoetin
alpha, have been commercially produced. Since the expiration of patent
protection, a number of novel rEPO biosimilars have been approved on the world
market. In 2010, epoetin-kappa, which is biosimilar to epoetin-alpha, was
clinically approved. Epoetin-kappa is a biopharmaceutical product that is based
on serum-free media following master cell bank preparation. The present study
analyzes the results obtained during a six-month observation period, in which the
administration of epoetin-beta was switched to that of epoetin-kappa. In a cohort
of patients receiving chronic dialysis, who were clinically in a state of
relative calm and were in control of their renal anemia, it was possible to
sustain good control of the anemia by reducing the frequency of the epoetin-beta
administration from the conventional and empirically determined three times a
week to twice a week, and further to once a week. Furthermore, the good control
was maintained upon changing from the administration of epoetin-beta to that of
epoetin-kappa. Moreover, three months subsequent to this switch, the degree of
instability observed among the patients had decreased. Despite the fact that the
situation following the changeover requires further investigation, it may be
concluded that the results obtained in this study are indicative of the clinical
equivalence and efficacy of epoetin-kappa.
PMID- 24348760
TI - Null anticarcinogenic effect of silymarin on diethylnitrosamine-induced
hepatocarcinogenesis in rats.
AB - The aim of this study was to investigate the anticarcinogenic effects of
silymarin in diethylnitrosamine (DEN)-induced hepatocarcinogenic rat models.
Severe and mild models of hepatocellular carcinoma (HCC) were generated by the
intraperitoneal administration of 40 mg/kg DEN once a week for 18 weeks and 100
mg/kg DEN every 2 weeks for 6 weeks in male Wistar rats, respectively. In the
severe and mild models of HCC, the rats were treated with 0.1 and 0.5% silymarin
for 18 weeks and with 0.1% silymarin for 5 weeks, respectively. Serum
transaminase levels were not significantly decreased by the silymarin treatment
in either model. Macroscopic and microscopic features indicated that the
silymarin-containing formulations did not significantly inhibit the hepatic tumor
formation induced by DEN. Furthermore, immunohistochemical and western blot
analyses demonstrated that the expression levels of proliferating cell nuclear
antigen and glutathione S-transferase P, which are hepatocarcinogenic markers,
were not significantly modified by the silymarin treatment. These results
indicate that silymarin may not be considered as a candidate agent against
hepatocarcinogenesis.
PMID- 24348762
TI - A comparison of oxytocin and carboprost tromethamine in the prevention of
postpartum hemorrhage in high-risk patients undergoing cesarean delivery.
AB - The aim of this study was to compare carboprost with oxytocin for the prevention
of postpartum hemorrhage (PPH) in females with a high risk of PPH undergoing
cesarean delivery. Patients were randomly divided into three groups that received
different uterotonics (oxytocin, carboprost and oxytocin plus carboprost) during
cesarean section, following the delivery of the infant. A total of 117 females
(age range, 19-40 years) at 35-40 weeks gestation who delivered by cesarean
between December, 2010 and May, 2012 were included in this study. There were 29
cases of twins, 12 cases of polyhydramnios, 23 cases of placenta previa and 53
cases of fetal macrosomia. There were 37 patients in the oxytocin group, 36 in
the carboprost group and 44 in the oxytocin plus carboprost group. No significant
differences were identified in maternal age, gravidity/parity, gestational age
and reason for cesarean delivery between the three groups. The median blood loss
in the oxytocin, carboprost and oxytocin plus carboprost groups was 610, 438 and
520 ml, respectively. The blood loss in the carboprost group was significantly
lower than that in the oxytocin and oxytocin plus carboprost groups (both
P<0.05). Vomiting occurred in eight patients from the carboprost group, two from
the oxytocin group and two from the oxytocin plus carboprost group (P=0.036).
Carboprost was more effective than oxytocin in preventing PPH in high-risk
patients undergoing cesarean delivery.
PMID- 24348761
TI - Pyrrolidine dithiocarbamate (PDTC) inhibits the overexpression of MCP-1 and
attenuates microglial activation in the hippocampus of a pilocarpine-induced
status epilepticus rat model.
AB - The aim of this study was to investigate the effects of pyrrolidine
dithiocarbamate (PDTC) on MCP-1 expression and microglial activation in the
hippocampus of a rat model of pilocarpine (PILO)-induced status epilepticus (SE).
Moreover, seizure susceptibility, frequency and severity as well as brain damage
were analyzed and changes in behavior were recorded. Chemokine MCP-1 expression
and microglial activation were detected by immunohistochemistry (IHC). Fluoro
Jade C (FJC) and NeuN staining were used for the evaluation of tissue damage. Our
results showed that although SE resulted in the upregulation of MCP-1 and
microglial activation in the rat hippocampus 24 h after seizure onset,
pretreatment with PDTC significantly inhibited the MCP-1 overexpression and
attenuated the microglial activation. These effects were accompanied by
neurodegenerative amelioration. To the best of our knowledge, these findings
indicated for the first time that the activation of the nuclear factor-kappaB (NF
kappaB) pathway may contribute to MCP-1 upregulation and microglial activation in
the context of epilepsy. PDTC was also shown to exert anticonvulsant activity and
to have a neuroprotective effect on the hippocampal CA1 and CA3 regions,
potentially through attenuating microglial activation.
PMID- 24348763
TI - A novel technique for central hepatectomy: Maintain the blood supply and biliary
drainage on one side and the blood supply from the portal vein on the other.
AB - Central hepatectomy is amongst the most difficult surgeries of liver tumors. For
the routine local excision of a tumor, if the tumor has invaded the blood vessels
or bile duct of the liver, then half of the liver or three lobes of the liver are
resected. This results in two major drawbacks, one of which is that the residual
hepatic lobe may not compensate for the damage, so it is not possible to perform
conventional partial resection. The other is that the volume of normal liver
tissue removed may be much more than the volume of tumor removed, causing
substantial waste. In the present study, surgery was performed to resect a
central liver tumor. In that surgery, the V segment and parts of the IV, VI and
VIII segments were resected, and the blood supply and biliary drainage of the
left hepatic lobe were kept intact. However, for the remaining VI, VII and VIII
segments of the right hepatic lobe, only the blood supply from the portal vein
was maintained and no arterial blood supply or biliary drainage was kept so that
the patient had the opportunity to undergo radical resection and successful
rehabilitation. The reason these opportunities may be possible is that the
residual right liver is a temporary replacement therapy in the perioperative
period. Therefore, for central hepatic tumors, particularly tumors that have
invaded the neighboring bile ducts or blood vessels, if the blood supply and
biliary drainage on one side is maintained and the blood supply to the other side
from the portal vein is kept intact, then it is possible to perform radical
resection. This provides a novel approach to the clinical resection of central
liver tumors.
PMID- 24348765
TI - Intractable epilepsy due to angiocentric glioma: A case report and minireview.
AB - The aim of this case report and minireview was to investigate the diagnosis of
and therapeutic approaches for angiocentric glioma (AG) and to summarize the
clinical manifestations and the pathological and imaging characteristics of the
disease. Intraoperative cortical electroencephalogram (ECoG) monitoring was
performed to locate the epileptic foci in a child with AG who presented with
intractable epilepsy, prior to the total resection of the tumor being performed
under the microscope. The clinical features, imaging characteristics,
intraoperative conditions, surgical methods and pathological results were
analyzed and compared with the literature. The review revealed that to date, the
clinical features of the 52 reported cases of AG (including this case) have been
mainly characterized by epilepsy. High T2-weighted image (WI) and fluid
attenuated inversion recovery (FLAIR) signals may be detected with magnetic
resonance imaging (MRI) scanning of the cranium; however, no enhancement signals
are detected by enhanced scanning. The prognosis following surgical resection is
favorable. The lesions in the present case demonstrated clear boundaries with a
central cystic affection accompanied by an arachnoid cyst on the left temporal
pole. Pathological examination revealed that the lesion was positive for glial
fibrillary acidic protein (GFAP), S-100 protein, vimentin, epithelial membrane
antigen (EMA), cluster of differentiation 99 (CD99) and D2-40. The Ki-67/MIBk-1
labeling index was ~1%. In conclusion, AG exhibits characteristic features in
imaging; however, its diagnosis depends on histopathological examination. The
prognosis of total surgical resection is good and intraoperative ECoG may be used
to assist positioning.
PMID- 24348764
TI - Stimulation of the proliferation of human normal esophageal epithelial cells by
fumonisin B1 and its mechanism.
AB - Previous epidemiological studies have demonstrated a correlation between
fumonisin B1 (FB1) and human esophageal cancer in China, Iran and South Africa.
The purpose of this study was to investigate the effects of FB1 on the
proliferation, cell-cycle and apoptosis of normal human esophageal epithelial
cells (HEECs) and to explore the molecular mechanisms of these effects. The
proliferation of HEECs treated with FB1 was assessed using a colorimetric assay,
while analyses of the cell cycle and apoptosis were performed using flow
cytometry and the measurement of the protein expressions of genes associated with
the cell cycle was conducted using western blotting. The results showed that FB1
stimulated the proliferation of HEECs, decreased the percentage of cells in the
G0/G1 phase and reduced apoptosis. The western blotting results showed that FB1
significantly increased the protein expression of cyclin D1 and significantly
decreased the protein expression of cyclin E, p21 and p27. The results indicated
that FB1 stimulated the proliferation of HEECs by affecting the cell cycle and
apoptosis. This mechanism was associated with changes in cyclin D1, cyclin E, p21
and p27 expression.
PMID- 24348766
TI - MEK inhibition reduces glial scar formation and promotes the recovery of
sensorimotor function in rats following spinal cord injury.
AB - The aim of this study was to investigate the effect of U0126 on the formation of
glial scars following spinal cord injury (SCI) in a rat model. Ninety adult
female Sprague-Dawley rats were divided randomly into sham injury (group I), SCI
(group II) and U0126 treatment (group III) groups, and functional outcome was
observed during the 4 weeks following the injury. The P1 and N1 latencies and P1
N1 amplitudes of somatosensory-evoked potentials (SEPs) were collected one day
prior to surgery, on the day of surgery and 14 and 28 days postoperatively. The
expression levels of glial fibrillary acidic protein (GFAP) and vimentin (Vim)
were assessed 14 and 28 days post-injury. Treatment with U0126 significantly
increased locomotor function from the second week until 4 weeks post-SCI. At 14
and 28 days subsequent to the injury, the number of cells that were positive for
GFAP expression in the U0126-treated group was significantly reduced and the GFAP
positive cells were observed to be smaller, with a reduced prominence and pale
staining. Moreover, the area of glial scarring was smaller compared with that of
the SCI controls. Inhibitors of MEK may reduce glial scar formation by
suppressing the proliferation of astrocytes, and may improve hindlimb motor
function.
PMID- 24348767
TI - Analysis of mitochondrial transcription factor A SNPs in alcoholic cirrhosis.
AB - Genetic susceptibility to alcoholic cirrhosis (AC) exists. We previously
demonstrated hepatic mitochondrial DNA (mtDNA) damage in patients with AC
compared with chronic alcoholics without cirrhosis. Mitochondrial transcription
factor A (mtTFA) is central to mtDNA expression regulation and repair; however,
it is unclear whether there are specific mtTFA single nucleotide polymorphisms
(SNPs) in patients with AC and whether they affect mtDNA repair. In the present
study, we screened mtTFA SNPs in patients with AC and analyzed their impact on
the copy number of mtDNA in AC. A total of 50 patients with AC, 50 alcoholics
without AC and 50 normal subjects were enrolled in the study. SNPs of full-length
mtTFA were analyzed using the polymerase chain reaction (PCR) combined with gene
sequencing. The hepatic mtTFA mRNA and mtDNA copy numbers were measured using
quantitative PCR (qPCR), and mtTFA protein was measured using western blot
analysis. A total of 18 mtTFA SNPs specific to patients with AC with frequencies
>10% were identified. Two were located in the coding region and 16 were
identified in non-coding regions. Conversely, there were five SNPs that were only
present in patients with AC and normal subjects and had a frequency >10%. In the
AC group, the hepatic mtTFA mRNA and protein levels were significantly lower than
those in the other two groups. Moreover, the hepatic mtDNA copy number was
significantly lower in the AC group than in the controls and alcoholics without
AC. Based on these data, we conclude that AC-specific mtTFA SNPs may be
responsible for the observed reductions in mtTFA mRNA, protein levels and mtDNA
copy number and they may also increase the susceptibility to AC.
PMID- 24348768
TI - Effects of Porphyromonas gingivalis lipopolysaccharide on osteoblast-osteoclast
bidirectional EphB4-EphrinB2 signaling.
AB - In bone remodeling, the Eph family is involved in regulating the process of
osteoclast and osteoblast coordination in order to maintain bone homeostasis. In
this study, the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS)
on the osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling were
investigated. An osteoblast-osteoclast co-culture system was achieved
successfully. Hence, direct contact and communication between osteoblasts and
osteoclasts was permitted. Regarding the protein expression and gene expression
of EphB4 and EphrinB2, it was shown that Pg-LPS increased the expression of EphB4
while inhibiting the expression of EphrinB2. Therefore, the results indicate
that, when treated with Pg-LPS, the EphB4 receptor on osteoblasts and the
EphrinB2 ligand on osteoclasts may generate bidirectional anti-osteoclastogenic
and pro-osteoblastogenic signaling into respective cells and potentially
facilitate the transition from bone resorption to bone formation. This study may
contribute to the control of osteoblast differentiation and bone formation at
remodeling, and possibly also modeling, sites.
PMID- 24348770
TI - Solitary schwannoma of the sural nerve: An unusual clinical presentation.
AB - Schwannomas may arise from any peripheral nerve containing Schwann cells.
However, sural nerve schwannoma is extremely rare. In this study, a case of
solitary schwannoma originating from the sural nerve in a 42-year-old male is
presented. Physical examination revealed a 3-cm, elastic-hard, mobile, non-tender
mass, while neurovascular examinations, including Tinel's sign, were normal.
Magnetic resonance imaging revealed an oval-shaped subcutaneous mass with iso
signal intensity relative to skeletal muscle on T1-weighted sequences. T2
weighted spectral presaturation with inversion recovery sequences showed higher
signal intensity peripherally and lower signal intensity centrally, representing
a target sign. Contrast-enhanced T1-weighted sequences demonstrated a marked
central enhancement of the mass. The tumor was completely enucleated using an
intracapsular technique. Histological examination confirmed the diagnosis of a
schwannoma, consisting mainly of Antoni A tissue. The patient had no evidence of
local recurrence and no neurological deficit at the final follow-up. Although
rare, schwannoma should be considered in the differential diagnosis of a well
defined, oval, subcutaneous mass in the posterior aspect of the lower leg.
PMID- 24348769
TI - Correlation of fibrinogen-like protein 2 with disease progression in patients
with severe acute pancreatitis.
AB - It has recently been demonstrated that fibrinogen-like protein 2 (fgl2) is
expressed on the surface of macrophages, T cells and endothelial cells and
directly cleaves prothrombin to thrombin. The present study was designed to
examine fgl2 expression in patients with severe acute pancreatitis (SAP) and its
correlation with disease progression. Peripheral blood mononuclear cells (PBMCs)
were isolated from 25 patients with SAP, 37 patients with mild acute pancreatitis
(MAP) and 20 healthy volunteers as controls. Paraffin sections of pancreas were
obtained from 18 postoperative patients with SAP between 2003 and 2012. Human
fgl2 (hfgl2) gene expression was determined in the PBMCs by real-time PCR. A
monoclonal antibody against hfgl2 was applied to detect hfgl2 protein expression
in the pancreatic tissues as well as in the PBMCs by immunohistochemical
staining. The levels of hfgl2 expression in the PBMCs from the 25 patients with
SAP were markedly upregulated compared with the other groups, whereas no
significant difference between the MAP group and healthy controls was observed.
hfgl2 expression in the PBMCs and pancreatic tissues was detectable through using
immunohistochemistry and was demonstrated to be specifically localized to the
endothelium of microvessels and inflammatory infiltrative cells in the areas of
acute focal, confluent necrosis. There were positive correlations between hfgl2
expression in the PBMCs and the severity of SAP, as indicated by scores of Ranson
and Acute Physiology and Chronic Health Evaluation II. The results suggest that
hfgl2 is involved in the pathogenesis of SAP and hfgl2 levels may serve as a
biomarker during disease progression.
PMID- 24348771
TI - Establishment and primary clinical application of competitive inhibition for
measurement of augmenter of liver regeneration.
AB - The aim of the present study was to establish a quantitative method for the
measurement of serum human augmenter of liver regeneration (hALR) using
competitive inhibition that is applicable in the clinic. A monoclonal antibody to
hALR was used as the primary antibody and the pure hALR protein was used as a
standard for competition with Eu3+-labeled hALR (Eu3+-hALR) to plot a standard
curve. Serum samples from 90 patients with various liver diseases due to
hepatitis B virus (HBV) infection were used for a competitive reaction with Eu3+
hALR. A regression analysis of the results was performed using the standard curve
to calculate the serum concentration of hALR. The minimum detectable value using
direct competitive measurement established by Eu3+-hALR was 1 ng/ml, with a
positive linear correlation within the range of 200 ng/ml. In the sera of the 90
patients, the hALR level in the severe hepatitis group was the highest, followed
by that in the acute hepatitis group. The serum hALR levels in the cirrhosis and
chronic hepatitis groups were significantly higher compared with those in the
normal control groups (P<0.01). The direct competitive measurement method of
serum hALR established in the present study has high sensitivity, specificity,
stability and reliability, meets clinical requirements and may be used as
potential index in clinical tests.
PMID- 24348772
TI - Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A
retrospective study.
AB - Acute fulminant myocarditis (AFM) is a serious heart disease with limited
treatment. This observational retrospective study aimed to investigate whether
intravenous immunoglobulin (IVIG) was able to improve left ventricular function
and reduce the episodes of arrhythmia in adult patients with AFM. The medical
records of all patients with AFM who were admitted to the Critical Care Unit of
Guangdong General Hospital (Guangzhou, China) between January 2001 and December
2010 were reviewed. A cohort of 58 patients was included in the study. Of these
58, 32 patients were treated with IVIG (400 mg/kg per day) for five days, while
the remaining patients did not receive IVIG therapy. The patients who received
IVIG therapy had a higher left ventricular ejection fraction (LVEF) and a reduced
left ventricular end-diastolic diameter (LVDD) compared with the non-IVIG therapy
patients four weeks subsequent to the treatment (PLVEF=0.011 and PLVDD=0.048).
The post-treatment incidence of ventricular tachycardia/ventricular fibrillation
(VT/VF) and atrioventricular block (AVB) was reduced in the patients who received
IVIG therapy compared with the baseline values (PVT/VF=0.025, PAVB=0.003);
however, no significant differences were observed in the non-IVIG therapy
patients (PVT/VF=0.564, PAVB=0.083) following treatment. There were two
mortalities in the IVIG therapy group and seven in the non-IVIG therapy group
(P=0.072). This retrospective study suggested that the use of IVIG for the
treatment of AFM may be associated with improved left ventricular function and
reduced episodes of fulminant arrhythmias.
PMID- 24348773
TI - Thrombolytic and anticoagulant therapy for acute submassive pulmonary embolism.
AB - This study aimed to compare the efficacy and safety of thrombolytic and
anticoagulant therapy for acute submassive pulmonary embolism (PE). A
retrospective evaluation was performed on 25 consecutive inpatients with acute
submassive PE treated by thrombolytic therapy and 25 earlier consecutive
inpatients with acute submassive PE treated by anticoagulant therapy. No
statistically significant difference in clinical curative effect was identified
between the thrombolysis and anticoagulation groups (P>0.05). Following 24 h of
therapy, the improvement rates of dyspnea and revascularization in the
thrombolysis group achieved statistical significance compared with those of the
anticoagulation group (P<0.01 for each). The PO2 level of the thrombolysis group
(81.18+/-5.66 mmHg) was notably higher than that of the anticoagulation group and
the difference was statistically significant (P<0.01). The pulmonary arterial
pressures of the thrombolysis group (51.21+/-6.86 mmHg) were significantly lower
than those of the anticoagulation group (60.64+/-5.17 mmHg) (P<0.01).
Furthermore, the difference between the hemorrhage rates of the two groups was
statistically significant (P<0.05). Thrombolysis was shown to rapidly relieve
dyspnea, reduce pulmonary arterial pressure and revascularize the embolized blood
vessels. However, the hemorrhage rate of the thrombolysis group was higher than
that of the anticoagulation group. The overall efficacies and fatality rates of
the thrombolysis and anticoagulation groups were similar.
PMID- 24348774
TI - Alpinetin activates the delta receptor instead of the kappa and MU receptor
pathways to protect against rat myocardial cell apoptosis.
AB - Alpinetin is a natural flavonoid that protects cells against fatal injury in
ischemia-reperfusion. delta receptor activation protects myocardial cells from
trauma; however, the mechanism is unknown. The aim of this study was to explore
the function of alpinetin in delta receptor-mediated myocardial apoptosis. The
myocardial cells of newly born rats were cultivated and myocardial apoptosis was
induced by serum deprivation. The MTT method was used to evaluate cell viability
and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining
was used to analyze apoptosis. The expression levels of opioid receptor mRNA and
protein were tested using reverse transcription-polymerase reaction (RT-PCR) and
western blot assays. In addition, an opioid receptor antagonist, as well as
protein kinase C (PKC) and extracellular signal-regulated kinase (ERK)
inhibitors, were used to determine the inferred signaling pathway. The results
showed that that alpinetin reduced the myocardial apoptosis induced by serum
deprivation in a concentration-dependent manner. However, the protection
conferred to the myocardial cells by alpinetin was blocked by the delta opioid
receptor antagonist naltrindole, as well as by PKC and ERK inhibitors (GF109203X
and U0126, respectively). In addition, it was shown that alpinetin was able to
maintain the stability of the mitochondrial membrane potential, lower the level
of intracytoplasmic cytochrome c and reduce Bax displacement from the cytoplasm
to the mitochondria. It was concluded that alpinetin was able to activate delta
receptors to induce the endogenous protection of myocardial cells via the PKC/ERK
signaling pathway.
PMID- 24348775
TI - Postconditioning with rosuvastatin reduces myocardial ischemia-reperfusion injury
by inhibiting high mobility group box 1 protein expression.
AB - High mobility group box 1 protein (HMGB1) plays an important role in myocardial
ischemia-reperfusion (I/R) injury. Rosuvastatin (RS) preconditioning has been
reported to reduce myocardial I/R injury. The aim of this study was to
investigate whether postconditioning with RS is able to reduce myocardial I/R
injury by inhibiting HMGB1 expression in rats. Anesthetized male rats were
subjected to ischemia for 30 min and treated once with RS (10 mg/kg, i.v.) 5 min
prior to reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK)
and superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and
infarct size were measured. HMGB1 expression was assessed by immunoblotting. The
results showed that RS postconditioning significantly decreased the infarct size
and the activities of LDH and CK following 4 h reperfusion (all P<0.05). RS
postconditioning also significantly inhibited the increase of MDA levels and the
reduction of SOD activity (both P<0.05). RS postconditioning was able to
significantly inhibit the HMGB1 expression induced by I/R. The present study
suggested that postconditioning with RS reduces myocardial I/R injury, which may
be associated with the inhibition of HMGB1 expression.
PMID- 24348776
TI - A study exploring critical pathways in clear cell renal cell carcinoma.
AB - Renal cell carcinoma (RCC) is the most lethal type of cancer in the urinary
system and often presents as a metastatic disease. Furthermore, there are no
effective treatments for the disease. Several studies based on gene expression
profiling have been performed with the aim of gaining insights into the
pathogenesis of RCC; however, few studies have investigated RCC at the pathway
level to search for the possible pathways involved in clear cell RCC (CCRCC). In
this study, gene set enrichment analysis (GSEA) was conducted on microarray
datasets from CCRCC tissue. DAVID functional enrichment analysis was performed
based on the dysregulated genes that were identified in a meta-analysis performed
on the microarray datasets from CCRCC tissue. In GSEA, 17 down- and 12
upregulated pathways coexisted in six datasets. The majority of the upregulated
pathways were associated with the immune system. In addition, 32 dysregulated
pathways were obtained from DAVID functional enrichment analysis, based on the
abnormal genes identified by meta-analysis. This study demonstrated that cross
GSEA is a useful method for exploring the critical pathways involved CCRCC;
however, an individual dataset with a small sample may introduce bias. A cross
GSEA based on certain well-designed datasets may be required to further the
progress made in this study, following the analysis of its results.
PMID- 24348777
TI - Evaluation of the revised versus the simplified scoring system in patients with
autoimmune hepatitis.
AB - The aim of this study was to evaluate the simplified and revised scoring systems
for the diagnosis of autoimmune hepatitis (AIH). Seventy-seven patients diagnosed
with AIH via the revised scoring system were enrolled in this study. Statistical
analysis was performed by means of the chi2 test and logistic regression
analysis. A total of 39 patients with definite AIH and 38 patients with probable
AIH were diagnosed by the revised scoring system, whereas among these 77
patients, the simplified scoring system classified nine cases as definite AIH, 39
as probable AIH and 29 without AIH. In this study, the parameters contributing to
the discrepant diagnosis of AIH were compared using the revised and simplified
systems. A chi2 test showed that antinuclear antibody (ANA) or smooth muscle
antibody (SMA) titers were significantly lower in the patients with discrepant
diagnoses (chi2=15.0, P=0.001). Logistic regression with backward selection
revealed that for the discrepant diagnosis of patients, the presence of other
concurrent autoimmune diseases [odds ratio (OR)=7.25; P=0.018; 95% confidence
interval (CI), 1.41-37.29] was the only independent risk factor. In addition, the
presence of anti-soluble liver antigen/liver-pancreas antigen (SLA/LP) or
perinuclear antineutrophil cytoplasmic antibody (pANCA) (OR=0.12; P=0.022; 95%
CI, 0.02-0.74), the level of immunoglobulin G (IgG) with 1-1.1 * Normal (N)
(OR=0.02; P=0.044; 95% CI, 0.00-0.89) and ANA or SMA titers >=1:80 (OR=0.04;
P=<0.001; 95% CI, 0.01-0.23) were three independent protective factors. In
conclusion, the revised scoring system has a superior performance in the
diagnosis of patients with AIH compared with the simplified scoring system.
According to the simplified scoring system, other concurrent autoimmune diseases
are the risk factor for the AIH diagnosis.
PMID- 24348778
TI - Changes in monoclonal HLA-DR antigen expression in acute organophosphorus
pesticide-poisoned patients.
AB - The aim of this study was to investigate changes in human leukocyte antigen (HLA)
DR expression of peripheral blood mononuclear cells (MNCs) in patients with acute
organophosphorus pesticide poisoning (AOPP). HLA-DR antigen expression of
peripheral blood MNCs was examined in 75 patients with AOPP, including 36
patients without multiple organ dysfunction syndrome (non-MODS) and 39 patients
with multiple organ dysfunction syndrome (MODS), as well as in 30 healthy
individuals using flow cytometry assay. The associations between HLA-DR antigen
expression and certain parameters were analyzed, including acute physiology and
chronic health evaluation II (APACHE II) score, serum cholinesterase (ChE)
activity, cardiac troponin I (cTnI), cardiac enzymes, and liver and kidney
function. The mean fluorescence intensity (MCF) of HLA-DR expression in the AOPP
group (21.59+/-5.36) was significantly lower than that in the control group
(27.85+/-4.86) (P<0.001). The MCF in the MODS group (18.17+/-4.23) was lower than
that in the non-MODS group (25.15+/-6.15). In addition, the MCF of the deceased
patients (15.29+/-3.97) was lower than that of the surviving patients (22.34+/
2.76) (P<0.001). The MCF of patients with AOPP and MODS was positively correlated
with serum ChE (P<0.01) and negatively correlated with the APACHE II score,
creatine kinase isoenzyme, cTnI, lactate dehydrogenase, alanine aminotransferase,
aspartate aminotransferase, blood urea nitrogen and serum creatinine (P<0.05). In
conclusion, HLA-DR expression in patients with AOPP was significantly decreased
compared with that in healthy individuals; HLA-DR expression may therefore be a
good indicator for evaluating AOPP, MODS disease severity, immune function,
efficacy of prognosis and prognosis. Examination of HLA-DR antigen expression may
be of crucial clinical value.
PMID- 24348779
TI - A case of veno-occlusive disease following liver transplantation.
AB - The present case report describes the diagnosis and treatment of a patient with
veno-occlusive disease (VOD) following liver transplantation. Combining the
clinical data and relevant literature, the study aimed to consider the causes of
VOD following liver transplantation, and the pathogenesis, clinical diagnosis and
auxiliary examination features of VOD. A 42-year-old man who had a long history
of taking traditional Chinese medicine (essential components unknown) underwent
an orthotropic liver transplantation on January 14, 2011, due to small venous
occlusion disease of the liver. The patient was treated with tacrolimus as an
antirejection therapy following the surgery, and gradually developed right upper
quadrant pain and fatigue. The examination results were consistent with the
diagnostic standards for VOD. Following treatment with methylprednisolone, the
patient was treated with alprostadil and Danhong injections. Forty days later,
the patient's total bilirubin (TBIL) level was observed to have decreased
significantly, the liver function had returned to normal and the ascites had
decreased, but had not completely disappeared. The patient then underwent a
transjugular intrahepatic portosystemic shunt (TIPS) procedure, following which
the ascites were shown to have completely disappeared.
PMID- 24348780
TI - Clinical features in different age groups of patients with autoimmune hepatitis.
AB - The Chinese population are at an increased risk of autoimmune hepatitis (AIH).
The aims of this study were to determine the demographic and clinical features of
AIH in China. A total of 83 patients with AIH diagnosed by the revised scoring
system were re-analyzed, and the clinical presentations among the different ages
were compared. The patients were classified according to age at presentation. AIH
occurred in patients aged <=30 years (9.6%), 31-39 years (10.8%), 40-49 years
(16.9%), 50-59 years (31.3%) and >=60 years (31.3%). There were no differences in
the form of the clinical presentation, concurrent autoimmune diseases, cirrhosis
distribution and autoantibodies among the groups. However, patients aged >=60
years presented with higher levels of alkaline phosphatase (ALP) and gamma
glutamyl transpeptidase (gamma-GT) compared with patients aged <=30 years
(P=0.034, P=0.043, respectively), and patients aged 31-39 years had a
significantly lower immunoglobulin G (IgG) level compared with those aged 50-59
years (P=0.049) and those aged >=60 years (P=0.012). By contrast, patients aged
<=30 years had a significantly higher total bilirubin (TBIL) level compared with
those aged 31-39 years (P=0.007), 50-59 years (P=0.002) and >=60 years (P=0.013).
A substantial portion of patients with AIH were aged >60 years, indicating a poor
liver-associated outcome under current management strategies. Elderly patients
appeared to be more asymptomatic compared with the younger patients.
PMID- 24348781
TI - Elevated NKT cell levels in adults with severe chronic immune thrombocytopenia.
AB - The aim of this study was to investigate the frequency of circulating natural
killer T (NKT) cells and regulatory T cells (Tregs), as well as serum cytokine
profiles, in adult chronic primary immune thrombocytopenia (ITP). The frequency
of circulating T cell receptor (TCR) Valpha24+Vbeta11+CD3+ NKT cells and
CD4+CD25+CD127-/low Tregs was measured using multi-color flow cytometry. The
serum concentrations of 11 cytokines were determined with a cytometric bead
assay. The frequency of circulating NKT cells in patients with ITP was 0.13+/
0.03%, whereas the frequency in healthy controls was 0.07+/-0.01% of CD3+
(P>0.05). However, the frequency of NKT cells in patients with ITP with platelet
counts <=20*109/l (0.22+/-0.05%) was significantly higher than that in patients
with platelet counts >20*109/l (0.05+/-0.01%; P<0.05) and that in healthy
controls (0.07+/-0.01%; P<0.05). The frequency of peripheral Tregs was comparable
between patients with ITP (3.97+/-0.44% of CD4+) and healthy controls (3.69+/
0.31%; P>0.05). No significant differences were observed in the serum
concentrations of 11 cytokines between patients with ITP and healthy controls,
despite the fact that the serum levels of interleukin (IL)-12p70, IL-8, IL-4,
interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in patients with ITP
were higher than those in the healthy controls. The platelet count was negatively
correlated with the frequency of circulating NKT cells in chronic ITP. These
results indicate that NKT cells may be involved in ITP with severe
thrombocytopenia, and NKT and Tregs may be important in cytokine deregulation in
chronic ITP.
PMID- 24348782
TI - Correlation between the single nucleotide polymorphisms of the human
phosphodiesterase 4D gene and the risk of cerebral infarction in the Uygur and
Han ethnic groups of Xinjiang, China.
AB - In this study, the correlation between the single nucleotide polymorphisms (SNPs)
at rs2910829 and rs918592 in the phosphodiesterase 4D (PDE4D) gene and cerebral
infarction in the Uygur and Han ethnic groups of Xinjiang, China were examined.
The study population consisted of 373 Uygur and Han patients with cerebral
infarction and 377 Uygur and Han control participants with no nervous system
diseases. Polymerase chain reaction-restriction fragment length polymorphism (PCR
RFLP) and gene sequencing methods were used to assess the SNPs at the rs2910829
and rs918592 loci in the PDE4D gene. The differences in genotype and allele
frequency distribution were compared between the two groups. The C allele
frequency of the rs2910829 locus in the PDE4D gene of the cerebral infarction
group (81.0%) was significantly higher than that of the control group (76.4%)
(P<0.05). Furthermore, the A allele frequency of the rs918592 locus in the PDE4D
gene in the Uygur cerebral infarction group was significantly higher than that of
the Uygur control group (P<0.05). There were no significant differences in the
genotype and allele frequency distributions between the Uygur and Han groups
(P>0.05). The A allele of the rs918592 locus may be associated with the
occurrence of cerebral infarction in the Uygur population. In addition, it was
indicated that the C allele of the rs2910829 locus in the PDE4D gene confers
susceptibility to cerebral infarction; however, no significant difference was
identified between Uygur and Han patients with cerebral infarction.
PMID- 24348783
TI - deltaEF1 upregulates CDK4 transcription via the E2-box element on the CDK4
promoter.
AB - The zinc finger-homeodomain transcription factor, delta-crystallin enhancer
factor 1 (deltaEF1) has been identified as a regulatory factor involved in the
promotion of breast cancer cell proliferation via the downregulation of p21 and
the upregulation of cyclin-dependent kinase-2 (CDK2) and CDK4 expression.
However, the molecular mechanisms underlying the regulation of CDK4 expression by
deltaEF1 have not yet been elucidated. The present study demonstrated that the
ectopic expression of deltaEF1 in MDA-MB-231 breast cancer cells significantly
increased the activity of the CDK4 promoter. Deletion of the E2-box (CACGTG),
which is located at position -197/-191 on the human CDK4 promoter, significantly
attenuated the activation of CDK4 transcription by deltaEF1. In addition, a CDK4
promoter-M construct was generated via site-directed mutagenesis of the E2-box on
the human CDK4 promoter. Luciferase assay showed that the activation of CDK4
promoter-M activity by deltaEF1 was markedly decreased compared with the CDK4
promoter-0.4k promoter. Knockdown of deltaEF1 using RNA interference resulted in
the inhibition of CDK4 promoter activity. These observations suggest that
deltaEF1 upregulates CDK4 transcription via the E2-box element on the CDK4
promoter.
PMID- 24348784
TI - Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated
from Pana quinquefolium, on permanent focal cerebral ischemic injury in rats.
AB - Oxidative stress is significant in the pathogenesis of cerebral ischemia. Panax
quinquefolium 20(S)-protopanaxadiol saponins (PQDS) have been demonstrated to
exhibit a variety of biological effects in the cardiovascular system as a result
of their antioxidant properties. However, little is known regarding the effect of
PQDS on cerebral ischemia. The purpose of this study was to investigate whether
PQDS exhibited protective effects against cerebral ischemia. A model of cerebral
ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague-Dawley
rats. Adult male rats were randomly divided into five groups: Sham, MCAO and PQDS
treatment groups at doses of 12.5, 25.0 and 50.0 mg/kg. The effects of PQDS on
neurological deficits, cerebral infarct area, brain water content, and the
malondialdehyde (MDA) and Ca2+ levels and Na+-K+-ATPase and superoxide dismutase
(SOD) activities in the brain tissue were analyzed, and the nitric oxide (NO)
content and nitric oxide synthase (NOS) activity in the serum were evaluated.
Moreover, the expression of Bcl-2 was analyzed using western blotting.
Pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly reduced the
neurological deficit score, decreased the infarcted area and decreased the brain
water content from 83.09 to 80.27% (P<0.05). In addition, PQDS pretreatment
decreased the NOS activity and the NO levels in the serum compared with those in
the MCAO group. Furthermore, pretreatment with PQDS (25.0 and 50.0 mg/kg)
significantly increased the activities of SOD and Na+-K+-ATPase and decreased the
levels of Ca2+ and MDA in the brain tissue (P<0.05) compared with those in the
MCAO group. Pretreatment with PQDS (25.0 and 50.0 mg/kg) also increased the
protein expression level of Bcl-2 compared with that in the MCAO group. The
histopathological results demonstrated the protective effect of PQDS on ischemic
injury. The results indicated that PQDS has protective effects against ischemic
injury in rats. The mechanism may be associated with the inhibition of oxidative
stress and apoptosis.
PMID- 24348785
TI - Correlation between superoxide dismutase 1 and 2 polymorphisms and susceptibility
to oral squamous cell carcinoma.
AB - Oxidative stress is significant in numerous types of cancer. Tobacco smoke, an
important risk factor for oral squamous cell carcinoma (OSCC), is able to
generate reactive oxygen species (ROS) and cause oxidative DNA damage. Superoxide
dismutase (SOD) is an endogenous antioxidant enzyme that is critical in limiting
the oxidative burden effectively. The purpose of this study was to investigate
the effects of the mitochondrial SOD2 and Cu/Zn enzyme SOD1 gene polymorphisms on
the susceptibility to and clinicopathological characteristics of OSCC, as well as
the synergistic effect between these gene polymorphisms and the well-known risk
factor of tobacco consumption. Patients with clinically diagnosed OSCC (n=362)
and healthy normal individuals (n=358) were investigated for four single
nucleotide polymorphisms (SNPs; rs4880, rs5746136, rs1804450 and rs11556620) by
polymerase chain reaction-restriction fragment length polymorphism and DNA
sequencing methods. Following adjustment for other confounders, no significant
difference was observed in the rs5746136 SOD2 SNPs between the patients and
controls. However, the incidence of the CT genotype of SOD2 SNP rs4880 was higher
in the patients than in normal subjects in the additive model [CT vs. TT;
P=0.045; adjusted odds ratio (AOR)=1.484; 95% confidence interval (CI), 1.009
2.182] and in the dominant model (CT/CC vs. TT; P=0.022; AOR=1.559; 95% CI, 1.067
2.278). For those who smoked, the incidence of the CT genotype of rs4880
increased markedly in the patients compared with the controls in the additive
model (CT vs. TT; P=0.003; AOR=2.325; 95% CI, 1.330-4.064) and in the dominant
model (CT/CC vs. TT; P=0.001; AOR=2.448; 95% CI, 1.417-4.230). For SOD1,
polymorphisms at rs1804450 and rs11556620 were not present in any of the OSCC or
control subjects. The results suggest that SOD2 rs4880 may be involved in the
tumorigenesis of OSCC and may be useful as a genetic susceptibility marker for
OSCC.
PMID- 24348786
TI - Forsythiaside attenuates lipopolysaccharide-induced inflammatory responses in the
bursa of Fabricius of chickens by downregulating the NF-kappaB signaling pathway.
AB - Forsythiaside, a phenylethanoside product isolated from air-dried fruits of
Forsythia suspensa, has been demonstrated to exhibit antioxidant, antibacterial
and anti-inflammatory activities in vitro. However, its mechanism and the effects
of lipopolysaccharide (LPS)-induced injury on the bursa of Fabricius (BF) of
chickens are poorly understood. The present study aimed to investigate the anti
inflammatory effects of forsythiaside on LPS-induced acute inflammation. In
addition, the potential molecular mechanisms of forsythiaside were analyzed in
the BF, a special immune organ in chickens. Forty 15-day-old chickens were
randomly divided into control, LPS and LPS plus forsythiaside (30 or 60 mg/kg)
groups (n=10 for each group). In the LPS plus forsythiaside (30 or 60 mg/kg)
groups, the chickens were orally administered with forsythiaside at doses of 30
and 60 mg/kg for seven days. At 21 days old, the chickens were intravenously
injected with 200 MUg/kg body weight LPS. Chickens in the control and LPS groups
were only administered with vehicle or LPS, respectively, at day 21. At 3 h post
injection, the body temperature and nitric oxide (NO) levels were analyzed. In
addition, the levels and mRNA expression of pro-inflammatory cytokines, including
tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1beta, and
the mRNA expression of nuclear factor-kappaB (NF-kappaB), cyclooxygenase-2 (COX
2) and inducible NO synthase (iNOS), were examined in the BFs isolated from the
chickens. The results revealed that forsythiaside was able to attenuate the LPS
induced inflammatory responses in the BFs of the chickens. The mechanisms by
which forsythiaside exerted its anti-inflammatory effect were found to correlate
with the inhibition of IL-6, IL-1beta, TNF-alpha and COX-2 production, via the
inactivation of NF-kappaB, indicating that the NF-kappaB-iNOS-NO signaling
pathway may be important in this process.
PMID- 24348787
TI - Clinicopathological features and prognosis of pseudomyxoma peritonei.
AB - The aim of this study was to evaluate the effects of treatment and the factors
influencing the postoperative recurrence and survival time for pseudomyxoma
peritonei (PMP). A total of 39 patients with PMP who received treatment were
analyzed in The General Hospital of PLA (Beijing, China) between 2002 and 2011.
The patients received cytoreductive surgery (CRS) and 25 cases of PMP recurred.
Seven patients received postoperative hyperthermic intraperitoneal chemoperfusion
(HIPEC). The median follow-up was 40 months. There were eight mortalities in this
period. The 5- and 10-year survival rates were 89.0 and 35.0%, respectively. The
medians of overall survival (OS) and recurrence time were 37 and 4 months,
respectively. Multivariate analyses revealed that pathological subtype was able
to influence the recurrence (P=0.042) and OS (P=0.033) times, as an independent
prognostic factor. HIPEC was significantly associated with postoperative
recurrence time (P=0.017). Patients with disseminated peritoneal adenomucinosis
had a more favorable prognosis. CRS combined with HIPEC was able to extend the
postoperative recurrence time for patients with PMP.
PMID- 24348788
TI - Apoptosis and p53 expression in the placental villi of females with unexplained
recurrent spontaneous abortion.
AB - The aim of this study was to explore the level of apoptosis and p53 expression in
the placental villi of patients with unexplained recurrent spontaneous abortion
(URSA). Fifty-three pregnant females with URSA and 32 pregnant females who
required an induced abortion were selected as the subjects of this study.
Placental villus tissues were collected from June 2010 to June 2012 and
quantitative polymerase chain reaction (qPCR) and immunohistochemical analysis
were performed to determine the mRNA and protein levels of p53 in the placental
villus tissues. The level of apoptosis in the tissues was studied using terminal
deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. The
mRNA and protein expression levels of p53 in the URSA group were significantly
higher than those in the control group (P<0.05). Furthermore, the levels of
apoptosis were increased markedly in the URSA group compared with the control
group (P<0.05). In conclusion, the placental villi of patients with URSA express
a high level of p53, which may result in cell apoptosis and lead to recurrent
spontaneous abortion.
PMID- 24348789
TI - Role of nuclear factor of activated T cells 1 in the pathogenesis of
osteoarthritis.
AB - Osteoarthritis (OA) is the most common form of joint disease in middle-aged
individuals and the elderly. Previous studies have shown that the overexpression
of matrix-degrading proteinases and proinflammatory cytokines is associated with
the degradation of osteoarthritic cartilage. However, the transcription factors
involved remain unclear. The present study aimed to determine the expression
levels of nuclear factor of activated T cells 1 (NFAT1), interleukin-1beta (IL
1beta) and tumor necrosis factor-alpha (TNF-alpha) in patients with OA, and to
validate the role of NFAT1 in the pathogenesis of OA. The expression levels of
NFAT1, IL-1beta and TNF-alpha in chondrocytes in the cartilage of patients with
OA and healthy individuals were evaluated using western blot analysis. A
luciferase reporter assay was performed to determine the activity of NFAT1 in
primary human chondrocytes that were transfected with pNFAT1-luc plasmid and
stimulated by IL-1beta. An enzyme-linked immunosorbent assay was performed to
detect the levels of TNF-alpha, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9
in the supernatant of cultured chondrocytes in which the NFAT1 was silenced. The
expression levels of NFAT1, IL-1beta and TNF-alpha in the cartilage of patients
with OA were higher than those of the controls. IL-1beta induced the expression
of NFAT1 in primary chondrocytes. The expression levels of TNF-alpha, MMP-1, -3
and -9 promoted by IL-1beta were decreased in NFAT1-silenced chondrocytes. In
conclusion, NFAT1 may be important in the pathogenesis of OA and calcineurin-NFAT
inhibitors may be potential effective agents for the treatment of OA.
PMID- 24348790
TI - MDCT and MRI for the diagnosis of complex fractures of the tibial plateau: A case
control study.
AB - The aim of this study was to evaluate the clinical value of multidetector-row
computed tomography (MDCT) and magnetic resonance imaging (MRI) in the diagnosis
and treatment of complex fractures of the tibial plateau. A total of 71 patients
with complex fractures of the tibial plateau (estimated Schatzker classifications
III, V and VI) were included in this study. The X-ray, MDCT and MRI data obtained
from the patients were analyzed. MDCT was the most sensitive method in the
diagnosis of tibial articular surface collapse, cruciate ligament tibial avulsion
fracture, degree of fracture comminution and degree of fracture displacement
(P<0.01). MRI was the most sensitive method in the diagnosis of injuries of the
cruciate and collateral ligaments, menisci and cartilage peeling of the articular
surfaces (P<0.01). MDCT and MRI were demonstrated to be more sensitive than X
rays for the diagnosis of insidious damage around the knee.
PMID- 24348791
TI - Construction and identification of the recombinant plasmid pET30a-EgA31-Eg95 of
Echinococcus granulosus.
AB - To clone the Eg95 and EgA31 antigen genes into the prokaryotic expression plasmid
pET30a-EgA31-Eg95, we expressed the recombinant protein EgA31-Eg95 and confirmed
with western blot analysis. The total RNA was extracted from the protoscoleces of
Echinococcus granulosus (E. granulosus) adult worms. The complementary DNA (cDNA)
encoding the EgA31 antigen was amplified via quantitative real-time polymerase
chain reaction (qPCR). The recombinant plasmid pET30a-EgA31 was used as a carrier
and was connected with the Eg95 vector. The recombinant plasmid pET30a-EgA31-Eg95
was constructed and the fusion protein EgA31-Eg95 was detected using sodium
dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The positive clone
was the empty recombinant vector. The recombinant protein pET30a-EgA31-Eg95 was
~46 kDa, and the expressed product accounted for approximately 20% of the total
soluble proteins. We successfully constructed the recombinant plasmid pET30a
EgA31-Eg95 and expressed the recombinant protein EgA31-Eg95. The results may be
the foundation of research on its immunogenicity in the future.
PMID- 24348792
TI - UPLC-PDA determination of paeoniflorin in rat plasma following the oral
administration of Radix Paeoniae Alba and its effects on rats with collagen
induced arthritis.
AB - Rheumatoid arthritis (RA) is a chronic disabling autoimmune disease with
characteristics of chronic, progressive inflammatory joint synovial damage, which
mainly encroaches upon the synovium of the joint. The use of traditional medicine
to treat RA slows the development of RA to a certain extent; however, it often
has numerous side-effects. Therefore, the focus of RA research is the
identification of a new, safe and effective medicine. The aim of the present
study was to use an ultra performance liquid chromatography and photo diode array
(UPLC-PDA) method to detect the paeoniflorin component in a Radix Paeoniae Alba
decoction and in rat plasma following the oral administration of Radix Paeoniae
Alba decoction. In addition, the effects of paeoniflorin on collagen-induced
arthritis (CIA) in rats were investigated. The results indicate that a UPLC-PDA
method for determining the presence of paeoniflorin in the Radix Paeoniae Alba
decoction was successfully established. The method was fast, simple, sensitive,
precise and valid. Paeoniflorin was shown to be a bioactive component of the
Radix Paeoniae Alba decoction that was absorbed into rat plasma. Paeoniflorin
significantly improved the disease resistant ability of RA rats and reduced the
levels of the inflammatory cytokines, IL-1beta and TNF-alpha, thereby inhibiting
inflammation and bone erosion in the rats with CIA. The observations are likely
to lay the foundation for further study of the mechanism of paeoniflorin in the
treatment of RA.
PMID- 24348793
TI - Combination of hearing screening and genetic screening for deafness
susceptibility genes in newborns.
AB - The aim of this study was to determine the clinical significance of the results
of screening of newborn hearing and the incidence of deafness-susceptibility
genes. One thousand newborn babies in the Handan Center Hospital (Handan, China)
underwent screening of hearing and deafness-susceptibility genes. The first
screening test was carried out using otoacoustic emissions (OAEs). Babies with
hearing loss who failed to pass the initial screening were scheduled for
rescreening at 42 days after birth. Cord blood was used for the screening of
deafness-susceptibility genes, namely the GJB2, SLC26A4 and mitochondrial 12S
rRNA (MTRNR1) genes. Among the 1,000 neonates that underwent the first hearing
screening, 25 exhibited left-sided hearing loss, 21 exhibited right-sided hearing
loss and 15 cases had binaural hearing loss. After rescreening 42 days later,
only one of the initial 61 cases exhibited hearing loss under OAE testing. The
neonatal deafness gene tests showed two cases with 1555A>G mutation and two cases
with 1494C>T mutation of the MTRNR1 gene. In the SLC26A4 gene screening, four
cases exhibited the heterozygous IVS7-2A>G mutation and one case exhibited
heterozygous 1226G>A mutation. In the GJB2 gene screening, two cases exhibited
the homozygous 427C>T mutation and 10 exhibited the heterozygous 235delC
mutation. The genetic screening revealed 21 newborns with mutations in the three
deafness-susceptibility genes. The overall carrier rate was 2.1% (21/1,000). The
association of hearing and gene screening may be the promising screening strategy
for the diagnosis of hearing loss.
PMID- 24348794
TI - Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala
kindled epileptic rats.
AB - The objective of this study was to analyze the changes in expression and the
possible functions of interleukin-6 (IL-6) in electrical kindling of the
basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted
into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic
electrical stimulation through the electrodes to induce kindling. The seizure
characteristics and behavioral changes of the rats were observed, and
electroencephalograms were recorded during and following kindling. The IL-6 mRNA
expression in the hippocampi of the rats was analyzed using semi-quantitative
reverse transcription-polymerase chain reaction, and control and topiramate (TPM)
treated groups were compared. The mean time-period required for kindling was
13.50+/-3.99 days, and the afterdischarge duration (ADD) measured between 21,450
and 119,720 msec. The expression of IL-6 mRNA was significantly upregulated in
the kindled rats. TPM was able to depress the seizures and decrease the IL-6
level in the kindled rats. In conclusion, IL-6 mRNA was upregulated in the
hippocampi of epileptic rats, and IL-6 may have participated in the process of
kindling.
PMID- 24348795
TI - Fucoidan induces caspase-dependent apoptosis in MC3 human mucoepidermoid
carcinoma cells.
AB - Fucoidan is a sulfated polysaccharide present in brown algae that has been
identified to exhibit multiple biological effects. In this study, the apoptotic
effects of fucoidan in MC3 human mucoepidermoid carcinoma (MEC) cells were
investigated. The apoptotic effects of fucoidan on MC3 MEC cells were evaluated
by cell proliferation assay, 4',6-diamidino-2-phenylindole staining and western
blot analysis. The results showed that fucoidan decreased cell proliferation and
induced caspase-dependent apoptosis in MC3 MEC cells. Fucoidan downregulated the
phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, whereas
phospho-p38 mitogen-activated protein kinase or phospho-c-Jun NH2-terminal kinase
(JNK) levels were not altered. In addition, fucoidan significantly decreased the
expression levels of myeloid cell leukemia-1 (Mcl-1). These results suggest that
fucoidan is able to modulate the ERK1/2 pathway and thereby regulate Mcl-1
protein expression and induce apoptosis in MC3 MEC cells. Therefore, fucoidan may
be a promising agent for the treatment of human MEC.
PMID- 24348796
TI - Evaluation of acoustic radiation force impulse imaging for the
clinicopathological typing of renal fibrosis.
AB - This study aimed to explore the assessment value of virtual touch quantization
(VTQ) for the clinicopathological typing of renal fibrosis. The quantitative
detection of 76 patients with nephropathy was performed using acoustic radiation
force impulse imaging (ARFI). The extent of the renal fibrosis in each patient
was confirmed using ultrasound-guided biopsy pathology. The VTQ values were
compared with the degree of renal fibrosis in order to analyze the correlation
between them. Patients were divided pathologically into four groups, as follows:
non-fibrosis (n=14), mild fibrosis (n=40), moderate fibrosis (n=21) and severe
fibrosis (n=1). Compared with the non-fibrosis group, the VTQ values of the mild
and moderate fibrosis groups were significantly increased (P<0.01); however,
there was no significant difference between the VTQ values of the mild and
moderate fibrosis groups (P>0.05). According to the receiver operating
characteristic (ROC) curve, a VTQ value of renal parenchyma of >1.67 m/sec was
determined to be an indicator of renal fibrosis, with a sensitivity of 86.3% and
a specificity of 83.3%. VTQ technology may be significant in the assessment of
the extent of renal fibrosis.
PMID- 24348797
TI - Expression of toll-like receptor 4 in maternal monocytes of patients with
gestational diabetes mellitus.
AB - Toll-like receptors (TLRs) are pattern recognition receptors and play an
important role in innate immune responses and the occurrence of inflammatory
disease. TLR4 is a member of the TLR family and its activation is capable of
inducing inflammatory responses, reflecting a relationship between the innate and
adaptive immune systems. However, whether TLR4 is expressed in patients with
gestational diabetes mellitus (GDM) has not been elucidated. The aim of the
present study was to investigate whether TLR4 is expressed in maternal peripheral
blood monocytes of patients with GDM. A case-control study, using standard
quantitative polymerase chain reaction and western blotting, was performed to
assess the TLR4 expression in 30 females with GDM and 32 healthy pregnant females
at similar gestational ages. Serum tumor necrosis factor (TNF)-alpha levels were
assessed using ELISA in all the females. The TLR4 expression levels in the
maternal peripheral blood monocytes and the serum TNF-alpha levels were increased
in females with GDM compared with healthy pregnant females (P<0.05).
Additionally, there was a positive correlation between the TLR4 expression level
in peripheral blood monocytes and serum TNF-alpha levels in all the females.
These results indicate that TLR4-mediated release of inflammatory cytokines may
represent one factor leading to increased glucose levels in patients with GDM. In
addition, TLR4 may be involved in the pathogenesis of GDM.
PMID- 24348798
TI - Variations in NAG-1 expression of human gastric carcinoma and normal gastric
tissues.
AB - Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a member of the
transforming growth factor beta (TGF-beta) superfamily, has been demonstrated to
possess antitumorigenic and proapoptotic activities in gastric cancer cells. In
the present study, the expression of NAG-1 was assessed in human gastric
carcinoma, tumor-adjacent normal tissues and normal gastric mucosa, with the aim
to investigate the role of NAG-1 in the carcinogenesis and development of gastric
carcinoma. NAG-1 protein expression was evaluated using immunohistochemical
staining, while the expression of NAG-1 mRNA was evaluated using reverse
transcription-polymerase chain reaction. It was observed that adenocarcinoma
tissues had a lower expression of NAG-1 than normal gastric tissues. Furthermore,
moderately and well-differentiated adenocarcinoma tissues expressed more NAG-1
protein than the poorly differentiated adenocarcinoma tissues. The expression of
NAG-1 protein in adenocarcinoma tissues did not correlate with tumor-node
metastasis staging, infiltration degree or tumor size. The NAG-1 mRNA expression
in adenocarcinoma tissues was also lower than that in normal gastric tissues. In
conclusion, NAG-1 was poorly expressed in adenocarcinoma tissues and inversely
correlated with the degree of tumor differentiation. These results indicate that
NAG-1 may have an anti-oncogenic function in the carcinogenesis and development
of gastric carcinoma, and that its attenuated or absent expression may lead to
gastric carcinogenesis.
PMID- 24348799
TI - In vitro studies on the cytotoxicity, and elastase and tyrosinase inhibitory
activities of marigold (Tagetes erecta L.) flower extracts.
AB - Marigold (Tagetes erecta L.) has long been used as a medicinal herb for a number
of therapeutic activities. In the present study, the cytotoxicities of ethanol
and ethyl acetate extracts of marigold flowers and their inhibitory effects on
elastase and tyrosinase enzymes were investigated. An MTT assay was performed to
measure the cytotoxicity of these two extracts on the H460 lung cancer and the
Caco-2 colon cancer cell lines. An elastase assay kit, based on the digestion of
a non-fluorescent elastin substrate to highly fluorescent fragments by elastase,
was used for the elastase inhibition assay. Tyrosinase inhibition activity was
investigated using the dopachrome method with L-3,4-dihydroxyphenylalanine (L
DOPA) as a substrate. The data obtained in this study demonstrated that the
extracts were nontoxic to H460 and Caco-2 cell lines. The elastase inhibition
activities of ethanol (250 MUg/ml) and ethyl acetate (125 MUg/ml) extracts were
found to be significantly higher than that of the negative control. The
tyrosinase inhibition activities of ethanol and ethyl acetate extracts, in terms
of the mean inhibition concentration (IC50), were 1,078 and 1,467 MUg/ml,
respectively. To the best of our knowledge, the present study has demonstrated
for the first time that marigold flower extracts possess tyrosinase inhibition
activity. The activities of ethanol and ethyl acetate extracts of marigold
flowers were investigated in vitro and indicated that these extracts possess
useful properties that may be of interest for cosmetic development.
PMID- 24348800
TI - Terson syndrome with no cerebral hemorrhage: A case report.
AB - The present study reports the case of a 33-year-old male who presented with
Terson syndrome with no cerebral hemorrhage secondary to traumatic brain injury
(TBI). A computed tomography scan of the patient, who had sustained an impact
injury to the right occipital region, showed no cerebral lesion. Ophthalmoscopy
clearly demonstrated vitreous hemorrhage in both eye globes. Vitreous hemorrhage,
which results from an abrupt increase in intracranial pressure (ICP), is
associated with TBI. In this case, the visual disturbance was attributed to
Terson syndrome secondary to TBI. Therefore, close ophthalmological and
radiological evaluation is required in patients with TBI, in order to enable the
diagnosis of Terson syndrome and an early vitrectomy.
PMID- 24348801
TI - Baicalin protects the myocardium from reperfusion-induced damage in isolated rat
hearts via the antioxidant and paracrine effect.
AB - The aim of the present study was to investigate the protective effect of baicalin
(BA) against ischemia-reperfusion (I/R) injury in isolated rat hearts. Sprague
Dawley rat hearts were rapidly removed, mounted on a Langendorff apparatus and
subjected to 30 min ischemia followed by 30 min reperfusion with Krebs-Henseleit
(K-H) solution at 37 degrees C to establish the isolated I/R injury model. All
animals (n=50) were randomly divided into five groups (n=10 in each): I, normal
control; II, I/R; III, I/R plus 20 mg/kg BA; IV, I/R plus 40 mg/kg BA; and V, I/R
plus 80 mg/kg BA. The degree of heart injury caused by the I/R was assessed by
evaluating left ventricular function and by detecting the levels of lactate
dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the
myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the
isolated rat hearts. Myocardial infarct size and vascular density were assessed
using histology and immunohistochemistry. The apoptotic cardiomyocytes were
determined using flow cytometry (FCM). Compared with group II, the BA groups
demonstrated improved left ventricular function, reduced CK and LDH release in
the coronary effluent and increased SOD and MDA activity (P<0.05). Furthermore,
histology and immunohistochemistry results showed that the infarct size was
reduced and vessel density was augmented in the BA groups (P<0.01) compared with
group II. The FCM results indicated that apoptosis was significantly lower in the
BA groups than in group II (P<0.05) and that the protective effect was dose
dependent. In conclusion, these results demonstrated that BA exerts a dose
dependent protective effect on I/R injury in isolated rat hearts, the mechanisms
of which may be associated with antioxidant and anti-apoptosis properties. To the
best of our knowledge, this study is the first evaluation of the efficacy of BA
in isolated rat hearts using histology and immunohistochemistry, providing a
foundation for the use of BA in the treatment of acute myocardial infarction.
PMID- 24348803
TI - Surgical treatment of a ventricular aneurysm in a patient with essential
thrombocythemia complicated by acute myocardial infarction: A case report.
AB - Essential thrombocythemia (ET) is a chronic clonal myeloproliferative disorder,
which is often complicated by arterial or venous thrombosis and idiopathic
bleeding diathesis. The present study reports a female patient with ET
complicated by acute myocardial infarction, leading to ventricular aneurysm
following interventional therapy for 3 years and a subsequent in-stent
restenosis. Following careful examination, a ventricular aneurysm resection and
coronary artery bypass graft were carried out. During this case, the monitoring
and controlling of the platelet count, pre- and post-operatively, was extremely
important for successful surgery.
PMID- 24348804
TI - Correlation analysis between the rate of respiration in the root and the active
components in licorice (Glycyrrhiza uralensis).
AB - The aim of this study was to investigate the correlation between root respiration
and the percentage of active components in licorice (Glycyrrhiza uralensis
Fisch.), in order to provide a foundation for the regulation and modulation of
the quality of G. uralensis. Respiration efflux of annual and biennial G.
uralensis was determined using a Li-7000 CO2/H2O analyzer. The root systems were
scanned at a resolution of 3,000 dpi using an Epson Expression 10000XL scanner.
Root growth was determined by analyzing the scanned images using WinRHIZO version
Pro2007d software and the rate of respiration in the root was subsequently
calculated. In addition, the percentages of the five major active components in
licorice, glycyrrhizic acid, glycyrrhizin, isoliquiritin, liquiritigenin and
isoliquiritigenin, were detected using high-performance liquid chromatography
(HPLC). The correlation between the root respiration and the percentage of the
active components was investigated. Significant seasonal changes were observed in
the rates of respiration of first and zero-class roots. In annual and biennial G.
uralensis, the maximum and minimum values for rate of respiration were present in
July (P<0.05) and November (P<0.05), respectively. The correlation coefficients
between the five major active components and the rate of respiration were -0.304
(glycyrrhizin), -0.129 (liquiritigenin), -0.441 (glycyrrhizic acid; P<0.05),
0.471 (isoliquiritin; P<0.05) and 0.148 (isoliquiritigenin). The percentages of
glycyrrhizic acid and isoliquiritin were significantly negatively correlated with
the rate of respiration in annual and biennial G. uralensis. Understanding the
correlation between the root rate of respiration and the active components in G.
uralensis may be beneficial to ensuring the quality of cultivated G. uralensis.
PMID- 24348802
TI - Grape seed extract attenuates arsenic-induced nephrotoxicity in rats.
AB - Oxidative stress is a recognized factor in nephrotoxicity induced by chronic
exposure to inorganic arsenic (As). Grape seed extract (GSE) possesses
antioxidant properties. The present study was designed to evaluate the beneficial
effects of GSE against arsenic-induced renal injury. Healthy, male Sprague-Dawley
rats were exposed to As in drinking water (30 ppm) with or without GSE (100
mg/kg) for 12 months. The serum proinflammatory cytokine levels and mRNA
expression levels of fibrogenic markers in the renal tissues were evaluated using
enzyme-linked immunosorbent assay and quantitative polymerase chain reaction,
respectively. The protein expression levels of nicotinamide adenine dinucleotide
phosphate (NADPH) subunits, transforming growth factor-beta1 (TGF-beta1) and
phosphorylated Smad2/3 (pSmad2/3) were assessed using western blot analysis. The
results demonstrated that cotreatment with GSE significantly improved renal
function, as demonstrated by the reductions in relative kidney weight (% of body
weight) and blood urea nitrogen, and the increase in the creatinine clearance
capacity. GSE attenuated the As-induced changes in the serum levels of tumor
necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1beta and the mRNA
levels of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), connective tissue
growth factor (CTGF) and fibronectin (FN) in renal tissue. Furthermore,
administration of GSE markedly reduced As-stimulated reactive oxygen species
(ROS) production and Nox activity, as well as the protein expression levels of
the NADPH subunits (Nox2, p47phox and Nox4). In addition, GSE cotreatment was
correlated with a significant reduction in TGF-beta/Smad signaling, as
demonstrated by the decreased protein levels of TGF-beta1 and pSmad2/3 in renal
tissue. This study indicated that GSE may be a useful agent for the prevention of
nephrotoxicity induced by chronic exposure to As. GSE may exert its effects
through the suppression of Nox and inhibition of TGF-beta/Smad signaling
activation.
PMID- 24348805
TI - Potential beneficial effects of oral administration of isoflavones in patients
with chronic mountain sickness.
AB - Soy isoflavones (Ifs), which are natural phytoestrogens, have beneficial effects
in cardiovascular disease. We have previously shown that genistein, the most
active component of Ifs, inhibits pulmonary vascular structural remodeling and
right ventricular hypertrophy induced by chronic hypoxia in male Wistar rats.
This study aimed to evaluate the effects of Ifs on right ventricular and
pulmonary hemodynamics in individuals with chronic mountain sickness (CMS).
Twenty-eight male patients living on the Qinghai-Tibetan plateau (5,200 m) who
were suffering from CMS were treated orally with Ifs (20 mg, twice daily) for 45
days. Physiological and plasma biochemical indices, hematology and
echocardiography were investigated. It was observed that 45 days of treatment
with Ifs significantly increased blood oxygen saturation and markedly decreased
the CMS score and heart rate (all P<0.05) of the subjects. Following treatment
with Ifs, hematocrit (P<0.05), hemoglobin concentration (P<0.01) and plasma
levels of malondialdehyde (P<0.05) were significantly decreased, while plasma
levels of nitric oxide (P<0.01) and the plasma activity of nitric oxide synthase
(P<0.01) and superoxide dismutase (P<0.01) were markedly increased compared with
the respective values obtained prior to treatment with Ifs. The echocardiography
results showed that Ifs significantly decreased the main pulmonary artery
diameter (P<0.05), right ventricular end-diastolic anteroposterior diameter
(P<0.01), right ventricular end-diastolic trans diameter (P<0.01), right
ventricular anterior wall (P<0.01) and right ventricular outflow tract (P<0.01).
These results indicate the potential beneficial effects of Ifs in the reduction
of excessive erythrocytosis, the alleviation of oxidative damage and the
amelioration of right ventricular index and pulmonary hemodynamics in CMS.
PMID- 24348806
TI - Correlation between matrix metalloproteinase expression and activation of the
focal adhesion kinase signaling pathway in herpes stromal keratitis.
AB - The present study aimed to investigate the correlation between matrix
metalloproteinase-2 (MMP-2) expression and activation of the focal adhesion
kinase (FAK) signaling pathway in herpes stromal keratitis (HSK). The cornea of
24 BALB/c mice was infected with herpes simplex virus type 1 (HSV-1) to construct
a model of HSK. Six additional mice served as negative controls.
Immunohistochemical staining was used to detect FAK expression levels. Human
corneal epithelial (HCE) cells cultured in vitro were infected with HSV-1 and the
expression levels of MMP-2, FAK and phosphorylated-FAK (p-FAK) in HCE cells were
detected using reverse transcription-polymerase chain reaction (RT-PCR), western
blot analysis and immunohistochemistry at 2, 20 and 40 h following infection. In
the HSK rat model, the corneal epithelial cells appeared deranged and the number
of neutrophils and FAK-positive cells was significantly increased compared with
that of the negative control group (P<0.05). Repeated measures analysis of
variance of RT-PCR showed no significant differences in MMP-2 and FAK mRNA
expression levels in the infected cells at various time points, and no
significant differences between infected cells and the negative control group
were observed. There was no interaction between groups and time points. Pairwise
comparisons showed that MMP-2 and FAK mRNA expression levels were significantly
increased in virus-infected cells compared with those of the control group. Over
time, MMP-2 and FAK mRNA expression levels did not differ significantly in virus
infected cells or in control cells. Western blot analysis indicated no
significant differences in p-FAK, FAK and MMP-2 expression levels between the
infected and control cells at 2 h (P>0.05). Infected cells showed a significant
increase in MMP-2 and p-FAK expression levels than that of the control cells at
20 and 40 h (P<0.05). p-FAK, FAK and MMP-2 expression levels in virus-infected
cells at 2 h differed significantly from those at 20 and 40 h (P<0.05).
Immunohistochemical staining results showed that a longer infection time was
associated with an increased number of cells staining positive for MMP-2, FAK and
p-FAK. Following HSV-1 infection of the corneal epithelium, the FAK signaling
pathway was activated, resulting in increased secretion of MMP-2 in the corneal
tissue and accelerated formation of corneal ulcers and necrotic lesions.
PMID- 24348807
TI - Giant epidermal cyst in the posterior neck developing over 40 years: A case
report.
AB - Conventional epidermal cysts are generally small, slow-growing, non-tender, dome
shaped lesions. An epidermal cyst is usually asymptomatic until it is infected or
enlarged to the extent that it causes damage to adjacent anatomical structures.
However, few cases of giant epidermal cysts in the neck have been reported. The
present case reports a giant epidermal cyst in the posterior neck, which grew to
an extremely large size for >40 years without inflammation or rupture, and was
misdiagnosed as a large soft tissue neoplasm. The patient exhibited depression
and developed social anxiety due to the negative cosmetic consequences of the
large mass. The patient underwent excision of the mass. At the follow-up
examination two years postoperatively, there were no local recurrence and the
psychiatric symptoms of the patient were completely resolved. To the best of our
knowledge, a giant epidermal cyst growing for >40 years has not previously been
reported.
PMID- 24348808
TI - Effect of 15-hydroxyprostaglandin dehydrogenase gene on the proliferation of
gastric cancer cell murine forestomach carcinoma.
AB - The aim of the present study was to construct the eukaryotic expression vector
pcDNA3.1/15-PGDH. The vector was used to transfect mouse murine forestomach
carcinoma (MFC) cancer cells and observe the effects of 15-hydroxyprostaglandin
dehydrogenase (15-PGDH) on the proliferation of MFC. pcDNA3.1/15-PGDH was
constructed using gene recombination technology and the vector was used to
transfect MFC cells to build a stable transfected cell strain. The expression
levels of 15-PGDH in the transfected cells were detected using reverse
transcription polymerase chain reaction. Optical Density (OD) values were
determined using an MTT assay and used to draw cell growth curves. The effects of
15-PGDH on the proliferation of MFC were observed using a clone formation
experiment. Following successful transfection by 15-PGDH, the relative expression
levels of 15-PGDH in the MFC/15-PGDH cells were significantly higher (1.06+/
0.08) (P<0.01) compared with the empty plasmid-transfected group (0.22+/-0.01)
and the untransfected group (0.21+/-0.01). Following transfection by 15-PGDH,
cell growth was markedly inhibited. The MTT results showed that on days 4, 6 and
8, the 15-PGDH-transfected group had a low OD on average, which was significantly
different (P<0.05) from the empty plasmid-transfected group or the untransfected
group. The 15-PGDH-transfected group had a plating efficiency of 18%, and
compared with the untransfected group (63%) and the empty plasmid-transfected
group (59%), clone formation was significantly inhibited (P<0.01). Results of the
present study indicate that transfection by 15-PGDH may significantly inhibit the
proliferation and clone formation of MFC cells.
PMID- 24348809
TI - Insulin augments mechanical strain-induced ERK activation and cyclooxygenase-2
expression in MG63 cells through integrins.
AB - Insulin has been proposed to be a positive regulator of osteoblast proliferation
and bone formation. In vivo mechanical loading is essential for maintaining
skeletal integrity and bone mass. Since insulin and mechanical force activate
similar signaling pathways in osteoblasts, it was hypothesized that insulin may
affect mechanical stimulation in osteoblasts. The present study tested the
hypothesis that insulin augments mechanical strain-induced signaling and early
gene expression in MG63 cells via activation of the extracellular signal
regulated kinase (ERK) pathway and cyclooxygenase-2 (Cox-2) expression. Western
blot analysis and quantitative polymerase chain reaction demonstrated
respectively that insulin enhanced mechanical strain-induced ERK phosphorylation
and Cox-2 expression levels in a dose-dependent manner. The effect of insulin on
mechanical strain-induced Cox-2 expression was inhibited by blockade of the ERK
pathway. In addition, echistatin, an inhibitor of integrin function, prevented
the effects of insulin on mechanical strain-induced ERK phosphorylation and Cox-2
expression. The data obtained from this study suggested that insulin augments
mechanical strain-induced Cox-2 expression levels via integrin-dependent
activation of the ERK pathway in osteoblasts.
PMID- 24348810
TI - Serum from patients with hepatitis E virus-related acute liver failure induces
human liver cell apoptosis.
AB - The pathogenesis of acute liver failure has not been fully elucidated. The
present study investigated the effects of the serum from patients with hepatitis
E virus (HEV)-related acute liver failure on human liver cell survival and
apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS)
antibody recognizing core polysaccharide against acute liver failure serum
induced apoptosis. Serum was collected from patients with HEV-related acute liver
failure. The levels of endotoxin (LPS) in the serum were measured using a
quantitative tachypleus amebocyte lysate endotoxin detection kit with a
chromogenic endpoint. Serum with a mean concentration of LPS was incubated with
L02 human liver cells and the rate of apoptosis was detected by flow cytometry.
The apoptotic rate was also evaluated in liver cells incubated with antibody and
the HEV-related acute liver failure serum. The results indicated that the
concentration of LPS in the serum of patients with HEV-related acute liver
failure was 0.26+/-0.02 EU/ml, which was significantly higher than that of the
control group (P<0.05). The rate of apoptosis in the human liver cells induced by
acute liver failure serum was 5.83+/-0.42%, which was significantly increased
compared with that in the cells treated with the serum of healthy individuals
(P<0.05). The apoptotic rate of the cells incubated with antibody and the acute
liver failure serum was 5.53+/-0.51%, which was lower than that of the cells
incubated with acute liver failure serum alone (P>0.05). These results indicate
that the serum of patients with HEV-related acute liver failure induces the
apoptosis of human liver cells. LPS may be directly involved in the apoptosis of
human liver cells. Moreover, the presence of the antibody did not significantly
reduce the level of apoptosis of liver cells exposed to HEV-related acute liver
failure serum.
PMID- 24348812
TI - Prognostic factors associated with locally recurrent rectal cancer following
primary surgery (Review).
AB - Locally recurrent rectal cancer (LRRC) is defined as an intrapelvic recurrence
following a primary rectal cancer resection, with or without distal metastasis.
The treatment of LRRC remains a clinical challenge. LRRC has been regarded as an
incurable disease state leading to a poor quality of life and a limited survival
time. However, curative reoperations have proved beneficial for treating LRRC. A
complete resection of recurrent tumors (R0 resection) allows the treatment to be
curative rather than palliative, which is a milestone in medicine. In LRRC cases,
the difficulty of achieving an R0 resection is associated with the post-operative
prognosis and is affected by several clinical factors, including the staging of
the local recurrence (LR), accompanying symptoms, patterns of tumors and combined
therapy. The risk factors following primary surgery that lead to an increased
rate of LR are summarized in this study, including the surgical, pathological and
therapeutic factors.
PMID- 24348813
TI - Analysis of the anticancer activity of curcuminoids, thiotryptophan and 4
phenoxyphenol derivatives.
AB - Curcumin, a non-nutritive yellow pigment derived from the rhizome of Curcuma
longa (turmeric), is considered to be an established nutraceutical with
anticancer activity. Turmeric contains three principal components, curcumin,
demethoxycurcumin and bisdemethoxycurcumin, of which curcumin is most abundant
and potent. The concurrence of a high consumption of turmeric and a low incidence
of prostate cancer in Asian countries may suggest a role for curcumin in
chemoprevention. Curcumin has been identified to exhibit anti-inflammatory, anti
oxidative and anticarcinogenic properties. Since the compound does not exhibit
side effects, curcumin has been designated for several clinical trials as a
treatment for human cancers. The pro-apototic, antioxidant and anti-inflammatory
characteristics of curcumin are implicated in its anticancer activity, yet the
mechanism of action of curcumin remains unknown. To achieve an effective
pharmacological outcome, curcumin must reach and sustain appropriate levels at
the site of action. However, the main disadvantage of curcumin is its high
metabolic instability and poor aqueous solubility that limits its systemic
bioavailability. To overcome this difficulty, the present study tested the
anticancer activity of new curcumin-like compounds (E21cH and Q012095H). Also,
the use of new medicaments requires an understanding of their pharmacokinetic
profiles and targets. Thus, molecular modeling methods were used to identify the
targets of curcumin and curcumin-like compounds compared with other anticancer
drugs (Q012138 and Q012169AT), which were used as the controls. The present study
identified several enzymes that are targeted by curcumin, aldo-keto reductase
family 1 member B10 (AKR1B10), serine/threonine-protein kinase, protein kinase C,
matrix metalloproteinase (MMP), cyclooxygenase and epidermal growth factor
receptor, which were tested as targets for these anticancer chemicals. All the
examined small compounds demonstrated anticancer activity in the in vitro
experiments and may impact cancer cells by acting on AKR1B10, MMP-9 and their
targets.
PMID- 24348814
TI - Endoplasmic reticulum stress in diethylnitrosamine-induced rat liver cancer.
AB - To analyze the significance of endoplasmic reticulum stress (ERS) in the
development of diethylnitrosamine (DEN)-induced liver cancer in rats, critical
regulatory factors in ERS signaling pathways were investigated in the present
study. The results showed that the expression of ERS-related proteins gradually
increased in the early and mid-term stages of carcinogenesis, while in the later
stages, the expression of these proteins did not change significantly after
reaching a peak. ERS is involved in DEN-induced rat liver injury, the
proliferation of liver cells and the occurrence and development of liver
cirrhosis. However, ERS did not affect hepatoma cell growth following the
formation of rat liver cancer in the current study.
PMID- 24348811
TI - Lentiviral vector-based therapy in head and neck cancer (Review).
AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm
worldwide. Despite advances in multimodality treatments involving surgery,
radiation and chemotherapy, the five-year survival rate has remained at ~50% for
the past 35 years. Therefore, the early detection of recurrent or persistent
disease is extremely important. Replication-incompetent HIV-1-based lentiviral
vectors have emerged as powerful and safe tools for gene delivery. Commonly,
HNSCC is a locoregional disease that presents at or close to the body surface.
Thus, HNSCC is amendable to intratumoral injections of gene therapy vectors aimed
at correcting defects associated with tumor suppressor genes to induce the direct
cytotoxicity of cancer cells or immune modulation to promote antitumor immunity.
Current investigations analyzing HNSCC gene mutations and stem cell markers and
the cancer immunoediting concept are creating exciting therapeutic opportunities
for lentiviral and other gene transfer vectors. The present review reports
specific examples of the current applications of lentiviral vectors in HNSCC.
PMID- 24348815
TI - Inhibition of Annexin A2 gene transcription is a promising molecular target for
hepatoma cell proliferation and metastasis.
AB - Hepatocyte Annexin A2 (ANXA2) expression is associated with the progression and
metastasis of hepatocellular carcinoma (HCC). Circulating ANXA2 levels in HCC
patients are significantly higher compared with that of patients with benign
liver disease. ANXA2 levels have been found to correlate with hepatitis B virus
infection, extrahepatic metastasis and portal vein thrombus. By contrast, ANXA2
levels do not correlate with tumour size and AFP levels. However, the underlying
mechanisms of ANXA2 remain obscure. The results of the current study identified
that abnormalities in hepatic ANXA2 expression were localised to the cell
membrane and cytoplasm of HCC tissues and mainly in the cytoplasm of para
cancerous tissues. ANXA2 was overexpressed in MHCC97-H cells which have high
metastatic potential. Following specific ANXA2-small hairpin RNA (shRNA)
transfection in vitro, ANXA-2 was effectively inhibited and the S phase ratio of
cells was 27.76%, compared with 36.14% in mock-treated cells. In addition, the
invading cell ratio was reduced in the shRNA-treated group (52.16%) compared with
the mock-treated group (86.14%). The growth and volume of xenograft tumours in
vivo was significantly suppressed (P<0.05) in the shRNA group compared with that
of the mock group, indicating that ANXA2 may be a novel and useful target for
elucidating molecular mechanisms involving the proliferation and metastasis of
HCC.
PMID- 24348817
TI - Middle ear squamous papilloma: A report of four cases analyzed by HPV and EBV in
situ hybridization.
AB - Squamous papilloma involving the middle ear as a primary lesion is an extremely
rare occurrence. The aims of the present study were to investigate the presence
of human papilloma virus (HPV) and Epstein-Barr virus (EBV) infections in primary
middle ear squamous papilloma and to describe the clinical and pathological
features of the disease along with therapeutic strategies. A retrospective review
was conducted of four patients with clinical and pathological diagnoses of middle
ear squamous papilloma. In situ hybridization (ISH) for a wide range of HPV DNA
subtypes and EBV-encoded RNA was performed in the tissue samples obtained from
these patients. Only two cases of primary squamous papilloma in the middle ear
have been previously reported in the English literature. These papillomas
developed in males of ~60-years of age and otorrhea was the most frequent
complaint. Premalignant changes were observed in two of the present cases and ISH
of HPV and EBV was negative in all four cases. The results of the present study
indicated that chronic inflammatory stimulation, not HPV and EBV infection, is
involved in the occurrence of middle ear squamous papilloma and its malignant
transformation. Radical surgery and long-term postoperative follow-up are
recommended due to its malignant and recurrent potential. Further genetic
investigations with additional new cases are required to clarify the pathogenesis
of squamous papilloma involving the middle ear.
PMID- 24348816
TI - NANOG expression correlates with differentiation, metastasis and resistance to
preoperative adjuvant therapy in oral squamous cell carcinoma.
AB - NANOG protein, a transcription factor expressed in embryonic stem cells, is
overexpressed in tumor development. Although studies investigating the function
of NANOG in cancer have shown that it plays several roles, such as in cell
proliferation, invasion and metastasis, the overall function of NANOG in cancer
cells has remained elusive. In the present study, NANOG expression in oral
squamous cell carcinoma (OSCC) was examined to determine its potential clinical
significance. The expression of NANOG protein was assessed in 60 patients with
OSCC by immunohistochemistry, and its correlation with clinicopathological
factors and metastasis was evaluated. NANOG protein levels in human OSCC cell
lines were determined by western blotting and immunofluorescence staining. NANOG
protein expression was identified in 52 cases (86.7%) and expression levels were
higher in primary foci of poorly differentiated OSCC than in those of well
differentiated OSCC, indicating that NANOG expression is associated with OSCC
differentiation. Regardless of the differentiation levels of primary foci, NANOG
expression levels in metastatic foci were extremely high. In addition, NANOG
expression in metastatic foci was maintained at high levels following
preoperative adjuvant therapy. Furthermore, NANOG protein was detected at an
identical level in human OSCC cell lines. These data indicate that NANOG
expressing OSCC cells tend to metastasize and that metastatic tumors expressing
NANOG may be resistant to preoperative adjuvant therapy, including
chemoradiation. Thus, assessment of NANOG expression may assist the strategy for
treatment of OSCC metastasis.
PMID- 24348818
TI - Complete remission of a reccurrent mesenteric liposarcoma with rare histological
features following the administration of trabectedin.
AB - The present study describes a rare case of a mesenteric liposarcoma that resulted
in a complete remission (CR) following treatment with trabectedin (Yondelis(r)).
The patient presented with abdominal pain and fever. An abdominal mass was
identified that corresponded to a mixed-type high-grade mesenteric liposarcoma
with wide areas of necrosis, areas of dedifferentiation and features of a
leiomyosarcoma. Three months after the removal of the first mass, the patient
underwent a second laparotomy, followed by treatment with doxorubicin and
ifosfamide. Subsequently, the patient was started on therapy with trabectedin and
a CR was noted following only four cycles of therapy. The best responses that are
reported in the literature for cases of liposarcoma treated with trabectedin are
mostly for liposarcomas of the myxoid/round cell type and are mainly partial
responses. In the present study, trabectedin was used for the treatment of a
mesenteric liposarcoma of mixed morphological features and a CR was achieved.
PMID- 24348819
TI - Sustained complete response of hepatocellular carcinoma with portal vein tumor
thrombus following discontinuation of sorafenib: A case report.
AB - Hepatocellular carcinoma (HCC) is the third most common cause of cancer
associated mortality worldwide. No effective treatment has been established for
unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi
targeted tyrosine kinase inhibitor for unresectable advanced HCC that
significantly improves progression-free and overall survival. However, in the two
large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of
complete response (CR) were reported. The present study reports the case of a 68
year-old male with hepatitis C virus-related cirrhosis and multiple recurrent
HCCs, with a tumor thrombus of the third portal vein following resection. The
patient received 400 mg once daily (half the standard dose) of sorafenib for two
years and achieved a CR. At the most recent follow-up examination at one year
after the cessation of treatment, the patient was observed to be in remission
without clinical or imaging evidence of disease recurrence.
PMID- 24348820
TI - Occult neoplastic cells in lymph node sinuses and recurrence/metastasis of stage
II/III gastric cancer.
AB - In the present study, we investigated the correlation between the presence of
occult neoplastic cells (ONCs) in lymph node sinuses and recurrence/metastasis of
stage II/III gastric cancer in 164 patients who underwent radical curative
resection. We calculated the five-year relapse-free survival rate (5Y-RFS) and
five-year overall survival rate (5Y-OS) of the ONC(+) and ONC(-) groups. The 5Y
RFS was 71.4% in the ONC(-) group and 47.5% in the ONC(+) group (P=0.003). The 5Y
OS was 68.8 and 48.4%, respectively (P=0.008). ONCs were found in 34.8% of stage
II patients and were also detected in 66.7% of stage III patients. For
distinguishing between the recurrence and non-recurrence groups, the sensitivity
of ONC(+) was 64.5% (40/62; P=0.003), the positive predictive value (PPV) was
49.4% (40/81), the specificity was 59.8% (61/102) and the negative predictive
value (NPV) was 73.5% (61/83). This high sensitivity indicates that ONC
positivity may be a significant indicator for high-risk patients in the early
postoperative period, and a lack of ONCs may be a useful indicator for
identifying low-risk patients, as patients without ONCs had a high NPV.
PMID- 24348821
TI - Expression of p-Akt in ovarian serous carcinoma and its association with
proliferation and apoptosis.
AB - The aim of the present study was to determine the expression of p-Akt in ovarian
serous carcinoma (OSC) and its association with proliferation and apoptosis.
Paraffin-embedded tissues of patients aged between 35 and 64 years old without
history of radiotherapy, chemotherapy and hormone therapy prior to surgery were
collected. In total, samples included 12 ovarian serous cystadenomas (OSAs), 18
ovarian serous borderline tumors (OS-BTs) and 46 OSCs. Of the 46 OSC samples, 16
were well-differentiated, 20 were moderately differentiated and 10 were poorly
differentiated, while 22 developed lymphatic metastases and 24 were metastasis
free. An additional 10 paraffin-embedded normal ovarian tissues (NOTs) were used
as controls. Streptavidin-peroxidase immunohistochemistry assays were used to
investigate the expression of p-Akt and cyclin D1 in the collected samples.
Compared with NOT, p-Akt expression in the OS-BT and OSC groups, as well as
cyclin D1 expression in the OSA and OSC groups, was significantly elevated
(P<0.05). Compared with the OSA group, p-Akt expression in the OSC group was
significantly elevated (P<0.01) and reversely associated with tumor
differentiation (P<0.01), whereas cyclin D1 expression showed no correlation with
tumor differentiation (P>0.05). The expression of p-Akt, caspase-3 and cyclin D1
was positively associated with lymphatic metastasis (r=0.334; P=0.023). The
expression of p-Akt gradually increased with carcinoma development and was
associated with differentiation and metastasis of OSC, revealing that the
activation of the PI3K/Akt signaling pathway is involved in the development of
OSC. Furthermore, the expression of cyclin D1 gradually increased in the NOT,
OSA, OS-BT and OSC groups and was associated with tumor metastasis.
PMID- 24348822
TI - Signet-ring cell melanoma with sentinel lymph node metastasis: A case report with
immunohistochemical analysis and review of the clinicopathological features.
AB - Signet-ring cell melanoma is an extremely rare variant of malignant melanoma. A
68-year-old male presented with a black nodule on the left thigh.
Histopathological examination revealed proliferation of sheet-like or variable
sized nests of atypical melanocytes. Neoplastic cells showing signet-ring cell
appearance, characterized by the presence of eccentrically located enlarged
nuclei and abundant pale cytoplasm, were also present. Immunohistochemically, the
tumor cells were positive for S-100 protein, vimentin and Melan-A. Moreover,
mammalian target of rapamycin (mTOR) pathway proteins were diffusely expressed.
The current case report presents the 21st reported case of signet-ring cell
melanoma. Analyses of the clinicopathological features revealed that this disease
commonly affects middle-aged males and the presence of metastatic signet-ring
cell melanoma with an unknown primary tumor. Immunohistochemical analyses of
melanocytic markers have been useful for establishing the diagnosis of this type
of disease, however, HMB-45 is occasionally found to be negative. In addition,
the present case report is the first to analyze the expression of mTOR pathway
proteins, which are central proteins involved in carcinogenesis and its inhibitor
has been proposed as a therapeutic target for various types of tumor. Therefore,
the mTOR inhibitor may also be a potential candidate for the treatment of this
type of tumor.
PMID- 24348823
TI - Epigenetic silencing of checkpoint with fork-head associated and ring finger gene
expression in esophageal cancer.
AB - Checkpoint with fork-head associated and ring finger (CHFR) is a mitotic
checkpoint gene with tumor-suppressor functions. Previous studies have described
the hypermethylation of the CpG island in the promoter region as a key mechanism
involved in silencing tumor suppressor genes. The epigenetic alterations
regulating CHFR expression and the clinical significance of CHFR downregulation
remain unclear. A total of 40 patients with esophageal squamous cell carcinoma
who underwent primary resection were enrolled in this study. CHFR mRNA expression
was quantified, followed by an evaluation of the methylation status using
methylation-specific polymerase chain reaction (MSP) techniques in 29 patients.
The correlation between CHFR expression and MSP status was then analyzed. In
addition, the significance of CHFR expression was determined, with respect to
clinicopathological features and overall survival. Aberrant hypermethylation of
the CHFR gene was observed in 13 of 29 primary esophageal cancers. The CHFR
expression levels of the methylated status samples was significantly lower than
that of the unmethylated status samples (P=0.014). CHFR expression levels did not
exhibit clinical significance with respect to the patient characteristics or
overall survival. Hypermethylation of the CHFR gene is a common event in the
development of primary esophageal cancer. CpG island hypermethylation of the
promoter region in the CHFR gene is a key mechanism involved in silencing the
CHFR gene in patients with esophageal cancer.
PMID- 24348824
TI - Frizzled-2: A potential novel target for molecular pancreatic cancer therapy.
AB - In the present study, pancreatic cancer cell proliferation was analyzed following
the suppression of frizzled (Fz)2 expression. Reverse transcription polymerase
chain reaction (PCR) was performed using RNA isolated from pancreatic cancer cell
lines, PANC-1, NOR-P1, PK-45H, PK-1, PK-59, MIA-Paca2 and KP4. A surgical
specimen of pancreatic cancer was immunostained with antibodies specific to Fz2.
Cell proliferation assays were performed with MIA-Paca2 cells transfected with
small interfering RNA (siRNA) or short hairpin RNA (shRNA) of Fz2. Fz2 was found
to be expressed in all pancreatic cancer cell lines, with the exception of NOR
P1. Immunostaining revealed that Fz2 was not expressed in normal pancreatic
tissues, while it was expressed in pancreatic cancer cells. The expression levels
of cyclin D1 were analyzed by quantitative PCR. The proliferation and expression
of cyclin D1 were suppressed with the siRNA and shRNA of Fz2 in the MIA-Paca2
cells. Therefore, Fz2 is a potential target for the molecular therapy of
pancreatic cancer.
PMID- 24348825
TI - Primary bone marrow diffuse large B-cell lymphoma accompanying cold agglutinin
disease: A case report with review of the literature.
AB - Cold agglutinin disease (CAD) is a well-recognized complication of
lymphoproliferative disorders. It has been previously recognized that cases of
primary CAD frequently exhibit underlying malignant lymphoma in the bone marrow.
Lymphoplasmacytic lymphoma is the most common subtype of malignant lymphoma;
however, diffuse large B-cell lymphoma (DLBCL) has also been documented, albeit
extremely rare. The current report presents a case of primary bone marrow DLBCL
accompanying CAD. A 76-year-old male presented with fever and fatigue. Laboratory
tests revealed anemia and elevated bilirubin and cold agglutinins with a titer of
8,192 at 4 degrees C. Bone marrow biopsy demonstrated DLBCL and systemic
surveillance failed to detect tumorous lesions or lymphadenopathy. Following R
THP-COP therapy, cold agglutinins titer was markedly decreased (by <4); however,
malignant lymphoma relapsed and cold agglutinin levels increased again (4,096).
This is the second documented case of primary bone marrow DLBCL accompanying CAD.
Previously, malignant lymphoma exclusively involving the bone marrow, namely
primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive
subtype. The analyses of the present study revealed that the incidence of
hemolytic anemia in primary bone marrow DLBCL may be high compared with
conventional DLBCL. Therefore, additional analyses are required to clarify the
clinicopathological features of PBML.
PMID- 24348826
TI - Interaction of a CD44+ head and neck squamous cell carcinoma cell line with a
stromal cell-derived factor-1-expressing supportive niche: An in vitro model.
AB - The cancer stem cell (CSC) theory implies that CSCs are surrounded by supportive
stromal cells, which are known as the CSC niche. Stromal cell-derived factor-1
(SDF-1) shows a multitude of functional effects in head and neck squamous cell
carcinoma (HNSCC) cells, including migration and polarization. Therefore, the SDF
1-CXCR4 axis may be involved in the pathophysiology of the progression,
recurrence and metastasis of malignant diseases of the head and neck. In the
present study, the CD44+ HNSCC UM-SCC-11A cell line was used as a model for CSCs.
The interaction between the UM-SCC-11A cells and the supportive
microenvironmental cells, including fibrocytes, human umbilical vein endothelial
cells (HUVECs) and human microvascular vein endothelial cells (HMVECs) was
evaluated. All the cell types that were tested were shown to secrete different
concentrations of SDF-1 into the surrounding culture medium [mean (m)fibro,
1243.3+/-156.2 pg/ml; mHMVEC, 1061.4+/-23.2 pg/ml; mHUVEC, 849.6+/-110.9 pg/ml].
The migration of the UM-SCC-11A cells towards the supportive cells was increased
by a higher supply of SDF-1 (contrfibro, 315.23+/-61.55 MUm; mfibro, 477.73+/
143.7 MUm; Pfibro=0.003; contrHMVEC, 123.41+/-66.68 MUm; mHMVEC, 249.04+/-111.95
MUm; PHMVEC=0.004; contrHUVEC, 189.7+/-93.26 MUm; mHUVEC, 260.82+/-161.58 MUm).
The amount of the UM-SCC-11A cells that migrated towards the differentiated
fibrocytes was significantly higher than that which migrated towards the HMVECs
or HUVECs (Pfibro/HMVEC=2.12E-11; Pfibro/HUVEC=2.28E-5). Cell-cell interaction by
podia formation of the UM-SCC-11A cells was observed in all the supportive cell
types that were tested. Broadly based cell-cell contacts were observed. By
contrast, digitiform podia formations presented by the UM-SCC-11A cells were
determined using fluorescence microscopy. The SDF-1-CXCR4 axis is postulated to
be a crucial pathway in the interaction between CSCs and their surrounding
supportive cells. Understanding the cell-cell interactions in the CSC niche using
in vitro models may aid in gaining further insight into these mechanisms and
finding new strategies of therapy in this field.
PMID- 24348827
TI - Treatment with Huisheng oral solution inhibits the development of pulmonary
thromboembolism and metastasis in mice with Lewis lung carcinoma.
AB - The aim of this study was to investigate whether Huisheng oral solution (HSOS)
has an inhibitory effect on the development of pulmonary thrombosis and
metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible
mechanisms involved. A mouse model of LLC was developed, and model mice were
divided into either a treatment group or a control group to undergo treatment
with HSOS or normal saline. Normal mice treated with saline were used as normal
controls. On day 25 after treatment, blood samples were drawn from the eyes of
half the mice in each group to determine blood cell counts and plasma levels of D
Dimer and vascular endothelial growth factor (VEGF), while heart blood samples
were collected from the remaining mice to measure the rate of thrombin-induced
platelet aggregation. For all mice, pathological analyses of the cerebrum, lung,
mesentery, femoral vein, external iliac vein and spleen were performed. Tumors
were weighed to assess the impact of HSOS treatment on tumor growth, and the
number of thrombi, metastatic nodules and neovessels in the tumor tissue were
counted. In addition, 24 normal New Zealand rabbits were divided into two groups
and treated with either HSOS or normal saline to determine the rates of ADP-,
collagen- or thrombin-induced platelet aggregation. Compared with the model
group, HSOS treatment decreased the incidence of pulmonary thromboembolism and
metastasis, the number of metastatic nodules, the plasma levels of D-dimer and
VEGF, the rate of collagen-induced platelet aggregation in rabbits and the
numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the
thymus and spleen coefficients and the number of platelets (P<0.05 for all), but
had no significant effect on thrombin-induced platelet aggregation in mice and
rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood
cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS
treatment effectively reduced the development of pulmonary thromboembolism and
metastasis in mice bearing LLC via mechanisms possibly associated with
ameliorating a blood hypercoagulable state, decreasing tumor angiogenesis and
enhancing immunity.
PMID- 24348828
TI - Correlation between TSP-1, TGF-beta and PPAR-gamma expression levels and glioma
microvascular density.
AB - Gliomas are the most common type of primary tumor in the central nervous system
and are characterized by abundant capillary angiogenesis. It is important to
study the underlying molecular mechanisms of angiogenesis in order to aid the
identification of potential therapeutic targets. The aim of the current study was
to investigate the expression levels of thrombospondin-1 (TSP-1), transforming
growth factor-beta (TGF-beta) and peroxisome proliferator-activated receptor
gamma (PPAR-gamma) in gliomas, and determine their relationships with
angiogenesis. Immunohistochemical methods were used to detect TSP-1, TGF-beta and
PPAR-gamma expression levels and to assess microvascular density (MVD) in 99
glioma tissue samples of various grades. The total positive expression rates of
TSP-1 and PPAR-gamma were 78.4 and 94.1% in low-grade gliomas and 45.8 and 39.6%
in high-grade gliomas. These values suggest that their expression negatively
correlated with tumor grade. However, TGF-beta expression positively correlated
with tumor grade; the total positive expression rate of TGF-beta in high-grade
gliomas (93.8%) was significantly increased compared with that in low-grade
gliomas (43.1%). The MVD in the low-grade group was 28+/-7.2 vessels/field, which
was significantly lower than in the high-grade group (45+/-6.2 vessels/field).
TSP-1 and PPAR-gamma expression levels were negatively correlated with MVD
(P<0.05), while the TGF-beta expression level was positively correlated with MVD
(P<0.05). These results indicate that the TSP-1, TGF-beta and PPAR-gamma
expression levels in gliomas are correlated with MVD, which suggests that these
proteins may be involved in the regulation of glioma angiogenesis.
PMID- 24348829
TI - Knockdown of astrocyte elevated gene-1 inhibits growth through suppression of IL
6 secretion in HepG2 human hepatoma cells.
AB - Astrocyte-elevated gene-1 (AEG-1) has been reported to be associated with cancer
progression in various types of human cancers, including liver cancer. However,
to date, the molecular mechanism of AEG-1 action on the growth of liver cancer
cells has been poorly elucidated. The present study aimed to investigate the
effect of AEG-1 on the proliferation and apoptosis of liver cancer cells and the
role of IL-6 in this process using the HepG2 human hepatoma cell line. shRNAs
targeting AEG-1 were used to silence the expression of AEG-1. The effects on cell
growth were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
bromide, colony formation and cell cycle assays. Apoptosis was analyzed by flow
cytometry. The expression of IL-6 was examined by quantitative polymerase chain
reaction and enzyme-linked immunosorbent assay, and the phosphorylation of Stat3
was detected by western blotting. AEG-1 knockdown was observed to induce cell
proliferation inhibition and apoptosis through the suppression of IL-6 secretion.
Stat3, a downstream target of IL-6 signaling, was suppressed in the AEG-1
silenced cells and target genes, including Bcl-2 and crystalin, alphaB, which are
associated with cell survival, were downregulated. Overall, the findings suggest
that aberrant AEG-1 expression promotes the growth of HepG2 liver cancer cells,
contributing to the progression of liver cancer, which may partly be mediated by
IL-6 signaling.
PMID- 24348830
TI - Semi-automated evaluation of Ki-67 index in invasive ductal carcinoma of the
breast.
AB - A significant factor that affects the value of the Ki-67 proliferation index (IK)
is the interpretation and implementation approach. This method is based on visual
or automated methods to count tumor nuclei labeled with Ki-67 antigen, and is
prone to errors. Detection of Ki-67 is a useful tool in breast cancer and
contributes to its molecular classification. The current study proposes a method
for the quantification of Ki-67-positive tumor nuclei, which allows for the
determination of the exact IK value that is required for tumor stratification
based on the proliferation rate. The IK was assessed in 81 successive cases of
diagnosed invasive ductal breast carcinoma using a semi-automated method that
accurately identifies positive tumor cell nuclei. This method prevents the
inclusion of other possible positive cells, including lymphoid, normal epithelia
and hyperplastic. In small specimens with increased cell density, where the
nucleus/cytoplasm ratio is markedly in favor of the nucleus and the distance
between nuclei is small, the method allows precise quantification of the nuclei,
even when the limits between nuclei are difficult to identify. In addition,
images may be stored in a database, including the assessments, and easily
accessed when required. We hypothesize that the semi-automated method for
counting nuclei offers the most accurate method of assessing the IK and avoids
counting errors that may occur through other methods.
PMID- 24348831
TI - Nucleosome-binding protein HMGN2 exhibits antitumor activity in oral squamous
cell carcinoma.
AB - Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) serve as effectors
in the antitumor response. High mobility group nucleosomal binding domain 2
(HMGN2) is a candidate effector molecule involved in CTL and NK cell function. In
the current study, recombinant human HMGN2 was isolated and purified from
transformed Escherichia coli. Tca8113 cells, an oral squamous cell carcinoma
line, were treated with a variety of HMGN2 protein concentrations and cell growth
was analyzed. HMGN2 significantly inhibited the growth of Tca8113 cells and was
predicted to arrest cells in the S phase. Moreover, HMGN2 treatment increased the
apoptosis rate of Tca8113 cells. Western blotting indicated the upregulation of
p53 and Bax proteins, whereas Bcl-2 was significantly downregulated. In addition,
caspase-3 was found to be activated. Furthermore, the HMGN2 protein may suppress
the growth of Tca8113 cells in vivo. The results of the current study indicated
that the HMGN2 protein may inhibit the growth of oral squamous cell carcinoma and
HMGN2 may represent an antitumor effector molecule of CTL or NK cells.
PMID- 24348832
TI - VX680 suppresses the growth of HepG2 cells and enhances the chemosensitivity to
cisplatin.
AB - VX680 is an Aurora A inhibitor. It has been reported to inhibit the growth of the
HepG2 cell line in several studies. However, whether it enhances chemosensitivity
to cisplatin remains unclear. In this study, the synergistic effect of VX680 and
cisplatin on the proliferation of HepG2 cells was determined by MTT assay. The
changes in cell apoptosis were detected by flow cytometry. Aurora A, Bcl-2 and
p53 protein levels were analyzed by western blotting. This study demonstrated
that VX680, cisplatin and a combination of the two inhibit the growth of HepG2
cells in a dose- and time-dependent manner. A synergistic effect was observed
with the combined therapy. Moreover, the inhibitory effect of VX680 was
positively correlated with the expression of Aurora A. The rate of apoptosis in
the combined group was significantly higher compared with that of the VX680 and
cisplatin groups. In addition, VX680 and cisplatin increased the expression of
the p53 protein. Cisplatin reduced the expression of Bcl-2 protein, while VX680
did not. In the combined group, the expression of Bcl-2 and p53 changed
significantly compared with the single drug group and control group. This study
suggests that Aurora A may represent a valid target in hepatocellular carcinoma.
We also demonstrated that the Aurora A inhibitor VX680 has a synergistic effect
with cisplatin.
PMID- 24348833
TI - Low dose of interferon-alpha improves the clinical outcomes of docetaxel in
patients with castration-resistant prostate cancer: A pilot study.
AB - The aim of this study was to test whether a low dose of interferon-alpha-2b (IFN
alpha2b) enhances the clinical outcome of docetaxel (DXT) in patients with
castration-resistant prostate cancer (CRPC). A prospective controlled trial of 40
CRPC patients receiving 5 mg of prednisone twice daily was conducted, where
patients were randomly assigned to be administered 75 mg/m2 DXT plus 3 mIU/m2 IFN
alpha2b (group A, n=20) or 75 mg/m2 DXT alone (group B, n=20). The prostate
specific antigen (PSA) response, tumor response, progression-free survival (PFS)
and overall survival (OS) were evaluated. There was no statistically significant
difference in PSA response rate between groups A and B (65 vs. 47.4%, P=0.341).
The tumor response rate in group A was significantly greater compared with that
in group B (55 vs. 21.1%, P=0.048). The median PFS was longer in group A compared
with that in group B (10 vs. 8 months, P=0.043). There was no statistically
significant difference in median OS between the two groups (19 vs. 17 months,
P=0.348), but one patient displayed a complete tumor response in group A. In
groups A and B, transient grade 3 to 4 neutropenia was observed in nine and six
patients, grade 3 to 4 anemia was observed in three and five patients, and grade
3 to 4 general fatigue was observed in four and one patient(s), respectively. The
proportion of patients with grade 3 to 4 toxicity was not statistically different
between the two groups. A low dosage of IFN-alpha2b may improve the antitumor
activity of DXT with an acceptable toxicity profile in patients with CRPC.
PMID- 24348834
TI - Expression of dedifferentiation markers and multilineage markers in U251
glioblastoma cells with silenced EGFR and FGFR genes.
AB - Epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF), and
their receptors, epithelial growth factor receptor (EGFR) and bFGF receptor
(bFGFR), are frequently overexpressed in high-grade gliomas. In the present
study, the EGF and bFGF levels in U251 glioblastoma cell culture supernatants
were determined by ELISA, and enhanced green fluorescent protein (EGFP)-labeled
recombinant lentiviral expression vectors with small interfering RNA targeting
the EGFR and bFGFR genes were constructed. The mRNA expression levels of EGFR,
bFGFR, cluster of differentiation (CD)133, glial fibrillary acidic protein
(GFAP), tubulin-beta3 (TUBB3) and myelin basic protein (MBP) were determined
using quantitative polymerase chain reactions in U251 cells prior to and
following silencing of the EGFR and/or bFGFR genes. Prior to silencing, the U251
cells secreted EGF and bFGF, and expressed EGFR, bFGFR, CD133, GFAP, TUBB3 and
MBP mRNA. Subsequent to silencing the EGFR and/or bFGFR gene, CD133 mRNA
expression decreased and GFAP and TUBB3 mRNA expression increased. Silencing the
EGFR and FGFR genes acted synergistically to downregulate CD133 expression. The
downregulation of CD133 mRNA expression and the upregulation of GFAP and TUBB3
mRNA expression were not significantly different when blocking the EGFR and FGFR
pathways. These results indicate that autocrine or paracrine EGF and/or FGF
mechanisms exist in U251 cells. Knocking down the EGFR and/or FGFR genes
downregulates CD133 mRNA expression and facilitates glial and neuronal
differentiation in U251 cells.
PMID- 24348835
TI - Primary pleomorphic rhabdomyosarcoma of the adrenal gland in an adult: A case
report.
AB - A 61-year-old female was referred to The First Affiliated Hospital, College of
Medicine, Zhejiang University (Hangzhou, China) due to a right adrenal tumor. A
pre-operative transcutaneous fine-needle aspiration biopsy and right
adrenalectomy were performed, and pathological analysis resulted in the diagnosis
of pleomorphic rhabdomyosarcoma (RMS). Primary pleomorphic RMS of the adrenal
gland in an adult is a rare condition. To the best of our knowledge, this is the
first case of pleomorphic RMS of the adrenal gland in an adult diagnosed by light
microscopy and immunohistochemical stains.
PMID- 24348836
TI - Primary giant mediastinal synovial sarcoma of the neck: A case report and review
of the literature.
AB - Synovial sarcomas commonly occur in the soft tissue of the extremities, while a
primary occurrence in the mediastinum is quite rare. The current study reports
the case of an 11-year-old male who presented with a neck mass, which computed
tomography showed was due to a giant mediastinal mass involving the thyroid
gland. The tumor was resected by thoracotomy and diagnosed as monophasic synovial
sarcoma by histopathology. The patient received adjuvant combination chemotherapy
and radiation therapy following surgery. At the 3-month follow-up, no local tumor
recurrence was found. The present case report highlights the significance of
recognizing the unusual presentation and clinical manifestation of synovial
sarcoma to aid clinical management. Written informed consent was obtained from
the patient's family.
PMID- 24348837
TI - Granulocytic sarcoma of the breast in acute myeloid leukemia: Two case reports.
AB - Granulocytic sarcoma (GS) of the breast is extremely rare in patients with acute
myeloid leukemia (AML) and therefore, is often misdiagnosed as lymphoma or other
benign tumors. The current report presents two cases of GS of the breast, of
which, one was considered to be a fibroma, as observed by fine-needle aspiration,
and the other was misdiagnosed as lymphoma by frozen section. Previous literature
that described the clinical and pathological characteristics, treatments and
prognosis of GS of the breast in AML were reviewed. In addition to the treatment
of mastectomy with/without radiotherapy, lumpectomy may also be received as a
good treatment plan.
PMID- 24348838
TI - Management of perivascular epithelioid cell tumor of the liver: A case report and
review of the literature.
AB - Perivascular epithelioid cell tumor (PEComa) is a rare tumor that originates from
mesenchymal tissues. Cases of PEComa in the liver are extremely rare. The present
study aimed to analyze the clinical features of PEComa in the liver and discuss
its management. Here we report a 25-year-old female with multiple lesions of low
density with poorly defined borders in the liver, as shown by a computed
tomography (CT) scan. A partial hepatectomy was proceeded and PEComa was
diagnosed by immunohistochemistry. No evidence of recurrence was observed during
the one year follow-up. A total of 20 patients with hepatic PEComa, including one
case from the present study and 19 cases that were reported in literature between
June 2001 and December 2012, were reviewed and analyzed. The mean patient age was
43.4 years (range, 25-67 years) and the cases consisted of 18 female and two male
patients. The tumor size ranged between 2.0*1.6 and 15.0*12.0 cm. Of the 20
patients, nine were asymptomatic and 11 had mild to significant complaints.
Immunohistochemistry plays a key role in the diagnosis of PEComa. All the cases
in this study were strongly positive for human melanoma black-45. A surgical
resection is the gold standard for curative intent. All the patients underwent a
surgical resection and none were administered perioperative chemotherapy or
radiotherapy. In total, 13 of the 14 patients with follow-up information survived
during the 8-36-month follow-up period and one patient succumbed due to
recurrence two years after the surgery.
PMID- 24348839
TI - Rectal adenocarcinoma metastatic to the tonsil; PET-CT observations with
pathological confirmation: A case report.
AB - Metastasis of rectal adenocarcinoma develops by lymphatic or hematogenous spread.
The usual sites of metastasis from rectal adenocarcinoma include local and
distant lymph nodes, the liver and the lungs. The current case report presents a
unique case of a mass that was identified in the tonsil by positron emission
tomography-computed tomography (PET-CT), indicating a metastasis from rectal
adenocarcinoma. Metastatic tumor to the tonsil is extremely rare and to the best
of our knowledge, no previous studies have reported a case of tonsil metastasis
from rectal adenocarcinoma. PET-CT scanners represent an important evolution in
technology that is helping to bring anatomical imaging togeother with functional
imaging in cancer diagnosis and therapy. Written informed consent was obtained
from the patient.
PMID- 24348840
TI - Primary breast T-cell lymphoma, unspecified, treated with autologous peripheral
blood stem cell transplantation: A case report and literature review.
AB - The current study presents a case of primary T-cell lymphoma (PTBL), unspecified,
in a 27-year-old female. The patient received chemotherapy [cyclophosphamide,
epirubicin, vindesine and prednisolone (CHOP) and VP-16 plus CHOP (ECHOP)] and
autologous peripheral blood stem cell transplantation, however, relapse occurred
rapidly. The recurrent tumor exhibited increased levels of karyopyknosis and
nuclear fragmentation and a higher Ki67 index compared with the primary tumor. No
response to subsequent chemotherapy, including ECHOP and gemcitabine,
dexamethasone and cisplatin, was observed. The patient succumbed to PTBL,
unspecified, 18 months after the diagnosis. We hypothesize that autologous
peripheral blood stem cell transplantation is ineffective for PTBL.
PMID- 24348841
TI - Expression of gammaH2AX in various gastric pathologies and its association with
Helicobacter pylori infection.
AB - Phosphorylation of H2AX at Ser 139 (gammaH2AX) is a biomarker of DNA double
strand breaks (DSBs). The present study aimed to explore the association between
gammaH2AX levels and gastric pathology and Helicobacter pylori (H. pylori)
infection. Gastric biopsies were obtained from 302 H. pylori-negative and
positive patients, including those with chronic gastritis (CG), intestinal
metaplasia (IM), dysplasia (Dys) and gastric cancer (GC). Proteins were extracted
from five gastric epithelial cell lines and from 10 specimens of matched GC and
adjacent normal tissues. The expression of gammaH2AX, a biomarker for the
detection of DNA DSBs, in gastric tissues was detected by immunohistochemistry
and western blotting. The expression of gammaH2AX progressively increased in
tissues according to pathological stage from CG to Dys, but was slightly
decreased in GC. H. pylori infection was associated with increased gammaH2AX
expression, IM and Dys. Overexpression of gammaH2AX in GC was found to correlate
with tumor location, gross appearance, differentiation, depth of invasion, TNM
stage and lymph node metastasis. The results indicated that DSBs appear to be an
early molecular event in gastric carcinogenesis, which may be associated with H.
pylori infection. Moreover, immunohistochemical staining of gammaH2AX was found
to correlate with a number of clinicopathological characteristics. The expression
of gammaH2AX may serve as a valuable biomarker for the diagnosis and progression
of GC.
PMID- 24348842
TI - Requirement for a standardised definition of advanced gastric cancer.
AB - Each year, ~988,000 new cases of stomach cancer are reported worldwide.
Uniformity for the definition of advanced gastric cancer (AGC) is required to
ensure the improved management of patients. Various classifications do actually
exist for gastric cancer, but the classification determined by lesion depth is
extremely important, as it has been shown to correlate with patient prognosis;
for example, early gastric cancer (EGC) has a favourable prognosis when compared
with AGC. In the literature, the definition of EGC is clear, however, there is
heterogeneity in the definition of AGC. In the current study, all parameters of
the TNM classification for AGC reported in each previous study were individually
analysed. It was necessary to perform a comprehensive systematic literature
search of all previous studies that have reported a definition of ACG to
guarantee homogeneity in the assessment of surgical outcome. It must be
understood that the term 'advanced gastric cancer' may implicate a number of
stages of disease, and studies must highlight the exact clinical TNM stages used
for evaluation of the study.
PMID- 24348843
TI - Icotinib combined with rapamycin in a renal transplant recipient with epidermal
growth factor receptor-mutated non-small cell lung cancer: A case report.
AB - As kidney transplant recipients are at increased risk of developing cancer,
regular monitoring should be undertaken to monitor the balance between
immunosuppression and graft function and to identify malignancy. The present
study reports the outcome of the treatment of adenocarcinoma of the lung
(T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year
old male renal transplant patient receiving rapamycin and prednisolone as ongoing
renal immunosuppressive therapy. An initial partial response to icotinib was
achieved, and graft function remained good. However, the patient subsequently
developed interstitial pneumonitis. The plasma concentrations of rapamycin and
icotinib were within the normal ranges, which excluded the possibility of a
pharmacokinetic drug interaction and indicated that the interstitial pneumonitis
was likely to be associated with the side-effects of icotinib. Drug therapy was
discontinued and the patient underwent a segmentectomy. Tacrolimus was
administered for ongoing renal graft immunosuppression. To the best of our
knowledge, this is the first report of the concomitant administration of icotinib
and rapamycin in post-transplant de novo lung cancer. It is also the first report
of interstitial pneumonitis associated with icotinib in a post-transplant
patient.
PMID- 24348844
TI - Treatment outcomes in relapsed acute promyelocytic leukemia patients initially
treated with all-trans retinoic acid and arsenic compound-based combined
therapies.
AB - Contemporary combined therapies that include the use of all-trans retinoic acid
(ATRA) and arsenic compounds have reduced relapse rates from ~50 to <10% in acute
promyelocytic leukemia (APL) patients, however relapse treatment remains
controversial. Treatment outcomes in relapsed patients with APL previously
treated with combined ATRA + arsenic compound therapy were investigated. A
retrospective, observational study was conducted of 25 patients with APL (male to
female ratio, 17:8; mean age, 36.4+/-10.3 years) exhibiting first-time relapse
following combined ATRA + arsenic compound therapy. These patients were
subsequently treated with secondary ATRA + arsenic compound therapy, salvage
chemotherapy, monoclonal antibody therapy or intrathecal chemotherapy, between
January 1994 and December 2010. The overall remission rate, duration of remission
and toxic effects were assessed. Patient outcomes included mortality during
secondary induction therapy (6/25, 24.0%); complete recovery from central nervous
system (CNS) relapse following intrathecal chemotherapy (1/25, 4.0%); complete
remission following ATRA + arsenic compound therapy (10/25, 40.0%), chemotherapy
(3/25, 12.0%) and targeted therapy (1/25, 4.0%); and non-remission (NR) following
ATRA + arsenic compound therapy (4/25, 16%). Four (16.0%) patients were
subsequently treated with allogeneic hematopoietic stem cell transplantation
(allo-HSCT), two of which remained disease-free at the end of the study period
and two of which succumbed to the disease. Secondary bone marrow and CNS relapse
occurred in 14 (56.0%) patients and one (4.0%) patient, respectively. ATRA +
arsenic compound-based combination therapy was effective in re-inducing
morphological remission in relapsed patients with APL with previous exposure to
ATRA + arsenic compounds, producing low molecular remission rates and high risk
of secondary relapse. Furthermore, investigation of early allo-HSCT is required
to determine its potential as a therapeutic option for re-inducing morphological
remission in relapsed patients with APL with previous exposure to ATRA + arsenic
compounds.
PMID- 24348845
TI - microRNA-106a modulates cisplatin sensitivity by targeting PDCD4 in human ovarian
cancer cells.
AB - microRNAs (miRNAs/miRs) are a cluster of short non-protein coding RNAs that
negatively regulate gene expression, which is involved in fundamental cellular
processes, including the response of tumor cells to chemotherapeutic agents. The
present study investigated the role of miR-106a in the development of drug
resistance in ovarian cancer cells. The expression of miR-106a in the ovarian
cancer OVCAR3 cell line and the cisplatin (CDDP)-resistant ovarian cancer
OVCAR3/CIS cell line was detected using stem-loop quantitative (q)PCR. The OVCAR3
and OVCAR3/CIS cells were transfected with mimics or inhibitors of miR-106a or
with negative control (NC) RNA using lipofectamine 2000. Luciferase reporter
assays were used to determine whether PDCD4 was a direct target of miR-106a in
the OVCAR3 cells. The expression levels of the PDCD4 proteins were assessed using
qRT-PCR and western blotting, respectively. Drug sensitivity was analyzed using a
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while
apoptosis was determined by fluorescence-activating cell sorting analysis. The
expression levels of miR-106a were upregulated in the CDDP-resistant ovarian
cancer OVCAR3/CIS cell line compared with the parental OVCAR3 cell line. However,
the PDCD4 protein levels were decreased in the OVCAR3/CIS cells compared with the
OVCAR3 cells. The luciferase reporter assays revealed that PDCD4 was a direct miR
106a target in the OVCAR3 cells. Transfection of the OVCAR3/CIS cells with
inhibitors of miR-106a enhanced the sensitivity of the OVCAR3/CIS cells to CDDP
and increased CDDP-induced apoptosis. The expression of the PDCD4 protein and the
sensitivity to CDDP was decreased in the OVCAR3 cells that were transfected with
the mimics of miR-106a. The knockdown of PDCD4 expression using PDCD4-specific
siRNAs in the OVCAR3 cells demonstrated that PDCD4 is a key signaling molecule in
OVCAR3 cell CDDP-induced resistance. miR-106a may be involved in the development
of drug resistance and the regulation of PDCD4 expression, at least in part, by
modulating CDDP-induced apoptosis in ovarian cancer cells.
PMID- 24348846
TI - Paxillin expression is closely linked to the pathogenesis, progression and
prognosis of gastric carcinomas.
AB - Paxillin encodes a focal adhesion-associated protein and is involved in the
progression and aggressive phenotypes of malignancies through its interactions
with the actin cytoskeleton and key signal transduction oncogenes. The present
study aimed to investigate the clinicopathological and prognostic significance of
paxillin in gastric cancer. The expression of paxillin was evaluated using tissue
microarrays of gastric adjacent non-cancerous mucosa, adenoma and carcinoma
specimens by immunohistochemistry. Paxillin expression was compared against
clinicopathological parameters and the survival time of the patients. Paxillin
was highly expressed in gastric adenoma compared with that in non-neoplastic
mucosa and carcinoma (P<0.05). Paxillin expression was lower in the younger
carcinoma patients compared with that in the elder carcinoma patients (P<0.05).
Paxillin expression was negatively correlated with tumor size, depth of invasion
and lymph node metastasis, but not with patient gender, lymphatic or venous
invasion, or TNM staging (P>0.05). Higher paxillin expression was observed in
intestinal-type compared with diffuse-type carcinoma (P<0.05). Kaplan-Meier
analysis indicated a positive association between paxillin expression and
cumulative survival rate in all, advanced and intestinal-type carcinoma patients
(P<0.05). Multivariate analysis using the Cox proportional hazards model
indicated that patient age, depth of invasion, lymphatic invasion, lymph node
metastasis, TNM staging and Lauren classification were independent prognostic
factors for all gastric carcinomas (P<0.05). Aberrant paxillin expression may be
involved in the growth, invasion, metastasis and differentiation of gastric
carcinoma. Altered paxillin expression may, therefore, be employed as an
indicator of pathobiological behaviors and prognosis of gastric carcinomas.
PMID- 24348847
TI - Ultrasonography, X-ray and CT imaging findings of a giant pericardial lipoma:
Imaging diagnosis and review of the literature.
AB - Pericardial lipomas are rare and mostly asymptomatic tumors, which are usually
detected incidentally during physical examination. The present study describes a
case of giant pericardial lipoma that was diagnosed by surgical pathology. The
study also describe the X-ray, magnetic resonance imaging, and the distinguish of
the pericardial lipomas. The study also describes the ultrasonography, X-ray,
computed tomography and magnetic resonance imaging findings of the tumor, and a
review of the literature of cardiac lipoma, to help increase awareness of the
tumor and selection of the correct imaging method for diagnosis.
PMID- 24348848
TI - Primary yolk sac tumour of the urinary bladder: A case report and review of the
literature.
AB - We present a case of rare primary yolk sac tumour of the urinary bladder in
adulthood. A 31-year-old female patient presented with a history of chronic
ketamine abuse, which has not previously been shown to be associated with
malignancy development. The final diagnosis was established only after radical
cystectomy. A computed tomography (CT) scan showed paraaortic lymph node
metastasis. The patient was treated with systemic chemotherapy. A review of the
literature revealed that surgical excision and cisplatin-based chemotherapy
remain to be the standard of care for extragonadal yolk sac tumours.
PMID- 24348850
TI - Body mass index can affect gastrointestinal and genitourinary toxicity in
patients with prostate cancer treated with external beam radiation therapy.
AB - The aim of the present study was to determine the impact of obesity on radiation
induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54
patients with prostate cancer, treated with three-dimensional conformal radiation
therapy (RT), were reviewed. For each patient, the body mass index (BMI),
distance between the prostate and rectum (D) on a computerised tomography scan
and the dosimetric parameters of the rectum and bladder in the planning data of
RT, were analyzed. GI and GU toxicity was assessed during and following RT. The
results of the patients with a BMI of <25 (lower BMI) were compared with those of
the patients with a BMI of >=25 (higher BMI). The higher BMI group exhibited
significantly lower doses of V60 and V65 in the rectum than the lower BMI group.
No significant differences were found in D and bladder doses between the two
groups. The incidence of acute GI and GU toxicity and late GI and GU toxicity
were 41.7, 19.4, 35.3 and 5.7% in the lower BMI group, respectively, and 27.8,
27.8, 5.9 and 35.3% in the higher BMI group, respectively. In addition, a
significant difference was found in the incidence of late GU toxicity between the
two groups. Among patients who underwent RT for prostate cancer, those with
higher BMIs had a tendency to show lower incidences of GI toxicity and higher
incidences of GU toxicity than patients with lower BMIs. To conclude, an
increased effort must be made to reduce rectal doses in patients with lower BMIs.
Conversely, increased care for GU toxicity must be provided for overweight
patients.
PMID- 24348851
TI - Downregulation of ERK signaling impairs U2OS osteosarcoma cell migration in
collagen matrix by suppressing MMP9 production.
AB - The present study investigated the role of extracellular signal-regulated kinase
(ERK) activation in the migratory phenotype of human U2OS osteosarcoma (OS) cells
in a collagen matrix. The activation of ERK was inhibited by PD98059, a specific
inhibitor of ERK kinase. Additionally, no significant differences were observed
in the adhesion and proliferation of the cells with or without PD98059 treatment
in collagen-coated dishes. The migratory capacity of the U2OS cells was then
examined in non-coated and collagen-coated dishes, and the results depicted that
collagen I enhanced the migration of the U2OS cells, the effect of which was
significantly blocked by the treatment of the cells with PD98059. Furthermore,
enhanced gene and protein expression of matrix metalloproteinase 9 (MMP9), but
not MMP2, was observed to be involved in the enhanced migratory phenotype of the
U20S cells in the collagen-coated plates. This effect was partially abolished by
the treatment of the cells in the collagen-coated dishes with ERK inhibitor.
Collectively, the data demonstrate that ERK signaling is important for the
migration of U2OS cells through the extracellular matrix (ECM), which is
comprised mostly of collagen, by enhancing MMP9 production. These results may
contribute to the regulation of MMP9 production in metastatic OS.
PMID- 24348849
TI - Histone deacetylase inhibitor, valproic acid, radiosensitizes the C6 glioma cell
line in vitro.
AB - Valproic acid (VPA) is a well-tolerated drug that is used to treat seizure
disorders and that has recently been shown to inhibit histone deacetylase. The
present study investigated the effects of VPA on the radiosensitization of the
rat C6 glioma cell line in vitro. To select an appropriate treatment
concentration and time, MTT and flow cytometry assays were performed to measure
the inhibitory effects of VPA at various concentrations and incubation time
points. The radiosensitizing effect of VPA was determined using clonogenic
experiments. VPA- and radiation-induced C6 apoptosis was analyzed using
quantitative polymerase chain reaction and western blot analysis. Cell
proliferation was significantly inhibited by VPA in a time- and dose-dependent
manner (P<0.05). VPA enhanced radiation-induced C6 cell death and there was clear
inhibition of clonogenic formation [sensitizer enhancement ratio (SER), 1.30].
This effect was closely associated with the concentration of VPA. VPA treatment
decreased the mRNA and protein levels of Bcl-2, whereas increased changes were
detected with Bax. At a concentration of 0.5 mmol/l, VPA had a low toxicity and
enhanced the radiosensitization of the C6 cells. VPA may radiosensitize glioma
cells by inhibiting cellular proliferation and inducing apoptosis by regulating
apoptosis-related molecular changes.
PMID- 24348852
TI - Atypical imaging observations of branchial cleft cysts.
AB - The aim of the present study was to assess the atypical imaging manifestations of
branchial cleft cysts (BCCs) confirmed by pathology. Computerized tomography (CT)
or magnetic resonance imaging (MRI) of 17 BCC cases were reviewed. The imaging
features, including laterality, location, border, attenuation and internal
architecture, were evaluated. All 17 cases were second BCCs, including 5 cases of
Bailey type I classification cysts and 12 cases of type II classification cysts.
The atypical imaging features included signal and morphological abnormalities.
The abnormal signal intensities were caused by intracapsular bleeding (n=2) or
solidification of cystic fluid (n=2). Intracystic hemorrhaging revealed
homogeneous hyperintensity on T1-weighted image (T1WI) and T2-weighted image
(T2WI). Solidification of cystic fluid revealed slightly homogeneous
hyperintensity compared with muscle on T1WI and homogeneous hypointensity on T2WI
without enhancement. The aberrant morphology mainly presented as thickening of
the cystic wall (n=13). Thickened walls of BCCs with ill- (n=5) or well- (n=8)
defined borders were observed in 13 patients. In 3 patients, significant
enhancement was identified following intravenous gadolinium administration (n=4).
When with atypical CT or MRI features are presented, the typical location of BCCs
can help in the diagnosis, as it is located at the lateral portion of the neck
adjacent to the anterior border of the mandibular angle or sternocleidomastoid
muscle. The atypical observations, including variable signals, imply that the
cystic content has changed. Thickened walls indicate inflammation or cancerous
tendency and patients with ill-defined margins, vascular involvement or
lymphadenopathy atelectasis indicate malignant conversion.
PMID- 24348853
TI - First case report of an intracortical lipoma in an adult tibia.
AB - The current case report describes an adult male with an intracortical lipoma
accompanied by cystic changes in the tibial diaphysis. To the best of our
knowledge, intracortical lipoma in an adult tibia has not been previously
described. An anteroposterior radiograph of the tibia revealed an osteolytic
lesion on the diaphysis. Magnetic resonance imaging and computed tomography
revealed that the lesion was located in the cortex and consisted of fat and cyst
tissue. Surgical excision of the lesion confirmed diagnosis of an intracortical
lipoma.
PMID- 24348854
TI - Significance of thymidylate synthase expression for resistance to pemetrexed in
pulmonary adenocarcinoma.
AB - Pemetrexed (PEM), a multi-targeted antifolate, has promising clinical activity in
non-squamous non-small cell lung cancer. However, the majority of patients
eventually acquire resistance to PEM. To evaluate the resistant mechanisms, the
A549 lung adenocarcinoma cell line was exposed to stepwise increasing PEM
concentrations of 1.6, 6.4 and 16 MUM to establish three PEM-resistant lung
cancer cell lines, A549/PEM-1.6, -6.4 and -16. Growth inhibition was determined
by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay.
Expression of the genes encoding thymidylate synthase (TS), reduced folate
carrier (RFC) and folypoly-gamma-glutamate synthetase (FPGS) were analyzed by
quantitative real-time reverse transcription polymerase chain reaction. The three
A549 cell lines showed more resistance to PEM (3.7-, 17.3- and 38.0-fold,
respectively) compared with that of the parental cell line, which also showed
cross-resistance to cisplatin, but not to docetaxel, vinorelbine and 5
Fluorouracil (5-FU). TS gene expression was significantly increased in three PEM
resistant cells, relative to that of the parental cells, in a PEM dose-dependent
manner. Knockdown of TS expression with siRNA enhanced the cytotoxicity of PEM in
A549/PEM-16 cells. By contrast, the levels of RFC and FPGS gene expression in
A549/PEM-1.6 and -6.4 cells were significantly decreased, whereas the levels of
the two genes were restored in A549/PEM-16 cells. In summary, PEM-resistant A549
cells remained sensitive to docetaxel, vinorelbine and 5-FU. TS expression
appeared to be associated with resistance to PEM, which may be a predictive
marker for PEM sensitivity in lung adenocarcinoma.
PMID- 24348855
TI - Overexpression of Pygopus-2 is required for canonical Wnt activation in human
lung cancer.
AB - Lung cancer is the most common cause of cancer-related mortality worldwide. It is
necessary to improve the understanding of the molecular mechanisms involved in
lung cancer in order to develop more effective therapeutics for the treatment of
this fatal disease. The canonical Wnt signaling pathway has been known to be
important in a number of cancer types, including lung cancer. Pygopus (Pygo) is a
recently identified downstream component of the Wnt signaling pathway required
for beta-catenin/T-cell factor (TCF)-dependent transcription. However, the role
of Pygo in lung cancer remains to be elucidated. The present study showed that
Pygo2 is overexpressed in human lung cancer tissue samples and cell lines.
Expression levels of Pygo2 were found to correlate with cytosolic beta-catenin
protein levels in the samples examined. Co-immunofluorescent staining showed that
Pygo2 protein accumulated in the nuclei and colocalized with nuclear beta-catenin
in lung cancer cell lines expressing Pygo2. To investigate the functional
importance of the Pygo2 overexpression in lung cancer, short hairpin RNA (shRNA)
was used to knockdown Pygo2 mRNA in lung cancer cells expressing the gene. Pygo2
shRNA was observed to inhibit cell proliferation and decrease beta-catenin/TCF
dependent transcriptional activity in vitro. Furthermore, Pygo2 shRNA
significantly suppressed lung cancer xenograft models in vivo (P<0.05). These
results suggested that Pygo2 is a putative therapeutic target for human lung
cancer and overexpression of Pygo2 may be important for aberrant Wnt activation
in lung cancer.
PMID- 24348856
TI - hTERT promoter activity identifies osteosarcoma cells with increased EMT
characteristics.
AB - Epithelial-mesenchymal transition (EMT) is a critical step in order for
epithelial-derived malignancies to metastasize, however, its role in mesenchymal
derived tumors, i.e., osteosarcoma, remains unclear. Cancer stem cells (CSCs) are
enriched with cells that undergo EMT. The activity of telomerase is maintained in
normal stem cells and a number of malignant tumors. The current study observed
the heterogeneity of telomerase activity among individual osteosarcoma cells. We
hypothesized that telomerase-positive (TELpos) cells are enriched for stem cell
like and EMT properties. A human telomerase reverse transcriptase (hTERT)
promoter-reporter was applied to assess the telomerase activity of individual
MG63 osteosarcoma cells and sort them into TELpos and telomerase-negative
(TELneg) subpopulations. It was found that the TELpos cells exhibited an enhanced
ability to form sarcospheres in vitro. In addition, TELpos cells exhibited a
higher expression of vimentin, accompanied by an increased long/short axis ratio.
A panel of EMT-related genes was evaluated by quantitative PCR and western blot
analysis, and were found to be significantly upregulated in TELpos cells. Next,
the in vitro migration capacity was examined by Transwell assay, which confirmed
that TELpos cells are more prone to migration (2.6 fold). The results of the
present study support the concept that EMT also applies to mesenchymal-derived
osteosarcoma and draws a connection between telomerase and EMT characteristics.
PMID- 24348857
TI - Sarcomatoid (spindle cell) carcinoma of the pancreas: A case report and review of
the literature.
AB - Sarcomatoid (spindle cell) carcinoma of the pancreas is a rare, high-grade
epithelial malignancy composed predominantly or exclusively of spindle cells
demonstrating evidence of epithelial derivation, but no features indicative of a
specific line of mesenchymal differentiation. The current study presents the case
of an 85-year-old Caucasian male with a tumor mass in the body of the pancreas.
The individual subsequently underwent a distal pancreatectomy, splenectomy and
partial gastrectomy. Microscopic examination of the 3.3-cm mass located in the
body of the pancreas revealed a small, but high-grade, adenocarcinomatous
component that blended imperceptibly with malignant spindle cells. No light
microscopic or immunohistochemical evidence of specific mesenchymal
differentiation was identified, and the spindle cells, as in the case of the
carcinoma, were diffusely keratin-positive. Sarcomatoid (spindle cell) carcinoma
defined in this way rarely presents in the pancreas, with, to the best of our
knowledge, only six cases reported in the English literature.
PMID- 24348858
TI - Antitumor activities of Juemingzi (Cassia tora L.) on Balb/c sarcoma 180-injected
mice.
AB - The antitumor activity of Juemingzi (Cassia tora L.) was investigated in mice
that were fed various concentrations of the compound. Although mice fed a low
concentration (50 mg/kg b.w.) of Juemingzi exhibited a high tumor weight, the
higher feeding concentrations (100 and 200 mg/kg b.w.) were associated with lower
weight tumors. The growth rate of mouse splenocytes that were treated with 200
mg/kg b.w. Juemingzi was determined using a 3-(4,5-dimethyl-2-thiazolyl)-2,5
diphenyltetrazolium bromide assay. This rate of proliferation was higher than
that achieved with 100 and 50 mg/kg b.w. Juemingzi treatment by fetal bovine
serum, lipopolysaccharide or concanavalin A. Compared with the lower
concentrations of Juemingzi treatment, 200 mg/kg b.w. Juemingzi significantly
(P<0.05) reduced aspartate aminotransferase, alanine transaminase and blood urea
nitrogen levels. A high concentration of Juemingzi (200 mg/kg b.w.) significantly
(P<0.05) increased the levels of tumor necrosis factor-alpha and interleukin
1beta cytokines compared with those of the mice that were treated with 100 and 50
mg/kg b.w. Juemingzi.
PMID- 24348859
TI - Effect of epidermal growth factor receptor status on the outcomes of patients
with metastatic gastric cancer: A pilot study.
AB - The expression of epidermal growth factor receptor (EGFR) has been linked to
clinical outcome in several solid tumors. However, the clinical significance of
EGFR (c-erbB1) in gastric cancer remains unclear. The present study was designed
to detect the clinical implications of EGFR in the Turkish population. Paraffin
embedded tissue microarrays containing gastric cancer tissue were obtained from
30 patients. EGFR expression was detected using immunohistochemistry. The
correlation of this biomarker to the clinicopathological features and survival of
patients with gastric cancer was studied. The overall positivity rate of EGFR was
63.3%. EGFR expression was significantly correlated with an improved progression
free survival (PFS) and overall survival (OS) rate (P=0.039 and 0.01,
respectively). EGFR expression is a good prognostic marker for patients with
gastric cancer.
PMID- 24348860
TI - Safety and efficacy of radiation and chemoradiation in patients over 70 years old
with inoperable esophageal squamous cell carcinoma.
AB - The aim of the present study was to perform a retrospective analysis to
investigate the outcome and toxicity of radiation (RT) and chemoradiation (CRT)
in elderly, inoperable patients >70 years old. Between 2003 and 2012, 1,024
patients with squamous cell carcinoma (SCC) of the esophagus were treated at the
Department of Thoracic Cancer, West China Hospital (Chengdu, China). Of these
patients, 37 were >70 years old and had not undergone surgery, and were selected
for analysis. Of these 37 patients, CRT had been administered to 20 (54%).
Actuarial survival rates were determined by the Kaplan-Meier method. The one-year
survival rate in the CRT group (n=20) was 85%, while 35% of patients in the RT
group (n=17) survived for more than one year. The overall and progression-free
survival in the CRT group versus the RT group were 17 months [95% confidence
interval (CI), 11.861-22.139] versus eight months (95% CI, 6.674-9.326) (P=0.013)
and 14 months (95% CI, 9.617-18.383) versus five months (95% CI, 2.311-7.689)
(P=0.01), respectively. Patients irradiated with a dose of >50 Gy exhibited an
improved survival rate compared with patients who received a dose of <=50 Gy (18
vs. 14 months; P=0.049). Furthermore, patients with an Eastern Cooperative
Oncology Group (ECOG) score of <=1 had an improved prognosis compared with those
with an ECOG score of 2 (14 vs. seven months; P=0.006). The two regimens were
well-tolerated and there were no therapy-associated mortalities. The current
retrospective study indicated that patients of >70 years old with inoperable
esophageal SCC and a good ECOG score exhibit comparably better safety levels with
CRT and improved survival rates compared with RT alone.
PMID- 24348861
TI - A giant aneurysmal bone cyst of the rib: Case report.
AB - An aneurysmal bone cyst (ABC) is a benign tumor of the skeletal system, which
most frequently occurs in long bones. An ABC arising from the rib is extremely
rare and it is difficult to distinguish from other types of rib tumors. The
present study describes an unusual case of a large ABC in the rib of a 17-year
old male. The entity is discussed with particular emphasis on the
clinicopathological features, differential diagnosis and treatment. Due to
difficulties in the pre-operative diagnosis, a possible diagnosis of ABC should
be made aware when confronting an expansile rib mass. An en bloc resection of the
mass and the affected portion of the rib is mandatory to obtain a satisfactory
outcome.
PMID- 24348862
TI - microRNA-32 inhibits the proliferation and invasion of the SGC-7901 gastric
cancer cell line in vitro.
AB - microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs,
which suppress their target mRNAs at the post-transcriptional level. miRNAs play
key roles in tumor metastasis. The aim of the present study was to investigate
the expression of miRNA-32 (miR-32) on the biological behavior of the human
gastric cancer cell line, SGC-7901. SGC-7901 cells were transfected with miR-32
mimic, miR-32-inhibitor and empty plasmid vectors using LipofectamineTM 2000. The
expression of GFP was observed by fluorescent microscopy and miR-32 gene
expression was detected by quantitative polymerase chain reaction. The cell
counting kit-8 assay was performed to evaluate the effect of miR-32 expression on
cell proliferation in vitro. Alterations in the migration and metastatic
potential of SGC-7901 cells, prior to and following miR-32 gene transfection,
were assayed by cell chemotactic migration and invasion tests. The results of the
current study showed that the proliferation rate of the transfected SGC-7901
cells overexpressing miR-32 is reduced and cell chemotactic migration and
invasion potentials is markedly reduced following miR-32-mimic transfection
(P<0.05). In addition, the results demonstrated that overexpression of miR-32
greatly inhibits the proliferation and decreases the migration and invasion
capabilities of SGC-7901 cells in vitro.
PMID- 24348863
TI - Multiple microvenular hemangioma: A case report.
AB - The current study reports a case of multiple microvenular hemangioma (MH). A 35
year-old male presented with dark red maculopapules on the trunk and limbs that
had been apparent for 5 years. The number of lesions exceeded 100 in total. A
histological examination demonstrated multiple, irregular, branching venules in
the dermis, without any endothelial atypia. On immunohistochemical analysis of
the vascular structures, the endothelial cells stained positive for CD31, CD34
and factor VIII, and the perivascular cells stained positive for SMA and HHF-35.
These observations were consistent with a diagnosis of MH, and should be
differentiated from the most common differential diagnosis of patch-stage
Kaposi's sarcoma. There was no clear effect following topical application of
recombinant human interferon alpha-2b gel.
PMID- 24348864
TI - Prognostic role of BRCA1 mutation in patients with triple-negative breast cancer.
AB - Triple-negative breast cancer (TNBC) is proposed to be an immunohistochemical
surrogate of the basal-like breast cancer subtype. In spite of the relative
chemosensitivity of this cancer subtype, it is characterized by aggressive
clinical behavior; therefore, a further subclassification of TNBC is required to
develop new targeted treatment. In previous studies, a strong correlation between
BRCA1 mutation-associated tumors and TNBC has been identified. The aim of the
present study was to investigate the prognostic significance of carrying two
germline BRCA1 founder mutations (4153delA and 5382insC) in patients with TNBC in
the Latvian population. A total of 78 consecutive BRCA1 mutation-negative and 38
BRCA1 mutation-positive invasive TNBC patients in stage I-IV with no history of
ovarian or other primary advanced cancers, who had undergone definitive surgery
and genetic testing between 2005 and 2011, were deemed eligible for study.
Relapse rates and breast cancer-specific survival (BCS) outcomes were compared
between mutation carriers and non-carriers. Univariate and multivariate analyses
Cox proportional-hazards models were used to compute independent predictors of
survival outcomes. No statistically significant differences were identified in
relation to tumor size, T stage, stage, Ki-67 status and tumor differentiation
grade between the two groups. The median follow-up period was 36 months for
mutation carriers and 41 months for non-carriers. A higher proportion of BRCA1
mutation non-carriers experienced distant recurrence compared with that of
mutation carriers (P<0.03). BRCA1 mutation carriers had a significantly higher
BCS than non-carriers (94.9 vs. 76.9%; P<0.02). In the univariate analyses, BRCA1
positive status was associated with decreased risk of distant recurrence (HR,
0.228; 95% Cl, 0.052-0.997; P<0.049) and breast cancer-specific mortality (HR,
0.209; 95% Cl, 0.048-0.902; P<0.036). In the multivariate analysis Cox
proportional-hazards model, BRCA1-positive status was an independent favorable
prognostic factor for distant recurrence-free survival (HR, 3.301; 95% Cl, 1.102
9.893; P<0.033). In conclusion, results of the present study demonstrate that
positive BRCA1 founder mutation status in TNBC, with no evidence of ovarian or
other cancer type in advanced stage, significantly improves prognosis.
PMID- 24348865
TI - Renal myopericytoma: A case report with a literature review.
AB - Myopericytoma is a rare neoplasm that generally arises from the skin and
superficial soft tissues of distal extremities, and is particularly rare in the
visceral organs. The current report presents a case of giant myopericytoma
showing kidney involvement, which is extremely rare. A 39-year-old male presented
to the Department of Urology with a 2-month history of a painless and palpable
mass in the region of the left abdomen. Unenhanced computed tomography revealed a
9*10*18-cm3 mass that was heterogeneous with central lower density. The patient
underwent radical nephrectomy, including lymphadenectomy, without adjuvant
therapy. The tumor was composed of spindle-shaped myoid cells with a concentric
arrangement and showed immunoreactivity for smooth muscle actin and cluster of
differentiation (CD)10, and had a Ki-67 index of <1%; however, staining was
negative for CD34, desmin, S-100 protein, cytokeratin, human melanoma black (HMB)
45, B-cell lymphoma (Bcl)-2 and CD99. Routine follow-up revealed no local or
distant metastatic signs of reccurrence for 20 months. The present report shows
that renal myopericytoma may be a benign tumor, and surgical excision without
adjuvant therapy may be the only potentially curative treatment approach.
PMID- 24348866
TI - Computed tomography-guided core needle biopsy of lung lesions: Diagnostic yield
and correlation between factors and complications.
AB - The aim of the present study was to determine the diagnostic accuracy of computed
tomography (CT)-guided core needle biopsy (CNB) and to retrospectively analyze
the correlation between the factors and complications of the procedure. Between
January 2009 and June 2010, CNB was performed on 345 lung lesions in 343
patients. These patients were then followed up for at least two years. The
sensitivity, specificity, accuracy, positive predictive value (PPV) and negative
predictive value (NPV) of the CNB diagnoses were calculated. The correlation
between factors, such as smoking, positoin and maximal diameter, and the
complications of pneumothorax and hemorrhage was analyzed by chi2 test. The
sensitivity, specificity, accuracy, PPV and NPV of the CNB diagnoses were 97.3,
100, 97.7, 100 and 87.7%, respectively. A statistically significant correlation
was found between pneumothorax and the factors of smoking (P=0.015) and position
(P<0.01) and length of the needle in the normal parenchyma (P=0.011), as well as
between hemorrhage and the maximal diameter (P=0.005) and length of the needle in
the normal parenchyma (P<0.01) and the frequency of needle adjustments (P<0.01).
A CT-guided core needle biopsy of the lung lesions provides a high diagnostic
yield. Smoking, the decubitus position and a longer length of the needle in the
normal parenchyma were found to represent risk factors for a pneumothorax. In
addition, a small diameter and longer length of the needle in the normal
parenchyma and a more frequent adjustment of the needle were poor predictive
factors of hemorrhage.
PMID- 24348867
TI - Polydatin inhibits growth of lung cancer cells by inducing apoptosis and causing
cell cycle arrest.
AB - Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number
of biological functions. However, the anticancer activity of PD has been poorly
investigated. In the present study, thiazolyl blue tetrazolium bromide assay was
used to evaluate the inhibitory effect of PD on cell growth. Cell cycle
distribution and apoptosis were investigated by flow cytometry. In addition, the
expression of several proteins associated with apoptosis and cell cycle were
analyzed by western blot analysis. The results demonstrated that PD significantly
inhibits the proliferation of A549 and NCI-H1975 lung cancer cell lines and
causes dose-dependent apoptosis. Cell cycle analysis revealed that PD induces S
phase cell cycle arrest. Western blot analysis showed that the expression of Bcl
2 decreased as that of Bax increased, and the expression of cyclin D1 was also
suppressed. The results suggest that PD has potential therapeutic applications in
the treatment of lung cancer.
PMID- 24348869
TI - Predicting ICU admissions from attempted suicide presentations at an Emergency
Department in Central Queensland.
AB - BACKGROUND: Emergency medicine physicians and psychiatric staff face a
challenging job in risk stratifying patients presenting with suicide attempts to
predict which patients need intensive care unit admission, hospital admission or
can be discharged with psychiatry follow up. AIMS: This study aims to analyse
patients who were admitted to the intensive care unit or regular ward for suicide
attempt, and the methods they employed in a rural Australian base hospital.
METHOD: We conducted a retrospective analysis of patients who presented with
suicide attempts to the Rockhampton Base Hospital Emergency Department,
Queensland Australia from 1 September 2007 to 31 August 2009. Multivariate
logistic regression was undertaken to identify risk factors for ICU and regular
ward admission, and predictors of suicide method. RESULTS: There were 570
patients presenting with suicide attempts, 74 of which were repeat suicide
attempts. There was a 10- fold increase in the odds of intensive care unit or ICU
admission (CI 1.45-81.9, p=0.02) for patients who presented with drug overdose.
Increased age (OR=1.02, 95 per cent CI 1.00-1.03, p=0.05), drug overdose
(OR=2.69, 95 per cent CI 1.37-5.29, p=0.004), and previous suicide attempt
(OR=1.53, 95 per cent CI 1.03-2.28, p=0.03) were significantly correlated with
hospital admission. Male patients (OR=2.76, 95 per cent CI 1.43-5.30, p=0.002)
and Aboriginal patients (OR=3.38, 95 per cent CI 1.42-8.05, p=0.006) were more
likely to choose hanging as a suicide method. CONCLUSION: We identified drug
overdose as a strong predictor of ICU admission, while age, drug overdose and
history of previous suicide attempts predict hospital admission. We recommend
reviewing physician practices, especially safe medication, in suicide risk
patients. Our study also highlights the need for continued close collaboration by
acute care and community mental health providers for quality improvement.
PMID- 24348868
TI - MAGNETIC NANOPARTICLE HYPERTHERMIA IN CANCER TREATMENT.
AB - The activation of magnetic nanoparticles (mNPs) by an alternating magnetic field
(AMF) is currently being explored as technique for targeted therapeutic heating
of tumors. Various types of superparamagnetic and ferromagnetic particles, with
different coatings and targeting agents, allow for tumor site and type
specificity. Magnetic nanoparticle hyperthermia is also being studied as an
adjuvant to conventional chemotherapy and radiation therapy. This review provides
an introduction to some of the relevant biology and materials science involved in
the technical development and current and future use of mNP hyperthermia as
clinical cancer therapy.
PMID- 24348870
TI - Why are organisations that provide healthcare services fuzzy?
AB - BACKGROUND: Healthcare organisations are an enigma to many people inand outside
the service. Organisational fuzziness is a common state, characterised by a lack
of clarity, lack of awareness, lack of organisational knowledge, and the reliance
on practice and custom instead of transparency. AIMS: The objective of this study
was to obtain a better understanding of what causes this fuzziness and provide an
actionable description of fuzzy organisations. Such a description is essential to
managing and preventing organisational fuzziness. METHOD: We used a longitudinal
case study in an integrated healthand social care organisation to obtain a
thorough understanding of how the organisation functions. These indepth insights
allowed the identification of three generators of fuzziness. RESULTS: We found
that the three main generators of organisational fuzziness are change, informal
organisation and complexity. Organisational fuzziness is thus partly due to the
inherent complexities of human systems. However, also continuous change and the
inability of the system to adapt its formal structures resulted in structures
deteriorating or no longer being appropriate. CONCLUSION: Existing approaches to
explain unclear or absent structures in healthcare organisations by describing
these organisations as complex adaptive systems (CAS) are too simplistic. While
aspects relating to people and their interactions are indeed complex, fuzziness
of structural aspects are often the result of continuous change and insufficient
organisational capacity to adapt to it.
PMID- 24348871
TI - Why drug shortages are an ethical issue.
AB - Drug shortages are a growing problem in developed countries. To some extent they
are the result of technical and organisational failures, but to view drug
shortages simply as technical and economic phenomena is to miss the fact that
they are also ethical and political issues. This observation is important because
it highlights both the moral and political imperative to respond to drug
shortages as vigorously as possible, and the need for those addressing shortages
to do so in ethically and politically sophisticated ways. This brief article
outlines the ethical issues that need to be considered by anyone attempting to
understand or address drug shortages.
PMID- 24348872
TI - Clinical profile and visual outcome of ocular injuries in a rural area of western
India.
AB - BACKGROUND: Ocular trauma is a major cause of visual impairment and morbidity
worldwide. AIMS: To identify the various type of ocular injury in a rural area,
determine the presence of any associated visual damage and assess the final
visual outcome after treatment. METHOD: Hospital-based, prospective study
conducted over a period of two years. A total of 60 patients of ocular trauma
were included. RESULTS: Ocular injuries were more commonly seen in adult (55 per
cent) patients who were associated with agricultural work (43.33 per cent). They
were more common in male patients (71.67 per cent). Closed globe injury (68.33
per cent) was more common than open globe injury (31.67 per cent). Both in open
and closed globe injuries, the commonest object causing injury was a wooden
stick. Just 26.7 per cent of the patients had a visual acuity better than 6/60 at
presentation; while after completed treatment at two months follow-up, 68.3 per
cent had best corrected visual acuity better than 6/60. CONCLUSION: Agricultural
trauma is an important cause of monocular blindness in rural India. The visual
outcome depends upon the site and size of the injury and the extent of the ocular
damage.
PMID- 24348873
TI - Enablers of and barriers to making healthy change during pregnancy in overweight
and obese women.
AB - BACKGROUND: High Body Mass Index (BMI) during pregnancy is associated with an
increased risk of adverse health outcomes. Making healthy change during pregnancy
is beneficial, especially for overweight and obese women. AIMS: The aim of this
study was to explore the barriers and enablers identified by overweight and obese
women that preclude and facilitate making healthy change during pregnancy.
METHOD: Twenty-six women who were overweight or obese during pregnancy were
interviewed at 28 weeks gestational age. Interviews were transcribed verbatim and
the analysis is based on the thematic analysis methodology. RESULTS: The core
concept of "being pregnant" indicated women consider this specific time as both a
reason not to make healthy change as well as a motivation for change. Overweight
and obese women cited the following barriers to making healthy change during
pregnancy: physiological (e.g. pregnancy complications and tiredness); emotional
(e.g. preference and mood); cognitive (e.g. lack knowledge); interpersonal (e.g.
lack support); and environmental (e.g. availability of healthy choice). Similar
enablers were identified by overweight and obese women: physiological (e.g.
relief of pregnancy symptoms); emotional (e.g. approval and commitment);
cognitive (e.g. knowledge and belief); interpersonal (e.g. family support); and
environmental (e.g. help from others). More barriers than enablers were given,
indicating that women were more sensitive to barriers than the enablers for
making healthy change. Factors viewed by some women as barriers were viewed as
enablers by others. CONCLUSION: When designing interventions to promote healthy
eating and physical activity during pregnancy, individually focused interventions
must be implemented in conjunction with environmental-level interventions to
facilitate behaviour change.
PMID- 24348875
TI - Lipid-dependent and -independent regulation of nuclear envelope disassembly.
PMID- 24348876
TI - JOCB Bulletin.
PMID- 24348874
TI - Recent progress in tissue optical clearing.
AB - Tissue optical clearing technique provides a prospective solution for the
application of advanced optical methods in life sciences. This paper gives a
review of recent developments in tissue optical clearing techniques. The
physical, molecular and physiological mechanisms of tissue optical clearing are
overviewed and discussed. Various methods for enhancing penetration of optical
clearing agents into tissue, such as physical methods, chemical-penetration
enhancers and combination of physical and chemical methods are introduced.
Combining the tissue optical clearing technique with advanced microscopy image or
labeling technique, applications for 3D microstructure of whole tissues such as
brain and central nervous system with unprecedented resolution are demonstrated.
Moreover, the difference in diffusion and/or clearing ability of selected agents
in healthy versus pathological tissues can provide a highly sensitive indicator
of the tissue health/pathology condition. Finally, recent advances in optical
clearing of soft or hard tissue for in vivo imaging and phototherapy are
introduced. [Formula: see text].
PMID- 24348877
TI - Substrate Stiffness Regulates PDGF-Induced Circular Dorsal Ruffle Formation
Through MLCK.
AB - As atherosclerosis progresses, vascular smooth muscle cells (VSMCs) invade from
the medial layer into the intimal layer and proliferate, contributing to
atherosclerotic plaque formation. This migration is stimulated in part by
platelet-derived growth factor (PDGF), which is released by endothelial cells and
inflammatory cells, and vessel stiffening, which occurs with age and
atherosclerosis progression. PDGF induces the formation of circular dorsal
ruffles (CDRs), actin-based structures associated with increased cell motility.
Here we show that mechanical changes in matrix stiffness enhance the formation of
CDRs in VSMCs in response to PDGF stimulation. Our data indicate that matrix
stiffness increases cellular contractility, and that intracellular pre-stress is
necessary for robust CDR formation. When treated with agonists that promote
contractility, cells increase CDR formation, whereas agonists that inhibit
contractility lead to decreased CDR formation. Substrate stiffness promotes CDR
formation in response to PDGF by upregulating Src activity through myosin light
chain kinase. Together, these data indicate that vessel stiffening accompanying
atherogenesis may exacerbate VSMC response to PDGF leading to CDR formation.
PMID- 24348879
TI - Improved Convolutive and Under-Determined Blind Audio Source Separation with MRF
Smoothing.
AB - Convolutive and under-determined blind audio source separation from noisy
recordings is a challenging problem. Several computational strategies have been
proposed to address this problem. This study is concerned with several
modifications to the expectation-minimization-based algorithm, which iteratively
estimates the mixing and source parameters. This strategy assumes that any entry
in each source spectrogram is modeled using superimposed Gaussian components,
which are mutually and individually independent across frequency and time bins.
In our approach, we resolve this issue by considering a locally smooth temporal
and frequency structure in the power source spectrograms. Local smoothness is
enforced by incorporating a Gibbs prior in the complete data likelihood function,
which models the interactions between neighboring spectrogram bins using a Markov
random field. Simulations using audio files derived from stereo audio source
separation evaluation campaign 2008 demonstrate high efficiency with the proposed
improvement.
PMID- 24348878
TI - Analytic study of three-dimensional single cell migration with and without
proteolytic enzymes.
AB - Cell motility is a fundamental physiological process that regulates cellular fate
in healthy and diseased systems. Cells cultured in 3D environments often exhibit
biphasic dependence of migration speed with cell adhesion. Much is not understood
about this very common behavior. A phenomenological model for 3D single-cell
migration that exhibits biphasic behavior and highlights the important role of
steric hindrance is developed and studied analytically. Changes in the biphasic
behavior in the presence of proteolytic enzymes are investigated. Our methods
produce a framework to determine analytic formulae for the mean cell speed,
allowing general statements in terms of parameters to be explored, which will be
useful when interpreting future experimental results. Our formula for mean cell
speed as a function of ligand concentration generalizes and extends previous
computational models that have shown good agreement with in vitro experiments.
PMID- 24348880
TI - Network Based Prediction Model for Genomics Data Analysis.
AB - Biological networks, such as genetic regulatory networks and protein interaction
networks, provide important information for studying gene/protein activities. In
this paper, we propose a new method, NetBoosting, for incorporating a priori
biological network information in analyzing high dimensional genomics data.
Specially, we are interested in constructing prediction models for disease
phenotypes of interest based on genomics data, and at the same time identifying
disease susceptible genes. We employ the gradient descent boosting procedure to
build an additive tree model and propose a new algorithm to utilize the network
structure in fitting small tree weak learners. We illustrate by simulation
studies and a real data example that, by making use of the network information,
NetBoosting outperforms a few existing methods in terms of accuracy of prediction
and variable selection.
PMID- 24348881
TI - Comparative Study of Continuous and Pulsatile Left Ventricular Assist Devices on
Hemodynamics of a Pediatric End-to-Side Anastomotic Graft.
AB - Although there are many studies that focus on understanding the consequence of
pumping mode (continuous vs. pulsatile) associated with ventricular assist
devices (VADs) on pediatric vascular pulsatility, the impact on local
hemodynamics has been largely ignored. Hence, we compare not only the hemodynamic
parameters indicative of pulsatility but also the local flow fields in the aorta
and the great vessels originating from the aortic arch. A physiologic graft
anastomotic model is constructed based on a pediatric, patient specific, aorta
with a graft attached on the ascending aorta. The flow is simulated using a
previously validated second-order accurate Navier-Stokes flow solver based upon a
finite volume approach. The major findings are: (1) pulsatile support provides a
greater degree of vascular pulsatility when compared to continuous support,
which, however, is still 20% less than pulsatility in the healthy aorta; (2)
pulsatile support increases the flow in the great vessels, while continuous
support decreases it; (3) complete VAD support results in turbulence in the
aorta, with maximum principal Reynolds stresses for pulsatile support and
continuous support of 7081 and 249 dyn/cm2, respectively; (4) complete pulsatile
support results in a significant increase in predicted hemolysis in the aorta;
and (5) pulsatile support causes both higher time-averaged wall shear stresses
(WSS) and oscillatory shear indices (OSI) in the aorta than does continuous
support. These findings will help to identify the risk of graft failure for
pediatric patients with pulsatile and continuous VADs.
PMID- 24348882
TI - The effect of grid resolution on estimates of the burden of ozone and fine
particulate matter on premature mortality in the United States.
AB - Assessments of human health impacts associated with outdoor air pollution often
use air quality models to represent exposure, but involve uncertainties due to
coarse model resolution. Here we quantify how estimates of mortality in the
United States attributable to ozone (O3) and fine particulate matter (PM2.5) at
coarse resolution differ from those at finer resolution. Using the finest modeled
concentrations (12 km), we estimate that 66,000 (95% CI, 39,300 - 84,500) all
cause and 21,400 (5,600 - 34,200) respiratory deaths per year are attributable to
PM2.5 and O3 concentrations above low-concentration thresholds, respectively.
Using model results at 36 km resolution gives mortality burdens that are 11%
higher for PM2.5 and 12% higher for O3 than the 12 km estimates, suggesting a
modest positive bias. We also scale modeled concentrations at 12 km to coarser
resolutions by simple averaging, and repeat the mortality assessment at multiple
resolutions from 24 to 408 km, including the resolutions of global models; in
doing so, we account for the effect of resolution on population exposure. Coarse
grid resolutions produce mortality estimates that are substantially biased low
for PM2.5 (30-40% lower than the 12 km estimate at >250 km resolution), but less
than 6% higher for O3 at any resolution. Mortality estimates for primary PM2.5
species show greater bias at coarse resolution than secondary species. These
results suggest that coarse resolution global models (>100 km) are likely biased
low for PM2.5 health effects. For ozone, biases due to coarse resolution may be
much smaller, and the effect on modeled chemistry likely dominates.
PMID- 24348883
TI - The speakers' bureau system: a form of peer selling.
AB - In the speakers' bureau system, physicians are recruited and trained by
pharmaceutical, biotechnology, and medical device companies to deliver
information about products to other physicians, in exchange for a fee. Using
publicly available disclosures, we assessed the thesis that speakers' bureau
involvement is not a feature of academic medicine in Canada, by estimating the
prevalence of participation in speakers' bureaus among Canadian faculty in one
medical specialty, cardiology. We analyzed the relevant features of an actual
contract made public by the physician addressee and applied the Canadian Medical
Association (CMA) guidelines on physician-industry relations to participation in
a speakers' bureau. We argue that speakers' bureau participation constitutes a
form of peer selling that should be understood to contravene the prohibition on
product endorsement in the CMA Code of Ethics. Academic medical institutions, in
conjunction with regulatory colleges, should continue and strengthen their
policies to address participation in speakers' bureaus.
PMID- 24348884
TI - Multispecialty physician networks in Ontario.
AB - BACKGROUND: Large multispecialty physician group practices, with a central role
for primary care practitioners, have been shown to achieve high-quality, low-cost
care for patients with chronic disease. We assessed the extent to which informal
multispecialty physician networks in Ontario could be identified by using health
administrative data to exploit natural linkages among patients, physicians, and
hospitals based on existing patient flow. METHODS: We linked each Ontario
resident to his or her usual provider of primary care over the period from fiscal
year 2008/2009 to fiscal year 2010/2011. We linked each specialist to the
hospital where he or she performed the most inpatient services. We linked each
primary care physician to the hospital where most of his or her ambulatory
patients were admitted for non-maternal medical care. Each resident was then
linked to the same hospital as his or her usual provider of primary care. We
computed "loyalty" as the proportion of care to network residents provided by
physicians and hospitals within their network. Smaller clusters were aggregated
to create networks based on a minimum population size, distance, and loyalty.
Networks were not constrained geographically. RESULTS: We identified 78
multispecialty physician networks, comprising 12,410 primary care physicians,
14,687 specialists, and 175 acute care hospitals serving a total of 12,917,178
people. Median network size was 134,723 residents, 125 primary care physicians,
and 143 specialists. Virtually all eligible residents were linked to a usual
provider of primary care and to a network. Most specialists (93.5%) and primary
care physicians (98.2%) were linked to a hospital. Median network physician
loyalty was 68.4% for all physician visits and 81.1% for primary care visits.
Median non-maternal admission loyalty was 67.4%. Urban networks had lower
loyalties and were less self-contained but had more health care resources.
INTERPRETATION: We demonstrated the feasibility of identifying informal
multispecialty physician networks in Ontario on the basis of patterns of health
care-seeking behaviour. Networks were reasonably self-contained, in that
individual residents received most of their care from providers within their
respective networks. Formal constitution of networks could foster accountability
for efficient, integrated care through care management tools and quality
improvement, the ideas behind "accountable care organizations."
PMID- 24348886
TI - Herpes zoster as a marker of underlying malignancy.
AB - BACKGROUND: Both herpes zoster and malignancy are associated with
immunosuppression. However, the association between herpes zoster and the
subsequent diagnosis of malignancy is unclear. We undertook this study to assess
whether a diagnosis of herpes zoster is a risk factor for subsequent malignancy.
METHODS: For this matched retrospective cohort study, a physician billing
database was used to identify individuals 18 years of age or older with a
diagnosis of herpes zoster and no prior diagnosis of cancer or HIV infection.
Individuals with a herpes zoster diagnosis were matched one-to-one to individuals
without a herpes zoster diagnosis, and both groups were examined for up to 5
years for diagnosis of cancer. RESULTS: A total of 542,575 individuals with a
diagnosis of herpes zoster were identified. Compared with matched controls, these
patients were more likely (p < 0.001) to have a history of myocardial infarction,
asthma, congestive heart failure, chronic obstructive pulmonary disease, diabetes
mellitus, and hypertension. The incidence of cancer was significantly greater
among individuals with herpes zoster than among those without herpes zoster, for
both men and women and across all time intervals studied (up to 5 years). The
greatest adjusted hazard ratio was seen 180 days after a herpes zoster diagnosis
(1.19, 95% confidence interval 1.12-1.25); the hazard ratio decreased as the time
from herpes zoster diagnosis increased. Lymphoma was the type of cancer with the
greatest relative increase in incidence following diagnosis of herpes zoster.
INTERPRETATION: There is a risk of malignancy following an episode of herpes
zoster in both men and women and in all age groups 18 years and over. The risk is
greatest during the first 180 days following the diagnosis of herpes zoster.
PMID- 24348885
TI - Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium
difficile infection among hospitalized patients: systematic review and meta
analysis.
AB - BACKGROUND: Antibiotic-associated diarrhea (AAD) and Clostridium difficile
infection (CDI) are associated with high morbidity, mortality, and health care
costs. Probiotics may mitigate the existing disease burden. We performed a
systematic review and meta-analysis to evaluate the efficacy of co-administration
of probiotics with antibiotics in preventing these adverse outcomes in adult
inpatients. METHODS: Systematic searches of MEDLINE (1946 to May 2012), Embase
(1980 to May 2012), and the Cochrane Central Register of Controlled Trials were
undertaken on May 31, 2012, to identify relevant publications. We searched for
randomized controlled trials, published in English, of adult inpatients who were
receiving antibiotics and who were randomly assigned to co-administration of
probiotics or usual care, with or without the use of placebo. Studies were
included if they reported on AAD or CDI (or both) as outcomes. Data for
predetermined criteria evaluating study characteristics, methods, and risk of
bias were extracted. Trials were given a global rating of good, fair, or poor by
at least 2 reviewers. Meta-analyses were performed using a random-effects model,
and pooled relative risks (RRs) and 95% confidence intervals (CIs) were
calculated. RESULTS: Sixteen trials met the criteria for inclusion in this
review. Four studies were of good quality, 5 were of fair quality, and 7 were of
poor quality. Pooled analyses revealed significant reductions in the risks of AAD
(RR 0.61, 95% CI 0.47 to 0.79) and CDI (RR 0.37, 95% CI 0.22 to 0.61) among
patients randomly assigned to co-administration of probiotics. The number needed
to treat for benefit was 11 (95% CI 8 to 20) for AAD and 14 (95% CI 9 to 50) for
CDI. With subgroup analysis, significant reductions in rates of both AAD and CDI
were retained in the subgroups of good-quality trials, the trials assessing a
primarily Lactobacillus-based probiotic formulation, and the trials for which the
follow-up period was less than 4 weeks. INTERPRETATION: Probiotics used
concurrently with antibiotics reduce the risk of AAD and CDI.
PMID- 24348887
TI - Severe Hypoxia: Consequences to Neural Stem Cells and Neurons.
AB - BACKGROUND: Multiple neurological diseases result from a pathological hypoxia in
the brain, resulting in various motor, sensory or cognitive sequelae.
Understanding the response of neural stem cells (NSCs) and differentiated neurons
to hypoxia will help better treat such diseases. METHODS: We exposed mouse
embryonic primary neurons (PN) and neural stem cells to 1% O2 in vitro. RESULTS:
Both cell types survived and retained their immunocyto-chemical markers, and
neurons showed no obvious morphological changes. Microarray analysis showed that
the number of genes with significantly altered expression levels was almost five
fold higher in NSCs compared to PN. NSCs displayed a clear block in G1/S phase of
the cell cycle and a number of down-regulated cytokine genes. Various growth
factors (e.g. neural growth factor, prolactin), involved in survival and
proliferation, genes of the Notch pathway, and genes involved in glial
differentiation, and cell-matrix adhesion were up-regulated. PN displayed a down
regulation of a number of genes involved in neuron-specific functions, in
particular, transmitter-related (e.g. synaptic transmission, neurotransmitter
transport and release, learning, adult behavior). CONCLUSIONS: We conclude that
hypoxia 1-down-regulates genes involved in multiple neuronal functions which can
negatively impact learning and memory; 2-induces a cell cycle block in NSCs; 3
can precondition NSC towards a particular differentiation potential while
maintaining them fully undifferentiated.
PMID- 24348888
TI - PAX3-FKHR regulates the expression of pleiotrophin to mediate motility in
alveolar rhabdomyosarcoma cells.
AB - More than 80% of the aggressive alveolar rhabdomyosarcoma (ARMSs) harbor a PAX3
FKHR fusion transcription factor, which regulates cell motility and promotes
metastasis. Our hypothesis is that PAX3-FKHR regulates cell motility by
regulating the expression of its transcriptional targets that are also its
downstream effectors, which if identified, may lead to novel therapeutic
approaches for treating ARMS. Here we report that PAX3-FKHR regulates the
expression of pleiotrophin (PTN) by binding specifically to a paired-box domain
binding-site in the PTN promoter, indicating that PTN is a transcriptional target
of PAX3-FKHR. Significantly, we show that PTN regulates ARMS cell motility. Taken
together, we have identified PTN as a novel transcriptional target of PAX3-FKHR
that promotes ARMS cell motility. PTN may be a novel therapeutic target for the
treatment of ARMS.
PMID- 24348889
TI - Light-addressable measurements of cellular oxygen consumption rates in microwell
arrays based on phase-based phosphorescence lifetime detection.
AB - A digital light modulation system that utilizes a modified commercial digital
micromirror device (DMD) projector, which is equipped with a UV light-emitting
diode as a light modulation source, has been developed to spatially direct
excited light toward a microwell array device to detect the oxygen consumption
rate (OCR) of single cells via phase-based phosphorescence lifetime detection.
The microwell array device is composed of a combination of two components: an
array of glass microwells containing Pt(II) octaethylporphine (PtOEP) as the
oxygen-sensitive luminescent layer and a microfluidic module with pneumatically
actuated glass lids set above the microwells to controllably seal the microwells
of interest. By controlling the illumination pattern on the DMD, the modulated
excitation light can be spatially projected to only excite the sealed microwell
for cellular OCR measurements. The OCR of baby hamster kidney-21 fibroblast cells
cultivated on the PtOEP layer within a sealed microwell has been successfully
measured at 104 +/- 2.96 amol s(-1) cell(-1). Repeatable and consistent
measurements indicate that the oxygen measurements did not adversely affect the
physiological state of the measured cells. The OCR of the cells exhibited a good
linear relationship with the diameter of the microwells, ranging from 400 to 1000
MUm and containing approximately 480 to 1200 cells within a microwell. In
addition, the OCR variation of single cells in situ infected by Dengue virus with
a different multiplicity of infection was also successfully measured in real
time. This proposed platform provides the potential for a wide range of
biological applications in cell-based biosensing, toxicology, and drug discovery.
PMID- 24348890
TI - Analysis of a laminar-flow diffusional mixer for directed self-assembly of
liposomes.
AB - The present work describes the operation and simulation of a microfluidic laminar
flow mixer. Diffusive mixing takes place between a core solution containing
lipids in ethanol and a sheath solution containing aqueous buffer, leading to
self assembly of liposomes. Present device architecture hydrodynamically focuses
the lipid solution into a cylindrical core positioned at the center of a
microfluidic channel of 125 * 125-MUm(2) cross-section. Use of the device
produces liposomes in the size range of 100-300 nm, with larger liposomes forming
at greater ionic strength in the sheath solution and at lower lipid concentration
in the core solution. Finite element simulations compute the concentration
distributions of solutes at axial distances of greater than 100 channel widths.
These simulations reduce computation time and enable computation at long axial
distances by utilizing long hexahedral elements in the axial flow region and fine
tetrahedral elements in the hydrodynamic focusing region. Present meshing
technique is generally useful for simulation of long microfluidic channels and is
fully implementable using comsol Multiphysics. Confocal microscopy provides
experimental validation of the simulations using fluorescent solutions containing
fluorescein or enhanced green fluorescent protein.
PMID- 24348891
TI - Cylindrical glass nanocapillaries patterned via coarse lithography (>1 MUm) for
biomicrofluidic applications.
AB - We demonstrate a new method of fabricating in-plane cylindrical glass
nanocapillaries (<100 nm) that does not require advanced patterning techniques
but the standard coarse photolithography (>1 MUm). These nanocapillaries are self
enclosed optically transparent and highly regular over large areas. Our method
involves structuring MUm-scale rectangular trenches in silicon, sealing the
trenches into enclosed triangular channels by depositing phosphosilicate glass,
and then transforming the channels into cylindrical capillaries through shape
transformation by the reflow of annealed glass layer. Extended anneal has the
structures shrunk into nanocapillaries preserving their cylindrical shape.
Nanocapillaries ~50 nm in diameter and effective stretching of digested lambda
phage DNA in them are demonstrated.
PMID- 24348892
TI - Erratum: "Electro-entropic excluded volume effects on DNA looping and relaxation
in nanochannels" [Biomicrofluidics 7, 054119 (2013)].
AB - [This corrects the article on p. 054119 in vol. 7.].
PMID- 24348893
TI - Penalized Regression and Risk Prediction in Genome-Wide Association Studies.
AB - An important task in personalized medicine is to predict disease risk based on a
person's genome, e.g. on a large number of single-nucleotide polymorphisms
(SNPs). Genome-wide association studies (GWAS) make SNP and phenotype data
available to researchers. A critical question for researchers is how to best
predict disease risk. Penalized regression equipped with variable selection, such
as LASSO and SCAD, is deemed to be promising in this setting. However, the
sparsity assumption taken by the LASSO, SCAD and many other penalized regression
techniques may not be applicable here: it is now hypothesized that many common
diseases are associated with many SNPs with small to moderate effects. In this
article, we use the GWAS data from the Wellcome Trust Case Control Consortium
(WTCCC) to investigate the performance of various unpenalized and penalized
regression approaches under true sparse or non-sparse models. We find that in
general penalized regression outperformed unpenalized regression; SCAD, TLP and
LASSO performed best for sparse models, while elastic net regression was the
winner, followed by ridge, TLP and LASSO, for non-sparse models.
PMID- 24348896
TI - March of the titans: the locomotor capabilities of sauropod dinosaurs.
PMID- 24348895
TI - DNA barcoding the Canadian Arctic flora: core plastid barcodes (rbcL + matK) for
490 vascular plant species.
AB - Accurate identification of Arctic plant species is critical for understanding
potential climate-induced changes in their diversity and distributions. To
facilitate rapid identification we generated DNA barcodes for the core plastid
barcode loci (rbcL and matK) for 490 vascular plant species, representing nearly
half of the Canadian Arctic flora and 93% of the flora of the Canadian Arctic
Archipelago. Sequence recovery was higher for rbcL than matK (93% and 81%), and
rbcL was easier to recover than matK from herbarium specimens (92% and 77%).
Distance-based and sequence-similarity analyses of combined rbcL + matK data
discriminate 97% of genera, 56% of species, and 7% of infraspecific taxa. There
is a significant negative correlation between the number of species sampled per
genus and the percent species resolution per genus. We characterize barcode
variation in detail in the ten largest genera sampled (Carex, Draba, Festuca,
Pedicularis, Poa, Potentilla, Puccinellia, Ranunculus, Salix, and Saxifraga) in
the context of their phylogenetic relationships and taxonomy. Discrimination with
the core barcode loci in these genera ranges from 0% in Salix to 85% in Carex.
Haplotype variation in multiple genera does not correspond to species boundaries,
including Taraxacum, in which the distribution of plastid haplotypes among Arctic
species is consistent with plastid variation documented in non-Arctic species.
Introgression of Poa glauca plastid DNA into multiple individuals of P. hartzii
is problematic for identification of these species with DNA barcodes. Of three
supplementary barcode loci (psbA-trnH, psbK-psbI, atpF-atpH) collected for a
subset of Poa and Puccinellia species, only atpF-atpH improved discrimination in
Puccinellia, compared with rbcL and matK. Variation in matK in Vaccinium
uliginosum and rbcL in Saxifraga oppositifolia corresponds to variation in other
loci used to characterize the phylogeographic histories of these Arctic-alpine
species.
PMID- 24348899
TI - Using a search engine-based mutually reinforcing approach to assess the semantic
relatedness of biomedical terms.
AB - BACKGROUND: Determining the semantic relatedness of two biomedical terms is an
important task for many text-mining applications in the biomedical field.
Previous studies, such as those using ontology-based and corpus-based approaches,
measured semantic relatedness by using information from the structure of
biomedical literature, but these methods are limited by the small size of
training resources. To increase the size of training datasets, the outputs of
search engines have been used extensively to analyze the lexical patterns of
biomedical terms. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we propose the
Mutually Reinforcing Lexical Pattern Ranking (ReLPR) algorithm for learning and
exploring the lexical patterns of synonym pairs in biomedical text. ReLPR employs
lexical patterns and their pattern containers to assess the semantic relatedness
of biomedical terms. By combining sentence structures and the linking activities
between containers and lexical patterns, our algorithm can explore the
correlation between two biomedical terms. CONCLUSIONS/SIGNIFICANCE: The average
correlation coefficient of the ReLPR algorithm was 0.82 for various datasets. The
results of the ReLPR algorithm were significantly superior to those of previous
methods.
PMID- 24348898
TI - Identification of unstable network modules reveals disease modules associated
with the progression of Alzheimer's disease.
AB - Alzheimer's disease (AD), the most common cause of dementia, is associated with
aging, and it leads to neuron death. Deposits of amyloid beta and aberrantly
phosphorylated tau protein are known as pathological hallmarks of AD, but the
underlying mechanisms have not yet been revealed. A high-throughput gene
expression analysis previously showed that differentially expressed genes
accompanying the progression of AD were more down-regulated than up-regulated in
the later stages of AD. This suggested that the molecular networks and their
constituent modules collapsed along with AD progression. In this study, by using
gene expression profiles and protein interaction networks (PINs), we identified
the PINs expressed in three brain regions: the entorhinal cortex (EC),
hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs
into modules, we examined the stability of the modules with AD progression and
with normal aging. We found that in the AD modules, the constituent proteins,
interactions and cellular functions were not maintained between consecutive
stages through all brain regions. Interestingly, the modules were collapsed with
AD progression, specifically in the EC region. By identifying the modules that
were affected by AD pathology, we found the transcriptional regulation-associated
modules that interact with the proteasome-associated module via UCHL5 hub
protein, which is a deubiquitinating enzyme. Considering PINs as a system made of
network modules, we found that the modules relevant to the transcriptional
regulation are disrupted in the EC region, which affects the ubiquitin-proteasome
system.
PMID- 24348900
TI - Transcriptional activation of the cholecystokinin gene by DJ-1 through
interaction of DJ-1 with RREB1 and the effect of DJ-1 on the cholecystokinin
level in mice.
AB - DJ-1 is an oncogene and also causative gene for familial Parkinson's disease. DJ
1 has multiple functions, including transcriptional regulation. DJ-1 acts as a
coactivator that binds to various transcription factors, resulting in stimulation
or repression of the expression of their target genes. In this study, we found
that the cholecystokinin (CCK) gene is a transcriptional target gene for DJ-1.
CCK is a peptide hormone and plays roles in contraction of the gallbladder and in
promotion of secretion of pancreatic fluid. CCK is co-localized with dopamine in
the substantia nigra to regulate release of dopamine. Reduced expression of CCK
mRNA was observed in DJ-1-knockdown cells. The Ras-responsive element (RRE) and
Sp1 site were essential for promoter activity, and DJ-1 stimulated promoter
activity by binding to RRE-binding protein 1 (RREBP1). The complex of DJ-1 with
RREB1 but not with Sp1 bound to the RRE. Furthermore, the reduced CCK level in
the serum from DJ-1-knockout mice compared to that from wild-type mice was
observed. This is the first report showing that DJ-1 participates in peptide
hormone synthesis.
PMID- 24348901
TI - Identification of three antiviral inhibitors against Japanese encephalitis virus
from library of pharmacologically active compounds 1280.
AB - Japanese encephalitis virus (JEV) can cause severe central nervous disease with a
high mortality rate. There is no antiviral drug available for JEV-specific
treatment. In this study, a cytopathic-effect-based, high-throughput screening
assay was developed and applied to screen JEV inhibitors from Library of
Pharmacologically Active Compounds 1280. The antiviral effects of three hit
compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in
cells by western blotting, indirect immunofluorescence assay, and plaque
reduction assay. A time-of-addition assay proved that all three compounds
inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine,
and niclosamide were 3.21, 6.52, and 5.80 uM, respectively, while the selectivity
indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high
efficiency and selectivity against JEV. This study provided two JEV antiviral
inhibitors as candidates for treatment of JEV infection.
PMID- 24348902
TI - Measuring the reliability of picture story exercises like the TAT.
AB - As frequently reported, psychometric assessments on Picture Story Exercises,
especially variations of the Thematic Apperception Test, mostly reveal inadequate
scores for internal consistency. We demonstrate that the reason for this apparent
shortcoming is not caused by the coding system itself but from the incorrect use
of internal consistency coefficients, especially Cronbach's alpha. This problem
could be eliminated by using the category-scores as items instead of the picture
scores. In addition to a theoretical explanation we prove mathematically why the
use of category-scores produces an adequate internal consistency estimation and
examine our idea empirically with the origin data set of the Thematic
Apperception Test by Heckhausen and two additional data sets. We found generally
higher values when using the category-scores as items instead of picture-scores.
From an empirical and theoretical point of view, the estimated reliability is
also superior to each category within a picture as item measuring. When comparing
our suggestion with a multifaceted Rasch-model we provide evidence that our
procedure better fits the underlying principles of PSE.
PMID- 24348904
TI - Early re-do surgery for glioblastoma is a feasible and safe strategy to achieve
complete resection of enhancing tumor.
AB - BACKGROUND: Complete resection of enhancing tumor as assessed by early (<72
hours) postoperative MRI is regarded as the optimal result in glioblastoma
surgery. As yet, there is no consensus on standard procedure if post-operative
imaging reveals unintended tumor remnants. OBJECTIVE: The current study evaluated
the feasibility and safety of an early re-do surgery aimed at completing
resections with the aid of 5-ALA fluorescence and neuronavigation after detection
of enhancing tumor remnants on post-operative MRI. METHODS: From October 2008 to
October 2012 a single center institutional protocol offered a second surgery
within one week to patients with unintentional incomplete glioblastoma resection.
We report on the feasibility of the use 5-ALA fluorescence guidance, the extent
of resection (EOR) rates and complications of early re-do surgery. RESULTS: Nine
of 151 patients (6%) with glioblastoma resections had an unintentional tumor
remnant with a volume >0.175 cm(3). 5-ALA guided re-do surgery completed the
resection (CRET) in all patients without causing neurological deficits,
infections or other complications. Patients who underwent a re-do surgery
remained hospitalized between surgeries, resulting in a mean length of hospital
stay of 11 days (range 7-15), compared to 9 days for single surgery (range 3-23;
p=0.147). CONCLUSION: Our early re-do protocol led to complete resection of all
enhancing tumor in all cases without any new neurological deficits and thus
provides a similar oncological result as intraoperative MRI (iMRI). The repeated
use of 5-ALA induced fluorescence, used for identification of small remnants,
remains highly sensitive and specific in the setting of re-do surgery. Early re
do surgery is a feasible and safe strategy to complete unintended subtotal
resections.
PMID- 24348903
TI - A p53 drug response signature identifies prognostic genes in high-risk
neuroblastoma.
AB - Chemotherapy induces apoptosis and tumor regression primarily through activation
of p53-mediated transcription. Neuroblastoma is a p53 wild type malignancy at
diagnosis and repression of p53 signaling plays an important role in its
pathogenesis. Recently developed small molecule inhibitors of the MDM2-p53
interaction are able to overcome this repression and potently activate p53
dependent apoptosis in malignancies with intact p53 downstream signaling. We used
the small molecule MDM2 inhibitor, Nutlin-3a, to determine the p53 drug response
signature in neuroblastoma cells. In addition to p53 mediated apoptotic
signatures, GSEA and pathway analysis identified a set of p53-repressed genes
that were reciprocally over-expressed in neuroblastoma patients with the worst
overall outcome in multiple clinical cohorts. Multifactorial regression analysis
identified a subset of four genes (CHAF1A, RRM2, MCM3, and MCM6) whose expression
together strongly predicted overall and event-free survival (p<0.0001). The
expression of these four genes was then validated by quantitative PCR in a large
independent clinical cohort. Our findings further support the concept that
oncogene-driven transcriptional networks opposing p53 activation are essential
for the aggressive behavior and poor response to therapy of high-risk
neuroblastoma.
PMID- 24348905
TI - Food availability and maternal immunization affect transfer and persistence of
maternal antibodies in nestling pigeons.
AB - The ability of mothers to transfer antibodies (Abs) to their young and the
temporal persistence of maternal Abs in offspring constitute important life
history traits that can impact the evolution of host-parasite interactions. Here,
we examined the effects of food availability and parental immunization on the
transfer and persistence of maternal antibodies in nestling pigeons (Columba
livia). This species can transmit maternal Abs to offspring before hatching
through the egg yolk and potentially after hatching through crop milk. However,
the role of this postnatal substance in immunity remains elusive. We used a full
cross-fostering design to disentangle the effects of food limitation and parental
immunization both before and after hatching on the levels and persistence of
maternal Abs in chicks. Parents were immunized via injection with keyhole limpet
hemocyanin antigens. Using an immunoassay that specifically detected the IgY
antibodies that are known to be transmitted via the yolk, we found that the
levels of anti-KLH Abs in newly hatched chicks were positively correlated with
the levels of anti-KLH Abs in the blood of their biological mothers. However,
this correlation was not present between chicks and their foster parents,
suggesting limited IgY transfer via crop milk to the chick's bloodstream.
Interestingly, biological mothers subjected to food limitation during egg laying
transferred significantly fewer specific maternal Abs, which suggests that the
transfer of antibodies might be costly for them. In addition, the persistence of
maternal Abs in a chick's bloodstream was not affected by food limitation or the
foster parents' anti-KLH Ab levels; it was only affected by the initial level of
maternal anti-KLH Abs that were present in newly hatched chicks. These results
suggest that the maternal transfer of Abs could be costly but that their
persistence in an offspring's bloodstream may not necessarily be affected by
environmental conditions.
PMID- 24348906
TI - Negative node count improvement prognostic prediction of the seventh edition of
the TNM classification for gastric cancer.
AB - OBJECTIVE: To demonstrate that the seventh edition of the tumor-node-metastasis
(TNM) classification for gastric cancer (GC) should be updated with the number of
negative lymph nodes for the improvement of its prognostic prediction accuracy.
METHODS: Clinicopathological data of 769 GC patients who underwent curative
gastrectomy with lymphadenectomy between 1997 and 2006 were retrospectively
analyzed to demonstrate the superiority of prognostic efficiency of the seventh
edition of the TNM classification, which can be improved by combining the number
of negative lymph nodes. RESULTS: With the Cox regression multivariate analysis,
the seventh edition of the TNM classification, the number of negative nodes, the
type of gastrectomy, and the depth of tumor invasion (T stage) were identified as
independent factors for predicting the overall survival of GC patients.
Furthermore, we confirmed that the T stage-N stage-number of negative lymph nodes
metastasis (TNnM) classification is the most appropriate prognostic predictor of
GC patients by using case-control matched fashion and multinominal logistic
regression. Finally, we were able to clarify that TNnM classification may provide
more precise survival differences among the different TNM sub-stages of GC by
using the measure of agreement (Kappa coefficient), the McNemar value, the Akaike
information criterion, and the Bayesian Information Criterion compared with the
seventh edition of the TNM classification. CONCLUSION: The number of negative
nodes, as an important prognostic predictor of GC, can improve the prognostic
prediction efficiency of the seventh edition of the TNM classification for GC,
which should be recommended for conventional clinical applications.
PMID- 24348907
TI - iTRAQ-based proteomic analysis of polyploid giant cancer cells and budding
progeny cells reveals several distinct pathways for ovarian cancer development.
AB - Polyploid giant cancer cells (PGCCs) are a morphologically distinct subgroup of
human tumor cells with increased nuclear size or multiple nuclei, but they are
generally considered unimportant because they are presumed to be nondividing and
thus nonviable. We have recently shown that these large cancer cells are not only
viable but also can divide asymmetrically and yield progeny cancer cells with
cancer stem-like properties via budding division. To further understand the
molecular events involved in the regulation of PGCCs and the generation of their
progeny cancer cells, we comparatively analyzed the proteomic profiles of PGCCs,
PGCCs with budding daughter cells, and regular control cancer cells from the HEY
and SKOv3 human ovarian cancer cell lines with and without CoCl2. We used a high
throughput iTRAQ-based proteomic methodology coupled with liquid chromatography
electrospray ionization tandem mass spectroscopy to determine the differentiated
regulated proteins. We performed Western blotting and immunohistochemical
analyses to validate the differences in the expression patterns of a variety of
proteins between PGCCs or budding PGCCs and regular cancer cells identified by
iTRAQ approach and also a selected group of proteins from the literature. The
differentially regulated proteins included proteins involved in response to
hypoxia, stem cell generation, chromatin remodeling, cell-cycle regulation, and
invasion and metastasis. In particular, we found that HIF-1alpha and its known
target STC1 are upregulated in PGCCs. In addition, we found that a panel of stem
cell-regulating factors and epithelial-to-mesenchymal transition regulatory
transcription factors were upregulated in budding PGCCs, whereas expression of
the histone 1 family of nucleosomal linker proteins was consistently lower in
PGCCs than in control cells. Thus, proteomic expression patterns provide valuable
insight into the underlying mechanisms of PGCC formation and the relationship
between PGCCs and cancer stem cells in patients with ovarian cancers.
PMID- 24348908
TI - Distinct optical chemistry of dissolved organic matter in urban pond ecosystems.
AB - Urbanization has the potential to dramatically alter the biogeochemistry of
receiving freshwater ecosystems. We examined the optical chemistry of dissolved
organic matter (DOM) in forty-five urban ponds across southern Ontario, Canada to
examine whether optical characteristics in these relatively new ecosystems are
distinct from other freshwater systems. Dissolved organic carbon (DOC)
concentrations ranged from 2 to 16 mg C L(-1) across the ponds with an average
value of 5.3 mg C L(-1). Excitation-emission matrix (EEM) spectroscopy and
parallel factor analysis (PARAFAC) modelling showed urban pond DOM to be
characterized by microbial-like and, less importantly, by terrestrial derived
humic-like components. The relatively transparent, non-humic DOM in urban ponds
was more similar to that found in open water, lake ecosystems than to rivers or
wetlands. After irradiation equivalent to 1.7 days of natural solar radiation,
DOC concentrations, on average, decreased by 38% and UV absorbance decreased by
25%. Irradiation decreased the relative abundances of terrestrial humic-like
components and increased protein-like aspects of the DOM pool. These findings
suggest that high internal production and/or prolonged exposure to sunlight
exerts a distinct and significant influence on the chemistry of urban pond DOM,
which likely reduces its chemical similarity with upstream sources. These
properties of urban pond DOM may alter its biogeochemical role in these
relatively novel aquatic ecosystems.
PMID- 24348909
TI - Trying to move your unseen static arm modulates visually-evoked kinesthetic
illusion.
AB - Although kinesthesia is known to largely depend on afferent inflow, recent data
suggest that central signals originating from volitional control (efferent
outflow) could also be involved and interact with the former to build up a
coherent percept. Evidence derives from both clinical and experimental
observations where vision, which is of primary importance in kinesthesia, was
systematically precluded. The purpose of the present experiment was to assess the
role of volitional effort in kinesthesia when visual information is available.
Participants (n=20) produced isometric contraction (10-20% of maximal voluntary
force) of their right arm while their left arm, which image was reflected in a
mirror, either was passively moved into flexion/extension by a motorized
manipulandum, or remained static. The contraction of the right arm was either
congruent with or opposite to the passive displacements of the left arm. Results
revealed that in most trials, kinesthetic illusions were visually driven, and
their occurrence and intensity were modulated by whether volitional effort was
congruent or not with visual signals. These results confirm the impact of
volitional effort in kinesthesia and demonstrate for the first time that these
signals interact with visual afferents to offer a coherent and unified percept.
PMID- 24348910
TI - Transcriptional regulation of two conceptus interferon tau genes expressed in
Japanese black cattle during peri-implantation period.
AB - Interferon tau (IFNT), produced by the mononuclear trophectoderm, signals the
process of maternal recognition of pregnancy in ruminants. However, its
expression in vivo and its transcriptional regulation are not yet well
characterized. Objectives of this study were to determine conceptus IFNT gene
isoforms expressed in the bovine uterus and to identify differences in promoter
sequences of IFNT genes that differ in their expression. RNA-seq data analysis of
bovine conceptuses on days 17, 20, and 22 (day 0 = day of estrus) detected the
expression of two IFNT transcripts, IFNT1 and IFNTc1, which were indeed
classified into the IFNT gene clade. RNA-seq and quantitative RT-PCR analyses
also revealed that the expression levels of both IFNT mRNAs were highest on day
17, and then decreased on days 20 and 22. Bovine ear-derived fibroblast (EF)
cells, a model system commonly used for bovine IFNT gene transcription study in
this laboratory, were cotransfected with luciferase reporter constructs carrying
upstream (positions -637 to +51) regions of IFNT1 or IFNTc1 gene and various
transcription factor expression plasmids including CDX2, AP-1 (Jun) and ETS2.
CDX2, either alone or with the other transcription factors, markedly increased
luciferase activity. The upstream regions of IFNT1 and IFNTc1 loci were then
serially deleted or point-mutated at potential CDX-, AP-1-, and ETS-binding
sites. Compared to the wild-type constructs, deletion or mutation at CDX2 or ETS2
binding sites similarly reduced the luciferase activities of IFNT1- or IFNTc1
promoter constructs. However, with the AP-1 site mutated construct, IFNT1- and
IFNTc1-reporters behaved differently. These results suggest that two forms of
bovine conceptus IFNT genes are expressed in utero and their transcriptional
regulations differ.
PMID- 24348911
TI - Associations between lifetime traumatic events and subsequent chronic physical
conditions: a cross-national, cross-sectional study.
AB - BACKGROUND: Associations between lifetime traumatic event (LTE) exposures and
subsequent physical ill-health are well established but it has remained unclear
whether these are explained by PTSD or other mental disorders. This study
examined this question and investigated whether associations varied by type and
number of LTEs, across physical condition outcomes, or across countries. METHODS:
Cross-sectional, face-to-face household surveys of adults (18+) were conducted in
14 countries (n = 38, 051). The Composite International Diagnostic Interview
assessed lifetime LTEs and DSM-IV mental disorders. Chronic physical conditions
were ascertained by self-report of physician's diagnosis and year of diagnosis or
onset. Survival analyses estimated associations between the number and type of
LTEs with the subsequent onset of 11 physical conditions, with and without
adjustment for mental disorders. FINDINGS: A dose-response association was found
between increasing number of LTEs and odds of any physical condition onset (OR
1.5 [95% CI: 1.4-1.5] for 1 LTE; 2.1 [2.0-2.3] for 5+ LTEs), independent of all
mental disorders. Associations did not vary greatly by type of LTE (except for
combat and other war experience), nor across countries. A history of 1 LTE was
associated with 7/11 of the physical conditions (ORs 1.3 [1.2-1.5] to 1.7 [1.4
2.0]) and a history of 5+ LTEs was associated with 9/11 physical conditions (ORs
1.8 [1.3-2.4] to 3.6 [2.0-6.5]), the exceptions being cancer and stroke.
CONCLUSIONS: Traumatic events are associated with adverse downstream effects on
physical health, independent of PTSD and other mental disorders. Although the
associations are modest they have public health implications due to the high
prevalence of traumatic events and the range of common physical conditions
affected. The effects of traumatic stress are a concern for all medical
professionals and researchers, not just mental health specialists.
PMID- 24348912
TI - Modulation of intracellular calcium waves and triggered activities by
mitochondrial ca flux in mouse cardiomyocytes.
AB - Recent studies have suggested that mitochondria may play important roles in the
Ca(2+) homeostasis of cardiac myocytes. However, it is still unclear if
mitochondrial Ca(2+) flux can regulate the generation of Ca(2+) waves (CaWs) and
triggered activities in cardiac myocytes. In the present study,
intracellular/cytosolic Ca(2+) (Cai (2+)) was imaged in Fluo-4-AM loaded mouse
ventricular myocytes. Spontaneous sarcoplasmic reticulum (SR) Ca(2+) release and
CaWs were induced in the presence of high (4 mM) external Ca(2+) (Cao (2+)). The
protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP)
reversibly raised basal Cai (2+) levels even after depletion of SR Ca(2+) in the
absence of Cao (2+) , suggesting Ca(2+) release from mitochondria. FCCP at 0.01 -
0.1 uM partially depolarized the mitochondrial membrane potential (Deltapsi m )
and increased the frequency and amplitude of CaWs in a dose-dependent manner.
Simultaneous recording of cell membrane potentials showed the augmentation of
delayed afterdepolarization amplitudes and frequencies, and induction of
triggered action potentials. The effect of FCCP on CaWs was mimicked by antimycin
A (an electron transport chain inhibitor disrupting Deltapsi m ) or Ru360 (a
mitochondrial Ca(2+) uniporter inhibitor), but not by oligomycin (an ATP synthase
inhibitor) or iodoacetic acid (a glycolytic inhibitor), excluding the
contribution of intracellular ATP levels. The effects of FCCP on CaWs were
counteracted by the mitochondrial permeability transition pore blocker
cyclosporine A, or the mitochondrial Ca(2+) uniporter activator kaempferol. Our
results suggest that mitochondrial Ca(2+) release and uptake exquisitely control
the local Ca(2+) level in the micro-domain near SR ryanodine receptors and play
an important role in regulation of intracellular CaWs and arrhythmogenesis.
PMID- 24348913
TI - Deterministic diffusion fiber tracking improved by quantitative anisotropy.
AB - Diffusion MRI tractography has emerged as a useful and popular tool for mapping
connections between brain regions. In this study, we examined the performance of
quantitative anisotropy (QA) in facilitating deterministic fiber tracking. Two
phantom studies were conducted. The first phantom study examined the
susceptibility of fractional anisotropy (FA), generalized factional anisotropy
(GFA), and QA to various partial volume effects. The second phantom study
examined the spatial resolution of the FA-aided, GFA-aided, and QA-aided
tractographies. An in vivo study was conducted to track the arcuate fasciculus,
and two neurosurgeons blind to the acquisition and analysis settings were invited
to identify false tracks. The performance of QA in assisting fiber tracking was
compared with FA, GFA, and anatomical information from T1-weighted images. Our
first phantom study showed that QA is less sensitive to the partial volume
effects of crossing fibers and free water, suggesting that it is a robust index.
The second phantom study showed that the QA-aided tractography has better
resolution than the FA-aided and GFA-aided tractography. Our in vivo study
further showed that the QA-aided tractography outperforms the FA-aided, GFA
aided, and anatomy-aided tractographies. In the shell scheme (HARDI), the FA
aided, GFA-aided, and anatomy-aided tractographies have 30.7%, 32.6%, and 24.45%
of the false tracks, respectively, while the QA-aided tractography has 16.2%. In
the grid scheme (DSI), the FA-aided, GFA-aided, and anatomy-aided tractographies
have 12.3%, 9.0%, and 10.93% of the false tracks, respectively, while the QA
aided tractography has 4.43%. The QA-aided deterministic fiber tracking may
assist fiber tracking studies and facilitate the advancement of human
connectomics.
PMID- 24348914
TI - The transcriptomics of glucocorticoid receptor signaling in developing zebrafish.
AB - Cortisol is the primary corticosteroid in teleosts that is released in response
to stressor activation of the hypothalamus-pituitary-interrenal axis. The target
tissue action of this hormone is primarily mediated by the intracellular
glucocorticoid receptor (GR), a ligand-bound transcription factor. In developing
zebrafish (Danio rerio) embryos, GR transcripts and cortisol are maternally
deposited into the oocyte prior to fertilization and influence early
embryogenesis. To better understand of the molecular mechanisms involved, we
investigated changes in the developmental transcriptome prior to hatch, in
response to morpholino oligonucleotide knockdown of GR using the Agilent
zebrafish microarray platform. A total of 1313 and 836 mRNA transcripts were
significantly changed at 24 and 36 hours post fertilization (hpf), respectively.
Functional analysis revealed numerous developmental processes under GR
regulation, including neurogenesis, eye development, skeletal and cardiac muscle
formation. Together, this study underscores a critical role for glucocorticoid
signaling in programming molecular events essential for zebrafish development.
PMID- 24348915
TI - Effect of artificial selection on runs of homozygosity in u.s. Holstein cattle.
AB - The intensive selection programs for milk made possible by mass artificial
insemination increased the similarity among the genomes of North American (NA)
Holsteins tremendously since the 1960s. This migration of elite alleles has
caused certain regions of the genome to have runs of homozygosity (ROH)
occasionally spanning millions of continuous base pairs at a specific locus. In
this study, genome signatures of artificial selection in NA Holsteins born
between 1953 and 2008 were identified by comparing changes in ROH between three
distinct groups under different selective pressure for milk production. The ROH
regions were also used to estimate the inbreeding coefficients. The comparisons
of genomic autozygosity between groups selected or unselected since 1964 for milk
production revealed significant differences with respect to overall ROH frequency
and distribution. These results indicate selection has increased overall
autozygosity across the genome, whereas the autozygosity in an unselected line
has not changed significantly across most of the chromosomes. In addition, ROH
distribution was more variable across the genomes of selected animals in
comparison to a more even ROH distribution for unselected animals. Further
analysis of genome-wide autozygosity changes and the association between traits
and haplotypes identified more than 40 genomic regions under selection on several
chromosomes (Chr) including Chr 2, 7, 16 and 20. Many of these selection
signatures corresponded to quantitative trait loci for milk, fat, and protein
yield previously found in contemporary Holsteins.
PMID- 24348916
TI - Antigenic and genetic diversity of human enterovirus 71 from 2009 to 2012,
Taiwan.
AB - Different subgenogroups of enterovirus 71 (EV-71) have caused numerous outbreaks
of hand, foot, and mouth disease worldwide, especially in the Asia-Pacific
region. During the development of a vaccine against EV-71, the genetic and
antigenic diversities of EV-71 isolates from Taiwan were analyzed by phylogenetic
analyses and neutralization tests. The results showed that the dominant
genogroups had changed twice, from B to C and from C to B, between 2009 and 2012.
The subgenogroup B5 (B5b cluster) was dominant in 2008-2009 but was replaced by
subgenogroup C4 in 2010-2011. From the end of 2011 to 2012, the re-emerging
subgenogroup B5 (B5c cluster) was identified as the dominant subgenogroup of EV
71 outbreaks, and subgenogroups C2 and C4 were detected in sporadic cases.
Interestingly, the amino acid substitution at position 145 in the VP1 gene was
observed in some strains isolated from patients with acute flaccid paralysis.
Furthermore, thirty-five strains and their corresponding serum samples were used
to analyze the cross-protections and antigenic diversities among different
subgenogroups (C4a, C5, B4, B5b, B5c, and C2-like) of EV-71. Evident antigenic
diversity existed only for the C2-like subgenogroup, which was not effectively
neutralized by other serum samples. In contrast, the anti-C2-like serum sample
showed broad cross-reactivity against all other subgenogroups. Therefore, these
results may provide valuable information for the selection of EV-71 vaccine
candidates and the evolution of EV-71 subgenogroups in Taiwan from 2009 to 2012.
PMID- 24348918
TI - New paleocene sepiid coleoids (cephalopoda) from Egypt: evolutionary significance
and origin of the sepiid 'rostrum'.
AB - New coleoid cephalopods, assignable to the order Sepiida, are recorded from the
Selandian/Thanetian boundary interval (Middle to Upper Paleocene transition, c.
59.2 Ma) along the southeastern margin (Toshka Lakes) of the Western Desert in
Egypt. The two genera recognised, Aegyptosaepia n. gen. and ?Anomalosaepia Weaver
and Ciampaglio, are placed in the families Belosaepiidae and ?Anomalosaepiidae,
respectively. They constitute the oldest record to date of sepiids with a
'rostrum-like' prong. In addition, a third, generically and specifically
indeterminate coleoid is represented by a single rostrum-like find. The taxonomic
assignment of the material is based on apical parts (as preserved), i.e., guard,
apical prong (or 'rostrum-like' structure), phragmocone and (remains of)
protoconch, plus shell mineralogy. We here confirm the shell of early sepiids to
have been bimineralic, i.e., composed of both calcite and aragonite.
Aegyptosaepia lugeri n. gen., n. sp. reveals some similarities to later species
of Belosaepia, in particular the possession of a distinct prong. General features
of the phragmocone and protoconch of the new form are similar to both Belocurta
(Middle Danian [Lower Paleocene]) and Belosaepia (Eocene). However, breviconic
coiling and the presence of a longer ventral conotheca indicate closer ties with
late Maastrichtian-Middle Danian Ceratisepia. In this respect, Aegyptosaepia n.
gen. constitutes a link between Ceratisepia and the Eocene Belosaepia. The
occurrence of the new genus near the Selandian/Thanetian boundary suggests an
earlier origin of belosaepiids, during the early to Middle Paleocene. These
earliest known belosaepiids may have originated in the Tethyan Realm. From
northeast Africa, they subsequently spread to western India, the Arabian Plate
and, probably via the Mediterranean region, to Europe and North America.
PMID- 24348919
TI - Light suppresses sporulation and epidemics of Peronospora belbahrii.
AB - Peronospora belbahrii is a biotrophic oomycete attacking sweet basil. It
propagates asexually by producing spores on dichotomously branched sporophores
emerging from leaf stomata. Sporulation occurs when infected plants are incubated
for at least 7.5h in the dark in moisture-saturated atmosphere at 10-27 degrees
C. Exposure to light suppresses spore formation but allows sporophores to emerge
from stomata. Incandescent or CW fluorescent light of 3.5 or 6 umoles.m(2).s(-1)
respectively, caused 100% inhibition of spore formation on lower leaf surface
even when only the upper leaf surface was exposed to light. The inhibitory effect
of light failed to translocate from an illuminated part of a leaf to a shaded
part of the same leaf. Inhibition of sporulation by light was temperature
dependent. Light was fully inhibitory at 15-27 degrees C but not at 10 degrees C,
suggesting that enzyme(s) activity and/or photoreceptor protein re-arrangement
induced by light occur at >=15 degrees C. DCMU or paraquat could not abolish
light inhibition, indicating that photosystem I and photosystem II are not
involved. Narrow band led illumination showed that red light (lambdamax 625 nm)
was most inhibitory and blue light (lambdamax 440 nm) was least inhibitory,
suggesting that inhibition in P. belbahrii, unlike other oomycetes, operates via
a red light photoreceptor. Nocturnal illumination of basil in the field (4-10
umoles.m(2).s(-1) from 7pm to 7am) suppressed sporulation of P. belbahrii and
reduced epidemics of downy mildew, thus reducing the need for fungicide
applications. This is the first report on red light inhibition of sporulation in
oomycetes and on the practical application of light for disease control in the
field.
PMID- 24348917
TI - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic
challenges.
AB - The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found
widely in nature and it is exploited in industrial processes for the
manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its
varied natural habitats and in industrial settings, B. licheniformis cells will
be exposed to increases in the external osmolarity, conditions that trigger water
efflux, impair turgor, cause the cessation of growth, and negatively affect the
productivity of cell factories in biotechnological processes. We have taken here
both systems-wide and targeted physiological approaches to unravel the core of
the osmostress responses of B. licheniformis. Cells were suddenly subjected to an
osmotic upshift of considerable magnitude (with 1 M NaCl), and their
transcriptional profile was then recorded in a time-resolved fashion on a genome
wide scale. A bioinformatics cluster analysis was used to group the osmotically
up-regulated genes into categories that are functionally associated with the
synthesis and import of osmostress-relieving compounds (compatible solutes), the
SigB-controlled general stress response, and genes whose functional annotation
suggests that salt stress triggers secondary oxidative stress responses in B.
licheniformis. The data set focusing on the transcriptional profile of B.
licheniformis was enriched by proteomics aimed at identifying those proteins that
were accumulated by the cells through increased biosynthesis in response to
osmotic stress. Furthermore, these global approaches were augmented by a set of
experiments that addressed the synthesis of the compatible solutes proline and
glycine betaine and assessed the growth-enhancing effects of various
osmoprotectants. Combined, our data provide a blueprint of the cellular
adjustment processes of B. licheniformis to both sudden and sustained osmotic
stress.
PMID- 24348920
TI - Attenuation of eph receptor kinase activation in cancer cells by coexpressed
ephrin ligands.
AB - The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting "in
trans" with ligands anchored to the surface of neighboring cells via a GPI-anchor
(ephrin-As) or a transmembrane segment (ephrin-Bs), which leads to receptor
clustering and increased kinase activity. Additionally, soluble forms of the
ephrin-A ligands released from the cell surface by matrix metalloproteases can
also activate EphA receptor signaling. Besides these trans interactions, recent
studies have revealed that Eph receptors and ephrins coexpressed in neurons can
also engage in lateral "cis" associations that attenuate receptor activation by
ephrins in trans with critical functional consequences. Despite the importance of
the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have
not been previously investigated in cancer cells. Here we show that in cancer
cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind
ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4
but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some
cases ephrins that cannot activate a particular Eph receptor in trans can
nevertheless inhibit its signaling ability through cis association. We also found
that an EphA3 mutation identified in lung cancer enhances cis interaction with
ephrin-A3. These results suggest a novel mechanism that may contribute to cancer
pathogenesis by attenuating the tumor suppressing effects of Eph receptor
signaling pathways activated by ephrins in trans.
PMID- 24348921
TI - The Panhandle formed by influenza A and C virus NS non-coding regions determines
NS segment expression.
AB - Exchange of the extremities of the NS segment of type A and C influenza viruses
in reverse genetics systems was used to assess their putative role in type
specificity. Restoration of each specific proximal panhandle was mandatory to
allow the rescue of viruses with heterotypic extremities. Moreover, the
transcription level of the modified segment seemed to be directly affected by the
distal panhandle strength.
PMID- 24348922
TI - Systems approaches to animal disease surveillance and resource allocation:
methodological frameworks for behavioral analysis.
AB - While demands for animal disease surveillance systems are growing, there has been
little applied research that has examined the interactions between resource
allocation, cost-effectiveness, and behavioral considerations of actors
throughout the livestock supply chain in a surveillance system context. These
interactions are important as feedbacks between surveillance decisions and
disease evolution may be modulated by their contextual drivers, influencing the
cost-effectiveness of a given surveillance system. This paper identifies a number
of key behavioral aspects involved in animal health surveillance systems and
reviews some novel methodologies for their analysis. A generic framework for
analysis is discussed, with exemplar results provided to demonstrate the utility
of such an approach in guiding better disease control and surveillance decisions.
PMID- 24348983
TI - Absence of suction feeding ichthyosaurs and its implications for triassic
mesopelagic paleoecology.
AB - Mesozoic marine reptiles and modern marine mammals are often considered
ecological analogs, but the extent of their similarity is largely unknown.
Particularly important is the presence/absence of deep-diving suction feeders
among Mesozoic marine reptiles because this would indicate the establishment of
mesopelagic cephalopod and fish communities in the Mesozoic. A recent study
suggested that diverse suction feeders, resembling the extant beaked whales,
evolved among ichthyosaurs in the Triassic. However, this hypothesis has not been
tested quantitatively. We examined four osteological features of jawed
vertebrates that are closely linked to the mechanism of suction feeding, namely
hyoid corpus ossification/calcification, hyobranchial apparatus robustness,
mandibular bluntness, and mandibular pressure concentration index. Measurements
were taken from 18 species of Triassic and Early Jurassic ichthyosaurs, including
the presumed suction feeders. Statistical comparisons with extant sharks and
marine mammals of known diets suggest that ichthyosaurian hyobranchial bones are
significantly more slender than in suction-feeding sharks or cetaceans but
similar to those of ram-feeding sharks. Most importantly, an ossified hyoid
corpus to which hyoid retractor muscles attach is unknown in all but one
ichthyosaur, whereas a strong integration of the ossified corpus and cornua of
the hyobranchial apparatus has been identified in the literature as an important
feature of suction feeders. Also, ichthyosaurian mandibles do not narrow rapidly
to allow high suction pressure concentration within the oral cavity, unlike in
beaked whales or sperm whales. In conclusion, it is most likely that Triassic and
Early Jurassic ichthyosaurs were 'ram-feeders', without any beaked-whale-like
suction feeder among them. When combined with the inferred inability for dim
light vision in relevant Triassic ichthyosaurs, the fossil record of ichthyosaurs
does not suggest the establishment of modern-style mesopelagic animal communities
in the Triassic. This new interpretation matches the fossil record of coleoids,
which indicates the absence of soft-bodied deepwater species in the Triassic.
PMID- 24348984
TI - ReacKnock: identifying reaction deletion strategies for microbial strain
optimization based on genome-scale metabolic network.
AB - Gene knockout has been used as a common strategy to improve microbial strains for
producing chemicals. Several algorithms are available to predict the target
reactions to be deleted. Most of them apply mixed integer bi-level linear
programming (MIBLP) based on metabolic networks, and use duality theory to
transform bi-level optimization problem of large-scale MIBLP to single-level
programming. However, the validity of the transformation was not proved. Solution
of MIBLP depends on the structure of inner problem. If the inner problem is
continuous, Karush-Kuhn-Tucker (KKT) method can be used to reformulate the MIBLP
to a single-level one. We adopt KKT technique in our algorithm ReacKnock to
attack the intractable problem of the solution of MIBLP, demonstrated with the
genome-scale metabolic network model of E. coli for producing various chemicals
such as succinate, ethanol, threonine and etc. Compared to the previous methods,
our algorithm is fast, stable and reliable to find the optimal solutions for all
the chemical products tested, and able to provide all the alternative deletion
strategies which lead to the same industrial objective.
PMID- 24348986
TI - Multiple Sclerosis in the Mount Etna region: possible role of volcanogenic trace
elements.
AB - BACKGROUND: Trace elements have been hypothesised to be involved in the
pathogenesis of Multiple Sclerosis and volcanic degassing is the major natural
sources of trace elements. Both incidence of Multiple Sclerosis in Catania and
volcanic activity of Mount Etna have been significantly increased during the last
30 years. Due to prevailing trade winds direction, volcanic gases from Etna
summit craters are mostly blown towards the eastern and southern sectors of the
volcano. OBJECTIVE: To evaluate the possible association between Multiple
Sclerosis and exposure to volcanogenic trace elements. METHODS: We evaluated
prevalence and incidence of Multiple Sclerosis in four communities (47,234
inhabitants) located in the eastern flank and in two communities (52,210
inhabitants) located in the western flank of Mount Etna, respectively the most
and least exposed area to crater gas emissions. RESULTS: A higher prevalence was
found in the population of the eastern flank compared to the population of the
western one (137.6/100,000 versus 94.3/100,000; p-value 0.04). We found a
borderline significantly higher incidence risk during the incidence study period
(1980-2009) in the population of the eastern flank 4.6/100,000 (95% CI 3.1-5.9),
compared with the western population 3.2/100,000 (95% CI 2.4-4.2) with a RR of
1.41 (95% CI 0.97-2.05; p-value 0.06). Incidence risks have increased over the
time in both populations reaching a peak of 6.4/100,000 in the eastern flank and
of 4.4/100.000 in the western flank during 2000-2009. CONCLUSION: We found a
higher prevalence and incidence of Multiple Sclerosis among populations living in
the eastern flank of Mount Etna. According to our data a possible role of TE
cannot be ruled out as possible co-factor in the MS pathogenesis. However larger
epidemiological study are needed to confirm this hypothesis.
PMID- 24348985
TI - Risk of severe upper gastrointestinal complications among oral bisphosphonate
users.
AB - BACKGROUND: Oral bisphosphonates (BPs) are the primary agents for the treatment
of osteoporosis. Although BPs are generally well tolerated, serious
gastrointestinal adverse events have been observed. AIM: To assess the risk of
severe upper gastrointestinal complications (UGIC) among BP users by means of a
large study based on a network of Italian healthcare utilization databases.
METHODS: A nested case-control study was carried out by including 110,220
patients aged 45 years or older who, from 2003 until 2005, were treated with oral
BPs. Cases were the 862 patients who experienced the outcome (hospitalization for
UGIC) until 2007. Up to 20 controls were randomly selected for each case.
Conditional logistic regression model was used to estimate odds ratio (OR)
associated with current use of BPs after adjusting for several covariates. A set
of sensitivity analyses was performed in order to account for sources of
systematic uncertainty. RESULTS: The adjusted OR for current use of BPs with
respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that
this risk changed either with BP type and regimen, or concurrent use of other
drugs or previous hospitalizations. CONCLUSIONS: No evidence was found that
current use of BPs increases the risk of severe upper gastrointestinal
complications compared to past use.
PMID- 24348988
TI - Association between gestational weight gain and postpartum diabetes: evidence
from a community based large cohort study.
AB - We have investigated the prospective association between excess gestational
weight gain (GWG) and development of diabetes by 21 years post-partum using a
community-based large prospective cohort study in Brisbane, Australia. There were
3386 mothers for whom complete data were available on GWG, pre-pregnancy BMI and
self-reported diabetes 21 years post-partum. We used The Institute of Medicine
(IOM) definition to categorize GWG as inadequate, adequate and excessive. We
found 839 (25.78%) mothers gained inadequate weight, 1,353 (39.96%) had adequate
weight gain and 1,194 (35.26%) had gained excessive weight during pregnancy. At
21 years post-partum, 8.40% of mothers self-reported a diagnosis of diabetes made
by their doctor. In the age adjusted model, we found mothers who gained excess
weight during pregnancy were 1.47 (1.11,1.94) times more likely to experience
diabetes at 21 years post-partum compared to the mothers who gained adequate
weight. This association was not explained by the potential confounders including
maternal age, parity, education, race, smoking, TV watching and exercise.
However, this association was mediated by the current BMI. There was no
association for the women who had normal BMI before pregnancy and gained excess
weight during pregnancy. The findings of this study suggest that women who gain
excess weight during pregnancy are at greater risk of being diagnosed with
diabetes in later life. This relationship is likely mediated through the pathway
of post-partum weight-retention and obesity. This study adds evidence to the
argument that excessive GWG during pregnancy for overweight mothers has long term
maternal health implications.
PMID- 24348987
TI - Site-specific keloid fibroblasts alter the behaviour of normal skin and normal
scar fibroblasts through paracrine signalling.
AB - Keloid disease (KD) is an abnormal cutaneous fibroproliferative disorder of
unknown aetiopathogenesis. Keloid fibroblasts (KF) are implicated as mediators of
elevated extracellular matrix deposition. Aberrant secretory behaviour by KF
relative to normal skin fibroblasts (NF) may influence the disease state. To
date, no previous reports exist on the ability of site-specific KF to induce
fibrotic-like phenotypic changes in NF or normal scar fibroblasts (NS) by
paracrine mechanisms. Therefore, the aim of this study was to investigate the
influence of conditioned media from site-specific KF on the cellular and
molecular behaviour of both NF and NS enabled by paracrine mechanisms.
Conditioned media was collected from cultured primary fibroblasts during a
proliferative log phase of growth including: NF, NS, peri-lesional keloid
fibroblasts (PKF) and intra-lesional keloid fibroblasts (IKF). Conditioned media
was used to grow NF, NS, PKF and IKF cells over 240 hrs. Cellular behavior was
monitored through real time cell analysis (RTCA), proliferation rates and
migration in a scratch wound assay. Fibrosis-associated marker expression was
determined at both protein and gene level. PKF conditioned media treatment of
both NF and NS elicited enhanced cell proliferation, spreading and viability as
measured in real time over 240 hrs versus control conditioned media. Following
PKF and IKF media treatments up to 240 hrs, both NF and NS showed significantly
elevated proliferation rates (p<0.03) and migration in a scratch wound assay
(p<0.04). Concomitant up-regulation of collagen I, fibronectin, alpha-SMA, PAI-1,
TGF-beta and CTGF (p<0.03) protein expression were also observed. Corresponding
qRT-PCR analysis supported these findings (P<0.03). In all cases, conditioned
media from growing marginal PKF elicited the strongest effects. In conclusion,
primary NF and NS cells treated with PKF or IKF conditioned media exhibit
enhanced expression of fibrosis-associated molecular markers and increased
cellular activity as a result of keloid fibroblast-derived paracrine factors.
PMID- 24348989
TI - Baseline levels and temporal stability of 27 multiplexed serum cytokine
concentrations in healthy subjects.
AB - BACKGROUND: Cytokines are humoral molecules that elicit regulatory function in
immunologic pathways. The level and type of cytokine production has become
critical in distinguishing physiologic from pathologic immune conditions.
Cytokine profiling has become an important biomarker discovery tool in monitoring
of the immune system. However, the variations in cytokine levels in individual
subjects over time in healthy individuals have not been extensively studied. In
this study, we use multiplex bead arrays to evaluate 27 analytes in paired serum
samples taken seven days apart from 144 healthy individuals in order to assess
variations over a short time period. METHODS: Fluorescent bead-based immunoassay
(Luminex) was used to measure 27 analytes in serum samples. Measurements were
performed on matched samples from 144 healthy donors. To assess inter-plate
variability, one arbitrarily selected serum sample was analyzed on each of the
first ten plates as bridge sample. RESULTS: Using the bridge sample, we showed
minimal inter-plate variations in the measurement of most analytes. In
measurement of cytokines from the 144 patients at two time points, we found that
three cytokines (IL-2, IL-15 and GM-CSF) were undetectable and five analytes
(RANTES, MCP-1, VEGF, MIP-1beta and PDGF-BB) showed significant difference in
concentrations at Day 0 compared to Day 7. CONCLUSIONS: The current study
demonstrated higher variations in cytokine levels among individuals than were
observed for samples obtained one week apart from identical donors. These data
suggest that a serum sample from each subject for use as a baseline measurement
is a better control for clinical trials rather than sera from a paired cohort.
PMID- 24348992
TI - Human-assisted spread of a maladaptive behavior in a critically endangered bird.
AB - Conservation management often focuses on counteracting the adverse effects of
human activities on threatened populations. However, conservation measures may
unintentionally relax selection by allowing the 'survival of the not-so-fit',
increasing the risk of fixation of maladaptive traits. Here, we report such a
case in the critically-endangered Chatham Island black robin (Petroica traversi)
which, in 1980, was reduced to a single breeding pair. Following this bottleneck,
some females were observed to lay eggs on the rims of their nests. Rim eggs left
in place always failed to hatch. To expedite population recovery, rim eggs were
repositioned inside nests, yielding viable hatchlings. Repositioning resulted in
rapid growth of the black robin population, but by 1989 over 50% of all females
were laying rim eggs. We used an exceptional, species-wide pedigree to consider
both recessive and dominant models of inheritance over all plausible founder
genotype combinations at a biallelic and possibly sex-linked locus. The pattern
of rim laying is best fitted as an autosomal dominant Mendelian trait. Using a
phenotype permutation test we could also reject the null hypothesis of non
heritability for this trait in favour of our best-fitting model of heritability.
Data collected after intervention ceased shows that the frequency of rim laying
has strongly declined, and that this trait is maladaptive. This episode yields an
important lesson for conservation biology: fixation of maladaptive traits could
render small threatened populations completely dependent on humans for
reproduction, irreversibly compromising the long term viability of populations
humanity seeks to conserve.
PMID- 24348990
TI - Essential function of dynamin in the invasive properties and actin architecture
of v-Src induced podosomes/invadosomes.
AB - The large GTPase dynamin plays a key role in endocytosis but is also localized at
numerous actin rich sites. We investigated dynamin functions at
podosomes/invadosomes, actin-based cellular adhesion structures implicated in
tissue invasion. Podosomes/invadosomes are constituted of long F-actin bundles
perpendicular to the substratum (actin cores), connected to randomly arranged F
actin fibers parallel to the substratum (actin cloud). We show here that dynamin
depletion in v-Src-transformed fibroblasts triggers a massive disorganization of
podosomes/invadosomes (isolated or in rosettes), with a corresponding inhibition
of their invasive properties. The action of dynamin at podosomes/invadosomes
requires a functional full-length protein, suggesting that the effects of dynamin
at these sites and in membrane remodelling during endocytosis are mediated by
similar mechanisms. In order to determine direct effect of dynamin depletion on
invadosome, an optogenetic approach based on the photosensitizer KillerRed was
developed. Acute dynamin photo-inactivation leads to a very rapid disorganization
of invadosome without affecting focal adhesions. Dynamin therefore is a key
regulator of the architecture of actin in podosomes/invadosomes.
PMID- 24348991
TI - Individual differences in brain structure and resting brain function underlie
cognitive styles: evidence from the Embedded Figures Test.
AB - Cognitive styles can be characterized as individual differences in the way people
perceive, think, solve problems, learn, and relate to others. Field
dependence/independence (FDI) is an important and widely studied dimension of
cognitive styles. Although functional imaging studies have investigated the brain
activation of FDI cognitive styles, the combined structural and functional
correlates with individual differences in a large sample have never been
investigated. In the present study, we investigated the neural correlates of
individual differences in FDI cognitive styles by analyzing the correlations
between Embedded Figures Test (EFT) score and structural neuroimaging data
[regional gray matter volume (rGMV) was assessed using voxel-based morphometry
(VBM)]/functional neuroimaging data [resting-brain functions were measured by
amplitude of low-frequency fluctuation (ALFF)] throughout the whole brain.
Results showed that the increased rGMV in the left inferior parietal lobule (IPL)
was associated with the EFT score, which might be the structural basis of
effective local processing. Additionally, a significant positive correlation
between ALFF and EFT score was found in the fronto-parietal network, including
the left inferior parietal lobule (IPL) and the medial prefrontal cortex (mPFC).
We speculated that the left IPL might be associated with superior feature
identification, and mPFC might be related to cognitive inhibition of global
processing bias. These results suggested that the underlying neuroanatomical and
functional bases were linked to the individual differences in FDI cognitive
styles and emphasized the important contribution of superior local processing
ability and cognitive inhibition to field-independent style.
PMID- 24348993
TI - Mortality attributable to influenza in England and Wales prior to, during and
after the 2009 pandemic.
AB - Very different influenza seasons have been observed from 2008/09-2011/12 in
England and Wales, with the reported burden varying overall and by age group. The
objective of this study was to estimate the impact of influenza on all-cause and
cause-specific mortality during this period. Age-specific generalised linear
regression models fitted with an identity link were developed, modelling weekly
influenza activity through multiplying clinical influenza-like illness
consultation rates with proportion of samples positive for influenza A or B. To
adjust for confounding factors, a similar activity indicator was calculated for
Respiratory Syncytial Virus. Extreme temperature and seasonal trend were
controlled for. Following a severe influenza season in 2008/09 in 65+yr olds
(estimated excess of 13,058 influenza A all-cause deaths), attributed all-cause
mortality was not significant during the 2009 pandemic in this age group and
comparatively low levels of influenza A mortality were seen in post-pandemic
seasons. The age shift of the burden of seasonal influenza from the elderly to
young adults during the pandemic continued into 2010/11; a comparatively larger
impact was seen with the same circulating A(H1N1)pdm09 strain, with the burden of
influenza A all-cause excess mortality in 15-64 yr olds the largest reported
during 2008/09-2011/12 (436 deaths in 15-44 yr olds and 1,274 in 45-64 yr olds).
On average, 76% of seasonal influenza A all-age attributable deaths had a
cardiovascular or respiratory cause recorded (average of 5,849 influenza A deaths
per season), with nearly a quarter reported for other causes (average of 1,770
influenza A deaths per season), highlighting the importance of all-cause as well
as cause-specific estimates. No significant influenza B attributable mortality
was detected by season, cause or age group. This analysis forms part of the
preparatory work to establish a routine mortality monitoring system ahead of
introduction of the UK universal childhood seasonal influenza vaccination
programme in 2013/14.
PMID- 24348994
TI - Topic structure affects semantic integration: evidence from event-related
potentials.
AB - This study investigated whether semantic integration in discourse context could
be influenced by topic structure using event-related brain potentials.
Participants read discourses in which the last sentence contained a critical word
that was either congruent or incongruent with the topic established in the first
sentence. The intervening sentences between the first and the last sentence of
the discourse either maintained or shifted the original topic. Results showed
that incongruent words in topic-maintained discourses elicited an N400 effect
that was broadly distributed over the scalp while those in topic-shifted
discourses elicited an N400 effect that was lateralized to the right hemisphere
and localized over central and posterior areas. Moreover, a late positivity
effect was only elicited by incongruent words in topic-shifted discourses, but
not in topic-maintained discourses. This suggests an important role for discourse
structure in semantic integration, such that compared with topic-maintained
discourses, the complexity of discourse structure in topic-shifted condition
reduces the initial stage of semantic integration and enhances the later stage in
which a mental representation is updated.
PMID- 24348995
TI - Antibiotic stewardship ward rounds and a dedicated prescription chart reduce
antibiotic consumption and pharmacy costs without affecting inpatient mortality
or re-admission rates.
AB - BACKGROUND: Antibiotic consumption is a major driver of bacterial resistance. To
address the increasing burden of multi-drug resistant bacterial infections,
antibiotic stewardship programmes are promoted worldwide to rationalize
antibiotic prescribing and conserve remaining antibiotics. Few studies have been
reported from developing countries and none from Africa that report on an
intervention based approach with outcomes that include morbidity and mortality.
METHODS: An antibiotic prescription chart and weekly antibiotic stewardship ward
round was introduced into two medical wards of an academic teaching hospital in
South Africa between January-December 2012. Electronic pharmacy records were used
to collect the volume and cost of antibiotics used, the patient database was
analysed to determine inpatient mortality and 30-day re-admission rates, and
laboratory records to determine use of infection-related tests. Outcomes were
compared to a control period, January-December 2011. RESULTS: During the
intervention period, 475.8 defined daily doses were prescribed per 1000 inpatient
days compared to 592.0 defined daily doses/1000 inpatient days during the control
period. This represents a 19.6% decrease in volume with a cost reduction of 35%
of the pharmacy's antibiotic budget. There was a concomitant increase in
laboratory tests driven by requests for procalcitonin. There was no difference in
inpatient mortality or 30-day readmission rate during the control and
intervention periods. CONCLUSIONS: Introduction of antibiotic stewardship ward
rounds and a dedicated prescription chart in a developing country setting can
achieve reduction in antibiotic consumption without harm to patients. Increased
laboratory costs should be anticipated when introducing an antibiotic stewardship
program.
PMID- 24348996
TI - Mechanisms of hemagglutinin targeted influenza virus neutralization.
AB - Human monoclonal antibodies have been identified which neutralize broad spectra
of influenza A or B viruses. Here, we dissect the mechanisms by which such
antibodies interfere with infectivity. We distinguish four mechanisms that link
the conserved hemagglutinin (HA) epitopes of broadly neutralizing antibodies to
critical processes in the viral life cycle. HA-stem binding antibodies can act
intracellularly by blocking fusion between the viral and endosomal membranes and
extracellularly by preventing the proteolytic activation of HA. HA-head binding
antibodies prevent viral attachment and release. These insights into newly
identified ways by which the human immune system can interfere with influenza
virus infection may aid the development of novel universal vaccines and
antivirals.
PMID- 24348997
TI - A small RNA encoded in the Rv2660c locus of Mycobacterium tuberculosis is induced
during starvation and infection.
AB - Enhanced transcription of the Rv2660c locus in response to starvation of
Mycobacterium tuberculosis H37Rv encouraged addition of the predicted Rv2660c
protein to an improved vaccine formulation. Using strand-specific RNA sequencing,
we show that the up-regulated transcript is in fact a small RNA encoded on the
opposite strand to the annotated Rv2660c. The transcript originates within a
prophage and is expressed only in strains that carry PhiRv2. The small RNA
contains both host and phage sequences and provides a useful biomarker to monitor
bacterial starvation during infection and/or non-replicating persistence. Using
different approaches we do not find any evidence of Rv2660c at the level of mRNA
or protein. Further efforts to understand the mechanism by which Rv2660c improves
efficacy of the H56 vaccine are likely to provide insights into the pathology and
immunology of tuberculosis.
PMID- 24348998
TI - Genetic analysis of low BMI phenotype in the Utah Population Database.
AB - The low body mass index (BMI) phenotype of less than 18.5 has been linked to
medical and psychological morbidity as well as increased mortality risk. Although
genetic factors have been shown to influence BMI across the entire BMI, the
contribution of genetic factors to the low BMI phenotype is unclear. We
hypothesized genetic factors would contribute to risk of a low BMI phenotype. To
test this hypothesis, we conducted a genealogy data analysis using height and
weight measurements from driver's license data from the Utah Population Data
Base. The Genealogical Index of Familiality (GIF) test and relative risk in
relatives were used to examine evidence for excess relatedness among individuals
with the low BMI phenotype. The overall GIF test for excess relatedness in the
low BMI phenotype showed a significant excess over expected (GIF 4.47 for all
cases versus 4.10 for controls, overall empirical p-value<0.001). The significant
excess relatedness was still observed when close relationships were ignored,
supporting a specific genetic contribution rather than only a family
environmental effect. This study supports a specific genetic contribution in the
risk for the low BMI phenotype. Better understanding of the genetic contribution
to low BMI holds promise for weight regulation and potentially for novel
strategies in the treatment of leanness and obesity.
PMID- 24348999
TI - Zoos through the lens of the IUCN Red List: a global metapopulation approach to
support conservation breeding programs.
AB - Given current extinction trends, the number of species requiring conservation
breeding programs (CBPs) is likely to increase dramatically. To inform CBP
policies for threatened terrestrial vertebrates, we evaluated the number and
representation of threatened vertebrate species on the IUCN Red List held in the
ISIS zoo network and estimated the complexity of their management as
metapopulations. Our results show that 695 of the 3,955 (23%) terrestrial
vertebrate species in ISIS zoos are threatened. Only two of the 59 taxonomic
orders show a higher proportion of threatened species in ISIS zoos than would be
expected if species were selected at random. In addition, for most taxa, the
management of a zoo metapopulation of more than 250 individuals will require the
coordination of a cluster of 11 to 24 ISIS zoos within a radius of 2,000 km.
Thus, in the zoo network, the representation of species that may require CBPs is
currently low and the spatial distribution of these zoo populations makes
management difficult. Although the zoo community may have the will and the
logistical potential to contribute to conservation actions, including CBPs, to do
so will require greater collaboration between zoos and other institutions,
alongside the development of international agreements that facilitate cross
border movement of zoo animals. To maximize the effectiveness of integrated
conservation actions that include CBPs, it is fundamental that the non-zoo
conservation community acknowledges and integrates the expertise and facilities
of zoos where it can be helpful.
PMID- 24349000
TI - Strong genetic influence on a UK nationwide test of educational achievement at
the end of compulsory education at age 16.
AB - We have previously shown that individual differences in educational achievement
are highly heritable in the early and middle school years in the UK. The
objective of the present study was to investigate whether similarly high
heritability is found at the end of compulsory education (age 16) for the UK-wide
examination, called the General Certificate of Secondary Education (GCSE). In a
national twin sample of 11,117 16-year-olds, heritability was substantial for
overall GCSE performance for compulsory core subjects (58%) as well as for each
of them individually: English (52%), mathematics (55%) and science (58%). In
contrast, the overall effects of shared environment, which includes all family
and school influences shared by members of twin pairs growing up in the same
family and attending the same school, accounts for about 36% of the variance of
mean GCSE scores. The significance of these findings is that individual
differences in educational achievement at the end of compulsory education are not
primarily an index of the quality of teachers or schools: much more of the
variance of GCSE scores can be attributed to genetics than to school or family
environment. We suggest a model of education that recognizes the important role
of genetics. Rather than a passive model of schooling as instruction (instruere,
'to build in'), we propose an active model of education (educare, 'to bring out')
in which children create their own educational experiences in part on the basis
of their genetic propensities, which supports the trend towards personalized
learning.
PMID- 24349001
TI - Dissociated neurons and glial cells derived from rat inferior colliculi after
digestion with papain.
AB - The formation of gliosis around implant electrodes for deep brain stimulation
impairs electrode-tissue interaction. Unspecific growth of glial tissue around
the electrodes can be hindered by altering physicochemical material properties.
However, in vitro screening of neural tissue-material interaction requires an
adequate cell culture system. No adequate model for cells dissociated from the
inferior colliculus (IC) has been described and was thus the aim of this study.
Therefore, IC were isolated from neonatal rats (P3_5) and a dissociated cell
culture was established. In screening experiments using four dissociation methods
(Neural Tissue Dissociation Kit [NTDK] T, NTDK P; NTDK PN, and a validated
protocol for the dissociation of spiral ganglion neurons [SGN]), the optimal
media, and seeding densities were identified. Thereafter, a dissociation protocol
containing only the proteolytic enzymes of interest (trypsin or papain) was
tested. For analysis, cells were fixed and immunolabeled using glial- and neuron
specific antibodies. Adhesion and survival of dissociated neurons and glial cells
isolated from the IC were demonstrated in all experimental settings. Hence,
preservation of type-specific cytoarchitecture with sufficient neuronal networks
only occurred in cultures dissociated with NTDK P, NTDK PN, and fresh prepared
papain solution. However, cultures obtained after dissociation with papain,
seeded at a density of 2*10(4) cells/well and cultivated with Neuro Medium for 6
days reliably revealed the highest neuronal yield with excellent cytoarchitecture
of neurons and glial cells. The herein described dissociated culture can be
utilized as in vitro model to screen interactions between cells of the IC and
surface modifications of the electrode.
PMID- 24349002
TI - Sialylation and muscle performance: sialic acid is a marker of muscle ageing.
AB - Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic
glycoconjugates. They are involved in many cellular functions, such as cell-cell
interaction and signal recognition. The key enzyme of sialic acid biosynthesis is
the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase
(GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol. In
this study we analysed sialylation of muscles in wild type (C57Bl/6 GNE (+/+))
and heterozygous GNE-deficient (C57Bl/6 GNE (+/-)) mice. We measured a
significantly lower performance in the initial weeks of a treadmill exercise in
C57Bl/6 GNE (+/-) mice compared to wild type C57Bl/6 GNE (+/+) animals. Membrane
bound Sia of C57Bl/6 GNE (+/-) mice were reduced by 33-53% at week 24 and by 12
15% at week 80 in comparison to C57Bl/6 GNE (+/+) mice. Interestingly, membrane
bound Sia concentration increased with age of the mice by 16-46% in C57Bl/6 GNE
(+/+), but by 87-207% in C57Bl/6 GNE (+/-). Furthermore we could identify
specific morphological changes in aged muscles. Here we propose that increased
Sia concentrations in muscles are a characteristic feature of ageing and could be
used as a marker for age-related changes in muscle.
PMID- 24349003
TI - Vaginal immunization to elicit primary T-cell activation and dissemination.
AB - Primary T-cell activation at mucosal sites is of utmost importance for the
development of vaccination strategies. T-cell priming after vaginal immunization,
with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine
formulation, was studied in vivo in hormone-synchronized mice and compared to the
one induced by the nasal route. Twenty-four hours after both vaginal or nasal
immunization, antigen-loaded dendritic cells were detected within the respective
draining lymph nodes. Vaginal immunization elicited a strong recruitment of
antigen-specific CD4(+) T cells into draining lymph nodes that was more rapid
than the one observed following nasal immunization. T-cell clonal expansion was
first detected in iliac lymph nodes, draining the genital tract, and proliferated
T cells disseminated towards distal lymph nodes and spleen similarly to what
observed following nasal immunization. T cells were indeed activated by the
antigen encounter and acquired homing molecules essential to disseminate towards
distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and
CD62L marker expression. A multi-type Galton Watson branching process, previously
used for in vitro analysis of T-cell proliferation, was applied to model in vivo
CFSE proliferation data in draining lymph nodes 57 hours following immunization,
in order to calculate the probabilistic decision of a cell to enter in division,
rest in quiescence or migrate/die. The modelling analysis indicated that the
probability of a cell to proliferate was higher following vaginal than nasal
immunization. All together these data show that vaginal immunization, despite the
absence of an organized mucosal associated inductive site in the genital tract,
is very efficient in priming antigen-specific CD4(+) T cells and inducing their
dissemination from draining lymph nodes towards distal lymphoid organs.
PMID- 24349004
TI - ESAT-6 (EsxA) and TB10.4 (EsxH) based vaccines for pre- and post-exposure
tuberculosis vaccination.
AB - The ESX systems from Mycobacterium tuberculosis are responsible for the secretion
of highly immunogenic proteins of key importance for bacterial survival and
growth. The two prototypic proteins, ESAT-6 (EsxA from ESX-1) and TB10.4 (EsxH
from ESX-3) share a lot of characteristics regarding genome organization, size,
antigenic properties, and vaccine potential but the two molecules clearly have
very different roles in bacterial physiology. To further investigate the role of
ESAT-6 and TB10.4 as preventive and post-exposure tuberculosis vaccines, we
evaluated four different fusion-protein vaccines; H1, H4, H56 and H28, that
differ only in these two components. We found that all of these vaccines give
rise to protection in a conventional prophylactic vaccination model. In contrast,
only the ESAT-6-containing vaccines resulted in significant protection against
reactivation, when administered post-exposure. This difference in post-exposure
activity did not correlate with a difference in gene expression during infection
or a differential magnitude or quality of the vaccine-specific CD4 T cells
induced by ESAT-6 versus TB10.4-containing vaccines. The post-exposure effect of
the ESAT-6 based vaccines was found to be influenced by the infectious load at
the time-point of vaccination and was abolished in chronically infected animals
with high bacterial loads at the onset of vaccination. Our data demonstrate that
there are specific requirements for the immune system to target an already
established tuberculosis infection and that ESAT-6 has a unique potential in post
exposure vaccination strategies.
PMID- 24349005
TI - Phylogenetic relatedness of circulating HIV-1C variants in Mochudi, Botswana.
AB - BACKGROUND: Determining patterns of HIV transmission is increasingly important
for the most efficient use of modern prevention interventions. HIV phylogeny can
provide a better understanding of the mechanisms underlying HIV transmission
networks in communities. METHODS: To reconstruct the structure and dynamics of a
local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env
sequences obtained from 785 HIV-infected community residents in the northeastern
sector of Mochudi, Botswana, during 2010-2013 was estimated. The genotyping
coverage was estimated at 44%. Clusters were defined based on relatedness of HIV
1C env sequences and bootstrap support of splits. RESULTS: The overall proportion
of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The
proportion of clustered sequences from Mochudi was significantly higher than the
proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12;
Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI
85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences
from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At
least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were
enumerated, and their sequence signatures were reconstructed. Seven of 20
genotyped seroconverters were found in 7 distinct clusters. CONCLUSIONS: The
study provides essential characteristics of the HIV transmission network in a
community in Botswana, suggests the importance of high sampling coverage, and
highlights the need for broad HIV genotyping to determine the spread of community
unique and community-mixed viral variants circulating in local epidemics. The
proposed methodology of cluster analysis enumerates circulating HIV variants and
can work well for surveillance of HIV transmission networks. HIV genotyping at
the community level can help to optimize and balance HIV prevention strategies in
trials and combined intervention packages.
PMID- 24349006
TI - Breast cancer mortality vs. exercise and breast size in runners and walkers.
AB - PURPOSE: Identify predictors of breast cancer mortality in women who exercised
below (<7.5 metabolic equivalent hours/week, MET-hours/wk), at (7.5 to 12.5 MET
hours/wk), or above (>=12.5 MET-hours/wk) recommended levels. METHODS: Cox
proportional hazard analyses of baseline pre-diagnosis MET-hours/wk vs. breast
cancer mortality adjusted for follow-up age, race, baseline menopause, and
estrogen and oral contraceptive use in 79,124 women (32,872 walkers, 46,252
runners) from the National Walkers' and Runners' Health Studies. RESULTS: One
hundred eleven women (57 walkers, 54 runners) died from breast cancer during the
11-year follow-up. The decline in mortality in women who exercised >=7.5 MET
hours/wk was not different for walking and running (P = 0.34), so running and
walking energy expenditures were combined. The risk for breast cancer mortality
was 41.5% lower for >=7.5 vs. <7.5 MET-hours/wk (HR: 0.585, 95%CI: 0.382 to
0.924, P = 0.02), which persisted when adjusted for BMI (HR: 0.584, 95%CI: 0.368
to 0.956, P = 0.03). Other than age and menopause, baseline bra cup size was the
strongest predictor of breast cancer mortality, i.e., 57.9% risk increase per cup
size when adjusted for MET-hours/wk and the other covariates (HR: 1.579, 95%CI:
1.268 to 1.966, P<0.0001), and 70.4% greater when further adjusted for BMI (HR:
1.704, 95%CI: 1.344 to 2.156, P = 10(-5)). Breast cancer mortality was 4.0-fold
greater (HR: 3.980, 95%CI: 1.894 to 9.412, P = 0.0001) for C-cup, and 4.7-fold
greater (HR: 4.668, 95%CI: 1.963 to 11.980, P = 0.0004) for >=D-cup vs. A-cup
when adjusted for BMI and other covariates. Adjustment for cup size and BMI did
not eliminate the association between breast cancer mortality and >=7.5 MET
hour/wk walked or run (HR: 0.615, 95%CI: 0.389 to 1.004, P = 0.05). CONCLUSION:
Breast cancer mortality decreased in association with both meeting the exercise
recommendations and smaller breast volume.
PMID- 24349007
TI - Performance of rapid point-of-care and laboratory tests for acute and established
HIV infection in San Francisco.
AB - BACKGROUND: Current laboratory and point-of-care tests for HIV detect different
analytes and use different sample types. Some have fast turnaround times (<1
hour). We investigated how HIV test choice could impact case finding by testing
programs. METHODS: We analyzed 21,234 consecutive HIV tests with venous blood
obtained by San Francisco HIV testing programs from 2003 to 2008. For a subset,
oral fluid (n = 6446) or fingerstick blood (n = 8127) samples were also obtained
for rapid testing. In all cases, HIV status was determined using an HIV antibody
plus-RNA test algorithm. We assessed how the screening antibody tests performed
individually versus the gold standard of the full algorithm. We then evaluated
the potential ability of other tests (including new tests) to detect more cases,
by re-testing all specimens that had negative/discrepant antibody results on
initial screening. FINDINGS: The antibody-RNA algorithm identified 58 acute and
703 established HIV infection cases. 1(st)-generation (Vironostika) and 3(rd)
generation (Genetic Systems) immunoassays had 92 and 96 percent sensitivity,
respectively. The Oraquick rapid test had clinical sensitivity of only 86 percent
on oral fluid samples, but 92 percent on finger-stick blood. Newer 4(th)
generation, antigen-antibody combo rapid immunoassay (ARCHITECT) detected HIV in
87 percent of all the acute cases that had been missed by one of the previous
screening assays. A point-of-care 4(th) generation antigen-antibody combo rapid
test (Determine) detected about 54 percent of such acute cases. CONCLUSIONS: Our
study suggests that some rapid antibody blood tests will give similar case
detection to laboratory antibody tests, but that oral fluid testing greatly
reduces ability to detect HIV. New 4(th)-generation combo tests can detect the
majority of acute infections detectable by HIV RNA but with rapid results. Using
these tests as a primary screening assay in high-risk HIV testing programs could
reduce or eliminate the need for HIV RNA testing.
PMID- 24349008
TI - The alpha and Delta isoforms of CREB1 are required to maintain normal pulmonary
vascular resistance.
AB - Chronic hypoxia causes pulmonary hypertension associated with structural
alterations in pulmonary vessels and sustained vasoconstriction. The
transcriptional mechanisms responsible for these distinctive changes are unclear.
We have previously reported that CREB1 is activated in the lung in response to
alveolar hypoxia but not in other organs. To directly investigate the role of
alpha and Delta isoforms of CREB1 in the regulation of pulmonary vascular
resistance we examined the responses of mice in which these isoforms of CREB1 had
been inactivated by gene mutation, leaving only the beta isoform intact
(CREB(alphaDelta) mice). Here we report that expression of CREB regulated genes
was altered in the lungs of CREB(alphaDelta) mice. CREB(alphaDelta) mice had
greater pulmonary vascular resistance than wild types, both basally in normoxia
and following exposure to hypoxic conditions for three weeks. There was no
difference in rho kinase mediated vasoconstriction between CREB(alphaDelta) and
wild type mice. Stereological analysis of pulmonary vascular structure showed
characteristic wall thickening and lumen reduction in hypoxic wild-type mice,
with similar changes observed in CREB(alphaDelta). CREB(alphaDelta) mice had
larger lungs with reduced epithelial surface density suggesting increased
pulmonary compliance. These findings show that alpha and Delta isoforms of CREB1
regulate homeostatic gene expression in the lung and that normal activity of
these isoforms is essential to maintain low pulmonary vascular resistance in both
normoxic and hypoxic conditions and to maintain the normal alveolar structure.
Interventions that enhance the actions of alpha and Delta isoforms of CREB1
warrant further investigation in hypoxic lung diseases.
PMID- 24349009
TI - Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury
through the sphingosine kinase/sphingosine 1-phosphate axis.
AB - OBJECTIVE: Experimental and clinical studies have shown that administration of
insulin during reperfusion is cardioprotective, but the mechanisms underlying
this effect are still unknown. In this study, the ability of insulin to protect
apoptotic cardiomyocytes from hypoxia/reoxygenation injury using the sphingosine
kinase/sphingosine 1-phosphate axis was investigated. METHODS AND RESULTS: Rat
cardiomyocytes were isolated and subjected to hypoxia and reoxygenation. [gamma
32P] ATP was used to assess sphingosine kinase activity. Insulin was found to
increase sphingosine kinase activity. Immunocytochemistry and Western blot
analysis showed changes in the subcellular location of sphingosine kinase 1 from
cytosol to the membrane in cardiomyocytes. Insulin caused cardiomyocytes to
accumulate of S1P in a dose-dependent manner. FRET efficiency showed that insulin
also transactivates the S1P1 receptor. TUNEL staining showed that administration
of insulin during reoxygenation could to reduce the rate of reoxygenation-induced
apoptosis, which is a requirement for SphK 1 activity. It also reduced the rate
of activation of the S1P receptor and inhibited hypoxia/reoxygenation-induced
cell death in cardiomyocytes. CONCLUSION: The sphingosine kinase 1/sphingosine 1
phosphate/S1P receptor axis is one pathway through which insulin protects rat
cardiomyocytes from apoptosis induced by hypoxia/reoxygenation injury.
PMID- 24349010
TI - Predicting survival after liver transplantation based on pre-transplant MELD
score: a systematic review of the literature.
AB - The model for end-stage liver disease (MELD) score is used to stratify candidates
for liver transplantation based on objective measures of disease severity. MELD
has been validated as a predictor of wait-list mortality in transplantation
candidates and has been postulated as a predictor of post-transplant survival.
The purpose of this study was to examine the predictive value of the pre
transplantation MELD score on post-transplant survival from relevant existing
studies. A systematic review and critical appraisal was performed using Cochrane
guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were
searched for articles published in the English language since 2005 using a
structured search strategy. There were 3058 discrete citations identified and
screened for possible inclusion. Any study examining the relationship between pre
transplant MELD and post-transplant survival in the general transplant population
was included. Thirty-seven studies met these criteria and were included in the
review. Studies were all case series that typically involved stratified analyses
of survival by MELD. They represented 15 countries and a total of 53,691
patients. There was significant clinical heterogeneity in patient populations
across studies, which precluded performance of a meta-analysis. In 15 studies, no
statistically significant association between MELD and post-transplant survival
was found. In the remaining 22, some association was found. Eleven studies also
measured predictive ability with c-statistics. Values were below 0.7 in all but
two studies, suggesting poor predictive value. In summary, while the majority of
studies reported an association between pre-transplantation MELD score and post
transplant survival, they represented a low level of evidence. Therefore, their
findings should be interpreted conservatively.
PMID- 24349011
TI - Capsular types of Klebsiella pneumoniae revisited by wzc sequencing.
AB - Capsule is an important virulence factor in bacteria. A total of 78 capsular
types have been identified in Klebsiella pneumoniae. However, there are
limitations in current typing methods. We report here the development of a new
genotyping method based on amplification of the variable regions of the wzc gene.
Fragments corresponding to the variable region of wzc were amplified and
sequenced from 76 documented capsular types of reference or clinical strains. The
remaining two capsular types (reference strains K15 and K50) lacked amplifiable
wzc genes and were proven to be acapsular. Strains with the same capsular type
exhibited ?94% DNA sequence identity across the variable region (CD1-VR2-CD2) of
wzc. Strains with distinct K types exhibited <80% DNA sequence identity across
this region, with the exception of three pairs of strains: K22/K37, K9/K45, and
K52/K79. Strains K22 and K37 shared identical capsular polysaccharide synthesis
(cps) genes except for one gene with a difference at a single base which resulted
in frameshift mutation. The wzc sequences of K9 and K45 exhibited high DNA
sequence similarity but possessed different genes in their cps clusters. K52 and
K79 exhibited 89% wzc DNA sequence identity but were readily distinguished from
each other at the DNA level; in contrast, strains with the same capsular type as
K52 exhibited 100% wzc sequence identity. A total of 29 strains from patients
with bacteremia were typed by the wzc system. wzc DNA sequences confirmed the
documented capsular type for twenty-eight of these clinical isolates; the
remaining strain likely represents a new capsular type. Thus, the wzc genotyping
system is a simple and useful method for capsular typing of K. pneumoniae.
PMID- 24349012
TI - TLR2 ligands induce NF-kappaB activation from endosomal compartments of human
monocytes.
AB - Localization of Toll-like receptors (TLR) in subcellular organelles is a major
strategy to regulate innate immune responses. While TLR4, a cell-surface
receptor, signals from both the plasma membrane and endosomal compartments, less
is known about the functional role of endosomal trafficking upon TLR2 signaling.
Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-kappaB
dependent signaling from endosomal compartments in human monocytes and in a NF
kappaB sensitive reporter cell line, despite the expression of TLR2 at the cell
surface. Further analyses indicate that TLR2-induced NF-kappaB activation is
controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14
serves as an important upstream regulator. These findings establish that
internalization of cell-surface TLR2 into endosomal compartments is required for
NF-kappaB activation. These observations further demonstrate the need of
endocytosis in the activation and regulation of TLR2-dependent signaling
pathways.
PMID- 24349013
TI - Long range linkage disequilibrium across the human genome.
AB - Long-range linkage disequilibria (LRLD) between sites that are widely separated
on chromosomes may suggest that population admixture, epistatic selection, or
other evolutionary forces are at work. We quantified patterns of LRLD on a
chromosome-wide level in the YRI population of the HapMap dataset of single
nucleotide polymorphisms (SNPs). We calculated the disequilibrium between all
pairs of SNPs on each chromosome (a total of >2*10(11) values) and evaluated
significance of overall disequilibrium using randomization. The results show an
excess of associations between pairs of distant sites (separated by >0.25 cM) on
all of the 22 autosomes. We discuss possible explanations for this observation.
PMID- 24349014
TI - Patients' & healthcare professionals' values regarding true- & false-positive
diagnosis when colorectal cancer screening by CT colonography: discrete choice
experiment.
AB - PURPOSE: To establish the relative weighting given by patients and healthcare
professionals to gains in diagnostic sensitivity versus loss of specificity when
using CT colonography (CTC) for colorectal cancer screening. MATERIALS AND
METHODS: Following ethical approval and informed consent, 75 patients and 50
healthcare professionals undertook a discrete choice experiment in which they
chose between "standard" CTC and "enhanced" CTC that raised diagnostic
sensitivity 10% for either cancer or polyps in exchange for varying levels of
specificity. We established the relative increase in false-positive diagnoses
participants traded for an increase in true-positive diagnoses. RESULTS: Data
from 122 participants were analysed. There were 30 (25%) non-traders for the
cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in
sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity,
equating to 2250 (IQR 1250 to >4250) additional false-positives per additional
true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5
to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional
true-positive polyp, at 25% prevalence. Tipping points were significantly higher
for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps
(55 vs 15, p<0.001). Patients were willing to pay significantly more for
increased sensitivity for cancer (p = 0.021). CONCLUSION: When screening for
colorectal cancer, patients and professionals believe gains in true-positive
diagnoses are worth much more than the negative consequences of a corresponding
rise in false-positives. Evaluation of screening tests should account for this.
PMID- 24349015
TI - Resource competition may lead to effective treatment of antibiotic resistant
infections.
AB - Drug resistance is a common problem in the fight against infectious diseases.
Recent studies have shown conditions (which we call antiR) that select against
resistant strains. However, no specific drug administration strategies based on
this property exist yet. Here, we mathematically compare growth of resistant
versus sensitive strains under different treatments (no drugs, antibiotic, and
antiR), and show how a precisely timed combination of treatments may help defeat
resistant strains. Our analysis is based on a previously developed model of
infection and immunity in which a costly plasmid confers antibiotic resistance.
As expected, antibiotic treatment increases the frequency of the resistant
strain, while the plasmid cost causes a reduction of resistance in the absence of
antibiotic selection. Our analysis suggests that this reduction occurs under
competition for limited resources. Based on this model, we estimate treatment
schedules that would lead to a complete elimination of both sensitive and
resistant strains. In particular, we derive an analytical expression for the rate
of resistance loss, and hence for the time necessary to turn a resistant
infection into sensitive (tclear). This time depends on the experimentally
measurable rates of pathogen division, growth and plasmid loss. Finally, we
estimated tclear for a specific case, using available empirical data, and found
that resistance may be lost up to 15 times faster under antiR treatment when
compared to a no treatment regime. This strategy may be particularly suitable to
treat chronic infection. Finally, our analysis suggests that accounting
explicitly for a resistance-decaying rate may drastically change predicted
outcomes in host-population models.
PMID- 24349016
TI - Automated identification and location analysis of marked stem cells colonies in
optical microscopy images.
AB - Embryonic stem cells (ESCs) are characterized by two remarkable peculiarities:
the capacity to propagate as undifferentiated cells (self-renewal) and the
ability to differentiate in ectoderm, endoderm, and mesoderm derivatives
(pluripotency). Although the majority of ESCs divide without losing the
pluripotency, it has become evident that ESC cultures consists of multiple cell
populations highlighted by the expression of early germ lineage markers during
spontaneous differentiation. Hence, the identification and characterization of
ESCs subpopulations represents an efficient approach to improve the comprehension
of correlation between gene expression and cell specification status. To study
markers of ESCs heterogeneity, we developed an analysis pipeline which can
automatically process images of stem cell colonies in optical microscopy. The
question we try to address is to find out the statistically significant preferred
locations of the marked cells. We tested our algorithm on a set of images of stem
cell colonies to analyze the expression pattern of the Zscan4 gene, which was an
elite candidate gene to be studied because it is specifically expressed in
subpopulation of ESCs. To validate the proposed method we analyzed the behavior
of control genes whose pattern had been associated to biological status such as
differentiation (EndoA), pluripotency (Pou5f1), and pluripotency fluctuation
(Nanog). We found that Zscan4 is not uniformly expressed inside a stem cell
colony, and that it tends to be expressed towards the center of the colony,
moreover cells expressing Zscan4 cluster each other. This is of significant
importance because it allows us to hypothesize a biological status where the
cells expressing Zscan4 are preferably associated to the inner of colonies
suggesting pluripotent cell status features, and the clustering between
themselves suggests either a colony paracrine effect or an early phase of cell
specification through proliferation. Also, the analysis on the control genes
showed that they behave as expected.
PMID- 24349017
TI - Forgiver triumphs in alternating Prisoner's Dilemma.
AB - Cooperative behavior, where one individual incurs a cost to help another, is a
wide spread phenomenon. Here we study direct reciprocity in the context of the
alternating Prisoner's Dilemma. We consider all strategies that can be
implemented by one and two-state automata. We calculate the payoff matrix of all
pairwise encounters in the presence of noise. We explore deterministic selection
dynamics with and without mutation. Using different error rates and payoff
values, we observe convergence to a small number of distinct equilibria. Two of
them are uncooperative strict Nash equilibria representing always-defect (ALLD)
and Grim. The third equilibrium is mixed and represents a cooperative alliance of
several strategies, dominated by a strategy which we call Forgiver. Forgiver
cooperates whenever the opponent has cooperated; it defects once when the
opponent has defected, but subsequently Forgiver attempts to re-establish
cooperation even if the opponent has defected again. Forgiver is not an
evolutionarily stable strategy, but the alliance, which it rules, is
asymptotically stable. For a wide range of parameter values the most commonly
observed outcome is convergence to the mixed equilibrium, dominated by Forgiver.
Our results show that although forgiving might incur a short-term loss it can
lead to a long-term gain. Forgiveness facilitates stable cooperation in the
presence of exploitation and noise.
PMID- 24349018
TI - The good, the bad, and the ugly: agonistic behaviour in juvenile crocodilians.
AB - We examined agonistic behaviour in seven species of hatchling and juvenile
crocodilians held in small groups (N = 4) under similar laboratory conditions.
Agonistic interactions occurred in all seven species, typically involved two
individuals, were short in duration (5-15 seconds), and occurred between 1600
2200 h in open water. The nature and extent of agonistic interactions, the
behaviours displayed, and the level of conspecific tolerance varied among
species. Discrete postures, non-contact and contact movements are described.
Three of these were species-specific: push downs by C. johnstoni; inflated tail
sweeping by C. novaeguineae; and, side head striking combined with tail wagging
by C. porosus. The two long-snouted species (C. johnstoni and G. gangeticus)
avoided contact involving the head and often raised the head up out of the way
during agonistic interactions. Several behaviours not associated with aggression
are also described, including snout rubbing, raising the head up high while at
rest, and the use of vocalizations. The two most aggressive species (C. porosus,
C. novaeguineae) appeared to form dominance hierarchies, whereas the less
aggressive species did not. Interspecific differences in agonistic behaviour may
reflect evolutionary divergence associated with morphology, ecology, general life
history and responses to interspecific conflict in areas where multiple species
have co-existed. Understanding species-specific traits in agonistic behaviour and
social tolerance has implications for the controlled raising of different species
of hatchlings for conservation, management or production purposes.
PMID- 24349019
TI - Modulatory effects of spectral energy contrasts on lateral inhibition in the
human auditory cortex: an MEG study.
AB - We investigated the modulation of lateral inhibition in the human auditory cortex
by means of magnetoencephalography (MEG). In the first experiment, five acoustic
masking stimuli (MS), consisting of noise passing through a digital notch filter
which was centered at 1 kHz, were presented. The spectral energy contrasts of
four MS were modified systematically by either amplifying or attenuating the edge
frequency bands around the notch (EFB) by 30 dB. Additionally, the width of EFB
amplification/attenuation was varied (3/8 or 7/8 octave on each side of the
notch). N1m and auditory steady state responses (ASSR), evoked by a test stimulus
with a carrier frequency of 1 kHz, were evaluated. A consistent dependence of N1m
responses upon the preceding MS was observed. The minimal N1m source strength was
found in the narrowest amplified EFB condition, representing pronounced lateral
inhibition of neurons with characteristic frequencies corresponding to the center
frequency of the notch (NOTCH CF) in secondary auditory cortical areas. We tested
in a second experiment whether an even narrower bandwidth of EFB amplification
would result in further enhanced lateral inhibition of the NOTCH CF. Here three
MS were presented, two of which were modified by amplifying 1/8 or 1/24 octave
EFB width around the notch. We found that N1m responses were again significantly
smaller in both amplified EFB conditions as compared to the NFN condition. To our
knowledge, this is the first study demonstrating that the energy and width of the
EFB around the notch modulate lateral inhibition in human secondary auditory
cortical areas. Because it is assumed that chronic tinnitus is caused by a lack
of lateral inhibition, these new insights could be used as a tool for further
improvement of tinnitus treatments focusing on the lateral inhibition of neurons
corresponding to the tinnitus frequency, such as the tailor-made notched music
training.
PMID- 24349021
TI - Analysis of the spatial organization of molecules with robust statistics.
AB - One major question in molecular biology is whether the spatial distribution of
observed molecules is random or organized in clusters. Indeed, this analysis
gives information about molecules' interactions and physical interplay with their
environment. The standard tool for analyzing molecules' distribution
statistically is the Ripley's K function, which tests spatial randomness through
the computation of its critical quantiles. However, quantiles' computation is
very cumbersome, hindering its use. Here, we present an analytical expression of
these quantiles, leading to a fast and robust statistical test, and we derive the
characteristic clusters' size from the maxima of the Ripley's K function.
Subsequently, we analyze the spatial organization of endocytic spots at the cell
membrane and we report that clathrin spots are randomly distributed while
clathrin-independent spots are organized in clusters with a radius of 2 MUm,
which suggests distinct physical mechanisms and cellular functions for each
pathway.
PMID- 24349020
TI - Increased firing irregularity as an emergent property of neural-state transition
in monkey prefrontal cortex.
AB - Flexible behaviors are organized by complex neural networks in the prefrontal
cortex. Recent studies have suggested that such networks exhibit multiple
dynamical states, and can switch rapidly from one state to another. In many
complex systems such as the brain, the early-warning signals that may predict
whether a critical threshold for state transitions is approaching are extremely
difficult to detect. We hypothesized that increases in firing irregularity are a
crucial measure for predicting state transitions in the underlying neuronal
circuits of the prefrontal cortex. We used both experimental and theoretical
approaches to test this hypothesis. Experimentally, we analyzed activities of
neurons in the prefrontal cortex while monkeys performed a maze task that
required them to perform actions to reach a goal. We observed increased firing
irregularity before the activity changed to encode goal-to-action information.
Theoretically, we constructed theoretical generic neural networks and
demonstrated that changes in neuronal gain on functional connectivity resulted in
a loss of stability and an altered state of the networks, accompanied by
increased firing irregularity. These results suggest that assessing the temporal
pattern of neuronal fluctuations provides important clues regarding the state
stability of the prefrontal network. We also introduce a novel scheme that the
prefrontal cortex functions in a metastable state near the critical point of
bifurcation. According to this scheme, firing irregularity in the prefrontal
cortex indicates that the system is about to change its state and the flow of
information in a flexible manner, which is essential for executive functions.
This metastable and/or critical dynamical state of the prefrontal cortex may
account for distractibility and loss of flexibility in the prefrontal cortex in
major mental illnesses such as schizophrenia.
PMID- 24349022
TI - Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively
modulate GABA mediated neurotransmission to delay onset of seizures.
AB - In the brain, seizures lead to release of large amounts of polyunsaturated fatty
acids including arachidonic acid (ARA). ARA is a substrate for three major
enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome
P450 enzymes. These enzymes convert ARA to potent lipid mediators including
prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids
and leukotrienes are largely pro-inflammatory molecules that sensitize neurons
whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent
evidence suggests a GABA-related mode of action potentially mediated by
neurosteroids. Here we tested this hypothesis using models of chemically induced
seizures. The level of EETs in the brain was modulated by inhibiting the soluble
epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive
molecules, by genetic deletion of sEH and by direct administration of EETs into
the brain. All three approaches delayed onset of seizures instigated by GABA
antagonists but not seizures through other mechanisms. Inhibition of neurosteroid
synthesis by finasteride partially blocked the anticonvulsant effects of sEH
inhibitors while the efficacy of an inactive dose of neurosteroid
allopregnanolone was enhanced by sEH inhibition. Consistent with earlier
findings, levels of prostanoids in the brain were elevated. In contrast, levels
of bioactive EpFAs were decreased following seizures. Overall these results
demonstrate that EETs are natural molecules which suppress the tonic component of
seizure related excitability through modulating the GABA activity and that
exploration of the EET mediated signaling in the brain could yield alternative
approaches to treat convulsive disorders.
PMID- 24349023
TI - Ubiquitin-specific peptidase 5, a target molecule of vialinin A, is a key
molecule of TNF-alpha production in RBL-2H3 cells.
AB - Tumor necrosis factor alpha (TNF-alpha), a central mediator of the inflammatory
response, is released from basophilic cells and other cells in response to a
variety of proinflammatory stimuli. Vialinin A is a potent inhibitor of TNF-alpha
production and is released from RBL-2H3 cells. Ubiquitin-specific peptidase 5
(USP5), a deubiquitinating enzyme, was identified as a target molecule of
vialinin A and its enzymatic activity was inhibited by vialinin A. Here we report
production of TNF-alpha is decreased in USP5 siRNA-knockdown RBL-2H3 cells,
compared with control cells. The finding of the present study strongly suggests
that USP5 is one of the essential molecules for the production of TNF-alpha in
RBL-2H3.
PMID- 24349024
TI - Lanternfish (Myctophidae) zoogeography off eastern Australia: a comparison with
physicochemical biogeography.
AB - In this first attempt to model the distributions of a mesopelagic fish family at
this scale in the eastern Australian region (10 degrees S to 57 degrees S),
lanternfish species occurrence data spanning a period from 1928 to 2010 were
modelled against environmental covariates. This involved: (1) data collation and
taxonomic quality checking, (2) classification of trawls into "horizontal"
(presence-absence) and "oblique" (presence-only) types, and classification of
vertical migration patterns using existing literature and the species occurrence
database, (3) binomial GAMs using presence-absence data for representative
temperate, subtropical and tropical species to examine depth interactions with
environmental covariates and refine the selection of environmental layers for
presence-only MAXENT models, (4) Presence-only MAXENT modelling using data from
all trawls and the reduced environmental layers, and (5) Multivariate analysis
(area-wise and species-wise) of the resulting matrix of logistic score by
geographic pixel. We test the hypothesis that major fronts in the region (Tasman
Front, Subtropical Convergence, Subantarctic Front) represent zoogeographic
boundaries. A four-region zoogeographic scheme is hypothesised: Coral Sea region,
Subtropical Lower Water region, Subtropical Convergence/South Tasman region and
Subantarctic region. The Tasman Front, Subtropical Convergence and Subantarctic
Front represented zoogeographic boundaries. An additional boundary at ~25 degrees
S (coined the 'Capricorn' boundary) was adopted to delineate the Coral Sea from
Subtropical Lower Water regions. Lanternfish zoogeographic regions are congruent
with some aspects of two prevailing physicochemical biogeographic schema in the
region, but neither of these schema alone accurately predicts lanternfish
distributions. As lanternfishes integrate vertical ocean processes, the
hypothesised lanternfish zoogeography may represent a useful model for a
generalised pelagic biogeography that should be tested for other oceanic groups.
PMID- 24349026
TI - Fluctuation analysis: can estimates be trusted?
AB - The estimation of mutation rates and relative fitnesses in fluctuation analysis
is based on the unrealistic hypothesis that the single-cell times to division are
exponentially distributed. Using the classical Luria-Delbruck distribution
outside its modelling hypotheses induces an important bias on the estimation of
the relative fitness. The model is extended here to any division time
distribution. Mutant counts follow a generalization of the Luria-Delbruck
distribution, which depends on the mean number of mutations, the relative fitness
of normal cells compared to mutants, and the division time distribution of mutant
cells. Empirical probability generating function techniques yield precise
estimates both of the mean number of mutations and the relative fitness of normal
cells compared to mutants. In the case where no information is available on the
division time distribution, it is shown that the estimation procedure using
constant division times yields more reliable results. Numerical results both on
observed and simulated data are reported.
PMID- 24349025
TI - Family poverty affects the rate of human infant brain growth.
AB - Living in poverty places children at very high risk for problems across a variety
of domains, including schooling, behavioral regulation, and health. Aspects of
cognitive functioning, such as information processing, may underlie these kinds
of problems. How might poverty affect the brain functions underlying these
cognitive processes? Here, we address this question by observing and analyzing
repeated measures of brain development of young children between five months and
four years of age from economically diverse backgrounds (n = 77). In doing so, we
have the opportunity to observe changes in brain growth as children begin to
experience the effects of poverty. These children underwent MRI scanning, with
subjects completing between 1 and 7 scans longitudinally. Two hundred and three
MRI scans were divided into different tissue types using a novel image processing
algorithm specifically designed to analyze brain data from young infants. Total
gray, white, and cerebral (summation of total gray and white matter) volumes were
examined along with volumes of the frontal, parietal, temporal, and occipital
lobes. Infants from low-income families had lower volumes of gray matter, tissue
critical for processing of information and execution of actions. These
differences were found for both the frontal and parietal lobes. No differences
were detected in white matter, temporal lobe volumes, or occipital lobe volumes.
In addition, differences in brain growth were found to vary with socioeconomic
status (SES), with children from lower-income households having slower
trajectories of growth during infancy and early childhood. Volumetric differences
were associated with the emergence of disruptive behavioral problems.
PMID- 24349028
TI - Oculomotor examination of the weapon focus effect: does a gun automatically
engage visual attention?
AB - BACKGROUND: A person is less likely to be accurately remembered if they appear in
a visual scene with a gun, a result that has been termed the weapon focus effect
(WFE). Explanations of the WFE argue that weapons engage attention because they
are unusual and/or threatening, which causes encoding deficits for the other
items in the visual scene. Previous WFE research has always embedded the weapon
and nonweapon objects within a larger context that provides information about an
actor's intention to use the object. As such, it is currently unknown whether a
gun automatically engages attention to a greater extent than other objects
independent of the context in which it is presented. METHOD: Reflexive responding
to a gun compared to other objects was examined in two experiments. Experiment 1
employed a prosaccade gap-overlap paradigm, whereby participants looked toward a
peripheral target, and Experiment 2 employed an antisaccade gap-overlap paradigm,
whereby participants looked away from a peripheral target. In both experiments,
the peripheral target was a gun or a nonthreatening object (i.e., a tomato or
pocket watch). We also controlled how unexpected the targets were and compared
saccadic reaction times across types of objects. RESULTS: A gun was not found to
differentially engage attention compared to the unexpected object (i.e., a pocket
watch). Some evidence was found (Experiment 2) that both the gun and the
unexpected object engaged attention to a greater extent compared the expected
object (i.e., a tomato). CONCLUSION: An image of a gun did not engage attention
to a larger extent than images of other types of objects (i.e., a pocket watch or
tomato). The results suggest that context may be an important determinant of WFE.
The extent to which an object is threatening may depend on the larger context in
which it is presented.
PMID- 24349027
TI - In vivo pharmacological evaluations of novel olanzapine analogues in rats: a
potential new avenue for the treatment of schizophrenia.
AB - Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used
for treating schizophrenia. Unfortunately, Olz administration is associated with
severe weight gain and metabolic disturbances. Both patients and clinicians are
highly interested in the development of new antipsychotics which are as effective
as atypical antipsychotics but which have a lower propensity to induce metabolic
side effects. In the present study, we examined two new derivatives of Olz; OlzEt
(2-ethyl-4-(4'-methylpiperazin-1'-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine),
and OlzHomo (2-ethyl-4-(4'-methyl-1',4'-diazepan-1'-yl)-10H-benzo[b]thieno[2,3-e]
[1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain
and metabolic changes were measured in female Sprague Dawley rats. Animals were
treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day), or vehicle (n = 8),
three times daily at eight-hour intervals for 5 weeks. Furthermore, a
phencyclidine (PCP)-treated rat model was used to examine the prevention of PCP
induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague
Dawley rats were pre-treated with a single dose (3 mg/kg/day) of Olz, OlzEt,
OlzHomo, or vehicle (n = 12), for 2 weeks. Locomotor activity was recorded
following a subcutaneous injection with either saline or PCP (10 mg/kg). Olz was
found to induce weight gain, hyperphagia, visceral fat accumulation, and
metabolic changes associated with reduced histamatergic H1 receptor density in
the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented
promising antipsychotic effects, which did not induce weight gain or fat
deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate
PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo
showed a lower propensity to inhibit these stereotyped behaviours. Our data
suggest that the therapeutic effectiveness of OlzHomo may be delivered at a
higher dose than that of Olz and OlzEt. Overall, OlzEt and OlzHomo may offer a
better pharmacological profile than Olz for treating patients with schizophrenia.
Clinical trials are needed to test this hypothesis.
PMID- 24349029
TI - Optimal caliper width for propensity score matching of three treatment groups: a
Monte Carlo study.
AB - Propensity score matching is a method to reduce bias in non-randomized and
observational studies. Propensity score matching is mainly applied to two
treatment groups rather than multiple treatment groups, because some key issues
affecting its application to multiple treatment groups remain unsolved, such as
the matching distance, the assessment of balance in baseline variables, and the
choice of optimal caliper width. The primary objective of this study was to
compare propensity score matching methods using different calipers and to choose
the optimal caliper width for use with three treatment groups. The authors used
caliper widths from 0.1 to 0.8 of the pooled standard deviation of the logit of
the propensity score, in increments of 0.1. The balance in baseline variables was
assessed by standardized difference. The matching ratio, relative bias, and mean
squared error (MSE) of the estimate between groups in different propensity score
matched samples were also reported. The results of Monte Carlo simulations
indicate that matching using a caliper width of 0.2 of the pooled standard
deviation of the logit of the propensity score affords superior performance in
the estimation of treatment effects. This study provides practical solutions for
the application of propensity score matching of three treatment groups.
PMID- 24349030
TI - A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar
disorder.
AB - BACKGROUND: Impairments in cognitive functions are common in patients suffering
from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive
traits have been proposed as useful for understanding the biological and genetic
mechanisms implicated in cognitive function in healthy individuals and in the
dysfunction observed in psychiatric disorders. METHODS: Sets of genes associated
with a range of cognitive functions often impaired in schizophrenia and bipolar
disorder were generated from a genome-wide association study (GWAS) on a sample
comprising 670 healthy Norwegian adults who were phenotyped for a broad battery
of cognitive tests. These gene sets were then tested for enrichment of
association in GWASs of schizophrenia and bipolar disorder. The GWAS data was
derived from three independent single-centre schizophrenia samples, three
independent single-centre bipolar disorder samples, and the multi-centre
schizophrenia and bipolar disorder samples from the Psychiatric Genomics
Consortium. RESULTS: The strongest enrichments were observed for visuospatial
attention and verbal abilities sets in bipolar disorder. Delayed verbal memory
was also enriched in one sample of bipolar disorder. For schizophrenia, the
strongest evidence of enrichment was observed for the sets of genes associated
with performance in a colour-word interference test and for sets associated with
memory learning slope. CONCLUSIONS: Our results are consistent with the
increasing evidence that cognitive functions share genetic factors with
schizophrenia and bipolar disorder. Our data provides evidence that genetic
studies using polygenic and pleiotropic models can be used to link specific
cognitive functions with psychiatric disorders.
PMID- 24349031
TI - Immunization of Chlamydia pneumoniae (Cpn)-infected Apob(tm2Sgy)Ldlr(tm1Her)/J
mice with a combined peptide of Cpn significantly reduces atherosclerotic lesion
development.
AB - OBJECTIVE: To investigate the antigenic effect of a peptide containing two
epitopes of Chlamydia pneumoniae (Cpn) on atherosclerotic lesion formation in
mice infected with Cpn. MATERIALS AND METHODS: Six-week-old
Apob(tm2Sgy)Ldlr(tm1Her)/J mice were immunized using a repetitive immunization
multiple-sites strategy with KLH-conjugated peptides derived from the major outer
membrane protein and the putative outer membrane protein 5 of Cpn. Mice were fed
a high-fat diet and infected with Cpn twice during the 10-week diet period.
Lesions were evaluated histologically; local and systemic immune responses were
analyzed by immunohistochemistry of aorta samples and cytokine measurements in
plasma samples and splenocyte supernatants. RESULTS: Mice immunized with the
combined Cpn peptide showed a greater reduction in lesion size compared to mice
immunized with either epitope alone [54.7% vs 39.8% or 41.72%] and was also
associated with a significant decrease in lesion area in descending aortas
compared with those in controls (88.9% for combined Cpn peptide, 81.9% for MOMP
peptide and 75.7% for Omp5, respectively). This effect was associated with a
shift in the cellular composition of plaques towards decreased inflammatory cell
and increased regulatory T-cell content. Additionally, the effect was also
connected with decreased secretion of proinflammatory cytokines and increased
production of anti-inflammatory cytokines demonstrated in plasma and in
supernatant on stimulated spleen cells. CONCLUSIONS: Atherosclerotic lesion
formation may be promoted by Cpn infection in the presence of a high-fat diet,
and reduced by immunization with the combined Cpn peptide. The combined peptide
has more potential than either epitope alone in reducing atherosclerotic lesion
development through Treg expansion.
PMID- 24349032
TI - Structure of a highly conserved domain of Rock1 required for Shroom-mediated
regulation of cell morphology.
AB - Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a
well-defined determinant of actin organization and dynamics in most animal cells
characterized to date. One of the primary effectors of Rock is non-muscle myosin
II. Activation of Rock results in increased contractility of myosin II and
subsequent changes in actin architecture and cell morphology. The regulation of
Rock is thought to occur via autoinhibition of the kinase domain via
intramolecular interactions between the N-terminus and the C-terminus of the
kinase. This autoinhibited state can be relieved via proteolytic cleavage,
binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding
of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has
identified the Shroom family of proteins as an additional regulator of Rock
either at the level of cellular distribution or catalytic activity or both. The
Shroom-Rock complex is conserved in most animals and is essential for the
formation of the neural tube, eye, and gut in vertebrates. To address the
mechanism by which Shroom and Rock interact, we have solved the structure of the
coiled-coil region of Rock that binds to Shroom proteins. Consistent with other
observations, the Shroom binding domain is a parallel coiled-coil dimer. Using
biochemical approaches, we have identified a large patch of residues that
contribute to Shrm binding. Their orientation suggests that there may be two
independent Shrm binding sites on opposing faces of the coiled-coil region of
Rock. Finally, we show that the binding surface is essential for Rock
colocalization with Shroom and for Shroom-mediated changes in cell morphology.
PMID- 24349034
TI - Patterns of Saccharina latissima recruitment.
AB - The lack of recovery in Norwegian populations of the kelp Saccharina latissima
(Linnaeus) C. E. Lane, C. Mayes, Druehl & G. W. Saunders after a large-scale
disturbance that occurred sometime between the late 1990s and early 2000s has
raised considerable concerns. Kelp forests are areas of high production that
serve as habitats for numerous species, and their continued absence may represent
the loss of an entire ecosystem. Some S. latissima populations remain as
scattered patches within the affected areas, but today, most of the areas are
completely devoid of kelp. The question is if natural recolonization by kelp and
the reestablishment of the associated ecosystem is possible. Previous studies
indicate that a high degree of reproductive synchrony in macrophytes has a
positive effect on their potential for dispersal and on the connectivity between
populations, but little is known about the patterns of recruitment in Norwegian
S. latissima. More is, however, known about the development of fertile tissue
(sori) on adult individuals, which is easily observed. The present study
investigated the degree of coupling between the appearance of sori and the
recruitment on clean artificial substrate beneath adult specimens. The pattern of
recruitment was linked to the retreat of visible sori (i.e. spore release) and a
seasonal component unrelated to the fertility of the adults. The formation and
the retreat of visible sori are processes that seem synchronized along the south
coast of Norway, and the link between sori development and recruitment may
therefore suggest that the potential for S. latissima dispersal is relatively
large. These results support the notion that the production and dispersal of
viable spores is unlikely to be the bottleneck preventing recolonization in the
south of Norway, but studies over larger temporal and spatial scales are still
needed to confirm this hypothesis.
PMID- 24349033
TI - Screening and identification of six serum microRNAs as novel potential
combination biomarkers for pulmonary tuberculosis diagnosis.
AB - BACKGROUND: It is very difficult to prevent pulmonary tuberculosis (TB) due to
the lack of specific and diagnostic markers, which could lead to a high incidence
of pulmonary TB. We screened the differentially expressed serum microRNAs
(miRNAs) as potential biomarkers for the diagnosis of pulmonary TB. METHODS: In
this study, serum miRNAs were screened using the Solexa sequencing method as the
potential biomarkers for the diagnosis of pulmonary TB. The stem-loop
quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was
used to verify differentially expressed serum miRNAs. The receiver operating
characteristic (ROC) curve and logistic regression model were used to analyze the
sensitivity and specificity of the single miRNA and a combination of miRNAs for
diagnosis, respectively. Using the predicted target genes, we constructed the
regulatory networks of miRNAs and genes that were related to pulmonary TB.
RESULTS: The Solexa sequencing data showed that 91 serum miRNAs were
differentially expressed in pulmonary TB patients, compared to healthy controls.
Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p,
hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant
difference among pulmonary TB patients, healthy controls (P<0.001) and
differential diagnosis groups (including patients with pneumonia, lung cancer and
chronic obstructive pulmonary disease) (P<0.05). The logistic regression analysis
of a combination of six serum miRNAs revealed that the sensitivity and the
specificity of TB diagnosis were 95.0% and 91.8% respectively. The miRNAs-gene
regulatory networks revealed that several miRNAs may regulate some target genes
involved in immune pathways and participate in the pathogenesis of pulmonary TB.
CONCLUSION: Our study suggests that a combination of six serum miRNAs have great
potential to serve as non-invasive biomarkers of pulmonary TB.
PMID- 24349035
TI - Predicting protein-protein interaction by the mirrortree method: possibilities
and limitations.
AB - Molecular co-evolution analysis as a sequence-only based method has been used to
predict protein-protein interactions. In co-evolution analysis, Pearson's
correlation within the mirrortree method is a well-known way of quantifying the
correlation between protein pairs. Here we studied the mirrortree method on both
known interacting protein pairs and sets of presumed non-interacting protein
pairs, to evaluate the utility of this correlation analysis method for predicting
protein-protein interactions within eukaryotes. We varied metrics for computing
evolutionary distance and evolutionary span of the species analyzed. We found the
differences between co-evolutionary correlation scores of the interacting and non
interacting proteins, normalized for evolutionary span, to be significantly
predictive for proteins conserved over a wide range of eukaryotic clades (from
mammals to fungi). On the other hand, for narrower ranges of evolutionary span,
the predictive power was much weaker.
PMID- 24349036
TI - Unhealthy days and quality of life in Irish patients with diabetes.
AB - OBJECTIVES: To study the determinants of health-related quality of life (HRQoL)
in Irish patients with diabetes using the Centres for Disease Controls' (CDC's)
'Unhealthy Days' summary measure and to assesses the agreement between this
generic HRQoL measure and the disease-specific Audit of Diabetes Dependant
Quality of Life (ADDQoL) measure. RESEARCH DESIGN AND METHODS: Data were analysed
from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people
with diabetes in Ireland (71% response rate). Unhealthy days were assessed using
the CDC's 'Unhealthy days' summary measure. Quality of life (QoL) was also
assessed using the ADDQoL measure. Analyses were conducted primarily using
logistic regression. The agreement between the two QoL instruments was measured
using the kappa co-efficient. RESULTS: Participants reported a median of 2
unhealthy days per month. In multivariate analyses, female gender (P = 0.001),
insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly
associated with more unhealthy days. Older patients had fewer unhealthy days per
month (P = 0.003). Agreement between the two measures of QoL (unhealthy days
measure and ADDQoL) was poor, Kappa = 0.234. CONCLUSIONS: The findings highlight
the determinants of HRQoL in patients with diabetes using a generic HRQoL summary
measure. The 'Unhealthy Days' and the ADDQoL have poor agreement, therefore the
'Unhealthy Days' summary measure may be assessing a different construct.
Nonetheless, this study demonstrates that the generic 'Unhealthy Days' summary
measure can be used to detect determinants of HRQoL in patients with diabetes.
PMID- 24349037
TI - Curcumin intake affects miRNA signature in murine melanoma with mmu-miR-205-5p
most significantly altered.
AB - Melanoma is the most aggressive form of skin cancer with estimated 48,000 deaths
per year worldwide. The polyphenol curcumin derived from the plant Curcuma longa
is well known for its anti-inflammatory and anti-cancerogenic properties.
Accordingly, dietary intake of this compound may be suitable for melanoma
prevention. However, how this compound affects basic cellular mechanisms in
developing melanoma still remains elusive. Therefore, the aim of this study was
to investigate for the first time the impact of oral curcumin administration on
the miRNA signature of engrafting melanoma. For this purpose, the effects of a 4%
curcumin diet were tested on melanoma, which were established by injection of
murine B78H1 cells in the flank of C57BL/6 mice. Curcumin diet or standard chow
(control) was administered two weeks prior to injection of tumor cells until
termination of the experiment. High throughput chip-based array analysis was
deployed to detect alterations in the miRNA signature of the tumors. Curcumin
treatment significantly reduced the growth of the flank tumors. Furthermore the
miRNA expression signature in tumors was substantially altered by curcumin intake
with mmu-miR-205-5p over 100 times higher expressed when compared to controls.
The expression levels of identified key miRNAs in the tumor samples were
confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). A
comparable expression pattern of these miRNAs was also detected in other curcumin
treated melanoma cell lines under in vitro conditions. Putative targets of
curcumin-induced up-regulated miRNAs were enriched in 'o-glycan biosynthesis',
'endoplasmatic reticulum protein processing' and different cancer-related
pathways. Western Blot analyses revealed that of these targets anti-apoptotic B
cell CLL/lymphoma 2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) were
significantly down-regulated in curcumin-treated tumors. These findings
demonstrate a profound alteration of the miRNA expression signature in engrafting
curcumin-treated melanoma with mmu-miR-205-5p being up-regulated most
significantly.
PMID- 24349038
TI - CT morphometric analysis to determine the anatomical basis for the use of
transpedicular screws during reconstruction and fixations of anterior cervical
vertebrae.
AB - BACKGROUND: Accurate placement of pedicle screw during Anterior Transpedicular
Screw fixation (ATPS) in cervical spine depends on accurate anatomical knowledge
of the vertebrae. However, little is known of the morphometric characteristics of
cervical vertebrae in Chinese population. METHODS: Three-dimensional
reconstructions of CT images were performed for 80 cases. The anatomic data and
screw fixation parameters for ATPS fixation were measured using the Mimics
software. FINDINGS: The overall mean OPW, OPH and PAL ranged from 5.81 to 7.49
mm, 7.77 to 8.69 mm, and 33.40 to 31.13 mm separately, and SPA was 93.54 to
109.36 degrees from C3 to C6, 104.99 degrees at C7, whereas, 49.00 to 32.26
degrees from C4 to C7, 46.79 degrees at C3 (TPA). Dl/rSIP had an increasing trend
away from upper endplate with mean value from 1.87 to 5.83 mm. Dl/rTIP was
located at the lateral portion of the anterior cortex of vertebrae for C3 to C5
and ipsilateral for C6 to C7 with mean value from -2.70 to -3.00 mm, and 0.17 to
3.18 mm. The entrance points for pedicular screw insertion for C3 to C5 and C6 to
C7 were recommended -2~-3 mm and 0-4 mm from the median sagittal plane,
respectively, 1-4 mm and 5-6 mm from the upper endplate, with TPA being 46.79
49.00 degrees and 40.89-32.26 degrees, respectively, and SPA being 93.54-106.69
degrees and 109.36-104.99 degrees, respectively. The pedicle screw insertion
diameter was recommended 3.5 mm (C3 and C4), 4.0 mm (C5 to C7), and the pedicle
axial length was 21-24 mm for C3 to C7 for both genders. However, the ATPS
insertion in C3 should be individualized given its relatively small anatomical
dimensions. CONCLUSIONS: The data provided a morphometric basis for the ATPS
fixation technique in lower cervical fixation. It will help in preoperative
planning and execution of this surgery.
PMID- 24349039
TI - Tumor versus stromal cells in culture--survival of the fittest?
AB - Two of the signature genetic events that occur in human gliomas, EGFR
amplification and IDH mutation, are poorly represented in experimental models in
vitro. EGFR amplification, for example, occurs in 40 to 50% of GBM, and yet, EGFR
amplification is rarely preserved in cell cultures derived from human tumors. To
analyze the fate of EGFR amplified and IDH mutated cells in culture, we followed
the development over time of cultures derived from human xenografts in nude rats
enriched for tumor cells with EGFR amplification and of cultures derived from
patient samples with IDH mutations, in serum monolayer and spheroid suspension
culture, under serum and serum free conditions. We observed under serum monolayer
conditions, that nestin positive or nestin and SMA double positive rat stromal
cells outgrew EGFR amplified tumor cells, while serum spheroid cultures preserved
tumor cells with EGFR amplification. Serum free suspension culture exhibited a
more variable cell composition in that the resultant cell populations were either
predominantly nestin/SOX2 co-expressing rat stromal cells or human tumor cells,
or a mixture of both. The selection for nestin/SMA positive stromal cells under
serum monolayer conditions was also consistently observed in human
oligodendrogliomas and oligoastrocytomas with IDH mutations. Our results
highlight for the first time that serum monolayer conditions can select for
stromal cells instead of tumor cells in certain brain tumor subtypes. This result
has an important impact on the establishment of new tumor cell cultures from
brain tumors and raises the question of the proper conditions for the growth of
the tumor cell populations of interest.
PMID- 24349040
TI - Complex variation in measures of general intelligence and cognitive change.
AB - Combining information from multiple SNPs may capture a greater amount of genetic
variation than from the sum of individual SNP effects and help identifying
missing heritability. Regions may capture variation from multiple common variants
of small effect, multiple rare variants or a combination of both. We describe
regional heritability mapping of human cognition. Measures of crystallised (gc)
and fluid intelligence (gf) in late adulthood (64-79 years) were available for
1806 individuals genotyped for 549,692 autosomal single nucleotide polymorphisms
(SNPs). The same individuals were tested at age 11, enabling us the rare
opportunity to measure cognitive change across most of their lifespan. 547,750
SNPs ranked by position are divided into 10, 908 overlapping regions of 101 SNPs
to estimate the genetic variance each region explains, an approach that resembles
classical linkage methods. We also estimate the genetic variation explained by
individual autosomes and by SNPs within genes. Empirical significance thresholds
are estimated separately for each trait from whole genome scans of 500 permutated
data sets. The 5% significance threshold for the likelihood ratio test of a
single region ranged from 17-17.5 for the three traits. This is the equivalent to
nominal significance under the expectation of a chi-squared distribution (between
1 df and 0) of P<1.44*10(-5). These thresholds indicate that the distribution of
the likelihood ratio test from this type of variance component analysis should be
estimated empirically. Furthermore, we show that estimates of variation explained
by these regions can be grossly overestimated. After applying permutation
thresholds, a region for gf on chromosome 5 spanning the PRRC1 gene is
significant at a genome-wide 10% empirical threshold. Analysis of gene
methylation on the temporal cortex provides support for the association of PRRC1
and fluid intelligence (P = 0.004), and provides a prime candidate gene for high
throughput sequencing of these uniquely informative cohorts.
PMID- 24349041
TI - The three subtypes of tick-borne encephalitis virus induce encephalitis in a
natural host, the bank vole (Myodes glareolus).
AB - Tick-borne encephalitis virus (TBEV) infects bank voles (Myodes glareolus) in
nature, but the relevance of rodents for TBEV transmission and maintenance is
unclear. We infected colonized bank voles subcutaneously to study and compare the
infection kinetics, acute infection, and potential viral persistence of the three
known TBEV subtypes: European (TBEV-Eur), Siberian (TBEV-Sib) and Far Eastern
(TBEV-FE). All strains representing the three subtypes were infective and highly
neurotropic. They induced (meningo)encephalitis in some of the animals, however
most of the cases did not present with apparent clinical symptoms. TBEV-RNA was
cleared significantly slower from the brain as compared to other organs studied.
Supporting our earlier findings in natural rodent populations, TBEV-RNA could be
detected in the brain for up to 168 days post infection, but we could not
demonstrate infectivity by cell culture isolation. Throughout all time points
post infection, RNA of the TBEV-FE was detected significantly more often than RNA
of the other two strains in all organs studied. TBEV-FE also induced prolonged
viremia, indicating distinctive kinetics in rodents in comparison to the other
two subtypes. This study shows that bank voles can develop a neuroinvasive TBEV
infection with persistence of viral RNA in brain, and mount an anti-TBEV IgG
response. The findings also provide further evidence that bank voles can serve as
sentinels for TBEV endemicity.
PMID- 24349042
TI - Norisoboldine suppresses VEGF-induced endothelial cell migration via the cAMP-PKA
NF-kappaB/Notch1 pathway.
AB - The migration of endothelial cells has been regarded as a potential target for
the treatment of angiogenesis-related diseases. Previously, we demonstrated that
norisoboldine (NOR), an alkaloid compound isolated from Radix Linderae, can
significantly suppress synovial angiogenesis by selectively inhibiting
endothelial cell migration. In this study, we evaluated the importance of various
pathways in VEGF-induced endothelial cell migration using specific inhibitor.
VEGF-induced endothelial cell migration and sprouting were significantly
inhibited by H-89 (an inhibitor of protein kinase A (PKA)) but not by inhibitors
of other pathways. NOR markedly suppressed VEGF-induced intracytoplasmic cAMP
production and PKA activation and thereby down-regulated the activation of
downstream components of the PKA pathway, including enzymes (src, VASP and eNOS)
and the transcription factor NF-kappaB. Moreover, the transcription activation
potential of NF-kappaB, which is related to IkappaBalpha phosphorylation and the
disruption of the p65/IkappaBalpha complex, was reduced by NOR. Meanwhile, NOR
selectively inhibited the expression of p-p65 (ser276) but not p-p65 (ser536) or
PKAc, indicating that PKAc participates in the regulation of NF-kappaB by NOR. Co
immunoprecipitation and immunofluorescence assays confirmed that NOR inhibited
the formation of the PKAc/p65 complex and thereby decreased p65 (ser276)
phosphorylation to prevent p65 binding to DNA. Docking models indicated that the
affinity of NOR for PKA was higher than that of the original PKA ligand.
Moreover, the fact that H-89 improved Notch1 activation, but DAPT (an inhibitor
of Notch) failed to affect PKA activation, suggested that PKA may act on upstream
of Notch1. In conclusion, the inhibitory effects of NOR on endothelial cell
migration can be attributed to its modulation of the PKA pathway, especially on
the processes of p65/IkappaBalpha complex disruption and PKAc/p65 complex
formation. These results suggest that NOR inhibit VEGF-induced endothelial cell
migration via a cAMP-PKA-NF-kappaB/Notch1 signaling pathway.
PMID- 24349043
TI - Nifedipine treatment reduces resting calcium concentration, oxidative and
apoptotic gene expression, and improves muscle function in dystrophic mdx mice.
AB - Duchenne Muscular Dystrophy (DMD) is a recessive X-linked genetic disease, caused
by mutations in the gene encoding dystrophin. DMD is characterized in humans and
in mdx mice by a severe and progressive destruction of muscle fibers,
inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers,
we have shown that basal ATP release is increased and that extracellular ATP
stimulation is pro-apoptotic. In normal fibers, depolarization-induced ATP
release is blocked by nifedipine, leading us to study the potential therapeutic
effect of nifedipine in mdx muscles and its relation with extracellular ATP
signaling. Acute exposure to nifedipine (10 uM) decreased [Ca(2+)]r, NF-kappaB
activity and iNOS expression in mdx myotubes. In addition, 6-week-old mdx mice
were treated with daily intraperitoneal injections of nifedipine, 1 mg/Kg for 1
week. This treatment lowered the [Ca(2+)]r measured in vivo in the mdx vastus
lateralis. We demonstrated that extracellular ATP levels were higher in adult mdx
flexor digitorum brevis (FDB) fibers and can be significantly reduced after 1
week of treatment with nifedipine. Interestingly, acute treatment of mdx FDB
fibers with apyrase, an enzyme that completely degrades extracellular ATP to AMP,
reduced [Ca(2+)]r to a similar extent as was seen in FDB fibers after 1-week of
nifedipine treatment. Moreover, we demonstrated that nifedipine treatment reduced
mRNA levels of pro-oxidative/nitrosative (iNOS and gp91(phox)/p47(phox) NOX2
subunits) and pro-apoptotic (Bax) genes in mdx diaphragm muscles and lowered
serum creatine kinase (CK) levels. In addition, nifedipine treatment increased
muscle strength assessed by the inverted grip-hanging test and exercise tolerance
measured with forced swimming test in mdx mice. We hypothesize that nifedipine
reduces basal ATP release, thereby decreasing purinergic receptor activation,
which in turn reduces [Ca(2+)]r in mdx skeletal muscle cells. The results in this
work open new perspectives towards possible targets for pharmacological
approaches to treat DMD.
PMID- 24349044
TI - Second language as an exemptor from sociocultural norms. Emotion-Related Language
Choice revisited.
AB - Bilinguals often switch languages depending on what they are saying. According to
the Emotion-Related Language Choice theory, they find their second language an
easier medium of conveying content which evokes strong emotions. The first
language carries too much emotional power, which can be threatening for the
speaker. In a covert experiment, bilingual Polish students translated texts
brimming with expletives from Polish into English and vice versa. In the Polish
translations, the swear word equivalents used were weaker than in the source
text; in the English translations, they were stronger than in the original. These
results corroborate the ERLC theory. However, the effect was only observed for
ethnophaulisms, i.e. expletives directed at social groups. It turns out that the
main factor triggering the language choice in bilinguals is not necessarily the
different emotional power of both languages, but social and cultural norms.
PMID- 24349045
TI - Indigenous burning as conservation practice: neotropical savanna recovery amid
agribusiness deforestation in Central Brazil.
AB - International efforts to address climate change by reducing tropical
deforestation increasingly rely on indigenous reserves as conservation units and
indigenous peoples as strategic partners. Considered win-win situations where
global conservation measures also contribute to cultural preservation, such
alliances also frame indigenous peoples in diverse ecological settings with the
responsibility to offset global carbon budgets through fire suppression based on
the presumed positive value of non-alteration of tropical landscapes.
Anthropogenic fire associated with indigenous ceremonial and collective hunting
practices in the Neotropical savannas (cerrado) of Central Brazil is routinely
represented in public and scientific conservation discourse as a cause of
deforestation and increased CO2 emissions despite a lack of supporting evidence.
We evaluate this claim for the Xavante people of Pimentel Barbosa Indigenous
Reserve, Brazil. Building upon 23 years of longitudinal interdisciplinary
research in the area, we used multi-temporal spatial analyses to compare land
cover change under indigenous and agribusiness management over the last four
decades (1973-2010) and quantify the contemporary Xavante burning regime
contributing to observed patterns based on a four year sample at the end of this
sequence (2007-2010). The overall proportion of deforested land remained stable
inside the reserve (0.6%) but increased sharply outside (1.5% to 26.0%).
Vegetation recovery occurred where reserve boundary adjustments transferred lands
previously deforested by agribusiness to indigenous management. Periodic
traditional burning by the Xavante had a large spatial distribution but repeated
burning in consecutive years was restricted. Our results suggest a need to
reassess overreaching conservation narratives about the purported destructiveness
of indigenous anthropogenic fire in the cerrado. The real challenge to
conservation in the fire-adapted cerrado biome is the long-term sustainability of
indigenous lands and other tropical conservation islands increasingly subsumed by
agribusiness expansion rather than the localized subsistence practices of
indigenous and other traditional peoples.
PMID- 24349047
TI - Mother knows best: occurrence and associations of resighted humpback whales
suggest maternally derived fidelity to a Southern Hemisphere coastal feeding
ground.
AB - Site fidelity is common among migratory cetaceans, including humpback whales
(Megaptera novaeangliae). In the Northern Hemisphere it has been found that
fidelity to humpback whale feeding grounds is transferred maternally but this has
never been shown for the species in the Southern Hemisphere. We examined this in
a unique feeding area off west South Africa using resighting data of 68
individually identified humpback whales by means of photographic (tail flukes and
dorsal fins) and/or molecular methods (microsatellite genotyping) over an 18 year
span. We found short-term association patterns and recurrent visits typical of
other feeding grounds. Males and females had different seasonality of attendance.
Significant female-dominated presence corresponded to timing of an expected
influx of females on their southward migration from the breeding ground: firstly
non-nursing (possibly pregnant) females in mid-spring, and mothers and calves in
mid-to late summer. The potential benefit of this mid-latitude feeding area for
females is illustrated by a record of a cow with known age of at least 23 years
that produced calves in three consecutive years, each of which survived to at
least six months of age: the first record of successful post-partum ovulation for
this species in the Southern Hemisphere. We recorded association of a weaned calf
with its mother, and a recurring association between a non-lactating female and
male over more than two years. Moreover, three animals first identified as calves
returned to the same area in subsequent years, sometimes on the same day as their
mothers. This, together with numerous Parent-Offspring relations detected
genetically among and between resighted and non-resighted whales is strongly
suggestive of maternally derived site fidelity at a small spatial scale by a
small sub-population of humpback whales.
PMID- 24349046
TI - Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats
and mice.
AB - Peripheral sensitization during inflammatory pain is mediated by a variety of
endogenous proalgesic mediators including a number of oxidized lipids, some of
which serve endogenous modulators of sensory TRP-channels. These lipids are
eicosanoids of the arachidonic acid and linoleic acid pathway, as well as
lysophophatidic acids (LPAs). However, their regulation pattern during
inflammatory pain and their contribution to peripheral sensitization is still
unclear. Here, we used the UVB-model for inflammatory pain to investigate
alterations of lipid concentrations at the site of inflammation, the dorsal root
ganglia (DRGs) as well as the spinal dorsal horn and quantified 21 lipid species
from five different lipid families at the peak of inflammation 48 hours post
irradiation. We found that known proinflammatory lipids as well as lipids with
unknown roles in inflammatory pain to be strongly increased in the skin, whereas
surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn.
Importantly, although there are profound differences between the number of
cytochrome (CYP) genes between mice and rats, CYP-derived lipids were regulated
similarly in both species. Since TRPV1 agonists such as LPA 18?1, 9- and 13-HODE,
5- and 12-HETE were elevated in the skin, they may contribute to thermal
hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These
results may explain why some studies show relatively weak analgesic effects of
cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not
inhibit synthesis of other proalgesic lipids such as LPA 18?1, 9-and 13-HODE and
HETEs.
PMID- 24349048
TI - Aphotic N2 fixation in the Eastern Tropical South Pacific Ocean.
AB - We examined rates of N2 fixation from the surface to 2000 m depth in the Eastern
Tropical South Pacific (ETSP) during El Nino (2010) and La Nina (2011).
Replicated vertical profiles performed under oxygen-free conditions show that N2
fixation takes place both in euphotic and aphotic waters, with rates reaching 155
to 509 umol N m(-2) d(-1) in 2010 and 24+/-14 to 118+/-87 umol N m(-2) d(-1) in
2011. In the aphotic layers, volumetric N2 fixation rates were relatively low
(<1.00 nmol N L(-1) d(-1)), but when integrated over the whole aphotic layer,
they accounted for 87-90% of total rates (euphotic+aphotic) for the two cruises.
Phylogenetic studies performed in microcosms experiments confirm the presence of
diazotrophs in the deep waters of the Oxygen Minimum Zone (OMZ), which were
comprised of non-cyanobacterial diazotrophs affiliated with nifH clusters 1K
(predominantly comprised of alpha-proteobacteria), 1G (predominantly comprised of
gamma-proteobacteria), and 3 (sulfate reducing genera of the delta-proteobacteria
and Clostridium spp., Vibrio spp.). Organic and inorganic nutrient addition
bioassays revealed that amino acids significantly stimulated N2 fixation in the
core of the OMZ at all stations tested and as did simple carbohydrates at
stations located nearest the coast of Peru/Chile. The episodic supply of these
substrates from upper layers are hypothesized to explain the observed variability
of N2 fixation in the ETSP.
PMID- 24349049
TI - Social environment influences performance in a cognitive task in natural variants
of the foraging gene.
AB - In Drosophila melanogaster, natural genetic variation in the foraging gene
affects the foraging behaviour of larval and adult flies, larval reward learning,
adult visual learning, and adult aversive training tasks. Sitters (for(s)) are
more sedentary and aggregate within food patches whereas rovers (for(R)) have
greater movement within and between food patches, suggesting that these natural
variants are likely to experience different social environments. We hypothesized
that social context would differentially influence rover and sitter behaviour in
a cognitive task. We measured adult rover and sitter performance in a classical
olfactory training test in groups and alone. All flies were reared in groups, but
fly training and testing were done alone and in groups. Sitters trained and
tested in a group had significantly higher learning performances compared to
sitters trained and tested alone. Rovers performed similarly when trained and
tested alone and in a group. In other words, rovers learning ability is
independent of group training and testing. This suggests that sitters may be more
sensitive to the social context than rovers. These differences in learning
performance can be altered by pharmacological manipulations of PKG activity
levels, the foraging (for) gene's gene product. Learning and memory is also
affected by the type of social interaction (being in a group of the same strain
or in a group of a different strain) in rovers, but not in sitters. These results
suggest that for mediates social learning and memory in D. melanogaster.
PMID- 24349050
TI - Observational cohort study of ventricular arrhythmia in adults with Marfan
syndrome caused by FBN1 mutations.
AB - BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk
factors including FBN1 mutation characteristics require elucidation. METHODS AND
RESULTS: We performed an observational cohort study of 80 consecutive adults (30
men, 50 women aged 42+/-15 years) with Marfan syndrome caused by FBN1 mutations.
We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as
>10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets
(Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31+/-18
months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden
cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified
>10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%),
including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N
terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias
related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also
related to increased indexed end-systolic LV diameters (P = .024 and P = .020),
to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged
QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to
mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an
association of VTE with increased NT-proBNP (P<.001) and with mutations in exons
24-32 (P<.001). CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is
associated with an increased risk for arrhythmia, and affected persons may
require life-long monitoring. Ventricular arrhythmia on electrocardiography,
signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors
of VTE.
PMID- 24349051
TI - Experimental differentiation of intraocular masses using ultrahigh-field magnetic
resonance imaging--a case series.
AB - PURPOSE: The case reports presented here were compiled to demonstrate the
potential for improved diagnosis and monitoring of disease progress of
intraocular lesions using ultrahigh-field magnetic resonance microscopy (MRM) at
7.1 Tesla. METHODS: High-resolution ex vivo ocular magnetic resonance (MR) images
were acquired on an ultrahigh-field MR system (7.1 Tesla, ClinScan, Bruker
BioScan, Germany) using a 2-channel coil with 4 coil elements and T2-weighted
turbo spin echo (TSE) sequences of human eyes enucleated because of different
intraocular lesions. Imaging parameters were: 40*40 mm field of view, 512*512
matrix, and 700 um slice thickness. The results were correlated with in vivo
ultrasound and histology of the enucleated eyes. RESULTS: Imaging was performed
in enucleated eyes with choroidal melanoma, malignant melanoma of iris and
ciliary body with scleral perforation, ciliary body melanoma, intraocular
metastasis of esophageal cancer, subretinal bleeding in the presence of
perforated corneal ulcer, hemorrhagic choroidal detachment, and premature
retinopathy with phthisis and ossification of bulbar structures. MR imaging
allowed differentiation between solid and cystic tumor components. In case of
hemorrhage, fluid-fluid levels were identified. Melanin and calcifications caused
significant hypointensity. Microstructural features of eye lesions identified by
MRM were confirmed by histology. CONCLUSION: This study demonstrates the
potential of MRM for the visualization and differential diagnosis of intraocular
lesions. At present, the narrow bore of the magnet still limits the use of this
technology in humans in vivo. Further advances in ultrahigh-field MR imaging will
permit visualization of tumor extent and evaluation of nonclassified intraocular
structures in the near future.
PMID- 24349052
TI - Phase 2a study of ataluren-mediated dystrophin production in patients with
nonsense mutation Duchenne muscular dystrophy.
AB - BACKGROUND: Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have
a nonsense mutation in the dystrophin gene, resulting in a premature stop codon
in the corresponding mRNA and failure to generate a functional protein. Ataluren
(PTC124) enables ribosomal readthrough of premature stop codons, leading to
production of full-length, functional proteins. METHODS: This Phase 2a open
label, sequential dose-ranging trial recruited 38 boys with nonsense mutation
DMD. The first cohort (n = 6) received ataluren three times per day at morning,
midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20) was
dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12) was dosed at 20, 20, 40
mg/kg. Treatment duration was 28 days. Change in full-length dystrophin
expression, as assessed by immunostaining in pre- and post-treatment muscle
biopsy specimens, was the primary endpoint. FINDINGS: Twenty three of 38 (61%)
subjects demonstrated increases in post-treatment dystrophin expression in a
quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative
analysis also showed positive changes in dystrophin expression. Expression was
not associated with nonsense mutation type or exon location. Ataluren trough
plasma concentrations active in the mdx mouse model were consistently achieved at
the mid- and high- dose levels in participants. Ataluren was generally well
tolerated. INTERPRETATION: Ataluren showed activity and safety in this short-term
study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in
a Phase 2b, double-blind, long-term study in nonsense mutation DMD. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00264888.
PMID- 24349054
TI - No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic
cirrhosis in Japanese patients with HCV.
AB - BACKGROUND: Hepatitis C virus (HCV) infection is associated with the development
of cirrhosis and hepatocellular carcinoma and is also related to fatty change of
the liver. Variation in patatin-like phospholipase domain-containing 3 (PNPLA3)
gene is associated with disease progression in nonalcoholic fatty liver disease
(NAFLD). Recent reports have suggested that PNPLA3, IL28B and TLR4-associated
single nucleotide polymorphisms (SNPs) may have an impact on hepatic steatosis or
fibrosis in patients with chronic HCV infection. METHODS AND FINDINGS: Four SNPs
(PNPLA3 rs738409, TLR4 rs4986790, TLR4 rs4986791, IL28B rs8099917) were
identified in Japanese patients infected with HCV. We examined the association
between the distribution of these SNP alleles and fatty change of the liver or
existence of hepatic cirrhosis diagnosed by ultrasonography, one of the widely
accessible and easy-to-use methods. PNPLA3 rs738409 G-allele and IL28B rs 8099917
minor allele were found in 70.0% and 31.1%, respectively. These two TLR4 SNPs
were uniform in Japanese. Fatty change of the liver developed independent of the
abscence of hepatic cirrhosis on sonographic findings and younger age. Hepatic
cirrhosis was associated with a higher aspartate aminotransferase/platelet ratio
index (APRI), no fatty change of the liver, higher BMI and higher AFP levels. No
association between PNPLA3 rs738409/IL28B rs8099917 genotypes and hepatic
steatosis or liver fibrosis was observed. CONCLUSIONS: According to ultrasound
examinations, no association between PNPLA3 rs738409 genotype and fatty change of
the liver or hepatic cirrhosis was found in Japanese patients infected with HCV.
Together, our results suggested that the mechanism of hepatic steatosis
underlying HCV infection might differ from that of NAFLD and should be explored.
PMID- 24349053
TI - Assessing early access to care and child survival during a health system
strengthening intervention in Mali: a repeated cross sectional survey.
AB - BACKGROUND: In 2012, 6.6 million children under age five died worldwide, most
from diseases with known means of prevention and treatment. A delivery gap
persists between well-validated methods for child survival and equitable, timely
access to those methods. We measured early child health care access, morbidity,
and mortality over the course of a health system strengthening model intervention
in Yirimadjo, Mali. The intervention included Community Health Worker active case
finding, user fee removal, infrastructure development, community mobilization,
and prevention programming. METHODS AND FINDINGS: We conducted four household
surveys using a cluster-based, population-weighted sampling methodology at
baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage
of children initiating an effective antimalarial within 24 hours of symptom
onset, the percentage of children reported to be febrile within the previous two
weeks, and the under-five child mortality rate. We compared prevalence of febrile
illness and treatment using chi-square statistics, and estimated and compared
under-five mortality rates using Cox proportional hazard regression. There was a
statistically significant difference in under-five mortality between the 2008 and
2011 surveys; in 2011, the hazard of under-five mortality in the intervention
area was one tenth that of baseline (HR 0.10, p<0.0001). After three years of the
intervention, the prevalence of febrile illness among children under five was
significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p =
0.0009). The percentage of children starting an effective antimalarial within 24
hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p =
0.0195). CONCLUSIONS: Community-based health systems strengthening may facilitate
early access to prevention and care and may provide a means for improving child
survival.
PMID- 24349055
TI - Non-invasive bioluminescence imaging to monitor the immunological control of a
plasmablastic lymphoma-like B cell neoplasia after hematopoietic cell
transplantation.
AB - To promote cancer research and to develop innovative therapies, refined pre
clinical mouse tumor models that mimic the actual disease in humans are of dire
need. A number of neoplasms along the B cell lineage are commonly initiated by a
translocation recombining c-myc with the immunoglobulin heavy-chain gene locus.
The translocation is modeled in the C.129S1-Igha(tm1(Myc)Janz)/J mouse which has
been previously engineered to express c-myc under the control of the endogenous
IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops
diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1
Igha(tm1(Myc)Janz)/J mouse that spontaneously developed a plasmablastic lymphoma
like disease. These cells were cultured, transduced to express eGFP and firefly
luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma
cell line, termed IM380. This model bears several advantages over other models as
it is genetically induced and mimics the translocation that is detectable in a
number of human B cell lymphomas. The growth of the tumor cells, their
dissemination, and response to treatment within immunocompetent hosts can be
imaged non-invasively in vivo due to their expression of firefly luciferase.
IM380 cells are radioresistant in vivo and mice with established tumors can be
allogeneically transplanted to analyze graft-versus-tumor effects of transplanted
T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice
results in prolonged survival. These traits make the IM380 model very valuable
for the study of B cell lymphoma pathophysiology and for the development of
innovative cancer therapies.
PMID- 24349056
TI - CXCL10 gene promoter polymorphism -1447A>G correlates with plasma CXCL10 levels
and is associated with male susceptibility to cerebral malaria.
AB - The risk factors for cerebral malaria (CM) and the wide variation in clinical
manifestations of malaria are poorly understood. Recent studies indicate that
interferon gamma inducible chemokine, CXCL10, is a strong predictor of both human
and experimental cerebral malaria. Increased plasma and cerebrospinal fluid
levels of CXCL10 were tightly associated with fatal CM in Indian and Ghanaian
patients. In the present study, we hypothesized that in a subset of malaria
patients, CM susceptibility is associated with variation in CXCL10 expression. We
determined whether polymorphisms in the CXCL10 gene promoter region played a role
in the clinical status of malaria patients and addressed the genetic basis of
CXCL10 expression during malaria infection. Following extensive bioinformatics
analyses, two reported single nucleotide polymorphisms in the CXCL10 promoter (
135G>A [rs56061981] and -1447A>G [rs4508917]) were identified among 66 CM and 69
non-CM Indian patients using PCR-restriction fragment length polymorphism assay.
Individuals with the -1447(A/G) genotype were susceptible to CM (adjusted odds
ratio [AOR] = 2.60, 95% CI = 1.51-5.85, p = 0.021). In addition, individuals with
the -1447(A/G) genotype had significantly higher plasma CXCL10 levels than
individuals with the -1447(A/A) genotype. Stratifying patients according to
gender, the observed association of CM with over expression of CXCL10 were more
pronounced in males than in female patients (AOR = 5.47, 95% CI = 1.34-22.29, p =
0.018). Furthermore, -135G>A polymorphism conferred a decreased risk of CM among
males (AOR = 0.19, 95% CI = 0.05-0.78, p = 0.021). Polymorphisms in the CXCL10
gene promoter sequence were associated with increased CXCL10 production, which is
linked to severity of CM. These results suggest that the -1447A>G polymorphism in
CXCL10 gene promoter could be partly responsible for the reported variation
underlying severity of CM outcomes particularly in males.
PMID- 24349057
TI - Sperm associated antigen 9 plays an important role in bladder transitional cell
carcinoma.
AB - BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell
carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of
urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9
(SPAG9) in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression
and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines
were assessed for SPAG9 expression. In addition, we investigated the effect of
SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in
UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene
and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC
tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to
be significantly associated with superficial non-muscle invasive stage (P =
0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early
spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of
patients found positive for SPAG9 expression. All four bladder cancer cell lines
revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells
resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and
p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and
CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular
growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS:
Collectively, our data in clinical specimens indicated that SPAG9 is potential
biomarker and therapeutic target for bladder TCC.
PMID- 24349058
TI - Eucommia ulmoides Oliver extract, aucubin, and geniposide enhance lysosomal
activity to regulate ER stress and hepatic lipid accumulation.
AB - Eucommia ulmoides Oliver is a natural product widely used as a dietary supplement
and medicinal plant. Here, we examined the potential regulatory effects of
Eucommia ulmoides Oliver extracts (EUE) on hepatic dyslipidemia and its related
mechanisms by in vitro and in vivo studies. EUE and its two active constituents,
aucubin and geniposide, inhibited palmitate-induced endoplasmic reticulum (ER)
stress, reducing hepatic lipid accumulation through secretion of apolipoprotein B
and associated triglycerides and cholesterol in human HepG2 hepatocytes. To
determine how EUE diminishes the ER stress response, lysosomal and proteasomal
protein degradation activities were analyzed. Although proteasomal activity was
not affected, lysosomal enzyme activities including V-ATPase were significantly
increased by EUE as well as aucubin and geniposide in HepG2 cells. Treatment with
the V-ATPase inhibitor, bafilomycin, reversed the inhibition of ER stress,
secretion of apolipoprotein B, and hepatic lipid accumulation induced by EUE or
its component, aucubin or geniposide. In addition, EUE was determined to regulate
hepatic dyslipidemia by enhancing lysosomal activity and to regulate ER stress in
rats fed a high-fat diet. Together, these results suggest that EUE and its active
components enhance lysosomal activity, resulting in decreased ER stress and
hepatic dyslipidemia.
PMID- 24349059
TI - Exercise protects against diet-induced insulin resistance through downregulation
of protein kinase Cbeta in mice.
AB - Physical exercise is an important and effective therapy for diabetes. However,
its underlying mechanism is not fully understood. Protein kinase Cbeta (PKCbeta)
has been suggested to be involved in the pathogenesis of obesity and insulin
resistance, but the role of PKCbeta in exercise-induced improvements in insulin
resistance is completely unknown. In this study, we evaluated the involvement of
PKCbeta in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed
mice. PKCbeta(-/-) and wild-type mice were fed a HFD with or without exercise
training. PKC protein expression, body and tissue weight change, glucose and
insulin tolerance, metabolic rate, mitochondria size and number, adipose
inflammation, and AKT activation were determined to evaluate insulin sensitivity
and metabolic changes after intervention. PKCbeta expression decreased in both
skeletal muscle and liver tissue after exercise. Exercise and PKCbeta deficiency
can alleviate HFD-induced insulin resistance, as evidenced by improved insulin
tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by
HFD were also ameliorated by both exercise and PKCbeta deficiency. On the other
hand, exercise had little effect on PKCbeta(-/-) mice. Further, our data
indicated improved activation of AKT, the downstream signal molecule of insulin,
in skeletal muscle and liver of exercised mice, whereas PKCbeta deficiency
blunted the difference between sedentary and exercised mice. These results
suggest that downregulation of PKCbeta contributes to exercise-induced
improvement of insulin resistance in HFD-fed mice.
PMID- 24349060
TI - Recovery after work: the role of work beliefs in the unwinding process.
AB - According to the Effort-Recovery model, mental or physical detachment from work
is an important mechanism of work related recovery, as delayed recovery has been
associated with range of negative health symptoms. In this paper, we examine
whether recovery from work (in the form of mentally disengagement from work) is
affected by the concept of 'work ethic', which refers to beliefs workers hold
about their work and leisure and the effects of experiencing interruptions at
work. Two indices of post-work recovery were utilized: problem solving pondering
and psychological detachment. The study was conducted with 310 participants
employed from diverse occupational sectors. Main effects of positive and negative
appraisal of work interruption and beliefs were analysed using mediated and
moderated regression analysis on problem-solving pondering and detachment.
Weakened belief in wasted time as a partial mediator, reduced problem-solving
pondering post work when interruptions were appraised as positive, and a high
evaluation of leisure partially mediated problem-solving pondering when
interruptions were appraised as positive. The results also showed that a high
evaluation of centrality of work and leisure moderated the effect of negative
appraisal of work interruption on elevated problem-solving pondering. Positive
appraisal of work interruption was related to problem-solving pondering, and the
strength of this association was further moderated by a strong belief in delay of
gratification. In addition, employees' positive appraisal of work interruption
was related to work detachment, and the strength of this association was further
moderated by strong beliefs in hard work and self-reliance. These findings are
discussed in terms of their theoretical and practical implications for employees
who are strongly influenced by such work beliefs.
PMID- 24349061
TI - Ex vivo pathomechanics of the canine Pond-Nuki model.
AB - BACKGROUND: Transection of the canine cranial cruciate ligament (CCL) is a well
established osteoarthritis (OA) model. The effect of CCL loss on contact pressure
and joint alignment has not been quantified for stifle loading in standing. The
purposes of the study were to measure femorotibial contact areas and stresses and
joint alignment following transection of the CCL in an ex vivo model. We
hypothesized that transection of the CCL would lead to abnormal kinematics, as
well as alterations in contact mechanics of the femorotibial joint.
METHODOLOGY/PRINCIPAL FINDINGS: Eight canine hindlimbs were tested in a servo
hydraulic materials testing machine using a custom made femoral jig. Contact area
and pressure measurements, and femorotibial rotations and translations were
measured in the normal and the CCL-deficient stifle in both standing and deep
flexion angles. We found that at standing angle, transection of the CCL caused
cranial translation and internal rotation of the tibia with a concurrent caudal
shift of the contact area, an increase in peak pressure and a decrease in contact
area. These changes were not noted in deep flexion. At standing, loss of CCL
caused a redistribution of the joint pressure, with the caudal region of the
compartment being overloaded and the rest of the joint being underloaded.
CONCLUSION: In the Pond-Nuki model alterations in joint alignment are correlated
with shifting of the contact points to infrequently loaded areas of the tibial
plateau. The results of this study suggest that this cadaveric Pond-Nuki model
simulates the biomechanical changes previously reported in the in-vivo Pond-Nuki
model.
PMID- 24349062
TI - Chromosomal characterization of the three subgenomes in the polyploids of Hordeum
murinum L.: new insight into the evolution of this complex.
AB - Hordeum murinum L. is a species complex composed of related taxa, including the
subspecies glaucum, murinum and leporinum. However, the phylogenetic
relationships between the different taxa and their cytotypes, and the origin of
the polyploid forms, remain points of controversy. The present work reports a
comparative karyotype analysis of seven accessions of the H. murinum complex
representing all subspecies and cytotypes. The karyotypes were determined by
examining the distribution of the repetitive Triticeae DNA sequences pTa71,
pTa794, pSc119.2, pAs1 and pHch950, the simple sequence repeats (SSRs) (AG)10,
(AAC)5, (AAG)5, (ACT)5, (ATC)5, and (CCCTAAA)3 via in situ hybridization. The
chromosomes of the three subgenomes involved in the polyploids were identified.
All tetraploids of all subspecies shared the same two subgenomes (thus suggesting
them to in fact belong to the same taxon), the result of hybridization between
two diploid ancestors. One of the subgenomes present in all tetraploids of all
subspecies was found to be very similar (though not identical) to the chromosome
complement of the diploid glaucum. The hexaploid form of leporinum came about
through a cross between a tetraploid and a third diploid form. Exclusively
bivalent associations among homologous chromosomes were observed when analyzing
pollen mother cells of tetraploid taxa. In conclusion, the present results
identify all the individual chromosomes within the H. murinum complex, reveal its
genome structure and phylogeny, and explain the appearance of the different
cytotypes. Three cryptic species are proposed according to ploidy level that may
deserve full taxonomic recognition.
PMID- 24349064
TI - A model of self-organizing head-centered visual responses in primate parietal
areas.
AB - We present a hypothesis for how head-centered visual representations in primate
parietal areas could self-organize through visually-guided learning, and test
this hypothesis using a neural network model. The model consists of a competitive
output layer of neurons that receives afferent synaptic connections from a
population of input neurons with eye position gain modulated retinal receptive
fields. The synaptic connections in the model are trained with an associative
trace learning rule which has the effect of encouraging output neurons to learn
to respond to subsets of input patterns that tend to occur close together in
time. This network architecture and synaptic learning rule is hypothesized to
promote the development of head-centered output neurons during periods of time
when the head remains fixed while the eyes move. This hypothesis is demonstrated
to be feasible, and each of the core model components described is tested and
found to be individually necessary for successful self-organization.
PMID- 24349063
TI - Abnormal organization of white matter network in patients with no dementia after
ischemic stroke.
AB - Structural changes after ischemic stroke could affect information communication
extensively in the brain network. It is likely that the defects in the white
matter (WM) network play a key role in information interchange. In this study, we
used graph theoretical analysis to examine potential organization alteration in
the WM network architecture derived from diffusion tensor images from subjects
with no dementia and experienced stroke in the past 5.4-14.8 months (N = 47, Mini
Mental Screening Examination, MMSE range 18-30), compared with a normal control
group with 44 age and gender-matched healthy volunteers (MMSE range 26-30).
Region-wise connectivity was derived from fiber connection density of 90
different cortical and subcortical parcellations across the whole brain. Both
normal controls and patients with chronic stroke exhibited efficient small-world
properties in their WM structural networks. Compared with normal controls,
topological efficiency was basically unaltered in the patients with chronic
stroke, as reflected by unchanged local and global clustering coefficient,
characteristic path length, and regional efficiency. No significant difference in
hub distribution was found between normal control and patient groups. Patients
with chronic stroke, however, were found to have reduced betweenness centrality
and predominantly located in the orbitofrontal cortex, whereas increased
betweenness centrality and vulnerability were observed in parietal-occipital
cortex. The National Institutes of Health Stroke Scale (NIHSS) score of patient
is correlated with the betweenness centrality of right pallidum and local
clustering coefficient of left superior occipital gyrus. Our findings suggest
that patients with chronic stroke still exhibit efficient small-world
organization and unaltered topological efficiency, with altered topology at
orbitofrontal cortex and parietal-occipital cortex in the overall structural
network. Findings from this study could help in understanding the mechanism of
cognitive impairment and functional compensation occurred in patients with
chronic stroke.
PMID- 24349065
TI - SRComp: short read sequence compression using burstsort and Elias omega coding.
AB - Next-generation sequencing (NGS) technologies permit the rapid production of vast
amounts of data at low cost. Economical data storage and transmission hence
becomes an increasingly important challenge for NGS experiments. In this paper,
we introduce a new non-reference based read sequence compression tool called
SRComp. It works by first employing a fast string-sorting algorithm called
burstsort to sort read sequences in lexicographical order and then Elias omega
based integer coding to encode the sorted read sequences. SRComp has been
benchmarked on four large NGS datasets, where experimental results show that it
can run 5-35 times faster than current state-of-the-art read sequence compression
tools such as BEETL and SCALCE, while retaining comparable compression efficiency
for large collections of short read sequences. SRComp is a read sequence
compression tool that is particularly valuable in certain applications where
compression time is of major concern.
PMID- 24349066
TI - Dispersion estimation and its effect on test performance in RNA-seq data
analysis: a simulation-based comparison of methods.
AB - A central goal of RNA sequencing (RNA-seq) experiments is to detect
differentially expressed genes. In the ubiquitous negative binomial model for RNA
seq data, each gene is given a dispersion parameter, and correctly estimating
these dispersion parameters is vital to detecting differential expression. Since
the dispersions control the variances of the gene counts, underestimation may
lead to false discovery, while overestimation may lower the rate of true
detection. After briefly reviewing several popular dispersion estimation methods,
this article describes a simulation study that compares them in terms of point
estimation and the effect on the performance of tests for differential
expression. The methods that maximize the test performance are the ones that use
a moderate degree of dispersion shrinkage: the DSS, Tagwise wqCML, and Tagwise
APL. In practical RNA-seq data analysis, we recommend using one of these moderate
shrinkage methods with the QLShrink test in QuasiSeq R package.
PMID- 24349067
TI - Preliminary evidence that anodal transcranial direct current stimulation enhances
time to task failure of a sustained submaximal contraction.
AB - The purpose of this study was to determine whether anodal transcranial direct
current stimulation (tDCS) delivered while performing a sustained submaximal
contraction would increase time to task failure (TTF) compared to sham
stimulation. Healthy volunteers (n = 18) performed two fatiguing contractions at
20% of maximum strength with the elbow flexors on separate occasions. During
fatigue task performance, either anodal or sham stimulation was delivered to the
motor cortex for up to 20 minutes. Transcranial magnetic stimulation (TMS) was
used to assess changes in cortical excitability during stimulation. There was no
systematic effect of the anodal tDCS stimulation on TTF for the entire subject
set (n = 18; p = 0.64). Accordingly, a posteriori subjects were divided into two
tDCS-time groups: Full-Time (n = 8), where TTF occurred prior to the termination
of tDCS, and Part-Time (n = 10), where TTF extended after tDCS terminated. The
TTF for the Full-Time group was 31% longer with anodal tDCS compared to sham (p =
0.04), whereas TTF for the Part-Time group did not differ (p = 0.81). Therefore,
the remainder of our analysis addressed the Full-Time group. With anodal tDCS,
the amount of muscle fatigue was 6% greater at task failure (p = 0.05) and the
amount of time the Full-Time group performed the task at an RPE between 8-10
("very hard") increased by 38% (p = 0.04) compared to sham. There was no
difference in measures of cortical excitability between stimulation conditions (p
= 0.90). That the targeted delivery of anodal tDCS during task performance both
increased TTF and the amount of muscle fatigue in a subset of subjects suggests
that augmenting cortical excitability with tDCS enhanced descending drive to the
spinal motorpool to recruit more motor units. The results also suggest that the
application of tDCS during performance of fatiguing activity has the potential to
bolster the capacity to exercise under conditions required to derive benefits due
to overload.
PMID- 24349068
TI - Gene expression analysis of PTEN positive glioblastoma stem cells identifies DUB3
and Wee1 modulation in a cell differentiation model.
AB - The term astrocytoma defines a quite heterogeneous group of neoplastic diseases
that collectively represent the most frequent brain tumors in humans. Among them,
glioblastoma multiforme represents the most malignant form and its associated
prognosis is one of the poorest among tumors of the central nervous system. It
has been demonstrated that a small population of tumor cells, isolated from the
brain neoplastic tissue, can reproduce the parental tumor when transplanted in
immunodeficient mouse. These tumor initiating cells are supposed to be involved
in cancer development and progression and possess stem cell-like features; like
their normal counterpart, these cells remain quiescent until they are committed
to differentiation. Many studies have shown that the role of the tumor suppressor
protein PTEN in cell cycle progression is fundamental for tumor dynamics: in low
grade gliomas, PTEN contributes to maintain cells in G1 while the loss of its
activity is frequently observed in high grade gliomas. The mechanisms underlying
the above described PTEN activity have been studied in many tumors, but those
involved in the maintenance of tumor initiating cells quiescence remain to be
investigated in more detail. The aim of the present study is to shed light on the
role of PTEN pathway on cell cycle regulation in Glioblastoma stem cells, through
a cell differentiation model. Our results suggest the existence of a molecular
mechanism, that involves DUB3 and WEE1 gene products in the regulation of Cdc25a,
as functional effector of the PTEN/Akt pathway.
PMID- 24349069
TI - Confocal comparison of corneal reinnervation after small incision lenticule
extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK).
AB - PURPOSE: To evaluate corneal reinnervation, and the corresponding corneal
sensitivity and keratocyte density after small incision lenticule extraction
(SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: In this
prospective, non-randomized observational study, 18 patients (32 eyes) received
SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct
myopia. The corneal subbasal nerve density and microscopic morphological changes
in corneal architecture were evaluated by confocal microscopy prior to surgery
and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation
analysis was performed between subbasal corneal nerve density and the
corresponding keratocyte density and corneal sensitivity. RESULTS: The decrease
in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK
treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P =
0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The
subbasal nerve density correlated positively with central corneal sensitivity in
both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and
FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of
developing peripheral empty space with epithelial cells filling in (P = 0.0005).
CONCLUSIONS: The decrease in subbasal nerve fiber density was less severe in the
SMILE group than the FS-LASIK group in the first 3 months following the
surgeries. The subbasal nerve density was correlated with central corneal
sensitivity.
PMID- 24349070
TI - Hierarchical self-organization of non-cooperating individuals.
AB - Hierarchy is one of the most conspicuous features of numerous natural,
technological and social systems. The underlying structures are typically complex
and their most relevant organizational principle is the ordering of the ties
among the units they are made of according to a network displaying hierarchical
features. In spite of the abundant presence of hierarchy no quantitative
theoretical interpretation of the origins of a multi-level, knowledge-based
social network exists. Here we introduce an approach which is capable of
reproducing the emergence of a multi-levelled network structure based on the
plausible assumption that the individuals (representing the nodes of the network)
can make the right estimate about the state of their changing environment to a
varying degree. Our model accounts for a fundamental feature of knowledge-based
organizations: the less capable individuals tend to follow those who are better
at solving the problems they all face. We find that relatively simple rules lead
to hierarchical self-organization and the specific structures we obtain possess
the two, perhaps most important features of complex systems: a simultaneous
presence of adaptability and stability. In addition, the performance (success
score) of the emerging networks is significantly higher than the average expected
score of the individuals without letting them copy the decisions of the others.
The results of our calculations are in agreement with a related experiment and
can be useful from the point of designing the optimal conditions for constructing
a given complex social structure as well as understanding the hierarchical
organization of such biological structures of major importance as the regulatory
pathways or the dynamics of neural networks.
PMID- 24349071
TI - The prognostic value of phosphorylated AKT expression in non-small cell lung
cancer: a meta-analysis.
AB - OBJECTIVES: Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a
potentially interesting prognostic marker and therapeutic target in non-small
cell lung cancer (NSCLC). However, the available results of p-AKT expression in
NSCLC are heterogeneous. Therefore, a meta-analysis of published researches
investigating the prognostic relevance of p-AKT expression in patients with NSCLC
was performed. MATERIALS AND METHODS: A literature search via PubMed, EMBASE and
CNKI (China National Knowledge Infrastructure) databases was conducted. Data from
eligible studies were extracted and included into meta-analysis using a random
effects model. RESULTS: A total of 1049 patients from nine studies were included
in the meta-analysis. Nine studies investigated the relationship between p-AKT
expression and overall survival using univariate analysis, and five of these
undertook multivariate analysis. The pooled hazard ratio (HR) for overall
survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate
analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis. CONCLUSION: Our
study shows that positive expression of p-AKT is associated with poor prognosis
in patients with NSCLC. However, adequately designed prospective studies need to
perform.
PMID- 24349073
TI - Estimation of the horizon in photographed outdoor scenes by human and machine.
AB - We present three experiments on horizon estimation. In Experiment 1 we verify the
human ability to estimate the horizon in static images from only visual input.
Estimates are given without time constraints with emphasis on precision. The
resulting estimates are used as baseline to evaluate horizon estimates from early
visual processes. Stimuli are presented for only 153 ms and then masked to purge
visual short-term memory and enforcing estimates to rely on early processes,
only. The high agreement between estimates and the lack of a training effect
shows that enough information about viewpoint is extracted in the first few
hundred milliseconds to make accurate horizon estimation possible. In Experiment
3 we investigate several strategies to estimate the horizon in the computer and
compare human with machine "behavior" for different image manipulations and image
scene types.
PMID- 24349072
TI - Voluntary running in young adult mice reduces anxiety-like behavior and increases
the accumulation of bioactive lipids in the cerebral cortex.
AB - Combinatorial therapies using voluntary exercise and diet supplementation with
polyunsaturated fatty acids have synergistic effects benefiting brain function
and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like
behavior and on total FA accumulation within three brain regions: cortex,
hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J
mice. The running group was subjected to one month of voluntary exercise in their
home cages, while the sedentary group was kept in their home cages without access
to a running wheel. Elevated plus maze (EPM), several behavioral postures and two
risk assessment behaviors (RABs) were then measured in both animal groups
followed immediately by blood samplings for assessment of corticosterone levels.
Brains were then dissected for non-targeted lipidomic analysis of selected brain
regions using gas chromatography coupled to mass spectrometry (GC/MS). Results
showed that mice in the running group, when examined in the EPM, displayed
significantly lower anxiety-like behavior, higher exploratory and risky
behaviors, compared to sedentary mice. Notably, we found no differences in blood
corticosterone levels between the two groups, suggesting that the different EPM
and RAB behaviors were not related to reduced physiological stress in the running
mice. Lipidomics analysis revealed a region-specific cortical decrease of the
saturated FA: palmitate (C16:0) and a concomitant increase of polyunsaturated FA,
arachidonic acid (AA, omega 6-C20: 4) and docosahexaenoic acid (DHA, omega 3-C22:
6), in running mice compared to sedentary controls. Finally, we found that
running mice, as opposed to sedentary animals, showed significantly enhanced
cortical expression of phospholipase A2 (PLA2) protein, a signaling molecule
required in the production of both AA and DHA. In summary, our data support the
anxiolytic effects of exercise and provide insights into the molecular processes
modulated by exercise that may lead to its beneficial effects on mood.
PMID- 24349074
TI - De-etiolation of wheat seedling leaves: cross talk between heme oxygenase/carbon
monoxide and nitric oxide.
AB - Greening of etiolated plants is predominantly stimulated by light but the
complete molecular mechanism is still unknown. Multiple studies currently focus
on the important physiological effects of heme oxygenase (HO)/carbon monoxide
(CO) in plants. In this report, firstly, the role of HO/CO in light-induced de
etiolation process was investigated. We discovered that light could significantly
increase HO activities, HO-1 gene expression, CO release, and chlorophyll
accumulation, all of which were sensitive to zinc protoporphyrin (ZnPPIX), the
potent inhibitor of HO-1, respectively. Both HO-1 inducer hematin (H) and CO
aqueous solution were able to relieve etiolation in wheat seedling leaves under
completely darkness by up-regulating endogenous HO/CO system, so as nitric oxide
(NO) donor sodium nitroprusside (SNP) did. Similarly, endogenous NO production
was also boost in response to light, SNP, hematin and CO aqueous solution in
wheat seedling leaves. Additionally, the restoration of chlorophyll contents was
blocked, when the inhibitor of mammalian nitric oxide synthase N(G)-nitro-L
arginine methylester hydrochloride (L-NAME) or the specific scavenger of NO 2-(4
carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt
(cPTIO) was added, respectively. Furthermore, the inducible effects of light were
different from those of SNP, hematin, and CO on Pfr accumulation and PHYA
transcripts. However, all of sodium nitroprusside (SNP), hematin, and CO could
accelerate NO emission, which suggested that HO/CO in wheat seedlings de
etiolation under dark-light transition may have a cross talk with NO.
PMID- 24349075
TI - Impact of a combined high cholesterol diet and high glucose environment on
vasculature.
AB - AIMS: Vascular complications are the leading cause of mortality and morbidity in
patients with diabetes. However, proper animal models of diabetic vasculopathy
that recapitulate the accelerated progression of vascular lesions in human are
unavailable. In the present study, we developed a zebrafish model of diabetic
vascular complications and the methodology for quantifying vascular lesion
formation real-time in the living diabetic zebrafish. METHODS AND RESULTS: Wild
type zebrafish (AB) and transgenic zebrafish lines of fli1:EGFP, lyz:EGFP,
gata1:dsRed, double transgenic zebrafish of gata1:dsRed/fli1:EGFP were exposed to
high cholesterol diet and 3% glucose (HCD-HG) for 10 days. The zebrafish model
with HCD-HG treatment was characterized by significantly increased tissue levels
of insulin, glucagon, glucose, total triglyceride and cholesterol. Confocal
microscopic analysis further revealed that the diabetic larvae developed clearly
thickened endothelial layers, distinct perivascular lipid depositions,
substantial accumulations of inflammatory cells in the injured vasculature, and a
decreased velocity of blood flow. Moreover, the vascular abnormalities were
improved by the treatment of pioglitazone and metformin. CONCLUSION: A
combination of high cholesterol diet and high glucose exposure induces a rapid
onset of vascular complications in zebrafish similar to the early atherosclerotic
vascular injuries in mammalian diabetic models, suggesting that zebrafish may be
used as a novel animal model for diabetic vasculopathy.
PMID- 24349076
TI - Telomere length correlations among somatic tissues in adult zebra finches.
AB - Telomeres are repetitive non coding DNA sequences located at the end of
eukaryotic chromosomes, which maintain the integrity of the genome by hiding the
chromosome ends from being recognised as double stranded breaks. Telomeres are
emerging as biomarkers for ageing and survival, and are susceptible to reflect
different individual life history trajectories. In particular, the telomere
length with which one starts in life has been shown to be linked with individual
life-long survival, suggesting that telomere dynamics can be a proxy for
individual fitness and thereby be implicated in evolutionary trade-offs. As a
consequence, an increasing number of studies were conducted on telomeres in the
fields of ecology and evolutionary biology, in which telomere length was almost
exclusively measured from blood samples. However, not only do the number of
repeats of the telomeric sequences vary among species, but also within species
with great inter-individual telomere lengths variability with age, tissues, and
chromosomes. This raises the issue of the exact biological meaning of telomere
measurement in blood cells and stimulated the study of the correlation of
telomere lengths among tissues over age. By measuring telomere length in adult
zebra finches (Taeniopygia guttata) in different somatic tissues displaying
variable cell turnovers (bone marrow, brain, spleen, pectoral muscle, heart,
liver and in red blood cells), we checked that the measure of telomere length in
red blood cells is related to telomere lengths in the other tissues. Here we show
significant relationships between the telomere lengths of red blood cells and
several somatic tissues at adulthood. As red blood cells are easily accessible
and suitable for the longitudinal monitoring of the individual rate of telomere
loss, our study confirms that telomere length measured in red blood cells could
serve as a surrogate for telomere length in the whole avian organism.
PMID- 24349077
TI - Serum interleukin-18 levels are associated with physical activity in Japanese
men.
AB - OBJECTIVE: To investigate the link between serum interleukin-18 (IL-18) levels
and physical activity in Japanese men. METHODS: A total of 81 men (45.7+/-17.6
years old) was enrolled in this cross-sectional investigation study. We assessed
anthropometric and body composition parameters. Serum IL-18 levels, physical
activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk
parameters were also evaluated. RESULTS: Serum IL-18 levels were 179.4+/-84.7
pg/mL. Physical activity evaluated by Sigma[metabolic equivalents * h per week
(METs?h/w)]was significantly and negatively correlated with serum IL-18 levels (r
= -0.252, p = 0.0235). These associations remained even after adjusting for age,
peak oxygen uptake and other confounding factors. CONCLUSION: Serum IL-18 levels
were closely associated with physical activity independent of peak oxygen uptake
in Japanese men.
PMID- 24349078
TI - Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT
angiography.
AB - We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in
normal human subjects using optical coherence tomography (OCT). An ultrahigh
speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan
rate is developed for three-dimensional ultrahigh speed imaging of the posterior
eye. OCT angiography is used to image three-dimensional vascular structure
without the need for exogenous fluorophores by detecting erythrocyte motion
contrast between OCT intensity cross-sectional images acquired rapidly and
repeatedly from the same location on the retina. En face OCT angiograms of the
choriocapillaris and choroidal vasculature are visualized by acquiring cross
sectional OCT angiograms volumetrically via raster scanning and segmenting the
three-dimensional angiographic data at multiple depths below the retinal pigment
epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as
tightly packed networks of feeding arterioles and draining venules, can be
visualized at different en face depths. Panoramic ultra-wide field stitched OCT
angiograms of the choriocapillaris spanning ~32 mm on the retina show distinct
vascular structures at different fundus locations. Isolated smaller fields at the
central fovea and ~6 mm nasal to the fovea at the depths of the choriocapillaris
and Sattler's layer show vasculature structures consistent with established
architectural morphology from histological and electron micrograph corrosion
casting studies. Choriocapillaris imaging was performed in eight healthy
volunteers with OCT angiograms successfully acquired from all subjects. These
results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free
choriocapillaris and choroidal vasculature imaging, in addition to conventional
structural imaging.
PMID- 24349079
TI - Detection of tissue factor antigen and coagulation activity in coronary artery
thrombi isolated from patients with ST-segment elevation acute myocardial
infarction.
AB - INTRODUCTION: Although ruptured atherosclerotic plaques have been extensively
analyzed, the composition of thrombi causing arterial occlusion in patients with
ST-segment elevation acute myocardial infarction has been less thoroughly
investigated. We sought to investigate whether coagulant active tissue factor can
be retrieved in thrombi of patients with STEMI undergoing primary percutaneous
coronary intervention. METHODS: Nineteen patients with ST-segment elevation acute
myocardial infarction referred for primary percutaneous coronary intervention
were enrolled in this study. Coronary thrombi aspirated from coronary arteries
were routinely processed for paraffin embedding and histological evaluation (4
patients) or immediately snap frozen for evaluation of tissue factor activity
using a modified aPTT test (15 patients). Immunoprecipitation followed by
immunoblotting was also performed in 12 patients. RESULTS: Thrombi aspirated from
coronary arteries showed large and irregular areas of tissue factor staining
within platelet aggregates, and in close contact with inflammatory cells. Some
platelet aggregates stained positive for tissue factor, whereas others did not.
Monocytes consistently stained strongly for tissue factor, neutrophils had a more
variable and irregular tissue factor staining, and red blood cells did not
demonstrate staining for tissue factor. Median clotting time of plasma samples
containing homogenized thrombi incubated with a monoclonal antibody that
specifically inhibits tissue factor-mediated coagulation activity (mAb 5G9) were
significantly longer than their respective controls (88.9 seconds versus 76.5
seconds, respectively; p<0.001). Tissue factor was also identified by
immunoprecipitation in 10 patients, with significant variability among band
intensities. CONCLUSIONS: Active tissue factor is present in coronary artery
thrombi of patients with ST-segment elevation acute myocardial infarction,
suggesting that it contributes to activate the coagulation cascade ensuing in
coronary thrombosis.
PMID- 24349081
TI - Northern hemisphere glaciation during the globally warm early Late Pliocene.
AB - The early Late Pliocene (3.6 to ~3.0 million years ago) is the last extended
interval in Earth's history when atmospheric CO2 concentrations were comparable
to today's and global climate was warmer. Yet a severe global glaciation during
marine isotope stage (MIS) M2 interrupted this phase of global warmth ~3.30
million years ago, and is seen as a premature attempt of the climate system to
establish an ice-age world. Here we propose a conceptual model for the glaciation
and deglaciation of MIS M2 based on geochemical and palynological records from
five marine sediment cores along a Caribbean to eastern North Atlantic transect.
Our records show that increased Pacific-to-Atlantic flow via the Central American
Seaway weakened the North Atlantic Current and attendant northward heat transport
prior to MIS M2. The consequent cooling of the northern high latitude oceans
permitted expansion of the continental ice sheets during MIS M2, despite near
modern atmospheric CO2 concentrations. Sea level drop during this glaciation
halted the inflow of Pacific water to the Atlantic via the Central American
Seaway, allowing the build-up of a Caribbean Warm Pool. Once this warm pool was
large enough, the Gulf Stream-North Atlantic Current system was reinvigorated,
leading to significant northward heat transport that terminated the glaciation.
Before and after MIS M2, heat transport via the North Atlantic Current was
crucial in maintaining warm climates comparable to those predicted for the end of
this century.
PMID- 24349080
TI - Mechanistic phenotypes: an aggregative phenotyping strategy to identify disease
mechanisms using GWAS data.
AB - A single mutation can alter cellular and global homeostatic mechanisms and give
rise to multiple clinical diseases. We hypothesized that these disease mechanisms
could be identified using low minor allele frequency (MAF<0.1) non-synonymous
SNPs (nsSNPs) associated with "mechanistic phenotypes", comprised of collections
of related diagnoses. We studied two mechanistic phenotypes: (1) thrombosis,
evaluated in a population of 1,655 African Americans; and (2) four groupings of
cancer diagnoses, evaluated in 3,009 white European Americans. We tested
associations between nsSNPs represented on GWAS platforms and mechanistic
phenotypes ascertained from electronic medical records (EMRs), and sought
enrichment in functional ontologies across the top-ranked associations. We used a
two-step analytic approach whereby nsSNPs were first sorted by the strength of
their association with a phenotype. We tested associations using two reverse
genetic models and standard additive and recessive models. In the second step, we
employed a hypothesis-free ontological enrichment analysis using the sorted
nsSNPs to identify functional mechanisms underlying the diagnoses comprising the
mechanistic phenotypes. The thrombosis phenotype was solely associated with
ontologies related to blood coagulation (Fisher's p = 0.0001, FDR p = 0.03),
driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse
genetics models were enriched in DNA repair functions (p = 2*10-5, FDR p = 0.03)
(POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L) while the additive model
showed enrichment related to chromatid segregation (p = 4*10-6, FDR p = 0.005)
(KIF25, PINX1). We were able to replicate nsSNP associations for POLG/FANCI,
BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping
using collections of EMR-derived diagnoses can elucidate fundamental disease
mechanisms.
PMID- 24349082
TI - Cartilage-specific overexpression of ERRgamma results in Chondrodysplasia and
reduced chondrocyte proliferation.
AB - While the role of estrogen receptor-related receptor alpha (ERRalpha) in
chondrogenesis has been investigated, the involvement of ERR gamma (ERRgamma) has
not been determined. To assess the effect of increased ERRgamma activity on
cartilage development in vivo, we generated two transgenic (Tg) lines
overexpressing ERRgamma2 via a chondrocyte-specific promoter; the two lines
exhibited ~3 and ~5 fold increased ERRgamma2 protein expression respectively in
E14.5 Tg versus wild type (WT) limbs. On postnatal day seven (P7), we observed a
4-10% reduction in the size of the craniofacial, axial and appendicular skeletons
in Tg versus WT mice. The reduction in bone length was already present at birth
and did not appear to involve bones that are derived via intramembranous bone
formation as the bones of the calvaria, clavicle, and the mandible developed
normally. Histological analysis of P7 growth plates revealed a reduction in the
length of the Tg versus WT growth plate, the majority of which was attributable
to a reduced proliferative zone. The reduced proliferative zone paralleled a
decrease in the number of Ki67-positive proliferating cells, with no significant
change in apoptosis, and was accompanied by large cell-free swaths of cartilage
matrix, which extended through multiple zones of the growth plate. Using a
bioinformatics approach, we identified known chondrogenesis-associated genes with
at least one predicted ERR binding site in their proximal promoters, as well as
cell cycle regulators known to be regulated by ERRgamma. Of the genes identified,
Col2al, Agg, Pth1r, and Cdkn1b (p27) were significantly upregulated, suggesting
that ERRgamma2 negatively regulates chondrocyte proliferation and positively
regulates matrix synthesis to coordinate growth plate height and organization.
PMID- 24349083
TI - Wild ungulates as disseminators of Shiga toxin-producing Escherichia coli in
urban areas.
AB - BACKGROUND: In 2008, children playing on a soccer field in Colorado were sickened
with a strain of Shiga toxin-producing Escherichia coli (STEC) O157:H7, which was
ultimately linked to feces from wild Rocky Mountain elk. We addressed whether
wild cervids were a potential source of STEC infections in humans and whether
STEC was ubiquitous throughout wild cervid populations in Colorado.
METHODOLOGY/PRINCIPAL FINDINGS: We collected 483 fecal samples from Rocky
Mountain elk and mule deer in urban and non-urban areas. Samples testing positive
for STEC were higher in urban (11.0%) than non-urban (1.6%) areas. Elk fecal
samples in urban areas had a much higher probability of containing STEC, which
increased in both urban and non-urban areas as maximum daily temperature
increased. Of the STEC-positive samples, 25% contained stx1 strains, 34.3%
contained stx2, and 13% contained both stx1 and stx2. Additionally, eaeA genes
were detected in 54.1% of the positive samples. Serotypes O103, and O146 were
found in elk and deer feces, which also have the potential to cause human
illness. CONCLUSIONS/SIGNIFICANCE: The high incidence of stx2 strains combined
with eaeA and E-hyl genes that we found in wild cervid feces is associated with
severe human disease, such as hemolytic uremic syndrome. This is of concern
because there is a very close physical interface between elk and humans in urban
areas that we sampled. In addition, we found a strong relationship between
ambient temperature and incidence of STEC in elk feces, suggesting a higher
incidence of STEC in elk feces in public areas on warmer days, which in turn may
increase the likelihood that people will come in contact with infected feces.
These concerns also have implications to other urban areas where high densities
of coexisting wild cervids and humans interact on a regular basis.
PMID- 24349084
TI - Cellular microRNA miR-181b inhibits replication of mink enteritis virus by
repression of non-structural protein 1 translation.
AB - Mink enteritis virus (MEV) is one of the most important viral pathogens in the
mink industry. Recent studies have showed that microRNAs (miRNAs), small
noncoding RNAs of length ranging from 18-23 nucleotides (nt) participate in host
pathogen interaction networks; however, whether or not miRNAs are involved in MEV
infection has not been reported. Our study revealed that miRNA miR-181b inhibited
replication of MEV in the feline kidney (F81) cell line by targeting the MEV non
structural protein 1 (NS1) messenger RNA (mRNA) coding region, resulting in NS1
translational repression, while MEV infection reduced miR-181b expression. This
is the first description of cellular miRNAs modulating MEV infection in F81
cells, providing further insight into the mechanisms of viral infection, and may
be useful in development of naturally-occurring miRNAs antiviral strategies.
PMID- 24349085
TI - Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by
modulating Ca2+ homeostasis via cross-linking RAP1GDS1.
AB - BACKGROUND: Transglutaminase 2 (TG2) is a protein cross-linking enzyme known to
be associated with the in vivo apoptosis program of T cells. However, its role in
the T cell apoptosis program was not investigated yet. RESULTS: Here we report
that timed overexpression of both the wild type (wt) and the cross-linking mutant
of TG2 induced apoptosis in Jurkat T cells, the wt being more effective. Part of
TG2 colocalised with mitochondria. WtTG2-induced apoptosis was characterized by
enhanced mitochondrial Ca(2+) uptake. Ca(2+)-activated wtTG2 cross-linked RAP1,
GTP-GDP dissociation stimulator 1, an unusual guanine exchange factor acting on
various small GTPases, to induce a yet uncharacterized signaling pathway that was
able to promote the Ca(2+) release from the endoplasmic reticulum via both Ins3P
and ryanodine sensitive receptors leading to a consequently enhanced
mitochondrial Ca(2+)uptake. CONCLUSIONS: Our data indicate that TG2 might act as
a Ca(2+) sensor to amplify endoplasmic reticulum-derived Ca(2+) signals to
enhance mitochondria Ca(2+) uptake. Since enhanced mitochondrial Ca(2+) levels
were previously shown to sensitize mitochondria for various apoptotic signals,
our data demonstrate a novel mechanism through which TG2 can contribute to the
induction of apoptosis in certain cell types. Since, as compared to knock out
cells, physiological levels of TG2 affected Ca(2+) signals in mouse embryonic
fibroblasts similar to Jurkat cells, our data might indicate a more general role
of TG2 in the regulation of mitochondrial Ca(2+) homeostasis.
PMID- 24349087
TI - Effect of site level environmental variables, spatial autocorrelation and
sampling intensity on arthropod communities in an ancient temperate lowland
woodland area.
AB - The interaction of arthropods with the environment and the management of their
populations is a focus of the ecological agenda. Spatial autocorrelation and
under-sampling may generate bias and, when they are ignored, it is hard to
determine if results can in any way be trusted. Arthropod communities were
studied during two seasons and using two methods: window and panel traps, in an
area of ancient temperate lowland woodland of Zebracka (Czech Republic). The
composition of arthropod communities was studied focusing on four site level
variables (canopy openness, diameter in the breast height and height of tree, and
water distance) and finally analysed using two approaches: with and without
effects of spatial autocorrelation. I found that the proportion of variance
explained by space cannot be ignored (~20% in both years). Potential bias in
analyses of the response of arthropods to site level variables without including
spatial co-variables is well illustrated by redundancy analyses. Inclusion of
space led to more accurate results, as water distance and tree diameter were
significant, showing approximately the same ratio of explained variance and
direction in both seasons. Results without spatial co-variables were much more
disordered and were difficult to explain. This study showed that neglecting the
effects of spatial autocorrelation could lead to wrong conclusions in site level
studies and, furthermore, that inclusion of space may lead to more accurate and
unambiguous outcomes. Rarefactions showed that lower sampling intensity, when
appropriately designed, can produce sufficient results without exploitation of
the environment.
PMID- 24349086
TI - Effect of alpha linolenic acid supplementation on serum prostate specific antigen
(PSA): results from the alpha omega trial.
AB - BACKGROUND: Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the
diet. Evidence on health effects of ALA is not conclusive, but some observational
studies found an increased risk of prostate cancer with higher intake of ALA. We
examined the effect of ALA supplementation on serum concentrations of prostate
specific antigen (PSA), a biomarker for prostate cancer. METHODS: The Alpha Omega
Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo
controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and
docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a
2*2 factorial design. Blood was collected at the start and the end of the
intervention period. The present analysis included 1622 patients with a history
of a myocardial infarction, aged 60-80 years with an initial PSA concentration <4
ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads
for 40 months. T-tests and logistic regression were used to assess the effects of
ALA supplementation on changes in serum PSA (both continuously and as a
dichotomous outcome, cut-off point: >4 ng/mL). FINDINGS: Mean serum PSA increased
by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a
difference of 0.10 (95% confidence interval: -0.02 to 0.22) ng/mL (P = 0.12). The
odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI:
0.84-1.58). INTERPRETATION: An additional amount of 2 g of ALA per day increased
PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL
and included no effect. Therefore, more studies are needed to establish whether
or not ALA intake has a clinically significant effect on PSA or prostate cancer.
TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Identifier: NCT00127452. URL:
http://www.clinicaltrials.gov/ct2/show/NCT00127452.
PMID- 24349088
TI - Reconstructing coherent networks from electroencephalography and
magnetoencephalography with reduced contamination from volume conduction or
magnetic field spread.
AB - Volume conduction (VC) and magnetic field spread (MFS) induce spurious
correlations between EEG/MEG sensors, such that the estimation of functional
networks from scalp recordings is inaccurate. Imaginary coherency [1] reduces
VC/MFS artefacts between sensors by assuming that instantaneous interactions are
caused predominantly by VC/MFS and do not contribute to the imaginary part of the
cross-spectral densities (CSDs). We propose an adaptation of the dynamic imaging
of coherent sources (DICS) [2] - a method for reconstructing the CSDs between
sources, and subsequently inferring functional connectivity based on coherences
between those sources. Firstly, we reformulate the principle of imaginary
coherency by performing an eigenvector decomposition of the imaginary part of the
CSD to estimate the power that only contributes to the non-zero phase-lagged
(NZPL) interactions. Secondly, we construct an NZPL-optimised spatial filter with
two a priori assumptions: (1) that only NZPL interactions exist at the source
level and (2) the NZPL CSD at the sensor level is a good approximation of the
projected source NZPL CSDs. We compare the performance of the NZPL method to the
standard method by reconstructing a coherent network from simulated EEG/MEG
recordings. We demonstrate that, as long as there are phase differences between
the sources, the NZPL method reliably detects the underlying networks from EEG
and MEG. We show that the method is also robust to very small phase lags, noise
from phase jitter, and is less sensitive to regularisation parameters. The method
is applied to a human dataset to infer parts of a coherent network underpinning
face recognition.
PMID- 24349089
TI - Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses
CFA-induced inflammatory chronic pain.
AB - GPR40 has been reported to be activated by long-chain fatty acids, such as
docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in
the brain are lacking. The present study focused on the relationship between pain
regulation and GPR40, investigating the functional roles of hypothalamic GPR40
during chronic pain caused using a complete Freund's adjuvant (CFA)-induced
inflammatory chronic pain mouse model. GPR40 protein expression in the
hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14,
after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not
with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after
CFA injection, GFAP protein expression was markedly increased in the
hypothalamus. These increases were significantly inhibited by the
intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent
kinase inhibitor, depending on the decreases in both the increment of GPR40
protein expression and the induction of mechanical allodynia and thermal
hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the
hypothalamus tissue was significantly increased in a flavopiridol reversible
manner at day 1, but not at day 7, after CFA injection. The
intracerebroventricular injection of DHA (50 ug) and GW9508 (1.0 ug), a GPR40
selective agonist, significantly reduced mechanical allodynia and thermal
hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were
inhibited by intracerebroventricular pretreatment with GW1100 (10 ug), a GPR40
antagonist. The protein expression of GPR40 was colocalized with that of beta
endorphin and proopiomelanocortin, and a single intracerebroventricular injection
of GW9508 (1.0 ug) significantly increased the number of neurons double-stained
for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our
findings suggest that hypothalamic GPR40 activated by free long chain fatty acids
might have an important role in this pain control system.
PMID- 24349090
TI - Ribbon synapse plasticity in the cochleae of Guinea pigs after noise-induced
silent damage.
AB - Noise exposure at low levels or low doses can damage hair cell afferent ribbon
synapses without causing permanent threshold shifts. In contrast to reports in
the mouse cochleae, initial damage to ribbon synapses in the cochleae of guinea
pigs is largely repairable. In the present study, we further investigated the
repair process in ribbon synapses in guinea pigs after similar noise exposure. In
the control samples, a small portion of afferent synapses lacked synaptic
ribbons, suggesting the co-existence of conventional no-ribbon and ribbon
synapses. The loss and recovery of hair cell ribbons and post-synaptic densities
(PSDs) occurred in parallel, but the recovery was not complete, resulting in a
permanent loss of less than 10% synapses. During the repair process, ribbons were
temporally separated from the PSDs. A plastic interaction between ribbons and
postsynaptic terminals may be involved in the reestablishment of synaptic contact
between ribbons and PSDs, as shown by location changes in both structures.
Synapse repair was associated with a breakdown in temporal processing, as
reflected by poorer responses in the compound action potential (CAP) of auditory
nerves to time-stress signals. Thus, deterioration in temporal processing
originated from the cochlea. This deterioration developed with the recovery in
hearing threshold and ribbon synapse counts, suggesting that the repaired
synapses had deficits in temporal processing.
PMID- 24349091
TI - Influence of post-traumatic stress disorder on neuroinflammation and cell
proliferation in a rat model of traumatic brain injury.
AB - Long-term consequences of traumatic brain injury (TBI) are closely associated
with the development of severe psychiatric disorders, such as post-traumatic
stress disorder (PTSD), yet preclinical studies on pathological changes after
combined TBI with PTSD are lacking. In the present in vivo study, we assessed
chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal
differentiation in specific brain regions of adult Sprague-Dawley male rats
following controlled cortical impact model of moderate TBI with or without
exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses
revealed no significant differences between sham and PTSD alone treatment across
all brain regions examined, whereas significant exacerbation of OX6-positive
activated microglial cells in the striatum, thalamus, and cerebral peduncle, but
not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared
with PTSD alone and sham treatment. Additional immunohistochemical results
revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI
alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination
of neurogenic niches revealed a significant downregulation of Ki67-positive
proliferating cells, but not DCX-positive neuronally migrating cells in the
neurogenic subgranular zone and subventricular zone for both TBI alone and TBI
PTSD compared to PTSD alone and sham treatment. Comparisons of levels of
neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that
PTSD did not exacerbate the neuropathological hallmarks of TBI. These results
indicate a progressive deterioration of the TBI brain, which, under the
conditions of the present approach, was not intensified by PTSD, at least within
our time window and within the examined areas of the brain. Although the PTSD
manipulation employed here did not exacerbate the pathological effects of TBI,
the observed long-term inflammation and suppressed cell proliferation may evolve
into more severe neurodegenerative diseases and psychiatric disorders currently
being recognized in traumatized TBI patients.
PMID- 24349092
TI - Association of ideal cardiovascular metrics and serum high-sensitivity C-reactive
protein in hypertensive population.
AB - Increased levels of the inflammatory biomarker high-sensitivity C-reactive
protein (hs-CRP) are associated with increased risk of cardiovascular disease.
However, ideal cardiovascular health indicates lower risk of cardiovascular
disease. This study aimed to investigate the effect of ideal cardiovascular
health behaviors and health factors on hs-CRP levels among a hypertensive
population. From 2006 to 2007, a cross-sectional study was conducted to survey
41,476 hypertensive subjects among the employees of Kailuan Corporation. Data
from unified questionnaires and blood biochemical examinations were collected.
The effects of ideal cardiovascular health behaviors and health factors on hs-CRP
levels were evaluated through multivariate logistic regression analysis. A
negative correlation was observed between hs-CRP levels and the number of ideal
cardiovascular health metrics. The mean hs-CRP levels of subjects with zero to
one, two, three, and four to six ideal cardiovascular health metrics were 1.11,
0.96, 0.90, and 0.80 mg/L, respectively (P<0.01). Multivariate logistic
regression analysis revealed that after adjustment for sex, age, triglyceride,
low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and
other risk factors, the risks for subjects with two, three, and four to six ideal
health metrics with serum hs-CRP >3 mg/L were lower than those with zero to one
ideal health metrics, with corresponding odd ratios of 0.86 (95%CI: 0.79-0.93,
P<0.01), 0.76 (95%CI: 0.69-0.83, P<0.01), and 0.68 (95%CI: 0.64-0.75, P<0.01),
respectively. This finding suggests that ideal cardiovascular health behaviors
and health factors were related to decreased hs-CRP levels in a hypertensive
population. CLINICAL TRIAL REGISTRATION: UNIQUE IDENTIFIER: ChiCTR-TNC-11001489.
PMID- 24349093
TI - Determining a clinically relevant strategy for bone tissue engineering: an "all
in-one" study in nude mice.
AB - PURPOSE: Autologous bone grafting (BG) remains the standard reconstruction
strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials,
such as biphasic calcium phosphate (BCP), do not yield consistent results when
used alone and must then be combined with cells through bone tissue engineering
(BTE). In this context, total bone marrow (TBM) and bone marrow-derived
mesenchymal stem cells (MSC) are the primary sources of cellular material used
with biomaterials. However, several other BTE strategies exist, including the use
of growth factors, various scaffolds, and MSC isolated from different tissues.
Thus, clinicians might be unsure as to which method offers patients the most
benefit. For this reason, the aim of this study was to compare eight clinically
relevant BTE methods in an "all-in-one" study. METHODS: We used a transgenic rat
strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC
were harvested. Progenitor cells were then mixed with CaP materials and implanted
subcutaneously into nude mice. After eight weeks, bone formation was evaluated by
histology and scanning electron microscopy, and GFP-expressing cells were tracked
with photon fluorescence microscopy. RESULTS/CONCLUSIONS: Bone formation was
observed in only four groups. These included CaP materials mixed with BG or TBM,
in which abundant de novo bone was formed, and BCP mixed with committed cells
grown in two- and three-dimensions, which yielded limited bone formation.
Fluorescence microscopy revealed that only the TBM and BG groups were positive
for GFP expressing-cells, suggesting that these donor cells were still present in
the host and contributed to the formation of bone. Since the TBM-based procedure
does not require bone harvest or cell culture techniques, but provides abundant
de novo bone formation, we recommend consideration of this strategy for clinical
applications.
PMID- 24349094
TI - Downregulation of cellular protective factors of rumen epithelium in goats fed
high energy diet.
AB - Energy-rich diets can challenge metabolic and protective functions of the rumen
epithelial cells, but the underlying factors are unclear. This study sought to
evaluate proteomic changes of the rumen epithelium in goats fed a low, medium, or
high energy diet. Expression of protein changes were compared by two-dimensional
differential gel electrophoresis followed by protein identification with matrix
assisted laser desorption ionisation tandem time-of-flight mass spectrometry. Of
about 2,000 spots commonly detected in all gels, 64 spots were significantly
regulated, which were traced back to 24 unique proteins. Interestingly, the
expression profiles of several chaperone proteins with important cellular
protective functions such as heat shock cognate 71 kDa protein, peroxiredoxin-6,
serpin H1, protein disulfide-isomerase, and selenium-binding protein were
collectively downregulated in response to high dietary energy supply. Similar
regulation patterns were obtained for some other proteins involved in transport
or metabolic functions. In contrast, metabolic enzymes like retinal dehydrogenase
1 and ATP synthase subunit beta, mitochondrial precursor were upregulated in
response to high energy diet. Lower expressions of chaperone proteins in the
rumen epithelial cells in response to high energy supply may suggest that these
cells were less protected against the potentially harmful rumen toxic compounds,
which might have consequences for rumen and systemic health. Our findings also
suggest that energy-rich diets and the resulting acidotic insult may render rumen
epithelial cells more vulnerable to cellular damage by attenuating their cell
defense system, hence facilitating the impairment of rumen barrier function,
typically observed in energy-rich fed ruminants.
PMID- 24349095
TI - Caring across boundaries versus keeping boundaries intact: links between moral
values and interpersonal orientations.
AB - Prior work has established robust diversity in the extent to which different
moral values are endorsed. Some people focus on values related to caring and
fairness, whereas others assign additional moral weight to ingroup loyalty,
respect for authority and established hierarchies, and purity concerns. Five
studies explore associations between endorsement of distinct moral values and a
suite of interpersonal orientations: Machiavellianism, prosocial resource
distribution, Social Dominance Orientation, and reported likelihood of helping
and not helping kin and close friends versus acquaintances and neighbors. We
found that Machiavellianism (Studies 1, 3, 4, 5) (e.g., amorality, controlling
and status-seeking behaviors) and Social Dominance Orientation (Study 4) were
negatively associated with caring values, and positively associated with
valuation of authority. Those higher in caring values were more likely to choose
prosocial resource distributions (Studies 2, 3, 4) and to report reduced
likelihood of failing to help kin/close friends or acquaintances (Study 4).
Finally, greater likelihood of helping acquaintances was positively associated
with all moral values tested except authority values (Study 4). The current work
offers a novel approach to characterizing moral values and reveals a striking
divergence between two kinds of moral values in particular: caring values and
authority values. Caring values were positively linked with prosociality and
negatively associated with Machiavellianism, whereas authority values were
positively associated with Machiavellianism and Social Dominance Orientation.
PMID- 24349096
TI - Swing-out of the beta3 hybrid domain is required for alphaIIbbeta3 priming and
normal cytoskeletal reorganization, but not adhesion to immobilized fibrinogen.
AB - Structural and functional analyses of integrin alphaIIbbeta3 has implicated swing
out motion of the beta3 hybrid domain in alphaIIbbeta3 activation and ligand
binding. Using data from targeted molecular dynamics (TMD) simulations, we
engineered two disulfide-bonded mutant receptors designed to limit swing-out (XS
O). XS-O mutants cannot bind the high Mr ligand fibrinogen in the presence of an
activating mAb or after introducing mutations into the alphaIIb subunit designed
to simulate inside-out signaling. They also have reduced capacity to be "primed"
to bind fibrinogen by pretreatment with eptifibatide. They can, however, bind the
small RGD venom protein kistrin. Despite their inability to bind soluble
fibrinogen, the XS-O mutants can support adhesion to immobilized fibrinogen,
although such adhesion does not initiate outside-in signaling leading to normal
cytoskeletal reorganization. Collectively, our data further define the biologic
role of beta3 hybrid domain swing-out in both soluble and immobilized high Mr
ligand binding, as well as in priming and outside-in signaling. We also infer
that swing-out is likely to be a downstream effect of receptor extension.
PMID- 24349097
TI - Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast
function.
AB - Myocardial fibrosis, a major pathophysiologic substrate of heart failure with
preserved ejection fraction (HFPEF), is modulated by multiple pathways including
the renin-angiotensin system. Direct renin inhibition is a promising anti
fibrotic therapy since it attenuates the pro-fibrotic effects of renin in
addition to that of other effectors of the renin-angiotensin cascade. Here we
show that the oral renin inhibitor aliskiren has direct effects on collagen
metabolism in cardiac fibroblasts and prevented myocardial collagen deposition in
a non-hypertrophic mouse model of myocardial fibrosis. Adult mice were fed
hyperhomocysteinemia-inducing diet to induce myocardial fibrosis and treated
concomitantly with either vehicle or aliskiren for 12 weeks. Blood pressure and
plasma angiotensin II levels were normal in control and hyperhomocysteinemic mice
and reduced to levels lower than observed in the control group in the groups
treated with aliskiren. Homocysteine-induced myocardial matrix gene expression
and fibrosis were also prevented by aliskiren. In vitro studies using adult rat
cardiac fibroblasts also showed that aliskiren attenuated the pro-fibrotic
pattern of matrix gene and protein expression induced by D,L, homocysteine. Both
in vivo and in vitro studies demonstrated that the Akt pathway was activated by
homocysteine, and that treatment with aliskiren attenuated Akt activation. In
conclusion, aliskiren as mono-therapy has potent and direct effects on myocardial
matrix turnover and beneficial effects on diastolic function.
PMID- 24349098
TI - Elevated plasma SPARC levels are associated with insulin resistance,
dyslipidemia, and inflammation in gestational diabetes mellitus.
AB - OBJECTIVE: Recent studies suggested that secreted protein acidic and rich in
cysteine (SPARC), a novel adipokine, is a key player in the pathology of obesity
and type 2 diabetes. We aimed to determine whether concentrations of SPARC were
altered in patients with gestational diabetes mellitus (GDM) compared to normal
glucose tolerance (NGT) controls and to investigate the relationships between
SPARC and metabolic parameters in pregnant women. DESIGN/METHODS: Cross-sectional
study of 120 pregnant women with GDM and 60 controls with NGT, in a university
hospital setting. Plasma levels of SPARC, adiponectin, fibroblast growth factor
21 (FGF21), insulin and proinsulin were determined by ELISA. RESULTS: GDM women
had higher SPARC and lower adiponectin than NGT subjects; no difference was found
in FGF21. SPARC levels were the lowest in subjects in the third tertile of
insulin sensitivity index (ISIOGTT) and correlated positively with pre-pregnant
BMI, insulin and 3 h glucose during 100-g OGTT, HOMA-IR, fasting proinsulin,
hsCRP and white blood cells count, and negatively with ISIOGTT, when adjusting
for gestational age. Triglyceride (TG), Apolipoprotein A1, apolipoprotein B and
lipoprotein (a) correlated with SPARC in partial Pearson correlation.
Correlations between SPARC with adiponectin, systolic blood pressure and TG were
marginally significant in partial Spearman correlation analysis. In multivariate
regression analysis, SPARC was an independent negative indicator of ISIOGTT.
CONCLUSIONS: SPARC levels are correlated significantly with inflammation and may
also be correlated with dyslipidemia and represent an independent determinant of
insulin resistance in late pregnancy, indicating a potential role of SPARC in the
pathophysiology of GDM.
PMID- 24349099
TI - Expression and biological activity of the cystine knot bioinsecticide PA1b (Pea
Albumin 1 Subunit b).
AB - The PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin extract from Legume
seeds with lethal activity on several insect pests, such as mosquitoes, some
aphids and cereal weevils. This 37 amino-acid cysteine-rich peptide has been,
until now, obtained by biochemical purification or chemical synthesis. In this
paper, we present our results for the transient production of the peptide in
Nicotiana benthamiana by agro-infiltration, with a yield of about 35 ug/g of
fresh leaves and maximum production 8 days after infiltration. PA1b is part of
the PA1 gene which, after post-translational modifications, encodes two peptides
(PA1b and PA1a). We show that transforming tobacco with the PA1b cDNA alone does
not result in production of the toxin and, in fact, the entire cDNA is necessary,
raising the question of the role of PA1a. We constructed a PA1-cassette, allowing
for the quick "cut/paste" of different PA1b mutants within a conserved PA1 cDNA.
This cassette enabled us to produce the six isoforms of PA1b which exist in pea
seeds. Biological tests revealed that all the isoforms display similar activity,
with the exception of one which is inactive. The lack of activity in this isoform
led us to conclude that the amphiphilic nature of the peptide is necessary for
activity. The possible applications of this expression system for other cysteine
rich biomolecules are discussed.
PMID- 24349100
TI - Location and dynamics of the immunodominant CD8 T cell response to SIVDeltanef
immunization and SIVmac251 vaginal challenge.
AB - Live-attenuated SIV vaccines (LAVs) have been the most effective to date in
preventing or partially controlling infection by wild-type SIV in non-human
primate models of HIV-1 transmission to women acting by mechanisms of protection
that are not well understood. To gain insights into mechanisms of protection by
LAVs that could aid development of effective vaccines to prevent HIV-1
transmission to women, we used in situ tetramer staining to determine whether
increased densities or changes in the local distribution of SIV-specific CD8 T
cells correlated with the maturation of SIVDeltanef vaccine-induced protection
prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated
the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope
response in genital and lymphoid tissues, and found that tetramer+ cells were
present at all time points examined. In the cervical vaginal tissues, most
tetramer+ cells were distributed diffusely throughout the lamina propria or co
localized with other CD8 T cells within lymphoid aggregates. The distribution and
densities of the tetramer+ cells at the portal of entry did not correlate with
the maturation of protection or change after challenge. Given these findings, we
discuss the possibility that changes in other aspects of the immune system,
including the quality of the resident population of virus-specific effector CD8 T
cells could contribute to maturation of protection, as well as the potential for
vaccine strategies that further increase the size and quality of this effector
population to prevent HIV-1 transmission.
PMID- 24349102
TI - Awareness and learning in participatory noise sensing.
AB - The development of ICT infrastructures has facilitated the emergence of new
paradigms for looking at society and the environment over the last few years.
Participatory environmental sensing, i.e. directly involving citizens in
environmental monitoring, is one example, which is hoped to encourage learning
and enhance awareness of environmental issues. In this paper, an analysis of the
behaviour of individuals involved in noise sensing is presented. Citizens have
been involved in noise measuring activities through the WideNoise smartphone
application. This application has been designed to record both objective (noise
samples) and subjective (opinions, feelings) data. The application has been open
to be used freely by anyone and has been widely employed worldwide. In addition,
several test cases have been organised in European countries. Based on the
information submitted by users, an analysis of emerging awareness and learning is
performed. The data show that changes in the way the environment is perceived
after repeated usage of the application do appear. Specifically, users learn how
to recognise different noise levels they are exposed to. Additionally, the
subjective data collected indicate an increased user involvement in time and a
categorisation effect between pleasant and less pleasant environments.
PMID- 24349101
TI - Insights from zebrafish and mouse models on the activity and safety of ar
turmerone as a potential drug candidate for the treatment of epilepsy.
AB - In a previous study, we uncovered the anticonvulsant properties of turmeric oil
and its sesquiterpenoids (ar-turmerone, alpha-, beta-turmerone and alpha
atlantone) in both zebrafish and mouse models of chemically-induced seizures
using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating
the anticonvulsant activity of ar-turmerone further. A more in-depth
anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v.
PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were
evaluated using the beam walking test to assess mouse motor function and balance.
In addition, determination of the concentration-time profile of ar-turmerone was
carried out for a more extended evaluation of its bioavailability in the mouse
brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure
models in mice and modulated the expression patterns of two seizure-related genes
(c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly,
no effects on motor function and balance were observed in mice after treatment
with ar-turmerone even after administering a dose 500-fold higher than the
effective dose in the 6-Hz model. In addition, quantification of its
concentration in mouse brains revealed rapid absorption after i.p.
administration, capacity to cross the BBB and long-term brain residence. Hence,
our results provide additional information on the anticonvulsant properties of ar
turmerone and support further evaluation towards elucidating its mechanism of
action, bioavailability, toxicity and potential clinical application.
PMID- 24349103
TI - The simplest integrated multicellular organism unveiled.
AB - Volvocine green algae represent the "evolutionary time machine" model lineage for
studying multicellularity, because they encompass the whole range of evolutionary
transition of multicellularity from unicellular Chlamydomonas to >500-celled
Volvox. Multicellular volvocalean species including Gonium pectorale and Volvox
carteri generally have several common morphological features to survive as
integrated multicellular organisms such as "rotational asymmetry of cells" so
that the cells become components of the individual and "cytoplasmic bridges
between protoplasts in developing embryos" to maintain the species-specific form
of the multicellular individual before secretion of new extracellular matrix
(ECM). However, these morphological features have not been studied in the four
celled colonial volvocine species Tetrabaena socialis that is positioned in the
most basal lineage within the colonial or multicellular volvocine greens. Here we
established synchronous cultures of T. socialis and carried out
immunofluorescence microscopic and ultrastructural observations to elucidate
these two morphological attributes. Based on immunofluorescence microscopy, four
cells of the mature T. socialis colony were identical in morphology but had
rotational asymmetry in arrangement of microtubular rootlets and separation of
basal bodies like G. pectorale and V. carteri. Ultrastructural observations
clearly confirmed the presence of cytoplasmic bridges between protoplasts in
developing embryos of T. socialis even after the formation of new flagella in
each daughter protoplast within the parental ECM. Therefore, these two
morphological attributes might have evolved in the common four-celled ancestor of
the colonial volvocine algae and contributed to the further increase in cell
number and complexity of the multicellular individuals of this model lineage. T.
socialis is one of the simplest integrated multicellular organisms in which four
identical cells constitute the individual.
PMID- 24349104
TI - Pathogenicity of a microsporidium isolate from the diamondback moth against
Noctuid moths: characterization and implications for microbiological pest
management.
AB - BACKGROUND: Due to problems with chemical control, there is increasing interest
in the use of microsporidia for control of lepidopteran pests. However, there
have been few studies to evaluate the susceptibility of exotic species to
microsporidia from indigenous Lepidoptera. METHODOLOGY/PRINCIPAL FINDINGS: We
investigated some biological characteristics of the microsporidian parasite
isolated from wild Plutella xylostella (PX) and evaluated its pathogenicity on
the laboratory responses of sympatric invasive and resident noctuid moths. There
were significant differences in spore size and morphology between PX and
Spodoptera litura (SL) isolates. Spores of PX isolate were ovocylindrical, while
those of SL were oval. PX spores were 1.05 times longer than those of SL, which
in turn were 1.49 times wider than those of the PX. The timing of infection peaks
was much shorter in SL and resulted in earlier larval death. There were no
noticeable differences in amplicon size (two DNA fragments were each about 1200
base pairs in length). Phylogenetic analysis revealed that the small subunit
(SSU) rRNA gene sequences of the two isolates shared a clade with
Nosema/Vairimorpha sequences. The absence of octospores in infected spodopteran
tissues suggested that PX and SL spores are closely related to Nosema plutellae
and N. bombycis, respectively. Both SL and S. exigua (SE) exhibited
susceptibility to the PX isolate infection, but showed different infection
patterns. Tissular infection was more diverse in the former and resulted in much
greater spore production and larval mortality. Microsporidium-infected larvae
pupated among both infected and control larvae, but adult emergence occurred only
in the second group. CONCLUSION/SIGNIFICANCE: The PX isolate infection prevented
completion of development of most leafworm and beet armyworm larvae. The ability
of the microsporidian isolate to severely infect and kill larvae of both native
and introduced spodopterans makes it a valuable candidate for biocontrol against
lepidopteran pests.
PMID- 24349105
TI - A noise level prediction method based on electro-mechanical frequency response
function for capacitors.
AB - The capacitors in high-voltage direct-current (HVDC) converter stations radiate a
lot of audible noise which can reach higher than 100 dB. The existing noise level
prediction methods are not satisfying enough. In this paper, a new noise level
prediction method is proposed based on a frequency response function considering
both electrical and mechanical characteristics of capacitors. The electro
mechanical frequency response function (EMFRF) is defined as the frequency domain
quotient of the vibration response and the squared capacitor voltage, and it is
obtained from impulse current experiment. Under given excitations, the vibration
response of the capacitor tank is the product of EMFRF and the square of the
given capacitor voltage in frequency domain, and the radiated audible noise is
calculated by structure acoustic coupling formulas. The noise level under the
same excitations is also measured in laboratory, and the results are compared
with the prediction. The comparison proves that the noise prediction method is
effective.
PMID- 24349106
TI - Recipe for a busy bee: microRNAs in Honey Bee caste determination.
AB - Social caste determination in the honey bee is assumed to be determined by the
dietary status of the young larvae and translated into physiological and
epigenetic changes through nutrient-sensing pathways. We have employed
Illumina/Solexa sequencing to examine the small RNA content in the bee larval
food, and show that worker jelly is enriched in miRNA complexity and abundance
relative to royal jelly. The miRNA levels in worker jelly were 7-215 fold higher
than in royal jelly, and both jellies showed dynamic changes in miRNA content
during the 4(th) to 6(th) day of larval development. Adding specific miRNAs to
royal jelly elicited significant changes in queen larval mRNA expression and
morphological characters of the emerging adult queen bee. We propose that miRNAs
in the nurse bee secretions constitute an additional element in the regulatory
control of caste determination in the honey bee.
PMID- 24349107
TI - Inhibition of DNA glycosylases via small molecule purine analogs.
AB - Following the formation of oxidatively-induced DNA damage, several DNA
glycosylases are required to initiate repair of the base lesions that are formed.
Recently, NEIL1 and other DNA glycosylases, including OGG1 and NTH1 were
identified as potential targets in combination chemotherapeutic strategies. The
potential therapeutic benefit for the inhibition of DNA glycosylases was
validated by demonstrating synthetic lethality with drugs that are commonly used
to limit DNA replication through dNTP pool depletion via inhibition of
thymidylate synthetase and dihydrofolate reductase. Additionally, NEIL1
associated synthetic lethality has been achieved in combination with Fanconi
anemia, group G. As a prelude to the development of strategies to exploit the
potential benefits of DNA glycosylase inhibition, it was necessary to develop a
reliable high-throughput screening protocol for this class of enzymes. Using
NEIL1 as the proof-of-principle glycosylase, a fluorescence-based assay was
developed that utilizes incision of site-specifically modified
oligodeoxynucleotides to detect enzymatic activity. This assay was miniaturized
to a 1536-well format and used to screen small molecule libraries for inhibitors
of the combined glycosylase/AP lyase activities. Among the top hits of these
screens were several purine analogs, whose postulated presence in the active site
of NEIL1 was consistent with the paradigm of NEIL1 recognition and excision of
damaged purines. Although a subset of these small molecules could inhibit other
DNA glycosylases that excise oxidatively-induced DNA adducts, they could not
inhibit a pyrimidine dimer-specific glycosylase.
PMID- 24349108
TI - Selection of osteoprogenitors from the jaw periosteum by a specific animal-free
culture medium.
AB - The goal of our research work is to establish mesenchymal osteoprogenitors
derived from human jaw periosteum for tissue engineering applications in oral and
maxillofacial surgery. For future autologous and/or allogeneic transplantations,
some issues must be addressed. On the one hand, animal-free culture conditions
have yet to be established. On the other hand, attempts should be undertaken to
shorten the in vitro culturing process efficiently. The aim of the present study
is to compare and analyze the phenotype of osteoprogenitors from the jaw
periosteum under normal FCS-containing and animal-free culture conditions.
Therefore, we analyzed the proliferation rates of MesenCult-XF medium (MC-) in
comparison to DMEM-cultured JPCs. Whereas jaw periosteal cells (JPCs) show
relatively slow proliferation rates and a fibroblastoid shape under DMEM culture
conditions, MC-cultured JPCs diminished their cell size significantly and
proliferated rapidly. By live-monitoring measurements of adhesion and
proliferation, we made an interesting observation: whereas the proliferation of
the MSCA-1(+) subpopulation and the unseparated cell fraction were favored by the
animal-free culture medium, the proliferation of the MSCA-1(-) subpopulation
seemed to be repressed under these conditions. The alkaline phosphatase
expression pattern showed similar results under both culture conditions.
Comparison of the mineralization capacity revealed an earlier formation of
calcium-phosphate precipitates under MC culture conditions; however, the
mineralization capacity of the DMEM-cultured cells seemed to be higher. We
conclude that the tested animal-free medium is suitable for the in vitro
expansion and even for the specific selection of osteoprogenitor cells derived
from the jaw periosteum.
PMID- 24349109
TI - Expression and functional relevance of cannabinoid receptor 1 in Hodgkin
lymphoma.
AB - BACKGROUND: Cannabinoid receptor 1 (CB1) is expressed in certain types of
malignancies. An analysis of CB1 expression and function in Hodgkin lymphoma
(HL), one of the most frequent lymphomas, was not performed to date. DESIGN AND
METHODS: We examined the distribution of CB1 protein in primary cases of HL.
Using lymphoma derived cell lines, the role of CB1 signaling on cell survival was
investigated. RESULTS: A predominant expression of CB1 was found in Hodgkin-Reed
Sternberg cells in a vast majority of classical HL cases. The HL cell lines L428,
L540 and KM-H2 showed strong CB1-abundance and displayed a dose-dependent decline
of viability under CB1 inhibition with AM251. Further, application of AM251 led
to decrease of constitutively active NFkappaB/p65, a crucial survival factor of
HRS-cells, and was followed by elevation of apoptotic markers in HL cells.
CONCLUSIONS: The present study identifies CB1 as a feature of HL, which might
serve as a potential selective target in the treatment of Hodgkin lymphoma.
PMID- 24349110
TI - Analyzing kernel matrices for the identification of differentially expressed
genes.
AB - One of the most important applications of microarray data is the class prediction
of biological samples. For this purpose, statistical tests have often been
applied to identify the differentially expressed genes (DEGs), followed by the
employment of the state-of-the-art learning machines including the Support Vector
Machines (SVM) in particular. The SVM is a typical sample-based classifier whose
performance comes down to how discriminant samples are. However, DEGs identified
by statistical tests are not guaranteed to result in a training dataset composed
of discriminant samples. To tackle this problem, a novel gene ranking method
namely the Kernel Matrix Gene Selection (KMGS) is proposed. The rationale of the
method, which roots in the fundamental ideas of the SVM algorithm, is described.
The notion of ''the separability of a sample'' which is estimated by performing
[Formula: see text]-like statistics on each column of the kernel matrix, is first
introduced. The separability of a classification problem is then measured, from
which the significance of a specific gene is deduced. Also described is a method
of Kernel Matrix Sequential Forward Selection (KMSFS) which shares the KMGS
method's essential ideas but proceeds in a greedy manner. On three public
microarray datasets, our proposed algorithms achieved noticeably competitive
performance in terms of the B.632+ error rate.
PMID- 24349111
TI - Metarhizium anisopliae pathogenesis of mosquito larvae: a verdict of accidental
death.
AB - Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the
aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The
fungus kills without adhering to the host cuticle. Ingested conidia also fail to
germinate and are expelled in fecal pellets. This study investigates the
mechanism by which this fungus adapted to terrestrial hosts kills aquatic
mosquito larvae. Genes associated with the M. anisopliae early pathogenic
response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated
in the presence of larvae, but the established infection process observed in
terrestrial hosts does not progress and insecticidal destruxins were not
detected. Protease inhibitors reduce larval mortality indicating the importance
of proteases in the host interaction. The Ae. aegypti immune response to M.
anisopliae appears limited, whilst the oxidative stress response gene encoding
for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated
as larval death occurs, and insect mortality appears to be linked to autolysis
through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by
protease inhibitors. Evidence is presented that a traditional host-pathogen
response does not occur as the species have not evolved to interact. M.
anisopliae retains pre-formed pathogenic determinants which mediate host
mortality, but unlike true aquatic fungal pathogens, does not recognise and
colonise the larval host.
PMID- 24349112
TI - Appraisal of space words and allocation of emotion words in bodily space.
AB - The body-specificity hypothesis (BSH) predicts that right-handers and left
handers allocate positive and negative concepts differently on the horizontal
plane, i.e., while left-handers allocate negative concepts on the right-hand side
of their bodily space, right-handers allocate such concepts to the left-hand
side. Similar research shows that people, in general, tend to allocate positive
and negative concepts in upper and lower areas, respectively, in relation to the
vertical plane. Further research shows a higher salience of the vertical plane
over the horizontal plane in the performance of sensorimotor tasks. The aim of
the paper is to examine whether there should be a dominance of the vertical plane
over the horizontal plane, not only at a sensorimotor level but also at a
conceptual level. In Experiment 1, various participants from diverse linguistic
backgrounds were asked to rate the words "up", "down", "left", and "right". In
Experiment 2, right-handed participants from two linguistic backgrounds were
asked to allocate emotion words into a square grid divided into four boxes of
equal areas. Results suggest that the vertical plane is more salient than the
horizontal plane regarding the allocation of emotion words and positively
valenced words were placed in upper locations whereas negatively-valenced words
were placed in lower locations. Together, the results lend support to the BSH
while also suggesting a higher saliency of the vertical plane over the horizontal
plane in the allocation of valenced words.
PMID- 24349114
TI - Extended daily dialysis in acute kidney injury patients: metabolic and fluid
control and risk factors for death.
AB - Intermittent hemodialysis (IHD) and continuous renal replacement therapies (CRRT)
are used as Acute Kidney Injury (AKI) therapy and have certain advantages and
disadvantages. Extended daily dialysis (EDD) has emerged as an alternative to
CRRT in the management of hemodynamically unstable AKI patients, mainly in
developed countries. OBJECTIVES: We hypothesized that EDD is a safe option for
AKI treatment and aimed to describe metabolic and fluid control of AKI patients
undergoing EDD and identify complications and risk factors associated with death.
STUDY SELECTION: This is an observational and retrospective study describing
introduction of EDD at our institution. A total of 231 hemodynamically unstable
AKI patients (noradrenalin dose between 0.3 and 1.0 ucg/kg/min) were assigned to
1367 EDD session. EDD consisted of 6-8 h of HD 6 days a week, with blood flow of
200 ml/min, dialysate flows of 300 ml/min. DATA SYNTHESIS: Mean age was 60.6+/
15.8 years, 97.4% of patients were in the intensive care unit, and sepsis was the
main etiology of AKI (76.2). BUN and creatinine levels stabilized after four
sessions at around 38 and 2.4 mg/dl, respectively. Fluid balance decreased
progressively and stabilized around zero after five sessions. Weekly delivered
Kt/V was 5.94+/-0.7. Hypotension and filter clotting occurred in 47.5 and 12.4%
of treatment session, respectively. Regarding AKI outcome, 22.5% of patients
presented renal function recovery, 5.6% of patients remained on dialysis after 30
days, and 71.9% of patients died. Age and focus abdominal sepsis were identified
as risk factors for death. Urine output and negative fluid balance were
identified as protective factors. CONCLUSIONS: EDD is effective for AKI patients,
allowing adequate metabolic and fluid control. Age, focus abdominal sepsis, and
lower urine output as well as positive fluid balance after two EDD sessions were
associated significantly with death.
PMID- 24349115
TI - Emergence of Streptococcus pyogenes emm102 causing toxic shock syndrome in
Southern Taiwan during 2005-2012.
AB - BACKGROUND: Streptococcal toxic shock syndrome (STSS) is an uncommon but life
threatening disease caused by Streptococcus pyogenes. METHODS: To understand the
clinical and molecular characteristics of STSS, we analyzed clinical data and
explored the emm types, superantigen genes, and pulsed-field gel electrophoresis
of causative S. pyogenes isolates obtained between 2005 and 2012. RESULTS: In
total, 53 patients with STSS were included in this study. The median age of the
patients was 57 years (range: 9-83 years), and 81.1% were male. The most
prevalent underlying disease was diabetes mellitus (45.3%). Skin and soft-tissue
infection accounted for 86.8% of STSS. The overall mortality rate was 32.1%.
Underlying diseases had no statistical impact on mortality. A total of 19
different emm types were identified. The most prevalent emm type was emm102
(18.9%), followed by emm11 (17%), emm1 (11.3%), emm87 (9.4%), and emm89 (7.5%).
There was no statistically significant association between emm type and a fatal
outcome. Among the superantigen genes, speB was the most frequently detected one
(92.5%), followed by smeZ (90.6%), speG (81.1%), speC (39.6%), and speF (39.6%).
The majority of emm102 strains were found to have speB, speC, speG, and smeZ. The
presence of speG was negatively associated with a fatal outcome (P = 0.045).
CONCLUSIONS: Our surveillance revealed the emergence of uncommon emm types,
particularly emm102, causing STSS in southern Taiwan. Characterization of
clinical, epidemiological, and molecular characteristics of STSS will improve our
understanding of this life-threatening disease.
PMID- 24349113
TI - A quantitative comparison of human HT-1080 fibrosarcoma cells and primary human
dermal fibroblasts identifies a 3D migration mechanism with properties unique to
the transformed phenotype.
AB - Here, we describe an engineering approach to quantitatively compare migration,
morphologies, and adhesion for tumorigenic human fibrosarcoma cells (HT-1080s)
and primary human dermal fibroblasts (hDFs) with the aim of identifying
distinguishing properties of the transformed phenotype. Relative adhesiveness was
quantified using self-assembled monolayer (SAM) arrays and proteolytic 3
dimensional (3D) migration was investigated using matrix metalloproteinase (MMP)
degradable poly(ethylene glycol) (PEG) hydrogels ("synthetic extracellular
matrix" or "synthetic ECM"). In synthetic ECM, hDFs were characterized by
vinculin-containing features on the tips of protrusions, multipolar morphologies,
and organized actomyosin filaments. In contrast, HT-1080s were characterized by
diffuse vinculin expression, pronounced beta1-integrin on the tips of
protrusions, a cortically-organized F-actin cytoskeleton, and quantitatively more
rounded morphologies, decreased adhesiveness, and increased directional motility
compared to hDFs. Further, HT-1080s were characterized by contractility-dependent
motility, pronounced blebbing, and cortical contraction waves or constriction
rings, while quantified 3D motility was similar in matrices with a wide range of
biochemical and biophysical properties (including collagen) despite substantial
morphological changes. While HT-1080s were distinct from hDFs for each of the 2D
and 3D properties investigated, several features were similar to WM239a melanoma
cells, including rounded, proteolytic migration modes, cortical F-actin
organization, and prominent uropod-like structures enriched with beta1-integrin,
F-actin, and melanoma cell adhesion molecule (MCAM/CD146/MUC18). Importantly,
many of the features observed for HT-1080s were analogous to cellular changes
induced by transformation, including cell rounding, a disorganized F-actin
cytoskeleton, altered organization of focal adhesion proteins, and a weakly
adherent phenotype. Based on our results, we propose that HT-1080s migrate in
synthetic ECM with functional properties that are a direct consequence of their
transformed phenotype.
PMID- 24349116
TI - Urinary immunoglobulin G to albumin ratio and N-Acetyl-Beta-D-Glucosaminidase as
early predictors of therapeutic response in ANCA-associated glomerulonephritis.
AB - BACKGROUND: The aim of our study was to evaluate the prognostic value of
glomerular and tubular proteinuria and tubular enzymuria as early indicators of
therapeutic response to induction therapy with i.v. pulse cyclophosphamide (CyC)
and methylprednisolone (MP) in patients with antineutrophil cytoplasmic antibody
(ANCA) associated glomerulonephritis. METHODS AND FINDINGS: An observational
single-center study was conducted in 30 patients with ANCA-associated
glomerulonephritis. Patients were divided into subgroups with good or poor
response to CyC therapy according to clinical and laboratory parameters. The
diagnosis of ANCA-associated glomerulonephritis was based on the Chapel-Hill
disease definitions. Good response to induction therapy was significantly
associated with higher absolute values of urine N-acetyl-beta-D-glucosaminidase
(NAG) to creatinine ratio (above 14.83 microcat/mol) and urine immunoglobulin G
(IgG) to albumin ratio (above 0.09) at the time of diagnosis, while albuminuria
or proteinuria did not have any early predictive value. The remission of renal
disease was anticipated as early as 3 months after introduction of induction
therapy in patients with reduction of urine NAG to creatinine ratio below the
baseline value and in patients with at least 24% rise in eGFR. CONCLUSIONS: Urine
IgG to albumin and urine NAG to creatinine ratio are better early predictors of
treatment response in patients with ANCA-associated glomerulonephritis than
proteinuria or albuminuria.
PMID- 24349117
TI - The Muller-Lyer illusion in ant foraging.
AB - The Muller-Lyer illusion is a classical geometric illusion in which the apparent
(perceived) length of a line depends on whether the line terminates in an arrow
tail or arrowhead. This effect may be caused by economic compensation for the gap
between the physical stimulus and visual fields. Here, we show that the Muller
Lyer illusion can also be produced by the foraging patterns of garden ants
(Lasius niger) and that the pattern obtained can be explained by a simple,
asynchronously updated foraging ant model. Our results suggest that the geometric
illusion may be a byproduct of the foraging process, in which local interactions
underlying efficient exploitation can also give rise to global exploration, and
that visual information processing in human could implement similar modulation
between local efficient processing and widespread computation.
PMID- 24349118
TI - Systems biology analysis of Brucella infected Peyer's patch reveals rapid
invasion with modest transient perturbations of the host transcriptome.
AB - Brucella melitensis causes the most severe and acute symptoms of all Brucella
species in human beings and infects hosts primarily through the oral route. The
epithelium covering domed villi of jejunal-ileal Peyer's patches is an important
site of entry for several pathogens, including Brucella. Here, we use the calf
ligated ileal loop model to study temporal in vivo Brucella-infected host
molecular and morphological responses. Our results document Brucella bacteremia
occurring within 30 min after intraluminal inoculation of the ileum without
histopathologic traces of lesions. Based on a system biology Dynamic Bayesian
Network modeling approach (DBN) of microarray data, a very early transient
perturbation of the host enteric transcriptome was associated with the initial
host response to Brucella contact that is rapidly averted allowing invasion and
dissemination. A detailed analysis revealed active expression of Syndecan 2,
Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella
adhesion. Also, two intestinal barrier-related pathways (Tight Junction and
Trefoil Factors Initiated Mucosal Healing) were significantly repressed in the
early stage of infection, suggesting subversion of mucosal epithelial barrier
function to facilitate Brucella transepithelial migration. Simultaneously, the
strong activation of the innate immune response pathways would suggest that the
host mounts an appropriate protective immune response; however, the expression of
the two key genes that encode innate immunity anti-Brucella cytokines such as TNF
alpha and IL12p40 were not significantly changed throughout the study.
Furthermore, the defective expression of Toll-Like Receptor Signaling pathways
may partially explain the lack of proinflammatory cytokine production and
consequently the absence of morphologically detectable inflammation at the site
of infection. Cumulatively, our results indicate that the in vivo pathogenesis of
the early infectious process of Brucella is primarily accomplished by
compromising the mucosal immune barrier and subverting critical immune response
mechanisms.
PMID- 24349119
TI - Health benefits of reducing sugar-sweetened beverage intake in high risk
populations of California: results from the cardiovascular disease (CVD) policy
model.
AB - BACKGROUND: Consumption of sugar-sweetened beverage (SSB) has risen over the past
two decades, with over 10 million Californians drinking one or more SSB per day.
High SSB intake is associated with risk of type 2 diabetes, obesity,
hypertension, and coronary heart disease (CHD). Reduction of SSB intake and the
potential impact on health outcomes in California and among racial, ethnic, and
low-income sub-groups has not been quantified. METHODS: We projected the impact
of reduced SSB consumption on health outcomes among all Californians and
California subpopulations from 2013 to 2022. We used the CVD Policy Model - CA,
an established computer simulation of diabetes and heart disease adapted to
California. We modeled a reduction in SSB intake by 10-20% as has been projected
to result from proposed penny-per-ounce excise tax on SSB and modeled varying
effects of this reduction on health parameters including body mass index, blood
pressure, and diabetes risk. We projected avoided cases of diabetes and CHD, and
associated health care cost savings in 2012 US dollars. RESULTS: Over the next
decade, a 10-20% SSB consumption reduction is projected to result in a 1.8-3.4%
decline in the new cases of diabetes and an additional drop of 0.5-1% in incident
CHD cases and 0.5-0.9% in total myocardial infarctions. The greatest reductions
are expected in African Americans, Mexican Americans, and those with limited
income regardless of race and ethnicity. This reduction in SSB consumption is
projected to yield $320-620 million in medical cost savings associated with
diabetes cases averted and an additional savings of $14-27 million in diabetes
related CHD costs avoided. CONCLUSIONS: A reduction of SSB consumption could
yield substantial population health benefits and cost savings for California. In
particular, racial, ethnic, and low-income subgroups of California could reap the
greatest health benefits.
PMID- 24349120
TI - Global expression profiling of low temperature induced genes in the chilling
tolerant japonica rice Jumli Marshi.
AB - Low temperature is a key factor that limits growth and productivity of many
important agronomical crops worldwide. Rice (Oryza sativa L.) is negatively
affected already at temperatures below +10 degrees C and is therefore denoted as
chilling sensitive. However, chilling tolerant rice cultivars exist and can be
commercially cultivated at altitudes up to 3,050 meters with temperatures
reaching as low as +4 degrees C. In this work, the global transcriptional
response to cold stress (+4 degrees C) was studied in the Nepalese highland
variety Jumli Marshi (spp. japonica) and 4,636 genes were identified as
significantly differentially expressed within 24 hours of cold stress. Comparison
with previously published microarray data from one chilling tolerant and two
sensitive rice cultivars identified 182 genes differentially expressed (DE) upon
cold stress in all four rice cultivars and 511 genes DE only in the chilling
tolerant rice. Promoter analysis of the 182 genes suggests a complex cross-talk
between ABRE and CBF regulons. Promoter analysis of the 511 genes identified over
represented ABRE motifs but not DRE motifs, suggesting a role for ABA signaling
in cold tolerance. Moreover, 2,101 genes were DE in Jumli Marshi alone. By
chromosomal localization analysis, 473 of these cold responsive genes were
located within 13 different QTLs previously identified as cold associated.
PMID- 24349121
TI - DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth:
the generation R study.
AB - Changes in epigenetic programming of embryonic growth genes during pregnancy seem
to affect fetal growth. Therefore, in a population-based prospective birth cohort
in the Netherlands, we examined associations between fetal and infant growth and
DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case
children born small-for-gestational age (SGA, birth weight <-2SDS) and 471
control children. Fetal growth was assessed with serial ultrasound measurements.
Information on birth outcomes was retrieved from medical records. Infant weight
was assessed at three and six months. Methylation was assessed in DNA extracted
from umbilical cord white blood cells. Analyses were performed using linear mixed
models with DNA methylation as dependent variable. The DNA methylation levels of
IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5-61.6)
and 30.0% (25.6-34.2) and in the SGA group 52.0% (43.9-60.9) and 30.5% (23.9
32.9), respectively. The MTHFR region was found to be hypomethylated with limited
variability in the control and SGA group, 2.5% (1.4-4.0) and 2.4% (1.5-3.8),
respectively. SGA was associated with lower IGF2DMR DNA methylation (beta =
1.07, 95% CI -1.93; -0.21, P-value = 0.015), but not with H19 methylation. A
weight gain in the first three months after birth was associated with lower
IGF2DMR DNA methylation (beta = -0.53, 95% CI -0.91; -0.16, P-value = 0.005).
Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA
methylation (P-value<0.05), but not with H19 methylation. Furthermore, our
results suggest a possibility of mediation of DNA methylation in the association
between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA
methylation is associated with fetal and infant growth.
PMID- 24349122
TI - Neural processes underlying the"same"-"different" judgment of two simultaneously
presented objects--an EEG study.
AB - The present study investigated the neural processes underlying "same" and
"different" judgments for two simultaneously presented objects, that varied on
one or both, of two dimensions: color and shape. Participants judged whether or
not the two objects were "same" or "different" on either the color dimension
(color task) or the shape dimension (shape task). The unattended irrelevant
dimension of the objects was either congruent (same-same; different-different) or
incongruent (same-different). ERP data showed a main effect of color congruency
in the time window 190-260 ms post-stimulus presentation and a main effect of
shape congruency in the time window 220-280 ms post-stimulus presentation in both
color and shape tasks. The interaction between color and shape congruency in the
ERP data occurred in a later time window than the two main effects, indicating
that mismatches in task-relevant and task-irrelevant dimensions were processed
automatically and independently before a response was selected. The fact that the
interference of the task-irrelevant dimension occurred after mismatch detection,
supports a confluence model of processing.
PMID- 24349123
TI - Benign and malignant renal cells are differentially inhibited during prolonged
organ preservation.
AB - The worry of potential residual renal cancer cells in donor kidney after
resection of small renal cancer impedes the extensive use of such controversial
donor source. To explore the impacts of organ preservation process on the
survival of renal cancer cells, we detected cell proliferation and viability of
benign and malignant renal cell lines and clinical renal samples after treated
with simulated organ preservation process. It was found that the viability and
proliferation of malignant renal cells are inhibited much more than that of
benign renal cells during prolonged organ preservation. The inhibition of
proliferation in benign renal cells is fully reversible, while in malignant renal
cancer cells is not fully reversible after a certain time. So potential residual
renal cancer cells could be partly inhibited and eliminated by organ preservation
process.
PMID- 24349125
TI - When whole-genome alignments just won't work: kSNP v2 software for alignment-free
SNP discovery and phylogenetics of hundreds of microbial genomes.
AB - Effective use of rapid and inexpensive whole genome sequencing for microbes
requires fast, memory efficient bioinformatics tools for sequence comparison. The
kSNP v2 software finds single nucleotide polymorphisms (SNPs) in whole genome
data. kSNP v2 has numerous improvements over kSNP v1 including SNP gene
annotation; better scaling for draft genomes available as assembled contigs or
raw, unassembled reads; a tool to identify the optimal value of k; distribution
of packages of executables for Linux and Mac OS X for ease of installation and
user-friendly use; and a detailed User Guide. SNP discovery is based on k-mer
analysis, and requires no multiple sequence alignment or the selection of a
single reference genome. Most target sets with hundreds of genomes complete in
minutes to hours. SNP phylogenies are built by maximum likelihood, parsimony, and
distance, based on all SNPs, only core SNPs, or SNPs present in some intermediate
user-specified fraction of targets. The SNP-based trees that result are
consistent with known taxonomy. kSNP v2 can handle many gigabases of sequence in
a single run, and if one or more annotated genomes are included in the target
set, SNPs are annotated with protein coding and other information (UTRs, etc.)
from Genbank file(s). We demonstrate application of kSNP v2 on sets of viral and
bacterial genomes, and discuss in detail analysis of a set of 68 finished E. coli
and Shigella genomes and a set of the same genomes to which have been added 47
assemblies and four "raw read" genomes of H104:H4 strains from the recent
European E. coli outbreak that resulted in both bloody diarrhea and hemolytic
uremic syndrome (HUS), and caused at least 50 deaths.
PMID- 24349124
TI - Phosphorylation of mitogen- and stress-activated protein kinase-1 in astrocytic
inflammation: a possible role in inhibiting production of inflammatory cytokines.
AB - PURPOSE: It is generally accepted that inflammation has a role in the progression
of many central nervous system (CNS) diseases, although the mechanisms through
which this occurs remain unclear. Among mitogen-activated protein kinase (MAPK)
targets, mitogen- and stress-activated protein kinase (MSK1) has been thought to
be involved in the pathology of inflammatory gene expression. In this study, the
roles of MSK1 activation in neuroinflammation were investigated. METHODS: The
bacterial lipopolysaccharide (LPS)-induced brain injury model was performed on
Sprague-Dawley rats. The dynamic expression changes and the cellular location of
p-MSK1 in the brain cortex were detected by Western blot and immunofluorescence
staining. The synthesis of inflammatory cytokines in astrocytes was detected by
enzyme-linked immunosorbent assay (ELISA). RESULTS: Phosphorylated MSK1 (p-MSK1
Thr-581) was induced significantly after intracerebral injection of LPS into the
lateral ventricles of the rat brain. Specific upregulation of p-MSK1 in
astrocytes was also observed in inflamed cerebral cortex. At 1 day after LPS
stimulation, iNOS, TNFalpha expression, and the astrocyte marker glial fibrillary
acidic protein (GFAP) were increased significantly. Also, in vitro studies
indicated that the upregulation of p-MSK1 (Thr-581) may be involved in the
subsequent astrocyte inflammatory process, following LPS challenge. Using an
enzyme-linked immunosorbent assay (ELISA), it was confirmed that treatment with
LPS in primary astrocytes stimulated the synthesis of inflammatory cytokines,
through MAPKs signaling pathways. In cultured primary astrocytes, both knock-down
of total MSK1 by small interfering RNAs (siRNA) or specific mutation of Thr-581
resulted in higher production of certain cytokines, such as TNFalpha and IL-6.
CONCLUSIONS: Collectively, these results suggest that MSK1 phosphorylation is
associated with the regulation of LPS-induced brain injury and possibly acts as a
negative regulator of inflammation.
PMID- 24349126
TI - MHC class II expression in human basophils: induction and lack of functional
significance.
AB - The antigen-presenting abilities of basophils and their role in initiating a Th2
phenotype is a topic of current controversy. We aimed to determine whether human
basophils can be induced to express MHC Class II and act as antigen presenting
cells for T cell stimulation. Isolated human basophils were exposed to a panel of
cytokines and TLR-ligands and assessed for MHC Class II expression. MHC Class II
was expressed in up to 17% of isolated basophils following incubation with a
combination of IL-3, IFN-gamma and GM-CSF for 72 hours. Costimulatory molecules
(CD80 and CD86) were expressed at very low levels after stimulation. Gene
expression analysis of MHC Class II-positive basophils confirmed up-regulation of
HLA-DR, HLA-DM, CD74 and Cathepsin S. However, MHC Class II expressing basophils
were incapable of inducing antigen-specific T cell activation or proliferation.
This is the first report of significant cytokine-induced MHC Class II up
regulation, at both RNA and protein level, in isolated human basophils. By
testing stimulation with relevant T cell epitope peptide as well as whole
antigen, the failure of MHC Class II expressing basophils to induce T cell
response was shown not to be solely due to inefficient antigen uptake and/or
processing.
PMID- 24349127
TI - Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus
replication.
AB - We reported previously that Artemisinin (ART), a widely used anti-malarial drug,
is an inhibitor of in vitro HCV subgenomic replicon replication. We here
demonstrate that ART exerts its antiviral activity also in hepatoma cells
infected with full length infectious HCV JFH-1. We identified a number of ART
analogues that are up to 10-fold more potent and selective as in vitro inhibitors
of HCV replication than ART. The iron donor Hemin only marginally potentiates the
anti-HCV activity of ART in HCV-infected cultures. Carbon-centered radicals have
been shown to be critical for the anti-malarial activity of ART. We demonstrate
that carbon-centered radicals-trapping (the so-called TEMPO) compounds only
marginally affect the anti-HCV activity of ART. This provides evidence that
carbon-centered radicals are not the main effectors of the anti-HCV activity of
the Artemisinin. ART and analogues may possibly exert their anti-HCV activity by
the induction of reactive oxygen species (ROS). The combined anti-HCV activity of
ART or its analogues with L-N-Acetylcysteine (L-NAC) [a molecule that inhibits
ROS generation] was studied. L-NAC significantly reduced the in vitro anti-HCV
activity of ART and derivatives. Taken together, the in vitro anti-HCV activity
of ART and analogues can, at least in part, be explained by the induction of ROS;
carbon-centered radicals may not be important in the anti-HCV effect of these
molecules.
PMID- 24349128
TI - Differential network analysis applied to preoperative breast cancer chemotherapy
response.
AB - In silico approaches are increasingly considered to improve breast cancer
treatment. One of these treatments, neoadjuvant TFAC chemotherapy, is used in
cases where application of preoperative systemic therapy is indicated. Estimating
response to treatment allows or improves clinical decision-making and this, in
turn, may be based on a good understanding of the underlying molecular
mechanisms. Ever increasing amounts of high throughput data become available for
integration into functional networks. In this study, we applied our software tool
ExprEssence to identify specific mechanisms relevant for TFAC therapy response,
from a gene/protein interaction network. We contrasted the resulting active
subnetwork to the subnetworks of two other such methods, OptDis and
KeyPathwayMiner. We could show that the ExprEssence subnetwork is more related to
the mechanistic functional principles of TFAC therapy than the subnetworks of the
other two methods despite the simplicity of ExprEssence. We were able to validate
our method by recovering known mechanisms and as an application example of our
method, we identified a mechanism that may further explain the synergism between
paclitaxel and doxorubicin in TFAC treatment: Paclitaxel may attenuate MELK gene
expression, resulting in lower levels of its target MYBL2, already associated
with doxorubicin synergism in hepatocellular carcinoma cell lines. We tested our
hypothesis in three breast cancer cell lines, confirming it in part. In
particular, the predicted effect on MYBL2 could be validated, and a synergistic
effect of paclitaxel and doxorubicin could be demonstrated in the breast cancer
cell lines SKBR3 and MCF-7.
PMID- 24349129
TI - Molecular evidence for a thymus-independent partial T cell development in a FOXN1
/- athymic human fetus.
AB - The thymus is the primary organ able to support T cell ontogeny, abrogated in
FOXN1(-/-) human athymia. Although evidence indicates that in animal models T
lymphocytes may differentiate at extrathymic sites, whether this process is
really thymus-independent has still to be clarified. In an athymic FOXN1(-/-)
fetus, in which we previously described a total blockage of CD4(+) and partial
blockage of CD8(+) cell development, we investigated whether intestine could play
a role as extrathymic site of T-lymphopoiesis in humans. We document the presence
of few extrathymically developed T lymphocytes and the presence in the intestine
of CD3(+) and CD8(+), but not of CD4(+) cells, a few of them exhibiting a
CD45RA(+) naive phenotype. The expression of CD3epsilonepsilonpTalpha, RAG1 and
RAG2 transcripts in the intestine and TCR gene rearrangement was also documented,
thus indicating that in humans the partial T cell ontogeny occurring at
extrathymic sites is a thymus- and FOXN1-independent process.
PMID- 24349130
TI - Year of birth effects in the historical decline of tuberculosis mortality: a
reconsideration.
AB - Birth cohort patterns in mortality are often used to infer long-lasting impacts
of early life conditions. One of the most widely accepted examples of a birth
cohort effect is that of tuberculosis mortality before the late 1940s. However
the evidential basis for claims of cohort-specific declines in tuberculosis
mortality is very slight. Reanalysis of original or enhanced versions of datasets
used previously to support claims of cohort effects in tuberculosis mortality
indicated that: 1. where the initial decline in tuberculosis mortality occurred
within the period of observation, onset of decline occurred simultaneously in
many age groups, in a pattern indicative of 'period' not cohort-dependent
effects. 2. there was little evidence of 'proportional hazard'-type cohort
patterns in tuberculosis mortality for any female population studied. Therefore
any mechanisms proposed to underlie this type of cohort pattern in male mortality
must be sex-specific. 3. sex ratios of tuberculosis mortality at older ages
peaked in cohorts born around 1900, and resembled cohort sex ratios of lung
cancer mortality. This analysis indicates that age-specific patterns in the
decline in tuberculosis mortality before 1950 are unlikely to reflect
improvements in early life conditions. The patterns observed are generally more
consistent with the influence of factors that reduced mortality simultaneously in
most age groups. Additional influences, possibly smoking habits, impeded the
decline of tuberculosis in older adult males, and produced the sex-specific
shifts in age distributions of mortality that were previously interpreted as
evidence of cohort-dependent mortality decline.
PMID- 24349131
TI - Next generation sequencing analysis of human platelet PolyA+ mRNAs and rRNA
depleted total RNA.
AB - BACKGROUND: Platelets are small anucleate cells circulating in the blood vessels
where they play a key role in hemostasis and thrombosis. Here, we compared
platelet RNA-Seq results obtained from polyA+ mRNA and rRNA-depleted total RNA.
MATERIALS AND METHODS: We used purified, CD45 depleted, human blood platelets
collected by apheresis from three male and one female healthy blood donors. The
Illumina HiSeq 2000 platform was employed to sequence cDNA converted either from
oligo(dT) isolated polyA+ RNA or from rRNA-depleted total RNA. The reads were
aligned to the GRCh37 reference assembly with the TopHat/Cufflinks alignment
package using Ensembl annotations. A de novo assembly of the platelet
transcriptome using the Trinity software package and RSEM was also performed. The
bioinformatic tools HTSeq and DESeq from Bioconductor were employed for further
statistical analyses of read counts. RESULTS: Consistent with previous findings
our data suggests that mitochondrially expressed genes comprise a substantial
fraction of the platelet transcriptome. We also identified high transcript levels
for protein coding genes related to the cytoskeleton function, chemokine
signaling, cell adhesion, aggregation, as well as receptor interaction between
cells. Certain transcripts were particularly abundant in platelets compared with
other cell and tissue types represented by RNA-Seq data from the Illumina Human
Body Map 2.0 project. Irrespective of the different library preparation and
sequencing protocols, there was good agreement between samples from the 4
individuals. Eighteen differentially expressed genes were identified in the two
sexes at 10% false discovery rate using DESeq. CONCLUSION: The present data
suggests that platelets may have a unique transcriptome profile characterized by
a relative over-expression of mitochondrially encoded genes and also of genomic
transcripts related to the cytoskeleton function, chemokine signaling and surface
components compared with other cell and tissue types. The in vivo functional
significance of the non-mitochondrial transcripts remains to be shown.
PMID- 24349132
TI - A RabGAP regulates life-cycle duration via trimeric G-protein cascades in
Dictyostelium discoideum.
AB - BACKGROUND: The life-cycle of cellular slime molds comprises chronobiologically
regulated processes. During the growth phase, the amoeboid cells proliferate at a
definite rate. Upon starvation, they synthesize cAMP as both first and second
messengers in signalling pathways and form aggregates, migrating slugs, and
fruiting bodies, consisting of spores and stalk cells, within 24 h. In
Dictyostelium discoideum, because most growth-specific events cease during
development, proliferative and heterochronic mutations are not considered to be
interrelated and no genetic factor governing the entire life-cycle duration has
ever been identified. METHODOLOGY/PRINCIPAL FINDINGS: Using yeast 2-hybrid
library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a
candidate molecule by which the Dictyostelium Galpha2 subunit directs its
effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of
Rab small GTPases, which orchestrate the intracellular membrane trafficking
involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an
increased growth rate and a shortened developmental period, while an
overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg
3 interacts with 2 Galpha subunits in an activity-dependent manner in vitro.
Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented
the Dd rbg-3-deletion phenotype in D. discoideum, indicating that similar
pathways may be generally conserved in multicellular organisms.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Dd Rbg-3 acts as a key
element regulating the duration of D. discoideum life-span potentially via
trimeric G-protein cascades.
PMID- 24349133
TI - A novel source of cultured podocytes.
AB - Amniotic fluid is in continuity with multiple developing organ systems, including
the kidney. Committed, but still stem-like cells from these organs may thus
appear in amniotic fluid. We report having established for the first time a stem
like cell population derived from human amniotic fluid and possessing
characteristics of podocyte precursors. Using a method of triple positive
selection we obtained a population of cells (hAKPC-P) that can be propagated in
vitro for many passages without immortalization or genetic manipulation. Under
specific culture conditions, these cells can be differentiated to mature
podocytes. In this work we compared these cells with conditionally immortalized
podocytes, the current gold standard for in vitro studies. After in vitro
differentiation, both cell lines have similar expression of the major podocyte
proteins, such as nephrin and type IV collagen, that are characteristic of mature
functional podocytes. In addition, differentiated hAKPC-P respond to angiotensin
II and the podocyte toxin, puromycin aminonucleoside, in a way typical of
podocytes. In contrast to immortalized cells, hAKPC-P have a more nearly normal
cell cycle regulation and a pronounced developmental pattern of specific protein
expression, suggesting their suitability for studies of podocyte development for
the first time in vitro. These novel progenitor cells appear to have several
distinct advantages for studies of podocyte cell biology and potentially for
translational therapies.
PMID- 24349134
TI - Renal function can improve at any stage of chronic kidney disease.
AB - INTRODUCTION: Even though renal function decline is considered relentless in
chronic kidney disease (CKD), improvement has been shown in patients with
hypertensive nephropathy. Whether this can occur in any type of nephropathy and
at any stage is unknown as are the features of patients who improve. METHODS: We
identified 406 patients in the NephroTest cohort with glomerular filtration rates
(mGFR) measured by (51)Cr-EDTA clearance at least 3 times during at least 2 years
of follow-up. Individual examination of mGFR trajectories by 4 independent
nephrologists classified patients as improvers, defined as those showing a
sustained mGFR increase, or nonimprovers. Twelve patients with erratic
trajectories were excluded. Baseline data were compared between improvers and
nonimprovers, as was the number of recommended therapeutic targets achieved over
time (specifically, for systolic and diastolic blood pressure, proteinuria, and
use of renin angiotensin system blockers). RESULTS: Measured GFR improved over
time in 62 patients (15.3%). Their median mGFR slope was +1.88[IQR 1.38, 3.55]
ml/min/year; it was -2.23[-3.9, -0.91] for the 332 nonimprovers. Improvers had
various nephropathies, but not diabetic glomerulopathy or polycystic kidney
disease. They did not differ from nonimprovers for age, sex, cardiovascular
history, or CKD stage, but their urinary albumin excretion rate was lower.
Improvers achieved significantly more recommended therapeutic targets (2.74+/
0.87) than nonimprovers (2.44+/-0.80, p<0.01). They also had fewer CKD-related
metabolic complications and a lower prevalence of 25OH-vitamin-D deficiency.
CONCLUSION: GFR improvement is possible in CKD patients at any CKD stage through
stage 4-5. It is noteworthy that this GFR improvement is associated with a
decrease in the number of metabolic complications over time.
PMID- 24349135
TI - Protection enhances community and habitat stability: evidence from a
mediterranean marine protected area.
AB - Rare evidences support that Marine Protected Areas (MPAs) enhance the stability
of marine habitats and assemblages. Based on nine years of observation (2001
2009) inside and outside a well managed MPA, we assessed the potential of
conservation and management actions to modify patterns of spatial and/or temporal
variability of Posidonia oceanica meadows, the lower midlittoral and the shallow
infralittoral rock assemblages. Significant differences in both temporal
variations and spatial patterns were observed between protected and unprotected
locations. A lower temporal variability in the protected vs. unprotected
assemblages was found in the shallow infralittoral, demonstrating that, at least
at local scale, protection can enhance community stability. Macrobenthos with
long-lived and relatively slow-growing invertebrates and structurally complex
algal forms were homogeneously distributed in space and went through little
fluctuations in time. In contrast, a mosaic of disturbed patches featured
unprotected locations, with small-scale shifts from macroalgal stands to barrens,
and harsh temporal variations between the two states. Opposite patterns of
spatial and temporal variability were found for the midlittoral assemblages.
Despite an overall clear pattern of seagrass regression through time, protected
meadows showed a significantly higher shoot density than unprotected ones,
suggesting a higher resistance to local human activities. Our results support the
assumption that the exclusion/management of human activities within MPAs enhance
the stability of the structural components of protected marine systems, reverting
or arresting threat-induced trajectories of change.
PMID- 24349136
TI - Estimation of quasi-stiffness of the human hip in the stance phase of walking.
AB - This work presents a framework for selection of subject-specific quasi-stiffness
of hip orthoses and exoskeletons, and other devices that are intended to emulate
the biological performance of this joint during walking. The hip joint exhibits
linear moment-angular excursion behavior in both the extension and flexion stages
of the resilient loading-unloading phase that consists of terminal stance and
initial swing phases. Here, we establish statistical models that can closely
estimate the slope of linear fits to the moment-angle graph of the hip in this
phase, termed as the quasi-stiffness of the hip. Employing an inverse dynamics
analysis, we identify a series of parameters that can capture the nearly linear
hip quasi-stiffnesses in the resilient loading phase. We then employ regression
analysis on experimental moment-angle data of 216 gait trials across 26 human
adults walking over a wide range of gait speeds (0.75-2.63 m/s) to obtain a set
of general-form statistical models that estimate the hip quasi-stiffnesses using
body weight and height, gait speed, and hip excursion. We show that the general
form models can closely estimate the hip quasi-stiffness in the extension (R(2) =
92%) and flexion portions (R(2) = 89%) of the resilient loading phase of the
gait. We further simplify the general-form models and present a set of stature
based models that can estimate the hip quasi-stiffness for the preferred gait
speed using only body weight and height with an average error of 27% for the
extension stage and 37% for the flexion stage.
PMID- 24349137
TI - Hospital physicians' influence on gastrointestinal protection during treatment
with non-steroidal anti-inflammatory drugs and acetylsalicylic acid and the
impact on prescribing in primary care.
AB - BACKGROUND: The aim of this study was to describe the use of gastrointestinal
(GI) protection before, during and after hospitalisation for elderly patients
using NSAID or low-dose ASA. METHODS: This study included all elderly patients
(75+) admitted to hospital in the period of 1(st) April 2010 to 31(st) March 2011
at Odense University Hospital, Denmark, who were regular users of NSAID or low
dose ASA before hospital admission, or had one of these drugs initiated during
hospital stay. By using pharmacy dispensing data and a hospital-based
pharmacoepidemiological database, the treatment strategy for the individual
patients was followed across hospital stay. RESULTS: In total, 3,587 patients
were included. Before hospital admission, 93 of 245 NSAID users (38.0%) and 597
of 1994 user of low-dose ASA (29.9%) had used GI protection. During hospital
stay, use of GI protection increased to 75% and 33.9%, respectively. When
hospital physicians initiated new treatment with NSAID or with low-dose ASA, 305
of 555 (55.0%) and 647 of 961 (67.3%) were initiated without concomitant use of
GI protection. When hospital physicians initiated GI protection, 26.8-51.0% were
continued in primary care after discharge. CONCLUSIONS: During hospital stay, the
use of GI protection increases, but when new treatment with NSAIDs or low-dose
ASA is initiated in hospital, the use of gastrointestinal protection is low. The
low use of GI protection is carried on in primary care after discharge.
PMID- 24349138
TI - Predicting future blood demand from thalassemia major patients in Hong Kong.
AB - BACKGROUND: In Hong Kong, thalassemia major (TM) patients utilized up to 9.5% of
blood supply in 2009. For long-term management of blood supply, we predicted the
future blood demand of TM patients for the next 10 years. METHODS AND RESULTS:
Annual individual transfusion data in 2005-2009 and demographic information of
381 TM patients were obtained from the Hong Kong Red Cross Blood Transfusion
Service database. A generalized estimating equation (GEE) model was fitted to
establish the potential relations of blood demand with age, sex, body weight,
year of transfusion and splenectomy, accounted for within-patient correlation.
The fitted model was used to predict future blood demand for the existing
patients by accounting for expected change in body weight and mortality rate. We
also predicted the number of new cases in the future based on age- and sex
specific TM incidence and official population projections. Future blood demand
was predicted by combining blood demand from the existing and new patients.
Female (RR = 0.94, p = 0.006) and history of splenectomy (RR = 0.85, p<0.001)
were significantly associated with lower blood demand, while age and weight had
an inverted U-shape relation with maximal blood demand at around 24 years of age
and 71.8 kg, respectively. We predicted that the total blood demand would
increase 0.81% annually from 13,459 units in 2009 to 15,183 units in 2024, with
new TM cases accounting for 31.7% of the overall blood demand in 2024.
CONCLUSIONS: Our results showed that future annual blood demand from TM patients
would steadily increase in the next 10 years. Reducing incidence of TM cases in
the future (by improving public education, antenatal care, prenatal diagnosis)
and minimizing blood use among existing TM cases (e.g. with hemopoietic stem cell
transplantation) can help relieve the burden on management of future blood
demand.
PMID- 24349139
TI - Deciphering the complex distribution of human immunodeficiency virus type 1
subtypes among different cohorts in Northern Tanzania.
AB - BACKGROUND: Increased understanding of the genetic diversity of HIV-1 is
challenging but important in the development of an effective vaccine. We aimed to
describe the distribution of HIV-1 subtypes in northern Tanzania among women
enrolled in studies preparing for HIV-1 prevention trials (hospitality facility
worker cohorts), and among men and women in an open cohort demographic
surveillance system (Kisesa cohort). METHODS: The polymerase encompassing partial
reverse transcriptase was sequenced and phylogenetic analysis performed and
subtype determined. Questionnaires documented demographic data. We examined
factors associated with subtype using multinomial logistic regression, adjusted
for study, age, and sex. RESULTS: Among 140 individuals (125 women and 15 men),
subtype A1 predominated (54, 39%), followed by C (46, 33%), D (25, 18%) and
unique recombinant forms (URFs) (15, 11%). There was weak evidence to suggest
different subtype frequencies by study (for example, 18% URFs in the Kisesa
cohort versus 5-9% in the hospitality facility-worker cohorts; adjusted relative
risk ratio (aRR) = 2.35 [95% CI 0.59,9.32]; global p = 0.09). Compared to men,
women were less likely to have subtype D versus A (aRR = 0.12 [95% CI 0.02,0.76];
global p = 0.05). There was a trend to suggest lower relative risk of subtype D
compared to A with older age (aRR = 0.44 [95% CI 0.23,0.85] per 10 years; global
p = 0.05). CONCLUSIONS: We observed multiple subtypes, confirming the complex
genetic diversity of HIV-1 strains circulating in northern Tanzania, and found
some differences between cohorts and by age and sex. This has important
implications for vaccine design and development, providing opportunity to
determine vaccine efficacy in diverse HIV-1 strains.
PMID- 24349141
TI - Modeling trends from North American breeding bird survey data: a spatially
explicit approach.
AB - Population trends, defined as interval-specific proportional changes in
population size, are often used to help identify species of conservation
interest. Efficient modeling of such trends depends on the consideration of the
correlation of population changes with key spatial and environmental covariates.
This can provide insights into causal mechanisms and allow spatially explicit
summaries at scales that are of interest to management agencies. We expand the
hierarchical modeling framework used in the North American Breeding Bird Survey
(BBS) by developing a spatially explicit model of temporal trend using a
conditional autoregressive (CAR) model. By adopting a formal spatial model for
abundance, we produce spatially explicit abundance and trend estimates. Analyses
based on large-scale geographic strata such as Bird Conservation Regions (BCR)
can suffer from basic imbalances in spatial sampling. Our approach addresses this
issue by providing an explicit weighting based on the fundamental sample
allocation unit of the BBS. We applied the spatial model to three species from
the BBS. Species have been chosen based upon their well-known population change
patterns, which allows us to evaluate the quality of our model and the biological
meaning of our estimates. We also compare our results with the ones obtained for
BCRs using a nonspatial hierarchical model (Sauer and Link 2011). Globally,
estimates for mean trends are consistent between the two approaches but spatial
estimates provide much more precise trend estimates in regions on the edges of
species ranges that were poorly estimated in non-spatial analyses. Incorporating
a spatial component in the analysis not only allows us to obtain relevant and
biologically meaningful estimates for population trends, but also enables us to
provide a flexible framework in order to obtain trend estimates for any area.
PMID- 24349140
TI - A metagenomic framework for the study of airborne microbial communities.
AB - Understanding the microbial content of the air has important scientific, health,
and economic implications. While studies have primarily characterized the
taxonomic content of air samples by sequencing the 16S or 18S ribosomal RNA gene,
direct analysis of the genomic content of airborne microorganisms has not been
possible due to the extremely low density of biological material in airborne
environments. We developed sampling and amplification methods to enable adequate
DNA recovery to allow metagenomic profiling of air samples collected from indoor
and outdoor environments. Air samples were collected from a large urban building,
a medical center, a house, and a pier. Analyses of metagenomic data generated
from these samples reveal airborne communities with a high degree of diversity
and different genera abundance profiles. The identities of many of the taxonomic
groups and protein families also allows for the identification of the likely
sources of the sampled airborne bacteria.
PMID- 24349143
TI - Incorrect citations give unfair credit to review authors in ecology journals.
AB - The number of citations that papers receive has become significant in measuring
researchers' scientific productivity, and such measurements are important when
one seeks career opportunities and research funding. Skewed citation practices
can thus have profound effects on academic careers. We investigated (i) how
frequently authors misinterpret original information and (ii) how frequently
authors inappropriately cite reviews instead of the articles upon which the
reviews are based. To reach this aim, we carried a survey of ecology journals
indexed in the Web of Science and assessed the appropriateness of citations of
review papers. Reviews were significantly more often cited than regular articles.
In addition, 22% of citations were inaccurate, and another 15% unfairly gave
credit to the review authors for other scientists' ideas. These practices should
be stopped, mainly through more open discussion among mentors, researchers and
students.
PMID- 24349142
TI - Hypoxic tumor environments exhibit disrupted collagen I fibers and low
macromolecular transport.
AB - Hypoxic tumor microenvironments result in an aggressive phenotype and resistance
to therapy that lead to tumor progression, recurrence, and metastasis. While poor
vascularization and the resultant inadequate drug delivery are known to
contribute to drug resistance, the effect of hypoxia on molecular transport
through the interstitium, and the role of the extracellular matrix (ECM) in
mediating this transport are unexplored. The dense mesh of fibers present in the
ECM can especially influence the movement of macromolecules. Collagen 1 (Col1)
fibers form a key component of the ECM in breast cancers. Here we characterized
the influence of hypoxia on macromolecular transport in tumors, and the role of
Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer
xenograft model engineered to express red fluorescent protein under hypoxia.
Magnetic resonance imaging of macromolecular transport was combined with second
harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed
significantly decreased Col1 fiber density and volume, as well as significantly
lower macromolecular draining and pooling rates, than normoxic regions. Regions
adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and
increased macromolecular transport. These data suggest that Col1 fibers may
facilitate macromolecular transport in tumors, and their reduction in hypoxic
regions may reduce this transport. Decreased macromolecular transport in hypoxic
regions may also contribute to poor drug delivery and tumor recurrence in hypoxic
regions. High Col1 fiber density observed around hypoxic regions may facilitate
the escape of aggressive cancer cells from hypoxic regions.
PMID- 24349144
TI - Insertion of a specific fungal 3'-phosphoadenosine-5'-phosphatase motif into a
plant homologue improves halotolerance and drought tolerance of plants.
AB - Soil salinity and drought are among the most serious agricultural and
environmental problems of today. Therefore, investigations of plant resistance to
abiotic stress have received a lot of attention in recent years. In this study,
we identified the complete coding sequence of a 3'-phosphoadenosine-5'
phosphatase protein, ApHal2, from the halotolerant yeast Aureobasidium pullulans.
Expression of the ApHAL2 gene in a Saccharomyces cerevisiae hal2 mutant
complemented the mutant auxotrophy for methionine, and rescued the growth of the
hal2 mutant in media with high NaCl concentrations. A 21-amino-acids-long region
of the ApHal2 enzyme was inserted into the Arabidopsis thaliana homologue of
Hal2, the SAL1 phosphatase. The inserted sequence included the META motif, which
has previously been implicated in increased sodium tolerance of the Hal2
homologue from a related fungal species. Transgenic Arabidopsis plants
overexpressing this modified SAL1 (mSAL1) showed improved halotolerance and
drought tolerance. In a medium with an elevated salt concentration, mSAL1
expressing plants were twice as likely to have roots in a higher length category
in comparison with the wild-type Arabidopsis and with plants overexpressing the
native SAL1, and had 5% to 10% larger leaf surface area under moderate and severe
salt stress, respectively. Similarly, after moderate drought exposure, the mSAL1
expressing plants showed 14% increased dry weight after revitalisation, with no
increase in dry weight of the wild-type plants. With severe drought, plants
overexpressing native SAL1 had the worst rehydration success, consistent with the
recently proposed role of SAL1 in severe drought. This was not observed for
plants expressing mSAL1. Therefore, the presence of this fungal META motif
sequence is beneficial under conditions of increased salinity and moderate
drought, and shows no drawbacks for plant survival under severe drought. This
demonstrates that adaptations of extremotolerant fungi should be considered as a
valuable resource for improving stress-tolerance in plant breeding in the future.
PMID- 24349145
TI - The relationship between economic status, knowledge on dengue, risk perceptions
and practices.
AB - The reemergence of dengue as an important public health problem reflects the
difficulties in sustaining vertically organized, effective, control programs and
the need for community-based strategies for Aedes aegypti control that result in
behavioral change. We aimed to disentangle the relationships between underlying
determinants of dengue related practices. We conducted a cross-sectional study in
780 households in La Lisa, Havana, Cuba. A questionnaire and an observation guide
were administrated to collect information on variables related to economic
status, knowledge on dengue, risk perception and practices associated with Aedes
aegypti breading sites. To test a conceptual model that hypothesized direct
relationships among all these constructs, we first used Exploratory Factor
Analysis with Principal Component Analysis to establish the relationship between
observed variables and the underlying latent variables. Subsequently, we tested
whether the observed data supported the conceptual model through Confirmatory
Factor Analysis. Exploratory Factor Analysis indicated that the items measured
could be reduced into five factors with an eigenvalue >1.0: Knowledge on dengue,
Intradomiciliar risk practices, Peridomiciliar risk practices, Risk perception
and Economic status. The proportion of the total variance in the data explained
by these five factors was 74.3%. The Confirmatory Factor Analysis model differed
from our hypothesized conceptual model. Only Knowledge on dengue had a
significant, direct, positive, effect on Practices. There was also a direct
association of Economic status with Knowledge on dengue, but not with Risk
perception and Practices. Clarifying the relationship between direct and indirect
determinants of dengue related practices contributes to a better understanding of
the potential effect of Information Education and Communication on practices and
on the reduction of Aedes aegypti breeding sites and provides inputs for
designing a community based strategy for dengue control.
PMID- 24349146
TI - Influence of lifestyle factors on mammographic density in postmenopausal women.
AB - BACKGROUND: Mammographic density is a strong risk factor for breast cancer. Apart
from hormone replacement therapy (HRT), little is known about lifestyle factors
that influence breast density. METHODS: We examined the effect of smoking,
alcohol and physical activity on mammographic density in a population-based
sample of postmenopausal women without breast cancer. Lifestyle factors were
assessed by a questionnaire and percentage and area measures of mammographic
density were measured using computer-assisted software. General linear models
were used to assess the association between lifestyle factors and mammographic
density and effect modification by body mass index (BMI) and HRT was studied.
RESULTS: Overall, alcohol intake was positively associated with percent
mammographic density (P trend = 0.07). This association was modified by HRT use
(P interaction = 0.06): increasing alcohol intake was associated with increasing
percent density in current HRT users (P trend = 0.01) but not in non-current
users (P trend = 0.82). A similar interaction between alcohol and HRT was found
for the absolute dense area, with a positive association being present in current
HRT users only (P interaction = 0.04). No differences in mammographic density
were observed across categories of smoking and physical activity, neither overall
nor in stratified analyses by BMI and HRT use. CONCLUSIONS: Increasing alcohol
intake is associated with an increase in mammography density, whereas smoking and
physical activity do not seem to influence density. The observed interaction
between alcohol and HRT may pose an opportunity for HRT users to lower their
mammographic density and breast cancer risk.
PMID- 24349148
TI - Imported dengue cases, weather variation and autochthonous dengue incidence in
Cairns, Australia.
AB - BACKGROUND: Dengue fever (DF) outbreaks often arise from imported DF cases in
Cairns, Australia. Few studies have incorporated imported DF cases in the
estimation of the relationship between weather variability and incidence of
autochthonous DF. The study aimed to examine the impact of weather variability on
autochthonous DF infection after accounting for imported DF cases and then to
explore the possibility of developing an empirical forecast system.
METHODOLOGY/PRINCIPAL FINDS: Data on weather variables, notified DF cases
(including those acquired locally and overseas), and population size in Cairns
were supplied by the Australian Bureau of Meteorology, Queensland Health, and
Australian Bureau of Statistics. A time-series negative-binomial hurdle model was
used to assess the effects of imported DF cases and weather variability on
autochthonous DF incidence. Our results showed that monthly autochthonous DF
incidences were significantly associated with monthly imported DF cases (Relative
Risk (RR):1.52; 95% confidence interval (CI): 1.01-2.28), monthly minimum
temperature ((o)C) (RR: 2.28; 95% CI: 1.77-2.93), monthly relative humidity (%)
(RR: 1.21; 95% CI: 1.06-1.37), monthly rainfall (mm) (RR: 0.50; 95% CI: 0.31
0.81) and monthly standard deviation of daily relative humidity (%) (RR: 1.27;
95% CI: 1.08-1.50). In the zero hurdle component, the occurrence of monthly
autochthonous DF cases was significantly associated with monthly minimum
temperature (Odds Ratio (OR): 1.64; 95% CI: 1.01-2.67). CONCLUSIONS/SIGNIFICANCE:
Our research suggested that incidences of monthly autochthonous DF were strongly
positively associated with monthly imported DF cases, local minimum temperature
and inter-month relative humidity variability in Cairns. Moreover, DF outbreak in
Cairns was driven by imported DF cases only under favourable seasons and weather
conditions in the study.
PMID- 24349147
TI - Healthy lifestyles reduce the incidence of chronic diseases and dementia:
evidence from the Caerphilly cohort study.
AB - BACKGROUND: Healthy lifestyles based on non-smoking, an acceptable BMI, a high
fruit and vegetable intake, regular physical activity, and low/moderate alcohol
intake, are associated with reductions in the incidence of certain chronic
diseases, but to date there is limited evidence on cognitive function and
dementia. METHODS: In 1979 healthy behaviours were recorded on 2,235 men aged 45
59 years in Caerphilly, UK. During the following 30 years incident diabetes,
vascular disease, cancer and death were recorded, and in 2004 cognitive state was
determined. FINDINGS: Men who followed four or five of the behaviours had an odds
ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and
social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of
healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30,
0.84; P for trend <0.0005), and there was a delay in vascular disease events of
up to 12 years. Cancer incidence was not significantly related to lifestyle
although there was a reduction associated with non-smoking (OR: 0.65; 95% CI:
0.54, 0.79). All-cause mortality was reduced in men following four or five
behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005). After further
adjustment for NART, the OR for men following four or five healthy behaviours was
0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36
(95% CI: 0.07, 1.99; P for trend <0.02) for dementia. The adoption of a healthy
lifestyle by men was low and appears not to have changed during the subsequent 30
years, with under 1% of men following all five of the behaviours and 5% reporting
four or more in 1979 and in 2009. INTERPRETATION: A healthy lifestyle is
associated with increased disease-free survival and reduced cognitive impairment
but the uptake remains low.
PMID- 24349149
TI - Remote source document verification in two national clinical trials networks: a
pilot study.
AB - OBJECTIVE: Barriers to executing large-scale randomized controlled trials include
costs, complexity, and regulatory requirements. We hypothesized that source
document verification (SDV) via remote electronic monitoring is feasible.
METHODS: Five hospitals from two NIH sponsored networks provided remote
electronic access to study monitors. We evaluated pre-visit remote SDV compared
to traditional on-site SDV using a randomized convenience sample of all study
subjects due for a monitoring visit. The number of data values verified and the
time to perform remote and on-site SDV was collected. RESULTS: Thirty-two study
subjects were randomized to either remote SDV (N=16) or traditional on-site SDV
(N=16). Technical capabilities, remote access policies and regulatory
requirements varied widely across sites. In the adult network, only 14 of 2965
data values (0.47%) could not be located remotely. In the traditional on-site SDV
arm, 3 of 2608 data values (0.12%) required coordinator help. In the pediatric
network, all 198 data values in the remote SDV arm and all 183 data values in the
on-site SDV arm were located. Although not statistically significant there was a
consistent trend for more time consumed per data value (minutes +/- SD): Adult
0.50 +/- 0.17 min vs. 0.39 +/- 0.10 min (two-tailed t-test p=0.11); Pediatric
0.99 +/- 1.07 min vs. 0.56 +/- 0.61 min (p=0.37) and time per case report form:
Adult: 4.60 +/- 1.42 min vs. 3.60 +/- 0.96 min (p=0.10); Pediatric: 11.64 +/-
7.54 min vs. 6.07 +/- 3.18 min (p=0.10) using remote SDV. CONCLUSIONS: Because
each site had different policies, requirements, and technologies, a common
approach to assimilating monitors into the access management system could not be
implemented. Despite substantial technology differences, more than 99% of data
values were successfully monitored remotely. This pilot study demonstrates the
feasibility of remote monitoring and the need to develop consistent access
policies for remote study monitoring.
PMID- 24349150
TI - Source-sink estimates of genetic introgression show influence of hatchery strays
on wild chum salmon populations in Prince William Sound, Alaska.
AB - The extent to which stray, hatchery-reared salmon affect wild populations is much
debated. Although experiments show that artificial breeding and culture influence
the genetics of hatchery salmon, little is known about the interaction between
hatchery and wild salmon in a natural setting. Here, we estimated historical and
contemporary genetic population structures of chum salmon (Oncorhynchus keta) in
Prince William Sound (PWS), Alaska, with 135 single nucleotide polymorphism (SNP)
markers. Historical population structure was inferred from the analysis of DNA
from fish scales, which had been archived since the late 1960's for several
populations in PWS. Parallel analyses with microsatellites and a test based on
Hardy-Weinberg proportions showed that about 50% of the fish-scale DNA was cross
contaminated with DNA from other fish. These samples were removed from the
analysis. We used a novel application of the classical source-sink model to
compare SNP allele frequencies in these archived fish-scales (1964-1982) with
frequencies in contemporary samples (2008-2010) and found a temporal shift toward
hatchery allele frequencies in some wild populations. Other populations showed
markedly less introgression, despite moderate amounts of hatchery straying. The
extent of introgression may reflect similarities in spawning time and life
history traits between hatchery and wild fish, or the degree that hybrids return
to a natal spawning area. The source-sink model is a powerful means of detecting
low levels of introgression over several generations.
PMID- 24349152
TI - Reassessing morphological homologies in the early-divergent angiosperm Fenerivia
(annonaceae) based on floral vascular anatomy: significance for interpreting
putative homeotic mutations.
AB - Fenerivia species (Annonaceae) are characterized by a prominent flange
immediately below the perianth, which has been interpreted as synapomorphic for
the genus. The homology of this flange is controversial: previous studies of
Fenerivia heteropetala (an aberrant species, with 12 perianth parts in three
whorls) have suggested that the flange may represent a vestigial calyx resulting
from a disruption to the homeotic control of organ identity during floral
development. Comparative data on floral vasculature in Fenerivia capuronii are
presented to elucidate the homology of the flange in other Fenerivia species
(which possess nine perianth parts in three whorls, typical of most Annonaceae).
The flange in F. capuronii differs from that in F. heteropetala as it is
unvascularized. It is nevertheless suggested that the flange is likely to be
homologous, and that a homeotic mutation in the F. heteropetala lineage resulted
in the formation of a vestigial but vascularized calyx that fused with the
otherwise unvascularized flange.
PMID- 24349151
TI - Tuberculous lymphadenitis in Northern Ethiopia: in a public health and
microbiological perspectives.
AB - BACKGROUND: The actual burden and causative agent of tuberculous lymphadenitis
(TBLN) cases is not well known due to lack of strong surveillance system and
diagnostic facilities in Ethiopia. This study was conducted to determine the
prevalence of TBLN, its causative agent and risk factors for acquiring this
infection. METHODS: A cross-sectional study was conducted from April to May 2012
at four main hospitals and one diagnostic clinic located in northern Ethiopia.
Fine needle aspirates (FNAs) from TBLN suspects were taken for acid fast bacilli
(AFB) microscopy, culture and molecular typing. RESULTS: Among 437 aspirates,
culture yielded AFB in 226 (51.7%) of cases. Sixty one culture negative cases
(30.5% of 200 cases) were positive by Xpert MTB/RIF test. Moreover, a rifampicin
resistant AFB was detected from culture negative cases. The overall prevalence of
FNAs positive TBLN cases was 65.8 %. The BacT/AlerT 3D system proved to be a more
rapid method with higher recovery rate than Lowenstein-Jensen (L-J) and/or
Gottsacker media (P<0.0001). Molecular typing identified all culture positive
isolates as M.tuberculosis. The main risk factors for TBLN were pediatric age (OR
2.8, 95% CI, 1.09- 7.05) and cough (OR 2, 95%CI, 1.09-3.7). CONCLUSIONS: The
results of this study revealed a high prevalence of TBLN in the study sites and
that pediatric age and cough are key predictors of the disease. TBLN is an
important public health problem that needs to be addressed in the area. It is
important to note that MDR strains of TB could be involved and aetiological
confirmation and drug sensitivity testing of TBLN isolates should be expanded.
Further studies on the M.tuberculosis lineages, circulating strains and
transmission dynamics, are recommended.
PMID- 24349153
TI - TNFalpha signals via p66(Shc) to induce E-Selectin, promote leukocyte
transmigration and enhance permeability in human endothelial cells.
AB - Endothelial cells participate in inflammatory events leading to atherogenesis by
regulating endothelial cell permeability via the expression of VE-Cadherin and
beta-catenin and leukocyte recruitment via the expression of E-Selectins and
other adhesion molecules. The protein p66(Shc) acts as a sensor/inducer of
oxidative stress and may promote vascular dysfunction. The objective of this
study was to investigate the role of p66(Shc) in tumor necrosis factor TNFalpha
induced E-Selectin expression and function in human umbilical vein endothelial
cells (HUVEC). Exposure of HUVEC to 50 ng/ml TNFalpha resulted in increased
leukocyte transmigration through the endothelial monolayer and E-Selectin
expression, in association with augmented phosphorylation of both p66(Shc) on
Ser(36) and the stress kinase c-Jun NH2-terminal protein kinase (JNK)-1/2, and
higher intracellular reactive oxygen species (ROS) levels. Overexpression of
p66(Shc) in HUVEC resulted in enhanced p66(Shc) phosphorylation on Ser(36),
increased ROS and E-Selectin levels, and amplified endothelial cell permeability
and leukocyte transmigration through the HUVEC monolayer. Conversely,
overexpression of a phosphorylation-defective p66(Shc) protein, in which Ser(36)
was replaced by Ala, did not augment ROS and E-Selectin levels, nor modify cell
permeability or leukocyte transmigration beyond those found in wild-type cells.
Moreover, siRNA-mediated silencing of p66(Shc) resulted in marked reduction of E
Selectin expression and leukocyte transmigration. In conclusion, p66(Shc) acts as
a novel intermediate in the TNFalpha pathway mediating endothelial dysfunction,
and its action requires JNK-dependent phosphorylation of p66(Shc) on Ser(36).
PMID- 24349154
TI - The activation by glucose of liver membrane nitric oxide synthase in the
synthesis and translocation of glucose transporter-4 in the production of insulin
in the mice hepatocytes.
AB - INTRODUCTION: Glucose has been reported to have an essential role in the
synthesis and secretion of insulin in hepatocytes. As the efflux of glucose is
facilitated from the liver cells into the circulation, the mechanism of
transportation of glucose into the hepatocytes for the synthesis of insulin was
investigated. METHODS: Grated liver suspension (GLS) was prepared by grating
intact liver from adult mice by using a grater. Nitric oxide (NO) was measured by
methemoglobin method. Glucose transporter-4 (Glut-4) was measured by immunoblot
technique using Glut-4 antibody. RESULTS: Incubation of GLS with different
amounts of glucose resulted in the uptake of glucose by the suspension with
increased NO synthesis due to the stimulation of a glucose activated nitric oxide
synthase that was present in the liver membrane. The inhibition of glucose
induced NO synthesis resulted in the inhibition of glucose uptake. Glucose at
0.02M that maximally increased NO synthesis in the hepatocytes led to the
translocation and increased synthesis of Glut-4 by 3.3 fold over the control that
was inhibited by the inhibition of NO synthesis. The glucose induced NO synthesis
was also found to result in the synthesis of insulin, in the presence of glucose
due to the expression of both proinsulin genes I and II in the liver cells.
CONCLUSION: It was concluded that glucose itself facilitated its own
transportation in the liver cells both via Glut-4 and by the synthesis of NO
which had an essential role for insulin synthesis in the presence of glucose in
these cells.
PMID- 24349155
TI - Brassinosteroids regulate plant growth through distinct signaling pathways in
Selaginella and Arabidopsis.
AB - Brassinosteroids (BRs) are growth-promoting steroid hormones that regulate
diverse physiological processes in plants. Most BR biosynthetic enzymes belong to
the cytochrome P450 (CYP) family. The gene encoding the ultimate step of BR
biosynthesis in Arabidopsis likely evolved by gene duplication followed by
functional specialization in a dicotyledonous plant-specific manner. To gain
insight into the evolution of BRs, we performed a genomic reconstitution of
Arabidopsis BR biosynthetic genes in an ancestral vascular plant, the lycophyte
Selaginella moellendorffii. Selaginella contains four members of the CYP90 family
that cluster together in the CYP85 clan. Similar to known BR biosynthetic genes,
the Selaginella CYP90s exhibit eight or ten exons and Selaginella produces a
putative BR biosynthetic intermediate. Therefore, we hypothesized that
Selaginella CYP90 genes encode BR biosynthetic enzymes. In contrast to typical
CYPs in Arabidopsis, Selaginella CYP90E2 and CYP90F1 do not possess amino
terminal signal peptides, suggesting that they do not localize to the endoplasmic
reticulum. In addition, one of the three putative CYP reductases (CPRs) that is
required for CYP enzyme function co-localized with CYP90E2 and CYP90F1.
Treatments with a BR biosynthetic inhibitor, propiconazole, and epi-brassinolide
resulted in greatly retarded and increased growth, respectively. This suggests
that BRs promote growth in Selaginella, as they do in Arabidopsis. However, BR
signaling occurs through different pathways than in Arabidopsis. A sequence
homologous to the Arabidopsis BR receptor BRI1 was absent in Selaginella, but
downstream components, including BIN2, BSU1, and BZR1, were present. Thus, the
mechanism that initiates BR signaling in Selaginella seems to differ from that in
Arabidopsis. Our findings suggest that the basic physiological roles of BRs as
growth-promoting hormones are conserved in both lycophytes and Arabidopsis;
however, different BR molecules and BRI1-based membrane receptor complexes
evolved in these plants.
PMID- 24349157
TI - Chemical camouflage--a frog's strategy to co-exist with aggressive ants.
AB - Whereas interspecific associations receive considerable attention in
evolutionary, behavioural and ecological literature, the proximate bases for
these associations are usually unknown. This in particular applies to
associations between vertebrates with invertebrates. The West-African savanna
frog Phrynomantis microps lives in the underground nest of ponerine ants
(Paltothyreus tarsatus). The ants usually react highly aggressively when
disturbed by fiercely stinging, but the frog is not attacked and lives unharmed
among the ants. Herein we examined the proximate mechanisms for this unusual
association. Experiments with termites and mealworms covered with the skin
secretion of the frog revealed that specific chemical compounds seem to prevent
the ants from stinging. By HPLC-fractionation of an aqueous solution of the
frogs' skin secretion, two peptides of 1,029 and 1,143 Da were isolated and found
to inhibit the aggressive behaviour of the ants. By de novo sequencing using
tandem mass spectrometry, the amino acid sequence of both peptides consisting of
a chain of 9 and 11 residues, respectively, was elucidated. Both peptides were
synthesized and tested, and exhibited the same inhibitory properties as the
original frog secretions. These novel peptides most likely act as an appeasement
allomone and may serve as models for taming insect aggression.
PMID- 24349156
TI - Functionally different pads on the same foot allow control of attachment: stick
insects have load-sensitive "heel" pads for friction and shear-sensitive "toe"
pads for adhesion.
AB - Stick insects (Carausius morosus) have two distinct types of attachment pad per
leg, tarsal "heel" pads (euplantulae) and a pre-tarsal "toe" pad (arolium). Here
we show that these two pad types are specialised for fundamentally different
functions. When standing upright, stick insects rested on their proximal
euplantulae, while arolia were the only pads in surface contact when hanging
upside down. Single-pad force measurements showed that the adhesion of
euplantulae was extremely small, but friction forces strongly increased with
normal load and coefficients of friction were [Formula: see text] 1. The pre
tarsal arolium, in contrast, generated adhesion that strongly increased with
pulling forces, allowing adhesion to be activated and deactivated by shear
forces, which can be produced actively, or passively as a result of the insects'
sprawled posture. The shear-sensitivity of the arolium was present even when
corrected for contact area, and was independent of normal preloads covering
nearly an order of magnitude. Attachment of both heel and toe pads is thus
activated partly by the forces that arise passively in the situations in which
they are used by the insects, ensuring safe attachment. Our results suggest that
stick insect euplantulae are specialised "friction pads" that produce traction
when pressed against the substrate, while arolia are "true" adhesive pads that
stick to the substrate when activated by pulling forces.
PMID- 24349158
TI - Mitochondrial DNA diversity of modern, ancient and wild sheep(Ovis gmelinii
anatolica) from Turkey: new insights on the evolutionary history of sheep.
AB - In the present study, to contribute to the understanding of the evolutionary
history of sheep, the mitochondrial (mt) DNA polymorphisms occurring in modern
Turkish native domestic (n = 628), modern wild (Ovis gmelinii anatolica) (n = 30)
and ancient domestic sheep from Oylum Hoyuk in Kilis (n = 33) were examined
comparatively with the accumulated data in the literature. The lengths (75 bp/76
bp) of the second and subsequent repeat units of the mtDNA control region (CR)
sequences differentiated the five haplogroups (HPGs) observed in the domestic
sheep into two genetic clusters as was already implied by other mtDNA markers:
the first cluster being composed of HPGs A, B, D and the second cluster harboring
HPGs C, E. To manifest genetic relatedness between wild Ovis gmelinii and
domestic sheep haplogroups, their partial cytochrome B sequences were examined
together on a median-joining network. The two parallel but wider aforementioned
clusters were observed also on the network of Ovis gmelenii individuals, within
which domestic haplogroups were embedded. The Ovis gmelinii wilds of the present
day appeared to be distributed on two partially overlapping geographic areas
parallel to the genetic clusters that they belong to (the first cluster being in
the western part of the overall distribution). Thus, the analyses suggested that
the domestic sheep may be the products of two maternally distinct ancestral Ovis
gmelinii populations. Furthermore, Ovis gmelinii anatolica individuals exhibited
a haplotype of HPG A (n = 22) and another haplotype (n = 8) from the second
cluster which was not observed among the modern domestic sheep. HPG E, with the
newly observed members (n = 11), showed signs of expansion. Studies of ancient
and modern mtDNA suggest that HPG C frequency increased in the Southeast Anatolia
from 6% to 22% some time after the beginning of the Hellenistic period, 500 years
Before Common Era (BCE).
PMID- 24349159
TI - Protocol for callus induction and somatic embryogenesis in Moso Bamboo.
AB - Moso bamboo [Phyllostachys heterocycla var. pubescens (Mazel ex J. Houz.) Ohwi]
is one of the most important forest crops in China and the rest of Asia. Although
many sympodial bamboo tissue culture protocols have been established, there is no
protocol available for plantlet regeneration as indicated by callus induction for
monopodial bamboos, such as Moso bamboo. In the present report, embryogenic
callus induction, embryoid development, and germination were established for Moso
bamboo from zygotic seed embryos. Callus was initiated from zygotic embryos after
10-20 d culture on MS media supplemented with 4.0 mg/L 2, 4-D and 0.1 mg/L zeatin
(ZT). About 50% of the explants produced calli, and nearly 15% of the calli were
found to be embryogenic in nature. These embryogenic calli can be subcultured for
proliferation in the Murashige and Skoog media (MS) supplemented with 0.5-2.0
mg/L 2, 4-D. These calli were found to have maintained their capacity for
regeneration even after one year of subculture. The viable somatic embryoids
regenerated in medium containing 5.0-7.0 mg/L ZT. Nearly 5% of the calli were
found capable of regenerating into plantlets directly in MS medium containing 5.0
7.0 mg/L ZT. Root growth was more pronounced when the plantlets were transferred
to medium containing 2.0 mg/L NAA. After 30 days of subculture, the plantlets
were transferred to a greenhouse.
PMID- 24349160
TI - A multistage gene normalization system integrating multiple effective methods.
AB - Gene/protein recognition and normalization is an important preliminary step for
many biological text mining tasks. In this paper, we present a multistage gene
normalization system which consists of four major subtasks: pre-processing,
dictionary matching, ambiguity resolution and filtering. For the first subtask,
we apply the gene mention tagger developed in our earlier work, which achieves an
F-score of 88.42% on the BioCreative II GM testing set. In the stage of
dictionary matching, the exact matching and approximate matching between gene
names and the EntrezGene lexicon have been combined. For the ambiguity resolution
subtask, we propose a semantic similarity disambiguation method based on Munkres'
Assignment Algorithm. At the last step, a filter based on Wikipedia has been
built to remove the false positives. Experimental results show that the presented
system can achieve an F-score of 90.1%, outperforming most of the state-of-the
art systems.
PMID- 24349161
TI - Negative emotion regulation in patients with posttraumatic stress disorder.
AB - OBJECTIVE: To explore the neural mechanisms of negative emotion regulation in
patients with post-traumatic stress disorder (PTSD). METHODS: Twenty PTSD
patients and 20 healthy subjects were recruited. Event-related functional
magnetic resonance imaging (fMRI) was used to investigate the modification of
emotional responses to negative stimuli. Participants were required to regulate
their emotional reactions according to the auditory regulation instructions via
headphones, to maintain, enhance or diminish responses to negative stimuli during
fMRI scans. RESULTS: The PTSD group showed poorer modification performance than
the control group when diminishing responses to negative stimuli. On fMRI, the
PTSD group showed decreased activation in the inferior frontal cortex, inferior
parietal lobule, insula and putamen, and increased activation in posterior
cingulate cortex and amygdala during up-regulation of negative emotion. Similar
decreased activation regions were found during down-regulation of negative
emotion, but no increased activation was found. CONCLUSION: Trauma exposure might
impair the ability to down-regulate negative emotion. The present findings will
improve our understanding of the neural mechanisms of emotion regulation
underlying PTSD.
PMID- 24349162
TI - New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction
in acetaminophen-induced acute liver failure.
AB - The acute liver failure (ALF) induced by acetaminophen (APAP) is closely related
to oxidative damage and depletion of hepatic glutathione, consequently changes in
cell energy metabolism and mitochondrial dysfunction have been observed after
APAP overdose. Diphenyl diselenide [(PhSe)2], a simple organoselenium compound
with antioxidant properties, previously demonstrated to confer hepatoprotection.
However, little is known about the protective mechanism on mitochondria. The main
objective of this study was to investigate the effects (PhSe)2 to reduce
mitochondrial dysfunction and, secondly, compare in the liver homogenate the
hepatoprotective effects of the (PhSe)2 to the N-acetylcysteine (NAC) during APAP
induced ALF to validate our model. Mice were injected intraperitoneal with APAP
(600 mg/kg), (PhSe)2 (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)2 or APAP+NAC,
where the (PhSe)2 or NAC treatment were given 1 h following APAP. The liver was
collected 4 h after overdose. The plasma alanine and aspartate aminotransferase
activities increased after APAP administration. APAP caused a remarkable increase
of oxidative stress markers (lipid peroxidation, reactive species and protein
carbonylation) and decrease of the antioxidant defense in the liver homogenate
and mitochondria. APAP caused a marked loss in the mitochondrial membrane
potential, the mitochondrial ATPase activity, and the rate of mitochondrial
oxygen consumption and increased the mitochondrial swelling. All these effects
were significantly prevented by (PhSe)2. The effectiveness of (PhSe)2 was similar
at a lower dose than NAC. In summary, (PhSe)2 provided a significant improvement
to the mitochondrial redox homeostasis and the mitochondrial bioenergetics
dysfunction caused by membrane permeability transition in the hepatotoxicity APAP
induced.
PMID- 24349163
TI - The network architecture of the Saccharomyces cerevisiae genome.
AB - We propose a network-based approach for surmising the spatial organization of
genomes from high-throughput interaction data. Our strategy is based on methods
for inferring architectural features of networks. Specifically, we employ a
community detection algorithm to partition networks of genomic interactions.
These community partitions represent an intuitive interpretation of genomic
organization from interaction data. Furthermore, they are able to recapitulate
known aspects of the spatial organization of the Saccharomyces cerevisiae genome,
such as the rosette conformation of the genome, the clustering of centromeres, as
well as tRNAs, and telomeres. We also demonstrate that simple architectural
features of genomic interaction networks, such as cliques, can give meaningful
insight into the functional role of the spatial organization of the genome. We
show that there is a correlation between inter-chromosomal clique size and
replication timing, as well as cohesin enrichment. Together, our network-based
approach represents an effective and intuitive framework for interpreting high
throughput genomic interaction data. Importantly, there is a great potential for
this strategy, given the rich literature and extensive set of existing tools in
the field of network analysis.
PMID- 24349165
TI - A collusion-resistant fingerprinting system for restricted distribution of
digital documents.
AB - Digital fingerprinting is a technique that consists of inserting the ID of an
authorized user in the digital content that he requests. This technique has been
mainly used to trace back pirate copies of multimedia content such as images,
audio, and video. This study proposes the use of state-of-the-art digital
fingerprinting techniques in the context of restricted distribution of digital
documents. In particular, the system proposed by Kuribayashi for multimedia
content is investigated. Extensive simulations show the robustness of the
proposed system against average collusion attack. Perceptual transparency of the
fingerprinted documents is also studied. Moreover, by using an efficient Fast
Fourier Transform core and standard computer machines it is shown that the
proposed system is suitable for real-world scenarios.
PMID- 24349164
TI - Evaluation of cytotoxic and anti-inflammatory activities of extracts and lectins
from Moringa oleifera seeds.
AB - BACKGROUND: The extract from Moringa oleifera seeds is used worldwide, especially
in rural areas of developing countries, to treat drinking water. M. oleifera
seeds contain the lectins cmol and WSMoL, which are carbohydrate-binding proteins
that are able to reduce water turbidity because of their coagulant activity.
Studies investigating the ability of natural products to damage normal cells are
essential for the safe use of these substances. This study evaluated the
cytotoxic and anti-inflammatory properties of the aqueous seed extract, the
extract used by population to treat water (named diluted seed extract in this
work), and the isolated lectins cmol and WSMoL. METHODOLOGY/PRINCIPAL FINDINGS:
The data showed that the aqueous seed extract and cmol were potentially cytotoxic
to human peripheral blood mononuclear cells, while WSMoL and diluted seed extract
were not cytotoxic. The M. oleifera aqueous seed extract and the lectins cmol and
WSMoL were weakly/moderately cytotoxic to the NCI-H292, HT-29 and HEp-2 cancer
cell lines and were not hemolytic to murine erythrocytes. Evaluation of acute
toxicity in mice revealed that the aqueous seed extract (2.000 mg/kg) did not
cause systemic toxicity. The aqueous seed extract, cmol and WSMoL (6.25 ug/mL)
and diluted seed extract at 50 ug/mL exhibited anti-inflammatory activity on
lipopolyssaccharide-stimulated murine macrophages by regulating the production of
nitric oxide, TNF-alpha and IL-1beta. The aqueous seed extract reduced leukocyte
migration in a mouse model of carrageenan-induced pleurisy; the myeloperoxidase
activity and nitric oxide, TNF-alpha and IL-1beta levels were similarly reduced.
Histological analysis of the lungs showed that the extract reduced the number of
leukocytes. CONCLUSION/SIGNIFICANCE: This study shows that the extract prepared
according to folk use and WSMoL may be non-toxic to mammalian cells; however, the
aqueous seed extract and cmol may be cytotoxic to immune cells which may explain
the immunosuppressive potential of the extract.
PMID- 24349166
TI - Rapid induction of lipid droplets in Chlamydomonas reinhardtii and Chlorella
vulgaris by Brefeldin A.
AB - Algal lipids are the focus of intensive research because they are potential
sources of biodiesel. However, most algae produce neutral lipids only under
stress conditions. Here, we report that treatment with Brefeldin A (BFA), a
chemical inducer of ER stress, rapidly triggers lipid droplet (LD) formation in
two different microalgal species, Chlamydomonas reinhardtii and Chlorella
vulgaris. LD staining using Nile red revealed that BFA-treated algal cells
exhibited many more fluorescent bodies than control cells. Lipid analyses based
on thin layer chromatography and gas chromatography revealed that the additional
lipids formed upon BFA treatment were mainly triacylglycerols (TAGs). The
increase in TAG accumulation was accompanied by a decrease in the betaine lipid
diacylglyceryl N,N,N-trimethylhomoserine (DGTS), a major component of the
extraplastidic membrane lipids in Chlamydomonas, suggesting that at least some of
the TAGs were assembled from the degradation products of membrane lipids.
Interestingly, BFA induced TAG accumulation in the Chlamydomonas cells regardless
of the presence or absence of an acetate or nitrogen source in the medium. This
effect of BFA in Chlamydomonas cells seems to be due to BFA-induced ER stress, as
supported by the induction of three homologs of ER stress marker genes by the
drug. Together, these results suggest that ER stress rapidly triggers TAG
accumulation in two green microalgae, C. reinhardtii and C. vulgaris. A further
investigation of the link between ER stress and TAG synthesis may yield an
efficient means of producing biofuel from algae.
PMID- 24349168
TI - Co-culture of human bronchial fibroblasts and CD4+ T cells increases Th17
cytokine signature.
AB - BACKGROUND: Airway inflammation is an important characteristic of asthma and has
been associated with airway remodelling and bronchial hyperreactivity. The
mucosal microenvironment composed of structural cells and highly specialised
extracellular matrix is able to amplify and promote inflammation. This
microenvironment leads to the development and maintenance of a specific adaptive
response characterized by Th2 and Th17. Bronchial fibroblasts produce multiple
mediators that may play a role in maintaining and amplifying this response in
asthma. OBJECTIVE: To investigate the role of bronchial fibroblasts obtained from
asthmatic subjects and healthy controls in regulating Th17 response by creating a
local micro-environment that promotes this response in the airways. METHODS:
Human bronchial fibroblasts and CD4(+)T cells were isolated from atopic
asthmatics and non-atopic healthy controls. CD4(+)T were co-cultured with
bronchial fibroblasts of asthmatic subjects and healthy controls. RORc gene
expression was detected by qPCR. Phosphorylated STAT-3 and RORgammat were
evaluated by western blots. Th17 phenotype was measured by flow cytometry. IL-22,
IL17, IL-6 TGF-beta and IL1-beta were assessed by qPCR and ELISA. RESULTS: Co
culture of CD4(+)T cells with bronchial fibroblasts significantly stimulated RORc
expression and induced a significant increase in Th17 cells as characterized by
the percentage of IL-17(+)/CCR6(+) staining in asthmatic conditions. IL-17 and IL
22 were increased in both normal and asthmatic conditions with a significantly
higher amount in asthmatics compared to controls. IL-6, IL-1beta, TGF-beta and IL
23 were significantly elevated in fibroblasts from asthmatic subjects upon co
culture with CD4(+)T cells. IL-23 stimulates IL-6 and IL-1beta expression by
bronchial fibroblasts. CONCLUSION: Interaction between bronchial fibroblasts and
T cells seems to promote specifically Th17 cells profile in asthma. These results
suggest that cellular interaction particularly between T cells and fibroblasts
may play a pivotal role in the regulation of the inflammatory response in asthma.
PMID- 24349167
TI - Carnosine's effect on amyloid fibril formation and induced cytotoxicity of
lysozyme.
AB - Carnosine, a common dipeptide in mammals, has previously been shown to dissemble
alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis
effect has not been thoroughly characterized in other proteins. For a more
complete understanding of carnosine's mechanism of action in amyloid fibril
inhibition, we have investigated the effect of the dipeptide on lysozyme fibril
formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our
study demonstrates a positive correlation between the concentration and
inhibitory effect of carnosine against lysozyme fibril formation. Molecular
docking results show carnosine's mechanism of fibrillogenesis inhibition may be
initiated by binding with the aggregation-prone region of the protein. The
dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal
cells by reducing both apoptotic and necrotic cell deaths. Our study provides
solid support for carnosine's amyloid fibril inhibitory property and its effect
against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights
gained herein may pave way to the discovery of other small molecules that may
exert similar effects against amyloid fibril formation and its associated
neurodegenerative diseases.
PMID- 24349169
TI - Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent
hydroxymycolic acid dehydrogenase.
AB - The ability of Mycobacterium tuberculosis to manipulate and evade human immune
system is in part due to its extraordinarily complex cell wall. One of the key
components of this cell wall is a family of lipids called mycolic acids.
Oxygenation of mycolic acids generating methoxy- and ketomycolic acids enhances
the pathogenic attributes of M. tuberculosis. Thus, the respective enzymes are of
interest in the research on mycobacteria. The generation of methoxy- and
ketomycolic acids proceeds through intermediary formation of hydroxymycolic
acids. While the methyl transferase that generates methoxymycolic acids from
hydroxymycolic acids is known, hydroxymycolic acids dehydrogenase that oxidizes
hydroxymycolic acids to ketomycolic acids has been elusive. We found that
hydroxymycolic acid dehydrogenase is encoded by the rv0132c gene and the enzyme
utilizes F420, a deazaflavin coenzyme, as electron carrier, and accordingly we
called it F420-dependent hydroxymycolic acid dehydrogenase. This is the first
report on the involvement of F420 in the synthesis of a mycobacterial cell
envelope. Also, F420-dependent hydroxymycolic acid dehydrogenase was inhibited by
PA-824, and therefore, it is a previously unknown target for this new
tuberculosis drug.
PMID- 24349170
TI - Biomass partitioning and its relationship with the environmental factors at the
alpine steppe in Northern Tibet.
AB - Alpine steppe is considered to be the largest grassland type on the Tibetan
Plateau. This grassland contributes to the global carbon cycle and is sensitive
to climate changes. The allocation of biomass in an ecosystem affects plant
growth and the overall functioning of the ecosystem. However, the mechanism by
which plant biomass is allocated on the alpine steppe remains unclear. In this
study, biomass allocation and its relationship to environmental factors on the
alpine grassland were studied by a meta-analysis of 32 field sites across the
alpine steppe of the northern Tibetan Plateau. We found that there is less above
ground biomass (M A ) and below-ground biomass (M B ) in the alpine steppe than
there is in alpine meadows and temperate grasslands. By contrast, the root-to
shoot ratio (R:S) in the alpine steppe is higher than it is in alpine meadows and
temperate grasslands. Although temperature maintained the biomass in the alpine
steppe, precipitation was found to considerably influence M A , M B , and R:S, as
shown by ordination space partitioning. After standardized major axis (SMA)
analysis, we found that allocation of biomass on the alpine steppe is supported
by the allometric biomass partitioning hypothesis rather than the isometric
allocation hypothesis. Based on these results, we believe that M A and M B will
decrease as a result of the increased aridity expected to occur in the future,
which will reduce the landscape's capacity for carbon storage.
PMID- 24349171
TI - Two randomized trials provide no consistent evidence for nonmusical cognitive
benefits of brief preschool music enrichment.
AB - Young children regularly engage in musical activities, but the effects of early
music education on children's cognitive development are unknown. While some
studies have found associations between musical training in childhood and later
nonmusical cognitive outcomes, few randomized controlled trials (RCTs) have been
employed to assess causal effects of music lessons on child cognition and no
clear pattern of results has emerged. We conducted two RCTs with preschool
children investigating the cognitive effects of a brief series of music classes,
as compared to a similar but non-musical form of arts instruction (visual arts
classes, Experiment 1) or to a no-treatment control (Experiment 2). Consistent
with typical preschool arts enrichment programs, parents attended classes with
their children, participating in a variety of developmentally appropriate arts
activities. After six weeks of class, we assessed children's skills in four
distinct cognitive areas in which older arts-trained students have been reported
to excel: spatial-navigational reasoning, visual form analysis, numerical
discrimination, and receptive vocabulary. We initially found that children from
the music class showed greater spatial-navigational ability than did children
from the visual arts class, while children from the visual arts class showed
greater visual form analysis ability than children from the music class
(Experiment 1). However, a partial replication attempt comparing music training
to a no-treatment control failed to confirm these findings (Experiment 2), and
the combined results of the two experiments were negative: overall, children
provided with music classes performed no better than those with visual arts or no
classes on any assessment. Our findings underscore the need for replication in
RCTs, and suggest caution in interpreting the positive findings from past studies
of cognitive effects of music instruction.
PMID- 24349172
TI - Extramotor damage is associated with cognition in primary lateral sclerosis
patients.
AB - OBJECTIVES: This is a cross-sectional study aimed at investigating cognitive
performances in patients with primary lateral sclerosis (PLS) and using diffusion
tensor (DT) magnetic resonance imaging (MRI) to determine the topographical
distribution of microstructural white matter (WM) damage in patients with or
without cognitive deficits. METHODS: DT MRI scans were obtained from 21 PLS
patients and 35 age- and sex-matched healthy controls. All PLS patients underwent
a comprehensive neuropsychological battery. Tract-based-spatial-statistics (TBSS)
was used to perform a whole-brain voxel-wise analysis of fractional anisotropy
(FA), axial, radial (radD) and mean diffusivity (MD). RESULTS: Ten PLS patients
had abnormal scores in at least one neuropsychological test (PLS with cognitive
deficits, PLS-cd). Compared with healthy controls and cognitively unimpaired PLS
patients (PLS-cu), PLS-cd cases showed decreased FA and increased MD and radD in
the corticospinal tract (CST), corpus callosum, brainstem, anterior limb of
internal capsule, superior and inferior longitudinal fasciculi, fornix, thalamic
radiations, and parietal lobes, bilaterally. Compared with healthy controls, PLS
cd patients showed further decreased FA and increased radD in the cerebellar WM,
bilaterally. Compared with controls, PLS-cu patients showed decreased FA in the
mid-body of corpus callosum. In PLS, executive and language test scores
correlated with WM damage. CONCLUSIONS: This is the first study evaluating the
relationship between cognitive performance and WM tract damage in PLS patients.
PLS can be associated with a multi-domain cognitive impairment. WM damage to
interhemispheric, limbic and major associative WM tracts seem to be the
structural correlate of cognitive abnormalities in these patients.
PMID- 24349173
TI - In silico, in vitro and in vivo analysis of binding affinity between N and C
domains of Clostridium perfringens alpha toxin.
AB - Clostridium perfringens alpha toxin/phospholipase C (CP-PLC) is one of the most
potent bacterial toxins known to cause soft tissue infections like gas gangrene
in humans and animals. It is the first bacterial toxin demonstrated to be an
enzyme with phospholipase, sphingomyelinase and lecithinase activities. The toxin
is comprised of an enzymatic N-domain and a binding C-domain interconnected by a
flexible linker. The N-domain alone is non-toxic to mammalian cells, but
incubation with C-domain restores the toxicity, the mechanism of which is still
not elucidated. The objectives of the current study were to investigate the
formation of a stable N and C-domain complex, to determine possible interactions
between the two domains in silico and to characterize the in vitro and in vivo
correlates of the interaction. To establish the existence of a stable N and C
domain hybrid, in vitro pull down assay and dot-Far Western blotting assays were
employed, where it was clearly revealed that the two domains bound to each other
to form an intermediate. Using bioinformatics tools like MetaPPISP, PatchDock and
FireDock, we predicted that the two domains may interact with each other through
electrostatic interactions between at least six pairs of amino acids. This N and
C-domains interacted with each other in 1:1 ratio and the hybrid lysed mouse
erythrocytes in a slower kinetics when compared with wild type native Cp-PLC.
BALB/c mice when challenged with N and C-domain hybrid demonstrated severe
myonecrosis at the site of injection while no death was observed. Our results
provide further insight into better understanding the mechanism for the toxicity
of Cp-PLC N and C-domain mixture.
PMID- 24349174
TI - Psychosocial functioning and intelligence both partly explain socioeconomic
inequalities in premature death. A population-based male cohort study.
AB - OBJECTIVE: The possible contributions of psychosocial functioning and
intelligence differences to socioeconomic status (SES)-related inequalities in
premature death were investigated. None of the previous studies focusing on
inequalities in mortality has included measures of both psychosocial functioning
and intelligence. METHODS: The study was based on a cohort of 49 321 men born
1949-1951 from the general community in Sweden. Data on psychosocial functioning
and intelligence from military conscription at ~18 years of age were linked with
register data on education, occupational class, and income at 35-39 years of age.
Psychosocial functioning was rated by psychologists as a summary measure of
differences in level of activity, power of initiative, independence, and
emotional stability. Intelligence was measured through a multidimensional test.
Causes of death between 40 and 57 years of age were followed in registers.
RESULTS: The estimated inequalities in all-cause mortality by education and
occupational class were attenuated with 32% (95% confidence interval: 20-45%) and
41% (29-52%) after adjustments for individual psychological differences; both
psychosocial functioning and intelligence contributed to account for the
inequalities. The inequalities in cardiovascular and injury mortality were
attenuated by as much as 51% (24-76%) and 52% (35-68%) after the same
adjustments, and the inequalities in alcohol-related mortality were attenuated by
up to 33% (8-59%). Less of the inequalities were accounted for when those were
measured by level of income, with which intelligence had a weaker correlation.
The small SES-related inequalities in cancer mortality were not attenuated by
adjustment for intelligence. CONCLUSIONS: Differences in psychosocial functioning
and intelligence might both contribute to the explanation of observed SES-related
inequalities in premature death, but the magnitude of their contributions likely
varies with measure of socioeconomic status and cause of death. Both psychosocial
functioning and intelligence should be considered in future studies.
PMID- 24349175
TI - Ginkgo biloba extract individually inhibits JNK activation and induces c-Jun
degradation in human chondrocytes: potential therapeutics for osteoarthritis.
AB - Osteoarthritis (OA) is a common joint disorder with varying degrees of
inflammation. The ideal anti-OA drug should have immunomodulatory effects while
at the same time having limited or no toxicity. We examined the anti-inflammatory
effects of Ginkgo biloba extract (EGb) in interleukin-1 (IL-1)-stimulated human
chondrocytes. Chondrocytes were prepared from cartilage specimens taken from
patients with osteoarthritis who had received total hip or total knee
replacement. The concentrations of chemokines and the degree of cell migration
were determined by ELISA and chemotaxis assays, respectively. The activation of
inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases
(MAPKs), activator protein-1 (AP-1), and nuclear factor-kappaB (NF-kappaB) was
determined by immunoblotting, immunohistochemistry, and electrophoretic mobility
shift assay. We found that EGb inhibited IL-1-induced production of chemokines,
which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated
cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and
release of nitric oxide (NO). The EGb-mediated suppression of the iNOS-NO pathway
correlated with the attenuation of activator protein-1 (AP-1) but not nuclear
factor-kappaB (NF-kappaB) DNA-binding activity. Of the mitogen-activated protein
kinases (MAPKs), EGb inhibited only c-Jun N-terminal kinase (JNK). Unexpectedly,
EGb selectively caused degradation of c-Jun protein. Further investigation
revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c
Jun and could be prevented by the proteosome inhibitor MG-132. The results imply
that EGb protects against chondrocyte degeneration by inhibiting JNK activation
and inducing ubiquitination-dependent c-Jun degradation. Although additional
research is needed, our results suggest that EGb is a potential therapeutic agent
for the treatment of OA.
PMID- 24349177
TI - Effects of 'target' plant species body size on neighbourhood species richness and
composition in old-field vegetation.
AB - Competition is generally regarded as an important force in organizing the
structure of vegetation, and evidence from several experimental studies of
species mixtures suggests that larger mature plant size elicits a competitive
advantage. However, these findings are at odds with the fact that large and small
plant species generally coexist, and relatively smaller species are more common
in virtually all plant communities. Here, we use replicates of ten relatively
large old-field plant species to explore the competitive impact of target
individual size on their surrounding neighbourhoods compared to nearby
neighbourhoods of the same size that are not centred by a large target
individual. While target individuals of the largest of our test species,
Centaurea jacea L., had a strong impact on neighbouring species, in general,
target species size was a weak predictor of the number of other resident species
growing within its immediate neighbourhood, as well as the number of resident
species that were reproductive. Thus, the presence of a large competitor did not
restrict the ability of neighbouring species to reproduce. Lastly, target species
size did not have any impact on the species size structure of neighbouring
species; i.e. they did not restrict smaller, supposedly poorer competitors, from
growing and reproducing close by. Taken together, these results provide no
support for a size-advantage in competition restricting local species richness or
the ability of small species to coexist and successfully reproduce in the
immediate neighbourhood of a large species.
PMID- 24349176
TI - Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in
human urothelial carcinoma cells.
AB - Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in
various malignancies. Here, we sought to clarify the role of autophagy in
celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The
results shows celecoxib induced cellular stress response such as endoplasmic
reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as
autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine
(3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis.
Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated
celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of
autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a
novel therapeutic strategy against UC.
PMID- 24349178
TI - Nephrogenic systemic fibrosis in Denmark--a nationwide investigation.
AB - BACKGROUND: Nephrogenic systemic fibrosis is a debilitating and painful disorder
with an increased stimulation of the connective tissue in the skin and systemic
tissues. The disease is associated with exposure to gadolinium-based contrast
agent used in magnetic resonance imaging in patients with renal impairment.
METHODS: The prevalence of nephrogenic systemic fibrosis has so far never been
determined at a national level. In 2009, Denmark was the first country to design
a guideline for the tracing of nephrogenic systemic fibrosis patients. The aim of
this paper is to communicate the main findings of this quest. RESULTS: The
outcome of the nationwide investigation revealed that Denmark had 65 patients
with nephrogenic systemic fibrosis and thereby the highest prevalence of
nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or
12 per million. CONCLUSIONS: The nationwide investigation in Denmark revealed the
highest prevalence of NSF worldwide. This may be rooted in a high level of
awareness of NSF both among doctors, politicians and, not least, the media,
combined with the fact that a nationwide NSF investigation was initiated.
PMID- 24349179
TI - Effects of ENSO and temporal rainfall variation on the dynamics of successional
communities in old-field succession of a tropical dry forest.
AB - The effects of temporal variation of rainfall on secondary succession of tropical
dry ecosystems are poorly understood. We studied effects of inter-seasonal and
inter-year rainfall variation on the dynamics of regenerative successional
communities of a tropical dry forest in Mexico. We emphasized the effects caused
by the severe El Nino Southern Oscillation (ENSO) occurred in 2005. We
established permanent plots in sites representing a chronosequence of Pasture
(abandoned pastures, 0-1 years fallow age), Early (3-5), Intermediate (8-12), and
Old-Growth Forest categories (n = 3 per category). In total, 8210 shrubs and
trees 10 to 100-cm height were identified, measured, and monitored over four
years. Rates of plant recruitment, growth and mortality, and gain and loss of
species were quantified per season (dry vs. rainy), year, and successional
category, considering whole communities and separating seedlings from sprouts and
shrubs from trees. Community rates changed with rainfall variation without almost
any effect of successional stage. Mortality and species loss rates peaked during
the ENSO year and the following year; however, after two rainy years mortality
peaked in the rainy season. Such changes could result from the severe drought in
the ENSO year, and of the outbreak of biotic agents during the following rainy
years. Growth, recruitment and species gain rates were higher in the rainy season
but they were significantly reduced after the ENSO year. Seedlings exhibited
higher recruitment and mortality rate than sprouts, and shrubs showed higher
recruitment than trees. ENSO strongly impacted both the dynamics and trajectory
of succession, creating transient fluctuations in the abundance and species
richness of the communities. Overall, there was a net decline in plant and
species density in most successional stages along the years. Therefore, strong
drought events have critical consequences for regeneration dynamics, delaying the
successional process and modifying the resilience of these systems.
PMID- 24349180
TI - Testing measurement invariance of the schizotypal personality questionnaire-brief
scores across Spanish and Swiss adolescents.
AB - BACKGROUND: Schizotypy is a complex construct intimately related to psychosis.
Empirical evidence indicates that participants with high scores on schizotypal
self-report are at a heightened risk for the later development of psychotic
disorders. Schizotypal experiences represent the behavioural expression of
liability for psychotic disorders. Previous factorial studies have shown that
schizotypy is a multidimensional construct similar to that found in patients with
schizophrenia. Specifically, using the Schizotypal Personality Questionnaire
Brief (SPQ-B), the three-dimensional model has been widely replicated. However,
there has been no in-depth investigation of whether the dimensional structure
underlying the SPQ-B scores is invariant across countries. METHODS: The main goal
of this study was to examine the measurement invariance of the SPQ-B scores
across Spanish and Swiss adolescents. The final sample was made up of 261 Spanish
participants (51.7% men; M = 16.04 years) and 241 Swiss participants (52.3% men;
M = 15.94 years). RESULTS: The results indicated that Raine et al.'s three-factor
model presented adequate goodness-of-fit indices. Moreover, the results supported
the measurement invariance (configural and partial strong invariance) of the SPQ
B scores across the two samples. Spanish participants scored higher on
Interpersonal dimension than Swiss when latent means were compared. DISCUSSION:
The study of measurement equivalence across countries provides preliminary
evidence for the Raine et al.'s three-factor model and of the cross-cultural
validity of the SPQ-B scores in adolescent population. Future studies should
continue to examine the measurement invariance of the schizotypy and psychosis
risk syndromes across cultures.
PMID- 24349181
TI - Preserved excitatory-inhibitory balance of cortical synaptic inputs following
deprived eye stimulation after a saturating period of monocular deprivation in
rats.
AB - Monocular deprivation (MD) during development leads to a dramatic loss of
responsiveness through the deprived eye in primary visual cortical neurons, and
to degraded spatial vision (amblyopia) in all species tested so far, including
rodents. Such loss of responsiveness is accompanied since the beginning by a
decreased excitatory drive from the thalamo-cortical inputs. However, in the
thalamorecipient layer 4, inhibitory interneurons are initially unaffected by MD
and their synapses onto pyramidal cells potentiate. It remains controversial
whether ocular dominance plasticity similarly or differentially affects the
excitatory and inhibitory synaptic conductances driven by visual stimulation of
the deprived eye and impinging onto visual cortical pyramids, after a saturating
period of MD. To address this issue, we isolated visually-driven excitatory and
inhibitory conductances by in vivo whole-cell recordings from layer 4 regular
spiking neurons in the primary visual cortex (V1) of juvenile rats. We found that
a saturating period of MD comparably reduced visually-driven excitatory and
inhibitory conductances driven by visual stimulation of the deprived eye. Also,
the excitatory and inhibitory conductances underlying the synaptic responses
driven by the ipsilateral, left open eye were similarly potentiated compared to
controls. Multiunit recordings in layer 4 followed by spike sorting indicated
that the suprathreshold loss of responsiveness and the MD-driven ocular
preference shifts were similar for narrow spiking, putative inhibitory neurons
and broad spiking, putative excitatory neurons. Thus, by the time the plastic
response has reached a plateau, inhibitory circuits adjust to preserve the normal
balance between excitation and inhibition in the cortical network of the main
thalamorecipient layer.
PMID- 24349183
TI - Evaluation and ranking of researchers--Bh Index.
AB - Evaluation and ranking of every author is very crucial as it is widely used to
evaluate the performance of the researcher. This article proposes a new method,
called Bh-Index, to evaluate the researchers based on the publications and
citations. The method is built on h-Index and only the h-core articles are taken
into consideration. The method assigns value additions to those articles that
receive significantly high citations in comparison to the h-Index of the
researcher. It provides a wide range of values for a given h-Index and effective
evaluation even for a short period. Use of Bh-Index along with the h-Index gives
a powerful tool to evaluate the researchers.
PMID- 24349182
TI - Geotemporal analysis of Neisseria meningitidis clones in the United States: 2000
2005.
AB - BACKGROUND: The detection of meningococcal outbreaks relies on serogrouping and
epidemiologic definitions. Advances in molecular epidemiology have improved the
ability to distinguish unique Neisseria meningitidis strains, enabling the
classification of isolates into clones. Around 98% of meningococcal cases in the
United States are believed to be sporadic. METHODS: Meningococcal isolates from 9
Active Bacterial Core surveillance sites throughout the United States from 2000
through 2005 were classified according to serogroup, multilocus sequence typing,
and outer membrane protein (porA, porB, and fetA) genotyping. Clones were defined
as isolates that were indistinguishable according to this characterization. Case
data were aggregated to the census tract level and all non-singleton clones were
assessed for non-random spatial and temporal clustering using retrospective space
time analyses with a discrete Poisson probability model. RESULTS: Among 1,062
geocoded cases with available isolates, 438 unique clones were identified, 78 of
which had >=2 isolates. 702 cases were attributable to non-singleton clones,
accounting for 66.0% of all geocoded cases. 32 statistically significant clusters
comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters
had the following attributes: included 2 to 11 cases; 1 day to 33 months
duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per
100,000 population. Serogroups represented among the clusters were: B (n = 12
clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35
cases); 20 clusters (62.5%) were caused by serogroups represented in
meningococcal vaccines that are commercially available in the United States.
CONCLUSIONS: Around 10% of meningococcal disease cases in the U.S. could be
assigned to a geotemporal cluster. Molecular characterization of isolates,
combined with geotemporal analysis, is a useful tool for understanding the spread
of virulent meningococcal clones and patterns of transmission in populations.
PMID- 24349185
TI - A comparison of methods to measure the magnetic moment of magnetotactic bacteria
through analysis of their trajectories in external magnetic fields.
AB - Magnetotactic bacteria possess organelles called magnetosomes that confer a
magnetic moment on the cells, resulting in their partial alignment with external
magnetic fields. Here we show that analysis of the trajectories of cells exposed
to an external magnetic field can be used to measure the average magnetic dipole
moment of a cell population in at least five different ways. We apply this
analysis to movies of Magnetospirillum magneticum AMB-1 cells, and compare the
values of the magnetic moment obtained in this way to that obtained by direct
measurements of magnetosome dimension from electron micrographs. We find that
methods relying on the viscous relaxation of the cell orientation give results
comparable to that obtained by magnetosome measurements, whereas methods relying
on statistical mechanics assumptions give systematically lower values of the
magnetic moment. Since the observed distribution of magnetic moments in the
population is not sufficient to explain this discrepancy, our results suggest
that non-thermal random noise is present in the system, implying that a
magnetotactic bacterial population should not be considered as similar to a
paramagnetic material.
PMID- 24349184
TI - Correlation of cytokine levels and microglial cell infiltration during retinal
degeneration in RCS rats.
AB - Microglial cells, which are immunocompetent cells, are involved in all diseases
of the central nervous system. During their activation in various diseases, a
variety of soluble factors are released. In the present study, the correlation
between cytokine levels and microglial cell migration in the course of retinal
degeneration of Royal College of Surgeons (RCS) rats was evaluated. MFG-E8 and
CD11b were used to confirm the microglial cells. In the retina of RCS rats, the
mRNA expression of seven genes (MFG-E8 and its integrins alphaupsilon and beta5,
CD11b and the cytokines TNF-alpha, IL-1beta, and MCP-1) formed almost similar
bimodal peak distributions, which were centred at P7 and P45 to P60. In contrast,
in rdy rats, which comprised the control group, a unimodal peak distribution
centred at P14 was observed. The gene expression accompanied the activation and
migration of microglial cells from the inner to the outer layer of the retina
during the process of degeneration. Principal component analysis and discriminant
function analysis revealed that the expression of these seven genes, especially
TNF-alpha and CD11b, positively correlated with retinal degeneration and
microglial activity during retinal degeneration in RCS rats, but not in the
control rats. Furthermore, linear regression analysis demonstrated a significant
correlation between the expression of these genes and the activation of
microglial cells in the dystrophic retina. Our findings suggest that the
suppression of microglial cells and the blockade of their cytotoxic effects may
constitute a novel therapeutic strategy for treating photoreceptor death in
various retinal disorders.
PMID- 24349187
TI - Effective classification and gene expression profiling for the
Facioscapulohumeral Muscular Dystrophy.
AB - The Facioscapulohumeral Muscular Dystrophy (FSHD) is an autosomal dominant
neuromuscular disorder whose incidence is estimated in about one in 400,000 to
one in 20,000. No effective therapeutic strategies are known to halt progression
or reverse muscle weakness and atrophy. It is known that the FSHD is caused by
modifications located within a D4ZA repeat array in the chromosome 4q, while
recent advances have linked these modifications to the DUX4 gene. Unfortunately,
the complete mechanisms responsible for the molecular pathogenesis and
progressive muscle weakness still remain unknown. Although there are many studies
addressing cancer databases from a machine learning perspective, there is no such
precedent in the analysis of the FSHD. This study aims to fill this gap by
analyzing two specific FSHD databases. A feature selection algorithm is used as
the main engine to select genes promoting the highest possible classification
capacity. The combination of feature selection and classification aims at
obtaining simple models (in terms of very low numbers of genes) capable of good
generalization, that may be associated with the disease. We show that the
reported method is highly efficient in finding genes to discern between healthy
cases (not affected by the FSHD) and FSHD cases, allowing the discovery of very
parsimonious models that yield negligible repeated cross-validation error. These
models in turn give rise to very simple decision procedures in the form of a
decision tree. Current biological evidence regarding these genes shows that they
are linked to skeletal muscle processes concerning specific human conditions.
PMID- 24349186
TI - Four genotyping schemes for phylogenetic analysis of Pseudomonas aeruginosa:
comparison of their congruence with multi-locus sequence typing.
AB - Several molecular typing schemes have been proposed to differentiate among
isolates and clonal groups, and hence establish epidemiological or phylogenetic
links. It has been widely accepted that multi-locus sequence typing (MLST) is the
gold standard for phylogenetic typing/long-term epidemiological surveillance, but
other recently described methods may be easier to carry out, especially in
settings with limited access to DNA sequencing. Comparing the performance of such
techniques to MLST is therefore of relevance. A study was therefore carried out
with a collection of P. aeruginosa strains (n = 133) typed by four typing
schemes: MLST, multiple-locus variable number tandem repeat analysis (MLVA),
pulsed-field gel electrophoresis (PFGE) and the commercial DiversiLab microbial
typing system (DL). The aim of this study was to compare the results of each
typing method with MLST. The Simpson's indices of diversity were 0.989, 0.980,
0.961 and 0.906 respectively for PFGE, MLVA, DL and MLST. The congruence between
techniques was measured by the adjusted Wallace index (W): this coefficient
indicates the probability that a pair of isolates which is assigned to the same
type by one typing method is also typed as identical by the other. In this
context, the congruence between techniques was recorded as follow: MLVA-type to
predict MLST-type (93%), PFGE to MLST (92%), DL to MLST (64.2%), PFGE to MLVA
(63.5%) and PFGE to DL (61.7%). Conversely, for all above combinations,
prediction was very poor. The congruence was increased at the clonal complex (CC)
level. MLST is regarded the gold standard for phylogenetic classification of
bacteria, but is rather laborious to carry out in many settings. Our data suggest
that MLVA can predict the MLST-type with high accuracy, and even higher when
studying the clonal complex level. Of the studied three techniques MLVA was
therefore the best surrogate method to predict MLST.
PMID- 24349188
TI - Electrical vestibular stimulation after vestibular deafferentation and in
vestibular schwannoma.
AB - BACKGROUND: Vestibular reflexes, evoked by human electrical (galvanic) vestibular
stimulation (EVS), are utilized to assess vestibular function and investigate its
pathways. Our study aimed to investigate the electrically-evoked vestibulo-ocular
reflex (eVOR) output after bilateral and unilateral vestibular deafferentations
to determine the characteristics for interpreting unilateral lesions such as
vestibular schwannomas. METHODS: EVOR was recorded with dual-search coils as
binocular three-dimensional eye movements evoked by bipolar 100 ms-step at EVS
intensities of [0.9, 2.5, 5.0, 7.5, 10.0] mA and unipolar 100 ms-step at 5 mA EVS
intensity. Five bilateral vestibular deafferented (BVD), 12 unilateral vestibular
deafferented (UVD), four unilateral vestibular schwannoma (UVS) patients and 17
healthy subjects were tested with bipolar EVS, and five UVDs with unipolar EVS.
RESULTS: After BVD, bipolar EVS elicited no eVOR. After UVD, bipolar EVS of one
functioning ear elicited bidirectional, excitatory eVOR to cathodal EVS with 9 ms
latency and inhibitory eVOR to anodal EVS, opposite in direction, at half the
amplitude with 12 ms latency, exhibiting an excitatory-inhibitory asymmetry. The
eVOR patterns from UVS were consistent with responses from UVD confirming the
vestibular loss on the lesion side. Unexpectedly, unipolar EVS of the UVD ear,
instead of absent response, evoked one-third the bipolar eVOR while unipolar EVS
of the functioning ear evoked half the bipolar response. CONCLUSIONS: The
bidirectional eVOR evoked by bipolar EVS from UVD with an excitatory-inhibitory
asymmetry and the 3 ms latency difference between normal and lesion side may be
useful for detecting vestibular lesions such as UVS. We suggest that current
spread could account for the small eVOR to 5 mA unipolar EVS of the UVD ear.
PMID- 24349189
TI - Dendritic branch intersections are structurally regulated targets for efficient
axonal wiring and synaptic clustering.
AB - Synaptic clustering on dendritic branches enhances plasticity, input integration
and neuronal firing. However, the mechanisms guiding axons to cluster synapses at
appropriate sites along dendritic branches are poorly understood. We searched for
such a mechanism by investigating the structural overlap between dendritic
branches and axons in a simplified model of neuronal networks--the hippocampal
cell culture. Using newly developed software, we converted images of meshes of
overlapping axonal and dendrites into topological maps of intersections, enabling
quantitative study of overlapping neuritic geometry at the resolution of single
dendritic branch-to-branch and axon-to-branch crossings. Among dendro-dendritic
crossing configurations, it was revealed that the orientations through which
dendritic branches cross is a regulated attribute. While crossing angle
distribution among branches thinner than 1 um appeared to be random, dendritic
branches 1 um or wider showed a preference for crossing each other at angle
ranges of either 50 degrees -70 degrees or 80 degrees -90 degrees . It was then
found that the dendro-dendritic crossings themselves, as well as their selective
angles, both affected the path of axonal growth. Axons displayed 4 fold stronger
tendency to traverse within 2 um of dendro-dendritic intersections than at
farther distances, probably to minimize wiring length. Moreover, almost 70% of
the 50 degrees -70 degrees dendro-denritic crossings were traversed by axons
from the obtuse angle's zone, whereas only 15% traversed through the acute
angle's zone. By contrast, axons showed no orientation restriction when
traversing 80 degrees -90 degrees crossings. When such traverse behavior was
repeated by many axons, they converged in the vicinity of dendro-dendritic
intersections, thereby clustering their synaptic connections. Thus, the vicinity
of dendritic branch-to-branch crossings appears to be a regulated structure used
by axons as a target for efficient wiring and as a preferred site for synaptic
clustering. This synaptic clustering mechanism may enhance synaptic co-activity
and plasticity.
PMID- 24349190
TI - Is Switzerland suitable for the invasion of Aedes albopictus [corrected]?
AB - BACKGROUND: Over the last 30 years, the Asian tiger mosquito, Aedes albopictus,
has rapidly spread around the world. The European distribution comprises the
Mediterranean basin with a first appearance in Switzerland in 2003. Early
identification of the most suitable areas in Switzerland allowing progressive
invasion by this species is considered crucial to suggest adequate surveillance
and control plans. METHODOLOGY/PRINCIPAL FINDINGS: We identified the most
suitable areas for invasion and establishment of Ae. albopictus in Switzerland.
The potential distribution areas linked to the current climatic suitability were
assessed using remotely sensed land surface temperature data recorded by the
MODIS satellite sensors. Suitable areas for adult survival and overwintering of
diapausing eggs were also identified for future climatic conditions, considering
two different climate change scenarios (A1B, A2) for the periods 2020-2049 and
2045-2074. At present, the areas around Lake Geneva in western Switzerland
provide suitable climatic conditions for Ae. albopictus. In northern Switzerland,
parts of the Rhine valley, around Lake Constance, as well as the surroundings of
Lake Neuchatel, appear to be suitable for the survival at least of adult Ae.
albopictus. However, these areas are characterized by winters currently being too
cold for survival and development of diapausing eggs. In southern Switzerland,
Ae. albopictus is already well-established, especially in the Canton of Ticino.
For the years 2020-2049, the predicted possible spread of the tiger mosquito does
not differ significantly from its potential current distribution. However,
important expansions are obtained if the period is extended to the years 2045
2074, when Ae. albopictus may invade large new areas. CONCLUSIONS/SIGNIFICANCE:
Several parts of Switzerland provide suitable climatic conditions for invasion
and establishment of Ae. albopictus. The current distribution and rapid spread in
other European countries suggest that the tiger mosquito will colonize new areas
in Switzerland in the near future.
PMID- 24349191
TI - Risk of obstructive sleep apnea in Parkinson's disease: a meta-analysis.
AB - STUDY OBJECTIVES: Sleep disorders are a common symptom of Parkinson's disease
(PD) and they significantly impair the sleep quality of the PD patients. However,
there is no conclusive evidence to support the relation between PD and the
prevalence of obstructive sleep apnea (OSA). The purpose of this meta-analysis
review is to evaluate the association between PD and the prevalence of OSA.
METHODS: A comprehensive literature search was conducted on PubMed and Embase
through July 2013. Only studies that referred to PD and the prevalence of OSA and
that met the selection criteria were included in the analysis. The odds ratios
(ORs) were used to evaluate the relationship of PD and the prevalence of OSA by
the fixed-effect model. RESULTS: Five eligible studies were analyzed in this
study including 322 cases and 6,361 controls. The pooled-analysis showed the OR
to be 0.60 (95% confidence interval (CI): 0.44 to 0.81, P = 0.001) and I(2) =
0.0% (chi(2) = 3.90, P = 0.420) in the fixed-effect model. CONCLUSIONS: Although
we only included five small sample studies that indicated high homogeneity in the
heterogeneity test, the results suggest that there is a significant negative
association between PD and the prevalence of OSA; PD patients generally have a
reduced prevalence of OSA. According to our analysis, these results are primarily
due to the lower BMI of PD patients when compared with the general population
controls.
PMID- 24349192
TI - Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving
complement component 4.
AB - BACKGROUND: It has been hypothesized that persistent hepatitis C virus (HCV)
infection is mediated in part by viral proteins that abrogate the host immune
response, including the complement system, but the precise mechanisms are not
well understood. We investigated whether HCV proteins are involved in the
fragmentation of complement component 4 (C4), composed of subunits C4alpha,
C4beta, and C4gamma, and the role of HCV proteins in complement activation.
METHODS: Human C4 was incubated with HCV nonstructural (NS) 3/4A protease, core,
or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis and then subjected to peptide sequencing. The activity of the
classical complement pathway was examined using an erythrocyte hemolysis assay.
The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells,
respectively, was also examined. RESULTS: HCV NS3/4A protease cleaved C4gamma in
a concentration-dependent manner, but viral core and NS5 did not. A specific
inhibitor of NS3/4A protease reduced C4gamma cleavage. NS3/4A protease-mediated
cleavage of C4 inhibited classical pathway activation, which was abrogated by a
NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild
type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4gamma
fragments. Such C4 processing, with a concomitant reduction in levels of full
length C4gamma, was also observed in HCV-infected cells expressing C4.
CONCLUSIONS: C4 is a novel cellular substrate of the HCV NS3/4A protease.
Understanding disturbances in the complement system mediated by NS3/4A protease
may provide new insights into the mechanisms underlying persistent HCV infection.
PMID- 24349193
TI - Simultaneous in vitro characterisation of DNA deaminase function and associated
DNA repair pathways.
AB - During immunoglobulin (Ig) diversification, activation-induced deaminase (AID)
initiates somatic hypermutation and class switch recombination by catalysing the
conversion of cytosine to uracil. The synergy between AID and DNA repair pathways
is fundamental for the introduction of mutations, however the molecular and
biochemical mechanisms underlying this process are not fully elucidated. We
describe a novel method to efficiently decipher the composition and activity of
DNA repair pathways that are activated by AID-induced lesions. The in vitro
resolution (IVR) assay combines AID based deamination and DNA repair activities
from a cellular milieu in a single assay, thus avoiding synthetically created DNA
lesions or genetic-based readouts. Recombinant GAL4-AID fusion protein is
targeted to a plasmid containing GAL4 binding sites, allowing for controlled
cytosine deamination within a substrate plasmid. Subsequently, the Xenopus laevis
egg extract provides a source of DNA repair proteins and functional repair
pathways. Our results demonstrated that DNA repair pathways which are in vitro
activated by AID-induced lesions are reminiscent of those found during AID
induced in vivo Ig diversification. The comparative ease of manipulation of this
in vitro systems provides a new approach to dissect the complex DNA repair
pathways acting on defined physiologically lesions, can be adapted to use with
other DNA damaging proteins (e.g. APOBECs), and provide a means to develop and
characterise pharmacological agents to inhibit these potentially oncogenic
processes.
PMID- 24349194
TI - Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in
human subcutaneous adipocytes and 3T3-L1 cells.
AB - Current evidence indicates that chemical pollutants may interfere with the
homeostatic control of nutrient metabolism, thereby contributing to the increased
prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound
contained in plastic which is considered a candidate for impairing energy and
glucose metabolism. We have investigated the impact of low doses of BPA on
adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose
tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to
evaluate the effect on glucose utilization, insulin sensitivity and cytokine
secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulated
glucose utilization, without grossly interfering with adipocyte differentiation.
Accordingly, mRNA levels of the adipogenic markers PPARgamma and GLUT4 were
unchanged upon BPA exposure. BPA treatment also impaired insulin-activated
receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA
was accompanied by increased release of IL-6 and IFN-gamma, as assessed by
multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways.
Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA
effect on insulin signaling and glucose utilization. In conclusion, low doses of
BPA interfere with inflammatory/insulin signaling pathways, leading to impairment
of adipose cell function.
PMID- 24349195
TI - An internal ribosome entry site (IRES) mutant library for tuning expression level
of multiple genes in mammalian cells.
AB - A set of mutated Encephalomyocarditis virus (EMCV) internal ribosome entry site
(IRES) elements with varying strengths is generated by mutating the translation
initiation codons of 10(th), 11(th), and 12(th) AUG to non-AUG triplets. They are
able to control the relative expression of multiple genes over a wide range in
mammalian cells in both transient and stable transfections. The relative strength
of each IRES mutant remains similar in different mammalian cell lines and is not
gene specific. The expressed proteins have correct molecular weights.
Optimization of light chain over heavy chain expression by these IRES mutants
enhances monoclonal antibody expression level and quality in stable
transfections. Uses of this set of IRES mutants can be extended to other
applications such as synthetic biology, investigating interactions between
proteins and its complexes, cell engineering, multi-subunit protein production,
gene therapy, and reprogramming of somatic cells into stem cells.
PMID- 24349196
TI - Caveolin-1--a novel interacting partner of organic cation/carnitine transporter
(Octn2): effect of protein kinase C on this interaction in rat astrocytes.
AB - OCTN2--the Organic Cation Transporter Novel family member 2 (SLC22A5) is known to
be a xenobiotic/drug transporter. It transports as well carnitine--a compound
necessary for oxidation of fatty acids and mutations of its gene cause primary
carnitine deficiency. Octn2 regulation by protein kinase C (PKC) was studied in
rat astrocytes--cells in which beta-oxidation takes place in the brain.
Activation of PKC with phorbol ester stimulated L-carnitine transport and
increased cell surface presence of the transporter, although no PKC-specific
phosphorylation of Octn2 could be detected. PKC activation resulted in an
augmented Octn2 presence in cholesterol/sphingolipid-rich microdomains of plasma
membrane (rafts) and increased co-precipitation of Octn2 with raft-proteins,
caveolin-1 and flotillin-1. Deletion of potential caveolin-1 binding motifs
pointed to amino acids 14-22 and 447-454 as the caveolin-1 binding sites within
Octn2 sequence. A direct interaction of Octn2 with caveolin-1 in astrocytes upon
PKC activation was detected by proximity ligation assay, while such an
interaction was excluded in case of flotillin-1. Functioning of a multi-protein
complex regulated by PKC has been postulated in rOctn2 trafficking to the cell
surface, a process which could be important both under physiological conditions,
when carnitine facilitates fatty acids catabolism and controls free Coenzyme A
pool as well as in pathology, when transport of several drugs can induce
secondary carnitine deficiency.
PMID- 24349197
TI - Meta-analysis of long-term vitamin D supplementation on overall mortality.
AB - INTRODUCTION: It has been suggested that vitamin D is effective to prevent
mortality. However, there is no consistent conclusion that the effects of vitamin
D supplementation on all-cause mortality are associated with duration of
treatment. We conducted a meta-analysis regarding this issue in an effort to
provide a more robust answer. METHODS: A comprehensive search in a number of
databases, including MEDLINE, Embase and The Cochrane Central Register of
Controlled Trials, was conducted for collecting randomized controlled trials
(RCTs) on vitamin D supplementation preventing mortality. Two investigators
independently screened the literature according to the inclusive and exclusive
criteria and the relative data were extracted. Data analysis was performed by
using Review Manager 5.0 software. RESULTS: Data from forty-two RCT s were
included. Vitamin D therapy significantly decreased all-cause mortality with a
duration of follow-up longer than 3 years with a RR (95% CI) of 0.94 (0.90-0.98).
No benefit was seen in a shorter follow-up periods with a RR (95% CI) of 1.04
(0.97-1.12). Results remain robust after sensitivity analysis. The following
subgroups of long-term follow-up had significantly fewer deaths: female only,
participants with a mean age younger than 80, daily dose of 800 IU or less,
participants with vitamin D insufficiency (baseline 25-hydroxyvitamin D level
less than 50 nmol/L) and cholecalciferol therapy. In addition, the combination of
vitamin D and calcium significantly reduced mortality and vitamin D alone also
had a trend to decrease mortality in a longer time follow up. CONCLUSIONS: The
data suggest that supplementation of vitamin D is effective in preventing overall
mortality in a long-term treatment, whereas it is not significantly effective in
a treatment duration shorter than 3 years. Future studies are needed to identify
the efficacy of vitamin D on specific mortality, such as cancer and
cardiovascular disease mortality in a long-term treatment duration.
PMID- 24349198
TI - Dynamics and flexibility of human aromatase probed by FTIR and time resolved
fluorescence spectroscopy.
AB - Human aromatase (CYP19A1) is a steroidogenic cytochrome P450 converting androgens
into estrogens. No ligand-free crystal structure of the enzyme is available to
date. The crystal structure in complex with the substrate androstenedione and the
steroidal inhibitor exemestane shows a very compact conformation of the enzyme,
leaving unanswered questions on the conformational changes that must occur to
allow access of the ligand to the active site. As H/D exchange kinetics followed
by FTIR spectroscopy can provide information on the conformational changes in
proteins where solvent accessibility is affected, here the amide I region was
used to measure the exchange rates of the different elements of the secondary
structure for aromatase in the ligand-free form and in the presence of the
substrate androstenedione and the inhibitor anastrozole. Biphasic exponential
functions were found to fit the H/D exchange data collected as a function of
time. Two exchange rates were assigned to two populations of protons present in
different flexible regions of the protein. The addition of the substrate
androstenedione and the inhibitor anastrozole lowers the H/D exchange rates of
the alpha-helices of the enzyme when compared to the ligand-free form.
Furthermore, the presence of the inhibitor anastrozole lowers exchange rate
constant (k1) for beta-sheets from 0.22+/-0.06 min(-1) for the inhibitor-bound
enzyme to 0.12+/-0.02 min(-1) for the free protein. Dynamics effects localised in
helix F were studied by time resolved fluorescence. The data demonstrate that the
fluorescence lifetime component associated to Trp224 emission undergoes a shift
toward longer lifetimes (from ~5.0 to ~5.5 ns) when the substrate or the
inhibitor are present, suggesting slower dynamics in the presence of ligands.
Together the results are consistent with different degrees of flexibility of the
access channel and therefore different conformations adopted by the enzyme in the
free, substrate- and inhibitor-bound forms.
PMID- 24349199
TI - A prognostic gene signature for metastasis-free survival of triple negative
breast cancer patients.
AB - Although triple negative breast cancers (TNBC) are the most aggressive subtype of
breast cancer, they currently lack targeted therapies. Because this
classification still includes a heterogeneous collection of tumors, new tools to
classify TNBCs are urgently required in order to improve our prognostic
capability for high risk patients and predict response to therapy. We previously
defined a gene expression signature, RKIP Pathway Metastasis Signature (RPMS),
based upon a metastasis-suppressive signaling pathway initiated by Raf Kinase
Inhibitory Protein (RKIP). We have now generated a new BACH1 Pathway Metastasis
gene signature (BPMS) that utilizes targets of the metastasis regulator BACH1.
Specifically, we substituted experimentally validated target genes to generate a
new BACH1 metagene, developed an approach to optimize patient tumor
stratification, and reduced the number of signature genes to 30. The BPMS
significantly and selectively stratified metastasis-free survival in basal-like
and, in particular, TNBC patients. In addition, the BPMS further stratified
patients identified as having a good or poor prognosis by other signatures
including the Mammaprint(r) and Oncotype(r) clinical tests. The BPMS is thus
complementary to existing signatures and is a prognostic tool for high risk ER
HER2- patients. We also demonstrate the potential clinical applicability of the
BPMS as a single sample predictor. Together, these results reveal the potential
of this pathway-based BPMS gene signature to identify high risk TNBC patients
that can respond effectively to targeted therapy, and highlight BPMS genes as
novel drug targets for therapeutic development.
PMID- 24349200
TI - The 12 item Social and Economic Conservatism Scale (SECS).
AB - Recent years have seen a surge in psychological research on the relationship
between political ideology (particularly conservatism) and cognition, affect,
behaviour, and even biology. Despite this flurry of investigation, however, there
is as yet no accepted, validated, and widely used multi-item scale of
conservatism that is concise, that is modern in its conceptualisation, and that
includes both social and economic conservatism subscales. In this paper the 12
Item Social and Economic Conservatism Scale (SECS) is proposed and validated to
help fill this gap. The SECS is suggested to be an important and useful tool for
researchers working in political psychology.
PMID- 24349201
TI - NEXN is a novel susceptibility gene for coronary artery disease in Han Chinese.
AB - Coronary artery disease (CAD) is the leading cause of death and disability in the
world. Genome-wide association studies have implicated the importance of the
genetic contribution of vascular smooth muscle cells (VSMCs) function in CAD
susceptibility. The aberrant phenotypic modulation of VSMC is responsible for the
pathological vascular intima hyperplasia that is the hallmark for atherosclerotic
morphology. NEXN is a muscle-specific F-actin binding protein and is regulated by
inflammatory cytokines in VSMCs. Whether NEXN contributes to human vascular
disorders is still unknown. In this study, we genotyped 5 SNPs, tagging all of
the 17 common SNPs within 54 kilobases (kb) covering NEXN gene and its flanking
region, in 1883 patients with CAD and 1973 healthy individuals from Han Chinese,
and identified one SNP, rs1780050, which was strongly associated with CAD trait.
The Bonferroni corrected P-value was 7.65*10(-5). The odds ratio (95% confidence
interval) was 1.23 (1.12-1.36) with statistical power of 0.994. Functional
analysis showed that NEXN promotes VSMC to a contractile phenotype in vitro and
inhibits balloon-injury induced neointima formation in vivo. Further eQTL
analysis demonstrated that the risk allele T of rs1780050 is associated with
decreased expression of NEXN, thus contributing to a higher risk of CAD
susceptibility in the population. This is, to our knowledge, the first study to
identify NEXN as a novel CAD susceptibility gene with both genetic and functional
evidence.
PMID- 24349202
TI - Spatiotemporal analysis of predation by carabid beetles (Carabidae) on nematode
infected and uninfected slugs in the field.
AB - The dynamics of predation on parasites within prey has received relatively little
attention despite the profound effects this is likely to have on both prey and
parasite numbers and hence on biological control programmes where parasites are
employed. The nematode Phasmarhabditis hermaphrodita is a commercially available
biological agent against slugs. Predation on these slugs may, at the same time,
result in intraguild predation on slug-parasitic nematodes. This study describes,
for the first time, predation by carabid beetles on slugs and their nematode
parasites on both spatial and temporal scales, using PCR-based methods. The
highest nematode infection levels were found in the slugs Deroceras reticulatum
and Arion silvaticus. Numbers of infected slugs decreased over time and no
infected slugs were found four months after nematode application. The density of
the most abundant slug, the invasive Arion vulgaris, was positively related to
the activity-density of the carabid beetle, Carabus nemoralis. Predation on slugs
was density and size related, with highest predation levels also on A. vulgaris.
Predation on A. vulgaris decreased significantly in summer when these slugs were
larger than one gram. Predation by C. nemoralis on slugs was opportunistic,
without any preferences for specific species. Intraguild predation on the
nematodes was low, suggesting that carabid beetles such as C. nemoralis probably
do not have a significant impact on the success of biological control using P.
hermaphrodita.
PMID- 24349203
TI - Skeletal cell differentiation is enhanced by atmospheric dielectric barrier
discharge plasma treatment.
AB - Enhancing chondrogenic and osteogenic differentiation is of paramount importance
in providing effective regenerative therapies and improving the rate of fracture
healing. This study investigated the potential of non-thermal atmospheric
dielectric barrier discharge plasma (NT-plasma) to enhance chondrocyte and
osteoblast proliferation and differentiation. Although the exact mechanism by
which NT-plasma interacts with cells is undefined, it is known that during
treatment the atmosphere is ionized generating extracellular reactive oxygen and
nitrogen species (ROS and RNS) and an electric field. Appropriate NT-plasma
conditions were determined using lactate-dehydrogenase release, flow cytometric
live/dead assay, flow cytometric cell cycle analysis, and Western blots to
evaluate DNA damage and mitochondrial integrity. We observed that specific NT
plasma conditions were required to prevent cell death, and that loss of pre
osteoblastic cell viability was dependent on intracellular ROS and RNS
production. To further investigate the involvement of intracellular ROS,
fluorescent intracellular dyes Mitosox (superoxide) and dihydrorhodamine
(peroxide) were used to assess onset and duration after NT-plasma treatment. Both
intracellular superoxide and peroxide were found to increase immediately post NT
plasma treatment. These increases were sustained for one hour but returned to
control levels by 24 hr. Using the same treatment conditions, osteogenic
differentiation by NT-plasma was assessed and compared to peroxide or osteogenic
media containing beta-glycerolphosphate. Although both NT-plasma and peroxide
induced differentiation-specific gene expression, neither was as effective as the
osteogenic media. However, treatment of cells with NT-plasma after 24 hr in
osteogenic or chondrogenic media significantly enhanced differentiation as
compared to differentiation media alone. The results of this study show that NT
plasma can selectively initiate and amplify ROS signaling to enhance
differentiation, and suggest this technology could be used to enhance bone fusion
and improve healing after skeletal injury.
PMID- 24349204
TI - Variation in yield gap induced by nitrogen, phosphorus and potassium fertilizer
in North China Plain.
AB - A field experiment was conducted under a wheat-maize rotation system from 1990 to
2006 in North China Plain (NCP) to determine the effects of N, P and K on yield
and yield gap. There were five treatments: NPK, PK, NK, NP and a control. Average
wheat and maize yields were the highest in the NPK treatment, followed by those
in the NP plots among all treatments. For wheat and maize yield, a significant
increasing trend over time was found in the NPK-treated plots and a decreasing
trend in the NK-treated plots. In the absence of N or P, wheat and maize yields
were significantly lower than those in the NPK treatment. For both crops, the
increasing rate of the yield gap was the highest in the P omission plots, i.e.,
189.1 kg ha(-1) yr(-1) for wheat and 560.6 kg ha(-1) yr(-1) for maize. The
cumulative omission of P fertilizer induced a deficit in the soil available N and
extractable P concentrations for maize. The P fertilizer was more pivotal in long
term wheat and maize growth and soil fertility conservation in NCP, although the
N fertilizer input was important for both crops growth. The crop response to K
fertilizers was much lower than that to N or P fertilizers, but for maize, the
cumulative omission of K fertilizer decreased the yield by 26% and increased the
yield gap at a rate of 322.7 kg ha(-1) yr(-1). The soil indigenous K supply was
not sufficiently high to meet maize K requirement over a long period. The proper
application of K fertilizers is necessary for maize production in the region.
Thus, the appropriate application of N and P fertilizers for the growth of both
crops, while regularly combining K fertilizers for maize growth, is absolutely
necessary for sustainable crop production in the NCP.
PMID- 24349205
TI - Association between oral health status and type 2 diabetes mellitus among
Sudanese adults: a matched case-control study.
AB - AIM: The purpose of this study was to compare the clinical and subjective oral
health indicators of type 2 diabetic patients (T2DM) with age and gender matched
non-diabetic controls. A second aim was to identify clinical and subjective oral
health indicators that discriminate between well-controlled and poorly controlled
T2DM patients as well as between patients with long and short duration of the
disease. METHODS: A total of 457 individuals participated in the study (154 T2DM
cases and 303 non-diabetic controls). The T2DM group was sub-divided according to
metabolic control [(well-controlled: glycosylated haemoglobin test 8%), (poorly
controlled: glycosylated haemoglobin test > 8%)] and according to duration of
T2DM [(long duration: >10 years), (short duration: 10 years)]. Participants were
interviewed using a structured questionnaire including socio-demographics,
lifestyle and oral health related quality of life factors. The clinical
examination comprised full mouth probing depths, plaque index, tooth mobility
index, furcation involvement and coronal and root surface caries. RESULTS: The
T2DM patients presented with more probing depths 4 mm, furcation involvement,
tooth mobility, missing teeth, and oral impacts on daily performance (OIDP). The
corresponding adjusted odds ratios and their 95% confidence intervals were 4.07
(1.74-9.49), 2.96 (1.36-6.45), 5.90 (2.26-15.39), 0.23 (0.08-0.63) and 3.46 (1.61
7.42), respectively. Moreover, the odds ratio was 2.60 (1.21-5.55) for the poorly
controlled T2DM patients to have high levels of mobility index and 2.94 (1.24
6.94) for those with long duration of T2DM to have high decayed, missed and
filled teeth (DMFT) values. CONCLUSION: This study revealed that chronic
periodontitis, tooth mobility, furcation involvement and OIDP were more prevalent
among T2DM patients compared to their non-diabetic controls.
PMID- 24349207
TI - Dynamic source routing strategy for two-level flows on scale-free networks.
AB - Packets transmitting in real communication networks such as the Internet can be
classified as time-sensitive or time-insensitive. To better support the real-time
and time-insensitive applications, we propose a two-level flow traffic model in
which packets are labeled as level-1 or level-2, and those with level-1 have
higher priority to be transmitted. In order to enhance the traffic capacity of
the two-level flow traffic model, we expand the global dynamic routing strategy
and propose a new dynamic source routing which supports no routing-flaps, high
traffic capacity, and diverse traffic flows. As shown in this paper, the proposed
dynamic source routing can significantly enhance the traffic capacity and quality
of time-sensitive applications compared with the global shortest path routing
strategy.
PMID- 24349206
TI - The transcriptomic response of rat hepatic stellate cells to endotoxin:
implications for hepatic inflammation and immune regulation.
AB - With their location in the perisinusoidal space of Disse, hepatic stellate cells
(HSCs) communicate with all of the liver cell types both by physical association
(cell body as well as cytosolic processes penetrating into sinusoids through the
endothelial fenestrations) and by producing several cytokines and chemokines.
Bacterial lipopolysaccharide (LPS), circulating levels of which are elevated in
liver diseases and transplantation, stimulates HSCs to produce increased amounts
of cytokines and chemokines. Although recent research provides strong evidence
for the role of HSCs in hepatic inflammation and immune regulation, the number of
HSC-elaborated inflammatory and immune regulatory molecules may be much greater
then known at the present time. Here we report time-dependent changes in the gene
expression profile of inflammatory and immune-regulatory molecules in LPS
stimulated rat HSCs, and their validation by biochemical analyses. LPS strongly
up-regulated LPS-response elements (TLR2 and TLR7) but did not affect TLR4 and
down-regulated TLR9. LPS also up-regulated genes in the MAPK, NFkappaB, STAT,
SOCS, IRAK and interferon signaling pathways, numerous CC and CXC chemokines and
IL17F. Interestingly, LPS modulated genes related to TGFbeta and HSC activation
in a manner that would limit their activation and fibrogenic activity. The data
indicate that LPS-stimulated HSCs become a major cell type in regulating hepatic
inflammatory and immunological responses by altering expression of numerous
relevant genes, and thus play a prominent role in hepatic pathophysiology
including liver diseases and transplantation.
PMID- 24349209
TI - A quantitative framework for flower phenotyping in cultivated carnation (Dianthus
caryophyllus L.).
AB - Most important breeding goals in ornamental crops are plant appearance and flower
characteristics where selection is visually performed on direct offspring of
crossings. We developed an image analysis toolbox for the acquisition of flower
and petal images from cultivated carnation (Dianthus caryophyllus L.) that was
validated by a detailed analysis of flower and petal size and shape in 78
commercial cultivars of D. caryophyllus, including 55 standard, 22 spray and 1
pot carnation cultivars. Correlation analyses allowed us to reduce the number of
parameters accounting for the observed variation in flower and petal morphology.
Convexity was used as a descriptor for the level of serration in flowers and
petals. We used a landmark-based approach that allowed us to identify eight main
principal components (PCs) accounting for most of the variance observed in petal
shape. The effect and the strength of these PCs in standard and spray carnation
cultivars are consistent with shared underlying mechanisms involved in the
morphological diversification of petals in both subpopulations. Our results also
indicate that neighbor-joining trees built with morphological data might infer
certain phylogenetic relationships among carnation cultivars. Based on estimated
broad-sense heritability values for some flower and petal features, different
genetic determinants shall modulate the responses of flower and petal morphology
to environmental cues in this species. We believe our image analysis toolbox
could allow capturing flower variation in other species of high ornamental value.
PMID- 24349208
TI - Hepatic crown-like structure: a unique histological feature in non-alcoholic
steatohepatitis in mice and humans.
AB - Although macrophages are thought to be crucial for the pathogenesis of chronic
inflammatory diseases, how they are involved in disease progression from simple
steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we
report the unique histological structure termed "hepatic crown-like structures
(hCLS)" in the mouse model of human NASH; melanocortin-4 receptor deficient mice
fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround
hepatocytes with large lipid droplets, which is similar to those described in
obese adipose tissue. Histological analysis revealed that hCLS is closely
associated with activated fibroblasts and collagen deposition. When treatment
with clodronate liposomes effectively depletes macrophages scattered in the
liver, with those in hCLS intact, hepatic expression of inflammatory and
fibrogenic genes is unaffected, suggesting that hCLS is an important source of
inflammation and fibrosis during the progression of NASH. Notably, the number of
hCLS is positively correlated with the extent of liver fibrosis. We also observed
increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH
patients. Collectively, our data provide evidence that hCLS is involved in the
development of hepatic inflammation and fibrosis, thereby suggesting its
pathophysiologic role in disease progression from simple steatosis to NASH.
PMID- 24349210
TI - YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis.
AB - MIA/CD-RAP is a small, secreted protein involved in cartilage differentiation and
melanoma progression. We recently revealed that p54(nrb) acts as a mediator of
MIA/CD-RAP action to promote chondrogenesis and the progression of malignant
melanoma. As the molecular mechanism of MIA/CD-RAP action in cartilage has not
been defined in detail until now, we aimed to understand the regulation of
p54(nrb) transcription in chondrogenesis. We concentrated on the previously
described MIA/CD-RAP-dependent regulatory region in the p54(nrb) promoter and
characterized the transcriptional regulation of p54(nrb) by MIA/CD-RAP in
cartilage. A series of truncated p54(nrb) promoter constructs and mutagenesis
analysis revealed that the transcription factor YBX1, which has not been
investigated in chondrogenesis thus far, is the mediator of MIA/CD-RAP dependent
activation of p54(nrb) transcription. A systematic analysis of genes carrying
this binding site in their promoter region revealed further potential MIA/CD-RAP
regulated genes that have been implicated in cartilage differentiation. In
summary, we described the effects of MIA/CD-RAP on transcriptional regulation in
chondrocytes. Understanding the regulation of p54(nrb) via YBX1 contributes to
the understanding of chondrogenesis. Uncovering new downstream effectors that
function via the activation of YBX1 supports the important role of MIA/CD-RAP in
these processes.
PMID- 24349211
TI - Common neural mechanisms underlying reversal learning by reward and punishment.
AB - Impairments in flexible goal-directed decisions, often examined by reversal
learning, are associated with behavioral abnormalities characterized by
impulsiveness and disinhibition. Although the lateral orbital frontal cortex
(OFC) has been consistently implicated in reversal learning, it is still unclear
whether this region is involved in negative feedback processing, behavioral
control, or both, and whether reward and punishment might have different effects
on lateral OFC involvement. Using a relatively large sample (N = 47), and a
categorical learning task with either monetary reward or moderate electric shock
as feedback, we found overlapping activations in the right lateral OFC (and
adjacent insula) for reward and punishment reversal learning when comparing
correct reversal trials with correct acquisition trials, whereas we found
overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when
negative feedback signaled contingency change. The right lateral OFC and DLPFC
also showed greater sensitivity to punishment than did their left homologues,
indicating an asymmetry in how punishment is processed. We propose that the right
lateral OFC and anterior insula are important for transforming affective feedback
to behavioral adjustment, whereas the right DLPFC is involved in higher level
attention control. These results provide insight into the neural mechanisms of
reversal learning and behavioral flexibility, which can be leveraged to
understand risky behaviors among vulnerable populations.
PMID- 24349212
TI - In vivo and in vitro characterization of the immune stimulating activity of the
Neisserial porin PorB.
AB - Vaccines play a vital role in modern medicine. The development of novel vaccines
for emerging and resistant pathogens has been aided in recent years by the use of
novel adjuvants in subunit vaccines. A deeper understanding of the molecular
pathways behind adjuvanticity is required to better select immunostimulatory
molecules for use in individual vaccines. To this end, we have undertaken a study
of the essential signaling pathways involved in the innate and adaptive immune
responses to the Neisseria meningitidis outer membrane protein Porin B (PorB). We
have previously demonstrated that PorB is an agonist of Toll-Like Receptor 2
(TLR2) and acts as an adjuvant in vaccines for protein, carbohydrate and
lipopolysaccharide antigens using murine models. Here we demonstrate NFkappaB
translocation following stimulation with PorB only occurs in the presence of
TLR2. IL-6 and TNF-alpha secretion was shown to be MAPK dependent. Surface
expression of activation markers on macrophages, including CD40, CD69, and CD86,
was increased following PorB stimulation in vitro. Interestingly, some
upregulation of CD54 and CD69 was still observed in macrophages obtained from
TLR2 KO mice, indicating a possible non-TLR2 mediated activation pathway induced
by PorB. In a murine vaccination model, using ovalbumin as the antigen and PorB
as the adjuvant, a decreased antigen-specific IgG production was observed in TLR2
KO mice; adjuvant-dependent increased IgG production was entirely ablated in
MyD88 KO mice. These observations demonstrate the importance of the above
pathways to the adjuvant activity of PorB. The potential TLR2 independent effect
is currently being explored.
PMID- 24349213
TI - The microenvironment-specific transformation of adult stem cells models malignant
triton tumors.
AB - Here, we demonstrated the differentiation potential of murine muscle-derived
stem/progenitor cells (MDSPCs) toward myogenic, neuronal, and glial lineages.
MDSPCs, following transplantation into a critical-sized sciatic nerve defect in
mice, showed full regeneration with complete functional recovery of the injured
peripheral nerve at 6 weeks post-implantation. However, several weeks after
regeneration of the sciatic nerve, neoplastic growths were observed. The
resulting tumors were malignant peripheral nerve sheath tumors (MPNSTs) with
rhabdomyoblastic differentiation, expressing myogenic, neurogenic, and glial
markers, common markers of human malignant triton tumors (MTTs). No signs of
tumorigenesis were observed 17 weeks post-implantation of MDSPCs into the
gastrocnemius muscles of dystrophic/mdx mice, or 1 year following subcutaneous or
intravenous injection. While MDSPCs were not oncogenic in nature, the neoplasias
were composed almost entirely of donor cells. Furthermore, cells isolated from
the tumors were serially transplantable, generating tumors when reimplanted into
mice. However, this transformation could be abrogated by differentiation of the
cells toward the neurogenic lineage prior to implantation. These results
establish that MDSPCs participated in the regeneration of the injured peripheral
nerve but transformed in a microenvironment- and time-dependent manner, when they
likely received concomitant neurogenic and myogenic differentiation signals. This
microenvironment-specific transformation provides a useful mouse model for human
MTTs and potentially some insight into the origins of this disease.
PMID- 24349214
TI - A leaderless genome identified during persistent bovine coronavirus infection is
associated with attenuation of gene expression.
AB - The establishment of persistent viral infection is often associated with the
selection of one or more mutant viruses. For example, it has been found that an
intraleader open reading frame (ORF) in genomic and subgenomic mRNA (sgmRNA)
molecules is selected during bovine coronavirus (BCoV) persistence which leads to
translation attenuation of the downstream ORF. Here, we report the unexpected
identification of leaderless genomes, in addition to leader-containing genomes,
in a cell culture persistently infected with BCoV. The discovery was made by
using a head-to-tail ligation method that examines genomic 5'-terminal sequences
at different times postinfection. Functional analyses of the leaderless genomic
RNA in a BCoV defective interfering (DI) RNA revealed that (1) the leaderless
genome was able to serve as a template for the synthesis of negative-strand
genome, although it cannot perform replicative positive-strand genomic RNA
synthesis, and (2) the leaderless genome retained its function in translation and
transcription, although the efficiency of these processes was impaired.
Therefore, this previously unidentified leaderless genome is associated with the
attenuation of genome expression. Whether the leaderless genome contributes to
the establishment of persistent infection remains to be determined.
PMID- 24349215
TI - The PS1 hairpin of Mcm3 is essential for viability and for DNA unwinding in
vitro.
AB - The pre-sensor 1 (PS1) hairpin is found in ring-shaped helicases of the AAA+
family (ATPases associated with a variety of cellular activities) of proteins and
is implicated in DNA translocation during DNA unwinding of archaeal mini
chromosome maintenance (MCM) and superfamily 3 viral replicative helicases. To
determine whether the PS1 hairpin is required for the function of the eukaryotic
replicative helicase, Mcm2-7 (also comprised of AAA+ proteins), we mutated the
conserved lysine residue in the putative PS1 hairpin motif in each of the
Saccharomyces cerevisiae Mcm2-7 subunits to alanine. Interestingly, only the PS1
hairpin of Mcm3 was essential for viability. While mutation of the PS1 hairpin in
the remaining MCM subunits resulted in minimal phenotypes, with the exception of
Mcm7 which showed slow growth under all conditions examined, the viable alleles
were synthetic lethal with each other. Reconstituted Mcm2-7 containing Mcm3 with
the PS1 mutation (Mcm3(K499A)) had severely decreased helicase activity. The lack
of helicase activity provides a probable explanation for the inviability of the
mcm3(K499A) strain. The ATPase activity of Mcm2-7(3K499A) was similar to the wild
type complex, but its interaction with single-stranded DNA in an electrophoretic
mobility shift assay and its associations in cells were subtly altered. Together,
these findings indicate that the PS1 hairpins in the Mcm2-7 subunits have
important and distinct functions, most evident by the essential nature of the
Mcm3 PS1 hairpin in DNA unwinding.
PMID- 24349216
TI - Syndromic surveillance using veterinary laboratory data: algorithm combination
and customization of alerts.
AB - BACKGROUND: Syndromic surveillance research has focused on two main themes: the
search for data sources that can provide early disease detection; and the
development of efficient algorithms that can detect potential outbreak signals.
METHODS: This work combines three algorithms that have demonstrated solid
performance in detecting simulated outbreak signals of varying shapes in time
series of laboratory submissions counts. These are: the Shewhart control charts
designed to detect sudden spikes in counts; the EWMA control charts developed to
detect slow increasing outbreaks; and the Holt-Winters exponential smoothing,
which can explicitly account for temporal effects in the data stream monitored. A
scoring system to detect and report alarms using these algorithms in a
complementary way is proposed. RESULTS: The use of multiple algorithms in
parallel resulted in increased system sensitivity. Specificity was decreased in
simulated data, but the number of false alarms per year when the approach was
applied to real data was considered manageable (between 1 and 3 per year for each
of ten syndromic groups monitored). The automated implementation of this
approach, including a method for on-line filtering of potential outbreak signals
is described. CONCLUSION: The developed system provides high sensitivity for
detection of potential outbreak signals while also providing robustness and
flexibility in establishing what signals constitute an alarm. This flexibility
allows an analyst to customize the system for different syndromes.
PMID- 24349217
TI - Colonisation and diversification of the Zenaida Dove (Zenaida aurita) in the
Antilles: phylogeography, contemporary gene flow and morphological divergence.
AB - Caribbean avifaunal biogeography has been mainly studied based on mitochondrial
DNA. Here, we investigated both past and recent island differentiation and micro
evolutionary changes in the Zenaida Dove (Zenaida aurita) based on combined
information from one mitochondrial (Cytochrome c Oxydase subunit I, COI) and 13
microsatellite markers and four morphological characters. This Caribbean endemic
and abundant species has a large distribution, and two subspecies are supposed to
occur: Z. a. zenaida in the Greater Antilles (GA) and Z. a. aurita in the Lesser
Antilles (LA). Doves were sampled on two GA islands (Puerto Rico and the British
Virgin Islands) and six LA islands (Saint Barthelemy, Guadeloupe, Les Saintes,
Martinique, Saint Lucia and Barbados). Eleven COI haplotypes were observed that
could be assembled in two distinct lineages, with six specific to GA, four to LA,
the remaining one occurring in all islands. However, the level of divergence
between those two lineages was too moderate to fully corroborate the existence of
two subspecies. Colonisation of the studied islands appeared to be a recent
process. However, both phenotypic and microsatellite data suggest that
differentiation is already under way between all of them, partly associated with
the existence of limited gene flow. No isolation by distance was observed.
Differentiation for morphological traits was more pronounced than for neutral
markers. These results suggest that despite recent colonisation, genetic drift
and/or restricted gene flow are promoting differentiation for neutral markers.
Variation in selective pressures between islands may explain the observed
phenotypic differentiation.
PMID- 24349218
TI - Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF
beta1.
AB - Transforming growth factor beta1 (TGF-beta1) is the pivotal pro-fibrogenic
cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-beta1
or blocking its signaling pathways is considered to be a promising therapeutic
strategy for hepatic fibrosis. In this study, we evaluated the feasibility of
attenuating hepatic fibrosis by vaccination against TGF-beta1 with TGF-beta1
kinoids. Two TGF-beta1 kinoid vaccines were prepared by cross-linking TGF-beta1
derived polypeptides (TGF-beta1(25)-[41-65] and TGF-beta1(30)-[83-112]) to
keyhole limpet hemocyanin (KLH). Immunization with the two TGF-beta1 kinoids
efficiently elicited the production of high-levels of TGF-beta1-specific
antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay
(ELISA) and Western blotting. The antisera neutralized TGF-beta1-induced growth
inhibition on mink lung epithelial cells (Mv1Lu) and attenuated TGF-beta1-induced
Smad2/3 phosphorylation, alpha-SMA, collagen type 1 alpha 2 (COL1A2), plasminogen
activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase-1 (TIMP
1) expression in the rat hepatic stellate cell (HSC) line, HSC-T6. Vaccination
against TGF-beta1 with the kinoids significantly suppressed CCl4-induced collagen
deposition and the expression of alpha-SMA and desmin, attenuated hepatocyte
apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results
demonstrated that immunization with the TGF-beta1 kinoids efficiently attenuated
CCl4-induced hepatic fibrosis and liver injury. Our study suggests that
vaccination against TGF-beta1 might be developed into a feasible therapeutic
approach for the treatment of chronic fibrotic liver diseases.
PMID- 24349219
TI - KIAA1462, a coronary artery disease associated gene, is a candidate gene for late
onset Alzheimer disease in APOE carriers.
AB - Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more
than five million Americans. In this study, we have used updated genetic linkage
data from chromosome 10 in combination with expression data from serial analysis
of gene expression to choose a new set of thirteen candidate genes for genetic
analysis in late onset Alzheimer disease (LOAD). Results in this study identify
the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes
exist at this locus, KIAA1462, a gene associated with coronary artery disease,
and "rokimi", encoding an untranslated spliced RNA The genetic architecture at
this locus suggests that the gene product important in this association is either
"rokimi", or a different isoform of KIAA1462 than the isoform that is important
in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is
a more attractive candidate for association with LOAD in APOE4 carriers than
"rokimi" which had no detectable expression in brain.
PMID- 24349220
TI - Human CD8+ T cells from TB pleurisy respond to four immunodominant epitopes in
Mtb CFP10 restricted by HLA-B alleles.
AB - CD8(+) T cells are essential for host defense to Mycobacterium tuberculosis (Mtb)
infection and identification of CD8(+) T cell epitopes from Mtb is of importance
for the development of effective peptide-based diagnostics and vaccines. We
previously demonstrated that the secreted 10-KDa culture filtrate protein (CFP10)
from Mtb is a potent CD8(+) T cell antigen but the repertoire and dominance
pattern of human CD8 epitopes for CFP10 remained poorly characterized. In the
present study, we undertook to define immunodominant CD8 epitopes involved in
CFP10 using a panel of CFP10-derived 13-15 amino acid (aa) peptides overlapping
by 11 aa. Four peptides in CFP10 were observed to induce significant CD8(+) T
cell responses and we further determined the size of the epitopes involved in
each individual peptide tested. Four 9 aa CD8 epitopes were finally identified
and deleting a single amino acid from the N or C terminus of either peptide
markedly reduced IFN-gamma production, suggesting that they are minimum of CD8
epitopes. In the individuals tested, each epitope represented a single
immunodominant response in CD8(+) T cells. The epitope-specific CD8(+) T cells
displayed effector or effector memory phenotypes and could upregulate the
expression of CD107a/b upon antigen stimulation. In addition, we found that
epitope-specific CD8(+) T cells shared biased usage of T cell receptor (TCR)
variable region of beta chain (Vbeta) 12, 9, 7.2 or Vbeta4 chains. As judged from
HLA-typing results and using bioinformatics technology for prediction of MHC
binding affinity, we found that the epitope-specific CD8(+) T cells are all
restricted by HLA-B alleles. Our findings suggest that the four epitopes in CFP10
recognized by CD8(+) T cells might be of importance for the development of Mtb
peptide-based vaccines and for improved diagnosis of TB in humans.
PMID- 24349221
TI - Phylogenetic evidence of long distance dispersal and transmission of piscine
reovirus (PRV) between farmed and wild Atlantic salmon.
AB - The extent and effect of disease interaction and pathogen exchange between wild
and farmed fish populations is an ongoing debate and an area of research that is
difficult to explore. The objective of this study was to investigate pathogen
transmission between farmed and wild Atlantic salmon (Salmo salar L.) populations
in Norway by means of molecular epidemiology. Piscine reovirus (PRV) was selected
as the model organism as it is widely distributed in both farmed and wild
Atlantic salmon in Norway, and because infection not necessarily will lead to
mortality through development of disease. A matrix comprised of PRV protein
coding sequences S1, S2 and S4 from wild, hatchery-reared and farmed Atlantic
salmon in addition to one sea-trout (Salmo trutta L.) was examined. Phylogenetic
analyses based on maximum likelihood and Bayesian inference indicate long
distance transport of PRV and exchange of virus between populations. The results
are discussed in the context of Atlantic salmon ecology and the structure of the
Norwegian salmon industry. We conclude that the lack of a geographical pattern in
the phylogenetic trees is caused by extensive exchange of PRV. In addition, the
detailed topography of the trees indicates long distance transportation of PRV.
Through its size, structure and infection status, the Atlantic salmon farming
industry has the capacity to play a central role in both long distance
transportation and transmission of pathogens. Despite extensive migration, wild
salmon probably play a minor role as they are fewer in numbers, appear at lower
densities and are less likely to be infected. An open question is the
relationship between the PRV sequences found in marine fish and those originating
from salmon.
PMID- 24349222
TI - Soluble tumor necrosis factor related apoptosis inducing ligand level as a
predictor of severity of sepsis and the risk of mortality in septic patients.
AB - BACKGROUND: Tumor necrosis factor related apoptosis inducing ligand (TRAIL) as a
member of the TNF gene superfamily induces apoptosis primarily in tumor cells.
TRAIL also plays an important role in the modulation of inflammatory responses,
especially in the process of immune paralysis. The aim of the present study was
to examine soluble TRAIL (sTRAIL) levels in septic patients in an attempt to
explore the association between sTRAIL level and the risk of mortality. METHODS:
Plasma sTRAIL levels were detected by ELISA in 50 septic patients and 20 healthy
volunteers. HLA-DR expression in monocytes was detected by flow cytometry.
Selective biochemical parameters were recorded, and patients were monitored in a
28-day period for mortality. RESULTS: The mean plasma sTRAIL level in septic
patients was significantly lower than that in healthy controls (16.9+/-8.3 vs.
68.3+/-8.6 pg/ml, P<0.01), and was significantly higher in 28-day survivors than
those in non-survivors (19.4+/-9.8 vs. 13.9+/-4.7 pg/ml, P<0.05). Univariate
analysis indicated that plasma sTRAIL level was positively correlated with
monocyte and lymphocyte counts and HLA-DR expression level (r = 0.5, P<0.01; r =
0.3, P<0.05; r = 0.43, P<0.01, respectively). STRAIL level was negatively
correlated with APACHE II score, BUN and age (r = -0.48, P<0.01; r = -0.29,
P<0.05; r = -0.45, P<0.01, respectively). Multiple linear regression analysis
indicated that the predictor of plasma soluble TRAIL level was HLA-DR expression
(P<0.01). CONCLUSION: Low plasma sTRAIL levels were associated with immune
paralysis and a high risk of mortality in patients with septic shock. sTRAIL may
prove to be a potential biomarker of immune function and predict the survival of
septic patients.
PMID- 24349223
TI - Carbon storages in plantation ecosystems in sand source areas of north Beijing,
China.
AB - Afforestation is a mitigation option to reduce the increased atmospheric carbon
dioxide levels as well as the predicted high possibility of climate change. In
this paper, vegetation survey data, statistical database, National Forest
Resource Inventory database, and allometric equations were used to estimate
carbon density (carbon mass per hectare) and carbon storage, and identify the
size and spatial distribution of forest carbon sinks in plantation ecosystems in
sand source areas of north Beijing, China. From 2001 to the end of 2010, the
forest areas increased more than 2.3 million ha, and total carbon storage in
forest ecosystems was 173.02 Tg C, of which 82.80 percent was contained in soil
in the top 0-100 cm layer. Younger forests have a large potential for enhancing
carbon sequestration in terrestrial ecosystems than older ones. Regarding future
afforestation efforts, it will be more effective to increase forest area and
vegetation carbon density through selection of appropriate tree species and stand
structure according to local climate and soil conditions, and application of
proper forest management including land-shaping, artificial tending and fencing
plantations. It would be also important to protect the organic carbon in surface
soils during forest management.
PMID- 24349224
TI - Evaluation of elevated mean pulmonary arterial pressure based on magnetic
resonance 4D velocity mapping: comparison of visualization techniques.
AB - PURPOSE: Three-dimensional (3D) magnetic resonance phase contrast imaging (PC
MRI) allows non-invasive diagnosis of pulmonary hypertension (PH) and estimation
of elevated mean pulmonary arterial pressure (mPAP) based on vortical motion of
blood in the main pulmonary artery. The purpose of the present study was to
compare the presence and duration of PH-associated vortices derived from
different flow visualization techniques with special respect to their performance
for non-invasive assessment of elevated mPAP and diagnosis of PH. METHODS: Fifty
patients with suspected PH (23 patients with and 27 without PH) were investigated
by right heart catheterization and time-resolved PC-MRI of the main pulmonary
artery. PC-MRI data were visualized with dedicated prototype software, providing
3D vector, multi-planar reformatted (MPR) 2D vector, streamline, and particle
trace representation of flow patterns. Persistence of PH-associated vortical
blood flow (tvortex) was evaluated with all visualization techniques.
Dependencies of tvortex on visualization techniques were analyzed by means of
correlation and receiver operating characteristic (ROC) curve analysis. RESULTS:
tvortex values from 3D vector visualization correlated strongly with those from
other visualization techniques (r = 0.98, 0.98 and 0.97 for MPR, streamline and
particle trace visualization, respectively). Areas under ROC curves for diagnosis
of PH based on tvortex did not differ significantly and were 0.998 for 3D vector,
MPR vector and particle trace visualization and 0.999 for streamline
visualization. Correlations between elevated mPAP and tvortex in patients with PH
were r = 0.96, 0.93, 0.95 and 0.92 for 3D vector, MPR vector, streamline and
particle trace visualization, respectively. Corresponding standard deviations
from the linear regression lines ranged between 3 and 4 mmHg. CONCLUSION: 3D
vector, MPR vector, streamline as well as particle trace visualization of time
resolved 3D PC-MRI data of the main pulmonary artery can be employed for accurate
vortex-based diagnosis of PH and estimation of elevated mPAP.
PMID- 24349225
TI - Safety, immunogenicity and duration of immunity elicited by an inactivated bovine
ephemeral fever vaccine.
AB - Bovine ephemeral fever (BEF) is an economically important viral vector-borne
cattle disease. Several live-attenuated, inactivated and recombinant vaccines
have been tested, demonstrating varying efficacy. However, to the best of our
knowledge, duration of immunity conferred by an inactivated vaccine has never
been reported. In the last decade, Israel has faced an increasing number of BEF
outbreaks. The need for an effective vaccine compatible with strains circulating
in the Middle East region led to the development of a MONTANIDETM ISA 206 VG
(water-in-oil-in-water), inactivated vaccine based on a local strain. We tested
the safety, immunogenicity and duration of immunity conferred by this vaccine.
The induced neutralizing antibody (NA) response was followed for 493 days in 40
cows vaccinated by different protocols. The vaccine did not cause adverse
reactions or a decrease in milk production. All cows [except 2 (6.7%) which did
not respond to vaccination] showed a significant rise in NA titer of up to 1:256
following the second, third or fourth booster vaccination. Neutralizing antibody
levels declined gradually to 1:16 up to 120 days post vaccination. This decline
continued in cows vaccinated only twice, whereas cows vaccinated 3 or 4 times
showed stable titers of approximately 1:16 for up to 267 days post vaccination.
At least three vaccinations with the inactivated BEF vaccine were needed to
confer long-lasting immunity. These results may have significant implications for
the choice of vaccination protocol with inactivated BEF vaccines. Complementary
challenge data should however be added to the above results in order to determine
what is the minimal NA response conferring protection from clinical disease.
PMID- 24349227
TI - The wallpaper effect: the contact hypothesis fails for minority group members who
live in areas with a high proportion of majority group members.
AB - We aim to provide one explanation for why the link between contact and prejudice
is consistently less strong for minority group members than it is for majority
group members. Specifically, we propose a "wallpaper effect" such that contact
works to increase minority group members' positivity towards majority groups when
they live in areas densely populated with other minority group members.
Conversely, we suggest that when minority group members live in neighborhoods
patterned with majority group faces (as is so often the case), contact will be
less transformative. We test this assumption using a large sample of both New
Zealander minority (Maori; N = 925) and majority (European; N = 3805) group
members. In line with predictions, Maori who lived in minority dense
neighborhoods showed the traditional association between contact and increased
warmth towards New Zealander Europeans. This relationship, however, was weak or
non-existent when they lived in primarily European neighborhoods. Contact effects
in majority group members were unaffected by neighborhood composition. The
interaction held when controlling for, and was not explained by: gender, income,
experiences of harm, cognitions of race-based rejection, or realistic threat. We
provide the first evidence to suggest that when it comes to minority group
members' intergroup attitudes, contact with majority group members may be a
relatively ineffective predictor unless the "wallpaper" of their lives is
minority-dense.
PMID- 24349226
TI - Sequential effects in judgements of attractiveness: the influences of face race
and sex.
AB - In perceptual decision-making, a person's response on a given trial is influenced
by their response on the immediately preceding trial. This sequential effect was
initially demonstrated in psychophysical tasks, but has now been found in more
complex, real-world judgements. The similarity of the current and previous
stimuli determines the nature of the effect, with more similar items producing
assimilation in judgements, while less similarity can cause a contrast effect.
Previous research found assimilation in ratings of facial attractiveness, and
here, we investigated whether this effect is influenced by the social categories
of the faces presented. Over three experiments, participants rated the
attractiveness of own- (White) and other-race (Chinese) faces of both sexes that
appeared successively. Through blocking trials by race (Experiment 1), sex
(Experiment 2), or both dimensions (Experiment 3), we could examine how
sequential judgements were altered by the salience of different social categories
in face sequences. For sequences that varied in sex alone, own-race faces showed
significantly less opposite-sex assimilation (male and female faces perceived as
dissimilar), while other-race faces showed equal assimilation for opposite- and
same-sex sequences (male and female faces were not differentiated). For sequences
that varied in race alone, categorisation by race resulted in no opposite-race
assimilation for either sex of face (White and Chinese faces perceived as
dissimilar). For sequences that varied in both race and sex, same-category
assimilation was significantly greater than opposite-category. Our results
suggest that the race of a face represents a superordinate category relative to
sex. These findings demonstrate the importance of social categories when
considering sequential judgements of faces, and also highlight a novel approach
for investigating how multiple social dimensions interact during decision-making.
PMID- 24349228
TI - Predation limits spread of Didemnum vexillum into natural habitats from refuges
on anthropogenic structures.
AB - Non-indigenous species can dominate fouling assemblages on artificial structures
in marine environments; however, the extent to which infected structures act as
reservoirs for subsequent spread to natural habitats is poorly understood.
Didemnum vexillum is one of few colonial ascidian species that is widely reported
to be highly invasive in natural ecosystems, but which in New Zealand
proliferates only on suspended structures. Experimental work revealed that D.
vexillum established equally well on suspended artificial and natural substrata,
and was able to overgrow suspended settlement plates that were completely covered
in other cosmopolitan fouling species. Fragmentation led to a level of D.
vexillum cover that was significantly greater than was achieved as a result of
ambient larval recruitment. The species failed to establish following fragment
transplants onto seabed cobbles and into beds of macroalgae. The establishment
success of D. vexillum was greatest in summer compared with autumn, and on the
underside of experimental settlement plates that were suspended off the seabed to
avoid benthic predators. Where benthic predation pressure was reduced by caging,
D. vexillum establishment success was broadly comparable to suspended treatments;
by contrast, the species did not establish on the face-up aspect of uncaged
plates. This study provides compelling evidence that benthic predation was a key
mechanism that prevented D. vexillum's establishment in the cobble habitats of
the study region. The widespread occurrence of D. vexillum on suspended
anthropogenic structures is consistent with evidence for other sessile
invertebrates that such habitats provide a refuge from benthic predation. For
invasive species generally, anthropogenic structures are likely to be most
important as propagule reservoirs for spread to natural habitats in situations
where predation and other mechanisms do not limit their subsequent proliferation.
PMID- 24349229
TI - Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small
cell lung cancer.
AB - The targeting of oncogenic 'driver' kinases with small molecule inhibitors has
proven to be a highly effective therapeutic strategy in selected non-small cell
lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies
invariably arises and is a major limitation to patient care. ROS1 fusion proteins
are a recently described class of oncogenic driver, and NSCLC patients that
express these fusions generally respond well to ROS1-targeted therapy. In this
study, we sought to determine mechanisms of acquired resistance to ROS1
inhibition. To accomplish this, we analyzed tumor samples from a patient who
initially responded to the ROS1 inhibitor crizotinib but eventually developed
acquired resistance. In addition, we generated a ROS1 inhibition-resistant
derivative of the initially sensitive NSCLC cell line HCC78. Previously described
mechanisms of acquired resistance to tyrosine kinase inhibitors including target
kinase-domain mutation, target copy number gain, epithelial-mesenchymal
transition, and conversion to small cell lung cancer histology were found to not
underlie resistance in the patient sample or resistant cell line. However, we did
observe a switch in the control of growth and survival signaling pathways from
ROS1 to EGFR in the resistant cell line. As a result of this switch, ROS1
inhibition-resistant HCC78 cells became sensitive to EGFR inhibition, an effect
that was enhanced by co-treatment with a ROS1 inhibitor. Our results suggest that
co-inhibition of ROS1 and EGFR may be an effective strategy to combat resistance
to targeted therapy in some ROS1 fusion-positive NSCLC patients.
PMID- 24349230
TI - TFpredict and SABINE: sequence-based prediction of structural and functional
characteristics of transcription factors.
AB - One of the key mechanisms of transcriptional control are the specific connections
between transcription factors (TF) and cis-regulatory elements in gene promoters.
The elucidation of these specific protein-DNA interactions is crucial to gain
insights into the complex regulatory mechanisms and networks underlying the
adaptation of organisms to dynamically changing environmental conditions. As
experimental techniques for determining TF binding sites are expensive and mostly
performed for selected TFs only, accurate computational approaches are needed to
analyze transcriptional regulation in eukaryotes on a genome-wide level. We
implemented a four-step classification workflow which for a given protein
sequence (1) discriminates TFs from other proteins, (2) determines the structural
superclass of TFs, (3) identifies the DNA-binding domains of TFs and (4) predicts
their cis-acting DNA motif. While existing tools were extended and adapted for
performing the latter two prediction steps, the first two steps are based on a
novel numeric sequence representation which allows for combining existing
knowledge from a BLAST scan with robust machine learning-based classification. By
evaluation on a set of experimentally confirmed TFs and non-TFs, we demonstrate
that our new protein sequence representation facilitates more reliable
identification and structural classification of TFs than previously proposed
sequence-derived features. The algorithms underlying our proposed methodology are
implemented in the two complementary tools TFpredict and SABINE. The online and
stand-alone versions of TFpredict and SABINE are freely available to academics at
http://www.cogsys.cs.uni-tuebingen.de/software/TFpredict/ and
http://www.cogsys.cs.uni-tuebingen.de/software/SABINE/.
PMID- 24349232
TI - Bottom-water conditions in a marine basin after the Cretaceous-Paleogene impact
event: timing the recovery of oxygen levels and productivity.
AB - An ultra-high-resolution analysis of major and trace element contents from the
Cretaceous-Paleogene boundary interval in the Caravaca section, southeast Spain,
reveals a quick recovery of depositional conditions after the impact event.
Enrichment/depletion profiles of redox sensitive elements indicate significant
geochemical anomalies just within the boundary ejecta layer, supporting an
instantaneous recovery--some 10(2) years--of pre-impact conditions in terms of
oxygenation. Geochemical redox proxies point to oxygen levels comparable to those
at the end of the Cretaceous shortly after impact, which is further evidenced by
the contemporary macrobenthic colonization of opportunistic tracemakers. Recovery
of the oxygen conditions was therefore several orders shorter than traditional
proposals (10(4)-10(5) years), suggesting a probable rapid recovery of deep-sea
ecosystems at bottom and in intermediate waters.
PMID- 24349231
TI - Human host defense peptide LL-37 stimulates virulence factor production and
adaptive resistance in Pseudomonas aeruginosa.
AB - A multitude of different virulence factors as well as the ability to rapidly
adapt to adverse environmental conditions are important features for the high
pathogenicity of Pseudomonas aeruginosa. Both virulence and adaptive resistance
are tightly controlled by a complex regulatory network and respond to external
stimuli, such as host signals or antibiotic stress, in a highly specific manner.
Here, we demonstrate that physiological concentrations of the human host defense
peptide LL-37 promote virulence factor production as well as an adaptive
resistance against fluoroquinolone and aminoglycoside antibiotics in P.
aeruginosa PAO1. Microarray analyses of P. aeruginosa cells exposed to LL-37
revealed an upregulation of gene clusters involved in the production of quorum
sensing molecules and secreted virulence factors (PQS, phenazine, hydrogen
cyanide (HCN), elastase and rhamnolipids) and in lipopolysaccharide (LPS)
modification as well as an induction of genes encoding multidrug efflux pumps
MexCD-OprJ and MexGHI-OpmD. Accordingly, we detected significantly elevated
levels of toxic metabolites and proteases in bacterial supernatants after LL-37
treatment. Pre-incubation of bacteria with LL-37 for 2 h led to a decreased
susceptibility towards gentamicin and ciprofloxacin. Quantitative Realtime PCR
results using a PAO1-pqsE mutant strain present evidence that the quinolone
response protein and virulence regulator PqsE may be implicated in the regulation
of the observed phenotype in response to LL-37. Further experiments with
synthetic cationic antimicrobial peptides IDR-1018, 1037 and HHC-36 showed no
induction of pqsE expression, suggesting a new role of PqsE as highly specific
host stress sensor.
PMID- 24349233
TI - Localization of microfibrillar-associated protein 4 (MFAP4) in human tissues:
clinical evaluation of serum MFAP4 and its association with various
cardiovascular conditions.
AB - Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular
matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and
MFAP4 protein expression. Moreover, we aimed to evaluate the significance of
MFAP4 as a marker of cardiovascular disease (CVD) and to correlate MFAP4 with
other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and
osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was
more highly expressed in the heart, lung, and intestine than in other elastic
tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein
mainly at sites rich in elastic fibers and within blood vessels in all tissues
investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in
a clinical cohort of 172 patients consisting of 5 matched groups with varying
degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI), 2:
patients with non-STEMI, 3: patients destined for vascular surgery because of
various atherosclerotic diseases (stable atherosclerotic disease), 4: apparently
healthy individuals with documented coronary artery calcification (CAC-positive),
and 5: apparently healthy individuals without signs of coronary artery
calcification (CAC-negative). Serum MFAP4 levels were significantly lower in
patients with stable atherosclerotic disease than CAC-negative individuals
(p<0.05). Furthermore, lower serum MFAP4 levels were present in patients with
stable atherosclerotic disease compared with STEMI and non-STEMI patients
(p<0.05). In patients with stable atherosclerotic disease, positive correlations
between MFAP4 and both fibulin-1 (rho = 0.50; p = 0.0244) and OPG (rho = 0.62; p
= 0.0014) were found. Together, these results indicate that MFAP4 is mainly
located in elastic fibers and is highly expressed in blood vessels. The present
study suggests that serum MFAP4 varies in groups of patients with different
cardiovascular conditions. Further studies are warranted to describe the role of
serum MFAP4 as a biomarker of stable atherosclerotic disease.
PMID- 24349234
TI - Surgically induced interpregnancy weight loss and prevalence of overweight and
obesity in offspring.
AB - INTRODUCTION: According to the fetal overnutrition hypothesis, obesity in
pregnancy predisposes the offspring to obesity. Previous studies have suggested
that after biliopancreatic surgery for obesity, the offspring is less likely to
be obese. This study aims to further compare the BMI development of children born
before and after maternal surgical weight loss. METHOD: Women with at least one
child born before and one child born after bariatric surgery were identified by
record-linkage. Information about maternal BMI was extracted from medical
records, as was information about the children's BMI from birth to 10 years of
age. We retrieved BMI data at four years of age for 340 children, born to 223
women (164 children born before surgery (BS), 176 children born after surgery
(AS)). We evaluated prevalence of overweight/obesity and mean BMI in children
born BS and AS at the ages of four, six and ten using GEE regression models. For
71 families, where we had complete data on mother and both children, we used a
fixed-effects regression model to explore the association between differences in
maternal BMI in w10 of the pre- and post-operative pregnancies with siblings' BMI
differences at age four. RESULTS: In no age group did we see a significantly
reduced prevalence of overweight/obesity AS. For 10-year-old girls, the AS group
had significantly higher rates of obesity. There was no association between
differences in maternal BMI in early pregnancy and differences in siblings' BMI
at four years of age (beta = -0.01, CI 95% = -0.11; 0.09). CONCLUSIONS: We have
been unable to demonstrate any effect of bariatric surgery on weight development
in offspring. It seems unlikely that restrictive bariatric surgery conveys a
protective effect in offspring with regards to obesity.
PMID- 24349235
TI - Prophage-mediated dynamics of 'Candidatus Liberibacter asiaticus' populations,
the destructive bacterial pathogens of citrus huanglongbing.
AB - Prophages are highly dynamic components in the bacterial genome and play an
important role in intraspecies variations. There are at least two prophages in
the chromosomes of Candidatus Liberibacter asiaticus' (Las) Floridian isolates.
Las is both unculturable and the most prevalent species of Liberibacter pathogens
that cause huanglongbing (HLB), a worldwide destructive disease of citrus. In
this study, seven new prophage variants resulting from two hyper-variable regions
were identified by screening clone libraries of infected citrus, periwinkle and
psyllids. Among them, Types A and B share highly conserved sequences and localize
within the two prophages, FP1 and FP2, respectively. Although Types B and C were
abundant in all three libraries, Type A was much more abundant in the libraries
from the Las-infected psyllids than from the Las-infected plants, and Type D was
only identified in libraries from the infected host plants but not from the
infected psyllids. Sequence analysis of these variants revealed that the
variations may result from recombination and rearrangement events. Conventional
PCR results using type-specific molecular markers indicated that A, B, C and D
are the four most abundant types in Las-infected citrus and periwinkle. However,
only three types, A, B and C are abundant in Las-infected psyllids. Typing
results for Las-infected citrus field samples indicated that mixed populations of
Las bacteria present in Floridian isolates, but only the Type D population was
correlated with the blotchy mottle symptom. Extended cloning and sequencing of
the Type D region revealed a third prophage/phage in the Las genome, which may
derive from the recombination of FP1 and FP2. Dramatic variations in these
prophage regions were also found among the global Las isolates. These results are
the first to demonstrate the prophage/phage-mediated dynamics of Las populations
in plant and insect hosts, and their correlation with insect transmission and
disease development.
PMID- 24349236
TI - Factors associated with failed treatment: an analysis of 121,744 women embarking
on their first IVF cycles.
AB - BACKGROUND: In-vitro fertilization (IVF) is the treatment of choice for
unresolved infertility. It comprises a number of key steps, each of which has to
be negotiated before the next is attempted, but the factors which are associated
with failure at each stage have not been reported. METHODS AND FINDINGS: We
analyzed anonymised national data on women undergoing their first fresh
autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United
Kingdom between 2000 and 2007 to predict factors associated with overall lack of
livebirth as well as the chance of non-progress at different stages of an IVF
cycle. A total of 121,744 women were included in this analysis. Multivariable
models underlined the importance of increased female age and duration of
infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor
infertility in predicting the risk of not having a live birth in an IVF
treatment. At each stage, a woman's chance of proceeding to the next stage of IVF
treatment is affected by increased age and duration of infertility. The intention
to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased
risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92,
0.94) but this association is reversed at a later stage once fertilisation has
been confirmed (RR=1.01, 99%CI 1.00, 1.03). CONCLUSIONS: Female age is a key
predictor of failure to have a livebirth following IVF as well as the risk of
poor performance at each stage of treatment. While increased duration of
infertility is also associated with worse outcomes at every stage, its impact
appears to be less influential. Women embarking on ICSI treatment for male factor
infertility have a lower chance of treatment failure but this does not appear to
be due to increased chances of implantation of ICSI embryos.
PMID- 24349237
TI - Procalcitonin levels predict acute kidney injury and prognosis in acute
pancreatitis: a prospective study.
AB - BACKGROUND: Acute kidney injury (AKI) has been proposed as a leading cause of
mortality for acute pancreatitis (AP) patients admitted to the intensive care
unit (ICU). This study investigated the predictive value of procalcitonin (PCT)
for AKI development and relevant prognosis in patients with AP, and compared
PCT's predictive power with that of other inflammation-related variables.
METHODS: Between January 2011 and March 2013, we enrolled 305 cases with acute
pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA),
interleukin-6 (IL-6), and C reactive protein (CRP) were determined on admission.
Serum PCT was tested in patients who developed AKI on the day of AKI occurrence
and on either day 28 after occurrence (for survivors) or on the day of death (for
those who died within 28 days). RESULTS: Serum PCT levels were 100-fold higher in
the AKI group than in the non-AKI group on the day of ICU admission (p<0.05). The
area under the receiver-operating characteristic (ROC) curve of PCT for
predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05). ROC
analysis revealed all variables tested had lower predictive performance for AKI
prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99) ng/ml) was
significantly (p<0.0001) lower than on the day of AKI occurrence (43.71
(19.24,65.69) ng/ml) in survivors, but the serum PCT level on death (63.73
(34.22,94.30) ng/ml) was higher than on the day of AKI occurrence (37.55
(18.70,74.12) ng/ml) in non-survivors, although there was no significant
difference between the two days in the latter group (p = 0.1365). CONCLUSION:
Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI
in patients with AP, and also can be used for dynamic evaluation of AKI
prognosis.
PMID- 24349238
TI - Local experience with extracorporeal membrane oxygenation in children with acute
fulminant myocarditis.
AB - To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in
children with acute fulminant myocarditis, we retrospectively analyzed the data
of five children with acute fulminant myocarditis in the intensive care unit
(ICU) at the Affiliated Children's Hospital, Zhejiang University from February
2009 to November 2012. The study group included two boys and three girls ranging
in age from 9 to 13 years (median 10 years). Body weight ranged from 25 to 33 kg
(mean 29.6 kg). They underwent extracorporeal membrane oxygenation (ECMO) through
a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40
142 h). Extracorporeal circulation was established in all five children. After
treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were
greatly improved in the four children who survived. These four children were
successfully weaned from ECMO and discharged from hospital machine-free, for a
survival rate of 80% (4/5). One child died still dependent on the machine. Cause
of death was irrecoverable cardiac function and multiple organ failure.
Complications during ECMO included three cases of suture bleeding, one case of
acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia.
During the follow-up period of 4-50 months, the four surviving children recovered
with normal cardiac function and no abnormal functions of other organs. The
application of ECMO in acute fulminant myocarditis, even in local centers that
experience low incidence of this disease, remains an effective approach. Larger
studies to determine optimal timing of placement on ECMO to guide local centers
are warranted.
PMID- 24349239
TI - Electrically conductive bulk composites through a contact-connected aggregate.
AB - This paper introduces a concept that allows the creation of low-resistance
composites using a network of compliant conductive aggregate units, connected
through contact, embedded within the composite. Due to the straight-forward
fabrication method of the aggregate, conductive composites can be created in
nearly arbitrary shapes and sizes, with a lower bound near the length scale of
the conductive cell used in the aggregate. The described instantiation involves
aggregate cells that are approximately spherical copper coils-of-coils within a
polymeric matrix, but the concept can be implemented with a wide range of
conductor elements, cell geometries, and matrix materials due to its lack of
reliance on specific material chemistries. The aggregate cell network provides a
conductive pathway that can have orders of magnitude lower resistance than that
of the matrix material--from 10(12) ohm-cm (approx.) for pure silicone rubber to
as low as 1 ohm-cm for the silicone/copper composite at room temperature for the
presented example. After describing the basic concept and key factors involved in
its success, three methods of implementing the aggregate into a matrix are then
addressed--unjammed packing, jammed packing, and pre-stressed jammed packing-
with an analysis of the tradeoffs between increased stiffness and improved
resistivity.
PMID- 24349240
TI - Overexpression of small heat shock protein LimHSP16.45 in Arabidopsis enhances
tolerance to abiotic stresses.
AB - Small heat shock proteins (smHSPs) play important and extensive roles in plant
defenses against abiotic stresses. We cloned a gene for a smHSP from the David
Lily (Lilium davidii (E. H. Wilson) Raffill var. Willmottiae), which we named
LimHSP16.45 based on its protein molecular weight. Its expression was induced by
many kinds of abiotic stresses in both the lily and transgenic plants of
Arabidopsis. Heterologous expression enhanced cell viability of the latter under
high temperatures, high salt, and oxidative stress, and heat shock granules
(HSGs) formed under heat or salinity treatment. Assays of enzymes showed that
LimHSP16.45 overexpression was related to greater activity by superoxide
dismutase and catalase in transgenic lines. Therefore, we conclude that
heterologous expression can protect plants against abiotic stresses by preventing
irreversible protein aggregation, and by scavenging cellular reactive oxygen
species.
PMID- 24349241
TI - A flexible approach for assessing functional landscape connectivity, with
application to greater sage-grouse (Centrocercus urophasianus).
AB - Connectivity of animal populations is an increasingly prominent concern in
fragmented landscapes, yet existing methodological and conceptual approaches
implicitly assume the presence of, or need for, discrete corridors. We tested
this assumption by developing a flexible conceptual approach that does not
assume, but allows for, the presence of discrete movement corridors. We
quantified functional connectivity habitat for greater sage-grouse (Centrocercus
urophasianus) across a large landscape in central western North America. We
assigned sample locations to a movement state (encamped, traveling and
relocating), and used Global Positioning System (GPS) location data and
conditional logistic regression to estimate state-specific resource selection
functions. Patterns of resource selection during different movement states
reflected selection for sagebrush and general avoidance of rough topography and
anthropogenic features. Distinct connectivity corridors were not common in the
5,625 km(2) study area. Rather, broad areas functioned as generally high or low
quality connectivity habitat. A comprehensive map predicting the quality of
connectivity habitat across the study area validated well based on a set of GPS
locations from independent greater sage-grouse. The functional relationship
between greater sage-grouse and the landscape did not always conform to the idea
of a discrete corridor. A more flexible consideration of landscape connectivity
may improve the efficacy of management actions by aligning those actions with the
spatial patterns by which animals interact with the landscape.
PMID- 24349242
TI - Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and
late-stage renal dysfunction via administration of fibroblast growth factor-21 is
associated with suppression of renal inflammation.
AB - BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney
disease, and is attributed to excessive lipid accumulation (hyperlipidemia).
Increasing evidence suggests that fibroblast growth factor (FGF)21 has a crucial
role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study
investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal
damage, and if so, the possible mechanism. METHODS: Mice were injected with free
fatty acids (FFAs, 10 mg/10 g body weight) or streptozotocin (150 mg/kg) to
establish a lipotoxic model or type 1 diabetic model, respectively.
Simultaneously the mice were treated with FGF21 (100 ug/kg) for 10 or 80 days.
The kidney weight-to-tibia length ratio and renal function were assessed.
Systematic and renal lipid levels were detected by ELISA and Oil Red O staining.
Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and
fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and
chronic diabetes were associated with lower kidney-to-tibia length ratio, higher
lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation,
oxidative stress and fibrosis also observed in the kidney of both mice models.
Deletion of the fgf21 gene further enhanced the above pathological changes, which
were significantly prevented by administration of exogenous FGF21. CONCLUSION:
These results suggest that FFA administration and diabetes induced renal damage,
which was further enhanced in FGF21 knock-out mice. Administration of FGF21
significantly prevented both FFA- and diabetes-induced renal damage partially by
decreasing renal lipid accumulation and suppressing inflammation, oxidative
stress, and fibrosis.
PMID- 24349243
TI - An allosteric regulator of R7-RGS proteins influences light-evoked activity and
glutamatergic waves in the inner retina.
AB - In the outer retina, G protein-coupled receptor (GPCR) signaling mediates
phototransduction and synaptic transmission between photoreceptors and ON bipolar
cells. In contrast, the functions of modulatory GPCR signaling networks in the
inner retina are less well understood. We addressed this question by determining
the consequences of augmenting modulatory Gi/o signaling driven by endogenous
transmitters. This was done by analyzing the effects of genetically ablating the
R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive
allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family
that deactivates Gi/oalpha subunits. We found that R7BP is expressed highly in
starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by
electroretinography and multielectrode array recordings of adult retina, ablation
of R7BP preserved outer retina function, but altered the firing rate and latency
of ON RGCs driven by rods and cones but not rods alone. In developing retina,
R7BP ablation increased the burst duration of glutamatergic waves whereas
cholinergic waves were unaffected. This effect on glutamatergic waves did not
result in impaired segregation of RGC projections to eye-specific domains of the
dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial
contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken
together these findings indicate that R7BP-dependent regulation of R7-RGS
proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs
in mature and developing retina.
PMID- 24349244
TI - Four-month-old infants' long-term memory for a stressful social event.
AB - Infants clearly show an early capacity for memory for inanimate emotionally
neutral events. However, their memory for social stress events has received far
less attention. The aim of the study was to investigate infants' memory for a
stressful social event (i.e., maternal unresponsiveness during the Still-Face
paradigm) after a 15-day recall interval using changes in behavioral responses
and salivary post-stress cortisol reactivity as measures of memory. Thirty-seven
infants were exposed to social stress two times (experimental condition); the
first time when they were 4 months of age and second exposure after a 2 week
interval. Infants in the control condition (N = 37) were exposed to social stress
just one time, at the age corresponding to the second exposure for infants in the
experimental condition (4 months plus 2 weeks). Given individual differences in
infants' reactivity to social stress events, we categorized infants as increasers
or decreasers based on their cortisol reactivity after their initial exposure to
the stress of the maternal still-face. Infants in the experimental condition,
both increasers and decreasers, showed a significant change in cortisol response
after the second exposure to the maternal still-face, though change was different
for each reactivity group. In contrast, age-matched infants with no prior
exposure to the maternal still-face showed similar post-stress cortisol
reactivity to the reactivity of the experimental infants at their first exposure.
There were no behavioral differences between increasers and decreasers during the
Still-Face paradigm and exposures to the social stress. Thus differences between
the experimental and control groups' post-stress cortisol reactivity was
associated with the experimental group having previous experience with the social
stress. These findings indicate long-term memory for social stress in infants as
young as 4 months of age.
PMID- 24349245
TI - High nasopharyngeal carriage of non-vaccine serotypes in Western Australian
aboriginal people following 10 years of pneumococcal conjugate vaccination.
AB - BACKGROUND: Invasive pneumococcal disease (IPD) continues to occur at high rates
among Australian Aboriginal people. The seven-valent pneumococcal conjugate
vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent
pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced
with 13vPCV in July 2011. Since carriage surveillance can supplement IPD
surveillance, we have monitored pneumococcal carriage in western Australia (WA)
since 2008 to assess the impact of the 10-year 7vPCV program. METHODS: We
collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied
regions of WA from August 2008 until June 2011. Specimens were cultured on
selective media. Pneumococcal isolates were serotyped by the quellung reaction.
RESULTS: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5
years of age, and 34.6%, 22.4% and 27.2% of people >=5 years. Of 43 pneumococcal
serotypes identified, the most common were 19A, 16F and 6C in children <5 years,
and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all
serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little
variation across all age groups. Serotypes 1 and 12F were rarely identified,
despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC
>=2ug/ml) was found in 1.6% of serotype 19A (5.2%), 19F (4.9%) and 16F (3.2%)
isolates and reduced penicillin susceptibility (MIC >=0.125ug/ml) in 24.9% of
isolates, particularly 19F (92.7%), 19A (41.3%), 16F (29.0%). Multi-resistance to
cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates.
Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed
complete resistance to penicillin. CONCLUSIONS: Ten years after introduction of
7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small
proportion of carried pneumococci. A large proportion of circulating serotypes
are not covered by any currently licensed vaccine.
PMID- 24349246
TI - The T309G MDM2 gene polymorphism is a novel risk factor for proliferative
vitreoretinopathy.
AB - Proliferative vitreoretinopathy (PVR) is still the major cause of failure in
retinal detachment (RD) surgery. It is believed that down-regulation in the p53
pathway could be an important key in PVR pathogenesis. The purpose was to
evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution
of T309G MDM2 genotypes among European subjects undergoing RD surgery was
evaluated. Proportions of genotypes between subsamples from different countries
were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and
rs1042522 in p53 gene was analyzed. Significant differences were observed
comparing MDM2 genotype frequencies at position 309 of intron 1 between cases
(GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%).
The proportions of genotypes between sub-samples from different countries showed
a significant difference. Distribution of GG genotype revealed differences in
Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands
(40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in
the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain
and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands
was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is
associated with a higher risk of developing PVR in patients undergoing a RD
surgery. Further studies are necessary to understand the role of this SNP in the
development of PVR.
PMID- 24349247
TI - Molecular mechanism of inhibition of the mitochondrial carnitine/acylcarnitine
transporter by omeprazole revealed by proteoliposome assay, mutagenesis and
bioinformatics.
AB - The effect of omeprazole on the mitochondrial carnitine/acylcarnitine transporter
has been studied in proteoliposomes. Externally added omeprazole inhibited the
carnitine/carnitine antiport catalysed by the transporter. The inhibition was
partially reversed by DTE indicating that it was caused by the covalent reaction
of omeprazole with Cys residue(s). Inhibition of the C-less mutant transporter
indicated also the occurrence of an alternative non-covalent mechanism. The IC50
of the inhibition of the WT and the C-less CACT by omeprazole were 5.4 uM and 29
uM, respectively. Inhibition kinetics showed non competitive inhibition of the WT
and competitive inhibition of the C-less. The presence of carnitine or
acylcarnitines during the incubation of the proteoliposomes with omeprazole
increased the inhibition. Using site-directed Cys mutants it was demonstrated
that C283 and C136 were essential for covalent inhibition. Molecular docking of
omeprazole with CACT indicated the formation of both covalent interactions with
C136 and C283 and non-covalent interactions in agreement with the experimental
data.
PMID- 24349248
TI - The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast
growth factor is probably mediated by the suppression of oxidative stress and
damage.
AB - BACKGROUND: Emerging evidence showed the beneficial effect of acidic fibroblast
growth factor (aFGF) on heart diseases. The present study investigated whether
non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the
underlying mechanisms, if any. METHODOLOGY/PRINCIPAL FINDINGS: Type 1 diabetes
was induced in mice by multiple intraperitoneal injections of low-dose
streptozotocin. Hyperglycemic and age-matched control mice were treated with or
without nm-aFGF at 10 ug/kg daily for 1 and 6 months. Blood pressure and cardiac
function were assessed. Cardiac H9c2 cell, human microvascular endothelial cells,
and rat cardiomyocytes were exposed to high glucose (25 mM) for mimicking an in
vitro diabetic condition for mechanistic studies. Oxidative stress, DNA damage,
cardiac hypertrophy and fibrosis were assessed by real-time qPCR,
immunofluorescent staining, Western blotting, and pathological examination. Nm
aFGF significantly prevented diabetes-induced hypertension and cardiac
dysfunction at 6 months. Mechanistic studies demonstrated that nm-aFGF showed the
similar preventive effect as the native aFGF on high glucose-induced oxidative
stress (increase generation of reactive oxygen species) and damage (cellular DNA
oxidation), cell hypertrophy, and fibrotic response (increased mRNA expression of
fibronectin) in three kinds of cells. These in vitro findings were recaptured by
examining the heart of the diabetic mice with and without nm-aFGF. CONCLUSIONS:
These results suggest that nm-aFGF can prevent diabetic cardiomyopathy, probably
through attenuation of cardiac oxidative stress, hypertrophy, and fibrosis.
PMID- 24349249
TI - Incidence, predictive factors, and clinical outcomes of acute kidney injury after
gastric surgery for gastric cancer.
AB - BACKGROUND: Postoperative acute kidney injury (AKI), a serious surgical
complication, is common after cardiac surgery; however, reports on AKI after
noncardiac surgery are limited. We sought to determine the incidence and
predictive factors of AKI after gastric surgery for gastric cancer and its
effects on the clinical outcomes. METHODS: We conducted a retrospective study of
4718 patients with normal renal function who underwent partial or total
gastrectomy for gastric cancer between June 2002 and December 2011. Postoperative
AKI was defined by serum creatinine change, as per the Kidney Disease Improving
Global Outcomes guideline. RESULTS: Of the 4718 patients, 679 (14.4%) developed
AKI. Length of hospital stay, intensive care unit admission rates, and in
hospital mortality rate (3.5% versus 0.2%) were significantly higher in patients
with AKI than in those without. AKI was also associated with requirement of renal
replacement therapy. Multivariate analysis revealed that male gender;
hypertension; chronic obstructive pulmonary disease; hypoalbuminemia (<4 g/dl);
use of diuretics, vasopressors, and contrast agents; and packed red blood cell
transfusion were independent predictors for AKI after gastric surgery.
Postoperative AKI and vasopressor use entailed a high risk of 3-month mortality
after multiple adjustments. CONCLUSIONS: AKI was common after gastric surgery for
gastric cancer and associated with adverse outcomes. We identified several
factors associated with postoperative AKI; recognition of these predictive
factors may help reduce the incidence of AKI after gastric surgery. Furthermore,
postoperative AKI in patients with gastric cancer is an important risk factor for
short-term mortality.
PMID- 24349250
TI - A change in configuration of the calmodulin-KCNQ channel complex underlies Ca2+
dependent modulation of KCNQ channel activity.
AB - All subtypes of KCNQ channel subunits (KCNQ1-5) require calmodulin as a co-factor
for functional channels. It has been demonstrated that calmodulin plays a
critical role in KCNQ channel trafficking as well as calcium-mediated current
modulation. However, how calcium-bound calmodulin suppresses the M-current is not
well understood. In this study, we investigated the molecular mechanism of KCNQ2
current suppression mediated by calcium-bound calmodulin. We show that calcium
induced slow calmodulin dissociation from the KCNQ2 channel subunit. In contrast,
in homomeric KCNQ3 channels, calcium facilitated calmodulin binding. We
demonstrate that this difference in calmodulin binding was due to the unique
cysteine residue in the KCNQ2 subunit at aa 527 in Helix B, which corresponds to
an arginine residue in other KCNQ subunits including KCNQ3. In addition, a KCNQ2
channel associated protein AKAP79/150 (79 for human, 150 for rodent orthologs)
also preferentially bound calcium-bound calmodulin. Therefore, the KCNQ2 channel
complex was able to retain calcium-bound calmodulin either through the AKPA79/150
or KCNQ3 subunit. Functionally, increasing intracellular calcium by ionomycin
suppressed currents generated by KCNQ2, KCNQ2(C527R) or heteromeric KCNQ2/KCNQ3
channels to an equivalent extent. This suggests that a change in the binding
configuration, rather than dissociation of calmodulin, is responsible for KCNQ
current suppression. Furthermore, we demonstrate that KCNQ current suppression
was accompanied by reduced KCNQ affinity toward phosphatidylinositol 4,5
bisphosphate (PIP2) when assessed by a voltage-sensitive phosphatase, Ci-VSP.
These results suggest that a rise in intracellular calcium induces a change in
the configuration of CaM-KCNQ binding, which leads to the reduction of KCNQ
affinity for PIP2 and subsequent current suppression.
PMID- 24349251
TI - Effects of sustained sleep restriction on mitogen-stimulated cytokines,
chemokines and T helper 1/ T helper 2 balance in humans.
AB - BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular
immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine
profile. Since little is known about more long-term effects, we investigated how
five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1-
and Th2 cytokine secretion. METHODS: Nine healthy males participated in an
experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00
07.00 h) followed by 5 days with restricted sleep (03.00-07.00 h). On the second
baseline day and on the fifth day with restricted sleep, samples were drawn every
third hour for determination of cytokines/chemokines (tumor necrosis factor alpha
(TNF-alpha), interleukin (IL) -1beta, IL-2, IL-4 and monocyte chemoattractant
protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the
mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and
cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced
immune responses in several ways. There was a general decrease of IL-2 production
(p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a
decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown.
Two significant interactions showed that restricted sleep resulted in increased
TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In
addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep
restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL
4 ratio) which is similar to the effects of acute sleep deprivation and
psychological stress. This may have implications for people suffering from
conditions characterized by excessive Th2 activity like in allergic disease, such
as asthma, for whom restricted sleep could have negative consequences.
PMID- 24349253
TI - Computer-based image studies on tumor nests mathematical features of breast
cancer and their clinical prognostic value.
AB - BACKGROUND: The expending and invasive features of tumor nests could reflect the
malignant biological behaviors of breast invasive ductal carcinoma. Useful
information on cancer invasiveness hidden within tumor nests could be extracted
and analyzed by computer image processing and big data analysis. METHODS: Tissue
microarrays from invasive ductal carcinoma (n = 202) were first stained with
cytokeratin by immunohistochemical method to clearly demarcate the tumor nests.
Then an expert-aided computer analysis system was developed to study the
mathematical and geometrical features of the tumor nests. Computer recognition
system and imaging analysis software extracted tumor nests information, and
mathematical features of tumor nests were calculated. The relationship between
tumor nests mathematical parameters and patients' 5-year disease free survival
was studied. RESULTS: There were 8 mathematical parameters extracted by expert
aided computer analysis system. Three mathematical parameters (number,
circularity and total perimeter) with area under curve >0.5 and 4 mathematical
parameters (average area, average perimeter, total area/total perimeter, average
(area/perimeter)) with area under curve <0.5 in ROC analysis were combined into
integrated parameter 1 and integrated parameter 2, respectively. Multivariate
analysis showed that integrated parameter 1 (P = 0.040) was independent
prognostic factor of patients' 5-year disease free survival. The hazard risk
ratio of integrated parameter 1 was 1.454 (HR 95% CI [1.017-2.078]), higher than
that of N stage (HR 1.396, 95% CI [1.125-1.733]) and hormone receptor status (HR
0.575, 95% CI [0.353-0.936]), but lower than that of histological grading (HR
3.370, 95% CI [1.125-5.364]) and T stage (HR 1.610, 95% CI [1.026 -2.527]).
CONCLUSIONS: This study indicated integrated parameter 1 of mathematical features
(number, circularity and total perimeter) of tumor nests could be a useful
parameter to predict the prognosis of early stage breast invasive ductal
carcinoma.
PMID- 24349252
TI - Molecular epidemiologic characterization of a clustering HCV infection caused by
inappropriate medical care in Heyuan City of Guangdong, China.
AB - BACKGROUND: From November 2011 to January 2012, a number of clustering cases of
HCV infection were reported in Zijin County, Heyuan City, Guangdong, China. Most
patients in the clustering cases suspected that they could be infected due to
inappropriate medical care in the clinic located at the Xiangshui road. However,
the molecular epidemiology of the clustering cases remains unknown. METHODOLOGY:
The residents, living at Xiangshui Road, with HCV antibody positive reported from
2011 and 2012 were recruited. A survey of the HCV infected individuals from the
clustering cases was conducted. Each participant underwent a questionnaire
defining demographic characteristics and health care history. HCV serological
test and viral load test were performed to confirm the infection status.
Molecular phylogenetic analysis and Bayesian coalescence analysis were conducted
to further confirm the HCV subtype distribution and to reconstruct the associated
demographic history and time-scaled phylogeny among the clustering cases.
PRINCIPAL FINDINGS: The molecular phylogenetic analysis revealed that only two
HCV subtypes, 2a and 6a, were found among the clustering cases. There was no
close HCV subtype evolutionary relation was observed among patients from the same
family. The 6a cluster showed higher viral loads than the 2a cluster. In
addition, the Bayesian skyline plot analysis showed that both the HCV 2a and 6a
subtype infections among the Heyuan cases experienced an "expansion-diminishment
expansion" featured dissemination. The 2a clustering infection occurred in 2004,
and the 6a clustering cases originated in 2006. CONCLUSIONS: The molecular
epidemiological characters imply that the inappropriate medical practices were
possibly associated with the clustering HCV cases in Heyuan City during 2011,
2012. Latent HCV subtypes 2a and 6a infection may cause the prevalence and become
a new public health issue in Guangdong, China.
PMID- 24349254
TI - Discovery of potent broad spectrum antivirals derived from marine actinobacteria.
AB - Natural products provide a vast array of chemical structures to explore in the
discovery of new medicines. Although secondary metabolites produced by microbes
have been developed to treat a variety of diseases, including bacterial and
fungal infections, to date there has been limited investigation of natural
products with antiviral activity. In this report, we used a phenotypic cell-based
replicon assay coupled with an iterative biochemical fractionation process to
identify, purify, and characterize antiviral compounds produced by marine
microbes. We isolated a compound from Streptomyces kaviengensis, a novel
actinomycetes isolated from marine sediments obtained off the coast of New
Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound
displays potent activity against western equine encephalitis virus in cultured
cells with half-maximal inhibitory concentrations of less than 4 nM and a
selectivity index of greater than 550. Our efforts also revealed that several
antimycin A analogues display antiviral activity, and mechanism of action studies
confirmed that these Streptomyces-derived secondary metabolites function by
inhibiting the cellular mitochondrial electron transport chain, thereby
suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A
functions as a broad spectrum agent with activity against a wide range of RNA
viruses in cultured cells, including members of the Togaviridae, Flaviviridae,
Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we
demonstrate that antimycin A reduces central nervous system viral titers,
improves clinical disease severity, and enhances survival in mice given a lethal
challenge with western equine encephalitis virus. Our results provide conclusive
validation for using natural product resources derived from marine microbes as
source material for antiviral drug discovery, and they indicate that host
mitochondrial electron transport is a viable target for the continued development
of broadly active antiviral compounds.
PMID- 24349255
TI - Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced
apoptosis.
AB - Vacuolating cytotoxin A (VacA) is one of the important virulence factors produced
by H. pylori. VacA induces apoptotic cell death, which is potentiated by ammonia.
VacA also causes cell death by mitochondrial damage, via signaling pathways that
are not fully defined. Our aim was to determine whether endoplasmic reticulum
(ER) stress is associated with VacA-induced mitochondrial dysfunction and
apoptosis. We found that C/EBP homologous protein (CHOP), a key signaling protein
of ER stress-induced apoptosis, was transcriptionally up-regulated following
incubation of gastric epithelial cells with VacA. The effect of VacA on CHOP
induction was significantly enhanced by co-incubation with ammonium chloride.
Phosphorylation of eukaryotic initiation factor 2 (eIF2)-alpha, which is known to
occur downstream of the ER stress sensor PKR-like ER-localized eIF2-alpha kinase
(PERK) and to regulate CHOP expression, was also observed following incubation
with VacA in the presence of ammonium chloride. Knockdown of CHOP by siRNA
resulted in inhibition of VacA-induced apoptosis. Further studies showed that
silencing of the PERK gene with siRNA attenuated VacA-mediated phosphorylation of
eIF2-alpha, CHOP induction, expression of BH3-only protein Bim and Bax
activation, and cell death induced by VacA with ammonium chloride, indicating
that ER stress may lead to mitochondrial dysfunction during VacA-induced
toxicity. Activation of ER stress and up-regulation of BH3-only proteins were
also observed in human H. pylori-infected gastric mucosa. Collectively, this
study reveals a possible association between VacA-induced apoptosis in gastric
epithelial cells, and activation of ER stress in H. pylori-positive gastric
mucosa.
PMID- 24349256
TI - Cerebral autoregulation is minimally influenced by the superior cervical ganglion
in two- week-old lambs, and absent in preterm lambs immediately following
delivery.
AB - Cerebral vessels in the premature newborn brain are well supplied with adrenergic
nerves, stemming from the superior cervical ganglia (SCG), but their role in
regulation of blood flow remains uncertain. To test this function twelve
premature or two-week-old lambs were instrumented with laser Doppler flow probes
in the parietal cortices to measure changes in blood flow during changes in
systemic blood pressure and electrical stimulation of the SCG. In lambs delivered
prematurely at ~129 days gestation cerebral perfusion and driving pressure
demonstrated a direct linear relationship throughout the physiologic range,
indicating lack of autoregulation. In contrast, in lambs two-weeks of age,
surgical removal of one SCG resulted in ipsilateral loss of autoregulation during
pronounced hypertension. Electrical stimulation of one SCG elicited unilateral
increases in cerebral resistance to blood flow in both pre-term and two-week-old
lambs, indicating functioning neural pathways in the instrumented, anesthetized
lambs. We conclude cerebral autoregulation is non-functional in preterm lambs
following cesarean delivery. Adrenergic control of cerebral vascular resistance
becomes effective in newborn lambs within two-weeks after birth but SCG-dependent
autoregulation is essential only during pronounced hypertension, well above the
normal range of blood pressure.
PMID- 24349257
TI - Game-based e-learning is more effective than a conventional instructional method:
a randomized controlled trial with third-year medical students.
AB - BACKGROUND: When compared with more traditional instructional methods, Game-based
e-learning (GbEl) promises a higher motivation of learners by presenting contents
in an interactive, rule-based and competitive way. Most recent systematic reviews
and meta-analysis of studies on Game-based learning and GbEl in the medical
professions have shown limited effects of these instructional methods.
OBJECTIVES: To compare the effectiveness on the learning outcome of a Game-based
e-learning (GbEl) instruction with a conventional script-based instruction in the
teaching of phase contrast microscopy urinalysis under routine training
conditions of undergraduate medical students. METHODS: A randomized controlled
trial was conducted with 145 medical students in their third year of training in
the Department of Urology at the University Medical Center Freiburg, Germany. 82
subjects where allocated for training with an educational adventure-game (GbEl
group) and 69 subjects for conventional training with a written script-based
approach (script group). Learning outcome was measured with a 34 item single
choice test. Students' attitudes were collected by a questionnaire regarding fun
with the training, motivation to continue the training and self-assessment of
acquired knowledge. RESULTS: The students in the GbEl group achieved
significantly better results in the cognitive knowledge test than the students in
the script group: the mean score was 28.6 for the GbEl group and 26.0 for the
script group of a total of 34.0 points with a Cohen's d effect size of 0.71 (ITT
analysis). Attitudes towards the recent learning experience were significantly
more positive with GbEl. Students reported to have more fun while learning with
the game when compared to the script-based approach. CONCLUSIONS: Game-based e
learning is more effective than a script-based approach for the training of
urinalysis in regard to cognitive learning outcome and has a high positive
motivational impact on learning. Game-based e-learning can be used as an
effective teaching method for self-instruction.
PMID- 24349258
TI - Analysis of time-resolved gene expression measurements across individuals.
AB - Genetic and environmental determinants of altered cellular function, disease
state, and drug response are increasingly studied using time-resolved
transcriptomic profiles. While it is widely acknowledged that the rate of
biological processes may vary between individuals, data analysis approaches that
go beyond evaluating differential expression of single genes have so far not
taken this variability into account. To this end, we introduce here a robust
multi-gene data analysis approach and evaluate it in a biomarker discovery
scenario across four publicly available datasets. In our evaluation, existing
methods perform surprisingly poorly on time-resolved data; only the approach
taking the variability into account yields reproducible and biologically
plausible results. Our results indicate the need to capture gene expression
between potentially heterogeneous individuals at multiple time points, and
highlight the importance of robust data analysis in the presence of heterogeneous
gene expression responses.
PMID- 24349259
TI - Investment into defensive traits by anuran prey (Lithobates pipiens) is mediated
by the starvation-predation risk trade-off.
AB - Prey can invest in a variety of defensive traits when balancing risk of predation
against that of starvation. What remains unknown is the relative costs of
different defensive traits and how prey reconcile investment into these traits
when energetically limited. We tested the simple allocation model of prey
defense, which predicts an additive effect of increasing predation risk and
resource availability, resulting in the full deployment of defensive traits under
conditions of high risk and resource saturation. We collected morphometric,
developmental, and behavioural data in an experiment using dragonfly larvae
(predator) and Northern leopard frog tadpoles (prey) subject to variable levels
of food availability and predation risk. Larvae exposed to food restriction
showed limited response to predation risk; larvae at food saturation altered
behaviour, development, and growth in response to predation risk. Responses to
risk varied through time, suggesting ontogeny may affect the deployment of
particular defensive traits. The observed negative correlation between body size
and activity level for food-restricted prey--and the absence of a similar
response among adequately-fed prey--suggests that a trade-off exists between
behavioural and growth responses when energy budgets are limited. Our research is
the first to demonstrate how investment into these defensive traits is mediated
along gradients of both predation risk and resource availability over time. The
interactions we demonstrate between resource availability and risk level on
deployment of inducible defenses provide evidence that both internal condition
and extrinsic risk factors play a critical role in the production of inducible
defenses over time.
PMID- 24349260
TI - Opposing roles of PKA and EPAC in the cAMP-dependent regulation of schwann cell
proliferation and differentiation [corrected].
AB - In Schwann cells (SCs), cyclic adenosine monophosphate (cAMP) not only induces
differentiation into a myelinating SC-related phenotype, but also synergistically
enhances the mitogenic action of growth factors such as neuregulin. To better
understand the molecular mechanism by which cAMP exerts these apparently
contradictory functions, we investigated the role of the two main effectors of
cAMP, protein kinase A (PKA) and the exchange protein activated by cAMP (EPAC),
on the proliferation and differentiation of both isolated and axon-related SCs.
For these studies, a variety of PKA and EPAC agonists and antagonists were used,
including pathway-selective analogs of cAMP and pharmacological inhibitors. Our
studies indicated that the activity of PKA rather than EPAC was required for the
adjuvant effect of cAMP on S-phase entry, whereas the activity of EPAC rather
than PKA was required for SC differentiation and myelin formation. Even though
selective EPAC activation had an overall anti-proliferative effect in SCs, it
failed to drive the expression of Krox-20, a master regulator of myelination, and
that of myelin-specific proteins and lipids, suggesting that EPAC activation was
insufficient to drive a full differentiating response. Interestingly, inhibition
of EPAC activity resulted in a drastic impairment of SC differentiation and
myelin formation but not Krox-20 expression, which indicates an independent
mechanism of Krox-20 regulation in response to cAMP. In conclusion, our data
supports the idea that the outcome of cAMP signaling in SCs depends on the
particular set of effectors activated. Whereas the mitogenic action of cAMP
relies exclusively on PKA activity, the differentiating action of cAMP requires a
PKA-independent (non-canonical) cAMP-specific pathway that is partially
transduced by EPAC.
PMID- 24349261
TI - A glycoprotein in shells of conspecifics induces larval settlement of the Pacific
oyster Crassostrea gigas.
AB - Settlement of larvae of Crassostrea gigas on shell chips (SC) prepared from
shells of 11 different species of mollusks was investigated. Furthermore, the
settlement inducing compound in the shell of C. gigas was extracted and subjected
to various treatments to characterize the chemical cue. C. gigas larvae settled
on SC of all species tested except on Patinopecten yessoensis and Atrina pinnata.
In SC of species that induced C. gigas larvae to settle, settlement was
proportionate to the amount of SC supplied to the larvae. When compared to C.
gigas SC, all species except Crassostrea nippona showed lower settlement inducing
activities, suggesting that the cue may be more abundant or in a more available
form to the larvae in shells of conspecific and C. nippona than in other species.
The settlement inducing activity of C. gigas SC remained intact after antibiotic
treatment. Extraction of C. gigas SC with diethyl ether (Et2O-ex), ethanol (EtOH
ex), and water (Aq-ex) did not induce larval settlement of C. gigas larvae.
However, extraction of C. gigas SC with 2N of hydrochloric acid (HCl-ex) induced
larval settlement that was at the same level as the SC. The settlement inducing
compound in the HCl-ex was stable at 100 degrees C but was destroyed or degraded
after pepsin, trypsin, PNGase F and trifluoromethanesulfonic acid treatments.
This chemical cue eluted between the molecular mass range of 45 and 150 kDa after
gel filtration and revealed a major band at 55 kDa on the SDS-PAGE gel after
staining with Stains-all. Thus, a 55 kDa glycoprotein component in the organic
matrix of C. gigas shells is hypothesized to be the chemical basis of larval
settlement on conspecifics.
PMID- 24349262
TI - Frequency of inappropriate medication prescription in hospitalized elderly
patients in Italy.
AB - BACKGROUND: Older people often need comprehensive treatment, including many
medications, and polypharmacy is common. The aims of this cross-sectional
investigation were to examine the potentially inappropriate medication during the
hospitalization and to identify the factors that may influence such
inappropriateness among elderly in Italy. METHODS: A sample of 605 individuals
aged 65 years and older admitted in non-academic public acute care hospitals was
randomly selected. Prescription of inappropriate medications were evaluated
during the period from the day of admission to a randomly preselected day (index
day). Beers Criteria were used to evaluate appropriateness. RESULTS: At least one
potentially inappropriate medication prescription from the day of hospital
admission to the index day has been observed in 188 patients (31.1%), and
respectively 84.1% and 15.9% of them had received one or two inappropriate
medications. A total of 15 medications was prescribed inappropriately to these
188 patients, for 215 times with a total of 1143 doses. The multivariate logistic
regression analysis revealed that the significant predictors for having at least
one potentially inappropriate medication prescription during the hospitalization
were: patients having an elementary education level, a lower pre-admission
performance-based measure of basic activities of daily living, having received an
inappropriate drug before the hospitalization, a hospital stay in the general and
in the specialties surgical wards, a longer length of hospital stay from the
admission to the index day, and having received a higher number of drugs from the
day of the hospital admission to the index day. The most prevalent inappropriate
medications administered were ketorolac (27.4%), amiodarone (19.1%), and
clonidine (11.2%). CONCLUSIONS: This study supports the need for clinical
guidelines implementation to assist physicians in choosing the most appropriate
drugs for the elderly and for effective education of all physicians.
PMID- 24349263
TI - Phenotypic and genotypic characteristic of invasive pneumococcal isolates from
both children and adult patients from a multicenter surveillance in China 2005
2011.
AB - Streptococcus pneumoniae is an important pathogen in both children and the
elderly, but previous studies in China have provided limited information about
invasive pneumococcal disease (IPD). A total of 240 IPD S. pneumoniae strains
(from 105 children and 135 adults) were collected from 12 cities in China in 2005
2011. Their phenotypes and genetic characteristics were analyzed. Streptococcus
pneumoniae remained highly resistant to macrolides, tetracycline, and
cotrimoxazole each year. Serotypes were assigned to the 240 isolates, and 19A
(22.1%), 19F (21.7%), 14 (7.5%), 3 (7.1%), and 23F (5.4%) were the most
prevalent, accounting for 63.8% of all strains. Serogroup 19 strains were
significantly more common among children than among adults (58.7% vs 32.4%,
respectively; P < 0.001). Serotypes 19F and 19A demonstrated higher resistance to
beta-lactams and cephalosporins than the other serotypes. The coverage of PCV13
was superior to that calculated for PCV7 and PCV10 (77.9% vs 40.8% and 47.1%,
respectively), and coverage was higher in children than in adults (85.6% vs
72.1%, respectively; P = 0.012). A multilocus sequence typing analysis revealed
great diversity, with nine clonal complexes and 83 singletons among all the
strains. Specifically, CC271 was more common in children, whereas singletons were
more prevalent in adults. Among the serogroup 19 strains, 84.7% were ST271,
ST320, or ST236, belonging to CC271. The homogeneous genetic background of 19F
and 19A, together with the high resistance of these strains, suggests that clonal
spread is responsible for the high prevalence of serogroup 19 in IPD. This is the
first large study to investigate IPD strains in both children and adults in
China.
PMID- 24349264
TI - Comparison of ultra-conserved elements in drosophilids and vertebrates.
AB - Metazoan genomes contain many ultra-conserved elements (UCEs), long sequences
identical between distant species. In this study we identified UCEs in
drosophilid and vertebrate species with a similar level of phylogenetic
divergence measured at protein-coding regions, and demonstrated that both the
length and number of UCEs are larger in vertebrates. The proportion of non-exonic
UCEs declines in distant drosophilids whilst an opposite trend was observed in
vertebrates. We generated a set of 2,126 Sophophora UCEs by merging elements
identified in several drosophila species and compared these to the eutherian UCEs
identified in placental mammals. In contrast to vertebrates, the Sophophora UCEs
are depleted around transcription start sites. Analysis of 52,954 P-element,
piggyBac and Minos insertions in the D. melanogaster genome revealed depletion of
the P-element and piggyBac insertions in and around the Sophophora UCEs. We
examined eleven fly strains with transposon insertions into the intergenic UCEs
and identified associated phenotypes in five strains. Four insertions behave as
recessive lethals, and in one case we observed a suppression of the marker gene
within the transgene, presumably by silenced chromatin around the integration
site. To confirm the lethality is caused by integration of transposons we
performed a phenotype rescue experiment for two stocks and demonstrated that the
excision of the transposons from the intergenic UCEs restores viability.
Sequencing of DNA after the transposon excision in one fly strain with the
restored viability revealed a 47 bp insertion at the original transposon
integration site suggesting that the nature of the mutation is important for the
appearance of the phenotype. Our results suggest that the UCEs in flies and
vertebrates have both common and distinct features, and demonstrate that a
significant proportion of intergenic drosophila UCEs are sensitive to disruption.
PMID- 24349265
TI - Resistance to bleomycin in cancer cell lines is characterized by prolonged
doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.
AB - BACKGROUND: To establish, characterize and elucidate potential mechanisms of
acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM
resistant cell lines were established by exposure to escalating BLM
concentrations over a period of 16-24 months. IC50 values and cell doubling times
were quantified using a real time cytotoxicity assay. COMET and gamma-H2AX
assays, cell cycle analysis, and apoptosis assessment further investigated the
mechanisms of BLM resistance in these cell lines. RESULTS: Compared with parental
cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50
and a mean doubling time increase of 147 % (range 64 %-352%) in BLM-resistant sub
clones (p<0.05 for both). Higher maintenance BLM concentrations were associated
with higher IC50 and increased doubling times (p<0.05). Significantly reduced DNA
damage (COMET and gamma-H2AX assays), G2/M arrest, and apoptosis (p<0.05 for each
set of comparison) following high-dose acute BLM exposure was observed in
resistant sub-clones, compared with their BLM-sensitive parental counterparts.
Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity
in 3/7 BLM-resistant sub-clones (p<0.05). CONCLUSION: Bleomycin resistance may be
associated with reduced DNA damage after bleomycin exposure, resulting in reduced
G2/M arrest, and reduced apoptosis.
PMID- 24349266
TI - Changes in mitochondrial carriers exhibit stress-specific signatures in INS
1Ebeta-cells exposed to glucose versus fatty acids.
AB - Chronic exposure of beta-cells to metabolic stresses impairs their function and
potentially induces apoptosis. Mitochondria play a central role in coupling
glucose metabolism to insulin secretion. However, little is known on
mitochondrial responses to specific stresses; i.e. low versus high glucose,
saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were
exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM
oleate. Culture at standard 11.1 mM glucose served as no-stress control and
transient oxidative stress (200 uM H2O2 for 10 min at day 0) served as positive
stressful condition. Mito-array analyzed transcripts of 60 mitochondrion
associated genes with special focus on members of the Slc25 family. Transcripts
of interest were evaluated at the protein level by immunoblotting. Bioinformatics
analyzed the expression profiles to delineate comprehensive networks. Chronic
exposure to the different metabolic stresses impaired glucose-stimulated insulin
secretion; revealing glucotoxicity and lipo-dysfunction. Both saturated and
unsaturated fatty acids increased expression of the carnitine/acylcarnitine
carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were
specifically upregulated by palmitate and oleate, respectively. High glucose
upregulated CIC, the dicarboxylate carrier DIC and glutamate carrier GC1.
Conversely, it reduced expression of energy sensors (AMPK, SIRT1, SIRT4),
metabolic genes, transcription factor PDX1, and anti-apoptotic Bcl2. This was
associated with caspase-3 cleavage and cell death. Expression levels of GC1 and
SIRT4 exhibited positive and negative glucose dose-response, respectively.
Expression profiles of energy sensors and mitochondrial carriers were selectively
modified by the different conditions, exhibiting stress-specific signatures.
PMID- 24349267
TI - Recording of severe mental illness in United Kingdom primary care, 2000-2010.
AB - BACKGROUND: There is increasing emphasis on primary care services for individuals
with severe mental illnesses (SMI), including schizophrenia, bipolar disorder,
and other non-organic psychotic disorders. However we lack information on how
many people receive these different diagnoses in primary care. Primary care
databases offer an opportunity to explore the recording of new SMI diagnoses in
representative general practices. METHODS: We used data from The UK Health
Improvement Network (THIN) primary care database including longitudinal patient
records for individuals aged over 16 years from 437 general practices. We
determined the annual GP recorded rate of first diagnosis of SMI by age, gender,
social deprivation and urbanicity between 2000 and 2010. RESULTS: We identified
10,520 individuals with a first record of schizophrenia, bipolar disorder or
other non-organic psychosis among 4,164,794 patients. This corresponded to a rate
of first diagnosis of 46.4 per 100,000 person years at risk (PYAR) (95% CI 45.4
to 47.4) in the 16-65 age group. The rate of first record of schizophrenia was
9.2 per 100,000 PYAR (95% CI 8.7 to 9.6) in this age group, bipolar disorder was
15.0 per 100,000 PYAR (95% CI 14.4 to 15.5) and other non-organic psychotic
disorder was 22.3 per 100,000 PYAR (95% CI 21.6 to 23.0). CONCLUSIONS: The rates
of GP recorded SMI in primary care records were broadly comparable to incidence
rates from previous epidemiological studies of SMI and show similar patterns by
socio-demographic characteristics. However there were some differences by
specific diagnoses. GPs may be recording rates that are higher than those used to
commission services.
PMID- 24349269
TI - Recreational boats and turtles: behavioral mismatches result in high rates of
injury.
AB - Recreational boats are a dominant feature of estuarine waters in the United
States. Boat strike injury and mortality may have a detrimental effect on
populations of diamondback terrapins (Malaclemys terrapin), a keystone species in
estuarine ecosystems. In Barnegat Bay, New Jersey, 11% of terrapins (n = 2,644)
have scars consistent with injuries from boats. Conservative estimates of injury
rates from boats increased from 2006 to 2011. When exposed to playback recordings
of approaching boat engines of varying sizes and speeds in situ, terrapins did
not significantly change their behavior in response to sounds of boat engines of
different sizes. The lack of behavioral response of terrapins to boat sounds
helps explain high rates of injury and mortality of terrapins and may threaten
the viability of terrapin populations. Boater education courses that discuss
impacts of boats to wildlife, combined with closure of areas of high terrapin
densities to boating, are necessary to protect terrapins and other aquatic
species from injury and mortality caused by motorized boats.
PMID- 24349268
TI - Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma.
AB - BACKGROUND: Asthma is a complex and heterogeneous chronic inflammatory disorder
that is associated with mucous cell metaplasia and mucus hypersecretion.
Functional genomic analysis indicates that mucous cell metaplasia and mucus
hypersecretion depend on members of the calcium-activated chloride channel (CLCA)
gene family. It has been reported that the inhibition of CLCAs could relieve the
symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to
treat allergic diseases such as asthma. METHODS: We constructed asthmatic mouse
models of OVA-induced chronic airway inflammatory disorder to study the function
of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet
cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac,
IL-13, IFN-gamma levels in bronchoalveolar lavage fluid (BALF) were examined by
ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue
staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western
blotting and immunohistochemical analysis. RESULTS: In our study, mice treated
with mCLCA3 antibody developed fewer pathological changes compared with control
mice and asthmatic mice, including a remarkable reduction in airway inflammation,
the number of goblet cells and mCLCA3 expression in lung tissue. The levels of
muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate
of goblet cell apoptosis was increased after treatment with mCLCA3 antibody,
which was accompanied by an increase in Bax levels and a decrease in Bcl-2
expression in goblet cells. CONCLUSIONS: Taken together, our results indicate
that mCLCA3 antibody may have the potential as an effective pharmacotherapy for
asthma.
PMID- 24349270
TI - Immunomagnetic separation combined with polymerase chain reaction for the
detection of Alicyclobacillus acidoterrestris in apple juice.
AB - A combination of immunomagnetic separation (IMS) and polymerase chain reaction
(PCR) was used to detect Alicyclobacillus acidoterrestris (A. acidoterrestris) in
apple juice. The optimum technological parameters of the IMS system were
investigated. The results indicated that the immunocapture reactions could be
finished in 60 min and the quantity of IMPs used for IMS was 2.5 mg/mL. Then the
combined IMS-PCR procedure was assessed by detecting A. acidoterrestris in apple
juice samples. The agarose gel electrophoresis results of 20 different strains
showed that the IMS-PCR procedure presented high specificity to the A.
acidoterrestris. The sensitivity of the IMS-PCR was 2*10(1) CFU/mL and the total
detection time was 3 to 4 h. Of the 78 naturally contaminated apple juice samples
examined, the sensitivity, specificity and accuracy of IMS-PCR compared with the
standardized pour plate method were 90.9%, 97.0% and 96.2%, respectively. The
results exhibited that the developed IMS-PCR method will be a valuable tool for
detecting A. acidoterrestris and improving food quality in juice samples.
PMID- 24349271
TI - Prediction of severe disease in children with diarrhea in a resource-limited
setting.
AB - OBJECTIVE: To investigate the accuracy of three clinical scales for predicting
severe disease (severe dehydration or death) in children with diarrhea in a
resource-limited setting. METHODS: Participants included 178 children admitted to
three Rwandan hospitals with diarrhea. A local physician or nurse assessed each
child on arrival using the World Health Organization (WHO) severe dehydration
scale and the Centers for Disease Control (CDC) scale. Children were weighed on
arrival and daily until they achieved a stable weight, with a 10% increase
between admission weight and stable weight considered severe dehydration. The
Clinical Dehydration Scale was then constructed post-hoc using the data collected
for the other two scales. Receiver Operator Characteristic (ROC) curves were
constructed for each scale compared to the composite outcome of severe
dehydration or death. RESULTS: The WHO severe dehydration scale, CDC scale, and
Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI
0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89),
respectively, in the full cohort. Only the Clinical Dehydration Scale was a
significant predictor of severe disease when used in infants, with an AUC of 0.77
(95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63,
0.93). CONCLUSIONS: While all three scales were moderate predictors of severe
disease in children with diarrhea, scale accuracy varied based on provider
training and age of the child. Future research should focus on developing or
validating clinical tools that can be used accurately by nurses and other less
skilled providers to assess all children with diarrhea in resource-limited
settings.
PMID- 24349272
TI - Efficient isolation of pure and functional mitochondria from mouse tissues using
automated tissue disruption and enrichment with anti-TOM22 magnetic beads.
AB - To better understand molecular mechanisms regulating changes in metabolism, as
observed e.g. in diabetes or neuronal disorders, the function of mitochondria
needs to be precisely determined. The usual isolation methods such as
differential centrifugation result in isolates of highly variable quality and
quantity. To fulfill the need of a reproducible isolation method from solid
tissues, which is suitable to handle parallel samples simultaneously, we
developed a protocol based on anti-TOM22 (translocase of outer mitochondrial
membrane 22 homolog) antibody-coupled magnetic beads. To measure oxygen
consumption rate in isolated mitochondria from various mouse tissues, a
traditional Clark electrode and the high-throughput XF Extracellular Flux
Analyzer were used. Furthermore, Western blots, transmission electron microscopic
and proteomic studies were performed to analyze the purity and integrity of the
mitochondrial preparations. Mitochondrial fractions isolated from liver, brain
and skeletal muscle by anti-TOM22 magnetic beads showed oxygen consumption
capacities comparable to previously reported values and little contamination with
other organelles. The purity and quality of isolated mitochondria using anti
TOM22 magnetic beads was compared to traditional differential centrifugation
protocol in liver and the results indicated an obvious advantage of the magnetic
beads method compared to the traditional differential centrifugation technique.
PMID- 24349273
TI - Application of U/Th and 40Ar/39Ar dating to Orgnac 3, a Late Acheulean and Early
Middle Palaeolithic site in Ardeche, France.
AB - Refined radio-isotopic dating techniques have been applied to Orgnac 3, a Late
Acheulean and Early Middle Palaeolithic site in France. Evidence of Levallois
core technology appeared in level 4b in the middle of the sequence, became
predominant in the upper horizons, and was best represented in uppermost level 1,
making the site one of the oldest examples of Levallois technology. In our dating
study, fourteen speleothem samples from levels 7, 6 and 5b, were U/Th-dated. Four
pure calcite samples from the speleothem PL1 (levels 5b, 6) yield ages between
265 +/- 4 (PL1-3) and 312 +/- 15 (PL1-6) thousand years ago (ka). Three samples
from the top of a second stalagmite, PL2, yield dates ranging from 288 +/- 10 ka
(PL2-1) to 298 +/- 17 ka (PL2-3). Three samples from the base of PL2 (level 7)
yield much younger U/Th dates between 267 and 283 ka. These dates show that the
speleothems PL1 and PL2 are contemporaneous and formed during marine isotope
stage (MIS) 9 and MIS 8. Volcanic minerals in level 2, the upper sequence, were
dated by the (40)Ar/(39)Ar method, giving a weighted mean of 302.9 +/- 2.5 ka
(2sigma) and an inverse isochron age of 302.9 +/- 5.9 ka (2sigma). Both
(40)Ar/(39)Ar dating of volcanic sanidines and U/Th dating of relatively pure and
dense cave calcites are known to be well established. The first parallel
application of the two geochronometers to Orgnac 3 yields generally consistent
results, which point to the reliability of the two methods. The difference
between their age results is discussed.
PMID- 24349274
TI - Rbt1 protein domains analysis in Candida albicans brings insights into hyphal
surface modifications and Rbt1 potential role during adhesion and biofilm
formation.
AB - Cell wall proteins are central to the virulence of Candida albicans. Hwp1, Hwp2
and Rbt1 form a family of hypha-associated cell surface proteins. Hwp1 and Hwp2
have been involved in adhesion and other virulence traits but Rbt1 is still
poorly characterized. To assess the role of Rbt1 in the interaction of C.
albicans with biotic and abiotic surfaces independently of its morphological
state, heterologous expression and promoter swap strategies were applied. The N
terminal domain with features typical of the Flo11 superfamily was found to be
essential for adhesiveness to polystyrene through an increase in cell surface
hydrophobicity. A 42 amino acid-long domain localized in the central part of the
protein was shown to enhance the aggregation function. We demonstrated that a
VTTGVVVVT motif within the 42 amino acid domain displayed a high beta-aggregation
potential and was responsible for cell-to-cell interactions by promoting the
aggregation of hyphae. Finally, we showed through constitutive expression that
while Rbt1 was directly accessible to antibodies in hyphae, it was not so in
yeast. Similar results were obtained for another cell wall protein, namely Iff8,
and suggested that modification of the cell wall structure between yeast and
hyphae can regulate the extracellular accessibility of cell wall proteins
independently of gene regulation.
PMID- 24349275
TI - Myelopoietic efficacy of orlistat in murine hosts bearing T cell lymphoma:
implication in macrophage differentiation and activation.
AB - Orlistat, an inhibitor of fatty acid synthase (FASN), acts as an antitumor agent
by blocking de novo fatty acid synthesis of tumor cells. Although, myelopoiesis
also depends on de novo fatty acid synthesis, the effect of orlistat on
differentiation of macrophages, which play a central role in host's antitumor
defence, remains unexplored in a tumor-bearing host. Therefore, the present
investigation was undertaken to examine the effect of orlistat administration on
macrophage differentiation in a T cell lymphoma bearing host. Administration of
orlistat (240 mg/kg/day/mice) to tumor-bearing mice resulted in a decline of
tumor load accompanied by an augmentation of bone marrow cellularity and survival
of bone marrow cells (BMC). The expression of apoptosis regulatory caspase-3, Bax
and Bcl2 was modulated in the BMC of orlistat-administered tumor-bearing mice.
Orlistat administration also resulted in an increase in serum level of IFN-gamma
along with decreased TGF-beta and IL-10. BMC of orlistat-administered tumor
bearing mice showed augmented differentiation into macrophages accompanied by
enhanced expression of macrophage colony stimulating factor (M-CSF) and its
receptor (M-CSFR). The macrophages differentiated from BMC of orlistat
administered mice showed characteristic features of M1 macrophage phenotype
confirmed by expression of CD11c, TLR-2, generation of reactive oxygen species,
phagocytosis, tumor cell cytotoxicity, production of IL-1,TNF-alpha and nitric
oxide. These novel findings indicate that orlistat could be useful to support
myelopoesis in a tumor-bearing host.
PMID- 24349276
TI - Biochemical, transcriptional and translational evidences of the phenol-meta
degradation pathway by the hyperthermophilic Sulfolobus solfataricus 98/2.
AB - Phenol is a widespread pollutant and a model molecule to study the biodegradation
of monoaromatic compounds. After a first oxidation step leading to catechol in
mesophilic and thermophilic microorganisms, two main routes have been identified
depending on the cleavage of the aromatic ring: ortho involving a catechol 1,2
dioxygenase (C12D) and meta involving a catechol 2,3 dioxygenase (C23D). Our work
aimed at elucidating the phenol-degradation pathway in the hyperthermophilic
archaea Sulfolobus solfataricus 98/2. For this purpose, the strain was cultivated
in a fermentor under different substrate and oxygenation conditions. Indeed,
reducing dissolved-oxygen concentration allowed slowing down phenol catabolism
(specific growth and phenol-consumption rates dropped 55% and 39%, respectively)
and thus, evidencing intermediate accumulations in the broth. HPLC/Diode Array
Detector and LC-MS analyses on culture samples at low dissolved-oxygen
concentration (DOC = 0.06 mg x L(-1)) suggested, apart for catechol, the
presence of 2-hydroxymuconic acid, 4-oxalocrotonate and 4-hydroxy-2-oxovalerate,
three intermediates of the meta route. RT-PCR analysis on oxygenase-coding genes
of S. solfataricus 98/2 showed that the gene coding for the C23D was expressed
only on phenol. In 2D-DIGE/MALDI-TOF analysis, the C23D was found and identified
only on phenol. This set of results allowed us concluding that S. solfataricus
98/2 degrade phenol through the meta route.
PMID- 24349277
TI - Multiview locally linear embedding for effective medical image retrieval.
AB - Content-based medical image retrieval continues to gain attention for its
potential to assist radiological image interpretation and decision making. Many
approaches have been proposed to improve the performance of medical image
retrieval system, among which visual features such as SIFT, LBP, and intensity
histogram play a critical role. Typically, these features are concatenated into a
long vector to represent medical images, and thus traditional dimension reduction
techniques such as locally linear embedding (LLE), principal component analysis
(PCA), or laplacian eigenmaps (LE) can be employed to reduce the "curse of
dimensionality". Though these approaches show promising performance for medical
image retrieval, the feature-concatenating method ignores the fact that different
features have distinct physical meanings. In this paper, we propose a new method
called multiview locally linear embedding (MLLE) for medical image retrieval.
Following the patch alignment framework, MLLE preserves the geometric structure
of the local patch in each feature space according to the LLE criterion. To
explore complementary properties among a range of features, MLLE assigns
different weights to local patches from different feature spaces. Finally, MLLE
employs global coordinate alignment and alternating optimization techniques to
learn a smooth low-dimensional embedding from different features. To justify the
effectiveness of MLLE for medical image retrieval, we compare it with
conventional spectral embedding methods. We conduct experiments on a subset of
the IRMA medical image data set. Evaluation results show that MLLE outperforms
state-of-the-art dimension reduction methods.
PMID- 24349278
TI - BP-ANN for fitting the temperature-germination model and its application in
predicting sowing time and region for Bermudagrass.
AB - Temperature is one of the most significant environmental factors that affects
germination of grass seeds. Reliable prediction of the optimal temperature for
seed germination is crucial for determining the suitable regions and favorable
sowing timing for turf grass cultivation. In this study, a back-propagation
artificial-neural-network-aided dual quintic equation (BP-ANN-QE) model was
developed to improve the prediction of the optimal temperature for seed
germination. This BP-ANN-QE model was used to determine optimal sowing times and
suitable regions for three Cynodon dactylon cultivars (C. dactylon, 'Savannah'
and 'Princess VII'). Prediction of the optimal temperature for these seeds was
based on comprehensive germination tests using 36 day/night (high/low)
temperature regimes (both ranging from 5/5 to 40/40 degrees C with 5 degrees C
increments). Seed germination data from these temperature regimes were used to
construct temperature-germination correlation models for estimating germination
percentage with confidence intervals. Our tests revealed that the optimal
high/low temperature regimes required for all the three bermudagrass cultivars
are 30/5, 30/10, 35/5, 35/10, 35/15, 35/20, 40/15 and 40/20 degrees C; constant
temperatures ranging from 5 to 40 degrees C inhibited the germination of all
three cultivars. While comparing different simulating methods, including DQEM,
Bisquare ANN-QE, and BP-ANN-QE in establishing temperature based germination
percentage rules, we found that the R(2) values of germination prediction
function could be significantly improved from about 0.6940-0.8177 (DQEM approach)
to 0.9439-0.9813 (BP-ANN-QE). These results indicated that our BP-ANN-QE model
has better performance than the rests of the compared models. Furthermore, data
of the national temperature grids generated from monthly-average temperature for
25 years were fit into these functions and we were able to map the germination
percentage of these C. dactylon cultivars in the national scale of China, and
suggested the optimum sowing regions and times for them.
PMID- 24349279
TI - Transformation of adaptation and gain rescaling along the whisker sensory
pathway.
AB - Neurons in all sensory systems have a remarkable ability to adapt their
sensitivity to the statistical structure of the sensory signals to which they are
tuned. In the barrel cortex, firing rate adapts to the variance of a whisker
stimulus and neuronal sensitivity (gain) adjusts in inverse proportion to the
stimulus standard deviation. To determine how adaptation might be transformed
across the ascending lemniscal pathway, we measured the responses of single units
in the first and last subcortical stages, the trigeminal ganglion (TRG) and
ventral posterior medial thalamic nucleus (VPM), to controlled whisker
stimulation in urethane-anesthetized rats. We probed adaptation using a filtered
white noise stimulus that switched between low- and high-variance epochs. We
found that the firing rate of both TRG and VPM neurons adapted to stimulus
variance. By fitting the responses of each unit to a Linear-Nonlinear-Poisson
model, we tested whether adaptation changed feature selectivity and/or
sensitivity. We found that, whereas feature selectivity was unaffected by
stimulus variance, units often exhibited a marked change in sensitivity. The
extent of these sensitivity changes increased systematically along the pathway
from TRG to barrel cortex. However, there was marked variability across units,
especially in VPM. In sum, in the whisker system, the adaptation properties of
subcortical neurons are surprisingly diverse. The significance of this diversity
may be that it contributes to a rich population representation of whisker
dynamics.
PMID- 24349280
TI - Disconnection mechanism and regional cortical atrophy contribute to impaired
processing of facial expressions and theory of mind in multiple sclerosis: a
structural MRI study.
AB - Successful socialization requires the ability of understanding of others' mental
states. This ability called as mentalization (Theory of Mind) may become
deficient and contribute to everyday life difficulties in multiple sclerosis. We
aimed to explore the impact of brain pathology on mentalization performance in
multiple sclerosis. Mentalization performance of 49 patients with multiple
sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2
weighted three-dimensional brain MRI images were acquired at 3Tesla from patients
with multiple sclerosis and 18 gender- and age matched healthy controls. We
assessed overall brain cortical thickness in patients with multiple sclerosis and
the scanned healthy controls, and measured the total and regional T1 and T2 white
matter lesion volumes in patients with multiple sclerosis. Performances in tests
of recognition of mental states and emotions from facial expressions and eye
gazes correlated with both total T1-lesion load and regional T1-lesion load of
association fiber tracts interconnecting cortical regions related to visual and
emotion processing (genu and splenium of corpus callosum, right inferior
longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate
fasciculus). Both of these tests showed correlations with specific cortical areas
involved in emotion recognition from facial expressions (right and left fusiform
face area, frontal eye filed), processing of emotions (right entorhinal cortex)
and socially relevant information (left temporal pole). Thus, both disconnection
mechanism due to white matter lesions and cortical thinning of specific brain
areas may result in cognitive deficit in multiple sclerosis affecting emotion and
mental state processing from facial expressions and contributing to everyday and
social life difficulties of these patients.
PMID- 24349281
TI - Mutation inactivation of Nijmegen breakage syndrome gene (NBS1) in hepatocellular
carcinoma and intrahepatic cholangiocarcinoma.
AB - Nijmegen breakage syndrome (NBS) with NBS1 germ-line mutation is a human
autosomal recessive disease characterized by genomic instability and enhanced
cancer predisposition. The NBS1 gene codes for a protein, Nbs1(p95/Nibrin),
involved in the processing/repair of DNA double-strand breaks. Hepatocellular
carcinoma (HCC) is a complex and heterogeneous tumor with several genomic
alterations. Recent studies have shown that heterozygous NBS1 mice exhibited a
higher incidence of HCC than did wild-type mice. The objective of the present
study is to assess whether NBS1 mutations play a role in the pathogenesis of
human primary liver cancer, including HBV-associated HCC and intrahepatic
cholangiocarcinoma (ICC). Eight missense NBS1 mutations were identified in six of
64 (9.4%) HCCs and two of 18 (11.1%) ICCs, whereas only one synonymous mutation
was found in 89 control cases of cirrhosis and chronic hepatitis B. Analysis of
the functional consequences of the identified NBS1 mutations in Mre11-binding
domain showed loss of nuclear localization of Nbs1 partner Mre11, one of the
hallmarks for Nbs1 deficiency, in one HCC and two ICCs with NBS1 mutations.
Moreover, seven of the eight tumors with NBS1 mutations had at least one genetic
alteration in the TP53 pathway, including TP53 mutation, MDM2 amplification,
p14ARF homozygous deletion and promoter methylation, implying a synergistic
effect of Nbs1 disruption and p53 inactivation. Our findings provide novel
insight on the molecular pathogenesis of primary liver cancer characterized by
mutation inactivation of NBS1, a DNA repair associated gene.
PMID- 24349282
TI - Organic production enhances milk nutritional quality by shifting fatty acid
composition: a United States-wide, 18-month study.
AB - Over the last century, intakes of omega-6 (omega-6) fatty acids in Western diets
have dramatically increased, while omega-3 (omega-3) intakes have fallen.
Resulting omega-6/omega-3 intake ratios have risen to nutritionally undesirable
levels, generally 10 to 15, compared to a possible optimal ratio near 2.3. We
report results of the first large-scale, nationwide study of fatty acids in U.S.
organic and conventional milk. Averaged over 12 months, organic milk contained
25% less omega-6 fatty acids and 62% more omega-3 fatty acids than conventional
milk, yielding a 2.5-fold higher omega-6/omega-3 ratio in conventional compared
to organic milk (5.77 vs. 2.28). All individual omega-3 fatty acid concentrations
were higher in organic milk--alpha-linolenic acid (by 60%), eicosapentaenoic acid
(32%), and docosapentaenoic acid (19%)--as was the concentration of conjugated
linoleic acid (18%). We report mostly moderate regional and seasonal variability
in milk fatty acid profiles. Hypothetical diets of adult women were modeled to
assess milk fatty-acid-driven differences in overall dietary omega-6/omega-3
ratios. Diets varied according to three choices: high instead of moderate dairy
consumption; organic vs. conventional dairy products; and reduced vs. typical
consumption of omega-6 fatty acids. The three choices together would decrease the
omega-6/omega-3 ratio among adult women by ~80% of the total decrease needed to
reach a target ratio of 2.3, with relative impact "switch to low omega-6 foods" >
"switch to organic dairy products" ~ "increase consumption of conventional dairy
products." Based on recommended servings of dairy products and seafoods, dairy
products supply far more alpha-linolenic acid than seafoods, about one-third as
much eicosapentaenoic acid, and slightly more docosapentaenoic acid, but
negligible docosahexaenoic acid. We conclude that consumers have viable options
to reduce average omega-6/omega-3 intake ratios, thereby reducing or eliminating
probable risk factors for a wide range of developmental and chronic health
problems.
PMID- 24349283
TI - Succession of ephemeral secondary forests and their limited role for the
conservation of floristic diversity in a human-modified tropical landscape.
AB - Both local- and landscape-scale processes drive succession of secondary forests
in human-modified tropical landscapes. Nonetheless, until recently successional
changes in composition and diversity have been predominantly studied at the patch
level. Here, we used a unique dataset with 45 randomly selected sites across a
mixed-use tropical landscape in central Panama to study forest succession
simultaneously on local and landscape scales and across both life stages
(seedling, sapling, juvenile and adult trees) and life forms (shrubs, trees,
lianas, and palms). To understand the potential of these secondary forests to
conserve tree species diversity, we also evaluated the diversity of species that
can persist as viable metapopulations in a dynamic patchwork of short-lived
successional forests, using different assumptions about the average relative size
at reproductive maturity. We found a deterministic shift in the diversity and
composition of the local plant communities as well as the metacommunity, driven
by variation in the rate at which species recruited into and disappeared from the
secondary forests across the landscape. Our results indicate that dispersal
limitation and the successional niche operate simultaneously and shape
successional dynamics of the metacommunity of these early secondary forests. A
high diversity of plant species across the metacommunity of early secondary
forests shows a potential for restoration of diverse forests through natural
succession, when trees and fragments of older forests are maintained in the
agricultural matrix and land is abandoned or set aside for a long period of time.
On the other hand, during the first 32 years the number of species with mature
sized individuals was a relatively small and strongly biased sub-sample of the
total species pool. This implies that ephemeral secondary forests have a limited
role in the long-term conservation of tree species diversity in human-modified
tropical landscapes.
PMID- 24349284
TI - Tuberculosis in migrant populations. A systematic review of the qualitative
literature.
AB - BACKGROUND: The re-emergence of tuberculosis (TB) in low-incidence countries and
its disproportionate burden on immigrants is a public health concern posing
specific social and ethical challenges. This review explores perceptions,
knowledge, attitudes and treatment adherence behaviour relating to TB and their
social implications as reported in the qualitative literature. METHODS:
Systematic review in four electronic databases. Findings from thirty selected
studies extracted, tabulated, compared and synthesized. FINDINGS: TB was
attributed to many non-exclusive causes including air-born transmission of
bacteria, genetics, malnutrition, excessive work, irresponsible lifestyles,
casual contact with infected persons or objects; and exposure to low
temperatures, dirt, stress and witchcraft. Perceived as curable but potentially
lethal and highly contagious, there was confusion around a condition surrounded
by fears. A range of economic, legislative, cultural, social and health system
barriers could delay treatment seeking. Fears of deportation and having contacts
traced could prevent individuals from seeking medical assistance. Once on
treatment, family support and "the personal touch" of health providers emerged as
key factors facilitating adherence. The concept of latent infection was difficult
to comprehend and while TB screening was often seen as a socially responsible
act, it could be perceived as discriminatory. Immigration and the infectiousness
of TB mutually reinforced each another exacerbating stigma. This was further
aggravated by indirect costs such as losing a job, being evicted by a landlord or
not being able to attend school. CONCLUSIONS: Understanding immigrants' views of
TB and the obstacles that they face when accessing the health system and adhering
to a treatment programme-taking into consideration their previous experiences at
countries of origin as well as the social, economic and legislative context in
which they live at host countries- has an important role and should be considered
in the design, evaluation and adaptation of programmes.
PMID- 24349285
TI - The rhizosphere selects for particular groups of acidobacteria and
verrucomicrobia.
AB - There is a lack in our current understanding on the putative interactions of
species of the phyla of Acidobacteria and Verrucomicrobia with plants. Moreover,
progress in this area is seriously hampered by the recalcitrance of members of
these phyla to grow as pure cultures. The purpose of this study was to
investigate whether particular members of Acidobacteria and Verrucomicrobia are
avid colonizers of the rhizosphere. Based on previous work, rhizosphere
competence was demonstrated for the Verrucomicrobia subdivision 1 groups of
Luteolibacter and Candidatus genus Rhizospheria and it was hypothesized that the
rhizosphere is a common habitat for Acidobacteria subdivision 8 (class
Holophagae). We assessed the population densities of Bacteria, Verrucomicrobia
subdivision 1 groups Luteolibacter and Candidatus genus Rhizospheria and
Acidobacteria subdivisions 1, 3, 4, 6 and Holophagae in bulk soil and in the
rhizospheres of grass, potato and leek in the same field at different points in
time using real-time quantitative PCR. Primers of all seven verrucomicrobial,
acidobacterial and holophagal PCR systems were based on 16S rRNA gene sequences
of cultivable representatives of the different groups. Luteolibacter, Candidatus
genus Rhizospheria, subdivision 6 acidobacteria and Holophaga showed preferences
for one or more rhizospheres. In particular, the Holophaga 16S rRNA gene number
were more abundant in the leek rhizosphere than in bulk soil and the rhizospheres
of grass and potato. Attraction to, and colonization of, leek roots by Holophagae
strain CHC25 was further shown in an experimental microcosm set-up. In the light
of this remarkable capacity, we propose to coin strain CHC25 Candidatus
Porrumbacterium oxyphilus (class Holophagae, Phylum Acidobacteria), the first
cultured representative with rhizosphere competence.
PMID- 24349286
TI - Arabidopsis heterotrimeric G-proteins play a critical role in host and nonhost
resistance against Pseudomonas syringae pathogens.
AB - Heterotrimeric G-proteins have been proposed to be involved in many aspects of
plant disease resistance but their precise role in mediating nonhost disease
resistance is not well understood. We evaluated the roles of specific subunits of
heterotrimeric G-proteins using knock-out mutants of Arabidopsis Galpha, Gbeta
and Ggamma subunits in response to host and nonhost Pseudomonas pathogens. Plants
lacking functional Galpha, Gbeta and Ggamma1Ggamma2 proteins displayed enhanced
bacterial growth and disease susceptibility in response to host and nonhost
pathogens. Mutations of single Ggamma subunits Ggamma1, Ggamma2 and Ggamma3 did
not alter bacterial disease resistance. Some specificity of subunit usage was
observed when comparing host pathogen versus nonhost pathogen. Overexpression of
both Galpha and Gbeta led to reduced bacterial multiplication of nonhost pathogen
P. syringae pv. tabaci whereas overexpression of Gbeta, but not of Galpha,
resulted in reduced bacterial growth of host pathogen P. syringae pv. maculicola,
compared to wild-type Col-0. Moreover, the regulation of stomatal aperture by
bacterial pathogens was altered in Galpha and Gbeta mutants but not in any of the
single or double Ggamma mutants. Taken together, these data substantiate the
critical role of heterotrimeric G-proteins in plant innate immunity and stomatal
modulation in response to P. syringae.
PMID- 24349287
TI - Predicting early intrahepatic recurrence of hepatocellular carcinoma after
microwave ablation using SELDI-TOF proteomic signature.
AB - BACKGROUND/AIMS: Despite great progress in the treatment of hepatocellular
carcinoma (HCC) over the last-decade, intrahepatic recurrence is still the most
frequent serious adverse event after all the treatments including microwave
ablation. This study aimed to predict early recurrence of HCC after microwave
ablation using serum proteomic signature. METHODS: After curative microwave
ablation of HCC, 86 patients were followed-up for 1 year. Serum samples were
collected before microwave ablation. The mass spectra of proteins were generated
using surface-enhanced laser desorption/ionization time-of-flight mass
spectrometry (SELDI-TOF MS). Serum samples from 50 patients were randomly
selected as a training set and for biomarkers discovery and model development.
The remaining serum samples were categorized for validation of the algorithm.
RESULTS: According to preablation serum protein profiling obtained from the 50
HCC samples in the training set, nine significant differentially-expressed
proteins were detected in the serum samples between recurrent and non-recurrent
patients. Decision classification tree combined with three candidate proteins
with m/z values of 7787, 6858 and 6646 was produced using Biomarker Patterns
Software with sensitivity of 85.7% and specificity of 88.9% in the training set.
When the SELDI marker pattern was tested with the blinded testing set, it yielded
a sensitivity of 80.0%, a specificity of 88.5% and a positive predictive value of
86.1%. CONCLUSIONS: Differentially-expressed protein peaks in preablation serum
screened by SELDI are associated with prognosis of HCC. The decision
classification tree is a potential tool in predicting early intrahepatic
recurrence in HCC patients after microwave ablation.
PMID- 24349288
TI - A decline in HIV and syphilis epidemics in Chinese female sex workers (2000
2011): a systematic review and meta-analysis.
AB - BACKGROUND: Female sex workers (FSWs) play an important role in transmitting HIV
and syphilis from high-risk groups to the general population. However, the trends
in HIV and syphilis epidemics in Chinese FSWs in the period after 2000 are
unclear to date. METHODS: The Preferred Reporting Items for Systematic Reviews
and Meta-Analyses Statement was followed. Seven databases were searched for
published peer-reviewed articles. The incidence of HIV and syphilis in FSWs in
different time periods, provinces and workplaces in China were separately pooled
by meta-analysis. Correlation analysis was conducted between HIV and syphilis
incidence and study time, respectively. RESULTS: After 1,662 articles were
screened, 190 published papers were included in the final analysis. Estimated HIV
prevalence was 0.284% (95% CI: 0.080-0.488%) in the period 2000-2002, 0.211% (95%
CI: 0.149-0.273%) in 2003-2005, 0.242% (95% CI: 0.190-0.294%) in 2006-2008 and
0.041% (95% CI: 0.024-0.058%) in 2009-2011. The corresponding syphilis prevalence
was 9.669% (95% CI: 7.810-11.529%), 4.970% (95% CI: 4.384-5.556%), 4.404% (95%
CI: 4.032-4.775%) and 3.169% (95% CI: 2.738-3.600%), respectively. Spearman rank
correlation coefficients were -0.165 (p = 0.002) between HIV prevalence and study
time, and -0.209 (p = 0.000) between syphilis prevalence and study time. The
combined HIV prevalence was 0.318% (95% CI: 0.156-0.479%) in medium and high-tier
workplaces and 0.393% (95% CI: 0.176-0.610%) in low-tier workplaces. The
corresponding syphilis prevalence was 3.216% (95% CI: 2.192-4.240%) and 13.817%
(95% CI: 10.589-17.044%), respectively. CONCLUSIONS: Our data suggested a decline
in HIV and syphilis epidemics in FSWs in China on a national level during the
study period (2000-2011). FSWs in low-tier workplaces should be given more
attention in the future to ensure they are included in prevention programs for
HIV and sexually transmitted diseases.
PMID- 24349290
TI - Multiple transport-active binding sites are available for a single substrate on
human P-glycoprotein (ABCB1).
AB - P-glycoprotein (Pgp, ABCB1) is an ATP-Binding Cassette (ABC) transporter that is
associated with the development of multidrug resistance in cancer cells. Pgp
transports a variety of chemically dissimilar amphipathic compounds using the
energy from ATP hydrolysis. In the present study, to elucidate the binding sites
on Pgp for substrates and modulators, we employed site-directed mutagenesis, cell
and membrane-based assays, molecular modeling and docking. We generated single,
double and triple mutants with substitutions of the Y307, F343, Q725, F728, F978
and V982 residues at the proposed drug-binding site with cys in a cysless Pgp,
and expressed them in insect and mammalian cells using a baculovirus expression
system. All the mutant proteins were expressed at the cell surface to the same
extent as the cysless wild-type Pgp. With substitution of three residues of the
pocket (Y307, Q725 and V982) with cysteine in a cysless Pgp, QZ59S-SSS,
cyclosporine A, tariquidar, valinomycin and FSBA lose the ability to inhibit the
labeling of Pgp with a transport substrate, [(125)I]-Iodoarylazidoprazosin,
indicating these drugs cannot bind at their primary binding sites. However, the
drugs can modulate the ATP hydrolysis of the mutant Pgps, demonstrating that they
bind at secondary sites. In addition, the transport of six fluorescent substrates
in HeLa cells expressing triple mutant (Y307C/Q725C/V982C) Pgp is also not
significantly altered, showing that substrates bound at secondary sites are still
transported. The homology modeling of human Pgp and substrate and modulator
docking studies support the biochemical and transport data. In aggregate, our
results demonstrate that a large flexible pocket in the Pgp transmembrane domains
is able to bind chemically diverse compounds. When residues of the primary drug
binding site are mutated, substrates and modulators bind to secondary sites on
the transporter and more than one transport-active binding site is available for
each substrate.
PMID- 24349289
TI - Reverse engineering the neuroblastoma regulatory network uncovers MAX as one of
the master regulators of tumor progression.
AB - Neuroblastoma is the most common extracranial tumor and a major cause of infant
cancer mortality worldwide. Despite its importance, little is known about its
molecular mechanisms. A striking feature of this tumor is its clinical
heterogeneity. Possible outcomes range from aggressive invasion to other tissues,
causing patient death, to spontaneous disease regression or differentiation into
benign ganglioneuromas. Several efforts have been made in order to find tumor
progression markers. In this work, we have reconstructed the neuroblastoma
regulatory network using an information-theoretic approach in order to find genes
involved in tumor progression and that could be used as outcome predictors or as
therapeutic targets. We have queried the reconstructed neuroblastoma regulatory
network using an aggressive neuroblastoma metastasis gene signature in order to
find its master regulators (MRs). MRs expression profiles were then investigated
in other neuroblastoma datasets so as to detect possible clinical significance.
Our analysis pointed MAX as one of the MRs of neuroblastoma progression. We have
found that higher MAX expression correlated with favorable patient outcomes. We
have also found that MAX expression and protein levels were increased during
neuroblastoma SH-SY5Y cells differentiation. We propose that MAX is involved in
neuroblastoma progression, possibly increasing cell differentiation by means of
regulating the availability of MYC:MAX heterodimers. This mechanism is consistent
with the results found in our SH-SY5Y differentiation protocol, suggesting that
MAX has a more central role in these cells differentiation than previously
reported. Overexpression of MAX has been identified as anti-tumorigenic in other
works, but, to our knowledge, this is the first time that the link between the
expression of this gene and malignancy was verified under physiological
conditions.
PMID- 24349291
TI - Back from the brink: the Holocene history of the Carpathian barbel Barbus
carpathicus.
AB - As a result of specific adaptations and habitat preferences strongly rheophilic
fish species may show high levels of endemism. Many temperate rheophilic fish
species were subjected to a series of range contractions during the Pleistocene,
and then successfully expanded during the Holocene, colonising previously
abandoned areas. The Carpathian barbel (Barbus carpathicus Kotlik, Tsigenopoulos,
Rab et Berrebi 2002) occurs in the montane streams in three basins of the main
Central European rivers in the northern part of the Carpathian range. We used
genetic variation within 3 mitochondrial and 9 microsatellite loci to determine a
pattern of postglacial expansion in B. carpathicus. We found that overall genetic
variation within the species is relatively low. Estimate of time to the most
recent common ancestor (tMRCA) of mitochondrial sequences falls within the
Holocene. The highest levels of genetic variation found in upper reaches of the
Tisa river in the Danube basin suggest that glacial refugia were located in the
south-eastern part of the species range. Our data suggest that the species
crossed different watersheds at least six times as three genetically distinct
groups (probably established in different expansion episodes) were found in
northern part of the species range. Clines of genetic variation were observed in
both the Danube and Vistula basins, which probably resulted from subsequent
bottlenecks while colonizing successive habitats (south eastern populations) or
due to the admixture of genetically diverse individuals to a previously uniform
population (Vistula basin). Therefore, B. carpathicus underwent both demographic
breakdowns and expansions during the Holocene, showing its distribution and
demography are sensitive to environmental change. Our findings are important in
the light of the current human-induced habitats alterations.
PMID- 24349292
TI - The A930G polymorphism ofP22phox (CYBA) gene but not C242T variation is
associated with hypertension: a meta-analysis.
AB - BACKGROUND: Recently, it has been reported that the A930G and C242T polymorphisms
within p22phox (CYBA) gene are involved in the pathogenesis of hypertension.
However, the results remain controversial. Furthermore, no previous meta-analysis
has been conducted to evaluate the relationship between the A930G and C242T
polymorphisms and hypertension. Therefore, we performed this meta-analysis to
clarify these controversies. OBJECTIVE AND METHODS: All of the included articles
were retrieved from the PubMed and Embase databases, as well as the CNKI, CBM,
Chongqing VIP and Wan Fang databases according to the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR)
with corresponding 95% confidence intervals (CI) were used to assess the strength
of the association. Accounting for heterogeneity, a fixed or random effects model
was respectively adopted. Heterogeneity was checked using the Q test and the I(2)
statistic. A cumulative meta-analysis was conducted to estimate the tendency of
pooled OR. Funnel plots and Egger's tests were performed to test for possible
publication bias. RESULTS: Five articles on A930G with 2003 cases/2434 controls
and eight articles on C242T with 2644 cases/1967 controls were identified. A
significant association of A930G polymorphisms with the risk of hypertension was
found in the dominant model (OR=0.59, 95% CI: 0.38-0.92, p=0.021) and allelic
model (OR=0.66, 95% CI: 0.46-0.95, p=0.024). In the stratified analysis, a
significant association could be found among the hospital-based and population
based studies. However, no evidence of a significant association of the C242T
polymorphism with hypertension was found in the overall analysis and subgroup
analysis. CONCLUSIONS: This meta-analysis indicates that the A930G polymorphism,
but not the C242T variation, might be a protective factor for hypertension.
PMID- 24349293
TI - The effectiveness of acupuncture in prevention and treatment of postoperative
nausea and vomiting--a systematic review and meta-analysis.
AB - BACKGROUND: Acupuncture therapy for preventive and treatment of postoperative
nausea and vomiting(PONV), a condition which commonly present after anaesthesia
and surgery is a subject of growing interest. OBJECTIVE: This paper included a
systematic review and meta-analysis on the effect of different type of
acupuncture and acupoint selection in PONV prevention and treatment. METHODS:
Randomised controlled trials(RCTs) comparing acupuncture with non-acupuncture
treatment were identified from databases PubMed, Cochrane, EBSCO, Ovid, CNKI and
Wanfangdata. Meta-analysis on eligible studies was performed using fixed-effects
model with RevMan 5.2. Results were expressed as RR for dichotomous data, with
95%CI. RESULTS: Thirty RCTs, 1276 patients (intervention) and 1258 patients
(control) were identified. Meta-analysis showed that PC6 acupuncture
significantly reduced the number of cases of early vomiting (postoperative 0-6h)
(RR=0.36, 95%CI 0.19,0.71; P=0.003) and nausea (postoperative 0-24h) (RR=0.25,
95%CI 0.10,0.61; P=0.002), but not early nausea (postoperative 0-6h) (RR=0.64,
95%CI 0.34,1.19; P=0.150) and vomiting (postoperative 0-24h) (RR=0.82, 95%CI
0.48,1.38; P=0.450). PC6 acupressure significantly reduced the number of cases of
nausea (RR=0.71, 95%CI 0.57,0.87; P=0.001) and vomiting (RR=0.62, 95%CI
0.49,0.80; P=0.000) at postoperative 0-24h. PC6 electro-acupoint stimulation
significantly reduced the number of cases of nausea (RR=0.49, 95%CI 0.38,0.63;
P<0.000) and vomiting (RR=0.50, 95%CI 0.36,0.70; P<0.000) at postoperative 0-24h.
Stimulation of PC6 with other acupoint(s) significantly reduced the number of
cases of nausea and vomiting (RR=0.29, 95%CI 0.17,0.49; P<0.000) at postoperative
0-24h. Stimulation of other acupoint(s)(non PC6) also significantly reduced the
number of cases of nausea and vomiting (RR=0.63, 95%CI 0.49,0.81; P=0.000) at
postoperative 0-24h. However, the quality of study was generally low in studies
of PC6 combined with other acupoint(s) and other acupoint(s). Details of blinding
were not reported in most reports. CONCLUSIONS: Besides PC6, PC6 combined with
other acupoint(s) and other alternative acupoint(s) might be beneficial in
prevention and treatment of PONV, the evidence justifies future high-quality
studies.
PMID- 24349295
TI - Modelling size-dependent cannibalism in barramundi Lates calcarifer:
cannibalistic polyphenism and its implication to aquaculture.
AB - This study quantified size-dependent cannibalism in barramundi Lates calcarifer
through coupling a range of prey-predator pairs in a different range of fish
sizes. Predictive models were developed using morphological traits with the
alterative assumption of cannibalistic polyphenism. Predictive models were
validated with the data from trials where cannibals were challenged with
progressing increments of prey sizes. The experimental observations showed that
cannibals of 25-131 mm total length could ingest the conspecific prey of 78-72%
cannibal length. In the validation test, all predictive models underestimate the
maximum ingestible prey size for cannibals of a similar size range. However, the
model based on the maximal mouth width at opening closely matched the empirical
observations, suggesting a certain degree of phenotypic plasticity of mouth size
among cannibalistic individuals. Mouth size showed allometric growth comparing
with body depth, resulting in a decreasing trend on the maximum size of
ingestible prey as cannibals grow larger, which in parts explains why cannibalism
in barramundi is frequently observed in the early developmental stage. Any
barramundi has the potential to become a cannibal when the initial prey size was
<50% of the cannibal body length, but fish could never become a cannibal when
prey were >58% of their size, suggesting that 50% of size difference can be the
threshold to initiate intracohort cannibalism in a barramundi population.
Cannibalistic polyphenism was likely to occur in barramundi that had a
cannibalistic history. An experienced cannibal would have a greater ability to
stretch its mouth size to capture a much larger prey than the models predict. The
awareness of cannibalistic polyphenism has important application in fish farming
management to reduce cannibalism.
PMID- 24349294
TI - Mortality among methadone maintenance clients in China: a six-year cohort study.
AB - OBJECTIVE: To assess the overall mortality of methadone maintenance treatment
(MMT) clients in China and its associated factors. METHODS: A total of 1,511 MMT
clients, all of whom enrolled in China's first eight MMT clinics between March
and December 2004, were included in this cohort study and followed for
approximately six years, until June 2010. Mortality and its predictors were
examined using Cox proportional hazards regression models. RESULTS: A total of
154 deaths were observed within 5,391 person-years (PY) of follow-up for an all
cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug
overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The
all-cause mortality rate of clients engaged in MMT for one year or less was
roughly three times that of clients who stayed in MMT for four years or more
(14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality
rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV
positive subjects had approximately two times higher mortality rate than those
receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding
variables, we found that being male (HR = 1.63, CI: 1.03-2.57, p = 0.0355) and
being HIV-positive (HR = 5.16, CI: 3.70-7.10, p<0.0001) were both associated with
higher risk of death whereas increased durations of methadone treatment were
associated with a lower risk of death (HR = 0.26, CI: 0.18-0.38, p<0.0001 for two
to three years, HR = 0.08, CI: 0.05-0.14, p<0.0001 for four or more years).
CONCLUSION: Overall mortality was high among MMT clients in China. Specific
interventions aimed at decreasing mortality among MMT clients are needed. Our
study supports the need for keeping client at MMT longer and for expanding ART
coverage and suggests the potential benefits of integrated MMT and ART services
for drug users in China.
PMID- 24349296
TI - Identifying biologically meaningful hot-weather events using threshold
temperatures that affect life-history.
AB - Increases in the frequency, duration and intensity of heat waves are frequently
evoked in climate change predictions. However, there is no universal definition
of a heat wave. Recent, intense hot weather events have caused mass mortalities
of birds, bats and even humans, making the definition and prediction of heat wave
events that have the potential to impact populations of different species an
urgent priority. One possible technique for defining biologically meaningful heat
waves is to use threshold temperatures (T(thresh)) above which known fitness
costs are incurred by species of interest. We set out to test the utility of this
technique using T(thresh) values that, when exceeded, affect aspects of the
fitness of two focal southern African bird species: the southern pied babbler
Turdiodes bicolor (T(thresh) = 35.5 degrees C) and the common fiscal Lanius
collaris (T(thresh) = 33 degrees C). We used these T(thresh) values to analyse
trends in the frequency, duration and intensity of heat waves of magnitude
relevant to the focal species, as well as the annual number of hot days (maximum
air temperature > T(thresh)), in north-western South Africa between 1961 and
2010. Using this technique, we were able to show that, while all heat wave
indices increased during the study period, most rapid increases for both species
were in the annual number of hot days and in the maximum intensity (and therefore
intensity variance) of biologically meaningful heat waves. Importantly, we also
showed that warming trends were not uniform across the study area and that
geographical patterns in warming allowed both areas of high risk and potential
climate refugia to be identified. We discuss the implications of the trends we
found for our focal species, and the utility of the T(thresh) technique as a
conservation tool.
PMID- 24349297
TI - Molecular evolution and diversity of Conus peptide toxins, as revealed by gene
structure and intron sequence analyses.
AB - Cone snails, which are predatory marine gastropods, produce a cocktail of venoms
used for predation, defense and competition. The major venom component,
conotoxin, has received significant attention because it is useful in
neuroscience research, drug development and molecular diversity studies. In this
study, we report the genomic characterization of nine conotoxin gene
superfamilies from 18 Conus species and investigate the relationships among
conotoxin gene structure, molecular evolution and diversity. The I1, I2, M, O2,
O3, P, S, and T superfamily precursors all contain three exons and two introns,
while A superfamily members contain two exons and one intron. The introns are
conserved within a certain gene superfamily, and also conserved across different
Conus species, but divergent among different superfamilies. The intronic
sequences contain many simple repeat sequences and regulatory elements that may
influence conotoxin gene expression. Furthermore, due to the unique gene
structure of conotoxins, the base substitution rates and the number of positively
selected sites vary greatly among exons. Many more point mutations and
trinucleotide indels were observed in the mature peptide exon than in the other
exons. In addition, the first example of alternative splicing in conotoxin genes
was found. These results suggest that the diversity of conotoxin genes has been
shaped by point mutations and indels, as well as rare gene recombination or
alternative splicing events, and that the unique gene structures could have made
a contribution to the evolution of conotoxin genes.
PMID- 24349298
TI - Enhanced responses to tumor immunization following total body irradiation are
time-dependent.
AB - The development of successful cancer vaccines is contingent on the ability to
induce effective and persistent anti-tumor immunity against self-antigens that do
not typically elicit immune responses. In this study, we examine the effects of a
non-myeloablative dose of total body irradiation on the ability of tumor-naive
mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation
followed by lymphocyte infusion results in a dramatic increase in responsiveness
to tumor vaccination, with augmentation of T cell responses to tumor antigens and
tumor eradication. In irradiated mice, infused CD8(+) T cells expand in an
environment that is relatively depleted in regulatory T cells, and this
correlates with improved CD8(+) T cell functionality. We also observe an increase
in the frequency of dendritic cells displaying an activated phenotype within
lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the
relative decrease in regulatory T cells and increase in activated dendritic cells
correspond with a brief window of augmented responsiveness to immunization. After
this 24 hour window, the numbers of dendritic cells decline, as does the ability
of mice to respond to immunizations. When immunizations are initiated within the
period of augmented dendritic cell activation, mice develop anti-tumor responses
that show increased durability as well as magnitude, and this approach leads to
improved survival in experiments with mice bearing established tumors as well as
in a spontaneous melanoma model. We conclude that irradiation can produce potent
immune adjuvant effects independent of its ability to induce tumor ablation, and
that the timing of immunization and lymphocyte infusion in the irradiated host
are crucial for generating optimal anti-tumor immunity. Clinical strategies using
these approaches must therefore optimize such parameters, as the correct timing
of infusion and vaccination may mean the difference between an ineffective
treatment and successful tumor eradication.
PMID- 24349299
TI - Inhibitory effects of vinpocetine on the progression of atherosclerosis are
mediated by Akt/NF-kappaB dependent mechanisms in apoE-/- mice.
AB - BACKGROUND: Recent studies have found additional roles for vinpocetine, a potent
phosphodiesterase type I inhibitor, in anti-proliferation and anti-inflammation
of vascular smooth muscle cells and cancer cells via different mechanisms. In
this study, we attempted to investigate whether vinpocetine protected against
atherosclerotic development in apoE(-/-) mice and explore the underlying anti
atherogenic mechanisms in macrophages. METHODOLOGY/PRINCIPAL FINDINGS:
Vinpocetine markedly decreased atherosclerotic lesion size in apoE(-/-) mice
measured by oil red O. Masson's trichrome staining and immunohistochemical
analyses revealed that vinpocetine significantly increased the thickness of
fibrous cap, reduced the size of lipid-rich necrotic core and attenuated
inflammation. In vitro experiments exhibited a significant decrease in monocyte
adhesion treated with vinpocetine. Further, active TNF-alpha, IL-6, monocyte
chemoattractant protein-1 and matrix metalloproteinase-9 expression induced by ox
LDL were attenuated by vinpocetine in a dose-dependent manner. Similarly, ox-LDL
induced reactive oxygen species were significantly repressed by vinpocetine. Both
western blot and luciferase activity assay showed that vinpocetine inhibited the
enhanced Akt, IKKalpha/beta, IkappaBalpha phosphorylation and NF-kappaB activity
induced by ox-LDL, and the inhibition of NF-kappaB activity was partly caused by
Akt dephosphorylation. However, knockdown of PDE1B did not affect Akt,
IKKalpha/beta and IkappaBalpha phosphorylation. CONCLUSIONS: These results
suggest that vinpocetine exerts anti-atherogenic effects through inhibition of
monocyte adhesion, oxidative stress and inflammatory response, which are mediated
by Akt/NF-kappaB dependent pathway but independent of PDE1 blockade in
macrophages.
PMID- 24349300
TI - Population genetic structure of a microalgal species under expansion.
AB - Biological invasions often cause major perturbations in the environment and are
well studied among macroorganisms. Less is known about invasion by free-living
microbes. Gonyostomum semen (Raphidophyceae) is a freshwater phytoplankton
species that has increased in abundance in Northern Europe since the 1980's and
has expanded its habitat range. In this study, we aimed to determine the genetic
population structure of G. semen in Northern Europe and to what extent it
reflects the species' recent expansion. We sampled lakes from 12 locations (11
lakes) in Norway, Sweden and Finland. Multiple strains from each location were
genotyped using Amplified Fragment Length Polymorphism (AFLP). We found low
differentiation between locations, and low gene diversity within each location.
Moreover, there was an absence of genetic isolation with distance (Mantel test, p
= 0.50). According to a Bayesian clustering method all the isolates belonged to
the same genetic population. Together our data suggest the presence of one
metapopulation and an overall low diversity, which is coherent with a recent
expansion of G. semen.
PMID- 24349301
TI - Quantitative phosphoproteomic analysis identifies activation of the RET and IGF
1R/IR signaling pathways in neuroblastoma.
AB - Neuroblastoma is an embryonal tumor of childhood with a heterogenous clinical
presentation that reflects differences in activation of complex biological
signaling pathways. Protein phosphorylation is a key component of cellular signal
transduction and plays a critical role in processes that control cancer cell
growth and survival. We used shotgun LC/MS to compare phosphorylation between a
human MYCN amplified neuroblastoma cell line (NB10), modeling a resistant tumor,
and a human neural precursor cell line (NPC), modeling a normal baseline neural
crest cell. 2181 unique phosphorylation sites representing 1171 proteins and 2598
phosphopeptides were found. Protein kinases accounted for 6% of the proteome,
with a predominance of tyrosine kinases, supporting their prominent role in
oncogenic signaling pathways. Highly abundant receptor tyrosine kinase (RTK)
phosphopeptides in the NB10 cell line relative to the NPC cell line included RET,
insulin-like growth factor 1 receptor/insulin receptor (IGF-1R/IR), and
fibroblast growth factor receptor 1 (FGFR1). Multiple phosphorylated peptides
from downstream mediators of the PI3K/AKT/mTOR and RAS pathways were also highly
abundant in NB10 relative to NPC. Our analysis highlights the importance of RET,
IGF-1R/IR and FGFR1 as RTKs in neuroblastoma and suggests a methodology that can
be used to identify potential novel biological therapeutic targets. Furthermore,
application of this previously unexploited technology in the clinic opens the
possibility of providing a new wide-scale molecular signature to assess disease
progression and prognosis.
PMID- 24349302
TI - Quorum sensing and self-quorum quenching in the intracellular pathogen
Brucellamelitensis.
AB - Brucella quorum sensing has been described as an important regulatory system
controlling crucial virulence determinants such as the VirB type IV secretion
system and the flagellar genes. However, the basis of quorum sensing, namely the
production of autoinducers in Brucella has been questioned. Here, we report data
obtained from the use of a genetic tool allowing the in situ detection of long
chain N-acyl-homoserine lactones (AHL) activity at single bacterium level in
Brucella melitensis. These data are consistent with an intrinsic production of
AHL by B. melitensis in low concentration both during in vitro growth and
macrophage infection. Moreover, we identified a protein, named AibP, which is
homologous to the AHL-acylases of various bacterial species. In vitro and during
infection, expression of aibP coincided with a decrease in endogenous AHL
activity within B. melitensis, suggesting that AibP could efficiently impair AHL
accumulation. Furthermore, we showed that deletion of aibP in B. melitensis
resulted in enhanced virB genes expression and VirB8 production as well as in a
reduced flagellar genes expression and production of FlgE (hook protein) and FliC
(flagellin) in vitro. Altogether, these results suggest that AHL-dependent quorum
sensing and AHL-quorum quenching coexist in Brucella, at least to regulate its
virulence.
PMID- 24349303
TI - Molecular epidemiology of nontypeable Haemophilus influenzae causing community
acquired pneumonia in adults.
AB - Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen which
causes a variety of respiratory infections. The objectives of the study were to
determine its antimicrobial susceptibility, to characterize the beta-lactam
resistance, and to establish a genetic characterization of NTHi isolates. Ninety
five NTHi isolates were analyzed by pulsed field gel electrophoresis (PFGE) and
multi locus sequence typing (MLST). Antimicrobial susceptibility was determined
by microdilution, and the ftsI gene (encoding penicillin-binding protein 3, PBP3)
was PCR amplified and sequenced. Thirty (31.6%) isolates were non-susceptible to
ampicillin (MIC >= 2 mg/L), with 10 of them producing beta-lactamase type TEM-1
as a resistance mechanism. After ftsI sequencing, 39 (41.1%) isolates showed
amino acid substitutions in PBP3, with Asn526 -> Lys being the most common
(69.2%). Eighty-four patients were successfully treated with
amoxicillin/clavulanic acid, ceftriaxone and levofloxacin. Eight patients died
due either to aspiration or complication of their comorbidities. In conclusion,
NTHi causing CAP in adults shows high genetic diversity and is associated with a
high rate of reduced susceptibility to ampicillin due to alterations in PBP3. The
analysis of treatment and outcomes demonstrated that NTHi strains with mutations
in the ftsI gene could be successfully treated with ceftriaxone or
fluoroquinolones.
PMID- 24349304
TI - Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a
systematic review and meta-analysis.
AB - Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important
role in the inflammatory and immunologic response. Numerous studies have shown
LTA polymorphisms as risk factors for cancers, but the results remain
inconclusive. The goal of the present meta-analyses is to establish the
associations between cancers and four LTA variants (rs1041981, rs2239704,
rs2229094 and rs746868). A total of 30 case-control studies involving 58,649
participants were included in the current meta-analyses. Our results showed
significant associations with increased cancer risk for rs1041981 (odd ratio (OR)
= 1.15, 99% confidential interval (CI) = 1.07-1.25, P < 0.0001, I(2) = 12.2%),
rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I(2) = 0.0%) and rs2229094
(OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I(2) = 0.0%). No evidence was found
for the association between rs746868 and cancer risk (OR = 1.01, 99% CI = 0.93
1.10, P = 0.771, I(2) = 0.0%). Subgroup meta-analysis suggested that rs2239704
was likely to increase the risk of hematological malignancy (OR = 1.10, 99% CI =
1.01-1.20, P = 0.023, I(2) = 0.0%), and rs2229094 was specific for the increased
risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I(2) = 0.0%).
In conclusion, our meta-analyses suggested that the LTA rs1041981, rs2239704 and
rs2229094 polymorphisms contributed to the increased risk of cancers. Future
functional studies were needed to clarify the mechanistic roles of the three
variants in the cancer risk.
PMID- 24349305
TI - Strain-independent increases of crystallin proteins in the retina of type 1
diabetic rats.
AB - Diabetic retinopathy is the leading cause of vision loss in working-age
individuals in the United States and is expected to continue growing with the
increased prevalence of diabetes. Streptozotocin-induced hyperglycemia in rats is
the most commonly used model for diabetic retinopathy. Previous studies have
shown that this model can lead to different inflammatory changes in the retina
depending on the strain of rat. Our previous work has shown that crystallin
proteins, including members of the alpha- and beta/gamma-crystallin subfamilies,
are upregulated in the STZ rat retina. Crystallin proteins have been implicated
in a number of cellular processes, such as neuroprotection, non-native protein
folding and vascular remodeling. In this current study, we have demonstrated that
unlike other strain-dependent changes, such as inflammatory cytokines and growth
factor levels, in the STZ rat, the protein upregulation of crystallins is
consistent across the Brown Norway, Long-Evans and Sprague-Dawley rat strains in
the context of diabetes. Taken together, these data illustrate the potential
critical role played by crystallins, and especially alpha-crystallins, in the
retina in the context of diabetes.
PMID- 24349306
TI - Interleukin-encoding adenoviral vectors as genetic adjuvant for vaccination
against retroviral infection.
AB - Interleukins (IL) are cytokines with stimulatory and modulatory functions in the
immune system. In this study, we have chosen interleukins which are involved in
the enhancement of TH2 responses and B cell functions to analyze their potential
to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to
antibody and virus-specific CD4(+) T cell responses. Mice were vaccinated with an
adenoviral vector which encodes and displays the Friend Virus (FV) surface
envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors
encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of
Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with
high control over FV-induced splenomegaly and reduced viral loads. Mice co
immunized with adenoviral vectors encoding IL5 or IL23 showed increased
neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23
showed improved FV-specific CD4(+) T cell responses compared to mice immunized
with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors
encoding specific interleukins is suitable to improve the vaccination efficacy of
an anti-retroviral vaccine. Improved protection correlated with improved CD4(+) T
cell responses and especially with higher neutralizing antibody titers. The co
application of selected interleukin-encoding adenoviral vectors is a valuable
tool for vaccination with regard to enhancement of antibody mediated immunity.
PMID- 24349307
TI - Reconstitution of cholesterol-dependent vaginolysin into tethered phospholipid
bilayers: implications for bioanalysis.
AB - Functional reconstitution of the cholesterol-dependent cytolysin vaginolysin
(VLY) from Gardnerella vaginalis into artificial tethered bilayer membranes
(tBLMs) has been accomplished. The reconstitution of VLY was followed in real
time by electrochemical impedance spectroscopy (EIS). Changes of the EIS
parameters of the tBLMs upon exposure to VLY solutions were consistent with the
formation of water-filled pores in the membranes. It was found that
reconstitution of VLY is a strictly cholesterol-dependent, irreversible process.
At a constant cholesterol concentration reconstitution of VLY occurred in a
concentration-dependent manner, thus allowing the monitoring of VLY concentration
and activity in vitro and opening possibilities for tBLM utilization in
bioanalysis. EIS methodology allowed us to detect VLY down to 0.5 nM (28 ng/mL)
concentration. Inactivation of VLY by certain amino acid substitutions led to
noticeably lesser tBLM damage. Pre-incubation of VLY with the neutralizing
monoclonal antibody 9B4 inactivated the VLY membrane damage in a concentration
dependent manner, while the non-neutralizing antibody 21A5 exhibited no effect.
These findings demonstrate the biological relevance of the interaction between
VLY and the tBLM. The membrane-damaging interaction between VLY and tBLM was
observed in the absence of the human CD59 receptor, known to strongly facilitate
the hemolytic activity of VLY. Taken together, our study demonstrates the
applicability of tBLMs as a bioanalytical platform for the detection of the
activity of VLY and possibly other cholesterol-dependent cytolysins.
PMID- 24349308
TI - TALE-PvuII fusion proteins--novel tools for gene targeting.
AB - Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and
the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA
cleavage module. This architecture is also used by TALE nucleases (TALENs), in
which the DNA-binding modules of the ZFNs have been replaced by DNA-binding
domains based on transcription activator like effector (TALE) proteins. Both
TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI
to induce double-strand DNA cleavage at the target site after recognition of the
target DNA by the respective DNA-binding module. TALENs seem to have an advantage
over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we
present evidence that variant TALENs can be produced by replacing the catalytic
domain of FokI with the restriction endonuclease PvuII. These fusion proteins
recognize only the composite recognition site consisting of the target site of
the TALE protein and the PvuII recognition sequence (addressed site), but not
isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess
of protein over DNA and long incubation times. In vitro, their preference for an
addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion
proteins are active in cellula with minimal cytotoxicity.
PMID- 24349309
TI - Exposure to atmospheric particulate matter enhances Th17 polarization through the
aryl hydrocarbon receptor.
AB - Lung diseases, including asthma, COPD, and other autoimmune lung pathologies are
aggravated by exposure to particulate matter (PM) found in air pollution. IL-17
has been shown to exacerbate airway disease in animal models. As PM is known to
contain aryl hydrocarbon receptor (AHR) ligands and the AHR has recently been
shown to play a role in differentiation of Th17 T cells, the aim of this study
was to determine whether exposure to PM could impact Th17 polarization in an AHR
dependent manner. This study used both cell culture techniques and in vivo
exposure in mice to examine the response of T cells to PM. Initially experiments
were conducted with urban dust particles from a standard reference material, and
ultimately repeated with freshly collected samples of diesel exhaust and
cigarette smoke. The readout for the assays was increased T cell differentiation
as indicated by increased generation of IL-17A in culture, and increased
populations of IL-17 producing cells by intracellular flow cytometry. The data
illustrate that Th17 polarization was significantly enhanced by addition of urban
dust in a dose dependent fashion in cultures of wild-type but not AHR(-/-) mice.
The data further suggest that polycyclic aromatic hydrocarbons played a primary
role in this enhancement. There was both an increase of Th17 cell
differentiation, and also an increase in the amount of IL-17 secreted by the
cells. In summary, this paper identifies a novel mechanism whereby PM can
directly act on the AHR in T cells, leading to enhanced Th17 differentiation.
Further understanding of the molecular mechanisms responsible for pathologic Th17
differentiation and autoimmunity seen after exposure to pollution will allow
direct targeting of proteins involved in AHR activation and function for
treatment of PM exposures.
PMID- 24349310
TI - CLCN1 mutations in Czech patients with myotonia congenita, in silico analysis of
novel and known mutations in the human dimeric skeletal muscle chloride channel.
AB - Myotonia congenita (MC) is a genetic disease caused by mutations in the skeletal
muscle chloride channel gene (CLCN1) encoding the skeletal muscle chloride
channel (ClC-1). Mutations of CLCN1 result in either autosomal dominant MC
(Thomsen disease) or autosomal recessive MC (Becker disease). The ClC-1 protein
is a homodimer with a separate ion pore within each monomer. Mutations causing
recessive myotonia most likely affect properties of only the mutant monomer in
the heterodimer, leaving the wild type monomer unaffected, while mutations
causing dominant myotonia affect properties of both subunits in the heterodimer.
Our study addresses two points: 1) molecular genetic diagnostics of MC by
analysis of the CLCN1 gene and 2) structural analysis of mutations in the
homology model of the human dimeric ClC-1 protein. In the first part, 34
different types of CLCN1 mutations were identified in 51 MC probands (14
mutations were new). In the second part, on the basis of the homology model we
identified the amino acids which forming the dimer interface and those which form
the Cl(-) ion pathway. In the literature, we searched for mutations of these
amino acids for which functional analyses were performed to assess the
correlation between localisation of a mutation and occurrence of a dominant
negative effect (corresponding to dominant MC). This revealed that both types of
mutations, with and without a dominant-negative effect, are localised at the
dimer interface while solely mutations without a dominant-negative effect occur
inside the chloride channel. This work is complemented by structural analysis of
the homology model which provides elucidation of the effects of mutations,
including a description of impacts of newly detected missense mutations.
PMID- 24349311
TI - Is fluid overload more important than diabetes in renal progression in late
chronic kidney disease?
AB - Fluid overload is one of the major presentations in patients with late stage
chronic kidney disease (CKD). Diabetes is the leading cause of renal failure, and
progression of diabetic nephropathy has been associated with changes in
extracellular fluid volume. The aim of the study was to assess the association of
fluid overload and diabetes in commencing dialysis and rapid renal function
decline (the slope of estimated glomerular filtration rate (eGFR) less than -3
ml/min per 1.73 m(2)/y) in 472 patients with stages 4-5 CKD. Fluid status was
determined by bioimpedance spectroscopy method, Body Composition Monitor. The
study population was further classified into four groups according to the median
of relative hydration status (?HS =fluid overload/extracellular water) and the
presence or absence of diabetes. The median level of relative hydration status
was 7%. Among all patients, 207(43.9 %) were diabetic. 71 (15.0%) subjects had
commencing dialysis, and 187 (39.6%) subjects presented rapid renal function
decline during a median 17.3-month follow-up. Patients with fluid overload had a
significantly increased risk for commencing dialysis and renal function decline
independent of the presence or absence of diabetes. No significantly increased
risk for renal progression was found between diabetes and non-diabetes in late
CKD without fluid overload. In conclusion, fluid overload has a higher predictive
value of an elevated risk for renal progression than diabetes in late CKD.
PMID- 24349312
TI - C-terminus of the B-chain of relaxin-3 is important for receptor activity.
AB - Human relaxin-3 is a neuropeptide that is structurally similar to human insulin
with two chains (A and B) connected by three disulfide bonds. It is expressed
primarily in the brain and has modulatory roles in stress and anxiety, feeding
and metabolism, and arousal and behavioural activation. Structure-activity
relationship studies have shown that relaxin-3 interacts with its cognate
receptor RXFP3 primarily through its B-chain and that its A-chain does not have
any functional role. In this study, we have investigated the effect of
modification of the B-chain C-terminus on the binding and activity of the
peptide. We have chemically synthesised and characterized H3 relaxin as C-termini
acid (both A and B chains having free C-termini; native form) and amide forms
(both chains' C-termini were amidated). We have confirmed that the acid form of
the peptide is more potent than its amide form at both RXFP3 and RXFP4 receptors.
We further investigated the effects of amidation at the C-terminus of individual
chains. We report here for the first time that amidation at the C-terminus of the
B-chain of H3 relaxin leads to significant drop in the binding and activity of
the peptide at RXFP3/RXFP4 receptors. However, modification of the A-chain C
terminus does not have any effect on the activity. We have confirmed using
circular dichroism spectroscopy that there is no secondary structural change
between the acid and amide form of the peptide, and it is likely that it is the
local C-terminal carboxyl group orientation that is crucial for interacting with
the receptors.
PMID- 24349313
TI - Should physical activity recommendations be ethnicity-specific? Evidence from a
cross-sectional study of South Asian and European men.
AB - BACKGROUND: Expert bodies and health organisations recommend that adults
undertake at least 150 min.week(-1) of moderate-intensity physical activity
(MPA). However, the underpinning data largely emanate from studies of populations
of European descent. It is unclear whether this level of activity is appropriate
for other ethnic groups, particularly South Asians, who have increased cardio
metabolic disease risk compared to Europeans. The aim of this study was to
explore the level of MPA required in South Asians to confer a similar cardio
metabolic risk profile to that observed in Europeans undertaking the currently
recommended MPA level of 150 min.week(-1). METHODS: Seventy-five South Asian and
83 European men, aged 40-70, without cardiovascular disease or diabetes had
fasted blood taken, blood pressure measured, physical activity assessed
objectively (using accelerometry), and anthropometric measures made. Factor
analysis was used to summarise measured risk biomarkers into underlying latent
'factors' for glycaemia, insulin resistance, lipid metabolism, blood pressure,
and overall cardio-metabolic risk. Age-adjusted regression models were used to
determine the equivalent level of MPA (in bouts of >= 10 minutes) in South Asians
needed to elicit the same value in each factor as Europeans undertaking 150
min.week(-1) MPA. FINDINGS: For all factors, except blood pressure, equivalent
MPA values in South Asians were significantly higher than 150 min.week(-1); the
equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI
185-347) min.week(-1). CONCLUSIONS: South Asian men may need to undertake greater
levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile,
suggesting that a conceptual case can be made for ethnicity-specific physical
activity guidance. Further study is needed to extend these findings to women and
to replicate them prospectively in a larger cohort.
PMID- 24349314
TI - Cost-effectiveness analysis of breast cancer control interventions in Peru.
AB - OBJECTIVES: In Peru, a country with constrained health resources, breast cancer
control is characterized by late stage treatment and poor survival. To support
breast cancer control in Peru, this study aims to determine the cost
effectiveness of different breast cancer control interventions relevant for the
Peruvian context. METHODS: We performed a cost-effectiveness analysis (CEA)
according to WHO-CHOICE guidelines, from a healthcare perspective. Different
screening, early detection, palliative, and treatment interventions were
evaluated using mathematical modeling. Effectiveness estimates were based on
observational studies, modeling, and on information from Instituto Nacional de
Enfermedades Neoplasicas (INEN). Resource utilizations and unit costs were based
on estimates from INEN and observational studies. Cost-effectiveness estimates
are in 2012 United States dollars (US$) per disability adjusted life year (DALY)
averted. RESULTS: The current breast cancer program in Peru ($8,426 per DALY
averted) could be improved through implementing triennial or biennial screening
strategies. These strategies seem the most cost-effective in Peru, particularly
when mobile mammography is applied (from $4,125 per DALY averted), or when both
CBE screening and mammography screening are combined (from $4,239 per DALY
averted). Triennially, these interventions costs between $63 million and $72
million per year. Late stage treatment, trastuzumab therapy and annual screening
strategies are the least cost-effective. CONCLUSIONS: Our analysis suggests that
breast cancer control in Peru should be oriented towards early detection through
combining fixed and mobile mammography screening (age 45-69) triennially.
However, a phased introduction of triennial CBE screening (age 40-69) with
upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography
screening (age 50-69) in urban settings, seems a more feasible option and is also
cost-effective. The implementation of this intervention is only meaningful if
awareness raising, diagnostic, referral, treatment and basic palliative services
are simultaneously improved, and if financial and organizational barriers to
these services are reduced.
PMID- 24349315
TI - Design, synthesis of novel lipids as chemical permeation enhancers and
development of nanoparticle system for transdermal drug delivery.
AB - In the present study, we designed and developed novel lipids that include (Z)-1
(Octadec-9-en-1-yl)-pyrrolidine (Cy5T), 1, 1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin
1-ium iodide (Cy5), (Z)-1-(Octadec-9-en-1-yl)-piperidine (Cy6T), and 1, 1-Di-((Z)
octadec-9-en-1-yl) piperidin-1-ium iodide (Cy6) to enhance the transdermal
permeation of some selected drugs. Firstly, we evaluated the transdermal
permeation efficacies of these lipids as chemical permeation enhancers in vehicle
formulations for melatonin, beta-estradiol, caffeine, alpha-MSH, and spantide
using franz diffusion cells. Among them Cy5 lipid was determined to be the most
efficient by increasing the transdermal permeation of melatonin, beta-estradiol,
caffeine, alpha-MSH, and spantide by 1.5 to 3.26-fold more at the epidermal layer
and 1.3 to 2.5-fold more at the dermal layer, in comparison to either NMP or OA.
Hence we developed a nanoparticle system (cy5 lipid ethanol drug nanoparticles)
to evaluate any further improvement in the drug penetration. Cy5 lipid formed
uniformly sized nanoparticles ranging from 150-200 nm depending on the type of
drug. Further, Cy5 based nanoparticle system significantly (p<0.05) increased the
permeation of all the drugs in comparison to the lipid solution and standard
permeation enhancers. There were about 1.54 to 22-fold more of drug retained in
the dermis for the Cy5 based nanoparticles compared to OA/NMP standard enhancers
and 3.87 to 66.67-fold more than lipid solution. In addition, epifluorescent
microscopic analysis in rhodamine-PE permeation studies confirmed the superior
permeation enhancement of LEDs (detection of fluorescence up to skin depth of 340
MUm) more than lipid solution, which revealed fluorescence up to skin depth of
only 260 MUm. In summary the present findings demonstrate that i) cationic lipid
with 5 membered amine heterocyclic ring has higher permeating efficacy than the 6
membered amine hertocyclic ring. ii) The nanoparticle system prepared with Cy5
showed significant (p<0.05) increase in the permeation of the drugs than the
control penetration enhancers, oleic acid and NMP.
PMID- 24349316
TI - Human L-ficolin, a recognition molecule of the lectin activation pathway of
complement, activates complement by binding to pneumolysin, the major toxin of
Streptococcus pneumoniae.
AB - The complement system is an essential component of the immune response, providing
a critical line of defense against different pathogens including S. pneumoniae.
Complement is activated via three distinct pathways: the classical (CP), the
alternative (AP) and the lectin pathway (LP). The role of Pneumolysin (PLY), a
bacterial toxin released by S. pneumoniae, in triggering complement activation
has been studied in vitro. Our results demonstrate that in both human and mouse
sera complement was activated via the CP, initiated by direct binding of even non
specific IgM and IgG3 to PLY. Absence of CP activity in C1q(-/-) mouse serum
completely abolished any C3 deposition. However, C1q depleted human serum
strongly opsonized PLY through abundant deposition of C3 activation products,
indicating that the LP may have a vital role in activating the human complement
system on PLY. We identified that human L-ficolin is the critical LP recognition
molecule that drives LP activation on PLY, while all of the murine LP recognition
components fail to bind and activate complement on PLY. This work elucidates the
detailed interactions between PLY and complement and shows for the first time a
specific role of the LP in PLY-mediated complement activation in human serum.
PMID- 24349317
TI - Functional characterization of ECP-heparin interaction: a novel molecular model.
AB - Human eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN)
are two ribonuclease A (RNaseA) family members secreted by activated eosinophils.
They share conserved catalytic triad and similar three dimensional structures.
ECP and EDN are heparin binding proteins with diverse biological functions. We
predicted a novel molecular model for ECP binding of heparin hexasaccharide
(Hep6), [GlcNS(6S)-IdoA(2S)]3, and residues Gln(40), His(64) and Arg(105) were
indicated as major contributions for the interaction. Interestingly, Gln(40) and
His(64) on ECP formed a clamp-like structure to stabilize Hep6 in our model,
which was not observed in the corresponding residues on EDN. To validate our
prediction, mutant ECPs including ECP Q40A, H64A, R105A, and double mutant ECP
Q40A/H64A were generated, and their binding affinity for heparins were measured
by isothermal titration calorimetry (ITC). Weaker binding of ECP Q40A/H64A of all
heparin variants suggested that Gln(40)-His(64) clamp contributed to ECP-heparin
interaction significantly. Our in silico and in vitro data together demonstrate
that ECP uses not only major heparin binding region but also use other
surrounding residues to interact with heparin. Such correlation in sequence,
structure, and function is a unique feature of only higher primate ECP, but not
EDN.
PMID- 24349318
TI - Urinary miR-29 correlates with albuminuria and carotid intima-media thickness in
type 2 diabetes patients.
AB - BACKGROUND: Cell-free microRNAs stably and abundantly exist in body fluids and
emerging evidence suggests cell-free microRNAs as novel and non-invasive disease
biomarker. Deregulation of miR-29 is involved in the pathogenesis of diabetic
nephropathy and insulin resistance thus may be implicated in diabetic vascular
complication. Therefore, we investigated the possibility of urinary miR-29 as
biomarker for diabetic nephropathy and atherosclerosis in patients with type 2
diabetes. METHODS: 83 patients with type 2 diabetes were enrolled in this study,
miR-29a, miR-29b and miR-29c levels in urine supernatant was determined by TaqMan
qRT-PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control
before miRNAs extraction. Urinary albumin excretion rate and urine
albumin/creatinine ratio, funduscopy and carotid ultrasound were used for
evaluation of diabetic vascular complication. The laboratory parameters
indicating blood glucose level, renal function and serum lipids were also
collected. RESULTS: Patients with albuminuria (n = 42, age 60.62 +/- 12.00 yrs)
showed significantly higher comorbidity of diabetic retinopathy (p = 0.015) and
higher levels of urinary miR-29a (p = 0.035) compared with those with
normoalbuminuria (n = 41, age 58.54 +/- 14.40 yrs). There was no significant
difference in urinary miR-29b (p = 0.148) or miR-29c level (p = 0.321) between
groups. Urinary albumin excretion rate significantly correlated with urinary miR
29a level (r = 0.286, p = 0.016), while urinary miR-29b significantly correlated
with carotid intima-media thickness (cIMT) (r = 0.286, p = 0.046). CONCLUSION:
Urinary miR-29a correlated with albuminuria while urinary miR-29b correlated with
carotid intima-media thickness (cIMT) in patients with type 2 diabetes.
Therefore, they may have the potential to serve as alternative biomarker for
diabetic nephropathy and atherosclerosis in type 2 diabetes.
PMID- 24349319
TI - Horizontal gene acquisition of Liberibacter plant pathogens from a bacteriome
confined endosymbiont of their psyllid vector.
AB - he Asian citrus psyllid Diaphorina citri is a notorious agricultural pest that
transmits the phloem-inhabiting alphaproteobacterial 'Candidatus Liberibacter
asiaticus' and allied plant pathogens, which cause the devastating citrus disease
called Huanglongbing or greening disease. D. citri harbors two distinct bacterial
mutualists in the symbiotic organ called bacteriome: the betaproteobacterium
'Candidatus Profftella armatura' in the syncytial cytoplasm at the center of the
bacteriome, and the gammaproteobacterium 'Candidatus Carsonella ruddii' in
uninucleate bacteriocytes. Here we report that a putative amino acid transporter
LysE of Profftella forms a highly supported clade with proteins of L. asiaticus,
L. americanus, and L. solanacearum. L. crescens, the most basal Liberibacter
lineage currently known, lacked the corresponding gene. The Profftella
Liberibacter subclade of LysE formed a clade with proteins from
betaproteobacteria of the order Burkholderiales, to which Profftella belongs.
This phylogenetic pattern favors the hypothesis that the Liberibacter lineage
acquired the gene from the Profftella lineage via horizontal gene transfer (HGT)
after L. crescens diverged from other Liberibacter lineages. K A/K S analyses
further supported the hypothesis that the genes encoded in the Liberibacter
genomes are functional. These findings highlight the possible evolutionary
importance of HGT between plant pathogens and their insect vector's symbionts
that are confined in the symbiotic organ and seemingly sequestered from external
microbial populations.
PMID- 24349320
TI - Folate deficiency during early-mid pregnancy affects the skeletal muscle
transcriptome of piglets from a reciprocal cross.
AB - Folate deficiency (FD) during pregnancy can cause fetal intrauterine growth
restriction in pigs, of which the skeletal dysplasia is a major manifestation.
Factors influencing muscle development are very important in the formation of
porcine meat quality trait. However, the effect of folate deficiency on skeletal
muscle development and its molecular mechanisms are unknown. The objective of
this study is to determine the effect of maternal folate deficiency on the
skeletal muscle transcriptome of piglets from a reciprocal cross, in which full
sibling Landrace (LR) and full-sibling Chinese local breed Laiwu (LW) pigs were
used for reciprocal cross matings, and sows were fed either a folate deficient or
a normal diet during early-mid gestation. In addition, the difference in the
responsiveness of the piglets to folate deficiency during early-mid pregnancy
between reciprocal cross groups was investigated. Longissimus dorsi (LD) muscle
samples were collected from newborn piglets and a 4 * 44K Agilent porcine oligo
microarray was used for transcriptome analysis of porcine LD muscle. The results
showed that folate deficiency during early-mid pregnancy affected piglet body
weight, LD muscle fiber number and content of intramuscular triglyceride. The
microarray results indicated that 3154 genes were differentially expressed
between folate deficient and normal piglets from the LR? * LW? cross, and 3885
differentially expressed genes (DEGs) in the ones from the LW? * LR? cross. From
functional analyses, sow folate deficiency affected almost all biological
processes in the progeny. Lipid metabolism-related genes and associated metabolic
pathways were regulated extensively by folate deficiency, especially in LR? * LW?
cross piglets. Most of the genes that are regulated by folate deficiency in the
LD muscle of piglets were different between LR? * LW? and LW? * LR? crosses,
suggesting some epigenetic effects of FD exist in genes underlying myogenesis and
intramuscular fat deposition in piglets.
PMID- 24349321
TI - Difference in protein expression profile and chemotherapy drugs response of
different progression stages of LNCaP sublines and other human prostate cancer
cells.
AB - Androgen ablation therapy is the primary treatment for metastatic prostate
cancer. However, 80-90% of the patients who receive androgen ablation therapy
ultimately develop recurrent tumors in 12-33 months after treatment with a median
overall survival time of 1-2 years after relapse. LNCaP is a commonly used cell
line established from a human lymph node metastatic lesion of prostatic
adenocarcinoma. We previously established two relapsed androgen receptor (AR)
rich androgen-independent LNCaP sublines 104-R1 (androgen depleted for 12 months)
and 104-R2 cells (androgen depleted for 24 months) from AR-positive androgen
dependent LNCaP 104-S cells. LNCaP 104-R1 and 104-R2 mimics the AR-positive
hormone-refractory relapsed tumors in patients receiving androgen ablation
therapy. Androgen treatment stimulates proliferation of 104-S cells, but causes
growth inhibition and G1 cell cycle arrest in 104-R1 and 104-R2 cells. We
investigated the protein expression profile difference between LNCaP 104-S vs.
LNCaP 104-R1, 104-R2, PC-3, and DU-145 cells as well as examined the sensitivity
of these prostate cancer cells to different chemotherapy drugs and small molecule
inhibitors. Compared to 104-S cells, 104-R1 and 104-R2 cells express higher
protein levels of AR, PSA, c-Myc, Skp2, BCL-2, P53, p-MDM2 S166, Rb, and p-Rb
S807/811. The 104-R1 and 104-R2 cells express higher ratio of p-Akt S473/Akt, p
EGFR/EGFR, and p-Src/Src, but lower ratio of p-ERK/ERK than 104-S cells. PC-3 and
DU-145 cells express higher c-Myc, Skp2, Akt, Akt1, and phospho-EGFR but less
phospho-Akt and phospho-ERK. Overexpression of Skp2 increased resistance of LNCaP
cells to chemotherapy drugs. Paclitaxel, androgen, and inhibitors for PI3K/Akt,
EGFR, Src, or Bcl-2 seem to be potential choices for treatment of advanced
prostate cancers. Our study provides rationale for targeting Akt, EGFR, Src, Bcl
2, and AR signaling as a treatment for AR-positive relapsed prostate tumors after
hormone therapy.
PMID- 24349322
TI - First identification of "Brachyspira hampsonii" in wild European waterfowl.
AB - Anseriformes deserve special attention in the epidemiology of Brachyspira spp.
because diverse Anseriformes species have been described to act as highly
efficient carriers of several Brachyspira spp. that can also infect livestock.
The aim of this study was to investigate the prevalence and diversity of
Brachyspira spp. in waterfowl that winter in Spain. Brachyspira spp. were
isolated from 51 of the 205 faecal samples collected from graylag geese and
mallards in the Villafafila Lagoons Nature Reserve (Northwestern Spain). The
Brachyspira species identified through phenotyping, PCR and sequencing of the nox
gene were B. pilosicoli (5.9%), B. alvinipulli (11.8%), "B. hampsonii" (19.6%),
B. murdochii (23.5%) and B. innocens (39.2%). The most relevant finding of this
study is the description of "B. hampsonii" in specimens from birds for the first
time. Phylogenetic analysis of the nox gene sequences grouped all of the obtained
"B. hampsonii" isolates into a cluster with Brachyspira strains previously
identified by others as "B. hampsonii" and separated from other Brachyspira spp.
isolates and reference strains. Additionally, this cluster was related to clades
that grouped B. murdochii and B. innocens isolates. The identification of "B.
hampsonii" was also achieved in 8 of the 10 isolates by sequencing the16S rRNA
gene and tlyA gene. Regardless of the species identified, no antimicrobial
resistance was observed in any of the enteropathogenic isolates recovered. This
is the first description of "B. hampsonii" in European waterfowl, which might
represent hosts that serve as natural reservoirs of this Brachyspira species.
This finding indicates that this spirochete is not limited to North America, and
its presence in wild birds in Europe poses a risk of transmission to livestock.
PMID- 24349323
TI - An inducible expression system to measure rhodopsin transport in transgenic
Xenopus rod outer segments.
AB - We developed an inducible transgene expression system in Xenopus rod
photoreceptors. Using a transgene containing mCherry fused to the carboxyl
terminus of rhodopsin (Rho-mCherry), we characterized the displacement of
rhodopsin (Rho) from the base to the tip of rod outer segment (OS) membranes.
Quantitative confocal imaging of live rods showed very tight regulation of Rho
mCherry expression, with undetectable expression in the absence of dexamethasone
(Dex) and an average of 16.5 uM of Rho-mCherry peak concentration after induction
for several days (equivalent to >150-fold increase). Using repetitive inductions,
we found the axial rate of disk displacement to be 1.0 um/day for tadpoles at 20
degrees C in a 12 h dark /12 h light lighting cycle. The average distance to peak
following Dex addition was 3.2 um, which is equivalent to ~3 days. Rods treated
for longer times showed more variable expression patterns, with most showing a
reduction in Rho-mCherry concentration after 3 days. Using a simple model, we
find that stochastic variation in transgene expression can account for the shape
of the induction response.
PMID- 24349324
TI - A new in vitro model to study cellular responses after thermomechanical damage in
monolayer cultures.
AB - Although electrosurgical instruments are widely used in surgery to cut tissue
layers or to achieve hemostasis by coagulation (electrocautery), only little
information is available concerning the inflammatory or immune response towards
the debris generated. Given the elevated local temperatures required for
successful electrocautery, the remaining debris is likely to contain a plethora
of compounds entirely novel to the intracorporal setting. A very common in vitro
method to study cell migration after mechanical damage is the scratch assay,
however, there is no established model for thermomechanical damage to
characterise cellular reactions. In this study, we established a new in vitro
model to investigate exposure to high temperature in a carefully controlled cell
culture system. Heatable thermostat-controlled aluminium stamps were developed to
induce local damage in primary human umbilical vein endothelial cells (HUVEC).
The thermomechanical damage invoked is reproducibly locally confined, therefore
allowing studies, under the same experimental conditions, of cells affected to
various degrees as well as of unaffected cells. We show that the unaffected cells
surrounding the thermomechanical damage zone are able to migrate into the damaged
area, resulting in a complete closure of the 'wound' within 48 h. Initial studies
have shown that there are significant morphological and biological differences in
endothelial cells after thermomechanical damage compared to the mechanical damage
inflicted by using the unheated stamp as a control. Accordingly, after
thermomechanical damage, cell death as well as cell protection programs were
activated. Mononuclear cells adhered in the area adjacent to thermomechanical
damage, but not to the zone of mechanical damage. Therefore, our model can help
to understand the differences in wound healing during the early phase of
regeneration after thermomechanical vs. mechanical damage. Furthermore, this
model lends itself to study the response of other cells, thus broadening the
range of thermal injuries that can be analysed.
PMID- 24349325
TI - Evaluation of current and new biomarkers in severe preeclampsia: a microarray
approach reveals the VSIG4 gene as a potential blood biomarker.
AB - Preeclampsia is a placental disease characterized by hypertension and proteinuria
in pregnant women, and it is associated with a high maternal and neonatal
morbidity. However, circulating biomarkers that are able to predict the prognosis
of preeclampsia are lacking. Thirty-eight women were included in the current
study. They consisted of 19 patients with preeclampsia (13 with severe
preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched
women with normal pregnancies as controls. We measured circulating factors that
are associated with the coagulation pathway (including fibrinogen, fibronectin,
factor VIII, antithrombin, protein S and protein C), endothelial activation (such
as soluble endoglin and CD146), and the release of total and platelet-derived
microparticles. These markers enabled us to discriminate the preeclampsia
condition from a normal pregnancy but were not sufficient to distinguish severe
from non-severe preeclampsia. We then used a microarray to study the
transcriptional signature of blood samples. Preeclampsia patients exhibited a
specific transcriptional program distinct from that of the control group of
women. Interestingly, we also identified a severity-related transcriptional
signature. Functional annotation of the upmodulated signature in severe
preeclampsia highlighted two main functions related to "ribosome" and
"complement". Finally, we identified 8 genes that were specifically upmodulated
in severe preeclampsia compared with non-severe preeclampsia and the normotensive
controls. Among these genes, we identified VSIG4 as a potential diagnostic marker
of severe preeclampsia. The determination of this gene may improve the prognostic
assessment of severe preeclampsia.
PMID- 24349326
TI - Dipeptidyl peptidase IV inhibition activates CREB and improves islet
vascularization through VEGF-A/VEGFR-2 signaling pathway.
AB - Substitution of pancreatic islets is a potential therapy to treat diabetes and it
depends on reconstitution of islet's capillary network. In this study, we
addressed the question whether stabilization of Glucagon-Like-Peptide-1 (GLP-1)
by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) increases beta-cell mass by
modulating vascularization. Mouse or porcine donor islets were implanted under
kidney capsule of diabetic mice treated with DPP-IV inhibitor sitagliptin. Grafts
were analyzed for insulin production, beta-cell proliferation and
vascularization. In addition, the effect of sitagliptin on sprouting and Vascular
Endothelial Growth Factor (VEGF)-A expression was examined ex vivo. The cAMP
response element-binding (CREB) and VEGF-A/ Vascular Endothelial Growth Factor
Receptor (VEGFR)-2 signaling pathway leading to islet vascularization was
explored. Sitagliptin increased mean insulin content of islet grafts and area of
insulin-positive tissue as well as beta-cell proliferation. Interestingly,
sitagliptin treatment also markedly increased endothelial cell proliferation,
microvessel density and blood flow. Finally, GLP-1 (7-36) stimulated sprouting
and VEGF expression, which was significantly enhanced by sitagliptin- mediated
inhibition of DPP-IV. Our in vivo data demonstrate that sitagliptin treatment
phosphorylated CREB and induced islet vascularization through VEGF-A/VEGFR-2
signaling pathway. This study paves a new pathway for improvement of islet
transplantation in treating diabetes mellitus.
PMID- 24349327
TI - Helicobacter pylori genotypes associated with gastric histo-pathological damages
in a Moroccan population.
AB - H. pylori persistent infection induces chronic gastritis and is associated with
peptic ulcer disease and gastric carcinoma development. The severity of these
diseases is related to human's genetic diversity, H. pylori genetic variability
and environmental factors. To identify the prevalence of histo-pathological
damages caused by H. pylori infection in Moroccan population, and to determine
their association to H. pylori genotypes, a prospective study has been conducted
during 3 years on patients attending the gastroenterology department of Hassan II
University Hospital (CHU) of Fez, Morocco. A total of 801 Moroccan adults'
patients were recruited; H. pylori was diagnosed and genotyped by PCR in biopsy
specimens and histological exam was performed. We found a high rate of glandular
atrophy. Chronic inflammation, neutrophil activity and glandular atrophy showed
statistically significant association with H. pylori infection. However,
intestinal metaplasia was inversely associated to this infection and no
association was observed with gastric cancer cases. A statistically significant
association was found between intestinal metaplasia and vacAs1 and vac Am1
genotypes in patients aged 50 years and more but not in younger. This last
genotype is also associated to gastric cancer. In this study, gastric cancer
showed no significant association with H. pylori. Further studies are warranted
to determine the role of other etiological agents such as Epstein-Barr virus,
human papillomavirus and possibly environmental and dietetic factors in the
occurrence of this pathology.
PMID- 24349328
TI - Phthalates induce neurotoxicity affecting locomotor and thermotactic behaviors
and AFD neurons through oxidative stress in Caenorhabditis elegans.
AB - BACKGROUND: Phthalate esters are ubiquitous environmental contaminants and
numerous organisms are thus exposed to various levels of phthalates in their
natural habitat. Considering the critical, but limited, research on human
neurobehavioral outcomes in association with phthalates exposure, we used the
nematode Caenorhabditis elegans as an in vivo model to evaluate phthalates
induced neurotoxicity and the possible associated mechanisms. PRINCIPAL FINDINGS:
Exposure to phthalates (DEHP, DBP, and DIBP) at the examined concentrations
induced behavioral defects, including changes in body bending, head thrashing,
reversal frequency, and thermotaxis in C. elegans. Moreover, phthalates (DEHP,
DBP, and DIBP) exposure caused toxicity, affecting the relative sizes of cell
body fluorescent puncta, and relative intensities of cell bodies in AFD neurons.
The mRNA levels of the majority of the genes (TTX-1, TAX-2, TAX-4, and CEH-14)
that are required for the differentiation and function of AFD neurons were
decreased upon DEHP exposure. Furthermore, phthalates (DEHP, DBP, and DIBP)
exposure at the examined concentrations produced elevated intracellular reactive
oxygen species (ROS) in C. elegans. Finally, pretreatment with the antioxidant
ascorbic acid significantly lowered the intracellular ROS level, ameliorated the
locomotor and thermotactic behavior defects, and protected the damage of AFD
neurons by DEHP exposure. CONCLUSIONS: Our study suggests that oxidative stress
plays a critical role in the phthalate esters-induced neurotoxic effects in C.
elegans.
PMID- 24349329
TI - A vaccine that co-targets tumor cells and cancer associated fibroblasts results
in enhanced antitumor activity by inducing antigen spreading.
AB - Dendritic cell (DC) vaccines targeting only cancer cells have produced limited
antitumor activity in most clinical studies. Targeting cancer-associated
fibroblasts (CAFs) in addition to cancer cells may enhance antitumor effects,
since CAFs, the central component of the tumor stroma, directly support tumor
growth and contribute to the immunosuppressive tumor microenvironment. To co
target CAFs and tumor cells we developed a new compound DC vaccine that encodes
an A20-specific shRNA to enhance DC function, and targets fibroblast activation
protein (FAP) expressed in CAFs and the tumor antigen tyrosine-related protein
(TRP)2 (DC-shA20-FAP-TRP2). DC-shA20-FAP-TRP2 vaccination induced robust FAP- and
TRP2-specific T-cell responses, resulting in greater antitumor activity in the
B16 melanoma model in comparison to monovalent vaccines or a vaccine encoding
antigens and a control shRNA. DC-shA20-FAP-TRP2 vaccination enhanced tumor
infiltration of CD8-positive T cells, and induced antigen-spreading resulting in
potent antitumor activity. Thus, co-targeting of tumor cells and CAFs results in
the induction of broad-based tumor-specific T-cell responses and has the
potential to improve current vaccine approaches for cancer.
PMID- 24349330
TI - Cortical mapping of mismatch negativity with deviance detection property in rat.
AB - Mismatch Negativity (MMN) is an N-methyl-d-aspartic acid (NMDA)-mediated,
negative deflection in human auditory evoked potentials in response to a
cognitively discriminable change. MMN-like responses have been extensively
investigated in animal models, but the existence of MMN equivalent is still
controversial. In this study, we aimed to investigate how closely the putative
MMN (MMNp) in rats exhibited the comparable properties of human MMN. We used a
surface microelectrode array with a grid of 10 * 7 recording sites within an area
of 4.5 * 3.0 mm to densely map evoked potentials in the auditory cortex of
anesthetized rats under the oddball paradigm. Firstly, like human MMN, deviant
stimuli elicited negative deflections in auditory evoked potentials following the
positive middle-latency response, termed P1. Secondly, MMNp exhibited deviance
detecting property, which could not be explained by simple stimulus specific
adaptation (SSA). Thirdly, this MMNp occurred focally in the auditory cortex,
including both the core and belt regions, while P1 activation focus was obtained
in the core region, indicating that both P1 and MMNp are generated in the
auditory cortex, yet the sources of these signals do not completely overlap.
Fourthly, MMNp significantly decreased after the application of AP5 (D-(-)-2
amino-5-phosphonopentanoic acid), an antagonist at NMDA receptors. In stark
contrast, AP5 affected neither P1 amplitude nor SSA of P1. These results provide
compelling evidence that the MMNp we have examined in rats is functionally
comparable to human MMN. The present work will stimulate translational research
into MMN, which may help bridge the gap between electroencephalography
(EEG)/magnetoencephalography (MEG) studies in humans and electrophysiological
studies in animals.
PMID- 24349331
TI - Infective endocarditis epidemiology over five decades: a systematic review.
AB - AIMS: To Assess changes in infective endocarditis (IE) epidemiology over the last
5 decades. METHODS AND RESULTS: We searched the published literature using
PubMed, MEDLINE, and EMBASE from inception until December 2011. DATA FROM:
Einstein Medical Center, Philadelphia, PA were also included. Criteria for
inclusion in this systematic review included studies with reported IE
microbiology, IE definition, description of population studied, and time frame.
Two authors independently extracted data and assessed manuscript quality. One
hundred sixty studies (27,083 patients) met inclusion criteria. Among hospital
based studies (n=142; 23,606 patients) staphylococcal IE percentage increased
over time, with coagulase-negative staphylococcus (CNS) increasing over each of
the last 5 decades (p<0.001) and Staphylococcus aureus (SA) in the last decade
(21% to 30%; p<0.05). Streptococcus viridans (SV) and culture negative (CN) IE
frequency decreased over time (p<0.001), while enterococcal IE increased in the
last decade (p<0.01). Patient age and male predominance increased over time as
well. In subgroup analysis, SA frequency increased in North America, but not the
rest of the world. This was due, in part, to an increase in intravenous drug
abuse IE in North America (p<0.001). Among population-based studies (n=18; 3,477
patients) no significant changes were found. CONCLUSION: Important changes
occurred in IE epidemiology over the last half-century, especially in the last
decade. Staphylococcal and enterococcal IE percentage increased while SV and CN
IE decreased. Moreover, mean age at diagnosis increased together with male:female
ratio. These changes should be considered at the time of decision-making in
treatment of and prophylaxis for IE.
PMID- 24349332
TI - Human Fanconi anemia complementation group a protein stimulates the 5' flap
endonuclease activity of FEN1.
AB - In eukaryotic cells, Flap endonuclease 1 (FEN1) is a major structure-specific
endonuclease that processes 5' flapped structures during maturation of lagging
strand DNA synthesis, long patch base excision repair, and rescue of stalled
replication forks. Here we report that fanconi anemia complementation group A
protein (FANCA), a protein that recognizes 5' flap structures and is involved in
DNA repair and maintenance of replication forks, constantly stimulates FEN1
mediated incision of both DNA and RNA flaps. Kinetic analyses indicate that FANCA
stimulates FEN1 by increasing the turnover rate of FEN1 and altering its
substrate affinity. More importantly, six pathogenic FANCA mutants are
significantly less efficient than the wild-type at stimulating FEN1 endonuclease
activity, implicating that regulation of FEN1 by FANCA contributes to the
maintenance of genomic stability.
PMID- 24349333
TI - The effect of high intensity interval exercise on postprandial triacylglycerol
and leukocyte activation--monitored for 48 h post exercise.
AB - Postprandial phenomenon are thought to contribute to atherogenesis alongside
activation of the immune system. A single bout of high intensity interval
exercise attenuates postprandial triacylglycerol (TG), although the longevity and
mechanisms underlying this observation are unknown. The aims of this study were
to determine whether this attenuation in postprandial TG remained 2 days after
high intensity interval exercise, to monitor markers of leukocyte activation and
investigate the underlying mechanisms. Eight young men each completed two three
day trials. On day 1: subjects rested (Control) or performed 5 x 30 s maximal
sprints (high intensity interval exercise). On day 2 and 3 subjects consumed high
fat meals for breakfast and 3 h later for lunch. Blood samples were taken at
various times and analysed for TG, glucose and TG-rich lipoprotein (TRL)-bound
LPL-dependent TRL-TG hydrolysis (LTTH). Flow cytometry was used to evaluate
granulocyte, monocyte and lymphocyte CD11b and CD36 expression. On day 2 after
high intensity interval exercise TG area under the curve was lower (P<0.05) (7.46
+/- 1.53 mmol/l/7h) compared to the control trial (9.47 +/- 3 .04 mmol/l/7h) with
no differences during day 3 of the trial. LTTH activity was higher (P<0.05) after
high intensity interval exercise, at 2 hours of day 2, compared to control.
Granulocyte, monocyte and lymphocyte CD11b expression increased with time over
day 2 and 3 of the study (P<0.0001). Lymphocyte and monocyte CD36 expression
decreased with time over day 2 and 3 (P<0.05). There were no differences between
trials in CD11b and CD36 expression on any leukocytes. A single session of high
intensity interval exercise attenuated postprandial TG on day 2 of the study,
with this effect abolished by day 3.The reduction in postprandial TG was
associated with an increase in LTTH. High intensity interval exercise had no
effect on postprandial responses of CD11b or CD36.
PMID- 24349334
TI - Genetic and non-genetic determinants of raltegravir penetration into
cerebrospinal fluid: a single arm pharmacokinetic study.
AB - BACKGROUND: Antiretroviral drugs vary in their central nervous system
penetration, with better penetration possibly conferring neurocognitive benefit
during human immunodeficiency virus (HIV) therapy. The efflux transporter gene
ABCB1 is expressed in the blood-brain barrier, and an ABCB1 variant (3435C -> T)
has been reported to affect ABCB1 expression. The integrase inhibitor raltegravir
is a substrate for ABCB1. We examined whether ABCB1 3435C -> T affects
raltegravir disposition into cerebrospinal fluid (CSF), and explored associations
with polymorphisms in other membrane transporter genes expressed in the blood
brain barrier. METHODS: Forty healthy, HIV-negative adults of European descent
(20 homozygous for ABCB1 3435 C/C, 20 homozygous for 3435 T/T, each group divided
equally between males and females) were given raltegravir 400 mg twice daily for
7 days. With the final dose, plasma was collected for pharmacokinetic analysis at
9 timepoints over 12 hours, and CSF collected 4 hours post dose. RESULTS: The 4
hour CSF concentration correlated more strongly with 2-hour (r(2)=0.76, P=1.12 x
10(-11)) than 4-hour (r(2)=0.47, P=6.89 x 10(-6)) single timepoint plasma
concentration, and correlated strongly with partial plasma area-under-the-curve
values (AUC0-4h r(2)=0.86, P=5.15 x 10(-16)). There was no significant
association between ABCB1 3435C -> T and ratios of CSF-to-plasma AUC or
concentration (p>0.05 for each comparison). In exploratory analyses, CSF-to
plasma ratios were not associated with 276 polymorphisms across 16 membrane
transporter genes. CONCLUSIONS: Among HIV-negative adults, CSF raltegravir
concentrations do not differ by ABCB1 3435C -> T genotype but strongly correlate
with plasma exposure. TRIAL REGISTRATION: ClinicalTrials.gov NCT00729924
http://clinicaltrials.gov/show/NCT00729924.
PMID- 24349335
TI - Acute and prolonged adverse effects of temperature on mortality from
cardiovascular diseases.
AB - BACKGROUND: Cardiovascular diseases are the leading causes of death worldwide,
especially for developed countries. Elevated mortality from cardiovascular
diseases has been shown related to extreme temperature. We thus assessed the risk
of mortality from cerebrovascular diseases, heart diseases, and ischemic heart
disease (IHD) in relation to temperature profiles in four subtropical
metropolitans (Taipei, Taichung, Tainan, and Kaohsiung) from 1994 to 2007 in
Taiwan. METHODS: Distributed lag non-linear models were applied to estimate the
cumulative relative risks (RRs) with confidence intervals of cause-specific
mortality associated with daily temperature from lag 0 to 20 days, and specific
effect of extreme temperature episodes with PM10, NOx, and O3, and other
potential confounders controlled. Estimates for cause-specific mortalities were
then pooled by random-effect meta-analysis. RESULTS: Comparing to centered
temperature at 27 degrees C, the cumulative 4-day (lag 0 to 3) risk of mortality
was significantly elevated at 31 degrees C for cerebrovascular diseases (RR =
1.14; 95% CI: 1.00, 1.31) and heart diseases (RR = 1.22; 95% CI: 1.02, 1.46) ,
but not for IHD (RR = 1.09; 95% CI: 0.99, 1.21). To the other extreme, at 15
degrees C, the cumulative 21-day (lag 0 to 20) risk of mortality were also
remarkably increased for cerebrovascular diseases, heart diseases, and IHD (RRs
= 1.48 with 95% CI: 1.04, 2.12, 2.04 with 95% CI: 1.61, 2.58, and 1.62 with 95%
CI: 1.30, 2.01, respectively). Mortality risks for cardiovascular diseases were
generally highest on the present day (lag 0) of extreme heat. No particular
finding was detected on prolonged extreme temperature event by pooling
estimations for cause-specific mortality. CONCLUSIONS: Low temperature was
associated with greater risk of mortality from cardiovascular diseases in
comparison with that of high temperature. Adverse effects of extreme temperatures
are acute at the beginning of exposure.
PMID- 24349336
TI - Short-term azithromycin treatment promotes cornea allograft survival in the rat.
AB - BACKGROUND: Any inflammatory response following corneal transplantation may
induce rejection and irreversible graft failure. The purpose of this study is to
analyze the anti-inflammatory effect of azithromycin (AZM) following experimental
keratoplasty in rats. METHODS: Corneal transplants were performed between Fisher
donor and Lewis-recipient rats. Recipients were postoperatively treated three
times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an
additional control, AZM was applied following syngeneic keratoplasty.
Furthermore, short-term treatments with AZM for seven days perioperatively or
with AZM only three days prior to the transplantation were compared to
appropriate controls. All transplants were monitored clinically for opacity,
edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+),
CD161(+) and CD163(+) cells were quantified via immunohistochemistry. RESULTS:
AZM significantly promoted corneal graft survival compared with miglyol or
ofloxacin treatment. This effect was comparable to topical dexamethasone. No
adverse AZM effect was observed. Histology confirmed a significant reduction of
infiltrating leukocytes. The short-term application of AZM for three days prior
to transplantation or for seven days perioperatively reduced corneal graft
rejection significantly compared with the controls. CONCLUSIONS: Along with
antibiotic properties, topical AZM has a strong anti-inflammatory effect.
Following keratoplasty, this effect is comparable to topical dexamethasone
without the risk of steroid-induced adverse effects. Short-term treatment with
AZM three days prior to the transplantation was sufficient to promote graft
survival in the rat keratoplasty model. We therefore suggest further assessing
the anti-inflammatory function of topical AZM following keratoplasty in humans.
PMID- 24349337
TI - Transmural ultrasound imaging of thermal lesion and action potential changes in
perfused canine cardiac wedge preparations by high intensity focused ultrasound
ablation.
AB - Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It
is difficult to obtain intra-procedural correlation of thermal lesion formation
with action potential (AP) changes in the transmural plane during ablation. This
study tested parametric ultrasound imaging for transmural imaging of lesion and
AP changes in high intensity focused ultrasound (HIFU) ablation using coronary
perfused canine ventricular wedge preparations (n = 13). The preparations were
paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz,
11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm(2)),
during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and
ultrasound imaging (30 MHz) of the same transmural surface of the wedge were
performed. Spatiotemporally correlated AP measurements and ultrasound imaging
allowed quantification of the reduction of AP amplitude (APA), shortening of AP
duration at 50% repolarization, AP triangulation, decrease of optical AP rise,
and change of conduction velocity along tissue depth direction within and
surrounding HIFU lesions. The threshold of irreversible change in APA correlating
to lesions was determined to be 43 +/- 1% with a receiver operating
characteristic (ROC) area under curve (AUC) of 0.96 +/- 0.01 (n = 13). Ultrasound
imaging parameters such as integrated backscatter, Rayleigh (alpha) and log
normal (sigma) parameters, cumulative extrema of sigma were tested, with the
cumulative extrema of sigma performing the best in detecting lesion (ROC AUC 0.89
+/- 0.01, n = 13) and change of APA (ROC AUC 0.79 +/- 0.03, n = 13). In
conclusion, characteristic tissue and AP changes in HIFU ablation were identified
and spatiotemporally correlated using optical mapping and ultrasound imaging.
Parametric ultrasound imaging using cumulative extrema of sigma can detect HIFU
lesion and APA reduction.
PMID- 24349338
TI - Structural characterization of a therapeutic anti-methamphetamine antibody
fragment: oligomerization and binding of active metabolites.
AB - Vaccines and monoclonal antibodies (mAb) for treatment of (+)-methamphetamine
(METH) abuse are in late stage preclinical and early clinical trial phases,
respectively. These immunotherapies work as pharmacokinetic antagonists,
sequestering METH and its metabolites away from sites of action in the brain and
reduce the rewarding and toxic effects of the drug. A key aspect of these
immunotherapy strategies is the understanding of the subtle molecular
interactions important for generating antibodies with high affinity and
specificity for METH. We previously determined crystal structures of a high
affinity anti-METH therapeutic single chain antibody fragment (scFv6H4, K(D) = 10
nM) in complex with METH and the (+) stereoisomer of 3,4
methylenedioxymethamphetamine (MDMA, or "ecstasy"). Here we report the crystal
structure of scFv6H4 in homo-trimeric unbound (apo) form (2.60A), as well as
monomeric forms in complex with two active metabolites; (+)-amphetamine (AMP,
2.38A) and (+)-4-hydroxy methamphetamine (p-OH-METH, 2.33A). The apo structure
forms a trimer in the crystal lattice and it results in the formation of an
intermolecular composite beta-sheet with a three-fold symmetry. We were also able
to structurally characterize the coordination of the His-tags with Ni(2+). Two of
the histidine residues of each C-terminal His-tag interact with Ni(2+) in an
octahedral geometry. In the apo state the CDR loops of scFv6H4 form an open
conformation of the binding pocket. Upon ligand binding, the CDR loops adopt a
closed formation, encasing the drug almost completely. The structural information
reported here elucidates key molecular interactions important in anti
methamphetamine abuse immunotherapy.
PMID- 24349339
TI - Loss of heterozygosity drives clonal diversity of Phytophthora capsici in China.
AB - Phytophthora capsici causes significant loss to pepper (Capsicum annum) in China
and our goal was to develop single nucleotide polymorphism (SNP) markers for P.
capsici and characterize genetic diversity nationwide. Eighteen isolates of P.
capsici from locations worldwide were re-sequenced and candidate nuclear and
mitochondrial SNPs identified. From 2006 to 2012, 276 isolates of P. capsici were
recovered from 136 locations in 27 provinces and genotyped using 45 nuclear and 2
mitochondrial SNPs. There were two main mitochondrial haplotypes and 95 multi
locus genotypes (MLGs) identified. Genetic diversity was geographically
structured with a high level of genotypic diversity in the north and on Hainan
Island in the south, suggesting outcrossing contributes to diversity in these
areas. The remaining areas of China are dominated by four clonal lineages that
share mitochondrial haplotypes, are almost exclusively the A1 or A2 mating type
and appear to exhibit extensive diversity based on loss of heterozygosity (LOH).
Analysis of SNPs directly from infected peppers confirmed LOH in field
populations. One clonal lineage is dominant throughout much of the country. The
overall implications for long-lived genetically diverse clonal lineages amidst a
widely dispersed sexual population are discussed.
PMID- 24349340
TI - Predictors of acute respiratory distress syndrome in patients with paraquat
intoxication.
AB - INTRODUCTION: Paraquat poisoning is characterized by acute lung injury, pulmonary
fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate
of mortality and morbidity. The objectives of this study were to identify
predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat
poisoning and determine the association between these parameters. MATERIALS AND
METHODS: In total, 187 patients were referred for management of intentional
paraquat ingestion between 2000 and 2010. Demographic, clinical, and laboratory
data were recorded. Sequential organ failure assessment (SOFA) and Acute Kidney
Injury Network (AKIN) scores were collected, and predictors of ARDS were
analyzed. RESULTS: The overall mortality rate for the entire population was 54%
(101/187). Furthermore, the mortality rate was higher in the ARDS patients than
in the non-ARDS patients (80% vs. 43.80%, P<0.001). Additionally, the ARDS
patients not only had higher AKIN48-h scores (P<0.009), SOFA48-h scores
(P<0.001), and time to ARDS/nadir PaO2 (P=0.008) but also suffered from lower
nadir PaO2 (P<0.001), nadir AaDO2 (P<0.001), and nadir eGFR (P=0.001) compared to
those in the non-ARDS patients. Moreover, pneumomediastinum episodes were more
frequent in the ARDS patients than in the non-ARDS patients (P<0.001). A
multivariate Cox regression model revealed that blood paraquat concentrations
(P<0.001), SOFA48-h scores (P=0.001), and steroid and cyclophosphamide pulse
therapies (P=0.024) were significant predictors of ARDS. The cumulative survival
rates differed significantly (P<0.001) between patients with SOFA48-h scores <3
and SOFA48-h scores >=3, with a sensitivity of 95.8%, specificity of 58.4%, and
overall correctness of 67.6%. Finally, the area under the receiver operating
characteristic (AUROC) analysis showed that SOFA48-h scores (P<0.001) had a
better discriminatory power than blood paraquat concentrations (P=0.01) for
predicting ARDS. CONCLUSIONS: The analytical results indicate that SOFA48-h
scores, blood paraquat concentrations, and steroid and cyclophosphamide pulse
therapies are significantly associated with ARDS complications after paraquat
intoxication.
PMID- 24349341
TI - Development of a real-time microchip PCR system for portable plant disease
diagnosis.
AB - Rapid and accurate detection of plant pathogens in the field is crucial to
prevent the proliferation of infected crops. Polymerase chain reaction (PCR)
process is the most reliable and accepted method for plant pathogen diagnosis,
however current conventional PCR machines are not portable and require additional
post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real
time PCR can directly quantify the amplicon during the DNA amplification without
the need for post processing, thus more suitable for field operations, however
still takes time and require large instruments that are costly and not portable.
Microchip PCR systems have emerged in the past decade to miniaturize conventional
PCR systems and to reduce operation time and cost. Real-time microchip PCR
systems have also emerged, but unfortunately all reported portable real-time
microchip PCR systems require various auxiliary instruments. Here we present a
stand-alone real-time microchip PCR system composed of a PCR reaction chamber
microchip with integrated thin-film heater, a compact fluorescence detector to
detect amplified DNA, a microcontroller to control the entire thermocycling
operation with data acquisition capability, and a battery. The entire system is
25 * 16 * 8 cm(3) in size and 843 g in weight. The disposable microchip requires
only 8-ul sample volume and a single PCR run consumes 110 mAh of power. A DNA
extraction protocol, notably without the use of liquid nitrogen, chemicals, and
other large lab equipment, was developed for field operations. The developed real
time microchip PCR system and the DNA extraction protocol were used to
successfully detect six different fungal and bacterial plant pathogens with 100%
success rate to a detection limit of 5 ng/8 ul sample.
PMID- 24349342
TI - Artificial sweeteners in a large Canadian river reflect human consumption in the
watershed.
AB - Artificial sweeteners have been widely incorporated in human food products for
aid in weight loss regimes, dental health protection and dietary control of
diabetes. Some of these widely used compounds can pass non-degraded through
wastewater treatment systems and are subsequently discharged to groundwater and
surface waters. Measurements of artificial sweeteners in rivers used for drinking
water production are scarce. In order to determine the riverine concentrations of
artificial sweeteners and their usefulness as a tracer of wastewater at the scale
of an entire watershed, we analyzed samples from 23 sites along the entire length
of the Grand River, a large river in Southern Ontario, Canada, that is impacted
by agricultural activities and urban centres. Municipal water from household taps
was also sampled from several cities within the Grand River Watershed. Cyclamate,
saccharin, sucralose, and acesulfame were found in elevated concentrations
despite high rates of biological activity, large daily cycles in dissolved oxygen
and shallow river depth. The maximum concentrations that we measured for
sucralose (21 ug/L), cyclamate (2.4 ug/L) [corrected], and saccharin (7.2 ug/L)
are the highest reported concentrations of these compounds in surface waters to
date anywhere in the world. Acesulfame persists at concentrations that are up to
several orders of magnitude above the detection limit over a distance of 300 km
and it behaves conservatively in the river, recording the wastewater contribution
from the cumulative population in the basin. Acesulfame is a reliable wastewater
effluent tracer in rivers. Furthermore, it can be used to assess rates of
nutrient assimilation, track wastewater plume dilution, separate human and animal
waste contributions and determine the relative persistence of emerging
contaminants in impacted watersheds where multiple sources confound the
usefulness of other tracers. The effects of artificial sweeteners on aquatic
biota in rivers and in the downstream Great Lakes are largely unknown.
PMID- 24349343
TI - An automated blur detection method for histological whole slide imaging.
AB - Whole slide scanners are novel devices that enable high-resolution imaging of an
entire histological slide. Furthermore, the imaging is achieved in only a few
minutes, which enables image rendering of large-scale studies involving multiple
immunohistochemistry biomarkers. Although whole slide imaging has improved
considerably, locally poor focusing causes blurred regions of the image. These
artifacts may strongly affect the quality of subsequent analyses, making a slide
review process mandatory. This tedious and time-consuming task requires the
scanner operator to carefully assess the virtual slide and to manually select new
focus points. We propose a statistical learning method that provides early image
quality feedback and automatically identifies regions of the image that require
additional focus points.
PMID- 24349344
TI - Enhanced expression of cystathionine beta-synthase and cystathionine gamma-lyase
during acute cholecystitis-induced gallbladder inflammation.
AB - BACKGROUND: Hydrogen sulfide (H2S) has recently been shown to play an important
role in the digestive system, but the role of endogenous H2S produced locally in
the gallbladder is unknown. The aim of this study was to investigate whether
gallbladder possesses the enzymatic machinery to synthesize H2S, and whether H2S
synthesis is changed in gallbladder inflammation during acute acalculous
cholecystitis (AC). METHODS: Adult male guinea pigs underwent either a sham
operation or common bile duct ligation (CBDL). One, two, or three days after
CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained
slides of gallbladder samples were scored for inflammation. H2S production rate
in gallbladder tissue from each group was determined; immunohistochemistry and
western blotting were used to determine expression levels of the H2S-producing
enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) in
gallbladder. RESULTS: There was a progressive inflammatory response after CBDL.
Immunohistochemistry analysis showed that CBS and CSE were expressed in the
gallbladder epithelium, muscular layer, and blood vessels and that the expression
increased progressively with increasing inflammation following CBDL. The
expression of CBS protein as well as the H2S-production rate was significantly
increased in the animals that underwent CBDL, compared to those that underwent
the sham operation. CONCLUSIONS: Both CBS and CSE are expressed in gallbladder
tissues. The expression of these enzymes, as well as H2S synthesis, was up
regulated in the context of inflammation during AC.
PMID- 24349345
TI - High transcript levels of vitamin D receptor are correlated with higher mRNA
expression of human beta defensins and IL-10 in mucosa of HIV-1-exposed
seronegative individuals.
AB - Vitamin D (VitD) is an endogenous immunomodulator that could protect from HIV-1
infection reducing immune activation and inducing the expression of anti-HIV-1
peptides. To establish a correlation between VitD and natural resistance to HIV-1
infection, a case-control study using blood and mucosa samples of 58 HIV-1
exposed but seronegative (HESN) individuals, 43 HIV-1 seropositives (SPs) and 59
non-exposed healthy controls (HCs) was carried out. The VitD concentration in
plasma was determined by ELISA, and mRNA relative units (RU) of VDR, IL-10, TGF
beta, TNF-alpha and IL-1beta in peripheral blood mononuclear cells (PBMCs), oral
and genital mucosa was quantified by qRT-PCR. mRNA levels of human beta-defensin
(HBD) -2 and -3 were previously reported and used for correlations. Significantly
higher levels of VitD were found in plasma as well as higher mRNA RU of VDR in
PBMCs, and in genital mucosa from HESN compared to HCs. In addition, higher mRNA
RU of TNF-alpha, IL-1beta and IL-10, and lower mRNA RU of TGF-beta were found in
PBMC from HESNs compared to HCs. We also observed higher IL-10 mRNA RU in genital
mucosa of HESNs compared to HCs, and the mRNA levels of TNF-alpha in oral and
genital mucosa of SPs were higher compared to HESNs. Furthermore, positive
correlations between VDR and IL-10 mRNA RU in PBMCs and genital mucosa of HESNs
were found. Finally, HBD-2 and HBD-3 mRNA RU were positively correlated with VDR
mRNA expression in oral mucosa from HESNs. These results suggest that high levels
of VitD and its receptor are associated with natural resistance to HIV-1
infection. Up-regulation of the anti-inflammatory IL-10, and the induction of
anti-HIV-1 defensins in mucosa might be part of the mechanisms involved in this
association. However, further studies are required to define causal associations.
PMID- 24349347
TI - Health information seeking partially mediated the association between
socioeconomic status and self-rated health among Hong Kong Chinese.
AB - BACKGROUND: Poor self-rated health (SRH) is socially patterned with health
communication inequalities, arguably, serving as one mechanisms. This study
investigated the effects of health information seeking on SRH, and its mediation
effects on disparities in SRH. METHODS: We conducted probability-based telephone
surveys administered over telephone in 2009, 2010/11 and 2012 to monitor health
information use among 4553 Chinese adults in Hong Kong. Frequency of information
seeking from television, radio, newspapers/magazines and Internet was
dichotomised as <1 time/month and >= 1 time/month. Adjusted odds ratios (aOR) for
poor SRH were calculated for health information seeking from different sources
and socioeconomic status (education and income). Mediation effects of health
information seeking on the association between SES and poor SRH was estimated.
RESULTS: Poor SRH was associated with lower socioeconomic status (P for trend
<0.001), and less than monthly health information seeking from
newspapers/magazines (aOR = 1.23, 95% CI 1.07-1.42) and Internet (aOR = 1.13, 95%
CI 0.98-1.31). Increasing combined frequency of health information seeking from
newspapers/magazines and Internet was linearly associated with better SRH (P for
trend <0.01). Health information seeking from these two sources contributed 9.2%
and 7.9% of the total mediation effects of education and household income on poor
SRH, respectively. CONCLUSIONS: Poor SRH was associated with lower socioeconomic
status, and infrequent health information seeking from newspapers/magazines and
Internet among Hong Kong Chinese. Disparities in SRH may be partially mediated by
health information seeking from newspapers/magazines and Internet.
PMID- 24349348
TI - Maternal investment in the swordtail fish Xiphophorus multilineatus: support for
the differential allocation hypothesis.
AB - The differential allocation hypothesis predicts that reproductive investment will
be influenced by mate attractiveness, given a cost to reproduction and a tradeoff
between current and future reproduction. We tested the differential allocation
hypothesis in the swordtail fish Xiphophorus multilineatus, where males have
genetically influenced (patroclinous inheritance) alternative mating tactics
(ARTs) maintained by a tradeoff between being more attractive to females (mature
later as larger courting males) and a higher probability of reaching sexual
maturity (mature earlier as smaller sneaker males). Males in X. multilineatus do
not provide parental care or other resources to the offspring. Allelic variation
and copy number of the Mc4R gene on the Y-chromosome influences the size
differences between males, however there is no variation in this gene on the X
chromosome. Therefore, to determine if mothers invested more in offspring of the
larger courter males, we examined age to sexual maturity for daughters. We
confirmed a tradeoff between number of offspring and female offspring's age to
sexual maturity, corroborating that there is a cost to reproduction. In addition,
the ART of their fathers significantly influenced the age at which daughters
reached sexual maturity, suggesting increased maternal investment to daughters of
courter males. The differential allocation we detected was influenced by how long
the wild-caught mother had been in the laboratory, as there was a brood order by
father genotype (ART) interaction. These results suggest that females can adjust
their reproductive investment strategy, and that differential allocation is
context specific. We hypothesize that one of two aspects of laboratory conditions
produced this shift: increased female condition due to higher quality diet,
and/or assessment of future mating opportunities due to isolation from males.
PMID- 24349346
TI - Nicotine elicits prolonged calcium signaling along ventral hippocampal axons.
AB - Presynaptic nicotinic acetylcholine receptors (nAChRs) have long been implicated
in the modulation of CNS circuits. We previously reported that brief exposure to
low concentrations of nicotine induced sustained potentiation of glutamatergic
transmission at ventral hippocampal (vHipp)-striatal synapses. Here, we exploited
nAChR subtype-selective antagonists and agonists and alpha7*nAChR knockout mutant
mice (alpha7-/-) to elucidate the signaling mechanisms underlying nAChR-mediated
modulation of synaptic transmission. Using a combination of micro-slices culture
from WT and alpha7-/-mice, calcium imaging, and immuno-histochemical techniques,
we found that nicotine elicits localized and oscillatory increases in
intracellular Ca(2+) along vHipp axons that persists for up to 30 minutes. The
sustained phase of the nicotine-induced Ca(2+) response was blocked by alpha-BgTx
but not by DHbetaE and was mimicked by alpha7*nAChR agonists but not by non
alpha7*nAChR agonists. In vHipp slices from alpha7-/- mice, nicotine elicited
only transient increases of axonal Ca(2+) signals and did not activate CaMKII.
The sustained phase of the nicotine-induced Ca(2+) response required localized
activation of CaMKII, phospholipase C, and IP3 receptor mediated Ca(2+)-induced
Ca(2+) release (CICR). In conclusion, activation of presynaptic nAChRs by
nicotine elicits Ca(2+) influx into the presynaptic axons, the sustained phase of
the nicotine-induced Ca(2+) response requires that axonal alpha7*nAChR activate a
downstream signaling network in the vHipp axons.
PMID- 24349349
TI - Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor
currents in mammalian cells.
AB - Crude extracts and three isolated alkaloids from Erythrina mulungu plants have
shown anxiolytic effects in different animal models. We investigated whether
these alkaloids could affect nicotinic acetylcholine receptors and if they are
selective for different central nervous system (CNS) subtypes. Screening
experiments were performed using a single concentration of the alkaloid co
applied with acetylcholine in whole cell patch-clamp recordings in three
different cell models: (i) PC12 cells natively expressing alpha3* nicotinic
acetylcholine receptors; (ii) cultured hippocampal neurons natively expressing
alpha7* nicotinic acetylcholine receptors; and (iii) HEK 293 cells heterologoulsy
expressing alpha4beta2 nicotinic acetylcholine receptors. For all three
receptors, the percent inhibition of acetylcholine-activated currents by (+)-11a
hydroxyerysotrine was the lowest, whereas (+)-erythravine and (+)-11a
hydroxyerythravine inhibited the currents to a greater extent. For the latter two
substances, we obtained concentration-response curves with a pre-application
protocol for the alpha7* and alpha4beta2 nicotinic acetylcholine receptors. The
IC50 obtained with (+)-erythravine and (+)-11a-hydroxyerythravine were 6 uM and 5
uM for the alpha7* receptors, and 13 nM and 4 nM for the alpha4beta2 receptors,
respectively. Our data suggest that these Erythrina alkaloids may exert their
behavioral effects through inhibition of CNS nicotinic acetylcholine receptors,
particularly the alpha4beta2 subtype.
PMID- 24349350
TI - Propofol protects against focal cerebral ischemia via inhibition of microglia
mediated proinflammatory cytokines in a rat model of experimental stroke.
AB - Ischemic stroke induces microglial activation and release of proinflammatory
cytokines, contributing to the expansion of brain injury and poor clinical
outcome. Propofol has been shown to ameliorate neuronal injury in a number of
experimental studies, but the precise mechanisms involved in its neuroprotective
effects remain unclear. We tested the hypothesis that propofol confers
neuroprotection against focal ischemia by inhibiting microglia-mediated
inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were
subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h of
reperfusion. Propofol (50 mg/kg/h) or vehicle was infused intravenously at the
onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in
significant cerebral infarction, higher neurological deficit scores and decreased
time on the rotarod compared with sham-operated rats. Propofol treatment reduced
infarct volume and improved the neurological functions. In addition, molecular
studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was
significantly increased, and mRNA and protein expressions of proinflammatory
cytokines tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 were
augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after
MCAO. Immunohistochemical study revealed that number of total microglia and
proportion of activated microglia in the peri-infarct cortical regions were
markedly elevated. All of these findings were ameliorated in propofol-treated
rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6
and C-reactive protein 24 h after MCAO, which were decreased after treatment with
propofol. These results suggest that propofol protects against focal cerebral
ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol
may be a promising therapeutic agent for the treatment of ischemic stroke and
other neurodegenerative diseases associated with microglial activation.
PMID- 24349351
TI - Bone mesenchymal stem cells contributed to the neointimal formation after
arterial injury.
AB - OBJECTIVES: Recent findings suggest that in response to repair-to-injury bone
marrow mesenchymal stem cells (BMSCs) participate in the process of angiogenesis.
It is unclear what role BMSCs play in the structure of the vessel wall. In
present study, we aimed to determine whether BMSCs had the capacity of
endothelial cells (ECs). METHODS: BMSCs were separated and cultured. FACS and RT
PCR analysis confirmed the gene expression phenotype. The capacity of migration
and adhesion and the ultrastructure of BMSCs were examined. The effect of BMSCs
transplantation on the vascular repair was investigated in a murine carotid
artery-injured model. RESULTS: BMSCs could express some markers and form the tube
like structure. The migration and adhesion capacity of BMSCs increased
significantly after stimulated. In addition, BMSCs had the intact cell junction.
In vivo the local transfer of BMSCs differentiated into neo-endothelial cells in
the injury model for carotid artery and contributed to the vascular remodeling.
CONCLUSION: These results showed that BMSCs could contribute to neointimal
formation for vascular lesion and might be associated with the differentiation
into ECs, which indicated the important therapeutic implications for vascular
diseases.
PMID- 24349352
TI - NFBD1/MDC1 is phosphorylated by PLK1 and controls G2/M transition through the
regulation of a TOPOIIalpha-mediated decatenation checkpoint.
AB - Although it has been established that nuclear factor with BRCT domain 1/ mediator
of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA
damage response, its possible contribution to the regulation of cell- cycle
progression is unclear. In the present study, we have found for the first time
that NFBD1 is phosphorylated by polo-like kinase 1 (PLK1) and has an important
role in G2/M transition. Both NFBD1 and PLK1 are co-expressed in cellular nuclei
throughout G2/M transition, and binding assays demonstrated direct interaction
between NFBD1 and PLK1. Indeed, in vitro kinase reactions revealed that the PST
domain of NFBD1 contains a potential amino acid sequence (845-DVTGEE-850)
targeted by PLK1. Furthermore, enforced expression of GFP-PST but not GFP
PST(T847A) where threonine at 847 was substituted by alanine inhibited the
phosphorylation levels of histone H3, suggesting a defect of M phase entry.
Because PLK1 has been implicated in promoting the G2/M transition, we reasoned
that overexpressed PST might serve as a pseudosubstrate for PLK1 and thus
interfere with phosphorylation of endogenous PLK1 substrates. Interestingly,
siRNA-mediated knockdown of NFBD1 resulted in early M phase entry and accelerated
M phase progression, raising the possibility that NFBD1 is a PLK1 substrate for
regulating the G2/M transition. Moreover, the constitutive active form of
PLK1(T210D) overcame the ICRF-193-induced decatenation checkpoint and inhibited
the interaction between NFBD1 and topoisomerase IIalpha, but kinase-deficient
PLK1 did not. Based on these observations, we propose that PLK1-mediated
phosphorylation of NFBD1 is involved in the regulation of G2/M transition by
recovering a decatenation checkpoint.
PMID- 24349353
TI - A systematic review and meta-analysis of antibiotic-impregnated bone cement use
in primary total hip or knee arthroplasty.
AB - BACKGROUND: Antibiotic-impregnated bone cement (AIBC) has been widely used for
the treatment of infected revision arthroplasty, but its routine use in primary
total joint arthroplasty (TJA) remains considerably controversial. With this meta
analysis of published randomized controlled trials, we intended to assess the
antimicrobial efficacy and safety of AIBC for its prophylactic use in primary
TJA. METHODS: A literature search was performed in MEDLINE, Embase, CBMdisc and
the Cochrane Library until June, 2013. The studies were divided into two sub
groups according to the type of the control group. Outcomes of interest included
postoperative infection rates, radiographic outcomes and clinical joint score.
Study quality was evaluated using the Jadad scale (five points). RESULTS: In
total, eight studies were included, with a sample size of 6,381 arthroplasties.
The overall pooled data demonstrated that, compared with the control (plain
cement or systemic antibiotic), AIBC did not reveal an advantage in decreasing
the rate of superficial infection (relative risk [RR] = 1.47; 95% CI, 1.13-1.91;
P=0.004), while there were significant differences in deep infection rate between
the AIBC and control group (RR = 0.41; 95% CI, 0.17-0.97; P=0.04). For the
analysis of gentamicin and cefuroxime subgroups, the gentamicin was superior to
the cefuroxime in reducing deep infection rate (P=0.0005 versus P= 0.10).
However, no significant differences were found in their radiographic outcomes and
clinical joint score. CONCLUSION: This meta-analysis had proven that the
prophylactic use of AIBC could lower the deep infection rate in primary TJA,
while AIBC did not show an improvement in reducing the superficial infection rate
compared with the control. More sufficiently powered studies would be required to
further evaluate the efficacy and safety of AIBC for primary TJA.
PMID- 24349354
TI - Cardiac troponin I in non- acute coronary syndrome patients with chronic kidney
disease.
AB - OBJECTIVE: The aim of this study was to assess the results of troponin I (cTnI)
in non- acute Coronary Syndrome (ACS) patients with chronic kidney disease (CKD).
We also examined the risk factors for elevated cTnI in non-ACS patients with CKD
and whether stage 5 CKD modifies the associations of elevated cTnI and the risk
factors in non-ACS patients with CKD. METHODS: A retrospective study was
performed. Logistic regression models were used. RESULTS: 293 non-ACS patients
with CKD were included in the current study. 43.34% non-ACS patients with CKD
have an elevated cTnI level and 5.12% have an elevated cTnT level in MI range. In
CKD patients without ACS and heart failure, only 26.03% (38/146) patients have an
elevated cTnT level. In adjusted analyses, age, diastolic blood pressure and
congestive heart failure is associated with an elevated cTnI level in non-ACS
patients with CKD. Congestive heart failure is associated with an elevated cTnI
level in non-ACS patients with CKD (OR 2.30, 95% CI 1.08,4.88, P=0.03). Stage 5
CKD does not modify the association of congestive heart failure and an elevated
cTnI level. CONCLUSION: 43.34% non-ACS patients with CKD and 26.03% CKD patients
without ACS and congestive heart failure have an elevated cTnI level. Congestive
heart failure is associated with an elevated cTnI level in non-ACS patients with
CKD. Stage 5 CKD does not modify the association of congestive heart failure and
an elevated cTnI level.
PMID- 24349355
TI - Serum protein signatures differentiating autoimmune pancreatitis versus
pancreatic cancer.
AB - Autoimmune pancreatitis (AIP) is defined by characteristic lymphoplasmacytic
infiltrate, ductal strictures and a pancreatic enlargement or mass that can mimic
pancreatic cancer (PaCa). The distinction between this benign disease and
pancreatic cancer can be challenging. However, an accurate diagnosis may pre-empt
the misdiagnosis of cancer, allowing the appropriate medical treatment of AIP
and, consequently, decreasing the number of unnecessary pancreatic resections.
Mass spectrometry (MS) and two-dimensional differential gel electrophoresis (2D
DIGE) have been applied to analyse serum protein alterations associated with AIP
and PaCa, and to identify protein signatures indicative of the diseases.
Patients' sera were immunodepleted from the 20 most prominent serum proteins
prior to further 2D-DIGE and image analysis. The identity of the most
discriminatory proteins detected, was performed by MS and ELISAs were applied to
confirm their expression. Serum profiling data analysis with 2D-DIGE revealed 39
protein peaks able to discriminate between AIP and PaCa. Proteins were purified
and further analysed by MALDI-TOF-MS. Peptide mass fingerprinting led to
identification of eleven proteins. Among them apolipoprotein A-I, apolipoprotein
A-II, transthyretin, and tetranectin were identified and found as 3.0-, 3.5-, 2-,
and 1.6-fold decreased in PaCa sera, respectively, whereas haptoglobin and
apolipoprotein E were found to be 3.8- and 1.6-fold elevated in PaCa sera. With
the exception of haptoglobin the ELISA results of the identified proteins
confirmed the 2D-DIGE image analysis characteristics. Integration of the
identified serum proteins as AIP markers may have considerable potential to
provide additional information for the diagnosis of AIP to choose the appropriate
treatment.
PMID- 24349356
TI - Disparities in HIV screening among pregnant women--El Salvador, 2011.
AB - OBJECTIVES: To provide an accurate estimate of antenatal HIV screening and its
determinants among pregnant women in El Salvador and help local authorities make
informed decisions for targeted interventions around mother-to-child transmission
(MTCT). METHODS: A total sample of 4,730 women aged 15-49 years were interviewed
from a random sample of 3,625 households. We collected data on antenatal care
services, including HIV screening, during last pregnancy through a pre
established questionnaire. We used a backward elimination multivariate logistic
regression model to examine the association between HIV screening and
sociodemographic and health care-related factors. RESULTS: A total of 2,929 women
were included in this analysis. About 98% of participants reported receiving
antenatal care, but only 83% of these reported being screened for HIV. Screening
was lower in geographic areas with higher HIV incidence and ranged from 69.1%
among women who were not seen by a physician during antenatal care, to 93.7%
among those who attended or completed college. Odds for screening varied also by
age, employment status, household economic expenditure, possession of health care
coverage, health care settings, and number of antenatal care visits. CONCLUSIONS:
We found disparities in HIV screening during antenatal care at the environmental,
social, demographic, and structural levels despite a high uptake of antenatal
care in El Salvador. Our findings should urge health authorities to tailor and
enhance current strategies implemented to eliminate MTCT and reduce inequities
and HIV morbidity among women in El Salvador.
PMID- 24349357
TI - The Wobbler mouse model of amyotrophic lateral sclerosis (ALS) displays
hippocampal hyperexcitability, and reduced number of interneurons, but no
presynaptic vesicle release impairments.
AB - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron
disease. It is a fatal degenerative disease, best recognized for its debilitating
neuromuscular effects. ALS however also induces cognitive impairments in as many
as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical
hyperexcitability, which has been shown to precede the onset of clinical
symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler
mouse displays cortical hyperexcitability. Here we investigated if the
neocortical aberrations of the wobbler mouse also occur in the hippocampus.
Consequently, we performed extracellular field excitatory postsynaptic potential
recordings in the CA1 region of the hippocampus on acute brain slices from
symptomatic (P45-P60) and presymptomatic (P17-P21) wobbler mice. Significant
increased excitation of hippocampal synapses was revealed by leftward shifted
input/output-curves in both symptomatic and presymptomatic wobbler mice, and
substantiated by population spike occurrence analyses, demonstrating that the
increased synaptic excitation precedes the onset of visible phenotypic symptoms
in the mouse. Synaptic facilitation tested by paired-pulse facilitation and
trains in wobbler and control mice showed no differences, suggesting the absence
of presynaptic defects. Immunohistochemical staining revealed that symptomatic
wobbler mice have a lower number of parvalbumin positive interneurons when
compared to controls and presymptomatic mice. This study reveals that the wobbler
mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the
hyperexcitability could be caused by increased excitatory synaptic transmission
and a concomitant reduced inhibition due to a decreased number of parvalbumin
positive interneurons. Thus we substantiate that wobbler brain impairments are
not confined to the motor cortex, but extend to the hippocampus. Importantly, we
have revealed more details of the early pathophysiology in asymptomatic animals,
and studies like the present may facilitate the development of novel treatment
strategies for earlier intervention in ALS patients in the future.
PMID- 24349358
TI - Male infertility workup needs additional testing of expressed prostatic secretion
and/or post-massage urine.
AB - The male factor accounts for almost 50% of infertility cases. Inflammation may
reduce semen quality via several pathways, including oxidative stress (OxS). As
male infertility routinely is assessed using semen analysis only, the possible
presence of non-leukocytospermic asymptomatic inflammatory prostatitis may be
overlooked. We compared local and systemic OxS levels in male partners of
infertile couples with different inflammation patterns in their genital tract
and/or oligospermia. Subjects (n=143) were grouped according to inflammation in
their semen, expressed prostatic secretion (EPS), and/or post-massage urine (post
M). Systemic (8-isoprostanes in urine) and local (diene conjugates and total
antioxidant capacity in seminal plasma) OxS was measured The levels of OxS
markers were significantly elevated in both severe inflammation groups-
leukocytospermic men and subjects whose inflammation was limited only to EPS
and/or post-M. Comparison between oligospermic and non-oligospermic men with
genital tract inflammation, and oligozoospermic men with or without inflammation
in the genital tract indicated that inflammation but not oligospermia status had
significant impact on the measured OxS markers. Hence, a high leukocyte count in
prostate-specific materials (EPS, post-M), even in absence of clear
leukocytopsermia, is an important source of local and systemic OxS that may be
associated with male infertility and affect general health. We suggest including
the tests for detection of inflammation of the prostate into the workup of
infertile men as was suggested in the WHO 1993 recommendation.
PMID- 24349359
TI - Is obesity a risk factor for vaccine non-responsiveness?
AB - Understanding the link between vaccine immunogenicity and efficacy is currently a
major focus in HIV research. Consequently, recent developments in the HIV-1
vaccine field have led to a closer look at immune responses to known efficacious
vaccines. We undertook a study to explore clinical predictors of vaccine efficacy
following recombinant hepatitis B (rHBV) vaccination in a cohort of HIV
uninfected, hepatitis B virus naive women living in a peri-urban setting in Cape
Town. Our aim was to define host biological risk factors associated with lack of
vaccine uptake. We found a significant association (p=0.009) between body mass
index (BMI) and lack of vaccine-specific IgG titre (<10 mIU/mL). Obese
individuals (BMI >= 30 kg/m(2)) were significantly more likely to be non
responders following 2 rHBV vaccine doses (Adjusted Odds Ratio of 8.75; p=0.043).
There was no observed association between vaccine responses and age, method of
contraception or time from vaccination to antibody measurement. These data
suggest that obesity-associated factors interfere with vaccine immunogenicity and
possible efficacy.
PMID- 24349360
TI - Assessment of health status in patients with newly diagnosed chronic obstructive
pulmonary disease.
AB - SUBJECT: Chronic obstructive pulmonary disease (COPD) is a common disease
worldwide. This study aimed to investigate the health status of patients with
newly diagnosed COPD. METHODS: A total of 45 healthy controls and 218 patients
with newly diagnosed COPD were recruited. Pulmonary function test (PFT) values,
COPD assessment test (CAT) scores, exacerbation history, and demographics were
recorded. RESULTS: Forced expiratory volume in 1 s percent (FEV1%) predicted was
significantly decreased and the CAT score was significantly increased in patients
with COPD compared with healthy controls (P <0.001). Among the COPD patients, the
most commonly reported respiratory symptoms were cough (86.7%), sputum (80.3%),
and dyspnea (45%). A total of 86.2% patients were in the moderate or severe stage
(spirometric classification) of COPD, and 71.5% were in Group C or Group D
(combined assessment). A total of 33.9% of the patients had 2 or more
exacerbations in the previous year. Nearly half of the patients (45.4%) had a
high CAT score of >= 10. Patients with a history of more exacerbations had a
higher CAT score. CONCLUSIONS: Most COPD patients were symptomatic and appeared
to have moderate to severe airflow limitation or a high risk of exacerbation
before definitely being diagnosed with COPD using the PFT.
PMID- 24349361
TI - Association between the STK15 F31I polymorphism and cancer susceptibility: a meta
analysis involving 43,626 subjects.
AB - The association between the Serine/threonine kinase 15 (STK15) F31I polymorphism
(rs2273535) and cancer susceptibility remains controversial. To further
investigate this potential relationship, we conducted a comprehensive meta
analysis of 27 published studies involving a total of 19,267 multiple cancer
cases and 24,359 controls. Our results indicate statistical evidence of an
association between the STK15 F31I polymorphism and the increased risk of overall
cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T.
In a stratified analysis by cancer type, there was an increased risk of breast
cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T,
as well as esophageal cancer in two genetic models: AA vs. TA+TT and AA vs. TA.
In a stratified analysis by ethnicity, there was a significant increase in cancer
risk among Asians, but not Caucasians, in four genetic models: AA vs. TA+TT, AA
vs. TT, AA vs. TA and A vs. T. In addition, a stratified analysis by ethnicity in
the breast cancer subgroup revealed a significant increase in cancer risk among
Asians in two genetic models: AA vs. TA+TT and AA vs. TT, as well as among
Caucasians in one genetic model: AA vs. TA. In summary, this meta-analysis
demonstrates that the STK15 F31I polymorphism may be a risk factor for cancer.
PMID- 24349362
TI - Age-related modifications to the magnitude and periodicity of neuromuscular
noise.
AB - BACKGROUND: Evaluation of task related outcomes within geriatric and fall-prone
populations is essential not only for identification of neuromuscular deficits,
but also for effective implementation of fall prevention strategies. As most
tasks and activities of daily living are performed at submaximal force levels,
restoration of muscle strength often does not produce the expected benefit in
functional capacity. However, it is known that muscular control plays a key role
in the performance of functional tasks, but it remains unclear to what degree
muscular control and the associated neuromuscular noise (NmN) is age-related,
particularly in the lower-extremities. OBJECTIVES: The aim of this study was to
determine the effects of age and fall-pathology on the magnitude as well as the
frequency of NmN during lower extremity force production. METHODS: Sixteen young
healthy adults, as well as seventy elderly women (36 healthy, 34 elderly
fallers), performed force production tests at moderate levels (15% of maximum
voluntary isometric contractions). RESULTS: Elderly fallers exhibited the highest
magnitude of NmN, while the highest frequency components of NmN tended to occur
in the healthy elderly. Young subjects exhibited significantly more power in the
low frequency ranges than either of the elderly groups, and had the lowest levels
of NmN. CONCLUSION: These data suggest increased degeneration of muscular control
through greater NmN in elderly fallers compared to healthy elderly or young
subjects. This could possibly be associated with muscle atrophy and lower levels
of motor unit synchronisation.
PMID- 24349363
TI - S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line
treatment for advanced gastric carcinoma: a meta-analysis.
AB - BACKGROUND: Although both oral fluoropyrimidines were reported effective and
safe, doubts exist about whether S-1 or capecitabine is more advantageous in
advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to
comprehensively compare the efficacy and safety of S-1-based chemotherapy versus
capecitabine-based chemotherapy as first-line treatment for AGC. METHODS:
PubMed/Medline, EmBase, Cochrane library, and China National Knowledge
Infrastructure databases were searched for articles comparing S-1-based
chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were
overall response rate (ORR), time to progression (TTP), overall survival (OS),
progression-free probability, and survival probability. Secondary outcomes were
toxicities. Fixed-effects model were used and all the results were confirmed by
random-effects model. RESULTS: Five randomized controlled trials and five cohort
studies with 821 patients were included. We found equivalent ORR (38.3% vs.
39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59),
TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI
0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62
1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival
probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI
0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent
grade 3 to 4 hematological and non-hematological toxicities were found except
hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%,
OR 0.19, 95% CI 0.06-0.56, P = 0.003). There're no significant heterogeneity and
publication bias. Cumulative analysis found stable time-dependent trend.
Consistent results stratified by study design, age, regimen, cycle, country were
observed. CONCLUSION: S-1-based chemotherapy was associated with non-inferior
antitumor efficacy and better safety profile, compared with capecitabine-based
therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC,
at least in Asia.
PMID- 24349364
TI - Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and
clinicopathologic characteristics in Taiwan.
AB - BACKGROUND: Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several
types of carcinomas and is generally considered a marker of malignancy. The
current study explored the effect of CA9 gene polymorphisms on the susceptibility
of developing urothelial cell carcinoma (UCC) and the clinicopathological status.
METHODOLOGY AND PRINCIPAL FINDINGS: A total of 442 participants, including 221
healthy people and 221 patients with UCC, were recruited for this study. Four
single-nucleotide polymorphisms (SNPs) of the CA9 gene were assessed by a real
time PCR with the TaqMan assay. After adjusting for other co-variants, the
individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk
of developing UCC than did wild-type (CC) carriers. Furthermore, UCC patients who
carried at least one A allele at rs1048638 had a higher invasive stage risk (p<
0.05) than did patients carrying the wild-type allele. Moreover, among the UCC
patients with smoker, people with at least one A allele of CA9 polymorphisms
(rs1048638) had a 4.75-fold (95% CI = 1.204-18.746) increased risk of invasive
cancer. CONCLUSION: The rs1048638 polymorphic genotypes of CA9 might contribute
to the prediction of susceptibility to and pathological development of UCC. This
is the first study to provide insight into risk factors associated with CA9
variants in carcinogenesis of UCC in Taiwan.
PMID- 24349365
TI - Symptom burden of patients with dry eye disease: a four domain analysis.
AB - PURPOSE: To determine which sensory (symptom persistence and intensity) and
reactive (activity and affective interference) domains of symptom analysis are
essential for assessing symptom burden in dry eye disease (DED) patients.
METHODS: A symptom domain tool was developed to investigate all four symptom
domains in DED. In a cross-sectional pilot study, we administered the symptom
burden tool and the Ocular Surface Disease Index (OSDI) questionnaire to 48 DED
patients. Total and domain scores from the symptom burden tool and the OSDI were
normalized to achieve comparability. Spearman correlation coefficients were
calculated to measure the relationship between domains and subscales. Agreement
between the symptom burden tool and OSDI was assessed by Bland-Altman plot.
Assigned treatments were compared by symptom burden to determine whether
treatment aggressiveness is linked to symptom intensity. RESULTS: There was high
agreement between the symptom burden tool and the OSDI. Symptom persistence had a
stronger correlation with affective interference (r = 0.62 for the symptom
burden tool and r = 0.73 for the OSDI) than activity interference (r = 0.58 for
the symptom burden tool and r = 0.60 for the OSDI). Symptom intensity correlated
weakly with affective interference (r = 0.38) and activity interference (r =
0.37) in the symptom burden tool (OSDI does not have a subscale for intensity).
In patients with equal persistence of symptoms, those having high symptom
intensity were receiving more aggressive treatment (66.7%) than those with lower
symptom intensity (33.3%). CONCLUSIONS: Persistence of symptoms correlates better
with affective interference than activity interference. Intensity of symptoms may
be important for treatment decisions.
PMID- 24349366
TI - Immediate postmastectomy breast reconstruction showed limited advantage in
patient survival after stratifying by family income.
AB - BACKGROUND: Postmastectomy breast reconstruction is widely used in breast cancer
patients for its aesthetic effect. Although several studies have casted suspicion
upon the oncological safety of immediate breast reconstruction after mastectomy,
the potential impact of different reconstruction methods on patient survival
remains unclear. PATIENTS AND METHODS: We identified 35,126 female patients
diagnosed with breast cancer from January 1, 1998 to December 31, 2002 in the
Surveillance, Epidemiology, and End Results database. Breast cancer-specific
survival (BCSS) and overall survival (OS) were compared among patients who
underwent mastectomy with or without immediate breast reconstruction (autologous
reconstruction or implant reconstruction) using Cox proportional hazard
regression models. RESULTS: In multivariate analysis unadjusted for family
income, patients undergoing immediate postmastectomy reconstruction exhibited
improved BCSS [POOLED reconstruction (any types of reconstruction): hazard ratio
(HR) = 0.87, 95% confidence interval (CI) 0.80-0.95, P = 0.001] and OS (pooled
reconstruction: HR = 0.70, 95% CI 0.65-0.75, P<0.001) compared to patients who
underwent mastectomy alone. However, after stratifying by family income, patients
receiving reconstruction showed limited advantage in BCSS and OS compared with
those undergoing mastectomy alone. When comparing between the two reconstruction
methods, no significant differences were observed in either BCSS (implant versus
autologous reconstruction: HR = 1.11, 95%CI 0.90-1.35, P = 0.330) or OS (implant
versus autologous reconstruction: HR = 1.07, 95% 0.90-1.28, P = 0.424).
CONCLUSIONS: Compared to mastectomy alone, immediate postmastectomy
reconstruction had limited advantage in survival after adjusting for confounding
factor of family income. Our findings, if validated in other large databases, may
help to illustrate the actual effect of immediate postmastectomy reconstruction
on patient survival.
PMID- 24349367
TI - Development of a high-throughput three-dimensional invasion assay for anti-cancer
drug discovery.
AB - The lack of three-dimensional (3-D) high-throughput (HT) screening assays
designed to identify anti-cancer invasion drugs is a major hurdle in reducing
cancer-related mortality, with the key challenge being assay standardization.
Presented is the development of a novel 3-D invasion assay with HT potential that
involves surrounding cell-collagen spheres within collagen to create a 3-D
environment through which cells can invade. Standardization was achieved by
designing a tooled 96-well plate to create a precisely designated location for
the cell-collagen spheres and by using dialdehyde dextran to inhibit collagen
contraction, maintaining uniform size and shape. This permits automated readout
for determination of the effect of inhibitory compounds on cancer cell invasion.
Sensitivity was demonstrated by the ability to distinguish varying levels of
invasiveness of cancer cell lines, and robustness was determined by calculating
the Z-factor. A Z-factor of 0.65 was obtained by comparing the effects of DMSO
and anti-beta1-integrin antibody, an inhibitory reagent, on the invasion of Du145
cancer cells, suggesting this novel assay is suitable for large scale drug
discovery. As proof of principle, the NCI Diversity Compound Library was screened
against human invasive cancer cells. Nine compounds exhibiting high potency and
low toxicity were identified, including DX-52-1, a compound previously reported
to inhibit cell migration, a critical determinant of cancer invasion. The results
indicate that this innovative HT platform is a simple, precise, and easy to
replicate 3-D invasion assay for anti-cancer drug discovery.
PMID- 24349368
TI - The mechanism of heterogeneous beta-lactam resistance in MRSA: key role of the
stringent stress response.
AB - All methicillin resistant S. aureus (MRSA) strains carry an acquired genetic
determinant--mecA or mecC--which encode for a low affinity penicillin binding
protein -PBP2A or PBP2A'--that can continue the catalysis of peptidoglycan
transpeptidation in the presence of high concentrations of beta-lactam
antibiotics which would inhibit the native PBPs normally involved with the
synthesis of staphylococcal cell wall peptidoglycan. In contrast to this common
genetic and biochemical mechanism carried by all MRSA strains, the level of beta
lactam antibiotic resistance shows a very wide strain to strain variation, the
mechanism of which has remained poorly understood. The overwhelming majority of
MRSA strains produce a unique--heterogeneous--phenotype in which the great
majority of the bacteria exhibit very poor resistance often close to the MIC
value of susceptible S. aureus strains. However, cultures of such heterogeneously
resistant MRSA strains also contain subpopulations of bacteria with extremely
high beta-lactam MIC values and the resistance level and frequency of the highly
resistant cells in such strain is a characteristic of the particular MRSA clone.
In the study described in this communication, we used a variety of experimental
models to understand the mechanism of heterogeneous beta-lactam resistance.
Methicillin-susceptible S. aureus (MSSA) that received the mecA determinant in
the laboratory either on a plasmid or in the form of a chromosomal SCCmec
cassette, generated heterogeneously resistant cultures and the highly resistant
subpopulations that emerged in these models had increased levels of PBP2A and
were composed of bacteria in which the stringent stress response was induced.
Each of the major heterogeneously resistant clones of MRSA clinical isolates
could be converted to express high level and homogeneous resistance if the growth
medium contained an inducer of the stringent stress response.
PMID- 24349369
TI - Effects of remifemin treatment on bone integrity and remodeling in rats with
ovariectomy-induced osteoporosis.
AB - This study aims to evaluate the effects of Remifemin (isopropanolic extract of
Cimicifuga Racemosa) on postmenopausal osteoporosis. 120 female Sprague-Dawley
rats were randomly assigned to four groups: sham surgery with vehicle,
ovariectomy with vehicle, ovariectomy with estradiol valerate, or ovariectomy
with Remifemin. Daily oral administrations of the vehicle, estradiol valerate, or
Remifemin began 2 weeks after surgery and lasted to 4, 8, or 12 weeks. Ten rats
in each group were sacrificed at each timestep with assessment of bone mineral
density, trabecular bone structure, and biomechanical parameters of the femur and
lumbar vertebra. Bone turnover markers were evaluated 12 weeks after surgery.
Both drugs prevented bone density loss in the distal end of the femur and
preserved the trabecular bone structure in both the lumbar vertebra and distal
end of the femur following ovariectomy. Both drugs protected bone stiffness at
the tested regions and reduced bone reabsorption in ovariectomized rats. The
preventive effects of Remifemin against bone-loss can rival those of estradiol
valerate if treatment duration is adequately extended. In conclusion, Remifemin
may demonstrate equivalent effects to estradiol valerate in terms of preventing
postmenopausal osteoporosis.
PMID- 24349370
TI - Global analysis of transcriptome responses and gene expression profiles to cold
stress of Jatropha curcas L.
AB - BACKGROUND: Jatropha curcas L., also called the Physic nut, is an oil-rich shrub
with multiple uses, including biodiesel production, and is currently exploited as
a renewable energy resource in many countries. Nevertheless, because of its
origin from the tropical MidAmerican zone, J. curcas confers an inherent but
undesirable characteristic (low cold resistance) that may seriously restrict its
large-scale popularization. This adaptive flaw can be genetically improved by
elucidating the mechanisms underlying plant tolerance to cold temperatures. The
newly developed Illumina HiseqTM 2000 RNA-seq and Digital Gene Expression (DGE)
are deep high-throughput approaches for gene expression analysis at the
transcriptome level, using which we carefully investigated the gene expression
profiles in response to cold stress to gain insight into the molecular mechanisms
of cold response in J. curcas. RESULTS: In total, 45,251 unigenes were obtained
by assembly of clean data generated by RNA-seq analysis of the J. curcas
transcriptome. A total of 33,363 and 912 complete or partial coding sequences
(CDSs) were determined by protein database alignments and ESTScan prediction,
respectively. Among these unigenes, more than 41.52% were involved in
approximately 128 known metabolic or signaling pathways, and 4,185 were possibly
associated with cold resistance. DGE analysis was used to assess the changes in
gene expression when exposed to cold condition (12 degrees C) for 12, 24, and 48
h. The results showed that 3,178 genes were significantly upregulated and 1,244
were downregulated under cold stress. These genes were then functionally
annotated based on the transcriptome data from RNA-seq analysis. CONCLUSIONS:
This study provides a global view of transcriptome response and gene expression
profiling of J. curcas in response to cold stress. The results can help improve
our current understanding of the mechanisms underlying plant cold resistance and
favor the screening of crucial genes for genetically enhancing cold resistance in
J. curcas.
PMID- 24349371
TI - Germ-line recombination activity of the widely used hGFAP-Cre and nestin-Cre
transgenes.
AB - Herein we demonstrate with PCR, immunodetection and reporter gene approaches that
the widely used human Glial Fibrillary Acidic Protein (hGFAP)-Cre transgene
exhibits spontaneous germ-line recombination activity in leading to deletion in
brain, heart and tail tissue with high frequency. The ectopic activity of hGFAP
Cre requires a rigorous control. We likewise observed that a second widely used
nestin-Cre transgene shows germ-line deletion. Here we describe procedures to
identify mice with germ-line recombination mediated by the hGFAP-Cre and nestin
Cre transgenes. Such control is essential to avoid pleiotropic effects due to
germ-line deletion of loxP-flanked target genes and to maintain the CNS
restricted deletion status in transgenic mouse colonies.
PMID- 24349372
TI - Effects of vitamin A on in vitro maturation of pre-pubertal mouse spermatogonial
stem cells.
AB - Testicular tissue cryopreservation is the only potential option for fertility
preservation in pre-pubertal boys exposed to gonadotoxic treatment. Completion of
spermatogenesis after in vitro maturation is one of the future uses of harvested
testicular tissue. The purpose of the current study was to evaluate the effects
of vitamin A on in vitro maturation of fresh and frozen-thawed mouse pre-pubertal
spermatogonial stem cells in an organ culture system. Pre-pubertal CD1 mouse
fresh testes were cultured for 7 (D7), 9 (D9) and 11 (D11) days using an organ
culture system. Basal medium was supplemented with different concentrations of
retinol (Re) or retinoic acid (RA) alone or in combination. Seminiferous tubule
morphology (tubule diameter, intra-tubular cell type), intra-tubular cell death
and proliferation (PCNA antibody) and testosterone level were assessed at D7, D9
and D11. Pre-pubertal mouse testicular tissue were frozen after a soaking
temperature performed at -7 degrees C, -8 degrees C or -9 degrees C and after
thawing, were cultured for 9 days, using the culture medium preserving the best
fresh tissue functionality. Retinoic acid at 10(-6)M and retinol at 3.3.10(-7)M,
as well as retinol 10(-6)M are favourable for seminiferous tubule growth,
maintenance of intra-tubular cell proliferation and germ cell differentiation of
fresh pre-pubertal mouse spermatogonia. Structural and functional integrity of
frozen-thawed testicular tissue appeared to be well-preserved after soaking
temperature at -8 degrees C, after 9 days of organotypic culture using 10(-6)M
retinol. RA and Re can control in vitro germ cell proliferation and
differentiation. Re at a concentration of 10(-6)M maintains intra-tubular cell
proliferation and the ability of spermatogonia to initiate spermatogenesis in
fresh and frozen pre-pubertal mouse testicular tissue using a soaking temperature
at -8 degrees C. Our data suggested a possible human application for in vitro
maturation of cryopreserved pre-pubertal testicular tissue.
PMID- 24349373
TI - Boost protein expression through co-expression of LEA-like peptide in Escherichia
coli.
AB - The boost protein expression has been done successfully by simple co-expression
with a late embryogenesis abundant (LEA)-like peptide in Escherichia coli.
Frequently, overexpression of a recombinant protein fails to provide an adequate
yield. In the study, we developed a simple and efficient system for
overexpressing transgenic proteins in bacteria by co-expression with an LEA-like
peptide. The design of this peptide was based on part of the primary structure of
an LEA protein that is known hydrophilic protein to suppress aggregation of other
protein molecules. In our system, the expression of the target protein was
increased remarkably by co-expression with an LEA-like peptide consisting of only
11 amino acid residues. This could provide a practical method for producing
recombinant proteins efficiently.
PMID- 24349375
TI - Evidence of a high density population of harvested leopards in a montane
environment.
AB - Populations of large carnivores can persist in mountainous environments following
extensive land use change and the conversion of suitable habitat for agriculture
and human habitation in lower lying areas of their range. The significance of
these populations is poorly understood, however, and little attention has
focussed on why certain mountainous areas can hold high densities of large
carnivores and what the conservation implications of such populations might be.
Here we use the leopard (Panthera pardus) population in the western Soutpansberg
Mountains, South Africa, as a model system and show that montane habitats can
support high numbers of leopards. Spatially explicit capture-recapture (SECR)
analysis recorded the highest density of leopards reported outside of state
protected areas in sub-Saharan Africa. This density represents a temporally high
local abundance of leopards and we explore the explanations for this alongside
some of the potential conservation implications.
PMID- 24349374
TI - Mipu1, a novel direct target gene, is involved in hypoxia inducible factor 1
mediated cytoprotection.
AB - Mipu1 (myocardial ischemic preconditioning up-regulated protein 1), recently
identified in our lab, is a novel zinc-finger transcription factor which is up
regulated during ischemic preconditioning. However, it is not clear what
transcription factor contributes to its inducible expression. In the present
study, we reported that HIF-1 regulates the inducible expression of Mipu1 which
is involved in the cytoprotection of HIF-1alpha against oxidative stress by
inhibiting Bax expression. Our results showed that the inducible expression of
Mipu1 was associated with the expression and activation of transcription factor
HIF-1 as indicated by cobalt chloride (CoCl2) treatment, HIF-1alpha
overexpression and knockdown assays. EMSA and luciferase reporter gene assays
showed that HIF-1alpha bound to the hypoxia response element (HRE) within Mipu1
promoter region and promoted its transcription. Moreover, our results revealed
that Mipu1 inhibited the expression of Bax, an important pro-apoptosis protein
associated with the intrinsic pathway of apoptosis, elevating the cytoprotection
of HIF-1 against hydrogen peroxide (H2O2)-mediated injury in H9C2 cells. Our
findings implied that Bax may be a potential target gene of transcription factor
Mipu1, and provided a novel insight for understanding the cytoprotection of HIF-1
and new clues for further elucidating the mechanisms by which Mipu1 protects cell
against pathological stress.
PMID- 24349376
TI - Prognostic value of discs large homolog 7 transcript levels in prostate cancer.
AB - Hypoxia has been associated with malignant progression, metastasis and resistance
to therapy. Hence, we studied expression of hypoxia-regulated genes in 100
prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24
transcripts significantly overexpressed (p <= 0.02). Importantly, higher
transcript levels of disc large (drosophila) homolog-associated protein 5
(DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP),
hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were
associated with higher Gleason score and more advanced systemic progression.
Since the products of HMMR and CCNB1 have been identified recently as molecular
markers of CaP progression, we postulated that DLG7 has prognostic value too. To
test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case
control cohort. The cases (progression to systemic disease within six years of
surgery) and controls (no progression within eight years) were matched for
clinical and pathologic prognostic variables, including grade, stage, and
preoperative serum levels of PSA. The overall prognostic ability of DLG7, as
tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to
0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled
gene, holds prognostic potential in high-risk CaP; this also demonstrates that
variation of oxygen tension may constitute a tool for identification of novel
biomarkers for CaP.
PMID- 24349378
TI - How a hat may affect 3-month-olds' recognition of a face: an eye-tracking study.
AB - Recent studies have shown that infants' face recognition rests on a robust face
representation that is resilient to a variety of facial transformations such as
rotations in depth, motion, occlusion or deprivation of inner/outer features.
Here, we investigated whether 3-month-old infants' ability to represent the
invariant aspects of a face is affected by the presence of an external add-on
element, i.e. a hat. Using a visual habituation task, three experiments were
carried out in which face recognition was investigated by manipulating the
presence/absence of a hat during face encoding (i.e. habituation phase) and face
recognition (i.e. test phase). An eye-tracker system was used to record the time
infants spent looking at face-relevant information compared to the hat. The
results showed that infants' face recognition was not affected by the presence of
the external element when the type of the hat did not vary between the
habituation and test phases, and when both the novel and the familiar face wore
the same hat during the test phase (Experiment 1). Infants' ability to recognize
the invariant aspects of a face was preserved also when the hat was absent in the
habituation phase and the same hat was shown only during the test phase
(Experiment 2). Conversely, when the novel face identity competed with a novel
hat, the hat triggered the infants' attention, interfering with the recognition
process and preventing the infants' preference for the novel face during the test
phase (Experiment 3). Findings from the current study shed light on how faces and
objects are processed when they are simultaneously presented in the same visual
scene, contributing to an understanding of how infants respond to the multiple
and composite information available in their surrounding environment.
PMID- 24349377
TI - Generation of human induced pluripotent stem cells using epigenetic regulators
reveals a germ cell-like identity in partially reprogrammed colonies.
AB - Previous studies have shown that induced pluripotent stem cells (iPSCs) can be
derived from fibroblasts by ectopic expression of four transcription factors,
OCT4, SOX2, KLF4 and c-MYC using various methods. More recent studies have
focused on identifying alternative approaches and factors that can be used to
increase reprogramming efficiency of fibroblasts to pluripotency. Here, we use
nucleofection, morpholino technologies and novel epigenetic factors, which were
chosen based on their expression profile in human embryos, fibroblasts and
undifferentiated/differentiated human embryonic stem cells (hESCs) and
conventionally generated iPSCs, to reprogram human fibroblasts into iPSCs. By
over expressing DNMT3B, AURKB, PRMT5 and/or silencing SETD7 in human fibroblasts
with and without NANOG, hTERT and/or SV40 overexpression, we observed the
formation of colonies resembling iPSCs that were positive for certain
pluripotency markers, but exhibited minimal proliferation. More importantly, we
also demonstrate that these partially-reprogrammed colonies express high levels
of early to mid germ cell-specific genes regardless of the transfection approach,
which suggests conversion to a germ cell-like identity is associated with early
reprogramming. These findings may provide an additional means to evaluate human
germ cell differentiation in vitro, particularly in the context of pluripotent
stem cell-derived germ cell development, and contribute to our understanding of
the epigenetic requirements of the reprogramming process.
PMID- 24349379
TI - Steps to take to enhance gait stability: the effect of stride frequency, stride
length, and walking speed on local dynamic stability and margins of stability.
AB - The purpose of the current study was to investigate whether adaptations of stride
length, stride frequency, and walking speed, independently influence local
dynamic stability and the size of the medio-lateral and backward margins of
stability during walking. Nine healthy subjects walked 25 trials on a treadmill
at different combinations of stride frequency, stride length, and consequently at
different walking speeds. Visual feedback about the required and the actual
combination of stride frequency and stride length was given during the trials.
Generalized Estimating Equations were used to investigate the independent
contribution of stride length, stride frequency, and walking speed on the
measures of gait stability. Increasing stride frequency was found to enhance
medio-lateral margins of stability. Backward margins of stability became larger
as stride length decreased or walking speed increased. For local dynamic
stability no significant effects of stride frequency, stride length or walking
speed were found. We conclude that adaptations in stride frequency, stride length
and/or walking speed can result in an increase of the medio-lateral and backward
margins of stability, while these adaptations do not seem to affect local dynamic
stability. Gait training focusing on the observed stepping strategies to enhance
margins of stability might be a useful contribution to programs aimed at fall
prevention.
PMID- 24349380
TI - Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic
leukemia.
AB - The tumor microenvironment is emerging as an important therapeutic target. Most
studies, however, are focused on the protein components, and relatively little is
known of how the microenvironmental metabolome might influence tumor survival. In
this study, we examined the metabolic profiles of paired bone marrow (BM) and
peripheral blood (PB) samples from 10 children with acute lymphoblastic leukemia
(ALL). BM and PB samples from the same patient were collected at the time of
diagnosis and after 29 days of induction therapy, at which point all patients
were in remission. We employed two analytical platforms, high-resolution magnetic
resonance spectroscopy and gas chromatography-mass spectrometry, to identify and
quantify 102 metabolites in the BM and PB. Standard ALL therapy, which includes l
asparaginase, completely removed circulating asparagine, but not glutamine.
Statistical analyses of metabolite correlations and network reconstructions
showed that the untreated BM microenvironment was characterized by a significant
network-level signature: a cluster of highly correlated lipids and metabolites
involved in lipid metabolism (p<0.006). In contrast, the strongest correlations
in the BM upon remission were observed among amino acid metabolites and
derivatives (p<9.2 * 10(-10)). This study provides evidence that metabolic
characterization of the cancer niche could generate new hypotheses for the
development of cancer therapies.
PMID- 24349381
TI - Hypoxia regulates the expression of the neuromedin B receptor through a mechanism
dependent on hypoxia-inducible factor-1alpha.
AB - The neuromedin B receptor (NMB-R), a member of the mammalian bombesin receptor
family, is frequently overexpressed in various tumors. In the present study, we
found that exposure to hypoxic conditions increases the levels of NMBR mRNA and
protein in breast cancer cells, which are tightly regulated by hypoxia-inducible
factor-1alpha (HIF-1alpha). We confirmed the effect of HIF-1alpha on NMBR
transcription by performing an NMBR promoter-driven reporter assay and then
identified a functional hypoxia-responsive element (HRE) in the human NMBR
promoter region. Further, the binding of HIF-1alpha to the NMBR promoter was
corroborated by electrophoretic mobility shift and chromatin immunoprecipitation
assays, which showed that HIF-1alpha specifically and directly bound to the NMBR
promoter in response to hypoxia. Immunohistochemical analysis of a xenograft and
a human breast cancer tissue array revealed a significant correlation between NMB
R and HIF-1alpha expression. Taken together, our findings indicate that hypoxia
induces NMB-R expression through a novel mechanism to regulate HIF-1alpha
expression in breast cancer cells.
PMID- 24349382
TI - Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict
poor prognosis of soft tissue sarcomas.
AB - Recently, the possibility of PD1 pathway-targeted therapy has been extensively
studied in various human malignant tumors. However, no previous study has
investigated their potential application for soft-tissue sarcomas (STS). In this
study, we evaluated the clinical impact of intra-tumoral infiltration of PD1
positive lymphocytes and PD-L1 expression in tumor cells in 105 cases of STS.
Intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression were
seen in 65% and 58% of STS, respectively. Both PD1-positivity and PD-L1
expression were significantly associated with advanced clinicopathological
parameters such as higher clinical stage, presence of distant metastasis, higher
histological grade, poor differentiation of tumor, and tumor necrosis. Moreover,
both PD1-positivity and PD-L1 positivity were independent prognostic indicators
of overall survival (OS) and event-free survival (EFS) of STS by multivariate
analysis. In addition, the combined pattern of PD1- and PD-L1-positivity was also
an independent prognostic indicator for OS and EFS by multivariate analysis. The
patents with a PD1(+)/PD-L1(+) pattern had the shortest survival time. In
conclusion, this study is the first to demonstrate that the infiltration of PD1
positive lymphocytes and PD-L1 expression in STS cells could be used as novel
prognostic indicators for STS. Moreover, the evaluation of PD1- and PD-L1
positivity in STS is also available as possible criteria for selection of
patients suitable for PD1-based immunotherapy.
PMID- 24349383
TI - Mycobacterium avium infection induces H-ferritin expression in mouse primary
macrophages by activating Toll-like receptor 2.
AB - Important for both host and pathogen survivals, iron is a key factor in
determining the outcome of an infectious process. Iron with-holding, including
sequestration inside tissue macrophages, is considered an important strategy to
fight infection. However, for intra-macrophagic pathogens, such as Mycobacterium
avium, host defence may depend on intracellular iron sequestration mechanisms.
Ferritin, the major intracellular iron storage protein, plays a critical role in
this process. In the current study, we studied ferritin expression in mouse bone
marrow-derived macrophages upon infection with M. avium. We found that H-ferritin
is selectively increased in infected macrophages, through an up-regulation of
gene transcription. This increase was mediated by the engagement of Toll like
receptor-2, and was independent of TNF-alpha or nitric oxide production. The
formation of H-rich ferritin proteins and the consequent iron sequestration may
be an important part of the panoply of antimicrobial mechanisms of macrophages.
PMID- 24349384
TI - Protein transfection study using multicellular tumor spheroids of human hepatoma
Huh-7 cells.
AB - Several protein transfection reagents are commercially available and are powerful
tools for elucidating function of a protein in a cell. Here we described protein
transfection studies of the commercially available reagents, Pro-DeliverIN,
Xfect, and TuboFect, using Huh-7 multicellular tumor spheroid (MCTS) as a three
dimensional in vitro tumor model. A cellular uptake study using specific
endocytosis inhibitors revealed that each reagent was internalized into Huh-7
MCTS by different mechanisms, which were the same as monolayer cultured Huh-7
cells. A certain amount of Pro-DeliverIN and Xfect was uptaken by Huh-7 cells
through caveolae-mediated endocytosis, which may lead to transcytosis through the
surface-first layered cells of MCTS. The results presented here will help in the
choice and use of protein transfection reagents for evaluating anti-tumor
therapeutic proteins against MCTS models.
PMID- 24349385
TI - Eating behaviour among multi-ethnic adolescents in a middle-income country as
measured by the self-reported Children's Eating Behaviour Questionnaire.
AB - BACKGROUND: Escalating weight gain among the Malaysian paediatric population
necessitates identifying modifiable behaviours in the obesity pathway.
OBJECTIVES: This study describes the adaptation and validation of the Children's
Eating Behaviour Questionnaire (CEBQ) as a self-report for adolescents,
investigates gender and ethnic differences in eating behaviour and examines
associations between eating behaviour and body mass index (BMI) z-scores among
multi-ethnic Malaysian adolescents. METHODOLOGY: This two-phase study involved
validation of the Malay self-reported CEBQ in Phase 1 (n = 362). Principal Axis
Factoring with Promax rotation, confirmatory factor analysis and reliability
tests were performed. In Phase 2, adolescents completed the questionnaire (n =
646). Weight and height were measured. Gender and ethnic differences in eating
behaviour were investigated. Associations between eating behaviour and BMI z
scores were examined with complex samples general linear model (GLM) analyses,
adjusted for gender, ethnicity and maternal educational level. RESULTS:
Exploratory factor analysis revealed a 35-item, 9-factor structure with 'food
fussiness' scale split into two. In confirmatory factor analysis, a 30-item, 8
factor structure yielded an improved model fit. Reliability estimates of the
eight factors were acceptable. Eating behaviours did not differ between genders.
Malay adolescents reported higher Food Responsiveness, Enjoyment of Food,
Emotional Overeating, Slowness in Eating, Emotional Undereating and Food
Fussiness 1 scores (p<0.05) compared to Chinese and Indians. A significant
negative association was observed between BMI z-scores and Food Fussiness 1
('dislike towards food') when adjusted for confounders. CONCLUSION: Although CEBQ
is a valuable psychometric instrument, adjustments were required due to age and
cultural differences in our sample. With the self-report, our findings present
that gender, ethnic and weight status influenced eating behaviours. Obese
adolescents were found to display a lack of dislike towards food. Future
longitudinal and qualitative studies are warranted to further understand
behavioural phenotypes of obesity to guide prevention and intervention
strategies.
PMID- 24349386
TI - "Candidatus Similichlamydia laticola", a novel Chlamydia-like agent of
epitheliocystis in seven consecutive cohorts of farmed Australian barramundi,
Lates calcarifer (Bloch).
AB - Six consecutively hatched cohorts and one cohort of pre-hatch eggs of farmed
barramundi (Lates calcarifer) from south Australia were examined for Chlamydia
like organisms associated with epitheliocystis. To identify and characterise the
bacteria, 59 gill samples and three pre-hatch egg samples were processed for
histology, in situ hybridisation and 16S rRNA amplification, sequencing and
comprehensive phylogenetic analysis. Cases of epitheliocystis were observed
microscopically and characterised by membrane-enclosed basophilic cysts filled
with a granular material that caused hypertrophy of the epithelial cells. In situ
hybridisation with a Chlamydiales-specific probe lead to specific labelling of
the epitheliocystis inclusions within the gill epithelium. Two distinct but
closely related 16S rRNA chlamydial sequences were amplified from gill DNA across
the seven cohorts, including from pre-hatch eggs. These genotype sequences were
found to be novel, sharing 97.1 - 97.5% similarity to the next closest 16S rRNA
sequence, Ca. Similichlamydia latridicola, from Australian striped trumpeter.
Comprehensive phylogenetic analysis of these genotype sequences against
representative members of the Chlamydiales order and against other
epitheliocystis agents revealed these Chlamydia-like organisms to be novel and
taxonomically placed them within the recently proposed genus Ca. Similichlamydia.
Following Fredricks and Relman's molecular postulates and based on these
observations, we propose the epitheliocystis agents of barramundi to be known as
"Candidatus Similichlamydia laticola" (sp. nov.).
PMID- 24349387
TI - A circle-monitor for computerised assessment of visual neglect in peripersonal
space.
AB - Current assessment of visual neglect involves paper-and-pencil tests or computer
based tasks. Both have been criticised because of their lack of ecological
validity as target stimuli can only be presented in a restricted visual range.
This study examined the user-friendliness and diagnostic strength of a new
"Circle-Monitor" (CM), which enlarges the range of the peripersonal space, in
comparison to a standard paper-and-pencil test (Neglect-Test, NET). METHODS: Ten
stroke patients with neglect and ten age-matched healthy controls were examined
by the NET and the CM test comprising of four subtests (Star Cancellation, Line
Bisection, Dice Task, and Puzzle Test). RESULTS: The acceptance of the CM in
elderly controls and neglect patients was high. Participants rated the
examination by CM as clear, safe and more enjoyable than NET. Healthy controls
performed at ceiling on all subtests, without any systematic differences between
the visual fields. Both NET and CM revealed significant differences between
controls and patients in Line Bisection, Star Cancellation and visuo-constructive
tasks (NET: Figure Copying, CM: Puzzle Test). Discriminant analyses revealed
cross-validated assignment of patients and controls to groups was more precise
when based on the CM (hit rate 90%) as compared to the NET (hit rate 70%).
CONCLUSION: The CM proved to be a sensitive novel tool to diagnose visual neglect
symptoms quickly and accurately with superior diagnostic validity compared to a
standard neglect test while being well accepted by patients. Due to its
upgradable functions the system may also be a valuable tool not only to test for
non-visual neglect symptoms, but also to provide treatment and assess its
outcome.
PMID- 24349388
TI - The correlates of body composition with heart rate recovery after step test: an
exploratory study of Malaysian adolescents.
AB - BACKGROUND: In adults, heart rate recovery is a predictor of mortality, while in
adolescents it is associated with cardio-metabolic risk factors. The aim of this
study was to examine the relationship between body composition measures and heart
rate recovery (HRR) after step test in Malaysian secondary school students.
METHODS: In the Malaysian Health and Adolescents Longitudinal Research Team
(MyHEART) study, 1071 healthy secondary school students, aged 13 years old,
participated in the step test. Parameters for body composition measures were body
mass index z-score, body fat percentage, waist circumference, and waist height
ratio. The step test was conducted by using a modified Harvard step test. Heart
rate recovery of 1 minute (HRR1min) and heart rate recovery of 2 minutes
(HRR2min) were calculated by the difference between the peak pulse rate during
exercise and the resting pulse rate at 1 and 2 minutes, respectively. Analysis
was done separately based on gender. Pearson correlation analysis was used to
determine the association between the HRR parameters with body composition
measures, while multiple regression analysis was used to determine which body
composition measures was the strongest predictor for HRR. RESULTS: For both
gender groups, all body composition measures were inversely correlated with
HRR1min. In girls, all body composition measures were inversely correlated with
HRR2min, while in boys all body composition measures, except BMI z-score, were
associated with HRR2min. In multiple regression, only waist circumference was
inversely associated with HRR2min (p=0.024) in boys, while in girls it was body
fat percentage for HRR2min (p=0.008). CONCLUSION: There was an inverse
association between body composition measurements and HRR among apparently
healthy adolescents. Therefore, it is important to identify cardio-metabolic risk
factors in adolescent as an early prevention of consequent adulthood morbidity.
This reiterates the importance of healthy living which should start from young.
PMID- 24349389
TI - A randomised placebo-controlled trial to differentiate the acute cognitive and
mood effects of chlorogenic acid from decaffeinated coffee.
AB - In the current study, sixty healthy older adults aged 50 years or older, and who
were light to moderate coffee drinkers, were administered 6g of a decaffeinated
green coffee blend (NESCAFE Green Blend coffee; GB) or 540mg pure chlorogenic
acids (CGA) or placebo in a double-blind acute cross-over design, with cognitive
and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary
outcome measure was accuracy in Rapid Visual Information Processing (RVIP).
Secondary cognitive outcome measures included RVIP reaction time as well as
Inspection time (IT), Jensen Box decision/reaction times, serial subtraction and
N-Back working memory. Secondary mood measures included Bond-Lader and caffeine
Research visual analogue scales (VAS). No significant treatment effects were
found for the primary outcome measure, although significant effects were found
amongst secondary measures. Overall, CGA in isolation was not found to
significantly improve cognitive function relative to placebo whereas the GB was
found to improve sustained attention as measured by the N-Back task in comparison
to placebo overall (t=2.45,p=.05), as well as decision time on a 2-choice
reaction time task (Jensen box) in comparison to placebo at 40 minutes post-dose
(t=2.45,p=.05). Similarly, GB was found to improve alertness on both the Bond
Lader at 120 minutes relative to CGA (t=2.86, p=0.02) and the caffeine Research
VAS relative to CGA (t=3.09, p=0.009) and placebo (t=2.75,p=0.02) at 120 minutes
post-dose. Both the GB and CGA were also found to significantly improve symptoms
of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04
respectively), whilst there was a trend towards a reduction in jitteriness with
GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and
t=2.20,p=0.06 respectively). These findings suggest that the improvements in mood
observed with GB, but not the improvements in cognitive function, are likely to
some extent to be attributable to CGAs. TRIAL REGISTRATION: Australia New Zealand
Clinical Trials Registry ACTRN12611000067976 www.anzctr.org.au.
PMID- 24349390
TI - Near-infrared laser adjuvant for influenza vaccine.
AB - Safe and effective immunologic adjuvants are often essential for vaccines.
However, the choice of adjuvant for licensed vaccines is limited, especially for
those that are administered intradermally. We show that non-tissue damaging, near
infrared (NIR) laser light given in short exposures to small areas of skin,
without the use of additional chemical or biological agents, significantly
increases immune responses to intradermal influenza vaccination without
augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in
a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We
show that NIR laser treatment induces the expression of specific chemokines in
the skin resulting in recruitment and activation of dendritic cells and is safe
to use in both mice and humans. The NIR laser adjuvant technology provides a
novel, safe, low-cost, simple-to-use, potentially broadly applicable and
clinically feasible approach to enhancing vaccine efficacy as an alternative to
chemical and biological adjuvants.
PMID- 24349391
TI - Pulsed estrogen therapy prevents post-OVX porcine dura mater microvascular
network weakening via a PDGF-BB-dependent mechanism.
AB - In postmenopausal women, estrogen (E2) deficiencies are frequently associated
with higher risk of intracranial hemorrhage, increased incidence of stroke,
cerebral aneurysm, and decline in cognitive abilities. In younger postpartum
women and those using oral contraceptives, perturbations in E2 are associated
with higher risk of cerebral venous thrombosis. A number of serious intracranial
pathologic conditions linked to E2 deficiencies, such as dural sinus thrombosis,
dural fistulae, non-parenchymal intracranial hemorrhages, migraines, and
spontaneous cerebrospinal fluid leaks, involve the vessels not of the brain
itself, but of the outer fibrous membrane of the brain, the dura mater (DM). The
pathogenesis of these disorders remains mysterious and how estrogen regulates
structural and functional integrity of DM vasculature is largely unknown. Here,
we demonstrate that post ovariectomy (OVX) DM vascular remodeling is manifested
by microvessel destabilization, capillary rarefaction, increased vascular
permeability, and aberrant angio-architecture, and is the result of disrupted E2
regulated PDGF-BB signaling within dura microvasculature. These changes,
associated with the reduction in systemic PDGF-BB levels, are not corrected by a
flat-dose E2 hormone replacement therapy (HRT), but are largely prevented using
HRT schedules mimicking physiological E2 fluctuations. We demonstrate that 1) E2
regulates PDGF-BB production by endothelial cells in a dose-dependent manner and
2) optimization of PDGF-BB levels and induction of robust PDGF-mediated
endothelial cell-vascular pericyte interactions require high (estrous) E2
concentrations. We conclude that high (estrous) levels of E2 are important in
controlling PDGF-mediated crosstalk between endothelial cells and pericytes, a
fundamental mechanism governing microvessel stability and essential for
preserving intracranial homeostasis.
PMID- 24349393
TI - Clinical characteristics with an impact on ADL functions of PD patients with
cognitive impairment indicative of dementia.
AB - BACKGROUND: Dementia in Parkinson's disease (PD) is defined as cognitive decline
severe enough to affect activities of daily living function (ADL). The aim of our
exploratory study was to compare two groups of PD patients. Both groups had
cognitive deficits severe enough to justify diagnosis of dementia, but they
differed according to caregivers' rating on ADL dysfunction. Parameters which
differed between the two groups were interpreted to affect the caregivers'
perception of ADL dysfunction in PD patients with cognitive impairment indicative
of Parkinson's disease dementia. METHODOLOGY/PRINCIPAL FINDINGS: Thirty of 131
Parkinson's disease patients fulfilled the Movement Disorders Society Task Force
recommended, cognitive Level-I-criteria for dementia. According to standardized
caregiver ratings, volunteers were grouped into 18 patients with (ADL-) and 12
without instrumental activities of daily living dysfunction (ADL+). Caregiver
activities of daily living function ratings closely correlated with self
estimates of patients and those of physician (p<0.001). ADL- patients performed
worse on tests assessing visual-construction (p<0.05) and attention (p=0.03) than
ADL+ patients. Moreover, the postural instability and gait disorder subtype was
more frequent in ADL- patients (p=0.009). ADL- patients tended to have more
communication problems (p=0.05), more anxiety (p=0.05) and showed a tendency to
be treated more often with neuroleptics (p=0.049) than ADL+.
CONCLUSIONS/SIGNIFICANCE: Results indicate that worse attention, visual
construction abilities, the postural instability and gait disorder subtype,
communication problems, medication and presence of anxiety are related to
activities of daily living dysfunctions in Parkinson's disease patients with
cognitive decline indicative of dementia. Our data suggests that not only
cognitive factors but also non-cognitive factors seem to be linked to the
diagnosis of Parkinson's disease dementia associated with significant impact on
instrumental activities of daily living function. Further studies with larger
sample sizes are needed to verify our results.
PMID- 24349392
TI - An adaptive physical activity intervention for overweight adults: a randomized
controlled trial.
AB - BACKGROUND: Physical activity (PA) interventions typically include components or
doses that are static across participants. Adaptive interventions are dynamic;
components or doses change in response to short-term variations in participant's
performance. Emerging theory and technologies make adaptive goal setting and
feedback interventions feasible. OBJECTIVE: To test an adaptive intervention for
PA based on Operant and Behavior Economic principles and a percentile-based
algorithm. The adaptive intervention was hypothesized to result in greater
increases in steps per day than the static intervention. METHODS: Participants (N
= 20) were randomized to one of two 6-month treatments: 1) static intervention
(SI) or 2) adaptive intervention (AI). Inactive overweight adults (85% women, M =
36.9 +/- 9.2 years, 35% non-white) in both groups received a pedometer, email and
text message communication, brief health information, and biweekly motivational
prompts. The AI group received daily step goals that adjusted up and down based
on the percentile-rank algorithm and micro-incentives for goal attainment. This
algorithm adjusted goals based on a moving window; an approach that responded to
each individual's performance and ensured goals were always challenging but
within participants' abilities. The SI group received a static 10,000 steps/day
goal with incentives linked to uploading the pedometer's data. RESULTS: A random
effects repeated-measures model accounted for 180 repeated measures and
autocorrelation. After adjusting for covariates, the treatment phase showed
greater steps/day relative to the baseline phase (p<.001) and a group by study
phase interaction was observed (p .017). The SI group increased by 1,598
steps/day on average between baseline and treatment while the AI group increased
by 2,728 steps/day on average between baseline and treatment; a significant
between-group difference of 1,130 steps/day (Cohen's d = .74). CONCLUSIONS: The
adaptive intervention outperformed the static intervention for increasing PA. The
adaptive goal and feedback algorithm is a "behavior change technology" that could
be incorporated into mHealth technologies and scaled to reach large populations.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01793064.
PMID- 24349394
TI - Genetic diversity and population genetic structure analysis of Echinococcus
granulosus sensu stricto complex based on mitochondrial DNA signature.
AB - The genetic diversity and population genetics of the Echinococcus granulosus
sensu stricto complex were investigated based on sequencing of mitochondrial DNA
(mtDNA). Total 81 isolates of hydatid cyst collected from ungulate animals from
different geographical areas of North India were identified by sequencing of
cytochrome c oxidase subunit1 (coxi) gene. Three genotypes belonging to E.
granulosus sensu stricto complex were identified (G1, G2 and G3 genotypes).
Further the nucleotide sequences (retrieved from GenBank) for the coxi gene from
seven populations of E. granulosus sensu stricto complex covering 6 continents,
were compared with sequences of isolates analysed in this study. Molecular
diversity indices represent overall high mitochondrial DNA diversity for these
populations, but low nucleotide diversity between haplotypes. The neutrality
tests were used to analyze signatures of historical demographic events. The
Tajima's D test and Fu's FS test showed negative value, indicating deviations
from neutrality and both suggested recent population expansion for the
populations. Pairwise fixation index was significant for pairwise comparison of
different populations (except between South America and East Asia, Middle East
and Europe, South America and Europe, Africa and Australia), indicating genetic
differentiation among populations. Based on the findings of the present study and
those from earlier studies, we hypothesize that demographic expansion occurred in
E. granulosus after the introduction of founder haplotype particular by
anthropogenic movements.
PMID- 24349395
TI - In vivo characterization of dynein-driven nanovectors using Drosophila oocytes.
AB - Molecular motors transport various cargoes including vesicles, proteins and
mRNAs, to distinct intracellular compartments. A significant challenge in the
field of nanotechnology is to improve drug nuclear delivery by engineering
nanocarriers transported by cytoskeletal motors. However, suitable in vivo models
to assay transport and delivery efficiency remain very limited. Here, we develop
a fast and genetically tractable assay to test the efficiency and dynamics of
fluospheres (FS) using microinjection into Drosophila oocytes coupled with time
lapse microscopy. We designed dynein motor driven FS using a collection of dynein
light chain 8 (LC8) peptide binding motifs as molecular linkers and characterized
in real time the efficiency of the FS movement according to its linker's
sequence. Results show that the conserved LC8 binding motif allows fast
perinuclear nanoparticle's accumulation in a microtubule and dynein dependent
mechanism. These data reveal the Drosophila oocyte as a new valuable tool for the
design of motor driven nanovectors.
PMID- 24349396
TI - A low serum bicarbonate concentration as a risk factor for mortality in
peritoneal dialysis patients.
AB - BACKGROUND AND AIM: Metabolic acidosis is common in patients with chronic kidney
disease and is associated with increased mortality in hemodialysis patients.
However, this relationship has not yet been determined in peritoneal dialysis
(PD) patients. METHODS: This prospective observational study included a total of
441 incident patients who started PD between January 2000 and December 2005.
Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate
whether a low serum bicarbonate concentration can predict mortality in these
patients. RESULTS: Among the baseline parameters, serum bicarbonate level was
positively associated with hemoglobin level and residual glomerular filtration
rate (GFR), while it was negatively associated with albumin, C-reactive protein
(CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR)
in a multivariable linear regression analysis. During a median follow-up of 34.8
months, 149 deaths were recorded. After adjustment for age, diabetes, coronary
artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea,
nPCR, and percentage of lean body mass, TA-Bic level was associated with a
significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI,
0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of
24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a
13.10- and 2.13-fold increased risk of death, respectively. CONCLUSIONS: This
study showed that a low serum bicarbonate concentration is an independent risk
factor for mortality in PD patients. This relationship between low bicarbonate
levels and adverse outcome could be related to enhanced inflammation and a more
rapid loss of RRF associated with metabolic acidosis. Large randomized clinical
trials to correct acidosis are warranted to confirm our findings.
PMID- 24349397
TI - Appraisal tools for clinical practice guidelines: a systematic review.
AB - INTRODUCTION: Clinical practice guidelines can improve healthcare processes and
patient outcomes, but are often of low quality. Guideline appraisal tools aim to
help potential guideline users in assessing guideline quality. We conducted a
systematic review of publications describing guideline appraisal tools in order
to identify and compare existing tools. METHODS: Among others we searched
MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from 1995 to May
2011 for relevant primary and secondary publications. We also handsearched the
reference lists of relevant publications. On the basis of the available
literature we firstly generated 34 items to be used in the comparison of
appraisal tools and grouped them into thirteen quality dimensions. We then
extracted formal characteristics as well as questions and statements of the
appraisal tools and assigned them to the items. RESULTS: We identified 40
different appraisal tools. They covered between three and thirteen of the
thirteen possible quality dimensions and between three and 29 of the possible 34
items. The main focus of the appraisal tools were the quality dimensions
"evaluation of evidence" (mentioned in 35 tools; 88%), "presentation of guideline
content" (34 tools; 85%), "transferability" (33 tools; 83%), "independence" (32
tools; 80%), "scope" (30 tools; 75%), and "information retrieval" (29 tools;
73%). The quality dimensions "consideration of different perspectives" and
"dissemination, implementation and evaluation of the guideline" were covered by
only twenty (50%) and eighteen tools (45%) respectively. CONCLUSIONS: Most
guideline appraisal tools assess whether the literature search and the
evaluation, synthesis and presentation of the evidence in guidelines follow the
principles of evidence-based medicine. Although conflicts of interest and norms
and values of guideline developers, as well as patient involvement, affect the
trustworthiness of guidelines, they are currently insufficiently considered.
Greater focus should be placed on these issues in the further development of
guideline appraisal tools.
PMID- 24349398
TI - Diversification of two lineages of symbiotic Photobacterium.
AB - Understanding of processes driving bacterial speciation requires examination of
closely related, recently diversified lineages. To gain an insight into
diversification of bacteria, we conducted comparative genomic analysis of two
lineages of bioluminescent symbionts, Photobacterium leiognathi and 'P.
mandapamensis'. The two lineages are evolutionary and ecologically closely
related. Based on the methods used in bacterial taxonomy for classification of
new species (DNA-DNA hybridization and ANI), genetic relatedness of the two
lineages is at a cut-off point for species delineation. In this study, we
obtained the whole genome sequence of a representative P. leiognathi strain
lrivu.4.1, and compared it to the whole genome sequence of 'P. mandapamensis'
svers.1.1. Results of the comparative genomic analysis suggest that P. leiognathi
has a more plastic genome and acquired genes horizontally more frequently than
'P. mandapamensis'. We predict that different rates of recombination and gene
acquisition contributed to diversification of the two lineages. Analysis of
lineage-specific sequences in 25 strains of P. leiognathi and 'P. mandapamensis'
found no evidence that bioluminescent symbioses with specific host animals have
played a role in diversification of the two lineages.
PMID- 24349399
TI - Auditory cortex processes variation in our own speech.
AB - As we talk, we unconsciously adjust our speech to ensure it sounds the way we
intend it to sound. However, because speech production involves complex motor
planning and execution, no two utterances of the same sound will be exactly the
same. Here, we show that auditory cortex is sensitive to natural variations in
self-produced speech from utterance to utterance. We recorded event-related
potentials (ERPs) from ninety-nine subjects while they uttered "ah" and while
they listened to those speech sounds played back. Subjects' utterances were
sorted based on their formant deviations from the previous utterance. Typically,
the N1 ERP component is suppressed during talking compared to listening. By
comparing ERPs to the least and most variable utterances, we found that N1 was
less suppressed to utterances that differed greatly from their preceding
neighbors. In contrast, an utterance's difference from the median formant values
did not affect N1. Trial-to-trial pitch (f0) deviation and pitch difference from
the median similarly did not affect N1. We discuss mechanisms that may underlie
the change in N1 suppression resulting from trial-to-trial formant change.
Deviant utterances require additional auditory cortical processing, suggesting
that speaking-induced suppression mechanisms are optimally tuned for a specific
production.
PMID- 24349400
TI - Hydroxyurea could be a good clinically relevant iron chelator.
AB - Our previous study showed a reduction in serum ferritin of beta-thalassemia
patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of
hydroxyurea alone and in combination with most widely used iron chelators like
deferiprone and deferasirox for reducing iron from experimentally iron overloaded
mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The
mice were then divided into 8 groups and were orally given hydroxyurea,
deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum
ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload
and subsequently after 4 months of drug therapy. All animals were then killed.
Iron staining of the heart and liver tissue was done using Perl's Prussian Blue
stain. Dry weight of iron in the heart and liver was determined by atomic
absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight
of iron in the liver and heart showed a significant reduction in groups treated
with iron chelators with maximum reduction in the group treated with a
combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves
its role in reducing iron from iron overloaded mice. The iron chelating effect of
these drugs can also be increased if given in combination.
PMID- 24349401
TI - General anesthetics inhibit LPS-induced IL-1beta expression in glial cells.
AB - BACKGROUND: Glial cells, including microglia and astrocytes, are considered the
primary source of proinflammatory cytokines in the brain. Immune insults
stimulate glial cells to secrete proinflammatory cytokines that modulate the
acute systemic response, which includes fever, behavioral changes, and
hypothalamic-pituitary-adrenal (HPA) axis activation. We investigated the effect
of general anesthetics on proinflammatory cytokine expression in the primary
cultured glial cells, the microglial cell line BV-2, the astrocytic cell line A-1
and mouse brain. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultured glial cells
were exposed to lipopolysaccharide (LPS) in combination with general anesthetics
including isoflurane, pentobarbital, midazolam, ketamine, and propofol. Following
this treatment, we examined glial cell expression of the proinflammatory
cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF
alpha). LPS-induced expression of IL-1beta mRNA and protein were significantly
reduced by all the anesthetics tested, whereas IL-6 and TNF-alpha mRNA expression
was unaffected. The anesthetics suppressed LPS-induced extracellular signal
regulated kinase 1/2 (ERK 1/2) phosphorylation, but did not affect nuclear factor
kappaB and activator protein-1 activation. The same effect was observed with BV
2, but not with A-1 cells. In the mouse experiments, LPS was injected
intraperitoneally, and isoflurane suppressed IL-1beta in the brain and
adrenocorticotropic hormone in plasma, but not IL-1beta in plasma.
CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that general
anesthetics inhibit LPS-induced IL-1beta upregulation in glial cells,
particularly microglia, and affects HPA axis participation in the stress
response.
PMID- 24349402
TI - Risk factors for poor treatment outcomes in patients with MDR-TB and XDR-TB in
China: retrospective multi-center investigation.
AB - BACKGROUND: The treatment of patients with MDR- and XDR-TB is usually more
complex, toxic and costly and less effective than treatment of other forms of TB.
However, there is little information available on risk factors for poor outcomes
in patients with MDR- and XDR-TB in China. METHODOLOGY/PRINCIPAL FINDINGS: We
retrospectively analyzed the clinical records of HIV-negative TB Patients with
culture-proven MDR- or XDR-TB who were registered from July 2006 to June 2011 at
five large-scale Tuberculosis Specialized Hospitals in China. Among 1662 HIV
seronegative TB cases which were culture-positive for M. tuberculosis complex and
had positive sputum-smear microscopy results, 965 cases (58.1%) were DR-TB, and
586 cases (35.3%) were classified as having MDR-TB, accounting for 60.7% of DR
TB. 169 cases (10.2%) were XDR-TB, accounting for 17.5% of DR-TB, 28.8% of MDR
TB. The MDR-TB patients were divided into XDR-TB group (n=169) and other MDR-TB
group (non-XDR MDR-TB) (n=417). In total, 240 patients (40.95%) had treatment
success, and 346 (59.05%) had poor treatment outcomes. The treatment success rate
in other MDR-TB group was 52.2%, significantly higher than that in the XDR-TB
group (13%, P<0.001). In multivariate logistic regression analysis, poor outcomes
were associated with duration of previous anti-TB treatment of more than one year
(OR, 0.077; 95% CI, 0.011-0.499, P<0.001), a BMI less than 18.5 kg/m(2) (OR,
2.185; 95% CI, 1.372-3.478, P<0.001), XDR (OR, 13.368; 95% CI, 6.745-26.497,
P<0.001), retreatment (OR, 0.171; 95% CI, 0.093-0.314, P<0.001), diabetes (OR,
0.305; 95% CI, 0.140-0.663, P=0.003), tumor (OR, 0.095; 95% CI, 0.011-0.795,
P=0.03), decreased albumin (OR, 0.181; 95% CI, 0.118-0.295, P<0.001), cavitation
(OR, 0.175; 95% CI, 0.108-0.286, P<0.001). CONCLUSIONS/SIGNIFICANCE: The patients
with MDR-TB and XDR-TB have poor treatment outcomes in China.The presence of
extensive drug resistance, low BMI, hypoalbuminemia, comorbidity, cavitary
disease and previous anti-TB treatment are independent prognostic factors for
poor outcome in patients with MDR-TB.
PMID- 24349403
TI - Utility of sepsis biomarkers and the infection probability score to discriminate
sepsis and systemic inflammatory response syndrome in standard care patients.
AB - Physicians are regularly faced with severely ill patients at risk of developing
infections. In literature, standard care wards are often neglected, although
their patients frequently suffer from a systemic inflammatory response syndrome
(SIRS) of unknown origin. Fast identification of patients with infections is
vital, as they immediately require appropriate therapy. Further, tools with a
high negative predictive value (NPV) to exclude infection or bacteremia are
important to increase the cost effectiveness of microbiological examinations and
to avoid inappropriate antibiotic treatment. In this prospective cohort study,
2,384 patients with suspected infections were screened for suffering from two or
more SIRS criteria on standard care wards. The infection probability score (IPS)
and sepsis biomarkers with discriminatory power were assessed regarding their
capacity to identify infection or bacteremia. In this cohort finally consisting
of 298 SIRS-patients, the infection prevalence was 72%. Bacteremia was found in
25% of cases. For the prediction of infection, the IPS yielded 0.51 ROC-AUC
(30.1% sensitivity, 64.6% specificity). Among sepsis biomarkers,
lipopolysaccharide binding protein (LBP) was the best parameter with 0.63 ROC-AUC
(57.5% sensitivity, 67.1% specificity). For the prediction of bacteremia, the IPS
performed slightly better with a ROC-AUC of 0.58 (21.3% sensitivity, 65%
specificity). Procalcitonin was the best discriminator with 0.78 ROC-AUC, 86.3%
sensitivity, 59.6% specificity and 92.9% NPV. Furthermore, bilirubin and LBP (ROC
AUC: 0.65, 0.62) might also be considered as useful parameters. In summary, the
IPS and widely used infection parameters, including CRP or WBC, yielded a poor
diagnostic performance for the detection of infection or bacteremia. Additional
sepsis biomarkers do not aid in discriminating inflammation from infection. For
the prediction of bacteremia procalcitonin, and bilirubin were the most promising
parameters, which might be used as a rule for when to take blood cultures or
using nucleic acid amplification tests for microbiological diagnostics.
PMID- 24349404
TI - Association between ischemic stroke and iron-deficiency anemia: a population
based study.
AB - BACKGROUND: Very little is known about the relationship between non-sickle cell
anemia and stroke. The purpose of this study is to evaluate the association of
iron-deficiency anemia (IDA) with stroke based on a nationwide coverage database
in Taiwan. METHODS: The case-control study subjects were obtained from the
Taiwanese Longitudinal Health Insurance Database 2000. We included 51,093
subjects with stroke as cases and randomly selected 153,279 controls (3 controls
per case) in this study.Separate conditional logistic regression analyses were
used to calculate the odds ratio (OR) for having been previously diagnosed with
IDA between cases and controls.We further analyzed the association between stroke
and IDA by stroke subtype. RESULTS: Results showed that 3,685 study subjects
(1.81%) had been diagnosed with IDA prior to the index date; of those subjects,
1,268 (2.48%) were cases and 2,417 (1.58%) were controls (p<0.001). Conditional
logistic regression shows that the OR of having previously received an IDA
diagnosis among cases was 1.49 (95% CI: 1.39~1.60; p < 0.01) that of controls
after adjusting for monthly income, geographic region, hypertension, diabetes,
coronary heart disease, atrial fibrillation, heart failure, hyperlipidemia,
tobacco use disorder, and alcohol abuse/alcohol dependency syndrome. Furthermore,
the adjusted OR of prior IDA for cases with ischemic stroke was found to be 1.45
(95% CI: 1.34~1.58) compared to controls. However, we did not find any
significant relationship between IDA and subarachnoid/intracerebral hemorrhage
even adjusting for other confounding factors (OR=1.17, 95% CI=0.97~1.40).
CONCLUSION: There is a significant association between prior IDA and ischemic
stroke.
PMID- 24349405
TI - Catchment-scale conservation units identified for the threatened Yarra pygmy
perch (Nannoperca obscura) in highly modified river systems.
AB - Habitat fragmentation caused by human activities alters metapopulation dynamics
and decreases biological connectivity through reduced migration and gene flow,
leading to lowered levels of population genetic diversity and to local
extinctions. The threatened Yarra pygmy perch, Nannoperca obscura, is a poor
disperser found in small, isolated populations in wetlands and streams of
southeastern Australia. Modifications to natural flow regimes in
anthropogenically-impacted river systems have recently reduced the amount of
habitat for this species and likely further limited its opportunity to disperse.
We employed highly resolving microsatellite DNA markers to assess genetic
variation, population structure and the spatial scale that dispersal takes place
across the distribution of this freshwater fish and used this information to
identify conservation units for management. The levels of genetic variation found
for N. obscura are amongst the lowest reported for a fish species (mean
heterozygosity of 0.318 and mean allelic richness of 1.92). We identified very
strong population genetic structure, nil to little evidence of recent migration
among demes and a minimum of 11 units for conservation management, hierarchically
nested within four major genetic lineages. A combination of spatial analytical
methods revealed hierarchical genetic structure corresponding with catchment
boundaries and also demonstrated significant isolation by riverine distance. Our
findings have implications for the national recovery plan of this species by
demonstrating that N. obscura populations should be managed at a catchment level
and highlighting the need to restore habitat and avoid further alteration of the
natural hydrology.
PMID- 24349406
TI - Conversion of exogenous cholesterol into glycoalkaloids in potato shoots, using
two methods for sterol solubilisation.
AB - Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally
occurring in the potato, as well as in certain other Solanaceous plant species,
such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA
biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D)
in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled),
and analysed after three or five weeks. The labelled cholesterol and presence of
D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D
labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form
became present in both leaves and stems, although the major part was recovered as
steryl esters. Minor amounts of D-labelled SGA (alpha-solanine and alpha
chaconine) were identified in cholesterol-treated shoots, but not in blank
controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled
cholesterol in methyl-beta-cyclodextrin instead of Tween-80 increased the levels
of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was
recovered as labelled SGA in potato leaves. Both side chain and ring structure D
labels were retained in SGA, showing that the entire cholesterol molecule is
converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in
D5-labelled SGA, indicating that two hydrogen atoms were released during
formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol
did not produce any labelled SGA, indicating that cholesterol is a specific SGA
precursor. In conclusion, we have demonstrated a superior performance of methyl
beta-cyclodextrin for delivery of cholesterol in plant tissue feeding
experiments, and given firm evidence for cholesterol as a specific sterol
precursor of SGA in potato.
PMID- 24349407
TI - Recall responses to tetanus and diphtheria vaccination are frequently
insufficient in elderly persons.
AB - Demographic changes and a more active life-style in older age have contributed to
an increasing public awareness of the need for lifelong vaccination. Currently
many older persons have been vaccinated against selected pathogens during
childhood but lack regular booster immunizations. The impact of regular
vaccinations when started late in life was analyzed in an open, explorative trial
by evaluating the immune response against tetanus and diphtheria in healthy older
individuals. 252 persons aged above 60 years received a booster vaccination
against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was
recruited to receive a second booster vaccination against tetanus, diphtheria and
pertussis 5 years later. The percentage of unprotected individuals at the time of
enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite
protective antibody concentrations 4 weeks after the first vaccination in almost
all vaccinees, antibodies had again dropped below protective levels in 10%
(tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was
restored in almost all vaccinees after the second vaccination. No correlation
between tetanus- and diphtheria-specific responses was observed, and antibody
concentrations were not associated with age-related changes in the T cell
repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there
was no general biological "non-responder type." Post-vaccination antibody
concentrations depended on pre-existing plasma cells and B cell memory as
indicated by a strong positive relationship between post-vaccination antibodies
and pre-vaccination antibodies as well as antibody-secreting cells. In contrast,
antigen-specific T cell responses were not or only weakly associated with
antibody concentrations. In conclusion, our findings demonstrate that single shot
vaccinations against tetanus and/or diphtheria do not lead to long-lasting
immunity in many elderly persons despite administration at relatively short
intervals. Sufficient antigen-specific B cell memory B generated by adequate
priming and consecutive booster vaccinations and/or exposure is a prerequisite
for long-term protection. TRIAL REGISTRATION: EU Clinical Trials Register (EU
CTR); EudraCT number 2009-011742-26; www.clinicaltrialsregister.eu/ctr
search/trial/2009-011742-26/AT.
PMID- 24349408
TI - Arsenic compromises conducting airway epithelial barrier properties in primary
mouse and immortalized human cell cultures.
AB - Arsenic is a lung toxicant that can lead to respiratory illness through
inhalation and ingestion, although the most common exposure is through
contaminated drinking water. Lung effects reported from arsenic exposure include
lung cancer and obstructive lung disease, as well as reductions in lung function
and immune response. As part of their role in innate immune function, airway
epithelial cells provide a barrier that protects underlying tissue from inhaled
particulates, pathogens, and toxicants frequently found in inspired air. We
evaluated the effects of a five-day exposure to environmentally relevant levels
of arsenic {<4MUM [~300 MUg/L (ppb)] as NaAsO2} on airway epithelial barrier
function and structure. In a primary mouse tracheal epithelial (MTE) cell model
we found that both micromolar (3.9 MUM) and submicromolar (0.8 MUM) arsenic
concentrations reduced transepithelial resistance, a measure of barrier function.
Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns
of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1,
Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated
controls. To better quantify arsenic-induced changes in tight junction
transmembrane proteins we conducted arsenic exposure experiments with an
immortalized human bronchial epithelial cell line (16HBE14o-). We found that
arsenic exposure significantly increased the protein expression of Cl-4 and
occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells.
Additionally, arsenic exposure resulted in altered phosphorylation of occludin.
In summary, exposure to environmentally relevant levels of arsenic can alter both
the function and structure of airway epithelial barrier constituents. These
changes likely contribute to the observed arsenic-induced loss in basic innate
immune defense and increased infection in the airway.
PMID- 24349409
TI - Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases
contractility and results in a hypertrophic cardiomyopathy.
AB - Fibroblast growth factors (FGFs) and their receptors are highly conserved
signaling molecules that have been implicated in postnatal cardiac remodeling.
However, it is not known whether cardiomyocyte-expressed FGF receptors are
necessary or sufficient for ventricular remodeling in the adult heart. To
determine whether cardiomyocytes were competent to respond to an activated FGF
receptor, and to determine if this signal would result in the development of
hypertrophy, we engineered a doxycycline (DOX)-inducible, cardiomyocyte-specific,
constitutively active FGF receptor mouse model (alphaMHC-rtTA, TRE-caFgfr1-myc).
Echocardiographic and hemodynamic analysis indicated that acute expression of
caFGFR1 rapidly and directly increased cardiac contractility, while chronic
expression resulted in significant hypertrophy with preservation of systolic
function. Subsequent histologic analysis showed increased cardiomyocyte cross
sectional area and regions of myocyte disarray and fibrosis, classic features of
hypertrophic cardiomyopathy (HCM). Analysis of downstream pathways revealed a
lack of clear activation of classical FGF-mediated signaling pathways, but did
demonstrate a reduction in Serca2 expression and troponin I phosphorylation.
Isolated ventricular myocytes showed enhanced contractility and reduced
relaxation, an effect that was partially reversed by inhibition of actin-myosin
interactions. We conclude that adult cardiomyocytes are competent to transduce
FGF signaling and that FGF signaling is sufficient to promote increased
cardiomyocyte contractility in vitro and in vivo through enhanced intrinsic actin
myosin interactions. Long-term, FGFR overexpression results in HCM with a dynamic
outflow tract obstruction, and may serve as a unique model of HCM.
PMID- 24349410
TI - Evaluating the impact of different sequence databases on metaproteome analysis:
insights from a lab-assembled microbial mixture.
AB - Metaproteomics enables the investigation of the protein repertoire expressed by
complex microbial communities. However, to unleash its full potential,
refinements in bioinformatic approaches for data analysis are still needed. In
this context, sequence databases selection represents a major challenge. This
work assessed the impact of different databases in metaproteomic investigations
by using a mock microbial mixture including nine diverse bacterial and eukaryotic
species, which was subjected to shotgun metaproteomic analysis. Then, both the
microbial mixture and the single microorganisms were subjected to next generation
sequencing to obtain experimental metagenomic- and genomic-derived databases,
which were used along with public databases (namely, NCBI, UniProtKB/SwissProt
and UniProtKB/TrEMBL, parsed at different taxonomic levels) to analyze the
metaproteomic dataset. First, a quantitative comparison in terms of number and
overlap of peptide identifications was carried out among all databases. As a
result, only 35% of peptides were common to all database classes; moreover,
genus/species-specific databases provided up to 17% more identifications compared
to databases with generic taxonomy, while the metagenomic database enabled a
slight increment in respect to public databases. Then, database behavior in terms
of false discovery rate and peptide degeneracy was critically evaluated. Public
databases with generic taxonomy exhibited a markedly different trend compared to
the counterparts. Finally, the reliability of taxonomic attribution according to
the lowest common ancestor approach (using MEGAN and Unipept software) was
assessed. The level of misassignments varied among the different databases, and
specific thresholds based on the number of taxon-specific peptides were
established to minimize false positives. This study confirms that database
selection has a significant impact in metaproteomics, and provides critical
indications for improving depth and reliability of metaproteomic results.
Specifically, the use of iterative searches and of suitable filters for taxonomic
assignments is proposed with the aim of increasing coverage and trustworthiness
of metaproteomic data.
PMID- 24349411
TI - Comparative analysis of radiosensitizers for K-RAS mutant rectal cancers.
AB - Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these
mutations are associated with poor clinical response to chemoradiotherapy. We
aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing
radiation (IR) ("radiosensitizers") that could be incorporated into current
treatment strategies for locally advanced rectal cancers (LARCs) expressing
mutant K-RAS. We first optimized a high-throughput assay for measuring individual
and combined effects of SMIs and IR that produces similar results to the gold
standard colony formation assay. Using this screening platform and K-RAS mutant
rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for
radiosensitizing activity and then evaluated our top hits in follow-up
experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor
AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5
fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and
enhanced radiosensitization by AZD7762. This study is the first to compare
different SMIs in combination with IR for the treatment of K-RAS mutant rectal
cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in
new clinical trials for LARC.
PMID- 24349412
TI - Functional environmental screening of a metagenomic library identifies stlA; a
unique salt tolerance locus from the human gut microbiome.
AB - Functional environmental screening of metagenomic libraries is a powerful means
to identify and assign function to novel genes and their encoded proteins without
any prior sequence knowledge. In the current study we describe the identification
and subsequent analysis of a salt-tolerant clone from a human gut metagenomic
library. Following transposon mutagenesis we identified an unknown gene (stlA,
for "salt tolerance locus A") with no current known homologues in the databases.
Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA
confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed
in silico analysis was also conducted to gain additional information on the
properties of the encoded StlA protein. The stlA gene is rare when searched
against human metagenome datasets such as MetaHit and the Human Microbiome
Project and represents a novel and unique salt tolerance determinant which
appears to be found exclusively in the human gut environment.
PMID- 24349413
TI - Correlates of unintended pregnancy in Ethiopia: results from a national survey.
AB - BACKGROUND: Unintended pregnancy has been a major reproductive health challenge
in resource poor settings including Ethiopia. It has adverse consequences to the
mother, child and the health sector's resources. Understanding the extent of
unintended pregnancy and the factors associated is crucial to devise evidence
based interventions. The analysis was aimed at assessing the unintended pregnancy
prevalence rate among pregnant women and the factors predisposing to unintended
pregnancy. METHODS: This secondary data analysis was done on women's dataset from
the 2011 Ethiopian Demographic and Health Survey (DHS). A total of 1267 pregnant
women were included in the analysis. Multiple logistic regression analysis was
performed using SPSS software to identify the factors associated with unintended
pregnancy. Odds Ratio with 95% confidence interval (95% CI) was computed to
assess the association of different factors with unintended pregnancy. RESULTS:
The overall prevalence of unintended pregnancy was found to be 24%: those who
wanted it at a later time and not at all accounted for 17.1% and 6.9%,
respectively. The unintended pregnancy rate ranged from 1.5% in Afar Regional
State to 39.8% in Oromiya Regional State. Women who knew the timing of ovulation
had a 45% reduced chance of unintended pregnancy (OR (95% CI): 0.55 (0.35,
0.85)). Ever use of family planning, presence of five or more born children, and
two or more births in the past five years were associated with unintended
pregnancy (OR (95% CI): 1.79 (1.31, 2.45), 2.36 (1.01, 5.49) and 2.00 (1.12,
3.58), respectively). CONCLUSIONS: A significant proportion of the current
pregnancies were found to be unintended with significant variations among the
different regions. Women already burdened with higher fertility were suffering
from unintended pregnancy. Family planning programs need to concentrate on the
highly affected regions and target women with higher fertility to reduce the
level of unintended pregnancy at national level.
PMID- 24349414
TI - Psychoacoustic assessment to improve tinnitus diagnosis.
AB - The diagnosis of tinnitus relies on self-report. Psychoacoustic measurements of
tinnitus pitch and loudness are essential for assessing claims and discriminating
true from false ones. For this reason, the quantification of tinnitus remains a
challenging research goal. We aimed to: (1) assess the precision of a new
tinnitus likeness rating procedure with a continuous-pitch presentation method,
controlling for music training, and (2) test whether tinnitus psychoacoustic
measurements have the sensitivity and specificity required to detect people
faking tinnitus. Musicians and non-musicians with tinnitus, as well as simulated
malingerers without tinnitus, were tested. Most were retested several weeks
later. Tinnitus pitch matching was first assessed using the likeness rating
method: pure tones from 0.25 to 16 kHz were presented randomly to participants,
who had to rate the likeness of each tone to their tinnitus, and to adjust its
level from 0 to 100 dB SPL. Tinnitus pitch matching was then assessed with a
continuous-pitch method: participants had to match the pitch of their tinnitus to
an external tone by moving their finger across a touch-sensitive strip, which
generated a continuous pure tone from 0.5 to 20 kHz in 1-Hz steps. The
predominant tinnitus pitch was consistent across both methods for both musicians
and non-musicians, although musicians displayed better external tone pitch
matching abilities. Simulated malingerers rated loudness much higher than did the
other groups with a high degree of specificity (94.4%) and were unreliable in
loudness (not pitch) matching from one session to the other. Retest data showed
similar pitch matching responses for both methods for all participants. In
conclusion, tinnitus pitch and loudness reliably correspond to the tinnitus
percept, and psychoacoustic loudness matches are sensitive and specific to the
presence of tinnitus.
PMID- 24349415
TI - Recombinant IL-7/HGFbeta hybrid cytokine enhances T cell recovery in mice
following allogeneic bone marrow transplantation.
AB - T cell immunodeficiency is a major complication of bone marrow (BM)
transplantation (BMT). Therefore, approaches to enhance T cell reconstitution
after BMT are required. We have purified a hybrid cytokine, consisting of IL-7
and the beta-chain of hepatocyte growth factor (HGFbeta) (IL-7/HGFbeta), from a
unique long-term BM culture system. We have cloned and expressed the IL-7/HGFbeta
gene in which the IL-7 and HGFbeta genes are connected by a flexible linker to
generate rIL-7/HGFbeta protein. Here, we show that rIL-7/HGFbeta treatment
enhances thymopoiesis after allogeneic BMT. Although rIL-7 treatment also
enhances the number of thymocytes, rIL-7/HGFbeta hybrid cytokine was more
effective than was rIL-7 and the mechanisms by which rIL-7 and rIL-7/HGFbeta
increase the numbers of thymocytes are different. rIL-7 enhances the survival of
double negative (DN), CD4 and CD8 single positive (SP) thymocytes. In contrast,
rIL-7/HGFbeta enhances the proliferation of the DN, SP thymocytes, as well as the
survival of CD4 and CD8 double positive (DP) thymocytes. rIL-7/HGFbeta treatment
also increases the numbers of early thymocyte progenitors (ETPs) and thymic
epithelial cells (TECs). The enhanced thymic reconstitution in the rIL-7/HGFbeta
treated allogeneic BMT recipients results in increased number and functional
activities of peripheral T cells. Graft-versus-host-disease (GVHD) is not induced
in the rIL-7/HGFbeta-treated BMT mice. Therefore, rIL-7/HGFbeta may offer a new
tool for the prevention and/or treatment of T cell immunodeficiency following
BMT.
PMID- 24349416
TI - Stereoacuity with Frisby and revised FD2 stereo tests.
AB - We compared near stereoacuity, measured with the Frisby test, and distance
stereoacuity, measured with the revised Frisby-Davis (FD2) test, enabling a
comparison with the original version of the FD2. In the revised version of the
FD2 test, a white background is used instead of a backlit background. We also
examined the effect of age, gender and visual problems. We used the Frisby test
at distances ranging from 30-80 cm and FD2 at 6 m. The best possible score was 20
seconds of arc (arcsec) on the Frisby and 5 arcsec on the FD2; participants who
could not perform a test despite demonstrating understanding of it were classed
as stereonegative. We examined both the whole population recruited, and a sub
population screened so as to exclude visual problems. We analysed our results in
three age-groups: "visually developing" (36 children aged 5-10 years); "visually
mature" (300 participants aged 11-49 years) and "older" (29 participants aged 50
82). In the whole population, the median stereoacuity on the Frisby test was 25,
20 and 85 arcsec in the three age-groups. In the sub-population with no visual
problems, median Frisby stereoacuity was similar at 20, 20 and 80 arcsec
respectively. On the FD2, the medians were 10, 10, 20 arcsec for the whole
population and 7.5, 10 and 12.5 for the sub-population. Children were more likely
than adults to be stereonegative on the FD2, although none of the children were
stereonegative on the Frisby. The two tests showed fair agreement when used to
classify people into three categories of stereovision. Poor stereovision was
often associated with binocular problems such as tropia, but with many
exceptions. In line with previous studies, we found improvements in measured
stereoacuity in childhood and declines in late adulthood. The new FD2 test gives
comparable values to the original FD2.
PMID- 24349417
TI - Identifying vulnerable populations using a social determinants of health
framework: analysis of national survey data across six Asia-Pacific countries.
AB - BACKGROUND: In order to improve the health of the most vulnerable groups in
society, the WHO called for research on the multiple and inter-linking factors
shaping the social determinants of health (SDH). This paper analyses four key SDH
(social cohesion, social inclusion, social empowerment and socioeconomic
security) across six Asia-Pacific countries: Australia, Hong Kong, Japan, South
Korea, Taiwan, and Thailand. METHODS: Population surveys were undertaken using a
validated instrument in 2009-10, with sample sizes around 1000 in each country.
The four SDH were analysed using multivariate binomial logistic regression to
identify socio-demographic predictors in each country. RESULTS: Low socio
economic security was associated with low income in all six study countries and
with poor subjective health in Japan, South Korea and Thailand and with being
married or cohabiting in Australia and Hong Kong. Low social cohesion was
associated with low income in all countries and with undertaking household duties
in South Korea, Thailand and Taiwan. Low social inclusion was associated with low
income in Australia, South Korea and Taiwan and with poor subjective health in
Australia, Japan and South Korea. Older people had lower social inclusion in
Taiwan (50-59 years) and Hong Kong (retired), younger people in Japan and South
Korea (20-29 years in both countries) and younger and middle-aged people in
Australia. Low social empowerment was associated with low income in Australia,
Thailand and Taiwan, with being aged 60 years or over in Australia, Hong Kong and
South Korea, and over 50 years in Thailand. CONCLUSIONS: This paper provides
baseline measures for identifying where and how policy should be altered to
improve the SDH. Furthermore, these data can be used for future policy evaluation
to identify whether changes in policy have indeed improved the SDH, particularly
for marginalised and vulnerable populations.
PMID- 24349418
TI - The disease-specific phenotype in cardiomyocytes derived from induced pluripotent
stem cells of two long QT syndrome type 3 patients.
AB - Long QT syndromes (LQTS) are heritable diseases characterized by prolongation of
the QT interval on an electrocardiogram, which often leads to syncope and sudden
cardiac death. Here we report the generation of induced pluripotent stems (iPS)
cells from two patients with LQTS type 3 carrying a different point mutation in a
sodium channel Nav1.5 (p.V240M and p.R535Q) and functional characterization of
cardiomyocytes (CM) derived from them. The iPS cells exhibited all characteristic
properties of pluripotent stem cells, maintained the disease-specific mutation
and readily differentiated to CM. The duration of action potentials at 50% and
90% repolarization was longer in LQTS-3 CM as compared to control CM but this
difference did not reach statistical significance due to high variations among
cells. Sodium current recordings demonstrated longer time to peak and longer time
to 90% of inactivation of the Na(+) channel in the LQTS-3 CM. This hints at a
defective Na(+) channel caused by deficiency in open-state inactivation of the
Na(+) channel that is characteristic of LQTS-3. These analyses suggest that the
effect of channel mutation in the diseased CM is demonstrated in vitro and that
the iPS cell-derived CM can serve as a model system for studying the
pathophysiology of LQTS-3, toxicity testing and design of novel therapeutics.
However, further improvements in the model are still required to reduce cell-to
cell and cell line-to-cell line variability.
PMID- 24349420
TI - Elucidating emergence and transmission of multidrug-resistant tuberculosis in
treatment experienced patients by whole genome sequencing.
AB - BACKGROUND: Understanding the emergence and spread of multidrug-resistant
tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated
patients is generally attributed to the selection of drug resistant mutants
during inadequate therapy rather than transmission of a resistant strain.
Traditional genotyping methods are not sufficient to distinguish strains in
populations with a high burden of tuberculosis and it has previously been
difficult to assess the degree of transmission in these settings. We have used
whole genome analysis to investigate M. tuberculosis strains isolated from
treatment experienced patients with MDR-TB in Uganda over a period of four years.
METHODS AND FINDINGS: We used high throughput genome sequencing technology to
investigate small polymorphisms and large deletions in 51 Mycobacterium
tuberculosis samples from 41 treatment-experienced TB patients attending a TB
referral and treatment clinic in Kampala. This was a convenience sample
representing 69% of MDR-TB cases identified over the four year period. Low
polymorphism was observed in longitudinal samples from individual patients (2-15
SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three
clusters comprising a total of 8 patients were found with almost identical
genetic profiles, including mutations predictive for resistance to rifampicin and
isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug
susceptible disease were found to have acquired MDR strains, one of which shared
its genotype with an isolate from another patient in the cohort. CONCLUSIONS:
Whole genome sequence analysis identified MDR-TB strains that were shared by more
than one patient. The transmission of multidrug-resistant disease in this cohort
of retreatment patients emphasises the importance of early detection and need for
infection control. Consideration should be given to rapid testing for drug
resistance in patients undergoing treatment to monitor the emergence of
resistance and permit early intervention to avoid onward transmission.
PMID- 24349419
TI - Identification and characterisation of Simiate, a novel protein linked to the
fragile X syndrome.
AB - A strict regulation of protein expression during developmental stages and in
response to environmental signals is essential to every cell and organism. Recent
research has shown that the mammalian brain is particularly sensitive to
alterations in expression patterns of specific proteins and cognitive deficits as
well as autistic behaviours have been linked to dysregulated protein expression.
An intellectual disability characterised by changes in the expression of a
variety of proteins is the fragile X syndrome. Due to the loss of a single mRNA
binding protein, the Fragile X Mental Retardation Protein FMRP, vast
misregulation of the mRNA metabolism is taking place in the disease. Here, we
present the identification and characterisation of a novel protein named Simiate,
whose mRNA contains several FMRP recognition motifs and associates with FMRP upon
co-precipitation. Sequence analysis revealed that the protein evolved app. 1.7
billion years ago when eukaryotes developed. Applying antibodies generated
against Simiate, the protein is detected in a variety of tissues, including the
mammalian brain. On the subcellular level, Simiate localises to somata and
nuclear speckles. We show that Simiate and nuclear speckles experience specific
alterations in FMR1(-/-) mice. An antibody-based block of endogenous Simiate
revealed that the protein is essential for cell survival. These findings suggest
not only an important role for Simiate in gene transcription and/or RNA splicing,
but also provide evidence for a function of nuclear speckles in the fragile X
syndrome. Indeed, transcription and splicing are two fundamental mechanisms to
control protein expression, that underlie not only synaptic plasticity and memory
formation, but are also affected in several diseases associated with mental
disabilities.
PMID- 24349421
TI - Gathering and exploring scientific knowledge in pharmacovigilance.
AB - Pharmacovigilance plays a key role in the healthcare domain through the
assessment, monitoring and discovery of interactions amongst drugs and their
effects in the human organism. However, technological advances in this field have
been slowing down over the last decade due to miscellaneous legal, ethical and
methodological constraints. Pharmaceutical companies started to realize that
collaborative and integrative approaches boost current drug research and
development processes. Hence, new strategies are required to connect researchers,
datasets, biomedical knowledge and analysis algorithms, allowing them to fully
exploit the true value behind state-of-the-art pharmacovigilance efforts. This
manuscript introduces a new platform directed towards pharmacovigilance knowledge
providers. This system, based on a service-oriented architecture, adopts a plugin
based approach to solve fundamental pharmacovigilance software challenges. With
the wealth of collected clinical and pharmaceutical data, it is now possible to
connect knowledge providers' analysis and exploration algorithms with real data.
As a result, new strategies allow a faster identification of high-risk
interactions between marketed drugs and adverse events, and enable the automated
uncovering of scientific evidence behind them. With this architecture, the
pharmacovigilance field has a new platform to coordinate large-scale drug
evaluation efforts in a unique ecosystem, publicly available at
http://bioinformatics.ua.pt/euadr/.
PMID- 24349422
TI - HDAC inhibitors repress BARD1 isoform expression in acute myeloid leukemia cells
via activation of miR-19a and/or b.
AB - Over the past years BARD1 (BRCA1-associated RING domain 1) has been considered as
both a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor and
tumor suppressor gene mutated in breast and ovarian cancers. Despite its role as
a stable heterodimer with BRCA1, increasing evidence indicates that BARD1 also
has BRCA1-independent oncogenic functions. Here, we investigate BARD1 expression
and function in human acute myeloid leukemias and its modulation by epigenetic
mechanism(s) and microRNAs. We show that the HDACi (histone deacetylase
inhibitor) Vorinostat reduces BARD1 mRNA levels by increasing miR-19a and miR-19b
expression levels. Moreover, we identify a specific BARD1 isoform, which might
act as tumor diagnostic and prognostic markers.
PMID- 24349423
TI - A study of cytological changes in the bone marrow of patients with severe fever
with thrombocytopenia syndrome.
AB - BACKGROUND: Peripheral blood leucopenia and thrombocytopenia are the main
manifestations in severe fever with thrombocytopenia syndrome (SFTS) patients.
However, the underlying causes are poorly understood. Therefore, we aimed to
investigate cytology of bone marrow samples collected from SFTS patients.
METHODS: 10 SFTS patients were identified by typical clinical manifestations,
detection of peripheral blood leucopenia and thrombocytopenia, and nucleic acid
based detection of the newly identified bunyavirus. SFTS patients, along with 10
participants with acute aplastic anemia and 10 healthy volunteers were enrolled
in this study after written informed consent to undergo bone marrow cytological
examination. RESULTS: We observed similar bone marrow properties in SFTS patients
and healthy volunteers, significantly different from the characteristics observed
in acute aplastic anemia patients. CONCLUSION: Similarities between bone marrow
samples collected from SFTS patients and healthy volunteers suggest that
peripheral blood leucopenia and thrombocytopenia do not result from bone marrow
cell plasticity.
PMID- 24349424
TI - Genetic mapping of quantitative trait loci underlying flowering time in
chrysanthemum (Chrysanthemum morifolium).
AB - Flowering time is an important trait in chrysanthemum, but its genetic basis
remains poorly understood. An intra-specific mapping population bred from the
cross between the autumn-flowering cultivar 'Yuhualuoying' and the summer
flowering 'Aoyunhanxiao' was used to determine the number and relative effect of
QTL segregating for five measures of flowering time. From flowering time data
recorded over two consecutive seasons, 35 additive QTL were detected, each
explaining between 5.8% and 22.7% of the overall phenotypic variance. Of these,
13 were detected in both years. Nine genomic regions harboring QTL for at least
two of the five traits were identified. Ten pairs of loci epistatically
determined the flowering time, but their contribution to the overall phenotypic
variance was less than for the additive QTL. The results suggest that flowering
time in chrysanthemum is principally governed by main effect QTL but that
epistasis also contributes to the genetic architecture of the trait, and the
major QTL identified herein are useful in our ongoing efforts to streamline the
improvement of chrysanthemum via the use of molecular methodology.
PMID- 24349425
TI - Identification and validation of reference genes for qPCR detection of serum
microRNAs in colorectal adenocarcinoma patients.
AB - Serum microRNAs (miRNAs) have become a highlighted research hotspot, especially
for their great potential as a novel promising non-invasive biomarker in cancer
diagnosis. The most frequently used approach for serum miRNAs detection is
quantitative real time polymerase chain reaction (qPCR). In order to obtain
reliable qPCR data of miRNAs expression, the use of reference genes as endogenous
control is undoubtly necessary. However, no systematic evaluation and validation
of reference genes for normalizing qPCR analysis of serum miRNAs has been
reported in colorectal adenocarcinoma. We firstly profiled pooled serum of
colorectal adenocarcinoma, colorectal adenoma and healthy controls and selected a
list of 13 miRNAs as candidate reference genes. U6 snRNA (U6) and above-mentioned
13 miRNAs were included in further confirmation by qPCR. As a result, 5 miRNAs
(miR-151a-3p, miR-4446-3p, miR-221-3p, miR-93-5p and miR-3184-3p) were not
detected in all samples and 2 miRNAs (miR-197-3p and miR-26a-5p) were relatively
low with median Cq more than 35, and were excluded from further stability
analysis. Then variable stability of other 6 miRNAs (miR-103b, miR-484, miR-16
5p, miR-3615, miR-18a-3p and miR-191-5p) and U6 were evaluated using two
algorithms: geNorm and NormFinder which both identified miR-191-5p as the most
stably expressed reference gene and selected miR-191-5p and U6 as the most stable
pair of reference genes. After validating in an independent large cohorts and
selecting miR-92a-3p as target miRNA to evaluate the effect of reference gene, we
propose that combination of miR-191-5p and U6 could be used as reference genes
for serum microRNAs qPCR data in colorectal adenocarcinoma, colorectal adenoma
and healthy controls.
PMID- 24349426
TI - TheTGFB1 functional polymorphism rs1800469 and susceptibility to atrial
fibrillation in two Chinese Han populations.
AB - Transforming growth factor-beta1 (TGF-beta1) is related to the degree of atrial
fibrosis and plays critical roles in the induction and perpetuation of atrial
fibrillation (AF). To investigate the association of the common promoter
polymorphism rs1800469 in the TGF-beta1 gene (TGFB1) with the risk of AF in
Chinese Han population, we carried out a case-control study of two hospital-based
independent populations: Southeast Chinese population (581 patients with AF and
723 controls), and Northeast Chinese population (308 AF patients and 292
controls). Two hundred and seventy-eight cases of AF were lone AF and 334 cases
of AF were diagnosed as paroxysmal AF. In both populations, AF patients had
larger left atrial diameters than the controls did. The rs1800469 genotypes in
the TGFB1 gene were determined by polymerase chain reaction-restriction fragment
length polymorphism. The genotype and allele frequencies of rs1800469 were not
different between AF patients and controls of the Southeast Chinese population,
Northeast Chinese population, and total Study Population. After adjustment for
age, sex, hypertension and LAD, there was no association between the rs1800469
polymorphism and the risk of AF under the dominant, recessive and additive
genetic models. Similar results were obtained from subanalysis of the lone and
paroxymal AF subgroups. Our results do not support the role of the TGFB1
rs1800469 functional gene variant in the development of AF in the Chinese Han
population.
PMID- 24349427
TI - Mechanical ventilation drives inflammation in severe viral bronchiolitis.
AB - INTRODUCTION: Respiratory insufficiency due to severe respiratory syncytial virus
(RSV) infection is the most frequent cause of paediatric intensive care unit
admission in infants during the winter season. Previous studies have shown
increased levels of inflammatory mediators in airways of mechanically ventilated
children compared to spontaneous breathing children with viral bronchiolitis. In
this prospective observational multi-center study we aimed to investigate whether
this increase was related to disease severity or caused by mechanical
ventilation. MATERIALS AND METHODS: Nasopharyngeal aspirates were collected <1
hour before intubation and 24 hours later in RSV bronchiolitis patients with
respiratory failure (n = 18) and non-ventilated RSV bronchiolitis controls (n =
18). Concentrations of the following cytokines were measured: interleukin (IL)
1alpha, IL-1beta, IL-6, monocyte chemotactic protein (MCP)-1 and macrophage
inflammatory protein (MIP)-1alpha. RESULTS: Baseline cytokine levels were
comparable between ventilated and non-ventilated infants. After 24 hours of
mechanical ventilation mean cytokine levels, except for MIP-1alpha, were elevated
compared to non-ventilated infected controls: IL-1alpha (159 versus 4 pg/ml,
p<0.01), IL-1beta (1068 versus 99 pg/ml, p<0.01), IL-6 (2343 versus 958 pg/ml,
p<0.05) and MCP-1 (174 versus 26 pg/ml, p<0.05). CONCLUSIONS: Using pre- and post
intubation observations, this study suggests that endotracheal intubation and
subsequent mechanical ventilation cause a robust pulmonary inflammation in
infants with RSV bronchiolitis.
PMID- 24349428
TI - Characterization of amylolysin, a novel lantibiotic from Bacillus
amyloliquefaciens GA1.
AB - BACKGROUND: Lantibiotics are heat-stable peptides characterized by the presence
of thioether amino acid lanthionine and methyllanthionine. They are capable to
inhibit the growth of Gram-positive bacteria, including Listeria monocytogenes,
Staphylococcus aureus or Bacillus cereus, the causative agents of food-borne
diseases or nosocomial infections. Lantibiotic biosynthetic machinery is encoded
by gene cluster composed by a structural gene that codes for a pre-lantibiotic
peptide and other genes involved in pre-lantibiotic modifications, regulation,
export and immunity. METHODOLOGY/FINDINGS: Bacillus amyloliquefaciens GA1 was
found to produce an antimicrobial peptide, named amylolysin, active on an array
of Gram-positive bacteria, including methicillin resistant S. aureus. Genome
characterization led to the identification of a putative lantibiotic gene cluster
that comprises a structural gene (amlA) and genes involved in modification
(amlM), transport (amlT), regulation (amlKR) and immunity (amlFE). Disruption of
amlA led to loss of biological activity, confirming thus that the identified gene
cluster is related to amylolysin synthesis. MALDI-TOF and LC-MS analysis on
purified amylolysin demonstrated that this latter corresponds to a novel
lantibiotic not described to date. The ability of amylolysin to interact in vitro
with the lipid II, the carrier of peptidoglycan monomers across the cytoplasmic
membrane and the presence of a unique modification gene suggest that the
identified peptide belongs to the group B lantibiotic. Amylolysin immunity seems
to be driven by only two AmlF and AmlE proteins, which is uncommon within the
Bacillus genus. CONCLUSION/SIGNIFICANCE: Apart from mersacidin produced by
Bacillus amyloliquefaciens strains Y2 and HIL Y-85,544728, reports on the
synthesis of type B-lantibiotic in this species are scarce. This study reports on
a genetic and structural characterization of another representative of the type B
lantibiotic in B. amyloliquefaciens.
PMID- 24349429
TI - LASIK following small incision lenticule extraction (SMILE) lenticule re
implantation: a feasibility study of a novel method for treatment of presbyopia.
AB - Presbyopia remains a major visual impairment for patients, who have previously
undergone laser refractive correction and enjoyed unaided distance vision prior
to the onset of presbyopia. Corneal stromal volume restoration through small
incision lenticule extraction (SMILE) lenticule re-implantation presents an
opportunity for restoring the patients' non-dominant eye to previous low myopia
to achieve a monovision. In this study, we investigated the feasibility of
performing LASIK after lenticule re-implantation as a method to create presbyopic
monovision. A -6.00D SMILE correction was performed in 9 rabbit eyes. The
lenticules were cryopreserved for 14 days and re-implanted. Five weeks later, 3
of these eyes underwent LASIK for -5.00D correction (RL group); 3 underwent LASIK
flap creation, which was not lifted (RN); and no further procedures were
performed on the remaining 3 eyes. These groups were compared with 3 eyes that
underwent standard LASIK for a -5.00D correction (LO); 3 that underwent creation
of non-lifted flap (LN); and 3 non-operated eyes. Rabbits were euthanized 1 day
post-surgery. Tissue responses were analyzed by immunohistochemistry, slit lamp
and in vivo confocal microscopy (IVCM). Intrastromal irregularities and elevated
reflectivity levels of the excimer-ablated plane were observed on slit lamp and
IVCM, respectively in the RL group. The results were comparable (P = 0.310) to
IVCM findings in the LO group. RL and LO groups showed similar fibronectin
expression levels, number of CD11b-positive cells (P = 0.304) and apoptotic cells
(P = 0.198). There was no difference between the RN and LN groups in reflectivity
levels (P = 0.627), fibronectin expression levels, CD11b-positive cells (P =
0.135) and apoptotic cells (P = 0.128). LASIK can be performed following
lenticule re-implantation to create presbyopic monovision. The tissue responses
elicited after performing LASIK on corneas that have undergone SMILE and
subsequent lenticule re-implantation are similar to primary procedure.
PMID- 24349430
TI - Natural conditions override differences in emergence rhythm among closely related
drosophilids.
AB - Previous studies on adult emergence rhythm of Drosophila melanogaster (DM) done
under semi-natural conditions have shown that emergence is correlated to daily
changes in temperature, humidity and light at dawn. Recently we showed that under
laboratory conditions D. ananassae (DA), a closely related species of DM exhibits
patterns in its activity/rest rhythm distinct from the latter. Here, we report
the results of a study aimed at examining whether this difference in
activity/rest rhythm among species extends to other circadian behaviours such as
the adult emergence rhythm under a more natural environment with multiple cyclic
time cues. We monitored the adult emergence rhythm of recently wild-caught DM and
DA populations in parallel with those of a related species D. malerkotliana (DK),
both in the laboratory and under semi-natural conditions. We find that although
DM, DK and DA showed marked difference from one another under laboratory
conditions, such differences were not detectable in the emergence behaviour of
these three species under semi-natural conditions, and that they respond very
similarly to seasonal changes in the environment. The results suggest that
seasonal changes in temperature and humidity contribute largely to the variation
in adult emergence waveform in terms of gate width, phase and amplitude of the
peak and day-to-day variance in the timing of the emergence peak. In all three
species, seasons with cooler and wetter conditions make the rhythm less tightly
gated, with low amplitude peak and high day-to-day variation in timing of the
peak of emergence. We show that in nature the emergence rhythm of DM, DK and DA
is strongly influenced by environmental factors such that in a given season all
of them exhibit similar time course and waveform and that with the changing
season, they all modify their emergence patterns in a similar manner.
PMID- 24349431
TI - The ciliary protein cystin forms a regulatory complex with necdin to modulate Myc
expression.
AB - Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a
well-characterized mouse model of autosomal recessive polycystic kidney disease
(ARPKD). Interestingly, overexpression of the Myc gene is evident in animal
models of ARPKD and is thought to contribute to the renal cystic phenotype. Using
a yeast two-hybrid approach, the growth suppressor protein necdin, known to
modulate Myc expression, was found as an interacting partner of cystin. Deletion
mapping demonstrated that the C-terminus of cystin and both termini of necdin are
required for their mutual interaction. Speculating that these two proteins may
function to regulate gene expression, we developed a luciferase reporter assay
and observed that necdin strongly activated the Myc P1 promoter, and cystin did
so more modestly. Interestingly, the necdin effect was significantly abrogated
when cystin was co-transfected. Chromatin immunoprecipitation and electrophoretic
mobility shift assays revealed a physical interaction with both necdin and cystin
and the Myc P1 promoter, as well as between these proteins. The data suggest that
these proteins likely function in a regulatory complex. Thus, we speculate that
Myc overexpression in the cpk kidney results from the dysregulation of the cystin
necdin regulatory complex and c-Myc, in turn, contributes to cystogenesis in the
cpk mouse.
PMID- 24349432
TI - Proteomic profiling of Burkholderia cenocepacia clonal isolates with different
virulence potential retrieved from a cystic fibrosis patient during chronic lung
infection.
AB - Respiratory infections with Burkholderia cepacia complex (Bcc) bacteria in cystic
fibrosis (CF) are associated with a worse prognosis and increased risk of death.
In this work, we assessed the virulence potential of three B. cenocepacia clonal
isolates obtained from a CF patient between the onset of infection (isolate
IST439) and before death with cepacia syndrome 3.5 years later (isolate IST4113
followed by IST4134), based on their ability to invade epithelial cells and
compromise epithelial monolayer integrity. The two clonal isolates retrieved
during late-stage disease were significantly more virulent than IST439. Proteomic
profiling by 2-D DIGE of the last isolate recovered before the patient's death,
IST4134, and clonal isolate IST439, was performed and compared with a prior
analysis of IST4113 vs. IST439. The cytoplasmic and membrane-associated enriched
fractions were examined and 52 proteins were found to be similarly altered in the
two last isolates compared with IST439. These proteins are involved in metabolic
functions, nucleotide synthesis, translation and protein folding, cell envelope
biogenesis and iron homeostasis. Results are suggestive of the important role
played by metabolic reprogramming in the virulence potential and persistence of
B. cenocepacia, in particular regarding bacterial adaptation to microaerophilic
conditions. Also, the content of the virulence determinant AidA was higher in the
last 2 isolates. Significant levels of siderophores were found to be secreted by
the three clonal isolates in an iron-depleted environment, but the two late
isolates were more tolerant to low iron concentrations than IST439, consistent
with the relative abundance of proteins involved in iron uptake.
PMID- 24349433
TI - A trio of viral proteins tunes aphid-plant interactions in Arabidopsis thaliana.
AB - BACKGROUND: Virus-induced deterrence to aphid feeding is believed to promote
plant virus transmission by encouraging migration of virus-bearing insects away
from infected plants. We investigated the effects of infection by an aphid
transmitted virus, cucumber mosaic virus (CMV), on the interaction of Arabidopsis
thaliana, one of the natural hosts for CMV, with Myzus persicae (common names:
'peach-potato aphid', 'green peach aphid'). METHODOLOGY/PRINCIPAL FINDINGS:
Infection of Arabidopsis (ecotype Col-0) with CMV strain Fny (Fny-CMV) induced
biosynthesis of the aphid feeding-deterrent 4-methoxy-indol-3-yl
methylglucosinolate (4MI3M). 4MI3M inhibited phloem ingestion by aphids and
consequently discouraged aphid settling. The CMV 2b protein is a suppressor of
antiviral RNA silencing, which has previously been implicated in altering plant
aphid interactions. Its presence in infected hosts enhances the accumulation of
CMV and the other four viral proteins. Another viral gene product, the 2a protein
(an RNA-dependent RNA polymerase), triggers defensive signaling, leading to
increased 4MI3M accumulation. The 2b protein can inhibit ARGONAUTE1 (AGO1), a
host factor that both positively-regulates 4MI3M biosynthesis and negatively
regulates accumulation of substance(s) toxic to aphids. However, the 1a replicase
protein moderated 2b-mediated inhibition of AGO1, ensuring that aphids were
deterred from feeding but not poisoned. The LS strain of CMV did not induce
feeding deterrence in Arabidopsis ecotype Col-0. CONCLUSIONS/SIGNIFICANCE:
Inhibition of AGO1 by the 2b protein could act as a booby trap since this will
trigger antibiosis against aphids. However, for Fny-CMV the interplay of three
viral proteins (1a, 2a and 2b) appears to balance the need of the virus to
inhibit antiviral silencing, while inducing a mild resistance (antixenosis) that
is thought to promote transmission. The strain-specific effects of CMV on
Arabidopsis-aphid interactions, and differences between the effects of Fny-CMV on
this plant and those seen previously in tobacco (inhibition of resistance to
aphids) may have important epidemiological consequences.
PMID- 24349434
TI - Role of miR-17 family in the negative feedback loop of bone morphogenetic protein
signaling in neuron.
AB - Bone morphogenetic protein (BMP) signaling is active in many tissues including
the central nervous system, in which it regulates cell proliferation,
differentiation and maturation. The modulation of BMP pathway is crucial since
abnormality of BMP signaling may cause cellular malfunction such as apoptosis.
There are evidences indicating that miR-17 family is involved in the BMP
signaling. In the present study, we demonstrated that BMP2 stimulation directly
increased the transcription of miR-17-92 and miR-106b-25 cluster via Smad
activation, which leads to the up-regulation of mature miR-17/20a/93. In
addition, we provided evidence that BMP2 activation repressed BMPRII expression
through modulating miR-17 family in primary neurons. Furthermore, we proved that
such negative regulation protected neurons from apoptosis induced by abnormal BMP
signaling. Taken together, these results suggest a regulatory pathway of BMP-miR
17 family-BMPRII, which consist a negative feedback loop that balances BMP
signaling and maintains cell homeostasis in neurons.
PMID- 24349435
TI - Do strategies to improve quality of maternal and child health care in lower and
middle income countries lead to improved outcomes? A review of the evidence.
AB - OBJECTIVES: Efforts to scale-up maternal and child health services in lower and
middle income countries will fail if services delivered are not of good quality.
Although there is evidence of strategies to increase the quality of health
services, less is known about the way these strategies affect health system goals
and outcomes. We conducted a systematic review of the literature to examine this
relationship. METHODS: We undertook a search of MEDLINE, SCOPUS and CINAHL
databases, limiting the results to studies including strategies specifically
aimed at improving quality that also reported a measure of quality and at least
one indicator related to health system outcomes. Variation in study methodologies
prevented further quantitative analysis; instead we present a narrative review of
the evidence. FINDINGS: Methodologically, the quality of evidence was poor, and
dominated by studies of individual facilities. Studies relied heavily on service
utilisation as a measure of strategy success, which did not always correspond to
improved quality. The majority of studies targeted the competency of staff and
adequacy of facilities. No strategies addressed distribution systems, public
private partnership or equity. Key themes identified were the conflict between
perceptions of patients and clinical measures of quality and the need for
holistic approaches to health system interventions. CONCLUSION: Existing evidence
linking quality improvement strategies to improved MNCH outcomes is extremely
limited. Future research would benefit from the inclusion of more appropriate
indicators and additional focus on non-facility determinants of health service
quality such as health policy, supply distribution, community acceptability and
equity of care.
PMID- 24349436
TI - A large novel deletion downstream of PAX6 gene in a Chinese family with ocular
coloboma.
AB - PURPOSE: The paired box gene 6 (PAX6) is an essential transcription factor for
eye formation. Genetic alterations in PAX6 can lead to various ocular
malformations including aniridia. The purpose of this study was to identify
genetic defects as the underlying cause of familial ocular coloboma in a large
Chinese family. METHODS: After linkage analysis was carried out in this family,
all exons of PAX6 in the proband were sequenced by the Sanger sequencing
technique. Then the genome of the proband was evaluated by a microarray-based
comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied
to verify the abnormal aCGH findings. RESULTS: All patients presented bilateral
partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and
congenital posterior polar cataracts. Two-point linkage analysis in the autosomal
dominant family showed loss of heterozygosity at the D11S914 locus. There was no
pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb
heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified
the deletion in the patients and further confirmed this deletion cosegregation
with the ocular coloboma phenotype in the family. CONCLUSIONS: The 681 kb large
deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the
familial ocular coloboma in this large Chinese family. aCGH should be applied if
there is a negative result for the mutation detection of PAX6 in patients with
ocular coloboma.
PMID- 24349437
TI - Cell-specific cre recombinase expression allows selective ablation of glutamate
receptors from mouse horizontal cells.
AB - In the mouse retina, horizontal cells form an electrically coupled network and
provide feedback signals to photoreceptors and feedforward signals to bipolar
cells. Thereby, horizontal cells contribute to gain control at the first visual
synapse and to the antagonistic organization of bipolar and ganglion cell
receptive fields. However, the nature of horizontal cell output remains a matter
of debate, just as the exact contribution of horizontal cells to center-surround
antagonism. To facilitate studying horizontal cell function, we developed a
knockin mouse line which allows ablating genes exclusively in horizontal cells.
This knockin line expresses a Cre recombinase under the promoter of connexin57
(Cx57), a gap junction protein only expressed in horizontal cells. Consistently,
in Cx57+/Cre mice, Cre recombinase is expressed in almost all horizontal cells
(>99%) and no other retinal neurons. To test Cre activity, we crossbred Cx57+/Cre
mice with a mouse line in which exon 11 of the coding sequence for the ionotropic
glutamate receptor subunit GluA4 was flanked by two loxP sites (GluA4fl/fl). In
GluA4fl/fl:Cx57+/Cre mice, GluA4 immunoreactivity was significantly reduced (~
50%) in the outer retina where horizontal cells receive photoreceptor inputs,
confirming the functionality of the Cre/loxP system. Whole-cell patch-clamp
recordings from isolated horizontal cell somata showed a reduction of glutamate
induced inward currents by ~ 75%, suggesting that the GluA4 subunit plays a major
role in mediating photoreceptor inputs. The persistent current in GluA4-deficient
cells is mostly driven by AMPA and to a very small extent by kainate receptors as
revealed by application of the AMPA receptor antagonist GYKI52466 and
concanavalin A, a potentiator of kainate receptor-mediated currents. In summary,
the Cx57+/Cre mouse line provides a versatile tool for studying horizontal cell
function. GluA4fl/fl:Cx57+/Cre mice, in which horizontal cells receive less
excitatory input, can thus be used to analyze the contribution of horizontal
cells to retinal processing.
PMID- 24349438
TI - Lin28 induces epithelial-to-mesenchymal transition and stemness via
downregulation of let-7a in breast cancer cells.
AB - The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the
biogenesis of let-7, which functions as a tumor suppressor. However, the role of
the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and
stemness in breast cancer has not been clearly expatiated. In our previous study,
we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast
cancer stem cells. In the present study, we demonstrated that Lin28 was highly
expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was
barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28
remarkably induced the EMT, increased a higher mammosphere formation rate and
ALDH activity and subsequently promoted colony formation, as well as adhesion and
migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced
EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28
overexpression was found in breast cancers that had undergone metastasis and was
strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced
the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a
therapeutic target for the eradication of breast cancer metastasis.
PMID- 24349439
TI - Propranolol restricts the mobility of single EGF-receptors on the cell surface
before their internalization.
AB - The epidermal growth factor receptor is involved in morphogenesis, proliferation
and cell migration. Its up-regulation during tumorigenesis makes this receptor an
interesting therapeutic target. In the absence of the ligand, the inhibition of
phosphatidic acid phosphohydrolase activity by propranolol treatment leads to
internalization of empty/inactive receptors. The molecular events involved in
this endocytosis remain unknown. Here, we quantified the effects of propranolol
on the mobility of single quantum-dot labelled receptors before the actual
internalization took place. The single receptors showed a clear stop-and-go
motion; their diffusive tracks were continuously interrupted by sub-second
stalling events, presumably caused by transient clustering. In the presence of
propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates
an increase in drag of the receptor. Atomic force microscopy measurements did not
show an increase of the effective membrane tension, such that clustering of the
receptor remains the likely mechanism for its reduced mobility. ii) The receptor
got frequently stalled for longer periods of multiple seconds, which may signal
the first step of the internalization process.
PMID- 24349440
TI - Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and
implications for signaling.
AB - Zinc RING finger 3 (ZNRF3) and its homolog RING finger 43 (RNF43) antagonize Wnt
signaling in adult stem cells by ubiquitinating Frizzled receptors (FZD), which
leads to endocytosis of the Wnt receptor. Conversely, binding of ZNRF3/RNF43 to
LGR4-6 - R-spondin blocks Frizzled ubiquitination and enhances Wnt signaling.
Here, we present crystal structures of the ZNRF3 ectodomain and its complex with
R-spondin 1 (RSPO1). ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity
via RSPO1 furin-like 1 (Fu1) domain. Anonychia-related mutations in RSPO4 support
the importance of the observed interface. The ZNRF3-RSPO1 structure resembles
that of LGR5-RSPO1-RNF43, though Fu2 of RSPO1 is variably oriented. The ZNRF3
binding site overlaps with trans-interactions observed in 2:2 LGR5-RSPO1
complexes, thus binding of ZNRF3/RNF43 would disrupt such an arrangement.
Sequence conservation suggests a single ligand-binding site on ZNRF3, consistent
with the proposed competing binding role of ZNRF3/RNF43 in Wnt signaling.
PMID- 24349441
TI - Functional complementation of sir2Delta yeast mutation by the human orthologous
gene SIRT1.
AB - Sirtuins, class III histone deacetylases, are proteins homologous to the yeast
protein Sir2p. Mammalian Sirt1 has been shown to be involved in energy
metabolism, brain functions, inflammation and aging through its deacetylase
activity, acting on both histone and non-histone substrates. In order to verify
whether Sirt1 can replace Sir2p in the yeast cells, we expressed the full-length
human Sirt1 protein in S.cerevisiae sir2Delta mutant strain. The structure of
chromatin is basically maintained from yeast to human. Thus, yeast chromatin is a
favourable environment to evaluate, inhibit or activate an ectopic histone
deacetylase activity in an in vivo substrate. Mutant sir2Delta shows a series of
different phenotypes, all dependent on the deacetylase activity of Sir2p. We
analyzed the three silent loci where normally Sir2p acts: ribosomal DNA,
telomeres and the mating type loci. Moreover, we verified extrachromosomal
ribosomal DNA circles production and histone hyperacetylation levels, typical
marks of sir2Delta strains. By strong SIRT1 overexpression in sir2Delta cells, we
found that specific molecular phenotypes of the mutant revert almost to a wild
type condition. In particular, transcriptional silencing at rDNA was restored,
extrachromosomal rDNA circles formation was repressed and histone acetylation at
H3K9 and H4K16 decreased. The complementation at the other studied loci: HM loci,
telomere and sub-telomere does not occur. Overall, our observations indicate
that: i) SIRT1 gene is able to complement different molecular phenotypes of the
sir2Delta mutant at rDNA ii) the in vivo screening of Sirt1 activity is possible
in yeast.
PMID- 24349442
TI - A trifluoromethyl analogue of celecoxib exerts beneficial effects in
neuroinflammation.
AB - Celecoxib is a selective cyclooxygenase-2 (COX2) inhibitor. We have previously
shown that celecoxib inhibits experimental autoimmune encephalomyelitis (EAE) in
COX-2-deficient mice, suggestive for a mode of action involving COX2-independent
pathways. In the present study, we tested the effect of a trifluoromethyl
analogue of celecoxib (TFM-C) with 205-fold lower COX-2 inhibitory activity in
two models of neuroinflammation, i.e. cerebellar organotypic cultures challenged
with LPS and the EAE mouse model for multiple sclerosis. TFM-C inhibited
secretion of IL-1beta, IL-12 and IL-17, enhanced that of TNF-alpha and RANTES,
reduced neuronal axonal damage and protected from oxidative stress in the
organotypic model. TFM-C blocked TNF-alpha release in microglial cells through a
process involving intracellular retention, but induced TNF-alpha secretion in
primary astrocyte cultures. Finally, we demonstrate that TFM-C and celecoxib
ameliorated EAE with equal potency. This coincided with reduced secretion of IL
17 and IFN-gamma by MOG-reactive T-cells and of IL-23 and inflammatory cytokines
by bone marrow-derived dendritic cells. Our study reveals that non-coxib
analogues of celecoxib may have translational value in the treatment of neuro
inflammatory conditions.
PMID- 24349444
TI - The clinical value of Huangqi injection in the treatment of leucopenia: a meta
analysis of clinical controlled trials.
AB - BACKGROUND: Huangqi injection is derived from Astragalus membranaceus root. In
China, recent reports of Huangqi injection for the treatment of leucopenia have
emerged. However, a systematic review of these reports has not been performed.
Thus, we conducted a meta-analysis of clinical controlled trials to assess the
clinical value of Huangqi injection in the treatment of leucopenia. METHODS: We
searched the Chinese Biomedical Literature Database (CBM), Wanfang Database,
China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Full
text Database (VIP), as well as PubMed and EMBASE to collect the data about
trials of Huangqi injection for treating leucopenia. A meta-analysis was
performed using RevMan 5.2 software. RESULTS: A total of 13 studies involving 841
patients were included in this study. The overall study quality was lower
according to the Jadad scale. The meta-analysis showed that experimentally
treated patients experienced greater therapeutic efficacy and lower white blood
cell counts than control groups treated with Western medicine (P < 0.05). No
publication bias was evident, according to Egger's test. CONCLUSIONS: The
validity of this meta-analysis was limited by the overall poor quality of the
included studies. Huangqi injection may have potential clinical value in the
treatment of leucopenia, but confirmation with rigorously well-designed multi
center trials is needed.
PMID- 24349443
TI - Association of TERC and OBFC1 haplotypes with mean leukocyte telomere length and
risk for coronary heart disease.
AB - OBJECTIVE: To replicate the associations of leukocyte telomere length (LTL) with
variants at four loci and to investigate their associations with coronary heart
disease (CHD) and type II diabetes (T2D), in order to examine possible causal
effects of telomere maintenance machinery on disease aetiology. METHODS: Four
SNPs at three loci BICD1 (rs2630578 GgammaC), 18q12.2 (rs2162440 GgammaT), and
OBFC1 (rs10786775 CgammaG, rs11591710 AgammaC) were genotyped in four studies
comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs
(rs12696304 CgammaG, rs10936601G>T and rs16847897 GgammaC) at the TERC locus were
genotyped in these four studies, in addition to an offspring study of 765 healthy
students. For all samples, LTL had been measured using a real-time PCR-based
method. RESULTS: Only one SNP was associated with a significant effect on LTL,
with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL
(beta=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For
OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C,
haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77;
95% CI: 0.61-0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and
rs16847897C, haplotype frequency 0.210) was associated with lower risk for both
CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61-0.91;
P= 0.004), with no effect on LTL. Only the last association remained after
adjusting for multiple testing. CONCLUSION: Of reported associations, only that
between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a
limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated
with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both
higher risk of CHD and T2D. Further work is required to confirm these results and
explore the mechanisms of these effects.
PMID- 24349445
TI - Secreted hCLCA1 is a signaling molecule that activates airway macrophages.
AB - The CLCA gene family produces both secreted and membrane-associated proteins that
modulate ion-channel function, drive mucus production and have a poorly
understood pleiotropic effect on airway inflammation. The primary up-regulated
human CLCA ortholog in airway inflammation is hCLCA1. Here we show that this
protein can activate airway macrophages, inducing them to express cytokines and
to undertake a pivotal role in airway inflammation. In a U-937 airway macrophage
monocyte cell line, conditioned media from HEK 293 cells heterologously
expressing hCLCA1 (with or without fetal bovine serum) increased the levels of
pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha and IL-8). This effect was
independent of the metalloprotease domain of hCLCA1. Primary porcine alveolar
macrophages were similarly activated, demonstrating the effect was not cell line
dependent. Similarly, immuno-purified hCLCA1 at physiologically relevant
concentration of ~100 pg/mL was able to activate macrophages and induce pro
inflammatory response. This cytokine response increased with higher concentration
of immuno-purified hCLCA1. These findings demonstrate the ability of hCLCA1 to
function as a signaling molecule and activate macrophages, central regulators of
airway inflammation.
PMID- 24349446
TI - Molecular characterization and clinical implications of spindle cells in
nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression
proposed.
AB - Up to now, the precise molecular and morphological changes underlying the
invasive and metastatic properties of nasopharyngeal carcinoma (NPC) remain
largely unresolved. We speculate that neoplastic spindle cells, which are
prominently found in the invasive tumor front and the surrounding stroma, might
be responsible for the aggressive patterns. Expression profiling of various
biomarkers relevant to cancer stem cells (CSCs) and epithelial-mesenchymal
transition (EMT) was performed by tissue microarray-based immunohistochemistry in
NPC samples. The expression of EBER and LMP1 was detected by in situ
hybridization and immunohistochemistry, respectively. We found that
overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2) and up-regulation
of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug), together
with E- to N-cadherin switching, occurred preferentially in tumors containing a
large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like
properties were highly present in spindle cells compared with non-spindle cells
of tumors, and correlated strongly with EMT features. In addition, EBV-related
factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and
EMT characteristics in neoplastic spindle cells. Importantly, high proportion of
spindle cells (>=20%) correlated significantly with various aggressive aspects
including lymph node metastasis (P = 0.031) and local recurrence (P = 0.014).
Patients with high proportion of spindle cells had poor survival (P = 0.004),
though it was not an independent value. In conclusion, we demonstrate that
spindle cells could be valuable morphological indicators of tumor progression and
unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC
firstly constructed may shed significant light on the metastatic cascade and
clinical relevance of patients.
PMID- 24349447
TI - Age-related decrements in heat dissipation during physical activity occur as
early as the age of 40.
AB - Older adults typically experience greater levels of thermal strain during
physical efforts in the heat compared to young individuals. While this may be
related to an age-dependent reduction in whole-body sweating, no study has
clearly delineated at what age this occurs. In the present study, we report
direct measurements of human heat dissipation during physical activity in the
heat in males ranging in age from 20-70 years. Eighty-five males performed four
15-min bouts of cycling separated by 15-min rest periods, in a calorimeter
regulated to 35 degrees C and 20% relative humidity. Direct calorimetry was used
to measure total heat loss (whole-body evaporative heat loss and dry heat
exchange). We also used indirect calorimetry as a continuous measure of metabolic
heat production. Body heat storage was calculated as the temporal summation of
heat production and total heat loss over the experimental session. Whole-body
sweat rate (WBSR) was calculated from measurements of evaporative heat loss.
Males were divided into five age categories for the analysis of WBSR and body
heat storage: 20-31 years (n = 18), 40-44 years (n = 15), 45-49 years (n = 15),
50-55 years (n = 21) and 56-70 years (n = 16). Relative to young males, WBSR was
reduced in males aged 56-70 during each exercise (all P<0.05), in males aged 50
55 during the second (P = 0.031) and third exercises (P = 0.028) and in males
aged 45-49 during the final exercise bout (P = 0.046). Although not significantly
different, 40-44 years old males also had a lower rate of heat loss compared to
younger males. Over the sum of two hours, the change in body heat content was
greater in males 40-70 years compared to young males (all P<0.05). Our findings
suggest that middle-aged and older adults have impairments in heat dissipation
when doing physical activity in the heat, thus possibly increasing their risk of
heat-related illness under such conditions.
PMID- 24349448
TI - A cross-sectional survey of bacterial species in plaque from client owned dogs
with healthy gingiva, gingivitis or mild periodontitis.
AB - Periodontal disease is the most widespread oral disease in dogs which if left
untreated results in significant pain to the pet and loss of dentition. The
objective of this study was to identify bacterial species in canine plaque that
are significantly associated with health, gingivitis and mild periodontitis (<25%
attachment loss). In this survey subgingival plaque samples were collected from
223 dogs with healthy gingiva, gingivitis and mild periodontitis with 72 to 77
samples per health status. DNA was extracted from the plaque samples and
subjected to PCR amplification of the V1-V3 region of the 16S rDNA.
Pyrosequencing of the PCR amplicons identified a total of 274 operational
taxonomic units after bioinformatic and statistical analysis. Porphyromonas was
the most abundant genus in all disease stages, particularly in health along with
Moraxella and Bergeyella. Peptostreptococcus, Actinomyces, and
Peptostreptococcaceae were the most abundant genera in mild periodontitis.
Logistic regression analysis identified species from each of these genera that
were significantly associated with health, gingivitis or mild periodontitis.
Principal component analysis showed distinct community profiles in health and
disease. The species identified show some similarities with health and
periodontal disease in humans but also major differences. In contrast to human,
healthy canine plaque was found to be dominated by Gram negative bacterial
species whereas Gram positive anaerobic species predominate in disease. The scale
of this study surpasses previously published research and enhances our
understanding of the bacterial species present in canine subgingival plaque and
their associations with health and early periodontal disease.
PMID- 24349449
TI - Structural propensities of human ubiquitination sites: accessibility, centrality
and local conformation.
AB - The existence and function of most proteins in the human proteome are regulated
by the ubiquitination process. To date, tens of thousands human ubiquitination
sites have been identified from high-throughput proteomic studies. However, the
mechanism of ubiquitination site selection remains elusive because of the
complicated sequence pattern flanking the ubiquitination sites. In this study, we
perform a systematic analysis of 1,330 ubiquitination sites in 505 protein
structures and quantify the significantly high accessibility and unexpectedly
high centrality of human ubiquitination sites. Further analysis suggests that the
higher centrality of ubiquitination sites is associated with the multi
functionality of ubiquitination sites, among which protein-protein interaction
sites are common targets of ubiquitination. Moreover, we demonstrate that
ubiquitination sites are flanked by residues with non-random local conformation.
Finally, we provide quantitative and unambiguous evidence that most of the
structural propensities contain specific information about ubiquitination site
selection that is not represented by the sequence pattern. Therefore, the
hypothesis about the structural level of the ubiquitination site selection
mechanism has been substantially approved.
PMID- 24349450
TI - Biotransformation of bisphenol AF to its major glucuronide metabolite reduces
estrogenic activity.
AB - Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic
activity through binding to estrogen receptor (ER). However, the metabolism of
BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In
the present study, we identified four metabolites including BPAF diglucuronide,
BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the
urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear
magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was
metabolized rapidly to BPAF-G, as detected in the plasma of SD rats.
Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes
(HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found
that BPAF glucuronidation could be mediated through several human recombinant UDP
glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4,
UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of
glucuronidation. To explain the biological function of BPAF biotransformation,
the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast
cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene
expression and cell proliferation at the dose of 100 nM and 1 MUM in breast
cancer cells. However, BPAF-G did not show any induction of estrogenic activity
at the same dosages, implying that formation of BPAF-G is a potential host
defense mechanism against BPAF. Based on our study, biotransformation of BPAF to
BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore
considered as reducing the potential threat to human beings.
PMID- 24349451
TI - A fully automated high-throughput training system for rodents.
AB - Addressing the neural mechanisms underlying complex learned behaviors requires
training animals in well-controlled tasks, an often time-consuming and labor
intensive process that can severely limit the feasibility of such studies. To
overcome this constraint, we developed a fully computer-controlled general
purpose system for high-throughput training of rodents. By standardizing and
automating the implementation of predefined training protocols within the
animal's home-cage our system dramatically reduces the efforts involved in animal
training while also removing human errors and biases from the process. We
deployed this system to train rats in a variety of sensorimotor tasks, achieving
learning rates comparable to existing, but more laborious, methods. By
incrementally and systematically increasing the difficulty of the task over weeks
of training, rats were able to master motor tasks that, in complexity and
structure, resemble ones used in primate studies of motor sequence learning. By
enabling fully automated training of rodents in a home-cage setting this low-cost
and modular system increases the utility of rodents for studying the neural
underpinnings of a variety of complex behaviors.
PMID- 24349452
TI - Alveolar macrophage innate response to Mycobacterium immunogenum, the etiological
agent of hypersensitivity pneumonitis: role of JNK and p38 MAPK pathways.
AB - Mycobacterium immunogenum is an emerging pathogen of the immune-mediated lung
disease hypersensitivity pneumonitis (HP) reported in machinists occupationally
exposed to contaminated metal working fluid (MWF). However, the mechanism of its
interaction with the host lung is unclear. Considering that alveolar macrophages
play a central role in host defense in the exposed lung, understanding their
interaction with the pathogen could provide initial insights into the underlying
immunopathogenesis events and mechanisms. In the current study, M. immunogenum
700506, a predominant genotype isolated from HP-linked fluids, was shown to
multiply intracellularly, induce proinflammatory mediators (TNF-alpha, IL-1alpha,
IL-1beta, IL-6, GM-CSF, NO) and cause cytotoxicity/cell death in the cultured
murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner.
The responses were detected as early as 3h post-infection. Comparison of this and
four additional genotypes of M. immunogenum (MJY-3, MJY-4, MJY-12, MJY-14) using
an effective dose-time combination (100 MOI for 24h) showed these macrophage
responses in the following order (albeit with some variations for individual
response indicators). Inflammatory: MJY-3 >= 700506 > MJY-4 >= MJY-14 >= MJY-12;
Cytotoxic: 700506 >= MJY-3 > MJY-4 >= MJY-12 >= MJY-14. In general, 700506 and
MJY-3 showed a more aggressive response than other genotypes. Chemical blocking
of either p38 or JNK inhibited the induction of proinflammatory mediators
(cytokines, NO) by 700506. However, the cellular responses showed a somewhat
opposite effect. This is the first report on M. immunogenum interactions with
alveolar macrophages and on the identification of JNK- and p38- mediated
signaling and its role in mediating the proinflammatory responses during these
interactions.
PMID- 24349453
TI - Hippocampal hypertrophy and sleep apnea: a role for the ischemic preconditioning?
AB - The full impact of multisystem disease such as obstructive sleep apnoea (OSA) on
regions of the central nervous system is debated, as the subsequent
neurocognitive sequelae are unclear. Several preclinical studies suggest that its
purported major culprits, intermittent hypoxia and sleep fragmentation, can
differentially affect adult hippocampal neurogenesis. Although the prospective
biphasic nature of chronic intermittent hypoxia in animal models of OSA has been
acknowledged, so far the evidence for increased 'compensatory' neurogenesis in
humans is uncertain. In a cross-sectional study of 32 patients with mixed
severity OSA and 32 non-apnoeic matched controls inferential analysis showed
bilateral enlargement of hippocampi in the OSA group. Conversely, a trend for
smaller thalami in the OSA group was noted. Furthermore, aberrant connectivity
between the hippocampus and the cerebellum in the OSA group was also suggested by
the correlation analysis. The role for the ischemia/hypoxia preconditioning in
the neuropathology of OSA is herein indicated, with possible further reaching
clinical implications.
PMID- 24349454
TI - Fitness consequences of northward dispersal as possible adaptation to climate
change, using experimental translocation of a migratory passerine.
AB - Climate change leads to rapid, differential changes in phenology across trophic
levels, often resulting in temporal mismatches between predators and their prey.
If a species cannot easily adjust its timing, it can adapt by choosing a new
breeding location with a later phenology of its prey. In this study, we
experimentally investigated whether long-distance dispersal to northern breeding
grounds with a later phenology could be a feasible process to restore the match
between timing of breeding and peak food abundance and thus improve reproductive
success. Here, we report the successful translocation of pied flycatchers
(Ficedula hypoleuca) to natural breeding sites 560 km to the Northeast. We
expected translocated birds to have a fitness advantage with respect to
environmental phenology, but to potentially pay costs through the lack of other
locally adapted traits. Translocated individuals started egg laying 11 days
earlier than northern control birds, which were translocated only within the
northern site. The number of fledglings produced was somewhat lower in
translocated birds, compared to northern controls, and fledglings were in lower
body condition. Translocated individuals were performing not significantly
different to control birds that remained at the original southern site. The lack
of advantage of the translocated individuals most likely resulted from the
exceptionally cold spring in which the experiment was carried out. Our results,
however, suggest that pied flycatchers can successfully introduce their early
breeding phenotype after dispersing to more northern areas, and thus that
adaptation through dispersal is a viable option for populations that get locally
maladapted through climate change.
PMID- 24349455
TI - Relative importance of coral cover, habitat complexity and diversity in
determining the structure of reef fish communities.
AB - The structure of coral reef habitat has a pronounced influence on the diversity,
composition and abundance of reef-associated fishes. However, the particular
features of the habitat that are most critical are not always known. Coral
habitats can vary in many characteristics, notably live coral cover, topographic
complexity and coral diversity, but the relative effects of these habitat
characteristics are often not distinguished. Here, we investigate the strength of
the relationships between these habitat features and local fish diversity,
abundance and community structure in the lagoon of Lizard Island, Great Barrier
Reef. In a spatial comparison using sixty-six 2m(2) quadrats, fish species
richness, total abundance and community structure were examined in relation to a
wide range of habitat variables, including topographic complexity, habitat
diversity, coral diversity, coral species richness, hard coral cover, branching
coral cover and the cover of corymbose corals. Fish species richness and total
abundance were strongly associated with coral species richness and cover, but
only weakly associated with topographic complexity. Regression tree analysis
showed that coral species richness accounted for most of the variation in fish
species richness (63.6%), while hard coral cover explained more variation in
total fish abundance (17.4%), than any other variable. In contrast, topographic
complexity accounted for little spatial variation in reef fish assemblages. In
degrading coral reef environments, the potential effects of loss of coral cover
and topographic complexity are often emphasized, but these findings suggest that
reduced coral biodiversity may ultimately have an equal, or greater, impact on
reef-associated fish communities.
PMID- 24349456
TI - From PII signaling to metabolite sensing: a novel 2-oxoglutarate sensor that
details PII-NAGK complex formation.
AB - The widespread PII signal transduction proteins are known for integrating signals
of nitrogen and energy supply and regulating cellular behavior by interacting
with a multitude of target proteins. The PII protein of the cyanobacterium
Synechococcus elongatus forms complexes with the controlling enzyme of arginine
synthesis, N-acetyl-L-glutamate kinase (NAGK) in a 2-oxoglutarate- and ATP/ADP
dependent manner. Fusing NAGK and PII proteins to either CFP or YFP yielded a
FRET sensor that specifically responded to 2-oxoglutarate. The impact of the
fluorescent tags on PII and NAGK was evaluated by enzyme assays, surface plasmon
resonance spectroscopy and isothermal calorimetric experiments. The developed
FRET sensor provides real-time data on PII - NAGK interaction and its modulation
by the effector molecules ATP, ADP and 2-oxoglutarate in vitro. Additionally to
its utility to monitor 2-oxoglutarate levels, the FRET assay provided novel
insights into PII - NAGK complex formation: (i) It revealed the formation of an
encounter-complex between PII and NAGK, which holds the proteins in proximity
even in the presence of inhibitors of complex formation; (ii) It revealed that
the PII T-loop residue Ser49 is neither essential for complex formation with NAGK
nor for activation of the enzyme but necessary to form a stable complex and
efficiently relieve NAGK from arginine inhibition; (iii) It showed that arginine
stabilizes the NAGK hexamer and stimulates PII - NAGK interaction.
PMID- 24349457
TI - Lung protective ventilation induces immunotolerance and nitric oxide metabolites
in porcine experimental postoperative sepsis.
AB - Low tidal volume ventilation is beneficial in patients with severe pulmonary
dysfunction and would, in theory, reduce postoperative complications if
implemented during routine surgery. The study aimed to investigate whether low
tidal volume ventilation and high positive end-expiratory pressure (PEEP) in a
large animal model of postoperative sepsis would attenuate the systemic
inflammatory response and organ dysfunction. Thirty healthy pigs were randomized
to three groups: Group Prot-7h, i.e. protective ventilation for 7 h, was
ventilated with a tidal volume of 6 mL x kg(-1) for 7 h; group Prot-5h, i.e.
protective ventilation for 5 h, was ventilated with a tidal volume of 10 mL x kg(
1) for 2 h, after which the group was ventilated with a tidal volume of 6 mL x
kg(-1); and a control group that was ventilated with a tidal volume of 10 mL x
kg(-1) for 7 h. In groups Prot-7h and Prot-5h PEEP was 5 cmH2O for 2 h and 10
cmH2O for 5 h. In the control group PEEP was 5 cmH2O for the entire experiment.
After surgery for 2 h, postoperative sepsis was simulated with an endotoxin
infusion for 5 h. Low tidal volume ventilation combined with higher PEEP led to
lower levels of interleukin 6 and 10 in plasma, higher PaO2/FiO2, better
preserved functional residual capacity and lower plasma troponin I as compared
with animals ventilated with a medium high tidal volume and lower PEEP. The
beneficial effects of protective ventilation were seen despite greater reductions
in cardiac index and oxygen delivery index. In the immediate postoperative phase
low VT ventilation with higher PEEP was associated with reduced ex vivo plasma
capacity to produce TNF-alpha upon endotoxin stimulation and higher nitrite
levels in urine. These findings might represent mechanistic explanations for the
attenuation of systemic inflammation and inflammatory-induced organ dysfunction.
PMID- 24349458
TI - Inflammasome-mediated inhibition of Listeria monocytogenes-stimulated immunity is
independent of myelomonocytic function.
AB - Activation of the Nlrc4 inflammasome results in the secretion of IL-1beta and IL
18 through caspase-1 and induction of pyroptosis. L. monocytogenes engineered to
activate Nlrc4 by expression of Legionella pneumophilia flagellin (L.
monocytogenes L.p.FlaA) are less immunogenic for CD8(+) T cell responses than wt
L. monocytogenes. It is also known that IL-1beta orchestrates recruitment of
myelomonocytic cells (MMC), which have been shown to interfere with T cell
dendritic cells (DC) interactions in splenic white pulp (WP), limiting T cell
priming and protective immunity. We have further analyzed the role of MMCs in the
immunogenicity of L. monocytogenes L.p.FlaA. We confirmed that MMCs infiltrate
the WP between 24-48 hours in response to wt L. monocytogenes infection and that
depletion of MMCs enhances CD8(+) T cell priming and protective memory. L.
monocytogenes L.p.FlaA elicited accelerated recruitment of MMCs into the WP.
While MMCs contribute to control of L. monocytogenes L.p.FlaA, MMC depletion did
not increase immunogenicity of L.p.FlaA expressing strains. There was a
significant decrease in L. monocytogenes L.p.FlaA in CD8alpha(+) DCs independent
of MMCs. These findings suggest that limiting inflammasome activation is
important for bacterial accumulation in CD8alpha(+) DCs, which are known to be
critical for T cell response to L. monocytogenes.
PMID- 24349459
TI - Pegylated interferon-alpha2a inhibits proliferation of human liver cancer cells
in vitro and in vivo.
AB - PURPOSE: We investigated the effects of pegylated interferon-alpha2a (PEG-IFN
alpha2a) on the growth of human liver cancer cells. METHODS: The effect of PEG
IFN-alpha2a on the proliferation of 13 liver cancer cell lines was investigated
in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN
alpha2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and
growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B
and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-alpha2a
were subcutaneously administered to the mice once a week for 2 weeks, and tumor
volume, weight, and histology were examined. RESULTS: PEG-IFN-alpha2a inhibited
the growth of 8 and 11 cell lines in a time- and dose-dependent manner,
respectively, although the 50% growth inhibitory concentrations of 7 measurable
cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431
ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG
IFN-alpha2a induced a dose-dependent decrease in tumor volume and weight, and a
significant increase of apoptotic cells in the tumor. Subcutaneous administration
of clinical dose for chronic hepatitis C (3 MUg/kg, 0.06 MUg/mouse) was effective
and induced about 30-50% reduction in the tumor volume and weight as compared
with the control. CONCLUSIONS: Although in vitro anti-proliferative effects of
PEG-IFN-alpha2a were relatively weak, PEG-IFN-alpha2a induced strong anti-tumor
effects on HCC cells in vivo. The data suggest potential clinical application of
PEG-IFN-alpha2a for the prevention and treatment of HCC.
PMID- 24349460
TI - Defense responses in two ecotypes of Lotus japonicus against non-pathogenic
Pseudomonas syringae.
AB - Lotus japonicus is a model legume broadly used to study many important processes
as nitrogen fixing nodule formation and adaptation to salt stress. However, no
studies on the defense responses occurring in this species against invading
microorganisms have been carried out at the present. Understanding how this model
plant protects itself against pathogens will certainly help to develop more
tolerant cultivars in economically important Lotus species as well as in other
legumes. In order to uncover the most important defense mechanisms activated upon
bacterial attack, we explored in this work the main responses occurring in the
phenotypically contrasting ecotypes MG-20 and Gifu B-129 of L. japonicus after
inoculation with Pseudomonas syringae DC3000 pv. tomato. Our analysis
demonstrated that this bacterial strain is unable to cause disease in these
accessions, even though the defense mechanisms triggered in these ecotypes might
differ. Thus, disease tolerance in MG-20 was characterized by bacterial
multiplication, chlorosis and desiccation at the infiltrated tissues. In turn,
Gifu B-129 plants did not show any symptom at all and were completely successful
in restricting bacterial growth. We performed a microarray based analysis of
these responses and determined the regulation of several genes that could play
important roles in plant defense. Interestingly, we were also able to identify a
set of defense genes with a relative high expression in Gifu B-129 plants under
non-stress conditions, what could explain its higher tolerance. The participation
of these genes in plant defense is discussed. Our results position the L.
japonicus-P. syringae interaction as a interesting model to study defense
mechanisms in legume species.
PMID- 24349462
TI - Integrating the meaning of person names into discourse context: an event-related
potential study.
AB - The meaning of person names is determined by their associated information. This
study used event related potentials to investigate the time course of integrating
the newly constructed meaning of person names into discourse context. The meaning
of person names was built by two-sentence descriptions of the names. Then we
manipulated the congruence of person names relative to discourse context in a way
that the meaning of person names either matched or did not match the previous
context. ERPs elicited by the names were compared between the congruent and the
incongruent conditions. We found that the incongruent names elicited a larger
N400 as well as a larger P600 compared to the congruent names. The results
suggest that the meaning of unknown names can be effectively constructed from
short linguistic descriptions and that the established meaning can be rapidly
retrieved and integrated into contexts.
PMID- 24349461
TI - Influence of APOE genotype on whole-brain functional networks in cognitively
normal elderly.
AB - This study aimed to investigate the influence of apolipoprotein E (APOE) epsilon4
allele on whole-brain functional networks in cognitively normal (CN) elderly by
applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN
elderly [28 APOE epsilon4 carriers (epsilon4+) and 58 non-carriers (epsilon4-)]
underwent clinical evaluation and resting [(18)F] fluorodeoxyglucose positron
emission tomography scan. Whole-brain functional networks were constructed from
correlations of the 90 regions of interest using the automated anatomical
labeling template, and analyzed using graph theoretical approaches. The overall
small-world property seen in epsilon4- was preserved in epsilon4+. However, both
local clustering and path length were lower in epsilon4+ compared to epsilon4-.
In terms of the hubs of functional networks, epsilon4+ showed decreased
centrality of the right hippocampus but increased centrality of several brain
regions associated with the default mode network compared to epsilon4-. Our
results indicate that genetic vulnerability to Alzheimer's disease may alter
whole-brain functional networks even before clinical symptoms appear.
PMID- 24349463
TI - Elucidation of molecular mechanisms of physiological variations between bovine
subcutaneous and visceral fat depots under different nutritional regimes.
AB - Adipose tissue plays a critical role in energy homeostasis and metabolism. There
is sparse understanding of the molecular regulation at the protein level of
bovine adipose tissues, especially within different fat depots under different
nutritional regimes. The objective of this study was to analyze the differences
in protein expression between bovine subcutaneous and visceral fat depots in
steers fed different diets and to identify the potential regulatory molecular
mechanisms of protein expression. Subcutaneous and visceral fat tissues were
collected from 16 British-continental steers (15.5 month old) fed a high-fat diet
(7.1% fat, n=8) or a control diet (2.7% fat, n=8). Protein expression was
profiled using label free quantification LC-MS/MS and expression of selected
transcripts was evaluated using qRT-PCR. A total of 682 proteins were
characterized and quantified with fat depot having more impact on protein
expression, altering the level of 51.0% of the detected proteins, whereas diet
affected only 5.3%. Functional analysis revealed that energy production and lipid
metabolism were among the main functions associated with differentially expressed
proteins between fat depots, with visceral fat being more metabolically active
than subcutaneous fat as proteins associated with lipid and energy metabolism
were upregulated. The expression of several proteins was significantly correlated
to subcutaneous fat thickness and adipocyte size, indicating their potential as
adiposity markers. A poor correlation (r=0.245) was observed between mRNA and
protein levels for 9 genes, indicating that many proteins may be subjected to
post-transcriptional regulation. A total of 8 miRNAs were predicted to regulate
more than 20% of lipid metabolism proteins differentially expressed between fat
depots, suggesting that miRNAs play a role in adipose tissue regulation. Our
results show that proteomic changes support the distinct metabolic and
physiological characteristics observed between subcutaneous and visceral adipose
tissue depots in cattle.
PMID- 24349464
TI - ADP protects cardiac mitochondria under severe oxidative stress.
AB - ADP is not only a key substrate for ATP generation, but also a potent inhibitor
of mitochondrial permeability transition pore (mPTP). In this study, we assessed
how oxidative stress affects the potency of ADP as an mPTP inhibitor and whether
its reduction of reactive oxygen species (ROS) production might be involved. We
determined quantitatively the effects of ADP on mitochondrial Ca(2+) retention
capacity (CRC) until the induction of mPTP in normal and stressed isolated
cardiac mitochondria. We used two models of chronic oxidative stress (old and
diabetic mice) and two models of acute oxidative stress (ischemia reperfusion
(IR) and tert-butyl hydroperoxide (t-BH)). In control mitochondria, the CRC was
344 +/- 32 nmol/mg protein. 500 MUmol/L ADP increased CRC to 774 +/- 65 nmol/mg
protein. This effect of ADP seemed to relate to its concentration as 50 MUmol/L
had a significantly smaller effect. Also, oligomycin, which inhibits the
conversion of ADP to ATP by F0F1ATPase, significantly increased the effect of 50
MUmol/L ADP. Chronic oxidative stress did not affect CRC or the effect of 500
MUmol/L ADP. After IR or t-BH exposure, CRC was drastically reduced to 1 +/- 0.2
and 32 +/- 4 nmol/mg protein, respectively. Surprisingly, ADP increased the CRC
to 447 +/- 105 and 514 +/- 103 nmol/mg protein in IR and t-BH, respectively.
Thus, it increased CRC by the same amount as in control. In control mitochondria,
ADP decreased both substrate and Ca(2+)-induced increase of ROS. However, in t-BH
mitochondria the effect of ADP on ROS was relatively small. We conclude that ADP
potently restores CRC capacity in severely stressed mitochondria. This effect is
most likely not related to a reduction in ROS production. As the effect of ADP
relates to its concentration, increased ADP as occurs in the pathophysiological
situation may protect mitochondrial integrity and function.
PMID- 24349465
TI - Identification of putative target genes of the transcription factor RUNX2.
AB - Comparisons of the genomes of Neandertals and Denisovans with present-day human
genomes have suggested that the gene RUNX2, which encodes a transcription factor,
may have been positively selected during early human evolution. Here, we
overexpress RUNX2 in ten human cell lines and identify genes that are directly or
indirectly affected by RUNX2 expression. We find a number of genes not previously
known to be affected by RUNX2 expression, in particular BIRC3, genes encoded on
the mitochondrial genome, and several genes involved in bone and tooth formation.
These genes are likely to provide inroads into pathways affected by RUNX2 and
potentially by the evolutionary changes that affected RUNX2 in modern humans.
PMID- 24349467
TI - Worldwide topology of the scientific subject profile: a macro approach in the
country level.
AB - BACKGROUND: Models for the production of knowledge and systems of innovation and
science are key elements for characterizing a country in view of its scientific
thematic profile. With regard to scientific output and publication in journals of
international visibility, the countries of the world may be classified into three
main groups according to their thematic bias. METHODOLOGY/PRINCIPAL FINDINGS:
This paper aims to classify the countries of the world in several broad groups,
described in terms of behavioural models that attempt to sum up the
characteristics of their systems of knowledge and innovation. We perceive three
clusters in our analysis: 1) the biomedical cluster, 2) the basic science &
engineering cluster, and 3) the agricultural cluster. The countries are
conceptually associated with the clusters via Principal Component Analysis (PCA),
and a Multidimensional Scaling (MDS) map with all the countries is presented.
CONCLUSIONS/SIGNIFICANCE: As we have seen, insofar as scientific output and
publication in journals of international visibility is concerned, the countries
of the world may be classified into three main groups according to their thematic
profile. These groups can be described in terms of behavioral models that attempt
to sum up the characteristics of their systems of knowledge and innovation.
PMID- 24349466
TI - Dynamics of defense responses and cell fate change during Arabidopsis-Pseudomonas
syringae interactions.
AB - Plant-pathogen interactions involve sophisticated action and counteraction
strategies from both parties. Plants can recognize pathogen derived molecules,
such as conserved pathogen associated molecular patterns (PAMPs) and effector
proteins, and subsequently activate PAMP-triggered immunity (PTI) and effector
triggered immunity (ETI), respectively. However, pathogens can evade such
recognitions and suppress host immunity with effectors, causing effector
triggered susceptibility (ETS). The differences among PTI, ETS, and ETI have not
been completely understood. Toward a better understanding of PTI, ETS, and ETI,
we systematically examined various defense-related phenotypes of Arabidopsis
infected with different Pseudomonas syringae pv. maculicola ES4326 strains, using
the virulence strain DG3 to induce ETS, the avirulence strain DG34 that expresses
avrRpm1 (recognized by the resistance protein RPM1) to induce ETI, and HrcC(-)
that lacks the type three secretion system to activate PTI. We found that plants
infected with different strains displayed dynamic differences in the accumulation
of the defense signaling molecule salicylic acid, expression of the defense
marker gene PR1, cell death formation, and accumulation/localization of the
reactive oxygen species, H2O2. The differences between PTI, ETS, and ETI are
dependent on the doses of the strains used. These data support the quantitative
nature of PTI, ETS, and ETI and they also reveal qualitative differences between
PTI, ETS, and ETI. Interestingly, we observed the induction of large cells in the
infected leaves, most obviously with HrcC(-) at later infection stages. The
enlarged cells have increased DNA content, suggesting a possible activation of
endoreplication. Consistent with strong induction of abnormal cell growth by
HrcC(-), we found that the PTI elicitor flg22 also activates abnormal cell
growth, depending on a functional flg22-receptor FLS2. Thus, our study has
revealed a comprehensive picture of dynamic changes of defense phenotypes and
cell fate determination during Arabidopsis-P. syringae interactions, contributing
to a better understanding of plant defense mechanisms.
PMID- 24349468
TI - Physiological mechanisms for high salt tolerance in wild soybean (Glycine soja)
from Yellow River Delta, China: photosynthesis, osmotic regulation, ion flux and
antioxidant capacity.
AB - Glycine soja (BB52) is a wild soybean cultivar grown in coastal saline land in
Yellow River Delta, China. In order to reveal the physiological mechanisms
adapting to salinity, we examined photosynthesis, ion flux, antioxidant system
and water status in Glycine soja under NaCl treatments, taking a cultivated
soybean, ZH13, as control. Upon NaCl exposure, higher relative water content and
water potential were maintained in the leaf of BB52 than ZH13, which might depend
on the more accumulation of osmotic substances such as glycinebetaine and
proline. Compared with ZH13, activities of antioxidant enzymes including
superoxide dismutase, catalase, ascorbate peroxidase and contents of ascorbate,
glutathione and phenolics were enhanced to a higher level in BB52 leaf under NaCl
stress, which could mitigate the salt-induced oxidative damage in BB52.
Consistently, lipid peroxidation indicated by malondialdehyde content was lower
in BB52 leaf. Photosynthetic rate (Pn) was decreased by NaCl stress in BB52 and
ZH13, and the decrease was greater in ZH13. The decreased Pn in BB52 was mainly
due to stomatal limitation. The inhibited activation of rubisco enzyme in ZH13
due to the decrease of rubisco activase content became an important limiting
factor of Pn, when NaCl concentration increased to 200 mM. Rubisco activase in
BB52 was not affected by NaCl stress. Less negative impact in BB52 derived from
lower contents of Na(+) and Cl(-) in the tissues, and non-invasive micro-test
technique revealed that BB52 roots had higher ability to extrude Na(+) and Cl(-).
Wild soybean is a valuable genetic resource, and our study may provide a
reference for molecular biologist to improve the salt tolerance of cultivated
soybean in face of farmland salinity.
PMID- 24349469
TI - B-lymphocytes as key players in chemical-induced asthma.
AB - T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B
lymphocytes producing antigen-specific immunoglobulins E (IgE). We used a mouse
model of chemical-induced asthma and transferred B-lymphocytes from sensitized
animals into naive wild type mice, B-lymphocyte knock-out (B-KO) mice or severe
combined immunodeficiency (SCID) mice. On days 1 and 8, BALB/c mice were dermally
sensitized with 0.3% toluene diisocyanate (TDI) (20 ul/ear). On day 15, mice were
euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+)) were
separated from the whole cell suspension and 175,000 cells were injected in the
tail vein of naive wild type, B-KO or SCID mice. Three days later, the mice
received a single oropharyngeal challenge with 0.01% TDI (20 ul) or vehicle
(acetone/olive oil (AOO)) (controls). Airway reactivity to methacholine and total
and differential cell counts in the bronchoalveolar lavage (BAL) fluid were
measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice
were characterized for the expression of surface markers and production of
cytokines. We found that transfer of B-cells obtained from mice dermally
sensitized to toluene diisocyanate (TDI) into naive wild type mice, B-KO mice or
SCID mice led, within three days, to an acute asthma-like phenotype after an
airway challenge with TDI. This response was specific and independent of IgE.
These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40) and
consisted of B effector (Be)2- (IL-4) and Be1-lymphocytes (IFN-gamma). The
transferred B-lymphocytes were visualized near large airways, 24 hours after TDI
challenge. Thus, B-lymphocytes can provoke an asthmatic response without the
action of T-lymphocytes and without major involvement of IgE.
PMID- 24349470
TI - First-in-human phase I study of PRS-050 (Angiocal), an Anticalin targeting and
antagonizing VEGF-A, in patients with advanced solid tumors.
AB - BACKGROUND: To report the nonrandomized first-in-human phase I trial of PRS-050,
a novel, rationally engineered Anticalin based on human tear lipocalin that
targets and antagonizes vascular endothelial growth factor A (VEGF-A). METHODS:
Patients with advanced solid tumors received PRS-050 at 0.1 mg/kg to 10 mg/kg by
IV in successive dosing cohorts according to the 3+3 escalation scheme. The
primary end point was safety. RESULTS: Twenty-six patients were enrolled; 25 were
evaluable. Two patients experienced dose-limiting toxicity, comprising grade (G)
3 hypertension and G3 pyrexia, respectively. The maximum tolerated dose was not
reached. Most commonly reported treatment-emergent adverse events (AEs) included
chills (52%; G3, 4%), fatigue (52%; G3, 4%), hypertension (44%; G3, 16%), and
nausea (40%, all G1/2). No anti-PRS-050 antibodies following multiple
administration of the drug were detected. PRS-050 showed dose-proportional
pharmacokinetics (PK), with a terminal half-life of approximately 6 days. Free
VEGF-A was detectable at baseline in 9/25 patients, becoming rapidly undetectable
after PRS-050 infusion for up to 3 weeks. VEGF-A/PRS-050 complex was detectable
for up to 3 weeks at all dose levels, including in patients without detectable
baseline-free VEGF-A. We also detected a significant reduction in circulating
matrix metalloproteinase 2, suggesting this end point could be a pharmacodynamic
(PD) marker of the drug's activity. CONCLUSIONS: PRS-050, a novel Anticalin with
high affinity for VEGF-A, was well-tolerated when administered at the highest
dose tested, 10 mg/kg. Based on target engagement and PK/PD data, the recommended
phase II dose is 5 mg/kg every 2 weeks administered as a 120-minute infusion.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01141257
http://clinicaltrials.gov/ct2/show/NCT01141257.
PMID- 24349471
TI - Inflammation but not dietary macronutrients insufficiency associated with the
malnutrition-inflammation score in hemodialysis population.
AB - Malnutrition is associated with increased risk of mortality in hemodialysis
patients. And insufficient dietary intake is the common cause for malnutrition.
So, in order to survey the dietary intake of hemodialysis patients and study the
relationship between the dietary feature and nutritional status, a cross
sectional study was performed. 75 hemodialysis patients from South China
participated in the dietary intake survey and nutrition assessment. A three-day
diet diary record was used to estimate the major dietary macronutrients.
Nutritional status was assessed by malnutrition-inflammation score (MIS) in
addition to several related anthropometric measurements. Serum albumin,
transferrin, and high-sensitivity C-reactive protein (CRP) were measured.
Receiver operating characteristic (ROC) curve analysis was used to quantify the
assessing value of independent parameters for nutritional status. The results
showed that 48% patients were malnourished according to the MIS. The malnourished
patients had a lower body mass index (BMI), fat mass (FM), albumin and a higher
level of CRP, compared with normal nourished patients (P < 0.05). However, no
significant differences of macronutrients (calories, protein, fat, carbohydrates,
etc) were found between the two nutrition groups (P > 0.05). The multivariate
regression analysis showed that the major macronutrients had no significant
association with MIS (P > 0.05). In conclusion, malnutrition is very common in
South China hemodialysis population and these data indicated that inflammation
but not dietary macronutrients insufficiency might be the candidate cause for
malnutrition in hemodialysis population.
PMID- 24349472
TI - Cinnamon counteracts the negative effects of a high fat/high fructose diet on
behavior, brain insulin signaling and Alzheimer-associated changes.
AB - Insulin resistance leads to memory impairment. Cinnamon (CN) improves peripheral
insulin resistance but its effects in the brain are not known. Changes in
behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain
were measured in male Wistar rats fed a high fat/high fructose (HF/HFr) diet to
induce insulin resistance, with or without CN, for 12 weeks. There was a decrease
in insulin sensitivity associated with the HF/HFr diet that was reversed by CN.
The CN fed rats were more active in a Y maze test than rats fed the control and
HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus
maze test that was lessened by feeding CN. The HF/HFr diet also led to a down
regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the
hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the
hippocampus and cortex due to the HF/HFr diet that were not reversed by CN.
Increased peripheral insulin sensitivity was also associated with increased
glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet
animals fed CN. The HF/HFr diet induced increases in mRNA associated with
Alzheimers including PTEN, Tau and amyloid precursor protein (App) were also
alleviated by CN. In conclusion, these data suggest that the negative effects of
a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated
changes were alleviated by CN suggesting that neuroprotective effects of CN are
associated with improved whole body insulin sensitivity and related changes in
the brain.
PMID- 24349473
TI - Whole exome sequencing identifies novel recurrently mutated genes in patients
with splenic marginal zone lymphoma.
AB - The pathogenesis of splenic marginal zone lymphoma (SMZL) remains largely
unknown. Recent high-throughput sequencing studies have identified recurrent
mutations in key pathways, most notably NOTCH2 mutations in >25% of patients.
These studies are based on small, heterogeneous discovery cohorts, and therefore
only captured a fraction of the lesions present in the SMZL genome. To identify
further novel pathogenic mutations within related biochemical pathways, we
applied whole exome sequencing (WES) and copy number (CN) analysis to a
biologically and clinically homogeneous cohort of seven SMZL patients with 7q
abnormalities and IGHV1-2*04 gene usage. We identified 173 somatic non-silent
variants, affecting 160 distinct genes. In additional to providing independent
validation of the presence of mutation in several previously reported genes
(NOTCH2, TNFAIP3, MAP3K14, MLL2 and SPEN), our study defined eight additional
recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4,
FBXO11, PLA2G4D, TRRAP and USH2A. By integrating our WES and CN data we
identified three mutated putative candidate genes targeted by 7q deletions (CUL1,
EZH2 and FLNC), with FLNC positioned within the well-characterized 7q minimally
deleted region. Taken together, this work expands the reported directory of
recurrently mutated cancer genes in this disease, thereby expanding our
understanding of SMZL pathogenesis. Ultimately, this work will help to establish
a stratified approach to care including the possibility of targeted therapy.
PMID- 24349474
TI - LipL41, a hemin binding protein from Leptospira santarosai serovar Shermani.
AB - Leptospirosis is one of the most widespread zoonotic diseases in the world. It is
caused by the pathogen Leptospira that results in multiple-organ failure, in
particular of the kidney. Outer membrane lipoprotein is the suspected virulence
factor of Leptospira. In Leptospira spp LipL41 is one major lipoprotein and is
highly conserved. Previous study suggests that LipL41 bears hemin-binding ability
and might play a possible role in iron regulation and storage. However, the
characterization of hemin-binding ability of LipL41 is still unclear. Here the
hemin-binding ability of LipL41 was examined, yielding a K d = 0.59 +/- 0.14 MUM.
Two possible heme regulatory motifs (HRMs), C[P/S], were found in LipL41 at
(140)Cys-Ser and (220)Cys-Pro. The mutation study indicates that Cys140 and
Cys220 might be cooperatively involved in hemin binding. A supramolecular
assembly of LipL41 was determined by transmission electron microscopy. The LipL41
oligomer consists of 36 molecules and folds as a double-layered particle. At the
C-terminus of LipL41, there are two tetratricopeptide repeats (TPRs), which might
be involved in the protein-protein interaction of the supramolecular assembly.
PMID- 24349475
TI - Genetic variability and population structure of the mushroom Pleurotus eryngii
var. tuoliensis.
AB - The genetic diversity of 123 wild strains of Pleurotus eryngii var. tuoliensis,
which were collected from nine geographical locations in Yumin, Tuoli, and Qinghe
counties in the Xinjiang Autonomous Region of China, was analysed using two
molecular marker systems (inter-simple sequence repeat and start codon targeted).
At the variety level, the percentage of polymorphic loci and Nei's gene diversity
index for P. eryngii var. tuoliensis was 96.32% and 0.238, respectively. At the
population level, Nei's gene diversity index ranged from 0.149 to 0.218 with an
average of 0.186, and Shannon's information index ranged from 0.213 to 0.339 with
an average of 0.284. These results revealed the abundant genetic variability in
the wild resources of P. eryngii var. tuoliensis. Nei's gene diversity analysis
indicated that the genetic variance was mainly found within individual
geographical populations, and the analysis of molecular variance revealed low but
significant genetic differentiation among local and regional populations. The
limited gene flow (Nm = 1.794) was inferred as a major reason for the extent of
genetic differentiation of P. eryngii var. tuoliensis. The results of Mantel
tests showed that the genetic distance among geographical populations of P.
eryngii var. tuoliensis was positively correlated with the geographical distance
and the longitudinal distances (rGo = 0.789 and rLn = 0.873, respectively), which
indicates that geographical isolation is an important factor for the observed
genetic differentiation. Nine geographical populations of P. eryngii var.
tuoliensis were divided into three groups according to their geographical
origins, which revealed that the genetic diversity was closely related to the
geographical distribution of this wild fungus.
PMID- 24349476
TI - Histone H4R3 methylation catalyzed by SKB1/PRMT5 is required for maintaining
shoot apical meristem.
AB - The shoot apical meristem (SAM) is the source of all of the above-ground tissues
and organs in post-embryonic development in higher plants. Studies have proven
that the expression of genes constituting the WUSCHEL (WUS)-CLAVATA (CLV)
feedback loop is critical for the SAM maintenance. Several histone lysine
acetylation and methylation markers have been proven to regulate the
transcription level of WUS. However, little is known about how histone arginine
methylation regulates the expression of WUS and other genes. Here, we report that
H4R3 symmetric dimethylation (H4R3sme2) mediated by SKB1/PRMT5 represses the
expression of CORYNE (CRN) to maintain normal SAM geometrics. SKB1 lesion results
in small SAM size in Arabidopsis, as well as down-regulated expression of WUS and
CLV3. Up-regulation of WUS expression enlarges SAM size in skb1 mutant plants. We
find that SKB1 and H4R3sme2 associate with the chromatin of the CRN locus to down
regulate its transcription. Mutation of CRN rescues the expression of WUS and the
small SAM size of skb1. Thus, SKB1 and SKB1-mediated H4R3sme2 are required for
the maintenance of SAM in Arabidopsis seedlings.
PMID- 24349477
TI - The effect of an adding histidine on biological activity and stability of Pc-pis
from Pseudosciaena crocea.
AB - Pc-pis is a novel piscidin-like antimicrobial polypeptide that was identified in
Pseudosciaena crocea. Although active against most bacteria tested, Pc-pis was
inactive against Aeromonas hydrophila and Pseudomonas aeruginosa. The Pc-pis
analogue Pc-pis-His was designed by adding a histidine residue at the carboxyl
terminal. Pc-pis-His demonstrated a more broad-spectrum and stronger
antimicrobial activity against a representative set of microorganisms and more
potent antiparasitic activity against Cryptocaryon irritans trophonts than Pc
pis. The stability assay revealed that Pc-pis-His was active against
Staphylococcus aureus not only in acidic (pH 5.5-7.3) and relatively low
concentration monovalent cation (0-160 mM NaCl) environments but also in alkaline
(pH 7.5-9.5), divalent cation (1.25-160 mM MgCl2 and 1.25-40 mM CaCl2) and high
concentration monovalent cation (320-2560 mM NaCl) environments, which indicates
that the added histidine residue conferred better salt-, acid- and alkali
tolerance to Pc-pis-His. Pc-pis-His also possessed the desired heat-tolerance,
which was reflected by the antimicrobial activity of the peptide after being
boiled for 10-60 minutes. Hemolytic activity analysis revealed that Pc-pis-His at
concentrations up to 6 uM exhibited no hemolysis against human erythrocytes, with
6 uM being a concentration that is highly active against most of the
microorganisms tested, although the hemolytic activity of Pc-pis-His was enhanced
compared to Pc-pis. These results provide a unique, reasonable basis for
designing novel piscidins with potent, broad-spectrum and stable antimicrobial
activity and new insight into the future development of piscidins as potential
therapeutic agents against microbial and external protozoan parasite infections.
PMID- 24349478
TI - A regression-based method for estimating risks and relative risks in case-base
studies.
AB - Both the absolute risk and the relative risk (RR) have a crucial role to play in
epidemiology. RR is often approximated by odds ratio (OR) under the rare-disease
assumption in conventional case-control study; however, such a study design does
not provide an estimate for absolute risk. The case-base study is an alternative
approach which readily produces RR estimation without resorting to the rare
disease assumption. However, previous researchers only considered one single
dichotomous exposure and did not elaborate how absolute risks can be estimated in
a case-base study. In this paper, the authors propose a logistic model for the
case-base study. The model is flexible enough to admit multiple exposures in any
measurement scale-binary, categorical or continuous. It can be easily fitted
using common statistical packages. With one additional step of simple
calculations of the model parameters, one readily obtains relative and absolute
risk estimates as well as their confidence intervals. Monte-Carlo simulations
show that the proposed method can produce unbiased estimates and adequate
coverage confidence intervals, for ORs, RRs and absolute risks. The case-base
study with all its desirable properties and its methods of analysis fully
developed in this paper may become a mainstay in epidemiology.
PMID- 24349479
TI - Pain and disgust: the facial signaling of two aversive bodily experiences.
AB - The experience of pain and disgust share many similarities, given that both are
aversive experiences resulting from bodily threat and leading to defensive
reactions. The aim of the present study was to investigate whether facial
expressions are distinct enough to encode the specific quality of pain and
disgust or whether they just encode the similar negative valence and arousal
level of both states. In sixty participants pain and disgust were induced by heat
stimuli and pictures, respectively. Facial responses (Facial Action Coding
System) as well as subjective responses were assessed. Our main findings were
that nearly the same single facial actions were elicited during pain and disgust
experiences. However, these single facial actions were displayed with different
strength and were differently combined depending on whether pain or disgust was
experienced. Whereas pain was mostly encoded by contraction of the muscles
surrounding the eyes (by itself or in combination with contraction of the
eyebrows); disgust was mainly accompanied by contraction of the eyebrows and--in
contrast to pain--by raising of the upper lip as well as the combination of upper
lip raise and eyebrow contraction. Our data clearly suggests that facial
expressions seem to be distinct enough to encode not only the general valence and
arousal associated with these two bodily aversive experiences, namely pain and
disgust, but also the specific origin of the threat to the body. This implies
that the differential decoding of these two states by an observer is possible
without additional verbal or contextual information, which is of special interest
for clinical practice, given that raising awareness in observers about these
distinct differences could help to improve the detection of pain in patients who
are not able to provide a self-report of pain (e.g., patients with dementia).
PMID- 24349480
TI - Novel targets of sulforaphane in primary cardiomyocytes identified by proteomic
analysis.
AB - Cardiovascular diseases represent the main cause of mortality in the
industrialized world and the identification of effective preventive strategies is
of fundamental importance. Sulforaphane, an isothiocyanate from cruciferous
vegetables, has been shown to up-regulate phase II enzymes in cardiomyocytes and
counteract oxidative stress-induced apoptosis. Aim of the present study was the
identification and characterization of novel sulforaphane targets in
cardiomyocytes applying a proteomic approach. Two-dimensional gel electrophoresis
and mass spectrometry were used to generate protein profiles of primary neonatal
rat cardiomyocytes treated and untreated with 5 uM sulforaphane for 1-48 h.
According to image analysis, 64 protein spots were found as differentially
expressed and their functional correlations were investigated using the MetaCore
program. We mainly focused on 3 proteins: macrophage migration inhibitory factor
(MIF), CLP36 or Elfin, and glyoxalase 1, due to their possible involvement in
cardioprotection. Validation of the time-dependent differential expression of
these proteins was performed by western blotting. In particular, to gain insight
into the cardioprotective role of the modulation of glyoxalase 1 by sulforaphane,
further experiments were performed using methylglyoxal to mimic glycative stress.
Sulforaphane was able to counteract methylglyoxal-induced apoptosis, ROS
production, and glycative stress, likely through glyoxalase 1 up-regulation. In
this study, we reported for the first time new molecular targets of sulforaphane,
such as MIF, CLP36 and glyoxalase 1. In particular, we gave new insights into the
anti-glycative role of sulforaphane in cardiomyocytes, confirming its pleiotropic
behavior in counteracting cardiovascular diseases.
PMID- 24349481
TI - A phenotypic screen in zebrafish identifies a novel small-molecule inducer of
ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP
signaling.
AB - Zebrafish have recently emerged as an attractive model for the in vivo bioassay
guided isolation and characterization of pharmacologically active small molecules
of natural origin. We carried out a zebrafish-based phenotypic screen of over
3000 plant-derived secondary metabolite extracts with the goal of identifying
novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the
bioactive plant extracts identified in this screen - Jasminum gilgianum, an
Oleaceae species native to Papua New Guinea - induced ectopic tails during
zebrafish embryonic development. As ectopic tail formation occurs when BMP or non
canonical Wnt signaling is inhibited during the tail protrusion process, we
suspected a constituent of this extract to act as a modulator of these pathways.
A bioassay-guided isolation was carried out on the basis of this zebrafish
phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active
compound. We then performed an in-depth phenotypic analysis of pCAME-treated
zebrafish embryos, including a tissue-specific marker analysis of the secondary
tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN
193189 in inducing ectopic tails, and causing convergence-extension defects in
compound-treated embryos. These results indicate that pCAME may interfere with
non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP
signaling (via morpholino antisense knockdown and pharmacological inhibition with
the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However,
immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated
phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other
pathways, as possibly being involved in the ectopic tail formation activity of
pCAME. Further investigation of pCAME's mechanism of action will help determine
this compound's pharmacological utility.
PMID- 24349482
TI - microRNA 126 inhibits the transition of endothelial progenitor cells to
mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.
AB - AIMS: Endothelial progenitor cells (EPCs) are capable of proliferating and
differentiating into mature endothelial cells, and they have been considered as
potential candidates for coronary heart disease therapy. However, the transition
of EPCs to mesenchymal cells is not fully understood. This study aimed to explore
the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition
(EndMT) induced by transforming growth factor beta 1 (TGFbeta1). METHODS AND
RESULTS: EndMT of rat bone marrow-derived EPCs was induced by TGFbeta1 (5 ng/mL)
for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The
luciferase reporter assay showed that the PI3K regulatory subunit p85 beta
(PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a
lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression
of mesenchymal cell markers (alpha-SMA, sm22-a, and myocardin) and to maintain
the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular
process of EndMT, there was an increase in the protein expression of PIK3R2 and
the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt
expression decreased, a change that was reversed markedly by overexpression of
miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed
morphological changes of the EPCs treated with TGFbeta1, thereby giving the
evidence that PIK3R2 is the target gene of miR-126 during EndMT process.
CONCLUSIONS: These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT
and that this process involves regulation of the PI3K/Akt signalling pathway. miR
126 has the potential to be used as a biomarker for the early diagnosis of
intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool
for treating cardiovascular diseases mediated by the EndMT process.
PMID- 24349483
TI - Molecular characterization of a new Babesia bovis thrombospondin-related
anonymous protein (BbTRAP2).
AB - A gene encoding a Babesia bovis protein that shares significant degree of
similarity to other apicomplexan thrombospondin-related anonymous proteins
(TRAPs) was found in the genomic database and designated as BbTRAP2. Recombinant
protein containing a conserved region of BbTRAP2 was produced in E. coli. A high
antigenicity of recombinant BbTRAP2 (rBbTRAP2) was observed with field B. bovis
infected bovine sera collected from geographically different regions of the
world. Moreover, antiserum against rBbTRAP2 specifically reacted with the
authentic protein by Western blot analysis and an indirect fluorescent antibody
test. Three bands corresponding to 104-, 76-, and 44-kDa proteins were identified
in the parasite lysates and two bands of 76- and 44-kDa proteins were detected in
the supernatant of cultivated parasites, indicating that BbTRAP2 was
proteolytically processed and shed into the culture. Apical and surface
localizations of BbTRAP2 were observed in the intracellular and extracellular
parasites, respectively, by confocal laser microscopic examination. Moreover,
native BbTRAP2 was precipitated by bovine erythrocytes, suggesting its role in
the attachment to erythrocytes. Furthermore, the specific antibody to rBbTRAP2
inhibited the growth of B. bovis in a concentration-dependent manner.
Consistently, pre-incubation of the free merozoites with the antibody to rBbTRAP2
resulted in an inhibition of the parasite invasion into host erythrocytes.
Interestingly, the antibody to rBbTRAP2 was the most inhibitive for the
parasite's growth as compared to those of a set of antisera produced against
different recombinant proteins, including merozoite surface antigen 2c (BbMSA
2c), rhoptry-associated protein 1 C-terminal (BbRAP-1CT), and spherical body
protein 1 (BbSBP-1). These results suggest that BbTRAP2 might be a potential
candidate for development of a subunit vaccine against B. bovis infection.
PMID- 24349485
TI - Hepatitis C virus infection causes iron deficiency in Huh7.5.1 cells.
AB - Patients with chronic hepatitis C virus (HCV) infection frequently develop
systemic iron overload, which exacerbates morbidity. Nevertheless, iron inhibits
HCV replication in cell culture models and thereby exerts antiviral activity. We
hypothesized that the cellular iron status is crucial for the establishment of
HCV infection. We show that HCV infection of permissive Huh7.5.1 hepatoma cells
promotes an iron deficient phenotype. Thus, HCV leads to increased iron
regulatory protein (IRP) activity, accumulation of IRP2 and suppression of
transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) in the
host. These data suggest that HCV regulates cellular iron levels to bypass iron
mediated inhibition in viral replication.
PMID- 24349484
TI - When, where and how osteoporosis-associated fractures occur: an analysis from the
Global Longitudinal Study of Osteoporosis in Women (GLOW).
AB - OBJECTIVE: To examine when, where and how fractures occur in postmenopausal
women. METHODS: We analyzed data from the Global Longitudinal Study of
Osteoporosis in Women (GLOW), including women aged >=55 years from the United
States of America, Canada, Australia and seven European countries. Women
completed questionnaires including fracture data at baseline and years 1, 2 and
3. RESULTS: Among 60,393 postmenopausal women, 4122 incident fractures were
reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and
6% hip). Hip fractures were more likely to occur in spring, with little seasonal
variation for NHNV or spine fractures. Hip fractures occurred equally inside or
outside the home, whereas 65% of NHNV fractures occurred outside and 61% of
vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and
68-83% of hip fractures among women aged <=64 to >=85 years, increasing with age.
About 45% of vertebral fractures were associated with falls in all age groups
except those >=85 years, when only 24% occurred after falling. CONCLUSION: In
this multi-national cohort, fractures occurred throughout the year, with only hip
fracture having a seasonal variation, with a higher proportion in spring. Hip
fractures occurred equally within and outside the home, spine fractures more
often in the home, and NHNV fractures outside the home. Falls were a proximate
cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture
need counseling about reducing potentially modifiable fracture risk factors,
particularly falls both inside and outside the home and during all seasons of the
year.
PMID- 24349486
TI - Effects of textured insoles on balance in people with Parkinson's disease.
AB - BACKGROUND: Degradation of the somatosensory system has been implicated in
postural instability and increased falls risk for older people and Parkinson's
disease (PD) patients. Here we demonstrate that textured insoles provide a
passive intervention that is an inexpensive and accessible means to enhance the
somatosensory input from the plantar surface of the feet. METHODS: 20 healthy
older adults (controls) and 20 participants with PD were recruited for the study.
We evaluated effects of manipulating somatosensory information from the plantar
surface of the feet using textured insoles. Participants performed standing
tests, on two different surfaces (firm and foam), under three footwear
conditions: 1) barefoot; 2) smooth insoles; and 3) textured insoles. Standing
balance was evaluated using a force plate yielding data on the range of anterior
posterior and medial-lateral sway, as well as standard deviations for anterior
posterior and medial-lateral sway. RESULTS: On the firm surface with eyes open
both the smooth and textured insoles reduced medial-lateral sway in the PD group
to a similar level as the controls. Only the textured insole decreased medial
lateral sway and medial-lateral sway standard deviation in the PD group on both
surfaces, with and without visual input. Greatest benefits were observed in the
PD group while wearing the textured insoles, and when standing on the foam
surface with eyes closed. CONCLUSIONS: Data suggested that textured insoles may
provide a low-cost means of improving postural stability in high falls-risk
groups, such as people with PD.
PMID- 24349487
TI - Is sustained virological response a marker of treatment efficacy in patients with
chronic hepatitis C viral infection with no response or relapse to previous
antiviral intervention?
AB - BACKGROUND: Randomised clinical trials (RCTs) of antiviral interventions in
patients with chronic hepatitis C virus (HCV) infection use sustained virological
response (SVR) as the main outcome. There is sparse information on long-term
mortality from RCTs. METHODS: We created a decision tree model based on a
Cochrane systematic review on interferon retreatment for patients who did not
respond to initial therapy or who relapsed following SVR. Extrapolating data to
20 years, we modelled the outcome from three scenarios: (1) observed medium-term
(5 year) annual mortality rates continue to the long term (20 years); (2) long
term annual mortality in retreatment responders falls to that of the general
population while retreatment non-responders continue at the medium-term
mortality; (3) long-term annual mortality in retreatment non-responders is the
same as control group non-responders (i.e., the increased treatment-related
medium mortality "wears off"). RESULTS: The mean differences in life expectancy
over 20 years with interferon versus control in the first, second, and third
scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23
years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The
life expectancy was always lower in the interferon group than in the control
group in scenario 1. In scenario 3, the interferon group had a longer life
expectancy than the control group only when more than 7% in the interferon group
achieved SVR. CONCLUSIONS: SVR may be a good prognostic marker but does not seem
to be a valid surrogate marker for assessing HCV treatment efficacy of interferon
retreatment. The SVR threshold at which retreatment increases life expectancy may
be different for different drugs depending upon the adverse event profile and
treatment efficacy. This has to be determined for each drug by RCTs and
appropriate modelling before SVR can be accepted as a surrogate marker.
PMID- 24349488
TI - PTEN increases autophagy and inhibits the ubiquitin-proteasome pathway in glioma
cells independently of its lipid phosphatase activity.
AB - Two major mechanisms of intracellular protein degradation, autophagy and the
ubiquitin-proteasome pathway, operate in mammalian cells. PTEN, which is
frequently mutated in glioblastomas, is a tumor suppressor gene that encodes a
dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase
class I/AKT/mTOR pathway, which is a key regulator of autophagy. Here, we
investigated in U87MG human glioma cells the role of PTEN in the regulation of
autophagy and the ubiquitin-proteasome pathway, because both are functionally
linked and are relevant in cancer progression. Since U87MG glioma cells lack a
functional PTEN, we used stable clones that express, under the control of a
tetracycline-inducible system (Tet-on), wild-type PTEN and two of its mutants,
G129E-PTEN and C124S-PTEN, which, respectively, lack the lipid phosphatase
activity only and both the lipid and the protein phosphatase activities of this
protein. Expression of PTEN in U87MG glioma cells decreased proteasome activity
and also reduced protein ubiquitination. On the contrary, expression of PTEN
increased the autophagic flux and the lysosomal mass. Interestingly, and although
PTEN negatively regulates the phosphatidylinositol 3-kinase class I/AKT/mTOR
signaling pathway by its lipid phosphatase activity, both effects in U87MG cells
were independent of this activity. These results suggest a new mTOR-independent
signaling pathway by which PTEN can regulate in opposite directions the main
mechanisms of intracellular protein degradation.
PMID- 24349489
TI - Whole-exome sequencing to identify a novel LMNA gene mutation associated with
inherited cardiac conduction disease.
AB - BACKGROUND: Inherited cardiac conduction diseases (CCD) are rare but are caused
by mutations in a myriad of genes. Recently, whole-exome sequencing has
successfully led to the identification of causal mutations for rare monogenic
Mendelian diseases. OBJECTIVE: To investigate the genetic background of a family
affected by inherited CCD. METHODS AND RESULTS: We used whole-exome sequencing to
study a Chinese family with multiple family members affected by CCD. Using the
pedigree information, we proposed a heterozygous missense mutation (c.G695T,
Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for
susceptibility to CCD in this family. The mutation is novel and is expected to
affect the conformation of the coiled-coil rod domain of LMNA according to a
structural model prediction. Its pathogenicity in lamina instability was further
verified by expressing the mutation in a cellular model. CONCLUSIONS: Our results
suggest that whole-exome sequencing is a feasible approach to identifying the
candidate genes underlying inherited conduction diseases.
PMID- 24349490
TI - Rab39a interacts with phosphatidylinositol 3-kinase and negatively regulates
autophagy induced by lipopolysaccharide stimulation in macrophages.
AB - Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation
and neuritogenesis. Here, we characterized Rab39a function in membrane
trafficking of phagocytosis and autophagy induction in macrophages. Rab39a
localized to the periphery of LAMP2-positive vesicles and showed the similar
kinetics on the phagosome to that of LAMP1. The depletion of Rab39a did not
influence the localization of LAMP2 to the phagosome, but it augments the
autophagosome formation and LC3 processing by lipopolysaccharide (LPS)
stimulation. The augmentation of autophagosome formation in Rab39a-knockdown
macrophages was suppressed by Atg5 depletion or an inhibitor for
phosphatidylinostol 3-kinase (PI3K). Immunoprecipitation analysis revealed that
Rab39a interacts with PI3K and that the amino acid residues from 34(th) to 41(st)
in Rab39a were indispensable for this interaction. These results suggest that
Rab39a negatively regulates the LPS-induced autophagy in macrophages.
PMID- 24349491
TI - Mitochondrial DNA damage via augmented oxidative stress regulates endoplasmic
reticulum stress and autophagy: crosstalk, links and signaling.
AB - Saturated free fatty acids (FFAs) have been implicated in the increase of
oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress,
autophagy, and insulin resistance (IR) observed in skeletal muscle. Previously,
we have shown that palmitate-induced mitochondrial DNA (mtDNA) damage triggers
mitochondrial dysfunction, mitochondrial reactive oxygen species (mtROS)
production, apoptosis and IR in L6 myotubes. The present study showed that
mitochondrial overexpression of human 8-oxoguanine DNA glycosylase/AP lyase
(hOGG1) decreased palmitate-induced carbonylation of proteins in mitochondria.
Additionally, we found that protection of mtDNA from palmitate-induced damage
significantly diminished markers of both ER stress and autophagy in L6 myotubes.
Moreover, we observed that the addition of ROS scavenger, N-acetylcystein (NAC),
to palmitate diminished both ER stress and autophagy markers mimicking the effect
of mitochondrial overexpression of hOGG1. This is the first study to show that
mtDNA damage is upstream of palmitate-induced ER stress and autophagy in skeletal
muscle cells.
PMID- 24349492
TI - Sleep-related declarative memory consolidation and verbal replay during sleep
talking in patients with REM sleep behavior disorder.
AB - OBJECTIVE: To determine if sleep talkers with REM sleep behavior disorder (RBD)
would utter during REM sleep sentences learned before sleep, and to evaluate
their verbal memory consolidation during sleep. METHODS: Eighteen patients with
RBD and 10 controls performed two verbal memory tasks (16 words from the Free and
Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test)
in the evening, followed by nocturnal video-polysomnography and morning recall
(night-time consolidation). In 9 patients with RBD, daytime consolidation
(morning learning/recall, evening recall) was also evaluated with the modified
Story Recall Test in a cross-over order. Two RBD patients with dementia were
studied separately. Sleep talking was recorded using video-polysomnography, and
the utterances were compared to the studied texts by two external judges.
RESULTS: Sleep-related verbal memory consolidation was maintained in patients
with RBD (+24+/-36% words) as in controls (+9+/-18%, p=0.3). The two demented
patients with RBD also exhibited excellent nighttime consolidation. The post
sleep performance was unrelated to the sleep measures (including continuity,
stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9+/-19%)
was worse than night-time consolidation (+29+/-45%, p=0.03) in the subgroup of 9
patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced
a median of 20 words, which represented 0.0003% of sleep with spoken language. A
single patient uttered a sentence that was judged to be semantically (but not
literally) related to the text learned before sleep. CONCLUSION: Verbal
declarative memory normally consolidates during sleep in patients with RBD. The
incorporation of learned material within REM sleep-associated sleep talking in
one patient (unbeknownst to himself) at the semantic level suggests a replay at a
highly cognitive creative level.
PMID- 24349493
TI - A coregulatory network of NR2F1 and microRNA-140.
AB - BACKGROUND: Both nuclear receptor subfamily 2 group F member 1 (NR2F1) and
microRNAs (miRNAs) have been shown to play critical roles in the developing and
functional inner ear. Based on previous studies suggesting interplay between
NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to
better understand the regulatory mechanisms of inner ear development and
functional maturation. RESULTS: Using a bioinformatic approach, we identified 11
potential miRNAs that might coregulate target genes with NR2F1 and analyzed their
targets and potential roles in physiology and disease. We selected 6 miRNAs to
analyze using quantitative real-time (qRT) -PCR and found that miR-140 is
significantly down-regulated by 4.5-fold (P=0.004) in the inner ear of NR2F1
knockout (Nr2f1(-/-)) mice compared to wild-type littermates but is unchanged in
the brain. Based on this, we performed chromatin-immunoprecipitation followed by
qRT-PCR and confirmed that NR2F1 directly binds and regulates both miR-140 and
Klf9 in vivo. Furthermore, we performed luciferase reporter assay and showed that
miR-140 mimic directly regulates KLF9-3'UTR, thereby establishing and validating
an example coregulatory network involving NR2F1, miR-140, and Klf9. CONCLUSIONS:
We have described and experimentally validated a novel tissue-dependent
coregulatory network for NR2F1, miR-140, and Klf9 in the inner ear and we propose
the existence of many such coregulatory networks important for both inner ear
development and function.
PMID- 24349494
TI - Apolipoprotein E gene variants on the risk of end stage renal disease.
AB - OBJECTIVE: End-stage renal disease (ESRD) is a severe health concern over the
world. Associations between apolipoprotein E (apoE) gene polymorphisms and the
risk of ESRD remained inconclusive. This study aimed to investigate the
association between apoE gene polymorphisms and ESRD susceptibility. METHODS:
Databases including PubMed, Embase, Web of Science and the Cochrane Library were
searched to find relevant studies. Meta-analysis method was used synthesize the
eligible studies. RESULTS: Sixteen pertinent case-control studies which included
3510 cases and 13924 controls were analyzed. A significant association was found
between epsilon2 allele and the ESRD risk (odds ratio (OR) = 1.30, 95% confidence
interval (CI) 1.15-1.46, P < 0.0001; I (2) = 18%, P for heterogeneity = 0.24).
The epsilon2epsilon3, epsilon2epsilon4, epsilon3epsilon3, epsilon3epsilon4,
epsilon4epsilon4, epsilon3 and epsilon4 were not associated with the
susceptibility of ESRD. In the subgroup analysis by ethnicity, there was a
statistically significant association between epsilon2epsilon3 or epsilon2 allele
and ESRD risk in East Asians (OR = 1.66, 95% CI 1.31-2.10, P < 0.0001; OR = 1.62,
95% CI 1.31-2.01, P < 0.0001, respectively), but not in Caucasians. E2 carriers
had higher plasma apoE (mean difference = 16.24 mg/L, 95% CI 7.76-24.73, P =
0.0002) than the (epsilon3 + epsilon4) carriers in patients with ESRD. The
publication bias was not significant. CONCLUSION: The epsilon2 allele of apoE
gene might increase the risk of ESRD. E2 carriers expressed higher level of
plasma apoE in patients with ESRD. More well-designed studies are needed to
confirm these associations in the future.
PMID- 24349495
TI - Expression of Panton-Valentine leukocidin mRNA among Staphylococcus aureus
isolates associates with specific clinical presentations.
AB - Panton-Valentine leukocidin (PVL; gene designation lukF/S-PV) is likely an
important virulence factor for Staphylococcus aureus (S. aureus), as qualitative
expression of the protein correlates with severity for specific clinical
presentations, including skin and soft tissue infections (SSTIs). Development of
genetic approaches for risk-assessment of patients with S. aureus infections may
prove clinically useful, and whether lukF/S-PV gene expression correlates with
specific clinical presentations for S. aureus has been largely unexplored. In the
present study, we quantified lukS-PV mRNA among 96 S. aureus isolates to
determine whether expression levels correlated with specific clinical
presentations in adults and children. Expression level of lukS-PV mRNA among
isolates from skin and soft tissue infections (SSTIs) was significantly greater
than among isolates from blood stream infection (BSIs), and expression level of
lukS-PV mRNA among BSI isolates from children was significantly greater than for
BSI isolates among adults. Moreover, expression level of lukS-PV mRNA among
community-acquired (CA) isolates was significantly greater than for hospital
acquired (HA) isolates. These data justify additional studies to determine the
potential clinical utility for lukS-PV mRNA quantification as a predictive tool
for severity of S. aureus infection.
PMID- 24349496
TI - Effects of nutritional supplementation during pregnancy on early adult disease
risk: follow up of offspring of participants in a randomised controlled trial
investigating effects of supplementation on infant birth weight.
AB - BACKGROUND: Observational evidence suggests that improving fetal growth may
improve adult health. Experimental evidence from nutritional supplementation
trials undertaken amongst pregnant women in the less developed world does not
show strong or consistent effects on adult disease risk and no trials from the
more developed world have previously been reported. OBJECTIVE: To test the
hypothesis that nutritional supplementation during pregnancy influences offspring
disease risk in adulthood. DESIGN: Clinical assessment of a range of established
diseases risk markers in young adult offspring of 283 South Asian mothers who
participated in two trials of nutritional supplementation during pregnancy
(protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity
Hospital in Birmingham UK either unselected or selected on the basis of
nutritional status. RESULTS: 236 (83%) offspring were traced and 118 (50%) of
these were assessed in clinic. Protein/energy/vitamins supplementation amongst
undernourished mothers was associated with increased infant birthweight.
Nutritional supplementation showed no strong association with any one of a
comprehensive range of markers of adult disease risk and no consistent pattern of
association with risk across markers in offspring of either unselected or
undernourished mothers. CONCLUSIONS: We found no evidence that nutritional
supplements given to pregnant women are an important influence on adult disease
risk however our study lacked power to estimate small effects. Our findings do
not provide support for a policy of nutritional supplementation for pregnant
women as an effective means to improve adult health in more developed societies.
PMID- 24349498
TI - Seasonal foraging ecology of non-migratory cougars in a system with migrating
prey.
AB - We tested for seasonal differences in cougar (Puma concolor) foraging behaviors
in the Southern Yellowstone Ecosystem, a multi-prey system in which ungulate prey
migrate, and cougars do not. We recorded 411 winter prey and 239 summer prey
killed by 28 female and 10 male cougars, and an additional 37 prey items by
unmarked cougars. Deer composed 42.4% of summer cougar diets but only 7.2% of
winter diets. Males and females, however, selected different proportions of
different prey; male cougars selected more elk (Cervus elaphus) and moose (Alces
alces) than females, while females killed greater proportions of bighorn sheep
(Ovis canadensis), pronghorn (Antilocapra americana), mule deer (Odocoileus
hemionus) and small prey than males. Kill rates did not vary by season or between
males and females. In winter, cougars were more likely to kill prey on the
landscape as: 1) elevation decreased, 2) distance to edge habitat decreased, 3)
distance to large bodies of water decreased, and 4) steepness increased, whereas
in summer, cougars were more likely to kill in areas as: 1) elevation decreased,
2) distance to edge habitat decreased, and 3) distance from large bodies of water
increased. Our work highlighted that seasonal prey selection exhibited by
stationary carnivores in systems with migratory prey is not only driven by
changing prey vulnerability, but also by changing prey abundances. Elk and deer
migrations may also be sustaining stationary cougar populations and creating
apparent competition scenarios that result in higher predation rates on migratory
bighorn sheep in winter and pronghorn in summer. Nevertheless, cougar predation
on rare ungulates also appeared to be influenced by individual prey selection.
PMID- 24349497
TI - Next generation inactivated polio vaccine manufacturing to support post polio
eradication biosafety goals.
AB - Worldwide efforts to eradicate polio caused a tipping point in polio vaccination
strategies. A switch from the oral polio vaccine, which can cause circulating and
virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is
scheduled. Moreover, a manufacturing process, using attenuated virus strains
instead of wild-type polioviruses, is demanded to enhance worldwide production of
IPV, especially in low- and middle income countries. Therefore, development of an
IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from
the current IPV production process based on wild type Salk strains, adaptations,
such as lower virus cultivation temperature, were implemented. sIPV was produced
at industrial scale followed by formulation of both plain and aluminium
adjuvanted sIPV. The final products met the quality criteria, were immunogenic in
rats, showed no toxicity in rabbits and could be released for testing in the
clinic. Concluding, sIPV was developed to manufacturing scale. The technology can
be transferred worldwide to support post polio-eradication biosafety goals.
PMID- 24349499
TI - The bZIP transcription factor Fgap1 mediates oxidative stress response and
trichothecene biosynthesis but not virulence in Fusarium graminearum.
AB - Redox sensing is of primary importance for fungi to cope with oxidant compounds
found in their environment. Plant pathogens are particularly subject to the
oxidative burst during the primary steps of infection. In the budding yeast
Saccharomyces cerevisiae, it is the transcription factor Yap1 that mediates the
response to oxidative stress via activation of genes coding for detoxification
enzymes. In the cereal pathogen Fusarium graminearum, Fgap1 a homologue of Yap1
was identified and its role was investigated. During infection, this pathogen
produces mycotoxins belonging to the trichothecenes family that accumulate in the
grains. The global regulation of toxin biosynthesis is not completely understood.
However, it is now clearly established that an oxidative stress activates the
production of toxins by F. graminearum. The involvement of Fgap1 in this
activation was investigated. A deleted mutant and a strain expressing a truncated
constitutive form of Fgap1 were constructed. None of the mutants was affected in
pathogenicity. The deleted mutant showed higher level of trichothecenes
production associated with overexpression of Tri genes. Moreover activation of
toxin accumulation in response to oxidative stress was no longer observed.
Regarding the mutant with the truncated constitutive form of Fgap1, toxin
production was strongly reduced. Expression of oxidative stress response genes
was not activated in the deleted mutant and expression of the gene encoding the
mitochondrial superoxide dismutase MnSOD1 was up-regulated in the mutant with the
truncated constitutive form of Fgap1. Our results demonstrate that Fgap1 plays a
key role in the link between oxidative stress response and F. graminearum
secondary metabolism.
PMID- 24349500
TI - KIR, HLA, and IL28B variant predict response to antiviral therapy in genotype 1
chronic hepatitis C patients in Japan.
AB - Natural killer cell responses play a crucial role in virus clearance by the
innate immune system. Although the killer immunoglobulin-like receptor (KIR) in
combination with its cognate human leukocyte antigen (HLA) ligand, especially
KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous
clearance of hepatitis C virus (HCV) infection in Caucasians, these innate
immunity genes have not been fully clarified in Japanese patients. We therefore
investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic
variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1
patients who underwent pegylated-interferon-alpha2b (PEG-IFN) and ribavirin
therapy. HLA-Bw4 was significantly associated with a sustained virological
response (SVR) to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the
centromeric A/A haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates
were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR =
0.30, and P = 0.025; OR = 0.32, respectively). Multivariate logistic regression
analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87,
95% confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR =
0.24, 95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37
- 8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI =
1.35 - 8.16) as independent predictive factors of an SVR. We observed a
significant association between the combination of IL28B TT genotype and KIR3DL1
HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with KIR2DL2-HLA-C1
was related to a non-response (P = 0.0067). In conclusion, combinations of
KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are
predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients
infected with genotype 1b HCV.
PMID- 24349501
TI - Effect of caffeine-containing beverage consumption on serum alanine
aminotransferase levels in patients with chronic hepatitis C virus infection: a
hospital-based cohort study.
AB - INTRODUCTION: To date, there have been no prospective studies examining the
effect of coffee consumption on serum alanine aminotransferase (ALT) level among
individuals infected with the hepatitis C virus (HCV). We conducted a hospital
based cohort study among patients with chronic HCV infection to assess an
association between baseline coffee consumption and subsequent ALT levels for 12
months. MATERIALS AND METHODS: From 1 August 2005 to 31 July 2006, total 376 HCV
RNA positive patients were recruited. A baseline questionnaire elicited
information on the frequency of coffee consumption and other caffeine-containing
beverages. ALT level as a study outcome was followed through the patients'
medical records during 12 months. The association between baseline beverage
consumption and subsequent ALT levels was evaluated separately among patients
with baseline ALT levels within normal range (<=45 IU/L) and among those with
higher ALT levels (>45 IU/L). RESULTS: Among 229 patients with baseline ALT
levels within normal range, 186 (81%) retained normal ALT levels at 12 months
after recruitment. Daily drinkers of filtered coffee were three times more likely
to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However,
decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal
ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147
patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of
>=20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a
significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in
decaffeinated coffee drinkers, OR could not be calculated because no patients had
ALT reduction. CONCLUSION: Among patients with chronic HCV infection, daily
consumption of filtered coffee may have a beneficial effect on the stabilization
of ALT levels.
PMID- 24349502
TI - New rRNA gene-based phylogenies of the Alphaproteobacteria provide perspective on
major groups, mitochondrial ancestry and phylogenetic instability.
AB - Bacteria in the class Alphaproteobacteria have a wide variety of lifestyles and
physiologies. They include pathogens of humans and livestock, agriculturally
valuable strains, and several highly abundant marine groups. The ancestor of
mitochondria also originated in this clade. Despite significant effort to
investigate the phylogeny of the Alphaproteobacteria with a variety of methods,
there remains considerable disparity in the placement of several groups. Recent
emphasis on phylogenies derived from multiple protein-coding genes remains
contentious due to disagreement over appropriate gene selection and the potential
influences of systematic error. We revisited previous investigations in this area
using concatenated alignments of the small and large subunit (SSU and LSU) rRNA
genes, as we show here that these loci have much lower GC bias than whole
genomes. This approach has allowed us to update the canonical 16S rRNA gene tree
of the Alphaproteobacteria with additional important taxa that were not
previously included, and with added resolution provided by concatenating the SSU
and LSU genes. We investigated the topological stability of the
Alphaproteobacteria by varying alignment methods, rate models, taxon selection
and RY-recoding to circumvent GC content bias. We also introduce RYMK-recoding
and show that it avoids some of the information loss in RY-recoding. We
demonstrate that the topology of the Alphaproteobacteria is sensitive to
inclusion of several groups of taxa, but it is less affected by the choice of
alignment and rate methods. The majority of topologies and comparative results
from Approximately Unbiased tests provide support for positioning the
Rickettsiales and the mitochondrial branch within a clade. This composite clade
is a sister group to the abundant marine SAR11 clade (Pelagibacterales).
Furthermore, we add support for taxonomic assignment of several recently
sequenced taxa. Accordingly, we propose three subclasses within the
Alphaproteobacteria: the Caulobacteridae, the Rickettsidae, and the
Magnetococcidae.
PMID- 24349503
TI - Validation and calibration of a computer simulation model of pediatric HIV
infection.
AB - BACKGROUND: Computer simulation models can project long-term patient outcomes and
inform health policy. We internally validated and then calibrated a model of HIV
disease in children before initiation of antiretroviral therapy to provide a
framework against which to compare the impact of pediatric HIV treatment
strategies. METHODS: We developed a patient-level (Monte Carlo) model of HIV
progression among untreated children <5 years of age, using the Cost
Effectiveness of Preventing AIDS Complications model framework: the CEPAC
Pediatric model. We populated the model with data on opportunistic infection and
mortality risks from the International Epidemiologic Database to Evaluate AIDS
(IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/month) from
the Women and Infants' Transmission Study (WITS). We internally validated the
model by varying WITS-derived CD4% data, comparing the corresponding model
generated survival curves to empirical survival curves from IeDEA, and
identifying best-fitting parameter sets as those with a root-mean square error
(RMSE) <0.01. We then calibrated the model to other African settings by
systematically varying immunologic and HIV mortality-related input parameters.
Model-generated survival curves for children aged 0-60 months were compared,
again using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African
children. RESULTS: In internal validation analyses, model-generated survival
curves fit IeDEA data well; modeled and observed survival at 16 months of age
were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4%
parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4%
was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages
>3 months). In calibration analyses, increases in IeDEA-derived mortality risks
were necessary to fit UNAIDS survival data. CONCLUSIONS: The CEPAC-Pediatric
model performed well in internal validation analyses. Increases in modeled
mortality risks required to match UNAIDS data highlight the importance of pre
enrollment mortality in many pediatric cohort studies.
PMID- 24349505
TI - Long-term functional dynamics of an aphidophagous coccinellid community remain
unchanged despite repeated invasions.
AB - Aphidophagous coccinellids (ladybeetles) are important providers of herbivore
suppression ecosystem services. In the last 30 years, the invasion of exotic
coccinellid species, coupled with observed declines in native species, has led to
considerable interest in the community dynamics and ecosystem function of this
guild. Here we examined a 24-year dataset of coccinellid communities in nine
habitats in southwestern Michigan for changes in community function in response
to invasion. Specifically we analyzed their temporal population dynamics and
species diversity, and we modeled the community's potential to suppress pests.
Abundance of coccinellids varied widely between 1989 and 2012 and became
increasingly exotic-dominated. More than 71% of 57,813 adult coccinellids
captured over the 24-year study were exotic species. Shannon diversity increased
slightly over time, but herbivore suppression potential of the community remained
roughly constant over the course of the study. However, both Shannon diversity
and herbivore suppression potential due to native species declined over time in
all habitats. The relationship between Shannon diversity and herbivore
suppression potential varied with habitat type: a positive relationship in forest
and perennial habitats, but was uncorrelated in annual habitats. This trend may
have been because annual habitats were dominated by a few, highly voracious
exotic species. Our results indicated that although the composition of the
coccinellid community in southwestern Michigan has changed dramatically in the
past several decades, its function has remained relatively unchanged in both
agricultural and natural habitats. While this is encouraging from the perspective
of pest management, it should be noted that losses of one of the dominant exotic
coccinellids could result in a rapid decline in pest suppression services if the
remaining community is unable to respond.
PMID- 24349504
TI - Dietary BMAA exposure in an amyotrophic lateral sclerosis cluster from southern
France.
AB - BACKGROUND: Dietary exposure to the cyanotoxin BMAA is suspected to be the cause
of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and
North America, this toxin has been identified in the marine environment of
amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures
have been described. OBJECTIVES: We aimed at identifying cluster(s) of
amyotrophic lateral sclerosis in the Herault district, a coastal district from
Southern France, and to search, in the identified area(s), for the existence of a
potential dietary source of BMAA. METHODS: A spatio-temporal cluster analysis was
performed in the district, considering all incident amyotrophic lateral sclerosis
cases identified from 1994 to 2009 by our expert center. We investigated the
cluster area with serial collections of oysters and mussels that were
subsequently analyzed blind for BMAA concentrations. RESULTS: We found one
significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the
Thau lagoon, the most important area of shellfish production and consumption
along the French Mediterranean coast. BMAA was identified in mussels (1.8 ug/g to
6.0 ug/g) and oysters (0.6 ug/g to 1.6 ug/g). The highest concentrations of BMAA
were measured during summer when the highest picocyanobacteria abundances were
recorded. CONCLUSIONS: While it is not possible to ascertain a direct link
between shellfish consumption and the existence of this ALS cluster, these
results add new data to the potential association of BMAA with sporadic
amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.
PMID- 24349506
TI - Aristolochic acid causes albuminuria by promoting mitochondrial DNA damage and
dysfunction in podocyte.
AB - Aristolochic acid nephropathy, initially found in patients intaking of slimming
herbs containing aristolochic acid (AA), was previously considered as a
progressive renal interstitial fibrosis and urothelial malignancy. However, the
presence of albuminuria in some patients with AAN suggests that AA may also
damage the glomerular filtration barrier. In this study, mice AAN model was
generated by daily administration of aristolochic acid I sodium salt
intraperitoneally at a dose of 6 mg/kg body weight for 3 days. All of the mice
developed heavy albuminuria at day 3 and 7 after receiving AA. In the mice
received AA, morphologic change of glomeruli was minor under light microscopy but
podocyte foot-process effacement was evident under electron microscopy. In
mitochondria isolated from kidney, prominent mitochondrial DNA (mtDNA) damage was
accompanied with marked decrease of mtDNA copy number and mitochondrial protein
expression level. Similar to those in vivo results, AA treatment impaired the
filtration barrier function of cultured podocytes. AA promoted mtDNA damage,
decreased mtDNA copy number and mitochondrial protein expression in cultured
podocytes. In addition, AA treatment also decreased ATP content, oxygen
consumption rate and mitochondrial membrane potential as well as increased
cellular reactive oxygen species in cultured podocytes. This study highlighted
that AA could induce podocyte damage and albuminuria, which may be mediated by
promoting mtDNA damage and mitochondrial dysfunction in podocytes.
PMID- 24349507
TI - Influence of the angiotensin converting enzyme insertion or deletion genetic
variant and coronary restenosis risk: evidence based on 11,193 subjects.
AB - The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin
converting enzyme is a controversial risk factor for restenosis after
percutaneous transluminal coronary angioplasties (PTCA) in patients. Genetic
association studies can be problematic to reproduce due to insufficient power,
phenotypic heterogeneity, population stratification, small effect of the variant
and even publication biases. To derive a more precise estimation of the
relationship as well as to quantify the between-study heterogeneity and potential
bias, a meta-analysis including 11,193 patients from 33 published cohort studies
was performed. In a combined analysis, the summary per-allele odds ratio for
restenosis was 1.31 (95% CI: 1.08-1.58, P = 0.006), and 1.22 (95% CI: 0.95-1.56,
P = 0.12), for PTCA-stent and PTCA-balloon, respectively. In the subgroup
analysis by ethnicity, significantly increased restenosis risks after PTCA-stent
were found in Asians for the polymorphism; whereas no significant associations
were found among Caucasians. As for restenosis risks after PTCA-balloon, no
evidence of any gene-disease association was obtained in the stratified analyses
according to ethnicity and study size. In conclusion, this meta-analysis
demonstrated that the DD homozygous of ACE I/D polymorphism was significantly
associated with elevated restenosis susceptibility after PTCA-stent among Asian
populations.
PMID- 24349509
TI - Cadmium induces liver cell apoptosis through caspase-3A activation in purse red
common carp (Cyprinus carpio).
AB - Caspase-3, the essential effector caspase, plays a pivotal role during caspase
dependent apoptosis. In this study, we isolated and characterized caspase-3A gene
from common carp. The common carp caspase-3A comprising 273 amino acids showed
71.8% sequence similarity and 59.3% sequence identity to human caspase-3. It
exhibited an evolutionarily conserved structure of mammalian caspase-3 genes,
including a pro-domain, a large subunit, a small subunit and other motifs such as
the pentapeptide active-site motif (QACRG) and the putative cleavage sites at the
aspartic acids. Phylogenetic analysis demonstrated that common carp caspase-3A
formed a clade with cyprinid fish caspase-3. To assess whether caspase-3A is
involved in cadmium (Cd)-induced cell apoptosis in common carp, a Cd exposure
experiment was performed. TUNEL analysis showed that Cd triggered liver cell
apoptosis; caspase-3A activity was markedly increased; its proenzyme level was
significantly decreased, and the levels of its cleaved forms were markedly
increased. However, real-time quantitative PCR analysis revealed that the mRNA
transcript level of caspase-3A was not significantly elevated. Immunoreactivities
were observed in the cytoplasm of hepatocytes by immunohistochemical detection.
The findings indicates that Cd can trigger liver cell apoptosis through the
activation of caspase-3A. Caspase-3A may play an essential role in Cd-induced
apoptosis.
PMID- 24349510
TI - Sputum microbiota associated with new, recurrent and treatment failure
tuberculosis.
AB - Microbiota have recently been shown to be associated with many disease
conditions. However, the microbiota associated with tuberculosis (TB) infection,
recurrence and treatment outcome have not been systematically characterized.
Here, we used high throughput 16S RNA sequencing to analyze the sputum microbiota
associated with Mycobacterium tuberculosis infection and also to identify the
microorganisms associated with different outcomes of TB treatment. We recruited
25 new TB patients, 30 recurrent TB patients and 20 TB patients with treatment
failure, as well as 20 healthy controls. Streptococcus, Gramulicatella and
Pseudomonas were more abundant in TB patients while Prevotella, Leptotrichia,
Treponema, Catonella and Coprococcus were less abundant in TB patients than in
the healthy controls. We found reduced frequency and abundance of some genera
such as Bulleidia and Atopobium in recurrent TB patients compared with those in
new TB patients. In addition, the ratio of Pseudomonas / Mycobacterium in
recurrent TB was higher than that in new TB while the ratio of Treponema /
Mycobacterium in recurrent TB was lower than that in new TB, indicating that
disruption of these bacteria may be a risk factor of TB recurrence. Furthermore,
Pseudomonas was more abundant and more frequently present in treatment failure
patients than in cured new patients, and the ratio of Pseudomonas / Mycobacterium
in treatment failure was higher than that in new TB. Our data suggest that the
presence of certain bacteria and the disorder of lung microbiota may be
associated with not only onset of TB but also its recurrence and treatment
failure. These findings indicate that lung microbiota may play a role in
pathogenesis and treatment outcome of TB and may need to be taken into
consideration for improved treatment and control of TB in the future.
PMID- 24349508
TI - From knock-out phenotype to three-dimensional structure of a promising antibiotic
target from Streptococcus pneumoniae.
AB - Given the rise in drug-resistant Streptococcus pneumoniae, there is an urgent
need to discover new antimicrobials targeting this pathogen and an equally urgent
need to characterize new drug targets. A promising antibiotic target is
dihydrodipicolinate synthase (DHDPS), which catalyzes the rate-limiting step in
lysine biosynthesis. In this study, we firstly show by gene knock out studies
that S. pneumoniae (sp) lacking the DHDPS gene is unable to grow unless
supplemented with lysine-rich media. We subsequently set out to characterize the
structure, function and stability of the enzyme drug target. Our studies show
that sp-DHDPS is folded and active with a k(cat) = 22 s(-1), K(M)(PYR) = 2.55 +/-
0.05 mM and K(M)(ASA) = 0.044 +/- 0.003 mM. Thermal denaturation experiments
demonstrate sp-DHDPS exhibits an apparent melting temperature (T(M)(app)) of 72
degrees C, which is significantly greater than Escherichia coli DHDPS (Ec-DHDPS)
(T(M)(app) = 59 degrees C). Sedimentation studies show that sp-DHDPS exists in a
dimer-tetramer equilibrium with a K(D)(4->2) = 1.7 nM, which is considerably
tighter than its E. coli ortholog (K(D)(4->2) = 76 nM). To further characterize
the structure of the enzyme and probe its enhanced stability, we solved the high
resolution (1.9 A) crystal structure of sp-DHDPS (PDB ID 3VFL). The enzyme is
tetrameric in the crystal state, consistent with biophysical measurements in
solution. Although the sp-DHDPS and Ec-DHDPS active sites are almost identical,
the tetramerization interface of the s. pneumoniae enzyme is significantly
different in composition and has greater buried surface area (800 A(2)) compared
to its E. coli counterpart (500 A(2)). This larger interface area is consistent
with our solution studies demonstrating that sp-DHDPS is considerably more
thermally and thermodynamically stable than Ec-DHDPS. Our study describe for the
first time the knock-out phenotype, solution properties, stability and crystal
structure of DHDPS from S. pneumoniae, a promising antimicrobial target.
PMID- 24349511
TI - Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity
in C. elegans.
AB - An expansion of the hexanucleotide GGGGCC repeat in the first intron of C9ORF72
gene was recently linked to amyotrophic lateral sclerosis. It is not known if the
mutation results in a gain of function, a loss of function or if, perhaps both
mechanisms are linked to pathogenesis. We generated a genetic model of ALS to
explore the biological consequences of a null mutation of the Caenorhabditis
elegans C9ORF72 orthologue, F18A1.6, also called alfa-1. alfa-1 mutants displayed
age-dependent motility defects leading to paralysis and the specific degeneration
of GABAergic motor neurons. alfa-1 mutants showed differential susceptibility to
environmental stress where osmotic stress provoked neurodegeneration. Finally, we
observed that the motor defects caused by loss of alfa-1 were additive with the
toxicity caused by mutant TDP-43 proteins, but not by the mutant FUS proteins.
These data suggest that a loss of alfa-1/C9ORF72 expression may contribute to
motor neuron degeneration in a pathway associated with other known ALS genes.
PMID- 24349512
TI - Involvement of autonomic nervous activity changes in gastroesophageal reflux in
neonates during sleep and wakefulness.
AB - BACKGROUND: It has been suggested that disturbed activity of the autonomic
nervous system is one of the factors involved in gastroesophageal reflux (GER) in
adults. We sought to establish whether transient ANS dysfunction (as assessed by
heart rate variability) is associated with the occurrence of GER events in
neonates during sleep and wakefulness. METHODS: Nineteen neonates with suspected
GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal
multichannel impedance-pH monitoring. We compared changes in HRV parameters
during three types of periods (control and prior to and during reflux) with
respect to the vigilance state. RESULTS: The vigilance state influenced the
distribution of GER events (P<0.001), with 53.4% observed during wakefulness,
37.6% observed during active sleep and only 9% observed during quiet sleep. A
significant increase in the sympathovagal ratio (+32%, P=0.013) was observed in
the period immediately prior to reflux (due to a 15% reduction in parasympathetic
activity (P=0.017)), relative to the control period. This phenomenon was observed
during both wakefulness and active sleep. CONCLUSION: Our results showed that GER
events were preceded by a vigilance-state-independent decrease in parasympathetic
tone. This suggests that a pre-reflux change in ANS activity is one of the
factors contributing to the mechanism of reflux in neonates.
PMID- 24349513
TI - Early transcriptional response of soybean contrasting accessions to root
dehydration.
AB - Drought is a significant constraint to yield increase in soybean. The early
perception of water deprivation is critical for recruitment of genes that promote
plant tolerance. DeepSuperSAGE libraries, including one control and a bulk of six
stress times imposed (from 25 to 150 min of root dehydration) for drought
tolerant and sensitive soybean accessions, allowed to identify new molecular
targets for drought tolerance. The survey uncovered 120,770 unique transcripts
expressed by the contrasting accessions. Of these, 57,610 aligned with known cDNA
sequences, allowing the annotation of 32,373 unitags. A total of 1,127 unitags
were up-regulated only in the tolerant accession, whereas 1,557 were up-regulated
in both as compared to their controls. An expression profile concerning the most
representative Gene Ontology (GO) categories for the tolerant accession revealed
the expression "protein binding" as the most represented for "Molecular
Function", whereas CDPK and CBL were the most up-regulated protein families in
this category. Furthermore, particular genes expressed different isoforms
according to the accession, showing the potential to operate in the distinction
of physiological behaviors. Besides, heat maps comprising GO categories related
to abiotic stress response and the unitags regulation observed in the expression
contrasts covering tolerant and sensitive accessions, revealed the unitags
potential for plant breeding. Candidate genes related to "hormone response" (LOX,
ERF1b, XET), "water response" (PUB, BMY), "salt stress response" (WRKY, MYB) and
"oxidative stress response" (PER) figured among the most promising molecular
targets. Additionally, nine transcripts (HMGR, XET, WRKY20, RAP2-4, EREBP, NAC3,
PER, GPX5 and BMY) validated by RT-qPCR (four different time points) confirmed
their differential expression and pointed that already after 25 minutes a
transcriptional reorganization started in response to the new condition, with
important differences between both accessions.
PMID- 24349515
TI - Alterations in white matter microstructure as vulnerability factors and acquired
signs of traffic accident-induced PTSD.
AB - It remains unclear whether white matter (WM) changes found in post-traumatic
stress disorder (PTSD) patients are stress-induced or precursors for
vulnerability. The current study aimed to identify susceptibility factors
relating to the development of PTSD and to examine the ability of these factors
to predict the course of longitudinal PTSD. Sixty two victims who had experienced
traffic accidents underwent diffusion tensor imaging using a 3.0T MRI system
within 2 days after their accidents. Of these, 21 were diagnosed with PTSD at 1
or 6 months using the Clinician-Administered Ptsd Scale (CAPS). Then, 11 trauma
exposed victims with PTSD underwent the second MRI scan. Compared with the
victims without PTSD, the victims with PTSD showed decreased fractional
anisotropy (FA) in WM of the anterior cingulate cortex, ventromedial prefrontal
cortex (vmPFC), temporal lobes and midbrain, and increased mean diffusivity (MD)
in the vmPFC within 2 days after the traumatic event. Importantly, decreased FA
of the vmPFC in the acute phase predicted greater future CAPS scores. In
addition, we found decreased FA in the insula in the follow-up scan in the
victims with PTSD, which correlated with the decreased FA of the vmPFC in their
baseline scan. These results suggested that the WM might have changed within 2
days after the traumatic event in the individuals who would later develop PTSD.
Furthermore, decreased FA of the vmPFC could be a possible vulnerability marker
predicting future development of PTSD and may provide an outcome prediction of
the acquired signs.
PMID- 24349516
TI - Autophagy in the human placenta throughout gestation.
AB - BACKGROUND: Autophagy has been reported to be essential for pre-implantation
development and embryo survival. However, its role in placental development and
regulation of autophagy during pregnancy remain unclear. The aims of this study
were to (1) study autophagy by characterizing changes in levels of beclin-1,
DRAM, and LC3B in human placenta throughout gestation; (2) determine whether
autophagy is involved in regulation of trophoblast invasion in JEG-3 cells (a
choriocarcinoma cell line); (3) examine the effects of reduced oxygen and glucose
on the autophagic changes; and (4) investigate the effect of reoxygenation and
supplementation of glucose after oxygen-glucose deprivation (OGD) on the
autophagic changes in primary cytotrophoblasts obtained from normal term
pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 40 placental samples
representing different gestational stages showed (1) no significant differences
in beclin-1, DRAM, and LC3B-II levels in placentas between early and mid
gestation, and late gestation with vaginal delivery; (2) placentas from late
gestation with cesarean section had lower levels of LC3B-II compared to early and
mid-gestation, and late gestation with vaginal delivery; levels of DRAM were also
lower compared to placentas from early and mid-gestation; and (3) using explant
cultures, villous tissues from early and late gestation had similar rates of
autophagic flux under physiological oxygen concentrations. Knockdown of BECN1,
DRAM, and LC3B had no effects on viability and invasion activity of JEG-3 cells.
On the other hand, OGD caused a significant increase in the levels of LC3B-II in
primary cytotrophoblasts, while re-supplementation of oxygen and glucose reduced
these changes. Furthermore, there were differential changes in levels of beclin
1, DRAM, and LC3B-II in response to changes in oxygen and glucose levels.
CONCLUSIONS/SIGNIFICANCE: Our results indicate that autophagy is involved in
development of the human placenta and that changes in oxygen and glucose levels
participate in regulation of autophagic changes in cytotrophoblast cells.
PMID- 24349514
TI - MicroRNA-494, upregulated by tumor necrosis factor-alpha, desensitizes insulin
effect in C2C12 muscle cells.
AB - Chronic inflammation is fundamental for the induction of insulin resistance in
the muscle tissue of vertebrates. Although several miRNAs are thought to be
involved in the development of insulin resistance, the role of miRNAs in the
association between inflammation and insulin resistance in muscle tissue is
poorly understood. Herein, we investigated the aberrant expression of miRNAs by
conducting miRNA microarray analysis of TNF-alpha-treated mouse C2C12 myotubes.
We identified two miRNAs that were upregulated and six that were downregulated by
a >1.5-fold change compared to normal cells. Among the findings, qRT-PCR analysis
confirmed that miR-494 is consistently upregulated by TNF-alpha-induced
inflammation. Overexpression of miR-494 in CHO(IR/IRS1) and C2C12 myoblasts
suppressed insulin action by down-regulating phosphorylations of GSK-3alpha/beta,
AS160 and p70S6K, downstream of Akt. Moreover, overexpression of miR-494 did not
regulate TNF-alpha-mediated inflammation . Among genes bearing the seed site for
miR-494, RT-PCR analysis showed that the expression of Stxbp5, an inhibitor of
glucose transport, was downregulated following miR-494 inhibition. In contrast,
the expression of PTEN decreased in the cells analyzed, thus showing that both
positive and negative regulators of insulin action may be simultaneously
controlled by miR-494. To investigate the overall effect of miR-494 on insulin
signaling, we performed a PCR array analysis containing 84 genes related to the
insulin signaling pathway, and we observed that 25% of genes were downregulated
(P<0.05) and 11% were upregulated (P<0.05). These results confirm that miR-494
might contribute to insulin sensitivity by positive and negative regulation of
the expression of diverse genes. Of note, PCR array data showed downregulation of
Slc2A4, a coding gene for Glut4. Altogether, the present study concludes that the
upregulation of miR-494 expression by TNF-alpha-mediated inflammation exacerbates
insulin resistance. Therefore, we suggest that miR-494 could prove an important
target for the diagnosis and therapy of inflammation-mediated insulin resistance
in muscle.
PMID- 24349517
TI - Edwardsiella andrillae, a new species of sea anemone from Antarctic ice.
AB - Exploration of the lower surface of the Ross Ice Shelf in Antarctica by the
Submersible Capable of under-Ice Navigation and Imaging (SCINI) remotely operated
vehicle discovered a new species of sea anemone living in this previously
undocumented ecosystem. This discovery was a significant outcome of the Coulman
High Project's geophysical and environmental fieldwork in 2010-2011 as part of
the ANDRILL (ANtarctic geologic DRILLing) program. Edwardsiella andrillae n. sp.,
lives with most of its column in the ice shelf, with only the tentacle crown
extending into the seawater below. In addition to being the only Antarctic
representative of the genus, Edwardsiella andrillae is distinguished from all
other species of the genus in the number of tentacles and in the size and
distribution of cnidae. The anatomy and histology of Edwardsiella andrillae
present no features that explain how this animal withstands the challenges of
life in such an unusual habitat.
PMID- 24349518
TI - Alcohol, hospital discharge, and socioeconomic risk factors for default from
multidrug resistant tuberculosis treatment in rural South Africa: a retrospective
cohort study.
AB - BACKGROUND: Default from multidrug-resistant tuberculosis (MDR-TB) treatment
remains a major barrier to cure and epidemic control. We sought to identify
patient risk factors for default from MDR-TB treatment and high-risk time periods
for default in relation to hospitalization and transition to outpatient care.
METHODS: We retrospectively analyzed a cohort of 225 patients who initiated MDR
TB treatment between 2007 through 2010 at a rural TB hospital in the Western Cape
Province, South Africa. RESULTS: Fifty percent of patients were cured or
completed treatment, 27% defaulted, 14% died, 4% failed treatment, and 5%
transferred out. Recent alcohol use was common (63% of patients). In
multivariable proportional hazards regression, older age (hazard ratio [HR]= 0.97
[95% confidence interval 0.94-0.99] per year of greater age), formal housing
(HR=0.38 [0.19-0.78]), and steady employment (HR=0.41 [0.19-0.90]) were
associated with decreased risk of default, while recent alcohol use (HR=2.1 [1.1
4.0]), recent drug use (HR=2.0 [1.0-3.6]), and Coloured (mixed ancestry)
ethnicity (HR=2.3 [1.1-5.0]) were associated with increased risk of default
(P<0.05). Defaults occurred throughout the first 18 months of the two-year
treatment course but were especially frequent among alcohol users after discharge
from the initial four-to-five-month in-hospital phase of treatment, with the
highest default rates occurring among alcohol users within two months of
discharge. Default rates during the first two months after discharge were also
elevated for patients who received care from mobile clinics. CONCLUSIONS: Among
patients who were not cured or did not complete MDR-TB treatment, the majority
defaulted from treatment. Younger, economically-unstable patients and alcohol and
drug users were particularly at risk. For alcohol users as well as mobile-clinic
patients, the early outpatient treatment phase is a high-risk period for default
that could be targeted in efforts to increase treatment completion rates.
PMID- 24349520
TI - Quantifying the impact of woodpecker predation on population dynamics of the
emerald ash borer (Agrilus planipennis).
AB - The emerald ash borer (EAB), Agrilus planipennis, is an invasive beetle that has
killed millions of ash trees (Fraxinus spp.) since it was accidentally introduced
to North America in the 1990s. Understanding how predators such as woodpeckers
(Picidae) affect the population dynamics of EAB should enable us to more
effectively manage the spread of this beetle, and toward this end we combined two
experimental approaches to elucidate the relative importance of woodpecker
predation on EAB populations. First, we examined wild populations of EAB in ash
trees in New York, with each tree having a section screened to exclude
woodpeckers. Second, we established experimental cohorts of EAB in ash trees in
Maryland, and the cohorts on half of these trees were caged to exclude
woodpeckers. The following spring these trees were debarked and the fates of the
EAB larvae were determined. We found that trees from which woodpeckers were
excluded consistently had significantly lower levels of predation, and that
woodpecker predation comprised a greater source of mortality at sites with a more
established wild infestation of EAB. Additionally, there was a considerable
difference between New York and Maryland in the effect that woodpecker predation
had on EAB population growth, suggesting that predation alone may not be a
substantial factor in controlling EAB. In our experimental cohorts we also
observed that trees from which woodpeckers were excluded had a significantly
higher level of parasitism. The lower level of parasitism on EAB larvae found
when exposed to woodpeckers has implications for EAB biological control,
suggesting that it might be prudent to exclude woodpeckers from trees when
attempting to establish parasitoid populations. Future studies may include
utilizing EAB larval cohorts with a range of densities to explore the functional
response of woodpeckers.
PMID- 24349519
TI - Proteomic analysis and qRT-PCR verification of temperature response to
Arthrospira (Spirulina) platensis.
AB - Arthrospira (Spirulina) platensis (ASP) is a representative filamentous, non-N2
fixing cyanobacterium that has great potential to enhance the food supply and
possesses several valuable physiological features. ASP tolerates high and low
temperatures along with highly alkaline and salty environments, and can strongly
resist oxidation and irradiation. Based on genomic sequencing of ASP, we compared
the protein expression profiles of this organism under different temperature
conditions (15 degrees C, 35 degrees Cand 45 degrees C) using 2-DE and peptide
mass fingerprinting techniques. A total of 122 proteins having a significant
differential expression response to temperature were retrieved. Of the positively
expressed proteins, the homologies of 116 ASP proteins were found in Arthrospira
(81 proteins in Arthrospira platensis str. Paraca and 35 in Arthrospira maxima CS
328). The other 6 proteins have high homology with other microorganisms. We
classified the 122 differentially expressed positive proteins into 14 functions
using the COG database, and characterized their respective KEGG metabolism
pathways. The results demonstrated that these differentially expressed proteins
are mainly involved in post-translational modification (protein turnover,
chaperones), energy metabolism (photosynthesis, respiratory electron transport),
translation (ribosomal structure and biogenesis) and carbohydrate transport and
metabolism. Others proteins were related to amino acid transport and metabolism,
cell envelope biogenesis, coenzyme metabolism and signal transduction mechanisms.
Results implied that these proteins can perform predictable roles in rendering
ASP resistance against low and high temperatures. Subsequently, we determined the
transcription level of 38 genes in vivo in response to temperature and identified
them by qRT-PCR. We found that the 26 differentially expressed proteins,
representing 68.4% of the total target genes, maintained consistency between
transcription and translation levels. The remaining 12 genes showed inconsistent
protein expression with transcription level and accounted for 31.6% of the total
target genes.
PMID- 24349521
TI - Population genetic studies revealed local adaptation in a high gene-flow marine
fish, the small yellow croaker (Larimichthys polyactis).
AB - The genetic differentiation of many marine fish species is low. Yet local
adaptation may be common in marine fish species as the vast and changing marine
environment provides more chances for natural selection. Here, we used anonymous
as well as known protein gene linked microsatellites and mitochondrial DNA to
detect the population structure of the small yellow croaker (Larimichthys
polyactis) in the Northwest Pacific marginal seas. Among these loci, we detected
at least two microsatellites, anonymous H16 and HSP27 to be clearly under
diversifying selection in outlier tests. Sequence cloning and analysis revealed
that H16 was located in the intron of BAHCC1 gene. Landscape genetic analysis
showed that H16 mutations were significantly associated with temperature, which
further supported the diversifying selection at this locus. These marker types
presented different patterns of population structure: (i) mitochondrial DNA
phylogeny showed no evidence of genetic divergence and demonstrated only one
glacial linage; (ii) population differentiation using putatively neutral
microsatellites presented a pattern of high gene flow in the L. polyactis. In
addition, several genetic barriers were identified; (iii) the population
differentiation pattern revealed by loci under diversifying selection was rather
different from that revealed by putatively neutral loci. The results above
suggest local adaptation in the small yellow croaker. In summary, population
genetic studies based on different marker types disentangle the effects of
demographic history, migration, genetic drift and local adaptation on population
structure and also provide valuable new insights for the design of management
strategies in L. polyactis.
PMID- 24349522
TI - Imaging evidence of diabetic choroidopathy in vivo: angiographic pathoanatomy and
choroidal-enhanced depth imaging.
AB - PURPOSE: To describe the pathoanatomy of diabetic choroidopathy (DC) in pre
diagnosed diabetic retinopathy (DR) cases and to provide angiographic and optical
evidence for DC using indocyanine green angiography (ICGA) and enhanced depth
imaging spectral-domain optical coherence tomography (EDI SD-OCT). METHODS: A
retrospective analysis of 80 eyes from 40 DR patients was conducted. In Group
One, choroidal vascular abnormalities were evaluated by comparing angiographic
findings from simultaneous ICGA with those from fundus fluorescein angiography
(FFA). In Group Two, EDI SD-OCT was used to evaluate the subfoveal choroidal
thickness (SFCT) and define the choroid boundary in order to acquire the
bilateral and symmetric choroidal area (CA). Data were then analyzed by Image Pro
Plus 6.0. RESULTS: In Group One, choroidal abnormalities that were evident using
ICGA but not FFA included early hypofluorescent spots in 47 eyes (75.81%), late
hyperfluorescent spots in 37 eyes (59.68%), and late choroidal non-perfusion
regions in 32 eyes (51.61%). In particular, a significant difference between
proliferative DR (PDR) in 17 of 23 eyes (73.91%) and non-PDR in 16 of 39 eyes
(41.03%) was observed in late choroidal non-perfusion regions. Eighteen of 31
eyes (58.06%) also exhibited "inverted inflow phenomena." In Group Two, both the
SFCT and CA of eyes with diabetic macular edema and serous macular detachment
were significantly greater than those in the other eyes. The CA in panretinal
photocoagulation (PRP) treated cases was also greater than that in non-PRP
treated cases. CONCLUSIONS: Early hypofluorescent spots, late choroidal non
perfusion regions, inverted inflow phenomena, higher SFCT, and larger CA are
qualitative and quantitative indexes for DC. Moreover, the late choroidal non
perfusion region is a risk factor for DC with DR. Our study suggests that the
supplemental use of ICGA and EDI SD-OCT with FFA is a better choice for DR
patients.
PMID- 24349523
TI - Widespread misinterpretable ChIP-seq bias in yeast.
AB - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is widely used to
detect genome-wide interactions between a protein of interest and DNA in vivo.
Loci showing strong enrichment over adjacent background regions are typically
considered to be sites of binding. Insufficient attention has been given to
systematic artifacts inherent to the ChIP-seq procedure that might generate a
misleading picture of protein binding to certain loci. We show here that
unrelated transcription factors appear to consistently bind to the gene bodies of
highly transcribed genes in yeast. Strikingly, several types of negative control
experiments, including a protein that is not expected to bind chromatin, also
showed similar patterns of strong binding within gene bodies. These false
positive signals were evident across sequencing platforms and immunoprecipitation
protocols, as well as in previously published datasets from other labs. We show
that these false positive signals derive from high rates of transcription, and
are inherent to the ChIP procedure, although they are exacerbated by sequencing
library construction procedures. This expression bias is strong enough that a
known transcriptional repressor like Tup1 can erroneously appear to be an
activator. Another type of background bias stems from the inherent nucleosomal
structure of chromatin, and can potentially make it seem like certain factors
bind nucleosomes even when they don't. Our analysis suggests that a mock ChIP
sample offers a better normalization control for the expression bias, whereas the
ChIP input is more appropriate for the nucleosomal periodicity bias. While these
controls alleviate the effect of the biases to some extent, they are unable to
eliminate it completely. Caution is therefore warranted regarding the
interpretation of data that seemingly show the association of various
transcription and chromatin factors with highly transcribed genes in yeast.
PMID- 24349524
TI - Inhibition of PI3K/mTOR overcomes nilotinib resistance in BCR-ABL1 positive
leukemia cells through translational down-regulation of MDM2.
AB - Chronic myeloid leukemia (CML) is a cytogenetic disorder resulting from formation
of the Philadelphia chromosome (Ph), that is, the t(9;22) chromosomal
translocation and the formation of the BCR-ABL1 fusion protein. Tyrosine kinase
inhibitors (TKI), such as imatinib and nilotinib, have emerged as leading
compounds with which to treat CML. t(9;22) is not restricted to CML, 20-30% of
acute lymphoblastic leukemia (ALL) cases also carry the Ph. However, TKIs are not
as effective in the treatment of Ph+ ALL as in CML. In this study, the Ph+ cell
lines JURL-MK2 and SUP-B15 were used to investigate TKI resistance mechanisms and
the sensitization of Ph+ tumor cells to TKI treatment. The annexin V/PI
(propidium iodide) assay revealed that nilotinib induced apoptosis in JURL-MK2
cells, but not in SUP-B15 cells. Since there was no mutation in the tyrosine
kinase domain of BCR-ABL1 in cell line SUP-B15, the cells were not generally
unresponsive to TKI, as evidenced by dephosphorylation of the BCR-ABL1 downstream
targets, Crk-like protein (CrkL) and Grb-associated binder-2 (GAB2). Resistance
to apoptosis after nilotinib treatment was accompanied by the constitutive and
nilotinib unresponsive activation of the phosphoinositide 3-kinase (PI3K)
pathway. Treatment of SUP-B15 cells with the dual PI3K/mammalian target of
rapamycin (mTOR) inhibitor BEZ235 alone induced apoptosis in a low percentage of
cells, while combining nilotinib and BEZ235 led to a synergistic effect. The main
role of PI3K/mTOR inhibitor BEZ235 and the reason for apoptosis in the nilotinib
resistant cells was the block of the translational machinery, leading to the
rapid downregulation of the anti-apoptotic protein MDM2 (human homolog of the
murine double minute-2). These findings highlight MDM2 as a potential therapeutic
target to increase TKI-mediated apoptosis and imply that the combination of
PI3K/mTOR inhibitor and TKI might form a novel strategy to combat TKI-resistant
BCR-ABL1 positive leukemia.
PMID- 24349525
TI - Effects of resveratrol on the recovery of muscle mass following disuse in the
plantaris muscle of aged rats.
AB - Aging is associated with poor skeletal muscle regenerative ability following
extended periods of hospitalization and other forms of muscular disuse.
Resveratrol (3,5,4'-trihydroxystilbene) is a natural phytoalexin which has been
shown in skeletal muscle to improve oxidative stress levels in muscles of aged
rats. As muscle disuse and reloading after disuse increases oxidative stress, we
hypothesized that resveratrol supplementation would improve muscle regeneration
after disuse. A total of thirty-six male Fisher 344 * Brown Norway rats (32 mo.)
were treated with either a water vehicle or resveratrol via oral gavage. The
animals received hindlimb suspension for 14 days. Thereafter, they were either
sacrificed or allowed an additional 14 day period of cage ambulation during
reloading. A total of six rats from the vehicle and the resveratrol treated
groups were used for the hindlimb suspension and recovery protocols. Furthermore,
two groups of 6 vehicle treated animals maintained normal ambulation throughout
the experiment, and were used as control animals for the hindlimb suspension and
reloading groups. The data show that resveratrol supplementation was unable to
attenuate the decreases in plantaris muscle wet weight during hindlimb suspension
but it improved muscle mass during reloading after hindlimb suspension. Although
resveratrol did not prevent fiber atrophy during the period of disuse, it
increased the fiber cross sectional area of type IIA and IIB fibers in response
to reloading after hindlimb suspension. There was a modest enhancement of
myogenic precursor cell proliferation in resveratrol-treated muscles after
reloading, but this failed to reach statistical significance. The resveratrol
associated improvement in type II fiber size and muscle mass recovery after
disuse may have been due to decreases in the abundance of pro-apoptotic proteins
Bax, cleaved caspase 3 and cleaved caspase 9 in reloaded muscles. Resveratrol
appears to have modest therapeutic benefits for improving muscle mass after
disuse in aging.
PMID- 24349527
TI - Calling by domestic piglets during simulated crushing and isolation: a signal of
need?
AB - This study examined whether piglet distress vocalizations vary with age, body
weight and health status, according to the predictions of the honest signalling
of need evolutionary model. Vocalizations were recorded during manual squeezing
(a simulation of being crushed by mother sow) and during isolation on Days 1 and
7 after birth in piglets from 15 litters. We predicted that during squeezing,
younger, lighter and sick piglets would call more intensely because they are in
higher risk of dying during crushing and therefore they benefit more from the
sow's reaction to intensive vocalization. For isolation, we predicted that
lighter and younger piglets would call more because they are more vulnerable to
adverse effects of the separation. Calls were analyzed in their time and
frequency domain. The rate of calling, call duration, proportion of high-pitched
calls and eight acoustic parameters characterizing frequency distribution and
tonality were used as indicators of acoustic signalling intensity. Piglets that
experienced "squeezing" on Day 1 produced more intense acoustic distress
signalling than on Day 7. Lighter piglets called more during squeezing than
heavier piglets. Health status did not significantly affect any of the indicators
of intensity of vocalization during squeezing. In isolation, none of the
parameters of vocalization intensity were affected either by the age or by the
weight of the piglets. In summary, the model of honest signalling of need was
confirmed in the squeezed situation, but not in the isolation situation.
PMID- 24349526
TI - APEX nuclease (multifunctional DNA repair enzyme) 1 gene Asp148Glu polymorphism
and cancer risk: a meta-analysis involving 58 articles and 48903 participants.
AB - BACKGROUND: Polymorphisms in the APEX nuclease (multifunctional DNA repair
enzyme) 1 gene (APEX1) may be involved in the carcinogenesis by affecting DNA
repair. We aimed to summarize available data on the association of the APEX1
Asp148Glu (rs1130409) polymorphism with risk of multiple types of cancer via a
meta-analysis. METHODS AND RESULTS: In total, 58 qualified articles including
22,398 cancer patients and 26,505 controls were analyzed, and the data were
extracted independently by two investigators. Analyses of the full data set
indicated a marginally significant association of the APEX1 Asp148Glu
polymorphism with cancer risk under allelic (odds ratio (OR)=1.05; 95% confidence
interval (95% CI): 0.99-1.11; P=0.071), dominant (OR=1.09; 95% CI: 1.01-1.17;
P=0.028), and heterozygous genotypic (OR=1.08; 95% CI: 1.01-1.16; P=0.026)
models, with significant heterogeneity and publication bias. In subgroup analyses
by cancer type, with a Bonferroni corrected alpha of 0.05/6, significant
association was observed for gastric cancer under both dominant (OR=1.74; 95% CI:
1.2-2.51; P=0.003) and heterozygous genotypic (OR=1.66; 95% CI: 1.2-2.31;
P=0.002) models. In subgroup analysis by ethnicity, risk estimates were augmented
in Caucasians, especially under dominant (OR=1.11; 95% CI: 1.0-1.24; P=0.049) and
heterozygous genotypic (OR=1.11; 95% CI: 0.99-1.24; P=0.063) models. By study
design, there were no significant differences between population-based and
hospital-based studies. In subgroup analysis by sample size, risk estimates were
remarkably overestimated in small studies, and no significance was reached in
large studies except under the heterozygous genotypic model (OR=1.23; 95% CI:
1.06-1.43; P=0.006, significant at a Bonferroni corrected alpha of 0.05/2). By
quality score, the risk estimates, albeit nonsignificant, were higher in low
quality studies than in high-quality studies. Further meta-regression analyses
failed to identify any contributory confounders for the associated risk
estimates. CONCLUSIONS: Our findings suggest that APEX1 Asp148Glu polymorphism
might be a genetic risk factor for the development of gastric cancer. Further
investigations on large populations are warranted.
PMID- 24349528
TI - Evaluation of assembly strategies using RNA-seq data associated with grain
development of wheat (Triticum aestivum L.).
AB - Wheat (Triticum aestivum L.) is one of the most important crops cultivated
worldwide. Identifying the complete transcriptome of wheat grain could serve as
foundation for further study of wheat seed development. However, the relatively
large size and the polyploid complexity of the genome have been substantial
barriers to molecular genetics and transcriptome analysis of wheat.
Alternatively, RNA sequencing has provided some useful information about wheat
genes. However, because of the large number of short reads generated by RNA
sequencing, factors that are crucial to transcriptome assembly, including
software, candidate parameters and assembly strategies, need to be optimized and
evaluated for wheat data. In the present study, four cDNA libraries associated
with wheat grain development were constructed and sequenced. A total of 14.17 Gb
of high-quality reads were obtained and used to assess different assembly
strategies. The most successful approach was to filter the reads with Q30 prior
to de novo assembly using Trinity, merge the assembled contigs with genes
available in wheat cDNA reference data sets, and combine the resulting assembly
with an assembly from a reference-based strategy. Using this approach, a
relatively accurate and nearly complete transcriptome associated with wheat grain
development was obtained, suggesting that this is an effective strategy for
generation of a high-quality transcriptome from RNA sequencing data.
PMID- 24349529
TI - Global transcriptome sequencing using the Illumina platform and the development
of EST-SSR markers in autotetraploid alfalfa.
AB - BACKGROUND: Alfalfa is the most widely cultivated forage legume and one of the
most economically valuable crops in the world. The large size and complexity of
the alfalfa genome has delayed the development of genomic resources for alfalfa
research. Second-generation Illumina transcriptome sequencing is an efficient
method for generating a global transcriptome sequence dataset for gene discovery
and molecular marker development in alfalfa. METHODOLOGY/PRINCIPAL FINDINGS: More
than 28 million sequencing reads (5.64 Gb of clean nucleotides) were generated by
Illumina paired-end sequencing from 15 different alfalfa tissue samples. In
total, 40,433 unigenes with an average length of 803 bp were obtained by de novo
assembly. Based on a sequence similarity search of known proteins, a total of
36,684 (90.73%) unigenes were annotated. In addition, 1,649 potential EST-SSRs
were identified as potential molecular markers from unigenes with lengths
exceeding 1 kb. A total of 100 pairs of PCR primers were randomly selected to
validate the assembly quality and develop EST-SSR markers from genomic DNA. Of
these primer pairs, 82 were able to amplify sequences in initial screening tests,
and 27 primer pairs successfully amplified DNA fragments and detected significant
amounts of polymorphism among 10 alfalfa accessions. CONCLUSIONS/SIGNIFICANCE:
The present study provided global sequence data for autotetraploid alfalfa and
demonstrates the Illumina platform is a fast and effective approach to EST-SSR
markers development in alfalfa. The use of these transcriptome datasets will
serve as a valuable public information platform to accelerate studies of the
alfalfa genome.
PMID- 24349531
TI - Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri
region with complete mtDNA genome sequences and Y-chromosomal markers.
AB - Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are
spread over a wide area of northern Asia, whereas their linguistic relatives the
Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the
lower Amur River. The prehistory and relationships of these Tungusic peoples are
as yet poorly investigated, especially with respect to their interactions with
neighbouring populations. In this study, we analyse over 500 complete mtDNA
genome sequences from nine different Evenk and even subgroups as well as their
geographic neighbours from Siberia and their linguistic relatives the Udegey from
the Amur-Ussuri region in order to investigate the prehistory of the Tungusic
populations. These data are supplemented with analyses of Y-chromosomal
haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian
populations. We demonstrate that whereas the North Tungusic Evenks and Evens show
evidence of shared ancestry both in the maternal and in the paternal line, this
signal has been attenuated by genetic drift and differential gene flow with
neighbouring populations, with isolation by distance further shaping the maternal
genepool of the Evens. The Udegey, in contrast, appear quite divergent from their
linguistic relatives in the maternal line, with a mtDNA haplogroup composition
characteristic of populations of the Amur-Ussuri region. Nevertheless, they show
affinities with the Evenks, indicating that they might be the result of admixture
between local Amur-Ussuri populations and Tungusic populations from the north.
PMID- 24349530
TI - Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive
effectors in synoviocytes.
AB - INTRODUCTION: Rheumatoid arthritis (RA) is an inflammatory disease of the joint
characterized by chronic synovitis causing pain, swelling and loss of function
due to destruction of cartilage and bone. The complex series of pathological
events occurring in RA is largely regulated via excessive production of pro
inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The
objective of this work was to elucidate possible involvement of group IVA
cytosolic phospholipase A2 (cPLA2alpha) in TNF-induced regulation of synovitis
and joint destructive effectors in RA, to evaluate the potential of cPLA2alpha as
a future therapeutic target. METHODS: The involvement of cPLA2alpha in tumor
necrosis factor (TNF)-induced intracellular signaling cascades in synoviocytes
(synovial fibroblast-like cells) was analyzed by arachidonic acid (AA) release
assay, synoviocyte enzyme activity assay, gene expression analysis by real-time
PCR and ELISA immunoassay for the detection of prostaglandin E2 (PGE2),
interleukin 8 (IL8) and stromelysin-1 (MMP3), respectively. RESULTS: Inhibitors
of cPLA2alpha enzyme activity (AVX002, ATK) significantly reduced TNF-induced
cellular release of AA, PGE2, IL8 and MMP3. This reduction was evident both at
transcriptional, protein or metabolite levels. Interestingly, cPLA2alpha
inhibition affected several key points of the arachidonyl cascade; AA-release,
cyclooxygenase-2 (COX2) expression and PGE2 production. Furthermore, the results
suggest that cPLA2alpha is subject to transcriptional auto-regulation as
inhibition of cPLA2alpha resulted in reduced PLA2G4A gene expression in TNF
stimulated synoviocytes. CONCLUSIONS: cPLA2alpha appears to be an important
regulator of central effectors of inflammation and joint destruction, namely
MMP3, IL8, COX2, and PGE2. Decreased transcription of the PLA2G4A and COX2 genes
in response to cPLA2alpha enzyme inhibition further suggest a self-reinforcing
effect of cPLA2alpha inhibition in response to TNF. Collectively, these results
support that cPLA2alpha is an attractive therapeutic target candidate as its
inhibition reduces the production of multiple key pro-inflammatory factors
involved in RA pathogenesis.
PMID- 24349532
TI - Impact of interleukin-18 polymorphisms -607A/C and -137G/C on oral cancer
occurrence and clinical progression.
AB - BACKGROUND: The purpose of this study was to identify gene polymorphisms of
interleukin-18 (IL-18) -607A/C and -137G/C specific to patients with oral cancer
susceptibility and clinicopathological status. METHODOLOGY AND PRINCIPAL
FINDINGS: A total of 1,126 participants, including 559 healthy people and 567
patients with oral cancer, were recruited for this study. Allelic discrimination
of -607A/C (rs1946518) and -137G/C (rs187238) polymorphisms of the IL-18 gene was
assessed by a real-time PCR with the TaqMan assay. There was no significant
association between IL-18 -607A/C polymorphism and oral cancer risk. However,
among alcohol consumers, people with A/A homozygotes of IL-18 -607A/C
polymorphism had a 2.38-fold (95% CI=1.17-4.86; p=0.01) increased risk of
developing oral cancer compared with those with C/C homozygotes. The participants
with G/C heterozygotes of IL-18 -137 polymorphism had a 1.64-fold (95% CI: 1.08
2.48; p=0.02) increased risk of developing oral cancer compared with those with
G/G wild type homozygotes. Both sets of statistics were determined after
adjusting for confounding factors. Among people who had exposure to oral cancer
related environmental risk factors such as areca, alcohol, and tobacco
consumption, the adjusted odd ratios and 95% confidence intervals were increased
to a 2.02-fold (95% CI=1.01-4.04; p=0.04), 4.04 (95% CI=1.65-9.87; p=0.002) and a
1.66-fold (95% CI=1.00-2.84; p=0.05) risk of developing oral cancer. However,
patients with G/C alleles of IL-18 -137 were correlated with a lower clinical
stage (AOR=0.59; 95% CI=0.39-0.89; p=0.01), smaller tumor size (AOR=0.56; 95%
CI=0.35-0.87; p=0.01), and non-lymph node metastasis (AOR=0.51; 95% CI=0.32-0.80;
p=0.003). CONCLUSION: IL-18 -137 G/C gene polymorphism may be a factor that
increases the susceptibility to oral cancer, as well as a protective factor for
oral cancer progression. The interactions of gene to oral cancer-related
environmental risk factors have a synergetic effect that can further enhance oral
cancer development.
PMID- 24349533
TI - Periostin responds to mechanical stress and tension by activating the MTOR
signaling pathway.
AB - Current knowledge about Periostin biology has expanded from its recognized
functions in embryogenesis and bone metabolism to its roles in tissue repair and
remodeling and its clinical implications in cancer. Emerging evidence suggests
that Periostin plays a critical role in the mechanism of wound healing; however,
the paracrine effect of Periostin in epithelial cell biology is still poorly
understood. We found that epithelial cells are capable of producing endogenous
Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells
responded to Periostin paracrine stimuli by enhancing cellular migration and
proliferation and by activating the mTOR signaling pathway. Interestingly,
biomechanical stimulation of epithelial cells, which simulates tension forces
that occur during initial steps of tissue healing, induced Periostin production
and mTOR activation. The molecular association of Periostin and mTOR signaling
was further dissected by administering rapamycin, a selective pharmacological
inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins
implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both
strategies resulted in ablation of Periostin-induced mitogenic and migratory
activity. These results indicate that Periostin-induced epithelial migration and
proliferation requires mTOR signaling. Collectively, our findings identify
Periostin as a mechanical stress responsive molecule that is primarily secreted
by fibroblasts during wound healing and expressed endogenously in epithelial
cells resulting in the control of cellular physiology through a mechanism
mediated by the mTOR signaling cascade.
PMID- 24349534
TI - Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced
vascular calcification.
AB - The transdifferentiation of vascular smooth muscle cells (VSMCs) into osteoblast
like cells has been implicated in the context of vascular calcification. We
investigated the roles of vitamin D receptor (Vdr) and runt-related transcription
factor 2 (Runx2) in the osteoblastic differentiation of VSMCs in response to
vitamin D3 using in vitro VSMCs cultures and in vivo in Vdr knockout (Vdr(-/-))
and Runx2 carboxy-terminus truncated heterozygous (Runx2(+/DeltaC)) mice.
Treatment of VSMCs with active vitamin D3 promoted matrix mineral deposition, and
increased the expressions of Vdr, Runx2, and of osteoblastic genes but decreased
the expression of smooth muscle myosin heavy chain in primary VSMCs cultures.
Immunoprecipitation experiments suggested an interaction between Vdr and Runx2.
Furthermore, silencing Vdr or Runx2 attenuated the procalcific effects of vitamin
D3. Functional cooperation between Vdr and Runx2 in vascular calcification was
also confirmed in in vivo mouse models. Vascular calcification induced by high
dose vitamin D3 was completely inhibited in Vdr(-/-) or Runx2(+/DeltaC) mice,
despite elevated levels of serum calcium or alkaline phosphatase. Collectively,
these findings suggest that functional cooperation between Vdr and Runx2 is
necessary for vascular calcification in response to vitamin D3.
PMID- 24349535
TI - Improved mitochondrial function underlies the protective effect of pirfenidone
against tubulointerstitial fibrosis in 5/6 nephrectomized rats.
AB - Dysfunctional mitochondria participate in the progression of chronic kidney
disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its
mechanism remains unclear. Mitochondrial dysfunction is an early event that
occurs prior to the onset of renal fibrosis. In this context, we investigated the
protective effect of pirfenidone on mitochondria and its relevance to apoptosis
and oxidative stress in renal proximal tubular cells. A remnant kidney rat model
was established. Human renal proximal tubular epithelial cells (HK2) using
rotenone, a mitochondrial respiratory chain complex Iota inhibitor were further
investigated in vitro to examine the mitochondrial protective effect of
pirfenidone. Pirfenidone protected mitochondrial structures and functions by
stabilizing the mitochondrial membrane potential, maintaining ATP production and
improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased
tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling
pathway. Pirfenidone also reduced oxidative stress by enhancing manganese
superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen
species (ROS) generation, which suggested that the anti-oxidant effects occurred
at least partially via the mitochondrial pathway. Pirfenidone may be effective
prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic
effect by protection of mitochondria in renal proximal tubular cells.
PMID- 24349536
TI - Efficacy and tolerability of the fixed combinations latanoprost/timolol versus
dorzolamide/timolol in patients with elevated intraocular pressure: a meta
analysis of randomized controlled trials.
AB - OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination of
Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with
elevated intraocular pressure (IOP). METHODS: A comprehensive literature meta
analysis was performed according to the Cochrane Collaboration methodology to
identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with
dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates
were measured by the weight mean difference (WMD) for the IOP reduction (IOPR)
from baseline to end point, including the diurnal mean IOPR, 8 AM IOPR, 12 PM
IOPR, and 4 PM IOPR. The tolerability estimates were measured by RR for adverse
events. All outcomes were reported with a 95% confidence interval (CI). The data
were synthesized by Stata 12.0 SE for Windows. RESULTS: Eight studies involving
841 patients (841 eyes) were included in the meta-analysis. With a WMD of IOPR in
the diurnal mean of 0.16 mmHg (95% CI, -0.31 to 0.63), the FCLT was as effective
as FCDT in lowering IOP in patients with elevated IOP (P = 0.51). The WMDs of
IOPR were 0.58 mmHg (95% CI: -0.002 to 1.17) at 8 AM, -0.07 mmHg (95% CI: -0.50
to 0.36) at 12 PM, and 0.41 mmHg (95% CI: -0.18 to 1.00) at 4 PM, and there were
no significant difference between FCLT and FCDT. FCLT was associated with a
significantly lower incidence of eye pain, bitter taste, and irritation/stinging
than FCDT, with pooled RRs of 0.34 (95% CI: 0.14 to 0.82), 0.06 (95% CI:0.008 to
0.42), and 0.35 (95% CI: 0.14 to 0.85), respectively. CONCLUSION: FCLT was
associated with equivalent efficacy in IOP lowering comparing with FCDT. However,
FCLT was better tolerated than FCDT.
PMID- 24349537
TI - Integrin alpha6beta4 identifies human distal lung epithelial progenitor cells
with potential as a cell-based therapy for cystic fibrosis lung disease.
AB - To develop stem/progenitor cell-based therapy for cystic fibrosis (CF) lung
disease, it is first necessary to identify markers of human lung epithelial
progenitor/stem cells and to better understand the potential for differentiation
into distinct lineages. Here we investigated integrin alpha6beta4 as an
epithelial progenitor cell marker in the human distal lung. We identified a
subpopulation of alpha6beta4(+) cells that localized in distal small airways and
alveolar walls and were devoid of pro-surfactant protein C expression. The
alpha6beta4(+) epithelial cells demonstrated key properties of stem cells ex vivo
as compared to alpha6beta4(-) epithelial cells, including higher colony forming
efficiency, expression of stem cell-specific transcription factor Nanog, and the
potential to differentiate into multiple distinct lineages including basal and
Clara cells. Co-culture of alpha6beta4(+) epithelial cells with endothelial cells
enhanced proliferation. We identified a subset of adeno-associated virus (AAVs)
serotypes, AAV2 and AAV8, capable of transducing alpha6beta4(+) cells. In
addition, reconstitution of bronchi epithelial cells from CF patients with only
5% normal alpha6beta4(+) epithelial cells significantly rescued defects in Cl(-)
transport. Therefore, targeting the alpha6beta4(+) epithelial population via
either gene delivery or progenitor cell-based reconstitution represents a
potential new strategy to treat CF lung disease.
PMID- 24349538
TI - Cell type-specific subcellular localization of phospho-TBK1 in response to
cytoplasmic viral DNA.
AB - Cytoplasmic viral RNA and DNA are recognized by RIG-I-like receptors and DNA
sensors that include DAI, IFI16, DDX41, and cGAS. The RNA and DNA sensors evoke
innate immune responses through the IPS-1 and STING adaptors. IPS-1 and STING
activate TBK1 kinase. TBK1 is phosphorylated in its activation loop, leading to
IRF3/7 activation and Type I interferon (IFN) production. IPS-1 and STING
localize to the mitochondria and endoplasmic reticulum, respectively, whereas it
is unclear where phosphorylated TBK1 is localized in response to cytoplasmic
viral DNA. Here, we investigated phospho-TBK1 (p-TBK1) subcellular localization
using a p-TBK1-specific antibody. Stimulation with vertebrate DNA by transfection
increased p-TBK1 levels. Interestingly, stimulation-induced p-TBK1 exhibited
mitochondrial localization in HeLa and HepG2 cells and colocalized with
mitochondrial IPS-1 and MFN-1. Hepatitis B virus DNA stimulation or herpes
simplex virus type-1 infection also induced p-TBK1 mitochondrial localization in
HeLa cells, indicating that cytoplasmic viral DNA induces p-TBK1 mitochondrial
localization in HeLa cells. In contrast, p-TBK1 did not show mitochondrial
localization in RAW264.7, L929, or T-23 cells, and most of p-TBK1 colocalized
with STING in response to cytoplasmic DNA in those mammalian cells, indicating
cell type-specific localization of p-TBK1 in response to cytoplasmic viral DNA. A
previous knockout study showed that mouse IPS-1 was dispensable for Type I IFN
production in response to cytoplasmic DNA. However, we found that knockdown of
IPS-1 markedly reduced p-TBK1 levels in HeLa cells. Taken together, our data
elucidated the cell type-specific subcellular localization of p-TBK1 and a cell
type-specific role of IPS-1 in TBK1 activation in response to cytoplasmic viral
DNA.
PMID- 24349539
TI - Inferring emotions from speech prosody: not so easy at age five.
AB - Previous research has suggested that children do not rely on prosody to infer a
speaker's emotional state because of biases toward lexical content or situational
context. We hypothesized that there are actually no such biases and that young
children simply have trouble in using emotional prosody. Sixty children from 5 to
13 years of age had to judge the emotional state of a happy or sad speaker and
then to verbally explain their judgment. Lexical content and situational context
were devoid of emotional valence. Results showed that prosody alone did not
enable the children to infer emotions at age 5, and was still not fully mastered
at age 13. Instead, they relied on contextual information despite the fact that
this cue had no emotional valence. These results support the hypothesis that
prosody is difficult to interpret for young children and that this cue plays only
a subordinate role up until adolescence to infer others' emotions.
PMID- 24349541
TI - A predictive model for knee joint replacement in older women.
AB - Knee replacement (KR) is expensive and invasive. To date no predictive algorithms
have been developed to identify individuals at high risk of surgery. This study
assessed whether patient self-reported risk factors predict 10-year KR in a
population-based study of 1,462 women aged over 70 years recruited for the
Calcium Intake Fracture Outcome Study (CAIFOS). Complete hospital records of
prevalent (1980-1998) and incident (1998-2008) total knee replacement were
available via the Western Australian Data Linkage System. Potential risk factors
were assessed for predicative ability using a modeling approach based on a pre
planned selection of risk factors prior to model evaluation. There were 129
(8.8%) participants that underwent KR over the 10 year period. Baseline factors
including; body mass index, knee pain, previous knee replacement and analgesia
use for joint pain were all associated with increased risk, (P < 0.001). These
factors in addition to age demonstrated good discrimination with a C-statistic of
0.79 +/- 0.02 as well as calibration determined by the Hosmer-Lemeshow Goodness
of-Fit test. For clinical recommendations, three categories of risk for 10-year
knee replacement were selected; low < 5%; moderate 5 to < 10% and high >= 10%
predicted risk. The actual risk of knee replacement was; low 16 / 741 (2.2%);
moderate 32 / 330 (9.7%) and high 81 / 391 (20.7%), P < 0.001. Internal
validation of this 5-variable model on 6-year knee replacements yielded a similar
C-statistic of 0.81 +/- 0.02, comparable to the WOMAC weighted score; C-statistic
0.75 +/- 0.03, P = 0.064. In conclusion 5 easily obtained patient self-reported
risk factors predict 10-year KR risk well in this population. This algorithm
should be considered as the basis for a patient-based risk calculator to assist
in the development of treatment regimens to reduce the necessity for surgery in
high risk groups such as the elderly.
PMID- 24349540
TI - An RNAi-based dimorphic genetic screen identified the double bromodomain protein
BET-1 as a sumo-dependent attenuator of RAS-mediated signalling.
AB - Attenuation of RAS/RAF/MAPK signalling is essential to prevent hyperactivation of
this oncogenic pathway. In C. elegans, the sumoylation pathway and a combination
of histone tail modifications regulate gene expression to attenuate the LET-60
(RAS) signalling pathway. We hypothesised that a number of chromatin regulators
are likely to depend on sumoylation to attenuate the pathway. To reveal these, we
designed an RNAi-based dimorphic genetic screen that selects candidates based on
their ability to act as enhancers of a sumo mutant phenotype, such interactions
would suggest that the candidates may be physically associated with sumoylation.
We found 16 enhancers, one of which BET-1, is a conserved double bromodomain
containing protein. We further characterised BET-1 and showed that it can
physically associate with SMO-1 and UBC-9, and that it can be sumoylated in vitro
within the second bromodomain at lysine 252. Previous work has shown that BET-1
can bind acetyl-lysines on histone tails to influence gene expression. In
conclusion, our screening approach has identified BET-1 as a Sumo-dependent
attenuator of LET-60-mediated signalling and our characterisation suggests that
BET-1 can be sumoylated.
PMID- 24349542
TI - National and local influenza surveillance through Twitter: an analysis of the
2012-2013 influenza epidemic.
AB - Social media have been proposed as a data source for influenza surveillance
because they have the potential to offer real-time access to millions of short,
geographically localized messages containing information regarding personal well
being. However, accuracy of social media surveillance systems declines with media
attention because media attention increases "chatter" - messages that are about
influenza but that do not pertain to an actual infection - masking signs of true
influenza prevalence. This paper summarizes our recently developed influenza
infection detection algorithm that automatically distinguishes relevant tweets
from other chatter, and we describe our current influenza surveillance system
which was actively deployed during the full 2012-2013 influenza season. Our
objective was to analyze the performance of this system during the most recent
2012-2013 influenza season and to analyze the performance at multiple levels of
geographic granularity, unlike past studies that focused on national or regional
surveillance. Our system's influenza prevalence estimates were strongly
correlated with surveillance data from the Centers for Disease Control and
Prevention for the United States (r = 0.93, p < 0.001) as well as surveillance
data from the Department of Health and Mental Hygiene of New York City (r = 0.88,
p < 0.001). Our system detected the weekly change in direction (increasing or
decreasing) of influenza prevalence with 85% accuracy, a nearly twofold increase
over a simpler model, demonstrating the utility of explicitly distinguishing
infection tweets from other chatter.
PMID- 24349543
TI - Behaviorally activated mRNA expression profiles produce signatures of learning
and enhanced inhibition in aged rats with preserved memory.
AB - Aging is often associated with cognitive decline, but many elderly individuals
maintain a high level of function throughout life. Here we studied outbred rats,
which also exhibit individual differences across a spectrum of outcomes that
includes both preserved and impaired spatial memory. Previous work in this model
identified the CA3 subfield of the hippocampus as a region critically affected by
age and integral to differing cognitive outcomes. Earlier microarray profiling
revealed distinct gene expression profiles in the CA3 region, under basal
conditions, for aged rats with intact memory and those with impairment. Because
prominent age-related deficits within the CA3 occur during neural encoding of new
information, here we used microarray analysis to gain a broad perspective of the
aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3
expression profiles differentiated aged rats with intact memory from those with
impaired memory. In the activated profile, we observed substantial numbers of
genes (greater than 1000) exhibiting increased expression in aged unimpaired rats
relative to aged impaired, including many involved in synaptic plasticity and
memory mechanisms. This unimpaired aged profile also overlapped significantly
with a learning induced gene profile previously acquired in young adults.
Alongside the increased transcripts common to both young learning and aged rats
with preserved memory, many transcripts behaviorally-activated in the current
study had previously been identified as repressed in the aged unimpaired
phenotype in basal expression. A further distinct feature of the activated
profile of aged rats with intact memory is the increased expression of an
ensemble of genes involved in inhibitory synapse function, which could control
the phenotype of neural hyperexcitability found in the CA3 region of aged
impaired rats. These data support the conclusion that aged subjects with
preserved memory recruit adaptive mechanisms to retain tight control over
excitability under both basal and activated conditions.
PMID- 24349545
TI - The uremic toxin adsorbent AST-120 abrogates cardiorenal injury following
myocardial infarction.
AB - An accelerated progressive decline in renal function is a frequent accompaniment
of myocardial infarction (MI). Indoxyl sulfate (IS), a uremic toxin that
accumulates from the early stages of chronic kidney disease (CKD), is
contributory to both renal and cardiac fibrosis. IS levels can be reduced by
administration of the oral adsorbent AST-120, which has been shown to ameliorate
pathological renal and cardiac fibrosis in moderate to severe CKD. However, the
cardiorenal effect of AST-120 on less severe renal dysfunction in the post-MI
setting has not previously been well studied. MI-induced Sprague-Dawley rats were
randomized to receive either AST-120 (MI+AST-120) or were untreated (MI+Vehicle)
for 16 weeks. Serum IS levels were measured at baseline, 8 and 16 weeks.
Echocardiography and glomerular filtration rate (GFR) were assessed prior to
sacrifice. Renal and cardiac tissues were assessed for pathological changes using
histological and immunohistochemical methods, Western blot analysis and real-time
PCR. Compared with sham, MI+Vehicle animals had a significant reduction in left
ventricular ejection fraction (by 42%, p<0.001) and fractional shortening (by
52%, p<0.001) as well as lower GFR (p<0.05) and increased serum IS levels
(p<0.05). A significant increase in interstitial fibrosis in the renal cortex was
demonstrated in MI+Vehicle animals (p<0.001). Compared with MI+Vehicle, MI+AST
120 animals had increased GFR (by 13.35%, p<0.05) and reduced serum IS (p<0.001),
renal interstitial fibrosis (p<0.05), and renal KIM-1, collagen-IV and TIMP-1
expression (p<0.05). Cardiac function did not change with AST-120 treatment,
however gene expression of TGF-beta1 and TNF-alpha as well as collagen-I and TIMP
1 protein expression was decreased in the non-infarcted myocardium (p<0.05). In
conclusion, reduction of IS attenuates cardio-renal fibrotic processes in the
post-MI kidney. KIM-1 appears to be a sensitive renal injury biomarker in this
setting and is correlated with serum IS levels.
PMID- 24349544
TI - Isolation and characterisation of a recombinant antibody fragment that binds
NCAM1-expressing intervertebral disc cells.
AB - Degeneration of the intervertebral discs (IVD) is a leading cause of neck and low
back pain. Degeneration begins in the central nucleus pulposus region, leading to
loss of IVD osmotic properties. Regeneration approaches include administration of
matrix-mimicking scaffolds, cells and/or therapeutic factors. Cell-targeting
strategies are likely to improve delivery due to the low cell numbers in the IVD.
Single-chain antibody fragments (scFvs) that bind IVD cells were isolated for
potential delivery of therapeutics to degenerated IVD. The most cell-distal
domain of neural cell adhesion molecule 1 (NCAM1) was cloned and expressed in
Escherichia coli. Phage display technology was used to isolate a human scFv
against the recombinant domain by panning a scFv library on the immobilised
protein. The isolated scFv bound cultured rat astrocytes, as well as bovine
nucleus pulposus and annulus fibrosus cells in immunocytochemical studies. The
scFv also labelled cells in bovine spinal cord and six-month and two-year old
bovine IVD sections by immunohistochemistry. Antibody fragments can provide cell
binding moieties at improved cost, time, yield and functionalisation potential
over whole antibodies. The described scFv has potential application in delivery
of therapeutics to NCAM1-expressing cells in degenerated IVD.
PMID- 24349546
TI - Heart rate variability and blood pressure during dynamic and static exercise at
similar heart rate levels.
AB - Aim was to elucidate autonomic responses to dynamic and static (isometric)
exercise of the lower limbs eliciting the same moderate heart rate (HR) response.
METHOD: 23 males performed two kinds of voluntary exercise in a supine position
at similar heart rates: static exercise (SE) of the lower limbs (static leg
press) and dynamic exercise (DE) of the lower limbs (cycling). Subjective effort,
systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP),
rate pressure product (RPP) and the time between consecutive heart beats (RR
intervals) were measured. Time-domain (SDNN, RMSSD), frequency-domain (power in
the low and high frequency band (LFP, HFP)) and geometric measures (SD1, SD2) as
well as non-linear measures of regularity (approximate entropy (ApEn), sample
entropy (SampEn) and correlation dimension D2) were calculated. RESULTS: Although
HR was similar during both exercise conditions (88+/-10 bpm), subjective effort,
SBP, DBP, MAP and RPP were significantly enhanced during SE. HRV indicators
representing overall variability (SDNN, SD 2) and vagal modulated variability
(RMSSD, HFP, SD 1) were increased. LFP, thought to be modulated by both autonomic
branches, tended to be higher during SE. ApEn and SampEn were decreased whereas
D2 was enhanced during SE. It can be concluded that autonomic control processes
during SE and DE were qualitatively different despite similar heart rate levels.
The differences were reflected by blood pressure and HRV indices. HRV-measures
indicated a stronger vagal cardiac activity during SE, while blood pressure
response indicated a stronger sympathetic efferent activity to the vessels. The
elevated vagal cardiac activity during SE might be a response mechanism,
compensating a possible co-activation of sympathetic cardiac efferents, as HR and
LF/HF was similar and LFP tended to be higher. However, this conclusion must be
drawn cautiously as there is no HRV-marker reflecting "pure" sympathetic cardiac
activity.
PMID- 24349547
TI - Diagnosing developmental dyscalculia on the basis of reliable single case FMRI
methods: promises and limitations.
AB - FMRI-studies are mostly based on a group study approach, either analyzing one
group or comparing multiple groups, or on approaches that correlate brain
activation with clinically relevant criteria or behavioral measures. In this
study we investigate the potential of fMRI-techniques focusing on individual
differences in brain activation within a test-retest reliability context. We
employ a single-case analysis approach, which contrasts dyscalculic children with
a control group of typically developing children. In a second step, a support
vector machine analysis and cluster analysis techniques served to investigate
similarities in multivariate brain activation patterns. Children were confronted
with a non-symbolic number comparison and a non-symbolic exact calculation task
during fMRI acquisition. Conventional second level group comparison analysis only
showed small differences around the angular gyrus bilaterally and the left
parieto-occipital sulcus. Analyses based on single-case statistical procedures
revealed that developmental dyscalculia is characterized by individual
differences predominantly in visual processing areas. Dyscalculic children seemed
to compensate for relative under-activation in the primary visual cortex through
an upregulation in higher visual areas. However, overlap in deviant activation
was low for the dyscalculic children, indicating that developmental dyscalculia
is a disorder characterized by heterogeneous brain activation differences. Using
support vector machine analysis and cluster analysis, we tried to group
dyscalculic and typically developing children according to brain activation.
Fronto-parietal systems seem to qualify for a distinction between the two groups.
However, this was only effective when reliable brain activations of both tasks
were employed simultaneously. Results suggest that deficits in number
representation in the visual-parietal cortex get compensated for through finger
related aspects of number representation in fronto-parietal cortex. We conclude
that dyscalculic children show large individual differences in brain activation
patterns. Nonetheless, the majority of dyscalculic children can be differentiated
from controls employing brain activation patterns when appropriate methods are
used.
PMID- 24349548
TI - A lower level of forced expiratory volume in 1 second is a risk factor for all
cause and cardiovascular mortality in a Japanese population: the Takahata study.
AB - Chronic obstructive pulmonary disease is a known risk factor for cardiovascular
death in Western countries. Because Japan has a low cardiovascular death rate,
the association between a lower level of forced expiratory volume in 1 s (FEV1)
and mortality in Japan's general population is unknown. To clarify this, we
conducted a community-based longitudinal study. This study included 3253
subjects, who received spirometry from 2004 to 2006 in Takahata, with a 7-year
follow-up. The causes of death were assessed on the basis of the death
certificate. In 338 subjects, airflow obstruction was observed by spirometry. A
total of 127 subjects died. Cardiovascular death was the second highest cause of
death in this population. The pulmonary functions of the deceased subjects were
significantly lower than those of the subjects who were alive at the end of
follow-up. The relative risk of death by all causes, respiratory failure, lung
cancer, and cardiovascular disease was significantly increased with airflow
obstruction. The Kaplan-Meier analysis showed that all-cause and cardiovascular
mortality significantly increased with a worsening severity of airflow
obstruction. After adjusting for possible factors that could influence prognosis,
a Cox proportional hazard model analysis revealed that a lower level of FEV1 was
an independent risk factor for all-cause and cardiovascular mortality (per 10%
increase; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.98; and
HR, 0.72; 95% CI, 0.61-0.86, respectively). In conclusion, airflow obstruction is
an independent risk factor for all-cause and cardiovascular death in the Japanese
general population. Spirometry might be a useful test to evaluate the risk of
cardiovascular death and detect the risk of respiratory death by lung cancer or
respiratory failure in healthy Japanese individuals.
PMID- 24349549
TI - Does ploidy level directly control cell size? Counterevidence from Arabidopsis
genetics.
AB - Ploidy level affects cell size in many organisms, and ploidy-dependent cell
enlargement has been used to breed many useful organisms. However, how polyploidy
affects cell size remains unknown. Previous studies have explored changes in
transcriptome data caused by polyploidy, but have not been successful. The most
naive theory explaining ploidy-dependent cell enlargement is that increases in
gene copy number increase the amount of protein, which in turn increases the cell
volume. This hypothesis can be evaluated by examining whether any strains,
mutants, or transgenics show the same cell size before and after a
tetraploidization event. I performed this experiment by tetraploidizing various
mutants and transgenics of Arabidopsis thaliana, which show a wide range in cell
size, and found that the ploidy-dependent increase in cell volume is genetically
regulated. This result is not in agreement with the theory described above.
PMID- 24349550
TI - Skin autofluorescence is associated with the progression of chronic kidney
disease: a prospective observational study.
AB - BACKGROUND: Advanced glycation end product (AGE) accumulation is thought to be a
measure of cumulative metabolic stress that has been reported to independently
predict cardiovascular disease in diabetes and renal failure. The aim of this
study was to evaluate the association between AGE accumulation, measured as skin
autofluorescence, and the progression of renal disease in pre-dialysis patients
with chronic kidney disease (CKD). METHODS: Skin autofluorescence was measured
noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis
patients with CKD. The primary end point was defined as a doubling of serum
creatinine and/or need for dialysis. RESULTS: Thirty-three patients were lost to
follow-up. Forty six patients reached the primary end point during the follow-up
period (Median 39 months). Kaplan-Meier analysis showed a significantly higher
risk of development of the primary end points in patients with skin
autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units,
derived by receiver operator curve analysis. Cox regression analysis revealed
that skin autofluorescence was an independent predictor of the primary end point,
even after adjustment for age, gender, smoking history, diabetes, estimated
glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P =
0.004). CONCLUSIONS: Tissue accumulation of AGEs, measured as skin
autofluorescence, is a strong and independent predictor of progression of CKD.
Skin autofluorescence may be useful for risk stratification in this group of
patients; further studies should clarify whether AGE accumulation could be one of
the therapeutic targets to improve the prognosis of CKD.
PMID- 24349551
TI - The effect of lubricin on the gliding resistance of mouse intrasynovial tendon.
AB - The purpose of this study was to investigate the role of lubricin on the gliding
resistance of intrasynovial tendons by comparing lubricin knockout, heterozygous,
and wild type mice. A total of thirty-six deep digital flexor (DDF) tendons in
the third digits of each hind paw from eighteen adult mice were used, including
six lubricin knockout mice (Prg4 -/-), six heterozygous mice (Prg4 +/-), and six
wild type mice (Prg4 +/+). The tendon gliding resistance was measured using a
custom-made device. Tendon structural changes were evaluated by scanning electron
and light microscopy. The gliding resistance of intrasynovial tendons from
lubricin knockout mice was significantly higher than the gliding resistance of
either wild type or heterozygous mice. The surface of the lubricin knockout
tendons appeared to be rougher, compared to the wild type and heterozygous
tendons. Synovial hyperplasia was found in the lubricin knockout mice. Cartilage
like tissue was found in the tendon and pulley of the lubricin knockout mice. Our
findings confirm the importance of lubricin in intrasynovial tendon lubrication.
This knockout model may be useful in determining the effect of lubricin on tendon
healing and the response to injury.
PMID- 24349552
TI - Vitamin D receptor gene polymorphisms on the risk of tuberculosis, a meta
analysis of 29 case-control studies.
AB - The relationship of four potentially functional polymorphisms of the vitamin D
receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility
were considered. The aim of this meta-analysis was to explore the association
between the four polymorphisms and tuberculosis risk in different ethnic
backgrounds. Eligible case-control studies that were catalogued before April
1(st) 2013 were enrolled, and the heterogeneity between the studies was evaluated
using a chi(2) based Q-test. Fixed and random effect models were built to
evaluate the association of the four polymorphisms with the risk of tuberculosis,
and the association between the four polymorphisms and tuberculosis was expressed
as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine
qualified studies were enrolled for this meta-analysis that included 6179
tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of
the FokI polymorphism was associated with a significantly increased risk of
tuberculosis when compared to the heterozygote and wild type homozygote genotypes
in the Chinese population (ff vs. Ff+FF: OR(recessive) =1.97, 95%CI: 1.32-2.93,
P(bonferroni) =0.0032; heterogeneity test: chi(2)=0.24, P=0.62). For European
subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were
associated with a significantly decreased risk of tuberculosis when compared to
the wild type homozygote (bb+Bb vs. BB: OR(dominant) =0.41, 95%CI, 0.22-0.76,
P(bonferroni) =0.02; heterogeneity test: chi(2)=2.59, P=0.11). Based on the above
results, we conclude that variants of the VDR gene that are homozygous for the
FokI polymorphism might be more susceptible to tuberculosis in Chinese.
Furthermore, larger sample studies are warranted to confirm the protective
effects of BsmI variants on tuberculosis in the Europeans.
PMID- 24349553
TI - Greater ethanol-induced locomotor activation in DBA/2J versus C57BL/6J mice is
not predicted by presynaptic striatal dopamine dynamics.
AB - A large body of research has aimed to determine the neurochemical factors driving
differential sensitivity to ethanol between individuals in an attempt to find
predictors of ethanol abuse vulnerability. Here we find that the locomotor
activating effects of ethanol are markedly greater in DBA/2J compared to C57BL/6J
mice, although it is unclear as to what neurochemical differences between strains
mediate this behavior. Dopamine elevations in the nucleus accumbens and caudate
putamen regulate locomotor behavior for most drugs, including ethanol; thus, we
aimed to determine if differences in these regions predict strain differences in
ethanol-induced locomotor activity. Previous studies suggest that ethanol
interacts with the dopamine transporter, potentially mediating its locomotor
activating effects; however, we found that ethanol had no effects on dopamine
uptake in either strain. Ex vivo voltammetry allows for the determination of
ethanol effects on presynaptic dopamine terminals, independent of drug-induced
changes in firing rates of afferent inputs from either dopamine neurons or other
neurotransmitter systems. However, differences in striatal dopamine dynamics did
not predict the locomotor-activating effects of ethanol, since the inhibitory
effects of ethanol on dopamine release were similar between strains. There were
differences in presynaptic dopamine function between strains, with faster
dopamine clearance in the caudate-putamen of DBA/2J mice; however, it is unclear
how this difference relates to locomotor behavior. Because of the role of the
dopamine system in reinforcement and reward learning, differences in dopamine
signaling between the strains could have implications for addiction-related
behaviors that extend beyond ethanol effects in the striatum.
PMID- 24349554
TI - Rapid diversification of FoxP2 in teleosts through gene duplication in the
teleost-specific whole genome duplication event.
AB - As one of the most conserved genes in vertebrates, FoxP2 is widely involved in a
number of important physiological and developmental processes. We systematically
studied the evolutionary history and functional adaptations of FoxP2 in teleosts.
The duplicated FoxP2 genes (FoxP2a and FoxP2b), which were identified in teleosts
using synteny and paralogon analysis on genome databases of eight organisms, were
probably generated in the teleost-specific whole genome duplication event. A
credible classification with FoxP2, FoxP2a and FoxP2b in phylogenetic
reconstructions confirmed the teleost-specific FoxP2 duplication. The
unavailability of FoxP2b in Danio rerio suggests that the gene was deleted
through nonfunctionalization of the redundant copy after the Otocephala
Euteleostei split. Heterogeneity in evolutionary rates among clusters consisting
of FoxP2 in Sarcopterygii (Cluster 1), FoxP2a in Teleostei (Cluster 2) and FoxP2b
in Teleostei (Cluster 3), particularly between Clusters 2 and 3, reveals
asymmetric functional divergence after the gene duplication. Hierarchical cluster
analyses of hydrophobicity profiles demonstrated significant structural
divergence among the three clusters with verification of subsequent stepwise
discriminant analysis, in which FoxP2 of Leucoraja erinacea and Lepisosteus
oculatus were classified into Cluster 1, whereas FoxP2b of Salmo salar was
grouped into Cluster 2 rather than Cluster 3. The simulated thermodynamic
stability variations of the forkhead box domain (monomer and homodimer) showed
remarkable divergence in FoxP2, FoxP2a and FoxP2b clusters. Relaxed purifying
selection and positive Darwinian selection probably were complementary driving
forces for the accelerated evolution of FoxP2 in ray-finned fishes, especially
for the adaptive evolution of FoxP2a and FoxP2b in teleosts subsequent to the
teleost-specific gene duplication.
PMID- 24349555
TI - Transfer of learning between hemifields in multiple object tracking: memory
reduces constraints of attention.
AB - Many tasks involve tracking multiple moving objects, or stimuli. Some require
that individuals adapt to changing or unfamiliar conditions to be able to track
well. This study explores processes involved in such adaptation through an
investigation of the interaction of attention and memory during tracking.
Previous research has shown that during tracking, attention operates
independently to some degree in the left and right visual hemifields, due to
putative anatomical constraints. It has been suggested that the degree of
independence is related to the relative dominance of processes of attention
versus processes of memory. Here we show that when individuals are trained to
track a unique pattern of movement in one hemifield, that learning can be
transferred to the opposite hemifield, without any evidence of hemifield
independence. However, learning is not influenced by an explicit strategy of
memorisation of brief periods of recognisable movement. The findings lend support
to a role for implicit memory in overcoming putative anatomical constraints on
the dynamic, distributed spatial allocation of attention involved in tracking
multiple objects.
PMID- 24349556
TI - Terminal N-acetylgalactosamine-specific leguminous lectin from Wisteria japonica
as a probe for human lung squamous cell carcinoma.
AB - Millettia japonica was recently reclassified into the genus Wisteria japonica
based on chloroplast and nuclear DNA sequences. Because the seed of Wisteria
floribunda expresses leguminous lectins with unique N-acetylgalactosamine-binding
specificity, we purified lectin from Wisteria japonica seeds using ion exchange
and gel filtration chromatography. Glycan microarray analysis demonstrated that
unlike Wisteria floribunda and Wisteria brachybotrys lectins, which bind to both
terminal N-acetylgalactosamine and galactose residues, Wisteria japonica lectin
(WJA) specifically bound to both alpha- and beta-linked terminal N
acetylgalactosamine, but not galactose residues on oligosaccharides and
glycoproteins. Further, frontal affinity chromatography using more than 100 2
aminopyridine-labeled and p-nitrophenyl-derivatized oligosaccharides demonstrated
that the ligands with the highest affinity for Wisteria japonica lectin were
GalNAcbeta1-3GlcNAc and GalNAcbeta1-4GlcNAc, with K(a) values of 9.5 * 10(4) and
1.4 * 10(5) M(-1), respectively. In addition, when binding was assessed in a
variety of cell lines, Wisteria japonica lectin bound specifically to EBC-1 and
HEK293 cells while other Wisteria lectins bound equally to all of the cell lines
tested. Wisteria japonica lectin binding to EBC-1 and HEK293 cells was
dramatically decreased in the presence of N-acetylgalactosamine, but not
galactose, mannose, or N-acetylglucosamine, and was completely abrogated by beta
hexosaminidase-digestion of these cells. These results clearly demonstrate that
Wisteria japonica lectin binds to terminal N-acetylgalactosamine but not
galactose. In addition, histochemical analysis of human squamous cell carcinoma
tissue sections demonstrated that Wisteria japonica lectin specifically bound to
differentiated cancer tissues but not normal tissue. This novel binding
characteristic of Wisteria japonica lectin has the potential to become a powerful
tool for clinical applications.
PMID- 24349557
TI - The ecological associations of surface-dwelling lizards in Qom Province in the
Northwest of Central Plateau of Iran.
AB - We used pitfall trapping to investigate the effects of elevation, plant density
and soil structure on species diversity and the impact of these habitat factors
on lizard habitat selectivity in the Qom Province in the Central Plateau of Iran.
From a total of 12 1-ha plots, we captured 363 individuals of 15 species of
lizards (six species of Lacertidae, five species of Agamidae, two species of
Gekkonidae, one species of Varanidae and one species of Scincidae). A generalized
linear model (GLM) determined that elevation was the most important factor
impacting species diversity. The highest species diversity was at the
intermediate elevation (1289 m). Abundance of 6 out of 15 species showed strong
relationships with some habitat factors. These relationships were demonstrated by
habitat selectivity index (Ivlev's index). Our result supports other surveys that
showed that elevation plays an important role in determining lizard species
diversity.
PMID- 24349558
TI - The histone deacetylase HDAC4 regulates long-term memory in Drosophila.
AB - A growing body of research indicates that pharmacological inhibition of histone
deacetylases (HDACs) correlates with enhancement of long-term memory and current
research is concentrated on determining the roles that individual HDACs play in
cognitive function. Here, we investigate the role of HDAC4 in long-term memory
formation in Drosophila. We show that overexpression of HDAC4 in the adult
mushroom body, an important structure for memory formation, resulted in a
specific impairment in long-term courtship memory, but had no affect on short
term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM,
suggesting a mode of action independent of catalytic activity. We found that
overexpression of HDAC4 resulted in a redistribution of the transcription factor
MEF2 from a relatively uniform distribution through the nucleus into punctate
nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated
in regulation of long-term memory, these data suggest that the repressive effects
of HDAC4 on long-term memory may be through interaction with MEF2. In the same
genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs
long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of
long-term memory, but also modulates normal memory formation.
PMID- 24349559
TI - CD86 is an activation receptor for NK cell cytotoxicity against tumor cells.
AB - CTLA4Ig has been successfully used in the clinic for suppression of T cell
activation. However, patients treated with CTLA4Ig experienced reduced incidence
of tumors than predicted, but the underlying mechanism remains unknown. In this
paper, we showed that brief administration of CTLA4Ig significantly reduced tumor
metastasis and prolonged the survival of host mice bearing B16 melanoma.
Depletion of NK cells prior to CTLA4Ig administration eliminated the CTLA4Ig
mediated anti-tumor activity. CTLA4Ig enhanced NK cell cytotoxicity to tumor
cells via up-regulation of NK cell effecter molecules CD107a and perforin in
vivo. In addition, we demonstrated that, upon activation, NK cells could
significantly increase the expression of CD86 both in vitro and in vivo, and
ligation of CD86 with CTLA4Ig significantly increased the ability of NK cells to
kill tumor cells. Furthermore, a human NK cell line that expressed high level of
CD86 was directly activated by CTLA4Ig so that killing of tumor targets was
enhanced; this enhanced killing could be inhibited by blocking CD86. Our findings
uncover a novel function of CTLA4Ig in tumor immunity and suggest that CD86 on NK
cells is an activating receptor and closely involved in the CTLA4Ig-mediated anti
tumor response.
PMID- 24349560
TI - Linkage analysis in familial non-Lynch syndrome colorectal cancer families from
Sweden.
AB - Family history is a major risk factor for colorectal cancer and many families
segregate the disease as a seemingly monogenic trait. A minority of familial
colorectal cancer could be explained by known monogenic genes and genetic loci.
Familial polyposis and Lynch syndrome are two syndromes where the predisposing
genes are known but numerous families have been tested without finding the
predisposing gene. We performed a genome wide linkage analysis in 121 colorectal
families with an increased risk of colorectal cancer. The families were
ascertained from the department of clinical genetics at the Karolinska University
Hospital in Stockholm, Sweden and were considered negative for Familial Polyposis
and Lynch syndrome. In total 600 subjects were genotyped using single nucleotide
polymorphism array chips. Parametric- and non-parametric linkage analyses were
computed using MERLIN in all and subsets of families. No statistically
significant result was seen, however, there were suggestive positive HLODs above
two in parametric linkage analysis. This was observed in a recessive model for
high-risk families, at locus 9q31.1 (HLOD=2.2, rs1338121) and for moderate-risk
families, at locus Xp22.33 (LOD=2.2 and HLOD=2.5, rs2306737). Using families with
early-onset, recessive analysis suggested one locus on 4p16.3 (LOD=2.2, rs920683)
and one on 17p13.2 (LOD/HLOD=2.0, rs884250). No NPL score above two was seen for
any of the families. Our linkage study provided additional support for the
previously suggested region on chromosome 9 and suggested additional loci to be
involved in colorectal cancer risk. Sequencing of genes in the regions will be
done in future studies.
PMID- 24349561
TI - p120 catenin is required for the stress response in Drosophila.
AB - p120ctn is a ubiquitously expressed core component of cadherin junctions and
essential for vertebrate development. Surprisingly, Drosophila p120ctn (dp120ctn)
is dispensable for adherens junctions and development, which has discouraged
Drosophila researchers from further pursuing the biological role of dp120ctn.
Here we demonstrate that dp120ctn loss results in increased heat shock
sensitivity and reduced animal lifespan, which are completely rescued by ectopic
expression of a dp120ctn-GFP transgene. Transcriptomic analysis revealed multiple
relish/NF-kappaB target genes differentially expressed upon loss of dp120ctn.
Importantly, this aberrant gene expression was rescued by overexpression of
dp120ctn-GFP or heterozygosity for relish. Our results uncover a novel role for
dp120ctn in the regulation of animal stress response and immune signalling. This
may represent an ancient role of p120ctn and can influence further studies in
Drosophila and mammals.
PMID- 24349562
TI - Can force feedback and science learning enhance the effectiveness of neuro
rehabilitation? An experimental study on using a low-cost 3D joystick and a
virtual visit to a zoo.
AB - In this paper, we demonstrate that healthy adults respond differentially to the
administration of force feedback and the presentation of scientific content in a
virtual environment, where they interact with a low-cost haptic device. Subjects
are tasked with controlling the movement of a cursor on a predefined trajectory
that is superimposed on a map of New York City's Bronx Zoo. The system is
characterized in terms of a suite of objective indices quantifying the subjects'
dexterity in planning and generating the multijoint visuomotor tasks. We find
that force feedback regulates the smoothness, accuracy, and duration of the
subject's movement, whereby converging or diverging force fields influence the
range of variations of the hand speed. Finally, our findings provide preliminary
evidence that using educational content increases subjects' satisfaction.
Improving the level of interest through the inclusion of learning elements can
increase the time spent performing rehabilitation tasks and promote learning in a
new context.
PMID- 24349563
TI - Selection of reliable biomarkers from PCR array analyses using relative distance
computational model: methodology and proof-of-concept study.
AB - It is increasingly evident about the difficulty to monitor chemical exposure
through biomarkers as almost all the biomarkers so far proposed are not specific
for any individual chemical. In this proof-of-concept study, adult male zebrafish
(Danio rerio) were exposed to 5 or 25 ug/L 17beta-estradiol (E2), 100 ug/L
lindane, 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 15 mg/L arsenic for
96 h, and the expression profiles of 59 genes involved in 7 pathways plus 2 well
characterized biomarker genes, vtg1 (vitellogenin1) and cyp1a1 (cytochrome P450
1A1), were examined. Relative distance (RD) computational model was developed to
screen favorable genes and generate appropriate gene sets for the differentiation
of chemicals/concentrations selected. Our results demonstrated that the known
biomarker genes were not always good candidates for the differentiation of pair
of chemicals/concentrations, and other genes had higher potentials in some cases.
Furthermore, the differentiation of 5 chemicals/concentrations examined were
attainable using expression data of various gene sets, and the best combination
was the set consisting of 50 genes; however, as few as two genes (e.g. vtg1 and
hspa5 [heat shock protein 5]) were sufficient to differentiate the five
chemical/concentration groups in the present test. These observations suggest
that multi-parameter arrays should be more reliable for biomonitoring of chemical
exposure than traditional biomarkers, and the RD computational model provides an
effective tool for the selection of parameters and generation of parameter sets.
PMID- 24349564
TI - Early weight development of goats experimentally infected with Mycobacterium
avium subsp. paratuberculosis.
AB - Johne's disease is an infectious chronic inflammatory bowel disease in ruminants.
The key factor for the management of this disease is an early positive diagnosis.
Unfortunately, most diagnostics detect animals with Johne's disease in the
clinical stage with positive serology and/or positive fecal cultures. However,
for effective management of the disease within herds, it is important to detect
infected animals as early as possible. This might only be possible with the help
of parameters not specific for Johne's disease but that give an early indication
for chronic infections such as weight development. Here we report our findings on
the development of total body weight and weight gain during the first six months
of goats experimentally infected to induce Johne's disease. Twenty dairy goat
kids age 2 to 5 days were included in this study. Goats were divided into two
groups: a negative control group and a positive infected group. The weight was
obtained weekly throughout the study. Goats of the positive group were infected
at the age of seven weeks. We detected significant changes in weight gain and
total body weight as early as one week after infection. Differences are
significant throughout the six month time period. Weight as a non-specific
parameter should be used to monitor infection especially in studies on Johne's
disease using the goat model. Our study suggests that goats with Johne's disease
have a reduced weight gain and reduced weight when compared with healthy goats of
the same age.
PMID- 24349565
TI - Histopathological analysis of Salmonella chronic carriage in the mouse
hepatopancreatobiliary system.
AB - Salmonella Typhi asymptomatic chronic carriage represents a challenge for the
diagnosis and prevention of typhoid fever in endemic areas. Such carriers are
thought to be reservoirs for further spread of the disease. Gallbladder carriage
has been demonstrated to be mediated by biofilm formation on gallstones and by
intracellular persistence in the gallbladder epithelium of mice. In addition,
both gallstones and chronic carriage have been associated with chronic
inflammation and the development of gallbladder carcinoma. However, the
pathogenic relationship between typhoid carriage and the development of pre
malignant and/or malignant lesions in the hepatopancreatobiliary system as well
as the host-pathogen interactions occurring during chronic carriage remains
unclear. In this study, we monitored the histopathological features of chronic
carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging
from mild to severe were present in infected mice regardless of the presence of
gallstones. Biliary epithelial hyperplasia was observed more commonly in the
gallbladder of mice with gallstones (uninfected or infected). However, pre
malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and
exocrine pancreas, respectively, were only associated with chronic Salmonella
carriage. This study has implications regarding the role of Salmonella chronic
infection and inflammation in the development of pre-malignant lesions in the
epithelium of the gallbladder and pancreas that could lead to oncogenesis.
PMID- 24349566
TI - Oral leucine supplementation is sensed by the brain but neither reduces food
intake nor induces an anorectic pattern of gene expression in the hypothalamus.
AB - Leucine activates the intracellular mammalian target of the rapamycin (mTOR)
pathway, and hypothalamic mTOR signaling regulates food intake. Although central
infusion of leucine reduces food intake, it is still uncertain whether oral
leucine supplementation is able to affect the hypothalamic circuits that control
energy balance. We observed increased phosphorylation of p70s6k in the mouse
hypothalamus after an acute oral gavage of leucine. We then assessed whether
acute oral gavage of leucine induces the activation of neurons in several
hypothalamic nuclei and in the brainstem. Leucine did not induce the expression
of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive
neurons in the area postrema. In addition, oral gavage of leucine acutely
increased the 24 h food intake of mice. Nonetheless, chronic leucine
supplementation in the drinking water did not change the food intake and the
weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat
diet. We assessed the hypothalamic gene expression and observed that leucine
supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK) that
metabolize branched-chain amino acids. Despite these effects, leucine
supplementation did not induce an anorectic pattern of gene expression in the
hypothalamus. In conclusion, our data show that the brain is able to sense oral
leucine intake. However, the food intake is not modified by chronic oral leucine
supplementation. These results question the possible efficacy of leucine
supplementation as an appetite suppressant to treat obesity.
PMID- 24349567
TI - Metamodels for transdisciplinary analysis of wildlife population dynamics.
AB - Wildlife population models have been criticized for their narrow disciplinary
perspective when analyzing complexity in coupled biological - physical - human
systems. We describe a "metamodel" approach to species risk assessment when
diverse threats act at different spatiotemporal scales, interact in non-linear
ways, and are addressed by distinct disciplines. A metamodel links discrete,
individual models that depict components of a complex system, governing the flow
of information among models and the sequence of simulated events. Each model
simulates processes specific to its disciplinary realm while being informed of
changes in other metamodel components by accessing common descriptors of the
system, populations, and individuals. Interactions among models are revealed as
emergent properties of the system. We introduce a new metamodel platform, both to
further explain key elements of the metamodel approach and as an example that we
hope will facilitate the development of other platforms for implementing
metamodels in population biology, species risk assessments, and conservation
planning. We present two examples - one exploring the interactions of dispersal
in metapopulations and the spread of infectious disease, the other examining
predator-prey dynamics - to illustrate how metamodels can reveal complex
processes and unexpected patterns when population dynamics are linked to
additional extrinsic factors. Metamodels provide a flexible, extensible method
for expanding population viability analyses beyond models of isolated population
demographics into more complete representations of the external and intrinsic
threats that must be understood and managed for species conservation.
PMID- 24349568
TI - Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas
aeruginosa biofilms.
AB - The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung
infection, the key mortality factor for cystic fibrosis (CF) patients, is partly
attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has
previously been found to restore aminoglycoside sensitivity in Escherichia coli
by generating a proton-motive force (PMF), suggesting a potential new strategy to
improve antibiotic therapy and reduce disease progression in CF. Here, we used
the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa
persister cells during biofilm growth. Incubation with mannitol (10-40 mM)
increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of
mannitol to pre-grown biofilms was able to revert the persister phenotype and
improve the efficacy of tobramycin. This effect was blocked by the addition of a
PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol.
Addition of glucose and NaCl at high osmolarity also improved the efficacy of
tobramycin although to a lesser extent compared to mannitol. Therefore, the
primary effect of mannitol in reverting biofilm associated persister cells
appears to be an active, physiological response, associated with a minor
contribution of osmotic stress. Mannitol was tested against clinically relevant
strains, showing that biofilms containing a subpopulation of persister cells are
better killed in the presence of mannitol, but a clinical strain with a high
resistance to tobramycin was not affected by mannitol. Overall, these results
suggest that in addition to improvements in lung function by facilitating mucus
clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and
does so through an active, physiological response.
PMID- 24349569
TI - BOLD Granger causality reflects vascular anatomy.
AB - A number of studies have tried to exploit subtle phase differences in BOLD time
series to resolve the order of sequential activation of brain regions, or more
generally the ability of signal in one region to predict subsequent signal in
another region. More recently, such lag-based measures have been applied to
investigate directed functional connectivity, although this application has been
controversial. We attempted to use large publicly available datasets (FCON 1000,
ADHD 200, Human Connectome Project) to determine whether consistent spatial
patterns of Granger Causality are observed in typical fMRI data. For BOLD
datasets from 1,240 typically developing subjects ages 7-40, we measured Granger
causality between time series for every pair of 7,266 spherical ROIs covering the
gray matter and 264 seed ROIs at hubs of the brain's functional network
architecture. Granger causality estimates were strongly reproducible for
connections in a test and replication sample (n=620 subjects for each group), as
well as in data from a single subject scanned repeatedly, both during resting and
passive video viewing. The same effect was even stronger in high temporal
resolution fMRI data from the Human Connectome Project, and was observed
independently in data collected during performance of 7 task paradigms. The
spatial distribution of Granger causality reflected vascular anatomy with a
progression from Granger causality sources, in Circle of Willis arterial inflow
distributions, to sinks, near large venous vascular structures such as dural
venous sinuses and at the periphery of the brain. Attempts to resolve BOLD phase
differences with Granger causality should consider the possibility of
reproducible vascular confounds, a problem that is independent of the known
regional variability of the hemodynamic response.
PMID- 24349571
TI - A case study in serendipity: environmental researchers use of traditional and
social media for dissemination.
AB - In the face of demands for researchers to engage more actively with a wider range
of publics and to capture different kinds of research impacts and engagements, we
explored the ways a small number of environmental researchers use traditional and
social media to disseminate research. A questionnaire was developed to
investigate the impact of different media as a tool to broker contact between
researchers and a variety of different stakeholders (for example, publics, other
researchers, policymakers, journalists) as well as how researchers perceive that
their use of these media has changed over the past five years. The questionnaire
was sent to 504 researchers whose work had featured in a policy-oriented e-news
service. 149 valid responses were received (29%). Coverage in traditional media
(newspapers, broadcast) not only brokers contact with other journalists, but is a
good source of contact from other researchers (n=47, 62%) and members of the
public (n=36, 26%). Although the use of social media was limited amongst our
sample, it did broker contact with other researchers (n=17, 47%) and the public
(n=10, 28%). Nevertheless, few environmental researchers were actively using
social media to disseminate their research findings, with many continuing to rely
on academic journals and face-to-face communication to reach both academic and
public audiences.
PMID- 24349570
TI - Human breast tumor cells are more resistant to cardiac glycoside toxicity than
non-tumorigenic breast cells.
AB - Cardiotonic steroids (CTS), specific inhibitors of Na,K-ATPase activity, have
been widely used for treating cardiac insufficiency. Recent studies suggest that
low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role
in regulating blood pressure, inducing cellular kinase activity, and promoting
cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can
induce reactive oxygen species, growth arrest, and cell death. CTS are being
considered as potential novel therapies in cancer treatment, as they have been
shown to limit tumor cell growth. However, there is a lack of information on the
relative toxicity of tumor cells and comparable non-tumor cells. We have
investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on
cell growth and survival in cell lines exhibiting the full spectrum of non
cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase
activity equally well in all cell lines tested regardless of metastatic
potential. In contrast, the cellular responses to the drugs are different in non
tumor and tumor cells. Ouabain causes greater inhibition of proliferation and
more extensive apoptosis in non-tumor breast cells compared to malignant or
oncogene-transfected cells. In tumor cells, the effects of ouabain are
accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src
inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that
other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity
in breast tumor cells compared to non-tumor cells indicates that CTS are not good
candidates as cancer therapies.
PMID- 24349573
TI - High-aluminum-affinity silica is a nanoparticle that seeds secondary
aluminosilicate formation.
AB - Despite the importance and abundance of aluminosilicates throughout our natural
surroundings, their formation at neutral pH is, surprisingly, a matter of
considerable debate. From our experiments in dilute aluminum and silica
containing solutions (pH ~ 7) we previously identified a silica polymer with an
extraordinarily high affinity for aluminium ions (high-aluminum-affinity silica
polymer, HSP). Here, further characterization shows that HSP is a colloid of
approximately 2.4 nm in diameter with a mean specific surface area of about 1,000
m(2) g(-1) and it competes effectively with transferrin for Al(III) binding.
Aluminum binding to HSP strongly inhibited its decomposition whilst the reaction
rate constant for the formation of the beta-silicomolybdic acid complex indicated
a diameter between 3.6 and 4.1 nm for these aluminum-containing nanoparticles.
Similarly, high resolution microscopic analysis of the air dried aluminum
containing silica colloid solution revealed 3.9 +/- 1.3 nm sized crystalline Al
rich silica nanoparticles (ASP) with an estimated Al:Si ratio of between 2 and 3
which is close to the range of secondary aluminosilicates such as imogolite. Thus
the high-aluminum-affinity silica polymer is a nanoparticle that seeds early
aluminosilicate formation through highly competitive binding of Al(III) ions. In
niche environments, especially in vivo, this may serve as an alternative
mechanism to polyhydroxy Al(III) species binding monomeric silica to form early
phase, non-toxic aluminosilicates.
PMID- 24349572
TI - Double-strand break repair by interchromosomal recombination: an in vivo repair
mechanism utilized by multiple somatic tissues in mammals.
AB - Homologous recombination (HR) is essential for accurate genome duplication and
maintenance of genome stability. In eukaryotes, chromosomal double strand breaks
(DSBs) are central to HR during specialized developmental programs of meiosis and
antigen receptor gene rearrangements, and form at unusual DNA structures and
stalled replication forks. DSBs also result from exposure to ionizing radiation,
reactive oxygen species, some anti-cancer agents, or inhibitors of topoisomerase
II. Literature predicts that repair of such breaks normally will occur by non
homologous end-joining (in G1), intrachromosomal HR (all phases), or sister
chromatid HR (in S/G(2)). However, no in vivo model is in place to directly
determine the potential for DSB repair in somatic cells of mammals to occur by HR
between repeated sequences on heterologs (i.e., interchromosomal HR). To test
this, we developed a mouse model with three transgenes-two nonfunctional green
fluorescent protein (GFP) transgenes each containing a recognition site for the I
SceI endonuclease, and a tetracycline-inducible I-SceI endonuclease transgene. If
interchromosomal HR can be utilized for DSB repair in somatic cells, then I-SceI
expression and induction of DSBs within the GFP reporters may result in a
functional GFP+ gene. Strikingly, GFP+ recombinant cells were observed in
multiple organs with highest numbers in thymus, kidney, and lung. Additionally,
bone marrow cultures demonstrated interchromosomal HR within multiple
hematopoietic subpopulations including multi-lineage colony forming unit
granulocyte-erythrocyte-monocyte-megakaryocte (CFU-GEMM) colonies. This is a
direct demonstration that somatic cells in vivo search genome-wide for homologous
sequences suitable for DSB repair, and this type of repair can occur within early
developmental populations capable of multi-lineage differentiation.
PMID- 24349574
TI - A new theraphosid spider toxin causes early insect cell death by necrosis when
expressed in vitro during recombinant baculovirus infection.
AB - Baculoviruses are the most studied insect viruses in the world and are used for
biological control of agricultural and forest insect pests. They are also used as
versatile vectors for expression of heterologous proteins. One of the major
problems of their use as biopesticides is their slow speed to kill insects. Thus,
to address this shortcoming, insect-specific neurotoxins from arachnids have been
introduced into the baculovirus genome solely aiming to improve its virulence. In
this work, an insecticide-like toxin gene was obtained from a cDNA derived from
the venom glands of the theraphosid spider Brachypelma albiceps. The mature form
of the peptide toxin (called Ba3) has a high content of basic amino acid
residues, potential for three possible disulfide bonds, and a predicted three
stranded beta-sheetDifferent constructions of the gene were engineered for
recombinant baculovirus Autographa californica multiple nuclepolyhedrovirus
(AcMNPV) expression. Five different forms of Ba3 were assessed; (1) the full
length sequence, (2) the pro-peptide and mature region, (3) only the mature
region, and the mature region fused to an (4) insect or a (5) virus-derived
signal peptide were inserted separately into the genome of the baculovirus. All
the recombinant viruses induced cell death by necrosis earlier in infection
relative to a control virus lacking the toxin gene. However, the recombinant
virus containing the mature portion of the toxin gene induced a faster cell death
than the other recombinants. We found that the toxin construct with the signal
peptide and/or pro-peptide regions delayed the necrosis phenotype. When infected
cells were subjected to ultrastructural analysis, the cells showed loss of plasma
membrane integrity and structural changes in mitochondria before death. Our
results suggest this use of baculovirus is a potential tool to help understand or
to identify the effect of insect-specific toxic peptides when produced during
infection of insect cells.
PMID- 24349575
TI - Effect of metal oxide nanoparticles on microbial community structure and function
in two different soil types.
AB - Increased availability of nanoparticle-based products will, inevitably, expose
the environment to these materials. Engineered nanoparticles (ENPs) may thus find
their way into the soil environment via wastewater, dumpsters and other
anthropogenic sources; metallic oxide nanoparticles comprise one group of ENPs
that could potentially be hazardous for the environment. Because the soil
bacterial community is a major service provider for the ecosystem and humankind,
it is critical to study the effects of ENP exposure on soil bacteria. These
effects were evaluated by measuring bacterial community activity, composition and
size following exposure to copper oxide (CuO) and magnetite (Fe3O4) nanosized
(<50 nm) particles. Two different soil types were examined: a sandy loam (Bet
Dagan) and a sandy clay loam (Yatir), under two ENP concentrations (1%, 0.1%).
Results indicate that the bacterial community in Bet-Dagan soil was more
susceptible to change due to exposure to these ENPs, relative to Yatir soil. More
specifically, CuO had a strong effect on bacterial hydrolytic activity, oxidative
potential, community composition and size in Bet-Dagan soil. Few effects were
noted in the Yatir soil, although 1% CuO exposure did cause a significant
decreased oxidative potential and changes to community composition. Fe3O4 changed
the hydrolytic activity and bacterial community composition in Bet-Dagan soil but
did not affect the Yatir soil bacterial community. Furthermore, in Bet-Dagan
soil, abundance of bacteria annotated to OTUs from the Bacilli class decreased
after addition of 0.1% CuO but increased with 1% CuO, while in Yatir soil their
abundance was reduced with 1% CuO. Other important soil bacterial groups,
including Rhizobiales and Sphingobacteriaceae, were negatively affected by CuO
addition to soil. These results indicate that both ENPs are potentially harmful
to soil environments. Furthermore, it is suggested that the clay fraction and
organic matter in different soils interact with the ENPs and reduce their
toxicity.
PMID- 24349576
TI - The role of historical barriers in the diversification processes in open
vegetation formations during the Miocene/Pliocene using an ancient rodent lineage
as a model.
AB - The Neotropics harbors a high diversity of species and several hypotheses have
been proposed to account for this pattern. However, while species of forested
domains are frequently studied, less is known of species from open vegetation
formations occupying, altogether, a larger area than the Amazon Forest. Here we
evaluate the role of historical barriers and the riverine hypothesis in the
speciation patterns of small mammals by analyzing an ancient rodent lineage
(Thrichomys, Hystricomorpha). Phylogenetic and biogeographic analyses were
carried out with mitochondrial and nuclear DNA markers to analyze the
evolutionary relationships between Thrichomys lineages occurring in dry domains
along both banks of the Rio Sao Francisco. This river is one of the longest of
South America whose course and water flow have been modified by inland tectonic
activities and climate changes. Molecular data showed a higher number of lineages
than previously described. The T. inermis species complex with 2n = 26, FN = 48
was observed in both banks of the river showing a paraphyletic arrangement,
suggesting that river crossing had occurred, from east to west. A similar pattern
was also observed for the T. apereoides complex. Thrichomys speciation occurred
in Late Miocene when the river followed a different course. The current
geographic distribution of Thrichomys species and their phylogenetic
relationships suggested the existence of frequent past connections between both
banks in the middle section of the Rio Sao Francisco. The extensive palaeodune
region found in this area has been identified as a centre of endemism of several
vertebrate species and is likely to be a center of Thrichomys diversification.
PMID- 24349585
TI - Two women presenting worsening cutaneous ulcers during pregnancy: diagnosis,
immune response, and follow-up.
PMID- 24349587
TI - MDGs and NTDs: reshaping the global health agenda.
PMID- 24349586
TI - Laboratory-based prospective surveillance for community outbreaks of Shigella
spp. in Argentina.
AB - BACKGROUND: To implement effective control measures, timely outbreak detection is
essential. Shigella is the most common cause of bacterial diarrhea in Argentina.
Highly resistant clones of Shigella have emerged, and outbreaks have been
recognized in closed settings and in whole communities. We hereby report our
experience with an evolving, integrated, laboratory-based, near real-time
surveillance system operating in six contiguous provinces of Argentina during
April 2009 to March 2012. METHODOLOGY: To detect localized shigellosis outbreaks
timely, we used the prospective space-time permutation scan statistic algorithm
of SaTScan, embedded in WHONET software. Twenty three laboratories sent updated
Shigella data on a weekly basis to the National Reference Laboratory. Cluster
detection analysis was performed at several taxonomic levels: for all Shigella
spp., for serotypes within species and for antimicrobial resistance phenotypes
within species. Shigella isolates associated with statistically significant
signals (clusters in time/space with recurrence interval >=365 days) were
subtyped by pulsed field gel electrophoresis (PFGE) using PulseNet protocols.
PRINCIPAL FINDINGS: In three years of active surveillance, our system detected 32
statistically significant events, 26 of them identified before hospital staff was
aware of any unexpected increase in the number of Shigella isolates. Twenty-six
signals were investigated by PFGE, which confirmed a close relationship among the
isolates for 22 events (84.6%). Seven events were investigated epidemiologically,
which revealed links among the patients. Seventeen events were found at the
resistance profile level. The system detected events of public health importance:
infrequent resistance profiles, long-lasting and/or re-emergent clusters and
events important for their duration or size, which were reported to local public
health authorities. CONCLUSIONS/SIGNIFICANCE: The WHONET-SaTScan system may serve
as a model for surveillance and can be applied to other pathogens, implemented by
other networks, and scaled up to national and international levels for early
detection and control of outbreaks.
PMID- 24349584
TI - Dengue research funded by the European Commission-scientific strategies of three
European dengue research consortia.
PMID- 24349588
TI - Venezuelan equine encephalitis viruses (VEEV) in Argentina: serological evidence
of human infection.
AB - Venezuelan equine encephalitis viruses (VEEV) are responsible for human diseases
in the Americas, producing severe or mild illness with symptoms indistinguishable
from dengue and other arboviral diseases. For this reason, many cases remain
without certain diagnosis. Seroprevalence studies for VEEV subtypes IAB, ID, IF
(Mosso das Pedras virus; MDPV), IV (Pixuna virus; PIXV) and VI (Rio Negro virus;
RNV) were conducted in persons from Northern provinces of Argentina: Salta, Chaco
and Corrientes, using plaque reduction neutralization test (PRNT). RNV was
detected in all studied provinces. Chaco presented the highest prevalence of this
virus (14.1%). Antibodies against VEEV IAB and -for the first time- against MDPV
and PIXV were also detected in Chaco province. In Corrientes, seroprevalence
against RNV was 1.3% in the pediatric population, indicating recent infections.
In Salta, this was the first investigation of VEEV members, and antibodies
against RNV and PIXV were detected. These results provide evidence of circulation
of many VEE viruses in Northern Argentina, showing that surveillance of these
infectious agents should be intensified.
PMID- 24349589
TI - New insights into the molecular epidemiology and population genetics of
Schistosoma mansoni in Ugandan pre-school children and mothers.
AB - Significant numbers of pre-school children are infected with Schistosoma mansoni
in sub-Saharan Africa and are likely to play a role in parasite transmission.
However, they are currently excluded from control programmes. Molecular
phylogenetic studies have provided insights into the evolutionary origins and
transmission dynamics of S. mansoni, but there has been no research into
schistosome molecular epidemiology in pre-school children. Here, we investigated
the genetic diversity and population structure of S. mansoni in pre-school
children and mothers living in lakeshore communities in Uganda and monitored for
changes over time after praziquantel treatment. Parasites were sampled from
children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis
Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up
surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct
sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly
diverse with over 230 unique sequences identified. Parasite populations were
genetically differentiated between lakes and non-synonymous mutations were more
diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations
sampled from children showed a similar genetic diversity to those sampled from
mothers, pointing towards a non-linear relationship between duration of exposure
and accumulation of parasite diversity. The genetic diversity six months after
praziquantel treatment was similar to pre-treatment diversity. Our results
confirm the substantial genetic diversity of S. mansoni in East Africa and
provide significant insights into transmission dynamics within young children and
mothers, important information for schistosomiasis control programmes.
PMID- 24349590
TI - Geographic variation in access to dog-bite care in Pakistan and risk of dog-bite
exposure in Karachi: prospective surveillance using a low-cost mobile phone
system.
AB - BACKGROUND: Dog-bites and rabies are under-reported in developing countries such
as Pakistan and there is a poor understanding of the disease burden. We
prospectively collected data utilizing mobile phones for dog-bite and rabies
surveillance across nine emergency rooms (ER) in Pakistan, recording patient
health-seeking behaviors, access to care and analyzed spatial distribution of
cases from Karachi. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 6212 dog-bite
cases were identified over two years starting in February 2009 with largest
number reported from Karachi (59.7%), followed by Peshawar (13.1%) and Hyderabad
(11.4%). Severity of dog-bites was assessed using the WHO classification. Forty
percent of patients had Category I (least severe) bites, 28.1% had Category II
bites and 31.9% had Category III (most severe bites). Patients visiting a large
public hospital ER in Karachi were least likely to seek immediate healthcare at
non-medical facilities (Odds Ratio = 0.20, 95% CI 0.17-0.23, p-value<0.01), and
had shorter mean travel time to emergency rooms, adjusted for age and gender
(32.78 min, 95% CI 31.82-33.78, p-value<0.01) than patients visiting hospitals in
smaller cities. Spatial analysis of dog-bites in Karachi suggested clustering of
cases (Moran's I = 0.02, p value<0.01), and increased risk of exposure in
particular around Korangi and Malir that are adjacent to the city's largest
abattoir in Landhi. The direct cost of operating the mHealth surveillance system
was USD 7.15 per dog-bite case reported, or approximately USD 44,408 over two
years. CONCLUSIONS: Our findings suggest significant differences in access to
care and health-seeking behaviors in Pakistan following dog-bites. The
distribution of cases in Karachi was suggestive of clustering of cases that could
guide targeted disease-control efforts in the city. Mobile phone technologies for
health (mHealth) allowed for the operation of a national-level disease reporting
and surveillance system at a low cost.
PMID- 24349591
TI - Polyfunctional T cell responses in children in early stages of chronic
Trypanosoma cruzi infection contrast with monofunctional responses of long-term
infected adults.
AB - BACKGROUND: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T
cell compartment, characterized by monofunctional (IFN-gamma-only secreting)
parasite-specific T cells and increased levels of terminally differentiated T
cells. It is possible that persistent infection and/or sustained exposure to
parasites antigens may lead to a progressive loss of function of the immune T
cells. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, the quality and
magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi
infected children and compared with long-term T. cruzi-infected adults with no
evidence of heart failure. The phenotype of CD4(+) T cells was also assessed in
T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN
gamma and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was
prevalent among T. cruzi-infected children. Flow cytometric analysis of co
expression profiles of CD4(+) T cells with the ability to produce IFN-gamma, TNF
alpha, or to express the co-stimulatory molecule CD154 in response to T. cruzi
showed polyfunctional T cell responses in most T. cruzi-infected children.
Monofunctional T cell responses and an absence of CD4(+)TNF-alpha(+)-secreting T
cells were observed in T. cruzi-infected adults. A relatively high degree of
activation and differentiation of CD4(+) T cells was evident in T. cruzi-infected
children. CONCLUSIONS/SIGNIFICANCE: Our observations are compatible with our
initial hypothesis that persistent T. cruzi infection promotes eventual
exhaustion of immune system, which might contribute to disease progression in
long-term infected subjects.
PMID- 24349592
TI - Ecology and geography of transmission of two bat-borne rabies lineages in Chile.
AB - Rabies was known to humans as a disease thousands of years ago. In America,
insectivorous bats are natural reservoirs of rabies virus. The bat species
Tadarida brasiliensis and Lasiurus cinereus, with their respective, host-specific
rabies virus variants AgV4 and AgV6, are the principal rabies reservoirs in
Chile. However, little is known about the roles of bat species in the ecology and
geographic distribution of the virus. This contribution aims to address a series
of questions regarding the ecology of rabies transmission in Chile. Analyzing
records from 1985-2011 at the Instituto de Salud Publica de Chile (ISP) and using
ecological niche modeling, we address these questions to help in understanding
rabies-bat ecological dynamics in South America. We found ecological niche
identity between both hosts and both viral variants, indicating that niches of
all actors in the system are undifferentiated, although the viruses do not
necessarily occupy the full geographic distributions of their hosts. Bat species
and rabies viruses share similar niches, and our models had significant
predictive power even across unsampled regions; results thus suggest that
outbreaks may occur under consistent, stable, and predictable circumstances.
PMID- 24349593
TI - Community acceptance of tsetse control baits: a qualitative study in Arua
District, North West Uganda.
AB - BACKGROUND: There is renewed vigour in efforts to eliminate neglected tropical
diseases including sleeping sickness (human African trypanosomiasis or HAT),
including attempts to develop more cost-effective methods of tsetse control. In
the West Nile region of Uganda, newly designed insecticide-treated targets are
being deployed over an area of ~500 km(2). The operational area covers villages
where tsetse control has not been conducted previously. The effectiveness of the
targets will depend, in part, on their acceptance by the local community.
METHODOLOGY/PRINCIPAL FINDINGS: We assessed knowledge, perceptions and acceptance
of tsetse baits (traps, targets) in villages where they had or had not been used
previously. We conducted sixteen focus group discussions with male and female
participants in eight villages across Arua District. Discussions were audio
recorded, translated and transcribed. We used thematic analysis to compare the
views of both groups and identify salient themes. CONCLUSIONS/SIGNIFICANCE:
Despite the villages being less than 10 km apart, community members perceived
deployed baits very differently. Villagers who had never seen traps before
expressed fear, anxiety and panic when they first encountered them. This was
related to associations with witchcraft and "ghosts from the river" which are
traditionally linked with physical or mental illness, death and misfortune. By
contrast, villagers living in areas where traps had been used previously had
positive attitudes towards them and were fully aware of their purpose and
benefits. The latter group reported that they had similar negative perceptions
when tsetse control interventions first started a decade ago. Our results suggest
that despite their proximity, acceptance of traps varies markedly between
villages and this is related to the duration of experience with tsetse control
programs. The success of community-based interventions against tsetse will
therefore depend on early engagements with communities and carefully designed
sensitization campaigns that reach all communities, especially those living in
areas new to such interventions.
PMID- 24349594
TI - Cutaneous distribution and circadian rhythm of Onchocerca lupi microfilariae in
dogs.
AB - BACKGROUND: Among the arthropod-borne nematodes infesting dogs, Onchocerca lupi
(Spirurida: Onchocercidae) is of increasing zoonotic concern, with new human
cases of infection diagnosed in Turkey, Tunisia, Iran and the USA. Knowledge of
the biology of this nematode is meagre. This study aimed at assessing the
distribution and periodicity of O. lupi microfilariae from different body regions
in naturally infested dogs. METHODOLOGY/PRINCIPAL FINDINGS: Skin samples were
collected from six dogs infested with O. lupi but without apparent clinical
signs. Two skin samples were collected from 18 anatomical regions of dog 1 at
necropsy. In addition, single skin biopsies were performed from the forehead,
inter-scapular and lumbar regions of dogs 2-6, in the morning, afternoon, and at
night. Two aliquots of the sediment of each sample were microscopically observed,
microfilariae counted and morphologically and molecularly identified. Most of the
1,667 microfilariae retrieved from dog 1 were in the right ear (59.6%), nose
(26.5%), left ear (6.7%), forehead (3.0%), and inter-scapular (2.9%) regions. In
dogs 2-6, the overall mean number of microfilariae was larger on the head (n =
122.8), followed by the inter-scapular (n = 119.0) and lumbar (n = 12.8) regions.
The overall mean number of microfilariae was larger in the afternoon (153.4),
followed by night (75.4) and morning (25.8). CONCLUSIONS: Onchocerca lupi
microfilariae were more common in the head (i.e., ears and nose) than in the
remaining part of the dog's body, indicating they tend to aggregate in specific
body regions, which are the best sites to collect skin samples for diagnostic
purposes. The periodicity pattern of microfilariae of O. lupi and their
concentration in specific body regions is most likely a result of the co
evolution with their as-yet-unknown vector. The detection of skin microfilariae
in asymptomatic animals, suggests the potential role of these animals as carriers
and reservoirs of O. lupi.
PMID- 24349595
TI - Impact of six rounds of mass drug administration on Brugian filariasis and soil
transmitted helminth infections in eastern Indonesia.
AB - BACKGROUND: The lymphatic filarial parasite Brugia timori occurs only in eastern
Indonesia where it causes high morbidity. The absence of an animal reservoir, the
inefficient transmission by Anopheles mosquitoes and the high sensitivity to
DEC/albendazole treatment make this species a prime candidate for elimination by
mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the
effect of MDA using DEC and albendazole on B. timori and soil transmitted
helminths (STH) in a cross-sectional study of a sentinel village on Alor Island
annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was
26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34
months after the 6(th) round of MDA, MF and antibody rates were only 0.17% and
6.4%, respectively. The MDA campaign had also a beneficial effect on STH.
Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and
11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the
5(th) round of MDA. Unfortunately, STH rates rebounded 34 months after cessation
of MDA and approached pre-MDA rates. However, the intensity of STH infection in
2009 was still reduced, and no heavy infections were detected.
CONCLUSIONS/SIGNIFICANCE: MDA with DEC/albendazole has had a major impact on B.
timori MF and IgG4 antibody rates, providing a proof of principle that
elimination is feasible. We also documented the value of annual DEC/albendazole
as a mass de-worming intervention and the importance of continuing some form of
STH control after cessation of MDA for filariasis.
PMID- 24349596
TI - Temporal patterns of abundance of Aedes aegypti and Aedes albopictus (Diptera:
Culicidae) and mitochondrial DNA analysis of Ae. albopictus in the Central
African Republic.
AB - The invasive Asian tiger mosquito Aedes albopictus (Diptera: Culicidae) was first
reported in central Africa in 2000, in Cameroon, with the indigenous mosquito
species Ae. aegypti (Diptera: Culicidae). Today, this invasive species is present
in almost all countries of the region, including the Central African Republic
(CAR), where it was first recorded in 2009. As invasive species of mosquitoes can
affect the distribution of native species, resulting in new patterns of vectors
and concomitant risk for disease, we undertook a comparative study early and late
in the wet season in the capital and the main cities of CAR to document
infestation and the ecological preferences of the two species. In addition, we
determined the probable geographical origin of invasive populations of Ae.
albopictus with two mitochondrial DNA genes, COI and ND5. Analysis revealed that
Ae. aegypti was more abundant earlier in the wet season and Ae. albopictus in the
late wet season. Used tyres were the most heavily colonized productive larval
habitats for both species in both seasons. The invasive species Ae. albopictus
predominated over the resident species at all sites in which the two species were
sympatric. Mitochondrial DNA analysis revealed broad low genetic diversity,
confirming recent introduction of Ae. albopictus in CAR. Phylogeographical
analysis based on COI polymorphism indicated that the Ae. albopictus haplotype in
the CAR population segregated into two lineages, suggesting multiple sources of
Ae. albopictus. These data may have important implications for vector control
strategies in central Africa.
PMID- 24349598
TI - Corticosteroids for dengue - why don't they work?
AB - BACKGROUND: Dysregulated immune responses may contribute to the clinical
complications that occur in some patients with dengue. FINDINGS: In Vietnamese
pediatric dengue cases randomized to early prednisolone therapy, 81 gene
transcripts (0.2% of the 47,231 evaluated) were differentially abundant in whole
blood between high-dose (2 mg/kg) prednisolone and placebo-treated patients two
days after commencing therapy. Prominent among the 81 transcripts were those
associated with T and NK cell cytolytic functions. Additionally, prednisolone
therapy was not associated with changes in plasma cytokine levels. CONCLUSION:
The inability of prednisolone treatment to markedly attenuate the host immune
response is instructive for planning future therapeutic strategies for dengue.
PMID- 24349597
TI - Private selective sweeps identified from next-generation pool-sequencing reveal
convergent pathways under selection in two inbred Schistosoma mansoni strains.
AB - BACKGROUND: The trematode flatworms of the genus Schistosoma, the causative
agents of schistosomiasis, are among the most prevalent parasites in humans,
affecting more than 200 million people worldwide. In this study, we focused on
two well-characterized strains of S. mansoni, to explore signatures of selection.
Both strains are highly inbred and exhibit differences in life history traits, in
particular in their compatibility with the intermediate host Biomphalaria
glabrata. METHODOLOGY/PRINCIPAL FINDINGS: We performed high throughput sequencing
of DNA from pools of individuals of each strain using Illumina technology and
identified single nucleotide polymorphisms (SNP) and copy number variations
(CNV). In total, 708,898 SNPs were identified and roughly 2,000 CNVs. The SNPs
revealed low nucleotide diversity (pi = 2 * 10(-4)) within each strain and a high
differentiation level (Fst = 0.73) between them. Based on a recently developed in
silico approach, we further detected 12 and 19 private (i.e. specific non
overlapping) selective sweeps among the 121 and 151 sweeps found in total for
each strain. CONCLUSIONS/SIGNIFICANCE: Functional annotation of transcripts lying
in the private selective sweeps revealed specific selection for functions related
to parasitic interaction (e.g. cell-cell adhesion or redox reactions). Despite
high differentiation between strains, we identified evolutionary convergence of
genes related to proteolysis, known as a key virulence factor and a potential
target of drug and vaccine development. Our data show that pool-sequencing can be
used for the detection of selective sweeps in parasite populations and enables
one to identify biological functions under selection.
PMID- 24349599
TI - Comparative clinical study of different multiplex real time PCR strategies for
the simultaneous differential diagnosis between extrapulmonary tuberculosis and
focal complications of brucellosis.
AB - BACKGROUND: Both brucellosis and tuberculosis are chronic-debilitating systemic
granulomatous diseases with a high incidence in many countries in Africa, Central
and South America, the Middle East and the Indian subcontinent. Certain focal
complications of brucellosis and extrapulmonary tuberculosis are very difficult
to differentiate clinically, biologically and radiologically. As the conventional
microbiological methods for the diagnosis of the two diseases have many
limitations, as well as being time-consuming, multiplex real time PCR (M RT-PCR)
could be a promising and practical approach to hasten the differential diagnosis
and improve prognosis. METHODOLOGY/PRINCIPAL FINDINGS: We designed a SYBR Green
single-tube multiplex real-time PCR protocol targeting bcsp31 and the IS711
sequence detecting all pathogenic species and biovars of Brucella genus, the
IS6110 sequence detecting Mycobacterium genus, and the intergenic region senX3
regX3 specifically detecting Mycobacterium tuberculosis complex. The diagnostic
yield of the M RT-PCR with the three pairs of resultant amplicons was then
analyzed in 91 clinical samples corresponding to 30 patients with focal
complications of brucellosis, 24 patients with extrapulmonary tuberculosis, and
36 patients (Control Group) with different infectious, autoimmune or neoplastic
diseases. Thirty-five patients had vertebral osteomyelitis, 21 subacute or
chronic meningitis or meningoencephalitis, 13 liver or splenic abscess, eight
orchiepididymitis, seven subacute or chronic arthritis, and the remaining seven
samples were from different locations. Of the three pairs of amplicons (senX3
regX3+ bcsp3, senX3-regX3+ IS711 and IS6110+ IS711) only senX3-regX3+ IS711 was
100% specific for both the Brucella genus and M. tuberculosis complex. For all
the clinical samples studied, the overall sensitivity, specificity, and positive
and negative predictive values of the M RT-PCR assay were 89.1%, 100%, 85.7% and
100%, respectively, with an accuracy of 93.4%, (95% CI, 88.3-96.5%).
CONCLUSIONS/SIGNIFICANCE: In this study, a M RT-PCR strategy with species
specific primers based on senX3-regX3+IS711 sequences proved to be a sensitive
and specific test, useful for the highly efficient detection of M. tuberculosis
and Brucella spp in very different clinical samples. It thus represents an
advance in the differential diagnosis between some forms of extrapulmonary
tuberculosis and focal complications of brucellosis.
PMID- 24349601
TI - Genes, Economics, and Happiness.
AB - We explore the influence of genetic variation on subjective well-being by
employing a twin design and genetic association study. In a nationally
representative twin sample, we first show that about 33% of the variation in life
satisfaction is explained by genetic variation. Although previous studies have
shown that baseline happiness is significantly heritable, little research has
considered molecular genetic associations with subjective well-being. We study
the relationship between a functional polymorphism on the serotonin transporter
gene (5-HTTLPR) and life satisfaction. We initially find that individuals with
the longer, transcriptionally more efficient variant of this genotype report
greater life satisfaction (n=2,545, p=0.012). However, our replication attempts
on independent samples produce mixed results indicating that more work needs to
be done to better understand the relationship between this genotype and
subjective well-being. This work has implications for how economists think about
the determinants of utility, and the extent to which exogenous shocks might
affect individual well-being.
PMID- 24349602
TI - Prevention of early-term deliveries: much ado about nothing?
PMID- 24349603
TI - Multicystic dysplastic kidney complicated by pyelonephritis.
AB - PATIENT: Female, 21 FINAL DIAGNOSIS: Multicystic Dysplastic Kidney Disease
complicated by pyelonephritis Symptoms: Left flank pain (CVAT) * dysuria * fever
MEDICATION: Levofloxacin Clinical Procedure: Dimercaptosuccinic acid scan *
voiding cystouretrogram Specialty: Nephrology. OBJECTIVE: Rare disease.
BACKGROUND: Multicystic dysplastic kidney (MCDK) is a renal dysplasia
characterized by the presence of multiple cysts that are non-communicating,
separated by dysplastic parenchyma that consumes the renal cortex resulting in a
nonfunctional kidney. MCDK has an incidence of 1: 4300 of live births and is
usually unilateral, most commonly occurring in the left kidney. Simple MCDK is
defined as unilateral dysplasia with a normal contralateral kidney but with
compensatory hypertrophy of the contralateral kidney, and no associated
genitourinary anomalies. CASE REPORT: A 21 year old Hispanic American female,
presented with intermittent, sharp, severe left flank pain, fever and dysuria for
two days but had gradually worsened within the last 24 hours prior to
presentation. Previous history of multicystic dysplastic kidney, diagnosed four
years ago. No pertinent physical examination findings except left costovertebral
angle tenderness (CVAT). Urinalysis findings were positive for infection and
urine culture grew pan sensitive Escherichia coli. A CT scan of abdominal and
pelvis without contrast revealed a normal right kidney and left kidney had
multiple non-communicating dilated cystic spaces, but no hydronephrosis, left
ureteropelvic junction obstruction and finding were consistent with multicystic
dysplastic kidney and also noted perinephric stranding. CONCLUSIONS: VUR is the
most common renal abnormality in patients with MCDK, occurring in about 25% of
contralateral kidney. Infections involving the MCDK are rare. In fact, cases of
infections such as pyelonephritis or an infected renal cyst of MCDK are almost
non-existent in the current literature. This patient presented with findings
consistent with MCDK complicated by pyelonephritis.
PMID- 24349604
TI - Solitary paraganglioma of the hypoglossal nerve: A case report with magnetic
resonance imaging findings.
AB - PATIENT: Female, 58 FINAL DIAGNOSIS: Solitary paraganglioma of the hypoglossal
nerve Symptoms: Neck pain Medication: - Clinical Procedure: Surgical resection
Specialty: Otolaryngology. OBJECTIVE: Rare disease. BACKGROUND: Paragangliomas
are rare neuroendocrine tumors originating in the neural crest. Only a few cases
of hypoglossal paraganglioma have been reported in the published literature. The
localization of hypoglossal paragangliomas close to the carotid artery precludes
determination of tumor origin preoperatively. CASE REPORT: A 58-year-old female
patient was admitted due to neck pain. During physical examination, a significant
mass could not be palpated in the upper left part of the neck, despite
sensitivity during palpation. Atrophy and left deviation of the left half of the
tongue was observed. MRI of the neck revealed a lesion located superior to the
carotid bifurcation between the left internal carotid artery and external carotid
artery. There was atrophy in the left half of the tongue. The neck mass displaced
the left internal carotid artery anteriorly and medially. The operation was
performed with left lateral cervical access. This lesion, which derived from the
hypoglossal nerve, was excised. Following histopathological evaluation, the
lesion was diagnosed as paraganglioma. CONCLUSIONS: Hypoglossal paraganglioma is
quite rare and there are no established criteria for preoperative diagnosis.
Hypoglossal paraganglioma must be considered to determine treatment options if a
lateral neck mass and ipsilateral tongue atrophy are present at the level of the
12th cranial nerve tract.
PMID- 24349605
TI - Diffuse large B-cell lymphoma: A metabolic disorder?
AB - Patient Male, 81 FINAL DIAGNOSIS: Non-Hodgkin lymphoma Symptoms: General weakness
* hypoglycemia * metabolic acidosis MEDICATION: - Clinical Procedure: -
Specialty: Hematology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND:
B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the
Untied States. Metabolic complications may arise from the disease itself or
through its end organ involvement. CASE REPORT: We describe a case of a diffuse
large B cell lymphoma diagnosed by abdominal computed tomography after it
initially presented as hypoglycemia not correctable by dextrose infusion that
instead resulted in increased anion gap metabolic acidosis with elevated lactate
levels. CONCLUSIONS: The case illustrates how lymphomas can present unusually
with hypoglycemia and lactic acidosis, the latter being an ominous sign that can
occur without liver involvement. In this regard, the case demonstrates the
metabolic sequelae of lymphoma that should raise suspicion for an underlying
process. This has implications for diagnosis, treatment, and patient survival.
Attention should be paid especially in the primary care setting in order to
minimize delays in diagnosis.
PMID- 24349606
TI - Esophageal perforation post pneumatic dilatation for achalasia managed by
esophageal stenting.
AB - PATIENT: Female, 82 FINAL DIAGNOSIS: Achalasia Symptoms: Nocturnal regurgtation *
weight loss MEDICATION: - Clinical Procedure: Esophageal stenting Specialty:
Gastroenterology * Hepatology Objective: Unusual or unexpected effect of
treatment. BACKGROUND: Pneumatic dilatation is one of the most effective methods
for treating achalasia. Esophageal perforation is the most serious complication
after pneumatic dilatation and has been reported to occur in the range of 1 to
4.3%. The appropriate management of esophageal perforation can range from
conservative medical treatment to surgical intervention. CASE REPORT: We report a
case of an 82-year-old male who had an 8 month history of dysphagia for solid and
liquids, a 10 lb weight loss and nocturnal regurgitation. The diagnosis of
achalasia was established by endoscopic; barium and manometric criteria. He
underwent a pneumatic dilation with a 30 mm Rigiflex balloon. A confined or
limited esophageal perforation projecting into the mediastinum and located 1-2 cm
above the diaphragm was confirmed by a gastrografin swallow study performed
immediately after the procedure. There was some accompanying epigastric abdominal
pain. PATIENT was treated later that day by placing a fully covered metallic
esophageal stent in addition to antibiotics, proton pump inhibitor, and fasting.
PATIENT was discharged home 3 days later able to eat liquid-soft foods. Follow up
endoscopy 2 weeks later and a gastrografin swallow showed a completely healed
perforation and the stent was removed. Symptomatically he has done well, with no
dysphagia or heartburn at six and twelve months follow up. CONCLUSIONS: Early
esophageal stenting for esophageal perforation after pneumatic dilation for
achalasia is a treatment option which accelerates healing shortens recovery
period, as well as decreasing hospital stay and costs.
PMID- 24349607
TI - The role of the actin cortex in maintaining cell shape.
AB - Considering that the plasma membrane is host to a variety of mechanical cues in
vivo, and the actin cortex is known to support cell shape, it comes as no
surprise that the paired membrane-cortex plays a major role in cellular responses
to deformation. In a recent study, we applied highly localized forces to HeLa
cells in order to examine the deformation response of the membrane and cortex.
Direct visualization of the deformation in the loading plane allowed for the
characterization of the observed time-dependent strain. Despite large magnitude
and long duration loading regimes, the majority of cells recovered their initial
pre-deformed morphology within ~2 min. Unexpectedly, perturbed regions above
large-volume nuclei were shown to be quite soft and had negligible influence on
morphological recovery. The resistance to deformation and ability to recover was
found to be largely influenced by the actin network, and dependent upon rho
kinase mediated contractility.
PMID- 24349608
TI - Study of possible mechanisms involved in the inhibitory effects of coumarin
derivatives on neutrophil activity.
AB - To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3
(4'-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4'-hydroxyphenyl)
dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular
reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA)
stimulated human neutrophils. We studied also the effects of HHC and HHDC on
possible molecular mechanisms which participate in the activation of NADPH
oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms
(alpha, betaII, and delta), and on phosphorylation of the NADPH oxidase subunit
p40(phox). Without affecting cytotoxicity, both coumarines tested were effective
inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC
markedly diminished oxidant production and also, intracellularly, decreased PKC
activity and partly phosphorylation of PKCalpha, betaII. On the other hand, we
did not observe any effect of coumarin derivatives on phosphorylation of PKC
delta and on phosphorylation of the NADPH oxidase subunit p40(phox), which were
suggested to be involved in the PMA-dependent intracellular activation process.
In agreement with our previous findings, we assume that the different molecular
structures of HHC and HHDC with their different physicochemical and free radical
scavenging characteristics are responsible for their diverse effects on the
parameters tested.
PMID- 24349609
TI - Carbon monoxide attenuates dextran sulfate sodium-induced colitis via inhibition
of GSK-3beta signaling.
AB - Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which
mediates the degradation of heme into CO, iron, and biliverdin. Also, CO
ameliorates the human inflammatory bowel diseases and ulcerative colitis.
However, the mechanism for the effect of CO on the inflammatory bowel disease has
not yet been known. In this study, we showed that CO significantly increases
survival percentage, body weight, colon length as well as histologic parameters
in DSS-treated mice. In addition, CO inhalation significantly decreased DSS
induced pro-inflammatory cytokines by inhibition of GSK-3beta in mice model. To
support the in vivo observation, TNF-alpha, iNOS and IL-10 after CO and LiCl
treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow
derived macrophages (BMMs) from DSS treated mice. In addition, we determined that
CO potentially inhibited GSK-3beta activation and decreased TNF-alpha and iNOS
expression by inhibition of NF-kappaB activation in LPS-stimulated U937 and MLN
cells pretreated with CO. Together, our findings indicate that CO attenuates DSS
induced colitis via inhibition of GSK-3beta signaling in vitro and in vivo.
Importantly, this is the first report that investigated the molecular mechanisms
mediated the novel effects of CO via inhibition GSK-3beta in DSS-induced colitis
model.
PMID- 24349610
TI - Accelerated aging in major depression: the role of nitro-oxidative stress.
AB - Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the
pathogenesis of neurodegenerative disorders, and major depression (MD). The
latter is a very frequent psychiatric illness characterized by accelerated aging,
neurodegeneration, high comorbidity with age-related disorders, and premature
mortality; all of these conditions find an explanation in an altered redox
homeostasis. If aging, neurodegeneration, and major depression share a common
biological base in their pathophysiology, common therapeutic tools could be
investigated for the prevention and treatment of these disorders. As an example,
antidepressants have been demonstrated to present neuroprotective and anti
inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants
that stimulate the antioxidant defense systems and interact with the
monoaminergic system show an antidepressant-like activity. Further research on
this topic could lead, in the near future, to the expansion of the therapeutic
possibilities for the treatment of NOS-related disorders.
PMID- 24349611
TI - Is the oxidative DNA damage level of human lymphocyte correlated with the
antioxidant capacity of serum or the base excision repair activity of lymphocyte?
AB - A random screening of human blood samples from 24 individuals of nonsmoker was
conducted to examine the correlation between the oxidative DNA damage level of
lymphocytes and the antioxidant capacity of serum or the base excision repair
(BER) activity of lymphocytes. The oxidative DNA damage level was measured with
comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated
with a modified comet assay including nuclear extract of lymphocytes for
enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent
antioxidant capacity assay. We found that though the endogenous DNA oxidation
levels varied among the individuals, each individual level appeared to be steady
for at least 1 month. Our results indicate that the oxidative DNA damage level is
insignificantly or weakly correlated with antioxidant capacity or BER activity,
respectively. However, lymphocytes from carriers of Helicobacter pylori (HP) or
Hepatitis B virus (HBV) tend to give higher levels of oxidative DNA damage (P <
0.05). Though sera of this group of individuals show no particular tendency with
reduced antioxidant capacity, the respective BER activities of lymphocytes are
lower in average (P < 0.05). Thus, reduction of repair activity may be associated
with the genotoxic effect of HP or HBV infection.
PMID- 24349612
TI - The influence of long term hydrochlorothiazide administration on the relationship
between renin-angiotensin-aldosterone system activity and plasma glucose in
patients with hypertension.
AB - OBJECTIVE: To observe the relationship between changes in renin-angiotensin
aldosterone system (RAAS) activity and blood plasma glucose after administration
of hydrochlorothiazide (HCTZ) for one year in patients with hypertension.
METHODS: 108 hypertensive patients were given 12.5 mg HCTZ per day for one year.
RAAS activity, plasma glucose levels, and other biochemical parameters, as well
as plasma oxidized low density lipoprotein (oxLDL) levels, were measured and
analyzed at baseline, six weeks, and one year after treatment. RESULTS: After one
year of treatment, the reduction in plasma glucose observed between the elevated
plasma renin activity (PRA) group (-0.26 +/- 0.26 mmol/L) and the nonelevated PRA
group (-1.36 +/- 0.23 mmol/L) was statistically significant (P < 0.05). The
decrease of plasma glucose in the elevated Ang II group (-0.17 +/- 0.18 mmol/L)
compared to the nonelevated Ang II group (-1.07 +/- 0.21 mmol/L) was
statistically significant (P < 0.05). The proportion of patients with elevated
plasma glucose in the elevated Ang II group (40.5%) was significantly higher than
those in the nonelevated Ang II group (16.3%) (P < 0.05). The relative oxLDL
level was not affected by the treatment. CONCLUSIONS: Changes in RAAS activity
were correlated with changes in plasma glucose levels after one year of HCTZ
therapy.
PMID- 24349613
TI - Rosmarinic acid-rich extracts of summer savory (Satureja hortensis L.) protect
Jurkat T cells against oxidative stress.
AB - Summer savory (Satureja hortensis L., Lamiaceae) is used in several regions of
the world as a spice and folk medicine. Anti-inflammatory and cytoprotective
effects of S. hortensis and of its rosmarinic acid-rich phenolic fraction have
been demonstrated in animal trials. However, previous studies of rosmarinic acid
in cell models have yielded controversial results. In this study, we investigated
the effects of summer savory extracts on H2O2-challenged human lymphoblastoid
Jurkat T cells. LC-MS analysis confirmed the presence of rosmarinic acid and
flavonoids such as hesperidin and naringin in the phenolic fraction. Adding 25 or
50 uM of H2O2 to the cell culture caused oxidative stress, manifested as
generation of superoxide and peroxyl radicals, reduced cell viability, G0/G1
arrest, and enhanced apoptosis. This stress was significantly alleviated by the
ethanolic and aqueous extracts of S. hortensis and by the partially purified
rosmarinic acid fraction. The application of an aqueous S. hortensis extract
doubled the activity of catalase and superoxide dismutase in the cells. The
production of IL-2 and IL-10 interleukins was stimulated by H2O2 and was further
enhanced by the addition of the S. hortensis extract or rosmarinic acid fraction.
The H2O2-challenged Jurkat cells may serve as a model for investigating cellular
mechanisms of cytoprotective phytonutrient effects.
PMID- 24349614
TI - Tetrahydroxystilbene glucoside attenuates neuroinflammation through the
inhibition of microglia activation.
AB - Neuroinflammation is closely implicated in the pathogenesis of neurological
diseases. The hallmark of neuroinflammation is the microglia activation. Upon
activation, microglia are capable of producing various proinflammatory factors
and the accumulation of these factors contribute to the neuronal damage.
Therefore, inhibition of microglia-mediated neuroinflammation might hold
potential therapy for neurological disorders. 2,3,5,4'-Tetrahydroxystilbene-2-O
beta-D-glucoside (TSG), an active component extracted from Polygonum multiflorum,
is reported to be beneficial for human health with a great number of
pharmacological properties including antioxidant, free radical-scavenging, anti
inflammation, antilipemia, and cardioprotective effects. Recently, TSG-mediated
neuroprotective effects have been well demonstrated. However, the neuroprotective
actions of TSG on microglia-induced neuroinflammation are not known. In the
present study, microglia BV2 cell lines were applied to investigate the anti
neuroinflammatory effects of TSG. Results showed that TSG reduced LPS-induced
microglia-derived release of proinflammatory factors such as TNFalpha, IL-1beta,
and NO. Moreover, TSG attenuated LPS-induced NADPH oxidase activation and
subsequent reactive oxygen species (ROS) production. Further studies indicated
that TSG inhibited LPS-induced NF-kappaB signaling pathway activation. Together,
TSG exerted neuroprotection against microglia-mediated neuroinflammation,
suggesting that TSG might present a promising benefit for neurological disorders
treatment.
PMID- 24349615
TI - Reversal of myoblast aging by tocotrienol rich fraction posttreatment.
AB - Skeletal muscle satellite cells are heavily involved in the regeneration of
skeletal muscle in response to the aging-related deterioration of the skeletal
muscle mass, strength, and regenerative capacity, termed as sarcopenia. This
study focused on the effect of tocotrienol rich fraction (TRF) on regenerative
capacity of myoblasts in stress-induced premature senescence (SIPS). The
myoblasts was grouped as young control, SIPS-induced, TRF control, TRF
pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological
observation, activity of senescence-associated beta-galactosidase (SA-beta
galactosidase), and cell proliferation were determined. 50 MUg/mL TRF treatment
exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit
large flattened cells and prominent intermediate filaments (senescent-like
morphology). The activity of SA-beta-galactosidase was significantly increased,
but the proliferation capacity was significantly reduced as compared to young
control. The activity of SA-beta-galactosidase was significantly reduced and cell
proliferation was significantly increased in the posttreatment group whereas
there was no significant difference in SA-beta-galactosidase activity and
proliferation capacity of pretreatment group as compared to SIPS-induced
myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts
aging through replenishing the regenerative capacity of the cells. However,
further investigation on the mechanism of TRF in reversing the myoblast aging is
needed.
PMID- 24349616
TI - Protective role of melatonin in neonatal diseases.
AB - Oxidative stress contributes to the severity of several newborn conditions to the
extent that Saugstad coined the phrase "oxygen radical diseases of neonatology."
In order to counteract free radicals damage many strategies to augment
antioxidant status in ill-term and preterm infants have been proposed and several
medications have been experimented with mixed results. Several studies have
tested the efficacy of melatonin to counteract oxidative damage in diseases of
newborns such as chronic lung disease, perinatal brain injury, necrotizing
enterocolitis, and retinopathy of prematurity, giving promising results. The
peculiar perinatal susceptibility to oxidative stress indicates that prophylactic
use of antioxidants as melatonin could help to prevent or at least reduce
oxidative stress related diseases in newborns. However, more studies are needed
to confirm these beneficial effects.
PMID- 24349617
TI - Histone lysine demethylase (KDM) subfamily 4: structures, functions and
therapeutic potential.
AB - KDM4 histone demethylases catalyze the removal of methyl marks from histone
lysine residues to epigenetically regulate chromatin structure and gene
expression. KDM4 expression is tightly regulated to insure proper function in
diverse biological processes, such as cellular differentiation. Mounting evidence
has shown that disrupting KDM4 expression is implicated in the establishment and
progression of multiple diseases including cancer. In particular, genomic regions
encoding the KDM4A, B and C genes are often amplified, disrupting normal cellular
proliferation. Furthermore, KDM4 demethylases are promising druggable targets. In
this review, we highlight the latest advances in characterizing the structures
and regulatory mechanisms of KDM4 proteins, as well as our current understanding
of their alterations and roles in tumorigenesis. We also review the reported KDM4
inhibitors and discuss their potential as therapeutic agents.
PMID- 24349618
TI - Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and
corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in
skin lesions.
AB - BACKGROUND: Recent studies report independent associations between psoriasis,
cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from
activated myeloid cells is associated with CV risk mainly through lipid
oxidation, induction of endothelial dysfunction and release of IL-12 from
macrophages. OBJECTIVES: To elucidate associations between psoriasis and
conventional CV risk factors. METHODS: We performed a cross-sectional study of
100 psoriasis patients and 53 controls, group matched on age, gender and body
mass index, to assess levels of MPO in serum, as well as immunohistochemical
staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin.
RESULTS: Although the groups did not differ on waist circumference, glucose,
cholesterol, triglycerides, creatinine or personal history of CV events,
psoriasis patients had significantly higher waist-to-hip ratios, blood pressures,
proportion of current smokers, and lower high density lipoprotein level than
controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients,
even after adjusting for the CV risk factors on which the groups differed. MPO
did correlate with coronary artery calcification, carotid plaque, carotid intima
media thickness and flow mediated dilation, but did not correlate with psoriasis
severity. However, MPO was highly expressed in lesional psoriatic skin and
colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density
correlated with circulation MPO levels. CONCLUSION: Lesional skin CD11b(+)
leukocytes activated to generate MPO may contribute to serum levels of MPO.
Lesional CD11b(+) cell activity may be an alternative measure of disease burden
to PASI that underlies the MPO biomarker for systemic inflammation related to
Cardiovascular Disease.
PMID- 24349619
TI - Transcriptomic changes induced by mycophenolic acid in gastric cancer cells.
AB - BACKGROUND: Inhibition of inosine monophosphate dehydrogenase (IMPDH) by
mycophenolic acid (MPA) can inhibit proliferation and induce apoptosis in cancer
cells. This study investigated the underlying molecular mechanisms of MPA's
anticancer activity. METHODS: A gastric cancer cell line (AGS) was treated with
MPA and gene expression at different time points was analyzed using Illumina
whole genome microarrays and selected genes were confirmed by real-time RT-PCR.
RESULTS: Transcriptomic profiling identified 1070 genes with >=2 fold changes and
85 genes with >4 fold alterations. The most significantly altered biological
processes by MPA treatment include cell cycle, apoptosis, cell proliferation and
migration. MPA treatment altered at least ten KEGG pathways, of which eight (p53
signaling, cell cycle, pathways in cancer, PPAR signaling, bladder cancer,
protein processing in ER, small cell lung cancer and MAPK signaling) are cancer
related. Among the earliest cellular events induced by MPA is cell cycle arrest
which may be caused by six molecular pathways: 1) up-regulation of cyclins (CCND1
and CCNE2) and down-regulation of CCNA2 and CCNB1, 2) down-regulation of cyclin
dependent kinases (CDK4 and CDK5); 3) inhibition of cell division related genes
(CDC20, CDC25B and CDC25C) and other cell cycle related genes (MCM2, CENPE and
PSRC1), 4) activation of p53, which activates the cyclin-dependent kinase
inhibitors (CDKN1A), 5) impaired spindle checkpoint function and chromosome
segregation (BUB1, BUB1B, BOP1, AURKA, AURKB, and FOXM1); and 6) reduction of
availability of deoxyribonucleotides and therefore DNA synthesis through down
regulation of the RRM1 enzyme. Cell cycle arrest is followed by inhibition of
cell proliferation, which is mainly attributable to the inhibition of the
PI3K/AKT/mTOR pathway, and caspase-dependent apoptosis due to up-regulation of
the p53 and FAS pathways. CONCLUSIONS: These results suggest that MPA has
beneficial anticancer activity through diverse molecular pathways and biological
processes.
PMID- 24349620
TI - Genetic myostatin decrease in the golden retriever muscular dystrophy model does
not significantly affect the ubiquitin proteasome system despite enhancing the
severity of disease.
AB - Recent studies suggest that inhibiting the protein myostatin, a negative
regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne
muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden
retriever muscular dystrophy (GRMD) dog was bred with whippets having a
heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased
myostatin (GRippets) demonstrated an accelerated physical decline compared to
related affected GRMD dogs with full myostatin. To examine the role of the
ubiquitin proteasome and calpain systems in this accelerated decline, we
determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1,
RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and
calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis
muscles in control, affected GRMD, and GRippet dogs. While individual affected
GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin
ligase expression, neither group was significantly different from the control
group. The affected GRMD dogs demonstrated significant increases in caspase-like
and trypsin-like activity in the cranial sartorius; however, all three proteasome
activities in the GRippet muscles did not differ from controls. Increased
variability in calpain 1 and calpain 2 expression and activity in the affected
GRMD and GRippet groups were identified, but no statistical differences from the
control group were seen. These studies suggest a role of myostatin in the disease
progression of GRMD, which does not significantly involve key components of the
ubiquitin proteasome and calpain systems involved in the protein quality control
of sarcomere and other structural skeletal muscle proteins.
PMID- 24349621
TI - Pravastatin stimulates angiogenesis in a murine hindlimb ischemia model: a
positron emission tomography imaging study with (64)Cu-NOTA-TRC105.
AB - In this study, (64)Cu-NOTA-TRC105 (TRC105 is an anti-CD105 monoclonal antibody
that binds to both human and murine CD105) positron emission tomography (PET) was
used to assess the response to pravastatin treatment in a murine model of
peripheral artery disease (PAD). Hindlimb ischemia was induced by ligation of the
right femoral arteries in BALB/c mice under anesthesia, and the left hindlimb
served as an internal control. Mice in the treatment group were given
intraperitoneal pravastatin daily until the end of the study, whereas the animals
in the control group were injected with 0.9% sodium chloride solution. Laser
Doppler imaging showed that blood flow in the ischemic hindlimb plummeted to ~20%
of the normal level after surgery, and gradually recovered to near normal level
on day 10 in the treatment group and on day 20 in the control group. Angiogenesis
was non-invasively monitored and quantified with (64)Cu-NOTA-TRC105 PET on
postoperative days 3, 10, 17, and 24. Tracer uptake at 48 h post-injection in the
ischemic hindlimb in the treatment group was significantly higher than that of
the control group on day 10 (20.5 +/- 1.9 %ID/g vs 11.4 +/- 1.5 %ID/g),
suggesting increased CD105 expression and higher level of angiogenesis upon
pravastatin treatment, and gradually decreased to background levels in both
groups (4.9 +/- 0.8 %ID/g vs 3.4 +/- 1.9 %ID/g on day 24). The in vivo PET data
correlated well with ex vivo biodistribution studies performed on day 24.
Increased CD105 expression on days 3 and 10 following ischemia was further
confirmed by immunofluorescence staining. Taken together, our results indicated
that (64)Cu-NOTA-TRC105 PET is a suitable and non-invasive method to monitor the
angiogenesis and therapeutic response in PAD, which can also be utilized for non
invasive evaluation of other pro-angiogenic/anti-angiogenic drugs in other
cardiovascular diseases and cancer.
PMID- 24349622
TI - At pharmacologically relevant concentrations intravenous iron preparations cause
pancreatic beta cell death.
AB - BACK GROUND: Overt and subtle iron overload cause diabetes by lowering insulin
production and promoting insulin resistance. Via divalent metal transporters
pancreatic beta cells take up non-transferrin-bound iron which by catalyzing
Fenton reaction can cause oxidative stress. Due to their strict dependence on
mitochondrial glucose metabolism and limited antioxidant capacity, beta cells are
exquisitely vulnerable to oxidative stress and hence catalytically active iron.
Intravenous (IV) iron preparations are routinely used in the management of anemia
in patients with end stage renal disease. This has led to an epidemic of iron
overload in this population. This study explored the effect of pharmacologically
relevant concentrations of a commonly used IV iron preparation on the beta cells
in isolated pancreatic islets. METHODS: Isolated rat pancreatic islets were
incubated for 24 hours in culture media containing vehicle or pharmacologically
relevant concentration of ferric sucrose and examined for the extent of cell
death and oxidative stress. RESULTS: Exposure to iron sucrose resulted in a
concentration-dependent oxidative stress and pancreatic islet cell death
predominantly affecting beta cells. CONCLUSIONS: At pharmacologically-relevant
concentrations a commonly used IV iron preparation causes oxidative stress and
beta cell death. These findings suggest that indiscriminate use of IV iron may
impair insulin production capacity in ESRD patients the majority of whom have
Type-2 diabetes.
PMID- 24349623
TI - Serum miR-200c and clinical outcome of patients with advanced esophageal squamous
cancer receiving platinum-based chemotherapy.
AB - MicroRNA-200c (miR-200c) influences sensitivity to chemotherapy and radiotherapy
in vitro. This study was designed to investigate the prognostic potential of
serum miR-200c in patients with advanced esophageal squamous cancer (ESCC). The
serum levels of miR-200c was assayed by quantitative RT-PCR in 157 healthy
subjects and 157 patients with advanced ESCC who were treated with platinum-based
chemotherapy. The serum levels of miR-200c in advanced ESCC patients was
significantly increased compared with those in controls (P < 0.001). Serum miR
200c expression was significantly associated with TNM stage (P = 0.037) and
treatment response (P = 0.021). Patients with high expression of serum miR-200c
had a higher risk for death than those with low expression of serum miR-200c
(adjusted hazard ratios = 1.665, 95% confidence intervals: 1.135-2.443, P =
0.009). In conclusion, serum miR-200c may serve as predictor of survival for
advanced ESCC and provide information for personalized therapy in advanced ESCC.
PMID- 24349624
TI - Assessing the optimal dose for Cetrorelix in Chinese women undergoing ovarian
stimulation during the course of IVF-ET treatment.
AB - We conducted a prospective, randomized, and controlled trial to assess the
optimal dose for GnRH antagonist, cetrorelix, for Chinese women during the course
of ovarian stimulation. The patients were randomly divided into two groups, in
which 48 patients were advised to inject 0.25 mg Cetrorelix daily (the 0.25 mg
group), while 39 patients were instructed to receive a daily dose of 0.125 mg
cetrorelix (the 0.125 mg group). In general, a daily dose of 0.125 mg cetrorelix
could be more optimal for Chinese women as manifested by the lower cancellation
rate, higher implantation rate and clinical pregnancy rate. Specifically, daily
administration of 0.125 mg cetrorelix for patients under 35 years old is
associated with a 3-fold higher implantation rate and a 5-fold higher clinical
pregnancy rate as compared with that of those patients >= 35 years old. On the
contrary, higher rates for implantation and clinical pregnancy were noted by
daily injection of 0.25 mg cetrorelix in elder patients (>= 35 years old) as
compared with that of young patients (< 35 years old). Together, our data suggest
that a daily dose of 0.125 mg cetrorelix could be more optimal for patients < 35
years old, while 0.25 mg/day of cetrorelix are likely conducive to higher
implantation and clinical pregnancy rate for those patients >= 35 years old.
These data could be important for preventing LH surge while maintaining optimal
LH levels necessary for embryo implantation for Chinese women during the course
of IVF-ET treatment.
PMID- 24349625
TI - Hormonal replacement treatment improves clinical pregnancy in frozen-thawed
embryos transfer cycles: a retrospective cohort study.
AB - This study aimed to assess frozen-thawed embryo transfer (FET) outcomes in
natural, hormone replacement treatment (HRT) and semi-HRT cycles. This was a
retrospective cohort study of 5414 cycles of patients in an academic hospital.
Patients were grouped as 2216 natural cycles, 1180 semi-HRT cycles, and 2018 HRT
cycles. Primary outcome measures were implantation rate, clinical pregnancy rate
and live birth rate. Other parameters, such as peak endometria-thickness, were
also analyzed. Patients undergoing FET with HRT obtained higher implantation rate
and clinical pregnancy rate than patients with natural or semi-HR cycles (29.3%
vs. 21.5% vs. 25.6%, P=0.01, and 48.7% vs. 42.7% vs. 36.1%, P=0.01,
respectively). This finding was not changed in patients with thin endometrium
(<=8 mm). A Subanalysis in patients with HRT showed that the implantation and
clinical pregnancy rate was higher in patients without ovulation than ovulatory
patients (29.8% vs. 16.9%, P<0.01, and 49.5% vs. 26.3%, P<0.01, respectively).
This study suggests that HRT increases the possibility of pregnancy. Further, our
data showed that ovulation in HRT cycle has a detrimental effect on pregnancy.
Therefore, we recommend that HRT should be used in FET cycles, and ovulation of
patients should be evaluated during the treatment.
PMID- 24349626
TI - Cardiovascular autonomic dysfunction in primary ovarian insufficiency: clinical
and experimental evidence.
AB - OBJECTIVE: Women with primary ovarian insufficiency (POI) present an increased
risk for cardiovascular disease. In this study we tested the hypothesis that POI
in women under hormone therapy (HT) are associated with vascular vasodilatation
attenuation and cardiovascular autonomic dysfunction and these impairments are
related to changes in systemic antioxidant enzymes. Furthermore, the possibility
that ovarian hormone deprivation can induce such changes and that HT cannot
reverse all of those impairments was examined in an experimental model of POI.
METHODS: Fifteen control and 17 patients with primary ovarian insufficiency
receiving HT were included in the study. To test the systemic and cardiac
consequences of ovarian hormone deprivation, ovariectomy was induced in young
female rats that were submitted or not to HT. Spectral analysis of RR interval
and blood pressure signals were performed and oxidative stress parameters were
determined. RESULTS: POI women under HT have increased mean arterial pressure
(94+/-10 vs. 86+/-5 mmHg) despite normal endothelial and autonomic modulation of
vasculature. Additionally, they presented impaired baroreflex sensitivity (3.9+/
1.38 vs. 7.15+/-3.62 ms/mmHg) and reduced heart rate variability (2310+/-1173 vs.
3754+/-1921 ms(2)). Similar results obtained in ovariectomized female rats were
accompanied by an increased lipoperoxidation (7433+/-1010 vs. 6180+/-289 cps/mg
protein) and decreased antioxidant enzymes in cardiac tissue. As it was observed
in women, the HT in animals did not restore hemodynamic and autonomic
dysfunctions. CONCLUSION: These data provide clinical and experimental evidence
that long term HT may not restore all cardiovascular risk factors associated with
ovarian hormone deprivation.
PMID- 24349627
TI - Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor
tissue specimens can be reversed by BR-DIM treatment.
AB - Androgen Receptor (AR) signaling is critically important during the development
and progression of prostate cancer (PCa). The AR signaling is also important in
the development of castrate resistant prostate cancer (CRPC) where AR is
functional even after androgen deprivation therapy (ADT); however, little is
known regarding the transcriptional and functional regulation of AR in PCa.
Moreover, treatment options for primary PCa for preventing the occurrence of CRPC
is limited; therefore, novel strategy for direct inactivation of AR is urgently
needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue
specimens, especially in patients with higher Gleason grade tumors, consistent
with increased expression of AR. Forced over-expression of miR-34a in PCa cell
lines led to decreased expression of AR and prostate specific antigen (PSA) as
well as the expression of Notch-1, another important target of miR-34a. Most
importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy
showed reexpression of miR-34a, which was consistent with decreased expression of
AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to
nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated
with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter
concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells.
These results suggest, for the first time, epigenetic silencing of miR-34a in
PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful
for the inactivation of AR in the treatment of PCa.[This corrects the article on
p. 14 in vol. 4.].
PMID- 24349628
TI - Speech and Language Impairments in Autism: Insights from Behavior and
Neuroimaging.
AB - A failure to develop language is one of the earliest signs of autism. The ability
to identify the neural signature of this deficit in very young children has
become increasingly important, given that the presence of speech before five
years of age is the strongest predictor for better outcomes in autism. This
review consolidates what is known about verbal and preverbal precursors of
language development as a framework for examining behavioral and brain anomalies
related to speech and language in autism spectrum disorders. Relating the
disruptions in the speech network to the social deficits observed will provide
promising targets for behavioral and pharmacological interventions in ASD.
PMID- 24349629
TI - Monographs editor.
PMID- 24349630
TI - JNK Signaling Network and Cancer.
PMID- 24349631
TI - Mixed Lineage Kinase-c-Jun N-Terminal Kinase Axis: A Potential Therapeutic Target
in Cancer.
AB - Mixed lineage kinases (MLKs) are members of the mitogen-activated protein kinase
kinase kinase (MAP3K) family and are reported to activate MAP kinase pathways.
There have been at least 9 members of the MLK family identified to date, although
the physiological functions of all the family members are yet unknown. However,
MLKs in general have been implicated in neurodegenerative diseases, including
Parkinson and Alzheimer diseases. Recent reports suggest that some of the MLK
members could play a role in cancer via modulating cell migration, invasion, cell
cycle, and apoptosis. This review article will first describe the biology of MLK
members and then discuss the current progress that relates to their functions in
cancer.
PMID- 24349633
TI - Linking JNK Activity to the DNA Damage Response.
AB - The activity of c-Jun N-terminal kinase (JNK) was initially described as
ultraviolet- and oncogene-induced kinase activity on c-Jun. Shortly after this
initial discovery, JNK activation was reported for a wider variety of DNA
damaging agents, including gamma-irradiation and chemotherapeutic compounds. As
the DNA damage response mechanisms were progressively uncovered, the mechanisms
governing the activation of JNK upon genotoxic stresses became better understood.
In particular, a recent set of papers links the physical breakage in DNA, the
activation of the transcription factor NF-kappaB, the secretion of TNF-alpha, and
an autocrine activation of the JNK pathway. In this review, we will focus on the
pathway that is initiated by a physical break in the DNA helix, leading to JNK
activation and the resultant cellular consequences. The implications of these
findings will be discussed in the context of cancer therapy with DNA-damaging
agents.
PMID- 24349634
TI - RACK1 Function in Cell Motility and Protein Synthesis.
AB - The receptor for activated C kinase 1 (RACK1) serves as an adaptor for a number
of proteins along the MAPK, protein kinase C, and Src signaling pathways. The
abundance and near ubiquitous expression of RACK1 reflect its role in
coordinating signaling molecules for many critical biological processes, from
mRNA translation to cell motility to cell survival and death. Complete deficiency
of Rack1 is embryonic lethal, but the recent development of genetic Rack1
hypomorphic mice has highlighted the central role that RACK1 plays in cell
movement and protein synthesis. This review focuses on the importance of RACK1 in
these processes and places the recent work in the larger context of understanding
RACK1 function.
PMID- 24349632
TI - Role of p38 MAP Kinase Signal Transduction in Solid Tumors.
AB - Mitogen-activated protein kinases (MAPKs) mediate a wide variety of cellular
behaviors in response to extracellular stimuli. One of the main subgroups, the
p38 MAP kinases, has been implicated in a wide range of complex biologic
processes, such as cell proliferation, cell differentiation, cell death, cell
migration, and invasion. Dysregulation of p38 MAPK levels in patients are
associated with advanced stages and short survival in cancer patients (e.g.,
prostate, breast, bladder, liver, and lung cancer). p38 MAPK plays a dual role as
a regulator of cell death, and it can either mediate cell survival or cell death
depending not only on the type of stimulus but also in a cell type specific
manner. In addition to modulating cell survival, an essential role of p38 MAPK in
modulation of cell migration and invasion offers a distinct opportunity to target
this pathway with respect to tumor metastasis. The specific function of p38 MAPK
appears to depend not only on the cell type but also on the stimuli and/or the
isoform that is activated. p38 MAPK signaling pathway is activated in response to
diverse stimuli and mediates its function by components downstream of p38.
Extrapolation of the knowledge gained from laboratory findings is essential to
address the clinical significance of p38 MAPK signaling pathways. The goal of
this review is to provide an overview on recent progress made in defining the
functions of p38 MAPK pathways with respect to solid tumor biology and generate
testable hypothesis with respect to the role of p38 MAPK as an attractive target
for intervention of solid tumors.
PMID- 24349635
TI - c-Jun N-Terminal Kinases Mediate a Wide Range of Targets in the Metastatic
Cascade.
AB - Disseminated cancer cells rely on intricate interactions among diverse cell types
in the tumor-associated stroma, vasculature, and immune system for survival and
growth. Ubiquitous expression of c-Jun N-terminal kinase (jnk) genes in various
cell types permits their control of metastasis. In early stages of metastasis,
JNKs affect tumor-associated inflammation and angiogenesis as well as tumor cell
migration and intravasation. Within the tumor stroma, JNKs are essential for the
release of growth factors that promote epithelial-to-mesenchymal transition (EMT)
in tumor cells. JNK3, the least ubiquitous isoform, facilitates angiogenesis by
increasing endothelial cell migration. Importantly, JNK expression in tumor cells
integrates stromal signals to promote tumor cell invasion. However, JNK isoforms
differentially regulate migration toward the endothelial barrier. Once tumor
cells enter the bloodstream, JNKs increase circulating tumor cell (CTC) survival
and homing to tissues. By promoting fibrosis, JNKs improve CTC attachment to the
endothelium. Once anchored, JNKs stimulate EMT to facilitate tumor cell
extravasation and enhance the secretion of endothelial barrier disrupters. Tumor
cells attract barrier-disrupting macrophages by JNK-dependent transcription of
macrophage chemoattractant molecules. In the secondary tissue, JNKs are
instrumental in the premetastatic niche and stimulate tumor cell proliferation.
JNK expression in cancer cells stimulates tissue-remodeling macrophages to
improve tumor colonization. However, in T-cells, JNKs alter cytokine production
that increases tumor surveillance and inhibits the recruitment of tissue
remodeling macrophages. Therapeutically targeting JNKs for metastatic disease is
attractive considering their promotion of metastasis; however, specific JNK tools
are needed to determine their definitive actions within the context of the entire
metastatic cascade.
PMID- 24349636
TI - JNK Signaling in the Control of the Tumor-Initiating Capacity Associated with
Cancer Stem Cells.
AB - Deregulation of c-Jun NH2-terminal kinase (JNK) signaling occurs frequently in a
variety of human cancers, yet the exact role(s) of JNK deregulation in cancer
cell biology remains to be fully elucidated. Our recent demonstration that the
activity of JNK is required not only for self-renewal of glioma stem cells but
also for their tumor initiation has, however, identified a new role for JNK in
the control of the stemness and tumor-initiating capacity of cancer cells.
Significantly, transient JNK inhibition was sufficient to cause sustained loss of
the tumor-initiating capacity of glioma stem cells, suggesting that the phenotype
of "lost tumor-initiating capacity" may be as stable as the differentiated state
and that the tumor-initiating capacity might therefore be under the control of
JNK through an epigenetic mechanism that also governs stemness and
differentiation. Here, in this article, we review the role and mechanism of JNK
in the control of this "stemness-associated tumor-initiating capacity" (STATIC),
a new hypothetical concept we introduce in this review article. Since the idea of
STATIC is essentially applicable to both cancer types that do and do not follow
the cancer stem cell hypothesis, we also give consideration to the possible
involvement of JNK-mediated control of STATIC in a wide range of human cancers in
which JNK is aberrantly activated. Theoretically, successful targeting of STATIC
through JNK could contribute to long-term control of cancer. Issues to be
considered before clinical application of therapies targeting this JNK-STATIC
axis are also discussed.
PMID- 24349637
TI - The 2 Faces of JNK Signaling in Cancer.
AB - c-Jun NH2-terminal kinase (JNK) was discovered almost 20 years ago as the protein
kinase responsible for phosphorylating c-Jun at Ser-63 and Ser-73. These sites
had previously been demonstrated to be essential for the stimulation of c-Jun
activity and for cooperation with Ha-ras in oncogenic transformation. This led to
the idea that JNK was a positive regulator of cellular transformation. However,
the analysis of jnk gene deletion in various mouse models of cancer has produced
conflicting findings, with some studies supporting the pro-oncogenic function of
JNK and others providing evidence that JNK acts as a tumor suppressor. This
review will discuss how these unexpected findings have increased our
understanding of the role of JNK signaling in cancer and have provided a source
of new working hypotheses.
PMID- 24349638
TI - Mitogen-activated protein kinases and their role in radiation response.
AB - Ionizing radiation, like a variety of other cellular stress factors, can activate
or down-regulate multiple signaling pathways, leading to either increased cell
death or increased cell proliferation. Modulation of the signaling process,
however, depends on the cell type, radiation dose, and culture conditions. The
mitogen-activated protein kinase (MAPK) pathway transduces signals from the cell
membrane to the nucleus in response to a variety of different stimuli and
participates in various intracellular signaling pathways that control a wide
spectrum of cellular processes, including growth, differentiation, and stress
responses, and is known to have a key role in cancer progression. Multiple signal
transduction pathways stimulated by ionizing radiation are mediated by the MAPK
superfamily including the extracellular signal-regulated kinase (ERK), c-Jun N
terminal kinase (JNK), and p38 MAPK. The ERK pathway, activated by mitogenic
stimuli such as growth factors, cytokines, and phorbol esters, plays a major role
in regulating cell growth, survival, and differentiation. In contrast, JNK and
p38 MAPK are weakly activated by growth factors but respond strongly to stress
signals including tumor necrosis factor (TNF), interleukin-1, ionizing and
ultraviolet radiation, hyperosmotic stress, and chemotherapeutic drugs.
Activation of JNK and p38 MAPK by stress stimuli is strongly associated with
apoptotic cell death. MAPK signaling is also known to potentially influence tumor
cell radiosensitivity because of their activity associated with radiation-induced
DNA damage response. This review will discuss the MAPK signaling pathways and
their roles in cellular radiation responses.
PMID- 24349639
TI - Network Motifs in JNK Signaling.
AB - Multiple growth factors and extracellular signals can lead to activation of the c
Jun amino N-terminal protein kinase (JNK) pathway. Activation of JNK can in turn
lead to a multitude of downstream changes in phosphorylation and transcriptional
activation within the cell. Mapping the upstream and downstream connectivity
within the JNK network reveals an enrichment of bi-fan and feed-forward network
motifs formed immediately upstream and downstream of JNK. In addition, negative
feedback loops also exist through transcriptional activation of phosphatases that
target the JNK pathway. The combinations of these motifs allow flexibility and
tunability in signal integration and processing within the JNK network and may
confer the wide range of biological responses that can be regulated by JNK
activation. In this review, we highlight the pathways and motifs leading to JNK
activation and its downstream signaling as well as the complexity in isoforms
within this network.
PMID- 24349640
TI - The Implementation of a Telephone-Delivered Intervention for Asian American
Disordered Gamblers: A Pilot Study.
AB - This report will discuss the implementation and preliminary results of a
community-based telephone-delivered gambling treatment program specifically
designed for Asian Americans. The intervention was implemented by the NICOS
Chinese Health Coalition, a nonprofit community organization based in Northern
California, overseen by the UCLA (University of California, Los Angeles) Gambling
Studies Program and the California Office of Problem Gambling, and launched in
December 2010. It consisted of six 1-hr long telephone-delivered sessions
conducted by a mental health provider using a translated version of the Freedom
from Problem Gambling Self-Help Workbook. In the current study, 6 providers
completed a 30-hr training program for gambling related disorders. One-hundred
and 40 callers inquired about the intervention within the first 6 months of its
launch, 19 clients expressed interest in participating, and 8 enrolled into the
program. The results show that the majority of clients who enrolled into the
program did not report any gambling behavior after baseline and improved on self
reported measures of overall life satisfaction, gambling urges, and self-control.
This study suggests that the implementation of this type of intervention is
feasible at a small community-based organization and may be effective in treating
gambling-related disorders for Asian American populations. The low rate of
clientele enrollment is addressed and potential remedies are discussed.
PMID- 24349641
TI - Effects of the Arg-Pro and Gly-Gly-Nle Moieties on Melanocortin-1 Receptor
Binding Affinities of alpha-MSH Peptides.
AB - The purpose of this study was to examine the effects of the -Arg-Pro-(RP) and
Gly-Gly-Nle- (GGNle) moieties on the melanoma targeting and clearance properties
of 99mTc-peptides. We synthesized four new peptides {Ac-GGNle-CCEHdFRWC-NH2, Ac
GGNle-CCEHdFRWCRP-NH2, Ac-CCEHdFRWC-NleGG-NH2 and Ac-CCEHdFRWCRP-NleGG-NH2} and
determined their melanocortin-1 (MC1) receptor binding affinities in B16/F1
melanoma cells. Then we further examined the biodistribution properties of 99mTc
Ac-GGNle-CCEHdFRWCRP-NH2 and 99mTc-Ac-CCEHdFRWCRP-NleGG-NH2 in B16/F1 melanoma
bearing C57 mice. Overall, the Arg-Pro motif was critical for retaining low
nanomolar MC1 receptor binding affinity. The deletion of the -RP- moiety
dramatically reduced the receptor binding affinities of the peptides. The N
terminus was a better position than C-terminus for the -GGNle- moiety in
retaining the lower renal and liver uptake. High melanoma uptake coupled with
fast urinary clearance of 99mTc-Ac-GGNle-CCEHdFRWCRP-NH2 provided a new insight
into the design of new alpha-melanocyte stimulating hormone (alpha-MSH) peptides.
PMID- 24349642
TI - Protein-Ligand Interactions: Thermodynamic Effects Associated with Increasing the
Length of an Alkyl Chain.
AB - Thermodynamic parameters were determined for complex formation between the Grb2
SH2 domain and tripeptides of the general form Ac-pTyr-Xaa-Asn in which the Xaa
residue bears a linear alkyl chain varying in length from 1-5 carbon atoms.
Binding affinity increases upon adding a methylene group to the Ala derivative,
but further chain extension gives no extra enhancement in potency. The
thermodynamic signatures of the ethyl and n-propyl derivatives are virtually
identical as are those for the n-butyl and n-pentyl analogs. Crystallographic
analysis of the complexes reveals a high degree of similarity in the structure of
the domain and the bound ligands with the notable exception that there is a
gauche interaction in the side chains in the bound conformations of ligands
having n-propyl, n-butyl, and n-pentyl groups. However, eliminating this
unfavorable interaction by introducing a Z-double bond into the side chain of the
n-propyl analog does not result in an increase in affinity. Increases in the
amount of nonpolar surface that is buried upon ligand binding correlate with
favorable changes in DeltaH degrees , but these are usually offset by
corresponding unfavorable changes in -TDeltaS degrees ; there is little
correlation of DeltaCp with changes in the amount of buried nonpolar surface.
PMID- 24349643
TI - Diagnostic neuroradiology for the interventional neuroradiologist.
AB - In order to further improve the impact of the continuously evolving
neurointerventional techniques, the interventional neuroradiologist needs to have
at his disposal more powerful techniques to image the central nervous system.
With the recent development of diagnostics techniques that are computed
tomography and magnetic resonance based we are now able to assess not just
morphology, but also physiology, physiopathology and function. This review
discusses the place of diagnostic techniques in the evaluation that the
interventional neuroradiologist hast to make when confronted with patients. We
provide an overview of current techniques for the brain and spine.
PMID- 24349644
TI - Screening and early diagnosis of osteoporosis through X-ray and ultrasound based
techniques.
AB - Effective prevention and management of osteoporosis would require suitable
methods for population screenings and early diagnosis. Current clinically
available diagnostic methods are mainly based on the use of either X-rays or
ultrasound (US). All X-ray based methods provide a measure of bone mineral
density (BMD), but it has been demonstrated that other structural aspects of the
bone are important in determining fracture risk, such as mechanical features and
elastic properties, which cannot be assessed using densitometric techniques.
Among the most commonly used techniques, dual X-ray absorptiometry (DXA) is
considered the current "gold standard" for osteoporosis diagnosis and fracture
risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific
limitations (e.g., use of ionizing radiation, large size of the equipment, high
costs, limited availability) that hinder its application for population
screenings and primary care diagnosis. This has resulted in an increasing
interest in developing reliable pre-screening tools for osteoporosis such as
quantitative ultrasound (QUS) scanners, which do not involve ionizing radiation
exposure and represent a cheaper solution exploiting portable and widely
available devices. Furthermore, the usefulness of QUS techniques in fracture risk
prediction has been proven and, with the last developments, they are also
becoming a more and more reliable approach for assessing bone quality. However,
the US assessment of osteoporosis is currently used only as a pre-screening tool,
requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here
we illustrate the state of art in the early diagnosis of this "silent disease"
and show up recent advances for its prevention and improved management through
early diagnosis.
PMID- 24349645
TI - Magnetically-coated silica nanospheres for dual-mode imaging at low ultrasound
frequency.
AB - AIM: To experimentally investigate the acoustical behavior of different dual-mode
nanosized contrast agents (NPCAs) for echographic medical imaging at low
ultrasound (US) frequency. METHODS: We synthesized three different nanosized
structures: (1) Pure silica nanospheres (SiNSs); (2) FePt-iron oxide (FePt-IO)
coated SiNSs; and (3) IO-coated SiNSs, employing three different diameter of SiNS
core (160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel
solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were
insonified by a commercial echographic system at three different low US pulse
values (2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from
each considered NPCA containing sample, has been processed in order to calculate
the US average backscatter intensity and compare the acoustic behavior of the
different NPCA types. RESULTS: The highest US contrast was exhibited by pure
SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure
SiNSs with a slight difference in terms of brightness values. The acoustic
response of the examined NPCAs resulted function of both SiNS diameter and US
frequency. Specifically, higher US frequencies determined higher value of the
backscatter for a given SiNS diameter. Frequency-dependent enhancement was marked
for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO
coated SiNSs resulted almost unaffected by such frequency variations. Pure and
FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter
up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed
the lowest acoustical response for each synthesized diameter and employed US
frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION:
The US characterization of magnetically covered SiNS shows that FePt-IO, rather
than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode
imaging of deep organs, combining US and magnetic resonance imaging.
PMID- 24349646
TI - CT dose and image quality in the last three scanner generations.
AB - AIM: To compare the computed tomography (CT) dose and image quality with the
filtered back projection against the iterative reconstruction and CT with a
minimal electronic noise detector. METHODS: A lung phantom (Chest Phantom N1 by
Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation,
the Definition Flash and the Definition Edge (all from Siemens, Erlangen,
Germany). The scan parameters were identical to the Siemens presetting for THORAX
ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were
examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100,
50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were
reconstructed using classic filtered back projection. Iterative reconstruction
(SAFIRE, level 3) was performed for the two other scanners. A Stellar detector
was used with the Somatom Definition Edge. The CT doses were represented by the
dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast,
noise and subjective image quality were recorded by two different radiologists
with 10 and 3 years of experience in chest CT radiology. To determine the average
dose reduction between two scanners, the integral of the dose difference was
calculated from the lowest to the highest noise level. RESULTS: When using
iterative reconstruction (IR) instead of filtered back projection (FBP), the
average dose reduction was 30%, 52% and 80% for bone, soft tissue and air,
respectively, for the same image quality (P < 0.0001). The recently introduced
Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and
70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose
reduction was larger at lower dose levels. With the same radiation dose, an
average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by
changing from FBP to IR and from IR to Sd, respectively. For the same contrast to
noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was
produced for IR and Sd, respectively. For the same subjective image quality, the
dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd,
respectively. CONCLUSION: This study showed an average dose reduction between 27%
and 70% for the new Stellar detector, which is equivalent to using IR instead of
FBP.
PMID- 24349647
TI - New generation aspiration catheter: Feasibility in the treatment of pulmonary
embolism.
AB - AIM: To report our preliminary experience with a new generation aspiration
catheter in the treatment of symptomatic pulmonary embolism (PE). METHODS: A
retrospective database search for pulmonary artery embolectomy since introduction
of the Pronto .035" and XL extraction catheter (Vascular Solutions, Minneapolis,
MN) at our institution in 10/2009 was performed. Ten consecutive patients were
identified in which the Pronto .035" or XL catheter was used between 01/2010 and
03/2013. All patients were referred for catheter based embolectomy due to
contraindications to systemic lysis, or for being in such a critical clinical
condition that immediate percutaneous treatment deemed warranted. The computed
tomography (CT) right to left heart ratio as predictor for the severity of the PE
was retrospectively evaluated on standard axial views. The difference between pre
and post-procedure pulmonary pressure measures was taken to assess the
procedural effect. RESULTS: Extensive PE was confirmed angiographically in all
patients. Measured right- to left ventricle (RV/LV) ratios were elevated beyond
one in seven of the eight available CTs. Acute procedural success defined as
clinical removal of visible thrombus and improvement in mean pulmonary artery
pressure was seen in all recorded patients (n = 8), the mean pulmonary pressures
declined from a median (range) of 35.5 (19-46) to 23 (10-37, P = 0.008) mmHg.
Neither death nor other complications occurred intra- or immediately
periprocedural, yet short term mortality within 30 d was found in 6 out of 9
patients, one patient was lost in follow up. The cause of death within 30 d in
the 6 patients was identified as: Circulatory failure in direct connection with
the PE (n = 2), stroke, sepsis, or succumbing to malignancy in a hospice setting
(n = 2). CONCLUSION: Success in thrombus removal with improved pulmonary
hypertension and systemic hypotension suggests this aspiration technique to be
effective. Aspiration catheters should be part of further trials.
PMID- 24349648
TI - MDCT imaging following nephrectomy for renal cell carcinoma: Protocol
optimization and patterns of tumor recurrence.
AB - The purpose of this pictorial essay is to review the common and uncommon sites of
renal cell carcinoma recurrence throughout the body by examining their
appearances on computerized tomography (CT). CT imaging protocols will be
discussed. The sites of recurrence have been categorized into 4 groups: chest and
mediastinum, abdomen and pelvis, musculoskeletal, and neurological. For each site
of recurrence, a representative CT image correlate with discussion is provided.
The unique CT appearance of renal cell carcinoma recurrence and how it can be
used in lesion detection will be discussed. Renal cell carcinoma recurrences are
hypervascular like the primary tumor, which can aid in not only lesion detection
but also in some cases, differentiation from other primary tumors. Through CT
case review of various sites of recurrence, lesions are shown to be easily seen
on arterial phase while sometimes being nearly inconspicuous on venous or delayed
phases. Coronal and sagittal reconstructions can also improve diagnostic
sensitivity. CT is the most commonly used imaging tool for surveillance of renal
cell carcinoma recurrence after nephrectomy. Knowledge of sites of recurrence as
well as the utility of arterial phase imaging and multiplanar reconstructions
will aid in optimizing detection of disease recurrence.
PMID- 24349649
TI - Mesenteric myolipoma.
AB - The authors report on a case of benign myolipoma (synonym lipoleiomyoma) which
was first described in 1991. The benign soft tissue tumor is composed of smooth
muscle and adipose tissue and occurs sporadically in different locations. In the
available literature cases were described retroperitoneal, spinal, orbital and
subcutaneous and mostly have been discovered in females. Characteristically
myolipomas are very large at diagnosis and reach diameters of 7 to 30 cm
particularly in peritoneal or retroperitoneal localization. The sometimes
enormous size leads to a displacing growth pattern which ultimately leads to the
clinical symptoms. The patients often complain of nonspecific, mostly painless
abdominal or thoracic pressure. Bordered by an intact capsule the tumors show no
signs of malignancy and in the available literature there is no evidence of
metastatic seeding. To the best of our knowledge the presented case is the first
description of a diffuse mesenteric myolipoma in a male individual. In this
article, we present the multidetector computed tomographic image characteristics,
macroscopic appearance and histopathological findings.
PMID- 24349650
TI - The economic burden of epilepsy in Korea, 2010.
AB - OBJECTIVES: The purposes of this study were to evaluate the prevalence of
epilepsy and to estimate the cost of epilepsy in Korea, 2010. METHODS: This study
used a prevalence based approach to calculate the cost of epilepsy. Claims data
from the Korean national health insurance and data from the Korea health panel,
the Korea National Statistical Office's records of causes of death, and labor
statistics were used to estimate the cost of epilepsy. Patients were defined as
those who were hospitalized or visited an outpatient clinic during 2010 with a
diagnosis of epilepsy (International Classification of Diseases 10th revision
codes G40-G41). Total costs of epilepsy included direct medical costs, direct non
medical cost and indirect costs. RESULTS: The annual prevalence of treated
epilepsy was 228 per 100 000 population, and higher in men. The age-specific
prevalence was highest for teenagers. The total economic burden of epilepsy was
536 billion Korean won (KW). Indirect cost (304 billion KW) was 1.3 times greater
than direct cost (232 billion KW). By gender, the male (347 billion KW) were more
burdened than the female (189 billion KW). The estimated cost in young age
younger than 20 years old was 24.5% of the total burden of epilepsy. CONCLUSIONS:
A significant portion of the economic burden of epilepsy is borne by people in
young age. To reduce the economic burden of epilepsy, effective prevention and
treatment strategies are needed.
PMID- 24349651
TI - Determinants of health care expenditures and the contribution of associated
factors: 16 cities and provinces in Korea, 2003-2010.
AB - OBJECTIVES: The purpose of this study was to classify determinants of cost
increases into two categories, negotiable factors and non-negotiable factors, in
order to identify the determinants of health care expenditure increases and to
clarify the contribution of associated factors selected based on a literature
review. METHODS: The data in this analysis was from the statistical yearbooks of
National Health Insurance Service, the Economic Index from Statistics Korea and
regional statistical yearbooks. The unit of analysis was the annual growth rate
of variables of 16 cities and provinces from 2003 to 2010. First, multiple
regression was used to identify the determinants of health care expenditures. We
then used hierarchical multiple regression to calculate the contribution of
associated factors. The changes of coefficients (R(2)) of predictors, which were
entered into this analysis step by step based on the empirical evidence of the
investigator could explain the contribution of predictors to increased medical
cost. RESULTS: Health spending was mainly associated with the proportion of the
elderly population, but the Medicare Economic Index (MEI) showed an inverse
association. The contribution of predictors was as follows: the proportion of
elderly in the population (22.4%), gross domestic product (GDP) per capita
(4.5%), MEI (-12%), and other predictors (less than 1%). CONCLUSIONS: As Baby
Boomers enter retirement, an increasing proportion of the population aged 65 and
over and the GDP will continue to increase, thus accelerating the inflation of
health care expenditures and precipitating a crisis in the health insurance
system. Policy makers should consider providing comprehensive health services by
an accountable care organization to achieve cost savings while ensuring high
quality care.
PMID- 24349652
TI - Cancer incidence in Korean Vietnam veterans during 1992-2003: the Korean veterans
health study.
AB - OBJECTIVES: The aim of this study was to investigate the association between
Vietnam experience including exposure to military herbicides and cancer incidence
in Korean Vietnam War veterans. METHODS: The cancer cases of 185 265 Vietnam
veterans from January 1, 1992 to December 31, 2003 were confirmed from the Korea
National Cancer Incidence Database. The age-adjusted incidence and standardized
incidence ratios (SIRs) were calculated using the male population during 1992 to
2003 as a standard population. RESULTS: The age-adjusted overall cancer incidence
per 100 000 person-years was 455.3 in Vietnam veterans. The overall cancer
incidence was slightly yet significantly lower in veterans (SIR, 0.97; 95%
confidence interval, 0.95 to 0.99) than in the general population. The overall
cancer incidence in enlisted soldiers was not lower (SIR, 1.00), whereas that in
officers was significantly lower (SIR, 0.87) than in the general population. The
incidences of prostate cancer and T-cell lymphoma in all veterans, and lung
cancer and bladder cancer in enlisted soldiers, and colon cancer and kidney
cancer in non-commissioned officers, and colon cancer, kidney cancer, and
prostate cancer in officers, were higher than in the general population. The SIR
for overall cancer among Vietnam veterans rose from 0.92 for 1992-1997 to 0.99
for 1998-2003. CONCLUSIONS: The overall cancer incidence in Vietnam veterans was
not higher than in the general male population. Vietnam veterans and military
rank subcohorts experienced a higher incidence of several cancers, including
prostate cancer, T-cell lymphoma, lung cancer, bladder cancer, kidney cancer, and
colon cancer than the general population. The SIR for overall cancer increased
over time in Vietnam veterans.
PMID- 24349654
TI - Relationship between current sleep duration and past suicidal ideation or attempt
among Korean adolescents.
AB - OBJECTIVES: To comprehensively examine the relationship between current sleep
duration and past suicidal idea or attempt among Korean adolescents. METHODS:
Data came from the 2009 Korea Youth Risk Behavior Web-based Survey with 75 066
participants (with the participation rate of 97.6%) in 800 middle and high
schools. Binary logistic regression was conducted by gender and depressed mood to
identify significant factors for suicidal ideation/attempt. The dependent
variable was the log odds of suicidal ideation/attempt, while the
independent/control variables were sleep duration and other demographic, socio
economic and health-related factors. RESULTS: A negative association between
sleep duration and suicidal ideation or attempt was weaker for those with
depressed mood than for those without such experience in Korea for Year 2009. The
odds ratio of suicidal ideation/attempt regarding less than 4 hours of sleep
compared to 6 to 7 hours of sleep, was smaller in a group with depressed mood
than in a group without such experience, for example, 1.64 (95% confidence
interval [CI], 1.29 to 2.08) vs. 2.06 (95% CI, 1.34 to 3.17) for men's suicidal
ideation, 2.50 (95% CI, 1.69 to 3.69) vs. 3.89 (95% CI, 1.74 to 8.66) for men's
suicidal attempt. A negative association between age (or self-rated health) and
suicidal ideation/attempt was also weaker for those with depressed mood than for
those without such experience in the nation for the year. CONCLUSIONS: There was
a negative association between sleep duration and suicidal ideation/attempt in
Korea for Year 2009 and this association was weaker for those with depressed mood
than for those without such experience. Based on the findings of this study,
adolescents' better mental health and longer, more comfortable sleep might help
to prevent their suicidal ideation and attempt in Korea.
PMID- 24349653
TI - Cardiovascular health metrics and all-cause and cardiovascular disease mortality
among middle-aged men in Korea: the Seoul male cohort study.
AB - OBJECTIVES: This study estimated the association of cardiovascular health
behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality
in middle-aged men in Korea. METHODS: In total, 12 538 men aged 40 to 59 years
were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics
defined the following lifestyle behaviors proposed by the American Heart
Association: smoking, physical activity, body mass index, diet habit score, total
cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health
metrics score was calculated as a single categorical variable, by assigning 1
point to each ideal healthy behavior. A Cox proportional hazards regression model
was used to estimate the hazard ratio of cardiovascular health behavior.
Population attributable risks (PARs) were calculated from the significant
cardiovascular health metrics. RESULTS: There were 1054 total and 171 CVD deaths
over 230 690 person-years of follow-up. The prevalence of meeting all 7
cardiovascular health metrics was 0.67%. Current smoking, elevated blood
pressure, and high fasting blood glucose were significantly associated with all
cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined
were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0
to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard
ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were
0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to
0.29) for CVD mortality. CONCLUSIONS: Among cardiovascular health behaviors, not
smoking, normal blood pressure, and recommended fasting blood glucose levels were
associated with reduced risks of all-cause and CVD mortality. Meeting a greater
number of cardiovascular health metrics was associated with a lower risk of all
cause and CVD mortality.
PMID- 24349655
TI - Social network characteristics and body mass index in an elderly Korean
population.
AB - OBJECTIVES: Research has shown that obesity appears to spread through social
ties. However, the association between other characteristics of social networks
and obesity is unclear. This study aimed to identify the association between
social network characteristics and body mass index (BMI, kg/m(2)) in an elderly
Korean population. METHODS: This cross-sectional study analyzed data from 657
Koreans (273 men, 384 women) aged 60 years or older who participated in the
Korean Social Life, Health, and Aging Project. Network size is a count of the
number of friends. Density of communication network is the number of connections
in the social network reported as a fraction of the total links possible in the
personal (ego-centric) network. Average frequency of communication (or meeting)
measures how often network members communicate (or meet) each other. The
association of each social network measure with BMI was investigated by multiple
linear regression analysis. RESULTS: After adjusting for potential confounders,
the men with lower density (<0.71) and higher network size (4-6) had the higher
BMI (beta=1.089, p=0.037) compared to the men with higher density (>0.83) and
lower size (1-2), but not in the women (p=0.393). The lowest tertile of
communication frequency was associated with higher BMI in the women (beta=0.885,
p=0.049), but not in the men (p=0.140). CONCLUSIONS: Our study suggests that
social network structure (network size and density) and activation (communication
frequency and meeting frequency) are associated with obesity among the elderly.
There may also be gender differences in this association.
PMID- 24349656
TI - Association of selected medical conditions with breast cancer risk in Korea.
AB - OBJECTIVES: To estimate the effect of medical conditions in the population of
Korea on breast cancer risk in a case-control study. METHODS: The cases were 3242
women with incident, histologically confirmed breast cancer in two major
hospitals interviewed between 2001 and 2007. The controls were 1818 women each
admitted to either of those two hospitals for a variety of non-neoplastic
conditions. Information on each disease was obtained from a standardized
questionnaire by trained personnel. Odds ratios (ORs) for each disease were
derived from multiple logistic regression adjusted for age, age of menarche,
pregnancy, age of first pregnancy, and family history of breast cancer. RESULTS:
Among all of the incident breast cancer patients, pre-existing diabetes (OR,
1.33; 95% confidence interval [CI], 0.99 to 1.78), hypertension (OR, 1.46; 95%
CI, 1.18 to 1.83), thyroid diseases (OR, 1.26; 95% CI, 1.00 to 1.58), and ovarian
diseases (OR, 1.70; 95% CI, 1.23 to 2.35) were associated with an increased risk
of breast cancer when other factors were adjusted for. In a stratified analysis
by menopausal status, pre-existing hypertension (pre-menopause OR, 0.80; 95% CI,
0.48 to 1.34 vs. post-menopause OR, 1.87; 95% CI, 1.44 to 2.43; p-heterogeneity
<0.01) and ovarian disease (pre-menopause OR, 4.20; 95% CI, 1.91 to 9.24 vs. post
menopause OR, 1.39; 95% CI, 1.02 to 1.91; p-heterogeneity 0.01) showed
significantly different risks of breast cancer. CONCLUSIONS: Our results suggest
the possibility that medical conditions such as hypertension affect breast cancer
development, and that this can differ by menopausal status. Our study also
indicates a possible correlation between ovarian diseases and breast cancer risk.
PMID- 24349657
TI - A trend analysis of the prevalence, awareness, treatment, and control of
hypertension by age group.
AB - OBJECTIVES: We examined the trends in prevalence, awareness, treatment, and
control of hypertension in Korea as a basis for improving hypertension control
programs. METHODS: 12 598 participants of the Korean National Health and
Nutrition Examination Survey were included in this study. Weighted linear
regression to test time trends from 2007 to 2011 was performed. RESULTS: The
prevalence of hypertension was 20.7% in 2007, 29.4% in 2009, and 26.2% in 2011.
Awareness of hypertension was 64.8% in 2007 and 61.1% in 2011. Awareness in those
aged 65 and over was greater than in younger groups (age 19 to 44 and 45 to 64;
p<0.001). The treatment rates were 58.4% in 2007 and 56.8% in 2011. The treatment
rate was greater for those 65 and over than for younger age groups (p<0.001). The
percentage of controlled hypertension was 37.6% in 2011. The percentage of
controlled hypertension in those 65 and over was higher than in younger age
groups (p<0.001). The treatment-control rates were 65.9% in 2007 and 67.7% in
2011. The prevalence of hypertension was higher in the males (p<0.001), while the
awareness (p<0.001), treatment (p<0.001), and control (p<0.001) rates were higher
in the females. CONCLUSIONS: The prevalence of hypertension was increasing and
the hypertension awareness, treatment, and control rates were low in younger age
groups and males.
PMID- 24349658
TI - Comparison of estimation algorithms in single-molecule localization.
AB - Different techniques have been advocated for estimating single molecule locations
from microscopy images. The question arises as to which technique produces the
most accurate results. Various factors, e.g. the stochastic nature of the photon
emission/detection process, extraneous additive noise, pixelation, etc., result
in the estimated single molecule location deviating from its true location. Here,
we review the results presented by [Abraham et. al, Optics Express, 2009, 23352
23373], where the performance of the maximum likelihood and nonlinear least
squares estimators for estimating single molecule locations are compared. Our
results show that on average both estimators recover the true single molecule
location in all scenarios. Comparing the standard deviations of the estimates, we
find that in the absence of noise and modeling inaccuracies, the maximum
likelihood estimator is more accurate than the non-linear least squares
estimator, and attains the best achievable accuracy for the sets of experimental
and imaging conditions tested. In the presence of noise and modeling
inaccuracies, the maximum likelihood estimator produces results with consistent
accuracy across various model mismatches and misspecifications. At high noise
levels, neither estimator has an accuracy advantage over the other. We also
present new results regarding the performance of the maximum likelihood estimator
with respect to the objective function used to fit data containing both additive
Gaussian and Poisson noise. Comparisons were also carried out between two
localization accuracy measures derived previously. User-friendly software
packages were developed for single molecule location estimation (EstimationTool)
and localization accuracy calculations (FandPLimitTool).
PMID- 24349660
TI - Full-Field versus Multifocal Electroretinography.
PMID- 24349659
TI - Extracellular membrane vesicles from umbilical cord blood-derived MSC protect
against ischemic acute kidney injury, a feature that is lost after inflammatory
conditioning.
AB - BACKGROUND: Mesenchymal stromal cells (MSC) are shown to have a great therapeutic
potential in many immunological disorders. Currently the therapeutic effect of
MSCs is considered to be mediated via paracrine interactions with immune cells.
Umbilical cord blood is an attractive but still less studied source of MSCs. We
investigated the production of extracellular membrane vesicles (MVs) from human
umbilical cord blood derived MSCs (hUCBMSC) in the presence (MVstim) or absence
(MVctrl) of inflammatory stimulus. METHODS: hUCBMSCs were cultured in serum free
media with or without IFN-gamma and MVs were collected from conditioned media by
ultracentrifugation. The protein content of MVs were analyzed by mass
spectrometry. Hypoxia induced acute kidney injury rat model was used to analyze
the in vivo therapeutic potential of MVs and T-cell proliferation and induction
of regulatory T cells were analyzed by co-culture assays. RESULTS: Both MVstim
and MVctrl showed similar T-cell modulation activity in vitro, but only MVctrls
were able to protect rat kidneys from reperfusion injury in vivo. To clarify this
difference in functionality we made a comparative mass spectrometric analysis of
the MV protein contents. The IFN-gamma stimulation induced dramatic changes in
the protein content of the MVs. Complement factors (C3, C4A, C5) and lipid
binding proteins (i.e apolipoproteins) were only found in the MVctrls, whereas
the MVstim contained tetraspanins (CD9, CD63, CD81) and more complete proteasome
complex accompanied with MHCI. We further discovered that differently produced MV
pools contained specific Rab proteins suggesting that same cells, depending on
external signals, produce vesicles originating from different intracellular
locations. CONCLUSIONS: We demonstrate by both in vitro and in vivo models
accompanied with a detailed analysis of molecular characteristics that
inflammatory conditioning of MSCs influence on the protein content and functional
properties of MVs revealing the complexity of the MSC paracrine regulation.
PMID- 24349661
TI - Multifocal electroretinography after high dose chloroquine therapy for malaria.
AB - PURPOSE: To investigate changes in multifocal electroretinography (mfERG)
parameters associated with high dose chloroquine therapy for treatment of malaria
in the Amazonia region of Brazil. METHODS: Forty-eight subjects who had received
chloroquine treatment for single or multiple malaria infections with a cumulative
dose ranging from 1,050 to 27,000mg were included. The control group consisted of
37 healthy aged-matched subjects. Data was collected on amplitude and implicit
time of the N1, P1 and N2 waves in the central macular hexagon (R1) and in five
concentric rings at different retinal eccentricities (R2-R6). RESULTS: No
significant difference was observed in any mfERG parameter between chloroquine
treated patients and control subjects. A comparison with previous data obtained
from patients with rheumatologic disorders in the same region of Brazil who had
received larger cumulative doses of chloroquine and had displayed mfERG changes,
indicated that retinal toxicity seems to be dependent on cumulative dose.
CONCLUSION: Lack of mfERG changes in the current study suggests that intensive
high dose chloroquine therapy for treatment of malaria is not associated with
retinal toxicity.
PMID- 24349662
TI - Pattern electroretinography in glaucoma suspects and early primary open angle
glaucoma.
AB - PURPOSE: To explore retinal ganglion cell (RGC) dysfunction in glaucoma suspects
and patients with early primary open angle glaucoma (POAG) using pattern
electroretinography (PERG). METHODS: Twenty glaucoma suspects (glaucomatous optic
disc appearance), 15 early POAG (based on abnormal discs and abnormal visual
fields) and 16 normal controls were enrolled. Transient PERG was recorded in
response to 0.8 degrees and 16 degrees black and white checkerboard stimuli.
Amplitude and peak time (latency) of the P50 and N95 components of the PERG
response, and the ratio of N95 amplitude in response to 0.8 degrees and 16
degrees checks were measured. RESULTS: N95 peak time (latency) was significantly
increased in both early manifest POAG and glaucoma suspects as compared to normal
controls (P<0.001). In early POAG, N95 amplitude in response to small (0.8
degrees ) checks and the small/large check ratio were reduced in comparison to
normal eyes (P<0.05). However, in glaucoma suspects no significant N95 amplitude
reduction was observed. No significant difference was observed among the study
groups in terms of P50 amplitude or peak time. CONCLUSION: The N95 PERG response
demonstrated uncoupled peak time and amplitude alterations in glaucoma. N95 peak
time was significantly increased both in glaucoma suspects and early POAG; N95
amplitude reduction was present only in early POAG. PERG may detect RGC
dysfunction (increased latency) before cell death (decreased amplitude) occurs.
PMID- 24349663
TI - Impression cytology in eyes with clinical and confocal scan features of
acanthamoeba keratitis.
AB - PURPOSE: To report impression cytology findings in specimens obtained from eyes
with clinical and confocal microscopic features of Acanthamoeba keratitis (AK).
METHODS: In this interventional case series, impression cytology was obtained
from corneas of patients with clinical and confocal microscopic features
indicative of AK. Specimens were stained with Periodic acid-Schiff/Papanicolaou
(PAS/PAP) and examined for the presence of PAS-reactive Acanthamoeba cysts and/or
hyperchromatic pear-shaped trophozoites. All specimens were then decolorized and
re-stained with calcofluor white (CFW) for the presence of chemofluorescent
cysts. RESULTS: Fifty-six eyes of 50 patients with mean age of 25.5+/-9.3 (range,
17 to 78) years were evaluated. Forty-one (82%) cases were female and 51 (91.1%)
eyes had history of contact lens wear. PAS-reactive Acanthamoeba cysts and/or
hyperchromatic pear-shaped trophozoites were identified in 53 eyes (94.6%), 2 of
which demonstrated only trophozoite- like structures. CFW staining was able to
reveal the presence of chemofluorescent cysts in all 51 specimens (91.1%) in
which cysts had been demonstrated with PAS/PAP staining. Trophozoites were not
detected with CFW due to background staining of the cellulose acetate strip used
for impression cytology. CONCLUSION: Corneal impression cytology, stained with
PAS/PAP or with CFW, successfully detects Acanthamoeba and can be employed for
early noninvasive diagnosis of AK.
PMID- 24349664
TI - Prevalence of keratoconus and subclinical keratoconus in subjects with
astigmatism using pentacam derived parameters.
AB - PURPOSE: To determine the prevalence of keratoconus (KCN) and subclinical KCN
among subjects with two or more diopters (D) of astigmatism, and to compare
Pentacam parameters among these subjects. METHODS: One hundred and twenty eight
eyes of 64 subjects with astigmatism >=2D were included in the study. All
subjects underwent a complete ophthalmic examination which included refraction,
visual acuity measurement, slit lamp biomicroscopy, retinoscopy, fundus
examination, conventional corneal topography and elevation-based topography with
Pentacam. The diagnosis of KCN and subclinical KCN was made by observing clinical
findings and topographic features; and confirmed by corneal thickness and
elevation maps of Pentacam. Several parameters acquired from Pentacam were
analyzed employing the Mann-Whitney U Test. RESULTS: Mean age of the study
population was 29.9+/-9.8 (range 15-45) years which included 39 (60.9%) female
and 25 (39.1%) male subjects. Maximum corneal power, index of vertical asymmetry,
keratoconus index and elevation values were significantly higher and pachymetry
was significantly thinner in eyes with clinical or subclinical KCN than normal
astigmatic eyes (P< 0.05). CONCLUSION: The current study showed that subjects
with 2D or more of astigmatism who present to outpatient clinics should undergo
corneal topography screening for early diagnosis of KCN even if visual acuity is
not affected. Pentacam may provide more accurate information about anterior and
posterior corneal anatomy especially in suspect eyes.
PMID- 24349665
TI - Axial length to corneal radius of curvature ratio and refractive errors.
AB - PURPOSE: To determine the distribution of axial length (AL) to corneal radius of
curvature (CRC) ratio and to evaluate its association with refractive errors in
an Iranian population. METHODS: In this cross sectional study, multistage cluster
sampling was used to select subjects 40-64 years of age residing in Shahroud,
northern Iran. All subjects underwent manifest and cycloplegic refraction, and
biometry using the Allegro Biograph (WaveLight AG, Erlangen, Germany).
Individuals with a history of intraocular surgery, extensive pterygia and ocular
trauma were excluded. RESULTS: Of a total of 6,311 patients, 5190 (82.2%)
participated in the study. We excluded 247 patients to adhere with study criteria
and 132 patients due to missing data. Mean AL/CRC was 3.034 [95% confidence
interval (CI), 3.031-3.037]. AL/CRC was 3.028 and 3.042 in female and male
subjects, respectively (P<0.001). The R2 coefficients between spherical
equivalent (SE) refractive error and AL/CRC, AL, CRC, lens thickness, and
anterior chamber depth were 0.607, 0.351, 0.012, 0.038, and 0.091, respectively.
Linear regression showed a 12.1 diopter (D) shift towards myopia with every 1
unit increase in AL/CRC (P<0.001). Mean AL/CRC was 3.472 among myopes with SE
less than-5.0D; this value decreased linearly and was as low as 2.690 among
hyperopes with SE more than 5.0D. R2 coefficients for AL/CRC with spherical and
cylindrical power were 0.560 and 0.071, respectively. CONCLUSIONS: Minimal
changes in AL/CRC lead to large changes in refractive error. The correlation
between refractive errors was significantly stronger with the AL/CRC ratio than
with AL and CRC alone.
PMID- 24349666
TI - Prevalence of refractive errors; the yazd eye study.
AB - PURPOSE: To determine the prevalence of refractive errors in Yazd, central Iran.
METHODS: This population-based study was performed in 2010-2011 and targeted
adults aged 40 to 80 years. Multi-stage random cluster sampling was applied to
select samples from urban and rural residents of Yazd. Manifest refraction,
visual acuity measurement, retinoscopy and funduscopy were performed for all
subjects. Myopia, hyperopia, astigmatism and anisometropia were defined as
spherical equivalent (SE) <-0.50 diopters (D), SE >+0.50 D, cylindrical error
>0.5 D and SE difference >=1 D between fellow eyes, respectively. RESULTS: From a
total of 2,320 selected individuals, 2,098 subjects (90.4%) participated out of
which 198 subjects were excluded due to previous eye surgery. The prevalence (95%
confidence interval) for myopia, hyperopia, astigmatism, anisometropia, -6 D
myopia or worse, and 4 D hyperopia or worse was 36.5% (33.6-39.4%), 20.6% (17.9
23.3%), 53.8% (51.3-56.3%), 11.9% (10.4-13.4%), 2.3% (1.6-2.9%) and 1.2% (0.6
1.8%), respectively. The prevalence of hyperopia, astigmatism and anisometropia
increased with age. The prevalence of myopia was significantly higher in female
subjects. The prevalence of with-the-rule, against-the-rule and oblique
astigmatism was 35.7%, 13.4% and 4.6%, respectively. The prevalence of against
the-rule astigmatism increased with age (P<0.001); with-the-rule astigmatism was
more common in women (P=0.038). CONCLUSION: More than half of the study
population had refractive errors; the prevalence of myopia and astigmatism was
higher than earlier studies in Iran. Since refractive errors are a major cause of
avoidable visual impairment, their high prevalence in this survey is important
from a public health perspective.
PMID- 24349667
TI - Rate of Post-traumatic Endophthalmitis with or without Injection of Balanced Salt
Solution.
AB - PURPOSE: In a study complementing a previous multicenter randomized clinical
trial on prophylactic injection of intraocular antibiotics during primary repair
of penetrating eye injuries (PEIs), we sought to determine whether needle
entrance and injection of balanced salt solution (BSS), per se, could increase
the rate of acute post-traumatic bacterial endophthalmitis (APBE). METHODS:
Patients randomized to the BSS injection arm (n=167) of the Traumatic
Endophthalmitis Trial, and eligible patients who had refused enrollment and
received no intraocular injections during primary repair (n=111) were compared
for the development of APBE. RESULTS: APBE occurred in 8 of 167 (4.8%) eyes in
the BSS group and in 5 of 111 (4.5%) eyes in the non-injection group (P=0.91).
Retained intraocular foreign bodies were present in 46 eyes including 25 (15%)
eyes in the BSS injection group and 21 (18.9%) eyes in the non-injection group
(P=0.38). Logistic regression analysis showed no significant difference between
BSS injected and non-injected eyes in terms of APBE (P=0.69). However, the
presence of intraocular foreign bodies was strongly associated with the risk of
endophthalmitis (P<0.001, OR=14.1, 95% CI: 4.1-48.5). CONCLUSION: Needle entrance
and intraocular injection of BSS during primary repair of PEIs does not increase
the risk of APBE.
PMID- 24349668
TI - The ubiquitin-proteasome system and microvascular complications of diabetes.
AB - The ubiquitin-proteasome system (UPS) is the mainstay of protein quality control
which regulates cell cycle, differentiation and various signal transduction
pathways in eukaryotic cells. The timely and selective degradation of surplus
and/or aberrant proteins by the UPS is essential for normal cellular physiology.
Any disturbance, delay or exaggeration in the process of selection,
sequestration, labeling for degradation and degradation of target proteins by the
UPS will compromise cellular and tissue homeostasis. High blood glucose or
hyperglycemia caused by diabetes disrupts normal vascular function in several
target organs including the retina and kidney resulting in the development of
diabetic retinopathy (DR) and diabetic nephropathy (DN). We and others have shown
that hyperglycemia and oxidative stress modulate UPS activity in the retina and
kidney. The majority of studies have focused on the kidney and provided insights
into the contribution of dysregulated UPS to microvascular damage in DN. The eye
is a unique organ in which a semi-fluid medium, the vitreous humor, separates the
neural retina and its anastomosed blood vessels from the semi-solid lens tissue.
The complexity of the cellular and molecular components of the eye may require a
normal functioning and well tuned UPS for healthy vision. Altered UPS activity
may contribute to the development of retinal microvascular complications of
diabetes. A better understanding of the molecular nature of the ocular UPS
function under normal and diabetic conditions is essential for development of
novel strategies targeting its activity. This review will discuss the association
of retinal vascular cell UPS activity with microvascular damage in DR with
emphasis on alterations of the PA28 subunits of the UPS.
PMID- 24349670
TI - Peripheral exudative hemorrhagic chorioretinopathy: a variant of polypoidal
choroidal vasculopathy?
AB - PURPOSE: To report a case of peripheral exudative hemorrhagic chorioretinopathy
(PEHCR) in an elderly patient. CASE REPORT: A 74-year-old Caucasian woman, with a
20-year history of a stable choroidal nevus in her right eye, was referred for
evaluation of two small hemorrhagic pigment epithelial detachments (PEDs)
affecting the temporal peripheral fundus of the same eye. Nine months later, the
lesions became larger and indocyanine green angiography revealed polypoidal
choroidal vascular changes corresponding to the location of the
ophthalmoscopically visible PEDs. Despite one session of verteporfin photodynamic
therapy, the lesions continued to enlarge eventually resulting in the development
of a large hemorrhagic PED, which failed to respond to two subsequent injections
of intravitreal bevacizumab. The final ophthalmoscopic appearance of the large
hemorrhagic PED was typical of PEHCR. CONCLUSION: This case suggests that
polypoidal choroidal vascular changes similar to that seen in our patient may
underlie the development of PEHCR in some cases.
PMID- 24349669
TI - Cerebrospinal fluid pressure and glaucoma.
AB - Eyes with normal-pressure glaucoma and those with high-pressure glaucoma can show
a similar optic nerve head appearance, while eyes with vascular optic
neuropathies show a markedly different optic disc appearance. Factors in addition
to intraocular pressure (IOP) may thus play a role in the pathogenesis of
glaucomatous optic neuropathy. Clinical and experimental studies showed that (1)
physiologic associations between cerebrospinal fluid (CSF) pressure, systemic
arterial blood pressure, IOP and body mass index exist; (2) a low CSF pressure
was associated with the development of glaucomatous optic nerve damage in cats;
(3) patients with normal (intraocular) pressure glaucoma had significantly lower
CSF pressure and a higher trans lamina cribrosa pressure difference when compared
to normal subjects; and (4) patients with normal- pressure glaucoma as compared
with patients with high-pressure glaucoma have a significantly narrower orbital
CSF space. A shallow orbital CSF space has been shown to be associated with a low
CSF pressure. Due to anatomic reasons, the orbital CSF pressure and the optic
nerve tissue pressure (and not the atmospheric pressure) form the retro-laminar
counter-pressure against the IOP and are thus part of the trans-lamina cribrosa
pressure difference and gradient. Assuming that an elevated trans-lamina cribrosa
pressure difference and a steeper trans-lamina cribrosa pressure gradient are
important for glaucomatous optic nerve damage, a low orbital CSF pressure would
therefore play a role in the pathogenesis of normal-(intraocular) pressure
glaucoma. Due to the association between CSF pressure and blood pressure, a low
blood pressure could be indirectly involved.
PMID- 24349671
TI - Retinitis Pigmentosa Associated with Vasoproliferative Tumors and Coats-like
Fundus.
AB - PURPOSE: To report two cases of retinitis pigmentosa (RP) associated with
vasoproliferative tumors (VPTs) and Coats-like fundus. CASE REPORTS: Two patients
with RP presented with recent loss of vision due to combined VPTs and Coats-like
retinal vascular alterations. One patient had two VPTs with adjacent capillary
nonperfusion, telangiectasia and aneurysmal vascular changes in one eye. The
other patient had prominent VPT with Coats-like retinal vascular alterations in
both eyes. These lesions received treatment resulting in improved vision in both
patients. CONCLUSION: Although rare, VPTs and Coats-like retinal vascular
alterations including retinal exudation associated with telangiectatic vessels,
aneurysmal changes and capillary nonperfusion may occur in patients with RP.
PMID- 24349672
TI - Hypotropic dissociated vertical deviation; a case report.
AB - PURPOSE: To report the clinical features of a rare case of hypotropic dissociated
vertical deviation (DVD). CASE REPORT: A 25-year-old female was referred with
unilateral esotropia, hypotropia and slow variable downward drift in her left
eye. She had history of esotropia since she had been 3-4 months of age. Best
corrected visual acuity was 20/20 in her right eye and 20/40 in the left one when
hyperopia was corrected. She underwent bimedial rectus muscle recession of 5.25mm
for 45 prism diopters (PDs) of esotropia. She was orthophoric 3 months after
surgery and no further operation was planned for correction of the hypotropic
DVD. CONCLUSION: This rare case of hypotropic DVD showed only mild amblyopia in
her non-fixating eye. The etiology was most probably acquired considering
hyperopia as a sign of early onset accommodative esotropia.
PMID- 24349673
TI - A case of primary congenital glaucoma.
PMID- 24349674
TI - Optical coherence tomography findings in a patient with myelinated retinal nerve
fiber layer.
PMID- 24349675
TI - Indications and techniques of endoscope assisted vitrectomy.
AB - The popularization of ophthalmic endoscopy has been promoted by recent
technological advancements that increase the number of indications for endoscopy.
These advancements have improved the endoscope's capabilities in its two
fundamental surgical advantages: (1) bypassing anterior segment opacities, and
(2) visualizing anteriorly positioned structures such as the ciliary bodies and
sub-iris space. In this article, the current state of the ophthalmic endoscope is
reviewed alongside its growing number of applications in glaucoma, vitreoretinal,
and ocular trauma surgery. We describe the role of endoscopy in
endocyclophotocoagulation for glaucoma, cyclitic membrane peeling in hypotony,
retinal detachment surgery, intraocular foreign body removal, severe
endophthalmitis, and pediatric traumatic vitreoretinal surgery. This review
examines both the pearls and limitations of the ophthalmic application of
endoscopy. In doing so, we hope to provide guidelines for using the endoscope and
also to highlight applications of endoscopy that merit further study.
PMID- 24349676
TI - Behcet's Disease: Autoimmune or Autoinflammatory?
PMID- 24349677
TI - Financial Distress in Cancer Patients.
AB - Novel diagnostic and therapeutic options offer hope to cancer patients with both
localized and advanced disease. However, many of these treatments are often
costly and even well-insured patients can face high out-of-pocket costs. Families
may also be at risk of financial distress due to lost wages and other treatment
related expenses. Research is needed to measure and characterize financial
distress in cancer patients and understand how it affects their quality of life.
In addition, health care providers need to be trained to counsel patients and
their families so they can make patient-centered treatment decisions that reflect
their preferences and values.
PMID- 24349678
TI - Prenatal exposure to phthalates is associated with decreased anogenital distance
and penile size in male newborns.
AB - Reproductive effects from phthalate exposure have been documented mostly in
animal studies. This study explored the association between prenatal exposure to
phthalate metabolites, anogenital distance and penile measurements in male
newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine
samples for phthalate analysis during their last prenatal visit, and the 73 who
gave birth to male infants were included in the study. The 73 male newborns were
weighed and measured using standardized methods after delivery. After adjusting
for creatinine and supine length at birth, significant inverse associations were
observed between an index of prenatal exposure to total phthalate exposure and
the distance from the anus to anterior base of the penis (beta = -0.191 mm per 1
MUg/l, P = 0.037), penile width (beta = -0.0414, P = 0.050) and stretched length
(beta = -0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate
exposure was associated with a reduction in the stretched length of the penis
(beta = -0.2604, P = 0.050). Human exposure to phthalates is a public health
concern, and the system most vulnerable to its potential effects seems to be the
immature male reproductive tract.
PMID- 24349679
TI - Post-traumatic stress in Crohn's disease and its association with disease
activity.
AB - OBJECTIVE: Violence, accidents and natural disasters are known to cause post
traumatic stress, which is typically accompanied by fear, suffering and impaired
quality of life. Similar to chronic diseases, such events preoccupy the patient
over longer periods. We hypothesised that post-traumatic stress could also be
caused by Crohn's disease (CD), and that CD specific post-traumatic stress could
be associated with an increased risk of disease exacerbation. METHODS: A cohort
of CD patients was observed over 18 months in various types of locations
providing gastroenterological treatment in Switzerland. The cohort included 597
consecutively recruited adults. At inclusion, CD specific post-traumatic stress
was assessed using the Post-traumatic Diagnostic Scale (range 0-51 points).
During follow-up, clinical aggravation was assessed by combining important
outcome measures. Patients with post-traumatic stress levels suggestive of a post
traumatic stress disorder (>= 15 points) were compared with patients with lower
post-traumatic stress levels as well as with patients without post-traumatic
stress. Also, the continuous relation between post-traumatic stress severity and
risk of disease exacerbation was assessed. RESULTS: The 88 (19.1%) patients
scoring >=15 points had 4.3 times higher odds of exacerbation (95% CI 2.6 to 7.2)
than the 372 (80.9%) patients scoring <15 points, and 13.0 times higher odds (95%
CI 3.6 to 46.2) than the 45 (9.8%) patients scoring 0 points. The odds of
exacerbation increased by 2.2 (95% CI 1.6 to 2.8) per standard deviation of post
traumatic stress. CONCLUSIONS: CD specific post-traumatic stress is frequent and
seems to be associated with exacerbation of CD. Thus gastroenterologists may want
to ask about symptoms of post-traumatic stress and, where relevant, offer
appropriate management according to current knowledge.
PMID- 24349680
TI - Synthesis of cyclobutane lignans via an organic single electron oxidant-electron
relay system.
AB - A direct method to synthesize lignan cyclobutanes and analogs via photoinduced
electron transfer is presented. A variety of oxygenated alkenes are employed to
furnish terminal or substituted cyclobutane adducts with complete regiocontrol,
yielding cycloadducts with trans stereochemistry. Key to minimizing competing
cycloreversion is the inclusion of an aromatic electron relay (ER). This method
has been adapted to the synthesis of the natural products magnosalin and
pellucidin A.
PMID- 24349681
TI - An introduction to the special issue on Multisensory Perception.
PMID- 24349682
TI - The roles of physical and physiological simultaneity in audiovisual multisensory
facilitation.
AB - A series of experiments measured the audiovisual stimulus onset asynchrony
(SOAAV), yielding facilitative multisensory integration. We evaluated (1) the
range of SOAAV over which facilitation occurred when unisensory stimuli were
weak; (2) whether the range of SOAAV producing facilitation supported the
hypothesis that physiological simultaneity of unisensory activity governs
multisensory facilitation; and (3) whether AV multisensory facilitation depended
on relative stimulus intensity. We compared response-time distributions to
unisensory auditory (A) and visual (V) stimuli with those to AV stimuli over a
wide range (300 and 20 ms increments) of SOAAV, across four conditions of varying
stimulus intensity. In condition 1, the intensity of unisensory stimuli was
adjusted such that d' ~ 2. In condition 2, V stimulus intensity was increased (d'
> 4), while A stimulus intensity was as in condition 1. In condition 3, A
stimulus intensity was increased (d' > 4) while V stimulus intensity was as in
condition 1. In condition 4, both A and V stimulus intensities were increased to
clearly suprathreshold levels (d' > 4). Across all conditions of stimulus
intensity, significant multisensory facilitation occurred exclusively for
simultaneously presented A and V stimuli. In addition, facilitation increased as
stimulus intensity increased, in disagreement with inverse effectiveness. These
results indicate that the requirements for facilitative multisensory integration
include both physical and physiological simultaneity.
PMID- 24349683
TI - Effect of visual stimuli on temporal order judgments of a sequence of pure tones.
AB - We investigated what effect visual spatial information had on auditory temporal
order judgments (TOJs) and examined what effect visual stimuli had on the TOJs of
sequences of pure tones in experiment 1. The auditory stimuli were sequences of
four distinct pure tones. The visual stimuli consisted of two vertically aligned
flashes: one flashed before the first tone and the other flashed after the last
tone. Participants judged whether the temporal order of the second and third
tones in auditory stimuli occurred with the higher tone being first or the lower
tone being first. As a result, the proportion of responses for higher-tone-first
increased when the flash of the upper LED preceded that of the lower LED,
independent of the actual temporal order. Participants in experiment 2 were asked
to make simultaneity judgments instead, which were also affected by visual
stimuli. The auditory stimuli in experiment 3 were the same as those in
experiment 1, whereas the visual stimuli consisted of two horizontally aligned
flashes. Furthermore, the participants made TOJs, which were not affected by the
horizontally aligned visual stimuli. We concluded that vertically aligned visual
stimuli had an effect on auditory TOJs with some response bias.
PMID- 24349684
TI - Early sound symbolism for vowel sounds.
AB - Children and adults consistently match some words (e.g., kiki) to jagged shapes
and other words (e.g., bouba) to rounded shapes, providing evidence for non
arbitrary sound-shape mapping. In this study, we investigated the influence of
vowels on sound-shape matching in toddlers, using four contrasting pairs of
nonsense words differing in vowel sound (/i/ as in feet vs. /o/ as in boat) and
four rounded-jagged shape pairs. Crucially, we used reduplicated syllables (e.g.,
kiki vs. koko) rather than confounding vowel sound with consonant context and
syllable variability (e.g., kiki vs. bouba). Toddlers consistently matched words
with /o/ to rounded shapes and words with /i/ to jagged shapes (p < 0.01). The
results suggest that there may be naturally biased correspondences between vowel
sound and shape.
PMID- 24349685
TI - Effects of retinal position on the visuo-motor adaptation of visual stability in
a virtual environment.
AB - Although the retinal image changes a great deal with the movement of our head or
eyes, we perceive a stable world (a phenomenon known as visual stability or
position constancy). Visual stability adaptively changes for each new combination
of vision and head motion, or to compensate for manipulated visuo-motor gain.
This study aims to investigate the effects of retinal positions on visuo-motor
adaptation and to discuss the neural mechanisms involved. I found that visuo
motor adaptation occurred, and was transferable from right to left visual fields
(Experiment 1), between the upper and lower visual fields (Experiment 2), and
between the central and peripheral visual fields (Experiment 4), and that for the
left visual field (Experiment 1) and the large visual field (Experiment 3) visuo
motor adaptations were effective. The dominance of the central vision was found
in Experiment 3 but not found in Experiment 4. These results suggest that the
visuo-motor adaptation of visual stability was not specific to the retinal
location, but is processed by a relatively high level of the perceptual system.
PMID- 24349686
TI - Effects of head movement and proprioceptive feedback in training of sound
localization.
AB - We investigated the effects of listeners' head movements and proprioceptive
feedback during sound localization practice on the subsequent accuracy of sound
localization performance. The effects were examined under both restricted and
unrestricted head movement conditions in the practice stage. In both cases, the
participants were divided into two groups: a feedback group performed a sound
localization drill with accurate proprioceptive feedback; a control group
conducted it without the feedback. Results showed that (1) sound localization
practice, while allowing for free head movement, led to improvement in sound
localization performance and decreased actual angular errors along the horizontal
plane, and that (2) proprioceptive feedback during practice decreased actual
angular errors in the vertical plane. Our findings suggest that unrestricted head
movement and proprioceptive feedback during sound localization training enhance
perceptual motor learning by enabling listeners to use variable auditory cues and
proprioceptive information.
PMID- 24349688
TI - Useful field of view in simulated driving: Reaction times and eye movements of
drivers.
AB - To examine the spatial distribution of a useful field of view (UFOV) in driving,
reaction times (RTs) and eye movements were measured in simulated driving. In the
experiment, a normal or mirror-reversed letter "E" was presented on driving
images with different eccentricities and directions from the current gaze
position. The results showed significantly slower RTs in the upper and upper left
directions than in the other directions. The RTs were significantly slower in the
left directions than in the right directions. These results suggest that the UFOV
in driving may be asymmetrical among the meridians in the visual field.
PMID- 24349689
TI - SFS? Not likely....
AB - SFS (Shape From Shading) theory is based upon the Lambertian paradigm. Our visual
demonstrations imply that this paradigm fails to apply to the conventional
stimuli used to probe vision.
PMID- 24349687
TI - Uni- and multisensory brain areas are synchronised across spectators when
watching unedited dance recordings.
AB - The superior temporal sulcus (STS) and gyrus (STG) are commonly identified to be
functionally relevant for multisensory integration of audiovisual (AV) stimuli.
However, most neuroimaging studies on AV integration used stimuli of short
duration in explicit evaluative tasks. Importantly though, many of our AV
experiences are of a long duration and ambiguous. It is unclear if the enhanced
activity in audio, visual, and AV brain areas would also be synchronised over
time across subjects when they are exposed to such multisensory stimuli. We used
intersubject correlation to investigate which brain areas are synchronised across
novices for uni- and multisensory versions of a 6-min 26-s recording of an
unfamiliar, unedited Indian dance recording (Bharatanatyam). In Bharatanatyam,
music and dance are choreographed together in a highly intermodal-dependent
manner. Activity in the middle and posterior STG was significantly correlated
between subjects and showed also significant enhancement for AV integration when
the functional magnetic resonance signals were contrasted against each other
using a general linear model conjunction analysis. These results extend previous
studies by showing an intermediate step of synchronisation for novices: while
there was a consensus across subjects' brain activity in areas relevant for
unisensory processing and AV integration of related audio and visual stimuli, we
found no evidence for synchronisation of higher level cognitive processes,
suggesting these were idiosyncratic.
PMID- 24349690
TI - Adaptation effects to attractiveness of face photographs and art portraits are
domain-specific.
AB - We studied the neural coding of facial attractiveness by investigating effects of
adaptation to attractive and unattractive human faces on the perceived
attractiveness of veridical human face pictures (Experiment 1) and art portraits
(Experiment 2). Experiment 1 revealed a clear pattern of contrastive
aftereffects. Relative to a pre-adaptation baseline, the perceived attractiveness
of faces was increased after adaptation to unattractive faces, and was decreased
after adaptation to attractive faces. Experiment 2 revealed similar aftereffects
when art portraits rather than face photographs were used as adaptors and test
stimuli, suggesting that effects of adaptation to attractiveness are not
restricted to facial photographs. Additionally, we found similar aftereffects in
art portraits for beauty, another aesthetic feature that, unlike attractiveness,
relates to the properties of the image (rather than to the face displayed).
Importantly, Experiment 3 showed that aftereffects were abolished when adaptors
were art portraits and face photographs were test stimuli. These results suggest
that adaptation to facial attractiveness elicits aftereffects in the perception
of subsequently presented faces, for both face photographs and art portraits, and
that these effects do not cross image domains.
PMID- 24349691
TI - Perceptual organization in colour perception: Inverting the gamut expansion
effect.
AB - In the well-known gamut expansion effect, uniformly coloured target patches are
perceived as more colourful when they are embedded in a uniform grey surround
than when they are embedded in a variegated one. Here, we provide a demonstration
showing that this effect can be inverted when the uniformly coloured target
patches are replaced by variegated ones. This observation suggests that the gamut
expansion effect is due to mechanisms of transparency perception rather than due
to contrast adaptation.
PMID- 24349692
TI - Displaying optic flow to simulate locomotion: Comparing heading and steering.
AB - Optic flow can be used by humans to determine their direction of heading as well
as controlling steering. Dot-flow displays have been widely used to investigate
these abilities but it is unclear whether photorealistic textures would provide
better information for controlling high-speed steering. Here, we examine the
accuracy of heading judgements from dot-flow displays of different densities and
luminance and then compare to a scene containing a textured ground. We then
examine steering behaviour using these same displays to determine whether
accurate heading conditions necessarily equate to successful steering. Our
findings suggest that the bright dense dot-flow displays led to equivalent
performance as the ground texture when judging heading, and this was also true
when steering. The intermediate dot-flow conditions (with fewer and faded dots)
revealed that some conditions that led to accurate heading judgements were
insufficient for accurate steering. It seems, therefore, that heading perception
should not be considered synonymous with successful steering control, and
displays that support one ability will not necessarily support the other.
PMID- 24349693
TI - Helmholtz illusion makes you look fit only when you are already fit, but not for
everyone.
AB - A square filled with horizontal stripes is perceived as thinner than one with
vertical stripes (Helmholtz illusion). This is not consistent with a common
belief that horizontally striped clothing makes a person look fatter, and studies
on this problem have shown inconsistent results. Here, we demonstrate three
factors that could have complicated the issue. First, the Helmholtz effect is
stronger for a thin figure than for a fat one, with possible reversal for the
latter. Second, we found large variability across participants, suggesting
dependence on features to attend. Third, there was strong hysteresis as to the
order of testing fat and thin figures, suggesting the effect of surrounding
people in daily life. There can be yet other factors, but we should note that
this apparently simple case of application of a geometrical illusion in daily
perception should be taken as a rather complex phenomenon.
PMID- 24349695
TI - The small step toward asymmetry: Aesthetic judgment of broken symmetries.
AB - Symmetry and complexity both affect the aesthetic judgment of abstract patterns.
However, although beauty tends to be associated with symmetry, there are
indications that small asymmetries can also be beautiful. We investigated the
influence of small deviations from symmetry on people's aesthetic liking for
abstract patterns. Breaking symmetry not only decreased patterns' symmetry but
also increased their complexity. While an increase of complexity normally results
in a higher liking, we found that even a small decrease of symmetry has a strong
effect, such that patterns with slightly broken symmetries were significantly
less liked than fully symmetric ones.
PMID- 24349694
TI - Spatial location in brief, free-viewing face encoding modulates contextual face
recognition.
AB - The effect of the spatial location of faces in the visual field during brief,
free-viewing encoding in subsequent face recognition is not known. This study
addressed this question by tagging three groups of faces with cheating,
cooperating or neutral behaviours and presenting them for encoding in two visual
hemifields (upper vs. lower or left vs. right). Participants then had to indicate
if a centrally presented face had been seen before or not. Head and eye movements
were free in all phases. Findings showed that the overall recognition of
cooperators was significantly better than cheaters, and it was better for faces
encoded in the upper hemifield than in the lower hemifield, both in terms of a
higher d' and faster reaction time (RT). The d' for any given behaviour in the
left and right hemifields was similar. The RT in the left hemifield did not vary
with tagged behaviour, whereas the RT in the right hemifield was longer for
cheaters than for cooperators. The results showed that memory biases in
contextual face recognition were modulated by the spatial location of briefly
encoded faces and are discussed in terms of scanning reading habits, top-left
bias in lighting preference and peripersonal space.
PMID- 24349696
TI - Fast lemons and sour boulders: Testing crossmodal correspondences using an
internet-based testing methodology.
AB - According to a popular family of hypotheses, crossmodal matches between distinct
features hold because they correspond to the same polarity on several conceptual
dimensions (such as active-passive, good-bad, etc.) that can be identified using
the semantic differential technique. The main problem here resides in turning
this hypothesis into testable empirical predictions. In the present study, we
outline a series of plausible consequences of the hypothesis and test a variety
of well-established and previously untested crossmodal correspondences by means
of a novel internet-based testing methodology. The results highlight that the
semantic hypothesis cannot easily explain differences in the prevalence of
crossmodal associations built on the same semantic pattern (fast lemons, slow
prunes, sour boulders, heavy red); furthermore, the semantic hypothesis only
minimally predicts what happens when the semantic dimensions and polarities that
are supposed to drive such crossmodal associations are made more salient (e.g.,
by adding emotional cues that ought to make the good/bad dimension more salient);
finally, the semantic hypothesis does not explain why reliable matches are no
longer observed once intramodal dimensions with congruent connotations are
presented (e.g., visually presented shapes and colour do not appear to
correspond).
PMID- 24349697
TI - The artist's advantage: Better integration of object information across eye
movements.
AB - Over their careers, figurative artists spend thousands of hours analyzing objects
and scene layout. We examined what impact this extensive training has on the
ability to encode complex scenes, comparing participants with a wide range of
training and drawing skills on a possible versus impossible objects task. We used
a gaze-contingent display to control the amount of information the participants
could sample on each fixation either from central or peripheral visual field.
Test objects were displayed and participants reported, as quickly as possible,
whether the object was structurally possible or not. Our results show that when
viewing the image through a small central window, performance improved with the
years of training, and to a lesser extent with the level of skill. This suggests
that the extensive training itself confers an advantage for integrating object
structure into more robust object descriptions.
PMID- 24349698
TI - Comparing sensitivity to facial asymmetry and facial identity.
AB - Bilateral symmetry is a facial feature that plays an important role in the
aesthetic judgments of faces. The extent to which symmetry contributes to the
identification of faces is less clear. We investigated the relationship between
facial asymmetry and identity using synthetic face stimuli where the geometric
identity of the face can be precisely controlled. Thresholds for all observers
were 2 times lower for discriminating facial asymmetry than they were for
discriminating facial identity. The advantage for discriminating asymmetrical
forms was not observed using nonface shape stimuli, suggesting this advantage is
face-specific. Moreover, asymmetry thresholds were not affected when faces were
either inverted or constructed about a nonmean face. These results, taken
together, suggest that facial asymmetry is a characteristic that we are
exquisitely sensitive to, and that may not contribute to face identification.
This conclusion is consistent with neuroimaging evidence that suggests that face
symmetry and face identity are processed by different neural mechanisms.
PMID- 24349699
TI - Image regions contributing to perceptual translucency: A psychophysical reverse
correlation study.
AB - The spatial luminance relationship between shading patterns and specular
highlight is suggested to be a cue for perceptual translucency (Motoyoshi, 2010).
Although local image features are also important for translucency perception
(Fleming & Bulthoff, 2005), they have rarely been investigated. Here, we aimed to
extract spatial regions related to translucency perception from computer graphics
(CG) images of objects using a psychophysical reverse-correlation method. From
many trials in which the observer compared the perceptual translucency of two CG
images, we obtained translucency-related patterns showing which image regions
were related to perceptual translucency judgments. An analysis of the luminance
statistics calculated within these image regions showed that (1) the global rms
contrast within an entire CG image was not related to perceptual translucency and
(2) the local mean luminance of specific image regions within the CG images
correlated well with perceptual translucency. However, the image regions
contributing to perceptual translucency differed greatly between observers. These
results suggest that perceptual translucency does not rely on global luminance
statistics such as global rms contrast, but rather depends on local image
features within specific image regions. There may be some "hot spots" effective
for perceptual translucency, although which of many hot spots are used in judging
translucency may be observer dependent.
PMID- 24349700
TI - Shapes displayed with durations in the microsecond range do not obey Bloch's law
of temporal summation.
AB - Shape patterns were displayed with simultaneous brief flashes from a light
emitting diode array. Flash durations in the microsecond range and luminous
intensities were adjusted to vary the degree of successful shape recognition.
Four experiments were conducted to test whether Bloch's law would apply in this
task. Bloch's law holds that for very brief flashes the perceptual threshold is
determined by the total number of photons being delivered, i.e., there is
reciprocity of intensity and duration. The present results did not find that
effectiveness of flashes was based on the total quantity of photons, as predicted
by Bloch's law. Additionally, the evidence points to a visual mechanism that has
ultra-high temporal precision that either registers the rate of photon flux or
the duration of flashes.
PMID- 24349701
TI - Depth effect on lightness revisited: The role of articulation, proximity and
fields of illumination.
AB - The coplanar ratio principle proposes that when the luminance range in an image
is larger than the canonical reflectance range of 30:1, the lightness of a target
surface depends on the luminance ratio between that target and its adjacent
coplanar neighbor (Gilchrist, 1980). This conclusion is based on experiments in
which changes in the perceived target depth produced large changes in its
perceived lightness without significantly altering the observers' retinal image.
Using the same paradigm, we explored how this depth effect on lightness depends
on display complexity (articulation), proximity of the target to its highest
coplanar luminance and spatial distribution of fields of illumination.
Importantly, our experiments allowed us to test differing predictions made by the
anchoring theory (Gilchrist et al., 1999), the coplanar ratio principle, as well
as other models. We report three main findings, generally consistent with
anchoring theory predictions: (1) Articulation can substantially increase the
depth effect. (2) Target lightness depends not on the adjacent luminance but on
the highest coplanar luminance, irrespective of its position relative to the
target. (3) When a plane contains multiple fields of illumination, target
lightness depends on the highest luminance in its field of illumination, not on
the highest coplanar luminance.
PMID- 24349703
TI - Golden perception: Simulating perceptual habits of the past.
AB - Medieval times were neither dark nor grey; natural light illuminated colourful
scenes depicted in paintings through coloured windows and via artificial beeswax
candlelight. When we enter, for example, a church to inspect its historic
treasures ranging from mosaics to depictions of saints, we do this under quite
unfavourable conditions; particularly as we mainly depend on artificial halogen,
LED or fluorescent light for illuminating the desired object. As these light
spectrums are different from the natural light conditions under which the old
masterpieces were previously developed and perceived, the perceptual effects may
dramatically differ, leading to significantly altered affective and cognitive
processing. Different qualities of processing might particularly be triggered
when perceiving artworks which deal with specific material prone to strong
interaction with idiosyncratic light conditions, for instance gold-leafed
surfaces that literally start to glow when lit by candles. We tested the
perceptual experiences of a figurative piece of art which we created in 3
(foreground) by 3 (background) versions, illuminated under three different light
conditions (daylight, coloured light and beeswax candlelight). Results
demonstrated very different perceptual experiences with stunning effects for the
interaction of the specific painting depicted on a gold-leafed background lit by
candlelight.
PMID- 24349702
TI - Apparent sharpness of 3D video when one eye's view is more blurry.
AB - When the images presented to each eye differ in sharpness, the fused percept
remains relatively sharp. Here, we measure this effect by showing stereoscopic
videos that have been blurred for one eye, or both eyes, and psychophysically
determining when they appear equally sharp. For a range of blur magnitudes, the
fused percept always appeared significantly sharper than the blurrier view. From
these data, we investigate to what extent discarding high spatial frequencies
from just one eye's view reduces the bandwidth necessary to transmit perceptually
sharp 3D content. We conclude that relatively high-resolution video transmission
has the most potential benefit from this method.
PMID- 24349704
TI - Biochemical and biological characterization of Naja kaouthia venom from North
East India and its neutralization by polyvalent antivenom.
AB - This study describes biochemical and biological properties of Naja kaouthia
(Indian monocled cobra) venom of North-East India. The LD50 of the crude venom
was found to be 0.148mg/kg and neurotoxicitic symptoms like paralysis of lower
limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed.
The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed
weak proteolytic and low direct hemolytic activities. It did not exhibit any
hemorrhage when injected intradermally to mice. Anticoagulant activity was
prominent when recalcification, prothrombin and activated partial thrombinplastin
time were tested on platelet poor plasma. Rotem analysis of whole citrated blood
in presence of venom showed delay in coagulation time and clot formation time.
Fibrinogen of whole citrated blood was depleted by venom when analyzed in
Sonoclot. Crude venom at 10ug and after 16hr of incubation was found to degrade
alpha chain of fibrinogen. Neutralization study showed that Indian polyvalent
antivenom could neutralize some of the biochemical and biological activities as
well as its fibrinogenolytic activity.
PMID- 24349705
TI - Anti-thrombogenic properties of a nitric oxide-releasing dextran derivative:
evaluation of platelet activation and whole blood clotting kinetics.
AB - Controlling platelet activation and clotting initiated by cardiovascular
interventions remains a major challenge in clinical practice. In this work, the
anti-thrombotic properties of a polysaccharide-based nitric oxide (NO)-releasing
dextran derivative are presented. Total platelet adhesion, platelet morphology
and whole blood clotting kinetics were used as indicators to evaluate the anti
clotting properties of this material. With a total NO delivery of 0.203+/-0.003
MUmol, the NO-releasing dextran derivative (Dex-SNO) mixed with blood plasma
demonstrated a significantly lower amount of platelet adhesion and activation
onto a surface and reduced whole blood clotting kinetics. Nearly 75% reduction in
platelet adhesion and a significant retention of platelet morphology were
observed with blood plasma treated with Dex-SNO, suggesting this to be a
potential anti-platelet therapeutic agent for preventing thrombosis that does not
have an adverse effect on circulating platelets.
PMID- 24349706
TI - Microfluidic Assembly of Cationic-beta-Cyclodextrin:Hyaluronic Acid-Adamantane
Host:Guest pDNA Nanoparticles.
AB - Traditionally, transfection complexes are typically formed by bulk mixing,
producing particles with high polydispersity and limited control over vector
size. Herein, we demonstrate the use of a commercial micro-reactor to assemble
pDNA:cationic cyclodextrin:pendant polymer nanoparticles using a layer-by-layer
approach. Our studies reveal that the particles formulated via microfluidic
assembly have much smaller sizes, lower polydispersity, lower zeta-potentials,
and comparable cell viability and transfection profiles in HeLa cells than bulk
mixed particles. The complexes also show a flow rate-dependent stability, with
particles formed at slower flow rates giving rise to more stable complexes as
determined by heparin challenge. Our findings suggest that microfluidic reactors
offer an attractive method for assembling reproducible, size-controlled complexes
from multi-component transfection complex assemblies.
PMID- 24349707
TI - Collagen-Based Substrates with Tunable Strength for Soft Tissue Engineering.
AB - Through the use of mechanical reinforcement of collagen matrices, mechanically
strong and compliant 3D tissue mimetic scaffolds can be generated that act as
scaffolds for soft tissue engineering. Collagen has been widely used for the
development of materials for repair, augmentation or replacement of damaged or
diseased tissue. Herein we describe a facile method for the layer-by-layer
fabrication of robust planar collagen fiber constructs. Collagen gels cast in a
phosphate buffer were dried to form dense collagen mats. Subsequent gels were
layered and dried atop mats to create multilayer constructs possessing a range of
tunable strengths (0.5 - 11 MPa) and stiffness (1 - 115 MPa). Depending on
processing conditions and crosslinking of constructs, strain to failure ranged
between 9 to 48%. Collagen mats were constructed into hernia patches that
prevented hernia recurrence in Wistar rats.
PMID- 24349709
TI - Primary hepatic leiomyosarcoma in a 5-month-old female infant.
AB - Leiomyosarcoma is a malignant mesenchymal neoplasm deriving from the smooth
muscle cells. Primary hepatic leiomyosarcoma is very rare. Its onset is always
during middle and old age. Herein, we present a case of primary hepatic
leiomyosarcoma in a 5-month-old girl who may be the youngest patient reported in
the known published English literature.
PMID- 24349708
TI - Orbital phlebography in idiopathic intracranial hypertension and chronic tension
type headache.
AB - BACKGROUND: Pathologic signs in orbital phlebographies have been reported in
various neurological diseases. PURPOSE: To study if pathologic signs in orbital
phlebography may be markers of inflammation primarily affecting intracranial
capillaries, which would cause intracranial hypertension. MATERIAL AND METHODS:
Two groups with different intracranial cerebrospinal fluid pressures (Pcsf) were
compared as to inflammatory markers in serum and pathologic signs in orbital
phlebographies. Nine consecutive patients with idiopathic intracranial
hypertension (IIH) with bilateral papilledema and eight consecutive patients with
chronic tension-type headache (CTTH) were investigated prospectively with
fibrinogen, orosomucoid, haptoglobin in serum, and invasive orbital phlebograms.
The angiograms were evaluated by two skilled neuroradiologists, independent of
each other and without knowledge of the diagnoses or aim of the study, as to the
following pathologic signs: (i) narrowing of superior ophthalmic veins; (ii)
caliber changes of intraorbital veins; (iii) collaterals of intraorbital veins;
(iv) flow to cavernous sinus; and (v) asymmetric drainage of cavernous sinus.
RESULTS: Mean body mass index was >30 kg/m(2) in both groups. Pcsf was >200 < 250
mm H2O in 50% of the CTTH and >350 mm H2O in all IIH patients. No difference in
inflammatory markers in blood was found. The phlebographies of the IIH patients
had more pathologic signs and were considered pathologic significantly more often
than the ones of the CTTH patients (P < 0.001). CONCLUSION: The difference as to
phlebographic pathologic signs between the IIH and the CTTH patients with
different Pcsf supports the hypothesis that such phlebographic signs are markers
of inflammation primarily affecting intracranial capillaries, which would disturb
cerebrospinal fluid regulation causing intracranial hypertension.
PMID- 24349710
TI - A case of pneumoperitoneum and retropneumoperitoneum without bowel perforation
due to extensive intestinal necrosis as a complication to chemotherapy: CT
evaluation.
AB - Acute intestinal ischemia continues to be a challenging diagnostic problem with
high mortality. We describe a rare case of acute intestinal necrosis, due to
vasculitis, related with chemotherapy. A patient was examined in our emergency
department, presenting with abdominal pain. Three months before he had undergone
an operation for lung carcinoma (lobectomy) and received chemotherapy. CT of the
abdomen demonstrated free air in 10 different locations: hepatic part of the
portal vein, branches of mesenteric veins, femoral and iliac veins, the bowel
wall, peritoneal cavity and retroperitoneal space, abdominal muscles, inguinal
canals, meso-sigmoid space, and in the para-rectal space. Moreover, pathological
findings revealed that the free air in the peritoneum and retropneumoperitoneum
occurred without intestinal perforation, but with transudation through the
necrotic bowel wall. This is a rare complication of chemotherapy. This case
refers to the unusual CT findings which appeared in this patient. The key to a
better outcome is early diagnosis of this condition and the CT examination of the
abdomen plays an important role.
PMID- 24349711
TI - Wandering spleen with gastric volvulus and intestinal non-rotation in an adult
male patient.
AB - We report an extremely rare case of wandering spleen (WS) complicated with
gastric volvulus and intestinal non-rotation in a male adult. A 22-year-old man
who had been previously treated for Wilson disease was admitted with severe
abdominal pain. Radiological findings showed WS in the midline of the pelvic
area. The stomach was mesenteroaxially twisted and intestinal non-rotation was
observed. Radiology results did not show any evidence of splenic or
gastrointestinal (GI) infarction. Elective emergency laparoscopy confirmed WS and
intestinal non-rotation; however, gastric volvulus was not observed. It was
suspected that the stomach had untwisted when gastric and laparoscopic tubes were
inserted. Surgery is strongly recommended for WS because of the high risk of
serious complications; however, some asymptomatic adult patients are still
treated conservatively, such as the patient in this study. The present case is
reported with reference to the literature.
PMID- 24349712
TI - Computed tomographic findings of radiation-induced acute adrenal injury with
associated radiation nephropathy: a case report.
AB - Radiation nephropathy was first recognized in 1906. The kidney is a
radiosensitive organ with a tolerance dose (5% complications in 5 years) of 20
Gray. The imaging findings of acute and chronic radiation induced renal injury
are previously described. Radiation-induced adrenal injury, to our knowledge, has
not been described in the literature. Unlike the kidneys and other upper
abdominal organs, the adrenal glands are traditionally thought to be radio
resistant, protected from radiation-induced injury by proximity to adjacent
organs and by the adrenal medulla which reportedly has increased radio
resistance. We present the computed tomographic imaging findings of a patient
with acute radiation induced adrenal injury which resulted in adrenal
insufficiency following radiotherapy of an adjacent thecal metastasis.
PMID- 24349713
TI - Caseous calcification of the mitral annulus on MDCT: a rare intracardiac mass.
AB - Caseous calcification of the mitral annulus is a rare form of chronic
degenerative process in the mitral valve fibrous ring with a mass-like appearance
that has to be in the differential of the radiologist and cardiologist. We
present the case of an 82-year-old woman in whom a tumor-like calcified mass in
the posterior side of the mitral valve annulus was detected at echocardiography,
and the diagnosis of caseous calcification was confirmed on multidetector
computed tomography (MDCT). The diagnostic features of this rare cardiac mass are
described.
PMID- 24349714
TI - Transcatheter arterial embolization of anomalous systemic arterial supply to the
basal segment of the lung.
AB - We describe the case of a 67-year-old woman with an anomalous systemic arterial
supply to the basal segment of the lung, which was managed successfully by
transcatheter arterial embolization (TAE) with microcoils. Her chest computed
tomography (CT) scan showed diffuse ground-glass opacity in the left lower lobe,
no bronchial abnormalities, and blood supply from an anomalous artery originating
from the descending thoracic aorta, with drainage to the normal pulmonary vein.
We successfully performed TAE under balloon occlusion of the anomalous artery,
without complications. TAE is a minimally invasive, safe, and valuable method,
and could be used as first-line treatment in such cases.
PMID- 24349715
TI - Phantom-based quality assurance measurements in B-mode ultrasound.
AB - BACKGROUND: Recommended phantom-based quality assurance measurements in B-mode
ultrasound (US) may be tedious. For the purpose of cost-effective US quality
assurance it is important to evaluate measurements that effectively reflect the
quality of US scanner. PURPOSE: To find out which recommended phantom-based
quality assurance measurements are effective in detecting dead or weak transducer
elements or channels in US scanners when visual image analysis and manual
measurements are used. MATERIAL AND METHODS: Altogether 66 transducers from 33 US
scanners were measured using a general purpose phantom and a transducer tester.
The measurements were divided into two groups. Group I consisted of phantom-based
uniformity measurement, imaging the air with a clean transducer (air image) and
measuring the transducer with the transducer tester, and group II of phantom
based measurements of depth of penetration, beam profile, near field, axial and
lateral resolution, and vertical and horizontal distance accuracy. The group II
measurements were compared to group I measurements. RESULTS: With group I
measurements, the results with 20% of the transducers were found defective. With
35% of the transducers the results were considered defective in group II
measurements. Concurrent flaws in both groups were found with 11% of the
transducers. CONCLUSION: Phantom-based measurements of depth of penetration, beam
profile, near field, axial and lateral resolution, and vertical and horizontal
distance accuracy did not consistently detect dead or weak transducer elements or
channels in US scanners.
PMID- 24349716
TI - Diagnostic value of apparent diffusion coefficient for the accurate assessment
and differentiation of intracranial meningiomas.
AB - BACKGROUND: Diffusion-weighted imaging (DWI) along with the calculation of
apparent diffusion coefficient (ADC), is a novel, non-invasive, and reliable
technique of choice for accurate assessment and for the treatment planning of
different types of brain tumors. It is more advantageous in the distinction and
differentiation of benign from malignant meningiomas on the basis of ADC values.
PURPOSE: To investigate the utility of DW magnetic resonance imaging (MRI), and
to compare the apparent diffusion coefficient (ADC) obtained at two b-values for
an authentic and preoperative characterization of meningiomas. MATERIAL AND
METHODS: Twenty-six patients with clinically diagnosed or histologically verified
meningioma (18 benign and 8 malignant) underwent imaging including DWI at 1.5 T.
DW images were obtained at b = 1000 s/mm(2) and b = 2000 s/mm(2), ADC maps were
generated at both the b-values. Signal intensities (SIs) and ADCs for solid
tumorous tissues, contralateral normal tissues, and peritumoral edema were
calculated and normalized ADC (NADC) ratio were determined for tumorous tissues.
SI scores, ADC maps, and ADC values were analyzed visually and quantitatively,
and were compared at both the b-values. RESULTS: DW images at b = 2000 s/mm(2)
were more conspicuity (either hyperintense or hypointense) with improved
contrast. The mean ADC of malignant meningiomas (0.64 +/- 0.05 and 0.42 +/- 0.03)
was significantly lower (P < 0.05) as compared with benign meningiomas (1.04 +/-
0.12 and 0.80 +/- 0.07) at both the b-values. Mean NADC ratio in the malignant
type was also significantly lower (P < 0.05) than the benign type at both the b
values. Mean ADC values for peritumoral edema do not differ between benign and
malignant meningiomas. CONCLUSION: 1.5-T DWI using high b-values improved our
ability to differentiate benign from malignant meningiomas. DWI may play an
important role in the preoperative radiological evaluation and the recognition of
these types for proper surgical treatment.
PMID- 24349717
TI - Imaging findings for malignancy-mimicking nodular fasciitis of the breast and a
review of previous imaging studies.
AB - We report a case of nodular fasciitis of the breast mimicking malignant tumor. A
41-year-old female patient with a palpable mass in the upper center of the left
breast present for 1 week visited our hospital. A mammogram showed an oval
isodense with a partially indistinct margin. Ultrasonography demonstrated a
hypoechoic mass, 8 * 11 mm in size. Breast cancer could not be excluded based on
mammographic and ultrasonographic (US) findings. A core needle biopsy and
excisional biopsy were performed. Histopathologic examination revealed a
diagnosis of nodular fasciitis of the breast. The mammographic and US findings of
nodular fasciitis in the breast is reviewed.
PMID- 24349718
TI - The Decomposed Affiliation Exposure Model: A Network Approach to Segregating Peer
Influences from Crowds and Organized Sports.
AB - Self-identification with peer crowds (jocks, popular kids, druggies, etc.) has an
important influence on adolescent substance use behavior. However, little is
known about the impact of the shared nature of crowd identification on different
stages of adolescent drinking behavior, or the way crowd identification interacts
with participation in school-sponsored sports activities. This study examines
drinking influences from (1) peers with shared crowd identities, and (2) peers
who jointly participate in organized sports at their school (activity members).
This study introduces a new network analytic approach that can disentangle the
effects of crowd identification and sports participation on individual behavior.
Using survey data from adolescents in five high schools in a predominantly a
Hispanic/Latino district (N=1,707), this article examines the association between
social influences and each stage of drinking behavior (intention to drink,
lifetime, past-month, and binge drinking) by conducting an ordinal regression
analysis. The results show that both shared identities and joint participation
were associated with all stages of drinking, controlling for friends' influence.
Additionally, shared identification overlapped with joint participation was
associated with more frequent drinking. Related policy implications are
discussed.
PMID- 24349719
TI - Hemocompatibility of Chitosan/poly(acrylic acid) Grafted Polyurethane Tubing.
AB - The activation and adhesion of platelets or whole blood exposed to chitosan (CH)
grafted surfaces is used to evaluate the hemocompatibility of biomaterials. The
biomaterial surfaces are polyurethane (PU) tubes grafted with an inner
poly(acrylic acid) (PAA) and an outer CH or quaternary ammonium modified CH (CH
Q) brush. The CH, CH-Q and PAA grafted layers were characterized by ellipsometry
and fluorescence microscopy. Material wear tests demonstrate that CH (CH-Q) is
stably grafted onto PU tubes upon exposure to saline solution for 7 days. Using
quartz-crystal microbalances with dissipation (QCM-D), in-situ adsorption of
blood plasma proteins on CH and CH-Q compared to a silicon oxide control was
measured. The QCM-D results showed that the physically adsorbed plasma protein
layer on CH-Q and CH surfaces is softer and more viscous than the protein layer
on the SiO2 surface. The CH-Q layer thus has the weakest interaction with plasma
proteins. Whole blood and platelet adhesion was reduced by ~92% on CH-Q, which
showed the weakest interaction with plasma protein but more viscous adsorbed
plasma protein layer, compared to SiO2. Last, to examine the biologic response of
platelets and neutrophils to biomaterial surfaces, CH (CH-Q)/PAA, PAA and PU
tubes were tested using a Chandler Loop apparatus as an ex vivo model and flow
cytometry. The blood adhesion and biologic response results showed that CH and CH
Q reduced adhesion and activation of platelets and neutrophils and improved
hemocompatibility relative to other surfaces (PU and PAA). Our studies
demonstrated that the properties of physically adsorbed plasma protein layer on
biomaterial surfaces correlates with blood coagulation on biomaterial surfaces.
PMID- 24349720
TI - Determinants of inequity in health care services utilization in markazi province
of iran.
AB - BACKGROUND: National and international statistics from Iran have indicated that
progresses and achievements have been made for most health indicators, but there
are differences in some indicators in special groups and at the provincial level.
OBJECTIVES: Our aim was to assess the main predictors of inequity in seeking
Health Care Utilities (HCU) locally. PATIENTS AND METHODS: Data gathered from the
HCU survey, which was conducted in the Markazi province of Iran during 2008, was
used in the present study. A systematic sampling method, based on the Iranian
household framework, was applied in order to choose 758 households as well as
2711 individuals. The household wealth index constructed by Principle Component
Analysis (PCA) and robust login link function in Generalized Estimation Equation
(GEE) model were used in order to determine the predictors of inequity. RESULTS:
66.4% of those in need sought outpatient health care from which 97.7% received
appropriate services. After adjustment for the clustering effect of household as
well as confounding effect of the covariates, GEE model showed that there were
inequities in HCU for females (OR = 2.44, CI; 1.24- 4.81) and subjects with
inpatient need (OR = 2.14, CI: 1.23-3.72). Being in the lowest quintile of
household wealth index was associated with the lower use of outpatient health
services (OR = 0.45, CI; 0.23- 0.88). CONCLUSIONS: In spite of improvements in
the national health indicator, different groups of people use health care
services differently, but these inequities in HCU are related to social and
individual factors. Also, it is clear that health sector facilities and the
accessibility to health services are not the only predictors.
PMID- 24349721
TI - Genetic Analysis of cagA and vacA Genes in Helicobacter Pylori Isolates and Their
Relationship with Gastroduodenal Diseases in the West of Iran.
AB - BACKGROUND: Helicobacter pylori have different virulence factors which are
associated with several gastroduodenal diseases; however, this association is
variable in different geographical regions. Data of genotypes of Iranian H.
pylori isolates are few. OBJECTIVES: The aim of the current study was to
investigate the cagA/vacA genotypes of Helicobacter pylori isolates and determine
the relationship between these genotypes with respect to different gastric
disorders in patients of Chaharmahalo Bakhtiarian. MATERIALS AND METHODS: In this
cross-sectional study, gastric biopsies were taken from 200 patients with
gastrodoudenal diseases. Histopathological features were recognized by
specialist. The samples were subjected to PCR for detection and identification of
ureC, cagA and vacA genes. RESULTS: The frequency of the vacA genotypes, sa1/m1,
s1a/m1b, s1a/m2, s1b/m1a, s1b/m1b, s1b/m2, s1c/m1a, s1c/m1b, s1c/m2, s2/m1a,
s2/m1b and s2/m2 were 27(6.6%), 8(4.3%), 45(28.04%), 7(3.7%), 5(2.5%), 10 (6.1%),
12 (7.4%), 4 (2.5%), 18(11%), 6(3.7%), 0 and 22(13.5%) respectively. The cagA
gene was detected in 92% of strains. Based on our findings, it seemed that cagPAI
and vacA s1 genotypes were associated with some gastric disorders in patients
with H. pylori. In this region, the isolates carrying s1a/m2 were the most
prevalent. CONCLUSIONS: We found considerable relationship between s1a/m1a,
s1a/m2, s2/m2 and s1c/m1a and some gastric disorders. Further studies about the
role of H. pylori virulence factors and gastric disorders were recommended.
PMID- 24349722
TI - Detection of sugar chain expression in hydatidiform mole using lectin
histochemistry.
AB - BACKGROUND: Hydatidiform moles carry a significant risk for developing persistent
gestational trophoblastic disease. Lectins are useful tools to identify cellular
glycosylation pattern and changes in glycosylation that occur during growth,
development, differentiation and also, during disease states. OBJECTIVES:
Considering the changes in glycosylation that occur during cell proliferation,
differentiation and transformation, the aim of the present study was to evaluate
the sugar chain expression in hydatidiform mole by using HRP-conjugated lectins.
MATERIALS AND METHODS: Lectin histochemistry with a panel of HRP-conjugated
lectins comprising SBA, PNA, VVA, UEA-1, LTA, GS-I (B4) and WGA were performed in
20 molar (partial & complete moles) formalin-fixed, paraffin-embedded tissue
samples. RESULTS: The partial and complete moles generally showed similar
reactivity with all used lectins. None of lectins reacted with villous
cytotrophoblasts, whereas 4 of 7 lectins comprising WGA, LTA, UEA-I and PNA
(after pretreatment with neuraminidase) showed a moderate to strong reactivity
with villous syncytiotrophoblasts in both partial and complete hydatidiform
moles. The villous stroma reacted with all used lectins except VVA. CONCLUSIONS:
Our histochemical findings showed a relatively heavy glycosylation of
syncytiotrophoblasts of both partial and complete molar tissues, which was
prominent in apical portion. This may play a role in their capacity to increase
trophoblastic proliferation.
PMID- 24349723
TI - Accuracy of endotracheal tube cuff pressure adjustment by fingertip palpation
after training of intensive care unit nurses.
AB - BACKGROUND: Untrained fingertip palpation has been shown to be unable to adjust
endotracheal tube (ET) cuff pressure in most intubated patients. OBJECTIVE: We
determined the impact of a training course of ETT cuff adjustment by palpation in
attaining a safe cuff inflation pressure. PATIENTS AND METHODS: Twenty-five
nurses were asked to adjust the ETT cuff pressure to 25 cmH2O by palpation on
three different patients in seven sessions (S1-S7): before training, two hours
and two days after first training session, and two hours, two days, one week, and
eight months after second training session. RESULTS: Before training, 41.3% of
the cuff pressures were adjusted to the safe range of 21-35 cmH2O. The pressures
obtained in S2-S7 were lower and less variable than S1 (P = 0.02 to < 0.0001).
After the first training session, all the ETT cuff pressures in the high range
(36-50 cmH2O) and 87.5% in the very high range (> 50 cmH2O) changed to the safe
range. CONCLUSIONS: Using trained fingertip adjustment of the ETT cuff pressure
throughout the nursing shift with protocols for the adjustment of out of range
pressures at the beginning of each shift by cuff manometer could decrease the
rate of ETT cuff over- and under-inflation.
PMID- 24349724
TI - Comparison of Knifelight Surgery versus Conventional Open Surgery in the
Treatment of Carpal Tunnel Syndrome.
AB - BACKGROUND: A variety of surgical treatment methods for carpal tunnel syndrome
are introduced recently, including open surgery, endoscopic and the Knifelight.
It is hypothesized that Knifelight method could decrease scar tenderness and time
before return to daily activities for patients and is accompanied with less
disturbance to fine sensory nerves. OBJECTIVES: To compare the Knifelight
instrument and open carpal tunnel release with respect to scar length, operation
duration, recovery time needed before return to work and amount of pain three
weeks after surgery in patients with neurophysiologically confirmed carpal tunnel
syndrome. PATIENTS AND METHODS: FIFTY NINE PATIENTS WITH INDICATION FOR CARPAL
TUNNEL RELEASE RANDOMLY ASSIGNED INTO TWO GROUPS: open (n=30) or Knifelight
(n=29). The patients compared regarding scar length, operation duration, time to
return to daily activities and amount of pain at three weeks after operation
based on Visual Analog Scale. RESULTS: There was no significant differences
regarding age and sex in the two groups. The scar length, operation duration and
time before return to daily activities were significantly lower in the Knifelight
group. Although the mean visual analogue scale of Knifelight group found to be
lower than the other, it was not statistically significant. CONCLUSIONS: The
Knifelight technique is accompanied with advantages over the open surgery
regarding operation time, scar length and time to return to daily activities. The
pain relieve based on Visual Analog Scale was not statistically different from
conventional open surgery.
PMID- 24349725
TI - The role of diminishing appetite and serum nesfatin-1 level in patients with burn
wound infection.
AB - BACKGROUND: The burn wound represents a susceptible site for opportunistic
colonization by organisms of endogenous and exogenous origin. Diminishing
appetite is known to occur in patients with burn infection, yet its underlying
reason is not fully understood. We have examined the levels of nesfatin 1, a
protein that we consider to be a potential new treatment target for the solution
of appetite and nutrition problem in patients with burn infection. OBJECTIVES:
The aim of the present study was therefore to examine nesfatin levels in patients
with burn infection. MATERIAL AND METHODS: Laboratory values, medication and
dietary records, and patient notes with diagnostic information of burn wounds
patients who were admitted to the Division of Burn Treatment Center were obtained
from the Erzurum Region Education and Research Hospital electronic database. Post
burn wound infection was objectively assessed by culturing wound homogenates from
skin tissue. The main immediate inflammatory stress response parameters assessed
were serum CRP concentrations, WBC counts, and blood nesfatin concentrations.
RESULTS: Scalding was the predominant cause of burns in both categories of
patients. In 19 (61.3%) burn wound infection patients, the burns were due to a
scald. A significant difference was found for the nesfatin, CRP, and WBC levels
between the patients and the control group (P = 0.000). A significant difference
was also determined between the nesfatin, CRP, and WBC figures at the time of
hospitalization and at discharge from the hospital (P = 0.000). The most
predominant bacterial isolate was Pseudomonas aeruginosa 16 (51.6%) followed by
Methicilline resistant Staphylococcus aureus (MRSA) 7 (22.6%). CONCLUSIONS: We
showed that the serum nesfatin 1 level was significantly lower in the patients
with burn than in the control group in our study. We considered that the central
nesfatin 1 system should be taken into consideration, rather than the peripheric
nesfatin 1 system, when considering the regulation of appetite in patients with
burns and particularly those accompanied by infection. In other explanation of
the observed negative correlation between nesfatin 1 and burn wound infection
suggests that nesfatin 1 may indicate the possible contribution of nesfatin 1 to
the energy homeostasis.
PMID- 24349726
TI - The efficiency and budgeting of public hospitals: case study of iran.
AB - BACKGROUND: Hospitals are the most costly and important components of any health
care system, so it is important to know their economic values, pay attention to
their efficiency and consider factors affecting them. OBJECTIVE: The aim of this
study was to assess the technical scale and economic efficiency of hospitals in
the West Azerbaijan province of Iran, for which Data Envelopment Analysis (DEA)
was used to propose a model for operational budgeting. MATERIALS AND METHODS:
This study was a descriptive-analysis that was conducted in 2009 and had three
inputs and two outputs. Deap2, 1 software was used for data analysis. Slack and
radial movements and surplus of inputs were calculated for selected hospitals.
Finally, a model was proposed for performance-based budgeting of hospitals and
health sectors using the DEA technique. RESULTS: The average scores of technical
efficiency, pure technical efficiency (managerial efficiency) and scale
efficiency of hospitals were 0.584, 0.782 and 0.771, respectively. In other words
the capacity of efficiency promotion in hospitals without any increase in costs
and with the same amount of inputs was about 41.5%. Only four hospitals among all
hospitals had the maximum level of technical efficiency. Moreover, surplus
production factors were evident in these hospitals. CONCLUSIONS: Reduction of
surplus production factors through comprehensive planning based on the results of
the Data Envelopment Analysis can play a major role in cost reduction of
hospitals and health sectors. In hospitals with a technical efficiency score of
less than one, the original and projected values of inputs were different;
resulting in a surplus. Hence, these hospitals should reduce their values of
inputs to achieve maximum efficiency and optimal performance. The results of this
method was applied to hospitals a benchmark for making decisions about resource
allocation; linking budgets to performance results; and controlling and improving
hospitals performance.
PMID- 24349727
TI - The association between melasma and postinflammatory hyperpigmentation in acne
patients.
AB - BACKGROUND: Although, melasma is most prevalent among Asian young women, and also
darkly pigmented individuals are particularly prone to developing post
inflammatory hyperpigmentation, to the best of our knowledge, there are rare or
no studies about the association of melasma and Post inflammatory
hyperpigmentation. OBJECTIVES: The aim of this study was to investigate how
likely is a melasma patient to developed post inflammatory hyperpigmentation when
compared to patients with inflammatory acne lesions who do not have melasma.
PATIENTS AND METHODS: This comparative study was conducted on 400 participants,
200 subjects involved with pigmented lesions of melasma and inflammatory acne
lesions and200 involved only with inflammatory Acne lesions without melasma.
Melasma, acne and post inflammatory hyper pigmentation, if existed, were assessed
by a dermatologist, and pigmentation depth was assessed by wood's lamp.
Multivariate logistic regression analysis suitable for study design was used to
assess the association between melasma and post-acne pigmentation. RESULTS: We
found out that 24.1% of patients without melasma had post-acne pigmentation
compared to 66.8% in melasma group (P < 0.001). The likelihood of observing post
acne pigmentation was found to be nearly six times more in melasma patients
versus those without melasma. Association existed after controlling for possible
confounders such as melanin score and time length of self-reported sun exposure,
and acne severity score. CONCLUSIONS: Melasma appears to increase the likelihood
of post-acne pigmentation.
PMID- 24349728
TI - The reliability and validity of the persian version of sinonasal outcome test 22
(snot 22) questionnaires.
AB - BACKGROUND: The quality of life (QOL) is an important indicator for disease
severity classification and outcome measurement in obtaining treatment sinonasal
diseases. The sinonasal outcome test 22 (SNOT 22) questionnaire has been
introduced as the best specific sinonasal instrument for QOL measurement.
OBJECTIVES: To prepare a valid and reliable Persian language version of SNOT 22
questionnaire. PATIENTS AND METHODS: After forward and backward translation of
the original version of SNOT 22 questionnaire from English to Persian, a group of
patients with nasal septal deviation who need septal surgery and another group of
healthy volunteers answered the Persian version of the questionnaire. The
responsiveness rate, validity (Pearson correlations and differential validity)
and reliability (internal consistency and test-retest reliability) of the 22
items of the questionnaire was calculated. P value < 0.05 was considered
significant. RESULTS: Thirty adults with nasal septal deviation need surgical
correction and 30 healthy volunteers were included (mean age 30.4 +/- 7.1 vs. 33
+/- 6.7, P value = 0.148). The questionnaire was introduced to subjects two times
with a two-week-period gap. Total responsiveness rate for 22 items was more than
97%. The total Cronbach's Alfa coefficient was 0.898 (ranging 0.890-0.903). The
Pearson correlations were 0.85 and 0.96 for patients and healthy volunteers,
respectively. The mean total score were 25.6 +/- 13.3 (range 6-52) and 7.6 +/-
9.1 (range 0-45) in patients and healthy volunteers, respectively (P < 0.0001).
The subscales scores were also significantly different between two groups.
CONCLUSIONS: The Persian version of SNOT 22 questionnaire is a valid and reliable
instrument for accessing sinonasal diseases in Persian-speaking people.
PMID- 24349729
TI - Hepatitis a virus seropositivity in nurses and paramedical personnel at a
university hospital in north iran.
AB - BACKGROUND: The status of hepatitis A virus (HAV) among health care workers has
not been studied yet in Iran. OBJECTIVES: This study aimed to evaluate the HAV
seropositivity among the healthcare personnel in Ayatollah Rohani Hospital,
Babol, Iran, according to age, number of working years, and other demographic
data. PATIENTS AND METHODS: This cross sectional study was performed on all
nurses, nurses' aid, and paramedical technicians at Ayatollah Rohani Hospital,
Babol, from March 2011 to March 2012. Blood was obtained from all cases (466) and
the sera were separated. All serum samples were tested for anti-HAV antibodies
(IgG) by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by
logistic regression analysis using SPSS software, version 18. RESULTS: 330 out of
466 (71%) persons were positive for anti-HAV antibodies (IgG) with no significant
difference between females (71.5%) and males (70%) (P = 0.89, 95% CI. 0.533
2.083). The lowest sero-prevalence rate was observed in the 20-29 year age group
(57.8%). Seropositivity for HAV significantly increased with age (P < 0.000, 95%
CI. 1.626-3.262), 77.4% for 30-39 years and 85.3% for more than 40 years. The
seropositivity rate also increased significantly in accordance with the number of
working years (P = 0.012, 95%CI. 1.098-2.170). 110 out of 353 (31.2%) cases were
seronegative among those with less than 5 years of working time. An obvious
decrease of seronegative rate of HAV was seen in those with 5-10 years (27%) and
more than 10 years (14.3%) of working time. CONCLUSIONS: These findings indicate
relatively high prevalence rate of HA infection among nurses and paramedical
personnel at this hospital. Nevertheless, 30% of the health workers have been
seronegative and are still at risk of HA infection development. Considering that
the disease has more severe course as age increases, improvement of standard
hygiene and prevention strategies are recommended. Furthermore, vaccination may
play a significant role in the occupational health policy to protect the
susceptible health care workers population in the future.
PMID- 24349730
TI - The effect of systemic arterial-line leukocyte filtration on the outcome of adult
patients undergoing cardiac surgery.
AB - BACKGROUND: It is known that cardiopulmonary bypass causes an inflammatory
reaction with associated morbidity and mortality. Several anti-inflammatory
strategies have been implemented to reduce this response, including leukocyte
removal from the circulation using specialized filters. OBJECTIVES: The aim of
this randomized clinical study was to assess the impact of arterial-line systemic
leukocyte filtration on the postoperative outcome of adult patients undergoing
elective cardiac surgery. PATIENTS AND METHODS: 114 patients undergoing CABG or
valve replacement in Baqiyatallah hospital, Tehran, Iran from May to August 2011
were randomly assigned to two groups: with and without leukocyte filtration and
their outcomes were compared. RESULTS: The postoperative intubation time was
significantly shorter in patients with leukocyte filters (0.014). There was no
significant difference between two groups regarding other outcome
relatedvariables. CONCLUSIONS: Systemic arterial leukocyte filtration reduces the
intubation time but has no other beneficial effect on the outcome of patients
undergoing CABG or valve surgery.
PMID- 24349731
TI - Historical cohort study on the factors affecting blood pressure in workers of
polyacryl iran corporation using bayesian multilevel modeling with skew T
distribution.
AB - BACKGROUND: Hypertension is considered as a major public health problem in most
countries due to its association with ischemic heart disease which causes
cerebrovascular disease and death. OBJECTIVES: The purpose of the present study
was to study factors affecting Blood Pressure (BP). PATIENTS AND METHODS: The
data were extracted from annual observation of the workers who worked in
Polyacryl Iran Corporation (PIC) between 1998 and 2010. In this research, we
assessed the effect of Body Mass Index (BMI), age, sex, job status, marital
status, job schedule type, and education level on Systolic Blood Pressure (SBP)
and Diastolic Blood Pressure (DBP) using Bayesian multilevel modeling with skew t
distribution using WinBUGS software. RESULTS: Totally 3965 persons participated
in this study, 75(1.9%) female and 3890 (98.1%) male. In this study age, sex,
BMI, job status, marital status, and education level had statistical association
with SBP. The result for DBP was similar to SBP except the education level which
had no statistical association. CONCLUSIONS: Treating obesity, increasing
physical activity and quality of married life are proposed as practical solutions
to reduce BP.
PMID- 24349732
TI - Comparing remifentanil versus propofol effect on pain and homodynamic change of
patients undergoing phacoemulsification with topical anesthesia.
AB - INTRODUCTION: The purpose of this study was to compare remifentanil versus
propofol effect on pain and homodynamic in patients undergoing
phacoemulsification with topical anesthesia. MATERIALS AND METHODS: A double
blind clinical trial was conducted to research following the approval of the
ethical committee research of the university. One hundred volunteer subjects were
randomly assigned into two equal groups (n = 50). The subjects in the propofol
group received 3mg/kg/hr while the patients in the remifentanil drug received 3
ug/kg/hr of this medication. Phaco time, blood pressure and heart rate before and
after surgery, respiratory depression (O2 sat < 90%) and vomiting, pain scores,
ophthalmologist satisfaction and demographic data were recorded. RESULTS: The
results of analysis showed that there were no significant differences between the
age, sex, and duration of operation of the two treatment groups. Systolic,
diastolic blood pressure and heart rate were significantly lower in the propofol
group .The propofol group complained of pain than the remifentanil group (P =
0.001) while the surgeon satisfaction was higher for the remifentanil condition
(P = 0.01). No significant differences were found between the two groups with
respect to respiratory depression .No patient suffered from nausea and vomiting.
CONCLUSIONS: The results of this study indicated that using appropriate dose of
remifentanil instead of propofol results in less pain, more stable homodynamic
condition, and satisfaction of surgeon without no respiratory depression or
perioperative nausea and vomiting.
PMID- 24349733
TI - Histologic evaluation of human pulp response to total etch and self etch adhesive
systems.
AB - BACKGROUND: To investigate pulp response to the application of two types adhesive
systems (total-etch and self-etch) in human premolar teeth. MATERIALS AND
METHODS: Cavities limited to enamel walls in all margins with 2.5 mm depth were
prepared on buccal surfaces of thirty three human premolars. The cavities were
treated with the following adhesive. Single Bond (SB) and Prompt L-Pop (PLP). The
teeth were extracted after 30 days and prepared due to histological technique.
RESULTS: Pulp responses were evaluated in three field including inflammatory cell
response, pulp tissue disorganization and restorative dentin formation. There
were no differences in histological response of the pulp tissue (P > 0.05).
CONCLUSION: Both adhesive systems showed good biological compatibility.
PMID- 24349734
TI - Clinical outcome of ream versus unream intramedullary nailing for femoral shaft
fractures.
AB - BACKGROUND: Stabilization of fractures with an intramedullary nail is a
widespread technique in the treatment of femoral shaft fractures in adults;
however, to ream or not to ream is still being debated. OBJECTIVES: The primary
objective of this study was to determine clinical results following unreamed
versus ream intramedullary nailing of femoral fractures. PATIENTS AND METHODS:
Between January 2008 and August 2009, 50 patients with femoral shaft fractures
were treated with unreamed or reamed femoral nails in our clinic. From this
prospective single centre study, 16 patients were excluded due to insufficient
follow-up data. According to the AO classification, fractures in this study were
either type A or B. Dynamic proximal locking was performed in all cases. The
remaining 34 patients were divided into two groups of 17 with ream or unream
nailing. During and after the operation, we evaluated some variables in whole
series. RESULTS: After statistical analyzes, we found that there were no
differences in radiologic union time (P = 1) or full weight bearing time (P =
0.73) between ream and unream nailing. Nail breakage or iatrogenic fractures
during nail insertion did not occur and we did not have any fat emboli in both
groups but one secondary loss of reduction occurred in the unream group.
Superficial infection after the operation was seen in one case which was treated
successfully with antibiotics. In the ream group surgical time was about thirty
minutes longer and differences were significant (P = 0.000). Patients had to pay
more for ream nailing but the difference was not significant. We found no
statistical difference between union time with or without reaming; on the other
hand, there was significant increased operation length, blood loss and systemic
changes in BP or So2 in the ream group versus the unream group. CONCLUSIONS: We
advocate that unream nailing in traumatic femoral shaft fractures is a simple,
safe and effective procedure with significant advantages, especially in
multitrauma patients.
PMID- 24349735
TI - Nocardiosis: risk factors, clinical characteristics and outcome.
AB - Nocardiosis has been reported increasingly in recent two decades, probably due to
improvement in isolation of the organism and increased burden of immune
compromised patients. Nocardia occasionally has been reported in healthy people.
A case series of definitive Nocardiosis (2002 to 2010), clinical characteristics,
underlying diseases, immune status and in-patient outcome were studied in a
tertiary referral center. Twenty one patients with definite diagnosis of
Nocardiosis were studied. 17 cases (81%) had an underlying disease (diabetes
mellitus, corticosteroid therapy, and chronic granulomatous disease and collagen
vascular diseases). Four patients (19%) were immune-competent without any
predisposing disease. In 17 patients (81%), Nocardiosis was limited to
respiratory tract and in 4 cases (19%) it was disseminated with multi organ
involvement. Two cases (9.5%) died in hospital.
PMID- 24349736
TI - Prediction of milk consumption among Iranian pregnant women: application of the
theory of planned behavior.
PMID- 24349737
TI - Comparison of the Effects of Powdered and Powder-free Surgical Gloves on
Postlaparotomy Peritoneal Adhesions in Rats.
PMID- 24349738
TI - Determination and Comparison of Affecting Two Methods of Self-aid and Body-aid
Based on the Multimedia Software Packages Method and the Lecturing on the Amount
of Knowledge and Operation of Personals of Selected Combat Battalions.
PMID- 24349739
TI - Electrocardiologic and echocardiographic findings in patients with scorpion
sting.
PMID- 24349740
TI - Comparison of the Effect of 8 weeks Aerobic and Yoga Training on Ambulatory
Function, Fatigue and Mood Status in MS Patients.
AB - BACKGROUND: Multiple Sclerosis (MS) is a disease of the central nervous system
that results in many symptoms including mobility limitation and fatigue. PATIENTS
AND METHODS: Thirty-one MS patients, all female with mean of age of 36.75 years
and Expanded Disability Status Scale scores (EDSS) of 1.0 to 4.0 were recruited.
Subjects were randomly assigned to one of the three groups: treadmill training,
yoga or control groups. Treadmill training and yoga practice consisted of 8 weeks
(24 sessions, thrice weekly). The control group followed their own routine
treatment program. Balance, speed and endurance of walking, fatigue, depression
and anxiety were measured by Berg Balance scores, time for 10m walk and distance
for a two minute walk, Fatigue Severity Scale (FFS), Beck Depression Inventory
(BDI) and Beck Anxiety Inventory (BAI), respectively. RESULTS: Comparison of
results have shown that pre- and post-interventions produced significant
improvements in the balance score, walking endurance, FFS score, BDI score and
BAI score in the treadmill training group and yoga group. However, 10m walk time
decreased in the treadmill training group but did not show any clear change in
the yoga group. Moreover, the analysis showed significant differences between the
treadmill training group and yoga group for BAI score. CONCLUSIONS: These results
suggest that treadmill training and yoga practice improved ambulatory function,
fatigue and mood status in the individuals with mild to moderate MS.
PMID- 24349742
TI - Path analysis of the risk of low birth weight for multipara.
AB - BACKGROUND: LBW rate is one of the most important health indices in every
society. It reveals mothers and their new-born infants' health. OBJECTIVES: Our
aim, in the present paper, was to present a new statistical framework for
analysis based on path analysis techniques. PATIENTS AND METHODS: A prospective
study was conducted in two maternity wards, (privet & governmental hospital) in
Sari, Iran. In this research a check-list containing 25 questions about mother's
demographic information and her new-born infant was prepared. Every new born
infant who was born weighing less than 2500 g was entered in our study and just
next the newborn infant who was normal all of his/her information use to be taken
too, (n = 190). Path analysis, an extension of the regression model, was used in
this study. RESULTS: Obviously exactly half of the infants were LBW, and the
remainder were normal. There were 97 boys and 93 girls. The percentage of IUGR
among mothers who had preterm delivery was 19, while this percentage for mothers
who had term delivery was 11.5 (P value = 0.167). LBW infants were 36.7%
unexpected, while this percent for normal infants was 15.5 (P value < 0.001).
Preterm delivery has a significant and direct effect on LBW (p value < 0.001),
and its positive sign of path coefficient shows that if it occurs, the
probability of LBW will increase, the second important was IUGR, the results
showed unexpected pregnancy had direct effect on LBW but this wasn't significant
(P value = 0.292). CONCLUSIONS: By preventing unnecessary termination of
pregnancy and keeping fit, the chances of LBW can be reduced.
PMID- 24349741
TI - The small round blue cell tumors of the sinonasal area: histological and
immunohistochemical findings.
AB - BACKGROUND: Primary Small round blue cell tumors (SRBCT) in sinonasal comprise
histogenetically diverse entities with overlapping morphologic features. Because
of the limited initial biopsy tissue materials, differential diagnostic
difficulties may arise, and as they have different management, exact diagnosis
and classification are very important. OBJECTIVES: In this study, we analyzed the
immunohistochemical expression of a panel of markers in the classification and
diagnosis of sinonasal SRBCTs. MATERIAL AND METHODS: This cross sectional study
was performed on 36 paraffin embedded tissue samples. Histologic and
immunohistochemical slides from 36 patients with SRBCT were analyzed
retrospectively. The patients were admitted in Khalili hospital, Shiraz from 1383
to 1388. RESULTS: There were 13 women and 23 men with the mean age of 53 +/-12.1.
There were 9 malignant melanoma, seven poorly differentiated SCC; six lymphoma
(DLBL); 4 SCNEC; three SNUC; two ON; two Ewing/PNET; two embryonal
rhabdomyosarcoma, and one plasmacytoma. Pan-cytokeratin was strongly expressed
poorly differentiated SCC and all cases of SNUC. Coexpression of desmin and
nuclear myoD1 was only detected in rhabdomyosarcoma. HMB45 was only expressed in
sinonasal melanoma. CD99 expression was identified only in Ewing/PNET. FLI-1 was
detected in 50% of PNET. P63 was expressed in poorly differentiated SCC (2/7) and
SNUC (1/3). CONCLUSIONS: The results of our study indicate that the integration
of histopathologic findings with application of limited but highly specific
markers led to the separation of carcinomas, lymphoma and melanomas from other
small cell tumors. Using a panel of keratin, LCA, desmin, and HMB45 is the most
practical and economic approach to accurately classify these tumors.
PMID- 24349743
TI - Clinical lipid control success rate before and after percutaneous coronary
intervention in iran; a single center study.
AB - BACKGROUND: High cholesterol levels have long been considered an independent risk
factor for cardiovascular disease (CVD). OBJECTIVE: Controlling risk factors such
as dyslipidemia in patients with coronary artery disease is necessary. We aimed
to evaluate the success rate of lipid control, during 9 months follow-up after
percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 195
patients (67.7% men, mean age = 57.8 +/- 9.4 years) who underwent PCI in Tehran
Heart Center were included. Serum lipid profiles were measured in all the
patients before PCI and at 9-month follow-up. Dyslipidemia was defined as serum
levels of LDL-C >= 100 or TG >= 150 or TC >= 200 or HDL-C <= 40 mg/dl in the men
and <= 50 mg/dl or less in the women, or non-HDL-C >= 130 mg/dl with or without
the consumption of lipid-lowering agents. During follow up, all patients were
given atorvastatin 20-40 mg/day. RESULTS: Overall, 26.2% had diabetes mellitus,
42.6% had hypertension, and 34.9% were smokers. Dyslipidemia was more common in
the women. At 9-month follow-up, there was no significant changes in terms of the
prevalence of high HDL-C or low TG in patients; however, a significant increase
was seen in the prevalence low TC in patients (63.6% vs. 80.5%; p value < 0.001),
LDL-C (47.2% vs. 65.6%; p value < 0.001), and non-HDL-C (40.0% vs. 63.1%; p value
< 0.001). CONCLUSIONS: Although by current treatments, the prevalence of patients
with low TC, LDL-C and non-HDL-C has significantly increased; dyslipidemia
persisted in a considerable proportion of patients. These results necessitate
further investigations into the relationship between high serum lipids and long
term outcome of patients after PCI as well as further evaluations of the
dyslipidemia treatment strategies.
PMID- 24349744
TI - Frequency of all types of colorectal tumors in the patients referred to selected
hospitals in tehran.
AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide
which is not extensively researched in Iran. OBJECTIVES: The present study aims
to investigate the epidemiologic characteristics of CRC in patients referred to
selected hospitals of Tehran University of Medical Sciences. PATIENTS AND
METHODS: In this descriptive-analytic study 218 patients with colorectal cancer
were investigated. Data were collected via reviewing recorded pathologic results
of patients of these hospitals which then were analyzed by univariant methods.
RESULTS: Among 218 patients, 140 (64.2%) were male and 78 (35.8%) were female. Of
all patients, 132 (60.0%) suffered from tumors in rectum; 38 (17.4%) in sigmoid;
12 (5.5%) in descending colon; 10 (4.6%) in transverse colon and 26 (11.9%) in
ascending colon and cecum. Tumors were well differentiated in 134 patients
(61.5%), moderately in 62 cases (28.4%) and poorly differentiated in 22 patients
(10.1%). There was no significant difference between males and females regarding
the location and degree of tumor differentiation. CONCLUSIONS: Regarding high
prevalence of colorectal cancer in Iran and potential environmental and genetic
factors, surveillance must be considered for this disease. Its risk factors such
as diet, life style and low physical activity should be evaluated and screening
should start at younger ages.
PMID- 24349745
TI - Determining the Latent Tuberculosis Infection by IFN - gamma Elispot Assay in
Healthcare Workers From University Hospitals of Shiraz, South West of Iran.
AB - BACKGROUND: Classical screening methods are incapable to properly detect LTBI
(Latent TB Infection) and HCWs (Healthcare Workers) are at the high risk of
exposure. Only few reports estimated the prevalence of LTBI among Iranian HCWs
and they mostly used the TST (Tuberculin Skin Test), rather than assessing the
response against TB-specific antigens. OBJECTIVES: The current study aimed to
determine the frequency of IFN - gamma producing blood cells of microbiology and
radiology ward technicians by an in-house IFN - gamma ELISPOT assay in the
University hospitals of Shiraz University of Medical Sciences (SUMS) against
recombinant ESAT - 6 and PPD antigens. MATERIALS AND METHODS: 89 HCWs from
medical laboratory and radiology departments of Shiraz University of Medical
Sciences' hospitals, South of Iran, were screened for LTBI. To achieve the goal,
an in-house IFN - gamma (Interferon - gamma) ELISPOT (Enzyme Linked ImmunoSpot)
assay was used to detect the reactivity against ESAT - 6 (Early Secreted Antigen
Target protein - 6) and the PPD (Purified Protein Derivate). RESULTS: Almost 8%
of the personnel showed positive TST (over 10 mm) reaction while 29% of them had
considerable T - cell reactivity against PPD in ELISPOT assays. However, the ESAT
- 6 reactivity was found only in one case of HCWs. No correlation was found
between the patterns of the reactions and the age or the duration of the
employment or previous vaccination history of the participants. The ELISPOT
results were not correlated with the TST results. CONCLUSIONS: Considering the
hindrance of TST, the IFN - gamma ESAT - 6 ELISPOT assay, even in forms of in
house tests, could replace traditional methods to properly spot the LTBI among
the high risk groups from Iran's health system.
PMID- 24349746
TI - Comparing the effect of preoperative administration of methylprednisolone and its
administration before and during surgery on the clinical outcome in pediatric
open heart surgeries.
AB - BACKGROUND: Cardiac surgery under Cardiopulmonary bypass causes a systemic
inflammatory response with a multifactorial etiology including direct tissue
damage, ischemia and stimulation of immune system induced by cardiopulmonary
bypass. This study was designed due to the high prevalence and complications of
this stimulated immune system in mortality, morbidity, length of ICU stay, and
mechanical ventilation. OBJECTIVES: This study was aimed to compare preoperative
and intraoperative methylprednisolone (MP) to intraoperative MP alone with
respect to postbypass inflammation and clinical outcome. PATIENTS AND METHODS:
Sixty pediatric patients (age < 5years) undergoing cardiopulmonary bypass surgery
between September 2011-2012 at Imam Reza hospital-Mashhad were randomly assigned
to receive preoperative and intraoperative MP (group 1: 30 mg/kg, 4 hours before
bypass and in bypass prime, n = 30) or intraoperative MP only (group 2: 30 mg/kg,
n = 30). Postoperative temperature (peak temperature and average temperature
during the first 24 hours), amount of inotropic, duration of mechanical
ventilation, ICU stay, WBC, BUN, creatinine, and CRP were recorded and compared
in both groups. Data were analyzed with SPSS version 13 by T-test, Mann-Whitney
test if necessary, and Chi-squared distribution. RESULTS: Patient characteristics
including age, weight, gender, and duration of bypass were almost similar in both
groups (P > 0.05). No significant difference in amount of inotropic medications
used for hemodynamic supports, duration of mechanical ventilation, peak and
average temperature and length of ICU stay was observed. Among the laboratory
tests (WBC, BUN, creatinine, CRP) only WBC counts raised more in group 2 when
compared to group 1(P < 0.05). CONCLUSIONS: There was no difference in clinical
outcome after cardiac surgery when we administered an additional dose of
methylprednisolone compared to a single dose of methylprednisolone.
PMID- 24349747
TI - Comparison of vessel sealing systems with conventional.
AB - BACKGROUND: Haemorrhoids are cushions of submucosal vascular tissue located in
the anal canal starting just distal to the dentate line. Haemorrhoidal disease is
a common anorectal disorder which has symptoms of bleeding, prolapse, pain,
thrombosis, mucus discharge, and pruritus. Haemorrhoidectomy is one of most
frequently performed anorectal operation worldwide. OBJECTIVES: The aim of this
study was to compare the effectiveness of the LigaSure tissue sealing device,
Harmonic Scalpel and conventional MM open haemorrhoidectomy. MATERIALS AND
METHODS: Sixty-nine patients with newly diagnosed symptomatic grade three or
grade four haemorrhoidal disease, from July 2011 to December 2011 were recruited
for the study. Patients were prospectively randomized to LigaSure, Harmonic
Scalpel and conventional haemorrhoidectomy. Patients were evaluated on the basis
of the mean operative time, postoperative pain, day of discharge, early and late
complications. RESULTS: Each group has twenty-three patients. Ten (14.5 %) were
female and fifty-nine (85.5 %) were male. Mean age were 44.5 +/- 10.8 for
LigaSure group, 39.5+/-14.4 for Harmonic Scalpel group and 39.8 +/- 13.6 for
conventional haemorrhoidectomy group. Mean operative time was 12.6 +/- 2.9 for
LigaSure group, 12.6 +/- 2.5 for Harmonic Scalpel group and 22.3 +/- 4.5 for
conventional haemorrhoidectomy group. Postoperative pain and required analgesic
dose were significantly lower for conventional haemorrhoidectomy. Wound healing
was also more rapid in conventional haemorrhoidectomy than both LigaSure and
Harmonic Scalpel. CONCLUSIONS: Lateral heat dissipation of energy based cautery
such as Harmonel Scalpel and LigaSure is considerably high when compared with
conventional methods. More thermal damage which is generated on tissue seems to
be the reason for increased degree of postoperative pain and delay in wound
healing.
PMID- 24349748
TI - Perforated acute appendicitis in a pre-term neonate.
AB - Acute appendicitis is a common occurrence in childhood, but this diagnosis is
considered rarely in differential diagnosis of acute abdomen in the neonatal
period because its occurrence is very rare in neonates. We report a 20-day- old
afghan female baby that was admitted to neonatal intensive care unit, because of
irritability and abdominal distension. Complete ultrasound of abdomen and pelvis
was normal. In plain Radiographs of chest and abdomen with the exception of Air
filled stomach and intestine, there was no abnormality. Due to the lack of
improvement and severe abdominal distension, she was transmitted to the operating
room and Surgical exploration revealed perforated appendix. Appendicitis should
be considered in the differential diagnosis for a neonate with abdominal
distension and bilious vomiting and needs strong clinical suspicion.
PMID- 24349749
TI - Comparison of three interview methods on response pattern to sensitive and non
sensitive questions.
AB - BACKGROUND: To get more precise responses when gathering information about
sensitive topics such as drug use, it is important to use the most optimal
method. OBJECTIVES: This study was carried out to address the impact of three
interview methods (street-based, household, and telephone interviews) on response
pattern to sensitive and non-sensitive questions in terms of participation,
disclosure and discontinuing rates. PATIENTS AND METHODS: We selected three
culturally diverse major cities of Iran. Then, we randomly selected 300 subjects,
100 for each type of interview, from each major city (899 in total). For street
based interviews only pedestrians who were walking alone were recruited, for
household interviews only one individual from each house participated (3-4 houses
in each alley were selected), and for telephone interviews we selected phone
numbers using a random number list. We asked five non-sensitive and five
sensitive (related to drug use and sexual contact among their personal network)
questions. RESULTS: For telephone and household interviews, relative to street
based interviews, participants were less likely to disclose alcohol and drug
related behaviors (Adjusted OR = 0.76; 95% CI: 0.60- 0.97) and sexual behaviors
among their network (Adjusted OR telephone/street-based = 0.64; 95% CI: 0.39-
1.07 and Adjusted OR household/ street-based = 0.56; 95% CI: 0.33- 0.95). We
found that participants who were interviewed via the telephone were more likely
(Adjusted OR = 1.24) and those who were interviewed at home were less likely
(Adjusted OR = 0.86) to report non-sensitive information compared to participants
who were interviewed on the street; however, these findings were not
statistically significant. The largest participation rate and the least
discontinuation rate were observed for household interviews. CONCLUSIONS: It
seems that the methods of interview effect response to both sensitive and non
sensitive questions. We believe that for street-based interviews, respondents may
disclose more sensitive information than telephone and household interviews.
PMID- 24349751
TI - Accuracy of estrogen and progesterone receptor assessment in core needle biopsy
specimens of breast cancer.
AB - BACKGROUND: Diagnosis of breast cancer is completed through core needle biopsy
(CNB) of the tumors but there is controversy on the accuracy of hormone receptor
results on CNB specimens. OBJECTIVES: We undertook this study to compare the
results of hormone receptor assessment in CNB and surgical samples on our
patients. PATIENTS AND METHODS: Hormone receptor status was determined in CNB and
surgical samples in breast cancer patients whose CNB and operation had been
performed in this institute from 2009 to 2011 and had not undergone neoadjuvant
chemotherapy. RESULTS: About 350 patients, 60 cases met all the criteria for
entering the study. The mean age was 49.8 years. Considering a confidence
interval (CI) of 95%, the sensitivity of ER and PR assessment in CNB was 92.9%
and 81%, respectively and the specificity of both was 100%. The Accuracy of CNB
was 98% for ER and 93% for PR. CONCLUSIONS: Our results confirm the acceptable
accuracy of ER assessment on CNB. The subject needs further investigation in
developing countries where omission of the test in surgical samples can be cost
and time-saving.
PMID- 24349752
TI - Preparedness of hospitals in north of iran to deal with disasters.
AB - INTRODUCTION: Preparedness of hospital has a major impact on their optimal and
satisfactory performance. This study aimed to investigate the preparedness of the
hospitals to deal with disasters. CASE PRESENTATION: This cross-sectional study
was carried in 2011 and all of the hospitals which were located in the northern
areas of Iran were investigated through the census method. The data collection
instruments were self-administered Managers' Awareness Questionnaire (40 items)
and a 141-item checklist. The mean percentage score of hospitals in management of
the unanticipated disasters program in the hospital was good. The mean score of
managers' awareness of the hospital status was moderate. With the increase in
managers' awareness, the preparedness of the hospitals significantly increased (r
= 0.73, P < 0.001). CONCLUSIONS: The findings showed the moderate preparedness of
the hospitals in the Northern provinces to deal with disasters.
PMID- 24349750
TI - Path analysis associations between perceived social support, stressful life
events and other psychosocial risk factors during pregnancy and preterm delivery.
AB - BACKGROUND: Although several socio-medical risk factors have been identified for
preterm labor, there is a gap in understanding the underlying etiology of preterm
labor. OBJECTIVES: The current study aimed to analyze the relationship pathway of
perceived social support, stressful life events, and other psychosocial risk
factors during pregnancy with incidence of preterm labor. MATERIALS AND METHODS:
In a prospective cohort study in four hospitals in Tehran, 500 pregnant women in
their 24th to 28th gestational weeks were studied. They filled out a self-report
questionnaire on perceived social support, depression, anxiety, stress and
stressful life events. Sociodemographic characteristics were also assessed. The
participants were followed up until labor, and the data about mother and the
newborn were collected after labor. The data were analyzed by SPSS 16 and Lisrel
8.8 software programs using pathway analysis. RESULTS: The final path model fit
well (CFI = 0.96; RMSEA = .064). The results showed that depression, anxiety, and
stress (beta = -0.18) directly, and stressful life events indirectly (beta=
0.0396) had the most predict on gestational age at labor. Perceived social
support, directly through socioeconomic status (beta=0.25), and indirectly
through stress, depression and anxiety (beta= -0.26) affected the gestational age
at birth (beta= 0.0468). CONCLUSIONS: The current study showed that supporting
pregnant mother moderates psychological problems such as stress, anxiety, and
depression, and hence reduces preterm labor.
PMID- 24349753
TI - Diastematomyelia Presenting With no Pain in a 53-Year-Old Man: A Case Report.
AB - Initial presentation of diastematomyelia is rarely seen in adults. The purpose of
this case report is to present a case of clinically silent diastematomyelia
unrecognized into adulthood and review of the literature. A 53-year-old Persian
man was admitted to our hospital with gait disturbance, weakness of the right
lower extremity, sensory loss of the left and right lower extremity of two weeks'
duration, with no pain or sphincter dysfunction. The patient underwent
radiological examinations, and diastematomyelia was diagnosed. The deteriorating
condition of our patient led to the decision to perform a surgery. A laminectomy
was performed from L-3 to L-5 with resection of the soft-tissue mass and excision
of the bony spur, and the patient was followed for 6 months. Postoperatively, the
patient did not show new neurologic deficit and he returned to work 4 months
after surgery. Our case was unique because of the absence of any pain, neurologic
signs, and precipitating acute event leading to diagnosis, until 53 years of age.
Surgical decompression of bony spur provided relative improvement of his
symptoms.
PMID- 24349754
TI - Lead poisoning-induced hypertensive crisis managed by prazosin: a case report.
AB - INTRODUCTION: Chronic lead exposure is known to be a risk factor for hypertension
(HTN). No specific medication is recommended for the treatment of lead-induced
hypertension (LIHTN). CASE PRESENTATION: Our patient was a male admitted with the
chief complaint of chronic abdominal pain. His whole blood lead level was
reported to be 1961 ug/L. He also mentioned a previous history of HTN managed by
propranolol (10 mg, TDS). He discharged himself by giving written consent and 19
days later, he was re-admitted due to high blood pressure of 220/140 mmHg. His
Blood pressure (BP) was decreased to 180/110 mmHg with sublingual captopril; but,
in maintenance therapy, higher doses of captopril could not further decrease BP.
Amlodipine was tried which was discontinued due to the patient intolerance.
Prazosin was then administered in gradual increasing doses up to 1 mg twice a day
and captopril was tapered. CONCLUSIONS: We would like to suggest that LIHTN may
better be managed by alpha blockers compared with converting enzyme inhibitors.
PMID- 24349755
TI - Atypical giant hydatid cyst at the thoracic wall causing bone and soft tissue
destruction: report of a case.
AB - Hydatid cyst is a zoonotic disease that is common in the Mediterranean region.
Thoracic wall, rib or extrapulmonary intrathoracic localization of the cysts is
very rare. Giant extrapulmonary intrathoracic hydatid cysts can lead to both
diagnostic and treatment difficulties and can be confused with tumor. We present
a case of a hydatid cyst with thoracic wall involvement mimicking tumor. We
confirmed diagnosis only by surgical exploration and histopathological
examination because radiology is not conclusive .Surgical treatment involved the
total extirpation of cyst together wide debridement and resection of affected
tissue. Primary thoracic wall closures were performed. In thoracic wall
localization of cyst, post-operative course of albendazole for 6 weeks associated
with surgery can help in sterilizing the cyst and reduce the recurrence rate. In
this article, we presented a thoracic wall hydatidosis which is very uncommon
asymptomatic presentation of hydatid cyst disease with its surgical management.
PMID- 24349756
TI - Clinical learning environment at shiraz medical school in the educators' and
residents' viewpoints.
PMID- 24349757
TI - Ipsilateral traumatic fractures of the proximal and distal parts of the humerus
(floating arm) with fracture of distal clavicle: a case report.
PMID- 24349759
TI - Should External Powered Orthoses be Used by Paraplegic Subjects or Not?
PMID- 24349758
TI - Genotyping of acanthamoeba isolated from surface and stagnant waters of qazvin,
central iran.
PMID- 24349760
TI - A method for biomarker directed survival prediction in advanced non-small-cell
lung cancer patients treated with Carboplatin-based therapy.
AB - Platinum-based chemotherapy is a primary treatment of choice for advanced non
small-cell lung cancer (NSCLC). Analytical methods to specifically evaluate
biomarkers predictive of therapeutic efficacy have not been developed. Two
randomized phase III trials of carboplatin-based chemotherapy in advanced NSCLC
were used for learning and validating the predictive value of ERCC1 in situ
protein levels, as measured by accurate quantitative analysis (AQUA). A novel
Bayesian method was applied to identify the outcome-based threshold in the
learning trial only. Overall survival (OS) was assessed by Kaplan-Meier analysis
with log rank testing to determine statistical significance in the validating
trial. For patients treated with gemcitabine and carboplatin, the median OS was
9.5 months (95% CI 6.7 to 11.8) for the high ERCC1 group compared to 15.6 months
(95% CI 11.6 to 24.8) for the low ERCC1 group in the validation trial (log rank p
value = 0.007). The hazard ratio for low ERCC1 was 0.598 (95% CI, 0.394 to 0.908;
p = 0.016) relative to high ERCC1 adjusted for age, sex, and histology.
CONCLUSIONS: Patients with advanced NSCLC could be stratified into high and low
ERCC1 expression groups. Patients with low levels benefited from platinum-based
chemotherapy, whereas those with high levels did not.
PMID- 24349761
TI - Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging
Techniques.
AB - Burkholderia mallei, the etiologic agent of glanders, are Category B select
agents with biothreat potential, and yet effective therapeutic treatments are
lacking. In this study, we showed that CpG administration increased survival,
demonstrating protection in the murine glanders model. Bacterial recovery from
infected lungs, liver and spleen was significantly reduced in CpG-treated animals
as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected
animals were infiltrated with higher levels of neutrophils and inflammatory
monocytes, as compared to control animals. Employing the B. mallei bioluminescent
strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial
dissemination and neutrophil trafficking were monitored in real-time using
multimodal in vivo whole body imaging techniques. CpG-treatment increased
recruitment of neutrophils to the lungs and reduced bioluminescent bacteria,
correlating with decreased bacterial burden and increased protection against
acute murine glanders. Our results indicate that protection of CpG-treated
animals was associated with recruitment of neutrophils prior to infection and
demonstrated, for the first time, simultaneous real time in vivo imaging of
neutrophils and bacteria. This study provides experimental evidence supporting
the importance of incorporating optimized in vivo imaging methods to monitor
disease progression and to evaluate the efficacy of therapeutic treatment during
bacterial infections.
PMID- 24349762
TI - Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in
Chronically Stressed Rat Dams.
AB - Exposure of mothers to chronic stressors during pregnancy or the postpartum
period often leads to the development of depression, anxiety, or other related
mood disorders. The adverse effects of mood disorders are often mediated through
maternal behavior and recent work has identified arginine vasopressin (AVP) as a
key neuropeptide hormone in the expression of maternal behavior in both rats and
humans. Using an established rodent model that elicits behavioral and
physiological responses similar to human mood disorders, this study tested the
effectiveness of chronic AVP infusion as a novel treatment for the adverse
effects of exposure to chronic social stress during lactation in rats. During
early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased
the latency to initiate nursing and time spent retrieving pups, and increased pup
grooming and total maternal care (sum of pup grooming and nursing). AVP treatment
was also effective in decreasing maternal aggression and the average duration of
aggressive bouts on day 3 of lactation. Central AVP may be an effective target
for the development of treatments for enhancing maternal behavior in individuals
exposed to chronic social stress.
PMID- 24349763
TI - Systems Biology Profiling of AMD on the Basis of Gene Expression.
AB - Genetic pathways underlying the initiation and progression of age-related macular
degeneration (AMD) have not been yet sufficiently revealed, and the correlations
of AMD's genotypes, phenotypes, and disease spectrum are still awaiting
resolution. We are tackling both problems with systems biology phylogenetic
parsimony analysis. Gene expression data (GSE29801: NCBI, Geo) of macular and
extramacular specimens of the retinas and retinal pigment epithelium (RPE)
choroid complexes representing dry AMD without geographic atrophy (GA), choroidal
neovascularization (CNV), GA, as well as pre-AMD and subclinical pre-AMD were
polarized against their respective normal specimens and then processed through
the parsimony program MIX to produce phylogenetic cladograms. Gene lists from
cladograms' nodes were processed in Genomatix GePS to reveal the affected
signaling pathway networks. Cladograms exposed a highly heterogeneous
transcriptomic profiles within all the conventional phenotypes. Moreover, clades
and nodal synapomorphies did not support the classical AMD phenotypes as valid
transcriptomal genotypes. Gene lists defined by cladogram nodes showed that the
AMD-related deregulations occurring in the neural retina were different from
those in RPE-choroidal tissue. Our analysis suggests a more complex
transcriptional profile of the phenotypes than expected. Evaluation of the
disease in much earlier stages is needed to elucidate the initial events of AMD.
PMID- 24349765
TI - Hemodynamic correlates of late systolic flow velocity augmentation in the carotid
artery.
AB - Background. The contour of the common carotid artery (CCA) blood flow velocity
waveform changes with age; CCA flow velocity increases during late systole, and
this may contribute to cerebrovascular disease. Late systolic flow velocity
augmentation can be quantified using the flow augmentation index (FAIx). We
examined hemodynamic correlates of FAIx to gain insight into determinants of CCA
flow patterns. Methods. CCA Doppler ultrasound and wave intensity analysis (WIA)
were used to assess regional hemodynamics in 18 young healthy men (age 22 +/- 1
years). Forward waves (W 1) and backward waves (negative area, NA) were measured
and used to calculate the reflection index (NA/W 1 = RIx). Additional parameters
included W 2 which is a forward travelling expansion/decompression wave of
myocardial origin that produces suction, CCA single-point pulse wave velocity
(PWV) as a measure of arterial stiffness, and CCA pressure augmentation index
(AIx). Results. Primary correlates of FAIx included W 2 (r = - 0.52, P < 0.05),
logRIx (r = 0.56, P < 0.05), and AIx (r = 0.60, P < 0.05). FAIx was not
associated with CCA stiffness (P > 0.05). Conclusions. FAIx is a complex
ventricular-vascular coupling parameter that is associated with both increased
expansion wave magnitude (increased suction from the left ventricle) and
increased pressure from wave reflections.
PMID- 24349764
TI - Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion:
A Perspective.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive and lethal disease of motor
neuron degeneration, leading to paralysis of voluntary muscles and death by
respiratory failure within five years of onset. Frontotemporal dementia (FTD) is
characterised by degeneration of frontal and temporal lobes, leading to changes
in personality, behaviour, and language, culminating in death within 5-10 years.
Both of these diseases form a clinical, pathological, and genetic continuum of
diseases, and this link has become clearer recently with the discovery of a
hexanucleotide repeat expansion in the C9orf72 gene that causes the FTD/ALS
spectrum, that is, c9FTD/ALS. Two basic mechanisms have been proposed as being
potentially responsible for c9FTD/ALS: loss-of-function of the protein encoded by
this gene (associated with aberrant DNA methylation) and gain of function through
the formation of RNA foci or protein aggregates. These diseases currently lack
any cure or effective treatment. Antisense oligonucleotides (ASOs) are modified
nucleic acids that are able to silence targeted mRNAs or perform splice
modulation, and the fact that they have proved efficient in repeat expansion
diseases including myotonic dystrophy type 1 makes them ideal candidates for
c9FTD/ALS therapy. Here, we discuss potential mechanisms and challenges for
developing oligonucleotide-based therapy for c9FTD/ALS.
PMID- 24349767
TI - Intersection of HIV and Reproductive Health.
PMID- 24349766
TI - Preliminary blood pressure screening in a representative sample of extremely
obese Kuwaiti adolescents.
AB - A relationship between blood pressure (BP) and obesity has been found in young
adults, but no data are available for adolescents in Kuwait. 257 adolescent (11
19 years) participants were categorized into two groups according to their BMI;
48 nonobese (21 males: 43.7% and 27 females: 56.3%) with mean age of 15.61 +/-
2.40 years and 209 obese (128 males: 61.25% and 81 females: 38.75%) with mean age
of 15.02 +/- 2.82 years. The mean BMI was 21.7 +/- 2.23 kg/m(2) for the nonobese
group and 34.47 +/- 4.70 kg/m(3) for the obese group. Most BP measures based on a
single screening were significantly higher in the obese group. The prevalence of
elevated BP was significantly higher in the obese subjects (nonobese: 13%; obese:
63%; P < 0.0001). In the obese group, there was a significant positive
correlation between total sample BMI and all BP measures except the pulse
pressure. There was a similar rate of elevated blood pressure between males and
females (64% versus 60%; P = 0.66). For both isolated systolic elevated BP and
isolated diastolic elevated BP, the prevalences were comparable between the males
(systolic: 42%; diastolic: 5%) and females (systolic: 34%; diastolic: 14%). Only
systolic BP was positively correlated with BMI in obese adolescent males
(Spearman r = 0.18; P < 0.05), with a significant correlation between BMI with
diastolic (Spearman r = 0.22; P < 0.05) and mean BP (Spearman r = 0.21; P < 0.05)
in females.
PMID- 24349768
TI - Diagnosis of severe fetal anemia based on perinatal outcomes: a comparative
analysis of the current reference values.
AB - Objectives. To compare current criteria for severe fetal anemia diagnosis.
Methodology. A cohort study analyzed 105 alloimmunized fetuses that underwent
cordocentesis due to risk of anemia. Concordance among the diagnostic criteria
for severe fetal anemia, hemoglobin deficit >7 g/dL, hemoglobin deficit >=5 g/dL,
and hemoglobin concentration <0.55 MoM, was analyzed using Cohen's Kappa index.
Perinatal mortality, fetal hydrops, and fetal acidosis were used to discuss
discordances. Results. There was fair concordance among the three criteria
analyzed: 0.80 (Kappa index, IC 95%: 0.67 to 0.93) when comparing hemoglobin
deficit >7.0 g/dL and hemoglobin concentration <0.55 MoM criteria, 0.63 (Kappa
index, IC 95%: 0.47 to 0.69) when comparing hemoglobin deficit >=5.0 g/dL and
hemoglobin deficit >7.0 g/dL reference, and 0.77 (Kappa index, IC 95%: 0.64 to
0.90) when comparing hemoglobin deficit>=5.0 g/dL and hemoglobin concentration
<0.55 MoM standards. Eighteen cases were classified differently depending on the
criteria used. The cut-off point of hemoglobin deficit >=5 g/dL was the best
criterion to discriminate fetuses with poor perinatal outcome in our study.
Conclusions. Relevant discordances in classification of severe fetal anemia were
pointed out. Some criteria may underestimate the real gravity of fetal anemia.
PMID- 24349769
TI - The effect of short-term aerobic exercise on depression and body image in Iranian
women.
AB - The purpose of this study was to determine the effect of short-term aerobic
exercise on depression symptoms and body image attitudes among Iranian women. In
this quasiexperimental study, 82 females were assigned to experimental group
(aerobic exercise group, n = 41) or control group (waiting list, n = 41) and
evaluated by Beck Depression Inventory-second edition (BDI-II) and
Multidimensional Body Self-Relation Questionnaire (MBSRQ), respectively. The
experimental group received four-week aerobic exercise program, and control group
had been asked to wait for the next four weeks. Results of this study confirmed
the significant decrease in depression symptoms at the experimental group
compared to control group (P < 0.5). For the body image dependent variables,
significant improvement was also found in appearance evaluation, appearance
orientation, health orientation, and illness orientation in aerobic exercise
group (P < 0.5).
PMID- 24349770
TI - Know your client and know your team: a complexity inspired approach to
understanding safe transitions in care.
AB - Background. Transitions in care are one of the most important and challenging
client safety issues in healthcare. This project was undertaken to gain insight
into the practice setting realities for nurses and other health care providers as
they manage increasingly complex care transitions across multiple settings.
Methods. The Appreciative Inquiry approach was used to guide interviews with
sixty-six healthcare providers from a variety of practice settings. Data was
collected on participants' experience of exceptional care transitions and
opportunities for improving care transitions. Results. Nurses and other
healthcare providers need to know three things to ensure safe care transitions:
(1) know your client; (2) know your team on both sides of the transfer; and (3)
know the resources your client needs and how to get them. Three themes describe
successful care transitions, including flexible structures; independence and
teamwork; and client and provider focus. Conclusion. Nurses often operate at the
margins of acceptable performance, and flexibility with regulation and standards
is often required in complex sociotechnical work like care transitions. Priority
needs to be given to creating conditions where nurses and other healthcare
providers are free to creatively engage and respond in ways that will optimize
safe care transitions.
PMID- 24349771
TI - Participation in decision making as a property of complex adaptive systems:
developing and testing a measure.
AB - Objectives. To (1) describe participation in decision-making as a systems-level
property of complex adaptive systems and (2) present empirical evidence of
reliability and validity of a corresponding measure. Method. Study 1 was a mail
survey of a single respondent (administrators or directors of nursing) in each of
197 nursing homes. Study 2 was a field study using random, proportionally
stratified sampling procedure that included 195 organizations with 3,968
respondents. Analysis. In Study 1, we analyzed the data to reduce the number of
scale items and establish initial reliability and validity. In Study 2, we
strengthened the psychometric test using a large sample. Results. Results
demonstrated validity and reliability of the participation in decision-making
instrument (PDMI) while measuring participation of workers in two distinct job
categories (RNs and CNAs). We established reliability at the organizational level
aggregated items scores. We established validity of the multidimensional
properties using convergent and discriminant validity and confirmatory factor
analysis. Conclusions. Participation in decision making, when modeled as a
systems-level property of organization, has multiple dimensions and is more
complex than is being traditionally measured. Managers can use this model to form
decision teams that maximize the depth and breadth of expertise needed and to
foster connection among them.
PMID- 24349772
TI - Self-care and chronic disease.
PMID- 24349773
TI - A systematic review of the utility of residual vein obstruction studies in
primary and secondary venous thrombosis.
AB - Background. Residual vein obstruction (RVO), the persistence of venous thrombosis
with time and often after anticoagulation, may indicate a systemic prothrombotic
condition. Prior studies have shown varying efficacy in using RVO as a risk
factor for future venous thromboembolic (VTE) recurrence. Methods. To assess
whether positive RVO imaging predicts recurrent VTE events, we performed a meta
analysis on studies in which patients with documented VTEs, anticoagulated for a
minimum of 4 weeks, had repeat sonography to assess RVO and were subsequently
followed for recurrent events. Results. Thirteen studies met inclusion criteria:
3531 patient VTE events with 3474 evaluable results were analyzed. The presence
of RVO was associated with recurrence in all VTE (OR 1.93; 95% CI: 1.29, 2.89)
and secondary VTE (OR 2.78; 95% CI: 1.41, 5.5) but not for primary VTE (OR 1.35;
95% CI: 0.87, 2.08). When cancer patients were eliminated from the secondary VTE
group, there was no longer a significant association of RVO with VTE recurrence
(OR 1.73; 95% CI: 0.81, 3.67) while in the subset of cancer patients, presence of
RVO was associated with an increase in VTE recurrence risk (OR 5.14; 95% CI:
1.59, 16.65, P < 0.006). Conclusions. We conclude that the presence of RVO is
associated with recurrence in secondary VTE but not in primary VTE and that
association may be driven by the subset with cancer.
PMID- 24349774
TI - Use of oral anticoagulation therapy in atrial fibrillation after stroke: results
from a nationwide registry.
AB - Background. The knowledge is still sparse about patient related factors,
influencing oral anticoagulation therapy (OAC) rates, in stroke patients with
atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke
patients diagnosed with AF and to identify patient related factors influencing
the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we
identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011.
Frequency analysis was used to assess the use of OAC in patients with AF, and
logistic regression was used to determine independent predictors of OAC. Results.
17.1% (n = 9,482) of ischemic stroke patients had AF. OAC prescription rates were
increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication,
and 3.7% were not prescribed OAC without a stated contraindication. Younger age,
less severe stroke, and male gender were positive predictors of OAC, while
excessive alcohol consumption, smoking, and institutionalization were negative
predictors of OAC (P values < 0.05). Conclusions. Advanced age, severe stroke,
female gender, institutionalization, smoking, and excessive alcohol consumption
were associated with lower OAC rates. Contraindications were generally present in
patients not in therapy, and the assumed underuse of OAC may be overestimated.
PMID- 24349775
TI - Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with
Newly Diagnosed Tuberculosis in Virginia, USA.
AB - Slow responders to tuberculosis (TB) treatment in Virginia have prolonged
treatment duration and consume more programmatic resources. Diabetes is an
independent risk factor for slow response and low serum anti-TB drug
concentrations. Thus, a statewide initiative of early therapeutic drug monitoring
(TDM) for isoniazid and rifampin at 2 weeks after TB treatment was piloted for
all diabetics with newly diagnosed TB. During the period of early TDM, 12/01/2011
12/31/2012, 21 diabetics had C 2 hr concentrations performed and 16 (76%) had a
value below the expected range for isoniazid, rifampin, or both. Fifteen had
follow-up concentrations after dose adjustment and 12 (80%) increased to within
the expected range (including all for rifampin). Of 16 diabetic patients with
pulmonary TB that had early TDM, 14 (88%) converted their sputum culture to
negative in <2 months. Early TDM for diabetics was operationally feasible, may
speed response to TB therapy, and can be considered for TB programs with high
diabetes prevalence.
PMID- 24349776
TI - The immediate effects of orthoses on pain in people with lateral epicondylalgia.
AB - Objective. Tennis elbow is a common cause of upper limb dysfunction and a primary
reason for pain at the lateral aspect of the elbow. The purpose of this study was
to investigate the effects of three commonly used orthoses on pain severity. An
elbow band, an elbow sleeve, and a wrist splint were assessed for their ability
to reduce the level of reported pain. Method. A crossover randomized controlled
trial was used. The orthoses were worn in a randomized order, and all
participants were required to complete a control trial for which they wore a
placebo orthosis. 52 participants with lateral epicondylalgia were recruited, and
the level of pain at their elbow was recorded using the visual analogue scale
(VAS). Results. The reported pain for all orthoses was lower than that of the
placebo (P < 0.05). Pain reduction was significantly greater with a counterforce
elbow band or a counterforce elbow sleeve compared to a wrist splint (P < 0.01).
There was no significant difference between a counterforce elbow band and a
counterforce elbow sleeve (P = 0.23). Conclusion. All the types of orthoses
studied showed an immediate improvement on pain severity in people with lateral
epicondylalgia. The counterforce elbow orthoses (elbow band and elbow sleeve)
presented the greatest improvement, suggesting that either of them can be used as
a first treatment choice to alleviate the pain in people with tennis elbow.
PMID- 24349777
TI - Is There a Relation between Tension-Type Headache, Temporomandibular Disorders
and Sleep?
AB - Introduction. Tension-Type Headache (TTH) is the most prevalent headache often
associated with impaired function and quality of life. Temporomandibular
Disorders (TMD) and TTH frequently coexist; characterized by pericranial
tenderness and impact on daily life. We aim to apply a standardized questionnaire
for TMD to characterize and analyse an eventual relation between sleep and oral
health in TTH in a controlled design. Material and Methods. 58 consecutive TTH
patients and 58 healthy controls were included. The Research Diagnostic Criteria
for Temporomandibular Disorders (RDC/TMD) questionnaire, Oral Health Impact
profile (OHIP) and questionnaires for sleep were applied. Results. TTH-patients
had significantly higher pain scores (P < 0.001), decreased quality of life (P <
0.001), and higher total sleep scores (P < 0.001) compared to controls.
Conclusion. For the first time we have identified a clear relation between TTH
and TMD symptoms, depression, anxiety, poor sleep, and impairments of oral
function in carefully classified patients. These findings indicate a close, but
incomplete, overlap between TTH and TMD. Their underlying pathophysiological
mechanisms need further research.
PMID- 24349778
TI - Vest Chest Physiotherapy Airway Clearance is Associated with Nitric Oxide
Metabolism.
AB - Background. Vest chest physiotherapy (VCPT) enhances airway clearance in cystic
fibrosis (CF) by an unknown mechanism. Because cilia are sensitive to nitric
oxide (NO), we hypothesized that VCPT enhances clearance by changing NO
metabolism. Methods. Both normal subjects and stable CF subjects had pre- and
post-VCPT airway clearance assessed using nasal saccharin transit time (NSTT)
followed by a collection of exhaled breath condensate (EBC) analyzed for NO
metabolites (NO x ). Results. VCPT shorted NSTT by 35% in normal and stable CF
subjects with no difference observed between the groups. EBC NO x concentrations
decreased 68% in control subjects after VCPT (before = 115 +/- 32 MU M versus
after = 37 +/- 17 MU M; P < 0.002). CF subjects had a trend toward lower EBC NO
x . Conclusion. We found an association between VCPT-stimulated clearance and
exhaled NO x levels in human subjects. We speculate that VCPT stimulates
clearance via increased NO metabolism.
PMID- 24349779
TI - Danish General Practitioners' Use of Prostate-Specific Antigen in Opportunistic
Screening for Prostate Cancer: A Survey Comprising 174 GPs.
AB - Background. The use of prostate-specific antigen test has markedly increased in
Danish general practice in the last decade. Despite the national guidelines
advice against PSA screening, opportunistic screening is supposed to be the
primary reason for this increased number of PSA tests performed. Aims. Based on
the increase in the amount of PSA conducted, we aimed to analyse how GPs in
Denmark use the PSA test. Methods. A self-administrated questionnaire concerning
symptomatic and asymptomatic patient cases was developed based on the national
and international guidelines and the extensive literature review, and an in-depth
interview conducted with a GP was performed. Results. None of the GPs would do a
PSA measurement for an asymptomatic 76-year-old man. For asymptomatic 55- and 42
year-old men, respectively, 21.9% and 18.6% of GPs would measure PSA. Patient
request and concern could be potential reasons for measuring PSA for asymptomatic
patients. Almost all GPs stated that a PSA measurement is indicated for
symptomatic 49- and 78-year-old men, respectively, 98.9% and 93.8%. Conclusion.
Opportunistic PC screening is being performed in general practice to a high
degree. Hence, current guidelines are not followed, and intense focus should be
on more effective implementation strategies in order to avoid overuse of PSA.
PMID- 24349780
TI - Long-Term Use of Probiotic-Containing Yogurts Is a Safe Way to Prevent
Helicobacter pylori: Based on a Mongolian Gerbil's Model.
AB - Background. The suppression of Helicobacter pylori (H. pylori) decreases H.
pylori-related diseases. The probiotics have an inhibitory effect on H. pylori.
Aim. We investigated the effects of long-term use of yogurt on H. pylori based on
Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement
of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six
gerbils were divided into five groups. All groups were inoculated with H. pylori
for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th
week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from
5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was
evaluated according to the Sydney system. Results. The positive rates of H.
pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E).
Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal
metaplasia. Gr. D showed higher IL-10 and lower TNF- alpha expression than Gr. E.
Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The
long-term use of yogurt would be an alternative strategy to manage H. pylori
infection.
PMID- 24349781
TI - Effects of maternal factors on birth weight in Japan.
AB - OBJECTIVE: We investigated the possible factors related to the birth weight (BW)
using the Japanese perinatal database. METHODS: The live infants born at 37 to 41
weeks of gestation were enrolled in this study. Cases with diabetic pregnancy,
preeclampsia, an anomalous fetus, and a fetus with chromosomal abnormalities were
excluded. A multiple regression analysis for confounding factors and an analysis
of covariance (ANCOVA) for comparing the BW in 2006 and 2010 were used for the
statistical analysis. RESULTS: The BW significantly decreased from 2950.8 g in
2006 (n = 27,723) to 2937.5 g in 2010 (n = 38,008) in the overall population, and
this decrease was similar for male and female neonates. All confounding factors,
except for the mode of delivery, affected the BW. Primiparity, smoking, and a
female gender were related to the decrease in BW, whereas maternal age, maternal
height, weight gain during pregnancy, BMI, the use of in vitro fertilization,
induction of labor, and gestational duration were related to an increased BW. The
ANCOVA showed that no significant change of the BW was seen between 2006 and 2010
(the difference was 2.164 g, P = 0.414). CONCLUSION: The gestational duration is
the most important factor affecting the BW in singleton term infants.
PMID- 24349783
TI - Retracted: the effects of fetal gender on serum human chorionic gonadotropin and
testosterone in normotensive and preeclamptic pregnancies.
PMID- 24349782
TI - Effect of folic acid supplementation in pregnancy on preeclampsia: the folic acid
clinical trial study.
AB - Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy
and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation
in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to
recruit 3,656 high risk women to evaluate a new prevention strategy for PE:
supplementation of folic acid throughout pregnancy. Pregnant women with increased
risk of developing PE presenting to a trial participating center between 8(0/7)
and 16(6/7) weeks of gestation are randomized in a 1 : 1 ratio to folic acid 4.0
mg or placebo after written consent is obtained. Intent-to-treat population will
be analyzed. The FACT study was funded by the Canadian Institutes of Health
Research in 2009, and regulatory approval from Health Canada was obtained in
2010. A web-based randomization system and electronic data collection system
provide the platform for participating centers to randomize their eligible
participants and enter data in real time. To date we have twenty participating
Canadian centers, of which eighteen are actively recruiting, and seven
participating Australian centers, of which two are actively recruiting.
Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States
is expected to begin by the second or third quarter of 2013. This trial is
registered with NCT01355159.
PMID- 24349784
TI - The effect of cesarean delivery skin incision approach in morbidly obese women on
the rate of classical hysterotomy.
AB - OBJECTIVE: To assess the risk of classical hysterotomy and surgical morbidity
among women with a body mass index (BMI) greater than 40 kg/m2 who underwent a
supraumbilical incision at the time of cesarean delivery. METHODS: We conducted a
retrospective cohort study in women having a BMI greater than 40 kg/m2 who
underwent a cesarean delivery of a live, singleton pregnancy from 2007 to 2011 at
a single tertiary care institution. Intraoperative and postoperative outcomes
were compared between patients undergoing supraumbilical vertical (cohort, n =
45) or Pfannenstiel (controls, n = 90) skin incisions. RESULTS: Women undergoing
supraumbilical incisions had a higher risk of classical hysterotomy (OR, 24.6;
95% CI, 9.0-66.8), surgical drain placement (OR, 6.5; 95% CI, 2.6-16.2),
estimated blood loss greater than 1 liter (OR, 3.4; 95% CI, 1.4-8.4), and longer
operative time (97 +/- 38 minutes versus 68 +/- 30 minutes; P < .001) when
compared to subjects with Pfannenstiel incisions (controls). There was no
difference in the risk of wound complication between women undergoing
supraumbilical or Pfannenstiel incisions (OR, 2.7; 95% CI, 0.9-8.0). CONCLUSION:
In women with a BMI above 40 kg/m2, supraumbilical incision at the time of
cesarean delivery is associated with a greater risk of classical hysterotomy and
operative morbidity.
PMID- 24349785
TI - The Anatomical Correlation between the Internal Venous Vertebral System and the
Cranial Venae Cavae in Rabbit.
AB - The aim of this study was to describe the possible variations in the connection
between the internal venous vertebral system and the cranial vena cava in rabbit
using corrosion technique. The study was carried out on 40 adult New Zealand
white rabbits. The venous system was injected by using Batson's corrosion casting
kit number 17. We found the connection between the internal venous vertebral
system and the cranial vena cava by means of the vertebral veins and the right
azygos vein. The vertebral vein was present as independent tributary in 36 cases
(90%). In the rest of the cases, it was found as being double, being triple, or
forming a common trunk with other veins. The azygos vein was present as
independent tributary of the cranial vena cava in 39 cases (97.5%). We found also
a common trunk formed by the junction of the deep cervical vein, the right
vertebral vein, and the azygos vein in one case (2.5%). The azygos vein received
6, 7, 8, or 9 pairs of dorsal intercostal veins. Documenting the anatomical
variations in the rabbit will aid in the planning of future experimental studies
and determining the clinical relevance on such studies.
PMID- 24349786
TI - What is New and Innovative in Emergency Neurosurgery? Emerging Diagnostic
Technologies Provide Better Care and Influence Outcome: A Specialist Review.
AB - The development of emergency medical services and especially neurosurgical
emergencies during recent decades has necessitated the development of novel
tools. Although the gadgets that the neurosurgeon uses today in emergencies give
him important help in diagnosis and treatment, we still need new technology,
which has rapidly developed. This review presents the latest diagnostic tools,
which offer precious help in everyday emergency neurosurgery practice. New
ultrasound devices make the diagnosis of haematomas easier. In stroke, the
introduction of noninvasive new gadgets aims to provide better treatment to the
patient. Finally, the entire development of computed tomography and progress in
radiology have resulted in innovative CT scans and angiographic devices that
advance the diagnosis, treatment, and outcome of the patent. The pressure on
physicians to be quick and effective and to avoid any misjudgement of the patient
has been transferred to the technology, with the emphasis on developing new
systems that will provide our patients with a better outcome and quality of life.
PMID- 24349787
TI - Roles of motorcycle type and protective clothing in motorcycle crash injuries.
AB - Background. The aims of this study were to identify subgroups of motorcyclists
with a higher accident risk and evaluate the efficiency of protective clothing
for preventing injuries. Methods. A 1-year prospective study of motorcycle
crashes was conducted beginning in June 2012. Participants were patients involved
in motorcycle crashes and admitted to our emergency department. Results. A total
of 226 patients were included in the study. In total, 174 patients were involved
in crashes with light motorcycles. Patients involved in a motorcycle accident
without a helmet had a higher incidence of head and maxillofacial trauma.
Motorcycle jackets were not protective for systemic injuries (P > 0.05) or upper
extremity fractures (P > 0.05). Motorcycle pants (P > 0.05) and motorcycle shoes
(P > 0.05) were not protective against leg and foot fractures. However,
motorcycle protective clothes were protective against soft-tissue injuries (P =
0.001). Conclusion. Riders of heavy motorcycles rode more safely than riders of
light motorcycles. Light motorcycle riders were the most vulnerable and comprised
the largest percentage of motorcyclists. Helmets may be effective for preventing
head and facial injuries. Other protective clothes were not effective against
fractures or systemic injuries.
PMID- 24349788
TI - 3D versus 2D Systematic Transrectal Ultrasound-Guided Prostate Biopsy: Higher
Cancer Detection Rate in Clinical Practice.
AB - Objectives. To compare prostate cancer detection rates of extended 2D versus 3D
biopsies and to further assess the clinical impact of this method in day-to-day
practice. Methods. We analyzed the data of a cohort of 220 consecutive patients
with no prior history of prostate cancer who underwent an initial prostate biopsy
in daily practice due to an abnormal PSA and/or DRE using, respectively, the
classical 2D and the new 3D systems. All the biopsies were done by a single
experienced operator using the same standardized protocol. Results. There was no
significant difference in terms of age, total PSA, or prostate volume between the
two groups. However, cancer detection rate was significantly higher using the 3D
versus the 2D system, 50% versus 34% (P < 0.05). There was no statistically
significant difference while comparing the 2 groups in term of nonsignificant
cancer detection. Conclusion. There is reasonable evidence demonstrating the
superiority of the 3D-guided biopsies in detecting prostate cancers that would
have been missed using the 2D extended protocol.
PMID- 24349789
TI - Immunopathogenic Role of Herpes Simplex Virus in Behcet's Disease.
AB - The role of viral infections, such as herpes simplex virus (HSV) infection, in
the pathogenesis of Behcet's disease (BD) has been investigated for many years.
HSV has been detected in peripheral blood leukocytes, saliva, and genital ulcers
of patients with BD. Various cell adhesion molecules on cultured endothelial
cells have been induced by HSV in a TNF- alpha dependent manner. In addition, a
BD-like animal model was developed by inoculating ICR mouse earlobes with HSV,
and antiviral treatment was effective in improving BD-like symptoms in this
model. Still, there are several incompletely characterized proteins that possess
antiviral properties and are being investigated as mediators of viral infection
related chronic inflammatory reactions. Although the role of HSV in the
pathogenesis of BD remains to be fully established, recent research findings
regarding HSV in BD have expanded our understanding of the disease and will
hopefully lead to the development of more effective therapeutic agents in the
near future.
PMID- 24349790
TI - Staging Investigations in Breast Cancer: Collective Opinion of UK Breast
Surgeons.
AB - Introduction. Certain clinicopathological factors are associated with a higher
likelihood of distant metastases in primary breast cancer. However, there remains
inconsistency in which patients undergo formal staging for distant metastasis and
the most appropriate investigation(s). Aims. To identify UK surgeon preferences
and practice with regard to staging investigations for distant metastases.
Methods. A survey was disseminated to members of the Association of Breast
Surgery by e-mail regarding surgeon/breast unit demographics, use of staging
investigations, and local policy on pre/postoperative staging investigations.
Several patient scenarios were also presented. Results. 123 of 474 (25.9%)
recipients completed the survey. Investigations routinely employed for patients
diagnosed with early breast cancer included serological/haematological tests (72%
respondents), axillary ultrasound (67%), liver ultrasound (2%), chest radiograph
(36%), and computed tomography (CT) (1%). Three areas contributed to decisions to
undertake staging by CT scan: tumour size, axillary nodal status, and plan for
chemotherapy. There was widespread variation as to criteria for CT staging based
on tumour size and nodal status, as well as the choice of staging investigation
for the clinical scenarios presented. Conclusions. There remains variation in the
use of staging investigations for distant disease in early breastcancer despite
available guidelines.
PMID- 24349791
TI - Metastatic lesions to the liver.
PMID- 24349792
TI - Distal Femur Allograft Prosthetic Composite Reconstruction for Short Proximal
Femur Segments following Tumor Resection.
AB - Short metaphyseal segments remaining after distal femoral tumor resection pose a
unique challenge. Limb sparing options include a short stemmed modular
prosthesis, total endoprosthetic replacement, cross-pin fixation to a custom
implant, and allograft prosthetic composite reconstruction (APC). A series of
patients with APC reconstruction were evaluated to determine functional and
radiologic outcome and complication rates. Twelve patients were retrospectively
identified who had a distal femoral APC reconstruction between 1994 and 2007 to
salvage an extremity with a segment of remaining bone that was less than 20
centimeters in length. Seventeen APC reconstructions were performed in twelve
patients. Eight were primary procedures and nine were revision procedures.
Average f/u was 89 months. Twelve APC reconstructions (71%) united and five (29%)
were persistent nonunions. At most recent followup 10 patients (83%) had a healed
APC which allowed WBAT. One pt (8%) had an amputation and one pt (8%) died prior
to union. Average time to union was 19 months. Four pts (33%) or five APC
reconstructions (29%) required further surgery to obtain a united reconstruction.
Although Distal Femoral APC reconstruction has a high complication rate, a stable
reconstruction was obtained in 83% of patients.
PMID- 24349793
TI - A preliminary evaluation of the physiological mechanisms of action for sleep
restriction therapy.
AB - Our objective was to investigate the physiological mechanisms involved in the
sleep restriction treatment of insomnia. A multiple baseline across subjects
design was used. Sleep of five participants suffering from insomnia was assessed
throughout the experimentation by sleep diaries and actigraphy. Ten nights of
polysomnography were conducted over five occasions. The first two-night
assessment served to screen for sleep disorders and to establish a baseline for
dependent measures. Three assessments were undertaken across the treatment
interval, with the fifth and last one coming at follow-up. Daily cortisol assays
were obtained. Sleep restriction therapy was applied in-lab for the first two
nights of treatment and was subsequently supervised weekly. Interrupted time
series analyses were computed on sleep diary data and showed a significantly
decreased wake time, increased sleep efficiency, and decreased total sleep time.
Sleepiness at night seems positively related to sleep variables, polysomnography
data suggest objective changes mainly for stage 2, and power spectral analysis
shows a decrease in beta-1 and -2 powers for the second night of treatment.
Cortisol levels seem to be lower during treatment. These preliminary results
confirm part of the proposed physiological mechanisms and suggest that sleep
restriction contributes to a rapid decrease in hyperarousal insomnia.
PMID- 24349794
TI - The cytology, isozyme, HPLC fingerprint, and interspecific hybridization studies
of genus epimedium (berberidaceae).
AB - 104 samples from 27 accessions belonging to 12 species of genus Epimedium were
studied on the basis of cytology observation, POD (i.e., peroxide) isozyme, high
performance liquid chromatography (i.e., HPLC) fingerprint, and interspecific
hybridization. The cytology observation showed karyotypes of twelve species
studied; all are 2A symmetry type of Stebbins standard and similar to each other,
and except for karyotype of E. leptorrhizum which is 2n = 2x = 8m (2SAT) + 4sm,
the rest are 2n = 2x = 6m (2SAT) + 6sm. Chromosomes C-banding of barrenwort
species varies, with 15 to 22 bands, consisting of centromeric bands, intercalary
bands, terminal bands, and middle satellite bands. Results of POD isozyme showed
that the zymographs vary greatly and sixteen bands were detected in the eleven
species, and each species has its own characteristic bands different from the
others. Studies on the HPLC fingerprint showed that the HPLC fingerprint of
different species has characteristic peaks, divided into two regions (retention
time < 10 min and retention time > 10 min). Results of interspecific
hybridization showed that crosses of any combination among seven species studied
are successful and the rates of grain set vary greatly. Based on these results,
the system and phylogeny of this genus were inferred.
PMID- 24349796
TI - The Relationship between Personality Type and Acceptable Noise Levels: A Pilot
Study.
AB - Objectives. This study examined the relationship between acceptable noise level
(ANL) and personality. ANL is the difference between a person's most comfortable
level for speech and the loudest level of background noise they are willing to
accept while listening to speech. Design. Forty young adults with normal hearing
participated. ANLs were measured and two personality tests (Big Five Inventory,
Myers-Briggs Type Indicator) were administered. Results. The analysis revealed a
correlation between ANL and the openness and conscientious personality dimensions
from the Big Five Inventory; no correlation emerged between ANL and the Myers
Briggs personality types. Conclusions. Lower ANLs are correlated with full-time
hearing aid use and the openness personality dimension; higher ANLs are
correlated with part-time or hearing aid nonuse and the conscientious personality
dimension. Current data suggest that those more open to new experiences may
accept more noise and possibly be good hearing aid candidates, while those more
conscientious may accept less noise and reject hearing aids, based on their
unwillingness to accept background noise. Knowing something about a person's
personality type may help audiologists determine if their patients will likely be
good candidates for hearing aids.
PMID- 24349797
TI - A simple spatial working memory and attention test on paired symbols shows
developmental deficits in schizophrenia patients.
AB - People with neuropsychiatric disorders such as schizophrenia often display
deficits in spatial working memory and attention. Evaluating working memory and
attention in schizophrenia patients is usually based on traditional tasks and the
interviewer's judgment. We developed a simple Spatial Working Memory and
Attention Test on Paired Symbols (SWAPS). It takes only several minutes to
complete, comprising 101 trials for each subject. In this study, we tested 72
schizophrenia patients and 188 healthy volunteers in China. In a healthy control
group with ages ranging from 12 to 60, the efficiency score (accuracy divided by
reaction time) reached a peak in the 20-27 age range and then declined with
increasing age. Importantly, schizophrenia patients failed to display this
developmental trend in the same age range and adults had significant deficits
compared to the control group. Our data suggests that this simple Spatial Working
Memory and Attention Test on Paired Symbols can be a useful tool for studies of
spatial working memory and attention in neuropsychiatric disorders.
PMID- 24349799
TI - Improved method for the quantification of motility in glia and other
morphologically complex cells.
AB - Cells such as astrocytes and radial glia with many densely ramified, fine
processes pose particular challenges for the quantification of structural
motility. Here we report the development of a method to calculate a motility
index for individual cells with complex, dynamic morphologies. This motility
index relies on boxcar averaging of the difference images generated by
subtraction of images collected at consecutive time points. An image
preprocessing step involving 2D projection, edge detection, and dilation of the
raw images is first applied in order to binarize the images. The boxcar averaging
of difference images diminishes the impact of artifactual pixel fluctuations
while accentuating the group-wise changes in pixel values which are more likely
to represent real biological movement. Importantly, this provides a value that
correlates with mean process elongation and retraction rates without requiring
detailed reconstructions of very complex cells. We also demonstrate that
additional increases in the sensitivity of the method can be obtained by
denoising images using the temporal frequency power spectra, based on the fact
that rapid intensity fluctuations over time are mainly due to imaging artifact.
The MATLAB programs implementing these motility analysis methods, complete with
user-friendly graphical interfaces, have been made publicly available for
download.
PMID- 24349798
TI - NMDA reduces Tau phosphorylation in rat hippocampal slices by targeting NR2A
receptors, GSK3beta, and PKC activities.
AB - The molecular mechanisms that regulate Tau phosphorylation are complex and
currently incompletely understood. In the present study, pharmacological
inhibitors were deployed to investigate potential processes by which the N-methyl
D-aspartate (NMDA) subtype of glutamate receptors modulates Tau phosphorylation
in rat hippocampal slices. Our results demonstrated that Tau phosphorylation at
Ser199-202 residues was decreased in NMDA-treated hippocampal slices, an effect
that was not reproduced at Ser262 and Ser404 epitopes. NMDA-induced reduction of
Tau phosphorylation at Ser199-202 was further promoted when NR2A-containing
receptors were pharmacologically isolated and were completely abrogated by the
NR2A receptor antagonist NVP-AAM077. Compared with nontreated slices, we observed
that NMDA receptor activation was reflected in high Ser9 and low Tyr216
phosphorylation of glycogen synthase kinase-3 beta (GSK3beta), suggesting that
NMDA receptor activation might diminish Tau phosphorylation via a pathway
involving GSK3beta inhibition. Accordingly, we found that GSK3beta inactivation
by a protein kinase C- (PKC-) dependent mechanism is involved in the NMDA-induced
reduction of Tau phosphorylation at Ser199-202 epitopes. Taken together, these
data indicate that NR2A receptor activation may be important in limiting Tau
phosphorylation by a PKC/GSK3beta pathway and strengthen the idea that these
receptors might act as an important molecular device counteracting neuronal cell
death mechanisms in various pathological conditions.
PMID- 24349795
TI - VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review.
AB - Vesicular glutamate transporters (VGLUTs) are key molecules for the incorporation
of glutamate in synaptic vesicles across the nervous system, and since their
discovery in the early 1990s, research on these transporters has been intense and
productive. This review will focus on several aspects of VGLUTs research on
neurons in the periphery and the spinal cord. Firstly, it will begin with a
historical account on the evolution of the morphological analysis of
glutamatergic systems and the pivotal role played by the discovery of VGLUTs.
Secondly, and in order to provide an appropriate framework, there will be a
synthetic description of the neuroanatomy and neurochemistry of peripheral
neurons and the spinal cord. This will be followed by a succinct description of
the current knowledge on the expression of VGLUTs in peripheral sensory and
autonomic neurons and neurons in the spinal cord. Finally, this review will
address the modulation of VGLUTs expression after nerve and tissue insult, their
physiological relevance in relation to sensation, pain, and neuroprotection, and
their potential pharmacological usefulness.
PMID- 24349800
TI - Increased signal complexity improves the breadth of generalization in auditory
perceptual learning.
AB - Perceptual learning can be specific to a trained stimulus or optimally
generalized to novel stimuli with the breadth of generalization being imperative
for how we structure perceptual training programs. Adapting an established
auditory interval discrimination paradigm to utilise complex signals, we trained
human adults on a standard interval for either 2, 4, or 10 days. We then tested
the standard, alternate frequency, interval, and stereo input conditions to
evaluate the rapidity of specific learning and breadth of generalization over the
time course. In comparison with previous research using simple stimuli, the speed
of perceptual learning and breadth of generalization were more rapid and greater
in magnitude, including novel generalization to an alternate temporal interval
within stimulus type. We also investigated the long term maintenance of learning
and found that specific and generalized learning was maintained over 3 and 6
months. We discuss these findings regarding stimulus complexity in perceptual
learning and how they can inform the development of effective training protocols.
PMID- 24349801
TI - Clinical and imaging findings of true hemifacial hyperplasia.
AB - Congenital hemifacial hyperplasia is a rare developmental disorder of unknown
etiology, characterized by a marked unilateral facial asymmetry. It involves the
hard (bones and teeth) and soft tissues of the face. We report an interesting
case of true hemifacial hyperplasia in a 25-year-old male highlighting the
clinical and computed tomography imaging findings.
PMID- 24349802
TI - Rapidly progressing osteomyelitis of the mandible.
AB - Acute osteomyelitis exists as a refractory disease even now, which usually
exhibits systemic symptoms such as fever or malaise and local redness or
swelling. The present paper describes a case of acute osteomyelitis of the
mandible that was rapidly progressing without typical symptoms. The patient had
liver cirrhosis, which should be one of the systemic factors that affect immune
surveillance and metabolism. Actinomycotic druses and filaments were detected
from the sequestrum. These were considered to play a role in the rapid
progression of osteomyelitis without typical symptoms. There has been no evidence
of local recurrence 24 months after surgery.
PMID- 24349803
TI - Management of Extramammary Paget's Disease: A Case Report and Review of the
Literature.
AB - Extramammary Paget's Disease (EMPD) is a rare condition of the skin that often
involves the vulva, perianal region, scrotum, penis, and axilla. Although
prognosis is generally favorable, it can be associated with neoplasms of the
bladder, urethra, prostate, and rectum. This report presents a case of scrotal
EMPD that failed treatment with imiquimod 5% cream and discusses benefits and
complications of available treatment options. The variation of treatment success
emphasizes the importance of further research.
PMID- 24349804
TI - Paediatric orbital fractures: the importance of regular thorough eye assessment
and appropriate referral.
AB - The paediatric orbital fracture should always raise alarm bells to all clinicians
working in an emergency department. A delay or failure in diagnosis and
appropriate referral can result in rapidly developing and profound complications.
We present a boy of childhood age who sustained trauma to his eye during a
bicycle injury. Acceptance of the referral was based on no eye signs; however, on
examination in our unit the eye had reduction in visual acuity, no pupillary
reaction, and ophthalmoplegia. CT scan suggested bone impinging on the globe and
the child was rushed to theatre for removal of the bony fragment. Postoperatively
no improvement was noted and a diagnosis of traumatic optic neuropathy was made.
An overview of factors complicating paediatric orbital injuries, their associated
"red flags", and appropriate referral are discussed in this short paper.
PMID- 24349805
TI - Biclonal IgD and IgM Plasma Cell Myeloma: A Report of Two Cases and a Literature
Review.
AB - Biclonal plasma cell myelomas producing two different isotypes of immunoglobulins
are extremely rare entities; to date, the combination of IgD and IgM secretion by
a biclonal plasma cell myeloma has not been reported. Bone marrow biopsy
immunohistochemical studies in two cases revealed neoplastic plasma cells
coexpressing IgD and IgM, but serum protein electrophoresis identified only the
IgM monoclonal paraprotein in both cases. Biclonal plasma cell myelomas, while
currently not well characterized in terms of their clinical behavior, should be
distinguished from B-cell lymphoma with plasmacytic differentiation, given the
different therapeutic implications. Both cases reported herein demonstrated
chemotherapy-resistant clinical courses.
PMID- 24349806
TI - The Sinus That Breeds Fungus: Subcutaneous Zygomycosis Caused by Basidiobolus
ranarum at the Injection Site.
AB - Subcutaneous zygomycosis is caused by Basidiobolus ranarum which is endemic in
India. We report a case of a housewife who presented with a persistent
discharging sinus from the right gluteal region subsequent to an intramuscular
injection which was refractory to empirical antituberculous therapy. She
underwent an excision of the sinus tract, the culture of which yielded B.
ranarum. The wound improved with oral potassium iodide.
PMID- 24349807
TI - A case of placental mesenchymal dysplasia.
AB - Placental mesenchymal dysplasia (PMD) rarely complicates with pregnancy. A 30
year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred
to our department at 18 weeks of gestation. An ultrasonography revealed a normal
fetus with a large multicystic placenta, measuring 125 * 42 * 80 mm. The border
between the lesion and normal region was not clear. Color doppler revealed little
blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a
large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97
U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal
dysplasia rather than hydatidiform mole with coexistent fetus was suspected.
Then, routine checkup was continued. Because she had the history of Cesarean
section, an elective Cesarean section was performed at 37 weeks of gestation, and
2520 g female infant with apgar score 8/9 was delivered. The baby was normal with
no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 * 16 * 2 cm, weighing
720 g, was bulky with grape like vesicles involving whole placenta. Microscopic
examination revealed dilated villi and vessels with thick wall which was lacking
trophoblast proliferation. Large hydropic stem villi with myxomatous struma and
cistern formation were seen. PMD was histopathologically confirmed.
PMID- 24349808
TI - Spontaneous twin pregnancy in uterus bicornis unicollis.
AB - Abnormal fusion of the Mullerian ducts or failure of resorption of the septum
causes varying degrees of congenital uterine malformation. They are often
associated with reproductive problems such as miscarriage, premature labour,
premature rupture of the membranes, or malpresentation. Twin gestation in a case
of bicornuate uterus is extremely rare. A 37-year-old multiparous woman conceived
a twin dichorionic diamniotic pregnancy spontaneously. Three-dimensional
ultrasound revealed bicornuate uterus with one embryo in each cavity. Perinatal
course was uneventful. At 35 weeks of pregnancy, spontaneous labour started and
twin babies were delivered by bilateral low transvers caesarean section. Because
of the rare occurrence of twin gestation in bicornuate uterus, there is no
uniform guideline to manage these cases appropriately. Delivery by planned
caesarean section could avoid the possible obstetric complications by dystocia.
PMID- 24349809
TI - Diagnosing a gastric submucosal tumor using jumbo biopsy "unroofing" technique: a
case report and review of the literature.
AB - We report a case of a 40-year-old female who presented with dyspeptic symptoms
for six months. Upper GI endoscopy revealed a submucosal nodule in gastric
antrum. Using "jumbo biopsy unroofing technique" we were able to get adequate
tissue for analysis. Histopathology revealed a type III gastric carcinoid.
Patient was treated with laparoscopic distal subtotal gastrectomy with Roux-en-Y
reconstruction and partial omentectomy. Although there was no evidence of
metastasis on initial presentation, eighteen months later, patient was found to
have multiple metastatic lesions in her liver. Patient's lesions were treated
with intra-arterial (hepatic artery) Yttrium-90.
PMID- 24349810
TI - Atypical B12 deficiency with nonresolving paraesthesia.
AB - Vitamin B12 deficiency can present with various hematological, gastrointestinal
and neurological manifestations. We report a case of elderly female who presented
with neuropathy and vitamin B12 deficiency where the final work-up revealed
polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes (POEMS). This case suggests that, although POEMS syndrome is a rare
entity, it can present with vitamin-B12 deficiency and thus specific work up for
early diagnosis of POEMS should be considered in patients with B12 deficiency
unresponsive to therapy.
PMID- 24349811
TI - Nonalpine thyroid angiosarcoma in a patient with hashimoto thyroiditis.
AB - Thyroid angiosarcoma is an uncommon thyroid carcinoma and its incidence is the
highest in the European Alpine regions. Thyroid angiosarcoma is also a very
aggressive tumor that can rapidly spread to the cervical lymph nodes, lungs, and
brain or can metastasize to the duodenum, small boewl, and large bowel. Although
it is histologically well defined, clear-cut separation between the angiosarcoma
and anaplastic thyroid carcinoma is difficult. A 49-year-old Caucasian female
patient, born and resident in Southern Italy (Calabria), in an iodine-sufficient
area, was admitted to the Surgery Department because she presented with a
painless mass in the anterior region of neck enlarged rapidly in the last three
months. After total thyroidectomy and right cervical lymphadenectomy,
postoperative histological examination revealed the presence of a thyroid
angiosarcoma with positive staining for CD31 and for both Factor VIII-related
antigen and Vimentin and only partially positive for staining pancytokeratin and
presence of metastasis in cervical, supraclavicular, mediastinal and paratracheal
lymph nodes. The patient started adjuvant chemotherapy and she was treated for 6
cycles with Doxorubicin, Dacarbazine, Ifosfamide, and Mesna (MAID). After 22
months from surgery, the patient is still alive without both local and systemic
recurrence of the disease.
PMID- 24349812
TI - Removal of a broken cannulated femoral nail: a novel retrograde impaction
technique.
AB - This report presents a surgical technique to remove a broken cannulated nail from
the femur. A Harrington rod was modified for retrograde impaction of the retained
fragment. The broken implant was finally removed without complication. This
particular procedure was safe, simple, and promising.
PMID- 24349813
TI - Amantadine-induced patulous eustachian tubes in Parkinson's disease.
AB - Patulous Eustachian tube (PET) is a common condition that produces symptoms of
aural fullness and autophony. We describe a Parkinson's disease (PD) patient that
experienced a reversible bilateral patulous (hyperpatent) Eustachian tube
syndrome induced by treatment with amantadine hydrochloride. The clinical
features, relevant anatomy and physiology, and associated risk factors for PET
are reviewed.
PMID- 24349814
TI - A rare case of congenital rhabdomyosarcoma with review of the literature.
AB - We present a rare case of rhabdomyosarcoma of lip in a neonate with multiple
lesions within the head and necksub site hitherto unreported in the medical
literature. This case report also reviews the scant medical literature on
neonatal rhabdomyosarcoma.
PMID- 24349815
TI - Dermoid cyst of the pancreas: a report of an unusual case and a review of the
literature.
AB - Pancreatic dermoid cysts are a rare entity. Preoperative diagnosis is difficult.
The diagnosis is generally taking intraoperative. A 20-year-old female presented
with epigastric pain without nausea, vomiting, diarrhea, fever, jaundice, and
weight loss of one-month duration. Ultrasonography and computed tomography showed
a smooth borders, solid, hyperechoic tumor within midline abdomen, without any
connection to the stomach or spleen. At surgery, the entire mass was excised off
of the head and inferior part of pancreas. Histopathologic evaluation revealed
the rare diagnosis of a dermoid cyst. The diagnosis is difficult preoperatively
in evaluating cystic pancreatic lesions by imaging. Therefore, we want to
summarize the literature on this rare entity knowledge.
PMID- 24349816
TI - Rare case of a chondrosarcoma of the mandible in a child.
AB - Chondrosarcoma of the mandible is rare, especially in children. The available
literature consists mostly of a few case reports which are partly integrated in
small studies. Growing this small pool of literature is helpful in solidifying
knowledge about this disease and facilitating appropriate treatment for children.
Therefore, we present such a case in a 12-year-old boy, exhibit comprehensive and
relevant information concerning this entity, and discuss our findings in the
context of other publications.
PMID- 24349817
TI - Nutcracker syndrome complicated by left renal vein thrombosis.
AB - Isolated renal vein thrombosis is a rare entity. We present a patient whose
complaint of flank pain led to the diagnosis of a renal vein thrombosis. In this
case, abdominal computed tomography angiography was helpful in diagnosing the
nutcracker syndrome complicated by the renal vein thrombosis. Anticoagulation was
started and three weeks later, CTA showed complete disappearance of the renal
vein thrombosis. To treat the Nutcracker syndrome, we proposed left renal vein
transposition that the patient consented to.
PMID- 24349818
TI - IgG4-Related Autoimmune Prostatitis: Is It an Unusual or Underdiagnosed
Manifestation of IgG4-Related Disease?
AB - IgG4-related disease (IgG4-RD) encompasses a wide range of extrapancreatic
manifestations. Albeit some are relatively well known, others such as autoimmune
prostatitis remain poorly described. We present a 61-year-old Latin-American male
with autoimmune pancreatitis (AIP) who presented with lower urinary tract
symptoms (LUTS), normal prostate specific antigen (PSA) test, and prostate
enlargement attributed to benign prostatic hyperplasia (BPH). He underwent a
transurethral resection of the prostate (TURP) after which symptoms were
resolved. On histopathology, prostatic stroma had a dense inflammatory infiltrate
rich in plasma cells and lymphocytes; immunohistochemical morphometric assessment
showed >10 IgG4-positive plasma cells/high power field (HPF). The diagnosis of
IgG4-related prostatitis was postoperatively. We compared the patient
characteristics with those of previous reports on Asian patients. Shared findings
included prostate enlargement, LUTS (symptoms that can be confused with BPH), and
PSA within normal limits or mild elevations. IgG4-related prostatitis is rarely
considered as a preprocedural diagnosis, even in patients with evidence of IgG4
RD. Involved prostate zones include mainly central and transitional zones and
less frequently the peripheral. Currently, there is insufficient data about the
natural history and outcome. Whether steroids, transurethral resection, or both
are the treatment of choice needs to be elucidated.
PMID- 24349819
TI - Retroperitoneal lipoma presenting with nutcracker-like phenomenon.
AB - Retroperitoneal lipoma presenting with a nutcracker-like phenomenon is extremely
rare. I experienced a case of a 65-year-old man presenting with left flank pain
and macrohematuria intermittently for 3 years. Computed tomography revealed a
lipoma at the left pedicle of the kidney, 30 mm in diameter, causing a curving of
the left renal artery and dilatation of the left renal vein. This patient was
treated successfully by retroperitoneoscopic resection of the lipoma. There have
been no symptoms for 10 years after the operation.
PMID- 24349820
TI - Acoustic Emission Signal of Lactococcus lactis before and after Inhibition with
NaN 3 and Infection with Bacteriophage c2.
AB - The detection of acoustic emission (AE) from Lactococcus lactis, ssp lactis is
reported in which emission intensities are used to follow and define metabolic
activity during growth in nutrient broths. Optical density (OD) data were also
acquired during L. lactis growth at 32 degrees C and provided insight into the
timing of the AE signals relative to the lag, logarithmic, and stationary growth
phases of the bacteria. The inclusion of a metabolic inhibitor, NaN3, into the
nutrient broth eliminated bacteria metabolic activity according to the OD data,
the absence of which was confirmed using AE data acquisition. The OD and AE data
were also acquired before and after the addition of Bacteriophage c2 in L. lactis
containing nutrient broths during the early or middle logarithmic phase; c2 phage
m.o.i. (Multiplicity of infection) was varied to help differentiate whether the
detected AE was from bacteria cells during lysis or from the c2 phage during
genome injection into the cells. It is proposed that AE measurements using
piezoelectric sensors are sensitive enough to detect bacteria at the amount near
10(4) cfu/mL, to provide real time data on bacteria metabolic activity and to
dynamically monitor phage infection of cells.
PMID- 24349821
TI - Vitamin d predicts all-cause and cardiac mortality in females with suspected
acute coronary syndrome: a comparison with brain natriuretic Peptide and high
sensitivity C-reactive protein.
AB - Vitamin D may not only reflect disease but may also serve as a prognostic
indicator. Our aim was to assess the gender-specific utility of vitamin D
measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death
in patients with suspected acute coronary syndrome (ACS) and to compare its
prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C
reactive protein (hsCRP). Blood samples were harvested on admission in 982
patients. Forty percent were women (65.9 +/- 12.6 years). Mortality was evaluated
in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up,
applying univariate and multivariate analyses. One hundred and seventy-three
patients died; 78 were women. In 92 patients (37 women), death was defined as
cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in
Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33
0.93), 0.29 (95% CI 0.15-0.55), and 0.13 (95% CI 0.06-0.32), respectively. In
females, it was an independent predictor of total and cardiac death, whereas BNP
and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted
in a reference material. Accordingly, vitamin D independently predicts mortality
in females with suspected ACS.
PMID- 24349823
TI - Effects of pH, Temperature, Dissolved Oxygen, and Flow Rate on Phosphorus Release
Processes at the Sediment and Water Interface in Storm Sewer.
AB - The effects of pH, temperature, dissolved oxygen (DO), and flow rate on the
phosphorus (P) release processes at the sediment and water interface in rainwater
pipes were investigated. The sampling was conducted in a residential storm sewer
of North Li Shi Road in Xi Cheng District of Beijing on August 3, 2011. The
release rate of P increased with the increase of pH from 8 to 10. High
temperature is favorable for the release of P. The concentration of total
phosphorus (TP) in the overlying water increased as the concentration of DO
decreased. With the increase of flow rate from 0.7 m s(-1) to 1.1 m s(-1), the
concentration of TP in the overlying water increased and then tends to be stable.
Among all the factors examined in the present study, the flow rate is the primary
influence factor on P release. The cumulative amount of P release increased with
the process of pipeline runoff in the rainfall events with high intensities and
shorter durations. Feasible measures such as best management practices and low
impact development can be conducted to control the P release on urban sediments
by slowing down the flow rate.
PMID- 24349822
TI - Does a history of migraine affect the rate of thrombolysis in young stroke
patients?
AB - Background. Migraine is prevalent in young patients and a frequent stroke mimic.
To distinguish stroke mimics from true stroke can be difficult, and there is a
possibility of misdiagnosing a stroke as a migrainous attack in patients with
migraine. We aimed to investigate if a history of migraine affects the rate of
thrombolytic therapy in young stroke patients. Methods. All patients below 50
years of age admitted in the period 2006-2013 to the Bergen Stroke Centre with
acute ischaemic stroke were included. The rate of thrombolytic therapy in
patients with migraine was compared to patients with no history of migraine. A
multivariate analysis was performed to adjust confounding factors. Results. A
total of 170 young stroke patients were enrolled, 49 with migraine and 121 with
no migraine. In total, 10.2% of young patients with migraine received
thrombolytic therapy, compared with 26.5% of young patients with nomigraine (P =
0.02). Migraine was associated with a low rate of thrombolytic therapy when
adjusting for possible confounding factors (OR 0.19 CI: 0.05-0.72, P = 0.02).
Conclusion. Migraine is associated with a low rate of thrombolytic therapy in
young patients admitted with acute ischaemic stroke. Migraine patients admitted
with acute ischaemic stroke are at risk of maltreatment.
PMID- 24349824
TI - Optimization of IC Separation Based on Isocratic-to-Gradient Retention Modeling
in Combination with Sequential Searching or Evolutionary Algorithm.
AB - GRADIENT ION CHROMATOGRAPHY WAS USED FOR THE SEPARATION OF EIGHT SUGARS:
arabitol, cellobiose, fructose, fucose, lactulose, melibiose, N-acetyl-D
glucosamine, and raffinose. The separation method was optimized using a
combination of simplex or genetic algorithm with the isocratic-to-gradient
retention modeling. Both the simplex and genetic algorithms provided well
separated chromatograms in a similar analysis time. However, the simplex
methodology showed severe drawbacks when dealing with local minima. Thus the
genetic algorithm methodology proved as a method of choice for gradient
optimization in this case. All the calculated/predicted chromatograms were
compared with the real sample data, showing more than a satisfactory agreement.
PMID- 24349825
TI - The GC/MS Analysis of Volatile Components Extracted by Different Methods from
Exocarpium Citri Grandis.
AB - Volatile components from Exocarpium Citri Grandis (ECG) were, respectively,
extracted by three methods, that is, steam distillation (SD), headspace solid
phase microextraction (HS-SPME), and solvent extraction (SE). A total of 81
compounds were identified by gas chromatography-mass spectrometry including 77
(SD), 56 (HS-SPME), and 48 (SE) compounds, respectively. Despite of the
extraction method, terpenes (39.98~57.81%) were the main volatile components of
ECG, mainly germacrene-D, limonene, 2,6,8,10,14-hexadecapentaene, 2,6,11,15
tetramethyl-, (E,E,E)-, and trans-caryophyllene. Comparison was made among the
three methods in terms of extraction profile and property. SD relatively gave an
entire profile of volatile in ECG by long-time extraction; SE enabled the
analysis of low volatility and high molecular weight compounds but lost some
volatiles components; HS-SPME generated satisfactory extraction efficiency and
gave similar results to those of SD at analytical level when consuming less
sample amount, shorter extraction time, and simpler procedure. Although SD and SE
were treated as traditionally preparative extractive techniques for volatiles in
both small batches and large scale, HS-SPME coupled with GC/MS could be useful
and appropriative for the rapid extraction and qualitative analysis of volatile
components from medicinal plants at analytical level.
PMID- 24349826
TI - Simultaneous Determination of Volatile Constituents from Acorus tatarinowii
Schott in Rat Plasma by Gas Chromatography-Mass Spectrometry with Selective Ion
Monitoring and Application in Pharmacokinetic Study.
AB - A sensitive and specific gas chromatographic-mass spectrometry with selected ion
monitoring (GC-MS/SIM) method has been developed for simultaneous identification
and quantification of alpha -asarone, beta-asarone, and methyl eugenol of Acorus
tatarinowii Schott in rat plasma. Chromatographic separation was performed on a
Restek Rxi-5MS capillary column (30 m * 0.32 mm * 0.25 MUm), using 1-naphthol as
internal standard (IS). MS detection of these compounds and IS was performed at
m/z 178, 208, 208, and 144. Intra- and interday precisions of all compounds of
interest were less than 10%. The recoveries are situated in the range of 92.4
105.2%. Pharmacokinetics of methyl eugenol confirmed to be one-compartment open
model, alpha -asarone and beta -asarone was two-compartment open model,
respectively. The method will probably be an alternative to simultaneous
determination and pharmacokinetic study of volatile ingredients in Acorus
tatarinowii Schott.
PMID- 24349827
TI - Global progress against cancer-challenges and opportunities.
AB - The last ten years have seen remarkable progress in cancer research. However,
despite significant breakthroughs in the understanding, prevention, and treatment
of cancer, the disease continues to affect millions of people worldwide. Cancer's
complexity compounded with financial, policy and regulatory roadblocks has slowed
the rate of progress being made against cancer. In this paper, we review a few of
the most recent breakthroughs that are fueling medical advances and bringing new
hope for patients affected by this devastating disease. We also address the
challenges facing us and the opportunities to accelerate future progress against
cancer. The efforts of the American Association for Cancer Research (AACR) to
address the cancer burden already extend beyond the borders of the United States
of America. The AACR is committed to increasing its efforts to stem the tide of
cancer worldwide by promoting innovative programs, strategies, and initiatives
for cancer researchers and all those engaged in cancer-related biomedical
sciences around the world.
PMID- 24349828
TI - Asian trends in primary androgen depletion therapy on prostate cancer.
AB - There are notable differences in the incidence and mortality rates for prostate
cancer between Asia and Western countries. It is also recognized that there are
differences in thinking with regard to treatment options. Recently it is also the
case that opinions have been reported concerning the differences between Asian
and Western patients with regard to their reaction to androgen depletion therapy
(ADT). Given that ADT is a method of treatment that focuses on the elimination of
testosterone, an inevitable symptom of its administration is testosterone losing
syndrome. It is for this reason that in Western countries ADT has only been
recommended in cases of advanced or metastatic cancer. On the other hand, in
Asia, ADT is used in relatively many cases, including non-metastatic localized
cancer and invasive localized cancer. To date, however, there has been little
substantive discussion concerning this difference in utilization of ADT. ADT
related drugs for prostate cancer and the development of new drugs for castration
resistant prostate cancer (CRPC) have been actively tested in recent years. It
could be the case that analyzing the differences in concepts about ADT between
Asia and the West could contribute to the effective use of ADT-related drugs and
also help to build new treatment strategies for prostate cancer.
PMID- 24349830
TI - Why bortezomib cannot go with 'green'?
AB - Eat more 'green' or eat 'five a day' is one of the most important healthy
lifestyle behaviours in the 21 century. Aiming to fight cancer effectively, more
than half patients use vitamins or herbs concurrently with conventional
anticancer treatment. Flavonoids or polyphenols existing in vegetables, fruits
and green tea are common plant pigments with antioxidant properties and
considered acting as cancer preventing or anti-cancer agents. Recently it was
found that some flavonoids and vitamin C in diet or supplements have antagonistic
effect with the anti-cancer drug bortezomib. Bortezomib is a specific inhibitor
for proteasome and is currently used for treatment of relapsed and refractory
multiple myeloma. Despite its successful rates in treating multiple myeloma and
other solid tumors, it is unable to kill leukemic cells in the blood. It was
recently revealed that some flavonoids and vitamin C present in green leaves and
green teas in the blood can neutralize bortezomib by directly interaction between
two chemicals. Here we summarize why dietary flavonoids should be avoided in
patients who take bortezomib as chemotherapeutic drug.
PMID- 24349829
TI - Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks.
AB - Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor
(EGFR) regulate cellular homeostatic processes. EGFR activates downstream
signaling cascades that promote tumor cell survival, proliferation and migration.
Dysregulation of EGFR signaling as a consequence of overexpression, amplification
and mutation of the EGFR gene occurs frequently in several types of cancers and
many become dependent on EGFR signaling to maintain their malignant phenotypes.
Consequently, concerted efforts have been mounted to develop therapeutic agents
and strategies to effectively inhibit EGFR. However, limited therapeutic benefits
to cancer patients have been derived from EGFR-targeted therapies. A well
documented obstacle to improved patient survival is the presence of EGFR
inhibitor resistant tumor cell variants within heterogeneous tumor cell masses.
Here, we summarize the mechanisms by which tumors resist EGFR-targeted therapies
and highlight the emerging role of microRNAs (miRs) as downstream effector
molecules utilized by EGFR to promote tumor initiation, progression and that play
a role in resistance to EGFR inhibitors. We also examine evidence supporting the
utility of miRs as predictors of response to targeted therapies and novel
therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.
PMID- 24349832
TI - Effects of HLEC on the secreted proteins of epithelial ovarian cancer cells prone
to metastasize to lymph nodes.
AB - OBJECTIVE: To study explores the effect of HLEC on the secreted proteins of
epithelial ovarian cancer (EOC) cells (SKOV3-PM4) with directional highly
lymphatic metastasis. METHODS: Supernatants of four groups of cultured cells,
namely, SKOV3 (A), SKOV3+HLEC (B), SKOV3-PM4 (C), SKOV3-PM4+HLEC (D), were
collected, and their proteins were detected by antibody arrays and iTRAQ-2D-LC
MALDI-TOF/TOF/MS. Significantly differential proteins were further analyzed via
bioinformatics and validated in human serums and cell media via ELISA. RESULTS:
Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA
were upregulated in group C (compared with group A), whereas IGFBP7 and SPARC
were downregulated in group D (compared with group C). Comprehensive
bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked
to each other. Further validation with serums showed statistical significance in
VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign
tumors, and control groups. Two proteins were upegulated in the first group.
VEGFA in the control group was downregulated. For IGFBP, upregulation in the
control group and down-regulation in the first group were also observed.
CONCLUSION: The HLEC microenvironment is closely associated with directional
metastasis to lymph nodes and with differential proteins including cell stromal
proteins and adhesion factors. The upregulation of VEGFA and GRN and the
downregulation of SPARC and IGFBP7 are closely associated with directional
metastasis to lymph nodes in EOC cells.
PMID- 24349831
TI - Translational genomics in cancer research: converting profiles into personalized
cancer medicine.
AB - Cancer genomics is a rapidly growing discipline in which the genetic molecular
basis of malignancy is studied at the scale of whole genomes. While the
discipline has been successful with respect to identifying specific oncogenes and
tumor suppressors involved in oncogenesis, it is also challenging our approach to
managing patients suffering from this deadly disease. Specifically cancer
genomics is driving clinical oncology to take a more molecular approach to
diagnosis, prognostication, and treatment selection. We review here recent work
undertaken in cancer genomics with an emphasis on translation of genomic
findings. Finally, we discuss scientific challenges and research opportunities
emerging from findings derived through analysis of tumors with high-depth
sequencing.
PMID- 24349833
TI - Analysis of 30 patients with persistent or recurrent squamous cell carcinoma of
the cervix within one year after concurrent chemoradiotherapy.
AB - OBJECTIVE: To investigate the recurrence sites, risk factors, and prognosis of
patients with persistent or recurrent squamous cell carcinoma (SCC) of the cervix
within one year after undergoing concurrent chemoradiotherapy (CCRT). METHODS:
Clinical data of 30 patients with persistent or recurrent SCC of the cervix
within one year after CCRT between July 2006 and July 2011 were analyzed
retrospectively. These data were compared with those of 35 SCC cases with no
signs of recurrence after complete remission. These 35 patients were treated
during the same period (between 2006 and 2011) and selected randomly. RESULTS:
Among these 30 patients, 25 exhibited distant metastases of which 14 were
observed within 6 months after CCRT. Univariate analysis showed higher incidence
of pelvic or para-aortic lymphadenectasis and SCC-ag >10 ng/mL in the group with
persistent or recurrent disease before treatment (P<0.01). Multivariate analysis
by logistic regression revealed that the pre-therapeutic pelvic or para-aortic
lymph node enlargement and SCC-ag >10 ng/mL were the independent risk factors.
Palliative chemotherapy was the main treatment option for patients with
persistent or recurrent disease. The 2-year survival rate was 21.7%, and the
median survival time was 17 months. CONCLUSION: Patients with persistent or
recurrent SCC of the cervix after CCRT exhibited a high rate of distant
metastasis with poor prognosis. The pre-therapeutic pelvic or para-aortic lymph
node enlargement and SCC-ag >10 ng/mL were identified as the independent risk
factors for persistent or recurrent SCC within 1 year after CCRT.
PMID- 24349834
TI - Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic
mobilization peripheral blood stem cell transplantation.
AB - Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de
novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be
an initial manifestation of relapse in a previously treated AML that is in
remission. A 44-year-old male patient was diagnosed with testis MS in a local
hospital in August 2010. After one month, bone marrow biopsy and aspiration
confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem
cell transplantation was performed, with the sister of the patient as donor,
after complete remission (CR) was achieved by chemotherapy. Five months after
treatment, an adrenal mass was detected by positron emission tomography-computed
tomography (PET-CT). Radiotherapy was performed for the localized mass after a
multidisciplinary team (MDT) discussion. The patient is still alive as of May
2013, with no evidence of recurrent MS or leukemia.
PMID- 24349835
TI - Unusual unilateral multiple muscular variations of back of thigh.
AB - During routine cadaveric dissection for the undergraduate students in the
Department of Anatomy, we noted multiple muscular variations in a middle-aged
male cadaver. All the variations were seen at the back of thigh (flexor
compartment) of right lower limb. An anomalous muscle of 17 cm length with
average width of 1.5 cm. was inserted to the semitendinosus, a third head of
biceps femoris of 6.5 cm length with an average width of 3.5 cm was inserted to
the semitendinosus and ununited short and long heads of biceps femoris, both
heads were inserted to the head of fibula. To the best of our knowledge, such
muscular variations have not been reported in the recent medical literature. A
comprehensive knowledge of such rare anatomical variations will be important for
surgeons and Traumatologists as this might cause compression of the sciatic
nerve.
PMID- 24349836
TI - Endometrial osseous metaplasia: case report with literature review.
AB - Endometrial osseous metaplasia is a rare pathological condition with mature bone
in the endometrium and can be a cause for menorrhagia and infertility as bone in
the endometrium acts like intrauterine contraceptive device. We report one such
case with brief review of literature in a 28-year-old woman presenting with
history of menorrhagia.
PMID- 24349837
TI - Twin fetuses papyraeci in a spontaneous triplet pregnancy presenting with
unexplained preterm contractions.
AB - Fetus papyracie in a triplet pregnancy is indeed rare and can pose serious
management challenges. These challenges are more pronounced where facilities for
monitoring are either inadequate or nonexistent. A 39-year-old, grand multipara
multipara was referred to the University of Maiduguri Teaching Hospital at 27
weeks gestation with preterm contractions. Materno fetal monitoring did not
reveal the cause of the preterm contractions. She was delivered via caesarean
section, at 36 weeks of gestation, on account of decreased fetal movement and the
products were a live female fetus weighing 2.3 kg and two male papyraceous
fetuses weighing 150 g and 130 g, respectively.
PMID- 24349838
TI - A case report of Plasmodium vivax, Plasmodium falciparum and dengue co-infection
in a 6 months pregnancy.
AB - India being a tropical country, parasitic infections especially with Plasmodium
species are very common in this region. The present case report is that of
Plasmodium vivax, Plasmodium falciparum and dengue co-infection in a 6 months
pregnant lady who was timely diagnosed and appropriately treated followed by a
complete recovery along with feto-maternal well-being.
PMID- 24349839
TI - Rectal lipoma associated with genital prolapse.
AB - Lipomas are the tumors of mature lipocytes with its occurrence most often on the
torso, neck, upper thighs, upper arms, and armpits, but they can occur almost
anywhere in the body. They are the rare tumors of intestine, more frequently
located in large intestine compared to small intestine. We present the case of a
58-year-old post-menopausal lady presenting with rectal bleeding and utero
vaginal prolapse. The prolapsing mass was excised, and histopathological
examination diagnosed the lesion to be a lipoma.
PMID- 24349840
TI - Sternal tuberculosis.
AB - Extra-pulmonary tuberculosis constitutes 15-20% of total tuberculosis (TB) case
load in immuno-competent patients. Affliction of the skeletal system is rare with
still rarer presentation of sternal osteomyelitis even in endemic countries. A
patient with primary sternal TB presenting with multiple cutaneous sinuses over
the anterior chest wall is being reported. A high element of suspicion is needed
more so in resource limited setting for early diagnosis and treatment.
PMID- 24349841
TI - Superior mesenteric artery syndrome: an uncommon cause of abdominal pain
mimicking gastric outlet obstruction.
AB - Upper gastrointestinal symptoms like vomiting, abdominal pain, abdominal
distention may be caused by many conditions like complicated peptic/duodenal
ulcer, gastritis or hiatal hernia. However, these symptoms are uncommonly
produced by superior mesenteric artery (SMA) syndrome. SMA syndrome is triggered
when there is narrowing of the mesenteric angle and shortening of the
aortomesenteric distance. We report a case of 42-year-old female who presented
with features of gastric outlet obstruction which on further investigation was
revealed as SMA syndrome. The aetiology, presentation, diagnosis and management
of this unusual condition are discussed.
PMID- 24349842
TI - Pediatric stroke: neurological sequelae in uncorrected tetralogy of fallot.
AB - Pediatric stroke is an uncommon entity. A risk factor is present in almost half
of the children at the time of stroke. The most common cause of stroke in
children is probably congenital heart disease. Other risk factors include sickle
cell disease, infections, and various prothrombotic conditions. We present a case
of a 3-year-old male child, who was previously diagnosed with Tetralogy of Fallot
and presented with left-sided weakness and one episode of generalized tonic
clonic seizures.
PMID- 24349843
TI - Familial dermal eccrine cylindromatosis with emphasis on histology and genetic
mapping.
AB - Familial cylindromatosis (FC) is an autosomal dominant disorder with apparently
complete penetrance, but variable expression. There is an increasing evidence
that FC is clinically, genetically, and histologically heterogeneous disorder as
the simultaneous occurrence of cylindromas and other tumors of skin appendages
within the affected individuals and families. The presence of multiple scalp
cylindromas is often associated with autosomal dominant Brooke-Spielger syndrome,
a condition in which there are co-existent facial trichoepitheliomas and
spiradenomas. We present here a case of multiple cylindromatosis in a family
affecting many members successively.
PMID- 24349844
TI - Burn injury caused by laptop computers.
AB - Laptop burn is a real condition and medical reports indicate that using a laptop
across the legs can indeed cause it. in very rare cases, the condition can cause
damage leading to skin cancer. A 24-year-old man presented with an asymptomatic
reddish brown pigmentation on the thighs. After an extensive work-up, burning
caused by use of a laptop was observed. Burning was induced in 3 days by using
laptop for 4 h daily. Laptop should be used in properly ventilated and air
conditioned rooms. The most effective way of preventing erythema is to use the
laptop on the table or desk.
PMID- 24349845
TI - Cellular schwannoma arising from sigmoid mesocolon presenting as torsion.
AB - Schwannomas are a type of peripheral nerve sheath tumors with clinically indolent
behavior. Though, they can occur anywhere in body, the incidence in
retroperitoneum, mediastinum, and pelvis is exceedingly rare. We present a case
of a 58-year-old female with a massive twisted tumor arising from sigmoid
mesocolon. The tumor was diagnosed to be a case of cellular schwannoma, an
exceedingly rare tumor in this location with rare presentation.
PMID- 24349846
TI - Primary neuroendocrine carcinoma of breast: a rare case report.
AB - Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic
entity till recently due its rare incidence and lack of definitive criteria for
diagnosis. We present a case of PNEC of breast in a middle aged lady. A 34 years
lady presented with a breast lump since 1 month, who underwent modified radical
mastectomy with axillary clearance. Histopathological diagnoses were infiltrating
ductal carcinoma-neuroendocrine (NE) type. Immunohistochemistry showed estrogen,
progesterone positivity and NE markers positivity in more than 50% of tumor cells
for chromogranin, synaptophysin, neuron specific enolase. On further
investigation by whole body computed tomography and magnetic resonance imaging
revealed no extra mammary primary tumor. Hence the diagnosis of PNEC of breast
was confirmed. Patient received chemo and hormonal therapy and doing well after 6
months of follow up.
PMID- 24349847
TI - Periapical infection masquerading as a nasal pustule.
AB - Periapical infections may give rise to intraoral and extraoral complications.
Extraoral manifestation of periapical infection without an accompanying dental
symptom may lead to presentation first to Medical doctor. This is a case of
pulpal necrosis of right maxillary central incisor (tooth #11) with a discharging
sinus, in the floor of the right nostril. Failure to associate the discolored
tooth #11 and a discharging sinus in the floor of the right nostril, lead to the
initial presentation of the patient to the Otorhinolaryngologist. The recurrent
discharge from the sinus continued despite prolonged antibiotics administration.
This case report showed that extraoral sinus tract of dental origin in the
nostril poses a diagnostic challenge. It is expected to raise awareness of
clinicians about the unusual presentations of periapical infection. There is a
need for examination of the maxillary incisors in patients presenting with nasal
pustule.
PMID- 24349848
TI - Typhoid intestinal perforation: 24 perforations in one patient.
AB - Intestine perforation is one of the most dreaded and common complication of
typhoid fever remarkably so in developing world; it usually leads to diffuse
peritonitis, requiring early surgical intervention. Despite various measures such
as safe drinking water supply and safe disposal of waste, intestinal perforation
from salmonellosis remains the most common emergency surgery performed. The
incidence continues to rise, so also the mortality, despite new antibiotics and
improvement in surgical technique. More disturbing is that we now see increasing
number of ileal perforations and colonic involvement. We hereby present a case
report of 35-year-old male with multiple (24) intestinal perforation in the Ileum
and Cecum.
PMID- 24349849
TI - Progressive supranuclear palsy misdiagnosed as Parkinson's disease: a case report
and review of literature.
AB - Because of its increasingly recognized clinical diversity, progressive
supranuclear palsy (PSP) may be difficult to diagnose, particularly in resource
poor settings where the means of getting supportive tests is a huge challenge.
This often results in underdiagnosis or misdiagnosis of PSP, most commonly as
Parkinson's disease. The author reported a case of how brain magnetic resonance
imaging (MRI) was used to arrive at the diagnosis of PSP in a man previously
misdiagnosed as Parkinson's disease. Relevant literatures regarding the
diagnostic utility of MRI in PSP were also reviewed.
PMID- 24349850
TI - Xanthogranulomatous endometritis: an unusual pathological entity mimicking
endometrial carcinoma.
AB - Xanthogranulomatous endometritis is an unusual pathological entity mimicking
endometrial carcinoma. This shows sheets of foamy histiocytes alongwith other
inflammatory cells. We, hereby, report a case of 45 year multigravida female with
irregular menstrual history, clinically diagnosed as carcinoma and
histopathologically turned out as xanthogranulomatous endometritis. So, this
condition should always be dealt with caution, and pathologists and clinicians
should be aware of it.
PMID- 24349851
TI - Acute pancreatitis associated with elevated troponin levels: whether to
thrombolyse or not?
AB - The presentation of retrosternal chest pain with normal electrocardiogram (ECG)
during chest pain followed by initial presentation of acute pancreatitis can lead
to a dilemma in managing such a patient, and whether to thrombolyse such a
patient is a real controversy. We hereby present a similar case who was diagnosed
to be having acute pancreatitis on admission, on clinical grounds, confirmed by
laboratory investigations and ultrasonography, who subsequently developed
retrosternal chest pain with normal ECG during the chest pain. All further serial
ECGs after the onset of chest pain were within normal limits. The troponin-I
level of this patient was positive twice (done 16 h apart). The patient was
treated as acute coronary syndrome along with the standard management protocol of
acute pancreatitis.
PMID- 24349852
TI - Silver: russell syndrome with cryptorchidism.
PMID- 24349853
TI - Reasons for Non-compliance of Patients to Attend Referral Hospital After
Screening for Oral Pre-cancer Lesions through Camp Approach in Rural Population
of Indiaa.
PMID- 24349854
TI - Schedule H1: Is it a Solution to Curve Antimicrobial Misuse in India?
PMID- 24349855
TI - Plagiarism: trespassing the grey zone between searching and researching.
PMID- 24349856
TI - Assessing the Usefulness of Salivary Gland Fine Needle Aspiration Cytology as
Diagnostic Aid for Salivary gland Malignancy.
PMID- 24349857
TI - A comment on assessment of mild cognitive impairment with mini mental state
examination among adults in southeast Nigeria.
PMID- 24349858
TI - Author's response.
PMID- 24349859
TI - Is Mind-Body Relaxation By Yoga is Effective to Combat with Lifestyle Stress?
PMID- 24349860
TI - An extensive denture-induced hyperplasia of maxilla.
AB - Denture-induced hyperplasia is a reactive lesion arising from excessive and
chronic mechanical pressure on the vestibular oral mucosa. It has a female
predilection and it is mostly seen in the maxilla. The size of the lesion may be
as small as a few millimeters to massive lesion involving the entire vestibule.
It is usually asymptomatic but sometimes severe inflammation and ulceration can
occur. Elimination of the inflammation and excision of the lesion is the
treatment of choice. Denture induced hyperplasia in right maxillary buccal
vestibule in a middle age old female patient was presented. Surgical excision was
done and new denture was fabricated.
PMID- 24349861
TI - Enthesitis is an Extraintestinal Manifestation of Pediatric Inflammatory Bowel
Disease.
AB - BACKGROUND: Enthesitis is an extra-intestinal manifestation of inflammatory bowel
disease (IBD) in adults. However, little has been published about the prevalence
or characteristics of enthesitis in pediatric IBD. METHODS: We conducted a cross
sectional study of children and young adults ages 4-21 years with IBD. Subjects
were recruited among those receiving routine care in a gastroenterology clinic.
All subjects underwent a clinical examination of the entheses and joints, and
completed a study questionnaire. RESULTS: We enrolled 43 subjects, who had a
median age of 16 years and a median time from IBD diagnosis of 2.7 years. 32
subjects (74%) had Crohn disease, 10 subjects (23%) had indeterminate colitis,
and 1 subject (2%) had ulcerative colitis. At least one tender enthesis was
present in 21% of subjects and 12% had more than 2 tender entheses. The most
commonly affected entheses were located at the inferior patella, the femoral
greater trochanter, and the proximal humerus. The presence of enthesitis was
associated with a higher intensity of recent musculoskeletal pain (p=0.03).
CONCLUSIONS: Enthesitis is a prevalent extra-intestinal manifestation of
pediatric IBD and is associated with increased musculoskeletal pain. Future
studies should evaluate the functional and long-term impact of enthesitis on
children with IBD.
PMID- 24349862
TI - Adverse Experiences and Suicidal Ideation in Adolescence: Exploring the Link
Using the LONGSCAN Samples.
AB - OBJECTIVE: Although widely studied in adults, the link between lifetime
adversities and suicidal ideation in youth is poorly understood. The purpose of
this study was to explore this link in adolescents. METHODS: The analyses used a
sample of 740 16-year-old youth in the LONGSCAN sample, and distinguished between
childhood (before the age of 12) and adolescent (between age 12 and age 16)
adversities. RESULTS: There was a significant link between cumulative lifetime
adversities and suicidal ideation. There was no evidence that this link was
moderated by gender. Childhood adversities moderated the effects of adolescent
adversities on suicidal ideation; effects of adolescent adversities were
strongest at low levels of childhood adversities. There was also some evidence
supporting a specific cumulative model of the effects of adversities on suicidal
ideation; the most predictive model included the sum of the following
adversities: childhood physical abuse, childhood neglect, childhood family
violence, childhood residential instability, adolescent physical abuse,
adolescent sexual abuse, adolescent psychological maltreatment, and adolescent
community violence. CONCLUSION: The timing and nature of adversities are
important in understanding youth suicidal ideation risk; in particular,
adolescent maltreatment and community violence appear to be strong predictors.
Preventing and appropriately responding to the abuse of adolescents has the
potential to reduce the risk of suicidal ideation.
PMID- 24349863
TI - IS IT THE EXCEPTION OR THE RULE? DAILY CO-OCCURRENCE OF PHYSICAL, SEXUAL, AND
PSYCHOLOGICAL PARTNER VIOLENCE IN A 90-DAY STUDY OF SUBSTANCE-USING, COMMUNITY
WOMEN.
AB - OBJECTIVE: This study aims to describe the daily co-occurrence of physical,
sexual, and psychological intimate partner violence (IPV) among substance-using,
community-based women currently experiencing IPV. METHODS: A micro-longitudinal
study design was used to collect data daily from 49 women for 90 days. RESULTS:
On the majority of days (62%), no IPV occurred; 27% of days were characterized by
psychological IPV alone, followed by the co-occurrence of psychological and
physical IPV (6% of IPV days). Results of person-level analyses showed comparable
sized correlations between the proportion of days with physical and sexual IPV
and the proportion of days with physical and psychological IPV. However, results
of day-level analyses revealed that the association between physical and
psychological IPV was much stronger than the association between physical and
sexual IPV; Physical IPV was 64 times more likely to occur on days when
psychological IPV occurred. CONCLUSIONS: Results revealed new information about
physical, sexual, and psychological IPV experiences and demonstrate the utility
of a micro-longitudinal design among this high risk population. Implications for
practice, future research, and the development of preventive interventions are
noted, underscoring the importance of psychological IPV and the range of IPV
experiences among women.
PMID- 24349865
TI - Clinical functional anatomy of the pterygopalatine ganglion, cephalgia and
related dysautonomias: A review.
AB - The purpose of this article is to explain the anatomy of the pterygopalatine
ganglion (PPG), its location in the pterygopalatine fossa (PPF) in the skull, and
the relationship it has to the Vidian nerve terminal branches and the fifth
cranial nerve. An overview of the neuro-anatomical/clinical correlations, a
spectrum of pathologies affecting the seventh cranial nerve and some therapies
both medical and surgical are noted. The focus is the pterygopalatine region with
discussion of the proximal courses of the seventh and fifth cranial nerves and
their pathological processes. The ganglion is used as an example of neuro
anatomical model for explaining cluster headaches (CH). Radiological correlation
is included to clarify the location of the PPF and its clinical importance.
PMID- 24349864
TI - Minimally invasive management of adult craniopharyngiomas: An analysis of our
series and review of literature.
AB - BACKGROUND: Craniopharyngiomas (CPs) are slow growing tumors with an incidence of
between 1.2% and 4.6%, having a bimodal age distribution typically peaking in
childhood and in adults between 45 and 60 years. Recurrences occur even after
documented gross total resections necessitating a combination of therapeutic
strategies. Obtaining a cure of this tumor in adults without producing major side
effects continues to remain elusive. METHODS: We describe our results in 11
patients with CP treated in a minimally invasive fashion using a combination of
techniques like burr hole aspiration, Ommaya reservoir placement, ventriculo
peritoneal (VP) shunting and focal radiation (Gamma Knife stereotactic
radiosurgery/Intensity modulated radiotherapy [GKRS/IMRT]). RESULTS: Visual
function remained intact in all patients; endocrine status remained stable with
two patients developing new postoperative diabetes insipidus. There was no
periprocedural morbidity or mortality, with hospital stays for any in-patient
procedure being 48 hours or less. CONCLUSIONS: Minimally invasive techniques such
as cyst aspiration, insertion of a catheter with Ommaya reservoir, when combined
with stereotactic radiosurgery/IMRT is an effective and safe option for
management and long-term control of adult CPs. We believe the Ommaya catheter by
itself could act as a stent, creating a tract allowing gradual drainage of cyst
fluid and stabilization without necessitating any further interventions in
selected cases.
PMID- 24349866
TI - Stereotactic radiosurgery for the treatment of Glomus Jugulare Tumors.
AB - BACKGROUND: The glomus jugulare tumor is a slowly growing benign neoplasm
originating from neural crest. There is a high morbidity associated with surgical
resection of glomus jugulare. Radiosurgery play a relevant role as a therapeutic
option in these tumors and its use has grown in popularity. The authors describe
a retrospective series of 15 patients and reviewed the literature about the
glomus jugulare tumors. METHODS: We reviewed retrospectively the data of 15
patients treated with stereotactic linear accelerator stereotactic radiosurgery
(LINAC) radiosurgery between 2006 and 2011. RESULTS: The average tumor volume was
18.5 cm(3). The radiation dose to the tumor margin ranged between 12 and 20 Gy.
The neurological status improved in three patients and remained unchanged in 12
patients. One patient developed a transient 7(th) nerve palsy that improved after
clinical treatment. All tumors remained stable in size on follow-up with
resonance magnetic images. CONCLUSIONS: The radiosurgery is a safe and effective
therapy for patients with glomus jugulare tumor. Despite the short follow-up
period and the limited number of patients analyzed, we can infer that
radiosurgery produce a tumor growth control with low morbidity, and may be used
as a good option to surgical resection in selected cases.
PMID- 24349867
TI - Stereotactic radiosurgery boost to the resection cavity for cerebral metastases:
Report of overall survival, complications, and corticosteroid protocol.
AB - BACKGROUND: This report focuses on the overall survival and complications
associated with treatment of cerebral metastases with surgical resection followed
by stereotactic radiosurgery (SRS). Management and complications of
corticosteroid therapy are underreported in the literature but represent an
important source of morbidity for patients. METHODS: Fifty-nine consecutive
patients underwent surgical resection of a cerebral metastasis followed by SRS to
the cavity. Patient charts were reviewed retrospectively to ascertain overall
survival, local control, surgical complications, SRS complications, and
corticosteroid complications. RESULTS: Our mean follow-up was 14.4 months (median
12.0 months, range 0.9-62.9 months). Median overall survival in this series was
15.25 months and local control was 98.3%. There was a statistically significant
survival benefit conferred by Radiation Therapy Oncology Group recursive
partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8%
while the SRS complication rate was 2.4%. Corticosteroid complications are
reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%,
and at 12 months no patients remained on corticosteroid therapy. CONCLUSIONS:
Overall survival and local control with this treatment paradigm compare well to
the other published literature. Complications associated with this patient
population are low. A corticosteroid tapering protocol is proposed and
demonstrated lower rates of steroid-related complications and dependence than
previously reported.
PMID- 24349868
TI - Neuropsychological effects of deep brain stimulation for Parkinson's disease.
AB - BACKGROUND: Putative changes of cognition after deep brain stimulation (DBS) in
patients with Parkinson's disease (PD) are a matter of debate. The aim of this
study was to assess cognitive abilities before and following bilateral
subthalamic nucleus (STN) DBS and to review the available literature. METHODS:
Twenty patients underwent bilateral DBS of the STN. Cognitive skills were
assessed in a standardized fashion before and at least at 12 months after the
surgical intervention. RESULTS: There was a significant decline of both semantic
and phonematic verbal fluency and a mild trend for a deterioration of verbal
memory after DBS. Mood, general cognitive screening, and visospatial abilities
remained unchanged. CONCLUSION: STN DBS in the treatment of PD has resulted in a
significant reduction of motor symptoms and improved independence and quality of
life in appropriately selected patients. However, it may have isolatable effects
on verbal fluency and related function. Case series in the literature reported
similar findings. Potential candidates for DBS should be counseled about the risk
of mild cognitive declines.
PMID- 24349869
TI - Image guided surgery in the management of craniocerebral gunshot injuries.
AB - BACKGROUND: A craniocerebral trauma caused by firearms is a complex injury with
high morbidity and mortality. One of the most intriguing and controversial part
in their management in salvageable patients is the decision to remove the
bullet/pellet. A bullet is foreign to the brain and, in principle, should be
removed. Surgical options for bullet extraction span from conventional
craniotomy, through C-arm-guided surgery to minimally invasive frame or frameless
stereotaxy. But what is the best surgical option? METHODS: We prospectively
followed up a cohort of 28 patients with cranio-cerebral gunshot injury (CCHSI)
managed from January to December 2012 in our department of neurosurgery. The
missiles were extracted via stereotaxy (frame or frameless), C-arm-guided, or
free-hand-based surgery. Cases managed conservatively were excluded. The Glasgow
Outcome Score was used to assess the functional outcome on discharge. RESULTS:
Five of the eight "stereotactic cases" had an excellent outcome after missile
extraction while the initially planned stereotaxy missed locating the missile in
three cases and were thus subjected to free hand craniotomy. Excellent outcome
was obtained in five of the nine "neuronavigation cases, five of the eight cases
for free hand surgery based on the bony landmarks, and five of the six C-arm
based surgery. CONCLUSION: Conventional craniotomy isn't indicated in the
extraction of isolated, retained, intracranial firearm missiles in civilian
injury but could be useful when the missile is incorporated within a surgical
lesion. Stereotactic surgery could be useful for bullet extraction, though with
limited precision in identifying small pellets because of their small sizes, thus
exposing patients to same risk of brain insult when retrieving a missile by
conventional surgery. Because of its availability, C-arm-guided surgery continues
to be of much benefit, especially in emergency situations. We recommend an
extensive long-term study of these treatment modalities for CCGSI.
PMID- 24349870
TI - Management of trigeminal neuralgia in sclerosteosis.
AB - BACKGROUND: Sclerosteosis is a rare bone disorder characterized by a progressive
craniotubular hyperostosis. The diagnosis of sclerosteosis is based on
characteristic clinical and radiographic features and a family history consistent
with autosomal recessive inheritance. The skull overgrowth may lead to lethal
elevation of intracranial pressure, distortion of the face, and entrapment of
cranial nerves, resulting in recurrent facial palsy or secondary trigeminal
neuralgia. CASES DESCRIPTION: The authors reported cases of two siblings who were
diagnosed with familial sclerosteosis and presented with secondary trigeminal
neuralgia. The patients were 28 and 40-year-old and presented with pain in the
right V2-V3 and V3 distributions, respectively. The facial pain was resistant to
medications and was treated with percutaneous techniques. The foramen ovale
puncture was complicated initially and the difficulty increased over the years
due to stenosis of the foramen. CONCLUSION: The treatment of the trigeminal
neuralgia secondary to hyperostosis and resistant to medications presents a
dilemma. The narrowing of the foramen oval and difficulty in the identifying and
approaching of the foramen makes the percutaneous technique a challenge for the
neurosurgeon in patients harboring sclerosteosis. Microvascular decompression
should not be considered since the primary cause of the trigeminal neuralgia is
the nerve entrapment by the narrowing of neurovascular foramina and not the
neurovascular conflict related to essential trigeminal neuralgia. Stereotactic
radiosurgery may be a good treatment option, but there is a lack of published
data supporting the use of this method in cranial hyperostosis.
PMID- 24349871
TI - Dynamic Stress Factor (DySF): A Significant Predictor of Severe Hypoglycemic
Events in Children with Type 1 Diabetes.
AB - Hemoglobin A1c (HbA1c) is the current standard used in the clinical treatment of
patients with diabetes. However, it has been shown that patients with similar
HbA1c values may have widely different fluctuations in blood glucose values over
the same period of time, including time spent in hyper- and/or hypo-glycemia.
Hence, there exists a need for quantitative measures that can supplement HbA1c in
managing patients with diabetes. We introduce and compare the Dynamic Stress
Factor, DySF, a newly developed metric that quantifies glycemic volatility based
on patient-specific glucose transition density profiles with HbA1c and with
currently used glucose variability metrics in predicting severe hypoglycemia in
children with type 1 diabetes. DySF, the daily weighted number of large monotonic
glycemic transitions that occur within one hour, was calculated for 441 total
subjects with type 1 diabetes (146 children, aged 8-14 yrs) to assess the
magnitude and frequency of glucose transitions per day. Severe hypoglycemic
episodes (HE) were quantified for all subjects and evaluated against HbA1c and
existing measures of glucose variability, including SD, MAGE, MODD, and CONGA
using logistic regression models. DySF was found to be a predictor of severe HE
in children (p = 0.018) with the likelihood of a child, aged 8-14 yrs,
experiencing severe hypoglycemia increasing by up to 20% with decreasing values
of up to 60% of DySF. Patients of any age who had one or multiple severe
hypoglycemic episodes had on average a lower DySF when compared to those with no
HE. Additionally, when considering mean glucose levels, DySF/mean was a
preliminary predictor of severe HE in patients with HbA1c <= 6.5% (p = 0.062).
DySF is a dynamic, quantitative, measure of daily glucose "volatility" that
separates patients, within the same strata of HbA1c, into visually distinct
patient profiles. DySF can be used as a preliminary predictor of clinically
severe hypoglycemia in children and "well-controlled" patients with HbA1c <=
6.5%.
PMID- 24349872
TI - Critical Factors in Measuring Angiogenesis Using the Aortic Ring Model.
AB - Angiogenesis is a feature of numerous pathologies including cancer and
inflammatory conditions and as such is key therapeutic target for the treatment
of disorders where excessive or insufficient formation of new blood vessels
occurs. The study of angiogenesis in vivo provides many challenges, however the
growth of new blood vessels in vitro from aortic explants has provided a highly
useful model for the study of this process. In this manuscript we examine the
critical factors which can affect this assay and demonstrate that aortas from
both female rats and mice exhibit a reduced angiogenic response to males. These
findings have implications not only for the experimental design of angiogenesis
experiments but also in the use of therapies targeting angiogenesis in the
treatment of pathologies, such as cancer.
PMID- 24349873
TI - Effects of Cyclic vs. Acyclic Hydrophobic Subunits on the Chemical Structure and
Biological Properties of Nylon-3 Co-Polymers.
AB - Nylon-3 co-polymers containing both hydrophobic and cationic subunits can mimic
the activity profile of host-defense peptides, if subunit identity and proportion
are carefully selected. These sequence- and stereo-random co-polymers inhibit
bacterial growth at relatively low concentrations, apparently via disruption of
bacterial membranes, but they are relatively non-disruptive toward eukaryotic
cell membranes (low hemolytic activity). In all previous examples, the
hydrophobic subunits have contained cycloalkyl groups that incorporate the
backbone Calpha-Cbeta bond. Here we have explored the effects of using analogous
acyclic hydrophobic subunits. The results indicate that the replacing cyclic with
acyclic hydrophobic subunits has a modest influence on biological properties.
This influence appears to arise from differences in subunit flexibility.
PMID- 24349874
TI - Clinical response of advanced cancer patients to cellular immunotherapy and
intensity-modulated radiation therapy.
AB - Patients afflicted with advanced cancers were treated with the intratumoral
injection of autologous immature dendritic cells (iDCs) followed by activated T
cell infusion and intensity-modulated radiation therapy (IMRT). A second round of
iDCs and activated T cells was then administered to patients after the last
radiation cycle. This complete regimen was repeated for new and recurring lesions
after 6 weeks of follow-up. One year post therapy, outcome analyses were
performed to evaluate treatment efficacy. Patients were grouped according to both
the number and size of tumors and clinical parameters at treatment initiation,
including recurrent disease after standard cancer therapy, Stage IV disease, and
no prior therapy. Irrespective of prior treatment status, 23/37 patients with <=
5 neoplastic lesions that were <= 3 cm in diameter achieved complete responses
(CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals
harboring larger and more numerous lesions, CRs were observed in 7/74 patients
that had received prior SCT and in 2/56 previously untreated patients. Some
patients manifested immune responses including an increase in CD8+CD56+
lymphocytes among circulating mononuclear cells in the course of treatment. To
prospectively explore the therapeutic use of these cells, CD8+ cells were
isolated from patients that had been treated with cellular immunotherapy and
IMRT, expanded in vitro, and injected into recurrent metastatic sites in 13
individuals who underwent the same immunoradiotherapeutic regimens but failed to
respond. CRs were achieved in 34 of 58 of such recurrent lesions while PRs in 17
of 58. These data support the expanded use of immunoradiotherapy in advanced
cancer patients exhibiting progressive disease.
PMID- 24349875
TI - HLA-DR expression on myeloid cells is a potential prognostic factor in patients
with high-risk neuroblastoma.
AB - The adaptive immune system has been reported to play a dual role in many cancers,
on one hand inhibiting tumor growth and, on the other hand, promoting disease
progression, escape from cancer immunosurveillance and relapse. We have
previously reported that the suppression of the adaptive immune response
associated with high levels of myeloid-derived suppressor cells (MDSC) was
evident in patients with low-risk neuroblastoma. Here, we report the results of a
pilot study demonstrating that the amounts of HLA-DR-positive or negative myeloid
cells in the peripheral blood might predict disease outcome among individuals
affected by high-risk neuroblastoma.
PMID- 24349876
TI - Antitumor activity of an immunocytokine composed of an anti-GD2 antibody and the
IL-15 superagonist RLI.
AB - The use of interleukin (IL)-15 or the IL-15 superagonist RLI as immunological
adjuvants presents many advantages over that of IL-2, including a reduced
toxicity and an improved efficacy. We have generated an immunocytokine that
specifically targets RLI to a tumor-associated antigen, namely,
disialoganglioside GD2. This agent displayed robust antitumor activity in 2
syngeneic murine models of malignant disease.
PMID- 24349878
TI - Cardiac Hegemony of Senescence.
AB - Cardiac senescence and age-related disease development have gained general
attention and recognition in the past decades due to increased accessibility and
quality of health care. The advancement in global civilization is complementary
to concerns regarding population aging and development of chronic degenerative
diseases. Cardiac degeneration has been rigorously studied. The molecular
mechanisms of cardiac senescence are on multiple cellular levels and hold a
multilayer complexity level, thereby hampering development of unambiguous
treatment protocols. In particular, the synergistic exchange of the senescence
phenotype through a senescence secretome between myocytes and stem cells appears
complicated and is of great future therapeutic value. The current review article
will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence,
and the mutual exchange of senescent secretome. Future cardiac cell therapy
approaches require a comprehensive understanding of myocardial senescence to
improve therapeutic efficiency as well as efficacy.
PMID- 24349877
TI - RELATIONSHIP OF GAIT AND COGNITION IN THE ELDERLY.
AB - Gait and cognitive impairments in older adults mostly reflect the co-occurrence
of two geriatric syndromes linked by common underlying brain substrates and
pathologies. Gait control is predominately mediated by frontal subcortical
circuits, which overlap with circuits controlling executive control and attention
functions. These circuits are vulnerable to multiple age-related pathologies such
as ischemia, inflammation, and neurodegeneration, which could ultimately cause
cognitive, gait, or combined cognitive and gait impairments. The following review
aims to describe various gait and cognitive classifications, gait based
phenotypes, common underlying pathological processes, and provide a link between
motor and cognitive impairments in an effort to predict the risk of dementia, as
well as remediate impairments by applying appropriate interventions.
PMID- 24349879
TI - "It takes a village" to raise research productivity: Impact of a Trauma
Interdisciplinary Group for Research (TIGR) at an urban, Level 1 trauma center.
AB - BACKGROUND: Few interdisciplinary research groups include basic scientists,
pharmacists, therapists, nutritionists, lab technicians, as well as trauma
patients and families, in addition to clinicians. Increasing interprofessional
diversity within scientific teams working to improve trauma care is a goal of
national organizations and federal funding agencies like the National Institutes
of Health (NIH). This paper describes the design, implementation, and outcomes of
a Trauma Interdisciplinary Group for Research (TIGR) at a Level 1 trauma center
as it relates to increasing research productivity, with specific examples
excerpted from an on-going NIH-funded study. METHODS: We utilized a pre-test/post
test design with objectives aimed at measuring increases in research productivity
following a targeted intervention. A SWOT (strengths, weaknesses, opportunities,
threats) analysis was used to develop the intervention which included research
skill-building activities, accomplished by adding multidisciplinary investigators
to an existing NIH-funded project. The NIH project aimed to test the hypothesis
that accelerated biologic aging from chronic stress increases baseline
inflammation and reduces inflammatory response to trauma (projected N=150).
Pre/Post-TIGR data related to participant screening, recruitment, consent, and
research processes were compared. Research productivity was measured through
abstracts, publications, and investigator-initiated projects. RESULTS: Research
products increased from N =12 to N=42; (~ 400%). Research proposals for federal
funding increased from N=0 to N=3, with success rate of 66%. Participant
screenings for the NIH-funded study increased from N=40 to N=313. Consents
increased from N=14 to N=70. Lab service fees were reduced from $300/participant
to $5/participant. CONCLUSIONS: Adding diversity to our scientific team via TIGR
was exponentially successful in 1) improving research productivity, 2) reducing
research costs, and 3) increasing research products and mentoring activities that
the team prior to TIGR had not entertained. The team is now well-positioned to
apply for more federally funded projects and more trauma clinicians are
considering research careers than before.
PMID- 24349880
TI - Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex
Mites.
AB - PURPOSE: To determine the active ingredient in tea tree oil (TTO) responsible for
its reported killing effect on Demodex mites, the most common ectoparasite found
in the human skin extending to the eye. METHODS: Using a reported in vitro
killing assay to measure the survival time of adult Demodex folliculorum up to
150 minutes, we have screened serial concentrations of 13 of the 15 known
ingredients of TTO (ISO4730:2004) that were soluble in mineral oil and examined
their synergistic relationships in killing mites. The most potent ingredient was
then tested for its efficacy in killing Demodex in vivo. RESULTS: All ingredients
exhibited a dose-dependent killing effect. Besides Terpinen-4-ol, the order of
relative potency did not correlate with the order of relative abundance in TTO
for the remaining 12 ingredients. Terpinen-4-ol was the most potent ingredient
followed by alpha-Terpineol, 1,8-Cineole and Sabinene. Terpinen-4-ol, the most
abundant ingredient in TTO, was more potent than TTO at equivalent concentrations
and its killing effect was even observable at a mere concentration of 1%.
Terpinen-4-ol exhibited a significant synergistic effect with Terpinolene, but an
antagonistic effect with alpha-Terpineol in killing mites (both P < 0.05). In
vivo, Terpinen-4-ol was shown to eradicate mites. CONCLUSIONS: The above finding
suggests that deployment of Terpinen-4-ol alone should enhance its potency in
killing Demodex mites by reducing the adverse and antagonistic effects from other
ingredients in TTO. TRANSLATIONAL RELEVANCE: Terpinen-4-ol can be adopted in
future formulations of acaricides to treat a number of ocular and cutaneous
diseases caused by demodicosis.
PMID- 24349881
TI - Validity and Repeatability of Saccadic Response Times Across the Visual Field in
Eye Movement Perimetry.
AB - PURPOSE: To assess the validity and repeatability of saccadic reaction times
(SRT) across the visual field up to 30 degrees using eye movement perimetry
(EMP). METHODS: Eighteen subjects (36 eyes) were shown a central stimulus on a
flat monitor screen. Next, peripheral stimuli were shown using an overlap
paradigm. Subjects were instructed to look at detected peripheral stimuli and
then refixate the central stimulus again. In three repetitive measurement series,
a total of 288 visual stimuli (3 series * 24 locations * 4 contrast levels) were
presented. Levene's test for equality of variances was applied to test the effect
of stimulus location and measurement series on SRT variance. A Wilcoxon signed
ranks test was used to compare SRTs between measurement series. RESULTS: A total
of 26 eyes were included in the study (72%). On average, 90.5% of the peripheral
stimuli were labeled as 'seen' based on eye movement responses. Between the
series, the mean SD of SRT differences was approximately 100 ms. Significantly
faster SRTs were only found at contrast level 0.8 in series III compared with
series II. In series I, SRT variance was independent in 75% of all locations.
Across the three series, SRT variance was independent in 87.5% of all locations.
CONCLUSIONS: The present study demonstrates low variability of SRT across the
visual field up to 30 degrees eccentricity and across measurement series.
TRANSLATIONAL RELEVANCE: SRT as a measure for visual field responsiveness may be
a potential marker to detect risk areas in specific parts of the visual field.
PMID- 24349882
TI - Proceedings of the First International Optogenetic Therapies for Vision
Symposium.
AB - Optogenetics is a research field that uses gene therapy to deliver a gene
encoding a light-activated protein to cells providing light-regulated control of
targeted cell pathways. The technology is a popular tool in many fields of
neuroscience, used to transiently switch cells on and off, for example, to map
neural circuits. In inherited retinal degenerative diseases, where loss of vision
results from the loss of photoreceptors, optogenetics can be applied to either
augment the function of surviving photoreceptors or confer light sensitivity to
naturally nonlight sensitive retinal cells, such as a bipolar cells. This can be
achieved either by the light sensitive protein integrating with native internal
signaling pathways, or by using a dual function membrane protein that integrates
light signaling with an ion channel or pump activity. Exposing treated cells to
light of the correct wavelength activates the protein, resulting in cellular
depolarization or hyperpolarization that triggers neurological signaling to the
visual cortex. While there is a lot of interest in optogenetics as a pan-disease
clinical treatment for end-stage application in the inherited degenerative
diseases of the retina, research to date has been limited to nonhuman clinical
studies. To address the clinical translational needs of this technology, the
Foundation Fighting Blindness and Massachusetts Eye and Ear Infirmary cohosted an
International Optogenetic Therapies for Vision Workshop, which was held at
Massachusetts Eye and Ear Infirmary, Boston, Massachusetts on June 1, 2012.
PMID- 24349883
TI - A Comparison of Methods for Tracking Progression in X-Linked Retinitis Pigmentosa
Using Frequency Domain OCT.
AB - PURPOSE: To compare the efficacy of frequency domain optical coherence tomography
(fdOCT)-derived outer retinal measures in tracking disease progression in x
linked (xl) retinitis pigmentosa (RP) patients. METHODS: Macular volume scans and
line scans (Spectralis) were obtained from 27 xlRP patients (15.3 +/- 6.4 years)
at two visits approximately 2 years apart. Changes in average outer retinal layer
thicknesses across the volume scan were compared to changes detected by measures
derived from the edge of the inner segment ellipsoid zone (EZ) band, that is,
where the EZ band (also known as inner segment/outer segment border) disappears.
Repeatability was tested on an independent set of 18 RP patients (43.5 +/- 18.0
years). RESULTS: Average outer segment (OS) and outer nuclear layer (ONL)
thickness showed marginally significant annual changes (P < 0.05), while total
receptor (TR) thickness showed a greater change (P < 0.01). All measures derived
from the edge of the EZ band significantly decreased (P < 0.01). Mean +/- SD for
test-retest differences in horizontal widths was 0.01 +/- 0.06 mm. CONCLUSIONS:
Measures of the EZ band are more effective in detecting disease progression than
are thickness measures. Given the similar effectiveness of line and volume scans,
manually marking the EZ band edge on vertical and/or horizontal line scans can be
useful in tracking progression. TRANSLATIONAL RELEVANCE: Because disease
progression in RP can be relatively slow, annual changes can be difficult to
monitor during the course of a clinical trial. Here we suggest a quick,
effective, and reliable method for detecting subtle changes.
PMID- 24349884
TI - The Biomechanical Effect of Corneal Collagen Cross-Linking (CXL) With Riboflavin
and UV-A is Oxygen Dependent.
AB - PURPOSE: In an attempt to reduce treatment time in corneal collagen cross-linking
(CXL) with riboflavin and ultraviolet-A (UV-A), recent protocol modifications
include shorter irradiation times at higher fluence, while maintaining constant
total applied energy (Bunsen-Roscoe law of reciprocity). While such parameter
changes might produce similar biological results within a certain range, the
limits of reciprocity are unknown. Limitations in the corneal oxygen diffusion
capacity and its potential impact on the efficacy of CXL, raise concerns
regarding the efficiency of high-fluence CXL, and also of transepithelial CXL.
METHODS: Porcine corneas were treated with an epithelium-off CXL at a fluence of
9 mW/cm2 under two different atmospheres: one with a regular oxygen content (21%)
and another in a helium-supplemented, low-oxygen environment (<0.1%). Untreated
corneas served as controls (n = 20 each). Five-millimeter corneal stripes were
prepared and biomechanical stiffness was measured using an extensometer. RESULTS:
Corneas cross-linked under normal oxygen levels showed a significant increase in
biomechanical stability (14.36 MPa +/- 2.69 SD), whereas corneas treated
similarly, but in a low-oxygen atmosphere showed a Young's modulus similar to
untreated controls (11.72 MPa +/- 2.77 SD). CONCLUSIONS: The biomechanical effect
of CXL seems to be oxygen dependent. This dependency will be of particular
importance in high-fluence and transepithelial CXL and will most likely require
major protocol modifications to maintain the efficiency of the method.
TRANSLATIONAL RELEVANCE: The oxygen dependency of CXL shown here raises concerns
about the effectiveness of high-fluence and transepithelial CXL. Both methods
were introduced to clinical ophthalmology without thorough validation.
PMID- 24349886
TI - Patient report: autism spectrum disorder treated with camel milk.
AB - This patient report is about my son, who was diagnosed with autism spectrum
disorder (ASD) at 3 years of age, and the effects I observed when he began
drinking camel milk daily. Beginning at age 9, he drank one half cup of raw camel
milk a day and experienced overnight an improvement in his symptoms. His
continued regular consumption of camel milk was associated with sustained symptom
improvements for 6 consecutive years (2007-2013). This patient report is a road
map of my navigations, consultations with experts and autism care providers, and
the apparent effect of camel milk on autism spectrum disorder (ASD).
PMID- 24349885
TI - My experience learning about autism.
AB - I remember the first time I heard the word "autistic." I was 10 years old, and my
mom mentioned that someone had a child who was autistic. I was confused because I
mistook her description as "artistic." In April 2001, our first child, Isaiah,
was born. My wife, Lanier, was concerned that he had autism at about 11 months of
age, but I did not recognize his obvious problems, even though he was not
responding to his name, was obsessed with spinning objects, and did not play with
toys appropriately. He also had no language, did not walk until 18 months, and
had significant gastrointestinal (GI) problems including severe reflux requiring
medication and chronic diarrhea. At 19 months of age, Isaiah was diagnosed with
autistic disorder.
PMID- 24349887
TI - Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in
Polymyxin B Susceptibility of Pseudomonas aeruginosa.
AB - Polymyxins are often considered as a last resort to treat multidrug resistant P.
aeruginosa but polymyxin resistance has been increasingly reported worldwide in
clinical isolates. Polymyxin resistance in P. aeruginosa is known to be
associated with alterations in either PhoQ or PmrB. In this study, mutant strains
of P. aeruginosa carrying amino acid substitution, a single and/or dual
inactivation of PhoQ and PmrB were constructed to further understand the roles of
PhoQ and PmrB in polymyxin susceptibility. Polymyxin B resistance was caused by
both inactivation and/or amino acid substitutions in PhoQ but by only amino acid
substitutions of PmrB. Alterations of both PhoQ and PmrB resulted in higher
levels of polymyxin B resistance than alteration of either PhoQ or PmrB alone.
These results were confirmed by time-killing assays suggesting that high-level
polymyxin resistance in P. aeruginosa is caused by alterations of both PhoQ and
PmrB.
PMID- 24349888
TI - Pancreatic anastomosis leak 15 years after simultaneous pancreas-kidney
transplantation from late-onset allograft cytomegalovirus duodenal ulcers
presenting with gross hematuria.
AB - Cytomegalovirus (CMV) infection is one of the most important causes of morbidity
and mortality in solid organ transplantation. It can present with hematuria, the
most common urological complication in the early post-simultaneous pancreas
kidney (SPK) transplant period. In SPK transplantation, CMV infection usually
occurs 1 month after transplantation. We report an instance of bladder-drained
SPK transplant presenting with recurrent gross hematuria from CMV infected
duodenal graft ulcers 15 years after preserved well-functioning grafts. Serum
quantitative Polymerase Chain Reaction (qPCR) for CMV was negative. Postmortem
duodenal graft staining for CMV was positive, and revealed the cause of the
inciting ulcer. To our knowledge, our patient is the first reported case of very
late onset invasive CMV disease causing duodenal graft ulcers 15 years after
transplantation, as previously reported cases of posttransplant CMV disease
occurred only as late as 18 months. In addition, the absence of correlation
between CMV viremia and CMV-infected duodenal allograft in SPK transplant has not
been reported. Our case demonstrates that CMV viral load is -unreliable to
diagnose invasive CMV disease, and tissue biopsy should be obtained to avoid
missed diagnosis causing high morbidity and mortality.
PMID- 24349889
TI - Factors affecting household adoption of an evacuation plan in American Samoa
after the 2009 earthquake and tsunami.
AB - American Samoa is still recovering from the debilitating consequences of the
September 29, 2009 tsunami. Little is known about current household preparedness
in American Samoa for future earthquakes and tsunamis. Thus, this study sought to
enumerate the number of households with an earthquake and tsunami evacuation plan
and to identify predictors of having a household evacuation plan through a post
tsunami survey conducted in July 2011. Members of 300 households were interviewed
in twelve villages spread across regions of the principle island of Tutuila.
Multiple logistic regression showed that being male, having lived in one's home
for < 30 years, and having a friend who suffered damage to his or her home during
the 2009 tsunami event increased the likelihood of having a household evacuation
plan. The prevalence of tsunami evacuation planning was 35% indicating that
survivors might feel that preparation is not necessary given effective adaptive
responses during the 2009 event. Results suggest that emergency planners and
public health officials should continue with educational outreach to families to
spread awareness around the importance of developing plans for future earthquakes
and tsunamis to help mitigate human and structural loss from such natural
disasters. Additional research is needed to better understand the linkages
between pre-event planning and effective evacuation responses as were observed in
the 2009 events.
PMID- 24349890
TI - Evaluating the impact of a school-based prevention program on self-esteem, body
image, and risky dieting attitudes and behaviors among Kaua'i youth.
AB - Eating disorders and obesity (EDO) are increasing among youth, having serious
long-term physical and psychological consequences. The purpose of this study was
to determine if significant differences exist in EDO risk factors following
participation of 4-6th grade students in a school-based EDO prevention
curriculum. This community-based research project assessed students at baseline
and one week following EDO intervention. Primary outcome variables measured self
esteem, body dissatisfaction, and high risk eating attitudes and behaviors. Pre
and post-test differences were calculated using mixed models, correcting for
clustering within schools and teachers. This study found mean changes in all
scores in healthy directions, as well as movement of students into lower risk
groups post-intervention. This program demonstrated that a classroom curriculum
is associated with decreased risks of EDO in boys and girls, supporting
prevention programs at an early age for both sexes. Studies to determine long
term benefit and guide booster interventions are warranted.
PMID- 24349891
TI - Treatment of median arcuate ligament syndrome via traditional and robotic
techniques.
AB - Median arcuate ligament syndrome (MALS) is a rare entity characterized by
extrinsic compression of the celiac artery and symptoms of postprandial
epigastric pain, nausea, vomiting, and weight loss mimicking mesenteric ischemia.
We present two patients diagnosed with MALS, the first treated with an open
laparotomy by a vascular surgeon and the second using a robot assisted
laparoscopic approach by a general surgeon with a vascular surgeon on standby.
This is the second ever report of this approach. Both patients recovered without
complications and experienced resolution of their symptoms. A discussion of the
pathophysiology, literature review, and multispecialty treatment approach are
presented.
PMID- 24349892
TI - Medical school hotline: Homelessness in Hawai'i: challenges, progress, and
prospects.
PMID- 24349895
TI - Automated analysis of clonal cancer cells by intravital imaging.
AB - Longitudinal analyses of single cell lineages over prolonged periods have been
challenging particularly in processes characterized by high cell turn-over such
as inflammation, proliferation, or cancer. RGB marking has emerged as an elegant
approach for enabling such investigations. However, methods for automated image
analysis continue to be lacking. Here, to address this, we created a number of
different multicolored poly- and monoclonal cancer cell lines for in vitro and in
vivo use. To classify these cells in large scale data sets, we subsequently
developed and tested an automated algorithm based on hue selection. Our results
showed that this method allows accurate analyses at a fraction of the
computational time required by more complex color classification methods.
Moreover, the methodology should be broadly applicable to both in vitro and in
vivo analyses.
PMID- 24349893
TI - Insights in public health: taxing sugar sweetened beverages to improve public
health: policy action in Hawai'i. Doctoral Health Policy Seminar, Spring 2013.
PMID- 24349896
TI - Altering an extended phenotype reduces intraspecific male aggression and can
maintain diversity in cichlid fish.
AB - Reduced male aggression towards different phenotypes generating negative
frequency-dependent intrasexual selection has been suggested as a mechanism to
facilitate the invasion and maintenance of novel phenotypes in a population. To
date, the best empirical evidence for the phenomenon has been provided by
laboratory studies on cichlid fish with different colour polymorphisms. Here we
experimentally tested the hypothesis in a natural population of Lake Malawi
cichlid fish, in which males build sand-castles (bowers) to attract females
during seasonal leks. We predicted that if bower shape plays an important role in
male aggressive interactions, aggression among conspecific males should decrease
when their bower shape is altered. Accordingly, we allocated randomly chosen
bowers in a Nyassachromis cf. microcephalus lek into three treatments: control,
manipulated to a different shape, and simulated manipulation. We then measured
male behaviours and bower shape before and after these treatments. We found that
once bower shape was altered, males were involved in significantly fewer
aggressive interactions with conspecific males than before manipulation. Mating
success was not affected. Our results support the idea that an extended
phenotype, such as bower shape, can be important in maintaining polymorphic
populations. Specifically, reduced male conspecific aggression towards males with
different extended phenotypes (here, bower shapes) may cause negative frequency
dependent selection, allowing the invasion and establishment of a new phenotype
(bower builder). This could help our understanding of mechanisms of
diversification within populations, and in particular, the overall
diversification of bower shapes within Lake Malawi cichlids.
PMID- 24349897
TI - A feasibility open trial of internet-delivered cognitive-behavioural therapy
(iCBT) among consumers of a non-governmental mental health organisation with
anxiety.
AB - Background. To date the efficacy and acceptability of internet-delivered
cognitive behavioural treatments (iCBT) has been examined in clinical trials and
specialist facilities. The present study reports the acceptability, feasibility
and preliminary efficacy of an established iCBT treatment course (the Wellbeing
Course) administered by a not-for-profit non-governmental organisation, the
Mental Health Association (MHA) of New South Wales, to consumers with symptoms of
anxiety. Methods. Ten individuals who contacted the MHA's telephone support line
or visited the MHA's website and reported at least mild symptoms of anxiety (GAD
7 total scores >=5) were admitted to the study. Participants were provided access
to the Wellbeing Course, which comprises five online lessons and homework
assignments, and brief weekly support from an MHA staff member via telephone and
email. The MHA staff member was an experienced mental health professional and
received minimal training in administering the intervention. Results. All 10
participants completed the course within the 8 weeks. Post-treatment and two
month follow-up questionnaires were completed by all participants. Mean within
group effect sizes (Cohen's d) for the Generalized Anxiety Disorder 7 Item (GAD
7) and Patient Health Questionnaire 9 Item (PHQ-9) were large (i.e., > .80) and
consistent with previous controlled research. The Course was also rated as highly
acceptable with all 10 participants reporting it was worth their time and they
would recommend it to a friend. Conclusions. These results provide support for
the potential clinical utility of iCBT interventions and the acceptability and
feasibility of employing non-governmental mental health organisations to deliver
these treatments. However, further research is needed to examine the clinical
efficacy and cost-effectiveness of delivering iCBT via such organisations.
PMID- 24349898
TI - Fine motor deficits in reading disability and language impairment: same or
different?
AB - Several studies have found evidence of motor deficits in poor readers. There is
no obvious reason for motor and literacy skills to go together, and it has been
suggested that both deficits could be indicative of an underlying problem with
cerebellar function and/or procedural learning. However, the picture is
complicated by the fact that reading problems often co-occur with oral language
impairments, which have also been linked with motor deficits. This raises the
question of whether motor deficits characterise poor readers when language
impairment has been accounted for - and vice versa. We considered these questions
by assessing motor deficits associated with reading disability (RD) and language
impairment (LI). A large community sample provided a subset of 9- to 10-year
olds, selected to oversample children with reading and/or language difficulties,
to give 37 children with comorbid LI + RD, 67 children with RD only, 32 children
with LI only, and 117 typically-developing (TD) children with neither type of
difficulty. These children were given four motor tasks that taxed speed,
sequence, and imitation abilities to differing extents. Different patterns of
results were found for the four motor tasks. There was no effect of RD or LI on
two speeded fingertip tapping tasks, one of which involved sequencing of
movements. LI, but not RD, was associated with problems in imitating hand
positions and slowed performance on a speeded peg-moving task that required a
precision grip. Fine motor deficits in poor readers may be more a function of
language impairment than literacy problems.
PMID- 24349899
TI - Diversity and distribution of extra-floral nectaries in the cerrado savanna
vegetation of Brazil.
AB - Aim. Throughout evolutionary history, plants and animals have evolved alongside
one another. This is especially apparent when considering mutualistic
relationships such as between plants with extra-floral nectaries (EFNs, glands on
leaves or stems that secrete nectar) and the ants that visit them. Ants are
attracted by the nectar and then protect the plant against destructive
herbivores. The distribution of these plants is of particular interest, because
it can provide insights into the evolutionary history of this unique trait and
the plants that possess it. In this study, we investigated factors driving the
distribution of woody plants with EFNs in the cerrado vegetation of Brazil.
Location. Brazil Methods. We used a database detailing the incidence of 849 plant
species at 367 cerrado sites throughout Brazil. We determined which species
possessed EFNs and mapped their distributions. We tested for correlations between
the proportion of EFN species at each site and (i) three environmental variables
(mean annual temperature, mean annual precipitation, and the precipitation in the
driest quarter of the year), (ii) a broad soil classification, and (iii) the
total species diversity of each site. Results. We found a wide range in the
proportion of EFN species at any one site (0-57%). However, whilst low diversity
sites had wide variation in the number of EFN species, high diversity sites all
had few EFN species. The proportion of EFN species was positively correlated with
absolute latitude and negatively correlated with longitude. When accounting for
total species diversity, the proportion of EFN species per site was negatively
correlated with precipitation in the driest quarter of the year and positively
correlated with temperature range. Main Conclusions. These results suggest either
that herbivore pressure may be lower in drier sites, or that ants are not as
dominant in these locations, or that plant lineages at these sites were unable to
evolve EFNs.
PMID- 24349900
TI - Differential roles of prostaglandin E-type receptors in activation of hypoxia
inducible factor 1 by prostaglandin E1 in vascular-derived cells under non
hypoxic conditions.
AB - Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, has vasodilatory
properties and is used widely in various clinical settings. In addition to acute
vasodilatory properties, PGE1 may exert beneficial effects by altering protein
expression of vascular cells. PGE1 is reported to be a potent stimulator of
angiogenesis via upregulation of VEGF expression, which is under the control of
the transcription factor hypoxia-inducible factor 1 (HIF-1). However, the
molecular mechanisms behind the phenomenon are largely unknown. In the present
study, we investigated the mechanism by which PGE1 induces HIF-1 activation and
VEGF gene expression in human aortic smooth muscle cells (HASMCs) and human
umbilical vein endothelial cells (HUVECs), both vascular-derived cells. HUVECs
and HASMCs were treated with PGE1 at clinically relevant concentrations under 20%
O2 conditions and HIF-1 protein expression was investigated. Expression of HIF-
1alpha protein and the HIF-1-downstream genes were low under 20% O2 conditions
and increased in response to PGE1 treatment in both HUVECs and HASMCs in a dose-
and time-dependent manner under 20% O2 conditions as comparable to exposure to 1%
O2 conditions. Studies using EP-receptor-specific agonists and antagonists
revealed that EP1 and EP3 are critical to PGE1-induced HIF-1 activation. In vitro
vascular permeability assays using HUVECs indicated that PGE1 increased vascular
permeability in HUVECs. Thus, we demonstrate that PGE1 induces HIF- 1alpha
protein expression and HIF-1 activation under non-hypoxic conditions and also
provide evidence that the activity of multiple signal transduction pathways
downstream of EP1 and EP3 receptors is required for HIF-1 activation.
PMID- 24349901
TI - Biotic, abiotic and management controls on methanol exchange above a temperate
mountain grassland.
AB - Methanol (CH3OH) fluxes were quantified above a managed temperate mountain
grassland in the Stubai Valley (Tyrol, Austria) during the growing seasons 2008
and 2009. Half-hourly methanol fluxes were calculated by means of the virtual
disjunct eddy covariance (vDEC) method using 3-dimensional wind data from a sonic
anemometer and methanol volume mixing ratios measured with a proton-transfer
reaction mass spectrometer (PTR-MS). During (undisturbed) mature and growing
phases methanol fluxes exhibited a clear diurnal cycle with close-to-zero fluxes
during nighttime and emissions, up to 10 nmol m-2 s-1, which followed the diurnal
course of radiation and air temperature. Management events were found to
represent the largest perturbations of methanol exchange at the studied grassland
ecosystem: Peak emissions of 144.5 nmol m-2 s-1 were found during/after cutting
of the meadow reflecting the wounding of the plant material and subsequent
depletion of the leaf internal aqueous methanol pools. After the application of
organic fertilizer, elevated methanol emissions of up to 26.7 nmol m-2 s-1 were
observed, likely reflecting enhanced microbial activity associated with the
applied manure. Simple and multiple linear regression analyses revealed air
temperature and radiation as the dominant abiotic controls, jointly explaining 47
% and 70 % of the variability in half-hourly and daily methanol fluxes. In
contrast to published leaf-level laboratory studies, the surface conductance and
the daily change in the amount of green plant area, used as ecosystem-scale
proxies for stomatal conductance and growth, respectively, were found to exert
only minor biotic controls on methanol exchange.
PMID- 24349902
TI - Influence of secondary structure on in-source decay of protein in matrix-assisted
laser desorption/ionization mass spectrometry.
AB - The susceptibility of the N-Calpha bond of the peptide backbone to specific
cleavage by in-source decay (ISD) in matrix-assisted laser desorption/ionization
mass spectrometry (MALDI MS) was studied from the standpoint of the secondary
structure of three proteins. A naphthalene derivative, 5-amino-1-naphtol (5,1
ANL), was used as the matrix. The resulting c'-ions, which originate from the
cleavage at N-Calpha bonds in flexible secondary structures such as turn and
bend, and are free from intra-molecular hydrogen-bonded alpha-helix structure,
gave relatively intense peaks. Furthermore, ISD spectra of the proteins showed
that the N-Calpha bonds of specific amino acid residues, namely Gly-Xxx, Xxx-Asp,
and Xxx-Asn, were more susceptible to MALDI-ISD than other amino acid residues.
This is in agreement with the observation that Gly, Asp and Asn residues usually
located in turns, rather than alpha-helix. The results obtained indicate that
protein molecules embedded into the matrix crystal in the MALDI experiments
maintain their secondary structures as determined by X-ray crystallography, and
that MALDI-ISD has the capability for providing information concerning the
secondary structure of protein.
PMID- 24349903
TI - Matrix effect on in-source decay products of peptides in matrix-assisted laser
desorption/ionization.
AB - MALDI-ISD of peptides were studied using several salicylic acid derivatives, 2,5
dihydroxybenzoic acid (2,5-DHB), 5-aminosalicylic acid (5-ASA), 5-formylsalicylic
acid (5-FSA), and 5-nitrosalicylic acid (5-NSA) as matrices. The difference in
the nature of the functional group at the 5-position in the salicylic acid
derivatives can dramatically affect the ISD products. The use of 2,5-DHB and 5
ASA leads to "hydrogen-abundant" peptide radicals and subsequent radical-induced
N-Calpha bonds cleavage. N-Calpha bond cleavage gave a c'/z (.) fragment pair and
radical z (.)-series fragments gain a hydrogen radical or react with a matrix
radical. In contrast, the use of 5-NSA resulted in the production of a "hydrogen
deficient" peptide radical that contained a radical site on the amide nitrogen in
the peptide backbone. Subsequently, the radical site on the amide nitrogen
induces Calpha-C bond dissociation, leading to a (.)/x fragment pair. The a (.)
series ions undergo further hydrogen abstraction to form a-series ions after
Calpha-C bond cleavage. Since the Pro residue does not contain a nitrogen
centered radical site, Calpha-C bond cleavage does not occur. Alternatively, the
specific cleavage of CO-N bonds leads to a b (.)/y fragment pair at Xxx-Pro which
occurs via hydrogen abstraction from the Calpha-H in the Pro residue. The use of
5-FSA generated both a (.)/x- and c'/z (.)-series fragment pairs. An oxidizing
matrix provides useful complementary information in MALDI-ISD compared to a
reducing matrix for the analysis of amino acid sequencing and site localization
in cases of phosphopeptides. MALDI-ISD, when used in conjunction with both
reducing and oxidizing matrices is a potentially useful method for de novo
peptide sequencing.
PMID- 24349904
TI - In Situ Pressure Probe Sampling and UV-MALDI MS for Profiling Metabolites in
Living Single Cells.
AB - In this work we describe the use of a combination of a cell pressure probe and a
UV-matrix-assisted laser desorption/ionization time of flight (UV-MALDI-TOF) mass
spectrometer for the in situ picoliter sampling and shotgun metabolite profiling
of living single cells of plants. In addition to quantifiable sampling, the
pressure probe has some unique features which differentiate it from other single
cell analytical tools. Cell wall and plasma membrane properties and water
relations of in situ living single cells can be analyzed before sampling the cell
sap. In addition, the fully-controlled sampling of cells located at different
depths in plant tissues, measurement of the sample volume, and the addition of
internal standards are facilitated by the pressure probe. Using a variety of
organic compounds and nanoparticles as UV-MALDI matrices, metabolites from
neutral carbohydrates to amino acids and other metabolites can be detected
through UV-MALDI-TOF mass spectrometry analyses of picoliter-sized, single-cell
samples.
PMID- 24349906
TI - Hydrogen radical removal causes complex overlapping isotope patterns of aromatic
carboxylic acids in negative-ion matrix-assisted laser desorption/ionization mass
spectrometry.
AB - We studied the ionization process of aromatic carboxylic acids, including ones
with or without hydroxy groups in matrix-assisted laser desorption/ionization
mass spectrometry (MALDI-MS), because many natural products, metabolites, and
drags contain those structural units. In the actual experimental data, benzoic
acid was ionized as only deprotonated molecule [M-H](-). In contrast, both of
negative molecular ion M(-) and deprotonated molecule [M-H](-) were generated
from 2-naphthoic acid and 2-anthracenecarboxylic acid, and the ratio of negative
molecular ion to deprotonated molecule M(-)/[M-H](-) was increased in 2
anthracenecarboxylic acid. In addition, the ratio of 2-anthracenecarboxylic acid
was much higher than those of 1- and 9-anthracenecarboxylic acids among the three
isomers. Therefore, 2-substitution induced the generation of the negative
molecular ion M(-), which can made us prediction of the substituted positions
from their overlapping peak isotope patterns. 2,5-Dihydroxybenzoic acid (2,5
DHBA) showed two deprotonated molecules, [M-H](-) and [M-H*-H](-), which was
generated from a neutral hydrogen radical (H*) removal from a phenolic hydroxy
group. The deprotonated molecule [M-H*-H](-) of 2,5-DHBA was the most abundant
among six DHBAs and three hydroxybenzoic acids (hBAs). This observation raises
the possibility that such a property of 2,5-DHBA could be a clue to explain its
highest efficiency as a MALDI matrix. The order of the hydrogen radical removal
from the phenolic hydroxy groups was the 3-<4-?5-positions in the DHBAs, and the
3-<4-positions in hBAs. We can distinguish among six DHBA isomers and three hBA
isomers from their spectral pattern around the deprotonated molecules [M-H*-H](-)
and [M-H](-). The intra-molecular hydrogen bonding between 1-carboxy and 2
hydroxy groups was an important factor in hydrogen radical removal in the
hydroxylbenzoic acids and dihydroxybenzoic acids.
PMID- 24349905
TI - Matrix-Assisted Laser Desorption/Ionization (MALDI) Imaging Mass Spectrometry
(IMS): A Challenge for Reliable Quantitative Analyses.
AB - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry
(IMS) is capable of determining the distribution of hundreds of molecules at once
directly from tissue sections. Since tissues are analyzed intact without
homogenization, spatial relationships of molecules are preserved. The technology
is, therefore, undoubtedly powerful to investigate the molecular complexity of
biological processes. However, several technical refinements are essential for
full exploitation of MALDI-IMS to dictate dynamics alteration of biomolecules in
situ; these include ways to collect tissues, target-specific tissue pretreatment,
matrix choice for efficient ionization, and matrix deposition method to improve
imaging resolution. Furthermore, for MALDI-IMS to reach its full potential,
quantitative property in the IMS should be strengthened. We review the challenges
and new approaches for optimal imaging of proteins, lipids and metabolites,
highlighting a novel quantitative IMS of energy metabolites in the recent
literature.
PMID- 24349907
TI - Correlation between Sweet Spots of Glycopeptides and Polymorphism of the Matrix
Crystal in MALDI Samples.
AB - A standard dried-droplet preparation using 2,5-dihydroxybenzoic acid (2,5-DHBA)
as the matrix results in a large variation in signal intensity and poor shot-to
shot reproducibility in matrix-assisted laser desorption/ionization (MALDI). We
expected that the differences can be attributed to the nature of the crystal
structures in the region of the "sweet spot" within the MALDI samples. 2,5-DHBA
crystals with and without analytes on a target plate obtained by means of a dried
droplet preparation contain two polymorphs, which can be distinguished by Raman
spectra. In comparing the Raman image with the MS image, a clear correlation
between the signal distribution of glycopeptides and hydrophilic peptides and the
specific crystal form of 2,5-DHBA could be made. The ionization of hydrophobic
peptides appears to proceed in both types of polymorphic crystals. In addition,
the derivatization of glycopeptides with a pyrene group enabled us to detect
glycopeptides regardless the crystal form. As the result, the number of sweet
spots increased and MS spectra with a high signal intensity were obtained. The
results suggest that the introduction of a hydrophobic/aromatic moiety to
glycopeptides results in a more successful MALDI analysis due to the effective
incorporation of the analyte into matrix crystals.
PMID- 24349908
TI - Flexible xxx-asp/asn and gly-xxx residues of equine cytochrome C in matrix
assisted laser desorption/ionization in-source decay mass spectrometry.
AB - The backbone flexibility of a protein has been studied from the standpoint of the
susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted
laser desorption/ionization mass spectrometry (MALDI MS). Residues more
susceptible to MALDI-ISD, namely Xxx-Asp/Asn and Gly-Xxx, were identified from
the discontinuous intense peak of c'-ions originating from specific cleavage at N
Calpha bonds of the backbone of equine cytochrome c. The identity of the residues
susceptible to ISD was consistent with the known flexible backbone amides as
estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these
flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that
these residues are preferred in flexible secondary structure free from
intramolecular hydrogen-bonded structures such as alpha-helix and beta-sheet. The
MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side
c'-ions originating from N-Calpha bond cleavage at Xxx-Asp/Asn and Gly-Xxx
residues, but also C-terminal side complement z'-ions originating from the same
cleavage sites. The present study implies that MALDI-ISD can give information
about backbone flexibility of proteins, comparable with the protection factors
estimated by HDX.
PMID- 24349909
TI - Label-free analysis of o-glycosylation site-occupancy based on the signal
intensity of glycopeptide/peptide ions.
AB - Mucin-type O-glycosylation is a major posttranslational modification of proteins.
The level of O-glycosylation at a site could be useful in terms of evaluating
various disease conditions. To address the feasibility of measuring O
glycosylation levels based on the glycopeptide ion intensity in a mass spectrum,
apolipoprotein CIII (apoC3), a protein that contains a single core-1 O-glycan Gal
GalNAc disaccharide was analyzed by matrix-assisted laser desorption ionization
(MALDI) time-of-flight (TOF) mass spectrometry (MS). The intensity of protonated
ions for an equimolar mixture of desialylated and deglycosylated apoC3s were the
same in linear TOF measurements. No substantial in-source decay, including the
cleavage of the protein-sugar linkage was observed. The glycopeptide derived from
apoC3 and the unglycosylated counterpart, when analyzed by MALDI reflectron TOF
MS indicated that post-source decay was minimal. These collective findings
demonstrate the feasibility of label-free quantitation of O-glycan occupancy by
MS when the glycans are small and neutral. This method provides a tool for use in
glycoproteomics as a complement of our previous report (DOI: 10.1021/pr900913k)
for calculating the saccharide composition of O-glycans.
PMID- 24349910
TI - Construction of a newly designed small-size mass spectrometer for helium isotope
analysis: toward the continuous monitoring of (3)he/(4)he ratios in natural
fluids.
AB - The construction of a small-size, magnetic sector, single focusing mass
spectrometer (He-MS) for the continuous, on-site monitoring of He isotope ratios
((3)He/(4)He) is described. The instrument is capable of measuring (4)He/(20)Ne
ratios dissolved in several different types of natural fluids of geochemical
interest, such as groundwater and gas from hot springs, volcanoes and gas well
fields. The ion optics of He-MS was designed using an ion trajectory simulation
program "TRIO," which permits the simultaneous measurement of (3)He and (4)He
with a double collector system under a mass resolution power (M/DeltaM) of >700.
The presently attained specifications of He-MS are; (1) a mass resolving power of
ca. 430, sufficient to separate (3)He(+) from interfering ions, HD(+) and H3 (+),
(2) ultra-high vacuum conditions down to 3*10(-8) Pa, and (3) a sufficiently high
sensitivity to permit amounts of (3)He to be detected at levels as small as 10(
13) cm(3) STP (3*10(6) atoms). Long term stability for (3)He/(4)He analysis was
examined by measuring the (3)He/(4)He standard gas (HESJ) and atmospheric He,
resulting in ~3% reproducibility and <=5% experimental error for various amounts
of atmospheric He from 0.3 to 2.3*10(-6) cm(3) STP introduced into the
instrument. A dynamic range of measurable (3)He/(4)He ratios with He-MS is
greater than 10(3) which was determined by measuring various types of natural
fluid samples from continental gas (with a low (3)He/(4)He ratio down to 2*10(
8)) to volcanic gas (with a high (3)He/(4)He ratio up to 3*10(-5)). The accuracy
and precision of (3)He/(4)He and (4)He/(20)Ne ratios were evaluated by comparing
the values with those measured using well established noble gas mass
spectrometers (modified VG5400/MS-III and -IV) in our laboratory, and were found
to be in good agreement within analytical errors. Usefulness of the selective
extraction of He from water/gas using a high permeability of He through a silica
glass wall at high temperature (700 degrees C) is demonstrated.
PMID- 24349911
TI - N (alpha) Selective Acetylation of Peptides.
AB - A chemical tag at the peptide N-terminus, in combination with MS, can be useful
for quantitative analysis, N-terminal peptide identification, or peptide
sequencing. Here we report on the N (alpha) selective acetylation of a peptide
using acetic anhydride, a popular reagent for the modification of amino groups,
without the need for the blocking of lysine side-chain epsilon-amino groups,
which is usually required for N (alpha) selective acetylation. By controlling the
amount of acetic anhydride used and running the reaction at 0 degrees C, it is
possible to preferentially acetylate the alpha-amino group. As a typical
application of the method, a tryptic digest of an N-terminally blocked protein,
cytochrome c, was directly acetylated using the present method. When deuterated
acetic anhydride was used as the reagent, the N-terminal blocked peptide could be
easily identified as a non-labeled ion peak while the N (alpha)-acetyl groups of
all the other peptides were deuterated.
PMID- 24349912
TI - In-Situ U-Pb Dating of Apatite by Hiroshima-SHRIMP: Contributions to Earth and
Planetary Science.
AB - The Sensitive High Resolution Ion MicroProbe (SHRIMP) is the first ion microprobe
dedicated to geological isotopic analyses, especially in-situ analyses related to
the geochronology of zircon. Such a sophisticated ion probe, which can attain a
high sensitivity at a high mass resolution, based on a double focusing high mass
resolution spectrometer, designed by Matsuda (1974), was constructed at the
Australian National University. In 1996, such an instrument was installed at
Hiroshima University and was the first SHRIMP to be installed in Japan. Since its
installation, our focus has been on the in-situ U-Pb dating of the mineral
apatite, as well as zircon, which is a more common U-bearing mineral. This
provides the possibility for extending the use of in-situ U-Pb dating from
determining the age of formation of volcanic, granitic, sedimentary and
metamorphic minerals to the direct determination of the diagenetic age of fossils
and/or the crystallization age of various meteorites, which can provide new
insights into the thermal history on the Earth and/or the Solar System. In this
paper, we review the methodology associated with in-situ apatite dating and our
contribution to Earth and Planetary Science over the past 16 years.
PMID- 24349913
TI - Correlations between Chemical Compositions and Retention Times of Methacrylate
Random Copolymers Using LC-ESI-MS.
AB - Correlations between chemical compositions and chromatographic retention times
(Rt) of methacrylate random copolymers were studied by liquid chromatography
electrospray ionization mass spectrometry (LC-ESI-MS). Twenty-six different
polymers including homopolymers of poly(methyl methacrylate) (PMMA), poly(tert
butyl methacrylate) (PTBMA) and poly(2-hydroxyethyl methacrylate) (PHEMA), and
their random copolymers of P(MMA-TBMA) and P(MMA-HEMA) with known chemical
compositions were studied. The results indicate that there is close correlations
between the chemical compositions of the random copolymers and their Rt of the C8
column in the mass spectral ranges of m/z 1,800-2,000. The LC-ESI-MS analysis
showed molecular weights of the copolymers distribute in the mass range of ca.
500-20,000, and the structures of polymer terminals and their monomer units can
be identified.
PMID- 24349914
TI - Mass Spectrometry Imaging and Structural Analysis of Lipids Directly on Tissue
Specimens by Using a Spiral Orbit Type Tandem Time-of-Flight Mass Spectrometer,
SpiralTOF-TOF.
AB - In this paper, we report the use of mass spectrometry imaging and structural
analysis of lipids directly on a tissue specimen, carried out by means of matrix
assisted laser desorption/ionization tandem time-of-flight mass spectrometry,
using a combination of spiral orbit-type and reflectron-type time-of-flight mass
spectrometers. The most intense peak observed in the mass spectrum from a brain
tissue specimen was confirmed as phosphatidylcholine (34 : 1) [M+K](+), using
tandem mass spectrometry. The charge remote fragmentation channels, which are
characteristically observed using high-energy collision-induced dissociation,
contributed significantly to this confirmation. Accurate mass analysis was
further facilitated by mass correction using the confirmed peak. In mass
spectrometry imaging, the high resolving power of our system could separate
doublet peak of less than 0.1 u difference, which would otherwise be problematic
when using a low-resolution reflectron type time-of-flight mass spectrometer. Two
compounds, observed at m/z 848.56 and 848.65, were found to be located in
complementary positions on a brain tissue specimen. These results demonstrate the
importance of a high-performance tandem time-of-flight mass spectrometer for mass
spectrometry imaging and analysis of observed compounds, to allow distinction
between biological molecules.
PMID- 24349915
TI - Application of High-Resolution MALDI-TOFMS with a Spiral Ion Trajectory for the
Structural Characterization of Free Radical Polymerized Methacrylate Ester
Copolymers.
AB - The structural characterization of copolymers by matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) remains a
challenging task, since their random comonomer distribution creates very
complicated mass spectra. In this study, a high-resolution TOF mass spectrometer
with a spiral ion trajectory was applied to the structural and compositional
characterization of free radical copolymerized poly(methyl methacrylate-co-tert
butyl methacrylate), poly(MMA-co-tBMA)s in ethyl lactate acting as a chain
transfer agent. Virtually complete peak assignments of the isobaric components
within the poly(MMA-co-tBMA)s served to identify the end-group combinations and
copolymer compositions of individual copolymer components, allowing the
distributions of comonomer compositions and six types of end-group combinations
to be evaluated.
PMID- 24349916
TI - Cluster composition distributions of pure ethanol: influence of water and ion
molecule reactions revealed by liquid-ionization tandem mass spectrometry.
AB - Studies of clusters in condensed phase at atmospheric pressure are very important
for understanding the properties and structures of liquids. Liquid-ionization
(LPI) mass spectrometry is useful to study hydrogen-bonded clusters at the liquid
surface and in a gas phase. An improved ion source connected to a tandem mass
spectrometer provides detailed information about clusters. Mass spectra of pure
ethanol (99.5%) observed by the first mass analyzer (Q1) showed neat ethanol
cluster ions (C2H5OH) m H(+) with m up to 10 and hydrate ions (C2H5OH) m (H2O) n
H(+) with m larger than 7 and n=1, such as those with m-n=8-1 and 9-1. When the
flow rate of ethanol (liquid) was increased, large ethanol cluster ions with m
larger than 25 were observed by the second mass analyzer (Q3). It is interesting
to note that neat ethanol cluster ions are more abundant than corresponding (with
the same m) hydrate ions (n=1), and major hydrate ions contain only one molecule
of water. Results indicate that ion-molecule reactions occur between Q1 and Q3,
because such mass spectra have never been observed by Q1. Various results
indicate that neat ethanol clusters exist at the liquid surface and are ionized
to give cluster ions.
PMID- 24349917
TI - The pH Dependence of Product Ion Spectra Obtained from Precursor Ions with the
Same Charge Number in ESI of Carbonic Anhydrase 2.
AB - The effect of solvent conditions, including pH, on product ion spectra obtained
from precursor ions produced by electrospray ionization (ESI) was examined.
Bovine carbonic anhydrase 2 was used as a model protein and the product ions
generated by collision induced dissociation of the whole protein were measured
under several different solvent conditions (pH 5.0, 3.7, and 0.1% HCOOH (pH
2.6)/MeCN (1/1)). The product ion spectra from precursor ions with the same
charge number, the observed m/z values and the relative intensities of the
product ions were similar. It therefore appears that the solvent conditions used
have no effect on the product ion that is generated. On the other hand, different
profiles of the product ion were obtained from precursor ions having different
charge numbers. This indicates that the charge number of the precursor ion
appears to be a major determinant of the product ion species and its relative
intensity in product ion spectra of proteins.
PMID- 24349918
TI - Editorial.
PMID- 24349919
TI - Foreword.
PMID- 24349920
TI - Through a glass darkly: glimpses into the future of mass spectrometry.
AB - The paper has three parts, (i) a brief overview of the main achievements made
using mass spectrometry across all the fields of science, (ii) a survey of some
of the topics currently being pursued most activity, including both applications
and fundamental studies, and (iii) some hints as to what the future of mass
spectrometry might hold with particular emphasis on revolutionary changes in the
subject. Emphasis is given to ambient methods of ionization and their use in
disease diagnosis and to their use in combination with miniature mass
spectrometers for in-situ measurements. Special attention goes to the chemical
aspects of mass spectrometry, including its emerging role as a preparative method
based on accelerated bimolecular reaction rates in solution and on ion soft
landing as a means of surface tailoring. In summary, the paper covers the proud
history, vibrant present and expansive future of mass spectrometry.
PMID- 24349921
TI - Selected examples of gas-phase ion chemistry studies.
AB - Gas-phase ion chemistry is an area in mass spectrometry that has received much
research interest since the mid fifties of the last century. Although the focus
of mass spectrometric research has shifted the last twenty years largely to life
science studies, including proteomics, genomics and metabolomics, there are still
several groups in the world active in gas-phase ion chemistry of both positive
and negative ions, either unimolecularly and/or bimolecularly. In this tutorial
lecture the formation and determination of tautomeric ion structures and intra
ionic catalyzed tautomerization in the gas phase will be discussed. In addition,
an example of formation of different tautomeric structures in protic and aprotic
solvents under electrospray ionization conditions will be given, as established
by gas-phase infrared multiphoton dissociation spectroscopy. This will be
followed by presenting an example of time-resolved MS/MS which enables to
identify the structure of an ion, generated at a particular molecular ion
lifetime. At the end of the lecture the power of ion mobility will be shown in
elucidating the mechanism of epimerization of bis-Troger bases having chiral
nitrogen centers.
PMID- 24349922
TI - Renaissance of cation-radicals in mass spectrometry.
AB - This brief overview addresses the topic that was presented in the Thomson Medal
Award session at the 19th International Mass Spectrometry Conference in Kyoto,
Japan. Mass spectrometry of cation-radicals has enjoyed a remarkable renaissance
thanks to the development of new methods for electron attachment to multiply
charged peptide ions. The charge-reduced ions that are odd-electron species
exhibit interesting reactivity that is useful for peptide and protein sequencing.
The paper briefly reviews the fundamental aspects of the formation, energetics,
and backbone dissociations of peptide cation-radicals.
PMID- 24349923
TI - Peptide radical cations: gender determines dissociation chemistry.
AB - Peptide radicals play a significant role in biology as well as mass spectrometry.
They can be differentiated into two groups: conventional hydrogen-deficient
radicals, e.g. M(+*) as in electron ionization, and much more rare hydrogen
abundant radicals, e.g. [M+2H](+*), as in electron capture/transfer dissociation.
The dissociation chemistries of these two types of radicals are vastly different.
Both types tend to lose small molecules or radical groups, but the overlap
between the losses from different radical types is minimal. The backbone cleavage
for hydrogen-deficient radicals is dominated by Calpha-C cleavage (a (*), x
fragments) and for hydrogen-abundant radicals-by N-Calpha cleavage (c, z (*)
ions). The latter types of fragmentation produces more sequencing information
than the former. Therefore, hydrogen-abundant peptide radicals are more valuable
in mass spectrometry. The efficiency of the main method of their production,
electron capture/transfer dissociation, is however limited by charge reduction.
Alternative methods of generation of hydrogen-abundant radicals are needed to
improve the sequencing capabilities of mass spectrometry.
PMID- 24349924
TI - Thermochemistry of non-covalent ion-molecule interactions.
AB - The thermochemistry of non-covalent ion-molecule complexes has been examined by
measuring quantitative bond dissociation energies using threshold collision
induced dissociation in guided ion beam tandem mass spectrometers (GIBMS). The
methods used are briefly reviewed and several examples of the types of
information and insight that can be obtained from such thermodynamic information
are discussed. The hydration of metal cations, both singly and doubly charged, is
reviewed and the trends elucidated, mainly on the basis of electrostatic
contributions. The binding of alkali metal cations to amino acids has been
examined for a range of systems, with both the overall polarizability of the
amino acid and the local dipole moment of heteroatomic side-chains shown to be
important contributors. The gas-phase interactions of the 12-crown-4 (12C4)
polyether with alkali metal cations, classic molecular recognition systems in
solution, have been newly compared to previous GIBMS work. These results validate
the previous hypothesis that excited conformers were present for Rb(+)(12C4) and
Cs(+)(12C4) and offer clues as to how and why they are formed.
PMID- 24349925
TI - MALDI and Related Methods: A Solved Problem or Still a Mystery?
AB - MALDI ionization mechanisms remain a topic of controversy. Some of the major
modern models are compared, with emphasis on those of the author. Primary
formation, secondary reaction, and loss mechanisms are considered.
PMID- 24349926
TI - What Is the Opposite of Pandora's Box? Direct Analysis, Ambient Ionization, and a
New Generation of Atmospheric Pressure Ion Sources.
AB - The introduction of DART and DESI sources approximately seven years ago led to
the development of a new series of atmospheric pressure ion sources referred to
as "ambient ionization" sources. These fall into two major categories: spray
techniques like DESI or plasma techniques like DART. The selectivity of "direct
ionization," meaning analysis without chromatography and with little or no sample
preparation, depends on the mass spectrometer selectivity. Although high
resolution and tandem mass spectrometry are valuable tools, rapid and simple
sample preparation methods can improve the utility of ambient ionization methods.
The concept of ambient ionization has led to the realization that there are many
more ways to form ions than might be expected. An interesting example is the use
of a flint-and-steel spark source to generate ions from compounds such as
phenolphthalein and Gramicidin S.
PMID- 24349927
TI - Trace level detection of explosives in solution using leidenfrost phenomenon
assisted thermal desorption ambient mass spectrometry.
AB - The present paper demonstrates the detection of explosives in solution using
thermal desorption technique at a temperature higher than Leidenfrost temperature
of the solvent in combination with low temperature plasma (LTP) ionization.
Leidenfrost temperature of a solvent is the temperature above which the solvent
droplet starts levitation instead of splashing when placed on a hot metallic
surface. During this desorption process, slow and gentle solvent evaporation
takes place, which leads to the pre-concentration of less-volatile explosive
molecules in the droplet and the explosive molecules are released at the last
moment of droplet evaporation. The limits of detection for explosives studied by
using this thermal desorption LTP ionization method varied in a range of 1 to 10
parts per billion (ppb) using a droplet volume of 20 MUL (absolute sample amount
90-630 fmol). As LTP ionization method was applied and ion-molecule reactions
took place in ambient atmosphere, various ion-molecule adduct species like
[M+NO2](-), [M+NO3](-), [M+HCO3](-), [M+HCO4](-) were generated together with [M
H](-) peak. Each peak was unambiguously identified using 'Exactive Orbitrap' mass
spectrometer in negative ionization mode within 3 ppm deviation compared to its
exact mass. This newly developed technique was successfully applied to detect
four explosives contained in the pond water and soil sample with minor sample pre
treatment and the explosives were detected with ppb levels. The present method is
simple, rapid and can detect trace levels of explosives with high specificity
from solutions.
PMID- 24349928
TI - Mass resolution and mass accuracy: how much is enough?
AB - Accurate mass measurement requires the highest possible mass resolution, to
ensure that only a single elemental composition contributes to the mass spectral
peak in question. Although mass resolution is conventionally defined as the
closest distinguishable separation between two peaks of equal height and width,
the required mass resolving power can be ~10* higher for equal width peaks whose
peak height ratio is 100 : 1. Ergo, minimum resolving power requires
specification of maximum dynamic range, and is thus 10-100* higher than the
conventional definition. Mass resolving power also depends on mass-to-charge
ratio. Mass accuracy depends on mass spectral signal-to-noise ratio and digital
resolution. Finally, the reliability of elemental composition assignment can be
improved by resolution of isotopic fine structure. Thus, the answer to the
question of "how much is enough mass resolving power" requires that one first
specify S/N ratio, dynamic range, digital resolution, mass-to-charge ratio, and
(if available) isotopic fine structure. The highest available broadband mass
resolving power and mass accuracy is from Fourier transform ion cyclotron
resonance mass spectrometry. Over the past five years, FT-ICR MS mass accuracy
has improved by about an order of magnitude, based on higher magnetic field
strength, conditional averaging of time-domain transients, better mass
calibration (spectral segmentation; inclusion of a space charge term); radially
dispersed excitation; phase correction to yield absorption-mode display; and new
ICR cell segmentation designs.
PMID- 24349929
TI - From Supercomputer Modeling to Highest Mass Resolution in FT-ICR.
AB - Understanding of behavior of ion ensembles inside FT-ICR cell based on the
computer simulation of ion motion gives rise to the new ideas of cell designs.
The recently introduced novel FT-ICR cell based on a Penning ion trap with
specially shaped excitation and detection electrodes prevents distortion of ion
cyclotron motion phases (normally caused by non-ideal electric trapping fields)
by averaging the trapping DC electric field during the ion motion in the ICR
cell. Detection times of 5 min resulting in resolving power close to 40,000,000
have been reached for reserpine at m/z 609 at a magnetic field of only 7 Tesla.
Fine structures of resolved 13Cn isotopic cluster groups could be measured for
molecular masses up to 5.7 kDa (insulin) with resolving power of 4,000,000 at 7
Tesla. Based on resolved fine structure patterns atomic compositions can be
directly determined using a new developed algorithm for fine structure
processing. Mass spectra of proteins and multimers of proteins reaching masses up
to 186 kDa (enolase tetramer) could be measured with isotopic resolution. For
instance, at 7 Tesla resolving power of 800,000 was achieved for enolase dimer
(96 kDa) and 500,000 for molecular masses above 100 kDa. Experimental data
indicate that there is practically no limit for the resolving power of this ICR
cell except by collisional damping in the ultrahigh vacuum chamber.
PMID- 24349930
TI - Pushing the Frontier of High-Definition Ion Mobility Spectrometry Using FAIMS.
AB - Differential ion mobility spectrometry (FAIMS) separates ions in gases based on
the difference between their mobilities in strong and weak electric fields,
captured directly employing a periodic waveform with dissimilar profiles in
opposite polarities. As that difference is not tightly correlated with the ion
size or mass, FAIMS separations are generally quite orthogonal to both
conventional IMS (based on the absolute ion mobility that reflects the physical
ion size) and mass spectrometry (based on mass). Until a few years ago, that
advantage was largely offset by poor FAIMS resolving power (~10-20), an order of
magnitude below that achieved with conventional (drift-tube) IMS. This article
summarizes the major recent technical developments that have raised FAIMS
resolving power up to ~500. These include use of higher and more stable voltages
provided by new waveform generators, novel buffer gas compositions comprising
high helium or hydrogen fractions, and extended filtering times up to ~1 s. These
advances have enabled previously unthinkable analyses such as broad baseline
separations of peptide sequence inversions, localization variants (post
translationally modified peptides with differing PTM attachment sites) even for
the larger "middle-down" peptides and smallest PTMs, and lipid regioisomers.
PMID- 24349931
TI - Cold-spray ionization mass spectrometry: applications in structural coordination
chemistry.
AB - Electrospray ionization (ESI)-mass spectrometry (MS) is generally used for the
characterization of labile supramolecules in which non-covalent bonding
interactions are predominant. However, molecular ions are not detected in many
cases because of their instability, and even if such ions are detected, thermal
decomposition generates fragment ions that also appear in the mass spectrum. Cold
spray ionization (CSI) is designed for the MS detection of labile organic
species. It is used to analyze the structures of biomolecular complexes and
labile organic species in solution. The method, a variant of ESI-MS, operates at
low temperature, allowing simple and precise characterization of labile non
covalent complexes that are difficult or impossible to observe by conventional MS
techniques. The CSI method is particularly suitable for elucidating the
structures of labile organometallic compounds in solution as it offers a means to
investigate the dynamic behavior of unstable molecules and/or labile clusters in
solution. Various labile organic compounds are analyzed by using the CSI method
in the field of organic chemistry. CSI-MS is also used to investigate the
behavior of aggregated steroid compounds, namely, bisguanidinobenzene-benzoic
acid complexes, in solution. This method is a powerful tool for analyzing the
equilibria of multiply linked self-assembling catenanes in solution. Its
application to unstable and complex supramolecules will be shown. We have
developed an effective ionization method that uses metal-complex-based ionization
probes containing 2,6-bis(oxazolinyl) pyridine (pybox) ligands. Using this
method, we were able to detect multiply charged ions of target molecules. This
method was proven to effectively ionize large complex molecules, including
biomolecules and various supramolecules, as well as carbon clusters, such as
fullerenes. Moreover, isotope-labeled pybox-La complexes were used to clearly
detect isotopic labeling shifts. Their applications to multiply charged
ionization, including isotope labeling of biomolecules and carbon clusters using
CSI-MS, will be shown.
PMID- 24349932
TI - Integrating Native Mass Spectrometry and Top-Down MS for Defining Protein
Interactions Important in Biology and Medicine.
AB - Native protein mass spectrometry (MS), the measurement of proteins and protein
complexes from non-denaturing solutions, with electrospray ionization (ESI) has
utility in the biological sciences. Protein complexes exceeding 1 MDa have been
measured by MS and ion mobility spectrometry (IMS), and the data yields
information not only regarding size, but structural details can be revealed also.
ESI-IMS allows the relative stability of protein-ligand binding to be measured.
Top-down MS, the direct dissociation of the intact gas phase biomolecule, can
generate sequence and identity information for monomeric (denatured) proteins,
and topology information for noncovalent protein complexes. For protein complexes
with small molecule ligands, i.e., drugs, cofactors, metals, etc., top-down MS
with electron capture dissociation can be used to elucidate the site(s) of ligand
binding. Increasing protein ESI charging, e.g., supercharging, enhances the
efficiency for dissociation of protein complexes.
PMID- 24349933
TI - Image and Spectral Processing for ToF-SIMS Analysis of Biological Materials.
AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) instruments can rapidly
produce large complex data sets. Within each spectrum, there can be hundreds of
peaks. A typical 256*256 pixel image contains 65,536 spectra. If this is extended
to a 3D image, the number of spectra in a given data set can reach the millions.
The challenge becomes how to process these large data sets while taking into
account the changes and differences between all the peaks in the spectra. This is
particularly challenging for biological materials that all contain the same types
of proteins and lipids, just in varying concentrations and spatial distributions.
This data analysis challenge is further complicated by the limitations in the ion
yield of higher mass, more chemically specific species, and potentially by the
processing power of typical computers. Herein we briefly discuss analysis
methodologies including univariate analysis, multivariate analysis (MVA) methods,
and some of the limitations of ToF-SIMS analysis of biological materials.
PMID- 24349934
TI - Functional group selective derivatization and gas-phase fragmentation reactions
of plasmalogen glycerophospholipids.
AB - A reaction strategy involving functional group selective modification of the O
alkenyl-ether double bond within plasmenyl ether containing lipids using iodine
and methanol, in conjunction with functional group selective derivatization of
amine-containing lipids using a novel (13)C1-S,S'
dimethylthiobutanoylhydroxysuccinimide ester ((13)C1-DMBNHS) reagent, is shown to
improve the capabilities of 'shotgun' high resolution/accurate mass spectrometry
for comprehensive lipidome analysis. Importantly, the characteristic mass shifts
introduced as a result of these derivatization reactions enables the resolution
and unambiguous identification of isobaric mass plasmenyl- and plasmanyl-ether
containing lipid species from within crude complex lipid extracts, without need
for chromatographic fractionation or additional lipid extraction steps prior to
analysis. Additionally, the positive ionization mode tandem mass spectrometry
fragmentation behavior of the derivatized plasmenyl ether containing
glycerophosphocholine and glycerophosphoethanolamine lipids are shown to yield
abundant characteristic product ions that directly enable the assignment of their
molecular lipid identities.
PMID- 24349935
TI - Is high throughput glycomics possible?
AB - The role of glycosylation and their biological functions whether as free
oligosaccharides or glycoconjugates has been made possible by the recent
advancements in the analyses of these compounds. The heterogeneity and the large
structural diversity have made oligosaccharide analysis significantly more
difficult than other biopolymers. The next stage of development is to achieve
high throughput analysis. However, the structural elucidation of oligosaccharides
remains an extremely difficult task. Recent reports reveal that the diversity of
structures in a given biological system is finite and may not be large. It may be
possible to create a database of structures that can be used to determine the
identity of known compounds. This capability would therefore make high throughput
glycomics possible. Achieving this task depends on the proper selection of
chemical characteristics to identify the compound. In this presentation, nanoflow
liquid chromatography retention times, accurate mass, and tandem MS is used to
determine structure with a high degree of certainty. The method is used to
determine the biological function of milk oligosaccharides as well as to discover
glycan-based biomarkers for diseases.
PMID- 24349936
TI - Correlation between Serum Levels of Protein-Bound Uremic Toxins in Hemodialysis
Patients Measured by LC/MS/MS.
AB - Uremic toxins are involved in a variety of symptoms in advanced chronic kidney
disease. Especially, the accumulation of protein-bound uremic toxins in the blood
of dialysis patients might play an important role in the development of
cardiovascular disease. Serum concentration of protein-bound uremic toxins such
as indoxyl sulfate, indoxyl glucuronide, indoleacetic acid, p-cresyl sulfate, p
cresyl glucuronide, phenyl sulfate, phenyl glucuronide, phenylacetic acid,
phenylacetylglutamine, hippuric acid, 4-ethylphenyl sulfate, and 3-carboxy-4
methyl-5-propyl-2-furanpropionic acid (CMPF) in hemodialysis patients were
simultaneously measured by liquid chromatography/tandem mass spectrometry. Serum
levels of these protein-bound uremic toxins were increased in hemodialysis
patients. Indoxyl sulfate, p-cresyl sulfate, and CMPF could not be removed
efficiently by hemodialysis due to their high protein-binding ratios. Serum level
of total indoxyl sulfate did not show any significant correlation with total p
cresyl sulfate. However, free indoxyl sulfate correlated with free p-cresyl
sulfate, and reduction rate by hemodialysis of indoxyl sulfate correlated with
that of p-cresyl sulfate. Serum levels of total and free indoxyl sulfate showed
significantly positive correlation with those of indoxyl glucuronide, phenyl
sulfate, and phenyl glucuronide. Serum levels of total and free p-cresyl sulfate
showed significantly positive correlation with those of p-cresyl glucuronide,
phenylacetylglutamine, and phenylacetic acid. Indoxyl sulfate and indoxyl
glucuronide are produced from indole which is produced in the intestine from
tryptophan by intestinal bacteria. p-Cresyl sulfate and p-cresyl glucuronide are
produced from p-cresol which is produced in the intestine from tyrosine by
intestinal bacteria. Thus, intestinal bacteria play an important role in the
metabolism of protein-bound uremic toxins.
PMID- 24349937
TI - Powerful GC-TOF-MS Techniques for Screening, Identification and Quantification of
Halogenated Natural Products.
AB - Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry
(GC*GC TOFMS) and gas chromatography/high-resolution time-of-flight mass
spectrometry (GC-HRT) were used to detect and identify halogenated natural
products (HNPs) in tissue homogenate, in this case brominated analytes present in
a marine snail. Two classes of brominated anthropogenic compounds, polybrominated
diphenyl ethers (PBDEs) and brominated dibenzofurans, were analyzed for
comparison. Following conventional preparation, the sample was analyzed using
GC*GC-TOF-MS. Isotope ratio scripts were used to compile a list of putatively
brominated analytes from amongst the thousands of features resolved in the two
dimensional chromatogram. The structured nature of the chromatogram was exploited
to propose identifications for several classes of brominated compounds, and
include additional candidates that fell marginally outside the script tolerances.
The sample was subsequently analyzed by GC-HRT. The high-resolution mass spectral
data confirmed many formula assignments, facilitated confident assignment of an
alternate formula when an original proposal did not hold, and enabled unknown
identification. Identified HNPs include hydroxylated and methoxylated PBDE
analogs, polybrominated dibenzo-p-dioxins (PBDDs) and hydroxyl-PBDDs, permitting
the environmental occurrence and fate of such compounds to be studied.
PMID- 24349938
TI - Chiral chemicals as tracers of atmospheric sources and fate processes in a world
of changing climate.
AB - Elimination of persistent organic pollutants (POPs) under national and
international regulations reduces "primary" emissions, but "secondary" emissions
continue from residues deposited in soil, water, ice and vegetation during former
years of usage. In a future, secondary source controlled world, POPs will follow
the carbon cycle and biogeochemical processes will determine their transport,
accumulation and fate. Climate change is likely to affect mobilisation of POPs
through e.g., increased temperature, altered precipitation and wind patterns,
flooding, loss of ice cover in polar regions, melting glaciers, and changes in
soil and water microbiology which affect degradation and transformation. Chiral
compounds offer advantages for following transport and fate pathways because of
their ability to distinguish racemic (newly released or protected from microbial
attack) and nonracemic (microbially degraded) sources. This paper discusses the
rationale for this approach and suggests applications where chiral POPs could aid
investigation of climate-mediated exchange and degradation processes. Multiyear
measurements of two chiral POPs, trans-chlordane and alpha-HCH, at a Canadian
Arctic air monitoring station show enantiomer compositions which cycle
seasonally, suggesting varying source contributions which may be under climatic
control. Large-scale shifts in the enantioselective metabolism of chiral POPs in
soil and water might influence the enantiomer composition of atmospheric
residues, and it would be advantageous to include enantiospecific analysis in
POPs monitoring programs.
PMID- 24349939
TI - Advances in isotope ratio mass spectrometry and required isotope reference
materials.
AB - The article gives a condensed version of the keynote lecture held at the
International Mass Spectrometry Conference 2012 in Kyoto. Starting with some
examples for isotope research the key requirements for metrologically valid
procedures enabling traceable and comparable isotope data are discussed. Of
course multi-collector mass spectrometers are required which offer sufficiently
high isotope ratio precision for the intended research work. Following this,
corrections for mass fractionation/discrimination, validation of the analytical
procedure including chemical sample preparation and complete uncertainty budgets
are the most important issues for obtaining a metrologically valid procedure for
isotope ratio determination. Only the application of such metrologically valid
procedures enables the generation of traceable and comparable isotope data. To
realize this suitable isotope and/or delta-reference materials are required,
which currently are not sufficiently available for most isotope systems. Boron is
given as an example, for which the situation regarding isotope and delta
reference materials is excellent. Boron may therefore serve as prototype for
other isotope systems.
PMID- 24349940
TI - Extractive electrospray ionization mass spectrometry for uranium chemistry
studies.
AB - Uranium chemistry is of sustainable interest. Breakthroughs in uranium studies
make serious impacts in many fields including chemistry, physics, energy and
biology, because uranium plays fundamentally important roles in these fields.
Substantial progress in uranium studies normally requires development of novel
analytical tools. Extractive electrospray ionization mass spectrometry (EESI-MS)
is a sensitive technique for trace detection of various analytes in complex
matrices without sample pretreatment. EESI-MS shows excellent performance for
monitoring uranium species in various samples at trace levels since it tolerates
extremely complex matrices. Therefore, EESI-MS is an alternative choice for
studying uranium chemistry, especially when it combines ion trap mass
spectrometry. In this presentation, three examples of EESI-MS for uranium
chemistry studies will be given, illustrating the potential applications of EESI
MS in synthesis chemistry, physical chemistry, and analytical chemistry of
uranium. More specifically, case studies on EESI-MS for synthesis and
characterization of novel uranium species, and for rapid detection of uranium and
its isotope ratios in various samples will be presented. Novel methods based on
EESI-MS for screening uranium ores and radioactive iodine-129 will be presented.
PMID- 24349941
TI - MALDI Imaging Mass Spectrometry-A Mini Review of Methods and Recent Developments.
AB - As the only imaging method available, Imaging Mass Spectrometry (IMS) can
determine both the identity and the distribution of hundreds of molecules on
tissue sections, all in one single run. IMS is becoming an established research
technology, and due to recent technical and methodological improvements the
interest in this technology is increasing steadily and within a wide range of
scientific fields. Of the different IMS methods available, matrix-assisted laser
desorption/ionization (MALDI) IMS is the most commonly employed. The course at
IMSC 2012 in Kyoto covered the fundamental principles and techniques of MALDI
IMS, assuming no previous experience in IMS. This mini review summarizes the
content of the one-day course and describes some of the most recent work
performed within this research field.
PMID- 24349943
TI - Pangola grass as forage for ruminant animals: a review.
AB - This review focuses on the introduction and investigation of pangola grass as a
tropical forage species especially in Thailand. Pangola grass (Digitaria eriantha
Steud., synonym D. decumbens) is one of recent examples of grasses that have been
successfully introduced to Southeast Asia and is often considered as one of the
highest quality tropical grasses popularly grown as pasture. Pangola grass is
utilized extensively as grass for animal grazing, hay and silage making. Its
crude protein content is commonly in the order of 5 to 14% of dry matter and may
exceed 15% of dry matter with young regrowth under high fertilization. It has
been documented that the type and number of ruminants receiving pangola grass can
determine the success of its use. Results obtained when pangola grass in fresh,
hay or silage form was fed to ruminant animals as supplements showed better
performances in body weight gain, feed conversion ratio, carcass yield, meat
quality, and milk yield and composition. In conclusion, pangola grass is a
promising forage and a source of high quality feed for ruminant animals in
tropical countries.
PMID- 24349944
TI - Evaluation of rhizosphere, rhizoplane and phyllosphere bacteria and fungi
isolated from rice in Kenya for plant growth promoters.
AB - Rice (Oryza sativa L.) is the most important staple food crop in many developing
countries, and is ranked third in Kenya after maize and wheat. Continuous
cropping without replenishing soil nutrients is a major problem in Kenya
resulting to declining soil fertility. The use of chemical fertilizers to avert
the problem of low soil fertility is currently limited due to rising costs and
environmental concerns. Many soil micro-organisms are able to solubilize the
unavailable phosphorus, increase uptake of nitrogen and also synthesize growth
promoting hormones including auxin. The aim of this study was to isolate and
characterize phyllosphere, rhizoplane and rhizosphere micro-organisms from Kenyan
rice with growth promoting habits. In this study whole plant rice samples were
collected from different rice growing regions of Kenya. 76.2%, over 80% and 38.5%
of the bacterial isolates were positive for phosphate solubilization, nitrogenase
activity and IAA production whereas 17.5% and 5% of the fungal isolates were
positive for phosphate solubilization and IAA production respectively. Hence
these micro-organisms have potential for utilization as bio-fertilizers in rice
production.
PMID- 24349942
TI - P2X receptors in neuroglia.
AB - Different types of ionotropic P2X purinoceptors are expressed in all major types
of neuroglia, where they mediate a variety of physiological and pathological
signaling. Cortical astrocytes express specific P2X1/5 heteromeric receptors that
are activated by ongoing synaptic transmission and can trigger fast local
signaling through elevation in cytoplasmic Ca2+ and Na+ concentrations.
Oligodendrocytes express several types of P2X receptors that may control their
development and mediate axonal-glial interactions. In microglia, P2X4 and P2X7
receptors regulate numerous events associated with microglial activation,
motility, and release of proinflammatory factors.
PMID- 24349945
TI - Complementary pharmacokinetic measures to further define the profile of once
daily OROS hydromorphone ER during single-dose and steady-state dosing.
AB - Conventional measures such as maximum plasma concentration (C max ) and area
under the concentration versus time curve (AUC) may be insufficient to fully
describe the pharmacokinetic (PK) profile of extended-release (ER) formulations.
A complementary measure, the half-value duration (HVD), corresponds to the period
of time during a dosing cycle that plasma concentration is at or above half the
value of the maximal concentration (i.e. >=50% C max ). The current post-hoc
analysis uses data from 2 previously published studies comparing the PK profiles
and HVD of OROS hydromorphone ER (16 mg administered once daily) and immediate
release (IR) hydromorphone (4 mg administered every 6 hours), calculating single
dose and steady-state condition values. Bioequivalence was demonstrated between
the 2 formulations. Mean steady-state once-daily OROS hydromorphone ER
concentrations were elevated for most of the 24-hour dosing period and for
significantly longer than with the dose-equivalent IR hydromorphone regimen. The
duration of time spent >=50% C max was, on average, 2.7 times longer at steady
state for the ER formulation, which also maintained steady-state hydromorphone
plasma concentrations, with 65% lower mean degree of fluctuation versus IR
hydromorphone. Both formulations appeared to be well tolerated.
PMID- 24349946
TI - Cryptococcus spp. isolation from excreta of pigeons (Columba livia) in and around
Monterrey, Mexico.
AB - The presence of Cryptococcus spp. has been reported in Mexico's capital city;
however, to our knowledge there are no reports of its presence in the state of
Nuevo Leon located in northeast Mexico. This is presumed to be because the hot
and dry climate in this region does not favor cryptococcal proliferation. This
study confirmed the presence of C. neoformans and C. albidus in 20% (10/50) of
randomly selected fecal samples of pigeons (Columba livia) in the Monterrey
metropolitan area. The presence of this yeast in the state of Nuevo Leon is proof
of its adaptation to the typically hot climate of the area and is consistent with
recent reviews of cryptococcosis cases in several local hospitals. The two
species were identified and characterized through microbiological tests and
molecular identification by DNA extraction and PCR amplification of highly
conserved 18S ribosomal DNA using ITS1 and ITS2 as target regions. The PCR
products were sequenced and compared with those reported in GenBank.
PMID- 24349947
TI - Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective
effects by umbelliferon-alpha-D-glucopyranosyl-(2(I) -> 1(II))-alpha-D
glucopyranoside in streptozotocin induced diabetic rats.
AB - OBJECTIVE: The objective of the present study was to evaluate the effect of
umbelliferon-alpha-D-glucopyranosyl-(2I -> 1II)-alpha-D-glucopyranoside (UFD)
from Aegle marmelos Corr. on serum glucose, lipid profile and free radical
scavenging activity in normal and STZ (streptozotocin) induced diabetic rats.
MATERIALS AND METHODS: Diabetes was induced by single interperitoneal injecting
of streptozotocin (60 mg/kg, i.p.) in the rats. All the rats were divided into
following groups; I - nondiabeteic, II - nondiabetic + UFD (40 mg/kg, p.o.), III
diabetic control, IV - UFD (10 mg/kg, p.o.), V - UFD (20 mg/kg, p.o.), VI - UFD
(40 mg/kg) and VII - glibenclamide (10 mg/kg, p.o.). Serum glucose level and body
weight were determined periodically. Biochemical parameter, antioxidant enzyme
and histopathology study were performed on the day 28. Oral glucose tolerance
test study was performed to identify the glucose utilization capacity. RESULTS:
All the doses of UFD and glibenclamide decrease the level of serum glucose,
glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate and
increased the level of plasma insulin, hexokinase. The UFD doses also showed
effects on antioxidant enzymes viz. superoxide dismutase, catalase and
glutathione peroxidase which were significantly increased and the level of
malonaldehyde was markedly decreased. Histologically study, focal necrosis,
deposition of fats, increased the size of the intercalated disc were observed in
the diabetic rat liver, kidney, heart and pancreas but was less obvious in
treated groups. The mechanism of action of the UFD emerges to be due to increase
the activity of antioxidant enzyme and secretion of pancreatic insulin.
CONCLUSION: Reduction in the FBG (fasting blood glucose), glycated hemoglobin,
glucose-6-phosphatase, fructose-1-6-biphosphate, superoxide dismutase, catalase,
glutathione peroxides, cholesterol, triglyceride, LDL, VLDL levels and
improvement in the level of the plasma insulin, hexokinase, HDL was observed by
the UFD treated rats. The result indicates that UFD has anti-diabetic activity
along with anti hyperlipidemic and antioxidant efficacy and provides a scientific
rationale to be used as an Anti-diabetic agent.
PMID- 24349948
TI - Generation and selection of anti-flagellin monoclonal antibodies useful for
serotyping Salmonella enterica.
AB - In developing countries, bacterial acute gastroenteritis continues to be an
important cause of morbidity and mortality among young children. Salmonellosis
constitutes a major cause of infectious enteritis worldwide, most of them
associated to the consumption of contaminated food products. Traditionally,
Salmonella has been classified in serovars based on varieties of O and H surface
antigens. In the present work we generated and characterized a panel of anti
flagellin monoclonal antibodies (MAbs) in order to select antibodies useful for
detecting the H surface antigen. Four different MAbs were obtained by somatic
hybridization of splenocytes. We found two MAbs that recognised regions of
flagellin conserved among different Salmonella serovars. Other two MAbs
recognised structures restricted to Salmonella enterica sv. Typhimurium, being
one of them suitable for agglutination tests. Using a diverse panel of S.
enterica serovars with different H antigen varieties we confirmed that this MAb
agglutinates specifically S. Typhimurium (antigenic formula: 4,12:i:1,2) or other
serovars expressing flagellar factor i. In conclusion, we generated a valuable
immunochemical tool to be used in simple assays for serotyping of
epidemiologically relevant strains. The capacity to characterize specific strains
and determine the primary sources of Salmonella contamination generate valuable
information of the epidemiology of this microorganism, contributing to the
improvement of public health.
PMID- 24349949
TI - The effects of course length on freestyle swimming speed in elite female and male
swimmers - a comparison of swimmers at national and international level.
AB - Freestyle swimming performance over 50 m, 100 m, 200 m, 400 m, 800 m and 1,500 m
was compared on short (25 m) and long (50 m) course for 92,196 national swimmers
(i.e. annual high score list Switzerland) and 1,104 international swimmers (i.e.
finalists FINA World Championships) from 2000 to 2012. National and international
swimmers of both sexes were on average 2.0 +/- 0.6% faster on short than on long
course. Sex-related differences in swimming speed were greater on short than on
long course for international and national swimmers from 50 m to 800 m. Freestyle
swimming performance improved across years for international swimmers in both
short- and long-course whereas only male national swimmers were able to improve
on short and long course events except for short course events on 800 m and 1,500
m. Performance in national women competing in short and long course events showed
only improvements on 50 m, 100 m and 1,500 m across years. The sex-related
differences in freestyle swimming performance showed no change for international
swimmers. For national swimmers, the sex-related differences in freestyle
swimming performance increased over time in long course from 50 m to 800 m, but
decreased for 1,500 m. In conclusion, elite female and male freestyle swimmers at
national and international level were about 2% faster on 25 m compared to 50 m
course. During the 2000-2012 period, international as well as national swimmers
(i.e. for national level predominantly men) improved freestyle swimming
performance in both long and short course. More vigorous and optimized training
programs focused on muscular force production in combination with efficient
swimming skills might close the performance gap between elite swimmers at
national level and FINA finalists. Further research especially including effects
of anthropometric, biomechanical, and physiological factors is required to fully
understand the effects of course length on freestyle swimming performance, and to
determine whether course length has similar effects on other swim styles.
PMID- 24349950
TI - Asian ascendancy: media in the age of globalization.
AB - This paper aims to investigate the media industry in Asia, with reference to
international standards of media tools, instruments, content, and coverage. We
have also explored factors that may further improve Asian media. We have used an
empirical approach. Our findings revealed that the media in Asian significantly
contribute to expanding cultural knowledge and the exchange of multilateral
dialogues. However, they do not look after the interests of minorities or non
dominating communities. Although the media should be a virtual ambassador, they
often provoke hostilities within regions. Governments own most media outlets in
the developing nations in Asia, and so the media rely on government backing and
are subject to restrictions. International and national regulations connected to
media freedom or constraints should be explored to protect Asian societies. The
practical implications of these negative aspects are that the Asian media does
not help the plights of minorities or minimize the fear of war in the region. The
universal lesson of brotherhood among humanity for all colors and races should be
preached by the media. In this paper, we have concentrated on how Asian media
influence cultural expansion, the exchange of multilateral dialogues, the
interests of minorities, aggression between nations, and generate income for
common citizens.
PMID- 24349952
TI - One-stage laparoscopic surgery for inspissated bile syndrome: case report and
review of surgical techniques.
AB - Inspissated bile syndrome in a 6 week old boy was unresponsive to oral
ursodesoxycholic acid. Intraoperative cholangiography revealed complete
obstruction of the common bile duct. Therefore, the gallbladder fundus was pulled
out through a laparoscopy port site and sutured to the fascia. A catheter was
positioned into the infundibulum for irrigation with ursodesoxycholic acid. At
day 8 complete resolution of the plug and free passage of contrast medium into
the duodenum was documented radiologically. The catheter was removed, skin closed
spontaneously without a second surgery for closure of the gall bladder.
PMID- 24349951
TI - Carbamoylation correlates of cyanate neuropathy and cyanide poisoning: relevance
to the biomarkers of cassava cyanogenesis and motor system toxicity.
AB - We sought to elucidate the protein carbamoylation patterns associated with
cyanate neuropathy relative to cyanide poisoning. We hypothesized that under a
diet deficient in sulfur amino acids (SAA), the carbamoylation pattern associated
with cyanide poisoning is similar to that of cyanate neuropathy. Male rats (6-8
weeks old) were fed a diet with all amino acids (AAA) or 75%-deficiency in SAA
and treated with 2.5 mg/kg/body weight (bw) NaCN, or 50 mg/kg/bw NaOCN, or 1
MUl/g/bw saline, for up to 6 weeks. Albumin and spinal cord proteins were
analyzed using liquid chromatography mass spectrometry (LC-MS/MS). Only NaOCN
induced motor deficits with significant levels of carbamoylation. At Day 14, we
found a diet-treatment interaction effect on albumin carbamoylation (p = 0.07).
At Day 28, no effect was attributed to diet (p = 0.71). Mean number of NaCN
carbamoylated sites on albumin was 47.4% higher relative to vehicle (95% CI:16.7
86.4%). Only NaOCN carbamoylated spinal cord proteins, prominently, under SAA
restricted diet. Proteins targets included myelin basic and proteolipid proteins,
neurofilament light and glial fibrillary acidic proteins, and 2', 3' cyclic
nucleotide 3'-phosphodiesterase. Under SAA deficiency, chronic but not acute
cyanide toxicity may share biomarkers and pathogenetic similarities with cyanate
neuropathy. Prevention of carbamoylation may protect against the neuropathic
effects of cyanate.
PMID- 24349954
TI - Genotypic variation in sorghum [Sorghum bicolor (L.) Moench] exotic germplasm
collections for drought and disease tolerance.
AB - Sorghum [Sorghum bicolor (L.) Moench] grain yield is severely affected by abiotic
and biotic stresses during post-flowering stages, which has been aggravated by
climate change. New parental lines having genes for various biotic and abiotic
stress tolerances have the potential to mitigate this negative effect. Field
studies were conducted under irrigated and dryland conditions with 128 exotic
germplasm and 12 adapted lines to evaluate and identify potential sources for
post-flowering drought tolerance and stalk and charcoal rot tolerances. The
various physiological and disease related traits were recorded under irrigated
and dryland conditions. Under dryland conditions, chlorophyll content (SPAD),
grain yield and HI were decreased by 9, 44 and 16%, respectively, compared to
irrigated conditions. Genotype RTx7000 and PI475432 had higher leaf temperature
and grain yield, however, genotype PI570895 had lower leaf temperature and higher
grain yield under dryland conditions. Increased grain yield and optimum leaf
temperature was observed in PI510898, IS1212 and PI533946 compared to BTx642
(B35). However, IS14290, IS12945 and IS1219 had decreased grain yield and optimum
leaf temperature under dryland conditions. Under irrigated conditions, stalk and
charcoal rot disease severity was higher than under dryland conditions. Genotypes
IS30562 and 1790E R had tolerance to both stalk rot and charcoal rot respectively
and IS12706 was the most susceptible to both diseases. PI510898 showed combined
tolerance to drought and Fusarium stalk rot under dryland conditions. The
genotypes identified in this study are potential sources of drought and disease
tolerance and will be used to develop better adaptable parental lines followed by
high yielding hybrids.
PMID- 24349953
TI - Granular cell tumor of the appendix: a new case and review of the literature.
AB - Granular cell tumor (GCT) is a rare and usually benign lesion of neural /
schwannian origin, most frequently found in middle-age women. The appendicular
involvement is extremely rare: in over half a century only twelve cases have been
reported in the literature, the patients living in America and Europe. Hitherto,
no cases are documented from Africa, Asia and Oceania and no cases of malignant
GCTs of the appendix have been reported. Most patients were diagnosed
preoperatively as having acute appendicitis, whereas in three patients the tumor
was incidentally detected during major abdominal surgery. The GCTs were equally
distributed between mid-appendix and tip, where lymphoid tissue is more abundant
and the anatomical nerve supply is progressively reduced. Moreover, the appendix
surrounding the GCTs is characterized by the presence of chronic inflammatory
cells (histiocytes, plasmocytes, eosinophils, mastocytes) and, therefore, a
chronic inflammation of the appendix may be an antecedent condition favouring the
appearance of GCTs. The GCT of the appendix appears so to be a lesion that
reflects local reactive changes in the neural / schwannian cells, rather than
being a genuine neoplasm. We describe the smallest GCT of the appendix ever
reported, with a detailed literature review supporting its reactive origin in the
lymphatic tissue-rich sites, such as ileo cecal appendix.
PMID- 24349955
TI - Can levels of antioxidants in synovial fluid predict the severity of primary knee
osteoarthritis: a preliminary study.
AB - BACKGROUND: Little is known about differences in amounts of antioxidants or
oxidative stress at different stages of knee osteoarthritis. This study
investigated the relationship between concentrations of antioxidants, iron and
lipid peroxidation in synovial fluid and levels of severity of primary knee
osteoarthritis. MATERIALS AND METHODS: From 2011 to 2013, 23 patients (mean age,
66.7 +/- 7.6 years) with primary knee osteoarthritis were recruited. Patients
were divided into 2 groups based on pre-treatment knee society scores (KSS): n =
9, severe KSS <=46; and n = 14, mild-moderate KSS >46. Synovial fluid was
analyzed to determine levels of antioxidants, iron concentrations and lipid
peroxidation (thiobarbituric acid reactive substances [TBARs]). Baseline data,
including Kellgren- Lawrence radiographic grade, were collected for all patients.
RESULTS: Mean KSS was 49.1 +/- 10.8. Total mean concentrations of antioxidants
were 2.29 +/- 1.71 ng/mL vitamin E and 0.47 +/- 0.51 nmol/mL glutathione (GSH).
Total mean levels of TBARs and iron were 1.20 +/- 0.37 nmol/mL and 2.13 +/- 0.82
MUg/mL, respectively. The mean concentration of vitamin E was inversely related
to severity of knee osteoarthritis (mild-moderate > severe, p = 0.006). There
were no significant differences between the two groups in terms of GSH (p =
0.90), TBARs (p = 0.84) or iron levels (p = 0.27). There was a significant
positive correlation between KSS and vitamin E concentration (r = 0.43, p =
0.04). No significant correlations were shown between KSS and GSH (r = -0.01, p =
0.97), TBARs (r = -0.06, p = 0.81) or iron level (r = 0.28, p = 0.20).
CONCLUSION: Using synovial fluid profiles, vitamin E concentration is an
essential prognostic factor in primary knee osteoarthritis and may act as a basis
for treatment directions. The concentration of vitamin E decreased as the
clinical severity of primary knee osteoarthritis increased.
PMID- 24349956
TI - Effect of microtitanium impregnated tape on the recovery of triceps surae
musculotendinous function following strenuous running.
AB - We previously reported increased running economy and joint range of motion (ROM)
during subsequent exercise performed 48-h following strenuous exercise while
wearing garments containing micro-titanium particles generated from high-pressure
aqueous processing of titanium (AQUA TITAN(TM)). Here we utilised an isolated
plantarflexion triceps surae model and AQUA TITAN-treated flexible tape to
determine if dermal application of the micro-titanium could account for
meaningful changes in functional properties of the musculotendinous unit. In a
randomised double-blind crossover, 20 trained men day 1, baseline measures, AQUA
TITAN or placebo tape covering the triceps surae, intermittent high-intensity
treadmill running; day 2, rest; day 3, post-stress post-treatment outcome
measures. Outcomes comprised: plantarflexion ROM via isokinetic dynamometry;
short latency reflex from electromyography; Achilles tendon stiffness from
isometric dynamometry, ultrasonography (Achilles-medial-gastrocnemius junction),
motion analysis, and force-length modelling. High-intensity exercise with placebo
tape reduced tendon stiffness (-16.5%; 95% confidence limits +/-8.1%; small
effect size), relative to non-taped baseline, but this effect was negligible (
5.9%; +/-9.2%) with AQUA TITAN (AQUA TITAN-placebo difference -11.3%; +/-11.6%).
Change in latency relative to baseline was trivial with placebo (1.6%; +/-3.8%)
but large with AQUA TITAN (-11.3%; +/-3.3%). The effects on ROM with AQUA TITAN
(1.6%; +/-2.0%) and placebo were trivial (-1.6% +/-1.9%), but the small
difference (3.1%; +/-2.7%) possibly greater with AQUA TITAN. AQUA TITAN tape
accelerated the reflex response and attenuated reduced Achilles tendon stiffness
following fatiguing exercise. Altered neuromuscular control of tendon stiffness
via dermal application of micro-titanium treated materials may facilitate
restoration of musculotendinous contractile performance following prior strenuous
exercise.
PMID- 24349958
TI - A novel promising Trichoderma harzianum strain for the production of a
cellulolytic complex using sugarcane bagasse in natura.
AB - Brazil is a major producer of agro-industrial residues, such as sugarcane
bagasse, which could be used as raw material for microbial production of
cellulases as an important strategy for the development of sustainable processes
of second generation ethanol production. For this purpose, this work aimed at
screening for glycosyl hydrolase activities of fungal strains isolated from the
Brazilian Cerrado. Among 13 isolates, a Trichoderma harzianum strain (L04) was
identified as a promising candidate for cellulase production when cultured on in
natura sugarcane bagasse. Strain L04 revealed a well-balanced cellulolytic
complex, presenting fast kinetic production of endoglucanases, exoglucanases and
beta-glucosidases, achieving 4,022, U.L(-1) (72 h), 1,228 U.L(-1) (120 h) and
1,968 U.L(-1) (48 h) as the highest activities, respectively. About 60% glucose
yields were obtained from sugarcane bagasse after 18 hours hydrolysis. This new
strain represents a potential candidate for on-site enzyme production using
sugarcane bagasse as carbon source.
PMID- 24349957
TI - Coconut shells as filling material for anaerobic filters.
AB - In rural areas of developing countries, there is a lack of sanitation services
and the installation of such infrastructure is hampered by the high investment
costs for initial implementation and by the limited availability of qualified
personnel. An alternative to traditional sanitation services include an anaerobic
filter, but the high cost of appropriate filling material can be an obstacle to
its wide-spread implementation. To decrease this construction cost, the objective
of this work was to study the use of coconut shells as filling material for
anaerobic filters. Anaerobic filters were built and filled with the studied
material and operated with up flow and hydraulic retention time of 9 hours. The
reactors provided a removal of 79 +/- 16% in BOD terms, indicating that the
coconut shell filling had efficiency consistent with the literature data. In
addition, the husks were found to retain their tensile strength following use in
the reactors. Coconut husks have more empty bed volume than other low cost
materials, such as crushed stone, nearing properties of traditional materials.
The results of this study indicate that coconut husks may prove to be a low cost
alternative to traditional fillers for anaerobic treatment in rural communities.
PMID- 24349959
TI - Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell
carcinoma correlates with poor prognosis.
AB - N-acetylglucosaminyltransferase V (GnT-V), an enzyme with a key role in the
branching of asparagine-linked oligosaccharides, is strongly linked to tumor
invasion and metastasis of many solid tumors. Here we searched for correlations
between the clinical features of patients with oral squamous cell carcinoma
(OSCC) and GnT-V expression in the tumor, and we studied the feasibility of using
GnT-V as a marker for oral cancer prognosis. Samples from 68 patients with OSCC
were examined by immunohistochemistry using antibodies against GnT-V.
Correlations between the expression level of GnT-V in the tumor and patient
clinical features were statistically analyzed. Positive GnT-V expression was
found in 48 cases (70.6%), and negative GnT-V expression was found in 20 cases
(29.4%). Negative GnT-V expression was associated with mode of invasion by
multiple logistic regression analysis (OR: 3.605; P = 0.048). Biological
characteristics of tumors and the Ki-67 labeling index were higher in tumors with
negative GnT-V expression than in those with positive GnT-V expression, although
the difference was not significant (P = 0.176). Patients with negative GnT-V
expression had significantly shorter survival than those with tumors having
positive GnT-V expression (5-year survival rate, 58.2% and 86.5%, respectively; P
= 0.025). Negative GnT-V expression was a significant unfavorable prognostic
factor for OSCC (hazard ratio, 4.246; P = 0.045). The loss of GnT-V expression is
a likely indicator of tumors with high potential of tumor invasion and poor
prognosis in OSCC patients.
PMID- 24349961
TI - Digital image processing techniques for detecting, quantifying and classifying
plant diseases.
AB - ABSTRACT: This paper presents a survey on methods that use digital image
processing techniques to detect, quantify and classify plant diseases from
digital images in the visible spectrum. Although disease symptoms can manifest in
any part of the plant, only methods that explore visible symptoms in leaves and
stems were considered. This was done for two main reasons: to limit the length of
the paper and because methods dealing with roots, seeds and fruits have some
peculiarities that would warrant a specific survey. The selected proposals are
divided into three classes according to their objective: detection, severity
quantification, and classification. Each of those classes, in turn, are
subdivided according to the main technical solution used in the algorithm. This
paper is expected to be useful to researchers working both on vegetable pathology
and pattern recognition, providing a comprehensive and accessible overview of
this important field of research.
PMID- 24349960
TI - Osteoprotegerin (OPG) as a biomarker for diabetic cardiovascular complications.
AB - Osteoprotegerin (OPG) is a glycoprotein involved in bone metabolisms and with a
regulatory role in immune, skeletal and vascular systems. Recently, circulating
OPG levels have emerged as independent biomarkers of cardiovascular disease (CVD)
in patients with acute or chronic heart disease, as well as in the healthy
population. Furthermore, OPG has been implicated in various inflammations and
linked to diabetes and poor glycaemic control. This review focuses on the
relations between circulating OPG levels and cardiovascular complications, with
special emphasis on diabetic patients. OPG levels were observed to increase
concurrently with the severity of diabetic complications, that is, with the
highest circulating OPG levels observed in diabetic patients dying from CVD.
Although the clinical prognostic use of OPG may seem far away, OPG does look
promising as a biomarker in order to help the cardiologist to a better risk
stratification of the patients.
PMID- 24349962
TI - Does physician continuity within a clinical trial increase retention and
compliance among adolescent smokers?
AB - BACKGROUND: Retention and compliance are hurdles in many clinical trials designed
for adolescents. Factors that may improve these issues in a challenging
population may lead to increased data and power in much needed adolescent
substance abuse research. METHODS: Within a large-scale smoking cessation study
for adolescents, physician continuity (PC) was examined to determine its effect
on retention, compliance, and cessation. RESULTS: In an analysis of 98
participants, participants with physician continuity throughout the study were
more likely to attend more treatment visits and be medication compliant. It was
also found that PC had no effect on participant smoking cessation. CONCLUSIONS:
It appears that PC may be one way to increase retention and compliance within an
adolescent clinical trial, without interfering with the specific aim of the
research study (in this case, smoking cessation).
PMID- 24349965
TI - Atopy and the Development of Chronic Rhinosinusitis in Children with Allergic
Rhinitis.
AB - The role of allergic rhinitis (AR) in the development of chronic rhinosinusitis
(CRS) in children remains unknown. This study demonstrates the degree of atopy,
as reflected by the number of aeroallergen sensitivities or the presence of
atopic comorbidities, is not associated with progression to CRS in the pediatric
age group.
PMID- 24349964
TI - Pathological Gambling: Neuropsychopharmacology and Treatment.
AB - Pathological gambling (PG) affects about 0.2-2% of adults and the impact extends
to family members, employers and society as a whole. Recent research has
identified similarities in the pathophysiologies of PG and substance use
disorders (SUDs). As such, findings regarding SUDs provide a framework for
investigating PG. The aims of the manuscript are two-fold. First, we will briefly
revivew neural systems implicated in PG. Cortico-limbic circuitry involving the
ventral striatum, ventromedial prefrontal cortex, anterior cingulate cortex, and
dorsolateral prefrontal cortex are discussed as are the neurotransmitters
norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma-aminobutyric
acid (GABA). This background will provide a framework for reviewing the
psychopharmacological treatments that have been tested for efficacy and safety in
treating PG. Of medications, the strongest data suggest the efficacy and
tolerability of opioid antagonists in the treatment of PG, and other agents have
varying degree of empirical support. As behavioral therapies have also shown
efficacy, they will be briefly considered as well. Future research is needed to
understand how treatments work in PG and for whom specific treatments might work
best.
PMID- 24349963
TI - Oxazaphosphorine bioactivation and detoxification The role of xenobiotic
receptors.
AB - Oxazaphosphorines, with the most representative members including
cyclophosphamide, ifosfamide, and trofosfamide, constitute a class of alkylating
agents that have a broad spectrum of anticancer activity against many malignant
ailments including both solid tumors such as breast cancer and hematological
malignancies such as leukemia and lymphoma. Most oxazaphosphorines are prodrugs
that require hepatic cytochrome P450 enzymes to generate active alkylating
moieties before manifesting their chemotherapeutic effects. Meanwhile,
oxazaphosphorines can also be transformed into non-therapeutic byproducts by
various drug-metabolizing enzymes. Clinically, oxazaphosphorines are often
administered in combination with other chemotherapeutics in adjuvant treatments.
As such, the therapeutic efficacy, off-target toxicity, and unintentional drug
drug interactions of oxazaphosphorines have been long-lasting clinical concerns
and heightened focuses of scientific literatures. Recent evidence suggests that
xenobiotic receptors may play important roles in regulating the metabolism and
clearance of oxazaphosphorines. Drugs as modulators of xenobiotic receptors can
affect the therapeutic efficacy, cytotoxicity, and pharmacokinetics of
coadministered oxazaphosphorines, providing a new molecular mechanism of drug
drug interactions. Here, we review current advances regarding the influence of
xenobiotic receptors, particularly, the constitutive androstane receptor, the
pregnane X receptor and the aryl hydrocarbon receptor, on the bioactivation and
detoxification of oxazaphosphorines, with a focus on cyclophosphamide and
ifosfamide.
PMID- 24349966
TI - Effects of Fatty Acids and Glycation on Drug Interactions with Human Serum
Albumin.
AB - The presence of elevated glucose concentrations in diabetes is a metabolic change
that leads to an increase in the amount of non-enzymatic glycation that occurs
for serum proteins. One protein that is affected by this process is the main
serum protein, human serum albumin (HSA), which is also an important carrier
agent for many drugs and fatty acids in the circulatory system. Sulfonylureas
drugs, used to treat type 2 diabetes, are known to have significant binding to
HSA. This study employed ultrafiltration and high-performance affinity
chromatography to examine the effects of HSA glycation on the interactions of
several sulfonylurea drugs (i.e., acetohexamide, tolbutamide and gliclazide) with
fatty acids, whose concentrations in serum are also affected by diabetes. Similar
overall changes in binding were noted for these drugs with normal HSA or glycated
HSA and in the presence of the fatty acids. For most of the tested drugs, the
addition of physiological levels of the fatty acids to normal HSA and glycated
HSA produced weaker binding. At low fatty acid concentrations, many of these
systems followed a direct competition model while others involved a mixed-mode
interaction. In some cases, there was a change in the interaction mechanism
between normal HSA and glycated HSA, as seen with linoleic acid. Systems with
only direct competition also gave notable changes in the affinities of fatty
acids at their sites of drug competition when comparing normal HSA and glycated
HSA. This research demonstrated the importance of considering how changes in the
concentrations and types of metabolites (e.g., in this case, glucose and fatty
acids) can alter the function of a protein such as HSA and its ability to
interact with drugs or other agents.
PMID- 24349968
TI - Minimally invasive mitral valve surgery.
PMID- 24349967
TI - Dynamics of childhood growth and obesity: development and validation of a
quantitative mathematical model.
AB - BACKGROUND: Clinicians and policy makers need the ability to predict
quantitatively how childhood bodyweight will respond to obesity interventions.
METHODS: We developed and validated a mathematical model of childhood energy
balance that accounts for healthy growth and development of obesity, and that
makes quantitative predictions about weight-management interventions. The model
was calibrated to reference body composition data in healthy children and
validated by comparing model predictions with data other than those used to build
the model. FINDINGS: The model accurately simulated the changes in body
composition and energy expenditure reported in reference data during healthy
growth, and predicted increases in energy intake from ages 5-18 years of roughly
1200 kcal per day in boys and 900 kcal per day in girls. Development of childhood
obesity necessitated a substantially greater excess energy intake than for
development of adult obesity. Furthermore, excess energy intake in overweight and
obese children calculated by the model greatly exceeded the typical energy
balance calculated on the basis of growth charts. At the population level, the
excess weight of US children in 2003-06 was associated with a mean increase in
energy intake of roughly 200 kcal per day per child compared with similar
children in 1971-74 [corrected]. The model also suggests that therapeutic windows
when children can outgrow obesity without losing weight might exist, especially
during periods of high growth potential in boys who are not severely obese.
INTERPRETATION: This model quantifies the energy excess underlying obesity and
calculates the necessary intervention magnitude to achieve bodyweight change in
children. Policy makers and clinicians now have a quantitative technique for
understanding the childhood obesity epidemic and planning interventions to
control it. FUNDING: Intramural Research Program of the National Institutes of
Health, National Institute of Diabetes and Digestive and Kidney Diseases.
PMID- 24349969
TI - A meta-analysis of MitraClip system versus surgery for treatment of severe mitral
regurgitation.
AB - BACKGROUND: Mitral regurgitation (MR) is the second most common valvular heart
disease after aortic stenosis. Without intervention, prognosis is poor in
patients with severe symptomatic MR. While surgical repair is recommended for
many patients with severe degenerative MR (DMR), as many as 49% of patients do
not qualify as they are at high surgical risk. Furthermore, surgical correction
for functional MR (FMR) is controversial with suboptimal outcomes and significant
perioperative mortality. The percutaneous MitraClip implantation can be seen as a
viable option in high surgical risk patients. The purpose of this meta-analysis
is to compare the safety, clinical efficacy, and survival outcomes of MitraClip
implantation with surgical correction of severe MR. METHODS: Six electronic
databases were searched for original published studies from January 2000 to
August 2013. Two reviewers independently appraised studies, using a standard
form, and extracted data on methodology, quality criteria, and outcome measures.
All data were extracted and tabulated from the relevant articles' texts, tables,
and figures and checked by another reviewer. RESULTS: Overall 435 publications
were identified. After applying selection criteria and removing serial
publications with accumulating number of patients or increased length of follow
up, four publications with the most complete dataset were included for quality
appraisal and data extraction. There was one randomized controlled trial (RCT)
and three prospective observational studies. At baseline, patients in the
MitraClip group were significantly older (P=0.01), had significantly lower LVEF
(P=0.03) and significantly higher EuroSCORE (P<0.0001). The number of patients
with post-procedure residual MR severity >2 was significantly higher in the
MitraClip group compared to the surgical group (17.2% vs. 0.4%; P<0.0001). 30-day
mortality was not statistically significant (1.7% vs. 3.5%; P=0.54), nor were
neurological events (0.85% vs. 1.74%; P=0.43), reoperations for failed MV
procedures (2% vs. 1%; P=0.56), NYHA Class III/IV (5.7% vs. 11.3; P=0.42) and
mortality at 12 months (7.4% vs. 7.3%; P=0.66). CONCLUSIONS: Despite a higher
risk profile in the MitraClip patients compared to surgical intervention, the
clinical outcomes were similar although surgery was more effective in reducing MR
in the early post procedure period. We conclude the non-inferiority of the
MitraClip as a treatment option for severe, symptomatic MR in comparison to
conventional valvular surgery.
PMID- 24349970
TI - A meta-analysis of minimally invasive versus conventional mitral valve repair for
patients with degenerative mitral disease.
AB - BACKGROUND: Minimally invasive mitral valve surgery through a mini-thoracotomy
approach was developed in the mid-1990s as an alternative to conventional
sternotomy, but with reduced trauma and quicker recovery. However, technical
demands and a paucity of comparative data have thus far limited the widespread
adoption of minimally invasive mitral valve repair (MIMVR). Previous meta
analyses have grouped various surgical techniques and underlying valvular disease
aetiologies together for comparison. The present study aimed to compare the
clinical outcomes of MIMVR versus conventional mitral valve repair in patients
with degenerative mitral valve disease. METHODS: A systematic review of the
current literature was performed through nine electronic databases from January
1995 to July 2013 to identify all relevant studies with comparative data on MIMVR
versus conventional mitral valve surgery. Measured endpoints included mortality,
stroke, renal failure, wound infection, reoperation for bleeding, aortic
dissection, myocardial infarction, atrial fibrillation, readmission within 30
days, cross clamp time, cardiopulmonary bypass time and durations of intensive
care unit (ICU) stay and overall hospitalization. Echocardiographic outcomes were
also assessed when possible. RESULTS: Seven relevant studies were identified
according to the predefined study selection criteria, including one randomized
controlled trial and six retrospective studies. Meta-analysis of clinical
outcomes did not identify any statistically significant differences between MIMVR
and conventional mitral valve repair. The duration of ICU stay was significantly
shorter for patients who underwent MIMVR, but this did not translate to a shorter
hospitalization period. Patients who underwent MIMVR required longer cross clamp
time as well as cardiopulmonary bypass time. Both surgical techniques appeared to
achieve satisfactory echocardiographic outcomes. Pain-related outcomes was
assessed in one study and reported significantly less pain for patients who
underwent MIMVR. However, this limited data was not suitable for meta-analysis.
CONCLUSIONS: The existing literature has limited data on comparative outcomes
after MIMVR versus conventional mitral valve repair for patients with
degenerative disease. From the available evidence, there are no significant
differences between the two surgical techniques in regards to clinical outcomes.
Patients who underwent MIMVR required longer cardiopulmonary bypass and cross
clamp times, but the duration of stay in the ICU was significantly shorter than
conventional mitral valve repair.
PMID- 24349971
TI - Systematic review of robotic minimally invasive mitral valve surgery.
AB - BACKGROUND: Robotic telemanipulators have evolved to assist the challenges of
minimally invasive mitral valve surgery (MVS). A systematic review was performed
to provide a synopsis of the literature, focusing on clinical outcomes and cost
effectiveness. METHOD: Structured searches of MEDLINE, Embase, and Cochrane
databases were performed in August 2013. All original studies except case-reports
were included in qualitative review. Studies with >=50 patients were presented
quantitatively. RESULTS: After applying inclusion and exclusion criteria to the
search results, 27 studies were included in qualitative review, 16 of which had
>=50 patients. All studies were observational in nature, and thus the quality of
evidence was rated low to medium. Patients generally had good left ventricular
performance, were relatively asymptomatic, and mean patient age ranged from 52.6
58.4 years. Rates of intraoperative outcomes ranged from: 0.0-9.1% for conversion
to non-robotic surgery, 106+/-22 to 188.5+/-53.8 min for cardiopulmonary bypass
(CPB) time and 79+/-16 to 140+/-40 min for cross-clamp (XC) time. Rates of short
term postoperative outcomes ranged from: 0.0-3.0% for mortality, 0.0-3.2% for
myocardial infarction (MI), 0.0-3.0% for permanent stroke, 1.6-15% for pleural
effusion, 0.0-5.0% for reoperations for bleeding, 0.0-0.3% for infection, and 1.1
6% for prolonged ventilation (>48 hours), 1.5-5.4% for early repair failure,
12.3+/-6.7 to 36.6+/-24.7 hours for intensive care length of stay, 3.1+/-0.3 to
6.3+/-3.9 days for hospital length of stay (HLOS) and 81.7-97.6% had no or
trivial mitral regurgitation (MR) before discharge. CONCLUSIONS: All subtypes of
mitral valve prolapse are repairable with robotic techniques. CPB and XC times
are long, and novel techniques such as the Cor-Knot, Nitinol clips or running
sutures may reduce the time required. The overall rates of early postoperative
mortality and morbidity are low. Improvements in postoperative quality of life
(QoL) and expeditious return to work offset the increase in equipment and
intraoperative cost. Evidence for long-term outcomes is as yet limited.
PMID- 24349973
TI - Keynote Lecture-Transmitral hypertrophic obstructive cardiomyopathy (HOCM)
repair.
AB - Hypertrophic obstructive cardiomyopathy (HOCM) is a heterogenous disease causing
obstruction of the left and/or right ventricular outflow tract (LVOT and/or RVOT,
respectively). The main symptoms include dyspnea on exertion and syncope, and in
severe cases, subsequent development of heart failure symptoms with end stage
heart failure occurs. In a certain number of patients, surgical intervention is
required since pharmacological and/or interventional treatment using
transcoronary ablation of septal hypertrophy (TASH) does not relieve symptoms.
The primary goal of any surgical technique is to relieve LVOT obstruction, avoid
the occurrence and/or recurrence of systolic anterior movement (SAM) of the
anterior mitral leaflet (AML) and-if present-reduce mitral valve (MV)
regurgitation. Depending on the configuration of LVOT obstruction, myectomy
with/without MV replacement has been the "gold standard" in surgical treatment of
HOCM. However, considering the known disadvantages of artificial valves, MV
preserving techniques will improve postoperative outcomes and decrease major
adverse events in the long term. We describe the currently available operative
strategies for treatment of HOCM. Special consideration is given to minimally
invasive access with subaortic LVOT myectomy and complete resuspension of the AML
to treat both HOCM and MV regurgitation.
PMID- 24349972
TI - Custodiol for myocardial protection and preservation: a systematic review.
AB - INTRODUCTION: Custodiol cardioplegia is attractive for minimally invasive cardiac
surgery, as a single dose provides a long period of myocardial protection.
Despite widespread use in Europe, there is little data confirming its efficacy
compared with conventional (blood or crystalloid) cardioplegia. There is similar
enthusiasm for its use in organ preservation for transplant, but also a lack of
data. This systematic review aimed to assess the evidence for the efficacy of
Custodiol in myocardial protection and as a preservation solution in heart
transplant. METHODS: Electronic searches were performed of six databases from
inception to October 2013. Reviewers independently identified studies that
compared Custodiol with conventional cardioplegia (blood or extracellular
crystalloid) in adult patients for meta-analysis; large case series that reported
results using Custodiol were analyzed. Next, we identified studies that compared
Custodiol with other organ preservation solutions for organ preservation in heart
transplant. RESULTS: Fourteen studies compared Custodiol with conventional
cardioplegia for myocardial protection in adult cardiac surgery. No difference
was identified in mortality; there was a trend for increased incidence of
ventricular fibrillation in the Custodiol group that did not reach statistical
significance. No difference was identified in studies that compared Custodiol
with other solutions for heart transplant. CONCLUSIONS: Despite widespread
clinical use, the evidence supporting the superiority of Custodiol over other
solutions for myocardial protection or organ preservation is limited. Large
randomised trials are required.
PMID- 24349974
TI - Cross-sectional survey on minimally invasive mitral valve surgery.
AB - BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) has become a standard
technique to perform mitral valve surgery in many cardiac centers. However, there
remains a question regarding when MIMVS should not be performed due to an
increased surgical risk. Consequently, expert surgeons were surveyed regarding
their opinions on patient factors, mitral valve pathology and surgical skills in
MIMVS. METHODS: Surgeons experienced in MIMVS were identified through an
electronic search of the literature. A link to an online survey platform was sent
to all surgeons, as well as two follow-up reminders. Survey responses were then
submitted to a central database and analyzed. RESULTS: The survey was completed
by 20 surgeons. Overall results were not uniform with regard to contraindications
to performing MIMVS. Some respondents do not consider left atrial enlargement
(95% of surgeons), complexity of surgery (75%), age (70%), aortic calcification
(70%), EuroSCORE (60%), left ventricular ejection fraction (55%), or obesity
(50%) to be contraindication to surgery. Ninety percent of respondents believe
more than 20 cases are required to gain familiarity with the procedure, while 85%
believe at least one MIMVS case needs to be performed per week to maintain
proficiency. Eighty percent recommend establishment of multi-institutional
databases and standardized surgical mentoring courses, while 75% believe MIMVS
should be incorporated into current training programs for trainees. CONCLUSIONS:
These results suggest that MIMVS has been accepted as a treatment option for
patients with mitral valve pathologies according the expert panel. Initial
training and continuing practice is recommended to maintain proficiency, as well
as further research and formalization of training programs.
PMID- 24349975
TI - Total percutaneous femoral vessels cannulation for minimally invasive mitral
valve surgery.
AB - BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) has experienced
several technological changes in the last two decades. Our aim was to describe
one of the most recent improvements, the utilization of a total percutaneous
femoral vessels cannulation technique during MIMVS. METHODS: We performed a
retrospective observational analysis of this technique among 300 consecutive
MIMVS patients, with particular focus on cannulation aspects of MIMVS, its
success rate and potential complications. RESULTS: From October 2008 to December
2012, 300 patients (60% males) were operated on. Mean age was 62.9+/-16.4 years.
Indications for operation included mitral valve repair (93%) and mitral valve
replacement (7%). Two femoral arterial catheterizations failed and required
conversion to sternotomy. The complications on the arterial side were: 5 (1.6%)
cases of bleeding during the introduction of Prostar leading to a preoperative
surgical hemostasis; 2 (0.6%) retroperitoneal bleeds during cardiopulmonary
bypass requiring difficult surgical control but with an uneventful follow-up; 6
(2%) bleeding episodes after removal of the arterial cannula easily controlled by
direct surgical revision; 1 (0.3%) arterio-venous fistula requiring a surgical
correction on postoperative day 32; 1 (0.3%) patient had a transitory
claudication due to a superficial femoral artery thrombosis progressively
compensated by the collateral circulation. There were no postoperative bleeding
complications. There were no other complications linked to the femoral
cannulations or to the groin occurred during the follow-up. The percentage of
uneventful arterial cannulations was 80% among the first 50 patients (N=10 out of
50) and 98.8% thereafter (N=3 out of 250). CONCLUSIONS: Total percutaneous
femoral vessels cannulation technique is particularly suitable for MIMVS with a
high success rate and few complications after a short learning curve. With the
advent of the percutaneous approach, the traditional complications of the groin
incision have completely disappeared in modern operations with no groin
infection, hematoma or lymphocele.
PMID- 24349976
TI - Minimally invasive mitral valve surgery: "The Leipzig experience".
AB - BACKGROUND: Minimally invasive mitral valve surgery has become a routine
procedure at our institution. The present study analyzed the early and long-term
outcomes of patients undergoing minimally invasive mitral valve surgery over the
last decade, with special focus on mitral valve repairs (MVRp). METHODS: The
preoperative variables, intraoperative data and postoperative outcomes of
patients undergoing minimally invasive mitral valve surgery were prospectively
collected in our database from May 1999 to December 2010. The survival and
freedom from reoperation were evaluated with life tables and Kaplan-Meier
analyses. RESULTS: A total of 3,438 patients underwent minimally invasive mitral
valve surgery, of which 2,829 were MVRps and 609 were mitral valve replacements
(MVR). Forty-five patients (1.6%) required MVR due to failure of repair. The mean
age was 60.3+/-13 years. More than a third of patients underwent concomitant
procedures like tricuspid valve surgery, atrial septal defect (ASD) closure and
cryoablation. The rate of conversion to sternotomy was less than 1.4%. The 30-day
mortality was 0.8%. The 5- and 10-year survival of all patients (MVR and MVRp)
undergoing minimally invasive mitral valve surgery was 85.7+/-0.6% and 71.5+/
1.2%, respectively. For MVRp, the survival was 87.0+/-0.7% and 74.2+/-1.4% at 5
and 10 years, respectively. Freedom from reoperation was 96.6+/-0.4% and 92.9+/
0.9% at 5 and 10 years, respectively. CONCLUSIONS: Minimally invasive MVRp can be
performed safely and effectively with very few perioperative complications. The
early and long-term outcomes in these patients are acceptable.
PMID- 24349977
TI - Rate of repair in minimally invasive mitral valve surgery.
AB - BACKGROUND: Valve repair has been shown to be the method of choice in the
treatment of patients with severe mitral valve regurgitation. Minimally invasive
surgery has raised skepticism regarding the rate of repair especially for
supposedly complex lesions, when anterior leaflet involvement or bileaflet
prolapse is present. We sought to review our experience of all our patients
presenting with degenerative mitral valve regurgitation and operated on minimally
invasively. METHOD: From September 2006 to December 2012, 842 patients (mean age
56.12+/-11.62 years old) with degenerative mitral valve regurgitation and
anterior leaflet (n=82, 9.7%), posterior leaflet (n=688, 81.7%) and bileaflet
(n=72, 8.6%) prolapses were operated on using a minimally invasive approach.
RESULTS: 836 patients had a valve repair (99.3%) and received a concomitant ring
annuloplasty (mean size, 33.7; range, 28-40). Six patients (0.7%) underwent valve
replacement. Two patients had a re-repair due to MR progression or infective
endocarditis. Thirty-day mortality was 0.2% (two patients). There were 60 major
adverse events (MAE) (7.1%). CONCLUSIONS: A minimally invasive approach allows
repair of almost all degenerative valves with good short-term outcomes in a
tertiary referral center, when using proven and efficient surgical techniques.
PMID- 24349978
TI - Concomitant tricuspid valve repair in patients with minimally invasive mitral
valve surgery.
AB - BACKGROUND: The aim of this study was to investigate the 10-year Leipzig
experience with minimally invasive mitral valve (MIMV) surgery in combination
with tricuspid valve (TV) surgery. METHODS: Between January 2002 and December
2011, a total of 441 patients with mitral valve (MV) dysfunction and concomitant
TV regurgitation (TR) underwent MIMV surgery at the Leipzig Heart Center. The
mean age was 68.7+/-10.0 years, mean LVEF was 56.7%+/-13.1% and 184 patients
(41.7%) were male. The Average logEuroSCORE was 8.3%+/-7.2%, and patients had an
average follow-up of 3.4+/-2.4 years. RESULTS: Pre-discharge echocardiography
showed no or mild mitral regurgitation (MR) in 95.1% and no or mild TR in 84.1%.
Overall 30-day mortality was 4.3% with nineteen deaths. Five-year survival was
77.2%+/-2.5%. Five-year freedom from TV-related reoperation was 91.0%+/-1.8%.
CONCLUSIONS: Our 10-year experience show that MIMV surgery in combination with TV
surgery can be performed routinely with good peri- and post-operative results.
Our observations support current recommendations to perform concomitant TV
repair, particularly if tricuspid annular dilation is present.
PMID- 24349979
TI - Minimally invasive mitral valve surgery in octogenarians-a brief report.
PMID- 24349980
TI - Barlow's mitral valve disease: results of conventional and minimally invasive
repair approaches.
AB - Barlow's valve is a clinically important form of degenerative mitral valve (MV)
disease that is characterized by unique clinical, echocardiographic and
pathological features. Successful and durable repair of Barlow's MV represents a
clinical challenge for most cardiac surgeons. An armamentarium of different MV
repair techniques may be required, resectional, neochordal or plicational
techniques. Although conventional sternotomy remains the mainstay approach for MV
surgery in the majority of cardiac surgery centers, minimally invasive surgery
(MIS) is becoming increasingly accepted amongst patients, referring physicians
and practicing cardiac surgeons. As surgical approaches, instrumentation and
operative experience develop, select centers are now performing MIS MV surgery
for nearly all MV patients. Although successful Barlow's MV repair is more
complex than that for most degenerative pathologies, several centers have
published relatively large series of MIS MV repair for Barlow's disease. In this
review article, we highlight and compare the early and long-term results of
conventional and minimally invasive approaches to Barlow's and bileaflet mitral
prolapse disease. Recent studies from various large volume centers around the
world have demonstrated equivalent safety and efficacy outcomes of the MIS
approach compared to conventional sternotomy surgery. In addition, MIS MV surgery
may allow patients to benefit from a cosmetically appealing incision, a faster
recovery and a quicker return to normal activities. However, a definite learning
curve has been demonstrated for MIS MV surgery. If a patient with Barlow's
disease or other complex MV pathology desires to undergo MIS MV surgery, referral
to a center and/or surgeon with extensive experience in MIS MV surgery is
recommended.
PMID- 24349981
TI - How to start a minimal access mitral valve program.
AB - The seven pillars of governance established by the National Health Service in the
United Kingdom provide a useful framework for the process of introducing new
procedures to a hospital. Drawing from local experience, the author present
guidance for institutions considering establishing a minimal access mitral valve
program. The seven pillars of governance apply to the practice of minimally
invasive mitral valve surgery, based on the principle of patient-centred
practice. The author delineate the benefits of minimally invasive mitral valve
surgery in terms of: "clinical effectiveness", including reduced length of
hospital stay, "risk management effectiveness", including conversion to
sternotomy and aortic dissection, "patient experience" including improved
cosmesis and quicker recovery, and the effectiveness of communication, resources
and strategies in the implementation of minimally invasive mitral valve surgery.
Finally, the author have identified seven learning curves experienced by surgeons
involved in introducing a minimal access mitral valve program. The learning
curves are defined as: techniques of mitral valve repair, Transoesophageal
Echocardiography-guided cannulation, incisions, instruments, visualization,
aortic occlusion and cardiopulmonary bypass strategies. From local experience,
the author provide advice on how to reduce the learning curves, such as
practising with the specialised instruments and visualization techniques during
sternotomy cases. Underpinning the NHS pillars are the principles of systems
awareness, teamwork, communication, ownership and leadership, all of which are
paramount to performing any surgery but more so with minimal access surgery, as
will be highlighted throughout this paper.
PMID- 24349982
TI - How do we use imaging to aid considerations for intervention in patients with
severe mitral regurgitation?
AB - Increasing life expectancy and comorbid conditions, like obesity, especially in
industrialized countries, have led to Valvular Heart Disease (VHD) becoming a
major epidemic. Mitral valve disease currently accounts for nearly 10% of
Valvular Heart Disease in industrialized countries worldwide. It is a known fact
that, left untreated, degenerative mitral valve disease not only shortens an
individual's life, but is also associated with increased morbidity. Despite
current guidelines, there is often marked delay in appropriately sending patients
for consideration of surgical intervention-interventions that when performed well
can dramatically restore patients to a more normal lifespan. The critical
question is really not what the severity of the mitral regurgitation is, but what
the effect of the mitral regurgitation is on the heart. Modern day
echocardiography utilizing Transthoracic Echo, Stress Echo, and Transesophageal
Echo, can provide the clinician and the surgeon with six key factors that when
taken together provide clear direction as to the proper timing for consideration
for mitral valve repair. Thinking of these in an integrative fashion, the
clinician and the surgeon can more appropriately time proper surgical
intervention in primary degenerative mitral regurgitation.
PMID- 24349983
TI - New concepts for mitral valve imaging.
AB - The high complexity of the mitral valve (MV) anatomy and function is not yet
fully understood. Studying especially the dynamic movement and interaction of MV
components to describe MV physiology during the cardiac cycle remains a
challenge. Imaging is the key to assessing details of MV disease and to studying
the lesion and dysfunction of MV according to Carpentier. With the advances of
computational geometrical and biomechanical MV models, improved quantification
and characterization of the MV has been realized. Geometrical models can be
divided into rigid and dynamic models. Both models are based on reconstruction
techniques of echocardiographic or computed tomographic data sets. They allow
detailed analysis of MV morphology and dynamics throughout the cardiac cycle.
Biomechanical models aim to simulate the biomechanics of MV to allow for
examination and analysis of the MV structure with blood flow. Two categories of
biomechanical MV models can be distinguished: structural models and fluid
structure interaction (FSI) models. The complex structure and dynamics of MV
apparatus throughout the cardiac cycle can be analyzed with different types of
computational models. These represent substantial progress in the diagnosis of
structural heart disease since MV morphology and dynamics can be studied in
unprecedented detail. It is conceivable that MV modeling will contribute
significantly to the understanding of the MV.
PMID- 24349984
TI - Value of transesophageal echocardiography (TEE) guidance in minimally invasive
mitral valve surgery.
AB - The role of intraoperative transesophageal echocardiography (TEE) has increased
tremendously since its first use in 1979. Today intraoperative TEE is a class I
indication for surgical mitral valve reconstruction for evaluation of mitral
valve pathology, graduation of mitral regurgitation and detection of potential
risk factors as well as post-repair assessment. Real-time three-dimensional TEE
offers anatomical visualization of the mitral valve apparatus, fundamental for
virtual surgical planning of proper annuloplasty ring size. As minimally invasive
and even off-pump techniques for mitral valve repair become more popular, image
guidance by intraoperative TEE will play an essential role.
PMID- 24349985
TI - Myocardial protection during minimally invasive mitral valve surgery: strategies
and cardioplegic solutions.
AB - Effective myocardial protection and perfusion strategies during minimally
invasive mitral valve surgery (Mini-MV) have evolved over the last decade. Our
institutional approach for right-sided Mini-MV has been standardized over the
last 15 years in more than 4,500 cases. Cardiopulmonary bypass (CPB) is usually
instituted by right-sided femoral arterial and venous cannulation with additional
cannulation of the right jugular vein in patients with a body weight greater than
75 kg or when a concomitant tricuspid valve (TV) procedure and/or atrial septal
defect closure is performed. A single dosage of crystalloid-based cardioplegia
[Custodial- histidine-trypthophan-ketoglutarate (Custodial-HTK)] administered via
the aortic root in combination with moderate hypothermia (34-35 degrees C) has
become the standard of care for induction and maintenance of myocardial
protection at our institution. The present article highlights and discusses the
principal techniques of myocardial protection for Mini-MV.
PMID- 24349986
TI - Chordae replacement versus leaflet resection in minimally invasive mitral valve
repair.
AB - For many years, the quadrangular resection technique first proposed by Carpentier
has become the gold standard for repair of posterior leaflet prolapse of the
mitral valve (MV). Although this "resection" technique and its modifications are
safe and very effective, they do not respect the anatomy of the MV and the
physiological role of the posterior leaflet. Therefore some new techniques,
aiming to preserve MV leaflets to a different extent, have been proposed. With
the use of expanded polytetrafluoroethylene (ePTFE), neochordae leaflet
preserving techniques for posterior MV prolapse treatment have emerged. The aim
of these techniques is to support the free edge of the prolapsing segments and
thereby restore the physiologic function of the MV. A simplified modification of
this technique using premeasured ePTFE loops ("loop technique") was successfully
introduced to ease the implantation of neochordae, especially in the setting of
minimally invasive MV surgery. While "resection" techniques are associated with
excellent long-term results, there is evolving evidence in favor of "non
resection" techniques supporting the concept of a "respect rather than resect"
approach.
PMID- 24349987
TI - Robotic mitral valve surgery-current status and future directions.
AB - Robotic mitral valve surgery is the most common robotic cardiac procedure
performed today. Benefits include smaller, less invasive incisions resulting in
less pain, shorter length of hospital stay, improved cosmesis, quicker return to
preoperative level of functional activity, and decreased blood transfusion
requirements. The history and evolution of robotic mitral valve surgery is
detailed in this article. Our institution has performed over 800 robotic mitral
valve surgeries, and our technique and outcomes are described. Outcomes and
operative times are similar to that for sternotomy and minimally invasive
approaches to mitral valve surgery. The benefits and limitations of robotic
mitral valve surgery are compared with conventional approaches, and future
directions are also discussed.
PMID- 24349988
TI - Minimally invasive valve sparing mitral valve repair-the loop technique-how we do
it.
AB - Mitral valve insufficiency is the second most common heart valve disease, with
untreated regurgitation leading to enlargement of the left atrium (LA), atrial
fibrillation and heart failure. Besides functional regurgitation, the main cause
is degenerative valve disease with elongation of the chordae tendineae and
prolapsing of the leaflets. Surgical repair is the gold standard therapy for
mitral valve insufficiency today. Recently, the implantation of neochordae (the
"loop-technique") has been established and is the preferred technique in many
centres including ours. Results of surgical mitral valve repair are good with low
rates of re-intervention and mortality. With minimally invasive techniques,
patient satisfaction is high and hospital stay is short. In conclusion, mitral
valve repair should be the preferred strategy in patients with symptomatic mitral
valve insufficiency or with asymptomatic mitral valve insufficiency in accordance
with the guidelines. Modern repair techniques like neo-chord implantation with
the loop-technique combined with minimally invasive access routes result in low
mortality and morbidity and short hospital stay as well as high patient
satisfaction.
PMID- 24349989
TI - Video-atlas on minimally invasive mitral valve surgery-the Mohr technique.
PMID- 24349990
TI - Video-atlas on minimally invasive mitral valve surgery-The David Adams technique.
AB - Median sternotomy has unquestionably evolved over recent decades. Modern
sternotomy involves a 7-8 cm lower midline skin incision, tunneling of the
subcutaneous tissues with subsequent creation of myocutaneous flaps, full
sternotomy, and standard cardiopulmonary bypass techniques with central
cannulation. In experienced centers, modern sternotomy may achieve all the goals
of minimally invasive surgery, including excellent cosmesis, excellent
postoperative pain control, low rates of bleeding and transfusion (our re
exploration rate for bleeding is <1%), and the ability to perform any
reconstructive technique that would be used in a standard sternotomy, with very
high repair rates (our most recent series documented a repair rate exceeding 99%
in an all-comers population of degenerative disease regardless of complexity).
PMID- 24349991
TI - Minimally invasive repair of posterior leaflet mitral valve prolapse with the
"respect" approach.
PMID- 24349992
TI - Central aortic cannulation for minimally invasive mitral valve surgery through
right minithoracotomy.
PMID- 24349993
TI - Optimizing outcomes of robotic mitral valve repair for all prolapse anatomy: the
Suri-Burkhart technique.
PMID- 24349994
TI - Video-atlas on robotically assisted mitral valve surgery.
PMID- 24349995
TI - Safeguards and pitfalls in minimally invasive mitral valve surgery.
AB - Minimally invasive mitral valve surgery has been established in many institutions
worldwide. Appropriate indications and patient selection for this procedure must
be based on a thorough understanding of its limitations and specific pitfalls.
Particular risks can be minimized with careful attention to detail when planning
and performing the surgery. The following chapter offers a stepwise description
of the procedure; we point out particular advantages, discuss our rationale for
certain steps, as well as focus on potential dangers of minimally invasive mitral
valve surgery. Several graphics have also been provided to illustrate our
approach and demonstrate important structural and anatomical concepts of the
mitral valve apparatus.
PMID- 24349996
TI - Conversion rate and contraindications for minimally invasive mitral valve
surgery.
PMID- 24349997
TI - Systematic Review Protocol: surgical ablation for atrial fibrillation during
mitral valve surgery.
PMID- 24349999
TI - Minimally invasive mitral valve surgery.
PMID- 24349998
TI - Systematic review protocol: surgical ablation versus catheter ablation for atrial
fibrillation.
PMID- 24350000
TI - Retrograde femoral arterial perfusion and stroke risk during minimally invasive
mitral valve surgery: is there cause for concern?
AB - Recent data have suggested that retrograde arterial perfusion (RAP) during
minimally invasive mitral valve surgery (MIMVS) is associated with a higher
stroke rate than sternotomy approaches. To assess whether there is genuine cause
for concern, we examine the strengths and weaknesses of this data. A multitude of
confounding factors obfuscate interpretation of the data including imprecise
definitions of MIMVS, the effect of the substantial learning curve, retrospective
comparisons of small historic cohorts with baseline differences and differing
risk profiles for atherosclerosis, different methods of aortic occlusion and lack
of reporting of peripheral vascular disease (PVD)/aortic assessment in patient
populations. In patients with severe (grades IV and V) aortic arch/ascending
aortic atherosclerosis, RAP has clearly been shown to be associated with an
increase in risk of cerebral embolic complications. It would be reasonable to
assume that grades IV/V atheroma anywhere along the aorto-iliac axis (from
femoral cannulation site to carotid arteries) may also increase the risk of
stroke. Hence those at risk of severe atherosclerotic vascular disease should be
screened to fully assess the aortoiliac axis. Apart from this patient group,
there is no convincing evidence (without confounding variables) that retrograde
perfusion per se during minimally invasive mitral surgery increases the risk of
stroke. This may be due to the largely differing aetiologies of vascular and
mitral degenerative disease.
PMID- 24350001
TI - [Not Available].
PMID- 24350002
TI - Progressive cribriform and zosteriform hyperpigmentation: Where are we at
present?
PMID- 24350003
TI - Nanocarriers and nanoparticles for skin care and dermatological treatments.
AB - NANOTECHNOLOGY (NANO: One billionth) is a novel arena with promising applications
in the field of medicine, especially pharmaceuticals for safe and targeted drug
delivery. The skin is a phenomenal tool for investigation of nanocarriers for
drug delivery for topical and dermatological application. The physicochemical
characteristics of the nanoparticles, such as rigidity, hydrophobicity, size and
charge are crucial to the skin permeation mechanism. Many nanocarriers such as
polymeric, inorganic and lipid nanoparticles and nanoemulsions have been
developed and some like carbon nanotubes and fullerenes still need further
exploration for future use in skin care and dermatological treatments. Risks of
nanopollution and cytotoxicity also need to be kept in mind while exploring
various nanoparticles for medical use.
PMID- 24350004
TI - Interesting and unusual clinical presentations in leprosy at a referral center.
AB - BACKGROUND: Leprosy is a disease of declining global endemicity but is still an
important health-care problem in India. Pure neural leprosy is an important
subset of presentations of leprosy in India. Leprosy is a known disease of the
skin and nerves, but cases of pure neural involvement are relatively less. We
hereby present 10 cases of pure neural leprosy in which the diagnosis of leprosy
was difficult with routine methods. MATERIALS AND METHODS: The study was
conducted at the main referral center and satellite clinics of our organization.
A retrospective analysis of patient records for the last four years was
undertaken to identify patients presenting with predominantly neurological
manifestations and uncommon presentations including those without skin lesions.
The medical records of the patients were used as source of data. All the patients
were subjected to a detailed clinical examination and bacteriological examination
with slit-skin smears. Investigations like nerve biopsy, electromyography, and
nerve conduction studies were done in patients with diagnostic difficulties.
RESULTS: Patients presented with neurological symptoms like paresthesias (60%),
diminished sensations (40%), nonhealing ulcers (30%), and blisters (20%). All
except one had thickened nerves on clinical examination. Slit-skin smear was
negative in all but one patient. Nerve biopsy confirmed the diagnosis of leprosy
in seven cases. CONCLUSION: Pure neural leprosy is difficult to diagnose with
routine methods. The diagnosis should be considered, especially by neurologists
and dermatologists, who are more likely to see such patients with predominant
neural manifestations. The diagnosis should be confirmed with nerve biopsy to
prevent delay in therapy and associated complications.
PMID- 24350005
TI - Study of oxidative stress in peripheral blood of Indian vitiligo patients.
AB - BACKGROUND: Vitiligo is an acquired skin disease that involves the interplay of
complex genetic, immunological, neural and self-destructive mechanisms in its
pathogenesis. According to autocytotoxic hypothesis, oxidative stress has been
suggested to be the initial pathogenic event in melanocyte degeneration.
OBJECTIVES: The aim of our investigation was to evaluate the role of oxidative
stress by studying the role of catalase (CAT) in the destruction of melanocytes
in patients with vitiligo and compare the same in healthy normal controls.
MATERIALS AND METHODS: We determined the serum catalase enzyme by ELISA method.
The catalase activity was studied in two groups, Group I-localized vitiligo: (i)
active stage, (ii) static or inactive stage and Group II-generalized vitiligo:
(i) active stage, (ii) static or inactive stage patients, and the levels were
compared with healthy controls. RESULTS: Group I active stage patients showed
significant difference in the catalase levels with a P < 0.044 when compared with
healthy controls, whereas Group II static stage patients did not show any
significant difference (P < 0.095) although the catalase activity was increased.
CONCLUSION: Our study could not explain the cause of melanocyte damage in
patients in the active stage of the disease. The increase in the oxidative stress
as detected by catalase activity was more significant in Group I active disease
than Group II active disease patients although the levels were higher than the
healthy normals. This is the first study conducted on active and static stage of
vitilgo in India. It is possible that the number of compounds of hydrogen
peroxide produced is not balanced by the production of catalase in the body.
PMID- 24350006
TI - Androgenetic alopecia and risk of coronary artery disease.
AB - BACKGROUND: Androgenetic alopecia (AGA) or male pattern baldness (MPB) has been
found to be associated with the risk of coronary artery disease (CAD). The well
known risk factors are family history of CAD, hypertension, increased body mass
index (BMI), central obesity, hyperglycemia, and dyslipidemia. The newer risk
factors are serum lipoprotein-a (SL-a), serum homocysteine (SH), and serum
adiponectin (SA). AIM: Identifying individuals at risk of CAD at an early age
might help in preventing CAD and save life. Hence, a comparative study of CAD
risk factors was planned in 100 males of AGA between the age of 25 and 40 years
with equal number of age- and sex-matched controls. MATERIALS AND METHODS:
Patients of AGA grade II or more of Hamilton and Norwood (HN) Scale and controls
were examined clinically and advised blood test. The reports were available for
fasting blood sugar (FBS), serum total serum cholesterol (SC) in 64 cases, 64
controls; lipoproteins (high, low, very low density, HDL, LDL, VLDL), serum
triglycerides (ST) in 63 cases, 63 controls; SL-a in 63 cases, 74 controls; SH in
56 cases, 74 controls; and SA in 62 cases, 74 controls. RESULTS: In these cases
family history (FH) of AGA and CAD was significantly high. The blood pressure
(BP) was also found to be significantly high in the cases. The difference of mean
serum HDL, LDL, VLDL, ST, SH, and SL-a in cases and controls were statistically
significant and with increasing grade of AGA, the risk factors also increased.
CONCLUSION: Patients with AGA appear to be at an increased risk of developing
CAD, therefore, clinical evaluation of cases with AGA of grade II and above may
be of help in preventing CAD in future.
PMID- 24350007
TI - Necrobiosis lipoidica: A clinicopathological study in the Indian scenario.
AB - CONTEXT: Necrobiosis lipoidica (NL) is a chronic granulomatous dermatitis that is
commonly associated with diabetes mellitus. Most of the current knowledge about
this entity is from western literature. AIMS: This study evaluates the
clinicohistological features of NL in an Indian scenario. MATERIALS AND METHODS:
We retrospectively reviewed clinical features, associated comorbidities, and
biopsies of all patients with NL over a period of one year. RESULTS: Five cases
of NL were seen during the duration of the study. The preliminary clinical
diagnosis ranged from sarcoidosis to tinea incognito. The commonest clinical
presentation in the Indian scenario was of asymptomatic erythematous to skin
colored plaques and nodules on the shins with or without central atrophy. The
most common site of involvement was the shin (3 of 5 patients). NL was associated
with Diabetes mellitus in only two cases, both of whom were male patients. On
histology, various patterns of inflammation were seen including the palisading,
interstitial, and mixed granulomatous infiltrates. One patient had sarcoidal
granulomas in association with an interstitial pattern. Features seen
consistently in all cases include perivascular lymphoplasmacytic infiltrates,
interstitial lymphocytic infiltrates, and fibroplasia. Interstitial mucin
deposition was not observed in any of the biopsies. CONCLUSION: The diagnosis of
NL was missed in most cases due to the rarity of the disease, absence of
concomitant diabetes, and atypical presentations. Histology was a useful tool in
clinching the diagnosis.
PMID- 24350008
TI - Two cases of giant pyogenic granuloma of scalp.
AB - Pyogenic granuloma is a benign vascular tumor of unknown etiology, though
multiple factors play a role in its onset, e.g., trauma, chronic irritation,
drugs etc., It is commonly seen in children and adolescents. Giant pyogenic
granuloma is its atypical variant. We are presenting two cases of giant pyogenic
granuloma, one, in a 28-year-old adult, presenting as a giant fluffy swelling of
scalp and the other in a 11-year-old child, presenting as a giant ulcerated
globular swelling of the scalp.
PMID- 24350009
TI - Dystrophic epidermolysis bullosa associated with non-syndromic hypodontia.
AB - Epidermolysis bullosa (EB) is a genetic disease associated with fragility and
bullous lesions of the skin and mucous membranes. There are various patterns of
inheritance and histopathology. The disease is associated with systemic and oral
manifestations, among which may be dental decay necessitating oral
rehabilitation. The aim of this article is to present the course of the condition
in a child with dystrophic EB and also to report an association between EB,
hypodontia, and supernumerary teeth which has not been reported earlier in
literature.
PMID- 24350010
TI - Benign cephalic histiocytosis.
AB - A one and a half year old girl born of a non-consanguineous marriage presented
with multiple asymptomatic erythematous to hyperpigmented and skin colored
papules on both cheeks slowly increasing in number of 1 year duration. On the
basis of clinical, histopathological, and immunohistochemistry findings, a
diagnosis of benign cephalic histiocytosis was made.
PMID- 24350011
TI - A rare case of onychomycosis in all 10 fingers of an immunocompetent patient.
AB - Onychomycosis, traditionally referred as a non-dermatophytic infection of the
nail, is now used as a general term to denote any fungal nail infection. It is an
important public health problem due to its increasing incidence and has
significant clinical consequences in addition to serving as a reservoir of
infection. We report a case of Onychomycosis in all 10 fingers of an
immunocompetent male with no co-morbid conditions caused by a non-dermatophytic
fungus, Aspergillus niger. To the best of our knowledge, this is the first case
of its kind to be reported.
PMID- 24350012
TI - Perplexing purpura in two females: Rare case of autoerythrocyte sensitization
syndrome.
AB - Autoerythrocyte sensitization syndrome is a psychologically induced painful
bruising condition. Two female, 19 and 30-year-old presented with recurrent
episodes of painful ecchymotic bruising over accessible areas of body. In the
younger female, episodes were since 3 years and were precipitated by stress and
trivial trauma. The elder female presented with similar lesions since 3 months
which were spontaneous in presentation. There were no obvious psychiatric
manifestations in either. Clinically, ecchymotic changes in various stages of
development were seen. Routine hemogram and coagulation profile were normal.
Histopathology showed extravasated erythrocytes, perivascular neutrophils and
fibrinoid deposition. Intradermal injection of autologous whole blood produced a
painful ecchymotic reaction after 2 h similar to the presenting lesions.
Psychiatric evaluation revealed mild mixed depression - anxiety disorder in the
younger female while the latter revealed no abnormalities. The diagnosis of
autoerythrocyte sensitization syndrome was made based on clinical history and
findings, positive autoerythrocyte sensitization test, psychiatric evaluation and
absence of any other clinical or laboratory pathology.
PMID- 24350013
TI - Familial myomatosis cutis et uteri, segmental type 2.
AB - Reed's syndrome or familial myomatosis cutis et uteri, an autosomal dominant
inherited condition with incomplete penetrance, is characterized by multiple
cutaneous and uterine leiomyomas.[1] Uterine leiomyomas usually commence earlier
compared to that in the general population and cutaneous leiomyomas may precede,
follow or occur concurrently. Few patients may have associated renal cell
carcinoma. Herein we report a case of a 50-year-old female with multiple, painful
cutaneous leiomyomas and who had undergone hysterectomy owing to large uterine
fibroids. Her 18-year-old daughter also has uterine fibroids.
PMID- 24350014
TI - Bullous scabies in an adult: A case report with review of literature.
AB - Scabies is an infestation caused by Sarcoptes scabiei, characterized by
polymorphous lesions that may include burrows, papules, nodules, excoriation, and
crusts. Vesicular and bullous lesions are rather rare. Bullous scabies is
regarded as a distinct subtype of scabies, closely resembling bullous pemphigoid.
Here, we report a case of bullous scabies in an adult male and review the
literature.
PMID- 24350015
TI - Lupus pernio without systemic involvement.
AB - Sarcoidosis is a multisystem, granulomatous disease of unknown etiology that can
affect the pulmonary, reticulo-endothelial, skin, gastrointestinal, cardiac,
musculo - skeletal, endocrine or central nervous system. Exclusive cutaneous
involvement is very rare in sarcoidosis. Lupus pernio is a variant of cutaneous
sarcoidosis presenting with erythematous to violaceous nodules and plaques
located symmetrically over the nose, cheeks, ears and digits. We present a case
of lupus pernio which showed rapid improvement with topical steroids and has yet
not developed any systemic involvement even after 6 years of regular follow up.
PMID- 24350016
TI - Post-steroid panniculitis: A rare case report.
AB - Post-steroid panniculitis (PSP) is a rare clinical entity which presents after
rapid withdrawal of high doses of systemic corticosteroids. As few as 20 cases
have been reported in literature till now. Here, we report a case of post-steroid
panniculitis occurring in a 9-year-old boy after rapid tapering and
discontinuation of corticosteroids administered for the treatment of nephrotic
syndrome. He presented with multiple erythematous painful indurated nodules over
the face, arms, forearms, thighs, and legs. Histopathologic examination of the
nodule revealed lobular panniculitis with lymphocytes, neutrophils, and multiple
multinucleated giant cells. It also showed multiple needle-shaped clefts. Based
on history, clinical features, and histopathologic findings, a diagnosis of post
steroid panniculitis was made and the patient was restarted on systemic
corticosteroids. The lesions resolved in 4 weeks. We report this case to
highlight the importance of gradual tapering of corticosteroids.
PMID- 24350017
TI - Inflammatory vitiligo versus hypopigmented mycosis fungoides in a 58-year-old
Indian female.
AB - Vitiligo, particularly the rarer inflammatory variant, may be difficult to
distinguish from hypopigmented mycosis fungoides (MF) clinically. Complicating
the distinction is that when biopsies are taken from the periphery of early
vitiliginous lesions or from lesions with an inflammatory border (inflammatory
vitiligo), a dermal lymphocytic infiltrate, exocytosis, interface dermatitis, and
mild spongiosis may be seen, all resembling the findings seen in hypopigmented
MF. We present a case demonstrating the difficulty in differentiating between
these two diseases and examine some characteristic clinical and histopathological
features of each. Often, a conclusive diagnosis cannot be made, necessitating
close follow-up of the patient and monitoring for progression of their disease
over time.
PMID- 24350018
TI - Dermatomyositis associated with malignancy: A report of 3 cases.
AB - The association between dermatomyositis (DMS) and various types of malignancies
has been reported in several studies, with an estimated frequency of 20-25%. DMS
may precede, accompany or follow the diagnosis of malignancy. In the present
report, we have discussed three cases of dermatomyositis associated with
malignancy. In the first case, DMS preceded the diagnosis of gastric
adenocarcinoma while in the second and third cases, it followed the diagnosis of
ductal carcinoma of the breast and transitional cell carcinoma of the bladder
respectively. In all three patients, cutaneous and musculoskeletal features of
DMS showed very good response to the treatment, irrespective of the course of
malignancy.
PMID- 24350019
TI - Follicular mucinosis.
AB - Follicular mucinosis is an uncommon inflammatory disorder that characteristically
presents as follicular papules and/or indurated plaques. The face, neck, and
scalp are the most frequently affected sites, although lesions may occur on any
site of the body. Histologically, the disorder is characterized by mucin
deposition in the follicular epithelium. The condition is frequently divided into
primary and secondary forms, with the latter form frequently associated with
mycosis fungoides. In this case report, we describe a child with follicular
mucinosis of the back and trunk and discuss the clinical variants,
histopathological pattern, and treatment options.
PMID- 24350020
TI - Disseminated Mycobacterium chelonae infection: Complicating a case of
hidradenitis suppurativa.
AB - Mycobacteium chelonae is a rapidly growing atypical mycobacteria known to be
pathogenic in humans. We report a case of Hidradenitis Suppurativa (HS) with
diabetes complicated by infection of the lesions with Staphylococcus aureus and
M. chelonae leading to non-healing and discharging lesions. HS is a rare,
insidious and debilitating disease characterized by swollen, painful, inflamed
lesions in the axillae, groin, and other parts of the body that contain apocrine
glands. Discharge from HS lesions are often found to be sterile, however,
polymicrobial bacterial colonization commonly occurs within sinus tracts which
can lead to offensive smelling discharge, infection, cellulitis, and
superinfection. The incidence of HS is very low and the association with M.
chelonae makes it a rare and interesting case.
PMID- 24350021
TI - Erythrokeratodermia variabilis: Two case reports.
AB - Erythrokeratodermia variabilis (EKV) is a rare heterogeneous skin disorder. The
classical EKV first described by Mendes da Costa is characterized by two types of
skin lesions: (1) figurate hyperkeratotic plaques, and (2) transient erythematous
areas. Herein, we report two patients presenting with erythematous and
hyperkeratotic lesions that were histopathologically diagnosed with EKV.
PMID- 24350022
TI - Amyloidosis cutis dyschromica.
AB - Amyloidosis cutis dyschromica is a very rare form of primary cutaneous
amyloidosis characterized by prepubertal onset of hyper and hypopigmented spots
and amyloid deposits in the papillary dermis. We report a case of a 26 year old
female with amyloidosis cutis dyschromica who presented with dyschromic skin
since birth.
PMID- 24350024
TI - Unilateral acrosyringeal lichen planus of palm.
AB - Lichen planus (LP) is a pruritic, benign, papulosquamous, inflammatory dermatosis
of unknown etiology that affects either or all of the skin, mucus membrane, hair
and nail. It presents with varied morphology on the palms and soles. Here we
present a case of unusual acrosyringeal variant of LP on palm. The diagnosis was
confirmed histologically.
PMID- 24350023
TI - Progressive symmetric erythrokeratoderma with nephrotic syndrome: Coincidence or
new association?
AB - Progressive symmetric erythrokeratoderma (PSEK) is a rare genodermatosis with
variable inheritance. It is characterized by symmetrical, erythematous, and
hyperkeratotic plaques on the extremities. We report a case of a 15-year-old boy
with PSEK of autosomal recessive inheritance associated with nephrotic syndrome.
PMID- 24350025
TI - Dermpath quiz.
PMID- 24350026
TI - Interest in leprosy is alive among young dermatologists: An account of IADVL CME
and workshop on leprosy held in Hyderabad, India.
PMID- 24350027
TI - Synopsis of Diet in Dermatology: A one day CME conducted by the Department of
Dermatology, Kasturba Medical College, Manipal, March 3, 2013.
AB - Food is intricately related to mind and body and is one of the elements
sustaining life, in disease as well as in health. There are many myths and
misgivings regarding partake of food and its medicinal properties. The Department
of Dermatology, Kasturba Medical College (KMC), Manipal organized a continuing
medical education (CME) on Diet in Dermatology on 3(rd) March 2013 focusing on
pertinent issues regarding diet and medicinal use of food.
PMID- 24350028
TI - Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell
carcinoma.
AB - Incidence of basal cell carcinoma (BCC), the most common skin cancer in humans,
is rising. Surgery is the mainstay of treatment but there is no standard of care
for locally advanced or metastatic disease. Hedgehog signaling proteins are
critical for cell growth and differentiation during embryogenesis; Hh pathway is
silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in
the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of
smoothened inhibitors such as vismodegib. Food and drug administration approved
this oral, once-daily medication in 2012 to treat adults with metastatic BCC or
locally advanced, recurrent BCC after surgery and also for patients with locally
advanced BCC who are not candidates for surgery or radiation treatment. Clinical
studies have shown it to be highly efficacious and the most common adverse
effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic
modifiers, exemplified by Hh directed therapeutics offer a new hope to patients
with high-surgical morbidity or inoperable tumors.
PMID- 24350029
TI - Zosteriform herpes simplex and herpes zoster: A clinical clue.
PMID- 24350030
TI - A cases series of Piezogenic pedal papules.
PMID- 24350031
TI - Chromoblastomycosis: Report of two cases on face from urban industrial area.
PMID- 24350032
TI - SkIndia Quiz 11 Pigmented plaque on abdomen.
PMID- 24350033
TI - Nevus lipomatosus cutaneous superficialis.
PMID- 24350034
TI - Kyrle's disease.
PMID- 24350035
TI - Nasal dermoid sinus cyst in a young female.
PMID- 24350036
TI - Cavamax W7 composite psoralen ethosomal gel versus cavamax W7 psoralen solid
complex gel for topical delivery: A comparative evaluation.
AB - AIM: The present research work was aimed to formulate and characterize psoralen
encapsulated cavamax W7 composite ethosomal gel and compare its in vitro and ex
vivo behavior against psoralen-cavamax W7-complex reference gel. MATERIALS AND
METHODS: A total of nine formulations of composite ethosomes were prepared by
injection method using 3(2) factorial design and entrapment efficiency was
designated as dependent variable. Concomitantly, psoralen was complexed with
cavamax W7 (1:1 molar ratio) by kneading method and formation of complex was
confirmed by Diffuse reflectance spectroscopy (DRS), scanning electron microscopy
(SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC).
RESULTS: F9 with vesicle size of 183 +/- 2.8 nm, and highest % entrapment
efficiency of 98.12 +/- 1.15 was selected as optimized formulation. Transmission
electron microscopy (TEM) revealed uniform and spherical shaped vesicles. The
optimized formulation F9 was formulated as carbapol gel and compared against
ethosomal gel, psoralen gel, and psoralen cavamax W7 complex gel. The gels were
evaluated for permeation characteristics and the rank order was composite
ethosomal gel > ethosomal gel > psoralen-cavamax W7 complex gel > psoralen gel.
The ethosomal gel (G5) with highest in vitro permeation of 82.48 +/- 2.23% was
subjected to in vivo Confocal laser scanning microscopy (CLSM) studies using
rhodamine B as tracer. The penetration of rhodamine B was uniform, deeper, and
two times faster into epidermis than control gel. CONCLUSION: Conclusively,
cavamax W7 composite ethosomes present themselves as efficient carrier for
superior topical delivery of psoralen and have potential for clinical
applications in minimizing side effects associated with photosensitivity of
psoralen.
PMID- 24350037
TI - Formulation, characterization, in vitro, in vivo, and histopathological
evaluation of transdermal drug delivery containing norfloxacin and Curcuma longa.
AB - OBJECTIVE: In an attempt for better treatment of bacterial infections and burn
wounds, semisolid formulations containing norfloxacin (NF) and natural wound
healing agent Curcuma longa were prepared. The rationale behind employing
combination of NF and Curcuma longa is to obtain synergistic wound healing
effect. The prepared formulations were compared with silver sulfadiazine cream
1%, USP. MATERIALS AND METHODS: Various ointments containing NF and C. longa were
prepared using standard procedures. These formulations were evaluated for
antimicrobial activity against various strains of aerobic and anaerobic
microorganisms. The wound healing property was evaluated by histopathological
examination and by measuring the wound contraction. RESULTS: The significant
antimicrobial and wound healing effects were demonstrated by formulations which
are comparable with silver sulfadiazine 1% cream (P < 0.05). Various
morphological changes were observed by histopathology during the study period
(days 1, 4, 8, and 12) which also supported the wound healing process.
CONCLUSION: Based on the observed antimicrobial and wound healing effects, the
formulations containing combination of NF and Curcuma longa could be employed as
an alternative to commercial silver sulfadiazine 1% cream. This innovative mode
of formulation can be employed for making burn wound healing process more
effective.
PMID- 24350038
TI - Teucrium polium L. extract adsorbed on zinc oxide nanoparticles as a fortified
sunscreen.
AB - INTRODUCTION: Zinc oxide nanoparticles (ZnOn) have been used as carriers and sun
protecting agents for Teucrium polium L. extract to enhance sun protection. ZnOn
was synthesized by hydrolyzing zinc acetate using sodium hydroxide with mean
particle diameter less than 500 nm. MATERIALS AND METHODS: Top flowerings of T.
polium L. were extracted by percolation method with petroleum ether, chloroform,
and 80% methanol consecutively. Methanolic extract was lyophilized and used as a
flavonoid-rich fraction. Sunscreen was prepared by the reconstitution of 0.5 g of
the lyophilized extract in water and mixing with 0.5 to 2 g zinc-oxide (ZnO). Sun
protection factor (SPF) of the aqueous extract of T. polium, the prepared gel, as
well as the zinc oxide suspension alone and in combination with each other was
determined spectrophotometrically based on a modified Transpore((r)) tape method.
RESULTS AND CONCLUSION: Obtained results showed that the T. polium extract has a
wide band of ultraviolet radiation (UV) spectrum absorption ranging from 250 nm
to 380 nm. SPF of the combination product in the ultraviolet B (UVB) area was
greater than 80, revealing a synergistic action between ZnO and T. polium. The
adsorption of flavonoids of T. polium on Zinc-oxide nanoparticles (ZnOn) slowed
down their release thereby lengthening their persistence on the skin and
contributing to further duration of action.
PMID- 24350039
TI - Zinc cross-linked hydroxamated alginates for pulsed drug release.
AB - INTRODUCTION: Alginates can be tailored chemically to improve solubility,
physicochemical, and biological properties and its complexation with metal ion is
useful for controlling the drug release. MATERIALS AND METHODS: Synthesized N,O
dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were
subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate
was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential
scanning calorimetry (DSC). RESULTS: The synthesized polymeric material exhibited
reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives
demonstrated pulsed release where change in pH of the dissolution medium
stimulated the atenolol release. CONCLUSION: Atenolol loaded Zn cross-linked
polymeric beads demonstrated the sustained the plasma drug levels with increased
half-life. Although the synthesized derivatives greatly altered the aqueous
solubility of sodium alginate, no significant differences in in vitro and in vivo
atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl
hydroxylamine derivatives of sodium alginate were observed.
PMID- 24350040
TI - Formulation and evaluation of sustained release enteric-coated pellets of
budesonide for intestinal delivery.
AB - INTRODUCTION: The aim of present work was to develop intestinal-targeted pellets
of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative
colitis and Crohn's disease by extrusion and spheronization method. Current
available oral formulations of Budesonide have low efficacy because of the
premature drug release in the upper part of the gastrointestinal tract. In this
study, a pH-controlled intestinal-targeted pellet of budesonide was established
using 3(2) full factorial design by giving an enteric coating with Eudragit S100.
MATERIALS AND METHODS: Budesonide-sustained release pellets were prepared by
extruder and spheronization technique using a combination of water-soluble and
permeable polymers by applying 3(2) full factorial design. The pellets were
coated by spray coating technique using Eudragit S100 as an enteric polymer. The
pellets were characterized for its flowability, sphericity, friability, and in
vitro drug release. Release behaviour was studied in different pH media. The
release profile was studied for the mechanism of drug release. RESULT: The
optimized formulation showed negligible drug release in the stomach followed by
release for 12 h in the intestinal pH. Differential scanning calorimetry and
Fourier Transform Infrared Spectroscopy studies indicated no interaction between
drug and polymer. Scanning Electron Microscopy image of coated pellets suggested
a uniform and smooth coat over the surface of pellets. Accelerated stability
studies showed a stable nature of drug in the formulation. All evaluation
parameter showed that pellets were good in spherocity and flowability.
CONCLUSION: Sustained release pellets of Budesonide could be prepared by
extrusion and spheronization which released the drug in intestinal pH for an
intestine to treat inflammatory bowel disease. A ratio of polymer combination
could be decided using a full factorial design.
PMID- 24350041
TI - In vitro and in vivo assessment of piroxicam incorporated Aloe vera transgel.
AB - BACKGROUND: The aim of the study was to develop piroxicam-Aloe vera gel (PAG)
formulation and make a pharmacodynamic evaluation of the formulation. MATERIALS
AND METHODS: The gel was prepared by using carbopol 934 as gelling agent and
methyl paraben as a preservative in an Aloe vera gel base. The formulated gel was
also evaluated for physicochemical parameters like pH, viscosity, drug content,
and in vitro diffusion assessment. Pharmacodynamic activity of the formulation
was evaluated in Wistar albino rats. The formulated gel was compared with that of
similar marketed gel (commercial piroxicam gel (CPG)) against the same
parameters. RESULTS: From in vitro studies, an effective drug release from PAG
was observed to be 68.17% when compared with that of the CPG (62.71%) at 180 min
indicating better drug release from the gel formulated in this study. Percentage
inhibition of edema was greater for the preparation of PAG (29.57 mean percent
inhibition after 60 min) compared to marketed gel which exhibited 18.3% after 60
min. CONCLUSION: It was concluded from the results that the Aloe vera gel acts as
an effective gel base to prepare piroxicam gel with high drug loading capacity
and improved anti-inflammatory effect. From the statistical analysis the
formulation of PAG showed better release than the CPG at p < 0.05 level of
significance.
PMID- 24350042
TI - Development and evaluation of 6-mercaptopurine and metoclopramide polypill
formulation for oral administration: In-vitro and ex vivo studies.
AB - INTRODUCTION: The present investigation was to develop a polypill of 6
mercaptopurine and metoclopramide. A polypill with delayed release granules of an
anticancer and immediate release mucoadhesive tablet of antiemetic may result in
the reduction of emesis caused by oral chemotherapy. MATERIALS AND METHODS: 6
Mercaptopurine granules were prepared by wet granulation process. Chitosan,
hydroxypropyl methylcellulose, and ethylcellulose were used as individually as
delayed release polymers. Seven granule formulations (F1-F7) were prepared and
evaluated for flow properties and drug content. Immediate release mucoadhesive
tablets of metoclopramide were prepared by direct compression technique using
pectin and PVPK-40 as mucoadhesive polymers. Three formulations of pectin (L1-L3)
and three formulations of PVPK40 (M1-M3) were prepared using lactose, magnesium
stearate, and mannitol and talc as diluent and glidant, respectively. Tablets
were evaluated for weight variation, hardness, friability, drug content, ex vivo
mucoadhesion time, and in vitro dissolution studies. RESULTS: Formulation F2, F4,
F5, and F7 showed maximum drug content. Formulation F7 exhibited the drug release
up to 2 h and was selected as the best delayed release formulation. All
formulations of metoclopramide showed good drug content ranging from 97.6 % to
100.6%. Formulation M2 among tablets prepared with PVP exhibited desired
mucoadhesion time of 15.33 min which prolongs the duration of drug release in
gastric pouch of the male Wistar rats. Both the selected formulations F7 and M2
were filled into body of capsule size 0 and capsule was evaluated for
technological properties. CONCLUSION: It may be concluded that polypill released
the metoclopramide immediately prior to 6-mercaptopurine.
PMID- 24350044
TI - SPER 3(rd) Annual Conference: 8 March 2014 at Lovely Professional University
(LPU), Punjab, India.
PMID- 24350043
TI - Evaluation of in vivo efficacy and toxicity of prednisolone-loaded hydrogel-based
drug delivery device.
AB - Drugs prescribed for the treatment of moderate to severe inflammatory bowel
disease (IBD) are associated with number of side effects. Targeted drug delivery
is essential for the treatment of inflammatory bowel disease in order to increase
efficacy and reduce toxicity. The established delivery system is designed on
enzyme and time-based release of poorly soluble prednisolone, a drug of choice
for the treatment of moderate to severe inflammatory bowel disease. Their
pharmacological evaluation was done in 2,4,6-trinitrobenzene sulphonic acid
(TNBS)-induced model of colitis in rat. The drug was administered once daily for
3 consecutive days. Visible severity of colitis, tissue to bodyweight ratio,
tissue histology along with nitric oxide (NO), malondialdehyde (MDA) and
myeloperoxidase (MPO) activity of colonic tissue were studied to estimate the
efficacy of the drug-loaded delivery system. The highest efficacy was observed
for formulation in which Eudragit RS100 (EU) was used along with guar gum (GG) in
a ratio 2:5 for the preparation of delivery device. An effective recovery was
observed from the study of tissue histology of animals treated with the drug
loaded optimized formulation and the biochemical parameters supported it. The
toxicity of prednisolone (PD) was reduced significantly as predicted from thymus
to body weight ratio of treated animals. GG and EU RS100 provided a newer
bipolymer combination for the colon-targeted delivery of PD which increased its
efficacy and reduced the toxic side effects. The in vivo experiments presented
effective amelioration from colitis in TNBS-induced animal model of colitis.
PMID- 24350045
TI - Evolution of quality control in pharmaceutical technology.
PMID- 24350046
TI - GHB acid: A rage or reprive.
AB - Gamma-hydroxybutyric acid (GHB) is a naturally occurring analog of gamma
aminobutyric acid (GABA) that has been used in research and clinical medicine for
many years. GHB was used clinically as an anesthetic in the 1960s but was
withdrawn due to side effects that included seizures and coma. GHB has been
implicated in a number of crime types; most notably in drug-facilitated sexual
assault. GHB is abused by three main groups of users: Body builders who use the
substance believing that it stimulated the release of growth hormone; sexual
predators who covertly administer the drug for its sedative and amnesic effects
and club-goers (rave parties) who take the drug for its euphoric effects. The
short-lived hypnotic effects, relative safety and widespread availability of the
drug have made it particularly well suited to this role. The drug has an
addictive potential if used for long term. The primary effects of GHB use are
those of a CNS depressant and therefore range from relaxation, to euphoria,
confusion, amnesia, hallucinations, and coma. Despite the increased regulation,
GHB remains widely available through the Internet where one can easily purchase
the necessary reagents as well as recipes for home production. There are reports
of patients being unresponsive to painful stimuli and cases of oral self
mutilations linked to the abuse of GHB, though quiet rare. Such cases should
remind odontologists that intra-oral lesions may be the result of self-mutilation
either due to mental illness or altered states caused by the use of prescription
or non-prescription drugs.
PMID- 24350047
TI - Interference from ordinarily used solvents in the outcomes of Artemia salina
lethality test.
AB - Methanol, ethanol, Tween 20 and dimethyl sulfoxide (DMSO) are widely used as
dissolving agents in Artemia salina lethality test (aka brine shrimp lethality
test [BSLT]) to screen the pharmaceutical properties of natural products.
Nevertheless, there is lack of toxicity level of these solvents against brine
shrimp. High concentration of these organic solvent might be toxic for this
zoology invertebrate and interfere in the experimental outcomes. To avoid this,
permissible concentration of the solvents used in BSLT was identified. BSLT was
performed to evaluate the toxicity effect of Tween 20, methanol, ethanol and DMSO
at 24 h post-treatment time point against A. salina. The suggested maximum
working concentration (v/v) for DMSO, methanol, ethanol was found to be 1.25% and
that for Tween 20 was 0.16%. LC50 for the solvents were 8.5% (DMSO), 6.4%
(methanol), 3.4% (ethanol) and 2.5% (Tween 20). The findings have shown a
toxicity level among the solvents in descending order as Tween 20 > ethanol >
methanol > DMSO. DMSO is a safer solvent to be used in BSLT compared with other
tested solvents, whereas Tween 20 has been shown to be the most stringent solvent
among the tested solvents. The findings are resourcefully useful to avoid
interference of solvents in the assessment of natural products using BSLT.
PMID- 24350048
TI - Extent of poly-pharmacy, occurrence and associated factors of drug-drug
interaction and potential adverse drug reactions in Gondar Teaching Referral
Hospital, North West Ethiopia.
AB - The aim of this study was to assess the extent of poly-pharmacy, occurrence, and
associated factors for the occurrence of drug-drug interaction (DDI) and
potential adverse drug reaction (ADR) in Gondar University Teaching Referral
Hospital. Institutional-based retrospective cross-sectional study. This study was
conducted on prescriptions of both in and out-patients for a period of 3 months
at Gondar University Hospital. Both bivariate analysis and multivariate logistic
regression were used to identify risk factors for the occurrence of DDI and
possible ADRs. All the statistical calculations were performed using SPSS((r))
software. A total of 12,334 prescriptions were dispensed during the study period
of which, 2,180 prescriptions were containing two or more drugs per prescription.
A total of 21,210 drugs were prescribed and the average number of drugs per
prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and
Minor) were analyzed and DDI were detected in 711 (32.6%) prescriptions. Sex was
not found to be a risk factor for the occurrence of DDI and ADR, while age and
number of medications per prescription were found to be significant risk factors
for the occurrence of DDI and ADR. The mean number of drugs per prescription was
1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar
hospital was able to maintain the limit and prescriptions containing multiple
drugs supposed to be taken systemically. Numbers of drugs per prescription as
well as older age were found to be predisposing factors for the occurrence of DDI
and potential ADRs while sex was not a risk factor.
PMID- 24350049
TI - Efficacy of a classical antiobesity Unani pharmacopial formulation (Safoof-e
Muhazzil) in systolic and diastolic blood pressure: A randomized, open-labeled,
controlled clinical study.
AB - The aim of this study is to evaluate the efficacy of a Unani formulation in
hypertension. A total of 90 patients with total cholesterol level of more than
220 mg/dl with associated conditions were included in this study. A total of 30
patients having a mean systolic blood pressure (BP) of 133.86 mmHg comprising
Group A received Unani formulation Safoof-e-Muhazzil (SM) in its classical powder
form in the dose of 5 g twice a day orally. Group B comprising of 30 patients
with a mean systolic BP of 133.13 mmHg received same drug, but in compressed
tablet form in the same dosage, whereas, 30 patients comprising Group C with a
mean systolic BP of 129.45 mmHg, received Atorvastatin 10 mg as a standard
control. Patients were evaluated on each follow-up at 2(nd), 4(th) and 6(th)
week. The mean systolic BP in Group A and B before treatment was 133.86 +/- 3.028
mmHg and 133.13 +/- 2.852 mmHg, which significantly decreased to 119.33 +/- 1.922
mmHg (P < 0.001) and 119 +/- 1.760 mmHg (P < 0.001) respectively. In the control
Group C before treatment BP was 129.45 +/- 2.499 mmHg and after treatment it
significantly decreased to 124.34 +/- 1.794 mmHg (P < 0.01). The percentage
change after treatment was 10.85%, 10.61% and 3.94% respectively in each group.
Mean diastolic BP in Group A and B before treatment was 85.06 +/- 2.11 mmHg and
84.56 +/- 1.5 mmHg, which significantly decreased to 79.06 +/- 1.56 mmHg (P <
0.001) and 79.96 +/- 1.15 mmHg (P < 0.001) respectively, BP before treatment in
Group C was 83.23 +/- 1.588 mmHg, which was decreased to 124.34 +/- 1.794 mmHg (P
< 0.01). The study results indicate that the test drug was quite effective in
reducing both systolic as well as diastolic BP.
PMID- 24350050
TI - Rationalized design, synthesis and pharmacological screening of amino acid linked
spiro pyrrolidino oxyindole analogs through environment friendly reaction.
AB - INTRODUCTION: The development of newer synthetic approaches toward the synthesis
of polynuclear heteroaromatics and their application in the synthesis of some
biologically active compounds has been discussed in this study. MATERIALS AND
METHODS: The synthesis of novel spiro pyrrolidino oxindoles was performed for the
construction of amino acid linked polynuclear heteroaromatics by cycloaddition
reaction. This reaction method is one of the most important methods for the
construction of spiro pyrrolidino oxindole from the commercially available
starting material isatin. Then the synthesized compounds were subjected for
evaluation of nitric oxide scavenging and cytotoxic effects against tumor cell
lines. RESULTS: All the six synthesized compounds demonstrated promising
antioxidant and cytotoxic effects in vitro. CONCLUSION: Form the present study,
it can be concluded that the synthesized compounds are fruitful in terms of their
chemical purity, structural novelty, marked biological activities (antioxidant
and cytotoxic) in vitro and last of all the lucid and picturesque synthetic
methodology to synthesize the molecules in a in a non-hazardous and environmental
friendly way.
PMID- 24350051
TI - In-vitro alpha amylase and glycosidase inhibitory effect of ethanolic extract of
antiasthmatic drug - Shirishadi.
AB - Asthma and diabetes have strong relationship; both are cause and effect of each
other. Oxidative stress due to bronchial asthma may cause insulin resistance
whereas lack of proper insulin can cause defective smooth muscle relaxant. There
is no single medicine available that can manage both diseases, rather the
mainstay treatment of bronchial asthma causes hyperglycemia. Keeping this problem
in focus, in this study the hypoglycemic effect of an indigenous antiasthmatic
Ayurvedic drug Shirishadi was evaluated. Pancreatic alpha amylase and glucosidase
inhibitors offer an effective strategy to lower the level of post prandial
hyperglycemia via control of starch breakdown. For evaluation of hypoglycemic
activity of drug, in-vitro alpha amylase and alpha glucosidase enzyme inhibition
was calculated. Ethanolic extract of compound showed 76.40% + 0.88% reduction in
alpha amylase activity and 63.85% + 0.36% in alpha glucosidase activity with IC50
0.68 mg/ml and 2.89 mg/ml, respectively. This study suggests that the ethanolic
extract of Shirishadi polyherbal compound effectively acts as alpha amylase and
glucosidase inhibitor leading to a reduction in starch hydrolysis and hence acts
as antiasthmatic as well as hypoglycemic drug.
PMID- 24350052
TI - Effect of formulation factors on in vitro transcorneal permeation of voriconazole
from aqueous drops.
AB - The purpose of this research was to evaluate the effect the formulation factors
on in vitro permeation of voriconazole through freshly isolated goat and sheep
corneas. An increase in the pH of the drops from 4.0 to 8.0 resulted in
significant (P < 0.05) increase drug permeation. Raising concentration of the
drops from 0.05% to 0.2% (w/v) significantly, (P < 0.05) increased drug
permeation, but decreased the percent permeation. Corneal transport of
voriconazole is both pH and concentration dependent. Eye drops containing
disodium edetate (ethylenediaminetetraacetic acid) alone or combination with
benzalkonium chloride showed significantly (P < 0.05) higher permeation as
compared with control formulation. Addition of beta-cyclodextrin to the
formulation enhanced corneal permeation of voriconazole. Compared with control
formulation, voriconazole 0.2% (w/v) drop containing viscosity modifier produced
significant (P < 0.05) decrease in permeation. Most of the formulations showed
higher zone of inhibition against Candida albicans.
PMID- 24350053
TI - Management of knee osteoarthritis with cupping therapy.
AB - The study aimed to evaluate the effect of cupping therapy at a clinical setting
for knee osteoarthritis. A randomized, controlled clinical trial was conducted.
Cupping was performed on 0-6(th) day; 9-11(th) day and 14(th) day, i.e., 11
sittings follow-up to determine longer term carryover of treatment effects
utilizing both objective and subjective assessment. The assessment was performed
before and after treatment spreading over a period of 15 days. The results of
this study shows significant and better results in the overall management of knee
osteoarthritis, particularly in relieving pain, edema, stiffness and disability.
The efficacy of treatment with cupping therapy in relieving signs and symptoms of
knee osteoarthritis is comparable to that of acetaminophen 650 mg thrice a day
orally, in terms of analgesia, anti-inflammatory and resolution of edema with
minimal and temporary side-effects like echymosis and blister formation while as
control drug has greater side-effects particularly on upper gastrointestinal
tract. It is recommended that further studies are conducted with a larger study
samples and of longer duration.
PMID- 24350054
TI - Polypharmacy: The past, present and the future.
PMID- 24350055
TI - Beyond DNA Repair: Additional Functions of PARP-1 in Cancer.
AB - Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that
transfer negatively charged ADP-ribose moieties from cellular nicotinamide
adenine-dinucleotide (NAD(+)) to a variety of protein substrates, altering
protein-protein and protein-DNA interactions. The most studied of these enzymes
is poly(ADP-ribose) polymerase-1 (PARP-1), which is an excellent therapeutic
target in cancer due to its pivotal role in the DNA damage response. Clinical
studies have shown susceptibility to PARP inhibitors in DNA repair defective
cancers with only mild adverse side effects. Interestingly, additional studies
are emerging which demonstrate a role for this therapy in DNA repair proficient
tumors through a variety of mechanisms. In this review, we will discuss
additional functions of PARP-1 - including regulation of inflammatory mediators,
cellular energetics and death pathways, gene transcription, sex hormone- and ERK
mediated signaling, and mitosis - and the role these PARP-1-mediated processes
play in oncogenesis, cancer progression, and the development of therapeutic
resistance. As PARP-1 can act in both a pro- and anti-tumor manner depending on
the context, it is important to consider the global effects of this protein in
determining when, and how, to best use PARP inhibitors in anticancer therapy.
PMID- 24350056
TI - Unveiling stem cell kinetics: prime time for integrating experimental and
computational models.
PMID- 24350058
TI - Rationale for stereotactic body radiation therapy in treating patients with
oligometastatic hormone-naive prostate cancer.
AB - Despite advances in treatment for metastatic prostate cancer, patients eventually
progress to castrate-resistant disease and ultimately succumb to their cancer.
Androgen deprivation therapy (ADT) is the standard treatment for metastatic
prostate cancer and has been shown to improve median time to progression and
median survival time. Research suggests that castrate-resistant clones may be
present early in the disease process prior to the initiation of ADT. These clones
are not susceptible to ADT and may even flourish when androgen-responsive clones
are depleted. Stereotactic body radiation therapy (SBRT) is a safe and
efficacious method of treating clinically localized prostate cancer and
metastases. In patients with a limited number of metastatic sites, SBRT may have
a role in eliminating castrate-resistant clones and possibly delaying progression
to castrate-resistant disease.
PMID- 24350059
TI - Searching for the Achilles Heel of FOXP3.
AB - FOXP3 is a multifaceted transcription factor with a major role in the control of
immune homeostasis mediated by T regulatory cells (Treg). The immunoregulatory
function of FOXP3 may hinder the induction of immune responses against cancer and
infectious agents, and thus, development of inhibitors of its functions might
give new therapeutic opportunities for these diseases. But also, FOXP3 is an
important tumor suppressor factor in some types of cancers, and therefore,
understanding the structure and function of FOXP3 is crucial to gaining insights
into the development of FOXP3-targeted therapeutic strategies. FOXP3 homodimerize
and likely form supramolecular complexes which might include hundreds of proteins
which constitute the FOXP3 interactome. Many of the functions of FOXP3 are
clearly regulated by the interactions with these cofactors contributing
importantly on the establishment of Treg-cell signature. We summarize here the
structural/functional information on this FOXP3 complex, to identify potential
opportunities for the development of new strategies to modulate FOXP3 activity.
PMID- 24350060
TI - Caspase-2 mediates a Brucella abortus RB51-induced hybrid cell death having
features of apoptosis and pyroptosis.
AB - Programmed cell death (PCD) can play a crucial role in tuning the immune response
to microbial infection. Although PCD can occur in different forms, all are
mediated by a family of proteases called caspases. Caspase-2 is the most
conserved caspase, however, its function in cell death is ill-defined. Previously
we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51
induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages.
We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2
mediated and caspase-1-independent proinflammatory cell death in infected
macrophages, which was tentatively coined "caspase-2-mediated pyroptosis".
However, the mechanism of caspase-2-mediated cell death pathway remained unclear.
In this study, we found that caspase-2 mediated proinflammatory cell death of
RB51-infected macrophages and regulated many genes in different PCD pathways. We
show that the activation of proapoptotic caspases-3 and -8 was dependent upon
caspase-2. Caspase-2 regulated mitochondrial cytochrome c release and TNFalpha
production, both of which are known to activate caspase-3 and caspase-8,
respectively. In addition to TNFalpha, RB51-induced caspase-1 and IL-1beta
production was also driven by caspase-2-mediated mitochondrial dysfunction.
Interestingly, pore formation, a phenomenon commonly associated with caspase-1
mediated pyroptosis, occurred; however, unlike its role in S. typhimurium-induced
pyroptosis, pore formation did not contribute to RB51-induced proinflammatory
cell death. Our data suggest that caspase-2 acts as an initiator caspase that
mediates a novel RB51-induced hybrid cell death that simulates but differs from
typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory
pyroptosis. The initiator role of the caspase-2-mediated cell death was also
conserved in cellular stress-induced cell death of macrophages treated with
etoposide, naphthalene, or anti-Fas. Caspase-2 also regulated caspase-3 and -8
activation, as well as cell death in macrophages treated with each of the three
reagents. Taken together, our data has demonstrated that caspase-2 can play an
important role in mediating a proinflammatory response and a hybrid cell death
that demonstrates features of both apoptosis and pyroptosis.
PMID- 24350063
TI - Zinc and copper toxicity in host defense against pathogens: Mycobacterium
tuberculosis as a model example of an emerging paradigm.
PMID- 24350061
TI - Aerosol-induced brucellosis increases TLR-2 expression and increased complexity
in the microanatomy of astroglia in rhesus macaques.
AB - Brucella melitensis, a bacterial pathogen and agent of epizootic abortion causes
multiple pathologies in humans as well as a number of agriculturally important
animal species. Clinical human brucellosis manifests as a non-specific, chronic
debilitating disease characterized by undulant fever, arthropathies,
cardiomyopathies and neurological sequelae. These symptoms can occur acutely for
a few weeks or persist for months to years. Within the brain, endothelial and
glial cells can be infected leading to downstream activation events including
matrix metalloprotease (MMP) and cytokine secretion and Toll-like receptor (TLR)
signaling. These events are likely to lead to tissue remodeling, including
morphologic changes in neuronal and glial cells, which are linked to neurological
complications including depressive behavior, immune activation and memory loss.
Our hypothesis was that B. melitensis infection and neurobrucellosis would lead
to activation of astrocytes through upregulation of TLR2 and stimulate concurrent
changes in the microanatomy. All six animals were infected via inhalation route.
TLR2 expression was approximately doubled in white matter astrocytes of infected
rhesus macaques. There was also a 50% increase in the number of astrocytes per
unit area in subcortical white matter tracts suggesting increased innate immune
activation. This coincided with dramatic increases in the length and complexity
of the cell arbor of hypertrophic astrocytes in both cortical gray and white
matter. Thus, aerosol-induced brucellosis results in dramatically increased
innate immune activation of astrocytes in the absence of widespread
neuroinflammation.
PMID- 24350062
TI - Listeria monocytogenes, a down-to-earth pathogen.
AB - Listeria monocytogenes is the causative agent of the food-borne life threatening
disease listeriosis. This pathogenic bacterium received much attention in the
endeavor of deciphering the cellular mechanisms that underlie the onset of
infection and its ability to adapt to the food processing environment. Although
information is available on the presence of L. monocytogenes in many
environmental niches including soil, water, plants, foodstuff and animals,
understanding the ecology of L. monocytogenes in outdoor environments has
received less attention. Soil is an environmental niche of pivotal importance in
the transmission of this bacterium to plants and animals. Soil composition,
microbial communities and macrofauna are extrinsic edaphic factors that direct
the fate of L. monocytogenes in the soil environment. Moreover, farming practices
may further affect its incidence. The genome of L. monocytogenes presents an
extensive repertoire of genes encoding transport proteins and regulators, a
characteristic of the genome of ubiquitous bacteria. Postgenomic analyses bring
new insights in the process of soil adaptation. In the present paper focussing on
soil, we review these extrinsic and intrinsic factors that drive environmental
adaptation of L. monocytogenes.
PMID- 24350064
TI - Food and water security issues in Russia III: food- and waterborne diseases in
the Russian Arctic, Siberia and the Far East, 2000-2011.
AB - BACKGROUND: The food- and waterborne disease situation in Russia requires special
attention. Poor quality of centralized water supplies and sewage systems,
biological and chemical contamination of drinking water, as well as contamination
of food products, promote widespread infectious diseases, significantly exceeding
nationwide rates in the population living in the two-thirds of Russian northern
territories. OBJECTIVES: The general aim was to assess the levels of food- and
waterborne diseases in selected regions of Russian Arctic, Siberia and the Far
East (for the period 2000-2011), and to compare disease levels among regions and
with national levels in Russia. STUDY DESIGN AND METHODS: This study is the first
comparative assessment of the morbidity in these fields of the population of 18
selected regions of Russian Arctic, Siberia and the Far East, using official
statistical sources. The incidences of infectious and parasitic food- and
waterborne diseases among the general population (including indigenous peoples)
have been analyzed in selected regions (per 100,000 of population, averaged for
2000-2011). RESULTS: Among compulsory registered infectious and parasitic
diseases, there were high rates and widespread incidences in selected regions of
shigellosis, yersiniosis, hepatitis A, tularaemia, giardiasis, enterobiasis,
ascariasis, diphyllobothriasis, opistorchiasis, echinococcosis and
trichinellosis. CONCLUSION: Incidences of infectious and parasitic food- and
waterborne diseases in the general population of selected regions of the Russian
Arctic, Siberia and the Far East (2000-2011) are alarmingly high. Parallel
solutions must be on the agenda, including improvement of sanitary conditions of
cities and settlements in the regions, modernization of the water supply and of
the sewage system. Provision and monitoring of the quality of the drinking water,
a reform of the general healthcare system and the epidemiological surveillance
(including gender-divided statistics), enhancement of laboratory diagnostics and
the introduction of preventive actions are urgently needed.
PMID- 24350057
TI - Mitochondrial dysfunction in cancer.
AB - A mechanistic understanding of how mitochondrial dysfunction contributes to cell
growth and tumorigenesis is emerging beyond Warburg as an area of research that
is under-explored in terms of its significance for clinical management of cancer.
Work discussed in this review focuses less on the Warburg effect and more on
mitochondria and how dysfunctional mitochondria modulate cell cycle, gene
expression, metabolism, cell viability, and other established aspects of cell
growth and stress responses. There is increasing evidence that key oncogenes and
tumor suppressors modulate mitochondrial dynamics through important signaling
pathways and that mitochondrial mass and function vary between tumors and
individuals but the significance of these events for cancer are not fully
appreciated. We explore the interplay between key molecules involved in
mitochondrial fission and fusion and in apoptosis, as well as in mitophagy,
biogenesis, and spatial dynamics of mitochondria and consider how these distinct
mechanisms are coordinated in response to physiological stresses such as hypoxia
and nutrient deprivation. Importantly, we examine how deregulation of these
processes in cancer has knock on effects for cell proliferation and growth. We
define major forms of mitochondrial dysfunction and address the extent to which
the functional consequences of such dysfunction can be determined and exploited
for cancer diagnosis and treatment.
PMID- 24350065
TI - Food and water security issues in Russia II: water security in general population
of Russian Arctic, Siberia and Far East, 2000-2011.
AB - BACKGROUND: Poor state of water supply systems, shortage of water purification
facilities and disinfection systems, low quality of drinking water generally in
Russia and particularly in the regions of the Russian Arctic, Siberia and Far
East have been defined in the literature. However, no standard protocol of water
security assessment has been used in the majority of studies. STUDY DESIGN AND
METHODS: Uniform water security indicators collected from Russian official
statistical sources for the period 2000-2011 were used for comparison for 18
selected regions in the Russian Arctic, Siberia and Far East. The following
indicators of water security were analyzed: water consumption, chemical and
biological contamination of water reservoirs of Categories I and II of water
sources (centralized--underground and surface, and non-centralized) and of
drinking water. RESULTS: Water consumption in selected regions fluctuated from
125 to 340 L/person/day. Centralized water sources (both underground and surface
sources) are highly contaminated by chemicals (up to 40-80%) and biological
agents (up to 55% in some regions), mainly due to surface water sources.
Underground water sources show relatively low levels of biological contamination,
while chemical contamination is high due to additional water contamination during
water treatment and transportation in pipelines. Non-centralized water sources
are highly contaminated (both chemically and biologically) in 32-90% of samples
analyzed. Very high levels of chemical contamination of drinking water (up to
51%) were detected in many regions, mainly in the north-western part of the
Russian Arctic. Biological contamination of drinking water was generally much
lower (2.5-12%) everywhere except Evenki AO (27%), and general and thermotolerant
coliform bacteria predominated in drinking water samples from all regions (up to
17.5 and 12.5%, correspondingly). The presence of other agents was much lower:
Coliphages--0.2-2.7%, Clostridia spores, Giardia cysts, pathogenic bacteria,
Rotavirus--up to 0.8%. Of a total of 56 chemical pollutants analyzed in water
samples from centralized water supply systems, 32 pollutants were found to be in
excess of hygienic limits, with the predominant pollutants being Fe (up to 55%),
Cl (up to 57%), Al (up to 43%) and Mn (up to 45%). CONCLUSION: In 18 selected
regions of the Russian Arctic, Siberia and Far East Category I and II water
reservoirs, water sources (centralized--underground, surface; non-centralized)
and drinking water are highly contaminated by chemical and biological agents.
Full-scale reform of the Russian water industry and water security system is
urgently needed, especially in selected regions.
PMID- 24350066
TI - A review of protective factors and causal mechanisms that enhance the mental
health of Indigenous Circumpolar youth.
AB - OBJECTIVES: To review the protective factors and causal mechanisms which promote
and enhance Indigenous youth mental health in the Circumpolar North. STUDY
DESIGN: A systematic literature review of peer-reviewed English-language research
was conducted to systematically examine the protective factors and causal
mechanisms which promote and enhance Indigenous youth mental health in the
Circumpolar North. METHODS: This review followed the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with elements of a
realist review. From 160 records identified in the initial search of 3 databases,
15 met the inclusion criteria and were retained for full review. Data were
extracted using a codebook to organize and synthesize relevant information from
the articles. RESULTS: More than 40 protective factors at the individual, family,
and community levels were identified as enhancing Indigenous youth mental health.
These included practicing and holding traditional knowledge and skills, the
desire to be useful and to contribute meaningfully to one's community, having
positive role models, and believing in one's self. Broadly, protective factors at
the family and community levels were identified as positively creating and
impacting one's social environment, which interacts with factors at the
individual level to enhance resilience. An emphasis on the roles of cultural and
land-based activities, history, and language, as well as on the importance of
social and family supports, also emerged throughout the literature. More than 40
protective factors at the individual, family, and community levels were
identified as enhancing Indigenous youth mental health. These included practicing
and holding traditional knowledge and skills, the desire to be useful and to
contribute meaningfully to one's community, having positive role models, and
believing in one's self. Broadly, protective factors at the family and community
levels were identified as positively creating and impacting one's social
environment, which interacts with factors at the individual level to enhance
resilience. An emphasis on the roles of cultural and land-based activities,
history, and language, as well as on the importance of social and family
supports, also emerged throughout the literature. CONCLUSIONS: Healthy
communities and families foster and support youth who are resilient to mental
health challenges and able to adapt and cope with multiple stressors, be they
social, economic, or environmental. Creating opportunities and environments where
youth can successfully navigate challenges and enhance their resilience can in
turn contribute to fostering healthy Circumpolar communities. Looking at the role
of new social media in the way youth communicate and interact is one way of
understanding how to create such opportunities. Youth perspectives of mental
health programmes are crucial to developing appropriate mental health support and
meaningful engagement of youth can inform locally appropriate and culturally
relevant mental health resources, programmes and community resilience strategies.
PMID- 24350067
TI - Malignancy and idiopathic inflammatory myopathies.
AB - Association between idiopathic inflammatory myopathies (IIMs) and malignancy is
well known and has been extensively reported in the literature. However, in the
recent years, several new studies were published allowing us to better understand
the clinical characteristics and pathophysiology of cancer-associated IIMs. We
conducted a literature review of cancer-associated IIMs focusing on new data that
was published in the recent years.
PMID- 24350068
TI - Primary prevention of variceal bleeding: pharmacological therapy versus
endoscopic banding.
AB - Variceal bleeding is one of the most feared complications in patients with liver
cirrhosis. It continues to be a leading cause of death among patients with liver
cirrhosis. Although its prognosis has improved over the last several decades, it
still carries substantial mortality. Preventing variceal bleeding has been
extensively studied and evaluated in several studies in the recent years and the
comparison between the different modalities available to prevent variceal
bleeding has been an area of discussion. Currently the two most widely used
modalities to prevent variceal bleeding are pharmacologic (non-selective beta
blockers [NSBB]) and endoscopic (variceal band ligation [VBL]) which have
replaced sclerotherapy in the recent years. In addition to NSBB and recent
carvedilol, different other medications have been evaluated including isosorbide
mononitrates, spironolactone and angiotensin blocking agents. Comparing the
outcomes and adverse effects of these two modalities has been evaluated in
different studies. Some studies have showed superiority of VBL until recently,
when carvedilol has been included, however; overall mortality has been similar in
most trials. Despite that, NSBB remain the first line treatment, as they are
cheaper and relatively effective in preventing both esophageal and gastric
bleeding. The following sections discuss the primary prevention of variceal
bleeding with a focus on NSBB, carvedilol and VBL.
PMID- 24350069
TI - The Effects of beta - Glucan on Fish Immunity.
AB - Administration of glucans through immersion, dietary inclusion or injection has
been found to enhance many types of immune responses, resistance to bacterial and
viral infections and to environmental stress in many fish species. Although the
efficacy of the glucan varies with types and administration, glucan used as an
immunomodulatory and mostly immunostimulatory additive has been found
satisfactory in eliciting immunity in commercial aquaculture. Development of more
efficient administration methods will facilitate the routine and prophylactic use
of glucans as natural immunostimulants of fish. Using a PubMed search, this
review has an extensive literature on glucan in fish immunity.
PMID- 24350070
TI - Onset of Orolingual Angioedema After Treatment of Acute Brain Ischemia with
Alteplase Depends on the Site of Brain Ischemia: A Meta-analysis.
AB - BACKGROUND: Alteplase is used to treat acute ischemic stroke. However, it has
several documented adverse effects, including the development of orolingual
angioedema (OA). Although, OA is a rare side-effect, it is thought to be life
threatening and is difficult to treat. Until date, little is known about this
condition and a better understanding of OA may contribute to improve the
morbidity and mortality amongst patients that develop this condition. MATERIALS
AND METHODS: Using the PubMed and Medknow databases, we searched for peer
reviewed published articles on OA after alteplase administration in 1950-2012. We
gathered demographic data and investigated the relationship between the location
of OA, neurological symptoms and the site of cerebral ischemia. In addition, we
studied the effects of hypertensive premedication on OA development. We
identified 19 published manuscripts that fulfilled our search criteria. These
manuscripts reported 41 cases of OA after alteplase administration. RESULTS: We
found that this condition is associated with cerebral ischemia (P < 0.012) and
that 65.9% (n = 27) of patients who developed OA had a hypertensive drug as a
premedication. CONCLUSIONS: Although OA is a rare side-effect of alteplase, it
can occur depending upon the localization of acute cerebral ischemia.
PMID- 24350071
TI - Clinical predictors of acute kidney injury following snake bite envenomation.
AB - BACKGROUND: Snake bite envenomation is a major public health concern in
developing countries. Acute kidney injury (AKI) is as important cause of
mortality in patients with vasculotoxic snake bite. AIMS: This study was to
evaluate the clinical profile of snake bite patients and to determine the
predictors of developing AKI following snake bite. MATERIALS AND METHODS: Two
hundred and eighty-one patients with snake envenomation were included. Eighty
seven patients developed AKI (Group A) and 194 (Group B) did not. History,
examination findings and investigations results were recorded and compared
between the two groups. RESULTS: In group A, 61 (70.11%) patients were male and
in group B, 117 (60.30%) patients were male. Out of 281 patients, 232 had
cellulitis, 113 had bleeding tendencies, 87 had oliguria, 76 had neuroparalysis,
and 23 had hypotension at presentation. After multivariate analysis, bite to
hospital time (P = 0.016), hypotension (P = 0.000), albuminuria (P = 0.000),
bleeding time (P = 0.000), prothrombin time (P = 0.000), hemoglobin (P = 0.000)
and total bilirubin (P = 0.010) were significant independent predictors of AKI.
CONCLUSIONS: AKI developed in 30.96% of patients with snake bite, leading to
mortality in 39.08% patients. Factors associated with AKI are bite to hospital
time, hypotension, albuminuria, prolonged bleeding time, prolonged prothrombin
time, low hemoglobin and a high total bilirubin.
PMID- 24350072
TI - Tropical pyomyositis.
AB - BACKGROUND: Tropical pyomyositis is characterized by suppuration within skeletal
muscles, manifesting as single or multiple abscesses. Though primarily a disease
of tropics, it is increasingly being reported from temperate regions in
immunosuppressed patients. However, India has only few sporadic case reports.
AIMS: The aim of this study is to evaluate the causative organisms, clinical
presentations, diagnostic modalities, treatment protocols and outcome data in
tropical pyomyositis patients. SUBJECTS AND METHODS: The study was carried out in
Nilratan Sircar Medical College and Hospital, Kolkata over 3 years (July 2010 to
June 2013). A total of 12 patients were diagnosed with tropical pyomyositis
(confirmed with aspiration and culture of pus from muscle). All the investigation
and treatment data were recorded systematically. RESULTS: The presenting feature
was high fever and myalgia in all 12 patients. Quadriceps femoris was the most
commonly involved muscle (50%); followed by iliopsoas (25%). Culture of the
aspirate showed Staphylococcus aureus in nine patients (75%), Klebsiella
pneumonia in one patient (8.33%) and no growth in two patients (16.67%) even
after tubercular and fungal culture. CONCLUSIONS: Tropical pyomyositis can affect
immune-competent individuals. S. aureus is the most commonly cultured organism.
Immediate initiation of appropriate antibiotics and surgical debridement are
required to avoid complications. The prognosis remains excellent if promptly
treated.
PMID- 24350073
TI - Ribosomal protein s6-ps240 is expressed in lesional skin from patients with
autoimmune skin blistering diseases.
AB - BACKGROUND: The in situ signaling transduction within skin biopsies from patients
affected by autoimmune skin blistering diseases is not well-characterized. AIM:
In autoimmune skin blistering diseases, autoantibodies seem to trigger several
intracellular signaling pathways and we investigated the presence of the
phosphorylated form of ribosomal protein S6-pS240 within autoimmune skin
blistering diseases biopsies. MATERIALS AND METHODS: We utilized
immunohistochemistry to evaluate the presence of S6-pS240 in lesional skin
biopsies of patients affected by autoimmune skin blistering diseases including
patients with an endemic and nonendemic pemphigus foliaceus (non EPF), with
bullous pemphigoid (BP), pemphigus vulgaris (PV), dermatitis herpetiformis (DH),
and the respective controls. RESULTS: Most autoimmune bullous skin diseases
biopsies stained positive for S6-pS240 around lesional blisters, including
adjacent areas of the epidermis; and within upper dermal inflammatory
infiltrates, and/or mesenchymal-endothelial cell junctions within the dermis.
CONCLUSIONS: We document that S6-pS240 is expressed in lesional areas of skin
biopsies from patients with autoimmune skin blistering diseases, as well as on
eccrine glands and piloerector muscles. Thus, the role of this molecule in
autoimmune skin blistering diseases warrants further study.
PMID- 24350074
TI - Towards understanding mechanisms of autoimmune bullous skin diseases.
PMID- 24350075
TI - Correlation of severity of coronary artery disease with insulin resistance.
AB - BACKGROUND: Insulin resistance (IR) has known to be associated with coronary
artery disease (CAD), but the assessment of severity of the CAD based on IR in
type 2 diabetes mellitus has not been established in detail. AIMS: The aim of our
study was to establish the correlation between IR and the severity of CAD in type
2 diabetes mellitus. MATERIALS AND METHODS: In a cross-sectional study design, 61
consecutive patients with type 2 diabetes mellitus who underwent coronary
angiogram for the evaluation of CAD were recruited. Fasting blood glucose,
fasting insulin levels, systolic blood pressure and total cholesterol/high
density lipoprotein-cholesterol ratio were determined. Homeostasis model
assessment-IR (HOMA-IR) was correlated with severity of CAD, which was measured
by modified Gensini Score. RESULTS: There was a significant correlation between
log HOMA-IR and severity of CAD (r = 0.303, P = 0.009) in diabetic patients.
Correlation of the Gensini Score with other known risk factors was not
significant. CONCLUSIONS: The results of our study indicate that we might able to
predict the severity of CAD by measure of IR.
PMID- 24350076
TI - Insulin Resistance and Atherosclerosis: Is it Time to Measure HOMA-IR to Predict
Coronary Artery Disease?
PMID- 24350077
TI - Mycobacterium Tuberculosis Infection within a Warthin Tumor: A Case Report and
Literature Review.
AB - CONTEXT: The co-existence of tuberculosis and a Warthin tumor in the parotid
gland is extremely rare. CASE REPORT: A 46-year-old male presented with a mass in
the left parotid region of 6-month duration. The patient's history was only
remarkable for a facial swelling, night sweats and a 38.5 C degrees fever. A 2 *
3-cm mobile, non-tender, mass with a smooth surface was palpated on left parotid
tail. CT examination showed a well-defined 30 mm in diameter tumor mass in the
left superficial lobe of the parotid gland. A superficial parotidectomy was
performed. The final pathological diagnosis of the parotidectomy specimen was
reported as a Warthin tumor and epitheloid granulomas with caseification
necrosis. Purified protein derivative (PPD) was 30 mm in enduration. Two weeks
after the antituberculosis treatment fever declined to normal values and night
sweats decreased. CONCLUSION: Tuberculosis can also be seen in parotid tumors
which can coexist or mimic pleomorphic adenoma, Warthin tumor.
PMID- 24350078
TI - Leaking heart: ticking time bomb!
AB - CONTEXT: Cardiac rupture is a very important but under-recognized complication of
acute myocardial infarction and usually happens within a week of the event.
Sometimes it can be subacute and may not be typical of an acute blow out rupture.
Hence careful evaluation is needed as a missed or delayed diagnosis can be fatal.
An emergent echocardiogram may aid in immediate diagnosis. Surgery is the only
treatment option and is mandatory despite the high mortality risk. CASE REPORT:
An elderly male presented with dizziness and hypotension. Based on the timeline
of his symptomatology, electrocardiographic abnormalities and labs, a subacute
cardiac rupture was suspected in the emergency room itself. A high index of
suspicion is needed to diagnose cardiac rupture. CONCLUSION: Subacute cases can
be missed easily as presentation may not be dramatic. They can rapidly progress
to a blowout rupture increasing mortality risk heavily even with surgical
treatment.
PMID- 24350079
TI - Bilateral putaminal hemorrhages: serious complication of methanol intoxication.
AB - CONTEXT: Methanol intoxication is a life-threatening condition. Hallmark of
clinical presentations include severe wide anion gap metabolic acidosis with very
high serum osmolar gap and visual complication. CASE REPORT: We report a case of
severe methanol intoxication with bilateral putaminal hemorrhage, an uncommon
serious complication. A 56-year-old man presented with altered mental status.
Fundus examination showed optic disc edema. Arterial Blood Gas (ABG) revealed
severe anion gap metabolic acidosis with osmolal gap. Head computed tomography
(CT) showed hypodense lesions in basal ganglia bilaterally. Hemodialysis and
intravenous fomepizole were initiated. Serum methanol level was significantly
elevated. Unfortunately, patient was lethargic 2 weeks after discharge. Repeated
CT of head demonstrated new putaminal hemorrhages. CONCLUSION: Bilateral
putaminal hemorrhage is an uncommon but serious complication in methanol
intoxication. Clinicians should have high index of suspicion for putaminal
hemorrhage when patients with recent methanol intoxication present with altered
mental status.
PMID- 24350080
TI - When to start dialysis in elderly patients.
PMID- 24350081
TI - Testosterone replacement therapy: should it be performed in erectile dysfunction?
AB - The classical etiology of erectile dysfunction (ED) comprises aging and vascular,
neurogenic, psychological and hormonal components. Recent studies have shown that
ED can be the forerunner of serious cardiovascular disturbances. It has also been
reported that peripheral neuropathy and microvascular injuries caused by
pathophysiological changes in patients with diabetes and obesity lead to ED in a
significant number of such cases. These patients develop clinically significant
ED and comprise a significant portion of the patient group which do not respond
to PDE-5 inhibitors. Testosterone has been shown to increase the expression of
PDE-5. This function of testosterone supports its effect on the regulation of
erection and increasing the sexual libido. In view of the complexity of ED, as
well as the effect of testosterone on erection, it is concluded that PDE-5
inhibitors in combination with testosterone replacement would be a better therapy
alternative in the management of erectile dysfunction in hypogonadal patients.
PMID- 24350082
TI - Comparison of vitamin e and L-carnitine, separately or in combination in patients
with intradialytic complications.
AB - BACKGROUND: The most common complications during dialysis are hypotension and
muscle cramps. There are many strategies to prevent and treat these
complications. OBJECTIVES: The aim of this study is to evaluate effects of
vitamin E and L-carnitine supplementation alone and in combination on
intradialytic complications. PATIENTS AND METHODS: In a prospective study, 20
patients with end stage renal disease on chronic hemodialysis that had
intradialytic complications such as hypotension, muscle cramp, nausea, vomiting
and headache were studied. These patients were studied in four 45 day periods,
beginning with no treatment (step 1), receiving vitamin E (200 IU/d) (step 2),
receiving L-carnitine (500 mg/d) (step 3) and their combination (step 4).
Intradialytic complications were recorded in each step and compared between
treatments. RESULTS: All three treatments significantly reduced frequency of
muscle cramps in comparison to baseline values. Vitamin E alone and in
combination with L-carnitine reduced the frequency of muscle cramps more
effectively. Hypotension was significantly lower in combination therapy in
comparison to baseline values and vitamin E treatment. CONCLUSIONS: Vitamin E and
L-carnitine both have comparative effects on intradialytic complications. As the
combination use of vitamin E and L-carnitine could more effectively reduce the
intradialytic complications, it is recommended for daily use in hemodialysis
patients.
PMID- 24350083
TI - Urethral prolapse: contemporary report on a modified ligation over a urethral
catheter treatment approach.
AB - BACKGROUND: Most contemporary series on urethral prolapse report either on the
use of excisional or conservative treatment approaches. OBJECTIVES: To introduce
a modified ligation over a Foley catheter treatment method for urethral prolapse
that addresses most of the previously reported complications. PATIENTS AND
METHODS: Five consecutive patients with urethral prolapse treated between 2003
and 2011, all using the ligation method on an outpatient basis were studied
prospectively. Maintaining the inflated balloon of the Foley catheter with timed
removal of the catheters among other modifications to the original technique is
further described in the article. The main outcome measures were to evaluate for
recurrence, post-operative appearance of the urethral orifice and satisfaction of
parents. Secondarily the actions of the parents of the patients and those of the
receiving physicians were also recorded. RESULTS: The mean age of the patients
was 6 years old (ranging from 3 to 8 years). All parents suspected sexual
molestation and in two cases, the suspected perpetrators were verbally threatened
of dire consequences of their actions if proven. None of the receiving medical
personnel were aware of this condition. Maximum length of catheterization was for
4 days. The post treatment urethral openings appeared normal and there were no
complications. CONCLUSIONS: The ligation method with attention to the
modifications described further in the article is a simple, safe and cost
effective option for the management of urethral prolapse. Maintaining the
inflated balloon of the Foley catheter with timed catheter removal especially
adds predictability to this technique.
PMID- 24350084
TI - Role of multidetector computed tomography for evaluation of living kidney donors.
AB - BACKGROUND: Kidney transplantation from living donors has been increased
recently. Preoperative evaluation of living donor is important to select the
appropriate kidney for transplantation and to decrease donor surgical
complications. OBJECTIVES: The aim of this study was to compare the accuracy of
the use of multidetector computed tomography (MDCT) to evaluate vascular anatomy
in living kidney donors with traditional angiography. PATIENTS AND METHODS: A
total number of 60 living kidney donors who underwent open surgical approach for
transplantation were selected: Kidney anatomy of donors evaluated by CT
angiography (group 1) or traditional angiographic examination (group 2). Renal
vessels anatomy was compared with surgical findings in both groups. RESULTS: The
accuracy for detecting number of main renal arteries were not different in both
groups which were 96.7% in CT angiography group and 90% in traditional
angiography group (P = 0.15). The accuracy for detection of main renal veins were
100% in group 1 and 96.7% in group 2 (P = 0.31). CONCLUSIONS: MDCT has the same
accuracy as traditional angiography to detect renal abnormalities in living
kidney donors.
PMID- 24350085
TI - The evaluation of ureteroscopy and pneumatic lithotripsy results in pregnant
women with urethral calculi.
AB - BACKGROUND: Urinary stone incidence in pregnancy has been reported in a wide
range, from 1 in 200 to 1 in 2000 cases. OBJECTIVES: The aim of this study was to
investigate the efficacy and safety of ureteroscopic treatment and its results
and complications for pregnant women with urinary stones. PATIENTS AND METHODS:
From 2003 till 2011, 113 pregnant patients with symptomatic urolithiasis were
admitted to the urology emergency clinic at Imam Reza hospital. All patients were
initially treated conservatively, resulting in spontaneous passage of the calculi
in 69 patients. Forty-four patients with symptomatic urolithiasis were included
in the study. Post-operative follow ups, including maternal and fetal health was
performed by a gynecologist consult fetal heart rate assessment and urine
analysis and culture and renal and urethral ultrasonography. RESULTS: The mean
age of the patients was 23 years +/- 2 (19-34) and the mean gestational age was
24 +/- 3 weeks. The overall and pneumatic lithotripsy success rate was 100%. All
patients from the interventional group delivered at term with no fetal or
maternal complications. There was no morbidity during and after the operation.
CONCLUSIONS: In conditions, medical management of urinary stones and consequent
renal colic in pregnant women cannot improve patients' symptoms, choosing of a
surgical method like setting of a DJ catheter or URS and pneumatic lithotripsy
can be a safe and effective way for the health of both the mother and fetus. Of
course, more research is needed to establish this approach as the standard method
in pregnancy urinary stones.
PMID- 24350086
TI - Impact of ureteral length on urological complications and patient survival after
kidney transplantation.
AB - BACKGROUND: Urologic complications are of the most important complications after
kidney transplantation which increases mortality and morbidity significantly.
OBJECTIVES: We designed this study to evaluate the association between ureteral
length and postoperative complications. PATIENTS AND METHODS: We recorded the
length of the transplanted ureter during the operation. Ureter-to-bladder
anastomosis was performed using modified Lich-Gregoir method on the ureteral
stent. Complications like urine leakage and increased creatinine were evaluated.
We used both univariate and multivariate analyses and survival analysis according
lengths of ureter. It means that the main variable is ureteral length and other
variables are studied based on it. RESULT: A total of 395 patients with the mean
age of 37 years (range, 18 to 68 years) were enrolled in the study, twenty six
graft lost during the follow-up period. The Mean age of recipients was 37 +/- 13
years. Urinary stenosis was seen in 6 patients (1.5%) and urinary leakage in 4
(1%) patients. The complication rate was not significantly different between
these groups (P = 0.67). We found that there were no significant difference among
complication (P = 0.25), hospitalization (P = 0.31) and survival (P = 0.84) at
5.5 cm length cut off. CONCLUSIONS: The length of transplanted ureter does not
affect the postoperative urologic complications (including urinary fistula and
ureter-to-bladder anastomosis stricture), and it seems that decreased rate of
complication frequency during the recent years is due to technical improvement,
surgeon's skillfulness and development in use of immunosuppressant's
postoperatively.
PMID- 24350087
TI - Effect of oral administration of magnesium on Cisplatin-induced nephrotoxicity in
normal and streptozocin-induced diabetic rats.
AB - BACKGROUND: Cisplatin (CP) therapy as the most common potent chemotherapeutic
process is accompanied by nephrotoxicity. The diabetic state may protect rat
kidney against this toxicity, and magnesium (Mg) on the other hand may reduce the
glucose level in diabetic animals. OBJECTIVES: Current study was planned to
investigate the effect of oral administration of magnesium supplementation on CP
induced nephrotoxicity in normal and Streptozocin (STZ)-induced diabetic rats.
MATERIALS AND METHODS: Male Wistar rats were divided into seven groups and
underwent two experiment protocols. As protocol 1, group 1 was considered as the
sham group. Group 2 (CP group) received CP (2 mg/kg/d) for five consecutive days.
Group 3 (CP + Mg group) received magnesium sulphate (MgSO4, 10 g/L added to the
drinking water) for 10 days and then treated with CP from sixth day. As protocol
2, animals received a single dose of STZ (65 mg/kg i.p.). Three days after
diabetes induction, animals were divided into four groups; Groups 4 (D group), 5
(D + CP group), and 7 (D + Mg + CP group) followed the same manner as groups 1 to
3, respectively; and group 6 (D + Mg group) was treated with MgSO4 alone for 10
days. Finally, blood samples were obtained, and all animals were killed for
kidney tissue investigation. RESULTS: CP administration in normoglycemic rats
significantly elevated the serum levels of blood urea nitrogen (BUN) and
creatinine (Cr) (P < 0.05). However, coadministration of CP and Mg statistically
increased the serum levels of BUN and Cr in both normoglycemic and diabetic
animals when compared to the rats treated with CP alone (P < 0.05), while the
serum level of Mg was significantly increased in nondiabetic groups (P < 0.05).
No significant changes were observed in serum and kidney levels of nitrite; as
well as the testis weight between all normoglycemic groups, whereas Mg decreased
kidney levels of nitrite in diabetic groups when accompanied by CP (P < 0.05).
The kidney and serum levels of malondialdehyde (MDA) enhanced significantly in
nondiabetic rats treated with Mg and CP (P < 0.05). Kidney tissue damage score
(KTDS), kidney weight, and body weight loss were significantly different among
normoglycemic groups (P < 0.05), and Mg promoted the KTDS in diabetic animals
treated with CP. CONCLUSIONS: Oral Mg supplementation did not protect the CP
induced nephrotoxicity in diabetic rats.
PMID- 24350089
TI - Different aspects of fatigue experienced by patients receiving maintenance
dialysis in hemodialysis units.
AB - BACKGROUND: Fatigue, a common symptom reported by patients receiving dialysis, is
a multidimensional and subjective experience which is readily understood by
individuals but difficult to measure. OBJECTIVES: This study was performed to
identify the prevalence of differential aspects of fatigue among patients
receiving maintenance dialysis. PATIENTS AND METHODS: The cross-sectional study
was conducted in two hemodialysis wards in Tehran with a sample of 163
participants. In this study, the multidimensional fatigue inventory was used to
determine the level of fatigue. Demographic data were also collected with self
report survey. To analyze data with SPSS statistical software, test Chi square, T
test, and ANOVA were used. P- Value less than 0.05 was considered significant.
RESULTS: All the patients experienced degrees of fatigue and 50 (30.7%) of the
participants experienced a high level of fatigue. Fatigue scores arrangement was
founded for physical fatigue followed by reduced activity and general fatigue.
Lower levels of fatigue were reported for mental fatigue and reduced motivation.
There was no diversity in this study in the levels of fatigue in respects of
gender and marital status and employment status. Participants with diabetic
nephropathy were the most fatigued. CONCLUSIONS: People with chronic kidney
disease regardless of their age, gender, state of health, and duration of
hemodialysis experience high levels of fatigue; it is particularly important for
health providers to understand this level of fatigue which affects the daily life
of patients.
PMID- 24350088
TI - Coupled Plasma Filtration and Adsorption (CPFA): A Single Center Experience.
AB - BACKGROUND: Coupled plasma filtration adsorption (CPFA) is a novel extracorporeal
blood purification therapy for sepsis which adsorbs both proinflammatory and anti
inflammatory mediators from filtered plasma, thereby achieving early haemodynamic
stability and a reduction in inotropic support requirement. OBJECTIVES: The main
objective was to review our centers' experience with CPFA in septic patients.
PATIENTS AND METHODS: A retrospective chart review of all septic patients who
received CPFA was performed. All patients were initially treated according to the
'surviving sepsis care bundle' with fluid resuscitation, antibiotics, and
inotropes as required. CPFA was started as soon as possible after a
nephrologists' assessment. RESULTS: Twenty five patients with sepsis received
CPFA (15 M, 10 F, mean age 49.60 +/- 18.97 years). Comorbidities included
hypertension (n = 10, 40%), diabetes mellitus (n = 6, 24%), ischemic heart
disease (n = 6, 24%), and an immunosuppressed state (n = 10, 40%). All patients
received one cycle of CPFA with median duration of 5 (1-10) hours. CPFA was well
tolerated but we encountered technical problems, especially filter clotting as
CPFA was performed heparin free. 14 (56%) patients died within 28 days of
treatment. CRP correlated with PCT (P = 0.040) and had an inverse trend with
albumin (P = 0.066). Serum albumin was a strong predictor of mortality.
CONCLUSIONS: The high prevalence of fungaemia and mortality could be attributed
to many patients on chronic immunosuppressive therapy. Nonetheless, CPFA albeit
expensive, does add to our armamentarium of extracorporeal treatment for severe
sepsis. Regional citrate anticoagulation with CPFA may overcome problems with
filter clotting.
PMID- 24350090
TI - Health-related quality of life in hemodialysis patients: an Iranian multi-center
study.
AB - BACKGROUND: The effectiveness of health care and health policy developments are
often determined by health-related quality of life (HRQOL) assessment.
OBJECTIVES: The objective of this study was to explore the potential
corresponding factors and traditional biomarkers of HRQOL in a large number of
Iranian hemodialysis patients. PATIENTS AND METHODS: A total of 6,930 chronic
hemodialysis (HD) patients enrolled. KDCS-SF version 1.3 questionnaire was used
to assess the health related quality of life (HRQOL). We pooled PCS, MCS and KDCS
scores with random effect model from 19 similar studies performed between 1996
and 2010. RESULTS: The mean age was 54.4 +/- 17.1 years. Mean PCS, MCS and KDCS
scores obtained for the study cohort were 40.79 +/- 20.10, 47.79 +/- 18.31 and
57.97 +/- 11.70, respectively; the total score of SF-36 plus KDCS was 51.12 +/-
13.41 as well. The most common primary known disease was hypertension (31.9%) and
the second etiology was diabetes (25.5%). In multilevel logistic regression, Kt/V
between 1 and 1.2 and PCS, KDCS more than 50 were considered as a significant
reduction in the risk of hospitalization. CONCLUSIONS: This study showed that PCS
and MCS score were slightly more than overall results while KDCS was slightly
less than overall results. In addition, dialysis adequacy with Kt/V between 1 and
1.2 is associated with lower rate of hospitalization.
PMID- 24350091
TI - Comparative study of intravenous iron versus intravenous ascorbic Acid for
treatment of functional iron deficiency in patients under hemodialysis: a
randomized clinical trial.
AB - BACKGROUND: Functional iron deficiency (FID) may cause erythropoietin resistance
in patients under hemodialysis (HD). Since the role of chronic inflammation or
oxidative stress in its pathogenesis is unclear, controversy remains to whether
intravenous iron or intravenous ascorbic acid (an antioxidant) can improve this
anemia due to decreased iron availability. OBJECTIVES: The current study compared
the effect of intravenous iron versus intravenous ascorbic acid in the management
of FID in HD patients. PATIENTS AND METHODS: Forty HD patients with hemoglobin
(Hb) <= 11 g/dL, serum ferritin >= 500 ng/mL and transferrin saturation (TSAT) <=
25% were randomly divided into two groups. 20 patients received 100 mg of
intravenous (IV) iron (group I), and 20 patients received 300 mg of IV ascorbic
acid (group II) postdialysis, twice a week for 5 consecutive weeks. Hb and iron
metabolism indices were measured before the onset of the study and after 12 weeks
following therapy. RESULTS: Twenty one percent of all HD patients, exhibited high
serum ferritin, low TSAT and sufficient data for analysis. Both Group I (n = 20)
and Group II (n = 20) patients showed a significant increase in Hb, serum iron,
and TSAT (P < 0.001). There were no significant differences between both groups
in increasing Hb (P = 0.076), serum iron (P = 0.589), serum ferritin (0.725), and
TSAT (P = 0.887). CONCLUSIONS: This study showed that both IV iron and IV
ascorbic acid can improve FID in HD patients. A larger randomized trial is
warranted to determine the optimal management of FID in HD patients.
PMID- 24350092
TI - Vacuolization, dilatation, hyaline cast, debris or degeneration: which one is the
most correlated item to score the kidney damage pathologically in Cisplatin
induced nephrotoxicity model?
AB - BACKGROUND: Nephrotoxicity is characterized and scored by many parameters such as
vacuolization, dilatation, hyaline cast, debris or degeneration in injured renal
tissue. In this short report, we attempt to find, the most correlated parameters
with kidney tissue pathology damage score (PDS) in Cisplatin-induced
nephrotoxicity. METHOD: A total of 207 normal and toxic rats' kidney tissue
(induced by Cisplatin) were evaluated for toxicity intensity by two methods. In
the first method, the tissue damage was scored from 0 to 4, and in the second
method the percentage of vacuolization, dilatation, hyaline cast, debris or
degeneration were determined. The data was analyzed using stepwise discriminant
function and regression analysis. RESULTS: The variables having the higher
discriminant function coefficient were hyaline cast, dilatation, and
degeneration. The linear regression model and the prediction function to
determine the kidney tissue PDS were generated as below. [Formula: see text].
CONCLUSION: According to this finding it is suggested that presence of hyaline
cast and dilatation, and then degeneration in the sample of toxic renal tissue
are the most important item to score the damage intensity.
PMID- 24350093
TI - Bilateral rectus sheath hematoma in kidney transplant patient: case study and
literature review.
AB - Rectus sheath hematoma usually occurs unilateral but rare cases of bilateral
hematoma have been reported. Herein we report the first case of spontaneous
bilateral Rectus Sheath Hematoma in the kidney transplanted patient.
PMID- 24350094
TI - Vesicourethral reflux in pediatrics with hypermobility syndrome.
AB - SUBJECTIVES: Prevalence of benign joint hypermobility syndrome (BJHMS) without
systemic disease seems to be high in children. Little literature is currently
available related to urinary tract diseases in patients with BJHMS. Here, we
report an association between the urinary tract disease and BJHMS. METHODS: We
conducted a prospective case series study of 62 pediatric patients with
musculoskeletal pain to detect urinary tract diseases in Tehran, Iran from
October 2009 to October 2010. The Brighton criteria score was used to diagnose
BJHMS. The collected data included age, gender, grading of vesicoureteral reflux
(VUR), ultrasonography findings, urodynamic results and biochemical tests.
Voiding cystourethrography was used for detection and grading of VUR. RESULTS:
VUR was observed in 60% of patients with BJHMS. However, sonography was normal in
66.7% of patients. The most common grading of reflux was grade II of VUR (37.5%).
Seventy percent of patients with BJHMS and neurogenic bladder had failure to
thrive. CONCLUSION: Our findings showed an increased frequency of VUR in patients
with BJHMS. We suggest that Infants and children with BJHMS should be screened
for VUR.
PMID- 24350095
TI - Forgotten stents, unforgettable patients.
PMID- 24350096
TI - Mineral and bone disease in black african hemodialysis patients.
PMID- 24350097
TI - Mineral and bone disease in hemodialysis patients.
PMID- 24350098
TI - Racial differences in secondary hyperparathyroidism.
PMID- 24350101
TI - Submental Artery Island Flap in Reconstruction of Hard Palate after wide Surgical
Resection of Verruccous Carcinoma, Two Case Reports.
AB - INTRODUCTION: Reconstruction of intraoral soft tissue defects is important in
restoring function and esthetic. In large defects, there will be demand for
regional pedicle flaps or free flaps. Hard palate separates nasal and oral
cavities. Due to the small surface area between flap and remaining palate after
surgical resections, optimal blood supply of the flaps for hard palate
reconstructions are needed. CASE REPORT: This article demonstrates immediate
reconstruction of two edentulous hemimaxillectomy patients with submental artery
Island flap and brief review of this flap discussed. CONCLUSION: Submental Artery
Island flap is an effective and reliable method for intraoral reconstruction of
large soft tissue defects of oral cavity. Donor site morbidity is low and
remaining scar is inconspicuous. Head and neck surgeons familiar with facial
artery and its branching pattern make this flap an appropriate choice for
clinical practice.
PMID- 24350102
TI - Treatment of trauma victims: consideration of the whole perspective.
PMID- 24350100
TI - Overactive bladder syndrome and the potential role of prostaglandins and
phosphodiesterases: an introduction.
AB - In this paper, a general introduction is given, presenting the overactive bladder
syndrome (OAB) and its impact on the quality of life and economical burden in
patients affected. Moreover, the anatomy, physiology and histology of the lower
urinary tract are discussed, followed by a brief overview on the possible role of
prostaglandin (PG) and phosphodiesterase type 5 (PDE5) in the urinary bladder.
The current literature on the role and distribution of PGE2 and its receptors in
the urinary bladder is discussed. In both animal models and in human studies,
high levels of signaling molecules such as PG and cGMP have been implicated, in
decreased functional bladder capacity and micturition volume, as well as in
increased voiding contraction amplitude. As a consequence, inhibition of
prostanoid production, the use of prostanoid receptor antagonists, or PDE
inhibitors might be a rational way to treat patients with detrusor overactivity.
Similarly, prostanoid receptor agonists, or agents that stimulate their
production, might have a function in treating bladder underactivity.
PMID- 24350103
TI - Vascular injuries: trends in management.
AB - ABSTRACT: Vascular injury presents a great challenge to the emergency resident
because these injuries require urgent intervention to prevent loss of life or
limb. Sometimes serious vascular injury presents with only subtle or occult signs
or symptoms. The patient may present weeks or months after initial injury with
symptoms of vascular insufficiency, embolization, pseudoaneurysm, arteriovenous
fistula etc. Although the majority of vascular injuries are caused by penetrating
trauma from gunshot wounds, stabbing or blast injury, the possibility of vascular
injury needs to be considered in patients presenting with displaced long bone
fractures, crush injury, prolonged immobilization in a fixed position by tight
casts or bandages and various invasive procedures. iatrogenic vascular injuries
constitute about 10% of cases in most series; however the incidence is an
increasing trend because more endovascular procedures such as angioplasty and
cardiac catheterization are being performed routinely. Civilian trauma is more
frequently seen in young males. However, it can occur at any age due to road
accidents, firearms, bomb blasts and diagnostic procedures. Most of the time,
civilian trauma causes less tissue damage. There is an epidemic of vascular
injuries in Kashmir valley because of problems in law and order in the past two
decades. This review deals with the topic in detail.
PMID- 24350104
TI - Efficacy of a rapid response team on reducing the incidence and mortality of
unexpected cardiac arrests.
AB - BACKGROUND: Rapid Response Teams (RRTs) assess patients during early phases of
deterioration to reduce patient morbidity and mortality. OBJECTIVES: This study
aimed to evaluate the ability of earlier medical intervention by a RRT prompted
by clinical instability in patients to reduce the incidence of and mortality from
unexpected cardiac arrest at our hospital. PATIENTS AND METHODS: A nonrandomized,
population-based study before 2008 and after 2010 introduction of the Rapid
Response Teams in a 300 bed private hospital. All patients were admitted to the
hospital in 2008 (n = 25348) and 2010 (n = 28024). RRT (One doctor, one senior
intensive care nurse and one staff nurse) attended to clinically unstable
patients immediately with resuscitation drugs, fluid, and equipment. Response was
activated by the bedside nurse or doctor according to predefined criteria. Main
outcome measures were incidence and outcome of unexpected cardiac arrest.
RESULTS: The incidence of unexpected cardiac arrest was 17 per 1000 hospital
admissions (431 cases) in 2008 (before RRT intervention) and 12.45 per 1000
admissions (349 cases) in 2010 (after intervention), with mortality being 73.23%
(274 patients) and 66.15% (231 patients) respectively. After adjustment for case
mix the intervention was associated with a 19% reduction in the incidence of
unexpected cardiac arrest (odds ratio 0.81, 95% confidence interval 0.65-0.98).
CONCLUSIONS: The RRT was able to detect preventable adverse events and reduce the
mortality and incidence of unexpected cardiac arrests.
PMID- 24350105
TI - Evaluation of dextrose water, black tea and orange juice on histopathologic
recovery of surgery-induced intestinal damage in rabbits.
AB - BACKGROUND: The increase in intestinal permeability following damage to the
intestinal mucosa in any surgical procedure, trauma or fasting is well- known.
OBJECTIVES: Our objective was to experimentally evaluate whether antioxidant
consumption is associated with decreased intestinal damage in intestinal surgical
procedures. MATERIALS AND METHODS: Forty rabbits were used to compare the
pathological changes in the intestine after consumption of dextrose water 5%
(D5W), black tea and orange juice in fasting and in cases with intestine
resection and anastomosis. They were divided in to five groups as shams (GI), NPO
(G II), D5W (GIII), black tea (GIV) and orange juice groups (GV). In GII to GV
group with median laparotomy, a 2 cm segment of jejunum was resected and ends of
the bowel were anastomosed. Postoperatively, animals fasted for five days.
Animals in GII were killed after five days of fasting. On day five case groups
were given free access to drinking D5w (GIII), black tea solution (G IV) and
orange juice (GV) for a further 7 days. On day 8, animals were reoperated and the
repaired segment of intestine was removed. Morphologic data were compared in
groups. RESULTS: There were 8 rabbits in each group. There was a significant
difference in villi lengths in the groups (P = 0.003). GV rabbits had obvious
recovery of the villous architecture. CONCLUSIONS: Orange juice as a source of
vitamin C may be an appropriate liquid for postoperative recovery following
intestinal surgery.
PMID- 24350107
TI - Pain and health-related quality of life in war veterans with bilateral lower limb
amputations.
AB - BACKGROUND: Amputation and pain may have considerable impact on health-related
quality of life. OBJECTIVES: The purpose of this study was to assess the impact
of pain on health-related quality of life in a population of war related
bilateral lower limb amputees. MATERIALS AND METHODS: The Veterans and Martyrs
Affairs Foundation (VMAF) database documented 578 patients with bilateral lower
limb amputation; 335 consented to the study (response rate = 58%). The majority
of participants in the sample were males (96.7%). Types of pain were investigated
using a questionnaire. Health-related quality of life (HRQOL) was investigated
using the sf-36 questionnaire. RESULTS: About two third of amputees reported
phantom pain 66.7% (n = 223) and vertebral column pain 60.9% (n = 204). The most
common type of pain was lumbosacral pain 52.8 % (n = 177) followed by neck 18.2 %
(n = 61) and thoracic pain 9.6% (n = 32). Back pain affected on vitality, social
function, mental health and mental component scale in our cases (P < 0.05). Neck
pain affected all components of health-related quality of life (P < 0.05).
Thoracic pain affected quality of life significantly (P < 0.05). The results
obtained from logistic regression analysis indicated that none of the three
spinal column pains including neck, thoracic and lumbosacral pain resulted in
poor physical or mental component scales. CONCLUSIONS: This study revealed that
bilateral lower limb amputees suffer from different types of pain and poor health
related quality of life. Therefore, the assessment and management of all types of
pain are necessary to improve quality of life in veterans.
PMID- 24350106
TI - Isolated small bowel mesentery injury after steering wheel trauma.
AB - BACKGROUND: Isolated small gut mesentery injury after blunt abdominal trauma from
the steering wheel in road traffic accidents is rare. These are always
challenging to diagnose and pose a diagnostic dilemma. OBJECTIVES: To study the
pattern of small gut mesenteric injury by steering wheel blunt abdominal trauma
in road traffic accidents in patients who had laparotomy. PATIENTS AND METHODS: A
10-year retrospective study was done to study isolated small gut mesentery
injury. RESULTS: All patients who had isolated mesenteric small gut injury were
males. Jejunal mesentery was involved in 13 whereas 4 had ileal mesentery injury.
Tear were longitudinal or transverse. CONCLUSIONS: Isolated small mesentery
injury after blunt abdominal trauma from the steering wheel in road traffic
accidents is rare. Tears are either longitudinal or transverse. Suture repair is
to be done. Delay in reaching hospital or reaching the diagnosis could lead to
morbidity and mortality. Isolated mesenteric injury should be considered in any
patient with blunt abdominal trauma from steering wheel injury with no evidence
of any solid organ injury in unstable patients.
PMID- 24350108
TI - Role of liberal primary fasciotomy in traumatic vascular injury.
AB - BACKGROUND: Vascular injury represents less than 1% of all injuries, but deserves
special attention because of its severe complications. Amputation or retention of
a painful functionless limb is the most untoward result of severe vascular injury
or inadequate treatmet. Thus, vascular injury needs a judicious and
multidimensional approach. OBJECTIVES: This retrospective study was done to asess
the outcome of minor modifications of the methodology of extremity fasciotomy by
making it liberal with respect to incision and definition. MATERIALS AND METHODS:
Out of 55 patients in 2008, 45 patients (Group A) had either no fasciotomy or
limited primary fasciotomy, 10 patients (Group B) had primary liberal fasciotomy.
Another group from 2008 onwards had undergone primary liberal fasciotomy in all
the 45 patients (Group C). RESULTS: In group A, we had 5 amputations and one
death. In group B, there were no amputations or deaths and from group C, we had
one amputation and no deaths. CONCLUSIONS: Blunt and distal traumatic vascular
injury of the extremities and its repair should always combined with primary
liberal fasciotomy, which although increases manageable morbidity, avoids
disability (functional as well as anatomical).
PMID- 24350109
TI - Thoracoscopic Sympathicotomy vs Sympathectomy in Primary Hyperhidrosis.
AB - BACKGROUND: Primary hyperhidrosis (P.H.H.) is characterized by excessive sweating
in certain parts of body. It's estimated prevalence is 0%-6.1% in different
populations. In Asian population its prevalence is around 3%. In 57% of cases,
there is a positive family history. OBJECTIVES: To evaluate and compare the early
and late satisfaction, outcomes and complications of thoracoscopic sympathectomy
and sympathicotomy in the treatment of primary hyperhidrosis. MATERIALS AND
METHODS: From April 2007 to January 2011, we prospectively treated 60 primary
hyperhidrosis patients via thoracoscopic surgery. The first 30 patients underwent
sympathectomy and the next 30 patients underwent sympathicotomy. We evaluated
early and late satisfactions, outcomes and complications on the first visit (5
8days) following surgery and 12 months after surgery, for all patients. RESULTS:
The mean operative time was 66.3 minutes in sympathicotomy group and 110.8
minutes in sympathectomy group (P < 0.001). There were no significant differences
between the two groups in overall early and late satisfaction, gustatory
sweating, pompholyx and post-operative pain. There was comparatively less early
and late compensatory sweating (C.S.), and other adverse influences of C.S. in
the sympathicotomy group. CONCLUSIONS: Because of shorter operative time, less
C.S. and less adverse influence of C.S., sympathicotomy seems a better treatment
for primary hyperhidrosis, compared with sympathectomy.
PMID- 24350110
TI - Carpal tunnel syndrome: the role of occupational factors among 906 workers.
AB - BACKGROUND: Carpal tunnel syndrome (CTS) is common in the industrial setting.
However,there is a controversy about the sole role of occupational ergonomic
hazards in CTS. OBJECTIVES: This study was conducted among assembling workers of
a detergent factory and computer users with the aims of A) determination of CTS
prevalence and B) evaluation of personal risk factors and level of exposure to
occupational risk factors via Quick Exposure Check (QEC). MATERIALS AND METHODS:
In this descriptive cross-sectional study, 906 cases (332 assembling workers and
574 computer workers) were enrolled. CTS was assessed by symptoms on the Katz
hand diagram and physical examination. QEC technique was applied to evaluate
physical exposure to the risk factors. RESULTS: According to this study, the
prevalence of probable CTS was 14% in men and 8.9% in women; the rate of probable
CTS was significantly higher in assembly workers than in computer users (P <
0.001). Mean age and work duration in the probable CTS group was statistically
higher than in non-CTS group. But both groups were in the same range (fewer than
30, P = 0.024, 0.004); BMI in the probable CTS group was slightly lower than in
non CTS group, but BMI in both groups were in the normal range. Wrist ratio > 0.7
correlated with increased risk of probable CTS (P < 0.001) Prevalence of probable
CTS was significantly higher in third and fourth levels of QEC (P < 0.001).
CONCLUSIONS: Although this article had limitations, our findings suggest that the
level of occupational exposure is an indicator of CTS development.
PMID- 24350111
TI - Ibn Sina's (Avicenna) Contributions in the Treatment of Traumatic Injuries.
AB - Modern medicine owes much to the endeavours and contributions made by the
ancients that are unfortunately anonymous or even neglected intentionally today.
This study was done to give attention to "the ancient golden times", as the
author believes it deserves the nomination, to give credit to the manner our
ancient physicians and masters practiced medicine and managed traumas in
particular in a way that remains still unrivalled. Undoubtedly such masters as
Galen of Pergamon, Hippocrates, Paul of Aegina and Avicenna paved the road for
the so-called modern medicine and trauma surgery. Focus of this study is on Ibn
Sina or Avicenna as the westerners call him and his methods in handling traumas
of any kind and with any severity in the eleventh century based on the teachings
handed down to him from the ancients; but he was not a mere imitator. What made
him Avicenna was his genius talent in arranging the puzzles in such a way that
was not even imagined by the others.
PMID- 24350112
TI - Deep femoral artery branch pseudoaneurysm after orthopedic procedure requiring
surgical treatment: a case report.
AB - Pseudoaneurysms (PSA) of deep femoral artery (DFA) have been reported following
penetrating and blunt trauma to the thigh and orthopedic procedures of the
proximal femur. We describe a case of pseudoaneurysm of DFA as a late
complication of limb trauma which was confirmed by exploration in an urgent
surgery. After two operations successful surgical repair was performed.
PMID- 24350113
TI - Necrotizing fasciitis of the upper extremity, case report and review of the
literature.
AB - ABSTRACT: Necrotizing fasciitis is a rare, life-threatening infection most
commonly seen in patients with diabetes mellitus, intravenous drug abuse, and
immunocompromised conditions. The extremities are the primary sites of
involvement in as many as two thirds of the cases. In a significant proportion of
patients, the extremities are involved as a result of trauma, needle puncture or
extravasation of drugs. The infection is usually polymicrobial. Treatment
involves broad-spectrum antibiotics and multiple surgical debridements or
amputation. We present a patient with necrotizing fasciitis of the upper limb and
present our experience with this often lethal condition.
PMID- 24350114
TI - The long and winding road.
PMID- 24350115
TI - Degree of Observance of the WHO Surgical Safety Checklist.
AB - BACKGROUND: One of the most important goals of health care organizations is
measuring and improving the quality of health care and reduction of adverse
events. OBJECTIVES: The aim of this study was to evaluate the degree of
observance of the WHO surgical safety checklist at two hospitals in Tehran.
MATERIALS AND METHODS: During this analytic cross-sectional study the degree of
observance and the effects of the checklist on patient outcomes were studied. The
checklist was implemented at two teaching hospitals in Tehran, Iran. RESULTS: One
hundred patients (40 +/- 15 years, 44 (44%) male and 56 (56%) female) were
enrolled in our study. Determination of patients diagnoses, anesthesia safety
check before anesthesia, patient connection to pulse oximetry, allergic airway
disturbance check and aspiration risk, confirmation of patient identity, location
of surgery and surgical method by surgeon and nurse, correct numbering of
materials by nurse and correct ticketing by nurse were carried out in more than
90% of cases. CONCLUSIONS: In conclusion, our study demonstrated that surgery
team members comply moderately to the WHO surgery safety checklist in Iran.
Iranian health care providers need to show more adherence to some items of the
checklist compared to their previous routine.
PMID- 24350116
TI - Impact of trauma dispatch algorithm software on the rate of missions of emergency
medical services.
AB - BACKGROUND: Trauma still stands atop of the list of emergencies. Transfer of
these patients via Emergency Medical Services (EMS) dispatch is critical with
regard to importance of timing. This aspect has achieved greater importance due
to population increase and telephone triage. OBJECTIVES: We aimed to decrease
unnecessary Emergency Medical Services (EMS) missions via a computer program
designed for an algorithmic approach for trauma care by nurses involved in EMS,
to help them evaluate the case more accurately. We named our program "Trauma
Dispatch Algorithm". MATERIALS AND METHODS: First, the most common chief
complaints regarding traumatic events were chosen from searching all the calls in
December 2008 recorded in Tehran, Iran's EMS center; and then an algorithm
approach was written for them. These algorithms were revised by three
traumatologists and emergency medicine specialists, after their approval the
algorithms were evaluated by EMS dispatch center for their practicality. Finally
all data were turned into computer software. The program was used at the Tehran
EMS center; 100 recorded calls assessed with each system were selected randomly.
They were evaluated by another traumatologist whether it was necessary to send a
team to the site or not. RESULTS: The age average was 26 years in both groups.
The "trauma dispatch algorithm" was significantly effective in reducing the
unnecessary missions of EMS by 16% (from 42% to 26%) (P = 0.005). CONCLUSIONS:
This program was effective in reducing unnecessary missions. We propose the usage
of this system in all EMS centers.
PMID- 24350117
TI - Effect of Ilioinguinal Neurectomy on Chronic Pain following Herniorrhaphy.
AB - BACKGROUND: Inguinal hernia is one of the most common male diseases all over the
world with an incidence rate of 18-24% throughout life. Chronic inguinal pain is
one of the complications that prolong return to work time. OBJECTIVES: The main
aim of this study was to determine the effect of ilioinguinal neurectomy on
postoperative chronic pain (PCP) in patients that underwent open inguinal hernia
repair via the Lichtenstein method. MATERIALS AND METHODS: IN THIS RANDOMISED
CONTROLLED CLINICAL TRIAL, MALE PATIENTS WITH UNILATERAL INGUINAL HERNIA WERE
RANDOMIZED INTO TWO GROUPS: 74 cases in the preserved-nerve group and 66 cases in
the nerve-excised group. The method of herniorrhaphy was the classic Lichtenstein
method. Pain and numbness were evaluated at 1 day, 1 week, 1 month, 6 months and
1 year after surgery via visual analogue scale (VAS) system. We used SPSS ver.16
for analysis. RESULTS: All patients were male with mean age of 39.1 years (with a
range of 18 to 68 years). The follow-up rate was 100% after 1 year. Pain severity
was significantly lower in nerve-excised patients at 1 day, 1week, 1 month and 6
months after surgery; but it was not significant after one year, although overall
pain severity was low. Numbness was significantly higher in excised patients at
all endpoints (1 day, 1month, 3 months, 6 months and one year after surgery).
CONCLUSIONS: Ilioinguinal nerve excision at the time of inguinal hernia repair
decreased post-surgical inguinal pain, and it can be used as a routine method in
herniorrhaphy.
PMID- 24350118
TI - Time of admission, gender and age: challenging factors in emergency renal colic -
a preliminary study.
AB - BACKGROUND: Nephrolithiasis is a relatively common problem and a frequent
Emergency Department (ED) diagnosis in patients who present with acute
flank/abdominal pain. The pain management in these patients is often challenging.
OBJECTIVES: To investigate the most effective dose of morphine with the least
side effects in emergency renal colic patients. MATERIALS AND METHODS: 150 renal
colic patients who experienced a pain level of 4 or greater, based on visual
analog scale (VAS) at admission time were included. Pain was scored on a 100 mm
VAS (0 = no pain, 100 = the worst pain imagined). When patients arrived at ED, a
physician would examine the patients and assessed initial pain score, then filled
a questionnaire according to the patient information. Patients were assigned to
receive 2.5 mg morphine sulfate intravenously. We monitored patients' visual
analog scale (VAS), and adverse events at different time points (every 15
minutes) for 90 minutes. Additional doses of intravenous morphine (2.5 mg) were
administered if the patient still had pain. (Max dose: 10 mg). The cumulative
dose of morphine, defined as the total amount of morphine prescribed to each
patient during the 90 minutes of the study, was recorded. Patients were not
permitted to use any nonsteroidal anti-inflammatory drugs as coadjuvant
analgesics during the study period. Subjects with inadequate pain relief at 90
minutes received rescue morphine and were excluded from the study. The primary
end point in this study was pain relief at 90 minutes, defined as either VAS<40
or decrease of 50% or more as compared to the initial VAS. The secondary
objective was to detect the occurrence of adverse effects at any time points in
ED. RESULTS: The studied patients consisted of 104 men and 46 women with the mean
age of 43 +/-14 years (range, 18 to 75 years). There was no statistically
significant difference between the mean age and gender differences in pain
response. Rescue analgesia at 30 minutes were given in 54.5% receiving morphine.
The average time to painless was 35 minutes. But there were no statistically
significant differences between the mean age and gender differences in pain
response (P > 0.05). Older patients responded sooner to morphine than the young.
Most of the patients had a pain score of 90 -100 (77.3 %) at the beginning that
was reduced to 29.4% during the 30 minutes follow up. During the first hour, we
found that 94.7% of the patients had no pain or significant pain reduction and
only 2.1% of the patients still had pain. CONCLUSIONS: We conclude that there
were no significant differences among the gender, time of admission and side -
effects in renal colic patients in response to morphine.
PMID- 24350119
TI - Early coverage of upper extremity electrical injury wounds.
AB - BACKGROUND: An appropriate and well-timed surgery has great impact on a patient's
treatment and can prevent further damage to partially injured structures which if
untreated will be lost leading to severe disability. In the present study we
report our experience with early coverage of electrically injured upper extremity
vital structures with encouraging results. OBJECTIVES: The aim of this study was
to evaluate the results of early flap coverage (less than two weeks) after
electrical injury in the induced wounds of upper extremity. MATERIALS AND
METHODS: The records of electrically injured patients referred during a 10- year
period to Firuzgar Medical Center were evaluated. After one or two sessions of
debridement, the wounds were covered by distant or pedicled flaps and the results
were evaluated according to the number of surgeries, complications and return to
work time. RESULTS: Thirty patients were registered in this study, mean age at
the time of injury was 26.43 (SD = 10.41) years; 40% of patients had right upper
extremity injury, 23.3% had left and 36.7% had bilateral injury. 43.4% of
patients had no complications, amputation rate was 23.3% and nerve injury was
seen in 13.3% of patients. Mean days of return to work was 132.57 (SD = 64.99).
In 11 patients distant flaps were used, 9 patients with graft only and 7 patients
had a combination of graft and regional flaps.The dominant hand involvement in
electrical injury is very high. CONCLUSIONS: We suggest that the routine
treatment protocols of serial debridement until all the wound acquires a bed of
granulation tissue should be revised, because the vital structures such as
tendons and nerves will have undergone dessication necrosis and a young worker
will be crippled for life. Early coverage of partially injured vital structures
is gaining acceptance and this paper confirms the above mentioned treatment
protocol.
PMID- 24350120
TI - Oral and maxillofacial injuries in civilian recruits during mandatory combat
training at military garrisons: a nationwide survey.
AB - BACKGROUND: There is significant prevalence of physical injuries sustained by
civilian recruits at military training garrisons. Civilian recruits sustain these
injuries mostly during the intensive and rigorous military combat-training
period. OBJECTIVES: We sought to determine the prevalence and causes of oral and
maxillofacial injuries as the first step in reducing and preventing them in
civilian recruits (males aged over18 years) during their 2-year mandatory
military service. MATERIALS AND METHODS: In this 2-year study, we referred to
11major military training garrisons in 8 provinces and collected data from
available medical records of military clinics at each garrison. Injuries
occurring in civilian recruits during the intense 2-month military combat
training period were documented. Data regarding the number of civilian trainees,
percentage of those injured, site where the injury was sustained, type of injury
and its causes, etc. as well as demographic data were collected. RESULTS: The
number of civilians called to military service was 153, 886. The ratio of those
injured was 4419/153,886. The percentage of maxillofacial injuries was 20.4%
(903/4419). The majorities of maxillofacial injuries occurred during the first
month (38%) and were due to nonmilitary (86%) rather than military (14%) causes.
From among the military causes, bullets (66%) were the most common cause of
injury, while falls (73%) were the major cause of nonmilitary injuries.
Mountainous terrain was the main cause of falls (51%). The most common military
incidents which led to injury were related to artillery fire and explosions
(33%). Nasal bone fracture was the most common maxillofacial fracture (49%), and
lacerations were the most common soft tissue injury (54%). Among dental injuries,
tooth fracture was most common (66%). CONCLUSIONS: The large number of general
and maxillofacial injuries in civilian recruits during the 2-month combat
training period at military garrisons is disconcerting. This issue warrants
further research to implement methods for identifying, decreasing, and preventing
injuries in civilians at military-training garrisons.
PMID- 24350121
TI - Epidemiology of burn injuries at a newly established burn care center in rasht.
AB - BACKGROUND: Advances in the care of burn injuries have resulted from the efforts
of regional patient-based specialist teams at burn care centers. OBJECTIVES: We
conducted this study to assess the four-year epidemiology of burn injuries in
Rasht, Iran. MATERIALS AND METHODS: In this cross-sectional study, medical
records of 2274 burn patients, treated at Velayat hospital from January 2007 to
December 2010 in Rasht, Iran, were assessed. Age, sex, level of education,
occupation, severity and degree of burn, burn surface area, burn cause and
outcome of patients were evaluated. RESULTS: In our study the overall mortality
rate was 8.7%; 65.7% of patients were men and 34.3% were women. Mean age of
patients was 31.47 +/- 22.67 years. Mean Total Burn Surface Area (TBSA) was 15.24
+/- 18.4. Lowest TBSA was 0.5% and highest TBSA was 100%. Significant
associations were observed between age (P = 0.0001), place of residence (P =
0.004), level of education (P = 0.0001), unemployment (P = 0.0001), marital
status (P = 0.021), causes of burn (P = 0.0001), TBSA (P = 0.0001) and mortality
rate. In our study, no significant difference was observed between age and sex (P
= 0.071). CONCLUSIONS: Due to high prevalence of burn injuries in Iran,
increasing the level of awareness of the society as well as adhering to safety
procedures both at home and workplace is recommended via implementing effective
national safety policies.
PMID- 24350122
TI - Surgically induced digital distal syndactyly for prevention of digital growth
deformities around the joints: a new technique.
AB - BACKGROUND: Correction of digit deformities at or near the Joints is performed
easily ; however, maintaining the result is often difficult either due to
noncompliance of the patient to wear the postoperative splints or problems
related to unequal growth of bones or normal tissues compared to the scarred or
operated side. OBJECTIVES: The aim of this study was to overcome the above
mentioned problems for which we propose the "Distal d Digit Syndactyly"
technique. MATERIALS AND METHOD: This method is based on the concept of suturing
the distal phalanx of the deformed digit to the normal adjoining finger to help
prevent the recurrence of the anomaly during the child's growth period or the
very important three or four postoperative months of scar maturation in the
adult. After the correction of deformity of the finger or toe, "Distal
Syndactyly" is created by two flaps on the adjoining digits; one base is dorsally
hinged and the other one volar and after elevating the flaps they are sutured
together. During the three postoperative weeks care is taken that this attachment
is not disrupted and after healing a "distal syndactyly" is created which is very
durable and in children it stretches with growth and does not impede the digit's
growth. RESULTS: Eleven patients with congenital and traumatic digit anomalies
were treated. The recurrence of the problem was prevented in 9 patients; in 2
patients with intact Syndactyly the contracture recurred by stretching the
Syndactyly skin. The period of the "Joining" ranged from 6 months to three years
and cosmetic appearance was acceptable to the patient and parents. CONCLUSION:
This technique by joining a deformed digit to a normally growing adjacent digit
prevents the postoperative recurrence of the contracture or growth induced
deviation in the digits of noncompliant patients especially children.
PMID- 24350124
TI - Delayed surgical treatment of distal biceps tendon rupture - a case report.
AB - ABSTRACT: Traumatic rupture of the distal biceps tendon is rare. Conservative
treatment can result in reduced flexion and supination power with reduced
function. This case report emphasizes the need for prompt surgical treatment and
describes the possible complications of delayed surgical intervention.
PMID- 24350123
TI - A simple and light weight external fixator for distraction advancement
manoplasty.
AB - BACKGROUND: With the growing interest in long bone distraction several types of
distractors have been introduced; all have the same principle of an outer
structure which acts like a scaffold and the distracting mechanism is a separate
device which is mounted on this outer structure. OBJECTIVES: We have used a
simple and very light weight external fixator we designed and discuss the results
of distraction and advantages of this device . MATERIALS AND METHODS: We applied
our distractor to treat 14 men and four women, with a mean age of 39 years. There
were three thumbs and 23 fingers; 26 digits (18 patients) lengthened by
distraction callotasis and second stage bone grafting evaluated accordingly.
RESULTS: All patients but one were satisfied with the results and a stable pinch
and grip was obtained. After lengthening, all patients maintained sensation of
the finger pulp, as assessed by the Semes - Weinstein test. CONCLUSIONS: The
superiority of this device for manoplasty lies in its simplicity of construction
in addition to being, lightweight and also eases of application.
PMID- 24350125
TI - Salient points to observe in panfacial fracture management.
PMID- 24350126
TI - The long and winding road (part 2).
PMID- 24350127
TI - Comprehensive Management of Maxillofacial Projectile Injuries at the First
Operation; "Picking up the Pieces".
PMID- 24350128
TI - Deep vein thrombosis following below knee immobilization: the need for
chemoprophylaxis.
AB - BACKGROUND: There is controversy regarding routine prophylaxis for deep vein
thrombosis (DVT) in patients treated via a short leg cast or splint following
lower extremity trauma. OBJECTIVES: The main aim of this study is to evaluate the
incidence of DVT and need for chemoprophylaxis in these patients. MATERIALS AND
METHODS: Patients with ankle sprains or stable foot/ankle fractures were entered
in this cross-sectional study. Serum D-dimer levels were measured 2 weeks
following fixation. If the D-dimer levels were above 0.2 micrograms/ml the test
was considered positive and the patient was referred for Doppler ultrasound
examination (DUE) to confirm or rule out the diagnosis of DVT. Finally, the
incidence of DVT was calculated and the role of predisposing factors was
investigated. RESULTS: There were 95 patients with an average age of 38 +/- 13.7
(77.9% males); 46 patients had at least one risk factor for DVT. The D-dimer test
was positive in 21(22.1%) patients. DVT was confirmed by DUE in 3 patients
(3.1%). The incidence of DVT significantly increased in the presence of 3 or more
risk factors (P = 0.01). CONCLUSIONS: It seems that DVT is not a common
complication of below knee fixation and chemoprophylaxis is not necessary when
the patient has less than 3 predisposing factors. With 3 or more risk factors
chemoprophylaxis and periodic follow-ups must be considered.
PMID- 24350129
TI - Application of removable wrist splint in the management of distal forearm torus
fractures.
AB - BACKGROUND: There is considerable variation in the treatment of distal forearm
torus fractures (DFTF), from soft bandaging to cast immobilization. OBJECTIVES:
The present study aimed to show the result of removable wrist splint (RWS) in the
treatment of these fractures. MATERIALS AND METHODS: One hundred forty two
children aged less than 17 years old with DFTF were studied prospectively. These
patients were randomly treated either by a short arm cast (SAC) or a RWS for
three weeks. Finally the treatment results of the two groups were compared.
RESULTS: There were no significant differences regarding degree of pain,
compliance or complications between RWS and SAC groups. Resource savings can be
made with this approach also patients' and parents' satisfaction can be increased
without compromising patients' care. CONCLUSIONS: RWS can be considered as an
easy and acceptable treatment modality with very low costs and complications in
the management of DFTF.
PMID- 24350130
TI - Mental Health Levels and Incidence of Musculoskeletal Complaints among Speed Boat
Crew Members.
AB - BACKGROUND: The occupational health is an important issue. In some jobs, the
working conditions contribute to musculoskeletal complaints and the overall
health of the individual is compromised. Musculoskeletal complaints have gained
credence in the public as one of the most important problems in the field of
occupational diseases. Physical and mental health of crew members with critical
jobs and stressful environments must be considered as well. OBJECTIVES: This
study performed an assessment on levels of mental health and the correlation with
the frequency of accompanying musculoskeletal complaints (such as neck, back and
knee pain) of crew members of speed boats. MATERIAL AND METHODS: 149 onboard crew
members of speed boats were recruited in a descriptive-correlation study by
nonrandom sampling using conducted GHQ12, NMQ and demographic questionnaires.
RESULTS: Although 63.8% (95 people) had what is conventionally defined as normal
mental health, 36.2% (54 cases) had an inherent mental health condition. Overall,
61.1% (91 cases) suffered from back pain, 60.4% (90 cases) complained of knee
pain, and 40.3% (60 patients) complained of neck pain. The combination of knee
and back pain (48.3%) were the most common complaints whereas the combination of
neck and knee pain (31.5%) were the least frequent; 28.2% complained of pain in
all three areas. Interestingly, there was correlation between the presence of
musculoskeletal complaints and less than optimum mental health. CONCLUSIONS: Due
to the high number of musculoskeletal complaints and the compromised mental
health conditions among one-third of the onboard crew members of speed boats,
attention for maintaining and improving the health of these members must be
considered.
PMID- 24350131
TI - Sonographic Detection of Abdominal Free Fluid: Emergency Residents vs Radiology
Residents.
AB - BACKGROUND: Focused assessment with sonography for trauma (FAST) has become a
part of initial examinations in trauma care at emergency departments (ED).
OBJECTIVES: The goal of the present study was to evaluate the accuracy of FASTs
performed by emergency residents (ER) in detection of abdominal free fluid
following blunt trauma. MATERIALS AND METHODS: In this study, the reports of ERs
performing FASTs on 286 admitted patients following blunt trauma were compared
with those of radiology residents (RR) in relation to presence of abdominal free
fluid. In addition, the reports of the two resident groups were compared with the
final abdominal outcome, based on the results of abdominal computed tomography
(CT) and clinical follow up. RESULTS: The ERs had reported abdominal free fluid
in 20 (6.9%) patients while RRs performing FAST had positive results in 22 (7.6%)
patients. The reports of FASTs revealed significant correlation between the two
resident groups (P < 0.001). ERs performing FASTs had 90% sensitivity and 98.5%
specificity in comparison to RRs sonography reports. Furthermore, ER-performed
FASTs had 96.5% accuracy in relation to final outcome. CONCLUSIONS: Following
training, ED residents can perform FAST with high accuracy and specificity,
similar to RR residents, in patients with blunt abdominal trauma.
PMID- 24350132
TI - Outcomes of pin and plaster versus locking plate in distal radius intraarticular
fractures.
AB - BACKGROUND: Distal radius fractures are among the most prevalent fractures
predictive of probable occurrence of other osteoporotic fractures. They are
treated via a variety of methods, but the best treatment has not been defined
yet. OBJECTIVES: This study was performed to compare the results of open
reduction and internal fixation with locking plates versus the pin and plaster
method. MATERIALS AND METHODS: In this prospective study, 114 patients aged 40 to
60 years with Fernandez type III fracture referring to Imam-Reza and Mehr
hospitals of Mashhad from 2009 to 2011, were selected randomly; after obtaining
informed consent, they were treated with pin and plaster fixation (n = 57) or
internal fixation with the volar locking plate (n = 57). They were compared at
the one year follow up. Demographic features and standard radiographic indices
were recorded and MAYO, DASH and SF - 36 tests were performed. Data was analyzed
by SPSS software version 13, with descriptive indices, Mann-Whitney and Chi
square tests. RESULTS: SF-36 test demonstrated a better general health (P <
0.001), mental health (P = 0.006), physical functioning (P < 0.001), social
functioning (P < 0.001) and energy/fatigue (P < 0.001) in LCP group. However,
pain (P = 0.647) was not significantly different between the groups. Physical
limitation (P < 0.001) and emotional limitation (P < 0.001) were greater in the
pin and plaster group. Also, in the LCP group mean MAYO score (P < 0.001) was
more than pin and plaster group. Mean DASH score was not different between the
groups (P = 0.218). The rate of acceptable results of radiographic indices (P <
0.001), grip strength (P < 0.001) and range of motion in supination-pronation (P
< 0.001) in LCP method were better than the pin and plaster method. CONCLUSIONS:
In treatment of intra-articular distal radius fractures in middle-aged patients
internal fixation with locking plates may be prefered to pin and plaster as the
treatment of choice.
PMID- 24350133
TI - Local erythropoietin injection in tibiofibular fracture healing.
AB - BACKGROUND: Erythropoietin (EPO), in addition to its function as an
erythropoiesis regulator has a regenerative activity on some nonhematopoietic
tissues. Animal studies have suggested a role for erythropoietin in bone healing.
OBJECTIVES: The present study aimed to evaluate the effects of local EPO
injection in healing of tibiofibular fractures. MATERIALS AND METHODS: In a
prospective double blind study, 60 patients with tibiofibular fracture were
divided to equal EPO or placebo groups, randomly. Patients received local
injection of either EPO or a placebo to the site of fracture two weeks after
surgical fixation. Patients were followed by clinical and radiographic
examination to determine the union rate. The period of fracture union and
incidence of nonunion were compared between the two groups. RESULTS: The
demographic data and types of fractures were similar in the both groups. The mean
duration of the fracture union was 2.1 weeks shorter in those treated with EPO (P
= 0.01). Nonunion was observed in 6 patients of the control group and 2 receiving
EPO (P = 0.02). No patient experienced any adverse effect from local EPO
injections. CONCLUSIONS: EPO injection into the site of tibiofibular fractures
may possibly accelerate healing.
PMID- 24350134
TI - Trauma-related Therapeutic Procedures at Shohada Trauma Center in Tabriz.
AB - BACKGROUND: To decrease the burden of injuries it is essential to have an
overview of trauma patterns and its management at regional trauma centers.
OBJECTIVES: The aim of this study was to investigate some patterns of trauma and
trauma-related therapeutic interventions at our trauma center. MATERIALS AND
METHODS: In a cross-sectional study, 19530 trauma cases admitted to the emergency
department and hospital wards of Shohada University Hospital during 2007-2008
were assessed. RESULTS: Of the 19530 trauma cases, 14960(76.7%) were males. Mean
(SD) of age was 31(19.9) years. The elderly aged 65 and above, comprised 10%
(1953) of the participants; while 44 were infants. Falls and traffic injuries
were the most common cause of injuries among trauma patients. Most of the
mortalities were men comprising 74% of the 57 deaths. Reduction of fractures and
dislocations were the most common types of operations among trauma patients.
CONCLUSIONS: Young men form the target group for possible interventions to
decrease the burden of trauma following falls and traffic accidents.
PMID- 24350135
TI - Autologous blood injection for treatment of tennis elbow.
AB - BACKGROUND: Tennis elbow (TE) is a common myotendinosis. It was first described
by Runge in 1873; different modes of treatment are used in management of TE.
OBJECTIVES: This study aimed to report the results of autologous blood injection
(ABI) in the treatment of TE. MATERIALS AND METHODS: A prospective case study was
performed to evaluate the results of ABI in the management of TE. The level of
pain based on Nirschl phase scale (NPS) and a visual analogue scale (VAS) was
calculated before and 1, 3 and 6 months after injection; then satisfaction was
assessed. RESULTS: Twenty-nine patients with diagnosed TE were treated by ABI
(24% males, 76 % female). The mean age of the patients was 44.1 +/- 5.2 years.
The level of pain on VAS decreased from 6.46 +/- 2.08 to 0.54 +/- 0.7 (P=0.001)
and on NPS from 6.15 +/- 1.48 to 0.54 +/- 0.76 (P = 0.001) 6 months after
treatment. At the end of the study, 84% of patients expressed a high level of
satisfaction. CONCLUSIONS: Given the acceptable outcomes, autologous blood
injection can be considered a good treatment option for TE when traditional
treatment has fails.
PMID- 24350136
TI - Open reduction and internal fixation of intraarticular fractures of the humerus:
evaluation of 33 cases.
AB - BACKGROUND: Standard treatment of type C elbow fractures is open reduction and
internal fixation using reconstruction plates and pins. OBJECTIVES: The aim of
this study was to evaluate the functional outcome following internal fixation of
intraarticular fractures of the distal humerus (AO Type C) with a minimum follow
up of three years. A retrospective evaluation was undertaken. PATIENTS AND
METHODS: Thirty-three patients (28 males, 5 females; mean age 34.3years) type C
elbow fractures were treated and observed over a period of three years. Six
fractures were open and 27 closed; causes were falls (7 cases), traffic accidents
(22 cases) and altercation (4 cases). All operations were performed using a
posterior approach with an olecranon osteotomy. Mean duration of follow-up was 18
months (range 6-36). Mean duration of fracture healing was 2.3 months (range 2
4). Functional outcomes were assessed by Jupiter criteria. RESULTS: Excellent
results were found in 69.7% (23 cases), very good reaults and good results were
found in the remaining 30.3% (10 cases). Three of 33 patients 9% (3 cases)
presented postoperative complications. No patient exhibited symptoms of ulnar
nerve injury following surgery. One patient had cubitusvarus deformities and one
case had heterotopic ossification. One patient had malunion and one case had deep
infection. CONCLUSIONS: Complications were minimal and outcomes were satisfactory
in patients with type C distal humerus fractures who underwent bilateral plate
fixation via a posterior approach.
PMID- 24350137
TI - Tendon transfer in hand trauma: a case report.
AB - In this report we describe our encounter of a case of hand trauma referred to our
center presenting with incomplete left thumb amputation at metacarpal level with
extensor pollicis longus (EPL) and flexor pollicis longus (FPL) tendon avulsion
from the tenomuscular junction. After metacarpal bone fixation the ulnar digital
artery was anastomosed and the digital nerves were coapted. Transfer of extensor
indicis proprius (EIP) to EPL and side-to-side suturing of the FPL to the deep
flexor tendon of the index finger were performed.
PMID- 24350138
TI - Non-anatomical surgical solutions for difficult non-unions: case series.
AB - ABSTRACT: Non-union occurs when bone healing ceases and does not continue without
some type of intervention. Classification of non-union is traditionally based on
the amount of callus or bone healing at the fracture site. Successful treatment
of non-union often depends on appropriate reduction and realignment of the
fracture, bone grafting if necessary, and stabilization. This may not be possible
in some neglected and complicated non-unions. Under these circumstances,
modification of the standard techniques or a limited surgical interference, that
might not be anatomical, may succeed in improving function. We present four cases
of non-anatomical salvage solutions for difficult long bone non-unions with
satisfactory functional outcome.
PMID- 24350140
TI - Don'T you just hate peer review?
PMID- 24350139
TI - Posterior hip dislocation associated with posterior wall acetabular fracture and
ipsilateral intertrochantric fracture: a very rare case report.
AB - ABSTRACT: Traumatic hip dislocations are common in high-energy motor vehicle
accidents. We present a case of a 43-year old man who sustained posterior hip
dislocation with posterior wall acetabular fracture and ipsilateral
intertrochantric fracture following a motorcycle accident. Urgent open reduction
and internal fixation of the hip fracture-dislocation and fixation of
intertrochantric fracture with a dynamic hip screw were done. To our knowledge,
such an injury has been rarely reported in the literature. Possible mechanisms of
injury and operative procedures are discussed. Radiographic follow-up after eight
months showed union. No major complications were observed in our patient.
PMID- 24350141
TI - Orthopedic injuries following the East azerbaijan earthquake.
AB - BACKGROUND: Evaluating demographic characteristics, distribution and types of
orthopedic injuries following major earthquakes may be helpful in future planning
for disasters. OBJECTIVES: This study aimed to analyze data from trauma patients
with extremity injury resulting from the earthquakes of East Azerbaijan, Iran.
PATIENTS AND METHODS: Medical records of 686 patients admitted to Shohada
hospital, Trauma Center of Tabriz University of Medical Sciences were reviewed.
There were 200 patients with extremity injury assessed. Demographic
characteristics and patterns of injuries in these patients were evaluated.
RESULTS: In this study, there were 105 females (52.5%) and 95 males (47.5%), out
of which, 6 (3%) patients with associated severe head injuries died. The most
common sites of injury were lower extremities (81 patients, 41.5% of total
victims) while 32 patients (16%) suffered from both upper and lower extremity
injuries. Open Fractures were seen in lower extremities of 26 (13%) patients.
Compartment syndrome was observed in 3 (1.5%) patients with lower limb fractures.
Also, 42 (21%) patients living in Tabriz were injured while they were running
away (falling down the stairs and jumping out of windows). CONCLUSIONS: Extremity
injuries especially open fractures of lower limbs account for the majority of
hospitalized victims. Compartment syndrome is one of the main problems that
should be addressed. Our study demonstrates that people still need more education
regarding earthquakes and the government should direct more attention to this
issue.
PMID- 24350142
TI - Long-term follow-up results of delayed fixation of femoral neck fractures in
adults.
AB - BACKGROUND: Femoral neck fractures are urgent injuries that require precise
reduction and stable fixation. In some cases, however, early treatment is not
possible. OBJECTIVES: The present study aimed to evaluate long-term results of
delayed fixation of femoral neck fractures using cannulated screws. PATIENTS AND
METHODS: This retrospective descriptive-analytical study was conducted on 26
patients with femoral neck fractures. The patients were treated through a closed
reduction and fixation method using cannulated screws. Patients were followed up
for at least five years and the rate of complications was determined. RESULTS: In
this study, 26 patients with mean age of 34.3 years were assessed. Average time
interval from injury to surgery was 46.4 +/- 12.2 hours; 18 patients (69%) were
operated on with more than 36 hours of delay. Incidence of AVN and nonunion was
reported in 10 (38.4%) and 3 (11.5%) patients, respectively. CONCLUSIONS: Time
plays an important role in treatment results of femoral neck fractures. To treat
the fractures, closed reduction and fixation using cannulated screws may still be
the best option.
PMID- 24350143
TI - Delayed presentation of traumatic diaphragmatic hernia: a diagnosis of suspicion
with increased morbidity and mortality.
AB - BACKGROUND: Diaphragmatic rupture due to blunt or penetrating injury may be a
missed diagnosis in an acute setting and can present with a delayed complication
with significantly increased morbidity and mortality. OBJECTIVES: The objective
of this study is to better understand why diaphragmatic tears with delayed
presentation and diagnosis are so often missed and why traumatic diaphragmatic
tears are difficult to diagnose in emergency settings and how they present with
grievous complications. PATIENTS AND METHODS: Eleven patients with diaphragmatic
hernias with delayed presentation and delayed diagnosis were operated within the
last five years. All patients presented with different complications like gut
gangrene or respiratory distress. RESULTS: Out of eleven patients who were
operated on for diaphragmatic hernia, three patients (27%) died. Three patients
required colonic resection, one patient needed gastrectomy and one patient
underwent esophagogastrectomy. CONCLUSIONS: A small diaphragmatic tear due to
blunt trauma to the abdomen is difficult to diagnosis in acute settings due to
ragged margins and possibly no herniated contents and usually present with a
delayed complication. Therefore a careful examination of the entire traumatized
area is the best approach in treating delayed presentation of traumatic
diaphragmatic hernia prior to development of grievous complications.
PMID- 24350144
TI - Mandibular Angle Fractures: Comparison of One Miniplate vs. Two Miniplates.
AB - BACKGROUND: Monocortical miniplate fixation is an accepted and reliable method
for internal fixation of mandibular angle fractures. Although placement of a
second miniplate may theoretically provide more stability; however, the clinical
importance of this issue remains controversial. OBJECTIVES: The present study
assessed the postoperative complications and outcomes associated with the
fixation of mandibular angle fractures using 1 and 2 miniplates in patients with
favorable mandibular angle fractures. PATIENTS AND METHODS: A prospective study
of 87 patients (73 males, 14 females) with favorable mandibular angle fractures
was done. In the first group, a 4-hole miniplate was placed at the superior
border through an intraoral approach. In group 2, patients were treated with 2
miniplates, one placed at the superior border (similar to group 1) and the other
on the lateral aspect of the angle at the inferior border through an intraoral
and transcutaneous approach using a trocar. Postoperative complications including
malocclusion, malunion and sensory disturbances associated with surgery,
additional maxillomandibular fixation (MMF) by means of an arch bar and wires for
a longer period (for delayed union) and infection were assessed in patients of
both groups up to 12 months postoperatively. The data were analyzed using the chi
square test. RESULTS: In the single miniplate group, 25 patients showed lip
numbness associated with surgery (55.6%), 22 patients required additional use of
MMF (48.9%) and 3 patients developed infections (6.7%). In the double miniplate
group 20 patients showed lip numbness associated with surgery (47.6%), 18
patients required additional use of MMF (42.9%) and 1 patient developed infection
(2.4%). None of the patients in either group showed malocclusion or malunion. No
significant difference was observed between the groups regarding overall
complication rate. CONCLUSIONS: In this study, use of one miniplate or two
miniplates for treatment of favorable mandibular angle fractures was associated
with a similar incidence of complications. Thus, it seems that the use of two
miniplates in this setting may not be warranted, nor cost-efficient.
PMID- 24350145
TI - Architecture capabilities to improve healthcare environments.
AB - BACKGROUND: The physical environment of healthcare buildings has great importance
in issues such as patient safety, functional efficiency, user satisfaction,
healthcare outcomes, and energy and resources consumption. OBJECTIVES: The
present study assesses physical environments of Iranian healthcare buildings.
MATERIALS AND METHODS: This study was performed using a descriptive-analytical
method. Data collection was carried out via a written questionnaire. RESULTS:
Based on the findings of this study, "functional efficiency", "user
satisfaction", "environmental issues", "patient safety", "accountability in
incidents and disasters", and "flexibility" are regarded as the most issues in
the country's hospitals. Also, none of the parameters is "without any problem"
and has a "desirable status". CONCLUSIONS: According to the responses, all of the
healthcare buildings in this research had flaws in their physical environment,
which require attention. Thus, it is necessary to review and pay more attention
to the architecture of the country's healthcare buildings.
PMID- 24350146
TI - Surgical management of acetabular fractures: a case series.
AB - INTRODUCTION: For decades, acetabular fractures were treated conservatively.
Judet et al. in 1960s established the operative treatment of these fractures by
continuous improvement of pre-operative evaluation and classification of
fractures. Several studies demonstrated that accurate fracture reduction
decreases the incidence of post-traumatic arthritis and improves functional
outcome. CASE SERIES: We report 67 consecutive patients who underwent surgical
treatment for acetabular fracture; 44 patients were available for follow-up. In
35 (79.5%) cases, congruent reductions were achieved. The final mean Harris hip
score was 81.8 (53-95). Functional outcomes according to Harris score were
excellent and good in 31 patients (70.5%). CONCLUSIONS: The results of internal
fixation of displaced acetabular fractures in our series were satisfactory.
PMID- 24350148
TI - An unusual combination of acetabular and pelvic fracture: is this a new subtype
of acetabular fracture?
AB - INTRODUCTION: Acetabular fractures are a common problem among young males. An
acetabular fracture with disruption of the joint surface, if untreated, will
rapidly lead to post-traumatic osteoarthritis. Proper reduction and internal
fixation depend on accurate classification and the quality of imaging. CASE
PRESENTATION: We present an unusual form of acetabular fracture, which is not
included in the conventional classification (Judet and Letournel) ; this occurred
in a middle-aged male who was operatively treated without any complications. In
this case due to posterior extension of the fracture into the SI joint and
concomitant anterior column fracture in the area above the acetabular dome, no
portion of the acetabular anterior surface remained connected to the innominate
bone. CONCLUSIONS: We recognized this type of fracture and treated it similarly
to both column fractures. We recommend that the classification of acetabular
fractures be modified to include this type of fracture.
PMID- 24350147
TI - Two-stage surgical treatment for non-union of a shortened osteoporotic femur.
AB - INTRODUCTION: We report a case of non-union with severe shortening of the femur
following diaphysectomy for chronic osteomyelitis. CASE PRESENTATION: A boy, aged
16 years presented with a dangling and excessively short left lower limb. He was
using an elbow crutch in his right hand to help him walk. He had a history of
diaphysectomy for chronic osteomyelitis at the age of 9. Examination revealed a
freely mobile non-union of the left femur. The femur was the seat of an 18 cm
shortening and a 4 cm defect at the non-union site; the knee joint was ankylosed
in extension. The tibia and fibula were 10 cm short. Considering the extensive
shortening in the femur and tibia in addition to osteoporosis, he was treated in
two stages. In stage I, the femoral non-union was treated by open reduction,
internal fixation and iliac bone grafting. The patient was then allowed to walk
with full weight bearing in an extension brace for 7 months. In Stage II,
equalization of leg length discrepancy (LLD) was achieved by simultaneous
distraction of the femur and tibia by unilateral frames. At the 6 month follow-
up, he was fully weight bearing without any walking aid, with a heel lift to
compensate the 1.5 cm shortening. Three years later he reported that he was
satisfied with the result of treatment and was leading a normal life as a
university student. CONCLUSIONS: Two-stage treatment succeeded to restore about
20 cm of the femoral shortening in a severely osteoporotic bone. It has also
succeeded in reducing the treatment time of the external fixator.
PMID- 24350150
TI - Ruptured aneurysm of the splenic artery: a rare cause of abdominal pain after
blunt trauma.
AB - INTRODUCTION: Splenic artery aneurysms (SAAs) are rare (0.2-10.4%); however, they
are the most common form of visceral artery aneurysms. Splenic artery aneurysms
are important to identify, because up to 25% of the cases are complicated by
rupture. Post- rupture mortality rate is 25% -70% based on the underlying cause.
Herein we present a young patient with abdominal pain after blunt abdominal
trauma due to rupture of an SAA. CASE PRESENTATION: A 27-year-old male, without a
remarkable medical history, who suffered from abdominal pain for 2 days after
falling was admitted to the emergency department with hypovolemic shock. Upon
performing emergency laparotomy a ruptured splenic artery aneurysm was found.
CONCLUSIONS: It is important to consider rupture of a splenic artery aneurysm in
patients with abdominal pain and hypovolemic shock.
PMID- 24350149
TI - A Rare Case of Gorham's Disease: Primary Ulnar Involvement with Secondary Spread
to the Radius and Elbow.
AB - INTRODUCTION: Gorham's disease is a rare musculoskeletal disease which causes
progressive osteolysis and is characterized by massive bone destruction due to
proliferation of vascular elements along with a great number of osteoclasts. The
etiology of the disease is unknown. Gorham's disease is essentially rare in the
forearm bones. As far as we know, only 2 cases of Gorham's disease of the forearm
have been reported with 1 of them in the radius and the other starting in the
radius and spreading to the lower portion of the humerus. CASE PRESENTATION: This
case report shows that Gorham's disease may affect the ulna primarily and spread
to adjacent bones despite the fact that there are no such reports in the
literature. CONCLUSIONS: Gorham's disease has several manifestations as primary
bone involvement. As in this rare case the ulna may be affected first and then
the disease may spread to adjacent bones. More studies are needed to better
recognize the behavior of this rare disease.
PMID- 24350151
TI - Minding the Prevention Protocol for Blood-Borne Diseases via EM Residents.
AB - BACKGROUND: The emergency department (ED) is one of the high-risk places for
blood-borne disease (BBD) transmission. OBJECTIVES: This study aimed to assess
the rate of adherence to preventive measures (PM) against the blood-borne
diseases via emergency medicine (EM) residents. MATERIALS AND METHODS: In this
descriptive cross-sectional study, 80 emergency residents of an educational
public hospital were observed with regard to abiding by the preventive measures
from March to May 2010. RESULTS: Cleaning blood tainted skin before phlebotomy or
IV line preparation and hand washing before donning latex gloves achieved the
maximum (88/150) and minimum (0/150) scores. The most observed barriers of PM
were frequent attendance of patients (85%), work load (80%), and need to work
rapidly (68%). CONCLUSIONS: It seems that, the preventive instructions are not
optimally respected by ERs possibly due to the crowded wards, high work load and
the need to work rapidly.
PMID- 24350152
TI - Employing the Next Generation: Isn't it time to Make the Transition.
PMID- 24350153
TI - Mental Trauma Experienced by Caregivers of patients with Diffuse Axonal Injury or
Severe Traumatic Brain Injury.
AB - CONTEXT: As with care giving and rehabilitation in chronic illnesses, the concern
with traumatic brain injury (TBI), particularly with diffuse axonal injury (DAI),
is that the caregivers are so overwhelmingly involved in caring and
rehabilitation of the victim that in the process they become traumatized
themselves. This review intends to shed light on the hidden and silent trauma
sustained by the caregivers of severe brain injury survivors. Motor vehicle
accident (MVA) is the highest contributor of TBI or DAI. The essence of trauma is
the infliction of pain and suffering and having to bear the pain (i.e. by the TBI
survivor) and the burden of having to take care and manage and rehabilitate the
TBI survivor (i.e. by the TBI caregiver). Moreover many caregivers are not
trained for their care giving task, thus compounding the stress of care giving
and rehabilitating patients. Most research on TBI including DAI, focus on the
survivors and not on the caregivers. TBI injury and its effects and impacts
remain the core question of most studies, which are largely based on the
quantitative approach. EVIDENCE ACQUISITION: Qualitative research can better
assess human sufferings such as in the case of DAI trauma. While quantitative
research can measure many psychometric parameters to assess some aspects of
trauma conditions, qualitative research is able to fully reveal the meaning,
ramification and experience of TBI trauma. Both care giving and rehabilitation
are overwhelmingly demanding; hence , they may complicate the caregivers' stress.
However, some positive outcomes also exist. RESULTS: Caregivers involved in
caring and rehabilitation of TBI victims may become mentally traumatized.
Posttraumatic recovery of the TBI survivor can enhance the entire family's
closeness and bonding as well as improve the mental status of the caregiver.
CONCLUSIONS: A long-term longitudinal study encompassing integrated research is
needed to fully understand the traumatic experiences of caregivers. Unless
research on TBI or DAI trauma is given its proper attention, the burden of trauma
and injury on societies will continue to exacerbate globally.
PMID- 24350154
TI - Prehospital management of gunshot patients at major trauma care centers:
exploring the gaps in patient care.
AB - BACKGROUND: Prehospital management of gunshot-wounded (GW) patients influences
injury-induced morbidity and mortality. OBJECTIVES: To evaluate prehospital
management to GW patients emphasizing the protocol of patient transfer to
appropriate centers. PATIENTS AND METHODS: This prospective study, included all
GW patients referred to four major, level-I hospitals in Mashhad, Iran. We
evaluated demographic data, triage, transport vehicles of patients,
hospitalization time and the outcome. RESULTS: There were 66 GW patients. The
most affected body parts were extremities (60.6%, n = 40); 59% of cases (n = 39)
were transferred to the hospitals with vehicles other than an ambulance.
Furthermore, 77.3% of patients came to the hospitals directly from the site of
event, and 22.7% of patients were referred from other medical centers. EMS action
intervals from dispatchers to scene departure was not significantly different
from established standards; however, arrival to hospital took longer than optimal
standards. Additionally, time spent at emergency wards to stabilize vital signs
was significantly less in patients who were transported by EMS ambulances (P =
0.01), but not with private ambulances (P = 0.47). However, ambulance pre
hospital care was not associated with a shorter hospital stay. Injury Severity
was the only determinant of hospital stay duration (beta = 0.36, P = 0.01) in
multivariate analysis. CONCLUSIONS: GW was more frequent in extremities and the
most patients were directly transferred from the accident site. EMS (but not
private) ambulance transport improved patients' emergency care and standard time
intervals were achieved by EMS; however more than a half of the cases were
transferred by vehicles other than an ambulance. Nevertheless, ambulance
transportation (either by EMS or by private ambulance) was not associated with a
shorter hospital stay. This showed that upgrade of ambulance equipment and
training of private ambulance personnel may be needed.
PMID- 24350155
TI - Fixation of Intertrochanteric Fractures: Dynamic Hip Screw versus Locking
Compression Plate.
AB - BACKGROUND: According to the existing literature, the Dynamic Hip Screw (DHS) is
the preferred standard for the treatment of intertrochanteric fractures. However,
some surgeons use other devices such as the Locking Compression Plate (LCP).
OBJECTIVES: In this study, we compared the outcome of using DHS or LCP in
intertrochanteric fractures. MATERIALS AND METHODS: This cross-sectional study
was carried out on 104 patients who were referred to Pursina Hospital in Rasht,
Iran with intertrochanteric fractures of the femur treated with either the DHS or
LCP devices. Demographic features, existence or nonexistence of stability and
operating time were obtained from questionnaires. During a 6-month follow-up
after surgery, patients were interviewed to record variables such as Harris Hip
Scores and complications. The patients were also interviewed on their final visit
(between 9 and 31 postoperative months). The collected data was analyzed using
SPSS. RESULTS: We discovered that the number of incidences of limb shortening and
device failure was higher for patients treated with the LCP device (P = 0.048 and
P = 0.014). Patients treated with the DHS device had higher Harris Hip scores for
both the 6-month postoperative and the final evaluation visits (P = 0.01 and P =
0.018). CONCLUSIONS: Despite the complications of fixation with the DHS device,
it remains the most successful for treatment of intertrochanteric fractures.
PMID- 24350156
TI - Effects of taping on pain, grip strength and wrist extension force in patients
with tennis elbow.
AB - BACKGROUND: Tennis elbow (TE) is a common musculotendinous degenerative disorder
of the extensor origin at the lateral humeral epicondyle. Different modes of
treatment are used for management of tennis elbow. OBJECTIVES: This study
investigated the effect of the taping technique (TT) on pain, grip strength and
wrist extension force in treatment of tennis elbow. PATIENTS AND METHODS: Thirty
patients (16 men /14 women with a mean age of 32.2 years) with tennis elbow of
their dominant arm participated in this study. Outcome measures were assessment
of pain at the lateral aspect of the elbow, grip strength and wrist extension
force before and five to ten minutes after application of elbow tape on the
affected and unaffected arms. A Visual Analog Scale was used to assess pain. A
dynamometer and a hand-held dynamometer were used for evaluation of grip strength
and wrist extension force, respectively. RESULTS: Among the variables,
significant differences were found in wrist extension forces between effected and
unaffected arms (P = 0.02). Changes in grip strength showed statically
significant improvements in the affected arm compared to the unaffected arm (P =
0.03). Also, in assessment of pain at the lateral epicondyle, the mean change
between affected and unaffected arms was significant, with P = 0.001.
CONCLUSIONS: The taping technique, as applied in this study demonstrates an
impressive effect on wrist extension force and grip strength of patients with TE.
Elbow taping also reduces pain at the lateral aspect of the elbow in these
patients.
PMID- 24350157
TI - Behavior of healthcare workers after injuries from sharp instruments.
AB - BACKGROUND: Injuries with sharps are common occupational hazards for healthcare
workers. Such injuries predispose the staff to dangerous infections such as
hepatitis B, C and HIV. OBJECTIVES: The present study was conducted to
investigate the behaviors of healthcare workers in Kashan healthcare centers
after needle sticks and injuries with sharps in 2012. MATERIALS AND METHODS: A
cross-sectional study was conducted on 298 healthcare workers of medical centers
governed by Kashan University of Medical Sciences. A questionnaire was used in
this study. The first part included questions about demographic characteristics.
The second part of the questionnaire consisted of 16 items related to the sharp
instrument injuries. For data analysis, descriptive and analytical statistics
(chi-square, ANOVA and Pearson correlation coefficient) SPSS version 16.0
software was used. RESULTS: From a total of 298 healthcare workers, 114 (38.3%)
had a history of injury from needles and sharp instruments in the last six
months. Most needle stick and sharp instrument injuries had occurred among the
operating room nurses and midwifes; 32.5% of injuries from sharp instruments
occurred in the morning shift. Needles were responsible for 46.5% of injuries.
The most common actions taken after needle stick injuries were compression
(27.2%) and washing the area with soap and water (15.8%). Only 44.6% of the
injured personnel pursued follow-up measures after a needle stick or sharp
instrument injury. CONCLUSIONS: More than a half of the healthcare workers with
needle stick or sharp instrument injury had refused follow-up for various
reasons. The authorities should implement education programs along with protocols
to be implemented after needle stick injuries or sharps.
PMID- 24350158
TI - Mortality and morbidity of fireworks-related burns on the annual last wednesday
of the year festival (charshanbeh soori) in iran: an 11-year study.
AB - BACKGROUND: Management of firework-related injuries is costly for the patient,
society, and government. OBJECTIVES: Evaluating effective factors yielding to
such injuries may lead to better management of patients and decreased costs and
morbidities. PATIENTS AND MATERIALS: This retrospective cross-sectional study was
performed on burn patients referred to Shahid Motahari Burns Hospital on
Charshanbeh Soori day festival during the period extending from March 2000 to
March 2011 (11 days in an 11-year period). Demographic data, causes of burn
injury, severity, and affected body parts were recorded. Data were analyzed using
SPSS version 16. RESULTS: There were164 patients in the study with a mean age of
18.34 +/- 9.31 years; 87% (145/164) were male. Homemade grenades were the most
frequent cause of injury. Hand injury was reported in 56% (92/164) of the cases.
Amputation was executed in 7 (4.3%) cases, and 6 (3.7%) patients died due to
severe burn injuries and facial damage. CONCLUSIONS: Fireworks- related injuries
during Charshanbeh Soori ceremony causes significant morbidities and damage to
different body parts (especially upper limbs and face), and some of these
injuries will lead to life time disabilities, amputations, and even death. As
most of the injured patients are young teenagers and children, special
consideration must be taken into account to prevent long term morbidities.
PMID- 24350159
TI - Interpretation of Computed Tomography of the Head: Emergency Physicians versus
Radiologists.
AB - BACKGROUND: Many patients are brought to crowded emergency departments (ED) of
hospitals every day for evaluation of head injuries, headaches, neurologic
deficits etc. CT scan of the head is the most common diagnostic measure used to
search for pathologies. In many EDs the initial interpretation of images are
performed by emergency physicians (EP). Since most decisions are made based on
the initial interpretation of the images by emergency physicians and not the
radiologists, it is necessary to assess the accuracy of interpretations made by
the former group. OBJECTIVES: The objective of this study was to compare the
findings reported in the interpretation of head CTs by emergency physicians and
compare to radiologists (the gold standard). MATERIALS AND METHODS: This was a
prospective cross sectional study conducted from March to May 2009 in a teaching
hospital in Tehran, Iran. All non-contrast head CTs obtained during the study
period were copied on DVDs and sent separately to a radiologist, 6 emergency
medicine (EM) attending physicians and 14 senior EM residents for interpretation.
Clinical information pertaining to each patient was also sent with each CT. The
radiologist's interpretation was considered as the gold standard and reference
for comparison. Data from EM physicians and residents were compared with the
reference as well as with each other and statistical analysis was performed using
SPSS 18.5. RESULTS: Out of 544 CT scans, EM physicians had 35 false negatives and
53 false positives compared with radiologist's interpretations (P < 0.0001). EM
residents had 74 false negatives and 12 false positives compared with
radiologist's interpretations (P < 0.0001). CONCLUSIONS: Both EPs and ER
residents either missed or falsely called a significant number of pathologies in
their interpretations. The interpretations of EPs and ER residents were more
sensitive and more specific, respectively. These findings revealed the need for
increased training time in head CT reading for residents and the necessity of
attending continuing medical education workshops for emergency physicians.
PMID- 24350160
TI - Simultaneous bilateral fracture dislocation of the talus: a case report.
AB - INTRODUCTION: Fracture - dislocations of the talus are typically due to high
energy injuries. Displaced fracture - dislocations of the talus have poor
outcomes in general and complications are common. Although talar fracture is
common and comprises the second most common tarsal fracture, bilateral fracture -
dislocations of the talus are rare. Not many reports regarding the subject can be
found in the literature. CASE PRESENTATION: We report a patient with bilateral
fracture - dislocations of the talus treated by open reduction and internal
fixation. This patient was a 25 year-old man who sustained bilateral fracture -
dislocation of the talus due to a motor vehicle accident. CONCLUSIONS: Bilateral
talar fracture - dislocation is rare. The surgical approach discussed together
with the pathomechanics of this injury can yield good short term results.
PMID- 24350161
TI - Undetected Aorto-RV Fistula With Aortic Valve Injury and Delayed Cardiac
Tamponade following a Chest Stab Wound: A Case Report.
AB - INTRODUCTION: Although a few patients will survive after penetrating cardiac
injuries, some of them may have unnoticeable intracardiac injuries. The
combination of aorto-right ventricular fistula with aortic valve injury is rare.
CASE PRESENTATION: A 19 year-old man referred with an aorto-right ventricular
fistula accompanied with aortic regurgitation and delayed tamponade following a
stab in the chest. The patient was scheduled for fistula repair, aortic valve
replacement and pericardectomy two months after trauma. CONCLUSIONS: To prevent
missing intracardiac injury and also late cardiac injury complications, in all
pericordial stab wounds, serial clinical examinations and serial echocardiography
should be performed. In addition, cardiac injuries should be repaired during the
same hospital stay.
PMID- 24350162
TI - Spontaneous radial nerve palsy subsequent to non-traumatic neuroma.
AB - INTRODUCTION: Spontaneous radial palsy is a not rare finding in hand clinics. The
anatomy of the radial nerve renders it prone to pressure paralysis as often
called "Saturday night palsy". This problem is a transient nerve lesion and an
acute one but the case presented here is very unusual in that it seems this
entity can also occur as an acute on chronic situation with neuroma formation.
CASE PRESENTATION: A 61 year-old man presented with the chief complaint of
inability to extend the wrist and the fingers of the left hand which began
suddenly the night before admission, following a three-week history of pain,
numbness and tingling sensation of the affected extremity. He had no history of
trauma to the extremity. Electromyography revealed a severe conductive defect of
the left radial nerve with significant axonal loss at the upper arm. Surgical
exploration identified a neuroma of the radial nerve measuring 1.5 cm in length
as the cause of the paralysis. The neuroma was removed and an end-to-end nerve
coaption was performed. CONCLUSIONS: Complete recovery of the hand and finger
extension was achieved in nine months.
PMID- 24350163
TI - Queries regarding local erythropoietin injection in tibiofibular fracture
healing.
PMID- 24350164
TI - In Reply to: Queries Regarding Local Erythropoietin Injection in Tibiofibular
Fracture Healing.
PMID- 24350165
TI - Cardiac surgery: a matter of life or death.
PMID- 24350166
TI - Review of sport-induced groin injuries.
AB - CONTEXT: Groin injuries are among the most common injuries co-existing with
sports. The aim of this review was to outline the epidemiology and identify risk
factors, as well as examine preventative and interventional measures for reducing
the occurrence of this form of injury among athletes. EVIDENCE ACQUISITION: An
electronic, systematic search for relevant keywords, either separately or in
combination was sought in the academic scientific databases. RESULTS: Groin
injuries, acute or chronic, consist of a high percentage of injuries that
manifest with pain. Despite the specific tendency for injury among some sports,
such injuries make up 2-5% of sport-induced injuries. There are few available
reports on lower limb injuries, especially groin injuries, in Iran. Numerous
factors predispose to groin injuries. A lengthy list of preventive/ treatment
measures, from preliminary to sophisticated, have been proposed. CONCLUSIONS:
Although using a programmed strategy designed to decrease the risk of groin
injuries by taking a strategic approach to exercise may alleviate complications,
in some cases the chronic nature of the injury may threaten the professional life
of the athlete. More research is required to plan suitable programs for reducing
the risk of this type of injury in athletes.
PMID- 24350167
TI - Assessment of genitourinary trauma in southeastern iran.
AB - BACKGROUND: To survey genitourinary (GU) organ injury following general trauma,
we performed an epidemiologic study of urogenital injuries in trauma patients
referred to our hospital (a teaching hospital affiliated with the Zahedan
University of Medical Sciences). OBJECTIVES: We aimed to assess the epidemiology
of urogenital system injuries in southeastern Iran. PATIENTS AND METHODS: From
April 2009 to November 2011, all patients with GU injuries referred to our
hospital were studied. The data including age, sex, type of injury, mechanism of
trauma, and prognosis of patients was collected and analyzed. RESULTS: From a
total of 3450 patients, 66 (1.91%) had injuries of the urogenital system;
49(74.24%) were male and 17(25.75%) female. The patients' mean age was 23 +/- 12
years (range 2 to 75 years). Of these 66 patients, 61 (94.24%) had blunt trauma,
and 5 (7.57%) had penetrating trauma. Motor vehicle accidents were the most
common cause of trauma (63.63%). The most common injured organs were kidneys in
41 (62.12%) and the bladder in 9 (13.6%); 47 patients (71.21%) had associated
intra-abdominal injuries, and 42 (63.63%) had other accompanying injuries;
23(34.84%) patients required surgical intervention. Three patients (4.54%) died
due to the severity of injuries (Injury Severity Score > 12). CONCLUSIONS: In our
assessment, blunt trauma including road traffic accidents were the main cause of
urogenital injuries. Most patients with urogenital trauma had multiple injuries,
and required a multidisciplinary approach for management.
PMID- 24350168
TI - Fine needle aspiration: an atraumatic method to diagnose head and neck masses.
AB - BACKGROUND: Patients presenting with a mass require tissue biopsy for
histological diagnosis and treatment. Fine needle aspiration (FNA) is offered as
an atraumatic, well tolerated, and inexpensive method for obtaining a biopsy from
these lesions. OBJECTIVES: In this study we evaluated the accuracy of FNA as an
atraumatic method among patients with nonthyroidal masses for diagnosis of
neoplastic masses compared to open surgery. PATIENTS AND METHODS: In a cross
sectional study, 65 patients with a head and neck masses (nonthyroidal) referred
to us from 2004 to 2009. Those who had both FNA and open biopsy (the gold
standard) were assessed for specificity, sensitivity, positive and negative
predictive values of FNA in diagnoses. RESULTS: Sixty-five cases with both
definite diagnoses of open biopsy and FNA were assessed. The mean (+/- standard
deviation) age of patients was 39.96 +/- 19.69 years (range 10 to 82 years).
Twenty-five (40.8%) subjects were categorized as malignant neoplasms, 16 (19.4%)
as benign neoplasms, and 24 (39.8%) as non-neoplastic lesions. The sensitivity,
specificity, positive and also negative predictive values of FNA in the diagnosis
of neoplastic masses were 95%, 85%, 92.68%, and 91.66% respectively, and the
diagnostic accuracy was 92.3%. CONCLUSIONS: It seems that FNA is a useful
atraumatic diagnostic technique with a high diagnostic accuracy which can provide
a highly sensitive diagnosis with low false positive diagnoses in patients with
nonthyroidal masses.
PMID- 24350169
TI - Validation of the Iranian Version of the University of California at Los Angeles
Posttraumatic Stress Disorder Index for DSM-IV-R.
AB - BACKGROUND: Natural disasters, both expected and unexpected, usually cause
widespread injuries and destruction with a large number of survivors, including
children. Several studies have shown that children may develop posttraumatic
stress disorder after exposure to disasters such as an earthquake. OBJECTIVES:
This study aimed to evaluate the screening abilities of the University of
California at Los Angeles Posttraumatic Stress Disorder Index for DSM-IV
(Revision 1) (UCLA PTSD for DSM-IV) among Iranian school-aged children. PATIENTS
AND METHODS: Twenty months after the Qeshm Island 6.1-magnitude earthquake in
2008, we screened 50 students aged between 7 and 12 years for posttraumatic
stress disorder using the UCLA PTSD INDEX for DSM-IV. A Structured Clinical
Interview for DSM-IV criteria was used as the gold standard. RESULTS: The
internal consistency for all the scales was good and Cronbach's coefficient for
the overall items was 0.76. The sensitivity of this questionnaire was high
(0.96), while its specificity was moderate (0.50). CONCLUSIONS: The study
findings showed that the Iranian version of UCLA PTSD Index for DS-MIV-R was
appropriate for screening PTSD in children.
PMID- 24350170
TI - Amputation: a ten-year survey.
AB - BACKGROUND: Limb loss occurs due to different causes and has been increased in
many countries. It has without exception, great economic, psychological and
social impacts. OBJECTIVES: This study assesses the demographics of amputees in
one city of Iran. PATIENTS AND METHODS: This retrospective study was undertaken
on all of the amputees between April 2002 and December 2011. Patients'
demographics including age, sex, the amputated limb, etiology of limb loss and
level of amputation were recorded. RESULTS: We had 216 patients in the study. The
average number of amputations was 21.6 per year and varied from 14 to 32. The
mean age of amputation was 39.26+/- 12.6 years. Of the patients, 172 were male
(79.62%) and 44 female (20.37%); 119 of the amputations (55.09 %) were major and
97 minor (44.9 %). The most common cause of amputation was trauma and the most
common was the toe. In trauma patients the mean age was 38.12+/- 10.25 years and
98 (83.7%) were male. CONCLUSIONS: In contrast to similar studies in developed
countries, trauma was found to be the major cause of all types of amputations.
Results of this study may be used in prevention planning.
PMID- 24350171
TI - Knee Flexion Strength Before and After ACL Reconstruction Using Hamstring Tendon
Autografts.
AB - BACKGROUND: Anterior cruciate ligament (ACL) injury is the most common sports
injury in both athletes and nonathletes; it can cause disability if not treated
correctly. In cases with minor injuries, conservative treatments suffice. But, in
cases with ACL tear, surgery by different methods and autografts are indicated.
The most prevalent method for ACL reconstruction is the use of hamstring tendon
autograft; this requires tendon removal and results in subsequent weakness in
patient's knee flexion strength which can cause dissatisfaction. OBJECTIVES: In
this study we evaluate a common procedure used for treating ACL injuries.
PATIENTS AND METHODS: This study was performed at a hospital in Tehran on 30
patients with ACL tears. Patients' knee flexion strengths before and 2, 4, 6, and
12 months after reconstruction were measured separately at 20, 45, 90, and 110
knee flexion angles, and their means were analyzed using paired t-test. RESULTS:
In this study, knee flexion strength decreased after ACL reconstruction. The
greatest decrease in knee flexion strength was observed at 90 and 110 knee
flexion angles. CONCLUSIONS: Some previous studies have confirmed reduced knee
flexion strength following ACL reconstruction at high knee flexion angles.
However, some others have denied it. The present study confirmed the reduction in
knee flexion strength one year after ACL reconstruction at 90 and 110 flexion
angles (P = 0.000). Furthermore, the need for physiotherapy, as a process for
rehabilitating these patients was also confirmed.
PMID- 24350172
TI - Comparison of harrington rod and cotrel-dubousset devices in surgical correction
of adolescent idiopathic scoliosis.
AB - BACKGROUND: Since the time of Paul Harrington numerous implants have been
introduced for correction of scoliosis, but none are ideal. Newer devices are
very expensive, and in our country some patients cannot afford them. OBJECTIVES:
The aim of this study was to compare the results of the Harrington rod (HR)
device and the newer Cotrel-Dubousset (CD) device in treatment of adolescent
idiopathic scoliosis (AIS). MATERIALS AND METHODS: A retrospective review
assessed patients with AIS admitted for spinal curve correction treated with HR
(n = 120) and CD devices (n = 138) between October 1988 to April 2001 at the
Shafa Yahyaeian Hospital, Tehran, Iran. We extracted information from the
patient's file and radiographs before, after and two years post-operation.
RESULTS: The mean age of patients was 16.7 +/- 2.5 years. There was no
statistically significant difference between the two groups regarding gender,
age, curve before surgery, and percentage of flexibility. The mean curvature was
70 +/- 20.7 in the HR and 64.81 +/- 19.4 in the CD group before surgery (P =
0.09); and the mean curvature was 40 +/- 16.3 and 26.58 +/- 15.37 in HR and CD
groups respectively after surgery (P = 0.156). The mean curvature was 47.2 +/-
15.9 in HR and 31.2 +/- 15.4 in CD groups at two years follow-up (P = 0.156).
CONCLUSIONS: Results of many studies have shown no significant impairment in long
term quality of life and function in patients treated with Harrington rods.
According to previously performed studies and the current study, surgical
correction with Harrington rods seem to be comparable with the newer more
expensive CD device. Although there is no doubt that the preference is to use
newer devices in view of some disadvantages of HR, but this does not preclude
using it for patients that cannot afford the newer devices.
PMID- 24350173
TI - Cholestasis in a three year-old child following abdominal blunt trauma: a case
report.
AB - INTRODUCTION: Extra-hepatic bile duct injuries in children following blunt
abdominal trauma are rare; early diagnosis and treatment are imperative for a
good outcome. The purpose of this report is to describe the management of
problems encountered in children with bile duct injuries following blunt
abdominal trauma. CASE PRESENTATION: A three year-old girl presented with
obstructive jaundice and vomiting following blunt abdominal trauma one month
prior to referral. The child was sitting in her father's lap when the accident
occurred. She was then examined by an emergency physician to assess the cause of
vomiting. An abdominal ultrasonography was performed and revealed dilatation of
the common bile duct. CONCLUSIONS: To the best of our knowledge, this is the
first report of bile duct injury following blunt trauma and its emergency
management.
PMID- 24350174
TI - Hypokalemia-induced abnormal movements: case report.
AB - INTRODUCTION: A sudden loss of consciousness followed by abnormal movements can
be ictal or syncopal in origin. Transient response by the brain to sudden
decrease of blood flow may cause sudden loss of consciousness followed by
abnormal movements that mimic seizure. Dysrhythmia is one of the important and
critical reasons of such events that should be differentiated from seizure. CASE
PRESENTATION: In this case report we describe a 55 year-old woman admitted to our
emergency department first with the impression of seizure. Eventually, it was
realized that she had suffered from brain hypo-perfusion secondary to hypokalemia
induced arrhythmia. Her arrhythmia was managed by unsynchronized biphasic shock
in acute phase and also potassium replacement. She was then admitted to the CCU
(Coronary Care Unit) where she received further care for medical management and
drug dose adjustment and was discharged 4 days later. CONCLUSIONS: Syncope from
arrhythmia most commonly results from ventricular tachycardia, which accounts for
11% of all cases of syncope. Torsades de point is a unique type of ventricular
tachycardia, characterized by QRS complexes of changing amplitude proceeded by
prolonged QT intervals and almost often followed by loss of consciousness and
also seizure like movements. Prolonged QT interval which is an important
provocative factor for torsades de point commonly results from interactions
between drug therapy, myocardial ischemia, and electrolyte disturbances such as
hypokalemia or hypomagnesaemia. Changes in the extracellular potassium level have
predominant and profound influences on the function of the cardiovascular system
that may provoke fatal demonstrations such as QT prolongation, ventricular
arrhythmia and even cardiac arrest. Electrolyte assessment is particularly
important in certain patient populations, such as the elderly in whom a variety
of pathological states or conditions like dehydration or renal failure are more
common. Early identification and correction of these disturbances are necessary
to control either seizures or seizure-like movements and prevent permanent brain
damage, as anticonvulsants alone are generally ineffective.
PMID- 24350175
TI - Child health and human development over the lifespan.
PMID- 24350176
TI - Alcohol-related content of animated cartoons: a historical perspective.
AB - This study, based on a stratified (by decade of production) random sample of
1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks
to determine the prevalence of alcohol-related content; how, if at all, the
prevalence changed between 1930 and 1996 (the years spanned by this research);
and the types of messages that animated cartoons convey about beverage alcohol
and drinking in terms of the characteristics that are associated with alcohol
use, the contexts in which alcohol is used in cartoons, and the reasons why
cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was
found to contain alcohol-related content, indicating that the average child or
adolescent viewer is exposed to approximately 24 alcohol-related messages each
week just from the cartoons that he/she watches. Data indicated that the
prevalence of alcohol-related content declined significantly over the years.
Quite often, alcohol consumption was shown to result in no effects whatsoever for
the drinker, and alcohol use often occurred when characters were alone. Overall,
mixed, ambivalent messages were provided about drinking and the types of
characters that did/not consume alcoholic beverages.
PMID- 24350177
TI - Grand challenge: understanding survival paradoxes in epidemiology.
PMID- 24350178
TI - Trends in neuropediatric physical therapy.
PMID- 24350179
TI - The infectious disease challenges of our time.
PMID- 24350180
TI - Public health in a global context.
PMID- 24350181
TI - Daily walking and life expectancy of elderly people in the iowa 65+ rural health
study.
AB - The purpose of this paper is to investigate the hypothesis that outdoor daily
walking, as an exercise, has an effect on the rate of mortality among those
elderly people in the Iowa 65+ Rural Health Study (RHS). RHS is a prospective
longitudinal cohort study of 8 years follow-up from 1981 to 1989. It consists of
a random sample of 3,673 individuals (1,420 men and 2,253 women) aged 65 or older
living in Washington and Iowa counties of the State of Iowa. Our analysis was
conducted only on those non-institutional individuals who could without any help
walk across a small room; this reduced the total number of individuals in the
study to 2,717. Moreover, a total of 923 individuals died during the period of
the study. The life histories of those individuals were obtained and divided into
two cohorts; one containing 1,134 who exercise daily by walking and the other
containing 1,583 who do not exercise daily by walking. The interviewers asked
participants about 17 medical conditions, from which 13 are included in our
study. We found that daily walking exercise is related inversely to total
mortality before and after adjusting for the other factors in particular for age
group and health conditions. We observed that hazard ratio (HR) of death was the
highest among those individuals having a history of cancer (HR = 2.971) and
history of stroke (HR = 2.127). However, individuals with a history of stroke in
the "daily walking group" have HR = 0.856 and their risk of death were reduced by
81% compared to those in no "daily walking group."
PMID- 24350182
TI - Challenging behavior and related factors in people with intellectual disability
living in residential care centers in Israel.
AB - INTRODUCTION: Adults with intellectual disabilities have higher rates of mental
ill-health and problem behaviors than the general population. METHOD: In this
study, we present data on trends in challenging behavior in residential care
centers in Israel from 1998 to 2008 and further data on trends in employment of
psychiatrists from 1998 to 2009 and psychotropic medication use from 1998 to
2008. Data was collected from annual questionnaires sent out to all residential
care centers in Israel, from the Office of the Medical Director, Division for
Intellectual and Developmental Disabilities, Ministry of Social Affairs and
Social Services. RESULTS: Rates of challenging behaviors in people with
intellectual disabilities living in residential care centers in Israel continues
to rise. Alongside this, trends in regular psychotropic medication use also
continues to increase. CONCLUSION: Consideration of biological, psychological,
social, and environmental factors in the assessment and management of people with
intellectual disabilities and challenging behaviors is important. This is best
conducted using a multidisciplinary approach, which may include psychiatric
assessment. Non-pharmacological interventions should always be considered either
alongside, or instead of medication.
PMID- 24350183
TI - Randomized controlled trial designs for operations research in low-income
countries: reality or delusion?
PMID- 24350184
TI - Self-rated health and public health: a critical perspective.
PMID- 24350185
TI - Associations of adiponectin and leptin with incident coronary heart disease and
ischemic stroke in african americans: the jackson heart study.
AB - BACKGROUND: Because the predictive significance of previously reported racial
differences in leptin and adiponectin levels remains unclear, we assessed the
prospective association of these adipokines with the risk of cardiovascular
disease (CVD) events in African Americans, a population with a high prevalence of
cardiometabolic risk factors. METHODS: Serum specimens from 4,571 Jackson Heart
Study participants without prevalent CVD at baseline examination (2000-2004) were
analyzed for adiponectin and leptin levels. Cox proportional hazard regression
models were used to estimate the associations of the two adipokines with incident
coronary heart disease (CHD) and incident ischemic stroke. RESULTS: During 6.2
years average of follow-up, 98 incident CHD and 87 incident ischemic stroke
events were documented. Among study participants (64% women; mean age 54 +/- 13
years), the mean (standard deviation, SD) was 6.04 (4.32) MUg/mL in women and
4.03 (3.14) MUg/mL in men for adiponectin and 37.35 (23.90) ng/mL in women and
11.03 (10.05) ng/mL in men for leptin. After multivariable adjustment that
included age, body mass index, high-density lipoprotein cholesterol,
triglycerides, C-reactive protein, insulin resistance by homeostasis model
assessment for insulin resistance, systolic blood pressure, hypertension
medication, smoking, and physical activity, adiponectin was directly associated
in women with incident stroke, HR = 1.41 (1.04-1.91) per one SD increase (p =
0.03), but not in men (p = 0.42). It was not associated with incident CHD in
women or men. Leptin was not associated with incident CHD or incident stroke.
CONCLUSION: In the largest community-based African American cohort, adiponectin
was associated among women with a higher risk of incident stroke. Whether
adiponectin harbors harmful properties, or it is produced in response to vascular
inflammation to counter the atherosclerotic process, or the putative "adiponectin
resistance" phenomenon acts, should be further assessed.
PMID- 24350186
TI - Early life factors and risk of childhood rhabdomyosarcoma.
AB - Although little is known about etiology of childhood rhabdomyosarcoma (RMS),
early life factors are suspected in the etiology. We explored this hypothesis
using linked data from the California Cancer Registry and the California birth
rolls. Incident cases were 359 children <6-year-old (218 embryonal, 81 alveolar,
60 others) diagnosed in 1988-2008. Controls (205, 173), frequency matched on
birth year (1986-2007), were randomly selected from the birth rolls. We examined
association of birth characteristics such as birth weight, size for gestational
age, and timing of prenatal care with all-type RMS, embryonal, and alveolar
subtypes. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95%
CIs) were estimated using logistic regression. In contrast to a previous study,
we observed statistically non-significant association for embryonal subtype among
high birth weight (4000-5250 g) children for term births [OR (95% CI): 1.28
(0.85, 1.92)] and all births adjusted for gestational age [OR (95% CI): 1.21
(0.81, 1.81)]. On the other hand, statistically significant 1.7-fold increased
risk of alveolar subtype (95% CI: 1.02, 2.87) was observed among children with
late or no prenatal care and a 1.3-fold increased risk of all RMS subtypes among
children of fathers >=35 years old at child birth (95% CI: 1.00, 1.75),
independent of all covariates. Our finding of positive association on male sex
for all RMS types is consistent with previous studies. While we did not find a
convincingly positive association between high birth weight and RMS, our findings
on prenatal care supports the hypothesis that prenatal environment modifies risk
for childhood RMS.
PMID- 24350187
TI - Epidemiology and economic impact of celiac disease in the South vesuvian area of
naples: a survey.
PMID- 24350189
TI - Educating the public health workforce.
PMID- 24350188
TI - Alpha-1 antitrypsin reduces severity of pseudomonas pneumonia in mice and
inhibits epithelial barrier disruption and pseudomonas invasion of respiratory
epithelial cells.
AB - Nosocomial pneumonia (NP) is the third most common hospital-acquired infection
and the leading cause of death due to hospital-acquired infection in the US.
During pneumonia and non-pneumonia severe illness, respiratory tract secretions
become enriched with the serine protease neutrophil elastase (NE). Several NE
activities promote onset and severity of NP. NE in the airways causes proteolytic
tissue damage, augments inflammation, may promote invasion of respiratory
epithelium by bacteria, and disrupts respiratory epithelial barrier function.
These NE activities culminate in enhanced bacterial replication, impaired gas
exchange, fluid intrusion into the airways, and loss of bacterial containment
that can result in bacteremia. Therefore, neutralizing NE activity may reduce the
frequency and severity of NP. We evaluated human alpha-1 antitrypsin (AAT), the
prototype endogenous NE inhibitor, as a suppressor of bacterial pneumonia and
pneumonia-related pathogenesis. In AAT(+/+) transgenic mice that express human
AAT in lungs, mortality due to Pseudomonas aeruginosa (P.aer) pneumonia was
reduced 90% compared to non-transgenic control animals. Exogenous human AAT given
to non-transgenic mice also significantly reduced P.aer pneumonia mortality.
P.aer-infected AAT(+/+) mice demonstrated reduced lung tissue damage, decreased
bacterial concentrations in lungs and blood, and diminished circulating cytokine
concentrations compared to infected non-transgenic mice. In vitro, AAT suppressed
P.aer internalization into respiratory epithelial cells and inhibited NE or P.aer
induced disruption of epithelial cell barrier function. The beneficial effects of
human AAT in murine P.aer pneumonia raise the possibility of AAT use as a
prophylactic treatment for NP in humans, and suggest a role for AAT as an innate
immune mediator.
PMID- 24350190
TI - Development and Assessment of Traditional and Innovative Media to Reduce
Individual HIV/AIDS-Related Stigma Attitudes and Beliefs in India.
AB - Although stigma is considered a major barrier to effective response to the
HIV/AIDS epidemic, there is a lack of evidence on effective interventions. This
media intervention took place among key HIV-vulnerable communities in Southern
India. Two HIV stigma videos were created using techniques from traditional film
production and new media digital storytelling. A series of 16 focus group
discussions were held in 4 rural and 4 urban sites in South India, with specific
groups for sex workers, men who have sex with men, young married women, and
others. Focus groups with viewers of the traditional film (8 focus groups, 80
participants) and viewers of the new media production (8 focus groups, 69
participants) revealed the mechanisms through which storyline, characters, and
esthetics influence viewers' attitudes and beliefs about stigma. A comparative
pre-/post-survey showed that audiences of both videos significantly improved
their stigma scores. We found that a simple illustrated video, produced on a
limited budget by amateurs, and a feature film, produced with an ample budget by
professionals, elicited similar responses from audiences and similar positive
short-term outcomes on stigma.
PMID- 24350191
TI - The Integration of the Neurosciences, Child Public Health, and Education
Practice: Hemisphere-Specific Remediation Strategies as a Discipline Partnered
Rehabilitation Tool in ADD/ADHD.
AB - ADD/ADHD is the most common and most studied neurodevelopmental problem. Recent
statistics from the U.S. Center for Disease Control state that 11% or
approximately one out of every nine children in the US and one in five high
school boys are diagnosed with ADD/ADHD. This number is thought to be increasing
at around 15-20% per year. The US National Institute of Mental Health's Multi
modal Treatment Study has shown that medication has no long-term benefit for
those with ADHD. To effectively address ADD/ADHD from within the framework of
child public health, an interdisciplinary strategy is necessary that is based on
a neuroeducational model that can be readily implemented on a large-scale within
the educational system. This study is based on previous findings that ADD/ADHD
children possess underactivity between sub-cortical and cortical regions. An
imbalance of activity or arousal in one area can result in functional
disconnections similar to that seen in split-brain patients. Since ADD/ADHD
children exhibit deficient performance on tests developed to measure perceptual
laterality, evidence of weak laterality or failure to develop laterality has been
found across various modalities (auditory, visual, tactile). This has reportedly
resulted in abnormal cerebral organization and ineffective cortical
specialization necessary for the development of language and non-language
function. This pilot study examines groups of ADD/ADHD and control elementary
school children all of whom were administered all of the subtests of the Wechsler
Individual Achievement Tests, the Brown Parent Questionnaire, and given objective
performance measures on tests of motor and sensory coordinative abilities.
Results measured after a 12-week remediation program aimed at increasing the
activity of the hypothesized underactive right hemisphere function, yielded
significant improvement of greater than 2 years in grade level in all domains
except in mathematical reasoning. The treated group also displayed a significant
improvement in behavior with a reduction in Brown scale behavioral scores. Non
treated control participants did not exhibit significant differences during the
same 12 week period in academic measurements. Controls were significantly
different from treatment participants in all domains after a 12-week period. The
non-treatment group also demonstrated an increase in behavioral scores and
increased symptoms of ADD/ADHD over the same time period when compared to the
treated group. Results are discussed in the context of the concept of functional
disconnectivity in ADD/ADHD children.
PMID- 24350192
TI - Beyond misconceptions: assessing pain in children with mild to moderate
intellectual disability.
AB - To assess and manage pain in children and adolescents with mild to moderate
intellectual disability, healthcare providers need access to updated tools and
current knowledge. Recent studies show that these children can verbally express
pain and use self-assessment tools accurately. Moreover, they know pain coping
strategies. Finally, they show mental imaging skills and are able to recall
autobiographical memories. These new data suggest that such children and
adolescents could be candidates to for hypno-analgesia protocols and behavioral
relaxation.
PMID- 24350193
TI - Geriatric workforce capacity: a pending crisis for nursing home residents.
AB - INTRODUCTION: The nursing home (NH) population in the US has grown to 1.6 million
people and is expected to double by 2030. While 88.3% of NH residents are over
65, the elders aged 85 and more have become the principal group. This demographic
change has increased the already high rates of chronic diseases and functional
disabilities in NH residents. METHODS: This study reviewed the supply of
geriatricians in addressing the growing healthcare needs of NH residents.
RESULTS: English-written articles between 1989 and 2012 were reviewed. Trend data
demonstrate that the geriatrician workforce has decreased from 10,270 in 2000 to
8,502 in 2010. Further, the pipeline analysis of physicians projected to receive
board certification in geriatrics (and maintain this certification) indicates a
worsening of the already insufficient supply of geriatricians for this vulnerable
population. CONCLUSION: Strategies to attract and maintain a geriatrician
workforce are imperative to avert a mounting crisis in the geriatric care in NH
and, by extension, other living settings.
PMID- 24350194
TI - The utility of intravenous acetaminophen in the perioperative period.
AB - Intravenous acetaminophen (IVA) has rapid and effective analgesic properties.
Recent studies have shown several benefits of using IVA perioperatively. However,
due to its relatively high cost and limited clinical data concerning its efficacy
compared with other agents, physicians are hesitant to use IVA in the
perioperative period. This brief review examines the utility of this medication
in the perioperative period and highlights future areas of clinical and
epidemiological research regarding its use.
PMID- 24350195
TI - Application of situational leadership to the national voluntary public health
accreditation process.
AB - Successful navigation through the accreditation process developed by the Public
Health Accreditation Board (PHAB) requires strong and effective leadership.
Situational leadership, a contingency theory of leadership, frequently taught in
the public health classroom, has utility for leading a public health agency
through this process. As a public health agency pursues accreditation, staff
members progress from being uncertain and unfamiliar with the process to being
knowledgeable and confident in their ability to fulfill the accreditation
requirements. Situational leadership provides a framework that allows leaders to
match their leadership styles to the needs of agency personnel. In this paper,
the application of situational leadership to accreditation is demonstrated by
tracking the process at a progressive Kentucky county public health agency that
served as a PHAB beta test site.
PMID- 24350196
TI - Promoting health equity: a new challenge for frontiers in public health.
PMID- 24350197
TI - Mapping avian influenza transmission risk at the interface of domestic poultry
and wild birds.
AB - Emergence of avian influenza viruses with high lethality to humans, such as the
currently circulating highly pathogenic A(H5N1) (emerged in 1996) and A(H7N9)
cause serious concern for the global economic and public health sectors.
Understanding the spatial and temporal interface between wild and domestic
populations, from which these viruses emerge, is fundamental to taking action.
This information, however, is rarely considered in influenza risk models, partly
due to a lack of data. We aim to identify areas of high transmission risk between
domestic poultry and wild waterfowl in China, the epicenter of both viruses. Two
levels of models were developed: one that predicts hotspots of novel virus
emergence between domestic and wild birds, and one that incorporates H5N1 risk
factors, for which input data exists. Models were produced at 1 and 30 km spatial
resolution, and two temporal seasons. Patterns of risk varied between seasons
with higher risk in the northeast, central-east, and western regions of China
during spring and summer, and in the central and southeastern regions during
winter. Monte-Carlo uncertainty analyses indicated varying levels of model
confidence, with lowest errors in the densely populated regions of eastern and
southern China. Applications and limitations of the models are discussed within.
PMID- 24350198
TI - Assessing the Relationship between the Baseline Value of a Continuous Variable
and Subsequent Change Over Time.
AB - Analyzing the relationship between the baseline value and subsequent change of a
continuous variable is a frequent matter of inquiry in cohort studies. These
analyses are surprisingly complex, particularly if only two waves of data are
available. It is unclear for non-biostatisticians where the complexity of this
analysis lies and which statistical method is adequate. With the help of
simulated longitudinal data of body mass index in children, we review statistical
methods for the analysis of the association between the baseline value and
subsequent change, assuming linear growth with time. Key issues in such analyses
are mathematical coupling, measurement error, variability of change between
individuals, and regression to the mean. Ideally, it is better to rely on
multiple repeated measurements at different times and a linear random effects
model is a standard approach if more than two waves of data are available. If
only two waves of data are available, our simulations show that Blomqvist's
method - which consists in adjusting for measurement error variance the estimated
regression coefficient of observed change on baseline value - provides accurate
estimates. The adequacy of the methods to assess the relationship between the
baseline value and subsequent change depends on the number of data waves, the
availability of information on measurement error, and the variability of change
between individuals.
PMID- 24350199
TI - Depression and antidepressants: a nordic perspective.
PMID- 24350201
TI - Adolescence, violence, and public health.
PMID- 24350203
TI - Unprotected anal Intercourse among Iranian Intra-Venous Drug Users.
AB - PURPOSE: To assess the prevalence and associated factors of unprotected anal
intercourse among Iranian male heterosexual Intra-Venous Drug Users (IDUs).
METHODS: In a cross-sectional study 360 male heterosexual IDUs were sampled from
streets of eight different geographical parts of Iran. Variables such as socio
demographics, HIV knowledge (10 items), and HIV attitude (16 items) were entered
to a logistic regression to determine the predictors of unprotected anal
intercourse during the past month. RESULTS: From all, 20.8% reported unprotected
anal intercourse during the past month. HIV knowledge was not significantly
different among IDUs with and without unprotected anal intercourse. High age
[odds ratio (OR) = 0.954, 95% confidence intervals (CI) = 0.916-0.992] was
associated with a lower likelihood of unprotected anal intercourse, while being
not married (OR = 2.301, 95% CI = 1.151-4.601), and high perceived HIV risk (OR =
1.776, 95% CI = 1.376-2.290) were associated with a higher likelihood of
unprotected anal intercourse. CONCLUSION: Although the results might not be
generalizable to all Iranian IDUs, this study findings may still be helpful for
design and implementation of public health programs in Iran to prevent sexual
transmission of HIV through IDUs.
PMID- 24350204
TI - Exploring Perception of Indians about Plain Packaging of Tobacco Products: A
Mixed Method Research.
AB - This study assessed perceptions and support among the Indian populace about plain
packaging for all tobacco products. Twelve focus group discussions (n = 124),
stakeholder analysis with 24 officials and an opinion poll with 346 participants
were conducted between December 2011 and May 2012, Delhi. Plain packages for
tobacco products were favored by majority of participants (69%) and key
stakeholders (92%). The majority of participants perceived that plain packaging
would reduce the appeal and promotional value of the tobacco pack (>80%), prevent
initiation of tobacco use among children and youth (>60%), motivate tobacco users
to quit (>80%), increase notice ability, and effectiveness of pictorial health
warnings on tobacco packs (>90%), reduce tobacco usage (75% of key stakeholders).
Majority of participants favored light gray color for plain packaging. This study
provides key evidence to advocate with Indian Government and other countries in
South Asia region to introduce plain packaging legislation for all tobacco
products.
PMID- 24350202
TI - Perceived Risk Modifies the Effect of HIV Knowledge on Sexual Risk Behaviors.
AB - BACKGROUND: There is a large controversy in the literature about the inter
relations between perceived risk, knowledge, and risk behavior in different
settings, and people at HIV risk are not an exception. AIM: To assess additive
and multiplicative effect of perceived HIV risk and HIV knowledge on sexual risk
behavior of Injecting Drug Users (IDUs). METHOD: We enrolled 162 street based
IDUs to this analysis. Data came from a national survey of IDUs in Iran, with a
cross sectional design. Socio-demographics (employment, education, marital
status), HIV knowledge, perceived HIV risk, and four different sexual risk
behavior were registered. In the first step, using spearman test, the association
of HIV knowledge and risk behavior were tested, then possible moderating effect
of perceived HIV risk on this association was determined. RESULTS: Although among
IDUs with low perceived HIV risk, HIV knowledge was negatively associated with
sexual risk behavior (P < 0.05 for all), this association was not significant
among IDUs with high perceived HIV risk (P > 0.05 for all). Thus perceived HIV
risk moderated the association between HIV knowledge and sexual risk behavior.
CONCLUSION: Perceived risk should be taken into consideration when studying the
effect of HIV knowledge on sexual risk behavior of IDUs. Findings may help us
better understand negative effects of fear arousing interventions as a part of
HIV prevention media campaigns.
PMID- 24350205
TI - Telephone Surveys Underestimate Cigarette Smoking among African-Americans.
AB - BACKGROUND: This study tested the hypothesis that data from random digit-dial
telephone surveys underestimate the prevalence of cigarette smoking among African
American adults. METHOD: A novel, community-sampling method was used to obtain a
statewide, random sample of N = 2118 California (CA) African-American/Black
adults, surveyed door-to-door. This Black community sample was compared to the
Blacks in the CA Health Interview Survey (N = 2315), a statewide, random digit
dial telephone survey conducted simultaneously. RESULTS: Smoking prevalence was
significantly higher among community (33%) than among telephone survey (19%)
Blacks, even after controlling for sample differences in demographics.
CONCLUSION: Telephone surveys underestimate smoking among African-Americans and
probably underestimate other health risk behaviors as well. Alternative methods
are needed to obtain accurate data on African-American health behaviors and on
the magnitude of racial disparities in them.
PMID- 24350200
TI - A review of traditional and novel treatments for seizures in autism spectrum
disorder: findings from a systematic review and expert panel.
AB - Despite the fact that seizures are commonly associated with autism spectrum
disorder (ASD), the effectiveness of treatments for seizures has not been well
studied in individuals with ASD. This manuscript reviews both traditional and
novel treatments for seizures associated with ASD. Studies were selected by
systematically searching major electronic databases and by a panel of experts
that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone
carefully controlled trials in ASD, but these trials examined outcomes other than
seizures. Several lines of evidence point to valproate, lamotrigine, and
levetiracetam as the most effective and tolerable AEDs for individuals with ASD.
Limited evidence supports the use of traditional non-AED treatments, such as the
ketogenic and modified Atkins diet, multiple subpial transections,
immunomodulation, and neurofeedback treatments. Although specific treatments may
be more appropriate for specific genetic and metabolic syndromes associated with
ASD and seizures, there are few studies which have documented the effectiveness
of treatments for seizures for specific syndromes. Limited evidence supports l
carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and
dysfunction, folinic acid in cerebral folate abnormalities and early treatment
with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence
for a number of novel treatments, particularly magnesium with pyridoxine, omega-3
fatty acids, the gluten-free casein-free diet, and low-frequency repetitive
transcranial magnetic simulation. Zinc and l-carnosine are potential novel
treatments supported by basic research but not clinical studies. This review
demonstrates the wide variety of treatments used to treat seizures in individuals
with ASD as well as the striking lack of clinical trials performed to support the
use of these treatments. Additional studies concerning these treatments for
controlling seizures in individuals with ASD are warranted.
PMID- 24350206
TI - Nutrition training improves health workers' nutrition knowledge and competence to
manage child undernutrition: a systematic review.
AB - BACKGROUND: Medical and nursing education lack adequate practical nutrition
training to fit the clinical reality that health workers face in their practices.
Such a deficit creates health workers with poor nutrition knowledge and child
undernutrition management practices. In-service nutrition training can help to
fill this gap. However, no systematic review has examined its collective
effectiveness. We thus conducted this study to examine the effectiveness of in
service nutrition training on health workers' nutrition knowledge, counseling
skills, and child undernutrition management practices. METHODS: We conducted a
literature search on nutrition interventions from PubMed/MEDLINE, CINAHL, EMBASE,
ISI Web of Knowledge, and World Health Organization regional databases. The
outcome variables were nutrition knowledge, nutrition-counseling skills, and
undernutrition management practices of health workers. Due to heterogeneity, we
conducted only descriptive analyses. RESULTS: Out of 3910 retrieved articles, 25
were selected as eligible for the final analysis. A total of 18 studies evaluated
health workers' nutrition knowledge and showed improvement after training. A
total of 12 studies with nutrition counseling as the outcome variable also showed
improvement among the trained health workers. Sixteen studies evaluated health
workers' child undernutrition management practices. In all such studies, child
undernutrition management practices and competence of health workers improved
after the nutrition training intervention. CONCLUSION: In-service nutrition
training improves quality of health workers by rendering them more knowledge and
competence to manage nutrition-related conditions, especially child
undernutrition. In-service nutrition training interventions can help to fill the
gap created by the lack of adequate nutrition training in the existing medical
and nursing education system. In this way, steps can be taken toward improving
the overall nutritional status of the child population.
PMID- 24350207
TI - Families Enriched for Exceptional Longevity also have Increased Health-Span:
Findings from the Long Life Family Study.
AB - Hypothesizing that members of families enriched for longevity delay morbidity
compared to population controls and approximate the health-span of centenarians,
we compared the health-spans of older generation subjects of the Long Life Family
Study (LLFS) to controls without family history of longevity and to centenarians
of the New England Centenarian Study (NECS) using Bayesian parametric survival
analysis. We estimated hazard ratios, the ages at which specific percentiles of
subjects had onsets of diseases, and the gain of years of disease-free survival
in the different cohorts compared to referent controls. Compared to controls,
LLFS subjects had lower hazards for cancer, cardiovascular disease, severe
dementia, diabetes, hypertension, osteoporosis, and stroke. The age at which 20%
of the LLFS siblings and probands had one or more age-related diseases was
approximately 10 years later than NECS controls. While female NECS controls
generally delayed the onset of age-related diseases compared with males controls,
these gender differences became much less in the older generation of the LLFS and
disappeared amongst the centenarians of the NECS. The analyses demonstrate
extended health-span in the older subjects of the LLFS and suggest that this
aging cohort provides an important resource to discover genetic and environmental
factors that promote prolonged health-span in addition to longer life-span.
PMID- 24350208
TI - Improved confidence intervals of a small probability from pooled testing with
misclassification.
AB - This article concerns construction of confidence intervals for the prevalence of
a rare disease using Dorfman's pooled testing procedure when the disease status
is classified with an imperfect biomarker. Such an interval can be derived by
converting a confidence interval for the probability that a group is tested
positive. Wald confidence intervals based on a normal approximation are shown to
be inefficient in terms of coverage probability, even for relatively large number
of pools. A few alternatives are proposed and their performance is investigated
in terms of coverage probability and length of intervals.
PMID- 24350209
TI - Firesetting in childhood and adolescence.
PMID- 24350210
TI - Human sexuality and adolescence.
PMID- 24350213
TI - Disaster and emergency medicine - a conceptual introduction.
PMID- 24350212
TI - The effects of a pilot intervention for community-dwelling adults with rheumatoid
arthritis in wuhan, china.
AB - This study examined the effects of a pilot educational intervention program on
knowledge, perceived self-efficacy, and health-related quality of life (HRQoL) of
community-dwelling adults with rheumatoid arthritis (RA). A convenience sample of
16 participants with RA completed the program in Wuhan, China. Data were
collected in face-to-face interviews using questionnaires at baseline, post-test,
and 1 month follow-up. Knowledge scores were significantly increased over time.
Significant differences were found in pain self-efficacy, symptoms self-efficacy,
bodily pain, social functioning, and role emotional functions. Community health
providers should provide educational programs to improve HRQoL for adults with
RA.
PMID- 24350214
TI - A hybrid online intervention for reducing sedentary behavior in obese women.
AB - Sedentary behavior (SB) has emerged as an independent risk factor for
cardiovascular disease and type 2 diabetes. While exercise is known to reduce
these risks, reducing SB through increases in non-structured PA and breaks from
sitting may appeal to obese women who have lower self-efficacy for PA. This study
examined effects of a combined face-to-face and online intervention to reduce SB
in overweight and obese women. A two-group quasi-experimental study was used with
measures taken pre and post. Female volunteers (M age = 58.5, SD = 12.5 years)
were enrolled in the intervention (n = 40) or waitlisted (n = 24). The
intervention, based on the Social Cognitive Theory, combined group sessions with
email messages over 6 weeks. Individualized feedback to support mastery and peer
models of active behaviors were included in the emails. Participants self
monitored PA with a pedometer. Baseline and post measures of PA and SB were
assessed by accelerometer and self-report. Standard measures of height, weight,
and waist circumference were conducted. Repeated measures ANOVA was used for
analyses. Self-reported SB and light PA in the intervention group (I) changed
significantly over time [SB, F(1, 2) = 3.81, p = 0.03, light PA, F(1, 2) = 3.39,
p = 0.04]. Significant Group * Time interactions were found for light PA, F(1,
63) = 5.22, p = 0.03, moderate PA, F(1, 63) = 3.90, p = 0.05, and for waist
circumference, F(1, 63) = 16.0, p = 0.001. The intervention group decreased
significantly while the comparison group was unchanged. Hybrid computer
interventions to reduce SB may provide a non-exercise alternative for increasing
daily PA and potentially reduce waist circumference, a risk factor for type 2
diabetes. Consumer-grade accelerometers may aide improvements to PA and SB and
should be tested as part of future interventions.
PMID- 24350211
TI - Marijuana: current concepts(?).
AB - Marijuana (cannabis) remains a controversial drug in the twenty-first century.
This paper considers current research on use of Cannabis sativa and its
constituents such as the cannabinoids. Topics reviewed include prevalence of
cannabis (pot) use, other drugs consumed with pot, the endocannabinoid system,
use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric
adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence
is difficult and remains mainly based on psychological therapy; current research
on pharmacologic management of problems related to cannabis consumption is also
considered. The potential role of specific cannabinoids for medical benefit will
be revealed as the twenty-first century matures. However, potential dangerous
adverse effects from smoking marijuana are well known and should be clearly
taught to a public that is often confused by a media-driven, though false message
and promise of benign pot consumption.
PMID- 24350215
TI - "I am very, very proud of myself": improving youth activity levels using self
determination theory in program development.
AB - Many adolescents are not meeting recommended levels for physical activity.
Increasing physical activity among urban African American youth is both a
challenge and a public health priority. Most research in community-based
interventions has taken a didactic approach, focusing on skill and knowledge
development alone, with inconclusive results. This 10-week progressive activity
intervention with adolescents in an urban faith community introduced a self
determination theory (SDT) approach with the aim of promoting the adoption of
self-management skills necessary for sustaining activity. Components of SDT
included relatedness, competence, and autonomy. Together with didactics, aligning
activities with participant interests, and using existing social structures for
health message delivery, the approach led to high satisfaction ratings for the
three components of SDT along with improved skills, knowledge, and outcomes in
cardiovascular fitness. Understanding and utilizing approaches that enhance
enjoyment, personal choice, confidence, and social affiliation may lead to more
lasting healthy activity behaviors and attitudes than didactic approaches alone
in this and other adolescent populations. The SDT is reviewed in the context of
this youth intervention.
PMID- 24350216
TI - Analysis of the literature pertaining to the education of public health
professionals.
AB - A well-educated workforce is essential to the infrastructure of a public health
system (1). At a time when global focus on public health is increasing, a severe
shortage of public health professionals is projected (2). A strong educational
framework is thus imperative to ensure the capacity and capability of the
worldwide public health workforce for the future. The education of those who work
in public health is spread across disciplines, subject-specific training programs
and types of academic institutions. In the 2011 report on the Health
Professionals for a New Century, Frenk and Chen comment that, compared to
medicine and nursing, public health has done the least to examine what and how it
teaches (3). This does not bode well for meeting the demands of the public health
workforce for the future. The purpose of the study reported here is to analyze
the state of pedagogy pertaining to the education of the public health workforce
as evidenced by published literature. The focus is on "professionals," defined as
those who have formal education, are self-governing, and can work independently.
PMID- 24350218
TI - Sequential Metastatic Breast Cancer Chemotherapy: Should the Median be the
Message?
AB - BACKGROUND: Counseling and anticipatory guidance of the expected course of
treatment for women newly diagnosed with metastatic breast cancer (MBC) are
difficult due to multiple factors influencing survival following MBC therapy. In
order to better tailor counseling at the onset and through the duration of MBC we
used non-clinical trial data to better characterize real life experience of
sequential MBC treatment. We examined the following aims: (1) What demographic
and tumor characteristics are predictive of survival in MBC? (2) What is the
median duration of each sequential chemotherapy regimen and subsequent survival
of women following each sequence of chemotherapy regimen in MBC? METHODS:
Retrospective study included 792 women diagnosed from January 1999 through
December 2009 at the University of Pittsburgh Cancer Institute Breast Cancer
Program. RESULTS: Median duration of sequential chemotherapy regimen and median
survival from completion of sequence of chemotherapy regimens were relatively
short with a wide range of treatment duration and survival. Characteristics for
poor survival included hormone status, human epidermal growth factor receptor-2
(HER 2/neu) status, and increased number and type of metastatic sites. Women who
took more than the second sequential chemotherapy regimens had no more than
median 3 months of treatment duration and 6 months survival from treatment
termination. DISCUSSION: Median clinical response and survival shorten with
sequential chemotherapy regimen but with wide ranges. The rare clinical response
of the minority should not set the standard for treatment expectations. All
cancer clinicians, including oncology nurses, must ensure that patients are
receiving tailored counseling regarding their specific risks and benefits for
sequential MBC chemotherapy.
PMID- 24350219
TI - Dexamethasone Down-Regulates Expression of Triggering Receptor Expressed on
Myeloid Cells-1: Evidence for a TNFalpha-Related Effect.
AB - OBJECTIVES: To investigate the effect of dexamethasone on triggering receptor
expressed on myeloid cells-1 (TREM-1). METHODS: Wild-type and tumor necrosis
factor (TNF (-/-)) mice were pre-treated with saline, dexamethasone, or
hydrocortisone and exposed to a lethal infection of Pseudomonas aeruginosa.
Mortality and TREM-1 on neutrophil membranes was measured after sacrifice. U937
human monocytic cells were stimulated with lipopolysaccharide (LPS) or heat
killed P. aeruginosa without or with dexamethasone or hydrocortisone, and cell
surface TREM-1 and soluble TREM-1 (sTREM-1) were quantified. Expression of TREM-1
and sTREM-1 was also studied in LPS-stimulated U937 cells incubated in the
absence or presence of TNFalpha or anti-TNFalpha antibody. RESULTS: Pre-treatment
with dexamethasone, but not hydrocortisone, prolonged animal survival. Mice pre
treated with dexamethasone showed decreased expression of TREM-1 on neutrophils.
In U937 cells, LPS or heat-killed P. aeruginosa induced the expression of TREM-1
and the release of sTREM-1. U937 TREM-1 and sTREM-1 were decreased upon addition
of dexamethasone but not hydrocortisone. The suppressive effect of dexamethasone
was enhanced in the presence of exogenous TNFalpha and lost in the presence of
anti-TNFalpha antibody. In TNF (-/-) mice, dexamethasone suppression of mortality
and TREM-1 neutrophil expression was lost. Gene expression of TREM-1 in U937
monocytes was decreased after treatment with dexamethasone. CONCLUSION: TREM
1/sTREM-1 is a novel site of action of dexamethasone. This action is associated
with down-regulation of gene expression and is mediated by TNFalpha.
PMID- 24350217
TI - Dietary patterns and cardiovascular disease-related risks in chinese older
adults.
AB - Studies of Western populations demonstrate a relationship between dietary
patterns and cardiovascular-related risk factors. Similar research regarding
Chinese populations is limited. This study explored the dietary patterns of
Chinese older adults and their association with cardiovascular-related risk
factors, including hypertension, obesity, and metabolic syndrome. Data were
collected using a 34-item Chinese food frequency questionnaire from 750 randomly
selected older adults aged 50-88 who participated in the study in 2012. Factor
analysis revealed four dietary patterns: a "traditional food pattern," consisting
of vegetable, fruit, rice, pork, and fish; a "fast and processed food pattern"
consisting of fast or processed food products, sugar, and confectionery; a
"soybean, grain, and flour food pattern"; and a "dairy, animal liver, and other
animal food pattern." These patterns explained 17.48, 9.52, 5.51, and 4.80% of
the variances in food intake, respectively. This study suggests that specific
dietary patterns are evident in Chinese older adults. Moderate intake of
"traditional Chinese food" is associated with decreased blood pressure and
cholesterol level. A dietary pattern rich in soybeans, grains, potatoes, and
flour is associated with reduced metabolic factors including reduced
triglycerides, fasting glucose, waist circumference, and waist-hip ratio, and a
high level of dairy, animal liver, and other animal intake food pattern is
associated with increased level of Body Mass Index. In conclusion, this study
revealed identifiable dietary patterns among Chinese older adults that are
significantly related to blood pressure and metabolic biomarkers. Further study
using prospective cohort or intervention study should be used to confirm the
association between dietary patterns and blood pressure and metabolic factors.
PMID- 24350220
TI - Short- and long-term mortality in severe sepsis/septic shock in a setting with
low antibiotic resistance: a prospective observational study in a Swedish
university hospital.
AB - BACKGROUND: There is little epidemiologic data on sepsis, particularly in areas
of low antibiotic resistance. Here we report a prospective observational study of
severe sepsis and septic shock in patients admitted to the Intensive Care Unit
(ICU) at Karolinska University Hospital, Sweden. We aimed to evaluate short- and
long-term mortality, and risk factors for sepsis-related death. A second aim was
to investigate patient care in relation to gender. METHODS: One hundred and one
patients with severe sepsis and septic shock, admitted to the ICU between 2005
and 2009, were prospectively enrolled in the study. Defined primary endpoints
were day 28, hospital, and 1-year mortality. Risk factors for sepsis-related
death was evaluated with a multivariate analysis in a pooled analysis with two
previous sepsis cohorts. In the subset of patient admitted to the ICU through the
emergency department (ED), time to clinician evaluation and time to antibiotics
were assessed in relation to gender. RESULTS: In the septic cohort, the day 28,
hospital, and 1-year mortality rates were 19, 29, and 34%, respectively. Ninety
three percent of the patients received adequate antibiotics from the beginning.
Multi-resistant bacteria were only found in three cases. Among the 43 patients
admitted to the ICU through the ED, the median time to antibiotics was 86 min
(interquartile range 52-165), and overall 77% received appropriate antibiotics
within 2 h. Female patients received antibiotics significantly later compared to
male patients (p = 0.047). CONCLUSION: The results demonstrate relatively low
mortality rates among ICU patients with severe sepsis/septic shock, as compared
to reports from outside Scandinavia. Early adequate antibiotic treatment and the
low incidence of resistant isolates may partly explain these findings.
Importantly, a gender difference in time to antibiotic therapy was seen.
PMID- 24350221
TI - Recycling metchnikoff: probiotics, the intestinal microbiome and the quest for
long life.
AB - Over a century ago, Elie Metchnikoff theorized that health could be enhanced and
senility delayed by manipulating the intestinal microbiome with host-friendly
bacteria found in yogurt. His theory flourished for a time, then drifted to the
fringe of medical practice before re-emerging in the mid-1990s as a concept
worthy of mainstream medical attention. Metchnikoff also predicted the existence
of bacterial translocation and anticipated theories linking chronic inflammation
with the pathogenesis of atherosclerosis and other disorders of the aged.
PMID- 24350222
TI - Clinical trial subjects: "panning gold".
PMID- 24350223
TI - Expanded access for a little boy.
PMID- 24350224
TI - When a safety signal appears: do the right thing.
PMID- 24350226
TI - The moral development of the child: an integrated model.
AB - Previous theories of moral development such as those by Piaget and Kohlberg
usually focused on the cognitive or rational aspect, and seldom included the
affective aspect in their construction. The characteristics of the stages of
moral development in the present paper are elaborated with special reference to
psychological needs, altruism and human relationships, and justice reasoning. The
three stages are: (1) Physical Survival, Selfishness, and Obedience, (2) Love
Needs, Reciprocal Altruism, and Instrumental Purpose; and (3) Belongingness
Needs, Primary Group Altruism, and Mutual Interpersonal Expectations. At Stage 1,
a deep and profound attachment to parents, empathy toward the significant others,
and obedience to authorities all contribute to the physical survival of a person
at this stage. People at Stage 2 are self-protective, dominant, exploitative, and
opportunistic. The need to love and to be loved is gratified on the basis of
reciprocal altruism. People at Stage 3 have a strong desire to gratify their
belongingness needs to a primary group. They are willing to sacrifice for the
benefits of the group at great cost. While the psychological needs and altruism
are related to the affective aspect of moral development, the justice reasoning
is related to the cognitive aspect. The proposed theoretical model attempts to
integrate the affective and cognitive aspects of moral development, and
prototypic responses to questions related to hypothetical moral dilemmas are
presented to substantiate the proposed stage structures. It is hypothesized that
the sequence of these three stages is invariant of person and culture.
PMID- 24350225
TI - Electronic cigarettes and vaping: a new challenge in clinical medicine and public
health. A literature review.
AB - Electronic cigarette (e-cigarette) use, or vaping, in the United States and
worldwide is increasing. Their use is highly controversial from scientific,
political, financial, psychological, and sociological ideologies. Given the
controversial nature of e-cigarettes and vaping, how should medical care
providers advise their patients? To effectively face this new challenge, health
care professionals need to become more familiar with the existing literature
concerning e-cigarettes and vaping, especially the scientific literature. Thus,
the aim of this article is to present a review of the scientific evidence-based
primary literature concerning electronic cigarettes and vaping. A search of the
most current literature using the pubmed database dating back to 2008, and using
electronic cigarette(s) or e-cigarette(s) as key words, yielded a total of 66
highly relevant articles. These articles primarily deal with (1) consumer-based
surveys regarding personal views on vaping, (2) chemical analysis of e-cigarette
cartridges, solutions, and mist, (3) nicotine content, delivery, and
pharmacokinetics, and (4) clinical and physiological studies investigating the
effects of acute vaping. When compared to the effects of smoking, the scant
available literature suggests that vaping could be a "harm reduction" alternative
to smoking and a possible means for smoking cessation, at least to the same
degree as other Food and Drug Administration-approved nicotine replacement
therapies. However, it is unclear if vaping e-cigarettes will reduce or increase
nicotine addiction. It is obvious that more rigorous investigations of the acute
and long-term health effects of vaping are required to establish the safety and
efficacy of these devices; especially parallel experiments comparing the
cardiopulmonary effects of vaping to smoking. Only then will the medical
community be able to adequately meet the new challenge e-cigarettes and vaping
present to clinical medicine and public health.
PMID- 24350227
TI - Macau, world capital for gambling: a longitudinal study of a youth program
designed to instill positive values.
AB - This study investigated the effectiveness of a positive youth development program
for Chinese Secondary 3 students in two schools, who had been followed up since
their entry to Secondary 1. A mixed research method was carried out using a pre-
and post-test pre-experimental design and a focus group for the participants. The
subjective outcome evaluations included participants' perceptions of the program,
program instructors, benefits of the program and overall satisfaction, and were
positive. The longitudinal data from the objective outcome evaluation showed some
notable improvements, and the overall effect of the program was also found to be
positive for newcomers in the junior secondary years. The focus group interviews
revealed mostly positive feedback in terms of the students' general impressions
of the program, with the majority of participants perceiving benefits to
themselves from the program. The findings offer positive evidence of the
effectiveness of the program.
PMID- 24350228
TI - Massive open online courses in public health.
AB - Massive open online courses (MOOCs) represent a new and potentially
transformative model for providing educational opportunities to learners not
enrolled in a formal educational program. The authors describe the experience of
developing and offering eight MOOCs on a variety of public health topics.
Existing institutional infrastructure and experience with both for-credit online
education and open educational resources mitigated the institutional risk and
resource requirements. Although learners are able to enroll easily and freely and
do so in large numbers, there is considerable variety in the level of
participation and engagement among enrollees. As a result, comprehensive and
accurate assessment of meaningful learning progress remains a major challenge for
evaluating the effectiveness of MOOCs for providing public health education.
PMID- 24350229
TI - Self-reported juvenile firesetting: results from two national survey datasets.
AB - The main purpose of this study was to address gaps in existing research by
examining the relationship between academic performance and attention problems
with juvenile firesetting. Two datasets from the Achenbach System for Empirically
Based Assessment (ASEBA) were used. The Factor Analysis Dataset (N = 975) was
utilized and results indicated that adolescents who report lower academic
performance are more likely to set fires. Additionally, adolescents who report a
poor attitude toward school are even more likely to set fires. Results also
indicated that attention problems are predictive of self-reported firesetting.
The National Survey Dataset (N = 1158) was analyzed to determine the prevalence
of firesetting in a normative sample and also examine whether these children
reported higher levels of internalizing and externalizing behavior problems. It
was found that 4.5% of adolescents in the generalized sample reported
firesetting. Firesetters reported more internalizing, externalizing, and total
problems than their non-firesetting peers. In this normative sample, firesetters
were found to have lower academic performance and more attention problems.
Limitations include the low overall number of firesetters in each dataset (Factor
Analysis n = 123 and National Survey n = 53) and the inclusion of children who
had been referred for services in the Factor Analysis Dataset.
PMID- 24350231
TI - Examining the Claim that 80-90% of Suicide Cases Had Depression.
PMID- 24350230
TI - Concurrent and simultaneous polydrug use: latent class analysis of an Australian
nationally representative sample of young adults.
AB - BACKGROUND: Alcohol use and illicit drug use peak during young adulthood (around
18-29 years of age), but comparatively little is known about polydrug use in
nationally representative samples of young adults. Drawing on a nationally
representative cross-sectional survey (Australian National Drug Strategy
Household Survey), this study examines polydrug use patterns and associated
psychosocial risk factors among young adults (n = 3,333; age 19-29). METHOD: The
use of a broad range of licit and illicit drugs were examined, including alcohol,
tobacco, cannabis, cocaine, hallucinogens, ecstasy, ketamine, GHB, inhalants,
steroids, barbiturates, meth/amphetamines, heroin, methadone/buprenorphine, other
opiates, painkillers, and tranquilizers/sleeping pills. Latent class analysis was
employed to identify patterns of polydrug use. RESULTS: Polydrug use in this
sample was best described using a 5-class solution. The majority of young adults
predominantly used alcohol only (52.3%), alcohol and tobacco (34.18%). The other
classes were cannabis, ecstasy, and licit drug use (9.4%), cannabis, amphetamine
derivative, and licit drug use (2.8%), and sedative and alcohol use (1.3%). Young
adult males with low education and/or high income were most at risk of polydrug
use. CONCLUSION: Almost half of young adults reported polydrug use, highlighting
the importance of post-high school screening for key risk factors and polydrug
use profiles, and the delivery of early intervention strategies targeting illicit
drugs.
PMID- 24350232
TI - Multiple hypotheses testing procedures in clinical trials and genomic studies.
AB - We review and compare multiple hypothesis testing procedures used in clinical
trials and those in genomic studies. Clinical trials often employ global tests,
which draw an overall conclusion for all the hypotheses, such as SUM test, Two
Step test, Approximate Likelihood Ratio test (ALRT), Intersection-Union Test
(IUT), and MAX test. The SUM and Two-Step tests are most powerful under
homogeneous treatment effects, while the ALRT and MAX test are robust in cases
with non-homogeneous treatment effects. Furthermore, the ALRT is robust to
unequal sample sizes in testing different hypotheses. In genomic studies,
stepwise procedures are used to draw marker-specific conclusions and control
family wise error rate (FWER) or false discovery rate (FDR). FDR refers to the
percent of false positives among all significant results and is preferred over
FWER in screening high-dimensional genomic markers due to its interpretability.
In cases where correlations between test statistics cannot be ignored, Westfall
Young resampling method generates the joint distribution of P-values under the
null and maintains their correlation structure. Finally, the GWAS data from a
clinical trial searching for SNPs associated with nephropathy among Type 1
diabetic patients are used to illustrate various procedures.
PMID- 24350233
TI - Local health department epidemiologic capacity: a stratified cross-sectional
assessment describing the quantity, education, training, and perceived
competencies of epidemiologic staff.
AB - INTRODUCTION: Local health departments (LHDs) must have sufficient numbers of
staff functioning in an epidemiologic role with proper education, training, and
skills to protect the health of communities they serve. This pilot study was
designed to describe the composition, training, and competency level of LHD staff
and examine the hypothesis that potential disparities exist between LHDs serving
different sized populations. MATERIALS AND METHODS: Cross-sectional surveys were
conducted with directors and epidemiologic staff from a sample of 100 LHDs
serving jurisdictions of varied sizes. Questionnaires included inquiries
regarding staff composition, education, training, and measures of competency
modeled on previously conducted studies by the Council of State and Territorial
Epidemiologists. Number of epidemiologic staff, academic degree distribution,
epidemiologic training, and both director and staff confidence in task
competencies were calculated for each LHD size strata. RESULTS: Disparities in
measurements were observed in LHDs serving different sized populations. LHDs
serving small populations reported a smaller average number of epidemiologic
staff than those serving larger jurisdictions. As size of population served
increased, percentages of staff and directors holding bachelors' and masters'
degrees increased, while those holding RN degrees decreased. A higher degree of
perceived competency of staff in most task categories was reported in LHDs
serving larger populations. DISCUSSION: LHDs serving smaller populations reported
fewer epidemiologic staff, therefore might benefit from additional resources.
Differences observed in staff education, training, and competencies suggest that
enhanced epidemiologic training might be particularly needed in LHDs serving
smaller populations. RESULTS can be used as a baseline for future research aimed
at identifying areas where training and personnel resources might be particularly
needed to increase the capabilities of LHDs.
PMID- 24350234
TI - The Association between Trust in Health Care Providers and Medication Adherence
among Black Women with Hypertension.
AB - BACKGROUND: Black women have the highest prevalence of hypertension in the world.
Reasons for this disparity are poorly understood. The historical legacy of
medical maltreatment of Blacks in the U.S. provides some insight into distrust in
the medical profession, refusal of treatment, and poor adherence to treatment
regimens. METHODS: Black women (N = 80) who were prescribed antihypertensive
medications were recruited from urban communities in North Carolina. Study
participants completed the Trust in Physician and Hill-Bone Compliance to High
Blood Pressure Therapy questionnaires. An exact discrete-event model was used to
examine the relationship between trust and medication adherence. RESULTS: Mean
age of study participants was 48 +/- 9.2 years. The majority of participants
(67%) were actively employed and 30% had incomes at or below the federal poverty
level. Increasing levels of trust in the health care provider was independently
associated with greater medication adherence (P Trend = 0.015). CONCLUSION: Black
women with hypertension who trusted their health care providers were more likely
to be adherent with their prescribed antihypertensive medications than those who
did not trust their health care providers. Findings suggest that trusting
relationships between Black women and health care providers are important to
decreasing disparate rates of hypertension.
PMID- 24350235
TI - Hypertension Awareness and Associated Factors among Older Chinese Adults.
AB - Hypertension is one of the most preventable chronic conditions. Improving
hypertension awareness is a critical first step to reducing morbidity and
mortality from hypertension in the elderly, yet the factors associated with
hypertension awareness in China are poorly understood. The objective of this
paper is to examine the extent to which older Chinese adults are aware of their
hypertension, and factors associated with this awareness. We included 2404 adults
aged 60 years or older clinically identified as hypertensive from panel data
surveyed in 1997, 2000, 2004, and 2006 as part of the China Health and Nutrition
Survey. Comparing this data with respondents' self-reported diagnosis of
hypertension enabled us to characterize hypertension awareness. Covariates
included socio-demographic, health status, functional disability, and behavioral
factors. Generalized estimating equations were used to identify factors for
hypertension awareness. We found 22.9% in 1997 and 42.7% in 2006 of study
participants were aware of their hypertensive status. Lower awareness was found
among those who lived in rural areas [odds ratio (OR) = 0.64, 95% Confidence
Interval (CI), 0.47-0.88]. Higher awareness was noted for persons who were aware
of their hypertensive status in a previous survey wave (OR = 7.43, 95% CI, 5.45
10.13), had high income (OR = 1.55, 95% CI, 1.05-2.28), had stage two
hypertension (OR = 2.28, 95% CI, 1.69-3.06), had acute condition (OR = 2.54, 95%
CI, 1.89-3.42), and had greater activities of daily living limitations (OR =
1.24, 95% CI, 1.08-1.43). Studying dynamics of hypertension awareness can help
inform both clinical and public health approaches to improve healthcare.
PMID- 24350236
TI - What is Normal? The Impact of Psychiatric Classification on Mental Health
Practice and Research.
PMID- 24350237
TI - Comparing Adult Males and Females in the United States to Examine the Association
between Body Mass Index and Frequent Mental Distress: An Analysis of Data from
BRFSS 2011.
AB - Background. There is conflicting evidence regarding the association of body mass
index (BMI) with mental distress. Studies have focused on different dimensions of
mental health and used different definitions and many of them have not controlled
for confounding factors. The aim of this study was to examine the relationship
between frequent mental distress (FMD) and BMI among adults in the United States,
with special emphasis on gender differences. Methods. Data from the Behavioral
Risk Factor Surveillance System (BRFSS) for the year 2011 were used in logistic
regression models to predict FMD, defined as having 14 or more days of poor
mental health in the previous month. Sociodemographic factors, tobacco and
alcohol use, diet and physical activity, and number of chronic diseases were
controlled for. Results. 11.95% (n = 53,715) of the participants with valid
responses (n = 496,702) had FMD. The adjusted ORs of having FMD among
underweight, overweight, and obese females were 1.13 (95% CI: 1.10, 1.60), 1.10
(95% CI: 1.03, 1.19), and 1.21 (95% CI: 1.13, 1.31), respectively, but they were
not statistically significant for males. Conclusions. These findings suggest a
relationship between BMI and FMD, independent of other variables. It may be
useful to explore longitudinal trend in this association.
PMID- 24350238
TI - Differential Expression of Myogenic Regulatory Factor Genes in the Skeletal
Muscles of Tambaqui Colossoma macropomum (Cuvier 1818) from Amazonian Black and
Clear Water.
AB - Hypothesizing that the Amazonian water system differences would affect the
expression of muscle growth-related genes in juvenile tambaqui Colossoma
macropomum (Cuvier 1818), this study aimed to analyze the morphometric data and
expression of myogenic regulatory factors (MRFs) in the white and red muscle from
tambaqui obtained from clear and black Amazonian water systems. All of the MRF
transcript levels (myod, myf5, myogenin, and mrf4) were significantly lower in
the red muscle from black water fish in comparison to clear water fish. However,
in white muscle, only the myod transcript level was significantly decreased in
the black water tambaqui. The changes in MRFs gene expression in muscle fibers of
tambaqui from black water system provide relevant information about the
environmental influence as that of water systems on gene expression of muscle
growth related genes in the C. macropomum. Our results showed that the physical
and chemical water characteristics change the expression of genes that promote
muscle growth, and these results may be also widely applicable to future projects
that aim to enhance muscle growth in fish that are of substantial interest to the
aquaculture.
PMID- 24350239
TI - Microarray analysis of transcriptome of medulla identifies potential biomarkers
for Parkinson's disease.
AB - To complement the molecular pathways contributing to Parkinson's disease (PD) and
identify potential biomarkers, gene expression profiles of two regions of the
medulla were compared between PD patients and control. GSE19587 containing two
groups of gene expression profiles [6 dorsal motor nucleus of the vagus (DMNV)
samples from PD patients and 5 from controls, 6 inferior olivary nucleus (ION)
samples from PD patients and 5 from controls] was downloaded from Gene Expression
Omnibus. As a result, a total of 1569 and 1647 differentially expressed genes
(DEGs) were, respectively, screened in DMNV and ION with limma package of R. The
functional enrichment analysis by DAVID server (the Database for Annotation,
Visualization and Integrated Discovery) indicated that the above DEGs may be
involved in the following processes, such as regulation of cell proliferation,
positive regulation of macromolecule metabolic process, and regulation of
apoptosis. Further analysis showed that there were 365 common DEGs presented in
both regions (DMNV and ION), which may be further regulated by eight clusters of
microRNAs retrieved with WebGestalt. The genes in the common DEGs-miRNAs
regulatory network were enriched in regulation of apoptosis process via DAVID
analysis. These findings could not only advance the understandings about the
pathogenesis of PD, but also suggest potential biomarkers for this disease.
PMID- 24350240
TI - Why is diabetes mellitus a risk factor for contrast-induced nephropathy?
AB - Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute
kidney injury, as the usage of contrast media for imaging and intravascular
intervention keeps expanding. Diabetes is an important predisposing factor for
CIN, particularly in patients with renal functional impairment. Renal hypoxia,
combined with the generation of reactive oxygen species, plays a central role in
the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to
intensified hypoxic and oxidative stress following the administration of contrast
media. The pathophysiology of this vulnerability is complex and involves various
mechanisms, including a priori enhanced tubular transport activity, oxygen
consumption, and the generation of reactive oxygen species. The regulation of
vascular tone and peritubular blood flow may also be altered, particularly due to
defective nitrovasodilation, enhanced endothelin production, and a particular
hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro-
and macrovascular diseases and chronic tubulointerstitial changes further
compromise regional oxygen delivery, and renal antioxidant capacity might be
hampered. A better understanding of these mechanisms and their control in the
diabetic patient may initiate novel strategies in the prevention of contrast
nephropathy in these susceptible patients.
PMID- 24350241
TI - Prediction of drugs target groups based on ChEBI ontology.
AB - Most drugs have beneficial as well as adverse effects and exert their biological
functions by adjusting and altering the functions of their target proteins. Thus,
knowledge of drugs target proteins is essential for the improvement of
therapeutic effects and mitigation of undesirable side effects. In the study, we
proposed a novel prediction method based on drug/compound ontology information
extracted from ChEBI to identify drugs target groups from which the kind of
functions of a drug may be deduced. By collecting data in KEGG, a benchmark
dataset consisting of 876 drugs, categorized into four target groups, was
constructed. To evaluate the method more thoroughly, the benchmark dataset was
divided into a training dataset and an independent test dataset. It is observed
by jackknife test that the overall prediction accuracy on the training dataset
was 83.12%, while it was 87.50% on the test dataset-the predictor exhibited an
excellent generalization. The good performance of the method indicates that the
ontology information of the drugs contains rich information about their target
groups, and the study may become an inspiration to solve the problems of this
sort and bridge the gap between ChEBI ontology and drugs target groups.
PMID- 24350242
TI - New trends in biotechnological processes to increase the environmental
protection.
PMID- 24350243
TI - Topical promethazine side effects: our experience and review of the literature.
AB - Promethazine hydrochloride is a first-generation H1 receptor antagonist,
antihistamine, and antiemetic medication that can also have strong sedative
effects. The apparent ability of topical H1r/2r antagonists to target epidermal
H1/2r was translated into increased efficacy in the treatment of inflammatory
dermatoses, likely due to decreased inflammation and enhanced barrier function.
PMID- 24350244
TI - Robotic technologies and rehabilitation: new tools for stroke patients' therapy.
AB - INTRODUCTION: The role of robotics in poststroke patients' rehabilitation has
been investigated intensively. This paper presents the state-of-the-art and the
possible future role of robotics in poststroke rehabilitation, for both upper and
lower limbs. MATERIALS AND METHODS: We performed a comprehensive search of
PubMed, Cochrane, and PeDRO databases using as keywords "robot AND stroke AND
rehabilitation." RESULTS AND DISCUSSION: In upper limb robotic rehabilitation,
training seems to improve arm function in activities of daily living. In
addition, electromechanical gait training after stroke seems to be effective. It
is still unclear whether robot-assisted arm training may improve muscle strength,
and which electromechanical gait-training device may be the most effective for
walking training implementation. CONCLUSIONS: In the field of robotic
technologies for stroke patients' rehabilitation we identified currently relevant
growing points and areas timely for developing research. Among the growing points
there is the development of new easily transportable, wearable devices that could
improve rehabilitation also after discharge, in an outpatient or home-based
setting. For developing research, efforts are being made to establish the ideal
type of treatment, the length and amount of training protocol, and the patient's
characteristics to be successfully enrolled to this treatment.
PMID- 24350245
TI - Pyrolytic and kinetic analysis of two coastal plant species: Artemisia annua and
Chenopodium glaucum.
AB - The large amount of coastal plant species available makes them ideal candidates
for energy production. In this study, thermogravimetric analysis was used to
evaluate the fuel properties of two coastal plant species, and the distributed
activation energy model (DAEM) was employed in kinetic analysis. The major mass
loss due to devolatilization started at 154 and 162 degrees C at the heating rate
of 10 degrees C min(-1) for Artemisia annua and Chenopodium glaucum,
respectively. The results showed that the average activation energies of
Artemisia annua and Chenopodium glaucum were 169.69 and 170.48 kJ mol(-1),
respectively. Furthermore, the activation energy changed while the conversion
rate increased, and the frequency factor k 0 decreased greatly while the
activation energy decreased. The results also indicated that the devolatilization
of the two coastal plant species underwent a set of first-order reactions and
could be expressed by the DAEM. Additionally, a simplified mathematical model was
proposed to facilitate the prediction of devolatilization curves.
PMID- 24350247
TI - Clinical application of vascular regenerative therapy for peripheral artery
disease.
AB - Prognosis of peripheral artery disease (PAD), especially critical limb ischemia,
is very poor despite the development of endovascular therapy and bypass surgery.
Many patients result in leg amputation and, therefore, vascular regenerative
therapy is expected in this field. Gene therapy using vascular endothelial growth
factor is the first step of vascular regenerative therapy, but did not confirm
effectiveness in a large-scale randomized comparative study. Based on animal
experiments, bone marrow mononuclear cells (MNCs), peripheral blood MNCs were
used as the cell source for regenerative therapy. Those cells were confirmed to
be effective to decrease rest pain and ulcer size, but its effect was not fully
satisfied. Mesenchymal stem cells (MSCs) are expected as an effective cell source
for vascular regeneration and clinical studies are ongoing, because the cells are
able to differentiate into various cell types and produce a significant amount of
vascular growth factors. Of vascular regeneration therapy, peripheral MNCs and
bone marrow MNCs were recognized as advanced medical technology but do not attain
to the standard therapy. However, clinical use of MSCs have already started, and
induced pluripotent stem cells are surely promising tool for vascular
regeneration therapy although further basic studies are required for clinical
application.
PMID- 24350248
TI - Ovarian stimulation affects the population of mouse uterine NK cells at early
pregnancy.
AB - The aim of this study was to determine the influence of ovarian stimulation on
endometrial mouse NK cell population. For superovulation, the female adult NMRI
mice were injected i.p. with 10 IU of the pregnant mare serum gonadotropin
followed 48 h later by an i.p. injection of 10 IU human chorionic gonadotropin
hormone. Ovarian stimulated and nonstimulated mice were mated with fertile male.
The presence of vaginal plug proved natural pregnancy, and this day was
considered as day one of pregnancy. Tissue samples were prepared from the uterine
horn and spleen of both groups of study on 7th day of pregnancy. Serum estradiol
17beta and progesterone were measured at the same time. The tissue cryosections
were prepared and double stained for CD 161 and CD3 markers, and NK cells
population was analyzed. Relative frequency of NK cells was significantly lower
in stroma and myometrium in hyperstimulated mice compared with the control group.
However, no difference was seen in percentage of NK cells in spleen. The ovarian
stimulation influences the proportion of uterine NK cells and may affect the
embryo implantation.
PMID- 24350246
TI - Pattern recognition receptors and cytokines in Mycobacterium tuberculosis
infection--the double-edged sword?
AB - Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (Mtb),
remains a major cause of human death worldwide. Innate immunity provides host
defense against Mtb. Phagocytosis, characterized by recognition of Mtb by
macrophages and dendritic cells (DCs), is the first step of the innate immune
defense mechanism. The recognition of Mtb is mediated by pattern recognition
receptors (PRRs), expressed on innate immune cells, including toll-like receptors
(TLRs), complement receptors, nucleotide oligomerization domain like receptors,
dendritic cell-specific intercellular adhesion molecule grabbing nonintegrin (DC
SIGN), mannose receptors, CD14 receptors, scavenger receptors, and FCgamma
receptors. Interaction of mycobacterial ligands with PRRs leads macrophages and
DCs to secrete selected cytokines, which in turn induce interferon-gamma-
(IFNgamma-) dominated immunity. IFNgamma and other cytokines like tumor necrosis
factor-alpha (TNFalpha) regulate mycobacterial growth, granuloma formation, and
initiation of the adaptive immune response to Mtb and finally provide protection
to the host. However, Mtb can evade destruction by antimicrobial defense
mechanisms of the innate immune system as some components of the system may
promote survival of the bacteria in these cells and facilitate pathogenesis.
Thus, although innate immunity components generally play a protective role
against Mtb, they may also facilitate Mtb survival. The involvement of selected
PRRs and cytokines on these seemingly contradictory roles is discussed.
PMID- 24350249
TI - Prostaglandin analogous and antioxidant activity mediated gastroprotective action
of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract against
chemically induced gastric ulcers in rats.
AB - The present study was conducted to evaluate the antiulcerogenic effect and
recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br.
flowers. T. divaricata flower methanolic extract (TDFME) was screened for
antiulcer activity versus aspirin and ethanol induced gastric ulcers at three
doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides
histopathological examination, seven parameters, that is, ulcer index, total
protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and
superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS
analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS)
analysis of crude TDFME were carried out in an attempt to identify known
phytochemicals present in the extract on the basis of m/z value. The results
revealed a significant increase in the levels of catalase, superoxide dismutase,
mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer
index, the levels of total protein, and malondialdehyde. Histopathological
observations also demonstrated the protective effect. Though all the doses of
TDFME exhibited gastroprotective function, higher doses were found to be more
effective. Mass spectral analysis gave a few characteristic m/z values suggesting
the presence of a few known indole alkaloids, while HPLC profiling highlighted
the complexity of the extract. TDFME was found to exhibit its gastroprotective
effect through antioxidant mechanism and by enhancing the production of gastric
mucous.
PMID- 24350250
TI - Extraction and separation of fucoidan from Laminaria japonica with chitosan as
extractant.
AB - Herein the extraction method of fucoidan from Laminaria japonica is reported.
Firstly, chitosan, chitosan-N-2-hydroxypropyl trimethyl ammonium chloride (HACC),
and hexadecyltrimethylammonium bromide (CPAB) were used to extract the fucoidan.
The results showed that chitosan was the optimal extractant compared with the
other two extractants. After extraction, different aqueous solutions, including
NaCl, KCl, and HCl (pH2), were used to separate fucoidan from chitosan-fucoidan
complex. The results showed that the separation ability of NaCl was slightly
higher than that of KCl. Moreover, the price of NaCl is lower than that of KCl.
Given the quality-price rate, NaCl solution was chosen as the separation
solution. Thirdly, the concentration and ratio of NaCl solution : sediment
influence the separation of fucoidan from chitosan-fucoidan complex. The results
showed that the optimal separation conditions include 4 mol/L NaCl solution with
the ratio of NaCl solution to sediment at 30 : 1. Fucoidan content was found to
be affected by different separation time. Fucoidan content increased with the
increase of separation time, and the optimal separation time was 6 h. Compared
with traditional alkali extraction method, this method not only reduces the usage
of alkali and acid and alleviate environment pollution, but also has the
comparable extraction yield of fucoidan. It is a potential method for extraction
of fucoidan.
PMID- 24350251
TI - Modification of a rodent hindlimb model of secondary lymphedema: surgical
radicality versus radiotherapeutic ablation.
AB - Secondary lymphedema is an intractable disease mainly caused by damage of the
lymphatic system during surgery, yet studies are limited by the lack of suitable
animal models. The purpose of this study was to create an improved model of
secondary lymphedema in the hindlimbs of rodents with sustained effects and able
to mimic human lymphedema. This was achieved by combining previously reported
surgical methods and radiation to induce chronic lymphedema. Despite more radical
surgical destruction of superficial and deep lymphatic vessels, surgery alone was
not enough to sustain increased hindlimb volume. Radiotherapy was necessary to
prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but
hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The
applicability of this model for studies of therapeutic lymphangiogenesis was
subsequently tested by injecting muscle-derived stem cells previously cocultured
with the supernatant of human lymphatic endothelial cells in vitro. There was a
tendency for increased lymphatic flow which significantly increased lymphatic
vessel formation after cell injection, but attenuation of hindlimb volume was not
observed. These results suggest that further refinement of the rodent hindlimb
model is needed by titration of adequate radiation dosage, while stem cell
lymphangiogenesis seems to be a promising approach.
PMID- 24350252
TI - Translational biomedical informatics and computational systems medicine.
PMID- 24350253
TI - Association of genetic variants of BMP4 with type 2 diabetes mellitus and
clinical traits in a Chinese Han population.
AB - BMP4 is one of the transforming growth factor- beta superfamily, which can
participate in adipogenesis. Gene encoding BMP4 is acknowledged as a convincing
candidate that may contribute to both glucose and lipid metabolism. In this
paper, we aimed to test the impacts of BMP4 variants on type 2 diabetes in a
large sample of Chinese population. We genotyped 10 tagging single nucleotide
polymorphisms within the BMP4 region in 6822 participants and acquired detailed
clinical investigations and biochemistry measurements. We found that BMP4
rs8014363 showed nominal association towards type 2 diabetes, with the T allele
conferring a high risk of type 2 diabetes (OR = 1.108, 95%CI 0.999-1.229, P =
0.051 for allele; OR = 1.110, 95%CI 1.000-1.231, P = 0.050 for genotype), but it
was no longer statistically significant after adjusting for multiple testing
(empirical P = 0.3689 for allele based on 10,000 permutations). Moreover, we
observed a significant association of rs8014363 with triglyceride level and a
trend towards association with high-density lipoprotein cholesterol after
adjusting for age, gender, and BMI (P = 0.035 and 0.068, resp.). Our data
suggested that the genetic variants of BMP4 may not play a dominant role in
glucose metabolism in Chinese Han population, but a minor effect cannot be
ignored.
PMID- 24350254
TI - Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs
endothelial corneal dystrophy.
AB - Oxidative stress may play a role in the pathogenesis of keratoconus (KC) and
Fuchs endothelial corneal dystrophy (FECD). Iron may promote the stress by the
Fenton reaction, so its homeostasis should be strictly controlled. Transferrin is
essential for iron homeostasis because it transports iron from plasma into cells.
The malfunction of transferrin, which may be caused by variation in its gene (TF)
variation, may contribute to oxidative stress and change KC and FECD risk. To
verify this hypothesis we investigated the association between three
polymorphisms of the TF gene, g.3296G>A (rs8177178), g.3481A>G (rs8177179), and
c.-2G>A (rs1130459), and KC and FECD occurrence. Genotyping was performed in
blood lymphocytes in 216 patients with KC, 130 patients with FECD and 228
controls by PCR-RFLP. We studied also the influence of other risk factors. The
A/A genotype and the A allele of the g.3296G>A polymorphism were associated with
KC occurrence, while the G allele was negatively correlated with it. We observed
a decrease in KC occurrence associated with the A/G genotype of the g.3481A>G
polymorphism. We did not find any association between the c.-2G>A polymorphism
and KC. No association was found between all three polymorphisms and FECD
occurrence.
PMID- 24350255
TI - Grappling the high altitude for safe edible bamboo shoots with rich nutritional
attributes and escaping cyanogenic toxicity.
AB - Consumption of bamboo species with high level of total cyanogenic content (TCC)
in Asia by many ethnic groups is significantly associated with food poisoning and
occasionally Konzo (a neurological disorder). Adequate characterization of edible
bamboo species with low level of TCC and high nutritious attributes is required
for consumer's safety as well as for the conservation of the gene pool. Here, we
employed morphological descriptors, atomic absorption spectrophotometer, RAPD,
and trnL-F intergenic spacer to characterize 15 indigenous edible bamboo species
of north-east India. The study indicates that morphologically and genetically
evolved edible bamboo species having large and robust bamboo-shoot texture and
growing at low altitude contain high level of TCC, low antioxidant properties,
and low levels of beneficial macronutrients and micronutrients. Importantly,
Dendrocalamus species are shown to be rich in TCC irrespective of the growing
altitude while Bambusa species are found to have moderate level of TCC. The
findings clearly demonstrated that Chimonobambusa callosa growing at high
altitude represents safe edible bamboo species with nutritious attributes.
PMID- 24350256
TI - Role of stenting for intracranial atherosclerosis in the post-SAMMPRIS era.
AB - Introduction. The initial promise of endovascular stenting for the treatment of
intracranial atherosclerotic disease (ICAD) has been tempered by the results of
the SAMMPRIS trial which demonstrated better outcomes with medical management
compared to stenting for symptomatic ICAD. We review post-SAMMPRIS ICAD stenting
outcomes. Methods. A comprehensive literature search was performed using PubMed
to identify all ICAD stenting series published after the SAMMPRIS in September
2011. The type and design of the stent, number of patients and lesions, inclusion
criteria, and clinical and angiographic outcomes were noted. Results. From
October 2011 to August 2013, 19 ICAD stenting series were identified describing
the interventional outcomes for 2,196 patients with 2,314 lesions. Of the 38
different stents used, 87% were balloon-expandable stents (BESs) and 13% were
self-expanding stents. The median minimum stenosis was 50%. The median rates of
technical success rate, postprocedural ischemic events, and symptomatic in-stent
restenosis (ISR) were 98% (range 87-100%), 9.4% (range 0-25%), and 2.7% (range 0
11.1%), respectively. The median follow-up durations were one to 67 months.
Conclusions. The management of severe ICAD remains controversial. Future trials
are needed to define the optimal patient, lesion, and stent characteristics which
will portend the best outcomes with intervention.
PMID- 24350258
TI - Changes in maternal serum transforming growth factor beta-1 during pregnancy: a
cross-sectional study.
AB - Changes in circulating levels of maternal serum transforming growth factor beta-1
(TGF-beta1), collected from 98 women (AGA) at different gestational ages (10-38
weeks) were measured and comparisons were made between levels in pregnant and
nonpregnant controls and also between 10 women with small-for-gestational age
(SGA) and 7 with appropriate-for-gestational age (AGA) fetuses. Maternal serum
TGF-beta1 levels at all stages of pregnancy were higher than those in normal
healthy nonpregnant adults. The mean TGF-beta1 levels in SGA pregnancies at 34
week gestation (32.5 + 3.2 ng/mL) were significantly less than those in AGA
pregnancies (39.2 + 9.8 ng/mL) while at 38-week gestation, the levels were
similar in the two groups (36.04 + 4.3 versus 36.7 + 7.0 ng/mL). This
differential change in TGF-beta1 levels is probably an important modulating
factor in the aetiopathogenesis of abnormal intrauterine fetal growth.
PMID- 24350257
TI - Dual inhibiting senescence and epithelial-to-mesenchymal transition by
erythropoietin preserve tubular epithelial cell regeneration and ameliorate renal
fibrosis in unilateral ureteral obstruction.
AB - This study aims to investigate the renoprotective effect of recombinant human
erythropoietin (rhEPO) treatment could preserve tubular epithelial cell
regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced
senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or
sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment
and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for
histopathological and immunohistochemical study. The expression of S100A4, TGF
beta1, BMP-7, Smad2/3, Smad1/5/8, and p16(INK4a) was determined by western blot
and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and
interstitial fibrosis within 3 to 14 days. An increase in TGF-beta1, Smad2/3,
S100A4, and p16(INK4a) expression and a decrease in BMP-7 and Smad1/5/8
expression were observed in the obstructed kidneys. p16(INK4a) was positively
correlated with TGF-beta1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8
in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF
beta, Smad2/3, S100A4, and p16(INK4a) and preserved the downregulation of BMP-7
and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle
treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by
modulating senescence and EMT which could be a part of therapeutic option in
patients with chronic kidney disease.
PMID- 24350260
TI - Microbial removal of the pharmaceutical compounds Ibuprofen and diclofenac from
wastewater.
AB - Studies on the occurrence of pharmaceuticals show that the widely used
pharmaceuticals ibuprofen and diclofenac are present in relevant concentrations
in the environment. A pilot plant treating hospital wastewater with relevant
concentrations of these pharmaceuticals was evaluated for its performance to
reduce the concentration of the pharmaceuticals. Ibuprofen was completely
removed, whereas diclofenac yielded a residual concentration, showing the
necessity of posttreatment to remove diclofenac, for example, activated carbon.
Successively, detailed laboratory experiments with activated sludge from the same
wastewater treatment plant showed bioremediation potential in the treatment
plant. The biological degradation pathway was studied and showed a mineralisation
of ibuprofen and degradation of diclofenac. The present microbes were further
studied in laboratory experiments, and DGGE analyses showed the enrichment and
isolation of highly purified cultures that degraded either ibuprofen or
diclofenac. This research illuminates the importance of the involved bacteria for
the effectiveness of the removal of pharmaceuticals in a wastewater treatment
plant. A complete removal of pharmaceuticals from wastewater will stimulate water
reuse, addressing the worldwide increasing demand for clean and safe fresh water.
PMID- 24350259
TI - Effects of DL-homocysteine thiolactone on cardiac contractility, coronary flow,
and oxidative stress markers in the isolated rat heart: the role of different
gasotransmitters.
AB - Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL
Hcy TLHC) on vascular function and the possible role of oxidative stress in these
mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC
alone and in combination with specific inhibitors of important gasotransmitters,
such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and
oxidative stress markers in an isolated rat heart. The hearts were retrogradely
perfused according to the Langendorff technique at a 70 cm H2O and administered
10 MUM DL-Hcy TLHC alone or in combination with 30 MUM L-NAME, 10 MUM DL-PAG,
or 10 MUM PPR IX. The following parameters were measured: dp/dt max, dp/dt min,
SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured
spectrophotometrically in coronary effluent through TBARS, NO2, O2(-), and H2O2
concentrations. The administration of DL-Hcy TLHC alone decreased dp/dt max,
SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with
L-NAME decreased CF, O2(-), H2O2, and TBARS. The administration of DL-Hcy TLHC
with DL-PAG significantly increased dp/dt max but decreased DLVP, CF, and TBARS.
Administration of DL-Hcy TLHC with PPR IX caused a decrease in dp/dt max, SLVP,
HR, CF, and TBARS.
PMID- 24350261
TI - Practical considerations and challenges involved in surfactant enhanced
bioremediation of oil.
AB - Surfactant enhanced bioremediation (SEB) of oil is an approach adopted to
overcome the bioavailability constraints encountered in biotransformation of
nonaqueous phase liquid (NAPL) pollutants. Fuel oils contain n-alkanes and other
aliphatic hydrocarbons, monoaromatics, and polynuclear aromatic hydrocarbons
(PAHs). Although hydrocarbon degrading cultures are abundant in nature, complete
biodegradation of oil is rarely achieved even under favorable environmental
conditions due to the structural complexity of oil and culture specificities.
Moreover, the interaction among cultures in a consortium, substrate interaction
effects during the degradation and ability of specific cultures to alter the
bioavailability of oil invariably affect the process. Although SEB has the
potential to increase the degradation rate of oil and its constituents, there are
numerous challenges in the successful application of this technology. Success is
dependent on the choice of appropriate surfactant type and dose since the
surfactant-hydrocarbon-microorganism interaction may be unique to each scenario.
Surfactants not only enhance the uptake of constituents through micellar
solubilization and emulsification but can also alter microbial cell surface
characteristics. Moreover, hydrocarbons partitioned in micelles may not be
readily bioavailable depending on the microorganism-surfactant interactions.
Surfactant toxicity and inherent biodegradability of surfactants may pose
additional challenges as discussed in this review.
PMID- 24350262
TI - Physiotherapists have accurate expectations of their patients' future health
related quality of life after first assessment in a subacute rehabilitation
setting.
AB - BACKGROUND: Expectations held by health professionals and their patients are
likely to affect treatment choices in subacute inpatient rehabilitation settings
for older adults. There is a scarcity of empirical evidence evaluating whether
health professionals expectations of the quality of their patients' future health
states are accurate. METHODS: A prospective longitudinal cohort investigation was
implemented to examine agreement (kappa coefficients, exact agreement, limits-of
agreement, and intraclass-correlation coefficients) between physiotherapists' (n
= 23) prediction of patients' discharge health-related quality of life (reported
on the EQ-5D-3L) and the actual health-related quality of life self-reported by
patients (n = 272) at their discharge assessment (using the EQ-5D-3L). The mini
mental state examination was used as an indicator of patients' cognitive ability.
RESULTS: Overall, 232 (85%) patients had all assessment data completed and were
included in analysis. Kappa coefficients (exact agreement) ranged between 0.37
0.57 (58%-83%) across EQ-5D-3L domains in the lower cognition group and 0.53-0.68
(81%-85%) in the better cognition group. CONCLUSIONS: Physiotherapists in this
subacute rehabilitation setting predicted their patients' discharge health
related quality of life with substantial accuracy. Physiotherapists are likely
able to provide their patients with sound information regarding potential
recovery and health-related quality of life on discharge. The prediction accuracy
was higher among patients with better cognition than patients with poorer
cognition.
PMID- 24350263
TI - Speciation in Thaparocleidus (Monogenea: Dactylogyridae) parasitizing Asian
Pangasiid catfishes.
AB - The phylogeny of monogeneans of the genus Thaparocleidus that parasitize the
gills of Pangasiidae in Borneo and Sumatra was inferred from molecular data to
investigate parasite speciation. The phylogeny of the Pangasiidae was also
reconstructed in order to investigate host-parasite coevolutionary history. The
monophyly of Thaparocleidus parasitizing Pangasiidae was confirmed. Low
intraspecies molecular variability was observed in three Thaparocleidus species
collected from geographically distant localities. However, a high intraspecies
molecular variability was observed in two Thaparocleidus species suggesting that
these species represent a complex of species highly similar in morphology.
Distance-based and tree-based methods revealed a significant global fit between
parasite and host phylogenies. Parasite duplication (i.e., intrahost speciation)
was recognized as the most common event in Thaparocleidus, while the numbers of
cospeciation and host switches were lower and similar to each other. When
collapsing nodes correspond to duplication cases, our results suggest host
switches in the Thaparocleidus-Pangasiidae system precluding congruence between
host and parasite trees. We found that the morphometric variability of the
parasite attachment organ is not linked to phylogeny, suggesting that the
attachment organ is under adaptive constraint. We showed that haptor morphometry
is linked to host specificity, whereby nonspecific parasites display higher
morphometric variability than specialists.
PMID- 24350264
TI - Regulation of PKC autophosphorylation by calponin in contractile vascular smooth
muscle tissue.
AB - Protein kinase C (PKC) is a key enzyme involved in agonist-induced smooth muscle
contraction. In some cases, regulatory phosphorylation of PKC is required for
full activation of the enzyme. However, this issue has largely been ignored with
respect to PKC-dependent regulation of contractile vascular smooth muscle (VSM)
contractility. The first event in PKC regulation is a transphosphorylation by PDK
at a conserved threonine in the activation loop of PKC, followed by the
subsequent autophosphorylation at the turn motif and hydrophobic motif sites. In
the present study, we determined whether phosphorylation of PKC is a regulated
process in VSM and also investigated a potential role of calponin in the
regulation of PKC. We found that calponin increases the level of in vitro
PKCalpha phosphorylation at the PDK and hydrophobic sites, but not the turn motif
site. In vascular tissues, phosphorylation of the PKC hydrophobic site, but not
turn motif site, as well as phosphorylation of PDK at S241 increased in response
to phenylephrine. Calponin knockdown inhibits autophosphorylation of cellular PKC
in response to phenylephrine, confirming results with recombinant PKC. Thus these
results show that autophosphorylation of PKC is regulated in dVSM and calponin is
necessary for autophosphorylation of PKC in VSM.
PMID- 24350265
TI - A biomechanical research of growth control of spine by shape memory alloy
staples.
AB - Shape memory alloy (SMA) staples in nickel titanium with shape memory effect are
effective for spinal growth control. This study was designed to evaluate the
biomechanical properties of the staples and observe the stability of the fixed
segments spine after the staples were implanted. According to the vertical
distance of the vertebrae, SMA staples of 5, 6.5, and 8 mm were designed. The
recovery stress of 24 SMA staples in three groups was measured. The pullout
strength of SMA staples and stainless steel staples in each functional spinal
unit was measured. Each of the six fresh specimens was divided into three
conditions: normal, single staple, and double staples. Under each condition, the
angle and torque of spinal movements in six directions were tested. Results show
that the differences in recovery stress and maximum pullout strength between
groups were statistically significant. In left and right bending, flextion, and
extention, the stability of spine was decreased in conditions of single staple
and double staples. Biomechanical function of SMA staples was superior to
stainless steel staple. SMA staples have the function of hemiepiphyseal
compression and kyphosis and scoliosis model of thoracic vertebrae in goat could
be successfully created by the fusionless technique.
PMID- 24350266
TI - What would be the most appropriate alpha/beta ratio in the setting of
stereotactic body radiation therapy for early stage non-small cell lung cancer.
AB - We hypothesize that the correlation between the radiation dose expressed as the
biologically effective dose (BED) and the clinical endpoints will correlate
better as the value of the alpha/beta ratio is increased to >10 Gy, which
theoretically minimizes the overestimation of the dose potency associated with
the linear quadratic (LQ) formula in the setting of stereotactic body radiation
therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). A search was
conducted in the PubMed electronic databases in August 2011. In the studies
analyzed, increasing the alpha/beta ratio is associated with an increase in the
strength of the correlation between isocenter BED and local control, especially
in the studies with median followup of >=24 months, for which Spearman's
correlation coefficients of 0.74-0.76 were achieved for alpha/beta of 20 Gy, 30
Gy, and 50 Gy (P = 0.007-0.008). A trend toward statistical significance was
observed for the correlation of isocenter BED and the 2-year overall survival
when an alpha/beta of 20 Gy was used approached statistical significance (P =
0.073). Our results suggest that an alpha/beta > 10 Gy may be more appropriate
for the prediction of dose response in the setting of lung SBRT.
PMID- 24350268
TI - The continuing debate on deep molluscan phylogeny: evidence for Serialia
(Mollusca, Monoplacophora + Polyplacophora).
AB - Molluscs are a diverse animal phylum with a formidable fossil record. Although
there is little doubt about the monophyly of the eight extant classes,
relationships between these groups are controversial. We analysed a comprehensive
multilocus molecular data set for molluscs, the first to include multiple species
from all classes, including five monoplacophorans in both extant families. Our
analyses of five markers resolve two major clades: the first includes gastropods
and bivalves sister to Serialia (monoplacophorans and chitons), and the second
comprises scaphopods sister to aplacophorans and cephalopods. Traditional
groupings such as Testaria, Aculifera, and Conchifera are rejected by our data
with significant Approximately Unbiased (AU) test values. A new molecular clock
indicates that molluscs had a terminal Precambrian origin with rapid divergence
of all eight extant classes in the Cambrian. The recovery of Serialia as a
derived, Late Cambrian clade is potentially in line with the stratigraphic
chronology of morphologically heterogeneous early mollusc fossils. Serialia is in
conflict with traditional molluscan classifications and recent phylogenomic data.
Yet our hypothesis, as others from molecular data, implies frequent molluscan
shell and body transformations by heterochronic shifts in development and
multiple convergent adaptations, leading to the variable shells and body plans in
extant lineages.
PMID- 24350267
TI - Acoustic droplet vaporization in biology and medicine.
AB - This paper reviews the literature regarding the use of acoustic droplet
vaporization (ADV) in clinical applications of imaging, embolic therapy, and
therapeutic delivery. ADV is a physical process in which the pressure waves of
ultrasound induce a phase transition that causes superheated liquid nanodroplets
to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other
functions. ADV of perfluoropentane was used extensively in imaging for
preclinical trials in the 1990s, but its use declined rapidly with the advent of
other imaging agents. In the last decade, ADV was proposed and explored for
embolic occlusion therapy, drug delivery, aberration correction, and high
intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has
been explored in rodents and dogs and may be approaching clinical use. ADV for
drug delivery is still in preclinical stages with initial applications to treat
tumors in mice. Other techniques are still in preclinical studies but have
potential for clinical use in specialty applications. Overall, ADV has a bright
future in clinical application because the small size of nanodroplets greatly
reduces the rate of clearance compared to larger contrast agent bubbles and yet
provides the advantages of ultrasonographic contrast, acoustic cavitation, and
nontoxicity of conventional perfluorocarbon contrast agent bubbles.
PMID- 24350269
TI - Enhancement of oxygen mass transfer and gas holdup using palm oil in stirred tank
bioreactors with xanthan solutions as simulated viscous fermentation broths.
AB - Volumetric mass transfer coefficient (kLa) is an important parameter in
bioreactors handling viscous fermentations such as xanthan gum production, as it
affects the reactor performance and productivity. Published literatures showed
that adding an organic phase such as hydrocarbons or vegetable oil could increase
the kLa. The present study opted for palm oil as the organic phase as it is
plentiful in Malaysia. Experiments were carried out to study the effect of
viscosity, gas holdup, and kLa on the xanthan solution with different palm oil
fractions by varying the agitation rate and aeration rate in a 5 L bench-top
bioreactor fitted with twin Rushton turbines. Results showed that 10% (v/v) of
palm oil raised the kLa of xanthan solution by 1.5 to 3 folds with the highest
kLa value of 84.44 h(-1). It was also found that palm oil increased the gas
holdup and viscosity of the xanthan solution. The kLa values obtained as a
function of power input, superficial gas velocity, and palm oil fraction were
validated by two different empirical equations. Similarly, the gas holdup
obtained as a function of power input and superficial gas velocity was validated
by another empirical equation. All correlations were found to fit well with
higher determination coefficients.
PMID- 24350270
TI - Acid lipase from Candida viswanathii: production, biochemical properties, and
potential application.
AB - Influences of environmental variables and emulsifiers on lipase production of a
Candida viswanathii strain were investigated. The highest lipase activity (101.1
U) was observed at 210 rpm, pH 6.0, and 27.5 degrees C. Other fermentation
parameters analyzed showed considerable rates of biomass yield (Y L/S = 1.381
g/g), lipase yield (Y L/S = 6.892 U/g), and biomass productivity (P X = 0.282
g/h). Addition of soybean lecithin increased lipase production in 1.45-fold,
presenting lipase yield (Y L/S ) of 10.061 U/g. Crude lipase presented optimal
activity at acid pH of 3.5, suggesting a new lipolytic enzyme for this genus and
yeast in general. In addition, crude lipase presented high stability in acid
conditions and temperature between 40 and 45 degrees C, after 24 h of incubation
in these temperatures. Lipase remained active in the presence of organic solvents
maintaining above 80% activity in DMSO, methanol, acetonitrile, ethanol, acetone,
1-propanol, isopropanol, and 2-propanol. Effectiveness for the hydrolysis of a
wide range of natural triglycerides suggests that this new acid lipase has high
potential application in the oleochemical and food industries for hydrolysis
and/or modification of triacylglycerols to improve the nutritional properties.
PMID- 24350271
TI - The importance and perspective of magnetic resonance imaging in the evaluation of
endometriosis.
AB - MR imaging is becoming increasingly important in the assessment of patients with
endometriosis. Its multiplanar capabilities and superior soft tissue contrast are
particularly useful in the detection of deep infiltrating endometriotic implants.
Endometriosis, defined as the presence of endometrial glands and stroma outside
the endometrium, is among the most common gynaecological disorders affecting
women in their reproductive age. The diagnosis and evaluation of the extension of
endometriosis are difficult only with physical examination and laparoscopy.
According to the authors' personal experience, a special MRI technique and some
imaging guidelines regarding different anatomical localizations of endometriosis
are discussed. This review is a brief presentation of current evidence on the
diagnostic accuracy of MRI in the evaluation of endometriosis concerning other
diagnostic methods, the limitations of MRI and its essential usefulness for
preoperative diagnosis of deep pelvic endometriosis, and future perspectives in
monitoring this disease.
PMID- 24350272
TI - An improved biometrics-based remote user authentication scheme with user
anonymity.
AB - The authors review the biometrics-based user authentication scheme proposed by An
in 2012. The authors show that there exist loopholes in the scheme which are
detrimental for its security. Therefore the authors propose an improved scheme
eradicating the flaws of An's scheme. Then a detailed security analysis of the
proposed scheme is presented followed by its efficiency comparison. The proposed
scheme not only withstands security problems found in An's scheme but also
provides some extra features with mere addition of only two hash operations. The
proposed scheme allows user to freely change his password and also provides user
anonymity with untraceability.
PMID- 24350273
TI - Ligand-specific regulation of the endogenous mu-opioid receptor by chronic
treatment with mu-opioid peptide agonists.
AB - Since the discovery of the endomorphins (EM), the postulated endogenous peptide
agonists of the mu-opioid receptors, several analogues have been synthesized to
improve their binding and pharmacological profiles. We have shown previously that
a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid(2)-endomorphin-2 (ACHC
EM2), had elevated mu-receptor affinity, selectivity, and proteolytic stability
over the parent compound. In the present work, we have studied its
antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a
somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2
(45%), which peaked at 10 min after intracerebroventricular (icv) administration
in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive
effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day
treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins
in subcellular fractions of rat brain. Also, the density of mu-receptors was
upregulated by about 40% in the light membrane fraction, with no detectable
changes in surface binding. Distinct receptor regulatory processes were noted in
subcellular fractions of rat brains made tolerant by the prototypic full mu
agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These
results are discussed in light of the recently discovered phenomenon, that is,
the "so-called biased agonism" or "functional selectivity".
PMID- 24350274
TI - Cytotoxicity and genotoxicity evaluation of organochalcogens in human leucocytes:
a comparative study between ebselen, diphenyl diselenide, and diphenyl
ditelluride.
AB - Organochalcogens, particularly ebselen, have been used in experimental and
clinical trials with borderline efficacy. (PhSe)2 and (PhTe)2 are the simplest of
the diaryl dichalcogenides and share with ebselen pharmacological properties. In
view of the concerns with the use of mammals in studies and the great number of
new organochalcogens with potential pharmacological properties that have been
synthesized, it becomes important to develop screening protocols to select
compounds that are worth to be tested in vivo. This study investigated the
possible use of isolated human white cells as a preliminary model to test
organochalcogen toxicity. Human leucocytes were exposed to 5-50 MUM of ebselen,
(PhSe)2, or (PhTe)2. All compounds were cytotoxic (Trypan's Blue exclusion) at
the highest concentration tested, and Ebselen was the most toxic. Ebselen and
(PhSe)2 were genotoxic (Comet Assay) only at 50 MUM, and (PhTe)2 at 5-50 MUM.
Here, the acute cytotoxicity did not correspond with in vivo toxicity of the
compounds. But the genotoxicity was in the same order of the in vivo toxicity to
mice. These results indicate that in vitro genotoxicity in white blood cells
should be considered as an early step in the investigation of potential toxicity
of organochalcogens.
PMID- 24350275
TI - Ropivacaine-induced contraction is attenuated by both endothelial nitric oxide
and voltage-dependent potassium channels in isolated rat aortae.
AB - This study investigated endothelium-derived vasodilators and potassium channels
involved in the modulation of ropivacaine-induced contraction. In endothelium
intact rat aortae, ropivacaine concentration-response curves were generated in
the presence or absence of the following inhibitors: the nonspecific nitric oxide
synthase (NOS) inhibitor N (omega) -nitro-L-arginine methyl ester (L-NAME), the
neuronal NOS inhibitor N (omega) -propyl-L-arginine hydrochloride, the inducible
NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase
(GC) inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide
3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor
fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4
AP), the calcium-activated potassium channel inhibitor tetraethylammonium (TEA),
the inward-rectifying potassium channel inhibitor barium chloride, and the ATP
sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on
endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein
endothelial cells was examined by western blotting. Ropivacaine-induced
contraction was weaker in endothelium-intact aortae than in endothelium-denuded
aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction,
whereas wortmannin, N (omega) -propyl-L-arginine hydrochloride, 1400W
dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine
induced contraction; however, barium chloride and glibenclamide had no effect.
eNOS phosphorylation was induced by ropivacaine. These results suggest that
ropivacaine-induced contraction is attenuated primarily by both endothelial
nitric oxide and voltage-dependent potassium channels.
PMID- 24350276
TI - Effects of seawater salinity and temperature on growth and pigment contents in
Hypnea cervicornis J. Agardh (Gigartinales, Rhodophyta).
AB - This study simulated outdoor environmental living conditions and observed the
growth rates and changes of several photosynthetic pigments (Chl a, Car, PE, and
PC) in Hypnea cervicornis J. Agardh (Gigartinales, Rhodophyta) by setting up
different ranges of salinity (25, 30, 35, 40, 45, and 50) and temperature (15,
20, 25, and 30 degrees C). At conditions of culture, the results are as follows.
(1) Changes in salinity and temperature have significant effects on the growth of
H. cervicornis. The growth rates first increase then decrease as the temperature
increases, while growth tends to decline as salinity increases. The optimum
salinity and temperature conditions for growth are 25 and 25 degrees C,
respectively. (2) Salinity and temperature have significant or extremely
significant effects on photosynthetic pigments (Chl a, Car, PE, and PC) in H.
cervicornis. The results of this study are advantageous to ensure propagation and
economic development of this species in the southern sea area of China.
PMID- 24350277
TI - Purification and characterization of tannin acyl hydrolase produced by mixed
solid state fermentation of wheat bran and marigold flower by Penicillium notatum
NCIM 923.
AB - Tannin acyl hydrolase produced extracellularly by the fungal strain Penicillium
notatum NCIM 923 in mixed solid state fermentation of wheat bran and marigold
flower in the ratio 4 : 1 was purified from the cell-free extract broth by
ammonium sulphate fractionation followed by diethylaminoethyl-cellulose column
chromatography. Tannase was purified by 19.89-fold with yield of 11.77%. The
specific activity of crude tannase was found to be 1.31 U/mg protein while that
of purified tannase was 22.48 U/mg protein. SDS-PAGE analysis indicated that the
enzyme is dimeric with one major band of molecular mass 97 kDa and a very light
band of molecular mass 43 kDa. Temperature of 35 to 40 degrees C and pH 5 were
optimum for tannase activity. The enzyme retained more than 60% of its stability
at 60 degrees C and 40% stability at pH 3 and 8, respectively. K m was found to
be 0.33 * 10(-2) M and V max = 40 U/mg. Since the enzyme is active over a wide
range of pH and temperature, it could find potential use in the food processing
industry.
PMID- 24350278
TI - Immunohistochemical analysis of P63 expression in odontogenic lesions.
AB - P63 may have a role in tumorigenesis and cytodifferentiation of odontogenic
lesions. We investigated the immunohistochemical expression of P63 in a total of
30 cases of odontogenic cysts and tumors. The percentage of positive cells was
calculated in the lining of odontogenic cysts and islands of ameloblastoma. P63
expression was evident in all types of odontogenic lesions. P63 was expressed
throughout the lining epithelium of odontogenic keratocyst except surface
parakeratinized layer. In addition, calcifying odontogenic cyst showed P63
expression in all layers. In almost all radicular and dentigerous cysts, the
basal and parabasal layers were immunoreactive. Peripheral cells of ameloblastoma
expressed P63; however, stellate reticulum had weaker immunostaining. No
significant difference in P63 expression was observed between studied lesions (P
= 0.86). Expression of P63 in odontogenic lesions suggests that this protein is
important in differentiation and proliferation of odontogenic epithelial cells.
However, it seems that it could not be a useful marker to differentiate between
aggressive and nonaggressive lesions. P63 also represents a progenitor or basal
cell marker, and it is not expressed in mature differentiated cells.
PMID- 24350279
TI - Association of CILP2 and ACE gene polymorphisms with cardiovascular risk factors
in Slovak midlife women.
AB - The aim of this study is to assess the association of two polymorphisms, the
cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting
enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical
parameters related to the development of cardiovascular disease. The entire study
sample comprised 341 women ranging in age from 39 to 65 years. The CILP2
genotypes were determined by PCR-RFLP and the ACE genotypes by PCR. The
Bonferroni pairwise comparisons showed the effect of the CILP2 genotype on high
density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL
C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to
HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (P < 0.05). Here, higher
mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid
parameters were registered in the GT/TT genotype carriers than in GG carriers.
Statistically significant association was identified between the ACE genotype and
the following parameters: TC, LDL-C, and non-HDL-C (P < 0.05). The II genotype
can lower serum level of TC (B = 0.40), LDL-C (B = 0.37), and non-HDL-C levels.
The results of this study suggest that the minor T allele of CILP2 gene and I
allele of ACE gene have a protective effect against elevated serum lipid and
lipoprotein levels.
PMID- 24350280
TI - Expression sensitivity analysis of human disease related genes.
AB - Background. Genome-wide association studies (GWAS) have shown its revolutionary
power in seeking the influenced loci on complex diseases genetically. Thousands
of replicated loci for common traits are helpful in diseases risk assessment.
However it is still difficult to elucidate the variations in these loci that
directly cause susceptibility to diseases by disrupting the expression or
function of a protein currently. Results. We evaluate the expression features of
disease related genes and find that different diseases related genes show
different expression perturbation sensitivities in various conditions. It is
worth noting that the expression of some robust disease-genes doesn't show
significant change in their corresponding diseases, these genes might be easily
ignored in the expression profile analysis. Conclusion. Gene ontology enrichment
analysis indicates that robust disease-genes execute essential function in
comparison with sensitive disease-genes. The diseases associated with robust
genes seem to be relatively lethal like cancer and aging. On the other hand, the
diseases associated with sensitive genes are apparently nonlethal like psych and
chemical dependency diseases.
PMID- 24350281
TI - Ultraviolet-visible and fluorescence spectroscopy techniques are important
diagnostic tools during the progression of atherosclerosis: diet zinc
supplementation retarded or delayed atherosclerosis.
AB - BACKGROUND: In this study, we examined whether UV-visible and fluorescence
spectroscopy techniques detect the progression of atherosclerosis in serum of
rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD +
Zn) compared with the control. METHODS: The control rabbits group was fed on 100
g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow
supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same
period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus
1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same
feeding period. UV-visible and fluorescence spectroscopy and biochemistry in
Rabbit's blood serum and blood hematology were measured in Rabbit's blood.
RESULTS: We found that the fluorescent peak of HCD shifted toward UV-visible
wavelength compared with the control using fluorescent excitation of serum at 192
nm. In addition, they showed that supplementation of zinc (350 ppm) restored the
fluorescent peak closely to the control. By using UV-visible spectroscopy
approach, we found that the peak absorbance of HCD (about 280 nm) was higher than
that of control and that zinc supplementation seemed to decrease the absorbance.
CONCLUSIONS: This study demonstrates that ultraviolet-visible and fluorescence
spectroscopy techniques can be applied as noninvasive techniques on a sample
blood serum for diagnosing or detecting the progression of atherosclerosis. The
Zn supplementation to rabbits fed on HCD delays or retards the progression of
atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of
atherosclerosis.
PMID- 24350282
TI - P-glycoprotein-activity measurements in multidrug resistant cell lines: single
cell versus single-well population fluorescence methods.
AB - BACKGROUND: P-gp expression has been linked to the efflux of chemotherapeutic
drugs in human cancers leading to multidrug resistance. Fluorescence techniques
have been widely applied to measure the P-gp activity. In this paper, there is a
comparison between the advantages of two fluorescence approaches of commonly
available and affordable instruments: the microplate reader (MPR) and the flow
cytometer to detect the P-gp efflux activity using calcein-AM. RESULTS: The
selectivity, sensibility, and reproducibility of the two methods have been
defined. Our results showed that the MPR is more powerful for the detection of
small inhibition, whereas the flow cytometry method is more reliable at higher
concentrations of the inhibitors. We showed that to determine precisely the
inhibition efficacy the flow cytometry is better; hence, to get the correct E max
and EC50 values, we cannot only rely on the MPR. CONCLUSION: Both techniques can
potentially be used extensively in the pharmaceutical industry for high
throughput drug screening and in biology laboratories for academic research,
monitoring the P-gp efflux in specific assays.
PMID- 24350283
TI - Role of intracellular Ca2+ and Na+/Ca2+ exchanger in the pathogenesis of contrast
induced acute kidney injury.
AB - The precise mechanisms underlying contrast-induced acute kidney injury (CI-AKI)
are not well understood. Intracellular Ca(2+) overload is considered to be a key
factor in CI-AKI. Voltage-dependent Ca(2+) channel (VDC) and Na(+)/Ca(2+)
exchanger (NCX) system are the main pathways of intracellular Ca(2+) overload in
pathological conditions. Here, we review the potential underlying mechanisms
involved in CI-AKI and discuss the role of NCX-mediated intracellular Ca(2+)
overload in the contrast media-induced renal tubular cell injury and renal
hemodynamic disorder.
PMID- 24350284
TI - Changes of regulatory T and B cells in patients with papillary thyroid carcinoma
after 131I radioablation: a preliminary study.
AB - Introduction. Lymphocytic infiltration and specific lymphocytes subsets may play
important roles in papillary thyroid carcinoma (PTC) progression and prognosis.
In this study, we try to understand the influence of (131)I radioablation on the
important lymphocytes subtypes of regulatory T and B cells (Tregs and Bregs).
Methods. Peripheral blood mononuclear cells from 30 PTC patients before and after
(131)I therapy, and 20 healthy donors were collected. The expression of Tregs
(CD4(+)CD25(+)CD127(-/low)) and B cell (CD5(+)CD19(+)) and production and
secretion of interleukin 10 (IL-10) were analyzed by FACS and ELISA assay,
respectively. Results. For Tregs percentage in peripheral blood lymphocytes,
there was no difference between pretreatment and control and between
posttreatment and control. Compared with pretherapy, increased Tregs infiltration
was noted in posttherapy (P < 0.05). Although no difference was between
pretreatment and control, compared with these two groups, decreased CD19(+) and
CD5(+)CD19(+) B cell percentage in posttreatment was observed (P < 0.05). Among
these groups, no significant difference was displayed in intracellular IL-10
production and extracellular IL-10 secretion. Conclusions. (131)I Radioablation
increased Tregs and decreased CD19(+) and CD5(+)CD19(+) B cells percentage after
treatment. However, it has no effect on IL-10 and lymphocytes in peripheral
blood. Therefore, longer follow-up of Tregs and Bregs should be further
investigated.
PMID- 24350285
TI - Usefulness of traditional serum biomarkers for management of breast cancer
patients.
AB - The measurement of serum tumor markers levels in breast cancer (BC) patients is
an economic and noninvasive diagnostic assay frequently requested by clinical
oncologists to get information about the presence or absence of disease as well
as its evolution. Despite their wide use in clinical practice, there is still an
intense debate between scientific organizations about the real usefulness for
patient monitoring during followup as well as response to therapy evaluation in
case of advanced BC. In this review, we want to highlight the current
recommendations published by scientific organizations about the use of
"established" BC serum markers (CEA, TPA, TPS, CIFRA-21, CA15-3, and s-HER2) in
clinical oncology practice. Moreover, we will focus on recent papers evidencing
the usefulness of tumor markers levels measurement as a guide for the
prescription and diagnostic integration of molecular imaging exams such as those
performed by hybrid 18-fluorofeoxyglucose-positron emission tomography with
integrated computed tomography. This technology is nowadays able to detect early
cancer lesions undetectable by conventional morphological imaging investigation
and most likely responsible for increasing of serum tumor markers levels.
PMID- 24350286
TI - A systems' biology approach to study microRNA-mediated gene regulatory networks.
AB - MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where
aberrant miRNA expression can contribute to human diseases such as cancer. For a
better understanding of the regulatory role of miRNAs in coordinating gene
expression, we here present a systems biology approach combining data-driven
modeling and model-driven experiments. Such an approach is characterized by an
iterative process, including biological data acquisition and integration, network
construction, mathematical modeling and experimental validation. To demonstrate
the application of this approach, we adopt it to investigate mechanisms of
collective repression on p21 by multiple miRNAs. We first construct a p21
regulatory network based on data from the literature and further expand it using
algorithms that predict molecular interactions. Based on the network structure, a
detailed mechanistic model is established and its parameter values are determined
using data. Finally, the calibrated model is used to study the effect of
different miRNA expression profiles and cooperative target regulation on p21
expression levels in different biological contexts.
PMID- 24350287
TI - Prooxidant mechanisms in iron overload cardiomyopathy.
AB - Iron overload cardiomyopathy (IOC), defined as the presence of systolic or
diastolic cardiac dysfunction secondary to increased deposition of iron, is
emerging as an important cause of heart failure due to the increased incidence of
this disorder seen in thalassemic patients and in patients of primary
hemochromatosis. At present, although palliative treatment by regular iron
chelation was recommended; whereas IOC is still the major cause for mortality in
patient with chronic heart failure induced by iron-overloading. Because iron is a
prooxidant and the associated mechanism seen in iron-overload heart is still
unclear; therefore, we intend to delineate the multiple signaling pathways
involved in IOC. These pathways may include organelles such as calcium channels,
mitochondria; paracrine effects from both macrophages and fibroblast, and novel
mediators such as thromboxane A2 and adiponectin; with increased oxidative stress
and inflammation found commonly in these signaling pathways. With further
understanding on these complex and inter-related molecular mechanisms, we can
propose potential therapeutic strategies to ameliorate the cardiac toxicity
induced by iron-overloading.
PMID- 24350288
TI - MHC universal cells survive in an allogeneic environment after incompatible
transplantation.
AB - Cell, tissue, and organ transplants are commonly performed for the treatment of
different diseases. However, major histocompatibility complex (MHC) diversity
often prevents complete donor-recipient matching, resulting in graft rejection.
This study evaluates in a preclinical model the capacity of MHC class I-silenced
cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA
targeting beta2-microglobulin (RN_shbeta2m) was delivered into fibroblasts
derived from LEW/Ztm (RT1(l)) (RT1-A(l)) rats using a lentiviral-based vector.
MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously
in LEW rats (RT1(l)) and MHC-congenic LEW.1W rats (RT1(u)), respectively. Cell
engraftment and the status of the immune response were monitored for eight weeks
after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced
fibroblasts became engrafted and were still detectable eight weeks after
allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1 alpha
, IL-1 beta , IL-6, TNF- alpha , and IFN- gamma were significantly higher in
animals transplanted with RT1-A-expressing cells than in those receiving RT1-A
silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates
derived from rats receiving RT1-A-expressing cells were higher than those in rats
transplanted with RT1-A-silenced cells. These data suggest that silencing MHC
class I expression might overcome the histocompatibility barrier, potentially
opening up new avenues in the field of cell transplantation and regenerative
medicine.
PMID- 24350289
TI - Identifying breast cancer subtype related miRNAs from two constructed miRNAs
interaction networks in silico method.
AB - BACKGROUND: It has been known that microRNAs (miRNAs) regulate the expression of
multiple proteins and therefore are likely to emerge as more effective targets of
selective therapeutic modalities for breast cancer. Although recent lines of
evidence have approved that miRNAs are associated with the most common molecular
breast cancer subtypes, the studies to breast cancer subtypes have not been well
characterized. OBJECTIVES: In this study, we propose a silico method to identify
breast cancer subtype related miRNAs based on two constructed miRNAs interaction
networks using miRNA-mRNA dual expression profiling data arising from the same
samples. METHODS: Firstly, we used a new mutual information estimation method to
construct two miRNAs interaction networks based on miRNA-mRNA dual expression
profiling data. Secondly, we compared and analyzed the topological properties of
these two networks. Finally, miRNAs showing the outstanding topological
properties in both of the two networks were identified. Results. Further
functional analysis and literature evidence confirm that the identified potential
breast cancer subtype related miRNAs are essential to unraveling their biological
function. CONCLUSIONS: This study provides a new silico method to predict
candidate miRNAs of breast cancer subtype from a system biology level and can
help exploit for functional studies of important breast cancer subtype related
miRNAs.
PMID- 24350290
TI - Parthenium hysterophorus: a probable source of anticancer, antioxidant and anti
HIV agents.
AB - The present work reports the anticancer, antioxidant, lipo-protective, and anti
HIV activities of phytoconstituents present in P. hysterophorus leaf. Dried leaf
samples were sequentially extracted with nonpolar and polar solvents. Ethanol
fraction showed noticeable cytotoxic activity (81-85%) in SRB assay against MCF-7
and THP-1 cancer cell lines at 100 MUg/ml concentration, while lower activity
was observed with DU-145 cell line. The same extract exhibited 17-98% growth
inhibition of HL-60 cancer cell lines in MTT assay, showing concentration
dependent response. Ethanol extract caused 12% reduction in mitochondrial
membrane potential and 10% increment in sub G1 population of HL-60 cell lines.
Several leaf fractions, namely, ethyl acetate, ethanol, and aqueous fractions
exhibited considerable reducing capability at higher concentrations. Most of the
extracts demonstrated appreciable (>75%) metal ion chelating and hydroxyl radical
scavenging activities at 200 ug/ml. All the extracts except aqueous fraction
accounted for about 70-80% inhibition of lipid peroxidation in rat liver
homogenate indicating protective response against membrane damage. About 40%
inhibition of reverse transcriptase (RT) activity was observed in hexane fraction
in anti-HIV assay at 6.0 ug/ml concentration. The study showed that
phytochemicals present in P. hysterophorus leaf have considerable potential as
cytotoxic and antioxidant agents with low to moderate anti-HIV activity.
PMID- 24350292
TI - Integration of data from omic studies with the literature-based discovery towards
identification of novel treatments for neovascularization in diabetic
retinopathy.
AB - Diabetic retinopathy (DR) is a secondary complication of diabetes associated with
retinal neovascularization and represents the leading cause of blindness in the
adult population in the developed world. Despite research efforts, the nature of
pathogenetic processes leading to DR is still unknown, making development of
novel effective treatments difficult. Advances in omic technologies now offer
unprecedented insight into global molecular alterations in DR, but identification
of novel treatments based on massive amounts of data generated in omic studies
still represents a considerable challenge. For this reason, we attempted to
facilitate discovery of novel treatments for DR by complementing the
interpretation of omic results using the vast body of information existing in the
published literature with the literature-based discovery (LBD) approaches. To
achieve this, we collected data from transcriptomic studies performed on retinal
tissue from animal models of DR, performed a meta-analysis of these datasets and
identified altered genes and pathways. Using the SemBT LBD framework, we have
determined which therapies could regulate perturbed pathways or that could
stabilize the gene expression alterations in DR. We show that by using this
approach, we not only could reidentify drugs currently in use or in clinical
trials, but also could indicate novel treatment directions for ameliorating
neovascularization processes in DR.
PMID- 24350291
TI - Tumor necrosis factor receptor 2: its contribution to acute cellular rejection
and clear cell renal carcinoma.
AB - Tumor necrosis factor receptor 2 (TNFR2) is a type I transmembrane glycoprotein
and one of the two receptors that orchestrate the complex biological functions of
tumor necrosis factor (TNF, also designed TNF- alpha ). Accumulating experimental
evidence suggests that TNFR2 plays an important role in renal disorders
associated with acute cellular rejection and clear cell renal carcinoma but its
exact role in these settings is still not completely understood. This papers
reviews the factors that may mediate TNFR2 induction in acute cellular rejection
and clear cell renal carcinoma and its contribution to these conditions and
discusses its therapeutic implications. A greater understanding of the function
of TNFR2 may lead to the development of new anti-TNF drugs.
PMID- 24350293
TI - Treatment of Chagas cardiomyopathy.
AB - Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was
discovered and described by the Brazilian physician Carlos Chagas in 1909. After
a century of original description, trypanosomiasis still brings much misery to
humanity and is classified as a neglected tropical disease prevalent in
underdeveloped countries, particularly in South America. It is an increasing
worldwide problem due to the number of cases in endemic areas and the migration
of infected subjects to more developed regions, mainly North America and Europe.
Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is
yet poorly understood, and independently of its social, clinical, and
epidemiological importance, the therapeutic approach of CCC is still transposed
from the knowledge acquired from other cardiomyopathies. Therefore, the objective
of this review is to describe the treatment of Chagas cardiomyopathy with
emphasis on its peculiarities.
PMID- 24350295
TI - Depletion of luminal pyridine nucleotides in the endoplasmic reticulum activates
autophagy with the involvement of mTOR pathway.
AB - It has been recently shown that redox imbalance of luminal pyridine nucleotides
in the endoplasmic reticulum (ER) together with oxidative stress results in the
activation of autophagy. In the present study we demonstrated that decrease of
luminal NADPH/NADP(+) ratio alone by metyrapone was sufficient to promote the
mechanism of "self-eating" detected by the activation of LC3. Depletion of
luminal NADPH had also significant effect on the key proteins of mTOR pathway,
which got inactivated by dephosphorylation. These findings were also confirmed by
silencing the proteins (glucose-6-phosphate transporter and hexose-6-phosphate
dehydrogenase) responsible for NADPH generation in the ER lumen. However,
silencing the key components and addition of metyrapone had different effects on
downstream substrates 4EBP1 and p70S6K of mTOR. The applied treatments did not
compromise the viability of the cells. Our data suggest that ER stress caused by
luminal NADPH depletion activates a pro-survival autophagic mechanism firmly
coupled to the activation of mTOR pathway.
PMID- 24350294
TI - From single nucleotide polymorphisms to constant immunosuppression: mesenchymal
stem cell therapy for autoimmune diseases.
AB - The regenerative abilities and the immunosuppressive properties of mesenchymal
stromal cells (MSCs) make them potentially the ideal cellular product of choice
for treatment of autoimmune and other immune mediated disorders. Although the
usefulness of MSCs for therapeutic applications is in early phases, their
potential clinical use remains of great interest. Current clinical evidence of
use of MSCs from both autologous and allogeneic sources to treat autoimmune
disorders confers conflicting clinical benefit outcomes. These varied results may
possibly be due to MSC use across wide range of autoimmune disorders with
clinical heterogeneity or due to variability of the cellular product. In the
light of recent genome wide association studies (GWAS), linking predisposition of
autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible
genetic loci, the clinical relevance of MSCs possessing SNPs in the critical
effector molecules of immunosuppression is largely undiscussed. It is of further
interest in the allogeneic setting, where SNPs in the target pathway of MSC's
intervention may also modulate clinical outcome. In the present review, we have
discussed the known critical SNPs predisposing to disease susceptibility in
various autoimmune diseases and their significance in the immunomodulatory
properties of MSCs.
PMID- 24350296
TI - Use of Frankia and actinorhizal plants for degraded lands reclamation.
AB - Degraded lands are defined by soils that have lost primary productivity due to
abiotic or biotic stresses. Among the abiotic stresses, drought, salinity, and
heavy metals are the main threats in tropical areas. These stresses affect plant
growth and reduce their productivity. Nitrogen-fixing plants such as actinorhizal
species that are able to grow in poor and disturbed soils are widely planted for
the reclamation of such degraded lands. It has been reported that association of
soil microbes especially the nitrogen-fixing bacteria Frankia with these
actinorhizal plants can mitigate the adverse effects of abiotic and biotic
stresses. Inoculation of actinorhizal plants with Frankia significantly improves
plant growth, biomass, shoot and root N content, and survival rate after
transplanting in fields. However, the success of establishment of actinorhizal
plantation in degraded sites depends upon the choice of effective strains of
Frankia. Studies related to the beneficial role of Frankia on the establishment
of actinorhizal plants in degraded soils are scarce. In this review, we describe
some examples of the use of Frankia inoculation to improve actinorhizal plant
performances in harsh conditions for reclamation of degraded lands.
PMID- 24350297
TI - Plasma levels of soluble HLA-E and HLA-F at diagnosis may predict overall
survival of neuroblastoma patients.
AB - The purpose of this study was to identify the plasma/serum biomarkers that are
able to predict overall survival (OS) of neuroblastoma (NB) patients.
Concentration of soluble (s) biomarkers was evaluated in plasma (sHLA-E, sHLA-F,
chromogranin, and B7H3) or serum (calprotectin) samples from NB patients or
healthy children. The levels of biomarkers that were significantly higher in NB
patients were then analyzed considering localized or metastatic subsets. Finally,
biomarkers that were significantly different in these two subsets were correlated
with patient's outcome. With the exception of B7H3, levels of all molecules were
significantly higher in NB patients than those in controls. However, only
chromogranin, sHLA-E, and sHLA-F levels were different between patients with
metastatic and localized tumors. sHLA-E and -F levels correlated with each other
but not chromogranin. Chromogranin levels correlated with different event-free
survival (EFS), whereas sHLA-E and -F levels also correlated with different OS.
Association with OS was also detected considering only patients with metastatic
disease. In conclusion, low levels of sHLA-E and -F significantly associated with
worse EFS/OS in the whole cohort of NB patients and in patients with metastatic
NB. Thus, these molecules deserve to be tested in prospective studies to evaluate
their predictive power for high-risk NB patients.
PMID- 24350298
TI - Levels of inflammatory cytokines in type 2 diabetes patients with different
urinary albumin excretion rates and their correlation with clinical variables.
AB - Although the pathogenetic mechanism of DN has not been elucidated, an
inflammatory mechanism has been suggested as a potential contributor. This study
was designed to explore the relationship between low-grade inflammation and renal
microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three
groups according to UAE: a normal albuminuria group, a microalbuminuria group,
and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP,
TNF-alpha, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were
measured in all subjects. Compared with the normal controls, levels of hs-CRP,
TNF-alpha, uMCP-1, and SAA in T2DM patients were significantly higher. They were
also elevated in the normal albuminuria group, P < 0.05. Compared with the normal
albuminuria group, levels of these inflammatory cytokines were significantly
higher in the microalbuminuria and macroalbuminuria group, P < 0.01. The
macroalbuminuria group also showed higher levels than the microalbuminuria group,
P < 0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC.
We noted no significance correlated with course, TG, or HDL-C. Only TNF-alpha;
was positively correlated with HbA1c. This study revealed the importance of these
inflammatory cytokines in DN pathogenesis. Further studies are needed to fully
establish the potential of these cytokines as additional biomarkers for the
development of DN.
PMID- 24350299
TI - Evaluation of the association of plasma pentraxin 3 levels with type 2 diabetes
and diabetic nephropathy in a Malay population.
AB - Recent reports have demonstrated that elevated plasma long pentraxin 3 (PTX3)
levels are associated with cardiovascular and chronic kidney diseases. In the
current study, we investigated the plasma PTX3 levels in 296 Malay subjects
including the subjects with normal glucose tolerance (NGT) and type 2 diabetes
(T2DM) patients with or without DN by using an enzyme-linked immune-sorbent
assay. Results showed that in males, plasma PTX3 levels in T2DM patients without
DN were lower than that in the subjects with NGT (2.78 versus 3.98 ng/mL; P =
0.021). Plasma PTX3 levels in T2DM patients with DN were decreased compared to
the patients without DN (1.63 versus 2.78 ng/mL; P = 0.013). In females, however,
no significant alteration of plasma PTX3 levels among NGT subjects and T2DM
patients with and without DN was detected. Furthermore, an inverse correlation
between PTX3 and body mass index was found in male subjects with NGT (P = 0.012;
r = -0.390), but not in male T2DM patients, neither in all females. The current
study provided the first evidence that decreased plasma PTX3 levels are
associated with T2DM and DN in Malay men and also suggested that PTX3 may have
different effects in DN and chronic kidney diseases.
PMID- 24350300
TI - Relevance of plasma obestatin and early arteriosclerosis in patients with type 2
diabetes mellitus.
AB - We investigated the correlation between obestatin and metabolic parameters and
carotid intima-media thickness (IMT) in plasma of patients with type 2 diabetes
mellitus (T2DM). We collected 103 patients aged from 60 to 83 years (69.26 +/-
5.83 years) form January, 2007 to May, 2009. All patients were divided into
normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM
according to the oral glucose tolerance test (OGTT). We found that higher levels
of fasting insulin (Fins), fasting blood glucose, 2 h OGTT glucose, homeostasis
model assessment of insulin resistance (HOMA-IR), low density lipoprotein
cholesterol, glycated haemoglobin, and C-reactive protein (CRP), as well as lower
obestatin level and higher intima-media thickness level (IMT), existed in T2DM
group compared with NGT group and IGT group (P < 0.01). Also, obestatin level was
independently associated with HOMA-IR and CRP, while IMT level was independently
associated with HOMA-IR, triglyceride, Fins, and obestatin (P < 0.01), based on
stepwise multiple regression analysis. Therefore, we deduced that the low level
of plasma obestatin might be related to early arteriosclerosis in patients with
T2DM via increasing IMT level, and elevated plasma obestatin levels might protect
T2DM patients against carotid atherosclerosis to some extent.
PMID- 24350301
TI - Correlation of abdominal fat distribution with different types of diabetes in a
Chinese population.
AB - To investigate abdominal fat distribution in Chinese subjects with diabetes and
its correlation with different types of diabetes. A total of 176 diabetic
subjects were enrolled, 92 with type 1 and 84 with type 2, with a mean age of
27.41 and 49.3 yrs. No subject has history of severe diseases. Multi-slice CT was
used to measure total abdominal adipose (TA) and visceral adipose (VA) tissues.
Subcutaneous adipose (SA) tissue was obtained by subtracting VA from TA. There
were differences between subjects with T1DM and T2DM for TA, VA, SA, VA/SA, body
mass index (BMI), triglyceride (TG) and high density lipoprotein, but not total
Cholesterol or low density lipoprotein. There were positive correlations between
TA, VA, SA, VA/SA and T1DM and T2DM (P < 0.05 and r > 0.86). In subjects with
T1DM, VA was negatively correlated with HDL, positively with BMI and age, and SA
was positively correlated with BMI and sex (P < 0.05 and r > 0.86 for all). In
subjects with T2DM, VA was positively correlated to BMI, TG and age, and SA was
positively correlated to TG and sex (P < 0.05 and r > 0.86 for all). Abdominal
fat content was positively correlated to diabetes in Chinese, which differs in
different types of diabetes.
PMID- 24350302
TI - Seroprevalence of Brucellosis and Q-Fever in Southeast Ethiopian Pastoral
Livestock.
AB - To assess seroprevalences of Brucella and C. burnetii in pastoral livestock in
southeast Ethiopia, a cross-sectional study was carried out in three livestock
species (cattle, camels and goats). The study was conducted from July 2008 to
August 2010, and eight pastoral associations (PAs) from the selected districts
were included in the study. Sera from a total of 1830 animals, comprising 862
cattle, 458 camels and 510 goats were screened initially with Rose Bengal plate
test (RBPT) for Brucella. All RBPT positive and 25% of randomly selected negative
sera were further tested by ELISA. These comprise a total of 460 animals (211
cattle, 102 camels and 147 goats). Out of sera from total of 1830 animals, 20%
were randomly selected (180 cattle, 90 camels and 98 goats) and tested for C.
burnetii using ELISA. The seroprevalences of Brucella was 1.4% (95% confidence
interval (CI), 0.8-2.6), 0.9% (95% CI, 0.3-2.7)b and 9.6% (95% CI, 5.2-17.1) in
cattle, camels and goats, respectively. Goats and older animals were at higher
risk of infection (OR=7.3, 95% CI, 2.8-19.1) and (OR=1.7 95% CI, 0.9-2.9),
respectively. Out of 98 RBPT negative camel sera, 12.0% were positive for ELISA.
The seroprevalences of C. burnetii were 31.6% (95% CI, 24.7-39.5), 90.0% (95% CI,
81.8-94.7) and 54.2% (95% CI, 46.1-62.1) in cattle, camels and goats,
respectively. We found positive animals for C. burnetii test in all tested PAs
for all animal species. Being camel and older animal was a risk factor for
infection (OR=19.0, 95% CI, 8.9-41.2) and (OR=3.6, 95% CI, 2.0-6.6),
respectively. High seropositivity of C. burnetii in all livestock species tested
and higher seropositive in goats for Brucella, implies risks of human infection
by both diseases. Thus, merit necessity of further study of both diseases in
animals and humans in the area.
PMID- 24350303
TI - A Novel Perspective on Dopaminergic Processing of Human Addiction.
AB - Converging evidence from clinical, animal, and neuroimaging experiments suggests
that the addictive behavior is associated with dysregulated dopamine
neurotransmission. The precise role of dopamine in establishment and maintenance
of addiction however is unclear. In this context animal studies on the brain
reward system and the associative memory processing provide a novel insight. It
was shown that both processing involve dopamine neurotransmission and both are
disrupted in addiction. These findings indicate that dysregulated dopamine
neurotransmission alters the brain processing of not only the reward system but
also that of the memory of association between an addictive substance and reward.
These alterations lead to maladaptive motivational behavior leading to chemical
dependency. This concept however is based mostly on the data obtained in
laboratory animals because of the paucity of human data. Due to lack of a
reliable technique to study neurotransmission in the live human brain, it has
been a problem to study the role of dopamine in human volunteers. A recently
developed dynamic molecular imaging technique however, provides an opportunity to
study these concepts in human volunteers because the technique allows detection,
mapping and measurement of dopamine released in the live human brain during task
performance.
PMID- 24350304
TI - Unachievable Region in Precision-Recall Space and Its Effect on Empirical
Evaluation.
AB - Precision-recall (PR) curves and the areas under them are widely used to
summarize machine learning results, especially for data sets exhibiting class
skew. They are often used analogously to ROC curves and the area under ROC
curves. It is known that PR curves vary as class skew changes. What was not
recognized before this paper is that there is a region of PR space that is
completely unachievable, and the size of this region depends only on the skew.
This paper precisely characterizes the size of that region and discusses its
implications for empirical evaluation methodology in machine learning.
PMID- 24350305
TI - Design, expression and characterization of a highly stable tetratricopeptide
based protein scaffold for phage display application.
AB - Tetratricopeptide repeat (TPR) is a structural motif mediating variety of protein
protein interactions. It has a high potential to serve as a small, stable and
robust, non-immunoglobulin ligand binding scaffold. In this study, we showed the
consensus approach to design the novel protein called designed tetratricopeptide
repeat (dTPR), composed of three repeated 34 amino-acid tetratricopeptide motifs.
The designed sequence was efficiently overexpressed in E. coli and purified to
homogeneity. Recombinant dTPR is monomeric in solution and preserves its
secondary structure within the pH range from 2.0 to 11.0. Its denaturation
temperature at pH 7.5 is extremely high (104.5 degrees C) as determined by
differential scanning calorimetry. At extreme pH values the protein is still very
stable: denaturation temperature is 90.1 degrees C at pH 2.0 and 60.4 degrees C
at pH 11. Chemical unfolding of the dTPR is a cooperative, two-state process both
at pH 7.5 and 2.0. The free energy of denaturation in the absence of denaturant
equals to 15.0 kcal/mol and 13.5 kcal/mol at pH 7.5 and 2.0, respectively.
Efficient expression and extraordinary biophysical properties make dTPR a
promising framework for a biotechnological application, such as generation of
specific ligand- binding molecules.
PMID- 24350306
TI - Personalization of structural PDB files.
AB - PDB format is most commonly applied by various programs to define three
dimensional structure of biomolecules. However, the programs often use different
versions of the format. Thus far, no comprehensive solution for unifying the PDB
formats has been developed. Here we present an open-source, Python-based tool
called PDBinout for processing and conversion of various versions of PDB file
format for biostructural applications. Moreover, PDBinout allows to create one's
own PDB versions. PDBinout is freely available under the LGPL licence at
http://pdbinout.ibch.poznan.pl.
PMID- 24350307
TI - Evaluation of the activity of thermostable DNA polymerases in the presence of
heme, as a key inhibitor in the real time PCR method in diagnostics of sepsis.
AB - The study aim was evaluation of the usefulness of several thermostable DNA
polymerases in real time PCR conducted in the presence of the heme. Our study had
the advantage of testing several different polymerases, one of which proved to be
the least sensitive to heme activity. We also found that there is no need of
supplementing the reaction mixture with protective substances like BSA. Selection
of the appropriate polymerase can increase the efficiency of the PCR reaction
which is very important for diagnosis of sepsis and for other analyses performed
on DNA template isolated from the blood.
PMID- 24350308
TI - Molecular genetics of PKU in Poland and potential impact of mutations on BH4
responsiveness.
AB - Tetrahydrobiopterin (BH4) has been recently approved as a treatment of patients
with phenylketonuria. However, as a confirmation of BH4-responsiveness, it might
require a very expensive trial treatment with BH4 or prolonged BH4-loading
procedures. The selection of patients eligible for BH4-therapy by means of
genotyping of the PAH gene mutations may be recommended as a complementary
approach. A population-wide genotyping study was carried out in 1286 Polish
phenyloketonuria-patients. The aim was to estimate the BH4 demand and to cover
prospectively the treatment by a National Health Fund. A total of 95 types of
mutations were identified. Genetic variants corresponding with probable BH4
responsiveness were found in 28.2% of cases. However, patients with mild or
classical phenylketonuria who require continuous treatment accounted for 11.4% of
the studied population only. Analysis of the published data shows similar
percentage of the "BH4-responsive" variants of a PAH gene in patients from other
countries of Eastern Europe. Therefore, it can be concluded, that the proportion
of phenylketonuria-patients who could benefit from the use of BH4 reaches
approximately 10% in the entire region.
PMID- 24350309
TI - Medical practice on Tristan da Cunha--the remotest island community in the world.
AB - Midway between Africa and South America, on the edge of the 'roaring 40s' (37
degrees S 12 degrees W) is an archipelago of five tiny volcanic islands. Tristan,
a British Overseas Territory, is the largest--seven miles across and rising 7,000
feet above sea level. There is no airport, no air access except for an occasional
ship's helicopter and no sheltered anchorage. The nearest port is over 1,700
miles away--a week or more by ship and the tiny harbour requires constant repair
due to the impact of the relentless South Atlantic. Ship-to-shore travel is
hazardous as passengers (and medevacs) are transferred sitting in a box hoisted
by crane to a raft or rigid inflatable boat. Tristan has traditionally had a
resident 'ships surgeon' or 'island doctor'; although these terms may not have
changed, the training and experience to fill these roles have. The island needs a
general physician with experience of primary care or a general practitioner with
experience of secondary care. Additional training is required in surgical and
gynaecological emergencies. The two authors between them had appropriate
experience in general medicine, general practice, resuscitation and critical care
and to be able to worry together is a better prospect than worrying alone--so a
joint appointment for six months seemed sensible and was found to be effective.
PMID- 24350310
TI - Improving antimicrobial prescribing: implementation of an antimicrobial i.v.-to
oral switch policy.
AB - Antimicrobial stewardship programmes reduce the risk of hospital associated
infections (HAI) and antimicrobial resistance, and include early intravenous-to
oral switch (IVOS) as a key stewardship measure. We audited the number of
patients on intravenous antimicrobials suitable for oral switch, assessed whether
prescribing guidelines were followed and reviewed prescribing documentation in
three clinical areas in the Western General Hospital, Edinburgh, in late 2012.
Following this, the first cycle results and local guidelines were presented at a
local level and at the hospital grand rounds, posters with recommendations were
distributed, joint infection consult and antimicrobial rounds commenced and an
alert antimicrobial policy was introduced before re-auditing in early 2013. We
demonstrate suboptimal prescribing of intravenous antimicrobials, with 43.9%
(43/98) of patients eligible for IVOS at the time of auditing. Only 56.1% (55/98)
followed empiric prescribing recommendations. Documentation of antimicrobial
prescribing was poor with stop dates recorded in 14.3%, indication on
prescription charts in 18.4% and in the notes in 90.8%. The commonest reason for
deferring IVOS was deteriorating clinical condition or severe sepsis. Further
work to encourage prudent antimicrobial prescribing and earlier consideration of
IVOS is required.
PMID- 24350311
TI - Assessing frailty in the acute medical admission of elderly patients.
AB - BACKGROUND: Managing acute admission of frail older patients is a challenge in
hospitals. Length of inpatient stay, inpatient mortality and the 90-day
readmission rate are significant in this group of patients. The Comprehensive
Geriatric Assessment (CGA), a multidisciplinary diagnostic and treatment process,
is the best approach for identifying medical conditions, mental health,
functional capacity and social circumstances in acute geriatric care. METHODS: A
review of the records of older patients aged 75 and over, acutely admitted to a
district general hospital in England from 15 March 2012 to 16 April 2012 was
conducted. We developed a frailty assessment tool and applied it to these
patients, in order to determine who would be classified as frail. We then
established if the patients meeting this criteria were then correctly assessed
using the CGA. All patient data were processed and analysed using a statistical
package for data analysis. RESULTS: A total of 232 patients with a mean age of
84.25 +/- 5.8 years were included. Out of these, 129 patients (55.6%) fulfilled
the frailty criteria as determined with our frailty-assessment tool; 80.6%
presented with lack of mobility over 24 hours, 69.8% were admitted with falls,
47.3% had known dementia or delirium and 45% were admitted from care homes.
Patients aged over 85 years were more likely to have frailty compared with
patients aged 75-85 years old (odds ratio [OR]: 4.78, 95% confidence interval
[CI]: 2.6-8.6, p value >0.001). Patients assessed by a front door geriatric team
were more likely to be reviewed with the CGA than those not seen by this team
(adjusted OR 2.8, 95% CI: 1-7.6, p value=0.04). CONCLUSION: The prevalence of
frailty is high in acute admissions of older patients and it is important that
they are properly identified and assessed with a CGA in order to ensure effective
multidisciplinary care.
PMID- 24350312
TI - A case of Berardinelli-Seip syndrome presenting with cirrhosis.
AB - Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive
disorder of generalised lipoatrophy, characterised by the absence of functioning
adipocytes, with lipid being stored in muscles, the liver and the pancreas. The
usual presentation is in adulthood, with manifestations of insulin resistance,
hypertriglyceridaemia and liver steatosis. Cirrhosis as the first presentation of
BSCL in a young adult is rare. We describe a patient with BSCL presenting with
cirrhosis. To the best of our knowledge this is the first case of BSCL reported
in a Sri Lankan patient.
PMID- 24350313
TI - Granulomatous cheilitis.
AB - A 19-year-old labourer presented with progressively worsening swelling of both
lips. Clinical assessment and investigations led to the diagnosis of
granulomatous cheilitis.
PMID- 24350314
TI - Intensive lifestyle intervention has little effect on cardiovascular
complications in people with type 2 diabetes.
PMID- 24350315
TI - RCPE UK consensus conference on 'Acute medicine: improving quality of care
through effective patient flow--it's everyone's business!'.
PMID- 24350316
TI - Social media: the way forward or a waste of time for physicians?
AB - Social media is everywhere; its use has grown exponentially over recent years.
The prevalence of these outlets for communication raises some interesting and
potentially risky issues for physicians. On the one hand, some believe that
physicians should have a strong social media presence and can benefit greatly
from access to a global community of peers and leaders through blogs, online
forums, Facebook, Twitter and other communication channels. Dr Anne Marie
Cunningham provides a strong case for the advantages of developing networks and
figuring out who and what to pay attention to online. On the other hand however,
others believe that the use of social media places doctors at a professional and
ethical risk and is essentially a waste of time for the already time-pressured
physician. Professor DeCamp argues that the risks of social media outweigh their
benefits. It makes it more difficult to maintain a distinction between private
and professional personas, and as we have seen, one mistyped or inappropriate
comment can have potentially negative consequences when taken out of context.
With an already time-pressured day, the priority should be patients, not tweets.
Whatever your thoughts on the benefits and risks of social media, it is here to
stay. Specific guidelines and guidance are needed to ensure that physicians who
decide to join an online community reap the benefits of global communication,
rather than regret it.
PMID- 24350317
TI - Acute kidney injury.
AB - Acute kidney injury (AKI) represents a medical emergency associated with poor
clinical outcomes. The international guideline group Kidney Disease: Improving
Global Outcomes (KDIGO) has defined AKI according to rises in serum creatinine
and/or reductions in urine output. Any patient who meets the criteria for AKI
should be reviewed to ascertain the cause of AKI and the severity of the injury
should be staged. Patients with more severe AKI are at greater risk of
progression to chronic kidney disease (CKD). The 2009 National Confidential
Enquiry into Patient Outcomes and Death (NCEPOD) reported that only 50% of
patients who died with a diagnosis with AKI received good care. The mortality
from AKI has remained unchanged for the last four decades and there are currently
no specific therapies for the majority of cases of AKI. Patients with rarer forms
of AKI need urgent renal referral for specific therapy. At present, serum
creatinine and urine output remain the best biomarkers for detecting AKI.
However, significant kidney damage has usually occurred by the time changes in
these biomarkers are manifest and newer biomarkers are under investigation.
Management of AKI is based upon general supportive measures, which includes
treatment of the underlying cause and the initiation of renal replacement therapy
(RRT) in patients with complications refractory to medical management. The
optimal choice of intravenous fluid therapy remains controversial. There is
currently renewed interest in more specific therapies for AKI secondary to
hypoperfusion and/or sepsis, which have been previously unsuccessful. A number of
therapeutic strategies are presently being explored in clinical trials.
PMID- 24350318
TI - Current practices in the management of diabetic nephropathy.
AB - The social and economic burden of treating patients with diabetes mellitus (DM)
is rapidly rising. Current projections estimate the global prevalence of
individuals with DM to rise from 6.4% (285 million) in 2010 to 7.7% (439 million)
in 2030.1 The main problem with this disease entity is its propensity to incur
macro- and micro-vascular complications over time, including diabetic nephropathy
(DN). Diabetic nephropathy affects approximately one-third of individuals with
diabetes. It is the leading cause of end-stage renal disease (ESRD) worldwide,
accounting for 42% of all patients on renal replacement therapy (RRT) in the
United States.2 The magnitude of this problem has continued to grow in the face
of an inexorable rise in the number of diabetic patients. The search for
therapeutic modalities to stem this tide remains the quest of many nephrologists.
One of the hallmarks of DN is increased urinary protein excretion, and
microalbuminuria has long been proposed as an early manifestation of this
disease.3,4 Albuminuria and chronic kidney disease (CKD) are strong determinants
of cardiovascular disease and to a large extent, the survival of patients with DN
is determined by cardiovascular morbidity. Although there remains no cure at
present, treatment options to prevent or slow disease progression are available.
In this update, we aim to address the current armamentarium in the management of
DN.
PMID- 24350319
TI - Psoriasis.
AB - Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting 1.3
2.2% of the UK population.1 Most commonly, psoriasis is characterised by well
demarcated, red plaques with adherent scale with a predilection for the scalp and
extensor surfaces of the limbs. However, the effects of psoriasis go far beyond a
patient's skin and may result in a degree of disability and impaired quality of
life similar to that of other major medical conditions, such as cancer and heart
disease. First-line therapies for most patients are topical treatments such as
topical corticosteroids and vitamin D analogues. For those with more severe or
treatment-resistant disease, second- or third-line therapies include
phototherapy, systemic therapies such as methotrexate and more recently biologic
therapies such as tumour necrosis factor (TNF) inhibitors. These therapeutic
modalities are proven to be highly effective; however, the potential for long
term toxicity needs to be considered. Aside from the visible skin disease,
psoriasis is also increasingly recognised to have important systemic
manifestations. Psoriatic arthritis has long been established as an associated
condition and, more recently, it has emerged that psoriasis is also associated
with an increased risk of inflammatory bowel disease, cardiovascular disease and
the metabolic syndrome. Both National Institute for Health and Care Excellence
(NICE)2 and Scottish Intercollegiate Guidelines Network (SIGN)3 have recently
published guidelines for the assessment and management of psoriasis which
highlight the need for regular assessment in order to detect the development of
arthritis and the presence of other co-morbidities such as obesity, diabetes,
dyslipidaemia and hypertension.
PMID- 24350320
TI - Predicting and preventing avoidable hospital admissions: a review.
AB - The strongest risk factors for avoidable hospital admission are age and
deprivation but ethnicity, distance to hospital, rurality, lifestyle and
meteorological factors are also important, as well as access to primary care.
There is still considerable uncertainty around which admissions are avoidable. In
terms of services to reduce admissions there is evidence of effectiveness for
education, self-management, exercise and rehabilitation, and telemedicine in
certain patient populations, mainly respiratory and cardiovascular. Specialist
heart failure services and end-of-life care also reduce these admissions.
However, case management, specialist clinics, care pathways and guidelines,
medication reviews, vaccine programmes and hospital at home do not appear to
reduce avoidable admissions. There is insufficient evidence on the role of
combinations or coordinated system-wide care services, emergency department
interventions, continuity of care, home visits or pay-by-performance schemes.
This highlights the importance of robust evaluation of services as they are
introduced into health and social care systems.
PMID- 24350321
TI - The 1918-19 influenza pandemic revisited.
AB - The worldwide influenza outbreak of 1918-19 was a medical catastrophe, causing
the deaths of around 50 million people. There is evidence however that the major
wave, in November 1918, was not part of the pandemic that started in the summer
of 1918. The virus responsible for the major wave has been isolated but the
structural features responsible for its severity remain incompletely understood.
In 1918-19 influenza was an infection so little understood that the government
was unsure of what action to take. In contrast, during the pandemic starting in
2009, international and national bodies used many means of communication to keep
the public fully informed, with beneficial results. In addition, antiviral
agents, a vaccine and antibiotics to treat secondary infection were available.
Such a response is possible only with appropriate funding and a comprehensive
medical infrastructure, making the potential outbreak of severe influenza in a
poor part of the world a matter of grave concern.
PMID- 24350322
TI - Henry VIII, McLeod syndrome and Jacquetta's curse.
AB - The mental decline of King Henry VIII from being a jovial, charismatic and
athletic young man into an increasingly paranoid, brutal tyrant in later life,
ever more concerned at his lack of one or more male heirs, has attracted many
medical diagnostic theories. Previous hypotheses have included diabetes, syphilis
and hypothyroidism, among others. However, these inadequately explain Henry's
failure to produce a male heir, despite multiple pairings. The latest postulated
diagnoses for Henry are the coexistence of both Kell blood group antigenicity
(possibly inherited from Jacquetta Woodville, Henry's maternal great grandmother)
causing related impaired fertility, and McLeod syndrome, causing psychotic
changes. As the mutated McLeod protein of the syndrome significantly reduces the
expression, effectively inactivating the Kell antigen, we critically review this
theory, examining in detail the pathophysiology of these conditions and assessing
the genealogy of Henry VIII and its effect in subsequent generations.
PMID- 24350323
TI - James Taylor (1859-1946): favourite disciple of Hughlings Jackson and William
Gowers.
AB - In neurological circles today the name James Taylor (1859-1946) is probably
remembered mainly for his role in editing the Selected Writings of John Hughlings
Jackson, the most readily available source of Jackson's contributions to
neurological knowledge. Taylors' own neurological achievements are largely or
entirely forgotten, but in his day he was an influential figure whose career
linked the great figures of the golden era of late nineteenth century British
neurology to the neurology of the first half of the twentieth century. Not only
was he a junior professional colleague and close friend of both John Hughlings
Jackson and William Gowers, he also produced a substantial corpus of neurological
writings in his own right, including a textbook of child neurology and the first
English language account of subacute combined degeneration of the spinal cord.
PMID- 24350324
TI - The eclipse and rehabilitation of JJR Macleod, Scotland's insulin laureate.
AB - John JR Macleod (1876-1935,) an Aberdonian Scot who had emigrated to North
America, shared the 1923 Nobel Prize with Frederick Banting for their discovery
of insulin at the University of Toronto in 1921-22. Macleod finished his career
as Regius Professor of Physiology at the University of Aberdeen from 1928 to
1935. Macleod's posthumous reputation was deeply tarnished by the campaigns
against him carried out by his fellow laureate, Banting, and by Banting's student
assistant during the insulin research, Charles Best. Banting's denigration of
Macleod was based on their almost total personality conflict; Best's was based on
a hunger for personal recognition. New research indicates how scarred both men
were in their obsessions. The rehabilitation of Macleod's reputation, begun in
1982 with my book, The Discovery of Insulin, has continued in both scholarly and
popular circles. By 2012, the ninetieth anniversary of the discovery of insulin,
it had become complete both at the University of Toronto and in Canada.
PMID- 24350325
TI - Peter Lowe's Whole course of chirurgerie... 1597.
PMID- 24350326
TI - Diagnosing the dead.
PMID- 24350327
TI - Fluorescence sensor for Cu(II) in the serum sample based on click chemistry.
AB - Cu(II) can be reduced to Cu(I) by sodium ascorbate (SA) in situ, which in turn
induces CuAAC reaction between the weak fluorescent compound (3-azido-7
hydroxycoumarin) and propargyl alcohol to form a strong fluorescent compound.
Based on such principle, a simple and sensitive fluorescence sensor for Cu(II)
can be developed, which combines the character of high selectivity of click
chemistry and high sensitivity of fluorescence detection. The value of
fluorescence increase factor shows a good linear relationship with the
concentration of Cu(II) in the range of 0.25 MUM-2.5 MUM with a detection limit
of 0.08 MUM. In addition, the developed sensor shows high selectivity towards
Cu(II) assay even in the presence of other common metal ions and it has been
successfully applied to detect Cu(II) in human serum with satisfactory results.
PMID- 24350328
TI - ATR-FTIR spectroscopy as a tool to probe surface adsorption on nanoparticles at
the liquid-solid interface in environmentally and biologically relevant media.
AB - Given the importance of nanoparticle surface composition in nanotoxicology,
analytical tools that can probe nanoparticle surfaces in aqueous media are
crucial but remain limited. Attenuated total reflectance Fourier transform
infrared (ATR-FTIR) spectroscopy is a technique capable of in situ
characterization of the liquid-solid interface to probe surface adsorption on
nanoparticle surfaces in environmentally and biologically relevant media.
Furthermore, given that the interfacial region in these media is dynamic, ATR
FTIR spectroscopy facilitates monitoring these dynamics by interrogating a layer
of immobilized nanoparticles coated on the ATR element while changing the
overlying aqueous phase. The molecular information acquired from this technique
allows for the determination of the adsorption mode, including conformational and
structural changes of the coordinating ligand, and can directly measure ligand
displacement reactions. Furthermore, in some cases, ATR-FTIR spectroscopy can be
used as a quantitative surface analytical tool. In this article, we briefly
review the fundamentals of the technique and then provide several examples of
using ATR-FTIR spectroscopy to probe nanoparticle surfaces in general with
respect to: (i) the adsorption of different environmentally and biologically
relevant coordinating ligands; (ii) competitive ligand adsorption and; (iii) the
determination of kinetic and thermodynamic parameters. We have also investigated
surface adsorption of TiO2 nanoparticles in different biological media typically
used for toxicity studies and show that the surface composition of TiO2
nanoparticles depends to a large extent on the composition of the medium due to
surface adsorption. This result has important implications for the interpretation
of toxicity data as well as inter-comparisons between toxicity studies.
PMID- 24350329
TI - Negative area compressibility in silver(I) tricyanomethanide.
AB - The molecular framework Ag(tcm) (tcm(-) = tricyanomethanide) expands continuously
in two orthogonal directions under hydrostatic compression. The first of its
kind, this negative area compressibility behaviour arises from the flattening of
honeycomb-like layers during rapid pressure-driven collapse of the interlayer
separation.
PMID- 24350330
TI - Creation of artificial cellulosomes on DNA scaffolds by zinc finger protein
guided assembly for efficient cellulose hydrolysis.
AB - For the first time, artificial cellulosome structures were created on DNA
scaffolds based on zinc finger protein (ZFP)-guided assembly. These resulting two
component cellulosome structures exhibited enhancement in cellulose hydrolysis
compared to the non-complexed mixture depending on the number of CBMs and
cellulases assembled.
PMID- 24350331
TI - New porphyrin derivatives for phosphate anion sensing in both organic and aqueous
media.
AB - New porphyrin-based anion receptors have been prepared from meso
tetrakis(pentafluorophenyl)porphyrin () and diamine derivatives. These receptors
(compounds ) interact preferentially with phosphate anions both in organic
solutions and in basic aqueous media when coated on gold piezoelectric quartz
crystals. A single crystal X-ray structure of the bis-HF complex of a imine
derivative of was obtained; it serves to highlight the main interactions between
the anion and cation receptors in the solid state.
PMID- 24350332
TI - High rate sodium ion insertion into core-shell nanoparticles of Prussian blue
analogues.
AB - We demonstrate that core-shell nanoparticles consisting of two different Prussian
blue analogues, one high capacity and the other robust, can provide enhanced rate
capability as cathode materials in sodium-ion batteries.
PMID- 24350333
TI - Tadpole pupil.
PMID- 24350334
TI - Practice patterns for intraoperative neurophysiologic monitoring.
PMID- 24350336
TI - Proceedings of the Third Annual RECOMB Satellite Workshop on Massively Parallel
Sequencing (RECOMB-seq 2013), April 11-12, 2013, Beijing, China.
PMID- 24350335
TI - Coordinating unspecified living kidney donation and transplantation across the
blood-type barrier in kidney exchange.
AB - BACKGROUND: This article studies multicenter coordination of unspecified living
kidney donation and transplantation across the blood-type barrier in kidney
exchange. Important questions are whether such coordination should use domino
paired donation or non simultaneous extended altruistic donor chains, what the
length of the segments in such chains should be, when they should be terminated,
and how much time should be allowed between matching rounds. Furthermore, it is
controversial whether the different modalities should be coordinated centrally or
locally and independently. METHODS: Kidney exchange policies are simulated using
actual data from the Dutch national kidney exchange program. Sensitivity analysis
is performed on the composition of the population, the time unspecified and
bridge donors wait before donating to the wait list, the time between matching
rounds, and donor renege rates. RESULTS: Central coordination of unspecified
donation and transplantation across the blood-type barrier can increase
transplants by 10% (PG0.001). Especially highly sensitized and blood type O
patients benefit. Sufficient time between matching rounds is essential: three
monthly exchanges result in 31% more transplants than weekly exchanges. Benefits
of non simultaneous extended altruistic donor chains are limited in case of low
numbers of highly sensitized patients and sufficient unspecified donors. Chains
are best terminated when no further segment is part of an optimal exchange within
3 months. CONCLUSIONS: There is clear synergy in the central coordination of both
unspecified donation and transplantation across the blood-type barrier in kidney
exchange. The best configuration of a national program depends on the composition
of the patient Y donor population.
PMID- 24350337
TI - Proceedings of the 11th OESO World Conference: Reflux disease, September 1-4,
2012, Como, Italy.
PMID- 24350338
TI - Reply to Boslough et al.: Decades of comet research counter their claims.
PMID- 24350339
TI - Reply to Subramaniam, van Heel, and Henderson: Validity of the cryo-electron
microscopy structures of the HIV-1 envelope glycoprotein complex.
PMID- 24350340
TI - Reply to Coyne: Genomic analyses are unthwarted.
PMID- 24350342
TI - Proceeding of the Challenges in Environmental Science and Engineering, CESE-2012:
September 9-13, 2012, Melbourne, Australia.
PMID- 24350341
TI - This issue is dedicated to the memory of Professor Norman B. Hecht.
PMID- 24350343
TI - Proceedings of the Chinese-Canada Symposium in Atherosclerosis and Cardiovascular
Disease, September 23-25, 2011, Beijing, China.
PMID- 24350344
TI - Special issue dedicated to Norman Letvin.
PMID- 24350345
TI - Proceedings of the 15th Congress of the ESVCN, 14 - 16 September 2011, Zaragoza,
Spain.
PMID- 24350347
TI - Proceedings of the 3rd EAO Consensus Conference, 15-18 February 2012, Pfaffikon,
Schwyz, Switzerland.
PMID- 24350346
TI - Proceedings of the Ninth International Conference on Information Processing in
Cells and Tissues (IPCAT), March 31-April 2, 2012, Cambridge, England.
PMID- 24350348
TI - FUS: a putative biomarker for essential tremor raised by whole-exome sequencing
analyses.
PMID- 24350349
TI - Genetic biomarkers of essential tremor: time to think outside of the box.
PMID- 24350351
TI - The role of fibroblast growth factor 21 in controlling reproduction during
nutritional deprivation.
PMID- 24350352
TI - My name is nobody.
PMID- 24350353
TI - Computing: Out of the hood.
PMID- 24350355
TI - Protecting health-care workers in the firing line.
PMID- 24350354
TI - WHO AFRO: looking for a leader.
PMID- 24350356
TI - 21st-century oncology: a tangled web.
PMID- 24350357
TI - Colorectal-cancer incidence and mortality after screening.
PMID- 24350358
TI - Explaining radiation risks to patients.
PMID- 24350359
TI - Principles of radiotherapy.
PMID- 24350360
TI - Clubbing.
PMID- 24350361
TI - Management of acute toxicity associated with radiotherapy.
PMID- 24350362
TI - [Therapy refractory compulsive disorders and psychosocial interventions at the
psychiatric institute outpatient service of the Leipzig University Clinic].
PMID- 24350363
TI - [Decision for collaborative pathway of care: ergotherapy in dialectical
behavioral therapy].
PMID- 24350364
TI - Reply: To PMID 22889743.
PMID- 24350365
TI - [Naming and packaging of pharmaceutical products].
PMID- 24350366
TI - Reply: To PMID 22889743.
PMID- 24350367
TI - [Interview by Anne-Katrin Dobler].
PMID- 24350368
TI - Developmental biology: Support mothers to secure future public health.
PMID- 24350370
TI - Failure of care.
PMID- 24350369
TI - Bibliometrics: global gender disparities in science.
PMID- 24350371
TI - The patent bargain.
PMID- 24350372
TI - Gender progress (?).
PMID- 24350373
TI - Author reply: To PMID 23522699.
PMID- 24350375
TI - Media highlights.
PMID- 24350374
TI - Twin research reports.
PMID- 24350376
TI - Retraction note to: Intestinal microbiota, probiotics and human gastrointestinal
cancers.
PMID- 24350377
TI - In the production of knowledge in Occupational Health it is necessary to be
committed.
PMID- 24350378
TI - Degloving injuries of the abdominal wall.
AB - OBJECTIVE: To stress the local, regional and global impact of degloving injuries
of abdominal wall based on which the surgeon can design the management protocol.
METHOD: A retrospective series of seven cases who met with high velocity run-over
accidents between the year 2002 to 2007. All patients were clinically examined
and the findings confirmed radiologically, which guided the management. RESULTS:
Out of the seven patients treated, six survived. All patients had open degloving
injury of abdominal wall and in different areas of the lower limbs, while three
had an additional closed degloving in the back, thighs and gluteal regions. All
of them had pelvic fractures of various types. Three patients had peritoneal
injury, of whom one had additional diaphragmatic injury. None of them had hollow
viscus perforation or injury to solid viscera despite the varied severity of
injuries to the abdominal wall, pelvic bone and diaphragm. CONCLUSION: Degloving
injuries of the abdominal wall are rarely encountered in our practice. The
associated morbidity and mortality are very high. However, the prognosis can be
improved by successful revival and rehabilitation of these patients, which is
possible by early resuscitation, recognition of all bony and soft tissue
injuries, early debridement and coverage.
PMID- 24350379
TI - ["Magic" oil to treat lice infestations].
PMID- 24350380
TI - [Not Available].
PMID- 24350381
TI - [Not Available].
PMID- 24350382
TI - No informed consumers without price transparency.
PMID- 24350383
TI - New immunotherapies for cancer yield exciting results but high cost.
PMID- 24350384
TI - Next-generation cancer biologics shine in studies.
PMID- 24350385
TI - United States obesity, overweight rates to soar.
PMID- 24350388
TI - [Diagnosis of a giant abdominal nodule triggered by abdominal pain].
PMID- 24350390
TI - An investigation of Salmonella Typhimurium linked to contaminated eggs on the
Central Coast of NSW, 2008.
PMID- 24350389
TI - Cholinergic efferent synaptic transmission regulates the maturation of auditory
hair cell ribbon synapses.
AB - Spontaneous electrical activity generated by developing sensory cells and neurons
is crucial for the maturation of neural circuits. The full maturation of
mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous
action potentials during a 'critical period' of development. The intrinsic
spiking activity of IHCs can be modulated by inhibitory input from cholinergic
efferent fibres descending from the brainstem, which transiently innervate
immature IHCs. However, it remains unknown whether this transient efferent input
to developing IHCs is required for their functional maturation. We used a mouse
model that lacks the alpha9-nicotinic acetylcholine receptor subunit
(alpha9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent
terminals to remove or reduce efferent input to IHCs, respectively. We found that
the efferent system is required for the developmental linearization of the Ca(2+)
sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their
general cell development. This provides the first direct evidence that the
efferent system, by modulating IHC electrical activity, is required for the
maturation of the IHC synaptic machinery. The central control of sensory cell
development is unique among sensory systems.
PMID- 24350391
TI - Secondary service connection for diagnosable illnesses associated with traumatic
brain injury. Final rule.
AB - The Department of Veterans Affairs (VA) amends its adjudication regulations
concerning service connection. This final rule acts upon a report of the National
Academy of Sciences, Institute of Medicine (IOM), Gulf War and Health, Volume 7:
Long-Term Consequences of Traumatic Brain Injury, regarding the association
between traumatic brain injury (TBI) and five diagnosable illnesses. This
amendment establishes that if a veteran who has a service-connected TBI also has
one of these diagnosable illnesses, then that illness will be considered service
connected as secondary to the TBI.
PMID- 24350392
TI - Patient Protection and Affordable Care Act; maximizing January 1, 2014 coverage
opportunities. Interim final rule with comment period.
AB - This interim final rule amends the date by which a qualified individual must
select a qualified health plan (QHP) through any Exchange for an effective
coverage date of January 1, 2014. This rule generally allows consumers to select
a QHP until December 23, 2013, which is a change from the previously stated
regulatory date of December 15, 2013, but permits State Exchanges to select a
different date. It also establishes a related policy regarding the date by which
a consumer needs to pay any applicable initial premium to ensure timely
effectuation of coverage. This rule pertains to the individual market and Small
Business Health Options Program in both the Federally-facilitated Exchanges and
State Exchanges. This rule does not change the plan selection or premium payment
dates for coverage offered outside of the Exchanges.
PMID- 24350393
TI - Nurse-led PICC insertion: is it cost effective?
AB - AIMS: Repeated attempts to cannulate small veins can cause considerable distress
for patients and expend substantial staff time.For longer term venous access, a
peripherally inserted central catheter(PICC) may be used instead of a peripheral
cannula. Previous studies indicate that insertion of a PICC costs three times
more than a cannula but the lifespan is substantially longer. This study aimed to
compare insertion cost, patient satisfaction, and infection rates of PICCs for
the two main staff groups (trained nurses and radiologists) inserting these
devices in a district general hospital. MATERIALS AND METHODS: The study took
place over 4 months in 2012-13.A questionnaire was attached to all identified
PICCs in stock at Raigmore Hospital to collect details of the date of insertion,
patient involved, time taken, attendant staff grade and experience
level,consumables used and insertion success. The lead author's personal
observation of PICC insertion by different staff groups allowed estimation of
staff time, costs and success rates. Patient experience and satisfaction was
assessed before and after insertion using a patient questionnaire. PICC
longevity, infection rates and failures were assessed by review of patient notes.
RESULTS: The radiologist group had a statistically significant (p< 0.01)
increased cost (42%) over the nurse group. Patient satisfaction regarding
explanation of treatment before insertion was higher in the nurse group.
Insertion success and infection rates were higher in the radiologist group.
CONCLUSION: The authors conclude that the majority of PICCs can be safely
performed without x-ray screening in a ward-based environment. This is likely to
be the most cost-effective solution for large volume services.
PMID- 24350395
TI - Use of winged infusion devices in intravenous therapy.
AB - This article has been written to highlight the licensed use of winged infusion
devices for short-term intravenous (IV) therapy. There is limited published
literature on the subject, yet this clinical audit has demonstrated that the use
of winged infusion devices has clear advantages for patients and nurses. The
audit was conducted in the community setting but could be replicated in any
community or hospital environment where short-term intravenous therapy of
nonvesicant fluids are administered. For the purpose of this audit, nonvesicant
antibiotics were administered.
PMID- 24350394
TI - Vascular access: viewing the vein.
PMID- 24350396
TI - Patients' experiences of community IV therapy.
AB - AIM: To explore patients' experiences of receiving community intravenous therapy
(CIVT) compared with traditional inpatient hospital care. METHOD: The study used
a qualitative descriptive methodology. Semi-structured interviews were conducted
with eight participants, transcribed verbatim and thematically analysed. RESULTS:
Five themes were identified: 'finances'; 'travelling'; 'hospital
admission';'being at home'; and 'safety'. DISCUSSION: The study revealed that
participants felt privileged and valued when they were treated at home.CIVT
allowed them the comfort of being in a familiar environment and the convenience
of doing what they wanted, when they wanted. CONCLUSION: This study concurs that
patients do prefer to be treated at home rather than being admitted to secondary
care. The findings from this study suggest that participants appreciated the
opportunity to receive CIVT.
PMID- 24350397
TI - Needle-free drug delivery.
PMID- 24350398
TI - Nuclear cardiology.
PMID- 24350399
TI - Physician assistants in dermatology.
PMID- 24350400
TI - Deep brain stimulation.
PMID- 24350401
TI - Clinical neurophysiology.
PMID- 24350402
TI - Physician assistants in orthopedic surgery.
PMID- 24350403
TI - Puzzles in practice. Arrhythmogenic right ventricular dysplasia (ARVD).
PMID- 24350404
TI - Hyperprolactinemia: a 12-year retrospective study at gynecologic endocrinology
unit, Siriraj Hospital.
AB - BACKGROUND: Hyperprolactinemia is one of the most common endocrine disorders of
the hypothalamic-pituitary axis. To date, no available data about
hyperprolactinemia in Thai women has been published OBJECTIVE: To determine
clinical and laboratory findings of Thai female patients with different etiology
of hyperprolactinemia, as well as the response of treatment, recurrence, and
pregnancy after treatment. MATERIAL AND METHOD: Medical records of 139 female
patients with the diagnosis of hyperprolactinemia in Gynecologic Endocrinology
Unit, Siriraj Hospital between January 1, 1999 and December 30, 2011 were
retrospectively reviewed after the study protocol was approved by Siriraj
Institutional Review Board. The data was analyzed to determine patient
demographic data, presenting symptoms, duration of symptoms, initial serum
prolactin levels, causes, imaging studies, treatment, treatment outcomes, and
adverse events. RESULTS: Ninety-seven female patients with hyperprolactinemia
were included in the study. Mean age at diagnosis was 31.8 +/- 7.7 years.
Amenorrhea was the most common presenting symptom (49.5%) followed by
galactorrhea (44.3%). Median initial serum prolactin level was 117 ng/mL (25.1
1,624 ng/mL). Pituitary adenoma is the most common cause (40.2%) followed by
idiopathic hyperprolactinemia (37.1%). Microadenomas were found in 74.3% of
pituitary adenoma. The median size of the tumor was 9 mm. Medical treatment was
given to 79 (88.8%) patients. Bromocriptine was given to 66 patients. Mean of
maximum dose of bromocriptine was 5.8 mg. Median duration of treatment was 35.8
months. Adverse events were reported in 24.2% of patients, dizziness was the most
common adverse event. Median time to normalize serum prolactin level was 3.8
months. In 29 patients who desired pregnancy, eight patients got pregnant. Median
time to pregnancy was 25.9 months. Patients with macroadenoma had significantly
higher prolactin level than those with microadenoma (p = 0.024). Patients with
galactorrhea had the shortest duration of symptom (p = 0. 010). There were no
statistically significant difference in symptoms, duration of symptoms, and
initial prolactin level between patients with and without pituitary adenoma.
Patients with pituitary adenoma needed higher doses (p = 0.009) and longer
duration of treatment (p = 0.007) than those without a tumor Normalization of
prolactin level and recurrence rate was not different between the two groups (p =
0.056 and 0.374). Log rank test showed that the time to normalize and survival
time of recurrence were not significantly different between patients with and
without a tumor (p = 0.136 and 0.146, respectively). CONCLUSION: Amenorrhea was
the most common presenting symptom in Thai hyperprolactinemic females, who
attended Siriraj gynecologic endocrinology unit, followed by galactorrhea.
Pituitary adenoma is the most common cause followed by idiopathic
hyperprolactinemia. Patients with pituitary adenoma needed higher doses and
longer duration of treatment than those without a tumor
PMID- 24350405
TI - Efficacy of dietary modification following the National Cholesterol Education
Program (NCEP) recommendation on lipid profiles among hyperlipidemia subjects.
AB - BACKGROUND: Hyperlipidemia has adverse effects on atherosclerosis, causing it to
develop into cardiovascular disease. The prevalence of hyperlipidemia has been
increasing among those in the working-age group and may be caused by
inappropriate dietary patterns. Dietary modification should form the basis of
lipid management. OBJECTIVE: Evaluate the effects of a dietary modification
following the NCEP-ATP III recommendation on lipid profiles among hyperlipidemia
subjects. MATERIAL AND METHOD: The design was a quasi-experimental study, with a
pre-test/post-test two-group design. Each group consisted of 31 hyperlipidemia
subjects aged 30 to 59 years old with total cholesterol (TC) greater than or
equal to 240 mg/dl or low-density lipoprotein cholesterol (LDL-C) greater than or
equal to 130 mg/dl. The present study was conducted between January and June
2009. The research procedure included 6-week nutrition counseling and a 2-week
follow-up for 12 weeks. Data were collected by self-reported questionnaire and a
3-day food record. Dietary and biological assessments were compared before and
after the experiment. Statistical analysis was performed using means, standard
deviations, independent and paired t-tests, Friedman test, Mann-Whitney U test,
and Wilcoxon signed-rank test. RESULTS: The intervention group had a significant
reduction of TC and LDL-C at the end of the experiment (p < 0.05). Moreover this
group had a significantly higher percentage reduction of TC and LDL-C than the
control group (8.5% vs. 3.0%, and 10.8% vs. 2.4%, respectively) (p < 0.05).
Distributions of monounsaturated fatty acids (MUFAs) in the intervention group
were significantly higher than in the control group (p < 0.05). Distribution of
saturated fatty acids (SFAs):MUFAs:polyunsaturated fatty acids (PUFAs) were
12.0:13.4:6.3% in the intervention group and 12.3:9.2:5.6% in the control group.
Neither group was able to reduce SFAs intake to < 7% as recommended. Neither the
recommended one-third of vegetable protein nor two-thirds of complex carbohydrate
was achieved Dietary fiber was less than 10 g/1,000 kcal. The cholesterol intake
in the intervention group was less than in the control group (155.9 vs. 206.3
mg/d). CONCLUSION: The dietary modification in the present study significantly
lowered TC and LDL-C. However compliance with the recommendation of high MUFAs
intake was difficult to achieve. The dietary modification might be focused
instead on lowering intake of SFAs, replacing animal protein with vegetable
protein, and increasing complex carbohydrates, fruits, and vegetables to raise
dietary fiber.
PMID- 24350406
TI - Electrolytes imbalance in saltwater near-drowning victims in the Gulf of
Thailand.
AB - BACKGROUND: Near-drowning victims in saltwater are expected to have multiple
electrolytes imbalance that affected treatment outcome. There are limited data
about these parameters in Thailand to guide the treatment plan. OBJECTIVE: To
study the characteristic of electrolytes imbalance in saltwater near-drowning
victims in the Gulf of Thailand. MATERIAL AND METHOD: Retrospective analytic
study of 39 medical records of near-drowning patients admitted to Burapha
University Hospital between 2000 and 2010. Characteristics of the patients and
serum electrolytes were analyzed by SPSS version 19 for windows. RESULTS: The
study included 23 male, 16 female patients. Average age was 14.46 +/- 11.15 years
and 19/39 (48.72%) patients were aged 10 or less. The following electrolytes
imbalance were identified, hypokalemia 8/39 (20.51%), hypernatremia 12/39
(30.77%), hyperchloremia 15/39 (38.46%), high anion gap 23/39 (58.97%), and
hypobicarbonatemia 28/39 (71.79%). Seven out of eight patients in the hypokalemia
group were in the high anion gap group. Mean SpO2 in the patients who had high
anion gap was significantly lower than those who had normal anion gap (87.06 +/-
17.68% vs. 95.8 +/- 5.94% p = 0.031) without difference in systolic blood
pressure (112.59 +/- 14.63 vs. 105.67 +/- 13.98 p = 0.159). Those who were
hypotensive significantly had lower bicarbonate (17.00 +/- 3.51 vs. 20.59 +/-
3.81 p = 0.038) and higher anion gap (19.29 +/- 1.799 vs. 16.25 +/- 6.25 p =
0.025) than normotensive patients. CONCLUSION: Hypobicarbonatemia, high anion
gap, hypernatremia, and hypokalemia were common in saltwater near-drowning
patients in the Gulf of Thailand. The cause of high anion gap was probably due to
hypoxia and hypotension.
PMID- 24350407
TI - Outcomes of MDR/XDR-TB patients treated with linezolid: experience in Thailand.
AB - BACKGROUND: Multi-drug-resistant/extensively drug-resistant tuberculosis (MDR/XDR
TB) becomes an increasing problem in management. Linezolid has been off-label
used in treatment of MDR/XDR-TB with major adverse effects. OBJECTIVE: To study
outcomes of MDR/XDR-TB patients treated with linezolid in Central Chest Institute
of Thailand. MATERIAL AND METHOD: MDR/XDR-TB patients treated with linezolid from
2009-2012 were retrospective analyzed RESULTS: Seventeen from 24 cases had
finished treatment. Linezolid, capreomycin, cycloserine, clofazimine,
moxifloxacin, ethambutol, kanamycin, ethionamide, and PAS were used in 24, 21, 8,
7, 5, 5, 2, 2, and 2 cases respectively. Long-term injection of capreomycin was
used in 14/17cases for an average of 14.7 months. Three point three drugs were
used as an average. Average conversion time of smear and culture were 53.5 and
52.1 days respectively Treatment time averaged 19.1 months. Fifteen of 24 cases
were cured, seven were still ongoing treatment, all had sputum culture
conversion, and two cases failed. There was no relapse in 13 cases after a follow
up that averaged 10.6 months. Linezolid was stopped in five cases from peripheral
or optic neuropathy. Capreomycin was stopped in four cases from vestibulotoxic
and nephrotoxic. CONCLUSION: Linezolid has good efficacy in treatment of MDR/XDR
TB with major adverse effect and should be used with caution. If capreomycin is
susceptible or likely active, long-term injection should be considered when
likely active drugs are not enough to strengthen the regimen.
PMID- 24350408
TI - Pharmacodynamics of meropenem in critically ill patients with ventilator
associated pneumonia.
AB - BACKGROUND: Pharmacokinetic changes have been found in critically ill patients,
including ventilator-associated pneumonia (VAP) when compared with healthy
volunteers leading to fluctuation of plasma concentrations. OBJECTIVE: To compare
the probability of target attainment (PTA) and cumulative fraction of response
(CFR) for meropenem between administration by a bolus injection and a 3-hour
infusion. MATERIAL AND METHOD: The study was a randomized three-way crossover in
nine patients with VAP. Each patient received meropenem in three regimens
consecutively: (i) a bolus injection of 1 g every eight hours (q8h) for 24 hours;
(ii) a 3-hour infusion of 1 g q8h for 24 hours; and (iii) a 3-hour infusion of 2
g q8h for 24 hours. The pharmacodynamic analysis of meropenem was performed to
determine the PTA by using the Monte Carlo simulation and the study used
susceptibility patterns obtained from EUCAST and MYSTIC for assessment of CFR.
RESULTS: For an MIC of 4 microg/ml, the PTAs achieving 40% T > MIC following a
bolus injection of 1 g q8h, a 3-hour infusion of 1 g q8h, and a 3-hour infusion
of 2 g q8h were 87.71%, 98.80%, and 99.90%, respectively. Only the 3-hour
infusion regimens were predicted to achieve a CFR > or = 90% against E. coli,
Klebsiella spp., P. aeruginosa, and Acinetobacter spp. CONCLUSION: A 3-hour
infusion of 2 g of meropenem regimen was predicted to have the highest PTA rates.
Only the prolonged infusion regimens achieved a high CFR against E. coli,
Klebsiella spp., P. aeruginosa, and Acinetobacter spp.
PMID- 24350409
TI - Prevalence, clinical manifestations and mortality rate in patients with
spontaneous pneumothorax in Thammasat University Hospital.
AB - BACKGROUND: Spontaneous pneumothorax (SP) can be a medical emergency requiring
early diagnosis and treatment to prevent subsequent respiratory failure and
death. SP epidemiologic and clinical data are limited in Thailand OBJECTIVE: To
study the prevalence, clinical manifestations, and mortality rate of SP in Thai
patients. MATERIAL AND METHOD: A retrospective case study was conducted between
July 2004 and December 2010 in patients with a confirmed diagnosis of SP
Demographic, etiologic, clinical, radiographic, and outcome data were collected.
RESULTS: One hundred patients with SP were identified (66 primary, 34 secondary
SP), for a prevalence of 76.3 per 100,000 hospital admissions. Males numbered 83.
Male to female ratios were 7.5:1 and 4.1:1 for primary and secondary SP
respectively. Mean (+/- standard deviation) age and body mass index were 35.3 +/-
20.3 years and 18.0 +/- 2.2 kilogram/meter2. The common presenting symptoms were
dyspnea (73%), chest pain or discomfort (68%), pleuritic pain (46%), cough (20%),
and fever (13%). Causes of secondary SP were pulmonary tuberculosis (19/34,
55.9%), chronic obstructive pulmonary disease (14/34, 41.2%), and pneumonia
(8/34, 23.5%). There were 12 deaths (12%), 11 with secondary SP CONCLUSION:
Spontaneous pneumothorax was relatively common with typical clinicalfeatures.
Almost all of mortality cases rate suffered secondary SP Prospective studies are
needed to develop evidenced based algorithms, especially for secondary SP
patients.
PMID- 24350410
TI - Prevalence of coronary artery disease in different ethnic groups at a tertiary
care hospital.
AB - OBJECTIVE: To compare the prevalence of coronary artery disease (CAD) between
Thai Muslim and Thai Buddhist patients. MATERIAL AND METHOD: A hospital based
retrospective study was carried out to investigate the prevalence of CAD and
cardiovascular risk factors of these two ethnic and religious groups at Nopparat
Rajathanee Hospital between June 2012 and December 2012. All Thai Muslim patients
aged > or = 35 years who visited the internal medicine outpatient department
(OPD) were studied. The compared population was randomly selected and matched by
age and sex from the Thai Buddhist patients in the same period RESULTS: Five
hundred seventy nine patients with median age of 62 years (interquartile range =
24) were studied. There were 289 Thai Muslims and 290 Thai Buddhists. The
prevalence of definite CAD in Muslims (14.20%) was significantly higher than the
prevalence in Buddhists (6.2%) (p = 0.002). The prevalence of diabetes mellitus,
hypertension, high total cholesterol (> or = 240 mg/dl), and high triglyceride in
Muslims were significantly higher For high-density lipoprotein cholesterol (HDL
C), only Muslim females showed significantly higher prevalence of low HDL-C than
that of Buddhist females. CONCLUSION: Thai Muslims showed significantly higher
prevalence of definite CAD than that of Thai Buddhists. The greater prevalence of
certain risk factors may contribute to higher prevalence of CAD in Thai Muslim
patients.
PMID- 24350411
TI - Spontaneous craniocervical arterial dissection: a clinical and vascular
neuroimaging study.
AB - BACKGROUND: Spontaneous craniocervical arterial dissection (SCAD) is an important
cause of stroke in the young and middle-aged population. However clinical data of
SCAD is limited in Thailand. This present study aims to describe the clinical
profiles of SCAD in a tertiary care center in Thailand. MATERIAL AND METHOD: All
SCAD patients admitted to King Chulalongkorn Memorial Hospital between January
1997 and October 2011 were enrolled. All of the patients fulfilled vascular
imaging diagnostic criteria for SCAD. Clinical profiles, associated risk factors,
vascular neuroimaging patterns, treatments, and outcomes were analyzed by SPSS
program version 17. RESULTS: Fifty patients with SCAD were identified (0.5% of
total hospitalized ischemic cerebrovascular disease and subarachnoid hemorrhage
(SAH) patients). SCAD was found in 1.6% of patients under the age of 45 years.
Eighty-six percent of the patients were diagnosed during the last five years of
this present study period. Internal carotid artery dissection (ICAD) and
vertebral artery dissection (VAD) were detected in 42% and 58% respectively. The
mean age was 48.3 +/- 15.3 years. Atherosclerotic risk factors included
hypertension (16%), diabetes mellitus (24%), and dyslipidemia (28%). History of
previous minor head injury and migraine were encountered in 8% and 4%
respectively. Headache was detected in 80% of the cases. Localized headache was
observed in 64% of the cases. Diffuse headache due to SAH was detected in 14% of
the cases. Neurological syndromes at presentation were ischemic stroke (72%),
transient ischemic attack (TIA) (80%), and SAH (16%). Pathognomonic vascular
neuroimaging patterns of dissection included wall hematoma (36%), flame-shaped
appearance (28%), dissecting pseudoaneurysm (24%), and intimal flap (8%). Other
vascular imaging features included dissecting vessel stenosis (58%) and
dissecting vessel occlusion (18%). Treatment consisted of anticoagulants (60%),
antiplatelets (10%), surgical intervention (22%), and conservative management
(8%). Neurological outcomes at discharge with MRS 0-3 were 72%. No recurrent
dissection or recurrent cerebrovascular events were observed during the six-month
follow-up period In this present study, significant differences between ICAD and
VAD in terms of percentage of SAH, severity, and outcomes were observed
CONCLUSION: SCAD results in diverse cerebrovascular events such as ischemic
stroke, TIA, and SAH in the young and middle-aged population. Advances in
vascular neuroimaging play a crucial role in the diagnosis of SCAD. Prompt
management is essential for SCAD with a rather favorable outcome.
PMID- 24350412
TI - Allergic family history as a protective determinant to helminthic infection.
AB - OBJECTIVE: Investigate the resistance to helminths in children with an allergic
family history. MATERIAL AND METHOD: The study was undertaken as part of the
Prospective Cohort Study of Thai Children (PCTC) that followed all births in the
year 2001 from rural districts in Thailand. The family histories of allergic
diseases were validated by the physicians'diagnoses and medical record reviews.
Fresh stool examinations were carried out at 18 to 36 months of age. RESULTS: Of
1,076 live births in the cohort, 659 children had complete information. A family
history of allergy presented in 5.4% of the children. The prevalence of any
helminthic infection, Ascaris lumbricoides, Trichuris trichiura, and hookworm
were 25.0%, 18.2%, 9.2%, and 5.3%, respectively. The adjusted odds ratio of a
family history of allergy for helminthic infection was 0.28 (95% CI, 0.08-0.95).
CONCLUSION: A family history of allergic diseases independently increases
resistance to helminthic infection.
PMID- 24350413
TI - The impact of child's severity on quality-of-life among parents of children with
autism spectrum disorder: the mediating role of optimism.
AB - OBJECTIVE: Investigate the impact of child severity and optimism on quality-of
life in parents of children with Autism Spectrum Disorder (ASD). Additionally,
the role of optimism as mediator between child's severity and parental quality-of
life was also evaluated MATERIAL AND METHOD: Three hundred three parents of
children with ASD were recruited from the local autistic centers and schools in
Bangkok, Thailand. A set of demographic information sheet, the Childhood Autism
Rating Scale (CARS), the Life Oriented Test-Revised (LOT-R), and the WHOQOL-BREF
test were submitted for collecting parental information. RESULTS: Using Pearson
Correlation, a significant negative association was found between child's
severity and parental quality-of-life while optimism was found to correlate
positively with parental outcomes. The finding from path-analysis confirmed that
impairment of language and repetitive behavior of an ASD child associated with
optimism that, in turn, predicted level of parental quality-of-life in all
domains. CONCLUSION: The current findings assured a role of optimism as mediator
between child's severity and parental quality-of-life. Implications for the
development of intervention focused on enhancing parent's optimism were
recommended.
PMID- 24350414
TI - Effects of rapid response trauma team in thoracic injuries in northern trauma
center level I.
AB - BACKGROUND AND OBJECTIVE: Associated thoracic injury is the first priority at the
initial assessment and its outcomes are time-dependent. Faculty of Medicine,
Chiang Mai University organized a rapid response trauma team (RRTT) at mid-year
2006. The aims of this present paper were to report the effects of RRTT regarding
outcomes of thoracic injury. MATERIAL AND METHOD: We performed a retrospective
review for admitted thoracic injury patients between January 2004 and September
2009. The interval prior to July 2006 was defined as "before RRTT" and the latter
as "after RRTT". The severity-adjusted mortality was calculated. RESULTS: During
the 69 months, 951 patients were included (427 in "before RRTT", 524 in "after
RRTT"). Although the severity injury score (ISS) was significantly lower before
RRTT the severe trauma patients (ISS > 15) had a significantly higher mortality
(25.3% vs. 15.3%; p = 0.01). RRTTsignificantly improved the mortality odds ratio
in the overall and severe trauma [0.39 (0.22-0.68); p < 0.01 and 0.43 (0.25
0.73); p < 0.01]. Subgroup analysis found to have positive effects with the RRTT
in maxillofacial, head, and orthopedics associated injuries. CONCLUSION: RRTT for
thoracic injuries in the tertiary level I trauma center could decrease the
severity-adjusted mortality, especially in severe trauma patients.
PMID- 24350415
TI - Low molecular weight heparin prevents the progression of precollapse
osteonecrosis of the hip.
AB - BACKGROUND: Hypercoaguable state has been indicated as a major risk factor in
predisposing the idiopathic osteonecrosis of the hip. Furthermore, many studies
have demonstrated that low molecular weight heparin (LMWH) can reverse the
pathophysiology of the osteonecrosis of the hip in thrombophilic patients.
OBJECTIVE: Determine whether LMWH can prevent the progression of idiopathic
osteonecrosis of the hip. MATERIAL AND METHOD: A retrospective study of 36
patients who had bilateral idiopathic osteonecrosis with at least one hip in the
pre-collapsed stage (Ficat & Arlet stage I-II) was conducted. In the study group,
18 patients (26 hips) received 6,000 units of Enoxaparin daily for 12 weeks. In
the control group, 18 patients (23 hips) received no Enoxaparin. All patients
were given radiographic evaluations every three months for a minimum of24 months.
RESULTS: At the last follow-up, 15 hips (57.7%) from the study group and five
hips (21.7%) from the control group were observed to remain in the pre-collapse
stage (p = 0.042). Coagulation disorder was observed in seven patients (38.9%) of
the experimental group and five patients (27.8%) of the control group. One
patient from the study group exhibited hematuria with spontaneous resolution
after the course ofEnoxaparin injection. CONCLUSION: A progression rate of
idiopathic osteonecrosis of the hip from the pre-collapse stage to the collapsed
stage was found to be significantly lower in patients who received LMWH.
PMID- 24350416
TI - Efficacy of benzydamine hydrochloride dripping at endotracheal tube cuff for
prevention of postoperative sore throat.
AB - BACKGROUND: Postoperative sore throat (POST) is a frequent consequence following
ETT intubation, which may negatively affect the postoperative course and patient
satisfaction. Benzydamine hydrochloride is a topically-applied non-steroidal anti
inflammatory drug (NSAID). The authors evaluated the analgesic effect of
benzydamine hydrochloride dripping on the ETT cuff on POST. MATERIAL AND METHOD:
Eighty-six patients participated in this randomized controlled trial. They were
assigned into either the benzydamine hydrochloride or the control group. The
whole ETT cuff was dripped either with 3 ml (4.5 mg) of benzydamine hydrochloride
or nothing five minutes prior to anesthesia induction. The incidence and severity
of POST at 0, 2, 4, 6, 12 and 24 hours postoperatively were assessed. The
potential adverse effects of benzydamine hydrochloride (throat numbness throat
burning sensation, dry mouth, and thirst) were also evaluated. RESULTS: Twenty
five patients (58.14%) in each group had POST (p-value = 1). The severity of POST
(calculated from affected patients) in both groups at different time points was
not significantly different. Patients in the benzydamine hydrochloride group did
not have a higher incidence of adverse effects. CONCLUSION: We found that
dripping benzydamine hydrochloride on the ETT cuff neither reduced the incidence
of POST nor increased the incidence of adverse effects in comparison with no
intervention.
PMID- 24350417
TI - The improved quality process after implementation of the hemithyroidectomy care
map.
AB - OBJECTIVE: To report the improved quality process in service care of the patients
undergoing hemithyroidectomy and the results of the care map implementation.
MATERIAL AND METHOD: Descriptive analysis and retrospective chart reviews were
performed in the patients who underwent hemithyroidectomy in the Department of
Otorhinolaryngology, Faculty of Medicine Siriraj Hospital before and after the
care map implementation between January 2004 and December 2006. RESULTS:
Hemithyroidectomy care map has been created with good cooperation of all members
of our department in January 2005. Two hundred seventy nine patients, including
246 females (88%) and 33 males (12%) participated in this study. The care map was
used in all patients. Hospital stay was reduced from five to eight days to less
than four days in 93% of the patients. The estimated expenses of 97% of the
patients differed from the true expense at less than 20%. Complications were
minimized to the acceptable level by close supervision of the attending staffs.
Incidence of vocal cord paralysis was reduced from 8.7% before the care map
implementation to 2.4% and 2.3% in the first and second years. Hematoma was
observed in three cases within 24 hours postoperatively and could not be
prevented by drain insertion. Only minimal content was found in the drain after
48 hours. CONCLUSION: The improved quality process in hemithyroidectomy care
received good cooperation from all members in our department. Effective resource
utilization was achieved with maximal patients'benefit and satisfaction. Close
supervision by attending staffs, meticulous surgical techniques, and adequate
bleeding control are the keys of effective clinical care. Hospital stay is
possibly reduced to one to two days by good pre-anesthetic care before admission
and by avoiding or using drain only in selected cases for six to 48 hours.
PMID- 24350418
TI - The factors affecting quality of life in Thai psoriasis patients.
AB - OBJECTIVE: To identify the factors that affect quality of life in Thai psoriasis
patients. MATERIAL AND METHOD: Data collected from 326 psoriasis patients that
visited dermatology clinic at Siriraj Hospital, Bangkok, Thailand between 2001
and 2007 was used. Dermatology Life Quality Index (DLQI) was used to measure
quality of life. Severity was evaluated by Psoriasis Area and Severity Index
(PASI). RESULTS: Overall, psoriasis had moderate to very large negative effect on
the patient's life. There was a tendency that elderly patients had a slightly
better quality of life than younger adult and middle-age patients. However other
demographic variables (i.e., gender, occupation, and income) had no influence on
quality of life. This study also identified a linear trend of increased overall
DLQI with greater PASI. CONCLUSION: Only older age and lesser severity of disease
had association with few burdens in Thai psoriasis patients.
PMID- 24350419
TI - Cost-effectiveness analysis of 18F-FDG PET/CT in detecting suspected recurrence
or metastasis in well-differentiated thyroid carcinoma patients with negative
diagnostic total body scan in Thailand: a decision analysis.
AB - OBJECTIVE: To evaluate cost-effectiveness analysis of 18F-FDG PET/CT to detect
tumor recurrence or metastasis in well-differentiated thyroid cancer patients
with high Tg but negative TBS in Thailand. MATERIAL AND METHOD: A retrospective
literature review of 55 studies published between 1978 and 2010 was done.
Decision analysis by TreeAge program showed an evaluation of the most cost
effective treatment and 18F-FDG PET/CT scan in thyroid cancer patients with high
Tg but negative TBS. The incremental cost and life years gained associated with
seven strategies approached were analyzed by the decision tree model. The first
strategy was treatment with empirical high dose 131I therapy. The second to the
seventh strategies were using imaging investigations by CT scan of neck and
chest, 99mTc MIBI scan, and 18F-FDG PET/CT scan to identify recurrent,
persistent, and metastatic lesions before the specific treatment via curative
surgery, external radiotherapy, and high dose 131I therapy. All strategies were
adopted using hospital perspective and direct medical cost was estimated based on
the reference price of Siriraj Hospital. Deterministic sensitivity analysis was
conducted to investigate the effect of the cost of PET/CT scan. RESULTS: The
strategy using 18F-FDG PET/CT scan to detect recurrence or metastasis and
possible curative surgery in operable cases and high dose 131I therapy in
inoperable cases gave the highest life years gained of 27.08 with cost of
90,227.61 Baht (2,926.24 US dollars) and acceptable incremental cost
effectiveness ratio (ICER) of 6,936.88 Baht (224.98 US dollars) per life year
gained when compared to the least costly strategy using 99mTc MIBI scan and
additional 18F-FDG PET/CT scan in negative MIBI result. Other strategies were
dominated by this PET/CT strategy. Deterministic sensitivity analysis (based on
the willingness to pay (WTP) 360,000 Baht (11,675.42 US dollars) showed that the
cost of PET/CT scan has no impact on the net health benefit. CONCLUSION: Based on
the hospital perspective, the cost-effectiveness of 18F-FDG PET/CT scan in
detecting suspected recurrence or metastasis in thyroid carcinoma patients with
negative diagnostic TBS but high Tg was first done using 18F-FDG PET/CT scan to
identify disease, followed by curative surgery or high dose 131I therapy.
Moreover cost of PET/CT scan did not influence the net health benefit. This
PET/CT benefit is helpfulfor considering the proper PET/CT use for thyroid cancer
in Thailand.
PMID- 24350420
TI - Diagnostic performance of advanced MRI in differentiating high-grade from low
grade gliomas in a setting of routine service.
AB - OBJECTIVE: To evaluate the usefulness of advanced MRI techniques in
differentiating high-grade (HGG) from low-grade gliomas (LGG). MATERIAL AND
METHOD: Sixty-four patients with suspected gliomas were prospectively evaluated
by conventional and advanced MRI studies including MR spectroscopy (MRS),
diffusion tensor imagining (DTI), and dynamic susceptibility contrast (DSC) MRI.
The parametric measurements of metabolic profile, cerebral blood volume, flow
(CBV, CBF), apparent diffusion coefficient (ADC), fractional anisotropy, and
their ratios by internal normalization were analyzed to differentiate LGG from
HGG. Histopathologic findings were used as the gold standard. RESULTS: Forty
three cases with pathologically-proven gliomas were included The best
discriminating features between HGG and LGG were CBV and CBF of the solid tumoral
region (p < 0.05) whereas the minADC/corpus callosum ratio for DTI and the ratio
of Cho/Cr for MRS of the solid tumoral region provided the best diagnostic
performance (p < 0.05). With a predetermined threshold for each parametric
measurement, the combination of all advanced MRI modalities was associated with
the best accuracy whereas the combination of DSC MRI and MRS provided the highest
specificity. When all parametric measurements were positive, the probability of
HGG was 0.889. CONCLUSION: Comprehensive advanced MRI studies provided better
diagnostic performance than using conventional MRI alone in the evaluation of
gliomas.
PMID- 24350421
TI - The specimen handling of GI mucosal biopsy: a simple and effective quality
improvement initiative.
AB - OBJECTIVE: Histologic diagnostic foci on GI mucosal biopsy may be patchy.
Therefore, slides with good orientation of mucosal tissue in a perpendicular
plane and demonstrating an entire layer of mucosa will increase the diagnostic
yield. Department of Pathology Faculty of Medicine Siriraj Hospital has launched
the two steps quality improvement program and a parallel research aiming to
demonstrate the importance of tissue orientation of GI biopsy. MATERIAL AND
METHOD: Step 1: quality improvement was introduced at the pathology laboratory.
Embedding technicians were trained to embed tissue in perpendicular plane. Step
2: quality improvement at endoscopy unit, endoscopic nurses were trained to
spread the biopsy tissues on a mesh with upward mucosal surface before fixing
them into formalin. Three sets of 50 consecutive cases of GI mucosal biopsy were
retrieved from before, after step 1, and after step 2. The number of high quality
slides, diagnostic discrepancy, and diagnostic confidence of the pathologists
were compared between the three sets. RESULTS: High quality slides were
significantly increased from 23 (46%) before quality improvement to 30 (60%)
after step 1, and 37 (74%) after step 2 (p-value = 0.017). Diagnostic discrepancy
was decreased while diagnostic confidence was increased after quality
improvement. CONCLUSION: The quality of GI mucosal biopsy slides were
significantly improved after a simple and feasible program indicating that both
educating and training of medical personnel for tissue procurement and tissue
processing are crucial. Higher quality of slide can lead to more accurate
diagnosis and fewer laboratory resources used.
PMID- 24350422
TI - Cervical myelopathy from retro-odontoid calcium pyrophosphate dihydrate mass: a
case report.
AB - Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is one of the
most common forms of crystal-associated arthropathy in the elderly. However,
cervical spine is rarely affected, especially in upper cervical area. There have
been previous reported cases of symptomatic retro-odontoid CPPD deposition
disease in English literature but this case is the first reported in Thai
patients. This is a case report of a 67-year-old man who presented with neck pain
with progressive myelopathy. Neurologic examination demonstrated a cervical
myelopathy with muscle weakness and sensory disturbance of both extremities.
Imaging studies showed extradural retro-odontoid mass compressing the spinal
cord. The patient underwent occiput to C3 fusion with plating, posterior arch of
atlas resection, transoral odontoidectomy, and mass removal. Histological
examination of the mass revealed fibrocartilage tissue and rhomboid shaped
crystals that showed positive biferingent in polarized light microscopy
consistent with CPPD crystals. After surgery, no complication was found, and his
neurological function had improved.
PMID- 24350423
TI - Trials registration: a new era in Thailand.
AB - Registration of clinical trials or research can result in many benefits. Patients
have access to pertinent information. We have a better and more indicative
picture of research status in areas where registration is mandatory. Researchers
can use the information to form a common interest group and collaborate their
research as well as to avoid unnecessary duplication. Registered information can
also enable detection of defective design and can lead to improvements of trial
protocol or its implementation. Most importantly, it can help to reduce problems
of publication bias and selective reporting. Journals do not like to publish
negative or inconclusive results. Pharmaceutical companies are reluctant to
report results that may jeopardize their revenue. We need absolute transparency
to utilize evidence with trust.
PMID- 24350424
TI - Special issue: Sustainable technologies: bioenergy and biofuel from biowaste and
biomass.
PMID- 24350425
TI - Bacterial synthesis gas (syngas) fermentation.
AB - Acetogenic bacteria employing the Wood-Ljungdahl pathway can be used as
biocatalysts in syngas fermentation for the production ofbiofuels such as ethanol
or butanol as well as biocommodities such as acetate, lactate, butyrate, 2,3
butanediol, and acetone. The potential of such processes can be projected by the
global syngas output, which was 70,817 megawatts thermal in 2010 and is expected
to increase up to 72% in 2016. To date, different acetogens are used as
commercial production strains for industrial syngas fermentations in pilot or
demonstration plants (Coskata, INEOS Bio, LanzaTech) and first commercial units
are expected to launch operation in the near future (INEOS Bio, LanzaTech).
Considerations on potential yields are quite promising for fermentative
production. New methods for metabolic engineering were established to construct
novel recombinant acetogenic biocatalysts. Synthetic biology will certainly play
a major role in constructing strains for commercial operations. This way, a cheap
and abundant carbon source most probably replace, processes based on crude oil or
sugar in the near future.
PMID- 24350426
TI - Trends in biohydrogen production: major challenges and state-of-the-art
developments.
AB - Hydrogen has shown enormous potential to be an alternative fuel of the future.
Hydrogen production technology has gained much attention in the last few decades
due to advantages such as its high conversion efficiency, recyclability and non
polluting nature. Over the last few decades, biological hydrogen production has
shown great promise for generating large scale sustainable energy to meet ever
increasing global energy demands. Various microorganisms, namely bacteria,
cyanobacteria, and algae which are capable of producing hydrogen from water,
solar energy, and a variety of organic substrates, are explored and studied in
detail. Current biohydrogen production technologies, however, face two major
challenges such as low-yield and high production cost. Advances have been made in
recent years in biohydrogen research to improve the hydrogen yield through
process modifications, physiological manipulations, through metabolic and genetic
engineering. Recently, cell immobilization such as microbes trapping with
nanoparticles within the bioreactor has shown an increase in hydrogen production.
This review critically evaluated various biological hydrogen production
technologies, key challenges, and recent advancements in biohydrogen research and
development.
PMID- 24350427
TI - Household anaerobic digester for bioenergy production in developing countries:
opportunities and challenges.
AB - Access to clean and affordable energy is vital for advancing development
objectives, particularly in rural areas of developing countries. There are some
three billion people in these regions, however, who lack consistent access to
energy and rely on traditional solid fuels such as firewood, cattle manure, and
crop residues for meeting cooking and heating needs. Excessive use of such highly
polluting resources creates serious environmental, social and public health
issues. In this context, household digesters (which convert readily available
feedstocks such as cattle manure, human excreta, and crop residues into biogas)
have the potential to play a significant role in supplying methane as a clean,
renewable energy resource for remote geographies. In addition to bioenergy
production, the slurry generated from anaerobic digestion is rich in nutrients
and can improve the physical, chemical, and biological attributes of soil when
applied to agricultural land. This type of approach has the potential to
significantly reduce greenhouse gas emissions while simultaneously improving the
quality of life. Despite a long history of research and innovation for the
development and optimization of household digesters, little is known and has been
reported for the application of these systems in decentralized communities. The
primary purpose of this paper seeks to review the dearth of literature pertaining
to small-scale anaerobic digesters in remote geographies and in regions where
much of the world's population reside.
PMID- 24350428
TI - Butanol fermentation.
AB - This review provides an overview on bacterial butanol production and recent
developments concerning strain improvement, newly built butanol production
plants, and the importance of alternative substrates, especially lignocellulosic
hydrolysates. The butanol fermentation using solventogenic clostridial strains,
particularly Clostridium acetobutylicum, is a very old industrial process
(acetone-butanol-ethanol-ABE fermentation). The genome of this organism has been
sequenced and analysed, leading to important improvements in rational strain
construction. As the traditional ABE fermentation process is economically
unfavourable, novel butanol production strains are being developed. In this
review, some newly engineered solvent-producing Clostridium strains are described
and strains of which sequences are available are compared with C. acetobutylicum.
Furthermore, the past and present of commercial butanol fermentation are
presented, including active plants and companies. Finally, the use of biomass as
substrate for butanol production is discussed. Some advances concerning
processing of biomass in a biorefinery are highlighted, which would allow
lowering the price of the butanol fermentation process at industrial scale.
PMID- 24350429
TI - Membrane bioreactors' potential for ethanol and biogas production: a review.
AB - Companies developing and producing membranes for different separation purposes,
as well as the market for these, have markedly increased in numbers over the last
decade. Membrane and separation technology might well contribute to making fuel
ethanol and biogas production from lignocellulosic materials more economically
viable and productive. Combining biological processes with membrane separation
techniques in a membrane bioreactor (MBR) increases cell concentrations
extensively in the bioreactor. Such a combination furthermore reduces product
inhibition during the biological process, increases product concentration and
productivity, and simplifies the separation of product and/or cells. Various MBRs
have been studied over the years, where the membrane is either submerged inside
the liquid to be filtered, or placed in an external loop outside the bioreactor.
All configurations have advantages and drawbacks, as reviewed in this paper. The
current review presents an account of the membrane separation technologies, and
the research performed on MBRs, focusing on ethanol and biogas production. The
advantages and potentials of the technology are elucidated.
PMID- 24350430
TI - Sustainability of soil fertility and the use of lignocellulosic crop harvest
residues for the production of biofuels: a literature review.
AB - Use of lignocellulosic crop harvest residues for liquid or gaseous biofuel
production may impact soil quality, long-term soil fertility and the major
determinants of the latter, stocks of soil organic carbon and nutrients. When
soil organic carbon stocks of mineral cropland soils are to be maintained, there
is scope for the removal of lignocellulosic harvest residues in several systems
with much reduced tillage or no tillage. The scope for such removal might be
increased when suitably treated residues from the conversion of harvest residues
into biofuel are returned to cropland soils. For mineral cropland soils under
conventional tillage, the scope for the production of liquid biofuels from
harvest residues is likely to be less than in the case of no-till systems. When
fertility of cropland soils is to be sustainable, nutrients present in suitably
treated biofuel production residues have to be returned to these soils.
Apparently, the actual return of carbon and nutrients present in residues of
biofuel production from crop harvest residues to arable soils currently
predominantly concerns the application of digestates of anaerobic digestion. The
effects thereof on soil fertility and quality need further clarification. Further
clarification about the effects on soil fertility and quality of chars and of co
products of lignocellulosic ethanol production is also needed.
PMID- 24350431
TI - Supercritical CO2 and ionic liquids for the pretreatment of lignocellulosic
biomass in bioethanol production.
AB - Owing to high petroleum prices, there has been a major push in recent years to
use lignocellulosic biomass as biorefinery feedstocks. Unfortunately, by nature's
design, lignocellulosic biomass is notoriously recalcitrant. Cellulose is the
most abundant renewable carbon source on the planet and comprises glucan
polysaccharides which self-assemble into paracrystalline microfibrils. The extent
of cellulose crystallinity largely contributes to biomass recalcitrance.
Additionally, cellulose microfibrils are embedded into both hemicellulose and
lignin polymeric networks, making cellulose accessibility an additional obstacle.
Pretreatment is necessary before enzymatic hydrolysis in order to liberate high
yields of glucose and other fermentable sugars from biomass polysaccharides. This
work discusses two pretreatment methods, supercritical CO2 and ionic liquids
(ILs). Both methods utilize green solvents that do not emit toxic vapours.
Mechanisms for destroying or weakening biomass recalcitrance have been explored.
Various pretreatment operating parameters such as temperature, pressure, time,
dry biomass/solvent ratio, water content, etc. have been investigated for the
pretreatment of various biomass types such as corn stover, switchgrass, sugarcane
bagasse, soft and hard wood. The two pretreatment methods have their pros and
cons. For example, supercritical CO2 explosion pretreatment uses inexpensive CO2,
but requires a high pressure. By comparison, while IL pretreatment does not
require an elevated pressure, ILs are still too expensive for large-scale uses.
Further research and development are needed to make the two green pretreatment
methods practical.
PMID- 24350432
TI - Membranes for bioelectrochemical systems: challenges and research advances.
AB - Increasing energy demand has been a big challenge for current society, as the
fossil fuel sources are gradually decreasing. Hence, development of renewable and
sustainable energy sources for the future is considered one of the top priorities
in national strategic plans. Bioenergy can meet future energy requirements -
renewability, sustainability, and even carbon-neutrality. Bioenergy production
from wastes and wastewaters is especially attractive because of dual benefits of
energy generation and contaminant stabilization. There are several bioenergy
technologies using wastes and wastewaters as electron donor, which include
anaerobic digestion, dark biohydrogen fermentation, biohydrogen production using
photosynthetic microorganisms, and bioelectrochemical systems (BESs). Among them
BES seems to be very promising as we can produce a variety of value-added
products from wastes and wastewaters, such as electric power, hydrogen gas,
hydrogen peroxide, acetate, ethanol etc. Most ofthe traditional BES uses a
membrane to separate the anode and cathode chamber, which is essential for
improving microbial metabolism on the anode and the recovery of value-added
products on the cathode. Performance of BES lacking a membrane can be seriously
deteriorated, due to oxygen diffusion or substantial loss of synthesized
products. For this reason, usage of a membrane seems essential to facilitate BES
performance. However, a membrane can bring several technical challenges to BES
application compared to membrane-less BES. These challenges include poor proton
permeability, substrate loss, oxygen back diffusion, pH gradient, internal
resistance, biofouling, etc. This paper aims to review the major technical
barriers associated with membranes and future research directions for their
application in BESs.
PMID- 24350433
TI - Improving the feasibility of producing biofuels from microalgae using wastewater.
AB - Biofuels have received much attention recently owing to energy consumption and
environmental concerns. Despite many of the technologies being technically
feasible, the processes are often too costly to be commercially viable. The major
stumbling block to full-scale production of algal biofuels is the cost of
upstream and downstream processes and environmental impacts such as water
footprint and indirect greenhouse gas emissions from chemical nutrient
production. The technoeconomics of biofuels production from microalgae is
currently unfeasible due to the cost of inputs and productivities achieved. The
use of a biorefinery approach sees the production costs reduced greatly due to
utilization of waste streams for cultivation and the generation of several
potential energy sources and value-added products while offering environmental
protection. The use of wastewater as a production media, coupled with CO2
sequestration from flue gas greatly reduces the microalgal cultivation costs.
Conversion of residual biomass and by-products, such as glycerol, for fuel
production using an integrated approach potentially holds the key to near future
commercial implementation of biofuels production.
PMID- 24350434
TI - An assessment of the economic aspects of CO2 sequestration in a route for
biodiesel production from microalgae.
AB - Photosynthetic microalgae are unicellular organisms that, during their
cultivation, can fix carbon dioxide efficiently from various sources, including
the air and exhaust gases from industrial processes. This feature can lead to
economic benefits in the production process of biodiesel by way of the clean
development mechanism, for which carbon credits for environmental benefits may be
granted and which will contribute towards reducing costs in the production
process. This study seeks to quantify the contribution of carbon credits in the
operating costs of a route for biodiesel production from microalgae, as proposed
by Davis et al. [Techno-economic analysis ofautotrophic microalgae for fuel
production. Appl Energy. 2011; 88:3524-3531]. The results showed a reduction in
annual operating costs by around 5%. This figure may be conservative, since the
production process considered can be further improved to reduce operating costs
and thus increase the contribution margin of carbon credits, which will reduce
costs. On the other hand, the price of carbon may also rise in the future,
thereby increasing its contribution towards a reduction in operating costs.
PMID- 24350435
TI - Addressing the challenges for sustainable production of algal biofuels: I. Algal
strains and nutrient supply.
AB - Microalgae hold promise for the production of sustainable replacement of fossil
fuels due to their high growth rates, ability to grow on non-arable land and
their high content, under the proper conditions, of high energy compounds that
can be relatively easily chemically converted to fuels using existing technology.
However, projected large-scale algal production raises a number of sustainability
concerns concerning land use, net energy return, water use and nutrient supply.
The state-of-the-art of algal production of biofuels is presented with emphasis
on some possible avenues to provide answers to the sustainability questions that
have been raised. Here, issues concerning algal strains and supply of nutrients
for large-scale production are discussed. Since sustainability concerns
necessitate the use of wastewaters for supply of bulk nutrients, emphasis is
placed on the composition and suitability of different wastewater streams. At the
same time, algal cultivation has proven useful in waste treatment processes, and
thus this aspect is also treated in some detail.
PMID- 24350437
TI - Conversion of switchgrass to ethanol using dilute ammonium hydroxide
pretreatment: influence of ecotype and harvest maturity.
AB - Switchgrass (Panicum virgatum L.) is a perennial C4 grass that is being developed
as a bioenergy crop because it has high production yields and suitable agronomic
traits. Five switchgrass biomass samples from upland and lowland switchgrass
ecotypes harvested at different stages or maturity were used in this study.
Switchgrass samples contained 317.0-385.0 g glucans/kg switchgrass dry basis (db)
and 579.3-660.2 g total structural carbohydrates/kg switchgrass, db. Carbohydrate
contents were greater for the upland ecotype versus lowland ecotype and increased
with harvest maturity. Pretreatment of switchgrass with dilute ammonium hydroxide
(8% w/w ammonium loading) at 170 degrees C for 20 min was determined to be
effective for preparing switchgrass for enzymatic conversion to monosaccharides;
glucose recoveries were 66.9-90.5% and xylose recoveries 60.1-84.2% of maximum
and decreased with increased maturity at harvest. Subsequently, pretreated
switchgrass samples were converted to ethanol by simultaneous saccharification
and fermentation using engineered xylose-fermenting Saccharomyces cerevisiae
strain YRH400. Ethanol yields were 176.2-202.01/Mg of switchgrass (db) and
followed a similar trend as observed for enzymatic sugar yields.
PMID- 24350436
TI - Addressing the challenges for sustainable production of algal biofuels: II.
Harvesting and conversion to biofuels.
AB - In order to ensure the sustainability of algal biofuel production, a number of
issues need to be addressed. Previously, we reviewed some of the questions in
this area involving algal species and the important challenges of nutrient supply
and how these might be met. Here, we take up issues involving harvesting and the
conversion ofbiomass to biofuels. Advances in both these areas are required if
these third-generation fuels are to have a sufficiently high net energy ratio and
a sustainable footprint. A variety of harvesting technologies are under
investigation and recent studies in this area are presented and discussed. A
number of different energy uses are available for algal biomass, each with their
own advantages as well as challenges in terms of efficiencies and yields. Recent
advances in these areas are presented and some of the especially promising
conversion processes are highlighted.
PMID- 24350438
TI - Landfill leachate--a water and nutrient resource for algae-based biofuels.
AB - There is a pressing need for sustainable renewable fuels that do not negatively
impact food and water resources. Algae have great potential for the production of
renewable biofuels but require significant water and fertilizer resources for
large-scale production. Municipal solid waste (MSW) landfill leachate (LL) was
evaluated as a cultivation medium to reduce both water and elemental fertilizer
demands of algae cultivation. Daily growth rate and cell yield of two isolated
species of algae (Scenedesmus cf. rubescens and Chlorella cf. ellipsoidea) were
cultivated in MSW LL and compared with Bold's Basal Medium (BBM). Results suggest
that LL can be used as a nutrient resource and medium for the cultivation of
algae biomass. S. cf. rubescens grew well in 100% LL, when pH was regulated, with
a mean growth rate and cell yield 91.2% and 92.8% of those observed in BBM,
respectively. S. cf. rubescens was more adaptable than C. cf. ellipsoidea to the
LL tested. The LL used in this study supported a maximum volumetric productivity
of 0.55 g/L/day of S. cf. rubescens biomass. The leachate had sufficient nitrogen
to supply 17.8 g/L of algae biomass, but was limited by total phosphorus.
Cultivation of algae on LL offsets both water and fertilizer consumption,
reducing the environmental footprint and increasing the potential sustainability
of algae-based biofuels.
PMID- 24350439
TI - The analysis of macroalgae biomass found around Hawaii for bioethanol production.
AB - Macroalgae commonly found in the ocean around Hawaii were collected from near
shore locations and their potential as biomass feedstock for fermentative ethanol
was investigated. A green alga, Ulva reticulata, was selected for further
analysis. This species forms large complex structures that grow quickly and has
high dry biomass percentage (20%), soluble carbohydrates (18%); and high total
carbohydrates along with low quantities of lignin (13%). During acid
saccharification, it was determined that 49% of the total mass was observed as
sugars in the hydrolysate; however, fermentation was problematic. Enzymatic
saccharification using cellulase from Trichoderma reesei was attempted which
recovered a measured maximum of 20% glucose based on the initial dry mass.
Fermentation successfully converted all the glucose to ethanol. The measured
ethanol yield corresponded to approximately 90 L per tonne of dried macroalgae.
PMID- 24350440
TI - Photosynthesis-fermentation hybrid system to produce lipid feedstock for algal
biofuel.
AB - To avoid bacterial contamination due to medium replacement in the expanded
application of a photosynthesis-fermentation model, an integrated photosynthesis
fermentation hybrid system was set up and evaluated for algal lipid production
using Chlorella protothecoides. In this system, the CO2-rich off-gas from the
fermentation process was recycled to agitate medium in thephotobioreactor, which
could provide initial cells for the heterotrophic fermentation. The cell
concentration reached 1.03 +/- 0.07 g/L during photoautotrophic growth and then
the concentrated green cells were switched to heterotrophic fermentation after
removing over 99.5% ofnitrogen in the medium by a nitrogen removal device. At the
end offermentation in the system, the cell concentration could reach as high as
100.51 +/- 2.03 g/L, and 60.05 +/- 1.38% lipid content was achieved
simultaneously. The lipid yield (60.36 +/- 2.63 g/L) in the hybrid system was
over 700 times higher than that in a photobioreactor and exceeded that by
fermentation alone (47.56 +/- 7.31 g/L). The developed photosynthesis
fermentation hybrid system in this study was not only a feasible option to
enhance microalgal lipid production, but also an environment-friendly approach to
produce biofuel feedstock through concurrent utilization of ammonia nitrogen,
CO2, and organic carbons.
PMID- 24350441
TI - Algal biomass production and wastewater treatment in high rate algal ponds
receiving disinfected effluent.
AB - Algal biomass production associated with wastewater is usually carried out in
high rate algal ponds (HRAPs), which are concomitantly used in the treatment of
such effluent. However, most types of wastewater have high levels of bacteria
that can inhibit the growth of algal biomass by competing for space and
nutrients. The objective of this study was to assess the influence of ultraviolet
(UV) pre-disinfection on the performance of HRAPs used for wastewater treatment
and algal biomass production. Two HRAPs were tested: one received effluent from
an upflow anaerobic sludge blanket (UASB) reactor- HRAP -and the second received
UASB effluent pre-disinfected by UV radiation-(UV)HRAP. Physical, chemical and
microbiological parameters were monitored, as well as algal biomass productivity
and daily pH and dissolved oxygen (DO) variation. The (UV)HRAP presented highest
DO and pH values, as well as greater percentage of chlorophyll a in the biomass,
which indicates greater algal biomass productivity. The average percentages of
chlorophyll a found in the biomass obtained from the HRAP and the (UV)HRAP were
0.95 +/- 0.65% and 1.58 +/- 0.65%, respectively. However, total biomass
productivity was greater in the HRAP (11.4 gVSSm(-2) day(-1)) compared with the
(UV)HRAP (9.3 gVSSm(-2) day(-1)). Mean pH values were 7.7 +/- 0.7 in the HRAP and
8.1 +/- 1.0 in the (UV)HRAP, and mean values of DO percent saturation were 87 +/-
26% and 112 +/- 31% for the HRAP and the (UV)HRAP, respectively. Despite these
differences, removal efficiencies of organic carbon, chemical oxygen demand,
ammoniacal nitrogen and soluble phosphorus were statistically equal at the 5%
significance level.
PMID- 24350442
TI - Effects of calcium, magnesium and sodium chloride in enhancing lipid accumulation
in two green microalgae.
AB - Biodiesel from microalgae has the potential as a sustainable fuel, since some
species show exceptionally high lipid accumulation potential under various
stresses. Effects of different concentrations of Ca, Mg and NaCl in the growth
medium on biomass yield and lipid accumulation of Chlorella vulgaris and
Scenedesmus obliquus grown under batch culture mode were investigated. Starvation
of Mg showed a marginal rise in lipid content for a short period of time. Ca
starved cultures, however, demonstrated a profound rise in lipid content, i.e.
40% of dry cell wt. (dcw) was recorded against 11.9% control for C. vulgaris and
37% (dcw) against 11.3% for S. obliquus. Under increased concentration of Mg,
significant rise in biomass and lipid yield was recorded. Effect of NaCl-induced
osmotic stress showed lipid accumulation of approximately 40% (dcw) in both the
test algae, whereas the biomass yield was severely affected. The fatty acid
profiles under the above stresses were analysed and discussed.
PMID- 24350443
TI - Screening for novel bacteria from the bioenergy feedstock switchgrass (Panicum
virgatum L.).
AB - Switchgrass is considered as a good candidate for biofuel, especially ethanol
production due to its huge biomass output and high cellulose content. In a search
for novel microorganisms capable of using and degrading switchgrass to produce
sugars and ethanol, enrichment experiments were established to screen for
microorganisms from soil samples obtained at the University of Tennessee
Agricultural Research Station, Jackson, Tennessee. Three enrichments were
prepared and incubated at different pH and temperatures: (1) 30 degrees C, pH 5,
(2) 30 degrees C, pH 8 and (3) 60 degrees C, pH5. Bulk community DNA was directly
extracted from the enrichments. Microbial community structures were determined by
phylogenetic analysis of 16S rRNA gene sequences retrieved from the enrichment
cultures containing switchgrass as the carbon source. The mesophilic enrichments
were dominated by Sarcina, Anaerobacter, and Clostrium, which were not found in
the thermophilic enrichment. The thermophilic enrichment selected for two types
of bacteria belonging to the class Bacilli (Geobacillus and Saccharococcus). The
thermophilic enrichments were dominated by the Geobacillus spp. (Firmicutes,
class Bacilli), and Saccharococcus (Firmicutes, class Bacilli); both containing
thermophilic microorganisms with some cellulolytic members. Enzymatic assays
detected the presence of enzymes involved in cellulose (beta-glucosidase and
cellobiohydrolase) and hemicellulose degradations (beta-xylosidase); and the
activity tends to be higher in the enrichments incubated at 30 degrees C.
PMID- 24350444
TI - A cooperative microbial fuel cell system for waste treatment and energy recovery.
AB - A cooperative microbial fuel cell (MFC) system was developed and investigated for
its performance in waste treatment and bioenergy production. The system consisted
of a conventional MFC and a dual-cathode MFC that was specially designed for
nitrogen removal. Three feeding solutions, including a synthetic solution
(acetate as an organic source), digested sludge and landfill leachate, were used
as substrates. The MFC system removed more than 99% of chemical oxygen demand
(COD) from the synthetic solution, and the organic removal mainly occurred in the
anodes of the MFCs. Nitrogen, on the other hand, was removed in the cathodes of
the MFC system, which achieved more than 98% removal of ammonium and 96% removal
of total nitrogen. The MFC system also effectively treated the actual wastes and
removed more than 85% of the total COD and 50-70% of the total nitrogen from the
digested sludge and landfill leachate. The organic removal rates with the actual
wastes were significantly higher than in other MFC systems. In general, the MFC
system consumed less than 0.06 kWh/m3 or 0.1 kWh/kg COD, demonstrating that low
energy consumption is a major advantage of MFC technology. The MFC system
produced 0.1023 kWh/kg COD from the synthetic solution, much higher than the
0.0097 kWh/kg COD and 0.0019 kWh/kg COD from the actual wastes, resulting in a
theoretically positive energy balance with the synthetic solution; however, the
net energy with the actual wastes was negative.
PMID- 24350445
TI - Microbial fuel cells and microbial electrolysis cells for the production of
bioelectricity and biomaterials.
AB - Today's global energy crisis requires a multifaceted solution. Bioenergy is an
important part of the solution. The microbial fuel cell (MFC) technology stands
out as an attractive potential technology in bioenergy. MFCs can convert energy
stored in organic matter directly into bioelectricity. MFCs can also be operated
in the electrolysis mode as microbial electrolysis cells to produce bioproducts
such as hydrogen and ethanol. Various wastewaters containing low-grade organic
carbons that are otherwise unutilized can be used as feed streams for MFCs.
Despite major advances in the past decade, further improvements in MFC power
output and cost reduction are needed for MFCs to be practical. This paper
analysed MFC operating principles using bioenergetics and bioelectrochemistry.
Several major issues were explored to improve the MFC performance. An emphasis
was placed on the use of catalytic materials for MFC electrodes. Recent advances
in the production of various biomaterials using MFCs were also investigated.
PMID- 24350446
TI - Effect of temperature change on power generation of microbial fuel cell.
AB - Microbial fuel cell (MFC), which can directly generate electricity from
biodegradable materials, has been receiving increasing attention. Effects of
temperature change on power density, electrode potential, columbic efficiency,
chemical oxygen demand removal and internal resistance in two chambers MFCs were
examined in this paper. The maximum power density of 7.89 W/m3 was achieved at 37
degrees C, with 199% higher at 10 degrees C (2.64 W/m3), 24% higher at 30 degrees
C (6.34 W/m3) and 21% higher at 43 degrees C, no steady power generation was
observed at 55 degrees C. Low temperature to 10 degrees C might have a huge
effect on anode potential, especially at higher current, but increasing the
temperature to 43 degrees C had a main effect on the cathode performance when the
MFCs have been established at 37 degrees C. The internal resistance of MFC was
about 29 omega at 37 degrees C, and increased 62% and 303% when MFC switched to
30 degrees C and 10 degrees C. Similarly, internal resistance increased 48% at 43
degrees C. The effect of temperature on MFC performance was expressed by internal
resistance, the higher the internal resistance of MFC, the lesser the power
density obtained. The Columbic efficiencies were 8.65% at 30 degrees C, 8.53% at
37 degrees C, and 13.24% at 43 degrees C. These results demonstrate that MFCs can
effectively be operated over a wide range of temperatures.
PMID- 24350447
TI - Integrated conversion of food waste diluted with sewage into volatile fatty acids
through fermentation and electricity through a fuel cell.
AB - In this study, domestic wastewater was given a second life as dilution medium for
concentrated organic waste streams, in particular artificial food waste. A two
step continuous process with first volatile fatty acid (VFA)/hydrogen production
and second electricity production in microbial fuel cells (MFCs) was employed.
For primary treatment, bioreactors were optimized to produce hydrogen and VFAs.
Hydrolysis of the solids and formation of fermentation products and hydrogen was
monitored. In the second step, MFCs were operated batch-wise using the effluent
rich in VFAs specifically acetic acid from the continuous reactor of the first
step. The combined system was able to reduce the chemical oxygen demand load by
90%. The concentration of VFAs was also monitored regularly in the MFCs and
showed a decreasing trend over time. Further, the anode potential changed from
500 to OmV vs. Ag/AgCl when the VFAs (especially acetate) were depleted in the
system. On feeding the system again with the effluent, the anode potential
recovered back to -500 mV vs. Ag/AgCl. Thus, the overall aim of converting
chemical energy into electrical energy was achieved with a columbic efficiency of
46% generating 65.33 mA/m2 at a specific cell potential of 148 mV.
PMID- 24350448
TI - A flat microbial fuel cell for decentralized wastewater valorization: process
performance and optimization potential.
AB - A very compact flat microbial fuel cell (MFC), with 64 cm2 each for the anode
surface and the cathode surface and 1 cm3 each for the anode and cathode
chambers, was tested for wastewater treatment with simultaneous electricity
production with the ultimate goal of implementing an autonomous service in
decentralized wastewater treatment systems. The MFC was operated with municipal
wastewater in sequencing batch reactor mode with re-circulation. Current
densities up to 407 W/m3 and a carbon removal of 83% were obtained. Interruption
in the operation slightly decreased power density, while the re-circulation ratio
did not influence power generation. The anode biofilm presented high
conductivity, activity and diversity. The denaturing gradient gel electrophoresis
band-pattern of the DNA showed the presence of several ribotypes with different
species of Shewanellaceae and Geobacteraceae families.
PMID- 24350449
TI - Inoculum selection to enhance performance of a microbial fuel cell for
electricity generation during wastewater treatment.
AB - Experiments were designed to evaluate the influence of various anaerobic
inoculums to enhance microbial fuel cell (MFC) performance utilizing tannery
wastewater as substrate. Three bacterial electrogenic strains, tolerant to
tannery environment, were isolated from soil contaminated with tannery waste and
tannery wastewater was inoculated with these monotypes and mixed consortia of
three bacterial strains in different MFCs. Comparative analysis was made by
treating the tannery wastewater with foreign microbial consortia (activated
sludge inoculum) and with only natural habitat microbes already present in plain
wastewater. It was observed that inoculum contributes great effect on the MFC
performance. Among the studied inoculation strategies, mixed electrogenic strain
inocula enabled higher current yield along with concurrent substrate removal
efficiency. On the contrary, plain wastewater resulted in relatively low
efficiency.
PMID- 24350450
TI - Effect of thermal pre-treatment on inoculum sludge to enhance bio-hydrogen
production from alkali hydrolysed rice straw in a mesophilic anaerobic baffled
reactor.
AB - The effect of thermal pre-treatment on inoculum sludge for continuous H2
production from alkali hydrolysed rice straw using anaerobic baffled reactor
(ABR) was investigated. Two reactors, ABR1 and ABR2, were inoculated with
untreated and thermally pre-treated sludge, respectively. Both reactors were
operated in parallel at a constant hydraulic retention time of 20 h and organic
loading rate ranged from 0.5 to 2.16 g COD/L d. The results obtained indicated
that ABR2 achieved a better hydrogen conversion rate and hydrogen yield as
compared with ABR1. The hydrogen conversion rates were 30% and 24%, while the
hydrogen yields were 1.19 and 0.97 mol H2/mol glucose for ABR2 and ABR1,
respectively. Similar trend was observed for chemical oxygen demand (COD) and
carbohydrate removal, where ABR2 provided a removal efficiency of 53 +/- 2.3% for
COD and 46 +/- 2% for carbohydrate. The microbial community analysis using 16S
rRNA phylogeny revealed the presence of different species of bacteria, namely
Clostridium, Prevotella, Paludibacter, Ensifer, and Petrimonas within the
reactors. Volatile fatty acids generated from ABR1 and ABR2 were mainly in the
form of acetate and butyrate and a relatively low fraction ofpropionate was
detected in ABR1. Based on these results, thermal pre-treatment ofinoculum sludge
is preferable for hydrogen production from hydrolysed rice straw.
PMID- 24350451
TI - Crustacean zooplankton in aerated wastewater treatment lagoons as a potential
feedstock for biofuel.
AB - Zooplankton biomass productivity was estimated for two 64,000 m3 (1.7 ha)
facultative aerated wastewater treatment lagoons to evaluate potential biodiesel
production from zooplankton biomass. Lagoons were monitored bi-weekly during
summer 2010. Lipid accumulated by crustacean zooplankton was considered the most
efficient means by which to collect lipid produced by phytoplankton owing to the
greater ease in the collection of these organisms (>0.153mm) compared with
unicellular algae (size <0.06 mm). In terms of biomass, the cladoceran Daphnia
and the copepod Cyclops were the dominant zooplankton in these hypereutrophic
lagoons, while unicellular chlorophytes dominated the phytoplankton community.
Secondary productivity of these lagoons (250 g of dry weight m(-2) yr(-1)) is
comparable to the secondary productivity of other sewage lagoons. The potential
biodiesel production for one lagoon was estimated to be 0.04 +/- 0.02 L m(-2) yr(
1), which results in a total of 1120 +/- 560 L from two lagoons. This study
showed that there are organisms present in wastewater lagoons, besides algae,
that can serve as a biofuel feedstock. Additionally, this research expands the
current knowledge of facultative aerated wastewater lagoon ecology and waste
stream-derived biofuel. Future research should include complete life cycle and
economic analyses to determine if harvesting zooplankton from wastewater lagoons
is a sustainable endeavour.
PMID- 24350452
TI - Integrating syngas fermentation with the carboxylate platform and yeast
fermentation to reduce medium cost and improve biofuel productivity.
AB - To ensure economic implementation of syngas fermentation as a fuel-producing
platform, engineers and scientists must both lower operating costs and increase
product value. A considerable part of the operating costs is spent to procure
chemicals for fermentation medium that can sustain sufficient growth of
carboxydotrophic bacteria to convert synthesis gas (syngas: carbon monoxide,
hydrogen, and carbon dioxide) into products such as ethanol. Recently, we have
observed that wildtype carboxydotrophic bacteria (including Clostridium
ljungdahlii) can produce alcohols with a longer carbon chain than ethanol via
syngas fermentation when supplied with the corresponding carboxylic acid
precursors, resulting in possibilities of increasing product value. Here, we
evaluated a proof-of-concept system to couple syngas fermentation with the
carboxylate platform to both lower medium costs and increase product value. Our
carboxylate platform concept consists of an open culture, anaerobic fermentor
that is fed with corn beer from conventional yeast fermentation in the corn
kernel-to-ethanol industry. The mixed-culture anaerobic fermentor produces a
mixture ofcarboxylic acids at dilute concentrations within the carboxylate
platform effluent (CPE). Besides providing carboxylic acid precursors, this
effluent may represent an inexpensive growth medium. An elemental analysis
demonstrated that the CPE lacked certain essential trace metals, but contained
ammonium, phosphate, sodium, chloride, potassium, magnesium, calcium, and
sulphate at required concentrations. CPE medium with the addition of a trace
metal solution supported growth and alcohol production of C. ljungdahlii at
similar or better levels compared with an optimized synthetic medium (modified
ATCC 1754 medium). Other expensive supplements, such as yeast extract or macro
minerals (ammonium, phosphate), were not required. Finally, n-butyric acid and n
caproic acid within the CPE were converted into their corresponding medium-chain
alcohols n-butanol and n-hexanol.
PMID- 24350453
TI - Isolation and screening of carboxydotrophs isolated from composts and their
potential for butanol synthesis.
AB - Carboxydotrophs are known for their ability to convert carbon monoxide (CO) to
butanol through fermentation. Such a platform offers a promising alternative
approach to biofuel production from synthesis gas feedstocks. In this study,
carboxydotrophs were isolated from various manure compost. Out of 500 isolates,
only 11 carboxydotrophs (7 mesophiles and 4 thermophiles) were found to utilize
CO as the sole source of carbon and energy. To assess the biochemical basis for
their ability to produce biofuel (butanol), the level of activities of CO
dehydrogenase (CODH), hydrogenase and butanol dehydrogenase (BDH) enzymes for
these isolates against the known carboxydotroph, Butyribacterium methylotrophicum
was assessed. All isolates showed evidence of enzyme activities (0.16-2.20
micromol min(-1)), with the majority exhibiting higher activities compared with
the known carboxydotroph, B. methylotrophicum (0.33-0.71 micromol min(-1)). The
level of activities for CODH and BDH ranged from 0.163-3.59 micromolmin(-1) and
0.19-2.2 micromolmin(-1), respectively. Three isolates (M7-1, T2-22, and T3-14)
demonstrated enzymatic activity three to seven times higher than B.
methylotrophicum. Of these, T2-22 exhibited the highest BDH activity and shows
great promise in the conversion of toxic CO into butanol more so than other
carboxytotrophs known thus far. This study revealed some biochemical basis for
butanol production from CO by carboxydotrophs. However, more research is needed
to discover a direct biological route for butanol production from CO to
strengthen their potential for synthesis gas bioprocessing. Follow-up work will
focus on whole-genome sequencing of the promising isolate T2-22 to provide system
level insights into how carboxydotrophs utilize and regulate their molecular
machineries for butanol production.
PMID- 24350454
TI - Comparative assessment of various lipid extraction protocols and optimization of
transesterification process for microalgal biodiesel production.
AB - Biodiesel, using microalgae as feedstocks, is being explored as the most potent
form of alternative diesel fuel for sustainable economic development. A
comparative assessment of various protocols for microalgal lipid extraction was
carried out using five green algae, six blue-green algae and two diatom species
treated with different single and binary solvents both at room temperature and
using a soxhlet. Lipid recovery was maximum with chloroform-methanol in the
soxhlet extractor. Pretreatments ofbiomass, such as sonication, homogenization,
bead-beating, lyophilization, autoclaving, microwave treatment and osmotic shock
did not register any significant rise in lipid recovery. As lipid recovery using
chloroform-methanol at room temperature demonstrated a marginally lower value
than that obtained under the soxhlet extractor, on economical point of view, the
former is recommended for microalgal total lipid extraction. Transesterification
process enhances the quality of biodiesel. Experiments were designed to determine
the effects of catalyst type and quantity, methanol to oil ratio, reaction
temperature and time on the transesterification process using response surface
methodology. Fatty acid methyl ester yield reached up to 91% with
methanol:HCl:oil molar ratio of 82:4:1 at 65 degrees C for 6.4h reaction time.
The biodiesel yield relative to the weight of the oil was found to be 69%.
PMID- 24350455
TI - Experimental investigation on performance and exhaust emissions of castor oil
biodiesel from a diesel engine.
AB - Biodiesel, produced from plant and animal oils, is an important alternative to
fossil fuels because, apart from dwindling supply, the latter are a major source
of air pollution. In this investigation, effects of castor oil biodiesel blends
have been examined on diesel engine performance and emissions. After producing
castor methyl ester by the transesterification method and measuring its
characteristics, the experiments were performed on a four cylinder, turbocharged,
direct injection, diesel engine. Engine performance (power, torque, brake
specific fuel consumption and thermal efficiency) and exhaust emissions were
analysed at various engine speeds. All the tests were done under 75% full load.
Furthermore, the volumetric blending ratios of biodiesel with conventional diesel
fuel were set at 5, 10, 15, 20 and 30%. The results indicate that lower blends of
biodiesel provide acceptable engine performance and even improve it. Meanwhile,
exhaust emissions are much decreased. Finally, a 15% blend of castor oil
biodiesel was picked as the optimized blend of biodiesel-diesel. It was found
that lower blends of castor biodiesel are an acceptable fuel alternative for the
engine.
PMID- 24350456
TI - Evaluation of the biomethane potential from multiple waste streams for a proposed
community scale anaerobic digester.
AB - This paper examines the biomethane potential from organic waste for a proposed
community scale anaerobic digester in a rural town. The biomethane potential test
is used to assess the suitability of waste streams for biomethane production and
to examine the variation in biomethane potential between waste sub-streams. A
methodology for accurately estimating the biomethane potential from multiple
heterogeneous organic waste substrates is sought. Five main waste streams were
identified as possible substrates for biogas production, namely Abattoir waste
(consisting of paunch and de-watered activated sludge); cheese factory effluent;
commercial and domestic food waste; pig slurry and waste water treatment sludge.
The biomethane potential of these waste streams ranged from as low as 99 L CH4 kg
VS(-1) for pig slurry to as high as 787 L CH4 kg VS(-1) for dissolved air
floatation (DAF) sludge from a cheese effluent treatment plant. The kinetic
behaviour of the biomethane production in the batch test is also examined. The
objective of the paper is to suggest an optimum substrate mix in terms of
biomethane yield per unit substrate for the proposed anaerobic digester. This
should maximize the yield of biomethane per capital investment. Food waste
displayed the highest biomethane yield (128 m(n)(3) t(-1)) followed by cheese
waste (38 m(n)(3) t(-1)) and abattoir waste (36 m(n)(3) t(-1)). It was suggested
that waste water sludge (16 m(n)(3) t(-1)) and pig slurry (4 m(n)(3) t(-1))
should not be digested. However, the biomethane potential test does not give
information on the continuous operation of an anaerobic digester.
PMID- 24350457
TI - Selection of microalgae suitable for culturing with digestate from methane
fermentation.
AB - The effects ofdigestate on the growth rates of Euglena gracilis, Chlorella
vulgaris, and Dunaliella tertiolecta were investigated to select suitable
microalgae for culturing with digestate from methane fermentation. Microalgae
were cultured in an aqueous solution containing digestate at concentrations of
5%, 10%, 13%, 20%, 40%, 50%, and 100%, and Cramer-Myers (CM) solution as a
control, at photosynthetic photon flux densities (PPFDs) of 75-150 micromol m(-2)
s(-1) with continuous illumination at 30 degrees C. The number of cells was
monitored daily, and specific growth rates (mu) were calculated as cellular
multiplication rates. The maximum mu values of these species were greater in
appropriate concentrations of digestate than in CM medium. The maximum mu values
were 0.047 h(-1) in 10% digestate for E. gracilis, 0.065 h(-1) in 20% digestate
for C. vulgaris, and 0.052 h(-1) in 50% digestate for D. tertiolecta at a PPFD of
150 micromol m(-2) s(-1). The mu of D. tertiolecta were 2.5 and 1.1 times higher
than those of E. gracilis and C. vulgaris, respectively, in 50% digestate. These
results demonstrated that these species could be cultured at high growth rates
with diluted methane fermentation sludge and that, among these species,
Dunaliella sp. was suitable for culturing at higher concentration of digestate
under relatively low-level light conditions.
PMID- 24350458
TI - Modified batch anaerobic digestion assay for testing efficiencies of trace metal
additives to enhance methane production of energy crops.
AB - Batch biochemical methane potential (BMP) assays to evaluate the methane yield of
biogas substrates such as energy crops are usually carried out with undiluted
inoculum. A BMP assay was performed on two energy crops (green cuttings and grass
silage). Anaerobic digestion was performed both with and without supplementation
of three commercial additives containing trace metals in liquid, solid or
adsorbed form (on clay particles). In order to reveal positive effects of trace
metal supplementation on the methane yield, besides undiluted inoculum, 3-fold
and 10-fold dilutions of the inoculum were applied for substrate digestion.
Diluted inoculum variants were supplemented with both mineral nutrients and pH
buffering substances to prevent a collapse of the digestion process. As expected,
commercial additives had no effect on the digestion process performed with
undiluted inoculum, while significant increases of methane production through
trace element supplementation could be observed on the diluted variants. The
effect of inoculum dilution may be twofold: (1) decrease in trace metal
supplementation from the inoculum and (2) reduction in the initial number of
bacterial cells. Bacteria require higher growth rates for substrate degradation
and hence have higher trace element consumption. According to common knowledge of
the biogas process, periods with volatile fatty acids accumulation and decreased
pH may have occurred in the course ofanaerobic digestion. These effects may have
led to inhibition, not only ofmethanogenes and acetogenes involved in the final
phases of methane production, but also offibre-degrading bacterial strains
involved in polymer hydrolysis. Further research is required to confirm this
hypothesis.
PMID- 24350459
TI - Evaluation of the biomethane yield from anaerobic co-digestion of nitrogenous
substrates.
AB - This paper examines three substrates for anaerobic co-digestion: abattoir waste;
cheese waste and food waste. These substrates were assessed in detail for
suitability for biomethane production. Biomethane potential (BMP) assays were
carried out in mono and co-digestion for the three substrates and two mixes: T1
(40% abattoir waste; 50% cheese waste and 10% food waste on a wet weight basis)
and T2 (30% abattoir waste; 40% cheese waste and 30% food waste). The C:N ratio
of both mixes was below optimum. Low levels suggest that the production of free
ammonia (NH3) in semi-continuous digestion was of primary concern. Both mixes
were digested in a semi-continuous process for 25 weeks. The recommended
operating condition for T1 was a loading rate of 3 kg VS mn(-3) day(-1) at a
retention time of 23 days. The biomethane yield was 305 L CH4 kg(-1) volatile
solids (VS) which was 87% of the BMP value and equivalent to 61%
biodegradability. For T2 (with the higher C:N ratio) a higher loading rate of 4kg
VS mn(-3) day(-1) at a lower retention time of 15 days was recommended. The
biomethane yield was 439 L CH4 kg(-1) VS (99% of the BMP value and 84%
biodegradibility). At these conditions, levels of total ammonical nitrogen (TAN)
were 4109 and 4831 mg L(-1) for T1 and T2, respectively. These values are on the
large side according to the literature. The temperature was reduced to 35 degrees
C to minimize toxicity associated with TAN. Ratios of volatile acids to
bicarbonate were typically in the range of 0.2-0.3 suggesting stable operation.
PMID- 24350460
TI - Enhancement of methane yield from wheat straw, miscanthus and willow using
aqueous ammonia soaking.
AB - The increasing demand for methane production cannot be satisfied by the use of
anaerobic digestion only from waste/wastewater treatment. Perennial energy crops,
such as miscanthus and willow, as well as agricultural residues can be considered
as options for increasing the methane production through biomass digestion, due
to their high organic content and biomass yield. These materials present a great
potential, which is only limited by the rigid lignocellulosic structure. In this
case, it is possible to apply a pretreatment step in order to achieve increased
biogas production. In the present study, aqueous ammonia soaking (AAS) has been
investigated as a method to disrupt the lignocellulosic structure and increase
the methane yield of wheat straw, miscanthus and willow. Among the three
biomasses tested, wheat straw and miscanthus were the most promising in terms of
methane production, yielding around 200 and 230 ml of methane per gram of total
solids. In all three cases, AAS resulted to an increase in methane yield of 37
41%, 25-27% and 94-162% for wheat straw, miscanthus and willow, respectively. A
comparison of the methane yields after 20 and 50 days of anaerobic digestion
revealed that AAS affected positively the methane production rate as well. AAS
also resulted to a low solubilization of sugars, with a 15.4% and 8.9% increase
in soluble xylose concentration in miscanthus and willow, respectively, and a 5%
solubilization of glucose in AAS-pretreated miscanthus.
PMID- 24350461
TI - Biogas production by encased bacteria in synthetic membranes: protective effects
in toxic media and high loading rates.
AB - A bioreactor including encased digesting bacteria for biogas production was
developed, and its performance in toxic media and under high organic loading
rates (OLRs) was examined and compared with traditional digestion reactors. The
bacteria (3 g) were encased and sealed in 3 x 6 cm2 PVDF (polyvinylidene
fluoride) membranes with a pore size of 0.1 microm, and then several sachets were
placed in the reactors. They were then examined in toxic medium containing up to
3% limonene as a model inhibitor in batch reactors, and OLRs of up to 20 g
COD/L.day in semi-continuous digestions. The free and encased cells with an
identical total bacterial concentration of 9 g in a medium containing 2% limonene
produced at most 6.56 and 23.06 mL biogas per day, respectively. In addition, the
digestion with free cells completely failed at an OLR of 7.5 gCOD/L.day, while
the encased cells were still fully active with a loading of 15 g COD/L x day.
PMID- 24350462
TI - Management of various organic fractions of municipal solid waste via recourse to
VFA and biogas generation.
AB - A hybrid anaerobic solid-liquid system was used for anaerobic digestion of
organic fraction of municipal solid waste (OFMSW) consisting of mixed food +
fruit waste and vegetable waste. Hydrolysis and acidogenesis potential of the
above wastes were evaluated with the aim of producing value-added products in the
form of volatile fatty acids (VFAs) and biogas recovery. Efficient hydrolysis and
acidogenesis of mixed food + fruit waste was observed at a hydraulic retention
time (HRT) of 1-3 d with a five-fold increase in soluble chemical oxygen demand
(SCOD) followed by VFA production consisting of 50-75% acetic acid. Longer time
was required for hydrolysis of vegetable waste with optimum hydrolysis and SCOD
generation at 9 d HRT followed by VFA synthesis consisting of 45% acetic acid.
Higher inoculum:substrate ratios resulted in improved hydrolysis and acidogenesis
rates for vegetable waste in shorter time of 6 d with higher VFA production and
increase in acetic acid content to 70%. When acidogenic leachate was fed into
methanogenic reactors, detectable biogas production was observed after 25 d with
37-53% SCOD removal from leachate from mixed food + fruit waste and methane
production of 0.066-0.1 L g(-1) SCOD removed and methane content of 38%. Though
biogas yield from acidogenic leachate from vegetable waste was lower, nearly 94%
volatile solids (VS) removal was observed in the reactors thereby providing
methane yield of 0.13-0.21 L g(-1) VS consumed. Thus, the study provided a method
for generation of value-added products from an otherwise misplaced resource in
the form of OFMSW.
PMID- 24350463
TI - Recovery of biogas as a source of renewable energy from ice-cream production
residues and wastewater.
AB - Proper management of waste streams and residues from agro-industry is very
important to prevent environmental pollution. In particular, the anaerobic co
digestion process can be used as an important tool for safe disposal and energy
recovery from agro-industry waste streams and residues. The primary objective of
this laboratory-scale study was to determine whether it was possible to recover
energy (biogas) from ice-cream production residues and wastewater, through a
mesophilic anaerobic co-digestion process. A high methane yield of 0.338 L
CH4/gCOD(removed) could be achieved from anaerobic digestion of ice-cream
wastewater alone, with almost 70% of methane in biogas, while anaerobic digestion
of ice-cream production residue alone did not seem feasible. When wastewater and
ice-cream production residue were anaerobically co-digested at a ratio of 9:1 by
weight, the highest methane yield of 0.131 L CH4/gCOD(removed) was observed.
Buffering capacity seemed to be imperative in energy recovery from these
substrates in the anaerobic digestion process.
PMID- 24350464
TI - The effect of solids retention time on dissolved methane concentration in
anaerobic membrane bioreactors.
AB - We assessed the effect of solids retention times (SRT) on dissolved methane
concentration in a lab-scale anaerobic membrane bioreactor (AnMBR) operated at
SRT 20d and 40d at ambient temperature (23 +/- 1 degrees C). Daily methane
production was 196 +/- 17 mL/d and 285 +/- 18 mL/d for SRT 20d and 40d,
respectively. In comparison, the average concentration of dissolved methane in
AnMBR permeates was 9.9 +/- 2.3 mg/L for SRT 20d (close to thermodynamic
equilibrium), which was decreased to 4.3 +/- 0.3 mg/L for SRT 40d. We often found
oversaturation of dissolved methane at SRT 20d, which means that mass transfer of
dissolved methane from liquid to gas phase is dynamic at this short SRT. However,
we never detected oversaturation of dissolved methane at SRT 40d, due to slow
endogenous decay kinetics. Higher daily methane production at SRT 40d than that
at SRT 20d indicates that methane was supplementarily produced from biomass
electrons by endogenous decay. This study shows that operation of AnMBRs under
long SRT can keep low dissolved methane concentration in AnMBR permeate, along
with high methane yield.
PMID- 24350465
TI - Biological pretreatment of non-flocculated sludge augments the biogas production
in the anaerobic digestion of the pretreated waste activated sludge.
AB - High-efficiency resource recovery from municipal solid waste (MSW) has been a
focus of attention. The objective of this research is to develop a bio
pretreatment process for application prior to the anaerobic digestion of MSW to
improve methane productivity. Bacillus licheniformis was used for pretreating MSW
(non-flocculated with 0.07% citric acid), followed by anaerobic digestion.
Laboratory-scale experiments were carried out in semi-continuous bioreactors,
with a total volume of 5 L and working volume of 3 L. Among the nine organic
loading rates (OLRs) investigated, the OLR of 0.84 kg SS m(-3) reactor day(-1)
was found to be the most appropriate for economic operation of the reactor.
Pretreatment of MSW prior to anaerobic digestion led to 55% and 64% increase of
suspended solids (SS) and volatile solids reduction, respectively, with an
improvement of 57% in biogas production. The results indicate that the
pretreatment of non-flocculated sludge with Bacillus licheniformis which consumes
less energy compared to other pretreatment techniques could be a cost-effective
and environmentally sound method for producing methane from MSW.
PMID- 24350466
TI - Biogas production performance of mesophilic and thermophilic anaerobic co
digestion with fat, oil, and grease in semi-continuous flow digesters: effects of
temperature, hydraulic retention time, and organic loading rate.
AB - Anaerobic co-digestions with fat, oil, and grease (FOG) were investigated in semi
continuous flow digesters under various operating conditions. The effects of
hydraulic retention times (HRTs) of 12 and 24 days, organic loading rates (OLRs)
between 1.19 and 8.97 gTVS/Ld, and digestion temperatures of 37 degrees C and 55
degrees C on biogas production were evaluated. It was proposed that, compared to
anaerobic digestion with wastewater treatment plant sludge (primary raw sludge),
semi-continuous flow anaerobic co-digestion with FOG could effectively enhance
biogas and methane production. Thermophilic (55 degrees C) co-digestions
exhibited higher biogas production and degradation of organics than mesophilic co
digestions. The best biogas production rate of 17.4 +/- 0.86 L/d and methane
content 67.9 +/- 1.46% was obtained with a thermophilic co-digestion at HRT = 24
days and OLR = 2.43 +/- 0.15 g TVS/Ld. These were 32.8% and 7.10% higher than the
respective values from the mesophilic co-digestion under similar operating
conditions.
PMID- 24350467
TI - Continuous anaerobic digestion of food waste and design of digester with lipid
removal.
AB - Separation of municipal solid waste has been implemented in many cities in China.
As a major component of municipal solid waste, food waste can be treated by
anaerobic digestion (AD) for energy production. To provide reference data for
disposing of food waste through engineering applications, continuous AD was
carried out under various organic loading rates (OLRs) at 27 +/- 2 degrees C in
the laboratory. The anaerobic reactor was stable with pH 7.0-7.1, total volatile
fatty acid (VFA) concentrations of 206-746 mg/L, and NH4+ -N concentrations of
525-1293 mg/L when the OLR was 1.118-5.588 kg volatile solids (VS)/m(3) x d. The
maximum volumetric biogas production rate was 4.41 L/L x d when the OLR was
increased to 5.588 kg VS/m(3) x d with a hydraulic retention time of 30 d. When
the OLR was increased to 6.706 and 8.382 kg VS/m(3) x d, biogas production was
seriously inhibited by VFAs, with maximum total VFA and propionate concentrations
of 8738 mg/L and 2864 mg/L, respectively. Due to the incomplete degradation of
lipids, the specific methane production rate of 353-488 L/kg VS accounted for
55.2-76.3% of the theoretical methane potential calculated based on the component
composition. A retrofitted anaerobic digester with lipid removal was designed to
improve the efficiency.
PMID- 24350468
TI - Characterization of co-digestion of industrial sludges for biogas production by
artificial neural network and statistical regression models.
AB - The characteristics and impact of industrial sludges of paper, chemical,
petrochemical, automobile, and food industries situated in the Ulsan Industrial
Complex, Ulsan, Republic of Korea in co-digestion for biogas production were
assessed by artificial neural network (ANN) and statistical regression models.
The regression model was based on a simplex-centroid mixture design and the ANN
was based on a resilient back-propagation algorithm (topology 5-7-1). Using
connection weights and bias of the trained ANN model, the impact of each sludge
of co-digestion was assessed using Garsons' algorithm. Results suggested that the
modelling and predictability of ANN were superior to the regression model with
accuracy (A(f)) 1.01, bias (B(f)) 1.00, root mean square error 3.56, and standard
error of prediction 2.51%. Sludge from the chemical industry showed the highest
impact on specific methane yield (SMY(VS)) with a relative importance of 28.59%
followed by sludges from paper (20.07%), food (19.59%), petrochemical (15.92%),
and automobile (15.82%) industries. The interactions between diverse industrial
sludges were successfully modelled and partitioned into various synergistic and
antagonistic effects on SMY(VS). Synergistic interactions between the chemical
industry sludge and either petrochemical or food industry sludges on SMY(VS) were
detected. However, strong negative interaction between automobile sludge and
other sludges was observed. This study indicates that though the ANN model
performed better in prediction and impact assessments, the regression model
reveals the synergistic and antagonistic interactions among sludges.
PMID- 24350469
TI - Application of optimized alkaline pretreatment for enhancing the anaerobic
digestion of different sunflower stalks varieties.
AB - The use of lignocellulosic residues such as sunflower stalks (SS) for the
production of bioenergy such as methane is a promising alternative to fossil
fuels. However, their recalcitrant structure justifies the use of pretreatment to
enhance the accessibility of holocelluloses and their further conversion into
methane. First, different conditions of alkaline pretreatment (i.e. duration and
NaOH concentration (g/100 g TS) at a fixed temperature of 55 degrees C) were
tested to enhance the methane potential of the stalks of the Serin sunflower (193
mL of methane per gram of volatile solids (VS)). The greatest improvement to the
methane potential (262 mL CH4 g(-1) VS) was observed at 55 degrees C, 24 h, 4 g
NaOH/100 g TS. Fourier Transform Infrared spectra highlighted an accumulation of
lignin in the digestate and the degradation of holocelluloses during the
anaerobic process, both for pretreated and untreated SS. In a second stage, this
optimum condition for alkaline pretreatment (55 degrees C, 24 h, 4 g NaOH/100 g
TS) was applied to the stalks of three other varieties of sunflower. Alkaline
pretreatment was effective in the delignification of the stalks of the different
sunflower varieties, with lignin reduction varying from 23.3% to 36.3% VS. This
reduction of lignin was concomitant with the enhancement of methane potential as
compared to that of raw SS, with an increase ranging from 29% to 44% for the
different SS.
PMID- 24350470
TI - Mesophilic co-digestion of palm oil mill effluent and empty fruit bunches.
AB - The palm oil mill industry generates palm oil mill effluent (POME) and empty
fruit bunches (EFB) as by-products. This study reports the mesophilic co
digestion of POME with EFB. The biochemical methane potential (BMP) of POME and
EFB was 0.397 L CH4/g volatile solids (VS) and 0.264 L CH4/g VS, respectively. In
a series of batch tests at various EFB to POME ratios, the maximum methane
production rate was achieved at an EFB:POME ratio of 0.25-0.31:1. Performance
data from lab-scale digesters confirmed the positive synergism by the addition of
EFB to POME, which was attributed to the balanced chemical composition, for
example the chemical oxygen demand (COD) to total Kjeldahl nitrogen (TKN) ratio.
The EFB addition enhanced the acceptable organic loading rate, methane
production, COD removal, and microbial activity. The mesophilic co-digestion of
POME and EFB promises to be a viable recycling method to alleviate pollution
problems and recover renewable energy in the palm oil mill industry.
PMID- 24350471
TI - Biocrude production by activated sludge microbial cultures using pulp and paper
wastewaters as fermentation substrate.
AB - Municipal wastewater activated sludge contains a mixed microbial community, which
can be manipulated to produce biocrude, a lipid feedstock for biodiesel
production. In this study, the potential of biocrude production by activated
sludge microorganisms grown in three different types of pulp and paper mill
wastewaters was investigated. A 20% (v/v) activated sludge was inoculated into
pulp and paper wastewater, supplemented with glucose (60 g/L) and nutrients
(nitrogen and phosphorus) to obtain a high carbon to nitrogen ratio (70:1). The
culture was incubated aerobically for seven days. The results showed that the
activated sludge microorganisms were able to grow and accumulate lipids when
cultivated in amended wastewaters. Microorganisms growing in anaerobic settling
pond effluent water showed the highest lipid accumulation of up to 40.6% cell dry
weight (CDW) after five days of cultivation compared with pulp wash wastewater
(PuWW) (11.7% CDW) and mixed wastewater (MWW) (8.2% CDW) after seven days of
cultivation. The lipids mostly contained C16-C18 fatty acids groups with oleic
acid and palmitic acid being the dominant fatty acids. The maximum biodiesel
yield was about 6-8% CDW for all the wastewaters. The results showed the
potential of utilizing pulp and paper mill effluents and other waste streams,
such as activated sludge for the sustainable production of lipids for biofuel
production.
PMID- 24350472
TI - Anaerobic digestion of crude glycerol as sole substrate in mixed reactor.
AB - Utilization of crude glycerol (CG) from the biodiesel industry in the production
of biogas offers a perspective of further energy generation, which may result
into the drop of biodiesel costs on the developing world market. This
contribution is focused on anaerobic treatment of CG as a single substrate in
mixed laboratory reactors. Experiences from long-term operation of mixed reactors
processing either untreated or acidulated CG are discussed. The possibility of
cofermentation of washing water (WW) from biodiesel production with CG was also
attempted. It was demonstrated that long-term mesophilic anaerobic treatment of
CG as the only substrate is possible. Except for nitrogen, and possibly
phosphorus, the addition of other nutrients is unnecessary. Processing of both
non-acidulated and acidulated CG in laboratory mixed reactors inoculated with
suspended sludge resulted in a stable operation with high specific methane
production (0.328 L/g chemical oxygen demand (COD) for non-acidulated CG and
0.345 L/g COD for acidulated CG), regarding organic loading rate of up to 4 g
COD/(L x d). Due to the considerable content of dissolved inorganic salts in CG
it is recommended to dilute this substrate with water to prevent the accumulation
of salts and inhibition of the biomass activity. WW was proved to be a
problematic substrate for anaerobic cofermentation with CG because its addition
to the reactor caused a decrease in the pH value and biogas production.
PMID- 24350473
TI - Optimal design of ethanol supply chains considering carbon trading effects and
multiple technologies for side-product exploitation.
AB - This work proposes a spatially explicit mixed integer linear programming
modelling framework representing the dynamic evolution of a bioethanol supply
chain (SC) under increasing biofuel demand and greenhouse gas (GHG) emission
savings over time. Key features of the proposed framework comprise: (i) the
incorporation of available set-aside rural surfaces for energy crop cultivation;
(ii) the acknowledgement ofan economic value to the overall GHG emissions through
the introduction of an Emission Trading System. Multiple technological options
are assessed to exploit the co-product Distiller's Dried Grains with Solubles
either as animal fodder (standard usage) or as fuel for heat and power generation
or as raw material for biogas production (and hence heat and power). Bioethanol
production in Northern Italy is chosen as a demonstrative case study.
PMID- 24350474
TI - Hybrid response surface methodology-genetic algorithm optimization of ultrasound
assisted transesterification of waste oil catalysed by immobilized lipase on
mesoporous silica/iron oxide magnetic core-shell nanoparticles.
AB - The production ofbiodiesel by transesterification of waste cooking oil (WCO) to
partially substitute petroleum diesel is one of the measures for solving the twin
problems of environment pollution and energy demand. An environmentally benign
process for the enzymatic transesterification using immobilized lipase has
attracted considerable attention for biodiesel production. Here, a
superparamagnetic, high surface area substrate for lipase immobilization is
evaluated. These immobilization substrates are composed of mesoporous
silica/superparamagnetic iron oxide core-shell nanoparticles. The effects of
methanol ratio to WCO, lipase concentration, water content and reaction time on
the synthesis of biodiesel were analysed by utilizing the response surface
methodology (RSM). A quadratic response surface equation for calculating fatty
acid methyl ester (FAME) content as the objective function was established based
on experimental data obtained in accordance with the central composite design.
The RSM-based model was then used as the fitness function for genetic algorithm
(GA) to optimize its input space. Hybrid RSM-GA predicted the maximum FAME
content (91%) at the optimum level of medium variables: methanol ratio to WCO,
4.34; lipase content, 43.6%; water content, 10.22%; and reaction time, 6h.
Moreover, the immobilized lipase could be used for four times without
considerable loss of the activity.
PMID- 24350475
TI - Development of a simple model for anaerobic digestion based on preliminary
measurements of the bacterial sulphur activity in wastewater stabilization ponds.
AB - The present study was undertaken to develop a simple and practical model for
anaerobic digestion, encompassing sulphate reduction and sulphur oxidation, in a
waste stabilization pond. The basic microbiological phases of the model consisted
of four processes, namely acidogenesis, methanogenesis, sulphate reduction and
sulphur oxidation. It also incorporated multiple reaction stoichiometry and
substrate utilization kinetics. The study also aimed to investigate the mutual
interaction between sulphate-reducing bacteria (SRB) and photosynthetic sulphur
bacteria (PSB) in an anaerobic sludge consortia using batch reactors. The results
revealed that for an initial concentration of sulphate ranging between 250 and
2800 mg x l(-1), SRB activity ranged between 20 and 190 mgSO4(2-)(reduced). The
gVSS(-1) x d(-1) and PSB activity varied between 60 and 320 mgSO4(2-)(produced).
gVSS(-1) x d(-1), and PSB activity was noted to be twice as high as that of SRB.
PSB can, therefore, be used effectively in the fight against odors. The most
important environmental factors affecting the sulphur cycle in the waste
stabilization pond were likely to be the availability of sulphate and light for
SRB and PSB, respectively.
PMID- 24350476
TI - Fate of heavy metals and major nutrients in a sludge-soil-plant-leachate system
during the sludge phyto-treatment process.
AB - Land application of sewage sludge usually leads to increased levels of heavy
metals in soil, plants and groundwater. Pre-treatment using plants has been
proposed to reduce the contents of heavy metals and water in sludge prior to land
application. This study quantified the transfer of Zn, Cd, Pb and major nutrients
in a sludge-soil-plant-leachate system during the treatment of sewage sludge. To
accomplish this, a two year pot experiment was carried out to collect leachate,
mono- and co-cropping of Sedum alfredii and feed crops was conducted in sludge
with an under-layer soil support. Sludge phyto-treatment increased Zn and Cd
concentrations in the under-layer soil, but not Pb. Specifically, 70%, 70% and
80% of the original Zn, Cd and Pb, respectively, remained in the sludge, while
about 40%, 70% and 60% of the original N, P and K remained. Only 3% to 5% of Cd
and Zn and < 1% of Pb were transferred into the under-layer soils or leachates,
while more than 12% of the N and P were transferred. Co-planting S. alfredii and
feed crops led to a significant reduction of heavy metals in leachates when
compared with sludge without planting. Overall, sludge leachate is more
appropriate than whole sludge for recycling in agriculture since it reduces the
chance of heavy metal contamination in the agro-ecosystem; therefore, co-cropping
phytotreatment of sludge can be coupled with sludge leachate recycling for crop
production and re-collection of the sludge residue for landfilling.
PMID- 24350477
TI - Advanced oxidation of hypophosphite and phosphite using a UV/H2O2 process.
AB - The oxidation of hypophosphite and phosphite in an aqueous solution by an
ultraviolet (UV)/H2O2 process was studied in this work. The reactions were
performed in a lab-scale batch photoreactor. The effect of different parameters
such as H2O2 dosage, H2O2 feeding mode and the initial pH of the solution on the
oxidation efficiency of the process was investigated. The results indicated that
the UV/H2O2 process could effectively oxidize hypophosphite and phosphite in both
synthesized and real wastewater. However, neither H2O2 nor UV alone was able to
appreciably oxidize the hypophosphite or phosphite. The best way of feeding H2O2
was found to be 'continuous feeding', which maximized the reaction rate. It was
also found that the process presented a wide range of applicable initial pH (5
11). When treating real rinse-wastewater, which was obtained from the electroless
nickel plating industry, both hypophosphite and phosphite were completely
oxidized within 60 min, and by extending by another 30 min, over 90% of the
chemical oxygen demand removal was obtained. Without any additional catalyst, the
UV/H2O2 process can oxidize hypophosphite and phosphite to easily removable
phosphate. It is really a powerful and environmentally friendly treatment method
for the wastewater containing hypophosphite and phosphite.
PMID- 24350478
TI - Development of porous ceramsite from construction and demolition waste.
AB - The disposal of construction and demolition (C&D) waste has become a serious
problem in China due to the rapid increase of Chinese construction industry in
recent years. In the present study, typical C&D waste was employed for ceramsite
fabrication so as to find a new way for its effective recycling. A novel process
was developed for manufacturing high-quality porous ceramsite according to the
special chemical composition and properties of C&D waste. Most importantly, a
unique bloating agent was developed for the porous structure formation since it
was difficult to obtain a suitable porous structure using traditional bloating
agents. The effects of processing parameters such as sintering temperature,
heating rate and soaking time were investigated, and the bloating mechanism for
ceramsite was discussed. The C&D waste ceramsite (CDWC), with high-intensity, low
density and homogeneous mechanical properties, was much more suitable for
application in the construction field. This study provides a practical process
for efficient recycling of the rapidly increasing quantities of C&D waste.
PMID- 24350479
TI - Phenol biodegradation by different mixed cultures and the optimization of
efficiency of the degradation.
AB - In this study, the phenol degradation capacities of four different mixed
cultures, namely, Ankara Stream (AS), petroleum-contaminated soil (PS), olive
mill wastewater (OMW), and drug mill wastewater (DMW) were investigated with
regards to different pH levels, phenol (497.2-1183.0 mg/L) and biomass
concentrations (0.5-3.0%(v/v)). The most efficient culture was selected and the
optimal conditions required for its highest performance in phenol degradation
were studied. We found 100% phenol degradation for DMW at nearly 1000 mg/L
initial concentration. The optimum pH was 8 and the mixed culture could tolerate
phenol levels up to approximately 1500 mg/L. The selected culture degraded all of
the phenol concentrations ranging from 497.2 to 1183.0 mg/L with 100% efficiency
after 48 h and 120 h incubation, respectively. Increasing the biomass
concentration from 0.5% to 3.0% (v/v) level decreased the incubation time needed
for complete degradation. The data indicate that the mixed culture used in this
study can be taken as a good candidate for effective treatment of waters
contaminated by phenol.
PMID- 24350480
TI - Optimization of marine waste based-growth media for microbial lipase production
using mixture design methodology.
AB - Lipase production by Staphylococcus xylosus and Rhizopus oryzae was investigated
using a culture medium based on a mixture of synthetic medium and supernatants
generated from tuna by-products and Ulva rigida biomass. The proportion of the
three medium components was optimized using the simplex-centroid mixture design
method (SCMD). Results indicated that the experimental data were in good
agreement with predicted values, indicating that SCMD was a reliable method for
determining the optimum mixture proportion of the growth medium. Maximal lipase
activities of 12.5 and 23.5 IU/mL were obtained with a 50:50 (v:v) mixture of
synthetic medium and tuna by-product supernatant for Staphylococcus xylosus and
Rhizopus oryzae, respectively. The predicted responses from these mixture
proportions were also validated experimentally.
PMID- 24350481
TI - Performance of 14 full-scale sewage treatment plants: comparison between four
aerobic technologies regarding effluent quality, sludge production and energy
consumption.
AB - The performance of 14 Full-Scale Sewage Treatment Plants (STPs) was evaluated.
STPs were divided into four aerobic technologies: a) Aerated Lagoon (AL), and
three configurations of activated sludge technologies, b) conventional (CAS), c)
Extended Aeration (EA), d) Sequencing Batch Reactor (SBR). Comparison between
these configurations were made regarding: a) control parameters, organic loading
rate (OLR), Mixed Liquor Volatile Suspended Solids (MLVSS) concentrations, Food
to Microorganism ratio (F/M), sludge age (theta(c)), Hydraulic Retention Time
(HRT) and return sludge ratio (R); b) effluent quality, through 5-day Biological
Oxygen Demand (BOD5), Chemical Oxygen Demand (COD), Total Suspended Solids (TSS),
Total Kjeldahl Nitrogen (TKN), Total Phosphorus (TP); and c) indicators related
to sludge production (on a dry basis) and electrical energy consumption. Also,
complementary costs analyses were made. The results show that in terms of
effluent quality, for all configurations organic matter (BOD5 and COD) and TKN
removal efficiency were up to 90%, while TSS and TP were up to 90% and 50%,
respectively. However, CAS, EA, SBR, and AL had stability problems with effluent
concentrations. The results of the electrical energy consumption and sludge
production analyses show that SBRs reduce these indicators by 40%. Cost analysis
showed that CAS, EA, SBR and AL had similar cost structures, with more than 50%
of total operating and maintenance cost being related to electrical energy and
sludge management. Therefore, SBR could be defined as the configuration with a
more stable performance.
PMID- 24350482
TI - Green energy from marine algae: biogas production and composition from the
anaerobic digestion of Irish seaweed species.
AB - Marine algae have emerged as an alternative feedstock for the production of a
number of renewable fuels, including biogas. In addition to energy potential,
other characteristics make them attractive as an energy source, including their
ability to absorb carbon dioxide (CO2), higher productivity rates than land-based
crops and the lack of water use or land competition. For Ireland, biofuels from
marine algae can play an important role by reducing imports of fossil fuels as
well as providing the necessary energy in rural communities. In this study, five
potential seaweed species common in Irish waters, Saccorhiza polyschides, Ulva
sp., Laminaria digitata, Fucus serratus and Saccharina latissima, were co
digested individually with bovine slurry. Batch reactors of 120ml and 1000ml were
set up and incubated at 35 degrees C to investigate their suitability for
production of biogas. Digesters fed with S. latissima produced the maximum
methane yield (335 ml g volatile solids(-1) (g(VS)(-1) followed by S. polyschides
with 255 ml g(VS)(-1). L. digitata produced 246ml g(VS)(-1) and the lowest yields
were from the green seaweed Ulva sp. 191ml g(VS)(-1). The methane and CO2
percentages ranged between 50-72% and 10-45%, respectively. The results
demonstrated that the seaweed species investigated are good feedstocks candidates
for the production of biogas and methane as a source of energy. Their use on a
large-scale process will require further investigation to increase yields and
reduce production costs.
PMID- 24350483
TI - Direct removal of aqueous As(III) and As(V) by amorphous titanium dioxide
nanotube arrays.
AB - Amorphous titanium dioxide nanotube arrays (TiO2 NTs) were prepared by a simple
anodization process without subsequent calcination at high temperature, and the
effectiveness of amorphous TiO2 NTs as adsorbents in removing arsenite (As(III))
and arsenate (As(V)) was investigated. The TiO2 NTs were not only effective for
arsenic removal without a pre-oxidation of As(III) to As(V) and/or adjusting the
pH value of water before the adsorption process, but also can be separated and
recovered easily from the solution. The adsorption kinetics and adsorption
capacity of the amorphous TiO2 NTs for As(III) and As(V) were studied separately
by batch experiments. The apparent values for Langmuir monolayer sorption
capacities were 28.9 mg/g for As(III) and 24.7 mg/g for As(V) at pH 7. Kinetics
studies indicated that the adsorption process on TiO2 NTs followed a pseudo
second-order kinetics model. Arsenic adsorption of TiO2 NTs remains stable over a
broad pH range. Moreover, the TiO2 NTs have excellent stability and regeneration,
and they can be used repeatedly at least five times.
PMID- 24350484
TI - Suppression of phosphorus release from sediments using water clarifier sludge as
capping material.
AB - Water clarifier sludge was assessed as a capping material for preventing release
of phosphorus from eutrophic pond sediments. Sediment incubation experiments were
carried out over two months using five capping materials (sludge, sludge sintered
respectively at 200, 400 and 600 degrees C, and sea sand) to evaluate the effect
of sintering temperature. We also examined reduction in the nitrogen eluted from
the sludge. Sludge, sludge sintered at 400 and 600 degrees C, and sea sand
suppressed phosphorus release from sediments into the overlying water, whereas
sludge and sludge sintered at 200 degrees C increased nitrogen release relative
to that without capping. Sludge sintered at 600 degrees C was the most effective
in reducing total nitrogen (TN) flux. Our experiments revealed that nitrogen and
organic substances must be removed completely from sludge in order to avoid their
release. The phosphate removal efficiency of sludge (including sintered sludge)
was expressed in terms of Freundlich adsorption isotherms. The results showed
that sludge sintered at 600 degrees C was suitable for use as a capping material
since (1) its organic content (ignition loss) and TN were low (1.1% and 0.014 mg
g(-1) dry, respectively), (2) its phosphorus adsorption capacity was 2.2 times
higher than that ofunsintered sludge, and (3) it was effective in suppressing the
diffusion of phosphorus and NH4+-N from sediments when used as a capping
material.
PMID- 24350485
TI - Surface modification of porous suspended ceramsite used for water treatment by
activated carbon/Fe3O4 magnetic composites.
AB - In this study, porous suspended ceramsite with a specific density close to that
of water was prepared by high-temperature calcination using fly ash, feldspar,
calcite, fired talc and kaolin as the raw materials. The ceramsite was modified
by activated carbon/Fe3O4 magnetic composites. The optimum modification
conditions determined by methylene blue adsorption experiment were: KOH/glucose
ratio of 1.5:1, carbonization temperature of 400 degrees C, activation
temperature of 850 degrees C, activation time of 1 h, and Fe3O4/KOH+glucose ratio
of 1:10. The results demonstrated that the adsorption capacity of the modified
ceramsite for methylene blue was significantly higher than that of the unmodified
ones. The presence of the composites did not lead to significant decrease in the
mechanical properties of the modified ceramsite. Moreover, the modified ceramsite
showed good resistance towards acid and alkali. The modified ceramsite can be
used as biocarrier and adsorbent for a wide range of contaminants in water and
can subsequently be removed from the medium by a simple magnetic procedure.
PMID- 24350486
TI - 4-nitrophenol removal from aqueous solutions by emulsion liquid membranes using
type I facilitation.
AB - Nitrophenols are common organic pollutants that enter the environment during the
manufacture and processing of a variety of industrial products. The removal of 4
nitrophenol (4NP) from aqueous solutions by emulsion liquid membranes using the
type I facilitated transport mechanism is investigated in this paper. The liquid
membrane consisted of kerosene as the organic diluent, sorbitan monooleate as the
emulsifying agent and sodium hydroxide as the stripping agent. The most important
operational variables governing the emulsion stability and the 4NP removal
process--such as the stripper agent and surfactant concentrations, the volume
ratios of membrane phase/internal phase and emulsion phase/feed phase and
stirring speed - were studied and the optimal conditions of the removal process
were experimentally determined. Apparent initial permeabilities of the transport
process in the different operational conditions were also obtained. Ninety-eight
per cent of4NP was removed in 10 minutes and an apparent initial permeability of
1.2986 min(-1) was obtained in those optimal conditions.
PMID- 24350487
TI - Ammonia removal from landfill leachate by air stripping and absorption.
AB - An old landfill leachate was pre-treated in a pilot-scale aerated packed tower
operated in batch mode for total ammoniacal nitrogen (TAN) removal. The stripped
ammonia was recovered with a 0.4 mol L(-1) H2SO4 solution, deionized water and
tap water. Ca(OH)2 (95% purity) or commercial hydrated lime was added to the raw
leachate to adjust its pH to 11, causing removal of colour (82%) and heavy metals
(70-90% for Zn, Fe and Mn). The 0.4 molL(-1) H2SO4 solution was able to
neutralize 80% of the stripped ammonia removed from 12 L of leachate. The
effectiveness of the neutralization of ammonia with deionized water was 75%.
Treating 100 L of leachate, the air stripping tower removed 88% of TAN after 72 h
of aeration, and 87% of the stripped ammonia was recovered in two 31 L pilot
scale absorption units filled with 20 L of tap water.
PMID- 24350488
TI - Removal efficiency of a constructed wetland combined with ultrasound and UV
devices for wastewater reuse in agriculture.
AB - This study evaluates the treatment efficiency of a chemical-free water treatment
for treating the secondary effluent of a municipal wastewater treatment plant
with the aim of reusing the water for agriculture. Urban wastewater was treated
by three units run in series: a full-scale horizontal sub-surface flow
constructed wetland, a small pond with an ultrasound (US) system and a UV device.
The treatment efficiency was evaluated in terms of the Italian wastewater limits
for irrigation reuse, water quality improvement (removal percentage) and algae
bloom control. The tolerable infection risk, associated with the use of
wastewaters for irrigating crops, was also assessed by applying the microbial
risk analyses proposed in the WHO guidelines for wastewater reuse. The
constructed wetland was efficient in reducing physical-chemical and
microbiological concentrations, and its efficiency was very steady over the
investigation period. The UV system significantly improved water quality (p<0.05)
in terms of pathogen concentration with a further average decrease from 0.35 to
1.23 log units, depending on the microbiological parameter. The US device was
able to prevent algae bloom on a free water surface and maintain Chlorophyll-a
concentration stable and low 2 months after activation.
PMID- 24350489
TI - Treatment of domestic wastewater using conventional and baffled septic tanks.
AB - The main theme of the study was a comparative study of domestic wastewater
treatment using conventional and baffled septic tanks. The septic tanks were fed
continuously with domestic wastewater at three different hydraulic retention
times (HRTs). The HRTs chosen were 24, 48 and 72 h with corresponding organic
loads of 0.321, 0.436 and 0.885 kg chemical oxygen demand (COD) per m3 per day,
respectively. The performance of the septic tanks at the three HRTs gave
satisfactory results. For the conventional septic tank, COD removal was 53.4%,
56% and 65.3%, at an HRT of 24, 48 and 72 h, respectively, with residual COD of
412, 380 and 334mg/l, respectively. At HRTs of 72, 48 and 24 h, the following
percentages removals were realized for: biochemical oxygen demand (BOD), 68.4%,
57, 53.5%; total suspended solid (TSS), 65.3%, 58.3, 55%; phosphorus, 29.3%,
26.9, 25.6%; total Kjeldahl nitrogen 26.8%, 20.8, 17.7%, respectively. On the
contrary, ammonia concentrations increased by 7.1%, 5.2 and 4.2% under the same
conditions. Consequently, the results showed that the removal of fecal coliform
at all HRTs was less than one log. The two baffled septic tanks exhibited
superior results at HRTs of 72, 48 and 24 h. Comparing the treated domestic
wastewater quality produced by the two types of septic tanks in terms of physico
chemical and biological characteristics, better results were obtained using the
two baffles type.
PMID- 24350490
TI - Analysis of up-flow aerated biological activated carbon filter technology in
drinking water treatment.
AB - Problems have been found in the traditional post-positioned down-flow biological
activated carbon filter (DBACF), such as microorganism leakage and low
biodegradability. A pilot test was carried out to place a BACF between the
sediment tank and the sand filter; a new technology of dual media up-flow aerated
biological activated carbon filter (UBACF) was developed. Results showed that in
terms of the new process, the up-flow mode was better than the down-flow.
Compared with the DBACF, the problem of microorganism leakage could be well
resolved with the UBACF process by adding disinfectant before the sand
filtration, and a similar adsorption effect could be obtained. For the tested raw
water, the COD(Mn) and NH3-N removal rate was 54.6% and 85.0%, respectively,
similar to the waterworks with the DBACF process. The UBACF greatly enhanced
oxygen supply capability and mass transfer rate via aeration, and the NH3-N
removal ability was significantly improved from 1.5 mg/L to more than 3 mg/L.
Influent to the UBACF with higher turbidity could be coped with through the
primary filtration of the ceramisite layer combined with fluid-bed technology,
which gave the carbon bed a low-turbidity environment of less than 1.0 NTU. The
backwashing parameters and carbon abrasion rate of the two processes were almost
the same.
PMID- 24350491
TI - Kinetics of chlorite dismutase in a perchlorate degrading reactor sludge.
AB - Kinetics of chlorite dismutase (CD), the terminal enzyme involved in the
perchlorate (ClO4(-)) reduction pathway, in a ClO4(-)-degrading bioreactor are
reported in this study. Enzyme activity was determined from dissolved oxygen
released during disproportionation of chlorite (ClO2(-)). CD activity was in the
range 29.8-36.4 U/mg dry weight sludge, and kinetic constants Vmax and K(m) of
the enzyme were 37.83 U/mg dry weight and 0.28 mM, respectively. Among reactor
operational conditions, enzyme activity was observed at pH 4.0-9.0, with an
optimum at pH 6.0. Redox potential in the range -50 to +120mV and NaCl up to 3.5
g/L had no significant effect on CD activity. However, co-occurring pollutants
such as ammonium at 10 ppm, nitrite at 50 ppm and EDTA at 100 microM reduced CD
activity substantially. The present study highlights ideal bioreactor conditions
to avoid ClO2(-) toxicity, while indicating the buffering potential of a mixed
microbial system against inhibiting factors to maintain stable CD activity in
bioreactors.
PMID- 24350492
TI - Adsorption of glycerol, monoglycerides and diglycerides present in biodiesel
produced from soybean oil.
AB - The most common methods currently used for the removal of waste glycerol,
monoglycerides and diglycerides remaining after phase separation during biodiesel
production involve wet processes. These procedures are not environmentally viable
because they require large volumes of water and thus generate significant
quantities of effluent. In this study, adsorption was employed to replace this
purification step. Some commercial activated carbons were tested along with
adsorbents chemically modified with HNO3. A kinetics study was conducted at 30
degrees C and adsorption isotherms were obtained at 20 degrees C, 30 degrees C
and 40 degrees C. The results indicated that the adsorption of glycerol increased
with the use of chemically-modified activated carbon, showing that pH has a
strong influence on glycerol adsorption. The pseudo-first-order kinetic model
provided the best fit with the experimental data for the monoglycerides while the
pseudo-second-order model showed a better fit for the glycerol and diglycerides.
The Freundlich model had the best fit with experimental data on the adsorption
equilibrium for all temperatures. The thermodynamic study indicated that the
adsorption process is endothermic and thus adsorption is favoured by increasing
the temperature. The adsorption process using chemically-modified activated
carbon was therefore very effective for the removal of waste glycerol resulting
from biodiesel production, which is of considerable significance given the legal
limits imposed.
PMID- 24350493
TI - Advanced treatment of biologically pretreated coking wastewater by a bipolar
three-dimensional electrode reactor.
AB - Electrochemical oxidation is a promising technology for the treatment ofbio
refractory wastewater. In this research, advanced treatment of coking wastewater
which had previously undergone A/O (anaerobic-aerobic biological) treatment was
investigated over Ti/RuO2 x IrO2 anode, stainless steel cathode and coke powder
particle electrodes which were packed into the electrodes in a bipolar three
dimensional electrode reactor (BTDR). The results showed that the removal
efficiency of COD and ammonia nitrogen increased with applied current density.
The main influencing factors of BTDR were evaluated by an orthogonal test,
including reaction time, plate distance, current density, plate amounts and
aeration flow rate. With reaction time of 60 min, plate distance of 1.0 cm,
current density of 20 mA/cm2 and plate amounts of four pairs, most of the
contaminants in coking wastewater can be remediated by BTDR, which can then meet
the discharge limit for coking wastewater in China. For organic pollutants, 12
kinds of organic pollutants can be completely removed, and the removal
efficiencies of 11 kinds of organic pollutants are between 13.3 and 70.3% by
advanced treatment with BTDR. We conclude that there is great potential for BTDR
in engineering applications as a final treatment for coking wastewater.
PMID- 24350494
TI - Counter-current acid leaching process for the removal of Cu, Pb, Sb and Zn from
shooting range soil.
AB - This research explores the performance of a counter-current leaching process
(CCLP) for Cu, Pb, Sb and Zn extraction in a polluted shooting range soil. The
initial metal concentrations in the soil were 1790 mg Cu/kg, 48,300 mg Pb/kg, 840
mg Sb/kg and 368 mg Zn/kg. The leaching process consisted of five one-hour acid
leaching steps, which used 1 M H2SO4 + 4 M NaCl (20 degrees C, soil suspension =
100 g/L) followed by two water rinsing steps. Ten counter-current remediation
cycles were completed and the average metal removal yields were 98.3 +/- 0.3% of
Cu, 99.5 +/- 0.1% of Pb, 75.5 +/- 5.1% of Sb and 29.1 +/- 27.2% of Zn. The
quality of metal leaching did not deteriorate throughout the 10 remediation
cycles completed for this study. The CCLP reduced acid and salt use by
approximately 68% and reduced water consumption by approximately 60%, exceeding
reductions achieved by a standard acid leaching process.
PMID- 24350495
TI - Persistent organochlorine pollutants and metals residues in sediment and
freshwater fish species cultured in a shallow lagoon, Egypt.
AB - Six freshwater fish species cultured in Lake Edku fish farm, one of the northern
Nile Delta lakes in Egypt that receives input from numerous anthropogenic
activities in addition to agriculture wastes through several huge drains, were
collected for the detection and evaluation of residues of the persistent
organochlorine (OC) pollutants polychlorinated biphenyls (PCBs), 1,1,1 -trichloro
2,2-di(4-chlorophenyl)ethane (DDT), total cyclodienes (TC),
hexachlorocyclohexanes (HCHs) and heavy metals (Cu, Cd and Pb) in their edible
parts. In all fish and sediment samples, PCBs were found in higher concentrations
than pesticides; the edible parts of Mugil capito, Tilapia galilaeus, Tilapia
zilli and Clarias lazera had the highest PCBs (3.49, 0.83, 1.06 and 4.29 ng/g wet
weight respectively), PCB 28 being most prevalent in Mugilcapito and Clarias
lazera with ratios 86 and 62%, respectively, of the total PCBs. PCB 180 was most
prevalent in Tilapia zilli (about 56% of the total PCBs). In these four fish
species OCs were found in the order: PCBs > DDTs > HCHs > TC. The other two
species (Tilapia nilotica and Tilapia aureus) had the highest concentrations of
pesticides (7.58 and 1.13 ng/g wet weight, respectively) with HCHs being most
prevalent (96% and 74% of the total pesticides, respectively). OCs were found in
the order: HCHs >> PCBs > DDTs > TC in the edible Tilapia nilotica, and in the
order: PCBs > HCHs > DDTs > TC in the other species. The mean concentrations of
PCBs and pesticides in sediments are 539.66 +/- 48.8 and 259.17 +/- 81.2 ng/g dry
weight, respectively. Among the studied metals in the edible parts of the fish
samples, about 67% of the samples contained marginally higher Pb content in the
edible parts, above the European Community's legal limit. About 50% of the
samples contained marginally higher Cd content (N.D to 0.88 microg/g) above the
permissible level of Cd in fish edible parts; the Cu content ranged from 0.37
2.36 microg/g, with a marginally higher content in the fish but below the maximum
permissible limits. As for the concentration of the studied metals in sediments
of Edku lagoon, results showed that copper had the highest concentration (2.2 +/-
0.37 microg/g) in the lake sediment.
PMID- 24350496
TI - Activated carbon prepared from yerba mate used as a novel adsorbent for removal
of tannery dye from aqueous solution.
AB - Activated carbon prepared from yerba mate (Ilex paraguariensis) was used as
adsorbent for the removal of tannery dye from aqueous solution. The activated
carbon was characterized, and it showed a mesoporous texture, with surface area
of 537.4 m2 g(-1). The initial dye concentration, contact time and pH influenced
the adsorption capacity. The equilibrium data were in good agreement with both
Langmuir and Freundlich isotherms. The adsorption kinetics of the tannery dye on
activated carbon prepared from yerba mate followed a pseudo-second-order model.
The adsorption process was found to be controlled by both external mass-transfer
and intraparticle diffusion, but the external diffusion was the dominating
process. This work highlights the potential application of activated carbon
produced from yerba mate in the field of adsorption.
PMID- 24350497
TI - Effect of hydroxyapatite, octacalcium phosphate and calcium phosphate on the auto
flocculation of the microalgae in a high-rate algal pond.
AB - Recovering microalgae is one of the main technological and economic concerns in a
high-rate algal pond (HRAP) because of their small size and their low density.
This paper emphasizes the characterization (identification and assessment of
potential flocculation) of chemical compounds involved in microalgae auto
flocculation in a HRAP. First, thermodynamic simulations were performed, using
two models (i.e. Visual Minteq and a simplified thermodynamic model) in order to
determine the chemical compounds of interest. Experimental tests were then
carried out with these compounds for assessing their flocculation ability. Both
models revealed that precipitates of calcium phosphates and their substituted
forms were the compounds involved in the auto-flocculation. Moreover,
experimental tests showed that the stoichiometric neutralization of algal charges
by calcium phosphates (i.e. hydroxyapatite (Ca5(PO4)3OH), octacalcium phosphate
(Ca4H(PO4)3) and amorphous calcium phosphate (Ca3(PO4)2)), at a pH within the
range 7-10 yields 70-82% recovered algal biomass. The optimum ratio required for
algae auto-flocculation was 0.33 Ca5(PO4)3OH/g DM(algae) at pH 10, 0.11
Ca4H(PO4)3/g DM(algae) at pH 7 and 0.23 g Ca3(PO4)2/g DM(algae) at pH 9. Auto
flocculation appears as a simple, sustainable and promising method for efficient
harvesting of microalgae in a HRAP.
PMID- 24350498
TI - Application of fluorescence in situ hybridization for the study and
characterization of nitrifying bacteria in nitrifying/denitrifying wastewater
treatment plants.
AB - The aim of this study was to verify fluorescence in situ hybridization for the
detection of nitrifying bacteria in activated sludge and biofilms, and to
determine the distribution of nitrifiers in selected wastewater treatment plants
(WWTPs). Both Czech and foreign WWTPs with intensification of nitrification (for
example, in situ bioaugmentation of nitrification or biofilms) and without
intensification were studied. The two-dimensional and three-dimensional analyses
of microscopic images were focused on quantifying the parameters and their
differences with regard to the arrangement, capacity and sludge age of the WWTPs.
This is the first time such a study has been performed in the Czech Republic.
PMID- 24350499
TI - Study of nickel and copper biosorption on brown algae Sargassum angustifolium:
application of response surface methodology (RSM).
AB - This study has been focused on the batch culture removal of Cu2+ and Ni2+ ions
from the aqueous solution using marine brown algae Sargassum angustifolium.
Influences of parameters like pH, initial metal ions concentration and biosorbent
dosage on nickel and copper adsorption were also examined using the Box-Behnken
design matrix. For biosorption of Cu2+ the optimum pH value was determined as
5.0, optimum biosorbent concentration to 1.0 g/L and optimum initial
concentration 0.15 mmol/L. For the biosorption of Ni2+, the optimal condition was
the same but the optimum pH value was determined as 6.0. Desorption experiments
indicated that CH3COOH and EDTA were efficient desorbents for recovery from Cu2+
and Ni2+. The Langmuir isotherm model was applied to describe the biosorption of
the Cu2+ and Ni2+ into S. angustifolium. The maximum uptake of Cu2+ and Ni2+ ions
by the S. angustifolium biomass under the optimal conditions was approximately
0.94 and 0.78 mmol/g dry alga, respectively. Response surface models showed that
the data were adequately fitted to a second-order polynomial model. Analysis of
variance showed a high coefficient of determination value (R2 = 0.993 for Cu2+
and 0.991 for Ni2+) and a satisfactory second-order regression model was derived.
In addition, results reported in this research demonstrated the feasibility of
employing S. angustifolium as biosorbent for Ni2+ and Cu2+ removal.
PMID- 24350500
TI - Degradation of tetracycline and sulfadiazine during continuous thermophilic
composting of pig manure and sawdust.
AB - During composting, the thermophilic phase resulted in high degradation of
antibiotics in the composting mass; thus temperature is considered as the major
factor for degradation of antibiotics. Therefore, to achieve complete removal of
antibiotics, the effect of continuous thermophilic composting on the degradation
of antibiotics and their effect on antibiotic resistant bacteria in the pig
manure were evaluated. Pig manure was mixed with sawdust, spiked with
tetracycline (10 and 100 mg/kg) and sulfadiazine (2 and 20mg/kg) on dry weight
(DW) basis and composted at 55 degrees C for six weeks. Based on the organic
decomposition, the antibiotics did not affect the composting process
significantly, but negatively influenced the bacterial population. Tetracycline
clearly exhibited a negative but marginal influence on carbon decomposition at
100 mg/kg level. The bacterial population initially decreased steeply
approximately 2 logs and slowly increased thereafter. Sulfadiazine and
tetracycline resistant bacterial populations were stable/marginally increased
after an initial decrease of about 2 or 3-5 logs, respectively. Sulfadiazine was
not detectable after three days; whereas, approximately 8% of tetracycline was
detected after 42 days of composting with a t(1/2) of approximately 11 days,
irrespective of the initial concentration. The presence of tetracycline in the
compost after 42 days of thermophilic composting indicates the involvement of a
mesophilic microbial-mediated degradation; however, further studies are required
to confirm the direct microbial involvement in the degradation of antibiotics.
PMID- 24350501
TI - Degradation of antibiotic amoxicillin using 1 x 1 molecular sieve-structured
manganese oxide.
AB - The kinetics and mechanism ofamoxicillin (AMO) degradation using a 1 x 1
molecular sieve-structured manganese oxide (MnO2) was studied. The presence of
the buffer solution (i.e., NaHCO3, NaH2PO4 and KH2PO4) diminished AMO binding to
MnO2, thus reducing AMO degradation in the pretest; therefore, all other
experiments in this study were conducted without the addition of a buffer. Third
order rate constants, second-order on AMO and first-order on MnO2 increased with
elevating pH level (2.81-7.23) from 0.54 to 9.17 M(-2) s(-1), and it decreased to
4.27 M(-2) s(-1) at pH 8.53 beyond the pk(a2) of AMO (7.3). The dissolution of
the MnO2 suspension with and without AMO exhibited a similar trend; that is, Mn2+
concentration increased with decreasing pH. However, the dissolution of MnO2 with
AMO was greater than that without AMO, except for the reaction occurring at pH
8.53, partially indicating that MnO2 acts as an oxidant in AMO degradation. The
preliminary chromatogram data display different products with varying pH reaction
s, implying that AMO elimination using this 1 x 1 molecular sieve-structured MnO2
is by adsorption as well as oxidative degradation. A complementary experiment
indicates that the amount of oxidatively degraded AMO increases substantially
from 65.5% at 4 h to 95% at 48 h, whereas the AMO adsorbed onto MnO2 decreases
slightly from 4.5% at4 h to 2.4% at 48 h. The oxidative degradation accounted for
more AMO removal than adsorption over the whole reaction course, indicating that
the oxidative reaction of AMO on MnO2 dominated the AMO removal.
PMID- 24350502
TI - An instrument to differentiate between clinical research and quality improvement.
PMID- 24350503
TI - Payment to participants in pediatric research: variation in IRB members'
attitudes.
PMID- 24350504
TI - Barriers to research on research ethics review and conflicts of interest.
PMID- 24350505
TI - Diagnosis and treatment of spondylodiscitis in HIV-positive patients.
AB - With an incidence between 1:100,000 and 1:250,000, spondylodiscitis is rare, but
is increasingly reported due to longer life expectancy, risk factors, and
comorbidities, with HIV+ patients being at greater risk. We reviewed the
literature on the diagnostic tools, and on the benefits and drawbacks of
different treatments of spondylodiscitis in HIV- positive patients. We discuss
basic strategies and indications for surgery. Recently, the trend was toward
early mobilization of patients after surgical treatment. Modern surgical and
antibiotic treatment can prevent a recurrence in these patients. The decision to
opt for conservative or surgical treatment should be made depending on the extent
of infection and the responsible pathogen, without regard to HIV. However, these
patients should be treated in a specialized hospital by an experienced
interdisciplinary team of consultants.
PMID- 24350507
TI - Complications following kyphoplasty in unstable osteoporotic vertebral body
fractures. A guide to correct fracture analysis.
AB - The possibilities offered by kyphoplasty in the treatment of osteoporotic
vertebral fractures have been widely described. Kyphoplasty is technically not
very demanding, it can be easily learned and it is minimally invasive when
compared to open surgical fracture treatment. Like many other simple surgical
methods, it has spread rapidly and as a consequence of the above factors combined
with its good reimbursement in many countries, it has experienced a widening in
the indications for which it is being employed. The intial purpose of kyphoplasty
was pain relief based on vertebral body stabilisation combined with restoration
of vertebral body height. An increasingly uncritical use of the method can be
observed and as a consequence, an increase in serious complications. During
recent years, spinal surgery departments have received an increasing number of
patients with serious complications following kyphoplasty, requiring major
reconstructive spinal surgery. On the basis of 12 cases treated over the past 36
months, we aim to provide guidelines for the indications of the kyphoplasty
procedure.
PMID- 24350506
TI - Orthopaedics and diabetes.
AB - With about 12% of orthopaedic patients being diabetic and a large proportion of
them being obese as well, orthopaedic surgeons are commonly involved in managing
diabetic patients in both outpatient and inpatient setting. This review
summarizes current concepts in diabetes management including specific orthopaedic
issues and future directions of diabetes management.
PMID- 24350508
TI - Valgus instability as a cause for recurrent lateral patellar dislocation: a new
mechanism for patellofemoral instability?
AB - An association between lateral patellar dislocation (LPD) and medial collateral
ligament injury (MCL) has recently been demonstrated on MRI. The same valgus
injury that disrupts the femoral MCL insertion can also cause a simultaneous MPFL
tear at its femoral insertion, due to the close anatomical relationship of both
ligamentous structures. Valgus laxity due to MCL-deficiency increases the Q-angle
and further adversely affects patellar stability. A knee diagnosed with a severe
MCL tear, should be evaluated for patellofemoral instability, as a temporary
patella dislocation could have been caused by the same injury and an acute LPD
indicating a tear of the MPFL can be associated with a concomitant injury of the
MCL. In case of recurrent symptoms of patellofemoral instability in a MCL
deficient knee, both the MPFL and MCL should be managed operatively. An isolated
MPFL reconstruction in this knee is likely to fail due to a persistent increase
of the Q-angle.
PMID- 24350509
TI - Anterolateral acromial approach in locking plate fixation of proximal humerus
fractures in elderly patients.
AB - We describe our experience with a two-incision anterolateral acromial approach in
locking plate fixation of proximal humeral fractures in older adults. Mean time
between injury and surgery was 3.08 +/- 1.24 days. A proximal anterolateral
transverse incision and a more distal longitudinal incision were used. A locking
plate was inserted along the lateral side of the humerus from the proximal
incision to the distal fragment of the humerus. Mean operation time was 62.37 +/-
19.05 minutes. There were no instances of axillary nerve paralysis or infection.
Postoperative imaging results were satisfactory in all cases. Three obese
patients experienced fat liquefaction at the incision site. Mean total Neer score
one year after surgery was 88.16 +/- 5.05. We conclude that the two-incision
anterolateral acromial approach with use of locking plates appears to be an
effective means to treat proximal humeral fractures in older adults.
PMID- 24350510
TI - Surgical treatment outcome for open supracondylar humerus fractures in children.
AB - Although numerous studies have been conducted on supracondylar humerus fractures
in children, there is only a limited number of studies regarding the outcome of
open fractures. In this study, the early and late outcome of open supracondylar
humerus fractures in children were evaluated. The outcome in 26 children (19
males, 7 females) treated for open supracondylar humerus fractures was evaluated
retrospectively. The mean age was 73 years (range: 4 to 14) and the mean follow
up period was 43 years (range: 2-8). According to the Gustilo-Anderson
classification, 18 patients (69%) had type 1 and 8 patients (31%) type 2 open
fractures. Nine patients (34%) presented with a nerve injury. Distal pulses could
not be detected in four patients (15%). Functional outcomes were evaluated
according to the scoring criteria by Flynn et al. Pin tract infection developed
in one patient (3%). Artery repair via an anterior approach was performed in one
patient. In nine patients with neurological symptoms, nerve functions were
restored within three to six months. The mean union time was six weeks (5-8
weeks). According to the scoring criteria by Flynn et al, an excellent outcome
was achieved in 23 patients, and a successful outcome in 3 patients. According to
these findings, although vascular and nerve injuries frequently accompany open
supracondylar humerus fractures in children, the late radiological and functional
outcome was as good as in closed fractures.
PMID- 24350511
TI - Outcome of simultaneous surgical treatment of hyperextension of
metacarpophalangeal and basal joint osteoarthritis of the thumb.
AB - The effect of correction of metacarpophalangeal (MCP) joint hyperextension on the
outcome of reconstructive surgery for basal joint osteoarthritis of the thumb was
studied. Impairment, pain and satisfaction were similar after a combined surgical
treatment of MCP hyperextension and basal thumb osteoarthritis in 33 patients, as
in a series of 233 patients at the same institution after osteoarthritis surgery
with a normal MCP joint.
PMID- 24350512
TI - Addition-subtraction osteotomy without ligamentoplasty for symptomatic trapezial
dysplasia with metacarpal instability.
AB - Trapeziometacarpal joint pain is often associated with a dynamic adduction
deformity of the thumb metacarpal, combined with radial subluxation at the base
of the thumb metacarpal, due to trapeziometacarpal dysplasia. Addition
subtraction osteotomy is a surgical option to correct the bony deformity when
conservative treatment fails. Eight patients who underwent surgery with this
technique were prospectively evaluated. All patients were female and mean age was
42 (range 27-59) years. Mean follow-up period was 23 (range 10-42) months
postoperatively. Seven patients (87.5%) were very satisfied. Joint mobility and
strength of the operated thumb was restored to a degree comparable to the
contralateral thumb. Overall function according to the Quick-DASH score improved
by 75.5% and pain according to the Visual Analogue Scale decreased by 65%.
Radiological evaluation showed a decrease of the trapezial slope. Mean angle
between the articular surface of the trapezium and the long axis of the second
metacarpal measured 1420 preoperatively 1290 and postoperatively. In the present
study results of addition-subtraction osteotomy without ligamentoplasty were
promising, especially for function and pain. The technique may be a valuable
treatment option for trapeziometacarpal dysplasia with metacarpal instability.
PMID- 24350513
TI - A comparison of ultrasonography and radiography in the management of infants with
suspected developmental dysplasia of the hip.
AB - The aim of this study was to determine the sensitivity and specificity of plain
radiography in the detection of developmental dysplasia of the hip, using hip
ultrasonography as a reference standard. A retrospective review was made in 44
infants ranging in age from 4 weeks to 50 weeks (mean age: 21.7 weeks). Both
radiographic and ultrasonographic images were obtained for 86 hips. Radiography
and ultrasonography were found to be significantly correlated in terms of
classification of developmental dysplasia of the hip presence or absence (p <
0.0001, Fisher's exact test). With ultrasonography accepted as the standard for
the diagnosis of developmental dysplasia of the hip, radiography had a
sensitivity of 61% and a specificity of 87%. The results of this study suggest
that the two imaging methods give similar overall results, but that low grade
dysplasia detected on ultrasonography may go undetected on radiography.
PMID- 24350514
TI - Early results of trabecular metal augment for acetabular reconstruction in
revision hip arthroplasty.
AB - The management of acetabular bone defects presents a challenge in revision total
hip arthroplasty (THA). The aim of this study was to assess the early clinical
and radiological outcome of revision of acetabular components using trabecular
metal cups and augments for acetabular reconstruction. The study included 18
consecutive patients with failed acetabular components after total hip
arthroplasty, with acetabular defects that were revised using porous tantalum
acetabular components and augments. The mean follow-up was 18 months (range: 12
24). At the most recent follow-up, 6 patients (33%) were graded as having an
excellent result, 9 (50%) a good result, 3 (17%) a fair result according to the
HHS. The hip centre was restored to its normal position. There were no cases of
hip dislocation. One patient had a partial sciatic nerve palsy which had resolved
two months postoperatively. Based on these early clinical and radiological
results, TM acetabular components and augments for acetabular defects (Paprosky
II and III) appear to be a promising solution for this complex situation. We
continue to monitor these patients, and a larger series with longer follow-up
will be required to determine the long-term outcome of these augments.
PMID- 24350515
TI - High flex total knee arthroplasty--a prospective, randomized study with results
after 10 years.
AB - This prospective randomized study compares the long term results between total
knee arthroplasty with a mobile bearing high flex and a fixed bearing posterior
stabilized knee (LPS) in 39 patients. The Hospital for Special Surgery score
(HSS) was calculated and radiographs in AP and lateral view were analyzed after a
minimum follow-up of 10 years. No significant differences between the two groups
were found. The mean HSS-score was 90.67 (+/- 5.75) for LPS group patients and
90.83 (+/- 8.57) points for the high flex group patients. Three patients in the
high flex group had undergone a reoperation on their knee. One knee was revised
for painful mid-flexion instability and the others for symptomatic aseptic
loosening of the tibial prosthesis. Based on these and other findings, the use of
a high flex knee system may be seriously re-considered. Further studies are
required to evaluate possible long-term adverse effects of high flex knee
systems.
PMID- 24350517
TI - Simultaneous multiple anterior cruciate ligament reconstructions using a single
Achilles tendon allograft.
AB - This study aimed to evaluate simultaneous multiple anterior cruciate ligament
(ACL) reconstructions performed with a single Achilles allograft. After selection
of an Achilles allograft with suitable length, the circumference of the isthmus
and length of the tendinous portion were measured. The Achilles tendon was
divided along its fibers into two or three strips and each strip was looped into
a two-strand construct. Fifteen Achilles allografts were used for 31 ACL
reconstructions in 30 subjects. The median circumference at the isthmus was 29 mm
and the median length of the Achilles tendon 185 mm before and 206 mm after
removal of the insertional bone block. The median difference in length before and
after removal of the bone block was 19 mm. Achilles allografts with proper length
consistently yielded two free tendon grafts suitable for simultaneous multiple
ACL reconstruction with good short-term results.
PMID- 24350516
TI - The incidence of knee and anterior cruciate ligament injuries over one decade in
the Belgian Soccer League.
AB - In an epidemiological study we assessed the evolution in the incidence and
possible risk factors of knee injuries, especially anterior cruciate ligament
(ACL) injuries, in Belgian soccer over one decade. Two soccer seasons (1999-2000
and 2009-2010) were compared and 56,364 injury reports registered by the KBVB
URBSFA were retrieved. Knee injuries totaled 9.971 cases, 5.495 in the first
season (1999-2000) and 4.476 in the second (2009-2010): a significant decrease in
incidence from 1.5 per 100 players in 2000 to 1.2 knee injuries in 2010. Six
percent of all knee injuries were ACL injuries. The reported incidence of ACL
tears slightly increased from 0.081 to 0.084 per 100 players. Female gender,
competition and age over 18 years were prognosticators for ACL injuries. Enhanced
prevention programs for ACL injuries, especially in those sports groups are
warranted.
PMID- 24350518
TI - Long-term outcome of chevron-osteotomy in juvenile hallux valgus.
AB - The long-term outcome of juvenile hallux valgus treated by a modified Austin
procedure was investigated. The clinical (subjective, AOFA Scores) and
radiological outcome (hallux valgus angles, intermetatarsal angles, position of
the sesamoid bones and metatarsal index of 15 feet in 12 patients, aged 14 years
and 2 months (SD +/- 1 year 10 months) were assessed pre- and postoperatively and
after 7 years and 3 months (SD +/- 3 years). A significant improvement of the
hallux valgus angle and of the intermetatarsal angle was obtained, persisting
until final follow-up. The mean American Orthopaedic Foot and Ankle Society
hallux metatarsophalangeal-interphalangeal and AOFA-Midfoot score were 94.5
points and 853 points, respectively. The modified Austin procedure appears to be
an effective procedure to correct a juvenile hallux valgus deformity, with long
lasting improvement, no growth disturbances and good functional outcome.
PMID- 24350519
TI - Calcaneocuboid distraction arthrodesis with allogenic bone grafting for
correction of pes planovalgus.
AB - Calcaneocuboid distraction arthrodesis is regarded as an excellent and reliable
surgical procedure for correction of pes planovalgus. Despite a potentially high
complication rate, the use of an autologous iliac crest graft is regarded as the
method of choice. In a prospective trial the results in 12 feet after
calcaneocuboid distraction arthrodesis for pes planovalgus correction with
allogenic bone graft were investigated. The mean age was 64 (52-81) years. An
angle-stable plate was generally used for fixation of the arthrodesis. Successful
bone healing was diagnosed clinically if local pain was absent during weight
bearing, forefoot manipulation and palpation. The AOFAS score improved from 58.9
(+/- 6) points preoperatively to 89.8 (+/- 6.3) points 12 months postoperatively
and the Visual Analogue Pain Scale (VAS) from 5.1 (+/- 1.4) to 0.7 (+/- 1) 12
months postoperatively. On radiological analysis, the lateral and dorsoplantar
talometatarsal axis, hindfoot axis, the navicular floor distance and
talonavicular coverage angle improved considerably. Bone fusion was observed in
11 of 12 cases postoperatively. In conclusion, the use of an allogenic graft for
calcaneocuboid distraction arthrodesis did not result in a higher pseudarthrosis
rate compared with results reported after use of an autologous iliac crest graft.
Fixation with an angle-stable plate is recommended.
PMID- 24350520
TI - Effect of shape and severity of vertebral fractures on the outcomes of
kyphoplasty.
AB - The aim of this retrospective study was to evaluate the effect of shape and
severity of osteoporotic vertebral fractures on the clinical and surgical
outcomes of kyphoplasty. Ninety-four patients with single level vertebral
fractures were enrolled. Fractures were divided into two types according to the
shape of the fractured vertebrae: wedge type (n = 54) or biconcave type (n = 40).
All fractures were further classified into 3 grades (grade 1-3) according to
their severity. The Visual Analog Score for back pain improved significantly in
the "wedge" and in the "biconcave" group: there was no significant difference
between groups. Wedge type fractures had a significantly greater correction of
anterior vertebral height and kyphotic angle than biconcave type fractures (p <
0.01). Biconcave type fractures had a significantly greater correction of the
middle vertebral height (p < 0.01), but had a higher risk of intradiscal cement
leakage (p = 0.03). Rates of cement leakage in grade 1, grade 2, and grade 3
fractures were 12.8%, 25.8%, and 50.0%, respectively : there was a gradually
higher risk of cement leakage as the severity of compression increased (p <
0.01). CONCLUSION: assessing the shape and severity of fractured osteoporotic
vertebrae gives an idea of the potential correction of body height and kyphosis,
and of the risk of cement leakage.
PMID- 24350521
TI - Factors influencing outcome of knee bone marrow oedema: a clinical study.
AB - Bone marrow oedema has a long recovery time. Conservative and surgical treatments
have been used. This study aimed at identifying a profile of patients who may
benefit from nonsurgical management. We compared the results of periodic clinical
and radiological examinations of patients who visited our clinic with knee pain
and were diagnosed with bone marrow oedema following magnetic resonance imaging
(MRI) examinations. Clinically, the patients were evaluated using the Lysholm
knee score and a visual analogue scale. The study included 67 patients (31 males,
36 females) who were followed for 6-24 months. Patient age, gender, body mass
index, affected area, and concomitant intra-articular pathology were analysed. Of
the 67 patients, 63 were treated conservatively, and four underwent
decompression. Patients with involvement of both the medial femoral condyle and
tibial plateau were found to be more resistant to treatment than those in which
only the tibial plateau was affected. Intra-articular pathologies were frequently
noted together with bone marrow oedema, causing knee pain to persist after the
bone marrow oedema had subsided.
PMID- 24350522
TI - Vitamin D insufficiency in osteoporotic hip fracture patients: rapid substitution
therapy with high dose oral cholecalciferol (vitamin D3).
AB - Assessment and treatment of osteoporosis are recommended following hip fracture.
Osteoporosis treatment assumes an adequate calcium intake and a normal vitamin D
plasma level. The authors conducted a study in three phases. Phase I: circulating
25-hydroxyvitamin D levels were retrospectively recorded from in the case records
of 381 consecutive patients with 387 hip fractures, between March 2010 and
September 2011. Only 27 patients had sufficient (> 75 nmol/L) circulating vitamin
D, and of these 22 were taking vitamin D supplements. The remainder, 354
patients, had abnormally low vitamin D levels, with a mean value of 26.4 nmol/L.
These findings confirmed literature data, and gave rise to the prospective Phase
II (October 2011): 14 consecutive patients with a hip fracture received rapid
substitution therapy with 50,000 IU cholecalciferol (vitamin D3) daily for 3
days. Patients with corrected calcium level (calcium level based on the serum
albumin level) > 2.60 mmol/L were excluded from phase II (and phase III), in
order to avoid hypercalcemia. Substitution resulted in an increase in vitamin D
plasma levels from +/- 29.6 nmol/L to +/- 81.4 nmol/L (p < 0.0001), after +/- 14
days. However, vitamin D level remained below the desired threshold of 75 nmol/L
in 29%. Therefore it was decided to increase the treatment period from 3 days to
7 days in the next 54 patients with a hip fracture in a prospective phase III
(October 2011-January 2012). This time rapid substitution resulted in an increase
from +/-31.4 nmol/L to +/-131.1 nmol/L (p < 0.0001), after +/- 16 days, and 100%
of treated patients achieved plasma levels above the desired threshold of 75
nmol/L. CONCLUSION: virtually all patients with a hip fracture have low vitamin D
plasma levels; substitution with 50,000 IU oral cholecalciferol daily for 7 days
increases vitamin D plasma levels rapidly, safely and consistently.
PMID- 24350523
TI - Vitamin D deficiency in orthopaedic patients: a single center analysis.
AB - Vitamin D is essential to bone health and is a major regulator of calcium
homeostasis. Many recent reports demonstrated worldwide high rates of vitamin D
deficiency, but few studies have been published on the vitamin D status of
orthopaedic patients. The present study aimed to investigate the extent of
hypovitaminosis D of orthopaedic patients and possible variations in vitamin D
status according to the body region which was scheduled to undergo surgery. We
measured the vitamin D level of 1119 patients consecutively admitted to an
orthopaedic surgery department of a university hospital in Germany in 2011. The
prevalence of normal (< or =30 ng/ml), insufficient (20-30 ng/ml) and deficient
(< or =20 ng/ml) 25-OH-D levels was determined. Serum Vitamin D levels and rates
of insufficiency and deficiency were compared between the different cohorts using
two-tailed tests. The level of significance was set at p < or =0.05. The serum 25
OH-D levels for all participants were normally distributed, with a mean of 2057
ng/ml. Overall, we noted an alarmingly high rate of vitamin D insufficiency or
deficiency among orthopaedic patients. No significant difference was found
related with the various body regions scheduled to undergo surgery. Given the
well-known effects of vitamin D on bone metabolism and muscle health, vitamin D
insufficiency may negatively affect patients.
PMID- 24350524
TI - Minimally invasive correction of phalangeal malunion under local anaesthesia.
AB - Posttraumatic malunion of the proximal phalanx of the fingers may cause visible
deformities and impair hand function. Severe dysfunction requires surgical
correction, most often via open corrective osteotomies. However, such an approach
requires longer bone healing time, inevitably results in a scar, and has a higher
potential for extensor tendon adhesion. When performed under general anaesthesia
it is also difficult to assess dynamic finger position such as rotational
malunion. Thus, the authors have devised and applied a technique of minimal
invasive corrective osteotomy under local anaesthesia, permitting active flexion
and extension, which leads to more accurate reduction, and earlier recovery.
PMID- 24350526
TI - An analysis of chronic kidney disease risk factors in a Louisiana nursing home
population: a cross-sectional study.
AB - BACKGROUND: Chronic Kidney Disease (CKD) and its progression are associated with
multiple risk factors. CKD is prevalent in nursing homes residents, but factors
related to CKD in this setting have not been defined. METHODS: A cross-sectional
study was conducted (n=103). Data was abstracted using standardized forms and
analyzed (SAS 9.2). Chi square and t-test statistics were used to compare
proportions and means; correlation coefficients were used to describe
associations. Logistic models were fit to the data to determine multivariate
associations. Modification of Diet in Renal Disease (MDRD) formula was used to
estimate GFR. CKD was defined according to established standards. A cutoff point
of 60 was chosen for further analysis. RESULTS: Twenty-three percent of subjects
had CKD. Mean age for eGFR <60 was 70.8 +/- 13 and for eGFR >60 was 61.7 +/-14.
Frequent co-morbidities were hypertension (75%), GERD (40%), obesity (39%),
dyslipidemia (35%), depression (34%), anemia (32%), and diabetes (32%).
CONCLUSIONS: Our population is unique in terms of its age and reasons for nursing
home admission. Factors associated with CKD in our study include age >65 years
old, being male, having a positive history of cardiovascular disease (including
congestive heart failure and coronary artery disease,) anemia, polypharmacy, and
being obese (BMI >30). Further analysis showed that age and anemia are the
strongest factors associated with CKD in our population. Management targeted at
CKD risk factor reduction may play a vital role in controlling the magnitude of
this disease. Prospective studies to investigate the relationship between gender,
a BMI greater than 30, cardiovascular disease, and CKD and its complications are
warranted.
PMID- 24350525
TI - Percutaneous radiologic gastrostomy: results and analysis of factors contributing
to complications.
AB - INTENT: Assessment of feasibility of percutaneous radiologic gastrostomy (PRG)
for long- or short-term nutritional support and analysis of attendant
complications and their underlying causes. MATERIALS AND METHODS: A retrospective
analysis of outcome, complications, and their underlying causes was carried out
in 391 patients who had percutaneous gastrostomies performed in two different
university medical centers from January 2005 to April 2010 by interventional
radiology. Forty-three were performed under general anesthesia and 348 were under
local anesthesia and conscious sedation; in 349, fluoroscopic guidance was used,
in 17 ultrasound, and in 22 CT. RESULTS: Three hundred and seventy-six procedures
were technically successful (96%). The procedure-related mortality was 2.5%.
Fifty-seven gastrostomies were removed after clinical condition of the patients
had improved. Only 36 gastrostomies remained functional for a year or longer.
Major complications attributable to PRGs occurred in 6.1% (24 of 391) of our
patients. On retrospective analysis, faulty technique may have been a major
factor in many of these 24 patients. Injuries of abdominal organs and misplaced
gastrostomies occasioned by improper localization of T fasteners were the major
culprits. Minor complications occurred in 17.6% of patients. DISCUSSION AND
CONCLUSION: Meticulous pre-procedural assessment of the topographic anatomy,
preferably by CT, is mandatory to avoid or minimize by injury of colon, spleen,
liver etc. Precise placement of T fasteners and confirmation of gastric access
under cross-table lateral fluoroscopy is necessary for proper placement of the
gastrostomy tube. Percutaneous radiologic gastrostomy has proven an excellent
technique for short- and long-term nutritional support.
PMID- 24350527
TI - Nasal tip infantile hemangioma, a case of mistaken identity.
AB - Infantile hemangioma is the most common vascular tumor in the pediatric
population, and the majority of cases are diagnosed only on history and physical
examination. This report highlights a case in which a 3-year-old girl undergoes
surgical removal of what was thought to be an infantile hemangioma.
Immunohistochemical staining, however, showed the absence of GLUT-1 marker, which
discredited the original diagnosis. The vascular tumor was found to be a unique
presentation of a pyogenic granuloma. When the clinical diagnosis is in question,
referral for biopsy may prevent unnecessary medical interventions.
PMID- 24350528
TI - Educational efforts to improve cost awareness do not reduce average drug cost per
case in adult cardiac anesthesia.
PMID- 24350529
TI - Updates for responsible sun exposure behavior and photoprotection in the south.
AB - In Louisiana, the "Sportsman's Paradise," and throughout the Southern United
States (US), outdoor pursuits are among the most popular physical activities,
despite well-documented associations between excessive solar ultraviolet (UV)
radiation and skin cancer. Although there have been recent advances in broad
spectru m sunscreens, photoprotective clothing, and photoprotective sunglasses,
few peer-reviewed publications have focused specifically on recommendations for
responsible sun behavior and photoprotection for residents of the South. In
response, the objectives of this review will be (1) to describe the adverse
health effects of excessive UV radiation exposures; (2) to review recent cohort
studies of public perceptions regarding sun behavior and photoprotection; (3) to
identify special populations at increased risks of UV-associated skin cancers;
and (4) to recommend responsible sun behavior and photoprotection strategies.
Internet search engines were queried with the key words as search terms to
examine the latest references on photoprotection and the epidemiology of UV
associated skin cancers and other adverse effects of UV-radiation exposures.
Observational studies have demonstrated that the public knows little about proper
sunscreen selection and UV protection, and cohort studies have identified
populations at increased risks of UV-associated skin cancers. Southerners should
avoid intense sunlight, wear photoprotective clothing, wear sunglasses, and
select the right sunscreen for their skin type. Physicians should counsel their
patients about responsible sun behavior and photoprotection and encourage them to
take advantage of recent advances in the development of more effective broad
spectrum sunscreens and photoprotective clothing and sunglasses for themselves
and their children.
PMID- 24350530
TI - Orlistat-induced oxalate nephropathy may be dose-independent and present as a
late manifestation.
AB - We present the case of a 61-year-old Caucasian male veteran who had been on
orlistat (120mg dosing) for four years, and had changed to the over-the-counter
(OTC) form, Alli (orlistat 60mg), about three months before presentation. He had
been experiencing nausea and vomiting for three weeks prior to evaluation.
Laboratory studies revealed a serum creatinine of 6.2 mg/dL--his previous renal
function having been normal. An ultrasound-guided renal biopsy was performed,
which revealed deposition of calcium oxalate crystals in the renal tubules.
Orlistat is a popular weight-loss medication. Orlistat-induced oxalate crystal
nephropathy has recently been reported in the literature, resulting from the
original, patented version. We report a case with the first such complication
from the OTC version, Alli - which is a reduced-dose formulation. Our case report
highlights that this complication can occur after several years of use of the
medication and is not necessarily dose dependant.
PMID- 24350531
TI - Epigastric pain in a 63-year-old woman. Atrial flutter with 2:1 atrioventricular
block; acute inferoposterior myocardial infarction.
PMID- 24350532
TI - Atypical scaphoid avascular necrosis. Right scaphoid non-union fracture with
avascular necrosis of the distal pole.
PMID- 24350533
TI - A 31-year-old man with AIDS, fever, and a rash.
PMID- 24350534
TI - Bilateral renal artery stenosis.
PMID- 24350535
TI - [Relationship between corneal thickness and postmortem interval in rabbit].
AB - OBJECTIVE: To explore the relationship between corneal thickness and postmortem
interval (PMI) in rabbit. METHODS: The rabbit model was established by air
embolism. The rabbit cornea was sampled at 6-hour-interval from 0 to 72 h
postmortem. After routine HE staining, the whole cornea image was collected by
the optical microscope. Three markers were observed including corneal epithelial
thickness (x1), corneal stromal thickness (x2) and whole corneal thickness (x3)
using Motic Images Plus 2.0 image analysis software and the data were
statistically analyzed to establish the regression function with PMI (y).
RESULTS: Within 72 h postmortem, rabbit corneal stromal thickness and whole
corneal thickness increased at 12h postmortem and reached the peak at 54h
postmortem. The two markers showed positive correlation with PMI. The regression
functions of the two markers were y = -0.070 2 x2(2) +11.398 x2 + 1634 (R2 =
0.712 2, P < 0.05) and y = -0.074 9 x3(2) +12.036 x3 + 1819.4 (R = 0.675 0, P <
0.05), respectively. CONCLUSION: The two markers of corneal stromal thickness and
the whole corneal thickness showed the strong linear correlation with PMI. The
correlation of the corneal stromal thickness is better than the whole corneal
thickness. The two markers can be used to estimate PMI.
PMID- 24350536
TI - [Bone development trend in the knee joint of Tibetan teenagers in Aba Prefecture
of Sichuan Province].
AB - OBJECTIVE: To discuss bone development trend in the knee joint of Tibetan
teenagers in Sichuan province and to effectively update the database for
estimating the living age of Tibetan teenagers in terms of bone age of the knee
joint. METHODS: Radiographs including epiphysis of distal femur, proximal tibia
and proximal fibula were taken from 483 Tibetan male and female teenagers aged
from 14 to 19 years old in Aba prefecture of Sichuan province in order to observe
epiphyseal growth situation. The descriptive data of the epiphyseal closure ages
of these teenagers' knee joints were statistically analyzed by SPSS 16.0
software. RESULTS: The distal femur epiphyseal closure occurred earliest, while
the proximal fibula epiphyseal closure occurred latest. The epiphyseal growth of
knee joints of females occurred about one year earlier than that of males.
CONCLUSION: The forensic information and data related to Tibetan teenagers' bone
age identification should be updated regularly. These results provide potential
value for the practice of forensic medicine, anthropology and clinical medicine.
PMID- 24350537
TI - Mathematical models for teenager's living age evaluation based on CT image of
medial clavicular epiphysis.
AB - OBJECTIVE: To explore the correlation between volume rendering (VR) statistics of
medial clavicular epiphysis and living age, and establish the mathematical models
for living age evaluation using the CT image of medial clavicular epiphysis based
on the growth rules of osteoepiphysis of medial clavicle. METHODS: The CT images
of the medial clavicles from 795 teenagers aged 15-25, 387 males and 408 females,
were collected in East and South China. VR 3D images were reconstructed from 0.60
mm-thick slice CT images. The epiphyseal diameter, sternal end diameter, and
their respective diameter ratio (the left: X1; the right: x3); epiphyseal area,
sternal end area, and their respective area ratio (the left: x2; the right: x4),
were measured and calculated. All these observations were analyzed using SPSS
19.0 statistical software. The statistical differences in gender and age were
analyzed by Mann-Whitney U test. The mathematical models were established using
least square. Sixty trained subjects, 30 males and 30 females, were tested to
verify the accuracy of the established mathematical models. RESULTS: In the group
of same age, x1 showed significant difference in gender; the same results were
observed in x2, x3, and x4, which suggested that the growth rules of
osteoepiphysis of medial clavicle were highly correlated with living age. The
accuracy of these mathematical models were all above 67.6% (+/- 1.0 year) and
78.5% (+/- 1.5 year). CONCLUSION: The mathematical models with reasonable
accuracy could be manageable in practice to confirm the conclusion of the atlas
method. The current study can contribute to the single skeletal age evaluation.
PMID- 24350538
TI - [Characteristics of computed dynamic posturography of patients with peripheral
vertigo].
AB - OBJECTIVE: To quantify the posture control ability of patients with peripheral
vertigo by computed dynamic posturography (CDP). METHODS: Ninety-one subjects
diagnosed with peripheral vertigo by caloric test were divided into unilateral
vestibular dysfunction group (unilateral group) and bilateral vestibular disorder
dysfunction group (bilateral group). CDP tests including sensory organization
test (SOT) and motor control test (MCT) were performed on all subjects. The CDP
results were compared with the normal data by t-test. RESULTS: In unilateral
group, there was no statistically significant difference in SOT compared with
normal data (P > 0.05). In bilateral group, the composite equilibrium score was
lower than the normal data, especially during the moving of the platform and the
changes of visual stimulation (P < 0.05). In MCT test, the latencies of both
groups showed no statistically significant difference compared with normal data
(P > 0.05). CONCLUSION: During the non-acute period of peripheral vertigo,
patients could maintain static equilibrium. Compared with normal people, dynamic
equilibrium function is normal in patients with unilateral vestibular
dysfunction, but declined in patients with bilateral vestibular dysfunction.
PMID- 24350539
TI - [Age estimation using content of sjTREC in human peripheral blood].
AB - OBJECTIVE: To determine and verify the correlation formula of age estimation
using the content of signal joint T-cell receptor excision DNA circle (sjTREC) in
human peripheral blood and to discuss its application value in forensic
biological practice. METHODS: The samples of peripheral blood stains were
collected from 30 healthy unrelated individuals whose ages were known. The DNAs
were extracted from the samples stored at room temperature after 4 weeks. The
content of sjTREC was measured by real-time fluorescent quantitative PCR
technique, and the TATA box binding protein (TBP) was selected as reference
genes. The age of each sample was predicted with the formula which was Age =
7.181 5 Y-42.458 +/- 9.42 (Y = dCtTBP-sjTREC), and the result was compared with
the real age of each individual to determine the accuracy of the formula.
RESULTS: sjTREC and TBP gene were detectable in all 30 samples of peripheral
blood. The contents of sjTREC in human peripheral blood showed a decreasing
tendency with aging. The accuracy rate for the age estimation by this method was
76.67%. CONCLUSION: The method for the age estimation with the content of sjTREC
was simple, fast, sensitive, and good species specific with important potential
application prospect.
PMID- 24350540
TI - [Determination of the biological attribute of evidence at the scene using reverse
transcription PCR and real-time fluorescent quantitative PCR].
AB - OBJECTIVE: To explore the feasibility of biological method to identify the
biological attribute of samples at crime scene. METHODS: Thirty samples of ten
blood stains, ten saliva stains and ten semen stains were selected, and all the
samples were processed by the routine method and biomolecular method,
respectively. Both RNA and DNA were isolated using DNA-RNA co-extraction
technology and the mRNA was converted into cDNA using reverse transcription PCR
(RT-PCR). Three pairs of specific primers were designed for blood stain, saliva
stain and semen stain based on the different target genes in three specific
tissues and the primers were amplified using real-time fluorescent quantitative
PCR. The differences in these biological samples were evaluated by melting
temperature (Tm) values and the size of the amplification fragment. RESULTS: The
Tm values of blood stain, saliva stain and semen stain were (84.5 +/- 0.2)
degrees C, (76.9 +/- 0.3) degrees C and (88.5 +/- 0.2) degrees C, respectively.
The length of PCR fragments of them was 177bp, 134bp and 294bp, respectively.
CONCLUSION: Compared with the routine method, RT-PCR with real-time fluorescent
quantitative PCR is highly specific, sensitive and reliable to identify the
biological attribute of evidence, and can be potentially applied to determine
evidence attribute in forensic practice.
PMID- 24350541
TI - [Difference between the cognitive and control ability and the responsibility in
forensic psychiatry evaluation].
AB - OBJECTIVE: To analyze the difference between the cognitive and control ability
and the responsibility in forensic psychiatry evaluation. METHODS: To compare the
results of the responsibility evaluation from 2001.1 to 2006.10 (the first
period) with that of the cognitive and control ability evaluation from 2006.11 to
2010.10 (the second period). The admissibility opinions on court judgment and
evaluation were investigated by return visit. The legal professions' opinions on
forensic psychiatric issues from the police office, the procuratorate, the court,
and the judiciary were investigated. RESULTS: There was no significant difference
of the criminal types between two periods (P > 0.05). There was significant
difference of the diagnostic types between two periods (P < 0.05). The proportion
of normal range and part loss of the cognitive and control ability in the second
period were higher than that in the first period, but the proportion of complete
loss of the cognitive and control ability in the second period was lower than
that in the first period (P < 0.05). Among the legal professions, 70.5% of them
thought that "the evaluation of cognitive and control ability" was different from
"the evaluation of criminal responsibility" and 94.9% of them thought that "to
confirm the influence of the forensic psychiatric evaluation of mental disorder
on the crime behavior" or "to assess of cognitive and control ability" met
requirements of normative judicial expertise. CONCLUSION: The evaluation of
cognitive and control ability is more aligned with legal requirements and
behavioral norms of own subject than the evaluation of responsibility.
PMID- 24350542
TI - [Determination of cinobufagin and resibufogenin in liver tissue by HPLC-MS/MS].
AB - OBJECTIVE: To develop a sensitive and accurate assay for detecting cinobufagin
and resibufogenin in liver tissue using high performance liquid chromatography
tandem mass spectrometry (HPLC-MS/MS). METHODS: The homogenization of liver
tissue with internal standard dexamethasone was extracted with dichloromethane.
The extracts with methanol were purified through ProElut C18 solid phase
extraction and tested in positive electrospray ionization with multiple reaction
monitoring of HPLC-MS/MS. RESULTS: The good linear relationship of cinobufagin
and resibufogenin in liver tissue were 1-204 ng/g and 1-206 ng/g, respectively.
The minimal detection threshold (S/N > or = 3) of this method was 0.3 ng/g for
both cinobufagin and resibufogenin. The matrix effect was 96.5%-126.7%. The
extraction recovery coefficient was 70.0%-82.3%. The precision of intra-day and
inter-day was less than 10%. CONCLUSION: This method is sensitive and reliable,
and can be used in forensic toxicological analysis.
PMID- 24350543
TI - [Sudden death caused by aortic dissection: 63 cases of forensic pathological
analysis].
AB - OBJECTIVE: To explore the cause of death, clinical manifestations and forensic
pathological features of death cases caused by aortic dissection. METHODS: Sixty
three cases of aortic dissection were selected from forensic medical center, Sun
Yat-sen University from 2001 to 2011 and retrospectively analyzed. RESULTS: The
patients were mostly young and middle-aged male, aged from 30 to 49 years old.
The DeBakey type II was the most common pathological type and the main cause of
death was pericardial tamponade. The most common symptom was abdominal pain.
However, the location of aorta dissection did not always correlate with the
location of pain. Some cases showed no obvious clinical symptoms. The rupture was
usually located in ascending aorta with atherosclerosis and pathological changes
of hypertension. CONCLUSION: It is significant for diagnosis and evaluation the
cause of death of aortic dissection by knowing the clinical symptoms and forensic
pathological features.
PMID- 24350544
TI - [Disability appraisal for common peroneal nerve injury in traffic accidents: 8
cases analysis].
AB - OBJECTIVE: To investigate the characteristics of forensic clinical identification
on common peroneal nerve injury in traffic accident. METHODS: Eight cases of
common peroneal nerve injury in traffic accidents were analyzed, including
general condition of the wounded, the way of injury, the imaging results, the EMG
results, and the degree of injury, etc. RESULTS: In 8 cases, 2 cases of complete
common peroneal nerve injury were determined to grade 9 (disability degree) and 6
cases of partial common peroneal nerve injury were determined to grade 10
(disability degree). CONCLUSION: By comparison, the disability degree of complete
common peroneal nerve injury is higher than that of partial common peroneal nerve
injury. The forensic clinical identification of common peroneal nerve should be
made with synthetical consideration of medical history, symptoms, and auxiliary
examinations.
PMID- 24350545
TI - [Characteristics of recidivism in patients with mental disorders: 156 cases
analysis].
AB - OBJECTIVE: To analyze the characteristics of recidivism in patients with mental
disorders, including criminology, clinic and guardianship, in order to provide
references for preventing recidivism. METHODS: Using the self-designed
questionnaire, 156 psychotic patients who had repeated crimes were appraised by
West China Forensic Science Center of Sichuan University from 2007 to 2011 and
the data were collected and analyzed. RESULTS: In the majority of these cases,
patients were male, 26-45 years old, junior high school or below diploma,
unmarried, and farmers or jobless. Each patient broke law 3.26 times on average.
The main crimes were intentional injury (34.6%) and murder (15.7%). Within 5
years after diagnosis with mental disorder, 56.4% of the patients committed first
crime. Within 1 year after the first time breaking the law, 55.8% of them
repeated crimes. The diagnoses of schizophrenia (63.5%) were in the majority. The
assessment results were mostly irresponsibility (61.5%). Among the patients,
44.9% of them didn't receive treatment while 34.6% of them were out of
supervision. After the first crime, 66.1% of them didn't receive criminal
prosecution while only 7.1% of them went through the appraisement of forensic
psychiatry. CONCLUSION: Most of the patients had low education and low income.
Meanwhile, low outpatient rate and pool supervision occurred in this special
crowd. A good system for care and treatment of these mental patients should be
built to prevent them from recidivism.
PMID- 24350546
TI - [Genetic polymorphisms of 16 STR loci in Tibetan Mastiff].
AB - OBJECTIVE: To explore the genetic polymorphisms of 16 STR loci from 449 Tibetan
Mastiffs in order to set up gene polymorphism database of Tibetan Mastiff.
METHODS: The PCR amplification was performed using the 16 STR loci fluorescent
multiple amplification kit for dog. The amplified products were detected and
statistically analyzed. RESULTS: In the 16 STR loci from 449 Tibetan Mastiffs,
CDP was 0.999 999 999 999 999 and CEP was 0.999 997 795. Except FH2010 (10
alleles), PEZ21 (12 alleles), and PEZ05 (13 alleles), the other STR loci had more
than 15 alleles. In the 16 STR loci, H was > 0.5 and PIC was > 0.7. CONCLUSION:
The 16 STR loci have high polymorphism to be suitable for individual
identification and paternity testing of Tibetan Mastiff. The data obtained
through this study can be used to establish DNA polymorphism database of Tibetan
Mastiff.
PMID- 24350547
TI - [Multifocal visual electrophysiology in visual function evaluation].
AB - Multifocal visual electrophysiology, consisting of multifocal electroretinography
(mfERG) and multifocal visual evoked potential (mfVEP), can objectively evaluate
retina function and retina-cortical conduction pathway status by stimulating many
local retinal regions and obtaining each local response simultaneously. Having
many advantages such as short testing time and high sensitivity, it has been
widely used in clinical ophthalmology, especially in the diagnosis of retinal
disease and glaucoma. It is a new objective technique in clinical forensic
medicine involving visual function evaluation of ocular trauma in particular.
This article summarizes the way of stimulation, the position of electrodes, the
way of analysis, the visual function evaluation of mfERG and mfVEP, and discussed
the value of multifocal visual electrophysiology in forensic medicine.
PMID- 24350548
TI - [Reflection of estimating postmortem interval in forensic entomology and the
Daubert standard].
AB - Estimating postmortem interval (PMI) is always the emphasis and difficulty in
forensic practice. Forensic entomology plays a significant indispensable role.
Recently, the theories and technologies of forensic entomology are increasingly
rich. But many problems remain in the research and practice. With proposing the
Daubert standard, the reliability and accuracy of estimation PMI by forensic
entomology need more demands. This review summarizes the application of the
Daubert standard in several aspects of ecology, quantitative genetics, population
genetics, molecular biology, and microbiology in the practice of forensic
entomology. It builds a bridge for basic research and forensic practice to
provide higher accuracy for estimating postmortem interval by forensic
entomology.
PMID- 24350549
TI - Quality control system of judicial expertise in China.
PMID- 24350550
TI - Symposium introduction: challenges of intergovernmental management.
PMID- 24350551
TI - Comparative federal health care policy: evidence of collaborative federalism in
Pakistan and Venezuela.
AB - Collaborative federalism has provided an effective analytical foundation for
understanding how complex public policies are implemented in federal systems
through intergovernmental and intersectoral alignments. This has particularly
been the case in issue areas like public health policy where diseases are
detected and treated at the local level. While past studies on collaborative
federalism and health care policy have focused on federal systems that are
largely democratic, little research has been conducted to examine the extent of
collaboration in authoritarian structures. This article applies the collaborative
federalism approach to the Islamic Republic of Pakistan and the Bolivarian
Republic of Venezuela. Evidence suggests that while both nations have exhibited
authoritarian governing structures, there have been discernible policy areas
where collaborative federalism is embraced to facilitate the implementation
process. Further, while not an innate aspect of their federal structures,
Pakistan and Venezuela can potentially expand their use of the collaborative
approach to successfully implement health care policy and the epidemiological
surveillance and intervention functions. Yet, as argued, this would necessitate
further development of their structures on a sustained basis to create an
environment conducive for collaborative federalism to flourish, and possibly
expand to other policy areas as well.
PMID- 24350552
TI - Assessment of pandemic preparedness in a socially vulnerable community in south
Texas.
AB - The purpose of this research was to obtain information about general and pandemic
preparedness efforts of residents within San Patricio County in South Texas, as
well as to identify the most effective means of communicating the risks posed by
pandemic influenza. The population of San Patricio County is socially vulnerable
to a variety of disasters, including influenza pandemics due to the unique
demographic profile of the county as well as its location on the Gulf Coast. The
goals of this study were to help with pandemic planning efforts and to provide
recommendations that could serve as a foundation for building more resilient
communities within San Patricio County. Clearly the various governmental levels
must work together to assist communities prepare for pandemic preparedness but
broad, inclusive community participation is also necessary to strengthen
community resilience.
PMID- 24350553
TI - Decisional inconsistencies in the management of contaminated, sport-caught fish.
AB - Persistent toxic pollutants such as polychlorinated biphenyls and mercury
accumulate in tissues of fish that are caught and consumed by sport anglers and
their families. Unlike commercially-sold fish, the U.S. Food and Drug
Administration (FDA) does not regulate sport-caught fish that are contaminated
with these and other pollutants. Instead, nearly every state in the U.S. develops
and issues consumption advice for contaminated sport-caught fish. We examined
fish consumption advice issued by states that border and share waters of the
Mississippi River. Our examination identified numerous jurisdictional
inconsistencies that threaten the receptivity and credibility of consumption
advice and, more important, threaten the health of individuals who consume
contaminated sport-caught fish.
PMID- 24350554
TI - Faith-based partnerships and foster parent satisfaction.
AB - Throughout the last several decades, there has been a chronic shortage of foster
and adoptive families in the United States. Recruiting families to begin the
licensure process to become foster and adoptive parents is already a difficult
undertaking. But research shows that a very large proportion of families drop out
of the licensure process early on due to frustration or a lack of support. This
paper studies two faith-based partnerships that have arisen to create new
capacity in the child welfare system. These programs recruit prospective families
from churches and then provide training and ongoing support to those families
throughout the licensure process. Using survey data collected from program
participants, respondent perceptions of the licensure process are compared to a
nationally representative sample of foster parents from the National Foster Care
Adoptions Attitude Survey. Statistical results demonstrate that participants with
the faith-based programs reported much higher levels of satisfaction with the
process than the national sample. These findings provide evidence that these
faith-based partnerships may provide an important additional source of capacity
for an overburdened child welfare system.
PMID- 24350555
TI - Future directions in intergovernmental relations.
PMID- 24350556
TI - Strong and anisotropic superexchange in the single-molecule magnet (SMM)
[MnIII(6)OsIII]3+: promoting SMM behavior through 3d-5d transition metal
substitution.
AB - The reaction of the in situ generated trinuclear triplesalen complex [(talent
Bu2)MnIII3(solv)n]3+ with (Ph4P)3[OsIII(CN)6] and NaClO4.H2O affords
[MnIII6OsIII](ClO4)3 (= [{(talent-Bu2)MnIII3}2{OsIII(CN)6}](ClO4)3) in the
presence of the oxidizing agent [(tacn)2NiIII](ClO4)3 (tacn =1,4,7
triazacyclononane), while the reaction of [(talent-Bu2)MnIII3(solv)n]3+ with
K4[OsII(CN)6] and NaClO4.H2O yields [MnIII6OsII](ClO4)2 under an argon
atmosphere. The molecular structure of [MnIII6OsIII]3+ as determined by single
crystal X-ray diffraction is closely related to the already published
[MnIII6Mc]3+ complexes (Mc = CrIII, FeIII, CoIII, MnIII). The half-wave potential
of the OsIII/OsII couple is E1/2 = 0.07 V vs Fc+/Fc. The FT-IR and electronic
absorption spectra of [MnIII6OsII]2+ and [MnIII6OsIII]3+ exhibit distinct
features of dicationic and tricationic [MnIII6Mc]n+ complexes, respectively. The
dc magnetic data (MUeff vs T, M vs B, and VTVH) of [MnIII6OsII]2+ are
successfully simulated by a full-matrix diagonalization of a spin-Hamiltonian
including isotropic exchange, zero-field splitting with full consideration of the
relative orientation of the D-tensors, and Zeeman interaction, indicating
antiferromagnetic MnIII-MnIII interactions within the trinuclear triplesalen
subunits (JMn-Mn(1) = -(0.53 +/- 0.01) cm-1, Hex = -2?i=10 cm, presence of lymph node metastasis and main
portal vein tumour thrombosis compared to the TACE+RT group. The OS in the
TACE+RT group was significantly longer compared to the sorafenib group (14.1
months vs. 3.3 months, P < 0.001). In the propensity score-matched cohort,
baseline characteristics did not differ between the two groups. The TACE+RT group
showed prolonged OS compared to the sorafenib group (6.7 months vs. 3.1 months, P
< 0.001). Multivariate analysis revealed that TACE+RT was the only independent
prognostic factor associated with survival in the propensity score-matched cohort
(HR = 0.172, P < 0.001). CONCLUSIONS: The OS of TACE+RT was longer compared to
sorafenib treatment in locally advanced HCC patients without distant metastasis.
Further prospective studies are warranted to confirm these findings.
PMID- 24350565
TI - Interaction between RB protein and NuMA is required for proper alignment of
spindle microtubules.
AB - Retinoblastoma protein (pRB) controls cell cycle progression and cell cycle exit
through interactions with cellular proteins. Many pRB-binding proteins, which
function in gene transcription or modulation of chromatin structure, harbor LXCXE
motifs in their binding domain for pRB. In this study, we found that nuclear
mitotic apparatus protein (NuMA), a mitotic spindle organizer, interacts with pRB
through LSCEE sequences located in its C-terminal region. siRNA-mediated down
regulation of pRB caused aberrant distribution of NuMA and alignment of spindle
microtubules in mitotic cells. Abnormal organization of spindle microtubules was
also accompanied by misalignment of an over-expressed NuMA mutant (mut-NuMA) with
a defect in pRB binding caused by an LSGEK mutation. The mut-NuMA-over-expressing
cells showed lower potency for survival than wild-type NuMA (wt-NuMA)-over
expressing cells during 2 weeks of culture. Interestingly, knockdown of pRB
reduced the population of wt-NuMA-over-expressing cells to the same level as mut
NuMA cells after 2 weeks. Taken together, pRB may have a novel function in
regulating the mitotic function of NuMA and spindle organization, which are
required for proper cell cycle progression.
PMID- 24350566
TI - Comparison of collagen membrane and bone substitute as a carrier for rhBMP-2 in
lateral onlay graft.
AB - OBJECTIVES: To evaluate the bone regenerative effect of bioresorbable collagen
membrane (CM) as a carrier for recombinant human bone morphogenetic protein-2
(rhBMP-2) when performing lateral onlay grafts using bovine hydroxyapatite
incorporated with collagen matrix (BHC) in combination with CM in dogs. MATERIAL
AND METHODS: A guided bone regeneration (GBR) was performed at the buccal aspect
of edentulous maxillary alveolar ridges in dogs (n = 5): (1) BHC group, in which
rhBMP-2-loaded BHC was covered by a CM, and (2) CM group, in which BHC was
covered by an rhBMP-2-loaded CM. A histologic and histometric analysis was
performed after 8 weeks of healing. RESULTS: Both the BHC and CM groups exhibited
substantial newly formed bone (NB). More NB was found in the CM group than in the
BHC group without statistical significance. Most of the NB was in direct contact
with the residual bone substitute in the BHC group, whereas the projections and
islands of NB were observed in the spaces between the residual bone substitute
clusters in the CM group. The bone-to-residual bone substitute contact ratio was
significantly lower in the CM group than in the BHC group (P = 0.043).
CONCLUSIONS: Within the limitations of this study, it can be concluded that rhBMP
2-loaded CM performed lateral onlay grafts as effectively as rhBMP-2-loaded BHC
while showing less bone-residual bone substitute contact ratio in dogs. The
loading of CMs with rhBMP-2 might therefore be a recommendable treatment option
for facilitating lateral onlay graft combined with rhBMP-2.
PMID- 24350568
TI - Mental pain, communication difficulties, and medically serious suicide attempts:
a case-control study.
AB - Medical severe suicide attempts (MSSA) are epidemiologically very similar to
individuals who complete suicide. Thus the investigation of individuals who have
made MSSAs may add to our understanding of the risk factors for completed
suicide. The aim of this study was to assess the role of mental pain and
communication difficulties in MSSA. A total of 336 subjects were divided into 4
groups: 78 meeting criteria for MSSA compared with116 subjects who made a
medically non-serious suicide attempt (MNSSA), 47 psychiatric controls with no
history of suicidal behavior, and 95 healthy controls. Mental pain variants
(e.g., hopelessness), facets of communication difficulties (e.g., self
disclosure), as well as socio-demographic and clinical characteristics were
assessed. The MSSA had significantly higher communication difficulties than the
other 3 groups. Moreover, the interaction between mental pain and communication
difficulties explained some of the variance in suicide lethality, above and
beyond the contribution of each component alone. This report underlines the
importance of mental pain for suicide attempts in general while difficulties in
communication abilities play a critical role in differentiating MSSA from MNSSA.
The co-existence of unbearable mental pain with difficulties in communication
significantly enhances the risk for more lethal forms of suicidal behavior.
PMID- 24350567
TI - Controlled multiple growth factor delivery from bone tissue engineering scaffolds
via designed affinity.
AB - It is known that angiogenesis plays an important role in bone regeneration and
that release of angiogenic and osteogenic growth factors can enhance bone
formation. Multiple growth factors play key roles in processes that lead to
tissue formation/regeneration during natural tissue development and repair.
Therefore, treatments aiming to mimic tissue regeneration can benefit from
multiple growth factor release, and there remains a need for simple clinically
relevant approaches for dual growth factor release. We hypothesized that mineral
coatings could be used as a platform for controlled incorporation and release of
multiple growth factors. Specifically, mineral-coated scaffolds were "dip coated"
in multiple growth factor solutions, and growth factor binding and release were
dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate
(beta-TCP) scaffolds were fabricated using indirect solid-free form fabrication
techniques and coated with a thin conformal mineral layer. Mineral-coated beta
TCP scaffolds were sequentially dipped in recombinant human vascular endothelial
growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral
binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for
the incorporation of each growth factor. The dual release profile showed
sustained release of both growth factors for over more than 60 days. Scaffolds
releasing either rhVEGF alone or the combination of growth factors showed an
increase in blood vessel ingrowth in a dose-dependent manner in a sheep
intramuscular implantation model. This approach demonstrates a "modular design"
approach, in which a controllable biologics carrier is integrated into a
structural scaffold as a thin surface coating.
PMID- 24350569
TI - Preliminary experience with stenting for management of non-urolith urethral
obstruction in eight cats.
AB - OBJECTIVE: To (1) describe minimally invasive transurethral antegrade and
retrograde techniques for the placement of self-expanding metallic stents (SEMS)
to reestablish urethral patency in cats with non-urolith urethral obstructions
and (2) to report the procedural complications, incontinence rates, and long-term
effectiveness in maintaining a patent urethra. STUDY DESIGN: Case series.
ANIMALS: Cats (n = 8). METHODS: Signalment, history, clinical signs, physical
examination, severity of stranguria and incontinence, clinicopathologic data,
diagnostic procedures performed, diagnosis, interventional technique, type and
dimensions of stent placed, complications and final outcome of 8 cats treated
with SEMS for the management of urethral strictures or masses are presented. Each
cat was followed for >=12 months. Follow-up information was obtained from the
medical record or by telephone interview of the owner and/or referring
veterinarian. RESULTS: Four cats were continent after stent placement, 2 were
moderately incontinent, and 2 were severely incontinent. Long-term follow-up
(median, 462 days) was available. At follow-up, 5 cats were alive and 3 had been
euthanatized at 88, 233, and 305 days. Long-term outcome, as assessed by the
authors, was good (1) to excellent (3) in 4 cats, and fair (2) to poor (2) in 4
cats. Owner reported outcomes were excellent in 3/8, good to excellent in 1/8,
good in 2/8, and poor in 2/8. CONCLUSION: Palliative stenting of urethral
obstructions is a minimally invasive method to re-establish urethral patency in
cats.
PMID- 24350570
TI - Attachment insecurities and women's sexual function and satisfaction: the
mediating roles of sexual self-esteem, sexual anxiety, and sexual assertiveness.
AB - We examined the potential role of three mediators--sexual self-esteem, sexual
anxiety, and sexual assertiveness--of the association between romantic attachment
insecurities (anxiety and avoidance) and two aspects of women's sexual
functioning: sexual function and sexual satisfaction. A sample of 556 women aged
18 to 30 agreed to complete an online series of validated questionnaires
assessing attachment insecurities and several aspects of sexual functioning.
Lower sexual self-esteem and higher sexual anxiety mediated the associations
between attachment anxiety and lower sexual function and satisfaction. Lower
sexual self-esteem and higher sexual anxiety also partially mediated the links
between attachment-related avoidance and the two sexual functioning variables.
Sexual assertiveness, however, did not mediate these associations. A significant
interaction between attachment anxiety and avoidance was also found to predict
sexual satisfaction, with women high in avoidance and low in anxiety being the
least satisfied. Results are discussed in terms of theoretical and clinical
implications.
PMID- 24350571
TI - Parental depression and child conduct problems: evaluation of parental service
use and associated costs after attending the Incredible Years Basic Parenting
Programme.
AB - BACKGROUND: There is co-morbidity between parental depression and childhood
conduct disorder. The Incredible Years (IY) parenting programmes reduce both
conduct disorder in children and depression in their parents. Recent U.K. and
Ireland trials of the effectiveness and cost-effectiveness of IY parenting
programmes have assessed children's health and social care service use, but
little is known about the programme's impact on parental service use. This paper
explores whether an above clinical cut-off score on the Beck Depression Inventory
II (BDI II) is associated with high or low parental health and social care
service use in high-risk families receiving the IY Basic Programme. METHODS: This
is a secondary analysis of a subsample (N = 119) from the first U.K. community
based randomised controlled trial of the 12-week IY Basic Programme (N = 153).
Parents with children at risk of developing conduct disorder were randomised to
receive the programme or to a waiting-list control group. BDI II total and BDI II
clinical depression cut-off scores were compared to frequencies and costs of
parents' service use, at baseline, six, twelve and eighteen months post-baseline
for the intervention group and at baseline and six months post-baseline for the
control group. RESULTS: Intervention group parents who scored above the clinical
cut-off on the BDI II at baseline used more health and social care services than
those who scored below at baseline, six and eighteen months. Significant
reductions in service use frequencies were found for the intervention group only.
CONCLUSION: Parents with higher levels or depression used more health and social
care service and parenting programmes have been shown to reduce parental
depression and also health and social service use. However, further exploration
of depressed parents' service use and the cost implications for publically funded
health and social care services is needed.
PMID- 24350572
TI - Predictability and irreversibility of genetic changes associated with flower
color evolution in Penstemon barbatus.
AB - Two outstanding questions in evolutionary biology are whether, and how often, the
genetic basis of phenotypic evolution is predictable; and whether genetic change
constrains evolutionary reversibility. We address these questions by studying the
genetic basis of red flower color in Penstemon barbatus. The production of red
flowers often involves the inactivation of one or both of two anthocyanin pathway
genes, Flavonoid 3',5'-hydroxylase (F3'5'h) and Flavonoid 3'-hydroxylase (F3'h).
We used gene expression and enzyme function assays to determine that redundant
inactivating mutations to F3'5'h underlie the evolution of red flowers in P.
barbatus. Comparison of our results to previously characterized shifts from blue
to red flowers suggests that the genetic change associated with the evolution of
red flowers is predictable: when it involves elimination of F3'5'H activity,
functional inactivation or deletion of this gene tends to occur; however, when it
involves elimination of F3'H activity, tissue-specific regulatory substitutions
occur and the gene is not functionally inactivated. This pattern is consistent
with emerging data from physiological experiments indicating that F3'h may have
pleiotropic effects and is thus subject to purifying selection. The multiple,
redundant inactivating mutations to F3'5'h suggest that reversal to blue-purple
flowers in this group would be unlikely.
PMID- 24350573
TI - The bacterial communities in plant phloem-sap-feeding insects.
AB - The resident microbiota of animals represents an important contribution to the
global microbial diversity, but it is poorly known in many animals. This study
investigated the bacterial diversity in plant phloem-sap-feeding whiteflies,
aphids and psyllids by pyrosequencing bacterial 16S rRNA gene amplicons. After
correction for sequencing error, just 3-7 bacterial operational taxonomic units
were recovered from each insect sample sequenced to sufficient depth for
saturation of rarefaction curves. Most samples were dominated by primary and
secondary symbionts, which are localized to insect cells or the body cavity,
indicative of a dearth of bacterial colonists of the gut lumen. Diversity indices
of the bacterial communities (Shannon's index: 0.40-1.46, Simpson's index: 0.15
0.74) did not differ significantly between laboratory and field samples of the
phloem-feeding insects, but were significantly lower than in drosophilid flies
quantified by the same methods. Both the low bacterial content of the phloem sap
diet and biological processes in the insect may contribute to the apparently low
bacterial diversity in these phloem-feeding insects.
PMID- 24350574
TI - Variational attenuation correction in two-view confocal microscopy.
AB - BACKGROUND: Absorption and refraction induced signal attenuation can seriously
hinder the extraction of quantitative information from confocal microscopic data.
This signal attenuation can be estimated and corrected by algorithms that use
physical image formation models. Especially in thick heterogeneous samples,
current single view based models are unable to solve the underdetermined problem
of estimating the attenuation-free intensities. RESULTS: We present a variational
approach to estimate both, the real intensities and the spatially variant
attenuation from two views of the same sample from opposite sides. Assuming noise
free measurements throughout the whole volume and pure absorption, this would in
theory allow a perfect reconstruction without further assumptions. To cope with
real world data, our approach respects photon noise, estimates apparent bleaching
between the two recordings, and constrains the attenuation field to be smooth and
sparse to avoid spurious attenuation estimates in regions lacking valid
measurements. CONCLUSIONS: We quantify the reconstruction quality on simulated
data and compare it to the state-of-the art two-view approach and commonly used
one-factor-per-slice approaches like the exponential decay model. Additionally we
show its real-world applicability on model organisms from zoology (zebrafish) and
botany (Arabidopsis). The results from these experiments show that the proposed
approach improves the quantification of confocal microscopic data of thick
specimen.
PMID- 24350575
TI - Introducing palliative care into entry-level physical therapy education.
AB - BACKGROUND AND OBJECTIVE: There is a paucity of information related to teaching
palliative care to entry-level physical therapy students. The aim of this study
was to evaluate the impact of an undergraduate course in palliative care on the
preparedness of entry-level physical therapy students to practice within the
palliative care setting. METHODS: Participants were all entry-level undergraduate
students enrolled in the third year of a 4-year undergraduate degree. All
students enrolled in the course, "Physiotherapy Through Lifestages" took part in
the learning modules relating to the care of patients undergoing palliative care.
A survey instrument was used in the study, a modified version of an existing
unpublished written questionnaire previously used to evaluate palliative care
education in other allied health professions. RESULTS AND CONCLUSIONS:
Participation in the course resulted in an increase in self-rated knowledge and
confidence for working in the palliative care setting for entry-level physical
therapy students and is considered to provide a useful ongoing resource for the
presentation of this topic material. Although the impact of the delivery of this
education module may be considered successful in this regard, it would appear
that some of the underlying attitudes and emotional responses to this area of
physiotherapy practice were less easily influenced. Further research is required
to understand the influences on emotional preparedness of students to undertake
this area of study and practice and to determine the optimal stage of study for
delivery of this content.
PMID- 24350576
TI - Association of microRNA-126 expression with clinicopathological features and the
risk of biochemical recurrence in prostate cancer patients undergoing radical
prostatectomy.
AB - OBJECTIVE: Numerous studies have suggested that microRNA-126 (miR-126) is
involved in development of various cancer types as well as in malignant
proliferation and invasion. However, its role in human prostate cancer (PCa) is
still unclear. The aim of this study was to investigate miR-126 expression in PCa
and its prognostic value for PCa patients undergoing radical prostatectomy.
METHODS: A series of 128 cases with PCa were evaluated for the expression levels
of miR-126 by quantitative reverse-transcription PCR (qRT-PCR). Kaplan-Meier
analysis and Cox proportional hazards regression models were used to investigate
the correlation between miR-126 expression and prognosis of PCa patients.
RESULTS: Compared with non-cancerous prostate tissues, the expression level of
miR-126 was significantly decreased in PCa tissues (PCa vs. non-cancerous
prostate: 1.05 +/- 0.63 vs. 2.92 +/- 0.98, P < 0.001). Additionally, the loss of
miR-126 expression was dramatically associated with aggressive clinical
pathological features, including advanced pathological stage (P = 0.001),
positive lymph node metastasis (P = 0.006), high preoperative PSA (P = 0.003) and
positive angiolymphatic invasion (P = 0.001). Moreover, Kaplan-Meier survival
analysis showed that PCa patients with low miR-126 expression have shorter
biochemical recurrence (BCR)-free survival than those with high miR-126
expression. Furthermore, multivariate analysis indicated that miR-126 expression
was an independent prognostic factor for BCR-free survival after radical
prostatectomy. CONCLUSION: These findings suggest for the first time that the
loss of miR-126 expression may play a positive role in the malignant progression
of PCa. More importantly, the downregulation of miR-126 may serve as an
independent predictor of BCR-free survival in patients with PCa. VIRTUAL SLIDES:
The virtual slide(s) for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1740080792113255.
PMID- 24350577
TI - The impact of economic factors on migration considerations among Icelandic
specialist doctors: a cross-sectional study.
AB - BACKGROUND: Globalization has facilitated the employability of doctors almost
anywhere in the world. In recent years, the migration of doctors seems to have
increased. However, we lack studies on doctors' migration from developed
countries. Because the economic recession experienced by many countries might
have affected the migration of doctors, research on this topic is important for
the retention of doctors. Iceland was hit hard by the economic recession in 2008.
Therefore, we want to explore how many specialist doctors in Iceland have
considered migrating and whether economic factors at work and in private life,
such as extensive cost-containment initiatives at work and worries about personal
finances, are related to doctors' migration considerations. METHODS: In 2010, all
doctors in Iceland registered with the Icelandic Medical Association were sent an
electronic cross-sectional survey by email. The 467 specialists who participated
in this study represent 55% of all specialist doctors working in Iceland.
Information on doctors' contemplation of migration was available from responses
to the question: "Have you considered moving and working abroad?" The predictor
variables in our logistic regression model are perceived cost-containment
initiatives at work, stress related to personal finances, experience of working
abroad during vacations, job dissatisfaction, job position, age, and gender.
RESULTS: Sixty-three per cent of Iceland's specialist doctors had considered
relocation abroad, 4% were moving in the next year or two, and 33% had not
considered relocating. Logistic regression analysis shows that, controlling for
age, gender, job position, job satisfaction, and experience of working abroad
during vacations, doctors' migration considerations were significantly affected
by their experiences of cost-containment initiatives at work (odds ratio (OR) =
2.0, p < 0.01) and being stressed about personal finances (OR = 1.6, p < 0.001).
Age, job satisfaction, and working abroad during vacations also had an effect,
whereas job position did not. CONCLUSIONS: Economic factors affect whether
specialist doctors in Iceland consider migration. More studies on the effect of
economic recession on migration by doctors are needed.
PMID- 24350578
TI - The eye-tracking computer device for communication in amyotrophic lateral
sclerosis.
AB - OBJECTIVE: To explore the effectiveness of communication and the variables
affecting the eye-tracking computer system (ETCS) utilization in patients with
late-stage amyotrophic lateral sclerosis (ALS). METHODS: We performed a telephone
survey on 30 patients with advanced non-demented ALS that were provisioned an
ECTS device. Median age at interview was 55 years (IQR = 48-62), with a
relatively high education (13 years, IQR = 8-13). A one-off interview was made
and answers were later provided with the help of the caregiver. The interview
included items about demographic and clinical variables affecting the daily ETCS
utilization. RESULTS: The median time of ETCS device possession was 15 months
(IQR = 9-20). The actual daily utilization was 300 min (IQR = 100-720), mainly
for the communication with relatives/caregiver, internet surfing, e-mailing, and
social networking. 23.3% of patients with ALS (n = 7) had a low daily ETCS
utilization; most reported causes were eye-gaze tiredness and oculomotor
dysfunction. CONCLUSIONS: Eye-tracking computer system is a valuable device for
AAC in patients with ALS, and it can be operated with a good performance. The
development of oculomotor impairment may limit its functional use.
PMID- 24350579
TI - Is adjuvant radiotherapy warranted in resected pT1-2 node-positive rectal cancer?
AB - BACKGROUND: Stage T1-2 rectal cancers are unlikely to have lymph node metastases
and neoadjuvant therapy is not routinely administered. Postoperative management
is controversial if lymph node metastases are detected in the resected specimen.
We studied the outcomes of patients with pT1-2 node-positive rectal cancer in
order to determine whether adjuvant radiotherapy was beneficial. METHODS: We
conducted a retrospective analysis of 284 patients with pathological T1-2 node
positive rectal cancer from a single institution. Outcomes, including local
recurrence (LR), distant metastasis (DM), disease free survival (DFS) and overall
survival (OS), were studied in patients with detailed TN staging and different
adjuvant treatment modalities. RESULTS: The overall 5-year LR, DM, DFS and OS
rates for all patients were 12.5%, 32.9%, 36.4% and 76.8%, respectively. Local
control was inferior among patients who received no adjuvant therapy. Patients
could be divided into three risk subsets: Low-risk, T1N1; Intermediate-risk, T2N1
and T1N2; and High-risk, T2N2. The 5-year LR rates were 5.3%, 9.8% and 26.4%,
respectively (p = 0.005). In High-risk patients, addition of radiotherapy
achieved a 5-year LR rate of 9.1%, compared 34.8% without radiotherapy.
CONCLUSIONS: In our study, we provide the detailed outcomes and preliminary
survival analysis in a relatively infrequent subset of rectal cancer. Three risk
subsets could be identified based on local control for pT1-2 node positive rectal
cancer. Postoperative treatment needs to be individualized for patients with pT1
2 node-positive rectal cancer.
PMID- 24350580
TI - Sequencing error correction without a reference genome.
AB - BACKGROUND: Next (second) generation sequencing is an increasingly important tool
for many areas of molecular biology, however, care must be taken when
interpreting its output. Even a low error rate can cause a large number of errors
due to the high number of nucleotides being sequenced. Identifying sequencing
errors from true biological variants is a challenging task. For organisms without
a reference genome this difficulty is even more challenging. RESULTS: We have
developed a method for the correction of sequencing errors in data from the
Illumina Solexa sequencing platforms. It does not require a reference genome and
is of relevance for microRNA studies, unsequenced genomes, variant detection in
ultra-deep sequencing and even for RNA-Seq studies of organisms with sequenced
genomes where RNA editing is being considered. CONCLUSIONS: The derived error
model is novel in that it allows different error probabilities for each position
along the read, in conjunction with different error rates depending on the
particular nucleotides involved in the substitution, and does not force these
effects to behave in a multiplicative manner. The model provides error rates
which capture the complex effects and interactions of the three main known causes
of sequencing error associated with the Illumina platforms.
PMID- 24350581
TI - Circular permutation of a WW domain: folding still occurs after excising the turn
of the folding-nucleating hairpin.
AB - A hyperstable Pin1 WW domain has been circularly permuted via excision of the
fold-nucleating turn; it still folds to form the native three-strand sheet and
hydrophobic core features. Multiprobe folding dynamics studies of the normal and
circularly permuted sequences, as well as their constituent hairpin fragments and
comparable-length beta-strand-loop-beta-strand models, indicate 2-state folding
for all topologies. N-terminal hairpin formation is the fold nucleating event for
the wild-type sequence; the slower folding circular permutant has a more
distributed folding transition state.
PMID- 24350583
TI - Does enhancement of oxidative stress markers mediate health effects of ambient
air particles?
AB - Evidence indicates that oxidative stress generation may contribute to health
effects associated with particulate matter (PM) exposure. We investigated
oxidative stress markers in 113 workers exposed to metal-rich PM and 61
nonexposed comparable volunteers. The plasma levels of soluble NOX2-derived
peptide (sNOX2-dp) and two oxidative stress markers, urinary 8
hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandinF2alpha (8-iso-PGF2alpha),
were analyzed. The plasma levels of the antioxidant alpha-tocopherol were also
evaluated. The workers' average exposure to PM with an aerodynamic diameter <10
MUm (PM10) was much higher at the workplace than in the city, where the
volunteers lived. Workers had significantly higher urinary 8-iso-PGF2alpha and 8
OHdG and plasma sNOX2-dp levels than nonexposed subjects. Alpha-tocopherol was
much lower in workers compared with nonexposed subjects. In multivariable
regression models adjusted for age, body mass index, and smoking, 8-iso-PGF2alpha
increased in workers in association with PM10 and metal exposure; 8-OHdG and
sNOX2-dp were associated only with iron. Alpha-tocopherol was inversely
associated with each of the oxidative stress markers. Our observation leads to
the hypothesis that the enhancement of oxidative stress markers associated with
exposure to high metal-rich PM levels represents a possible step in the pathways
leading from particle exposure to systemic (e.g., cardiovascular) effects.
PMID- 24350582
TI - Improvement in rheumatic fever and rheumatic heart disease management and
prevention using a health centre-based continuous quality improvement approach.
AB - BACKGROUND: Rheumatic heart disease (RHD) remains a major health concern for
Aboriginal Australians. A key component of RHD control is prevention of recurrent
acute rheumatic fever (ARF) using long-term secondary prophylaxis with
intramuscular benzathine penicillin (BPG). This is the most important and cost
effective step in RHD control. However, there are significant challenges to
effective implementation of secondary prophylaxis programs. This project aimed to
increase understanding and improve quality of RHD care through development and
implementation of a continuous quality improvement (CQI) strategy. METHODS: We
used a CQI strategy to promote implementation of national best-practice ARF/RHD
management guidelines at primary health care level in Indigenous communities of
the Northern Territory (NT), Australia, 2008-2010. Participatory action research
methods were employed to identify system barriers to delivery of high quality
care. This entailed facilitated discussion with primary care staff aided by a
system assessment tool (SAT). Participants were encouraged to develop and
implement strategies to overcome identified barriers, including better record
keeping, triage systems and strategies for patient follow-up. To assess
performance, clinical records were audited at baseline, then annually for two
years. Key performance indicators included proportion of people receiving
adequate secondary prophylaxis (>=80% of scheduled 4-weekly penicillin
injections) and quality of documentation. RESULTS: Six health centres
participated, servicing approximately 154 people with ARF/RHD. Improvements
occurred in indicators of service delivery including proportion of people
receiving >=40% of their scheduled BPG (increasing from 81/116 [70%] at baseline
to 84/103 [82%] in year three, p = 0.04), proportion of people reviewed by a
doctor within the past two years (112/154 [73%] and 134/156 [86%], p = 0.003),
and proportion of people who received influenza vaccination (57/154 [37%] to
86/156 [55%], p = 0.001). However, the proportion receiving >=80% of scheduled
BPG did not change. Documentation in medical files improved: ARF episode
documentation increased from 31/55 (56%) to 50/62 (81%) (p = 0.004), and RHD risk
category documentation from 87/154 (56%) to 103/145 (76%) (p < 0.001). Large
differences in performance were noted between health centres, reflected to some
extent in SAT scores. CONCLUSIONS: A CQI process using a systems approach and
participatory action research methodology can significantly improve delivery of
ARF/RHD care.
PMID- 24350586
TI - Evaluation of two modified culture media for Leishmania infantum cultivation
versus different culture media.
AB - The aim of this study is to improve the cultivation of Leishmania promastigotes
without the use of common, semisolid culture media such as Evans' modified
Tobie's medium (EMTM), liquid RPMI 1640, and Peptone-yeast extract medium (P-Y).
Although EMTM medium permits the growth of a high number of parasites, it is
technically difficult to prepare as it requires the use of fresh rabbit blood
from animals bred on farms, while RPMI 1640 and P-Y show lower growth rates than
the EMTM. There is, therefore, a need to develop new blood-free and time-saving
culture systems. The aim of this paper is to propose new modified microbiological
media, named RPMI-PY and Tobie-PY, to isolate Leishmania and cultivate parasites
for research and diagnostic purposes. This study compares classic culture media
to the new media, RPMI-PY and Tobie-PY, and demonstrates that the new media have
superior performance in terms of time and parasitic load. The growth rate of the
parasite was significantly higher at 24, 48, and 72 hr cultivation, based on
counts using Burker's chambers, when compared to classic media. This study was
carried out at the National References Centre for Leishmaniasis (C.Re.Na.L.)
where the isolation procedures are conducted daily from a number of different
biological matrices.
PMID- 24350587
TI - Streptococcus pneumoniae serotype distribution in children in the Russian
Federation before the introduction of pneumococcal conjugate vaccines into the
National Immunization Program.
AB - WHO recommends the inclusion of PCVs in childhood vaccination programs world
wide. Many countries including the Russian Federation are currently planning the
inclusion of PCVs in their National Immunization Programs and, therefore, data on
the pneumococcal serotype distribution is important to estimate the potential
disease impact. Here we review eight recent epidemiological studies on the
pneumococcal serotype distribution from Russia. Across all studies, serotypes 6B,
14, 19F and 23F were the most prevalent. Interestingly, serotype 3 was relatively
common. Serotype 19A was prevalent among AOM, CAP and nasopharyngeal isolates and
among antibiotic resistant isolates in all age groups. The differences in
serotype coverage between PCV10 and PCV13 were up to 26%. Based on the current
data on serotype distribution, a wide use of PCVs in Russia may lead to a
significant reduction of the pneumococcal disease burden.
PMID- 24350588
TI - In depth analysis of the quenching of three fluorene-phenylene-based cationic
conjugated polyelectrolytes by DNA and DNA bases.
AB - The interaction of three cationic poly {9,9-bis[N,N
(trimethylammonium)hexyl]fluorene-co-1,4-phenylene} polymers with average chain
lengths of ~6, 12, and 100 repeat units (PFP-NR36(I),12(Br),100(Br)) with both
double and single stranded, short and long, DNA and DNA bases have been studied
by steady state and time-resolved fluorescence techniques. Fluorescence of PFP
NR3 polymers is quenched with high efficiency by DNA (both double and single
stranded) and DNA bases. The resulting quenching plots are sigmoidal and are not
accurately described by using a Stern-Volmer quenching mechanism. Here, the
quenching mechanism is well modeled in terms of an equilibrium in which a PFP
NR3/DNA aggregate complex is formed which brings polymer chains into close enough
proximity to allow interchain excitation energy migration and quenching at
aggregate or DNA base traps. Such an analysis gives equilibrium constants of 8.4
* 10(6) (+/-1.2 * 10(6)) M(-1) for short-dsDNA and 8.6 * 10(6) (+/-1.7 * 10(6))
M(-1) for short-ssDNA with PFP-NR36(I).
PMID- 24350589
TI - Age at menarche and risky sexual partnerships in adulthood: does a biosocial
model explain any associations?
AB - BACKGROUND: The purpose of this study was to examine the association between
menarcheal age and subsequent sexual partnering in women aged 21-44 years.
METHODS: Data from the 2006-2010 National Survey of Family Growth were used
(n=7,962). Menarcheal age was defined as <= 11, 12-14, or >= 15 years. Sexual
partnering was defined as being concurrent, serially monogamous or monogamous in
the previous year. Polytomous logistic regression models evaluated the
association between age of menarche and sexual partnering. RESULTS: Nearly 6%
reported concurrent partnerships and ~ 4% serial monogamy. Age of menarche was
not associated with subsequent concurrent sexual partnering (adjusted odds ratio
relative to >= 18 years [aOR <= 11]: 1.09; 95% confidence interval [CI]: 0.57
2.09; aOR12-14: 1.13; 95% CI: 0.64-1.99) or serial monogamy (aOR <= 11: 0.75; 95%
CI: 0.41-1.38; aOR12-14: 0.71; 95% CI: 0.39-1.29). CONCLUSIONS: Early menarche is
not a risk factor for sexual partnering in adulthood. However, menarche provides
an opportunity for education to aid young women to make decisions regarding
sexual debut and sexual partnering that are healthy for them.
PMID- 24350591
TI - Assessment of sex differences in plaque morphology by coronary computed
tomography angiography--are men and women the same?
AB - PURPOSE: The objective of this study was to assess whether sex differences exist
in plaque burden and plaque subtype as assessed by coronary computed tomography
angiography (CCTA). METHODS: The study cohort included 937 consecutive patients
who underwent CCTA between 2008 and 2010. Stenosis was quantified using the
Society of Cardiovascular Computed Tomography stenosis grading scale and a total
stenosis score (TSS) was generated. Plaque morphology (PM) was reported as
predominantly calcified (CP), noncalcified (NCP), or mixed (MP) plaque, and CP,
NCP, and MP percentages were calculated. RESULTS: On multivariate analysis, men
were significantly more likely to have plaque (65.9% of men vs. 44.6% of women,
p<0.001), at least one segment with >=50% stenosis (22.7% of men vs. 10.3% of
women, p<0.001) and higher TSS (mean score=2.81 for men vs. 1.58 for women,
p<0.001). Sex was the strongest predictor in all models (odds ratio [OR]=2.55,
95% confidence interval [CI] 1.78-3.67, p<0.001 for any plaque; OR=2.48, 95% CI
1.48-4.16, p<0.01 for segments with >=50% stenosis; beta=1.46, 95% CI 0.69-2.22,
p<0.001 for TSS). Among patients with coronary plaque present, no significant sex
differences in PM were found. CONCLUSIONS: Sex was the strongest risk factor for
the presence and extent of plaque. Significant sex differences in PM did not
exist.
PMID- 24350590
TI - Socioeconomic disparities in breast cancer treatment among older women.
AB - BACKGROUND: Racial disparities in breast cancer treatment among Medicare
beneficiaries have been documented. This study aimed to determine whether racial
disparities exist among white and black female Medicare beneficiaries in Alabama,
an economically disadvantaged U.S. state. METHODS: From a linked dataset of
breast cancer cases from the Alabama Statewide Cancer Registry and fee-for
service claims from Medicare, we identified 2,097 white and black females, aged
66 years and older, who were diagnosed with stages 1-3 breast cancer from January
1, 2000, to December 31, 2002. Generalized estimating equation (GEE) models were
used to determine whether there were racial differences in initiating and
completing National Comprehensive Cancer Network Clinical Practice guideline
specific treatment. RESULTS: Sixty-two percent of whites and 64.7% of blacks had
mastectomy (p=0.27); 34.6% of whites and 30.2% of blacks had breast conserving
surgery (BCS) (p=0.12). Among those who had BCS, 76.8% of whites and 83.3% of
blacks started adjuvant radiation therapy (p=0.33) and they equally completed
adjuvant radiation therapy (p=0.29). For women with tumors over 1 centimeter,
whites and blacks were equally likely to start (16.1% of whites and 18.3% of
black; p=0.34) and complete (50.6% of whites and 46.3% of black; p=0.87) adjuvant
chemotherapy. There were still no differences after adjusting for confounders
using GEE. However, differences were observed by area-level socioeconomic status
(SES), with lower SES residents more likely to receive a mastectomy (odds ratio
[OR]=1.26; 95% confidence interval [CI]: 1.01-1.57) and initiate radiation after
BCS (OR=2.24; 95% CI: 1.28-3.93). CONCLUSIONS: No racial differences were found
in guideline-specific breast cancer treatment or treatment completion, but there
were differences by SES. Future studies should explore reasons for SES
differences and whether similar results hold in other economically disadvantaged
U.S. states.
PMID- 24350592
TI - Syntheses, crystal structures, and magnetic properties of four new cyano-bridged
bimetallic complexes based on the mer-[Fe(III)(qcq)(CN)3]- building block.
AB - Four new cyano-bridged bimetallic complexes,
[{Mn(III)(salen)}2{Fe(III)(qcq)(CN)3}2]n.3nCH3CN.nH2O (1) [salen = N,N'
ethylenebis(salicylideneiminato) dianion; qcq(-) = 8-(2-quinoline-2
carboxamido)quinoline anion], [{Mn(III)(salpn)}2{Fe(III)(qcq)(CN)3}2]n.4nH2O (2)
[salpn = N,N'-1,2-propylenebis(salicylideneiminato)dianion],
[{Mn(II)(bipy)(CH3OH)}{Fe(III)(qcq)(CN)3}2]2.2H2O.2CH3OH (3) (bipy = 2,2'
bipyridine), and [{Mn(II)(phen)2}{Fe(III)(qcq)(CN)3}2].CH3CN.2H2O (4) (phen =
1,10-phenanthroline) have been synthesized and characterized both structurally
and magnetically. The structures of 1 and 2 are both unique 1-D linear branch
chains with additional structural units of
{Mn(III)(salen/salpn)}{Fe(III)(qcq)(CN)3} dangling on the sides. In contrast, 3
and 4 are cyano-bridged bimetallic hexanuclear and trinuclear clusters,
respectively. The intermolecular short contacts such as pi-pi interactions and
hydrogen bonds extend 1-4 into high dimensional supermolecular networks. Magnetic
investigation reveals the dominant intramolecular antiferromagnetic interactions
in 1, 3, and 4, while ferromagnetic and antiferromagnetic interactions coexist in
2. Alternating current measurement at low temperature indicates the existence of
slow magnetic relaxation in 1 and 2, which should be due to the single ion
anisotropy of Mn(III).
PMID- 24350593
TI - Suicidal behavior and attitudes in Slovak and Turkish high school students: a
cross-cultural investigation.
AB - Suicidal behavior and its variation across social contexts are of importance for
the science of suicidology. Due to its special character controlled experimental
studies on suicide are ruled out for ethical reasons. Cross-cultural studies may
throw light on the etiology of both suicidal behavior and its cross-cultural
variation. The present study compared suicidal behavior and attitudes in 423
Slovak and 541 Turkish high school students by means of a self-report
questionnaire. The two groups reported similar percentages (Slovak = 36.4%;
Turkish = 33.8%) of lifetime, past 12-months or current suicidal ideation but
significantly more Turkish (12.2%) than Slovak (4.8%) students reported lifetime
or past 12-months suicide attempts. Slovak adolescents displayed more liberal and
permissive attitudes toward suicide, while those of Turkish adolescents were more
rejecting. Turkish students rated themselves to be more religious and hence they
believed to a greater extent that suicidal persons would be punished in a life
after death than their Slovak peers. However, attitudes of Turkish students
toward an imagined suicidal close friend were more accepting than the attitudes
of Slovak students. Comparison of suicidal and nonsuicidal students revealed that
those reporting suicidal ideation or attempts were more accepting of suicide and
viewed suicide as a solution to a greater extent than the nonsuicidal ones. The
results from this study suggest that cultural factors play a role in suicidal
behavior, attitudes and reactions in a predicted direction.
PMID- 24350594
TI - Plasticity of in vitro-generated urothelial cells for functional tissue
formation.
AB - Tissue-engineering and regenerative medicine strategies for the bladder and
urinary tract are dependent on the ability to generate adequate numbers of
differentiation-competent uro-epithelial cells. In situ, urothelium is a
mitotically quiescent, but highly regenerative epithelium. Although evidence
supports a resident, basally located urothelial progenitor population, no
specific stem cell has been identified. Our aim was to isolate basal and
suprabasal urothelial subpopulations and characterize their regenerative and
differentiation potentials in vitro. We showed that the low-affinity nerve growth
factor receptor (NGFR) is a cell surface-expressed marker that is restricted to
basal cells in normal human and porcine urothelia in situ. We used NGFR
immunoseparation and differential adherence to collagen to isolate subpopulations
of urothelial cells for culture. Isolated basal-derived porcine NGFR+ urothelial
cells initially showed a higher proliferative and clonogenic phenotype than their
suprabasal NGFR- counterparts in vitro. However, after a short period of
adaptation to culture, both NGFR+ and NGFR- subpopulations became
indistinguishable and displayed similar long-term growth and differentiation
potentials. Both populations generated hierarchically organized, differentiated
tissue equivalents similar to native urothelium, including a fully reconstituted
NGFR+ basal cell layer by the NGFR- suprabasal-derived population. Similarly,
slow collagen-adherent human urothelial cells initially displayed a longer lag
phase than rapid-adherent cultures, but after adaptation, both populations showed
similar long-term proliferation, exponential growth rates, and capacity to form a
functional barrier urothelium. Our results support a model where urothelial cell
phenotype is plastic and determined by the niche or local environment. This has
direct implications for tissue-engineering strategies requiring urothelial cell
expansion and provides a new perspective toward understanding urothelial
regeneration and differentiated tissue hierarchy.
PMID- 24350595
TI - Facile synthesis of acridine derivatives by ZnCl2-promoted intramolecular
cyclization of o-arylaminophenyl Schiff bases.
AB - A concise and efficient method for the synthesis of a wide range of acridine
derivatives and polycyclic aza-aromatic compounds from a ZnCl2-promoted
cyclization reaction of readily available o-arylaminophenyl Schiff base compounds
under convenient conditions was developed. Reaction conditions and scope of the
new method were examined in detail.
PMID- 24350596
TI - Cascaded assembly of complex multiparticle patterns.
AB - A method for the cascaded capillary assembly of different particle populations in
a single assembly cycle is presented. The method addresses the increasing need
for fast and simple fabrication of multicomponent arrays from colloidal micro-
and nanoscale building blocks for constructing nanoelectronic, optical, and
sensing devices. It is based on the use of a microfluidic device from which two
independent capillary bridges extend. The menisci of the capillary bridges are
pulled over a template with trapping sites that receive the colloidal particles.
We describe the parameters for simultaneous, high-yield assembly from both
menisci and demonstrate the applicability of the process by means of the size
selective assembly of particles of different diameters and also by the
fabrication of two-component particle clusters with defined shape and
composition. This approach allows the fabrication of multifunctional particle
clusters having different functionalities at predetermined positions.
PMID- 24350597
TI - Changes in peak fat oxidation in response to different doses of endurance
training.
AB - The effect of different doses of endurance training on the capacity to oxidize
fat during exercise in sedentary, overweight men and assessment of variables
associated with changes in peak fat oxidation (PFO) were evaluated. Young,
sedentary, overweight men were randomized to either the high-dose (HIGH, 600
kcal/day, n = 17) or moderate-dose (MOD, 300 kcal/day, n = 18) endurance training
groups or controls (CON, n = 15). PFO and peak oxygen uptake (VO2 peak) were
measured using indirect calorimetry, body composition using dual-energy x-ray
absorptiometry, and protein levels of mitochondrial enzymes determined by Western
blotting. PFO increased in both MOD [1.2 mg/kg fat-free mass (FFM)/min, 95%
confidence interval (CI): 0.08:2.3, P = 0.03] and HIGH (1.8 mg/kg FFM/min, CI:
0.6:2.9, P < 0.001) compared with CON. Skeletal muscle expression of citrate
synthase, beta-hydroxyacyl-CoA dehydrogenase, and mitochondrial oxphos complexes
II-V increased similarly in MOD and HIGH. Stepwise multiple linear regression
analysis with backward elimination of individual variables correlated with
changes in PFO revealed increases in cycling efficiency, FFM, and VO2 peak as the
remaining associated variables. In conclusion, PFO during exercise increased with
both moderate- and high-dose endurance training. Increases in PFO were mainly
predicted by changes in VO2 peak, FFM, and cycling efficiency, and less with
skeletal muscle mitochondrial enzymes.
PMID- 24350598
TI - Nonscalable oxidation catalysis of gold clusters.
AB - Small, negatively charged gold clusters isolated in vacuum can oxidize CO via
electron-transfer-mediated activation of O2. This suggests that Au clusters can
act as aerobic oxidation catalysts in the real world when their structure
parameters satisfy given required conditions. However, there is a technical
challenge for the development of Au cluster oxidation catalysts; the structural
parameters of the Au clusters, such as size and composition, must be precisely
controlled because the intrinsic chemical properties of the clusters are strongly
dependent on these parameters. This Account describes our efforts to achieve
precision synthesis of small (diameter <2 nm) Au clusters, stabilized by polymers
and immobilized on supports, for a variety of catalytic applications. Since we
aim to develop Au cluster catalysts by taking full advantage of their intrinsic,
size-specific chemical nature, we chose chemically inert materials for the
stabilizers and supports. We began by preparing small Au clusters weakly
stabilized by polyvinylpyrrolidone (PVP) to test the hypothesis that small Au
clusters in the real world will also show size-specific oxidation catalysis. The
size of Au:PVP was controlled using a microfluidic device and monitored by mass
spectrometry. We found that only Au clusters smaller than a certain critical size
show a variety of aerobic oxidation reactions and proposed that the reactions
proceed via catalytic activation of O2 by negatively charged Au clusters. We also
developed a method to precisely control the size and composition of supported Au
clusters using ligand-protected Au and Au-based bimetallic clusters as
precursors. These small Au clusters immobilized on mesoporous silica,
hydroxyapatite, and carbon nanotubes acted as oxidation catalysts. We have
demonstrated for the first time an optimal Au cluster size for the oxidation of
cyclohexane and a remarkable improvement in the oxidation catalysis of Au25
clusters by single-atom Pd doping. The non-scalable catalysis of Au clusters that
we reported here points to the possibility that novel catalysis beyond that
expected from bulk counterparts can be developed simply by reducing the catalyst
size to the sub-2 nm regime.
PMID- 24350599
TI - Variation in the coding and 3' untranslated regions of the porcine prolactin
receptor short form modifies protein expression and function.
AB - The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms
(SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional
analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms
(SNPs) within exon 11 of the pPRLR-SF give rise to four amino acid haplotypes of
the intracellular domain. We identified the dimorphic insertion of a short
interspersed repetitive DNA element (PRE-1) along with 32 SNPs and four other
insertion/deletion sites within the 3' untranslated region (UTR) of pPRLR-SF. The
PRE-1 element reduced protein translation in vitro by 75%, whereas the
combination of 10 SNPs and one insertion/deletion decreased translation by 50%.
Full-length cDNAs for all four haplotypes of pPRLR-SF were cloned behind the
elongation factor 1-alpha promoter and functionally analyzed in vitro. None of
the haplotypes could initiate transcription from the beta-casein promoter,
whereas all four were dominant negatives against PRL-activation of the pPRLR-LF.
Two of the haplotypes completely inhibited pPRLR-LF activity at a four-fold
excess, whereas the others required a six-fold excess to impart the same effect.
The ligand binding affinities of the pPRLR-SF haplotypes did not differ.
Expression of the pPRLR-SF increased linearly during gestation in the endometrium
and was hormonally regulated in a tissue-specific manner in the mammary glands
and uterus. In conclusion, we identified a PRE-1 and other SNPs in the pPRLR-SF
3' UTR that reduce protein expression and four haplotypes of the pPRLR-SF that
suppress pPRLR-LF signaling and may differentially impact the phenotypic effects
of PRL in vivo.
PMID- 24350600
TI - Sexual hookups and adverse health outcomes: a longitudinal study of first-year
college women.
AB - "Hookups" are sexual encounters between partners who are not in a romantic
relationship and do not expect commitment. We examined the associations between
sexual hookup behavior and depression, sexual victimization (SV), and sexually
transmitted infections (STIs) among first-year college women. In this
longitudinal study, 483 women completed 13 monthly surveys assessing oral and
vaginal sex with hookup and romantic partners, depression, SV, and self-reported
STIs. Participants also provided biological specimens that were tested for STIs.
During the study, 50% of participants reported hookup sex and 62% reported
romantic sex. Covariates included previous levels of the outcome, alcohol use,
impulsivity, sensation seeking, and romantic sex. Autoregressive cross-lagged
models showed that, controlling for covariates, hookup behavior during college
was correlated with depression, Bs = .21, ps < .05, and SV, Bs = .19, ps < .05.
In addition, precollege hookup behavior predicted SV early in college, B = .62, p
< .05. Hookup sex, OR 1.32, p < .05, and romantic sex, OR 1.19, p < .05, were
associated with STIs. Overall, sexual hookup behavior among college women was
positively correlated with experiencing depression, SV, and STIs, but the nature
of these associations remains unclear, and hooking up did not predict future
depression.
PMID- 24350602
TI - Recommendations abstracted from the American Geriatrics Society Consensus
Statement on vitamin D for Prevention of Falls and Their Consequences.
AB - The goal of this Consensus Statement is to help primary care practitioners
achieve adequate vitamin D intake from all sources in their older patients, with
the goal of reducing falls and fall-related injuries. The workgroup graded the
quality of evidence and assigned an evidence level using established criteria.
Based on the evidence for fall and fracture reduction in the clinical trials of
older community-dwelling and institutionalized persons and metaanalyses, the
workgroup concluded that a serum 25 hydroxyvitamin D (25(OH)D) concentration of
30 ng/mL (75 nmol/L) should be a minimum goal to achieve in older adults,
particularly in frail adults, who are at higher risk of falls, injuries, and
fractures. The workgroup concluded that the goal--to reduce fall injuries related
to low vitamin D status--could be achieved safely and would not require
practitioners to measure serum 25(OH)D concentrations in older adults in the
absence of underlying conditions that increase the risk of hypercalcemia (e.g.,
advanced renal disease, certain malignancies, sarcoidosis).
PMID- 24350601
TI - Probabilistic grammatical model for helix-helix contact site classification.
AB - BACKGROUND: Hidden Markov Models power many state-of-the-art tools in the field
of protein bioinformatics. While excelling in their tasks, these methods of
protein analysis do not convey directly information on medium- and long-range
residue-residue interactions. This requires an expressive power of at least
context-free grammars. However, application of more powerful grammar formalisms
to protein analysis has been surprisingly limited. RESULTS: In this work, we
present a probabilistic grammatical framework for problem-specific protein
languages and apply it to classification of transmembrane helix-helix pairs
configurations. The core of the model consists of a probabilistic context-free
grammar, automatically inferred by a genetic algorithm from only a generic set of
expert-based rules and positive training samples. The model was applied to
produce sequence based descriptors of four classes of transmembrane helix-helix
contact site configurations. The highest performance of the classifiers reached
AUCROC of 0.70. The analysis of grammar parse trees revealed the ability of
representing structural features of helix-helix contact sites. CONCLUSIONS: We
demonstrated that our probabilistic context-free framework for analysis of
protein sequences outperforms the state of the art in the task of helix-helix
contact site classification. However, this is achieved without necessarily
requiring modeling long range dependencies between interacting residues. A
significant feature of our approach is that grammar rules and parse trees are
human-readable. Thus they could provide biologically meaningful information for
molecular biologists.
PMID- 24350604
TI - Oases to oblivion: the rapid demise of springs in the South-eastern Great
Artesian Basin, Australia.
PMID- 24350603
TI - Structural proteins from whelk egg capsule with long range elasticity associated
with a solid-state phase transition.
AB - The robust, proteinaceous egg capsules of marine prosobranch gastropods (genus
Busycotypus ) exhibit unique biomechanical properties such as high elastic strain
recovery and elastic energy dissipation capability. Capsule material possesses
long-range extensibility that is fully recoverable and is the result of a
secondary structure phase transition from alpha-helical coiled-coil to extended
beta-sheet rather than of entropic (rubber) elasticity. We report here the
characterization of the precursor proteins that make up this material. Three
different proteins have been purified and analyzed, and complete protein
sequences deduced from messenger ribonucleic acid (mRNA) transcripts. Circular
dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy indicate that
the proteins are strongly alpha-helical in solution and primary sequence analysis
suggests that these proteins have a propensity to form coiled-coils. This is in
agreement with previous wide-angle X-ray scattering (WAXS) and solid-state Raman
spectroscopic analysis of mature egg capsules.
PMID- 24350605
TI - Role of gap junctions modulating hepatic vascular tone in cirrhosis.
AB - BACKGROUND & AIMS: Gap junctions are formed by connexins (Cx), a family of
proteins that couple endothelial and smooth muscle cells in systemic vessels. In
this context, Cx allow the transmission of signals modulating vascular tone.
Recently, vascular Cx have been observed in liver cells implicated in liver blood
flow regulation. Here, we investigated the role of Cx in the regulation of
intrahepatic vascular tone in cirrhosis. METHODS: Livers of Sprague-Dawley
control and cirrhotic (common bile duct ligation-CBDL and CCl4 ) rats were
perfused, and concentration-effect curves in response to acetylcholine (ACh)
precontracted with methoxamine were obtained in the presence of the specific Cx
inhibitor 18-alpha-glycyrrhetinic acid or vehicle. Cx expression was assessed by
immunofluorescence, western blot and reverse-transcription polymerase chain
reaction in liver tissue, hepatic stellate cells, sinusoidal endothelial cells
and hepatocytes isolated from control and cirrhotic rat livers. Cx protein
expression was also determined in cirrhotic human tissue. RESULTS: Gap junction
blockade markedly attenuated relaxation of hepatic vasculature in response to ACh
in control (maximal relaxation, -55 +/- 10.5% vs. -95.3 +/- 10% with vehicle; P <
0.01) and CBDL rats (50.9 +/- 18.5% vs. -18.7 +/- 5.5% with vehicle; P = 0.01).
Livers from CBDL rats and patients with cirrhosis exhibited Cx overexpression. By
contrast, CCl4 -cirrhotic rats did not show attenuated relaxation of hepatic
vasculature after blockade and Cx expression was significantly lower than in
controls. CONCLUSIONS: Gap junctions may contribute to modulating portal pressure
and intrahepatic vascular relaxation. Liver gap junctions may represent a new
therapeutic target in cirrhotic portal hypertension.
PMID- 24350606
TI - Functional link between Rab GTPase-mediated membrane trafficking and PI4,5P2
signaling.
AB - Fission yeast its3(+) encodes an essential phosphatidylinositol-4-phosphate 5
kinase (PI4P5K) that regulates cell integrity and cytokinesis. We performed a
genetic screen to identify genes that function in PI4P5K-mediated signaling, and
identified gyp10(+) encoding a Rab GTPase-activating protein (GAP), a negative
regulator for Rab GTPase signaling. Its3 overproduction caused growth defects and
abnormal cytoplasmic accumulation of the Its3 protein, which can be stained by
calcofluor. Notably, Its3 overproducing cells displayed abnormal membranous
structures, multilamella Golgi and fragmented vacuoles showed by Electron
microscopy. Furthermore, the excess cytoplasmic Its3 structure partly colocalized
with the fluorescence of FM4-64. Gyp10 rescued both growth defects and abnormal
Its3 localization when it was over-expressed. Gyp10 functionally interacted with
the Rab GTPases Ypt3 and Ryh1, both of which regulate Golgi membrane trafficking.
Consistently, mutation or deletion of Ypt3 and Ryh1 suppressed phenotypes
associated with Its3 overproduction. Importantly, the plasma membrane
localization of Its3 was also affected by the impairment of the Ypt3/Ryh1 Rab
membrane trafficking, thus suggesting that membrane trafficking events regulated
by two Rab GTPases functionally interacts with PI4,5P2 signaling. These results
suggest a mechanism whereby PI4P5K signaling/localization is affected by Golgi
membrane trafficking, thus provide a functional link between the PI4,5P2
signaling and Rab-mediated trafficking.
PMID- 24350607
TI - Determinants of regioselective hydroxylation in the fungal polysaccharide
monooxygenases.
AB - The ubiquitous fungal polysaccharide monooxygenases (PMOs) (also known as GH61
proteins, LPMOs, and AA9 proteins) are structurally related but have significant
variation in sequence. A heterologous expression method in Neurospora crassa was
developed as a step toward connecting regioselectivity of the chemistry to PMO
phylogeny. Activity assays, as well as sequence and phylogenetic analyses, showed
that the majority of fungal PMOs fall into three major groups with distinctive
active site surface features. PMO1s and PMO2s hydroxylate glycosidic positions C1
and C4, respectively. PMO3s hydroxylate both C1 and C4. A subgroup of PMO3s
(PMO3*) hydroxylate C1. Mutagenesis studies showed that an extra subdomain of
about 12 amino acids contribute to C4 oxidation in the PMO3 family.
PMID- 24350608
TI - Rapid genomic and transcriptomic alterations induced by wide hybridization:
Chrysanthemum nankingense * Tanacetum vulgare and C. crassum * Crossostephium
chinense (Asteraceae).
AB - BACKGROUND: Hybridization is a major driver of evolution in plants. In a number
of plant species, the process of hybridization has been revealed to be
accompanied by wide-ranging genetic and epigenetic alterations, some of which
have consequences on gene transcripts. The Asteraceae family includes a number of
polyploid species, and wide crossing is seen as a viable means of genetically
improving ornamental species such as Chrysanthemum spp. However, the consequences
of hybridization in this taxon have yet to be characterized. RESULTS: Amplified
fragment length polymorphism (AFLP), methylation sensitive amplification
polymorphism (MSAP) and cDNA-AFLP profiling of the two intergeneric hybrids C.
nankingense * Tanacetum vulgare and C. crassum * Crossostephium chinense were
employed to characterize, respectively, the genomic, epigenomic and
transcriptomic changes induced by the hybridization event. The hybrids' AFLP
profiles included both the loss of specific parental fragments and the gain of
fragments not present in either parent's profile. About 10% of the paternal
fragments were not inherited by the hybrid, while the corresponding rate for the
maternal parent fragments was around 4-5%. The novel fragments detected may have
arisen either due to heterozygosity in one or other parent, or as a result of a
deletion event following the hybridization. Around one half of the cDNA-AFLP
fragments were common to both parents, about 30% were specific to the female
parent, and somewhat under 20% specific to the male parent; the remainder (2.9
4.7%) of the hybrids' fragments were not present in either parent's profile. The
MSAP fingerprinting demonstrated that the hybridization event also reduced the
amount of global cytosine methylation, since > 50% of the parental fragments were
methylated, while the corresponding frequencies for the two hybrids were 48.5%
and 50.4%. CONCLUSIONS: Combining two different Asteraceae genomes via
hybridization clearly induced a range of genomic and epigenomic alterations, some
of which had an effect on the transcriptome. The rapid genomic and transcriptomic
alterations induced by hybridization may accelerate the evolutionary process
among progenies.
PMID- 24350609
TI - Bacterial profiling of White Plague Disease across corals and oceans indicates a
conserved and distinct disease microbiome.
AB - Coral diseases are characterized by microbial community shifts in coral mucus and
tissue, but causes and consequences of these changes are vaguely understood due
to the complexity and dynamics of coral-associated bacteria. We used 16S rRNA
gene microarrays to assay differences in bacterial assemblages of healthy and
diseased colonies displaying White Plague Disease (WPD) signs from two closely
related Caribbean coral species, Orbicella faveolata and Orbicella franksi.
Analysis of differentially abundant operational taxonomic units (OTUs) revealed
strong differences between healthy and diseased specimens, but not between coral
species. A subsequent comparison to data from two Indo-Pacific coral species
(Pavona duerdeni and Porites lutea) revealed distinct microbial community
patterns associated with ocean basin, coral species and health state. Coral
species were clearly separated by site, but also, the relatedness of the
underlying bacterial community structures resembled the phylogenetic relationship
of the coral hosts. In diseased samples, bacterial richness increased and
putatively opportunistic bacteria were consistently more abundant highlighting
the role of opportunistic conditions in structuring microbial community patterns
during disease. Our comparative analysis shows that it is possible to derive
conserved bacterial footprints of diseased coral holobionts that might help in
identifying key bacterial species related to the underlying etiopathology.
Furthermore, our data demonstrate that similar-appearing disease phenotypes
produce microbial community patterns that are consistent over coral species and
oceans, irrespective of the putative underlying pathogen. Consequently, profiling
coral diseases by microbial community structure over multiple coral species might
allow the development of a comparative disease framework that can inform on cause
and relatedness of coral diseases.
PMID- 24350611
TI - Diffusion of subsidized ACTs in accredited drug shops in Tanzania: determinants
of stocking and characteristics of early and late adopters.
AB - BACKGROUND: Many households in sub-Saharan Africa utilize the private sector as a
primary source of treatment for malaria episodes. Expanding access to effective
treatment in private drug shops may help reduce incidence of severe disease and
mortality. This research leveraged a longitudinal survey of stocking of
subsidized artemisinin combination therapies (ACTs), an effective anti-malarial,
in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This
provided a unique opportunity to explore shop and market level determinants of
product diffusion in a developing country retail market. METHODS: 356 ADDOs in
the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between
Feb 2011 and May 2012. Shop level audits were used to measure the availability of
subsidized ACTs at each shop. Data on market and shop level factors were
collected during the survey and also extracted from GIS layers. Regression and
network based methodologies were used. Shops classified as early and late
adopters, following Rogers' model of product diffusion, were compared. The Bass
model of product diffusion was applied to determine whether shops stocked ACTs
out of a need to imitate market competitors or a desire to satisfy customer
needs. RESULTS: Following the introduction of a subsidy for ACTs, stocking
increased from 12% to nearly 80% over the seven survey rounds. Stocking was
influenced by higher numbers of proximal shops and clinics, larger customer
traffic and the presence of a licensed pharmacist. Early adopters were
characterized by a larger percentage of customers seeking care for malaria, a
larger catchment and sourcing from specific wholesalers/suppliers. The Bass model
of product diffusion indicated that shops were adopting products in response to
competitor behavior, rather than customer demand. CONCLUSIONS: Decisions to stock
new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of
factors related to both market competition and customer demand, but are
particularly influenced by the behavior of competing shops. Efforts to expand
access to new pharmaceutical products in developing country markets could benefit
from initial targeting of high profile shops in competitive markets and wholesale
suppliers to encourage faster product diffusion across all drug retailers.
PMID- 24350612
TI - Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5
fluorouracil: a preliminary study.
AB - Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse
effects and extremely low bioavailability. Therefore, the aim of present
investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU
for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were
prepared by oil phase titration method. Thermodynamically stable nanoemulsions
were characterized in terms of droplet size distribution, zeta potential,
viscosity and refractive index. Selected formulations and control were subjected
to in vitro skin permeation studies through rat skin using Franz diffusion cells.
Optimized formulation F9 was subjected to stability and in vitro cytotoxic
studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in
formulation F9 compared with control and other formulations. The values of steady
state flux and permeability coefficient for formulation F9 were found to be
206.40 +/- 14.56 ug cm(-2) h(-1) and 2.064 * 10(-2) +/- 0.050 * 10(-2 )cm h(-1),
respectively. Optimized formulation F9 was found to be physical stable. In vitro
cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized
nanoemulsion is much more efficacious than free 5-FU. From these results, it can
be concluded that the developed nanoemulsion might be a promising vehicle for
chemoprevention of skin cancer.
PMID- 24350613
TI - Robust anger: recognition of deteriorated dynamic bodily emotion expressions.
AB - In two studies, the robustness of anger recognition of bodily expressions is
tested. In the first study, video recordings of an actor expressing four distinct
emotions (anger, despair, fear, and joy) were structurally manipulated as to
image impairment and body segmentation. The results show that anger recognition
is more robust than other emotions to image impairment and to body segmentation.
Moreover, the study showed that arms expressing anger were more robustly
recognised than arms expressing other emotions. Study 2 added face blurring as a
variable to the bodily expressions and showed that it decreased accurate emotion
recognition-but more for recognition of joy and despair than for anger and fear.
In sum, the paper indicates the robustness of anger recognition in multileveled
deteriorated bodily expressions.
PMID- 24350610
TI - Role of reactive oxygen species in neonatal pulmonary vascular disease.
AB - SIGNIFICANCE: Abnormal lung development in the perinatal period can result in
severe neonatal complications, including persistent pulmonary hypertension (PH)
of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play
a substantive role in the development of PH associated with these diseases. ROS
impair the normal pulmonary artery (PA) relaxation in response to vasodilators,
and ROS are also implicated in pulmonary arterial remodeling, both of which can
increase the severity of PH. RECENT ADVANCES: PA ROS levels are elevated when
endogenous ROS-generating enzymes are activated and/or when endogenous ROS
scavengers are inactivated. Animal models have provided valuable insights into
ROS generators and scavengers that are dysregulated in different forms of
neonatal PH, thus identifying potential therapeutic targets. CRITICAL ISSUES:
General antioxidant therapy has proved ineffective in reversing PH, suggesting
that it is necessary to target specific signaling pathways for successful
therapy. FUTURE DIRECTIONS: Development of novel selective pharmacologic
inhibitors along with nonantioxidant therapies may improve the treatment outcomes
of patients with PH, while further investigation of the underlying mechanisms may
enable earlier detection of the disease.
PMID- 24350615
TI - Route to benzo- and pyrido-fused 1,2,4-triazinyl radicals via N'-(het)aryl-N'-[2
nitro(het)aryl]hydrazides.
AB - A two-step route to 1,3-disubstituted benzo- and pyrido-fused 1,2,4-triazinyl
radicals is presented. The route involves the N'-(2-nitroarylation) of easily
prepared N'-(het)arylhydrazides via nucleophilic aromatic substitution of 1-halo
2-nitroarenes, which in most cases gives N'-(het)aryl-N'-[2
nitro(het)aryl]hydrazides in good yields. Mild reduction of the nitro group
followed by an acid-mediated cyclodehydration gives the fused triazines, which
upon alkali treatment afford the desired radicals. Fifteen examples of radicals
are presented bearing a range of substituents at N-1, C-3, and C-7, including the
pyrid-2-yl and 8-aza analogues. This route to the N'-(het)aryl-N'-[2
nitro(het)aryl]hydrazides, which works well with benzo- and picolinohydrazides,
required a modification for aceto- and trifluoroacetohydrazides that involved a
multistep synthesis of asymmetrically 1,1-diaryl-substituted hydrazines.
PMID- 24350614
TI - Second-generation prophylactic HPV vaccines: successes and challenges.
AB - The role of HPV as the causative factor in cervical cancer has led to the
development of the HPV vaccines Gardasil and Cervarix. These vaccines effectively
protect against two HPV types associated with 70% of cervical cancer cases.
Despite this success, researchers continue to develop second-generation HPV
vaccines to protect against more HPV types and allow increased uptake in
developing countries. While a reformulated vaccine based on the current
technology is currently in clinical trials, another strategy consists of
targeting highly conserved epitopes in the minor capsid protein of HPV, L2.
Vaccines targeting L2 induce broadly neutralizing antibodies, capable of blocking
infection by a wide range of HPV types. Several vaccine designs have been
developed to optimize the display of L2 epitopes to the immune system and to
reduce the cost of manufacture and distribution. L2-based vaccines show
considerable promise as a potential next-generation HPV vaccine.
PMID- 24350617
TI - Implementation of a multicomponent psychosocial programme for persons with
dementia and their families in Norwegian municipalities: experiences from the
perspective of healthcare professionals who performed the intervention.
AB - BACKGROUND: A randomised controlled intervention study was conducted in 17
Norwegian municipalities to provide home-dwelling people with dementia and their
families with knowledge and skills to cope with the emerging problems and
stresses of everyday life. It included training health professionals to carry out
the intervention. Since little is known about possible benefits for health
professionals of participating in such a study in terms of knowledge and change
of practice as well as their views on whether the intervention is useful, we
carried out this study. AIM: To investigate the outcome of the study from the
perspective of the healthcare professionals who participated in the intervention.
METHOD: Interviews with 19 health professionals were performed during 2012, using
three focus groups and six individual interviews. The sample was purposive and
included informants aged 34-61 years from 13 municipalities. RESULTS: Three main
categories emerged: challenges, new knowledge and service development. The
category challenges details the challenges connected with professionals'
participation in the intervention and how they dealt with them and is described
in three subcategories. The category new knowledge demonstrates the knowledge the
professionals achieved while conducting the intervention and is described through
three subcategories. Service development presented how the informants'
experiences could contribute to improve the provision of care and details in one
subcategory. CONCLUSION: The results revealed a need for more knowledge among
health professionals about the situation of home-dwelling persons with dementia
and their families. The study indicated that health professionals must be more
aware of these persons' abilities to find their own solutions to their problems.
Structured individual interventions as well as group-based interventions in the
early stages of dementia and throughout the course of the disorder seem
beneficial. There is a need for better collaboration between the specialist
health services, GPs and health workers in the municipalities.
PMID- 24350616
TI - High mobility group box 1 acts as an adjuvant for tuberculosis subunit vaccines.
AB - In order to ensure an ample supply of quality candidate tuberculosis (TB) subunit
vaccines for clinical trials, it is imperative to develop new immunostimulatory
adjuvants. High Mobility Box Group 1 (HMGB1), a member of the alarmin group of
immunostimulatory proteins, is released by antigen-presenting cells under various
conditions and has been shown to induce T helper type 1 cytokines. We report that
HMGB1 is effective as an adjuvant to enhance the protective efficacy and cellular
immune response of TB subunit vaccines and that it is not dependent on the
interaction between HMGB1 and receptor for advanced glycation end products, a
major receptor for HMGB1. In the mouse model of TB, HMGB1 protein, when
formulated with dioctadecylammonium bromide and 6000 MW early secretory antigenic
target (ESAT-6), was protective as a subunit vaccine but did not protect as
molecular adjuvant in an ESAT-6-based DNA formulation. We then evaluated the
immunoprophylactic and protective potential of a fusion protein of HMGB1 and ESAT
6. The HMGB1-ESAT-6 fusion protein induced strong antigen-specific T helper type
1 cytokines at 30 days post-immunization. The fusion protein vaccine enhanced
activated and effector memory CD4 and CD8 T-cell responses in the lungs and
spleens of mice at 80 days post vaccination. Vaccination with the HMGB1-ESAT-6
fusion protein also resulted in elevated numbers of poly-functional CD4 T cells
co-expressing interleukin-2, interferon-gamma and tumour necrosis factor-alpha.
The potent cell-mediated immune response generated by the fusion protein
correlated with protection against subsequent challenge with Mycobacterium
tuberculosis in the mouse TB model.
PMID- 24350618
TI - Postoperative recurrence pattern and prognosis of patients with hepatocellular
carcinoma, with particular reference to the hepatitis viral infection status.
AB - BACKGROUND & AIMS: Various modalities have been employed effectively according to
the tumour recurrence status in patients with hepatocellular carcinoma (HCC)
undergoing hepatectomy. Therefore, their overall prognosis depends largely on the
pattern of recurrence/treatment. We investigated the patterns of recurrence and
prognosis in HCC patients, especially in relation to the hepatitis virus
infection status. METHODS: The study population comprised 244 patients with HCC
undergoing hepatectomy. Curative treatments, including repeated hepatectomies,
were performed for recurrences, whenever possible. Detailed information on
recurrences was collected until the recurrences exceeded Milan criteria. RESULTS:
The 5-year disease-free survival, survival within the Milan criteria and overall
survival were 38.4%, 56.3% and 74.5% respectively. In the comparison between
patients with hepatitis C and B virus-related HCC (HC-HCC: n = 122; and HB-HCC: n
= 45 respectively), the former showed lower disease-free (30.2% vs. 40.7% at 5
years, P = 0.061) and overall (65.7% vs. 89.7% at 5 years, P = 0.011) survivals;
they also showed a higher incidence of multinodular (>=4) intrahepatic
recurrences (19.4% vs. 5.3% at 3 years, P = 0.010). However, the incidences of
recurrences exceeding the Milan criteria because of other components were
comparable. Patients with HC-HCC showed a higher incidence of intrahepatic
recurrences characterized by multiple lesions and the difference became
increasingly more pronounced with time. CONCLUSIONS: Patients with HC-HCC were
associated with a higher carcinogenesis in the background liver than those with
HB-HCC, and this difference was aggravated with time after hepatic resection.
PMID- 24350619
TI - "Did you come?" A qualitative exploration of gender differences in beliefs,
experiences, and concerns regarding female orgasm occurrence during heterosexual
sexual interactions.
AB - This study explored gender differences in young adult heterosexual men's and
women's experiences, beliefs, and concerns regarding the occurrence or
nonoccurrence of orgasm during sexual interactions, with emphasis on the absence
of female orgasm during intercourse. Qualitative reports were obtained from five
female focus groups (N = 24, M age = 19.08) and five male focus groups (N = 21, M
age = 19.29), involving three to five participants per group. Transcripts of the
discussions were analyzed for emerging themes across focus group discussions.
Results indicated that, for both male and female participants, the most common
concern regarding lack of female orgasm in a partnered context focused on the
negative impact this might have on the male partner's ego. Male and female
participants also agreed that men have the physical responsibility to stimulate
their female partner to orgasm, while women have the psychological responsibility
of being mentally prepared to experience the orgasm. Men and women tended to
maintain different beliefs, however, regarding clitoral stimulation during
intercourse, as well as the importance of female orgasm for a woman's sexual
satisfaction in a partnered context. Findings suggest foci for sexual education.
PMID- 24350620
TI - An inorganic hole conductor for organo-lead halide perovskite solar cells.
Improved hole conductivity with copper iodide.
AB - Organo-lead halide perovskite solar cells have emerged as one of the most
promising candidates for the next generation of solar cells. To date, these
perovskite thin film solar cells have exclusively employed organic hole
conducting polymers which are often expensive and have low hole mobility. In a
quest to explore new inorganic hole conducting materials for these perovskite
based thin film photovoltaics, we have identified copper iodide as a possible
alternative. Using copper iodide, we have succeeded in achieving a promising
power conversion efficiency of 6.0% with excellent photocurrent stability. The
open-circuit voltage, compared to the best spiro-OMeTAD devices, remains low and
is attributed to higher recombination in CuI devices as determined by impedance
spectroscopy. However, impedance spectroscopy revealed that CuI exhibits 2 orders
of magnitude higher electrical conductivity than spiro-OMeTAD which allows for
significantly higher fill factors. Reducing the recombination in these devices
could render CuI as a cost-effective competitor to spiro-OMeTAD in perovskite
solar cells.
PMID- 24350622
TI - Effect of solvent polarizability on the assembly and ordering of nanoscale
polyhedral oligomeric silsesquioxane films.
AB - Understanding the factors that affect molecular self-assembly is crucial to
building designed nanoscale structures. We have deposited nanoscale films of
polyhedral oligomeric silsesquioxane (POSS) onto polished silicon substrates from
a range of organic solvents. We studied these films using synchrotron X-ray
reflectivity and found that dip-coating from benzene, toluene, or chloroform
results in near-substrate ordering only, but when acetone, hexane, or THF is
used, self-assembled layers are formed throughout the entire deposited film. We
conclude that solvent polarizability is the factor that determines the alignment
of the POSS molecules. We have successfully tested this prediction using
additional solvents selected on the basis of their calculated polarizabilities.
PMID- 24350621
TI - Biased gene expression in early honeybee larval development.
AB - BACKGROUND: Female larvae of the honeybee (Apis mellifera) develop into either
queens or workers depending on nutrition. This nutritional stimulus triggers
different developmental trajectories, resulting in adults that differ from each
other in physiology, behaviour and life span. RESULTS: To understand how these
trajectories are established we have generated a comprehensive atlas of gene
expression throughout larval development. We found substantial differences in
gene expression between worker and queen-destined larvae at 6 hours after
hatching. Some of these early changes in gene expression are maintained
throughout larval development, indicating that caste-specific developmental
trajectories are established much earlier than previously thought. Within our
gene expression data we identified processes that potentially underlie caste
differentiation. Queen-destined larvae have higher expression of genes involved
in transcription, translation and protein folding early in development with a
later switch to genes involved in energy generation. Using RNA interference, we
were able to demonstrate that one of these genes, hexamerin 70b, has a role in
caste differentiation. Both queen and worker developmental trajectories are
associated with the expression of genes that have alternative splice variants,
although only a single variant of a gene tends to be differentially expressed in
a given caste. CONCLUSIONS: Our data, based on the biases in gene expression
early in development together with published data, supports the idea that caste
development in the honeybee consists of two phases; an initial biased phase of
development, where larvae can still switch to the other caste by differential
feeding, followed by commitment to a particular developmental trajectory.
PMID- 24350623
TI - Brain on the stage - spotlight on nervous system development in zebrafish: EMBO
practical course, KIT, Sept. 2013.
AB - During the EMBO course 'Imaging of Neural Development in Zebrafish', held on
September 9-15th 2013, researchers from different backgrounds shared their latest
results, ideas and practical expertise on zebrafish as a model to address open
questions regarding nervous system development.
PMID- 24350624
TI - Effect of pubic bone marrow edema on recovery from endoscopic surgery for
athletic pubalgia.
AB - Athletic pubalgia (sportsman's hernia) is often repaired by surgery. The presence
of pubic bone marrow edema (BME) in magnetic resonance imaging (MRI) may effect
on the outcome of surgery. Surgical treatment of 30 patients with athletic
pubalgia was performed by placement of totally extraperitoneal endoscopic mesh
behind the painful groin area. The presence of pre-operative BME was graded from
0 to 3 using MRI and correlated to post-operative pain scores and recovery to
sports activity 2 years after operation. The operated athletes participated in
our previous prospective randomized study. The athletes with (n = 21) or without
(n = 9) pubic BME had similar patients' characteristics and pain scores before
surgery. Periostic and intraosseous edema at symphysis pubis was related to
increase of post-operative pain scores only at 3 months after surgery (P = 0.03)
but not to long-term recovery. Two years after surgery, three athletes in the BME
group and three in the normal MRI group needed occasionally pain medication for
chronic groin pain, and 87% were playing at the same level as before surgery.
This study indicates that the presence of pubic BME had no remarkable long-term
effect on recovery from endoscopic surgical treatment of athletic pubalgia.
PMID- 24350625
TI - Exploring transition pathway and free-energy profile of large-scale protein
conformational change by combining normal mode analysis and umbrella sampling
molecular dynamics.
AB - Large-scale conformational changes of proteins are usually associated with the
binding of ligands. Because the conformational changes are often related to the
biological functions of proteins, understanding the molecular mechanisms of these
motions and the effects of ligand binding becomes very necessary. In the present
study, we use the combination of normal-mode analysis and umbrella sampling
molecular dynamics simulation to delineate the atomically detailed conformational
transition pathways and the associated free-energy landscapes for three well
known protein systems, viz., adenylate kinase (AdK), calmodulin (CaM), and
p38alpha kinase in the absence and presence of respective ligands. For each
protein under study, the transient conformations along the conformational
transition pathway and thermodynamic observables are in agreement with
experimentally and computationally determined ones. The calculated free-energy
profiles reveal that AdK and CaM are intrinsically flexible in structures without
obvious energy barrier, and their ligand binding shifts the equilibrium from the
ligand-free to ligand-bound conformation (population shift mechanism). In
contrast, the ligand binding to p38alpha leads to a large change in free-energy
barrier (DeltaDeltaG ~ 7 kcal/mol), promoting the transition from DFG-in to DFG
out conformation (induced fit mechanism). Moreover, the effect of the protonation
of D168 on the conformational change of p38alpha is also studied, which reduces
the free-energy difference between the two functional states of p38alpha and thus
further facilitates the conformational interconversion. Therefore, the present
study suggests that the detailed mechanism of ligand binding and the associated
conformational transition is not uniform for all kinds of proteins but correlated
to their respective biological functions.
PMID- 24350626
TI - Production and characterization of monoclonal antibodies against aflatoxin B1.
AB - In this article, we embarked on production of mouse monoclonal antibodies against
aflatoxin B1 which is the most commonly occurring fungal toxin in food and feed
products. After immunization and fusion with myloma cells, two stable clones
(A218 and B319) were selected. Isotyping showed that these monoclonal antibodies
(mAbs) were IgG2b with kappa light chains. The affinity of A218 and B319 clons
were 5*10(11) M(-1) and 6*10(9) M(-1), respectively. Competitive indirect ELISA
results indicated these mAbs had complete (100%) cross-reaction with four major
types of aflatoxins: B1, B2, G1, and G2. These mAbs could be used for immunoassay
measurement of aflatoxins with high affinity and low detection limits.
PMID- 24350627
TI - Risk factors for nontuberculous mycobacterial infections in solid organ
transplant recipients: a case-control study.
AB - BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) disease in
solid organ transplant recipients is poorly defined. METHODS: We identified all
solid organ transplant recipients with NTM disease at a single center over a 7.5
year period, and collected data on patient demographics, co-morbidities,
immunosuppressive medications, and rejection. We conducted a case-control study
to identify risk factors for disease, matching 3 control patients to each case
patient by date of transplantation. RESULTS: A total of 34 cases of NTM disease
occurred during the study period, involving 6 single lung, 13 bilateral lung, 8
heart, 4 liver, 2 kidney, and 1 pancreas-kidney recipients. Cases were
predominantly male (24/34), with a median age of 55 years (interquartile range
[IQR]: 46-61 years), and developed after a median of 8 months post
transplantation (IQR: 2-87 months). Mycobacterium abscessus and Mycobacterium
avium complex were the most common pathogens, and the lung (including pleura) was
the most common site of disease. In the adjusted case-control analysis, lung
transplant recipients had the highest risk of NTM disease. CONCLUSIONS:
Additional studies are needed to evaluate the role of targeted surveillance
measures for NTM disease in high-risk patients, particularly lung transplant
recipients, and to characterize the mechanisms of disease acquisition.
PMID- 24350628
TI - Estimation of time-dependent association for bivariate failure times in the
presence of a competing risk.
AB - This article targets the estimation of a time-dependent association measure for
bivariate failure times, the conditional cause-specific hazards ratio (CCSHR),
which is a generalization of the conditional hazards ratio (CHR) to accommodate
competing risks data. We model the CCSHR as a parametric regression function of
time and event causes and leave all other aspects of the joint distribution of
the failure times unspecified. We develop a pseudo-likelihood estimation
procedure for model fitting and inference and establish the asymptotic properties
of the estimators. We assess the finite-sample properties of the proposed
estimators against the estimators obtained from a moment-based estimating
equation approach. Data from the Cache County study on dementia are used to
illustrate the proposed methodology.
PMID- 24350629
TI - Evaluation of heme peripheral group interactions in extremely low-dielectric
constant media and their contributions to the heme reduction potential.
AB - In this study, we measured the contributions of the ionization of the heme
propionates to the reduction potentials of heme b and heme a (bis)N
methylimidazole complexes in various low-dielectric constant conditions.
Additionally, we measured the effects of H-bond to the heme a formyl group on the
reduction potential of the heme. The performed electrochemical measurements show
that ionization of the heme propionates lead to the largest redox change in
dichloromethane with no electrolyte. The measured reduction potential changes for
heme b and heme a were -55 and -47 mV (+/-10 mV) per ionized propionate,
respectively. For heme a, the study demonstrates how the dielectric constant of
the medium is important in the magnification of the DeltapKa upon redox-linked
ionization of the heme propionates and their roles in the proton pump of
cytochrome c oxidase.
PMID- 24350631
TI - An unusual termination of a wide complex tachycardia.
PMID- 24350632
TI - Past suicide attempts in depressed inpatients: clinical versus research
assessment.
AB - The objective of this study was to compare structured clinical assessment versus
research measurement of suicidal risk among inpatients with major depression.
Fifty depressed inpatients underwent a structured clinical and an independent
research assessment of suicidal risk. Agreement between both assessments and its
impact upon time to first readmission was tested. A false negative rate of 25% in
the clinical screening of past suicide attempts was associated with older age,
concealment, and reported lower frequency of suicidal thoughts. Mean times to
first readmission (2.5 years follow-up) were 74 weeks (discordant responders) and
118 weeks (concordant responders). A failure to detect 25% of patients with past
suicide attempt history in the clinical assessment was associated with older age
and concealment of suicidal thoughts.
PMID- 24350633
TI - Is asymmetric dimethylarginine associated with being born small and large for
gestational age?
AB - Low and high birth weights have been linked to increased susceptibility to
cardiovascular and metabolic alterations. However, the natural history of
cardiometabolic disturbances in children born small (SGA) and large (LGA) for
gestational age is still unclear and no reliable biomarker of cardiovascular risk
has definitively been identified in these subjects. Interestingly, asymmetric
dimethylarginine (ADMA), antagonist of nitric oxide (NO) production, has been
recognized as novel cardiovascular marker able to identify subjects at higher
risk of health disturbances. Despite the well-described role of ADMA as a
predictor of degenerative disease in adults, its potential application in
pediatrics, and specifically in SGA and LGA children, has not been explored as
only few data in preterm infants and SGA newborns are available. Therefore, we
investigated potential alterations in circulating ADMA and NO levels in SGA and
LGA children compared with those born appropriate (AGA) for gestational age. Of
note, ADMA was significantly higher in SGA and LGA children than AGA peers.
Intriguingly, SGA and LGA categories as well as insulin resistance were
independently related to ADMA. Our observations lead to the intriguing hypothesis
that ADMA could be involved in the development of cardiometabolic alterations in
SGA and LGA children already during the prepubertal age.
PMID- 24350634
TI - Design and development of novel lipid based gastroretentive delivery system:
response surface analysis, in-vivo imaging and pharmacokinetic study.
AB - Famotidine HCl has low bioavailability (40-45%) due to its narrow absorption
window and low solubility in intestinal pH. Lipids were utilized in the
formulation of novel gastroretentive dosage forms to increase the availability of
famotidine HCl at its absorption site. Novel non-swellable gastroretentive lipid
disks (D) and swellable compression coated tablets with a lipid core (T) were
prepared. Formulae were characterized by friability testing, in-vitro buoyancy,
in-vitro drug release and scanning electron microscopy (SEM). Factorial designs
of 2(2 )* 3(1) and 3(2) were planned for the optimization of disks and tablets,
respectively, using Design-Expert(r) software. X-ray imaging was used for the in
vivo visualization of the selected formula in human gastrointestinal tract (GIT).
Moreover, a bioavailability study was performed in healthy human volunteers using
the optimized disk formula (D10). Results showed that formulae D10 (containing
stearyl alcohol and polyethylene glycol in a ratio of 9:1 w/w) and T7 (containing
polyethylene oxide only) had highest desirability values (0.684 and 0.842,
respectively). Lipids achieved instantaneous floating and sustained the release
of famotidine HCl over a prolonged period of time with significant
bioavailability enhancement.
PMID- 24350630
TI - Intrigues and intricacies of the biosynthetic pathways for the enzymatic
quinocofactors: PQQ, TTQ, CTQ, TPQ, and LTQ.
PMID- 24350636
TI - Searching for emotion or race: task-irrelevant facial cues have asymmetrical
effects.
AB - Facial cues of threat such as anger and other race membership are detected
preferentially in visual search tasks. However, it remains unclear whether these
facial cues interact in visual search. If both cues equally facilitate search, a
symmetrical interaction would be predicted; anger cues should facilitate
detection of other race faces and cues of other race membership should facilitate
detection of anger. Past research investigating this race by emotional expression
interaction in categorisation tasks revealed an asymmetrical interaction. This
suggests that cues of other race membership may facilitate the detection of angry
faces but not vice versa. Utilising the same stimuli and procedures across two
search tasks, participants were asked to search for targets defined by either
race or emotional expression. Contrary to the results revealed in the
categorisation paradigm, cues of anger facilitated detection of other race faces
whereas differences in race did not differentially influence detection of emotion
targets.
PMID- 24350637
TI - Active surveillance for adverse events following immunization.
AB - Comprehensive surveillance of adverse events following immunization (AEFI) is
required to detect potential serious adverse events that may not be identified in
prelicensure vaccine trials. Surveillance systems have traditionally been
passive, relying upon spontaneous reporting, but increasingly active surveillance
and supplemental strategies are being incorporated into vaccine safety programs.
These include active screening for targeted conditions of interest (e.g.,
hospitalization), monitoring of new data sources and real-time methodologies to
detect changes in vaccine safety data in these sources. The role of improved
causality assessment in AEFI surveillance is discussed, with its important role
in determining whether a temporal association may have occurred by chance alone.
Strong local vaccine safety networks are required to support national
immunization programs, with recent progress in developing a framework for low-
and middle-income countries. Global collaboration is increasingly required to
address challenges in active AEFI surveillance, particularly for rare serious
adverse events.
PMID- 24350635
TI - Magnesium sulphate for fetal neuroprotection: a cost-effectiveness analysis.
AB - BACKGROUND: The aim of this study was to assess the cost-effectiveness of
administering magnesium sulphate to patients in whom preterm birth at < 32+0
weeks gestation is either imminent or threatened for the purpose of fetal
neuroprotection. METHODS: Multiple decision tree models and probabilistic
sensitivity analyses were used to compare the administration of magnesium
sulphate with the alternative of no treatment. Two separate cost perspectives
were utilized in this series of analyses: a health system and a societal
perspective. In addition, two separate measures of effectiveness were utilized:
cases of cerebral palsy (CP) averted and quality-adjusted life years (QALYs).
RESULTS: From a health system and a societal perspective, respectively, a savings
of $2,242 and $112,602 is obtained for each QALY gained and a savings of $30,942
and $1,554,198 is obtained for each case of CP averted when magnesium sulphate is
administered to patients in whom preterm birth is imminent. From a health system
perspective and a societal perspective, respectively, a cost of $2,083 is
incurred and a savings of $108,277 is obtained for each QALY gained and a cost of
$28,755 is incurred and a savings of $1,494,500 is obtained for each case of CP
averted when magnesium sulphate is administered to patients in whom preterm birth
is threatened. CONCLUSIONS: Administration of magnesium sulphate to patients in
whom preterm birth is imminent is a dominant (i.e. cost-effective) strategy, no
matter what cost perspective or measure of effectiveness is used. Administration
of magnesium sulphate to patients in whom preterm birth is threatened is a
dominant strategy from a societal perspective and is very likely to be cost
effective from a health system perspective.
PMID- 24350638
TI - Digital dissection - using contrast-enhanced computed tomography scanning to
elucidate hard- and soft-tissue anatomy in the Common Buzzard Buteo buteo.
AB - Gross dissection has a long history as a tool for the study of human or animal
soft- and hard-tissue anatomy. However, apart from being a time-consuming and
invasive method, dissection is often unsuitable for very small specimens and
often cannot capture spatial relationships of the individual soft-tissue
structures. The handful of comprehensive studies on avian anatomy using
traditional dissection techniques focus nearly exclusively on domestic birds,
whereas raptorial birds, and in particular their cranial soft tissues, are
essentially absent from the literature. Here, we digitally dissect, identify, and
document the soft-tissue anatomy of the Common Buzzard (Buteo buteo) in detail,
using the new approach of contrast-enhanced computed tomography using Lugol's
iodine. The architecture of different muscle systems (adductor, depressor,
ocular, hyoid, neck musculature), neurovascular, and other soft-tissue structures
is three-dimensionally visualised and described in unprecedented detail. The
three-dimensional model is further presented as an interactive PDF to facilitate
the dissemination and accessibility of anatomical data. Due to the digital nature
of the data derived from the computed tomography scanning and segmentation
processes, these methods hold the potential for further computational analyses
beyond descriptive and illustrative proposes.
PMID- 24350639
TI - Late onset of clinically apparent central vein stenosis due to previous central
venous catheter in a patient with inherited thrombophilia.
AB - We describe a case of a patient with a functional kidney transplant who was
admitted to our department with clinically evident central vein stenosis (CVS) 7
years after the removal of a central venous catheter (CVC) from the right
internal jugular vein. The catheter was used as a hemodialysis access for a 2
month period. In the interval before his last admission, the patient suffered two
episodes of deep vein thrombosis. Investigation revealed heterozygosity for
factor V Leiden, the most common inherited thrombophilia encountered in 5% of
Caucasians, and anticoagulation treatment was started. Magnetic resonance
angiography showed stenosis just after the convergence of the right subclavian
vein with the internal jugular vein to the innominate vein. Transluminal
angioplasty restored venous patency and right upper arm edema resolved.
Coexistence of CVS, accompanied by hemodynamic changes and endothelial
dysfunction, with thrombophilia fulfill all the elements of the Virchow's triad.
Therefore, the patient was at great risk for central vein thrombosis, from which
he was possibly protected by the early administration of anticoagulant treatment.
This case indicates that CVS can be asymptomatic for several years after CVC
removal and also raises the question if thrombophilia workup and investigation
for CVS may be beneficial in every patient with CVC placement in order to avoid
any harmful outcomes.
PMID- 24350640
TI - Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: is
lobectomy sufficient for tumours >=1 cm?
PMID- 24350641
TI - Porous organic material from discotic tricarboxyamide: side chain-core
interactions.
AB - The benzene-1,3,5-tricarboxyamide containing three l-methionine (1) self-assemble
through 3-fold amide-amide hydrogen bonds and pi-pi stacking to fabricate one
dimensional nanorod like structure. However, the tyrosine analogue (2) carrying
multiple H-bonding side chains lost the C3 symmetry and 3-fold amide-amide
hydrogen bonds and developed a porous structure. The porous material exhibits ten
times more N2 sorption (155 cc/g) than the columnar one, indicating that side
chain-core interactions have a drastic effect on structure and function.
PMID- 24350642
TI - Components of a hyperthermia clinic: recommendations for staffing, equipment, and
treatment monitoring.
AB - Like other technically sophisticated medical endeavours, a hyperthermia clinic
relies on skilled staffing. Physicians, physicists and technologists perform
multiple tasks to ensure properly functioning equipment, appropriate patient
selection, and to plan and administer this treatment. This paper reviews the
competencies and tasks that are used in a hyperthermia clinic.
PMID- 24350643
TI - Chemical pyrophosphorylation of functionally diverse peptides.
AB - A highly selective and convenient method for the synthesis of pyrophosphopeptides
in solution is reported. The remarkable compatibility with functional groups
(alcohol, thiol, amine, carboxylic acid) in the peptide substrates suggests that
the intrinsic nucleophilicity of the phosphoserine residue is much higher than
previously appreciated. Because the methodology operates in polar solvents,
including water, a broad range of pyrophosphopeptides can be accessed. We
envision these peptides will find widespread applications in the development of
mass spectrometry and antibody-based detection methods for pyrophosphoproteins.
PMID- 24350645
TI - Tailored Gallium(III) chelator NOPO: synthesis, characterization, bioconjugation,
and application in preclinical Ga-68-PET imaging.
AB - The bifunctional chelator NOPO (1,4,7-triazacyclononane-1,4
bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2
carboxyethyl)phosphinic acid]) shows remarkably high Ga(III) complexation
efficiency and comprises one carboxylic acid moiety which is not involved into
metal ion coordination. An improved synthetic protocol affords NOPO with 45%
overall yield. Stepwise protonation constants (log Ka), determined by
potentiometry, are 11.96, 5.22, 3.77, and 1.54; the stability constant of the
Ga(III) complex is log KGaL = 25.0. Within 5 min, (68)Ga(III) incorporation by
NOPO is virtually quantitative at room temperature between pH 3 and 4, and at 95
degrees C at pH ranging from 0.5 to 7, at NOPO concentrations of 30 MUM and 10
MUM, respectively. During amide bond formation at the distant carboxylate using
the HATU coupling reagent, an intramolecular phosphinic acid ester
(phosphilactone) is formed, which is cleaved during (68)Ga complexation or in
acidic media, such as trifluoroacetic acid (TFA). Phosphilactone formation can
also be suppressed by complexation of Zn(2+) prior to conjugation, the resulting
zinc-containing conjugates nevertheless being suitable for direct (68)Ga
labeling. In AR42J (rat pancreatic carcinoma) xenografted CD-1 nude mice, (68)Ga
labeled NOPO-NaI(3)-octreotide conjugate ((68)Ga-NOPO-NOC) showed high and fully
blockable tumor uptake (13.9 +/- 5% ID/g, 120 min p.i., compared to 0.9 +/- 0.4%
ID/g with 5 mg/kg of nonlabeled peptide). Uptake in other tissues was generally
below 3% ID/g, except appearance of excretion-related activity accumulation in
kidneys. NOPO-functionalized compounds tend to be more hydrophilic than the
corresponding DOTA- and NODAGA-conjugates, thus promoting fast and extensive
renal excretion of (68)Ga-NOPO-radiopharmaceuticals. NOPO-functionalized peptides
provide suitable pharmacokinetics in vivo and meet all requirements for efficient
(68)Ga-labeling even at room temperature in a kit-like manner.
PMID- 24350644
TI - An overview of gene expression dynamics during early ovarian folliculogenesis:
specificity of follicular compartments and bi-directional dialog.
AB - BACKGROUND: Successful early folliculogenesis is crucial for female reproductive
function. It requires appropriate gene specific expression of the different types
of ovarian cells at different developmental stages. To date, most gene expression
studies on the ovary were conducted in rodents and did not distinguish the type
of cell. In mono-ovulating species, few studies have addressed gene expression
profiles and mainly concerned human oocytes. RESULTS: We used a laser capture
microdissection method combined with RNA-seq technology to explore the
transcriptome in oocytes and granulosa cells (GCs) during development of the
sheep ovarian follicle. We first documented the expression profile of 15 349
genes, then focused on the 5 129 genes showing differential expression between
oocytes and GCs. Enriched functional categories such as oocyte meiotic arrest and
GC steroid synthesis reflect two distinct cell fates. We identified the
implication of GC signal transduction pathways such as SHH, WNT and RHO GTPase.
In addition, signaling pathways (VEGF, NOTCH, IGF1, etc.) and GC transzonal
projections suggest the existence of complex cell-cell interactions. Finally, we
highlighted several transcription regulators and specifically expressed genes
that likely play an important role in early folliculogenesis. CONCLUSIONS: To our
knowledge, this is the first comprehensive exploration of transcriptomes derived
from in vivo oocytes and GCs at key stages in early follicular development in
sheep. Collectively, our data advance our understanding of early folliculogenesis
in mono-ovulating species and will be a valuable resource for unraveling human
ovarian dysfunction such as premature ovarian failure (POF).
PMID- 24350646
TI - Effect of PEGylation on drug entry into lipid bilayer.
AB - Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of
drug molecules to increase their bloodstream lifetime, hence efficacy. However,
the interactions between the PEGylated drugs and biomembranes are not clearly
understood. In this study, we employed atomic-scale molecular dynamics (MD)
simulations to consider the behavior of two drug molecules functionalized with
PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging
to the isoflavone family) in the presence of a lipid bilayer. The commonly held
view is that functionalization of a drug molecule with a polymer acts as an
entropic barrier, inhibiting the penetration of the drug molecule through a cell
membrane. Our results indicate that in the bloodstream there is an additional
source of electrostatic repulsive interactions between the PEGylated drugs and
the lipid bilayer. Both the PEG chain and lipids can bind Na(+) ions, thus
effectively becoming positively charged molecules. This leads to an extra
repulsive effect resulting from the presence of salt in the bloodstream. Thus,
our study sheds further light on the role of PEG in drug delivery.
PMID- 24350647
TI - Successful penile reconstruction after multimodal therapy in patients with
primitive neuroectodermal tumor originating from the penis.
AB - We herein present an extremely rare case of primitive neuroectodermal tumor
originating in the penis. A 16-year-old male adolescent presented with painful
penile swelling. Pathological, immunohistochemical and cytogenetical examinations
of the specimens obtained from total penectomy confirmed the diagnosis of
primitive neuroectodermal tumor. After total penectomy, the patient received
adjuvant chemotherapy with ifosfamide-based regimen for 48 weeks. As a series of
therapies, the patient underwent penile reconstruction surgery after completing
adjuvant chemotherapy. The patient has not shown any evidence of recurrence for
the 7 years after penile reconstruction surgery, and voiding function is
completely normal. A favorable outcome was observed by multimodal therapy
including aggressive resection for local control, intensive adjuvant
chemotherapy, and penile reconstruction with cosmetic and functional success.
Similar therapeutic approaches might be selected for children with primary
malignant tumors of the penis.
PMID- 24350648
TI - First reported multistate human Q fever outbreak in the United States, 2011.
AB - In April, 2011, the Q fever bacterium Coxiella burnetii was identified at a
Washington farm where an abortion storm took place among goats. Soon after, Q
fever cases were reported among visitors to the farm from Washington and Montana.
A cross-sectional investigation was conducted among humans and goats associated
with the index farm or with 16 other farms that purchased goats from the index
farm or housed goats at the index farm for breeding purposes. Questionnaire data
were analyzed, along with human and goat specimens collected for evidence of C.
burnetii infection. Twenty-one persons (19%) of the 109-person cohort from
Washington and Montana met the outbreak case definition of an epidemiologic link
to the index farm and a C. burnetii Phase II immunoglobulin G (IgG) titer >=1:128
by immunofluorescence assay. Seventy-one percent of cases (15 of 21) were
symptomatic, compared with approximately 50% during previous Q fever outbreaks.
National Q fever surveillance reports increase in frequency with age, but 29% (6
of 21) of cases during this outbreak occurred in children aged <14 years. Goat
specific Q fever risk factors included direct contact with a newborn (prevalence
ratio [PR] 10.7; confidence interval [CI] 1.5, 77.4), exposure to a newborn that
died (PR 5.5; CI 1.7, 18.2), exposure to a weak newborn (PR 4.4; CI 1.7, 11.6),
living on a property with goats (PR 4.2; CI 1.3, 13.9), and direct contact with
birth/afterbirth products (PR 2.8; CI 1.1, 6.9). Evidence of C. burnetii
infection was detected in all 17 goat herds sampled (13 Washington, 3 Montana, 1
Oregon) by PCR and/or enzyme-linked immunosorbent assay. Following this
investigation, Washington and Montana implemented a herd management plan to
encourage best-management practices among livestock owners, reduce the potential
for future outbreaks, and promote continued communication between state public
health and agricultural authorities.
PMID- 24350649
TI - Simultaneous determination of 36 pesticide residues in spinach and cauliflower by
LC-MS/MS using multi-walled carbon nanotubes-based dispersive solid-phase clean
up.
AB - A multi-residue method based on a modified QuEChERS sample preparation with multi
walled carbon nanotubes (MWCNTs) as reversed-dispersive solid-phase extraction (r
DSPE) material and LC-MS/MS determination by MRM mode was validated for 36
representative pesticides in spinach and cauliflower. It was demonstrated that
MWCNTs can be used as effective r-DSPE materials with the QuEChERS method for the
clean-up of extract from different matrices. However, MWCNTs could absorb
pyrimethanil, diflubenzuron, and chlorbenzuron in both spinach and cauliflower,
which leads to the low recoveries compared with PSA. The LODs and LOQs for 36
pesticides ranged from 0.1 to 5 MUg kg(-1) and from 2 to 30 MUg kg(-1),
respectively. Good linearity was found for all pesticides with coefficients
better than 0.995 in a range of 0.02-0.5 mg l(-1). The developed method with
MWCNTs clean-up was successfully used to determine the 36 pesticides in real
samples.
PMID- 24350650
TI - Impact of myocardial viability and left ventricular lead location on clinical
outcome in cardiac resynchronization therapy recipients with ischemic
cardiomyopathy.
AB - INTRODUCTION: Cardiac resynchronization therapy (CRT) recipients with ischemic
cardiomyopathy (ICM) have scar segments that may limit ventricular
resynchronization and clinical response. The impact of myocardial viability at
the left ventricular (LV) pacing site on CRT response is poorly elucidated.
METHODS AND RESULTS: A retrospective cohort of 160 ICM patients with single
photon emission computed tomography-myocardial perfusion imaging before device
implantation were included. Coronary venous angiography and chest radiographs
helped classify segmental location of LV lead (LVL). The primary outcome was a
composite of heart failure (HF) hospitalization and mortality at 3 years, and
secondary outcome was change in systolic function at 6 months. The patients were
divided into groups based on the myocardial substrate at the site of LVL: LVL on
or adjacent to (1) normal myocardium (LVL-N, n = 64), (2) segmental scar (LVL-S,
n = 62), and (3) scar and ischemia (LVL-SI, n = 34). Upon follow-up, 75 (47%)
patients reached primary endpoint with a higher incidence noted in LVL-S (60%),
and LVL-SI (53%), compared to 31% in LVL-N (P = 0.004). Kaplan Meier method
demonstrated poor event free survival for primary outcome in LVL-S (P = 0.002),
and LVL-SI (P = 0.03). In Cox proportional hazard model, LVL-S (HR: 2.26, P =
0.004), and LVL-SI (1.9, P = 0.047) were independent predictors of primary
outcome. CONCLUSION: In CRT recipients with ICM, scar and reversible ischemia in
or adjacent to LV pacing site were independent predictors of HF hospitalization
and death.
PMID- 24350651
TI - An immunohistochemical assay on human tissue using a human primary antibody.
AB - Non human antibodies administered to human patients often generate anti-antibody
responses, leading in extreme cases to anaphylactic shock. Completely human
antibodies are therefore favored over their murine, chimeric and humanized
counterparts. However, the accurate evaluation of human antibodies on human
tissue samples cannot be achieved using indirect immunohistochemical methods
because of endogenous immunoglobulins that are co-detected by the secondary
antibodies. Direct detection is often used instead, but this lacks the signal
amplification conferred by the secondary antibody and is therefore less
sensitive. We developed a simple fluorescence-based indirect immunohistochemical
method that allows human primary antibodies bound specifically to their target
antigens in human tissue samples to be detected clearly and without interfering
background staining. This approach involves a biotinylated human primary antibody
(H10(Biotin)) and Cy3-conjugated streptavidin (Strep(Cy3)). We tested the
protocol using a human carcinoembryonic antigen (CEA) specific IgG1 (H10). We
identified an exposure time threshold that allowed the elimination of low
Strep(Cy3) background staining, yet achieved sufficient signal amplification to
make our approach four times more sensitive than comparable direct
immunohistochemical procedures. The principle of this indirect
immunohistochemical assay should be transferable to other species allowing the
specific and sensitive detection of any primary antibody on homologous tissues.
PMID- 24350653
TI - Conformational polymorphism.
PMID- 24350652
TI - Failure of malaria chemoprophylaxis with mefloquine in an oversize traveller to
Mozambique.
AB - A case of failure of mefloquine prophylaxis in an oversize traveller, who
correctly took the drug. This case seems to be attributed to mefloquine
resistance, however it is suggested that mefloquine dosage should be modulated by
body weight, as is already indicated by some authorities.
PMID- 24350654
TI - First manic episode associated with use of human chorionic gonadotropin for
obesity: a case report.
AB - BACKGROUND: Although highly controversial, the treatment of obesity with
exogenous human chorionic gonadotropin (HCG) remains popular in the USA. We
report the case of a patient whose first manic episode was associated with the
use of HCG for weight loss. CASE REPORT: A 32-year-old female patient was
admitted to our psychiatric inpatient unit due to a two-week history of manic
symptoms. She had no previous history of manic or hypomanic episodes and had
completed a 45-day course of sublingual HCG for weight loss immediately prior to
the onset of the manic episode. The patient was treated with lithium carbonate
and aripiprazole, and progressed with improvement in the symptoms. CONCLUSION:
While it is not possible to definitively link the HCG use to the development of
mania, available evidence suggests that HCG may have a contributing role in
triggering manic symptomatology.
PMID- 24350655
TI - An evaluation of independent component analyses with an application to resting
state fMRI.
AB - We examine differences between independent component analyses (ICAs) arising from
different assumptions, measures of dependence, and starting points of the
algorithms. ICA is a popular method with diverse applications including artifact
removal in electrophysiology data, feature extraction in microarray data, and
identifying brain networks in functional magnetic resonance imaging (fMRI). ICA
can be viewed as a generalization of principal component analysis (PCA) that
takes into account higher-order cross-correlations. Whereas the PCA solution is
unique, there are many ICA methods-whose solutions may differ. Infomax, FastICA,
and JADE are commonly applied to fMRI studies, with FastICA being arguably the
most popular. Hastie and Tibshirani (2003) demonstrated that ProDenICA
outperformed FastICA in simulations with two components. We introduce the
application of ProDenICA to simulations with more components and to fMRI data.
ProDenICA was more accurate in simulations, and we identified differences between
biologically meaningful ICs from ProDenICA versus other methods in the fMRI
analysis. ICA methods require nonconvex optimization, yet current practices do
not recognize the importance of, nor adequately address sensitivity to, initial
values. We found that local optima led to dramatically different estimates in
both simulations and group ICA of fMRI, and we provide evidence that the global
optimum from ProDenICA is the best estimate. We applied a modification of the
Hungarian (Kuhn-Munkres) algorithm to match ICs from multiple estimates, thereby
gaining novel insights into how brain networks vary in their sensitivity to
initial values and ICA method.
PMID- 24350656
TI - Genotype-dependency of butyrate efficacy in children with congenital chloride
diarrhea.
AB - BACKGROUND: Congenital chloride diarrhea (CLD) is an autosomal recessive disorder
characterized by life-long, severe diarrhea with intestinal Cl- malabsorption. It
results from a reduced activity of the down regulated in adenoma exchanger (DRA),
due to mutations in the solute carrier family 26, member 3 (SLC26A3) gene.
Currently available therapies are not able to limit the severity of diarrhea in
CLD. Conflicting results have been reported on the therapeutic efficacy of oral
butyrate. METHODS: We investigated the effect of oral butyrate (100 mg/kg/day) in
seven CLD children with different SLC26A3 genotypes. Nasal epithelial cells were
obtained to assess the effect of butyrate on the expression of the two main Cl-
transporters: DRA and putative anion transporter-1 (PAT-1). RESULTS: A variable
clinical response to butyrate was observed regarding the stool pattern and fecal
ion loss. The best response was observed in subjects with missense and deletion
mutations. Variable response to butyrate was also observed on SLC26A3 (DRA) and
SLC26A6 (PAT1) gene expression in nasal epithelial cells of CLD patients.
CONCLUSIONS: We demonstrate a genotype-dependency for butyrate therapeutic
efficacy in CLD. The effect of butyrate is related in part on a different
modulation of the expression of the two main apical membrane Cl- exchangers of
epithelial cells, members of the SLC26 anion family. TRIAL REGISTRATION:
Australian New Zealand Clinical trial Registry ACTRN12613000450718.
PMID- 24350657
TI - The significance of FM associations for women with FM.
AB - PURPOSE: Living with fibromyalgia (FM) means living with a long-term pain
syndrome that is invisible to others. Support and understanding from others seem
to be important to managing the affected daily life. The aim of this study was to
describe the significance of FM associations for women with FM. METHODS: Data
collection was carried out through focus group discussions with seventeen women
with FM. Data were analyzed through thematic content analysis. RESULTS: The
findings show that women experienced associations for people with FM as important
as they gave access to contacts with others with similar experiences. Their need
of togetherness was fulfilled at the association and they described being
strengthened by the support received. Because of the lack of information and
knowledge about FM, the association was described as an important venue for
getting and mediating information about the illness. CONCLUSIONS: At the
association the women seem to be empowered, which increases their ability to
manage their daily lives despite the limitations imposed by FM. Healthcare
personnel could not satisfy the women's needs and to manage to support women with
FM. There is a need for communication based on a shared understanding between the
women and healthcare personnel. IMPLICATIONS FOR REHABILITATION: This study
highlighted the need for communication based on a shared understanding between
people with chronic illness and healthcare personnel to support and strengthen
women with FM in their daily lives. The FM associations meet the needs for
togetherness, confirmation, and information that the women with FM in this study
described and healthcare personnel could not satisfy. Healthcare personnel can
learn from FM associations how to empower women with FM in their everyday lives.
PMID- 24350658
TI - The influence of foetal prednisone exposure on the cortisol levels in the
offspring.
AB - OBJECTIVE: Pregnant women suffering from autoimmune disease use glucocorticoids.
Glucocorticoids can partly diffuse to the foetus and may influence the
development of the foetal hypothalamic-pituitary-adrenal axis, especially in
early stage of pregnancy. The objective was to investigate whether prednisone
exposure in utero influences the cortisol levels of the prepubertal children.
DESIGN: Mothers participated in a prospective cohort study on rheumatoid
arthritis (RA) and pregnancy. Children were exposed (n = 44) or nonexposed (n =
65) to prednisone in utero. Salivary cortisol levels were taken from all children
during 1 day: at awakening, 30 min after awakening, 1 p.m. and bedtime. Cortisol
levels between groups were also analysed using area under the curve (AUC),
cortisol awakening response (CAR) and slope. RESULTS: The mean age (SD) of the
children was 6.98 (1.23). The difference in mean (SD) cortisol level at '1 p.m.'
was 5.42 nm (4.08) in the prednisone-exposed and 3.97 nm (4.00) in the nonexposed
(P = 0.03). Prednisone-exposed children had a higher AUC (beta = 13.28; P =
0.02), even after correction for RA disease activity. No differences were found
on CAR, slope or blood pressure. The cortisol levels of the nonexposed were more
similar to the age-specific references than the prednisone-exposed. CONCLUSION:
Prednisone use during pregnancy is associated with a higher daytime cortisol
level, in the prepubertal offspring, not yet accompanied with clinical outcomes.
This conclusion will have no consequences at this moment, but it does raise
questions concerning prednisone exposure in utero and the long-term consequences
for the offspring.
PMID- 24350659
TI - A 23Na magic angle spinning nuclear magnetic resonance, XANES, and high
temperature X-ray diffraction study of NaUO3, Na4UO5, and Na2U2O7.
AB - The valence state of uranium has been confirmed for the three sodium uranates
NaU(V)O3/[Rn](5f(1)), Na4U(VI)O5/[Rn](5f(0)), and Na2U(VI)2O7/[Rn](5f(0)), using
X-ray absorption near-edge structure (XANES) spectroscopy. Solid-state (23)Na
magic angle spinning nuclear magnetic resonance (MAS NMR) measurements have been
performed for the first time, yielding chemical shifts at -29.1 (NaUO3), 15.1
(Na4UO5), and -14.1 and -19 ppm (Na1 8-fold coordinated and Na2 7-fold
coordinated in Na2U2O7), respectively. The [Rn]5f(1) electronic structure of
uranium in NaUO3 causes a paramagnetic shift in comparison to Na4UO5 and Na2U2O7,
where the electronic structure is [Rn]5f(0). A (23)Na multi quantum magic angle
spinning (MQMAS) study on Na2U2O7 has confirmed a monoclinic rather than
rhombohedral structure with evidence for two distinct Na sites. DFT calculations
of the NMR parameters on the nonmagnetic compounds Na4UO5 and Na2U2O7 have
permitted the differentiation between the two Na sites of the Na2U2O7 structure.
The linear thermal expansion coefficients of all three compounds have been
determined using high-temperature X-ray diffraction: alphaa = 22.7 * 10(-6) K(
1), alphab = 12.9 * 10(-6) K(-1), alphac = 16.2 * 10(-6) K(-1), and alphavol =
52.8 * 10(-6) K(-1) for NaUO3 in the range 298-1273 K; alphaa = 37.1 * 10(-6) K(
1), alphac = 6.2 * 10(-6) K(-1), and alphavol = 81.8 * 10(-6) K(-1) for Na4UO5 in
the range 298-1073 K; alphaa = 6.7 * 10(-6) K(-1), alphab = 14.4 * 10(-6) K(-1),
alphac = 26.8 * 10(-6) K(-1), alphabeta = -7.8 * 10(-6) K(-1), and alphavol =
217.6 * 10(-6) K(-1) for Na2U2O7 in the range 298-573 K. The alpha to beta phase
transition reported for the last compound above about 600 K was not observed in
the present studies, either by high-temperature X-ray diffraction or by
differential scanning calorimetry.
PMID- 24350660
TI - Immediate placement and restoration of dental implants in the esthetic region:
clinical case series.
AB - AIM: The objective of this study was to assess the hard and soft tissue changes
following immediate placement and provisional restoration of single-tooth
implants in the aesthetic zone. METHODS: Thirteen patients with immediately
placed and restored implants were included in this study. All participating
patients underwent the same treatment strategy that involved removal of the
failed tooth, flapless surgery, immediate implant placement, and connection of a
screw-retained provisional restoration. Three months following implant placement,
the temporary crowns were replaced by the definitive restorations. Implant
survival rates, and hard and soft tissue changes were measured using periapical X
rays and photographs. The range of the observation period was between 12 and 37
months with a mean period of 23.2 +/- 7.6 months. RESULTS: At the time of follow
up, all implants were present with no complications. Radiographic evaluation
revealed a mean mesial bone gain of 1.20 +/- 1.01 mm and a mean distal bone gain
of 0.80 +/- 1.14 mm, which reached statistical significance. The mean mid-buccal
recession was 0.20 +/- 0.78 mm, whereas the mesial and distal papillae height
loss was 0.50 +/- 1.26 mm and 0.30 +/- 0.82 mm, respectively. The changes in the
soft tissues did not reach statistical significance. CONCLUSION: Notwithstanding
the limitation of a small sample size, this study shows that immediate implant
placement and provisional restoration in the maxillary aesthetic zone can result
in favorable treatment outcomes with regards to soft and hard tissues changes
over a follow-up period of 23.2 +/- 7.6 months. CLINICAL SIGNIFICANCE: Most
clinical trials investigating immediate implant placement and immediate
restoration in the maxillary anterior zone have focused on implant survival and
implant success, with particular emphasis on radiographically assessed hard
tissues changes. However, this study assesses the soft tissue changes associated
with this procedure, which is an important area of study given the esthetic
demands of implant therapy in the maxillary anterior region.
PMID- 24350661
TI - What is and what could have been: experiencing regret and relief across
childhood.
AB - Counterfactual emotions, such as regret and relief, are considered important in
daily-life choice behaviour, learning and emotion regulation. A prominent
question is from which age counterfactual emotions develop. In this study, we
compared a more "traditional" analysis with a latent-class analysis (LCA) that
allows the study of individual differences and a more detailed assessment of
counterfactual emotions. Four groups of children (5-6 years, 7-8 years, 9-10
years and 11-13 years) and a group of young adults performed a choice task in
which they encountered a Regret situation (chosen option was worse than
alternative), a Relief situation (chosen option was better than alternative) and
a Baseline situation (chosen option was equal to alternative). Traditional
analyses indicated regret and relief to be present from ages 7 to 8. In contrast,
the LCA indicated that subgroups experiencing regret and relief were present in
all age groups, although regret and relief subgroups increased with age.
Moreover, analyses indicated that higher reasoning scores increased the
probability to belong to regret and relief subgroups and that the experience of
regret dependent on trial order, being more prominent in later trials. We
conclude that an individual-difference approach can advance insight into
emotional development.
PMID- 24350663
TI - Noncovalent interactions in microsolvated networks of trimethylamine N-oxide.
AB - The effects of the formation of hydrogen-bonded networks on the important
osmolyte trimethylamine N-oxide (TMAO) are explored in a joint Raman
spectroscopic and electronic structure theory study. Spectral shifts in the
experimental Raman spectra of TMAO and deuterated TMAO microsolvated with water,
methanol, ethanol, and ethylene glycol are compared with the results of
electronic structure calculations on explicit hydrogen-bonded molecular clusters.
Very good agreement between experiment and theory suggests that it is the local
hydrogen-bonded geometry at TMAO's oxygen atom that dominates the structure of
the extended hydrogen-bonded networks and that TMAO's unique stabilizing
abilities are a result of the "indirect effect" model. Natural bonding orbital
(NBO) calculations further reveal that hyperconjugation results in vibrational
blue shifts in TMAO's C-H stretching region when solvated and a red shift in
methanol's C-H stretching region when hydrogen bonding with TMAO.
PMID- 24350664
TI - Improving immunization data management: an editorial on the potential of
Electronic Health Records.
AB - Immunizations are critical for maintaining individual and population health. Yet
ensuring that complete immunization histories are available at the point of care
is challenging. Currently, immunization information systems (IIS) are used to
aggregate data at a regional level, although their value is often limited by
incomplete data. The Electronic Health Record (EHR) Incentive Program, which is
an unprecedented federal initiative promoting EHR use, is linking financial
payments in part to demonstrating ability to transmit EHR data directly to IIS
and thus has potential to change immunization data management on a large scale.
We believe that EHRs are critical for allowing more complete and timely
immunization data capture and will offer many benefits. To achieve these
benefits, however, it will be necessary to engage the EHR vendor community in
developing EHRs that allow for comprehensive immunization data capture and policy
makers to incentivize bidirectional, real-time exchange between IIS and EHRs.
PMID- 24350662
TI - Efficacy and safety of once-daily oxybutynin patch versus placebo and propiverine
in Japanese patients with overactive bladder: A randomized double-blind trial.
AB - OBJECTIVES: To evaluate the efficacy and safety of once-daily oxybutynin patch
therapy for overactive bladder. METHODS: A randomized double-blind trial was
carried out in patients with overactive bladder syndrome, who received an
oxybutynin patch, propiverine (20 mg) or placebo once daily for 12 weeks. The
primary efficacy end-point was the change of the mean daily number of
micturitions in week 12. RESULTS: A total of 1530 patients were randomized to
receive the oxybutynin patch (573), propiverine (576) or placebo (381). The
change of the mean daily frequency of micturition from baseline in the full
analysis set was -1.89 +/- 2.04 with the oxybutynin patch, which was
significantly higher than with placebo (-1.44 +/- 2.23) (P = 0.0015). The
difference of the mean change in the mean daily number of micturitions between
the oxybutynin patch and propiverine groups showed a 95% confidence interval of
0.28 to 0.21, and the upper limit of this interval was below the predefined non
inferiority margin of 0.37, showing non-inferiority of the oxybutynin patch to
propiverine. The incidence of dry mouth and constipation was higher with
propiverine than with the oxybutynin patch or placebo. Application site
dermatitis was more frequent with the oxybutynin patch (31.8%) than with
propiverine (5.9%) or placebo (5.2%), but the dermatitis was generally mild.
CONCLUSION: This trial shows the efficacy of the new once-daily oxybutynin patch
for overactive bladder. Despite a higher rate of dermatitis with the oxybutynin
patch, dry mouth and constipation occurs less often than during treatment with
propiverine.
PMID- 24350665
TI - Lung mesenchymal stromal cells in development and disease: to serve and protect?
AB - SIGNIFICANCE: Bronchopulmonary dysplasia (BPD) is a disease of the developing
lung that afflicts extreme preterm infants in the neonatal intensive care unit.
Follow-up studies into adulthood show that BPD is not merely a problem of the
neonatal period, as it also may predispose to early-onset emphysema and poor lung
function in later life. RECENT ADVANCES: The increasing promise of bone marrow-
or umbilical cord-derived mesenchymal stromal cells (MSCs) to repair neonatal and
adult lung diseases may for the first time offer the chance to make substantial
strides in improving the outcome of extreme premature infants at risk of
developing BPD. As more knowledge has been obtained on MSCs over the past
decades, it has become clear that each organ has its own reservoir of endogenous
MSCs, including the lung. CRITICAL ISSUES: We have only barely scratched the
surface on what resident lung MSCs exactly are and what their role and function
in lung development may be. Moreover, what happens to these putative repair cells
in BPD when alveolar development goes awry and why do their counterparts from the
bone marrow and umbilical cord succeed in restoring normal alveolar development
when they themselves do not? FUTURE DIRECTIONS: Much work remains to be carried
out to validate lung MSCs, but with the high potential of MSC-based treatment for
BPD and other lung diseases, a thorough understanding of the endogenous lung MSC
will be pivotal to get to the bottom of these diseases.
PMID- 24350666
TI - Enantioselective alkylation by binaphthyl chiral phase-transfer catalysts: a DFT
based conformational analysis.
AB - A conformational search method based on the density functional theory (DFT) was
successfully applied to explore a mechanism for the highly enantioselective
alkylation by binaphthyl-modifed chiral phase-transfer catalysts. Key
interactions that govern the enantioselectivity were analyzed. The computational
results are encouraging for further application of the DFT-based conformational
search toward the rational design of next-generation asymmetric phase transfer
catalysts.
PMID- 24350667
TI - Catalytic reduction of N2 to NH3 by an Fe-N2 complex featuring a C-atom anchor.
AB - While recent spectroscopic studies have established the presence of an
interstitial carbon atom at the center of the iron-molybdenum cofactor (FeMoco)
of MoFe-nitrogenase, its role is unknown. We have pursued Fe-N2 model chemistry
to explore a hypothesis whereby this C-atom (previously denoted as a light X
atom) may provide a flexible trans interaction with an Fe center to expose an Fe
N2 binding site. In this context, we now report on Fe complexes of a new
tris(phosphino)alkyl (CP(iPr)3) ligand featuring an axial carbon donor. It is
established that the iron center in this scaffold binds dinitrogen trans to the
C(alkyl)-atom anchor in three distinct and structurally characterized oxidation
states. Fe-C(alkyl) lengthening is observed upon reduction, reflective of
significant ionic character in the Fe-C(alkyl) interaction. The anionic
(CP(iPr)3)FeN2(-) species can be functionalized by a silyl electrophile to
generate (CP(iPr)3)Fe-N2SiR3. (CP(iPr)3)FeN2(-) also functions as a modest
catalyst for the reduction of N2 to NH3 when supplied with electrons and protons
at -78 degrees C under 1 atm N2 (4.6 equiv NH3/Fe).
PMID- 24350668
TI - Estimating nanoparticle optical absorption with magnetic resonance temperature
imaging and bioheat transfer simulation.
AB - PURPOSE: Optically activated nanoparticle-mediated heating for thermal therapy
applications is an area of intense research. The ability to characterise the
spatio-temporal heating potential of these particles for use in modelling under
various exposure conditions can aid in the exploration of new approaches for
therapy as well as more quantitative prospective approaches to treatment
planning. The purpose of this research was to investigate an inverse solution to
the heat equation using magnetic resonance temperature imaging (MRTI) feedback,
for providing optical characterisation of two types of nanoparticles (gold-silica
nanoshells and gold nanorods). METHODS: The optical absorption of homogeneous
nanoparticle-agar mixtures was measured during exposure to an 808 nm laser using
real-time MRTI. A coupled finite element solution of heat transfer was registered
with the data and used to solve the inverse problem. The L2 norm of the
difference between the temperature increase in the model and MRTI was minimised
using a pattern search algorithm by varying the absorption coefficient of the
mixture. RESULTS: Absorption fractions were within 10% of literature values for
similar nanoparticles. Comparison of temporal and spatial profiles demonstrated
good qualitative agreement between the model and the MRTI. The weighted root mean
square error was <1.5 sigmaMRTI and the average Dice similarity coefficient for
DeltaT = 5 degrees C isotherms was >0.9 over the measured time interval.
CONCLUSION: This research demonstrates the feasibility of using an indirect
method for making minimally invasive estimates of nanoparticle absorption that
might be expanded to analyse a variety of geometries and particles of interest.
PMID- 24350670
TI - Plasmodium vivax malaria incidence over time and its association with temperature
and rainfall in four counties of Yunnan Province, China.
AB - BACKGROUND: Transmission of Plasmodium vivax malaria is dependent on vector
availability, biting rates and parasite development. In turn, each of these is
influenced by climatic conditions. Correlations have previously been detected
between seasonal rainfall, temperature and malaria incidence patterns in various
settings. An understanding of seasonal patterns of malaria, and their weather
drivers, can provide vital information for control and elimination activities.
This research aimed to describe temporal patterns in malaria, rainfall and
temperature, and to examine the relationships between these variables within four
counties of Yunnan Province, China. METHODS: Plasmodium vivax malaria
surveillance data (1991-2006), and average monthly temperature and rainfall were
acquired. Seasonal trend decomposition was used to examine secular trends and
seasonal patterns in malaria. Distributed lag non-linear models were used to
estimate the weather drivers of malaria seasonality, including the lag periods
between weather conditions and malaria incidence. RESULTS: There was a declining
trend in malaria incidence in all four counties. Increasing temperature resulted
in increased malaria risk in all four areas and increasing rainfall resulted in
increased malaria risk in one area and decreased malaria risk in one area. The
lag times for these associations varied between areas. CONCLUSIONS: The
differences detected between the four counties highlight the need for local
understanding of seasonal patterns of malaria and its climatic drivers.
PMID- 24350671
TI - Stud identity among female-born youth of color: joint conceptualizations of
gender variance and same-sex sexuality.
AB - Little is known about the experiences of individuals who may fall under the
umbrella of "transgender" but do not transition medically and/or socially. The
impact of the increasingly widespread use of the term "transgender" itself also
remains unclear. The authors present narratives from four female-born youth of
color who report a history of identifying as a "stud." Through analysis of their
processes of identity signification, the authors demonstrate how stud identity
fuses aspects of gender and sexuality while providing an alternate way of making
meaning of gender variance. As such, this identity has important implications for
research and organizing centered on an LGBT-based identity framework.
PMID- 24350669
TI - Loss of IP3 receptor function in neuropeptide secreting neurons leads to obesity
in adult Drosophila.
AB - BACKGROUND: Intracellular calcium signaling regulates a variety of cellular and
physiological processes. The inositol 1,4,5 trisphosphate receptor (IP3R) is a
ligand gated calcium channel present on the membranes of endoplasmic reticular
stores. In previous work we have shown that Drosophila mutants for the IP3R
(itprku) become unnaturally obese as adults with excessive storage of lipids on a
normal diet. While the phenotype manifests in cells of the fat body, genetic
studies suggest dysregulation of a neurohormonal axis. RESULTS: We show that
knockdown of the IP3R, either in all neurons or in peptidergic neurons alone,
mimics known itpr mutant phenotypes. The peptidergic neuron domain includes, but
is not restricted to, the medial neurosecretory cells as well as the
stomatogastric nervous system. Conversely, expression of an itpr+ cDNA in the
same set of peptidergic neurons rescues metabolic defects of itprku mutants.
Transcript levels of a gene encoding a gastric lipase CG5932 (magro), which is
known to regulate triacylglyceride storage, can be regulated by itpr knockdown
and over-expression in peptidergic neurons. Thus, the focus of observed itpr
mutant phenotypes of starvation resistance, increased body weight, elevated lipid
storage and hyperphagia derive primarily from peptidergic neurons. CONCLUSIONS:
The present study shows that itpr function in peptidergic neurons is not only
necessary but also sufficient for maintaining normal lipid metabolism in
Drosophila. Our results suggest that intracellular calcium signaling in
peptidergic neurons affects lipid metabolism by both cell autonomous and non
autonomous mechanisms.
PMID- 24350672
TI - A research agenda for documenting disability status within healthcare
organizations to address disparities in care.
AB - Individuals with disabilities are at a greater risk of experiencing healthcare
disparities. To address these disparities, healthcare organizations (HCOs) need
to consistently and accurately document patients' disability status.
Unfortunately, the evidence base does not yet exist to guide HCOs in determining
what data to collect or the best method to collect the data. The authors propose
a research agenda for developing and administering disability status questions.
To determine what data to collect, researchers need to addresses the following
challenges: disability is a complex concept, a wide range of types of
disabilities exists, severity levels of disability can differ and, finally,
patients might use assistive devices or aids to mitigate or ameliorate their
disability. Additionally, research is needed to determine the frequency with
which to administer questions due to the dynamic nature of disability, and to
develop protocols for assessing the most appropriate person to answer disability
status questions. Targeted research will lead to disability status questions that
accurately and consistently identify individuals with disabilities and produce
actionable data that HCOs can use to detect and address potential disparities in
care.
PMID- 24350673
TI - Small bright charged colloidal quantum dots.
AB - Using electrochemical charge injection, the fluorescence lifetimes of negatively
charged core/shell CdTe/CdSe QDs are measured as a function of core size and
shell thickness. It is found that the ensemble negative trion lifetimes reach a
maximum (~4.5 ns) for an intermediate shell thickness. This leads to the smallest
particles (~4.5 nm) with the brightest trion to date. Single dot measurements
show that the negative charge suppresses blinking and that the trion can be as
bright as the exciton at room temperature. In contrast, the biexciton lifetimes
remain short and exhibit only a monotonous increase with shell thickness, showing
no correlation with the negative trion decays. The suppression of the Auger
process in small negatively charged CdTe/CdSe quantum dots is unprecedented and a
significant departure from prior results with ultrathick CdSe/CdS core/shell or
dot-in-rod structures. The proposed reason for the optimum shell thickness is
that the electron-hole overlap is restricted to the CdTe core while the electron
is tuned to have zero kinetic energy in the core for that optimum shell
thickness. The different trend of the biexciton lifetime is not explained but
tentatively attributed to shorter-lived positive trions at smaller sizes. These
results improve our understanding of multiexciton recombination in colloidal
quantum dots and may lead to the design of bright charged QDs for more efficient
light-emitting devices.
PMID- 24350674
TI - Simultaneous determination of selected biogenic amines in alcoholic beverage
samples by isotachophoretic and chromatographic methods.
AB - A simple and useful method for the determination of biogenic amines in beverage
samples based on isotachophoretic separation is described. The proposed procedure
permitted simultaneous analysis of histamine, tyramine, cadaverine, putrescine,
tryptamine, 2-phenylethylamine, spermine and spermidine. The data presented
demonstrate the utility, simplicity, flexibility, sensitivity and environmentally
friendly character of the proposed method. The precision of the method expressed
as coefficient of variations varied from 0.1% to 5.9% for beverage samples,
whereas recoveries varied from 91% to 101%. The results for the determination of
biogenic amines were compared with an HPLC procedure based on a pre-column
derivatisation reaction of biogenic amines with dansyl chloride. Furthermore, the
derivatisation procedure was optimised by verification of concentration and pH of
the buffer, the addition of organic solvents, reaction time and temperature.
PMID- 24350675
TI - Resistant bipolar depressive disorder: case analysis of adjunctive transcranial
magnetic stimulation efficiency in medical comorbid conditions.
PMID- 24350676
TI - Fish oil, contained in eicosapentaenoic acid and docosahexaenoic acid, attenuates
testicular and spermatological damage induced by cisplatin in rats.
AB - The aim of this study was to investigate the beneficial effects of the fish oil
(FO) supplementation on oxidative stress, sperm characteristics and histological
alterations in the male reproductive system of rats against cisplatin (CP)
toxicity. The rats were divided randomly into 4 equal groups (control, FO, CP and
FO + CP). FO was orally administered at the dose of 1 softgel per rat per day for
14 days and CP was intraperitoneally given at the dose of 7 mg kg(-1) with a
single injection. In CP + FO group, they were applicated at the same doses and
times. The results showed that CP caused a significant oxidative damage via
induction of lipid peroxidation and reduction in the antioxidant defence system
potency in the testis tissue. In addition, sperm motility and sperm concentration
significantly decreased but the abnormal sperm rate and histopathological
testicular damage increased with CP treatment. On the other hand, FO treatment
prevented oxidative, histopathological and spermatological effects of CP and
reversed side effects of CP. In conclusion, FO supplementation had significant
beneficial effects against CP toxicity on male reproductive system and toxic
effects of CP can be prevented by FO treatment. Therefore, it appears that fish
oil may be useful for the prevention and treatment of cisplatin-induced
reproductive system toxicity.
PMID- 24350677
TI - Bayesian model selection in complex linear systems, as illustrated in genetic
association studies.
AB - Motivated by examples from genetic association studies, this article considers
the model selection problem in a general complex linear model system and in a
Bayesian framework. We discuss formulating model selection problems and
incorporating context-dependent a priori information through different levels of
prior specifications. We also derive analytic Bayes factors and their
approximations to facilitate model selection and discuss their theoretical and
computational properties. We demonstrate our Bayesian approach based on an
implemented Markov Chain Monte Carlo (MCMC) algorithm in simulations and a real
data application of mapping tissue-specific eQTLs. Our novel results on Bayes
factors provide a general framework to perform efficient model comparisons in
complex linear model systems.
PMID- 24350678
TI - Detecting cellular reprogramming determinants by differential stability analysis
of gene regulatory networks.
AB - BACKGROUND: Cellular differentiation and reprogramming are processes that are
carefully orchestrated by the activation and repression of specific sets of
genes. An increasing amount of experimental results show that despite the large
number of genes participating in transcriptional programs of cellular phenotypes,
only few key genes, which are coined here as reprogramming determinants, are
required to be directly perturbed in order to induce cellular reprogramming.
However, identification of reprogramming determinants still remains a
combinatorial problem, and the state-of-art methods addressing this issue rests
on exhaustive experimentation or prior knowledge to narrow down the list of
candidates. RESULTS: Here we present a computational method, without any
preliminary selection of candidate genes, to identify reduced subsets of genes,
which when perturbed can induce transitions between cellular phenotypes. The
method relies on the expression profiles of two stable cellular phenotypes along
with a topological analysis stability elements in the gene regulatory network
that are necessary to cause this multi-stability. Since stable cellular
phenotypes can be considered as attractors of gene regulatory networks, cell fate
and cellular reprogramming involves transition between these attractors, and
therefore current method searches for combinations of genes that are able to
destabilize a specific initial attractor and stabilize the final one in response
to the appropriate perturbations. CONCLUSIONS: The method presented here
represents a useful framework to assist researchers in the field of cellular
reprogramming to design experimental strategies with potential applications in
the regenerative medicine and disease modelling.
PMID- 24350679
TI - Mechanisms of biotic resistance across complex life cycles.
AB - Biotic resistance is the ability of communities to inhibit the establishment,
spread or impact of novel species. However, the interactions that underlie biotic
resistance depend heavily on the contexts in which species interact.
Consequently, studies of biotic resistance that consider single processes,
patches, species or life-history stages may provide an incomplete picture of the
capacity for communities to resist invasion. Many organisms have multiphasic life
cycles, where individuals can occupy distinct niches at different stages of the
life history. Generally, studies of biotic resistance focus on interactions
within a single life-history stage, and interactions at other life-history stages
are overlooked. Here, we demonstrate that different mechanisms of biotic
resistance occur across the life history and together limit the invasion success
of an introduced marine invertebrate (Ciona intestinalis) in Northern California.
We tested the role of interactions (competition and predation) with the resident
community in limiting the abundance of Ciona through experiments conducted on
fertilization, larval survival, settlement, early postsettlement survival, and
the survival of juveniles and adults. Under some circumstances, Ciona became
abundant in mid-successional stages and showed more rapid growth rates than a
morphologically similar native species, Ascidia ceratodes. However, predators
reduced Ciona abundance much more than that of Ascidia at several life stages.
Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early
life-history interactions with other sessile species at the fertilization, larval
and recruit stages had modest to no effects on Ciona abundance. The presence of
biotic resistance mechanisms acting at multiple life stages, and potentially
under different conditions, suggests that different components of biotic
resistance interact to enhance the resident community's resistance to invasion.
PMID- 24350680
TI - Analysis of covalent modifications of proteins by oxidized phospholipids using a
novel method of peptide enrichment.
AB - Free radical-induced oxidation of phospholipids contributes significantly to
pathologies associated with inflammation and oxidative stress. Detection of
covalent interaction between oxidized phospholipids (oxPL) and proteins by LC
MS/MS could provide valuable information about the molecular mechanisms of oxPL
effects. However, such studies are very limited because of significant challenges
in detection of the comparatively low levels of oxPL-protein adducts in complex
biological systems. Current approaches have several limitations, most important
of which is the inability to detect protein modifications by naturally occurring
oxPL. We now report, for the first time, an enrichment method that can be applied
to the global analysis of protein adducts with various naturally occurring oxPL
in relevant biological systems. This method exploits intrinsic properties of
peptides modified by oxPL, allowing highly efficient enrichment of oxPL-modified
peptides from biological samples. Very low levels of oxPL-protein adducts (<2
ppm) were detected using this enrichment method in combination with LC-MS/MS. We
applied the method to several model systems, including oxidation of high density
lipoprotein (HDL) and interaction of human platelets with a specific oxPL, and
demonstrated its extremely high efficiency and productivity. We report multiple
new modifications of apolipoproteins in HDL and proteins in human platelets.
PMID- 24350681
TI - Remestemcel-L for acute graft-versus-host disease therapy.
AB - INTRODUCTION: Remestemcel-L (Prochymal(r), Osiris) is an off-the-shelf adult
mesenchymal stromal cell product that has been applied to acute graft-versus-host
disease (aGvHD) for its immunomodulatory properties. AREAS COVERED: This article
discusses preclinical and clinical studies supporting the use of remestemcel-L in
aGvHD as well as the current regulatory status. This information was based upon a
PubMed and Internet search. EXPERT OPINION: Phase II studies suggest remestemcel
L may have clinical activity in aGvHD and confirm tolerability. However, these
results must be interpreted cautiously with any use of remestemcel-L optimally
occurring in the context of a clinical trial. Further clarity will be obtained
when the results of a completed Phase III study are published. There is a small
market for remestemcel-L in aGvHD. A possible future scenario is that a more
prevalent indication is found and remestemcel-L is approved for that indication,
but use continues for aGvHD.
PMID- 24350682
TI - Consistency of safety profile of new oral anticoagulants in patients with renal
failure.
AB - BACKGROUND: The use of new oral anticoagulants (NOACs) in patients with impaired
renal function has raised major concerns, in particular the possibility of an
increased risk of bleeding due to accumulation. The aims of this work were to
assess the safety of NOACs in patients with renal failure and describe the
relationship between clinical events and drug renal excretion magnitude. METHODS:
All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in
patients with estimated glomerular filtration (eGFR) rate < 50 mL min(-1) were
eligible. The main safety and efficacy outcomes were major bleeding and
thrombosis. A meta-regression was performed to estimate the correlation between
the treatment effect estimate and the percentage of renal excretion. RESULTS:
Nine studies (12 272 patients) were included. A significantly greater relative
reduction in major bleeding was seen for NOACs with renal excretion <50% (RR,
0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85
1.07) (interaction test, P < 0.0001). A linear relationship between the relative
risk of major bleeding and the magnitude of renal excretion was found by meta
regression (R(2) = 0.66, P = 0.03). For thrombosis, a greater treatment effect
of NOA vs. INR-adjusted VKA was observed in patients with eGFR < 50 mL min(-1)
(RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal
excretion was found. CONCLUSIONS: New oral anticoagulants were at least as
effective as VKAs, with reduced risks of major bleeding and thrombosis in
patients with eGFR < 50 mL min(-1) . The renal excretion of these new drugs
seemed to modify the safety profile, contrary to the efficacy.
PMID- 24350683
TI - Open pentameric calixarene nanocage.
AB - A novel open helmetlike coordination cage has been synthesized based on Co4
calixarene shuttlecock-like secondary building units and in situ generated
phosphate anions, where the opening of the cage comprises a large 16-membered
ring. The above unprecedented Co20 nanocage presents the first pentameric
calixarene coordination compound. Sorption behavior and magnetic properties are
also investigated.
PMID- 24350684
TI - Editorial comment from Dr Karatag et al. to tubeless simultaneous bilateral
percutaneous nephrolithotomy: safety, feasibility and efficacy in an Indian
setting.
PMID- 24350685
TI - Synthesis of uranium-ligand multiple bonds by cleavage of a trityl protecting
group.
AB - Addition of KSCPh3 to [U(NR2)3] (R = SiMe3) in tetrahydrofuran, followed by
addition of 18-crown-6, results in formation of the U(IV) sulfide, [K(18-crown
6)][U(S)(NR2)3] (1) and Gomberg's dimer. Similarly, addition of KOCPh3 to
[U(NR2)3] in tetrahydrofuran, followed by addition of 18-crown-6, results in
formation of the U(IV) oxide, [K(18-crown-6)][U(O)(NR2)3] (3). Also observed in
this transformation are the triphenylmethyl anion, [K(18-crown-6)(THF)2][CPh3]
(5), and the U(IV) alkoxide, [U(OCPh3)(NR2)3] (4).
PMID- 24350687
TI - Live attenuated vaccine: the first clinically approved dengue vaccine?
AB - Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen in
humans. There are 390 million human infections each year, with 96 million
infections exhibiting disease symptoms. Currently, there is no clinically
approved vaccine and antiviral for DENV. The four serotypes of DENV (DENV-1, -2,
3 and -4) have 25-40% variation at the amino acid level. Such variation has posed
challenges for the development of a tetravalent vaccine and therapeutics.
PMID- 24350686
TI - Coarse-grained models for aqueous polyethylene glycol solutions.
AB - A new coarse-grained force field is developed for polyethylene glycol (PEG) in
water. The force field is based on the MARTINI model but with the big multipole
water (BMW) model for the solvent. The polymer force field is reparameterized
using the MARTINI protocol. The new force field removes the ring-like
conformations seen in simulations of short chains with the MARTINI force field;
these conformations are not observed in atomistic simulations. We also
investigate the effect of using parameters for the end-group that are different
from those for the repeat units, with the MARTINI and BMW/MARTINI models. We find
that the new BMW/MARTINI force field removes the ring-like conformations seen in
the MARTINI models and has more accurate predictions for the density of neat PEG.
However, solvent-separated-pairs between chain ends and slow dynamics of the PEG
reflect its own artifacts. We also carry out fine-grained simulations of PEG with
bundled water clusters and show that the water bundling can lead to ring-like
conformations of the polymer molecules. The simulations emphasize the pitfalls of
coarse-graining several molecules into one site and suggest that polymer-solvent
systems might be a stringent test for coarse-grained force fields.
PMID- 24350688
TI - Intrathecal baclofen associated with improvement of consciousness disorders in
spasticity patients.
AB - OBJECTIVE: Intrathecal baclofen (ITB) pump is a therapeutic option for persistent
vegetative state and minimal conscious state patients that have associated
spasticity. We investigated whether this treatment modality can affect their
level of consciousness. METHOD: In this prospective, open label, observational
study, we implanted ITB pumps for the treatment of spasticity in eight patients
with disorders of consciousness (vegetative state and minimally conscious state)
and we followed them with the Coma Recovery Scale-Revised, the Eastern
Cooperative Oncology Group (ECOG) performance scale, and the Modified Ashworth
spasticity scale. Baclofen dose and complications also were noted. RESULTS: The
offending pathologies were traumatic brain injury in six, anoxia due to cardiac
arrest in one, acute obstructive hydrocephalus in one. Two of the patients showed
a marked, persistent improvement that fulfilled the criteria of emergence from
minimally conscious state. Two of patients had their ITB pumps prematurely
removed because of complications. The ECOG score was 4 for all patients and did
not change during the study. CONCLUSION: ITB might be associated with a
significant improvement in the disorder of consciousness of two patients from a
total of six that had a chronic ITB treatment.
PMID- 24350689
TI - Genetic variation in scaly hair-fin anchovy Setipinna tenuifilis (Engraulididae)
based on the mitochondrial DNA control region.
AB - Scaly hair-fin anchovy (Setipinna tenuifilis) is a small, pelagic and economical
species and widely distributed in Chinese coastal water. However, resources of S.
tenuifilis have been reduced due to overfishing. For better fishery management,
it is necessary to understand the pattern of S. tenuifilis's biogeography.
Genetic analyses were taken place to detect their population genetic variation. A
total of 153 individuals from 7 locations (Dongying, Yantai, Qingdao, Nantong,
Wenzhou, Xiamen and Beibu Bay) were sequenced at the 5' end of mtDNA control
region. A 39-bp tandem repeated sequence was found at the 5' end of the segment
and a polymorphism of tandem repeated sequence was detected among 7 populations.
Both mismatch distribution analysis and neutrality tests showed S. tenuifilis had
experienced a recent population expansion. The topology of neighbor-joining tree
and Bayesian evolutionary tree showed no significant genealogical branches or
clusters of samples corresponding to sampling locality. Hierarchical analysis of
molecular variance and conventional pairwise population Fst value at group
hierarchical level implied that there might have genetic divergence between
southern group (population WZ, XM and BB) and northern group (population DY, YT,
QD and NT). We concluded that there might have three different fishery management
groups of S. tenuifilis and the late Pleistocene glacial event might have a
crucial effect on present-day demography of S. tenuifilis in this region.
PMID- 24350690
TI - When expectation meets experience: parents' recollections of and experiences with
a child diagnosed with hearing loss soon after birth.
AB - OBJECTIVE: To examine parents' recollections of and their experiences with
bringing up a child diagnosed with hearing loss at a very young age. DESIGN:
Based on the analysis of informal parent discussion groups, four open-ended
questions were formulated to solicit information about parents' expectations
following diagnosis, as well as experiences and challenges when raising a child
with a hearing loss. STUDY SAMPLE: Forty parents of children, aged between three
to five years, who were diagnosed with hearing loss before the age of three
years. RESULTS: Parents' responses revealed strong support for early
intervention, high expectations for their child's development, and desire for
information tailored to individual needs. Parents also reported anxiety relating
to their perceptions of the significance of consistent device usage on their
child's development. Further concerns arose from their observations of the
difficulties experienced by their child in real-world environments despite
consistent device usage, and their perception of their child's language delay
despite early intervention. CONCLUSIONS: The findings point to a need to support
parents to form realistic expectations based on current knowledge. Implications
for clinicians to provide improved management of children with hearing loss are
discussed.
PMID- 24350691
TI - Longitudinal outcomes of children with hearing impairment (LOCHI).
PMID- 24350692
TI - A comparison of NAL and DSL prescriptive methods for paediatric hearing-aid
fitting: predicted speech intelligibility and loudness.
AB - OBJECTIVE: To examine the impact of prescription on predicted speech
intelligibility and loudness for children. DESIGN: A between-group comparison of
speech intelligibility index (SII) and loudness, based on hearing aids fitted
according to NAL-NL1, DSL v4.1, or DSL m[i/o] prescriptions. A within-group
comparison of gains prescribed by DSL m[i/o] and NAL-NL2 for children in terms of
SII and loudness. STUDY SAMPLE: Participants were 200 children, who were randomly
assigned to first hearing-aid fitting with either NAL-NL1, DSL v4.1, or DSL
m[i/o]. Audiometric data and hearing-aid data at 3 years of age were used.
RESULTS: On average, SII calculated on the basis of hearing-aid gains were higher
for DSL than for NAL-NL1 at low input level, equivalent at medium input level,
and higher for NAL-NL1 than DSL at high input level. Greater loudness was
associated with DSL than with NAL-NL1, across a range of input levels. Comparing
NAL-NL2 and DSL m[i/o] target gains revealed higher SII for the latter at low
input level. SII was higher for NAL-NL2 than for DSL m[i/o] at medium- and high
input levels despite greater loudness for gains prescribed by DSL m[i/o] than by
NAL-NL2. CONCLUSION: The choice of prescription has minimal effects on speech
intelligibility predictions but marked effects on loudness predictions.
PMID- 24350693
TI - Hearing-aid safety: a comparison of estimated threshold shifts for gains
recommended by NAL-NL2 and DSL m[i/o] prescriptions for children.
AB - OBJECTIVE: To investigate the predicted threshold shift associated with the use
of nonlinear hearing aids fitted to the NAL-NL2 or the DSL m[i/o] prescription
for children with the same audiograms. For medium and high input levels, we
asked: (1) How does predicted asymptotic threshold shifts (ATS) differ according
to the choice of prescription? (2) How does predicted ATS vary with hearing level
for gains prescribed by the two prescriptions? DESIGN: A mathematical model
consisting of the modified power law combined with equations for predicting
temporary threshold shift (Macrae, 1994b) was used to predict ATS. STUDY SAMPLE:
Predicted threshold shift were determined for 57 audiograms at medium and high
input levels. RESULTS: For the 57 audiograms, DSL m[i/o] gains for high input
levels were associated with increased risk relative to NAL-NL2. The variation of
ATS with hearing level suggests that NAL-NL2 gains became unsafe when hearing
loss > 90 dB HL. The gains prescribed by DSL m[i/o] became unsafe when hearing
loss > 80 dB HL at a medium input level, and > 70 dB HL at a high input level.
CONCLUSION: There is a risk of damage to hearing for children using nonlinear
amplification. Vigilant checking for threshold shift is recommended.
PMID- 24350694
TI - Introduction to the longitudinal outcomes of children with hearing impairment
(LOCHI) study: background, design, sample characteristics.
AB - OBJECTIVE: This article describes the background and the design of the
longitudinal outcomes of children with hearing impairment (LOCHI) study, and the
characteristics of the study cohort. DESIGN: Children born between 2002 and 2007
who were identified with hearing loss and received audiological intervention by 3
years of age in Australia enrolled in the study. Their demographic
characteristics are described. STUDY SAMPLE: Four hundred and fifty-one children
in New South Wales, Victoria, and Southern Queensland. RESULTS: Data on age at
first hearing-aid fitting for different degrees of hearing loss are reported
together with demographic characteristics of the cohort. CONCLUSION: A unique
environment in Australia where all children with varied access to universal
newborn hearing screening received the same consistent hearing services from a
national hearing service provider makes it possible to investigate the effects of
access to early auditory intervention on children's outcomes at a population
level.
PMID- 24350695
TI - A randomized controlled trial of nonlinear frequency compression versus
conventional processing in hearing aids: speech and language of children at three
years of age.
AB - OBJECTIVE: To determine the effect of nonlinear frequency compression (NLFC) on
children's development of speech and language at three years of age. DESIGN: A
randomized controlled trial was conducted as part of the population-based
longitudinal study on outcomes of children with hearing impairment (LOCHI).
Participants were randomly assigned to fitting with NLFC (Phonak Naida V SP or
UP) or with conventional processing in hearing aids, prescribed by using either
the NAL or the DSL formula. Standardized tests of speech production, receptive
and expressive language were administered, and parent ratings were collected. All
assessments were double-blinded. STUDY SAMPLE: Participants were 44 of the 450
children in the LOCHI cohort. RESULTS: Compared to children using conventional
processing, receptive and expressive language was higher but receptive vocabulary
and consonant articulation scores were lower for children who use NLFC. There was
increased substitution of affricates by fricatives for children using NLFC,
compared to children using conventional amplification. After allowing for the
effect of multiple demographic variables, the difference in global language
scores between groups was not significant (effect: 0.8 [95% confidence interval:
6.7, 8.3]). CONCLUSIONS: There is insufficient evidence to indicate a difference
in language ability between children using NLFC and those using conventional
amplification.
PMID- 24350696
TI - Impact of the presence of auditory neuropathy spectrum disorder (ANSD) on
outcomes of children at three years of age.
AB - OBJECTIVE: To determine the influence of the presence of auditory neuropathy
spectrum disorder (ANSD) on speech, language, and psycho-social development of
children at three years of age. DESIGN: A population-based, longitudinal study
was performed on outcomes of children with hearing impairment (LOCHI) in
Australia. The demographic characteristics of the children were described, and
their developmental outcomes were evaluated at three years of age. Performance of
children with ANSD was compared with that of children without ANSD in the LOCHI
study. STUDY SAMPLE: There were 47 children with ANSD in the study sample.
RESULTS: Sixty-four percent of children with ANSD have hearing sensitivity loss
ranging from mild to severe degree, and the remaining have profound hearing loss.
At three years, 27 children used hearing aids, 19 used cochlear implants, and one
child did not use any hearing device. Thirty percent of children have
disabilities in addition to hearing loss. On average, there were no significant
differences in performance level between children with and without ANSD. Also,
the variability of scores was not significantly different between the two groups.
CONCLUSIONS: There was no significant difference in performance levels or
variability between children with and without ANSD, both for children who use
hearing aids, and children who use cochlear implants.
PMID- 24350698
TI - Formal carbon insertion of N-tosylhydrazone into B-B and B-Si bonds: gem
diborylation and gem-silylborylation of sp3 carbon.
AB - A convenient method is developed to synthesize 1,1-diboronates from the
corresponding N-tosylhydrazones. This method is also applicable to synthesize 1
silyl-1-boron compounds. Meanwhile, derivatization and consecutive Pd-catalyzed
cross-coupling reactions with 1,1-boronates were explored, demonstrating the
synthetic potential of 1,1-diboronates.
PMID- 24350697
TI - Major findings of the LOCHI study on children at 3 years of age and implications
for audiological management.
AB - OBJECTIVE: This article describes the major findings of the Longitudinal Outcomes
of Children with Hearing Impairment (LOCHI) study. DESIGN: A population-based
prospective cohort study; with randomized controlled trials of hearing aid
prescription and non-linear frequency compression. SAMPLE: 451 children in New
South Wales, Victoria and Southern Queensland. RESULTS: Significant predictors of
language outcomes at 3 years of age included severity of hearing loss, gender,
presence of additional disabilities, maternal education, and age at cochlear
implantation. Although prescription did not have a significant effect on
outcomes, its influence on loudness and hearing aid safety has implications for
management. After controlling for a range of predictor variables, nonlinear
frequency compression did not have a significant effect on outcomes. For the same
hearing sensitivity, the presence of auditory neuropathy did not have a
significant effect on outcomes. CONCLUSIONS: These findings form the basis for
evidence-based guidelines for management of children with hearing loss.
PMID- 24350699
TI - Analyses by UPLC Q-TOF MS of products of aflatoxin B(1) after ozone treatment.
AB - Analysing the products of ozone-treated aflatoxin B1 (AFB1) is essential in order
to study the practical use of ozone treatment. In this paper, the products of
AFB1 were investigated using ultra-performance liquid chromatography-quadrupole
time-of-flight mass spectrometry (UPLC Q-TOF MS). The products were well
separated using UPLC, and the accurate masses of all the products were determined
using Q-TOF MS. Finally, the possible pathways of fragmentation ion generation
from the products of AFB1 and the structures of four products were proposed. From
the view of the proposed structures of products, the C8-C9 double bond in the
terminal furan ring was destroyed. According to the structure-activity
relationship, the toxicity of products was significantly reduced compared with
that of AFB1. The result indicated that ozone was an effective agent for
degrading AFB1, and UPLC Q-TOF MS was a useful analytical tool for proposing and
identifying a series of unknown products.
PMID- 24350700
TI - Bilirubin is an independent factor inversely associated with glycated hemoglobin
level in pediatric patients with type 1 diabetes.
AB - OBJECTIVE: Bilirubin is a potent antioxidant, and serum total bilirubin (STB)
concentrations correlate negatively with cardiovascular risk. In adult diabetic
patients and in healthy adults, a negative correlation between STB and glycated
hemoglobin (HbA1c) has been reported. We investigated whether there is such an
association in children and adolescents with type 1 diabetes mellitus. METHODS:
The study group included 224 patients with type 1 diabetes duration of more than
12 months. Patients with suspected or confirmed hemolytic anemia or liver
dysfunction were excluded. RESULTS: A statistically significant negative
correlation was found between STB and HbA1c (R = -0.15; p = 0.024), which
retained its significance in multivariate analysis (beta = -0.18, p = 0.005).
Patients' age and daily insulin dose were positively correlated with HbA1c
levels, whereas other variables included in the multivariate analysis [sex,
diabetes duration, insulin regimen, C-peptide, hemoglobin, mean corpuscular
hemoglobin concentration (MCHC), alanine transaminase (ALT), and aspartate
transaminase (AST)] did not correlate with HbA1c. The mean HbA1c level in
patients with STB >1.2 mg/dL (>21 umol/L; the threshold for clinical diagnosis of
Gilbert's syndrome) was lower than in patients with STB <=1.2 mg/dL (<=21
umol/L), and the mean difference was 0.63% (6.9 mmol/mol; 95% CI: 0.11-1.16%).
CONCLUSIONS: These results show that in young patients with type 1 diabetes, STB
concentration is an independent factor inversely associated with HbA1c level.
Further studies should investigate the background and long-term effects of this
association.
PMID- 24350701
TI - Biomimetic nitration of conjugated linoleic acid: formation and characterization
of naturally occurring conjugated nitrodienes.
AB - Nitro-conjugated linoleic acids (NO2-cLA), endogenous nitrodiene lipids which act
as inflammatory signaling mediators, were isolated and single isomers purified
from the biomimetic acidic nitration products of conjugated linoleic acid (CLA).
Structures were elucidated by means of detailed NMR and HPLC-MS/MS spectroscopic
analysis and the relative double bond configurations assigned. Additional
synthetic methods produced useful quantities and similar isomeric distributions
of these unusual and reactive compounds for biological studies and isotopic
standards, and the potential conversion of nitro-linoleic to nitro-conjugated
linoleic acids was explored via a facile base-catalyzed isomerization. This
represents one of the few descriptions of naturally occurring conjugated nitro
dienes (in particular, 1-nitro 1,3-diene), an unusual and highly reactive motif
with few biological examples extant.
PMID- 24350702
TI - New stable QTLs for berry weight do not colocalize with QTLs for seed traits in
cultivated grapevine (Vitis vinifera L.).
AB - BACKGROUND: In grapevine, as in other fruit crops, fruit size and seed content
are key components of yield and quality; however, very few Quantitative Trait
Loci (QTLs) for berry weight and seed content (number, weight, and dry matter
percentage) have been discovered so far. To identify new stable QTLs for marker
assisted selection and candidate gene identification, we performed simultaneous
QTL detection in four mapping populations (seeded or seedless) with various
genetic backgrounds. RESULTS: For berry weight, we identified five new QTLs, on
linkage groups (LGs) 1, 8, 11, 17 and 18, in addition to the known major QTL on
LG 18. The QTL with the largest effect explained up to 31% of total variance and
was found in two genetically distant populations on LG 17, where it colocalized
with a published putative domestication locus. For seed traits, besides the major
QTLs on LG 18 previously reported, we found four new QTLs explaining up to 51% of
total variance, on LGs 4, 5, 12 and 14. The previously published QTL for seed
number on LG 2 was found related in fact to sex. We found colocalizations between
seed and berry weight QTLs only for the major QTL on LG 18 in a seedless
background, and on LGs 1 and 13 in a seeded background. Candidate genes belonging
to the cell number regulator CNR or cytochrome P450 families were found under the
berry weight QTLs on LGs 1, 8, and 17. The involvement of these gene families in
fruit weight was first described in tomato using a QTL-cloning approach. Several
other interesting candidate genes related to cell wall modifications, water
import, auxin and ethylene signalling, transcription control, or organ identity
were also found under berry weight QTLs. CONCLUSION: We discovered a total of
nine new QTLs for berry weight or seed traits in grapevine, thereby increasing
more than twofold the number of reliable QTLs for these traits available for
marker assisted selection or candidate gene studies. The lack of colocalization
between berry and seed QTLs suggests that these traits may be partly dissociated.
PMID- 24350704
TI - Breastfeeding infants with phenylketonuria in the United States and Canada.
AB - OBJECTIVE: This study described the prevalence and duration of mothers'
breastfeeding infants with phenylketonuria (PKU) and explored factors related to
duration of breastfeeding as a surrogate for breastfeeding success. SUBJECTS AND
METHODS: Descriptive analysis as performed from an international Internet survey
of mothers (n=103) who met the inclusion criteria: (1) at least 21 years of age,
(2) able to read and write in English, (3) child with PKU, and (4) living in the
United States or Canada. RESULTS: Of the 103 mothers, 89 (86%) initiated
breastfeeding immediately following delivery, whereas 14 (14%) chose bottle
feeding. In comparison to breastfeeding after delivery, significantly fewer
mothers breastfed after diagnosis (McNemar's chi(2)=30.33, p<0.001; n=72 vs.
n=89). Breastfeeding duration ranged from less than 1 month to 24 months with one
modal duration category (n=20, 22%) at less than 1 month. The timing of the
addition of commercial infant formula to supplement breastfeeding or expressed
mothers' milk was associated with a shorter duration of breastfeeding among
infants with PKU: chi(2) (42, n=73)=88.13, p<0.001. CONCLUSIONS: PKU is treated
with phenylalanine (Phe) restriction. Breastfeeding infants with PKU is
challenging in part because Phe intake is difficult to determine precisely. We
studied breastfeeding duration in infants with PKU and factors associated with
success. Further research should identify the unique needs of mothers'
breastfeeding infants with PKU to guide the development of interventions specific
to these mothers to support their efforts to continue breastfeeding after the
diagnosis of PKU.
PMID- 24350711
TI - Photodamage and the importance of photoprotection in biomolecular-powered device
applications.
AB - In recent years, an enhanced understanding of the mechanisms underlying
photobleaching and photoblinking of fluorescent dyes has led to improved
photoprotection strategies, such as reducing and oxidizing systems (ROXS) that
reduce blinking and oxygen scavenging systems to reduce bleaching. Excitation of
fluorescent dyes can also result in damage to catalytic proteins (e.g.,
biomolecular motors), affecting the performance of integrated devices. Here, we
characterized the motility of microtubules driven by kinesin motor proteins using
various photoprotection strategies, including a microfluidic deoxygenation
device. Impaired motility of microtubules was observed at high excitation
intensities in the absence of photoprotection as well as in the presence of an
enzymatic oxygen scavenging system. In contrast, using a polydimethylsiloxane
(PDMS) microfluidic deoxygenation device and ROXS, not only were the fluorophores
slower to bleach but also moving the velocity and fraction of microtubules over
time remained unaffected even at high excitation intensities. Further, we
demonstrate the importance of photoprotection by examining the effect of
photodamage on the behavior of a switchable mutant of kinesin. Overall, these
results demonstrate that improved photoprotection strategies may have a profound
impact on functional fluorescently labeled biomolecules in integrated devices.
PMID- 24350703
TI - Taste of milk from inflamed breasts of breastfeeding mothers with mastitis
evaluated using a taste sensor.
AB - BACKGROUND: The refusal of infants to suckle from a breast that is inflamed with
mastitis suggests that the taste of the milk has changed. However, the taste of
milk from a breast with mastitis has never been empirically determined. The
present study compares the taste of milk from breastfeeding mothers with or
without mastitis and identifies specific changes in the taste of milk from
mothers with mastitis. SUBJECTS AND METHODS: The intensity of four basic tastes
(sourness, saltiness, bitterness, and umami) of breastmilk from 24 healthy
mothers at 3-5 days and at 2-3, 4-5, and 8-10 weeks postpartum and from 14
mothers with mastitis was determined objectively using a taste sensor. The
intensity of each basic taste and the concentrations of main taste substances in
milk were compared between the inflamed breasts and the normal breasts of control
mothers or the contralateral asymptomatic breast of mothers with unilateral
mastitis. RESULTS: The transition from colostrum to mature milk was accompanied
by changes in the taste of the milk, such as decreased saltiness and umami and
increased bitterness and sourness. Umami and saltiness increased in milk from
inflamed breasts. Contents of sodium, glutamate, and guanosine monophosphate
increased in milk from inflamed breasts. CONCLUSIONS: Tastes that were
specifically associated with inflamed breasts appeared to include an increase in
umami and saltiness, which might have resulted from an increased content in
factors associated with umami and sodium.
PMID- 24350712
TI - Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an
amino analogue of thalidomide.
AB - The sedative and antiemetic drug thalidomide [alpha-(N-phthalimido)glutarimide]
was withdrawn in the early 1960s because of its potent teratogenic effects but
was approved for the treatment of lesions associated with leprosy in 1998 and
multiple myeloma in 2006. The mechanism of teratogenicity of thalidomide still
remains unclear, but it is well-established that metabolism of thalidomide is
important for both teratogenicity and cancer treatment outcome. Thalidomide is
oxidized by various cytochrome P450 (P450) enzymes, the major one being P450
2C19, to 5-hydroxy-, 5'-hydroxy-, and dihydroxythalidomide. We previously
reported that P450 3A4 oxidizes thalidomide to the 5-hydroxy and dihydroxy
metabolites, with the second oxidation step involving a reactive intermediate,
possibly an arene oxide, that can be trapped by glutathione (GSH) to GSH adducts.
We now show that the dihydroxythalidomide metabolite can be further oxidized to a
quinone intermediate. Human P450s 2J2, 2C18, and 4A11 were also found to oxidize
5-hydroxythalidomide to dihydroxy products. Unlike P450s 2C19 and 3A4, neither
P450 2J2, 2C18, nor 4A11 oxidized thalidomide itself. A recently approved amino
analogue of thalidomide, pomalidomide (CC-4047, Actimid), was also oxidized by
human liver microsomes and P450s 2C19, 3A4, and 2J2 to the corresponding
phthalimide ring-hydroxylated product.
PMID- 24350713
TI - The fibrotic microenvironment as a heterogeneity facet of hepatocellular
carcinoma.
AB - It has long been recognized that hepatocellular carcinoma heterogeneity arises
from variation in the microenvironment or from genomic alteration. Only recently
it has become clear that non-genetic alterations, such as cytoskeletal
rearrangement, protein localization and formation of protein complexes, are also
involved in generating phenotype variability. These proteome fluctuations cause
genetically identical cells to vary significantly in their responsiveness to
microenvironment stimuli. In the cirrhotic liver pre-malignant hepatocytes are
continuously exposed to abnormal microenvironments, such as direct contact with
activated hepatic stellate cells (HSCs) and extracellular matrix components.
These abnormal environments can have pronounced influences on the epigenetic
aspects of cells, translating into abnormal phenotypes. Here we discuss non
genetic causes of phenotypic heterogeneity of hepatocellular carcinoma, with an
emphasis on variability of membrane protein complexes and transferred functions
raising important implications for diagnosis and treatment.
PMID- 24350716
TI - A new approach for the automatic evaluation of the solidification structure in
steel using orientational entropy filtering.
AB - We present a new method for the automatic evaluation of the dendritic
solidification structure in metallurgical micrographs of solidified steel. The
evaluation of the microstructural parameters such as the primary dendrite arm
spacing and the primary grain size are of high importance due to their direct
relationship with the internal quality and mechanical properties of the cast
product. Given the repeated geometric features in the micrographs and the regular
pattern in colour intensity, we applied a filter mask to determine the local
entropies within the masks in order to detect the centre coordinates of each
individual dendrite. The orientation of the dendrites was determined by rotating
the filter mask over each pixel to find the orientation which corresponds to the
lowest entropy value. The segmentation of the microstructure was then performed
via Delaunay tessellation and subsequent transformation of the triangular mesh
into a rectangular grid, enabling the determination of the desired
microstructural parameters.
PMID- 24350717
TI - Fast forward selection for generalized estimating equations with a large number
of predictor variables.
AB - We propose a new variable selection criterion designed for use with forward
selection algorithms; the score information criterion (SIC). The proposed
criterion is based on score statistics which incorporate correlated response
data. The main advantage of the SIC is that it is much faster to compute than
existing model selection criteria when the number of predictor variables added to
a model is large, this is because SIC can be computed for all candidate models
without actually fitting them. A second advantage is that it incorporates the
correlation between variables into its quasi-likelihood, leading to more
desirable properties than competing selection criteria. Consistency and
prediction properties are shown for the SIC. We conduct simulation studies to
evaluate the selection and prediction performances, and compare these, as well as
computational times, with some well-known variable selection criteria. We apply
the SIC on a real data set collected on arthropods by considering variable
selection on a large number of interactions terms consisting of species traits
and environmental covariates.
PMID- 24350715
TI - Verrucous carcinoma of the head and neck - not a human papillomavirus-related
tumour?
AB - Association between verrucous carcinoma (VC) of the head and neck and human
papillomaviruses (HPV) is highly controversial. Previous prevalence studies
focused mostly on alpha-PV, while little is known about other PV genera. Our aim
was to investigate the prevalence of a broad spectrum of HPV in VC of the head
and neck using sensitive and specific molecular assays. Formalin-fixed, paraffin
embedded samples of 30 VC and 30 location-matched normal tissue samples were
analysed, by using six different polymerase chain reaction-based methods
targeting DNA of at least 87 HPV types from alpha-PV, beta-PV, gamma-PV and MU-PV
genera, and immunohistochemistry against p16 protein. alpha-PV, gamma-PV and MU
PV were not detected. beta-PV DNA was detected in 5/30 VC (16.7%) and in 18/30
normal tissue samples (60.0%): HPV-19, -24 and -36 were identified in VC, and HPV
5, -9, -12, -23, -24, -38, -47, -49 and -96 in normal tissue, whereas HPV type
was not determined in 2/5 cases of VC and in 6/18 normal tissue samples. p16
expression was detected in a subset of samples and was higher in VC than in
normal tissue. However, the reaction was predominantly cytoplasmic and only
occasionally nuclear, and the extent of staining did not exceed 75%. Our results
indicate that alpha-PV, gamma-PV and MU-PV are not associated with
aetiopathogenesis of VC of the head and neck. beta-PV DNA in a subset of VC and
normal tissue might reflect incidental colonization, but its potential biological
significance needs further investigation.
PMID- 24350718
TI - Balancing novelty with confined chemical space in modern drug discovery.
AB - INTRODUCTION: The concept of chemical space has broad applications in drug
discovery. In response to the needs of drug discovery campaigns, different
approaches are followed to efficiently populate, mine and select relevant
chemical spaces that overlap with biologically relevant chemical spaces. AREAS
COVERED: This paper reviews major trends in current drug discovery and their
impact on the mining and population of chemical space. We also survey different
approaches to develop screening libraries with confined chemical spaces balancing
physicochemical properties. In this context, the confinement is guided by
criteria that can be divided in two broad categories: i) library design focused
on a relevant therapeutic target or disease and ii) library design focused on the
chemistry or a desired molecular function. EXPERT OPINION: The design and
development of chemical libraries should be associated with the specific purpose
of the library and the project goals. The high complexity of drug discovery and
the inherent imperfection of individual experimental and computational
technologies prompt the integration of complementary library design and screening
approaches to expedite the identification of new and better drugs. Library design
approaches including diversity-oriented synthesis, biological-oriented synthesis
or combinatorial library design, to name a few, and the design of focused
libraries driven by target/disease, chemical structure or molecular function are
more efficient if they are guided by multi-parameter optimization. In this
context, consideration of pharmaceutically relevant properties is essential for
balancing novelty with chemical space in drug discovery.
PMID- 24350719
TI - Isolation of two different Ni2Zn complexes with an unprecedented cocrystal formed
by one of them and a "coordination positional isomer" of the other.
AB - A new homometallic trinuclear Ni(II) complex [(NiL)2Ni(NCS)2] (1) and three
heterometallic trinuclear Ni(II)-Zn(II)-Ni(II) complexes [(NiL)2Zn(NCS)2] (2),
[(NiL)2Zn(NCS)2(CH3OH)2].2CH3OH (3) and {[(NiL)2Zn(NCS)2(CH3OH)2]}
{[(NiL)2Zn(NCS)2]} (4) have been synthesized by using the "complex as ligand"
approach with the "metalloligand" [NiL] (H2L = N,N'-bis(salicylidene)-1,3
propanediamine) and thiocyanate in different ratios. All the complexes have been
structurally and magnetically characterized. In the isomorphous complexes 1 and
2, the two terminal square planar Ni atoms and the central octahedral nickel atom
(in 1) or zinc atom (in 2) are arranged in a bent structure where two cis kappaN
SCN(-) thiocyanate ions are coordinated to the central atom. The chemical
composition of 3 is very similar to that of 2 but, in 3, the central Zn atom is
tetrahedral and the kappaN-SCN(-) thiocyanate ions occupy an axial position of
each terminal nickel atom (which now are octahedral with the sixth position
occupied by a methanol molecule). Complex 4 consists of two closely related
trinuclear units 4A and 4B. In 4A, the coordination environments of the metals
are identical to those of 3 whereas 4B is a "coordination position isomer" of
complex 2 with the central square pyramidal Zn and one of the terminal square
pyramidal Ni atoms coordinated by two kappaN-SCN(-) thiocyanate ions. Complex 4
is a unique example of a cocrystal formed by two similar trinuclear units (4A and
4B) where 4A is identical to an existing complex (3) and 4B is a "coordination
position isomer" of another existing complex (2).
PMID- 24350721
TI - Cancer inflammation and inflammatory biomarkers: can neutrophil, lymphocyte, and
platelet counts represent the complexity of the immune system?
PMID- 24350714
TI - High protein intake is associated with low prevalence of frailty among old
Japanese women: a multicenter cross-sectional study.
AB - BACKGROUND: Protein intake has been inversely associated with frailty. However,
no study has examined the effect of the difference of protein sources (animal or
plant) or the amino acid composing the protein on frailty. Therefore, we examined
the association of protein and amino acid intakes with frailty among elderly
Japanese women. METHODS: A total of 2108 grandmothers or acquaintances of
dietetic students aged 65 years and older participated in this cross-sectional
multicenter study, which was conducted in 85 dietetic schools in 35 prefectures
of Japan. Intakes of total, animal, and plant protein and eight selected amino
acids were estimated from a validated brief-type self-administered diet history
questionnaire and amino acid composition database. Frailty was defined as the
presence of three or more of the following four components: slowness and weakness
(two points), exhaustion, low physical activity, and unintentional weight loss.
RESULTS: The number of subjects with frailty was 481 (23%). Adjusted ORs (95% CI)
for frailty in the first, second, third, fourth, and fifth quintiles of total
protein intake were 1.00 (reference), 1.02 (0.72, 1.45), 0.64 (0.45, 0.93), 0.62
(0.43, 0.90), and 0.66 (0.46, 0.96), respectively (P for trend = 0.001). Subjects
categorized to the third, fourth, and fifth quintiles of total protein intake
(>69.8 g/d) showed significantly lower ORs than those to the first quintile (all
P <0.03). The intakes of animal and plant protein and all selected amino acids
were also inversely associated with frailty (P for trend <0.04), with the
multivariate adjusted OR in the highest compared to the lowest quintile of 0.73
for animal protein and 0.66 for plant protein, and 0.67-0.74 for amino acids,
albeit that the ORs for these dietary variables were less marked than those for
total protein. CONCLUSIONS: Total protein intake was significantly inversely
associated with frailty in elderly Japanese women. The association of total
protein with frailty may be observed regardless of the source of protein and the
amino acid composing the protein.
PMID- 24350722
TI - The rate of charge tunneling is insensitive to polar terminal groups in self
assembled monolayers in Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn junctions.
AB - This paper describes a physical-organic study of the effect of uncharged, polar,
functional groups on the rate of charge transport by tunneling across self
assembled monolayer (SAM)-based large-area junctions of the form
Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn. Here Ag(TS) is a template-stripped silver
substrate, -M- and -T are "middle" and "terminal" functional groups, and EGaIn is
eutectic gallium-indium alloy. Twelve uncharged polar groups (-T = CN, CO2CH3,
CF3, OCH3, N(CH3)2, CON(CH3)2, SCH3, SO2CH3, Br, P(O)(OEt)2, NHCOCH3,
OSi(OCH3)3), having permanent dipole moments in the range 0.5 < MU < 4.5, were
incorporated into the SAM. A comparison of the electrical characteristics of
these junctions with those of junctions formed from n-alkanethiolates led to the
conclusion that the rates of charge tunneling are insensitive to the replacement
of terminal alkyl groups with the terminal polar groups in this set. The current
densities measured in this work suggest that the tunneling decay parameter and
injection current for SAMs terminated in nonpolar n-alkyl groups, and polar
groups selected from common polar organic groups, are statistically
indistinguishable.
PMID- 24350723
TI - Web-based participatory surveillance of infectious diseases: the Influenzanet
participatory surveillance experience.
AB - To overcome the limitations of the state-of-the-art influenza surveillance
systems in Europe, we established in 2008 a European-wide consortium aimed at
introducing an innovative information and communication technology approach for a
web-based surveillance system across different European countries, called
Influenzanet. The system, based on earlier efforts in The Netherlands and
Portugal, works with the participation of the population in each country to
collect real-time information on the distribution of influenza-like illness cases
through web surveys administered to volunteers reporting their symptoms (or lack
of symptoms) every week during the influenza season. Such a large European-wide
web-based monitoring infrastructure is intended to rapidly identify public health
emergencies, contribute to understanding global trends, inform data-driven
forecast models to assess the impact on the population, optimize the allocation
of resources, and help in devising mitigation and containment measures. In this
article, we describe the scientific and technological issues faced during the
development and deployment of a flexible and readily deployable web tool capable
of coping with the requirements of different countries for data collection,
during either a public health emergency or an ordinary influenza season. Even
though the system is based on previous successful experience, the implementation
in each new country represented a separate scientific challenge. Only after more
than 5 years of development are the existing platforms based on a plug-and-play
tool that can be promptly deployed in any country wishing to be part of the
Influenzanet network, now composed of The Netherlands, Belgium, Portugal, Italy,
the UK, France, Sweden, Spain, Ireland, and Denmark.
PMID- 24350725
TI - SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal
toxicity in Portuguese rheumatoid arthritis patients.
AB - AIM: The aim of our study was to characterize the association of
clinicopathological variables and the SLC19A1/RFC-1 G80A polymorphism in
methotrexate (MTX)-related toxicity in Portuguese patients with rheumatoid
arthritis. PATIENTS & METHODS: The study included 233 consecutively recruited
patients with rheumatoid arthritis under MTX treatment. The SLC19A1 G80A
polymorphism was evaluated by PCR-RFLP. RESULTS: Statistical analysis revealed
that SLC19A1 80G carriers had increased risk of gastrointestinal toxicity (odds
ratio [OR]: 2.61, p = 0.019) and that regular folic acid supplementation was
associated with both overall and gastrointestinal toxicity protection (OR: 0.15,
p < 0.001 and OR: 0.19, p < 0.001, respectively). Multivariate analysis confirmed
the association of SLC19A1 80G and regular folic acid supplementation to
gastrointestinal toxicity (OR: 5.53 and 0.13, respectively). Moreover, a
multivariate Cox regression model demonstrated a higher risk of earlier
gastrointestinal toxicity in SLC19A1 80G carriers (hazard ratio: 3.63, p =
0.002). CONCLUSION: SLC19A1 G80A genotyping may be a useful tool for clinicians
to identify patients at higher risk for developing gastrointestinal toxicity
related to MTX treatment.
PMID- 24350726
TI - Modulation of bone morphogenic protein signaling in T-cells for cancer
immunotherapy.
AB - Immunotherapy is becoming an increasingly attractive therapeutic alternative for
conventional cancer therapy. In recent years Foxp3(+) regulatory T-cells (T(R))
were identified as the major obstacle to effective cancer immunotherapy. The
abundance of these cells in peripheral blood is increased in patients with
multiple types of cancer and their prevalence among tumor-infiltrating
lymphocytes correlated with poor clinical prognosis. In contrast, removal or
inactivation of T(R) cells led to enhanced anti-tumor immune response and better
efficacy of cancer vaccines. This study reports that Bone Morphogenic Protein
Receptor 1alpha (BMPR1alpha, Alk-3) is expressed by activated effector CD4(+) and
T(R) cells and modulates functions of both cell types. Bone Morphogenic Proteins
(BMPs) belong to the transforming growth factor (TGF)-beta family of cytokines
that also include TGFbeta and activins. BMPs play crucial roles in embryonic
development, tissue differentiation and homeostasis, and development of cancer.
It was demonstrated that BMPs and activins synergize with TGFbeta to regulate
thymic T-cell development, maintain T(R) cells, and control peripheral tolerance.
Inactivation of BMPR1alpha in T-cells results in impaired thymic and peripheral
generation of T(R) cells. BMPR1alpha-deficient activated T-cells produced a
higher level of interferon (IFN)-gamma than BMPR1alpha-sufficient T-cells.
Moreover, transplanted B16 melanoma tumors grew smaller in mice lacking
expression of BMPR1alpha in T-cells and tumors had few infiltrating TR cells and
a higher proportion of CD8(+) T-cells than wild-type mice.
PMID- 24350727
TI - Hepatic effects of aminoglutethimide: a model aromatic amine.
AB - Primary aromatic amine drugs are structural alerts in drug development because of
their association with a high incidence of idiosyncratic drug reactions (IDRs).
If biomarkers could be found that predict IDR risk, it would have a major impact
on drug development. Previous attempts to do this through screening of hepatic
gene expression profiles in rodents treated with aromatic amine drugs found
limited changes. Of the drugs studied, aminoglutethimide (AMG) induced the most
changes, and this led to a more comprehensive study of its effects on the liver.
Brown Norway rats treated with AMG for up to 14 days showed only a transient
elevation of glutamate dehydrogenase. Pathway-specific PCR arrays found few AMG
induced gene changes associated with an immune response and, of these changes,
the majority were involved with innate immunity such as Tlr2, Ticam2, CD14, and
C3. AMG treatment also led to significant changes in the apoptosis and
mitochondrial panel of genes. It was recently found that AMG does induce
significant changes in the bone marrow of rats, and agranulocytosis is a common
IDR caused by AMG. In contrast, liver injury is not a common IDR associated with
AMG. Therefore, the liver may be able to effectively deal with AMG reactive
metabolites, and changes observed in this study may be involved in adaptation.
Myeloperoxidase is also known to be able to oxidize aromatic amines to reactive
metabolites, and these observations suggest that metabolism outside of the liver
may be important for the mechanism of aromatic amine-induced IDRs.
PMID- 24350729
TI - Tandem C-2 functionalization-intramolecular azide-alkyne 1,3-dipolar
cycloaddition reaction: a convenient route to highly diversified 9H
benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]diazepines.
AB - An efficient diversity-oriented synthetic approach to annulated 9H
benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]diazepines has been developed
using a Sc(OTf)3-catalyzed two-component tandem C-2 functionalization
intramolecular azide-alkyne 1,3-dipolar cycloaddition reaction. The reaction
shows high substrate tolerance and provides a library of fused heterocycles that
may lead to novel biologically active compounds or drug lead molecules.
PMID- 24350728
TI - Study protocol to examine the effects of spaceflight and a spaceflight analog on
neurocognitive performance: extent, longevity, and neural bases.
AB - BACKGROUND: Long duration spaceflight (i.e., 22 days or longer) has been
associated with changes in sensorimotor systems, resulting in difficulties that
astronauts experience with posture control, locomotion, and manual control. The
microgravity environment is an important causal factor for spaceflight induced
sensorimotor changes. Whether spaceflight also affects other central nervous
system functions such as cognition is yet largely unknown, but of importance in
consideration of the health and performance of crewmembers both in- and post
flight. We are therefore conducting a controlled prospective longitudinal study
to investigate the effects of spaceflight on the extent, longevity and neural
bases of sensorimotor and cognitive performance changes. Here we present the
protocol of our study. METHODS/DESIGN: This study includes three groups
(astronauts, bed rest subjects, ground-based control subjects) for which each the
design is single group with repeated measures. The effects of spaceflight on the
brain will be investigated in astronauts who will be assessed at two time points
pre-, at three time points during-, and at four time points following a
spaceflight mission of six months. To parse out the effect of microgravity from
the overall effects of spaceflight, we investigate the effects of seventy days
head-down tilted bed rest. Bed rest subjects will be assessed at two time points
before-, two time points during-, and three time points post-bed rest. A third
group of ground based controls will be measured at four time points to assess
reliability of our measures over time. For all participants and at all time
points, except in flight, measures of neurocognitive performance, fine motor
control, gait, balance, structural MRI (T1, DTI), task fMRI, and functional
connectivity MRI will be obtained. In flight, astronauts will complete some of
the tasks that they complete pre- and post flight, including tasks measuring
spatial working memory, sensorimotor adaptation, and fine motor performance.
Potential changes over time and associations between cognition, motor-behavior,
and brain structure and function will be analyzed. DISCUSSION: This study
explores how spaceflight induced brain changes impact functional performance.
This understanding could aid in the design of targeted countermeasures to
mitigate the negative effects of long-duration spaceflight.
PMID- 24350730
TI - Antioxidant and antiapoptotic effects of 1,1'-(biphenyl-4,4'-diyl)-bis(3
(dimethylamino)-propan-1-one) on protecting PC12 cells from Abeta-induced injury.
AB - Abnormal extracellular deposition of beta-amyloid (Abeta) is thought to play a
key role in the pathogenesis of Alzheimer's disease (AD). Preventing Abeta
induced neurotoxicity has become a potential therapeutic approach to improve the
onset and progression of AD. Here we report the synthesis of 1,1'-(biphenyl-4,4'
diyl)-bis(3-(dimethylamino)-propan-1-one) (BDBDP) and evaluate whether it
protects PC12 cells from Abeta1-42-induced cytotoxicity in PC12 cells. Treating
cells with Abeta1-42 significantly reduced cell viability and mitochondrial
membrane potential while also significantly increasing apoptosis and production
of reactive oxygen species (ROS). Pretreating the cells with BDBDP significantly
ameloriated these Abeta1-42-induced effects. Futhermore, BDBDP strongly reduced
pro-apoptotic signaling in response to ROS by reducing levels of activated
caspase-3 and increasing the ratio of Bcl-2 to Bax. These findings provide
evidence that BDBDP protects against Abeta1-42-induced neurotoxicity in PC12
cells by inhibiting oxidative stress and cell apoptosis.
PMID- 24350732
TI - Teaming up: feasibility of an online treatment environment for adolescents with
type 1 diabetes.
AB - OBJECTIVE: To evaluate the feasibility of an online interactive treatment
environment for adolescents with type 1 diabetes, called Sugarsquare, to
supplement usual care. RESEARCH DESIGN AND METHODS: Sugarsquare provides easily
accessible contact with the diabetes team, peer support, and treatment overview.
Of 120 eligible patients, 62 adolescents aged 11-21 (M = 15.23, SD = 2.00) were
assigned to a usual-care group (n = 31) or a usual-care + intervention group (n =
31). Feasibility was assessed in terms of acceptability, demand, practicability,
integration, and efficacy in a 9-month study-period. RESULTS: Assessment of
acceptability and demand revealed that 20 adolescents in the intervention group
(65%) logged in at least once; 16 adolescents (52%) logged in repeatedly. Usage
resulted in 5795 page-views, 3580 chat-messages, 427 forum-messages, and in 40
private interactions between 11 adolescents (35%) and professionals. Assessment
of practicability revealed that all 13 professionals (100%) accessed the
intervention. Slow processing speed and security procedures formed obstacles for
usage. Assessment of integration showed that international standards for diabetes
care (International Diabetes Federation/International Society for Pediatric and
Adolescent Diabetes/American Diabetes Association) were met. Assessment of
efficacy revealed improvement in the intervention group in evaluation of care
(Patients' Evaluation of Quality of Diabetes), F(1,30) = 5.35, p < 0.05, and
quality of life, communication (PedsQL), F(1,30) = 11.65, p <0.05. The latter was
correlated with posted chat-messages (r = 0.42, p < 0.05). No between-group
differences were found. CONCLUSIONS: This study shows that Sugarsquare is
feasible in adolescents with type 1 diabetes. It meets a demand in adolescents
and can support professionals when organizing on-going care according to
international standards. Results are promising and next steps are a full-scale
randomized controlled trial and subsequent implementation in daily care.
PMID- 24350731
TI - The issue of mandatory vaccination for healthcare workers in Europe.
AB - Mandatory policies have occasionally been implemented, targeting optimal
vaccination uptake among healthcare workers (HCWs). Herein, we analyze the
existing recommendations in European countries and discuss the feasibility of
implementing mandatory vaccination for HCWs. As reflected by a survey among
vaccine experts from 29 European countries, guidelines on HCW vaccination were
issued in all countries, though with substantial differences in targeted
diseases, HCW groups and type of recommendation. Mandatory policies were only
exceptionally implemented. Results from a second survey suggested that such
policies would not become easily adopted, and recommendations might work better
if focusing on specific HCW groups and appropriate diseases such as hepatitis B,
influenza and measles. In conclusion, guidelines for HCW vaccination, but not
mandatory policies, are widely adopted in Europe. Recommendations targeting
specific HCW groups and diseases might be better accepted and facilitate higher
vaccine uptake than policies vaguely targeting all HCW groups.
PMID- 24350733
TI - Review of radiation therapy services for neurofibromatosis (NF2) patients in
England.
AB - OBJECTIVE: It is widely accepted that stereotactic radiosurgery (SRS) is less
effective in controlling NF2-related vestibular schwannomas (VS-NF2), than
sporadic VS. Concerns persist regarding the risks of malignant transformation and
the development of secondary tumours. In recent years there has been an increase
in the number of centres offering SRS and fractionated stereotactic radiotherapy
(SRT) services for VS. The NF2 National Commissioning Group service framework has
recommended limiting radiation therapies for VS-NF2 to SRS (Gamma Knife) provided
in Sheffield. The aims of this review were to: 1) Establish the current provision
of SRT and SRS services in England. 2) Determine the radiation therapies employed
for NF2 patients since 2000. 3) Determine the feasibility of identifying a
national cohort of NF2 patients in England who have received radiation therapy
since 2000. METHODS: The lead clinicians managing VS patients in the major
regional neurosurgical units in England, and those providing SRS services to NF2
patients were contacted and when possible, databases were examined. RESULTS: A
total of 18 NHS centres and 2 private centres were included. This included the
four NF2 'hub centres' (Cambridge, London, Oxford and Manchester). Their NF2
databases identified 4, 8, 23 and 42 VS-NF2 treatments with SRS or SRT,
respectively since 2000. Eleven centres reported that they had referred VS-NF2
patients exclusively to Sheffield. Each estimated that they had referred no more
than one patient per year. The survey identified four Gamma Knife Centres and six
Linac SRS/SRT centres with the capacity to treat VS and VS-NF2 patients. Of
these, four centres confirmed that they had treated VS-NF2 patients. CONCLUSION:
Since 2000 fewer than 100 SRS and SRT treatments have been undertaken for VS-NF2
patients. Approximately 60% of these have been performed in Sheffield. There is
considerable uncertainty regarding the role of radiation therapy in the
management of VS-NF2 and consequently a range of views and practice.
PMID- 24350734
TI - Diffuse cerebral vasospasm following resection of a hypoglossal schwannoma in a
child.
AB - Diffuse cerebral vasospasm is a rare complication following tumour resection.
This phenomenon seems to be even rarer in the paediatric population and more so
following resections of posterior fossa tumours. Here we report diffuse cerebral
vasospasm in a child with hypoglossal nerve Schwannoma eight days following
resection of the tumour.
PMID- 24350735
TI - Fat necrosis appearing as intraorbital tumour: case report.
AB - A 33-year-old male presented with an extremely rare case of intraorbital fat
necrosis. A magnetic resonance imaging scan showed a 10-mm mass lesion within the
right lateral rectal muscle. Surgical removal was performed. Histological
analysis showed diffuse adipose cells surrounded by macrophage cells. Fat
necrosis was diagnosed.
PMID- 24350736
TI - Microsurgical treatment assisted by intraoperative ultrasound localization: a
controlled trial in patients with hypertensive basal ganglia hemorrhage.
AB - This study investigated the clinical value of performing microsurgical treatment
on hypertensive basal ganglia hemorrhage assisted by intraoperative ultrasound
localization (IUL). A total of 107 patients with hypertensive basal ganglia
hemorrhage were randomly separated into two groups for this controlled clinical
trial. In the IUL group, 51 patients with hypertensive basal ganglia hemorrhage
were operated on with the support of ultrasonic imaging; 56 patients underwent
conventional microsurgery to evacuate the hemorrhage. The results of the two
methods were evaluated according to the rate of hematoma evacuation, re
hemorrhage, mortality, complications, and activities of daily living (ADL). A
greater quantity of the hemorrhage was removed from patients in the IUL group,
with over 90% of masses being eliminated from the brain in 78.43% of these
patients (40 out of 51 patients) compared with 60.71% of patients in the control
group (34 out of 56 patients). The IUL group experienced a lower rate of re
hemorrhage after the operation (7.84%, 4 out of 51 patients) compared with the
control group (17.86%, 10 out of 56 patients). A significant difference in the
ADL score was recorded between the two groups, with ADL scores of the IUL group
exceeding 60 (indicating good recovery) at 6 months after the operative procedure
(P < 0.05). In conclusion, the microsurgical treatment of hypertensive basal
ganglia hemorrhage assisted by IUL improved the precision of the operation. This
procedure removed the hemorrhage and reduced the changes of re-occurrence, as
well as elevated the quality of life of patients after the operation.
PMID- 24350737
TI - Analysis of antimicrobial resistance genes in Aeromonas spp. isolated from
cultured freshwater animals in China.
AB - The development of resistance to antimicrobials used in aquatic animals is an
increasing concern for aquaculture and public health. To monitor the occurrence
of antimicrobial resistance and resistance genes in Aeromonas, a total of 106
isolates were collected from cultured freshwater animals in China from 1995 to
2012. Antimicrobial susceptibilities were determined by the disk diffusion
method. The highest resistance percentage occurred with ampicillin, rifampin,
streptomycin, and nalidixic acid. Most strains were sensitive to
fluoroquinolones, doxycycline, cefotaxime, chloramphenicol, and amikacin. The
isolates from turtle samples had the highest levels of resistance to 11 of the 12
tested antimicrobials when compared with those from fish or shrimp. Polymerase
chain reaction and DNA sequence results showed that all
trimethoprim/sulfamethoxazole-resistant strains contained sul1, and 37.0% were
positive for tetA in tetracycline-resistant strains. ant(3")-Ia was identified in
13 (24.5%) streptomycin-resistant strains. Plasmid-borne quinolone resistance
genes were detected in five Aeromonas hydrophila (4.7%), two of which carried
qnrS2, while the other three strains harbored aac(6')-Ib-cr. Two cefotaxime
resistant A. hydrophila were positive for bla(TEM-1) and bla(CTX-M-3). To our
knowledge, this is the first report characterizing antimicrobial resistance in
Aeromonas isolated from cultured freshwater animals in China, and providing
resistance information of pathogen in Chinese aquaculture.
PMID- 24350746
TI - A recovery-oriented alternative to hospital emergency departments for persons in
emotional distress: "the living room".
AB - Persons with severe mental illness experience episodic crises, resulting in
frequent visits to hospital emergency departments (EDs). EDs, however, are not
the most effective treatment environments for these individuals who might better
be served elsewhere in an environment based on recovery-oriented framework. The
purpose of this study is to describe the lived experience of guests (persons in
emotional distress) and staff (counselors, psychiatric nurses, and peer
counselors) of a community, recovery-oriented, alternative crisis intervention
environment-The Living Room (TLR). The total sample is comprised of 18
participants. An existential phenomenological approach was used for this
qualitative, descriptive, study. Through non-directive in-depth interviews,
participants were asked to describe what stands out to them about The Living
Room. Interviews were audio-recorded, transcribed verbatim, and systematically
analyzed using descriptive phenomenological methods of analysis by an
interdisciplinary and community-based participatory research team. Participants'
experiences in hospital EDs and inpatient psychiatric units contextualized the
phenomenological experience of TLR environment. The final thematic structure of
the experience of TLR included the following predominant themes: A Safe Harbor,
At Home with Uncomfortable Feelings, and It's a Helping, No Judging Zone.
Findings from this qualitative study of a recovery-based alternative to hospital
EDs for persons in emotional distress are supported by anecdotal and empirical
evidence that suggests that non-clinical care settings are perceived as helpful
and positive.
PMID- 24350747
TI - Divergent views of placement decision-making: a qualitative case study.
AB - The purpose of this qualitative case study is to describe the contrasting
perspectives between a family caregiver and the caregiver's professional provider
in regards to the placement decision-making experience of the caregiver. A
qualitative, descriptive, revelatory case study, using a grounded theory approach
for data analysis, was conducted to identify and compare major themes drawn from
interviews with the caregiver-professional dyad. The case is described on the
basis of three interviews, two caregiver interviews (pre- and post-placement) and
one health professional interview. The 77-year-old caregiver in this case was a
wife caring for her 88-year-old husband who was diagnosed with Alzheimer's
disease. The health professional was a social worker who led the support group
the caregiver attended. Separate and private interviews were conducted by the
principal investigator with the caregiver and health professional. Analysis
revealed 11 major emerging categories that were compared from the caregiver's and
professional's perspective. The perspectives of the family caregiver and the
health professional had some elements that were congruent and some that were
incongruent. Professionals may be unaware that they are not providing the kind of
help that the situation requires. In particular, anticipatory guidance is needed
before crisis events make placement immediately necessary. Further research is
needed to identify what kind of conditions contribute to smoother decision-making
processes and long-term care transitions for caregivers of relatives with
dementia.
PMID- 24350748
TI - Emergence of Yalom's therapeutic factors in a peer-led, asynchronous, online
support group for family caregivers.
AB - Support groups fill a critical void in the health care system, harnessing the
power of shared experiences to provide support to group members. Likewise, family
caregivers fill a void in the health care system, providing billions in unpaid
care to the chronically ill. Caregiver support groups offer an opportunity for
alleviating the psychological burden of caregiving. The power of any group,
including a support group, to foster psychological well-being lies in its ability
to cultivate Yalom's therapeutic factors. Gaps in the literature remain regarding
the ability of non-prototypical groups to promote therapeutic mechanisms of
change. The purpose of this study was to determine if and when Yalom's
therapeutic group factors emerged in a peer-led support group delivered in an
asynchronous, online format. Qualitative content analysis utilizing deductive
category application was employed. Participants' responses were coded and
frequency counts were conducted. Results revealed that 9 of 11 therapeutic
factors emerged over the course of the group, with Group Cohesiveness, Catharsis,
Imparting of Information, and Universality occurring most often. Several factors,
including Interpersonal Learning, Corrective Recapitulation of the Primary Family
Group, Imitative Behavior, and Development of Socializing Techniques were absent
or virtually absent, likely due to the peer-led format of the group. Progression
of therapeutic factors over the course of the group is presented. Findings
demonstrate the presence of a variety of Yalom's therapeutic factors in an
asynchronous, peer-led online support group.
PMID- 24350749
TI - Mental health nursing in Australia: resilience as a means of sustaining the
specialty.
AB - As a concept, resilience is continuing to attract considerable attention and its
importance across various life domains is increasingly recognised. Few studies,
however, have defined or considered the notion of the group or collective
resilience of a profession, including the capacity of that profession to
withstand adversity and continue to develop positively in the face of change.
This article considers the notion of resilience from the perspective of the
specialty of mental health nursing, including the ways the specialty has adapted-
and continues to develop--to changes experienced since deinstitutionalisation.
Insights are drawn from a national Delphi study undertaken in Australia to
develop a Scope of Practice for Mental Health Nurses, with responses used as a
springboard to consider the impact of the perceived loss of professional identity
on the collective resilience of the profession. Recommendations for a way forward
for the profession are considered, including the ways in which a collective
professional resilience could be developed to sustain and strengthen the
professional identity of mental health nursing in Australia and across the globe.
PMID- 24350750
TI - Sexual health and dissociative experiences among abused women.
AB - Sexually transmitted infections are a significant public health issue impacting
women. Intimate partner violence (IPV) is one risk factor for STIs/HIV. Women who
are the victims of IPV often experience psychological difficulties, including
dissociation. Dissociative symptoms may play a role in women's ability to
practice safe sex and negotiate condom use, although this has been underexplored.
This mixed methods study examined the dissociative symptoms of 22 women
experiencing IPV and examined the ways in which these women described their own
sexual health and behaviors as well as how they protected themselves from
sexually transmitted infections and HIV.
PMID- 24350751
TI - It's the anxiety: facilitators and inhibitors to nursing students' career
interests in mental health nursing.
AB - Increasing the rate of recruitment of nursing students into mental health nursing
(MHN) is vital to long-term sustainability of health care system support for
people diagnosed with mental illness. However MHN is not a popular career path;
this raises questions about what attitudes and beliefs may divert or attract
students to this specialisation. The current research involved a survey of
undergraduate nursing students at a regional university in Australia to clarify
the nature of relationships between attitudes (e.g., the value of mental health
nursing, stereotypes of people with mental illness) and how they may be
antecedents to considering MHN as a career path. Through a structural equation
model, it was ascertained that anxiety surrounding mental illness leads to less
interest in MHN as a future career and suggests that anxiety is (a) partly due to
negative stereotypes, and (b) countered by preparedness for a MHN role. Beliefs
on how MHN can make a valuable contribution to people's well-being did not affect
interest in pursuing MHN. These findings reconfirm the need to reduce anxiety
about mental illness by educational approaches that effectively prepare students
for MHN, combined with challenging negative stereotypes.
PMID- 24350752
TI - Patients' and family members' experiences of a psychoeducational family
intervention after a first episode psychosis: a qualitative study.
AB - The objective of this study is to explore patients' and family members'
experiences of the different elements of a psychoeducational family intervention.
A qualitative, explorative study was performed based on digitally recorded in
depth interviews with 12 patients and 14 family members. The interview data were
transcribed in a slightly modified verbatim mode and analysed using systematic
text condensation. Six themes that both patients and family members experienced
as important in the family intervention were identified: alliance, support,
anxiety and tension, knowledge and learning, time, and structure. A good
relationship between the group leaders and participants was essential in
preventing dropout. Meeting with other people in the same situation reduced
feelings of shame and increased hope for the future. Hearing real life stories
was experienced as being more important for gaining new knowledge about psychosis
than lectures and workshops. However, many patients experienced anxiety and
tension during the meetings. The group format could be demanding for patients
immediately after a psychotic episode and for those still struggling with
distressing psychotic symptoms. Group leaders need to recognise patients' levels
of anxiety before, and during, the intervention, and consider the different needs
of patients and family members in regards to when the intervention starts, the
group format, and the patients' level of psychotic symptoms. The findings in the
present study may help to tailor family work to better meet the needs of both
patients and family members.
PMID- 24350753
TI - The Nanny State, free will, and public health.
PMID- 24350754
TI - Electroconvulsive therapy: issues for mental health nurses to consider.
PMID- 24350756
TI - Total and inorganic arsenic in foods of the first Hong Kong total diet study.
AB - Arsenic (As) is a metalloid that occurs in different inorganic and organic forms,
which are found in the environment from both natural occurrence and anthropogenic
activity. The inorganic forms of As (iAs) are more toxic as compared with the
organic As, but so far most of the occurrence data in food collected in the
framework of official food control are still reported as total As without
differentiating the various As species. In this paper, total As and iAs contents
of 600 total diet study (TDS) samples, subdivided into 15 different food groups,
were quantified by high-resolution inductively coupled plasma mass spectrometry
(HR-ICP/MS) and hydride generation (HG) ICP/MS respectively. The method detection
limits for both total As and iAs were 3 MUg As kg(-1). As the samples were
prepared for TDS, food items were purchased directly from the market or prepared
as for normal consumption, i.e. table ready, in the manner most representative of
and consistent with cultural habits in Hong Kong as far as practicable. The
highest total As and iAs content were found in 'fish, seafood and their products'
and 'vegetables and their products' respectively. Besides, this paper also
presents the ratios of iAs and total As content in different ready-to-eat food
items. The highest ratio of iAs to total As was found in 'vegetables and their
products'. It is likely that iAs in vegetables maintained its status even after
cooking.
PMID- 24350757
TI - Occurrence of alk(en)ylresorcinols in the fruits of two mango (Mangifera indica
L.) cultivars during on-tree maturation and postharvest storage.
AB - Regarding their relevance for the fungal resistance of mangoes in long supply
chains, the alk(en)ylresorcinols (AR) were quantitated in peel and mesocarp
throughout storage (27 days, 14 degrees C, ethylene absorption). The 12 'Chok
Anan' and 11 'Nam Dokmai #4' lots picked between 83 and 115 days after full bloom
(DAFB) had different harvest maturity indices. The development of dry matter and
fruit growth indicated physiological maturity ~100 DAFB. During storage, all
fruits ripened slowly, mostly until over-ripeness and visible decay. The total AR
contents always ranged at 73 +/- 4.5 and 6.4 +/- 0.7 mg hg(-1) of 'Chok Anan' and
'Nam Dokmai #4' peel dry weight, respectively, but only at 6.7 +/- 0.7 and 0.9 +/
0.1 mg hg(-1) for the corresponding mesocarp (P <= 0.05). These narrow
concentration ranges were contradictory to the decreasing fungal resistance.
Accordingly, the alk(en)ylresorcinols have not been a deciding factor for the
fungal resistance.
PMID- 24350758
TI - Semiparametric analysis of linear transformation models with covariate
measurement errors.
AB - We take a semiparametric approach in fitting a linear transformation model to a
right censored data when predictive variables are subject to measurement errors.
We construct consistent estimating equations when repeated measurements of a
surrogate of the unobserved true predictor are available. The proposed approach
applies under minimal assumptions on the distributions of the true covariate or
the measurement errors. We derive the asymptotic properties of the estimator and
illustrate the characteristics of the estimator in finite sample performance via
simulation studies. We apply the method to analyze an AIDS clinical trial data
set that motivated the work.
PMID- 24350759
TI - Evaluating predictability.
PMID- 24350760
TI - Cu(I)-NHC catalyzed asymmetric silyl transfer to unsaturated lactams and amides.
AB - The first asymmetric silylation of unsaturated lactams and amides using Cu(I)-NHC
catalysts and PhMe2SiBpin has been accomplished. The method has been exploited in
an expedient asymmetric synthesis of the (R)-enantiomer of the nootropic drug
oxiracetam.
PMID- 24350761
TI - Computational insights on the geometrical arrangements of Cu(II) with a mixed
donor N3S3 macrobicyclic ligand.
AB - The macrobicyclic mixed-donor N3S3 cage ligand AMME-N3S3sar (1-methyl-8-amino
3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]eicosane) can form complexes with
Cu(II) in which it acts as hexadentate (N3S3) or tetradentate (N2S2) donor. These
two complexes are in equilibrium that is strongly influenced by the presence of
halide ions (Br(-) and Cl(-)) and the nature of the solvent (DMSO, MeCN, and
H2O). In the absence of halides the hexadentate coordination mode of the ligand
is preferred and the encapsulated complex ("Cu-in(2+)") is formed. Addition of
halide ions in organic solvents (DMSO or MeCN) leads to the tetradentate complex
("Cu-out(+)") in a polyphasic kinetic process, but no Cu-out(+) complex is formed
when the reaction is performed in water. Here we applied density functional
theory calculations to study the mechanism of this interconversion as well as to
understand the changes in the reactivity associated with the presence of water.
Calculations were performed at the B3LYP/(SDD,6-31G**) level, in combination with
continuum (MeCN) or discrete-continuum (H2O) solvent models. Our results show
that formation of Cu-out(+) in organic media is exergonic and involves sequential
halide-catalyzed inversion of the configuration of a N-donor of the macrocycle,
rapid halide coordination, and inversion of the configuration of a S-donor. In
aqueous solution the solvent is found to have an effect on both the
thermodynamics and the kinetics of the reaction. Thermodynamically, the process
becomes endergonic mainly due to the preferential solvation of halide ions by
water, while the kinetics is influenced by formation of a network of H-bonded
water molecules that surrounds the complex.
PMID- 24350763
TI - Single centre prospective study of the efficacy of percutaneous cement
augmentation in the treatment of vertebral compression fractures.
AB - INTRODUCTION: Despite controversial outcomes of recent published trials,
percutaneous cement augmentation remains widely used in managing painful
vertebral compression fractures. We prospectively assessed patients with such
fractures using an eleven-point visual analogue scale for pain and the Qualeffo
41 questionnaire for quality of life. METHODS: Consecutive patients undergoing
percutaneous cement augmentation for painful vertebral compression fractures were
recruited. Patients were assessed pre-procedure by completing a visual analogue
scale for pain, on a scale of 0 to 10. A Qualeffo 41 questionnaire was also
completed. Patients were followed up at 1 week and 3 months. RESULTS: Fifty six
patients were prospectively recruited (111 vertebroplasty and 5 kyphoplasty).
Visual analogue scores dropped from 6.4 +/- 2.3 pre-procedure to 4.0 +/- 2.7 at 1
week (p < 0.0001) and 4.3 +/- 2.7 (p < 0.0001) at 3 months. Three subgroups were
identified; osteoporotic patients (n = 28), a second non-osteoporotic group (n =
20) who had acute fracture following fall and a third group with compression
fractures secondary to metastatic disease (n = 8). At 3-month follow-up, patients
with osteoporotic fractures had reduction in pain score from 6.3 +/- 2.1 to 4.8
+/- 2.7 (p = 0.02). Patients who had traumatic fractures experienced more
significant pain relief, 6.4 +/- 2.6 to 3.8 +/- 2.7 (p = 0.0009) but patients
with malignant fracture had most benefit, 6.0 +/- 3.0 to 1.8 +/- 0.8 (p = 0.01).
Total Qualeffo scores improved from 63 +/- 15 to 49 +/- 22 (p < 0.0001). Within
the domains of the Qualeffo questionnaire, most improvement was seen in pain and
physical function. Median in-patient stay post procedure was one day. CONCLUSION:
In our experience percutaneous cement augmentation is safe and efficacious in the
management of painful VCF related to osteoporosis, trauma and cancer, achieving
rapid and significant pain reduction and improvement in physical function as
measured with a visual analogue scale and the Qualeffo 41 questionnaire.
PMID- 24350764
TI - Spinal dural arteriovenous fistulas--presentation, management and outcome in a
single neurosurgical institution.
AB - OBJECTIVE: To compare the outcome, with respect to treatment modality, of
patients treated with spinal dural arteriovenous fistulas (SDAVF). METHOD:
Retrospective cohort study of patients with SDAVF assessed at a single tertiary
referral centre, between 1999 and 2009. Intervention type, pre-/ post
intervention Aminoff-Logue disability score (ALDS) and recurrence rate were
obtained from medical records. RESULTS: 26 patients were identified with 23
receiving intervention. All patients initially received super selective
angiogram, with 13 undergoing endovascular embolization at this stage, after
discussion between the surgeon and interventional radiologist. Six patients who
underwent embolization had a recurrence. The remaining 10 patients had fistulas
marked during angiography, and were then treated surgically, after discussion.
One of these recurred. The difference in recurrence rate between the two
intervention types was not statistically significant. Fistulas treated with the
embolization material onyx were twice as likely to recur as those treated with
the alternative material, histoacryl-lipiodol. There was a statistically
significant difference between the modes of intervention in relation to clinical
outcome. Surgeries lead to an improvement in neurology, whereas treatment via
embolization did not. Neurological improvement was seen in non-recurring cases,
however deterioration in neurological function occurred with fistula recurrence.
CONCLUSION: Super selective angiography is effective in defining the relevant
vascular anatomy and allows for precise fistula localization during any potential
subsequent surgery. Onyx was associated with a higher recurrence rate, suggesting
it is less suitable as an embolization material for SDAVF treatment. Surgery
appeared to correlate to reversal of neurological impairment seen at
presentation, possibly due to a lower recurrence rate. The study is limited by
small patient numbers, emphasizing the need for further studies of SDAVF
patients.
PMID- 24350766
TI - Respiratory syncytial virus in critically ill adult patients with community
acquired respiratory failure: a prospective observational study.
AB - The incidence of respiratory syncytial virus (RSV) and influenza virus infection
was determined during three RSV seasons in 158 adult patients consecutively
admitted to the intensive care unit with community-acquired respiratory failure.
Nasopharyngeal swabs were tested for the presence of RSV and influenza virus by
real-time polymerase chain reaction. Six patients (4%) were positive for RSV and
all recovered. This finding was in sharp contrast to influenza (23 (15%)
patients, 4 (17%) deaths). In conclusion, even in the midst of the RSV season,
RSV is an infrequent cause of respiratory failure in adults admitted to the
intensive care unit.
PMID- 24350767
TI - Transfer from pediatric to adult health care: effects on diabetes outcomes.
AB - The transfer from pediatric to adult diabetes health care for emerging adults
with type 1 diabetes (T1D) has received increasing attention in the literature.
This review analyzes the effect of this health care transfer on the outcomes of
diabetes care visit attendance, glycemic control, and acute diabetes-related
complications, and assesses the methodological strength of the studies reporting
observational and interventional data. Observational studies, often limited by
incomplete data, report a decline in diabetes care visits but an improvement or
no change in hemoglobin A1c (HbA1c) after transfer to adult care. Results from
studies reporting a transition intervention are restricted by lack of appropriate
control groups and the collection of data both before and after transfer of care.
Very few methodologically strong studies are available to guide clinicians with
the transition from pediatric to adult care, and these shortcomings should be
addressed in future studies designed to facilitate and improve the care of
emerging adults with T1D.
PMID- 24350768
TI - A case of pericardial tuberculoma presenting as a left anterior chest wall mass.
AB - INTRODUCTION: Tuberculosis (TB) can present both in its pulmonary or extra
pulmonary forms. Cardiac tuberculoma previously described only after autopsy is
continuously seen with the advent of more advanced imaging modalities. CASE
REPORT: A 23-year-old male with a four month history of a progressively
increasing left anterior thoracic wall mass of 5 cm in diameter was referred from
oncology for clinical re-evaluation and for echocardiography. Systemic
examination was essentially normal. Transthoracic and trans-oesophageal
echocardiography showed the presence of a pericardial mass around the right
atrioventricular junction. Thoracic CT scan showed an anterior mass in left chest
wall extending to the pericardium and also the presence of mediastinal
lymphadenopathy. Mantoux test was positive and histological examination of tissue
biopsy confirmed the presence of TB. However, blood tests and culture of
aspirated purulent fluid were unyielding. A diagnosis of pericardial tuberculoma
with mediastinal and parietal extension was made and patient was successfully
treated with standard anti-TB chemotherapy. DISCUSSION: The possible differential
diagnoses for chest wall tumors are varied and a high degree of suspicion is
needed to diagnose cardiac tuberculoma especially in endemic regions. Imaging
though helpful in morphological description cannot make precise diagnosis. The
diagnosis depends on histological and culture studies. There is usually a good
evolution with anti-TB treatment. CONCLUSION: In an era of an increasing number
of acquired immune-compromised patients, and with increasing number of diagnoses
of tuberculosis, a diagnosis of cardiac tuberculoma should be considered in
patients presenting with a thoracic wall mass.
PMID- 24350769
TI - Phenylpropanoid pathway is potentiated by silicon in the roots of banana plants
during the infection process of Fusarium oxysporum f. sp. cubense.
AB - Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense, is a disease that
causes large reductions in banana yield worldwide. Considering the importance of
silicon (Si) to potentiate the resistance of several plant species to pathogen
infection, this study aimed to investigate, at the histochemical level, whether
this element could enhance the production of phenolics on the roots of banana
plants in response to F. oxysporum f. sp. cubense infection. Plants of cultivar
Maca, which is susceptible to F. oxysporum f. sp. cubense, were grown in plastic
pots amended with 0 (-Si) or 0.39 g of Si (+Si) per kilogram of soil and
inoculated with race 1 of F. oxysporum f. sp. cubense. The root Si concentration
was increased by 35.6% for +Si plants in comparison to the -Si plants, which
contributed to a 27% reduction in the symptoms of Fusarium wilt on roots. There
was an absence of fluorescence for the root sections of the -Si plants treated
with the Neu and Wilson's reagents. By contrast, for the root sections obtained
from the +Si plants treated with Neu's reagent, strong yellow-orange fluorescence
was observed in the phloem, and lemon-yellow fluorescence was observed in the
sclerenchyma and metaxylem vessels, indicating the presence of flavonoids. For
the root sections of the +Si plants treated with Wilson's reagent, orange
yellowish autofluorescence was more pronounced around the phloem vessels, and
yellow fluorescence was more pronounced around the metaxylem vessels, also
indicating the presence of flavonoids. Lignin was more densely deposited in the
cortex of the roots of the +Si plants than for the -Si plants. Dopamine was
barely detected in the roots of the -Si plants after using the lactic and
glyoxylic acid stain, but was strongly suspected to occur on the phloem and
metaxylem vessels of the roots of the +Si plants as confirmed by the intense
orange-yellow fluorescence. The present study provides new evidence of the
pivotal role of the phenylpropanoid pathway in the resistance of banana plants to
F. oxysporum f. sp. cubense infection when supplied with Si.
PMID- 24350771
TI - Quantitative compositional profiling of conjugated quantum dots with single
atomic layer depth resolution via time-of-flight medium-energy ion scattering
spectroscopy.
AB - We report the quantitative compositional profiling of 3-5 nm CdSe/ZnS quantum
dots (QDs) conjugated with a perfluorooctanethiol (PFOT) layer using the newly
developed time-of-flight (TOF) medium-energy ion scattering (MEIS) spectroscopy
with single atomic layer resolution. The collection efficiency of TOF-MEIS is 3
orders of magnitude higher than that of conventional MEIS, enabling the analysis
of nanostructured materials with minimized ion beam damage and without ion
neutralization problems. The spectra were analyzed using PowerMEIS ion scattering
simulation software to allow a wide acceptance angle. Thus, the composition and
core-shell structure of the CdSe cores and ZnS shells were determined with a 3%
composition uncertainty and a 0.2-nm depth resolution. The number of conjugated
PFOT molecules per QD was also quantified. The size and composition of the QDs
were consistent with those obtained from high-resolution transmission electron
microscopy and X-ray photoelectron spectroscopy, respectively. We suggest TOF
MEIS as a nanoanalysis technique to successfully elucidate the core-shell and
conjugated layer structures of QDs, which is critical for the practical
application of QDs in various nano- and biotechnologies.
PMID- 24350770
TI - MOPED enables discoveries through consistently processed proteomics data.
AB - The Model Organism Protein Expression Database (MOPED,
http://moped.proteinspire.org) is an expanding proteomics resource to enable
biological and biomedical discoveries. MOPED aggregates simple, standardized and
consistently processed summaries of protein expression and metadata from
proteomics (mass spectrometry) experiments from human and model organisms (mouse,
worm, and yeast). The latest version of MOPED adds new estimates of protein
abundance and concentration as well as relative (differential) expression data.
MOPED provides a new updated query interface that allows users to explore
information by organism, tissue, localization, condition, experiment, or keyword.
MOPED supports the Human Proteome Project's efforts to generate chromosome- and
diseases-specific proteomes by providing links from proteins to chromosome and
disease information as well as many complementary resources. MOPED supports a new
omics metadata checklist to harmonize data integration, analysis, and use.
MOPED's development is driven by the user community, which spans 90 countries and
guides future development that will transform MOPED into a multiomics resource.
MOPED encourages users to submit data in a simple format. They can use the
metadata checklist to generate a data publication for this submission. As a
result, MOPED will provide even greater insights into complex biological
processes and systems and enable deeper and more comprehensive biological and
biomedical discoveries.
PMID- 24350772
TI - Activation of cellular immunity and marked inhibition of liver cancer in a mouse
model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1.
AB - BACKGROUND: Cancer is both a systemic and a genetic disease. The pathogenesis of
cancer might be related to dampened immunity. Host immunity recognizes nascent
malignant cells - a process referred to as immune surveillance. Augmenting immune
surveillance and suppressing immune escape are crucial in tumor immunotherapy.
METHODS: A recombinant plasmid capable of co-expressing granulocyte-macrophage
colony- stimulating factor (GM-SCF), interleukin-21 (IL-21), and retinoic acid
early transcription factor-1 (Rae-1) was constructed, and its effects determined
in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for
IL-2 and INF-gamma by ELISA. Liver cancer specimens were isolated for Rae-1
expression by RT-PCR and Western blot, and splenocytes were analyzed by flow
cytometry. RESULTS: The recombinant plasmid inhibited the growth of liver cancer
and prolonged survival of tumor-loaded mice. Activation of host immunity might
have contributed to this effect by promoting increased numbers and cytotoxicity
of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following
expression of GM-SCF, IL-21, and Rae-1. By contrast, the frequency of regulatory
T cells was decreased, Consequently, activated CTL and NK cells enhanced their
secretion of INF-gamma, which promoted cytotoxicity of NK cells and CTL.
Moreover, active CTL showed dramatic secretion of IL-2, which stimulates CTL. The
recombinant expression plasmid also augmented Rae-1 expression by liver cancer
cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer.
CONCLUSIONS: The recombinant expression plasmid inhibited liver cancer by a
mechanism that involved activation of cell-mediated immunity and Rae-1 in liver
cancer.
PMID- 24350774
TI - Lymphatic system: a prospective area for advanced targeting of particulate drug
carriers.
AB - INTRODUCTION: The lymphatic system has a critical role in the immune system's
recognition and response to disease and it is an additional circulatory system
throughout the entire body. Extensive multidisciplinary investigations have been
carried out in the area of lymphatic delivery, and lymphatic targeting has
attracted a lot of attention for providing preferential chemotherapy and
improving bioavailability of drugs that undergo hepatic first-pass metabolism.
AREAS COVERED: This review focuses on progress in the field of lymphatic
therapeutics and diagnosis. Moreover, the anatomy and physiology of the lymphatic
system, particulate drug carriers and different physicochemical parameters of
both modified and unmodified particulate drug carriers and their effect on
lymphatic targeting are addressed. EXPERT OPINION: Particulate drug carriers have
encouraged lymphatic targeting, but there are still challenges in targeting drugs
and bioactives to specific sites, maintaining desired action and crossing all the
physiological barriers. Lymphatic therapy using drug-encapsulated lipid carriers,
especially liposomes and solid lipid nanoparticles, emerges as a new technology
to provide better penetration into the lymphatics where residual disease exists.
Size is the most important criteria when designing nanocarriers for targeting
lymphatic vessels as the transportation of these particles into lymphatic vessels
is size dependent. By increasing our understanding of lymphatic transport and
uptake, and the role of lymphatics in various diseases, we can design new
therapeutics for effective disease control.
PMID- 24350775
TI - Clinical course and seizure outcome of idiopathic childhood epilepsy:
determinants of early and long-term prognosis.
AB - BACKGROUND: Idiopathic epilepsies and epileptic syndromes predominate childhood
and adolescence epilepsy. The aim of the present study was to investigate the
clinical course and outcome of idiopathic childhood epilepsy and identify
variables determining both early and long-term prognosis. METHODS: We followed
303 children with newly diagnosed idiopathic epilepsy aged 1-14 years old, both
prospectively and retrospectively. Outcome was defined at one, 2 and 4 years of
follow-up, as well as at the end of the study period for all patients. Based on
the data collected, patients were classified in four patterns of clinical course:
"excellent", "improving", "relapsing" and "poor". Variables defined at intake and
after the initial year of treatment were analyzed for their prognostic relevance
towards the clinical course and outcome of the patients. RESULTS: The mean age at
seizure onset was 6.7 years and the mean duration of follow-up was 8.3 years
(range 2,0-22,0,SD 4,24). During the initial year of treatment, 70,3% of patients
were seizure-free. The course of epilepsy was "excellent" in 53,1% of the
subjects, "improving" in 22,8%, "relapsing" in 22,1% whereas only 6 children with
idiopathic epilepsy (2%) had a "poor" clinical course exhibiting drug-resistance.
After multivariate analysis, variables predictive of a poor initial response to
therapy were early seizure onset, multiple seizure types and history of status
epilepticus. At the end of follow-up, early response to treatment was of
significant positive predictive value, while the presence of multiple seizure
types and the history of migraine had a negative impact on prognosis.
CONCLUSIONS: In the vast majority of children, the long-term prognosis of
idiopathic epilepsy is favorable. More than half of the patients attain seizure
freedom immediately and their clinical course is considered "excellent". About
one fifth exhibit either an improving or a fluctuating course. Early seizure
onset, multiple seizure types and status epilepticus are predictive of an initial
poor response to treatment in children with idiopathic epilepsy. Initial non
response to treatment, multiple seizure types and history of migraine are
determinants of a less favorable final outcome after long-term follow-up.
PMID- 24350776
TI - Pyrosequencing as a tool for rapid fish species identification and commercial
fraud detection.
AB - The increased consumption of fish products, as well as the occurrence of exotic
fish species in the Mediterranean Sea and in the fish market, has increased the
risk of commercial fraud. Furthermore, the great amount of processed seafood
products has greatly limited the application of classic identification systems.
DNA-based identification allows a clear and unambiguous detection of
polymorphisms between species, permitting differentiation and identification of
both commercial fraud and introduction of species with potential toxic effects on
humans. In this study, a novel DNA-based approach for differentiation of fish
species based on pyrosequencing technology has been developed. Raw and processed
fish products were tested, and up to 25 species of fish belonging to Clupeiformes
and Pleuronectiformes groups were uniquely and rapidly identified. The proper
identification based on short and unique genetic sequence signatures demonstrates
that this approach is promising and cost-effective for large-scale surveys.
PMID- 24350777
TI - Biogenic nanopalladium based remediation of chlorinated hydrocarbons in marine
environments.
AB - Biogenic catalysts have been studied over the last 10 years in freshwater and
soil environments, but neither their formation nor their application has been
explored in marine ecosystems. The objective of this study was to develop a
biogenic nanopalladium-based remediation method for reducing chlorinated
hydrocarbons from marine environments by employing indigenous marine bacteria.
Thirty facultative aerobic marine strains were isolated from two contaminated
sites, the Lagoon of Mar Chica, Morocco, and Priolo Gargallo Syracuse, Italy.
Eight strains showed concurrent palladium precipitation and biohydrogen
production. X-ray diffraction and thin section transmission electron microscopy
analysis indicated the presence of metallic Pd nanoparticles of various sizes (5
20 nm) formed either in the cytoplasm, in the periplasmic space, or
extracellularly. These biogenic catalysts were used to dechlorinate
trichloroethylene in simulated marine environments. Complete dehalogenation of 20
mg L(-1) trichloroethylene was achieved within 1 h using 50 mg L(-1) biogenic
nanopalladium. These biogenic nanoparticles are promising developments for future
marine bioremediation applications.
PMID- 24350778
TI - Faldaprevir (BI 201335) for the treatment of hepatitis C in patients co-infected
with HIV.
AB - Chronic HCV infection affects 130-170 million individuals worldwide and there are
currently 34 million people living with HIV/AIDS. The aim of treatment of HCV is
the elimination of the virus (sustained virological response). With development
of drugs that specifically target HCV replication, direct-acting agents,
sustained virological response rates have dramatically changed for genotype 1
infections. Challenges in the use of direct-acting agents in patients with
HIV/HCV co-infection include the potential for drug-drug interactions between HIV
and HCV drugs, additional drug toxicities and the need for therapy with IFN
alpha. Faldaprevir (FDV), previously known as BI 201335, is a second-wave HCV
NS3/4A protease inhibitor with highly potent in vitro activity against HCV GT
1a/1b and improved pharmacokinetics suitable for once-daily dosing. FDV is
currently in Phase III development. This article will review the pharmacology and
pharmacodynamics of FDV, the efficacy and safety of the drug and explore possible
future developments in the management of chronic hepatitis C infection, focusing
on HIV/HCV co-infected patients.
PMID- 24350779
TI - Endogenous and xenobiotic metabolite profiling of liver extracts from SCID and
chimeric humanized mice following repeated oral administration of troglitazone.
AB - 1. Metabonomic analysis, via a combination of untargeted and targeted liquid
chromatography-mass spectrometry (LC-MS) and untargeted (1)H NMR spectroscopy
based metabolite profiling, was performed on aqueous (AQ) and organic liver
extracts from control (SCID) and chimeric humanized (PXB) mice dosed with
troglitazone at 0, 300 and 600 mg/kg/day for seven days. 2. LC-MS analysis of AQ
liver extracts showed a more "human-like" profile for troglitazone metabolites
for PXB, compared with SCID, mice. 3. LC-MS detected differences in endogenous
metabolites, particularly lipid species in dosed mice, including elevated
triacylglycerols and 1-alkyl,2-acylglycerophosphates as well as lowered
diacylglycerophosphocholines and 1-alkyl,2-acylglycerophosphocholines for PXB
compared with SCID mouse liver extracts. Following drug administration changes in
the relative proportions of the ions for various unsaturated fatty acids were
observed for both types of mouse, some of which were specific to PXB or SCID
mice. 4. (1)H NMR spectroscopy revealed that AQ PXB mouse liver extracts had
elevated amounts of inosine, fumarate, creatine, aspartate, trimethylamine N
oxide, glycerophosphocholine, phosphocholine, choline, glutamine, glutamate,
acetate, alanine and lactate relative to SCID mice and decreased histidine,
glycogen, alpha- and beta-glucose, taurine, and glutathione. Increased uracil and
tyrosine concentrations were detected for PXB mice on troglitazone
administration. 5. Metabonomic profiling thus showed clear differences between
humanized and SCID mice, including after administration of troglitazone.
PMID- 24350780
TI - The lymphatic system plays a major role in the intravenous and subcutaneous
pharmacokinetics of trastuzumab in rats.
AB - Therapeutic monoclonal antibodies are currently delivered mainly via the
intravenous route, since large volumes are often required to deliver a
therapeutic dose. Administration via the subcutaneous route would have several
therapeutic advantages; the absorption mechanisms for antibodies dosed
subcutaneously are poorly understood. This study was conducted to develop a
better understanding of the mechanisms governing the subcutaneous absorption and
trafficking of monoclonal antibodies. Specifically, the role of the lymphatic
system in the absorption and prolonged plasma exposure of trastuzumab was
explored in thoracic lymph duct-cannulated rats after SC and IV dosing. A
population pharmacokinetic model was developed in S-ADAPT to simultaneously fit
all plasma and lymph concentrations and to predict the pharmacokinetics in
nonlymph duct-cannulated animals. The estimated absolute bioavailability of
trastuzumab after SC administration in rats was 85.5%. Following SC
administration, 53.1% of the trastuzumab dose was absorbed via a first-order
process (mean absorption time: 99.6 h) into the peripheral lymph compartment and
32.4% of the dose was absorbed by a Michaelis-Menten process into the central
compartment. Recovery in thoracic lymph over 30 h was 26.7% after SC and 44.1%
after IV administration. This study highlights for the first time the significant
role of the lymphatic system in maintaining the long plasma exposure of
trastuzumab, with the model predicting an extensive distribution of this
monoclonal antibody into the lymph following SC and IV administration. This
extensive direct absorption from the SC injection site into lymph may enable
novel therapeutic strategies for the treatment of lymph resident metastatic
cancer.
PMID- 24350781
TI - Cutaneous collagenous vasculopathy associated with intravascular occlusive fibrin
thrombi.
AB - Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that
clinically resembles generalized essential telangiectasia with only 12 cases
reported to date. The perivascular fibrosis is thought to be due to production of
abnormal collagen by veil cells in the outer vessel walls as a result of unknown
factors. This report is of an 84-year-old male with progressive telangiectasia.
Biopsies showed characteristic features of CCV. In addition, there were multiple
intravascular fibrin thrombi, some organizing and associated with endothelial
cell hyperplasia with recanalization reminiscent of glomeruloid bodies and
simulating reactive angioendotheliomatosis (RAE). Histochemically and
ultrastructurally fibrin was noted within the vessel walls integrating into the
fibrous tissue around the vessels; however, the patient had no evidence of
coagulation disorder, cryoglobulinemia or cold agglutinemia. Immunofluorescence
showed fibrinogen within the vessel walls but no immunoglobulins or C3. As well,
there were minimal inflammatory cells. This suggests pauci-inflammatory injury to
the endothelial cells by unknown angiogenic factors causing local intravascular
fibrin thrombi with fibrin leaking and incorporating into the vessel walls,
eventually leading to reparative perivascular fibrosis. This case suggests that
some cases of CCV are related to a primary local intravascular occlusive
thrombotic microangiopathy. However, the primary triggering factor causing the
endothelial cell damage has yet to be elucidated.
PMID- 24350783
TI - Characterization of a tryptophan 2-monooxygenase gene from Puccinia graminis f.
sp. tritici involved in auxin biosynthesis and rust pathogenicity.
AB - The plant hormone indole-3-acetic acid (IAA) is best known as a regulator of
plant growth and development but its production can also affect plant-microbe
interactions. Microorganisms, including numerous plant-associated bacteria and
several fungi, are also capable of producing IAA. The stem rust fungus Puccinia
graminis f. sp. tritici induced wheat plants to accumulate auxin in infected leaf
tissue. A gene (Pgt-IaaM) encoding a putative tryptophan 2-monooxygenase, which
makes the auxin precursor indole-3-acetamide (IAM), was identified in the P.
graminis f. sp. tritici genome and found to be expressed in haustoria cells in
infected plant tissue. Transient silencing of the gene in infected wheat plants
indicated that it was required for full pathogenicity. Expression of Pgt-IaaM in
Arabidopsis caused a typical auxin expression phenotype and promoted
susceptibility to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000.
PMID- 24350784
TI - Source localization with MEG data: A beamforming approach based on covariance
thresholding.
AB - Reconstructing neural activities using non-invasive sensor arrays outside the
brain is an ill-posed inverse problem since the observed sensor measurements
could result from an infinite number of possible neuronal sources. The sensor
covariance-based beamformer mapping represents a popular and simple solution to
the above problem. In this article, we propose a family of beamformers by using
covariance thresholding. A general theory is developed on how their spatial and
temporal dimensions determine their performance. Conditions are provided for the
convergence rate of the associated beamformer estimation. The implications of the
theory are illustrated by simulations and a real data analysis.
PMID- 24350785
TI - Spirochetemia due to Treponema pallidum using polymerase-chain-reaction assays in
patients with early syphilis: prevalence, associated factors and treatment
response.
AB - Between 2009 and 2013, polymerase-chain-reaction assay was used to detect
Treponema pallidum in the blood samples collected from 296 patients with early
syphilis (241 being HIV infected) and 102 patients (34.5%) had spirochetemia. The
presence of spirochetemia was associated with lower CD4 counts (per 10-cell/mm(3)
decrease, adjusted odds ratio (AOR), 1.020; 95% CI, 1.006-1.036) and secondary
syphilis (AOR, 4.967; 95% CI, 2.016-12.238). Patients with early latent syphilis
were less likely to achieve serological response compared with those with primary
or secondary syphilis (AOR, 0.317; 95% CI, 0.142-0.708). However, serological
response was not affected by presence of spirochetemia or antibiotic regimens.
PMID- 24350786
TI - Regression of brain metastases from breast cancer with eribulin: a case report.
AB - BACKGROUND: Eribulin is a recently approved new therapeutic option for patients
with metastatic breast cancer. According to several reports, eribulin has limited
ability to cross the blood brain barrier. Recently, capecitabine and eribulin
have been recognized as drugs with similar application for patients with advanced
breast cancer. Although there have been several case reports describing the
efficacy of capecitabine against brain metastases, no report of eribulin
demonstrating efficacy for brain metastases exists today. CASE PRESENTATION: We
describe a case of a 57-year-old Japanese woman who was diagnosed with breast
cancer stage IV metastasized to multiple organs including liver and lung. After
she received 3 regimens, she showed evidence of brain metastases, and whole brain
radiation therapy was performed. Lapatinib and capecitabine was then administered
as fourth-line chemotherapy, but the patient was hospitalized due to the
exacerbation of interstitial pneumonitis and progression of brain and liver
metastases. To control the systemic disease, eribulin was commenced as fifth-line
chemotherapy. One month later, a significant response of brain metastases had
been achieved, and this response has persisted for the last 4 months. We now
describe a remarkable antitumor effect of eribulin against brain metastases from
breast cancer. This case is the first report which indicates potential treatment
of brain metastases using this medication. CONCLUSION: This report suggests that
eribulin treatment may be beneficial for breast cancer patients with brain
metastases progressing after whole brain radiation therapy. However, further
clinical studies are warranted to determine the clinical effect of eribulin in
brain metastases.
PMID- 24350787
TI - Learning curve assessment of robot-assisted radical prostatectomy compared with
open-surgery controls from the premier perspective database.
AB - INTRODUCTION: The primary aims of this study were to assess the learning curve
effect of robot-assisted radical prostatectomy (RARP) in a large administrative
database consisting of multiple U.S. hospitals and surgeons, and to compare the
results of RARP with open radical prostatectomy (ORP) from the same settings.
MATERIALS AND METHODS: The patient population of study was from the Premier
Perspective Database (Premier, Inc., Charlotte, NC) and consisted of 71,312
radical prostatectomies performed at more than 300 U.S. hospitals by up to 3739
surgeons by open or robotic techniques from 2004 to 2010. The key endpoints were
surgery time, inpatient length of stay, and overall complications. We compared
open versus robotic, results by year of procedures, results by case volume of
specific surgeons, and results of open surgery in hospitals with and without a
robotic system. RESULTS: The mean surgery time was longer for RARP (4.4 hours,
standard deviation [SD] 1.7) compared with ORP (3.4 hours, SD 1.5) in the same
hospitals (p<0.0001). Inpatient stay was shorter for RARP (2.2 days, SD 1.9)
compared with ORP (3.2 days, SD 2.7) in the same hospitals (p<0.0001). The
overall complications were less for RARP (10.6%) compared with ORP (15.8%) in the
same hospitals, as were transfusion rates. ORP results in hospitals without a
robot were not better than ORP with a robot, and pretreatment co-morbidity
profiles were similar in all cohorts. Trending of results by year of procedure
showed no differences in the three cohorts, but trending of RARP results by
surgeon experience showed improvements in surgery time, hospital stay, conversion
rates, and complication rates. CONCLUSIONS: During the initial 7 years of RARP
development, outcomes showed decreased hospital stay, complications, and
transfusion rates. Learning curve trends for RARP were evident for these
endpoints when grouped by surgeon experience, but not by year of surgery.
PMID- 24350789
TI - Failure of ESI spectra to represent metal-complex solution composition: a study
of lanthanide-carboxylate complexes.
AB - Electrospray ionization-mass spectrometry (ESI-MS) shows great promise as a rapid
method to identify metal-ligand complexes in solution. However, its application
for quantitative determination of the distribution of species present in
complicated equilibria is still in its infancy, and a direct correlation between
ions observed in the gas phase and species expected in solution must be made with
caution. The present work focuses on a seemingly simple system; the complexation
of lanthanide cations with the acetate ligand. Using a high resolution quadrupole
time-of-flight mass spectrometer, ions created by electrospray of solutions
containing trivalent neodymium and acetate were identified. The gas phase
distribution of species was compared to the solution phase speciation predicted
using thermodynamic complexation constants. Apparent gas phase speciation
diagrams were constructed as a function of solution conditions and fragmentation
potential. Despite the expected variability of metal-ligand complexes as solution
conditions change, the observed gas phase speciation was independent of the metal
to ligand ratio but dependent on the operating conditions of the ESI-MS.
PMID- 24350788
TI - Metal-free synthesis of ynones from acyl chlorides and potassium
alkynyltrifluoroborate salts.
AB - A straightforward method for the preparation of ynones from acyl chlorides and
potassium alkynyltrifluoroborate salts has been developed. The one-pot reaction
proceeds rapidly in the presence of a Lewis acid without exclusion of air and
moisture.
PMID- 24350790
TI - Chlamydia trachomatis infection during pregnancy: knowledge, test practices, and
attitudes of Dutch midwives.
AB - BACKGROUND: Chlamydia trachomatis infection in pregnancy may lead to adverse
pregnancy outcomes. In the Netherlands, testing for C. trachomatis is based on
risk assessment. We assessed midwives' knowledge, test practices, assessment of
risk behavior, and attitudes regarding testing for C. trachomatis infection
during pregnancy. We evaluated the association between midwives' characteristics
and their knowledge of C. trachomatis infection in terms of symptomatology and
outcomes. METHODS: This was a cross-sectional study among primary care midwives
in the Netherlands. Between September and November 2011, midwives from all Dutch
primary care midwifery practices were invited to complete a questionnaire about
C. trachomatis infection. RESULTS: Of the 518 midwives invited to participate in
this study, 331 (63.9%) responded. The overall median knowledge score for
questions about symptomatology and outcomes was 10 out of a maximum score of 15.
The median knowledge score was higher among midwives in urban areas. In total,
239 (72.2%) midwives reported testing pregnant women for C. trachomatis. The
primary reason for testing was a request by the woman herself (96.2%), followed
by symptoms of infection (89.1%), risk behavior (59.3%), and risk factors for
infection (7.3%). Almost 25% of midwives showed positive attitudes towards
universal screening for C. trachomatis. CONCLUSIONS: Midwives were knowledgeable
about symptoms of infection, but less about outcomes. Midwives test pregnant
women for C. trachomatis mainly on the women's request. Otherwise, testing is
based on symptoms of infection rather than on known risk factors. This may
contribute to under-diagnosis and under-treatment, leading to maternal,
perinatal, and neonatal morbidity.
PMID- 24350793
TI - Comparison of utility weighted DMFT with patient-reported oral well-being.
AB - This study investigated a method of measuring oral health, as opposed to
measuring disease. The objective was to compare DMF score and whole mouth utility
scores to a patient-reported outcome measure (PROM). Disutility values for lost
and restored teeth were used to weight the decayed, missing and filled
teeths(DMFTs) of 10 adult patients. This gave two whole mouth utility scores
(WMU). These scores were then compared with a patient-reported oral health
outcome measure recorded by the use of a visual analogue scale (VAS). The anchors
for the VAS were 'my mouth could not be worse' and 'my mouth could not be
better'. There was a positive correlation (r = 0.6457) between WMU1 and the
patient-reported outcome measure (P < 0.05) and a negative correlation (r =
0.8383) between WMU1 and DMFT which was significant at the P < 0.01 level. There
was a statistically significant positive correlation of r = 0.7926 between WMU2
and the patient-reported outcome measure (P < 0.01) and a negative correlation (r
= -0.9393) between WMU2 and DMFT (P < 0.01). The Pearson's correlation between
DMFT and the patient-reported outcome measure was -0.8757, which was significant
at the 0.01 level. Patient reports of their perceived level of health correlate
well with DMFT scores. Weighting DMFT scores according to the differential values
assigned to missing, or missing and filled, teeth does not increase the degree of
correlation between the measure and the patients' personal quantification of
their oral health. Decayed, missing and filled teeth therefore seems to
adequately capture the patient's sense of well-being.
PMID- 24350791
TI - Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine
phosphatase-1B on the insulin receptor phosphorylation.
AB - BACKGROUND: Growth factor receptor-bound protein 14 (Grb14) is an adapter protein
implicated in receptor tyrosine kinase signaling. Grb14 knockout studies
highlight both the positive and negative roles of Grb14 in receptor tyrosine
kinase signaling, in a tissue specific manner. Retinal cells are post-mitotic
tissue, and insulin receptor (IR) activation is essential for retinal neuron
survival. Retinal cells express protein tyrosine phosphatase-1B (PTP1B), which
dephosphorylates IR and Grb14, a pseudosubstrate inhibitor of IR. This project
asks the following major question: in retinal neurons, how does the IR overcome
inactivation by PTP1B and Grb14? RESULTS: Our previous studies suggest that
ablation of Grb14 results in decreased IR activation, due to increased PTP1B
activity. Our research propounds that phosphorylation in the BPS region of Grb14
inhibits PTP1B activity, thereby promoting IR activation. We propose a model in
which phosphorylation of the BPS region of Grb14 is the key element in promoting
IR activation, and failure to undergo phosphorylation on Grb14 leads to both
PTP1B and Grb14 exerting their negative roles in IR. Consistent with this
hypothesis, we found decreased phosphorylation of Grb14 in diabetic type 1
Ins2Akita mouse retinas. Decreased retinal IR activation has previously been
reported in this mouse line. CONCLUSIONS: Our results suggest that
phosphorylation status of the BPS region of Grb14 determines the positive or
negative role it will play in IR signaling.
PMID- 24350794
TI - High birth weights but not excessive weight gain prior to manifestation are
related to earlier onset of diabetes in childhood: 'accelerator hypothesis'
revisited.
AB - AIMS/HYPOTHESIS: Aim of this study was to test Wilkin's 'accelerator hypothesis':
whether excessive weight gain accelerates the onset of type 1 diabetes. SUBJECTS
AND METHODS: Anthropometric birth data of 1117 children who developed diabetes
between 1988 and April 2013 were compared with those of a sex, age, and
gestational age matched, contemporary regional control group (n = 54 344). Cases
were divided into three manifestation groups (G1:0-4.9 yr, G2:5-9.9 yr, and G3:
10-20 yr). Furthermore, growth data of 540 children with diabetes were compared
with controls (n = 134 249) in pre-, peri-, and post-onset intervals (interval: 1
6). Also, correlation of age at onset and body mass index (BMI) standard
deviation score (SDS) at this point of time were examined. RESULTS: Cases had
significantly higher SDSs for birth weight when compared with controls (boys: p =
0.007, girls: p = 0.002). Children with early manifestation had the highest mean
of birth weight SDS (G1>G2>G3), (p = 0.22, adjusted r(2) = 0.001). BMI SDS trend
curves of cases are slightly higher compared with those of the healthy controls.
This was only significant in years after diagnosis (interval 6, p < 0.000). Cases
did not show excessive weight gain in any of the examined intervals before the
onset of diagnosis (interval 1-3). One year after diagnosis, we found an inverse
correlation between age at diagnosis and BMI SDS at diabetes manifestation. The
youngest children at diagnosis (G1) had the lowest BMI SDS at manifestation and
vice versa (G197 pg/mL, IL-8 >40 pg/mL and C-reactive protein >90 mg/L were identified as
being connected with adverse clinical outcome through univariate logistic
analysis. Significant survival differences were also observed between patients
with serum C-reactive protein <90 mg/L or creatinine <90 MUmol/L and those with
higher levels. Our data demonstrated that high viral load, and the resulting
intense inflammatory responses, played an important role in H7N9 pathogenesis.
Though immunomodulatory treatment has potential benefits, the focus of clinical
management should be on preventing the intense cytokine response by early
diagnosis and effective antiviral treatment.
PMID- 24350811
TI - From the editor-in-chief's desk.
PMID- 24350812
TI - Methylphenidate side effect profile is influenced by genetic variation in the
attention-deficit/hyperactivity disorder-associated CES1 gene.
AB - OBJECTIVE: A naturalistic, prospective study of the influence of genetic
variation on dose prescribed, clinical response, and side effects related to
stimulant medication in 77 children with attention-deficit/hyperactivity disorder
(ADHD) was undertaken. The influence of genetic variation of the CES1 gene coding
for carboxylesterase 1A1 (CES1A1), the major enzyme responsible for the first
pass, stereoselective metabolism of methylphenidate, was investigated. METHODS:
Parent- and teacher-rated behavioral questionnaires were collected at baseline
when the children were medication naive, and again at 6 weeks while they were on
medication. Medication dose, prescribed at the discretion of the treating
clinician, and side effects, were recorded at week 6. Blood and saliva samples
were collected for genotyping. Single nucleotide polymorphisms (SNPs) were
selected in the coding, non-coding and the 3' flanking region of the CES1 gene.
Genetic association between CES1 variants and ADHD was investigated in an
expanded sample of 265 Irish ADHD families. Analyses were conducted using
analysis of covariance (ANCOVA) and logistic regression models. RESULTS: None of
the CES1 gene variants were associated with the dose of methylphenidate provided
or the clinical response recorded at the 6 week time point. An association
between two CES1 SNP markers and the occurrence of sadness as a side effect of
short-acting methylphenidate was found. The two associated CES1 markers were in
linkage disequilibrium and were significantly associated with ADHD in a larger
sample of ADHD trios. The associated CES1 markers were also in linkage
disequilibrium with two SNP markers of the noradrenaline transporter gene
(SLC6A2). CONCLUSIONS: This study found an association between two CES1 SNP
markers and the occurrence of sadness as a side effect of short-acting
methylphenidate. These markers were in linkage disequilibrium together and with
two SNP markers of the noradrenaline transporter gene.
PMID- 24350810
TI - Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal
neurons by Gprin1 regulates growth.
AB - Cholinergic signaling plays an important role in regulating the growth and
regeneration of axons in the nervous system. The alpha7 nicotinic receptor
(alpha7) can drive synaptic development and plasticity in the hippocampus. Here,
we show that activation of alpha7 significantly reduces axon growth in
hippocampal neurons by coupling to G protein-regulated inducer of neurite
outgrowth 1 (Gprin1), which targets it to the growth cone. Knockdown of Gprin1
expression using RNAi is found sufficient to abolish the localization and calcium
signaling of alpha7 at the growth cone. In addition, an alpha7/Gprin1 interaction
appears intimately linked to a Galphao, growth-associated protein 43, and CDC42
cytoskeletal regulatory pathway within the developing axon. These findings
demonstrate that alpha7 regulates axon growth in hippocampal neurons, thereby
likely contributing to synaptic formation in the developing brain.
PMID- 24350813
TI - An open-label extension study of the safety and efficacy of risperidone in
children and adolescents with autistic disorder.
AB - OBJECTIVE: The purpose of this study was to evaluate the long-term safety and
efficacy of risperidone in treating irritability and related behaviors in
children and adolescents with autistic disorders. METHODS: In this 6 month (26
week) open-label extension (OLE) study, patients (5-17 years of age, who
completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly
dosed with risperidone based on body weight. The maximum allowed dose was 1.25
mg/day for those weighing 20 to <45 kg, and 1.75 mg/day for those weighing >= 45
kg. The study primarily assessed risperidone's safety; efficacy was assessed as a
secondary end-point. RESULTS: Fifty-six (71%) out of 79 enrolled patients
completed the OLE; the most common discontinuations were for insufficient
response (7 [9%]) or adverse events (AE) (5 [6%]). The most common (>= 5%
frequency in the total group) AEs were increased appetite (11% [n=9]); increased
weight and vomiting (9% [n=7] each); sedation, pyrexia, and upper respiratory
tract infection (8% [n=6] each); nasopharyngitis (6% [n=5]); and somnolence and
fatigue (5% [n=4] each). Extrapyramidal AEs were reported in 6 (8%) patients.
Increase in mean weight (11-15%) and body mass index (5-10%) occurred; one
patient discontinued because of weight increase. One potentially prolactin
related AE (irregular menstruation) was reported. The risperidone high-dose group
had the greatest mean improvement in sleep visual analog scale (24.6). All groups
showed additional improvement in efficacy scale scores during the OLE.
CONCLUSIONS: During this OLE, safety findings with risperidone treatment (maximum
weight-based dose of 1.25 mg/day or 1.75 mg/day) were consistent with those
observed in the DB phase, and with the current safety information for risperidone
in autistic, psychiatric, and behavioral disorders. Patients experienced some
additional improvement in irritability and related behaviors. CLINICAL TRIALS
REGISTRY: This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).
PMID- 24350814
TI - Comparison among clomipramine, fluoxetine, and placebo for the treatment of
anxiety disorders in children and adolescents.
AB - OBJECTIVE: The purpose of this study was to test the efficacy of clomipramine and
fluoxetine, controlled by placebo, and compare their action in children and
adolescents with anxiety disorders. METHOD: Thirty subjects (ages 7-17 years),
who were diagnosed with generalized anxiety disorder and/or separation anxiety
disorder and/or social phobia, were submitted to a 12 week double-blind,
randomized, placebo-controlled trial of clomipramine and fluoxetine. The
instruments included: the Schedule for Affective Disorders and Schizophrenia, the
Multidimensional Anxiety Scale for Children, the Children's Depression Inventory,
the Clinical Global Impressions, and the Children's Global Assessment Scale.
RESULTS: All groups (clomipramine [n=9], fluoxetine [n=10], placebo [n=11])
showed a significant improvement after 12 weeks of treatment. There were
significant differences between the fluoxetine and placebo groups in some ratings
of anxiety severity and impairment. No significant differences were observed
between clomipramine and placebo groups or between fluoxetine and clomipramine
groups. CONCLUSIONS: Treatment with placebo showed an unusual high response rate.
Clomipramine showed similar efficacy compared with fluoxetine, although it was
not superior to placebo.
PMID- 24350815
TI - Ceftriaxone and infection in first episode adolescent psychosis.
PMID- 24350816
TI - God-mother-baby: what children think they know.
AB - This study tested one hundred and nine 3- to 6-year-old children on a knowledge
ignorance task about knowledge in humans (mother, baby) and God. In their
responses, participants not reliably grasping that seeing leads to knowing in
humans (pre-representational) were significantly influenced by own knowledge and
marginally by question format. Moreover, knowledge was attributed significantly
more often to mother than baby and explained by agent-based characteristics. Of
participants mastering the task for humans (representational), God was largely
conceived as ignorant "man in the sky" by younger and increasingly as
"supernatural agent in the sky" by older children. Evidence for egocentrism and
for anthropomorphizing God lends support to an anthropomorphism hypothesis. First
time evidence for an agent-based conception of others' knowledge in pre
representational children is presented.
PMID- 24350817
TI - Molecular deciphering of the ABO system as a basis for novel diagnostics and
therapeutics in ABO incompatible transplantation.
AB - In recent years ABO incompatible kidney transplantation (KTx) has become a more
or less clinical routine procedure with graft and patient survival similar to
those of ABO compatible transplants. Antigen-specific immunoadsorption (IA) for
anti-A and anti-B antibody removal constitutes in many centers an important part
of the treatment protocol. ABO antibody titration by hemagglutination is guiding
the treatment; both if the recipient can be transplanted as well as in cases of
suspected rejections if antibody removal should be performed. Despite the overall
success of ABO incompatible KTx, there is still room for improvements and an
extension of the technology to include other solid organs. Based on an increased
understanding of the structural complexity and tissue distribution of ABH
antigens and the fine epitope specificity of the ABO antibody repertoire,
improved IA matrices and ABO antibody diagnostics should be developed.
Furthermore, understanding the molecular mechanisms behind accommodation of ABO
incompatible renal allografts could make it possible to induce long-term
allograft acceptance also in human leukocyte antigen (HLA) sensitized recipients
and, perhaps, also make clinical xenotransplantation possible.
PMID- 24350818
TI - Myristicyclins A and B: antimalarial procyanidins from Horsfieldia spicata from
Papua New Guinea.
AB - An antimalarial screen for plants collected from Papua New Guinea identified an
extract of Horsfieldia spicata as having activity. Isolation of the active
constituents led to the identification of two new compounds: myristicyclins A (1)
and B (2). Both compounds are procyanidin-like congeners of myristinins lacking a
pendant aromatic ring. Myristicyclin A was found to inhibit the ring,
trophozoite, and schizont stages of Plasmodium falciparum at similar
concentrations in the mid-MUM range.
PMID- 24350821
TI - How to feed 10 billion?
PMID- 24350820
TI - Corticotropic axis drive of overnight cortisol secretion is suppressed in
adolescents and young adults with type 1 diabetes mellitus.
AB - CONTEXT: Type 1 diabetes mellitus (T1DM) is a pro-inflammatory stress state,
which, with its attendant hyperglycemia, likely disrupts hypothalamo-pituitary
adrenal (HPA) control, further dysregulating glucose homeostasis. OBJECTIVE: To
test the hypothesis that endogenous adrenocorticotropic hormone (ACTH)-cortisol
dose-responsive drive, estimated analytically, is significantly accentuated in
adolescents and young adults with T1DM compared with healthy individuals. DESIGN,
SETTING, PATIENTS, AND INTERVENTIONS: This was a pilot study of 11 volunteers
with T1DM and 10 controls, ages 16-30 yr, at a medical center. Subjects underwent
overnight frequent blood sampling (every 10 min for ACTH and cortisol and every
60 min for blood glucose) from 10 pm to 8 am. T1DM volunteers maintained their
home insulin regimen. MAIN OUTCOMES: Deconvolution analysis and dose-response
estimates were the key outcomes. RESULTS: Mean free cortisol, but not ACTH,
concentrations were lower in the T1DM group compared with controls (p = 0.012).
Non-invasive ACTH-cortisol dose-response estimates revealed that T1DM patients
had reduced ACTH efficacy (maximal cortisol secretion, p = 0.009), reduced ACTH
potency as quantified by greater EC50 (ACTH concentration driving half-maximal
cortisol secretion, p = 0.04), and increased ACTH sensitivity (more positive ACTH
cortisol slope, p = 0.03). Post-hoc gender comparisons indicated that these
differences were limited to females. Linear regression in women showed a strong
correlation of both ACTH efficacy and EC50 with C-peptide levels (both p < 0.01).
CONCLUSION: Compared with healthy individuals, T1DM patients manifest decreased
overnight adrenal responsiveness to endogenous ACTH leading to lower free
cortisol concentrations. These findings suggest impaired stress-related
adaptations of the HPA axis in T1DM.
PMID- 24350822
TI - Adherence among Italian paediatricians to the Italian guidelines for the
management of fever in children: a cross sectional survey.
AB - BACKGROUND: Italian guidelines for the management of fever in children (IFG) have
been published in 2009 and thereafter disseminated in all country. A survey was
conducted before their publication and three years later to investigate their
impact on knowledge and behaviors of paediatricians. METHODS: A questionnaire was
administered to convenient samples of paediatricians in 2009 and in 2012,
eliciting information about fever definition, methods of temperature measurement,
and antipyretic use. Differences in responses between 2009 and 2012 and between
paediatricians who were or were not aware of the IFG were evaluated. RESULTS: The
responses rates were 74% (480/648) in 2009 and 69% (300/434) in 2012. In 2012
168/300 (56%) of participants were aware of the IFG. The proportion of
paediatricians who correctly would never suggest the use of physical methods
increased from 18.7% to 36.4% (P < 0.001). In 2009 11% of paediatricians declared
that the use of antipyretic drugs depends on patient discomfort and did not use a
temperature cut off. In 2012 this percentage reached 45.3% (P < 0.001). Alternate
use of antipyretics decreased from 27.0% to 11.3% (P < 0.001). Use of rectal
administration of antipyretics in absence of vomiting decreased from 43.8% in
2009 to 25.3% in 2012 (P < 0.001). In general, improvements were more striking in
paediatricians who were aware of the IFG than in those who were not aware of
them. CONCLUSIONS: Behaviours of Italian paediatricians improved over time.
However, some wrong attitudes need to be further discouraged, including use of
physical methods and misuse of rectal administration. Further strategy to
disseminate the IFG could be needed.
PMID- 24350823
TI - Plasmodium falciparum is dependent on de novo myo-inositol biosynthesis for
assembly of GPI glycolipids and infectivity.
AB - Intra-erythrocytic stages of the malaria parasite, Plasmodium falciparum, are
thought to be dependent on de novo synthesis of phosphatidylinositol, as red
blood cells (RBC) lack the capacity to synthesize this phospholipid. The myo
inositol headgroup of PI can either be synthesized de novo or scavenged from the
RBC. An untargeted metabolite profiling of P. falciparum infected RBC showed that
trophozoite and schizont stages accumulate high levels of myo-inositol-3
phosphate, indicating increased de novo biosynthesis of myo-inositol from glucose
6-phosphate. Metabolic labelling studies with (13) C-U-glucose in the presence
and absence of exogenous inositol confirmed that de novo myo-inositol synthesis
occurs in parallel with myo-inositol salvage pathways. Unexpectedly, while both
endogenous and scavenged myo-inositol was used to synthesize bulk PI, only de
novo-synthesized myo-inositol was incorporated into GPI glycolipids. Moreover,
gene disruption studies suggested that the INO1 gene, encoding myo-inositol 3
phosphate synthase, is essential in asexual parasite stages. Together these
findings suggest that P. falciparum asexual stages are critically dependent on de
novo myo-inositol biosynthesis for assembly of a sub-pool of PI species and GPI
biosynthesis. These findings highlight unexpected complexity in phospholipid
biosynthesis in P. falciparum and a lack of redundancy in some nutrient salvage
versus endogenous biosynthesis pathways.
PMID- 24350824
TI - Investigation of gender-specific exhaled breath volatome in humans by GCxGC-TOF
MS.
AB - Exploring gender-specific metabolic differences in biofluids provides a basic
understanding of the physiological and metabolic phenotype of healthy subjects.
Many reports have shown gender-specific metabolome profiles in the urine and
serum of healthy subjects; however, limited studies focusing on exhaled human
breath are available in the literature. In this study, we profiled the exhaled
breath (~450 mL) volatile organic compounds (VOCs) of 47 healthy volunteers (age:
19-47; 23 male (M) and 24 female (F)) using a multidimensional gas chromatography
and mass spectrometry and employed chemometric analysis to identify gender
specific VOCs. Eleven exhaled breath VOCs were identified from both uni and
multivariate analysis from a training set (M = 15, F = 15) that could
differentiate the genders within a healthy population. A partial least-squares
discriminate analysis (PLS-DA) model built using these putative markers showed
high accuracy in predicting (area under the receiver operating characteristic
curve >0.9) a hold out/test sample set (n = 17). The outcomes of this report open
up new avenues to undertake larger studies to elucidate the association of
exhaled breath metabolites with gender-specific disease phenotypes and
pharmacokinetics in the future.
PMID- 24350825
TI - Bayesian geostatistical modelling of soil-transmitted helminth survey data in the
People's Republic of China.
AB - BACKGROUND: Soil-transmitted helminth infections affect tens of millions of
individuals in the People's Republic of China (P.R. China). There is a need for
high-resolution estimates of at-risk areas and number of people infected to
enhance spatial targeting of control interventions. However, such information is
not yet available for P.R. China. METHODS: A geo-referenced database compiling
surveys pertaining to soil-transmitted helminthiasis, carried out from 2000
onwards in P.R. China, was established. Bayesian geostatistical models relating
the observed survey data with potential climatic, environmental and socioeconomic
predictors were developed and used to predict at-risk areas at high spatial
resolution. Predictors were extracted from remote sensing and other readily
accessible open-source databases. Advanced Bayesian variable selection methods
were employed to develop a parsimonious model. RESULTS: Our results indicate that
the prevalence of soil-transmitted helminth infections in P.R. China considerably
decreased from 2005 onwards. Yet, some 144 million people were estimated to be
infected in 2010. High prevalence (>20%) of the roundworm Ascaris lumbricoides
infection was predicted for large areas of Guizhou province, the southern part of
Hubei and Sichuan provinces, while the northern part and the south-eastern
coastal-line areas of P.R. China had low prevalence (<5%). High infection
prevalence (>20%) with hookworm was found in Hainan, the eastern part of Sichuan
and the southern part of Yunnan provinces. High infection prevalence (>20%) with
the whipworm Trichuris trichiura was found in a few small areas of south P.R.
China. Very low prevalence (<0.1%) of hookworm and whipworm infections were
predicted for the northern parts of P.R. China. CONCLUSIONS: We present the first
model-based estimates for soil-transmitted helminth infections throughout P.R.
China at high spatial resolution. Our prediction maps provide useful information
for the spatial targeting of soil-transmitted helminthiasis control interventions
and for long-term monitoring and surveillance in the frame of enhanced efforts to
control and eliminate the public health burden of these parasitic worm
infections.
PMID- 24350826
TI - The stereoselectivity of CYP2C19 on R- and S-isomers of proton pump inhibitors.
AB - PPIs are mainly metabolized by CYP2C19. It has a stereoselectivity effect on R-
and S-isomers of PPIs according to previous studies. However, no study has been
reported to elucidate the binding mechanism at the atomic level based on the
CYP2C19 crystal structure. Recently, the advent of the first crystal structure of
CYP2C19 allowed us to take in silico approaches including MD simulation, MM/GBSA
calculation, energy decomposition, and alanine scanning to explore the
stereoselectivity of CYP2C19 on R- and S-isomers of PPIs. The key residues
responsible for the selective binding for R- and S-isomers of omeprazole,
lansoprazole, and pantoprazole are disclosed by free energy and alanine scanning
analysis. Structural analysis showed that chiral isomers of PPIs alter their
conformations to have strong binding affinities with CYP2C19. Furthermore, a
theoretical pharmacophore model of PPIs was obtained with the importance of
pharmacophore feature being weighted, basing on our results. Our results are
valuable for designing and synthesizing new generation of PPIs in the future.
PMID- 24350827
TI - Seroprevalence and exposure to risk factors for leptospirosis among veterinary
students at Massey University.
AB - AIMS: To determine the seroprevalence and quantify putative risk factors for
exposure to leptospirosis both within and outside the veterinary curriculum among
undergraduate veterinary students at Massey University, New Zealand. METHODS: A
cross-sectional study was conducted from September 2010 to November 2011. In
total, 302 students were blood sampled, with serum tested by microscopic
agglutination test (MAT) for antibodies to Leptospira borgpetersenii serovars
Hardjobovis, Leptospira interrogans Pomona and Leptospira borgpetersenii Ballum.
Information on demographic characteristics, potential exposure within and outside
the veterinary curriculum in the previous 18 months, and previous leptospirosis
like clinical history were recorded using an online questionnaire. RESULTS: All
students were MAT negative for each serovar, using a cut-point of >=1:48.
Potential exposure to animal urine within and outside the veterinary curriculum
was reported by 259/302 (85.8%) and 150/302 (49.7%) of the students,
respectively. The median number of potential exposures to animal urine by each
student within the veterinary curriculum in the previous 18 months was 63 (min 1,
max 155). The other potential exposures among respondents included home slaughter
(63/302; 20.9%), hunting (43/302; 14.2%) and outdoor activities involving
exposure to fresh water (241/302; 79.8%). CONCLUSIONS: This study demonstrated
that these veterinary students were at low risk of contracting leptospirosis,
despite frequent exposure to potential sources of infection. The findings in this
study contribute to a broader understanding of the occupational risk of
leptospirosis. Data describe the level of animal exposure in veterinary students,
which can support other zoonotic disease studies in this group.
PMID- 24350828
TI - Microscopic investigation of single-wall carbon nanotube uptake by Daphnia magna.
AB - The objectives of this study were to determine the extent of absorption of
functionalized single-wall carbon nanotubes (SWCNTs) across the gut epithelial
cells in Daphnia magna. Several microscopic techniques were utilized, including
micro-Raman spectroscopy, high-resolution transmission electron microscopy
(HRTEM) and selective area diffraction (SAD). In an effort to examine the
variation in uptake due to surface properties, four groups of differently
functionalized SWCNTs were used: hydroxylated (OH-SWCNTs), silicon dioxide (SiO2
SWCNTs), poly aminobenzenesulfonic acid (PABS-SWCNTs) and polyethylene glycol
(PEG-SWCNTs). Raman spectroscopy was able to detect OH-SWCNTs within the gut, but
lacked the spatial resolution that is needed to identify lower concentrations of
SWCNTs that may have been absorbed by body tissues. Initially, low-magnification
imaging of exposed D. magna sections in the TEM revealed several features, which
suggested absorption of SWCNTs. However, subsequent analysis with additional
techniques (HRTEM, X-ray energy-dispersive spectroscopy and SAD) indicated that
these features were either artifacts produced via the specimen staining process
or consisted of non-graphitic, organic structures. This latter observation
emphasizes the inherent difficulty in resolving SWCNTs embedded within a complex,
organic matrix, as well as the care with which imaging results must be
interpreted and supplemented with other, more analytical techniques.
PMID- 24350829
TI - Downregulation of miR-217 correlates with resistance of Ph(+) leukemia cells to
ABL tyrosine kinase inhibitors.
AB - This study found that long-term exposure of chronic myelogenous leukemia (CML)
K562 cells to BCR/ABL thyrosine kinase inhibitors (TKI) caused drug-resistance in
association with an increase in levels of DNA methyltransferases (DNMT) and a
decrease in levels of microRNA miR-217. These observations are clinically
relevant; an increase in levels of DNMT3A in association with downregulation of
miR-217 were noted in leukemia cells isolated from individuals with BCR/ABL TKI
resistant Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)
ALL) and CML. Further studies with TKI-resistant K562 cells found that forced
expression of miR-217 inhibited expression of DNMT3A through a miR-217-binding
site within the 3'-untranslated region of DNMT3A and sensitized these cells to
growth inhibition mediated by the TKI. Of note, long-term exposure of K562 cells
to dasatinib (10 nM) together with 5-Aza-2'-deoxycytidine (5-AzadC) (0.1 MUM)
potently inhibited proliferation of these cells in association with upregulation
of miR-217 and downregulation of DNMT3A in vitro. In addition, a decrease in
levels of DNMT3A and an increase in levels of miR-217 were noted in K562 tumors
growing in immune-deficient mice that were treated with the combination of 5
AzadC and dasatinib. Taken together, Ph(+) leukemia cells acquire TKI resistance
via downregulation of miR-217 and upregulation of DNMT3A. Inhibition of DNMT3A by
forced expression of miR-217 or 5-AzadC may be useful to prevent drug resistance
in individuals who receive TKI.
PMID- 24350830
TI - Educational inequalities in TV viewing among older adults: a mediation analysis
of ecological factors.
AB - BACKGROUND: Television (TV) viewing, a prevalent leisure-time sedentary behaviour
independently related to negative health outcomes, appears to be higher in less
educated and older adults. In order to tackle the social inequalities, evidence
is needed about the underlying mechanisms of the association between education
and TV viewing. The present purpose was to examine the potential mediating role
of personal, social and physical environmental factors in the relationship
between education and TV viewing among Australian 55-65 year-old adults. METHODS:
In 2010, self-reported data was collected among 4082 adults (47.6% men) across
urban and rural areas of Victoria, for the Wellbeing, Eating and Exercise for a
Long Life (WELL) study. The mediating role of personal (body mass index [BMI],
quality of life), social (social support from family and friends, social
participation at proximal level, and interpersonal trust, social cohesion,
personal safety at distal level) and physical environmental (neighbourhood
aesthetics, neighbourhood physical activity environment, number of televisions)
factors in the association between education and TV viewing time was examined
using the product-of-coefficients test of MacKinnon based on multilevel linear
regression analyses (conducted in 2012). RESULTS: Multiple mediating analyses
showed that BMI (p <= 0.01), personal safety (p < 0.001), neighbourhood
aesthetics (p <= 0.01) and number of televisions (p <= 0.01) partly explained the
educational inequalities in older adult's TV viewing. No proximal social factors
mediated the education-TV viewing association. CONCLUSIONS: Interventions aimed
to reduce TV viewing should focus on personal (BMI) and environmental (personal
safety, neighbourhood aesthetics, number of televisions) factors, in order to
overcome educational inequalities in sedentary behaviour among older adults.
PMID- 24350831
TI - Depressive symptoms and proinflammatory cytokines across the perinatal period in
African American women.
AB - BACKGROUND: Comparatively few studies have examined the biological mechanisms
that may underlie the reported racial disparities in antenatal and postpartum
depression. OBJECTIVE: To examine the associations among race, depressive
symptoms and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis
factor (TNF)-alpha across the perinatal period in a diverse sample of healthy
pregnant women at elevated psychosocial risk. METHODS: 171 subjects were
enrolled. Women were interviewed and blood samples drawn at 18 and 32 weeks
gestation and 6 weeks and 6 months postpartum. Depressive symptoms were measured
using the Edinburgh Postnatal Depression Scale. Serum levels of IL-6 and TNF
alpha were assayed using high sensitivity enzyme-linked immunosorbent assay kits.
RESULTS: Compared with non-African American (AA) women, AA women had
significantly higher levels of IL-6 (est. diff = 0.521, p = 0.02, confidence
interval (CI): 0.088-0.954) but not TNF-alpha across all time points (est. diff =
-0.060, p = 0.80, CI: -0.517 to 0.397). IL-6 was not associated with depressive
symptoms but differences in IL-6 were accounted for by greater Body Mass Index in
AA women. CONCLUSIONS: Compared with non-AA women, AA women entered pregnancy
with elevated inflammatory cytokine levels that persisted across the perinatal
period. This group difference in inflammation did not suggest increased risk for
depression, but suggests other implications for long-term health.
PMID- 24350832
TI - Anti-inflammatory and antioxidative effects of the methanolic extract of the
aerial parts of Mitracarpus frigidus in established animal models.
AB - OBJECTIVES: This study reports the in vivo anti-inflammatory and antioxidative
effects of the methanolic extract of the aerial parts of Mitracarpus frigidus
(MFM) and its chemical fingerprint. METHODS: The acute anti-inflammatory activity
was performed using the carrageenan-induced paw oedema and peritonitis, ear
oedema induced by croton oil and ethyl phenylpropiolate methods. Total COX, COX-1
and COX-2 expression was also evaluated. Chronic activity was determined by
cotton pellet granuloma model. The antioxidative activity was assessed using
liver tissue malondialdehyde, catalase and myeloperoxidase activities. KEY
FINDINGS: M. frigidus showed an intense acute anti-inflammatory action (100 and
300 mg/kg) in a nondose-dependent manner with selective inhibition of COX-2
expression. This activity may be also related to the strong antioxidative effect
observed. By the other side, the chronic anti-inflammatory activity of MFM was
not expressive. Kaempferol, kaempferol-O-rutenoside, rutin, ursolic acid and
psychorubrin were identified in MFM. CONCLUSIONS: The anti-inflammatory activity
of MFM was probably due to inhibition of COX expression in a selective manner for
COX-2. Other mechanisms, such as inhibition of inflammatory mediators and of the
oxidative stress were possibly involved in the effects observed. To the best of
our knowledge, it is the first time those activities are reported for M.
frigidus.
PMID- 24350833
TI - Sudden cardiac death in athletes.
AB - A 'paradox of sport' is that in addition to the undisputed health benefits of
physical activity, vigorous exertion may transiently increase the risk of acute
cardiac events. In general, the risk of sudden cardiac death (SCD) approximately
doubles during physical activity and is 2- to 3-fold higher in athletes compared
to nonathletes. The incidence of SCD in young athletes is in fact very low, at
around 1-3 per 100,000, but attracts much public attention. Variations in
incidence figures may be explained by the methodology used for data collection
and more importantly by differences between subpopulations of athletes. The
incidence of SCD in older (>= 35 years) athletes is higher and may be expected to
rise, as more and older individuals take part in organized sports. SCD is often
the first clinical manifestation of a potentially fatal underlying cardiovascular
disorder and usually occurs in previously asymptomatic athletes. In the young
(<35 years), SCD is mainly due to congenital/inherited cardiac abnormalities,
whilst coronary artery disease (CAD) is the most common cause in older athletes.
Cardiac screening including family/personal history, physical examination and
resting electrocardiogram (ECG) may identify individuals at risk and has the
potential to decrease the risk of SCD in young athletes. Screening including the
ECG has a high sensitivity for underlying disease in young athletes, but the
specificity needs to be improved, whereas the sensitivity of screening without
the use of ECG is very low. The screening modality recommended for young athletes
is of limited value in older athletes, who should receive individualized
screening with cardiac stress testing for patients with high risk of underlying
CAD. As cardiovascular screening will never be able to identify all athletes at
risk, adequate preparedness is vital in case of a potentially fatal event at the
sporting arena/facility. Firstly, we will review the magnitude of the problem of
SCD in athletes of different ages, as well as the aetiology. Secondly, we will
focus on how to prevent SCD in athletes of all ages, reviewing cardiovascular
screening recommendations as well as emergency preparedness and arena safety.
PMID- 24350834
TI - Neuroprotective effect of melatonin against ischemia is partially mediated by
alpha-7 nicotinic receptor modulation and HO-1 overexpression.
AB - Melatonin has been widely studied as a protective agent against oxidative stress.
However, the molecular mechanisms underlying neuroprotection in neurodegeneration
and ischemic stroke are not yet well understood. In this study, we evaluated the
neuroprotective/antioxidant mechanism of action of melatonin in organotypic
hippocampal cultures (OHCs) as well as in photothrombotic stroke model in vivo.
Melatonin (0.1, 1, and 10 MUM) incubated postoxygen and glucose deprivation (OGD)
showed a concentration-dependent protection; maximum protection was achieved at
10 MUM (90% protection). Next, OHCs were exposed to 10 MUM melatonin at different
post-OGD times; the protective effect of melatonin was maintained at 0, 1, and 2
hr post-OGD treatment, but it was lost at 6 hr post-OGD. The protective effect of
melatonin and the reduction in OGD-induced ROS were prevented by luzindole
(melatonin antagonist) and alpha-bungarotoxin (alpha-Bgt, a selective alpha7
nAChR antagonist). In Nrf2 knockout mice, the protective effect of melatonin was
reduced by 40% compared with controls. Melatonin, incubated 0, 1, and 2 hr post
OGD, increased the expression of heme oxygenase-1 (HO-1), and this overexpression
was prevented by luzindole and alpha-bungarotoxin. Finally, administration of 15
mg/kg melatonin following the induction of photothrombotic stroke in vivo,
reduced infarct size (50%), and improved motor skills; this effect was partially
lost in 0.1 mg/kg methyllycaconitine (MLA, selective alpha7 nAChR antagonist)
treated mice. Taken together, these results demonstrate that postincubation of
melatonin provides a protective effect that, at least in part, depends on
nicotinic receptor activation and overexpression of HO-1.
PMID- 24350835
TI - Identification of IgE-binding peptides in hen egg ovalbumin digested in vitro
with human and simulated gastroduodenal fluids.
AB - The digestibility of the major egg allergen ovalbumin (OVA, Gal d 2) with human
and simulated digestive fluids was assessed. Degradation of OVA was faster when
treated with human fluids, particularly following duodenal digestion, leading to
gastrointestinal digests with lower IgE binding. Gastric digestion with both
systems yielded 52 identical cleavage sites and a similar peptide pattern with 47
peptides in common. Subsequent duodenal digestion showed that the human fluid
released fewer and shorter peptides. Several high-frequency IgE-binding epitopes
were detected among the fragments of molecular mass lower than 3 kDa identified
in the digests: OVA (141-154) and OVA (164-176) in the gastrointestinal digests
produced with human fluids; and OVA (125-134), OVA (159-172), OVA (141-154), OVA
(188-198), OVA (326-336), and OVA (370-385) in the gastrointestinal digests
produced with simulated fluids. The high binding frequency of the fragment OVA
(370-385), which reacted with 80% of the sera from allergic patients used, was
noteworthy.
PMID- 24350836
TI - Overcrowding stress decreases macrophage activity and increases Salmonella
Enteritidis invasion in broiler chickens.
AB - Overcrowding stress is a reality in the poultry industry. Chickens exposed to
long-term stressful situations present a reduction of welfare and
immunosuppression. We designed this experiment to analyse the effects from
overcrowding stress of 16 birds/m(2) on performance parameters, serum
corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA
and IgG levels, intestinal integrity, macrophage activity and experimental
Salmonella Enteritidis invasion. The results of this study indicate that
overcrowding stress decreased performance parameters, induced enteritis and
decreased macrophage activity and the relative bursa weight in broiler chickens.
When the chickens were similarly stressed and infected with Salmonella
Enteritidis, there was an increase in feed conversion and a decrease in plasma
IgG levels in the stressed and Salmonella-infected birds. We observed moderate
enteritis throughout the duodenum of chickens stressed and infected with
Salmonella. The overcrowding stress decreased the macrophage phagocytosis
intensity and increased Salmonella Enteritidis counts in the livers of birds
challenged with the pathogenic bacterium. Overcrowding stress via the
hypothalamic-pituitary-adrenal axis that is associated with an increase in
corticosterone and enteritis might influence the quality of the intestinal immune
barrier and the integrity of the small intestine. This effect allowed pathogenic
bacteria to migrate through the intestinal mucosa, resulting in inflammatory
infiltration and decreased nutrient absorption. The data strengthen the
hypothesis that control of the welfare of chickens and avoidance of stress from
overcrowding in poultry production are relevant factors for the maintenance of
intestinal integrity, performance and decreased susceptibility to Salmonella
infection.
PMID- 24350837
TI - Ionic liquid of a gold nanocluster: a versatile matrix for electrochemical
biosensors.
AB - Ionic liquids are room-temperature molten salts that are increasingly used in
electrochemical devices, such as batteries, fuel cells, and sensors, where their
intrinsic ionic conductivity is exploited. Here we demonstrate that combining
anionic, redox-active Au25 clusters with imidazolium cations leads to a stable
ionic liquid possessing both ionic and electronic conductivity. The Au25 ionic
liquid was found to act as a versatile matrix for amperometric enzyme biosensors
toward the detection of glucose. Enzyme electrodes prepared by incorporating
glucose oxidase in the Au25 ionic liquid show high electrocatalytic activity and
substrate affinity. Au25 clusters in the electrode were found to act as effective
redox mediators as well as electronic conductors determining the detection
sensitivity. With the unique electrochemical properties and almost unlimited
structural tunability, the ionic liquids of quantum-sized gold clusters may serve
as versatile matrices for a variety of electrochemical biosensors.
PMID- 24350839
TI - Photochemical intermolecular silylacylations of electron-deficient internal
alkynes.
AB - Light-induced Brook rearrangements of acylsilanes facilitate silylacylation
reactions of electron-deficient internal alkynes. A wide range of aromatic
substituents on the acylsilane aryl group are tolerated, affording a series of
functionalized enonyl silanes. The presence of electron-withdrawing substituents
on the alkyne is crucial for the success of the addition process.
PMID- 24350840
TI - Draft genome sequences of two Bifidobacterium sp. from the honey bee (Apis
mellifera).
AB - BACKGROUND: Widely considered probiotic organisms, Bifidobacteria are common
inhabitants of the alimentary tract of animals including insects. Bifidobacteria
identified from the honey bee are found in larval guts and throughout the
alimentary tract, but attain their greatest abundance in the adult hind gut. To
further understand the role of Bifidobacteria in honey bees, we sequenced two
strains of Bifidobacterium cultured from different alimentary tract environments
and life stages. RESULTS: Reflecting an oxygen-rich niche, both strains possessed
catalase, peroxidase, superoxide-dismutase and respiratory chain enzymes
indicative of oxidative metabolism. The strains show markedly different
carbohydrate processing capabilities, with one possessing auxiliary and key
enzymes of the Entner-Doudoroff pathway. CONCLUSIONS: As a result of long term co
evolution, honey bee associated Bifidobacterium may harbor considerable strain
diversity reflecting adaptation to a variety of different honey bee
microenvironments and hive-mediated vertical transmission between generations.
PMID- 24350841
TI - Cost of anxiety disorders in Japan in 2008: a prevalence-based approach.
AB - BACKGROUND: The societal burden caused by anxiety disorders has likely been
underestimated, while those for schizophrenia and depression have received more
attention. Anxiety disorders represent a significant illness category that occurs
at a high prevalence and poses a considerable burden. However, the cost of
anxiety disorders in Japan has not yet been well researched. The goal of the
present study was to estimate the total cost of anxiety disorders in Japan and to
clarify the characteristics of this burden. METHOD: A prevalence-based approach
was adopted to measure the total cost of anxiety disorders. Anxiety disorders
were defined as diagnosis code F40.0-F41.9 according to the International
Statistical Classification of Diseases and Related Health Problems, 10th
Revision. The cost was comprised of the following components: medical treatment
costs and social service costs as direct costs, and morbidity and mortality costs
as indirect costs. Data were collected from publicly available statistics.
RESULTS: The total cost of anxiety disorders in Japan in 2008 was JPY 2.4
trillion (US$ 20.5 billion at the current exchange rate of US $1 = JPY 116.8).
The direct cost was JPY 50 billion. The morbidity cost was JPY 2.1 trillion,
while the mortality cost was JPY 0.24 trillion. CONCLUSIONS: The social burden
caused by anxiety disorders in Japan is tremendous and is similar to that of
other mental disorders. Productivity loss in the workplace represents the largest
portion of all the cost components. Because the medical examination rate is quite
low, the improvement of healthcare access might contribute to cost mitigation.
PMID- 24350842
TI - The roles of microRNAs in atherosclerosis.
AB - MicroRNA (abbr. miRNA) is an endogenous small non-coding RNAs (containing ~22
nucleotides) found in plants and animals, which functions in transcriptional and
post-transcriptional regulation of gene expression. These endogenous gene
expression inhibitors were primarily described in cancer but recent emerging
roles in the regulation of autoimmune inflammation which is thought to be
associated with cardiovascular diseases (CVDs), including atherosclerosis known
as an autoimmune disease. MiRNA controls innate and adaptive immune responses to
intracellular bacterial infection by targeting interferon-gamma, and plays the
roles in endothelial cell (EC), vascular smooth muscle cell (VSMC), and
macrophages, and thereby leading to regulate the progression of atherosclerosis.
MiRNA modulates several pathways such as lipid uptake and Toll-like receptor
(TLR) signaling, implicating an involvement in plaque development. In the present
review, we focus on the roles of microRNAs in atherosclerosis through which
highlight the therapeutic possibility for the treatment of atherosclerosis.
PMID- 24350843
TI - Molecular dynamics simulation in RNA interference.
AB - RNA interference (RNAi) is a mechanism that utilizes small RNA molecules to
silence gene expression after the gene has been transcribed. To understand the
mechanisms of small RNA biogenesis, target nucleic acid recognition and cleavage,
and how they are influenced by other regulators, one needs to know the structures
and dynamics of the proteins or/and nucleic acids in these processes. Molecular
dynamics (MD) simulation is a powerful tool for understanding motions and
dynamics of macro-biomolecules at an atomic-scale via theoretical and empirical
principles in physical chemistry. With its application to RNAi, an excellent
overview of structural and dynamical mechanistic of RNAi processes has already
emerged. In this review, we summarize the recent advances in MD simulations in
the study of functional modules and their assemblies and target recognition and
cleavage in RNAi processes. Additionally, we also present some perspectives on
this technique.
PMID- 24350844
TI - Indocyanine green: photosensitizer or chromophore? Still a debate.
AB - Indocyanine green (ICG) is a water-soluble anionic tricarbocyanine dye developed
during the Second World War that was first approved for clinical use in humans in
1956. The main features of ICG that make it suitable for bioimaging applications
are its near infrared absorption and its fluorescence. Although ICG is mainly
used for its fluorescence emission properties, it has also been hypothesized that
it can serve as a photosensitizer for photodynamic therapy applications,
eliciting cytotoxic effects both in vitro and in vivo when used in combination
with light at wavelengths in the region of 800-830 nm. Moreover, ICG can be used
for hyperthermia of enhanced-photocoagulation of blood vessels treatment. In this
paper we have gathered all the available data concerning the use of ICG for
different treatments.
PMID- 24350845
TI - Development of small molecule non-peptide formyl peptide receptor (FPR) ligands
and molecular modeling of their recognition.
AB - Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) expressed
on a variety of cell types. These receptors play an important role in the
regulation of inflammatory reactions and sensing cellular damage. They have also
been implicated in the pathogenesis of various diseases, including
neurodegenerative diseases, cataract formation, and atherogenesis. Thus, FPR
ligands, both agonists and antagonists, may represent novel therapeutics for
modulating host defense and innate immunity. A variety of molecules have been
identified as receptor subtype-selective and mixed FPR agonists with potential
therapeutic value during last decade. This review describes our efforts along
with recent advances in the identification, optimization, biological evaluation,
and structure-activity relationship (SAR) analysis of small molecule non-peptide
FPR agonists and antagonists, including chiral molecules. Questions regarding the
interaction at the molecular level of benzimidazoles, pyrazolones, pyridazin
3(2H)-ones, N-phenylureas and other derivatives with FPR1 and FPR2 are discussed.
Application of computational models for virtual screening and design of FPR
ligands is also considered.
PMID- 24350846
TI - Developments in the synthesis and biological activity of glycyl-L-histydyl- L
lysine derivatives.
AB - Three decades of extensive research on biological activity of natural tripeptide
Gly-His-Lys has established the substructure for development of its novel
derivatives which give hope for widening the application in the field of medicine
and dermatology. Synthetic approaches to obtain Gly-His-Lys and its modifications
provide both classical solution method and solid phase peptide synthesis, usage
of different protecting groups and methods of peptide bond formation. In our
present review, we emphasize on the methods of the synthesis described in the
literature and present the aspects of Gly-His-Lys structure modifications that
played a key role in scientific research.
PMID- 24350847
TI - Synergy against fungal pathogens: working together is better than working alone.
AB - Opportunistic fungi are the most important pathogens in modern world. They are
responsible for severe infections in majority of immunocompromised patients.
These microorganisms are commonly present in our environment which is natural
reservoir of new, resistant species. For this reason mycoses are mainly chronic
or long-lasting diseases. Our arsenal of antifungal drugs is growing but still
insufficient for emerging resistant pathogens. An alternative for novel chemical
entity drugs is the multidrug approach. This exploiting the drugs being currently
on market applying simultaneously for better efficacy or to eradicate resistance.
Synergy is the term that describes the phenomenon of increased potency of two or
more drugs administered in combination. In the last decades it gains more
interest and numbers of synergy claimed reports is growing exponentially. However
these have rather low impact on clinical trials or practical use of antimycotics.
In present review we wish to discuss current status of synergy between antifungal
drugs. Both theoretical point of view and practical applicability in clinical
terms are covered. There are serious differences between the assumptions, methods
and interpretations of the results and sometimes even obvious mistakes in the
procedure that was applied or in the outcomes discussed. On the other hands the
specificity of fungal infections introduce dozens of factors affecting the
observed results. Shift form in vitro studies to clinical trials reveals further
difficulties. Hopefully multi-drug approach seems to be effective even if no
strong synergy is displayed.
PMID- 24350848
TI - Development of HIV-1 fusion inhibitors targeting gp41.
AB - The HIV-1 envelope protein glycoprotein 41 (gp41) is crucial in the HIV-1
infection process, therefore gp41 has emerged as an attractive target for drug
design against AIDS. During the past few decades, tremendous efforts have been
made on developing inhibitors that can prevent the HIV-1 entry process via
suppressing functional gp41. In this review, the development of HIV-1 fusion
inhibitors targeting gp41 including peptide inhibitors, small molecule
inhibitors, vaccines and neutralized antibodies will be discussed.
PMID- 24350849
TI - Metabolism of selegiline [(-)-deprenyl)].
AB - Selegiline (1) [(-)-deprenyl] is used to treat patients with Parkinson's disease.
Nevertheless, in much higher doses it has beneficial effects in depression, and
dementia of the aged patients. Selegiline (1) undergoes a complex metabolic
pathway. Its major metabolites include (-)-desmethyldeprenyl (2), (-)
methamphetamine (3) and (-)-amphetamine (4), deprenyl-N-oxide (5) and
formaldehyde (6) as a small metabolic fragment. In addition, more than 40 minor
metabolites of selegiline (1) have also been either detected or proposed by
investigators and researchers. This review analyses the pharmacological activity,
generation pathway and the detection method of the major metabolites of
selegiline (1).
PMID- 24350850
TI - Use of click-chemistry in the development of peptidomimetic enzyme inhibitors.
AB - Cu(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) is often utilized in medicinal
chemistry to make the triazole moiety as it acts as a non-classical bioisostere
of the peptide bond. This useful technique can also be applied in the fragment
based assembly of molecular libraries for high-throughput screening. This
minireview outlines the application of click-chemistry in the synthesis of enzyme
inhibitors with the triazole moiety.
PMID- 24350851
TI - Neuritin, a neurotrophic factor in nervous system physiology.
AB - Neuritin (also known as candidate plasticity gene 15, cpg15) is an activity
induced glycosylphosphatidylinositol- anchored axonal protein and is mainly
expressed in the brain. Neuritin mRNA expression is modulated by neurotrophic
factors, synaptic activity, hormones, sensory experience, and electroconvulsive
seizure therapy. Neuritin has several effects in the nervous system, such as
promoting neurite outgrowth, modulating neurite outgrowth during neuronal
differentiation, protecting motor neuron axons, promoting dendritic growth,
shaping dendritic arbors of target neurons, regulating synaptic plasticity,
stabilizing active synapses, promoting synaptic maturation and neuronal
migration, promoting the development and maturation of visual cortical neurons,
regulating apoptosis of proliferative neurons, and regenerating peripheral nerve
and spinal axons. Neuritin is also implicated in cerebral ischemia, depression,
and cognitive function in schizophrenia, and it upregulates transient outward
K(+) currents in neurons, suggesting that neuritin may be a potential therapeutic
target in peripheral and central nervous system diseases. This review focuses on
the expression, distribution, and physiological functions of neuritin in the
nervous system.
PMID- 24350852
TI - Metal-N-heterocyclic carbene complexes as anti-tumor agents.
AB - It has been a long story of the development of anticancer metallopharmaceuticals
since the identification of cisplatin. Advances in metallodrugs discovery during
the past 40 years have made it an ever-growing area of research in medicinal
inorganic chemistry. Meanwhile, the emerging of N-heterocyclic carbene (NHC)
chemistry has stimulated the newly burgeoning interests in the biomedical
applications of metal-NHC complexes. This review will detail what have been
achieved hitherto in the research of metal-NHC complexes as potential anti-tumor
agents coupled with gold, silver, copper, platinum and palladium. Their mechanism
of action will also be discussed. All the results obtained indicate that this
promising approach is worthy of more focuses and further studies.
PMID- 24350853
TI - Oxidative stress in traumatic brain injury.
AB - Traumatic brain injury (TBI) is a major healthcare concern, constituting a major
cause of death and disability throughout the world. Among the factors leading to
TBI outcome are biochemical cascades which occur in response to primary and
secondary injury. These mechanisms generate oxidative stress, an imbalance
between oxidant and antioxidant agents that can result in neural dysfunction and
death. After TBI, an assembly of oxidative stress markers (carbonylated proteins,
lipid peroxides, reactive oxygen and reactive nitrogen species) are produced in
the brain, while antioxidant defense enzymes decrease (GSH, ratio GSH/GSSG, GPx,
GR, GST, G-6PD, SOD, CAT). This imbalance is directly related to the pathogenesis
of TBI. Therefore, the development of antioxidant strategies is of primary
interest in ongoing efforts to optimize brain injury treatment. The success of
any drug intervention strategy relies, in part, on knowledge of the optimal
dosage and therapeutic window for its administration. But while the enzymes
involved in oxidative stress have been identified, the temporal course of this
imbalance following TBI has yet to be determined. This would explain why most
antioxidant strategies developed to treat patients with TBI have failed.
PMID- 24350854
TI - The proteolytic activation of angiogenic and lymphangiogenic growth factors in
cancer--its potential relevance for therapeutics and diagnostics.
AB - The growth of blood vessels (angiogenesis) and lymphatic vessels
(lymphangiogenesis) in and around solid tumors is central to the growth and
metastatic spread of cancer. The therapeutic targeting of angiogenesis has become
an established modality of cancer treatment, however, more comprehensive
targeting of angiogenic signaling pathways may be required to enhance the
clinical benefits of this approach. Angiogenesis and lymphangiogenesis are
driven, or modulated, by a range of secreted glycoproteins including vascular
endothelial growth factors, platelet-derived growth factors, and transforming
growth factor-beta. These key regulatory growth factors are subject to
proteolytic activation, involving highly specific cleavage events, which can
occur at the cell surface or in the extracellular milieu. These cleavage events
are catalysed by a variety of enzymes including proprotein convertases. This
proteolysis can regulate the activity of these growth factors by enhancing
binding affinities for cell surface receptors and co-receptors, or by altering
their interactions with heparan sulfate proteoglycans, thereby modulating
bioavailability. The proteolytic processing of these growth factors complicates
strategies for targeting them for diagnostic and/or therapeutic purposes in
cancer, as processing can generate various forms with distinct biological
properties. Hence it has been important to determine which forms are biologically
active for promoting angiogenesis and lymphangiogenesis in cancer, so as to
indicate clinical relevance. Here we review the regulation of tumor angiogenesis
and lymphangiogenesis by proteolytic activation of growth factors, and the
potential therapeutic and diagnostic strategies arising from our understanding of
this process.
PMID- 24350855
TI - Trees to treehoppers: genetic variation in host plants contributes to variation
in the mating signals of a plant-feeding insect.
AB - Community genetics research has demonstrated 'bottom-up' effects of genetic
variation within a plant species in shaping the larger community with which it
interacts, such as compositions of arthropod faunas. We demonstrate that such
cross-trophic interactions also influence sexually selected traits. We used a
member of the Enchenopa binotata species complex of treehoppers (Hemiptera:
Membracidae) to ask whether male mating signals are influenced by host plant
genetic variation. We reared a random sample of the treehoppers on potted
replicates of a sample of host plant clone lines. We found that treehopper male
signals varied according to the clone line on which they developed, showing that
genetic variation in host plants affects male treehoppers' behavioural
phenotypes. This is the first demonstration of cross-trophic indirect genetic
effects on a sexually selected trait. We discuss how such effects may play an
important role in the maintenance of variation and within-population phenotypic
differentiation, thereby promoting evolutionary divergence.
PMID- 24350856
TI - Promoting a new generation.
PMID- 24350857
TI - A painful umbilical nodule in a 24-year-old woman. Umbilical endometriosis
(Villar nodule).
PMID- 24350858
TI - Primary multiple miliary osteoma cutis: an unusual Chinese case.
PMID- 24350859
TI - The role of zinc in acne and prevention of resistance: have we missed the "base"
effect?
PMID- 24350860
TI - The role of zinc in rosacea and acne: further reflections.
PMID- 24350862
TI - Local and systemic proteomic changes in medicago truncatula at an early phase of
Sinorhizobium meliloti infection.
AB - A symbiotic association with N-fixing bacteria facilitates the growth of
leguminous plants under nitrogen-limiting conditions. The establishment of the
symbiosis requires signal exchange between the host and the bacterium, which
leads to the formation of root nodules, inside which bacteria are hosted. The
formation of nodules is controlled through local and systemic mechanisms, which
involves root-shoot communication. Our study was aimed at investigating the
proteomic changes occurring in shoots and concomitantly in roots of Medicago
truncatula at an early stage of Sinorhizobium meliloti infection. The principal
systemic effects consisted in alteration of chloroplast proteins, induction of
proteins responsive to biotic stress, and changes in proteins involved in
hormonal signaling and metabolism. The most relevant local effect was the
induction of proteins involved in the utilization of photosynthates and C
consuming processes (such as sucrose synthase and fructose-bisphosphate
aldolase). In addition, some redox enzymes such as peroxiredoxin and ascorbate
peroxidase showed an altered abundance. The analysis of local and systemic
proteome changes suggests the occurrence of a stress response in the shoots and
the precocious alteration of energy metabolism in roots and shoots. Furthermore,
our data indicate the possibility that ABA and ethylene participate in the
communicative network between root and shoot in the control of rhizobial
infection.
PMID- 24350863
TI - Benefits of investment into modern medicines in Central-Eastern European
countries.
AB - Transferability of current evidence and expressing value of innovative
pharmaceuticals according to health system objectives Due to the scarcity of
healthcare resources, decision-makers often expect monetary benefits--including
cost savings or productivity gain--from innovative medicines. Manufacturers try
to fulfill this expectation by expressing the benefits of innovative technologies
in monetary units citing approaches from the scientific literature.
Unfortunately, currently available evidence has limited relevance and
transferability in Central-Eastern European (CEE) countries. This study aims to
summarize how innovative pharmaceuticals in CEE countries may contribute to WHO
defined health system objectives, including health gain, equity in health,
financial protection, responsiveness, equity in finance and financial
sustainability. References in this study are also mainly based on international
examples; therefore, additional policy research from CEE countries is necessary
to validate assumptions. If CEE politicians can rely on credible arguments based
on local research evidence, they may improve long-term strategies and policy
decisions related to healthcare innovation.
PMID- 24350864
TI - Perinatal lamb mortality: an assessment of gross, histological and
immunohistochemical changes in the central nervous system.
AB - AIM: To compare the vascular and neuronal changes in the central nervous system
(CNS) of lambs that died in the first 3 days after birth, from various causes,
with control lambs subject to euthanasia. METHODS: Dead lambs (n=65) were
collected daily during the period 07 September 2010 to 26 September 2010 from a
flock of 200 twin-lamb-bearing ewes. Age-matched lambs from the same flock were
subject to euthanasia as a control group (n=39). Necropsies were conducted on all
study lambs. The cause of death in lambs found dead was categorised as starvation
mismothering-exposure complex (SME), dystocia, or other, based on gross necropsy
findings. Deaths were categorised as SME in lambs with necropsy lesions of
pericardial, perirenal and mesenteric fat catabolism, an empty gastrointestinal
tract and completely inflated lungs. Dystocia was diagnosed by the presence of a
swollen tongue, injected sclera and subcutaneous oedema and haemorrhage around
the head and neck or hind limbs. Deaths were categorised as other if an obvious
cause of death could not be ascertained and if evidence of infection was
identified. The CNS of each lamb necropsied was assessed grossly for haemorrhage,
and using histopathology to determine vascular and neuronal changes.
Immunohistochemistry was performed on selected cases (n=36) to confirm neuronal
death. RESULTS: Of the 65 lambs found dead, 16 (25%) had evidence of cerebral and
spinal meningeal haemorrhage, whereas of the 39 clinically normal control lambs,
all displayed gross evidence of cerebral and spinal meningeal haemorrhage. There
was no evidence of parenchymal vacuolation, neuronal vacuolation or ischaemic
neurons in any of the lamb brain sections including those that died with evidence
of dystocia. There was no difference, within the regions examined, in mean
vascular score between lambs categorised by cause of death (p>0.05). The overall
mean vascular score for the brain stem was greater than the mid brain (p=0.02)
and the cortex (p=0.005) but did not differ from either the spinal cord or
cerebellum (p>0.3). The vascular score for the spinal cord was greater than the
mid brain (p=0.01) and cortex (p=0.003). Lambs that died of dystocia had less
immunoreactivity for microtubule associated protein 2 (MAP2) in the hilus/CA4
region of the hippocampus (p=0.02) and dentate gyrus of the hippocampus (p=0.006)
than those that were subject to euthanasia. CONCLUSIONS: Neither gross nor
histological vascular changes in the CNS could be used to distinguish newborn
lambs that had been subject to euthanasia from those that died with evidence of
SME or dystocia, so meningeal haemorrhages in or on the brain and spinal cord of
lambs that die in the neonatal period cannot be used to support a diagnosis of
birth injury or dystocia. The CA4 region and the dentate gyrus of the hippocampus
are useful regions for detecting hypoxic/ischaemic injury in lambs with evidence
of dystocia. There was no evidence that hypoxia/ischaemia contributed to lambs
dying of SME. CLINICAL RELEVANCE: The results of this study suggest that vascular
changes in the CNS of newborn lambs may be produced artefactually. Caution is
warranted with respect to interpretation of these vascular changes.
PMID- 24350865
TI - Rat hippocampal responses up to 90 days after a single nanoceria dose extends a
hierarchical oxidative stress model for nanoparticle toxicity.
AB - Ceria engineered nanomaterials (ENMs) have very promising commercial and
therapeutic applications. Few reports address the effects of nanoceria in intact
mammals, let alone long term exposure. This knowledge is essential to understand
potential therapeutic applications of nanoceria in relation to its hazard
assessment. The current study elucidates oxidative stress responses in the rat
hippocampus 1 and 20 h, and 1, 7, 30 and 90 days following a single systemic
infusion of 30 nm nanoceria. The results are incorporated into a previously
described hierarchical oxidative stress (HOS) model. During the 1-20 h period,
increases of the GSSG: GSH ratio and cytoprotective phase-II antioxidants were
observed. During the 1-7 d period, cytoprotective phase-II antioxidants
activities were inhibited with concomitant elevation of protein carbonyl (PC), 3
nitrotyrosine (3NT), heme oxygenase-1 (HO-1), cytokine IL-1beta and the autophagy
marker LC-3AB. At 30 day post ceria infusion, oxidative stress had its major
impact. Phase-II enzyme activities were inhibited; concurrently PC, 3NT, HO-1 and
Hsp70 levels were elevated along with augmentation of IL-1beta, pro-apoptotic pro
caspase-3 and LC-3AB levels. This progress of escalating oxidative stress was
reversed at 90 days when phase-II enzyme levels and activities were restored to
normal levels, PC and 3NT levels were reduced to baseline, cytokine and pro
caspase-3 levels were suppressed, and cellular redox balance was restored in the
rat hippocampus. This study demonstrates that a single administration of
nanoceria induced oxidative stress that escalates to 30 days then terminates, in
spite of the previously reported continued presence of nanoceria in peripheral
organs. These results for the first time confirm in vivo the HOS model of
response to ENM previously posited based on in vitro studies and extends this
prior hierarchical oxidative stress model that described three tiers to a 4th
tier, characterized by resolution of the oxidative stress and return to normal
conditions.
PMID- 24350866
TI - Potential sensitivities in frequency modulation and heterodyne amplitude
modulation Kelvin probe force microscopes.
AB - In this paper, the potential sensitivity in Kelvin probe force microscopy (KPFM)
was investigated in frequency modulation (FM) and heterodyne amplitude modulation
(AM) modes. We showed theoretically that the minimum detectable contact potential
difference (CPD) in FM-KPFM is higher than in heterodyne AM-KPFM. We
experimentally confirmed that the signal-to-noise ratio in FM-KPFM is lower than
that in heterodyne AM-KPFM, which is due to the higher minimum detectable CPD
dependence in FM-KPFM. We also compared the corrugations in the local contact
potential difference on the surface of Ge (001), which shows atomic resolution in
heterodyne AM-KPFM. In contrast, atomic resolution cannot be obtained in FM-KPFM
under the same experimental conditions. The higher potential resolution in
heterodyne AM-KPFM was attributed to the lower crosstalk and higher potential
sensitivity between topographic and potential measurements.
PMID- 24350868
TI - Global incidence study.
PMID- 24350867
TI - 5-Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth
factor-induced cell migration through Tiam1 upregulation and Rac1 activation.
AB - Cell migration is an essential step for tumor metastasis. The small GTPase Rac1
plays an important role in cell migration. Previously, we reported that epidermal
growth factor (EGF) induced two waves of Rac1 activation; namely, at 5 min and 12
h after stimulation. A second wave of EGF-induced Rac1 activation was required
for EGF-induced cell migration, however, the spatiotemporal regulation of the
second wave of EGF-induced Rac1 activation remains largely unclear. In this
study, we found that 5-lipoxygenase (5-LOX) is activated in the process of EGF
induced cell migration, and that leukotriene C4 (LTC4 ) produced by 5-LOX
mediated the second wave of Rac1 activation, as well as cell migration.
Furthermore, these effects caused by LTC4 were found to be blocked in the
presence of the antagonist of cysteinyl leukotriene receptor 1 (CysLT1). This
blockage indicates that LTC4 -mediated CysLT1 signaling regulates the second EGF
induced wave of Rac1 activation. We also found that 5-LOX inhibitors, CysLT1
antagonists and the knockdown of CysLT1 inhibited EGF-induced T cell lymphoma
invasion and metastasis-inducing protein 1 (Tiam1) expression. Tiam1 expression
is required for the second wave of EGF-induced Rac1 activation in A431 cells.
Therefore, our results indicate that the 5-LOX/LTC4 /CysLT1 signaling pathway
regulates EGF-induced cell migration by increasing Tiam1 expression, leading to a
second wave of Rac1 activation. Thus, CysLT1 may serve as a new molecular target
for antimetastatic therapy. In addition, the CysLT1 antagonist, montelukast,
which is used clinically for allergy treatment, might have great potential as a
novel type of antimetastatic agent.
PMID- 24350869
TI - The life of Bo K. Siesjo, MD, PhD, 1930-2013.
PMID- 24350870
TI - Global stroke statistics.
AB - In many countries, stroke is a lower priority than other diseases despite its
public health impact. One issue is a lack of readily accessible comparative data
to help make the case for the development of national stroke strategies. To
assist in this process, we need to have a common repository of the latest
published information on the impact of stroke worldwide. We aim to provide a
repository of the most current incidence and mortality data on stroke available
by country and illustrate the gaps in these data. We plan to update this
repository annually and expand the scope to address other aspects of the burden
of stroke. Data were compiled using two approaches: (1) an extensive literature
review with a major focus on published systematic reviews on stroke incidence
(between 1980 and May 14, 2013); and (2) direct acquisition and collation of data
from the World Health Organization to present the most current estimates of
stroke mortality for each country recognized by the World Health Organization.
For mortality, ICD8, ICD9, and ICD10 mortality codes were extracted. Using
population denominators crude stroke mortality was calculated, as well as
adjusting for the World Health Organization world population. We used only the
most recent year reported to the World Health Organization. Incidence rates for
stroke were available for 52 countries, with some countries having incidence
studies undertaken in more than one region. When adjusted to the World Health
Organization world standard population, incidence rates for stroke ranged from 41
per 100 000 population per year in Nigeria (1971-74) to 316/ 100 000/year in
urban Dar-es-Salaam (Tanzania). Some regions had three to fivefold greater
incidence than other countries. Of the 123 countries reporting mortality data,
crude mortality was greatest in Kazhakstan (in 2003). In many regions data were
very old or nonexistent. Such country-level data are important for citizens,
clinicians, and policy makers so that local and global strategies to reduce the
overall burden of stroke can be implemented. Through this first annual review of
country-specific stroke epidemiology, we hope to promote discussion and provide
insights into the worldwide burden of stroke.
PMID- 24350871
TI - Estimating the annual number of strokes and the issue of imperfect data: an
example from Australia.
AB - BACKGROUND: Estimates of strokes in Australia are typically obtained using 1996
1997 age-specific attack rates from the pilot North East Melbourne Stroke
Incidence (NEMESIS) Study (eight postcode regions). Declining hospitalizations
for stroke indicate the potential to overestimate cases. AIMS: To illustrate how
current methods may potentially overestimate the number of strokes in Australia.
METHODS: Hospital separations data (primary discharge ICD10 codes I60 to I64) and
three stroke projection models were compared. Each model had age- and gender
specific attack rates from the NEMESIS study applied to the 2003 population. One
model used the 2003 Burden of Disease approach where the ratio of the 1996-1997
NEMESIS study incidence to hospital separation rate in the same year was adjusted
by the 2002/2003 hospital separation rate within the same geographic region using
relevant ICD-primary diagnosis codes. Hospital separations data were inflated by
12.1% to account for nonhospitalized stroke, while the Burden of Disease model
was inflated by 27.6% to account for recurrent stroke events in that year. The
third model used 1997-1999 attack rates from the larger 22-postcode NEMESIS study
region. RESULTS: In 2003, Australian hospitalizations for stroke (I60 to I64)
were 33,022, and extrapolation to all stroke (hospitalized and nonhospitalized)
was 37,568. Applying NEMESIS study attack rates to the 2003 Australian
population, 50,731 strokes were projected. Fewer cases for 2003 were estimated
with the Burden of Disease model (28,364) and 22-postcode NEMESIS study rates
(41,332). CONCLUSIONS: Estimating the number of strokes in a country can be
highly variable depending on the recency of data, the type of data available, and
the methods used.
PMID- 24350872
TI - INTERACT2: a reason for optimism with spontaneous intracerebral hemorrhage?
AB - The first Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage
Trial (INTERACT1) study found that early intensive BP lowering seemed to
attenuate haematoma growth when compared with a more conservative guideline based
policy. Clinicians were therefore waiting with anticipation for the results of
INTERACT2, in which 2839 patients with spontaneous ICH and a systolic BP between
150 and 220 mmHg were randomly assigned to receive intensive anti-hypertensive
therapy with a systolic target of <140 mmHg within one hour, or a standard
guideline recommended treatment of <180 mmHg. INTERACT2 failed to show a
significant reduction in the rate of the primary outcome of death or major
disability [modified Rankin scale score (mRS) of 3-6], with early intensive BP
lowering. However, in the key secondary endpoint of an ordinal analysis of the
distribution of mRS scores, there was a significant favorable shift in those
patients with aggressive therapy. There were also more patients who were normal
or near normal (mRS of 0-1) at 90 days. Reassuringly, there were no differences
in the rate of death or numbers of serious adverse events between the two groups.
INTERACT2 has shown that a strategy of early and aggressive BP lowering is safe
in a wide range of clinical settings, and is probably effective. The
Antihypertensive Treatment of Acute Cerebral Haemorrhage (ATACH) II trial, which
is using similar BP targets to INTERACT, should shed further light on the benefit
of early aggressive BP lowering in patients with spontaneous ICH.
PMID- 24350873
TI - Cochrane Stroke Group: twenty years of evidence-based stroke medicine.
AB - The Cochrane Stroke Group was one of the first specialist review groups set up
within The Cochrane Collaboration and has been in existence for 20 years. Its key
outputs include a number of high profile reviews in the area of the management of
stroke, which have become one of the most important sources of information for
clinical practice guidelines. The work of the group is only possible through a
collaborative network of staff, editors, and authors.
PMID- 24350874
TI - The high rate of major depression after stroke in Nigeria may be the result of
high cumulative morbidity burden: a call for greater efficiency in the management
of stroke in developing countries.
PMID- 24350875
TI - Differentiation of a symptomatic cerebral microbleed from silent microbleeds.
PMID- 24350876
TI - A nationwide plan for postacute care of stroke in Taiwan.
PMID- 24350878
TI - Sacroiliac joint dysfunction as a reason for the development of acetabular
retroversion: a new theory.
AB - Acetabular retroversion has been recently implicated as an important factor in
the development of femoral acetabular impingement and hip osteoarthritis. The
proper function of the hip joint requires that the anatomic features of the
acetabulum and femoral head complement one another. In acetabular retroversion,
the alignment of the acetabulum is altered where it opens in a posterolaterally
instead of anterior direction. Changes in acetabular orientation can occur with
alterations in pelvic tilt (anterior/posterior), and pelvic rotation
(left/right). An overlooked problem that alters pelvic tilt and rotation, often
seen by physical therapists, is sacroiliac joint dysfunction. A unique feature
that develops in patients with sacroiliac joint dysfunction (SIJD) is asymmetry
between the left and right innominate bones that can alter pelvic tilt and
rotation. This article puts forth a theory suggesting that acetabular
retroversion may be produced by sacroiliac joint dysfunction.
PMID- 24350877
TI - Adapting community based participatory research (CBPR) methods to the
implementation of an asthma shared decision making intervention in ambulatory
practices.
AB - OBJECTIVE: Translating research findings into clinical practice is a major
challenge to improve the quality of healthcare delivery. Shared decision making
(SDM) has been shown to be effective and has not yet been widely adopted by
health providers. This paper describes the participatory approach used to adapt
and implement an evidence-based asthma SDM intervention into primary care
practices. METHODS: A participatory research approach was initiated through
partnership development between practice staff and researchers. The collaborative
team worked together to adapt and implement a SDM toolkit. Using the RE-AIM
framework and qualitative analysis, we evaluated both the implementation of the
intervention into clinical practice, and the level of partnership that was
established. Analysis included the number of adopting clinics and providers, the
patients' perception of the SDM approach, and the number of clinics willing to
sustain the intervention delivery after 1 year. RESULTS: All six clinics and
physician champions implemented the intervention using half-day dedicated asthma
clinics while 16% of all providers within the practices have participated in the
intervention. Themes from the focus groups included the importance of being part
the development process, belief that the intervention would benefit patients, and
concerns around sustainability and productivity. One year after initiation, 100%
of clinics have sustained the intervention, and 90% of participating patients
reported a shared decision experience. CONCLUSIONS: Use of a participatory
research process was central to the successful implementation of a SDM
intervention in multiple practices with diverse patient populations.
PMID- 24350879
TI - ITO@Cu2S tunnel junction nanowire arrays as efficient counter electrode for
quantum-dot-sensitized solar cells.
AB - Quantum-dot-sensitized solar cell (QDSSC) has been considered as an alternative
to new generation photovoltaics, but it still presents very low power conversion
efficiency. Besides the continuous effort on improving photoanodes and
electrolytes, the focused investigation on charge transfer at interfaces and the
rational design for counter electrodes (CEs) are recently receiving much
attention. Herein, core-shell nanowire arrays with tin-doped indium oxide (ITO)
nanowire core and Cu2S nanocrystal shell (ITO@Cu2S) were dedicatedly designed and
fabricated as new efficient CEs for QDSSCs in order to improve charge collection
and transport and to avoid the intrinsic issue of copper dissolution in popular
and most efficient Cu/Cu2S CEs. The high-quality tunnel junctions formed between
n-type ITO nanowires and p-type Cu2S nanocrystals led to the considerable
decrease in sheet resistance and charge transfer resistance and thus facilitated
the electron transport during the operation of QDSSCs. The three-dimensional
structure of nanowire arrays provided high surface area for more active catalytic
sites and easy accessibility for an electrolyte. As a result, the power
conversion efficiency of QDSSCs with the designed ITO@Cu2S CEs increased by 84.5
and 33.5% compared to that with planar Au and Cu2S CEs, respectively.
PMID- 24350882
TI - I2-catalyzed synthesis of substituted pyrroles from alpha-amino carbonyl
compounds and aldehydes.
AB - A direct method for the synthesis of 1,3,4-triarylpyrroles was achieved easily
from cyclization of alpha-amino carbonyl compounds and aldehydes catalyzed by I2.
Various substituted groups can be employed, and this reaction can proceed
smoothly in moderate to good yields.
PMID- 24350883
TI - Antiviral effects of mulberry (Morus alba) juice and its fractions on foodborne
viral surrogates.
AB - Norovirus infection is a major cause of nonbacterial foodborne outbreaks
worldwide, but no specific treatments are available yet. In this study, we
investigated the antiviral activity of mulberry (Morus alba, Ma) juice and its
fractions on murine norovirus-1 (MNV-1) and feline calicivirus-F9 (FCV-F9) as
human norovirus surrogates using cytopathic effect inhibition, plaque reduction,
and RNA expression assays. In time-of-addition experiments, Ma juice was found to
be effective in reducing the infectivity of MNV-1 and FCV-F9 in the pre- and co
treatments. The effective concentration for 50% reduction was approximately
0.005% juice (relative to 100% natural juice) and 0.25% juice for MNV-1 and FCV
F9, respectively. Ma juice at 0.1% exhibited about 60% reduction of the MNV-1
polymerase gene expression, confirming the inhibition of viral replication. In an
attempt to identify active components with antiviral activities, Ma-F1 (<3 kDa)
and Ma-F2 (>3 kDa) were examined to show that Ma-F2 was more effective than Ma-F1
in all modes, except for pre-virus treatment. Nevertheless, two major
polyphenolic compounds of Ma juice, cyanidin-3-glucoside and cyanidin-3
rutinoside, showed antiviral activity in the co-treatment mode. Our results
suggest that Ma juice and its fractions may inhibit internalization and
replication of MNV-1, whereas it may influence adherence or internalization of
FCV-F9 virions. Ma juice may prove useful in the prevention of foodborne viral
infection.
PMID- 24350884
TI - Effect of composition in the development of carbamazepine hot-melt extruded solid
dispersions by application of mixture experimental design.
AB - OBJECTIVES: This study investigates the application of hot-melt extrusion for the
formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol
polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF,
Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In
agreement with the current Quality by Design principle, formulations of solid
dispersions were prepared according to a D-optimal mixture experimental design,
and the influence of formulation composition on the properties of the dispersions
(CBZ heat of fusion and release rate) was estimated. METHODS: Prepared solid
dispersions were characterized using differential scanning calorimetry,
attenuated total reflectance infrared spectroscopy and hot stage microscopy, as
well as by determination of the dissolution rate of CBZ from the hot-melt
extrudates. KEY FINDINGS: Solid dispersions of CBZ can be successfully prepared
using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer
facilitated the processing and decreased the hardness of hot-melt extrudates.
Regardless of their composition, all hot-melt extrudates displayed an improvement
in the release rate compared to the pure CBZ, with formulations having the ratio
of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate.
CONCLUSIONS: Interactions between the mixture components (CBZ and polymers), or
quadratic effects of the components, play a significant role in overall influence
on the CBZ release rate.
PMID- 24350885
TI - Single-nanoparticle near-infrared surface plasmon resonance microscopy for real
time measurements of DNA hybridization adsorption.
AB - A novel 814 nm near-infrared surface plasmon resonance (SPR) microscope is used
for the real-time detection of the sequence-selective hybridization adsorption of
single DNA-functionalized gold nanoparticles. The objective-coupled, high
numerical aperture SPR microscope is capable of imaging in situ the adsorption of
single polystyrene and gold particles with diameters ranging from 450 to 20 nm
onto a 90 MUm * 70 MUm area of a gold thin film with a time resolution of
approximately 1-3 s. Initial real-time SPR imaging (SPRI) measurements were
performed to detect the accumulation of 40 nm gold nanoparticles for 10 min onto
a gold thin film functionalized with a 100% complementary DNA surface at
concentrations from 5 pM to 100 fM by counting individual particle binding
events. A 100% noncomplementary DNA surface exhibited virtually no nanoparticle
adsorption. In contrast, in a second set of SPRI measurements, two component
complementary/noncomplementary mixed DNA monolayers that contained a very small
percentage of complementary sequences ranging from 0.1 to 0.001%, showed both
permanent and transient hybridization adsorption of the gold nanoparticles that
could be tracked both temporally and spatially with the SPR microscope. These
experiments demonstrate that SPR imaging measurements of single biofunctionalized
nanoparticles can be incorporated into bioaffinity biosensing methods at
subpicomolar concentrations.
PMID- 24350886
TI - Optimising outcome assessment to improve quality and efficiency of stroke trials.
AB - Substantial progress has been made in treatment of stroke and much of this has
been driven by large scale, multi-centre, randomised controlled trials. Although
stroke is a frequent cause of mortality, stroke-related disability and functional
decline is of equal or greater concern to patients and carers. Thus, to prove
efficacy of an intervention for stroke, we need robust methods of describing
recovery. Various functional assessment scales are available, the tool
recommended as trial end point by many specialist societies and regulatory
authorities is the modified Rankin Scale (mRS). We will use the mRS as exemplar
to discuss contemporary research around functional assessment for stroke trials,
including recent work around structured assessments, assessor training and end
point adjudication panels. We will present an overview and critique of these
studies and give examples where strategies to improve mRS assessment are
impacting on the quality of stroke clinical trials.
PMID- 24350887
TI - Paying the price: a cross-sectional survey of Australian socioeconomically
disadvantaged smokers' responses to hypothetical cigarette price rises.
AB - INTRODUCTION AND AIMS: Increases in tobacco taxation can lead to reductions in
tobacco consumption and prevalence of use across social groups. However, use of
price-minimisation strategies to manage current and future tobacco use and the
role of financial stress is less understood. This study aimed to measure the
effect of cigarette price increases on price-minimisation strategy endorsement
and financial stress among socioeconomically disadvantaged smokers. DESIGN AND
METHODS: Community service organisation welfare recipients in NSW, Australia
completed a touchscreen survey. Smoking history, financial stress, highest price
to quit and responses to hypothetical cigarette price increases were assessed.
RESULTS: Participants were 354 smokers (response rate = 79%). Most participants
received income from a government pension (95%), earned G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099-2408G> A
(rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic
subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase
chain reaction combined with the restriction fragment length polymorphism (PCR
RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC)
for Adverse Events v.3.0 scale. The population was divided into the CTC0-2 group
(CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and
above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using
the multivariate logistic regression analysis. RESULTS: A significant difference
in Ku70 c.1781G> T genotype distribution was observed between the CTC0-2 and CTC3
+ groups for the 120 patients analyzed. The GG carriers were at higher risks for
severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287
6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80
(c.2099-2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development
of severe oral mucositis. Stratification analyses for the 50 patients treated
with radiation alone further confirmed the association between the variant
genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183-22.238, p = 0.029).
Concurrent radiochemotherapy increased the risk of severe OM for both the TT
homozygotes and GG genotypes. CONCLUSIONS: Our study suggests that the Ku70
c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral
mucositis in Chinese nasopharyngeal carcinoma patients.
PMID- 24350918
TI - Abscopal effect of radiation therapy: Interplay between radiation dose and p53
status.
AB - PURPOSE: This study investigates whether the abscopal effect induced by radiation
therapy (RT) is able to sterilize non-irradiated tumour cells through bystander
signals. MATERIAL AND METHODS: Wild-type (wt)-p53 or p53-null HCT116 human colon
cancer cells were xenografted into both flanks of athymic female nude mice. When
tumours reached a volume of 0.2 cm(3), irradiation was performed, under strict
dose monitoring, with a dedicated mobile accelerator designed for intra-Operative
RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron
beam, was delivered to a tumour established in one side flank, leaving the other
non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry
out short-term molecular analyses. RESULTS: All directly-irradiated tumours,
showed a dose-dependent delayed and reduced regrowth, independent of the p53
status. Importantly, a significant effect on tumour-growth inhibition was also
demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a
moderate effect also evident after 10 Gy-irradiation. In contrast, no significant
difference was observed in the NIR p53-null tumours, independent of the dose
delivered. Molecular analyses indicate that p53-dependent signals might be
responsible for the abscopal effect in our model system, via a pro-apoptotic
pathway. CONCLUSIONS: We suggest that the interplay between delivered dose and
p53 status might help to sterilize out-of-field tumour cells.
PMID- 24350919
TI - Proteomics of cancer stem cells.
AB - PURPOSE: New understanding of cancer stem cell (CSC) biology continues to emerge
due to development of novel methods in genomics and proteomics. Analysis of
nucleic acids (RNA, DNA) is widely used to elucidate molecular perturbations in
malignant tumors and carcinoma cells, however genome data do not reflect the
functional activities of encoded proteins. Therefore proteome-based methods could
enhance knowledge about deregulation of pathways as a result of altered
expression and activities of proteins in CSC. METHODS AND RESULTS: A sufficient
number of CSC for proteomic analyses can be obtained in a variety of ways:
Fluorescence (FACS) and magnetic (MACS) activated cell sorting, laser cell
capture microdissection, and three-dimensional spheroid/organoid cell culture.
These methods to enrich and isolate CSC can be performed either with or without
staining using antibodies against currently known CSC-specific cell surface
molecules, such as clusters of differentiation 44, 24, 133 (CD44, CD24, CD133),
epithelial cell adhesion molecule (EpCAM), aldehyde-dehydrogenase-1 (ALDH1), etc.
The most important limitation on using antibody-based staining of CSC is that we
still do not possess definitive CSC surface markers. This review article
discusses methods that could be used to study protein profiling of CSC and to
identify novel CSC-specific biomarkers and therapeutic targets. CONCLUSION:
Despite an opinion that the proteomic approach is time-consuming, laborious and
difficult, this method can be used effectively to clarify which pathways are
involved in regulating various intratumoral processes, including activation of
CSC. Based on this point of view, searching and identification of single
molecules as biomarkers or therapeutic targets could become possible when CSC
associated pathways are well described and clearly understood due to detailed
investigation of the protein patterns in pre-clinical models and clinical
samples.
PMID- 24350920
TI - Cofilin-1 overexpression and its role in tumor growth and progression in systemic
malignancies.
PMID- 24350921
TI - Design, synthesis, and anti-tumor activity of novel betulinic acid derivatives.
AB - Seventeen new derivatives of betulinic acid (BA) with potential anti-tumor
activity have been synthesized. In order to improve the bioactivity of BA, we
connected BA and nitric oxide donors together via different linkers. The results
of the biological activity of these derivatives showed that four compounds
exhibited obvious cytotoxicity against human hepatocellular carcinoma cells in
vitro.
PMID- 24350922
TI - Prevalence of metabolic syndrome in Brazilian adults: a systematic review.
AB - BACKGROUND: The metabolic syndrome (MS) is a complex of risk factors for
cardiovascular disease. This syndrome increases the risk of diabetes,
cardiovascular disease and all-cause mortality. It has been demonstrated that the
prevalence of MS is increasing worldwide. Despite the importance of MS in the
context of metabolic and cardiovascular disease, few studies have described the
prevalence of MS and its determinants in Latin America. The present study aims to
assess studies describing the prevalence of MS in Brazil in order to determine
the global prevalence of the syndrome and its components. METHODS: Systematic
review. Searches were carried out in PubMed and Scielo from the earliest
available online indexing year through May 2013. There were no restrictions on
language. The search terms used to describe MS were taken from the PubMed (MeSH)
dictionary: "metabolic syndrome x", "prevalence" and "Brazil". Studies were
included if they were cross-sectional, described the prevalence of MS and were
conducted in apparently healthy subjects, from the general population, 19-64
years old (adult and middle aged) of both genders. The titles and abstracts of
all the articles identified were screened for eligibility. RESULTS: Ten cross
sectional studies were selected. The weighted mean for general prevalence of MS
in Brazil was 29.6% (range: 14.9%-65.3%). Half of the studies used the criteria
for clinical diagnosis of MS proposed by the National Cholesterol Education
Program Adult Treatment Panel III (NCEP-ATP III) (2001). The highest prevalence
of MS (65.3%) was found in a study conducted in an indigenous population, whereas
the lowest prevalence of MS (14.9%) was reported in a rural area. The most
frequent MS components were low HDL-cholesterol (59.3%) and hypertension (52.5%).
CONCLUSIONS: Despite methodological differences among the studies selected, our
findings suggested a high prevalence of MS in the Brazilian adult population.
PMID- 24350923
TI - Allogeneic adipose stem cell therapy in acute myocardial infarction.
AB - BACKGROUND: Stem cell therapy offers a promising approach to reduce the long-term
mortality rate associated with heart failure after acute myocardial infarction
(AMI). To date, in vivo translational studies have not yet fully studied the
immune response to allogeneic adipose tissue-derived mesenchymal stem cells
(ATMSCs). We analysed the immune response and the histological and functional
effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine
the effect of administration timing. DESIGN: Pigs that survived AMI (24/26)
received intracoronary administration of culture medium after reperfusion (n =
6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or
ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function,
alloantibodies and histological analysis were evaluated. RESULTS: Administration
of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of
cell engraftment; some of those cells expressed endothelial, smooth muscle and
cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion
compared with that performed at 7 days was more effective in increasing: vascular
density (249 +/- 64 vs. 161 +/- 37 vessels/mm2; P < 0.01), T lymphocytes (1 +/-
0.4 vs. 0.4 +/- 0.3% of area CD3(+) ; P < 0.05) and expression of vascular
endothelial growth factor (VEGF; 32 +/- 7% vs. 20 +/- 4% of area VEGF(+) ; P <
0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but
generated alloantibodies. CONCLUSIONS: The present study is the first to
demonstrate that allogeneic ATMSCs elicit an immune response and, when
administered immediately after reperfusion, are more effective in increasing VEGF
expression and neovascularization.
PMID- 24350924
TI - Centenarian offspring: a model for understanding longevity.
AB - A main objective of current medical research is to improve the life quality of
elderly people as priority of the continuous increase of ageing population. This
phenomenon implies several medical, economic and social problems because of
dramatic increase in number of non autonomous individuals affected by various
pathologies. Accordingly, the research interest is focused on understanding the
biological mechanisms involved in determining the positive ageing phenotype, i.e.
the centenarian phenotype. In achieving this goal the choice of an appropriate
study models is fundamental. Centenarians have been used as an optimal model for
successful ageing. However, this model shows several limitations, i.e. the
selection of appropriate controls and the use itself of the centenarians as a
suitable model for healthy ageing. Thus, the interest has been centered on
centenarian offspring, healthy elderly people. They may represent a model for
understanding exceptional longevity for the following reasons: they exhibit a
protective genetic background, cardiovascular and immunological profile, as well
as a reduced rate of cognitive decline than age-matched people without
centenarian relatives. Several of these aspects are summarized in this review
based on the literature and the results of our studies.
PMID- 24350925
TI - Telomeres and their role in aging and longevity.
AB - Telomeres are DNA-protein structures that form protective caps at the end of
eukaryotic chromosomes. They constitute the safeguards of chromosome degradation
and are responsible for maintaining genomic integrity. The multifactorial nature
of telomere length (TL) regulation increases the perplexity of studies in the
field. TL is characterized by a high variability among individuals (birth and
later life) and among species but it is unknown whether this is associated with
their lifespan potential. TL is also highly heritable, longer in women than in
men; it is highly variable between tissues and organs and inversely related to
chronological age. Accelerated telomere loss has been associated with many
chronic diseases of aging. Premature aging or cellular senescence, seen in early
life, through increased oxidative stress and DNA damage to telomeric ends may be
initiators of processes related to these diseases. During the recent decade,
research around telomere biology has rapidly expanded due to its dynamic
involvement in aging and longevity. However, longevity is not necessarily an
indication of disability-free aging. There is substantial scientific disagreement
and controversial results, regarding even the basic nature of aging and the path
to longevity. We review the current evidence linking telomere biology to aging
processes and mechanisms leading to longevity.
PMID- 24350926
TI - Mediterranean diet and longevity: an example of nutraceuticals?
AB - The Mediterranean diet (Mediet) is an eating pattern characterizing a lifestyle
and culture that has been reported to contribute to better health and quality of
life. The Mediet reflects food patterns typical of Mediterranean regions, where
olive oil plays an essential role in the food pyramid. Olive oil is located in
the middle and it is considered the principal source of dietary fat because of
its high nutritional quality (particularly extra virgin olive oil). Several
studies have shown the effect of the Mediet on healthy status by lowering the
rates of coronary heart disease, certain cancers, and some other age-related
chronic diseases. Although the scientific literature regarding diet and life span
is complex and with different opinions, there are studies that demonstrate the
beneficial effects of the Mediet on longevity. Therefore, the Mediet may be
considered as including several nutraceuticals that favourably influence health.
In the present review we discuss two Mediterranean populations from the island of
Ikaria (Greece) and the Sicani Mounts (Sicily, Italy) whose longevity is
attributed to a close adherence to the Mediet.
PMID- 24350927
TI - Genes of human longevity: an endless quest?
AB - Human longevity is a complex trait in which genetics, epigenetics, environmental
and stochasticity differently contribute. To disentangle the complexity, our
studies on genetics of longevity were, at the beginning, mainly focused on the
extreme phenotypes, i.e. centenarians who escaped the major age-related diseases
compared with cross sectional cohorts. Recently, we implemented this model by
studying centenarians' offspring and offspring of non-long lived parents. In
association, during studies on many candidate genes SNPs, positively or
negatively correlated with longevity have been identified. The results obtained
on Insulin-like Growth Factor 1 Receptor (IGF1R) polymorphisms showed a
correlation between specific genetic variants combinations and the low plasma
level of IGF1 in centenarians, suggesting an impact of the IGF-I/insulin pathway
on human longevity. This pathway together with mammalian target of rapamycin
(mTOR) will be reviewed as being the most promising for longevity. Further, we
will summarise the role of apolipoprotein E (APOE) variants in human longevity
since the results of the large European project GEHA (Genetics of Healthy Aging)
indicate APOE among the chromosomal loci associated with longevity. On the other
hand, the identification of longevity-related genes does not explain the
mechanisms of healthy aging and longevity rather pose questions on epigenetic
contribution, gene regulation and the interactions with essential genomes, i.e.
mitochondrial DNA and microbiota. To fully disentangle what appears to be an
endless quest, all the components of the complexity of human longevity genetics
are taken into account.
PMID- 24350929
TI - Ageing, longevity, exceptional longevity and related genetic and non genetics
markers: panel statement.
AB - In May 2012, a group of scientists and clinicians met in Athens (Greece) to
consider the relevance of ageing, longevity, exceptional longevity and related
genetic and non genetic markers. During this meeting, we firstly reviewed recent
epidemiological and clinical studies on ageing, longevity and exceptional
longevity, briefly analyzed the ageing theories and discussed successful and
unsuccessful ageing also taking into account the evolutionary perspective.
Secondly, we considered the three phenotypes based on the definition of ageing,
longevity and exceptional longevity and the associated biomarkers. Third, we
discussed proposed treatments suitable to counteract or slow down ageing.
Finally, this panel produced a consensus statement to highlight the importance of
ageing, longevity and exceptional longevity, since this is a rapidly increasing
phenotype worldwide. We acknowledge that not all experts in this field may
completely agree with this statement.
PMID- 24350928
TI - Phenotypes and genotypes of high density lipoprotein cholesterol in exceptional
longevity.
AB - A change in the lipoprotein profile is a metabolic hallmark of aging and has been
the target for modern medical developments. Although pharmaceutical interventions
aimed at lipid lowering substantially decrease the risk of cardiovascular
disease, they have much less impact on mortality and longevity. Moreover, they
have not affected death from other age-related diseases. In this review we focus
on high density lipoprotein (HDL) cholesterol, the levels of which are either
elevated or do not decrease as would be expected with aging in centenarians, and
which are associated with lower prevalence of numerous age-related diseases;
thereby, suggesting a potential HDL-mediated mechanism for extended survival. We
also provide an update on the progress of identifying longevity-mediating lipid
genes, describe approaches to discover longevity genes, and discuss possible
limitations. Implicating lipid genes in exceptional longevity may lead to drug
therapies that prevent several age-related diseases, with such efforts already on
the way.
PMID- 24350930
TI - The challenges in moving from ageing to successful longevity.
AB - During the last decades survival has significantly improved and centenarians are
becoming a fast-growing group of the population. Human life span is mainly
dependent on environmental and genetic factors. Favourable modifications of
lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare
(e.g. effective vascular disease prevention) have also increased human life span.
Genetic factors contribute to the variation of human life span by around 25%,
which is believed to be more profound after 85 years of age. It is likely that
multiple factors influence life span and we need answers to questions such as: 1)
What does it take to reach 100?, 2) Do centenarians have better health during
their lifespan compared with contemporaries who died at a younger age?, 3) Do
centenarians have protective modifications of body composition, fat distribution
and energy expenditure, maintain high physical and cognitive function, and
sustained engagement in social and productive activities?, 4) Do centenarians
have genes which contribute to longevity?, 5) Do centenarians benefit from
epigenetic phenomena?, 6) Is it possible to influence the transgenerational
epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the
influence of nutrigenomics important for longevity?, 8) Do centenarians benefit
more from drug treatment, particularly in primary prevention?, and, 9) Are there
any potential goals for drug research? Many definitions of successful ageing have
been proposed, but at present there is no consensus definition. Such definitions
may need to differentiate between "Longevity Syndrome" and "Exceptional
Longevity".
PMID- 24350931
TI - Ageing mechanisms and associated lipid changes.
AB - Ageing is related to slowdown/breakdown of the somatotropic axis (i.e. the
somatopause) leading to many physiological changes. The somatopause is
accompanied by DNA and other macromolecule damage, and is characterized by a
progressive decline in vitality and tissue function. We still do not have a
definitive understanding of the mechanism( s) of ageing. Several overlapping
theories have been proposed such as: 1) The free radical theory, 2) Mitochondrial
Ageing, 3) The Glycation Theory, 4) Protein Damage and Maintenance in Ageing,
and, 5) DNA Damage and Repair. Furthermore, several models of ageing were
introduced such as genetically programmed senescence, telomere shortening,
genomic instability, heterochromatin loss, altered epigenetic patterns and long
lived cells. There are certain lipid modifications associated with the
somatopause, characterized mainly by an increase in total cholesterol and
triglyceride levels in both genders. In this review we consider the mechanisms of
ageing and the associated changes in lipid metabolism according to gender.
PMID- 24350932
TI - Cellular senescence in ageing, age-related disease and longevity.
AB - Cellular senescence is the state of permanent inhibition of cell proliferation.
Senescent cells are characterized by several features including increased
activity of senescence-associated beta-galactosidase (SA-beta-GAL) and
senescenceassociated secretory phenotype (SASP). In vitro, 2 types of senescence
have been described. One is telomere-dependent replicative senescence and the
second is stress-induced premature senescence (SIPS). Despite some tissue
specific characteristics many kinds of cells, including stem/progenitor cells,
can undergo senescence both in vitro and in vivo. Senescent cells were detected
in murine, primate and human tissues using different markers. There is mounting
evidence that senescent cells contribute to ageing and age-related disease by
generating a low grade inflammation state (senescenceassociated secretory
phenotype-SASP). Even though cellular senescence is a barrier for cancer it can,
paradoxically, stimulate development of cancer via proinflammatory cytokines.
There is evidence that senescent vascular cells, both endothelial and smooth
muscle cells, participate in atherosclerosis and senescent preadipocytes and
adipocytes have been shown to lead to insulin resistance. Thus, modulation of
cellular senescence is considered as a potential pro-longevity strategy. This can
be achieved by: elimination of selected senescent cells, epigenetic reprogramming
of senescent cells, preventing cellular senescence or influencing the secretory
phenotype. Some pharmacological interventions have already shown promising
results.
PMID- 24350933
TI - Association between genetic variations in the insulin/insulin-like growth factor
(Igf-1) signaling pathway and longevity: a systematic review and meta-analysis.
AB - Some studies have shown that polymorphisms in the insulin growth factor-1 (IGF-1)
signaling pathway genes could influence human longevity. However, the results of
different studies are often inconsistent. Our aim was to investigate by
systematic review and meta-analysis the association of the common polymorphisms
defining the genetic variability of the IGF-1 signaling pathway associated with
human longevity. Eleven studies investigating the association between the
polymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor (IGF
1R), Forkhead box O3A (FOXO3A) and Silent mating type Information Regulation 1
(SIRT1) and longevity were found and analyzed. The modelfree approach was applied
to meta-analyze these studies. No association was reported between the single
nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the only available
study. The meta-analysis of available data from four studies, showed a
significant association with the IGF-1R polymorphism rs2229765, suggesting that
subjects with the Abearing genotype have a greater chance of longevity.
Concerning the five studies on FOXO3A SNPs, for the rs2764264 a significant
association with longevity was observed for C allele when only males were
included in the analysis. Statistically significant results were obtained for
other SNPs as well, i.e. rs2802292 (G allele), rs9400239 and rs479744 (T and A
alleles, respectively). For rs9400239 the association was observed in long lived
males with a lower odds ratio than in centenarians, while in rs479744 a
significant association was highlighted in centenarians. Concerning SIRT1, no
association between the SNPs under study and longevity was observed in the only
available report. Current findings suggest that both IGF-1R and FOXO3A
polymorphisms could be associated with longevity. The high degree of between
study heterogeneity and the low number of available studies underline the need
for further methodologically adequate analyses to confirm this evidence.
PMID- 24350934
TI - Role of melatonin in alleviating cold stress in Arabidopsis thaliana.
AB - Melatonin (N-acetyl-5-methoxytryptamine) has been implicated in abiotic and
biotic stress tolerance in plants. However, information on the effects of
melatonin in cold-stress tolerance in vivo is limited. In this study, the effect
of melatonin was investigated in the model plant Arabidopsis thaliana challenged
with a cold stress at 40C for 72 and 120 hr. Melatonin-treated plants (10 and 30
MUm) had significantly higher fresh weight, primary root length, and shoot height
compared with the nontreated plants. To aid in the understanding of the role of
melatonin in alleviating cold stress, we investigated the effects of melatonin
treatment on the expression of cold-related genes. Melatonin up-regulated the
expression of C-repeat-binding factors (CBFs)/Drought Response Element Binding
factors (DREBs), a cold-responsive gene, COR15a, a transcription factor involved
in freezing and drought-stress tolerance CAMTA1 and transcription activators of
reactive oxygen species (ROS)-related antioxidant genes, ZAT10 and ZAT12,
following cold stress. The up-regulation of cold signaling genes by melatonin may
stimulate the biosynthesis of cold-protecting compounds and contribute to the
increased growth of plants treated with exogenous melatonin under cold stress.
PMID- 24350935
TI - [Prospective, multicentric, non-interventional study to assess the existing
treatment of type 2 diabetes mellitus patients inadequately controlled with
metformin monotherapy - KOMETA CZ].
AB - After several years of diabetes, the first line anti-diabetic therapy of
metformin usually starts failing. The KOMETA study was a prospective,
multicentric, non-interventional epidemiological study in patients with type 2
diabetes mellitus inadequately controlled with metformin therapy. The study was
conducted between 2010 and 2011. The study demonstrated a significant improvement
in diabetes control, reduction of waist circumference, reduction in blood
pressure and adjustment of dyslipidemia compared to baseline. Based on this
study, our doctors select anti-diabetic drugs responsibly and they often use
medicines without the hypoglycaemia risk. Nevertheless, more than two thirds of
patients achieve the HbA1c control of under 6% according to IFCC. The main
conclusion of this study is that under standard conditions it is possible to
achieve full metabolic control of type
PMID- 24350936
TI - [Efficacy and safety of vildagliptin as a second-line therapy vs other oral
antidiabetic agents in patients with type 2 diabetes: Czech results within the
worldwide prospective cohort EDGE study].
AB - INTRODUCTION: Metformin monotherapy is recommended as initial treatment of type 2
diabetes. The selection of optimal second-line therapy that is often necessary
due to the progressive nature of the disease is still a subject of ongoing
discussions. AIM OF THE STUDY: The aim of the international EDGE (Effectiveness
of Diabetes control with vildaGliptin and vildagliptin/mEtformin) study was to
prospectively compare the efficacy and safety of vildagliptin vs other oral
antidiabetic agents in patients with type 2 diabetes not adequately controlled on
monotherapy in a real-life clinical setting. In this paper, we present the data
of patients participating in the EDGE study in the Czech Republic. MATERIAL AND
METHODS: Patients with type 2 diabetes not adequately controlled on monotherapy
were enrolled into the study, and randomised into either the vildagliptin arm or
control arm with another OAD at the discretion of the treating physician.
Patients with the addition of other incretin-based medications were not enrolled
into the study. The efficiency was evaluated as a proportion of patients reaching
the combined endpoint of decreasing HbA1c> 3 mmol/mol without hypoglycaemia,
peripheral oedema or treatment termination due to gastrointestinal side effects
during the 12 months of treatment. RESULTS: 654 patients were enrolled into the
study in the Czech Republic. The mean age of the patients when enrolled into the
study (vildagliptin group vs control group) was 59.5 +/- 10.6 vs 63.7 +/- 8.5
years, mean body mass index was 32.4 +/- 5.7 vs 31.7 +/- 6.5 kg/m2, mean HbA1c
was 62 +/- 12 vs 64 +/- 11 mmol/mol. The probability of reaching the combined
primary endpoint (calculated using a binary logistic regression model to
calculate the odds ratios with 95% confidence intervals) was higher for
vildagliptin regardless of baseline HbA1c or type of medication added in the
control group. Primary endpoint was reached by 60.6 % of patients in the
vildagliptin group vs 51.3 % of patients in the control group, odds ratio 1.46
(1.06, 1.99); p< 0.019. The proportion of patients reaching secondary endpoint
(HbA1c< 54 mmol/mol without hypoglycemic event or weight gain 3 % with baseline
glycated hemoglobin > 54 mmol/mol was higher for vildagliptin 45.7 % vs 31.4 % in
the control arm, odds ratio 1.84 (1.26, 2.68), p< 0.001. The rate of adverse
events was comparable in both groups. CONCLUSION: In a real-life clinical set
ting, the percentage of patients reaching the combined endpoint of decreasing
HbA1c> 3 mmol/mol, without hypoglycaemia, peripheral oedema or treatment
termination due to gastrointestinal side effects was higher after the addition of
vildagliptin as compared to other antidiabetic agents with comparable rate of
side effects.
PMID- 24350937
TI - [Indicators of inflammation in patients with coronary atherosclerosis - role of
usCRP in diagnosis and disease progression prediction].
AB - Atherosclerosis is being nowadays defined as chronic subclinical inflammatory
disease. Recently published clinical and laboratory studies have shown that
subclinical inflammation represents main role in initiation of creation, in
progress and destabilization of atherosclerotic plaque. Screening including
traditional cardiovascular risk factors fails in identification in more than 50%
of individuals with later development of acute coronary syndrome. According to
above mentioned reason indicators are being searched for, which would be usable
to monitor the activity of atherosclerotic process. According to role of
subclinical inflammatory process in pathogenesis of atherosclerosis, the
determination of C-reactive protein using ultrasensitive method is being showed
as perspective marker. Ultrasensitive C-reactive protein represents a strong,
independent predictor of future cardiovascular events in apparently heal-thy
individuals and has also prognostic utility in patients with acute coronary
syndromes. Predictive capacity of C-reactive protein determination is independent
of traditional risk factors and offers prognostic advantage as opposed to
determination of lipids alone. The paper provides a review of currently available
knowledge of possibilities for utilization of C-reactive protein laboratory
assessment, as the main representative of acute phase proteins, in monitoring of
creation and severity of coronary atherosclerosis, in possibilities of the
disease prognosis determination and prediction of its acute complications, and
also in prediction of prognosis in patient with already existing acute
complication.
PMID- 24350938
TI - [Contemporary view on liver impairment in heart failure].
AB - Cardiac failure has a negative impact on the function of all parenchymatous
organs, based both on the low organ perfusion in the left-sided forward failure
and on the venous congestion in the right-sided backward failure. Current studies
dealing with the cardiac hepatopathy focus not only on the liver enzyme changes,
but also analyse its clinical and prognostic relevance. The aim of the article is
to provide the comprehensive and contemporary view on liver dysfunction in heart
failure patients.
PMID- 24350939
TI - [The position of tiotropium in new treatment guidelines for chronic obstructive
pulmonary disease].
AB - Chronic obstructive pulmonary disease is a significant syndrome of internal
medicine with serious health, social and economic impacts. Globally, tiotropium
is the longest used and through the randomised studies the most examined
representative of inhalation long-acting antimuscarinics. In routine practice,
this treatment group is identified with a globally known abbreviation LAMA (or U
LAMA, U means ultralong-acting with dosing every 24 hours). Pharmacological
agents of the LAMA (U-LAMA) group are included in a significant number of all
important treatment guidelines. The Czech guidelines place these medicines into
the first line of general medication - for all symptomatic patients, regardless
of the stage, age and comorbidities. The article describes the role of LAMA
(namely tiotropium) in the treatment of chronic obstructive pulmonary disease and
also relevant evidence of the efficacy and safety of both tiotropium dosage forms
(HandHaler and Respimat) in detail.
PMID- 24350941
TI - [Inflammatory borrelia - associated dilated cardiomyopathy].
AB - A case of a 44-year-old female patient is described, examined for several weeks
with shortness of breath and the symptoms of heart decompensation after repeated
untreated respiratory infections. Echocardiographically determined diffuse
hypokinesis of dilated left ventricle with ejection fraction of 20%.
Coronarographic examination without any significant finding at the coronary bed.
MRI of the myocardium supported the suspicion of myocarditis, followed by the
endomyocardial biopsy with electron microscopic evidence of borrelia fragments.
After the causal and symptomatic treatment, the patient experienced significant
clinical improvement and full normalisation of the finding.
PMID- 24350940
TI - [Present and future of pharmaco-arteriothromboprophylaxis in clinical practice.
Guidelines of Angiology Section of Slovak Medical Chamber].
AB - Antiplatelet therapy by acetylsalicylic acid (aspirin) provided pivotal advances
in the prevention and treatment of organovascular (cardiovascular,
cerebrovascular, extremitovascular, renovascular, genitovascular,
mesenteriovascular, bronchopulmovascular, oculovascular, otovascular and other)
arterial ischemic diseases. Currently available antiplatelet drugs have some
limitations which might be overcomed by improved dosing regimens, use of
combination of agents affecting different platelet functions and, in particular,
by the new antiplatelet drugs (new arterial antithrombotics) with distinct
pharmacodynamic properties offering new advantages, including faster onset of
action, greater potency, and reversibility of effects. Document (Guidelines) of
the Angiology Section of the Slovak Medical Chamber (AS SMS, 2013).
PMID- 24350942
TI - [Serious risk related to oral use of sodium phosphate solution].
AB - Sodium phosphate solutions are commonly used to cleanse the bowel in preparation
for colonoscopy, for barium enema or surgical procedures and eventually for
treatment of severe constipation. Though relatively safe, these drugs must be
used with caution in patients with kidney disease, small intestinal disorders, or
poor gut motility and are prohibited in renal insufficiency and bowel
obstruction. Especially elderly patients are at increased risk for phosphate
intoxication due to decreased glomerular filtration rate, concomitant medication
use, and systemic and gastrointestinal diseases. Sodium phosphate solution could
induce by at-risk patients serious electrolyte abnormalities (hyperphosphatemia,
hypocalcemia, hypokalemia) and acute kidney injury called acute phosphate
nephropathy, which is potentially life-threatening condition with slowly
progressive renal insufficiency. This article gives a report on two cases of
severe adverse effects after administration of oral sodium phosphate solution: an
elderly women who developed increase in serum phosphate with compensatory severe
hypokalcemia with tetany; and an elderly man who developed acute phosphate
nephropathy following colon preparation prior to colonoscopy and barium enema.
Especially in elderly and in patients in whom sodium phosphate solution is
contraindicated or should be used with caution, we recommend to use isosmotic
macrogol (polyethylene glycol) solution for the bowel cleansing a for the
treatment of constipation.
PMID- 24350943
TI - [Histiocytic sarcoma].
AB - Histiocytic sarcoma is a neoplasm arising from the histiocytes. Histiocytic
neoplasms are among the rarest malignancies of lymphatic tissues. Occurs in less
than 1% of all malignancies affecting lymph nodes and soft tissues [1,2]. The
exact incidence of histiocytic sarcoma has not been described so far. In this
article, we report three patients with HS, who were treated at the departement of
Internal medicine, haematology and oncology, Faculty Hospital Brno. Despite the
fact that all these patients had the same disease, the treatment effects differ
depending on the stage of the disease at the time of diagnosis.
PMID- 24350944
TI - Prognostic utility of basaloid differentiation in oropharyngeal cancer.
AB - BACKGROUND: Human papillomavirus (HPV) is recognized as the key risk factor for a
distinct subset of oropharyngeal squamous cell carcinoma. P16 is a reliable,
sensitive surrogate marker for HPV and confers a positive prognostic advantage.
Basaloid differentiation on hematoxylin and eosin (H&E) staining is anecdotally
noted by some pathologists to be associated with p16 positivity. This
association, however, has not been adequately quantified in the literature, nor
has the prognostic implications of basaloid differentiation been described.
OBJECTIVES: 1) To correlate the H&E staining feature of basaloid differentiation
with p16 positivity in oropharyngeal cancer. 2) To investigate the prognostic
utility of basaloid differentiation in oropharyngeal cancer survival. METHODS:
Retrospective cross-sectional study of all patients diagnosed with and treated
for oropharyngeal cancer at a single tertiary cancer center from 2002 to 2009.
Tissue microarrays (TMAs) were generated from 208 oropharyngeal tumor specimens
stained with H&E and immunohistochemical markers. These oropharyngeal TMAs were
utilized in several previous publications. Samples were scored for basaloid
differentiation by a pathologist blinded to the p16 result. A multivariate
survival analysis with Cox-regression and Kaplan-Meier survival analysis was
performed. RESULTS: In the 208 samples, basaloid differentiation correlated with
p16 positivity (Spearman's rho 0.435). Basaloid differentiation and p16
positivity were both independent predictors of improved survival. The 5 year
disease specific survival (DSS) was 73% for p16 positive tumors and 35% for p16
negative tumors (p < 0.001). Similarly, the 5 year DSS of basaloid differentiated
tumors was 74% compared to 41% for non-basaloid tumors (p = 0.001). Patients with
p16 positive and basaloid differentiated tumors had the best survival outcomes
with a 5 year DSS of 80%. CONCLUSIONS: Basaloid differentiation is a feature on
H&E which correlates with p16 positivity and is a simple, inexpensive,
independent, positive prognostic indicator of comparable magnitude to p16 status.
Due to the added prognostic value of basaloid differentiation, this feature
should be routinely reported by qualified pathologists.
PMID- 24350945
TI - The learning style preferences of chiropractic students: A cross-sectional study.
AB - Objective : The aims of our study were to measure the learning style preferences
of chiropractic students and to assess whether they differ across the 5 years of
chiropractic study. Methods : A total of 407 (41.4% females) full-degree,
undergraduate, and postgraduate students enrolled in an Australian chiropractic
program agreed to participate in a cross-sectional survey comprised of basic
demographic information and the Visual, Aural, Read/Write, Kinesthetic (VARK)
questionnaire, which identifies learning preferences on four different subscales:
visual, aural, reading/writing, and kinesthetic. Multivariate analysis of
variance and the chi(2) test were used to check for differences in continuous
(VARK scores) and categorical (VARK category preference) outcome variables.
Results : The majority of chiropractic students (56.0%) were found to be
multimodal learners. Compared to the other learning styles preferences,
kinesthetic learning was preferred by a significantly greater proportion of
students (65.4%, p < .001) and received a significantly greater mean VARK score
(5.66 +/- 2.47, p < .001). Conclusions : To the best of our knowledge, this is
the first time chiropractic students have been shown to be largely multimodal
learners with a preference for kinesthetic learning. While this knowledge may be
beneficial in the structuring of future curricula, more thorough research must be
conducted to show any beneficial relationship between learning style preferences
and teaching methods.
PMID- 24350946
TI - Test anxiety and academic performance in chiropractic students.
AB - Objective : We assessed the level of students' test anxiety, and the relationship
between test anxiety and academic performance. Methods : We recruited 166 third
quarter students. The Test Anxiety Inventory (TAI) was administered to all
participants. Total scores from written examinations and objective structured
clinical examinations (OSCEs) were used as response variables. Results : Multiple
regression analysis shows that there was a modest, but statistically significant
negative correlation between TAI scores and written exam scores, but not OSCE
scores. Worry and emotionality were the best predictive models for written exam
scores. Mean total anxiety and emotionality scores for females were significantly
higher than those for males, but not worry scores. Conclusion : Moderate-to-high
test anxiety was observed in 85% of the chiropractic students examined. However,
total test anxiety, as measured by the TAI score, was a very weak predictive
model for written exam performance. Multiple regression analysis demonstrated
that replacing total anxiety (TAI) with worry and emotionality (TAI subscales)
produces a much more effective predictive model of written exam performance. Sex,
age, highest current academic degree, and ethnicity contributed little additional
predictive power in either regression model. Moreover, TAI scores were not found
to be statistically significant predictors of physical exam skill performance, as
measured by OSCEs.
PMID- 24350949
TI - Housing as health care--New York's boundary-crossing experiment.
PMID- 24350948
TI - Metabolism and development - integration of micro computed tomography data and
metabolite profiling reveals metabolic reprogramming from floral initiation to
silique development.
AB - The interrelationship of morphogenesis and metabolism is a poorly studied
phenomenon. The main paradigm is that development is controlled by gene
expression. The aim of the present study was to correlate metabolism to early and
late stages of flower and fruit development in order to provide the basis for the
identification of metabolic adjustment and limitations. A highly detailed picture
of morphogenesis is achieved using nondestructive micro computed tomography. This
technique was used to quantify morphometric parameters of early and late flower
development in an Arabidopsis thaliana mutant with synchronized flower
initiation. The synchronized flower phenotype made it possible to sample enough
early floral tissue otherwise not accessible for metabolomic analysis. The
integration of metabolomic and morphometric data enabled the correlation of
metabolic signatures with the process of flower morphogenesis. These signatures
changed significantly during development, indicating a pronounced metabolic
reprogramming in the tissue. Distinct sets of metabolites involved in these
processes were identified and were linked to the findings of previous gene
expression studies of flower development. High correlations with basic leucine
zipper (bZIP) transcription factors and nitrogen metabolism genes involved in the
control of metabolic carbon : nitrogen partitioning were revealed. Based on these
observations a model for metabolic adjustment during flower development is
proposed.
PMID- 24350947
TI - The Alzheimer pandemic: is paracetamol to blame?
AB - HISTORICAL BACKGROUND: The clinical recognition of a form of dementia closely
resembling Alzheimer's disease dates from around 1800. The role of analgesics
derived from coal-tar in the spread of the pandemic is traced in terms of the
introduction of phenacetin (PN) in 1887; its nephrotoxicity; the observation of
lesions characteristic of the disease by Fischer and Alzheimer; the discovery of
paracetamol (PA) as the major metabolite of PN; the linking of kidney injury and
dementia with high PN usage; and the failure of PN replacement by PA to halt and
reverse the exponential, inexorable rise in the incidence of Alzheimer-type
dementia. Fischer observed his first case before Alzheimer; it is proposed to
rename the syndrome Fischer-Alzheimer disease (F-AD). Disease development: PA
metabolising enzymes are localised in the synaptic areas of the frontal cortex
and hippocampus, where F-AD lesions arise. The initiating chemical lesions in
liver poisoning comprise covalent binding of a highly reactive product of PA
metabolism to proteins; similar events are believed to occur in brain, where
alterations in the antigenic profiles of cerebral proteins activate the
microglia. beta-Amyloid forms, and, like PA itself, induces nitric oxide
synthase. Peroxynitrite modifies cerebral proteins by nitrating tyrosine
residues, further challenging the microglia and exacerbating the amyloid cascade.
Spontaneous reinnervation, N-acetyl cysteine administration and tyrosine
supplementation may attenuate the early stages of F-AD development. CONCLUSION: F
AD is primarily a man-made condition with PA as its principal risk factor.
PMID- 24350950
TI - Use of selective serotonin reuptake inhibitors during pregnancy and risk of
autism.
AB - BACKGROUND: Studies have raised concern about an association between the use of
selective serotonin reuptake inhibitors (SSRIs) during pregnancy and an increased
risk of autism spectrum disorders in the offspring. METHODS: We conducted a
cohort study of all singleton live births in Denmark from 1996 through 2005
(626,875 births), with follow-up through 2009. Using Danish population
registries, we linked information on maternal use of SSRIs before and during
pregnancy, autism spectrum disorders diagnosed in the offspring, and a range of
potential confounders. We used a survival analysis of the time to diagnosis in
the offspring with Poisson regression to estimate rate ratios of autism spectrum
disorders according to maternal use of SSRIs. RESULTS: During 5,057,282 person
years of follow-up, we identified 3892 cases of autism spectrum disorder
(incidence rate, 77.0 per 100,000 person-years). A total of 52 cases during
42,400 person-years of follow-up involved offspring of women who were exposed to
SSRIs during their pregnancy (incidence rate, 122.6 per 100,000 person-years). As
compared with no use of SSRIs both before and during pregnancy, use during
pregnancy was not associated with a significantly increased risk of autism
spectrum disorders (fully adjusted rate ratio, 1.20; 95% confidence interval
[CI], 0.90 to 1.61). Among women who received SSRIs before pregnancy but not
during pregnancy, the corresponding fully adjusted rate ratio was 1.46 (95% CI,
1.17 to 1.81). CONCLUSIONS: We did not detect a significant association between
maternal use of SSRIs during pregnancy and autism spectrum disorder in the
offspring. On the basis of the upper boundary of the confidence interval, our
study could not rule out a relative risk up to 1.61, and therefore the
association warrants further study. (Funded by the Danish Health and Medicines
Authority.).
PMID- 24350951
TI - Shattuck Lecture. Chronic infectious disease and the future of health care
delivery.
PMID- 24350952
TI - Images in clinical medicine. Lingual squamous-cell carcinoma.
PMID- 24350953
TI - Case records of the Massachusetts General Hospital. Case 39-2013. A 57-year-old
woman with painful bullous skin lesions.
PMID- 24350954
TI - Gonadal steroids and body composition, strength, and sexual function in men.
PMID- 24350955
TI - Gonadal steroids and body composition, strength, and sexual function in men.
PMID- 24350956
TI - Gonadal steroids and body composition, strength, and sexual function in men.
PMID- 24350957
TI - Gonadal steroids and body composition, strength, and sexual function in men.
PMID- 24350958
TI - Gonadal steroids and body composition, strength, and sexual function in men.
PMID- 24350959
TI - Cystatin C versus creatinine for kidney function-based risk.
PMID- 24350960
TI - Cystatin C versus creatinine for kidney function-based risk.
PMID- 24350961
TI - Cystatin C versus creatinine for kidney function-based risk.
PMID- 24350962
TI - Cystatin C versus creatinine for kidney function-based risk.
PMID- 24350963
TI - Surgical-readmission rates and quality of care.
PMID- 24350964
TI - Surgical-readmission rates and quality of care.
PMID- 24350965
TI - Surgical-readmission rates and quality of care.
PMID- 24350966
TI - Resuscitation fluids.
PMID- 24350967
TI - Resuscitation fluids.
PMID- 24350968
TI - Resuscitation fluids.
PMID- 24350969
TI - Resuscitation fluids.
PMID- 24350970
TI - Resuscitation fluids.
PMID- 24350971
TI - Survey of oncologists about shortages of cancer drugs.
PMID- 24350972
TI - Videos in clinical medicine. Pulmonary-artery catheterization.
PMID- 24350973
TI - Images in clinical medicine. Beans and beaks.
PMID- 24350975
TI - Adverse events appear to unblind clinical trials in irritable bowel syndrome.
AB - BACKGROUND: Clinical trial design is challenging in irritable bowel syndrome
(IBS) due in part to a high placebo effect. We postulated that the mere presence
of an adverse event (AE) may unmask patients in clinical trials who are assigned
to the active agent, and this may lead to higher reported efficacy. METHODS: We
evaluated therapies receiving at least a Grade 1B from the American College of
Gastroenterology Task Force for IBS or which passed recent phase III clinical
trials. Therapies with AE data derived from less than 50 patients in each study
arm were excluded. Statistically significant excess AE were identified, risk
difference was calculated for each AE, and incidence of AE in the treatment arm
was reported. We examined the relationship of attributable drug benefit, defined
as the reciprocal of number-needed-to-treat found in literature, with various
measures of AE incidence. KEY RESULTS: Attributable drug benefit correlated
significantly with average AE risk difference, calculated as treatment arm AE
incidence minus placebo arm AE incidence (R(2) = 0.70, p = 0.039), and also with
highest treatment arm AE incidence (R(2) = 0.70, p = 0.038) for each therapy.
There were also trends toward correlation with average treatment arm AE incidence
(R(2) = 0.54, p = 0.096) and highest AE risk difference (R(2) = 0.63, p = 0.059)
for each therapy. CONCLUSIONS & INFERENCES: Our study suggests that higher AE
incidence on active therapy is associated with more beneficial patient-reported
outcomes in IBS clinical trials. This raises the issue of spontaneous unblinding.
PMID- 24350974
TI - Disentangling the interaction among host resources, the immune system and
pathogens.
AB - The interaction between the immune system and pathogens is often characterised as
a predator-prey interaction. This characterisation ignores the fact that both
require host resources to reproduce. Here, we propose novel theory that considers
how these resource requirements can modify the interaction between the immune
system and pathogens. We derive a series of models to describe the energetic
interaction between the immune system and pathogens, from fully independent
resources to direct competition for the same resource. We show that increasing
within-host resource supply has qualitatively distinct effects under these
different scenarios. In particular, we show the conditions for which pathogen
load is expected to increase, decrease or even peak at intermediate resource
supply. We survey the empirical literature and find evidence for all three
patterns. These patterns are not explained by previous theory, suggesting that
competition for host resources can have a strong influence on the outcome of
disease.
PMID- 24350978
TI - Transparent and stretchable high-performance supercapacitors based on wrinkled
graphene electrodes.
AB - Transparent and/or stretchable energy storage devices have attracted intense
attention due to their unique optical and/or mechanical properties as well as
their intrinsic energy storage function. However, it remains a great challenge to
integrate transparent and stretchable properties into an energy storage device
because the currently developed electrodes are either transparent or stretchable,
but not both. Herein, we report a simple method to fabricate wrinkled graphene
with high stretchability and transparency. The resultant wrinkled graphene sheets
were used as both current collector and electrode materials to develop
transparent and stretchable supercapacitors, which showed a high transparency
(57% at 550 nm) and can be stretched up to 40% strain without obvious performance
change over hundreds of stretching cycles.
PMID- 24350979
TI - A new species of Burkholderia isolated from sugarcane roots promotes plant
growth.
AB - Sugarcane is a globally important food, biofuel and biomaterials crop. High
nitrogen (N) fertilizer rates aimed at increasing yield often result in
environmental damage because of excess and inefficient application. Inoculation
with diazotrophic bacteria is an attractive option for reducing N fertilizer
needs. However, the efficacy of bacterial inoculants is variable, and their
effective formulation remains a knowledge frontier. Here, we take a new approach
to investigating diazotrophic bacteria associated with roots using culture
independent microbial community profiling of a commercial sugarcane variety
(Q208(A) ) in a field setting. We first identified bacteria that were markedly
enriched in the rhizosphere to guide isolation and then tested putative
diazotrophs for the ability to colonize axenic sugarcane plantlets (Q208(A) ) and
promote growth in suboptimal N supply. One isolate readily colonized roots, fixed
N2 and stimulated growth of plantlets, and was classified as a new species,
Burkholderia australis sp. nov. Draft genome sequencing of the isolate confirmed
the presence of nitrogen fixation. We propose that culture-independent
identification and isolation of bacteria that are enriched in rhizosphere and
roots, followed by systematic testing and confirming their growth-promoting
capacity, is a necessary step towards designing effective microbial inoculants.
PMID- 24350980
TI - Reconstituted biosynthesis of the nonribosomal macrolactone antibiotic
valinomycin in Escherichia coli.
AB - The structural complexity of nonribosomal peptides (NRPs) impeding economic
chemical synthesis and poor cultivability of source organisms limits the
development of bioprocesses for novel bioactive compounds. Since nonribosomal
peptide synthetases (NRPSs) assemble NRPs from simple amino acid building blocks,
heterologous expression of NRPSs in a robust and easy to manipulate expression
host is an attractive strategy to make pharmaceutically relevant NRPs more
accessible and is also a basis for engineering of these enzymes to generate novel
synthetic bioactive compounds. Here we show a systematic approach for the
heterologous expression of the 654 kDa heterodimeric valinomycin synthetase
(VlmSyn) from Streptomyces tsusimaensis in a soluble and active form in
Escherichia coli. VlmSyn activity and precursor requirements were determined in
vitro and provided evidence for a previously proposed model of valinomycin
biosynthesis. In vivo production of recombinant valinomycin, a macrolactone
antibiotic with reported antifungal, antibacterial, and antiviral activities, was
achieved using an engineered E. coli strain growing in inexpensive media and
independent of the supplementation with precursors and further optimization of
the cultivation conditions. Tailoring of VlmSyn in E. coli paves the way to the
production of novel valinomycin analogues in the future.
PMID- 24350982
TI - Testing sex ratio theory with the malaria parasite Plasmodium mexicanum in
natural and experimental infections.
AB - The malaria parasite (Plasmodium) life history accords well with the assumptions
of local mate competition (LMC) of sex ratio theory. Within a single meal of the
blood-feeding vector, sexually dimorphic gametocyte cells produce gametes
(females produce one, males several) that mate and undergo sexual recombination.
The theory posits several factors drive the Plasmodium sex ratio: male fecundity
(gametes/male gametocyte), number and relative abundance of parasite clones, and
gametocyte density. We measured these traits for the lizard malaria parasite,
Plasmodium mexicanum, with a large sample of natural infections and infections
from experiments that manipulated clonal diversity. Sex ratio in single-clone
infections was slightly female-biased, but matched predictions of theory for this
low-fecundity species. Sex ratio was less female-biased in clonally diverse
infections as predicted by LMC for the experimental, but not natural infections.
Gametocyte density was not positively related to sex ratio. These results are
explained by the P. mexicanum life history of naturally low clonal diversity and
high gametocyte production. This is the first study of a natural malaria system
that examines all traits relevant to LMC in individual vertebrate hosts and
suggests a striking example of sex ratio theory having significance for human
public health.
PMID- 24350983
TI - Dammarane-type saponins from Ziziphus jujube.
AB - Two new dammarane-type saponins jujubosides D and E, together with three known
compounds, were isolated from the seeds of Ziziphus jujube. Their structures were
elucidated on the basis of chemical and spectroscopic evidence. Compounds 1-5
showed lipoxygenase-inhibiting activity.
PMID- 24350981
TI - Ambient temperature enhanced freezing tolerance of Chrysanthemum dichrum CdICE1
Arabidopsis via miR398.
AB - BACKGROUND: ICE (Inducer of CBF Expression) family genes play an important role
in the regulation of cold tolerance pathways. In an earlier study, we isolated
the gene CdICE1 from Chrysanthemum dichrum and demonstrated that freezing
tolerance was enhanced by CdICE1 overexpression. Therefore, we sought to
determine the mechanism by which ICE1 family genes participate in freezing
tolerance. RESULTS: Using EMSA (Electrophoretic Mobility Shift Assay) and yeast
one-hybrid assays, we confirmed that CdICE1 binds specifically to the MYC element
in the CdDREBa promoter and activates transcription. In addition, overexpression
of CdICE1 enhanced Arabidopsis freezing tolerance after transition from 23
degrees C to 4 degrees C or 16 degrees C. We found that after acclimation to 4
degrees C, CdICE1, like Arabidopsis AtICE1, promoted expression of CBFs (CRT/DRE
Binding Factor) and their genes downstream involved in freezing tolerance,
including COR15a (Cold-Regulated 15a), COR6.6, and RD29a (Responsive to
Dessication 29a). Interestingly, we observed that CdICE1-overexpressing plants
experienced significant reduction in miR398. In addition, its target genes CSD1
(Copper/zinc Superoxide Dismutase 1) and CSD2 showed inducible expression under
acclimation at 16 degrees C, indicating that the miR398-CSD pathway was involved
in the induction of freezing tolerance. CONCLUSIONS: Our data indicate that
CdICE1-mediated freezing tolerance occurs via different pathways, involving
either CBF or miR398, under acclimation at two different temperatures.
PMID- 24350984
TI - The tumor necrosis factor receptor-associated factor (TRAF)-like family protein
SEVEN IN ABSENTIA 2 (SINA2) promotes drought tolerance in an ABA-dependent manner
in Arabidopsis.
AB - Tumor necrosis factor receptor-associated factor (TRAF) proteins play crucial
roles in plant development and response to abiotic stress. Here, we present
genetic evidence that SEVEN IN ABSENTIA 2 (SINA2), a TRAF-like family protein, is
involved in abscisic acid (ABA)-related drought stress signaling in Arabidopsis.
Gene expression, protein subcellular localization, protein-protein interaction,
and a transient transcription dual-luciferase assay were performed. The drought
tolerance of SINA2 loss-of-function mutants and SINA2-overexpressing plants was
investigated. In Arabidopsis, SINA2 was significantly induced by ABA and drought
treatment. The SINA2-YFP fusion protein was predominately localized in the nuclei
and cytoplasm. Loss of function of SINA2 (sina2) reduced drought tolerance,
whereas overexpression of SINA2 increased stomatal closure, decreased water loss,
and therefore improved drought resistance in transgenic plants. Upon ABA
treatment, expression of some key ABA- and stress-responsive genes decreased in
the sina2 mutant, but increased in SINA2-overexpressing plants. Furthermore,
SINA2 was induced in the ABA-deficient mutant by ABA, but not by drought stress.
Thus, the drought response of SINA2 was ABA-dependent. ProSINA2::LUC expression
in Arabidopsis protoplasts further revealed that ABA-responsive element (ABRE)
binding (AREB) protein 1 (AREB1) AREB2 and ABRE-binding factor 3 (ABF3) might
regulate SINA2 expression at the transcriptional level. Our results indicate that
SINA2 functions as a positive molecular link between drought tolerance and ABA
signaling in Arabidopsis.
PMID- 24350985
TI - Association between allergic rhinitis and asthma in a Northern Alberta cohort.
AB - BACKGROUND: Many published epidemiologic studies confirm a marked increase in the
prevalence of asthma and allergic rhinitis. The link between allergic rhinitis
and asthma has been extensively studied and approximately 75% of patients with
asthma have allergic rhinitis. The proportion of patients with asthma in
populations of allergic rhinitis patients has not been well studied. OBJECTIVE:
The purpose of this study is to estimate the prevalence of undiagnosed asthma in
a specific population of patients presenting to an Otolaryngologist with symptoms
of allergic rhinitis. STUDY DESIGN: Prospective cohort study. METHODS: Patients
presenting with symptoms of allergic rhinitis to two tertiary care Rhinology
practices in Northern Alberta were asked to undergo allergy skin testing, serum
IgE quantification, and pulmonary functional testing. Patients with previous
asthma screening or known history of reactive airway disease or asthma were
excluded. RESULTS: 107 patients with allergic rhinitis symptoms were recruited
between September 2010 to January 2013. Patients predominantly had perennial or
persistent rhinitis (64.5%) with moderate-severe symptoms (50.5%). While only
14.9% of patients had abnormal IgE levels, 68.8% had positive skin testing.
Abnormal pulmonary function tests were obtained in 39.1% of patients and 26.1% of
patients were diagnosed with asthma. CONCLUSIONS: There is a high prevalence of
undiagnosed asthma in patients presenting to tertiary Rhinology care with
moderate to severe allergic rhinitis symptoms. Screening lung function testing
should be considered in this patient population.
PMID- 24350986
TI - The effect of 2% chlorhexidine and cleansing wipes on capillary blood glucose
sampling accuracy of a fingertip soiled with apple: a case crossover study
design.
PMID- 24350988
TI - Concentration-dependent Sildenafil citrate (Viagra) effects on ROS production,
energy status, and human sperm function.
AB - Literature regarding the effects of sildenafil citrate on sperm function remains
controversial. In the present study, we specifically wanted to determine if
mitochondrial dysfunction, namely membrane potential, reactive oxygen species
production, and changes in energy content, are involved in in vitro sildenafil
induced alterations of human sperm function. Sperm samples of healthy men were
incubated in the presence of 0.03, 0.3, and 3 MUM sildenafil citrate in a
phosphate buffered saline (PBS)-based medium for 2, 3, 12, and 24 hours. Sperm
motility and viability were evaluated and mitochondrial function, i.e.,
mitochondrial membrane potential and mitochondrial superoxide production were
assessed using flow-cytometry. Additionally, adenosine triphosphate (ATP) levels
were determined by high performance liquid chromatography (HPLC) analysis.
Results show a decrease in sperm motility correlated with the level of
mitochondria-generated superoxide, without a visible effect on mitochondrial
membrane potential or viability upon exposure to sildenafil. The effect on both
motility and superoxide production was higher for the intermediate concentration
of sildenafil (0.3 uM) indicating that the in vitro effects of sildenafil on
human sperm do not vary linearly with drug concentration. Adenosine triphosphate
levels also decreased following sildenafil exposure, but this decrease was only
detected after a decrease in motility was already evident. These results suggest
that along with the level of ATP and mitochondrial function other factors are
involved in the early sildenafil-mediated decline in sperm motility. However, the
further decrease in ATP levels and increase in mitochondria-generated reactive
oxygen species after 24 hours of exposure might further contribute towards
declining sperm motility.
PMID- 24350987
TI - Future agents and treatment directions in multiple myeloma.
AB - The development of bortezomib and immunomodulatory agents resulted in a
revolution in the treatment of multiple myeloma (MM). Moreover, second-generation
proteasome inhibitors (carfilzomib) and immunomodulatory agents (pomalidomide)
have recently been approved. Nevertheless, the incurability of this disease
requires other drugs with different mechanisms of action to either prolong the
survival of patients refractory to current therapies, or achieve cure. Active
research has been done exploring the pathogenesis of MM and searching for novel,
druggable targets. In this regard, some of these novel agents seem promising,
such as monoclonal antibodies (anti-CD38 - daratumumab or anti-CS1 - elotuzumab)
or the kinesin protein inhibitor Arry-520. Other agents under investigation are
kinase inhibitors, signaling pathways inhibitors or deacetylase inhibitors. With
so many novel agents under investigation, future therapy in MM will probably
involve the combined use of the already approved drugs with some of those newly
discovered.
PMID- 24350991
TI - Detection of circulating tumor cells during follow-up of patients with early
breast cancer: Clinical utility for monitoring of therapy efficacy.
AB - INTRODUCTION: Circulating tumor cells (CTCs) detection prior to and during
therapy is considered as an independent and strong prognostic marker. The present
study was designed to isolate and characterize CTCs in peripheral blood of an
early breast cancer (BC) patient as a biomarker for monitoring treatments
efficacy. MATERIALS AND METHODS: In total, 54 early breast cancer patients
undergoing neoadjuvant and/or adjuvant chemotherapy regimens were enrolled into a
prospective study. CTC detection in blood was performed by AdnaTest
BreastCancer(TM) (AdnaGen AG, Germany), which is based on the detection of EpCAM,
HER2 and MUC1 specific transcripts in enriched CTC-lysates. Additionally, cDNA
from isolated CTCs and PBMC was used for qPCR gene expression analysis of TOP1,
TOP2A, CTSD, ST6, CK19 and reference gene actin. RESULTS: We found that CTCs can
be detected in the peripheral blood of approximately 31% of early stage breast
cancer patients. The presence of CTCs was detected in 36% ER positive, 32% PR
positive and 30% HER2 positive patients. We found no correlation between CTCs and
tumor size, tumor grade, histological grade and receptor status. Only 7% of all
patients remained CTCs positive after adjuvant therapy. Gene expression analysis
revealed a particular heterogeneity of the studied genes. CONCLUSIONS: In
conclusion, CTC detection may be a promising early marker of disease progression
potentially enhancing the difficult therapeutic decisions. Further studies
should, however, clearly demonstrate its utility for both the prediction of
outcome and monitoring the effect of treatment.
PMID- 24350989
TI - Cardiac biomarkers in hyperthyroid cats.
AB - BACKGROUND: Hyperthyroidism has substantial effects on the circulatory system.
The cardiac biomarkers NT-proBNP and troponin I (cTNI) have proven useful in
identifying cats with myocardial disease but have not been extensively
investigated in hyperthyroidism. HYPOTHESIS: Plasma NT-proBNP and cTNI
concentrations are higher in cats with primary myocardial disease than in cats
with hyperthyroidism and higher in cats with hyperthyroidism than in healthy
control cats. ANIMALS: Twenty-three hyperthyroid cats, 17 cats with subclinical
hypertrophic cardiomyopathy (HCM), and 19 euthyroid, normotensive healthy cats
>=8 years of age. Fourteen of the hyperthyroid cats were re-evaluated 3 months
after administration of radioiodine ((131)I). METHODS: Complete history, physical
examination, complete blood count, serum biochemistries, urinalysis, blood
pressure measurement, serum T4 concentration, plasma concentrations of NT-proBNP
and cTNI, and echocardiogram were obtained prospectively from each cat. RESULTS:
Hyperthyroid cats and cats with HCM had plasma NT-proBNP and cTNI concentrations
that were significantly higher than those of healthy cats, but there was no
significant difference between hyperthyroid cats and cats with HCM with respect
to the concentration of either biomarker. In hyperthyroid cats that were re
evaluated 3 months after (131) I treatment, plasma NT-proBNP and cTNI
concentrations as well as ventricular wall thickness had decreased significantly.
CONCLUSIONS AND CLINICAL IMPORTANCE: Although there may be a role for NT-proBNP
in monitoring the cardiac response to treatment of hyperthyroidism, neither NT
proBNP nor cTNI distinguish hypertrophy associated with hyperthyroidism from
primary HCM. Therefore, the thyroid status of older cats should be ascertained
before interpreting NT-proBNP and cTNI concentrations.
PMID- 24350990
TI - Factors associated with Khat use among youths visiting HIV testing and counseling
centers in Gamo Gofa, Southern Ethiopia.
AB - BACKGROUND: The use of khat among youths can be harmful leading to decreased
academic performance, increased risk of contracting HIV and other sexually
transmitted diseases or other psychiatric symptoms. It is believed to be one of
the factors associated with unprotected risky sexual behavior predisposing the
youth for HIV infection and transmission. METHODS: A cross-sectional study was
conducted in South West Ethiopia. A total of 410 participants were recruited in
the study using stratified sampling technique. Data were collected by using
interviewer administered structured questionnaire. Multiple logistic regression
and Cox regression were used to assess the association of independent variables
with the outcome variable. RESULT: Khat use was positively associated with male
gender (OR 2.9; C.I. 1.4 to 6.0), alcohol use (OR 4.8; C.I. 2.1 to 10.6), no
education level (OR 2.6; C.I. 1.1 to 6.2) and not having communication with
parents about khat chewing (OR 2.6; C.I. 1.1 to 6.2). CONCLUSION: Strategies
should be designed to increase awareness of factors associated with khat use
among youths and their parents in order to reduce the prevalence of khat use and
its adverse social and health consequences.
PMID- 24350992
TI - Sequestration of the abrin A chain to the nucleus by BASP1 increases the
resistance of cells to abrin toxicity.
AB - Abrin, a type II ribosome-inactivating protein, comprises A and B subunits
wherein the A subunit harbours toxin activity and the B subunit has a galactose
specific lectin activity. The entry of the protein inside the cell is through the
binding of the B chain to cell surface glycoproteins followed by receptor
mediated endocytosis and retrograde transport. A previous study from our
laboratory showed that different cell lines exhibited differences of as great as
~200-fold in abrin toxicity, prompting the present study to compare the
trafficking of the toxin within cells. Observations made in this regard revealed
that the abrin A chain, after being released into the cytosol, is sequestered
into the nucleus through interaction with a cellular protein of ~25 kDa, BASP1
(brain acid-soluble protein 1). The nuclear localization of the A chain is seen
predominantly in cells that are less sensitive to abrin toxicity and dependent on
the levels of BASP1 in cells. The sequestration by BASP1 renders cells
increasingly resistant to the inhibition of protein synthesis by abrin and the
nucleus act as a sink to overcome cellular stress induced by the toxin.
PMID- 24350993
TI - The effect of poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) (PHBHHx) and human
mesenchymal stem cell (hMSC) on axonal regeneration in experimental sciatic nerve
damage.
AB - This study is designed to evaluate the treatment effect of poly(3-hydroxybutyrate
co-3-hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cells (hMSC) on axonal
regeneration in experimental rat sciatic nerve damage, and compare the results of
this modality with autologous nerve grafting. In Spraque-Dawley albino rats, 10
mm-long experimental nerve gaps were created. Three groups were constituted, the
gap was repaired with autologous nerve graft (autograft group), PHBHHx nerve
graft alone (PHBHHx alone group), and PHBHHx nerve graft with hMSCs inside
(PHBHHx with hMSC group), respectively. The results were evaluated with
functional recovery, electrophysiological evaluation, and histological evaluation
either with light microscopy and transmission electron microscopy for axonal
regeneration and myelin formation. In functional evaluation, autograft and PHBHHx
with hMSC groups showed functional improvement with time, whereas PHBHHx alone
group did not. Electrophysiological evaluation showed better results in autograft
and PHBHHx with hMSC groups when compared to PHBHHx alone group. There was no
statistical difference between autograft and PHBHHx with hMSC groups.
Histological evaluation showed regenerated axons in each group. Autograft group
was better than the others, and PHBHHx with hMSC group was better than PHBHHx
alone group both for axonal regeneration and myelin formation. This study showed
that the nerve grafts which were prepared from PHBHHx with oriented nanofiber
three-dimensional surfaces aided to nerve regeneration, either used alone or with
hMSC. PHBHHx provided better nerve regeneration when used with hMSCs inside than
alone, and reached the same statistical treatment effect in functional evaluation
and electrophysiological evaluation when compared to autografting.
PMID- 24350994
TI - Intracranial injection of PEG-PEI/ROCK II-siRNA improves cognitive impairment in
a mouse model of Alzheimer's disease.
AB - PURPOSE: A plenty of studies have demonstrated that the Rho/ROCK pathway is
involved in the neuronal loss and inhibition of axonal regeneration observed in
Alzheimer's disease (AD). Therefore, we conducted this study to evaluate whether
intracranial injection of PEG-PEI/ROCK II siRNA (PPRS) would improve the
cognitive impairments in a senescence-accelerated mouse (SAM) model of AD.
MATERIALS AND METHODS: Five male senescence-resistant inbred strain (SAMR1) mice
and 15 male senescence-accelerated mouse prone-8 (SAMP8) strain mice were divided
into the following three groups:PPRS group, PEG-PEI/ ROCK II-Scramble (PPRScr)
siRNA group, and normal group (SAMR1). Total volumes of 2.3 MUl of nanoparticles
or saline were intracranially injected under the guidance of a stereotaxic
apparatus. The injections were performed every three days and lasted for two
weeks. Four weeks after injection, the Morris water maze (MWM) was used to
evaluate the spatial learning and memory functions of the mice. Choline
acetyltransferase (ChAT) activity was detected by immunohistochemistry. RESULTS:
Mice in the PPRS-treated group exhibited decreases in escape latencies over the
three successive days of navigating the test and crossing the target quadrant
during the spatial probe test more frequently than did the mice in the PPRScr
treated group. Analyses of ChAT activity revealed that greater numbers of ChAT
positive cells were present in the hippocampal regions of the PPRS-treated mice
than in the PPRScr group. CONCLUSIONS: Intracranial injection of PPRS improved
the cognitive impairments of SAM mice, and this improvement may have been
mediated by enhancement of ChAT activity in the hippocampus.
PMID- 24350995
TI - Design, synthesis, and structure-activity relationship studies of a potent PACE4
inhibitor.
AB - PACE4 plays an important role in the progression of prostate cancer and is an
attractive target for the development of novel inhibitor-based tumor therapies.
We previously reported the design and synthesis of a novel, potent, and
relatively selective PACE4 inhibitor known as a Multi-Leu (ML) peptide. In the
present work, we examined the ML peptide through detailed structure-activity
relationship studies. A variety of ML-peptide analogues modified at the P8-P5
positions with leucine isomers (Nle, DLeu, and DNle) or substituted at the P1
position with arginine mimetics were tested for their inhibitory activity,
specificity, stability, and antiproliferative effect. By incorporating d isomers
at the P8 position or a decarboxylated arginine mimetic, we obtained analogues
with an improved stability profile and excellent antiproliferative properties.
The DLeu or DNle residue also has improved specificity toward PACE4, whereas
specificity was reduced for a peptide modified with the arginine mimetic, such as
4-amidinobenzylamide.
PMID- 24350996
TI - Complementary p- and n-type polymer doping for ambient stable graphene inverter.
AB - Graphene offers great promise to complement the inherent limitations of silicon
electronics. To date, considerable research efforts have been devoted to
complementary p- and n-type doping of graphene as a fundamental requirement for
graphene-based electronics. Unfortunately, previous efforts suffer from undesired
defect formation, poor controllability of doping level, and subtle environmental
sensitivity. Here we present that graphene can be complementary p- and n-doped by
simple polymer coating with different dipolar characteristics. Significantly,
spontaneous vertical ordering of dipolar pyridine side groups of poly(4
vinylpyridine) at graphene surface can stabilize n-type doping at room
temperature ambient condition. The dipole field also enhances and balances the
charge mobility by screening the impurity charge effect from the bottom
substrate. We successfully demonstrate ambient stable inverters by integrating p-
and n-type graphene transistors, which demonstrated clear voltage inversion with
a gain of 0.17 at a 3.3 V input voltage. This straightforward polymer doping
offers diverse opportunities for graphene-based electronics, including logic
circuits, particularly in mechanically flexible form.
PMID- 24350997
TI - An incidence model of the cost of advanced prostate cancer in Spain.
AB - BACKGROUND: Prostate cancer (PCa) is the second leading cancer diagnosed among
men. In Spain the incidence of PCa was 70.75 cases per 100,000 males. Advanced
PCa has spread outside of the prostate capsule and may involve other parts of the
body. The aim of this study was to estimate the lifetime costs of a cohort of
advanced PCa patients diagnosed in Spain in 2012. METHODS: A partitioned economic
model was developed in EXCEL incorporating Spanish incidence, mortality, and cost
data supplemented with data from the international literature. Progression from
Stage III to Stage IV was permitted. Costs were discounted at the standard rate
of 3%. Lifetime costs were presented on an individual basis and for the entire
cohort of newly diagnosed Stage III and Stage IV PCa patients. RESULTS: Lifetime
costs for advanced PCa were ~?19,961 per patient (mean survival of 8.4 years).
Using the projected incident cases for 2012 (3047), the total cost for the
incident cohort of patients in 2012 would amount to ?61 million. These results
were more sensitive to changes in the ongoing costs (post-initial 12 months) of
Stage III PCa, the rate of progression from Stage III to Stage IV, and the
discount rate applied to costs. CONCLUSIONS: This study provides an estimate of
the lifetime costs of advanced PCa in Spain and a framework for further research.
The study is limited by the availability of long-term Spanish data and the need
to make inferences from international studies. However, until long-term
prospective or observational data do become available in Spain, based on the
assumptions, the current results indicate that the burden of advanced PCa in
Spain is substantial. Any treatments that could potentially reduce the economic
burden of the disease should be of interest to healthcare decision makers.
PMID- 24350998
TI - Prevalence and risk factors of intimate partner violence among pregnant women in
Japan.
AB - Intimate partner violence (IPV) during pregnancy can result in adverse outcomes
for both mothers and their infants. This cross-sectional study examined the
prevalence and risk factors of IPV associated with abuse during pregnancy via a
self-administered questionnaire completed by 302 healthy pregnant women.
Demographic information was also collected from medical records to analyze risk
factors for abuse. Of the 302 women, 48 (15.9%) were identified as experiencing
IPV. The identified risk factors were age over 30, multipara, previous abortion
experience, and male partner aged under 30.
PMID- 24350999
TI - The inherent ethical challenge of first-in-human pluripotent stem cell trials.
PMID- 24351000
TI - The potential of gene transfer for the treatment of osteoarthritis.
PMID- 24351001
TI - Will it be possible to generate kidney tissue from induced pluripotent stem cells
for regenerative therapy?
PMID- 24351004
TI - A new role for caspase in neural progenitor cell self-renewal.
PMID- 24351005
TI - Injectable gel graft for bone defect repair.
AB - AIM: To examine the performance of an injectable gel graft made of
transglutaminase (Tg)-crosslinked gelatin gel with BMP-2 (BMP-2-Tg-Gel) for bone
defect repair in animal models. MATERIALS & METHODS: BMP-2 mixed with gelatin gel
was crosslinked using Tg. The release of tethered BMP-2 through autocrine and
paracrine pathways was demonstrated by using C2C12 and NIH 3T3 cells,
respectively. BMP-2-Tg-Gel was injected into the induced cranial defect site.
After 14 days, the sample was removed for x-ray imaging and histological
evaluation. RESULTS: Our in vivo results demonstrated that the injectable Tg-Gel
with its osteoconductivity and controllable BMP-2 activity induced bone formation
in our rat models when tethered with BMP-2. CONCLUSION: Tg-Gel as an injectable
functional bone graft may enable the use of minimally invasive surgical
procedures to treat irregular-shaped bone defects. Furthermore, this novel
approach is capable of incorporating and controlling the release of therapeutic
agents that may advance the science of tissue regeneration.
PMID- 24351006
TI - Human embryonic stem cell-derived neural crest cells capable of expressing
markers of osteochondral or meningeal-choroid plexus differentiation.
AB - AIMS: The transcriptome and fate potential of three diverse human embryonic stem
cell-derived clonal embryonic progenitor cell lines with markers of cephalic
neural crest are compared when differentiated in the presence of combinations of
TGFbeta3, BMP4, SCF and HyStem-C matrices. MATERIALS & METHODS: The cell lines
E69 and T42 were compared with MEL2, using gene expression microarrays,
immunocytochemistry and ELISA. RESULTS: In the undifferentiated progenitor state,
each line displayed unique markers of cranial neural crest including TFAP2A and
CD24; however, none expressed distal HOX genes including HOXA2 or HOXB2, or the
mesenchymal stem cell marker CD74. The lines also showed diverse responses when
differentiated in the presence of exogenous BMP4, BMP4 and TGFbeta3, SCF, and SCF
and TGFbeta3. The clones E69 and T42 showed a profound capacity for expression of
endochondral ossification markers when differentiated in the presence of BMP4 and
TGFbeta3, choroid plexus markers in the presence of BMP4 alone, and
leptomeningeal markers when differentiated in SCF without TGFbeta3. CONCLUSION:
The clones E69 and T42 may represent a scalable source of primitive cranial
neural crest cells useful in the study of cranial embryology, and potentially
cell-based therapy.
PMID- 24351007
TI - Temporal HLA profiling and immunomodulatory effects of human adult bone marrow-
and adipose-derived mesenchymal stem cells.
AB - AIM: To investigate the temporal HLA expression profile and immunomodulatory
function of mesenchymal stem cells (MSCs) during in vitro expansion. MATERIALS &
METHODS: Adult bone marrow-derived MSCs (BMSCs) and adipose-derived MSCs (AMSCs)
were cultured and HLA class I and II mRNA expression were investigated during
serial expansion using semiquantitative reverse-transcription PCR. The
immunomodulatory properties of MSCs were monitored using peripheral blood
mononuclear cell (PBMC) proliferation and cytotoxicity assays. RESULTS:
Semiquantitative reverse-transcription PCR revealed that classical HLA class I
molecules were highly expressed in MSCs and remained relatively stable during
extended culture. Variable expression levels of HLA class II molecules were
detected in both BMSCs and AMSCs across passages. AMSCs were more resistant to
PBMC-mediated cytotoxicity and suppressed PBMC proliferation more than BMSCs,
although the effect was diminished with increasing passage. CONCLUSION: These
findings provide insight regarding the relationship between MSC passage number
and MSC immunosuppressive properties and suggest that AMSCs hold advantages over
BMSCs for immunomodulatory therapeutic purposes.
PMID- 24351008
TI - Regulating cell-based regenerative medicine: the challenges ahead.
AB - Those working in the regenerative medicine field currently face numerous
regulatory and related challenges. This Perspective captures some of the key
ideas of a UK-based working group drawn from academic, clinical and industrial
communities and also identifies some key steps that should be taken in the UK and
elsewhere to address these challenges.
PMID- 24351010
TI - Regenerative medicine and hair loss: how hair follicle culture has advanced our
understanding of treatment options for androgenetic alopecia.
AB - Many of the current drug therapies for androgenetic alopecia were discovered
serendipitously, with hair growth observed as an off-target effect when drugs
were used to treat a different disorder. Subsequently, several studies using
cultured cells have enabled identification of hair growth modulators with similar
properties to the currently available drugs, which may also provide clinical
benefit. In situations where the current therapeutics do not work, follicular
unit transplantation is an alternative surgical option. More recently, the
concept of follicular cell implantation, or hair follicle neogenesis, has been
attempted, exploiting the inherent properties of cultured hair follicle cells to
induce de novo hair growth in balding scalp. In this review, we discuss both the
advances in cell culture techniques that have led to a wider range of potential
therapeutics to promote hair growth, in addition to detailing current knowledge
on follicular cell implantation, and the challenges in making this approach a
reality.
PMID- 24351011
TI - Hype and expectations in tissue engineering.
AB - Scientific progress and the development of new technologies often incite
enthusiasm, both in scientists and the public at large, and this is especially
apparent in discussions of emerging medical technologies, such as tissue
engineering (TE). Future-oriented narratives typically discuss potential
applications with much hype and expectations. In this article, we analyze the
discourse on TE, its history and the promises present in the discourse
surrounding it. Subsequently, we regard discussions about implantable
bioartificial kidneys, and consider the concepts of hype and expectations in TE
in general. Finally, we discuss what ethically responsible choices should be made
in discussing TE to adequately deal with the scientific reality and public
expectations surrounding this technology.
PMID- 24351012
TI - Convergent and divergent pathways decoding hierarchical additive mechanisms in
treating cerebral ischemia-reperfusion injury.
AB - INTRODUCTION: Cerebral ischemia is considered to be a highly complex disease
resulting from the complicated interplay of multiple pathways. Disappointedly,
most of the previous studies were limited to a single gene or a single pathway.
The extent to which all involved pathways are translated into fusing mechanisms
of a combination therapy is of fundamental importance. AIMS: We report an
integrative strategy to reveal the additive mechanism that a combination (BJ) of
compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia
based on variation of pathways and functional communities. RESULTS: We identified
six pathways of BJ group that shared diverse additive index from 0.09 to 1, which
assembled broad cross talks from seven pathways of BA and 16 pathways of JA both
at horizontal and vertical levels. Besides a total of 60 overlapping functions as
a robust integration background among the three groups based on significantly
differential subnetworks, additive mechanism with strong confidence by networks
altered functions. CONCLUSIONS: These results provide strong evidence that the
additive mechanism is more complex than previously appreciated, and an
integrative analysis of pathways may suggest an important paradigm for revealing
pharmacological mechanisms underlying drug combinations.
PMID- 24351009
TI - Engineering muscle constructs for the creation of functional engineered
musculoskeletal tissue.
AB - Volumetric muscle loss (VML) is a disabling condition in which current clinical
procedures are suboptimal. The field of tissue engineering has many promising
strategies for the creation of functional skeletal muscle in vitro. However,
there are still two key limitations that prevent it from becoming a solution for
treating VML. First, engineered muscle tissue must be biocompatible to facilitate
muscle tissue regrowth without generating an immune response. Second, engineered
muscle constructs must be scaled up to facilitate replacement of clinically
relevant volumes of tissue (centimeters in diameter). There are currently no
tissue engineering strategies to produce tissue constructs that are both
biocompatible and large enough to facilitate clinical repair. However, recent
advances in tissue engineering using synthetic scaffolds, native scaffolds, or
scaffold-free approaches may lead to a solution for repair of VML injuries.
PMID- 24351013
TI - Dysfunctional endogenous pain modulation in patients with functional dyspepsia.
AB - BACKGROUND: Endogenous pain modulation (EPM) is central to the processing of
sensory information. Visceral and somatic EPM are abnormal in irritable bowel
syndrome, but have not been studied in functional dyspepsia (FD). METHODS:
Visceral EPM was assessed in 34 FD patients and 42 healthy controls. Gastric pain
was induced with oral capsaicin and EPM was studied by adding heterotopic thermal
foot stimulation or distraction by STROOP test. Somatic EPM was assessed using
foot heat stimulation with heterotopic hand electrical stimulation. KEY RESULTS:
Endogenous pain modulation by distraction reduced mean gastric pain by 11.9 on
the 0-100 visual analog scale (95% CI: 3.8-20.1) in controls (p = 0.006) and by
2.0 (-6.18 to 10.44) in FD (p = 0.6), with greater EPM in controls than in FD
(difference -13.3 [-26.1 to -0.5]; p = 0.04). Endogenous pain modulation by
heterotopic foot stimulation reduced gastric pain by 6.5 (-0.7 to 13.6) in
controls (p = 0.07) and by 7.1 (-2.29 to 16.47) in FD (p = 0.1), with no
significant difference in EPM between controls and FD (-2.0 [-14.5 to 10.5]; p =
0.75). In patients with prominent FD pain, greater pain correlated with decreased
visceral EPM by distraction (r = 0.51, p = 0.04). Somatic EPM by heterotopic
stimulation significantly decreased foot pain in controls (p = 0.004), but not in
FD (p = 0.80). CONCLUSIONS & INFERENCES: In FD, visceral pain modulation by
distraction was dysfunctional compared to controls. Somatic pain modulation was
also decreased in FD. These data and the correlation of abnormal pain modulation
by distraction with clinical pain in pain-predominant FD suggest a potential
pathophysiological significance of abnormal pain modulation in FD.
PMID- 24351014
TI - Reproductive character displacement of epicuticular compounds and their
contribution to mate choice in Drosophila subquinaria and Drosophila recens.
AB - Interactions between species can alter selection on sexual displays used in mate
choice within species. Here we study the epicuticular pheromones of two
Drosophila species that overlap partially in geographic range and are
incompletely reproductively isolated. Drosophila subquinaria shows a pattern of
reproductive character displacement against Drosophila recens, and partial
behavioral isolation between conspecific sympatric versus allopatric populations,
whereas D. recens shows no such variation in mate choice. First, using
manipulative perfuming experiments, we show that females use pheromones as
signals for mate discrimination both between species and among populations of D.
subquinaria. Second, we show that patterns of variation in epicuticular
compounds, both across populations and between species, are consistent with those
previously shown for mating probabilities: pheromone compositions differ between
populations of D. subquinaria that are allopatric versus sympatric with D.
recens, but are similar across populations of D. recens regardless of overlap
with D. subquinaria. We also identify differences in pheromone composition among
allopatric regions of D. subquinaria. In sum, our results suggest that
epicuticular compounds are key signals used by females during mate recognition,
and that these traits have diverged among D. subquinaria populations in response
to reinforcing selection generated by the presence of D. recens.
PMID- 24351017
TI - Use of oral anticoagulants in atrial fibrillation is highly variable and only
weakly associated with estimated stroke risk: cross-sectional population database
study.
AB - BACKGROUND: Current international guidelines promote the use of stroke risk
stratification tools to inform decision making about oral anticoagulant (OAC) use
in atrial fibrillation (AF). OBJECTIVES: To examine (a) differences between
CHADS2 and CHA2DS2VASc in classifying stroke risk in a primary care population of
AF patients; (b) patterns of use of antithrombotics by stroke risk; and (c)
patient and practice characteristics associated with use of oral anticoagulants
in patients with AF. METHODS: Cross-sectional multilevel modelling study of all
patients with AF and without rheumatic heart disease or valve replacement (n = 21
564) from 315 Scottish General Practices. RESULTS: (a) CHADS2 characterized 30.3%
in the intermediate and 53.8% in the high-risk category, compared to CHA2DS2VASC
only 9.7% intermediate and 85.1% high-risk. (b) Of included patients, 17.8% were
currently not prescribed any antithrombotic and 43.3% were on OAC. OAC use was
only weakly related to stroke risk. (c) Patients with paroxysmal AF and those
with dementia and previous peptic ulcer (adjusted ORs 0.26, 0.25 and 0.79) were
less likely to be prescribed OAC. OAC use varied over five-fold between practices
after adjustment for patient case mix, with remote and non-training practices and
those with high levels of high-risk prescribing being more likely to prescribe
OAC. CONCLUSION: Evidence was found of both underuse and overuse of OAC in
patients with AF. Promoting instruments for stroke risk assessment in AF is a
plausible but untested strategy to improve decision making in AF, and its impact
on OAC prescribing and patient outcomes should be evaluated in pragmatic trials.
PMID- 24351015
TI - CD56negCD16+ NK cells are activated mature NK cells with impaired effector
function during HIV-1 infection.
AB - BACKGROUND: A subset of CD3(neg)CD56(neg)CD16+ Natural Killer (NK) cells is
highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1
pathogenesis remains unclear. The lack of NK cell lineage-specific markers has
complicated the study of minor NK cell subpopulations. RESULTS: Using CD7 as an
additional NK cell marker, we found that CD3(neg)CD56(neg)CD16+ cells are a
heterogeneous population comprised of CD7+ NK cells and CD7(neg) non-classical
myeloid cells. CD7+CD56(neg)CD16+ NK cells are significantly expanded in HIV-1
infection. CD7+CD56(neg)CD16+ NK cells are mature and express KIRs, the C-type
lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar
to CD7+CD56+CD16+ NK cells. CD7+CD56(neg) NK cells in healthy donors produced
minimal IFNgamma following K562 target cell or IL-12 plus IL-18 stimulation;
however, they degranulated in response to K562 stimulation similar to CD7+CD56+
NK cells. HIV-1 infection resulted in reduced IFNgamma secretion following K562
or cytokine stimulation by both NK cell subsets compared to healthy donors.
Decreased granzyme B and perforin expression and increased expression of CD107a
in the absence of stimulation, particularly in HIV-1-infected subjects, suggest
that CD7+CD56(neg)CD16+ NK cells may have recently engaged target cells.
Furthermore, CD7+CD56(neg)CD16+ NK cells have significantly increased expression
of CD95, a marker of NK cell activation. CONCLUSIONS: Taken together,
CD7+CD56(neg)CD16+ NK cells are activated, mature NK cells that may have recently
engaged target cells.
PMID- 24351018
TI - Diabetes mellitus--a global pandemic. Keynote lecture presented at the Wonca
conference in Prague in June 2013.
AB - The huge increase in the number of people with diabetes mellitus over recent
decades raises questions about early diagnosis, intensive treatment and primary
prevention. Insulin and oral agents' discoveries have improved the prognosis of
patients with diabetes, but vascular complications still remain the main cause of
increased morbidity and mortality. Therefore, strategies oriented to the
prevention of diabetes and its complications are the main goal in the care of
diabetic patients. Further intensive efforts will be necessary not only by the
community of physicians and scientists, but also governments, industry, non
governmental organizations and by individuals engaging in a healthier lifestyle.
Better diabetes awareness and lifestyle changes may significantly reduce the main
problems with diabetes.
PMID- 24351019
TI - Photodamage in a mitochondrial membrane model modulated by the topology of
cationic and anionic meso-tetrakis porphyrin free bases.
AB - The photodynamic effects of the cationic TMPyP (meso-tetrakis [N-methyl-4
pyridyl]porphyrin) and the anionic TPPS4 (meso-tetrakis[4
sulfonatophenyl]porphyrin) against PC/CL phosphatidylcholine/cardiolipin (85/15%)
membranes were probed to address the influence of phorphyrin binding on lipid
damage. Electronic absorption spectroscopy and zeta potential measurements
demonstrated that only TMPyP binds to PC/CL large unilamellar vesicles (LUVs).
The photodamage after irradiation with visible light was analyzed by dosages of
lipid peroxides (LOOH) and thiobarbituric reactive substance and by a contrast
phase image of the giant unilamellar vesicles (GUVs). Damage to LUVs and GUVs
promoted by TMPyP and TPPS4 were qualitatively and quantitatively different. The
cationic porphyrin promoted damage more extensive and faster. The increase in
LOOH was higher in the presence of D2O, and was impaired by sodium azide and
sorbic acid. The effect of D2O was higher for TPPS4 as the photosensitizer. The
use of DCFH demonstrated that liposomes prevent the photobleaching of TMPyP. The
results are consistent with a more stable TMPyP that generates long-lived singlet
oxygen preferentially partitioned in the bilayer. Conversely, TPPS4 generates
singlet oxygen in the bulk whose lifetime is increased in D2O. Therefore, the
affinity of the porphyrin to the membrane modulates the rate, type and degree of
lipid damage.
PMID- 24351020
TI - Cost-effectiveness analysis of a postoperative clinical care pathway in head and
neck surgery with microvascular reconstruction.
AB - BACKGROUND: The objective of this study is to evaluate the cost-effectiveness of
a postoperative clinical care pathway for patients undergoing major head and neck
oncologic surgery with microvascular reconstruction. METHODS: This is a
comparative trial of a prospective treatment group managed on a postoperative
clinical care pathway and a historical group managed prior to pathway
implementation. Effectiveness outcomes evaluated were total hospital days, return
to OR, readmission to ICU and rate of pulmonary complications. Costing
perspective was from the government payer. RESULTS: 118 patients were included in
the study. All outcomes demonstrated that the postoperative pathway group was
both more effective and less costly, and is therefore a dominant clinical
intervention. The overall mean pre- and post-pathway costs are $22,733 and
$16,564 per patient, respectively. The incremental cost reduction associated with
the postoperative pathway was $6,169 per patient. CONCLUSION: Implementing the
postoperative clinical care pathway in patients undergoing head and neck
oncologic surgery with reconstruction resulted in improved clinical outcomes and
reduced costs.
PMID- 24351021
TI - Proteomics in immunity and herpes simplex encephalitis.
AB - The genetic theory of infectious diseases has proposed that susceptibility to
life-threatening infectious diseases in childhood, occurring in the course of
primary infection, results mostly from individually rare but collectively diverse
single-gene variants. Recent evidence of an ever-expanding spectrum of genes
involved in susceptibility to infectious disease indicates that the paradigm has
important implications for diagnosis and treatment. One such pathology is
childhood herpes simplex encephalitis, which shows a pattern of rare but diverse
disease-disposing genetic variants. The present report shows how proteomics can
help to understand susceptibility to childhood herpes simplex encephalitis and
other viral infections, suggests that proteomics may have a particularly
important role to play, emphasizes that variation over the population is a
critical issue for proteomics and notes some new challenges for proteomics and
related bioinformatics tools in the context of rare but diverse genetic defects.
PMID- 24351023
TI - Thiamine and Hashimoto's thyroiditis: a report of three cases.
AB - OBJECTIVES: In a previous study on fatigue and related disorders in inflammatory
bowel disease (IBD), we observed that IBD patients improved after treatment with
high-dose thiamine. We hypothesized that the chronic fatigue accompanying
inflammatory and autoimmune diseases is the clinical manifestation of a mild
thiamine deficiency that is probably due to a dysfunction of the intracellular
transport or to enzymatic abnormalities. Hashimoto's thyroiditis is both a common
automimmune disease and cause of hypothyroidism. Although levothyroxine, a
thyroid hormone, is the treatment of choice for hypothyroidism, a significant
number of patients on thyroid hormone replacement therapy report not feeling well
despite having thyroid function tests within the healthy range. Based on our
hypothesis, we started treating the fatigue in patients affected by Hashimoto's
thyroiditis and taking a thyroid hormone with thiamine. This is a report of the
outcomes of three cases in which the fatigue component reported by patients with
Hashimoto's thyroiditis was treated with thiamine. DESIGN: Three patients on
thyroid hormone replacement because of Hashimoto's thyroiditis were treated for
the fatigue component of the disease from May to July 2011. Fatigue was measured
using the Fatigue Severity Scale. Free thiamine in the serum and thiamine
pyrophosphate in red cells were tested before and after the therapy. All three
patients received oral (600 mg/day) or parenteral (100 mg/ml every four days)
doses of thiamine. RESULTS: Treatment with thiamine led to partial or complete
regression of the fatigue within a few hours or days. CONCLUSION: As the
administration of thiamine led to a partial or complete regression of the fatigue
and related disorders, it is reasonable to infer that the administration of large
quantities of thiamine restores thiamine-dependent processes. The mild thiamine
deficiency suggested by fatigue and related disorders may be due a dysfunction of
the intracellular transport of thiamine or to enzymatic abnormalities most likely
related to the autoimmune process of the disease.
PMID- 24351022
TI - The Cdc48-Vms1 complex maintains 26S proteasome architecture.
AB - The 26S proteasome is responsible for most regulated protein turnover and for the
degradation of aberrant proteins in eukaryotes. The assembly of this ~2.5 MDa
multicatalytic protease requires several dedicated chaperones and, once
assembled, substrate selectivity is mediated by ubiquitin conjugation. After
modification with ubiquitin, substrates are escorted to the proteasome by myriad
factors, including Cdc48 (cell-division cycle 48). Cdc48 also associates with
numerous cofactors, but, to date, it is unclear whether each cofactor facilitates
proteasome delivery. We discovered that yeast lacking a conserved Cdc48 cofactor,
Vms1 [VCP (valosin-containing protein)/Cdc48-associated mitochondrial stress
responsive], accumulate proteasome-targeted ubiquitinated proteins. Vms1 mutant
cells also contain elevated levels of unassembled 20S proteasome core particles
and select 19S cap subunits. In addition, we found that the ability of Vms1 to
support 26S proteasome assembly requires Cdc48 interaction, and that the loss of
Vms1 reduced 26S proteasome levels and cell viability after prolonged culture in
the stationary phase. The results of the present study highlight an unexpected
link between the Cdc48-Vms1 complex and the preservation of proteasome
architecture, and indicate how perturbed proteasome assembly affects the turnover
of ubiquitinated proteins and maintains viability in aging cells.
PMID- 24351024
TI - The importance and necessity of establishing technical specifications for the
registration of Traditional Chinese Medicine clinical studies.
PMID- 24351025
TI - Pharmacological management of cardiovascular conditions and diabetes in older
adults with HIV infection.
AB - This review looks at the evidence for potential and theoretical risks of
combining antiretroviral treatment with drugs prescribed for cardiovascular
disease and diabetes. These conditions are common in the HIV-infected population
as a result of ageing and the increased risk associated with both HIV infection
and antiretroviral intake.
PMID- 24351026
TI - Evaluation of the novel ultrasound score for large joints in psoriatic arthritis
and ankylosing spondylitis: six month experience in daily clinical practice.
AB - BACKGROUND: To evaluate the utility of the recently introduced SOLAR score
(sonography of large joints in Rheumatology), which has been validated in RA
patients, in a cohort of patients with Psoriatic Arthritis (PsA) and Ankylosing
Spondylitis (AS) presenting with involvement of large peripheral joints. METHODS:
The recently established SOLAR score has been designed to determine the degree of
inflammation in the shoulder, the elbow, the hip and the knee joint in patients
suffering from RA. Since large joints are frequently involved in PsA and AS,
synovitis and synovial vascularity were scored semiquantitatively (grade 0-3) by
grey scale (GSUS) and power Doppler ultrasound (PDUS) utilizing the validated
scoring system. Each joint was scanned from different angles, the knee joint for
example was divided into four areas to score for synovitis: the suprapatellar
longitudinal, the medial longitudinal, the lateral longitudinal, and the
posterior region. Each area was scored from 0-3, so a maximum score of 12 could
be achieved. PsA and AS patients presenting with peripheral joint disease
involving large joints were examined at baseline, 3 and 6 months after initiation
of local or systemic therapy (DMARDs/Biologics). For evaluation of the
inflammatory status, the erythrocyte sedimentation rate (ESR) was determined.
RESULTS: A cohort of 126 patients were enclosed, and 83 of these were followed
for 6 months. At baseline before modification of the therapy, patients received
DMARDs (n = 83), DMARDs plus biologics (n = 30), or biologic monotherapy (n =
29). Following intervention, all US scores demonstrated a marked improvement. The
GSUS and the PDUS scores for all joint areas, except the PDUS score of the hip,
exhibited a significant improvement (p < 0.05), while the GSUS of the knee showed
even a highly significant (p < 0.001) change. The ESR displayed a significant
decrease from 27 to 19 mm (p < 0.002) representing good treatment response.
CONCLUSION: The SOLAR score, which has been recently introduced for RA patients,
is a very suitable instrument for the qualitative and quantitative evaluation of
large joint involvement in PsA and AS patients and allows for treatment
monitoring.
PMID- 24351027
TI - Relieving my discomforts safely: the experiences of discontinuing HRT among
menopausal women.
AB - AIM AND OBJECTIVES: To generate a descriptive theoretical framework about the
experiences of women who discontinued hormone replacement therapy. BACKGROUND:
Some menopausal women would depend on hormone replacement therapy for relieving
their menopausal symptoms. However, most of them feared of hormone replacement
therapy's side effects and tried to discontinue hormone replacement therapy
immediately. How did these women self-manage their discomforts without using
dependent medicine--hormone replacement therapy? There are few studies conducted
on this issue. DESIGN: A grounded theory research was applied. METHODS: Nineteen
Taiwanese women discontinuing hormone replacement therapy for three months, aged
45 to 67 years, participated in face-to-face audio-taped interviews. Data
collection, and coding of interviews, and data analysis occurred simultaneously.
All conversations were audio-recorded and then transcribed as verbatim text. The
constant comparative method was used to analyse the interview data. RESULTS:
'Relieving my discomforts safely' was the core theme for describing and guiding
the process of discontinuing hormone replacement therapy. 'Immediately
discontinuing hormone replacement therapy--it would hurt my body' was identified
as the antecedent condition. Analyses showed five dimensions to the women's
relieving my discomforts safely: (1) symptoms bothered me again, (2) negative
emotions, (3) learning to let it go, (4) trying to use nonhormone replacement
therapy or products and (5) choosing safely therapies as first priority. Finally,
some women would choose their suitable nonhormone replacement therapy way, and
some women would reuse hormone replacement therapy cautiously. CONCLUSIONS:
'Relieving my discomforts safely' was the first-priority consideration for the
menopausal women discontinuing hormone replacement therapy. It is the challenge
to establish the health programme or management for helping these women felt
safety and security to relieve their menopausal symptoms by using hormone
replacement therapy or nonhormone replacement therapy. RELEVANCE TO CLINICAL
PRACTICE: Healthcare providers need to empower women the rights of decision
making of using hormone replacement therapy and assist them in monitoring their
health status to reduce their fear and uncertainty.
PMID- 24351028
TI - Cost minimization analysis of beta-blocker at the time of CT imaging for
suspected of coronary heart disease in Japan.
AB - OBJECTIVES: To conduct a cost-minimization analysis of landiolol for CT diagnosis
of coronary heart diseases in patients with tachycardia in Japan. METHODS: A
decision-tree model was constructed to analyze costs from the healthcare payer's
perspective. Drug costs and diagnosis costs, computer tomography coronary
angiography (CTCA), and coronary angiography (CAG), are adopted to the model.
Landiolol is administered only to slow the heart rate to take CT images
appropriately. Since some trials proved that there was no difference between
landiolol and placebo in terms of efficacy and safety, this study conducted cost
minimization analysis. Of those suspected of coronary heart diseases, 22.5% are
thought to be taking beta-blockers. The success rates for CT scanning for
landiolol and placebo, derived from domestic trial data, were 81.4% (96/118, 77.8
84.9%) and 54.2% (64/118, 49.7-58.8%). Patients who failed to take a CT image
were thought to take CAG. The healthcare cost was derived from a Japanese fee
schedule. Costs of landiolol, CT imaging, and CAG are JPY2634 (USD1 = JPY100, as
of November 20, 2013), JPY38,116, and JPY101,322, respectively. The positive rate
for CAG, derived from domestic trial data, was 37.1% (33/89, 32.0-42.2%). Various
sensitivity analyses, both univariate and probabilistic ones, were conducted.
RESULTS: In the base case analysis, expected costs per patient for landiolol and
placebo were JPY78,956 and JPY82,232, respectively. In budget impact analysis,
81,062 patients are eligible for landiolol and it can save JPY266million for
whole patients. Sensitivity analyses suggested the robustness of the results.
LIMITATIONS: This study did not consider any adverse effects in the decision-tree
model. This model was developed especially for measuring the cost-saving effect
of landiolol, through decreasing the number of patients who require CAG, due to
imaging failure. CONCLUSIONS: Landiolol for CTCA diagnosis in patients suspected
of coronary heart disease with tachycardia is thought to be cost saving.
PMID- 24351029
TI - Structure and shape effects of molecular glue on supramolecular tubulin
assemblies.
AB - The possibility to arrange biological molecules into ordered nanostructures is an
important issue in nano- and biotechnology. Nature offers a wide range of
molecular "bricks" (e.g., proteins, oligonucleotides, etc.) that spontaneously
assemble into more complex hierarchical systems with unique functionalities. Such
molecular building blocks can be also used for the construction of nanomaterials
with peculiar properties (e.g., DNA origami). In some cases, molecular glues able
to bind biomolecules and to induce their assembly can be used to control the
final structure and properties in a convenient way. Here we provide molecular
level description of how molecular glues designed to stick to the surface of
microtubules (MTs) can control and transform the alpha/beta-tubulin assembly upon
temperature decreasing. By means of all-atom molecular dynamics (MD) simulations,
we compared the adhesion to the MT surface of three molecular glues bearing the
same guanidinium ion surface adhesive groups, but having different architecture,
i.e., linear or dendritic backbone. Our evidence demonstrates that the adhesive
properties of the different molecular glues are dependent on the shape they
assume in solution. In particular, adhesion data from our MD simulations explain
how globular- or linear-like molecular glues respectively stabilize MTs or
transform them into a well-defined array of alpha/beta-tubulin rings at 15
degrees C, where MTs naturally depolymerize. The comprehension of the MT
transformation mechanism provides a useful rationale for designing ad hoc
molecular glues to obtain ordered protein nanostructures from different
biological materials.
PMID- 24351030
TI - Murine cardiosphere-derived cells are impaired by age but not by cardiac
dystrophic dysfunction.
AB - To be clinically relevant as a therapy for heart failure, endogenous progenitor
cells must be isolated and expanded from aged and/or diseased tissue. Here, we
investigated the effect of age and cardiac impairment resulting from lack of
dystrophin on murine cardiosphere-derived cells (CDCs). CDCs were isolated and
expanded from atrial biopsies from wild-type mice aged 1.5, 6, 18, and 24 months
and from mdx mice aged 6 and 18 months. Cardiac function was measured in mdx mice
and age-matched wild-type mice using high-resolution cine magnetic resonance
imaging. CDCs could be isolated and expanded from all mice, however, the number
of cells obtained, and their regenerative potential, decreased with age, as
demonstrated by decreased expression of stem cell markers, c-kit and Sca-1, and
decreased cell proliferation, migration, clonogenicity, and differentiation. Six
month-old mdx mice showed right ventricular (RV) dilation and reduced RV ejection
fraction (EF) in comparison to wild-type mice. Older mdx mice displayed
significant RV and left ventricular dilation and decreased EF in both ventricles,
compared with age-matched wild-type mice. Mdx mouse hearts contained
significantly more fibrotic tissue than age-matched wild-type mouse hearts.
However, CDCs isolated from mice aged 6 and 18 months had the same number and
regenerative potential from mdx mice and age-matched wild-type mice. Thus, the
cardiac progenitor cell population is impaired by age but is not substantially
altered by the progressive deterioration in function of the dystrophic heart.
PMID- 24351031
TI - Inhibition of 5-oxo-6,8,11,14-eicosatetraenoic acid-induced activation of
neutrophils and eosinophils by novel indole OXE receptor antagonists.
AB - 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a 5-lipoxygenase product
that is a potent granulocyte chemoattractant, which induces the infiltration of
eosinophils into human skin when injected intradermally. It could therefore be an
important proinflammatory mediator in eosinophilic diseases such as asthma and
allergic rhinitis, and the OXE receptor, which mediates its actions, is therefore
an attractive drug target. Using a structure-based approach in which substituents
mimicking the essential polar (C1-C5) and hydrophobic (C15-C20) regions of 5-oxo
ETE were incorporated on an indole scaffold, we identified two potent selective
OXE antagonists with IC50 values of about 30 nM. Neither compound displayed
agonist activity and both inhibited 5-oxo-ETE-induced chemotaxis and actin
polymerization and were relatively resistant to metabolism by rat liver
homogenates. The active enantiomers of these racemic antagonists were even more
potent, with IC50 values of <10 nM. These selective OXE antagonists could
potentially be useful therapeutic agents in allergic diseases such as asthma.
PMID- 24351032
TI - Effect of body weight loss on cardiopulmonary function assessed by 6-minute walk
test and arterial blood gas analysis in obese dogs.
AB - BACKGROUND: Few studies show the detrimental effect of canine obesity on
cardiopulmonary function (CPF). The 6-Minute Walk Test (6MWT) is a noninvasive
exercise test easy to perform in clinical settings. OBJECTIVE: The aim of this
study was to investigate the effect of obesity and body weight loss (BWL) on CPF
assessed by the 6MWT and arterial blood gas analysis. ANIMALS: Six experimental
Beagles and 9 privately owned obese dogs were enrolled in a diet-induced BWL
program. METHODS: Arterial blood gas analysis and 6MWT were repeated in obese
subjects (BCS 8-9/9), in the middle of BWL (overweight, BCS 6-7/9), and in lean
dogs (BCS 5/9). Heart rate (HRp) and oxygen saturation (SpO2 ) were measured by
pulse oximetry before the 6MWT, at midtest, and during a 5-minute recovery
period. RESULTS: Twelve dogs completed the BWL program (initial BW, 27.3 +/- 2.9
kg; final BW, 20.85 +/- 2.9, lsmeans +/- SE, P <= .001). BWL caused a significant
increase in 6MWT walked distance (WD; obese: 509 +/- 35 m; overweight: 575 +/- 36
m; lean: 589 +/- 36 m; P <= .05). Resting arterial blood gas results were not
influenced by BWL. Including all time points, obese dogs showed higher HRp and
lower SpO2 compared to overweight and lean dogs. SpO2 at the end of the walk was
significantly lower in obese dogs. CONCLUSION AND CLINICAL IMPORTANCE: Obesity
negatively affects 6MWT performances in dogs. The 6MWT may be used to demonstrate
the efficacy of BWL to improve CPF and quality of life in obese dogs. Although
BWL induced significant improvement of cardiopulmonary parameters before ideal
BW, WD improved until the end of the BWL program.
PMID- 24351033
TI - A cross-generational study of contraception and reproductive health among
Sudanese and Eritrean women in Brisbane, Australia.
AB - This study conducted in Brisbane, Australia, was undertaken with a cross-section
of Sudanese and Eritrean mothers and daughters. We explored and documented the
women's intergenerational experiences and knowledge of reproductive health and
contraception. Underpinned by a qualitative approach, focus group discussions
were undertaken along with key informant interviews with health and multicultural
sector professionals. Through examination of knowledge shared, the analysis
distilled key aspects of intergenerational fears, cultural safety, and health.
Participants proposed recommendations on how refugee and migrant women in
Australia and resettled countries globally can more effectively and holistically
exercise their sexual and reproductive health rights.
PMID- 24351034
TI - Diversification and gene flow in nascent lineages of island and mainland North
American tree squirrels (Tamiasciurus).
AB - Pleistocene climate cycles and glaciations had profound impacts on taxon
diversification in the Boreal Forest Biome. Using population genetic analyses
with multilocus data, we examined diversification, isolation, and hybridization
in two sibling species of tree squirrels (Tamiasciurus douglasii and Tamiasciurus
hudsonicus) with special attention to the geographically and genetically
enigmatic population of T. hudsonicus on Vancouver Island, Canada. The two
species differentiated only about 500,000 years ago, in the Late Pleistocene. The
island population is phylogenetically nested within T. hudsonicus according to
our nuclear analysis but within T. douglasii according to mitochondrial DNA. This
conflict is more likely due to historical hybridization than to incomplete
lineage sorting, and it appears that bidirectional gene flow occurred between the
island population and both species on the mainland. This interpretation of our
genetic analyses is consistent with our bioclimatic modeling, which demonstrates
that both species were able to occupy this region throughout the Late
Pleistocene. The divergence of the island population 40,000 years ago suggests
that tree squirrels persisted in a refugium on Vancouver Island at the last
glacial maximum, 20,000 years ago. Our observations demonstrate how Pleistocene
climate change and habitat shifts have created incipient divergence in the
presence of gene flow. Sequence data have been archived in GenBank-accession
numbers: KF882736-KF885216.
PMID- 24351035
TI - Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a
systematic review and meta-analysis.
AB - BACKGROUND: Treatment options for constipation-predominant irritable bowel
syndrome (IBS-C) are limited. While linaclotide improved IBS-C symptoms in
randomized controlled trials (RCTs), results vary among studies and the magnitude
of benefit is unclear. METHODS: Two investigators independently extracted data on
study participants, methods and outcomes (i.e., symptoms, quality of life, and
adverse events) from eligible articles i.e., RCTs comparing linaclotide with
placebo in adult patients with IBS-C with a follow-up of 12 weeks or longer. The
grading of recommendations assessment, development and evaluation (GRADE)
methodology was used to rate the quality of evidence. KEY RESULTS: Of 182
identified citations, three RCTs enrolling 1773 patients met the inclusion
criteria. Compared with placebo, fewer patients on linaclotide failed to achieve
responses i.e., FDA endpoint (1604 patients, risk ratio [RR] = 0.80; 95%CI 0.76
0.85), adequate IBS symptom relief (1773 patients, RR = 0.73; 95%CI 0.65-0.82),
and clinically meaningful improvement in IBS-QOL (1659 patients, RR = 0.78; 95%CI
0.72-0.86). The incidence of diarrhea leading to discontinuation of treatment was
higher for linaclotide (1773 patients, RR = 14.75; 95%CI 4.04-53.81). The quality
of evidence was rated as moderate for FDA endpoint and adequate relief response,
high for diarrhea, and low for IBS-QOL. Generalizability may be limited by the
study population (i.e., predominantly white female patients), lack of data
regarding prior therapy, and availability of few RCTs. The number of patients is
insufficient to identify rare adverse events. CONCLUSIONS & INFERENCES:
Linaclotide is moderately effective in improving symptoms of IBS-C with diarrhea
being the major side effect. Further studies are needed to evaluate the long-term
efficacy and safety of linaclotide for IBS-C.
PMID- 24351036
TI - Roles of interfacial modifiers in hybrid solar cells: inorganic/polymer bilayer
vs inorganic/polymer:fullerene bulk heterojunction.
AB - Hybrid solar cells (HSCs) incorporating both organic and inorganic materials
typically have significant interfacial issues which can significantly limit the
device efficiency by allowing charge recombination, macroscopic phase separation,
and nonideal contact. All these issues can be mitigated by applying carefully
designed interfacial modifiers (IMs). In an attempt to further understand the
function of these IMs, we investigated two IMs in two different HSCs structures:
an inverted bilayer HSC of ZnO:poly(3-hexylthiophene) (P3HT) and an inverted bulk
heterojunction (BHJ) solar cell of ZnO/P3HT:[6,6]-phenyl C61-butyric acid methyl
ester (PCBM). In the former device configuration, ZnO serves as the n-type
semiconductor, while in the latter device configuration, it functions as an
electron transport layer (ETL)/hole blocking layer (HBL). In the ZnO:P3HT bilayer
device, after the interfacial modification, a power conversion efficiency (PCE)
of 0.42% with improved Voc and FF and a significantly increased Jsc was obtained.
In the ZnO/P3HT:PCBM based BHJ device, including IMs also improved the PCE to
4.69% with an increase in Voc and FF. Our work clearly demonstrates that IMs help
to reduce both the charge recombination and leakage current by minimizing the
number of defect sites and traps and to increase the compatibility of hydrophilic
ZnO with the organic layers. Furthermore, the major role of IMs depends on the
function of ZnO in different device configurations, either as n-type
semiconductor in bilayer devices or as ETL/HBL in BHJ devices. We conclude by
offering insights for designing ideal IMs in future efforts, in order to achieve
high-efficiency in both ZnO:polymer bilayer structure and ZnO/polymer:PCBM BHJ
devices.
PMID- 24351037
TI - Possible mechanism involved in the antinociceptive activity of dimer of
paederosidic acid and paederosidic acid methyl ester in mice.
PMID- 24351038
TI - Acidic retinoids in small amounts promote retinyl ester formation in neonatal
lung, with transient increases in retinoid homeostatic gene expression.
AB - BACKGROUND: Mixing a small proportion, 10%, of retinoic acid (RA) into an oral
dose of vitamin A (VA) has been shown to markedly increase retinol uptake and
retinyl ester (RE) formation in the neonatal lung, as compared to VA given alone.
Concomitantly, several retinoid homeostatic genes, lecithin:retinol
acyltransferase (LRAT), RA-4-hydroxylase (CYP26B1), and stimulated by retinoic
acid gene-6 (STRA6) were upregulated. However, whether multiple doses may act
accumulatively and whether less than 10% RA can be used has not been determined.
METHODS: Neonatal rats were treated once on postnatal day (PD) 4 or PD14 with VA
alone or VA combined with 10% RA (VARA10%) or a stable analog, Am580 (VAAm10%),
or they were treated with multiple doses on PD4, 7, 11, and 14. RESULTS: RE
increased cumulatively with multiple dosing. However, LRAT, CYP26B1 and STRA6
mRNA levels were similar for single and multiple treatments, indicating a
transient noncumulative impact on gene expression. Lung RE was elevated with as
little as 0.5% RA (P < 0.05) in a single dosing study. Whereas all concentrations
of VARA elevated lung RE in single dosing studies, only 10% RA increased lung RE
after multiple dosing, suggesting an attenuation of RA action with repeated
dosing. In contrast, VAAm10%, 2%, and 1% all significantly increased lung RE
after multiple doses (P < 0.05), while also increasing the expression of LRAT and
CYP26B1. CONCLUSIONS: These results indicate that the neonatal lung is very
sensitive to acidic retinoid exposure and suggest that a VA combined with a very
small fraction of acidic retinoid could be effective in increasing the lung's
storage pool of VA.
PMID- 24351039
TI - Land-use efficiency of big solar.
AB - As utility-scale solar energy (USSE) systems increase in size and numbers
globally, there is a growing interest in understanding environmental interactions
between solar energy development and land-use decisions. Maximizing the efficient
use of land for USSE is one of the major challenges in realizing the full
potential of solar energy; however, the land-use efficiency (LUE; Wm(-2)) of USSE
remains ambiguous. We quantified the capacity-based LUE of 183 USSE installations
(>20 MW; planned, under construction, and operating) using California as a case
study. In California, USSE installations are concentrated in the Central Valley
and interior regions of southern California and have a LUE of 35.0 Wm(-2). The
installations occupy approximately 86,000 ha and more land is allocated for
photovoltaic schemes (72 294 ha) than for concentrating solar power (13,604 ha).
Photovoltaic installations are greater in abundance (93%) than concentrating
solar power, but technology type and nameplate capacity has no impact on capacity
based LUE. More USSE installations are on private land (80%) and have a
significantly greater LUE (35.8 Wm(-2)) than installations on public land (25.4
Wm(-2)). Our findings can be used to better understand and improve the LUE of
USSE, thereby maximizing economic, energetic, and environmental returns on
investments.
PMID- 24351040
TI - Highly selective off-on fluorescent probe for imaging thioredoxin reductase in
living cells.
AB - The first fluorescent probe for mammalian thioredoxin reductase (TrxR), TRFS
green, was designed, synthesized, and fully evaluated. The probe features a 1,2
dithiolane scaffold with a quenched naphthalimide fluorophore. TRFS-green
displays a green fluorescence off-on change induced by the TrxR-mediated
disulfide cleavage and subsequent intramolecular cyclization to liberate the
masked naphthalimide fluorophore. It was demonstrated in vitro that TRFS-green
manifests high selectivity toward TrxR over other related enzymes and various
small molecule thiols as well as biological reducing molecules. HPLC analyses
indicated that TRFS-green was exclusively converted to naphthalimide catalyzed by
TrxR. The ability in triggering on the fluorescence signal by cellular protein
extracts correlates well with the endogenous TrxR activity in different cells.
Furthermore, inhibition of TrxR by 2,4-dinitrochlorobenzene or depletion of TrxR
by immunoprecipitation remarkably decreases the reduction of TRFS-green by
cellular protein extracts. Finally, TRFS-green was successfully applied in
imaging TrxR activity in living cells. The fluorescence signal of TRFS-green in
living cells was inhibited by pretreating the cells with TrxR inhibitor in a dose
dependent manner, potentiating the development of living cell-based screening
assay for identifying TrxR inhibitors. We expect the novel fluorescent probe TRFS
green would facilitate the discovery of TrxR-targeting small molecules for
potential therapeutic agents and provide significant advances in understanding
the physiological/pathophysiological functions of TrxR in vivo.
PMID- 24351041
TI - The role of neural precursor cells and self assembling peptides in nerve
regeneration.
AB - OBJECTIVE: Cranial nerve injury involves loss of central neural cells in the
brain stem and surrounding support matrix, leading to severe functional
impairment. Therapeutically targeting cellular replacement and enhancing
structural support may promote neural regeneration. We examined the combinatorial
effect of neural precursor cells (NPC) and self assembling peptide (SAP)
administration on nerve regeneration. METHODS: Nerve injury was induced by clip
compression of the rodent spinal cord. SAPs were injected immediately into the
injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly
and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on
cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were
measured at week 11 to assess nerve conduction and Kaplan Meier curves were
created to compare survival estimates. RESULTS: NPCs and SAPs were distributed
both caudal and rostral to the injury site. Behavioral analysis showed that SAP +
NPC transplantation significantly improved locomotor score p <0.03) and enhanced
survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also
improved nerve conduction velocity (p = 0.008) but did not affect cavitation
volume (p = 0.73). CONCLUSION: Combinatorial NPC and SAP injection into injured
nerve tissue may enhance neural repair and regeneration.
PMID- 24351044
TI - Zebrafish heart failure models for the evaluation of chemical probes and drugs.
AB - Heart failure is a complex disease that involves genetic, environmental, and
physiological factors. As a result, current medication and treatment for heart
failure produces limited efficacy, and better medication is in demand. Although
mammalian models exist, simple and low-cost models will be more beneficial for
drug discovery and mechanistic studies of heart failure. We previously reported
that aristolochic acid (AA) caused cardiac defects in zebrafish embryos that
resemble heart failure. Here, we showed that cardiac troponin T and atrial
natriuretic peptide were expressed at significantly higher levels in AA-treated
embryos, presumably due to cardiac hypertrophy. In addition, several human heart
failure drugs could moderately attenuate the AA-induced heart failure by 10%-40%,
further verifying the model for drug discovery. We then developed a drug
screening assay using the AA-treated zebrafish embryos and identified three
compounds. Mitogen-activated protein kinase kinase inhibitor (MEK-I), an
inhibitor for the MEK-1/2 known to be involved in cardiac hypertrophy and heart
failure, showed nearly 60% heart failure attenuation. C25, a chalcone derivative,
and A11, a phenolic compound, showed around 80% and 90% attenuation,
respectively. Time course experiments revealed that, to obtain 50% efficacy,
these compounds were required within different hours of AA treatment.
Furthermore, quantitative polymerase chain reaction showed that C25, not MEK-I or
A11, strongly suppressed inflammation. Finally, C25 and MEK-I, but not A11, could
also rescue the doxorubicin-induced heart failure in zebrafish embryos. In
summary, we have established two tractable heart failure models for drug
discovery and three potential drugs have been identified that seem to attenuate
heart failure by different mechanisms.
PMID- 24351043
TI - Development of a QPatch automated electrophysiology assay for identifying KCa3.1
inhibitors and activators.
AB - The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1 (also known as
KCNN4, IK1, or the Gardos channel) plays an important role in the activation of T
and B cells, mast cells, macrophages, and microglia by regulating membrane
potential, cellular volume, and calcium signaling. KCa3.1 is further involved in
the proliferation of dedifferentiated vascular smooth muscle cells and fibroblast
and endothelium-derived hyperpolarization responses in the vascular endothelium.
Accordingly, KCa3.1 inhibitors are therapeutically interesting as
immunosuppressants and for the treatment of a wide range of fibroproliferative
disorders, whereas KCa3.1 activators constitute a potential new class of
endothelial function preserving antihypertensives. Here, we report the
development of QPatch assays for both KCa3.1 inhibitors and activators. During
assay optimization, the Ca(2+) sensitivity of KCa3.1 was studied using varying
intracellular Ca(2+) concentrations. A free Ca(2+) concentration of 1 MUM was
chosen to optimally test inhibitors. To identify activators, which generally act
as positive gating modulators, a lower Ca(2+) concentration (~200 nM) was used.
The QPatch results were benchmarked against manual patch-clamp electrophysiology
by determining the potency of several commonly used KCa3.1 inhibitors (TRAM-34,
NS6180, ChTX) and activators (EBIO, riluzole, SKA-31). Collectively, our results
demonstrate that the QPatch provides a comparable but much faster approach to
study compound interactions with KCa3.1 channels in a robust and reliable assay.
PMID- 24351046
TI - Implementation of an advanced occupational therapy assistant-led groups programme
in aged care rehabilitation.
AB - BACKGROUND/AIM: The use of support workers such as occupational therapy
assistants is emerging as a strategy to enhance the health workforce, but there
has been little evaluation of the feasibility of expanding support worker roles
and responsibilities. This study aimed to implement an advanced occupational
therapy assistant-led groups programme in a subacute aged care rehabilitation
setting and to evaluate the impact on the clinical outcomes of group
participants. METHOD: A prospective quasi-experimental cohort study was conducted
comparing outcomes of 30 patients receiving a groups programme led by an advanced
occupational therapy assistant with a historical control group of 40 patients
receiving the groups programme led by an occupational therapist. The groups
programme comprised up to six groups per week and included meal preparation
groups and domestic training groups. Outcomes were Functional Independence
Measure scores, Australian Therapy Outcome Measures, discharge destination,
length of stay and patient satisfaction. RESULTS: Discharge outcomes of patients
participating in the assistant-led groups programme were not significantly
different to patients who participated in the therapist-led groups programme.
Patient satisfaction levels were not significantly different between groups.
CONCLUSION: The introduction of an advanced occupational therapy assistant to
replace an occupational therapist in facilitating a groups programme in aged care
rehabilitation did not result in a decline in patient outcomes. However, the
results should be interpreted tentatively given the study limitations and the
advanced skills of the assistant involved. Further more rigorous longer term
research with a larger sample is required.
PMID- 24351045
TI - Structural and functional characterization of NanU, a novel high-affinity sialic
acid-inducible binding protein of oral and gut-dwelling Bacteroidetes species.
AB - Many human-dwelling bacteria acquire sialic acid for growth or surface display.
We identified previously a sialic acid utilization operon in Tannerella forsythia
that includes a novel outer membrane sialic acid-transport system (NanOU), where
NanO (neuraminate outer membrane permease) is a putative TonB-dependent receptor
and NanU (extracellular neuraminate uptake protein) is a predicted SusD family
protein. Using heterologous complementation of nanOU genes into an Escherichia
coli strain devoid of outer membrane sialic acid permeases, we show that the
nanOU system from the gut bacterium Bacteroides fragilis is functional and
demonstrate its dependence on TonB for function. We also show that nanU is
required for maximal function of the transport system and that it is expressed in
a sialic acid-responsive manner. We also show its cellular localization to the
outer membrane using fractionation and immunofluorescence experiments. Ligand
binding studies revealed high-affinity binding of sialic acid to NanU (Kd ~400
nM) from two Bacteroidetes species as well as binding of a range of sialic acid
analogues. Determination of the crystal structure of NanU revealed a monomeric
SusD-like structure containing a novel motif characterized by an extended kinked
helix that might determine sugar-binding specificity. The results of the present
study characterize the first bacterial extracellular sialic acid-binding protein
and define a sialic acid-specific PUL (polysaccharide utilization locus).
PMID- 24351047
TI - Emerging applications of proteomics in hip and knee arthroplasty.
AB - Total hip and knee arthroplasties are commonly performed orthopedic procedures
that involve a complex interaction between the prosthetic device and its
surrounding biological environment. Recent developments in the field of
proteomics have enabled a better understanding of these interactions in patients
with a total joint arthroplasty and have the potential to lead to development of
novel diagnostic and therapeutic modalities that may improve the care of these
patients, particularly those who have developed complications of wear,
osteolysis, loosening and periprosthetic joint infection. This article reviews
several of the areas of active research that are occurring at the intersection of
the fields of proteomics and total joint arthroplasty.
PMID- 24351048
TI - A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting
transforming growth factor-beta receptor II.
AB - BACKGROUND & AIMS: MicroRNAs (miRNAs) are a group of small non-coding RNAs with
modulator activity of gene expression. The role of miRNAs in hepatic ischaemia
reperfusion (IR) injury is currently largely unknown. The aim of this study was
to investigate the potential role of miR-370 in hepatic IR injury. METHODS: The
expression levels of hepatic miR-370 in male C57BL/6 mice subjected to hepatic IR
injury or ischaemia preconditioning were assessed by quantitative real-time PCR.
The effect of miR-370 on hepatic IR injury was investigated by serum enzyme
analysis and histological examination of liver following treatment of mice with
antagomir-370 or control. The levels of proinflammatory cytokines and apoptosis-
and proliferation-related genes were also determined by quantitative real-time
PCR. Furthermore, the potential targets of miR-370 in this injury were studied by
bioinformatics analysis, luciferase assays, quantitative real-time PCR and
Western blot. RESULTS: The results showed that miR-370 expression was
significantly upregulated in the mice subjected to hepatic IR injury as compared
with the sham-operated mice. Inhibition of miR-370 led to the downregulation of
serum aminotransferase and proinflammatory cytokines, as well as the improvement
of hepatic histological damage. Reporter assays confirmed that miR-370 directly
targeted the 3' untranslated region of transforming growth factor-beta receptor
II (TbetaRII). Inhibition of miR-370 was sufficient to reinstate the expression
of TbetaRII and its downstream target phosphorylated Smad3. CONCLUSION: Our data
suggest that miR-370 acting via TbetaRII might play a potential role in hepatic
IR injury, and inhibition of miR-370 efficiently attenuated the damage to the
liver.
PMID- 24351049
TI - Serum C-reactive protein as a diagnostic biomarker in dogs with bacterial
respiratory diseases.
AB - BACKGROUND: C-reactive protein (CRP) is a major acute-phase protein in dogs.
Serum concentrations are low in healthy animals, but increase rapidly after
inflammatory stimuli. OBJECTIVE: The aim of the study was to investigate CRP
concentrations in various respiratory diseases of dogs and to determine if CRP
can be used as a biomarker in the diagnosis of bacterial respiratory diseases.
ANIMALS: A total of 106 privately owned dogs with respiratory diseases (17 with
bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with
eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary
fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial
pneumonia [BP]) and 72 healthy controls. METHODS: The study was conducted as a
prospective cross-sectional observational study. CRP was measured in serum
samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic
imaging, and selected diagnostic methods such as cytological and microbiological
analysis of respiratory samples, echocardiography, and histopathology. RESULTS:
Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L;
interquartile range, 68-178 mg/L) than dogs with BTB (23, 15-38, P = .0003), CB
(13, 8-14, P < .0001), EBP (5, 5-15, P < .0001), CIPF (17, 10-20, P < .0001), or
CPE (19, 13-32, P < .0001) and healthy controls (14, 8-20, P < .0001). Dogs with
BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or
EBP (P < .0001) and healthy controls (P = .029). CONCLUSION AND CLINICAL
IMPORTANCE: These results indicate that CRP has potential for use as an
additional biomarker, especially in the diagnostics of BP.
PMID- 24351050
TI - Periodontal-ligament-derived stem cells exhibit the capacity for long-term
survival, self-renewal, and regeneration of multiple tissue types in vivo.
AB - Primary periodontal ligament stem cells (PDLSCs) are known to possess
multidifferentiation potential and exhibit an immunophenotype similar to that
described for bone-marrow-derived mesenchymal stem cells. In the present study,
bromo-deoxyuridine (BrdU)-labeled ovine PDLSCs implanted into immunodeficient
mice survived after 8 weeks post-transplantation and exhibited the capacity to
form bone/cementum-like mineralized tissue, ligament structures similar to
Sharpey's fibers with an associated vasculature. To evaluate self-renewal
potential, PDLSCs were recovered from harvested primary transplants 8 weeks post
transplantation that exhibit an immunophenotype and multipotential capacity
comparable to primary PDLSCs. The re-derived PDLSCs isolated from primary
transplants were implanted into secondary ectopic xenogeneic transplants.
Histomorphological analysis demonstrated that four out of six donor re-derived
PDLSC populations displayed a capacity to survive and form fibrous ligament
structures and mineralized tissues associated with vasculature in vivo, although
at diminished levels in comparison to primary PDLSCs. Further, the capacity for
long-term survival and the potential role of PDLSCs in dental tissue regeneration
were determined using an ovine preclinical periodontal defect model. Autologous
ex vivo-expanded PDLSCs that were prelabeled with BrdU were seeded onto
Gelfoam((r)) scaffolds and then transplanted into fenestration defects surgically
created in the periodontium of the second premolars. Histological assessment at 8
weeks post-implantation revealed surviving BrdU-positive PDLSCs associated with
regenerated periodontium-related tissues, including cementum and bone-like
structures. This is the first report to demonstrate the self-renewal capacity of
PDLSCs using serial xenogeneic transplants and provides evidence of the long-term
survival and tissue contribution of autologous PDLSCs in a preclinical
periodontal defect model.
PMID- 24351055
TI - Relative geographic range of sibling species of host damselflies does not
reliably predict differential parasitism by water mites.
AB - BACKGROUND: One of the main challenges in evolutionary parasitology is to
determine the factors that explain variation among host species in parasitism. In
this study, we addressed whether host phylogeny or ecology was important in
determining host species use by water mites. Parasitism (prevalence and
intensity) by Arrenurus water mites was examined in relation to geographic
distribution of host damselflies from sibling species pairs. In addition, the
likelihood of putative mite species parasitizing both species of a host species
pair was explored. RESULTS: A total of 1162 damselflies were examined for water
mites across four sites in Southeastern Ontario. These damselflies represent ten
species (five closely related host species pairs) in the Coenagrionidae. Only two
of the five species pairs showed near significant or significant differences in
prevalence of infection by mites. In one of those species comparisons, it was the
less widespread host that had higher water mite prevalence and in the other
species comparison, the less widespread host species had lower water mite
prevalence. Only one of the five pairs showed a significant difference in
intensity of infection; intensity was higher in the species with a smaller
geographic distribution. Based on the COI barcode, there were nine water mite
clades (OTU) infecting these ten host species. Three Arrenurus OTUs may be host
monospecific, four OTUs were specific to a given host species pair, and two OTUs
infected at least three host species. Host species in each species pairs tend to
share at least one of the Arrenurus OTU. No striking differences in mite species
diversity were found among species in any species pair. Finally, the Arrenurus
examined in this study appear to be ecological specialists, restricted to a
particular type of habitat, parasitizing few to many of the host species present
in that site or habitat. CONCLUSIONS: Although differences in levels of
parasitism by water mites exist for some closely related hosts species, no such
differences were found between other related host species. Differences in
geographic range of related host species does not reliably explain differential
levels of parasitism by water mites.
PMID- 24351056
TI - Interfacial self-assembly driven formation of hierarchically structured
nanocrystals with photocatalytic activity.
AB - We report the synthesis of hierarchical structured nanocrystals through an
interfacial self-assembly driven microemulsion (MU-emulsion) process. An
optically active macrocyclic building block Sn (IV) meso-tetraphenylporphine
dichloride (tin porphyrin) is used to initiate noncovalent self-assembly confined
within MU-emulsion droplets. In-situ studies of dynamic light scattering, UV-vis
spectroscopy, and electron microscopy, as well as optical imaging of reaction
processes suggest an evaporation-induced nucleation and growth self-assembly
mechanism. The resulted nanocrystals exhibit uniform shapes and sizes from ten to
a hundred nanometers. Because of the spatial ordering of tin porphyrin, the
hierarchical nanocrystals exhibit collective optical properties resulting from
the coupling of molecular tin porphyrin and photocatalytic activities in the
reduction of platinum nanoparticles and networks and in photodegradation of
methyl orange (MO) pollutants.
PMID- 24351057
TI - Population size and time since island isolation determine genetic diversity loss
in insular frog populations.
AB - Understanding the factors that contribute to loss of genetic diversity in
fragmented populations is crucial for conservation measurements. Land-bridge
archipelagoes offer ideal model systems for identifying the long-term effects of
these factors on genetic variations in wild populations. In this study, we used
nine microsatellite markers to quantify genetic diversity and differentiation of
810 pond frogs (Pelophylax nigromaculatus) from 24 islands of the Zhoushan
Archipelago and three sites on nearby mainland China and estimated the effects of
the island area, population size, time since island isolation, distance to the
mainland and distance to the nearest larger island on reduced genetic diversity
of insular populations. The mainland populations displayed higher genetic
diversity than insular populations. Genetic differentiations and no obvious gene
flow were detected among the frog populations on the islands. Hierarchical
partitioning analysis showed that only time since island isolation (square-root
transformed) and population size (log-transformed) significantly contributed to
insular genetic diversity. These results suggest that decreased genetic diversity
and genetic differentiations among insular populations may have been caused by
random genetic drift following isolation by rising sea levels during the
Holocene. The results provide strong evidence for a relationship between retained
genetic diversity and population size and time since island isolation for pond
frogs on the islands, consistent with the prediction of the neutral theory for
finite populations. Our study highlights the importance of the size and estimated
isolation time of populations in understanding the mechanisms of genetic
diversity loss and differentiation in fragmented wild populations.
PMID- 24351058
TI - The evolution of phenotypic correlations and "developmental memory".
AB - Development introduces structured correlations among traits that may constrain or
bias the distribution of phenotypes produced. Moreover, when suitable heritable
variation exists, natural selection may alter such constraints and correlations,
affecting the phenotypic variation available to subsequent selection. However,
exactly how the distribution of phenotypes produced by complex developmental
systems can be shaped by past selective environments is poorly understood. Here
we investigate the evolution of a network of recurrent nonlinear ontogenetic
interactions, such as a gene regulation network, in various selective scenarios.
We find that evolved networks of this type can exhibit several phenomena that are
familiar in cognitive learning systems. These include formation of a distributed
associative memory that can "store" and "recall" multiple phenotypes that have
been selected in the past, recreate complete adult phenotypic patterns accurately
from partial or corrupted embryonic phenotypes, and "generalize" (by exploiting
evolved developmental modules) to produce new combinations of phenotypic
features. We show that these surprising behaviors follow from an equivalence
between the action of natural selection on phenotypic correlations and
associative learning, well-understood in the context of neural networks. This
helps to explain how development facilitates the evolution of high-fitness
phenotypes and how this ability changes over evolutionary time.
PMID- 24351059
TI - Investigation of heterogeneity in the association between interferon beta and
disability progression in multiple sclerosis: an observational study.
AB - BACKGROUND AND PURPOSE: It was recently reported that there was no significant
overall association between interferon beta exposure and disability progression
in relapsing-remitting multiple sclerosis (RRMS) patients in an observational
study from Canada. In the current study, the potential for heterogeneity in the
association between exposure to interferon beta and disability progression across
patients' baseline characteristics was investigated. METHODS: RRMS patients
treated with interferon beta (n = 868) and two cohorts of untreated patients (829
contemporary and 959 historical controls) were included. The main outcome was
time from interferon beta treatment eligibility (baseline) to a confirmed and
sustained Expanded Disability Status Scale (EDSS) score 6 using a multivariable
Cox model, with treatment as a time-varying predictor, testing interaction
effects for five pre-specified baseline characteristics: sex, age, disease
duration, EDSS and annualized relapse rate (ARR) based on the previous 2 years.
RESULTS: Significant heterogeneity was found in the association of interferon
beta exposure and disability progression only across ARR, and only when treated
patients were compared with historical controls (P = 0.005 at a Bonferroni
adjusted alpha of 0.01). For patients with ARR>1, treatment-exposed time was
associated with a hazard ratio of 0.38 (95%CI 0.20-0.75) for disability
progression compared with the unexposed time. CONCLUSIONS: RRMS patients with
more frequent relapses at baseline may be more likely to benefit from interferon
beta treatment with respect to long-term disability progression.
PMID- 24351051
TI - QSAR modeling: where have you been? Where are you going to?
AB - Quantitative structure-activity relationship modeling is one of the major
computational tools employed in medicinal chemistry. However, throughout its
entire history it has drawn both praise and criticism concerning its reliability,
limitations, successes, and failures. In this paper, we discuss (i) the
development and evolution of QSAR; (ii) the current trends, unsolved problems,
and pressing challenges; and (iii) several novel and emerging applications of
QSAR modeling. Throughout this discussion, we provide guidelines for QSAR
development, validation, and application, which are summarized in best practices
for building rigorously validated and externally predictive QSAR models. We hope
that this Perspective will help communications between computational and
experimental chemists toward collaborative development and use of QSAR models. We
also believe that the guidelines presented here will help journal editors and
reviewers apply more stringent scientific standards to manuscripts reporting new
QSAR studies, as well as encourage the use of high quality, validated QSARs for
regulatory decision making.
PMID- 24351061
TI - Direct imaging of Pt single atoms adsorbed on TiO2 (110) surfaces.
AB - Noble metal nanoparticles (e.g., gold and platinum) supported on TiO2 surfaces
are utilized in many technological applications such as heterogeneous catalysts.
To fully understand their enhanced catalytic activity, it is essential to unravel
the interfacial interaction between the metal atoms and TiO2 surfaces at the
level of atomic dimensions. However, it has been extremely difficult to directly
characterize the atomic-scale structures that result when individual metal atoms
are adsorbed on the TiO2 surfaces. Here, we show direct atomic-resolution images
of individual Pt atoms adsorbed on TiO2 (110) surfaces using aberration-corrected
scanning transmission electron microscopy. Subangstrom spatial resolution enables
us to identify five different Pt atom adsorption sites on the TiO2 (110) surface.
Combining this with systematic density functional theory calculations reveals
that the most favorable Pt adsorption sites are on vacancy sites of basal oxygen
atoms that are located in subsurface positions relative to the top surface
bridging oxygen atoms.
PMID- 24351060
TI - The selectivity of Vibrio cholerae H-NOX for gaseous ligands follows the "sliding
scale rule" hypothesis. Ligand interactions with both ferrous and ferric Vc H
NOX.
AB - Vc H-NOX (or VCA0720) is an H-NOX (heme-nitric oxide and oxygen binding) protein
from facultative aerobic bacterium Vibrio cholerae. It shares significant
sequence homology with soluble guanylyl cyclase (sGC), a NO sensor protein
commonly found in animals. Similar to sGC, Vc H-NOX binds strongly to NO and CO
with affinities of 0.27 nM and 0.77 MUM, respectively, but weakly to O2. When
positioned on a "sliding scale" plot [Tsai, A.-l., et al. (2012) Biochemistry 51,
172-186], the line connecting log K(D)(NO) and log K(D)(CO) of Vc H-NOX can
almost be superimposed with that of Ns H-NOX. Therefore, the measured affinities
and kinetic parameters of gaseous ligands to Vc H-NOX provide more evidence to
validate the "sliding scale rule" hypothesis. Like sGC, Vc H-NOX binds NO in
multiple steps, forming first a six-coordinate heme-NO complex at a rate of 1.1 *
10(9) M(-1) s(-1), and then converts to a five-coordinate heme-NO complex at a
rate that is also dependent on NO concentration. Although the formation of
oxyferrous Vc H-NOX cannot be detected at a normal atmospheric oxygen level,
ferrous Vc H-NOX is oxidized to the ferric form at a rate of 0.06 s(-1) when
mixed with O2. Ferric Vc H-NOX exists as a mixture of high- and low-spin states
and is influenced by binding to different ligands. Characterization of both
ferric and ferrous Vc H-NOX and their complexes with various ligands lays the
foundation for understanding the possible dual roles in gas and redox sensing of
Vc H-NOX.
PMID- 24351062
TI - Breaking the silence: breast cancer knowledge and beliefs among Somali Muslim
women in Seattle, Washington.
AB - We elicited the perspectives of Somali women in Seattle, Washington, about breast
cancer. We conducted a focus group of 14 Somali immigrant women at a community
center in Seattle, Washington. Participants reported barriers to seeking cancer
screening, including fear of pain, difficulty with transport, and lack of
knowledge. Participants explained that Somali women tended not to discuss breast
cancer or breast cancer screening, and said religion played a central role in
their care and treatment decisions and coping mechanisms. If such barriers are
addressed, fewer women may present with late-stage breast cancer, resulting in
greater chances for long-term breast cancer survival.
PMID- 24351063
TI - Meeting the challenges of recruitment to multicentre, community-based, lifestyle
change trials: a case study of the BeWEL trial.
AB - BACKGROUND: Recruiting participants to multicentre, community-based trials is a
challenge. This case study describes how this challenge was met for the BeWEL
trial, which evaluated the impact of a diet and physical activity intervention on
body weight in people who had had pre-cancerous bowel polyps. METHODS: The BeWEL
trial was a community-based trial, involving centres linked to the Scottish
National Health Service (NHS) colorectal cancer screening programme. BeWEL had a
recruitment target of 316 and its primary recruitment route was the colonoscopy
clinics of the Scottish Bowel Screening Programme. RESULTS: BeWEL exceeded its
recruitment target but needed a 6-month no-cost extension from the funder to
achieve this. The major causes of delay were lower consent rates (49% as opposed
to 70% estimated from earlier work), the time taken for NHS research and
development department approvals and the inclusion of two additional sites to
increase recruitment, for which there were substantial bureaucratic delays. A
range of specific interventions to increase recruitment, for example, telephone
reminders and a shorter participant information leaflet, helped to increase the
proportion of eligible individuals consenting and being randomized. CONCLUSIONS:
Recruitment to multicentre trials is a challenge but can be successfully achieved
with a committed team. In a UK context, NHS research and development approval can
be a substantial source of delay. Investigators should be cautious when
estimating consent rates. If consent rates are less than expected, qualitative
analysis might be beneficial, to try and identify the reason. Finally,
investigators should select trial sites on the basis of a formal assessment of a
site's past performance and the likelihood of success in the trial being planned.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN53033856.
PMID- 24351064
TI - Warfarin monitoring economic evaluation of point of care self-monitoring compared
to clinic settings.
AB - OBJECTIVE: To determine the cost-effectiveness of home-based point-of-care self
monitoring compared to clinic-based care for patients managed on long-term
warfarin medication. Current evidence is inconsistent; results should reduce
uncertainty and inform service delivery. METHODS: A Markov model compared self
testing and self-management, using point-of-care devices to usual care in
patients with atrial fibrillation and mechanical heart valves. The primary
clinical end-points were stroke and mortality avoided; costs and utilities were
associated with these events. The costs of warfarin monitoring were included in
the model. RESULTS: Over 10 years, self-monitoring saved L1187 per person
compared to usual care. Patients who self-monitored had notably fewer strokes and
deaths. The results were sensitive to life-years gained and cost of the device.
If the NHS purchased the device, financial break-even was achieved at the end of
the second year; if the patient bought the device the NHS saved money every year.
If 10% of the current 950,000 patients switched to point-of-care devices for 10
years, the NHS could save over L112million. LIMITATIONS: Clinical studies had a
relatively short duration and only data on composite end-points were reported.
CONCLUSIONS: With training, self-testing and self-management are safe, reliable,
and cost-effective for a sizable proportion of patients receiving long-term
warfarin. Compared to clinic-based services, self-monitoring offers the NHS the
potential to make cost savings and release bed-days by reducing the number of
strokes experienced by these high-risk patients.
PMID- 24351065
TI - Histone decacetylase inhibitors prevent mitochondrial fragmentation and elicit
early neuroprotection against MPP+.
AB - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease,
characterized by progressive loss of dopaminergic (DA) neurons in the substantia
nigra. Recent investigations have shown that mitochondrial fragmentation, an
early event during apoptosis, is implicated in the degeneration of DA neurons in
PD, and more importantly, preventing mitochondrial fragmentation could rescue
cell death in several PD models. Therefore, mitochondrial dynamics may be a
therapeutic target for early intervention in PD. However, much remains unknown
about the mechanism underlying mitochondrial fragmentation in PD. METHODS: The
alterations in mitochondrial morphology, cell apoptosis, and mitochondrial
shaping protein levels were detected after SH-SY5Y cells were treated with
various doses of MPP+ or rotenone. RESULTS: Mitochondrial fragmentation is an
early event during apoptosis caused by MPP+ but not rotenone, and Trichostatin A
(TSA), a commonly used histone deacetylase (HDAC) inhibitor, selectively rescues
mitochondrial fragmentation and cell death induced by lower doses of MPP+.
Mitochondrial fragmentation triggered by lower doses of MPP+ may be a result of
Mfn2 down-regulation, which could be completely reversed by TSA. Further
investigation suggests that TSA prevents MPP+-induced Mfn2 down-regulation via
inhibiting histone deacetylation over Mfn2 promoter and alleviating its
transcriptional dysfunction. CONCLUSIONS: Histone deacetylase inhibitors prevent
mitochondrial fragmentation and elicit early neuroprotection in PD cell model
induced by MPP+. Hence, HDAC inhibitors may be a potential early treatment for
PD.
PMID- 24351066
TI - Peanut allergen in house dust of eating area and bed--a risk factor for peanut
sensitization?
AB - It has been hypothesized that high environmental exposure to peanut allergens may
be a potent risk factor for cutaneous sensitization. Therefore, we wanted to
investigate whether peanut proteins are detectable in house dust of different
household areas. Peanut levels of dust samples were measured with ELISA. Overall,
peanut was detectable in 19 of 21 households in the eating area and/or in bed.
The frequency of peanut consumption correlated with peanut levels. Forty-eight
hours after intentional peanut consumption, peanut levels were highly increased.
Nevertheless, further research is required to prove whether peanut allergen in
house dust can cause sensitization via skin.
PMID- 24351067
TI - Externalizing and internalizing behavioural problems related to asthma in school
children.
AB - We investigated the relationships of behavioural problems as assessed using the
standardized Strengths and Difficulties Questionnaire (SDQ) to asthma in view of
improving asthma management. Six thousand eight hundred and eighty children (mean
age 10.4 years, male: 49%) were recruited in the French 6 Cities Study. Children
with abnormal or borderline emotional symptoms (internalizing problems) or
conduct problems (externalizing problems) were more asthmatic than others (P <
0.01). Compared to being normal, abnormal emotional symptoms or conduct problems
were found to be related to mild-to-moderate persistent asthma (logistic model
adjusted odds ratio = 1.55 (95% CI = 1.26-1.90) and 1.42 (95% CI = 1.17-1.71),
respectively) and to early-onset asthma (Cox's model Adjusted Hazard Risk = 1.60
(95% CI = 1.27-2.01) and 1.34 (95% CI = 1.05-1.70). Borderline conduct problems
were found to be negatively related to parents' knowledge on how to prevent
asthma attacks, compared to normal conduct problems [adjusted OR = 0.51 (95% CI =
0.31-0.85)]. Further data are needed to better understand the involvement of
behavioural problems in childhood asthma according to phenotypes.
PMID- 24351068
TI - Birch pollen sensitization with cross-reactivity to food allergens predominates
in adults with eosinophilic esophagitis.
AB - EoE patients show variable sensitization patterns to food and aeroallergens. The
value of allergy testing in adult EoE patients is unclear. Component-resolved
diagnosis (CRD) may offer additional insights into sensitization patterns. The
aim of this study was to characterize sensitization patterns in adult EoE
patients using CRD. Serum from 76 patients (17 female), age 38.6 +/- 1.5 years,
was analyzed for reactivity to 112 different allergen components using an immuno
solid-phase allergen chip (ISAC). We observed any sensitization in 59 patients
(78%), of which 54 patients were polysensitized. Aeroallergen sensitization,
mostly against components of grass or tree pollen, or house dust mite, was
observed in 74% of the patients. Birch pollen (rBet v 1) sensitization with cross
reactivity to food allergen components was observed in 30 patients (39%). In
conclusion, food sensitizations in EoE patients are mainly caused by cross
reactivity to food allergens after primary birch pollen sensitization. Pollen and
food sensitizations may cause or maintain esophageal inflammation in EoE
patients. CRD provides more insight into sensitization patterns, identifies
additional food allergen sensitizations and might be useful to direct dietary
therapy in EoE.
PMID- 24351069
TI - Rapid desensitization to chemotherapy and monoclonal antibodies is effective and
safe.
PMID- 24351070
TI - Diversity of allergens contained in dog saliva.
PMID- 24351071
TI - A novel modified ultra-long agonist protocol improves the outcome of high body
mass index women with polycystic ovary syndrome undergoing IVF/ICSI.
AB - In an attempt to evaluate the effectiveness of a novel modified ultra-long
agonist (ULA) protocol on polycystic ovary syndrome (PCOS) patients undergoing in
vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI), a
retrospective study of 499 women employed with either ULA or conventional long
agonist (LA) protocol was analyzed. In high BMI group (>25 kg/m2), the ULA
protocol yielded significant higher clinic pregnancy rate (PR) (70.2% versus
50.8%, p < 0.05), implantation rate (52.7% versus 35.7%, p < 0.05) and live birth
rate (63.8% versus 39.0%, p < 0.05) when compared with LA protocol. In low BMI
group (<=25 kg/m2), the ULA protocol also demonstrated a higher clinic PR (70.8%
versus 59.5%, p < 0.05) whereas implantation rate and live birth rate are
comparable. Within ULA protocol, the clinic PR, implantation rate and live birth
rate are similar between high and low BMI patients. Similarly, the clinic PR and
live birth rate demonstrated no significant difference within LA group but there
is a significant lower implantation rate (35.7% versus 63.9%, p < 0.05) observed
in high BMI patients. No difference in miscarriage rate and severe OHSS rate was
found among all groups. In conclusion, ULA protocol benefits the IVF outcomes of
PCOS patients with high BMI status.
PMID- 24351072
TI - Comparison between effects of myo-inositol and D-chiro-inositol on ovarian
function and metabolic factors in women with PCOS.
AB - Myo-inositol and D-chiro-inositol are capable of improving the ovarian function
and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work
is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We
enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS
and menstrual irregularities, and we randomly divided them into two groups: 25
were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally
for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic
acid/die orally for six months. We analyzed in both groups pre-treatment and post
treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score,
Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone,
dehydroepiandrosterone sulfate (DHEA-S), Delta-4-androstenedione, SHBG,
prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model
assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the
isoforms of inositol were effective in improving ovarian function and metabolism
in patients with PCOS, although myo-inositol showed the most marked effect on the
metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.
PMID- 24351073
TI - Higher levels of circulating CXCL-9 and CXCL-11 in euthyroid women with
autoimmune thyroiditis and recurrent spontaneous abortions.
AB - BACKGROUND: We aimed to measure serum CXCL-9 and CXCL-11 levels in patients with
autoimmune thyroiditis (AIT) and recurrent spontaneous abortions (RSA). METHODS:
Forty-one euthyroid, non-pregnant women with AIT and a history of unexplained
first trimester RSA, 35 euthyroid women with AIT, and 29 healthy controls matched
for age and body mass index were enrolled. Serum CXCL-9 and CXCL-11 were
measured. RESULTS: Serum CXCL-9 and -11 levels were significantly higher (p <
0.001 for both) in the antibody-positive women with a history of abortions than
in both control groups. Additionally, CXCL-9 levels were higher in patients with
AIT without RSA than in healthy controls. No significant differences were found
in CXCL-9 and -11 levels in subjects with a history of RSA in relation to the
number of previous abortions. In multiple linear regression analyses, abortions
were significantly related to CXCL-9 (beta-coefficient = 0.174, p < 0.001), CXCL
11 (beta-coefficient = 0.490, p < 0.001). CONCLUSION: Higher circulating levels
of CXCL-9 and -11 have been shown in non-pregnant AIT patients with a history of
RSA as compared to both control groups, suggesting that this subgroup produce a
more dominant Th-1 cytokine profile.
PMID- 24351074
TI - Zwitterionic-based stainless steel with well-defined polysulfobetaine brushes for
general bioadhesive control.
AB - Stainless steels are widely used as orthopaedic and dental implant; however,
bioadhesion in the case of thrombosis, inflammation, and infection is one of
their major limitations. One way to tackle this problem is to graft the stainless
steel surface with a zwitterionic polymer known for being anti-bioadhesive.
Controlled atom transfer radical polymerization (ATRP) of zwitterionic
poly(sulfobetaine methacrylate) (polySBMA) grafted from biomedical grade
stainless steel surface was employed in this study. The interactions of polySBMA
grafted surfaces with biomacromolecules were demonstrated in vitro by the
adhesion tests of plasma protein, blood cells, human MG63 osteoblast- and HT1080
fibroblast-like cells in biological complex media to evaluate their bioadhesive
properties. Anti-microbial effects were also assessed for two most ordinary seen
clinical bacteria, i.e., Escherichia coli and Staphylococcus epidermidis. Results
showed that polySBMA-grafted surface exhibited evident bioadhesion resistance and
conferring antibacterial efficacy. This work is also dedicated to deduce the
effectiveness of polySBMA brushes' conformational structure on the prevention of
bioadhesion. To this aim, the anti-bioadhesive effect of polySBMA brushes
prepared by dopamine- and silane-surfaced immobilization method was evaluated.
Results show that polySBMA grafted from immobilized polydopamine interfacial
layers achieved better bioadhesion resistance, which could be causally related to
their greater grafting coverage, flexible brush conformational structures, and
greater hydration capabilities.
PMID- 24351075
TI - Iron biofortification of rice using different transgenic approaches.
AB - More than 2 billion people suffer from iron (Fe) deficiency, and developing crop
cultivars with an increased concentration of micronutrients (biofortification)
can address this problem. In this review, we describe seven transgenic
approaches, and combinations thereof, that can be used to increase the
concentration of Fe in rice seeds. The first approach is to enhance the Fe
storage capacity of grains through expression of the Fe storage protein ferritin
under the control of endosperm-specific promoters. Using this approach, the
concentration of Fe in the seeds of transformants was increased by approximately
2-fold in polished seeds. The second approach is to enhance Fe translocation by
overproducing the natural metal chelator nicotianamine; using this approach, the
Fe concentration was increased by up to 3-fold in polished seeds. The third
approach is to enhance Fe influx to the endosperm by expressing the Fe(II)
nicotianamine transporter gene OsYSL2 under the control of an endosperm-specific
promoter and sucrose transporter promoter, which increased the Fe concentration
by up to 4-fold in polished seeds. The fourth approach is introduction of the
barley mugineic acid synthesis gene IDS3 to enhance Fe uptake and translocation
within plants, which resulted in a 1.4-fold increase in the Fe concentration in
polished seeds during field cultivation. In addition to the above approaches, Fe
biofortified rice was produced using a combination of the first, second, and
third approaches. The Fe concentration in greenhouse-grown T2 polished seeds was
6-fold higher and that in paddy field-grown T3 polished seeds was 4.4-fold higher
than in non-transgenic seeds without any reduction in yield. When the first and
fourth approaches were combined, the Fe concentration was greater than that
achieved by introducing only the ferritin gene, and Fe-deficiency tolerance was
observed. With respect to Fe biofortification, the introduction of multiple Fe
homeostasis genes is more effective than the introduction of individual genes.
Moreover, three additional approaches, i.e., overexpression of the Fe transporter
gene OsIRT1 or OsYSL15, overexpression of the Fe deficiency-inducible bHLH
transcription factor OsIRO2, and knockdown of the vacuolar Fe transporter gene
OsVIT1 or OsVIT2, may be useful to further increase the Fe concentration of
seeds.
PMID- 24351076
TI - Models for intensive care training. A European perspective.
AB - The diversity of European culture is reflected in its healthcare training
programs. In intensive care medicine (ICM), the differences in national training
programs were so marked that it was unlikely that they could produce specialists
of equivalent skills. The Competency-Based Training in Intensive Care Medicine in
Europe (CoBaTrICE) program was established in 2003 as a Europe-based worldwide
collaboration of national training organizations to create core competencies for
ICM using consensus methodologies to establish common ground. The group's
professional and research ethos created a social identity that facilitated
change. The program was easily adaptable to different training structures and
incorporated the voice of patients and relatives. The CoBaTrICE program has now
been adopted by 15 European countries, with another 12 countries planning to
adopt the training program, and is currently available in nine languages,
including English. ICM is now recognized as a primary specialty in Spain,
Switzerland, and the UK. There are still wide variations in structures and
processes of training in ICM across Europe, although there has been agreement on
a set of common program standards. The combination of a common "product
specification" for an intensivist, combined with persisting variation in the
educational context in which competencies are delivered, provides a rich source
of research inquiry. Pedagogic research in ICM could usefully focus on the
interplay between educational interventions, healthcare systems and delivery, and
patient outcomes, such as including whether competency-based program are
associated with lower error rates, whether communication skills training is
associated with greater patient and family satisfaction, how multisource feedback
might best be used to improve reflective learning and teamworking, or whether
increasing the proportion of specialists trained in acute care in the hospital at
weekends results in better patient outcomes.
PMID- 24351077
TI - Novel evidence for the specific interaction between cholesterol and alpha
haemolysin of Escherichia coli.
AB - Several toxins that act on animal cells present different, but specific,
interactions with cholesterol or sphingomyelin. In the present study we
demonstrate that HlyA (alpha-haemolysin) of Escherichia coli interacts directly
with cholesterol. We have recently reported that HlyA became associated with
detergent-resistant membranes enriched in cholesterol and sphingomyelin;
moreover, toxin oligomerization, and hence haemolytic activity, diminishes in
cholesterol-depleted erythrocytes. Considering these results, we studied the
insertion process, an essential step in the lytic mechanism, by the monolayer
technique, finding that HlyA insertion is favoured in cholesterol- and
sphingomyelin-containing membranes. On the basis of this result, we studied the
direct interaction with either of the lipids by lipid dot blotting, lysis
inhibition and SPR (surface plasmon resonance) assays. The results of the present
study demonstrated that an interaction between cholesterol and HlyA exists that
seems to favour a conformational state of the protein that allows its correct
insertion into the membrane and its further oligomerization to form pores.
PMID- 24351078
TI - The impact of early cytomegalovirus infection after kidney transplantation on
long-term graft and patient survival.
AB - This prospective observational cohort study is an extension of a previous study
reporting effects of cytomegalovirus (CMV) on graft and patient survival in 471
patients who underwent kidney transplantation between 1994 and 1997. CMV pp65
antigen was measured every 7-14 d during the first three months after
transplantation, given as number of CMV pp65-positive cells per 10(5) leukocytes.
A positive test was defined as CMV infection. None of the patients received CMV
prophylaxis or preemptive treatment. During a median of 13.7 (7.1-14.9) yr, the
number of death-censored graft losses was 118 (25%) and of patient deaths 224
(48%). CMV infection was an independent significant risk factor for mortality in
multivariate analysis (HR = 1.453, 95% CI 1.033-2.045, p = 0.032), adjusting for
patient and donor age, preemptive transplantation, HLA-DR and -AB mismatches,
living donor, acute rejection during the first three months, donor-recipient CMV
IgG antibody status and diabetic nephropathy. In univariate analysis, CMV
infection was significantly associated with death-censored graft loss but the
association was not significant in multivariate model. CMV infection early after
kidney transplantation is a predictor of overall mortality but not of death
censored graft loss after a median observation period of 13.7 yr.
PMID- 24351079
TI - A randomized, double-blind, placebo-controlled study of the efficacy and safety
of MNK-795, a dual-layer, biphasic, immediate-release and extended-release
combination analgesic for acute pain.
AB - OBJECTIVE: To investigate the efficacy and safety of a bilayer combination
oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and
extended-release (ER) components (OC/APAP ER) in patients with moderate to severe
pain using an established acute pain model. RESEARCH DESIGN AND METHODS: This was
a randomized, double-blind, placebo-controlled trial. Adult patients were
included in the study if they had a pain intensity score>=4 on a 0-10 numerical
rating scale after bunionectomy surgery, and were randomized (1:1) to receive
four doses (two tablets q12h) of OC/APAP ER or placebo. CLINICAL TRIAL
REGISTRATION: NCT01484652. MAIN OUTCOME MEASURES: The primary efficacy endpoint
was the summed pain intensity difference over the first 48 hours (SPID48).
Secondary endpoints included SPIDs and total pain relief (TOTPAR) over the dosing
intervals; time to perceptible, meaningful, and confirmed pain relief; and the
proportion of patients with >=30% reduction in pain intensity scores. RESULTS: A
total of 329 patients were enrolled, of whom 266 (OC/APAP ER, n=135; placebo,
n=131) completed the study. The mean (SE) SPID48 was 114.9 (7.6) in the OC/APAP
ER group and 66.9 (7.6) in the placebo group (P<0.0001). SPID and TOTPAR values
were significantly greater with OC/APAP ER than with placebo over all time
periods analyzed, and the median times to perceptible, meaningful, and confirmed
pain relief were significantly shorter. More patients showed >=30% reduction in
pain intensity scores with OC/APAP ER than with placebo at all times after 0.5
hours. OC/APAP ER was generally well tolerated. A limitation of this study was
the lack of an active comparator. CONCLUSIONS: OC/APAP ER was efficacious and
generally well tolerated in an established model of moderate to severe acute
pain, providing an onset of analgesia in approximately 30 minutes and sustained
pain relief over the 12 hour dosing period.
PMID- 24351080
TI - Expression of toll-like receptors 1-5 but not TLR 6-10 is elevated in livers of
patients with non-alcoholic fatty liver disease.
AB - BACKGROUND & AIMS: Animal models of non-alcoholic fatty liver disease (NAFLD)
suggest that an increased translocation of bacterial endotoxins, leading to an
activation of toll-like receptor-dependent signalling cascades (TLRs) and
increased formation of reactive oxygen species, may add to development of insulin
resistance and induction of plasminogen activator inhibitor-1 (PAI-1) in the
liver. If similar mechanisms are also involved in the development of NAFLD in
humans remains to be determined. METHODS: Toll-like receptor (1-10), myeloid
differentiation primary response gene (MyD88), interferon regulatory
transcription factor 3 (IRF-3) and insulin receptor substrate 1 (IRS-1) mRNA
expression was determined in liver samples of 11 patients with NAFLD and 11
controls. Hepatic PA1-1 and 4-hydroxynonenal protein adducts (4-HNE) levels were
determined by immunohistochemistry. RESULTS: Hepatic TLR 1-5 mRNAs expression was
significantly higher in livers of NAFLD patients than in controls, whereas
expression of TLR 6-10 mRNAs did not differ between groups. Expression of MyD88
but not IRF-3 was also significantly higher in livers of NAFLD patients than in
controls. These alterations were associated with significantly higher levels of 4
HNE and PAI-1 protein levels in livers of NAFLD patients than in controls,
whereas IRS-1 mRNA expression was ~80% lower in livers of NAFLD patients than in
controls. CONCLUSIONS: Taken together, these findings add further weight to the
hypothesis that alterations at the level of intestine and intestinal barrier
function may be critical in the development of NAFLD in humans.
PMID- 24351081
TI - Acute and chronic stress increase salivary cortisol: a study in the real-life
setting of a national examination undertaken by medical graduates.
AB - Spanish medical graduates who apply for a medical specialty training position
(MIR) must take an examination that will shape their future personal and
professional lives. Preparation for the test represents an important stressor
that persists for several months. The aim of this study was to elucidate the
stress pattern of this group and evaluate possible changes in the circadian
rhythm of cortisol release in medical graduates preparing for this test. A
repeated-measures longitudinal study was performed, measuring the salivary
cortisol concentrations in 36 medical graduates (13 males and 23 females; mean
age of 24.2 years) on five sampling days. Five cortisol samples were collected
from 07:00 to 21:00 h in order to monitor changes in the circadian rhythm. On all
sampling days (except on the day of the official examination), anxiety and
psychological stress were evaluated with the Spanish versions of the State-Trait
Anxiety Inventory (STAI) and the Perceived Stress Scale (PSS). During the study
period, participants showed higher levels of anxiety than the Spanish reference
population as well as a progressive increase in self-perceived stress. A
significant increase in salivary cortisol concentration was observed in both
chronic (study and examination preparation) and acute (examinations) situations.
Our results suggest that the cortisol awakening response (CAR) may be a good
indicator of anticipatory stress but is unaffected by long-term examination
preparation. Comparison of results between the official examination day and the
mock examination days yielded evidence that learning may modulate the behavior of
the hypothalamic-pituitary-adrenal axis.
PMID- 24351082
TI - Spectroimmunohistochemistry: a novel form of MALDI mass spectrometry imaging
coupled to immunohistochemistry for tracking antibodies.
AB - MALDI mass spectrometry imaging (MALDI-MSI) is currently used for clinical
applications, such as biomarker identification, particularly for the study of
solid tumors. The ability to map specific compounds that have been determined to
be biomarkers and therapeutic targets is relevant for the evaluation of the
efficacy of targeted therapies. This article describes a new method called
Spectro-ImmunoHistoChemistry (SIHC), which combines the use of specific
antibodies against markers and mass spectrometric imaging in the MS/MS mode. SIHC
is based on direct primary antibody-antigen recognition, trypsin digestion of the
antibody overlaying the markers of interest in the tissue section, and MALDI-MSI
of the tryptic peptides generated from the antibody. This approach has both
clinical and pharmacological applications. First, it can be used as a cross
validation method to monitor the presence specifically of a marker in a tissue
section. Second, SIHC could potentially be used as a novel technology for
tracking specific antibodies after in vivo injection for anti-cancer treatments.
Additionally, SIHC could enable novel clinical applications of MSI, such as
monitoring the efficacy of cytotoxic antibody treatments.
PMID- 24351083
TI - Chemical characterization and source apportionment of household fine particulate
matter in rural, peri-urban, and urban West Africa.
AB - Household air pollution in sub-Saharan Africa and other developing regions is an
important cause of disease burden. Little is known about the chemical composition
and sources of household air pollution in sub-Saharan Africa, and how they differ
between rural and urban homes. We analyzed the chemical composition and sources
of fine particles (PM2.5) in household cooking areas of multiple neighborhoods in
Accra, Ghana, and in peri-urban (Banjul) and rural (Basse) areas in The Gambia.
In Accra, biomass burning accounted for 39-62% of total PM2.5 mass in the cooking
area in different neighborhoods; the absolute contributions were 10-45 MUg/m(3).
Road dust and vehicle emissions comprised 12-33% of PM2.5 mass. Solid waste
burning was also a significant contributor to household PM2.5 in a low-income
neighborhood but not for those living in better-off areas. In Banjul and Basse,
biomass burning was the single dominant source of cooking-area PM2.5, accounting
for 74-87% of its total mass; the relative and absolute contributions of biomass
smoke to PM2.5 mass were larger in households that used firewood than in those
using charcoal, reaching as high as 463 MUg/m(3) in Basse homes that used
firewood for cooking. Our findings demonstrate the need for policies that enhance
access to cleaner fuels in both rural and urban areas, and for controlling
traffic emissions in cities in sub-Saharan Africa.
PMID- 24351084
TI - Casting doubt on the traditional approach of cancer biomarker discovery through
proteomics.
AB - Towards revolutionary biomarkers, a considerable amount of research funds and
time have been dedicated to proteomics. Although the discovery of novel
biomarkers at the dawn of proteomics was a promising development, only a few
identified biomarkers seemed to be beneficial for cancer patients. We may need to
approach this issue differently, instead of only extending the conventional
approaches that have been used historically. The study of biomarkers is
essentially a study of diseases and the biochemistry relating to peptide, protein
and post-translational modifications is only a tool. A problem-oriented approach
should be needed in biomarker development. Clinician participation in the study
of biomarkers will lead to realistic, practical and interesting biomarker
candidates, which justify the time and expense involved in validation studies.
Although discussion in this article is focused on cancer biomarkers, it can
generally be applied to biomarker studies for other diseases.
PMID- 24351085
TI - Interlocus sexually antagonistic coevolution can create indirect selection for
increased recombination.
AB - The ubiquity of recombination in nature is a paradox because it breaks up
combinations of alleles favored by natural selection. Theoretical work has shown
that antagonistic coevolution between hosts and parasites can result in rapid
fluctuations in epistasis that can create a short-term advantage to
recombination. Here, we show that another kind of antagonistic coevolution,
interlocus sexually antagonistic coevolution (SAC), can also create indirect
selection for modifiers that increase the rate of recombination, and that it can
lead to very high levels of recombination at equilibrium. Recombination is
favored because interlocus SAC creates heterogeneity in the strength and
direction of selection, both within and between generations, which maintains an
excess of disadvantageous haplotypes in the population. This result is similar to
and consistent with dynamics of fluctuating epistasis produced in models of host
parasite coevolution. However, the conditions under which interlocus SAC provides
an advantage to recombination are more permissive.
PMID- 24351086
TI - Hypoglycaemic events in patients with type 2 diabetes in the United Kingdom:
associations with patient-reported outcomes and self-reported HbA1c.
AB - BACKGROUND: One possible barrier to effective diabetes self-management is
hypoglycaemia associated with diabetes medication. The current study was
conducted to characterize hypoglycaemic events among UK patients with type 2
diabetes (T2D) treated with antihyperglycaemic medications, and assess the
relationship between experience of hypoglycaemic events and health outcomes,
including glycaemic control, health-related quality of life, impairment to work
and non-work activities, treatment satisfaction, adherence to treatment, fear of
hypoglycaemia, and healthcare resource use. METHODS: An online survey of 1,329
T2D patients in UK drawn from an opt-in survey panel was conducted in February of
2012 with monthly follow-up questionnaires for five months. Measures included
self-reported HbA1c, EQ-5D, Work Productivity and Activity Impairment
questionnaire, Diabetes Medication Satisfaction Tool, Morisky medication
adherence scale, the Hypoglycaemia Fear Survey (revised), and self-reported
healthcare resource use. Comparisons were conducted using t-tests and chi-square
tests for continuous and categorical variables, respectively. RESULTS: Baseline
comparisons showed that worse HbA1c, greater diabetes-related healthcare resource
use, greater fear of hypoglycaemia, and impaired health outcomes were associated
with experience of hypoglycaemia in the four weeks prior to baseline.
Longitudinal results were similar in direction but differences on few measures
were significant. CONCLUSIONS: In real-world UK T2D patients, hypoglycaemia is
associated with worse self-reported glycaemic control, behaviours that contribute
to worse glycaemic control, and impairment in patient-reported outcomes.
PMID- 24351087
TI - Outcome of fulminant bacterial meningitis in adult patients.
AB - BACKGROUND AND PURPOSE: The objective of our study was to identify neurological
factors associated with poor outcome in adult patients with fulminant bacterial
meningitis. METHODS: This was a retrospective review of consecutive adult
patients with fulminant bacterial meningitis, defined as meningitis causing coma
within 24-48 h of hospitalization, at Mayo Clinic Rochester between January 2000
and November 2010. Functional status was assessed at discharge and upon last
follow-up using the modified Rankin scale (mRS). The primary end-point was death
or new major disability (increase of >2 on the mRS) at last follow-up. RESULTS:
Thirty-nine patients were identified. Encephalopathy (44%), coma (28%), focal
seizures (3%) or a combination of these (26%) were present on admission. The most
common pathogen was Streptococcus pneumoniae (57%). All patients were treated
with broad spectrum antibiotics and 51% received steroids. Serious systemic
complications were seen in 23 patients. Sixteen patients (41%) died during
hospitalization. Median mRS at hospital discharge for surviving patients was 3;
four patients had new major disability with a mean follow-up of 11 months.
Predictors of death or new major disability included lower Glasgow Coma Scale
score at nadir [P = 0.002; age- and sex-adjusted odds ratio (OR) 0.46, 95%
confidence interval (CI) 0.28-0.48], longer duration of symptoms before
hospitalization (P = 0.045; adjusted OR 2.34, 95% CI 1.02-5.37), abnormal head
imaging at presentation (P = 0.008; adjusted OR 9.40, 95% CI 1.78-49.6) and use
of intracranial pressure monitoring (P = 0.010, adjusted OR 51.0, 95% CI 2.51
1036). CONCLUSION: Many adult patients who survive hospitalization are able to
regain their pre-morbid level of function. Aggressive management of bacterial
meningitis is justified even in comatose adult patients.
PMID- 24351089
TI - Perception of humanization of birth in a highly specialized hospital: let's think
differently.
AB - Our goal for this article was to identify the perceptions of health care
professionals, administrators, and women concerning the humanization of
childbirth care in a tertiary hospital. A single-case study design and a
qualitative approach were used. We collected data through semistructured
interviews, participant observation, field notes, and a questionnaire. The
humanization of birth in a tertiary hospital is identifiable by several key
characteristics such as personalization, recognition of women's rights, human
caring, women's advocacy and companionship, and a balance between medical care
and comfort, safety, and humanity.
PMID- 24351088
TI - Guided and unguided CBT for social anxiety disorder and/or panic disorder via the
Internet and a smartphone application: study protocol for a randomised controlled
trial.
AB - BACKGROUND: Smartphone technology presents a novel and promising opportunity to
extend the reach of psychotherapeutic interventions by moving selected parts of
the therapy into the real-life situations causing distress. This randomised
controlled trial will investigate the effects of a transdiagnostic, Internet
administered cognitive behavioural (iCBT) self-help program for anxiety,
supplemented with a smartphone application. The effect of added therapist support
will also be studied. METHODS/DESIGN: One hundred and fifty participants meeting
diagnostic criteria for social anxiety disorder and/or panic disorder will be
evenly randomised to either one of three study groups: 1, smartphone-supplemented
iCBT with therapist support; 2, smartphone-supplemented iCBT without therapist
support; or 3, an active waiting list control group with delayed treatment.
Primary outcome measure will be the Generalised Anxiety Disorder 7-item self
rating scale. Secondary measures include other anxiety, depression and quality of
life measures. In addition to pre- and post-treatment measurements, the study
includes two mid-treatment (days 24 and 48) and two follow-up assessments (12 and
36 months) to assess rapid and long-term effects. DISCUSSION: To our knowledge,
this is the first study to investigate the effectiveness of smartphone
supplemented iCBT for anxiety disorders. Hence, the findings from this trial will
constitute great advancements in the burgeoning and promising field of smartphone
administered psychological interventions. Limitations are discussed. TRIAL
REGISTRATION: Clinicaltrials.gov: NCT01963806.
PMID- 24351090
TI - DNA origami compliant nanostructures with tunable mechanical properties.
AB - DNA origami enables fabrication of precise nanostructures by programming the self
assembly of DNA. While this approach has been used to make a variety of complex
2D and 3D objects, the mechanical functionality of these structures is limited
due to their rigid nature. We explore the fabrication of deformable, or
compliant, objects to establish a framework for mechanically functional
nanostructures. This compliant design approach is used in macroscopic engineering
to make devices including sensors, actuators, and robots. We build compliant
nanostructures by utilizing the entropic elasticity of single-stranded DNA
(ssDNA) to locally bend bundles of double-stranded DNA into bent geometries whose
curvature and mechanical properties can be tuned by controlling the length of
ssDNA strands. We demonstrate an ability to achieve a wide range of geometries by
adjusting a few strands in the nanostructure design. We further developed a
mechanical model to predict both geometry and mechanical properties of our
compliant nanostructures that agrees well with experiments. Our results provide a
basis for the design of mechanically functional DNA origami devices and
materials.
PMID- 24351091
TI - Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir
in HIV-1 infected treatment-naive women of childbearing age.
AB - BACKGROUND: Guidelines from the Department of Health and Human Services in the US
recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor
(PI) for HIV-positive antiretroviral-naive pregnant women. These guidelines also
cite ritonavir-boosted darunavir (DRV + RTV) as an alternative PI in this
clinical scenario. The purpose of this analysis was to compare economic outcomes
for regimens based on these two treatments. STUDY DESIGN: An existing discrete
event simulation (DES) model was adapted to conduct a cost-minimization analysis
comparing the two regimens in HIV-infected women of childbearing age (WOCBA),
from the perspective of a healthcare payer in the US. METHODS: The DES model was
used to represent disease states, health events, healthcare encounters,
pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with
regimens based on either LPV/r or DRV + RTV. It also incorporated parameters for
individual patient characteristics, and for antiretroviral (ARV) treatment
effectiveness, treatment sequencing, clinical progression, and resource use.
Potential events included scheduled physician visits; viral suppression; viral
rebound; AIDS-related complications; CHD events; treatment discontinuation and
switching; ARV treatment side-effects (SE); and death. The primary outcomes were
discounted 5-year and 10-year healthcare costs. Alternative scenarios considered
different rates of switching from DRV + RTV to LPV/r upon conception. RESULTS:
Compared with DRV + RTV, LPV/r was associated with similar clinical outcomes
while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per
patient, respectively), and in extensive sensitivity analyses. The main driver of
the savings was the difference in cost between PIs. CONCLUSIONS: Starting HIV
infected ARV-treatment-naive WOCBA on an LPV/r-based regimen is cost-saving and
provides similar patient outcomes compared to a DRV + RTV-based regimen.
PMID- 24351092
TI - Total synthesis of heronapyrrole C.
AB - A flexible total synthesis of the 2-nitropyrrole-derived marine natural product,
(+)-heronapyrrole C, is reported. The approach is based on regioselective access
to key building blocks containing the rare 4-substituted 2-nitropyrrole motif.
Sharpless asymmetric epoxidation and dihydroxylation and a Shi epoxidation were
used to introduce the five stereogenic centers of the bis-THF-diol side chain.
The N-benzoyloxymethyl (Boz) protecting group was crucial for functionalization
of the 2-nitropyrrole moiety and enabling final deprotection under mild
conditions.
PMID- 24351093
TI - Electron transport limitation in P3HT:CdSe nanorods hybrid solar cells.
AB - Hybrid solar cells have the potential to be efficient solar-energy-harvesting
devices that can combine the benefits of solution-processable organic materials
and the extended absorption offered by inorganic materials. In this work, an
understanding of the factors limiting the performance of hybrid solar cells is
explored. Through photovoltaic-device characterization correlated with transient
absorption spectroscopy measurements, it was found that the interfacial charge
transfer between the organic (P3HT) and inorganic (CdSe nanorods) components is
not the factor limiting the performance of these solar cells. The insulating
original ligands retard the charge recombination between the charge-transfer
states across the CdSe-P3HT interface, and this is actually beneficial for charge
collection. These cells are, in fact, limited by the subsequent electron
collection via CdSe nanoparticles to the electrodes. Hence, the design of a more
continuous electron-transport pathway should greatly improve the performance of
hybrid solar cells in the future.
PMID- 24351094
TI - Ecological adaptation and reproductive isolation in sympatry: genetic and
phenotypic evidence for native host races of Rhagoletis pomonella.
AB - Ecological speciation with gene flow may be an important mode of diversification
for phytophagous insects. The recent shift of Rhagoletis pomonella from its
native host downy hawthorn (Crataegus mollis) to introduced apple (Malus
domestica) in the northeastern United States is a classic example of sympatric
host race formation. Here, we test whether R. pomonella has similarly formed host
races on four native Crataegus species in the southern United States: western
mayhaw (C. opaca), blueberry hawthorn (C. brachyacantha), southern red hawthorn
(C. mollis var. texana) and green hawthorn (C. viridis). These four southern
hosts differ from each other in their fruiting phenology and in the volatile
compounds emitted from the surface of their fruits. These two traits form the
basis of ecological reproductive isolation between downy hawthorn and apple flies
in the north. We report evidence from microsatellite population surveys and
eclosion studies supporting the existence of genetically differentiated and
partially reproductively isolated host races of southern hawthorn flies. The
results provide an example of host shifting and ecological divergence involving
native plants and imply that speciation with gene flow may be commonly initiated
in Rhagoletis when ecological opportunity presents itself.
PMID- 24351095
TI - Donor information based prediction of early allograft dysfunction and outcome in
liver transplantation.
AB - BACKGROUND & AIMS: Poor initial graft function was recently newly defined as
early allograft dysfunction (EAD) [Olthoff KM, Kulik L, Samstein B, et al.
Validation of a current definition of early allograft dysfunction in liver
transplant recipients and analysis of risk factors. Liver Transpl 2010; 16: 943].
Aim of this analysis was to evaluate predictive donor information for development
of EAD. METHODS: Six hundred and seventy-eight consecutive adult patients (mean
age 51.6 years; 60.3% men) who received a primary liver transplantation (LT)
(09/2003-12/2011) were included. Standard donor data were correlated with EAD and
outcome by univariable/multivariable logistic regression and Cox proportional
hazards to identify prognostic donor factors after adjustment for recipient
confounders. Estimates of relevant factors were utilized for construction of a
new continuous risk index to develop EAD. RESULTS: 38.7% patients developed EAD.
30-day survival of grafts with and without EAD was 59.8% and 89.7% (P < 0.0001).
30-day survival of patients with and without EAD was 68.5% and 93.1% (P < 0.0001)
respectively. Donor body mass index (P = 0.0112), gGT (P = 0.0471),
macrosteatosis (P = 0.0006) and cold ischaemia time (CIT) (P = 0.0031) were
predictors of EAD. Internal cross validation showed a high predictive value (c
index = 0.622). CONCLUSIONS: Early allograft dysfunction correlates with early
results of LT and can be predicted by donor data only. The newly introduced risk
index potentially optimizes individual decisions to accept/decline high risk
organs. Outcome of these organs might be improved by shortening CIT.
PMID- 24351096
TI - Joint diabetes thalassaemia clinic: an effective new model of care.
AB - Diabetes is a significant complication of beta-thalassemia major (beta-TM) and
most patients receive fragmented diabetes care. In 2005, we developed a unique
Joint Diabetes Thalassaemia Clinic, based at the Department of Diabetes,
Whittington Health, London, UK, where patients were reviewed jointly by a
multidisciplinary team, including Consultant Diabetologist and Hematologist.
Study of the Joint Diabetes Thalassaemia Clinic (2005-2009) showed improvement in
glycemic control with fructosamine reduction from 344 umol/L to 319 umol/L over a
1-year period as well as improvement in lipid profiles. The proportion of
patients attending the Joint Clinic who achieved metabolic targets compared to
the National Diabetes Audit for England was higher for glycemic control (73.0
Joint Diabetes Thalassaemia Clinic vs. 63.0% nationally), blood pressure control
(58.0 Joint Diabetes Thalassaemia Clinic vs. 30.0% nationally) and cholesterol
control (81.0 Joint Diabetes Thalassaemia Clinic vs. 78.0% nationally). Five
patients (22.7%) had microvascular complications. A significant proportion of our
patients had endocrinopathies (86.0% hypogonadism, 18.0% hypothyroidism, 23.0%
hypoparathyroidism). The unique partnership of our Joint Diabetes Thalassaemia
Clinic, allowed these very complex patients to be managed effectively.
PMID- 24351098
TI - Excited state intramolecular proton transfer in pi-expanded phenazine-derived
phenols.
AB - Two previously inaccessible analogs of 10-hydroxybenzo[h]quinoline were prepared
via a straightforward strategy comprising the formation of pi-expanded phenazines
skeleton followed by C-H acetoxylation at position 10. Two bis-phenols possessing
C2 and D2 symmetry were obtained in yields of 52% and 15%, respectively. The
occurrence of excited state intramolecular proton transfer (ESIPT) was detected
in all cases because steady state emission was observed only from the excited
keto-tautomer. Additionally, a short-lived, ~0.1 ps, emission decay was resolved
by the femtosecond up-conversion technique at the blue side of the keto-tautomer
emission band, 610 nm, and was attributed to the ESIPT, i.e., conversion from
enol to keto tautomer. In comparison with the corresponding 10
hydroxybenzo[h]quinoline emissions, the emission spectrum of the pi-expanded
phenazine analogues were weaker but displayed a characteristic bathochromically
shift into NIR region. These phenazine analogues constitute one of largest
heterocycles for which ESIPT was unambiguously detected.
PMID- 24351097
TI - Application of personalized medicine to chronic disease: a feasibility
assessment.
AB - Personalized Medicine has the potential to improve health outcomes and reduce the
cost of care; however its adoption has been slow in Canada. Bridgepoint Health is
a complex continuous care provider striving to reduce the burden of polypharmacy
in chronic patients. The main goal of the study was to explore the feasibility of
utilizing personalized medicine in the treatment of chronic complex patients as a
preliminary institutional health technology assessment. We analyzed stroke
treatment optimization as a clinical indication that could serve as a "proof of
concept" for the widespread implementation of pharmacogenetics. The objectives of
the study were three-fold:1. Review current practice in medication administration
for stroke treatment at Bridgepoint Health2. Critically analyze evidence that
pharmacogenetic testing could (or could not) enhance drug selection and treatment
efficacy for stroke patients;3. Assess the cost-benefit potential of a
pharmacogenetic intervention for stroke.Review current practice in medication
administration for stroke treatment at Bridgepoint HealthCritically analyze
evidence that pharmacogenetic testing could (or could not) enhance drug selection
and treatment efficacy for stroke patients;Assess the cost-benefit potential of a
pharmacogenetic intervention for stroke.We conducted a review of stroke treatment
practices at Bridgepoint Health, scanned the literature for drug-gene and drug
outcome interactions, and evaluated the potential consequences of pharmacogenetic
testing using the ACCE model.There is a substantial body of evidence suggesting
that pharmacogenetic stratification of stroke treatment can improve patient
outcomes in the long-term, and provide substantial efficiencies for the
healthcare system in the short-term. Specifically, pharmacogenetic stratification
of antiplatelet and anticoagulant therapies for stroke patients may have a major
impact on the risk of disease recurrence, and thus should be explored further for
clinical application. Bridgepoint Health, and other healthcare institutions
taking this path, should consider launching pilot projects to assess the
practical impact of pharmacogenetics to optimize treatment for chronic continuous
care.
PMID- 24351099
TI - Controlling gold nanoclusters by diphospine ligands.
AB - We report the synthesis and structure determination of a new Au22 nanocluster
coordinated by six bidentate diphosphine ligands: 1,8-bis(diphenylphosphino)
octane (L(8) for short). Single crystal X-ray crystallography and electrospray
ionization mass spectrometry show that the cluster assembly is neutral and can be
formulated as Au22(L(8))6. The Au22 core consists of two Au11 units clipped
together by four L(8) ligands, while the additional two ligands coordinate to
each Au11 unit in a bidentate fashion. Eight gold atoms at the interface of the
two Au11 units are not coordinated by any ligands. Four short gold-gold distances
(2.64-2.65 A) are observed at the interface of the two Au11 clusters as a result
of the clamping force of the four clipping ligands and strong electronic
interactions. The eight uncoordinated surface gold atoms in the Au22(L(8))6
nanocluster are unprecedented in atom-precise gold nanoparticles and can be
considered as potential in situ active sites for catalysis.
PMID- 24351100
TI - Low central venous pressure versus acute normovolemic hemodilution versus
conventional fluid management for reducing blood loss in radical retropubic
prostatectomy: a randomized controlled trial.
AB - OBJECTIVE: To compare acute normovolemic hemodilution versus low central venous
pressure strategy versus conventional fluid management in reducing intraoperative
estimated blood loss, hematocrit drop and need for blood transfusion in patients
undergoing radical retropubic prostatectomy under general anesthesia. RESEARCH
DESIGN AND METHODS: Patients undergoing radical retropubic prostatectomy under
general anesthesia were randomized to conventional fluid management, acute
normovolemic hemodilution or low central venous pressure (<=5 mmHg). Treatment
effects on estimated blood loss and hematocrit change were tested in
multivariable regression models accounting for surgeon, prostate size, and all
two-way interactions. RESULTS: Ninety-two patients completed the study. Estimated
blood loss (mean +/- SD) was significantly lower with low central venous pressure
(706 +/- 362 ml) compared to acute normovolemic hemodilution (1103 +/- 635 ml)
and conventional (1051 +/- 714 ml) groups (p = 0.0134). There was no difference
between the groups in need for blood transfusion, or hematocrit drop from
preoperative values. The multivariate model predicting estimated blood loss
showed a significant effect of treatment (p = 0.0028) and prostate size (p =
0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit
change, accounting for surgeon difference (p = 0.0037), the treatment effect
depended on prostate size (p = 0.0007) with the slope of low central venous
pressure differing from the other two groups. Hematocrit was predicted to drop
more with increased prostate size in acute normovolemic hemodilution and
conventional groups but not with low central venous pressure. KEY LIMITATIONS:
Limitations include the inability to blind providers to group assignment,
possible variability between providers in estimation of blood loss, and the
relatively small sample size that was not powered to detect differences between
the groups in need for blood transfusion. CONCLUSIONS: Maintaining low central
venous pressure reduced estimated blood loss compared to conventional fluid
management and acute normovolemic hemodilution in patients undergoing radical
retropubic prostatectomy but there was no difference in allogeneic blood
transfusion between the groups.
PMID- 24351101
TI - A Combined Approach for the Treatment of Resorbed Fresh Sockets Allowing
Immediate Implant Restoration: A 2-Year Follow-Up.
PMID- 24351103
TI - Serum and red blood cell folate testing for folate deficiency: new features?
AB - INTRODUCTION: Folate deficiency is assessed by serum and red blood cell folate
measurements. Nevertheless, no consensus for the lower limit of serum folate
reference values exists. We investigated the appropriate use of RBC folate to
detect folate deficiency and the relationship between serum and RBC folate and
with other parameters such as vitamin B12 and homocysteine in order to propose
serum folate cut-off values. METHODS: Retrospectively, 63,113 and 20,459 results
of serum and RBC folate were collected. If present, the results of red cell
indices, vitamin B12 and homocysteine were also collected. RESULTS: A
significantly positive correlation between serum and RBC folate was demonstrated.
A significant effect of serum folate levels under 6 MUg/L (or 14 nm) was observed
on RBC indices. A relation was found between vitamin B12 and folate, for serum
and RBC. A significant rise in homocysteine concentrations was observed for serum
folate levels under 8 MUg/L (or 18 nm). CONCLUSION: To observe haematological
abnormalities, folate deficiency should be profound. Serum folate levels under 8
MUg/L (or 18 nm) should be considered as a decision limit for folate depletion
because a positive effect on homocysteine was observed. Fasting serum folate
concentration should be preferred for assessing folate status. Our results
suggest that the need for RBC folate testing is less meaningful.
PMID- 24351102
TI - Gene variations of ROCKs and risk of ischaemic stroke: the Women's Genome Health
Study.
AB - Recent animal and human studies have demonstrated the importance of the ROCK
(RhoA/Rho-associated kinase) pathway in IsST (ischaemic stroke). Whether the
genetic variation within ROCK-associated genes modulates the risk of IsST remains
elusive. The association between 66 tSNPs [tagging SNPs (single nucleotide
polymorphisms)] of three ROCK-associated genes [ROCK1, ROCK2 and ARHGEF10 (Rho
guanine-nucleotide-exchange factor 10)] and the incidence of IsST was
investigated in 23294 Caucasian female participants of the prospective WGHS
(Women's Genome Health Study). All were free of known cancer and cardiovascular
disease at baseline. During a 15-year follow-up period, 323 participants
developed their first ever IsST. Multivariable Cox regression analysis was
performed to investigate the relationship between genotypes and risk of IsST
assuming an additive genetic model. Haplotype-block analysis was also performed.
A total of ten tSNPs were associated with the risk of IsST (three in ARHGEF10 and
seven in ROCK1; P<0.050). Further investigation using the haplotype-block
analysis revealed a similar significant association of pre-specified haplotypes
of ROCK1 with the risk of IsST (P=0.005). If corroborated in other large
prospective studies, the findings of the present study suggest that genetic
variation within the ROCK-associated pathway gene loci examined, and in
particular ROCK1 gene variation, may influence the risk of IsST.
PMID- 24351105
TI - Assessment of pattern for consumption and awareness regarding energy drinks among
medical students.
AB - BACKGROUND: Energy drink is a type of beverage which contains stimulant drugs
chiefly caffeine and marketed as mental and physical stimulator. Coffee, tea,
soft drinks and other caffeinated beverages are not considered as energy drinks.
Purpose of our study was to evaluate the awareness of medical students regarding
energy drinks and their pattern and reason of energy drinks consumption. METHODS:
This was a cross sectional and observational study conducted during the period of
January - December 2012 at four Medical Colleges (Dow Medical College, Sindh
Medical College, Jinnah Medical College and Liaquat National Medical College) of
Karachi, Pakistan. Over all 900 M.B.B.S students were invited to participate
after taking written consent but viable questionnaire was submitted by 866
students, estimated response rate of 96%. All data was entered and analyzed
through SPSS version 19. RESULT: Out of 866 participants, majority were females
614 (70.9%) and only 252 (28.5%) were males, with a mean age of 21.43 +/- 1.51
years. Energy drinks users were 350 (42.89%) and non users were 516 (59.58%).
Only 102 (29.3%) users and 159 (30.7%) non users know the correct definition of
Energy drinks. Regarding awareness, mostly user and non users thought that usage
of energy drinks had been on rise due to its usefulness in reducing sleep hours
[users193 (43.9%), nonusers 247 (56.1%) (p < 0.05)], for studying or completing
major projects [users184 (45.0%), nonusers 225 (55.0%) (p < 0.05)] and for
refreshment purposes [users179 (44.9%), nonusers 220 (55.1%) (p < 0.05)]. Two
main reasons of not using energy drinks by non-users were "awareness from its
side effects" 247 (47.8%) and "have no specific reason" 265 (51.3%). Most common
side effects reported by users were fatigue 111 (31.7%) and weight gain 102
(29.4%). CONCLUSION: In sum, the fact that despite serious side effects of weight
gaining and fatigue, practice of consuming energy drinks is highly prevalent
among medical students, particularly because they are ever ready to boost their
energy level and reduce sleep hours due to stress of exams and projects. This
warrants the creation of continued public health awareness about the appropriate
use of caffeinated beverages, their potential benefits, side effects and
correction of wrong perceptions.
PMID- 24351104
TI - Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in
three mouse models of Rett syndrome.
AB - Disturbances in respiration are common and debilitating features of Rett syndrome
(RTT). A previous study showed that the 5-HT1a receptor agonist (R)-(+)-8-hydroxy
dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) significantly reduced the
incidence of apnea and the irregular breathing pattern in a mouse model of the
disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan,
a full 5-HT1a agonist and a dopamine D2-like agonist/partial agonist, has been
used in clinical trials for the treatment of l-dopa-induced dyskinesia. The
purpose of this study was to evaluate the effects of sarizotan on respiration and
locomotion in mouse models of RTT. Studies were performed in Bird and Jaenisch
strains of methyl-CpG-binding protein 2--deficient heterozygous female and
Jaenisch strain Mecp2 null male mice and in knock-in heterozygous female mice of
a common nonsense mutation (R168X). Respiratory pattern was determined with body
plethysmography, and locomotion was determined with open-field recording.
Sarizotan or vehicle was administered 20 minutes before a 30-minute recording of
respiratory pattern or motor behavior. In separate studies, a crossover design
was used to administer the drug for 7 and for 14 days. Sarizotan reduced the
incidence of apnea in all three RTT mouse models to approximately 15% of their
pretreatment levels. The irregular breathing pattern was corrected to that of
wild-type littermates. When administered for 7 or 14 days, apnea decreased to 25
to 33% of the incidence seen with vehicle. This study indicates that the
clinically approved drug sarizotan is an effective treatment for respiratory
disorders in mouse models of RTT.
PMID- 24351106
TI - Mapping pathways to drug resistance with proteomics.
AB - Emerging drug resistance thwarts progress in chemotherapy, resulting in increased
morbidity, mortality and healthcare costs. Understanding the mechanisms by which
drug resistance phenotypes emerge is important to prolong the useful life of
existing drugs but may also highlight pathways that play a role in the
acquisition of resistance and which may themselves present resistance-proof drug
targets. Comparative proteomic approaches have demonstrated potential to link
drug resistance phenotypes to molecular changes but will also prove powerful in
the elucidation of the mechanisms by which drug resistance arises.
PMID- 24351107
TI - MrIC, a novel alpha-conotoxin agonist in the presence of PNU at endogenous alpha7
nicotinic acetylcholine receptors.
AB - alpha-Conotoxins are competitive antagonists of nicotinic acetylcholine receptors
(nAChRs). Their high selectivity and affinity for the various subtypes of nAChRs
have led to significant advances in our understanding of the structure and
function of these key ion channels. Here we report the discovery of a novel 4/7
alpha-conotoxin, MrIC from the venom duct of Conus marmoreus, which acts as an
agonist at the endogenous human alpha7 nAChR in SH-SY5Y cells pretreated with
PNU120596 (PNU). This unique agonist activity of MrIC at alpha7 nAChRs may guide
the development of novel alpha7 nAChR modulators.
PMID- 24351108
TI - Spatially correlated extinctions select for less emigration but larger dispersal
distances in the spider mite Tetranychus urticae.
AB - Dispersal is a central process to almost all species on earth, as it connects
spatially structured populations and thereby increases population persistence.
Dispersal is subject to (rapid) evolution and local patch extinctions are an
important selective force in this context. In contrast to the randomly
distributed local extinctions considered in most theoretical studies, habitat
fragmentation or other anthropogenic interventions will lead to spatially
correlated extinction patterns. Under such conditions natural selection is
thought to lead to more long-distance dispersal, but this theoretical prediction
has not yet been verified empirically. We test this prediction in experimental
spatially structured populations of the spider mite Tetranychus urticae and
supplement these empirical results with insights from an individual-based
evolutionary model. We demonstrate that the spatial correlation of local
extinctions changes the entire distribution of dispersal distances (dispersal
kernel) and selects for overall less emigration but more long-distance dispersal.
PMID- 24351109
TI - The relationship among depression, parenting stress, and partner support in low
income women from Montevideo, Uruguay.
AB - We investigated the prevalence and predictors of depression in low-income mothers
(n = 99) of young children from Uruguay. We administered the Beck Depression
Scale (BDI) and the Parenting Stress Index (PSI), and asked who is responsible
for the main tasks of parenting and household care. We found a high prevalence of
moderate-to-severe depression (BDI >19 points, 31.3%), with women with t scores >
90 on the PSI being seven times more likely to experience moderate-to-severe
depressive symptoms than women with lower PSI scores (p <.01). This is the first
investigation of the predictors of depression in urban Uruguayan mothers of low
socioeconomic status.
PMID- 24351110
TI - Brown carbon formation by aqueous-phase carbonyl compound reactions with amines
and ammonium sulfate.
AB - Reactions between small water-soluble carbonyl compounds, ammonium sulfate (AS),
and/or amines were evaluated for their ability to form light-absorbing species in
aqueous aerosol. Aerosol chemistry was simulated with bulk phase reactions at pH
4, 275 K, initial concentrations of 0.05 to 0.25 M, and UV-vis and fluorescence
spectroscopy monitoring. Glycolaldehyde-glycine mixtures produced the most
intense absorbance. In carbonyl compound reactions with AS, methylamine, or
AS/glycine mixtures, product absorbance followed the order methylglyoxal >
glyoxal > glycolaldehyde > hydroxyacetone. Absorbance extended into the visible,
with a wavelength dependence fit by absorption Angstrom coefficients (A(abs)) of
2 to 11, overlapping the A(abs) range of atmospheric, water-soluble brown carbon.
Many reaction products absorbing between 300 and 400 nm were strongly
fluorescent. On a per mole basis, amines are much more effective than AS at
producing brown carbon. In addition, methylglyoxal and glyoxal produced more
light-absorbing products in reactions with a 5:1 AS-glycine mixture than with AS
or glycine alone, illustrating the importance of both organic and inorganic
nitrogen in brown carbon formation. Through comparison to biomass burning
aerosol, we place an upper limit on the contribution of these aqueous carbonyl-AS
amine reactions of <= 10% of global light absorption by brown carbon.
PMID- 24351111
TI - Metal-free direct intramolecular carbotrifluoromethylation of alkenes to
functionalized trifluoromethyl azaheterocycles.
AB - The first example of a metal-free direct carbotrifluoromethylation of alkenes
using inexpensive TMSCF3 as the CF3 source is described. The methodology not only
exhibits high chemoselectivity for this transformation but also expands the
substrate scope that is difficult to access by known transition-metal-catalyzed
methods.
PMID- 24351112
TI - Telbivudine protects renal function in patients with chronic hepatitis B
infection in conjunction with adefovir-based combination therapy.
AB - Previous studies have demonstrated that the treatment of chronic hepatitis B
(CHB) infection with adefovir (ADV) can impair renal function. In contrast,
treatment with telbivudine (LdT) improves renal function in CHB patients. The aim
of this study was to evaluate the renoprotective effect of LdT in CHB patients
receiving ADV-based combination therapy. The effects of treatment with ADV + LdT
on renal function were compared to those resulting from treatment with ADV +
entecavir (ETV), ADV + lamivudine (LAM), ADV alone and ETV alone. The consecutive
cohort analysis included 831 CHB patients who received ADV + LdT, ADV + LAM, ADV
+ ETV, ADV alone or ETV alone for 96 weeks. Alterations in estimated glomerular
filtration rate (eGFR) were compared between the five groups using a linear mixed
effects model. HBV DNA levels were also compared between the five groups during
the 96-week period. Among the five treatment groups, significant improvements in
eGFR were observed in the ADV + LdT and ADV + LAM groups over time (P < 0.001 for
each group compared with baseline eGFR). In patients with a baseline eGFR between
50 and 90 mL/min, the change in eGFR was the most significant in the ADV + LdT
group (+0.641 mL/min; P < 0.001). Age, gender, baseline eGFR and treatment option
were significant predictive factors for eGFR changes. In conclusion, our results
suggest that the combination therapy of LdT and ADV is significantly associated
with renoprotective effects in CHB patients when compared with other ADV-based
combination or single therapies.
PMID- 24351113
TI - Implementation of a blended learning approach to teaching evidence based
practice: a protocol for a mixed methods study.
AB - BACKGROUND: Evidence based practice (EBP) requires that health professionals are
competent in integrating the best evidence in their decision making. Being
'evidence-based' requires skills and knowledge in epidemiology, biostatistics and
information literacy. EBP is commonly taught in medical and health sciences
degrees, yet there is little evidence to guide educators as to the best teaching
modality to increase learner competency in EBP. METHODS/DESIGN: This study is
mixed methods in design. A randomised controlled trial will examine the
effectiveness of blended learning versus didactic approach of teaching EBP to
medical students. The primary outcome of the RCT is EBP competency as assessed by
the Berlin tool. Focus groups will be conducted to explore student perceptions
and attitudes towards implementing a blended learning approach in teaching EBP. A
concurrent triangulation design will be implemented, permitting quantitative data
to inform the effectiveness of the intervention and qualitative data to
contextualise the results. DISCUSSION: This study will provide novel evidence on
the effectiveness of blended learning in teaching EBP to a cohort of
undergraduate and graduate-entry medical students.
PMID- 24351114
TI - Actin reorganization through dynamic interactions with single-wall carbon
nanotubes.
AB - Single-wall carbon nanotubes (SWCNTs) have been widely used for biological
applications in recent years, and thus, it is critical to understand how these
inert nanomaterials influence cell behavior. Recently, it has been observed that
cellular phenotypes such as proliferation, force generation and growth change
upon SWCNT treatment, and SWCNTs directly affect the organization and
redistribution of the actin cytoskeleton. However, the interactions between
SWCNTs and actin at the molecular level or how this interaction changes actin
structure remain largely unknown. Here, we investigated direct interaction of
actin with SWCNT using all-atom molecular dynamics simulations and NIR
spectroscopy of actin-dispersed SWCNTs. Actin can stably bind to the SWCNT
surfaces via hydrophobic interactions but still allows nanotubes to slide and
rotate on the actin surface. Our results establish several nanoscale
conformational changes for the actin-SWCNT complexes, and we suggest these
changes likely induce reorganization of actin filaments observed at larger
scales.
PMID- 24351115
TI - Microstructure and mechanical properties of in situ Streptococcus mutans
biofilms.
AB - Insight into live microbial biofilm microstructure and mechanical properties and
their interactions with the underlying substrate can lead to the development of
new remedial strategies and/or materials. Here we report mechanical properties of
dental pathogenic Streptococcus mutans biofilms, grown on a polystyrene-coated
plate of a shear rheometer in physiologically relevant conditions, precisely
controlled in a custom built bioreactor. In situ measurements demonstrated the
importance of microstructure and composition of extracellular polymeric
substances on the biofilm modulus. The biofilms behave like a weak gel with
storage moduli higher than loss moduli. The simple but robust experimental
technique presented here can easily be extended to other biofilm-material
systems.
PMID- 24351117
TI - Oral Pyogenic Granuloma Associated With a Dental Implant Treated With an Er:YAG
Laser: A Case Report.
AB - A pyogenic granuloma is a tumorlike proliferation that occurs slightly more often
in females, frequently involving the gingiva in the maxillary region. Clinically,
it presents as a sessile or pedunculated exophytic mass with a smooth or
lobulated surface, which tends to bleed easily. Its color can range from pink to
dark red. The most common treatment is surgical excision. This case report
presents a pyogenic granuloma that formed around an implant 7 years after its
insertion. Pyogenic granulomas associated with dental implants are extremely
rare; this is the fourth reported case and the first case of pyogenic granuloma
to be treated with an Er:YAG laser.
PMID- 24351116
TI - Expression and prognostic relevance of cyclophilin A and matrix metalloproteinase
9 in esophageal squamous cell carcinoma.
AB - AIMS: To guide clinicians in selecting treatment options for esophageal squamous
cell carcinoma (ESCC) patients, reliable markers predictive of clinical outcome
are desirable. This study analyzed the correlation of cyclophilin A (CypA) and
matrix metalloproteinase 9 (MMP9) in ESCC and their relationships to
clinicopathological features and survival. METHODS: We immunohistochemically
investigated 70 specimens of ESCC tissues using CypA and MMP9 antibodies. Then,
the correlations between CypA and MMP9 expression and clinicopathological
features and its prognostic relevance were determined. RESULTS: Significant
correlations were only found in high level of CypA and MMP9 expression with tumor
differentiation and lymph node status. Significant positive correlations were
found between the expression status of CypA and that of MMP9. Overexpression of
CypA and metastasis were significantly associated with shorter progression free
survival times in univariate analysis. Multivariate analysis confirmed that CypA
expression was an independent prognostic factor. CONCLUSIONS: CypA might be
correlated with the differentiation, and its elevated expression may be an
adverse prognostic indicator for the patients of ESCC. CypA/MMP9 signal pathway
may be attributed to the malignant transformation of ESCC, and attention should
be paid to a possible target for therapy. VIRTUAL SLIDES: The virtual slide(s)
for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1166551968105508.
PMID- 24351118
TI - Severe alpha-thalassemia intermedia due to a compound heterozygosity for the
highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A)
mutation.
AB - We report a novel mutation at codon 24 of the alpha2-globin gene (HBA2: c.75T >
A) found in a Sundanese family. This novel mutation was detected during prenatal
diagnosis. The couple already had a 7-year-old boy who exhibited clinically
severe alpha-thalassemia intermedia (alpha-TI), and he was found to be a compound
heterozygote for the novel mutation at codon 24 and the previously described Hb
Adana (HBA2: c.179G > A) at codon 59 of the alpha2-globin gene. The father was a
carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low
mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.
PMID- 24351119
TI - The growing number of female physicians: meanings, values, and outcomes.
AB - Throughout the developed world the proportion of women in professions such as
medicine is increasing. This commentary uses Haklai et al's nuanced report on the
feminization of medicine in Israel as a starting point. I discuss whether gender
shifts are an outcome of more egalitarian attitudes towards women overall, or
instead arise from men choosing other professions, the extent of the shift, and
its meaning for the quantity and quality of medical care. The discussion is
embedded in more fundamental concepts such as the aims of medical practice and
the best indicators of effective care. I reflect on concerns about lower female
physician productivity at a time when the proportion of female physicians still
remains below parity in almost all countries. Medicine is embedded in the
principles and expectations of the community being served. The profession's
values and practices both shape and are shaped by those of that larger community.
As cultures move toward equality, proportional representation of women and men in
medicine will follow, while remaining limitations to gender equality will be
mirrored in opportunities and restrictions for women in medicine. This is a
commentary on http://www.ijhpr.org/content/2/1/37/.
PMID- 24351120
TI - Revisiting comparisons of genetic diversity in stable and declining species:
assessing genome-wide polymorphism in North American bumble bees using RAD
sequencing.
AB - Genetic variation is of key importance for a species' evolutionary potential, and
its estimation is a major component of conservation studies. New DNA sequencing
technologies have enabled the analysis of large portions of the genome in
nonmodel species, promising highly accurate estimates of such population genetic
parameters. Restriction site-associated DNA sequencing (RADseq) is used to
analyse thousands of variants in the bumble bee species Bombus impatiens, which
is common, and Bombus pensylvanicus, which is in decline. Previous microsatellite
based analyses have shown that gene diversity is lower in the declining B.
pensylvanicus than in B. impatiens. RADseq nucleotide diversities appear much
more similar in the two species. Both species exhibit allele frequencies
consistent with historical population expansions. Differences in diversity
observed at microsatellites thus do not appear to have arisen from long-term
differences in population size and are either recent in origin or may result from
mutational processes. Additional research is needed to explain these
discrepancies and to investigate the best ways to integrate next-generation
sequencing data and more traditional molecular markers in studies of genetic
diversity.
PMID- 24351121
TI - Confinement of water in hydrophobic nanopores: effect of the geometry on the
energy of intrusion.
AB - Water confinement in the hydrophobic nanopores of highly siliceous zeolite having
MFI and CHA topology is investigated by high pressure manometry coupled to
differential calorimetry. Surprisingly, the intrusion of water is endothermic for
MFI but exothermic for CHA. This phase transition depends on the geometry of the
environment in which water is confined: channels (MFI) or cavities (CHA). The
energy of intrusion is mainly governed by the change in the coordination of water
molecules when they are forced to enter the nanopores and to adopt a weaker,
hydrogen-bonded structure. At such a nanoscale, the properties of the molecules
are governed strongly by geometrical restraints. This implies that the use of
classical macroscopic equations such as Laplace-Washburn will have limitations at
the molecular level.
PMID- 24351122
TI - Treatment and outcome of patients with metastatic NSCLC: a retrospective
institution analysis of 493 patients.
AB - BACKGROUND: Most patients with metastatic non-small cell lung cancer (NSCLC) will
face treatment with systemic therapy. Current clinical studies are demonstrating
improvements in chemotherapy and overall survival. However, it remains unclear
whether these results are translated into clinical practice. METHODS: We reviewed
all stage IV NSCLC patients without second malignancies that were diagnosed from
2004 to 2006 at our institution. 493 consecutive patients were included into this
retrospective analysis and were followed-up until end of 2011. RESULTS: 352
patients (71.4%) received systemic therapy for up to 7 lines. For most patients,
adjustments of dosages or applications had to be made at some point of the
treatment, but the total applied dose remained generally close to the intended
dose. The best disease control (BDC) rate decreased with increasing therapy lines
from 59.7% to about 35%. Patients with palliative local therapy but no systemic
treatment demonstrated inferior survival (median 2.9 versus 8.7 months, p <
0.001). The median interval between last treatment and death was 50 days and 15
days for chemotherapy and anti-EGFR therapy, respectively. BDC to the previous
therapy lines was predictive for improved BDC to third- but not second-line
therapy. Performing multivariate analysis, BDC to previous therapy, never-/
former-smoking status, and age > 70 years were associated with improved survival
performing third-line therapy. CONCLUSIONS: Stage IV NSCLC patients may receive
substantial systemic therapy resulting in response and median survival rates that
are comparable to data from clinical studies. However, preselection factors are
increasingly important to improve therapy outcome and life quality.
PMID- 24351123
TI - Clinical characteristics of patients after dicamba herbicide ingestion.
AB - OBJECTIVE: Despite a widespread use of dicamba herbicide and numerous animal
model studies, there had not been studies on acute toxicity of this chemical
compound in human subjects following ingestion. Therefore, this study was
conducted to investigate clinical characteristics of dicamba poisoning and to
guide physicians treating patients intoxicated with dicamba herbicide. MATERIAL
AND METHOD: A retrospective observational case series was conducted for 14
patients with history of dicamba herbicide ingestion. Data were collected for
clinical manifestation, patient management, and final outcome. RESULT: The most
common symptom was altered mental state (Glasgow Coma Scale <= 14). Laboratory
abnormalities were elevations in lactate, and creatine kinase, metabolic acidosis
(pH < 7.35, and HCO3(-) < 20 mmol/L), and elevated lipase. QTc prolongation was
commonly observed. These abnormal clinical findings had normalized within two
days of supportive treatment after dicamba ingestion. One patient did demonstrate
corrosive esophagitis. DISCUSSION AND CONCLUSION: Acute toxicity of dicamba
herbicide in human following oral exposure was manageable with supportive
treatment. However, physician should take into account for corrosive effect on GI
tract, rhabdomyolysis, or acute pancreatitis.
PMID- 24351124
TI - A functional polymorphism in ADAR1 gene affects HBsAg seroclearance both
spontaneously and interferon induced.
AB - BACKGROUND & AIMS: Our previous study found that rs4845384 in ADAR1 gene to be
associated with HBeAg seroconversion. However, the effect of rs4845384 on HBsAg
seroclearance is unknown. To assess the relationship between rs4845384 and HBsAg
seroclearance. METHODS: Two independent case-control studies were conducted to
test whether rs4845384 in ADAR1 was associated with HBsAg clearance. Reporter
gene assays and quantitative PCR experiments were also carried out to verify the
functional significances of this polymorphism. RESULTS AND CONCLUSIONS: The
rs4845384 polymorphism was associated with HBsAg seroclearance both spontaneously
(P = 0.028, OR = 1.36, 95% CI = 1.03-1.78) and interferon induced (P = 0.013, OR
= 1.83, 95% CI = 1.13-2.96), in a total of 725 subjects. Luciferase assays showed
that pGL3-rs4845384G constructs had higher expression level than pGL3-rs4845384A
constructs, especially in HepG2. 2.15 cell line. Quantitative real-time RT-PCR
showed that chronic hepatitis B (CHB) patients had lower ADAR1 mRNA level than
healthy individuals. The AA carriers of rs4845384 had lower ADAR1 mRNA expression
than non-AA carriers. The non-response susceptible allele rs4845384A was
functional for regulation of ADAR1 expression, so as to influence HBsAg
seroclearance of CHB patients.
PMID- 24351125
TI - The FICA Spiritual History Tool #274.
PMID- 24351127
TI - End-of-life and advance care planning considerations for lesbian, gay, bisexual,
and transgender patients #275.
PMID- 24351126
TI - Exploring the collective hospice caregiving experience.
AB - BACKGROUND: Collective caregiving, performed by caregivers working in pairs
(informal primary and secondary caregivers working together), is common in the
hospice setting. Research suggests that caregiving pairs may experience different
caregiver outcomes. However, little is known about how caregiving pairs differ
from solo caregivers (informal primary caregivers) on outcome measures.
OBJECTIVE: The goal of this study was to determine whether being in a caregiver
pair affected caregiver anxiety and depression and how outcomes changed over
time. DESIGN: A mixed model analysis was used. SETTING/SUBJECTS: Hospice
caregivers (260 solo caregivers and 44 caregivers in 22 pairs) who participated
in a larger, randomized controlled trial completed caregiver measures upon
hospice admission and periodically until the death of the patient or hospice
decertification. MEASUREMENTS: Measured were caregiver quality of life, social
support, anxiety, and depression. RESULTS: Caregiver pairs had higher anxiety and
depression scores than solo caregivers. Emotional, financial, and physical
quality of life were associated with decreased depression, whereas only emotional
and financial quality of life were correlated with lower levels of anxiety.
Social support was associated with lower levels of depression and anxiety.
CONCLUSIONS: Despite assumptions that social support is positively facilitated
vis-a-vis collective caregiving, caregiving pairs may be at higher risk for
anxiety and depression. Future research is needed to address why individuals
become anxious and/or depressed when working as part of a caregiving pair.
PMID- 24351128
TI - Managing overactive bladder symptoms in a palliative care setting.
AB - BACKGROUND: The combined symptoms of urinary frequency, urgency, nocturia, and
incontinence (overactive bladder) are common symptoms within an elderly
population but are also seen in palliative care patients and are most often due
to detrusor muscle overactivity. These symptoms can lead to a marked reduction in
quality of life and pharmacological management is traditionally with
anticholinergic drugs. These medications carry a high risk of side effects and
are often poorly tolerated by palliative care patients. Other management
approaches, however, such as the use of urisheaths may markedly improve quality
of life without adding to symptom burden in patients nearing the end of life.
OBJECTIVES: This article highlights two cases in palliative care where overactive
bladder symptoms prove difficult to manage with anticholinergic drugs.
CONCLUSIONS: The discussion will give an overview of treatment strategies to help
aid the clinician in managing these difficult symptoms in patients with a
terminal illness.
PMID- 24351129
TI - Use of the Physician Orders for Life-Sustaining Treatment program for patients
being discharged from the hospital to the nursing facility.
AB - BACKGROUND: The Physician Orders for Life-Sustaining Treatment (POLST) documents
patient preferences as medical orders that transfer across settings with
patients. OBJECTIVES: The objectives were to pilot test methods and gather
preliminary data about POLST including (1) use at time of hospital discharge, (2)
transfers across settings, and (3) consistency with prior decisions. STUDY
DESIGN: Descriptive with chart abstraction and interviews. PARTICIPANTS:
Participants were hospitalized patients discharged to a nursing facility and/or
their surrogates in La Crosse County, Wisconsin. MEASUREMENTS: POLST forms were
abstracted from hospital records for 151 patients. Hospital and nursing facility
chart data were abstracted and interviews were conducted with an additional 39
patients/surrogates. RESULTS: Overall, 176 patients had valid POLST forms at the
time of discharge from the hospital, and many (38.6%; 68/176) only documented
code status. When the whole POLST was completed, orders were more often marked as
based on a discussion with the patient and/or surrogate than when the form was
used just for code status (95.1% versus 13.8%, p<.001). In the follow-up and
interview sample, a majority (90.6%; 29/32) of POLST forms written in the
hospital were unchanged up to three weeks after nursing facility admission. Most
(71.9%; 23/32) appeared consistent with patient or surrogate recall of prior
treatment decisions. CONCLUSION: POLST forms generated in the hospital do
transfer with patients across settings, but are often used only to document code
status. POLST orders appeared largely consistent with prior treatment decisions.
Further research is needed to assess the quality of POLST decisions.
PMID- 24351130
TI - Effects of tyramine and 4-aminophenol on the oscillating peroxidase-oxidase
reaction.
AB - The peroxidase-oxidase oscillator, a model of biological oscillations, is usually
studied in conjunction with the effector molecule, 2,4-dichlorophenol. In this
account, we present evidence of the effects of a naturally occurring phenol,
tyramine, on the reaction, and also those of the structurally similar 4
aminophenol. Whereas 2,4-dichlorophenol gives rise to sustained oscillations at
40 MUM, it was discovered that tyramine promotes damped oscillations at a
concentration of 120 MUM. Oxidation of NADH was completely inhibited by 4
aminophenol and ascorbate. In separate experiments, the peroxidase-catalyzed ring
coupling of tyramine and 4-aminophenol was observed, which in the case of
tyramine, may provide an explanation for the damping of oscillations.
PMID- 24351131
TI - Prevalence of the posterior superior alveolar canal in cone beam computed
tomography scans.
AB - OBJECTIVE: This study was primarily aimed at determining the prevalence of the
posterior superior alveolar (PSA) canal in cone beam computerized tomography
(CBCT) scans in a North American population. MATERIALS AND METHODS: Cone beam
computed tomography scans were selected on the basis of predetermined eligibility
criteria from a pool of 976 data sets. Two calibrated examiners assessed the
presence of PSA canal on the postero-lateral wall of the maxillary sinus using
coronal sections. One examiner also recorded the presence of images compatible
with sinus disease. Associations between the presence of PSA canal and sinus
disease were investigated for males and females separately using statistical
methods. RESULTS: A total of 254 CBCT scans were selected. The pooled prevalence
of the PSA canal in CBCT scans was 94.4% and 91% on the right and left side,
respectively. The ability to detect the presence of the canal was not
significantly affected by the presence of intrasinusal disease. Males are more
likely than females to present signs of maxillary sinus pathoses on the right
(63.3% vs. 36.7%) and the left side (59.2% vs. 40.8%). CONCLUSIONS: The
prevalence of the PSA canal on CBCT images in the selected population is high.
The PSA canal can be consistently visualized on CBCT scans with a high level of
reproducibility regardless of the presence of radiographic signs of intrasinusal
pathoses.
PMID- 24351132
TI - Autotandem catalysis with ruthenium: remote hydroesterification of allylic
amides.
AB - A one-pot tandem sequence involving olefin isomerization and hydroesterification
has been developed that enables the incorporation of a C1-unit at the remote
terminal position of allylic amides. Key observations suggest that generation of
an active ruthenium hydride, formed by addition of acetic acid, allows both
processes to take place under mild conditions in an autotandem catalytic,
cascading fashion, which is characterized by the use of a single catalytic entity
capable of promoting multiple distinct steps without operator intervention.
PMID- 24351133
TI - Descending necrotizing mediastinitis: a modified algorithmic approach to define a
new standard of care.
AB - BACKGROUND: Descending necrotizing mediastinitis (DNM) is a highly morbid
infectious process. This uncommon disease process has carried historically a
substantial burden of morbidity and mortality. In this study we hypothesized that
application of a prospective modified management algorithm would decrease the
morbidity and mortality from this highly destructive process. METHODS: We
developed a systematic approach for managing DNM, focusing on serial debridement
guided by imaging, in conjunction with the use of broad-spectrum antibiotics and
modern principles of critical care. We reviewed all patients admitted with this
disease process from 2007-2012. Data collected included demographic information,
co-morbidities, laboratory data including culture results, operative details,
imaging frequency and findings, complications, and survival. Continuous variables
were reported as median values and ranges. RESULTS: From 2007-2010, we treated
eight patients with DNM. The median age of the patients was 33 y (range 28-63 y),
and 63% were male. In accordance with our algorithm, the patients underwent
serial imaging at regular intervals following operative debridement. The median
number of imaging studies was 11 (range 4-19). The patients required a median of
five operative debridements (range 1-15). In five patients, drainage was
necessary through a cervical exploration. A thoracic approach was required in six
patients (two thoracoscopic, four via thoracotomy). Additional procedures
included thymectomy (n=2), anterior mediastinotomy, carotid sheath exploration
and resections of the clavicle, first rib, manubrium, pectoralis major muscle,
and sternocleidomastoid muscle. The most common etiologic agents were
Peptostreptococcus spp. and Streptococcus anginosus. Study patients received a
median of six different antibiotics (range 2-10) for a total of 42 d (range 34-55
d). These patients were hospitalized for a median of 29 days (range 16-56 d),
with 15 d (range 7-48 d) spent in the intensive care unit. Remarkably, the rate
of survival was 100% (median follow-up of 33 mo). The patients developed no major
complications, required no re-admissions, and had no re-infections. CONCLUSIONS:
We applied an algorithmic approach to the treatment of DNM, consisting of
aggressive operative debridement and enhanced by equally aggressive imaging. Our
patients had excellent outcomes despite the widely known lethality of DNM. An
aggressive approach may decrease complications and improve survival in this
devastating disease process. Furthermore, our prospective experience with DNM
suggests that this algorithm used in the present study should be the standard for
managing patients with this challenging condition.
PMID- 24351134
TI - Switching mechanism in single-layer molybdenum disulfide transistors: an insight
into current flow across Schottky barriers.
AB - In this article, we study the properties of metal contacts to single-layer
molybdenum disulfide (MoS2) crystals, revealing the nature of switching mechanism
in MoS2 transistors. On investigating transistor behavior as contact length
changes, we find that the contact resistivity for metal/MoS2 junctions is defined
by contact area instead of contact width. The minimum gate dependent transfer
length is ~0.63 MUm in the on-state for metal (Ti) contacted single-layer MoS2.
These results reveal that MoS2 transistors are Schottky barrier transistors,
where the on/off states are switched by the tuning of the Schottky barriers at
contacts. The effective barrier heights for source and drain barriers are
primarily controlled by gate and drain biases, respectively. We discuss the drain
induced barrier narrowing effect for short channel devices, which may reduce the
influence of large contact resistance for MoS2 Schottky barrier transistors at
the channel length scaling limit.
PMID- 24351135
TI - Mechanisms of physically irreversible fouling during surface water
microfiltration and mitigation by aluminum electroflotation pretreatment.
AB - A modified poly(vinylidene fluoride) membrane was used to directly microfilter
untreated Lake Houston water, which was then regenerated by surface washing and
hydraulic backwashing, a process that was cycled five times. The source water was
also electrochemically precoagulated using aluminum and microfiltered, and the
membrane was physically regenerated for five cycles. Attenuated total reflectance
Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron
spectroscopy (XPS) were used to characterize foulants on membrane surfaces and
rigorously deduce their contributions to physically irreversible fouling after
cycles 1 and 5. Hydrophobic molecules primarily appeared to initiate fouling
during microfiltration of untreated raw water because O-H/N-H bands were
attenuated while C-H bands remained relatively unchanged in FTIR-spectra of
membrane surfaces after only one cycle. However, O-H/N-H and symmetric and
asymmetric C(? O)O(-) stretching bands significantly intensified with continued
filtration/regeneration of untreated water, showing the importance of hydrophilic
molecules and the role of complexation, respectively, to longer term irreversible
fouling. Distinct C-H bands were detected in floated flocs after electrolysis,
suggesting the sorption and subsequent removal of a substantial portion of the
hydrophobic moieties present in Lake Houston water during pretreatment.
Consequently, hydrophilic compounds appeared to contribute more to irreversible
fouling in pretreated waters throughout the course of filtration as evidenced by
significantly more intense O-H bands (compared with C-H bands) on the membrane
surface after cycles 1 and 5. Therefore, electroflotation pretreatment reduced
accumulation of hydrophobic foulants but simultaneously increased complexation of
hydrophilic foulant molecules along with any carried-over aluminum hydroxide
precipitates evidenced by increasing Al and O concentrations via XPS and intense
C(? O)O(-) stretching bands in IR spectra.
PMID- 24351136
TI - Newly released data from the revised U.S. birth certificate, 2011.
AB - OBJECTIVES: This report is the first release of multistate data for selected
items exclusive to the 2003 revision of the U.S. Standard Certificate of Live
Birth. Included is information for prepregnancy body mass index, smoking and
quitting smoking in the 3 months prior to pregnancy, receipt of food from the
Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
during pregnancy, pregnancy resulting from infertility treatment, source of
payment for delivery, and maternal morbidities. METHODS: Descriptive statistics
are presented for 100% of 2011 births to residents of the 36 states, the District
of Columbia (D.C.), and Puerto Rico that had implemented the revised birth
certificate by January 1, 2011. This reporting area is not a random sample, and
results are not generalizable to the United States as a whole. RESULTS: The
3,267,934 births to residents of the 36-state and D.C. reporting area represented
83% of all 2011 U.S. births. Levels of prepregnancy obesity ranged from 18.0% in
Utah to 28.6% in South Carolina. Hispanic women were the least likely to smoke in
the 3 months prior to pregnancy and were the most likely to quit smoking prior to
pregnancy. Women under age 20 were more than twice as likely to receive WIC food
during pregnancy as women aged 35 and over in nearly all states and D.C. The
percentage of births resulting from infertility treatment ranged from 0.3% in New
Mexico to over 3.5% in Maryland and Utah. The percentage of deliveries covered by
Medicaid ranged from 28.8% in North Dakota to 64.2% in Louisiana.
PMID- 24351137
TI - The trans fatty acid and positional (sn-2) fatty acid composition of some
Australian margarines, dairy blends and animal fats.
AB - We have analysed the fatty acid (FA) composition including the trans fatty acid
by GLC and Fourier Transform Infra-Red (FTIR) Spectrophotometry of 13 margarines,
five butter/dairy blends and two animal fats (lard and dripping). The samples
were purchased from supermarkets in three separate locations across Victoria:
Gladstone Park (near Melbourne), Waurn Ponds (near Geelong) and Geelong city.
From the FA composition, the P/S, P/(S+trans monoenoic FA), P/M(S+trans monoenoic
FA) and w6/w3 ratios were calculated. The FA composition and trans FA content
were compared with the last published analysis of Australian margarines in Sydney
in 1982. The FA composition of the sn-2 position was obtained by pancreatic
lipase deacylation of the whole triglycerides (TG) . From this data, we estimated
the per cent interesterified fat which was present in the margarines. The trans
FA content of the margarines which was determined by FTIR ranged from 9.2% to
16.3% (mean of 13.1% of total FAME) (7.6 g-13.0 g trans FA/100 g sample, mean of
10.4 g/100 g sample) and from 3.2% to 4.1% (mean of 3.8%) for butter and dairy
blends. Lard contained 0.4% trans FA while dripping consisted of 3.6% trans FA.
The trans FA content in the margarines was similar to the values published in
1982 with the exception of four brands. The w6/w3 ranged from 2.5 to 363 and the
P/S ranged from 1.4 to 3.3 compared with the 1982 figures where the w6/w3 ranged
from 3 to 49 and the P/S ranged from 0.1 to 3.7. The estimated per cent
interesterified fat in the margarines ranged from 25% to 100%. We estimated the
total trans FA intake in the Australian diet to be between 2.7 g/head/day and 4.8
g/head/day. We also estimated that table margarines account for between 36% and
64% of the total trans FA intake in the Australian diet.
PMID- 24351138
TI - Trans fatty acid content of margarines, oils and blended spreads available in New
Zealand.
AB - Concern has been expressed about the possible adverse effects of high intakes of
trans fatty acids on coronary heart disease risk. Data on New Zealand foods was
very sparse. The fatty acid composition of New Zealand margarines, cooking oils,
blended spreads and dairy products has thus been analysed using a methodology
that determines the percentage of trans fatty acids. The C18: 1 trans content of
the margarines varied between 4.8% and 11.3% of the total fatty acids, and there
was less than 0.7% C18:2 trans. The total trans fatty acid content of the oils
analysed was less than 1%. The amount of trans fatty acids in readily available
margarines, blended spreads and oils in New Zealand appears lower than for many
other countries, and the intake of these products is relatively small. Most of
the products also have a high linoleic acid content, which may modify any
potential adverse effects of trans fatty acids on plasma lipoproteins.
Replacement of products high in C12, C14 and C16 saturated fatty acids in the
diet with these margarines need not be discouraged, although manufacturers should
probably be encouraged to further reduce the content of trans fatty acids of some
products and the increased use of partially hydrogenated fats in fast food
restaurants should be examined.
PMID- 24351139
TI - Body composition of Indonesian adults assessed by skinfold thickness and
bioelectrical impedance measurements and by a body mass index equation.
AB - Body composition was assessed in Indonesian male (n=29) and female (n=17)
students and rural women (n=35) using skinfold thickness measurements,
bioelectrical impedance measurements (BIA) with two different equations, and a
body mass index equation. Correlation between different methods was significant
(P<0.01). In rural women and female students fat mass by skinfold measurements
was respectively 2.5+/- 2.9 kg (P<0.01) and 2.2+/- 2.3 kg (P<0.01) lower than by
BIA. In male students the difference between skinfold and BIA measurements was
0.8+/- 2.6 kg. Disagreement between methods increased with larger fat mass. In
some individuals differences between assessed values were substantial. It is
concluded that, especially under field conditions, results obtained by different
methods are not interchangeable.
PMID- 24351140
TI - Effect of iron supplementation on biochemical indices of iron status in selected
pre-adolescent schoolgirls in North West Frontier Province, Pakistan.
AB - A study was carried out on eight to 11 year old schoolgirls to assess the
prevalence of iron deficiency anemia (IDA) and to study the impact of iron
supplementation on the biochemical indices of iron status. The children were
characterized iron deficient anemic if their serum ferritin levels (SF) were <=
12 ng/ml and hemoglobin (Hb) < 12 g/dl or hematocrit (Hct) <= 35%. In a double
blind trial, the anemic and non-anemic children were randomly selected for the
treatment and control groups. All the groups received multivitamin tablets daily,
the treatment group received an additional 76 mg elemental iron per day for 11
weeks. The prevalence of IDA in these children was found to be 35% . The
supplementation caused a significantly (P<0.05) greater change in SF (20 ng/ml);
Hb (1.5 g/dl) and Hct (3%) of the anemic treatment group compared to the
corresponding control group. The non-anemic treatment group also showed a
significantly greater change in SF (9 ng/ml); Hb (0.78 g/ dl) and Hct (1.3%) than
that of the control group. An increase in biochemical indices of the nonanemic
treatment indicates that this group's initial iron status was only marginally
adequate.
PMID- 24351141
TI - Requirements of calcium: are there ethnic differences?
AB - Calcium is an essential dietary element to maintain the integrity of the
skeleton. A higher peak adult bone mass has been shown to reduce the risk of
osteoporotic fractures later in life. It is postulated that a lifelong higher
calcium intake would reduce bone loss in advancing age. Available scientific
evidence seems to indicate that within any ethnic group, calcium intake is
positively associated with bone mass. Controlled calcium supplementation trials
in both low and high dietary calcium intake children and adolescents showed that
there is an association between calcium intake and gains in bone mass.
Furthermore, studies in adolescents showed that genetic inheritance and skeletal
responses to hormonal changes at puberty have great influences on bone mass
increments in addition to calcium intake. Interestingly, across-cultural
comparisons are not convincing enough to demonstrate that lower calcium intake
would predispose to higher risk of osteoporosis. It implies that the genetic
inheritance and complex environmental factors may be important modulators on bone
mass achievement in addition to calcium intake within any ethnic group. There are
pitfalls in the current Recommended Dietary Allowances (RDAs) for calcium which
are usually based on clinical studies conducted in Caucasians with higher calcium
intakes and the extent of nutritional adaptation to low calcium intake is
ignored. Given the fact that there are ethnic differences in calcium absorption,
dietary habits, bone metabolism, physical activity and skeletal size as well as
body build, the requirements of calcium in Asians may be different from
Caucasians. Ideally, each nation should establish its own RDA based on the ethnic
make-up of its population. In Asian countries, the major sources of calcium are
derived from vegetable types of foods, fish and shell fish with edible bones,
fins and shells, etc. Recent absorption studies in humans with low-oxalate and
low-phytate vegetables and pulses also showed that contrary to common
presuppositions, these vegetables with low calcium chelators do have a comparable
calcium absorbability to milk. Studies on bioavailability of calcium from Asian
foods and diets are warranted in order to identify rich sources of calcium.
PMID- 24351142
TI - Preferred meal patterns in non-insulin-dependent diabetes.
AB - Current advice on the across-the-day distribution of energy and carbohydrate
intakes in non-insulin-dependent diabetes (NIDD) is based on inadequate evidence.
We have addressed this by a comparison of an even as opposed to a main evening
meal pattern in 11 subjects with NIDD. Contributions of macronutrients to energy
intake were fat 29%, protein 20% and carbohydrate 51% with each meal pattern. The
peak glycaemic response in the morning was not as good as the response in the
evening (P<0.01), where an even energy and carbohydrate spread was used; this
contrasts with previous reports in healthy subjects where the morning response to
glucose is better than that later in the day. This difference between peak
morning and peak evening glycaemic response was not seen with a main evening
meal. There was a lower overall glycaemic response with a main evening meal
compared with an even meal pattern (P<0.01, by area comparison). The overall
insulin response was not significantly different between the two meal patterns,
although the sensitivity for insulin appeared better in the evening where there
was an evening main meal.
PMID- 24351143
TI - Conformal and highly luminescent monolayers of Alq3 prepared by gas-phase
molecular layer deposition.
AB - The gas-phase molecular layer deposition (MLD) of conformal and highly
luminescent monolayers of tris(8-hydroxyquinolinato)aluminum (Alq3) is reported.
The controlled formation of Alq3 monolayers is achieved for the first time by
functionalization of the substrate with amino groups, which serve as initial
docking sites for trimethyl aluminum (TMA) molecules binding datively to the
amine. Thereby, upon exposure to 8-hydroxyquinoline (8-HQ), the self-limiting
formation of highly luminescent Alq3 monolayers is afforded. The growth process
and monolayer formation were studied and verified by in situ quartz crystal
monitoring, optical emission and absorption spectroscopy, and X-ray photoelectron
spectroscopy. The nature of the MLD process provides an avenue to coat
arbitrarily shaped 3D surfaces and porous structures with high surface areas, as
demonstrated in this work for silica aerogels. The concept presented here paves
the way to highly sensitive luminescent sensors and dye-sensitized metal oxides
for future applications (e.g., in photocatalysis and solar cells).
PMID- 24351145
TI - Mouthwashes with hydrogen peroxide are carcinogenic, but are freely indicated on
the Internet: warn your patients!
AB - It all began in Ancient Egypt where people used to bleach their teeth with
antiseptic mouthwashes made of urea from human urine. Teeth harmony is promoted
by expression of feelings, communication, a real window of the brain and its
content! Tooth bleaching products are medicines, not cosmetics! Mouth washing
with hydrogen peroxide is an illogical and dangerous procedure! Hydrogen peroxide
must be used in one's mouth only when employed by a dentist who has been properly
instructed to protect the mucosa, preventing it from receiving these products.
How and for how long these products are going to be used require caution in order
to avoid or decrease any adverse effects on the tissues. Many websites instruct
people on how to purchase and prepare hydrogen peroxide so that it is used as an
antiseptic mouthwash and tooth bleaching agent. Some websites even refer to
dentists as "exploiters", accusing them of not instructing patients properly. In
this article, we aim at providing evidence and information upon which dentists
and assistants may base their thinking as well as their opinion and procedures
regarding "the indiscriminate and free use of hydrogen peroxide in the mouth, on
teeth and oral mucosa". Those websites, blogs and social network profiles
trespass the limits of public trust and should be immediately sued by the
government for committing a crime against public health.
PMID- 24351146
TI - Surface morphology changes of acrylic resins during finishing and polishing
phases.
AB - INTRODUCTION: The finishing and polishing phases are essential to improve
smoothness and shining on the surface of acrylic resins used to make removable
orthodontic appliances. A good surface finishing reduces roughness, which
facilitates hygiene, prevents staining and provides greater comfort to the
patients. OBJECTIVE: The aim of this paper was to analyze the changes on surface
morphology of acrylic resins during finishing and polishing phases. METHODS:
Thirty discs (10 mm in diameter and 5 mm in length) were made with acrylic resin
and randomly divided into ten groups. The control group did not receive any
treatment while the other groups received gradual finishing and polishing. The
last group received the entire finishing and polishing procedures. Surface
morphology was qualitatively analyzed through scanning electron microscopy and
quantitatively analyzed through a laser profilometer test. RESULTS: The acrylic
resin surfaces without treatment showed bubbles which were not observed in the
subsequent phases. Wearing out with multilaminated burs, finishing with wood
sandpaper and finishing with water sandpaper resulted in surfaces with decreasing
irregularities. The surfaces that were polished with pumice and with low abrasive
liquids showed high superficial smoothness. CONCLUSIONS: Highly smooth acrylic
resin surfaces can be obtained after mechanical finishing and polishing performed
with multilaminated burs, wood sandpaper, water sandpaper, pumice and low
abrasive liquids.
PMID- 24351147
TI - Clinical evaluation of dental alignment and leveling with three different types
of orthodontic wires.
AB - INTRODUCTION: A wide variety of orthodontic wires made of different alloys is
available to be used in orthodontic practice and may produce different clinical
responses during tooth movement. OBJECTIVE: This research evaluated the alignment
and leveling of lower dental arches after the use of three types of orthodontic
wires. METHODS: A sample of 36 patients was randomly divided into 3 groups:
stainless steel, multistranded steel and superelastic nickel-titanium, according
to the first leveling arches used. In order to observe differences in tooth
position and axial inclination of the lower incisors, all patients had lateral
cephalometric radiographs taken before the insertion of the first arches and 2
months later. The irregularity index and the curve of Spee were measured,
compared between groups and considered influential on the proclination of
incisors during the initial phase of alignment and leveling. The Reflex
microscope was used to measure the irregularity index, whereas the ANOVA analysis
of variance was used to verify differences between groups with regard to the
degree of dental alignment and leveling. RESULTS: There were significant
differences between groups only at T2 for the irregularity index. CONCLUSIONS:
The NiTi and multistranded steel wires showed greater aligning capacity when
compared with stainless steel wires.
PMID- 24351148
TI - Cone beam tomographic study of facial structures characteristics at rest and wide
smile, and their correlation with the facial types.
AB - OBJECTIVE: To determine the characteristics of facial soft tissues at rest and
wide smile, and their possible relation to the facial type. METHODS: We analyzed
a sample of forty-eight young female adults, aged between 19.10 and 40 years old,
with a mean age of 30.9 years, who had balanced profile and passive lip seal.
Cone beam computed tomographies were performed at rest and wide smile postures on
the entire sample which was divided into three groups according to individual
facial types. Soft tissue features analysis of the lips, nose, zygoma and chin
were done in sagittal, axial and frontal axis tomographic views. RESULTS: No
differences were observed in any of the facial type variables for the static
analysis of facial structures at both rest and wide smile postures. Dynamic
analysis showed that brachifacial types are more sensitive to movement,
presenting greater sagittal lip contraction. However, the lip movement produced
by this type of face results in a narrow smile, with smaller tooth exposure area
when compared with other facial types. CONCLUSIONS: Findings pointed out that the
position of the upper lip should be ahead of the lower lip, and the latter, ahead
of the pogonion. It was also found that the facial type does not impact the
positioning of these structures. Additionally, the use of cone beam computed
tomography may be a valuable method to study craniofacial features.
PMID- 24351149
TI - The influence of protective varnish on the integrity of orthodontic cements.
AB - OBJECTIVE: The aim of the present study was to assess the influence of saliva
contamination over the structural strength and integrity of conventional glass
ionomer cements used for cementing orthodontic bands in the absence and presence
of a surface-protecting varnish. METHODS: 48 samples were prepared by inserting 3
types of glass-ionomer cements into standardized metallic matrixes with 10 mm of
diameter and 2 mm of depth. The cements used were: Meron (VOCO), Ketac-Cem (3M
ESPE) and Vidrion C (DFL), all of which comprised groups A, B and C,
respectively. Subgroups A1, B1 and C1 comprised samples with no surface
protection, whereas subgroups A2, B2 and C2 comprised samples of which surface
was coated with Cavitine varnish (SS White), after cement manipulation and
application, in order to protect the cement applied. All samples were stored in
artificial saliva for 24 hours at 37 degrees C. A Vickers diamond micro-durometer
was used to produce indentations on the non-treated group (non-varnished) and the
treated group (varnished). RESULTS: Varnished materials had significantly higher
microhardness values in comparison to non-varnished materials. Ketac-Cem had the
highest microhardness value among the varnished materials. CONCLUSIONS: Varnish
application is necessary to preserve the cement and avoid enamel decalcification.
Glass-ionomer cements should be protected in order to fully keep their
properties, thus contributing to dental health during orthodontic treatment.
PMID- 24351150
TI - Comparative study on direct and indirect bracket bonding techniques regarding
time length and bracket detachment.
AB - OBJECTIVE: The aim of this study was to assess the time spent for direct (DBB -
direct bracket bonding) and indirect (IBB - indirect bracket bonding) bracket
bonding techniques. The time length of laboratorial (IBB) and clinical steps (DBB
and IBB) as well as the prevalence of loose bracket after a 24-week follow-up
were evaluated. METHODS: Seventeen patients (7 men and 10 women) with a mean age
of 21 years, requiring orthodontic treatment were selected for this study. A
total of 304 brackets was used (151 DBB and 153 IBB). The same bracket type and
bonding material were used in both groups. Data were submitted to statistical
analysis by Wilcoxon non-parametric test at 5% level of significance. RESULTS:
Considering the total time length, the IBB technique was more time-consuming than
the DBB (p < 0.001). However, considering only the clinical phase, the IBB took
less time than the DBB (p < 0.001). There was no significant difference (p =
0.910) for the time spent during laboratorial positioning of the brackets and
clinical session for IBB in comparison to the clinical procedure for DBB.
Additionally, no difference was found as for the prevalence of loose bracket
between both groups. CONCLUSIONS: The IBB can be suggested as a valid clinical
procedure since the clinical session was faster and the total time spent for
laboratorial positioning of the brackets and clinical procedure was similar to
that of DBB. In addition, both approaches resulted in similar frequency of loose
brackets.
PMID- 24351151
TI - Comparative cephalometric study of Class II malocclusion treatment with Pendulum
and Jones jig appliances followed by fixed corrective orthodontics.
AB - OBJECTIVE: The purpose of this study was to cephalometrically compare the
skeletal and dentoalveolar effects in the treatment of Class II malocclusion with
Pendulum and Jones jig appliances, followed by fixed corrective orthodontics, and
to compare such effects to a control group. METHODS: The sample was divided into
three groups. Group 1: 18 patients treated with Pendulum, Group 2: 25 patients
treated with Jones jig, and Group 3: 19 young subjects with untreated Class II
malocclusions and initial mean age of 12.88 years. The chi-square test was
applied to assess severity and gender distribution. Groups 1 and 2 were compared
to the control group by means of the one-way ANOVA and Tukey tests in order to
differentiate treatment changes from those occurred by craniofacial growth.
RESULTS: There were no significant changes among the three groups with regard to
the components of the maxilla and the mandible, maxillomandibular relationship,
cephalometric and tegumental pattern. Buccal tipping of mandibular incisors was
significantly greater in the experimental groups and increased mesial angulation
of the maxillary second molars was found in the Jones jig group. In the
experimental groups, dental relationship, overbite and overjet were corrected.
CONCLUSIONS: It can be stated that the distalization achieved its purpose of
correcting the Class II.
PMID- 24351152
TI - Brazilian orthodontists and the legal issues involving their professional
activity: A legal and behavioral proposal.
AB - OBJECTIVE: The aim of this study was to review the use of orthodontic records
(OTR's) by Brazilian orthodontists and propose a behavioral approach from a legal
point of view, drawing on their interpersonal relationship with their patients.
METHODS: A statistical cross-analysis was performed to compare five groups. A
sixth group was created comprising the intersection of the responses provided by
the five aforementioned groups. RESULTS: The results demonstrate that 42.2% of
orthodontists require initial and final records and keep orthodontic records
throughout their professional career; 13.9% duplicate the initial records and
consider patients as the lawful owners of these documents; 19.5% make use of a
medical history questionnaire, to be duly signed by all patients; 5.4%
acknowledge that the decision to undergo treatment is ultimately the patient's,
and, therefore, the alternative response "not perform the treatment" should be
included in the questionnaire; 24% recognize the importance of the Consumer
Protection Code (CPC), regard the provision of orthodontic services as an
obligation of means; and explain to the patient the risks involved in orthodontic
treatment. Among the 1,469 orthodontists researched, 0% simultaneously took into
account all aspects of this study. CONCLUSIONS: It was concluded that Brazilian
orthodontists adopt a mistaken legal, professional and behavioral attitude,
neglecting to build patient's orthodontic record with due care and in accordance
with the law, which makes them vulnerable to patient disputes, contentious or
otherwise.
PMID- 24351153
TI - Orthodontic movement of teeth with short root anomaly: Should it be avoided,
faced or ignored?
AB - INTRODUCTION: Short Root Anomaly (SRA) is an uncommon disease and a challenge for
orthodontic treatment as it tends to increase the risk of root resorption.
OBJECTIVE: Assess the current status of the diagnosis, etiology and orthodontic
management of teeth with SRA, and present case reports. METHODS: A literature
review was carried out in PubMed, SciELO, LILACS, Scopus and Web of Science
databases. RESULTS: A differential diagnosis of SRA should be conducted for teeth
with incomplete root formation, external apical root resorption, dentin dysplasia
type I and post dental trauma root hypoplasia. SRA is genetically determined and
orthodontic movement requires changes in clinical and radiographic management in
order to restrict damage. CONCLUSIONS: Orthodontic movement of teeth with SRA is
contraindicated in extreme cases, only. Caution at all stages could minimize
attachment loss and lead to long-term stability.
PMID- 24351154
TI - Procedures adopted by orthodontists for space closure and anchorage control.
AB - OBJECTIVE: The aim of this study was to identify the procedures adopted by
Brazilian orthodontists in the following situations: extraction space closure,
anchorage control in case of necessary anchorage for group A and frequency of
skeletal anchorage use, especially in the upper jaw. METHODS: A questionnaire was
sent to the e-mail address of all dentists registered in the Brazilian Federal
Council of Dentistry. RESULTS: The results showed that most Brazilian
orthodontists usually perform extraction space closure by means of sliding
mechanics. The use of palatal bar, inclusion of second molars in the archwire and
space closure performed in two phases are the most used techniques for anchorage
control in the upper jaw. The skeletal anchorage is referenced by 36.5% of
specialists as a routine practice for the upper arch anchorage. CONCLUSIONS:
There is a wide variety of procedures adopted by Brazilian orthodontists for
orthodontic space closure and anchorage control.
PMID- 24351155
TI - Prevalence of mesiodens in orthodontic patients with deciduous and mixed
dentition and its association with other dental anomalies.
AB - OBJECTIVE: To determine the prevalence of mesiodens in deciduous and mixed
dentitions and its association with other dental anomalies. MATERIAL AND METHODS:
Panoramic radiographs of 1,995 orthodontic patients were analyzed
retrospectively, obtaining a final sample of 30 patients with mesiodens. The
following aspects were analyzed: gender; number of mesiodens; proportion between
erupted and non-erupted mesiodens; initial position of the supernumerary tooth;
related complications; treatment plan accomplished; and associated dental
anomalies. The frequency of dental anomalies in the sample was compared to
reference values for the general population using the chi-square test, with a
significance level set at 5%. RESULTS: The prevalence of mesiodens was 1.5% more
common among males (1.5:1). Most of the mesiodens were non-erupted (75%) and in a
vertical position, facing the oral cavity. Extraction of the mesiodens was the
most common treatment. The main complications associated with mesiodens were:
delayed eruption of permanent incisors (34.28%) and midline diastema (28.57%).
From all the dental anomalies analyzed, only the prevalence of maxillary lateral
incisor agenesis was higher in comparison to the general population. CONCLUSIONS:
There was a low prevalence of mesiodens (1.5%) in deciduous and mixed dentition
and the condition was not associated with other dental anomalies, except for the
maxillary lateral incisor agenesis.
PMID- 24351156
TI - Applicability of Moyers analysis in mixed dentition: A systematic review.
AB - INTRODUCTION: Moyers analysis is widely used for analyzing mixed dentition,
however, the accuracy of its theoretical probability tables has been recently
questioned. Taking into consideration the fact the mixed dentition analysis is of
paramount importance to precisely determine the space needed for alignment of
canines and premolars, this research aimed at objectively assessing in the
literature such an important step for orthodontic diagnosis. METHODS: A
computerized search involving articles published on PubMed and Lilacs between
1990 and September, 2011 was conducted in accordance with the method described in
the Cochrane 5.1.0 handbook. RESULTS: The research resulted in a sample composed
of 629 articles. The inclusion criteria were: Articles using the Moyers analysis
with a sample greater or equal to 40 patients. Conversely, the exclusion criteria
were: Dental casts of patients with syndromes or oral cleft, researches conducted
with a literature review, only, or clinical case reports and researches conducted
before 1990. For this systematic review, 19 articles were selected. CONCLUSIONS:
Based on the literature available, we can conclude that Moyers mixed dentition
analysis must be carefully used, since the majority of the articles analyzed
showed that the probability of 75% was not as accurate as expected, leading to
the need of adapting the probability levels depending on the study population.
PMID- 24351157
TI - Assessment of first molars sagittal and rotational position in Class II, division
1 malocclusion.
AB - OBJECTIVE: This study assessed the anterior-posterior positioning of the upper
and lower first molars, and the degree of rotation of the upper first molars in
individuals with Class II, division 1, malocclusion. METHODS: Asymmetry I, an
accurate device, was used to assess sixty sets of dental casts from 27 females
and 33 males, aged between 12 and 21 years old, with bilateral Class II, division
1. The sagittal position of the molars was determined by positioning the casts
onto the device, considering the midpalatal suture as a symmetry reference, and
then measuring the distance between the mesial marginal ridge of the most distal
molar and the mesial marginal ridge of its counterpart. With regard to the degree
of rotation of the upper molar, the distance between landmarks on the mesial
marginal ridge was measured. Chi-square test with a 5% significance level was
used to verify the variation in molars position. Student's t test at 5%
significance was used for statistical analysis. RESULTS: A great number of lower
molars mesially positioned was registered, and the comparison between the right
and left sides also demonstrated a higher number of mesially positioned molars on
the right side of both arches. The average rotation of the molars was found to be
0.76 mm and 0.93 mm for the right and left sides, respectively. CONCLUSIONS: No
statistically significant difference was detected between the mean values of
molars mesialization regardless of the side and arch. Molars rotation, measured
in millimeters, represented 1/4 of Class II.
PMID- 24351158
TI - Prototype of a new tip developed to be coupled to dental light-curing units for
optimizing bonding of orthodontic brackets and accessories.
AB - OBJECTIVE: Development of a new device to be coupled to light-curing units for
bonding orthodontic brackets and accessories, and test its efficacy in an in
vitro mechanical trial. The inner surface of the device is mirrored and is based
on physical concepts of light refraction and reflection. The main advantage of
such device is the reduced clinical time needed for bonding and the low
possibility of contamination during the process. METHODS: One hundred and twenty
specimens were used for testing the shear bond strength of brackets bonded with
the device. The Adhesive Remnant Index (ARI) was also determined. The sample was
divided into 2 groups. In group 1 a halogen light-curing unit was used while in
group 2 a led light-curing unit was used. Each group was then subdivided. In
subgroups H1 and L1, a conventional light guide rod was used while in subgroups
H2 and L2 bonding was performed with the mirrored device coupled to the tip of
the guide light rod. RESULTS: The values obtained for the shear bond strength and
the ARI in the subgroups were compared. Results showed that there was no
statistically significant difference for the shear strength (p > 0.05) and the
ARI (p > 0.05) between the subgroups. CONCLUSIONS: The tests of mechanical trials
and the ARI analysis showed that the new device fulfilled the requirements for
bonding orthodontic accessories, and that the time for bonding was reduced to
half, being necessary only one light exposure.
PMID- 24351160
TI - Flexural strength of mini-implants developed for Herbst appliance skeletal
anchorage. A study in Minipigs br1 cadavers.
AB - OBJECTIVE: The present study was designed to verify if mini-implant prototypes
(MIP) developed for Herbst appliance anchorage are capable of withstanding
orthopedic forces, and to determine whether the flexural strength of these MIP
varies depending on the site of insertion (maxilla and mandible). METHODS:
Thirteen MIP were inserted in three minipig cadavers (six in the maxilla and
seven in the mandible). The specimens were prepared and submitted to mechanical
testing. The mean and standard deviation were calculated for each region. A two
way Student's t test was used to compare the strength between the sites. A one
way Student's t test was performed to test the hypothesis. Orthopedic forces
above 1.0 kgf were considered. RESULTS: The MIP supported flexural strength
higher than 1.0 kgf (13.8 +/- 2.3 Kg, in the posterior region of the maxilla and
20.5 +/- 5.2 Kg in the anterior region of the mandible) with a significantly
lower flexural strength in the anterior region of the mandible (p < 0.05).
CONCLUSIONS: The MIP are capable of withstanding orthopedic forces, and are more
resistant in the anterior region of the mandible than in the posterior region of
the maxilla in Minipigs br1 cadavers.
PMID- 24351159
TI - Pain, masticatory performance and swallowing threshold in orthodontic patients.
AB - OBJECTIVE: The aim of this study was to assess pain, masticatory performance and
swallowing threshold of patients undergoing orthodontic treatment. METHODS: Ten
patients of both genders (mean age of 17.25 +/- 5.21 years), with complete
permanent dentition, who underwent orthodontic treatment with fixed appliances
were evaluated. The masticatory performance and the swallowing threshold were
assessed by patient's individual capacity of fragmenting an artificial test food
(Optocal) which was chewed and had the resulting particles processed by a
standardized sieving method, presenting the median particle size (MPS) of crushed
units. The intensity of pain / discomfort during chewing was evaluated by means
of a visual analog scale. All tests were performed at the following times: T0 -
before activating the orthodontic appliance; T1 - 24 hours after activation, and
T2 - 30 days after activation. RESULTS: The results showed a significant increase
in pain at T1 (T0 = 0.60 +/- 0.70 mm; T1 = 66.2 +/- 34.5 mm), returning to
baseline values at T2 (3.20 +/- 3.82 mm). Masticatory performance was also
reduced in T1 (MPS = 10.15 +/- 1.1 mm2) in comparison to T0 (MPS 7.01 +/- 2.9
mm2) and T2 (MPS 6.76 +/- 1.3 mm2). However, particle size was not affected in
the swallowing threshold test (T0 = 5.47 +/- 2.37 mm2; T1 = 6.19 +/- 2.05 mm2; T2
= 5.94 +/- 2.36 mm2). CONCLUSIONS: The orthodontic appliances did not interfere
in the size of the particles that would be swallowed, even in the presence of
pain.
PMID- 24351161
TI - Treatment of dental and skeletal bimaxillary protrusion in patient with Angle
Class I malocclusion.
AB - In the orthodontic clinic, skeletal and dental bimaxillary protrusion is
presented frequently as one of the factors leading patients to seek orthodontic
treatment, mainly due to the esthetic involvement it has. The patient of this
article illustrates this situation, being deeply uncomfortable with her esthetic
appearance, due to the excessive upper incisors exposure and problems with lip
sealing. This case was presented to the Brazilian Board of Orthodontics and
Facial Orthopedics (BBO), as part of the requisites to become a BBO Diplomate.
PMID- 24351162
TI - Reconstruction of alveolar cleft with allogenous bone graft: Clinical
considerations.
AB - INTRODUCTION: Secondary bone grafting consists in a routine procedure on the
treatment of patients with alveolar cleft. Usually, it is performed by the end of
the mixed dentition, when the permanent canine is erupting, with autogenous
cancellous bone from the iliac crest. OBJECTIVE: The present article discusses
the alternative of autogenous bone grafting with allogeneic bone, obtained from
human bone bank, illustrating the result with the report of a clinical case of
left unilateral alveolar cleft.
PMID- 24351163
TI - Combined chelation therapy with deferoxamine and deferiprone in beta-thalassemia
major: compliance and opinions of young thalassemic patients.
AB - Treatment of beta-thalassemia major (beta-TM) includes regular blood transfusions
and iron chelation with subcutaneous injection of deferoxamine (DFO). During the
last decade, a new chelation agent, deferiprone (L1), was introduced. The purpose
of our study was to determine the level of awareness/education regarding
chelation therapy, the degree of compliance to this therapy and their views of L1
in patients with beta-TM. A relevant questionnaire was administered to 36
patients (12-26 years old) who were on combination chelation therapy with both
DFO and L1. The majority of patients was well aware/educated about chelation
therapy (76.6%), was compliant with this therapy (74.4%) and had a positive view
towards oral chelation (86.0%). In conclusion, most patients with beta-TM who
were on combination chelation therapy with DFO and L1 were satisfied with this
treatment and this results in high compliance rates.
PMID- 24351164
TI - The IJHPR publishes its 100th article, and other momentous milestones.
AB - The Israel Journal of Health Policy Research (IJHPR) was launched in January 2012
and it is now publishing its 100th article. It was accepted into PubMed after
only six months of publication and it has now also been accepted by Thomson
Reuters for inclusion in the Web of Science as well as the Social Science
Citation Index. It is rare for a new journal to reach these milestones at such an
early stage in its development.One of the key factors in the journal's acceptance
into these prestigious databases has been its unique national/international
approach - exploring both what Israel can learn from health systems in other
countries and what other countries can learn from Israeli health care. Another
key factor has been its ability to attract high quality contributions from
virtually all of the Israeli universities and research centers involved in health
policy. A third important factor has been the journal's ability to engage leading
international scholars as contributors and/or editorial board members.
PMID- 24351165
TI - Rotating phenyl rings as a guest-dependent switch in two-dimensional metal
organic frameworks.
AB - A semirigid bis(1,2,4-triazole) ligand binds in a syn conformation between
copper(I) chains to form a series of two-dimensional metal-organic frameworks
that display a topology of fused one-dimensional metal-organic nanotubes. These
anisotropic frameworks undergo two different transformations in the solid state
as a function of solvation. The 2D sheet layers can expand or contract, or, more
remarkably, the phenyl rings can rotate between two distinct positions. Rotation
of the phenyl rings allows for the adjustment of the tube size, depending on the
guest molecules present. This "gate" effect along the 1D tubes has been
characterized through single-crystal X-ray diffraction. The transformations can
also be followed by powder X-ray diffraction (PXRD) and solid-state (13)C cross
polarization magic-angle-spinning (CP-MAS) NMR. Whereas PXRD cannot differentiate
between transformations, solid-state (13)C CP-MAS NMR can be employed to directly
monitor phenyl rotation as a function of solvation, suggesting that this
spectroscopic method is a powerful approach for monitoring breathing in this
novel class of frameworks. Finally, simulations show that rotation of the phenyl
ring from a parallel orientation to a perpendicular orientation occurs at the
cost of framework-framework energy and that this energetic cost is offset by
stronger framework-solvent interactions.
PMID- 24351166
TI - "Forgetting to remember" in Huntington's disease: a study of laboratory, semi
naturalistic, and self-perceptions of prospective memory.
AB - Prospective memory (PM) is dependent on executive processes known to be impaired
in Huntington's disease (HD); however, no study to the authors' knowledge has
investigated PM in this group. We examined performance-based, semi-naturalistic,
and self-reported PM in 20 individuals diagnosed with mild-moderate HD and 20
demographically similar controls. Relative to controls, HD participants
demonstrated significantly lower scores in time-based PM, event-based PM (at a
trend level), and the semi-naturalistic PM trial, all of which were marked by
omission errors. HD participants demonstrated comparable recognition memory for
the PM intentions relative to controls. HD and control participants also showed
comparable scores in self-reported PM complaints. The results suggest that HD is
associated with deficits in the strategic aspects of PM. HD-associated PM
deficits also are evident in real-world situations, which may relate to an
apparent meta-memory deficit for PM functioning as indicated by HD participants'
overestimation of their PM performance on self-report.
PMID- 24351167
TI - Artificial pancreas goes outpatient: a new diabetes ecosystem.
PMID- 24351168
TI - DiAs user interface: a patient-centric interface for mobile artificial pancreas
systems.
AB - BACKGROUND: Recent in-hospital studies of artificial pancreas (AP) systems have
shown promising results in improving glycemic control in patients with type 1
diabetes mellitus. The next logical step in AP development is to conduct
transitional outpatient clinical trials with a mobile system that is controlled
by the patient. In this article, we present the user interface (UI) of the
Diabetes Assistant (DiAs), an experimental smartphone-based mobile AP system, and
describe the reactions of a round of focus groups to the UI. This work is an
initial inquiry involving a relatively small number of potential users, many of
whom had never seen an AP system before, and the results should be understood in
that light. METHODS: We began by considering how the UI of an AP system could be
designed to make use of the familiar touch-based graphical UI of a consumer
smartphone. After developing a working prototype UI, we enlisted a human factors
specialist to perform a heuristic expert analysis. Next we conducted a formative
evaluation of the UI through a series of three focus groups with N = 13 potential
end users as participants. The UI was modified based upon the results of these
studies, and the resulting DiAs system was used in transitional outpatient AP
studies of adults in the United States and Europe. RESULTS: The DiAs UI was
modified based on focus group feedback from potential users. The DiAs was
subsequently used in JDRF- and AP@Home-sponsored transitional outpatient AP
studies in the United States and Europe by 40 subjects for 2400 h with no adverse
events. CONCLUSIONS: Adult patients with type 1 diabetes mellitus are able to
control an AP system successfully using a patient-centric UI on a commercial
smartphone in a transitional outpatient environment.
PMID- 24351169
TI - DiAs web monitoring: a real-time remote monitoring system designed for artificial
pancreas outpatient trials.
AB - BACKGROUND: Developments in an artificial pancreas (AP) for patients with type 1
diabetes have allowed a move toward performing outpatient clinical trials. "Home
like" environment implies specific protocol and system adaptations among which
the introduction of remote monitoring is meaningful. We present a novel tool
allowing multiple patients to monitor AP use in home-like settings. METHODS: We
investigated existing systems, performed interviews of experienced clinical
teams, listed required features, and drew several mockups of the user interface.
The resulting application was tested on the bench before it was used in three
outpatient studies representing 3480 h of remote monitoring. RESULTS: Our tool,
called DiAs Web Monitoring (DWM), is a web-based application that ensures
reception, storage, and display of data sent by AP systems. Continuous glucose
monitoring (CGM) and insulin delivery data are presented in a colored chart to
facilitate reading and interpretation. Several subjects can be monitored
simultaneously on the same screen, and alerts are triggered to help detect events
such as hypoglycemia or CGM failures. In the third trial, DWM received
approximately 460 data per subject per hour: 77% for log messages, 5% for CGM
data. More than 97% of transmissions were achieved in less than 5 min.
CONCLUSIONS: Transition from a hospital setting to home-like conditions requires
specific AP supervision to which remote monitoring systems can contribute
valuably. DiAs Web Monitoring worked properly when tested in our outpatient
studies. It could facilitate subject monitoring and even accelerate medical and
technical assessment of the AP. It should now be adapted for long-term studies
with an enhanced notification feature.
PMID- 24351170
TI - Dexcom G4AP: an advanced continuous glucose monitor for the artificial pancreas.
AB - Input from continuous glucose monitors (CGMs) is a critical component of
artificial pancreas (AP) systems, but CGM performance issues continue to limit
progress in AP research. While G4 PLATINUM has been integrated into AP systems
around the world and used in many successful AP controller feasibility studies,
this system was designed to address the needs of ambulatory CGM users as an
adjunctive use system. Dexcom and the University of Padova have developed an
advanced CGM, called G4AP, to specifically address the heightened performance
requirements for future AP studies. The G4AP employs the same sensor and
transmitter as the G4 PLATINUM but contains updated denoising and calibration
algorithms for improved accuracy and reliability. These algorithms were applied
to raw data from an existing G4 PLATINUM clinical study using a simulated
prospective procedure. The results show that mean absolute relative difference
(MARD) compared with venous plasma glucose was improved from 13.2% with the G4
PLATINUM to 11.7% with the G4AP. Accuracy improvements were seen over all days of
sensor wear and across the plasma glucose range (40-400 mg/dl). The greatest
improvements occurred in the low glucose range (40-80 mg/dl), in euglycemia (80
120 mg/dl), and on the first day of sensor use. The percentage of sensors with a
MARD <15% increased from 69% to 80%. Metrics proposed by the AP research
community for addressing specific AP requirements were also computed. The G4AP
consistently exhibited improved sensor performance compared with the G4 PLATINUM.
These improvements are expected to enable further advances in AP research.
PMID- 24351171
TI - Periodic-zone model predictive control for diurnal closed-loop operation of an
artificial pancreas.
AB - BACKGROUND: The objective of this research is an artificial pancreas (AP) that
performs automatic regulation of blood glucose levels in people with type 1
diabetes mellitus. This article describes a control strategy that performs
algorithmic insulin dosing for maintaining safe blood glucose levels over
prolonged, overnight periods of time and furthermore was designed with
outpatient, multiday deployment in mind. Of particular concern is the prevention
of nocturnal hypoglycemia, because during sleep, subjects cannot monitor
themselves and may not respond to alarms. An AP intended for prolonged and
unsupervised outpatient deployment must strategically reduce the risk of
hypoglycemia during times of sleep, without requiring user interaction. METHODS:
A diurnal insulin delivery strategy based on predictive control methods is
proposed. The so-called "periodic-zone model predictive control" (PZMPC) strategy
employs periodically time-dependent blood glucose output target zones and
furthermore enforces periodically time-dependent insulin input constraints to
modulate its behavior based on the time of day. RESULTS: The proposed strategy
was evaluated through an extensive simulation-based study and a preliminary
clinical trial. Results indicate that the proposed method delivers insulin more
conservatively during nighttime than during daytime while maintaining safe blood
glucose levels at all times. In clinical trials, the proposed strategy delivered
77% of the amount of insulin delivered by a time-invariant control strategy;
specifically, it delivered on average 1.23 U below, compared with 0.31 U above,
the nominal basal rate overnight while maintaining comparable, and safe, blood
glucose values. CONCLUSIONS: The proposed PZMPC algorithm strategically prevents
nocturnal hypoglycemia and is considered a significant step toward deploying APs
into outpatient environments for extended periods of time in full closed-loop
operation.
PMID- 24351172
TI - In silico optimization of basal insulin infusion rate during exercise:
implication for artificial pancreas.
AB - BACKGROUND: Several clinical trials have been performed to assess safety and
efficacy of closed-loop control. Some included physical activity (PA), with the
goal of challenging the control algorithms with a rapid change in insulin
sensitivity while reducing the risk of hypoglycemia. However, the question
remains as to the necessity to inform the control algorithm on the imminent PA.
The aim here is to assess in silico (i) if it is necessary to announce upcoming
PA and (ii) if this is the case, what is the safest strategy of basal insulin
reduction in the context of the closed-loop control. METHODS: We modified the
University of Virginia/Padova type 1 diabetes simulator to incorporate the effect
of PA based on a study in healthy subjects that demonstrated an almost doubling
of insulin sensitivity during PA versus rest. Two in silico experiments,
including a PA session, have been simulated on the virtual adult population: one
in the absence of and one with different degrees of reductions and durations of
basal insulin infusion rates. RESULTS: Most in silico subjects experienced
hypoglycemia in the absence of basal insulin adjustment. We show that, in the
absence of patient-specific information, a safe and effective strategy is to
reduce basal insulin by 50% starting 90 min before exercise and by 30% during
exercise. CONCLUSIONS: Our results suggest that control algorithms could benefit
by knowing an upcoming PA. Ideally, the control algorithm should be informed
about the patient-specific basal insulin reduction pattern. An alternative
strategy that has been proposed here has been deemed safe and effective in in
silico experiments.
PMID- 24351173
TI - Artificial pancreas: model predictive control design from clinical experience.
AB - BACKGROUND: The objective of this research is to develop a new artificial
pancreas that takes into account the experience accumulated during more than 5000
h of closed-loop control in several clinical research centers. The main objective
is to reduce the mean glucose value without exacerbating hypo phenomena.
Controller design and in silico testing were performed on a new virtual
population of the University of Virginia/Padova simulator. METHODS: A new sensor
model was developed based on the Comparison of Two Artificial Pancreas Systems
for Closed-Loop Blood Glucose Control versus Open-Loop Control in Patients with
Type 1 Diabetes trial AP@home data. The Kalman filter incorporated in the
controller has been tuned using plasma and pump insulin as well as plasma and
continuous glucose monitoring measures collected in clinical research centers.
New constraints describing clinical knowledge not incorporated in the simulator
but very critical in real patients (e.g., pump shutoff) have been introduced. The
proposed model predictive control (MPC) is characterized by a low computational
burden and memory requirements, and it is ready for an embedded implementation.
RESULTS: The new MPC was tested with an intensive simulation study on the
University of Virginia/Padova simulator equipped with a new virtual population.
It was also used in some preliminary outpatient pilot trials. The obtained
results are very promising in terms of mean glucose and number of patients in the
critical zone of the control variability grid analysis. CONCLUSIONS: The proposed
MPC improves on the performance of a previous controller already tested in
several experiments in the AP@home and JDRF projects. This algorithm complemented
with a safety supervision module is a significant step toward deploying
artificial pancreases into outpatient environments for extended periods of time.
PMID- 24351174
TI - Accuracy of a first-generation intravenous blood glucose monitoring system in
subjects with diabetes mellitus: a multicenter study.
AB - BACKGROUND: Hyperglycemia and hypoglycemia in hospitalized patients have been
associated with increased morbidity and mortality. Improvements in glucose
monitoring technology may be helpful in the clinical management of critically ill
patients with abnormal glucose levels. A first-generation intravenous blood
glucose monitoring (IVBG) system was developed to facilitate glycemic control
therapy in hospitalized patients. A nonrandomized, single-arm, multicenter study
was performed to evaluate the safety and accuracy of the IVBG system in insulin
treated subjects with diabetes mellitus. METHODS: The IVBG system is a bedside
monitor that automatically measures venous blood glucose (BG) concentration. In
this study, BG was measured every 7.5 min by the IVBG system. Reference samples
[venous blood samples measured on the Yellow Springs Instruments (YSI) glucose
analyzer] were drawn every 15 min during inpatient studies on days 1, 2, and 3.
Fifty insulin-treated healthy volunteers with diabetes were studied, and a
maximum of 72 reference samples were collected. Effectiveness was primarily
evaluated by assessing the proportion of IVBG BG measurements within the 15 mg/dl
or 20% criterion [15 mg/dl (for YSI <75 mg/dl) or 20% (for YSI >=75 mg/dl)]
compared with YSI. Adverse events and adverse device effects were evaluated.
RESULTS: A total of 95% of all IVBG values were within the 15 mg/dl or 20%
criterion. The IVBG system BG measurement showed significant linear relationship
with the laboratory YSI standard. Catheter insertion site irritation was mild and
infrequent. No serious adverse events were reported. A total of 33% of the
sensors were replaced during the 3-day use due to problematic IV lines or
sensor/system errors. CONCLUSIONS: This clinical performance evaluation
demonstrates that the IVBG system provides accurate and safe continuous BG
measurements in healthy insulin-treated patients with diabetes.
PMID- 24351175
TI - Complexity of continuous glucose monitoring data in critically ill patients:
continuous glucose monitoring devices, sensor locations, and detrended
fluctuation analysis methods.
AB - BACKGROUND: Critically ill patients often experience high levels of insulin
resistance and stress-induced hyperglycemia, which may negatively impact
outcomes. However, evidence surrounding the causes of negative outcomes remains
inconclusive. Continuous glucose monitoring (CGM) devices allow researchers to
investigate glucose complexity, using detrended fluctuation analysis (DFA), to
determine whether it is associated with negative outcomes. The aim of this study
was to investigate the effects of CGM device type/calibration and CGM sensor
location on results from DFA. METHODS: This study uses CGM data from critically
ill patients who were each monitored concurrently using Medtronic iPro2s on the
thigh and abdomen and a Medtronic Guardian REAL-Time on the abdomen. This allowed
interdevice/calibration type and intersensor site variation to be assessed.
Detrended fluctuation analysis is a technique that has previously been used to
determine the complexity of CGM data in critically ill patients. Two variants of
DFA, monofractal and multifractal, were used to assess the complexity of sensor
glucose data as well as the precalibration raw sensor current. Monofractal DFA
produces a scaling exponent (H), where H is inversely related to complexity. The
results of multifractal DFA are presented graphically by the multifractal
spectrum. RESULTS: From the 10 patients recruited, 26 CGM devices produced data
suitable for analysis. The values of H from abdominal iPro2 data were 0.10 (0.03
0.20) higher than those from Guardian REAL-Time data, indicating consistently
lower complexities in iPro2 data. However, repeating the analysis on the raw
sensor current showed little or no difference in complexity. Sensor site had
little effect on the scaling exponents in this data set. Finally, multifractal
DFA revealed no significant associations between the multifractal spectrums and
CGM device type/calibration or sensor location. CONCLUSIONS: Monofractal DFA
results are dependent on the device/calibration used to obtain CGM data, but
sensor location has little impact. Future studies of glucose complexity should
consider the findings presented here when designing their investigations.
PMID- 24351176
TI - Pharmacokinetics of insulin aspart and glucagon in type 1 diabetes during closed
loop operation.
AB - BACKGROUND: We assessed the pharmacokinetics of subcutaneous insulin aspart and
glucagon during closed-loop operation and their relationship with body
composition variables. METHODS: We retrospectively analyzed data collected from
closed-loop experiments in 15 type 1 diabetes patients (age 47.1 +/- 12.3 years,
body mass index 25.9 +/- 4.6 kg/m2, glycated hemoglobin 7.9% +/- 0.7%). Patients
received an evening meal accompanied with prandial insulin bolus and stayed in
the clinical facility until the next morning. Glucose levels were regulated by
dual-hormone closed-loop delivery. Insulin and glucagon were delivered using two
subcutaneous infusion pumps installed on the abdominal wall. Plasma insulin and
glucagon were measured every 10-30 min. Percentage of body fat, percentage of fat
in the abdominal area, and mass of abdominal fat were measured by dual X-ray
absorptiometry. RESULTS: A pharmacokinetic model estimated time-to-peak plasma
concentrations [t(max) insulin 51 (19) min, t(max) glucagon 19 (4) min, mean
(standard deviation)], metabolic clearance rate [MCR insulin 0.019 (0.015-0.026)
liter/kg/min, MCR glucagon 0.012 (0.010-0.014) liter/kg/min, median
(interquartile range)], and the background plasma concentrations [I(b) insulin
10.2 (6.3-15.2) mU/liter, I(b) glucagon 50 (45-56) pg/ml, median (interquartile
range)]. t(max) correlated positively between insulin and glucagon (r = 0.7; p =
.007) while MCR correlated negatively (r = -0.7; p = .015). In this small sample
size, t(max), MCR, and I(b) of insulin and glucagon did not correlate with
percentage of body fat, percentage of fat in the abdominal area, or total mass of
abdominal fat. CONCLUSIONS: Insulin and glucagon pharmacokinetics might be
related during closed-loop operation. Our data suggest that slower absorption of
insulin is associated with slower absorption of glucagon. Body composition does
not seem to influence insulin and glucagon pharmacokinetics.
PMID- 24351177
TI - Influence of partial pressure of oxygen in blood samples on measurement
performance in glucose-oxidase-based systems for self-monitoring of blood
glucose.
AB - BACKGROUND: Partial pressure of oxygen (pO2) in blood samples can affect blood
glucose (BG) measurements, particularly in systems that employ the glucose
oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the
impact of different pO2 values on the performance of five GOx systems and one
glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the
manufacturers to be sensitive to increased blood oxygen content, while the other
three GOx systems are not. METHODS: Aliquots of 20 venous samples were adjusted
to the following pO2 values: <45, ~70, and >=150 mmHg. For each system, five
consecutive measurements on each sample aliquot were performed using the same
test strip lot. Relative differences between the mean BG results at pO2 ~70 mmHg,
which is considered to be similar to pO2 in capillary blood samples, and the mean
BG result at pO2 <45 and >=150 mmHg were calculated. RESULTS: For all tested GOx
systems, mean relative differences in the BG measurement results were between
6.1% and 22.6% at pO2 <45 mmHg and between -7.9% and -14.9% at pO2 >=150 mmHg.
For both pO2 levels, relative differences of all tested GOx systems were
significant (p < .0001). The GDH system showed mean relative differences of -1.0%
and -0.4% at pO2 values <45 and >=150 mmHg, respectively, which were not
significant. CONCLUSIONS: These data suggest that capillary blood pO2 variations
lead to clinically relevant BG measurement deviations in GOx systems, even in GOx
systems that are not labeled as being oxygen sensitive.
PMID- 24351178
TI - Evaluation of the effects of insufficient blood volume samples on the performance
of blood glucose self-test meters.
AB - BACKGROUND: Accuracy of blood glucose readings is (among other things) dependent
on the test strip being completely filled with sufficient sample volume. The
devices are supposed to display an error message in case of incomplete filling.
This laboratory study was performed to test the performance of 31 commercially
available devices in case of incomplete strip filling. METHODS: Samples with two
different glucose levels (60-90 and 300-350 mg/dl) were used to generate three
different sample volumes: 0.20 ul (too low volume for any device), 0.32 ul
(borderline volume), and 1.20 ul (low but supposedly sufficient volume for all
devices). After a point-of-care capillary reference measurement (StatStrip,
NovaBiomedical), the meter strip was filled (6x) with the respective volume, and
the response of the meters (two devices) was documented (72 determinations/meter
type). Correct response was defined as either an error message indicating
incomplete filling or a correct reading (+/-20% compared with reference reading).
RESULTS: Only five meters showed 100% correct responses [BGStar and iBGStar (both
Sanofi), ACCU-CHEK Compact+ and ACCU-CHEK Mobile (both Roche Diagnostics),
OneTouch Verio (LifeScan)]. The majority of the meters (17) had up to 10%
incorrect reactions [predominantly incorrect readings with sufficient volume;
Precision Xceed and Xtra, FreeStyle Lite, and Freedom Lite (all Abbott);
GlucoCard+ and GlucoMen GM (both Menarini); Contour, Contour USB, and Breeze2
(all Bayer); OneTouch Ultra Easy, Ultra 2, and Ultra Smart (all LifeScan);
Wellion Dialog and Premium (both MedTrust); FineTouch (Terumo); ACCU-CHEK Aviva
(Roche); and GlucoTalk (Axis-Shield)]. Ten percent to 20% incorrect reactions
were seen with OneTouch Vita (LifeScan), ACCU-CHEK Aviva Nano (Roche), OmniTest+
(BBraun), and AlphaChek+ (Berger Med). More than 20% incorrect reactions were
obtained with Pura (Ypsomed), GlucoCard Meter and GlucoMen LX (both Menarini),
Elite (Bayer), and MediTouch (Medisana). CONCLUSIONS: In summary, partial and
incomplete blood filling of glucose meter strips is often associated with
inaccurate reading. These findings underline the importance of appropriate
patient education on this aspect of blood glucose self-monitoring.
PMID- 24351179
TI - Blood glucose meters employing dynamic electrochemistry are stable against
hematocrit interference in a laboratory setting.
AB - BACKGROUND: Hematocrit (HCT) is known to be a confounding factor that interferes
with many blood glucose (BG) measurement technologies, resulting in wrong
readings. Dynamic electrochemistry has been identified as one possible way to
correct for these potential deviations. The purpose of this laboratory
investigation was to assess the HCT stability of four BG meters known to employ
dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix;
Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock,
Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott
Medisense). METHODS: Venous heparinized blood was immediately aliquoted after
draw and manipulated to contain three different BG concentrations (60-90, 130
160, and 280-320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and
60%). After careful oxygenation to normal blood oxygen pressure, each of the
resulting 15 different samples was measured six times with three devices and
three strip lots of each meter. The YSI Stat 2300 served as laboratory reference
method. Stability to HCT influence was assumed when less than 10% difference
occurred between the highest and lowest mean glucose deviations in relation to
HCT concentrations [hematocrit interference factor (HIF)]. RESULTS: Five of the
investigated self-test meters showed a stable performance with the different HCT
levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense
Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other
meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%).
CONCLUSIONS: In this study, meters employing dynamic electrochemistry, as used in
the BGStar and iBGStar devices, were shown to correct for potential HCT influence
on the meter results. Dynamic electrochemistry appears to be an effective way to
handle this interfering condition.
PMID- 24351180
TI - Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in
long-term continuous glucose monitoring in vivo.
AB - BACKGROUND: Glucose-sensor-induced tissue reactions (e.g., inflammation and wound
healing) are known to negatively impact sensor function in vivo. The roles of
cytokine networks in controlling these tissue reactions (i.e., sensor biofouling)
is not understood. In the present study, we investigated the role of interleukin
1 receptor antagonist (IL-1Ra), a key anti-inflammatory antagonist of the
proinflammatory interleukin-1 cytokines [i.e. interleukin-1 (IL-1) alpha and IL-1
beta] in controlling continuous glucose monitoring (CGM). METHODS: To investigate
the role of IL-1Ra in long-term CGM in vivo, we compared CGM in transgenic mice
that overexpress IL-1Ra [interleukin-1 receptor antagonist overexpresser (IL
1Ra~OE), B6.Cg-Tg(IL1rn)1Dih/J] or are deficient in IL-1Ra [interleukin-1
receptor antagonist knockout (IL-1Ra~KO), B6.129S-IL1rn(tm1Dih)/J] with mice that
have normal levels of IL-1Ra (C57BL/6) over a 28-day time period. RESULTS: Mean
absolute relative difference (MARD) analysis of CGM results among the mice of
varying IL-1Ra levels demonstrated that during the first 21 days, IL-1~KO mice
had the greatest tissue inflammation and the poorest sensor performance (i.e.,
higher MARD values) when compared with normal or IL-1Ra~OE mice. By 28 days post
sensor implantation, the inflammatory reactions had subsided and were replaced by
varying degrees of fibrosis. CONCLUSIONS: These data support our hypothesis on
the importance of the IL-1 family of agonists and antagonists in controlling
tissue reactions and sensor function in vivo. These data also suggest that local
delivery of IL-1Ra genes or recombinant proteins (anakinra) or other IL-1
antagonists such as antibodies or soluble IL-1 receptors would suppress sensor
induced tissue reactions and likely enhance glucose sensor function by inhibiting
inflammation and wound healing at sensor implantation sites.
PMID- 24351181
TI - Predicting glucose sensor behavior in blood using transport modeling: relative
impacts of protein biofouling and cellular metabolic effects.
AB - BACKGROUND: Tissue response to indwelling glucose sensors remains a confounding
barrier to clinical application. While the effects of fully formed capsular
tissue on sensor response have been studied, little has been done to understand
how tissue interactions occurring before capsule formation hinder sensor
performance. Upon insertion in subcutaneous tissue, the sensor is initially
exposed to blood, blood borne constituents, and interstitial fluid. Using human
whole blood as a simple ex vivo experimental system, the effects of protein
accumulation at the sensor surface (biofouling effects) and cellular consumption
of glucose in both the biofouling layer and in the bulk (metabolic effects) on
sensor response were assessed. METHODS: Medtronic MiniMed SofSensor glucose
sensors were incubated in whole blood, plasma-diluted whole blood, and cell-free
platelet-poor plasma (PPP) to analyze the impact of different blood constituents
on sensor function. Experimental conditions were then simulated using MATLAB to
predict the relative impacts of biofouling and metabolic effects on the observed
sensor responses. RESULTS: Protein biofouling in PPP in both the experiments and
the simulations was found to have no interfering effect upon sensor response.
Experimental results obtained with whole and dilute blood showed that the sensor
response was markedly affected by blood borne glucose-consuming cells accumulated
in the biofouling layer and in the surrounding bulk. CONCLUSIONS: The physical
barrier to glucose transport presented by protein biofouling does not hinder
glucose movement to the sensor surface, and the consumption of glucose by
inflammatory cells, and not erythrocytes, proximal to the sensor surface has a
substantial effect on sensor response and may be the main culprit for anomalous
sensor behavior immediately following implantation.
PMID- 24351182
TI - Description and preliminary evaluation of a diabetes technology simulation
course.
AB - BACKGROUND: We aim to provide data on a diabetes technology simulation course
(DTSC) that instructs internal medicine residents in the use of continuous
subcutaneous insulin infusion (CSII) and continuous glucose monitoring system
(CGMS) devices. METHODS: The DTSC was implemented during calendar year 2012 and
conducted in the institution's simulation center. It consisted of a set of
prerequisites, a practicum, and completion of a web-based inpatient CSII-ordering
simulation. DTSC participants included only those residents in the outpatient
endocrinology rotation. Questionnaires were used to determine whether course
objectives were met and to assess the satisfaction of residents with the course.
Questionnaires were also administered before and after the endocrine rotation to
gauge improvement in familiarity with CSII and CGMS technologies. RESULTS: During
the first year, 12 of 12 residents in the outpatient endocrinology rotation
completed the DTSC. Residents reported that the course objectives were fully met.
The mean satisfaction score with the course ranged from 4.0 to 4.9 (maximum, 5),
with most variables rated above 4.5. Self-reported familiarity with the operation
of CSII and CGMS devices increased significantly in the postrotation survey
compared with that on the prerotation survey (both p < .01). CONCLUSIONS: In this
pilot program, simulation-based education increased the perceived familiarity of
residents with CSII and CGMS technologies. In light of these preliminary
findings, the course will continue to be offered, with further data accrual.
Future work will involve piloting the DTSC approach among other types of
providers, such as residents in other specialties or inpatient nursing staff.
PMID- 24351183
TI - The evidence base for diabetes technology: appropriate and inappropriate meta
analysis.
AB - When we are interested in making decisions about best use, comparative
therapeutic efficacy, or cost-effectiveness of diabetes technologies such as
insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] or
continuous glucose monitoring, meta-analysis for the purpose of literature
summary is inappropriate and may be misleading. Instead, "decision-making meta
analysis" is more appropriate and should involve either preselection of trials
based on intended use [e.g., elevated baseline hemoglobin A1c or hypoglycemia
rate for trials of multiple daily injections (MDI) versus CSII] or metaregression
of summary effect sizes in different trials against potential effect-modifying
covariates such as baseline risk, or models of the covariates that determine
effect size using individual patient data. Appropriate meta-analysis should also
only include trials that are of sufficient duration to accurately measure
outcomes such as severe hypoglycemia, and they should not use obsolete technology
that is of proven inferiority to current technology. The use of appropriate
decision-making meta-analysis is illustrated by the change in the rate ratio for
severe hypoglycemia in randomized controlled trials of MDI versus CSII in type 1
diabetes from 1.56 (95% confidence interval 0.96-2.55; p = .074) for literature
summary meta-analysis to 2.0 (1.08-3.69; p = .027) for decision-making meta
analysis of all patients and 3.91 (1.35-11.36; p = .01) for trials in children.
PMID- 24351184
TI - Blood glucose pattern management in diabetes: creating order from disorder.
AB - BACKGROUND: Self-monitoring of blood glucose (SMBG) is the most accessible way to
assess glycemic patterns, and interpretation of these patterns can provide
reasons for poor glycemic control and suggest management strategies. Furthermore,
diabetes management based on blood glucose (BG) patterns is associated with
improved patient outcomes. The aim of this review is therefore to evaluate the
impact of pattern management in clinical practice. METHODS: We included a review
of available literature, a discussion of obstacles to implementation of SMBG and
pattern management, and suggestions on how clinicians and patients might work
together to optimize this management feature. RESULTS: The literature review
revealed eight publications specifically describing structured approaches to SMBG
and pattern management. Specific information on how SMBG might be structured to
detect BG patterns, however, remains limited. Barriers to pattern management
include not just practical reasons, but emotional and psychological reasons as
well. CONCLUSIONS: Patterns are not always easy to detect or interpret, but on
meter and web-based tools can support both patients and clinicians. Ultimately,
successful pattern management requires education and mutual commitment from the
clinician and patient--ongoing collaboration is needed to obtain, review, and
interpret SMBG values and to make changes based on the patterns.
PMID- 24351185
TI - Assessing the analytical performance of systems for self-monitoring of blood
glucose: concepts of performance evaluation and definition of metrological key
terms.
AB - Reliability of blood glucose (BG) measurements is a prerequisite for successful
diabetes management. Publications on the evaluation of self-monitored glucose
values, however, are frequently characterized by a confusion in terminology. We
provide an inventory of key terms such as accuracy, trueness, precision,
traceability, calibration, and matrix effect to avoid future misunderstanding.
Definitions are taken from the metrological literature and international norms
and explained in a language intended for nonspecialists in metrology. The terms
are presented in light of the need to apply generally accepted definitions. In
addition, a description of requirements and components for a sound evaluation of
BG measurement systems is presented. These factors will also enable improvement
in future comparisons of study results.
PMID- 24351186
TI - Stability and performance of rapid-acting insulin analogs used for continuous
subcutaneous insulin infusion: a systematic review.
AB - AIM: We review and summarize the literature on the safety and stability of rapid
acting insulin analogs used for continuous subcutaneous insulin infusion (CSII)
in patients with diabetes. METHODS: Two predefined search strategies were
systematically implemented to search Medline and the Cochrane Register of
Clinical Trials for publications between 1996 and 2012. RESULTS: Twenty studies
were included in the review: 13 in vitro studies and 7 clinical studies. In vitro
studies investigated the effects of extreme CSII conditions (high temperature and
mechanical agitation) on the risk of catheter occlusions and insulin stability
factors, such as potency, purity, high molecular weight protein content, pH
stability, and preservative content (m-cresol, phenol). Under these conditions,
the overall stability of rapid-acting insulin analogs was similar for insulin
lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed
greater susceptibility to insulin precipitation and catheter occlusions. A
limited number of clinical trials were identified; this evidence-based
information suggests that the rate of catheter occlusions in patients with type 1
diabetes using CSII treatment may vary depending on the rapid-acting analog used.
CONCLUSIONS: Based on a limited amount of available data, the safety, stability,
and performance of the three available rapid-acting insulin analogs available for
use with CSII were similar. However, there is limited evidence suggesting that
the risk of occlusion may vary with the insulin preparation under certain
circumstances.
PMID- 24351187
TI - The concomitant relationship shared by sleep disturbances and type 2 diabetes:
developing telemedicine as a viable treatment option.
AB - Individually, sleep disturbances and type 2 diabetes pose pervasive challenges to
health. In addition, the negative symptomology associated with each condition is
exacerbated further when presenting concomitantly. This relationship formulates a
destructive loop wherein those with diabetes experience decreased sleep quality,
which, in turn, worsens a wide range of health threats experienced by those with
diabetes, including obesity and glucose intolerance. Because major lifestyle
changes and daily care are needed to effectively manage both diabetes and sleep
disturbances, an efficient and timely modality of treatment is essential.
Advanced technology incorporating telemedicine and telehealth has the potential
to enhance treatment by delivering accepted standard of care, medical monitoring,
and education quickly and seamlessly--even in rural locations. This type of
intervention has the added potential benefit of fostering patient empowerment.
PMID- 24351188
TI - Diabetes professionals must seize the opportunity in mobile health.
AB - The number of diabetes management mobile applications (apps) available on the
market has grown exponentially since 2009; however, most patients lack the skills
necessary for finding relevant health care information. Thus, clinical best
practices emphasize the need for ongoing patient education. Despite the
importance of education in clinical guidelines, very few of these apps include
education in their top functionalities. Most diabetes management mobile apps are
not medical devices by definition, according to the U.S. Food and Drug
Administration, and therefore do not require clearance or approval for market,
and very few have been subject to clinical evaluation. There has been little
research on the use of diabetes management mobile apps, marginalizing the role of
diabetes professionals and educators in a burgeoning market, hungry for
information and an improved quality of life. Still, mobile technology holds great
promise as a platform for self-management. Health care providers must not only
educate patients about these resources, but take steps to ensure that mobile apps
follow accepted best practices and guidelines.
PMID- 24351189
TI - Algorithms for a closed-loop artificial pancreas: the case for proportional
integral-derivative control.
AB - Closed-loop insulin delivery continues to be one of most promising strategies for
achieving near-normal control of blood glucose levels in individuals with
diabetes. Of the many components that need to work well for the artificial
pancreas to be advanced into routine use, the algorithm used to calculate insulin
delivery has received a substantial amount of attention. Most of that attention
has focused on the relative merits of proportional-integral-derivative versus
model-predictive control. A meta-analysis of the clinical data obtained in
studies performed to date with these approaches is conducted here, with the
objective of determining if there is a trend for one approach to be performing
better than the other approach. Challenges associated with implementing each
approach are reviewed with the objective of determining how these approaches
might be improved. Results of the meta-analysis, which focused predominantly on
the breakfast meal response, suggest that to date, the two approaches have
performed similarly. However, uncontrolled variables among the various studies,
and the possibility that future improvements could still be effected in either
approach, limit the validity of this conclusion. It is suggested that a more
detailed examination of the challenges associated with implementing each approach
be conducted.
PMID- 24351190
TI - Algorithms for a closed-loop artificial pancreas: the case for model predictive
control.
AB - The relative merits of model predictive control (MPC) and proportional-integral
derivative (PID) control are discussed, with the end goal of a closed-loop
artificial pancreas (AP). It is stressed that neither MPC nor PID are single
algorithms, but rather are approaches or strategies that may be implemented very
differently by different engineers. The primary advantages to MPC are that (i)
constraints on the insulin delivery rate (and/or insulin on board) can be
explicitly included in the control calculation; (ii) it is a general framework
that makes it relatively easy to include the effect of meals, exercise, and other
events that are a function of the time of day; and (iii) it is flexible enough to
include many different objectives, from set-point tracking (target) to zone
(control to range). In the end, however, it is recognized that the control
algorithm, while important, represents only a portion of the effort required to
develop a closed-loop AP. Thus, any number of algorithms/approaches can be
successful--the engineers involved in the design must have experience with the
particular technique, including the important experience of implementing the
algorithm in human studies and not simply through simulation studies.
PMID- 24351191
TI - Could continuous glucose monitoring facilitate identifying diabetes patients with
a higher risk of hypoglycemia during driving?
PMID- 24351192
TI - Assessment of impaired fasting glucose in obese and overweight insulin-resistant
children by continuous glucose monitoring.
PMID- 24351193
TI - Partial pressure of oxygen in capillary blood samples from the fingertip.
PMID- 24351194
TI - High-priority research needs for insulin delivery and glucose monitoring methods.
PMID- 24351195
TI - Concurrent continuous glucose monitoring in critically ill patients: interim
results and observations.
PMID- 24351196
TI - Inspiratory muscle training reduces sympathetic modulation in elderly patients
with insulin resistance.
PMID- 24351197
TI - Glucometer for kids: what do we need?
PMID- 24351198
TI - In response to Teodorczyk and coauthors: System accuracy of blood glucose
monitoring devices according to the current and proposed ISO 15197 standards.
PMID- 24351199
TI - Decreased von Willebrand factor ristocetin cofactor activity and increased
ADAMTS13 antigen increase postoperative drainage after coronary artery bypass
grafting.
AB - OBJECTIVES: Routine coagulation tests and bleed-scores fail to identify patients
at risk of excessive postoperative drainage following coronary artery bypass
grafting (CABG). We sought to investigate whether lower von Willebrand factor
(VWF) and higher ADAMTS13 (a disintegrin and metalloproteinase with a
thrombospondin type 1 motif, member 13) are associated with a high postoperative
drainage after CABG. METHODS: In the prospective cohort study, VWF antigen
(VWF:Ag), VWF ristocetin cofactor (VWF:RCO), VWF collagen-binding (VWF:CB),
ADAMTS13 antigen (ADAMTS13:Ag) and ADAMTS13 activity were measured on the day of
elective on-pump CABG in 232 consecutive patients without a prior history of
haemorrhagic diathesis, including von Willebrand disease (95% discontinued
aspirin preoperatively). Postoperative drainage and blood product use were
recorded. RESULTS: A comparison of extreme drainage quartiles (n=56) showed that
individuals with the highest drainage volumes have mean VWF:RCO lower by 19%
(P<0.0001), median VWF:Ag lower by 19% (P<0.0001), ADAMTS13:Ag higher by 8%
(P=0.0002), ADAMTS13 activity higher by 9% (P=0.01) and fibrinogen lower by 14%
(P=0.03) than those with the lowest drainage. Linear regression analysis showed
that preoperative VWF:RCO (b=-4.83, P=0.002) and fibrinogen (b=-61.52, P=0.04)
are the only independent predictors of postoperative drainage. Multivariate
logistic regression demonstrated that preoperative VWF:RCO in the lowest quartile
and ADAMTS13:Ag levels in the highest quartile increased the risk of high (>=1000
ml) drainage (odds ratio [95% confidence interval]=4.88 [1.83-13.02], P=0.001 and
3.77 [1.49-9.52], P=0.005; respectively). CONCLUSIONS: Patients undergoing
elective CABG with lower preoperative VWF:RCO are at risk of having larger
postoperative drainage, which suggests a novel contributor to increased
perioperative bleeding in cardiac surgery.
PMID- 24351200
TI - Intestinal failure - its nature, pathophysiology and treatment.
AB - The existence of 'intestinal failure' was proposed. This pathologic condition may
occur in two distinct forms, ie short bowel syndrome marked by a gross reduction
in functioning gut mass and impaired intestinal function (impairment of motility
and extensive parenchymatous disorders). This has been newly recognized as a
complex independent entity on account of an increasing number of patients that
now survive thanks to the recent progress in nutritional management, especially
total parenteral nutrition (TPN). In view of many unresolved clinical questions
regarding long-term TPN and loss of gut mass, it is hoped that future research
efforts will be directed towards settlement of these issues and how to surmount
difficulties in bowel transplantation.
PMID- 24351201
TI - The relationship between high maternal aluminum ingestion and anemia-related
hematologic changes in rats.
AB - Microcytic, hypochromic anemia in dialysis patients has been associated with
aluminum toxicity. Since pregnant women and infants are high-risk groups for iron
deficiency anemia, the purpose of this study was to investigate if high maternal
aluminum intake could cause anemia in dams and pups of rats. Eighteen Sprague
Dawley (SD) female weanling rats were arranged in three groups under randomized
completely block design (RCBD) experiment design. Control, Low-Al and High-Al
groups had 0, 500, 2000 mg Al/kg diet added in the basal diet, respectively,
through growing, pregnancy and lactation. Rats were sacrificed after weanling.
Results indicated that either body weight gain or feed efficiency was the lowest
in High-Al groups dams (P<0.05). The body weights were the same in neonates from
mothers with various aluminum intakes. However, the higher the maternal aluminum
intakes, the lower the average body weight of weanling pups (P<0.05). There was a
positive correlation between Al intake and serum Al concentration, Al intake and
milk Al content of dams (r = 0.93 and r = 0.89, respectively; P<0.05). Average
milk and serum aluminum concentrations of dams with high aluminum intake were
higher than those in the Control and Low-Al groups. Nevertheless, serum aluminum
concentration in pups was not different among the three groups. There was no
difference in hematocrit (Hct), hemoglobin (Hb) mean corpuscular hemoglobin
concentration (MCHC), total iron binding capacity, or transferrin saturation
among dams. On the other hand, the pups in the High-Al group had the highest Hct
and Hb per unit body weight compared with the other groups, probably due to
smaller litter size.
PMID- 24351202
TI - Monthly and seasonal variation in plasma lipids in healthy Australian men: a
longitudinal study in Melbourne.
AB - A prospective study of seasonal variability of lipids in 36 healthy men, aged 40
45 years, over 14 months in Melbourne showed significant monthly and seasonal
variation by paired t-test. Measurement of cholesterol and triglycerides was
carried out by standard, automated enzymic assays calibrated with CDC certified
materials. High Density Lipoprotein Cholesterol (HDLC) was measured after
Polyethylene Glycol 6000 precipitation of Apo B containing lipoproteins. Intra
individual variation ranged wisely; Cholesterol: mean Coefficient of Variation
(CV) 6.9%, range 4.1 to 14.0, HDLC: mean CV 9.1%, range 5.3 to 15.6 Low Density
Lipoprotein Cholesterol (LDLC): mean CV 10.2%, range 5.2 to 18.4. The seasonal
effect showed the most favourable lipid/ lipoprotein profile, ie lowest total and
LDLC, highest HDLC to occur in the antipodean summer (Nov/Dec) and the least
favourable profile in winter (Jul/Aug), with highest (total) Cholesterol and
lowest HDLC. This is best observed as the LDLC/HDLC ratio which peaks in July
(3.6), with the trough in December (2.7). This pattern is consistent with
seasonal effects described previously in the northern hemisphere, except that the
months are reversed. Weight did not alter significantly during the period of the
study. Seasonal and individual variation in lipids and lipoproteins should be
taken into account in the clinical management of lipid disorders.
PMID- 24351203
TI - Development of the Melbourne FFQ: a food frequency questionnaire for use in an
Australian prospective study involving an ethnically diverse cohort.
AB - Objective. To develop an optically scannable food frequency questionnaire (FFQ),
'The Melbourne FFQ', suitable for classifying Australian-, Greek- and Italian
born individuals into quantiles of intake for a range of foods and nutrients. The
FFQ would provide the primary measure of dietary exposure in a prospective cohort
study. Design. The FFQ was modelled on that used for the (US) Nurses' Health
Study. Food items were chosen on the basis of their relative contribution to the
intake of a range of nutrients computed from weighed food records. Setting.
Metropolitan Melbourne, Australia, a city of 3 million people, of whom 75.5% were
born in Australia, 2.7% were born in Italy and 1.7% were born in Greece.
Participants. Weighed Food Survey (1987-1989): A volunteer sample of 810 healthy
middle-aged (40-69 years) men and women of whom 35% were born in Greece, 33% were
born in Italy, and 32% were born in Australia. Melbourne Collaborative Cohort
Study (1990-1993): A volunteer sample of 17 949 healthy men and women aged
between 40 and 69 years of whom 61% were born in Australia, 21% were born in
Italy and 17% were born in Greece. Results. A 121 item FFQ was developed,
together with a customized nutrient database. The optical scanning format was
generally well received with the majority of subjects requiring no assistance.
The FFQ appeared to overestimate the consumption of fruit and vegetables.
Conclusions. The Melbourne FFQ provides a convenient method of measuring habitual
dietary intake in a large population setting. A separate study is required to
assess how well the instrument characterizes diet at the level of the individual.
PMID- 24351204
TI - Body composition in the pathogenesis and management of diabetes: a Malaysian
perspective.
AB - There is an increasing prevalence of diabetes mellitus around the world
associated with rapid sociocultural development and changing lifestyles.
Increased prevalence of obesity, with a higher consumption of animal products and
lower consumption of fruits and vegetables, increases the risk of diabetes
mellitus and other chronic degenerative diseases. Insulin-dependent diabetes
(IDD) is caused by insulin deficiency, whereas the main feature of non-insulin
dependent diabetes (NIDD) which accounts for more than 90% of diabetics, is
hyperinsulinemia and insulin resistance, which may eventually lead to actual
insulin deficiency. Hyperinsulinemia is undesirable because it increases the risk
of developing vascular disease. In Malaysia, the prevalence of NIDD in some
communities now exceeds 5%, and of impaired glucose tolerance 10%. Along with
these increases in prevalence of hyperglycemia are increases in prevalence of
overweight (BMI>25) and almost certainly abdominal fatness. In terms of
management, nutrition is given priority. Insulin and hypoglycemic drugs
(sulphonylureas or biguanides), where required, may adversely affect body
composition if overused. Newer therapeutic strategies require greater attention
to the underlying problem in NIDD of abdominal fatness by attention to the
relevant nutritional factors, physical activity and other lifestyle factors like
cigarette smoking and alcohol. The greater impact of obesity and diabetes on
Malaysian women as opposed to men also needs to be addressed.
PMID- 24351205
TI - Intake and food sources of ascorbic acid in China.
AB - Investigating differences in the intake of nutrients is of potential importance
in characterizing diet-disease relationships and determining the level of intake
necessary for optimal health. The intake and food sources of ascorbic acids were
examined in an ecologic study of 64 rural counties in the People's Republic of
China and compared with data reported for the United States. The mean (+/- SEM)
and median individual intakes of ascorbic acid for all counties combined were 140
(+/- 88) and 128 mg/day, respectively (range 6-429 mg/day). This compares to a
mean intake of 99 mg/day for adult men and 84 mg/day for adult women in the
United States. The foods that contributed the most to ascorbic acid intake were
sweet potatoes (37.2%), cabbages (23.9%), leafy green vegetables (10.6%),
radishes (8.8%), and hot peppers (6.5%). In contrast to the US, where fruits
supply 43% of ascorbic acid to the diet, fruits contributed a relatively small
amount to overall ascorbic acid intake in rural China ( 1%). The wide range of
ascorbic acid intake among counties resulted, in part, from differences in the
availability of fresh produce which is grown and consumed locally. Despite this,
the mean intake was still greater than the US because of the large contribution
of plant products (approximately 90%), especially tubers and other vegetables, to
the diet.
PMID- 24351206
TI - Worker rights and health protection for prostitutes: a comparison of The
Netherlands, Germany, and Nevada.
AB - I analyze prostitution policy changes regarding worker rights and health
protection for legal prostitutes in The Netherlands, Germany, and Nevada to
determine whether the changes benefit the prostitutes. I critically analyze and
compare laws, government policy briefs, advocacy studies, books, articles, and
ethnographic studies. Problems were revealed in recognizing prostitution as
legitimate work and in realization of health protection. Health and safety
concerns exist in The Netherlands and Germany where policy does not mandate
health requirements and condom usage. Nevada law requires safety precautions,
health testing, and condom usage, resulting in no legal prostitutes testing
positive for HIV.
PMID- 24351207
TI - Combining single RNA sensitive probes with subdiffraction-limited and live-cell
imaging enables the characterization of virus dynamics in cells.
AB - The creation of fluorescently labeled viruses is currently limited by the length
of imaging observation time (e.g., labeling an envelope protein) and the rescue
of viral infectivity (e.g., encoding a GFP protein). Using single molecule
sensitive RNA hybridization probes delivered to the cytoplasm of infected cells,
we were able to isolate individual, infectious, fluorescently labeled human
respiratory syncytial virus virions. This was achieved without affecting viral
mRNA expression, viral protein expression, or infectivity. Measurements included
the characterization of viral proteins and genomic RNA in a single virion using
dSTORM, the development of a GFP fusion assay, and the development of a pulse
chase assay for viral RNA production that allowed for the detection of both
initial viral RNA and nascent RNA production at designated times postinfection.
Live-cell measurements included imaging and characterization of filamentous
virion fusion and the quantification of virus replication within the same cell
over an eight-hour period. Using probe-labeled viruses, individual viral
particles can be characterized at subdiffraction-limited resolution, and viral
infections can be quantified in single cells over an entire cycle of replication.
The implication of this development is that MTRIP labeling of viral RNA during
virus assembly has the potential to become a general methodology for the labeling
and study of many important RNA viruses.
PMID- 24351210
TI - Editorial.
PMID- 24351209
TI - Becoming poor and the cutback in the demand for health services in Israel.
AB - BACKGROUND: This paper examines whether individuals facing the threat of poverty
are curtailing their consumption of various goods and services in a given order
and, if among the expenditures that are cut back, there are also health
expenditures. The location of individuals in this order of cutback is then used
to derive the degree of their deprivation and the factors that affect the extent
of this deprivation. METHODS: This order of curtailment of expenditures is
obtained on the basis of an algorithm originally devised to derive the order of
acquisition of durable goods. Having found the order of curtailment of
expenditures on the basis of the 2003 Israel Social Survey, we then estimate an
ordered logit regression whose latent dependent variable is assumed to measure
the individual degree of deprivation. RESULTS: The results of this estimation
show that, other things constant, the individual latent level of deprivation
increases with the size of the household, first increases and then decreases with
the age of the individual, is higher when the individual has children under the
age of five, has a low educational level, a low income, and when he/she is
separated or divorced. Finally, deprivation is found to be lower among
individuals with good health. CONCLUSION: Discovering the order of curtailment of
expenditures, including health expenditures, of individuals facing economic
difficulties and finding the determinants of the extent of such deprivation
should help policy makers focus their attention on the population subgroups that
are most likely to curtail their health expenditures when facing economic
difficulties.
PMID- 24351208
TI - Rivaroxaban attenuates leukocyte adhesion in the microvasculature and thrombus
formation in an experimental mouse model of type 2 diabetes mellitus.
AB - INTRODUCTION: Thrombosis is a major complication in diabetes mellitus. Since
Factor Xa inhibitors are not only inhibit the coagulation system but also
attenuate the leukocyte-endothelial interaction in acute inflammation models, the
purpose of this study is to confirm the similar effects of rivaroxaban in a mouse
model of type 2 diabetes mellitus. MATERIALS AND METHODS: In the treatment
groups, either 5 or 10mg/kg of rivaroxaban dissolved in DMSO was orally given to
KK-A(y) mice for 7 weeks (n=6 in each group). KK-A(y) mice fed by chow containing
DMSO without rivaroxaban for 7 weeks were served for the control group (n=6).
Following clamping of the mesenteric vein for 20 minutes, intravital microscopic
observation of the intestinal microcirculation and the measurement of bleeding
time after the needle puncture were carried-out. In another series, the
calculation for blood cell counts and the measurement of blood fluidity using
micro channel array flow analyzer (MC-FAN) were performed. RESULTS: The initial
event in the microvasculature is the leukocyte adhesion on endothelium. Then, the
leukocytes make clusters and the platelets are involved in. These leukocyte
platelet conjugates aggregate and form thrombus. The leukocyte adherence and the
microthrombus formation was significantly suppressed with the treatment of 10
mg/kg of rivaroxaban compared to the control group (P<0.05). While, the bleeding
time was significantly extended with the treatment with 10mg/kg of rivaroxaban
(P<0.01). The blood fluidity was maintained best with the treatment of 10 mg/kg
rivaroxaban. CONCLUSIONS: Rivaroxaban attenuates the leukocyte-platelet
endothelial interaction, which leads to the attenuation of microthrombus
formation in a mouse model of diabetes mellitus.
PMID- 24351211
TI - Determination of Brain Volumes Using Quantitative MR Imaging in Patients with
Multiple Sclerosis.
AB - The purpose of this study was to determine the amount of atrophy occurring in the
cerebrum of patients with multiple sclerosis compared with controls, and to show
the relationship between clinical status and distribution of atrophy. MR images
were obtained on 12 relapsing-remitting (RR) and 11 secondary progressive (SP)
multiple sclerosis patients and 24 control subjects (all patients and controls
were female). The Cavalieri method by modern design stereology was used to
measure the cerebral volume. It was found that volumes for RR and SP with
multiple sclerosis and control subjects were 757242 mm(3), 716867 mm(3) and
912499 mm(3) respectively. Mean estimates of volume loss in RR and SP were 20.5%
and 27.2% respectively compared to controls for the cerebrum. In addition the
volume difference between RR and SP was 5.6%. There were statistically
significant differences between both RR (P<0.05) and SP (P<0.05) compared with
control subjects but no differences between RR and SP volumes. MRI-estimated
cerebrum volumes may be help to evaluate patients' clinical status and provide a
simple index to assess the efficiency of therapy.
PMID- 24351212
TI - Morphologic and volumetric analysis of amygdala, hippocampus, fornix and
mamillary body with MRI in patients with temporal lobe epilepsy.
AB - Our aim was to demonstrate lateralization morphometrically and volumetrically
measuring the main limbic structures like hippocampus, amygdala, fornix and
mamillary bodies in patients with temporal lobe epilepsy (TLE) and to establish
the contribution of each anatomical structure to lateralizing the pathological
site. Forty-two patients with complex partial seizures originating from the
temporal lobe and 42 control healthy volunteers were included in the study. T2
weighted FSE sequences in axial and oblique coronal planes and T1-weighted SE
sequences in the sagittal plane were used. A high-resolution IR sequence was used
for the volumetric analysis of amygdala and hippocampus and for the measurement
of fornix and mamillary body thickness. Intensity changes and atrophy of limbic
structures were observed qualitatively and measurement of these structures was
performed quantitatively. Student's t test and Mann-Whitney U-test were used for
the statistical analysis. The p values <0.05 was taken as statistically
significant. Ten out of 42 patients had intracranial masses and were excluded
from the study. Qualitative analysis revealed atrophy in 84% and intensity
increase in 60% of cases. Quantitative measurement demonstrated that control
cases had a larger hippocampus than the patients ( p<0.001). There was unilateral
hippocampal volume loss in 88% and bilateral volume loss in 13% of patients.
There was no difference in the volume of amygdala between the groups ( p>0.05).
According to the difference in the volumes of the right and left sides, there was
unilateral atrophy in 34% of patients. Bilateral atrophy was not observed. There
was a significant difference in fornix and mamillary bodies of the patients and
control subjects ( p<0.005). In 62.5% of cases, there were abnormalities in the
fornix with bilateral involvement in 13% of cases. Mamillary bodies were abnormal
in 37% of patients with bilateral involvement in 15%. Lateralization was
accomplished in 65% of the patients according to the percentage difference ratios
of fornix and in 38% of the patients according to the mamillary bodies. It is
important to demonstrate hippocampus atrophy in patients with TLE. In the
decision of lateralization of the epileptic side, evaluation of the fornix could
be a good and practical solution. However, hippocampal volumetry is an
indispensable criterion in demonstrating hippocampal atrophy more accurately.
Atrophy of the amygdala and thickness of mamillary bodies have the least
importance for lateralization.
PMID- 24351213
TI - Creutzfeldt-jakob disease. The value of diffusion-weighted MRI.
AB - Creutzfeldt-Jakob disease (CJD) is a transmissible, progressive, fatal spongiform
encephalopathy. An early and accurate diagnosis is important to prevent disease
transmission, but diagnosis is not easy, especially in the early stage of the
disease. MRI plays an important role in the early diagnosis and differentiating
the entity form other disorders.
PMID- 24351214
TI - Focal Lesion in Splenium of Corpus Callosum on FLAIR MRI: Common Findings in Aged
Patients.
AB - Focal high signal intensity in the splenium of the corpus callosum on fluid
attenuated inversion-recovery (FLAIR) images is generally considered an abnormal
MR finding. The aim of this study was to determine the frequency of this finding
in elderly patients and review the differentiation from other diseases with the
similar findings. FLAIR images of 132 patients with suspect CNS disease were
retrospectively reviewed. The changes in the splenium of corpus callosum, deep
white matter lesions, periventricular matter lesions, infarcts, atrophy and age
were analyzed, as well as history. Among the initial 132 patients, focal high
signal intensity in the splenium was associated with aging, white matter changes,
atrophy, and cognitive disorders. Focal high signal intensity in the splenium of
the corpus callosum on FLAIR image is a common finding in elderly patients,
especially in aged patients with cognitive disorders. The pathologic alterations
were commonly described by the term of "leukoaraiosis". Knowledge of this finding
and differentiation from other lesions focusing on the splenium of corpus
callosum may help avoid unnecessary invasive diagnostic and therapeutic
intervention.
PMID- 24351215
TI - Functional MRI in Patients with Intracranial Lesions near Language Areas.
AB - We aimed to depict Broca's area and Wernicke's area by word generation and
sentence formation paradigms in patients with various intracranial lesions
adjacent to language areas using functional MRI technique and to evaluate the
ability of functional MRI to lateralize the hemispheric dominance for language.
Twenty-three right-handed patients were included in this study. Lesions were
classified as low-grade glioma (n=8), high-grade glioma (n=9), metastasis (n=1),
meningioma (n=1), arteriovenous malformation (n=2) and mesial temporal sclerosis
(n=2). We performed blood-oxygenated-level-dependant functional MRI using a 1.5-T
unit. Word generation and sentence formation tasks were used to activate language
areas. Language areas were defined as Brodmann 44, 45 (Broca's area) and Brodmann
22 area (Wernicke's area). Laterality index was used to show the dominant
hemisphere. Two poorly cooperative patients showed no activation and were
excluded from the study. Broca's area was localized in 21 patients (100 %).
Wernicke's area, on the other hand, could only be localized in eight of the 21
patients (38 %).The left hemisphere was dominant in 86% of patients while
atypical language lateralization (right or bilateral) was demonstrated in 14% of
the patients. Bilateral activation areas were shown in 10% of those patients
while right cerebral hemisphere was dominant in 4% of the patients. Word
generation and sentence formation tasks are especially helpful in localizing
Broca's area. Wernicke's area could also be demonstrated in some of the cases.
Functional MRI can be used as an important and useful means of demonstrating
language areas in patients with lesions adjacent to those areas and depicting the
hemispheric dominance.
PMID- 24351216
TI - Acute Encephalitis of Unknown Etiology: Early Diagnosis and Follow-up of Disease
Evolution. MRI. A Pictorial Essay.
AB - Two women with viral encephalitis of unknown etiology were studied with serial MR
studies at 1.5 Tesla using: Spin-Echo (SE) T1-weighted (T1w) sequences before and
after i.v. administration of paramagnetic contrast agent, with/without
magnetization transfer (MT), Fast SE and Fluid-attenuated Inversion Recovery
(FLAIR) T2-weighted sequences, Echo-Planar Single-Shot sequences for the
assessment of water diffusivity (Diffusion Weighted, DW, and Apparent Diffusion
Coefficient maps, ADC). The DW and T1w sequences with MT after contrast were most
useful to detect the initial pathologic alterations, thereby reinforcing the
clinical diagnostic hypothesis and prompting appropriate drug treatment, even if
the laboratory data were not conclusive for viral etiology. In a later phase,
both cases showed MR evidence of lacunar foci in the grey matter, and cortical
laminar necrosis, probably indicating a concomitant hypoxic/ischemic mechanism.
PMID- 24351217
TI - Is there a role for apparent diffusion coefficients in the differential diagnosis
of brain tumors?
AB - We determined the potential benefits of apparent diffusion coefficient (ADC)
values of enhancing-nonenhancing solid portions, cystic-necrotic areas and
surrounding edema in the differential diagnosis of brain tumors. Eighty-eight
patients with brain tumors: 16 low-grade gliomas, 21 high-grade gliomas, 26
metastases and 25 meningiomas were imaged prospectively in a 1.5 Tesla magnetic
resonance (MR) unit. Routine MR imaging and echo-planar diffusion-weighted
imaging (DWI) with b values of 0 and 1000 mm(2)/s were performed. ADC values were
obtained in different tumor parts and peritumoral edema. The ADCs of contrast
enhancing tumor regions were higher in high-grade gliomas than meningiomas
(p<0.05). No significant differences were found in ADCs of contrast-enhancing
regions comparing other tumor groups (p>=0.05). The ADCs in non-enhancing tumor
regions did not differ between low-grade and high-grade gliomas (p>=0.05). The
ADCs in cystic-necrotic regions of tumors and surrounding edema were not
significantly different comparing all tumor groups (p>=0.05). There were no
significant differences between ADCs of contrast-enhancing and non-enhancing
regions of high-grade and low-grade gliomas (p>=0.05). No significant differences
were found in ADCs of contrast-enhancing and non-enhancing areas of tumors
comparing to surrounding edema (p>=0.05). ADC was not found to be useful in
distinguishing different tumor types and its value in the diagnosis of brain
tumors is limited due to considerable overlaps.
PMID- 24351218
TI - CT and MR Imaging in Choroid Plexus Carcinoma. Report of Two Cases.
AB - This case report describes the CT and MR appearances of choroid plexus carcinomas
in children less than two years of age. MR and CT imaging of this rare tumor
revealed intensely enhancing mass lesions in an intraventricular location, the
atrium of the lateral ventricle being the preferred site in children. The tumors
were associated with hydrocephalus and cerebral parenchymal invasion.
PMID- 24351219
TI - Intracranial Lipoma of the Sylvian Fissure: MR and CT Findings. A Case Report.
AB - We present the CT and MR features of a rare intracranial lipoma located in the
right sylvian fissure in a patient who presented with a five-year history of
headache. The lesion was well demonstrated on Fluid Attenuated Inversion Recovery
(FLAIR), Turbo Spin Echo (TSE), T1 weighted and fat supressed T2 weighted
sequences.
PMID- 24351220
TI - Endovascular Treatment of Intracranial Aneurysms: Long-Term Follow-up.
AB - Endovascular treatment of intracranial aneurysms is increasingly used and has
evolved as an alternative to surgical clipping. However, its long-term efficacy
has yet to be established. This retrospective hospital based (tertiary teaching
hospital) study aimed to identify factors that might be important in predicting
initial efficacy of this treatment and a long-term follow-up to study the
clinical and angiographic results of treated aneurysms. A total of 80 aneurysms
in 78 patients were treated and analyzed, and the percentage of occlusion
calculated. Overall, 51/80 (64 %) cases were treated with selective endovascular
coil occlusion and 29/80 (36 %) by parent artery occlusion. The shape of the
aneurysm rest was noted on the immediate post treatment and follow-up angiograms.
Immediate and follow-up clinical status was also noted using the Glasgow outcome
scale. The clinical and radiological changes on follow-up were assessed and
possible factors involved were analyzed. Of the 50 patients of intracranial
aneurysms that underwent selective aneurysm coiling, good immediate outcome
(Glasgow outcome scale 1 and 2) was seen in 36/50 (72 %) cases. Narrow necked
aneurysms showed a good immediate result (90-100 % packing) in all cases 28/28
(100 %). Amongst the wide necked aneurysms, good packing (90-100 %) was achieved
in 17/23 (73 %) cases. Amongst the cases treated with parent artery occlusion,
complete occlusion was noted in 20/29 (69 %) cases. No subarachnoid hemorrhage
was seen in any of the followed up cases of coiled aneurysms. A statistically
significant relationship was noted between aneurysm neck size and immediate
angiographic outcome. Long-term angiographic recurrences were found more often in
large aneurysms. Endovascular treatment of intracranial aneurysms is a safe and
effective treatment modality that offers protection from recurrent subarachnoid
hemorrhage.
PMID- 24351221
TI - Endovascular angioplasty-stenting as a definitive treatment for isolated
spontaneous common carotid artery dissection. A case report.
AB - Isolated spontaneous common carotid artery (CCA) dissection is rare. So far,
surgical or medical treatment have only been reported in a few cases in the
literature. We report a 39-year-old man, diagnosed as isolated spontaneous CCA
dissection one year ago, who experienced a new minor stroke despite medical
treatment. Because of the presence of new ischemic lesions on new magnetic
resonance imaging despite medical treatment, and critical narrowing of internal
carotid artery (ICA) orifice with jet and turbulence flow pattern at the bulbar
portion of the ICA, endovascular management was performed with carotid stent
deployment. To the best of our knowledge, this is the first case of spontaneous
isolated CCA dissection treated with stenting of the carotid artery reported in
literature. - OZET - Izole spontan common carotid arter (CCA) diseksiyonu
nadirdir. Literaturde sadece birkac adet, medikal veya cerrahi tedavi uygulanan,
CCA diseksiyonu olgusu bildirilmistir. Bildirimizde, bir yil once izole spontan
CCA diseksiyonu tanisi almis ve medikal tedavi altinda iken yeni minor strok
geciren 39 yasinda erkek olguyu sunuyoruz. Olgunun yeni magnetik rezonans
goruntulemesinde (MRG), sol posterior frontal ve pariyetal loblarda yeni iskemik
lezyonlarin ortaya ciktigi goruldu. Renkli Doppler ultrasonografi (RDUS)
incelemesinde eski incelemesine gore darligin arttigi izlendi. Karotis
anjiografide de internal karotis arter baslangicinda jet ve turbulans akima neden
olan kritik darlik saptanmasi uzerine endovaskuler tedavi planlandi. Femoral
girisimle koruyucu filtre kullanilarak self ekspandibl stent yerlestirildi ve
postdilatasyon balon uygulandi. Islemden 24 saat sonra alinan difuzyon MRG
incelemesinde yeni iskemik alan gorulmedi. Birinci ve 3. ay kontrollerinde,
norolojik muayenesinde yeni bulgu saptanmadi. RDUS incelemelerinde stentin acik
oldugu goruldu. Karotis artere stent yerlestirimesi cerrahiye alternatif bir
tedavi olup daha az invazivdir. Stent uygulamasi, spontan ve travmatik internal
karotis arter darliklarinda kullanilmis, ancak izole spontan CCA diseksiyonunda
kullanilmamistir. Olgumuz nadir gorulen izole spontan CCA diseksiyonu
olgularindan biri olup stent yerlestirilerek tedavi edilmistir. Sonuc olarak,
medikal tedaviye ragmen tekrarlayan semptomlari olan izole spontan CCA
diseksiyonu olgularda tromboemboli kaynaginin kontrol altina alinmasi ve yeterli
karotis akiminin saglanmasi icin stent yerlestirilmesi gerekebilir.
PMID- 24351222
TI - Fusiform basilar artery aneurysm rapid death with occlusion and subdural
subarachnoid hemorrhage.
AB - Fusiform aneurysms of the posterior circulation constitute a relatively uncommon
subgroup of aneurysms. We present a patient with fusiform basilar artery aneurysm
accompanied by ectasia and elongation of both supraclinoid parts of the internal
carotid arteries, middle cerebral arteries and vertebral arteries. The aneurysm
had thrombus formation along its length which progressed to occlude the lumen the
day after the patient's admission. Mass effect, progressive infarcts at the
territories of posterior inferior cerebellar (PICA) and superior cerebellar (SCA)
arteries and brainstem perforators along with subarachnoid and subdural
hemorrhage were present.
PMID- 24351223
TI - Short, medium and long term efficacy of epidurally injected anaesthetic
corticosteroid mixture in lumbocruralgia and lumbosciatalgia.
AB - We assessed the efficacy of an epidural sited anaesthetic-corticosteroid mixture
with transforaminal or interlaminar/interspinous access, in subjects with chronic
lumbocruralgia or lumbosciatalgia caused by discal pathology or degenerative
foraminal stenosis. From September 2003 to June 2005, 84 patients were treated in
the transforaminal region and 32 in epidural space through back access
(interlaminar or interspinous) with 2 ml cortisone (megacort) and 2ml anaesthetic
(naropine 7.5mg/ml). All 116 patients underwent a minimum of two and a maximum of
three treatment sessions. The results were evaluated for a follow-up period of
ten months by comparing the answers given by the patients with the Visual
Analogic Score. This was done prior to and after every single injection and
during the follow-up period. Out of 142 spaces treated, improvement of symptoms
for a period varying from one to three months was recorded in 74 cases (52%), for
a period of more than three months in 53 (37%) cases, while in the remaining 15
(11%) cases no sufficient regression of pain was reported. In many cases of
chronic lumbago/lumbosciatalgia, the percutaneous injection of an anaesthetic
cortisone mixture can be useful in relieving or even killing pain for a period of
more than three months. No major complication was reported.
PMID- 24351224
TI - MRI evaluation of diastematomyelia and associated abnormalities.
AB - Fourteen children were studied with a 1Tesla scanner to assess the role of
magnetic resonance (MR) imaging in the recognition and evaluation of
diastematomyelia and associated abnormalities. With MRI divided spinal cord was
well imaged in its entire craniocaudal extent. Fibrous bands or bony septum when
it contained a marrow cavity, were also well depicted. Direct visualization of
the spinal cord itself is probably the most rewarding feature of MR imaging
compared with other more conventional techniques. MR imaging demonstrated
associated syringohydromyelia, segmentation anomalies, scoliosis, low position of
the conus medularis and intradural lipoma that they were not detected with other
radiologic studies.
PMID- 24351225
TI - MRI determination of conus medullaris level in an adult population in Turkey.
AB - The level of the conus medullaris (CM) in adults has been described in many
studies with cadavers and living people. T1-weighted sagittal spin-echo MR images
of the lumbar spine were reviewed in 364 consecutive patients (207 women, 157
men) with a mean age of 45 years (range 18-80). The most common level of CM was
the L1-L2 intervertebral disc level in females and the T12-L1 intervertebral disc
level in males. The distribution of CM location in a large adult population was
shown to range from the T11-T12 intervertebral disc level to L2-L3 intervertebral
disc level.
PMID- 24351226
TI - Synovial cyst of dens axis. A case report.
AB - Synovial cyst of dens axis is a rare pathology accounting for 0.5%-1% of all
cases of spinal synovial cysts. The lesion is normally found in the final part of
the lumbar tract. The etiopathogenesis is uncertain and many theories abound
Clinical inspection is important and the symptoms are caused by compression of
posterior roots of spinal nerves and by spinal canal stenosis. Differential
diagnosis is with disc herniation or tumours, but the diagnosis can only be
established after CT and MRI examination. We describe the case of an 83-year-old
man who underwent radiological exmaination after ten years of symptoms. The
pathology was diagnosed only after the CT and MRI investigation.
PMID- 24351227
TI - An unmasked neurological pathology (schwannoma) following spinal anesthesia.
AB - A neurological deficit occurred following spinal anaesthesia that unmasked a
relatively important neurological pathology. Spinal anesthesia was performed
between L3 and L4 by midline approach at the first attempt. Postoperative
clinical examination of the patient showed sensory loss below the T5 segment.
Whenever new neurological signs are seen after regional anesthesia, further
investigations should be done immediately for differential diagnosis. - OZET -
Spinal anestezi sonrasi gelisen oldukca onemli bir norolojik patolojiyi kapsayan
olgu sunuldu. Spinal anestezi ilk girisimde L3-4 arasindan orta hattan
gerceklestirildi. Postoperatif klinik muayenesinde T5 segmentinin altinda duyusal
kayip tespit edildi. Rejyonel anestezi sonrasi ne zaman yeni norolojik bulgular
gozlenirse ayirici tani icin hemen ileri tetkikler yapilmalidir.
PMID- 24351228
TI - Percutaneous sclerotherapy for lymphangioma and soft-tissue venous malformation
located in the maxillofacial region in children and young adults.
AB - To demonstrate that percutaneous sclerotherapy for lymphangioma using a new
fibrosing agent (OK-432) and for soft-tissue venous malformation with
alcoholization can improve management of these congenital vascular abnormalities.
Between February 2003 and November 2005 five patients with lymphangioma, ranging
in age from 23 months to 18 years (mean age = 9 years) and four patients with
soft-tissue venous malformation, raging in age from 25 months to 18 years (mean
age = 11 years) underwent percutaneous sclerotherapy. Ultrasound Computed
tomography and/or Magnetic Resonance imaging were performed beforehand to
evaluate the anatomic boundaries of the malformation. General anesthesia is
mandatory for children under three years. Direct puncture of the mass with a 23
gauge venous infusion set (butterfly) was performed by means of palpation alone
or with ultrasonographic guidance using OK-432 PICIBANIL (0.1-0.2 mg dilute in 10
ml normal saline) for lymphangioma and alcohol in venous malformation. The volume
of sclerosing solution varied from 0.2 to 15 ml per injection course. Processing
time was less than 20 minutes. Swelling of lesion, pain, local inflammatory
reactions and mild fever (37.5 degrees -39 degrees ) in lymphangioma, were
constant findings after sclerotherapy. Satisfactory results (when the regression
was estimated to be more than 50% of the initial volume; negative in inspection,
but positive in palpation and imaging study) were obtained in four patients with
head and neck lymphangioma. One patient was completely cured with an excellent
(when there was a complete regression of malformations; negative in inspection,
palpation and imaging study) result. All patients with soft-tissue venous
malformation were satisfied with the results. In conclusion, in consideration of
its low cost, rare complications and good results, we strongly recommend
percutaneous sclerotherapy in the treatment of head and neck lymphangioma and
soft-tissue venous malformation in children.
PMID- 24351229
TI - Transoesophageal echocardiography in patients with stroke and low risk of embolic
etiology.
AB - Transoesophageal echocardiography (TEE) is currently the gold standard in the
diagnosis of cardiac sources of embolization and the frequently discussed
question is whether all patients with suspected embolic stroke should be screened
by TEE. Based on the results of transthoracic echocardiography (TTE), we
determined the significance of TEE in patients with ischemic stroke with low risk
of embolic etiology. We made a retrospective evaluation of TEE examination in the
period from 1(st) January 2000 to 31(st) December 2003 in patients with ischemic
stroke and sinus rhythm and normal left ventricular function. TEE examination was
done in 159 patients. A quarter of the patients had pathological findings in the
heart: left atrial thrombus in nine (5.7%), spontaneous echocontrast in left
atrium in 14 (8.8%), patent foramen ovale in 16 (10%) and other findings in seven
(4.4%) patients. The finding of the thrombus or echocontrast in the left atrium
correlated with the size of the left atrium and it was proved in the patients
with left atrium of size above 39 mm. On the contrary, patent foramen ovale was
found in younger patients (70 vs. 59 years). Our results have shown that TEE is
of low relevance to patients with a normal transthoracic echocardiogram.
PMID- 24351230
TI - Temporal trends of PCDD/Fs in Baltic Sea sediment cores covering the 20th
century.
AB - The pollution trend of polychlorinated dibenzo-p-dioxins and dibenzofurans
(PCDD/Fs) in the Baltic Sea region was studied based on depth profiles of PCDD/Fs
in sediment cores collected from six offshore areas, eight coastal sites impacted
by industrial/urban emissions, and one coastal reference site. A general trend
was observed for the offshore and coastal reference sites with substantial
increase in PCDD/F concentrations in the mid-late 1970s and peak levels during
1985-2002. The overall peak year for PCDD/Fs in Baltic Sea offshore areas was
estimated (using spline-fit modeling) to 1994 +/- 5 years, and a half-life in
sediments was estimated at 29 +/- 11 years. For the industrial/urban impacted
coastal sites, the temporal trend was more variable with peak years occurring 1-2
decades earlier compared to offshore areas. The substantial reductions from peak
levels (38 +/- 11% and 81 +/- 12% in offshore and coastal areas, respectively)
reflect domestic and international actions taken for reduction of the release of
PCDD/Fs to the environment. The modeled overall half-life and reductions of
PCDD/Fs in offshore Baltic Sea sediment correspond well to both PCDD/F trends in
European lakes without any known direct PCDD/F sources (half-lives 30 and 32
years), and previously modeled reduction in atmospheric deposition of PCDD/Fs to
the Baltic Sea since 1990. These observations support previous findings of a
common diffuse source, such as long-range air transport of atmospheric emissions,
as the prime source of PCDD/Fs to the Baltic Sea region. The half-life of PCDD/Fs
in Baltic Sea offshore sediments was estimated to be approximately 2 and 4-6
times longer than in semirural and urban European air, respectively. This study
highlights the need for further international actions to reduce the levels of
PCDD/Fs in Baltic Sea air specifically and in European air in general.
PMID- 24351231
TI - Hydrogen evolution from neutral water under aerobic conditions catalyzed by
cobalt microperoxidase-11.
AB - A molecular electrocatalyst is reported that reduces protons to hydrogen (H2) in
neutral water under aerobic conditions. The biomolecular catalyst is made from
cobalt substitution of microperoxidase-11, a water-soluble heme-undecapeptide
derived from the protein horse cytochrome c. In aqueous solution at pH 7.0, the
catalyst operates with near quantitative Faradaic efficiency, a turnover
frequency ~6.7 s(-1) measured over 10 min at an overpotential of 852 mV, and a
turnover number of 2.5 * 10(4). Catalyst activity has low sensitivity to oxygen.
The results show promise as a hydrogenase functional mimic derived from a
biomolecule.
PMID- 24351232
TI - Serum levels of brain-derived neurotrophic factor (BNDF) in multiple sclerosis
patients with Trichuris suis ova therapy.
AB - We previously analysed clinical and immunological parameters under Trichuris suis
ova (TSO) therapy in four patients with secondary progressive multiple sclerosis.
The serum Brain-derived neurotrophic factor (BDNF) levels of these four patients
were assessed before, during and after therapy with TSO and showed significant
decrease of BDNF during TSO therapy (p < 0.05).
PMID- 24351233
TI - Pregabalin long-term treatment and assessment of discontinuation in patients with
generalized anxiety disorder.
AB - Discontinuation effects following cessation of 12 and 24 wk of pregabalin
treatment for generalized anxiety disorder (GAD) were evaluated in a placebo- and
lorazepam-controlled, randomized, double-blind, multicentre trial conducted in 16
countries. The study design consisted of two 12-wk treatment periods (periods 1
and 2), each followed by a 1-wk taper and two post-discontinuation assessments,
one immediately following the taper and one 1-wk post-taper. Patients were
assigned to receive an initially flexible dose of pregabalin 450-600 mg/d,
pregabalin 150-300 mg/d, or lorazepam 3-4 mg/d for 6 wk; responders continued
fixed-dose therapy for 6 additional weeks. Patients entering period 2 continued
on the same fixed dose or switched to placebo. Discontinuation effects were
evaluated with the Physician Withdrawal Checklist (PWC) and reported
discontinuation-emergent signs and symptoms. Rebound anxiety was measured with
the Hamilton Anxiety Rating Scale. GAD symptoms improved with all treatments and
improvements were maintained over 12 and 24 wk. Low levels of discontinuation
symptoms were evident in all treatment groups. For patients who received active
treatment during both periods, mean (95% confidence interval) increases on the
PWC from last visit on active treatment to the second post-discontinuation
assessment were: pregabalin 450-600 mg/d: 2.8 (1.6-3.9), pregabalin 150-300 mg/d:
1.7 (0.7-2.8), lorazepam 3-4 mg/d: 2.2 (1.0-3.5). Rates of rebound anxiety were
also low at both 12 and 24 wk (0-6%). This suggests that risk of discontinuation
symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of
treatment.
PMID- 24351235
TI - The nutritional status of pre-school children in poor rural areas of China.
AB - Described are the main findings of the first large-scale nutrition monitoring
project carried out over a 4-year period in China. The nutritional status of
nearly 10 000 preschool children in 18 comparatively poor rural areas in seven
provinces was followed each year over the period 198S89 in order to identify
their major nutritional problems and improve their growth and development.
Physical measurements were made and dietary surveys and biochemical tests were
performed on a subsample of the children. The proportion of stunted and
underweight children was far higher than the national average. Based on the
possibilities offered by local circumstances, the prevalences of stunting and
underweight were lowered and anemia greatly reduced. Along with the progress in
nutrition monitoring, major efforts were made to train health workers, as well as
to encourage increased production of green vegetables, poultry, and small
livestock. The wealth of information collected and the experience gained may
serve as a baseline record, the project currently being expanded to cover 100
counties throughout China.
PMID- 24351236
TI - Secular trend of growth in pre-school children in Singapore.
AB - An anthropometric study was conducted on more than 13 500 children aged 04 years
in 1988. Percentile charts were plotted for height for age, weight for age,
weight for height and head circumference for age. When compared to an earlier
study done in 1972, it was found that Singapore pre-school children had increased
in height by 4.4 %; weight by 10.9 %; and head circumference by 4.1 %. When the
median height for age, weight for age and head circumference for age were plotted
against those of the NCHS charts (1978), Singapore's pre-school children were
generally shorter, lighter and had smaller head circumferences than their
American counterparts of the same age. But, the median weight-for-height for each
age group was comparable to the Americans. The results indicate the secular trend
of growth in Singapore children and a trend towards reaching their full genetic
potential for growth.
PMID- 24351234
TI - Fingerprint changes in CSF composition associated with different aetiologies in
human neonatal hydrocephalus: glial proteins associated with cell damage and
loss.
AB - BACKGROUND: In hydrocephalus an imbalance between production and absorption of
cerebrospinal fluid (CSF) results in fluid accumulation, compression and
stretching of the brain parenchyma. In addition, changes in CSF composition have
a profound influence on the development and function of the brain and together,
these can result in severe life-long neurological deficits. Brain damage or
degenerative conditions can result in release of proteins expressed predominantly
in neurons, astroglia, or oligodendroglia into the brain interstitial fluid, CSF
and blood. Determination of such products in the CSF might be of value in
diagnosing cause, aetiology and/or assessing the severity of the neurological
damage in patients with hydrocephalus. We therefore analysed CSF from human
neonates with hydrocephalus for these proteins to provide an insight into the
pathophysiology associated with different aetiologies. METHODS: CSF was collected
during routine lumbar puncture or ventricular tap. Samples were categorized
according to age of onset of hydrocephalus and presumed cause (fetal-onset, late
onset, post-haemorrhagic or spina bifida with hydrocephalus). Glial fibrillary
acidic protein (GFAP), myelin basic protein (MBP), vimentin and 2' , 3'-cyclic
nucleotide 3'-phosphodiesterase (CNPase) were analysed through Western blotting
of hydrocephalic CSF samples (n = 17) and compared with data from CSF of normal
infants without neurological deficits (n = 8). RESULTS: GFAP was significantly
raised only in CSF from post-haemorrhagic hydrocephalus while MBP was
significantly raised in post-haemorrhagic and in spina bifida with hydrocephalus
infants. Vimentin protein was only detected in some CSF samples from infants with
late-onset hydrocephalus but not from other conditions. Surprisingly, CNPase was
found in all neonatal CSF samples, including normal and hydrocephalic groups,
although it was reduced in infants with late onset hydrocephalus compared with
normal and other hydrocephalic groups. CONCLUSIONS: Apart from CNPase, which is
an enzyme, the markers investigated are intracellular intermediate filaments and
would be present in CSF only if the cells are compromised and the proteins
released. Raised GFAP observed in post-haemorrhagic hydrocephalus must reflect
damage to astrocytes and ependyma. Raised MBP in post-haemorrhagic and spina
bifida with hydrocephalus indicates damage to oligodendrocytes and myelin.
Vimentin protein detected in some of the late-onset hydrocephalic samples
indicates damage to glial and other progenitors and suggests this condition
affects periventricular regions. The presence of CNPase in all CSF samples was
unexpected and indicates a possible novel role for this enzyme in brain
development/myelination. Less CNPase in some cases of late-onset hydrocephalus
could therefore indicate changes in myelination in these infants. This study
demonstrates differential glial damage and loss in the developing human neonatal
hydrocephalic brain associated with different aetiologies.
PMID- 24351237
TI - Factors associated with obesity in primary-school children in Singapore.
AB - An upward trend in obesity has been observed in Singapore school children over
the 15 years prior to the study. A case-control study of 400 children (mean age
10 years) and their parents was conducted to determine some of the factors likely
to be associated with obesity in primary-school children. It included dietary
practices and intake, activity patterns, family history and social factors. It
was found that obese children were more likely to consume foods that were deep
fried or sweet and were more likely to have at least one obese parent and
sibling. A variety of intervention measures were taken to reduce the prevalence
and severity of obesity in school children following the study.
PMID- 24351238
TI - Adiposity, dietary and physical activity patterns in ethnic Chinese youths: a
cross-country comparison of Singaporean Chinese and Chinese Americans.
AB - During the last decade, childhood obesity has been on the increase in Singapore
and many newly industrialized Asian countries. We compared the mean body mass
index (BMI) and triceps skinfold (TSF) values, as well as the dietary and
physical activity patterns of Singaporean Chinese and Chinese American youths.
Chinese Americans had a higher mean BMI but a lower mean TSF than Singaporean
Chinese. Dietary comparisons suggest that Singaporean Chinese ate fish and grain
products more often than Chinese American youths, while Chinese American youths
consumed processed meats, dairy products and snack foods more frequently. Mean
frequency of consumption of low fat, traditional Chinese foods such as rich
porridge was higher among the Singaporean Chinese, while typical 'American' foods
including cheese were consumed more often among the Chinese Americans. Certain
food items that were more 'neutral' in terms of their cultural identity, such as
carbonated drinks, cookies and bread were consumed with the same mean frequencies
in both cohorts. In terms of physical activity, Singaporean Chinese youths, on
average, spent more time in sedentary activities, less time sitting, and more
time in light or moderate activities. The mean time spent on vigorous activities
per day was only one hour in both cohorts. Our study suggests differences in body
fat distribution and composition, as well as in dietary and activity patterns,
between Chinese American and Singaporean Chinese youths. There is a need to
develop obesity indicators that are appropriate for the specific populations
involved, and to carefully investigate environmental influences on childhood
obesity.
PMID- 24351239
TI - The current dietary practice of Hong Kong adolescents.
AB - In Hong Kong, blood lipid profiles of adults and children are comparable to the
western industrialized nations. The age on-set of ischemic heart disease in Hong
Kong is gradually declining to occur in younger adults. Dietary practices of
adolescents influence food habits later in life. However, published data on
current dietary intakes of Hong Kong adolescents are scanty. This paper reports a
dietary survey of current food habits in 179 12-year-old adolescents using a food
frequency questionnaire. The mean +/- SD intake of energy, protein, fat,
carbohydrate, cholesterol, calcium, iron, vitamin C and fibre were 2164+/- 766
kcal,107 +/- 44g,71+/-33 g,274+/- 91g, 481+/- 246 mg, 643+/- 252 mg, 16+/- 6mg,
78+/- 41 mg and 3.5+/- 2g, respectively. The percentages of energy derived from
protein, fat, carbohydrate, polyunsaturated fats, monounsaturated fats and
saturated fats were 19.7%, 28.8%, 51.5%, 4.4%, 11.5% and 10.4%, respectively,
whereas the P/S ratio was 0.43. Protein intake was 2.5 times higher than the
FAO/WHO/UNU RDAs, animal protein was the predominant source of protein; meat was
the principal source of fat intake (45%), over 61 % of the individuals had
saturated fat intake greater than 10% (% energy); mean cholesterol intake was 481
mg/d and 79% of the individuals had cholesterol intake above 300 mg/d. Low fibre
intake was related to low intake of unrefined grains, vegetables and fruits. A
high intake of animal products, cholesterol, a low P/S ratio and low consumption
of unrefined grains, vegetables and fruits might be detrimental to a healthy
heart. The increasing frequency of eating out at restaurants and fast-food
outlets and relatively fewer meals being prepared and eaten at home is a growing
concern for maintaining a healthy diet. Immediate action has to be taken to
evaluate the current dietary practices of the population to establish appropriate
healthy eating policy and guidelines in order to prevent the future risks of
developing diet-related chronic diseases.
PMID- 24351240
TI - The difference in food and nutrient intake between smokers and non-smokers in an
elderly Chinese population in Beijing, China.
AB - This study examined variations in dietary intake, which were associated with
differences in education, lifestyle and health behaviours of elderly men and
women (n=305) in Beijing Twenty-four-hour dietary recalls were obtained through
in-home interview. Nutrient analyses of the reported diets were carried out using
the Chinese nutrient database. It was found that more men than women smoked and
that alcohol consumption was associated with smoking. Smokers had a lower intake
of vitamin C (P<0.01), carotenoids (P<0.05) and calcium (P<0.05) than non-smokers
in both genders. Female smokers also showed a lower intake of fruits, vegetables
and milk compared with female non-smokers.
PMID- 24351241
TI - Ethnic characteristics of coronary heart disease risk factors and mortality in
peninsular Malaysia.
AB - The types and prevalence of coronary heart disease (CHD) risk factors vary
somewhat among the three main ethnic groups in peninsular Malaysia. Indians
consistently show the highest prevalence for hypercholesterolemia and diabetes
mellitus. Among the Malays, a relatively high prevalence of hypertension and
hypertriglyceridemia have been reported. Overweight is also a risk factor among
the Indians and Malays. In general, Chinese tend to have a lower prevalence for
these CHD risk factors than the Indians and Malays. Parallel to the rapid socio
economic development and urbanization in recent decades is a rise in the
percentage of deaths due to cardiovascular disease in peninsular Malaysia, that
is from 1.8% of total deaths from all causes in 1950 to about 30% in 1991.
Coronary heart disease accounts for 40% of all cardiovascular diseases. The
mortality rate for CHD has more than doubled between 1965 and 1991, from 24.6 per
100 000 to 57.2. While Indians have been showing the highest CHD mortality rate
so far, that of the Malays has been increasing most rapidly since 1970,
concomitant with the latter's increase in their proportion of the urban
population in peninsular Malaysia.
PMID- 24351243
TI - Foreword.
PMID- 24351244
TI - Imaging of craniofacial and sinonasal anomalies.
AB - Whereas CT imaging techniques such as multiple detector spiral imaging with multi
planar reconstructions are desirable in the evaluation of congenital and
developmental anomalies of the midface and skull base, there is an essential role
for MRI whenever there are related intracranial anomalies. This presentation will
focus on describing and classifying the known craniofacial anomalies that have
common manifestations in the sinonasal regions, the orbits, and the skull base.
Diagrams and clinical cases are utilized to demonstrate the key embryological
events leading to the common dysplasias of the craniofacial and sinonasal
regions.
PMID- 24351242
TI - Bucephalidae (Digenea) from epinephelines (Serranidae: Perciformes) from the
waters off New Caledonia, including Neidhartia lochepintade n. sp.
AB - Many bucephalid species, mainly of the subfamily Prosorhynchinae, have been
described from epinepheline serranids (groupers) throughout the World's Oceans.
In this paper eight named prosorhynchine species are described and/or illustrated
from epinepheline fishes from New Caledonia. Neidhartia lochepintade n. sp. in
Epinephelus chlorostigma differs from other Neidhartia spp. in various
combinations of distinct body-size, rhynchus size, previtelline and pre-mouth
distance, post-testicular distance, cirrus-sac reach and egg-size. Other species
are: Neidhartia haywardi Bott, Miller & Cribb, 2013 in Plectropomus leopardus;
Neidhartia tyleri Bott, Miller & Cribb, 2013 in Plectropomus leopardus and
Plectropomus laevis; Prosorhynchus freitasi Nagaty, 1937 in Plectropomus
leopardus and Plectropomus laevis; Prosorhynchus robertsthomsoni Bott & Cribb,
2009 in Cephalopholis argus; Prosorhynchus longisaccatus Durio & Manter, 1968 in
Cephalopholis urodeta, Epinephelus areolatus, Epinephelus cyanopodus and
Epinephelus maculatus. Prosorhynchus luzonicus Velasquez, 1959 and Prosorhynchus
sp. B. in Epinephelus coioides; Prosorhynchus serrani Durio & Manter, 1968 in
Variola albimarginata and Variola louti; Prosorhynchus sp. A in Epinephelus
morrhua; Prosorhynchus sp. immature in Epinephelus coeruleopunctatus. The new
combination Neidhartia longivesicula (Bilqees, Khalil, Khan, Perveen & Muti-ur
Rehman, 2009) (Syn. Prosorhynchus longivesicula) is formed. Evidence from this
paper and earlier molecular studies indicates that there are numerous
morphologically similar prosorhynchine species in serranids, most of which show a
high degree of host-specificity.
PMID- 24351245
TI - Measuring CSF Flow in Chiari I Malformations.
AB - Cardiac-gated Phase Contrast MR (PC MR) is used in the evaluation of the Chiari I
malformation to assess the CSF flow though the foramen magnum. Images may show
reduced CSF flow posterior to the spinal cord in patients with a Chiari I
malformation. MR images however do not differentiate with sufficient accuracy
between symptomatic and asymptomatic Chiari I malformations. In the presence of
the Chiari I malformation, CSF velocities are elevated. Measuring the velocity of
flow and determining the degree of inhomogeneity in CSF flow aid in the detection
of clinically significant flow abnormalities.
PMID- 24351246
TI - Dementia: What is it All About?
AB - Dementia is an increasingly frequent clinical syndrome that is characterised by
deficits in multiple cognitive domains, changes in behaviour and functional
deterioration. Alzheimer's disease, together with vascular dementia, account for
2/3 of all cases of dementia. Other less frequent causes of dementia include
dementia with Lewy bodies and frontotemporal dementia. This paper reviews the
clinical, pathophysiological and neuroimaging aspects of these four prevalent
causes of dementia.
PMID- 24351247
TI - Imaging dementing illnesses.
AB - Dementia is an impairment of mental ability representing a decline from that
level previously reached by the individual. It is usually of insidious onset,
associated with neurologic changes, and results in the inability to appropriately
interact with one's environment. Dementias may be static, progressive, or
reversible, and have many etiologies. One percent of the population above age 40
suffers from dementia and this figure rises to 7% above age 80 and 50% above age
90. Forty-five percent of dementias are due to Alzheimer disease (AD) followed
closely by vascular dementia. A stage along the way to dementia is mild cognitive
impairment (MCI). There are various definitions but the simplest ones refer to a
person who has some memory problems but can continue to live independently. A
more specific description refers to deficits in two or more areas of cognition
>1.5 SD below mean for the individuals age and education. Although previously
considered a part of normal aging, a recent study has shown MCI to be a precursor
of Alzheimer disease (1). In a cohort of nuns and priests studied annually until
they developed MCI or dementia and died. 180 brains in this study have already
been autopsied (37 MCI, 60 with no impairment, 53 with dementia). Pathologists
measured theamount of AD pathology and cerebral infarcts. Of 37 with MCI, more
than half had AD by pathology, 1/3 had infarcts (5 with both) and 14 did not have
either pathology. One third of the 180 with average age of 85 had no cognitive
decline! Since this study showed MCI patients to have Alzheimer disease pathology
in their brains, recognition of MCI clinically is important for institution of
therapy, although there has not yet been an effective therapy developed.
PMID- 24351249
TI - Reprint of: Radiological assessment of hydrocephalus: new theories and
implications for therapy.
AB - It is almost a century since Dandy made the first experimental studies on
hydrocephalus, but its underlying mechanism has been unknown up to now. The
conventional view is that cerebrospinal fluid (CSF) malabsorption due to
hindrance of the CSF circulation causes either obstructive or communicating
hydrocephalus. Analyses of the intracranial hydrodynamics related to the pulse
pressure show that this is an over-simplification. The new hydrodynamic concept
presented here divides hydrocephalus into two main groups, acute hydrocephalus
and chronic hydrocephalus. It is still accepted that acute hydrocephalus is
caused by an intraventricular CSF obstruction, in accordance with the
conventional view. Chronic hydrocephalus consists of two subtypes, communicating
hydrocephalus and chronic obstructive hydrocephalus. The associated malabsorption
of CSF is not involved as a causative factor in chronic hydrocephalus. Instead,
it is suggested that increased pulse pressure in the brain capillaries maintains
the ventricular enlargement in chronic hydrocephalus. Chronic hydrocephalus is
due to decreased intracranial compliance, causing restricted arterial pulsations
and increased capillary pulsations. The terms "restricted arterial pulsation
hydrocephalus" or "increased capillary pulsation hydrocephalus" can be used to
stress the hydrodynamic origin of both types of chronic hydrocephalus. The new
hydrodynamic theories explain why third ventriculostomy may cure patients with
communicating hydrocephalus, a treatment incompatible with the conventional view.
PMID- 24351248
TI - La lunga attesa: towards a molecular approach to neuroimaging and therapeutics in
Alzheimer's disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
characterised by the gradual onset of dementia. The pathological hallmarks of the
disease are Abeta amyloid plaques, neurofibrillary tangles (NFT), synaptic loss
and reactive gliosis. Current diagnosis of AD is made by clinical,
neuropsychologic, and neuroimaging assessments. Routine structural neuroimaging
evaluation with computed tomography (CT) and magnetic resonance imaging (MRI) is
based on non-specific features such as atrophy, a late feature in the progression
of the disease, hence the crucial importance of developing new approaches for
early and specific recognition at the prodromal stages of AD. Functional
neuroimaging techniques such as functional magnetic resonance imaging (fMRI),
magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and
single photon emission computed tomography (SPECT), possibly in conjuction with
other related Abeta biomarkers in plasma and CSF, could prove to be valuable in
the differential diagnosis of AD, as well as in assessing prognosis. With the
advent of new therapeutic strategies aimed at reducing the Abeta amyloid burden
in the brain, there is increasing interest in the development of MRI contrast
agents and PET and SPECT radioligands that will permit the assessment of Abeta
amyloid burden in vivo. - ma dov'e / la lenta processione di stagioni / che fu
un'alba infinita e senza strade, / dov'e la lunga attesa e qual e il nome / del
vuoto che ci invade. - Eugenio Montale.
PMID- 24351250
TI - Dynamic MR and Quantitative MR Applied to the Study of Intervertebral Disk
Degeneration.
AB - MR and CT demonstrate morphological changes in intervertebral disks. However the
images do not provide an effective means to document interval changes in the disk
due to degeneration, aging or healing. Functional imaging that may assesses the
biomechanical or the biochemical integrity of the disk, may provide a measure of
changes in the disk over time. To study the biomechanical function of the disk,
translation and rotation of spinal vertebrae can be measured with CT or MR as the
spine is subjected to a specific load or torque. Biochemical integrity of the
disk can be assessed by the estimation of the water content from a measurement of
the T2 relaxation time of disk tissue.
PMID- 24351251
TI - Reprint of: SYMPOSIUM ON CEREBROVASCULAR DISEASES. Pathogenesis, Natural History,
and Treatment of Unruptured Intracranial Aneurysms.
AB - Unruptured intracranial aneurysms (UIAs) are a major public health issue. These
lesions have become increasingly recognized in recent years with the advent of
advanced cerebral imaging techniques. Epidemiological evidence from multiple
sources suggests that most intracranial aneurysms do not rupture. Therefore, it
is desirable to identify which UIAs are at greatest risk of rupture when
considering which to repair. It is important to compare size-, site-, and group
specific natural history rates with size-, site-, and age-specific morbidity and
mortality associated with UIA repair because increased natural history risk often
is associated with increased risk of aneurysm repair. Patient age is crucial in
decision making because of its major effect on operative morbidity and mortality;
however, it does not substantially affect natural history. The effect of age is
most notable in patients about 50 years of age and older for open surgery and
about 70 years of age and older for endovascular procedures. In general, rupture
risk is lowest for patients in asymptomatic group 1 (no history of subarachnoid
hemorrhage) with UIAs less than 7 mm in diameter in the anterior circulation.
Surgical morbidity and mortality are most favorable for asymptomatic patients
younger than 50 years who have UIAs less than 24 mm in diameter in the anterior
circulation and no history of ischemic cerebrovascular disease. Endovascular
morbidity and mortality may be less age dependent, and this could favor
endovascular procedures, particularly in patients aged 50 to 70 years. An
important issue is determining immediate vs long-term risk regarding treatment
effectiveness and durability. This issue emphasizes the importance of long-term
follow-up in patients after surgical and endovascular procedures.
PMID- 24351252
TI - Central Nervous System Venous Thrombosis: The Role of CT & MRI. A Review.
AB - The clinical presentation of central nervous system venous thrombosis (CNSVT) is
variable and non specific. Advances in CT and MRI technology have redefined the
role of these 2 modalities in assessing suspected CNSVT. T1, T2, FLAIR and
DWI/ADC (diffusion weighted imaging/apparent diffusion coefficient) MRI (magnetic
resonance imaging) sequences together with a gadolinium enhanced MRV (magnetic
resonance venography) would the imaging of first choice in suspected venous
thrombosis of the central nervous system. Where there are still problems with
identifying the thrombus and this is crucial to the management, a CTV (computed
tomographic venography) should be performed. Catheter angiography would be used
as a last resort or associated with direct thrombolysis. There may be
circumstances where CT may be used as the first choice. There may be
contraindication to MRI such as pacemakers, aneurysms clips etc.
PMID- 24351253
TI - Endovascular therapy for intracranial dural arteriovenous fistulas.
AB - A retrospective study was conducted on 17 consecutive patients with DAVF admitted
to Monash Medical Centre over 12 years. 15 patients, 82.4%, were treated by
endovascular means with the intention to obliterate the fistula. Three of these
patients also had surgery following embolisation. Angiographic cure was achieved
when we have successfully embolised both the arterial and the venous side whether
by penetration of liquid adhesive or packing with coils. Our cure rate of 60%
(95% CI: 37-83%) compare favourably with published results of 50 to 70%. Our
clinical complication rate is 1/15, 6%; and technical complication is1 from 32
embolisation sessions, 3.1%. Endovascular therapy is effective in achieving a
durable angiographic and clinical cure in the treatment of intracranial DAVF.
Both arterial and venous side need to be occluded.
PMID- 24351255
TI - Welcome ISNR.
PMID- 24351254
TI - Follow-Up on Percutaneous Vertebroplasty Using PMMA in Osteoporotic Patients.
AB - We reviewed the follow-up findings of patients who received percutaneous
vertebroplasty, in order to understand the effects of vertebroplasty on following
issues: pain relief, height restoration, wedge deformity correction, kyphosis
correction, and other radiological findings found in follow up studies, such as
new fractures. Generally, the pain relieving effect after vertebroplasty is long
lasting except when new fracture occurred, or presence of other problems that
caused the back pain. Height restoration and wedge deformity correction last for
more than one year. The effect of kyphosis angle correction may vanish one year
after procedure due to occurrence of new fracture in adjacent vertebral bodies.
PMID- 24351256
TI - Early brain spect in patients after minor craniocerebral trauma.
AB - A prospective study made 57 measurements of cerebral blood flow (CBF) by Single
Photon Emission Computed Tomography (SPECT) in post-traumatic patients. The aim
of the investigation was to evaluate CBF in patients after minor craniocerebral
trauma (mCCT) to ascertain the clinicotopographic correlation of the CBF changes,
and to study SPECT in comparison with computed tomography (CT) findings. In
addition, evaluation of the usefulness of SPECT for forensic medicine, assessment
of secondary brain injury by SPECT and the predictive value of hypofrontalism
were performed. A direct correlation was shown between mCCT and the observed CBF
disorders, and between the CBF disorders and clinical symptoms as well as better
SPECT sensitivity in comparison with CT. The usefulness of SPECT for forensic
medicine purposes was also shown. Secondary brain injuries were disclose and the
predictive value of hypofrontalism was confirmed. No correlation between GCS and
CBF changes was found.
PMID- 24351257
TI - Cerebellar lesions in children with tuberous sclerosis complex.
AB - Cerebellar lesions in tuberous sclerosis complex are less frequent than cerebral
findings. We present the magnetic resonance (MR) features of uncommon cerebellar
changes found in a large series of children with tuberous sclerosis complex
(TSC). MR examinations of 73 children (38 males and 35 females) with TSC were
reviewed. Twelve patients with cerebellar lesions were selected. Patients' ages
ranged from 2.5 years to 21.25 (median: 10.6). The number, anatomic location,
signal intensity and contrast enhancement of these lesions were evaluated. MR
studies were performed with a 1.5 T scanner obtaining T1, T2-weighted images and
FLAIR sequences. Gadolinium was administrated in all cases. Cerebellar tubers
were found in 12 patients (16.4%). The total number of cerebellar tubers was 21.
Most cerebellar tubers were hyperintense on T2-weighted and FLAIR images and
slightly hypointense on T1-weighted images. Eleven of these lesions (52.38%)
revealed contrast enhancement. None of cortical cerebral tubers showed contrast
enhancement. Atrophy of seven cerebellar tubers was noticed. The mutation in TSC2
gene was confirmed in eight patients. Cerebellar tubers are uncommon. They were
not found in the absence of cerebral tubers and may associated with parenchymal
volume loss.
PMID- 24351258
TI - Late relapse of pediatric medulloblastoma.
AB - Medulloblastoma (MB), the most common malignant brain tumor of childhood, is
classified according to pathomorphologic characteristics in the group of central
nervous system embryonal tumors, but both its pathogenesis and biologic behavior
remain unknown. In addition, the relationship of MB to other embryonal brain
tumors is debated and response to therapy is difficult to predict. The authors
report an uncommon case of unfavorable late relapse, local as well as distant, in
a 26-year old male patient, who was free of disease and without treatment-related
morbidity for fifteen years after combined therapy for pediatric MB.
PMID- 24351259
TI - MRI findings in patients with hemiparetic cerebral palsy.
AB - Given the more severe and extensive unilateral brain abnormalities in hemiparetic
cerebral palsy (HCP) patients than in other spastic cerebral palsy patients we
focused exclusively on the localization of brain lesions in children with HCP.
The relationship between neuroradiological findings and side of hemiparesis was
investigated in a group of 30 children with HCP. Seventeen boys and 13 girls aged
four to18 years (mean age 9.7+/-4.2 years) were included in this study. Computed
tomography and magnetic resonance imaging examinations were correlated with the
birth histories, obstetrical records and clinical summaries. Of the 30 patients
with HCP, 2 (6.6%) had normal neuroradiological examinations, 20 (66.6%) had
unilateral and eight (26.6%) bilateral brain lesions. A brain lesion on the
contralateral side of hemiparesis was found in 93.3% of the neuroradiological
examinations. The commonest neuroradiological findings in our study were
periventricular leukomalacia (PVL, 80%), atrophy (70%) and porencephalic cyst
(50%). There was a significant relationship between the symptomatic side and
contralateral PVL, atrophy and porencephalic cyst (40%). PVL, atrophy and
porencephalic cyst were significantly concomitant on the same side (46.6%). We
demonstrated for the first time in the literature that PVL, atrophy and
porencephaly are usually observed concomitantly and contralateral to the side of
motor impairement in HCP patients.
PMID- 24351260
TI - Proton magnetic resonance spectroscopy in patients with normal pressure
hydrocephalus.
AB - The objective of this prospective study was the application of proton magnetic
resonance spectroscopy (1HMRS) in patients with normal pressure hydrocephalus
(NPH) to determine the metabolite profile in the white matter next to left
lateral ventricle and to assess the relationship of this profile with Evan's
index. The study included 26 patients with NPH. Diagnosis of NPH was confirmed by
clinical symptoms such as gait disturbance, dementia or urinary incontinence and
CT study with ventricular enlargement. Ratios of NAA/Cr, Cho/Cr, Lac/Cr and mI/Cr
from deep white matter were measured and compared with Evan's index and diameter
of the IIIrd ventricle. Patients with hydrocephalus showed decreased ratios of N
acetylaspartate (NAA)/Cr (creatine), and increased ratios of Lac(lactate)/Cr in
the white matter near the left frontal horn of the lateral ventricle compared
with a well-matched control group. There was no correlation between NAA/Cr,
Ch/Cr, Lac/Cr, mI (myo-Inositol)/Cr and Evan's index. A significant correlation
was found between Lac/Cr and third ventricle diameter. A positive correlation was
noted between Cho/Cr and dementia in patients with NPH. Our preliminary results
of 1 H MRS support the idea that NPH is associated with white matter ischemia.
Proton MRS is a very useful tool for evaluating major changes in metabolic levels
in deep white matter in NPH patients.
PMID- 24351261
TI - Magnetic Resonance Imaging in a Case of Wernicke's Encephalopathy with
Hyperemesis Gravidarum. A Case Report.
AB - We describe a 29-year-old pregnant woman presenting with neurological signs and
diagnosed to have Wernicke's encephalopathy. The patient had a full recovery
after prompt intravenous thiamine therapy. The clinical, pathological and MR
features of Wernicke's encephalopathy are discussed.
PMID- 24351262
TI - Isolated unilateral cerebellar hypoplasia. A case report.
AB - Isolated cerebellar malformations are relatively rare CNS anomalies, when they do
occur they are frequently symptomatic. Some cases of asymptomatic cerebellar
malformations have been reported. Unilateral cerebellar hypoplasia is one such
entity. We describe a case of unilateral cerebellar hypoplasia presenting with
non-specific neurological complaints.
PMID- 24351263
TI - Thrombotic Thrombocytopenic Purpura with Reversible Neurological Features: Brain
Diffusion MRI with ADC Map, Spect and EEG Findings. A Case Report.
AB - Although nervous system involvement is common in thrombotic thrombocytopenic
purpura (TTP), abnormalities on computerized tomography, magnetic resonance
imaging and electroencephalography are not encountered so frequently and if
present, these abnormalities are often reversible. We describe a 39-year-old
woman with recurring transient focal neurological findings found to have
laboratory findings consistent with TTP. In cerebral diffusion weighted images
(DWI), diffuse cortical hyperintensity was noted in right frontal lobe, but the
ADC (apparent diffusion coefficient) map was normal. Electroencephalography
demonstrated lateralized slowing and repeated DWI showed diffuse cortical
hyperintensity in the right hemisphere. SPECT showed luxury perfusion in the
right hemisphere areas. The patient's condition resolved with plasmapheresis. Our
patient illustrates that diffuse hemispheric involvement can be seen in DWI and
EEG, and SPECT may show luxury perfusion after resolution of neurological
findings in TTP cases. To our knowledge, this is the first TTP case in which the
ADC map was normal.
PMID- 24351264
TI - Choroid plexus papillary carcinoma associated with hemorrhage. A case report.
AB - Choroid plexus papillary carcinoma is a rare intracranial malignant epithelial
tumor. We describe a case of choroid plexus tumor arising in the periventricular
parenchyma. A 52-year-old man presented with headache for five months, aggravated
by vomiting for three days. Brain computed tomography scan revealed an
inhomogeneous density lesion in the right temporoparietal lobe with mild
enhancement, and hemorrhage anterior to the lesion. Histological and
immunohistochemical findings indicated a choroid plexus papillary carcinoma.
PMID- 24351265
TI - Falx Cerebri Ossification: CT and MRI Evaluation.
AB - During the last three years, CT and MRI brain scans of 40 patients revealed falx
cerebri partial ossification as an incidental finding. The patients had been
admitted for brain CT and MRI for several reasons. In most cases, there was no
problem in the differential diagnosis of falx cerebri ossification during
interpretation of the cases. In a few cases, the lesion should be distinguished
from calcified meningioma, small hematoma in the interhemispheric fissure and in
one case there was also meningeal infiltration of breast cancer. In these cases
both CT and MRI scans of the brain were evaluated and a definite diagnosis was
made.
PMID- 24351266
TI - Agenesis of the internal carotid artery and hypogenesis of the pituitary gland:
cause, consequence or coincidence?
AB - The CT and MR imaging findings in a case of unilateral agenesis of the internal
carotid artery and hypogenesis of the pituitary gland are described in a child
with congenital hypopituitarism. The embryological pathogenesis is discussed.
PMID- 24351267
TI - Historia magistra vitae (Cic. De or. 2.36). The Prime Objective of Radiosurgery
in Acoustic Neurinomas.
AB - The central question of stereotaxic radiosurgery in acoustic neurinomas is how to
pinpoint its main objective: is it a better alternative to neurosurgery or an
option when surgery is unfeasible? This study is a continuation of the article
published in 1995 in Acta Neurochirurgica, but benefits from greater experience,
more complete analysis and longer supervision of results. The conclusions that
can be drawn to date from our own findings and from others in the literature are
the following: radiosurgery can be used not only to prevent neurinoma growth and
at the same time to preserve the patient's neurological conditions without the
risk of complications, but it can also be counted on to provide a cure. However,
radiosurgery as an excising device is more insidious than the microsurgical
scalpel, since the narrow beam of radiation, directed to a limited target without
opening the skull, is invisible. The expression coined by Lars Leksell regarded
precisely the innovation he himself conceived in the 'closed skull operation',
with reference to its use in cases of acoustic neurinoma as an alternative to
traditional surgery. Hence, whatever technique or instruments are involved, it is
always a question of interventional neuroradiology or minimally invasive
neurosurgery.
PMID- 24351268
TI - Carotid body paraganglioma. Diagnosis and treatment by angiography.
AB - Paraganglioma is a rare neoplasia of neural crest origin. It most commonly arises
in carotid body, jugular bulb, tympanic plexus on the promontory, and along the
vagal nerve pathway or anywhere along the paraganglia pathway. This review
describes our experience of cervical paraganglioma. Although there is no
consensus in the literature on preoperative angiographic embolization, we think
angiography is the gold standard in the diagnosis and treatment of paraganglioma.
A small paraganglioma probably does not usually require preoperative embolization
because the risks may exceed the benefits. But angiography is mandatory in the
diagnosis and treatment of large highly vascular paragangliomas. Imaging of the
vascular map of the tumor, that is only possible by angiography, will help the
neurosurgeon evaluate the real extension of the neoplasia and chose treatment
modalities. Embolization is performed to decrease operative bleeding, shorten the
surgery timing and avoid cranial nerve deficit. Cemal Umit Isik et al. studied
four brothers with familial paragangliomas noting unexplained concomitant thyroid
functional disorders in their patients. Because of the pedigree they thought this
may have been a coincidence. Our reported case, unrelated to the Turkish family,
also had hypothyroidism suggesting that the relation between paraganglioma and
thyroid dysfunction may not be merely a coincidence.
PMID- 24351269
TI - Emergency Use of Stent and rtPA with Mechanical Cloth Defragmentation for a
Thromboembolic Complication during GDC Coil Treatment of an Acutely Ruptured
Basilar Tip Aneurysm.
AB - Thrombotic occlusion of both posterior cerebral arteries occurred during
embolization of an acutely ruptured basilar tip aneurysm. Intracranial stenting
and continuous superselective infusion of rtPA was administered combined with
mechanical clot fragmentation to reestablish normal vessel flow. DSA disclosed
that normal vessel patency was achieved within 30 min. There were no adverse
events related to rtPA administration and the patient recovered from the
embolization with minor neurologic deficit as present before the procedure.
PMID- 24351270
TI - Fat saturation technique and gadolinium in MRI of lumbar spinal degenerative
disease.
AB - We evaluated the potential of MR sequences with Fat Saturation and gadolinium in
patients with degenerative disease of the lumbar spine and low back pain, by
studying both anterior and posterior elements of the lumbar spine. We examined
3323 patients (age range 15-78 years) presenting low back pain. We used T2
weighted sequences with Fat Saturation and in some selected cases (1063 patients,
32%) administered gadolinium using T1-weighted sequences with Fat Saturation. In
particular we used gadolinium in the following cases: 1) presence of hyperintense
areas on T2 weighted images with Fat Saturation in the osteo-articular and
muscular-ligamentous structures of the lumbar spine; 2) Clinical-radiological
discrepancy in patients without disc-root conflict and clinical suspicion of
posterior vertebral compartment syndrome. We found degenerative-inflammatory
changes in osteo-articular, ligamentous and muscular structures in 1063 patients:
osteochondrosis, "aseptic discitis", facet joint effusion and synovitis,
osteoarthritis, synovial cysts, spondylolysis, degenerative-inflammatory changes
of the posterior ligaments (flava, interspinous and supraspinous ligaments) and
posterior perispinal muscles. To improve diagnostic accuracy and allow correct
therapeutic guidance, MR examination in patients with low back pain must evaluate
both anterior and posterior elements of the lumbar spine. Our study indicates
that T2 sequences with Fat Saturation and, in selected cases, gadolinium
administration, better visualize or disclose degenerative-inflammatory changes in
the lumbar spine, showing the active-inflammatory phase and extension of these
processes which may not be depicted during a standard MR examination.
PMID- 24351271
TI - Primary neurocytoma in the spinal cord. A case report.
AB - Central neurocytoma is defined as an intraventricular benign brain tumor.
Extraventricular location of central neurocytoma is rare: only nine cases of
spinal neurocytoma had been reported in the English literature. We hereby present
a case of atypical neurocytoma involving unusual long segments (8-segment) of
cervico-thoracic spinal cord in a 29-year-old woman with emphasis on pre- and
post-surgical neuroimaging, pathological correlation, and review the pertinent
literature.
PMID- 24351272
TI - Traumatic Nerve Root Avulsion and Pseudomeningocele Diagnosed by Three
Dimensional MRI Technique (CISS Sequence). A Case Report.
AB - This case report demonstrates the importance of the CISS sequence, a fast imaging
technique in MRI, in case of suspected nerve root avulsion. We present a case of
traumatic pseudomeningoceles at T1-T2 root levels with right T2 ventral root
avulsion without associated skeletal fracture diagnosed by MRI using the three
dimensional CISS technique. A 28-year-old man presented to the Emergency
Department following a motorcycle accident. Clinical examination revealed paresis
in intrinsic muscles of the right hand. Traumatic pseudomeningoceles at T1-T2
root levels bilaterally with right T2 ventral root avulsion without associated
skeletal fracture were diagnosed by three dimensional cervicothoracic MRI with
CISS technique.
PMID- 24351273
TI - AINR - News letters. 8th AINR Congress of Pediatric Neuroradiology.
PMID- 24351274
TI - An adaptive genetic algorithm for crystal structure prediction.
AB - We present a genetic algorithm (GA) for structural search that combines the speed
of structure exploration by classical potentials with the accuracy of density
functional theory (DFT) calculations in an adaptive and iterative way. This
strategy increases the efficiency of the DFT-based GA by several orders of
magnitude. This gain allows a considerable increase in the size and complexity of
systems that can be studied by first principles. The performance of the method is
illustrated by successful structure identifications of complex binary and ternary
intermetallic compounds with 36 and 54 atoms per cell, respectively. The
discovery of a multi-TPa Mg-silicate phase with unit cell containing up to 56
atoms is also reported. Such a phase is likely to be an essential component of
terrestrial exoplanetary mantles.
PMID- 24351275
TI - Numerical simulation of diffusion MRI signals using an adaptive time-stepping
method.
AB - The effect on the MRI signal of water diffusion in biological tissues in the
presence of applied magnetic field gradient pulses can be modelled by a multiple
compartment Bloch-Torrey partial differential equation. We present a method for
the numerical solution of this equation by coupling a standard Cartesian spatial
discretization with an adaptive time discretization. The time discretization is
done using the explicit Runge-Kutta-Chebyshev method, which is more efficient
than the forward Euler time discretization for diffusive-type problems. We use
this approach to simulate the diffusion MRI signal from the extra-cylindrical
compartment in a tissue model of the brain gray matter consisting of cylindrical
and spherical cells and illustrate the effect of cell membrane permeability.
PMID- 24351277
TI - Reduced neck-shoulder muscle strength and aerobic power together with increased
pericranial tenderness are associated with tension-type headache in girls: A case
control study.
AB - BACKGROUND: Tension-type headaches (TTH) are common among children worldwide and
mean a potential risk of disability and medication overuse headache. The
associated mechanisms, however, remain unsolved. Our study investigated muscle
strength in the neck-shoulder region, aerobic power and pericranial tenderness in
girls with TTH compared with healthy controls. METHODS: A blinded case-control
study comprising 41 girls with TTH and 41 age-matched healthy controls.
Standardised testing of isometric maximal voluntary contraction (MVC) and force
steadiness of neck flexion and extension, as well as MVC and rate-of-force
development of dominant shoulder, was conducted. VO2 max was recorded by a
submaximal ergometer test and pericranial tenderness by standardised manual
palpation. Logistic regression analyses were applied. RESULTS: Girls with TTH
demonstrated significantly higher pericranial tenderness than controls, in
correlation with headache frequency (r = 0.66, p < 0.001). Results indicated that
the odds ratio of girls having headache are 7.6 (95% CI 1.4-40.9) for weak to
strong shoulder muscles; weak to average neck-shoulder strength OR 3.1 (95% CI
1.2-8.1); neck flexion strength OR 1.3 (95% CI 1.0-1.6) and 5.2 (95% CI: 1.4
19.6) for each unit of decrease in VO2 max. CONCLUSIONS: Reduced neck-shoulder
strength and aerobic power together with increased pericranial tenderness are
associated with TTH in girls. Future interventions should be directed towards
health promoting patient educational programmes on enhanced physical exercising.
Much more exact and detailed research in young girls and boys are needed.
PMID- 24351276
TI - A central role for dityrosine crosslinking of Amyloid-beta in Alzheimer's
disease.
AB - BACKGROUND: Alzheimer's disease (AD) is characterized by the deposition of
insoluble amyloid plaques in the neuropil composed of highly stable, self
assembled Amyloid-beta (Abeta) fibrils. Copper has been implicated to play a role
in Alzheimer's disease. Dimers of Abeta have been isolated from AD brain and have
been shown to be neurotoxic. RESULTS: We have investigated the formation of
dityrosine cross-links in Abeta42 formed by covalent ortho-ortho coupling of two
tyrosine residues under conditions of oxidative stress with elevated copper and
shown that dityrosine can be formed in vitro in Abeta oligomers and fibrils and
that these links further stabilize the fibrils. Dityrosine crosslinking was
present in internalized Abeta in cell cultures treated with oligomeric Abeta42
using a specific antibody for dityrosine by immunogold labeling transmission
electron microscopy. Results also revealed the prevalence of dityrosine
crosslinks in amyloid plaques in brain tissue and in cerebrospinal fluid from AD
patients. CONCLUSIONS: Abeta dimers may be stabilized by dityrosine crosslinking.
These results indicate that dityrosine cross-links may play an important role in
the pathogenesis of Alzheimer's disease and can be generated by reactive oxygen
species catalyzed by Cu2+ ions. The observation of increased Abeta and dityrosine
in CSF from AD patients suggests that this could be used as a potential biomarker
of oxidative stress in AD.
PMID- 24351278
TI - Prolactinoma-associated headache and dopamine agonist treatment.
AB - AIM: The aim of this article is to investigate the phenotype and etiology of
prolactinoma-associated headache as well as present and discuss the plausible
pain-relieving effect of dopamine agonist treatment. METHODS: In this case-based
audit we included 11 patients with prolactinomas and one patient with idiopathic
hyperprolactinemia presenting with headache that subsequently improved or
resolved after dopamine agonist treatment. RESULTS: A significant ipsilateral
location of tumor mass and reported headache symptoms was observed (p = 0.018).
After dopamine agonist treatment seven out of 12 patients became pain free within
2.5 months; after one year of treatment 11 out of 12 reported headache
improvement or resolution. Average tumor volume reduction after treatment was 47
+/- 22% during 9.5 +/- 8.4 months of follow-up. There was no significant
association between headache relief and tumor shrinkage (p = 0.43) or
normalization of serum prolactin (p = 1.00), respectively. CONCLUSIONS: 1) The
significant association between lateralization of tumor and headache suggests a
mechanical origin of the headache, 2) headache responded to dopamine agonist
treatment in most patients, and 3) our observations encourage future prospective
controlled trials to investigate the role of hyperprolactinemia in the
pathogenesis of headache as well as the therapeutic effects of dopamine agonists.
PMID- 24351280
TI - Diet and cancer among Chinese in singapore.
AB - Cancer statistics provided by the Singapore Cancer Registry and a series of diet
related studies carried out in Singapore since 1985 were reviewed. Incidence
rates for cancers in various Chinese populations are compared. In terms of
Singaporean diet a possible protective effect of soyabean products against female
breast cancer is highlighted.
PMID- 24351279
TI - Hypertrophic pachymeningitis associated with cerebral spinal fluid hypovolemia as
initial presentation of systemic lupus erythematous.
AB - We report a case of a 61-year-old man with thickening of the dura mater
associated with the presence of subdural collections as a consequence of cerebral
spinal fluid hypovolemia (CSFH) and hypertrophic pachymeningitis (HP) as
presentation of systemic lupus erythematous (SLE). The patient complained about
fatigue, musculoskeletal pain, headache and skin lesions. In the laboratory tests
minimal normocytic anemia, mild leukopenia, polyclonal hypergammaglobulinemia and
antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (dsDNA),
antibodies against extractable nuclear antigens (ENA) type SSA-Ro, anti-Smith
antigen antibodies (anti-Sm) and anti-ribonucleoprotein antibodies (anti-RNP)
were detected. Cranial magnetic resonance imaging (MRI), with and without
gadolinium enhancement, revealed generalized thickening of the dura mater more
severe at the right parieto-occipital lobes with the presence of subdural
collections. The patient was diagnosed with SLE associated both with CSFH and HP.
A conservative treatment with prednisone 60 mg daily, mycophenolate mofetil (MMF)
1 g daily and hydroxychloroquine 200 mg twice a day was started with significant
clinical and radiological improvement (almost complete resolution of the subdural
collections and clear decrease of meningeal thickness). The authors emphasize
that HP associated with CSFH in the context of SLE is a rare entity, which makes
this case unique.
PMID- 24351281
TI - Assessing food and health relationships: a case study of blood pressure
determination in adult Melbourne Chinese.
AB - An effective public health approach to cardiovascular disease prevention should
be one which gives the general public alternatives in choice when fat, salt and
sugar are reduced in the diet. Fat, salt and sugar are nutrients which can be
found in various foods. Public health educators convert these nutrients into
foods so that the general public can engage in daily food choice. The usual
nutrient-to-food conversion is indirect and can be misleading. For example, we
are still unclear as to the potential benefit of polyunsaturated margarine over
butter or olive oil. In a base-line data analysis of Chinese adults in Melbourne,
we related food intake in addition to nutrients to major cardiovascular risk
factors. In all models, food intake accounted for a higher variation of major
cardiovascular risk factors than did nutrient intake. Melbourne Chinese, who
consumed a wide variety of foods and ate more fish, vegetable, and fruits, had a
better cardiovascular risk profile. The findings are of importance in public
health significance. Longitudinal documentation of changing food intake, in
addition to nutrients, and associated change in cardiovascular risk factors in
this population are needed at this stage followed by further work to confirm its
generalizability to Australians at large. This report focuses on findings of
blood pressure determination in 547 adult Melbourne Chinese and reviews the way
in which food and health relationships may be studied.
PMID- 24351282
TI - Dietary transition in China and its health consequences.
AB - The pattern of food consumption in China has been subject to significant changes
during the last 30-40 years, although the average dietary pattern is still based
on plant foods. These changes have been characterized by increased consumption of
animal products and decreased consumption of cereal products. These trends are
supported by both national food disappearance records and by household survey
data on the intake of specific foods. Changes in urban areas have been much more
substantial than in rural areas. Preliminary findings show that the dietary
transition is associated with a simultaneous decrease in the prevalence of acute
communicable diseases and an increase in the prevalence of the major chronic
degenerative diseases, such as cancers and cardiovascular diseases.
PMID- 24351283
TI - The relationship between dietary factors and serum lipids in southern Chinese
population samples.
AB - As part of the PRC-USA collaborative research project on the epidemiology of
cardiovascular disease, baseline surveys were conducted in four random urban and
rural samples in Guangzhou, Guangdong Province in southern China on 334 men and
women aged 35-54 in the fall of 1983-84 with the aim of studying the correlation
between dietary intakes and serum lipids. Methods standardized by the US Centers
for Disease Control were used for measuring different parameters, and quality
control was emphasized to assure comparability between workers and farmers. Three
24-hour recalls were collected from each participant in each survey. Mean values
of daily intakes of nutrients per capita for the four groups were as follows: 59
69% kcal carbohydrate; 10-12% kcal protein; 22-26% kcal fat. Dietary total fat,
saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA) and cholesterol
were higher in the urban than the rural areas. Mean levels of serum total
cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL
C) and low density lipoprotein cholesterol (LDL-C) were 4.6 mmol/l, 1.1 mmol/l,
1.3 mmol/l and 2.8 mmol/l respectively. The TC, TG and LDL-C and HDL-C were
significantly higher in the urban than the rural areas. Analyses of correlation
showed that the Keys 'dietary lipid score' was positively associated with TC, LDL
C and HDL-C; specifically, dietary cholesterol was positively associated with
serum TC. Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) were
positively correlated with HDL-C. It seems that the traditional dietary pattern
of Guangzhou favours serum lipids being at an optimal level.
PMID- 24351284
TI - Cross-cultural comparisons between Taipei Chinese and Framingham Americans:
dietary intakes, blood lipids and apolipoproteins.
AB - Dietary intakes (24-hour recall), total cholesterol (TC), triglyceride (TG), low
density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol
(HDL-C), apolipoprotein (apo) A-l and apo B were assessed in healthy middle-aged
subjects in Taipei, and in sex-age-menopause matched subjects in the Framingham
Heart Study. Taipei subjects consumed a diet consisting of 16%, 48%, 35% and 1%
of calories from protein, carbohydrate, fat, and alcohol, vs 17%, 40%, 39%, and
4% in Framingham subjects, respectively. The saturated, monounsaturated, and
polyunsaturated fatty acid content of the diet was estimated to be 9%, 13%, and
13% of total calories in Taipei subjects and 16%, 15%, and 8% in Framingham
subjects, respectively. The differences between Taipei and Framingham subjects
were quite substantial for lipid parameters but less so for apolipoprotein
levels. Gender differences for TG, HDL C, apo A-l, and apo B were more profound
than differences due to nationality. Taipei male and female subjects had
significantly lower TC, LDL-C, and significantly higher HDL C concentrations than
Framingham male and female subjects. After adjusting for body mass index (BMI),
TC and LDL C levels remained significantly different for both sexes between
populations, probably attributable to differences in saturated fat intake. This
study documents that urban workers in Taipei consumed a diet with a relatively
high polyunsaturated and low saturated content and had more favorable lipid
profiles than Framingham Americans.
PMID- 24351285
TI - Serum cholesterol and dietary fat of two populations of southern Chinese.
AB - Children in Hong Kong (HK) are the second generation of Chinese migrants from
Guangdong Province and are leading a more affluent lifestyle than those in
Jiangmen (JM). The association between affluence and coronary risk was
investigated by comparing the serum cholesterol and dietary fat intake of
children in HK and JM. Fasting serum cholesterol was examined in 94 HK children
and 99 JM children, all aged seven, using the same enzymatic method by the same
observer. Duplicate meals were collected in two subsamples of 20 children, one
each from HK and JM and analysed for their total fat intake and fatty acid
profile, again by the same observer using gravimetric methodology and gas
chromatography. The mean (SD) cholesterol of HK children was 4.59 (0.83) mmol/l,
significantly higher than that of JM, 4.16 (0.61) mmol/l. The daily fat intake by
the HK children was 48 g, 37% higher than that of JM at 35 g. PS ratio was 0.6in
HK and 0.8 in JM. Cl8-2/C14-0, the cholesterol-lowering ratio, was mostly below
10 in HK, whereas that of JM was between 10 and 40 Therefore, in order to lower
the total serum cholesterol of Hong Kong children, dietary intervention to lessen
total fat, in particular milk and animal fat, while moderately increasing fat
consumption from vegetable sources would seem to be appropriate.
PMID- 24351286
TI - Body composition of Chinese compared with data from North America.
AB - A multiple tracer dilution method measuring total body water (TBW) and extra
cellular water (ECW) was used to study body composition. Healthy Chinese were
compared to a group of healthy Americans evaluated by similar dilutional methods.
Compared to the American subjects, Chinese subjects were less heavy (body weight
was 62.1 +/- 2.0 kg vs 72.5+/- 4. 1, P<0.05), leaner (body fat was 19.6 +/- 1.8%
of body weight vs 25.8 +/- 1.9, P<0.005), wetter (total body water was 58.9 +/-
1.3% vs 54.3 +/- 1.4, P<0.005) and had a greater percentage of body cell mass
(50.9 +/- 1.7% vs 44.2 +/- 1.4, P<0.001). The multidilution method using
deuterium oxide and sodium bromide to assess body composition is accurate but
expensive and laborious. Therefore, equally precise but more economical bedside
methods are needed for routine compositional analysis.
PMID- 24351287
TI - Dietary habits, physical activity and body size among Chinese in North America
and China.
AB - We examined the self-reported dietary nutrient intakes, physical activity
patterns and body mass index (BMI) of 2488 healthy Chinese men and women residing
in North America (and Canada) and in the People's Republic of China. On average,
Chinese in China consumed more total energy (males 3024 kcal in China, vs 2122
kcal in North America; females 2351 kcal in China. vs 1745 kcal in North America)
and carbohydrate but less fat (males 74.s g in China vs 82.0 g in North America,
females 56.0 g in China vs 68.8 g in North America), protein, vitamin A, b
carotene and vitamin C than did Chinese in North America. Dietary fat provided
35% of total dietary energy for Chinese in North America and 22% for Chinese in
China. Consumption of alcohol, particularly wine and hard liquor, was higher
among Chinese in China than Chinese in North America. Chinese in China reported
more kilocalories of energy expenditure per day, especially in vigorous activity
and walking, than Chinese in North America. Chinese in China weighed less and
were leaner than North American Chinese. These differences in nutrient intakes,
physical activity and body size of Chinese living in two different continents
suggest possible explanations for observed differences in chronic disease rates
in the two populations.
PMID- 24351289
TI - SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors
by orchestrating HIF-1alpha-dependent glycolysis.
AB - Myeloid-derived suppressor cells (MDSC) display an immature phenotype that may
assume a classically activated (M1) or alternatively activated phenotype (M2) in
tumors. In this study, we investigated metabolic mechanisms underlying the
differentiation of MDSCs into M1 or M2 myeloid lineage and their effect on cancer
pathophysiology. We found that SIRT1 deficiency in MDSCs directs a specific
switch to M1 lineage when cells enter the periphery from bone marrow, decreasing
the suppressive function in favor of a proinflammatory M1 phenotype associated
with tumor cell attack. Glycolytic activation through the mTOR-hypoxia-inducible
factor-1alpha (HIF-1alpha) pathway was required for differentiation to the M1
phenotype, which conferred protection against tumors. Our results define the
essential nature of a SIRT1-mTOR/HIF-1alpha glycolytic pathway in determining
MDSC differentiation, with implications for metabolic reprogramming as a cancer
therapeutic approach.
PMID- 24351288
TI - Activation of the NOTCH pathway in head and neck cancer.
AB - NOTCH1 mutations have been reported to occur in 10% to 15% of head and neck
squamous cell carcinomas (HNSCC). To determine the significance of these
mutations, we embarked upon a comprehensive study of NOTCH signaling in a cohort
of 44 HNSCC tumors and 25 normal mucosal samples through a set of expression,
copy number, methylation, and mutation analyses. Copy number increases were
identified in NOTCH pathway genes, including the NOTCH ligand JAG1. Gene set
analysis defined a differential expression of the NOTCH signaling pathway in
HNSCC relative to normal tissues. Analysis of individual pathway-related genes
revealed overexpression of ligands JAG1 and JAG2 and receptor NOTCH3. In 32% of
the HNSCC examined, activation of the downstream NOTCH effectors HES1/HEY1 was
documented. Notably, exomic sequencing identified 5 novel inactivating NOTCH1
mutations in 4 of the 37 tumors analyzed, with none of these tumors exhibiting
HES1/HEY1 overexpression. Our results revealed a bimodal pattern of NOTCH pathway
alterations in HNSCC, with a smaller subset exhibiting inactivating NOTCH1
receptor mutations but a larger subset exhibiting other NOTCH1 pathway
alterations, including increases in expression or gene copy number of the
receptor or ligands as well as downstream pathway activation. Our results imply
that therapies that target the NOTCH pathway may be more widely suitable for
HNSCC treatment than appreciated currently.
PMID- 24351290
TI - Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma
growth.
AB - The relevance of cysteine metabolism in cancer has gained considerable interest
in recent years, largely focusing on its role in generating the antioxidant
glutathione. Through metabolomic profiling using a combination of high-throughput
liquid and gas chromatography-based mass spectrometry on a total of 69 patient
derived glioma specimens, this report documents the discovery of a parallel
pathway involving cysteine catabolism that results in the accumulation of
cysteine sulfinic acid (CSA) in glioblastoma. These studies identified CSA to
rank as one of the top metabolites differentiating glioblastoma from low-grade
glioma. There was strong intratumoral concordance of CSA levels with expression
of its biosynthetic enzyme cysteine dioxygenase 1 (CDO1). Studies designed to
determine the biologic consequence of this metabolic pathway identified its
capacity to inhibit oxidative phosphorylation in glioblastoma cells, which was
determined by decreased cellular respiration, decreased ATP production, and
increased mitochondrial membrane potential following pathway activation. CSA
induced attenuation of oxidative phosphorylation was attributed to inhibition of
the regulatory enzyme pyruvate dehydrogenase. Studies performed in vivo
abrogating the CDO1/CSA axis using a lentiviral-mediated short hairpin RNA
approach resulted in significant tumor growth inhibition in a glioblastoma mouse
model, supporting the potential for this metabolic pathway to serve as a
therapeutic target. Collectively, we identified a novel, targetable metabolic
pathway involving cysteine catabolism contributing to the growth of aggressive
high-grade gliomas. These findings serve as a framework for future investigations
designed to more comprehensively determine the clinical application of this
metabolic pathway and its contributory role in tumorigenesis.
PMID- 24351293
TI - Pneumosinus Dilatans Syndrome of the Sphenoid Sinus. A CT Evaluation.
AB - This study discusses the CT findings of pneumosinus dilatans of the sphenoid
sinus, highlighting the clinically important CT characteristics. The CT findings
of 26 patients with overpneumatization of the sphenoid sinus are presented in
correlation with the clinical findings. Twenty-two patients had
overpneumatization beyond the boundaries of the body of the sphenoid bone with or
without bone remodelling but only two patients reported headaches. Thinning of
the bone structures was also present in three patients but only one patient
reported headaches. Overpneumatization of the sphenoid sinus with thinning of
bunywalls reduced the width of the superior orbital fissure in one patient
resulting in a gradual decrease of visual acuity. CT is an accurate method for
the evaluation of overpneumatization of the sphenoid sinus due to its high
sensitivity in depicting evidence of bone erosion using a bone window as imaging
settings.
PMID- 24351291
TI - FANCJ localization by mismatch repair is vital to maintain genomic integrity
after UV irradiation.
AB - Nucleotide excision repair (NER) is critical for the repair of DNA lesions
induced by UV radiation, but its contribution in replicating cells is less clear.
Here, we show that dual incision by NER endonucleases, including XPF and XPG,
promotes the S-phase accumulation of the BRCA1 and Fanconi anemia-associated DNA
helicase FANCJ to sites of UV-induced damage. FANCJ promotes replication protein
A phosphorylation and the arrest of DNA synthesis following UV irradiation.
Interaction defective mutants of FANCJ reveal that BRCA1 binding is not required
for FANCJ localization, whereas interaction with the mismatch repair (MMR)
protein MLH1 is essential. Correspondingly, we find that FANCJ, its direct
interaction with MLH1, and the MMR protein MSH2 function in a common pathway in
response to UV irradiation. FANCJ-deficient cells are not sensitive to killing by
UV irradiation, yet we find that DNA mutations are significantly enhanced. Thus,
we considered that FANCJ deficiency could be associated with skin cancer. Along
these lines, in melanoma we found several somatic mutations in FANCJ, some of
which were previously identified in hereditary breast cancer and Fanconi anemia.
Given that, mutations in XPF can also lead to Fanconi anemia, we propose
collaborations between Fanconi anemia, NER, and MMR are necessary to initiate
checkpoint activation in replicating human cells to limit genomic instability.
PMID- 24351294
TI - Metabolite Profile in Pyramidal Tracts after Ischemic Brain Stroke Assessed by 1H
MRS. A Multicenter Study.
AB - The magnitude of the motor deficit in patients with stroke depends not only on
the size and location of the destroyed brain tissue, but also on axonal injury in
the descending motor pathways which appears after stroke. After cerebral
ischemia, there are no visible abnormalities in conventional MRI in the intact
pyramidal tracts despite the process of neuronal destruction by Wallerian
degeneration. Conventional MRI is not a sensitive test for Wallerian degeneration
in the acute or subacute time period as it shows no changes within the first four
weeks. Magnetic resonance spectroscopy (MRS) has been used for better
quantification of the extent or severity of fibre damage by evaluating metabolite
alterations in normal-appearing corticospinal and corticopontal tracts. This
study assessed the role of 1H MRS in the detection of changes in cerebral
metabolite levels in pyramidal tracts after cortical/ subcortical infarction and
to compare metabolite alterations to clinical outcome (assessed by Barthel index,
Scandinavian Stroke Scale). The study included 31 patients who had suffered an
ischemic cortical/subcortical stroke involving the motor cortex or the descending
fibers. Ratios of NAA/Cr, Cho/Cr, lip/Cr and Lac/Cr from internal capsules and
cerebral peduncles were measured and compared with clinical status assessed by
Barthel index and Scandinavian Stroke Scale (SSS). The ratio of NAA/Cr was
significantly decreased (p<0.001) in the normal-appearing ipsilateral internal
capsule in comparison with the control group. Cho/Cr and lac/Cr ratios were
increased compared to the control group (p=0.019). Decrease of NAA/Cr ratio
correlated with clinical status assessed by Barthel index and there was a
correlation between clinical improvement (assessed by SSS) and lac/Cr ratio.
Tissue metabolite concentrations distant from the infarcted region correlated
with the clinical course and had predictive value. Proton MRS is very useful tool
for evaluating major changes in metabolite levels in pyramidal tracts after brain
stroke.
PMID- 24351292
TI - Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing
mitochondrial biogenesis.
AB - Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions,
commonly called the "Warburg effect." Aerobic glycolysis often directly
correlates with malignancy, but its purpose, if any, in metastasis remains
unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic
glycolysis decreases and oxidative phosphorylation predominates. However, when
KISS1 is missing the secretion signal peptide (DeltaSS), invasion and metastasis
are no longer suppressed and cells continue to metabolize using aerobic
glycolysis. KISS1-expressing cells have 30% to 50% more mitochondrial mass than
DeltaSS-expressing cells, which are accompanied by correspondingly increased
mitochondrial gene expression and higher expression of PGC1alpha, a master
coactivator that regulates mitochondrial mass and metabolism. PGC1alpha-mediated
downstream pathways (i.e., fatty acid synthesis and beta-oxidation) are
differentially regulated by KISS1, apparently reliant upon direct KISS1
interaction with NRF1, a major transcription factor involved in mitochondrial
biogenesis. Since the downstream effects could be reversed using short hairpin
RNA to KISS1 or PGC1alpha, these data appear to directly connect changes in
mitochondria mass, cellular glucose metabolism, and metastasis.
PMID- 24351295
TI - Comparison of Diffusion-Weighted MR Imaging and T2-Weighted MR Imaging in
Patients with Amyotrophic Lateral Sclerosis.
AB - The purpose of this study was to compare diffusion-weighted MR imaging with
conventional MR sequences in patients with amyotrophic lateral sclerosis (ALS)
and controls, and to assess the diagnostic value of diffusion-weighted imaging in
the ALS patients. Twelve patients with ALS (ten men and two women, mean age 56
years) and 12 age-matched control subjects were studied with axial diffusion
weighted imaging and conventional MR imaging. Three adjacent slices of diffusion
weighted imaging were obtained at the level of the internal capsule. The
diffusion-weighted imaging was performed with a b-value from 165-600 s/mm(2).
Identical slices of diffusion-weighted images and conventional MR images were
evaluated by a consensus reading. Diffusion-weighted images showed high signal
intensity in the corticospinal tract at the level of the internal capsule in
11/12 patients with ALS (92%) and 5/12 control subjects (42%), whereas T2
weighted images (T2WI) revealed high signal intensity in the corticospinal tract
in 11/12 patients with ALS (92%) and 8/12 control subjects (67%). The proton
weighted images (PDWI) disclosed the high signal corticospinal tract in 5/12
patients with ALS (42%), but not in any of the control subjects. Considering ALS
patients versus control subjects, statistical analysis demonstrated that
diffusion-weighted imaging (p=0.027, X(2) test) and proton-weighted imaging
(p=0.037) were more specific than T2-weighted imaging. Diffusion-weighted imaging
and proton-weighted imaging were more specific than T2-weighted imaging. The
combination of diffusion-weighted imaging and T2WI/PDWI seems a promising tool in
the diagnosis of amyotrophic lateral sclerosis.
PMID- 24351296
TI - Non-Inferential Multi-Subject Study of Functional Connectivity during Visual
Stimulation.
AB - Independent component analysis (ICA) is a powerful technique for the
multivariate, non-inferential, data-driven analysis of functional magnetic
resonance imaging (fMRI) data-sets. The non-inferential nature of ICA makes this
a suitable technique for the study of complex mental states whose temporal
evolution would be difficult to describe analytically in terms of classical
statistical regressors. Taking advantage of this feature, ICA can extract a
number of functional connectivity patterns regardless of the task executed by the
subject. The technique is so powerful that functional connectivity patterns can
be derived even when the subject is just resting in the scanner, opening the
opportunity for functional investigation of the human mind at its basal "default"
state, which has been proposed to be altered in several brain disorders. However,
one major drawback of ICA consists in the difficulty of managing its results,
which are not represented by a single functional image as in inferential studies.
This produces the need for a classification of ICA results and exacerbates the
difficulty of obtaining group "averaged" functional connectivity patterns, while
preserving the interpretation of individual differences. Addressing the subject
level variability in the very same framework of "grouping" appears to be a
favourable approach towards the clinical evaluation and application of ICA-based
methodologies. Here we present a novel strategy for group-level ICA analyses,
namely the self-organizing group-level ICA (sog-ICA), which is used on visual
activation fMRI data from a block-design experiment repeated on six subjects. We
propose the sog-ICA as a multi-subject analysis tool for grouping ICA data while
assessing the similarity and variability of the fMRI results of individual
subject decompositions.
PMID- 24351297
TI - Bilateral cerebellar dysplastic gangliocytomas (lhermitte duclos disease) with
cerebellar ectopia and presyrinx cord changes. A case report.
AB - Lhermitte-Duclos disease (LDD) is a rare cerebellar lesion with features of both
malformation and benign neoplasm. However, the fundamental nature of the entity,
its pathogenesis, and the exact genetic alterations remain unknown. We describe a
rare case of bilateral LDD with cerebellar ectopia and presyrinx spinal cord
changes. Bilaterality of lesions should argue against a neoplastic origin and
support a hamartomatous origin.
PMID- 24351298
TI - 3 Tesla MR Study of Cerebellar Medulloblastoma.
AB - Medulloblastoma belongs to the group of highly malignant neuroepithelial tumours
and is the commonest tumour in childhood (average age nine years) followed by
astrocytoma 1. Medulloblastoma usually arises in the posterior fossa, namely the
cerebellar vermis, and more seldom in the fourth ventricle, supratentorium and
spinal cord. We describe the 3 Tesla magnetic resonance (MR) features of a
medulloblastoma located in the right cerebellar hemisphere adhering to the
tentorium in a 16-year-old male.
PMID- 24351299
TI - Delayed symptomatic cyst formation following gamma-knife radiosurgery. A case
report.
AB - We report a case of symptomatic cyst formation as a delayed complication of gamma
knife radiosurgery for treatment of intracranial arteriovenous malformation. The
cyst was discovered six years after GKS. Initially it was asymptomatic,
presenting with symptoms of mass effect after another six months. It was
decompressed by a cystoperitoneal shunt following which the symptoms were
relieved.
PMID- 24351301
TI - Giant intracranial chordoma: neuroradiological and radiotherapeutic aspects.
AB - We describe a rare case of giant intracranial chordoma, emphasizing the patient's
long survival and his excellent response to radiotherapy that led to a
progressive regression of neurological symptomatology up to disappearance, in the
absence of cerebral white matter damages.
PMID- 24351300
TI - Ectopic suprasellar pituitary adenoma. A case report.
AB - The occurrence of a pituitary adenoma located entirely outside the sella turcica,
so-called ectopic adenoma, is extremely rare. We report a case of a non secreting
pituitary adenoma located above the diaphragma sellae, with no invasion into the
sella turcica, confirmed at surgery. The tumor was initially treated
unsuccessfully by operations via the transphenoidal route. After initial negative
exploration by the transphenoidal route, the patient was successfully treated by
an endoscopic endonasal transphenoidal approach extended to the tuberculum sellae
and the posterior planum sphenoidale to access the suprasellar supraglandular
region. A brief review of ectopic adenomas and a discussion of the preoperative
diagnosis are presented.
PMID- 24351302
TI - Hemifacial Spasms and Involuntary Facial Movements. Role of Magnetic Resonance in
the Diagnostic Work-up. A Case Report.
AB - Caution is required when dealing with patients presenting hemifacial spasm as the
symptom is common to many disorders (tumours, herpes zoster, a frigore paralysis,
neurovascular conflict...). Often no reasonable cause of the spasm is found, but
treatment must be attempted because hemifacial spasm can be highly debilitating.
We describe a case of hemifacial spasm, initially deemed idiopathic, in which MRI
demonstrated neurovascular conflict as the cause. It is not always easy to find a
clear MRI pattern, but if the scan identifies the tortuousness of the arteries in
the vicinity of the VII nerve root exit, it is highly probable that this is the
true cause of hemifacial spasm. Even when it is not possible to identify this
pattern, neurovascular compression cannot be ruled out. The good results of
microvascular decompression in patients without a typical MRI pattern suggest
that MRI is specific, but not always sensitive. There is no consensus in the
literature on the sensitivity of MRI in the detection of neurovascular
compression and values vary widely. It is generally believed that experience and
different performance of the MR systems strongly influence the diagnosis of
neurovascular conflict.
PMID- 24351303
TI - A tractography study of a patient with schizencephaly. A pictorial essay.
PMID- 24351304
TI - Supply of medical devices for neuroradiological diagnosis and interventional
procedures: a consignment inventory proposal.
PMID- 24351305
TI - Management of spinal dural arteriovenous fistulae with emphasis on an
endovascular approach.
AB - Spinal arteriovenous shunts are rare and present at a rate of approximately 1:10
with cerebral arteriovenous shunts. Spinal dural arteriovenous fistulas (SDAVF)
are the most common type of spinal vascular malformation in the adult and account
for about 60% of all, with a marked male predominance (5:1). Endovascular
treatment has gained force as the treatment of choice in recent years. We
reviewed the patients sent to our service at Clinica del Rosario in Madrid and
Hospital General de Cataluna in Barcelona between January 1991 and December 2005
with a diagnosis of SDAVF made clinically or by imaging for possible endovascular
treatment. Location, presenting symptoms, and clinical outcome according to
treatment were analyzed. A total of 104 patients were diagnosed and treated for a
SDAVF, 85 were men and 19 women aged between 23 and 79 years (average 58).
Seventy-six were treated with embolization alone (73%), 21 with a combination of
endovascular therapy and surgery (20.1%) and seven patients had surgery alone
(6.7%). Of the embolization group, 62 patients were cured (81.5%), 11 improved
(14.4%) and three (3.9%) worsened. Of the group with combined therapy, 13 (61.9%)
were cured, five (23.8%) improved and three (14.2%) worsened. Among the surgery
group, four (57.2%) were cured and three (42.8%) worsened. Endovascular approach
with liquid adhesive is gaining more acceptance as the treatment of choice for
SDAVF if the conditions allow a super selective catheterization of the shunt.
These patients benefit most when diagnosis is made early in the course of the
pathology and have a better chance of a complete remission of symptoms.
PMID- 24351306
TI - Spontaneous regression of intracranial arteriovenous malformations. A report of
two cases.
AB - Spontaneous and complete regression of cerebral arteriovenous malformations has
rarely been reported in the literature. We describe two new cases with a
literature review.
PMID- 24351307
TI - Posterior fossa arteriovenous pial fistula: diagnostic and endovascular
therapeutic features. A case report.
AB - Intracranial arteriovenous fistulas (AVFs) are rare vascular cerebral lesions
composed of one or more cortical-pial arterial feeders directly connected with a
single draining vein. They differ from the other AV malformations in that they
lack a nidus and are located outside the dural leaflets. Because of high flow and
pressure AVFs have a high risk of hemorrhage and if untreated cause death in up
to 63% of cases. Treatment can be endovascular or microneurosurgical. We describe
an infant with hydrocephalus and raised intracranial pressure and MRI findings of
a single dilated venous vessel with a proximal varix in the perimedullary spaces
confirmed by CT angiography and DSA that found a single artery-single vein
fistula we successfully occluded with GDC coils.
PMID- 24351308
TI - Orbital Cysticercosis: Comparing Multi-Slice CT and Steady State MR to Identify
Scolex.
AB - Orbital cysticercosis with both ocular and extraocular involvement is common in
endemic areas. The presence of scolex is considered diagnostic of cysticercosis.
We sought to compare multi-slice CT and 3D steady state MR in the identification
of scolex in orbital cysticercosis. Three patients with orbital cysticercosis
(two extra-ocular, one ocular) were studied using multi-slice CT with thin
coronal and sagittal reformations and 3D steady state MR (CISS 3D - Constructive
Interference in Steady State) sequence.
PMID- 24351309
TI - Geniculo-temporo-parotideal neurofibroma of the facial nerve. A case report.
AB - Preoperative diagnosis of facial nerve neurofibroma is difficult when it presents
as an asymptomatic parotideal mass. Facial nerve tumor suspicion arises during
parotid surgery, histopathologic evaluation confirms diagnosis and postoperative
imaging demonstrates a nerve tumor and its extension. We present the
multimodality imaging findings of a 43-year-old man with a solitary neurofibroma
involving the whole facial nerve continuously from geniculate ganglion to
parotideal segment as the first case in the literature.
PMID- 24351310
TI - Extracentral nervous system metastases from medulloblastoma. A case report.
AB - Medulloblastoma belongs to the group of highly malignant neuroepithelial tumours
and is the commonest tumour in childhood (12-25 %) (1), but is rare in adults
(0.4-1%) of all primary brain tumours) (1,2). Medulloblastomas usually arise in
the posterior fossa and spread readily throughout the CSF, although 10-30% of
patients develop extracentral nervous system metastases (2). We describe a 30
year-old woman presenting bone metastases from medulloblastoma located
predominantly in the spine.
PMID- 24351311
TI - Letter to the editor. A case of inborn choroid plexus carcinoma.
AB - This is a short comment on the article by Balaji et al. "CT and MR Imaging in
Choroid Plexus Carcinoma. Report of Two Cases" (The Neuroradiology Journal 2006,
19: 330-333).
PMID- 24351313
TI - ISNR - Newsletter. 9th Annual Conference of the Indian Society of Neuroradiology
Guwahati 17-19 November 2006.
PMID- 24351312
TI - The 55th italian neurosurgery congress and the latest on radiosurgery.
AB - "...It is still too early for a critical evaluation of ventriculography or
encephalography as a diagnostic aid in tumours of the brain and syndromes related
to them. For this, considerably more experience is required than we possess at
present, experience based, if possible, on material observed and treated in a
uniform manner..." - Olivecrona 1927, quoted by Lysholm.
PMID- 24351314
TI - Assessment of myocardial adrenergic innervation with a solid-state dedicated
cardiac cadmium-zinc-telluride camera: first clinical experience.
AB - AIMS: To investigate the relationships between regional adrenergic innervation
heterogeneity, myocardial perfusion, and contractile function obtained by means
of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated
camera. METHODS: Twenty-eight patients with or without ischaemic heart disease
underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT
early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with
a single-day protocol. The heart-to-mediastinum ratio and the washout rate were
computed from planar (123)I-MIBG images. The summed (123)I-MIBG defect scores (SS
MIBG) were semi-quantitatively assessed from CZT images. The summed rest score
(SRS), summed motion score (SMS), and summed thickening score (STS) were
quantitated from (99m)Tc-tetrofosmin images. RESULTS: Sixteen patients showed a
depressed left ventricular systolic function [ejection fraction (EF)<50%]. They
presented higher SRS (P = 0.007), SMS (P < 0.001), STS (P < 0.001), and early SS
MIBG (P = 0.007) values than those with normal contractile function.
Interestingly, higher early SS-MIBG values, index of regional sympathetic
innervation heterogeneity, clustered with more elevated SRS (P = 0.023), and more
impaired measures of regional and global left ventricle systolic function, i.e.
SMS (P = 0.046), STS (P = 0.014), and EF (P = 0.027). At multivariate analysis, a
higher SRS (P = 0.039) remained the only independent predictor of more elevated
early SS-MIBG values. In the 20 of 28 ischaemic patients, the correlations
between early SS-MIBG and SMS (P = 0.017) and also STS (P = 0.036) were further
confirmed. The effective dose of the investigation was 4.2 +/- 0.72 mSv.
CONCLUSIONS: An altered early SS-MIBG, assessed with a low-dose imaging protocol
and a CZT cardiac camera, identifies patients with more impaired myocardial
perfusion and contractile function.
PMID- 24351315
TI - Case suitability for definitive through knee amputation following lower extremity
blast trauma: analysis of 146 combat casualties, 2008-2010.
AB - INTRODUCTION: Analysis of recent UK Armed Forces combat casualty data has
highlighted a significant number of through joint traumatic amputations (TAs),
most commonly through knee (through knee amputations (TKAs)). Previously, a
consensus statement on lower limb amputation from the UK Defence Medical Services
reported better outcomes in some patients with TKAs when compared with those with
above knee amputations. This study sought to define the proportion of recent
combat casualties sustaining severe lower extremity trauma with acute osseous and
soft tissue injury anatomy amenable to definitive TKA. METHODS: The UK Joint
Theatre Trauma Registry and post mortem CT (PM-CT) databases were used to
identify all UK Armed Forces personnel (survivors and fatalities) sustaining a
major extremity TA (through/proximal to wrist or ankle joint) between August 2008
and August 2010. Through knee and all below knee TAs were grouped as 'potential
TKAs' (pTKAs), that is, possible candidates for definitive TKA. RESULTS: 146
Cases (75 survivors and 71 fatalities) sustaining 271 TAs (130 in survivors, 141
in fatalities) were identified. The through-joint TA rate was 47/271 (17.3%);
34/47 through-joint injuries (72.3%) were TKAs. Overall, 63/130 TAs in survivors
and 66/140 TAs in fatalities merited analysis as the pTKA group. Detailed
anatomical data on pre-debridement osseous and soft tissue injury levels were
only consistently available for fatalities through PM-CT findings. Further
analysis of the soft tissue injury profile revealed that a definitive TKA in the
pTKA group (all BKAs as well as TKAs) would have been proximal to the zone of
injury (ZOI) in only 3/66 cases. CONCLUSIONS: Traumatic TKAs following explosive
blast are more common than previously reported. The majority of lower limb TAs
are skeletally amenable to a definitive TKA. Maximising residual stump length
carries the risks of definitive level amputation within the original ZOI but this
study demonstrates that the proximal extent of the soft tissue injury may
frequently make this unavoidable. Further work is required to determine the
relative merits of definitive below, through and above knee amputations in the
short, medium and long term to ensure survivors are subject to minimal
complications while maintaining capacity to achieve optimal functional outcomes.
PMID- 24351316
TI - Translational toxicological research: investigating and preventing acute lung
injury in organophosphorus insecticide poisoning.
AB - Poisoning through ingestion of organophosphorus (OP) insecticide is a leading
cause of suicide globally. Severe poisoning with OP compounds creates an
unconscious, paralysed patient with respiratory failure. These symptoms make
pulmonary aspiration of stomach contents highly likely, potentially causing an
acute lung injury. To explore this hypothesis, we created a Gottingen minipig
pulmonary aspiration model (n=26) to investigate the mechanism and severity of
lung injury created through pulmonary instillation of 0.5 mL/kg mixtures of
porcine gastric juice (GJ), OP and/or its solvent. Early results show that
aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar
haemorrhage and interstitial oedema, with disruption of the alveolar-capillary
membrane. Further measurements will include quantitative CT imaging,
histopathology scoring, acute lung injury biomarkers and respiratory function. In
order to test the validity of the minipig model, a pilot study in Sri Lanka has
been devised to observe signs of lung injury in human patients who have ingested
OP insecticide with or without clinical evidence of pulmonary aspiration. Lung
injury will be assessed with PaO2/FIO2 ratios and physiological dead space
measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48 h
after poisoning and at 3-4 h in surgical control patients to measure acute lung
injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012,
showed that over 40% of unconscious poisoned patients with a GCS <9 were not
intubated for ambulance transfer between rural and district hospitals. Delay in
intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of
unconscious poisoned patients. We hypothesise that non-drug assisted placement of
supraglottic airways may be a good tool for use in unconscious poisoned patients
requiring transfer from small rural hospitals in Asia. They could confer better
airway protection than no airway intervention and reduce both morbidity and
mortality.
PMID- 24351317
TI - Rear Operations Group medicine: a pilot study of psychological decompression in a
Rear Operations Group during Operation HERRICK 14.
AB - OBJECTIVES: To investigate group activity psychological decompression (GAPD) in a
Rear Operations Group. METHODS: Provision of military archaeological exercises
for a Rear Operations Group's medical centre patients during Op HERRICK 14 with
analysis of before and after Patient Health Questionnaires (PHQ), Work and Social
Adjustment Scales, generalised anxiety disorder (GAD) 7 Anxiety, Audit
Questionnaire and Impact of Events Scale Revised and analysis of interviews with
supervisors and soldiers. RESULTS: Soldiers reported a mean of 13%-38%
improvement across the self-reported domains. The civilian archaeologists
reported improvements in self-esteem, morale and team-working. 10 out of 24
soldiers have expressed an interest to pursue archaeology further; eight soldiers
disclosed mental health issues for the first time, four of whom required mental
health referral. CONCLUSIONS: GAPD can help early-returned soldiers in reducing
symptoms of anxiety, depression, isolation and psychological traumatic symptoms.
It also helps to increase perception of their ability to work and socialise as a
team and help them to an early return to work. It can provide soldiers with the
opportunity to approach their supervisors in an informal manner and help in early
detection of mental health problems.
PMID- 24351318
TI - Structural, vibrational, elastic and topological properties of PaN under
pressure.
AB - The electronic, structural, vibrational and elastic properties of PaN have been
studied at both ambient and high pressures, using first principles methods with
several commonly used parameterizations of the exchange-correlation energy. The
generalized gradient approximation (GGA) reproduces the ground state properties
satisfactorily. The high pressure behavior of the acoustic phonon branch along
the [1, 0, 0] and [1, 1, 0] directions and the C44 elastic constant are
anomalous, which signals a structural transition. With GGA exchange-correlation,
a topological transition in the charge density occurs near the structural
transition, which may be regarded as a quantum phase transition, where the order
parameter obeys a mean field scaling law. However, here it is found that the
topological transition is absent when other exchange-correlation functionals are
invoked (local density approximation (LDA) and hybrid functional). This
constitutes an example of GGA and LDA leading to qualitatively different
predictions, and therefore it is of great interest to examine experimentally
whether this topological transition occurs.
PMID- 24351319
TI - Self-harm in prisons in England and Wales: an epidemiological study of
prevalence, risk factors, clustering, and subsequent suicide.
AB - BACKGROUND: Self-harm and suicide are common in prisoners, yet robust information
on the full extent and characteristics of people at risk of self-harm is scant.
Furthermore, understanding how frequently self-harm is followed by suicide, and
in which prisoners this progression is most likely to happen, is important. We
did a case-control study of all prisoners in England and Wales to ascertain the
prevalence of self-harm in this population, associated risk factors, clustering
effects, and risk of subsequent suicide after self-harm. METHODS: Records of self
harm incidents in all prisons in England and Wales were gathered routinely
between January, 2004, and December, 2009. We did a case-control comparison of
prisoners who self-harmed and those who did not between January, 2006, and
December, 2009. We also used a Bayesian approach to look at clustering of people
who self-harmed. Prisoners who self-harmed and subsequently died by suicide in
prison were compared with other inmates who self-harmed. FINDINGS: 139,195 self
harm incidents were recorded in 26,510 individual prisoners between 2004 and
2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year.
Self-harm rates were more than ten times higher in female prisoners than in male
inmates. Repetition of self-harm was common, particularly in women and teenage
girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both
sexes, self-harm was associated with younger age, white ethnic origin, prison
type, and a life sentence or being unsentenced; in female inmates, committing a
violent offence against an individual was also a factor. Substantial evidence was
noted of clustering in time and location of prisoners who self-harmed (adjusted
intra-class correlation 0.15, 95% CI 0.11-0.18). 109 subsequent suicides in
prison were reported in individuals who self-harmed; the risk was higher in those
who self-harmed than in the general prison population, and more than half the
deaths occurred within a month of self-harm. Risk factors for suicide after self
harm in male prisoners were older age and a previous self-harm incident of high
or moderate lethality; in female inmates, a history of more than five self-harm
incidents within a year was associated with subsequent suicide. INTERPRETATION:
The burden of self-harm in prisoners is substantial, particularly in women. Self
harm in prison is associated with subsequent suicide in this setting. Prevention
and treatment of self-harm in prisoners is an essential component of suicide
prevention in prisons. FUNDING: Wellcome Trust, National Institute for Health
Research, National Offender Management Service, and Department of Health.
PMID- 24351320
TI - Cancer survival: global surveillance will stimulate health policy and improve
equity.
AB - Millions of people will continue to be diagnosed with cancer every year for the
foreseeable future. These patients all need access to optimum health care.
Population-based cancer survival is a key measure of the overall effectiveness of
health systems in management of cancer. Survival varies very widely around the
world. Global surveillance of cancer survival is needed, because unless these
avoidable inequalities are measured, and reported on regularly, nothing will be
done explicitly to reduce them.
PMID- 24351321
TI - Rethinking the war on cancer.
AB - Some 40 years ago a metaphor was posed that cancer was such an insidious
adversary that a declaration of war on the disease was justified. Although this
statement was a useful inspiration for enlistment of resources, despite
extraordinary progress in our understanding of disease pathogenesis, in most
cases and for most forms of cancer this war has not been won. A second metaphor
was about magic bullets--targeted therapies based on knowledge of mechanisms that
were envisaged to strike with devastating consequences for the disease. The
reality, however, is that targeted therapies are generally not curative or even
enduringly effective, because of the adaptive and evasive resistance strategies
developed by cancers under attack. In this Series paper, I suggest that, much
like in modern warfare, the war on cancer needs to have a battlespace vision.
PMID- 24351322
TI - Global cancer patterns: causes and prevention.
AB - Cancer is a global and growing, but not uniform, problem. An increasing
proportion of the burden is falling on low-income and middle-income countries
because of not only demographic change but also a transition in risk factors,
whereby the consequences of the globalisation of economies and behaviours are
adding to an existing burden of cancers of infectious origin. We argue that
primary prevention is a particularly effective way to fight cancer, with between
a third and a half of cancers being preventable on the basis of present knowledge
of risk factors. Primary prevention has several advantages: the effectiveness
could have benefits for people other than those directly targeted, avoidance of
exposure to carcinogenic agents is likely to prevent other non-communicable
diseases, and the cause could be removed or reduced in the long term--eg, through
regulatory measures against occupational or environmental exposures (ie, the
preventive effort does not need to be renewed with every generation, which is
especially important when resources are in short supply). Primary prevention must
therefore be prioritised as an integral part of global cancer control.
PMID- 24351323
TI - Preventing self-harm and suicide in prisoners: job half done.
PMID- 24351324
TI - The glycaemic index of fermented and non-fermented legume-based snack food.
AB - A study was conducted to estimate the glycaemic index (GI) of four isocaloric and
equicarbohydrate variations of the snack food 'cheela' (a savoury pancake) made
from powdered whole legumes Phaseolus aureus (green gram) and Cicer arierinum
(sengai gram) and their respective fermented batters. Fifteen healthy, normal
weight females aged 18-23 years comprised the sample. Glucose was used as a
reference food. The test meals were given within 4 weeks of reference food
administration, with at least 2 days interval between the test meals. The meals
and reference food were served at a fixed time in the morning, after a 12-h
overnight fast. Blood glucose was estimated at 0, 30, 60 and 120 min after eating
using an Ames glucometer II. The GI for the test meals ranged from 36% to 45%.
The green gram cheela (unfermented) had the lowest Gl (36 +/- 0.6%), peak blood
sugar value (111 .6 +/- 1.5 mg%) and AUC (2319 +/- 72) as compared to the other
three products. There was no significant difference between the fermented and the
corresponding unfermented preparations.
PMID- 24351325
TI - The prevalence of obesity and other coronary risk factors in a suburban Sri
Lankan community.
AB - Increasing numbers of developing nations experience a rising incidence of non
communicable diseases in parallel with economic development. Thus, developing
countries such as Sri Lanka face the double burden of both communicable and non
communicable diseases. We therefore conducted a study to assess the prevalence of
obesity, diabetes mellitus, impaired glucose tolerance (IGT), dyslipidaemias,
hypertension, central (android) obesity, hypertension and smoking habits in a
random sample of 633 (312 male) subjects selected from an electoral list with a
target population of 2974 persons. The prevalence (age standardized to the world
population of Segi 95% CI) was IGT 5.27 (3.74-7.78), diabetes 5.02 (3.59-6.53),
hypertension 15.25 (11.67-18.8), hypercholesterolaemia 14.86 (11.09-18.61),
hypertriglyceridaemia 8.46 (6.27-10.64), low HDL cholesterol 11.18 (8.35-13.99),
obesity 9.89 (7.24-12.52) and android obesity 16.35 (12.47-20.24). We conclude
that the high prevalence of coronary risk factors is an indication for initiating
programmes for primary prevention of obesity, diabetes and coronary heart disease
in Sri Lanka.
PMID- 24351326
TI - Immunomodulation of malnourished mice bearing Dalton's lymphoma.
AB - The immunomodulatory effect of a mouse bone-barrow-derived cytokine (BIM), (mol
wt<10 kd), was studied in mice bearing Dalton' s lymphoma. It was observed that
this factor increased the life-span of mice malnourished with respect to vitamin
B-complex and ascorbic acid and infected with Daltons' lymphoma, by 40+/-4 days
when compared to malnourished lymphoma controls while in animals maintained on
balanced diet (BDF) the increase in life-span was just over 11+/-2 days. In
cultured bone marrow cells at different time intervals after introduction of
lymphoma cells it was shown that introduction of lymphoma cells increased the
secretion of BIM. While the lymphoma developed the secretion of BIM diminished
much earlier in malnourished than in BDF mice. This observation further
strengthens our previous findings that the BIM acted as an immunomodulator much
more effectively in malnourished animals than in animals fed a balanced diet,
where a feed-back inhibitory effect might be present.
PMID- 24351327
TI - Determinants of serum levels of retinol, beta-carotene and alpha-tocopherol in
men and women born in Australia, Greece and Italy.
AB - Serum retinol, beta-carotene and alpha-tocopherol levels were measured in a
volunteer sample of 764 Australian-, Greek- and Italian-born adult residents of
Melbourne, Australia. There was no difference among the ethnic groups in mean
levels of serum retinol or alpha-tocopherol. Mean beta-carotene levels were
between 11 and 22% higher for Australian-born subjects. Serum beta-carotene was
higher in females, retinol was higher in males. The serum levels of retinol, beta
carotene and alpha-tocopherol were significantly positively associated with serum
cholesterol. Serum triglyceride was positively associated with serum retinol and
alpha-tocopherol but negatively associated with serum -beta-carotene. A positive
association with retinol and an inverse association with beta-carotene was found
for alcohol consumption. Serum alpha-tocopherol was positively associated with
dietary vitamin E. Serum beta-carotene was correlated with carotene intake among
subjects who had never smoked. Serum retinol increased with age in women only.
These data provide a degree of cross-cultural robustness to previous findings in
regard to the determinants of serum retinol, beta-carotene and alpha-tocopherol
in healthy men and women.
PMID- 24351328
TI - Anthropometric and clinical nutrition status of workers in some Indian factories.
AB - Anthropometric and clinical nutritional status of 195 male factory workers was
assessed in Nainital, North India. Relationships between anthropometry and
clinical scores and between nutritional status and either education or income
were evaluated. Mean +/- standard deviation values were: height 161.3 +/- 6.0 cm,
weight 52.7+/- 7.6 kg, BMI 20.2 +/- 2.4 and MUAC 24.0 +/- 2.3 cm. For BMI, 57% of
the subjects were below 20, a value below which FAO predicts that there will be
increased risk of work performance. Values corresponding to chronic energy
undernutrition (below 18.5 BMI) were found in about 20% of workers. Clinical
signs of nutritional deficiencies were found to be 10.76% for vitamin B complex,
2.05% for ascorbic acid and 2.05% for iron. Clinical scores and anthropometric
values were negatively correlated with each other, indicating that clinical signs
of nutritional deficiencies increased with decreasing anthropometric values.
Education and per capita income appeared to have a positive influence on
nutritional status.
PMID- 24351329
TI - Possible anti-tumour promoting properties of traditional Thai food items and some
of their active constituents.
AB - From a viewpoint of cancer chemoprevention, possible anti-tumour promoting
properties of daily food items and some of their active constituents have been
investigated by a convenient in-vitro assay, the Epstein-Barr virus (EBV)
activation test. In a screening test for the inhibitory activity toward EBV
activation by 40 methanol extracts from Thai edible plants used for flavours,
condiments or folk medicines, more than three-quarters of the total were found to
possess inhibitory activities. Significantly, the ratio of activity-exhibiting
plants was about three times higher than that of Japanese common vegetables and
fruits previously studied. The two plant families of Zingiberaceae and Rutaceae,
in particular, were suggested to be promising sources for highly effective anti
tumour promoters. Hitherto, geranial (Cymbopogon citratus, Gramineae), cardamonin
(Boesenbergia pandurata, Zingiberaceae). curcumin (Zingiber cassumunar,
Zingiberaceae) and 1-acetoxychavicol acetate (Languas galanga, Zingiberaceae)
have been idenflfied as the acfive constituents of strongly active plants in the
tumour promoter-induced EBV activation test. They showed more potent inhibitory
activities than the representative anti-tumour promoters such as beta-carotene or
quercetin. The high potential of the traditional food items of Thailand in the
search for potent anti-tumour promoters is described in this article.
PMID- 24351330
TI - Evaluation of a diabetes knowledge and behaviour (DKB) questionnaire.
AB - The primary prevention of type 2 (non-insulin-dependent) diabetes is now
considered possible through adopting lifestyle changes. Population strategies for
preventing diabetes are now being developed. The South Auckland Diabetes Project
has developed a questionnaire to assess the impact of a diabetes awareness,
exercise/healthy eating programme in the local communities. The questionnaire was
evaluated among local adult Europeans (n=127), Maori (n=103) and Pacific Islands
people (n =167). The questionnaire is interviewer-directed and takes
approximately 30 min to administer. Diabetes knowledge was assessed using four
open questions and 31 closed true/false questions which had good reliability
(Cronbach's a range: 0.59-0.90), reproducibility (Pearson's r range: 0.39-0.74)
and external validity (r range: 0.28-0.56) among all ethnic groups. Median scores
increased by 7-13% on re-testing. The open and closed question scores were 7-13%
and l0-26% higher respectively among those with diabetes or a family history of
diabetes (n = 78). Important dietary habits were assessed using four tools: (1) a
seven-item food preparation/fat content 'fat index'; (2) a four-item high
fat/high-refined-carbohydrate score had good reliability (Cronbach's alpha 0.51
0.74), reproducibility (r = 0.37-0.70) and external validity when compared with a
dietetic assessment (total fat r = 0.44-0.90); (3) a 12-item food frequency
questionnaire based on standard portion sizes also shared good reproducibility
(Pearson's r = 0.45-0.52) and correlated well with the dietetic assessment of
total calories (r = 0.48 0.64) and of calories due to fat (r = 0.41-0.65), and
(4) a simple question related to the frequency of fruit consumption correlated
negatively with the fat index in Europeans (r = 0.25, P<0.05) and Maori (r =
0.33, P<0.01). While the questionnaire does not give a quantitative assessment of
nutritional habits, it does offer a speedy tool for evaluating population-based
lifestyle and diabetes awareness interventions directed at the prevention and
control of type 2 (non-insulin-dependent) diabetes.
PMID- 24351331
TI - Responses of blood glucose and C-peptide to five Chinese starchy foods.
AB - Forty-nine patients with non-insulin-dependent diabetes mellitus (NIDDM) were
randomly divided into four groups (10-18 patients per group) to compare the
responses of blood glucose and C-peptide to some Chinese starchy foods. Ten
healthy subjects were used as controls. After an overnight fast, the blood
samples were drawn at fasting and 30, 60, 120, 180 minutes postprandially to
measure plasma glucose and serum C-peptide levels. Bun, which was made from
refined wheat flour and similar to white bread, was used in the assessment as the
reference food. Other test foods included rice, lotus seed, seed of gordon
euryale, and rhizome of common yam. There was only one kind of food in each test
meal, and each serving contained 50 g of carbohydrate. With both glycaemic index
(GI) and C-peptide index (CI) of bun set as 100 in this study, the GI and CI
respectively were: rice 89 and 91; lotus seed 62 and 72; seed of gordon euryale
102 and 102; rhizome of common yam 103 and 95. The GI and CI of lotus seed were
significantly lower than those of other test foods. It appears that lotus seed
may have a beneficial effect in NIDDM patients, and may be one of the more
appropriate foods for diabetic patients.
PMID- 24351332
TI - Efficiency of the iron supplementation programme for pregnant women in Jeneponto,
Sulawesi, Indonesia.
AB - An official iron supplementation programme for pregnant women in Jeneponto, South
Sulawesi, Indonesia was assessed for efficiency. Data were collected in a cross
sectional study of 107 women in the second or third trimester of pregnancy from
18 villages. 47.7% of the women were anaemic, although 63.6% stated they had
received prenatal care. Of the 68 women who had received prenatal care. 49 had
obtained iron tablets. However, 32.7% of the 49 women who received iron admitted
that they had not taken all of the tablets. Mean Hb levels of women in the second
trimester who had received tablets was 9 g/l higher (P=0.049) than that of women
who had not received tablets. To improve the efficiency of the iron
supplementation programme there must be an improvement in the coverage of pre
natal care, in the completeness of iron tablet distribution, and in efforts to
assure that the pregnant women actually take the tablets given to them.
PMID- 24351333
TI - Thiamine deficiency is associated with ethnicity in a subtropical area of China.
AB - Clinical signs which probably indicate thiamine (vitamin B1) deficiency have been
evident in the Meng Ding District of Yunnan province, China for decades. In 1990,
5979 people were surveyed using cluster sampling to investigate the association
of signs of thiamine deficiency with potential causative factors. Data on past
and present symptoms of thiamine deficiency were collected from individual
subjects, hospital records and health care personnel. Information on staple food
intake over the previous three months was collected from both individual subjects
and from commune administrations. Signs of thiamine deficiency occurred most
often in the Dai ethnic group. 5.1% of Dai males and 6.6% of Dai females had met
criteria for thiamine deficiency at some time over the previous 7 years. In other
ethnic groups, signs of thiamine deficiency occurred in only 0. 1% of males and
0.2% of females over the same time period. The incidence of signs of thiamine
deficiency did not vary with time during the 7 years prior to the survey, however
the condition appeared to be more severe (resulting in more cases of
hospitalization) in 1983-1985. Signs of thiamine deficiency showed a seasonal
distribution with the highest rates occurring in the hot, dry season. Signs of
thiamine deficiency were common among Dai women after childbirth. The findings
indicate that thiamine deficiency is strongly associated with ethnicity in this
population. It is likely that thiamine undernutrition is associated with dietary
intake and practices which differ by ethnic group. Public health measures to
minimize thiamine undernutrition in the Dai group include education and
supplementation.
PMID- 24351334
TI - Psychological distress in patients with a left ventricular assist device and
their partners: an exploratory study.
AB - BACKGROUND: Left ventricular assist device (LVAD) therapy is increasingly used in
patients with advanced heart failure, and may have a significant psychological
impact on both patients and their partners. Hence, we examined the distress
levels of LVAD patients and their partners. METHODS: Anxiety, depression and post
traumatic stress disorder (PTSD) were assessed at 3-4 weeks after implantation,
and at 3 and 6 months follow-up in 33 LVAD patients (73% men; mean age=54+/-10
years) and 33 partners (27% men; mean age=54+/-11 years). RESULTS: The prevalence
of anxiety in LVAD partners was significantly higher compared to LVAD patients at
baseline (48% vs. 23%, p=0.03) and 3 months follow-up (44% vs. 15%, p=0.02), but
not at 6 months follow-up (p=0.43). No differences were found for depression and
PTSD (ps>0.05). Scores between the LVAD patients and partners showed only a
significant correlation at baseline between the anxiety, depression and PTSD
score of the patient and the depression score of the partner (r anx=0.40, p=0.04;
rdep=.40, p=0.04; r PSTD=0.46, p=0.05). Multivariable analyses showed no
significant association between the role (patient vs. partner) and anxiety,
depression and PTSD over time after correction for age, gender and clinical
covariates. However, after correction for Type D personality and the use of
psychotropic medication the LVAD partners showed significantly higher anxiety
(F=6.95, p=0.01) and depression (F=3.94, p=0.04) scores over time compared to
LVAD patients. CONCLUSION: LVAD partners had significantly higher levels of
anxiety than LVAD patients. Emotional distress of LVAD partners should gain more
attention, as partners are an essential source of support for LVAD patients.
PMID- 24351335
TI - Sex-related differences and age of peak performance in breaststroke versus
freestyle swimming.
AB - BACKGROUND: Sex-related differences in performance and in age of peak performance
have been reported for freestyle swimming. However, little is known about the sex
related differences in other swimming styles. The aim of the present study was to
compare performance and age of peak performance for elite men and women swimmers
in breaststroke versus freestyle. METHODS: Race results were analyzed for
swimmers at national ranked in the Swiss high score list (during 2006 through
2010) and for international swimmers who qualified for the finals of the FINA
World Swimming Championships (during 2003 through 2011). RESULTS: The sex-related
difference in swimming speed was significantly greater for freestyle than for
breaststroke over 50 m, 100 m, and 200 m race distances for Swiss swimmers, but
not for FINA finalists. The sex-related difference for both freestyle and
breaststroke swimming speeds decreased significantly with increasing swimming
distance for both groups. Race distance did not affect the age of peak
performance by women in breaststroke, but age of peak performance was four years
older for FINA women than for Swiss women. Men achieved peak swimming performance
in breaststroke at younger ages for longer race distances, and the age of peak
swimming performance was six years older for FINA men than for Swiss men. In
freestyle swimming, race distance did not affect the age of peak swimming
performance for Swiss women, but the age of peak swimming performance decreased
with increasing race distance for Swiss men and for both sexes at the FINA World
Championships. CONCLUSIONS: Results of the present study indicate that (i) sex
related differences in swimming speed were greater for freestyle than for
breaststroke for swimmers at national level, but not for swimmers at
international level, and (ii) both female and male swimmers achieved peak
swimming speeds at younger ages in breaststroke than in freestyle. Further
studies are required to better understand differences between trends at national
and international levels.
PMID- 24351337
TI - Rhabdomyolysis and oliguric renal failure after use of TASER(r): is it really
safe?
PMID- 24351336
TI - Increase in antibody-dependent cellular cytotoxicity (ADCC) in a patient with
advanced colorectal carcinoma carrying a KRAS mutation under lenalidomide
therapy.
AB - The failure of EGFR inhibitors in colorectal tumors with KRAS mutations requires
the development of alternative treatment strategies for this patient subgroup.
Among the hallmarks of cancer the disturbed immunosurveillance and cancer immune
evasion have become emerging targets for cancer therapy. Due to their pleiotropic
functions immunomodulatory drugs (IMiDs) are interesting agents for combination
therapies in solid tumors. However, their possible contribution and a way of
monitoring their biological effects have yet to be revealed. In a heavily
pretreated patient with advanced colorectal cancer carrying mutations in APC and
KRAS genes, we show an early metabolic response and enhanced NK cell activity to
monotherapy with lenalidomide. After subsequent lenalidomide/cetuximab
combination treatment, the patient had progressive disease. At the same time a
reduced performance status, complicated by febrile neutropenia, occurred, as well
as a slight increase in metabolic activity. Concordantly NK cell activity dropped
back to baseline. Thus, laboratory measurements and metabolic response assessment
correlated with clinical conditions. This case report describes the feasibility
and potential of a functional assessment of patient derived immune competent
cells in combination with functional imaging for the detection of a biological
response.
PMID- 24351338
TI - A randomized clinical trial of synbiotic treatment before colorectal cancer
surgery.
PMID- 24351339
TI - Locally advanced hepatocellular carcinoma (Stage IVA): a role for hepatectomy?
PMID- 24351340
TI - Red light cameras reduce right-angle and rear-end crashes.
PMID- 24351341
TI - Nonresectional surgical approach to toxic megacolon with abdominal compartment
syndrome.
PMID- 24351342
TI - Primary thyroid paraganglioma: a rare entity affecting middle-aged women.
PMID- 24351343
TI - Eosinophilic jejunitis: is there a place for diagnostic laparoscopy?
PMID- 24351344
TI - Ultrasound-guided intraoperative transduodenal pancreatic head biopsy: a safe and
effective procedure to exclude malignancy in obstructive jaundice patients:
technical note.
PMID- 24351345
TI - Intraoperative endoscopic evaluation of the gastrojejunal anastomosis during
laparoscopic Roux-en-Y gastric bypass.
PMID- 24351346
TI - Some observations on the interdigitation of advances in medical science and
mathematics.
AB - The immense advancement of our understanding of disease processes has not been a
uniform progression related to the passage of time. Advances have been made in
"lurches" and "catches" since the advent of the written word. There has been a
remarkable interdependency between such advances in medicine and advances in
mathematics that has proved beneficial to both. This work explores some of these
critical relationships and documents how the individuals involved contributed to
advances in each.
PMID- 24351347
TI - What do patients think of medical students during their hospitalization? One
institution's experience.
AB - Multiple studies have shown patients have a positive attitude toward medical
students in outpatient facilities, but it is unknown whether these results can be
extrapolated to inpatients. The purpose of this study is to describe the
patients' attitude toward medical students in the inpatient facility and factors
that may affect it. A 43-item questionnaire was provided to patients of the
general surgery department; it gathered demographics, clinical condition, and
patients' opinions regarding the medical students' involvement in their care.
Eighty-four patients completed the questionnaire. Forty-three per cent were males
and the average age was 56 years old (range, 26 to 86 years). Sixty-one patients
(72.6%) felt that having medical students enhanced the care provided. Patients'
attitudes toward students were as follows: seven patients (8.3%) refused medical
students, 40 (47.6%) accepted a limited involvement, and 37 (44%) offered no
objections. Patients who refused medical students or preferred a limited
involvement were more likely to 1) consider their health as good or excellent; 2)
feel that the rounds were too early; and 3) feel that the residents did not spend
enough time with them. More patients prefer that medical students have a limited
involvement, especially when referring to minor procedures (e.g., nasogastric
tube, intravenous line). Better more thorough communication with patients
positively affects their attitudes toward students. More studies are required to
confirm these results and to analyze other factors that may improve the patients'
attitudes toward medical students.
PMID- 24351348
TI - Papillary lesions on core breast biopsy: excisional biopsy for all patients?
AB - Excisional biopsy has been recommended for papillary lesions diagnosed on core
needle biopsy (CNB) because a significant proportion of cases are upstaged to in
situ/invasive cancer after surgical excision. The study goals were to identify
patients at lowest risk of upstaging in whom excisional biopsy may potentially be
avoided. We retrospectively evaluated 46 patients with a papillary lesion on CNB.
Six patients were upstaged overall (13%), to intraductal papillary carcinoma
(7%), invasive papillary carcinoma (4%), and mixed invasive ductal/lobular
carcinoma (2%). The upstaging rate for patients with atypia on CNB was higher
than for patients without atypia (33 vs 3%, P = 0.011). No patient younger than
65 years was upstaged to in situ or invasive carcinoma, and the mean lesion size
was also higher among patients who were upstaged (P > 0.05). Patients younger
than 65 years with small papillary lesions lacking atypia on CNB may therefore
represent a low-risk group that may be offered close clinical and radiologic
follow-up.
PMID- 24351349
TI - One-step laparoscopic and endoscopic treatment of gallbladder and common bile
duct stones: our experience of the last 9 years in a retrospective study.
AB - The optimal timing and best method for removal of common bile duct stones (CBDS)
associated with gallbladder stones (GBS) is still controversial. The aim of this
study is to investigate the outcomes of a single-step procedure combining
laparoscopic cholecystectomy (LC), intraoperative cholangiography (IOC), and
endoscopic retrograde cholangiopancreatography (ERCP). Between January 2003 and
January 2012, 1972 patients underwent cholecystectomy at our hospital. Of those,
162 patients (8.2%; male/female 72/90) presented with GBS and suspected CBDS. We
treated 54 cases (Group 1) with ERCP and LC within 48 to 72 hours. In 108
patients (Group 2) we performed LC with IOC and, if positive, was associated with
IO-ERCP and sphincterotomy. In Group 1, a preoperative ERCP and LC were completed
in 50 patients (30%). In four cases (2%), an ERCP and endobiliary stents were
performed without cholecystectomy and then patients were discharged because of
the severity of clinical conditions and advanced American Society of
Anesthesiologists score (III to IV). Two months later a preoperative ERCP and
removal of biliary stents were performed followed by LC 48 to 72 hours later. In
Group 2, the IOC was performed in all cases and CBDS were extracted in 94
patients (87%). In two cases, the laparoscopic choledochotomy was necessary to
remove large stones. In another two cases, an open choledochotomy was performed
to remove safely the stones with T-tube drainage. In three cases, conversion was
necessary to safely complete the procedure. The mean operative time was 95
minutes (range, 45 to 150 minutes) in Group 1 and 130 minutes (range, 50 to 300
minutes) in Group 2. The mean hospital stay was 6.5 days (range, 4 to 21 days) in
Group 1 and 4.7 days (range, 3 to 14 days) in Group 2. Five cases (two in Group 2
and three in Group 1) presented with CBDS at 12 to 18 months after surgery. They
were treated successfully with a second ERCP. There was no perioperative
mortality. Our experience suggests that when clinically and technically feasible,
a single-stage approach combining LC, IOC, and ERCP to the patients diagnosed
with chole-choledocholithiasis is indicated. The IO-ERCP with CBDS extraction is
a safe and effective method with low risk of postoperative pancreatitis. One-step
treatment is more comfortable for the patient and also reduces the mean hospital
stay.
PMID- 24351350
TI - The impact of age on mortality in patients in extremis undergoing urgent
intervention.
AB - Trauma patients admitted without vital signs have little hope of survival even
with extreme interventions. We performed this study to determine the effect of
age on survival in patients in extremis undergoing urgent thoracotomy. The
National Trauma Database was searched for patients presenting without a systolic
blood pressure (0), a Glasgow Coma Scale score less than 8, and underwent an
urgent thoracotomy. Mortality was determined for pediatric (younger than 16
years) and older patients (older than 60 years) and compared. Of 708 patients, 32
(4.5%) were pediatric and 57 (8.1%) were elderly. Pediatric mortality was 93.8
per cent (30) versus 95.6 per cent (646) for patients older than 16 years (P =
0.981). Mortality in the older patients was 94.7 per cent (54) versus 95.5 per
cent (622) in patients younger than 60 years (P = 0.778). Race and blunt injury
were independently associated with death. However, neither pediatric (P = 0.418)
nor older status (P = 0.184) was predictive. Age does not significantly impact
mortality in patients in extremis who undergo urgent thoracotomy. Age should not
be a contributing factor in determining who should undergo more extreme maneuvers
if they present as a reasonable candidate using other criteria.
PMID- 24351351
TI - Contemporary experience with cholecystectomy: establishing 'benchmarks' two
decades after the introduction of laparoscopic cholecystectomy.
AB - With quality and public reporting of increasing importance, benchmarks are
anticipated to grow in relevance. We studied cholecystectomy in a practice in an
urban tertiary care hospital. A total of 1083 cholecystectomies were performed in
2008 and 2009. Laparoscopic cholecystectomy was performed in 97.8 per cent of
patients with a 2.2 per cent conversion rate. A planned open procedure was
performed in only 2.2 per cent of patients. Approximately half of procedures were
urgent and performed during an acute hospitalization. Most patients (74%) were
female and most patients were overweight or obese (64.8%). Ages into the tenth
decade of life were represented. Comorbidities included hypertension, 28.7 per
cent; coronary disease, 15.6 per cent; diabetes mellitus, 13.4 per cent;
gastroesophageal reflux disease, 10.7 per cent; and asthma, 5.5 per cent. Of
female patients, 98 (12.2%) were postpartum and five (0.6%) were pregnant. Of 137
patients without gallstones, 59.1 per cent had biliary dyskinesia and 27 per cent
had acalculous cholecystitis. Preoperative magnetic resonance
cholangiopancreatography and endoscopic retrograde cholangiopancreatography
(ERCP) were performed in most patients with suspected choledocholithiasis.
Intraoperative cholangiograms were performed in 6.9 per cent of patients, 3.3 per
cent for abnormal liver function studies. Postoperative ERCP was used in most
patients with positive intraoperative cholangiograms. All-cause mortality was 0.8
per cent and attributable mortality was 0.2 per cent. Complications occurred in
7.5 per cent of patients, including retained common bile duct stones in 1.1 per
cent, bile duct leak in 0.3 per cent, and common bile duct injury in 0.1 per
cent.
PMID- 24351352
TI - Does corticosteroid have any beneficial effect on voice change after
thyroidectomy?
AB - Voice alteration is one of the most common complications after thyroidectomy. It
has a serious effect on social communication and economic and psychosocial status
of patients. It has been hypothesized that inflammation and edema in the surgery
site has a major role in voice change after thyroidectomy. This randomized
clinical trial study was design to evaluate the effect of a single preoperative
dose of steroid on voice change after thyroidectomy. This is a prospective
randomized clinical trial with registration no. IRCT201106306925N. From all
definitive candidates for total thyroidectomy, eligible patients were selected
after exclusion of 12 criteria. Selected cases were randomly allocated to two
groups. One group received intravenous dexamethasone preoperatively. Other group
received placebo. Voice change was evaluated by Voice Impairment Score (VIS)
postoperatively. Sixty-four patients were entered in the study and divided into
two groups (dexamethasone and placebo). VIS was significantly different at the
first day after surgery between dexamethasone (five) and controls (13; P <
0.001). This difference was seen after 7 days but without statistically
significance (one vs three; P = 0.397). VIS score significantly decreased on the
seventh day related to the first day (P < 0.001) in both groups. There were no
significant dexamethasone complications in either group. Preoperative
dexamethasone may decrease voice change after thyroidectomy.
PMID- 24351353
TI - Comparison of the three surgical flap techniques in pilonidal sinus surgery.
AB - We aimed to study the efficacy of three surgical flap techniques in pilonidal
surgery. Pilonidal disease is characterized by chronic inflammation and infection
in the sacrococcygeal region. Complications and recurrence are common after
treatment and optimal treatment for the disease has not been established yet. We
enrolled a total of 401 patients in this study. Patients have been treated with
Karydakis (n = 113), modified Limberg (n = 179), or Limberg (n = 109) flap
techniques. Mean off-work period, time to walk without pain, time to sit on the
toilet, time to take the drainage catheter off, maceration rates, recurrence, and
hypoesthesia rates were significantly better in the modified Limberg group. In
conclusion, we showed the modified Limberg technique is superior than both
Limberg and Karydakis techniques.
PMID- 24351354
TI - Surgeons do not listen: evaluation of compliance with antimicrobial stewardship
program recommendations.
AB - The purpose of this study was to determine if there are differences in
interventions (int) required and compliance (comp) to recommendations (rec) by
medical and surgical services as determined by an antimicrobial stewardship
program (ASP). Concurrently collected ASP data from January 2008 through May 2011
were evaluated to determine number of int required and response to int. Results
for medical (med) and surgical (surg) services were compared. There were 2322
int, of which 1108 were for med and 1214 were for surg. Recs were as follows: 242
appropriate coverage (AC) med versus 212 AC surg and 866 selective pressure (SP)
med and 1002 SP surg. Comp with recs was higher for med: AC: 90.5 per cent (219
of 242) med versus 82.1 per cent (174 of 212) surg (P = 0.0086) and SP: 81.1 per
cent (702 of 866) med versus 69.5 per cent (696 of 1002) surg (P < 0.0001).
Overall surgical comp with ASP recs was better for AC than for SP. Moreover, less
than half (seven of 15) of the surgical subspecialties demonstrated a comp of 75
per cent or greater with SP recs with only one-fifth having a comp over 80 per
cent. Surgical services demonstrate poor compliance with ASP recommendations;
this is especially true for interventions targeting selective pressure. By
identifying services that are less compliant, programs can target their
educational efforts to improve outcomes.
PMID- 24351355
TI - Comparison of hand-assisted laparoscopic and open radical distal gastrectomy for
obese patients.
AB - To evaluate the feasibility and safety of hand-assisted laparoscopic surgery for
gastric cancer in obese patients, we compare the operative outcomes in obese
patients who underwent hand-assisted laparoscopic distal gastrectomy (HALDG) and
open distal gastrectomy (ODG). One hundred sixty-two obese patients with gastric
cancer operated on in our department from January 2009 to December 2011 were
divided into two groups: the open distal gastrectomy group (the ODG group) and
the hand-assisted laparoscopic distal gastrectomy group (the HALDG group).
Operative time, estimated blood loss, number of lymph node retrieval, wound
length, times of analgesic injection, time to the first flatus, and postoperative
hospital stay were compared between the two groups. Estimated blood loss, wound
length, times of analgesic injection, time to the first flatus, and postoperative
hospital stay were significantly less or shorter in the HALDG group than in the
ODG group. There were no significant differences in tumor size, retrieved lymph
nodes, American Joint Cancer Committee /Union Internationale Contre le Cancer
staging, and resection margins between the two groups. Obesity should not be seen
as a contraindication for HALDG. HALDG for obese patients is a safe, feasible,
and oncologically sound procedure and has advantages over ODG.
PMID- 24351356
TI - Self-expanding metallic stents in acute mechanical intestinal obstructions
resulting from colorectal malignancies.
AB - Endoscopic colonic stenting with self-expanding metallic stents is now widely
used to treat malignant large bowel obstruction, where temporary or permanent
decompression of the large bowel is desired. The medical records of patients who
underwent endoscopic colonic stenting for malignant large bowel obstruction
between May 2004 and May 2011 were reviewed. Success rate, morbidity, and
mortality rate along with patient characteristics were documented. Sixty-seven
patients were included. The procedure was used as a bridge to surgery in 38 and
as a palliative measure in 29. Success rate was 95.5 per cent. Perforation and
reobstruction occurred in three and three patients, respectively. All of the
patients who developed perforation or reobstruction underwent emergency surgery.
Endoscopic stenting offers a safe and effective treatment option in patients with
malignant large bowel obstruction with comparable outcomes.
PMID- 24351357
TI - Total thyroidectomy as primary definitive treatment for Graves' hyperthyroidism.
AB - The objective of this study was to compare the results of total thyroidectomy
(TT) for hyperthyroidism secondary to Graves' disease (GD) with TT for other
benign thyroid diseases to determine if TT should be considered more often as
first-line therapy for GD. Seven hundred eighty patients underwent TT for benign
disease: 203 for GD, 56 for other hyperthyroidisms, and 521 for other benign
diseases from March 1, 2003, to December 31, 2009. The perioperative results of
these three groups were compared for demographics, blood loss, operative time,
complications, and hospitalization. There were no significant differences among
the three groups except the patients with GD were more likely to be younger (42
vs 56 vs 57 years; P < 0.001), have more blood loss (154 vs 99 vs 110 mL; P =
0.05), and were more likely to develop permanent hypoparathyroidism (1.0 vs 1.8
vs 0%; P = 0.03) when compared with other causes of hyperthyroidism and other
benign thyroid diseases. Permanent recurrent laryngeal nerve injury did not occur
in the GD group (0 vs 0 vs 0.4% nerves at risk; P = 0.69) with transient
recurrent laryngeal nerve injury occurring in 1.7 versus 2.7 versus 3.1 per cent
nerves at risk (P = 0.35). The lack of a euthyroid state preoperatively had no
influence on surgical outcomes or complications. Eighty percent of the TTs for GD
were done as same-day outpatient procedures. TT offers a safe, low-risk, and
rapid cure for GD to justifiably be considered as a reasonable first-line therapy
in selected patients with Graves' hyperthyroidism.
PMID- 24351358
TI - Does alcohol intoxication protect patients from severe injury and reduce hospital
mortality? The association of alcohol consumption with the severity of injury and
survival in trauma patients.
AB - Alcohol-related motor vehicle collisions are a major cause of mortality in trauma
patients. This prospective observational study investigated the influence of
antecedent alcohol use on outcomes in trauma patients who survived to reach the
hospital. From 2005 to 2011, all patients who were older than 18 years and were
admitted as a result of motor vehicle crashes were included. Blood alcohol
concentration (BAC) was routinely measured for each patient on admission.
Patients were divided into four groups based on their BAC level, which included
nondrinking, BAC less than 100, BAC 100 to 200, and BAC 200 mg/dL or greater.
Patient demographics, physical status and injury severity on admission, length of
hospital stay, and outcome were compared between the groups. Odds ratios of
having a severe injury, prolonged hospital stay, and mortality were estimated.
Patients with a positive BAC had an increased risk of sustaining craniofacial and
thoracoabdominal injuries. Odds ratios of having severe injuries (Injury Severity
Score [ISS] 16 or greater) and a prolonged hospital stay were also increased.
However, for those patients whose ISS was 16 or greater and who also had a brain
injury, risk of fatality was significantly reduced if they were intoxicated (BAC
200 mg/dL or greater) before injury. Alcohol consumption does not protect
patients from sustaining severe injuries nor does it shorten the length of
hospital stay. However, there were potential survival benefits related to alcohol
consumption for patients with brain injuries but not for those without brain
injuries. Additional research is required to investigate the mechanism of this
association further.
PMID- 24351359
TI - Validation of the sentinel lymph node biopsy technique in head and neck cancers
of the oral cavity.
AB - The purpose of this study was to present our experience and validate the use of
sentinel lymph node (SLN) mapping in patients with head and neck cancers. A
retrospective review of a prospectively collected database of patients with a
diagnosis of squamous cell carcinomas of the head and neck from 2008 to 2011 was
done. The group consisted of a total of 20 patients. The first node(s)
highlighted with blue, or identified as radioactive by Tc99-sulfur radioactive
colloid, was (were) identified as the SLNs. In the first seven patients, formal
modified neck dissection was performed. In the remaining 13 patients, only a SLN
biopsy procedure was done. At least one SLN was identified in all 20 patients
(100%). Only one patient (5%) had positive nodes. In this case, the SLN was also
positive. In the remaining 19 cases, all lymph nodes were negative. After an
average of 24 months of follow-up, there have been three local recurrences (15%)
but no evidence of distant metastatic disease. SLN mapping in head and neck
cancers is a feasible technique with a high identification rate and a low false
negative rate. Although the detection rate of regional metastatic disease
compares favorably with published data as well as the disease-free and overall
survival, further studies are warranted before considering this technique to be
the "gold standard" in patients with oral squamous cell carcinoma and a negative
neck by clinical examination and imaging studies.
PMID- 24351360
TI - Use of polypropylene mesh in the management of a contaminated large ventral
hernia: a contraindication or a solution?
AB - Management of contaminated large ventral hernias is still a challenge as a result
of massive loss of muscular and fascial tissues in the abdominal wall,
traditional contraindication to use of a prosthesis, and complicated
perioperative management. This study aimed to provide a solution for this
challenging dilemma using monofilament polypropylene mesh (Marlex; Bard) in the
Sublay-Bridge fashion. Twenty-three consecutive patients with contaminated large
ventral hernias from 2009 to 2011 were identified. Preoperatively, source of
contamination at the surgical site was managed through oral antibiotics, wound
debridement, and dressing change; the hernia content was reduced into the
abdominal cavity gradually and an abdominal binder was applied. Marlex meshes in
the Sublay-Bridge fashion were used in these patients. Demographic and
perioperative data were collected. Fourteen males and nine females were included
with a mean age of 52.5 +/- 10.5 years and a mean body mass index of 25.2 +/- 6.1
kg/m(2). Twelve patients underwent ostomy takedown, which was the most common
indication. Mean hernia size was 120.5 +/- 18.5 cm(2) and a mean mesh size was
380.0 +/- 80.5 cm(2). The mean operative time was 125.5 +/- 35.5 minutes and the
hospital stay was 10.0 +/- 3.5 days. Twenty-three patients had a mean follow-up
period of 12.5 +/- 6.5 months. An iatrogenic bladder injury occurred because of
severe prevesical adhesion attributed to previous prosthesis repair. There was no
presentation of abdominal compartment syndrome. Four patients developed surgical
site infection and managed with conservative therapy without mesh removal. Three
patients had seromas and underwent aspiration guided by B-ultrasound. Three
patients reported chronic foreign body sensation. No recurrence was followed up.
Repair of contaminated large ventral hernia using a Marlex mesh in the Sublay
Bridge fashion is safe and efficient management. Perioperative management and
operative technology play important roles in dealing with this problem.
PMID- 24351361
TI - Scarless laparotomy in children: a transumbilical technique with umbilicoplasty.
PMID- 24351362
TI - Is routine splenic flexure mobilization always mandatory for left colectomy? A
comparative study of 80 patients with adenocarcinoma of the sigmoid colon.
PMID- 24351363
TI - Assessment of surgical residents' ability to predict appendicitis with computed
tomography.
PMID- 24351364
TI - Hand necrosis resulting from cannulation injury of the radial artery.
PMID- 24351365
TI - One horsepower versus multiple horsepower in pediatric trauma.
PMID- 24351366
TI - Deer-vehicle collisions are associated with worsened outcomes for motorcyclists
and direct collisions.
PMID- 24351367
TI - The transversus abdominis plane block after postbariatric abdominoplasty: reasons
for pitfalls.
PMID- 24351368
TI - Rectal diverticulum after stapled transanal procedures: surgery encouraged.
PMID- 24351369
TI - Hemolysis in pediatric patients receiving centrifugal-pump extracorporeal
membrane oxygenation: prevalence, risk factors, and outcomes.
AB - OBJECTIVES: To explore the prevalence and risk factors for hemolysis in children
receiving extracorporeal membrane oxygenation and examine the relationship
between hemolysis and adverse outcomes. DESIGN: Retrospective, single-center
study. SETTING: Tertiary PICU. PATIENTS: Two hundred seven children receiving
extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: Plasma-free hemoglobin was tested daily and hemolysis was diagnosed
based on peak plasma-free hemoglobin as mild (< 0.5 g/L), moderate (0.5-1.0 g/L),
or severe (> 1.0 g/L). Gender, age, weight, diagnosis, oxygenator type,
cannulation site, mean venous inlet pressure, mean pump speed, mean flow, and
visible clots in the extracorporeal membrane oxygenation circuit were entered
into the ordered logistic regression model to identify risk factors of hemolysis.
Complications and clinical outcomes were compared across four hemolysis groups.
Of the 207 patients, 69 patients (33.3%; 95% CI, 27.0-40.2%) did not have
hemolysis, 98 patients (47.3%; 95% CI, 40.4-54.4%) had mild hemolysis, 26
patients (12.5%; 95% CI, 8.4-17.9%) had moderate hemolysis, and 14 patients
(6.8%; 95% CI, 3.7-11.1%) had severe hemolysis with a median peak plasma-free
hemoglobin of 1.51 g/L (1.18-2.05 g/L). The independent risk factors for
hemolysis during extracorporeal membrane oxygenation were use of Quadrox D (odds
ratio, 7.25; 95% CI, 3.10-16.95; p < 0.001) or Lilliput (odds ratio, 37.32; 95%
CI, 8.95-155.56; p < 0.001) oxygenators, mean venous inlet pressure (odds ratio,
0.95; 95% CI, 0.91-0.98; p = 0.002), and mean pump speed (odds ratio, 2.89; 95%
CI, 1.36-6.14; p = 0.006). Patients with hemolysis were more likely to experience
a longer extracorporeal membrane oxygenation run and require more blood products.
After controlling for age, weight, pediatric index of mortality 2, and diagnosis,
patients with severe hemolysis were more likely to die in the ICU (odds ratio,
5.93; 95% CI, 1.64-21.43; p = 0.007) and in hospital (odds ratio, 6.34; 95% CI,
1.71-23.54; p = 0.006). CONCLUSIONS: Hemolysis during extracorporeal membrane
oxygenation with centrifugal pumps was common and associated with a number of
adverse outcomes. Risk factors for hemolysis included oxygenator types, mean
venous inlet pressure, and mean pump speed. Further studies are warranted
comparing pump types while controlling both physical and nonphysical confounders.
PMID- 24351370
TI - Outcomes and complications of intracranial pressure monitoring in acute liver
failure: a retrospective cohort study.
AB - OBJECTIVE: To determine if intracranial pressure monitor placement in patients
with acute liver failure is associated with significant clinical outcomes.
DESIGN: Retrospective multicenter cohort study. SETTING: Academic liver
transplant centers comprising the U.S. Acute Liver Failure Study Group. PATIENTS:
Adult critically ill patients with acute liver failure presenting with grade
III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004
and August 2011. INTERVENTION: Intracranial pressure monitored (n = 140) versus
nonmonitored controls (n = 489). MEASUREMENTS AND MAIN RESULTS: Intracranial
pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001)
and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87
intracranial pressure monitored patients with detailed information, 44 (51%) had
evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and
overall 21-day mortality was higher in patients with intracranial hypertension
(43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored
patients received more intracranial hypertension-directed therapies (mannitol,
56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for
each). Forty-one percent of intracranial pressure monitored patients received
liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was
similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where
data were available, hemorrhagic complications were rare in intracranial pressure
monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen
status and adjusting for confounders, intracranial pressure monitor placement did
not impact 21-day mortality in acetaminophen patients (p = 0.89). However,
intracranial pressure monitor was associated with increased 21-day mortality in
nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014). CONCLUSIONS: In
intracranial pressure monitored patients with acute liver failure, intracranial
hypertension is commonly observed. The use of intracranial pressure monitor in
acetaminophen acute liver failure did not confer a significant 21-day mortality
benefit, whereas in nonacetaminophen acute liver failure, it may be associated
with worse outcomes. Hemorrhagic complications from intracranial pressure monitor
placement were uncommon and cannot account for mortality trends. Although our
results cannot conclusively confirm or refute the utility of intracranial
pressure monitoring in patients with acute liver failure, patient selection and
ancillary assessments of cerebral blood flow likely have a significant role.
Prospective studies would be required to conclusively account for confounding by
illness severity and transplant.
PMID- 24351372
TI - Feasibility and economic impact of dedicated hospice inpatient units for
terminally ill ICU patients.
AB - OBJECTIVES: End-of-life care is frequently provided in the ICU because patients
receiving life-sustaining treatments are often unsuitable for transfer to home or
community hospices. In-hospital dedicated hospice inpatient units are a novel
option. This study was designed to 1) demonstrate the feasibility of ICU to
dedicated hospice inpatient unit transfer in critically ill terminal patients; 2)
describe the clinical characteristics of those transferred and compare them to
similar patients who were not transferred; and 3) assess the operational and
economic impact of dedicated hospice inpatient units. DESIGN: Retrospective chart
review. SETTING: ICUs and dedicated hospice inpatient units at two southeast
urban university hospitals. INTERVENTIONS: Charts of ICU and dedicated hospice
inpatient unit deaths over a 6-month period were reviewed. PATIENTS: Dedicated
hospice inpatient unit transfers were identified from hospice administrator
records. Missed opportunities were patients admitted to the hospital for more
than 48 hours who either adopted a comfort care course or had a planned
termination of life-sustaining therapy. Patients were excluded if they were
declared brain dead, were organ donors, required high-frequency ventilation, or
if there was insufficient information in the medical record to make a
determination. MEASUREMENTS AND MAIN RESULTS: We identified 167 transfers and 99
missed opportunities; 37% of appropriate patients were not transferred. Transfers
were older (66.9 vs 60.4 yr; p < 0.05), less likely to use mechanical ventilation
(71.9% vs 90.9%) and vasopressors (70.9% vs 95.0%; p < 0.05), and less likely to
receive a palliative care consult (70.4% vs 43.4%; p < 0.05) than missed
opportunities. Transfers saved 585 ICU bed days. CONCLUSIONS: Dedicated hospice
inpatient units are a feasible way to provide care for terminal ICU patients, but
barriers including lack of knowledge of the units and provider or family comfort
with leaving the ICU remain. Dedicated hospice inpatient units are potentially
significant sources of bed days and cost savings for hospitals and the healthcare
system overall.
PMID- 24351373
TI - Early mobilization of mechanically ventilated patients: a 1-day point-prevalence
study in Germany.
AB - OBJECTIVES: There is growing evidence to support early mobilization of adult
mechanically ventilated patients in ICUs. However, there is little knowledge
regarding early mobilization in routine ICU practice. Hence, the
interdisciplinary German ICU Network for Early Mobilization undertook a 1-day
point-prevalence survey across Germany. DESIGN: One-day point-prevalence study.
SETTING: One hundred sixteen ICUs in Germany in 2011. PATIENTS: All adult
mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: For a 24-hour period, data were abstracted on hospital and ICU
characteristics, the level of patient mobilization and associated barriers, and
complications occurring during mobilization. One hundred sixteen participating
ICUs provided data for 783 patients. Overall, 185 patients (24%) were mobilized
out of bed (i.e., sitting on the edge of the bed or higher level of
mobilization). Among patients with an endotracheal tube, tracheostomy, and
noninvasive ventilation, 8%, 39%, and 53% were mobilized out of bed, respectively
(p < 0.001 for difference between three groups). The most common perceived
barriers to mobilizing patients out of bed were cardiovascular instability (17%)
and deep sedation (15%). Mobilization out of bed versus remaining in bed was not
associated with a higher frequency of complications, with no falls or extubations
occurring in those mobilized out of bed. CONCLUSIONS: In this 1-day point
prevalence study conducted across Germany, only 24% of all mechanically
ventilated patients and only 8% of patients with an endotracheal tube were
mobilized out of bed as part of routine care. Addressing modifiable barriers for
mobilization, such as deep sedation, will be important to increase mobilization
in German ICUs.
PMID- 24351374
TI - The effects of different IV fat emulsions on clinical outcomes in critically ill
patients.
AB - OBJECTIVE: To examine the effects of different IV fat emulsions on clinical
outcomes in critically ill patients. DESIGN: Secondary analysis of data from a
prospective multicenter study. SETTING: An international sample of ICUs.
PATIENTS: Adult patients who were admitted to the ICU for more than 72 hours,
were mechanically ventilated within 48 hours, received exclusive parenteral
nutrition for more than or equal to 5 days, and did not change IV fat emulsion
type during the data collection period. INTERVENTIONS: Demographic and clinical
data were collected for up to 12 days, until death, or discharge from the ICU,
whichever came first. Clinical outcomes were recorded at 60 days following ICU
admission. MEASUREMENTS: Lipid-free, soybean, medium-chain triglyceride, olive,
and fish oils in parenteral nutrition were compared using an adjusted Cox
proportional hazard model to examine time to termination of mechanical
ventilation alive, time to ICU discharge alive, and time to hospital discharge
alive. MAIN RESULTS: A total of 451 patients were included in this study: 70
(15.5%) in the lipid-free group, 223 (49.5%) in the soybean oil group, 65 (14.4%)
in the medium-chain triglyceride group, 74 (16.4%) in the olive oil group, and 19
(4.9%) in the fish oil group. When compared with lipid-free parenteral nutrition,
patients who received fish oil had a faster time to ICU discharge alive (hazard
ratio, 1.84; 95% CI, 1.01-3.34; p = 0.05). When compared with soybean oil,
patients who received olive oil or fish oil had a shorter time to termination of
mechanical ventilation alive (hazard ratio, 1.43; 95% CI, 1.06-1.93; p = 0.02 and
hazard ratio, 1.67; 95% CI, 1.00-2.81; p = 0.05, respectively) and a shorter time
to ICU discharge alive (hazard ratio, 1.76; 95% CI, 1.30-2.39; p < 0.001 and
hazard ratio, 2.40; 95% CI, 1.43-4.03; p = 0.001, respectively). CONCLUSIONS: Use
of alternative IV fat emulsions in parenteral nutrition, particularly olive and
fish oil, was associated with improved clinical outcomes.
PMID- 24351371
TI - A multinational study of thromboprophylaxis practice in critically ill children.
AB - OBJECTIVES: Although critically ill children are at increased risk for developing
deep venous thrombosis, there are few pediatric studies establishing the
prevalence of thrombosis or the efficacy of thromboprophylaxis. We tested the
hypothesis that thromboprophylaxis is infrequently used in critically ill
children even for those in whom it is indicated. DESIGN: Prospective
multinational cross-sectional study over four study dates in 2012. SETTING: Fifty
nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the
United States. PATIENTS: All patients less than 18 years old in the PICU during
the study dates and times were included in the study, unless the patients were 1)
boarding in the unit waiting for a bed outside the PICU or 2) receiving
therapeutic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
Of 2,484 children in the study, 2,159 (86.9%) had greater than or equal to 1 risk
factor for thrombosis. Only 308 children (12.4%) were receiving pharmacologic
thromboprophylaxis (e.g., aspirin, low-molecular-weight heparin, or
unfractionated heparin). Of 430 children indicated to receive pharmacologic
thromboprophylaxis based on consensus recommendations, only 149 (34.7%) were
receiving it. Mechanical thromboprophylaxis was used in 156 of 655 children
(23.8%) 8 years old or older, the youngest age for that device. Using nonlinear
mixed effects model, presence of cyanotic congenital heart disease (odds ratio,
7.35; p < 0.001) and spinal cord injury (odds ratio, 8.85; p = 0.008) strongly
predicted the use of pharmacologic and mechanical thromboprophylaxis,
respectively. CONCLUSIONS: Thromboprophylaxis is infrequently used in critically
ill children. This is true even for children at high risk of thrombosis where
consensus guidelines recommend pharmacologic thromboprophylaxis.
PMID- 24351375
TI - A randomized, double-blind, placebo-controlled dose range study of
dexmedetomidine as adjunctive therapy for alcohol withdrawal.
AB - OBJECTIVES: To evaluate dexmedetomidine as adjunctive therapy to lorazepam for
severe alcohol withdrawal. DESIGN: Prospective, randomized, double-blind, placebo
controlled trial. SETTING: Single center; medical ICU. PATIENTS: Twenty-four
adult patients with a Clinical Institute Withdrawal Assessment score greater than
or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour
period. INTERVENTIONS: Patients received a symptom-triggered Clinical Institute
Withdrawal Assessment protocol with lorazepam and were randomized to
dexmedetomidine 1.2 MUg/kg/hr (high dose), 0.4 MUg/kg/hr (low dose), or placebo
as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms.
MEASUREMENT AND MAIN RESULTS: High-dose and low-dose groups were combined as a
single dexmedetomidine group for primary analysis with secondary analysis
exploring a dose-response relationship. The difference in 24-hour lorazepam
requirements after versus before study drug was greater in the dexmedetomidine
group compared with the placebo group (-56 mg vs -8 mg, p = 0.037). Median
differences were similar for high dose and low dose. The 7-day cumulative
lorazepam requirements were not statistically different between dexmedetomidine
and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker
sedation-agitation scale scores representing severe agitation (13% vs 25%) or
moderate agitation (27% vs 22%) within 24 hours of initiating study drug were
similar for dexmedetomidine and placebo groups, respectively. Bradycardia
occurred more frequently in the dexmedetomidine group versus placebo group (25%
vs 0%, p = not significant), with the majority of bradycardia occurring in the
high-dose group (37.5%). Study drug rate adjustments occurred more often in the
dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02).
Neither endotracheal intubation nor seizure occurred in any group while on study
drug. CONCLUSIONS: Adjunctive dexmedetomidine for severe alcohol withdrawal
maintains symptom control and reduces lorazepam exposure in the short term, but
not long term, when using a symptom-triggered protocol. Monitoring for
bradycardia is needed with dexmedetomidine but the occurrence may be lessened
with low dose. Further study is needed to evaluate the clinical impact of
dexmedetomidine.
PMID- 24351377
TI - Toward a community-centered public service system for universal health care in
India.
PMID- 24351376
TI - Risk factors for postoperative pneumonia after cardiac surgery and development of
a preoperative risk score*.
AB - OBJECTIVES: The aims of this study were, first, to identify risk factors for
microbiology-proven postoperative pneumonia after cardiac surgery and, second, to
develop and validate a preoperative scoring system for the risk of postoperative
pneumonia. DESIGN AND SETTING: A single-center cohort study. PATIENTS: All
consecutive patients undergoing cardiac surgery between January 2006 and July
2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis
of risk factors for postoperative pneumonia was performed on data from patients
operated between January 2006 and December 2008 (training set). External temporal
validation was performed on data from patients operated between January 2009 and
July 2011 (validation set). Preoperative variables identified in multivariate
analysis of the training set were then used to develop a preoperative scoring
system that was validated on the validation set. Postoperative pneumonia occurred
in 174 of the 5,582 patients (3.1%; 95% CI, 2.7-3.6). Multivariate analysis
identified four risk factors for postoperative pneumonia: age (odds ratio, 1.02;
95% CI, 1.01-1.03), chronic obstructive pulmonary disease (odds ratio, 2.97; 95%
CI, 1.8-4.71), preoperative left ventricular ejection fraction (odds ratio, 0.98;
95% CI, 0.96-0.99), and the interaction between RBC transfusion during surgery
and duration of cardiopulmonary bypass (odds ratio, 2.98; 95% CI, 1.96-4.54). A 6
point score including the three preoperative variables then defined two risk
groups corresponding to postoperative pneumonia rates of 1.8% (score < 3) and
6.5% (score >= 3). CONCLUSION: Assessing preoperative risk factors for
postoperative pneumonia with the proposed scoring system could help to implement
a preventive policy in high-risk patients with a risk of postoperative pneumonia
greater than 4% (i.e., patients with a score >= 3).
PMID- 24351378
TI - Medical technology in India: Tracing policy approaches.
AB - Medical devices and equipment have become an indispensable part of modern medical
practice. Yet these medical technologies receive scant attention in the Indian
context, both at the health policy level and as an area of study. There has been
little attempt to systematically address the issue of equipment based medical
technologies and how to regulate their use. There is paucity of primary data on
the kind of medical equipment and techniques being introduced, on their need and
relative usefulness, reliability, patterns of utilization, on their production,
procurement, distribution, costs, and accessibility. This article reviews some of
the policy issues relating to equipment based medical technology in India, in
light of the specific choices and policies made during and after the colonial
period in favour of modern medicine and a technology-based public health system,
attempts at self-sufficiency and the current international environment with
respect to the medical equipment and health-care industry.
PMID- 24351379
TI - Medical equipment industry in India: Production, procurement and utilization.
AB - This article presents information on the medical equipment industry in India-on
production, procurement and utilization related activities of key players in the
sector, in light of the current policies of liberalization and growth of a
"health-care industry" in India. Policy approaches to medical equipment have been
discussed elsewhere.
PMID- 24351380
TI - Challenges for regulating the private health services in India for achieving
universal health care.
AB - Commercial interests pose a serious challenge for universalizing health-care.
This is because "for-profit" health-care privileges individual responsibility and
choice over principles of social solidarity. This fundamentally opposing tendency
raises ethical dilemmas for designing a health service that is universal and
equitable. It is an inadequate to merely state the need for regulating the
private sector, the key questions relate to what must be done and how to do it.
This paper identifies the challenges to regulating the private health services in
India. It argues that regulation has been fragmented and largely driven by the
center. Given the diversity of the private sector and health being a state
subject, regulating this sector is fraught with the technical and socio-political
factors.
PMID- 24351381
TI - Aren't technological choices central to designing health systems?
AB - This paper argues that delivery of technology-based preventive, promotive and
curative care is one of the central tasks of any health-care system and therefore
it forms one of the central pivots for rational structuring/re-structuring of a
health-care system. The development of our public health system has,
historically, adopted health technologies (HT) uncritically and thereby not
explicitly developed institutional mechanisms to assess them for rational choice.
Determinants of HT policy choices and structuring of a service delivery system
based on that are discussed with examples of modern low cost HT, technologies of
codified health knowledge systems other than the modern and local health
traditions. Various forms of institutional structures for HT assessment and R and
D using a comprehensive primary health-care approach are suggested.
PMID- 24351382
TI - Developing a public health cadre in 21 st century India: addressing gaps in
technical, administrative and social dimensions of public health services.
AB - This paper presents a possible framework for designing a public health cadre in
the present context, with lessons from health services development of the last
six decades. Three major gaps that the public health cadre is meant to bridge
have been identified. These are capacities within the system to address the
technical requirements (epidemiological and health systems analysis);
administrative/managerial dimensions; and the social determinants of health.
Therefore, it argues that the cadre must not only have a techno-managerial
structure, but also create a specific sub-cadre for the social determinants of
health.
PMID- 24351383
TI - Universal health care in India: Panacea for whom?
AB - This paper examines the current notion of universal health care (UHC) in key
legal and policy documents and argues that the recommendations for UHC in these
entail further abdication of the State's responsibility in health care with the
emphasis shifting from public provisioning of services to merely ensuring
universal access to services. Acts of commission (recommendations for public
private partnership [PPPs], definition and provision of an essential health
package to vulnerable populations to ensure universal access to care) and
omission (silence maintained on tertiary care) will eventually strengthen the
private and corporate sector at the cost of the public health care services and
access to care for the marginalized. Thus, the current UHC strategy uses equity
as a tool for promoting the private sector in medical care rather than health for
all.
PMID- 24351384
TI - Contradictions of the health-care system in India and a strategy for health-care
for all.
AB - The contradiction between the socialized nature of the modern health-care system
(inclusive of both clinical and social medicine) versus the narrow control over
it is obvious in private health-care. However, this contradiction is present to
some extent, in its own way, even in the public health facilities in India. To
formulate a program for health-care for all in India, it is necessary to grasp
these contradictions in both private and public health-care and accordingly
conceptualize a strategy to overcome, resolve these contradictions.
PMID- 24351385
TI - Universal health care: the changing international discourse.
AB - Nearly 34 years ago, in 1978 in the face of a looming crisis in the health of the
world's populations and rising health inequality, 134 countries came together to
sign the historic Alma Ata Declaration where the idea of primary health care as
the chosen path to "Health for All" was formulated. However even before the
declaration and more so since, countries have diverse interpretations of
Universalism, each setting it in the context of its own health care model. These
have ranged from the minimalist to the more comprehensive welfare state. Today,
as health statistics reveal, the crisis has deepened, not only in the developing
world but also in the developed world. It is important to debate the nature of
the crisis and understand current policy initiatives and their ideological
legitimations. The paper attempts to trace, clarify and account for the shifts in
international discourse on universal health care (UHC). It argues that the idea
of UHC is still with us, but there have occurred substantial shifts in discourse
and meaning, shaped by changing international and national contexts and social
forces impinging on health systems. The current concept of universal health
coverage has only a notional allusion to universality of Alma Ata and disregards
its fundamental principles. It concludes that the shifts are detrimental and its
value in promoting health for all is likely to be severely limited.
PMID- 24351386
TI - Universal health care: pathways from access to utilization among vulnerable
populations.
AB - The present paper discusses universal access to health-care in the light of the
barriers faced by some vulnerable individuals and groups due to caste based
identities. Factors such as perception of self, availability of services,
sensitivity of the providers determine access and consequently affect utilization
among vulnerable populations. The paper examines the inter-linkages between these
factors. Efforts, which create enabling environment have been discussed to
highlight impeding and enhancing factors, Field based research has been used to
reflect on some of these factors and possible best practices.
PMID- 24351387
TI - Universalizing health services in India: the techno-managerial fix.
AB - The non-universal nature of health services in India can also be the result of
many reforms and milestones the health services had passed through since
independence. The reform era during the post-nineties is replete with many new
trends in organizational strategies which could have led to crises in health
services. The salient crises need to be dissected from a larger societal crisis
and the specific crises in the health services system. It is evident that non
accessibility and non-availability and the sub-optimal functioning of the primary
health centers are perennial issues which could not be addressed by indigenous,
imposed or cocktail reforms (such as National Rural Health Mission) and by
targeting as these only tinker with the health services. Needless to reiterate
that there is a need to address the social dimensions which fall outside the
technical sphere of health services. This paper based on an analytical review of
relevant literature concludes that any efforts to universalize health and health
care can not only focus on technical components but need to address the larger
social determinants and especially the societal crisis, which engender ill
health.
PMID- 24351388
TI - Rajiv Aarogyasri Community Health Insurance Scheme in Andhra Pradesh, India: a
comprehensive analytic view of private public partnership model.
AB - The Rajiv Aarogyasri Community Health Insurance (RACHI) in Andhra Pradesh (AP)
has been very popular social insurance scheme with a private public partnership
model to deal with the problems of catastrophic medical expenditures at tertiary
level care for the poor households. A brief analysis of the RACHI scheme based on
officially available data and media reports has been undertaken from a public
health perspective to understand the nature and financing of partnership and the
lessons it provides. The analysis of the annual budget spent on the surgeries in
private hospitals compared to tertiary public hospitals shows that the current
scheme is not sustainable and pose huge burden on the state exchequers. The
private hospital association's in AP, further acts as pressure groups to increase
the budget or threaten to withdraw services. Thus, profits are privatized and
losses are socialized.
PMID- 24351389
TI - Dimensions of nutritional vulnerability: assessment of women and children in
Sahariya tribal community of Madhya Pradesh in India.
AB - BACKGROUND: Tribal communities are "at risk" of undernutrition due to
geographical isolation and suboptimal utilization of health services. OBJECTIVES:
The objective of this study was to assess the nutritional status of Sahariya
tribes of Madhya Pradesh (MP), India. MATERIALS AND METHODS: A cross-sectional
study was conducted in villages inhabited by Sahariya tribal community
(specifically women in reproductive age group and children under 5 years) in
three districts of MP. Dietary surveys, anthropometric and biochemical
assessments were carried out and descriptive statistics on the socio-economic and
nutritional profile were reported. Association between household (HH) food
security and nutritional status of children was carried out using the logistic
regression. Strength of effects were summarized by odd's ratio. RESULTS: Chronic
energy deficiency and anemia was observed in 42.4% and 90.1% of women
respectively. Underweight, stunting and wasting among under five children were
59.1%, 57.3% and 27.7% respectively. Low food security was found in 90% of HHs
and the odds of children being underweight and stunted when belonging to HHs with
low and very low food security was found to be significant (P = 0.01 and 0.04
respectively). Calorie, fat, vitamin A, riboflavin, vitamin C and folic acid
intake among women was lower than recommended dietary allowance. Infant and young
child feeding practices were suboptimal. Awareness on nutritional disorders and
utilization of nutrition and health services was poor. CONCLUSION: A high
prevalence of undernutrition and dietary deficiency exists among Sahariyas.
System strengthening, community empowerment and nutrition education may play a
pivotal role in addressing this.
PMID- 24351390
TI - Factors associated with the preference for delivery at the government hospitals
in rural areas of Lucknow district in Uttar Pradesh.
AB - For assuring safe maternal and newborn health, institutional delivery was given
paramount importance. In India, in spite of several efforts, lesser than 40%
deliveries are conducted at health facilities, mostly at private sector. The
present cross-sectional study aimed to find out the determinants of preference
for delivery at government hospitals in rural areas of Lucknow, a district in
Uttar Pradesh. Multistage random sampling was used for selecting villages. From
them, 352 recently delivered women were selected, following systematic random
sampling. Overall, 84.9% of deliveries were conducted at health institutions. Out
of them, 79.3% were at government hospitals. Applying multivariate logistic
regression, Hindu women (odd's ratio [OR] = 3.205), women belonging to lower
socio-economic class (OR = 4.630) and late registered women (OR = 2.320) were
found to be more likely to deliver at government hospitals. Attention should be
given to religion, social status and timing of registration for ensuring higher
fraction of deliveries at government set-up.
PMID- 24351391
TI - Measles outbreak among the Dukpa tribe of Buxa hills in West Bengal, India:
epidemiology and vaccine efficacy.
AB - Although measles is a vaccine preventable disease, its occurrence and outbreaks
are common in India. Four remote and inaccessible hamlets, inhabited by the Dukpa
tribe, at Buxa Hills under Kalchini Block of Jalpaiguri District, West Bengal
experienced a measles outbreak during the months of April-June, 2011. The authors
conducted an investigation to assess vaccine coverage, vaccine efficacy (VE) and
to describe the patterns of measles outbreaks in this community. The over-all
attack rate was 14.3%; that among males and females were 12.6% and 16.0%
respectively (P = 0.189). Attack rate was highest (40%) in 0 to <5 years followed
by that in the 5 to <15 years (36.5%). VE was 66.3% (95% of the confidence
interval 46.9-78.6%). There is an urgent need to increase the vaccination
coverage through special tactics for reaching the unreached.
PMID- 24351392
TI - Use of insecticide-treated bednets in an urban coastal area of Puducherry, India:
a cross-sectional study.
AB - Use of Insecticide-Treated Bednets (ITNs) has been shown to reduce the incidence
of mosquito-borne diseases. However, the impact of ITNs depends on its community
acceptance. We studied the ITN usage and factors influencing it, following the
distribution of one ITN to each family in an urban area of Puducherry. Around
93.6% of the 157 respondents surveyed were aware of mosquito-borne diseases.
Coils and vaporizers were used in 91.1% of the families. Around two-fifths
(41.3%) of the 116 families who received the ITNs used it regularly with another
5.1% using it irregularly. Majority of the users (85%) reported reduced mosquito
bites and pleasant sleep after use. Small size of ITNs was the most common reason
for non-use (46.3%). Families not using normal bed nets at the time of
distribution of ITNs were unlikely to use ITNs at present (odds ratio = 5.22, P <
0.001). Therefore, ITN size should be increased and distribution in urban
settings should accompany behavior change communication.
PMID- 24351393
TI - Overuse of non-evidence based pharmacotherapies in coronary heart disease in
India.
PMID- 24351394
TI - Etiology of non-typical suicide patterns essential.
PMID- 24351395
TI - Status of reporting at health sub-center level in Bihar.
PMID- 24351396
TI - An optimized interatomic potential for Cu-Ni alloys with the embedded-atom
method.
AB - We have developed a semi-empirical and many-body type model potential using a
modified charge density profile for Cu-Ni alloys based on the embedded-atom
method (EAM) formalism with an improved optimization technique. The potential is
determined by fitting to experimental and first-principles data for Cu, Ni and Cu
Ni binary compounds, such as lattice constants, cohesive energies, bulk modulus,
elastic constants, diatomic bond lengths and bond energies. The generated
potentials were tested by computing a variety of properties of pure elements and
the alloy of Cu, Ni: the melting points, alloy mixing enthalpy, lattice specific
heat, equilibrium lattice structures, vacancy formation and interstitial
formation energies, and various diffusion barriers on the (100) and (111)
surfaces of Cu and Ni.
PMID- 24351397
TI - Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of
two randomised trials.
AB - BACKGROUND: Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated
the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over
gemcitabine (Gem) alone for patients with pathologically proven advanced biliary
tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This
pre-planned analysis evaluates the efficacy of CisGem with increased statistical
power. PATIENTS AND METHODS: We carried out a meta-analysis of individual patient
level data of these studies to establish the effect of CisGem versus Gem on
progression-free survival (PFS), overall survival (OS) and carried out
exploratory subgroup analyses. RESULTS: CisGem demonstrates a significant
improvement in PFS [hazard ratio (HR)=0.64, 95% confidence interval (CI) 0.53
0.76, P<0.001] and OS (HR=0.65, 95% CI 0.54-0.78, P<0.001) over Gem. This effect
is most marked among patients with good performance status (PS 0-1): HR for PFS
is 0.61 (95% CI 0.51-0.74), P<0.001 and OS HR=0.64 (95% CI 0.53-0.77), P<0.001.
CisGem resulted in improved PFS and OS for intra- and extra-hepatic
cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and
Japanese patients was consistent with respect to OS (HR=0.65, 95% CI 0.53-0.79
and 0.65, 95% CI 0.42-1.03, respectively); with similar OS in the combination
arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to
benefit included patients with ampullary tumours and poor performance status
(PS2). CONCLUSIONS: CisGem is the standard of care for the first-line treatment
of good-PS patients with advanced BTC regardless of ethnicity. Future studies
should aim to enhance the effectiveness of this regimen in the first-line
setting, establish the role of subsequent (second-line) therapy and assess the
role of rationally developed molecular-targeted therapies.
PMID- 24351398
TI - Maintenance strategies in stage IV non-small-cell lung cancer (NSCLC): in which
patients, with which drugs?
AB - Four to six cycles of platinum-based chemotherapy are currently recommended for
the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Several
studies have assessed the benefit of maintenance therapy following platinum-based
first-line therapy, to improve disease control, and thus, progression-free and
overall survival with minimal toxicity and maintenance or improvement of quality
of life of patients. We review here clinical trials evaluating continuation
maintenance therapy or switch maintenance therapy in locally advanced or
metastatic NSCLC, to highlight the achievements made and critical issues faced.
Based on the available results and limitations of these trials, maintenance
therapy should be considered a good treatment strategy for a limited subgroup of
patients. Maintenance therapy should be personalised according to the
characteristics of patients and their disease, taking into account the data
available for the agents used in this setting.
PMID- 24351399
TI - Long-term treatment efficacy in primary inflammatory breast cancer by hormonal
receptor- and HER2-defined subtypes.
AB - BACKGROUND: Subtypes defined by hormonal receptor (HR) and HER2 status have not
been well studied in inflammatory breast cancer (IBC). We characterized clinical
parameters and long-term outcomes, and compared pathological complete response
(pCR) rates by HR/HER2 subtype in a large IBC patient population. We also
compared disease-free survival (DFS) and overall survival (OS) between IBC
patients who received targeted therapies (anti-hormonal, anti-HER2) and those who
did not. PATIENTS AND METHODS: We retrospectively reviewed the records of
patients diagnosed with IBC and treated at MD Anderson Cancer Center from January
1989 to January 2011. Of those, 527 patients had received neoadjuvant
chemotherapy and had available information on estrogen receptor (ER),
progesterone receptor (PR), and HER2 status. HR status was considered positive if
either ER or PR status was positive. Using the Kaplan-Meier method, we estimated
median DFS and OS durations from the time of definitive surgery. Using the Cox
proportional hazards regression model, we determined the effect of prognostic
factors on DFS and OS. Results were compared by subtype. RESULTS: The overall pCR
rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype
showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the
highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast
cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of
HER2 status, had poor prognosis that did not differ from that of the HR
negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no
evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and
radiotherapy were associated with longer DFS and OS. CONCLUSIONS: Hormone
receptor and HER2 molecular subtypes had limited predictive and prognostic power
in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR
positive status did not necessarily confer a good prognosis. For all IBC
subtypes, novel, specific treatment strategies are needed in the neoadjuvant and
adjuvant settings.
PMID- 24351400
TI - Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT
in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone
marrow biopsy still necessary?
AB - BACKGROUND: This study aimed to systematically review and meta-analyze published
data on the diagnostic performance of (18)F-fluoro-2-deoxy-d-glucose positron
emission tomography/computed tomography (FDG-PET/CT) in detecting bone marrow
involvement in newly diagnosed Hodgkin lymphoma, and to determine whether FDG
PET/CT can replace blind bone marrow biopsy (BMB) in these patients. PATIENTS AND
METHODS: The PubMed/Medline and Embase databases were systematically searched for
relevant studies. Methodological quality of each study was assessed.
Sensitivities and specificities of FDG-PET/CT in individual studies were
calculated and underwent meta-analysis with a random effects model. A summary
receiver operating characteristic curve (sROC) was constructed with the Moses
Shapiro-Littenberg method. The weighted summary proportion of FDG-PET/CT-negative
patients with a positive BMB among all cases was calculated under the fixed
effects model. RESULTS: Nine eligible studies, comprising a total of 955 patients
with newly diagnosed Hodgkin lymphoma, were included. Overall, the studies were
of moderate methodological quality. The sensitivity and specificity of FDG-PET/CT
for the detection of bone marrow involvement ranged from 87.5% to 100% and from
86.7% to 100%, respectively, with pooled estimates of 96.9% [95% confidence
interval (CI) 93.0% to 99.0%] and 99.7% (95% CI 98.9% to 100%), respectively. The
area under the sROC curve was 0.9860. The weighted summary proportion of FDG
PET/CT-negative patients with a positive BMB among all cases was 1.1% (95% CI
0.6% to 2.0%). CONCLUSION: Although the methodological quality of studies that
were included in this systematic review and meta-analysis was moderate, the
current evidence suggests that FDG-PET/CT may be an appropriate method to replace
BMB in newly diagnosed Hodgkin lymphoma.
PMID- 24351401
TI - Present and future breast cancer management--bench to bedside and back: a
positioning paper of academia, regulatory authorities and pharmaceutical
industry.
AB - Insights into tumour biology of breast cancer have led the path towards the
introduction of targeted treatment approaches; still, breast cancer-related
mortality remains relatively high. Efforts in the field of basic research
revealed new druggable targets which now await validation within the context of
clinical trials. Therefore, questions concerning the optimal design of future
studies are becoming even more pertinent. Aspects such as the ideal end point,
availability of predictive markers to identify the optimal cohort for drug
testing, or potential mechanisms of resistance need to be resolved. An expert
panel representing the academic community, the pharmaceutical industry, as well
as European Regulatory Authorities met in Vienna, Austria, in November 2012, in
order to discuss breast cancer biology, identification of novel biological
targets and optimal drug development with the aim of treatment individualization.
This article summarizes statements and perspectives provided by the meeting
participants.
PMID- 24351402
TI - A randomized multicenter phase II trial on the efficacy of a hydrocolloid
dressing containing ceramide with a low-friction external surface for hand-foot
skin reaction caused by sorafenib in patients with renal cell carcinoma.
AB - BACKGROUND: The purpose of this study was to investigate the usefulness of a
hydrocolloid dressing containing ceramide for hand-foot skin reaction (HFSR) on
the soles of the feet in metastatic renal cell carcinoma (RCC) patients treated
with sorafenib. PATIENTS AND METHODS: Patients with grade 1 HFSR on the soles of
the feet were randomly assigned in to two groups. One group received a
hydrocolloid dressing containing ceramide (arm A) and the other received 10% urea
cream (arm B). Patients in both groups applied treatment to the affected sites on
the soles of the feet, but not to the hands. The primary end point was the
incidence of grade 2 or 3 HFSR on the soles of the feet in the first 4 weeks.
RESULTS: Thirty-three patients were assessed (17 in arm A and 16 in arm B), and
there were no significant differences in baseline characteristics between the two
groups. During the observation period of this study, grade 2 or 3 HFSR on the
soles of the feet was found in 29% of patients in arm A and was significantly
less than the 69% in arm B (P=0.03). The incidence of HFSR on the hands, however,
was similar in both arms. The median time to grade 2 or 3 HFSR on the soles of
the feet was also significantly longer in arm A than in arm B (P=0.03).
CONCLUSIONS: These results indicate that a hydrocolloid dressing containing
ceramide prevented the worsening of HFSR caused by sorafenib in metastatic RCC
patients. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000002016.
PMID- 24351403
TI - Association of molecular subtypes with Ki-67 changes in untreated breast cancer
patients undergoing pre-surgical trials.
AB - BACKGROUND: Ki-67 is increasingly being used as a response biomarker in window of
opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often
higher at surgery than at baseline core biopsy in subjects allocated to placebo,
we investigated which factors affected this change. PATIENTS AND METHODS: We
retrieved data from 274 patients who received no active treatment in three
consecutive pre-surgical trials from a single institution. We assessed the
association between changes in Ki-67 from diagnostic biopsy to surgical specimen
and the following factors: age, body mass index, tumor prognostic and predictive
factors, including immunohistochemical molecular subtype, number and size of
biopsy specimens, time from biopsy to surgery, circulating insulin-like growth
factor-I, sex hormone-binding globulin and hsCRP. RESULTS: A total of 269
patients with paired measures of Ki-67 at biopsy and surgery were analyzed.
Overall, the mean (+/-SD) change was 2.2 +/- 9.2% after a median interval of 41
days (inter-quartile range 33-48). Molecular subtype was the only factor
associated with a significant change of Ki-67 (P = 0.004), with a mean absolute
increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen
receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P <
0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n
= 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was
observed. CONCLUSIONS: A significant increase in Ki-67 from baseline biopsy to
end point surgery in untreated subjects was ascertained in HER2-positive and
triple-negative tumors. This biological association suggests a real increase in
cancer proliferation, possibly as a result of a biopsy-driven wound healing
effect, and should be considered in the design and interpretation of pre-surgical
studies. REGISTERED CLINICAL TRIAL NUMBERS: ISRCTN86894592; ISRCTN16493703.
PMID- 24351404
TI - Pharmacogenetic predictors of severe peripheral neuropathy in colon cancer
patients treated with oxaliplatin-based adjuvant chemotherapy: a GEMCAD group
study.
AB - BACKGROUND: Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy
for stage III and selected high-risk stage II colon cancer (CC) patients, is
often associated with cumulative peripheral neuropathy. Our aim is to identify
single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin
metabolism, DNA repair mechanisms, cell cycle control, detoxification or
excretion pathways to predict severe (grade 2-3) oxaliplatin-induced peripheral
neuropathy (OXPN) among CC patients treated with oxaliplatin and fluoropyrimidine
based adjuvant CT. PATIENTS AND METHODS: Genomic DNA was extracted from formalin
fixed-paraffin-embedded peritumoral samples from 206 high-risk stage II and stage
III CC patients receiving oxaliplatin-based adjuvant CT from January 2004 to
December 2009. Genotyping was carried out for 34 SNPs in 15 genes using MassARRAY
(SEQUENOM) technology. A total of 181 stage II-III CC patients treated with the
same CT regimens were enrolled as a validation set. RESULTS: The rs2230641 cyclin
H (CCNH) rs2230641 C/C [odd ratio (OR)=5.03, 95% confidence interval (CI) 1.061
2.41, P=0.042] and the ATP-binding cassette subfamily G, member 2 (ABCG2)
rs3114018 A/A genotypes (OR=2.67; 95% CI 0.95-4.41; P=0.059) were associated with
a higher risk of severe OXPN. In addition, patients harboring the combination of
CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes had a higher risk of grade 2-3
OXPN than those with the CCNH any T and ABCG2 any C genotypes (37.73% versus
19.42%; OR=2.46; 95% CI 1.19-5.07; P=0.014) in the logistic regression analysis
using age, gender, adjuvant CT regimen and cumulative dose of oxaliplatin as
covariates. The ability to predict severe OXPN of this combined analysis was
independently validated in the second cohort (58% versus 33.33%; OR=2.99; 95% CI
1.45-6.13; P=0.002). CONCLUSIONS: Our results suggest that SNPs in CCNH and ABCG2
can modulate the development of severe OXPN among stage II-III CC patients who
received oxaliplatin-based CT, thus enabling the individualization of adjuvant
treatment.
PMID- 24351409
TI - Dose uncertainties in IMPT for oropharyngeal cancer in the presence of
anatomical, range, and setup errors.
AB - PURPOSE: Setup, range, and anatomical uncertainties influence the dose delivered
with intensity modulated proton therapy (IMPT), but clinical quantification of
these errors for oropharyngeal cancer is lacking. We quantified these factors and
investigated treatment fidelity, that is, robustness, as influenced by adaptive
planning and by applying more beam directions. METHODS AND MATERIALS: We used an
in-house treatment planning system with multicriteria optimization of pencil beam
energies, directions, and weights to create treatment plans for 3-, 5-, and 7
beam directions for 10 oropharyngeal cancer patients. The dose prescription was a
simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and
positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to
elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of
setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans
were used to evaluate an adaptive planning strategy using nonrigid registration
for dose accumulation. RESULTS: For the recalculated 3-beam plans including all
treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the
simulations had a dose received by 98% of the target volume (D98%) >95% of the
prescription dose. Doses to organs at risk (OARs) showed considerable spread
around planned values. Causes for major deviations were mixed. Adaptive planning
based on repeat imaging positively affected dose delivery accuracy: in the
presence of the other errors, percentages of treatments with D98% >95% increased
to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not
more robust. CONCLUSIONS: For oropharyngeal cancer patients, treatment
uncertainties can result in significant differences between planned and delivered
IMPT doses. Given the mixed causes for major deviations, we advise repeat
diagnostic CT scans during treatment, recalculation of the dose, and if required,
adaptive planning to improve adequate IMPT dose delivery.
PMID- 24351410
TI - Localization accuracy and immobilization effectiveness of a stereotactic body
frame for a variety of treatment sites.
AB - PURPOSE: The purpose of this study was to analyze the pretreatment setup errors
and intrafraction motion using cone beam computed tomography (CBCT) for
stereotactic body radiation therapy patients immobilized and localized with a
stereotactic body frame for a variety of treatment sites. METHODS AND MATERIALS:
Localization errors were recorded for patients receiving SBRT for 141 lung, 29
liver, 48 prostate, and 45 spine tumors representing 1005 total localization
sessions. All patients were treated in a stereotactic body frame with a large
custom-molded vacuum pillow. Patients were first localized to the frame using
tattoos placed during simulation. Subsequently, the frame was aligned to the room
lasers according to the stereotactic coordinates determined from the treatment
plan. Every patient received a pretreatment and an intrafraction CBCT. Abdominal
compression was used for all liver patients and for approximately 40% of the lung
patients to reduce tumor motion due to respiration. RESULTS: The mean +/-
standard deviation pretreatment setup errors from all localizations were -2.44 +/
3.85, 1.31 +/- 5.84, and 0.11 +/- 3.76 mm in the anteroposterior,
superoinferior, and lateral directions, respectively. The mean pretreatment
localization results among all treatment sites were not significantly different
(F test, P<.05). For all treatment sites, the mean +/- standard deviation
intrafraction shifts were 0.33 +/- 1.34, 0.15 +/- 1.45, and -0.02 +/- 1.17 mm in
the anteroposterior, superoinferior, and lateral directions, respectively. The
mean unidimensional intrafraction shifts were statistically different for several
of the comparisons (P<.05) as assessed by the Tukey-Kramer test. CONCLUSIONS:
Despite the varied tumor locations, the pretreatment mean localization errors for
all sites were found to be consistent among the treatment sites and not
significantly different, indicating that the body frame is a suitable
immobilization and localization device for a variety of tumor sites. Our
pretreatment localization errors and intrafraction shifts compare favorably with
those reported in other studies using different types of immobilization devices.
PMID- 24351411
TI - Patterns and predictors of early biochemical recurrence after radical
prostatectomy and adjuvant radiation therapy in men with pT3N0 prostate cancer:
implications for multimodal therapies.
AB - PURPOSE: The aim of our study was to evaluate patterns and predictors of early
biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant
radiation therapy (aRT) in order to identify which individuals might benefit from
additional treatments. METHODS AND MATERIALS: We evaluated 390 patients with
pT3N0 prostate cancer (PCa) receiving RP and aRT at 6 European centers between
1993 and 2006. Patients who were free from BCR at <2 years' follow-up were
excluded. This resulted in 374 assessable patients. Early BCR was defined as 2
consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3
years after aRT. Uni- and multivariable Cox regression analyses predicting
overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA
results, surgical margins, pathological stage, Gleason score, and aRT dose.
RESULTS: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%,
respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55
(14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In
multivariable analyses, Gleason scores of 8 to 10 represented the only
independent predictor of eBCR after aRT (all, P<=.01). The risk of BCR was
significantly higher in patients with a Gleason score of 8 to 10 disease than in
those with Gleason 2 to 6 within 24 months after treatment, after adjusting for
all covariates (all, P<=.04). However, given a 24-month BCR free period, the risk
of subsequent BCR for men with poorly differentiated disease was equal to that of
men with less aggressive disease (all, P>=.3). CONCLUSIONS: High Gleason score
represents the only predictor of eBCR after RP and aRT in patients affected by
pT3N0 PCa. Given the association between early PSA recurrence, clinical
progression, and mortality, these patients might be considered candidates for
adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in
addition to aRT, delivered to the prostatic bed.
PMID- 24351412
TI - Mesenchymal stem cells retain their defining stem cell characteristics after
exposure to ionizing radiation.
AB - PURPOSE: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion
sites and undergo differentiation into functional tissues. Although this function
may be important for tissue regeneration after radiation therapy, the influence
of ionizing radiation (IR) on cellular survival and the functional aspects of
differentiation and stem cell characteristics of MSCs have remained largely
unknown. METHODS AND MATERIALS: Radiation sensitivity of human primary MSCs from
healthy volunteers and primary human fibroblast cells was examined, and cellular
morphology, cell cycle effects, apoptosis, and differentiation potential after
exposure to IR were assessed. Stem cell gene expression patterns after exposure
to IR were studied using gene arrays. RESULTS: MSCs were not more radiosensitive
than human primary fibroblasts, whereas there were considerable differences
regarding radiation sensitivity within individual MSCs. Cellular morphology,
cytoskeletal architecture, and cell motility were not markedly altered by IR.
Even after high radiation doses up to 10 Gy, MSCs maintained their
differentiation potential. Compared to primary fibroblast cells, MSCs did not
show an increase in irradiation-induced apoptosis. Gene expression analyses
revealed an upregulation of various genes involved in DNA damage response and DNA
repair, but expression of established MSC surface markers appeared only
marginally influenced by IR. CONCLUSIONS: These data suggest that human MSCs are
not more radiosensitive than differentiated primary fibroblasts. In addition,
upon photon irradiation, MSCs were able to retain their defining stem cell
characteristics both on a functional level and regarding stem cell marker
expression.
PMID- 24351418
TI - Prevalence of interatrial block in patients undergoing coronary bypass graft
surgery.
PMID- 24351419
TI - Double or split right coronary artery: still a diagnostic dilemma for this rare
coronary anomaly.
PMID- 24351420
TI - Perceived barriers and facilitators of using a Web-based interactive decision aid
for colorectal cancer screening in community practice settings: findings from
focus groups with primary care clinicians and medical office staff.
AB - BACKGROUND: Information is lacking about the capacity of those working in
community practice settings to utilize health information technology for
colorectal cancer screening. OBJECTIVE: To address this gap we asked those
working in community practice settings to share their perspectives about how the
implementation of a Web-based patient-led decision aid might affect patient
clinician conversations about colorectal cancer screening and the day-to-day
clinical workflow. METHODS: Five focus groups in five community practice settings
were conducted with 8 physicians, 1 physician assistant, and 18 clinic staff.
Focus groups were organized using a semistructured discussion guide designed to
identify factors that mediate and impede the use of a Web-based decision aid
intended to clarify patient preferences for colorectal cancer screening and to
trigger shared decision making during the clinical encounter. RESULTS: All
physicians, the physician assistant, and 8 of the 18 clinic staff were active
participants in the focus groups. Clinician and staff participants from each
setting reported a belief that the Web-based patient-led decision aid could be an
informative and educational tool; in all but one setting participants reported a
readiness to recommend the tool to patients. The exception related to clinicians
from one clinic who described a preference for patients having fewer screening
choices, noting that a colonoscopy was the preferred screening modality for
patients in their clinic. Perceived barriers to utilizing the Web-based decision
aid included patients' lack of Internet access or low computer literacy, and
potential impediments to the clinics' daily workflow. Expanding patients' use of
an online decision aid that is both easy to access and understand and that is
utilized by patients outside of the office visit was described as a potentially
efficient means for soliciting patients' screening preferences. Participants
described that a system to link the online decision aid to a computerized
reminder system could promote a better understanding of patients' screening
preferences, though some expressed concern that such a system could be difficult
to keep up and running. CONCLUSIONS: Community practice clinicians and staff
perceived the Web-based decision aid technology as promising but raised questions
as to how the technology and resultant information would be integrated into their
daily practice workflow. Additional research investigating how to best implement
online decision aids should be conducted prior to the widespread adoption of such
technology so as to maximize the benefits of the technology while minimizing
workflow disruptions.
PMID- 24351421
TI - Complex mixtures of antibodies generated from a single production qualitatively
and quantitatively evaluated by native Orbitrap mass spectrometry.
AB - Composite antibody mixtures designed to combat diseases present a new, rapidly
emerging technology in the field of biopharmaceuticals. The combination of
multiple antibodies can lead to increased effector response and limit the effect
of escape variants that can propagate the disease. However, parallel development
of analytical technologies is required to provide fast, thorough, accurate, and
robust characterization of these mixtures. Here, we evaluate the utility of
native mass spectrometry on an Orbitrap platform with high mass resolving power
to characterize composite mixtures of up to 15 separate antibodies. With this
technique, unambiguous identification of each antibody in the mixtures was
achieved. Mass measurements of the intact antibodies varied 7 ppm on average,
allowing highly reproducible identification and quantitation of each compound in
these complex mixtures. We show that with the high mass-resolving power and
robustness of this technology, high-resolution native mass spectrometry can be
used efficiently even for batch-to batch characterization.
PMID- 24351422
TI - Evaluating the concordance of physician judgments and patient preferences on
AIDS/HIV therapy - a Discrete Choice Experiment.
AB - OBJECTIVES: Patient-centered health care and shared decision making are of
increasing importance in the management of AIDS/HIV patients and require an
intensive consideration of patient preferences. The present study assesses
expectations and needs of patients from the physician point of view. The aim of
this study was to compare patient and physician perspectives of relevant aspects
of treatment quality such as effectiveness, quality of life and further treatment
options. METHODS: The study was performed as an anonymous survey including German
physicians. Physicians treating large numbers of AIDS/HIV patients were
preferably contacted. The physicians were asked to assess their view of patient
preferences of therapy characteristics using direct measurement, as well as by
means of a Discrete Choice Experiment (DCE). The questionnaire was adopted from a
previous study in which AIDS/HIV patients were asked to assess their treatment
preferences. RESULTS: 131 physicians completed the questionnaire, 88% of these on
paper and 12% online. 70% of the physicians were male. The mean duration since
licensure was 17 years. The most frequent specialist areas were internal medicine
(N = 55), infectiology (N = 31) and general medicine (N = 27). In the direct
measurement the most relevant therapy characteristics were "drug does not affect
or not affect appearance much", "self-application of the drug is possible" and
"rarely occurring longer periods of nausea and diarrhea". Six treatment
characteristics were selected and used to generate eight virtual pairs of
therapies. To evaluate the assessments a random effect logit model was employed.
In view of the physicians avoidance of an obvious perceptibility of the disease
the emotional quality of life had by far the strongest impact on the patients'
treatment preferences as rated by physicians. With some distance the physical
quality of life with less diarrhea or nausea, as well as the possibility to
participate in social life followed on the same level. CONCLUSIONS: Discrete
Choice Experiment proved to be a valid survey technique in the evaluation of
AIDS/HIV treatment preferences as assessed by patients and by physicians
assessing the view of their patients. Covering a broad range of treatment
characteristics, the physician assessments of preferences were very close to
those of AIDS/HIV patients emphasizing the high impact of quality of life, in
particular the emotional quality of life on patient preferences in the selection
of treatments. Thus, the selection of particular treatment options should be
accompanied by a deliberate consideration of treatment features, which need to be
considered in order to maximize patient adherence and compliance.
PMID- 24351423
TI - HDAC inhibitors enhance the lethality of low dose salinomycin in parental and
stem-like GBM cells.
AB - The present studies determined whether the antibiotic salinomycin interacted with
HDAC inhibitors to kill primary human GBM cells. Regardless of PTEN, ERBB1, or
p53 mutational status salinomycin interacted with HDAC inhibitors in a
synergistic fashion to kill GBM cells. Inhibition of CD95/Caspase 8 or of
CD95/RIP-1/AIF signaling suppressed killing by the drug combination. Salinomycin
increased the levels of autophagosomes that correlated with increased p62 and
LC3II levels; valproate co-treatment correlated with reduced LC3II and p62
expression, and increased caspase 3 cleavage. Molecular inhibition of
autophagosome formation was protective against drug exposure. The drug
combination enhanced eIF2alpha phosphorylation and decreased expression of MCL-1
and phosphorylation of mTOR and p70 S6K. Activation of p70 S6K or mTOR promoted
cell survival in the face of combined drug exposure. Overexpression of BCL-XL or
c-FLIP-s was protective. Collectively our data demonstrate that the lethality of
low nanomolar concentrations of salinomycin are enhanced by HDAC inhibitors in
GBM cells and that increased death receptor signaling together with reduced
mitochondrial function are causal in the combinatorial drug necro-apoptotic
killing effect.
PMID- 24351426
TI - The clinical effectiveness of weight loss drugs.
AB - SUMMARY: At a time when obesity is reaching epidemic proportions across the
western world and increasing rapidly in developing countries, clinicians clearly
are becoming more aware of the need to offer weight management advice and
effective treatment to patients, especially those with a high risk of developing
type 2 diabetes. For those patients with a BMI >= 30.0 kg/m(2) or for those with
a BMI of 27.0 kg/m(2) with an obesity-related disease such as dyslipidaemia or
type 2 diabetes mellitus, modest weight loss in the order of 5% achieved by
modification of dietary intake and activity behaviour can significantly improve
risk factors for obesity-related diseases and delay progression to type 2
diabetes. Unfortunately, rates of adherence with dietary-based weight management
programmes are generally low and for most patients weight regain with time is
common. The use of weight loss medications is recognised as a positive strategy
for helping patients adhere to lifestyle advice, and has been shown to result in
clinically significant and meaningful improvement of symptoms, risk factors and
quality of life. Appropriate selection and use of weight management drugs
requires an understanding of the benefits and risks associated with each of the
available drugs. Clinical trials are ongoing to determine whether weight
management interventions (including anti-obesity pharmacotherapy) will impact
upon clinical outcome and life expectancy.:
PMID- 24351424
TI - The frequency and outcome of uveitis in patients with newly diagnosed juvenile
idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.
AB - OBJECTIVES: To retrospectively compare the frequency and outcome of uveitis
between two cohorts of patients with newly-onset juvenile idiopathic arthritis
(JIA) separated by a 10 year interval. METHODS: The diagnosis of JIA was made in
239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric
rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An
ophthalmologist examined all the patients regularly and diagnosed uveitis. The
demographics of the patients, type of JIA, frequency, medical treatment and
outcome of uveitis were documented. RESULTS: The main outcome measures were the
frequency and outcome of uveitis, the number of complications and the best
corrected visual acuity (BCVA), need of corticosteroids and other
immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in
the earlier cohort. The visual outcome was >=0.5 in all JIA-uveitis patients
except one in the earlier cohort. Complications were fewer (21% vs. 35%) and
uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN)
criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis
(20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow
up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more
commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the
use of methotrexate was equal in both cohorts (65% vs. 67%). CONCLUSIONS: In this
study with early and aggressive treatment and close monitoring the outcome of JIA
uveitis patients was favourable and visual loss was avoided in most cases.
PMID- 24351427
TI - Rapid significant weight loss and regional lipid deposition: Implications for
insulin sensitivity.
AB - SUMMARY: AIM: To compare regional lipid deposition and insulin sensitivity after
differing weight loss strategies: very low calorie diet (VLCD) and laparoscopic
adjustable gastric banding (LAGB). METHOD: Thirty-nine obese women underwent
anthropometry, proton magnetic resonance (MR) spectroscopy for assessment of
liver fat (LFAT) and MR imaging for visceral (VAT) and subcutaneous abdominal fat
volume (SAT) determination. Fasting blood was taken for insulin, glucose and free
fatty acid (FFA) analysis. Measurements were repeated after 6-weeks Optifast VLCD
(n = 14) or 3 months after LAGB (n = 25). RESULTS: Similar, significant (p <
0.001) weight loss occurred after VLCD (8%) and LAGB (9%). Both interventions
induced significant (p < 0.001) and similar reductions in body mass index (BMI)
and waist circumference, and in SAT and VAT (VLCD p < 0.05, LAGB p < 0.001). LFAT
fell only after VLCD (p < 0.05). Plasma FFA only fell after LAGB (p < 0.05).
Homeostasis model assessment (HOMA-R) improved only following VLCD (p < 0.05). No
relations were detected between the changes in LFAT, VAT and SAT. The change in
LFAT related to the change in HOMA-R in both interventions combined (r = 0.410, p
= 0.013) and in the VLCD group (r = 0.660, p = 0.020). There was no change in
relative dietary fat intake after LAGB (p = 0.11). CONCLUSION: Caloric and fat
restriction for 6 weeks (VLCD) reduces weight, SAT, VAT, LFAT and HOMA-R. Less
severe caloric restriction for 12 weeks (LAGB) causes significant loss of weight,
VAT and SAT but no detectable change in LFAT and HOMA-R. Following weight loss, a
change in LFAT is related more to changes in insulin sensitivity or dietary fat
than to abdominal adiposity loss.
PMID- 24351425
TI - ERK2-dependent reactivation of Akt mediates the limited response of tumor cells
with constitutive K-RAS activity to PI3K inhibition.
AB - K-RAS mutated (K-RASmut) non-small cell lung cancer (NSCLC) cells are resistant
to EGFR targeting strategies. We investigated the impact of K-RAS activity
irrespective of mutational status in the EGFR-independent increase in clonogenic
cell survival. An analysis of the K-RAS activity status revealed a constitutively
high K-RAS activity in K-RASmut NSCLC cells and also in head and neck squamous
cell carcinoma (HNSCC) cells overexpressing wild-type K-RAS (K-RASwt). Similar to
K-RAS-mutated cells, increased K-RAS activity in HNSCC cells overexpressing K
RASwt was associated with the stimulated production of the EGFR ligand
amphiregulin and resistance to EGFR tyrosine kinase (EGFR-TK) inhibitors such as
erlotinib. Expression of mutated K-RAS stimulated Akt phosphorylation and
increased plating efficiency. Conversely, knockdown of K-RAS in K-RASmut NSCLC
cells and in HNSCC cells presenting overexpression of K-RASwt resulted in
sensitization to the anti-clonogenic activity of erlotinib. K-RAS activity
results in EGFR-dependent and EGFR-independent Akt activity. The short-term
treatment (2 h) of cells with EGFR-TK or PI3K inhibitors (erlotinib and PI-103)
resulted in the repression of Akt activation, whereas long-term treatment (24 h)
with inhibitors led to the reactivation of Akt and improved clonogenicity. The
Akt re-activation was MAPK-ERK2-dependent and associated with a lack of complete
response to anti-clonogenic activity of PI-103. A complete response was observed
when PI-103 was combined with MEK inhibitor PD98059. Together, clonogenicity
inhibition in tumor cells presenting constitutive K-RAS activity independent of K
RAS mutational status can be achieved by targeting of EGFR downstream pathways,
i.e., PI3K alone or the combination of PI3K and MAPK inhibitors.
PMID- 24351428
TI - Identifying cut-points in anthropometric indexes for predicting previously
undiagnosed diabetes and cardiovascular risk factors in the Tongan population.
AB - SUMMARY: There is growing concern that a single standard definition of overweight
and obesity may not suit all ethnic groups. This study aimed to evaluate
different anthropometric cut-points as indicators of risk for Type 2 diabetes
(T2DM), hypertension and dyslipidaemia in a cross sectional, representative
sample of the population of the Kingdom of Tonga (767 subjects: 314 males, 453
females). Anthropometric measurements included weight, height, waist
circumference (WAIST), waist-to-hip ratio (WHR), weight-to-height ratio (WhgtR)
and percentage body fat (%fat) using bioelectrical impedance. Risk factors
investigated were systolic (sBP) and diastolic blood pressure (dBP), plasma
glucose, total cholesterol, HDL cholesterol and triglycerides, hypertension and
T2DM. The best predictive cut-points were identified using receiver operating
characteristic (ROC) curves. The cut-points identified in this cross-sectional
study contrast with those from studies in Caucasian and Asian populations.
Optimal cut-points for predicting risk for T2DM, dyslipidaemia and hypertension
in men were 29.3-31.7 kg/m(2) for BMI; 98.8-102.9 cm for WAIST; 0.91-0.93 for WHR
and 0.56-0.60 for WhgtR. For women, the cut-points were 34.0-35.0 kg/m(2) (BMI),
100.0-102.8 cm (WAIST), 0.83-0.86 (WHR) and 0.60-0.62 (WhgtR). Mean area under
the curve (AUC) measurements for each index ranged between 0.57 and 0.75 for men
and 0.49 and 0.72 for women. The indexes with the highest AUCs for men were
WAIST, WhgtR and BMI; and for women were WAIST and WhgtR. Use of a 100 cm tape
for measuring WAIST is recommended as a simple public health and clinical
indicator of risk until longitudinal follow-up studies can confirm findings of
this study.:
PMID- 24351430
TI - Disability in obese elderly women: Lower limb strength and recreational physical
activity.
AB - SUMMARY: CONTEXT: Disability in the obese may be a consequence of low muscle
strength and inactivity. OBJECTIVE: We compared isometric knee extensor strength
(KES) between obese (body mass index, BMI >29 kg/m(2)), normal (BMI [24-29]) and
lean (BMI < 24) elderly and its association with disability. Then, we
investigated the risk of disability in obese, normal, and lean participants
according to their physical activity. METHODS: 215 obese (80.0 +/- 3.5 y, BMI
31.9 +/- 2.6), 630 normal (80.2 +/- 3.7 y, BMI 26.3 +/- 1.4) and 598 lean (80.7
+/- 4.1 y, BMI 21.6 +/- 1.8) women with good functional ability were studied. A
cross-sectional design was used. Anthropometric measures, KES (statometers),
health status, self-reported difficulties for physical function, disability
(Instrumental and Basic Activity of Daily Living), and recreational physical
activities (RPA; walking, gymnastics, cycling, swimming, and gardening) were
obtained. RESULTS: KES was negatively and significantly associated with
disability and functional difficulties. When KES was adjusted for age, RPA, pain,
depression, visual impairment, steroid treatment, comorbidity, osteoporosis and,
weight, an interaction effect between the BMI groups and RPA (p = 0.01) was
found. KES significantly decreased in the sedentary women with increasing BMI but
was not significantly different in active (>=1 h/week in >=1 RPA for >=1 month)
women. Association between KES and self-reported difficulties for physical
function was significantly lower in the active compared to the sedentary women
and was not significantly higher in the active obese women. CONCLUSIONS: Low KES
is associated with disability and difficulties for physical function in elderly
women. The higher level of KES in participants engaged in RPA may prevent
disability related to obesity.
PMID- 24351429
TI - Adiponectin levels in obese and non-obese middle-aged African-American women.
AB - SUMMARY: CONTEXT: Adiponectin levels in African-Americans are poorly described.
OBJECTIVE: To assess predictors of serum adiponectin levels in obese and non
obese middle-aged African-American women. METHODS: Serum adiponectin,
testosterone (T), free androgen index (FAI), estradiol, dehydroepiandrosterone
sulfate (DHEAS), leptin, sex hormone binding globulin (SHBG), triglycerides and C
reactive protein (CRP) were measured in 142 obese and 102 non-obese, community
dwelling, African-American women in St. Louis, Missouri. Medical history,
physical activity, anthropometry, medications and body composition were assessed.
RESULTS: Adiponectin and SHBG levels were lower and leptin and CRP were higher in
obese compared to non-obese women (P's < 0.01). Overall, log adiponectin was
positively associated with age (R = 0.13) and log SHBG (R = 0.29), and inversely
associated with anthropometric measures (R's = -0.17 to -0.36), serum androgens
(R's = -0.21 to -0.23), log estradiol (R = -0.21), log leptin (R = -0.15), log
triglycerides (R = -0.33) and log CRP (R = -0.29). Overall, multivariate
modelling significantly predicted 32% of variation in adiponectin level; the most
significant factors were WHR (beta = -1.33), SHBG (beta = 0.23) and triglycerides
(beta = -0.34). In non-obese women, the model predicted 27% of variation in
adiponectin level; no individual factor was independently associated. In obese
women, the model predicted 30% of variation in adiponectin level; the most
significant factors were WHR (beta = -1.49), triglycerides (beta = -0.34) and
history of stroke (beta = -0.71). CONCLUSIONS: Adiponectin level in African
American women is predicted by WHR, SHBG, and triglycerides; stroke history adds
predictive value in obese women.
PMID- 24351431
TI - Leptin stimulation of COXIV is impaired in obese skeletal muscle myotubes.
AB - SUMMARY: OBJECTIVE: To investigate the effects of leptin on the mRNA abundance
of key genes involved in fatty acid oxidation and mitochondrial biogenesis in
cultured skeletal muscle myotubes derived from lean and obese individuals.
RESEARCH METHODS AND PROCEDURES: Rectus abdominus muscle biopsies were obtained
from surgical patients to establish primary skeletal muscle cell cultures. Two
distinct primary cell culture groups were established (Lean and Obese) n = 7 in
each group. Differentiated cultures were then exposed to leptin (2.5 MUg/ml) for
6 h. mRNA expression was subsequently measured by real-time PCR analysis.
RESULTS: Basal mRNA expression of betaHAD, COXIII, COXIV, PGC-1alpha and SOCS3 in
the cultured human skeletal muscle myotubes were similar, however, PDK4 mRNA was
elevated (P < 0.05) in the myotubes derived from obese individuals. The addition
of leptin resulted in a 2.5-fold increase in COXIV mRNA expression in the
myotubes derived from Lean individuals only (P < 0.05). There was also a tendency
for leptin to increase COXIII, betaHAD and PDK4 mRNA expression in this same
group. Leptin had no impact on the gene expression of all measured transcripts in
myotubes derived from obese individuals. CONCLUSION: Short-term exposure of human
skeletal muscle myotubes to leptin stimulated the expression of the mitochondrial
enzyme COXIV in myotubes derived from lean individuals, an effect that was
abrogated in myotubes derived from obese individuals. These data demonstrate a
novel capacity for leptin to increase mitochondrial biogenesis and thus, a
possible increased capacity for lipid oxidation and the persistence of a defect
in leptin signalling in human myotubes cultured from obese individuals.
PMID- 24351432
TI - Day-night difference in beta3-adrenoceptor agonist-induced energy expenditure:
Contribution of brown fat thermogenesis and physical activity.
AB - SUMMARY: beta3-adrenergic receptor (beta3-AR) agonist, a drug that reduces body
fat, stimulates lipomobilization from white adipose tissue (WAT) and
thermogenesis in brown adipose tissue (BAT). To test the day-night difference in
the effects of beta3-AR agonist, in the present study, we examined the responses
of lipomobilization and energy expenditure to CL316,243 (CL) during the daytime
at 10:00 and nighttime at 22:00 in mice kept in a 12 h light-dark cycle with
lights on from 07:00. CL injection increased plasma free fatty acid to the same
extent at 10:00 and 22:00. In contrast, CL injection increased total oxygen
consumption more markedly at 10:00 than 22:00. Physical activity was suppressed
by CL injection especially at 22:00. Correcting total oxygen consumption by the
suppressive effect on physical activity, oxygen consumption dependent on BAT
thermogenesis was estimated. This revealed that the effect of CL on BAT
thermogenesis was not different between 10:00 and 22:00. Thus, we concluded that
there is no day-night difference in the CL effects on lipomobilization from WAT
and thermogenesis in BAT. The stronger effect of CL on total energy expenditure
in the daytime was largely due to a more suppressive effect on physical activity
in the nighttime.:
PMID- 24351433
TI - In vivo quantification of fat content in mice using the Hologic QDR 4500A
densitometer.
AB - SUMMARY: PURPOSE: Validation of dual-energy X-ray absorptiometry (DXA) with the
Hologic QDR 4500A (QDR 4500) Fan Beam X-ray densitometer for in vivo assessment
of body fat content in mice. METHODS: Precision of DXA fat measurement was
assessed by repeated in vivo scanning and re-positioning of different sized mice
(17.6, 24.6, 34.2 g). DXA fat and total mass measurements were correlated with
dissected tissue weights in 240 female adult mice of seven strains (mean weights
21.9-26.8 g). Accuracy of DXA fat tissue measurements was assessed by chemical
analysis in a subgroup of 40 female decapitated mice (mean weights 19.6-28.4 g).
RESULTS: Precision of the DXA measurements for fat mass was dependent on body
weight (mean coefficient of variation, CV, 34.2 g mouse: 7.53 +/- 0.13%; 24.6 g
mouse: 32.16 +/- 0.17%; 17.6 g mouse: 40.64 +/- 0.06%). A moderate to high
correlation with the dissected fat tissue weights was found for all seven
strains: r = 0.52, p <= 0.01 (AJ) to r = 0.83, p <= 0.01 (CBA, both mean weight =
22 g). The correlation of DXA measurements with the chemical analysis of the
carcass was good to excellent (r = 0.80, p <= 0.01). CONCLUSION: The results
demonstrate that the QDR 4500A DXA can be utilised for in vivo measurements of
fat content in mice weighing as little as 20 g, with excellent correlations
between tissue dissections and chemical analysis demonstrating high consistency
of the measurements. DXA values were consistently slightly lower than those by
direct chemical analysis; however, the limits of agreement (mean difference 0.96
g) demonstrated good concordance between the two methods.
PMID- 24351434
TI - Gelsolin levels are decreased in ankylosing spondylitis patients undergoing anti
TNF-alpha therapy.
AB - OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients
with ankylosing spondylitis (AS) undergoing TNF-alpha antagonist-infliximab
therapy are altered compared with controls and to establish whether disease
activity, systemic inflammation and metabolic syndrome are potential determinants
of circulating GSN levels in these patients. METHODS: We assessed GSN serum
concentrations in a series of 30 non-diabetic AS patients without cardiovascular
(CV) disease undergoing TNF-alpha antagonist-infliximab therapy and 48 matched
controls. GSN levels were measured immediately before and after an infliximab
infusion. Correlations of GSN serum levels with disease activity, systemic
inflammation and metabolic syndrome were assessed. Potential changes in GSN
concentration following an infusion of anti-TNF-alpha monoclonal antibody
infliximab were also analysed. RESULTS: Although at the time of the study AS
patients undergoing anti-TNF-alpha therapy had adequate control of the disease
(mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls
(mean+/-SD: 38660.42+/-23624.6 ng/ml versus 68975.43+/-31246.79 ng/ml; p<0.0001).
When AS patients were stratified according to sex, we observed that GSN levels
were significantly lower in men than in women (p=0.032). However, no differences
in GSN levels according to the specific clinical features of the disease were
seen. No association was found between GSN concentration and adipokines or
biomarkers of endothelial cell activation. However, correlation between basal GSN
levels and insulin resistance was observed. A single infliximab infusion did not
lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is
reduced in AS patients undergoing periodical anti-TNF-alpha therapy and low
disease activity. Potential association with some metabolic syndrome features
seems to exist.
PMID- 24351435
TI - Photochromic charge transfer processes in natural pink and brown diamonds.
AB - Natural pink and brown diamonds exhibit surprising photochromic phenomena when
optically pumped with ultraviolet light of photon energy epsilon >= 4.1 eV,
including a subsequent sensitivity to infrared pumps, which is not evident prior
to UV exposure. In this study, we observe the dependence of photochromism on pump
photon energy and intensity, for both UV and IR pumps. From these observations,
we propose a model of several distinct charge transfer processes between multiple
species of optically active defect centres. We show it is likely that the UV
induced behaviour of pink diamond photochromism is linked to the vacancy clusters
responsible for brown colouration in diamonds.
PMID- 24351436
TI - Response to comment on letter for: 'Prevalence of brain magnetic resonance
imaging meeting Barkhof and McDonald criteria for dissemination in space among
headache patients'.
PMID- 24351438
TI - 1 November 2012 - 31 October 2013.
PMID- 24351437
TI - Comment on: 'Prevalence of brain magnetic resonance imaging meeting Barkhof and
McDonald criteria for dissemination in space among headache patients'.
PMID- 24351439
TI - Influence of transfemoral amputation length on resulting loads at the
osseointegrated prosthesis fixation during walking and falling.
AB - BACKGROUND: Transfemoral amputation is a surgical measure in which the surgeon
typically conserves as much tissue and bone as possible. Osseointegrated fixation
of prostheses is a promising alternative to conventional socket-based fixation.
However, osseointegrated prostheses pose some risk of possible bone fracture
under unexpected high-impact loading scenarios, such as a fall, and this should
be protected against by a safety element. The aim of the present study was to
determine the effect of amputation height on the forces and moments at the bone
prosthesis interface during normal gait and three falling scenarios. METHODS:
Forces and moments at four amputation heights were determined from a multi-body
simulation driven by data captured from an able-bodied participant. FINDINGS: In
all three falling scenarios, forces were relatively independent of amputation
height, while moments generally displayed considerable increases with shorter
residual limb length. Peak moments ranged from 105Nm (SD 75) (most distal
amputation height) to 229Nm (SD 99) (most proximal amputation height) for a
"falling during gait" scenario. INTERPRETATION: Our findings reveal the
dependence of interface loads on amputation height in normal gait and falling.
This information may lead to improved prosthesis safety elements against bending
moments.
PMID- 24351441
TI - Route of hysterectomy: an evidence-based approach.
AB - The number of hysterectomies performed has long been a concern; now the
appropriateness of the surgical method is under more careful scrutiny. What is
the clinically appropriate route and method for hysterectomy in a given patient?
To ensure that each patient receives the best possible care at reasonable costs,
physicians must closely examine recent data comparing surgical approaches to
hysterectomy. So, what is the most evidence-based approach for hysterectomy?
PMID- 24351442
TI - Ethical dimensions of first-trimester fetal aneuploidy screening.
AB - Noninvasive first-trimester fetal aneuploidy screening provides pregnant women
with risk assessment information early in pregnancy. Noninvasive first-trimester
aneuploidy screening includes imaging of the fetus and maternal serum analyte and
assessment of fetal genetic material in the maternal circulation. The ethical
challenges of noninvasive first-trimester fetal aneuploidy screening concern the
physician's role in the informed consent process for risk assessment, the goal of
which is to empower pregnant women to make informed decisions about noninvasive
aneuploidy screening. This article provides physicians with an ethical framework
for the professionally responsible management of these ethical challenges and for
those related to emerging technologies.
PMID- 24351440
TI - MicroRNA expression signatures of stage, grade, and progression in clear cell
RCC.
AB - Clear cell RCC is the most common, and more likely to metastasize, of the three
main histological types of RCC. Pathologic stage is the most important prognostic
indicator and nuclear grade can predict outcome within stages of localized RCC.
Epithelial tumors are thought to accumulate a series of genetic and epigenetic
changes as they progress through well-defined clinical and histopathological
changes. MicroRNAs (miRNAs) are involved in the regulation of mRNA expression
from many human genes and miRNA expression is dysregulated in cancer. To better
understand the contribution of dysregulated miRNA expression to the progression
and biology of ccRCC, we examined the differences in expression levels of 723
human miRNAs through a series of analyses by stage, grade, and disease
progression status in a large series of 94 ccRCC. We found a consistent signature
that included significant upregulation of miR-21-5p, 142-3p, let-7g-5p, let-7i-5p
and 424-5p, as well as downregulation of miR-204-5p, to be associated with ccRCC
of high stage, or high grade, or progression. Discrete signatures associated with
each of stage, grade, or progression were also identified. The let-7 family was
significantly downregulated in ccRCC compared with normal renal parenchyma.
Expression of the 6 most significantly differentially expressed miRNAs between
ccRCC was verified by stem-loop qRT-PCR. Pathways predicted as targets of the
most significantly dysregulated miRNAs included signaling, epithelial cancers,
metabolism, and epithelial to mesenchymal transition. Our studies help to further
elucidate the biology underlying the progression of ccRCC and identify miRNAs for
potential translational application.
PMID- 24351443
TI - Noninvasive prenatal detection of aneuploidy.
AB - Noninvasive prenatal testing (NIPT) uses cell-free fetal DNA from the plasma of
pregnant women to provide valuable information about the potential risks for
fetal aneuploidy. This article provides a historical overview of both invasive
diagnostic testing and serum screening approaches, both biochemical and the newer
molecular noninvasive prenatal testing assays, used to identify patients who
would be best served by invasive testing.
PMID- 24351444
TI - Scleral buckling surgery and eye pain: assessment of chronic eye pain during the
postoperative period of scleral buckling surgery.
AB - PURPOSE: To assess the progression of eye pain after scleral buckling surgery to
treat rhegmatogenous retinal detachment and to investigate the occurrence and
characteristics of chronic eye pain. METHODS: This was a longitudinal,
prospective, and observational study. Eye pain was measured according to a
numerical analog scale (range, 0-10) for 6 months after scleral buckling surgery.
The sample was divided into two groups, with or without chronic eye pain, to
perform statistical analyses. For this study, chronic eye pain was defined as
postoperative pain beyond 30 days. The following variables were assessed to
investigate the etiology of chronic eye pain: age, gender, ethnicity, degree of
myopia, visual acuity, intraocular pressure, and degree of scleral indentation.
RESULTS: A total of 100 patients were assessed in this study. One particular
sequence of levels on the pain analog scale, specifically 3-2-1-0-0 (intensity of
eye pain on postoperative Days 1, 14, 30, 60, and 180, respectively), was
identified more frequently during the progression of eye pain in the 180-day
follow-up period. The pain resolved for 72% of patients within 30 days. Chronic
eye pain occurred in 18% of the patients. Scleral indentation was the only
statistically significant variable investigated relative to the etiology of
chronic eye pain (P < 0.05). CONCLUSION: Chronic eye pain correlated
significantly with large scleral indentation. Patients with more intense pain at
the onset of the postoperative period tended to develop chronic eye pain.
PMID- 24351445
TI - Enhanced depth imaging optical coherence tomography of choroidal metastasis.
AB - PURPOSE: To evaluate the imaging features of choroidal metastasis using enhanced
depth imaging optical coherence tomography (EDI-OCT). METHODS: Enhanced depth
imaging optical coherence tomography imaging features of 24 choroidal metastatic
tumors with <2.5 mm of thickness on ultrasonography were retrospectively
evaluated. RESULTS: Of the 24 tumors, 10 (42%) were located at the macula and 14
(58%) between the macula and equator. Tumor was plateau-shaped in 18 (75%) tumors
and dome-shaped in 6 (25%) tumors. On EDI-OCT, choroidal metastasis showed low
internal optical reflectivity in 17 (71%) tumors and high internal reflectivity
in 7 (29%) tumors. Most common associated features were overlying
choriocapillaris thinning in 24 (100%) tumors, shaggy or irregular, elongated
photoreceptors in 18 (75%) tumors, subretinal fluid with high-reflective speckles
in 16 (67%) tumors, and thickening of retinal pigment epithelium in 9 (37%)
tumors. The mean tumor thickness was 854 MUm (range, 287-1500 MUm) on EDI-OCT and
2064 MUm (range, 0-2400 MUm) on ultrasonography. After treatment, the mean
decrease in tumor thickness was 520 MUm (range, 134-917 MUm) on EDI-OCT and 714
MUm (range, 0-1500 MUm) on ultrasonography. Internal optical reflectivity changed
from low to high in five tumors. Choriocapillaris thinning and shaggy
photoreceptors improved in four and five tumors, respectively. Subretinal fluid
resolved in four tumors. CONCLUSION: On EDI-OCT, choroidal metastasis showed
overlying choriocapillaris thinning, plateau-shaped tumor, shaggy photoreceptors,
and subretinal fluid with high-reflective speckles in more than half of the
tumors. Enhanced depth imaging optical coherence tomography was more sensitive
than ultrasonography in the evaluation of small metastatic tumors at presentation
and after treatment.
PMID- 24351446
TI - First symptoms and their age of onset in macular telangiectasia type 2.
AB - PURPOSE: To investigate the first symptoms and their age of onset in a large
cohort of patients with macular telangiectasia type 2. METHODS: Patients with the
characteristic findings of macular telangiectasia type 2 were interviewed. Data
collection also included a chart review to determine the delay of the correct
diagnosis and visual function 10 years after the onset of first symptoms.
RESULTS: Of 91 patients, 72 (79%) reported impaired reading ability as their
first symptom, followed by metamorphopsia in 12%. The age of onset was most
frequent (76%) in the sixth or seventh decade of life (50-69 years), and 58% of
the patients were symptomatic before the age of 60 years. The median delay
between first symptoms and the diagnosis of macular telangiectasia type 2 before
the year 2005 was 7 years and has decreased to 1 year thereafter. Ten years after
the onset of first symptoms, distance visual acuity of the better eye was >=20/25
in 35% and <=20/50 in 17%. CONCLUSION: Impaired reading ability was the most
common initial visual disturbance of patients with macular telangiectasia type 2,
starting generally between the age of 50 and 70 years. Knowledge of the
presenting symptoms of macular telangiectasia type 2 together with recently
identified characteristic morphologic alterations on retinal imaging will likely
lead to earlier accurate diagnosis of this disease entity.
PMID- 24351447
TI - Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe
Impairment Battery factor analysis.
AB - INTRODUCTION: The Severe Impairment Battery (SIB) is validated for assessing
cognition in patients with severe dementia. The current analysis aimed to further
investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB
factor scores, in patients with moderately severe-to-severe Alzheimer's disease
(AD). METHODS: This was a retrospective analysis of a 26-week, multicenter,
randomized, double-blind, placebo-controlled study of oral rivastigmine conducted
in Spain. Previously reported outcome measures included the full SIB. Current
analyses examined calculated scores and effect sizes for the change from baseline
at Week 26 on: newly defined SIB subscales (derived by a factor analysis of the
40 SIB items, using the PROC FACTOR function (SAS)); previously defined memory,
language and praxis subscales (derived by previous analysis of the nine SIB
domains); and the individual SIB items. Treatment differences were assessed.
RESULTS: SIB data were provided by 104 rivastigmine-treated patients and 106
patients receiving placebo (Intent-To-Treat Last Observation Carried Forward
population). Significantly less decline was observed on the previously defined
memory and language subscales, and the newly defined working memory/memory
subscale in rivastigmine-treated patients (all P < 0.05 versus placebo).
Calculation of effect sizes demonstrated numerically greater efficacy of
rivastigmine versus placebo on each of the subscales, and a broad range of SIB
items; greatest effect sizes were observed on SIB items assessing the current
month (effect size = 0.30) and digit span series (effect size = 0.33).
CONCLUSIONS: These data suggest the observed efficacy of rivastigmine in
moderately severe-to-severe AD is likely a cumulative effect across a range of
tasks. Rivastigmine demonstrates broad cognitive efficacy in this patient
population.
PMID- 24351448
TI - Correlation between food intake change patterns and body weight loss in middle
aged women in Japan.
AB - The patterns of food intake change which are effective for weight loss have not
been clearly researched yet. The objective of this study was to examine the
correlation between food intake change patterns and body weight loss. One hundred
and two overweight women completed a 2-day dietary record before and after a 12
week weight-reduction program, and 28 food groups were classified. Patterns of
food intake change were derived by cluster analysis, and compared with the
changes of physical measurements and nutrition intake. As a result, decreasing
Japanese foods pattern (DJP), increasing healthy foods pattern (IHP) and changing
staple foods pattern (CSP) were classified. DJP and CSP mainly changed staple
food intake. IHP decreased sugars, oils, beans except soybeans and meat intake,
and increased fruits and seafood intake. DJP decreased fat and carbohydrate
intake most but CSP showed least change. IHP also decreased fat and carbohydrate
intake but maintained protein intake. Although no significant differences were
seen in the change of energy intake between IHP and DJP or CSP, subjects of IHP
showed the largest reduction in mean body weight, BMI, %body fat, waist
circumference and serum triacylglycerol after adjusting for age and baseline
values. Body weight, BMI and %body fat maintained their significance further
adjusting for changes in energy intake and the number of walking steps. Food
intake change patterns affected the magnitude of body weight loss independent of
energy intake. In addition to energy intake, assessment of food intake change
patterns could be useful for effective weight loss.:
PMID- 24351449
TI - Prepro-TRH 178-199 inhibits histamine- or restraint stress-induced activation of
corticotropin releasing hormone production in rat hypothalamus.
AB - Under restraint stress conditions, prepro-thyrotropin releasing hormone (TRH) 178
199 suppresses adrenocorticotropic hormone (ACTH) secretion from the rat
pituitary, which indicates that prepro-TRH 178-199 is a candidate endogenous
corticotropin releasing inhibitory factor (CRIF). Restraint stress also activates
the release of hypothalamic neuronal histamine, which increases both the
expression of CRH mRNA in the paraventricular nucleus (PVN) and plasma
concentrations of ACTH. The aim of this study was to determine whether prepro-TRH
178-199 modulates histamine- or restraint stress-induced activation of
corticotropin releasing hormone (CRH) in the rat hypothalamus. Infusion of prepro
TRH 178-199 into the third cerebroventricle (i3vt) at a dose of 6 MUg/kg
significantly decreased the amount of CRH in the PVN, as compared to vehicle
treated controls (p < 0.05), but did not affect the CRH amount in other
hypothalamic regions. Restraint stress increased the amount of CRH in the PVN and
ventromedial hypothalamic nucleus (VMH), as compared to non-restrained controls
(p < 0.05); this was attenuated by pretreatment with i3vt infusion of prepro-TRH
178-199 (p < 0.05). I3vt infusion of histamine (270 nmol/rat) suppressed
cumulative food consumption over 24 h, increased plasma ACTH concentrations, and
increased the content of CRH in the PVN, as compared to vehicle-treated controls
(p < 0.05 for each); these effects were attenuated by pretreatment with prepro
TRH 178-199 (p < 0.05). These results suggest that prepro-TRH 178-199 may
regulate ACTH secretion by affecting basal and histamine- or stress-induced
synthesis and/or secretion of CRH and ACTH by modulating histaminergic input to
the PVN and VMH.:
PMID- 24351450
TI - The -3826 A -> G variant of the uncoupling protein-1 gene diminishes
thermogenesis during acute cold exposure in healthy children.
AB - SUMMARY: Uncoupling protein-1 (UCP1) activity in brown adipose tissue increases
energy expenditure, and contributes to diet-induced or cold-induced
thermogenesis. We previously reported that children with -3826 A -> G nucleotide
variant of the UCP1 gene had lowered postprandial thermogenesis in response to a
high-fat meal. In this study, we investigated whether the UCP1 polymorphism was
associated with cold-induced thermogenesis in healthy children. Resting energy
expenditure was measured in 19 children (6-10 years) by indirect calorimetry for
30 min under thermoneutral (25 degrees C) or cold conditions (10 degrees C) in
an environmental chamber. The activity of autonomic nervous system (ANS) was
assessed by power spectral analysis of heart rate variability (HRV). Samples of
saliva were collected for cortisol determination at the end of the experimental
session. Each experiment was performed on 2 consecutive days. Children were
genotyped for the UCP1 polymorphism with a PCR-restriction fragment length
analysis using buccal samples. During cold exposure, total power of the HRV, an
index of the overall ANS activity, as well as the salivary cortisol concentration
significantly increased in the children with homozygous (GG) for the UCP1
polymorphism while only cortisol response was found in the carriers of the wild
type (AA) and heterozygous (AG) alleles; however, the GG allele group showed a
lower cold-induced thermogenesis compared to the AA + AG group. In conclusion,
despite cold-induced autonomic stimulation, the GG allele carriers have a reduced
capacity for thermogenesis in response to acute cold exposure, suggesting that
such reduced UCP1-linked thermogenesis may have adverse effects on the regulation
of body weight.:
PMID- 24351451
TI - The influence of physical activity-induced energy expenditure on the variance in
body weight change among individuals during a diet intervention.
AB - SUMMARY: OBJECTIVE: We investigated the relationship between the variability in
body weight change among individuals and diet restriction or physical activity
during a 14-week intervention. DESIGN: A prospective clinical trial with a 14
week weight reduction intervention design. In total, 90 middle aged, Japanese,
obese women enrolled as subjects. MEASUREMENTS: The outcome variable was the
change in body weight during the intervention period. Other primary variables
were total energy intake, carbohydrate intake, fat intake, protein intake, total
energy expenditure (TEE), and activity energy expenditure (AEE). Diet intake was
assessed by 3 days, weighed dietary records and dietary recall interviews.
Physical activity was assessed by a uniaxial accelerometry sensor and a diary of
exercise. RESULTS: Significant reductions were observed in body weight (-8.5 kg)
as a result of intervention. When the subjects were assigned to three categories
depending on AEE during intervention, the loss of body weight was significantly
greater for subjects within the upper (-9.6 kg) AEE category than for those in
the middle (-8.5 kg) or lower AEE (-7.5 kg) categories. In addition, a
significant correlation (r = 0.57, p < 0.0001) was observed between a subject's
AEE before and during the intervention. On the other hand, no significant
correlation was observed between body weight reduction and energy intake,
indicating that strict diet restriction does not always result in a large weight
loss. CONCLUSION: Activity energy expenditure, not only through voluntary
exercise but also through spontaneous, daily, physical activities can have a
positive effect on reducing body weight.
PMID- 24351452
TI - Incidence of beta3-adrenergic receptor polymorphism and prediction of successful
weight reduction with mazindol therapy in severely obese Japanese subjects.
AB - SUMMARY: Mazindol, a centrally acting monoamine re-uptake inhibitor, enhances
satiety and supports body weight loss, but response to this drug among obese
patients is very variable. The possible involvement of the Trp64Arg polymorphism
of the beta3-adrenergic receptor (ADRB3) gene in the development of severe
obesity and weight loss response to anorexigenic drugs has not been established.
In the present study, the allelic frequency of the Trp64Arg ADRB3 gene
polymorphism was determined in massively obese Japanese outpatients (BMI > 35
kg/m(2)), and we investigated whether allelic differences may determine the
weight loss effect of mazindol. The allelic frequency of Trp64Arg heterozygotes
and homozygotes did not differ in severely obese subjects compared to non-obese
subjects. Trp64Arg heterozygotes experienced significantly increased weight loss
and reduced blood pressure following mazindol administration for 12 weeks. Thus
the ADRB3 gene polymorphism is predictive for difficulty in weight reduction with
mazindol treatment, but is not related to the development of severe obesity in
the Japanese population.:
PMID- 24351453
TI - Family history of coronary heart disease is associated with a higher incidence of
nonalcoholic fatty liver disease: Central obesity the likely link.
AB - SUMMARY: AIM: To examine the relationship between family history of coronary
heart disease (CHD), hypertension, and diabetes with risk of non-alcoholic fatty
liver disease (NAFLD), and the possible interaction between these family
histories and metabolic components for NAFLD. METHODS: The 202 health office
workers with no evidence of excessive alcohol drinking or hepatitis B or C virus
infection were enrolled in the present study performed from March to June 2004.
RESULTS: NAFLD was identified in 68 subjects by abdominal ultrasound. Logistic
regression analysis showed that the presence of CHD family history increased the
risk of NAFLD by 2.25-fold, 95% CI 1.1-4.1 (P = 0.014), while family history of
diabetes or hypertension did not increase the risk. In combination with the
presence of a family history of CHD, the effect on odds ratios (ORs) was
increased for several metabolic features in predicting the incidence of NAFLD,
including increased waist circumference, hypertriglyceridemia, hypertension and
the occurrence of the metabolic syndrome. In a logistic regression model, the CHD
family history enhances the summary predictive power of baseline clinical
variables for NAFLD, but when the occurrence of increased waist circumference and
hypertriglyceridemia are considered, the predictive value of a family history of
CHD is no longer significant. CONCLUSION: This study has shown that the CHD
family history may be clinically useful and associated with the occurrence of
NAFLD, and that the likely link is through central obesity and the metabolic
syndrome.
PMID- 24351454
TI - Effective prevention of metabolic syndrome: A motto for healthy habits-"none of
one, less of two, more of three".
AB - SUMMARY: OBJECTIVE: To demonstrate the correlation of six healthy habits with
metabolic syndrome. METHODS: Our mnemonic or motto for promoting healthy habits
is "none of one, less of two, more of three". The "one" behavior is smoking. The
"two" things are intake of food and alcohol. The "three" things are exercise,
rest and enjoyable activities. In 2005, the diagnostic criterion for Japan
specific metabolic syndrome was published. DESIGN: Cross-sectional study of
preventing metabolic syndrome by practicing these six healthy habits. SUBJECTS:
18,139 Japanese who visited the Health Science Center at Jikei University
Hospital in Japan for medical check-ups. MEASUREMENTS: Participants completed a
simple, self-administered questionnaire on the lifestyle with these mottos.
Metabolic syndrome was diagnosed with the above criterion. RESULTS: The mean
number of practicing six healthy habits was 3.4 +/- 1.3 in the subjects with
metabolic syndrome, which was significantly lower than that (3.7 +/- 1.3) in the
subjects without metabolic syndrome. The prevalence of metabolic decreased
significantly in relation to the number of healthy habits practiced (20.9% for
none, 17.4% for one, 15.0% for two, 13.1% for three, 10.5% for four, 8.4% for
five, and 7.2% for six) (p < 0.001). CONCLUSION: Practicing these six healthy
habits may be useful in the prevention of metabolic syndrome.
PMID- 24351455
TI - Metabolic dysfunction in anorexia nervosa.
AB - SUMMARY: CONTEXT: Anorexia nervosa (AN) is an eating disorder characterized by
self-induced energy deficit and low body weight with major consequences for most
organ systems and a tendency towards self-perpetuation. OBJECTIVES: To compare
metabolic responses to glucose and exercise in women hospitalized with AN (n =
10) before and after 6-weeks weight gain program and in lean healthy weight women
(BMI < 22 kg/m(2)) (n = 7). MAIN OUTCOMES: Weight, body composition, indirect
calorimetry, and response of serum insulin, glucose, adiponectin and leptin to
oral glucose (75 g) and to 30-min of cycling at 50 rpm. RESULTS: Patients with AN
had similar lean mass to controls, but had significantly less body fat.
Adiponectin was 43% higher (p < 0.01) and leptin 47% lower in AN subjects versus
controls (p = 0.04). In response to moderate exercise, fasting glucose increased
in AN (p < 0.05), but was unchanged in controls. After glucose ingestion, a trend
towards a greater increase in diet-induced thermogenesis was also observed in
patients with AN (p = 0.07). Despite a further 6 weeks as in patients, weight was
not significantly changed in AN. Similarly, glucose, insulin, leptin or
adiponectin were not altered. CONCLUSIONS: AN patients appear metabolically
healthy under resting conditions, but their responses to physiological stressors
differed from those of controls. Potential impediments to weight gain should be
further investigated to define mechanisms with a view to improving the
effectiveness of nutritional management.
PMID- 24351456
TI - Obesity and hypertension interact to increase risk of renal cell carcinoma in
Iowa, USA.
AB - SUMMARY: Renal cell carcinoma (RCC) rates in the US have risen, along with those
of obesity and hypertension. We investigated the interactive relationship with
obesity and hypertension (HT) through a population-based case-control study of
RCC in Iowa consisting of 406 cases and 2434 controls. Data on height and weight
at various ages and history of HT were collected and interaction tested by log
likelihood ratio tests. After adjustment, both obesity and HT were independently
and interactively associated with increased RCC risk. Hypertensive subjects,
obese (BMI >= 30) at age 40 were 4.2 (CI: 2.38-6.53) times more likely to develop
RCC as normotensive individuals of normal weight (BMI < 25). A similar
interactive pattern was observed for obesity at age 60 (p = 0.02). Interaction
with obesity was more evident in women (pinteraction = 0.04 age 40, pinteraction
= 0.01 age 60). Our findings suggest that maintaining body weight and/or
controlling HT are strategies for preventing RCC.:
PMID- 24351457
TI - Applicability of the linear-quadratic model to single and fractionated
radiotherapy schedules: an experimental study.
AB - The aim of this study was to examine the applicability of the linear-quadratic
(LQ) model to single and fractionated irradiation in EMT6 cells. First, the
alpha/beta ratio of the cells was determined from single-dose experiments, and a
biologically effective dose (BED) for 20 Gy in 10 fractions (fr) was calculated.
Fractional doses yielding the same BED were calculated for 1-, 2-, 3-, 4-, 5-, 7
, 15- and 20-fraction irradiation using LQ formalism, and then irradiation with
these schedules was actually given. Cell survival was determined by a standard
colony assay. Differences in cell survival between pairs of groups were compared
by t-test. The alpha/beta ratio of the cells was 3.18 Gy, and 20 Gy in 10 fr
corresponded to a BED3.18 of 32.6 Gy. The effects of 7-, 15- and 20-fraction
irradiation with a BED3.18 of 32.6 Gy were similar to those of the 10-fraction
irradiation, while the effects of 1- to 5-fraction irradiation were lower. In
this cell line, the LQ model was considered applicable to 7- to 20-fraction
irradiation or doses per fraction of 2.57 Gy or smaller. The LQ model might be
applicable in the dose range below the alpha/beta ratio.
PMID- 24351458
TI - Analysis of prognostic factors in localized high-risk prostate cancer patients
treated with HDR brachytherapy, hypofractionated 3D-CRT and neoadjuvant/adjuvant
androgen deprivation therapy (trimodality therapy).
AB - Trimodality therapy consisting of high dose rate (HDR) brachytherapy combined
with external beam radiation therapy (EBRT), neoadjuvant hormonal therapy (NHT)
and adjuvant hormonal therapy (AHT) has been used to treat localized high-risk
prostate cancer. In this study, an analysis of patients receiving the trimodality
therapy was performed to identify prognostic factors of biochemical relapse-free
survival (bRFS). Between May 2005 and November 2008, 123 high-risk prostate
cancer patients (D'Amico classification) were treated with NHT prior to HDR
brachytherapy combined with hypofractionated EBRT. Among these patients, 121 had
completed AHT. The patients were assigned by time to be treated with a low-dose
or high-dose arm of HDR brachytherapy with subsequent hypofractionated 3D
conformal radiation therapy (3D-CRT). Multivariate analysis was used to determine
prognostic factors for bRFS. With a median follow-up of 60 months, the 5-year
bRFS for all patients was 84.3% (high-dose arm, 92.9%; low-dose arm, 72.4%, P =
0.047). bRFS in the pre-HDR PSA <= 0.1 ng/ml subgroup was significantly improved
compared with that in the pre-HDR PSA > 0.1 ng/ml subgroup (88.3% vs 68.2%, P =
0.034). On multivariate analysis, dose of HDR (P = 0.045, HR = 0.25, 95% CI =
0.038-0.97) and pre-HDR PSA level (P = 0.02 HR = 3.2, 95% CI = 1.18-10.16) were
significant prognostic factors predicting bRFS. In high-risk prostate cancer
patients treated with the trimodality therapy, the dose of HDR and pre-HDR PSA
were significant prognostic factors. The pre-HDR PSA <= 0.1 subgroup had
significantly improved bRFS. Further studies are needed to confirm the relevance
of pre-HDR PSA in trimodality therapy.
PMID- 24351459
TI - Simulational study of a dosimetric comparison between a Gamma Knife treatment
plan and an intensity-modulated radiotherapy plan for skull base tumors.
AB - Fractionated stereotactic radiotherapy (SRT) is performed with a linear
accelerator-based system such as Novalis. Recently, Gamma Knife Perfexion (PFX)
featured the Extend system with relocatable fixation devices available for SRT.
In this study, the dosimetric results of these two modalities were compared from
the viewpoint of conformity, heterogeneity and gradient in target covering. A
total of 14 patients with skull base tumors were treated with Novalis intensity
modulated (IM)-SRT. Treatment was planned on an iPlan workstation. Five- to seven
beam IM-SRT was performed in 14-18 fractions with a fraction dose of 2.5 or 3 Gy.
With these patients' data, additional treatment planning was simulated using a
GammaPlan workstation for PFX-SRT. Reference CT images with planning structure
contour sets on iPlan, including the planning target volume (PTV, 1.1-102.2 ml)
and organs at risk, were exported to GammaPlan in DICOM-RT format. Dosimetric
results for Novalis IM-SRT and PFX-SRT were evaluated in the same prescription
doses. The isocenter number of PFX was between 12 and 50 at the isodose contour
of 50-60%. The PTV coverage was 95-99% for Novalis and 94-98% for PFX. The
conformity index (CI) was 1.11-1.61 and 1.04-1.15, the homogeneity index (HI) was
1.1-3.62 and 2.3-3.25, and the gradient index (GI) was 3.72-7.97 and 2.54-3.39
for Novalis and PFX, respectively. PTV coverage by Novalis and PFX was almost
equivalent. PFX was superior in CI and GI, and Novalis was better in HI. Better
conformality would be achieved by PFX, when the homogeneity inside tumors is less
important.
PMID- 24351461
TI - Vulnerable children: creating a service fit for purpose.
PMID- 24351462
TI - Embedding social inclusion in general practice: time for action.
PMID- 24351463
TI - Why our farming patients are at an increased risk of taking their own lives this
year.
PMID- 24351464
TI - Medically unexplained symptoms: evidence, guidelines, and beyond.
PMID- 24351465
TI - LABA monotherapy in asthma: an avoidable problem.
PMID- 24351466
TI - Proceed with caution.
PMID- 24351467
TI - The right to die peacefully.
PMID- 24351469
TI - Out-of-hours care.
PMID- 24351470
TI - An additional cause of prescribing error.
PMID- 24351471
TI - Response to 'Do the elderly have a voice'.
PMID- 24351472
TI - Non-directed altruistic kidney donation.
PMID- 24351473
TI - The postcode lottery of GP training: Time Out of Programme.
PMID- 24351474
TI - CSA pass rates.
PMID- 24351475
TI - Sustainability, carbon footprints, and dyspepsia.
PMID- 24351476
TI - Cardiovascular safety of non-steroidal anti-inflammatory drugs.
PMID- 24351477
TI - Diagnosing somatisation in adults in the first consultation.
PMID- 24351478
TI - Viewpoint: TIA: view from the patient's chair.
PMID- 24351481
TI - The art in general practice.
PMID- 24351479
TI - Chronic fatigue syndrome: a patient's perspective.
PMID- 24351482
TI - 'Stitched drawings' and caring for our older people.
PMID- 24351484
TI - An A-Z of medical philosophy.
PMID- 24351485
TI - Meditation as medication: are attitudes changing?
PMID- 24351486
TI - Viewpoint: Compassion in primary health care: conflicts, politics, and
opportunities.
PMID- 24351490
TI - Curses! Foiled again!!
PMID- 24351491
TI - The challenge of providing medical care to homeless men.
PMID- 24351492
TI - The need for FASTER CARE in the diagnosis of illness in people with intellectual
disabilities.
PMID- 24351493
TI - Lumps, bumps and diagnostic stumps.
PMID- 24351494
TI - Tips for GP trainees working in plastic surgery.
PMID- 24351495
TI - Effect of shared care on blood pressure in patients with chronic kidney disease:
a cluster randomised controlled trial.
AB - BACKGROUND: Chronic kidney disease (CKD) is highly prevalent in patients with
diabetes or hypertension in primary care. A shared care model could improve
quality of care in these patients AIM: To assess the effect of a shared care
model in managing patients with CKD who also have diabetes or hypertension.
Design and setting A cluster randomised controlled trial in nine general
practices in The Netherlands. METHOD: Five practices were allocated to the shared
care model and four practices to usual care for 1 year. Primary outcome was the
achievement of blood pressure targets (130/80 mmHg) and lowering of blood
pressure in patients with diabetes mellitus or hypertension and an estimated
glomerular filtration rate (eGFR)<60 ml/min/1.73 m(2). RESULTS: Data of 90
intervention and 74 control patients could be analysed. Blood pressure in the
intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = -1.0
to 3.2) compared to -0.2 (95% CI = -3.8 to 3.3)/-0.5 (95% CI = -2.9 to 1.8) in
the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and
vitamin D was higher in the intervention group than in the control group (73%
versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P =
0.01, and P = 0.002]). CONCLUSION: A shared care model between GP, nurse
practitioner and nephrologist is beneficial in reducing systolic blood pressure
in patients with CKD in primary care.
PMID- 24351496
TI - Are alarm symptoms predictive of cancer survival?: population-based cohort study.
AB - BACKGROUND: Alarm symptom presentations are predictive of cancer diagnosis but
may also be associated with cancer survival. AIM: To evaluate diagnostic time
intervals, and consultation patterns after presentation with alarm symptoms, and
their association with cancer diagnosis and survival. DESIGN AND SETTING: Cohort
study using the Clinical Practice Research Database, with linked Cancer Registry
data, in 158 general practices. METHOD: Participants included those with
haematuria, haemoptysis, dysphagia, and rectal bleeding or urinary tract cancer,
lung cancer, gastro-oesophageal cancer, and colorectal cancer. RESULTS: The
median (interquartile range) interval in days from first symptom presentation to
the corresponding cancer diagnosis was: haematuria and urinary tract cancer, 59
(28-109); haemoptysis and lung cancer, 35 (18-89); dysphagia and gastro
oesophageal cancer, 25 (12-48); rectal bleeding and colorectal cancer, 49 (20
157). Three or more alarm symptom consultations were associated with increased
odds of diagnosis of urinary tract cancer (odds ratio [OR] 1.84, 95% CI = 1.50 to
2.27), lung cancer (OR = 1.76, 95% CI = 1.07 to 2.90) and gastro-oesophageal
cancer (OR = 2.17, 95% CI = 1.48 to 3.19). Longer diagnostic intervals were
associated with increased mortality only for urinary tract cancer (hazard ratio
2.23, 95% CI = 1.35 to 3.69). Patients with no preceding alarm symptom had
shorter survival from diagnosis of urinary tract, lung or colorectal cancer than
those presenting with a relevant alarm symptom. CONCLUSION: After alarm symptom
presentation, repeat consultations are associated with cancer diagnoses. Longer
diagnostic intervals appeared to be associated with a worse prognosis for urinary
tract cancer only. Mortality is higher when cancer is diagnosed in the absence of
alarm symptoms.
PMID- 24351497
TI - Reducing inappropriate accident and emergency department attendances: a
systematic review of primary care service interventions.
AB - BACKGROUND: Inappropriate attendances may account for up to 40% of presentations
at accident and emergency (A&E) departments. There is considerable interest from
health practitioners and policymakers in interventions to reduce this burden.
AIM: To review the evidence on primary care service interventions to reduce
inappropriate A&E attendances. DESIGN AND SETTING: Systematic review of UK and
international primary care interventions. METHOD: Studies published in English
between 1 January 1986 and 23 August 2011 were identified from PubMed, the NHS
Economic Evaluation Database, the Cochrane Collaboration, and Health Technology
Assessment databases. The outcome measures were A&E attendances, patient
satisfaction, clinical outcome, and intervention cost. Two authors reviewed
titles and abstracts of retrieved results, with adjudication of disagreements
conducted by the third. Studies were quality assessed using the Scottish
Intercollegiate Guidelines Network checklist system where applicable. RESULTS: In
total, 9916 manuscripts were identified, of which 34 were reviewed. Telephone
triage was the single best-evaluated intervention. This resulted in negligible
impact on A&E attendance, but exhibited acceptable patient satisfaction and
clinical safety; cost effectiveness was uncertain. The limited available evidence
suggests that emergency nurse practitioners in community settings and community
health centres may reduce A&E attendance. For all other interventions considered
in this review (walk-in centres, minor injuries units, and out-of-hours general
practice), the effects on A&E attendance, patient outcomes, and cost were
inconclusive. CONCLUSION: Studies showed a negligible effect on A&E attendance
for all interventions; data on patient outcomes and cost-effectiveness are
limited. There is an urgent need to examine all aspects of primary care service
interventions that aim to reduce inappropriate A&E attendance.
PMID- 24351498
TI - GPs prescribing of strong opioid drugs for patients with chronic non-cancer pain:
a qualitative study.
AB - BACKGROUND: Chronic non-cancer pain (CNCP) is common in the UK. GPs manage most
patients with such pain. Previous research has suggested that prescribing is
influenced by patient and doctor factors, but less is known about the decision-
making process involved in prescribing opioid drugs for CNCP. AIM: To describe
the factors influencing GPs' prescribing of strong opioid drugs for CNCP. Design
and setting Semi-structured interviews and a focus group of a purposive sample of
GPs from a range of practice settings including male and female GPs with
experience of prescribing strong opioids. METHOD: Transcripts of interviews and a
focus group were analysed using qualitative research methodology (thematic
analysis). RESULTS: GPs described prescribing opioid drugs for patients with CNCP
as being different from treating cancer related pain. GPs followed accepted
stepwise approaches in their prescribing for CNCP. They reported difficulty in
assessing the level of pain and concern over duration of use of strong opioids
and their possible side effects, tolerance, and addiction. Variation in reported
practice was observed, which may be linked to experience and significant events.
CONCLUSION: GPs in this study demonstrated a thoughtful attitude towards
prescribing strong opioids for CNCP. They were aware of the difficulties of long
term strong opioid prescription. Only a few GPs had had specific training in
chronic pain management and this may explain some of the variation in practice
reported. GPs may benefit from training in pain assessment and long-term
management of patients with CNCP.
PMID- 24351500
TI - Can antiviral treatment for hepatitis C be safely and effectively delivered in
primary care?: a narrative systematic review of the evidence base.
AB - BACKGROUND: The burden of hepatitis C (HCV) treatment is growing, as is the
political resolve to tackle the epidemic. Primary care will need to work more
closely with secondary care to succeed in reducing the prevalence of chronic HCV.
AIM: To identify research relating to the provision of antiviral treatment for
HCV in primary care. DESIGN AND SETTING: A narrative systematic review of six
databases. Method Medline, Embase, Cinahl, PsycINFO, Web of Science, and Cochrane
were searched. Relevant journals were searched by hand for articles to be
included in the review. Reference lists of relevant papers were reviewed and full
text papers were retrieved for those deemed to potentially fulfil the inclusion
criteria of the review. RESULTS: A total of 683 abstracts led to 77 full-text
articles being retrieved, of which 16 were finally included in the review. An
evidence base emerged, highlighting that community-based antiviral treatment
provision is feasible and can result in clinical outcomes comparable to those
achieved in hospital outpatient settings. Such provision can be in mainstream
general practice, at community addiction centres, or in prisons. GPs must be
trained before offering such a service and there is also a need for ongoing
specialist supervision of primary care practice. Such training and supervision
can be delivered by teleconference, although, even with such ready availability
of training and supervision, only a minority of GPs are likely to want to provide
antiviral treatment. CONCLUSION: There is emerging evidence supporting the
effectiveness of antiviral treatment provision for patients with chronic
hepatitis C in a wide variety of primary care and wider community settings.
Training and ongoing supervision of primary care practitioners by specialists is
a prerequisite. There is an opportunity through future research activity to
evaluate typologies of patients who would be best served by primary care-based
treatment and those for whom hospital-based outpatient treatment would be most
appropriate.
PMID- 24351499
TI - Patients' experiences of chronic non-malignant musculoskeletal pain: a
qualitative systematic review.
AB - BACKGROUND: Musculoskeletal (MSK) pain is one of the most predominant types of
pain and accounts for a large portion of the primary care workload. AIM: To
systematically review and integrate the findings of qualitative research to
increase understanding of patients' experiences of chronic non-malignant MSK
pain. DESIGN AND SETTING: Synthesis of qualitative research using meta
ethnography using six electronic databases up until February 2012 (Medline,
Embase, Cinahl, Psychinfo, Amed and HMIC). METHOD: Databases were searched from
their inception until February 2012, supplemented by hand-searching contents
lists of specific journals for 2001-2011 and citation tracking. Full published
reports of qualitative studies exploring adults' own experience of chronic non
malignant MSK pain were eligible for inclusion. RESULTS: Out of 24 992 titles,
676 abstracts, and 321 full texts were screened, 77 papers reporting 60
individual studies were included. A new concept of pain as an adversarial
struggle emerged. This adversarial struggle was to: 1) affirm self; 2)
reconstruct self in time; 3) construct an explanation for suffering; 4) negotiate
the healthcare system; and 5) prove legitimacy. However, despite this struggle
there is also a sense for some patients of 6) moving forward alongside pain.
CONCLUSIONS: This review provides a theoretical underpinning for improving
patient experience and facilitating a therapeutic collaborative partnership. A
conceptual model is presented, which offers opportunities for improvement by
involving patients, showing them their pain is understood, and forming the basis
to help patients move forward alongside their pain.
PMID- 24351501
TI - Prevalence of treatment-resistant depression in primary care: cross-sectional
data.
AB - BACKGROUND: Antidepressants are often the first-line treatment for depression in
primary care. However, not all patients respond to medication after an adequate
dose and duration of treatment. Currently, there are no estimates of the
prevalence of treatment-resistant depression (TRD) from UK primary care. AIM: To
estimate the prevalence of TRD in UK primary care. Design and setting Data were
collected as part of a multicentre randomised controlled trial, from 73 general
practices in UK primary care. METHOD: Potential participants (aged 18-75 years
who had received repeated prescriptions for antidepressants) were identified from
general practice records. Those who agreed to be contacted were mailed a
questionnaire that included questions on depressive symptoms (Beck Depression
Inventory [BDI-II]), and adherence to antidepressants. Those who scored >=14 on
the BDI-II and had taken antidepressants for at least 6 weeks at an adequate dose
were defined as treatment resistant. RESULTS: A total of 2439 patients completed
the questionnaire (84% of those who agreed to be contacted), of whom 2129 had
been prescribed an adequate dose of antidepressants for at least 6 weeks. Seventy
seven per cent (95% CI = 75% to 79%) had a BDI score of >=14. Fifty-five per cent
(95% CI = 53% to 58%) (n = 1177) met the study's definition of TRD, of whom 67%
had taken their antidepressants for more than 12 months. CONCLUSION: The high
prevalence of TRD is an important challenge facing clinicians in UK primary care.
A more proactive approach to managing this patient population is required to
improve outcome.
PMID- 24351502
TI - Tips for GP trainees interested in medical education.
PMID- 24351503
TI - A childhood case of eosinophilic gastritis and protein-losing enteropathy.
PMID- 24351504
TI - Pediatric shopping-cart-related injuries treated in US emergency departments,
1990-2011.
AB - This study investigates the effect of the 2004 US shopping cart safety standard
on shopping-cart-related injuries among children younger than 15 years of age by
retrospectively analyzing data from the National Electronic Injury Surveillance
System. An estimated 530 494 children younger than 15 years were treated in US
emergency departments for shopping-cart-related injuries from 1990 to 2011,
averaging 24 113 children annually. The most commonly injured body region was the
head (78.1%). The annual concussion/closed head injury rate per 10 000 children
increased significantly (P < .001) by 213.3% from 0.64 in 1990 to 2.02 in 2011.
Although a shopping cart safety standard was implemented in the United States in
2004, the overall number and rate of injuries associated with shopping carts have
not decreased. In fact, the number and rate of concussions/closed head injuries
have continued to climb. Increased prevention efforts are needed to address these
injuries among children.
PMID- 24351505
TI - Severe pulmonary hypertension as the initial manifestation of systemic lupus
erythematosus: a case report and review of the literature.
AB - Severe pulmonary arterial hypertension (PAH) is rarely observed as the initial
manifestation of systemic lupus erythematosus (SLE), and the diagnosis is often
delayed. Here we present the case of a 32-year-old woman with severe PAH as the
initial manifestation of SLE, who was successfully treated with mycophenolate
mofetil and cyclosporine. This case offered the opportunity to critically review
the epidemiology data, predictive markers, and pathogenic pathways of SLE
associated PAH (SLE-PAH) in relation to the currently available therapeutic
options and to the main clinical trials of the last 10 years focused on the
treatment of SLE-PAH. Mycophenolate mofetil and cyclosporine - currently used in
the maintenance phase of the disease in certain clinical settings - should be
considered, as an alternative to cyclophosphamide, in future clinical trials
aimed at evaluating the most effective treatment of SLE-PAH at presentation.
PMID- 24351506
TI - The role of hypoxia-inducible factor-1alpha and vascular endothelial growth
factor in late-phase preconditioning with xenon, isoflurane and levosimendan in
rat cardiomyocytes.
AB - OBJECTIVES: The protective effects of late-phase preconditioning can be triggered
by several stimuli. Unfortunately, the transfer from bench to bedside still
represents a challenge, as concomitant medication or diseases influence the
complex signalling pathways involved. In an established model of primary neonatal
rat cardiomyocytes, we analysed the cardioprotective effects of three different
stimulating pharmaceuticals of clinical relevance. The effect of additional beta
blocker treatment was studied as these were previously shown to negatively
influence preconditioning. METHODS: Twenty-four hours prior to hypoxia, cells pre
treated with or without metoprolol (0.55 ug/ml) were preconditioned with
isoflurane, levosimendan or xenon. The influences of these stimuli on hypoxia
inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF)
as well as inducible and endothelial nitric synthase (iNOS/eNOS) and
cyclooxygenase-2 (COX-2) were analysed by polymerase chain reaction and western
blotting. The preconditioning was proved by trypan blue cell counts following 5 h
of hypoxia and confirmed by fluorescence staining. RESULTS: Five hours of hypoxia
reduced cell survival in unpreconditioned control cells to 44 +/- 4%. Surviving
cell count was significantly higher in cells preconditioned either by 2 * 15 min
isoflurane (70 +/- 16%; P = 0.005) or by xenon (59 +/- 8%; P = 0.049). Xenon
preconditioned cells showed a significantly elevated content of VEGF (0.025 +/-
0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 +/- 0.006
IDV in controls; P = 0.0003). The protein expression of HIF-1alpha was increased
both by levosimendan (0.563 +/- 0.175 IDV vs 0.142 +/- 0.042 IDV in controls; P =
0.0289) and by xenon (0.868 +/- 0.222 IDV; P < 0.0001) pretreatment. A
significant elevation of mRNA expression of iNOS was measureable following
preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA
expression was found to be suppressed by beta-blocker treatment for all stimuli.
In our model, independently of the chosen stimulus, beta-blocker treatment had no
significant effect on cell survival. CONCLUSIONS: We found that the stimulation
of late-phase preconditioning involves several distinct pathways that are
variably addressed by the different stimuli. In contrast to isoflurane treatment,
xenon-induced preconditioning does not lead to an increase in COX-2 gene
transcription but to a significant increase in HIF-1alpha and subsequently VEGF.
PMID- 24351507
TI - Is thymectomy in non-thymomatous myasthenia gravis of any benefit?
AB - A best evidence topic in thoracic surgery was written according to a structured
protocol. The question addressed was if thymectomy in non-thymomatous myasthenia
gravis was of any benefit? Overall, 137 papers were found using the reported
search, of which 16 represented the best evidence to answer the clinical
question. The authors, journal, date and country of publication, patient group
studied, study type, relevant outcomes and results of these papers are tabulated.
The outcome variables were similar in all of the papers, including complete
stable remission (CSR), pharmacological remission, age at presentation, gender,
duration of symptoms, preoperative classification (Oosterhius, Osserman or
myasthenia gravis Foundation of America (MGFA)), thymic pathology, preoperative
medications (steroids, immunosuppressants), mortality and morbidity. We conclude
that evidence-based reviews have shown that relative rates of thymectomy patients
compared with non-thymectomy patients attaining outcome indicate that the former
group of patients is more likely to achieve medication-free remission, become
asymptomatic and clinically improve (54%, P < 0.01), particularly patients with
severe and generalized symptoms (P = 0.007). Patients with generalized myasthenia
gravis showed 11% stronger association with favourable outcomes after thymectomy.
Some studies show early remission rates (RRs), as early as 6 months post
thymectomy, of 44%. Overall, the reported remission rate for non-thymomatous
myasthenia gravis is between 38 and 72% up to 10 years of follow-up. Among these
patients, those with thymic hyperplasia show the best complete stable remission
rates (42%, P < 0.04) in the majority of studies. Age showed variability across
the studies and the cut-off was also different among them. Overall age < 45 years
showed a higher probability of achieving complete stable remission during follow
up (81% benefit rate (BR), P < 0.02). Pharmacological improvement is reported
between 6 and 42%. However, the certainty of these benefits has not been
established due to factors such as the confounding differences between myasthenia
gravis patients receiving and not receiving thymectomy, the non-randomized nature
of class II studies and the lack of Class I evidence to support its use. There is
currently a randomized trial ongoing looking at thymectomy by sternotomy vs
controls and the results are eagerly awaited.
PMID- 24351508
TI - No evidence that manual closure of the bronchial stump has a lower failure rate
than mechanical stapler closure following anatomical lung resection.
AB - A best evidence topic in cardiothoracic surgery was written according to a
structured protocol. The question addressed was whether manual closure of the
bronchial stump is safer with lower failure rates than mechanical closure using a
stapling device following anatomical lung resection. One hundred and twenty-nine
papers were identified using the search below. Eight papers presented the best
evidence to answer the clinical question as they included sufficient number of
patients to reach conclusions regarding the issues of interest for this review.
Complications, complication rates and operation time were included in the
assessment. The author, journal, date and country of publication, patient group
studied, study type, relevant outcomes, results and study weaknesses of the
papers are tabulated. When looking at manual vs mechanical staples, it was noted
that stapler failure can occur in around 4% of cases. The rate of bronchopleural
fistula (BPF) development varied more in patients who underwent manual closure
(1.5-12.5%) than in patients who underwent mechanical closure (1-5.7%). Although
most of the studies reviewed showed no statistical differences between manual and
mechanical closure in terms of BPF development, one study, however, showed that
manual closure was significantly associated with lower numbers of postoperative
BPF, while another study showed that mechanical closure is significantly
associated with lower incidence of BPF. When looking at the role of the learning
curve and training opportunities, it seems that the surgeon's inexperience when
using mechanical staples can contribute to BPF development. A surgeon's
experience can play a major role in the prevention of BPF development in patients
having manual closure. Manual closure can provide a cheap and reliable technique
when compared with costs incurred from using staplers, it is applicable in all
situations and can be taught to surgeons in training with an acceptable risk.
However, there is a lack of evidence to suggest that manual closure is better
than mechanical stapler closure following anatomical lung resection.
PMID- 24351510
TI - Mesoscopic features in the transport properties of a Kondo-correlated quantum dot
in a magnetic field.
AB - We study the transport behavior induced by a small bias voltage through a quantum
dot connected to one-channel finite-size wires. We describe the quantum dot using
the Hubbard-Anderson impurity model and we obtain solutions by means of a quantum
Monte Carlo method. We investigate the effect of a magnetic field applied at the
quantum dot in the Kondo regime. We identify mesoscopic oscillations in the
conductance, which are introduced by the magnetic field. This behavior is
analogous to that observed as a function of the temperature.
PMID- 24351511
TI - Persistent back pain in the absence of clear red flags.
AB - A 62-year-old woman with low back pain was eventually diagnosed with vertebral
osteomyelitis after multiple visits to emergency, primary and specialty care. The
absence of traditional 'red flags' from her history and examination serves as an
important reminder that their absence does not necessarily reflect benign
pathology.
PMID- 24351509
TI - Tumour standardized uptake value on positron emission tomography is a novel
predictor of adenocarcinoma in situ for c-Stage IA lung cancer patients with a
part-solid nodule on thin-section computed tomography scan.
AB - OBJECTIVES: Adenocarcinoma in situ (AIS), which is considered to be
pathologically non-invasive in the new International Association for the Study of
Lung Cancer/the American Thoracic Society/the European Respiratory Society
classification, might be present in patients who show a part-solid nodule on thin
section computed tomography (CT) scan. METHODS: Between 2008 and 2011, 556
clinical Stage IA (c-Stage IA) lung cancer patients underwent pulmonary
resection. For all the patients, the findings obtained by preoperative thin
section CT were reviewed and categorized as pure ground-glass nodule (GGN), part
solid nodule or pure-solid nodule based on the findings on thin-section CT, i.e.
based on the consolidation/tumour ratio (CTR). A part-solid nodule was defined as
a tumour with 0 < CTR < 1.0, which indicated focal nodular opacity that contained
both solid and GGN components. All the patients were evaluated by positron
emission tomography (PET), and the maximum standardized uptake value (SUVmax) was
recorded. Several clinicopathological features were investigated to identify
predictors of AIS in clinical Stage IA lung cancer patients with a part-solid
nodule radiologically, using multivariate analyses. RESULTS: One-hundred and
twelve c-Stage IA lung cancer patients showed a part-solid appearance on thin
section CT. Among them, AIS was found in 10 (32%) of the tumours with 0 < CTR <=
0.5, in contrast to 3 (5%) with 0.5 < CTR < 1.0. According to multivariate
analyses, SUVmax and CTR significantly predicted AIS in patients with a part
solid nodule (P = 0.04, 0.02). The mean SUVmax of the patients with AIS was 0.57
(0-1.6). Moreover, in the subgroup of part-solid nodule with a SUVmax of <=1.0
and a CTR of <=0.40, which were calculated as cut-off values for AIS based on the
results for a receiver operating characteristic curve, 6 (40%) patients with
these criteria showed a pathological non-invasive nature, even patients with a
part-solid nodule. CONCLUSIONS: Among c-Stage IA adenocarcinoma with a part-solid
nodule on thin-section CT scan, an extremely low level of SUVmax could reflect a
pure GGN equivalent radiologically and AIS pathologically. The preoperative
tumour SUVmax on PET could yield important information for predicting non
invasiveness in patients with a part-solid nodule.
PMID- 24351512
TI - Post liver transplantation lymphoproliferative disorder mimics recurrence of
hepatocellular carcinoma.
AB - We report a case of Epstein-Barr virus (EBV)-related postliver transplantation
lymphoproliferative disorder (PTLD) in a patient with post liver transplant which
initially presented in a CT scan image mimicking recurrence of hepatocellular
carcinoma. Histopathology showed atypical plasma cell-like infiltration, and
immunohistochemistry confirmed diagnosis of EBV-associated diffuse large B-cell
lymphoma. Typical imaging from dynamic phases contrast CT scan might not
accurately diagnose recurrent HCC in postorthotropic liver transplantation. Liver
biopsy should be performed for accurate diagnosis and proper treatment.
PMID- 24351513
TI - Angiosarcoma of penis.
AB - A 29-year-old male patient presented with proliferative lesion in the glans penis
without any inguinal lymphadenopathy. The biopsy showed a highly vascular
malignant lesion. Subsequent metastasis work-up was negative. Partial amputation
of the penis with close follow-up was performed. Final histopathology was
consistent with angiosarcoma of the penis.
PMID- 24351514
TI - Anisometropic amblyopia in a case of type 2 Waardenburg syndrome.
AB - This study presents a case of an 8-year-old boy with iris heterochromia and
anisometropic amblyopia who was diagnosed with Waardenburg syndrome (WS) type 2.
An ophthalmic examination revealed iris heterochromia and anisometropic amblyopia
in our patient. In the systemic examination, a white forelock and vitiligo on the
arms and body were observed and neurosensory hearing loss was revealed, for which
the patient used hearing aids. Identification and typing of patients with WS is
crucial to address neurosensory hearing loss, glaucoma and fundus changes. While
it might be challenging to communicate with a patient with speech and hearing
problems, visual acuity should be examined carefully and probable amblyopia
should be identified. Anterior segment changes and signs of glaucoma should also
be evaluated in detail.
PMID- 24351515
TI - A teenager with lumbar striae distensae (when a bruise is not a bruise).
AB - A 14-year-old boy was referred to a paediatric clinic after a recent diagnosis of
coeliac disease, which was well controlled on a gluten-free diet. During the
consultation, the mother raised concerns regarding marks that had developed over
her son's back over the past 6 months. On examination, a number of horizontal,
coloured bruise-like marks were noted over the lower back. The appearance was
suspicious of bruising and possible non-accidental injury, although a history of
trauma or injury was denied. Blood tests including a coagulation screen were
arranged which were normal and the patient was followed up twice during a 6-month
period. He remained well but the bruising was persistent. It was concluded that
these were striae associated with pubertal growth. This case summarises the
importance of careful surveillance of bruising in children and illustrates the
association between striae and pubertal growth which may be confused with non
accidental injury.
PMID- 24351517
TI - Prevalence of spondyloarthritis in reference to HLA-B27 in the French population:
results of the GAZEL cohort.
AB - OBJECTIVE: To estimate the prevalence of spondyloarthritis (SpA) in reference to
HLA-B27 in the French population. METHODS: In 1989, 20 625 employees of the
French national gas and electricity company aged 35-50 years were enrolled in the
GAZEL cohort. In 2010, 18 757 still active participants were screened by a
questionnaire validated for the detection of SpA. Responders with available DNA
were retained for further studies. Pelvic radiograph and HLA-B27 typing were
performed in all the self-reported cases of SpA or psoriatic arthritis. Self
reported diagnosis was verified by a qualified rheumatologist. HLA-B27
determination was also performed in subjects without any SpA feature. RESULTS:
The target population consisted of 6556 responders with available DNA. Their
male:female ratio was 3.6 and their mean age was 65.5+/-3.3 years. A diagnosis of
SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27
positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to
0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to
7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17
to 86). CONCLUSIONS: We estimated the prevalence of SpA in the French population
in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in
healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with
HLA-B27 negative subjects.
PMID- 24351516
TI - Sensitivity and sensitisation in relation to pain severity in knee
osteoarthritis: trait or state?
AB - OBJECTIVES: It is not clear whether heightened pain sensitivity in knee
osteoarthritis (OA) is related to sensitisation induced by nociceptive input from
OA pathology ('state') versus other confounding factors. Conversely, some
individuals may be predisposed to sensitisation irrespective of OA ('trait').
METHODS: The Multicenter Osteoarthritis Study is a longitudinal cohort of persons
with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and
comprehensive assessment of factors that can influence pain sensitivity. We
examined the relation of sensitisation and sensitivity assessed by mechanical
temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee
pain severity. To test whether sensitisation and sensitivity is a 'state' induced
by OA pathology, we examined the relation of PPT and TS to knee OA duration and
severity. RESULTS: In 2126 subjects (mean age 68, mean body mass index (BMI) 31,
61% female), PPT and TS were not associated with radiographic OA (ORs 0.9-1.0 for
PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs:
1.7-2.0 for PPT; 1.3-1.6 for TS; p<0.05). Knee OA duration and radiographic
severity were not associated with PPT or TS. CONCLUSIONS: PPT and TS were
associated with OA-related pain, but not radiographic OA after accounting for
pertinent confounders in this large cohort. Lack of association with disease
duration suggests at least some sensitisation and pain sensitivity may be a trait
rather than state. Understanding the relationship between pathological pain and
pain sensitivity/sensitisation offers insight into OA pain risk factors and pain
management opportunities.
PMID- 24351518
TI - Gastrointestinal events in at-risk patients starting non-steroidal anti
inflammatory drugs (NSAIDs) for rheumatic diseases: the EVIDENCE study of
European routine practice.
AB - OBJECTIVES: Data concerning rates of gastrointestinal (GI) events in non
steroidal anti-inflammatory drug (NSAID) users derive mainly from clinical
trials. The EVIDENCE study quantified the incidence of symptomatic uncomplicated
and/or complicated GI events in at-risk European patients treated with NSAIDs in
real-life practice. METHODS: This non-interventional study assessed 4144 adults
with at least one GI risk factor who recently initiated NSAID therapy for
osteoarthritis (85%), rheumatoid arthritis (11%), ankylosing spondylitis (3%) or
a combination (1%). Patient characteristics and medical history were collected
from medical records. GI events (upper and lower) were recorded at in-clinic
visits during 6 months' follow-up. RESULTS: Mean time on index NSAID at enrolment
was 33 days. The incidence (per 100 person-years) was 18.5 per 100 person-years
for uncomplicated GI events and 0.7 per 100 person-years for complicated GI
events. Upper GI events were far more common (12%) than lower GI events (1%)
during study follow-up (median 182 days (range 61-320)). Other reported rates for
cardiovascular, anaemia or non-GI events were much less frequent. A minority
(28%) of patients had ongoing proton pump inhibitor use at enrolment, with strong
variation by practice and country. CONCLUSIONS: EVIDENCE is the largest
prospective study of the real-life management of European patients treated with
NSAIDs for rheumatic diseases and at increased GI risk. It shows that GI events
from the upper GI tract are far more common than those from the lower GI tract.
It also shows adherence to guidelines for gastroprotection is generally low.
CLINICALTRIALSGOV IDENTIFIER: NCT01176682.
PMID- 24351519
TI - How familiar are clinician teammates in the emergency department?
AB - OBJECTIVES: Lack of familiarity between teammates is linked to worsened safety in
high risk settings. The emergency department (ED) is a high risk healthcare
setting where unfamiliar teams are created by diversity in clinician shift
schedules and flexibility in clinician movement across the department. We sought
to characterise familiarity between clinician teammates in one urban teaching
hospital ED over a 22 week study period. METHODS: We used a retrospective study
design of shift scheduling data to calculate the mean weekly hours of familiarity
between teammates at the dyadic level, and the proportion of clinicians with a
minimum of 2, 5, 10 and 20 h of familiarity at any given hour during the study
period. RESULTS: Mean weekly hours of familiarity between ED clinician dyads was
2 h (SD 1.5). At any given hour over the study period, the proportions of
clinicians with a minimum of 2, 5, 10 and 20 h of familiarity were 80%, 51%, 27%
and 0.8%, respectively. CONCLUSIONS: In our study, few clinicians could be
described as having a high level of familiarity with teammates. The limited
familiarity between ED clinicians identified in this study may be a natural
feature of ED care delivery in academic settings. We provide a template for
measurement of ED team familiarity.
PMID- 24351520
TI - Non-resuscitative first-aid training for children and laypeople: a systematic
review.
AB - BACKGROUND: Relatively little is currently known about the effectiveness of first
aid training for children and laypeople. We have undertaken a systematic review
to synthesise the evidence and inform policy and practice in this area. METHODS:
A range of bibliographic databases were searched. Studies were eligible if they
used experimental designs, provided first-aid training to laypeople or children
and reported first-aid knowledge, skills behaviours or confidence. Studies were
selected for inclusion, data extracted and risk of bias assessed by two
independent reviewers. Findings were synthesised narratively. RESULTS: 23 studies
(14 randomised controlled trials and 9 non-randomised studies) were included, 12
of which recruited children or young people (<=19 years old). Most studies
reported significant effects favouring the intervention group; 11 out of 16
studies reported significant increases in first-aid knowledge; 11 out of 13
studies reported significant increases in first-aid skills; 2 out of 5 studies
reported significant improvements in helping behaviour; and 2 out of 3 studies
reported significant increases in confidence in undertaking first aid. Only one
study undertook an economic evaluation; finding an intensive instructor-led
course was more effective, but had significantly higher costs than either a less
intensive instructor-led course or a video-delivered course. Most studies were at
risk of bias, particularly selection, performance or detection bias. CONCLUSIONS:
There is some evidence to support provision of first-aid training, particularly
for children or young people, but many studies were judged to be at risk of bias.
Conclusions cannot be drawn about which first-aid training courses or programmes
are most effective or the age at which training can be most effectively provided.
Few studies evaluated training in adult laypeople. High-quality studies are
required assessing effectiveness and cost-effectiveness of standardised first-aid
training to inform policy development and provision of first-aid training.
PMID- 24351521
TI - Improvised shoulder reduction: a useable method.
PMID- 24351522
TI - Excited delirium as a potentially dangerous diagnosis.
PMID- 24351523
TI - Characterising emergency department high-frequency users in a rural hospital.
AB - OBJECTIVE: Patients who are frequent users (>=4 visits/year) comprise ~10% of
patients, but account for ~34% of total yearly emergency department (ED) visits.
Non-emergent care provided to frequent ED users affects operating costs and
usage. The majority of reports characterising frequent ED use are from urban
teaching centres. This study describes frequent users of ED services in a rural
community setting and the association between counts of patient's visits and
discrete diagnoses. DESIGN: Retrospective study of 1652 frequent ED adult
patients from a rural US hospital over a one-year period. Descriptive statistics
and Poisson regression were used to explore the characteristics of frequent users
and their patterns of diagnoses. RESULTS: Frequent user visits ranged from 4 to
66 per patient. Frequent users were 9.41% of patient volume accounting for 33.94%
of the total visits and were younger compared with patients with <4 visits.
Approximately 36% of frequent user visits were generated by 20 diagnoses when the
diagnoses were concatenated into domains which covered ~76% of the visits. There
was a high correlation between the number of visits and discrete diagnoses in
frequent users. CONCLUSIONS: These findings suggest a more complex picture of
rural ED services and their relationship with primary care and dental services,
which needs to be defined before policy development to reduce ED use.
PMID- 24351524
TI - Areolae of the placenta in the Antarctic minke whale (Balaenoptera bonaerensis).
AB - In this study, we examined the existence and structure of areolae and the
steroidogenesis of areolar trophoblast cells in the Antarctic minke whale
placenta morphologically and immunohistochemically. Placentas were collected from
the 15th, 16th and 18th Japanese Whale Research Program under Special Permit in
the Antarctic (JARPA) and 1st JARPA II organized by the Institute of Cetacean
Research in Tokyo, Japan. The opening and cavity of fetal areolae formed by
taller columnar trophoblast cells (areolar trophoblast cells) with long
microvilli and a bright cytoplasm, as compared with the trophoblast cells of the
chorionic villi interdigitating with the endometrial crypts, were recognized in
observations of serial sections. The opening of the areolar cavity was hidden by
chorionic villi with areolar trophoblast cells. Furthermore, a closed pouch-like
structure lined by tall columnar cells similar to areolar trophoblast cells
within the stroma of chorionic villi was noticed and continued to the areolar
cavity, with the opening seen on serial sections. In a surface investigation of
the chorion and endometrium by SEM, maternal (endometrial) areolae irregularly
surrounded by endometrial folds were obvious. Moreover, we distinguished areolar
trophoblast cells with long microvilli attached with many blebs from trophoblast
cells. In our immunohistochemical observations, a steroidogenic enzyme,
cytochrome P450 side chain cleavage enzyme (P450scc), was detected with strong
immunoreactivity in trophoblast cells. However, areolar trophoblast cells showed
weak or no immunoreactivity for P450scc.
PMID- 24351525
TI - Forensic evaluation of medical liability cases in general surgery.
AB - Although medical liability (disciplinary, civil and criminal) is increasingly
becoming an issue, few studies exist, particularly from the perspective of
forensic science, which demonstrate the extent to which medical malpractice
occurs, or when it does, the reasons for it. Our aims were to evaluate the
current situation concerning medical liability in general surgery (GS) in
Portugal, the reasons for claims, and the forensic evaluations and conclusions,
as well as the association between these issues and the judicial outcomes. We
analysed the Medico-Legal Council (CML) reports of the National Institute of
Legal Medicine and Forensic Sciences of Portugal related to GS during 2001-2010.
The judicial outcomes of each case were requested from the Public Prosecutor
Office (PPO) and the court. Alleged cases of medical liability in GS represented
11.2% of the total cases analysed by the CML. We estimated that in Portugal,
4:100,000 surgeries are subject to litigation. The majority of complaints were
due to the patient's death (75.4%), with laparoscopic cholecystectomy surgeries
representing 55.2% of cases. In 76.1% of the cases, the CML believed that there
was no violation of legesartis and in 55.2% of cases, no causal nexus was found
between the medical practice and the alleged harm. The PPO prosecuted physicians
in 6.4% of the cases and resulted in one conviction. Finally, the importance of
the CML reports as a relevant technical-scientific tool for judicial decision was
evident because these reports significantly (p < 0.05) influenced the
prosecutor's decision, whether to prosecute or not.
PMID- 24351526
TI - Characterization of cardiac dysfunction in sepsis: an ongoing challenge.
AB - Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs
in patients with severe sepsis and septic shock. The clinical characterization of
SIC has been largely concept-driven. Heart function has traditionally been
evaluated according to two basic conceptual models: a hydraulic pump system,
whereby the output from the heart is entirely dependent on its input, or a
hemodynamic pump, whereby the cardiac output is a function of preload, global
ventricular performance, and afterload. Minimal attention has been given to the
intrinsic contractile function of the heart or to the interaction between the
peripheral circulation and the intrinsic myocardial function in sepsis.
Currently, SIC is assumed to be the result of the interaction of microorganisms
that activate the physiopathological pathways and cellular signaling mechanisms
that lead to intrinsic myocardial dysfunction. However, the animal models used to
study SIC exhibit multiple limitations. This review addresses the conceptual
background, historical perspectives, physiologic mechanisms, current evidence,
and limitations of SIC characterization. It also highlights potential future
directions for the hemodynamic assessment of the intrinsic contractile function
of the heart to overcome current methodological limitations. Finally, the present
review recommends the exploration of additional potential mechanisms underlying
SIC.
PMID- 24351527
TI - Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous
thromboembolism prophylaxis.
AB - BACKGROUND: Venous thromboembolism (VTE) prophylaxis remains debated following
trauma, and recommendations have not been established. Although
hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to
thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of
hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore,
we hypothesized that heparin is less effective for VTE prophylaxis following
severe injury due to hyperfibrinogenemia. METHODS: In vitro studies evaluated
thromboelastography (TEG) parameters in 10 healthy volunteers after the addition
of fibrinogen concentrate and heparin. Data from a recent randomized controlled
trial, conducted at an academic level I trauma center surgical intensive care
unit, were reviewed. Critically injured patients were randomized to standard VTE
prophylaxis (5,000 U low-molecular-weight heparin daily) or TEG-guided
prophylaxis (up to 10,000 U low-molecular-weight heparin daily) and were followed
up for 5 days. Analysis was performed to evaluate the relationship between
fibrinogen levels, measures of anticoagulation, and TEG parameters. RESULTS: In
vitro studies revealed increased fibrinogen reversed the effects of heparin as
measured by TEG. Fifty patients were enrolled in the clinical study with 25 in
each arm. Thromboelastography parameters, fibrinogen, platelet count, and anti-Xa
levels did not differ between groups despite treatment provided. Fibrinogen
levels increased over the 5-day study period (597 +/- 24.0 to 689.3 +/- 25.0), as
well as clot strength (9.8 +/- 0.4 to 14.5 +/- 0.6), which had a significant
correlation coefficient (P < 0.01). Moreover, there was a moderate inverse
correlation between fibrinogen level and the effect of heparin (RF), which was
significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin
resistance. CONCLUSIONS: Hypercoagulability and heparin resistance are common
following trauma. The preclinical and clinical relationships between fibrinogen
levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor
in heparin resistance.
PMID- 24351528
TI - Differential changes in hepatic synthesis of albumin and fibrinogen after severe
hemorrhagic shock in pigs.
AB - INTRODUCTION: Changes of plasma albumin and fibrinogen after various insults have
been described as acute phase responses. This study investigated the acute
changes of hepatic synthesis of albumin and fibrinogen after hemorrhage and
resuscitation with lactated Ringer's (LR) solution or normal saline (NS) in pigs.
METHODS: Twenty anesthetized pigs were randomized into control (n = 6), LR
solution (n = 7), and NS (n = 7) groups. Hemorrhage of 60% estimated blood volume
was induced in the LR and NS groups by removing blood from the left femoral
artery with a computer-controlled pump, followed by resuscitation with either LR
solution at three times the bled volume, or NS to reach the same mean arterial
pressure as in the LR group. Stable isotope 1-C-phenylalanine was infused for 6 h
with hourly blood sampling and subsequent gas chromatography and mass
spectrometry analysis to quantify hepatic protein synthesis. RESULTS: Hemorrhage
decreased mean arterial pressure and increased heart rate. Resuscitation with LR
solution or NS corrected these changes. Compared with baseline, hemorrhage and
resuscitation decreased albumin levels to 49% +/- 2% and 44% +/- 3% and
fibrinogen levels to 50% +/- 2% and 53% +/- 2% in LR solution and NS (all P <
0.05), respectively. Albumin synthesis was impaired from 8.8 +/- 1.4 mg/kg per
hour (control) to 5.3 +/- 0.8 mg/kg per hour in LR solution and 3.9 +/- 0.6 mg/kg
per hour in NS (both P < 0.05). No changes were observed in fibrinogen synthesis
after hemorrhage and resuscitation with LR solution (4.4 +/- 0.7 mg/kg per hour)
or NS (3.3 +/- 0.4 mg/kg per hour), compared with the control (3.5 +/- 0.3mg/kg
per hour). CONCLUSIONS: Hemorrhage and resuscitation compromised albumin
synthesis, but not fibrinogen synthesis. There were no differences in hepatic
synthesis of albumin or fibrinogen between LR solution and NS resuscitation.
PMID- 24351530
TI - [Evaluation of the balance between energy supplement and consumption in patients
with serious burn: a problem worth further investigation].
AB - The energy expenditure of burn patients can be determined accurately by indirect
calorimetry measurement, or estimated approximately with energy expenditure
equations. However, the energy requirement is not entirely equal to energy
expenditure in the whole process of burn injury. The energy consumption induced
by hyper catabolism is increased significantly, and on the other hand, the
ability of nutrient absorption and anabolism decreased remarkably in the early
phase of burn injury, thus leading to imbalance between energy consumption and
demand. However, energy supplement as calculated according to energy consumption
may induce overfeeding in the early phase of burn injury. Excessive nutrients
intake can not be fully utilized to decrease hypermetabolic reaction, but it
might exacerbate metabolic disorder. Therefore, the energy supplement should be
lower than energy consumption during the early stage of burns. With the advance
of disease course, the internal environment becomes stable gradually, ending in a
balance between anabolism and catabolism. Energy supplement should be increased
gradually according to energy consumption. During the convalescent period,
anabolic metabolism exceeds catabolic metabolism, therefore the quantity of
energy supplement should be moderately higher than that of energy consumption.
Thus, the energy consumption and energy supplement may reach a balance during the
whole course of treatment. The purpose of the article is to analyze and discuss
how to estimate energy expenditure precisely and evaluate energy requirement
correctly, in order to reach a balance between energy consumption and supplement
during a long course of treatment for severe burn patients.
PMID- 24351531
TI - [Metabolic response and dynamic nutrition support after trauma].
AB - Trauma can induce a series of dynamic metabolic responses with different
characteristics in three stages, including ebb phase, flow phase, and recovery
phase. Nutrition support after trauma should be dynamically adjusted according to
metabolic response and its individual phase, focusing on energy balance as well
as metabolic modulation, adjusting immunological response to trauma by reduction
of the exaggerated cytokines production, maintaining body protein balance, and
enhancing wound healing.
PMID- 24351529
TI - Adjusting the compass: new insights into the role of angiogenesis in Alzheimer's
disease.
AB - Growing evidence suggests that vascular perturbation plays a critical role in the
pathogenesis of Alzheimer's disease (AD). It appears to be a common feature in
addition to the classic pathological hallmarks of amyloid beta (Abeta) plaques
and neurofibrillary. Moreover, the accumulation of Abeta in the cerebral
vasculature is closely associated with cognitive decline, and disruption of the
blood-brain barrier (BBB) has been shown to coincide with the onset of cognitive
impairment. Although it was originally hypothesized that the accumulation of
Abeta and the subsequent disruption of the BBB were due to the impaired clearance
of Abeta from the brain, a body of data now suggests an alternative hypothesis
for vascular dysfunction in AD that amyloidogenesis promotes extensive
neoangiogenesis leading to increased vascular permeability and subsequent
hypervascularization. In this review, we discuss the role Abeta plays in
angiogenesis of the neurovasculature and BBB and how it may contribute to the
pathogenesis of AD. These studies suggest that interventions that directly or
indirectly affect angiogenesis could have beneficial effects on amyloid and other
pathways in AD.
PMID- 24351532
TI - [Effects of panthenol-glutamine on intestine of rats with burn injury and its
dose-effect relationship].
AB - OBJECTIVE: To study the effects of the panthenol-glutamine on intestinal damage
and motor function of intestine in rats with burn injury as well as its dose
effect relationship. METHODS: (1) Experiment 1. Ninety SD rats were divided into
groups A-I according to the random number table, with 10 rats in each group. Rats
in groups A-I were inflicted with 30% TBSA full-thickness burn and fed by gavage
with panthenol and glutamine at post injury hour (PIH) 4, in the whole dosage of
1.00 and 4, 0.50 and 4, 0.25 and 4, 1.00 and 2, 0.50 and 2, 0.25 and 2, 1.00 and
1, 0.50 and 1, 0.25 and 1 g.kg(-1).d(-1). The feeding was carried out twice a day
to achieve the total dosage in 7 days. On drug withdrawal day, blood and
intestinal tissue were harvested to detect the intestinal propulsion index,
diamine oxidase (DAO) activity in serum, and the content of acetylcholine and
intestinal mucosa protein. The best proportion of panthenol and glutamine was
screened. (2) Experiment 2. Seventy SD rats were divided into normal control
(NC), burn (B), burn+panthenol (B+P), burn+glutamine (B+G), and burn+low,
moderate, or high dose of panthenol-glutamine (B+LPG, B+MPG, B+HPG) groups
according to the random number table, with 10 rats in each group. Rats in the
latter 6 groups were inflicted with 30% TBSA full-thickness burn. Rats in the
latter 5 groups were fed by gavage with panthenol and (or) glutamine at PIH 4.
Rats in group B+P were fed with panthenol for 1 g.kg(-1).d(-1), rats in group B+G
with glutamine for 4 g.kg(-1).d(-1), rats in groups B+LPG, B+MPG, and B+HPG with
panthenol and glutamine in the dosage of 0.50 and 2, 1.00 and 4, 2.00 and 8 g.kg(
1).d(-1). The feeding was carried out twice a day to achieve the total dosage for
7 days. The indexes and time point for observation were the same as those of
experiment 1. Meanwhile, the pathological change in intestine was observed. The
same process was carried out in the rats of group NC. Data were processed with
factorial designed analysis of variance (ANOVA), one-way ANOVA and Fisher's exact
probability test. LSD was applied for paired comparison. RESULTS: (1) The values
of intestinal propulsion index and intestinal mucosa protein content in groups A
and B were close (with P values all above 0.05), and were significantly higher
than those of the other 7 groups (with P values all below 0.01). Content of
acetylcholine in group A was significantly higher than that of the other 8 groups
(with P values all below 0.01). DAO activity in groups A, D, and E was close in
value (with P values all above 0.05), and all of the values were significantly
lower than those of the other 6 groups (with P values all below 0.01). The best
proportion of panthenol and glutamine was 1.00 and 4 g.kg(-1).d(-1). (2) Compared
with those of group NC, the intestinal propulsion index, the contents of
acetylcholine and intestinal mucosa protein were decreased significantly, while
the DAO activity obviously increased in group B (with P values all below 0.01);
the intestinal propulsion index was decreased significantly in group B+P (P <
0.01); the intestinal propulsion index and content of acetylcholine were
decreased significantly in group B+G (with P values all below 0.01); the
intestinal propulsion index was decreased significantly in group B+LPG (P <
0.01); no obvious change was observed in groups B+MPG and B+HPG (with P values
all above 0.05). Compared with those of group B [0.50 +/- 0.07, (69 +/- 10)
ug/mL, (26 +/- 11) ug/g, (0.672 +/- 0.145) U/mL], the contents of acetylcholine
and intestinal mucosa protein were increased significantly, DAO activity
decreased significantly in group B+P (with P values all below 0.01); the contents
of intestinal mucosa protein was increased significantly, DAO activity decreased
significantly in group B+G (with P values all below 0.01); the contents of
acetylcholine and intestinal mucosa protein were increased significantly in group
B+LPG (with P values all below 0.01); the intestinal propulsion index, the
contents of acetylcholine and intestinal mucosa protein were increased
significantly, while the DAO activity obviously decreased in groups B+MPG and
B+HPG [0.66 +/- 0.07, 0.68 +/- 0.05; (163 +/- 24), (168 +/- 15) ug/mL; (57 +/-
7), (57 +/- 7) ug/g; (0.203 +/- 0.070), (0.193 +/- 0.068) U/mL, with P values all
below 0.01]. The levels of the four indexes in groups B+MPG and B+HPG were close
or the same in values (with P values all above 0.05). Compared with those of
group B, the numbers of rats with irregularly arranged villi in group B+P were
decreased significantly (P < 0.05); the numbers of rats with villi decreased in
height, irregularly arranged villi, and neutrophil infiltration in group B+G were
decreased significantly (with P values all below 0.05); the numbers of rats with
villi decreased in height, irregularly arranged villi, degeneration and necrosis
of cells, and neutrophil infiltration in group B+LPG were decreased significantly
(with P values all below 0.05); the numbers of rats with villi decreased in
height and number, irregularly arranged villi, degeneration and necrosis of
cells, and neutrophil infiltration in groups B+MPG and B+HPG were decreased
significantly (with P values all below 0.05). There was no statistically
significant difference between group B+HPG and group B+MPG for the former
mentioned five indexes (with P values all above 0.05). CONCLUSIONS: Combined
application of panthenol and glutamine can obviously reduce intestinal mucosa
damage and promote gastrointestinal motility of rats with burn injury, and they
show curative effect superior to exclusive use of either of the two drugs. The
best proportion of panthenol and glutamine is 1.00 and 4 g.kg(-1).d(-1).
PMID- 24351533
TI - [Evaluation of the heterogeneity of systematic reviews on nutrition support for
burn patients with Meta-regression algorithm].
AB - OBJECTIVE: To evaluate the heterogeneity of systematic reviews (SRs) on nutrition
support for burn patients with Meta-regression algorithm quantitatively. METHODS:
SRs on nutrition support for burn patients since 1980 were searched in 7
databases, including PubMed, EMBASE on CD, Science Citation Index, Cochrane
Library, Chinese Biomedicine Database, Chinese Medical Current Contents, and
Chinese Journal Full-text Database. SRs were identified with inclusion criteria:
the research was interventive SR or Meta analysis of clinical data of burn
patients aged equal to or over 18 years who had received clinical nutrition
intervention, with regimen including special nutrient given including enterally
or parenterally; the outcome indicator was mortality. A two-step method was
established to evaluate the heterogeneity of SRs. (1) Qualitative analysis: the
publication time of SRs and the trial design, patient type, regimen or route of
nutrition therapy, energy intake, and outcome reported by the included clinical
trial were analyzed. (2) Quantitative analysis: a mortality Meta-regression model
was established by trial design, publication time, regimen or route of nutrition
therapy, and energy intake to calculate the expected mortality.
Observation/expectation (O/E) ratio and its 95% confidence interval were
calculated to identify the heterogeneity among the clinical trials of SRs.
RESULTS: (1) Six SRs were retrieved which were published within 10 years. Only
three SRs reported two of the three important parameters of nutrition
intervention: regimen or route of nutrition therapy, energy intake, and clinical
outcome. Totally, 11 clinical trials that gave outcome information were included
in the SRs, including 10 RCTs and 1 case control trial. (2) Meta-regression
analysis showed that significant heterogeneity existed in 4 RCTs (including five
study groups), which were different from the other 7 trials. The patient samples
of these 4 RCTs were from different population. No heterogeneity was detected by
Meta-regression model among the three RCTs that reported regimen or route of
nutrition therapy, energy intake, and outcome. CONCLUSIONS: Quality of SRs on
nutrition intervention for burn patients is poor, and significant heterogeneity
exists among trials that are included in these SRs. O/E ratio from Meta
regression could be an effective tool to identify heterogeneity and its source.
PMID- 24351534
TI - [Effects of glutamine combined with ulinastatin on inflammatory response of
patients with severe burn injury].
AB - OBJECTIVE: To observe the effects of glutamine combined with ulinastatin on
inflammatory response of patients with severe burn injury. METHODS: Sixty
patients with severe burn injury admitted to our burn wards from January 2010 to
December 2011 conforming to the study criteria were divided into control group
(C, n = 20), glutamine group (G, n = 20), and glutamine combined with ulinastatin
group (G + U, n = 20) according to the random number table. Another 10 healthy
volunteers were chosen as normal control group (NC). Isonitrogenous and
isocaloric nutrition supports were given to patients in groups C, G, and G + U
from post burn day (PBD) 2. 0.3 g/kg protein in the form of glutamine dipeptide
was given to patients in group G for 10 days. 0.3 g/kg protein was given to
patients in group G + U for 10 days with the same amount of glutamine dipeptide
as that in group G, followed by intravenous injection of 100 kU ulinastatin (once
per 8 hours) for 7 days during 10 days. The nitrogen concentration of 24 h urine
was determined with Kieldahl nitrogen determination method, and nitrogen balance
was calculated one day before treatment and ten days after treatment. Meanwhile,
the levels of D-lactate in serum was determined by colorimetric method, the
levels of diamine oxidase (DAO), TNF-alpha, and IL-6 by enzyme-linked
immunosorbent assay, and LPS level by kinetic turbidimetric assay with TAL. Above
mentioned indexes were also examined in group NC. The wound healing rate on PBD
30, total hospital stay days, and the incidence of burn sepsis of all burn
patients were recorded. Data were processed with one-way analysis of variance,
LSD test, t test, and chi-square test. RESULTS: Compared with that in group C [(
5.40 +/- 1.67) g/d], nitrogen balance in group G was significantly increased ten
days after treatment [(-1.35 +/- 0.59) g/d, P < 0.01]. The serum levels of D
lactate, DAO, LPS, TNF-alpha, and IL-6 in group G ten days after treatment were
significantly lower than those in group C (P < 0.05 or P < 0.01). No
statistically significant difference was observed in nitrogen balance and the
serum levels of D-lactate, DAO between group G + U and group G (P values all
above 0.05). The serum levels of LPS, TNF-alpha, and IL-6 in group G + U ten days
after treatment were respectively (0.167 +/- 0.064) EU/mL, (43 +/- 14) pg/mL,
(139 +/- 23) pg/mL, which were significantly lower than those in group G [(0.240
+/- 0.079) EU/mL, (59 +/- 8) pg/mL, (195 +/- 31) pg/mL, respectively, P < 0.05 or
P < 0.01]. The would healing rate on PBD 30 and total hospital stay days in group
G were respectively higher and shorter than those in group C (P values all below
0.01), but no statistically significant difference in the incidence of burn
sepsis was found between them (P > 0.05). The would healing rate on PBD 30 in
group G+U [(96 +/- 4)%] was enhanced, and total hospital stay days [(41 +/- 4) d]
were lowered than those in group G [(88 +/- 7)%, (49 +/- 5)d, P values all below
0.01]. The incidence of burn sepsis of patients in group G + U (5%) was
significantly lower than that in group C (35%, chi(2) = 6.234, P < 0.05).
CONCLUSIONS: Glutamine combined with ulinastatin treatment can alleviate damage
to intestine after severe burn injury, lower the serum level of inflammatory
cytokines, promote wound healing, and reduce the incidence of burn sepsis.
PMID- 24351535
TI - [Structural and functional changes in islet beta cells in severely scalded rats].
AB - OBJECTIVE: To observe the structural and functional changes in islet beta cells
in severely scalded rats, and to explore its relationship with dysfunction of
glycometabolism. METHODS: Seventy-two Wistar rats were divided into scald (S)
group and sham injury (SI) group according to the random number table, with 36
rats in each group. Rats in group S were inflicted with 50%TBSA full-thickness
scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 degrees C
hot water. Rats in group SI were sham injured through immersion of back and
abdomen in 37 degrees C warm water. At post injury hour (PIH) 6 and on post
injury day (PID) 3 and 7, plasma glucose level was measured for intraperitoneal
glucose tolerance test (IPGTT) in 12 rats of each group, and the area under the
curve (AUC) of plasma glucose level was calculated. After the IPGTT, pancreatic
tissue was harvested and subjected to a double immunostaining for insulin and
cell nuclei to determine the pancreatic insulin-positive area ratio, and the area
and number of beta cells in the islets (referred to as "the three indicators in
the islets"). Data were processed with the analysis of repeated measures and
factorial designed analysis of variance, and LSD test was applied for paired
comparison. RESULTS: (1) At PIH 6 and on PID 3, the overall plasma glucose levels
of rats in group S before and after injection of glucose and at each time point
were obviously higher than those of rats in group SI (with F values of main
effects respectively 79.372 and 32.962, P values all below 0.001; with P values
of paired comparison below 0.05 or 0.01). On PID 7, the overall plasma glucose
levels in the two groups before and after injection of glucose and at each time
point were close (with P values all above 0.05). (2) The overall AUC of plasma
glucose levels of rats in group S was higher than that of rats in group SI (main
effects: F = 337.87, P < 0.01). Compared with those of rats in group SI [(1019 +/
32), (1003 +/- 72) mmol.min.L(-1)], the AUCs of plasma glucose levels of rats in
group S were higher at PIH 6 and on PID 3 [(1501 +/- 163), (1132 +/- 67)
mmol.min.L(-1), P values all below 0.001]. The AUCs of plasma glucose levels were
close between two groups on PID 7 (P > 0.05). The AUCs of plasma glucose levels
on PID 3 and 7 were both lower than that at PIH 6 in rats of group S (with P
values all below 0.001). (3) The three indicators in the islets in rats of group
S were all lower than those of rats in group SI (with F values of main effects
respectively 135.17, 24.75 and 39.35, P values all below 0.01). There were no
significant differences in the three indicators in the islets at PIH 6 between
two groups (with P values all above 0.05). The three indicators in the islets of
rats in group S on PID 3 and 7 [0.47 +/- 0.05, 0.51 +/- 0.07; (0.032 +/- 0.008),
(0.037 +/- 0.008) mm(2); (303 +/- 64), (341 +/- 58) cells] were significantly
lower than those of rats in group SI [0.63 +/- 0.05, 0.64 +/- 0.06; (0.043 +/-
0.011), (0.044 +/- 0.012) mm(2); (398 +/- 112), (387 +/- 90) cells; P < 0.05 or P
< 0.01] and that at PIH 6 within group S (P < 0.05 or P < 0.01). CONCLUSIONS: The
number of beta cells is reduced, and the insulin secretion function of beta cells
is decreased in the scalded rats, and they may constitute the cause of
dysfunction of glycometabolism, mainly manifested as hyperglycemia.
PMID- 24351536
TI - [Influence of the depth of retained denatured dermis on the survival rate of
grafted skin in burn swine with deep partial-thickness burn].
AB - OBJECTIVE: To explore the influence of the thickness of retained denatured dermis
on the survival rate of grafted skin in swine with deep partial-thickness burn.
METHODS: Four deep partial-thickness wounds were reproduced respectively on both
sides of spine in 7 Chinese domestic pigs. The wounds of 6 pigs were divided into
0.25, 0.50, 0.75, and 1.00 mm groups with 12 wounds in each group according to
the random number table. Tangential excision and auto-skin grafting were
performed. Before the tangential excision, 1 tissue specimen was harvested from
the center of each remaining wound for the estimation of the depth of burn, and
histological observation was done. After the tangential excision, 1 tissue
specimen was harvested from the area near the center of each wound for the
measurement of the depth of retained denatured dermis with histological
examination. The 8 wounds of one pig were set as the control group, and the
operation was done, and then they were treated with exposure treatment after
biopsy specimens were taken with above-mentioned method. The general condition of
wounds in 5 groups was observed from immediately after injury to post injury
month (PIM) 3. On post injury day (PID) 7, the survival rate of grafted skin was
observed in 0.25, 0.50, 0.75, and 1.00 mm groups. Wound healing time was
recorded. At PIM 3, the specimens were harvested from the wounds of 5 groups, and
their ultra microstructures were observed by transmission electron microscope.
Data were processed with rank-sum test, one-way analysis of variance, and LSD
test. RESULTS: The depth of the burn tissue was (1.120 +/- 0.211) mm. The depths
of retained denatured dermis in 0.25, 0.50, 0.75, and 1.00 mm groups were
respectively (0.830 +/- 0.031), (0.701 +/- 0.010), (0.382 +/- 0.031), and (0.141
+/- 0.040) mm. At PID 8, all grafted skin in 0.25 and 0.50 mm groups became
necrotic; most grafted skin in 0.75 mm group was necrotic; most grafted skin in
1.00 mm group survived with only a few became necrotic and separated from the
wounds. The scabs were gradually separated from the wounds of control group. On
PID 15, the grafted skin which did not survive in 0.25, 0.50, and 0.75 mm groups
was gradually separated from the wounds with exudate forming scab on the surface
in varying degrees, while the wounds in 1.00 mm group were all healed, and the
incidence of scabs formation was highest in control group. At PIM 3, scar
contraction was found in 0.25, 0.50, 0.75 mm groups and control group, while no
obvious scar was observed in 1.00 mm group. There were statistically significant
differences in the survival rate of grafted skin in 0.25, 0.50, 0.75, and 1.00 mm
groups (chi(2) = 19.421, P < 0.001). The survival rate was the highest in 1.00 mm
group [70% (60%, 80%)], while the survival rate was 20% (0, 30%) in 0.75 mm
group, and it was in both 0.25 and 0.50 mm groups with non-survival of all the
grafted skin. There were statistically significant differences in the wound
healing time among 5 groups (F = 41.450, P < 0.001). The wound healing time in
0.25 and 0.50 mm groups were respectively (18.2 +/- 1.5), and (18.7 +/- 2.3) d,
not statistically significant different from that of control group [(18.4 +/-
1.7) d, P values both above 0.05]. The wound healing time in 0.75 mm group [(14.9
+/- 2.6) d] was significantly different from those of 0.25, 0.50 mm groups and
control group (P values all below 0.01). The wound healing time in 1.00 mm group
[(9.5 +/- 1.2) d] was significantly shorter compared with that of the other 4
groups (P values all below 0.01). Before tangential excision, the zone of
infiltration of the inflammatory cells was observed in the deep dermis of wounds
in 5 groups. After tangential excision and before auto-skin grafting, the depth
from the fault surface to the zone of infiltration of the inflammatory cells
varied in 0.25, 0.50, 0.75, and 1.00 mm groups while more inflammatory cells were
observed in control group. At PIM 3, many fibroblasts were observed in the dermis
of wounds in 1.00 mm group with abundant rough endoplasmic reticulum and
basically intact organelles. CONCLUSIONS: Performing autologous skin grafting on
deep partial-thickness burn, in which the depth of retained denatured dermis was
0.10 mm, may help regenerate dermal function and alleviate scar formation.
PMID- 24351537
TI - [Advances in the research of treatment of hydrofluoric acid burn].
AB - Hydrofluoric acid (HF) is one of the most common inorganic acids used widely in
industrial circle. HF not only causes cutaneous burn, but also induces systemic
toxicity by its unique injury mechanism. Accurate and timely diagnosis and
treatment are critical after HF burns. To date, the strategies for treating HF
burns have been developed, mainly including topical treatments and systematic
support. However, there is no standard treatment strategy with wide acceptance in
the world. This paper presents a comprehensive overview of the advances in the
research of strategies for the treatment of HF burns.
PMID- 24351538
TI - [Advances in the research of the role of MicroRNAs in wound healing].
AB - MicroRNAs are endogenous noncoding RNA molecules with 19-22 nucleotides in
length. MicroRNAs can post-transcriptionally regulate gene and (or) protein
expression by binding to their target messenger RNAs (mRNAs), leading to mRNA
degradation or suppression of translation. As a huge family that regulates gene
expression, microRNAs has recently been shown to not only participate in the
normal healing processes of wounds but also closely related to pathologic wound
healing, and formation of hypertrophic scars and keloids. This review focuses on
the biogenesis of microRNA and its role in wound healing.
PMID- 24351539
TI - [Advances in the research of the effect of toll-like receptor in the formation of
keloid].
AB - Keloid is a kind of pathological scar of skin, which would seriously impair
patient's quality of life. But until today, no reliable theory to explain the
development of keloid has been established. Recent studies have found that toll
like receptors plays an important role in the formation of keloid. This article
reviews the advances in the research of toll-like receptors making contribution
to the pathogenesis of keloid. Further researches could lead to a new strategy in
treating keloid.
PMID- 24351540
TI - The retinoblastoma protein and PML collaborate to organize heterochromatin and
silence E2F-responsive genes during senescence.
AB - Cellular senescence is characterized by silencing of genes involved in DNA
replication and cell cycle progression. Stable repression is crucial for
preventing inappropriate DNA synthesis and the maintenance of a prolonged
senescent state. Many of these genes are targets for E2F transcription factors.
The pRB pathway plays a major role in senescence by directly repressing E2Fs and
also by regulating chromatin at the promoters of E2F target genes using its LXCXE
cleft-dependent interactions. In this study, we sought to investigate the
mechanisms by which pRB stably silences E2F target gene transcription during
cellular senescence. We report that in mouse embryonic fibroblasts, endogenous
promyelocytic leukemia protein (PML) associates with E2F target genes in a pRB
LXCXE-dependent manner during HrasV12-induced senescence. Furthermore, using a
PML-IV-induced senescence model, we show that the pRB LXCXE binding cleft is
essential for PML association with gene promoters, silencing of E2F target genes,
and stable cell cycle exit. Binding assays show that pRB can interact with PML
specifically during senescence, suggesting that signaling events in senescence
regulate assembly of PML and pRB to establish heterochromatin and create a
permanent cell cycle arrest.
PMID- 24351541
TI - Maternal smoking-A contributor to the obesity epidemic?
AB - SUMMARY: The prevalence of obesity is increasing worldwide, and the rising number
of obese children and adolescents is of particular concern. In humans, smoking is
a predisposing factor for abdominal obesity, glucose intolerance and insulin
resistance. Maternal smoking is associated with preterm birth and low birth
weight. On the other hand, the incidence of obesity is higher in children and
adults born of smoking mothers. Disorders in eating behaviour, reduced physical
activity, and increased risk of hypertension and nicotine addiction have been
observed in the offspring of smoking mothers. Evidence from animal and human
studies suggests that intrauterine smoke exposure may alter peripheral and
central mediators involved in the regulation of appetite and energy metabolism.
Smoking cessation during pregnancy is desirable to improve health outcomes in
offspring.:
PMID- 24351542
TI - Results from a randomized controlled trial comparing two low-calorie diet
formulae.
AB - SUMMARY: BACKGROUND: Very low and low-calorie diets ((V)LCD) are commonly used
in the early phase of obesity treatment programmes. Recently, a new formula,
Allevo((r)), was introduced in Scandinavia. No study has hitherto assessed its
efficacy compared to the commonly used (V)LCD Nutrilett((r)). OBJECTIVE: To
compare Allevo((r)) with Nutrilett((r)) regarding short-term effects on weight
and BMI loss, ketonaemia, compliance, and body composition. DESIGN: Thirty-six
males (baseline: age 46.5 +/- 10.9 year; BMI 39.2 +/- 3.8 kg/m(2); %BF 38.8 +/-
3.9%) participated in a randomized trial comparing two LCDs, differing mainly in
protein and dietary fibre composition. Body composition was measured by DXA at
baseline and end, while body weight was measured weekly during the 8-week (V) LCD
intervention. The main outcome measures were weight, BMI, waist-circumference
(WC), and body fat percentage (%BF). RESULTS: No significant differences between
groups in age, weight, blood pressure, or %BF were observed at baseline (all p >
0.3). The mean BMI change over the study period was -4.4 +/- 0.3 and -4.2 +/- 1.9
kg/m(2) for Nutrilett((r)) and Allevo((r)), respectively (p = 0.72), while WC was
reduced by 9.6 +/- 1.0 and 10.1 +/- 3.2 cm, respectively (p = 0.51). About 49% of
the weight loss consisted of fat. When examining the weight development during
the intervention, with the eight repeated measures, no significant difference in
the slope of the weight loss curve could be detected (p = 0.50-0.65). Ketonaemia
developed similarly in both groups, and did not correlate to weight loss.
CONCLUSION: Allevo((r)) and Nutrilett((r)) appear to have equivalent efficacy
regarding weight, BMI, WC, and %BF loss in short-term interventions.
PMID- 24351543
TI - Adenosine deaminase gene polymorphism is associated with obesity in Iranian
population.
AB - SUMMARY: OBJECTIVE: Adenosine deaminase (ADA) is a polymorphic enzyme which has
an important role in modulation of insulin bioactivity. It has been suggested
that an excess of adenosine A1 receptor activity may contribute to adiposity in
type 2 diabetes. Adenosine seems to have a role in facilitating insulin action on
the adipocytes. ADA gene polymorphism seems to contribute to the degree of
obesity in type 2 diabetes patients. AIM: The aim of this study was to examine
the role of adenosine deaminase gene polymorphism in randomly selected obese
subjects in an Iranian population. RESULTS: A significant increase in the
frequency of ADA, AA genotype was observed in obese people compared to the
controls (AA versus CA + CC, p = 0.01, OR: 3.4, 95% CI: [1.08-12.8]). There was
also a significant increase in ADA gene allele A and AA genotype frequencies in
patients with higher plasma cholesterol level compared to the normal controls (p
= 0.0007, OR: 8.4, 95% CI [1.6-41.6]; AA versus CA + CC, p = 0.005, OR: 3.0, 95%
CI [1.2-7.7], respectively). When we compared the ADA allele frequency in
patients with obesity and higher plasma cholesterol level and patients with
obesity and lower plasma cholesterol level there was also a significant
difference (p = 0.01, OR: 2.6, 95% CI [1.08-6.8]). Also we examined the
association between the frequency of ADA allele and genotype frequencies with
triglyceride (TG) levels in obese patients and normal controls. We observed a
significant increase in the ADA gene AA genotype frequency in obese patients with
TG level >=150 mg/dl compared to the normal controls (AA versus CA + CC, p =
0.008, OR: 4.5, 95% CI [1.2-18.7]). CONCLUSION: Our data is supportive of a role
for ADA in obesity and also points to its association with abnormal level of TG
and cholesterol. Also our findings recommend adenosine receptors as important
targets for new therapeutic approach in obesity and dislipidemia.
PMID- 24351544
TI - Relationship of BMI increase to eating behavior and job stress in a 2-year cohort
study of non-obese male Japanese workers.
AB - SUMMARY: OBJECTIVE: To clarify the relation of weight gain to eating behavior
and job stress through a 2-year cohort study of non-obese male Japanese workers.
METHOD: A survey of life style, eating behavior, and job stress was conducted in
2003 and 2005 using the same questionnaire. The subjects were 122 non-obese (BMI
<= 24.9 kg/m(2)) male workers aged 21-60 years (mean age 35.3 +/- 12.2 (S.D.)
years) in a manufacturing industry in 2003. BMI was calculated from height and
weight obtained from health examinations in 2003 and 2005. BMI changes over the 2
years were classified into three groups: decrease; no change or increase of BMI <
1 kg/m(2); and increase of BMI >= 1 kg/m(2). RESULTS: Weight gain over the 2
years was associated with the eating behavior of 'eating to satiety'. In the
workers who gained BMI >= 1 kg/m(2), the score for 'eating to satiety' category
increased over the 2 years, while no such trend was found in the subjects who
lost weight or gained <1 kg/m(2). The score of eating to satiety in those who
gained >=1 kg/m(2) was also correlated with the psychological stress responses of
tension/anxiety and depression, which were related to job demands positively and
job latitudes negatively. CONCLUSIONS: The present study suggests that eating to
satiety is a key eating behavior for weight gain in non-obese male Japanese
workers. The eating behavior can be affected by psychological job stress
responses such as tension/anxiety and depression. Workers feeling stressed may be
more likely to develop their eating behavior to eat much and gain weight.
PMID- 24351545
TI - Nocturia and overactive bladder in obese women: A case-control study.
AB - SUMMARY: AIMS: To estimate the prevalence and severity of nocturia and lower
urinary tract symptoms in obese women and to identify risk factors associated
with nocturia in an obese population. METHODS: We performed a case-control study
based on the registry of a university hospital obesity unit. A consecutive sample
of women with body mass index >=30 (obese) was randomly matched by age, gender
and residential county to control subjects using the computerised register of the
total population. Data were collected by a self-reported postal survey. RESULTS:
The questionnaire was completed and returned by 279/446 of the patients (62%) and
430/892 control subjects (48%). Compared to the non-obese control group, obese
women reported a significantly increased prevalence and bother of nocturia (p <
0.001), frequent urination (p < 0.001) and bothersome experience of urination (p
= 0.037). Moreover, they experienced significantly increased frequency of urinary
urgency (p < 0.001), of urge urinary incontinence (p < 0.001) and of bladder
emptying difficulties (p = 0.002). The adjusted odds ratio (95% CI) in obese
women was 2.8 (1.0-7.9) for nocturia, 4.7 (1.5-14.6) for frequent urination, 5.5
(1.7-17.2) for strong urge to empty bladder and 7.2 (2.2-23.3) for urine leakage
related to the feeling of urgency. CONCLUSION: Obese women are at substantially
increased risk for nocturia and overactive bladder symptoms.
PMID- 24351546
TI - Weight loss maintenance in women 3 years after following a 12-week structured
weight loss program.
AB - SUMMARY: Structured weight loss programs such as those using meal replacements
are associated with both short-term and long-term weight loss, but the
effectiveness of structured weight loss programs using whole foods has not been
established. The primary aim of the present study was to retrospectively
establish self-reported weight status in women, 3 years after participation in a
12-week food based structured weight loss program monitored by dietitians. The
secondary aim was to determine which factors were associated with successful
weight loss maintenance. Eighty-five of the 100 participants who completed the 12
week program participated in an 18-question telephone interview which included
self-reported weight. Weight loss from baseline was 3.8 (S.D. 5.5) kg (4.4 (S.D.
6.1) %) (P < 0.001). Overall, 61% of participants weighed less than at baseline,
13% had gained weight, and the remaining 26% had maintained their baseline
weight. From baseline, 37 (44%) participants had a clinically important weight
loss of >= 5%, and were, on average, 9.8 (S.D. 4.2) % lighter (P < 0.001). The
remaining 48 (56%) participants (weight loss < 5%) were not significantly
different to their weight at baseline (P = 0.77). We conclude that a food based
structured weight loss program monitored by dietitians, as defined by this
intervention, was associated with long-term weight loss maintenance.:
PMID- 24351547
TI - Effect of weight reduction on concentration of plasma total homocysteine in obese
Japanese men.
AB - SUMMARY: OBJECTIVE: To test whether weight reduction would lower tHcys
concentration, and whether adding exercise training to dietary weight reduction
would further reduce tHcys concentration over diet alone. DESIGN: A randomized,
controlled, prospective, 14-week weight-loss intervention. SETTING AND
PARTICIPANTS: Forty-eight obese Japanese men aged 27-66 years were assigned to 2
subgroups depending on the type of treatment: diet alone (DA) and diet plus
exercise training (DE). Concentration of tHcy was measured in frozen plasma
samples by an HPLC method. RESULTS: Body weight decreased significantly for both
groups: DA -7.8 +/- 3.2 kg and DE -9.1 +/- 3.6 kg. A significant decrease was
found in tHcys concentration of the DE group (-2.3 +/- 5.0 MUmol/L) but not of
the DA (-0.3 +/- 2.7 MUmol/L). For subjects with hyperhomocysteinemia (>=15
MUmol/L, n = 17), tHcys concentration decreased from 20.1 +/- 7.0 to 13.9 +/- 3.0
MUmol/L (p < 0.01) for the DE group (n = 8) but did not change for the DA group
(16.6 +/- 1.9 MUmol/L -> 15.4 +/- 2.3 MUmol/L, n = 9). Furthermore, to consider a
statistical phenomenon "regression to the mean", we excluded two subjects with
the highest two tHcys values of the DE group. The DE group (n = 7) still
displayed a significant reduction after the exclusion. CONCLUSIONS: A weight
reduction with diet alone did not improve tHcy levels. Adding aerobic exercise
training to a dietary weight-reduction program may be effective for a reduction
in tHcy.
PMID- 24351548
TI - Thermal avalanches near a Mott transition.
AB - We probe the volume collapse transition (DeltaV/Vo ~ 15%) between the
isostructural gamma and alpha phases (T ~ 100 K) of Ce0.9Th0.1 using the Hall
effect, three-terminal capacitive dilatometry, and electrical resistivity
measurements. Hall effect measurements confirm the itinerant ground state as the
carrier concentration increases by a factor of 7 in the alpha phase, gamma phase
(nH = 5.28 * 10(26) m(-3)), and the alpha phase (nH = 3.76 * 10(27) m(-3)). We
were able to detect a noise spectrum consisting of avalanches while slowly
varying the temperature through the hysteretic region. We surmise that the
avalanches originate from intergranular stresses at the interfaces between
partially transformed high-volume and low-volume phases. The statistical
distribution of avalanches obey power laws with energy exponent epsilon ? 1.5.
Hall effect measurements, combined with universal critical exponents, point to
short electron mean-free percolation pathways and carrier localization at phase
interfaces. Carrier localization was predicted many years ago for elemental
cerium by Johansson (1974 Phil. Mag. 30 469).
PMID- 24351549
TI - Effectiveness and feasibility of virtual reality and gaming system use at home by
older adults for enabling physical activity to improve health-related domains: a
systematic review.
AB - BACKGROUND: use of virtual reality and commercial gaming systems (VR/gaming) at
home by older adults is receiving attention as a means of enabling physical
activity. OBJECTIVE: to summarise evidence for the effectiveness and feasibility
of VR/gaming system utilisation by older adults at home for enabling physical
activity to improve impairments, activity limitations or participation. METHODS:
a systematic review searching 12 electronic databases from 1 January 2000-10 July
2012 using key search terms. Two independent reviewers screened yield articles
using pre-determined selection criteria, extracted data using customised forms
and applied the Cochrane Collaboration Risk of Bias Tool and the Downs and Black
Checklist to rate study quality. RESULTS: fourteen studies investigating the
effects of VR/gaming system use by healthy older adults and people with
neurological conditions on activity limitations, body functions and physical
impairments and cognitive and emotional well-being met the selection criteria.
Study quality ratings were low and, therefore, evidence was not strong enough to
conclude that interventions were effective. Feasibility was inconsistently
reported in studies. Where feasibility was discussed, strong retention (>=70%)
and adherence (>=64%) was reported. Initial assistance to use the technologies,
and the need for monitoring exertion, aggravation of musculoskeletal symptoms and
falls risk were reported. CONCLUSIONS: existing evidence to support the
feasibility and effectiveness VR/gaming systems use by older adults at home to
enable physical activity to address impairments, activity limitations and
participation is weak with a high risk of bias. The findings of this review may
inform future, more rigorous research.
PMID- 24351550
TI - C/EBP homologous protein drives pro-catabolic responses in chondrocytes.
AB - INTRODUCTION: Excess C/EBP homologous protein (CHOP) expression is one feature of
the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress. Here,
we focused on CHOP expression and function in chondrocytes. METHODS: We studied
human knee osteoarthritis (OA) cartilage, bovine chondrocytes cultured in
alginate and subjected to sub-lethal biomechanical injury, and knee chondrocytes
of human autopsy donors. We performed siRNA knockdown and transfection. RESULTS:
UPR activation was increased in human knee OA cartilage in situ, and in
biomechanically injured cultured chondrocytes in vitro. In normal human
chondrocytes, CHOP "gain of function" sensitized chondrocytes to IL-1beta induced
nitric oxide (NO) and matrix metalloproteinase (MMP)-3 release without inducing
these responses by itself. Excess CHOP expression, by itself, induced superoxide
production and apoptosis. Conversely, siRNA knockdown of CHOP and the UPR
specific mediator X-box binding protein (XBP1) inhibited NO release by >80% (P
<0.0005) in response to IL-1beta, and blunted MMP-3 release, whereas there were
only minimal effects of the UPR mediator GRP78 on these responses. The anti
inflammatory metabolic "super-regulator" AMP kinase (AMPK) is known to limit UPR
activation in vascular muscle cells. Here, CHOP supported the capacity of IL
1beta to suppress AMPK activity in chondrocytes. We also observed that inhibition
of AMPK activity promoted an increase in chondrocyte CHOP expression. Conversely,
pharmacologic activation of AMPK by 5-Aminoimidazole-4-carboxamide ribonucleotide
(AICAR) blunted chondrocyte CHOP expression in response to biomechanical injury.
CONCLUSIONS: Biomechanical injury and IL-1 signaling stimulate UPR activation in
chondrocytes. CHOP mediates chondrocyte catabolic and apoptotic responses to IL
1beta, and does so partly by inhibiting AMPK activity. Conversely, development of
excess CHOP activity is limited by AMPK activity in chondrocytes. Our findings
suggest a mechanism for potential chondroprotection by AICAR and other AMPK
activators. The work is of translational relevance for OA, since several drugs
that activate AMPK are already in the clinic for arthritis (for example,
allosteric AMPK activators sodium salicylate and high dose aspirin, and
methotrexate, which activates AMPK by generating AICAR).
PMID- 24351551
TI - Pharmacokinetic assessment of absorptive interaction of oral etoposide and
morphine in rats.
AB - Etoposide and morphine are well known P-glycoprotein (P-gp) substrates. The
pharmacokinetic effect of morphine on plasma etoposide concentration after the
oral concomitant use of etoposide and morphine in rats was assessed using a
population analysis approach. A P-gp substrate quinidine and the anticholinergic
drug propantheline were also administered with etoposide to compare with the
effects of morphine. Plasma etoposide concentration after oral administration was
well described using a linear 2-compartment open model with first-order kinetic
absorption from the intestine, although a flip-flop phenomenon was shown. After
administration of etoposide with morphine, an increased concentration and
extended time at maximum concentration were observed compared with the
administration of etoposide alone. However, coadministered quinidine
significantly increased the maximum concentration without changing the time of
the peak concentration of etoposide. Coadministered propantheline significantly
extended the time at maximum concentration, although no changes in the peak
concentration of etoposide were observed. These coadministered drugs resulted in
different pharmacokinetic parameters of etoposide and acted as a significant
covariate. That is, morphine and quinidine significantly increased the
bioavailability of etoposide believed to be due to competitive P-gp inhibition in
the intestine. In contrast, morphine and propantheline decreased the absorption
rate constant and were associated with the suppression of enterokinesis. These
results indicate that it is necessary to understand the effects on P-gp as well
as have information on other effects on the gastrointestinal tract, such as
enterokinesis suppression, and to appropriately assess the pharmacokinetic
interactions of the combined oral use of P-gp substrate drugs.
PMID- 24351552
TI - 3,3',4,4'-Tetrachlorobiphenyl-mediated decrease of serum thyroxine level in
C57BL/6 and DBA/2 mice occurs mainly through enhanced accumulation of thyroxine
in the liver.
AB - A single intraperitoneal injection (50 mg/kg) of 3,3',4,4'-tetrachlorobiphenyl
(CB77), a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-type polychlorinated
biphenyl, led to significant decreases in the levels of serum total thyroxine
(T4) and free T4 without increase in the level of serum thyroid-stimulating
hormone at 7 d later in both TCDD-sensitive C57BL/6 and TCDD-resistant DBA/2
mice. When [(125)I]T4 was injected into the mice 7 d after treatment with CB77,
the levels of biliary [(125)I]T4 and [(125)I]T4-glucuronide increased 90 to 120
min post injection in C57BL/6 mice, but not in DBA/2 mice, compared with levels
in the corresponding control mice. In contrast, in both strains of mice, the CB77
pretreatment led to similar changes in the levels of the [(125)I]T4 bound to the
serum transthyretin, albumin, and thyroxine-binding globulin. Consequently,
treatment with CB77 promoted the clearance of [(125)I]T4 from the serum and
further raised the steady-state volumes of distribution of [(125)I]T4, the
concentration ratio (Kp value) of the liver to the serum, and the distribution of
[(125)I]T4 in the liver in both strains of mice. The present findings indicate
that in mice, the CB77-mediated decrease in the serum T4 level occurs through
enhanced accumulation of hepatic T4 rather than through increased activity of
hepatic thyroxine-uridine 5'-diphosphate-glucuronosyltransferase(s).
PMID- 24351553
TI - Alterations of high endothelial venules in primary and metastatic tumors are
correlated with lymph node metastasis of oral and pharyngeal carcinoma.
AB - High endothelial venules (HEVs) are special blood vessels in the paracortical
region of lymph nodes (LNs) and govern lymphocyte recruitment. LN metastasis has
similarity to circulating lymphocytes homing to LNs, but the role of HEVs in the
progression of oral and pharyngeal squamous cell carcinoma (OPSCC) is unclear. In
this study, we found that HEVs experienced a series of morphological and
functional changes during OPSCC progression and were correlated with LN
metastasis. In 9 cases of 73 metastatic LNs, tumor emboli were located adjacent
to HEVs or just out of the vessels but not lymphatic channels. Gap junctions of
tumor cells close to HEVs decreased or disappeared, and gaps were left at contact
points where tumor cells attached to the HEVs. Moreover, the proliferation rate
of endothelial cells of HEVs was the highest in metastatic LNs. Finally, L
selectin was detected in both primary and metastatic tumors, and it facilitated
tumor cells adhering to LNs. In conclusion, our findings suggest that remodeled
HEVs are correlated with LN metastasis of OPSCC and play important role in this
process by preparing premetastatic soil for cancer cell metastasis.
PMID- 24351554
TI - [Strengthen application oriented arsenic toxic mechanisms research].
PMID- 24351555
TI - [The regulation mechanism of protein kinase Cdelta on arsenic liver injury caused
by coal-burning].
AB - OBJECTIVE: To investigate the effects of mRNA transcriptional and protein
expressions of protein kinase Cdelta (PKCdelta) on the development of arsenic
liver injury caused by coal-burning. METHODS: Population study:133 arsenic
exposures were selected as arsenic exposure groups including the ward non-patient
group (25 cases) , no obvious hepatopathy group (38 cases) , mild (43 cases) and
moderate to severe hepatopathy group (27 cases) from the area with endemic
arsenism in Guizhou province. Another 34 healthy residents were selected as the
control group in non-arsenic pollution village. The urine and peripheral blood
were collected from the subjects. The arsenic contents in urine and mRNA
expressions of PKCdelta in peripheral blood were detected. Animal experiment
study:thirty wistar rats were randomly by random number table divided into
control group, drinking water arsenic poisoning group and coal-burning arsenic
poisoning group (i.e., low, medium and high arsenic contaminated grain group) by
random number table method, including 6 rats in each group. The control group was
fed normally for 3 months, drinking water arsenic poisoning group and coal
burning arsenic poisoning groups were fed respectively with 10 mg/kg As2O3
solution and different concentrations (25, 50 and 100 mg/kg) of arsenic
containing feed which was persisted 3 months. The arsenic contents in urine, mRNA
expression levels of PKCdelta in peripheral blood and liver tissue and the
protein expression levels of phosphorylated protein kinase Cdelta(pPKCdelta) in
liver tissue were detected. RESULTS: The median(quartile) of arsenic contents in
urine were 25.58 (18.62-40.73), 56.66 (38.93-76.77), 64.90 (39.55- 98.37) and
75.47 (41.30-109.70) ug/g Cr respectively for the non-patient group, no obvious
hepatopathy group, mild and moderate to severe hepatopathy group. The levels were
higher than that in the control group (23.34 (17.84-37.45) ug/g Cr) (P < 0.05),
except for the ward non-patient group. The arsenic contents in rat urine were
2223.61 (472.98-3976.73), 701.16 (194.01-1300.27), 1060.94 (246.33-2585.47) and
3101.11 (1919.97-5407.07) ug/g Cr, respectively for the drinking water arsenic
poisoning group, the low, medium and high dosage arsenic grain contamination
groups, all higher than that in the control group (94.32 (22.65-195.25) ug/g Cr)
(P < 0.05) . The protein expressions of pPKCdelta in liver tissue were 324.83 +/-
25.06, 278.50 +/- 30.57, 308.83 +/- 34.67 and 326.33 +/- 35.09, which were
significantly higher than that in the control group (240.17 +/- 28.07) (P < 0.05)
. The protein expression levels of pPKCdelta in liver cell membrane were 0.49 +/-
0.06,0.33 +/- 0.05,0.37 +/- 0.06 and 0.50 +/- 0.08, which were significantly
higher than that in the control group (0.28 +/- 0.04) (P < 0.05) . The protein
expression levels of pPKCdelta in liver cell cytoplasm were 0.38 +/- 0.06,0.31 +/
0.05, 0.35 +/- 0.05 and 0.36 +/- 0.05, which were significantly higher than that
in the control group (0.24 +/- 0.05) (P < 0.05). CONCLUSION: The arsenic may
regulate protein expressions of pPKCdelta and induce its membrane translocation,
and cause the development of arsenic liver injury caused by coal-burning.
PMID- 24351556
TI - [Regulating effects of Rosa roxburghii tratt preparation on immune function in
arseniasis patients caused by coal burning].
AB - OBJECTIVE: To explore the influence of rosa roxburghii tratt preparation on
immune function of arseniasis patients caused by burning coal. METHODS: According
to the diagnosis standard for endemic arseniasis(WS/T 211-2001), 62 cases of
arseniasis patients who resided in endemic arseniasis area in Guizhou province
were selected and divided stratified randomly into two groups: rosa roxburghii
tratt juice treatment group and superoxide dismutase(SOD)-enriched rosa
roxburghii tratt juice treatment group, with 31 patients in each group.Each
patient took 120 ml/d rosa roxburghii tratt preparation or SOD-enriched rosa
roxburghii tratt orally for one month. Another 30 healthy residents from a
neighbour township 12 km away where arsenic was not prevalent were selected as
controls. A 2 ml blood and 50 ml urine samples were collected from individuals
and the urine arsenic contents, peripheral blood T-lymphocyte subsets (CD3(+),
CD4(+), CD8(+) T cell), serum immunoglobulin (IgG, IgM, IgA) and complement (C3,
C4) were detected. The differences between more than two groups on above
indicators were compared. The correlations between urinary arsenic and immune
parameters were analyzed. RESULTS: Among the rosa roxburghii tratt juice group,
SOD-enriched rosa roxburghii tratt juice before intervention group and the
control group, the levels of urine arsenic were (76.55 +/- 23.02) , (72.60 +/-
25.91) and (26.33 +/- 11.30) ug/g Cr respectively and IgG were (11.31 +/- 1.68),
(11.35 +/- 1.94) and (9.23 +/- 1.75) g/L respectively. The differences were
statistically significant(F values were 82.01, 13.82, both P values < 0.05).
After intervention with rosa roxburghii tratt preparation, the levels of urine
arsenic were (53.21 +/- 16.51) and (51.72 +/- 17.70)ug/g Cr, both decreased than
before intervention (t values were 5.80 and 3.78, both P values < 0.05). The
levels of CD3(+) were (44.47 +/- 7.14)%, (43.44 +/- 6.61)% and (70.78 +/- 5.26)%,
CD4(+) were (29.87 +/- 5.67)%, (29.42 +/- 5.87)% and (46.08 +/- 5.87)%,
CD4(+)/CD8(+) were(1.25 +/- 0.42), (1.22 +/- 0.39) and (1.79 +/- 0.26) and C4
were (0.13 +/- 0.08), (0.13 +/- 0.09) and (0.20 +/- 0.11) g/L respectively among
the two treatment group before intervention and the control group. The
differences were significant (F values were 178.04, 76.71, 23.13 and 5.26, all P
values < 0.05). After intervention, the levels of CD3(+) were (59.73 +/- 7.38)%
and (66.31 +/- 7.57)%, CD4(+) were (34.00 +/- 7.97)% and (39.11 +/- 5.81)%,
CD4(+)/CD8(+) were (1.41 +/- 0.37) and(1.58 +/- 0.26), all increased than before
intervention(t values were 12.47, 25.18, 5.41, 10.47, 3.22 and 5.05, all P values
< 0.05). The levels of urine arsenic and CD3(+), CD4(+), CD4(+)/CD8(+), C4 were
inversely correlated correlation, while positive correlation existed between the
level of urine arsenic and IgG(r values were -0.68, -0.56, -0.51, -0.43 and 0.36,
all P values < 0.01). CONCLUSIONS: The level of urinary arsenic level is closely
related to immune function suppression in arseniasis patients caused by burning
coal, rosa roxburghii tratt preparation can effectively improve immune function
of arseniasis patients.
PMID- 24351557
TI - [The mRNA expression of mitogen-activated protein kinase signal pathway related
genes in the blood of arseniasis patients caused by burning coal].
AB - OBJECTIVE: To detect the mRNA expression of ERK1, ERK2, JNK1 and P38 gene in
mitogen-activated protein kinase(MAPK) path way in the arseniasis patients caused
by burning coal. METHODS: 70 arseniasis patients caused by burning coal at Jiaole
village XingRen county in December 2006 were selected as case group, and another
30 villagers with similar living habits, matched gender and age, healthy physical
condition without history of burning high arsenic coal were selected as control
group from 12 km nearby the same village.Silver diethyl dithiocarbamate method
(Ag-DDC) was taken to detect the arsenic contents in the environmental media,
food, and arsenic level in the urine and hair of arseniasis patients.On the
principle of informed consent, the peripheral blood was collected from the
patients. The total RNA was extracted with Trizol method and cDNA was reversed
from it. The mRNA expression of ERK1, ERK2, JNK1 and P38 gene in MAPK path way
were tested by real-time fluorescent quantitative PCR (QT-PCR). RESULTS: A total
of 70 cases of arseniasis patients (31 cases of mild, 25 cases of moderate and 14
cases of severe) and 30 cases of control were chosen. The median (quartile) of
arsenic contents in the indoor air, outdoor air, coal, chili and corn were 0.079
(0.053-0.117) mg/m(3) ,0.007 (0.002-0.015) mg/m(3) , 93.010 (39.460-211.740)
mg/kg, 3.460(0.550-16.760) mg/kg and 1.500(0.300-4.140) mg/kg respectively. They
were above the national health standards. The median (quartile) of arsenic
contents in the soil, rice and drinking water were separately 12.130(4.230
24.820) mg/kg, 0.650(0.300-0.980) mg/kg and 0.043(0.012-0.089)mg/kg, which were
within the national health standards. Compared with the control group ((26.97 +/-
9.71)ug/g Cr), arsenic level in the patients' urine ((71.48 +/- 22.74)ug/g Cr)
increased significantly, the differences were significant (F = 90.38, P < 0.01).
Compared with the control group ((1.58 +/- 1.07)ug/g), arsenic level in the
patients' hair ((4.45 +/- 2.78) ug/g) increased significantly, the differences
were significant (F = 48.22, P < 0.01). The relative expression amount of the
median(quartile) for ERK2, JNK1 mRNA were 0.0667 (0.0378-0.1371) and 0.0013
(0.0009-0.0025), respectively. Compared with the control group 0.1744 (0.1009
0.1985) and 0.0022 (0.0017-0.0030) , only the decreases of ERK2, JNK1 mRNA
expression was significant (chi(2) = 15.10, 14.25, P < 0.01), and no significance
in the other index. ERK2 mRNA relative expression for mild, medium and severe
groups were separately 0.0818 (0.0408-0.1509) ,0.0582 (0.0154-0.1699) and 0.0588
(0.0399-0.1034) . Compared with the control group (0.1744 (0.1099-0.1985) ),
there was significant difference (Z = -2.89, -3.19, -2.67, P < 0.01). JNK1 mRNA
relative expression were 0.0012 (0.0007-0.001 57), 0.0019 (0.0011-0.0035), 0.0013
(0.0010-0.0026), respectively. Compared with the control group (0.0022 (0.0017
0.0030) ), significances were found in the mild groups (Z = -3.72, P < 0.01).
CONCLUSIONS: Arsenic could induce the changes of ERK2 and JNK1mRNA expression in
the MAPK path way in arseniasis patients.It suggests that the MAPK signaling
pathway take part in the occurrence and development process of arseniasis caused
by burning coal.
PMID- 24351558
TI - [Chronic combined effects of fluoride and arsenite on the Runx2 and downstream
related factors of bone metabolism in rats].
AB - OBJECTIVE: To observe the chronic combined effects of sodium fluoride and sodium
arsenite on the Runx2 and downstream related factors of bone metabolism in SD
rats. METHODS: SD rats were divided randomly into nine groups of 6 each by
factorial experimental design (half female and half male) , and supplied with the
different doses of fluoride, arsenite and fluoride plus arsenite containing in
deionized water (untreated control containing 0 mg/kg fluoride and 0 mg/kg
arsenite, and low-fluoride and high supplemented with 5 and 20 mg/kg fluoride,
and low-arsenite and high supplemented with 2.5 and 10 mg/kg arsenite, and low
fluoride plus low-arsenite, and low-fluoride plus high-arsenite, and high
fluoride plus low-arsenite, and high-fluoride plus high-arsenite, respectively) .
After 6 months exposure, the concentration of Runx2, matrix metallopeptidase 9
(MMP-9) ,Osterix, Receptor activator for nuclear factor-kappa beta ligand (RANKL)
were detected by enzyme-linked immunosorbent assay method, respectively. RESULTS:
There were no dental fluorosis found in the control group, low-arsenic group and
high-arsenic group. There were significant differences in the constituent ratio
of dental fluorosis among the rats from low-fluoride and high-fluoride (that is 5
rats out of 6 and 6 rats out of 6) compared with the control group (0 rat out of
6) (chi(2) = 8.57, 12.00, P < 0.05). The bone fluorine level increased with the
increase of fluoride dose, the groups without fluoride supply (control group, low
arsenite and high-arsenite group's geometric mean (minimum-maximum) were 0.005
(0.003-0.009), 0.006 (0.003-0.021), 0.003 (0.002-0.100) mg/g, respectively), low
fluorine groups (low-fluoride group, low-fluoride plus low-arsenite, and low
fluoride plus high-arsenite group were 3.395 (2.416-5.871), 3.809 (1.471-7.799),
1.471 (1.473-6.732)mg/g, respectively) , the high-fluorine groups (high-fluoride,
high-fluoride plus low-arsenite, and high-fluoride plus high-arsenite group were
70.086 (46.183-131.927), 69.925 (40.503-96.183), 40.503 (52.622-89.487) mg/g,
respectively) and the differences between groups was significant (P < 0.05). The
bone arsenic level increased with the increase of arsenite dose. The low-arsenic
groups (low-arsenite group, low-arsenite plus low-fluoride, and low-arsenite plus
high-fluoride group were 7.195 (5.060-9.860), 6.518 (2.960-12.130), 6.970 (3.400
9.730) ug/g, respectively), the high-arsenic groups (high-arsenite, high-arsenite
plus low-fluoride, and high-fluoride plus high-arsenite group's geometric
mean(minimum-maximum) were 8.823 (5.760-10.840), 9.470 (7.230-12.860), 8.321
(2.420-17.540) ug/g, respectively) were significantly higher than that in the
groups without arsenic supply (control group, low-fluoride and high-fluoride
group were 1.785 (0.300-3.750), 2.226 (1.410-3.980), 2.030 (1.040-3.850)ug/g,
respectively) (P < 0.05). There was no significant difference of the bone arsenic
concentration between low-arsenic and high arsenic group. There was significant
positive correlation between fluoride concentration and Runx2, MMP-9, Osterix,
RANKL level (the correlation coefficient was 0.647, 0.354, 0.582, 0.613 between
fluorine gavage concentration and protein level, the correlation coefficient was
0.559,0.387, 0.487, 0.525 between bone fluorine concentration and protein level,
respectively, P < 0.01). There was negative correlation between arsenite gavage
concentration with Runx2 level (r = -0.527, P < 0.05) and was no correlation
between arsenite gavage concentration with MMP-9, RANKL,Osterix level (P > 0.05).
There was interaction between fluoride and arsenite to Runx2, MMP-9,
RANKL,Osterix (F = 3.88, 15.66, 2.92, 6.42, respectively, P = 0.01, <0.01, 0.031,
<0.01, respectively). CONCLUSION: The combined effects of fluoride and arsenic on
the Runx2, MMP-9, RANKL, Osterix of bone metabolism showed antagonistic effects.
PMID- 24351559
TI - [The establishment of the arsenic poisoning rats model caused by corn flour baked
by high-arsenic coal].
AB - OBJECTIVE: To establish coal arsenic poisoning rat model by feeding the rats with
the corn powder baked by high arsenic coal as the main raw material. METHODS:
Fifty Wistar rats, healthy, were randomly divided into 5 groups according to the
figures of their weights, including control group, drinking arsenic poisoning
water group, low, medium and high arsenic contaminated grain group, 10 rats for
each.Rats in control group and drinking arsenic poisoning water group were fed
with standard feed without any arsenic containing. Rats in water group would
drink 100 mg/L As2O3 solution and the rats in arsenic grain groups would be fed
with the arsenic contaminated grain at the dose of 25, 50 and 100 mg/kg,
respectively. The duration would last for 3 months.General situation and weight
were observed. At the same time, the arsenic contents of urine, hair, liver and
kidney of the rats in each group were detected, as well as the histopathology
changes of liver and kidney, and the ultra structure of liver was observed.
RESULTS: The arsenic contents of urine (median(min-max)) of the rats in the
arsenic water group, low, medium and high arsenic grain groups were separately
3055.59 (722.43-6389.05), 635.96(367.85-1551.31), 1453.84 (593.27-5302.94) and
3101.11 (666.64-6858.61) ug/g Cr; while the arsenic contents of hair of the rats
in the above groups were separately (23.07 +/- 10.38), (8.87 +/- 3.31), (12.43 +/
6.65) and (25.68 +/- 7.16) ug/g; the arsenic contents of liver of the rats in
the above groups were separately (5.68 +/- 3.13), (2.64 +/- 1.52), (3.89 +/-
1.76) and (5.34 +/- 2.78) ug/g; and the arsenic contents of kidney were
separately (6.90 +/- 1.94), (3.48 +/- 1.96), (5.03 +/- 2.08) and (7.02 +/- 1.62)
ug/g; which were all significantly higher than those in the control group (86.70
(49.71-106.104) ug/g Cr,(1.28 +/- 0.37) ug/g, (1.01 +/- 0.34) ug/g and (1.82 +/-
1.09) ug/g, respectively). The difference showed significance (P < 0.05). Under
electron microscope detection, we observed the reduction of mitochondrial, the
blurred mitochondrial cristae, some disappeared ridges, the reduced rough
endoplasmic reticulum, and irregular uneven nuclear in the liver cells of rats in
arsenic contaminated grain group. The contents of aspartate transaminase (AST)
and total bile acid (TBA) in medium and high arsenic contaminated grain group
were respectively (196.17 +/- 46.18), (212.40 +/- 35.14) U/L and (11.74 +/-
4.07), (19.19 +/- 4.68)umol/L, which were higher than it in the control group
(separately (143.10 +/- 29.13) U/L and (6.23 +/- 2.95)umol/L). The contents of
glutathione-S-transferases(GST), gamma-glutamyltranspeptidase (GGT)and blood urea
nitrogen (BUN)in high arsenic contaminated grain group were separately (196.21 +/
47.38)U/L, (1.71 +/- 0.66)U/L, (9.54 +/- 1.95)mmol/L, which were higher than
that in the control group ((134.93 +/- 24.80 )U/L, (0.75 +/- 0.36)U/L, (7.67 +/-
1.02)mmol/L, respectively). The contents of cholinesterase (CHE) in low, medium
and high arsenic contaminated grain group were separately (259.90 +/- 52.71)U/L,
(263.44 +/- 66.06)U/L and (244.90 +/- 36.14)U/L, the contents of total
protein(TP) in rats of high arsenic contaminated grain group were (62.64 +/-
5.50)g/L, which was all lower than that in the control group ((448.33 +/-
59.67)U/L, (69.38 +/- 4.24)g/L, respectively). The contents of TBA in high
arsenic contaminated grain group ( (19.19 +/- 4.68) umol/L) was higher than that
in drinking water arsenic poisoning group ((15.15 +/- 2.64)umol/L). The
differences of the above indexes were all significant (P < 0.05). CONCLUSION: The
results showed the arsenic poisoning rat model produced by coal-burning were
successfully established.
PMID- 24351560
TI - [A cross-sectional study of the association of movement disorders, constipation
and sleep disturbances among elderly in China].
AB - OBJECTIVE: To investigate the current status and association between movement
disorders, constipation and sleep disturbances in the elderly population of
China. METHODS: A total of 42 353 subjects aged over 60 years old from Chinese
Chronic Non-communicable Disease & Risk Factor Surveillance (2010) was selected
in our study. The information on movement disorders, constipation and sleep
disturbances was collected by standardized questionnaire interview. The
prevalence and association of self-reported movement disorders, constipation and
sleep disturbances was measured according to different gender, age groups and
regions. RESULTS: The study was conducted among 42 353 old adults, including 21
893 males (51.7%) and 20 460 females (48.3%); 17 917 from urban areas (42.3%) and
24 436 from rural areas (57.7%); and the proportion of elderly from eastern,
central and western regions were 37.9% (16 031 subjects), 29.1% (12 345 subjects)
and 33.0% (13 977 subjects) respectively. After weighted complex analysis, the
data showed that among the elderly population over 60 years old in China, the
self-reported rates of movement disorders, constipation and sleep disturbances
were all age-related, rising up with the age increasing. The rates of 60-64 age
group were 2.8% (95%CI:1.9%-3.7%), 3.6% (95%CI:3.1%-4.1%) and 12.4% (95%CI:11.0%
13.8%);and in >= 80 age group, the rates were 13.2% (95%CI:10.2%-16.1%), 8.8%
(95%CI:7.1%-10.6%) and 19.1% (95%CI:16.3%-21.9%). The self-reported rate of
movement disorders was 5.7% (95%CI: 4.5%-7.0%); the prevalence of constipation
was 5.1% (95%CI: 4.4%-5.7%), which was higher among women (5.8%, 95%CI: 5.0%
6.6%) than it among men (4.3%, 95%CI: 3.7%-4.8%) (chi(2) = 23.40, P < 0.05), and
higher among subjects from urban areas (6.0%, 95%CI: 5.1%-7.0%) than from rural
areas (4.6%, 95%CI: 3.8%-5.4%) (chi(2) = 5.62, P < 0.05); the prevalence of self
reported sleep disturbances was 14.2% (95%CI: 12.7%-15.8%), higher in women
(17.4%, 95%CI: 15.4%-19.3%) than in men (11.0%, 95%CI: 9.7%-12.2%) (chi(2) =
172.05, P < 0.05); the prevalence of movement disorders in people with
constipation (16.3%, 95%CI: 12.7%-19.9%) was much higher than it in people
without constipation (5.2%, 95%CI: 4.0%-6.3%) (chi(2) = 242.73, P < 0.05); and
the prevalence of movement disorders in people with sleep disturbances (13.0%,
95%CI: 10.6%-15.4%) was much higher than it in people without sleep disturbances
(4.5%, 95%CI: 3.5%-5.5%) (chi(2) = 688.80, P < 0.05).Logistic regression analysis
showed that constipation and sleep disturbances would increase the risk of
movement disorders, with the OR (95%CI) at 2.93 (2.57-3.33) and 2.73 (2.48-3.02),
respectively. CONCLUSION: The present study showed that self-reported rates of
movement disorders, constipation and sleep disturbances all rose up with age
increasing in the elderly. The movement disorders was associated with
constipation and sleep disturbances.
PMID- 24351561
TI - [Survey on current status of cognitive function among Chinese elderly people].
AB - OBJECTIVE: To investigate the current status and distribution features of
cognitive function among the elderly population of China. METHODS: A total of 18
137 subjects aged over 60 years old from 2010 Chronic Non-communicable Disease &
Risk Factor Surveillance in China were selected in this study. Questionnaire was
used to collect the information about gender, age and health status. The Mini
Mental State Examination (MMSE) was adopted as an instrument to measure the
cognitive function of adult who had self-reported memory decline. After
performing complex weighted analysis, the current status of cognitive function
and the prevalence of cognitive disorder were compared by different genders, age
groups, urban/rural and education levels. RESULTS: Among the 18 086 subjects, the
median of MMSE sore was 23. The score was higher in males (25) than in females
(22) and it was higher in urban (25) than in rural area (22). The cognitive
function declined with age increasing. The group of people aging 60-64 years old
had the highest score (26), and the group of people aging >= 80 years old had the
lowest score (19). The MMSE score rose up with education level increasing, the
group of people with education level above middle school had the highest score
(28) and the group of illiterate people had the lowest score (20). The prevalence
of overall cognitive disorder was 10.12% (95%CI: 8.22%-12.02%). The female
prevalence (12.45%, 95%CI:9.95%-14.94%) was higher than male prevalence (7.68%,
95%CI:5.94%-9.43%). The group of people aged 60-64 years old had the lowest
prevalence (4.69%, 95%CI:3.40%-5.98%), and the people aged >= 80 years old had
the highest prevalence (22.43%, 95%CI:17.80%-27.05%). The prevalence increased
with age increasing (chi(2) = 320.02, P < 0.01). The prevalence of cognitive
disorder in illiterate group was 14.6% (95%CI:12.01%-17.23%), and it was
separately 6.92% (95%CI: 5.21%-8.64%) and 3.99% (95%CI: 2.58%-5.40%) in group of
people with education background of primary school and middle school. The
prevalence decreased with education levels increasing (chi(2) = 156.49, P <
0.01). Married or cohabiting elderly people had the lowest prevalence (8.51%,
95%CI: 6.58%-10.43%), lower than single ones (9.32%, 95%CI: 4.00%-14.64%) and
divorced ones (14.89%, 95%CI: 12.37%-17.50%). The prevalence of cognitive
disorder among rural population (12.16%, 95%CI: 9.51%-14.82%) was higher than it
among urban population (5.93%, 95%CI: 4.78%-7.07%). The prevalence in central
area (13.57%, 95%CI: 8.55%-18.58%) was higher than that in east (7.96%, 95%CI:
6.17%-9.74%) and west region (9.50%, 95%CI: 7.62%-11.38%) of China. The
difference was statistically significant (chi(2) = 54.55, 29.76, 8.81
respectively, P < 0.05). CONCLUSION: The prevalence of cognitive disorder among
the elderly people over 60 years old was age-related and varied by different
gender, marriage status, educational status and the regional distribution.
PMID- 24351562
TI - [Relationship between prevalent features of central obesity and clustering of
cardiometabolic diseases among Chinese elder people].
AB - OBJECTIVE: To study the relationship between prevalence of central obesity and
clustering of cardiometabolic diseases among Chinese elder people over 60 years
old. METHODS: A complex multistage stratified sampling survey on chronic diseases
was conducted in 162 surveillance points, 31 provinces, China in 2010 by China
CDC. The survey included face-to-face interview, physical measurement (body
height, weight, waist circumference (WC) and blood pressure) and laboratory test
(blood sugar, blood lipid and hemoglobin A1C), to collect the information about
the prevalence of the risk factors as smoking, drinking, diet and physical
activities and the prevalence of hypertension, diabetes and dyslipidemia. The
survey selected 19 966 subjects who were over 60 years old. Central obesity was
defined as WC >= 85 cm in males or >= 80 cm in females. The prevalence of central
obesity among the elder people over 60 years old in different districts and
populations was calculated; and the proportion of cardiometabolic diseases in
groups of different WC was then analyzed. RESULTS: The prevalence of central
obesity among elderly population over 60 years old was 48.6% (95%CI:46.1%-51.2%),
including 39.7% (95%CI:37.2%-42.2%) males and 57.3% (95%CI:54.5%-60.1%) females.
The proportion of females was higher than that of males (chi(2) = 474.63, P <
0.01). The higher the education level, the higher the prevalence of central
obesity among elderly men. There was no significant association among females.
The higher the family income, the higher the prevalence of central obesity. The
prevalence of central obesity was 59.2% in urban area, which was much higher than
that in rural area (43.5%) (chi(2) = 50.06, P < 0.01). The proportion of
hypertension, diabetes and clustering of cardiometabolic disease was separately
18.8% (95%CI:16.1%-21.5%) , 66.2% (95%CI:63.0%-69.4%) and 47.5% (95%CI:44.1%
50.8%) among elderly men with WC between 85 and 89 cm, and separately 24.0%
(95%CI:21.2%-26.8%), 78.2% (95%CI:75.6%-80.8%) and 64.0% (95%CI:60.3%-67.6%)
among elderly men with WC >= 90 cm; which were both higher than those among
elderly men with WC < 85 cm (separately 13.4% (95%CI:11.5%-15.3%) , 58.3% (
95%CI:55.5%-60.1%) and 30.8% (95%CI:28.7%-32.9%) ). The proportion of
hypertension, diabetes and clustering of cardiometabolic disease was 20.1%
(95%CI:17.4%-22.7%) , 68.6% (95%CI:65.5%-71.8%) and 48.1% (95%CI:44.6%-51.6%)
among elderly women with WC between 80 and 84 cm, and separately 31.7%
(95%CI:28.9%-34.4%) , 81.0% (95%CI:78.5%-83.5%) and 61.8% (95%CI:58.9%-64.8%)
among elderly women with WC >= 85 cm; which were both higher than those among
elderly women with WC < 80 cm (separately 12.8% (95%CI:10.8%-14.8%) , 60.1%
(95%CI:57.1%-63.0%) and 30.4% (95%CI:27.3%-33.5%)). CONCLUSION: Nearly half of
the Chinese elder people were central obese. The proportion of cardiometabolic
diseases among central obesity was significantly higher than that among non-obese
population. We should pay more concern about them in the future prevention and
control of chronic diseases.
PMID- 24351563
TI - [Study on risk factors and behavior features related to chronic diseases among
adults in Shanghai].
AB - OBJECTIVE: To investigate the risk factors and behavior features related to
chronic diseases among adults in Shanghai. METHODS: A total of 15 516 subjects
aged over 18 years old were selected from the investigation project on chronic
diseases and relevant risk factors in Shanghai in 2010. Questionnaire were used
to investigate the general information of the subjects, such as behavior features
as smoking, drinking, diet, physical activity as well as the prevalence and
control of chronic diseases as hypertension and diabetes. The physical
examination included height, weight, waist circumference, blood pressure, blood
glucose and blood lipids. RESULTS: Being preprocessed by complex weighting
method, the data showed that the overweight rate of Shanghai adults aged above 18
was 32.4% (5288), separately 32.2% (2506) and 32.5% (2782) (chi(2) = 0.10, P =
0.844) in urban and rural areas; the obesity rate was 8.8% (1538), separately
8.7% (738) and 8.8% (800) (chi(2) = 0.06, P = 0.901) in urban and rural areas.
The overweight rate was separately 36.0% (2888) in males and 28.6% (2400) in
females (chi(2) = 96.61, P < 0.01); while the obesity rate was separately 8.7%
(745) in males and 8.9% (793) in females (chi(2) = 0.06, P = 0.851). Abdominal
obesity rate was 44.3% (7419), separately 47.8% (3892) in males and 40.6% (3527)
in females (chi(2) = 81.23, P < 0.01), 46.5% (3703) in urban areas and 42.6%
(3716) in rural areas (chi(2) = 24.37, P = 0.069). Current smoking rate was 25.0%
(3813), separately 48.4% (3722) and 1.2% (91) in males and females (chi(2) =
4572.06, P < 0.01); 23.6% (1609) and 26.0% (2204) in urban and rural areas
(chi(2) = 11.92, P = 0.018). The regular smoking rate was 22.1% (3402). The rate
of having the habit of drinking at least once a month in males was 39.5% (3102),
separately 35.1% (1262) and 42.7% (1840) in urban and rural areas (chi(2) =
45.98, P = 0.012). The rate of drinking almost every day was 16.3% (1380), and
the percentage of excessive alcohol consumption was 28.9% (2483). The percentage
in group of subjects aging between 45-59 years old was 38.5% (1191), which was
higher than that in any other groups (22.8% (641) in group aging 18-44 years old
and 22.9% (651) in group aging >= 60 years old) (chi(2) = 241.38, P < 0.01). The
percentage of over-drinking in rural area was higher than that in urban area,
which was 33.5% (1578) and 22.8% (905) respectively (chi(2) = 117.12, P < 0.01).
The percentage of once over-drinking was 11.3% (903). It was higher in group
aging between 45-49 years old (15.3% (461)) than in other groups (9.0% (222) in
group aging 18-44 years old and 8.2% (220) in group aging >= 60 years old)
(chi(2) = 78.21, P < 0.01). It was also higher in rural area (13.5% (605)) than
in urban area (8.3% (298)) (chi(2) = 51.74, P < 0.01). There were 75.0% (11 993)
of the Shanghai adults never took physical activity. And the most important
problems in dietary habit were insufficient intake of dairy products (98.0%, 15
218), vegetables (53.0%, 7864) and fruits (84.6%, 13 372), excess consumption of
sodium (52.0%, 8257) and oil (51.7%, 7884). CONCLUSION: The risk factors of
chronic diseases were highly prevalent in Shanghai. The prevalence of risk
factors as overweight or obesity, lack of physical activity, smoking, over
drinking and unhealthy dietary habits were higher among adults living in suburban
areas than those living in urban areas; the prevalence was also higher among the
young adults than that among the elderly people, higher among males than that
among females.
PMID- 24351564
TI - [Trend in meat consumption patterns among Chinese children in nine
provinces(autonomous region) aged 6 to 17 years between 1991 and 2011].
AB - OBJECTIVE: To examine the trend in meat consumption patterns between 1991 and
2011 in Chinese children in nine provinces(autonomous region) aged 6 to 17 years.
METHODS: A multistage, random cluster sampling process was used to investigate
2720, 2702, 2525, 2405, 1509, 1238, 1085, and 936 children and adolescents aged 6
17 years in 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011 respectively in 9
provinces (autonomous region) in China. Their consecutive 3 d 24 h dietary recall
data were analyzed to compare meat intake pattern in children and adolescents
with different characteristics and different years. RESULTS: The consumption rate
increased from 60.9% (1657/2720) in 1991 to 87.2% (816/936) in 2011 for livestock
meat (chi(2) = 458.23, P < 0.01), from 9.4% (257/2720) to 33.3% (312/936) for
poultry (chi(2) = 446.07, P < 0.01) and from 27.3% (743/2720) to 40.6% (380/936)
for seafood (chi(2) = 89.89, P < 0.01). The median of total meat intake increased
from 47.4 g/d in 1991 to 100.0 g/d in 2011 (chi(2) = 516.77, P < 0.01), poultry
intake from 33.3 g/d to 60.0 g/d (chi(2) = 420.13, P < 0.01), pork intake from
26.7 g/d to 50.0 g/d (chi(2) = 380.50, P < 0.01). The percentage of children
whose livestock meat and poultry intakes higher than the recommended amount
increased from 32.9% (896/2720) in 1991 to 59.8% (560/936) in 2011 (chi(2) =
392.97, P < 0.01); the percentage of children whose seafood intakes meeting the
recommended amount increased from 6.9% (187/2720) in 1991 to 8.8% (82/936) in
2011 (chi(2) = 21.52, P < 0.01). The consumption rates of livestock meat in urban
and rural children increased from 81.2% (536/660) and 54.4% (1121/2060) in 1991
to 94.7% (234/247) (chi(2) = 38.34, P < 0.01) and 84.5% (582/689) (chi(2) =
429.26, P < 0.01) in 2011. The intakes of livestock meat in rural children
increased from 16.7 g/d in 1991 to 56.7 g/d in 2011 (chi(2) = 472.46, P < 0.01).
CONCLUSION: The overall pattern of meat consumption in Chinese children in nine
provinces(autonomous region) was unreasonable between 1991 and 2011. There was a
significant improvement in meat consumption in rural children over time.
PMID- 24351565
TI - [Concentration level and characteristics of indoor particle matter <= 2.5 um in
aerodynamic diameter under extreme weather condition in Beijing winter in 2013].
AB - OBJECTIVE: To study the concentration level and characteristics of indoor
particle matter <= 2.5 um in aerodynamic diameter (PM2.5) under extreme weather
condition. METHODS: During the period of haze in January 2013 and the fireworks
and firecracker setting off in the Spring Festival of February 2013, three
monitoring sites located indoor and outdoor were respectively selected by Beijing
CDC, considering the vertical and horizontal distance, windows tightness and
human activity indoor. PM2.5 samples were collected by filters and measured by
laboratory weight method. At the same time, the meteorological data was also
collected. RESULTS: The median (quartiles) of overall concentration level of
indoor PM2.5 was 87.76 ug/m(3) (52.05-174.48 ug/m(3)) and was lower than that of
outdoor PM2.5 (128.79 ug/m(3), 95.14-221.88 ug/m(3); Z = -4.13, P < 0.01). The
concentration of three indoor monitoring sites was different (chi(2) = 23.09, P <
0.01). The PM2.5 concentrations of monitoring point B in poor sealing window was
the highest (94.05 ug/m(3); 63.46-189.17 ug/m(3)) and point C in sealed and less
human activity, which was the lowest (77.89 ug/m(3), 51.19-144.40 ug/m(3)). The
concentration level of indoor PM2.5 in the haze period (273.22 ug/m(3), 223.44
308.47 ug/m(3)) was higher than the overall concentration level of indoor PM2.5
(Z = -5.20, P < 0.01). The concentration level of indoor PM2.5 in the fireworks
and firecracker period (167.90 ug/m(3), 129.15-187.90 ug/m(3)) was higher than
that in the Spring Festival period (7 days, 72.76 ug/m(3), 36.97-145.30 ug/m(3),
Z = -2.34, P < 0.05) and the overall concentration level of indoor PM2.5 (Z =
1.98, P < 0.05); however, it was lower than the concentration level of indoor
PM2.5 in the haze period (Z = -3.43, P < 0.01). The I/O ratio (indoor
concentration/outdoor concentration) was all less than 1.00 except 4, which was
between 1.00-1.09. The mean I/O ratio in monitoring site B, monitoring site A and
monitoring site C was 0.69 +/- 0.21, 0.64 +/- 0.23 and 0.58 +/- 0.18,
respectively, show significant bias (F = 22.85, P < 0.01). During the period of
haze, the fireworks and firecracker and fine weather (when ambient PM2.5
concentration was lower than the standard value of 75 ug/m(3)), the mean I/O
ratio was 0.87 +/- 0.14, 0.68 +/- 0.08 and 0.51 +/- 0.18, respectively, showing
significant bias (F = 29.88, P < 0.05). Under conditions of snow and high wind
speed ( >= 3.4 m/s), PM2.5 concentration decreased to the valley point. The
valley value of I/O ratio only occurred after several days of high windy weather.
Moreover, the PM2.5 concentration level of indoor air showed a delayed 1-2 days
after the haze weakened or disappeared. CONCLUSION: Mass concentration of indoor
PM2.5 increased significantly with increases of outdoor concentration. Haze and
setting off fireworks/firecracker could lead to a serious decline of indoor air
quality (IAQ), and the improvement of IAQ was lagging behind the outdoor changes.
PMID- 24351566
TI - [Preliminary study of source apportionment of PM10 and PM2.5 in three cities of
China during spring].
AB - OBJECTIVE: To study source apportionment of atmospheric PM10 (particle matter <=
10 um in aerodynamic diameter) and PM2.5 (particle matter <= 2.5 um in
aerodynamic diameter) in Beijing,Urumqi and Qingdao, China. METHODS: The
atmospheric particle samples of PM10 and PM2.5 collected from Beijing between May
17th and June 18th, 2005, from Urumqi between April 20th and June 1st, 2006 and
from Qingdao between April 4th and May 15th, 2005, were detected to trace the
source apportionment by factor analysis and enrichment factor methods. RESULTS:
In Beijing, the source apportionment results derived from factor analysis model
for PM10 were construction dust and soil sand dust (contributing rate of variance
at 45.35%), industry dust, coal-combusted smoke and vehicle emissions
(contributing rate at 31.83%), and biomass burning dust (13.57%). The main
pollution element was Pb, while the content (median (minimum value-maximum
value)was 0.216 (0.040-0.795) ug/m(3)) . As for PM2.5, the sources were
construction dust and soil sand dust (38.86%), industry dust, coal-combusted
smoke and vehicle emissions (25.73%), biomass burning dust (13.10%) and burning
oil dust (11.92%). The main pollution element was Zn (0.365(0.126-0.808)
ug/m(3)).In Urumqi, source apportionment results for PM10 were soil sand dust and
coal-combusted dust(49.75%), industry dust, vehicle emissions and secondary
particles dust (30.65%). The main characteristic pollution element was Cd
(0.463(0.033-1.351) ng/m(3)). As for PM2.5, the sources were soil sand dust and
coal-combusted dust (43.26%), secondary particles dust (22.29%), industry dust
and vehicle emissions (20.50%). The main characteristic pollution element was As
(14.599 (1.696-36.741) ug/m(3)).In Qingdao, source apportionment results for PM10
were construction dust (30.91%), vehicle emissions and industry dust (29.65%) and
secondary particles dust (28.99%). The main characteristic pollution element was
Pb (64.071 (5.846-346.831) ug/m(3)). As for PM2.5, the sources were secondary
particles dust, industry dust and vehicle emissions (49.82%) and construction
dust (33.71%). The main characteristic pollution element was Pb(57.340 (5.004
241.559) ug/m(3)).Enrichment factors of Zn, Pb, As and Cd in PM2.5 were higher
than those in PM10 both in Beijing and Urumqi. CONCLUSION: The major sources of
the atmospheric particles PM10 and PM2.5 in Beijing were cement dust from
construction sites and sand dust from soil; while the major sources of those in
Urumqi were pollution by smoke and sand dust from burning coal. The major sources
of the atmospheric particles PM10 in Qingdao were cement dust from construction
sites; however, the major sources of PM2.5 there were secondary particles dust,
industry dust and vehicle emissions. According to our study, the heavy metal
elements were likely to gather in PM2.5.
PMID- 24351567
TI - [Acceptability status of early antiretroviral therapy among HIV-positive men who
have sex with men].
AB - OBJECTIVE: To assess the acceptability and influence factors of early
antiretroviral therapy (ART) among HIV-positive men who have sex with men (MSM) .
METHODS: From June to August 2012, through convenience sampling, HIV-positive MSM
who were willing to cooperate with the survey were selected from the Hangzhou and
Ningbo AIDS prevention and control database. A total of 280 HIV-positive MSM who
did not receive ART participated in the study.Using self-designed questionnaire,
general demographic information, awareness of AIDS knowledge, sexual behavior,
use of condom, current physical condition, awareness and attitude towards early
ART were investigated.Excluding 60 HIV-infected MSM whose CD4(+)T count didn't
meet the inclusion criteria, a total of 220 subjects were included in the
analysis. Chi-square was used to compare the difference of early ART acceptance
among subjects with different characteristics.Non-conditional logistic regression
was used to analyze the influence factors of the acceptability of early ART.
RESULTS: The acceptance rate of early ART among HIV-infected MSM was 62.7%
(138/220). Delaying the disease development, preventing partners from infection,
not worrying others to suspect them of having HIV, and partners unknowing the HIV
infected status were the factors which had a relatively higher acceptance rate of
early ART. Correspondingly, the acceptance rate was 68.8% (130/189), 68.7%
(103/150), 78.4% (69/88) and 72.5% (74/102) respectively and the acceptance rate
among subjects with opposite opinions or characteristics was 24.1% (7/29) , 50.0%
(30/60), 52.7% (68/129) and 45.8% (58/107) respectively (chi-square values were
21.46, 6.43, 14.84 7.55, all P values <0.05).Logistic regression analysis showed
that delaying the disease development (OR = 11.50, 95%CI:3.29-40.22) and
preventing partners from infection (OR = 3.72, 95%CI:1.53-9.03) were inclined to
the acceptance of early ATR.While concerning others' suspection of them having
HIV (OR = 0.19, 95%CI:0.08-0.48) and partners knowing the HIV-infected status
were inclined to unacceptance of ART(OR = 0.31, 95%CI:0.13-0.70). CONCLUSION: The
acceptability of early ART among HIV-positive MSM is high. The recognition of
early ART and concern of privacy leak are the major influence factors which can
stimulate the acceptance of early ART.
PMID- 24351568
TI - [Evidence-based study of chromate exposed workers' health surveillance indexes].
AB - OBJECTIVE: The health surveillance proposal for chromate exposed workers was
provided and analyzed on the evidence-based study and then to be improved.
METHOD: Firstly, the related literatures were searched about liver damage,
micronuclei, urinary chromium and hexavalent chromium exposure in Evidence Based
Medicine Reviews such as Cochran library, OVID Medline, Web of knowledge in
December 2011; and then, these literatures were reviewed in according to
inclusion and exclusion criteria; 22 articles totally were retrieved, evaluated
and classified in according to the grading standard by Oxford Centre for Evidence
based Medicine.Finally, field epidemiological investigation was further adopted
to confirm the efficiency and feasibility of this proposal, combined with cost
effectiveness analysis:the ratio of total cost divided survival years was used to
express the cost-effectiveness. RESULT: Only the glutamic pyruvic transaminase
test could not reflect liver damage caused by chromate exposure well; Urinary
chromium correlated well with the index reflecting body damage caused by chromate
exposure; Binucleated cells micronucleus index in peripheral blood lymphocyte
could reflect the genetic damage caused by chromate exposure. As for health
economic evaluation of chromate lung cancer, the value of cost/effectiveness was
Y42 321.61 per year that was far below the value of common people (Y252 868.97
per year) . CONCLUSION: It was suggested that serum glutamic pyruvic transaminase
test should be replaced by liver function test, urinary chromium should be
classified as a compulsory index and binucleated cells micronucleus index in
peripheral blood lymphocyte should be supplied as a recommended index.
PMID- 24351569
TI - Optimal force for maxillary protraction facemask therapy in the early treatment
of class III malocclusion.
AB - BACKGROUND: The facemask is used to treat early class III malocclusion, in
combination with expansion therapy. There is a great deal of controversy in
literature regarding the effectiveness of protraction facemask treatment as
studies report results anywhere from considerable changes to lack of any
maxillary improvement. This controversy may be due to the fact that the process
of placing the orthopaedic facemask on patients has, in part, been done
empirically, without the use of literature containing the clinical parameters for
facemask placement for maxillary protraction. OBJECTIVE: To determine the optimal
magnitude, duration, and direction that should be used in maxillary protraction
facemask therapy. SEARCH METHODS: A systematic search was carried out in the
following databases: Medline, Google Scholar, Embase, Cochrane, Lilacs, Scielo,
with no restriction placed on the year of publication, in English and Spanish,
using MeSH terms and free-text terms. SELECTION CRITERIA: Clinical trials,
systematic reviews, meta-analysis, cohort studies, case-control studies, and
cross-sectional studies were included, whereas literature reviews, case reports,
case series, symposiums, compendiums, pilot studies, and expert opinions were
excluded. DATA COLLECTION AND ANALYSIS: Data selection and extraction were
blinded and performed independently, and the methodology was evaluated using
various scales. RESULTS: A total of 223 articles were found. After eliminating
repeated articles and those that did not meet the selection criteria, 14 remained
for analysis. Regarding magnitude, there were values ranging from 180 to 800g per
side; there were force vector direction values between 20 and 30 degrees below
the occlusal plane or parallel to the occlusal plane; and a duration ranging from
10 to 24 hours of use per day. CONCLUSIONS: There is no scientific evidence that
would allow for the definition of adequate parameters for force magnitude,
direction, and duration for maxillary protraction facemask treatment in class III
patients.
PMID- 24351570
TI - Angle-resolved photoemission spectroscopy observation of anomalous electronic
states in EuFe2As(2-x)P(x).
AB - We used angle-resolved photoemission spectroscopy to investigate the electronic
structure and the Fermi surface of EuFe2As2, EuFe2As1.4P0.6 and EuFe2P2. We
observed doubled core level peaks associated with the pnictide atoms. Using K
atoms evaporated at the surface to affect the surface quality, we show that one
component of these doubled peaks is related to a surface state. Nevertheless,
strong electronic dispersion along the c-axis, especially pronounced in EuFe2P2,
is observed for at least one band, thus indicating that the Fe states, albeit
probably affected at the surface, do not form pure two-dimensional surface
states. We determine the evolution of the Fermi surface as a function of the P
content and reveal that the hole Fermi surface pockets enlarge with increasing P
content. We also show that the spectral weight near the Fermi level of EuFe2P2 is
reduced as compared to that of EuFe2As2 and EuFe2As1.4P0.6. Finally, we identify
the electronic states associated with the Eu(2+) f states and show an anomalous
jump in EuFe2P2.
PMID- 24351571
TI - Congenital hereditary endothelial dystrophy caused by SLC4A11 mutations
progresses to Harboyan syndrome.
AB - PURPOSE: Homozygous mutations in SLC4A11 cause 2 rare recessive conditions:
congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone,
and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing
loss. In addition, adult-onset Fuchs endothelial corneal dystrophy (FECD) is
associated with dominant mutations in SLC4A11. In this report, we investigate
whether patients with CHED go on to develop hearing loss and whether their
parents, who are carriers of an SLC4A11 mutation, show signs of having FECD.
METHODS: Patients with CHED were screened for mutations in the SLC4A11 gene and
underwent audiometric testing. The patients and their parents underwent a
clinical examination and specular microscopy. RESULTS: Molecular analyses
confirmed SLC4A11 mutations in 4 affected individuals from 3 families. All the
patients were found to have varying degrees of sensorineural hearing loss at a
higher frequency range. Guttate lesions were seen in 2 of the 4 parents who were
available for examination. CONCLUSIONS: Our observations suggest that CHED caused
by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity
of this may vary considerably. Patients with CHED should therefore be monitored
for progressive hearing loss. We could not determine conclusively whether the
parents of the patients with CHED were at increased risk of developing late-onset
FECD.
PMID- 24351572
TI - Comparison of efficacy and ocular surface toxicity of topical preservative-free
methylprednisolone and preserved prednisolone in the treatment of acute anterior
uveitis.
AB - PURPOSE: The aim of this study was to compare the antiinflammatory effect and
ocular surface toxicity of topical nonpreserved methylprednisolone sodium
succinate 1% and preserved prednisolone acetate suspension 1% for the management
of acute anterior uveitis (AAU). METHODS: In this prospective, randomized,
investigator-masked, comparative clinical trial, patients with mild-to-moderate
noninfectious AAU were assigned randomly to receive either hourly nonpreserved
methylprednisolone 1% (group A) or preserved prednisolone 1% (group B) eye drops
followed by a 2-week tapering regimen. Anterior chamber cells and flare were
clinically evaluated for the objective comparison of the antiinflammatory effect.
The main outcome measure was the percentage of patients with a resolution of
inflammation (anterior chamber cells <1+) on day 14. Ocular surface toxicity was
assessed by means of the corneal fluorescein staining score, tear breakup time,
Schirmer I test, and questionnaire-based grading of ocular discomfort parameters.
RESULTS: Seventy-two eyes of 68 patients were studied, of which 38 eyes were
enrolled in group A and 34 eyes were enrolled in group B. On day 14, 76.3% of the
patients in group A had resolution of inflammation compared with 70.6% of the
patients in group B, proving noninferiority (chi = 0.303, P = 0.582). The mean
anterior chamber cell grade reduction for patients in group A was similar to that
in group B (2.52 vs. 2.86, respectively; P = 0.92). Group A patients showed
significantly lower corneal fluorescein staining scores (P < 0.001) and reported
milder subjective ocular discomfort (0.55 vs. 1.43, P = 0.01) as compared with
group B. CONCLUSIONS: Both preparations demonstrated equal antiinflammatory
effects for the treatment of AAU. Nonpreserved methylprednisolone eye drops
exhibited a significantly lower ocular surface toxicity profile and milder
subjective discomfort when compared with that exhibited by preserved
prednisolone.
PMID- 24351573
TI - Oral liquid formulation of levothyroxine is stable in breakfast beverages and may
improve thyroid patient compliance.
AB - Patients on treatment with levothyroxine (T4) are informed to take this drug in
the morning, at least 30 min before having breakfast. A significant decrease of
T4 absorption was reported, in fact, when T4 solid formulations are taken with
food or coffee. According to preliminary clinical study reports, administration
of T4 oral solution appears to be less sensitive to the effect of breakfast
beverages on oral bioavailability. In the present study, stability of T4 oral
solution added to breakfast beverages was investigated. A 1 mL ampoule of single
dose Tirosint(r) oral solution (IBSA Farmaceutici Italia, Lodi, Italy) was poured
into defined volumes of milk, tea, coffee, and coffee with milk warmed at 50
degrees C, as well as in orange juice at room temperature. Samples were
sequentially collected up to 20 min and analyzed by validated liquid
chromatography-tandem mass spectrometry (LC-MS/MS) methods. The results of the
study demonstrated that T4 is stable in all beverages after 20 min incubation.
Demonstration of T4 stability is a prerequisite for a thorough evaluation of the
effect of breakfast beverages on the bioavailability of T4 given as oral solution
and for a better understanding of the reasons underlying a decreased T4
bioavailability administered as solid formulations.
PMID- 24351574
TI - Mathematical model to predict skin concentration after topical application of
drugs.
AB - Skin permeation experiments have been broadly done since 1970s to 1980s as an
evaluation method for transdermal drug delivery systems. In topically applied
drug and cosmetic formulations, skin concentration of chemical compounds is more
important than their skin permeations, because primary target site of the
chemical compounds is skin surface or skin tissues. Furthermore, the direct
pharmacological reaction of a metabolically stable drug that binds with specific
receptors of known expression levels in an organ can be determined by Hill's
equation. Nevertheless, little investigation was carried out on the test method
of skin concentration after topically application of chemical compounds. Recently
we investigated an estimating method of skin concentration of the chemical
compounds from their skin permeation profiles. In the study, we took care of
"3Rs" issues for animal experiments. We have proposed an equation which was
capable to estimate animal skin concentration from permeation profile through the
artificial membrane (silicone membrane) and animal skin. This new approach may
allow the skin concentration of a drug to be predicted using Fick's second law of
diffusion. The silicone membrane was found to be useful as an alternative
membrane to animal skin for predicting skin concentration of chemical compounds,
because an extremely excellent extrapolation to animal skin concentration was
attained by calculation using the silicone membrane permeation data. In this
chapter, we aimed to establish an accurate and convenient method for predicting
the concentration profiles of drugs in the skin based on the skin permeation
parameters of topically active drugs derived from steady-state skin permeation
experiments.
PMID- 24351575
TI - Effects of organic selenium on lead-induced impairments of spatial learning and
memory as well as synaptic structural plasticity in rats.
AB - To study the effect of organic Se on spatial learning and memory deficits induced
by Pb exposure at different developmental stages, and its relationship with
alterations of synaptic structural plasticity, postnatal rat pups were randomly
divided into five groups: Control; Pb (Weaned pups were exposed to Pb at
postnatal day (PND) 21-42); Pb-Se (Weaned pups were exposed to Se at PND 43-63
after Pb exposure); maternal Pb (mPb) (Parents were exposed to Pb from 3 weeks
before mating to the weaning of pups); mPb-Se (Parents were exposed to Pb and
weaned pups were exposed to Se at PND 43-63). The spatial learning and memory of
rat pups was measured by Morris water maze (MWM) on PND 63. We found that rat
pups in Pb-Se group performed significantly better than those in Pb group
(p<0.05). However, there was no significant difference in the ability of spatial
learning and memory between the groups of mPb and mPb-Se (p>0.05). We also found
that, before MWM, the numbers of neurons and synapses significantly decreased in
mPb group, but not in Pb group. After MWM, the number of synapses, the thickness
of postsynaptic density (PSD), the length of synaptic active zone and the
synaptic curvature increased significantly in Pb-Se and mPb-Se group; while the
width of synaptic cleft decreased significantly (p<0.05), compared to Pb group
and mPb group, respectively. However, the number of synapses in mPb-Se group was
still significantly lower than that in the control group (p<0.05). Our data
demonstrated that organic Se had protective effects on the impairments of spatial
learning and memory as well as synaptic structural plasticity induced by Pb
exposure in rats after weaning, but not by the maternal Pb exposure which reduced
the numbers of neurons and synapses in the early neural development.
PMID- 24351576
TI - Persistent trigeminal artery: in situ thrombosis and associated perforating
vessel infarction.
AB - We report a patient with progressive brainstem infarction despite medical
therapy. The patient was transferred to our institution for potential angioplasty
of basilar stenosis. Imaging review demonstrated persistent trigeminal artery in
situ thrombosis and associated perforating vessel infarction. Persistent
trigeminal arteries are commonly associated with an atretic basilar artery and
interventional treatment can result in significant morbidity and mortality.
PMID- 24351579
TI - Basic research.
PMID- 24351577
TI - Delayed presentation of prolonged hyperinsulinaemic hypoglycaemia in a preterm
small-for-gestational age neonate.
AB - Hyperinsulinaemic hypoglycaemia in small-for-gestational age infants usually
presents in the first two postnatal days. We present a preterm, small-for
gestational age infant who had hyperinsulinaemic hypoglycaemia on day 13 of life.
A female twin infant weighing 1390 g was born at 32(+6) weeks of gestation. Her
glycaemic profile was normal till day 13 of life, after which she was noted to be
lethargic and hypoglycaemic and had hyperinsulinism, hypoketonaemia and
hypofattyacidaemia, requiring high glucose infusion rate to maintain
normoglycaemia, while negative for septic markers and metabolic screen.
Initially, there was no response to diazoxide and the genetic studies for ABCC8
and KCNJ11 gene mutations were negative. Delayed response to diazoxide was
followed by complete resolution of hypoglycaemia in 5 months. This case
highlights the importance of glucose monitoring in small-for-date infants for
hypoglycaemia till they achieve full feeds and gain weight. Early recognition and
appropriate management of hypoglycaemia in this group of infants have important
implications for neurodevelopmental outcome.
PMID- 24351580
TI - Spinal cord injury facts and figures at a glance.
PMID- 24351578
TI - The use of diaries in psychological recovery from intensive care.
AB - Intensive care patients frequently experience memory loss, nightmares, and
delusional memories and some may develop symptoms of anxiety, depression, and
post-traumatic stress. The use of diaries is emerging as a putative tool to 'fill
the memory gaps' and promote psychological recovery. In this review, we
critically analyze the available literature regarding the use and impact of
diaries for intensive care patients specifically to examine the impact of diaries
on intensive care patients' recovery. Diversity of practice in regard to the
structure, content, and process elements of diaries for intensive care patients
exists and emphasizes the lack of an underpinning psychological
conceptualization. The use of diaries as an intervention to aid psychological
recovery in intensive care patients has been examined in 11 studies, including
two randomized controlled trials. Inconsistencies exist in sample
characteristics, study outcomes, study methods, and the diary intervention
itself, limiting the amount of comparison that is possible between studies.
Measurement of the impact of the diary intervention on patient outcomes has been
limited in both scope and time frame. Furthermore, an underpinning
conceptualization or rationale for diaries as an intervention has not been
articulated or tested. Given these significant limitations, although findings
tend to be positive, implementation as routine clinical practice should not occur
until a body of evidence is developed to inform methodological considerations and
confirm proposed benefits.
PMID- 24351581
TI - Group behavior therapy versus individual behavior therapy for healthy dieting and
weight control management in overweight and obese women living in rural
community.
AB - SUMMARY: OBJECTIVE: To compare group behavior therapy with individual behavior
therapy for promoting healthy dieting behavior and weight control in overweight
and obese women in rural community. METHODS: This parallel group, open labeled,
randomized non-inferiority trial was conducted from March 2005 to April 2006. A
total of 132 overweight and obese women with a mean (S.D.) age of 38.4 (7.9)
years and body mass index (BMI) of 28.9 (2.9) kg/m(2) were randomly assigned to
receive either group behavior therapy (n = 65) or individual behavior therapy (n
= 67). Five intervention sessions were provided biweekly during the 3-month
period. Assessments were conducted at months 3, 6, and 12. Primary outcome was
mean percentage weight loss at month 6. Other outcomes included anthropometric
outcomes, dietary intake, healthy dieting behavior, intention, perceived
behavioral control, attitude, and subjective norm. RESULTS: Mean percentage
weight loss at month 6 of group behavior therapy was comparable to individual
behavior therapy (5.9% (95%CI: 4.5-7.3) versus 5.4% (95%CI: 4.0-6.7)); P = 0.027
for non-inferiority at one sided 0.05 level of significance. Other outcomes were
remarkably similar between the two study groups. Attitude, subjective norm, and
perceived behavioral control improved slightly; whereas, intention, healthy
dieting behavior, and dietary intake improved significantly after interventions.
High intention and perceived behavioral control was related to greater weight
loss. At 1 year, 73% of participants either lost or maintained their weight.
Anthropometric outcomes and healthy dieting behavior were significantly better
than baseline. CONCLUSIONS: Group behavior therapy was not inferior to individual
behavior therapy, and it should be used as the first line mode of behavior
therapy for weight control management in a rural community.
PMID- 24351582
TI - Uncoupling protein 1 contributes to fat-reducing effect of leptin.
AB - SUMMARY: Leptin is proposed to reduce body fat by increasing energy expenditure,
in addition to decreasing food intake, through the activation of brown adipose
tissue (BAT) thermogenesis. To confirm this, we investigated the effects of
leptin on whole body energy expenditure, BAT functions and adiposity in wild-type
(WT) mice, and compared with those in mice deficient in uncoupling protein 1
(UCP1), a key molecule for BAT thermogenesis. Chronic hyperleptinemia induced by
adenovirus gene transfer reduced food intake in both WT and UCP1-KO mice. WT mice
with hyperleptinemia, compared to pair-fed controls, showed increased oxygen
consumption, elevated UCP1 expression in BAT, ectopic UCP1 induction in white
adipose tissue (WAT), and reduced body fat content. These effects of chronic
hyperleptinemia were not observed in UCP1-KO mice. It was concluded that the fat
reducing effect of leptin is due to not only decreased food intake, but also
increased UCP1-dependent energy expenditure.:
PMID- 24351583
TI - Maternal predictors of birthweight: The importance of weight gain during
pregnancy.
AB - SUMMARY: OBJECTIVE: To investigate the importance of maternal weight gain during
pregnancy as a predictor of birthweight. SUBJECTS: Two thousand and forty-six
mother-infant pairs were recruited in 1984-1985 from 14 maternity units from the
Stockholm Pregnancy and Weight Development Study. METHODS: Weight gain during
pregnancy (WGP), smoking, pre-pregnancy BMI, gestational diabetes, hypertension,
parity, marital status, age, and sex of the child were investigated as predictors
of birthweight by multiple regression analysis. WGP was analysed as a continuous
and categorical variable, with the latter defined according to the Institute of
Medicine (IOM) recommendations as inadequate (n = 501), adequate (n = 860) or
excessive (n = 535). RESULTS: The predictors studied explained 25% of the
variance in birthweight. After adjustment for gestational age, WGP (both
categorical and continuous) was an important independent predictor of
birthweight. Infants of mothers with excessive weight gain had higher birthweight
(139 g; 95%CI 83, 196) than infants to mothers with adequate weight gain. In
contrast, birthweight was lower for infants of mothers with inadequate weight
gain (-148 g; 95%CI -202, -93). Measured as a continuous variable the infants
became 26 g heavier for each kilogram the mother gained in weight. In addition,
smoking, parity, sex and BMI also showed a positive association to birthweight.
Hypertension contributed only marginally and the impact of marital status and
maternal age did not reach statistical significance. CONCLUSION: As WGP is both
an important and modifiable risk factor for abnormal birthweight, and
recommendations exist for different BMI groups, it seems natural to put further
emphasis on advising pregnant women to stay within the recommended ranges.
PMID- 24351584
TI - The alarm and action levels of waist circumference in overweight and obese
Turkish women.
AB - SUMMARY: OBJECTIVE: To determine 'alarm and action levels' of waist
circumference (WC) in overweight and obese Turkish women and investigate the
relationship with cardiovascular risk factors.Research subjects and methods: Four
thousand three hundred and seventy-five women aged 18-81 years selected from
Istanbul Faculty of Medicine Obesity outpatient clinic. WC, waist-to-hip ratio
(WHR), body mass index [(BMI) (weight (kg)/height (m(2)))], blood pressure, and
biochemical parameters were analyzed. RESULTS: There was strong correlation
between BMI and WC levels (r: 0.852). The regression equation which describes
this correlation [WC = 1.68 * BMI (kg/m(2)) + 39.2 +/- 1.6] was applied to 500
random samples in order to define alarm and action levels for WC. Our results
indicated that alarm level of WC at BMI 25 kg/m(2) is 81 cm and action level of
WC at BMI 30 kg/m(2) is 90 cm. Validating samples were divided into three groups:
group I (WC levels below 81 cm, n: 421), group II (WC levels between 81 and 90
cm, n: 718), group III (WC levels above 90 cm, n: 2736) and further correlative
analyses were performed. Strong differences within alarm and action groups in
terms of cardiovascular risk factors were identified. The prevalence and mean
values of cardiovascular risk factors significantly increased with WC. In group 1
one or more risk factor prevalence was 64.8%, whereas in groups 2 and 3
prevalence was increased to 76.8 and 89%, respectively. CONCLUSION: Turkish women
with WC greater than 81 cm should gain no further weight and those greater than
90 cm should reduce their weight.
PMID- 24351585
TI - Analysis of the relationship between three coding polymorphisms in LEPR gene and
obesity in northern Chinese.
AB - SUMMARY: To determine the effect of variants in LEPR gene on obesity in northern
Chinese, three coding polymorphisms Arg109Lys (A/G), Asn656Lys (C/G) and
Pro1019Pro (C/T) were investigated for association with overweight and obesity.
By a case control design, 248 overweight or obese subjects and 351 lean normal
controls were recruited in Harbin region in north China. All three polymorphisms
were genotyped by Sequenom single nucleotide polymorphism (SNP) detection system
in both cases and controls. Genotypes for all three polymorphisms were in Hardy
Weinberg equilibrium in control subjects. Both groups had similar distribution of
alleles and genotypes created by the three coding polymorphisms of LEPR gene. No
differences in frequencies of genotypes or alleles between cases and controls for
any polymorphism individually were found by chi(2) analysis (p = 0.444, p = 0.507
and p = 0.662, respectively). Further, when the haplotypes of three polymorphisms
were assessed, no association for any haplotype of three polymorphisms was
revealed. In the present study, the three coding polymorphisms in LEPR gene were
firstly investigated in a population of northern Chinese. It was suggested that
the three coding polymorphisms in LEPR gene were unlikely to have major effects
on susceptibility to obesity in northern Chinese.:
PMID- 24351586
TI - Australian residence and heart disease risk in Vietnamese-born women.
AB - SUMMARY: The aim of this study was to compare the disease risk profile of
Vietnamese women who have lived in Australia for 2-15 years with a newly arrived
group of Vietnamese women. The design was a comparison of two cross-sectional
surveys (n = 256); one newly arrived (n = 159) and one (n = 97) who had lived in
Australia for 2-15 years. The main outcome measures were body mass index (BMI),
waist to hip ratio (WHR), total cholesterol (TC), high density lipoprotein
cholesterol (HDL-C) and TC/HDL ratio (atherogenic index). The longer-stay
residents had similar BMI (21.5 +/- 3.5 kg/m(2) vs. 21.1 +/- 3.1 kg/m(2), p =
0.2); lower waist (69.3 +/- 7.5 cm vs. 71.4 +/- 7.6 cm, p = 0.8), WHR (0.76 +/-
0.06 vs. 0.80 +/- 0.06, p = 0.0001), TC (4.7 +/- 1.0 mmol/L vs. 4.9 +/- 0.9
mmol/L, p = 0.001), TC/HDL (3.0 +/- 2.0 vs. 4.7 +/- 2.0, p = 0.006) and higher
hip measurement (91.1 +/- 7.4 cm vs. 89.1 +/- 5.6 cm, p = 0.009) than newly
arrived Vietnamese women. After adjustment for BMI and age the odds of having a
higher waist and WHR was significantly less for longer-stay residents, while the
odds of having larger hips was doubled. The odds of having a high atherogenic
index as estimated by the TC/HDL ratio was halved for the longer-stay residents
(p = 0.15). We conclude that Vietnamese women we surveyed who have lived in
Australia for 2-15 years have the same BMI, but lower levels of abdominal obesity
and lower atherogenic index than newly arrived Vietnamese women surveyed.:
PMID- 24351587
TI - Plasma fat concentration increases in visceral fat obese men during high
intensity endurance exercise.
AB - SUMMARY: The purpose of this study was to investigate differences in fat
metabolism between visceral fat obese (VF-Ob) and abdominal subcutaneous obese
(SF-Ob) men during "high-intensity endurance exercise". Fourteen obese (body mass
index >25 kg/m(2)) men were classified into two groups according to visceral fat
area using computed tomography; i.e., VF-Ob (n = 7; mean age, 52.0 +/- 2.5 year)
and SF-Ob (n = 7; mean age, 57.3 +/- 2.8 year) groups. Plasma fat concentration
and fat oxidation were measured at rest and during 60-min high-intensity (70% of
peak oxygen uptake) stationary cycling exercise. Plasma concentrations of free
fatty acid and glycerol were significantly higher (P <= 0.05) in VF-Ob men
compared with SF-Ob men during endurance exercise. However, no significant
difference was found in fat oxidation between VF-Ob and SF-Ob men (697 +/- 135
and 661 +/- 96 kJ/h, respectively) during high-intensity endurance exercise.
These results suggest that obesity phenotype affects plasma fat concentration
even during high-intensity exercise. It is likely that plasma fat concentrations
in visceral fat obese men during high-intensity endurance exercise are more
increased compared with during moderate-intensity endurance exercise. Despite the
difference in plasma fat concentration, total fat oxidation was similar in the
two obese phenotypes.:
PMID- 24351588
TI - A retrospective comparison of two very low energy diets on weight loss and health
status in obese women completing a 26-week program.
AB - SUMMARY: AIM: To retrospectively compare the effects of two very low energy
diets (VLED) on weight, girths, and health status by auditing clinic database.
METHODS: Obese women (n = 150) who consumed either 420 kcal/day (n = 75) or 800
kcal/day (n = 75) were retrospectively matched for age, height and entry weight.
The 26-week program comprised 12 weeks of 420 or 800 kcal/day energy intake then
12 weeks of reintroduction of normal food, with behavioural management. Pre-post
measures of weight, BMI, girths, blood pressure (BP) and blood glucose,
cholesterol and triglycerides were made. RESULTS: Within groups, all variables
significantly improved at 26 weeks, except fasting glucose (420 group only). In
the 420 and 800 groups, mean weight loss was 18.7 and 19.0 kg, BMI reduced by 7.7
and 7.0 kg/m(2), waist girth by 15.6 and 16.2 cm and hip girth by 16.5 and 14.1
cm (all p < 0.001). With weight loss expressed as % of entry weight, 58.7% of the
420 and 42.6% of the 800 groups lost >20% weight (p = 0.05). The only post
between group differences were in decreases in systolic BP (14 mmHg in 420 vs. 7
mmHg in 800; p < 0.05) and fasting glucose (0.1 mmol/L in 420 vs. 0.4 mmo1/L in
800; p < 0.05). CONCLUSIONS: Both levels of VLED with behavioural management
produced similar improvements in weight and health status in obese women after 26
weeks. A VLED of 800 kcal/day (instead of 420) might be recommended for calorie
control programs, to minimise health risks, while producing similar improvements
in weight and health.
PMID- 24351589
TI - The Trp64Arg of beta3-adrenoceptor gene and food intake in young healthy female.
PMID- 24351590
TI - [IgG subclasses targeting NC16A domain of BP180 in bullous pemphigoid].
AB - OBJECTIVE: To evaluate the distribution of four IgG subclasses targeting NC16A
domain of BP180 in bullous pemphigoid (BP) patients by developing and optimizing
a detection method of anti-BP180NC16A IgG subclasses so as to assess its
sensitivity and specificity. METHODS: Enzyme-linked immunosorbent assay (ELISA)
was developed with recombinant GST-BP180NC16A proteins generated by a bacterial
expression system. And 136 BP sera and 20 healthy control sera from our hospital
between 2009 and 2012 were tested by ELISA, and the cutoff value of four IgG
subclasses was set at an A reading corresponding to the mean value plus 3 times
of standard deviation of 20 healthy controls sera. Western blot was also used to
detect the IgG subclasses in patients with four positive IgG subclasses by ELISA.
RESULTS: The cutoff value of specific IgG1, IgG2, IgG3 and IgG4 were
0.113,0.196,0.154 and 0.120. The values of four IgG subclasses from 20 healthy
controls were lower than the corresponding cutoff value, making the detection
system good specificity. The positive rates of anti-BP180NC16A IgG1, IgG2, IgG3
and IgG4 antibody were 67.6% (92/136) , 45.6% (62/136), 50.7% (69/136) and 54.4%
(74/136) respectively in 136 BP sera. All four IgG subclasses were positive in 29
BP sera, accounting for 21.3%. The number of BP sera positive for at least one
IgG subclass were 112, accounting for 82.4%, indicating that the combined
sensitivity of four IgG subclasses was 82.4%. Western blot revealed that the
number of positivity was 15 and 14 for IgG1 and IgG4 respectively in 20 BP
patients with four IgG subclasses positive with ELISA. CONCLUSION: The
specificity of ELISA is excellent while its sensitivity needs further
improvements.
PMID- 24351591
TI - [Meta-analysis of risk factors for all-cause mortality of pulmonary
thromboembolism].
AB - OBJECTIVE: To evaluate the causes of death and risk factors of pulmonary
thromboembolism. METHODS: Pubmed, English Medical Current Contents, Chinese
Conference Data and Chinese Biomedical Database were searched from January 1995
up to May 2011. And the references of these studies were also examined.
Observational studies were assessed according to suggestion of quality assessment
with references. Randomized control trials (RCT) were assessed with Jadad scale.
Software RevMan 5.1 was used to examin the heterogeneity of trials. The fixed or
random effect model was employed to pool the risk ratio and 95%CI. The results
were expressed with risk ratio and 95%CI. RESULTS: Thirty-five studies with a
total number of 19 613 cases of pulmonary thromboembolism (PTE) were included for
final analysis. The average mortality rate was (10.7 +/- 7.6)% (range 0.5%
30.0%). And the following factors increased the total mortality of pulmonary
embolism: right ventricular hypokinesis or dysfunction (2.18(1.64-2.89), P =
0.000), elevated D-dimer (5.19(1.93-13.96), P = 0.001), elevated cardiac troponin
(cTnI) (4.01(2.77-5.81), P = 0.000), hypotension (2.76(1.25-6.09), P = 0.010),
malignancy (2.65(2.01-3.50), P = 0.000), congestive heart failure (1.90(1.62
2.22), P = 0.000), chronic lung disease (1.40(1.18-1.66), P = 0.000), tachycardia
(1.65(1.23-2.20), P = 0.000), immobility (1.74(1.36-2.21), P = 0.000) and age >
65 years (1.24 (1.13-1.37), P = 0.000), etc. When multiple factors co-existed,
the risk of death became more obvious. CONCLUSION: Elevated D-dimer, elevated
cTnI, hypotension, malignancy, right ventricular hypokinesis or dysfunction,
immobility, congestive heart failure, tachycardia, chronic lung disease, age > 65
years influence the mortality rate of pulmonary embolism.
PMID- 24351592
TI - [Epidemiology survey of gastrointestinal stromal tumor in Shanxi Province in
2011].
AB - OBJECTIVE: To explore the incidence and distribution of gastrointestinal stromal
tumor (GIST) in Shanxi Province. METHODS: Newly diagnosed and suspected GIST
cases of Shanxi Province on January 1, 2011 to December 31, 2011 were collected
from medical insurance records and hospital surveys. All specimens were sent to
the Department of Pathology at Shanxi Provincial Tumor Hospital for examinations.
And the data were analyzed by SPSS statistical analysis software. RESULTS: There
were 153 newly discovered cases of GIST in Shanxi Province in 2011. And its
distribution was scattered in different regions. The incidence was 4.3 per
million (153/35 932 786) . The high-risk areas were Taiyuan (n = 25) and Changzhi
(n = 25). There were 83 (54.2%) males and 70 (45.8%) females. And the incidence
of males was not different from that of females ( (4.5 vs 4.0 )per million, P >
0.05). The median onset age was 59 (24-79) years. A high incidence of GIST
occurred at an age range of 50-59 years (n = 33). Among the 139 patients, the
tumor locations were stomach (n = 88, 63.3%), small intestine (n = 21, 15.1%),
colon (n = 7, 5.0%), duodenum (n = 6, 4.3%), esophagus (n = 3, 2.2%) and extra
gastrointestinal (n = 14, 10.1%). And 113 cases had a record of tumor size. The
median diameter was 5.78 (0.3-25.0) cm. The largest diameter was <= 2 cm (n = 30,
26.5%), > 2-5 cm (n = 33, 29.2%), > 5-10 cm (n = 36, 31.9%) and >10 cm (n = 14,
12.4%). The cell types of 141 cases were spindle cell (n = 112, 79.4%),
epithelial (n = 11, 7.8%) and mixed (n = 18, 12.8%). CONCLUSIONS: Shanxi Province
has a low incidence of GIST. And no statistically significant difference exists
in the incidence between males and females. Taiyuan and Changzhi are relatively
more prevalent.
PMID- 24351593
TI - [Effects of on-pump beating-heart coronary artery bypass grafting for left-main
patients].
AB - OBJECTIVE: To explore the value of on-pump beating-heart coronary artery bypass
grafting (OnP-BH CABG) for left-main patients with coronary heart disease through
a comparative study with conventional coronary artery bypass grafting (CCABG).
METHODS: The clinical data were retrospectively analyzed for 66 patients of OnP
BH and 48 control cases undergoing CCABG from January 2009 to January 2012 at
Department of Cardiac Surgery, People's Hospital of Zhengzhou University.
RESULTS: OnP-BH group had a better clinical outcome than CCABG group. There were
obvious statistical difference in cardiopulmonary bypass (CPB) time, mean
ventilation time, intensive care unit stay and recovery time of plasma cardiac
troponin I (OnP-BH group vs CCABG group:(89 +/- 25) vs (117 +/- 28) min, (15 +/-
14) vs (27 +/- 19) h, (57 +/- 27) vs (79 +/- 34) h, (6.2 +/- 1.8) vs (7.0 +/-
2.4) d, all P < 0.05). The data of preoperative cTnI showed no significant
difference between two groups (P > 0.05) .However, after CPB, significant
intergroup difference existed in the level of cTnI (ug/L) OnP-BH group vs CCABG
group: (0.5 h after CPB: (0.132 +/- 0.022) vs (0.265 +/- 0.014) , 1 h after CPB:
(0.341 +/- 0.027) vs (0.572 +/- 0.046) , 1 h after operation: (0.641 +/- 0.036)
vs (0.932 +/- 0.047) , 6 h after operation: (1.212 +/- 0.765) vs (1.627 +/-
0.542) and 24 h after operation: (1.496 +/- 0.263) vs (1.734 +/- 0.328) , all P <
0.05). CONCLUSIONS: On-pump beating-heart coronary artery bypass grafting is a
feasible surgical approach for left-main patients. And it has a low risk and
causes less myocardial damage.
PMID- 24351594
TI - [Loss of expression and mechanism of early growth response gene-3 in human oral
squamous carcinoma].
AB - OBJECTIVE: To evaluate the expression of early growth response gene-3 (EGR3) in
human oral squamous carcinoma tissue, non-adjacent tissue and oral carcinoma cell
lines and detect the effects of EGR3 expression on the biological behaviors of
oral squamous carcinoma cell lines. METHODS: From October 2008 to December 2009,
the expression of EGR3 was detected in 20 human oral squamous carcinoma tissue,
non-tumor adjacent tissue and 2 oral carcinoma cell lines. The total-length
plasmid of EGR3 was constructed and transfected into oral squamous carcinoma line
Tca-8113 to observe the proliferation and apoptosis. RESULTS: There was a high
level expression of EGR3 mRNA in normal oral squamous epithelial and non-tumor
adjacent tissues (2.108 +/- 0.996 and 1.721 +/- 1.196). And a low-level
expression or a loss of EGR3 mRNA in human oral squamous carcinoma tissue and
oral carcinoma cell lines (0.007 +/- 0.005 and 0.007 +/- 0.001) (both P < 0.05).
Tca-8113 transfected by EGR3 plasmid had a high-level expression of EGR3 mRNA
capable of inhibiting the proliferation of Tca-8113 and promoting its apoptosis
dramatically. The stimulating index in overexpression of EGR3 was lower than
control group (0.35 +/- 0.11 vs 0.82 +/- 0.21, P < 0.05). After overexpression of
EGR3 in Tca-8113, the frequency of middle-Late stage of apoptosis (Annexin-V/PI
double positive) was higher than the frequency of vector group (23.12% +/- 6.65%
vs 5.96% +/- 0.98%, P < 0.05). CONCLUSION: A low-level expression or a loss of
EGR3 in human oral squamous carcinoma and an over-expression of EGR3 in human
oral squamous carcinoma may inhibit the proliferation and promote apoptosis of
oral squamous carcinoma.
PMID- 24351595
TI - [Clinical study of liver resection with bipolar radiofrequency device: Habib 4X].
AB - OBJECTIVE: To assess the application value of a new radiofrequency device Habib
4X in liver resection. METHODS: A retrospective study was performed during March
2010 to July 2011.Forty-four patients underwent liver resection with
radiofrequency device Habib 4X and another 54 patients traditional liver
resection.Intraoperative blood loss, blood transfusion, Pringle's maneuver
requirement, liver parenchyma transaction time, liver function recovery,
complications, mortality and recurrence were recorded. RESULTS: The mean
resection time was (67 +/- 22) min for Habib 4X group versus (93 +/- 23) min for
traditional group (P = 0.000). Pringle's maneuver was required in 10 patients
(22.7%) for Habib 4X group and 31 (57.4%) for traditional group (P = 0.001). The
mean blocking time was (7 +/- 2) vs (18 +/- 6) min (P = 0.001), mean blood loss
volume (243 +/- 132) vs (500 +/- 421) ml (P = 0.002). Postoperative recovery of
liver function was better in Habib 4X group than traditional group. None
developed mortality in Habib 4X group. And no resection margin recurred during a
18-month follow-up. CONCLUSIONS: Bipolar radiofrequency device Habib 4X is
recommended for pre-coagulation in hepatectomy. And the advantages of minimized
blood loss and reduced resection time result in its lower rates of morbidity and
mortality.
PMID- 24351596
TI - [Complication related factors and efficacy with flexible endoscopy of 101
esophageal foreign bodies].
AB - OBJECTIVE: To analyze the related factors of complications and treatment efficacy
with flexible endoscopy for esophageal foreign body (FB). METHODS: In a
retrospective study with consecutive data, 101 adults including 52 males and 49
females with esophageal FB impaction between January 2005 and December 2012
admitted into Department of Gastroenterology's Endoscopic Unit at Peking
University Third Hospital were included, aged (49 +/- 21) years. RESULTS: (1) FB
impaction in upper and middle esophagus accounted for 87.1% (n = 88) of all
esophageal FBs. No significant difference existed in interval time from impaction
to removal of FB impacted between upper, middle and lower esophagus (P > 0.05) .
(2) Patients with esophageal FB seeking hospital treatment accounted for 82.2% (n
= 83) within 24 h and 99.0% (n = 100) within 48 h. Food lump, fish bone, chicken
bone and fruit seeds accounted for 76.2% (n = 77). (3) Positive rates were 91.3%
(21/23) and 24.1% (7/29) with upper gastrointestinal barium contrast and chest or
abdominal plain film. The success rate was 94.1% (n = 95) with flexible endoscopy
for removal of FB. (4) Denture was the most difficult FB for removal. Four
patients in all 11 patients with denture impacted were not removed successfully
with flexible endoscopy. (5) The complication (except for mild scratch) rate was
48.5% (n = 49) and the perforation rate 3.0% (n = 3) . Whether complications took
place or not was independent of age, location of impaction, time from impaction
to removal and size of FB (all P > 0.05) , but dependent on piercing into
esophageal wall, concomitant with esophageal stricture and types of FB (all P <
0.01) . Whether perforation or not was independent of any above factor.
CONCLUSION: Esophageal FB should be removed as soon as possible within 24 h
especially for those with sharp edges and piercing into esophageal wall.
PMID- 24351597
TI - [Establishment of surgical blood ordering schedule and relative influential
factors for tumor patients].
AB - OBJECTIVE: To design a blood ordering schedule and explore the influencing
factors of blood utilizing and ordering for tumor surgical patients. METHODS: For
a total of 58 306 tumor surgical patients, 22 643 applications of blood ordering
and 7430 person-times of blood utilization from October 2002 to May 2012 were
retrospectively analyzed at Cancer Hospital of Chinese Academy of Medical
Sciences. Their clinical profiles and test results were analyzed. RESULTS: The
operative transfusion rate was 32.81%. According to the operation position and
the blood transfusion and preparation data, the surgical blood ordering schedule
of tumor patients was established. Patient gender, hemoglobin, hematocrit,
platelet, total protein and albumin level test results had significant effect on
the transfusion of red blood cells (OR = 0.797, 9.614, 1.949, 0.437,0.444, 2.038,
all P < 0.05). Patient gender, hemoglobin, hematocrit, activated partial
thromboplastin time, prothrombin time, albumin and total protein level test
results had significant effect on the transfusion of plasma (OR = 0.851, 1.367,
1.801, 1.652, 2.922, 2.224, 1.362, all P < 0.05) . CONCLUSION: For surgical tumor
patients, blood ordering should be based upon the test results of routine blood,
blood coagulation and protein level test results to ensure that blood transfusion
is both rational and safe.
PMID- 24351598
TI - [Bacteriological spectrum and drug susceptibility of pus from severe intra
abdominal infected patients with abdominal trauma].
AB - OBJECTIVE: To retrospectively analyze the bacteriological spectrum and drug
susceptibility of pus flora from abdominal traumatic patients with severe intra
abdominal infection. METHODS: A total of 41 severe intra-abdominal infected
patients with abdominal trauma were recruited to collect 123 abdominal pus
specimens. And the results of laboratory microbiology and drug sensitivity were
analyzed with the WHONET 5.4 software. RESULTS: A total of 297 strains of
bacteria were isolated at (7.2 +/- 2.3) strains for each patient. Gram-positive
bacteria accounted for 44.1% (131/297) , Gram-negative bacteria 55.2% (164/297)
and fungi 0.7% (2/297). The top five isolates were Escherichia coli,
Staphylococcus aureus, Klebsiella pneumonia, Enterococcus faecalis and
Pseudomonas aeruginosa. Those antibiotics highly sensitive (>90%) to Escherichia
coli included cefoperazone (91%), imipenem (98%); highly sensitive to Gram
positive cocci included teicoplanin (100%) and linezolid (100%). Staphylococcus
aureus was 100% sensitive to vancomycin. The agents with a high susceptibility to
Klebsiella pneumonia included imipenem (100%) and amikacin (79%). Ciprofloxacin
(90%) had the highest sensitivity to Pseudomonas aeruginosa. CONCLUSIONS: The
predominant bacteria of causing severe intra-abdominal infection of traumatic
patients is Gram-negative bacteria, but the infection of Gram-positive bacteria,
especially the ratio of Staphylococcus aureus infection is also comparatively
high. Cefoperazone, ciprofloxacin, imipenem, vancomycin, teicoplanin and
linezolid have higher antibacterial activity.
PMID- 24351599
TI - [Reliability of estrogen receptor, progesterone receptor and human epidermal
growth factor receptor 2 expression in breast cancer evaluated by
immunohistochemistry].
AB - OBJECTIVE: To evaluate the reliability of estrogen receptor (ER), progesterone
receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression in
breast cancer by immunohistochemistry and discuss their influencing factors.
METHODS: The pretreatment biopsy specimens were collected from 148 patients (from
Beijing Cancer Hospital between 2004 to 2010) with invasive breast cancer. After
reslicing and staining (ER:SP1, PR: 1E2, HER-2: 4B5), the status of ER, PR and
HER-2 was analyzed by a pathological expert with automated imaging system Ariol
MB-8. And their results were compared with the original reports. RESULTS: The
concordance rates between original reports and automated image system were
ER:76.35%, PR:49.32%, HER-2:63.51% while Kappa values 0.12 (P = 0.020) , 0.18 (P
= 0.002) and 0.08 (P = 0.200) respectively. And the concordance rates between
expert reports and automated image system were ER:93.92%, PR:81.08% and HER
2:76.35% while Kappa values 0.77 (P < 0.001) , 0.67 (P < 0.001) and 0.32 (P <
0.001) respectively. CONCLUSION: For the expressions of ER, PR and HER-2, the
disaccording results of original reports and automated image system may be mainly
due to the differences of antibodies, staining methods and interpretations.
PMID- 24351600
TI - [Effects of performing pelvic lymph node dissection before versus after radical
cystectomy].
AB - OBJECTIVE: To explore the efficacies of extended pelvic lymph node dissection (e
PLND) before or after radical cystectomy (RC). METHODS: From January 2003 to
January 2013, a total of 107 patients underwent e-PLND plus RC. And their
relevant clinical data were reviewed. Their median age was (62 +/- 10) years. The
e-PLND were divided into 10 regions and 6 groups according to the anatomic sites.
Forty-seven (43.9%) underwent RC after e-PLND (group A) and 60 (56.1%) had RC
before e-PLND (group B). Two groups were compared for operative duration, numbers
of lymph nodes removed, metastatic rates of lymph node, dissected lymph node
positive rates and operative complications. The results were analyzed with Chi
square or Student's test. RESULTS: Clinicopathological characteristics were
comparable for two groups (P > 0.05). The mean operative durations of e-PLND were
similar in both groups ( (83 +/- 27) vs (78 +/- 24) min , P > 0.05). The mean
operative durations of RC were significantly shorter in group A than those in
group B ( (79 +/- 41) vs (113 +/- 44) min, P < 0.01) . The mean number of lymph
nodes removed (25.5 +/- 9.7 vs 29.0 +/- 8.4) and the mean number of lymph nodes
removed at internal iliac (5.7 +/- 2.9 vs 7.2 +/- 3.5) and presacral (1.3 +/- 1.1
vs 2.5 +/- 1.6) regions were significantly fewer in group A than those in group B
(all P < 0.05). The metastatic rates of lymph node (34.0% (16/47) vs 31.7%
(19/60)), dissected lymph node positive rates (9.0% (108/1197) vs 7.5%
(130/1743)) and operative complications (23.4% (11/47) vs 20.0% (12/60)) were
similar in both groups (all P > 0.05). CONCLUSION: RC is performed preferably
after e-PLND, and internal iliac and presacral area should be dissected for
additional lymph nodes after RC.
PMID- 24351601
TI - [Comparative efficacies of non-surgical treatment for pediatric and adult
sagittal fractures of mandibular condyle].
AB - OBJECTIVE: To compare the efficacies of non-surgical treatment for pediatric and
adult sagittal fractures of mandibular condyle. METHODS: From January 1985 to
December 2010, our department treated 67 cases (82 sides) sagittal fractures of
mandibular condyle with occlusal splint at a height of 1-2 mm in molar region for
six months or other non-surgical treatment. Their clinical and radiological
remodeling of affected condyles after treatment were reviewed at six mouths, one
year and each year after treatment. They were divided into 2 groups according to
age. There were 28 patients (34 sides) aged over 12 years and 39 patients (48
sides) under 12 years. During a follow-up period of 2-25 years, mandibular
activity, mouth opening and parallel CT scan of condylar morphological
alterations were examined. RESULTS: Under 12-year-old group:good mandibular
function was observed in 39 patients. Maximal mouth opening over 35 mm was
achieved at 6 months.Only 11 of 39 patients had deviation on mouth opening at 6
months.Radiological studies showed that 32 condyles were complete remodeling and
16 condyles were partial remodeling. Poor remodeling was not observed. Over 12
year-old group:Ankylosis occurred in 4 joints. And 15 of 28 patients had
deviation on mouth opening at 6 months.Radiological studies showed the remodeling
of condyles was complete (n = 6), partial (n = 16) and poor (n = 12)
respectively. CONCLUSION: Mandibular functional recovery and condylar remodeling
are better in children with more powerful healing and reconstructing capacities.
PMID- 24351602
TI - [Sonographic features and diagnostic analysis of breast granulomatous diseases: a
report of 32 cases].
AB - OBJECTIVE: To evaluate the sonographic features of different pathological types
of breast granulomatous diseases and analyze the feasibility of ultrasonic
diagnosis. METHODS: A total of 32 patients with different pathological types of
breast granulomatous diseases were recruited. Their clinical and sonographic
findings were retrospectively reviewed. There were granulomatous mastitis (n =
12), breast xanthogranuloma (n = 5), lipogranuloma (n = 2), foreign body
granuloma (n = 1) and nonspecific granulation hyperplasia (n = 12). RESULTS:
Based on major sonographic appearances, they were divided into 4 patterns of
tubular, mass, diffuse and cystic mass. In 12 patients with granulomatous
mastitis and 12 patients with nonspecific granulation hyperplasia, the major
sonographic appearance was of tubular pattern (n = 6, 5), followed by mass
pattern (n = 4, 5) and diffuse pattern (n = 2, 2). Five patients with breast
xanthogranuloma and 1 patient with foreign body granuloma all showed mass
pattern. In 2 patients with lipogranuloma, one was of mass pattern and another
cystic pattern. In patients with granulomatous mastitis and patients with
nonspecific granulation hyperplasia, it showed a high diagnostic reliability of
ultrasound. The ratio of inflammatory lesion as the first sonographic diagnosis
was 10/12 and 8/12 respectively and ultrasonic BI-RADS 4b or above both only
1/12. However, the ratio of sonographic imaging in patients with xanthogranuloma
and Lipogranuloma mimic breast cancer, in which ultrasonic score as breast
imaging-reporting and data system (BI-RADS) 4b or above was 4/5 and 1/1
respectively. CONCLUSIONS: Ultrasound is valuable in evaluating the lesions in
patients with granulomatous mastitis and nonspecific granulation hyperplasia.
However a definite diagnosis is still dependent on histopathology.
PMID- 24351603
TI - [Significance of MACC1 protein expression in esophageal carcinoma].
AB - OBJECTIVE: To explore the expression of metastasis-associated colon cancer 1
(MACC1) proteins in esophageal carcinoma and neighboring tissues. METHODS: The
expressions of MACC1 were detected in 60 specimens of esophageal carcinoma and
neighboring tissues with immunohistochemistry and Western blotting. All the
specimens were selected from 2010-2012 of Guangfu Hospital of Jinhua, 38 males
and 22 females, aged (50 +/- 12) years. And the correlations of the expressions
of MACC1 proteins with the clinicopathologic features of esophageal carcinoma
were also analyzed. RESULTS: Expression of MACC1 protein was predominantly
located in cytoplasm and membrane. The positivity rates of MACC1 protein were
68.3% (41/60) in esophageal carcinoma tissue and there were significant
differences from those in neighboring tissue (25.0(15/60), P < 0.01). Western
blotting analysis showed that the expression level of MACC1 protein in esophageal
carcinoma was greater than that in corresponding adjacent tissues (0.64 +/- 0.05
vs 0.21 +/- 0.10, P < 0.05). Moreover, the positivity rates and relative
expressions of MACC1 showed significant correlations with TNM stage and pathology
grade (all P < 0.05). CONCLUSION: The abnormal expression of MACC1 may be
associated with malignant progression of esophageal carcinoma.
PMID- 24351604
TI - [Main mediated molecules of airway shear stress-stimulated MUC5AC extracellular
secretion].
AB - OBJECTIVE: To explore the main mediated molecules of mucin (MUC) 5AC
extracellular secretion stimulated by airway shear stress (SS). METHODS: The 16
human bronchial epithelial (HBE) cells were cultured and randomized divided by
Stata software into 5 groups: A. control group; B. SS stimulated group; C. SS
stimulated & NSC23766 (a specific inhibitor of Rac-1) incubated group; D. SS
stimulated & Cytochalasin D incubated group; E. Cortactin-siRNA (a small
interfering RNA of Cortactin) transfected & SS stimulated group. Each group
consisted of 6 parallel wells. Triplicate experiments were performed for
statistical analysis. Rhythmic rotating device was used to simulate the breathing
air flow mediated shear stress. The function of Cortactin was inhibited by
Cortactin-siRNA. The relative content of MUC5AC in supernatant was measured by
enzyme linked immunosorbent assay (ELISA). The p-Cortactin (phosphorylation
Cortactin) relative level, Cortactin relative level and the effect of
transfection were measured with Western blotting. And laser confocal microscope
was used to observe the polymerization of F-actin. RESULTS: The transfection of
Cortactin-siRNA successfully inhibited the function of Cortactin. The relative
content of MUC5AC was (0.210 +/- 0.013), (0.631 +/- 0.025), (0.473 +/- 0.112),
(0.330 +/- 0.067), (0.272 +/- 0.019) in groups A, B, C, D and E, the group B was
significantly higher than any other group (P = 0.000, 0.043, 0.000, 0.000). The
Cortactin relative level in group B (0.670 +/- 0.048) was significantly higher
than that in group E (0.132 +/- 0.014) (P < 0.01). But as compared with groups A,
C, D (0.641 +/- 0.016, 0.622 +/- 0.012, 0.653 +/- 0.027), there was no
significance (all P > 0.05). The p-Cortactin relative level in group B (0.582 +/-
0.067) was significantly higher than that in groups A, C, E (0.131 +/- 0.011,
0.393 +/- 0.045, 0.170 +/- 0.016) (P = 0.000, 0.021, 0.000). But as compared with
group D (0.511 +/- 0.029), there was no significance (P = 0.246). CONCLUSION: Rac
1, Cortactin and F-actin are the main mediated molecules of airway shear stress
stimulated MUC5AC extracellular secretion.
PMID- 24351605
TI - [Comparison of different methods for the isolation of human umbilical cord
mesenchymal stem cells].
AB - OBJECTIVE: To explore the most appropriate method for the isolation of human
umbilical cord mesenchymal stem cells (MSCs) through a comparison of different
methods. METHODS: Fifteen umbilical cord specimens from full-term healthy fetus
with caesarean birth were completely rinsed with phosphate buffer saline (PBS)
and sliced into 1 mm(3) tissue blocks after removal of umbilical vessels and
external membrane. These tissue blocks were averagely divided into 4 groups after
washing and centrifuge. Then four methods for the isolation of human umbilical
cord MSCs were compared: an explant culture and three enzymatic methods of
collagenaseII, collagenaseII/trypsin and collagenaseII/hyaluronidase. The count
of living cells was evaluated by trypan blue dye exclusion test. Cell morphology
was observed under inverted microscope. The expressions of cell surface markers
CD105, CD90, CD73, CD31, CD44, CD45, human leukocyte antigen-I (HLA-I) and human
leukocyte antigen class IImolecules (HLA-DR) were detected by immunofluorescent
staining. Cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5
diphenyltetrazolium bromide (MTT). RESULTS: The human umbilical cord MSCs were
successfully isolated by four isolated methods. However the isolation method used
profoundly altered the cell number and proliferation capacity of isolated cells.
Isolated cells using four methods were counted at (5.44 +/- 0.21)*10(5), (4.03 +/
0.24)*10(5), (4.91 +/- 0.33)*10(5) and (5.94 +/- 0.40)*10(5) respectively. More
cells were obtained with collagenaseII/hyaluronidase than other three methods
(all P < 0.05). Cells out of tissue blocks were observed at Day 9-11 and cells
were observed at Day 2 with three types of enzyme digestion. The fusion time of
cells were (18.5 +/- 3.5), (8.0 +/- 1.0), (7.5 +/- 1.5) and (3.5 +/- 0.5) days
respectively. The fusion time of cells obtained with collagenaseII/hyaluronidase
was lower than other methods (all P < 0.05). Cell morphology: polygonal,
irregular and of large volume for explant culture; relatively short and small for
collagenaseII and collagenaseII/trypsin methods; thin spindle for
collagenaseII/hyaluronidase method. Immunofluorescent staining revealed that
CD105, CD73, CD90 and CD44 were expressed in all groups while there was no
expression of CD31, CD45 or HLA-DR. And the cells obtained with
collagenaseII/hyaluronidase method were in a higher cell proliferation rate and
activity compared to other methods. CONCLUSION: The collagenaseII/hyaluronidase
method is optimal for the isolation of human umbilical cord MSCs than other
methods.
PMID- 24351606
TI - Paediatric exercise training in prevention and treatment.
AB - Exercise training is an underused intervention in paediatric healthcare. This is
surprising, since initial evidence demonstrates its effectiveness and safety;
furthermore it confers socioeconomic benefits for healthcare systems. Pilot
studies have assessed and confirmed the feasibility of exercise training in many
paediatric disease settings. However, more research is needed to understand the
pathophysiology, quantify treatment effects and monitor outcomes. A concerted
effort from researchers, health professionals and police makers will be necessary
to make exercise training an evidence-based and cost-effective intervention in
paediatric care.
PMID- 24351608
TI - Investigating the magnetic field-dependent conductivity in magnetite thin films
by modelling the magnetorefractive effect.
AB - A model of the magnetorefractive effect is developed for metallic oxides which
allows the MRE to be used to study the magnetic dependence of their transport and
phononic properties. This model is successfully applied to Fe3O4 and compared to
experiments on a series of magnetite thin films of varying thickness (10, 18, 37,
64 and 110 nm) deposited on MgO(111) substrates. Reflection spectra were modelled
as a function of film thickness, calculated from the Fresnel equations using an
Fe3O4 dielectric function consisting of Drude, hopping, phononic and d-s
transition conductivity processes. The reflectivity spectra of the different
thickness films are reasonably reproduced by the model and reveal that the Fe3O4
18.5 MUm phonon peak is shifted to a shorter wavelength in the thin films,
approaching the bulk value for t > 110 nm. The MRE spectra are modelled by
introducing a magnetic field dependence to the hopping and phononic terms, where
previous models have considered the magnetic dependence to be on the Drude term
only. In addition, the position of the Fe3O4 18.5 MUm phonon peak was also found
to shift in energy in the applied magnetic field by 0.05 MUm. These results
demonstrate the potential for using the MRE technique for probing the underlying
magnetoelectronic properties of thin film oxides in a quick and non-destructive
way.
PMID- 24351607
TI - Does prompt treatment of urinary tract infection in preschool children prevent
renal scarring: mixed retrospective and prospective audits.
AB - OBJECTIVE: To test whether active management of urinary tract infections (UTI) in
young children by general practitioners can reduce kidney scarring rates. DESIGN:
A comparison of two audits in Newcastle, of children aged <8 years, presenting
with UTIs ; a retrospective audit of conventional management during 1992-1995
(1990s) versus a prospective audit of direct access management during 2004-2011
(2000s). MAIN OUTCOME MEASURES: Kidney scarring rates, and their relationship
with time-to-treat. RESULTS: Children with a first UTI in the 2000s compared to
those in the 1990s, were referred younger, were half as likely to have a renal
scar (girls OR 0.47, 95% CI 0.29 to 0.76; boys 0.35, 0.16 to 0.81), and were
about 12 times more likely to have vesicoureteric reflux without scarring (girls
11.9, 4.3 to 33.5; boys 14.4, 4.3 to 47.6). In the 2000s, general practitioners
treated about half the children at first consultation. Children who were treated
within 3 days of their symptoms starting were one-third as likely to scar as
those whose symptoms lasted longer (0.33, 0.12 to 0.72). INTERPRETATION: Most
kidney defects seen in children after UTIs, are acquired scars, and in Newcastle,
active management in primary care has halved this rate.
PMID- 24351609
TI - Melody recognition in dichotic listening with or without frequency-place
mismatch.
AB - OBJECTIVES: The purpose of the study was to examine recognition of degraded
melodic stimuli in dichotic listening with or without frequency-place mismatch.
DESIGN: Melodic stimuli were noise vocoded with various number-of-channel
conditions in a dichotic and monaural processor. In the dichotic zipper
processor, the odd-indexed channels were tonotopically matched and presented to
the left ear while the even-indexed channels were tonotopically matched or upward
shifted in frequency and presented to the right ear. In the monaural processor,
all channels either unshifted or shifted were presented to the left ear alone.
Familiar melody recognition was measured in 16 normal-hearing adult listeners.
RESULTS: Performance for dichotically presented melodic stimuli did not differ
from that for monaurally presented stimuli even with low spectral resolution (8
channels). With spectral shift introduced in one ear, melody recognition
decreased with increasing spectral shift in a nonmonotonic fashion. With spectral
shift, melody recognition in dichotic listening was either not different or
superior in a few cases relative to the monaural condition. CONCLUSIONS: With no
spectral shift, cohesive fusion of dichotically presented melodic stimuli did not
seem to depend on spectral resolution. In spectrally shifted conditions,
listeners may have suppressed the partially shifted channels in the right ear and
selectively attended only to the unshifted ones, resulting in dichotic advantages
for melody recognition in some cases.
PMID- 24351610
TI - Do hearing loss and cognitive function modulate benefit from different binaural
noise-reduction settings?
AB - OBJECTIVES: Although previous research indicates that cognitive skills influence
benefit from different types of hearing aid algorithms, comparatively little is
known about the role of, and potential interaction with, hearing loss. This holds
true especially for noise reduction (NR) processing. The purpose of the present
study was thus to explore whether degree of hearing loss and cognitive function
modulate benefit from different binaural NR settings based on measures of speech
intelligibility, listening effort, and overall preference. DESIGN: Forty elderly
listeners with symmetrical sensorineural hearing losses in the mild to severe
range participated. They were stratified into four age-matched groups (with n =
10 per group) based on their pure-tone average hearing losses and their
performance on a visual measure of working memory (WM) capacity. The algorithm
under consideration was a binaural coherence-based NR scheme that suppressed
reverberant signal components as well as diffuse background noise at mid to high
frequencies. The strength of the applied processing was varied from inactive to
strong, and testing was carried out across a range of fixed signal-to-noise
ratios (SNRs). Potential benefit was assessed using a dual-task paradigm
combining speech recognition with a visual reaction time (VRT) task indexing
listening effort. Pairwise preference judgments were also collected. All
measurements were made using headphone simulations of a frontal speech target in
a busy cafeteria. Test-retest data were gathered for all outcome measures.
RESULTS: Analysis of the test-retest data showed all data sets to be reliable.
Analysis of the speech scores showed that, for all groups, speech recognition was
unaffected by moderate NR processing, whereas strong NR processing reduced
intelligibility by about 5%. Analysis of the VRT scores revealed a similar data
pattern. That is, while moderate NR did not affect VRT performance, strong NR
impaired the performance of all groups slightly. Analysis of the preference
scores collapsed across SNR showed that all groups preferred some over no NR
processing. Furthermore, the two groups with smaller WM capacity preferred strong
over moderate NR processing; for the two groups with larger WM capacity,
preference did not differ significantly between the moderate and strong settings.
CONCLUSIONS: The present study demonstrates that, for the algorithm and the
measures of speech recognition and listening effort used here, the effects of
different NR settings interact with neither degree of hearing loss nor WM
capacity. However, preferred NR strength was found to be associated with smaller
WM capacity, suggesting that hearing aid users with poorer cognitive function may
prefer greater noise attenuation even at the expense of poorer speech
intelligibility. Further research is required to enable a more detailed (SNR
dependent) analysis of this effect and to test its wider applicability.
PMID- 24351612
TI - Acclimatization to hearing aids.
AB - OBJECTIVE: Evidence for a clinically significant effect of acclimatization to
hearing aids is mixed. The aim of this study was to test for auditory
acclimatization effects in new unilateral and bilateral adult hearing aid users.
Hypotheses were i) there would be improvements in aided speech recognition in new
hearing aid users, compared with unaided listening and with a control group of
experienced hearing aid users, and ii) improvements would correlate with severity
of hearing loss, hearing aid use, and cognitive capacity. DESIGN: Speech
recognition in noise was measured for a 65 and a 75 dB SPL target with the Four
Alternative Auditory Feature test. Speech recognition in noise was measured
within 1 week of fitting and retested at 12 weeks postfitting in new hearing aid
users (16 unilateral and 16 bilateral fit). A control group of experienced
hearing aid users (n = 17) was tested over a similar time scale. Cognitive
capacity (reaction time and working memory) was measured, and self-reported
change in performance was assessed using the Speech, Spatial and Qualities of
Hearing Scale. Hearing aid use was assessed via data logging at the completion of
the study. RESULTS: Mean improvements in speech recognition of up to 4% were
observed across conditions and across groups consistent with a general practice
effect. On average there was no evidence of auditory acclimatization in the new
hearing aid user groups in terms of improvement in aided listening conditions
above that observed in unaided recognition or in the control group. There was no
correlation between change in aided speech recognition and severity of hearing
loss, hearing aid use, or cognitive capacity. New users reported significant
improvement over time in aided performance on a self-report questionnaire
compared with the control group. CONCLUSIONS: On average, there was no
improvement over time in new users' aided speech recognition relative to unaided
recognition or to the control group. This does not support a robust
acclimatization effect with nonlinear hearing aids. Test-retest variability may
obscure small average acclimatization effects; variability was not accounted for
by individual differences in severity of hearing loss, hearing aid use, or
cognitive capacity. New users' subjective report of increased benefit over time
may be reflective of other aspects of adjustment to hearing aid use not examined
in this study.
PMID- 24351611
TI - Competing speech perception in older and younger adults: behavioral and eye
movement evidence.
AB - OBJECTIVES: The purpose of this study was to examine eye-movement patterns in
older and younger adults to identify differences in how they respond to both to
be-attended and to-be-ignored speech. DESIGN: The study described in this article
used an eye-tracking paradigm to provide insight into the factors underlying
competing speech understanding in older (n = 23) and younger (n = 22) listeners.
Participants attended to a sentence presented in one ear and were instructed to
click on a visually displayed word that was heard in that ear while their eye
movements were monitored. A foil word also was shown on the screen. Either no
sound, steady state noise, or competing speech was presented to the other ear.
RESULTS: Comparisons between younger and older listeners on all three types of
indicators measured in this study (percent correct, response time, and eye
movement patterns) demonstrated that older adults were more greatly affected by
competing speech than were younger adults. Differences between the groups could
not be attributed to the presence of hearing loss in the older participants, as
performance for all subjects was at ceiling in quiet and none of the performance
metrics was significantly associated with degree of hearing loss. CONCLUSIONS:
Results of this study support the idea that age-related changes other than lack
of audibility or susceptibility to energetic masking negatively affect the
ability to understand speech in the presence of a competing message.
PMID- 24351613
TI - Sample size requirements for establishing clinical test-retest standards.
AB - OBJECTIVE: To define sample size requirements for establishing clinical serial
monitoring protocols. DESIGN: The 95% confidence bound of a critical difference
score is defined and used to identify false-negative regions suitable for sample
size calculation. RESULTS: Reference subject sample sizes vary from about 40 to
480 subjects, depending on the minimum acceptable error rates of the clinical
protocol. CONCLUSIONS: Sample size requirements for establishing test-retest
standards are generally defined and suitable for any serial monitoring protocol.
PMID- 24351614
TI - Absence seizures in children.
AB - INTRODUCTION: About 10% of seizures in children with epilepsy are typical absence
seizures. Absence seizures have a significant impact on quality of life. METHODS
AND OUTCOMES: We conducted a systematic review and aimed to answer the following
clinical question: What are the effects of treatments for typical absence
seizures in children? We searched: Medline, Embase, The Cochrane Library, and
other important databases up to July 2013 (Clinical Evidence reviews are updated
periodically; please check our website for the most up to date version of this
review). We included harms alerts from relevant organisations such as the US Food
and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK
Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 18
RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed
a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In
this systematic review we present information relating to the effectiveness and
safety of the following interventions: clonazepam, ethosuximide, gabapentin,
lamotrigine, and valproate.
PMID- 24351615
TI - Embryonic stem cells for lung fibrosis Is it the Prometheus myth or the Pandora's
Box?
PMID- 24351616
TI - Review of IPF diagnosis and management recommendations in Europe.
AB - Increased knowledge of Idiopathic Pulmonary Fibrosis (IPF) led to the development
of evidence-based diagnosis and treatment guidelines. A 2011 update of the
American Thoracic Society and the European Respiratory Society, together with the
Japanese Respiratory Society ( JRS) and Latin American Thoracic Association
(ALAT) provided new guidance on the diagnosis and treatment of IPF. Although the
2011 statement was a major advance, the application of guideline recommendations
has identified limitations.The guidelines focus primarily on 'definite' IPF, most
often diagnosed from typical High-Resolution Computed Tomography (HRCT)
appearances.The definition of 'probable' and 'possible' IPF is an advance, but
there is a lack of management guidance for these highly prevalent clinical
scenarios.The integration of HRCT and histological data in assigning of
diagnostic likelihood is also important, but does not always meet the needs of
some patients in whom a multidisciplinary diagnosis of definite IPF should be
made.Moreover, the committee did not find sufficient evidence to support the use
of any specific pharmacological therapy for patients with IPF.These issues
highlight the need for updating available clinical guidelines. Since 2012,
several national European recommendations documents and guidelines have been
updated.These generally follow the 2011 guidelines, but reflect more recently
available clinical study data. Following the publication of the CAPACITY trials
showing positive effects of pirfenidone in IPF and its approval in the European
Union,many of these updated guideline documents recommend that patients with mild
to-moderate IPF should be offered this therapy. This review analyses the recently
developed European country updates, comparing and contrasting recommendations on
the diagnosis and treatment of IPF.
PMID- 24351617
TI - Role of Propionibacterium Acnes in Sarcoidosis: A Meta-analysis.
AB - PURPOSE: To evaluate the available molecular evidence on the possible role of
Propionibacterium acnes (P. acnes) in the development of sarcoidosis, the meta
analysis was performed. METHODS: Case-control studies from January 1980 to
October 2012 on P. acnes associated with sarcoidosis were searched.Overall odds
ratios (OR) and 95% confidence intervals (CI) were obtained. RESULTS: Nine
studies were selected, which included 458 cases and 438 controls. 359 samples
from 458 patients were positive with a positive signal rate of 78.4% (33.3% to
92.3%). Significantly elevated sarcoidosis risk was associated with P. acnes (OR
= 19.58, 95% CI = 13.06 - 29.36). There was no evidence of publication bias.
CONCLUSIONS: The present data and meta-analysis supports an association between
P. acnes and some cases of sarcoidosis.
PMID- 24351618
TI - Granulomatous cutaneous sarcoidosis: diagnosis, relationship to systemic disease,
prognosis and treatment.
AB - Sarcoidosis is an antigen-mediated disease of unknown aetiology, characterized by
the presence of non-caseating epithelioid cell granulomas in multiple organs.
Cutaneous involvement in sarcoidosis is classified as specific, when biopsy
reveals non-caseating granulomas, and non-specific, typically erythema nodosum.
Granulomatous skin lesions occur in 9% to 37% of patients. The skin is the second
most commonly involved organ after the lung. A skin biopsy is easy to perform and
enables an early diagnosis with a minor invasive procedure. Some types of
specific lesions have prognostic significance and may help to predict the outcome
of the systemic disease. Maculopapules, subcutaneous nodules and scar sarcoidosis
are usually transient or tend to follow the course of the systemic disease. Skin
plaques and lupus pernio are associated with chronic sarcoidosis. Although most
cutaneous lesions of sarcoidosis do not cause significant morbidity and do not
require treatment, some have cosmetic importance because they may be disfiguring
and can have a strong psychosocial impact. Treatment of these lesions is a
challenge since they do not respond well to conventional treatments. This
manuscript reviews the clinical characteristics of the more frequent types of
specific cutaneous lesions of sarcoidosis, the relationship between cutaneous
involvement and systemic disease, the prognostic significance of lesions and the
present state of treatment of difficult cases of cutaneous sarcoidosis.
PMID- 24351619
TI - Anxiety, its relation to symptoms severity and anxiety sensitivity in
sarcoidosis.
AB - BACKGROUND: Sarcoidosis is a chronic systemic granulomatous disease of unknown
etiology. Previous studies demonstrated that patients with sarcoidosis had high
rates of depression and anxiety, and high magnitude of stressful life events. To
date, however, studies have not examined the anxiety sensitivity in sarcoid
patients and the relationship between psychopathology and symptom severity of
sarcoidosis.The aims of this study were to evaluate prevalence of depression and
anxiety in sarcoid patients, to assess their relationship with the disease
symptom severity, and to investigate the relationship between sarcoidosis and
anxiety sensitivity. METHODS: Thirty three sarcoid patients and thirty three
control subjects completed the following:Hospital Anxiety and Depression Scale,
Anxiety Sensitivity Index-3. RESULTS: The prevalence of depression (29%) and
anxiety (31%) was high among patients and comparable to results from other
research groups. Anxiety was significantly correlated with symptom severity and
was the main covariate of physical symptoms reported by sarcoid patients.
Patients exhibited an increase of their total anxiety sensitivity index and had
an increased number of physical concerns. CONCLUSIONS: These data confirmed
earlier reports that anxiety and depression are common in patients with
sarcoidosis and expanded on the previous results by showing that patients
exhibited increased anxiety sensitivity and a fear of physical sensations. These
results, together with the findings that anxiety was associated with sarcoidosis
symptom severity, suggest that targeting anxiety and the physical health concerns
may be important in the diagnosis and management of this disease.
PMID- 24351620
TI - Body composition profiling in a Dutch sarcoidosis population.
AB - Muscle atrophy is a common problem in many chronic inflammatory diseases. It may
occur as part of a generalized wasting process (cachexia) or be hidden due to
preservation of fatmass (sarcopenia, sarcopenic obesity). OBJECTIVES: The aim of
this study was to assess the prevalence of cachexia and muscle atrophy in
sarcoidosis and their association with disease activity and severity. METHODS: A
cross-sectional study was performed in 423 sarcoidosis patients. Fat-free mass
was assessed as an indirect measure of muscle mass by bioelectrical impedance
analysis. Patients were stratified based on body mass index (BMI) and fat-free
mass index (FFMI).Muscle atrophy was defined as FFMI <15 kg/m2 for women and <17
kg/m2 for men corresponding to <10th percentile of current reference values;
cachexia as BMI <20 combined with muscle atrophy.Multivariate linear regression
models were used to adjust for potential confounders. RESULTS: Of the patients
examined, 58% were categorized as overweight (37%) or obese (21%), whereas 7%
were underweight.Muscle atrophy was present in 25% and cachexia in 5%. Patients
with muscle atrophy showed significantly worse lung function (DLCO, FEV1, FVC,
all p-values <0.01) and impaired exercise capacity (VO2max, p<0.001). The
associations were most pronounced in patients with cachexia. Associations
remained significant after adjustment for potential confounders. CONCLUSIONS:
Muscle atrophy was present in 25% of sarcoidosis patients and was associated with
more severe pulmonary disease. Prospective studies with longitudinal design are
needed to assess the association between muscle atrophy and disease severity in
sarcoidosis.
PMID- 24351621
TI - Clinical profiles of 12 Chinese patients with diffuse panbronchiolitis.
AB - BACKGROUND: Diffuse panbronchiolitis (DPB) is an uncommon idiopathic inflammatory
disease, characterized by chronic sinusitis, respiratory bronchiolitis and
progressive airway obstruction. Without correct diagnosis and treatment, DPB may
progress to bronchiectasis, respiratory failure and even death. OBJECTIVE: To
help other clinicians deal with DPB. METHODS: Twelve Chinese patients (six
women;mean (SD) age 50(14.7) years) who were diagnosed as DPB were assessed
retrospectively for clinical, radiological, lung function, microbiological, and
other "characteristic" laboratory parameters. RESULTS: Most patients presented
with chronic cough, copious purulent sputum production, and exertional dyspnoea,
end-inspiratory crackles, and a history of sinusitis. Unlike DPB cases from
Japan, cold agglutination test in 11 out of 12 patients were negative, and the
CD4/CD8 lymphocyte ratio in all patients were normal or low. All patients had
moderate to severe small airway disfunction and hypoxemia. The mean values of
FEV1/FVC, and RV/TLC were 58.9%, and 41.5%, respectively. The most common HRCT
findings from this cohort of patients were bronchiectasis and bronchiolitis, with
nodular shadows distributed in a centrilobular pattern. Morphological examination
revealed peribronchiolar and bronchiolar wall inflammation composed of
lymphocytes, plasma cells, and histocytes. Few cases were not confirmed by
diagnostic criteria from Japan but clinically diagnosed as DPB due to satisfied
treatment response and typical clinical features. CONCLUSIONS: More DPB cases
need to be analyzed from Chinese population due to different presentations
compared to Japanese population. This experience should help other clinicians in
the investigation and management of DPB in non-Japanese patients.
PMID- 24351622
TI - Systemic glucocorticoid and anti-tuberculosis therapy in a patient with
coexisting tuberculosis and anthracosis.
AB - BACKGROUND: Tuberculous lymphadenitis is a common condition in underdeveloped and
developing countries. Anthracosis is the black pigmentation of bronchi caused by
the deposition of carbon, silica and quartz particles in the macrophages of the
bronchial mucosa and submucosa. There is a potential relationship between
bronchial anthracofibrosis and tuberculosis (TB). OBJECTIVES: A 66 year old woman
was referred to a chest diseases clinic when non-productive cough was noticed
during a preoperative examination. Computerized tomography (CT) of thorax showed
an infiltration in the right upper lobe and a lesion in the right apical lobe
adjacent to the trachea. Extensive diagnostic tests including mediastinoscopic
lymph node excision were performed. Anthracosis and coexisting tuberculosis were
diagnosed. RESULTS: Directly observed anti-TB therapy was immediately initiated.
Systemic prednisolone was initiated at a dose of 30 mg/day and tapered slowly to
the maintenance dose. Control thorax CT taken two months after the initiation of
therapy revealed that the right upper lobe bronchus was open and atelectasis of
the right upper lobe was resolved. Mediastinal calcified lymph nodes and fibrotic
changes of both apical regions were observed. Being in the 10th month of the
therapy, the patient is still totally asymptomatic in follow-ups. CONCLUSIONS:
Glucocorticoid therapy may raise some concerns in patients with TB. Here, we
present a case with anthracosis and coexistent TB, who responded very well to
simultaneous anti-TB and glucocorticoid therapy.
PMID- 24351623
TI - A case of disseminated nontuberculous mycobacteriosis and cerebellar
toxoplasmosis with autoantibody to interferon-gamma.
AB - Autoantibody against interferon-gamma has recently been associated with a variety
of opportunistic infections, particularly among Asians. We report the case of a
64-year-old Japanese woman who suffered from concomitant or sequential infections
of the skin, lungs, bronchi, uterus, and bladder with nontuberculous
mycobacteriosis, cerebellar toxoplasmosis, measles,herpes zoster, and vulvar
herpes. Blood mononuclear cells from the patient displayed intact cytokine
production in response to various stimuli and interferon-gamma. High-titer anti
interferon-gamma autoantibodies were detected in her serum. The atypical
pathology hampered early diagnosis, but indeterminate results of an interferon
gamma release assay could offer a simple clue suggesting the presence of
autoantibody.
PMID- 24351624
TI - Transthoracic lung ultrasonography in pulmonary alveolar proteinosis - case
report.
AB - A pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an
accumulation of surfactant components in lung alveoli. In diagnosis and
monitoring of the disease high resolution computed tomography (HRCT) is usually
used. Unfortunately, repeated exposure to CT scanning may be associated with an
increased risk of radiation. We present a patient in whom repeated transthoracic
lung ultrasonography (TLUS) brought parallel to HRCT data in assessing PAP
extent. It may indicate that TLUS might be potentially a relevant tool in
monitoring of PAP.
PMID- 24351625
TI - Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated
pulmonary sarcoidosis: a case report.
AB - Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can
affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare
form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with
each family showing a particular pattern of organ involvement, however while
Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph
node involvement is very rare. In this case report we describe the first reported
case of sarcoidosis in association with hereditary lysozyme amyloidosis.
PMID- 24351626
TI - Adaptation of soil physical measurement techniques for the delineation of mud and
lakebed sediments at Neusiedler See.
AB - For many water management issues of shallow lakes with non-consolidated sediments
hydrographic surveys of the open water area and reed belt areas are required. In
the frame of water management strategy for the steppe lake Neusiedler See,
located between Austria and Hungary, a hydrographic survey was conducted. In the
open water area (water depth >=1 m) a sediment echosounder was used. To validate
these measurements and to distinguish between water, mud, and sediment layers in
the shallow lake and reed belt area additional measurements were needed. As no
common standard methods are available yet, we developed a measurement system
based on two commonly applied soil physical measurement techniques providing
reproducible physical values: a capacitive sensor and a cone penetrometer
combined with GNSS-positioning enable dynamic measurements of georeferenced
vertical water-mud-bedsediments profiles. The system bases on site-specific
calibrated sensors and allows instantaneous, in situ measurements. The
measurements manifest a sharp water-mud interface by a sudden decline to smaller
water content which is a function of the dielectric permittivity. A second
decline indicates the transition to compacted mud. That is concurrently the
density where the penetrometer starts registering significant penetration
resistance. The penetrometer detects shallow lakebed-sediment layers. Within the
lake survey this measurement system was successfully tested.
PMID- 24351627
TI - Evaluation of piecewise polynomial equations for two types of thermocouples.
AB - Thermocouples are the most frequently used sensors for temperature measurement
because of their wide applicability, long-term stability and high reliability.
However, one of the major utilization problems is the linearization of the
transfer relation between temperature and output voltage of thermocouples. The
linear calibration equation and its modules could be improved by using regression
analysis to help solve this problem. In this study, two types of thermocouple and
five temperature ranges were selected to evaluate the fitting agreement of
different-order polynomial equations. Two quantitative criteria, the average of
the absolute error values |e|(ave) and the standard deviation of calibration
equation e(std), were used to evaluate the accuracy and precision of these
calibrations equations. The optimal order of polynomial equations differed with
the temperature range. The accuracy and precision of the calibration equation
could be improved significantly with an adequate higher degree polynomial
equation. The technique could be applied with hardware modules to serve as an
intelligent sensor for temperature measurement.
PMID- 24351628
TI - Combined hand gesture--speech model for human action recognition.
AB - This study proposes a dynamic hand gesture detection technology to effectively
detect dynamic hand gesture areas, and a hand gesture recognition technology to
improve the dynamic hand gesture recognition rate. Meanwhile, the corresponding
relationship between state sequences in hand gesture and speech models is
considered by integrating speech recognition technology with a multimodal model,
thus improving the accuracy of human behavior recognition. The experimental
results proved that the proposed method can effectively improve human behavior
recognition accuracy and the feasibility of system applications. Experimental
results verified that the multimodal gesture-speech model provided superior
accuracy when compared to the single modal versions.
PMID- 24351629
TI - Online least squares one-class support vector machines-based abnormal visual
event detection.
AB - The abnormal event detection problem is an important subject in real-time video
surveillance. In this paper, we propose a novel online one-class classification
algorithm, online least squares one-class support vector machine (online LS-OC
SVM), combined with its sparsified version (sparse online LS-OC-SVM). LS-OC-SVM
extracts a hyperplane as an optimal description of training objects in a
regularized least squares sense. The online LS-OC-SVM learns a training set with
a limited number of samples to provide a basic normal model, then updates the
model through remaining data. In the sparse online scheme, the model complexity
is controlled by the coherence criterion. The online LS-OC-SVM is adopted to
handle the abnormal event detection problem. Each frame of the video is
characterized by the covariance matrix descriptor encoding the moving
information, then is classified into a normal or an abnormal frame. Experiments
are conducted, on a two-dimensional synthetic distribution dataset and a
benchmark video surveillance dataset, to demonstrate the promising results of the
proposed online LS-OC-SVM method.
PMID- 24351630
TI - Design of a wireless sensor network platform for tele-homecare.
AB - The problem of an ageing population has become serious in the past few years as
the degeneration of various physiological functions has resulted in distinct
chronic diseases in the elderly. Most elderly are not willing to leave home for
healthcare centers, but caring for patients at home eats up caregiver resources,
and can overwhelm patients' families. Besides, a lot of chronic disease symptoms
cause the elderly to visit hospitals frequently. Repeated examinations not only
exhaust medical resources, but also waste patients' time and effort. To make
matters worse, this healthcare system does not actually appear to be effective as
expected. In response to these problems, a wireless remote home care system is
designed in this study, where ZigBee is used to set up a wireless network for the
users to take measurements anytime and anywhere. Using suitable measuring
devices, users' physiological signals are measured, and their daily conditions
are monitored by various sensors. Being transferred through ZigBee network, vital
signs are analyzed in computers which deliver distinct alerts to remind the users
and the family of possible emergencies. The system could be further combined with
electric appliances to remotely control the users' environmental conditions. The
environmental monitoring function can be activated to transmit in real time
dynamic images of the cared to medical personnel through the video function when
emergencies occur. Meanwhile, in consideration of privacy, the video camera would
be turned on only when it is necessary. The caregiver could adjust the angle of
camera to a proper position and observe the current situation of the cared when a
sensor on the cared or the environmental monitoring system detects exceptions.
All physiological data are stored in the database for family enquiries or
accurate diagnoses by medical personnel.
PMID- 24351631
TI - Structural-acoustic coupling effects on the non-vacuum packaging vibratory
cylinder gyroscope.
AB - The resonant shells of vibratory cylinder gyroscopes are commonly packaged in
metallic caps. In order to lower the production cost, a portion of vibratory
cylinder gyroscopes do not employ vacuum packaging. However, under non-vacuum
packaging conditions there can be internal acoustic noise leading to considerable
acoustic pressure which is exerted on the resonant shell. Based on the theory of
the structural-acoustic coupling, the dynamical behavior of the resonant shell
under acoustic pressure is presented in this paper. A finite element (FE) model
is introduced to quantitatively analyze the effect of the structural-acoustic
coupling. Several main factors, such as sealing cap sizes and degree of vacuum
which directly affect the vibration of the resonant shell, are studied. The
results indicate that the vibration amplitude and the operating frequency of the
resonant shell will be changed when the effect of structural-acoustic coupling is
taken into account. In addition, an experiment was set up to study the effect of
structural-acoustic coupling on the sensitivity of the gyroscope. A 32.4 mV/
degrees /s increase of the scale factor and a 6.2 Hz variation of the operating
frequency were observed when the radial gap size between the resonant shell and
the sealing cap was changed from 0.5 mm to 20 mm.
PMID- 24351632
TI - Sensor reliability evaluation scheme for target classification using belief
function theory.
AB - In the target classification based on belief function theory, sensor reliability
evaluation has two basic issues: reasonable dissimilarity measure among
evidences, and adaptive combination of static and dynamic discounting. One
solution to the two issues has been proposed here. Firstly, an improved
dissimilarity measure based on dualistic exponential function has been designed.
We assess the static reliability from a training set by the local decision of
each sensor and the dissimilarity measure among evidences. The dynamic
reliability factors are obtained from each test target using the dissimilarity
measure between the output information of each sensor and the consensus.
Secondly, an adaptive combination method of static and dynamic discounting has
been introduced. We adopt Parzen-window to estimate the matching degree of
current performance and static performance for the sensor. Through fuzzy theory,
the fusion system can realize self-learning and self-adapting with the sensor
performance changing. Experiments conducted on real databases demonstrate that
our proposed scheme performs better in target classification under different
target conditions compared with other methods.
PMID- 24351633
TI - New methodology of designing inexpensive hybrid control-acquisition systems for
mechatronic constructions.
AB - This article presents a new methodology for designing a hybrid control and
acquisition system consisting of a 32-bit SoC microsystem connected via a direct
Universal Serial Bus (USB) with a standard commercial off-the-shelf (COTS)
component running the Android operating system. It is proposed to utilize it
avoiding the use of an additional converter. An Android-based component was
chosen to explore the potential for a mobile, compact and energy efficient
solution with easy to build user interfaces and easy wireless integration with
other computer systems. This paper presents results of practical implementation
and analysis of experimental real-time performance. It covers closed control loop
time between the sensor/actuator module and the Android operating system as well
as the real-time sensor data stream within such a system. Some optimisations are
proposed and their influence on real-time performance was investigated. The
proposed methodology is intended for acquisition and control of mechatronic
systems, especially mobile robots. It can be used in a wide range of control
applications as well as embedded acquisition-recording devices, including energy
quality measurements, smart-grids and medicine. It is demonstrated that the
proposed methodology can be employed without developing specific device drivers.
The latency achieved was less than 0.5 ms and the sensor data stream throughput
was on the order of 750 KB/s (compared to 3 ms latency and 300 KB/s in
traditional solutions).
PMID- 24351634
TI - Active self-testing noise measurement sensors for large-scale environmental
sensor networks.
AB - Large-scale noise pollution sensor networks consist of hundreds of spatially
distributed microphones that measure environmental noise. These networks provide
historical and real-time environmental data to citizens and decision makers and
are therefore a key technology to steer environmental policy. However, the high
cost of certified environmental microphone sensors render large-scale
environmental networks prohibitively expensive. Several environmental network
projects have started using off-the-shelf low-cost microphone sensors to reduce
their costs, but these sensors have higher failure rates and produce lower
quality data. To offset this disadvantage, we developed a low-cost noise sensor
that actively checks its condition and indirectly the integrity of the data it
produces. The main design concept is to embed a 13 mm speaker in the noise sensor
casing and, by regularly scheduling a frequency sweep, estimate the evolution of
the microphone's frequency response over time. This paper presents our noise
sensor's hardware and software design together with the results of a test
deployment in a large-scale environmental network in Belgium. Our middle-range
value sensor (around ?50) effectively detected all experienced malfunctions, in
laboratory tests and outdoor deployments, with a few false positives. Future
improvements could further lower the cost of our sensor below ?10.
PMID- 24351635
TI - Ultra-low power high temperature and radiation hard complementary metal-oxide
semiconductor (CMOS) silicon-on-insulator (SOI) voltage reference.
AB - This paper presents an ultra-low power CMOS voltage reference circuit which is
robust under biomedical extreme conditions, such as high temperature and high
total ionized dose (TID) radiation. To achieve such performances, the voltage
reference is designed in a suitable 130 nm Silicon-on-Insulator (SOI) industrial
technology and is optimized to work in the subthreshold regime of the
transistors. The design simulations have been performed over the temperature
range of -40-200 degrees C and for different process corners. Robustness to
radiation was simulated using custom model parameters including TID effects, such
as mobilities and threshold voltages degradation. The proposed circuit has been
tested up to high total radiation dose, i.e., 1 Mrad (Si) performed at three
different temperatures (room temperature, 100 degrees C and 200 degrees C). The
maximum drift of the reference voltage V(REF) depends on the considered
temperature and on radiation dose; however, it remains lower than 10% of the mean
value of 1.5 V. The typical power dissipation at 2.5 V supply voltage is about 20
MUW at room temperature and only 75 MUW at a high temperature of 200 degrees C.
To understand the effects caused by the combination of high total ionizing dose
and temperature on such voltage reference, the threshold voltages of the used SOI
MOSFETs were extracted under different conditions. The evolution of V(REF) and
power consumption with temperature and radiation dose can then be explained in
terms of the different balance between fixed oxide charge and interface states
build-up. The total occupied area including pad-ring is less than 0.09 mm2.
PMID- 24351636
TI - Reliability of measured data for pH sensor arrays with fault diagnosis and data
fusion based on LabVIEW.
AB - Fault diagnosis (FD) and data fusion (DF) technologies implemented in the LabVIEW
program were used for a ruthenium dioxide pH sensor array. The purpose of the
fault diagnosis and data fusion technologies is to increase the reliability of
measured data. Data fusion is a very useful statistical method used for sensor
arrays in many fields. Fault diagnosis is used to avoid sensor faults and to
measure errors in the electrochemical measurement system, therefore, in this
study, we use fault diagnosis to remove any faulty sensors in advance, and then
proceed with data fusion in the sensor array. The average, self-adaptive and
coefficient of variance data fusion methods are used in this study. The pH
electrode is fabricated with ruthenium dioxide (RuO2) sensing membrane using a
sputtering system to deposit it onto a silicon substrate, and eight RuO2 pH
electrodes are fabricated to form a sensor array for this study.
PMID- 24351637
TI - Mobile sensing systems.
AB - Rich-sensor smart phones have made possible the recent birth of the mobile
sensing research area as part of ubiquitous sensing which integrates other areas
such as wireless sensor networks and web sensing. There are several types of
mobile sensing: individual, participatory, opportunistic, crowd, social, etc. The
object of sensing can be people-centered or environment-centered. The sensing
domain can be home, urban, vehicular... Currently there are barriers that limit
the social acceptance of mobile sensing systems. Examples of social barriers are
privacy concerns, restrictive laws in some countries and the absence of economic
incentives that might encourage people to participate in a sensing campaign.
Several technical barriers are phone energy savings and the variety of sensors
and software for their management. Some existing surveys partially tackle the
topic of mobile sensing systems. Published papers theoretically or partially
solve the above barriers. We complete the above surveys with new works, review
the barriers of mobile sensing systems and propose some ideas for efficiently
implementing sensing, fusion, learning, security, privacy and energy saving for
any type of mobile sensing system, and propose several realistic research
challenges. The main objective is to reduce the learning curve in mobile sensing
systems where the complexity is very high.
PMID- 24351638
TI - Experimental implementation of a biometric laser synaptic sensor.
AB - We fabricate a biometric laser fiber synaptic sensor to transmit information from
one neuron cell to the other by an optical way. The optical synapse is
constructed on the base of an erbium-doped fiber laser, whose pumped diode
current is driven by a pre-synaptic FitzHugh-Nagumo electronic neuron, and the
laser output controls a post-synaptic FitzHugh-Nagumo electronic neuron. The
implemented laser synapse displays very rich dynamics, including fixed points,
periodic orbits with different frequency-locking ratios and chaos. These regimes
can be beneficial for efficient biorobotics, where behavioral flexibility
subserved by synaptic connectivity is a challenge.
PMID- 24351639
TI - Applications of delayed fluorescence from photosystem II.
AB - While photosystem II (PSII) of plants utilizes light for photosynthesis, part of
the absorbed energy may be reverted back and dissipated as long-term fluorescence
(delayed fluorescence or DF). Because the generation of DF is coupled with the
processes of forward photosynthetic activities, DF contains the information about
plant physiological states and plant-environment interactions. This makes DF a
potentially powerful biosensing mechanism to measure plant photosynthetic
activities and environmental conditions. While DF has attracted the interest of
many researchers, some aspects of it are still unknown because of the complexity
of photosynthetic system. In order to provide a holistic picture about the
usefulness of DF, it is meaningful to summarize the research on DF applications.
In this short review, available literature on applications of DF from PSII is
summarized.
PMID- 24351640
TI - A practical monitoring system for the structural safety of mega-trusses using
wireless vibrating wire strain gauges.
AB - Sensor technologies have been actively employed in structural health monitoring
(SHM) to evaluate structural safety. To provide stable and real-time monitoring,
a practical wireless sensor network system (WSNS) based on vibrating wire strain
gauges (VWSGs) is proposed and applied to a building under construction. In this
WSNS, the data measured from each VWSG are transmitted to the sensor node via a
signal line and then transmitted to the master node through a short-range
wireless communication module (operating on the Industrial, Scientific, and
Medical (ISM) band). The master node also employs a long-range wireless
communication module (Code Division Multiple Access-CDMA) to transmit the
received data from the sensor node to a server located in a remote area, which
enables a manager to examine the measured data in real time without any time or
location restrictions. In this study, a total of 48 VWSGs, 14 sensor nodes, and
seven master nodes were implemented to measure long-term strain variations of
mega-trusses in an irregular large-scale building under construction. Based on
strain data collected over a 16-month period, a quantitative evaluation of the
construction process was performed to determine the aspects that exhibit the
greatest influence on member behavior and to conduct a comparison with numerical
simulation results. The effect of temperature stress on the structural elements
was also analyzed. From these observations, the feasibility of a long-term WSNS
based on VWSGs to evaluate the structural safety of an irregular building under
construction was confirmed.
PMID- 24351641
TI - Study on the application of an ultra-high-frequency fractal antenna to partial
discharge detection in switchgears.
AB - The ultra-high-frequency (UHF) method is used to analyze the insulation condition
of electric equipment by detecting the UHF electromagnetic (EM) waves excited by
partial discharge (PD). As part of the UHF detection system, the UHF sensor
determines the detection system performance in signal extraction and recognition.
In this paper, a UHF antenna sensor with the fractal structure for PD detection
in switchgears was designed by means of modeling, simulation and optimization.
This sensor, with a flat-plate structure, had two resonance frequencies of 583
MHz and 732 MHz. In the laboratory, four kinds of insulation defect models were
positioned in the testing switchgear for typical PD tests. The results show that
the sensor could reproduce the electromagnetic waves well. Furthermore, to
optimize the installation position of the inner sensor for achieving best
detection performance, the precise simulation model of switchgear was developed
to study the propagation characteristics of UHF signals in switchgear by finite
difference time-domain (FDTD) method. According to the results of simulation and
verification test, the sensor should be positioned at the right side of bottom
plate in the front cabinet. This research established the foundation for the
further study on the application of UHF technique in switchgear PD online
detection.
PMID- 24351642
TI - Mobile monitoring and embedded control system for factory environment.
AB - This paper proposes a real-time method to carry out the monitoring of factory
zone temperatures, humidity and air quality using smart phones. At the same time,
the system detects possible flames, and analyzes and monitors electrical load.
The monitoring also includes detecting the vibrations of operating machinery in
the factory area. The research proposes using ZigBee and Wi-Fi protocol
intelligent monitoring system integration within the entire plant framework. The
sensors on the factory site deliver messages and real-time sensing data to an
integrated embedded systems via the ZigBee protocol. The integrated embedded
system is built by the open-source 32-bit ARM (Advanced RISC Machine) core
Arduino Due module, where the network control codes are built in for the ARM
chipset integrated controller. The intelligent integrated controller is able to
instantly provide numerical analysis results according to the received data from
the ZigBee sensors. The Android APP and web-based platform are used to show
measurement results. The built-up system will transfer these results to a
specified cloud device using the TCP/IP protocol. Finally, the Fast Fourier
Transform (FFT) approach is used to analyze the power loads in the factory zones.
Moreover, Near Field Communication (NFC) technology is used to carry out the
actual electricity load experiments using smart phones.
PMID- 24351643
TI - Events as power source: wireless sustainable corrosion monitoring.
AB - This study presents and implements a corrosion-monitoring wireless sensor
platform, EPS (Events as Power Source), which monitors the corrosion events in
reinforced concrete (RC) structures, while being powered by the micro-energy
released from the corrosion process. In EPS, the proposed corrosion-sensing
device serves both as the signal source for identifying corrosion and as the
power source for driving the sensor mote, because the corrosion process (event)
releases electric energy; this is a novel idea proposed by this study. For
accumulating the micro-corrosion energy, we integrate EPS with a COTS (Commercial
Off-The-Shelf) energy-harvesting chip that recharges a supercapacitor. In
particular, this study designs automatic energy management and adaptive
transmitted power control polices to efficiently use the constrained accumulated
energy. Finally, a set of preliminary experiments based on concrete pore solution
are conducted to evaluate the feasibility and the efficacy of EPS.
PMID- 24351644
TI - Application of remote power-by-light switching in a simplified BOTDA sensor
network.
AB - We propose and demonstrate the use of spatial multiplexing as a means to reduce
the costs of distributed sensing networks. We propose a new scheme in which
remote power-by-light switching is deployed to scan multiple branches of a
distributed sensing network based on Brillouin Optical Time Domain Analysis
(BOTDA) sensors. A proof-of-concept system is assembled with two 5-km sensor
fiber branches that are alternatively monitored using a fast remotely controlled
and optically powered optical switch. The multiplexed distributed sensor fibers
were located 10 km away from the interrogation unit and a Raman pump is used to
remotely power the switch. Furthermore, the deployed BOTDA unit uses an
alternative configuration that can lead to simplified setups.
PMID- 24351645
TI - MusA: using indoor positioning and navigation to enhance cultural experiences in
a museum.
AB - In recent years there has been a growing interest in the use of multimedia mobile
guides in museum environments. Mobile devices have the capabilities to detect the
user context and to provide pieces of information suitable to help visitors
discover and follow the logical and emotional connections that develop during the
visit. In this scenario, location based services (LBS) currently represent an
asset, and the choice of the technology to determine users' position, combined
with the definition of methods that can effectively convey information, become
key issues in the design process. In this work, we present Museum Assistant
(MusA), a general framework for the development of multimedia interactive guides
for mobile devices. Its main feature is a vision-based indoor positioning system
that allows the provision of several LBS, from way-finding to the contextualized
communication of cultural contents, aimed at providing a meaningful exploration
of exhibits according to visitors' personal interest and curiosity. Starting from
the thorough description of the system architecture, the article presents the
implementation of two mobile guides, developed to respectively address adults and
children, and discusses the evaluation of the user experience and the visitors'
appreciation of these applications.
PMID- 24351646
TI - Data mining for wearable sensors in health monitoring systems: a review of recent
trends and challenges.
AB - The past few years have witnessed an increase in the development of wearable
sensors for health monitoring systems. This increase has been due to several
factors such as development in sensor technology as well as directed efforts on
political and stakeholder levels to promote projects which address the need for
providing new methods for care given increasing challenges with an aging
population. An important aspect of study in such system is how the data is
treated and processed. This paper provides a recent review of the latest methods
and algorithms used to analyze data from wearable sensors used for physiological
monitoring of vital signs in healthcare services. In particular, the paper
outlines the more common data mining tasks that have been applied such as anomaly
detection, prediction and decision making when considering in particular
continuous time series measurements. Moreover, the paper further details the
suitability of particular data mining and machine learning methods used to
process the physiological data and provides an overview of the properties of the
data sets used in experimental validation. Finally, based on this literature
review, a number of key challenges have been outlined for data mining methods in
health monitoring systems.
PMID- 24351647
TI - Floor covering and surface identification for assistive mobile robotic real-time
room localization application.
AB - Assistive robotic applications require systems capable of interaction in the
human world, a workspace which is highly dynamic and not always predictable.
Mobile assistive devices face the additional and complex problem of when and if
intervention should occur; therefore before any trajectory assistance is given,
the robotic device must know where it is in real-time, without unnecessary
disruption or delay to the user requirements. In this paper, we demonstrate a
novel robust method for determining room identification from floor features in a
real-time computational frame for autonomous and assistive robotics in the human
environment. We utilize two inexpensive sensors: an optical mouse sensor for
straightforward and rapid, texture or pattern sampling, and a four color
photodiode light sensor for fast color determination. We show how data relating
floor texture and color obtained from typical dynamic human environments, using
these two sensors, compares favorably with data obtained from a standard webcam.
We show that suitable data can be extracted from these two sensors at a rate 16
times faster than a standard webcam, and that these data are in a form which can
be rapidly processed using readily available classification techniques, suitable
for real-time system application. We achieved a 95% correct classification
accuracy identifying 133 rooms' flooring from 35 classes, suitable for fast
coarse global room localization application, boundary crossing detection, and
additionally some degree of surface type identification.
PMID- 24351648
TI - Fractional modeling of the AC large-signal frequency response in magnetoresistive
current sensors.
AB - Fractional calculus is considered when derivatives and integrals of non-integer
order are applied over a specific function. In the electrical and electronic
domain, the transfer function dependence of a fractional filter not only by the
filter order n, but additionally, of the fractional order alpha is an example of
a great number of systems where its input-output behavior could be more exactly
modeled by a fractional behavior. Following this aim, the present work shows the
experimental ac large-signal frequency response of a family of electrical current
sensors based in different spintronic conduction mechanisms. Using an ac
characterization set-up the sensor transimpedance function Z(t)(JF) is obtained
considering it as the relationship between sensor output voltage and input
sensing current, Z(t)(jf)= V(o, sensor)(jf)/I(sensor)(jf). The study has been
extended to various magnetoresistance sensors based in different technologies
like anisotropic magnetoresistance (AMR), giant magnetoresistance (GMR), spin
valve (GMR-SV) and tunnel magnetoresistance (TMR). The resulting modeling shows
two predominant behaviors, the low-pass and the inverse low-pass with fractional
index different from the classical integer response. The TMR technology with
internal magnetization offers the best dynamic and sensitivity properties opening
the way to develop actual industrial applications.
PMID- 24351649
TI - LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in
neurons: implications for Parkinson disease.
AB - Mitophagy, or the selective clearance of mitochondria by autophagy, plays a key
role in mitochondrial quality control. Due to their postmitotic nature and
metabolic dependence on mitochondria, either insufficient or unchecked mitophagy
is detrimental to neurons. To better understand signals that regulate this
process, we treated primary rat cortical neurons with the electron transport
chain complex I inhibitor rotenone to elicit mitophagy. The lipidomic profiles of
mitochondria from control or injured neurons were analyzed by mass spectrometry,
revealing a significant redistribution of cardiolipin (CL) from the inner
mitochondrial membrane to the outer mitochondrial surface. Direct liposome
binding studies, computational modeling, and site-directed mutagenesis indicate
that microtubule-associated protein 1 light chain 3 (MAP1LC3/LC3), a defining
protein of autophagic membranes, binds to CL. Preventing this interaction
inhibits rotenone-induced mitochondrial delivery to autophagosomes and lysosomes
and attenuates mitochondrial loss as assessed by western blot. The CL-LC3
interaction is also important for mitophagy induced by other stimuli including 6
hydroxydopamine, another chemical model of Parkinson disease. Given that a
conserved LC3 phosphorylation site is adjacent to key residues involved in CL
binding, signaling pathways could potentially modulate this interaction to fine
tune the mitochondrial recycling response.
PMID- 24351650
TI - The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy.
AB - T lymphocytes, the master regulators of immunity, have an unusual lifestyle.
Equipped with a clonally distributed receptor they remain resting for long
periods of time but go into overdrive when encountering antigen. Antigen
recognition triggers an activation program that results in massive proliferation,
differentiation into effector/memory cells, egress from lymphoid storage sites,
and production of an array of cytokines. To adapt to the sudden demand for energy
and biosynthetic macromolecules, T cells resort to aerobic glycolysis, relying on
the Warburg effect to provide sufficient ATP and precursor molecules. Metabolic
adaptation to the biosynthetic needs includes upregulation of autophagy, a
catabolic process resulting in the degradation of cytoplasmic contents. The close
connection between a metabolic switch, proliferative expansion, and functional
differentiation connects the metabolic conditions in the cell to normal and
pathogenic immunity.
PMID- 24351652
TI - Serum 1,25-dihydroxyvitamin d and the development of kidney dysfunction in a
Japanese community.
AB - BACKGROUND: Recent evidence indicates that vitamin D deficiency is associated
with an increased risk of renal impairment, but studies addressing the influence
of vitamin D deficiency on the development of chronic kidney disease (CKD) in the
general Asian population have been few. METHODS AND RESULTS: A total of 2,417
community-dwelling individuals without CKD stage 3-5 aged >=40 years were
followed for 5 years (mean age, 60 years; women, 59.1%). The cumulative incidence
of CKD stage 3-5, defined as estimated glomerular filtration rate (eGFR)
<60ml.min(-1).1.73m(-2), and the rate of decline in eGFR according to quartile of
serum 1,25-dihydroxyvitamin D (1,25(OH)2D), were estimated. During follow-up, 378
subjects experienced CKD stage 3-5. The age- and sex-adjusted incidence of CKD
stage 3-5 increased significantly with decreasing serum 1,25(OH)2D (P for trend
<0.001). Compared with the highest quartile, the multivariate-adjusted odds ratio
for the development of CKD stage 3-5 was 1.90 in the lowest quartile and 1.74 in
the second lowest quartile, after adjusting for confounding factors.
Additionally, lower serum 1,25(OH)2D was significantly associated with a greater
change in eGFR (-0.10ml.min(-1).1.73m(-2).year(-1) per 10-pg/ml decrement in
serum 1,25(OH)2D). CONCLUSIONS: Lower serum 1,25(OH)2D is a significant risk
factor for the development of CKD stage 3-5 in the general Asian population.
PMID- 24351651
TI - ATM-dependent chromatin remodeler Rsf-1 facilitates DNA damage checkpoints and
homologous recombination repair.
AB - As a member of imitation switch (ISWI) family in ATP-dependent chromatin
remodeling factors, RSF complex consists of SNF2h ATPase and Rsf-1. Although it
has been reported that SNF2h ATPase is recruited to DNA damage sites (DSBs) in a
poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent manner in DNA damage response
(DDR), the function of Rsf-1 is still elusive. Here we show that Rsf-1 is
recruited to DSBs confirmed by various cellular analyses. Moreover, the initial
recruitment of Rsf-1 and SNF2h to DSBs shows faster kinetics than that of
gammaH2AX after micro-irradiation. Signals of Rsf-1 and SNF2h are retained over
30 min after micro-irradiation, whereas gammaH2AX signals are gradually reduced
at 10 min. In addition, Rsf-1 is accumulated at DSBs in ATM-dependent manner, and
the putative pSQ motifs of Rsf-1 by ATM are required for its accumulation at
DSBs. Furtheremore, depletion of Rsf-1 attenuates the activation of DNA damage
checkpoint signals and cell survival upon DNA damage. Finally, we demonstrate
that Rsf-1 promotes homologous recombination repair (HRR) by recruiting resection
factors RPA32 and Rad51. Thus, these findings reveal a new function of chromatin
remodeler Rsf-1 as a guard in DNA damage checkpoints and homologous recombination
repair.
PMID- 24351653
TI - A well-oiled machine: DNM2/dynamin 2 helps keep hepatocyte lipophagy running
smoothly.
AB - Liver steatosis is characterized by an abnormal buildup of hepatic fat content.
Our understanding of how this fat balance is normally regulated remains limited.
Recently, autophagy has been implicated as one potential mechanism contributing
to the breakdown of cytoplasmic fat storage organelles known as lipid droplets
(LDs) in the hepatocyte. In our recent publication, we show that the large GTPase
DNM2/dynamin 2 helps promote lipophagic turnover by facilitating the scission of
nascent lysosomes from autolysosomal tubules during autophagic flux. Genetic and
pharmacological perturbations of DNM2 function in cultured cells result in the
generation of aberrantly long autolysosomal reformation tubules. As a
consequence, hepatocytes accumulate LDs. An alleviation of DNM2 inhibition
results in the scission of reformation tubules and the return of LD turnover to
normal levels. DNM2 therefore plays a critical role in the regulation of the
lipophagic machinery in the hepatocyte.
PMID- 24351654
TI - RevSex duplication-induced and sex-related differences in the SOX9 regulatory
region chromatin landscape in human fibroblasts.
AB - It was recently shown that duplications of the RevSex element, located 0.5 Mb
upstream of SOX9, cause XX-disorder of sex development (DSD), and that deletions
cause XY-DSD. To explore how a 148 kb RevSex duplication could have turned on
gonadal SOX9 expression in the absence of SRY in an XX-male, we examined the
chromatin landscape in primary skin fibroblast cultures from the index, his
RevSex duplication-carrier father and six controls. The ENCODE project supports
the notion that chromatin state maps show overlap between different cell types,
i.e., that our study of fibroblasts could be of biological relevance. We examined
the SOX9 regulatory region by high-resolution ChIP-on-chip experiments (a kind of
"chromatin-CGH") and DNA methylation investigations. The RevSex duplication was
associated with chromatin changes predicting better accessibility of the SRY
responsive TESCO enhancer region 14-15 kb upstream of SOX9. Four kb downstream of
the TESCO evolutionary conserved region, a peak of the enhancer/promoter
associated H3K4me3 mark was found together with a major dip of the repressive
H3K9me3 chromatin mark. Similar differences were also found when three control
males were compared with three control females. A marked male/female difference
was a more open chromatin signature in males starting ~400 kb upstream of SOX9
and increasing toward the SOX9 promoter. In the RevSex duplication-carrier
father, two positions of DNA hypomethylation were also found, one corresponding
to the H3K4me3 peak mentioned above. Our results suggest that the RevSex
duplication could operate by inducing long-range epigenetic changes. Furthermore,
the differences in chromatin state maps between males and females suggest that
the Y chromosome or X chromosome dosage may affect chromatin conformation, i.e.,
that sex-dependent gene regulation may take place by chromatin modification.
PMID- 24351655
TI - Similarity in joint and mucous bleeding syndromes in type 2N von Willebrand
disease and severe hemophilia A coexisting with type 1 von Willebrand disease in
two Chinese pedigrees.
AB - In this study, we investigated the molecular basis of two unrelated Chinese
patients with hemostatic disorders. The proband of the first family had severe
hemophilia A (HA) coexisting with type 1 von Willebrand disease (VWD) and the
proband of the second family had type 2N VWD. Both probands had similar
phenotypes, which included joint and mucosal bleeding, very low factor VIII
(FVIII) activity (FVIII:C), and moderate reductions in VWF antigen (VWF:Ag) and
VWF ristocetin cofactor activity (VWF:Rco), as well as a normal multimeric
pattern. One FVIII mutation and three VWF mutations were identified: FVIII
p.R446* and VWF heterozygous p.E216K mutations were detected in proband 1 and
compound heterozygosity of VWF mutations (p.R816W and c.1911delC) in proband 2.
Transient expression studies in HEK293T cells proved that R816W mutation
abolished the binding of FVIII to VWF and slightly impaired protein synthesis and
secretion; 1911delC mutation mainly impaired VWF protein synthesis and secretion.
These results provided insight into the possible pathogenic mechanism of type 2N
VWD in Chinese patients carrying these mutations.
PMID- 24351656
TI - A controlled, comparative study of a fixed-bearing versus mobile-bearing ankle
arthroplasty.
AB - BACKGROUND: Total ankle arthroplasty is available with fixed-bearing (FB) or
mobile-bearing (MB) versions, and there is little consensus on the benefits and
drawbacks of each type. This study aimed to compare clinical outcomes of
statistically paired series of FB and MB versions of the same ankle prosthesis.
METHODS: The study was a multicenter retrospective comparison between 2 groups:
the FB group of 33 consecutive Talaris cases and the MB group of 33 "paired"
Salto cases, selected from a database of 313 consecutive cases to statistically
match etiology, age, and preoperative American Orthopaedic Foot & Ankle Society
(AOFAS) score. All patients were operated upon with the same operative technique
and received identical pre- and postoperative clinical and radiographic
assessments. The mean follow-up was 24 months for the FB group and 23 months for
the MB group. RESULTS: There was no statistical difference between results of the
2 groups in terms of accuracy of positioning, clinical and radiographic mobility,
and morbidity. The most recent postoperative AOFAS scores were higher for the FB
group than for the MB group (P = .05). Radiolucent lines were observed in 4 FB
patients versus 13 MB patients (P = .02). Subchondral cysts were noted in 1 FB
patient and in 8 MB patients (P = .01). CONCLUSION: There was no notable
difference in clinical performance of the FB and MB implants with the numbers
available. This short-term study demonstrated that FB ankle arthroplasty had
results equivalent to, if not better than, MB ankle arthroplasty. Longer follow
up is necessary to determine the success of this new generation of ankle
arthroplasty. LEVEL OF EVIDENCE: Level III, retrospective case control study.
PMID- 24351657
TI - Proximal reverse chevron metatarsal osteotomy, lateral soft tissue release, and
akin osteotomy through a single medial incision for hallux valgus.
AB - BACKGROUND: Scarring on the dorsal first web space after lateral soft tissue
release can be a major contributor to patient dissatisfaction following hallux
valgus surgery. We hypothesized that performing distal soft tissue procedure
(DSTP), proximal reverse chevron metatarsal osteotomy (PCMO), and Akin osteotomy
through a single medial incision would provide better clinical and radiographic
results with improved patient satisfaction compared with bunion corrections
performed through 2 incisions. METHODS: The study included 117 feet (of 98
patients) with moderate to severe hallux valgus. Clinically, the preoperative and
final follow-up visual analog scale (VAS) pain scores, the preoperative and final
follow-up American Orthopaedic Foot & Ankle Society (AOFAS) hallux
metatarsophalangeal (MTP)-interphalangeal (IP) scores, first MTP joint range of
motion (ROM), and patient satisfaction after the surgery were evaluated.
Radiographically, the hallux valgus angle (HVA), intermetatarsal angle (IMA),
hallux valgus interphalangeal angle (HIA), medial sesamoid position (MSP), and
first to fifth metatarsal width (1-5MTW) were analyzed before and after surgery.
RESULTS: The mean AOFAS hallux score improved from 56.3 preoperatively to 90.6 at
the final follow-up, and the mean VAS pain score decreased from 6.8
preoperatively to 1.5 at the final follow-up (P < .001). Ninety-five percent of
the patients were satisfied with the surgery. Radiographically, the mean HVA
decreased from 36.1 degrees (range, 16.0 to 44.0 degrees) preoperatively to 5.4
degrees (range, -12.4 to 29.7 degrees) at the final follow-up (P < .001), and the
mean IMA decreased from 19.0 degrees (range, 9.0 to 28.0 degrees) preoperatively
to 4.5 degrees (range, -5.0 to 14.2 degrees) at the final follow-up (P < .001).
The mean 1-5MTW also decreased by 16% (16 mm) from 97.3 mm (range, 85.0 to 110.0
mm) preoperatively to 81.3 mm (range, 70.0 to 95.0 mm) at the final follow-up (P
< .001). CONCLUSION: We achieved very favorable clinical and radiographic
outcomes with minimal complications in patients with moderate to severe hallux
valgus, by treating hallux valgus using DSTP, PCMO, and Akin osteotomy through a
single medial incision. The single medial incision scar improved the cosmetic
results by avoiding the formation of a disfiguring dorsal first web space scar.
LEVEL OF EVIDENCE: Level IV, retrospective case series.
PMID- 24351658
TI - Self-reported quality of life in patients with diabetes: a comparison of patients
with and without Charcot neuroarthropathy.
AB - BACKGROUND: Previous reports using the Short Form-36 as a generic measure of
quality of life have demonstrated reduced quality of life in patients with
Charcot neuroarthropathy (CN). The aim of this study was to assess self-reported
quality of life using the SF-36 and a region-specific assessment (the Foot and
Ankle Ability Measure [FAAM]), hypothesizing that patients with diabetes and CN
would have lower self-reported scores than patients with diabetes and no foot
disease. METHODS: Fifty patients with diabetes and CN were included in the study
group. Fifty-six patients with diabetes and no pedal complaints comprised the
control group. Quality of life was assessed with the SF-36 and the FAAM. RESULTS:
Patients with CN were more likely to have type 1 diabetes mellitus, were more
likely to use insulin, had greater duration of diabetes, and were more likely to
be neuropathic than patients in the control group. Patients with CN reported mean
FAAM activities of daily living (ADL) scores that were 2 standard deviations
below the control group and sports scores that were 1 standard deviation lower.
There was no notable difference between the SF-36 mental component summary scores
between the CN and control groups. SF-36 physical component summary scores in
patients with CN were notably lower than scores in the control group. CONCLUSION:
CN is associated with reduced quality of life as measured with the SF-36 and
FAAM. To the best of our knowledge, this is the first study directly comparing
self-reported outcome assessments in patients with both diabetes and CN and
patients with diabetes without foot complaints. LEVEL OF EVIDENCE: Level III,
comparative series.
PMID- 24351660
TI - Feasibility of endoscopic assessment and treating to target to achieve mucosal
healing in ulcerative colitis.
AB - BACKGROUND: Mucosal healing (MH) as a treatment target for ulcerative colitis is
of growing interest because it is associated with improved clinical outcomes.
However, the feasibility and probability of reaching MH in clinical practice is
unknown. We therefore evaluated the feasibility of "treating to target" according
to endoscopic findings to reach MH. METHODS: All endoscopic outcomes of patients
with ulcerative colitis followed in a single inflammatory bowel disease unit from
2011 to 2012 were reviewed and subsequent therapeutic management. Cumulative
incidence of MH and histologic healing (HH) were estimated using a Kaplan-Meier
method. RESULTS: A total of 60 patients underwent at least 2 consecutive
endoscopic assessments, of whom 45 and 48 patients had endoscopic and histologic
evidence of active disease, respectively. After a median follow-up of 76 weeks,
27 of 45 (60%) patients with endoscopic disease activity at baseline achieved MH
and 24 (50%) of 48 patients with histologic disease activity at baseline had HH.
The cumulative probabilities of MH were 26%, 52%, and 70% at 26, 52, and 76
weeks, respectively. The cumulative probabilities of HH at weeks 26, 52, and 76
from the time of initial procedure were 19%, 41%, and 57%, respectively. Any
adjustment in medical therapy in case of persistent endoscopic activity was
associated with both MH and HH. CONCLUSIONS: Repeated assessment of endoscopic
disease activity with adjustment of medical therapy to the target of MH is
feasible in clinical practice in patients with ulcerative colitis, and seems to
be of benefit.
PMID- 24351659
TI - Wolbachia interferes with the intracellular distribution of Argonaute 1 in the
dengue vector Aedes aegypti by manipulating the host microRNAs.
AB - Argonaute proteins (AGOs) are vital components of the RNA-induced silencing
complex in gene silencing. AGOs are indispensable for microRNA (miRNA) biogenesis
as well as function, and are intracellularly localized to both the cytoplasm and
the nucleus. Cytoplasmic AGO-miRNA complexes are mainly involved in cleavage or
translational repression of target mRNAs while the nuclear ones are engaged in
transcriptional gene silencing, methylation, chromatin remodeling, and splicing.
In insects, AGO1 and AGO2 are involved in RNA interference and miRNA pathways but
the components involved in their trafficking between the nucleus and the
cytoplasm are not known. In this study, we found that importin beta-4 facilitates
AGO1 distribution to the nucleus, which is regulated by aae-miR-981 miRNA. The
results also revealed association of prohibitin with AGO1 that may play an
important role in its stability. Importantly, we found that AGO1 distribution to
the nucleus is blocked by Wolbachia, an endosymbiotic bacterium introduced into
the Dengue vector, Aedes aegypti. Our results provide basic mechanisms on
intracellular trafficking of AGO1 in insects and how this may be altered by
Wolbachia, which may affect trafficking of miRNAs to the nucleus leading to
alteration in epigenetic effects.
PMID- 24351661
TI - Decoding norovirus infection in Crohn's disease.
AB - Although a causing viral infectious agent remains untraceable in Crohn's disease,
most recent genome-wide association studies have linked the FUT2 W143X mutation
(resulting in asymptomatic norovirus infection) with the pathogenesis of Crohn's
ileitis and with vitamin B12 deficiency (i.e., a known risk factor for Crohn's
disease with ileal involvement). In line with these findings, host variations in
additional genes involved in host response to norovirus infection (such as
ATG16L1 and NOD2) predispose humans to Crohn's ileitis. One may therefore presume
that asymptomatic norovirus infection may contribute to disruption of the
stability of the gut microbiota leading to Crohn's ileitis. These paradigms
highlight not only the need to revisit the potential transmissibility of Crohn's
disease, but also potential safety issues of forthcoming clinical trials on human
probiotic infusions in Crohn's ileitis by rigorous donors screening program.
PMID- 24351662
TI - Usefulness of surgical parameters as predictors of postoperative cardiac events
in patients undergoing non-cardiac surgery.
AB - BACKGROUND: Postoperative cardiac events are an important cause of morbidity and
mortality in patients undergoing non-cardiac surgery. Predictive values of
surgical parameters with respect to development of postoperative cardiac events
have not been well investigated. METHODS AND RESULTS: This study included 1,016
consecutive patients who underwent cardiac consultation prior to elective non
cardiac surgery. A major adverse cardiac event (MACE) was defined as a composite
of all-cause death, non-fatal myocardial infarction, and pulmonary edema within
30 days of surgery. There were 95 postoperative MACEs (9.4%). Patients with
postoperative MACE were significantly older, and had significantly higher revised
cardiac risk index than those without. ST-T change on electrocardiogram (ECG) was
significantly higher in patients with postoperative MACE. Of the surgical
parameters, significant differences in surgery time (317+/-211min vs. 189+/
112min, P<0.001), postoperative hemoglobin (10.7+/-1.9g/dl vs. 11.3+/-1.8g/dl,
P=0.007), risk of surgery (P<0.001), and transfusion (37.6% vs. 6.6%, P<0.001)
were observed between the 2 groups. On multivariate logistic regression analysis,
surgery time (odds ratio [OR], 1.004; 95% confidence interval [CI]: 1.003-1.006,
P<0.001) and need for transfusion (OR, 4.578; 95% CI: 2.599-8.065, P<0.001), as
well as age and ST-T change on ECG were independent predictors of postoperative
MACE. CONCLUSIONS: Surgical parameters, including surgery time and transfusion,
can strongly predict development of postoperative MACE in patients undergoing non
cardiac surgery.
PMID- 24351663
TI - SeHCAT [tauroselcholic (selenium-75) acid] for the investigation of bile acid
malabsorption and measurement of bile acid pool loss: a systematic review and
cost-effectiveness analysis.
AB - BACKGROUND: The principal diagnosis/indication for this assessment is chronic
diarrhoea due to bile acid malabsorption (BAM). Diarrhoea can be defined as the
abnormal passage of loose or liquid stools more than three times daily and/or a
daily stool weight > 200 g per day and is considered to be chronic if it persists
for more than 4 weeks. The cause of chronic diarrhoea in adults is often
difficult to ascertain and patients may undergo several investigations without a
definitive cause being identified. BAM is one of several causes of chronic
diarrhoea and results from failure to absorb bile acids (which are required for
the absorption of dietary fats and sterols in the intestine) in the distal ileum.
OBJECTIVE: For people with chronic diarrhoea with unknown cause and in people
with Crohn's disease and chronic diarrhoea with unknown cause (i.e. before
resection): (1) What are the effects of selenium-75-homocholic acid taurine
(SeHCAT) compared with no SeHCAT in terms of chronic diarrhoea, other health
outcomes and costs? (2) What are the effects of bile acid sequestrants (BASs)
compared with no BASs in people with a positive or negative SeHCAT test? (3) Does
a positive or negative SeHCAT test predict improvement in terms of chronic
diarrhoea, other health outcomes and costs? DATA SOURCES: A systematic review was
conducted to summarise the evidence on the clinical effectiveness of SeHCAT for
the assessment of BAM and the measurement of bile acid pool loss. Search
strategies were based on target condition and intervention, as recommended in the
Centre for Reviews and Dissemination (CRD) guidance for undertaking reviews in
health care and the Cochrane Handbook for Diagnostic Test Accuracy Reviews. The
following databases were searched up to April 2012: MEDLINE; MEDLINE In-Process &
Other Non-Indexed Citations; EMBASE; the Cochrane Databases; Database of
Abstracts of Reviews of Effects; Health Technology Assessment (HTA) Database; and
Science Citation Index. Research registers and conference proceedings were also
searched. REVIEW METHODS: Systematic review methods followed the principles
outlined in the CRD guidance for undertaking reviews in health care and the
National Institute for Health and Care Excellence (NICE) Diagnostic Assessment
Programme interim methods statement. In the health economic analysis, the cost
effectiveness of SeHCAT for the assessment of BAM, in patients with chronic
diarrhoea, was estimated in two different populations. The first is the
population of patients with chronic diarrhoea with unknown cause and symptoms
suggestive of diarrhoea-predominant irritable bowel syndrome (IBS-D) and the
second population concerns patients with Crohn's disease without ileal resection
with chronic diarrhoea. For each population, three models were combined: (1) a
short-term decision tree that models the diagnostic pathway and initial response
to treatment (first 6 months); (2) a long-term Markov model that estimates the
lifetime costs and effects for patients initially receiving BAS; and (3) a long
term Markov model that estimates the lifetime costs and effects for patients
initially receiving regular treatment (IBS-D treatment in the first population
and Crohn's treatment in the second population). Incremental cost-effectiveness
ratios were estimated as additional cost per additional responder in the short
term (first 6 months) and per additional quality-adjusted life-year (QALY) in the
long term (lifetime). RESULTS: We found three studies assessing the relationship
between the SeHCAT test and response to treatment with cholestyramine. However,
the studies had small numbers of patients with unknown cause chronic diarrhoea,
and they used different cut-offs to define BAM. For the short term (first 6
months), when trial of treatment is not considered as a comparator, the optimal
choice depends on the willingness to pay for an additional responder. For lower
values (between L1500 and L4600) the choice will be no SeHCAT in all scenarios;
for higher values either SeHCAT 10% or SeHCAT 15% becomes cost-effective. For the
lifetime perspective, the various scenarios showed widely differing results: in
the threshold range of L20,000-30,000 per QALY gained we found as optimal choice
either no SeHCAT, SeHCAT 5% (only IBS-D) or SeHCAT 15%. When trial of treatment
is considered a comparator, the analysis showed that for the short term, trial of
treatment is the optimal choice across a range of scenarios. For the lifetime
perspective with trial of treatment, again the various scenarios show widely
differing results. Depending on the scenario, in the threshold range of L20,000
30,000 per QALY gained, we found as optimal choice either trial of treatment, no
SeHCAT or SeHCAT 15%. CONCLUSIONS: In conclusion, the various analyses show that
for both populations considerable decision uncertainty exists and that no firm
conclusions can be formulated about which strategy is optimal. Standardisation of
the definition of a positive SeHCAT test should be the first step in assessing
the usefulness of this test. As there is no reference standard for the diagnosis
of BAM and SeHCAT testing provides a continuous measure of metabolic function,
diagnostic test accuracy (DTA) studies are not the most appropriate study design.
However, in studies where all patients are tested with SeHCAT and all patients
are treated with BASs, response to treatment can provide a surrogate reference
standard; further DTA studies of this type may provide information on the ability
of SeHCAT to predict response to BASs. A potentially more informative option
would be multivariate regression modelling of treatment response (dependent
variable), with SeHCAT result and other candidate clinical predictors as
covariates. Such a study design could also inform the definition of a positive
SeHCAT result. STUDY REGISTRATION: The study is registered as PROSPERO
CRD42012001911. FUNDING: The National Institute for Health Research Health
Technology Assessment programme.
PMID- 24351664
TI - New infection rate of bovine mammary glands after application of an internal teat
seal at dry-off.
AB - The internal teat sealant OrbeSeal(r) (Zoetis, Berlin, Germany) is intended to
prevent new intramammary infection (IMI) throughout the dry period. The aim of
this field study was to determine new infection rates in udder quarters applied
exclusively with the sealant at dry-off and untreated ones (control group). For
that, the new infection rate of udder quarters treated with the sealant was
evaluated in a split-udder design (front right and rear left udder quarters
treated, the other ones untreated) in 128 cows from nine dairy farms in North
Germany that were healthy in all four udder quarters (i.e. <100 000 cells/ml,
bacteriologically negative). After calving, duplicate quarter milk samples were
collected twice at DIM (days in milk) 5-12 and 7 d later for culture. The new
infection rates for treated and untreated groups were 3.4 and 10.5%,
respectively. The results showed that applying a standardised study design with
very few confounders under field conditions, using internal teat sealants reduced
the new infection rate on quarter level to a third of that of the control group.
Thus, internal teat sealants represent a viable option for dry-off treatment of
udder-healthy cows.
PMID- 24351665
TI - Wireless sensor networks for ambient assisted living.
AB - This paper introduces wireless sensor networks for Ambient Assisted Living as a
proof of concept. Our workgroup has developed an arrhythmia detection algorithm
that we evaluate in a closed space using a wireless sensor network to relay the
information collected to where the information can be registered, monitored and
analyzed to support medical decisions by healthcare providers. The prototype we
developed is then evaluated using the TelosB platform. The proposed architecture
considers very specific restrictions regarding the use of wireless sensor
networks in clinical situations. The seamless integration of the system
architecture enables both mobile node and network configuration, thus providing
the versatile and robust characteristics necessary for real-time applications in
medical situations. Likewise, this system architecture efficiently permits the
different components of our proposed platform to interact efficiently within the
parameters of this study.
PMID- 24351666
TI - Fault diagnosis of rotating machinery based on an adaptive ensemble empirical
mode decomposition.
AB - The vibration based signal processing technique is one of the principal tools for
diagnosing faults of rotating machinery. Empirical mode decomposition (EMD), as a
time-frequency analysis technique, has been widely used to process vibration
signals of rotating machinery. But it has the shortcoming of mode mixing in
decomposing signals. To overcome this shortcoming, ensemble empirical mode
decomposition (EEMD) was proposed accordingly. EEMD is able to reduce the mode
mixing to some extent. The performance of EEMD, however, depends on the
parameters adopted in the EEMD algorithms. In most of the studies on EEMD, the
parameters were selected artificially and subjectively. To solve the problem, a
new adaptive ensemble empirical mode decomposition method is proposed in this
paper. In the method, the sifting number is adaptively selected, and the
amplitude of the added noise changes with the signal frequency components during
the decomposition process. The simulation, the experimental and the application
results demonstrate that the adaptive EEMD provides the improved results compared
with the original EEMD in diagnosing rotating machinery.
PMID- 24351667
TI - Automatic and objective assessment of alternating tapping performance in
Parkinson's disease.
AB - This paper presents the development and evaluation of a method for enabling
quantitative and automatic scoring of alternating tapping performance of patients
with Parkinson's disease (PD). Ten healthy elderly subjects and 95 patients in
different clinical stages of PD have utilized a touch-pad handheld computer to
perform alternate tapping tests in their home environments. First, a neurologist
used a web-based system to visually assess impairments in four tapping dimensions
('speed', 'accuracy', 'fatigue' and 'arrhythmia') and a global tapping severity
(GTS). Second, tapping signals were processed with time series analysis and
statistical methods to derive 24 quantitative parameters. Third, principal
component analysis was used to reduce the dimensions of these parameters and to
obtain scores for the four dimensions. Finally, a logistic regression classifier
was trained using a 10-fold stratified cross-validation to map the reduced
parameters to the corresponding visually assessed GTS scores. Results showed that
the computed scores correlated well to visually assessed scores and were
significantly different across Unified Parkinson's Disease Rating Scale scores of
upper limb motor performance. In addition, they had good internal consistency,
had good ability to discriminate between healthy elderly and patients in
different disease stages, had good sensitivity to treatment interventions and
could reflect the natural disease progression over time. In conclusion, the
automatic method can be useful to objectively assess the tapping performance of
PD patients and can be included in telemedicine tools for remote monitoring of
tapping.
PMID- 24351669
TI - Interpretation of magnetoelectric phase states using the praphase concept and
exchange symmetry.
AB - The majority of magnetoelectric crystals show complex temperature-magnetic field
or temperature-pressure phase diagrams with alternating antiferromagnetic
incommensurate, magnetoelectric, and commensurate phases. Such phase diagrams
occur as a result of successive magnetic instabilities with respect to different
order parameters, which usually transform according to different irreducible
representations (IRs) of the space group of the crystal. Therefore, in order to
build a phenomenological theory of phase transitions in such magnetoelectrics one
has to employ several order parameters and assume the proximity of various
instabilities on the thermodynamic path. In this work we analyze the
magnetoelectrics MnWO4, CuO, NaFeSi2O6, NaFeGe2O6, Cu3Nb2O8, alpha-CaCr2O4 and
FeTe2O5Br using the praphase concept and the symmetry of the exchange
Hamiltonian. We find that in all the considered cases the appearing magnetic
structures are described by IRs entering into a single exchange multiplet,
whereas in the cases of MnWO4 and CuO by a single IR of the space group of the
praphase structure. Therefore, one can interpret the complex phase diagrams of
magnetoelectrics as induced by a single IR either of the praphase or of the
symmetry group of the exchange Hamiltonian. Detailed temperature-magnetic field
phase diagrams of MnWO4 and CuO for certain field directions are obtained and the
magnetic structures of the field-induced phases are determined.
PMID- 24351671
TI - Surrogates of long-term vitamin d exposure and ovarian cancer risk in two
prospective cohort studies.
AB - Experimental evidence and ecologic studies suggest a protective role of vitamin D
in ovarian carcinogenesis. However, epidemiologic studies using individual level
data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D
intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term
surrogates of vitamin D exposure within the Nurses' Health Study (NHS) and NHSII.
We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for
risk of overall ovarian cancer and by histologic subtype using Cox proportional
hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we
identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970,
NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B
exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but
was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67;
95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B
flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01),
but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders,
ovarian cancer risk was not associated with vitamin D intake from food or
supplements or with predicted 25(OH)D levels. Our study does not strongly support
a protective role for vitamin D in ovarian cancer risk.
PMID- 24351672
TI - The clinical potential of circulating tumor cells; the need to incorporate a
modern "immunological cocktail" in the assay.
AB - The accepted clinical assay, CellSearch(r), and lab-on-a-chip tests for capturing
circulating tumor cells are antibody-mediated. Attempts to improve their
sensitivity have relied upon physical changes in the instruments. There have been
no significant advances in improving the antibody-mediated portion of the
capture. Modern immunologic engineering offers major possibilities for improving
the sensitivity and other features of the assay. These include obtaining
univalent antibody fragments such as scFvs with picomolar binding affinity and
sufficient specificity; altering them to enhance their range of potential contact
with target antigens; using antibodies directed against different epitopes on
epithelial, mesenchymal or organ-specific cell surface markers to allow
simultaneous binding and investigating non-antibody binding molecules as
substitutes for antibody. These maneuvers could markedly improve the ability of
current assays to improve patient care and might result in an acceptable test for
detecting cancer earlier in high risk patients.
PMID- 24351670
TI - Exosomes in prostate cancer: putting together the pieces of a puzzle.
AB - Exosomes have been shown to act as mediators for cell to cell communication and
as a potential source of biomarkers for many diseases, including prostate cancer.
Exosomes are nanosized vesicles secreted by cells and consist of proteins
normally found in multivesicular bodies, RNA, DNA and lipids. As a potential
source of biomarkers, exosomes have attracted considerable attention, as their
protein content resembles that of their cells of origin, even though it is noted
that the proteins, miRNAs and lipids found in the exosomes are not a reflective
stoichiometric sampling of the contents from the parent cells. While the
biogenesis of exosomes in dendritic cells and platelets has been extensively
characterized, much less is known about the biogenesis of exosomes in cancer
cells. An understanding of the processes involved in prostate cancer will help to
further elucidate the role of exosomes and other extracellular vesicles in
prostate cancer progression and metastasis. There are few methodologies available
for general isolation of exosomes, however validation of those methodologies is
necessary to study the role of exosomal-derived biomarkers in various diseases.
In this review, we discuss "exosomes" as a member of the family of extracellular
vesicles and their potential to provide candidate biomarkers for prostate cancer.
PMID- 24351673
TI - Ketogenic diets for weight loss: A review of their principles, safety and
efficacy.
AB - SUMMARY: Low-carbohydrate "ketogenic" diets have increased in popularity over
recent years as a means of weight loss. Published studies of these diets have
been highly heterogeneous, and it remains unclear to what degree dietary
carbohydrate intake must be restricted in order to induce ketosis. Despite
concern that they are often relatively high in fat, ketogenic low-carbohydrate
diets have been generally shown to compare favourably with low-fat diets in terms
of weight loss and improvements in triglyceride and high-density lipoprotein
levels. This review includes a brief overview of ketone body metabolism, and
summarises the literature regarding the safety and efficacy of ketogenic diets
for weight loss.:
PMID- 24351674
TI - The Counterweight programme: Prevalence of CVD risk factors by body mass index
and the impact of 10% weight change.
AB - SUMMARY: OBJECTIVES: To examine relationships between body mass index (BMI),
prevalence of physician-recorded cardiovascular disease (CVD) risk factors in
primary care, and changes in risk with 10% weight change. METHODS: The
Counterweight Project conducted a baseline cross-sectional survey of medical
records of 6150 obese (BMI >= 30 kg/m(2)), 1150 age- and sex-matched overweight
(BMI 25 to <30 kg/m(2)), and 1150 age- and sex-matched normal weight (BMI 18.5 to
<25 kg/m(2)) controls, in primary care. Data were collected for the previous 18
months to examine BMI and disease prevalence, and then modelled to show the
potential effect of 10% weight loss or gain on risk. RESULTS: Obese patients
develop more CVD risk factors than normal weight controls. BMI >= 40 kg/m(2)
exhibits increased prevalence of type 2 diabetes mellitus (DM), odds ratio (OR)
men: 6.16 (p < 0.001); women: 7.82 (p < 0.001) and hypertension OR men: 5.51 (p <
0.001); women: 4.16 (p < 0.001). Dyslipidaemia peaked around BMI 35 to <37.5
kg/m(2), OR men: 3.26 (p < 0.001); women 3.76 (p < 0.001) and CVD at BMI 37.5 to
<40 kg/m(2) in men, OR 4.48 (p < 0.001) and BMI >= 40 kg/m(2) in women, OR 3.98
(p < 0.001). A 10% weight loss from the sample mean of 32.5 kg/m(2) reduced the
OR for type 2 DM by 30% and CVD by 20%, while 10% weight gain increased type 2 DM
risk by more than 35% and CVD by 20%. CONCLUSION: Obesity plays a fundamental
role in CVD risk, which is reduced with weight loss. Weight management
intervention strategies should be a public health priority to reduce the burden
of disease in the population.
PMID- 24351675
TI - The possible influence of osteoarthritis of the knee on the accumulation of
coronary risk factors in postmenopausal obese women.
AB - SUMMARY: OBJECTIVE: This cross-sectional study was designed to clarify the
association between osteoarthritis of the knee (OAK) and coronary risk factors in
postmenopausal obese women. SUBJECTS: The subjects consisted of 72 postmenopausal
obese women (mean age 60.3 +/- 7.6 years) with coronary risk factors. They were
divided into two groups; including the OAK group and the normal knee (control)
group. METHODS: Aerobic capacity was evaluated by maximal oxygen uptake (VO2 max)
estimated from the nomogram of Astrand and Ryhming. Daily activity was measured
by a single-axis accelerometer. RESULTS: After adjusting for the age, the OAK
group (n = 37) showed significantly higher obesity indices, the number of
coronary risk factors, incidence of Metabolic Syndrome, a lower aerobic capacity
and a lower daily activity than control group (n = 35). After adjusting for the
age, body weight and body mass index, the OAK group with a high waist
circumference, a low VO2 max and low mean total energy expenditure showed a
significantly higher number of coronary risk factors than the control group with
a low waist circumference, high VO2 max and high total energy expenditure.
CONCLUSION: These results suggest that OAK was therefore associated with the
aerobic capacity, daily activity and Metabolic Syndrome, and it may indirectly
influence for the development of the future coronary heart disease in
postmenopausal obese women.
PMID- 24351676
TI - Obesity in Tonga: A cross-sectional comparative study of perceptions of body size
and beliefs about obesity in lay people and nurses.
AB - SUMMARY: BACKGROUND: Obesity is a major public health issue in Tonga, where
prevalence is significantly higher than in Europe and North America. Obesity and
its health-related complications are likely to increase as a result of western
influences on diet and lifestyle. The aim of this study was to investigate
perceptions of body size in Tongan lay people and nurses, and their beliefs about
the causes of obesity and its consequences for health. METHODS: A cross-sectional
comparative study was conducted. Medical and surgical inpatients and outpatients
were recruited from Vaiola Hospital in Tonga, over a 4 week period. Hospital
nurses were included for comparison. Overall, 73 lay public and 34 nurses
completed questionnaires about their beliefs about obesity, perceptions of their
own body size and the health conditions associated with obesity. Subjects were
also weighed and measured for calculating body mass index (BMI). RESULTS: Both
Tongan lay people and nurses underestimated their body weight and size, although
the degree of underestimation was more marked in the lay group. The more accurate
perception of body size in nurses may reflect their greater understanding of the
health consequences of obesity. CONCLUSIONS: This study has provided some insight
into how obesity is viewed in Tonga, in particular differences between lay people
and nurses in their own perception of weight, beliefs about obese people and the
health consequences of obesity. Future research should aim to explore Tongans
views of the health consequences of obesity as well as their perceptions of how
serious these consequences are.
PMID- 24351677
TI - Acanthosis Nigricans and insulin levels in a south Indian population-(ADEPS paper
2).
AB - SUMMARY: OBJECTIVE: Aim of the study was to determine the prevalence of
Acanthosis Nigricans (AN) in a central Kerala south Indian population and to
evaluate its correlations with diabetes, obesity, insulin levels and other
factors. METHODS: A cross-sectional community survey including physical
examination and biochemical evaluation was conducted among adults above the age
of 18 years in central Kerala In the first phase of the study 3069 participants
were surveyed using questionnaires regarding socioeconomic status and medical
details. Among them 986 subjects were evaluated in the second phase of the study
which included anthropometric measurements, examination for blood pressure and
Acanthosis Nigricans, blood tests such as blood glucose, fasting lipids. Fasting
serum insulin level was measured for all non-diabetic subjects. Statistical
analysis was done using SPSS 11.0 version software. RESULTS: RESULTS of the study
showed that 16.1% of population had AN and it was significantly higher among
females (19.6%) than males (11.4%). Prevalence of AN was highest in 30-40 year
age group and it decreased with the age. Prevalence of AN correlated positively
with female gender, obesity, high triglyceride levels and presence of diabetes.
Presence of AN was significantly associated with higher fasting insulin levels.
Males with AN had significantly higher insulin values than females with AN.
CONCLUSION: AN has stronger clinical relevance among males than females and it
can be used as a marker of insulin resistance in south Indian population
especially if obesity and family history of diabetes are also present.
PMID- 24351678
TI - Severe obesity: Investigating the socio-demographics within the extremes of body
mass index.
AB - SUMMARY: OBJECTIVE: To examine the trends in the prevalence of classes I, II and
III obesity between 1991 and 2006 among the South Australian adult population. In
addition, to explore the association of severe (class II and III) obesity with a
range of socio-demographics, chronic conditions and risk factor variables.
METHOD: Trends of self-reported obesity prevalence were examined using
representative, annual, face-to-face South Australian Health Omnibus Surveys from
1991 to 2006 (n ~ 3000 per year). Biomedical data, including measured height and
weight, were collected in the North West Adelaide Health (cohort) Study (NWAHS),
a representative random adult sample selected from the electronic white pages
(EWP) (n = 4060). RESULTS: The age standardised prevalence of self-reported class
II and III obesity among those aged 18 years and over increased from 2.4% in 1991
to 8.1% in 2006. The greatest relative percentage increase over this time was
seen amongst those with class III obesity (452.3%). Using biomedical data,
multivariate analysis results indicated that among those who were obese, women
were more than two and a half times more likely than men to be of class II and
III. Among those who were obese, those aged 20-54 years and living in the
low/lowest quintiles of Socioeconomic Indexes for Areas, Index of Relative
Socioeconomic Disadvantage (SEIFA IRSD) were statistically significantly more
likely to be class II or III obese when compared to those in the highest
categories. CONCLUSION: The prevalence of class II and III obesity increased
significantly between 1991 and 2006. The socio-demographics of those who are
class II and III obesity are different from those that are normally described for
obesity as a whole especially in regard to the younger age cohort. The current
prevalence of severe obesity within Australia is probably underestimated and
these results highlight the need to address this sub-group of the population.
PMID- 24351679
TI - Association between overweight and dip osteoarthritis among middle-aged Finnish
female dentists and teachers.
AB - SUMMARY: The objective of this study was to examine associations between body
mass index (BMI) and symptomatic and non-symptomatic radiographic osteoarthritis
in the distal interphalangeal joints (DIP ROA). The subjects were 295 female
dentists and 248 female teachers aged 45-63 years randomly selected from the
registers of the Finnish Dental Association and the Finnish Teachers' Trade Union
of the Helsinki metropolitan region. Radiographs of both hands were examined for
the presence of osteoarthritis in each DIP joint. Information on the occurrence
of pain in each DIP joint during the past 30 days and hand laterality was
obtained by questionnaire. Current BMI was based on self-reported height and
measured weight. BMI at the age of 25 years was based on self-reported height and
weight. Overweight was defined as BMI >= 25.0 kg/m(2). Allowing for age,
occupation, hand-loading leisure-time physical activity and smoking history, the
risk of symptomatic DIP ROA was increased in currently overweight women (OR 1.98,
95% CI 1.18-3.34) and in women with overweight both currently and at the age of
25 (7.55; 1.33-42.83). The OR for an increase of one standard deviation in BMI at
the age of 25 was 1.20 (1.05-1.38) and that for a similar increase in current BMI
1.08 (1.01-1.16), adjusted as above. No relationship of BMI with non-symptomatic
DIP ROA or joint pain only was found. The study provides evidence that the risk
of symptomatic DIP ROA is increased among overweight middle-aged women.
Consideration even of BMI at young adulthood further underlines the association.:
PMID- 24351680
TI - The Trp64Arg of beta3-adrenergic receptor gene and prediction of weight regain in
obese female.
PMID- 24351681
TI - TCEB3C a putative tumor suppressor gene of small intestinal neuroendocrine
tumors.
AB - Small intestinal neuroendocrine tumors (SI-NETs), formerly known as midgut
carcinoids, are rare and slow-growing neoplasms. Frequent loss of one copy of
chromosome 18 in primary tumors and metastases has been observed. The aim of the
study was to investigate a possible role of TCEB3C (Elongin A3), currently the
only imprinted gene on chromosome 18, as a tumor suppressor gene in SI-NETs, and
whether its expression is epigenetically regulated. Primary tumors, metastases,
the human SI-NET cell line CNDT2.5, and two other cell lines were included.
Immunohistochemistry, gene copy number determination by PCR, colony formation
assay, western blotting, real-time quantitative RT-PCR, RNA interference, and
quantitative CpG methylation analysis by pyrosequencing were performed. A large
majority of tumors (33/43) showed very low to undetectable Elongin A3 expression
and as expected 89% (40/45) displayed one gene copy of TCEB3C. The DNA
hypomethylating agent 5-aza-2'-deoxycytidine induced TCEB3C expression in CNDT2.5
cells, in primary SI-NET cells prepared directly after surgery, but not in two
other cell lines. Also siRNA to DNMT1 and treatment with the general histone
methyltransferase inhibitor 3-deazaneplanocin A induced TCEB3C expression in a
cell type-specific way. CpG methylation at the TCEB3C promoter was observed in
all analyzed tissues and thus not related to expression. Overexpression of TCEB3C
resulted in a 50% decrease in clonogenic survival of CNDT2.5 cells, but not of
control cells. The results support a putative role of TCEB3C as a tumor
suppressor gene in SI-NETs. Epigenetic repression of TCEB3C seems to be tumor
cell type-specific and involves both DNA and histone methylation.
PMID- 24351682
TI - Evaluating digestive neuroendocrine tumor progression and therapeutic responses
in the era of targeted therapies: state of the art.
AB - Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous
rare tumors. They are often slow-growing and patients can have very long
survival, even at the metastatic stage. The evaluation of tumor progression and
therapeutic responses is currently based on Response Evaluation Criteria In Solid
Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are
being reexamined for NETs in the era of targeted therapies because tumor response
to targeted therapies is rarely associated with shrinkage, as opposed to
prolonged progression-free survival. Therefore, size-based criteria no longer
seem to be suitable to the assessment of NET progression and therapeutic
responses, especially considering targeted therapies. New imaging criteria,
combining morphological and functional techniques, have proven relevant for other
malignancies treated with targeted therapies. To date, such studies have rarely
been conducted on NETs. Moreover, optimizing the management of NET patients also
requires considering clinical, biological, and pathological aspects of tumor
evolution. Our objectives herein were to comprehensively review current knowledge
on the assessment of tumor progression and early prediction of therapeutic
responses and to broaden the outlook on well-differentiated NETs, in the era of
targeted therapies.
PMID- 24351683
TI - A model-based method for the design of intermittent pneumatic compression systems
acting on humans.
AB - Intermittent pneumatic compression is a well-known technique, which can be used
for several therapeutic treatments like sports recovery, lymphoedema drainage,
deep vein thrombosis prevention or others, which may require very different
operating characteristics as regards the desired pressure values and the
operating velocity. The performance and the effectiveness of the device are often
difficult to predict and must be usually optimized through empirical adjustments.
This article presents a general method based on the mathematical modelling of a
generic IPC system, aimed at studying and developing such a device with physical
and dynamical characteristics suitable for the intended application.
PMID- 24351684
TI - MicroRNA319a-targeted Brassica rapa ssp. pekinensis TCP genes modulate head shape
in chinese cabbage by differential cell division arrest in leaf regions.
AB - Leafy heads of cabbage (Brassica oleracea), Chinese cabbage (Brassica rapa), and
lettuce (Lactuca sativa) are composed of extremely incurved leaves. The shape of
these heads often dictates the quality, and thus the commercial value, of these
crops. Using quantitative trait locus mapping of head traits within a population
of 150 recombinant inbred lines of Chinese cabbage, we investigated the
relationship between expression levels of microRNA-targeted Brassica rapa ssp.
pekinensis TEOSINTE BRANCHED1, cycloidea, and PCF transcription factor4 (BrpTCP4)
genes and head shape. Here, we demonstrate that a cylindrical head shape is
associated with relatively low BrpTCP4-1 expression, whereas a round head shape
is associated with high BrpTCP4-1 expression. In the round-type Chinese cabbage,
microRNA319 (miR319) accumulation and BrpTCP4-1 expression decrease from the
apical to central regions of leaves. Overexpression of BrpMIR319a2 reduced the
expression levels of BrpTCP4 and resulted in an even distribution of BrpTCP4
transcripts within all leaf regions. Changes in temporal and spatial patterns of
BrpTCP4 expression appear to be associated with excess growth of both apical and
interveinal regions, straightened leaf tips, and a transition from the round to
the cylindrical head shape. These results suggest that the miR319a-targeted
BrpTCP gene regulates the round shape of leafy heads via differential cell
division arrest in leaf regions. Therefore, the manipulation of miR319a and
BrpTCP4 genes is a potentially important tool for use in the genetic improvement
of head shape in these crops.
PMID- 24351685
TI - The potato tuber mitochondrial proteome.
AB - Mitochondria are called the powerhouses of the cell. To better understand the
role of mitochondria in maintaining and regulating metabolism in storage tissues,
highly purified mitochondria were isolated from dormant potato tubers (Solanum
tuberosum 'Folva') and their proteome investigated. Proteins were resolved by one
dimensional gel electrophoresis, and tryptic peptides were extracted from gel
slices and analyzed by liquid chromatography-tandem mass spectrometry using an
Orbitrap XL. Using four different search programs, a total of 1,060 nonredundant
proteins were identified in a quantitative manner using normalized spectral
counts including as many as 5-fold more "extreme" proteins (low mass, high
isoelectric point, hydrophobic) than previous mitochondrial proteome studies. We
estimate that this compendium of proteins represents a high coverage of the
potato tuber mitochondrial proteome (possibly as high as 85%). The dynamic range
of protein expression spanned 1,800-fold and included nearly all components of
the electron transport chain, tricarboxylic acid cycle, and protein import
apparatus. Additionally, we identified 71 pentatricopeptide repeat proteins, 29
membrane carriers/transporters, a number of new proteins involved in coenzyme
biosynthesis and iron metabolism, the pyruvate dehydrogenase kinase, and a type
2C protein phosphatase that may catalyze the dephosphorylation of the pyruvate
dehydrogenase complex. Systematic analysis of prominent posttranslational
modifications revealed that more than 50% of the identified proteins harbor at
least one modification. The most prominently observed class of posttranslational
modifications was oxidative modifications. This study reveals approximately 500
new or previously unconfirmed plant mitochondrial proteins and outlines a facile
strategy for unbiased, near-comprehensive identification of mitochondrial
proteins and their modified forms.
PMID- 24351686
TI - Sterol-dependent induction of plant defense responses by a microbe-associated
molecular pattern from Trichoderma viride.
AB - Plant-microbe interactions involve numerous regulatory systems essential for
plant defense against pathogens. An ethylene-inducing xylanase (Eix) of
Trichoderma viride is a potent elicitor of plant defense responses in specific
cultivars of tobacco (Nicotiana tabacum) and tomato (Solanum lycopersicum). We
demonstrate that tomato cyclopropyl isomerase (SlCPI), an enzyme involved in
sterol biosynthesis, interacts with the LeEix2 receptor. Moreover, we examined
the role of SlCPI in signaling during the LeEix/Eix defense response. We found
that SlCPI is an important factor in the regulation of the induction of defense
responses such as the hypersensitive response, ethylene biosynthesis, and the
induction of pathogenesis-related protein expression in the case of LeEix/Eix.
Our results also suggest that changes in the sterol composition reduce LeEix
internalization, thereby attenuating the induction of plant defense responses.
PMID- 24351687
TI - A carbon-nitrogen lyase from Leucaena leucocephala catalyzes the first step of
mimosine degradation.
AB - The tree legume Leucaena leucocephala contains a large amount of a toxic
nonprotein aromatic amino acid, mimosine, and also an enzyme, mimosinase, for
mimosine degradation. In this study, we isolated a 1,520-bp complementary DNA
(cDNA) for mimosinase from L. leucocephala and characterized the encoded enzyme
for mimosine-degrading activity. The deduced amino acid sequence of the coding
region of the cDNA was predicted to have a chloroplast transit peptide. The
nucleotide sequence, excluding the sequence for the chloroplast transit peptide,
was codon optimized and expressed in Escherichia coli. The purified recombinant
enzyme was used in mimosine degradation assays, and the chromatogram of the major
product was found to be identical to that of 3-hydroxy-4-pyridone (3H4P), which
was further verified by electrospray ionization-tandem mass spectrometry. The
enzyme activity requires pyridoxal 5'-phosphate but not alpha-keto acid;
therefore, the enzyme is not an aminotransferase. In addition to 3H4P, we also
identified pyruvate and ammonia as other degradation products. The dependence of
the enzyme on pyridoxal 5'-phosphate and the production of 3H4P with the release
of ammonia indicate that it is a carbon-nitrogen lyase. It was found to be highly
efficient and specific in catalyzing mimosine degradation, with apparent Km and
Vmax values of 1.16*10(-4) m and 5.05*10(-5) mol s(-1) mg(-1), respectively. The
presence of other aromatic amino acids, including l-tyrosine, l-phenylalanine,
and l-tryptophan, in the reaction did not show any competitive inhibition. The
isolation of the mimosinase cDNA and the biochemical characterization of the
recombinant enzyme will be useful in developing transgenic L. leucocephala with
reduced mimosine content in the future.
PMID- 24351689
TI - Mothers' reports on systemic signs and symptoms associated with teething.
AB - PURPOSE: The purpose of this study was to compare mothers' actual observations of
signs and symptoms associated with the eruption of primary incisors in their
infants with their own recollections of the same period after eruption was
completed. METHODS: A comparative study was carried out with 45 non
institutionalized infants and their mothers. Oral clinical exams were performed
daily for detection of tooth eruption. The mothers were also interviewed daily
about signs and symptoms they thought were associated with teething in the
previous 24 hours. One week after the data collection was done, the mothers
answered the same questionnaire. Descriptive analysis and the McNemar test
(P<.05) were performed. RESULTS: Statistically significant differences were found
between the prospective and retrospective studies. Increased salivation (P<.04)
and runny nose (P<.001) were reported less often and fever was reported more
often (P<.001) in the retrospective evaluation. CONCLUSIONS: Mothers reported
similar manifestations of sleep disturbance, diarrhea, loss of appetite, and
irritability in the prospective and retrospective studies. Increased salivation
and runny nose were more frequently reported in the prospective study, whereas
fever was reported 5 times more often in the retrospective study.
PMID- 24351688
TI - MicroRNA156: a potential graft-transmissible microRNA that modulates plant
architecture and tuberization in Solanum tuberosum ssp. andigena.
AB - MicroRNA156 (miR156) functions in maintaining the juvenile phase in plants.
However, the mobility of this microRNA has not been demonstrated. So far, only
three microRNAs, miR399, miR395, and miR172, have been shown to be mobile. We
demonstrate here that miR156 is a potential graft-transmissible signal that
affects plant architecture and tuberization in potato (Solanum tuberosum). Under
tuber-noninductive (long-day) conditions, miR156 shows higher abundance in leaves
and stems, whereas an increase in abundance of miR156 has been observed in
stolons under tuber-inductive (short-day) conditions, indicative of a
photoperiodic control. Detection of miR156 in phloem cells of wild-type plants
and mobility assays in heterografts suggest that miR156 is a graft-transmissible
signal. This movement was correlated with changes in leaf morphology and longer
trichomes in leaves. Overexpression of miR156 in potato caused a drastic
phenotype resulting in altered plant architecture and reduced tuber yield. miR156
overexpression plants also exhibited altered levels of cytokinin and
strigolactone along with increased levels of LONELY GUY1 and StCyclin D3.1
transcripts as compared with wild-type plants. RNA ligase-mediated rapid
amplification of complementary DNA ends analysis validated SQUAMOSA PROMOTER
BINDING-LIKE3 (StSPL3), StSPL6, StSPL9, StSPL13, and StLIGULELESS1 as targets of
miR156. Gel-shift assays indicate the regulation of miR172 by miR156 through
StSPL9. miR156-resistant SPL9 overexpression lines exhibited increased miR172
levels under a short-day photoperiod, supporting miR172 regulation via the miR156
SPL9 module. Overall, our results strongly suggest that miR156 is a phloem-mobile
signal regulating potato development.
PMID- 24351690
TI - Factors associated with number of erupted primary teeth in Brazilian children: a
cross-sectional study.
AB - PURPOSE: The purpose of this study was to determine whether nutritional status,
gender, weight, and height affected the number of erupted primary teeth in six-
to 30 month-old children. METHODS: A cross-sectional study was carried out
involving an oral clinical examination, and weight and height measurements of 232
children, as well as a questionnaire filled out by their parents. Statistical
analysis involved descriptive data, Spearman's correlation coefficient, Kruskall
Wallis test, and multiple linear regression in two sets, using the enter method
to control the confounding factor (age) and the stepwise method for gender,
weight, and height ( P<.05). The calculation of effect size proposed by Cohen was
used to test the clinical significance of the findings. RESULTS: The number of
erupted teeth was not significantly influenced by nutritional status ( P<.58;
Kruskal-Wallis test) or gender ( P=.95; Mann-Whitney test). Body weight had a
statistically significant association with the number of erupted primary teeth (
P<.001), and height showed a positive correlation with this variable, both
independently of the child's age. CONCLUSION: The number of erupted primary teeth
was affected by weight in children of the same age.
PMID- 24351691
TI - Relationship between adjusted body mass index percentile and decayed, missing,
and filled primary teeth.
AB - PURPOSE: The purpose of this study was to determine if there was a significant
relationship between adjusted body mass index (BMI) percentiles and the frequency
of decayed, missing, and filled primary teeth (dmft) in a retrospective cohort of
3- to 5-year-old children. METHODS: Data was collected from 215 3- to 5-year old
children with an American Society of Anesthesiologists class I or II physical
status who had received dental treatment under general anesthesia at a university
hospital between 2007 and 2008. The diagnosis of dental caries and dmft scores
were confirmed by oral and radiographic examination. RESULTS: BMI percentile was
a statistically significant explanatory variable for dmft after controlling for
race, gender, and age ( P<.001). When BMI percentile increased by 10 units, the
dmft score increased by an estimated 1.1 after adjusting for the other
covariates. CONCLUSIONS: Young children with elevated BMI percentiles who have
caries may be at risk for an increased number of carious teeth in the future.
Providing nutritional and weight counseling may potentially lower the risk for
dental caries in young children while improving their general health.
PMID- 24351692
TI - Pulse granuloma as a complication following dental trauma in children.
AB - Contamination and subsequent retention of foreign bodies within wound surfaces
may negatively influence healing following maxillofacial injuries. Larger foreign
bodies that produce embedded or impalement injuries of soft tissues are easily
detected. However, smaller contaminants, such as sand, gravel, food particles,
wood splinters, and glass fibers, may not be easily identified in the initial
examination, and their remnants may remain within the injury site even after
debridement. Tissue reactions depend on the host response, type of foreign body,
and nature of the wound surface. The purposes of this report are to: (1) detail
the diagnosis and management of a peripheral pulse granuloma following retention
of food particles within gingival sulci during a dental injury; and (2) provide a
brief review of the diagnosis of foreign body-induced granulomas following
maxillofacial injuries in children.
PMID- 24351693
TI - A randomized trial of mineral trioxide aggregate cements in primary tooth
pulpotomies.
AB - PURPOSE: The purpose of this study was to compare the outcome of primary tooth
pulpotomies using two different white mineral trioxide aggregate (MTA) cements
and calcium hydroxide (CH). METHODS: Primary molars (N=139) from three- to nine
year-old children were randomly assigned to be treated using either ProRoot MTA
(N=46), MTA Angelus (N=45), or CH paste (N=48) as pulpotomy medicaments. All
pulpotomized teeth received a Class I amalgam as a final restoration. Recall
examinations were carried out at one, three, six, 12, 18, and 24 months. RESULTS:
The 24-month cumulative clinical success rates for ProRoot MTA, MTA Angelus, and
CH were approximately 98 percent, 96 percent, and 77 percent, respectively. The
cumulative radiographic success rates for ProRoot MTA, MTA Angelus, and CH were
approximately 98 percent, 91 percent, and 45 percent, respectively. For all
parameters evaluated, the MTA cements showed similar clinical and radiographic
outcomes (P>.05), which were significantly better than those of CH (P<.05). The
two-year clinical and radiographic survival probabilities for ProRoot MTA and MTA
Angelus were comparable (P=.62 and P=.20, respectively) and superior to calcium
hydroxide (all P>.05). CONCLUSIONS: ProRoot MTA and MTA Angelus showed similar
and favorable success rates as pulpotomy materials in primary molars.
PMID- 24351695
TI - Pulp therapy in pediatric patients with congenital heart disease: survey of
American Academy of Pediatric Dentistry members.
AB - PURPOSE: The purpose of this study was to identify treatment options recommended
by American Academy of Pediatric Dentistry (AAPD) members concerning pulp
treatment in primary teeth in pediatric patients with congenital heart disease
(CHD). METHODS: A web-based survey was sent to all active members of the AAPD.
The survey contained radiographs of pulpally involved primary teeth, a
description of associated signs/symptoms, and a medical history of the patient
who was positive for a type of CHD. Pediatric dentists were requested to report
treatment recommendations. RESULTS: Of the 6,590 surveys sent, 1,493 surveys
(23%) were completed. Most respondents preferred to extract the tooth with the
clinical presentation of irreversible pulpitis followed by distal shoe space
maintenance when the patient presented with a negative medical history. By
contrast, approximately half of the respondents elected to extract this tooth
without space maintenance for all of the cardiac conditions. By contrast, most
respondents elected to perform a pulpotomy in the case of reversible pulpitis
regardless of the medical history. Indirect or direct pulp therapy were the least
chosen options for both presentations. CONCLUSIONS: The presence of CHD affects
treatment decisions in teeth exhibiting irreversible pulpitis with symptomatic
apical periodontitis but not in teeth displaying reversible pulpitis with a
normal periodontal status.
PMID- 24351694
TI - Efficacy and safety of midazolam for sedation in pediatric dentistry: a
controlled clinical trial.
AB - PURPOSE: Pharmacological management of uncooperative children is becoming
increasingly common in the dental setting. The purpose of this study was to
determine the efficacy and safety of 3 different doses of midazolam for sedation
in 2- to 4- year-old children with multiple dental needs and negative behavior.
METHODS: Ten children participated in this crossover, controlled, double-blinded
clinical trial, which evaluated their behavior, appointment length and patient
response after administration of 3 different doses of midazolam or placebo.
Oxygen saturation, heart rate, respiratory rate, and blood pressure were
monitored in all sessions. RESULTS: Sedated children exhibited a more positive
behavior compared to the placebo group, both at the beginning of the appointment
(sitting in the chair) and during administration of local anesthesia (P=.008 and
P<.03, respectively). The use of midazolam allowed for longer appointments, and
doses of at least 0.3 mg/kg produced a higher rate of positive behavior overall.
No changes in oxygen saturation, heart rate, respiratory rate, and blood pressure
were observed. CONCLUSION: Midazolam was effective and safe for pediatric
sedation in the dosages studied.
PMID- 24351696
TI - Langerhans cell histocytosis of the mandible in a pediatric patient.
AB - Langerhans cell histiocytosis (LCH) is a rare, proliferative disorder in which
the accumulation of pathologic Langerhans cells leads to local tissue
infiltration and destruction. In this article, a review of LCH is presented and a
case of a single LCH lesion affecting the mandible of healthy infant is
discussed. The history, radiological appearance, histopathology and treatment
options are discussed.
PMID- 24351697
TI - Growth hormone insensitivity syndrome: unusual oral manifestations.
AB - Children with significant growth retardation and normal levels of growth hormone
are diagnosed with growth hormone insensitivity. The main oral findings observed
in patients with growth hormone insensitivity syndrome (GHIS) are underdeveloped
jaws, crowded teeth and delayed eruption of permanent teeth. This manuscript
describes a 9-year-old child diagnosed with GHIS, who had delayed eruption of
permanent teeth and 14 unerupted supernumerary teeth. All supernumerary teeth
were extracted except for two maxillary and one mandibular teeth which were
difficult to identify and access. Multiple supernumerary teeth have never been
reported before in patients with GHIS.
PMID- 24351699
TI - Co-sleeping and childhood enuresis in China.
AB - OBJECTIVE: Co-sleeping is associated with disturbance of the natural sleep
pattern, including sleep fragmentation and daytime sleepiness. Nocturnal enuresis
(NE) or bed-wetting, although benign, is a significant cause of distress to
affected children and their caregiver(s). This study investigated the
relationship between co-sleeping and NE in primary school children from China.
METHODS: Data from a previous sleep study of primary school children from 8
cities across China were analyzed. Multivariable regression analysis was
performed to assess the relationship between co-sleeping and NE while controlling
for a number of confounding factors. The prevalence of NE in co-sleeping and non
co-sleeping children in different age groups was evaluated. RESULTS: The
prevalence of co-sleeping and NE in children aged 5 to 12 years was 22.8% and
4.6%, respectively. Co-sleeping was associated with a higher prevalence of NE in
primary school age children (odds ratio [OR], 1.50; 95% confidence interval [CI],
1.27-1.77; p < .001) after adjusting for confounding factors. The differences in
the prevalence of NE between co-sleepers and non-co-sleepers were significant in
the 9-year age group (OR, 1.49; 95% CI, 1.06-2.11; p = .025) and 11- to 12-year
age group (OR, 3.16; 95% CI, 2.19-4.57; p < .001). CONCLUSION: Co-sleeping may
increase the risk of NE in primary school children, particularly in those aged 11
to 12 years.
PMID- 24351700
TI - Predictors of improvement in cardiometabolic risk factors with weight loss in
women.
AB - BACKGROUND: Weight loss is associated with improvements in cardiometabolic risk
factors, including serum glucose, insulin, C-reactive protein, and blood lipids.
Few studies have evaluated the long-term (>18 months) effect of weight loss on
these risk factors or sought to identify factors associated with sustained
improvements in these measures. METHODS AND RESULTS: In 417 overweight/obese
women (mean [SD] age, 44 [10] years) participating in a weight loss trial, we
sought to identify predictors of weight loss-associated cardiometabolic risk
factors after 12 and 24 months of intervention. Total cholesterol (TC), low
density lipoprotein (LDL)-cholesterol (LDL-C), high-density lipoprotein (HDL)
cholesterol, non-HDL-cholesterol, triglycerides (TG), insulin, glucose, C
reactive protein (CRP), and cardiopulmonary fitness were measured at baseline and
at 12 and 24 months. After 24 months, significant reductions in body weight,
waist circumference, CRP, TC, HDL-cholesterol, and non-HDL-cholesterol were
observed (P<0.01). After 24 months, mean TC and non-HDL-cholesterol were reduced
regardless of the amount of weight lost, whereas reductions in LDL-cholesterol,
CRP, insulin, and TG were observed only in those who lost >=10% body weight. Step
test performance improved only in those who lost >=10% body weight after 24
months. Change in weight demonstrated a positive predictive value for change in
cholesterol, insulin, glucose, and triglycerides. Baseline level of the biomarker
showed the greatest predictive value for follow-up measures for insulin,
cholesterol, glucose, and triglycerides. CONCLUSIONS: Our data extend the results
from short-term weight loss trials and suggest that the magnitude of weight loss
and baseline values for risk factors are associated with improvements in
cardiometabolic risk factors even after 24 months. CLINICAL TRIALS REGISTRATION
INFORMATION URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00640900.
PMID- 24351701
TI - Cardiovascular disease and cognitive decline in postmenopausal women: results
from the Women's Health Initiative Memory Study.
AB - BACKGROUND: Data on cardiovascular diseases (CVD) and cognitive decline are
conflicting. Our objective was to investigate if CVD is associated with an
increased risk for cognitive decline and to examine whether hypertension,
diabetes, or adiposity modify the effect of CVD on cognitive functioning. METHODS
AND RESULTS: Prospective follow-up of 6455 cognitively intact, postmenopausal
women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory
Study (WHIMS). CVD was determined by self-report. For cognitive decline, we
assessed the incidence of mild cognitive impairment (MCI) or probable dementia
(PD) via modified mini-mental state examination (3 MS) score, neurocognitive, and
neuropsychiatric examinations. The median follow-up was 8.4 years. Women with CVD
tended to be at increased risk for cognitive decline compared with those free of
CVD (hazard ratio [HR], 1.29; 95% CI: 1.00, 1.67). Women with myocardial
infarction or other vascular disease were at highest risk (HR, 2.10; 95% CI:
1.40, 3.15 or HR, 1.97; 95% CI: 1.34, 2.87). Angina pectoris was moderately
associated with cognitive decline (HR 1.45; 95% CI: 1.05, 2.01) whereas no
significant relationships were found for atrial fibrillation or heart failure.
Hypertension and diabetes increased the risk for cognitive decline in women
without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No
significant trend was seen for adiposity. CONCLUSIONS: CVD is associated with
cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but
not adiposity, are associated with a higher risk for cognitive decline. More
research is warranted on the potential of CVD prevention for preserving cognitive
functioning.
PMID- 24351703
TI - Connecting cardiovascular disease and dementia: further evidence.
PMID- 24351702
TI - Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and
incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.
AB - BACKGROUND: Dietary guidelines support intake of polyunsaturated fatty acids
(PUFAs) in fish and vegetable oils. However, some controversy remains about
benefits of PUFAs, and most prior studies have relied on self-reported dietary
assessment in relatively homogeneous populations. METHODS AND RESULTS: In a
multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans,
Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000
2002) using gas chromatography and dietary PUFAs estimated using a food frequency
questionnaire. Incident cardiovascular disease (CVD) events (including coronary
heart disease and stroke; n=189) were prospectively identified through 2010
during 19 778 person-years of follow-up. In multivariable-adjusted Cox models,
circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely
associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of
0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for
docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n-3 Docosapentaenoic acid
(DPA) was inversely associated with CVD in whites and Chinese, but not in other
race/ethnicities (P-interaction=0.01). No significant associations with CVD were
observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid,
arachidonic acid). Associations with CVD of self-reported dietary PUFA were
consistent with those of the PUFA biomarkers. All associations were similar
across racial-ethnic groups, except those of docosapentaenoic acid. CONCLUSIONS:
Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but
not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD
incidence. These findings suggest that increased consumption of n-3 PUFA from
seafood may prevent CVD development in a multiethnic population.
PMID- 24351704
TI - The influence of the length of the first metatarsal on the risk of reulceration
in the feet of patients with diabetes.
AB - Our aim was to identify the optimal diagnostic cutoff point on the scale of
protrusion measurements of the first metatarsal (M1) to predict the probability
of reulceration after metatarsal head resection in patients with diabetes
mellitus. We conducted a prospective study of patients with diabetes who
underwent resection of at least 1 metatarsal head in our department. After
surgery, we measured the difference in length (protrusion) between the M1 and the
longest of the 4 lesser metatarsals by radiographic view. The patients were
divided into those in whom the M1 was the longest of the 5 metatarsals (group 1)
and patients in whom at least one of the lesser metatarsals was longer than the
M1 (group 2). They were followed-up for 12 months and were assessed for
reulceration. Ninety-one patients were included in the present study: 43 (47%) in
group 1 and 48 (53%) in group 2. In group 1, the longer the protrusion of M1 was,
the higher the probability for reulceration (P < .001, 95% confidence interval =
0.813-0.997). In group 2, the shorter the protrusion of M1, the higher the
probability for reulceration (P = .002, 95% confidence interval = 0.628-0.905).
The optimal cutoff point for group 1 was 11 mm (sensitivity = 84.6%, specificity
= 86.7%) for the probability of reulceration. In group 2, it was -7 mm
(sensitivity = 81.8%, specificity = 65.4%). These results suggest that M1
protrusion is an optimum prognostic indicator for reulceration and could be
recommended for detecting patients at risk of reulceration after surgery.
PMID- 24351705
TI - Wound healing activity of the inflorescence of Typha elephantina (Cattail).
AB - Methanolic extracts of Typha elephantina inflorescence (TE) and its bandage were
screened for wound healing by incision and excision wound models in Wistar rats.
In the incision wound model, incision wounds were topically treated with TE gel
(2.0% [w/w], 3.0% [w/w], and 5.0% [w/w]), Typha elephantina inflorescence
bandage, and the reference standard 5.0% w/w povidone iodine for a period of 10
days. When the wounds healed thoroughly, sutures were removed on the 8th
postwounding day, and the tensile strength of the skin was measured on the 10th
day. In the excision wound model, excision wounds were treated with TE gel (3.0%
[w/w] and 5.0% [w/w]), inflorescence bandage, and 5.0% w/w povidone iodine till
the wounds completely healed. Epithelization time, wound contraction,
hydroxyproline and hexosamine content of the scab, and ascorbic acid and
malondialdehyde content of the plasma were determined in this model. In the
incision wound model, high tensile strength of the skin of the healed wound was
observed in rats treated with the TE gels and the inflorescence bandage when
compared with wounded control rats. The increase in tensile strength indicates a
promotion of collagen fibers and a firm knitting of the disrupted wound surfaces
by collagen. In the excision wound model, higher rate of wound contraction,
decreased period of epithelization, elevated hydroxyproline, hexosamine, and
ascorbic acid levels, and a significant decrease in malondialdehyde content was
observed in treated groups when compared with the wounded control animals. It may
be concluded that the inflorescence of Typha elephantina possesses a potent wound
healing activity, which may be due to an underlying antioxidant mechanism.
PMID- 24351706
TI - Investigation of the structure of alpha-lactalbumin protein nanotubes using
optical spectroscopy.
AB - Alpha-lactalbumin (alpha-la) is one of the major proteins in whey. When partially
hydrolysed with Bacillus licheniformis protease, it produces nanotubular
structures in the presence of calcium ions by a self-assembly process. This study
presents investigation of alpha-la protein structure during hydrolysis and
nanotube formation using optical spectroscopy. Before spectroscopic measurements,
nanotubes were examined with microscopy. The observed alpha-la nanotubes (alpha
LaNTs) were in the form of regular hollow strands with a diameter of about 20 nm
and the average length of 1 MUm. Amide and backbone vibration bands of the Raman
spectra displayed remarkable conformational changes in alpha and beta domains in
the protein structure during nanotube growth. This was confirmed by the Fourier
transform infrared (FTIR) spectroscopy data. Also, FTIR analysis revealed certain
bands at calcium (Ca++) binding sites of COO- groups in hydrolysed protein. These
sites might be critical in nanotube elongation.
PMID- 24351707
TI - Hospital admissions caused by adverse drug events: an Australian prospective
study.
AB - OBJECTIVE: To assess the frequency of adverse drug event (ADE)-related admissions
(ADE-RAs) during a prospective medical record review of patients admitted to a
metropolitan tertiary referral hospital. METHODS: Potential ADE-RA cases were
identified by examination of case records of randomly selected patients. Cases
were assessed by an expert panel to measure study outcomes, which were the
frequency (ADEs and ADE-RAs) as well as type, likelihood of causality, severity,
avoidability and detection of ADEs. RESULTS: Of the 370 subjects, 59 (16.0%) had
a confirmed ADE-RA, with 15 (4.1%) of these serious and preventable. The 59 ADE
RAs were a result of 72 discreet ADEs. Adverse drug reactions were the most
common type of ADE, followed by non-compliance. Of the 72 discreet ADEs, 31.9%
were classified as 'probable' or 'highly probable'. Most ADEs (54.2%) were
classified as 'definitely avoidable', 34.7% were classified as 'severe' and 21.8%
were classified as both 'definitely avoidable' and 'severe'. Half the ADEs were
detected after the patient had been admitted and most were detected by medical
practitioners. Antineoplastics followed by antidiabetic agents were most
frequently implicated. CONCLUSIONS: Implementing a systems approach that involves
multiple strategies, such as improving tertiary-to-primary care information
transfer and promoting medication adherence through education programs, is
necessary to tackle the problem of avoidable ADE-RAs and the associated cost
burden. WHAT IS KNOWN ABOUT THE TOPIC? It is estimated that 2-3% of Australian
hospital admissions are due to adverse drug events (ADEs), but recent data are
lacking. According to the Australian Statistics on Medicines, over 250 million
prescriptions were dispensed in 2007, compared with just under 180 million in
1997. This 40% increase in drug utilisation over the 10 years surpasses the
Australian population growth of 14% in the same period. An increase in drug use
per person indicates that the rate of ADEs and possible ADE-related admissions
(ADE-RAs) is likely to have increased. WHAT DOES THIS PAPER ADD? This prospective
study was conducted at a large Australian metropolitan teaching hospital and we
report that 59 of 370 participants (16.0%) presenting to the Emergency Department
had a confirmed ADE-RA, with 15 (4.1%) presenting with a serious and preventable
ADE-RA. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The findings of this study
support implementing a systems approach involving multiple strategies to tackle
the problem of avoidable ADE-RAs and the associated cost burden. This study
reveals that half the ADEs were not detected until after the admission process,
which reinforces the importance of focusing efforts towards preventing ADE-RAs
and detecting ADE-RAs through measures such as those recommended in the
Australian Pharmaceutical Advisory Council guiding principles.
PMID- 24351708
TI - Wigwams: identifying gene modules co-regulated across multiple biological
conditions.
AB - MOTIVATION: Identification of modules of co-regulated genes is a crucial first
step towards dissecting the regulatory circuitry underlying biological processes.
Co-regulated genes are likely to reveal themselves by showing tight co
expression, e.g. high correlation of expression profiles across multiple time
series datasets. However, numbers of up- or downregulated genes are often large,
making it difficult to discriminate between dependent co-expression resulting
from co-regulation and independent co-expression. Furthermore, modules of co
regulated genes may only show tight co-expression across a subset of the time
series, i.e. show condition-dependent regulation. RESULTS: Wigwams is a simple
and efficient method to identify gene modules showing evidence for co-regulation
in multiple time series of gene expression data. Wigwams analyzes similarities of
gene expression patterns within each time series (condition) and directly tests
the dependence or independence of these across different conditions. The
expression pattern of each gene in each subset of conditions is tested
statistically as a potential signature of a condition-dependent regulatory
mechanism regulating multiple genes. Wigwams does not require particular time
points and can process datasets that are on different time scales. Differential
expression relative to control conditions can be taken into account. The output
is succinct and non-redundant, enabling gene network reconstruction to be focused
on those gene modules and combinations of conditions that show evidence for
shared regulatory mechanisms. Wigwams was run using six Arabidopsis time series
expression datasets, producing a set of biologically significant modules spanning
different combinations of conditions. AVAILABILITY AND IMPLEMENTATION: A Matlab
implementation of Wigwams, complete with graphical user interfaces and
documentation, is available at: warwick.ac.uk/wigwams. .
PMID- 24351709
TI - CrossMap: a versatile tool for coordinate conversion between genome assemblies.
AB - MOTIVATION: Reference genome assemblies are subject to change and refinement from
time to time. Generally, researchers need to convert the results that have been
analyzed according to old assemblies to newer versions, or vice versa, to
facilitate meta-analysis, direct comparison, data integration and visualization.
Several useful conversion tools can convert genome interval files in browser
extensible data or general feature format, but none have the functionality to
convert files in sequence alignment map or BigWig format. This is a significant
gap in computational genomics tools, as these formats are the ones most widely
used for representing high-throughput sequencing data, such as RNA-seq, chromatin
immunoprecipitation sequencing, DNA-seq, etc. RESULTS: Here we developed
CrossMap, a versatile and efficient tool for converting genome coordinates
between assemblies. CrossMap supports most of the commonly used file formats,
including BAM, sequence alignment map, Wiggle, BigWig, browser extensible data,
general feature format, gene transfer format and variant call format.
AVAILABILITY AND IMPLEMENTATION: CrossMap is written in Python and C. Source code
and a comprehensive user's manual are freely available at:
http://crossmap.sourceforge.net/.
PMID- 24351710
TI - Site-heterogeneous mutation-selection models within the PhyloBayes-MPI package.
AB - MOTIVATION: In recent years, there has been an increasing interest in the
potential of codon substitution models for a variety of applications. However,
the computational demands of these models have sometimes lead to the adoption of
oversimplified assumptions, questionable statistical methods or a limited focus
on small data sets. RESULTS: Here, we offer a scalable, message-passing-interface
based Bayesian implementation of site-heterogeneous codon models in the mutation
selection framework. Our software jointly infers the global mutational parameters
at the nucleotide level, the branch lengths of the tree and a Dirichlet process
governing across-site variation at the amino acid level. We focus on an example
estimation of the distribution of selection coefficients from an alignment of
several hundred sequences of the influenza PB2 gene, and highlight the site
specific characterization enabled by such a modeling approach. Finally, we
discuss future potential applications of the software for conducting evolutionary
inferences. AVAILABILITY AND IMPLEMENTATION: The models are implemented within
the PhyloBayes-MPI package, (available at phylobayes.org) along with usage
details in the accompanying manual.
PMID- 24351711
TI - Appearance of Planktothrix rubescens bloom with [D-Asp3, Mdha7]MC-RR in gravel
pit pond of a shallow lake-dominated area.
AB - Blooms of toxic cyanobacteria are well-known phenomena in many regions of the
world. Microcystin (MC), the most frequent cyanobacterial toxin, is produced by
entirely different cyanobacteria, including unicellular, multicellular
filamentous, heterocytic, and non-heterocytic bloom-forming species. Planktothrix
is one of the most important MC-producing genera in temperate lakes. The reddish
color of cyanobacterial blooms viewed in a gravel pit pond with the appearance of
a dense 3 cm thick layer (biovolume: 28.4 mm(3) L(-1)) was an unexpected
observation in the shallow lake-dominated alluvial region of the Carpathian
Basin. [D-Asp(3), Mdha(7)]MC-RR was identified from the blooms sample by MALDI
TOF and NMR. Concentrations of [D-Asp(3), Mdha(7)]MC-RR were measured by
capillary electrophoresis to compare the microcystin content of the field samples
and the isolated, laboratory-maintained P. rubescens strain. In analyzing the MC
gene cluster of the isolated P. rubescens strain, a deletion in the spacer region
between mcyE and mcyG and an insertion were located in the spacer region between
mcyT and mcyD. The insertion elements were sequenced and partly identified.
Although some invasive tropical cyanobacterial species have been given a great
deal of attention in many recent studies, our results draw attention to the
spread of the alpine organism P. rubescens as a MC-producing, bloom-forming
species.
PMID- 24351712
TI - Evolution stings: the origin and diversification of scorpion toxin peptide
scaffolds.
AB - The episodic nature of natural selection and the accumulation of extreme sequence
divergence in venom-encoding genes over long periods of evolutionary time can
obscure the signature of positive Darwinian selection. Recognition of the true
biocomplexity is further hampered by the limited taxon selection, with easy to
obtain or medically important species typically being the subject of intense
venom research, relative to the actual taxonomical diversity in nature. This
holds true for scorpions, which are one of the most ancient terrestrial venomous
animal lineages. The family Buthidae that includes all the medically significant
species has been intensely investigated around the globe, while almost completely
ignoring the remaining non-buthid families. Australian scorpion lineages, for
instance, have been completely neglected, with only a single scorpion species
(Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack
of venom composition and toxin sequence information from an entire continent's
worth of scorpions has impeded our understanding of the molecular evolution of
scorpion venom. The molecular origin, phylogenetic relationships and evolutionary
histories of most scorpion toxin scaffolds remain enigmatic. In this study, we
have sequenced venom gland transcriptomes of a wide taxonomical diversity of
scorpions from Australia, including buthid and non-buthid representatives. Using
state-of-art molecular evolutionary analyses, we show that a majority of
CSalpha/beta toxin scaffolds have experienced episodic influence of positive
selection, while most non-CSalpha/beta linear toxins evolve under the extreme
influence of negative selection. For the first time, we have unraveled the
molecular origin of the major scorpion toxin scaffolds, such as scorpion venom
single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot
(ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides
(BPP), linear non-disulphide bridged peptides and antimicrobial peptides (AMP).
We have thus demonstrated that even neglected lineages of scorpions are a rich
pool of novel biochemical components, which have evolved over millions of years
to target specific ion channels in prey animals, and as a result, possess
tremendous implications in therapeutics.
PMID- 24351713
TI - A proteomics and transcriptomics investigation of the venom from the barychelid
spider Trittame loki (brush-foot trapdoor).
AB - Although known for their potent venom and ability to prey upon both invertebrate
and vertebrate species, the Barychelidae spider family has been entirely
neglected by toxinologists. In striking contrast, the sister family Theraphosidae
(commonly known as tarantulas), which last shared a most recent common ancestor
with Barychelidae over 200 million years ago, has received much attention,
accounting for 25% of all the described spider toxins while representing only 2%
of all spider species. In this study, we evaluated for the first time the venom
arsenal of a barychelid spider, Trittame loki, using transcriptomic, proteomic,
and bioinformatic methods. The venom was revealed to be dominated by extremely
diverse inhibitor cystine knot (ICK)/knottin peptides, accounting for 42 of the
46 full-length toxin precursors recovered in the transcriptomic sequencing. In
addition to documenting differential rates of evolution adopted by different
ICK/knottin toxin lineages, we discovered homologues with completely novel
cysteine skeletal architecture. Moreover, acetylcholinesterase and neprilysin
were revealed for the first time as part of the spider-venom arsenal and CAP
(CRiSP/Allergen/PR-1) were identified for the first time in mygalomorph spider
venoms. These results not only highlight the extent of venom diversification in
this neglected ancient spider lineage, but also reinforce the idea that unique
venomous lineages are rich pools of novel biomolecules that may have significant
applied uses as therapeutics and/or insecticides.
PMID- 24351714
TI - Phormidium autumnale growth and anatoxin-a production under iron and copper
stress.
AB - Studies on planktonic cyanobacteria have shown variability in cyanotoxin
production, in response to changes in growth phase and environmental factors. Few
studies have investigated cyanotoxin regulation in benthic mat-forming species,
despite increasing reports on poisoning events caused by ingestion of these
organisms. In this study, a method was developed to investigate changes in
cyanotoxin quota in liquid cultures of benthic mat-forming cyanobacteria. Iron
and copper are important in cellular processes and are well known to affect
growth and selected metabolite production in cyanobacteria and algae. The effect
of iron (40-4000 MUg L(-1)) and copper (2.5-250 MUg L(-1)) on growth and anatoxin
a quota in Phormidium autumnale was investigated in batch culture. These
concentrations were chosen to span those found in freshwater, as well as those
previously reported to be toxic to cyanobacteria. Anatoxin-a concentrations
varied throughout the growth curve, with a maximum quota of between 0.49 and 0.55
pg cell(-1) measured within the first two weeks of growth. Growth rates were
significantly affected by copper and iron concentrations (P < 0.0001); however,
no statistically significant difference between anatoxin-a quota maxima was
observed. When the iron concentrations were 800 and 4000 MUg L(-1), the P.
autumnale cultures did not firmly attach to the substratum. At 250 MUg L(-1)
copper or either 40 or 4000 MUg L(-1) iron, growth was suppressed.
PMID- 24351715
TI - Analysis of deoxynivalenol and deoxynivalenol-3-glucoside in hard red spring
wheat inoculated with Fusarium graminearum.
AB - Deoxynivalenol (DON) is a mycotoxin affecting wheat quality. The formation of the
"masked" mycotoxin deoxinyvalenol-3-glucoside (D3G) results from a defense
mechanism the plant uses for detoxification. Both mycotoxins are important from a
food safety point of view. The aim of this work was to analyze DON and D3G
content in inoculated near-isogenic wheat lines grown at two locations in
Minnesota, USA during three different years. Regression analysis showed positive
correlation between DON content measured with LC and GC among wheat lines,
locality and year. The relationship between DON and D3G showed a linear increase
until a certain point, after which the DON content and the D3G increased. Wheat
lines having higher susceptibility to Fusarium showed the opposite trend. ANOVA
demonstrated that the line and location have a greater effect on variation of DON
and D3G than do their interaction among years. The most important factor
affecting DON and D3G was the growing location. In conclusion, the year,
environmental conditions and location have an effect on the D3G/DON ratio in
response to Fusarium infection.
PMID- 24351716
TI - Secreted phospholipases A2 of snake venoms: effects on the peripheral
neuromuscular system with comments on the role of phospholipases A2 in disorders
of the CNS and their uses in industry.
AB - Neuro- and myotoxicological signs and symptoms are significant clinical features
of envenoming snakebites in many parts of the world. The toxins primarily
responsible for the neuro and myotoxicity fall into one of two categories--those
that bind to and block the post-synaptic acetylcholine receptors (AChR) at the
neuromuscular junction and neurotoxic phospholipases A2 (PLAs) that bind to and
hydrolyse membrane phospholipids of the motor nerve terminal (and, in most cases,
the plasma membrane of skeletal muscle) to cause degeneration of the nerve
terminal and skeletal muscle. This review provides an introduction to the
biochemical properties of secreted sPLA2s in the venoms of many dangerous snakes
and a detailed discussion of their role in the initiation of the neurologically
important consequences of snakebite. The rationale behind the experimental
studies on the pharmacology and toxicology of the venoms and isolated PLAs in the
venoms is discussed, with particular reference to the way these studies allow one
to understand the biological basis of the clinical syndrome. The review also
introduces the involvement of PLAs in inflammatory and degenerative disorders of
the central nervous system (CNS) and their commercial use in the food industry.
It concludes with an introduction to the problems associated with the use of
antivenoms in the treatment of neuro-myotoxic snakebite and the search for
alternative treatments.
PMID- 24351717
TI - Expression of VEGF and Flk-1 and Flt-1 receptors during blood-brain barrier (BBB)
impairment following Phoneutria nigriventer spider venom exposure.
AB - Apart from its angiogenic and vascular permeation activity, the vascular
endothelial growth factor (VEGF) has been also reported as a potent neuronal
protector. Newborn rats with low VEGF levels develop neuron degeneration, while
high levels induce protective mechanisms in several neuropathological conditions.
Phoneutria nigriventer spider venom (PNV) disrupts the blood-brain barrier (BBB)
and causes neuroinflammation in central neurons along with excitotoxic signals in
rats and humans. All these changes are transient. Herein, we examined the
expression of VEGF and its receptors, Flt-1 and Flk-1 in the hippocampal neurons
following envenomation by PNV. Adult and neonatal rats were evaluated at time
limits of 2, 5 and 24 h. Additionally, BBB integrity was assessed by measuring
the expression of occludin, beta-catenin and laminin and neuron viability was
evaluated by NeuN expression. VEGF, Flt-1 and Flk-1 levels increased in PNV
administered rats, concurrently with respective mRNAs. Flt-1 and Flk-1
immunolabeling was nuclear in neurons of hippocampal regions, instead of the VEGF
membrane-bound typical location. These changes occurred simultaneously with the
transient decreases in BBB-associated proteins and NeuN positivity. Adult rats
showed more prominent expressional increases of the VEGF/Flt-1/Flk-1 system and
earlier recovery of BBB-related proteins than neonates. We conclude that the
reactive expressional changes seen here suggest that VEGF and receptors could
have a role in the excitotoxic mechanism of PNV and that such role would be less
efficient in neonate rats.
PMID- 24351720
TI - Occurrence of deoxynivalenol and deoxynivalenol-3-glucoside in hard red spring
wheat grown in the USA.
AB - Deoxynivalenol (DON) is a mycotoxin found in wheat that is infected with Fusarium
fungus. DON may also be converted to a type of "masked mycotoxin", named
deoxynivalenol-3-glucoside (D3G), as a result of detoxification of the plant. In
this study, DON and D3G were measured using gas chromatographic (GC) and liquid
chromatography-mass spectrometry (LC-MS) in wheat samples collected during 2011
and 2012 in the USA. Results indicate that the growing region had a significant
effect on the DON and D3G (p < 0.0001). There was a positive correlation between
both methods (GC and LC-MS) used for determination of DON content. DON showed a
significant and positive correlation with D3G during 2011. Overall, DON
production had an effect on D3G content and kernel damage, and was dependent on
environmental conditions during Fusarium infection.
PMID- 24351718
TI - Towards clinical applications of anti-endotoxin antibodies; a re-appraisal of the
disconnect.
AB - Endotoxin is a potent mediator of a broad range of patho-physiological effects in
humans. It is present in all Gram negative (GN) bacteria. It would be expected
that anti-endotoxin therapies, whether antibody based or not, would have an
important adjuvant therapeutic role along with antibiotics and other supportive
therapies for GN infections. Indeed there is an extensive literature relating to
both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the
extent of disconnect between the generally successful pre-clinical studies versus
the failures of the numerous large clinical trials of antibody based and other
anti-endotoxin therapies is under-appreciated and unexplained. Seeking a
reconciliation of this disconnect is not an abstract academic question as
clinical trials of interventions to reduce levels of endotoxemia levels are
ongoing. The aim of this review is to examine new insights into the complex
relationship between endotoxemia and sepsis in an attempt to bridge this
disconnect. Several new factors to consider in this reappraisal include the
frequency and types of GN bacteremia and the underlying mortality risk in the
various study populations. For a range of reasons, endotoxemia can no longer be
considered as a single entity. There are old clinical trials which warrant a re
appraisal in light of these recent advances in the understanding of the structure
function relationship of endotoxin. Fundamentally however, the disconnect not
only remains, it has enlarged.
PMID- 24351719
TI - Venom down under: dynamic evolution of Australian elapid snake toxins.
AB - Despite the unparalleled diversity of venomous snakes in Australia, research has
concentrated on a handful of medically significant species and even of these very
few toxins have been fully sequenced. In this study, venom gland transcriptomes
were sequenced from eleven species of small Australian elapid snakes, from eleven
genera, spanning a broad phylogenetic range. The particularly large number of
sequences obtained for three-finger toxin (3FTx) peptides allowed for robust
reconstructions of their dynamic molecular evolutionary histories. We
demonstrated that each species preferentially favoured different types of alpha
neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three
forms of alpha-neurotoxin [Type I (also known as (aka): short-chain), Type II
(aka: long-chain) and Type III] not only adopted differential rates of evolution,
but have also conserved a diversity of residues, presumably to potentiate prey
specific toxicity. Despite these differences, the different alpha-neurotoxin
types were shown to accumulate mutations in similar regions of the protein,
largely in the loops and structurally unimportant regions, highlighting the
significant role of focal mutagenesis. We theorize that this phenomenon not only
affects toxin potency or specificity, but also generates necessary variation for
preventing/delaying prey animals from acquiring venom-resistance. This study also
recovered the first full-length sequences for multimeric phospholipase A2 (PLA2)
'taipoxin/paradoxin' subunits from non-Oxyuranus species, confirming the early
recruitment of this extremely potent neurotoxin complex to the venom arsenal of
Australian elapid snakes. We also recovered the first natriuretic peptides from
an elapid that lack the derived C-terminal tail and resemble the plesiotypic form
(ancestral character state) found in viper venoms. This provides supporting
evidence for a single early recruitment of natriuretic peptides into snake
venoms. Novel forms of kunitz and waprin peptides were recovered, including dual
domain kunitz-kunitz precursors and the first kunitz-waprin hybrid precursors
from elapid snakes. The novel sequences recovered in this study reveal that the
huge diversity of unstudied venomous Australian snakes are of considerable
interest not only for the investigation of venom and whole organism evolution but
also represent an untapped bioresource in the search for novel compounds for use
in drug design and development.
PMID- 24351721
TI - In vitro glucuronidation of ochratoxin a by rat liver microsomes.
AB - Ochratoxin A (OTA), one of the most toxic mycotoxins, can contaminate a wide
range of food and feedstuff. To date, the data on its conjugates via
glucuronidation request clarification and consolidation. In the present study,
the combined approaches of ultra high performance liquid chromatography-tandem
mass spectrometry (UHPLC-MS/MS), UHPLC-Orbitrap-high resolution mass spectrometry
(HRMS) and liquid chromatography-multiple stage mass spectrometry (LC-MS(n)) were
utilized to investigate the metabolic profile of OTA in rat liver microsomes.
Three conjugated products of OTA corresponding to amino-, phenol- and acyl
glucuronides were identified, and the related structures were confirmed by
hydrolysis with beta-glucuronidase. Moreover, OTA methyl ester, OTalpha and
OTalpha-glucuronide were also found in the reaction solution. Based on these
results, an in vitro metabolic pathway of OTA has been proposed for the first
time.
PMID- 24351722
TI - Effects of tissue mechanical properties on susceptibility to histotripsy-induced
tissue damage.
AB - Histotripsy is a non-invasive tissue ablation method capable of fractionating
tissue by controlling acoustic cavitation. To determine the fractionation
susceptibility of various tissues, we investigated histotripsy-induced damage on
tissue phantoms and ex vivo tissues with different mechanical strengths. A
histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long
ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and
1000 Hz. Results showed significantly smaller lesions were generated in tissue
phantoms of higher mechanical strength. Histotripsy was also applied to 43
different ex vivo porcine tissues with a wide range of mechanical properties.
Gross morphology demonstrated stronger tissues with higher ultimate stress,
higher density, and lower water content were more resistant to histotripsy damage
in comparison to weaker tissues. Based on these results, a self-limiting vessel
sparing treatment strategy was developed in an attempt to preserve major vessels
while fractionating the surrounding target tissue. This strategy was tested in
porcine liver in vivo. After treatment, major hepatic blood vessels and bile
ducts remained intact within a completely fractionated liver volume. These
results identify varying susceptibilities of tissues to histotripsy therapy and
provide a rational basis to optimize histotripsy parameters for treatment of
specific tissues.
PMID- 24351724
TI - Tipping the obesity problem: Silliness, silos, and sense.
PMID- 24351723
TI - Slicing tRNAs to boost functional ncRNA diversity.
AB - Post-transcriptional cleavage of RNA molecules to generate smaller fragments is a
widespread mechanism that enlarges the structural and functional complexity of
cellular RNomes. Substrates for such RNA fragmentations are coding as well as non
protein-coding RNAs. In particular, fragments derived from both precursor and
mature tRNAs represent one of the rapidly growing classes of post-transcriptional
RNA pieces. Importantly, these tRNA fragments possess distinct expression
patterns, abundance, cellular localizations, or biological roles compared with
their parental tRNA molecules. Here we review recent reports on tRNA cleavage and
attempt to categorize tRNA pieces according to their origin and cellular
function. The biological scope of tRNA-derived fragments ranges from translation
control, over RNA silencing, to regulating apoptosis, and thus clearly enlarges
the functional repertoire of ncRNA biology.
PMID- 24351725
TI - Baby boomers, obesity, and social change.
AB - SUMMARY: Baby boomers are currently in mid-life and over the next several decades
they will swell the ranks of those aged 65 and over. Their entry into this age
group will have a significant impact in a number of areas but particularly in
relation to the type and extent of health services required. Obesity is a major
health issue for this cohort as its members are significantly over-represented in
both the overweight and obese categories compared to the rest of the population.
In addition, they are significantly more likely to have multiple risk factors.
This review considers how alterations to lifestyle, initiated by the rapid social
changes of the last half century, might have contributed to obesity within this
cohort. In providing this broad overview it focuses on how increased affluence
and changes to everyday institutions have affected the cultures around food
consumption. This includes a consideration of both the internal and external ways
in which eating environments are now constructed. This review suggests that
further research is needed to identify the factors which facilitate or constrain
healthy ageing in the baby boom cohort. Research along these lines also needs to
consider both macro- and micro-level changes to the social context within which
these factors arise. This is essential as the high levels of obesity in this
cohort may reflect both an individual and a structural lag in adapting lifestyles
and policies to meet the needs of this very different social environment.:
PMID- 24351726
TI - Obesity and time-inconsistent preferences.
AB - SUMMARY: As obesity becomes a major health and economic issue of the current age,
interventions and policies are being targeted to influence individuals' diet and
exercise behaviors. Examining the deviations of reality from a baseline model of
rational choice provides insights into the economic rationales for interventions
to modify individuals' choices. In addition to the more classical economic
rationales for intervention, insights from behavioral economics and psychology
have recently led to a focus on the role of time-inconsistent preferences, in
particular present-biased preferences, in the choices that lead to obesity. While
individuals can use self-control techniques to mitigate the problem, there is
also potential for targeted interventions and policies to improve the welfare of
individuals. Further interdisciplinary research in the area may lead to
behavioral obesity interventions tailored to individuals' incentives, resulting
in higher compliance rates.:
PMID- 24351727
TI - Asthma is associated with cardiovascular disease in a representative population
sample.
AB - SUMMARY: RATIONALE: People with asthma may have an increased risk of
cardiovascular disease (CVD) and metabolic disorders due to the direct
involvement of common inflammatory mediators in the pathogenesis of CVD and
insulin resistance. The aim of this study was to determine whether asthma was
associated with an increased prevalence of CVD/stroke, and diabetes in a cross
sectional population study and whether the relationship was modified by obesity.
METHODS: The North West Adelaide Health Study (NWAHS) (n = 4060, age >=18 years)
clinical assessment included spirometry, anthropometry, blood pressure, fasting
lipids, glucose and HbA1c. Questionnaires assessed doctor diagnosed asthma,
diabetes, CVD (myocardial infarction, angina)/stroke, smoking status, and
demographics. Asthma was identified by self-report or significant bronchodilator
reversibility of lung function. RESULTS: After adjustment for known risk factors
and confounders, asthma was not associated with diabetes (odds ratio (OR) = 1.06,
95% confidence interval (CI): 0.45-2.49, p = .91) yet remained positively
associated with CVD/stroke (OR = 1.82, 95% CI: 1.20-2.73, p < 0.01) independent
of the level of BMI (p for interaction between asthma and BMI = .22), smoking and
lung function. Asthma was not positively associated with CVD risk factors or the
metabolic syndrome. CONCLUSIONS: In a representative population sample, asthma
was associated with CVD/stroke after adjustment for traditional risk factors and
lung function. Asthma may lead to CVD events via pathways unrelated to
traditional risk factors and this requires further investigation. No significant
effect modification by BMI was observed in relation to CVD, or diabetes.
PMID- 24351728
TI - Perceived hunger, palatability, and adherence: A comparison of high- and low-fat
diets.
AB - SUMMARY: OBJECTIVE: To investigate whether there is a difference in palatability
and perceived hunger between high- and low-fat diets, and furthermore to see if
any such differences are correlated with the degree of adherence to a diet and
with weight reduction. DESIGN: Randomised, parallel, two-arm, open-label 10-week
dietary intervention study comparing two hypocaloric (-600 kcal/day) diets with a
fat energy percent of 20-25 or 40-45. SUBJECTS: Obese (BMI >=30 kg/m(2)) but
otherwise healthy adult subjects (n = 100). MEASUREMENTS: Perceived hunger,
palatability of diet, difficulty of following dietary instructions and adherence
to diet by visual analogue scales, and body weight loss. RESULTS: There were no
significant differences between the low- and high-fat groups in perceived hunger,
palatability, difficulty of following instructions, nor adherence to the diet.
There were significant trends towards lower perceived hunger during the trial
[F(1, 86) = 49.99, p < .001], towards increased perceived adherence [z = 2.851, p
= .004], and towards less perceived difficulty of following both diets during the
second and third week [F(1, 86) = 23.51, p < .001]. Median weight loss was 7%.
The patients who reached at least median weight loss decreased their perceived
hunger significantly more than the group who did not [F(1, 85) = 4.12, p = .046],
and had less difficulty of following instructions throughout the treatment period
[F(1, 85) = 4.35, p = .040]. There was a strong negative correlation between
perceived hunger and palatability [-.55] as well as between difficulty of
following instructions and palatability [-.45], and a strong positive correlation
between difficulty of following instructions and perceived hunger [.63] with both
diets. CONCLUSIONS: The perceived hunger during the diet intervention and
palatability of the diet are important factors for succeeding with weight
reduction. The fat proportion of the diets was not important for determining
perceived hunger and palatability. These findings suggest that the ability to
compose a palatable and satiating diet may be important for successful weight
reduction.
PMID- 24351729
TI - Obesity and the effects of choice at a fast food restaurant.
AB - SUMMARY: Fast food is often mentioned when investigating the obesity epidemic.
While many health professionals generally perceive of fast foods as 'bad', a new
perspective of manageable fast food consumption has been suggested. The
macronutrient content of traditional fast food meals and healthier choices from
six of the dominant fast food chains in Australia were calculated to determine
the nutritional outcomes of a fast food meal. On average, a traditional fast food
meal accounted for 47.47% of an 8400 kJ daily guideline. Total fat, however,
accounted for between 47.08% and 93.48% of a daily guideline. The healthier
choices were lower in overall kilojoule (kJ) and total fat. Fast food is
increasingly becoming part of our eating patterns. Traditional fast food meals
are indeed energy dense. In terms of kilojoule intake alone, a traditional fast
food meal can be incorporated reasonably into a daily intake without necessarily
promoting obesity. Health professionals should educate consumers of the simple
'healthy' choices they can make when eating fast food.:
PMID- 24351730
TI - Weight reduction improves nocturnal respiration in obese sleep apnoea patients-A
randomized controlled pilot study.
AB - SUMMARY: OBJECTIVES: Randomized controlled pilot study of the effect of weight
reduction on nocturnal respiratory parameters in obese patients with obstructive
sleep apnoea syndrome (OSAS). METHODS: Twenty consecutive obese male patients
fulfilling OSAS criteria at Karolinska University Hospital were randomized into
two groups. Intervention with an 8-week weight reduction programme consisting of
a low-calorie diet, together with group meetings, was evaluated compared to
expectancy alone for the control group, followed by a crossover. Follow-up at 3
months included anthropometrics and ambulant sleep apnoea recordings. RESULTS:
Eleven of twenty men completed the protocol. There were significant differences
between the intervention group (n = 6) and the control group (n = 5) in changes
of weight (p < 0.01) and oxygen desaturation index (ODI4) (p < 0.05). We also
found a significant positive correlation in these 11 males after the crossover
between their reduction in weight and their reduction in ODI4 (p < 0.05).
CONCLUSIONS: This pilot study indicates that weight reduction improves nocturnal
respiration in obese OSAS patients after 3 months' dietary treatment compared to
expectancy.
PMID- 24351731
TI - Our perception of weight: Socioeconomic and sociocultural explanations.
AB - SUMMARY: OBJECTIVE: To compare self-reported perception of weight with
biomedically measured body mass index in different socioeconomic and cultural
groups. METHOD: Of the original North West Adelaide Health (Cohort) Study (n =
4060) 68.5% (n = 2780) underwent a computer assisted telephone interview (CATI)
answering additional questions related to their social and health status. The
participants were asked "In terms of your weight, do you consider yourself to
be... too thin, a little thin, normal weight, a little overweight or very
overweight". The self-perception of weight was compared to biomedically measured
BMI (body mass index). Binary logistic regression was used to compare those
participants who were obese (BMI >= 30) with the self-perceived weight status of
'a little overweight'. The outcome measures included the Socioeconomic Indexes
for Areas Index of Relative Socioeconomic Disadvantage (SEIFA IRSD), country of
birth and household income. RESULTS: Of those that were underestimating their
obese weight status, 41.5% were male and 32.2% female. The highest
misclassification was for those who considered their weight to be 'a little
overweight', with 59.6% biomedically measured with a BMI of over 30. The odds of
being biomedically measured obese (BMI >= 30) were compared to those who
considered themselves to be 'a little overweight'. Those that misreported their
weight status and were biomedically obese, were more likely to be living in the
lowest quintile of disadvantage, have a household income of less then $20,000 or
be born in Eastern or Western Europe. CONCLUSION: There are psychosocial,
sociocultural and social environmental influences related to the perception of
weight status. Future research will need to understand the processes whereby
people are not aware they have a weight problem.
PMID- 24351732
TI - Projected future trends of hospital service use for selected obesity-related
conditions.
AB - SUMMARY: BACKGROUND: The duel problems of obesity and the aging of society are
likely to produce substantially increased demand on health services in the
future. We examine the projected burden which four obesity-related conditions
potentially can place on the hospital system in Australia: diabetes, obstructive
sleep apnoea (OSA), knee replacements, and bariatric surgery. METHODS:
Separations for each condition were obtained from the Australian Institute of
Health and Welfare (AIHW) data from 1990 to 2005. Projections of age specific
rates for each condition/procedure to 2020 by sex and 5-year age groups developed
using double exponential smoothing were applied to population projections to
estimate numbers of separations or procedures. RESULTS: Large, significant
increases in rates per 100,000 population for each condition/procedure occurred
from 1990 to 2005 for each gender and across all adult age groups. Numbers of
separations for diabetes are estimated to increase from 50,258 in 2005 to 180,057
in 2020 and for OSA from 32,262 to 83,535. Procedures for total knee replacements
are projected to increase from 28,490 in 2005 to 67,619 in 2020 and for bariatric
surgery from 32,262 to 83,535. CONCLUSION: The combined effects of demographic
change with a rapidly aging population along with a high and increasing
prevalence of obesity will continue to drive the four conditions/procedures
studied and this will have a considerable effect on health resources. The
consequences of not acting, or acting ineffectively, are high and constitute a
serious threat to future public health.
PMID- 24351733
TI - Risk factors of work disability in patients with inflammatory bowel disease--a
Dutch nationwide web-based survey: work disability in inflammatory bowel disease.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is associated with high costs to
society. Few data on the impact of IBD on work disability and potential
predictive factors are available. AIM: To assess the prevalence of and predictive
factors for work disability in Crohn's disease (CD) and ulcerative colitis (UC).
METHODS: A web-based questionnaire was sent out in seven university hospitals and
seven general hospitals in the Netherlands. Initially, 3050 adult IBD patients
were included in this prospective, nationwide cohort study, whereof 2629 patients
were within the working-age (18-64 years). We used the baseline questionnaire to
assess the prevalence rates of work disability in CD and UC patients within
working-age. Prevalence rates were compared with the Dutch background population
using age- and sex-matched data obtained from Statistics Netherlands.
Multivariable logistic regression analyses were performed to identify independent
demographic- and disease-specific risk factors for work disability. RESULTS: In
CD, 18.3% of patients was fully disabled and 8.8% partially disabled, compared to
9.5% and 5.4% in UC patients (p<0.01), respectively. Compared to Dutch controls,
the prevalence was significantly higher, especially in CD patients. Higher age,
low education, depression, chronic back pain, joint manifestations and typical
disease-related risk factors such as penetrating disease course and surgery in
the past were all found to be associated with work disability. CONCLUSION: We
report high work disability rates in a large sample of IBD patients in the
Netherlands. CD patients suffer more frequently from work disability than UC
patients. A combination of demographic and disease-related factors is predictive
of work disability.
PMID- 24351734
TI - Waterpipe smoking among middle and high school Jordanian students: patterns and
predictors.
AB - Despite the increase in attention to waterpipe tobacco smoking, the patterns and
predictors of this method of tobacco use among Jordanian youth are not well
known. The current study was conducted to assess the patterns and the predictors
of waterpipe tobacco smoking among school aged students in one of Jordan's
Central Governorates. A cross-sectional survey was conducted to investigate the
patterns and predictors of waterpipe tobacco smoking among youth (grades 6, 8, 10
and 12). Using a multistage random sampling more than 1,000 students was
selected. Data were collected using the Arabic Youth Tobacco Use Composite
Measure (YTUCM). Waterpipe smoking was assessed for "past 12 months", "past
month" and "past week". Students' ages ranged from 11 to 18 years, (mean age +/-
14.7; SD +/- 1.9 years). The percentage of girls who smoked waterpipe was greater
for all frequencies of use than it was for boys. Age, gender, and belief that
smoking makes more friends were predictors of smoking among study participants.
This is the first known study to examine waterpipe smoking among youth aged 11
and 12. Our findings illustrate the need for public health campaigns to reach and
educate youth, their families, teachers and school systems regarding the growing
recognized health risks of waterpipe smoking.
PMID- 24351735
TI - A review of national-level adaptation planning with regards to the risks posed by
climate change on infectious diseases in 14 OECD nations.
AB - Climate change is likely to have significant implications for human health,
particularly through alterations of the incidence, prevalence, and distribution
of infectious diseases. In the context of these risks, governments in high income
nations have begun developing strategies to reduce potential climate change
impacts and increase health system resilience (i.e., adaptation). In this paper,
we review and evaluate national-level adaptation planning in relation to
infectious disease risks in 14 OECD countries with respect to "best practices"
for adaptation identified in peer-reviewed literature. We find a number of
limitations to current planning, including negligible consideration of the needs
of vulnerable population groups, limited emphasis on local risks, and inadequate
attention to implementation logistics, such as available funding and timelines
for evaluation. The nature of planning documents varies widely between nations,
four of which currently lack adaptation plans. In those countries where planning
documents were available, adaptations were mainstreamed into existing public
health programs, and prioritized a sectoral, rather than multidisciplinary,
approach. The findings are consistent with other scholarship examining adaptation
planning indicating an ad hoc and fragmented process, and support the need for
enhanced attention to adaptation to infectious disease risks in public health
policy at a national level.
PMID- 24351736
TI - Can smartphones enhance telephone-based cognitive assessment (TBCA)?
AB - TBCA has emerged to solve the limitations of administering cognitive assessments
face-to-face. The recent development of telephones and knowledge advances in the
area of cognitive impairment may affect the development of TBCA. The purpose of
this paper is to discuss how smartphones can be used to enhance the applicability
of TBCA, which has previously been administered by conventional telephone. This
paper will first review, describe and critique the existing TBCA instruments. It
will then discuss the recent developments in tele-technology, the popularity of
tele-technology among the elderly, potential benefits and challenges in using
smartphones for cognitive assessment, and possible future developments in this
technology. In the systematic review, eighteen TBCA instruments were identified.
They were found to be valid in differentiating between people with and without
dementia. TBCA was previously found to be launched on a conventional telephone
platform. The advances in understanding of cognitive impairment may demand that
telephones be equipped with more advanced features. Recently, the development and
penetration of smartphones among the elderly has been rapid. This may allow the
smartphone to enhance its TBCA applicability by overcoming the limitations of the
conventional telephone, rendering the TBCA more efficient in addressing the
increasing demand and complexity of cognitive assessments in the future. However,
more research and technology developments are needed before smartphones can
become a valid platform for TBCA.
PMID- 24351737
TI - Nationwide surveillance for pathogenic microorganisms in groundwater near carcass
burials constructed in South Korea in 2010.
AB - Widespread outbreaks of foot-and-mouth disease and avian influenza occurred in
South Korea during 2010. In response to the culling of many animals to attenuate
the spread of disease, South Korea used mass burial sites to dispose of the large
number of carcasses; consequently, concerns about groundwater contamination by
leachate from these burial sites are increasing. Groundwater is one of the main
sources of drinking water, and its cleanliness is directly related to public
health. Thus, this study aimed to evaluate the safety of groundwater around the
burial sites (total of 600 sites). A total of 1,200 groundwater samples were
collected though the country, and microbial analysis was conducted during two
time periods: during the spring (n = 600; April to June 2012) and after rainfall
(n = 600; August to October, 2012; fall). Fecal coliform and Escherichia coli
were detected in 173 (14.4%) and 85 (7.1%) of the 1,200 samples, respectively.
Salmonella spp. and Shigella spp. each were detected only once (0.083%).
Clostridium perfringens was detected from 7 groundwater samples (0.583%), and E.
coli O157:H7 was not detected. With respect to norovirus, only the GII type was
detected from six groundwater samples (0.5%), and enterovirus was detected in 15
groundwater samples (1.25%). The frequency of E. coli that we detected was lower
than that found in previous studies conducted in South Korea, but we detected
higher frequency of fecal coliform than that observed in a previous report. The
contamination frequencies of Salmonella spp. and Shigella spp. were very low, but
C. perfringens, which could be an indicator of fecal pollution, was detected in
seven regions. Overall, the results of the present study indicate a low
possibility of contamination from burial sites. However, consistent monitoring is
required to prevent microbial contamination of groundwater near the burial sites.
PMID- 24351739
TI - Assessment of natural radioactivity levels of cements and cement composites in
the Slovak Republic.
AB - The radionuclide activities of 226Ra, 232Th and 40K and radiological parameters
(radium equivalent activity, gamma and alpha indices, the absorbed gamma dose
rate and external and internal hazard indices) of cements and cement composites
commonly used in the Slovak Republic have been studied in this paper. The cement
samples of 8 types of cements from Slovak cement plants and five types of
composites made from cement type CEM I were analyzed in the experiment. The
radionuclide activities in the cements ranged from 8.58-19.1 Bq.kg(-1), 9.78-26.3
Bq.kg(-1) and 156.5-489.4 Bq.kg(-1) for 226Ra, 232Th and 40K, respectively. The
radiological parameters in cement samples were calculated as follows: mean radium
equivalent activity Ra(eq) = 67.87 Bq.kg(-1), gamma index Igamma = 0.256, alpha
index Ialpha = 0.067, the absorbed gamma dose rate D = 60.76 nGy.h(-1), external
hazard index H(ex) = 0.182 and internal hazard index H(in) was 0.218. The
radionuclide activity in composites ranged from 6.84-10.8 Bq.kg(-1) for 226Ra,
13.1-20.5 Bq.kg(-1) for 232Th and 250.4-494.4 Bq.kg(-1) for 40K. The calculated
radiological parameters of cements were lower than calculated radiological
parameters of cement composites.
PMID- 24351738
TI - Increased pathogenicity of West Nile virus (WNV) by glycosylation of envelope
protein and seroprevalence of WNV in wild birds in Far Eastern Russia.
AB - In this review, we discuss the possibility that the glycosylation of West Nile
(WN) virus E-protein may be associated with enhanced pathogenicity and higher
replication of WN virus. The results indicate that E-protein glycosylation allows
the virus to multiply in a heat-stable manner and therefore, has a critical role
in enhanced viremic levels and virulence of WN virus in young-chick infection
model. The effect of the glycosylation of the E protein on the pathogenicity of
WN virus in young chicks was further investigated. The results indicate that
glycosylation of the WN virus E protein is important for viral multiplication in
peripheral organs and that it is associated with the strong pathogenicity of WN
virus in birds. The micro-focus reduction neutralization test (FRNT) in which a
large number of serum samples can be handled at once with a small volume (15 MUL)
of serum was useful for differential diagnosis between Japanese encephalitis and
WN virus infections in infected chicks. Serological investigation was performed
among wild birds in the Far Eastern region of Russia using the FRNT. Antibodies
specific to WN virus were detected in 21 samples of resident and migratory birds
out of 145 wild bird samples in the region.
PMID- 24351740
TI - Integrated human surveillance systems of West Nile virus infections in Italy: the
2012 experience.
AB - In Italy, a West Nile virus (WNV) surveillance plan was firstly implemented in
2008 and 2009 in two affected regions and, since 2010, according to a national
plan, a WNV neuroinvasive disease (WNND) surveillance has to be carried out each
year during the period 15 June-30 November, in those regions where WNV
circulation has been demonstrated among humans, animals or vectors. Moreover,
since WNV can be transmitted to humans even by blood transfusions and organ
transplants obtained from infected donors, the national surveillance integrates
the blood transfusions and organs transplant surveillances too. The paper
describes the results of this integrated human surveillance in Italy in 2012.
Overall, in 2012, 28 autochthonous confirmed cases of WNND were reported, 14
blood donations were found WNV positive by Nucleic Acid Amplification Test and no
solid organ donors tested positive for WNV. Moreover, 17 cases of WNV fever were
confirmed in Veneto region. When comparing the number of WNND cases reported to
the surveillance system in previous 4 years (43 cases during the period 2008
2011), with those reported in 2012 an important increase was observed in 2012.
The geographic distribution of human cases was consistent with the WNV
circulation among animals and vectors. Moreover, the implementation of preventive
measures for WNV transmission through blood components allowed the detection of
blood donors positive for WNV, avoiding the further spread of the disease. Since
surveillance strategies and preventive measures are based on the integration
among human, animal and vector control activities, the Italian experience could
be considered a good example of collaboration among different sectors of public
health in a "one health" perspective.
PMID- 24351741
TI - Characterising the smoking status and quit smoking behaviour of aboriginal health
workers in South Australia.
AB - The study objectives were to characterise the smoking status and quit smoking
behaviour of Aboriginal Health Workers (AHWs) in South Australia (SA), Australia;
and identify the psychosocial, socio-demographic, and household smoking
characteristics that distinguish smokers from quitters and never smokers. A self
reported cross-sectional survey was completed by AHWs in SA. Non-parametric
statistics were used for inferential analyses. Eighty-five AHWs completed surveys
representing a response rate of 63.0%. The prevalence of current smokers was
50.6%. Non-smokers (49.5%) included quitters (22.4%) and never smokers (27.1%).
Smoking status did not differ by gender or geographic location. Of current
smokers, 69.0% demonstrated a readiness to quit and 50.0% had made at least one
quit attempt in the last 12 months. Compared to quitters and never smokers,
current smokers expressed lower emotional wellbeing, and three times as many
resided with another smoker. Quitters had the highest levels of perceived social
support and part-time employment. A high proportion of AHWs who smoke desire, and
are ready to quit. Individual, social and household factors differentiated
smokers from non-smokers and quitters. Social support, and relationships and
structures that favour social support, are implicated as necessary to enable AHWs
who smoke to act on their desire to quit smoking.
PMID- 24351742
TI - Spatial autocorrelation of cancer incidence in Saudi Arabia.
AB - Little is known about the geographic distribution of common cancers in Saudi
Arabia. We explored the spatial incidence patterns of common cancers in Saudi
Arabia using spatial autocorrelation analyses, employing the global Moran's I and
Anselin's local Moran's I statistics to detect nonrandom incidence patterns.
Global ordinary least squares (OLS) regression and local geographically-weighted
regression (GWR) were applied to examine the spatial correlation of cancer
incidences at the city level. Population-based records of cancers diagnosed
between 1998 and 2004 were used. Male lung cancer and female breast cancer
exhibited positive statistically significant global Moran's I index values,
indicating a tendency toward clustering. The Anselin's local Moran's I analyses
revealed small significant clusters of lung cancer, prostate cancer and Hodgkin's
disease among males in the Eastern region and significant clusters of thyroid
cancers in females in the Eastern and Riyadh regions. Additionally, both
regression methods found significant associations among various cancers. For
example, OLS and GWR revealed significant spatial associations among NHL,
leukemia and Hodgkin's disease (r2 = 0.49-0.67 using OLS and r2 = 0.52-0.68 using
GWR) and between breast and prostate cancer (r2 = 0.53 OLS and 0.57 GWR) in Saudi
Arabian cities. These findings may help to generate etiologic hypotheses of
cancer causation and identify spatial anomalies in cancer incidence in Saudi
Arabia. Our findings should stimulate further research on the possible causes
underlying these clusters and associations.
PMID- 24351743
TI - Leptospirosis: a silent epidemic disease.
AB - This special issue of International Journal of Environmental Research and Public
Health is dedicated to leptospirosis, an endemic zoonotic disease that is a cause
of many acute undifferentiated fevers, especially in tropical countries. While it
can be debated whether leptospirosis is an emerging disease, it is evident that
it is becoming an emerging public health problem. It is recognized as a disease
of epidemic potential that has a significant health impact in many parts of the
world.
PMID- 24351745
TI - Prevalence of COPD and tobacco smoking in Tunisia--results from the BOLD study.
AB - In Tunisia, there is a paucity of population-based data on Chronic Obstructive
Pulmonary Disease (COPD) prevalence. To address this problem, we estimated the
prevalence of COPD following the Burden of Lung Disease Initiative. We surveyed
807 adults aged 40+ years and have collected information on respiratory history
and symptoms, risk factors for COPD and quality of life. Post-bronchodilator
spirometry was performed and COPD and its stages were defined according to the
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Six
hundred and sixty one (661) subjects were included in the final analysis. The
prevalence of GOLD Stage I and II or higher COPD were 7.8% and 4.2%, respectively
(Lower Limit of Normal modified stage I and II or higher COPD prevalence were
5.3% and 3.8%, respectively). COPD was more common in subjects aged 70+ years and
in those with a BMI < 20 kg/m2. Prevalence of stage I+ COPD was 2.3% in <10 pack
years smoked and 16.1% in 20+ pack years smoked. Only 3.5% of participants
reported doctor-diagnosed COPD. In this Tunisian population, the prevalence of
COPD is higher than reported before and higher than self-reported doctor
diagnosed COPD. In subjects with COPD, age is a much more powerful predictor of
lung function than smoking.
PMID- 24351744
TI - The potential link between gut microbiota and IgE-mediated food allergy in early
life.
AB - There has been a dramatic rise in the prevalence of IgE-mediated food allergy
over recent decades, particularly among infants and young children. The cause of
this increase is unknown but one putative factor is a change in the composition,
richness and balance of the microbiota that colonize the human gut during early
infancy. The coevolution of the human gastrointestinal tract and commensal
microbiota has resulted in a symbiotic relationship in which gut microbiota play
a vital role in early life immune development and function, as well as
maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is
associated with immune dysregulation and impaired gut epithelial integrity there
is substantial interest in the potential link between gut microbiota and food
allergy. Although the exact link between gut microbiota and food allergy is yet
to be established in humans, recent experimental evidence suggests that specific
patterns of gut microbiota colonization may influence the risk and manifestations
of food allergy. An understanding of the relationship between gut microbiota and
food allergy has the potential to inform both the prevention and treatment of
food allergy. In this paper we review the theory and evidence linking gut
microbiota and IgE-mediated food allergy in early life. We then consider the
implications and challenges for future research, including the techniques of
measuring and analyzing gut microbiota, and the types of studies required to
advance knowledge in the field.
PMID- 24351746
TI - Impact of flavour variability on electronic cigarette use experience: an internet
survey.
AB - BACKGROUND: A major characteristic of the electronic cigarette (EC) market is the
availability of a large number of different flavours. This has been criticised by
the public health authorities, some of whom believe that diverse flavours will
attract young users and that ECs are a gateway to smoking. At the same time,
several reports in the news media mention that the main purpose of flavour
marketing is to attract youngsters. The importance of flavourings and their
patterns of use by EC consumers have not been adequately evaluated, therefore,
the purpose of this survey was to examine and understand the impact of
flavourings in the EC experience of dedicated users. METHODS: A questionnaire was
prepared and uploaded in an online survey tool. EC users were asked to
participate irrespective of their current smoking status. Participants were
divided according to their smoking status at the time of participation in two
subgroups: former smokers and current smokers. RESULTS: In total, 4,618
participants were included in the analysis, with 4,515 reporting current smoking
status. The vast majority (91.1%) were former smokers, while current smokers had
reduced smoking consumption from 20 to 4 cigarettes per day. Both subgroups had a
median smoking history of 22 years and had been using ECs for 12 months. On
average they were using three different types of liquid flavours on a regular
basis, with former smokers switching between flavours more frequently compared to
current smokers; 69.2% of the former subgroup reported doing so on a daily basis
or within the day. Fruit flavours were more popular at the time of participation,
while tobacco flavours were more popular at initiation of EC use. On a scale from
1 (not at all important) to 5 (extremely important) participants answered that
variability of flavours was "very important" (score = 4) in their effort to
reduce or quit smoking. The majority reported that restricting variability will
make ECs less enjoyable and more boring, while 48.5% mentioned that it would
increase craving for cigarettes and 39.7% said that it would have been less
likely for them to reduce or quit smoking. The number of flavours used was
independently associated with smoking cessation. CONCLUSIONS: The results of this
survey of dedicated users indicate that flavours are marketed in order to satisfy
vapers' demand. They appear to contribute to both perceived pleasure and the
effort to reduce cigarette consumption or quit smoking. Due to the fact that
adoption of ECs by youngsters is currently minimal, it seems that implementing
regulatory restrictions to flavours could cause harm to current vapers while no
public health benefits would be observed in youngsters. Therefore, flavours
variability should be maintained; any potential future risk for youngsters being
attracted to ECs can be sufficiently minimized by strictly prohibiting EC sales
in this population group.
PMID- 24351747
TI - Elderly healthcare monitoring using an avatar-based 3D virtual environment.
AB - Homecare systems for elderly people are becoming increasingly important due to
both economic reasons as well as patients' preferences. Sensor-based surveillance
technologies are an expected future trend, but research so far has devoted little
attention to the User Interface (UI) design of such systems and the user-centric
design approach. In this paper, we explore the possibilities of an avatar-based
3D visualization system, which exploits wearable sensors and human activity
simulations. We present a technical prototype and the evaluation of alternative
concept designs for UIs based on a 3D virtual world. The evaluation was conducted
with homecare providers through focus groups and an online survey. Our results
show firstly that systems taking advantage of 3D virtual world visualization
techniques have potential especially due to the privacy preserving and simplified
information presentation style, and secondly that simple representations and
glancability should be emphasized in the design. The identified key use cases
highlight that avatar-based 3D presentations can be helpful if they provide an
overview as well as details on demand.
PMID- 24351748
TI - Tobacco retail outlets and vulnerable populations in Ontario, Canada.
AB - Interest has been increasing in regulating the location and number of tobacco
vendors as part of a comprehensive tobacco control program. The objective of this
paper is to examine the distribution of tobacco outlets in a large jurisdiction,
to assess: (1) whether tobacco outlets are more likely to be located in
vulnerable areas; and (2) what proportion of tobacco outlets are located close to
schools. Retail locations across the Province of Ontario from Ministry of Health
Promotion data were linked to 2006 Census data at the neighbourhood level. There
was one tobacco retail outlet for every 1,000 people over age 15 in Ontario.
Density of outlets varied by public health unit, and was associated with the
number of smokers. Tobacco outlets were more likely to be located in areas that
had high neighbourhood deprivation, in both rural and urban areas. Outlets were
less likely to be located in areas with high immigrant populations in urban
areas, with the reverse being true for rural areas. Overall, 65% of tobacco
retailers were located within 500 m of a school. The sale of tobacco products is
ubiquitous, however, neighbourhoods with lower socio-economic status are more
likely to have easier availability of tobacco products and most retailers are
located within walking distance of a school. The results suggest the importance
of policies to regulate the location of tobacco retail outlets.
PMID- 24351750
TI - Leuconostoc citreum MB1 as biocontrol agent of Listeria monocytogenes in milk.
AB - Cell-free supernatant from Leuconostoc citreum MB1 revealed specific
antilisterial activity. Preliminary studies demonstrated the proteinaceous, heat
stable, bacteriocin-like trait of the antimicrobial components present in the
supernatant. Determination of the genes encoding bacteriocins by PCR and DNA
sequencing led to amplification products highly homologous with leucocin A (found
in diverse Leuconostoc species) and UviB (found in Leuc. citreum KM20) sequences.
Additionally, antimicrobial activity of cell-free supernatant from Leuc. citreum
MB1 was revealed by an inhibition halo of the SDS-PAGE gel subjected to a direct
detection using Listeria monocytogenes as indicator strain. Different assays were
carried out to assess the capacity of Leuc.citreum MB1 to control List.
monocytogenes growth: (i) inactivation kinetics of the pathogen by antilisterial
compounds present in concentrated cell-free supernatant from Leuc. citreum MB1,
(ii) evaluation of optimal Leuc. citreum MB1 initial concentration to obtain
maximum List. monocytogenes ATCC 15313 inhibition, and (iii) biocontrol of List.
monocytogenes ATCC 15313 with Leuc. citreum MB1 during growth in milk at
refrigeration temperature. According to our results, it is unquestionable that at
least one bacteriocin is active in Leuc. citreum MB1, since important
antilisterial activity was verified either in its cell-free supernatant or in co
culture experiments. Co-culture tests showed that ~107 CFU/ml Leuc. citreum MB1
was the optimal initial concentration to obtain maximum pathogen inhibition.
Moreover, Leuc. citreum MB1 was able to delay List. monocytogenes growth at
refrigerated temperature.
PMID- 24351749
TI - The association between splenocyte apoptosis and alterations of Bax, Bcl-2 and
caspase-3 mRNA expression, and oxidative stress induced by dietary nickel
chloride in broilers.
AB - Two hundred and forty avian broilers were equally divided into four groups, and
raised with a corn-soybean basal diet or the same diet supplemented with 300,
600, 900 mg/kg NiCl2 for 42 days. Numbers or percentages of apoptotic splenocytes
by flow cytometry (FCM) and TUNEL were higher (p < 0.05 or p < 0.01) in the 300,
600 and 900 mg/kg groups than those in the control group. Results measured by qRT
PCR and ELISA showed that mRNA expression and contents were significantly higher
(p < 0.05 or p < 0.01) in Bax and Caspase-3, and were significantly lower (p <
0.05 or p < 0.01) in Bcl-2 of the 300, 600 and 900 mg/kg groups. Also, the SOD,
CAT and GSH-Px activities, and the ability to inhibit hydroxyl radical, and GSH
contents were significantly decreased (p < 0.05 or p < 0.01), and MDA contents
were increased (p < 0.05 or p < 0.01) in all groups. In conclusion, dietary NiCl2
in excess of 300 mg/kg caused apoptosis, altered Bax, Bcl-2 and Caspase-3 mRNA
expression levels and contents, and induced oxidative stress in the spleen. Also,
splenocyte apoptosis was closely related to the alternations of Bax, Bcl-2 and
Caspase-3 mRNA expression, and oxidative damage. The splenic immunity and blood
filtration functions were impaired in broilers.
PMID- 24351752
TI - APTA Combined Sections Meeting (CSM), Platform and Poster presentations, Feb 3-6,
2014, Las Vegas, NV.
PMID- 24351751
TI - Response category width as a psychophysical manifestation of construal level and
distance.
AB - The present research suggests that people adjust their mental response scales to
an object's distance and construal level. People make use of wider response
categories when they judge distant and abstract as compared with close and
concrete stimuli. Across five experiments, participants worked on visual and
verbal estimation problems (e.g., length or quantity judgments). Answers were
provided in interval format, and differences between minimal and maximal
estimates served as a measure of response category width. When target objects
were framed as spatially distant rather than close (Studies 1 and 3), as unlikely
rather than likely (Study 2), and as abstract rather than concrete (Study 4),
category widths increased. Similarly, priming a high-level rather than a low
level mindset yielded wider interval estimates (Study 5). The general discussion
highlights the usefulness of category width as a basic measure of construal level
and as a theoretical link between various branches of construal-level theory.
PMID- 24351753
TI - Antibodies to both terminal and internal B-cell epitopes of Francisella
tularensis O-polysaccharide produced by patients with tularemia.
AB - Francisella tularensis, the Gram-negative bacterium that causes tularemia, is
considered a potential bioterrorism threat due to its low infectivity dose and
the high morbidity and mortality from respiratory disease. We previously
characterized two mouse monoclonal antibodies (MAbs) specific for the O
polysaccharide (O antigen [OAg]) of F. tularensis lipopolysaccharide (LPS): Ab63,
which targets a terminal epitope at the nonreducing end of OAg, and Ab52, which
targets a repeating internal OAg epitope. These two MAbs were protective in a
mouse model of respiratory tularemia. To determine whether these epitope types
are also targeted by humans, we tested the ability of each of 18 blood serum
samples from 11 tularemia patients to inhibit the binding of Ab63 or Ab52 to F.
tularensis LPS in a competition enzyme-linked immunosorbent assay (ELISA).
Although all serum samples had Ab63- and Ab52-inhibitory activities, the ratios
of Ab63 to Ab52 inhibitory potencies varied 75-fold. However, the variation was
only 2.3-fold for sequential serum samples from the same patient, indicating
different distributions of terminal- versus internal-binding antibodies in
different individuals. Western blot analysis using class-specific anti-human Ig
secondary antibodies showed that both terminal- and internal-binding OAg
antibodies were of the IgG, IgM, and IgA isotypes. These results support the use
of a mouse model to discover protective B-cell epitopes for tularemia vaccines or
prophylactic/therapeutic antibodies, and they present a general strategy for
interrogating the antibody responses of patients and vaccinees to microbial
carbohydrate epitopes that have been characterized in experimental animals.
PMID- 24351754
TI - Cytotoxic T cell adoptive immunotherapy as a treatment for nasopharyngeal
carcinoma.
AB - Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We
assess the safety and tolerability of adoptive transfer of autologous cytotoxic T
lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a
patient with recurrent NPC. After infusion, the majority of pulmonary lesions
were no longer evident, although the primary tumor did not regress.
PMID- 24351755
TI - Novel catanionic surfactant vesicle vaccines protect against Francisella
tularensis LVS and confer significant partial protection against F. tularensis
Schu S4 strain.
AB - Francisella tularensis is a Gram-negative immune-evasive coccobacillus that
causes tularemia in humans and animals. A safe and efficacious vaccine that is
protective against multiple F. tularensis strains has yet to be developed. In
this study, we tested a novel vaccine approach using artificial pathogens,
synthetic nanoparticles made from catanionic surfactant vesicles that are
functionalized by the incorporation of either F. tularensis type B live vaccine
strain (F. tularensis LVS [LVS-V]) or F. tularensis type A Schu S4 strain (F.
tularensis Schu S4 [Schu S4-V]) components. The immunization of C57BL/6 mice with
"bare" vesicles, which did not express F. tularensis components, partially
protected against F. tularensis LVS, presumably through activation of the innate
immune response, and yet it failed to protect against the F. tularensis Schu S4
strain. In contrast, immunization with LVS-V fully protected mice against
intraperitoneal (i.p.) F. tularensis LVS challenge, while immunization of mice
with either LVS-V or Schu S4-V partially protected C57BL/6 mice against an
intranasal (i.n.) F. tularensis Schu S4 challenge and significantly increased the
mean time to death for nonsurvivors, particularly following the i.n. and
heterologous (i.e., i.p./i.n.) routes of immunization. LVS-V immunization, but
not immunization with empty vesicles, elicited high levels of IgG against
nonlipopolysaccharide (non-LPS) epitopes that were increased after F. tularensis
LVS challenge and significantly increased early cytokine production. Antisera
from LVS-V-immunized mice conferred passive protection against challenge with F.
tularensis LVS. Together, these data indicate that functionalized catanionic
surfactant vesicles represent an important and novel tool for the development of
a safe and effective F. tularensis subunit vaccine and may be applicable for use
with other pathogens.
PMID- 24351758
TI - Assessment of proficiency and competency in laboratory animal biomethodologies.
AB - Personnel working with laboratory animals are required by laws and guidelines to
be trained and qualified to perform biomethodologic procedures. The assessment of
competency and proficiency is a vital component of a laboratory animal training
program, because this process confirms that the trainees have met the learning
objectives for a particular procedure. The approach toward qualification
assessment differs between organizations because laws and guidelines do not
outline how the assessment should be performed or which methods and tools should
be used. Assessment of clinical and surgical medicine has received considerable
attention over the last few decades and has progressed from simple subjective
methods to well-defined and objective methods of assessing competency. Although
biomethodology competency and proficiency assessment is discussed in the
literature, a standard and objective assessment method has not yet been
developed. The development and implementation of an objective and standardized
biomethodologic assessment program can serve as a tool to improve standards,
ensure consistent training, and decrease research variables yet ensure animal
welfare. Here we review the definition and goals of training and assessment,
review assessment methods, and propose a method to develop a standard and
objective assessment program for the laboratory animal science field,
particularly training departments and IACUC.
PMID- 24351756
TI - Neisseria meningitidis native outer membrane vesicles containing different
lipopolysaccharide glycoforms as adjuvants for meningococcal and nonmeningococcal
antigens.
AB - We evaluated the adjuvant effect of a modified glycoform of lipopolysaccharide
(LPS) (LgtB-LpxL1) compared to that of the nonmodified glycoform Lpxl1 serogroup
B meningococcal H44/76 native outer membrane vesicles (nOMVs) on immune responses
to vaccination with the recombinant meningococcal protein, rPorA, tetanus toxoid,
or meningococcal serogroup C capsular polysaccharide. We used LgtB-LpxL1 LPS
because the disruption of the lgtB gene, which results in the exposure of N
acetylglucosamine-galactose-glucose residues in the LPS outer core, has been
shown to enhance the activation of human dendritic cells in vitro. The responses
were compared to those of a monophosphoryl lipid A (MPL)-based adjuvant and to an
aluminum hydroxide suspension. The nOMVs induced blood serum IgG responses
against each of the three antigens comparable to those obtained with MPL or
aluminum salt. However, nOMVs elicited (i) a lower IgG1/IgG2a ratio against rPorA
and (ii) serum bactericidal antibody titers superior to those achieved with
aluminum salt, reaching similar titers to those obtained with MPL. Similarly,
bactericidal antibody titers induced by immunization with meningococcal serogroup
C polysaccharide and nOMVs were similar to those obtained using MPL but were
better than those with aluminum salt. Immunization with tetanus toxoid and nOMVs
resulted in tetanus toxoid-specific IgG responses similar to those obtained when
adjuvanted with aluminum salt. These results highlight the potential utility of
meningococcal LpxL1 LPS-containing nOMVs as an adjuvant for recombinant
meningococcal protein vaccines and suggest their possible use with a variety of
other antigens.
PMID- 24351759
TI - Standard operating procedures for maintaining cleanliness in a novel compact
facility for breeding SPF mice.
AB - A compact facility for SPF mice that was not equipped with a large autoclave used
disposable mouse cages instead. The SPF clean room was 5.7 * 8.1 * 2.7 m(3), with
a breeding capacity of 1008 cages (168 cages on each of 6 racks). We evaluated
cleanliness in the SPF clean room under the conditions of an occupation rate of
60% to 70% and typically 1 to 3 personnel (maximum, 4 to 6) daily on weekdays.
Personnel were taught standard procedures and received training beforehand.
During the 15-mo study period, the maximal concentration of airborne particles
0.5 MUm or larger was 1.0 * 10(4) particles/m3 and that of particles 5.0 MUm or
larger was 5.0 * 10(2) particles/m(3)--well below the maximal permissible
concentrations of 3.52 * 10(5) and 2.93 * 10(3) particles/m(3), respectively.
During the study period, no mice exhibited clinical symptoms of infection.
Testing of 2 representative, overtly healthy mice for 16 pathogens including
Staphylococcus aureus, Pseudomonas aeruginosa, and Helicobacter bilis failed to
detect any of the target agents. The current study demonstrates the feasibility
of the compact facility for breeding SPF mice in the academic environment.
PMID- 24351757
TI - Multiepitope fusion antigen induces broadly protective antibodies that prevent
adherence of Escherichia coli strains expressing colonization factor antigen I
(CFA/I), CFA/II, and CFA/IV.
AB - Diarrhea is the second leading cause of death in children younger than 5 years
and continues to be a major threat to global health. Enterotoxigenic Escherichia
coli (ETEC) strains are the most common bacteria causing diarrhea in developing
countries. ETEC strains are able to attach to host small intestinal epithelial
cells by using bacterial colonization factor antigen (CFA) adhesins. This
attachment helps to initiate the diarrheal disease. Vaccines that induce
antiadhesin immunity to block adherence of ETEC strains that express
immunologically heterogeneous CFA adhesins are expected to protect against ETEC
diarrhea. In this study, we created a CFA multiepitope fusion antigen (MEFA)
carrying representative epitopes of CFA/I, CFA/II (CS1, CS2, and CS3), and CFA/IV
(CS4, CS5, and CS6), examined its immunogenicity in mice, and assessed the
potential of this MEFA as an antiadhesin vaccine against ETEC. Mice
intraperitoneally immunized with this CFA MEFA exhibited no adverse effects and
developed immune responses to CFA/I, CFA/II, and CFA/IV adhesins. Moreover, after
incubation with serum of the immunized mice, ETEC or E. coli strains expressing
CFA/I, CFA/II, or CFA/IV adhesins were significantly inhibited in adherence to
Caco-2 cells. Our results indicated this CFA MEFA elicited antibodies that not
only cross-reacted to CFA/I, CFA/II and CFA/IV adhesins but also broadly
inhibited adherence of E. coli strains expressing these seven adhesins and
suggested that this CFA MEFA could be a candidate to induce broad-spectrum
antiadhesin protection against ETEC diarrhea. Additionally, this antigen
construction approach (creating an MEFA) may be generally used in vaccine
development against heterogenic pathogens.
PMID- 24351760
TI - Survey of laboratory animal technicians in the United States for Coxiella
burnetii antibodies and exploration of risk factors for exposure.
AB - Little is known about the prevalence of zoonotic infections among laboratory
animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is
a known occupational hazard for persons caring for livestock. We sought to
determine the seroprevalence of C. burnetii antibodies among LAT and to identify
risk factors associated with C. burnetii seropositivity. A survey was
administered and serum samples collected from a convenience sample of 97 LAT.
Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody
assays for phase I and phase II IgG were used to confirm the status of samples
that were positive or equivocal by ELISA; positive samples were titered to
endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97
respondents. In our sample of LAT, seropositivity to C. burnetii was therefore
twice as high in LAT as compared with the general population. Age, sex, and
working with sheep regularly were not associated with seropositivity. Risk
factors associated with seropositivity included breeding cattle within
respondent's research facility, any current job contact with waste from beef
cattle or goats, and exposure to animal waste during previous jobs or outside of
current job duties. Only 15% of responding LAT reported being aware that sheep,
goats, and cattle can transmit Q fever. Research facilities that use cattle or
goats should evaluate their waste-management practices and educational programs
in light of these findings. Additional efforts are needed to increase awareness
among LAT regarding Q fever and heightened risk of exposure to infectious
materials. Physicians should consider the risk of infection with C. burnetii when
treating LAT with potential occupational exposures.
PMID- 24351761
TI - Short-term storage of rat sperm in the presence of various extenders.
AB - Sperm preservation protocols differ among animal species because of different
sperm characteristics among species. Rat sperm have extreme sensitivity to
suboptimal conditions in centrifugation, pipetting and chilling due to their
longer tail, the shape and size of the sperm head, and membrane composition. The
aim of this study was to determine optimal conditions for short-term storage of
rat sperm by evaluating their motility and membrane and acrosomal integrity in
response to various extender solutions, temperatures, and durations. Motility of
rat sperm was highest when stored at 22 degrees C; motility was 28% and 14% at
72 h in TL-HEPES and PBS extenders, respectively. The motility and membrane
integrity of rat sperm fell significantly within 24 h at 4 and 37 degrees C.
Although cold storage did not have a detrimental effect on acrosomal integrity of
sperm, room temperature storage reduced acrosomal integrity after 24 h. LEY
extender caused the highest loss in acrosomal integrity at 48 and 72 h. In
conclusion, storage at 4 or 37 degrees C reduced the motility and membrane
integrity of rat sperm even with short incubation periods. Rat sperm stored in TL
HEPES or PBS remained motile for at least 3 d when held at 22 degrees C.
PMID- 24351762
TI - Individually ventilated cages impose cold stress on laboratory mice: a source of
systemic experimental variability.
AB - Individual ventilated cages (IVC) are increasing in popularity. Although mice
avoid IVC in preference testing, they show no aversion when provided additional
nesting material or the cage is not ventilated. Given the high ventilation rate
in IVC, we developed 3 hypotheses: that mice housed in IVC experience more cold
stress than do mice housed in static cages; that IVC-induced cold stress affects
the results of experiments using mice; and that, when provided shelters, mice
behaviorally thermoregulate and thereby rescue the cold-stress effects of IVC. To
test these hypotheses, we housed mice in IVC, IVC with shelters, and static cages
maintained at 20 to 21 degrees C. We quantified the cold stress of each housing
system on mice by assessing nonshivering thermogenesis and brown adipose
vacuolation. To test housing effects in a common, murine model of human disease,
we implanted mice with subcutaneous epidermoid carcinoma cells and quantified
tumor growth, tumor metabolism, and adrenal weight. Mice housed in IVC had
histologic signs of cold stress and significantly higher nonshivering
thermogenesis, smaller subcutaneous tumors, lower tumor metabolism, and larger
adrenal weights than did mice in static cages. Shelters rescued IVC-induced
nonshivering thermogenesis, adrenal enlargement, and phenotype-dependent cold
mediated histologic changes in brown adipose tissue and tumor size. IVC impose
chronic cold stress on mice, alter experimental results, and are a source of
systemic confounders throughout rodent-dependent research. Allowing mice to
exhibit behavioral thermoregulation through seeking shelter markedly rescues the
experiment-altering effects of housing-imposed cold stress, improves physiologic
uniformity, and increases experimental reproducibility across housing systems.
PMID- 24351763
TI - Effect of spectral transmittance through red-tinted rodent cages on circadian
metabolism and physiology in nude rats.
AB - Light entrains normal circadian rhythms of physiology and metabolism in all
mammals. Previous studies from our laboratory demonstrated that spectral
transmittance (color) of light passing through cages affects these responses in
rats. Here, we addressed the hypothesis that red tint alters the circadian
nocturnal melatonin signal and circadian oscillation of other metabolic and
physiologic functions. Female nude rats (Hsd:RH-Foxn1(rnu); n = 12 per group)
were maintained on a 12:12-h light (300 lx; 123.0 MUW/cm(2); lights on 0600):dark
regimen in standard polycarbonate translucent clear or red-tinted cages. After 1
wk, rats underwent 6 low-volume blood draws via cardiocentesis over a 4-wk
period. Plasma melatonin levels were low during the light phase (1.0 +/- 0.2
pg/mL) in rats in both types of cages but were significantly lower in red-tinted
(105.0 +/- 2.4 pg/mL) compared with clear (154.8 +/- 3.8 pg/mL) cages during the
dark. Normal circadian rhythm of plasma total fatty acid was identical between
groups. Although phase relationships of circadian rhythms in glucose, lactic
acid, pO2, and pCO2 were identical between groups, the levels of these analytes
were lower in rats in red-tinted compared with clear cages. Circadian rhythms of
plasma corticosterone, insulin, and leptin were altered in terms of phasing,
amplitude, and duration in rats in red-tinted compared with clear cages. These
findings indicate that spectral transmittance through red-colored cages
significantly affects circadian regulation of neuroendocrine, metabolic, and
physiologic parameters, potentially influencing both laboratory animal health and
wellbeing and scientific outcomes.
PMID- 24351764
TI - Using snacks high in fat and protein to improve glucoregulatory function in
adolescent male marmosets (Callithrix jacchus).
AB - The common marmoset (Callithrix jacchus), a laboratory nonhuman primate, is a
well-known model of several human diseases and conditions, but the nutritional
needs of these animals are not fully understood. Here we describe a 4-mo
controlled study in which we increased the dietary fat and protein of subadult
male common marmosets by using healthy snacks. Six male marmosets received their
normal diet (control), and an additional 6 were given their normal diet
supplemented daily with a 14-kcal snack. Cashews and waxworms were used as the
snack, given their high-fat content. Although body weight did not differ between
the 2 groups, only control male marmosets showed increased chest circumferences
over the course of the study. Glucoregulatory function remained consistent in the
snack-fed marmosets, whereas control animals had progressed toward higher
insulin. Other indices of glucoregulation indicated significant differences in
adiponectin and the cortisol:cortisone ratio between the 2 groups, but no
differences in lipid concentration were detected. Therefore, the most notable
difference attributable to the snack feeding was improved glucoregulation.
Because the snacks we used had a high proportion of unsaturated compared with
saturated fat, we suggest that these healthy high-fat-high-protein snacks provide
an important contribution to the nutrition of this laboratory species. This study
also demonstrates the utility of marmosets as a model for understanding the
implications of dietary fats in humans.
PMID- 24351765
TI - Efficacy of direct detection of pathogens in naturally infected mice by using a
high-density PCR array.
AB - We used a high-density array of real-time PCR assays for commonly reported rodent
infectious agents (PRIA) to test naturally infected index mice and sentinel mice
exposed by contact and soiled-bedding transfer. PRIA detected 14 pathogens-
including viruses, bacteria, fur mites, pinworms, and enteric protozoa--in 97.2%
of 28 pooled fecal samples, fur-perianal swabs, and oral swabs from 4 cages
containing a total of 10 index mice. Among these pathogens, PRIA (like
conventional health monitoring methods) failed to detect Mycoplasma pulmonis,
Pasteurella pneumotropica, and Giardia spp. in all of the 9 contact and 9 soiled
bedding sentinels. PRIA demonstrated murine adenovirus and Cryptosporidium and
Spironucleus spp. in contact but not soiled-bedding sentinels and detected
Helicobacter and pinworms in fewer than half of the soiled-bedding sentinels. Of
the 4 species of Helicobacter that species-specific PCR assays identified in
index mice, only H. ganmani was found in soiled-bedding and contact sentinels.
PRIA detected all of the pathogens in sentinels that were identified by
conventional methods. Myobia musculi was detected by PCR in index and sentinel
mice but missed by conventional parasitologic examinations. In summary, PRIA
reproducibly detected diverse pathogens in heavily pooled specimens collected
noninvasively from infected index mice antemortem. The inability of PRIA and
conventional health monitoring methods (that is, parasitology, micro-biology, and
serology) to demonstrate transmission of some pathogens to contact sentinels and
the inefficient transmission of others to soiled-bedding sentinels underscores
the importance of direct PCR testing to determine the pathogen status of rodents
in quarantine and during routine colony surveillance.
PMID- 24351766
TI - Evaluation of diagnostic methods for Myocoptes musculinus according to age and
treatment status of mice (Mus musculus).
AB - Detecting and controlling murine fur mites continues to be challenging. Here we
compared the efficacy of fur-pluck, cage PCR, and fur PCR testing of mice
naturally infested with Myocoptes musculinus and make recommendations regarding
the application of these diagnostic strategies in aged or treated mice. We
compared all 3 diagnostic methods in groups of infested and noninfested control
mice over time. For fur plucks, we used a scoring system to quantitatively
compare mite infestations across ages. Mice that were 4 wk old had higher egg and
mite scores than did older mice, with average scores at 4 wk corresponding to 40
to 100 individual fur mites and eggs per sample. Furthermore, 15% and 20% of
samples from infested mice at 24 and 28 wk of age, respectively, lacked all fur
mites and eggs. Cage PCR results varied as mice grew older. Fur PCR testing was
the most sensitive and specific assay in untreated infested mice, particularly
when mite densities were low. In addition, we compared fur-pluck and fur PCR
tests for evaluating the efficacy of selamectin treatment. Two treatments with
selamectin eliminated Myocoptes fur-mite infestations. At 8 wk after treatment,
all fur-pluck samples were negative, but one-third of treated infested cages
remained positive by fur PCR assay; at 16 wk after treatment, all cages were
negative by fur PCR assay. Because offspring of infested mice were invariably
heavily infested, breeding of suspected infested mice with subsequent testing of
offspring was the definitive testing strategy when fur-pluck and PCR results
conflicted.
PMID- 24351767
TI - Incidence rates of spontaneous disease in laboratory mice used at a large
biomedical research institution.
AB - A detailed epidemiologic survey of spontaneous diseases of mice used in
biomedical research has not been performed in more than 4 decades. The current
study examined all mouse disease reports for a subset of the University of
Pennsylvania vivaria from October 2010 through September 2011. Mortality logs
were examined over the same period of time. After eliminating protocol-related
cases, the incidence rates for more than 30 diseases were calculated in terms of
number of cases per 1000 cages per month. The average daily census for the
facilities analyzed exceeded 29,000 cages and included more than 180 research
groups. No single research group accounted for more than 4% of the total number
of cases reported, indicating that this study did not simply quantify the
spontaneous disease incidence in a limited number of research groups. Spontaneous
mortality with unknown cause in adult and neonatal mice without prior reported
illness was the most commonly reported issue, followed by dermatitis, ocular
disease, and nonspecific clinical signs including lethargy, poor hair coat, and
muscle wasting. These results indicate that improving the ability to identify
sick mice is important in refining the care and use of mice in biomedical
research. The information provided in the current study can help to provide a
baseline for comparison, guide the field in directing mouse welfare research
toward areas of need, and identify optimal methods of care for mice in biomedical
research.
PMID- 24351768
TI - Underwater anesthesia of diamondback terrapins (Malaclemys terrapin) for
measurement of auditory evoked potentials.
AB - Investigations into the biology of aquatic and semiaquatic species, including
those involving sensory specialization, often require creative solutions to novel
questions. We developed a technique for safely anesthetizing a semiaquatic
chelonian species, the diamondback terrapin (Malaclemys terrapin), for
measurement of auditory evoked potentials while animals were completely submerged
in water. Custom-modified endotracheal tubes were used to obtain a watertight
seal on both sides of the glottis and prevent aspiration of water during testing.
No adverse effects were seen after the procedures, and assessment of venous blood
gas partial pressures and lactate concentrations indicated that sufficient gas
exchange was maintained under anesthesia through manual ventilation.
PMID- 24351769
TI - 3D-2D registration for surgical guidance: effect of projection view angles on
registration accuracy.
AB - An algorithm for intensity-based 3D-2D registration of CT and x-ray projections
is evaluated, specifically using single- or dual-projection views to provide 3D
localization. The registration framework employs the gradient information
similarity metric and covariance matrix adaptation evolution strategy to solve
for the patient pose in six degrees of freedom. Registration performance was
evaluated in an anthropomorphic phantom and cadaver, using C-arm projection views
acquired at angular separation, Deltatheta, ranging from ~0 degrees -180 degrees
at variable C-arm magnification. Registration accuracy was assessed in terms of
2D projection distance error and 3D target registration error (TRE) and compared
to that of an electromagnetic (EM) tracker. The results indicate that angular
separation as small as Deltatheta ~10 degrees -20 degrees achieved TRE <2 mm
with 95% confidence, comparable or superior to that of the EM tracker. The method
allows direct registration of preoperative CT and planning data to intraoperative
fluoroscopy, providing 3D localization free from conventional limitations
associated with external fiducial markers, stereotactic frames, trackers and
manual registration.
PMID- 24351770
TI - Health in a 'post-transition' Australia: adding years to life or life to years?
AB - OBJECTIVE: To explore the likely impact of future trajectories of morbidity and
mortality in Australia. METHODS: Estimates of mortality and morbidity were
obtained from a previous assessment of Australia's health from 1993 to 2003,
including projections to 2023. Outcomes of interest were the difference between
life expectancy (LE0) and health-adjusted life expectancy (i.e. absolute lost
health expectancy (ALHE0)), ALHE0 as a proportion of LE0 and the partitioning of
changes in ALHE0 into additive contributions from changes in age- and cause
specific mortality and morbidity. RESULTS: Actual and projected trajectories of
mortality and morbidity resulted in an expansion of ALHE0 of 1.22 years between
1993 and 2023, which was equivalent to a relative expansion of 0.7% in morbidity
over the life course. Most (93.8%) of this expansion was accounted for by
cardiovascular disease, diabetes and cancer; of these, the only unfavourable
trend of any note was increasing morbidity from diabetes. CONCLUSIONS: Time spent
with morbidity will most likely increase in terms of numbers of years lived and
as a proportion of the average life span. This conclusion is based on the
expectation that gains in LE0 will continue to exceed gains in ALHE0, and has
important implications for public policy. WHAT IS KNOWN ABOUT THE TOPIC? Although
the aging of Australia's population as a result of declining birth and death
rates is well understood, its relationship with levels of morbidity is not always
fully appreciated. This is most noticeable in the policy discourse on primary
prevention, in which such activities are sometimes portrayed as having unrealised
potential with respect to alleviating growth in health service demand. WHAT DOES
THIS PAPER ADD? This paper sheds new light on these relationships by exploring
the likely impact of future trajectories of both morbidity and mortality within
an additive partitioning framework. The results suggest a modest expansion of
morbidity over the life course, most of which is accounted for by only three
causes. In two of these (cardiovascular disease and cancer), the underlying
trends in both mortality and morbidity have been favourable for some time due, at
least in part, to success in primary prevention. WHAT ARE THE IMPLICATIONS FOR
PRACTITIONERS? Although there may be good arguments in favour of a greater focus
on primary prevention as currently practiced, reducing overall demand for health
services is unlikely to be one of them. To make such an argument valid, policy
makers should consider shifting their attention to the effectiveness of primary
prevention as it relates to causes other than cardiovascular disease and cancer,
particularly those with a predominantly non-fatal impact, such as diabetes and
degenerative diseases of old age.
PMID- 24351771
TI - Weight reduction and maintenance in a specialized outpatient health care center.
AB - SUMMARY: OBJECTIVE: To prospectively evaluate the amount of weight loss and
subsequent maintenance and to identify correlates of successful weight reduction
in overweight and obese outpatients treated in a specialized health care center.
TREATMENT: A treatment program involving diet, exercise and behavior modification
was provided in an outpatient setting. Twenty-four treatment courses with a total
of 177 participants (age: 45.5 +/- 12.2 year; BMI: 36.7 +/- 5.6 kg/m(2)) were
run. MEASUREMENTS: Weight and baseline characteristics were recorded at start of
program; weight was re-assessed at the end of treatment and 1 year after the end
of treatment. RESULTS: Patients achieved a significant weight loss of 5.6 +/- 7.9
kg (5.1 +/- 6.4% of initial body weight) in the course of 1 year. An average of
80.8% or 4.8 kg of initial weight loss was maintained a year after treatment,
representing a significant weight regain. A higher initial BMI, intake of
venlafaxin, a higher percentage of course attendance, course completion and
hypertension were associated with greater weight loss. The interaction of the
specific treatment course and the percentage of attendance explained 25% of the
variance of percental total weight loss. CONCLUSION: Significant weight losses
can be achieved by overweight and obese patients after a treatment program in
specialized health care addressing diet, exercise and behavioral aspects. Weight
loss maintenance remains difficult for patients. The specific treatment group
itself and attendance of course sessions are critical for weight loss and should
be considered in the design and evaluation of group-based treatment programs.
PMID- 24351772
TI - Quality of life after gastric banding in morbidly obese Dutch patients: Long-term
follow-up.
AB - SUMMARY: OBJECTIVE: Long-term effects of adjustable gastric banding (AGB) on
quality of life (QoL) in a morbidly obese population were investigated in a cross
sectional study. Additionally, determinants of QoL after AGB were assessed.
METHODS: All patients treated by AGB for morbid obesity in a Dutch hospital were
invited to complete the RAND 36-Item Health Survey. Of 121 participating patients
59 met the criteria for long-term follow-up (>5 years): 4 male and 55 female,
mean age 42.4 +/- 9.7 years, mean body mass index (BMI) before surgery 44.9 +/-
5.9 kg/m(2). Time since surgery was 74.7 months (range 60-107.6). The control
group consisted of 28 presurgical patients. General and obesity-related
parameters were assessed for correlation with QoL. RESULTS: Significant
differences between the preoperative group and Dutch community norm (CN) values
were found on five out of eight QoL subscales, in favor of CN. AGB induced
significant weight loss in the postoperative group: 56.1% excess weight loss
(%EWL). This group scored significantly better than the preoperative group on one
out of eight subscales: physical functioning (P = 0.019). Additionally, scores on
four out of eight subscales were still significantly impaired compared to CN.
Postoperative BMI and %EWL influenced QoL after long-term follow-up, whereas
weight regain had no negative impact. CONCLUSIONS: This study shows that after
long-term follow-up subjects treated by gastric banding to induce weight loss
have a slightly better QoL than those who did not undergo surgery yet. QoL
remains impaired in comparison to the general population. After long-term follow
up BMI and weight loss do influence QoL whereas weight regain does not have any
negative impact.
PMID- 24351773
TI - High-fat diet-induced obesity is attenuated by probiotic strain Lactobacillus
paracasei ST11 (NCC2461) in rats.
AB - SUMMARY: In a recent study, we obtained some evidences that probiotic strain
Lactobacillus affects the autonomic nerve activities and regulates blood glucose
and cardiovascular function. In the study presented here, we found that long-term
ingestion of the lactobacillus strain Lactobacillus paracasei ST11 (NCC2461)
reduced body weight and abdominal fat weight. To investigate possible role of
autonomic nerves in anti-obesity action of NCC2461, we examined the effects of
intraduodenal (ID) injection of the lactobacillus strain L. paracasei ST11
(NCC2461) on sympathetic nerve activity innervating white adipose tissue (WAT
SNA) in urethane-anesthetized rats, and found that it accelerated WAT-SNA.
Moreover, intraduodenal (ID) injection of NCC2461 increased in sympathetic nerve
activity innervating brown adipose tissue (BAT-SNA) and decreased in hepatic
vagal nerve activity (HVNA). In addition, using conscious rats, we examined the
effects of intra-gastric (IG) injection of NCC2461 on lipolysis and BAT
thermogenesis, and observed that it clearly elevated the plasma FFA level, BAT
temperature and abdominal temperature. Thus, these data suggest that the NCC2461
affects autonomic nerves, enhances lipolysis, and reduces body weight in rats.:
PMID- 24351774
TI - Cutoff point of waist circumference for the diagnosis of metabolic syndrome in an
Iranian population.
AB - SUMMARY: BACKGROUND: Proposed cutoffs for waist circumference (WC) in western
populations may be not appropriate for Asian populations. The published data
among Iranians are insufficient to address this issue. This study was designed to
identify cutoffs for WC that confer increased risk of metabolic syndrome in
Iranian adults living in Zanjan, a province located in the west of Tehran.
MATERIALS AND METHODS: Data of a cross-sectional sample of 3277 Iranian adults
aged more than 20 years were analyzed. In the original study individual body
weight, height, WC, and blood pressure were assessed and fasting plasma glucose,
triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol
were measured. After excluding WC, existence of two or more of the remaining four
risk factors of the modified NCEP III criteria for metabolic syndrome were
defined as multiple risk factors. Receiver operating characteristic (ROC)
analysis was used to find out the optimal cutoff values of WC to predict
metabolic syndrome. RESULTS: The cutoff level yielding the maximal sensitivity
and specificity for predicting the presence of metabolic syndrome (multiple risk
factors) was 87 cm in men and 82 cm in women. Cutoffs corresponding to body mass
index (BMI) 25 and 30 kg/m(2) to predict metabolic syndrome were 84 and 97 cm in
men and 78 and 91 cm in women, respectively. CONCLUSIONS: Lower cutoffs for WC
should be considered in the identification of Iranian population at high risk of
metabolic syndrome.
PMID- 24351775
TI - Parental obesity as a predictor of childhood overweight/obesity in Australian
migrant children.
AB - SUMMARY: Obesity levels are increasing disproportionately in immigrant children
worldwide. We investigated predictors of immigrant children's obesity status in a
well-documented 3-year follow-up study of children at 9 years (n = 1232) and 12
years (n = 628) of age living in inner city areas of Sydney (Australia). The
major immigrant groups in this sample were from Europe, the Middle East and SE
Asia. Having an obese parent and having either parent or child not being born in
Australia and not playing organised sport were predictors of childhood obesity.
If either parent was obese compared to non-obese, then the odds ratio for a 9
year-old child of being obese compared to normal weight was 4.9 (95% CI: 3.0
8.0); for 12-year olds the odds ratio was 8.0 (95% CI: 3.6-18). For the survey of
9-years old, a parent born outside Australia or if the child himself was born
outside Australia was associated with an almost twofold chance of being obese (OR
= 1.8, 95% CI: 1.1-3.0), and not participating in organised sports was
significantly associated with childhood obesity. Nine-year olds who did not
participate in organised sports outside of school hours were almost twice as
likely to be obese (OR = 1.9, 95% CI: 1.2-2.9). When stratified by ethnicity,
participation in sports was not related to lower obesity status in children of SE
Asian origin. One reason for this could be because SE Asian had very limited
participation in sports compared to their counterparts. Accordingly, we believe
that health promotion messages to avoid obesity need to be targeted ethnic
specifically.:
PMID- 24351776
TI - Are general practitioners ready and willing to tackle obesity management?
AB - SUMMARY: OBJECTIVE: To investigate general practitioners' (GPs') knowledge, role
perception, confidence and practices of managing adult and childhood overweight
and obesity, and to explore the association with GPs' attendance at Continuing
Professional Development (CPD) on overweight and obesity. METHODS: In 2007, all
GPs in seven Divisions of general practice in New South Wales were sent a
questionnaire on GPs perceptions and practices of weight counselling. RESULTS:
646 GPs participated (40% response rate). About half of the GPs (47%) believed
that only a small percentage of adults could reduce weight and maintain that
loss, whereas 33% had a similar belief in relation to children. Most GPs believed
that it was their role to manage weight and felt confident to do so with adults,
but fewer GPs felt confident in managing children. Nevertheless, just over one
third of GPs reported they counselled more than 10 adult patients, and a similar
proportion counselled more than 3 children per week. GPs who felt more confident
were more likely to counsel adults (OR = 2.69, p = 0.001) and children (OR =
3.31, p < 0.001). Those who received CPD were more likely to feel confident in
managing adults (OR = 1.56, p = 0.031) and children (OR = 2.19, p < 0.001).
CONCLUSIONS: Although the majority of GPs believe that weight management is their
role, only a small proportion regularly provided counselling. This may partly be
the result of GPs confidence in managing patients, especially children. CPD on
overweight and obesity may benefit GP confidence, but additional training is
needed to improve GP's counselling behaviour, particularly for children.
PMID- 24351777
TI - Adverse effects of obesity on beta-cell function in Japanese subjects with normal
glucose tolerance.
AB - SUMMARY: The purpose of the present study was to elucidate the role of obesity in
both early- and late-phase insulin secretion during an oral glucose tolerance
test (OGTT) performed with 75 g glucose in Japanese subjects. This was performed
using indices of beta-cell function adjusted for insulin sensitivity. Of 155
subjects assessed, 68 had normal glucose tolerance (NGT) and 87 had impaired
glucose tolerance (IGT). We used the homeostasis model assessment-insulin
resistance (HOMA-IR) index as an indicator of insulin sensitivity. As indicators
of beta-cell function, we used the HOMA-beta index, an insulinogenic index
(DeltaI30/DeltaG30), and DeltaAUC I/G(0-120), which were obtained in the OGTT. We
then reevaluated the results after adjusting the beta-cell function for insulin
sensitivity ([DeltaI30/DeltaG30]/HOMA-IR index and [DeltaAUC I/G(0-120)]/HOMA-IR
index). beta-Cell function was observed to reduce as the glucose tolerance
deteriorated from NGT to IGT. However, when the effects of obesity were
considered, the obese subjects with NGT already showed a decline in the (DeltaAUC
I/G(0-120))/HOMA-IR index value when compared with the nonobese subjects with
NGT, despite the fact these subjects did not differ with regard to
(DeltaI30/DeltaG30)/HOMA-IR index. As the glucose tolerance deteriorated to IGT,
both (DeltaI30/DeltaG30)/HOMA-IR index and (DeltaAUC I/G(0-120))/HOMA-IR index
decreased to an identical extent in both subgroups. These data indicate that
obesity causes a decrease in insulin secretion, especially during the late phase
following a glucose load, even if the glucose tolerance remains normal.:
PMID- 24351778
TI - Are baby boomers booming too much?
AB - SUMMARY: OBJECTIVE: To provide a social, demographic, and health-related
description of overweight and obese baby boomers (born between 1946 and 1964).
METHOD: Data were collected using a monthly chronic disease and risk factor
surveillance system in which a representative random sample of South Australians
are selected from the Electronic White Pages each month and interviewed using
computer assisted telephone interviewing (CATI). RESULTS: In 2006-2007, 65% of
baby boomers in South Australia were overweight or obese, and 26% were obese.
There were statistically significant increases in both categories between 2002
and 2007. In 2006-2007, the overweight or obese groups were significantly
different on a wide range of social, demographic and health-related variables
when compared to their non-overweight peers at the univariate level. In the
multivariate analysis the obese group was more likely to have risk factors (high
blood pressure, insufficient exercise) and chronic disease (diabetes, asthma,
arthritis). They were also more likely to be in lower socio-economic areas, to be
of Aboriginal or Torres Strait Islander origin and have lower levels of
education. CONCLUSIONS: Addressing the high rates of overweight and obesity
within the baby boomers generation should be a policy priority. As this
generation moves towards old age the significant associations between body mass
index and chronic disease and disability promise to increase demand upon an
already pressurized health system.
PMID- 24351779
TI - Comparison of waist circumference, body mass index, percent body fat and other
measure of adiposity in identifying cardiovascular disease risks among Thai
adults.
AB - SUMMARY: OBJECTIVE: To compare the abilities of body mass index (BMI), percent
body fat (%BF), waist circumference (WC), waist-hip ratio (WHR) and waist-height
ratio (WHtR) to identify cardiovascular disease risk factors. METHODS: This cross
sectional study is comprised of 1391 Thai participants (451 men and 940 women)
receiving annual health check-ups. Spearman's rank correlation was used to
determine the association of the five anthropometric indices with metabolic
parameters including fasting plasma glucose, triglyceride, high-density
lipoprotein and blood pressure. The prevalence of cardiovascular disease risk
factors was determined according to tertile of each anthropometric measure.
Receiver operating characteristic (ROC) curves were plotted to compare
anthropometric measure as predictors of the prevalence of cardiovascular risk
factors. RESULTS: Metabolic parameters were more strongly associated with %BF and
WHR and least correlated with BMI in men. Among women, BMI was most strongly
correlated with metabolic parameters. In both genders, the prevalence of
cardiovascular disease risk factors increased across successive tertiles for each
anthropometric measure. Review of ROC curves indicated that %BF and WHR performed
slightly better than other measures in identifying differences in CVD risk
factors among men. BMI performed at least as well or better than other measures
of adiposity among women. CONCLUSIONS: These findings confirm high correlations
between anthropometric measures and metabolic parameters. BMI, WC and other
measures were not materially different in identifying cardiovascular disease risk
factors. Although small differences were observed, the magnitudes of those
differences are not likely to be of public health or clinical significance.
PMID- 24351781
TI - A Tribute to Professor Maurice Tubiana.
PMID- 24351780
TI - Off-Target Effects of BCR-ABL and JAK2 Inhibitors.
AB - The advent of targeted oncolytic agents has created a revolution in the treatment
of malignancies. Perhaps best exemplified in myeloproliferative neoplasms (MPN),
the tyrosine kinase inhibitors, including inhibitors of BCR-ABL tyrosine kinase
and JAK2, have dramatically changed outcomes in persons with MPN. However,
clinically relevant dosing of these adenosine triphosphate-mimetic agents in
humans leads to inhibition of numerous tyrosine kinases beyond those touted by
drug manufacturers and studied in landmark clinical trials. These so-called off
target effects have been linked to both clinical efficacy and toxicity. Rational
drug development and serendipitous discovery of drug molecules allows the
clinician to select targeted oncolytic agents to treat a specific clinical
diagnosis and/or avoid exacerbation of concomitant disease states due to effects
upon signaling pathways. Understanding the off-target binding and effects upon
signaling pathway of the agents approved for the treatment of MPN will empower
the clinician to adroitly select pharmacotherapy, predict toxicities, and utilize
these agents in clinical practice for indications beyond MPN.
PMID- 24351783
TI - A review of the impact of preoperative chemoradiotherapy on outcome and
postoperative complications in esophageal cancer patients.
AB - Preoperative chemoradiotherapy has emerged in the treatment of esophageal cancer
as a means to down-stage tumors, improve local control, and possibly improve
overall survival. However, there are concerns that postoperative complications
may be increased by preoperative chemoradiotherapy. We review the rationale for
preoperative chemoradiotherapy. We review the literature to identify the
potential postoperative complications, the risk of complications, and the risk
factors for complications. Although individual and previous studies have shown an
increased risk of postoperative complications, the 4 most recent randomized
trials published after the year 2000 have not shown an increase in postoperative
complications and mortality rates in patients treated with preoperative
chemoradiation compared with patients treated with surgery alone. Pulmonary
complications are frequently reported, and we focus on dosimetric factors that
can be used to minimize lung toxicity. Several dose-volume-histogram parameters,
including V10>=40%, V15>=30%, V20>=20%, have been shown to correlate with 32% to
35% of pulmonary complications including pneumonia and acute respiratory distress
syndrome. More recent evidence has suggested that an absolute volume of lung
spared doses of > 5 Gy (VS5) correlates with pulmonary complications. As these
data show, low-dose volume may be more important in the prevention of pulmonary
complications than high-dose volume. These dosimetric constraints can be used by
physicians to prevent postoperative pulmonary complications in patients treated
with preoperative chemoradiotherapy.
PMID- 24351782
TI - Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better
Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer.
AB - OBJECTIVES: At diagnosis, 30% of patients with pancreatic cancer are unresectable
stage 3 locally advanced. The standard treatment for locally advanced pancreatic
cancer (LAPC) is not defined. The current study was conducted to assess the roles
of chemotherapy and chemoradiation for LAPC treatment. MATERIALS AND METHODS:
Between June 2006 and March 2011, 100 patients with LAPC were treated at the
Johns Hopkins Hospital. Retrospective analysis was performed to compare
cumulative incidence of progression (CIP) and overall survival (OS) among
different subgroups. RESULTS: For the 100 patients, the median OS was 15.8 months
and the median CIP was 8.4 months. The combination of chemotherapy and
chemoradiation before disease progression was significantly associated with
improved CIP (P=0.001) and improved OS when compared with chemoradiation alone
(median OS: 16.4 vs. 11.1 mo, P=0.03). Among patients receiving combination
treatment, patients who received chemotherapy first followed by chemoradiation
had a trend toward lower CIP (P=0.09) and improved OS (median OS: 18.1 vs. 11.0
mo, P=0.09). Patients who received >2 cycles of chemotherapy before
chemoradiation had a significantly decreased CIP (P=0.008) and a trend toward
better OS (median OS: 19.4 vs. 15.7 mo, P=0.10). On multivariate analysis,
receiving >2 cycles of chemotherapy before chemoradiation was associated with
improved CIP. CONCLUSIONS: Although combination chemotherapy and chemoradiation
is favored in the treatment of LAPC, longer induction chemotherapy may play a
more important role in sensitization of tumors to subsequent chemoradiation. Our
results support treating patients with induction chemotherapy for at least 3
cycles followed by consolidative chemoradiation. These results merit further
validation by a prospective study.
PMID- 24351784
TI - Smoking and pregnancy--a review on the first major environmental risk factor of
the unborn.
AB - Smoking cigarettes throughout pregnancy is one of the single most important
avoidable causes of adverse pregnancy outcomes and it represents the first major
environmental risk of the unborn. If compared with other risk factors in the
perinatal period, exposure to tobacco smoke is considered to be amongst the most
harmful and it is associated with high rates of long and short term morbidity and
mortality for mother and child. A variety of adverse pregnancy outcomes are
linked with cigarette consumption before and during pregnancy. Maternal prenatal
cigarette smoke disturbs the equilibrium among the oxidant and antioxidant
system, has negative impact on the genetic and cellular level of both mother and
fetus and causes a large quantity of diseases in the unborn child. These smoking
induced damages for the unborn offspring manifest themselves at various times in
life and for most only a very limited range of causal treatment exists.
Education, support and assistance are of high importance to decrease maternal and
fetal morbidity and mortality, as there are few other avoidable factors which
influence a child's health that profoundly throughout its life. It is imperative
that smoking control should be seen as a public health priority.
PMID- 24351785
TI - Occupational injuries on thoroughbred horse farms: a description of Latino and
non-Latino workers' experiences.
AB - Animal production is a dangerous industry and increasingly reliant on a Latino
workforce. Within animal production, little is known about the risks or the
occupational hazards of working on farms involved in various aspects of
thoroughbred horse breeding. Extant research suggests that horse workers are at
risk of musculoskeletal and respiratory symptoms, kicks, and other injuries.
However, limited known research has examined the experiences of the industry's
workers, including immigrant workers, despite their prominence and increased
vulnerability. Using data collected from thoroughbred farm representatives via a
phone-administered survey, a 2-hour face-to-face semi-structured interview, and
farm injury logs, this article identifies and describes types of injuries
experienced by workers (N = 284) and their surrounding circumstances. Results
indicate that general injuries and musculoskeletal strains, sprains, and tears
account for a majority of injuries among workers on thoroughbred farms. Upper
limbs and extremities are most frequently injured, while direct contact with the
horse accounted for over half of all injuries. No differences in the diagnoses or
distribution of injury were found by ethnicity; however, Latinos were more often
struck by or trampled by a horse while non-Latinos were more often injured by an
insect or plant. Implications and opportunities for future research are
discussed.
PMID- 24351786
TI - Social network characteristics and daily smoking among young adults in Sweden.
AB - A large number of studies have shown that friends' smoking behavior is strongly
associated with an individual's own risk for smoking. However, few studies have
examined whether other features of social networks, independently or conjointly
with friends' smoking behavior, may influence the risk for smoking. Because it is
characterized by the growing importance of friendship networks, the transition
from adolescence to young adulthood may constitute a particularly relevant period
on which to focus our investigation of network influences on smoking behavior.
The aim of this study was therefore to examine the consequences of peer smoking
as well as other network characteristics (friends' other health behaviors,
relationship content, and structural aspects of the network) on the risk for
smoking among young adults. The data was based on a cross-sectional survey of
Swedish 19-year-olds carried out in 2009 (n = 5,695) with a response rate of
51.6%. Logistic regression was the primary method of analysis. The results show
that having a large percentage of smokers in one's network was by far the most
important risk factor for daily smoking. The risk of daily smoking was 21.20 (CI
14.24. 31.54) if 76%-100% of the network members smoked. Having a high percentage
of physically active friends was inversely associated with daily smoking. The
risk of smoking was 0.65 (CI 0.42. 1.00) if 76%-100% of the network members were
physically active. No main associations between the other network characteristics
(relationship content and structural aspects of the network) and smoking were
found. However, there was an interaction between the percentage of smokers in the
network and relationship content (i.e., trust, relationship quality and
propensity to discuss problems): positive relationship content in combination
with peer smoking may increase the risk of smoking. Women with a high percentage
of smokers in their networks were also at higher risk of daily smoking than were
men with many smoking friends. Hence, it is important to consider the interplay
between peer smoking and other network characteristics on the risk of smoking,
where features of networks which traditionally are seen as constructive may
occasionally provide the impetus to smoke. Future studies should use longitudinal
data to study whether these findings reflect peer selection or peer influence.
PMID- 24351787
TI - The evolutionary puzzle of suicide.
AB - Mechanisms of self-destruction are difficult to reconcile with evolution's first
rule of thumb: survive and reproduce. However, evolutionary success ultimately
depends on inclusive fitness. The altruistic suicide hypothesis posits that the
presence of low reproductive potential and burdensomeness toward kin can increase
the inclusive fitness payoff of self-removal. The bargaining hypothesis assumes
that suicide attempts could function as an honest signal of need. The payoff may
be positive if the suicidal person has a low reproductive potential. The parasite
manipulation hypothesis is founded on the rodent-Toxoplasma gondii host-parasite
model, in which the parasite induces a "suicidal" feline attraction that allows
the parasite to complete its life cycle. Interestingly, latent infection by T.
gondii has been shown to cause behavioral alterations in humans, including
increased suicide attempts. Finally, we discuss how suicide risk factors can be
understood as nonadaptive byproducts of evolved mechanisms that malfunction.
Although most of the mechanisms proposed in this article are largely speculative,
the hypotheses that we raise accept self-destructive behavior within the
framework of evolutionary theory.
PMID- 24351788
TI - Design and experimental approach to the construction of a human signal-molecule
profiling database.
AB - The human signal-molecule-profiling database (HSMPD) is designed as a prospective
medical database for translational bioinformatics (TBI). To explore the
feasibility of low-cost database construction, we studied the roadmap of HSMPD. A
HSMPD-oriented tool, called "signal-molecule-profiling (SMP) chip" was developed
for data acquisition, which can be employed in the routine blood tests in
hospitals; the results will be stored in the HSMPD system automatically. HSMPD
system can provide data services for the TBI community, which generates a stable
income to support the data acquisition. The small-scale experimental test was
performed in the hospital to verify SMP chips and the demo HSMPD software. One
hundred and eighty nine complete SMP records were collected, and the demo HSMPD
system was also evaluated in the survey study on patients and doctors. The
function of SMP chip was verified, whereas the demo HSMPD software needed to be
improved. The survey study showed that patients would only accept free tests of
SMP chips when they originally needed blood examinations. The study indicated
that the construction of HSMPD relies on the self-motivated cooperation of the
TBI community and the traditional healthcare system. The proposed roadmap
potentially provides an executable solution to build the HSMPD without high
costs.
PMID- 24351789
TI - Healthcare professional perspectives on quality and safety in New Zealand public
hospitals: findings from a national survey.
AB - BACKGROUND: Few studies have sought to measure health professional perceptions of
quality and safety across an entire system of public hospitals. Therefore, three
questions that gauge different aspects of quality and safety were included in a
national New Zealand survey of clinical governance. METHODS: Three previously
used questions were adapted. A total of 41040 registered health professionals
employed in District Health Boards were invited to participate in an online
survey. Analyses were performed using the R statistical environment. Proportional
odds mixed models were used to quantify associations between demographic
variables and responses on five-point scales. Relationships between other
questions in the survey and the three quality and safety questions were
quantified with the Pearson correlation coefficient. RESULTS: A 25% response rate
delivered 10303 surveys. Fifty-seven percent of respondents (95% CI: 56-58%)
agreed that health professionals in their District Health Board worked together
as a team; 70% respondents (95% CI: 69-70%) agreed that health professionals
involved patients and families in efforts to improve patient care; and 69% (95%
CI: 68-70%) agreed that it was easy to speak up in their clinical area if they
perceived a problem with patient care. Correlations showed links between
perceptions of stronger clinical leadership and performances on the three
questions, as well as with other survey items. The proportional mixed model also
revealed response differences by respondent characteristics. CONCLUSIONS: The
findings suggest positive commitment to quality and safety among New Zealand
health professionals and their employers, albeit with variations by district,
profession, gender and age, but also scope for improvement. The study also
contributes to the literature indicating that clinical leadership is an important
contributor to quality improvement. WHAT IS KNOWN ABOUT THE TOPIC? Various
studies have explored aspects of healthcare quality and safety, generally within
a hospital or group of hospitals, using a lengthy tool such as the 'safety
climate survey'. WHAT DOES THIS PAPER ADD? We used a simple three-question survey
approach (derived from existing measures) to measuring healthcare professionals'
perceptions of quality and safety in New Zealand's public hospitals. In doing so,
we also collected the first such information on this. WHAT ARE THE IMPLICATIONS
FOR PRACTITIONERS? New Zealand policy makers and health professionals can take
some comfort in our findings, but also note that there is considerable scope for
improvement. Our finding that more positive perceptions of quality and safety
were related to perceptions of stronger clinical leadership adds to the
international literature indicating the importance of this. Policy makers and
hospital managers should support strong clinical leadership.
PMID- 24351790
TI - Vascular complications and coagulation-related changes in the perioperative
period in Japanese patients undergoing non-cardiac surgery.
AB - AIM: To properly assess the guidance for perioperative management, we undertook a
clinical epidemiology study with the primary aim of evaluating the incidence of
perioperative vascular complications and their associated factors in a cohort of
Japanese patients who underwent non-cardiac surgery in a tertiary medical care
center. METHODS: This observational study comprised two parts. In the first part,
thrombotic and bleeding events and their risk factors in the perioperative period
were evaluated in a total of 2,654 consecutive patients. In the second part,
perioperative changes in coagulation-related factors, including the thrombin
antithrombin complex(TAT) and platelet aggregation activity, were serially
characterized in 82 individuals randomly chosen from the consecutive patients.
RESULTS: The incidence of perioperative vascular complications was as follows:
1.0% for major bleeding, 0.21% for stroke and 0.21% for venous thromboembolism.
No episodes of symptomatic myocardial infarction were identified in the studied
population. Perioperative changes in coagulation-related factors were found to be
complex and correlated in the mixed direction of pro- and anticoagulation. The
TAT values showed prolonged(across postoperative days 1-5) and prominent(>116%
increase) perioperative activation of coagulation, whereas global coagulation
parameters, such as the prothrombin time, showed a tendency of anticoagulation in
the immediate postoperative period. CONCLUSIONS: Our data confirm the relatively
low incidence of perioperative vascular complications in the general Japanese non
cardiac surgical population. Given the delicate balance between thrombotic and
bleeding events, it is important to comprehensively understand the associations
between the patient's baseline risk factors and vascular complications for
effective clinical management.
PMID- 24351792
TI - Computation of mean and variance of the radiotherapy dose for PCA-modeled random
shape and position variations of the target.
AB - Radiotherapy dose delivery in the tumor and surrounding healthy tissues is
affected by movements and deformations of the corresponding organs between
fractions. The random variations may be characterized by non-rigid, anisotropic
principal component analysis (PCA) modes. In this article new dynamic dose
deposition matrices, based on established PCA modes, are introduced as a tool to
evaluate the mean and the variance of the dose at each target point resulting
from any given set of fluence profiles. The method is tested for a simple cubic
geometry and for a prostate case. The movements spread out the distributions of
the mean dose and cause the variance of the dose to be highest near the edges of
the beams. The non-rigidity and anisotropy of the movements are reflected in both
quantities. The dynamic dose deposition matrices facilitate the inclusion of the
mean and the variance of the dose in the existing fluence-profile optimizer for
radiotherapy planning, to ensure robust plans with respect to the movements.
PMID- 24351791
TI - Patterns of recurrence of postpartum hemorrhage in a large population-based
cohort.
AB - OBJECTIVE: Although a history of postpartum hemorrhage (PPH) is a recognized risk
factor for PPH in subsequent pregnancies, little is known about how the risk
accumulates over multiple pregnancies, how recurrence varies by PPH subtype, and
whether recurrence can be explained by chronic maternal conditions. STUDY DESIGN:
Risks of PPH were assessed according to a history of PPH, severity, and subtype
(atony, retained placenta, or lacerations) in 538,332 primiparous women whose
data were included in the Swedish Medical Birth Register from 1997-2009. The role
of stable maternal risk factors was evaluated in regression models that predicted
probability of recurrent PPH in second and third pregnancy. RESULTS: Women with a
history of PPH had a 3-fold increased risk of PPH in their second pregnancy
compared with unaffected women (15.0% vs 5.0%, respectively). Adjustment for
stable maternal risk factors did not attenuate this risk significantly (adjusted
relative risk, 3.0; 95% confidence interval, 2.9-3.1). In a third pregnancy, the
risk of PPH was 26.6% after 2 previously affected pregnancies, compared with 4.4%
in women with no previous PPH. A history of a specific type of PPH predicted
recurrence of PPH in the second pregnancy, not only of the same type but other
causes as well. CONCLUSION: PPH risk is highest among women with >1 previously
affected delivery and in those with a previous severe PPH. Chronic conditions
that are known to be risk factors for PPH do not explain the recurrence risks.
The recurrence patterns across PPH subtypes may point to shared pathologic
mechanisms underlying the varying PPH causes.
PMID- 24351793
TI - Effects of rapeseed and soybean oil dietary supplementation on bovine fat
metabolism, fatty acid composition and cholesterol levels in milk.
AB - The main goal of this experiment was to study the effect of milk fat depression,
induced by supplementing diet with plant oils, on the bovine fat metabolism, with
special interest in cholesterol levels. For this purpose 39 cows were divided in
three groups and fed different rations: a control group (C) without any oil
supplementation and two groups with soybean oil (SO) or rapeseed oil (RO) added
to the partial mixed ration (PMR). A decrease in milk fat percentage was observed
in both oil feedings with a higher decrease of -1.14 % with SO than RO with -0.98
% compared with the physiological (-0.15 %) decline in the C group. There was no
significant change in protein and lactose yield. The daily milk cholesterol yield
was lower in both oil rations than in control ration, while the blood cholesterol
level showed an opposite variation. The milk fatty acid pattern showed a highly
significant decrease of over 10 % in the amount of saturated fatty acids (SFA) in
both oil feedings and a highly significant increase in mono (MUFA) and poly
(PUFA) unsaturated fatty acids, conjugated linoleic acids (CLA) included. The
results of this experiment suggest that the feeding of oil supplements has a high
impact on milk fat composition and its significance for human health, by
decreasing fats with a potentially negative effect (SFA and cholesterol) while
simultaneously increasing others with positive (MUFA, PUFA, CLA).
PMID- 24351795
TI - Preclinical and clinical development of a YFV 17 D-based chimeric vaccine against
West Nile virus.
AB - Substantial success has been achieved in the development and implementation of
West Nile (WN) vaccines for horses; however, no human WN vaccines are approved.
This review focuses on the construction, pre-clinical and clinical
characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed
of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are
replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies
demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF
17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing
antibody titers after inoculation in hamsters and monkeys and protected immunized
animals from lethal challenge including intracerebral inoculation of high dose of
WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were
assessed in one phase I study and in two phase II clinical trials. No safety
signals were detected in the three clinical trials with no remarkable differences
in incidence of adverse events (AEs) between vaccine and placebo recipients.
Viremia was transient and the mean viremia levels were low. The vaccine elicited
strong and durable neutralizing antibody and cytotoxic T cell responses. WN
epidemiology impedes a classical licensure pathway; therefore, innovative
licensure strategies should be explored.
PMID- 24351794
TI - Vector-virus interactions and transmission dynamics of West Nile virus.
AB - West Nile virus (WNV; Flavivirus; Flaviviridae) is the cause of the most
widespread arthropod-borne viral disease in the world and the largest outbreak of
neuroinvasive disease ever observed. Mosquito-borne outbreaks are influenced by
intrinsic (e.g., vector and viral genetics, vector and host competence, vector
life-history traits) and extrinsic (e.g., temperature, rainfall, human land use)
factors that affect virus activity and mosquito biology in complex ways. The
concept of vectorial capacity integrates these factors to address interactions of
the virus with the arthropod host, leading to a clearer understanding of their
complex interrelationships, how they affect transmission of vector-borne disease,
and how they impact human health. Vertebrate factors including host competence,
population dynamics, and immune status also affect transmission dynamics. The
complexity of these interactions are further exacerbated by the fact that not
only can divergent hosts differentially alter the virus, but the virus also can
affect both vertebrate and invertebrate hosts in ways that significantly alter
patterns of virus transmission. This chapter concentrates on selected components
of the virus-vector-vertebrate interrelationship, focusing specifically on how
interactions between vector, virus, and environment shape the patterns and
intensity of WNV transmission.
PMID- 24351796
TI - Gene therapy strategies for HIV/AIDS: preclinical modeling in humanized mice.
AB - In the absence of an effective vaccine and lack of a complete cure, gene therapy
approaches to control HIV infection offer feasible alternatives. Due to the
chronic nature of infection, a wide window of opportunity exists to gene modify
the HIV susceptible cells that continuously arise from the bone marrow source. To
evaluate promising gene therapy approaches that employ various anti-HIV
therapeutic molecules, an ideal animal model is necessary to generate important
efficacy and preclinical data. In this regard, the humanized mouse models that
harbor human hematopoietic cells susceptible to HIV infection provide a suitable
in vivo system. This review summarizes the currently used humanized mouse models
and different anti-HIV molecules utilized for conferring HIV resistance.
Humanized mouse models are compared for their utility in this context and provide
perspectives for new directions.
PMID- 24351798
TI - The p36 isoform of murine cytomegalovirus m152 protein suffices for mediating
innate and adaptive immune evasion.
AB - The MHC-class I (MHC-I)-like viral (MHC-Iv) m152 gene product of murine
cytomegalovirus (mCMV) was the first immune evasion molecule described for a
member of the beta-subfamily of herpesviruses as a paradigm for analogous
functions of human cytomegalovirus proteins. Notably, by interacting with
classical MHC-I molecules and with MHC-I-like RAE1 family ligands of the
activatory natural killer (NK) cell receptor NKG2D, it inhibits presentation of
antigenic peptides to CD8 T cells and the NKG2D-dependent activation of NK cells,
respectively, thus simultaneously interfering with adaptive and innate immune
recognition of infected cells. Although the m152 gene product exists in
differentially glycosylated isoforms whose individual contributions to immune
evasion are unknown, it has entered the scientific literature as m152/gp40, based
on the quantitatively most prominent isoform but with no functional
justification. By construction of a recombinant mCMV in which all three N
glycosylation sites are mutated (N61Q, N208Q, and N241Q), we show here that N
linked glycosylation is not essential for functional interaction of the m152
immune evasion protein with either MHC-I or RAE1. These data add an important
functional detail to recent structural analysis of the m152/RAE1g complex that
has revealed N-glycosylations at positions Asn61 and Asn208 of m152 distant from
the m152/RAE1g interface.
PMID- 24351797
TI - The role of innate immunity in conditioning mosquito susceptibility to West Nile
virus.
AB - Arthropod-borne viruses (arboviruses) represent an emerging threat to human and
livestock health globally. In particular, those transmitted by mosquitoes present
the greatest challenges to disease control efforts. An understanding of the
molecular basis for mosquito innate immunity to arbovirus infection is therefore
critical to investigations regarding arbovirus evolution, virus-vector ecology,
and mosquito vector competence. In this review, we discuss the current state of
understanding regarding mosquito innate immunity to West Nile virus. We draw from
the literature with respect to other virus-vector pairings to attempt to draw
inferences to gaps in our knowledge about West Nile virus and relevant vectors.
PMID- 24351799
TI - Make yourself at home: viral hijacking of the PI3K/Akt signaling pathway.
AB - As viruses do not possess genes encoding for proteins required for translation,
energy metabolism or membrane biosynthesis, they are classified as obligatory
intracellular parasites that depend on a host cell to replicate. This genome
limitation forces them to gain control over cellular processes to ensure their
successful propagation. A diverse spectrum of virally encoded proteins tackling a
broad spectrum of cellular pathways during most steps of the viral life cycle
ranging from the host cell entry to viral protein translation has evolved. Since
the host cell PI3K/Akt signaling pathway plays a critical regulatory role in many
cellular processes including RNA processing, translation, autophagy and
apoptosis, many viruses, in widely varying ways, target it. This review focuses
on a number of remarkable examples of viral strategies, which exploit the
PI3K/Akt signaling pathway for effective viral replication.
PMID- 24351800
TI - The cyclin-dependent kinase ortholog pUL97 of human cytomegalovirus interacts
with cyclins.
AB - The human cytomegalovirus (HCMV)-encoded protein kinase, pUL97, is considered a
cyclin-dependent kinase (CDK) ortholog, due to shared structural and functional
characteristics. The primary mechanism of CDK activation is binding to
corresponding cyclins, including cyclin T1, which is the usual regulatory
cofactor of CDK9. This study provides evidence of direct interaction between
pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses.
Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin
T1 in subnuclear compartments, most pronounced in viral replication centres. The
distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and
host cell type. The sequence domain of pUL97 responsible for the interaction with
cyclin T1 was between amino acids 231-280. Additional co-immunoprecipitation
analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners.
Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay
strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a
substrate concentration-dependent manner. This is the first demonstration of
interaction between a herpesviral CDK ortholog and cellular cyclins.
PMID- 24351801
TI - Clinical Diagnosis, Viral PCR, and Antibiotic Utilization in Community-Acquired
Pneumonia.
AB - We evaluated the intensity of antibiotic therapy in patients in whom the etiology
of community-acquired pneumonia (CAP) was determined using newly available
diagnostic techniques. For 1 year, we studied all patients admitted for findings
consistent with CAP. Sputum and blood cultures, urinary pneumococcal and
Legionella antigens, and viral polymerase chain reaction (PCR) were studied
prospectively. Patients were stratified based on the final diagnoses: proven
bacterial, presumptive bacterial, viral, fungal, undetermined, and uninfected. We
determined the number of antibiotics given, duration of antibiotic therapy, and
intensity of antibiotic use determined by antibiotic-days defined as the sum, in
each patient, of all antibiotics given for CAP and the number of days given.
Median duration and intensity of antibiotics were 12 and 18 days for proven, and
13 and 16.5 days for presumed bacterial CAP (P > 0.9). When positive viral PCR
results were not disclosed to primary care physicians, antibiotic use was similar
to that in bacterial CAP. However, in 11 cases, when positive viral PCR results
were disclosed, duration and intensity of antibiotic use were reduced to 7 and 9
days, respectively (P = 0.05 and 0.08, respectively). Antibiotic use was similar
in patients with bacterial pneumonia and those judged on clinical grounds to have
likely nonbacterial infection. Despite obvious differences in clinical syndromes
and final diagnoses, the intensity of antibiotic therapy was similar in all
groups of patients admitted for CAP with the exception of those who were
uninfected and whose primary care physicians were informed of a positive viral
PCR.
PMID- 24351802
TI - Association of cognitive dysfunction with cardiovascular disease events in
elderly hypertensive patients.
AB - OBJECTIVES: This study assesses whether presence of cognitive dysfunction can be
a marker associated with the development of cardiovascular disease (CVD) events
independent of ambulatory blood pressure (BP) or other indices of target organ
damage (TOD) in elderly hypertensive patients. METHODS: We recruited 585
hypertensive patients (mean age, 73 years; 41% men) who were ambulatory, lived
independently, and were without clinically overt dementia. Cognitive function was
assessed by Mini-Mental State Examination (MMSE) at baseline, and CVD events
(coronary artery disease, stroke, congestive heart failure, and sudden death)
were prospectively ascertained. Cognitive dysfunction was defined as the lowest
quartile of MMSE scores (n = 183, median 24 points). RESULTS: CVD events occurred
in 42 people over an average of 2.8 years (1644 person-years). The prevalence of
cognitive dysfunction was higher in patients with CVD events than those without
(57 vs. 29%; both P <0.001) at baseline. Cognitive dysfunction was associated
with CVD events, after adjustment for nocturnal SBP and evidence of TOD [i.e.
albuminuria, cardiac hypertrophy, and carotid-artery intima-media thickness
(IMT)], hazard ratio 2.5-2.9 (all P <0.01). Incorporation of MMSE in the risk
model (including age, estimated glomerular filtration rate, and preexisting CVD)
improved the C-statistics (from 0.691 to 0.741) and resulted in a net
reclassification improvement of 17.6% (P = 0.02). In contrast, incorporation of
albuminuria, cardiac hypertrophy, and high carotid-artery IMT added little
further improvement in the risk prediction. CONCLUSION: Cognitive dysfunction is
an independent marker associated with increased risk of CVD events in elderly
hypertensive patients.
PMID- 24351803
TI - Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at
increased cardiovascular risk.
AB - RATIONALE: We hypothesized increasing obstructive sleep apnea (OSA) severity
would be associated with nondipping blood pressure (BP) in increased
cardiovascular disease (CVD) risk. METHODS: Baseline data from 298 cardiology
patients recruited for a multicenter randomized controlled trial were examined.
Dipping was defined as a sleep-related BP or heart rate (HR) reduction of at
least 10%. Logistic regression models were fit, adjusting for age, sex, race,
BMI, CVD risk factors, CVD, and study site. RESULTS: There was a statistically
significant 4% increase in the odds of nondipping SBP per 1-unit increase in both
apnea hypopnea index (AHI) and oxygen desaturation index (ODI). There was no
significant relationship between AHI and nondipping mean arterial pressure (MAP);
however, a 3% increase in the odds of nondipping MAP per 1-unit increase in ODI
was observed [odds ratio (OR) = 1.03; 95% confidence interval (CI) 1.00-1.05]. At
severe OSA levels, a 10 and 4% increase in odds of nondipping DBP per 1-unit
increase in AHI and ODI were observed, respectively. A 6% [OR = 1.06; 95% CI
(1.01-1.10)] increase in nondipping HR odds was observed with each increase in
ODI until the upper quartile of ODI. CONCLUSION: In patients at cardiovascular
risk and moderate-to-severe OSA, increasing AHI and/or ODI were associated with
increased odds of nondipping SBP and nondipping MAP. More severe levels of AHI
and ODI also were associated with nondipping DBP. These results support
progressive BP burden associated with increased OSA severity even in patients
managed by cardiology specialty care.
PMID- 24351804
TI - Long-term intense resistance training in men is associated with preserved cardiac
structure/function, decreased aortic stiffness, and lower central augmentation
pressure.
AB - OBJECTIVE: There have been contradictory reports regarding resistance exercise
and central arterial compliance. The American Heart Association has recommended
its use in preventing/treating cardiovascular diseases. We examined the effects
of long-term endurance running and intense resistance training on central
hemodynamics, compared with healthy control (CON). METHODS: Sixty-nine male
participants, 25-50 years [19 intense resistance trained (IRT) group, 21
endurance runners, and 29 CON] were investigated by radial tonometry-pulse wave
analysis, pulse wave velocity (PWV), and echocardiogram. Data were expressed as
mean +/- SE (median). Differences were tested by analysis of variance and
analysis of covariance was used to adjust for confounding variables. RESULTS:
There were no differences among groups regarding age, height (Ht), brachial and
central blood pressure. Resting heart rate (HR) was lower and high-density
lipoprotein cholesterol (HDL-C) higher in endurance runners. Weight, peripheral
pulse pressure, and pulse pressure amplification were higher and HDL-C lower in
the IRT group. Left ventricular mass and creatine phosphokinase were higher in
trained participants. Relative wall thickness was similar among groups. The ratio
of the velocity of peak E and A waves (E/A) was higher and PWV significantly
lower in endurance runners (7.2 +/- 0.14 m/s) and IRT (7.5 +/- 0.14 m/s) as
compared with CON (8.2 +/- 0.16 m/s) even after adjustments for age, Ht, HR and
mean arterial pressure (MAP), or mean systolic pressure. Differences in central
augmentation pressure (cAP) adjusted for age, height, systolic or MAP, PWV, and
HR (IRT equal to 0.08 +/- 0.9, CON equal to 3.4 +/- 0.9 and endurance running
equal to 3.6 +/- 1) were no longer significant after further adjustments to
aortic diameter or weight. CONCLUSION: Long-term resistance training in men is
associated with preserved cardiac structure/function, decreased aortic stiffness,
and lower cAP.
PMID- 24351805
TI - C-reactive protein and fibrinogen levels as determinants of recurrent
preeclampsia: a prospective cohort study.
AB - OBJECTIVE: Women with a history of early-onset preeclampsia have an increased
risk of recurrent preeclampsia and are more prone to develop future
cardiovascular disease. At present, risk factors underlying this association are
not well characterized. We investigated whether the risk of recurrent
preeclampsia is associated with pre-pregnancy levels of common cardiovascular and
inflammatory markers. METHODS: Reproductive follow-up and cardiovascular
parameters were obtained for 150 primiparae with a history of early-onset
preeclampsia 6-12 months after their first delivery. Simultaneously, fasting
plasma samples were collected and tested for lipids, glucose, C-reactive protein
and fibrinogen. The relative contribution of each marker to the recurrence risk
of preeclampsia and preterm delivery was estimated by Cox proportional hazard
models. RESULTS: Forty-two women (28%) developed preeclampsia in a next
pregnancy. Recurrent preeclampsia was related to elevated pre-pregnancy levels of
C-reactive protein and fibrinogen when compared to women who did not develop
recurrent disease. We found no associations between recurrent preeclampsia and
maternal age, pre-pregnancy BMI, smoking or fasting levels of total cholesterol,
high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol,
triglycerides and glucose. CONCLUSION: These observations support a role for
inflammation in recurrent hypertensive disorders of pregnancy similar to its
contribution to later-life atherosclerosis and risk of cardiovascular disease.
PMID- 24351806
TI - Preparing a 21st century workforce: is it time to consider clinically based,
competency-based training of health practitioners?
AB - Health workforce training in the 21st century is still based largely on 20th
century healthcare paradigms that emphasise professionalisation at the expense of
patient-focussed care. This is illustrated by the paradox of increased training
times for health workers that have corresponded with workforce shortages, the
limited career options and pathways for paraprofessional workers, and inefficient
clinical training models that detract from, rather than add to, service capacity.
We propose instead that a 21st century health workforce training model should be:
situated in the clinical setting and supported by outsourced university training
(not the other way around); based on the achievement of specific milestones
rather than being time-defined; and incorporate para-professional career pathways
that allow trainees to 'step-off' with a useable qualification following the
achievement of specific competencies. Such a model could be facilitated by
existing technology and clinical training infrastructure, with enormous potential
for economies of scale in the provision of formal training. The benefits of a
clinically based, competency-based model include an increase in clinical service
capacity, and clinical training resources become a resource for the delivery of
healthcare, not just education. Existing training models are unsustainable, and
are not preparing a workforce with the flexibility the 21st century demands.
PMID- 24351807
TI - Dynamics of order reconstruction in a nanoconfined nematic liquid crystal with a
topological defect.
AB - At the wall in a hybrid nematic cell with strong anchoring, the nematic director
is parallel to one wall and perpendicular to the other. Within the Landau-de
Gennes theory, we have investigated the dynamics of s = +/-1/2 wedge
disclinations in such a cell, using the two-dimensional finite-difference
iterative method. Our results show that with the cell gap decreasing, the core of
the defect explodes, and the biaxiality propagates inside the cell. At a critical
value of dc* ~ 9xi (where xi is the characteristic length for order-parameter
changes), the exchange solution is stable, while the defect core solution becomes
metastable. Comparing to the case with no initial disclination, the value at
which the exchange solution becomes stable increases relatively. At a critical
separation of dc ~ 6xi, the system undergoes a structural transition, and the
defect core merges into a biaxial layer with large biaxiality. For weak anchoring
boundary conditions, a similar structural transition takes place at a relative
lower critical value. Because of the weakened frustration, the asymmetric
boundary conditions repel the defect to the weak anchoring boundary and have a
relatively lower critical value of da, where the shape of the defect deforms.
Further, the response time between two very close cell gaps is about tens of
microseconds, and the response becomes slower as the defect explodes.
PMID- 24351808
TI - EZH2 down-regulation exacerbates lipid accumulation and inflammation in in vitro
and in vivo NAFLD.
AB - Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent, chronic
liver diseases, worldwide. It is a multifactorial disease caused by complex
interactions between genetic, epigenetic and environmental factors. Recently,
several microRNAs, some of which epigenetically regulated, have been found to be
up- and/or down-regulated during NAFLD development. However, in NAFLD, the
essential role of the Polycomb Group protein Enhancer of Zeste Homolog 2 (EZH2),
which controls the epigenetic silencing of specific genes and/or microRNAs by
trimethylating Lys27 on histone H3, still remains unknown. In this study, we
demonstrate that the nuclear expression/activity of the EZH2 protein is down
regulated both in livers from NAFLD rats and in the free fatty acid-treated
HepG2. The drop in EZH2 is inversely correlated with: (i) lipid accumulation;
(ii) the expression of pro-inflammatory markers including TNF-alpha and TGF-beta;
and (iii) the expression of miR-200b and miR-155. Consistently, the
pharmacological inhibition of EZH2 by 3-Deazaneplanocin A (DZNep) significantly
reduces EZH2 expression/activity, while it increases lipid accumulation,
inflammatory molecules and microRNAs. In conclusion, the results of this study
suggest that the defective activity of EZH2 can enhance the NAFLD development by
favouring steatosis and the de-repression of the inflammatory genes and that of
specific microRNAs.
PMID- 24351809
TI - Genome-wide analysis of respiratory burst oxidase homologs in grape (Vitis
vinifera L.).
AB - Plant respiratory burst oxidase homolog (rboh) genes appear to play crucial roles
in plant development, defense reactions and hormone signaling. In this study, a
total of seven rboh genes from grape were identified and characterized. Genomic
structure and predicted protein sequence analysis indicated that the sequences of
plant rboh genes are highly conserved. Synteny analysis demonstrated that several
Vvrboh genes were found in corresponding syntenic blocks of Arabidopsis,
suggesting that these genes arose before the divergence of the respective
lineages. The expression pattern of Vvrboh genes in different tissues was
assessed by qRT-PCR and two were constitutively expressed in all tissues tested.
The expression profiles were similarly analyzed following exposure to various
stresses and hormone treatments. It was shown that the expression levels of
VvrbohA, VvrbohB and VvrbohC1 were significantly increased by salt and drought
treatments. VvrbohB, VvrbohC2, and VvrbohD exhibited a dramatic up-regulation
after powdery mildew (Uncinula necator (Schw.) Burr.) inoculation, while VvrbohH
was down-regulated. Finally, salicylic acid treatment strongly stimulated the
expression of VvrbohD and VvrbohH, while abscisic acid treatment induced the
expression of VvrbohB and VvrbohH. These results demonstrate that the expression
patterns of grape rboh genes exhibit diverse and complex stress-response
expression signatures.
PMID- 24351810
TI - The involvement of RhoA and Wnt-5a in the tumorigenesis and progression of
ovarian epithelial carcinoma.
AB - BACKGROUND: Ras homolog gene family member A (RhoA) is involved in Wnt-5a-induced
migration of gastric and breast cancer cells. We investigated the roles of RhoA
and Wnt-5a in ovarian carcinoma. METHODS: RhoA and Wnt-5a mRNA and protein
expression in normal fallopian tube epithelium, benign tumors, primary ovarian
carcinomas, and metastatic omentum were quantified. RhoA or Wnt-5a was knocked
down in OVCAR3 ovarian carcinoma cells using siRNAs and cell phenotype and
expression of relevant molecules were assayed. RESULTS: RhoA and Wnt-5a mRNA and
protein expression were found to be significantly higher in metastatic omentum
than in ovarian carcinomas, benign tumors, and normal fallopian tube epithelium
(p < 0.05), and positively associated with differentiation and FIGO staging
(stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). RhoA and Wnt-5a
expression were positively correlated in ovarian carcinoma (p = 0.001, R2 =
0.1669). RhoA or Wnt-5a knockdown downregulated RhoA and Wnt-5a expression;
reduced cell proliferation; promoted G1 arrest and apoptosis; suppressed
lamellipodia formation, cell migration, and invasion; and reduced PI3K, Akt,
p70S6k, Bcl-xL, survivin, and VEGF mRNA or protein expression. CONCLUSIONS: This
is the first demonstration that RhoA and Wnt-5a are associated with ovarian
carcinogenesis and apoptosis inhibition; there might be positive correlation
between RhoA and Wnt-5a expression. RhoA is a potential tumorigenesis,
differentiation, and progression biomarker in ovarian carcinoma.
PMID- 24351811
TI - Neuritogenic monoglyceride derived from the constituent of a marine fish for
activating the PI3K/ERK/CREB signalling pathways in PC12 cells.
AB - A neuritogenic monoglyceride, 1-O-(myristoyl) glycerol (MG), was isolated from
the head of Ilisha elongate using a PC12 cell bioassay system, and its chemical
structure was elucidated using spectroscopic methods. MG significantly induced
42% of the neurite outgrowth of PC12 cells at a concentration of 10 MUM. To study
the structure-activity relationships of MG, a series of monoglycerides was
designed and synthesised. Bioassay results indicated that the alkyl chain length
plays a key role in the neuritogenic activity of the monoglycerides. The groups
that link the propane-1,2-diol and alkyl chain were also investigated. An ester
linkage, rather than an amido one, was found to be optimal for neuritogenic
activity. Therefore, 1-O-(stearoyl) glycerol (SG), which induces 57% of the
neurite outgrowth of PC12 cells at 10 MUM, was determined to be a lead compound
for neuritogenic activity. We then investigated the mechanism of action of
neurite outgrowth induced by SG on PC12 cells using protein specific inhibitors
and Western blot analysis. The mitogen-activated kinase/ERK kinase (MEK)
inhibitor U0126 and the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002
significantly decreased neurite outgrowth. At the same time, SG increased
phosphorylation of CREB in protein level. Thus, SG-induced neuritogenic activity
depends on the activation of the extracellular-regulated protein kinase (ERK),
cAMP responsive element-binding protein (CREB) and PI3K signalling pathways in
PC12 cells.
PMID- 24351813
TI - CXCL10 decreases GP73 expression in hepatoma cells at the early stage of
hepatitis C virus (HCV) infection.
AB - Golgi protein 73 (GP73), which is up-regulated in hepatocellular carcinoma (HCC),
has recently been identified as a novel serum marker for HCC diagnosis. Several
reports also noted the increased levels of GP73 expression in chronic liver
disease in patients with acute hepatitis of various etiologies, chronic Hepatitis
C virus (HCV) infection and alcoholic liver disease. The molecular mechanisms of
GP73 expression in HCV related liver disease still need to be determined. In this
study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73
was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed
in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and
HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73
expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in
hepatocytes with cytopathic effect at advanced stage of HCV infection, and
further research is needed to determine the unknown factors affecting GP73
expression. In conclusion, our study provided additional evidence for the roles
of GP73 in liver disease.
PMID- 24351812
TI - Molecular cloning and expression of CYP9A61: a chlorpyrifos-ethyl and lambda
cyhalothrin-inducible cytochrome P450 cDNA from Cydia pomonella.
AB - Cytochrome P450 monooxygenases (CYPs or P450s) play paramount roles in
detoxification of insecticides in a number of insect pests. However, little is
known about the roles of P450s and their responses to insecticide exposure in the
codling moth Cydia pomonella (L.), an economically important fruit pest. Here we
report the characterization and expression analysis of the first P450 gene,
designated as CYP9A61, from this pest. The full-length cDNA sequence of CYP9A61
is 2071 bp long and its open reading frame (ORF) encodes 538 amino acids.
Sequence analysis shows that CYP9A61 shares 51%-60% identity with other known
CYP9s and contains the highly conserved substrate recognition site SRS1, SRS4 and
SRS5. Quantitative real-time PCR showed that CYP9A61 were 67-fold higher in the
fifth instar larvae than in the first instar, and more abundant in the silk gland
and fat body than other tissues. Exposure of the 3rd instar larvae to 12.5 mg L(
1) of chlorpyrifos-ethyl for 60 h and 0.19 mg L(-1) of lambda-cyhalothrin for 36
h resulted in 2.20- and 3.47-fold induction of CYP9A61, respectively. Exposure of
the 3rd instar larvae to these two insecticides also significantly enhanced the
total P450 activity. The results suggested that CYP9A61 is an insecticide
detoxifying P450.
PMID- 24351814
TI - Alteration of dynein function affects alpha-synuclein degradation via the
autophagosome-lysosome pathway.
AB - Growing evidence suggests that dynein dysfunction may be implicated in the
pathogenesis of neurodegeneration. It plays a central role in aggresome
formation, the delivery of autophagosome to lysosome for fusion and degradation,
which is a pro-survival mechanism essential for the bulk degradation of misfolded
proteins and damaged organells. Previous studies reported that dynein dysfuntion
was associated with aberrant aggregation of alpha-synuclein, which is a major
component of inclusion bodies in Parkinson's disease (PD). However, it remains
unclear what roles dynein plays in alpha-synuclein degradation. Our study
demonstrated a decrease of dynein expression in neurotoxin-induced PD models in
vitro and in vivo, accompanied by an increase of alpha-synuclein protein level.
Dynein down-regulation induced by siRNA resulted in a prolonged half-life of
alpha-synuclein and its over-accumulation in A53T overexpressing PC12 cells.
Dynein knockdown also prompted the increase of microtubule-associated protein 1
light chain 3 (LC3-II) and sequestosome 1 (SQSTM1, p62) expression, and the
accumulation of autophagic vacuoles. Moreover, dynein suppression impaired the
autophagosome fusion with lysosome. In summary, our findings indicate that dynein
is critical for the clearance of aberrant alpha-synuclein via autophagosome
lysosome pathway.
PMID- 24351815
TI - Identification and characterization of seven glutathione S-transferase genes from
citrus red mite, Panonychus citri (McGregor).
AB - The citrus red mite, Panonychus citri (McGregor), is a global citrus pest, and
has developed severe resistance to several types of acaricides. However, the
molecular mechanisms of resistance in this mite remain unknown. In this study,
seven full-length cDNAs encoding glutathione S-transferases (GSTs) genes were
identified and characterized in P. citri. The effects of pyridaben and
fenpropathrin exposure on the expression of these genes were also investigated.
Phylogenetic analysis revealed that the seven GSTs genes in P. citri cloned in
this study belong to three different cytosolic classes, including four in mu, two
in delta and one in zeta. Among these seven GSTs genes, the relative expression
level of PcGSTm1 was significantly higher in adult than in the other life stages
(egg, larvae and nymph). Compared with the control, the mRNA levels of the seven
GST genes did not change significantly following exposure to pyridaben at LC10.
However, RT-qPCR results showed that, when exposed to LC10 of fenpropathrin, six
GSTs gene (PcGSTm1, PcGSTm3, PcGSTm4, PcGSTd1, PcGSTd2 and PcGSTz1) transcripts
increased in a time-dependent manner. This is the first insight into the
molecular characteristics of GSTs gene cDNAs in P. citri. The elevated GSTs gene
transcripts following exposure to fenpropathrin might be one of the mechanisms
involved in detoxification of this acaricide.
PMID- 24351816
TI - Effect of ion concentration changes in the limited extracellular spaces on
sarcolemmal ion transport and Ca2+ turnover in a model of human ventricular
cardiomyocyte.
AB - We have developed a computer model of human cardiac ventricular myocyte (CVM),
including t-tubular and cleft spaces with the aim of evaluating the impact of
accumulation-depletion of ions in restricted extracellular spaces on
transmembrane ion transport and ionic homeostasis in human CVM. The model was
based on available data from human CVMs. Under steady state, the effect of ion
concentration changes in extracellular spaces on [Ca2+]i-transient was explored
as a function of critical fractions of ion transporters in t-tubular membrane
(not documented for human CVM). Depletion of Ca2+ and accumulation of K+
occurring in extracellular spaces slightly affected the transmembrane Ca2+ flux,
but not the action potential duration (APD90). The [Ca2+]i-transient was reduced
(by 2%-9%), depending on the stimulation frequency, the rate of ion exchange
between t-tubules and clefts and fractions of ion-transfer proteins in the t
tubular membrane. Under non-steady state, the responses of the model to changes
of stimulation frequency were analyzed. A sudden increase of frequency (1-2.5 Hz)
caused a temporal decrease of [Ca2+] in both extracellular spaces, a reduction of
[Ca2+]i-transient (by 15%) and APD90 (by 13 ms). The results reveal different
effects of activity-related ion concentration changes in human cardiac t-tubules
(steady-state effects) and intercellular clefts (transient effects) in the
modulation of membrane ion transport and Ca2+ turnover.
PMID- 24351817
TI - Effect of the GLP-1 analog exendin-4 and oxaliplatin on intrahepatic
cholangiocarcinoma cell line and mouse model.
AB - The influence of Glucagon-like peptide-1 (GLP-1) and Exendin-4 on development of
intrahepatic cholangiocarcinoma (ICC) is evaluated in the study. In vitro tests,
including acute toxicity test, cell colony formation assays, cells proliferation
and apoptosis, transwell assay, were performed. An ICC in situ tumor animal model
was established. Then, animals were randomly divided into four groups (n = 6):
control, Exendin-4 treatment, oxaliplatin treatment and Exendin-4-oxaliplatin
treatment. Animals in the Exendin-4 treatment and Exendin-4-oxaliplatin treatment
groups received a subcutaneous injection of Exendin-4 (100 MUg/kg/day) for 1
week, and then received oxaliplatin (10 mg/kg/week) by tail vein injection.
Animals in the control group received PBS. Immunohistochemistry tests were used
for PCNA, Ki67, Caspase 3 expression in tumor tissue. Results show that that,
after incubation of human cholangiocarcinoma cell lines, HuCCTI and GLP-1, or
HuCCTI and Exendin-4, colony formation number was sharply decreased. However, GLP
1, HuCCTI or Exendin-4 did not affect the colony of normal cells. Combination
treatment with oxaliplatin and Exendin-4 can significantly inhibit tumor cells'
proliferation and promote apoptosis. The combined effect is stronger than that of
oxaliplatin or Exendin-4. Combination treatment with oxaliplatin and Exendin4 can
significantly decrease Ki67 and PCNA proteins' expression in subcutaneous tumors
of nude mice. The inhibitory effect of Combination treatment with oxaliplatin and
Exendin4 is clearly stronger than that of oxaliplatin. In addition, Combination
treatment with oxaliplatin and Exendin4 can significantly increase Caspase3
protein positive expression. In short, these results show that combination
treatment with oxaliplatin and Exendin4 can inhibit tumor cells' proliferation,
and promote apoptosis.
PMID- 24351818
TI - The preparation of capsaicin-chitosan microspheres (CCMS) enteric coated tablets.
AB - This study aimed to research the preparation and content determination of
capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets
were prepared with the method of wet granulation. Nine formulae were designed to
determine the optimal formula of the core tablet. Eudragit L100 was used to
prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation
variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS),
dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were
evaluated for drug release characteristics. The in vitro release was studied
using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without
ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets
showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8)
revealed that the prepared tablets were able to sustain drug release into the
intestine and a first-order release was obtained for capsaicin. This research is
the first report of the preparation and content determination of CCMS enteric
coated tablets. The sustained release behavior of enteric coated formulations in
pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery
platform for sustained delivery of gastric irritant drugs.
PMID- 24351819
TI - Comparability of in vitro tests for bioactive nanoparticles: a common assay to
detect reactive oxygen species as an example.
AB - The release of reactive oxygen species (ROS) during the electron transport of
mitochondrial aerobic respiration is the major source of ROS. However, contact
between cells and nanoparticles (NPs) can also induce release of ROS, leading to
an imbalance towards the pro-oxidative state. At low levels of ROS production,
cells initiate a protective response to guarantee their survival, but an excess
of ROS can damage cellular compounds such as membranes and various organelles, or
directly cause genotoxicity. Thus an elevated level of ROS is an important
indicator of cellular stress and an accurate recording of this parameter would be
very informative. ROS can be measured by various assays, but all known assays
measuring and quantifying ROS possess certain weaknesses. The problems and
challenges of quantitatively detecting ROS in vitro using the 2',7'
dichlorodihydrofluorescein (DCF) assay is discussed as an example. In addition,
we debate the difficulties in finding a suitable and stable chemical reaction
control for the DCF assay (or other ROS-detecting assays). As a conclusion, we
believe that using 3-morpholinosydnonimine hydrochloride (Sin-1) as a ROS inducer
in the DCF assay is feasible only qualitatively. However, a quantitative
measurement of the absolute amount of ROS produced and a quantitative comparison
between experiments is (at the moment) impossible.
PMID- 24351820
TI - Selection of reliable reference genes for gene expression studies in the biofuel
plant Jatropha curcas using real-time quantitative PCR.
AB - Jatropha curcas is a promising renewable feedstock for biodiesel and bio-jet fuel
production. To study gene expression in Jatropha in different tissues throughout
development and under stress conditions, we examined a total of 11 typical
candidate reference genes using real-time quantitative polymerase chain reaction
(RT-qPCR) analysis, which is widely used for validating transcript levels in gene
expression studies. The expression stability of these candidate reference genes
was assessed across a total of 20 samples, including various tissues at
vegetative and reproductive stages and under desiccation and cold stress
treatments. The results obtained using software qBasePLUS showed that the top
ranked reference genes differed across the sample subsets. The combination of
actin, GAPDH, and EF1alpha would be appropriate as a reference panel for
normalizing gene expression data across samples at different developmental
stages; the combination of actin, GAPDH, and TUB5 should be used as a reference
panel for normalizing gene expression data across samples under various abiotic
stress treatments. With regard to different developmental stages, we recommend
the use of actin and TUB8 for normalization at the vegetative stage and GAPDH and
EF1alpha for normalization at the reproductive stage. For abiotic stress
treatments, we recommend the use of TUB5 and TUB8 for normalization under
desiccation stress and GAPDH and actin for normalization under cold stress. These
results are valuable for future research on gene expression during development or
under abiotic stress in Jatropha. To our knowledge, this is the first report on
the stability of reference genes in Jatropha.
PMID- 24351821
TI - Effect of exogenous factors on bacteriocin production from Lactobacillus
paracasei J23 by using a resting cell system.
AB - A resting cell system was developed for bacteriocin Lac-B23 production from
Lactobacillus paracasei J23. The resting cell medium contained (g/L): Glucose 20,
Sodium acetate 5.0, MnSO4 0.25 MgSO4 0.5, Ammoniumhydrogencitrate 1.0, KH2PO4
1.0. The resting cell incubation time and temperature were 20 h and 37 degrees C
and the effects of exogenous factors, including amino acids, glycerol, pyruvic
acid, and alpha-ketoglutaric acid were investigated. Cys and Gly could stimulate
the production of bacteriocin, while no stimulus effect was observed for Glu, Tyr
and Ala. Glycerol and pyruvic acid increased bacteriocin production and the
optimum concentrations were 1% and 30 g/L, respectively. Bacteriocin could act as
an inducer of its own biosynthesis. These findings are of importance for the
further study of bacteriocin biosynthesis regulation and for the improvement of
bacteriocin production yields.
PMID- 24351822
TI - Improved bonding of partially osteomyelitic bone to titanium pins owing to
biomimetic coating of apatite.
AB - Increased fixation strength of the bone-pin interface is important for inhibiting
pin loosening after external fixation. In a previous study, an apatite (Ap) layer
was formed on anodically oxidized titanium (Ti) pins by immersing them in an
infusion fluid-based supersaturated calcium phosphate solution at 37 degrees C
for 48 h. In the present study, an Ap layer was also successfully formed using a
one-step method at 25 degrees C for 24 h in an infusion fluid-based
supersaturated calcium phosphate solution, which is clinically useful due to the
immersion temperature [corrected]. After percutaneous implantation in a proximal
tibial metaphysis for four weeks in rabbits (n = 20), the Ti pin coated with the
Ap layer showed significantly increased extraction torque compared with that of
an uncoated Ti screw even with partial osteomyelitis present, owing to dense bone
formation on the Ap layer in the cortical and medullary cavity regions. When the
infection status was changed from "no osteomyelitis" to "partial osteomyelitis,"
the extraction torque in the Ap group with "partial osteomyelitis" was almost
identical to that for "no osteomyelitis" cases. These results suggest that the Ap
layer formed by the room temperature process could effectively improve the
fixation strength of the Ti pin for external fixation clinically even with
partial osteomyelitis present.
PMID- 24351823
TI - Cardiac ablation of Rheb1 induces impaired heart growth, endoplasmic reticulum
associated apoptosis and heart failure in infant mice.
AB - Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of
cellular processes. In this study, we investigate the role of Rheb1 in the post
natal heart. We found that deletion of the gene responsible for production of
Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias,
heart failure, and premature death of these mice. In addition, heart growth
impairment, aberrant metabolism relative gene expression, and increased
cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the
development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt)
signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and
tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts.
Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1)
was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c
Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion,
this study demonstrates that Rheb1 is important for maintaining cardiac function
in post-natal mice via regulation of mTORC1 activity and stress on the
endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the
survival of mice with advanced heart failure. Thus, this study provides direct
evidence that Rheb1 performs multiple important functions in the heart of the
post-natal mouse. Enhancing Akt activity improves the survival of infant mice
with advanced heart failure.
PMID- 24351824
TI - Cbl-b enhances sensitivity to 5-fluorouracil via EGFR- and mitochondria-mediated
pathways in gastric cancer cells.
AB - 5-Fluorouracil (5-FU) is an essential component of anticancer chemotherapy
against gastric cancer. However, the response rate of single drug is still
limited. The ubiquitin ligase Cbl-b is a negative regulator of growth factor
receptor signaling and is involved in the suppression of cancer cell
proliferation. However, whether Cbl-b could affect 5-FU sensitivity remains
unclear. The present study showed that Cbl-b knockdown caused higher
proliferation concomitant with the decrease of apoptosis induced by 5-FU
treatment in gastric cancer cell. Further mechanism investigation demonstrated
that Cbl-b knockdown caused significant increase of phosphorylation of EGFR, ERK
and Akt, decrease of mitochondrial membrane potential, and increase of expression
ratio of Bcl-2/Bax. These results suggest that Cbl-b enhances sensitivity to 5-FU
via EGFR- and mitochondria-mediated pathways in gastric cancer cells.
PMID- 24351825
TI - Biological functional relevance of asymmetric dimethylarginine (ADMA) in
cardiovascular disease.
AB - There is growing evidence that increased levels of the endogenous NO synthase
inhibitor asymmetric dimethylarginine (ADMA) may contribute to endothelial
dysfunction. Studies in animal models as well as in humans have suggested that
the increase in ADMA occurs at a time when vascular disease has not yet become
clinically evident. ADMA competitively inhibits NO elaboration by displacing L
arginine from NO synthase. In a concentration-dependent manner, it thereby
interferes not only with endothelium-dependent, NO-mediated vasodilation, but
also with other biological functions exerted by NO. The upshot may be a pro
atherogenic state. Recently, several studies have investigated the effect of
various therapeutical interventions on ADMA plasma concentrations.
PMID- 24351826
TI - Maternal methyl donors supplementation during lactation prevents the
hyperhomocysteinemia induced by a high-fat-sucrose intake by dams.
AB - Maternal perinatal nutrition may program offspring metabolic features. Epigenetic
regulation is one of the candidate mechanisms that may be affected by maternal
dietary methyl donors intake as potential controllers of plasma homocysteine
levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary
groups during lactation: control, control supplemented with methyl donors, high
fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological
outcomes in the offspring were measured, including hepatic mRNA expression and
global DNA methylation after weaning. The newborns whose mothers were fed the
obesogenic diet were heavier longer and with a higher adiposity and intrahepatic
fat content. Interestingly, increased levels of plasma homocysteine induced by
the maternal high-fat-sucrose dietary intake were prevented in both sexes by
maternal methyl donors supplementation. Total hepatic DNA methylation decreased
in females due to maternal methyl donors administration, while Dnmt3a hepatic
mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore,
a negative association between Dnmt3a liver mRNA levels and plasma homocysteine
concentrations was found. Maternal high-fat-sucrose diet during lactation could
program offspring obesity features, while methyl donors supplementation prevented
the onset of high hyperhomocysteinemia. Maternal dietary intake also affected
hepatic DNA methylation metabolism, which could be linked with the regulation of
the methionine-homocysteine cycle.
PMID- 24351828
TI - Atorvastatin attenuates bleomycin-induced pulmonary fibrosis via suppressing iNOS
expression and the CTGF (CCN2)/ERK signaling pathway.
AB - Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality
rate. To date, despite the fact that extensive research trials are ongoing,
pulmonary fibrosis continues to have a poor response to available medical
therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors,
known for its broad pharmacological activities, remains a remedy against multiple
diseases. The present study investigated the antifibrotic potential of
atorvastatin against bleomycin-induced lung fibrosis and to further explore the
possible underlying mechanisms. Our results showed that atorvastatin
administration significantly ameliorated the bleomycin mediated histological
alterations and blocked collagen deposition with parallel reduction in the
hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA) level and lung
indices. Atorvastatin also markedly decreased the expression of inducible nitric
oxide synthase (iNOS) in lung tissues and, thus, prevented nitric oxide (NO)
release in response to bleomycin challenge. Furthermore, atorvastatin exhibited
target down-regulation of connective tissue growth factor (CTGF (CCN2)) and
phosphorylation extracellular regulated protein kinases (p-ERK) expression. Taken
together, atorvastatin significantly ameliorated bleomycin-induced pulmonary
fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2)/ERK
signaling pathway. The present study provides evidence that atorvastatin may be a
potential therapeutic reagent for the treatment of lung fibrosis.
PMID- 24351829
TI - Bioresorbable drug-eluting magnesium-alloy scaffold for treatment of coronary
artery disease.
AB - The introduction of metallic drug-eluting stents has reduced the risk of
restenosis and widened the indications of percutaneous coronary intervention in
treatment of coronary artery disease. However, this medical device can induce
hypersensitive reaction that interferes with the endothelialization and healing
process resulting in late persistent or acquired malapposition of the permanent
metallic implant. Delayed endotheliaization and malapposition may lead to late
and very late stent thrombosis. Bioresorbable scaffolds (BRS) have been
introduced to potentially overcome these limitations, as they provide temporary
scaffolding and then disappear, liberating the treated vessel from its cage.
Magnesium is an essential mineral needed for a variety of physiological functions
in the human body and its bioresorbable alloy has the strength-to-weight ratio
comparable with that of strong aluminum alloys and alloy steels. The aim of this
review is to present the new developments in Magnesium BRS technology, to
describe its clinical application and to discuss the future prospects of this
innovative therapy.
PMID- 24351827
TI - Oxidative stress and neurodegenerative disorders.
AB - Living cells continually generate reactive oxygen species (ROS) through the
respiratory chain during energetic metabolism. ROS at low or moderate
concentration can play important physiological roles. However, an excessive
amount of ROS under oxidative stress would be extremely deleterious. The central
nervous system (CNS) is particularly vulnerable to oxidative stress due to its
high oxygen consumption, weakly antioxidative systems and the terminal
differentiation characteristic of neurons. Thus, oxidative stress elicits various
neurodegenerative diseases. In addition, chemotherapy could result in severe side
effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a
growing body of evidence demonstrates the involvement of ROS in drug-induced
neurotoxicities as well. Therefore, development of antioxidants as
neuroprotective drugs is a potentially beneficial strategy for clinical therapy.
In this review, we summarize the source, balance maintenance and physiologic
functions of ROS, oxidative stress and its toxic mechanisms underlying a number
of neurodegenerative diseases, and the possible involvement of ROS in
chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value
for antioxidants as neuroprotective drugs and provide our comments on the unmet
needs.
PMID- 24351830
TI - Identification and biochemical characterization of protein phosphatase 5 from the
cantharidin-producing blister beetle, Epicauta chinensis.
AB - Protein phosphatase 5 (PP5) is a unique member of serine/threonine phosphatases
which has been recognized in regulation of diverse cellular processes. A cDNA
fragment encoding PP5 (EcPP5) was cloned and characterized from the cantharidin
producing blister beetle, E. chinensis. EcPP5 contains an open reading frame of
1500 bp that encodes a protein of 56.89 kDa. The deduced amino acid sequence
shares 88% and 68% identities to the PP5 of Tribolium castaneum and humans,
respectively. Analysis of the primary sequence shows that EcPP5 has three TPR
(tetratricopeptide repeat) motifs at its N-terminal region and contains a highly
conserved C-terminal catalytic domain. RT-PCR reveals that EcPP5 is expressed in
all developmental stages and in different tissues. The recombinant EcPP5 (rEcPP5)
was produced in Escherichia coli and purified to homogeneity. The purified
protein exhibited phosphatase activity towards pNPP (p-nitrophenyl phosphate) and
phosphopeptides, and its activity can be enhanced by arachidonic acid. In vitro
inhibition study revealed that protein phosphatase inhibitors, okadaic acid,
cantharidin, norcantharidin and endothall, inhibited its activity. Further,
protein phosphatase activity of total soluble protein extract from E. chinensis
adults could be impeded by these inhibitors suggesting there might be some
mechanism to protect this beetle from being damaged by its self-produced
cantharidin.
PMID- 24351831
TI - CYP 2D6 binding affinity predictions using multiple ligand and protein
conformations.
AB - Because of the large flexibility and malleability of Cytochrome P450 enzymes
(CYPs), in silico prediction of CYP binding affinities to drugs and other
xenobiotic compounds is a true challenge. In the current work, we use an
iterative linear interaction energy (LIE) approach to compute CYP binding
affinities from molecular dynamics (MD) simulation. In order to improve sampling
of conformational space, we combine results from simulations starting with
different relevant protein-ligand geometries. For calculated binding free
energies of a set of thiourea compounds binding to the flexible CYP 2D6 isoform,
improved correlation with experiment was obtained by combining results of MD runs
starting from distinct protein conformations and ligand-binding orientations.
This accuracy was obtained from relatively short MD simulations, which makes our
approach computationally attractive for automated calculations of ligand-binding
affinities to flexible proteins such as CYPs.
PMID- 24351832
TI - Cloud point extraction of parabens using non-ionic surfactant with cylodextrin
functionalized ionic liquid as a modifier.
AB - A cloud point extraction (CPE) process using non-ionic surfactant (DC193C) to
extract selected paraben compounds from water samples was investigated using
reversed phase high performance liquid chromatography (RP-HPLC). The CPE process
with the presence of beta-cyclodextrin (betaCD) functionalized ionic liquid as a
modifier (CPE-DC193C-betaCD-IL) is a new extraction technique that has been
applied on the optimization of parameters, i.e., pH, betaCD-IL concentration and
phase volume ratio. This CPE-DC193C-betaCD-IL method is facilitated at 30
degrees C, showing great losses of water content in the surfactant-rich phase,
resulting in a high pre-concentration factor and high distribution coefficient.
The developed method CPE-DC193C-betaCD-IL did show enhanced properties compared
to the CPE method without the modifier (CPE-DC193C). The developed method of CPE
DC193C-betaCD-IL gives an excellent performance on the detection of parabens from
water samples with the limit of detection falling in the range of 0.013-0.038 ug
mL-1. Finally, the inclusion complex formation, hydrogen bonding, and pi-pi
interaction between the betaCD-IL, benzyl paraben (ArP), and DC 193C were proven
using 1H NMR and 2D NOESY spectroscopy.
PMID- 24351833
TI - EGFR mutations in surgically resected fresh specimens from 697 consecutive
Chinese patients with non-small cell lung cancer and their relationships with
clinical features.
AB - We aimed to reveal the true status of epidermal growth factor receptor (EGFR)
mutations in Chinese patients with non-small cell lung cancer (NSCLC) after lung
resections. EGFR mutations of surgically resected fresh tumor samples from 697
Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System
(ARMS). Correlations between EGFR mutation hotspots and clinical features were
also explored. Of the 697 NSCLC patients, 235 (33.7%) patients had tyrosine
kinase inhibitor (TKIs) sensitive EGFR mutations in 41 (14.5%) of the 282
squamous carcinomas, 155 (52.9%) of the 293 adenocarcinomas, 34 (39.5%) of the 86
adenosquamous carcinomas, one (9.1%) of the 11 large-cell carcinomas, 2 (11.1%)
of the 18 sarcomatoid carcinomas, and 2 (28.6%) of the 7 mucoepidermoid
carcinomas. TKIs sensitive EGFR mutations were more frequently found in female
patients (p < 0.001), non-smokers (p = 0.047) and adenocarcinomas (p < 0.001).
The rates of exon 19 deletion mutation (19-del), exon 21 L858R point mutation
(L858R), exon 21 L861Q point mutation (L861Q), exon 18 G719X point mutations
(G719X, including G719C, G719S, G719A) were 43.4%, 48.1%, 1.7% and 6.8%,
respectively. Exon 20 T790M point mutation (T790M) was detected in 3 squamous
carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins) was
detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR
mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R
are two of the more frequent mutations. EGFR mutation detection should be
performed as a routine postoperative examination in Chinese NSCLC patients.
PMID- 24351834
TI - Towards lipidomics of low-abundant species for exploring tumor heterogeneity
guided by high-resolution mass spectrometry imaging.
AB - Many studies have evidenced the main role of lipids in physiological and also
pathological processes such as cancer, diabetes or neurodegenerative diseases.
The identification and the in situ localization of specific low-abundant lipid
species involved in cancer biology are still challenging for both fundamental
studies and lipid marker discovery. In this paper, we report the identification
and the localization of specific isobaric minor phospholipids in human breast
cancer xenografts by FTICR MALDI imaging supported by histochemistry. These
potential candidates can be further confirmed by liquid chromatography coupled
with electrospray mass spectrometry (LC-ESI-MS) after extraction from the region
of interest defined by MALDI imaging. Finally, this study highlights the
importance of characterizing the heterogeneous distribution of low-abundant lipid
species, relevant in complex histological samples for biological purposes.
PMID- 24351835
TI - A simple strategy for development of single nucleotide polymorphisms from non
model species and its application in Panax.
AB - Single nucleotide polymorphisms (SNPs) are widely employed in the studies of
population genetics, molecular breeding and conservation genetics. In this study,
we explored a simple route to develop SNPs from non-model species based on
screening the library of single copy nuclear genes (SCNGs). Through application
of this strategy in Panax, we identified 160 and 171 SNPs from P. quinquefolium
and P. ginseng, respectively. Our results demonstrated that both P. ginseng and
P. quinquefolium possessed a high level of nucleotide diversity. The number of
haplotype per locus ranged from 1 to 12 for P. ginseng and from 1 to 9 for P.
quinquefolium, respectively. The nucleotide diversity of total sites (piT) varied
between 0.000 and 0.023 for P. ginseng and 0.000 and 0.035 for P. quinquefolium,
respectively. These findings suggested that this approach is well suited for SNP
discovery in non-model organisms and is easily employed in standard genetics
laboratory studies.
PMID- 24351836
TI - Characterization of a kappa-carrageenase from marine Cellulophaga lytica strain
N5-2 and analysis of its degradation products.
AB - A carrageenan-degrading marine Cellulophaga lytica strain N5-2 was isolated from
the sediment of carrageenan production base. A kappa-carrageenase (EC 3.2.1.83)
with high activity was purified to electrophoretic homogeneity from the culture
supernatant by a procedure of ammonium sulfate precipitation, dialyzing and gel
filtration on SephadexG-200 and SephadexG-75. The purified enzyme was verified as
a single protein on SDS-PAGE, and whose molecular weight was 40.8 kDa. The kappa
carrageenase yielded a high activity of 1170 U/mg protein. For kappa-carrageenase
activity, the optimum temperature and pH were 35 degrees C and pH 7.0,
respectively. The enzyme was stable at 40 degrees C for at least 2.5 h. The
enzyme against kappa-carrageenan gave a Km value of 1.647 mg/mL and a Vmax value
of 8.7 MUmol/min/mg when the reaction was carried out at 35 degrees C and pH
7.0. The degradation products of the k-carrageenase were analyzed by thin layer
chromatography (TLC), high performance liquid chromatography (HPLC), electrospray
ionization time-of-flight mass spectroscopy (ESI-TOF-MS) and 13C-NMR
spectroscopy, and the results indicated that the enzyme was specific of the beta
1,4 linkage and hydrolyzed kappa-carrageenan into kappa-neocarraoctaose-sulfate
and kappa-neocarrahexaose-sulfate first, and then broke kappa-neocarraoctaose
sulfate into kappa-neocarrabiose-sulfate and kappa-neocarrahexaose-sulfate.
PMID- 24351837
TI - The antidiabetic drug metformin inhibits the proliferation of bladder cancer
cells in vitro and in vivo.
AB - Recent studies suggest that metformin, a widely used antidiabetic agent, may
reduce cancer risk and improve prognosis of certain malignancies. However, the
mechanisms for the anti-cancer effects of metformin remain uncertain. In this
study, we investigated the effects of metformin on human bladder cancer cells and
the underlying mechanisms. Metformin significantly inhibited the proliferation
and colony formation of 5637 and T24 cells in vitro; specifically, metformin
induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong
decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of
p21waf-1. Further experiments revealed that metformin activated AMP-activated
protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the
central regulator of protein synthesis and cell growth. Moreover, daily treatment
of metformin led to a substantial inhibition of tumor growth in a xenograft model
with concomitant decrease in the expression of proliferating cell nuclear antigen
(PCNA), cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that
metformin efficiently suppresses the proliferation of bladder cancer cells and
suggest that metformin may be a potential therapeutic agent for the treatment of
bladder cancer.
PMID- 24351838
TI - Preparation of magnetic carbon nanotubes (Mag-CNTs) for biomedical and
biotechnological applications.
AB - Carbon nanotubes (CNTs) have been widely studied for their potential applications
in many fields from nanotechnology to biomedicine. The preparation of magnetic
CNTs (Mag-CNTs) opens new avenues in nanobiotechnology and biomedical
applications as a consequence of their multiple properties embedded within the
same moiety. Several preparation techniques have been developed during the last
few years to obtain magnetic CNTs: grafting or filling nanotubes with magnetic
ferrofluids or attachment of magnetic nanoparticles to CNTs or their polymeric
coating. These strategies allow the generation of novel versatile systems that
can be employed in many biotechnological or biomedical fields. Here, we review
and discuss the most recent papers dealing with the preparation of magnetic CNTs
and their application in biomedical and biotechnological fields.
PMID- 24351839
TI - Expression pattern of Class B gene PAP3 in flower development of pepper.
AB - Class B gene APETALA3 (AP3) plays a key role in the development of petals and
stamens. Here, we investigated the expression pattern of PAP3 gene (genbank
accession number: HM104635) in the buds of cytoplasmic male sterility line 121A
and its near-isogenic restorer line 121C at four developmental stages and
analyzed the possible association between Class B genes and cytoplasmic male
sterility of pepper. Semi-quantitative PCR and quantitative real-time RT-PCR (qRT
PCR) as well as RNA in situ hybridization showed increased expression of PAP3 at
late phase of anther development and its higher expression in restorer line
compared with sterility line indicating PAP3's role at late developmental stage
of anther and suppressed expression in sterility line. RNA in situ hybridization
showed Class B gene features: high abundance in stamen and petal; lower
expression in pistil; no expression in sepal. Results of transient expression in
onion epidermal cells also showed PAP3 localized in the nucleus, which is
consistent with the expression pattern of transcription factors of MADS-box gene
family.
PMID- 24351840
TI - Human interleukin 23 receptor induces cell apoptosis in mammalian cells by
intrinsic mitochondrial pathway associated with the down-regulation of
RAS/mitogen-activated protein kinase and signal transducers and activators of
transcription factor 3 signaling pathways.
AB - The composition of IL-23R complex is similar to that of the IL-12 receptor (IL
12R) complex with a shared IL-12R-beta1 chain. The IL-12R-beta1 heterodimerizes
with IL-23R and IL-12R-beta2 to form IL-23R and IL-12R complexes, respectively.
The IL-12R-beta2 has been shown to function as a tumor suppressor gene and
apoptotic inducer. However, whether IL-23R also functions in cell apoptosis is
currently unknown. In this study, we demonstrate for the first time that
overexpression of IL-23R markedly induces cell apoptosis in both 293ET and HeLa
cells. The activations of caspase 3 and caspase 9 are induced by IL-23R.
Mechanistic study reveals that IL-23R markedly inhibits RAS/MAPK and STAT3 but
not STAT1 and PI-3K/Akt signaling pathways in both 293ET and HeLa cells.
Overexpression of IL-23R significantly up-regulates IL-12Rbeta1 expression but
not IL-23alpha and IL-12beta expressions in both cell lines. Therefore, our data
strongly indicates that IL-23R is able to induce cell apoptosis by activating the
intrinsic mitochondrial pathways associated with the inhibition in RAS/MAPK and
STAT3 activations in mammalian cells.
PMID- 24351841
TI - Synthesis, characterisation, and evaluation of a cross-linked disulphide amide
anhydride-containing polymer based on cysteine for colonic drug delivery.
AB - The use of disulphide polymers, a low redox potential responsive delivery, is one
strategy for targeting drugs to the colon so that they are specifically released
there. The objective of this study was to synthesise a new cross-linked
disulphide-containing polymer based on the amino acid cysteine as a colon drug
delivery system and to evaluate the efficiency of the polymers for colon targeted
drug delivery under the condition of a low redox potential. The disulphide cross
linked polymers were synthesised via air oxidation of 1,2-ethanedithiol and 3
mercapto-N-2-(3-mercaptopropionamide)-3-mercapto propionic anhydride (trithiol
monomers) using different ratio combinations. Four types of polymers were
synthesised: P10, P11, P151, and P15. All compounds synthesised were
characterised by NMR, IR, LC-MS, CHNS analysis, Raman spectrometry, SEM-EDX, and
elemental mapping. The synthesised polymers were evaluated in chemical reduction
studies that were performed in zinc/acetic acid solution. The suitability of each
polymer for use in colon-targeted drug delivery was investigated in vitro using
simulated conditions. Chemical reduction studies showed that all polymers were
reduced after 0.5-1.0 h, but different polymers had different thiol
concentrations. The bacterial degradation studies showed that the polymers were
biodegraded in the anaerobic colonic bacterial medium. Degradation was most
pronounced for polymer P15. This result complements the general consensus that
biodegradability depends on the swellability of polymers in an aqueous
environment. Overall, these results suggest that the cross-linked disulphide
containing polymers described herein could be used as coatings for drugs
delivered to the colon.
PMID- 24351842
TI - Importance of H-abstraction in the final step of nitrosoalkane formation in the
mechanism-based inactivation of cytochrome P450 by amine-containing drugs.
AB - The metabolism of amine-containing drugs by cytochrome P450 enzymes (P450s) is
prone to form a nitrosoalkane metabolic intermediate (MI), which subsequently
coordinates to the heme iron of a P450, to produce a metabolic-intermediate
complex (MIC). This type of P450 inhibition, referred to as mechanism-based
inactivation (MBI), presents a serious concern in drug discovery processes. We
applied density functional theory (DFT) to the reaction between N
methylhydroxylamine (NMH) and the compound I reactive species of P450, in an
effort to elucidate the mechanism of the putative final step of the MI formation
in the alkylamine metabolism. Our DFT calculations show that H-abstraction from
the hydroxyl group of NMH is the most favorable pathway via which the
nitrosoalkane intermediate is produced spontaneously. H-abstraction from the N-H
bond was slightly less favorable. In contrast, N-oxidation and H-abstraction from
the C-H bond of the methyl group had much higher energy barriers. Hence, if the
conversion of NMH to nitrosoalkane is catalyzed by a P450, the reaction should
proceed preferentially via H-abstraction, either from the O-H bond or from the N
H bond. Our theoretical analysis of the interaction between the MI and
pentacoordinate heme moieties provided further insights into the coordination
bond in the MIC.
PMID- 24351844
TI - betaArrestins in cardiac G protein-coupled receptor signaling and function:
partners in crime or "good cop, bad cop"?
AB - betaArrestin (betaarr)-1 and -2 (betaarrs) (or Arrestin-2 and -3, respectively)
are universal G protein-coupled receptor (GPCR) adapter proteins expressed
abundantly in extra-retinal tissues, including the myocardium. Both were
discovered in the lab of the 2012 Nobel Prize in Chemistry co-laureate Robert
Lefkowitz, initially as terminators of signaling from the beta-adrenergic
receptor (betaAR), a process known as functional desensitization. They are now
known to switch GPCR signaling from G protein-dependent to G protein-independent,
which, in the case of betaARs and angiotensin II type 1 receptor (AT1R), might be
beneficial, e.g., anti-apoptotic, for the heart. However, the specific role(s) of
each betaarr isoform in cardiac GPCR signaling and function (or dysfunction in
disease), remain unknown. The current consensus is that, whereas both betaarr
isoforms can desensitize and internalize cardiac GPCRs, they play quite different
(even opposing in certain instances) roles in the G protein-independent signaling
pathways they initiate in the cardiovascular system, including in the myocardium.
The present review will discuss the current knowledge in the field of betaarrs
and their roles in GPCR signaling and function in the heart, focusing on the
three most important, for cardiac physiology, GPCR types (beta1AR, beta2AR &
AT1R), and will also highlight important questions that currently remain
unanswered.
PMID- 24351846
TI - Model-based registration for assessment of spinal deformities in idiopathic
scoliosis.
AB - Detailed analysis of spinal deformity is important within orthopaedic healthcare,
in particular for assessment of idiopathic scoliosis. This paper addresses this
challenge by proposing an image analysis method, capable of providing a full
three-dimensional spine characterization. The proposed method is based on the
registration of a highly detailed spine model to image data from computed
tomography. The registration process provides an accurate segmentation of each
individual vertebra and the ability to derive various measures describing the
spinal deformity. The derived measures are estimated from landmarks attached to
the spine model and transferred to the patient data according to the registration
result. Evaluation of the method provides an average point-to-surface error of
0.9 mm +/- 0.9 (comparing segmentations), and an average target registration
error of 2.3 mm +/- 1.7 (comparing landmarks). Comparing automatic and manual
measurements of axial vertebral rotation provides a mean absolute difference of
2.5 degrees +/- 1.8, which is on a par with other computerized methods for
assessing axial vertebral rotation. A significant advantage of our method,
compared to other computerized methods for rotational measurements, is that it
does not rely on vertebral symmetry for computing the rotational measures. The
proposed method is fully automatic and computationally efficient, only requiring
three to four minutes to process an entire image volume covering vertebrae L5 to
T1. Given the use of landmarks, the method can be readily adapted to estimate
other measures describing a spinal deformity by changing the set of employed
landmarks. In addition, the method has the potential to be utilized for accurate
segmentations of the vertebrae in routine computed tomography examinations, given
the relatively low point-to-surface error.
PMID- 24351843
TI - Multidrug resistance and cancer stem cells in neuroblastoma and hepatoblastoma.
AB - Chemotherapy is one of the major modalities in treating cancers. However, its
effectiveness is limited by the acquisition of multidrug resistance (MDR).
Several mechanisms could explain the up-regulation of MDR genes/proteins in
cancer after chemotherapy. It is known that cancer stem cells (CSCs) play a role
as master regulators. Therefore, understanding the mechanisms that regulate some
traits of CSCs may help design efficient strategies to overcome chemoresistance.
Different CSC phenotypes have been identified, including those found in some
pediatric malignancies. As solid tumors in children significantly differ from
those observed in adults, this review aims at providing an overview of the
mechanistic relationship between MDR and CSCs in common solid tumors, and, in
particular, focuses on clinical as well as experimental evidence of the relations
between CSCs and MDR in neuroblastoma and hepatoblastoma. Finally, some novel
approaches, such as concomitant targeting of multiple key transcription factors
governing the stemness of CSCs, as well as nanoparticle-based approaches will
also be briefly addressed.
PMID- 24351845
TI - Necrostatin-1 attenuates ischemia injury induced cell death in rat tubular cell
line NRK-52E through decreased Drp1 expression.
AB - Necrostatin-1 (Nec-1) inhibits necroptosis and is usually regarded as having no
effect on other cell deaths. Here, this study explored whether the addition of
Nec-1 has an effect on cell death induced by simulated ischemia injury in rat
tubular cell line NRK-52E. In addition, we also investigated the mechanism of Nec
1 attenuates cell death in this renal ischemia model. The NRK-52E cells were
incubated with TNF-alpha + antimycinA (TA) for 24 h with or without Nec-1. Cell
death was observed under fluorescent microscope and quantified by flow cytometry.
Cell viabilities were detected by MTT assay. The protein expression of dynamin
related protein 1 (Drp1) was detected by Western blotting and immunofluorescence
assay. Increased cell death in simulated ischemia injury of NRK-52E cells were
markedly attenuated in the Nec-1 pretreated ischemia injury group. Meanwhile,
cell viability was significantly improved after using Nec-1. In addition, we also
observed that the protein expression of Drp1, a mediator of mitochondrial
fission, was significantly increased in simulated ischemia injury group.
Increased Drp1 expression in the ischemia injury group can be abolished by Nec-1
or Drp1-knock down, accompanied with decreased cell death and improved cell
viabilities. These results suggest that Nec-1 may inhibit cell death induced by
simulated ischemia injury in the rat tubular cell line NRK-52E through decreased
Drp1 expression.
PMID- 24351847
TI - Ultrasound effects on the assembly of casein micelles in reconstituted skim milk.
AB - Reconstituted skim milks (10 % w/w total solids, pH 6.7-8.0) were ultrasonicated
(20, 400 or 1600 kHz at a specific energy input of 286 kJ/kg) at a bulk milk
temperature of <30 degrees C. Application of ultrasound to milk at different pH
altered the assembly of the casein micelle in milk, with greater effects at
higher pH and lower frequency. Low frequency ultrasound caused greater disruption
of casein micelles causing release of protein from the micellar to the serum
phase than high frequency. The released protein re-associated to form aggregates
of smaller size but with surface charge similar to the casein micelles in the
original milk. Ultrasound may be used as a physical intervention to alter the
size of the micelles and the partitioning of caseins between the micellar and
serum phases in milk. The altered protein equilibria induced by ultrasound
treatment may have potential for the development of milk with novel
functionality.
PMID- 24351848
TI - Evaluation of the relationship between high maternal weight and the duration of
different stages of labor, delivery rout, neonatal weight and Apgar score.
AB - SUMMARY: OBJECTIVES: To evaluate the relationship between high maternal weight
and the duration of different stages of labor, delivery rout, and neonatal weight
and Apgar score. METHODS: A comparative prospective study was performed on 240
eligible women, who were divided into two groups. The control group (n = 120),
whose their pre-pregnancy or first trimester weight were normal with body mass
index (BMI) between 19.8 and 26 kg/m(2), and the case group (n = 120), whose pre
pregnancy or first trimester weight were high, with BMI between 26 and 30
kg/m(2). The progress of labor and delivery in these two groups were followed and
the duration of different stages of labor, delivery rout, and neonatal weight and
Apgar score were compared between these two groups. RESULTS: The mean BMI in the
case and control group were 28.34 +/- 2.02 and 22.03 +/- 3.83, respectively (P =
0.001). There were no statistically significant differences between the two
groups according to the duration of first, second, and third stages of labor and
delivery rout and neonatal Apgar score, but the neonatal weight was higher in the
case group (3670.8 +/- 456.4 g vs. 3511.7 +/- 452.7 g, P = 0.007, t = 2.71). With
maternal weight gain during pregnancy of more than 12 kg, the duration of the
first stage of labor was statistically higher in the case group (235.9 +/- 105.3
min vs. 167.2 +/- 75.6 min, P = 0.011, t = 2.64). Oxytocin was used for
augmentation of labor more, in the case group [43 women (64.2%) vs. 36 women
(44.4%), P = 0.017, X(2) = 5.74]. CONCLUSION: High maternal weight does not have
impact on the duration of labor and delivery rout, but can increase neonatal
weight and necessity for oxytocin, during labor.
PMID- 24351849
TI - Circulating levels of ganglioside GM3 in metabolic syndrome: A pilot study.
AB - SUMMARY: BACKGROUND: Insulin resistance is a characteristic feature of metabolic
syndrome. Ganglioside GM3 [alpha-Neu5Ac-(2-3)-beta-Gal-(1-4)-beta-Glc-(1-1)
ceramide] may impair insulin sensitivity in adipose tissue. We investigated the
relationship between serum GM3 levels and adiposity indices, as well as between
serum GM3 levels and metabolic risk variables. METHODS: Study 1: we assessed
serum GM3 levels in normal subjects and in patients with hyperglycemia and/or
hyperlipidemia (HL). Study 2: we investigated the relationship between serum GM3
levels and metabolic risk variables in patients with type 2 diabetes. RESULTS:
Study 1: serum GM3 levels were higher in hyperglycemic patients (1.4-fold),
hyperlipidemic patients (1.4-fold) and hyperglycemic patients with hyperlipidemia
(1.6-fold), than in normal subjects. Study 2: serum GM3 levels were significantly
increased in type 2 diabetic patients with severe obesity (visceral fat area
(VFA) >200 cm(2), BMI > 30). The GM3 level was positively correlated with LDL-c
(0.403, p = 0.012) in type 2 diabetes mellitus, but not affected by blood
pressure. In addition, the high levels of small dense LDL (>10 mg/dL) were
associated with the elevation of GM3. CONCLUSIONS: Serum GM3 levels was affected
by glucose and lipid metabolism abnormalities and by visceral obesity. GM3 may be
a useful marker for severity of metabolic syndrome.
PMID- 24351850
TI - Administration of phytosterols isolated from Aloe vera gel reduce visceral fat
mass and improve hyperglycemia in Zucker diabetic fatty (ZDF) rats.
AB - SUMMARY: We examined the effects of lophenol (Lo) and cycloartanol (Cy), minor
phytosterols of Aloe vera gel, in obese animal model of type II diabetes, Zucker
diabetic fatty (ZDF) rats. Male ZDF rats were administered Lo and Cy at 25
MUg/(kg day) daily for 44 days. Consecutive treatment of phytosterols suppressed
the hyperglycemia, and random blood glucose levels after 35 days of treatment
were 39.6 and 37.2% lower than the control, in Lo and Cy treatment groups,
respectively. Consistent with the random blood glucose level, hemoglobin A1c
(HbA1c) values of phytosterols treated rats were also lower than the control (Lo:
5.5 +/- 0.8, Cy: 4.6 +/- 0.7 vs. control: 7.2 +/- 1.5). In the oral glucose
tolerance test (OGTT) after 28 days of administration, the glucose intolerance
was improved in phytosterols treatment groups. Additionally, the continuous
administration of Lo and Cy also reduced the serum free fatty acid (FFA) and
triglyceride (TG) levels except total cholesterol (T-Cho). Furthermore, the
weights of total abdominal fat tissues were significantly lower than the control
in ZDF rats with Lo (27.7%) and Cy (26.3%) treatment. These observations suggest
that Aloe vera-derived phytosterols could reduce visceral fat accumulation, and
would be useful for the improvement of hyperlipidemia and hyperglycemia.:
PMID- 24351851
TI - Overweight and obesity in 4-year-old South Australian children and the stability
of IOTF cut points in this age group.
AB - SUMMARY: OBJECTIVE: To assess the validity of internationally accepted mid-year
cut points for overweight and obesity in children and their application for
ongoing surveillance. DATA: A large (n = 114,925) state wide administrative data
set of preschool children (aged 48-60 months) in South Australia including
measured height and weight, collected at various points in the fifth year of life
by the Children, Youth and Women's Health Service (CYWHS) between 1995 and 2003.
METHODS: Prevalence of overweight and obesity were calculated for each year of
the data set between 1995 and 2003. The international mid-year cut points were
compared to cut points for each month of age throughout the fifth year of life.
RESULTS: The prevalence of overweight and obesity in this age group has increased
significantly over the period for both males and females. The estimates of
overweight and obesity prevalence for both males and females calculated using the
mid-year cut points were not significantly different to cut points for each month
of age in both genders. CONCLUSIONS: The body mass index of children does not
vary significantly through the fifth year of life and prevalence estimates can be
obtained at any point in the fifth or sixth year of age for surveillance
purposes.
PMID- 24351852
TI - Weight reduction improves sleep, sleepiness and metabolic status in obese sleep
apnoea patients.
AB - SUMMARY: METHOD: In this prospective intervention study, 33 obese patients with
obstructive sleep apnoea syndrome (OSAS) (24 men, 9 women) were consecutively
enrolled for a weight reduction program at the Obesity Unit, Karolinska
University Hospital. 23 of 33 patients used OSAS-device, 19 with Continuous
Positive Airway Pressure and 4 with Mandibular Retaining Device. The patients
were investigated with questionnaires, blood tests and ambulant nocturnal
polysomnography before and after a 6-month program. Patients with OSAS-device
slept without it during the sleep studies. The intervention consisted of 8 weeks
low calorie diet and group meetings, followed by a day-care program of behaviour
change support. RESULTS: 27 of 33 patients (82%, 21 men and 6 women) completed
the study. After the intervention there were highly significant decreases (p <
0.001) in Body Mass Index from mean(S.D.) 40(5) to 34(3), apnoea-hypopnoea index
from 43(24) to 26(20) and Epworth Sleepiness Scale (ESS)-score from 9(4) to 6(4).
Sleep quality (arousal index, sleep efficiency, percentage deep sleep) and
metabolic status (blood pressure, blood glucose levels, lipidemia) were also
significantly improved. There was a significant correlation between increased
percentage deep sleep and reduced ESS-score. There were no differences due to
gender or use/no use of OSAS-device. CONCLUSION: The results suggest that weight
loss, induced by low calorie diet and behaviour change support, significantly
improves nocturnal respiratory parameters, sleep quality, daytime sleepiness and
metabolic status in obese OSAS patients after 6 months.
PMID- 24351853
TI - Should overweight and obese primary care patients be offered a meal replacement
diet?
AB - SUMMARY: OBJECTIVES: Randomized controlled pilot study of the impact of a 30-day
meal replacement (MR) diet on body weight. METHODS: Sixty-three subjects were
enrolled and randomized into two groups to test the hypothesis that a simple diet
based on packaged foods is as effective as a standard heart-healthy diet. Both
groups were given 1200 cal diets with unlimited fresh vegetables and fruits.
Eligible subjects were adult primary care patients with body mass index (BMI) >
25. Weights were measured in clinic at baseline and after 30 days. RESULTS:
Outcome data were available for 55 (44 women and 11 men). Ages ranged from 25 to
74. BMIs at baseline ranged from 24.5 to 50.6. Mean weight loss was similar in
the two groups (-2.7 +/- 2.6 kg in the meal replacement subjects vs. -3.3 +/- 2.2
in standard care, p = 0.35). CONCLUSION: The average adult primary care patient
who receives a single motivational interview can lose about 3 kg in 1 month using
meal replacements.
PMID- 24351854
TI - Measurement of visceral fat by abdominal bioelectrical impedance analysis is
beneficial in medical checkup.
AB - SUMMARY: OBJECTIVE: In addition to the waist circumference (WC) measurement, an
accurate measurement of visceral fat is very important in terms of the pathology
associated with the metabolic syndrome. The only method available for an accurate
measurement of a visceral fat area (VFA) is abdominal computed tomography (CT).
To overcome this limitation, we estimated VFA using abdominal bioelectrical
impedance analysis (BIA) with accuracy comparable to that of abdominal CT, and
investigated the relationship between VFA and risk factors of the metabolic
syndrome. Because abdominal BIA detects excess visceral fat accumulation that
cannot be detected by a measurement of WC, the characteristics of the subjects
who were identified as having excessive visceral fat using BIA, but not WC, were
examined. METHODS: Abdominal BIA was used to estimate VFA in male subjects (n =
1803) (age: 48 +/- 10 years, body mass index: 23.9 +/- 3.0 kg/m(2)) who provided
informed consent. RESULTS: The prevalence of the metabolic syndrome diagnosed
based on the diagnostic criteria established by the Japanese Society of Internal
Medicine was 18%. Among the risk factors of the metabolic syndrome, WC was
significantly correlated with triglycerides (TG), but estimated VFA was
correlated with blood pressure and HDL-cholesterol (HDL-C), in addition to TG.
Abdominal BIA detected excess visceral fat accumulation in 3% of subjects for
whom WC had detected none. Elevated blood pressure, TG, and fasting plasma
glucose and decreased HDL-C were also noted in these subjects, and the values of
these risk factors were comparable to those of subjects in whom visceral fat
accumulation was detected using WC. CONCLUSION: Abdominal BIA is a simple and
safe method that is superior to WC for the detection of excessive visceral fat
accumulation. Therefore, abdominal BIA will likely be used clinically to detect
excessive accumulation of visceral fat, which is an important predictor of the
metabolic syndrome.
PMID- 24351855
TI - Validity of clinical body weight measures as substitutes for missing data in a
randomized trial.
AB - SUMMARY: BACKGROUND: Long-term follow-up of weight loss interventions is
essential, but collecting weights can be difficult, and self-reports inaccurate.
We examined the relationship between weight measures obtained in the context of a
weight loss trial and in routine clinical care. METHODS: Body weight data from a
trial of behavioral obesity treatment among 88 obese women and 203 women age 40
65 years with comorbid obesity and depression were compared against weight data
entered into an electronic medical record (EMR) during routine clinical care.
Study and EMR weights and weight changes were then compared at 6 and 12 months
using scatterplots, Pearson's correlations, and t-tests. RESULTS: The 12-month
follow-up rate for this trial was 77%. Among the 224 12-month completers, 142
women (63%) had an EMR weight within 90 days of their 12-month study weight.
Study and EMR weights were highly correlated (0.99), with a mean difference of
0.1 kg. The correlation between two measures of 12-month weight change using
study and EMR weights was 0.96. These results were robust to sensitivity analyses
that explored the impact of different-sized windows for matching clinical weights
with study weights. Among the 67 women who were missing study weights at 12
months, 33 (49%) had an EMR weight available within 90 days of their missed
follow-up appointment. CONCLUSIONS: Weight measures routinely obtained in
clinical care are highly correlated with those obtained by trained research staff
and may be used, without statistical correction, to achieve higher rates of long
term follow-up in weight loss studies.
PMID- 24351857
TI - Dynamic electron arc radiotherapy (DEAR): a feasibility study.
AB - Compared to other radiation therapy modalities, clinical electron beam therapy
has remained practically unchanged for the past few decades even though electron
beams with multiple energies are widely available on most linacs. In this paper,
we present the concept of dynamic electron arc radiotherapy (DEAR), a new
conformal electron therapy technique with synchronized couch motion. DEAR
utilizes combination of gantry rotation, couch motion, and dose rate modulation
to achieve desirable dose distributions in patient. The electron applicator is
kept to minimize scatter and maintain narrow penumbra. The couch motion is
synchronized with the gantry rotation to avoid collision between patient and the
electron cone. In this study, we investigate the feasibility of DEAR delivery and
demonstrate the potential of DEAR to improve dose distributions on simple
cylindrical phantoms. DEAR was delivered on Varian's TrueBeam linac in Research
Mode. In conjunction with the recorded trajectory log files, mechanical motion
accuracies and dose rate modulation precision were analyzed. Experimental and
calculated dose distributions were investigated for different energies (6 and 9
MeV) and cut-out sizes (1*10 cm(2) and 3*10 cm(2) for a 15*15 cm(2) applicator).
Our findings show that DEAR delivery is feasible and has the potential to deliver
radiation dose with high accuracy (root mean square error, or RMSE of <0.1 MU,
<0.1 degrees gantry, and <0.1 cm couch positions) and good dose rate precision
(1.6 MU min(-1)). Dose homogeneity within +/-2% in large and curved targets can
be achieved while maintaining penumbra comparable to a standard electron beam on
a flat surface. Further, DEAR does not require fabrication of patient-specific
shields. These benefits make DEAR a promising technique for conformal
radiotherapy of superficial tumors.
PMID- 24351856
TI - An integrative study of the genetic, social and environmental determinants of
chronic kidney disease characterized by tubulointerstitial damages in the North
Central Region of Sri Lanka.
AB - OBJECTIVES: Previous investigations on chronic kidney disease of unknown etiology
characterized by tubulointerstitial damages (CKDu) in the North Central Region
(NCR) of Sri Lanka have supported the involvement of social, environmental and
genetic factors in its pathogenesis. METHODS: We conducted a social-environmental
and-genetic epidemiology study on a male population in NCR to investigate the
genetic and environmental contributors. We recruited 311 case-series patients and
504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated
because of the presence of hypertension, proteinuria, high HbA1c, high serum
creatinine or high alpha-1 microglobulin in urine. RESULTS AND DISCUSSION: None
of 18 metals measured (MUg//) in urine, including Cd, As and Pb, showed
significantly higher concentrations in cases compared with controls. As
speciation results showed that 75-80% of total urinary As was in the form of
arsenobetaine, which is non-toxic to humans. None of the metal concentrations in
drinking water samples exceeded guideline values. A genome-wide association study
(GWAS) was conducted to determine the genetic contributors. The GWAS yielded a
genome-wide significant association with CKDu for a single nucleotide
polymorphism (SNP; rs6066043; p=5.23 * 10(-9) in quantitative trait locus
analysis; p=3.73 * 10(-9) in dichotomous analysis) in SLC13A3 (sodium-dependent
dicarboxylate transporter member 3). The population attributable fraction and
odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified
as the major risk factor for CKDu. However, 43% of the apparently healthy male
population suffers from non-communicable diseases, suggesting their possible
influence on CKDu progression.
PMID- 24351858
TI - Optimisation of medium composition for probiotic biomass production using
response surface methodology.
AB - This study was aimed to optimise lactose, inulin and yeast extract concentration
and also culture pH for maximising the growth of a probiotic bacterium,
Bifidobacterium animalis subsp. lactis in apple juice and to assess the effects
of these factors by using response surface methodology. A second-order central
composite design was applied to evaluate the effects of these independent
variables on growth of the microorganism. A polynomial regression model with
cubic and quadratic terms was used for analysis of the experimental data. It was
found that the effects involving inulin, yeast extract and pH on growth of the
bacterium were significant, and the strongest effect was given by the yeast
extract concentration. Estimated optimum conditions of the factors on the
bacterial growth are as follows: lactose concentration=9.5 g/l; inulin
concentration=38.5 mg/l; yeast extract concentration=9.6 g/l and initial pH=6.2.
PMID- 24351859
TI - Disjoining pressure and the film-height-dependent surface tension of thin liquid
films: new insight from capillary wave fluctuations.
AB - In this paper we review simulation and experimental studies of thermal capillary
wave fluctuations as an ideal means for probing the underlying disjoining
pressure and surface tensions, and more generally, fine details of the
Interfacial Hamiltonian Model. We discuss recent simulation results that reveal a
film-height-dependent surface tension not accounted for in the classical
Interfacial Hamiltonian Model. We show how this observation may be explained
bottom-up from sound principles of statistical thermodynamics and discuss some of
its implications.
PMID- 24351860
TI - President's perspective: dual eligible--what does it mean and why should you know
about it?
PMID- 24351861
TI - Verifiable hypotheses for thymosin beta4-dependent and -independent angiogenic
induction of Trichinella spiralis-triggered nurse cell formation.
AB - Trichinella spiralis has been reported to induce angiogenesis for nutrient supply
and waste disposal by the induction of the angiogenic molecule vascular
endothelial cell growth factor (VEGF) during nurse cell formation. However, the
action mechanism to induce VEGF in nurse cells by T. spiralis is not known.
Hypoxia in nurse cells was suggested as a possible mechanism; however, the
presence of hypoxic conditions in infected muscle or nurse cells and whether
hypoxia indeed induces the expression of VEGF and subsequent angiogenesis in the
infected muscle are both a matter of debate. Our recent studies have shown that
thymosin beta4, a potent VEGF inducing protein, is expressed in the very early
stages of T. spiralis muscle infection suggesting the induction of VEGF in early
stage nurse cells. Nevertheless, we now show that hypoxic conditions were not
detected in any nurse cell stage but were detected only in the accumulated
inflammatory cells. These studies propose that induction of angiogenesis by VEGF
in T. spiralis-infected nurse cells was mediated by thymosin beta4 and is
unrelated to hypoxic conditions.
PMID- 24351862
TI - p27 Is a critical prognostic biomarker in non-alcoholic steatohepatitis-related
hepatocellular carcinoma.
AB - Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver
disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC).
As the number of patients studied to date has been limited, clinically useful
prognostic biomarkers of NASH-related HCC have not been available. In this study,
we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC.
p27 has been regarded as a prognostic factor in various types of cancer patients.
A total of 22 cases with NASH-related HCC were analyzed for p27 protein
expression, and phosphorylation at threonine 157 (T157) and serine 10 (S10) by
immunohistochemical analysis. The correlation of p27 with tumor characteristics,
disease-free survival (DFS), and overall survival was analyzed. p27 expression
was decreased in 13 HCCs (59%), and was significantly correlated with enlarged
tumor size (p = 0.01) and increased cell proliferation (p < 0.01). Phospho-p27 at
T157 and S10 was detected in four (18%) and seven (32%) cases, respectively, and
patients positive for phospho-p27 (S10) showed reduced DFS (hazard ratio 7.623, p
= 0.016) by univariate analysis. Further studies with more patients are required
to verify the usefulness of p27 as a biomarker for predicting tumor recurrence in
NASH patients.
PMID- 24351863
TI - Transcriptional profiling of hilar nodes from pigs after experimental infection
with Actinobacillus pleuropneumoniae.
AB - The gram-negative bacterium Actinobacillus pleuropneumoniae (APP) is an
inhabitant of the porcine upper respiratory tract and the causative agent of
porcine pleuropneumonia (PP). In recent years, knowledge about the
proinflammatory cytokine and chemokine gene expression that occurs in lung and
lymph node of the APP-infected swine has been advanced. However, systematic gene
expression profiles on hilar nodes from pigs after infection with Actinobacillus
pleuropneumoniae have not yet been reported. The transcriptional responses were
studied in hilar nodes (HN) from swine experimentally infected with APP and the
control groupusing Agilent Porcine Genechip, including 43,603 probe sets. 9,517
transcripts were identified as differentially expressed (DE) at the p <= 0.01
level by comparing the log2 (normalized signal) of the two groups named treatment
group (TG) and controls (CG). Eight hundred and fifteen of these DE transcripts
were annotated as pig genes in the GenBank database (DB). Two hundred and seventy
two biological process categories (BP), 75 cellular components and 171 molecular
functions were substantially altered in the TG compared to CG. Many BP were
involved in host immune responses (i.e., signaling, signal transmission, signal
transduction, response to stimulus, oxidation reduction, response to stress,
immune system process, signaling pathway, immune response, cell surface receptor
linked signaling pathway). Seven DE gene pathways (VEGF signaling pathway, Long
term potentiation, Ribosome, Asthma, Allograft rejection, Type I diabetes
mellitus and Cardiac muscle contraction) and statistically significant
associations with host responses were affected. Many cytokines (including NRAS,
PI3K, MAPK14, CaM, HSP27, protein phosphatase 3, catalytic subunit and alpha
isoform), mediating the proliferation and migration of endothelial cells and
promoting survival and vascular permeability, were activated in TG, whilst many
immunomodulatory cytokines were suppressed. The significant changes in the
expression patterns of the genes, GO terms, and pathways, led to a decrease of
antigenic peptides with antigen presenting cells presented to T lymphocytes via
the major histocompatibility complex, and alleviated immune response induced APP
of HN. The immune response ability of HN in the APP-infected pigs was weakened;
however, cell proliferation and migration ability was enhanced.
PMID- 24351864
TI - Thyroid hormones and antioxidant systems: focus on oxidative stress in
cardiovascular and pulmonary diseases.
AB - In previous works we demonstrated an inverse correlation between plasma Coenzyme
Q10 (CoQ10) and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients
were found among the lowest detected in human diseases. On the contrary, CoQ10 is
elevated in hypothyroid subjects, also in subclinical conditions, suggesting the
usefulness of this index in assessing metabolic status in thyroid disorders. A
Low-T3 syndrome is a condition observed in several chronic diseases: it is
considered an adaptation mechanism, where there is a reduction in pro-hormone T4
conversion. Low T3-Syndrome is not usually considered to be corrected with
replacement therapy. We review the role of thyroid hormones in regulation of
antioxidant systems, also presenting data on total antioxidant capacity and
Coenzyme Q10. Published studies suggest that oxidative stress could be involved
in the clinical course of different heart diseases; our data could support the
rationale of replacement therapy in low-T3 conditions.
PMID- 24351865
TI - Rheumatoid arthritis-associated microRNA-155 targets SOCS1 and upregulates TNF
alpha and IL-1beta in PBMCs.
AB - miR-155 plays a crucial role in proinflammatory activation. This study was
carried out to assess the association of abnormal expression of miR-155 in
peripheral blood of patients with Rheumatoid arthritis with the expression of TNF
alpha and IL-1beta. Release of TNF-alpha and IL-1beta, and expression of miR-155
were determined in RA peripheral blood or peripheral blood macrophages, followed
by correlation analysis of the cytokines release and miR-155 expression.
Furthermore, in vitro studies indicate that miR-155 inhibited the expression of
SOCS1. Our results suggest that there is a correlation between the high-level
expression of miR-155 and the enhanced expression of TNF-alpha and IL-1beta. miR
155 targets and suppresses the expression of SOCS1, and the decrease of SOCS1 may
lead to the upregulation of TNF-alpha and IL-1beta.
PMID- 24351867
TI - One step synthesis of NiO nanoparticles via solid-state thermal decomposition at
low-temperature of novel aqua(2,9-dimethyl-1,10-phenanthroline)NiCl2 complex.
AB - [NiCl2(C14H12N2)(H2O)] complex has been synthesized from nickel chloride
hexahydrate (NiCl2.6H2O) and 2,9-dimethyl-1,10-phenanthroline (dmphen) as N,N
bidentate ligand. The synthesized complex was characterized by elemental
analysis, infrared (IR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy
and differential thermal/thermogravimetric analysis (TG/DTA). The complex was
further confirmed by single crystal X-ray diffraction (XRD) as triclinic with
space group P-1. The desired complex, subjected to thermal decomposition at low
temperature of 400 degrees C in an open atmosphere, revealed a novel and facile
synthesis of pure NiO nanoparticles with uniform spherical particle; the
structure of the NiO nanoparticles product was elucidated on the basis of Fourier
transform infrared (FT-IR), UV-vis spectroscopy, TG/DTA, XRD, scanning electron
microscopy (SEM), energy-dispersive X-ray spectrometry (EDXS) and transmission
electron microscopy (TEM).
PMID- 24351866
TI - Visual detection and evaluation of latent and lytic gene expression during
Epstein-Barr virus infection using one-step reverse transcription loop-mediated
isothermal amplification.
AB - Epstein-Barr virus (EBV)-associated disease exhibits distinct gene expression
patterns characterized by the transcription of EBV nuclear antigen (EBNA) 1,
EBNA2, latent membrane protein (LMP) 1, LMP2A, and BZLF1 (Zebra). A series of
visual reverse transcript loop-mediated isothermal amplification (RT-LAMP) assays
were performed to examine the expression of EBNA1, EBNA2, LMP1, LMP2A and BZLF1.
The sensitivity of RT-LAMP for these transcripts was approximately equivalent to
real-time RT-PCR (RT-qPCR), which was developed to quantify relative levels of
EBV transcripts, and 10 to 100-fold more sensitive than conventional RT-PCR.
Cross-reactions to other viruses were not observed upon examination of cell lines
infected with herpes simplex viruses-1 and -2 (HSV-1 and -2), varicella zoster
virus (VZV), human cytomegalovirus (HCMV) or Kaposi's sarcoma-associated
herpesvirus. When applied to 146 specimens, RT-LAMP exhibited high clinical
sensitivity and specificity, with an excellent agreement (kappa > 0.92) compared
to RT-qPCR. These assays are convenient for rapid early diagnosis and for
surveillance of EBV-infected individuals by evaluating the EBV transcriptional
profile, because the results can be visualized with the naked eye. These assays
may be employed in further investigations because they can aid the design of
improved therapeutic regimens and can be used specifically in resource-poor
settings.
PMID- 24351868
TI - Analysis of the binding sites of porcine sialoadhesin receptor with PRRSV.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) can infect pigs and
cause enormous economic losses to the pig industry worldwide. Porcine
sialoadhesin (pSN) and CD163 have been identified as key viral receptors on
porcine alveolar macrophages (PAM), a main target cell infected by PRRSV. In this
study, the protein structures of amino acids 1-119 from the pSN and cSN (cattle
sialoadhesin) N-termini (excluding the 19-amino acid signal peptide) were modeled
via homology modeling based on mSN (mouse sialoadhesin) template structures using
bioinformatics tools. Subsequently, pSN and cSN homology structures were
superposed onto the mSN protein structure to predict the binding sites of pSN. As
a validation experiment, the SN N-terminus (including the wild-type and site
directed-mutant-types of pSN and cSN) was cloned and expressed as a SN-GFP
chimera protein. The binding activity between SN and PRRSV was confirmed by WB
(Western blotting), FAR-WB (far Western blotting), ELISA (enzyme-linked
immunosorbent assay) and immunofluorescence assay. We found that the S107 amino
acid residue in the pSN N-terminal played a crucial role in forming a special
cavity, as well as a hydrogen bond for enhancing PRRSV binding during PRRSV
infection. S107 may be glycosylated during PRRSV infection and may also be
involved in forming the cavity for binding PRRSV along with other sites,
including W2, Y44, S45, R97, R105, W106 and V109. Additionally, S107 might also
be important for pSN binding with PRRSV. However, the function of these binding
sites must be confirmed by further studies.
PMID- 24351869
TI - Anti-inflammatory effects of 4-methylcyclopentadecanone on edema models in mice.
AB - The present study evaluated the anti-inflammatory effects of 4
methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine
the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was
evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and
5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory
activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced
mouse paw edema. The animals were treated with 4-MCPC once every day for seven
consecutive days. Edema index, % inhibition, IL-1beta, TNF-alpha, PGE2 and MPO
levels in paws were detected after the treatment with xylene or carrageenan. Our
results indicated that the LD50 value of 4-MCPC in rats is greater than 5000
mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg.
4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema.
Further study revealed that 4-MCPC treatment also decreased IL-1beta, TNF-alpha,
PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited
more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg.
Taken together, our results suggest that 4-MCPC has potent anti-inflammatory
activity and the mechanisms might be related to the decreases of the levels of IL
1beta, TNF-alpha, PGE2 and MPO in inflamed paws.
PMID- 24351870
TI - Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with
tacrolimus pharmacokinetics in liver transplant patients.
AB - Tacrolimus is a widely used immunosuppressant after organ transplantation. The
narrow therapeutic window and individual variability in tacrolimus
pharmacokinetics make management of this agent a great challenge. This study was
undertaken to determine the association of clinical markers, cytochrome P450,
family 3, subfamily A, polypeptide 5 (CYP3A5) and nuclear receptor subfamily 1,
group I, member 3 (NR1I3) gene polymorphisms with tacrolimus pharmacokinetics. A
total of 96 liver transplant patients were enrolled in the study. Tacrolimus dose
adjusted trough concentration (C/D ratio) and clinical markers were recorded for
one month after transplantation. CYP3A5 and NR1I3 gene polymorphisms for both
donor and recipient were genotyped. In single variable analysis, hemoglobin (Hb),
hematocrit (Hct), donor CYP3A5, NR1I3 gene polymorphisms and recipient CYP3A5
gene polymorphisms were associated with log-transformed tacrolimus C/D ratios.
Hb, donor CYP3A5, NR1I3 gene polymorphisms and recipient CYP3A5 gene
polymorphisms showed association with log-transformed tacrolimus C/D ratios in
the final multiple linear regression model. Donor CYP3A5 polymorphisms were the
most important variant, accounting for 14.3% of total variation involved in
tacrolimus pharmacokinetics. This information could be useful in developing
individualized tacrolimus treatment after liver transplantation.
PMID- 24351871
TI - Optimization of mycophenolic acid therapy using clinical pharmacometrics.
AB - Novel approaches applying quantitative clinical pharmacology or pharmacometrics
have been increasingly embraced by the drug development community in the last
decade. State-of-the-art population modeling and simulation enable better
characterization and prediction of drug exposure. For narrow therapeutic index
drugs such as mycophenolic acid (MPA) which exhibit large inter-individual
variation in drug exposure, pharmacometric analysis can be of great clinical
benefit. This review aims to summarize the recent progress of using
pharmacometric tools toward individualized MPA therapeutics. The population
pharmacokinetic models including those developed for special populations and
Bayesian estimators for therapeutic drug management will be reviewed. Special
attention will be given to new methodologies such as nonparametric population
modeling and the physiological-based pharmacokinetics modeling (PBPK) that
emerged recently as alternatives to the parametric population approach to predict
MPA exposure. D-Optimal design strategies applied in clinical study design will
also be reviewed. Lastly, the potential of using a pharmacodynamic based optimal
treatment strategy by focusing on MPA's target enzyme inosine monophosphate
dehydrogenase (IMPDH) will be discussed.
PMID- 24351872
TI - A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in
rats.
AB - A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized
(HDS) kerosene, a test material that also met the commercial specifications for
aviation turbine fuel (jet A). The objectives were to assess the potential for
target organ toxicity and neurotoxicity. The HDS kerosene was applied to the
shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0
(vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or
495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the
high-dose groups were held without treatment for 4 weeks to assess recovery.
Standard parameters of toxicity were investigated during the in-life phase. At
necropsy, organs were weighed and selected tissues were processed for microscopic
evaluation. Neurobehavioral evaluations included tests of motor activity and
functional observations that were conducted pretest, at intervals during the
exposure period and after recovery. No test substance-related effects on
mortality, clinical observations (except dermal irritation), body weight, or
clinical chemistry values were observed. A dose-related increase in skin
irritation, confirmed histologically as minimal, was evident at the dosing site.
The only statistically significant change considered potentially treatment
related was an increase in the neutrophil count in females at 13 weeks. No test
article-related effects were observed in the neurobehavioral assessments or gross
or microscopic findings in the peripheral or central nervous system tissues in
any of the dose groups. Excluding skin irritation, the no observed adverse effect
level value for all effects was considered 495 mg/kg/d.
PMID- 24351873
TI - The mammalian toxicological hazards of petroleum-derived substances: an overview
of the petroleum industry response to the high production volume challenge
program.
AB - Petroleum-derived substances are complex and composed of aliphatic (normal-, iso
, and cycloparaffins), olefinic, and/or aromatic constituents. Approximately 400
of these complex substances were evaluated as part of the US Environmental
Protection Agency voluntary High Production Volume (HPV) Challenge program. The
substances were separated into 13 groups (categories), and all available data
were assessed. Toxicology testing was conducted as necessary to fully address the
end points encompassed by the HPV initiative. In a broad sense, volatile
hydrocarbons may cause acute central nervous system effects, and those that are
liquids at room temperature pose aspiration hazards if taken into the lungs as
liquids and may also cause skin irritation. Higher boiling substances may contain
polycyclic aromatic constituents (PACs) that can be mutagenic and carcinogenic
and may also cause developmental effects. Substances containing PACs can also
cause target organ and developmental effects. The effects of aliphatic
constituents include liver enlargement and/or renal effects in male rats via an
alpha-2u-globulin-mediated process and, in some cases, small but statistically
significant reductions in hematological parameters. Crude oils may contain other
constituents, particularly sulfur- and nitrogen-containing compounds, which are
removed during refining. Aside from these more generic considerations, some
specific petroleum substances may contain unusually toxic constituents including
benzene, 1,3-butadiene, and/or n-hexane, which should also be taken into account
if present at toxicologically relevant levels.
PMID- 24351874
TI - Algodystrophy in children and adolescents: a review.
AB - Algodystrophy occurs in children significantly less frequently than in adults.
Symptomatology, course, responsiveness to treatment and prognosis of the
pediatric disease is also different from the "adult" form. This paper presents
substantial peculiarities of pediatric algodystrophy: it occurs after relatively
minor trauma, involves lower limb more frequently than upper limb and presents
with pain, paleness and coldness of the skin in the affected part, as well as
with serious functional impairment. Diagnosis of the condition is based on
clinical grounds and no imaging is necessary to confirm the diagnosis.
Psychological distress is suspected in the development of the disease in children
and adolescents, but there is no definitive evidence supporting this view.
Treatment of pediatric algodystrophy should be complex and consist of physical
therapy, psychotherapy, pain therapy and, in selected cases, sympathetic and
somatic blocks. The literature emphasizes very poor knowledge of algodystrophy in
the pediatric community.
PMID- 24351875
TI - Pregnancy and Glycemic Index Outcomes study: effects of low glycemic index
compared with conventional dietary advice on selected pregnancy outcomes.
AB - BACKGROUND: Eating carbohydrate foods with a high glycemic index (GI) has been
postulated to result in fetoplacental overgrowth and higher infant body fat. A
diet with a low glycemic index (LGI) has been shown to reduce birth percentiles
and the ponderal index (PI). OBJECTIVES: We investigated whether offering LGI
dietary advice at the first antenatal visit would result in a lower fetal birth
weight, birth percentile, and PI than providing healthy eating (HE) advice. This
advice had to be presented within the resources of routine antenatal care.
DESIGN: The Pregnancy and Glycemic Index Outcomes study was a 2-arm, parallel
design, randomized, controlled trial that compared the effects of LGI dietary
advice with HE advice on pregnancy outcomes. Eligible volunteers who attended for
routine antenatal care at <20 wk of gestation were randomly assigned to either
group. RESULTS: A total of 691 women were enrolled, and 576 women had final data
considered. In the LGI group, the GI was reduced from a mean (+/- SEM) of 56 +/-
0.3 at enrollment to 52 +/- 0.3 (P < 0.001) at the final assessment. There were
no significant differences in primary outcomes of fetal birth weight, birth
percentile, or PI. In a multivariate regression analysis, the glycemic load was
the only significant dietary predictor (P = 0.046) of primary outcomes but
explained <1% of all variation. CONCLUSION: A low-intensity dietary intervention
with an LGI diet compared with an HE diet in pregnancy did not result in any
significant differences in birth weight, fetal percentile, or PI.
PMID- 24351876
TI - A randomized trial on the effects of flavorings on the health benefits of daily
peanut consumption.
AB - BACKGROUND: Chronic peanut consumption is associated with health benefits. To
encourage consumption, peanuts are marketed with various flavorings, but
questions have been raised as to whether seasonings offset the benefits of
peanuts alone. OBJECTIVE: This study sought to determine whether flavorings on
peanuts affect health benefits over 12 wk. DESIGN: In a randomized, parallel
group trial, 151 participants received 42 g peanuts/d as 14-g servings of 3
different flavors (n = 50) or a single flavor (n = 25-26/group). Anthropometric
indexes, blood pressure, and heart rate were measured biweekly. Cardiovascular
disease risk factors (serum lipids, insulin, glucose, and cortisol) were assessed
monthly. RESULTS: No single added flavor differentially altered body weight, body
fat, body mass index, heart rate, or blood indexes in the total sample.
Participants at greater risk of cardiovascular disease had significantly greater
mean (+/- SE) reductions in diastolic blood pressure (-5.0 +/- 1.7 mm Hg compared
with -0.7 +/- 0.6 mm Hg), cholesterol (-12.1 +/- 8.5 mg/dL compared with +5.6 +/-
2.0 mg/dL), and triglycerides (-31.7 +/- 15.8 mg/dL compared with +2.3 +/- 3.0
mg/dL) (n = 27, 24, and 15, respectively; P < 0.01) than did those at lower risk,
who did not have significantly different cholesterol or triglyceride
concentrations. Consumption of a variety of flavors led to greater weight gain
(0.9 +/- 0.3 kg) compared with individual flavors alone (0.5 +/- 0.2 kg) (P <
0.05), but increases in fat and lean masses were not significant. CONCLUSIONS:
Regardless of flavoring, peanut consumption offered significant benefits to
participants with elevated serum lipids and blood pressure. Sensory variety led
to a small, but significant, increase in body weight in comparison with ingestion
of a single flavor but no change in fat mass.
PMID- 24351877
TI - Mediterranean and Dietary Approaches to Stop Hypertension dietary patterns and
risk of sudden cardiac death in postmenopausal women.
AB - BACKGROUND: The Mediterranean and Dietary Approaches to Stop Hypertension (DASH)
diets are characterized by higher intake of fruit, vegetables, whole grains, and
unsaturated fatty acids. All of these foods and nutrients may affect cholesterol,
inflammation, the development of atherosclerosis, and, therefore, risk of cardiac
death. OBJECTIVE: Our objective was to examine the association between the
Mediterranean and DASH dietary patterns and risk of sudden cardiac death (SCD) in
women. DESIGN: We used a prospective cohort of 93,122 postmenopausal women
enrolled in the Women's Health Initiative study between 1993 and 1998 and
followed for an average of 10.5 y. Women completed a food-frequency questionnaire
(FFQ) twice during follow-up. We scored their diets according to how closely the
reported diet resembled each dietary pattern. SCD was defined as death that
occurred within 1 h of symptom onset. RESULTS: A higher Mediterranean diet score
was associated with lower risk of SCD (HR: 0.64; 95% CI: 0.43, 0.94) when women
in the highest quintile were compared with women in the lowest quintile after
adjustment for age, total energy, race, income, smoking, and physical activity.
After adjustment for potential mediators, the association was similar (HR: 0.67;
95% CI: 0.46, 0.99). A higher DASH diet score was not associated with risk of
SCD. However, sodium intake, which is a crucial component of the DASH dietary
pattern, was not well characterized by the FFQ. CONCLUSION: The Mediterranean
dietary pattern may be associated with lower risk of SCD in women. This trial was
registered at clinicaltrials.gov as NCT00000611.
PMID- 24351878
TI - Low-calorie- and calorie-sweetened beverages: diet quality, food intake, and
purchase patterns of US household consumers.
AB - BACKGROUND: Few studies have investigated the diet quality of consumers of low
calorie-sweetened (LCS) and calorie-sweetened (CS) beverages. OBJECTIVE: The
objective was to examine the dietary quality and adherence to dietary purchasing
and consumption patterns of beverage consumers from 2000 to 2010. DESIGN: We
analyzed purchases for 140,352 households from the Homescan longitudinal data set
2000-2010 and dietary intake from NHANES 2003-2010 (n = 34,393). We defined
mutually exclusive consumer profiles as main exposures: LCS beverages, CS
beverages, LCS & CS beverages, and non/low consumers. As main outcomes, we
explored dietary quality by using total energy and macronutrients (kcal/d). We
performed factor analyses and applied factor scores to derive dietary patterns as
secondary outcomes. Using multivariable linear (NHANES) and random-effects
(Homescan) models, we investigated the associations between beverage profiles and
dietary patterns. RESULTS: We found "prudent" and "breakfast" patterns in
Homescan and NHANES, "ready-to-eat meals/fast-food" and "prudent/snacks/LCS
desserts" patterns in Homescan, and "protein/potatoes" and "CS
desserts/sweeteners" patterns in NHANES. In both data sets, compared with non/low
consumers, both CS- and LCS-beverage consumers had a significantly higher total
energy from foods, higher energy from total and SFAs, and lower probability of
adherence to prudent and breakfast patterns. In Homescan, LCS-beverage consumers
had a higher probability of adherence to 2 distinct patterns: a
prudent/snacks/LCS dessert pattern and a ready-to-eat meals/fast-food purchasing
pattern. CONCLUSIONS: Our findings suggest that overall dietary quality is lower
in LCS-, CS-, and LCS & CS-beverage consumers relative to non/low consumers. Our
study highlights the importance of targeting foods that are linked with sweetened
beverages (either LCS or CS) in intervention and policy efforts that aim to
improve nutrition in the United States.
PMID- 24351879
TI - Preclinical evaluation of parametric image reconstruction of [18F]FMISO PET:
correlation with ex vivo immunohistochemistry.
AB - Compared to indirect methods, direct parametric image reconstruction (PIR) has
the advantage of high quality and low statistical errors. However, it is not yet
clear if this improvement in quality is beneficial for physiological
quantification. This study aimed to evaluate direct PIR for the quantification of
tumor hypoxia using the hypoxic fraction (HF) assessed from immunohistological
data as a physiological reference. Sixteen mice with xenografted human squamous
cell carcinomas were scanned with dynamic [18F]FMISO PET. Afterward, tumors were
sliced and stained with H&E and the hypoxia marker pimonidazole. The hypoxic
signal was segmented using k-means clustering and HF was specified as the ratio
of the hypoxic area over the viable tumor area. The parametric Patlak slope
images were obtained by indirect voxel-wise modeling on reconstructed images
using filtered back projection and ordered-subset expectation maximization (OSEM)
and by direct PIR (e.g., parametric-OSEM, POSEM). The mean and maximum Patlak
slopes of the tumor area were investigated and compared with HF. POSEM resulted
in generally higher correlations between slope and HF among the investigated
methods. A strategy for the delineation of the hypoxic tumor volume based on
thresholding parametric images at half maximum of the slope is recommended based
on the results of this study.
PMID- 24351880
TI - Factors associated with symptom-specific psychological and functional impact
among acoustic neuroma patients.
AB - INTRODUCTION: The main purpose of this study was to investigate the psychological
and functional impact attributed to acoustic neuroma symptoms. MATERIALS AND
METHODS: A sample of 207 acoustic neuroma patients completed a study-specific
questionnaire about the severity, frequency, and psychological and functional
impact of 9 acoustic neuroma symptoms. RESULTS: The survey response rate was 56.4
per cent. All symptoms had some degree of psychological impact for the majority
of participants; hearing loss was the symptom most often reported to have a
severe psychological impact. The majority of respondents reported functional
impact attributed to hearing loss, balance disturbance, dizziness, eye problems,
headache and fatigue; balance disturbance was the symptom most often reported to
have a severe functional impact. For most symptoms, psychological and functional
impact were related to severity and frequency. CONCLUSION: Of the acoustic
neuroma symptoms investigated, hearing loss and balance disturbance were the most
likely to have a severe psychological and functional impact, respectively.
PMID- 24351881
TI - A prospective survey in European Society of Cardiology member countries of atrial
fibrillation management: baseline results of EURObservational Research Programme
Atrial Fibrillation (EORP-AF) Pilot General Registry.
AB - AIMS: Given the advances in atrial fibrillation (AF) management and the
availability of new European Society of Cardiology (ESC) guidelines, there is a
need for the systematic collection of contemporary data regarding the management
and treatment of AF in ESC member countries. METHODS AND RESULTS: We conducted a
registry of consecutive in- and outpatients with AF presenting to cardiologists
in nine participating ESC countries. All patients with an ECG-documented
diagnosis of AF confirmed in the year prior to enrolment were eligible. We
enroled a total of 3119 patients from February 2012 to March 2013, with full data
on clinical subtype available for 3049 patients (40.4% female; mean age 68.8
years). Common comorbidities were hypertension, coronary disease, and heart
failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was
common, particularly among those with permanent AF. Amiodarone was the most
common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the
most used rate control drugs. Oral anticoagulants (OACs) were used in 80%
overall, most often vitamin K antagonists (71.6%), with novel OACs being used in
8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin)
were still used in one-third of the patients, and no antithrombotic treatment in
only 4.8%. Oral anticoagulants were used in 56.4% of CHA2DS2-VASc = 0, with 26.3%
having no antithrombotic therapy. A high HAS-BLED score was not used to exclude
OAC use, but there was a trend towards more aspirin use in the presence of a high
HAS-BLED score. CONCLUSION: The EURObservational Research Programme Atrial
Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of
contemporary data regarding the management and treatment of AF by cardiologists
in ESC member countries. Oral anticoagulant use has increased, but novel OAC use
was still low. Compliance with the treatment guidelines for patients with the
lowest and higher stroke risk scores remains suboptimal.
PMID- 24351883
TI - Complication due to entrapment in the Chiari apparatus.
PMID- 24351882
TI - Real-time assessment of pulmonary vein disconnection during cryoablation of
atrial fibrillation: can it be 'achieved' in almost all cases?
AB - AIM: Real-time assessment of pulmonary vein (PV) disconnection is possible using
an inner circular mapping catheter during cryoablation of atrial fibrillation
(AF). However, it has been recently demonstrated that such continuous monitoring
may only be possible in <50% of PVs. We hypothesized that a stepwise mapping
approach, including pacing manoeuvres, could optimize monitoring of real-time PV
disconnection during ablation. METHODS AND RESULTS: Single-centre, prospective
observational study (NCT01843465) including 34 consecutive eligible patients (128
PVs) undergoing a first procedure of cryoballoon ablation of AF using the Artic
Front Advance((r)) 28 mm catheter and a 20 mm diameter Achieve((r)) catheter (AC)
in all cases. Monitoring of real-time entrance block was possible, when AC was
maintained in the standard position (distal to the tip of the Artic Front
Advance((r)) catheter) in 47 (36.7%) PVs. In an additional 63 cases (49.2%), such
monitoring was possible after moving AC to a more proximal position and using
different torqueing movements. Finally, using supplemental systematic pacing
manoeuvres to test exit block, real-time assessment of PV disconnection was
possible in 15 (11.7%) more PVs. Overall, real-time assessment of PV
disconnection was possible in 97.7% of cases, after a mean duration of 48.6 +/-
33.0 s. CONCLUSION: Our results suggest that optimal use of the AC, with a
systematic stepwise mapping approach, may dramatically improve the real-time
monitoring of PV disconnection during AF cryoablation.
PMID- 24351884
TI - How many patients fulfil the surface electrocardiogram criteria for subcutaneous
implantable cardioverter-defibrillator implantation?
AB - AIMS: To determine the number of patients with a primary or secondary prevention
implantable cardioverter-defibrillator (ICD) indication who are eligible for
subcutaneous ICD (S-ICD) implantation according to the S-ICD manufacturer's
surface electrocardiogram (ECG) screening template. METHODS AND RESULTS: One
hundred and ninety-six ICD patients with a non-paced ventricle were assessed
using erect and supine ECG limb lead recordings to simulate the three S-ICD
sensing vectors. Each ECG lead was scrutinized by two independent observers.
Subcutaneous ICD eligibility required two or more leads to satisfy the S-ICD
screening template in both erect and supine positions. Overall, 85.2% of patients
[95% confidence interval (CI): 80.2-90.2%] fulfilled surface ECG screening
criteria. The proportion of patients with 3, 2, 1, and 0 qualifying leads were
37.2% (95% CI: 30.4-44.0%), 48.0% (95% CI: 41.0-55.0%), 11.2% (95% CI: 6.8
15.6%), and 3.6% (95% CI: 1.0-6.2%). The S-ICD screening template was satisfied
more often by Lead III (primary vector, 83.7%, 95% CI: 78.5-88.9%) and Lead II
(secondary vector, 82.7%, 95% CI: 77.4-88.0%) compared with Lead I (alternate
vector, 52.6%, 95% CI: 45.6-59.6%). A prolonged QRS duration was the only
baseline characteristic independently associated with ineligibility for S-ICD
implantation. There was 92.9% agreement between the two independent observers in
assessment of eligibility using the S-ICD screening template. CONCLUSION: About
85.2% of patients with an indication for a primary or secondary prevention ICD
have a surface ECG that is suitable for S-ICD implantation when assessed with an
S-ICD screening template. There is minor inter-observer variation in assessment
of eligibility using the S-ICD screening template.
PMID- 24351885
TI - Depression in paroxysmal and persistent atrial fibrillation patients: a cross
sectional comparison of patients enroled in two large clinical trials.
AB - AIMS: Despite its high clinical relevance, few studies have investigated
depression in patients with atrial fibrillation (AF). We aimed to assess whether
depressed mood was more common in persistent or paroxysmal AF patients in
controlled models and report frequencies of major depressive disorder. METHODS
AND RESULTS: Cross-sectional data from two contemporary clinical trials were used
to compare paroxysmal (n = 310) and persistent (n = 392) AF patients' depressed
mood severity (measured by the Major Depression Inventory) with each trial
including only one patient type. A four-category outcome of depressed mood
severity was chosen as exposure variable. Ordinal logistic regression was applied
to analyse the association of AF type with depressed mood in a crude model and a
confounder control model. In the study sample, 8.4% were classified as having
major depressive disorder [10.5% of persistent and 5.8% of paroxysmal patients;
odds ratio (OR) = 1.89; 95% confidence interval (CI): 1.07-3.37], according to
the diagnostic and statistical manual of mental disorders [(diagnostic and
statistical manual of mental disorders (DSM-IV)] criteria. In both the age and
sex adjusted crude model and in the confounder control model, the association of
persistent AF with more severe depressed mood was significant (OR confounder
controlled model = 1.44; 95% CI: 1.13-1.75, P = 0.007). CONCLUSION: Persistent AF
patients may suffer from more severe depressed mood than paroxysmal AF patients
with similar symptom burden after controlling for relevant factors.
PMID- 24351886
TI - Procedural sedation with dexmedetomidine during ablation of atrial fibrillation:
a randomized controlled trial.
AB - AIMS: Procedural sedation by non-anaesthesiologists with GABAergic anaesthetics
has the potential risk of fatal respiratory depression. Dexmedetomidine works its
sedative action via alpha2-adrenergic receptors, and is less associated with
respiratory depression. We tested the usability of dexmedetomidine as a
procedural sedative during ablation of atrial fibrillation (AF). METHODS AND
RESULTS: Consecutive patients were randomized to be treated with dexmedetomidine
(n = 43) or thiamylal (n = 44) as sedatives during AF ablation. Apnoeic and body
movement events were monitored using a novel portable respiratory monitor, the SD
101, during the procedure. Although the majority of the patients receiving
dexmedetomidine required rescue sedations with thiamylal, the respiratory
disturbance index (RDI) defined as the total number of sleep-disordered breathing
events divided by the recording time (10.4 +/- 5.1 vs. 18.2 +/- 8.1 events/h; P <
0.0001) and movement index defined as the number of body movement events per hour
(7.6 +/- 6.1 vs. 11.0 +/- 5.5 events/h; P = 0.0098) were both significantly lower
in the dexmedetomidine arm than in the thiamylal arm. A multivariate linear
regression analysis including potential factors revealed that dexmedetomidine vs.
thiamylal was solely and independently associated with the RDI (beta = -0.62; P =
0.0031). The occurrence of hypotension [9 (21%) vs. 4 (9%); P = 0.14] and
bradycardia [4 (9%) vs. 4 (9%); P = 1.0] were similar in the patients with
dexmedetomidine and thiamylal. CONCLUSION: Procedural sedation with
dexmedetomidine may assure safety and patient immobility during AF ablation, and
therefore may be a potential alternative for that with GABAergic anaesthetics.
PMID- 24351887
TI - Paranitroanaline poisoning: a failure in basic prevention?
AB - The Occupational Medicine Forum is prepared by the ACOEM Occupational and
Environmental Medical Practice Committee and does not necessarily represent an
official ACOEM position. The Forum is intended for health professionals and is
not intended to provide medical or legal advice, including illness prevention,
diagnosis or treatment, or regulatory compliance. Such advice should be obtained
directly from a physician and/or attorney.
PMID- 24351888
TI - Promoting physical activity and healthy dietary behavior: the role of the
occupational health services: a scoping review.
AB - OBJECTIVE: Conduct a scoping review to identify and map the literature that has
evaluated the effects of health promotion interventions aimed at physical
activity and/or dietary behavior, implemented by the occupational health
services. METHODS: A search for peer-reviewed articles was conducted (up to
February 2013) through electronic databases, hand searching of key journals, and
reference lists. A methodological quality assessment was performed. RESULTS:
Fourteen studies were included, describing 10 interventions. The main component
was counseling of individuals with known cardiovascular disease risk factors.
Intervention effects were reported for dietary behavior, physical activity,
sedentary behavior, and biological risk factors. CONCLUSIONS: Results are
promising, especially with regard to interventions containing counseling
targeting individuals at risk. High-quality studies using objective measures to
assess behavioral outcomes and the (cost)-effectiveness of interventions
containing counseling, PA on prescription, and multilevel interventions are
needed.
PMID- 24351889
TI - Managing implementation: roles of line managers, senior managers, and human
resource professionals in an occupational health intervention.
AB - OBJECTIVE: To contrast line managers', senior managers', and (human resource) HR
professionals' descriptions of their roles, tasks, and possibilities to perform
them during the implementation of an occupational health intervention. METHODS:
Interviews with line managers (n = 13), senior managers (n = 7), and HR
professionals (n = 9) 6 months after initiation of an occupational health
intervention at nine organizations. RESULTS: The groups' roles were described
coherently, except for the HR professionals. These roles were seldom performed in
practice, and two main reasons appeared: use of individuals' engagement rather
than an implementation strategy, and lack of integration of the intervention with
other stakeholders and organizational processes. CONCLUSIONS: Evaluation of
stakeholders' perceptions of each other's and their own roles is important,
especially concerning HR professionals. Clear role descriptions and
implementation strategies, and aligning an intervention to organizational
processes, are crucial for efficient intervention management.
PMID- 24351890
TI - Cross-sectional survey of workers exposed to aliphatic diisocyanates using
detailed respiratory medical history and questions regarding accidental skin and
respiratory exposures.
AB - OBJECTIVES: To identify possible cases of occupational asthma and assess
accidental skin and inhalation exposures to aliphatic diisocyanates. METHODS:
Seventy-three employees from two plants, manufacturing or producing aliphatic
diisocyanates, were surveyed using a detailed respiratory history questionnaire
with additional questions on accidental skin and inhalation exposures. Further
reviews of medical records and interviews were used to determine whether any of
15 employees with questionable responses had developed occupational asthma.
RESULTS: No cases of occupational asthma were identified. Nevertheless, many
employees reported occasional accidental unprotected skin exposures and/or
detecting the odor of 1,6-hexamethylene diisocyanate or isophorone diisocyanate.
CONCLUSIONS: Consistent with a previous study, no cases of occupational asthma
were identified from exposure to 1,6-hexamethylene diisocyanate, isophorone
diisocyanate, methylene bis(4-cyclohexyl isocyanate), or their polyisocyanates
even though many employees reported detection of odors (93%) or skin exposures
(53%).
PMID- 24351891
TI - Job control, psychological demand, and farmworker health: evidence from the
national agricultural workers survey.
AB - OBJECTIVE: Improve understanding of the potential occupational health impact of
how agricultural jobs are organized. Exposure to low job control, high
psychological demands, and high job strain were hypothesized to have greater risk
for poor self-rated physical health and elevated depressive symptoms. METHODS:
Cross-sectional data (N = 3691) obtained using the Work Organization and
Psychosocial Factors module of the US National Agricultural Workers Survey
fielded in 2009-2010. RESULTS: More than one fifth (22.4%) of farmworkers
reported fair/poor health, and 8.7% reported elevated depressive symptoms. High
psychological demand was associated with increased risk of fair/poor health (odds
ratio, 1.73; 95% confidence interval, 1.4 to 2.2) and elevated depressive
symptoms (odds ratio, 2.6; 95% confidence interval, 1.9 to 3.8). CONCLUSIONS: The
organization of work in field agriculture may pose risks for poor occupational
health outcomes among a vulnerable worker population.
PMID- 24351892
TI - Longitudinal determinants of energy levels in knowledge workers.
AB - OBJECTIVE: Increasingly, workers in the service, welfare, and health care sectors
suffer adverse effects (ie, depression, burnout, etc) of "low-energy syndromes."
Less is known about energy-based outcomes among knowledge workers. This study
aimed to identify determinants of self-rated energy in knowledge workers and
examine how these determinants change over time. METHODS: In collaboration with a
large union and employer federation, 317 knowledge workers in Sweden responded to
the health and productivity survey three times. RESULTS: At each assessment,
worry, satisfaction with eating habits, and work-effectiveness were predictive of
energy levels; however, only work-effectiveness covaried with energy over time.
CONCLUSIONS: This study suggests that perceived work-effectiveness is an
important factor in preventing knowledge workers from experiencing "low-energy
syndromes." Lifestyle factors also play a role. Therefore, multifaceted
interventions for increasing energy are needed.
PMID- 24351893
TI - Use of automated external defibrillators in US federal buildings: implementation
of the Federal Occupational Health public access defibrillation program.
AB - OBJECTIVE: Federal Occupational Health (FOH) administers a nationwide public
access defibrillation program in US federal buildings. We describe the use of
automated external defibrillators (AEDs) in federal buildings and evaluate
survival after cardiac arrest. METHODS: Using the FOH database, we examined
reported events in which an AED was brought to a medical emergency in federal
buildings over a 14-year period, from 1999 to 2012. RESULTS: There were 132
events involving an AED, 96 (73%) of which were due to cardiac arrest of cardiac
etiology. Of 54 people who were witnessed to experience a cardiac arrest and
presented with ventricular fibrillation or ventricular tachycardia, 21 (39%)
survived to hospital discharge. CONCLUSIONS: Public access defibrillation, along
with protocols to install, maintain, and deploy AEDs and train first responders,
benefits survival after cardiac arrest in the workplace.
PMID- 24351894
TI - Workers' knowledge and beliefs about cardiometabolic health risk.
AB - OBJECTIVE: Investigate workers' knowledge and beliefs about cardiometabolic risk.
METHODS: A survey on the risks of diabetes, cardiovascular disease, and chronic
kidney disease was disseminated among Dutch construction workers and employees
from the general working population. RESULTS: We had 482 respondents (26.8%)
among construction workers and 738 respondents (65.1%) among the general working
population. Employees showed reasonable basic knowledge, especially about
cardiovascular disease risk factors and risk reduction. Nevertheless, they also
had knowledge gaps (eg, specific dietary intake) and showed misconceptions of
what elevated risk entails. Employees having lower education, being male, and
having lower health literacy demonstrated less adequate knowledge and beliefs.
CONCLUSION: To improve the potential effect of health risk assessments in the
occupational setting, physicians should explain what it means to be at elevated
cardiometabolic risk and target their messages to employee subgroups.
PMID- 24351895
TI - Cross-sectional study on respiratory morbidity in workers after exposure to
synthetic amorphous silica at five German production plants: exposure assessment
and exposure estimates.
AB - OBJECTIVES: Synthetic amorphous silicas (SASs) are nanostructured polymorphs of
silicon dioxide. We compared two different exposure assessments. METHODS: This
study estimated cumulative exposure to inhalable SAS dust in 484 male workers
from five German SAS-producing plants. Two procedures (P1 and P2) were applied.
P1 was based on an expert assessment. P2 was a multiple exposure assessment (15
scenarios) anchored by a recent measurement series (1375 personal measurements of
inhalable SAS dust concentration) and used expert assessments. RESULTS:
Cumulative exposure estimates for P1 averaged 56.9 mg/m.yrs (range, 0.1 to 419);
for a selected P2 scenario, the mean was 31.8 mg/m.yrs (range, 0.4 to 480), (P <
0.0001). Averages varied between the 15 P2-scenarios from 12.6 to 109.6 mg/m.yrs.
Different time trends for SAS concentrations were observed. CONCLUSIONS: Both
approaches suffer from considerable uncertainties that need to be considered in
epidemiological studies.
PMID- 24351896
TI - The impact of reduced dust exposure on respiratory health among cement workers:
an ecological study.
AB - OBJECTIVES: To compare total dust exposure, prevalence of chronic respiratory
symptoms, lung function, and chronic obstructive pulmonary disease (COPD) among
Tanzanian cement workers before (2002) and after (2010-2011) establishment of
dust-control measures. METHODS: Personal total dust-exposure measurements,
questionnaire assessment for chronic respiratory symptoms, and spirometry were
conducted in both examination periods. RESULTS: Total dust exposure was lower in
2010-2011 than in 2002. The prevalence of most chronic respiratory symptoms and
COPD was lower in 2010 than in 2002. Forced expiratory volume in 1 second (FEV1),
percentage predicted FEV1, and percentage predicted forced vital capacity were
higher among cement workers in 2010 than in 2002. CONCLUSIONS: There was reduced
total dust exposure level, lower prevalence of chronic respiratory symptoms and
COPD, and higher lung function among cement workers in 2010 than in 2002.
PMID- 24351897
TI - Mesothelioma in occupational cohort studies: methodological considerations.
AB - OBJECTIVE: This article describes effective strategies for the identification and
valid assessment of mortality due to mesothelioma. METHODS: We manually reviewed
all death certificates for mention of mesothelioma for all International
Classification of Diseases (ICD) revisions. We tested the accuracy of our
ascertainment method by comparing New Jersey death certificate data from our
health status registry with histologically confirmed cases from the New Jersey
State Cancer Registry. RESULTS: We found reasonably good agreement between death
certificate diagnoses and histologically confirmed cases, kappa coefficient 0.86
(95% confidence interval, 0.76 to 0.95). Most mesothelioma deaths in our test and
North American cohorts were coded to unspecified anatomical sites. CONCLUSIONS:
Limiting ascertainment to pleura and peritoneum ICD codes underestimates
mesothelioma deaths. Reviewing all ICD codes that could contain mesothelioma is
the only effective method for complete capture of mesothelioma diagnoses.
PMID- 24351898
TI - Occupational asbestos exposure and risk of pleural mesothelioma, lung cancer, and
laryngeal cancer in the prospective Netherlands cohort study.
AB - OBJECTIVE: To study the association between occupational asbestos exposure and
pleural mesothelioma, lung cancer, and laryngeal cancer, specifically addressing
risk associated with the lower end of the exposure distribution, risk of cancer
subtypes, and the interaction between asbestos and smoking. METHODS: Using the
Netherlands Cohort Study (n = 58,279 men, aged 55 to 69 years), asbestos exposure
was estimated by linkage to job-exposure matrices. After 17.3 years of follow-up,
132 pleural mesothelioma, 2324 lung cancer, and 166 laryngeal cancer cases were
available. RESULTS: The multivariable-adjusted model showed overall positive
associations between all levels of asbestos exposure and mesothelioma, lung
cancer, and laryngeal cancer. Lung adenocarcinoma and glottis cancer showed only
a positive association after prolonged higher asbestos exposure (hazard ratio per
10 years increment, 1.43 [95% confidence interval, 1.06 to 1.93] and 1.95 [95%
confidence interval, 1.36 to 2.80], respectively). There was no statistically
significant interaction between asbestos and smoking. CONCLUSIONS: Asbestos
levels encountered at the lower end of the exposure distribution may be
associated with an increased risk of pleural mesothelioma, lung cancer, and
laryngeal cancer.
PMID- 24351899
TI - Sick leave days and costs associated with overweight and obesity in Germany.
AB - OBJECTIVE: To analyze the impact of body mass index on sick leave days and
related costs in Germany. METHODS: Cross-sectional analysis of German Socio
Economic Panel data (n = 7990). The relationship between body mass index class
and sick leave days was analyzed via analyses of variance (ANOVA) (bivariate) and
zero-inflated negative binomial regression models (multivariate). RESULTS: Body
mass index was positively associated with annual sick leave days in the bivariate
analysis (P < 0.001). In the fully adjusted zero-inflated negative binomial,
overweight women had 3.64, obese women 5.19, and obese men 3.48 excess sick leave
days in 2009 (vs normal weight), while excess sick leave days of overweight men
were not statistically significant. The extrapolated excess costs in the German
working population amount to &OV0556;2.18 billion (base case). CONCLUSIONS: The
absenteeism-related lost productivity costs associated with excess weight are
formidable and emphasize the persistent need for health promotion efforts in
Germany.
PMID- 24351900
TI - Relationship between poor decision-making process and fatigue perception in
Parkinson's disease patients.
AB - BACKGROUND: Fatigue is a common non-motor symptom in Parkinson's disease
patients. The reasons for its perception are not completely understood. One
suggested possibility might be that perceived fatigue is related with abnormal
interpretation of somatic symptoms. It has been described that somatic markers
misinterpretation leads to poor decision-making. We hypothesized that fatigued
Parkinson's disease patients would show poorer performance than non-fatigued in a
decision-making task. METHODS: To test our hypothesis, 89 Parkinson's disease
patients were assessed for the presence of fatigue using the Parkinson Fatigue
Scale. All patients were also administered scales evaluating psychopathology and
neuropsychological tests, including the Iowa Gambling Task. RESULTS: 33 (37.1%)
patients fulfilled the established criteria for fatigue. In the univariate
analysis, fatigued patients showed higher levels of anxiety (state: p = 0.001,
trait: p < 0.001), impulsivity (p = 0.051), and depression (p < 0.001) than non
fatigued patients. No statistically significant differences in other
neuropsychological test results (Stroop, Trail Making Test, Tower of London) were
found between fatigued and non-fatigued patients except for the Iowa Gambling
Task, in which fatigued patients showed poorer performance (p = 0.001) after
controlling for confounding factors. CONCLUSIONS: These results suggest that
fatigued Parkinson's disease patients may present abnormal decision-making
process, which may reflect abnormal processing of somatic markers when faced with
an activity that requires effort.
PMID- 24351903
TI - Screening mangrove endophytic fungi for antimalarial natural products.
AB - We conducted a screening campaign to investigate fungi as a source for new
antimalarial compounds. A subset of our fungal collection comprising Chinese
mangrove endophytes provided over 5000 lipophilic extracts. We developed an
accelerated discovery program based on small-scale cultivation for crude extract
screening and a high-throughput malaria assay. Criteria for hits were developed
and high priority hits were subjected to scale-up cultivation. Extracts from
large scale cultivation were fractionated and these fractions subjected to both
in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to
purification were developed, including the introduction of a selectivity index
and by dereplication of known metabolites. From the Chinese mangrove endophytes,
four new compounds (14-16, 18) were isolated including a new dimeric
tetrahydroxanthone, dicerandrol D (14), which was found to display the most
favorable bioactivity profile.
PMID- 24351902
TI - Association of marijuana smoking with oropharyngeal and oral tongue cancers:
pooled analysis from the INHANCE consortium.
AB - BACKGROUND: The incidence of oropharyngeal and oral tongue cancers has increased
over the last 20 years which parallels increased use of marijuana among
individuals born after 1950. METHODS: A pooled analysis was conducted comprising
individual-level data from nine case-control studies from the United States and
Latin America in the INHANCE consortium. Self-reported information on marijuana
smoking, demographic, and behavioral factors was obtained from 1,921
oropharyngeal cases, 356 oral tongue cases, and 7,639 controls. RESULTS: Compared
with never marijuana smokers, ever marijuana smokers had an elevated risk of
oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47]
and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The
risk of oropharyngeal cancer remained elevated among never tobacco and alcohol
users. The risk of oral tongue cancer was reduced among never users of tobacco
and alcohol. Sensitivity analysis adjusting for potential confounding by HPV
exposure attenuated the association of marijuana use with oropharyngeal cancer
(aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer
association. CONCLUSIONS: These results suggest that the association of marijuana
use with head and neck carcinoma may differ by tumor site. IMPACT: The
associations of marijuana use with oropharyngeal and oral tongue cancer are
consistent with both possible pro- and anticarcinogenic effects of cannabinoids.
Additional work is needed to rule out various sources of bias, including residual
confounding by HPV infection and misclassification of marijuana exposure.
PMID- 24351904
TI - Identification of four new agr quorum sensing-interfering cyclodepsipeptides from
a marine Photobacterium.
AB - During our search for new natural products from the marine environment, we
discovered a wide range of cyclic peptides from a marine Photobacterium, closely
related to P. halotolerans. The chemical fingerprint of the bacterium showed
primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the
known pyrrothine antibiotic holomycin and a wide range of peptides, from
diketopiperazines to cyclodepsipeptides of 500-900 Da. Purification of components
from the pellet fraction led to the isolation and structure elucidation of four
new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins
interfered with expression of virulence genes known to be controlled by the agr
quorum sensing system of Staphylococcus aureus, although to a lesser extent than
the previously described solonamides from the same strain of Photobacterium.
PMID- 24351905
TI - Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces
apoptosis in MCF-7 breast cancer cells.
AB - Recently, much attention has been given to discovering natural compounds as
potent anti-cancer candidates. In the present study, the anti-cancer effects of
fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus,
was evaluated in vitro. In order to investigate the impact of fumigaclavine C on
inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7
cells were treated with various concentrations of fumigaclavine C, and
fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti
proliferation was analyzed via cell mobility and mitogen-activated protein kinase
(MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition
on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were
manifested in Western blot and reverse transcription polymerase chain reaction
(RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was
studied by analyzing the expression of apoptosis related proteins, cell cycle
analysis, DNA fragmentation and molecular docking studies. It was found that
fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by
modulating the apoptotic protein expressions. Moreover, fumigaclavine C
significantly down-regulated the NF-kappa-B cell survival pathway. Collectively,
data suggest that fumigaclavine C has a potential to be developed as a
therapeutic candidate for breast cancer.
PMID- 24351907
TI - Activation of the nuclear factor E2-related factor 2 pathway by novel natural
products halomadurones A-D and a synthetic analogue.
AB - Two novel chlorinated pyrones, halomadurones A and B, and two novel brominated
analogues, halomadurones C and D, were isolated from a marine Actinomadura sp.
cultivated from the ascidian Ecteinascidia turbinata. Additionally, a non
halogenated analogue, 2-methyl-6-((E)-3-methyl-1,3-hexadiene)-gamma-pyrone, was
synthesized to understand the role of the halogens for activity. Halomadurones C
and D demonstrated potent nuclear factor E2-related factor antioxidant response
element (Nrf2-ARE) activation, which is an important therapeutic approach for
treatment of neurodegenerative diseases.
PMID- 24351908
TI - Polypeptide modulators of TRPV1 produce analgesia without hyperthermia.
AB - Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant
physiological role. The study of novel TRPV1 agonists and antagonists is
essential. Here, we report on the characterization of polypeptide antagonists of
TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of
APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and
single cell Ca2+ imaging. In vivo tests were performed to assess the biological
effects of APHC1 and APHC3 on temperature sensation, inflammation and core body
temperature. In the electrophysiological study, both polypeptides partially
blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid
induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant
antinociceptive and analgesic activity in vivo at reasonable doses (0.01-0.1
mg/kg) and did not cause hyperthermia. Intravenous administration of these
polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced
behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably,
APHC3's ability to inhibit the low pH-induced activation of TRPV1 resulted in a
reduced behavioural response in the acetic acid-induced writhing test, whereas
APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred
to as a new class of TRPV1 modulators that produce a significant analgesic effect
without hyperthermia.
PMID- 24351909
TI - Identification and functional characterization of genes encoding omega-3
polyunsaturated fatty acid biosynthetic activities from unicellular microalgae.
AB - In order to identify novel genes encoding enzymes involved in the biosynthesis of
nutritionally important omega-3 long chain polyunsaturated fatty acids, a
database search was carried out in the genomes of the unicellular
photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom
Fragilariopsis cylindrus. The search led to the identification of two putative
"front-end" desaturases (Delta6 and Delta4) from Ostreococcus RCC809 and one
Delta6-elongase from F. cylindrus. Heterologous expression of putative open
reading frames (ORFs) in yeast revealed that the encoded enzyme activities
efficiently convert their respective substrates: 54.1% conversion of alpha
linolenic acid for Delta6-desaturase, 15.1% conversion of 22:5n-3 for Delta4
desaturase and 38.1% conversion of gamma-linolenic acid for Delta6-elongase. The
Delta6-desaturase from Ostreococcus RCC809 displays a very strong substrate
preference resulting in the predominant synthesis of stearidonic acid
(C18:4Delta6,9,12,15). These data confirm the functional characterization of
omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two
species which have until now not been investigated for such activities. The
identification of these new genes will also serve to expand the repertoire of
activities available for metabolically engineering the omega-3 trait in
heterologous hosts as well as providing better insights into the synthesis of
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae.
PMID- 24351910
TI - Fucoxanthin: a marine carotenoid exerting anti-cancer effects by affecting
multiple mechanisms.
AB - Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti
cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is
well documented. In view of its potent anti-carcinogenic activity, the need to
understand the underlying mechanisms has gained prominence. Towards achieving
this goal, several researchers have carried out studies in various cell lines and
in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and
cancer preventing influence via different molecules and pathways including the
Bcl-2 proteins, MAPK, NFkappaB, Caspases, GADD45, and several other molecules
that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in
addition to decreasing the frequency of occurrence and growth of tumours,
fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this
effect is selective, i.e., fucoxanthin has the capability to target cancer cells
only, leaving normal physiological cells unaffected/less affected. Hence,
fucoxanthin and its metabolites show great promise as chemotherapeutic agents in
cancer.
PMID- 24351911
TI - Bone regeneration of rat tibial defect by zinc-tricalcium phosphate (Zn-TCP)
synthesized from porous Foraminifera carbonate macrospheres.
AB - Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible
and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic
material for bone fracture repair. Zn-TCP samples implanted in a rat tibial
defect model for eight weeks were compared with unfilled defect and beta
tricalcium phosphate showing accelerated bone regeneration compared with the
control groups, with statistically significant bone mineral density and bone
mineral content growth. CT images of the defect showed restoration of cancellous
bone in Zn-TCP and only minimal growth in control group. Histological slices
reveal bone in-growth within the pores and porous chamber of the material
detailing good bone-material integration with the presence of blood vessels.
These results exhibit the future potential of biomimetic Zn-TCP as bone grafts
for bone fracture repair.
PMID- 24351913
TI - Current strategy for successful periradicular surgery.
AB - Periradicular surgery is often used as a last resort to save an endodontically
treated tooth with a persistent periapical lesion. The introduction of surgical
microscopes, ultrasonics, and compatible root-end filling materials has made
periradicular surgery a much more predictable treatment. The advantages of modern
periradicular surgery include easier identification of root apices, smaller
osteotomines, shallower resection angles, and tight sealing within the prepared
root-end cavity. Modern periradicular surgical thus has a much higher success
rate than traditional periradicular surgery.
PMID- 24351912
TI - Synthesis and neuroprotective action of xyloketal derivatives in Parkinson's
disease models.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disease
affecting people over age 55. Oxidative stress actively participates in the
dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural
compounds from marine mangrove fungus strain No. 2508 that have been reported to
protect against neurotoxicity through their antioxidant properties. However,
their protection versus 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity
is only modest, and appropriate structural modifications are necessary to
discover better candidates for treating PD. In this work, we designed and
synthesized 39 novel xyloketal derivatives (1-39) in addition to the previously
reported compound, xyloketal B. The neuroprotective activities of all 40
compounds were evaluated in vivo via respiratory burst assays and longevity
extending assays. During the zebrafish respiratory burst assay, compounds 1, 9,
23, 24, 36 and 39 strongly attenuated reactive oxygen species (ROS) generation at
50 MUM. In the Caenorhabditis elegans longevity-extending assay, compounds 1, 8,
15, 16 and 36 significantly extended the survival rates (p < 0.005 vs. dimethyl
sulfoxide (DMSO)). A total of 15 compounds were tested for the treatment of
Parkinson's disease using the MPP+-induced C. elegans model, and compounds 1 and
8 exhibited the highest activities (p < 0.005 vs. MPP+). In the MPP+-induced
C57BL/6 mouse PD model, 40 mg/kg of 1 and 8 protected against MPP+-induced
dopaminergic neurodegeneration and increased the number of DA neurons from 53%
for the MPP+ group to 78% and 74%, respectively (p < 0.001 vs. MPP+ group). Thus,
these derivatives are novel candidates for the treatment of PD.
PMID- 24351914
TI - Synergistic antibacterial activity of chlorhexidine and hydrogen peroxide against
Enterococcus faecalis.
AB - The aim of the present study was to compare the in vitro antibacterial activity
of common root canal irrigants with a combination technique against intratubular
Enterococcus faecalis. Seventy-five human single-rooted teeth were selected and
their crowns and root-ends were removed to obtain specimens 5 mm in length. The
specimens were contaminated with E. faecalis and divided into five experimental
groups (n = 15). These groups were irrigated with 2% chlorhexidine (CHX), 3%
hydrogen peroxide (H2O2), 5.25% sodium hypochlorite (NaOCl), CHX/H2O2 and sterile
saline (control). Surface and deep dentinal chips were collected for each sample.
After incubation, the numbers of colony-forming units (CFUs) were counted. The
Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis (alpha
= 0.05). In the surface dentin, CHX, NaOCl, and CHX/H2O2 had significantly higher
antibacterial activity than H2O2 (P < 0.05). In the deep dentin, NaOCl and
CHX/H2O2 had significantly higher antibacterial activity than CHX and H2O2 (P <
0.05). CHX/H2O2 had similar antibacterial effectiveness to NaOCl in both surface
and deep dentinal tubules. This combination can be considered a potentially
useful irrigant for root canal treatment.
PMID- 24351915
TI - Genetic variations in MMP9 and MMP13 contribute to tooth agenesis in a Brazilian
population.
AB - We investigated the association between polymorphisms in the MMP2 (rs243865),
MMP9 (rs17576), and MMP13 (rs2252070) genes with tooth agenesis in humans. Two
hundred eighty-five unrelated individuals (202 controls without tooth agenesis
and 83 cases with tooth agenesis) were evaluated in a cross-sectional single
center study. The study participants were recruited through the Pediatric Dental
Clinics of the Federal University of Rio de Janeiro, Brazil. Genotyping of the
selected polymorphisms for MMPs was carried out by real-time PCR using the Taqman
assay method from genomic DNA isolated from buccal epithelial cells of all the
studied individuals. There was no significant association of MMP2 genotype or
allele distribution with tooth agenesis or its absence. For MMP9, a significant
difference in allele frequency was evident between the two groups (P = 0.05).
With regard to the affected side, there was a significant difference between
unilateral tooth agenesis and the control group in the distribution of MMP9 (P =
0.05). Also, there was a significant difference in MMP9 distribution between
tooth agenesis in the maxilla and control individuals (P = 0.03). The genotype
distribution of MMP13 differed significantly between the group with unilateral
tooth agenesis and the controls (P = 0.01). Our findings provide evidence that
MMP9 and MMP13 may be involved in tooth agenesis.
PMID- 24351916
TI - Bacterial analysis of combined periodontal-endodontic lesions by polymerase chain
reaction-denaturing gradient gel electrophoresis.
AB - We used denaturing gradient gel electrophoresis (DGGE) to compare bacterial
profiles in periodontium and root canals of teeth with combined periodontal
endodontic lesions. Samples of dental plaque and necrotic pulp were collected
from thirteen extracted teeth with advanced periodontitis. Genomic DNA was
extracted for polymerase chain reaction (PCR) analysis using universal bacterial
primers. The PCR products were then loaded onto DGGE gels to obtain fractionated
bands. Characteristic DGGE bands were excised and DNA was cloned and sequenced.
The number of bands, which indicates the number of bacterial species, was
compared between dental plaques and necrotic pulp tissues from the same tooth.
Although the difference was statistically significant (P < 0.01), there was no
positive correlation; similarity (Dice coefficient) was 13.1% to 62.5%. Some
bacteria species were present in both the periodontal pockets and root canals of
the same tooth; however, periodontal bacteria did not always invade the root
canals, and some bacteria in root canals were not present in periodontal pockets
of the same tooth. In some teeth, unique bacteria in root canals had not passed
from periodontal pockets. A basic local alignment search tool (BLAST) sequence
search in Genbank indicated that new bacteria species were present in periodontal
pockets and root canals. Their characteristics must thus be further analyzed.
PMID- 24351917
TI - Expression of activation-induced cytidine deaminase in oral epithelial dysplasia
and oral squamous cell carcinoma.
AB - Oral epithelial dysplasia is thought to be a precursor state of carcinogenesis
and may harbor gene alterations. Recently, it was reported that gene editing
enzyme, activation-induced cytidine deaminase (AID), is expressed in precursor
and cancer epithelial cells during carcinogenesis associated with chronic
inflammation/infection and that this enzyme induces mutation of tumor-suppressor
genes. Thus, AID may have a role in carcinogenesis via oral epithelial dysplasia.
In this study, we classified oral mucosal epithelium exhibiting epithelial
dysplasia as squamous intraepithelial neoplasia (SIN) grades 1-3, according to
the 2005 World Health Organization classification, and used immunohistochemical
techniques to examine AID expression in oral mucosal epithelium exhibiting SIN
and oral cancer tissues. AID was observed in prickle cells in oral mucosal
epithelium with epithelial dysplasia and in oral cancer cells. Additionally, to
investigate the mechanism of AID expression and its role in cancer progression,
we incubated the oral cancer cell line HSC-2 with inflammatory cytokines. In the
HSC-2 cell line, AID expression was enhanced by TNF-alpha via NF-kappaB
activation and promoted expression of N-cadherin by regulating Snail expression.
These findings suggest that AID has a role in the development of oral epithelial
dysplasia and promotes progression of oral cancer.
PMID- 24351918
TI - Effect of SI-R20401 to remineralize artificial incipient enamel lesions in
primary teeth.
AB - We evaluated the effectiveness of the experimental surface pre-reacted glass
ionomer coating (SI-R20401) to remineralize artificial enamel lesions in primary
teeth. For each of 12 sound primary molars, five regions were assigned, based on
whether enamel was unground or ground and whether PRG coating was applied. The
teeth were demineralized in 10% EDTA for 7 h and lactic acid solution for 3 days
and immersed in artificial saliva (Group 1), demineralizing medium (Group 2) or
deionized water (Group 3) for 1 month. DIAGNOdent reading, nanoindentation test
and scanning electron microcopy/energy dispersive X-ray analysis were performed.
Data were analyzed using analysis of variance and the Fisher protected least
significance difference test at alpha = 0.05. After immersion, a decrease in
DIAGNOdent value for the demineralized enamel was observed only in the
unground/non-PRG region of Group 1. In the ground/PRG region of Groups 1 and 3,
the hardness and Young's modulus at the enamel surface were significantly higher
than those at subsurface points. For unground enamel, Ca%, P%, and the Ca/P ratio
at the enamel surface of the non-PRG region were significantly lower than those
at subsurface points. In Group 2, scanning electron microcopy showed greater
demineralization at the unground/non-PRG region compared with the unground/PRG
region. Efficacy of SI-R20401 to remineralize the enamel lesions in primary teeth
was partially observed, however, to arrest the lesion could not be demonstrated.
PMID- 24351919
TI - Meteorological influences on the incidence of lichen planus in a north Indian
population.
AB - Lichen planus is a chronic, autoimmune, mucocutaneous disease that shows
differences in clinical presentation at different times of the year. The present
retrospective study was conducted to clarify the meteorological factors that
influence the incidence of lichen planus, as well as the general features and
clinical presentation of this condition during three consecutive years, 2008,
2009, and 2010, in Moradabad district (Western Uttar Pradesh, India). The study
group comprised 1,355 patients extracted from the records of the outpatient
department of Kothiwal Dental College Research Centre and Hospital, who were
clinically diagnosed as having lichen planus during this three-year period. The
highest number of patients (735) were recorded in summer, and the lowest (56) in
winter. Females were affected more often, and psychosocial influences were also
evident. There were significant differences in the incidence of lichen planus in
different seasons, and the summer peak was attributable to the intensity of sun
exposure (actinic lichen planus and summertime lichen planus).
PMID- 24351920
TI - Expression of the IGF-1, IGFBP-3 and IGF-1 receptors in dental pulp stem cells
and impacted third molars.
AB - IGF-1 regulates the metabolism of hard dental tissue through binding to the IGF-1
receptor on target cells. Furthermore, IGF-binding-protein-3 promotes the
accessibility of IGF-1. The aim of this study was to investigate the expression
of IGF-1, IGFBP-3 and IGF-1R in STRO-1-positive dental pulp stem cells (DPSCs)
and fully impacted wisdom teeth in relation to tooth development. Third molars
were surgically removed from 60 patients and classified into two groups: teeth
showing ongoing development (group 1) and teeth that had completed root shaping
(group 2). The transcript and protein levels of IGF-1, IGFBP-3 and IGF-1R were
investigated using RT-PCR and immunohistochemistry. The expression of the same
proteins was also analyzed in DPSCs. The teeth from group 1 showed significantly
stronger expression of IGF-1 and IGF-1R. The major sources of all of the proteins
investigated immunohistochemically in sections of wisdom teeth were odontoblasts,
cementoblasts and cell colonies in the pulpal mesenchyme. These colonies were
identified as stem cells in view of their positivity for STRO-1, and the cells
were subsequently sorted by flow cytometry. These DPSCs demonstrated high levels
of pluripotency markers and IGF-1 and IGF-1R. We conclude that members of the IGF
1 family are involved in the late stage of tooth development and the process of
pulpal differentiation.
PMID- 24351921
TI - Prevalence and risk factors for dental erosion among 11- to 14-year-old school
children in South India.
AB - This cross-sectional survey was conducted to assess the prevalence and severity
of dental erosion and to determine the potential risk factors for dental erosion
among 11- to 14-year-old school children in South India. The total sample size
for the study was 605, of which 303 school children were from private schools and
302 from public schools. A questionnaire was designed to record information about
socio-demographic characteristics, oral hygiene practices, dietary habits and
risk factors for dental erosion. Chi square test, bivariate analysis and Logistic
regression analysis were performed to analyse the data. The children who consumed
lemon several times a day (OR = 13.41, P < 0.001), and those who preferred
carbonated drinks (OR = 2.80, P = 0.007) had a higher tendency to develop dental
erosion. The overall prevalence of dental erosion was found to be low (8.9%).
Erosion was found to be greater in posterior teeth (65.6%) than anterior teeth
(34.4%). Loss of enamel only with loss of surface contour was observed in most
(94.8%) of the cases. The prevalence of dental erosion was found to be low in
school children. Private school children were affected more by dental erosion.
Frequency of lemon consumption and consumption of carbonated drinks were
identified as risk factors.
PMID- 24351922
TI - Linear reciprocal interaction between dental caries and salivary characteristics.
AB - Carious tooth surfaces can alter saliva in various ways. We investigated whether
salivary parameters were affected by elimination of existing active dental caries
in 99 children (age 6-12 years) with more than five carious tooth surfaces.
Unstimulated saliva samples were obtained from each child, and salivary
characteristics were evaluated. One month after caries treatment that eliminated
all existing dental caries, saliva sampling and analysis were repeated. Saliva
viscosity significantly decreased (P = 0.04), while pH and saliva buffering
capacity significantly increased (P < 0.001). There was no significant difference
in unstimulated salivary production at the start of the study and 1 month after
caries elimination (P > 0.05). The relationship between dental caries and
salivary condition is reciprocal. Treatment of existing dental caries can prevent
future caries by improving saliva quality.
PMID- 24351923
TI - Bone regeneration with systemic administration of lactoferrin in non-critical
sized rat calvarial bone defects.
AB - Using in vivo microfocus computed tomography (micro-CT) and tissue sections, we
evaluated bone regeneration in non-critical-sized rat calvarial flat bone defects
during systemic administration of lactoferrin (LF). Ten 11-week-old male Fischer
rats were used. Non-critical-sized calvarial bone defects (diameter, 2.7 mm) were
trephined into the dorsal parietal bone on both sides of the midsagittal suture,
and a collagen sponge soaked in saline was placed on each side. LF was injected
intraperitoneally every day, starting on the day of the operation (day 0; groups:
control, 10 mg/kg LF, 100 mg/kg LF). Micro-CT imaging was performed repeatedly
from 1 to 4 weeks after surgery. The defect sites were then removed, along with
surrounding bone and soft tissues, and stained with hematoxylin and eosin. During
weeks 1-4, micro-CT showed a significant difference in reossification ratio
between the controls and the 100 mg/kg LF group. Histological analysis revealed
that there were more osteoblast-like cells around the bony rim in the 100 mg/kg
group than in the control group. In summary, micro-CT and histological analyses
showed that systemic administration of LF accelerated bone regeneration in non
critical-sized rat calvarial bone defects.
PMID- 24351924
TI - Chewing ability and associated factors in a Sudanese population.
AB - This study aimed to assess self-reported chewing ability among a sample of
Sudanese adults and to identify factors associated with impaired oral function. A
total of 1,888 adults (>=16 years old) attending outpatient clinics in Khartoum
State were included. Subjective chewing ability was assessed by interviewing
participants on chewing complaints and perceived difficulty of chewing 15 common
Sudanese foods. Pearson and multivariate analyses were used to examine
relationships between chewing ability and characteristics obtained from
interviews and clinical examination. Chewing complaints were reported by 33.5% of
subjects; 15.2-33.4% had perceived difficulty of chewing hard foods, whereas only
1.5-6.9% had difficulty eating soft foods. The likelihood of chewing complaints
was higher in people with dry mouth, <20 teeth, tooth decay, poor self-rated oral
health, perceived difficulty of chewing, and higher oral health-related quality
of life (OHRQoL) scores. Individuals with <20 teeth, poor self-rated general
health, and higher OHRQoL scores were all more likely to have perceived
difficulty of chewing certain foods. Impaired chewing ability was rather highly
prevalent among Sudanese adults. Addressing factors such as dry mouth and tooth
loss/decay, which have been identified to be associated with impaired oral
function, might help to decrease the risk of omission of essential foods from the
diet and improve OHRQoL.
PMID- 24351925
TI - Aggressive periodontitis in a young Pakistani female with laryngo-onycho
cutaneous syndrome.
AB - The periodontal status of patients with laryngo-onycho-cutaneous syndrome is
unknown. This study describes a case of severe aggressive periodontitis in a 19
year-old American-Pakistani female with laryngo-onycho-cutaneous syndrome. The
patient showed abundant dental plaque and calculus accumulations, suppuration and
hemorrhage from virtually all gingivae and interdental papillae, and extensive
radiographic alveolar bone loss and vertical mobility of several teeth.
Subgingival plaque samples revealed a variety of major periodontal pathogens. The
patient was scheduled for full-mouth tooth extraction.
PMID- 24351926
TI - The usefulness of an autologous blood clot combined with gelatin for regeneration
of periodontal tissue.
AB - Several growth factors have been used in tissue regeneration therapy. Here we
describe the use of an autologous blood clot combined with gelatin for teeth
affected by severe periodontitis and vertical root fracture treated using three
oral surgical procedures: periodontal flap surgery, intentional tooth
replantation (IR), and tooth autotransplantation. Treatment with a blood clot
improved the condition of the periodontal tissue, including reduction of pocket
depth. Radiographical images demonstrated no evidence of ankylosis, and revealed
the presence of alveolar bone regeneration. Our successful clinical outcome
suggests that use of an autologous blood clot combined with gelatin is clinically
effective for regeneration of lost periodontal tissue.
PMID- 24351927
TI - Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2
and disrupts its interaction with 14-3-3.
AB - Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein implicated in
Parkinson disease (PD); however, the molecular mechanism and mode of action of
this protein remain elusive. cAMP-dependent protein kinase (PKA), along with
other kinases, has been suggested to be an upstream kinase regulating LRRK2
function. Using MS, we detected several sites phosphorylated by PKA, including
phosphorylation sites within the Ras of complex proteins (ROC) GTPase domain as
well as some previously described sites (S910 and S935). We systematically mapped
those sites within LRRK2 and investigated their functional consequences. S1444 in
the ROC domain was confirmed as a target for PKA phosphorylation using ROC single
domain constructs and through site-directed mutagenesis. Phosphorylation at S1444
is strikingly reduced in the major PD-related LRRK2 mutations R1441C/G/H, which
are part of a consensus PKA recognition site ((1441)RASpS(1444)). Furthermore,
our work establishes S1444 as a PKA-regulated 14-3-3 docking site. Experiments of
direct binding to the three 14-3-3 isotypes gamma, theta, and zeta with
phosphopeptides encompassing pS910, pS935, or pS1444 demonstrated the highest
affinities to phospho-S1444. Strikingly, 14-3-3 binding to phospho-S1444
decreased LRRK2 kinase activity in vitro. Moreover, substitution of S1444 by
alanine or by introducing the mutations R1441C/G/H, abrogating PKA
phosphorylation and 14-3-3 binding, resulted in increased LRRK2 kinase activity.
In conclusion, these data clearly demonstrate that LRRK2 kinase activity is
modulated by PKA-mediated binding of 14-3-3 to S1444 and suggest that 14-3-3
interaction with LRRK2 is hampered in R1441C/G/H-mediated PD pathogenesis.
PMID- 24351928
TI - Celastrol increases glucocerebrosidase activity in Gaucher disease by modulating
molecular chaperones.
AB - Gaucher disease is caused by mutations in the glucosidase, beta, acid gene that
encodes glucocerebrosidase (GCase). Glucosidase, beta, acid mutations often cause
protein misfolding and quantitative loss of GCase. In the present study, we found
that celastrol, an herb derivative with known anticancer, anti-inflammatory, and
antioxidant activity, significantly increased the quantity and catalytic activity
of GCase. Celastrol interfered with the establishment of the heat-shock protein
90/Hsp90 cochaperone Cdc37/Hsp90-Hsp70-organizing protein chaperone complex with
mutant GCase and reduced heat-shock protein 90-associated protein degradation. In
addition, celastrol modulated the expression of molecular chaperones. Bcl2
associated athanogene 3 and heat shock 70kDa proteins 1A and 1B were
significantly increased by celastrol. Furthermore, BAG family molecular chaperone
regulator 3 assisted protein folding and maturation of mutant GCase. These
findings provide insight into a therapeutic strategy for Gaucher disease and
other human disorders that are associated with protein misfolding.
PMID- 24351929
TI - Structure of a eukaryotic thiaminase I.
AB - Thiaminases, enzymes that cleave vitamin B1, are sporadically distributed among
prokaryotes and eukaryotes. Thiaminase I enzymes catalyze the elimination of the
thiazole ring moiety from thiamin through substitution of the methylene group
with a nitrogenous base or sulfhydryl compound. In eukaryotic organisms, these
enzymes are reported to have much higher molecular weights than their bacterial
counterparts. A thiaminase I of the single-celled amoeboflagellate Naegleria
gruberi is the only eukaryotic thiaminase I to have been cloned, sequenced, and
expressed. Here, we present the crystal structure of N. gruberi thiaminase I to a
resolution of 2.8 A, solved by isomorphous replacement and pseudo-two-wavelength
multiwavelength anomalous diffraction and refined to an R factor of 0.231 (Rfree,
0.265). This structure was used to solve the structure of the enzyme in complex
with 3-deazathiamin, a noncleavable thiamin analog and enzyme inhibitor (2.7 A;
R, 0.233; Rfree, 0.267). These structures define the mode of thiamin binding to
this class of thiaminases and indicate the involvement of Asp272 as the catalytic
base. This enzyme is able to use thiamin as a substrate and is active with amines
such as aniline and veratrylamine as well as sulfhydryl compounds such as l
cysteine and beta-mercaptoethanol as cosubstrates. Despite significant
differences in polypeptide sequence and length, we have shown that the N. gruberi
thiaminase I is homologous in structure and activity to a previously
characterized bacterial thiaminase I.
PMID- 24351930
TI - Contribution of phenotypic heterogeneity to adaptive antibiotic resistance.
AB - Antibiotic-resistant isolates of Salmonella enterica were selected on plates
containing lethal concentrations of rifampicin, kanamycin, and nalidixic acid.
The stability of the resistance phenotype was scored after nonselective growth.
Rifampicin-resistant (Rif(r)) isolates were stable, suggesting that they had
arisen by mutation. Mutations in the rpoB gene were detected indeed in Rif(r)
mutants. In contrast, a fraction of kanamycin-resistant (Km(r)) and nalidixic
acid-resistant (Nal(r)) isolates showed reduced resistance after nonselective
growth, suggesting that mechanisms other than mutation had contributed to
bacterial survival upon lethal selection. Single-cell analysis revealed
heterogeneity in expression of the porin gene ompC, and subpopulation separation
provided evidence that reduced ompC expression confers adaptive resistance to
kanamycin. In the case of Nal(r) isolates, mutations in the gyrA gene were
present in most nalidixic acid-resistant isolates. However, the efflux pump
inhibitor Phe-Arg-beta-naphtylamide (PAbetaN) reduced the level of resistance in
Nal(r) mutants, indicating that active efflux contributes to the overall level of
nalidixic acid resistance. Heterogeneous efflux pump activity was detected in
single cells and colonies, and a correlation between high efflux and increased
resistance to nalidixic acid was found. These observations suggest that
fluctuations in the expression and the activity of critical functions of the
bacterial cell, alone or combined with mutations, can contribute to adaptive
resistance to antibiotics.
PMID- 24351932
TI - Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal
genetic programs to specify striatonigral cell identity.
AB - Striatal projection neurons comprise two populations of striatonigral and
striatopallidal neurons. These two neuronal populations play distinct roles in
controlling movement-related functions in the basal ganglia circuits. An
important issue is how striatal progenitors are developmentally specified into
these two distinct neuronal populations. In the present study, we characterized
the function of Islet-1 (Isl1), a LIM-homeodomain transcription factor, in
striatal development. Genetic fate mapping showed that Isl1(+) progeny
specifically developed into a subpopulation of striatonigral neurons that
transiently expressed Isl1. In Nestin-Cre;Isl1(f/f) KO mouse brain,
differentiation of striatonigral neurons was defective, as evidenced by decreased
expression of striatonigral-enriched genes, including substance P, prodynorphin,
solute carrier family 35, member D3 (Slc35d3), and PlexinD1. Striatonigral axonal
projections were also impaired, and abnormal apoptosis was observed in Isl1 KO
striatum. It was of particular interest that striatopallidal-enriched genes,
including dopamine D2 receptor (Drd2), proenkephalin, A2A adenosine receptor
(A2aR) and G protein-coupled receptor 6 (Gpr6), were concomitantly up-regulated
in Isl1 mutant striatum, suggesting derepression of striatopallidal genes in
striatonigral neurons in the absence of Isl1. The suppression of striatopallidal
genes by Isl1 was further examined by overexpression of Isl1 in the striatum of
Drd2-EGFP transgenic mice using in utero electroporation. Ectopic Isl1 expression
was sufficient to repress Drd2-EGFP signals in striatopallidal neurons. Taken
together, our study suggests that Isl1 specifies the cell fate of striatonigral
neurons not only by orchestrating survival, differentiation, and axonal
projections of striatonigral neurons but also by suppressing striatopallidal
enriched genes. The dual action of developmental control by Isl1 in promoting
appropriate striatonigral but repressing inappropriate striatopallidal genetic
profiles may ensure sharpening of the striatonigral identity during development.
PMID- 24351933
TI - Fe-vacancy order and superconductivity in tetragonal beta-Fe1-xSe.
AB - Several superconducting transition temperatures in the range of 30-46 K were
reported in the recently discovered intercalated FeSe system (A1-xFe2-ySe2, A =
K, Rb, Cs, Tl). Although the superconducting phases were not yet conclusively
decided, more than one magnetic phase with particular orders of iron vacancy
and/or potassium vacancy were identified, and some were argued to be the parent
phase. Here we show the discovery of the presence and ordering of iron vacancy in
nonintercalated FeSe (PbO-type tetragonal beta-Fe1-xSe). Three types of iron
vacancy order were found through analytical electron microscopy, and one was
identified to be nonsuperconducting and magnetic at low temperature. This
discovery suggests that the rich-phases found in A1-xFe2-ySe2 are not exclusive
in Fe-Se and related superconductors. In addition, the magnetic beta-Fe1-xSe
phases with particular iron-vacancy orders are more likely to be the parent phase
of the FeSe superconducting system instead of the previously assigned beta
Fe1+deltaTe.
PMID- 24351931
TI - Drastic neofunctionalization associated with evolution of the timezyme AANAT 500
Mya.
AB - Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night:
circulating levels at night are markedly higher than day levels. This increase is
driven by precisely regulated increases in acetylation of serotonin in the pineal
gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in
the synthesis of melatonin. This unique essential role of AANAT in vertebrate
timekeeping is recognized by the moniker the timezyme. AANAT is also found in the
retina, where melatonin is thought to play a paracrine role. Here, we focused on
the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and
Chondrichthyes (catshark and elephant shark) were cloned, and it was found that
pineal glands and retinas from these groups express a form of AANAT that is
compositionally, biochemically, and kinetically similar to AANATs found in bony
vertebrates (VT-AANAT). Examination of the available genomes indicates that VT
AANAT is absent from other forms of life, including the Cephalochordate
amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that
VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate
Vertebrate split over one-half billion years ago. The emergence of VT-AANAT
apparently involved a dramatic acceleration of evolution that accompanied
neofunctionalization after a duplication of the nonvertebrate AANAT gene. This
scenario is consistent with the hypotheses that the advent of VT-AANAT
contributed to the evolution of the pineal gland and lateral eyes from a common
ancestral photodetector and that it was not a posthoc recruitment.
PMID- 24351934
TI - Right ventricular stroke volume variation: a tool to assess right ventricular
volume responsiveness.
AB - BACKGROUND: So far, only left ventricular functional preload indices are used as
a routine to assess volume responsiveness. Right ventricular (RV) functional
preload indices have been described, but offer no continuous monitoring. METHODS:
Following ethical approval, a pressure-induced right ventricular failure (RVF)
was induced with continuous infusion of a thromboxane-A2-analogue (U46619) in 15
anesthetized and ventilated pigs. Before and after increasing mean pulmonary
artery pressure (MPAP) by 50%, right ventricular stroke volume variation (RVSVV)
was assessed with an ultrasonic pulmonary artery flow probe. Measurements were
repeated following volume depletion (- 300 mL) and stepwise retransfusion (200 mL
of whole blood and 200 mL of a colloid solution). RESULTS: A significant and
systematic increase in RVSVV during induction of RVF was observed. Volume
depletion led to an increase in RVSVV and re-transfusion led to a decrease in
RVSVV. RVSVV was higher and a significant decrease in RVSVV was present in all
animals experiencing an increase in CO by more than 5% during retransfusion.
CONCLUSION: RVSVV seems to reflect volume requirement of the right ventricle and
it might prove a reliable parameter to assess volume responsiveness in RVF.
PMID- 24351935
TI - Real-time dosimeter employed to evaluate the half-value layer in CT.
AB - Half-value layer (HVL) measurements on commercial whole body computer tomography
(CT) scanners require serial measurements and, in many institutions, the presence
of a service engineer. An assembly of aluminum filters (AAF), designed to be used
in conjunction with a real-time dosimeter, was developed to provide estimates of
the HVL using clinical protocols. Two real-time dose probes, a solid-state and
air ionization chamber, were examined. The AAF consisted of eight rectangular
filters of high-purity aluminum (Type 1100), symmetrically positioned to form a
cylindrical 'cage' around the probe's detective volume. The incident x-ray beam
was attenuated by varying thicknesses of aluminum filters as the gantry completed
a minimum of one rotation. Measurements employing real-time chambers were
conducted both in service mode and with a routine abdomen/pelvis protocol for
several combinations of x-ray tube potentials and bow tie filters. These
measurements were validated against conventional serial HVL measurements. The
average relative difference between the HVL measurements using the two methods
was less than 5% when using a 122 mm diameter AAF; relative differences were
reduced to 1.1% when the diameter was increased to 505 mm, possibly due to
reduced scatter contamination. Use of a real-time dose probe and the AAF allowed
for time-efficient measurements of beam quality on a clinical CT scanner using
clinical protocols.
PMID- 24351936
TI - Endospores of thermophilic bacteria as tracers of microbial dispersal by ocean
currents.
AB - Microbial biogeography is influenced by the combined effects of passive dispersal
and environmental selection, but the contribution of either factor can be
difficult to discern. As thermophilic bacteria cannot grow in the cold seabed,
their inactive spores are not subject to environmental selection. We therefore
conducted a global experimental survey using thermophilic endospores that are
passively deposited by sedimentation to the cold seafloor as tracers to study the
effect of dispersal by ocean currents on the biogeography of marine
microorganisms. Our analysis of 81 different marine sediments from around the
world identified 146 species-level 16S rRNA phylotypes of endospore-forming,
thermophilic Firmicutes. Phylotypes showed various patterns of spatial
distribution in the world oceans and were dispersal-limited to different degrees.
Co-occurrence of several phylotypes in locations separated by great distances
(west of Svalbard, the Baltic Sea and the Gulf of California) demonstrated a
widespread but not ubiquitous distribution. In contrast, Arctic regions with
water masses that are relatively isolated from global ocean circulation (Baffin
Bay and east of Svalbard) were characterized by low phylotype richness and
different compositions of phylotypes. The observed distribution pattern of
thermophilic endospores in marine sediments suggests that the impact of passive
dispersal on marine microbial biogeography is controlled by the connectivity of
local water masses to ocean circulation.
PMID- 24351937
TI - Symbiotic relationships between soil fungi and plants reduce N2O emissions from
soil.
AB - N2O is a potent greenhouse gas involved in the destruction of the protective
ozone layer in the stratosphere and contributing to global warming. The
ecological processes regulating its emissions from soil are still poorly
understood. Here, we show that the presence of arbuscular mycorrhizal fungi
(AMF), a dominant group of soil fungi, which form symbiotic associations with the
majority of land plants and which influence a range of important ecosystem
functions, can induce a reduction in N2O emissions from soil. To test for a
functional relationship between AMF and N2O emissions, we manipulated the
abundance of AMF in two independent greenhouse experiments using two different
approaches (sterilized and re-inoculated soil and non-mycorrhizal tomato mutants)
and two different soils. N2O emissions were increased by 42 and 33% in microcosms
with reduced AMF abundance compared to microcosms with a well-established AMF
community, suggesting that AMF regulate N2O emissions. This could partly be
explained by increased N immobilization into microbial or plant biomass, reduced
concentrations of mineral soil N as a substrate for N2O emission and altered
water relations. Moreover, the abundance of key genes responsible for N2O
production (nirK) was negatively and for N2O consumption (nosZ) positively
correlated to AMF abundance, indicating that the regulation of N2O emissions is
transmitted by AMF-induced changes in the soil microbial community. Our results
suggest that the disruption of the AMF symbiosis through intensification of
agricultural practices may further contribute to increased N2O emissions.
PMID- 24351938
TI - Microbial population and functional dynamics associated with surface potential
and carbon metabolism.
AB - Microbial extracellular electron transfer (EET) to solid surfaces is an important
reaction for metal reduction occurring in various anoxic environments. However,
it is challenging to accurately characterize EET-active microbial communities and
each member's contribution to EET reactions because of changes in composition and
concentrations of electron donors and solid-phase acceptors. Here, we used
bioelectrochemical systems to systematically evaluate the synergistic effects of
carbon source and surface redox potential on EET-active microbial community
development, metabolic networks and overall electron transfer rates. The results
indicate that faster biocatalytic rates were observed under electropositive
electrode surface potential conditions, and under fatty acid-fed conditions.
Temporal 16S rRNA-based microbial community analyses showed that Geobacter
phylotypes were highly diverse and apparently dependent on surface potentials.
The well-known electrogenic microbes affiliated with the Geobacter
metallireducens clade were associated with lower surface potentials and less
current generation, whereas Geobacter subsurface clades 1 and 2 were associated
with higher surface potentials and greater current generation. An association was
also observed between specific fermentative phylotypes and Geobacter phylotypes
at specific surface potentials. When sugars were present, Tolumonas and Aeromonas
phylotypes were preferentially associated with lower surface potentials, whereas
Lactococcus phylotypes were found to be closely associated with Geobacter
subsurface clades 1 and 2 phylotypes under higher surface potential conditions.
Collectively, these results suggest that surface potentials provide a strong
selective pressure, at the species and strain level, for both solid surface
respirators and fermentative microbes throughout the EET-active community
development.
PMID- 24351939
TI - Assessment of heart rate variability in breath holding children by 24 hour Holter
monitoring.
AB - PURPOSE: Previous studies have shown that the underlying pathophysiologic
mechanism in children with breath holding may be generalised autonomic
dysregulation. Thus, we performed cardiac rhythm and heart rate variability
analyses using 24-hour Holter monitoring to evaluate the cardiac effects of
autonomic dysregulation in children with breath-holding spells. METHODS: We
performed cardiac rhythm and heart rate analyses using 24-hour Holter monitors to
evaluate the cardiac effects of autonomic dysregulation in children during a
breath-holding spell. Our study group consisted of 68 children with breath
holding spells - 56 cyanotic type and 12 pallid type - and 39 healthy controls.
RESULTS: Clinical and heart rate variability results were compared between each
spell type - cyanotic or pallid - and the control group; significant differences
(p<0.05) in standard deviation of all NN intervals, mean of the standard
deviations of all NN intervals for all 5-minute segments, percentage of
differences between adjacent RR intervals >50 ms, and square root of the mean of
the sum of squares of the differences between adjacent NN intervals values were
found between the pallid and cyanotic groups. CONCLUSIONS: Holter monitoring for
24 hours and heart rate variability parameters, particularly in children with
pallid spells, are crucial for evaluation of cardiac rhythm changes.
PMID- 24351940
TI - Soluble CD40 ligand release in patients with stable coronary artery disease
during elective stent implantation: effect of drug-eluting stent over bare metal
stent.
AB - OBJECTIVES: We aimed to determine the effect of drug-eluting stent (DES)
implantation on soluble CD40 ligand (sCD40L) levels in patients with stable
coronary artery disease undergoing stent replacement. STUDY DESIGN: Eighty-nine
consecutive patients (33 women, 56 men; mean age 61+/-10 years) with stable
coronary artery disease undergoing stent replacement were recruited. Pre- and
post-procedural blood samples were collected for sCD40L analysis, and differences
in plasma levels were calculated and expressed as delta sCD40L. Total size and
length of implanted stents and pre- and post-dilatation procedures were recorded
for each patient, for possible impact on sCD40L release. Patients were followed
for one year following procedures for possible adverse cardiac events such as
death, myocardial infarction and revascularization. RESULTS: Forty-nine patients
received bare metal stent (BMS) and 40 patients received DES. There were no
differences between BMS- and DES-implanted patients in terms of age, stent size
and length, and delta sCD40L plasma levels. Delta sCD40L was correlated only with
total implanted stent length (r=0.374, p<0.001). Delta sCD40L levels were divided
into quartiles for better determination of the procedural parameters that are
effective on biomarker release. Total stent length (p=0.008), stent size
(p=0.038) and pre-dilatation procedure (p=0.034) were the statistically differing
parameters between delta sCD40L quartiles. Although statistically non
significant, all three adverse events were observed in patients with the highest
quartile (p=0.179). CONCLUSION: Procedural sCD40L release did not differ between
DES- and BMS-implanted stable coronary artery disease patients. Total implanted
stent length, stent size and pre-dilatation procedure were the influential
parameters on procedural sCD40L release.
PMID- 24351941
TI - Endovascular therapy of acute ischemic stroke by interventional cardiologists:
initial national experience.
AB - OBJECTIVES: We report our initial experience with thrombectomy devices in
patients with acute ischemic stroke. STUDY DESIGN: Demographic, clinical, and
angiographic findings of 19 consecutive patients (7 females and 12 males; mean
age 61.4+/-12.5 years) with acute ischemic stroke were evaluated retrospectively.
RESULTS: The mean initial National Institutes of Health Stroke Scale (NIHSS)
score was 19.5+/-5.6. Middle cerebral artery was the occluded artery in all of
the patients (proximal occlusion in 11, distal in 8 and tandem occlusions in 7
patients). Successful revascularization was achieved in 16 patients (84%). The
mean NIHSS score was 8.4+/-8.2 at 24 hours after the procedure, and 60% of
patients showed a modified Rankin scale score of <=2 at 90 days. New occlusion by
migrated emboli was observed in 2 (11%) cases. None of the patients had
experienced post-procedural symptomatic intracerebral hemorrhage; 3 patients died
during the three-month follow-up. In all patients, thrombectomy was performed
with retrievable Solitaire AB stent system. CONCLUSION: This single-center
experience with mechanical thrombectomy devices demonstrated that high success
rates can be achieved by experienced interventional cardiologists in equipped
cath labs throughout the country.
PMID- 24351942
TI - [Evaluation of left ventricular systolic and diastolic functions in patients with
coronary slow flow phenomenon].
AB - OBJECTIVES: In this study, systolic and diastolic function parameters were
measured with conventional and tissue Doppler echocardiography in coronary slow
flow phenomenon (CSFP) patients and compared to those of a control group. STUDY
DESIGN: Sixty patients (49 male; mean age 52.4+/-12.1) in whom CSFP was detected
during coronary angiography study and 30 volunteers with normal coronary arteries
(21 males; mean age 50.2+/-12.1) were included in this study. CSFP was determined
using the TIMI frame count (TFC) method. TIMI frame count was calculated in each
coronary artery using the TFC method. Left ventricular systolic and diastolic
function was assessed by conventional echocardiography and tissue Doppler
imaging. TFC correlation between diastolic function parameters was measured.
RESULTS: Baseline demographic and laboratory results did not differ significantly
between the groups. TIMI frame counts were greater in the CSFP group compared to
controls (p<0.001). Left ventricular ejection fraction (65.93+/-8.06% vs 66.63+/
5.96%), E/A ratio (1.11+/-0.36 vs 1.22+/-0.33), and isovolumetric relaxation time
(IVRT) (85+/-17 cm/s vs 84+/-13 cm/s) measured with conventional echocardiography
showed no significant difference between the two groups. Em (7.0+/-2.1 cm/s vs
7.4+/-1.7 cm/s), Am (7.4+/-2.0 cm/s vs 7.0+/-1.4 cm/s) and E/Em (10+/-3 vs 10+/
1) measured with tissue Doppler echocardiography showed no significant difference
between the two groups. Corrected TIMI frame count for the left descending
coronary artery (cLAD) and mean TFC were not correlated with the E/A ratio,
deceleration time (DT), IVRT, or E/Em ratio. CONCLUSION: Left ventricular
systolic and diastolic functions were preserved in CSFP.
PMID- 24351943
TI - [The coronary slow flow phenomenon: one step forward, two steps back].
PMID- 24351944
TI - [Comparison of controlled pressure belt -allowing mobility to sandbags after
percutaneous coronary intervention: pilot study].
AB - OBJECTIVES: We aimed to investigate the efficacy and safety of a belt mechanism
(anjiobelt), which we developed recently and patented, which allows mobility
after coronary operations and the application of adjustable pressure to the
femoral artery. STUDY DESIGN: Between October 2012 and April 2013, 189
consecutive patients undergoing percutaneous coronary intervention electively or
due to acute coronary syndrome were enrolled. There were 96 patients in the
sandbag group and 93 patients in anjiobelt group. Manual compression was applied
to the femoral artery until reaching primary homeostasis. Then, a 4-5 kilogram
sandbag or anjiobelt was placed. Mobilization was allowed in case of need in the
anjiobelt group. Twenty-four hours after the procedure, superficial bruising in
the femoral region, hematoma, pseudo-aneurysm, and arteriovenous fistula, as
femoral artery complications, were noted using Doppler ultrasound. RESULTS:
Hematoma occurred more frequently in the sandbag group. Hematoma of <1 cm
developed in 52 patients with sandbag and in 25 patients with anjiobelt
(p<0.0001), while hematoma of 1-5 cm developed in 5 patients with sandbag and in
3 patients with anjiobelt (p<0.0001). Femoral artery pseudoaneurysm was seen in 4
patients (2 with anjiobelt, 2 with sandbag; p=0.975). CONCLUSION: Anjiobelt
significantly reduces the incidence of hematoma in comparison to conventional
sandbag in patients undergoing percutaneous coronary intervention. Other
complications of the femoral region in terms of efficiency and safety appear to
be similar to those observed with sandbag. The main problems occurring in these
patients due to absolute immobilization have been eliminated with the anjiobelt.
PMID- 24351945
TI - [Percutaneous closure of secundum atrial septal defects in pediatric and adult
patients: short- and mid-term follow-up results].
AB - OBJECTIVES: We aimed to evaluate the short- and mid-term results of patients with
atrial septal defect (ASD) who were treated with percutaneous closure. STUDY
DESIGN: Seventy-nine patients with secundum ASD (54 female and 25 male; mean age
26.2+/-17.2; range 3 to 71] years) were included in this study. Patients were
evaluated by transthoracic (TTE) and/or transesophageal echocardiography (TEE).
Amplatzer septal occluder (ASO) was used in all patients. In 76 patients, the
procedure was performed under local anesthesia with TTE, while in the other 3
patients, it was performed with general anesthesia with TEE. Patients were
followed up at the 1st, 3rd, 6th and 12th months and annually thereafter. Mean
follow-up time was 13.6+/-6.6 months. RESULTS: Mean diameter of ASDs was 18.2+/
7.5 mm and 20.7+/-8.04 mm during balloon dilatation, and mean diameter of
implanted devices was 22.7+/-8.5 mm. Procedural time was 40.2+/-12.6 minutes and
fluoroscopy time was 10.9+/-4.1 minutes. The procedure was successfully performed
in all patients (100%). One patient with cardiac tamponade died seven days after
cardiac surgery. In two patients, the implanted devices embolized to the
pulmonary circulation. Residual flow was found in three patients immediately
after the procedure, without residual shunts one month after closure. Mild
pericardial effusion in one patient and significant residual shunt due to device
malposition in another were discovered during the follow-up at 1 and 6 months,
respectively, after the procedure. CONCLUSION: Our findings showed that
percutaneous closure of ASDs is successful in most patients with a low
complication rate, and demonstrated that residual shunts do not develop in the
majority of patients in the short- and mid-term.
PMID- 24351946
TI - [Effect of overweight on cardiac function in children].
AB - OBJECTIVES: It is known that obesity is related to heart failure. Asymptomatic
left ventricular diastolic dysfunction (LVDD) is associated with the development
of heart failure. The relationship between subclinical LVDD and overweight in
children is not clear. The purpose of this study was to evaluate the effect of
body mass index (BMI) and waist circumference on left ventricular mass index
(LVMI) and LVDD in overweight children. STUDY DESIGN: A total of 153 children
were enrolled in the study. Of these, 91 were normal weight (age-adjusted BMI: 15
85 percentile), and 62 were overweight (age-adjusted BMI: 85-95 percentile).
After measuring two-dimensional and M-mode echocardiographic variables, left and
right ventricle diastolic functions were assessed by conventional and tissue
Doppler imaging. RESULTS: Compared to controls, overweight children had increased
left atrium, aortic and left ventricular diameters, left ventricular wall
thickness, LVM and LVMI, and septal mitral annulus e', septal e'/a', lateral e',
lateral e'/a', lateral tricuspid annulus e', and e'/a' values. There were
negative correlations between tissue Doppler diastolic parameters (septal mitral
annulus e', lateral mitral annulus e', lateral tricuspid annulus e', septal
mitral annulus e'/a', lateral mitral annulus e'/a', and lateral tricuspid annulus
e'/a') and BMI, waist circumference, insulin, HOMA index, as well as systolic and
diastolic blood pressure. Positive correlations were found between LVMI and BMI
and between LVMI and waist circumference. BMI was found to be the predictor of
decreased mitral anulus septal e', septal e'/a', lateral e', lateral e'/a'.
CONCLUSION: Compared with normal-weight children, overweight children have
decreased LV diastolic function. BMI is associated with a reduction in LV
diastolic function in overweight children.
PMID- 24351947
TI - A case report of superior vena cava obstruction.
AB - We report herein an 83-year-old gentleman with lung cancer who presented with
nausea, complete atrioventricular (AV) block and presyncope. Despite a present
temporary pacemaker, which had been inserted through the femoral vein 5 days
previously, the patient had asystole attacks that resolved with atropine
administration. Coronary angiography demonstrated no critical stenosis. Sick
sinus syndrome was diagnosed, and permanent pacemaker implantation was decided.
However, the guidewire could not be advanced into the superior vena cava (SVC).
Right jugular venogram showed complete obstruction of the SVC. Subsequent
computerized tomography also revealed its obstruction by a large lung tumor.
Special attention should be given to patients with benign or malignant SVC
syndrome before permanent pacemaker implantation.
PMID- 24351948
TI - Cryoballoon pulmonary vein isolation prior to percutaneous atrial septal defect
closure: a case report.
AB - We report the case of a 61-year-old female who was admitted to our department
with progressive dyspnea and palpitation. Transthoracic echocardiography and
transesophageal echocardiography showed a small atrial septal defect (ASD, 8x7
mm). Paroxysmal atrial fibrillation (AF) was detected in Holter monitoring. As
repair of ASD does not significantly reduce the risk of arrhythmias, cryoablation
of AF was performed prior to ASD closure. On cardiac examination at one year,
this combined intervention improved right ventricular function and prevented AF
episodes.
PMID- 24351949
TI - A rare case of quadruple valve infective endocarditis of normal native valves -
the advantage of TEE.
AB - Quadruple valve infective endocarditis of apparently normal native valves is a
relatively uncommon condition, reported particularly in the setting of
intravenous drug use, structural heart disease and immunocompromised state, but
its occurrence outside these settings is rare. Multiple valve endocarditis is
caused by Staphylococcus aureus in the majority of cases. Although Enterococcus
faecalis is a common cause of bacterial infective endocarditis overall, it is
rarely reported to cause multiple valve involvement. The present case is one such
rare report of a patient who had quadruple valve endocarditis of normal native
valves, caused by E. faecalis. Compared to single valve endocarditis, multiple
valve disease is associated more frequently with heart failure, perivalvular
complications and need for heart surgery; hence, early recognition of the extent
of disease and number of valves involved is crucial, as this in turn influences
the management, risk of complications and outcomes. Transthoracic
echocardiography is a widely used first-line tool in the imaging of infective
endocarditis, but transesophageal echocardiography, which is more sensitive,
should be used more frequently to assess the extent of involvement. Extensive
valvular involvement alone does not preclude medical management, and surgical
management should be considered only in those who do not respond to
antimicrobials or in the case of hemodynamic compromise or mechanical
complications.
PMID- 24351950
TI - An impressive image of woven right coronary artery.
AB - Woven coronary artery is a rare congenital anomaly with an unknown etiology. A 53
year-old male presented with exertional chest pain and dyspnea for six months.
Electrocardiogram and transthoracic echocardiography were in normal range.
Dobutamine stress echocardiography revealed reversible ischemia in the inferior
wall. Right coronary angiography showed an 80% stenosis before the sinoatrial
branch and a twisting course of the right coronary artery lumen after it divided
into multiple thin channels. Left coronary angiogram revealed noncritical
lesions. A diagnosis of woven right coronary artery was considered, and he was
discharged with medical therapy.
PMID- 24351951
TI - Spontaneous coronary artery dissection in a healthy adolescent following
consumption of caffeinated "energy drinks".
AB - Spontaneous coronary artery dissection (SCAD) is a rare and uncommon case of
sudden cardiac death and acute coronary syndrome. Herein, we present a 13-year
old boy with chest pain who was diagnosed with acute ST-segment elevation
myocardial infarction associated with SCAD, possibly caused by the consumption of
an energy drink, which has not been reported previously in the pediatric age
group. On coronary angiography, the left anterior descending artery showed
extensive dissection from the distal part of the vessel. Based on the morphology
of the vessel with a dissection and TIMI flow grade III, it was decided to manage
this patient conservatively with close follow-up. The aim of this report is to
highlight the risks associated with the consumption of caffeinated energy drinks
in children.
PMID- 24351952
TI - [Delayed cardiac asystole after percutaneous mitral balloon valvuloplasty].
AB - Percutaneous mitral balloon valvuloplasty (PMBV) is the preferred treatment in
mitral stenosis patients with appropriate valve anatomy, but it may cause
arrhythmic complications rarely. In the literature, the mortality rate associated
with PMBV has been reported as 1%, and a small number of patients developed
atrioventricular block during the process. In this report, we describe a 53-year
old female patient with severe rheumatic mitral stenosis who developed Mobitz
type 2 atrioventricular block and asystole after a successful PMBV operation.
Sinus rhythm was achieved with atropine in this patient. It was thought that the
arrhythmia resulted from calcified plaques on the mitral valve or from conduction
system damage due to high balloon pressure during the process. For the
recognition and treatment of possible arrhythmic complications, it is important
to monitor patients in the intensive care unit for at least 24 hours after PMBV.
PMID- 24351953
TI - Epicardial ventricular tachycardia.
AB - In ventricular tachycardia (VT) arising in the myocardial tissue, the site of
origin may be the endocardium, mid-myocardium or epicardium. The incidence of
epicardial origin varies with the underlying heart disease, and is probably not
more than 20% in ischemic heart disease and higher in non-ischemic
cardiomyopathies. Percutaneous subxiphoid access to the pericardial space has
enabled a non-surgical approach to catheter mapping and ablation of epicardial
VT. Several algorithms are available for electrocardiographic recognition of
epicardial origin. Idiopathic epicardial VTs are rare but may be curable by
catheter ablation. The electrophysiologic principles guiding the mapping and
ablation of epicardial VTs are similar to those used for endocardial VTs, but the
biophysics of energy delivery may be different. Complications of the epicardial
approach are also different from those of endocardial ablation, and specific
precautions have to be taken to protect the coronary arteries and phrenic nerves
and to avoid pericardial tamponade.
PMID- 24351954
TI - Almanac 2013: acute coronary syndromes.
AB - Unstable coronary artery plaque is the most common underlying cause of acute
coronary syndromes(ACS) and can manifest as unstable angina, non-ST segment
elevation infarction (NSTE-ACS), and ST elevation myocardial infarction (STEMI),
but can also manifest as sudden cardiac arrest due to ischaemia induced
tachyarrhythmias. ACS mortality has decreased significantly over the last few
years,especially from the more extreme manifestations of ACS, STEMI, and cardiac
arrest. This trend is likely to continue based on recent therapeutic progress
which includes novel antiplatelet agents such as prasugrel, ticagrelor, and
cangrelor.
PMID- 24351955
TI - Almanac 2013: cardiac arrhythmias and pacing-an editorial overview of selected
research that has driven recent advances in clinical cardiology.
AB - Important advances have been made in the past few years in the fields of clinical
cardiac electrophysiology and pacing. Researchers and clinicians have a greater
understanding of the pathophysiological mechanisms underlying atrial fibrillation
(AF), which has transpired into improved methods of detection,risk
stratification, and treatments. The introduction of novel oral anticoagulants has
provided clinicians with alternative options in managing patients with AF at
moderate to high thromboembolic risk and further data has been emerging on the
use of catheter ablation for the treatment of symptomatic AF.Another area of
intense research in the field of cardiac arrhythmias and pacing is in the use of
cardiac resynchronisation therapy (CRT) for the treatment of patients with heart
failure. Following the publication of major landmark randomised controlled trials
reporting that CRT confers a survival advantage in patients with severe heart
failure and improves symptoms,many subsequent studies have been performed to
further refine the selection of patients for CRT and determine the clinical
characteristics associated with a favourable response. The field of sudden
cardiac death and implantable cardioverter defibrillators also continues to be
actively researched, with important new epidemiological and clinical data
emerging on improved methods for patient selection, risk stratification, and
management. This review covers the major recent advances in these areas related
to cardiac arrhythmias and pacing.
PMID- 24351956
TI - Massive aortic regurgitation in the background of a quadricuspid aortic valve.
PMID- 24351957
TI - Giant thrombosed saccular aneurysm of the ascending aorta.
PMID- 24351958
TI - An unusual co-anomaly: multiple coronary-cameral fistulas and left main coronary
artery arising from the right sinus of Valsalva.
PMID- 24351959
TI - Angiographic sheath fracture and its embolization to the right atrium during
coronary angiography and its successful percutaneous retrieval - an unusual
complication.
PMID- 24351960
TI - Coronary embolism in a patient with massive left atrial thrombus and mechanical
valve thrombus: hybrid treatment with surgery and percutaneous intervention.
PMID- 24351962
TI - Neuropsychological abnormalities in children with the Panayiotopoulos syndrome
point to parietal lobe dysfunction.
AB - Panayiotopoulos syndrome (PS) is a common epilepsy syndrome associated with rare
clinical seizures and unknown localization of the epileptogenic area. Despite
findings of normal development in patients with PS, recent neuropsychological
studies point to subtle and diverse cognitive impairments. No well-outlined
hypothesis about the localization of the brain dysfunction responsible for these
impairments has been proposed. We further explored the cognitive dysfunctions in
PS and made inferences on the most likely anatomical localization of brain
impairment. A group of 19 patients (aged 6-12) with PS was rated according to
spike activity and lateralization. The patients were submitted to a
neuropsychological evaluation to assess general intelligence, memory, language,
visual-perceptual abilities, attention, and executive functions. Using 35-channel
scalp EEG recordings, the N170 face-evoked event-related potential (ERP) was
obtained to assess the functional integrity of the ventral pathway. All patients
with PS showed normal IQ but subtle and consistent neurocognitive impairments.
Namely, we found abnormalities in the copy task of the Rey-Osterrieth Complex
Figure and in the Narrative Memory Test. There was no correlation between
neuropsychological impairments with spike activity and hemispheric spike
lateralization. The N170 ERP was normal in all patients except for one. Our
neuropsychological findings demonstrate impairments in visual-perceptual
abilities and in semantic processing. These findings, paired with the absence of
occipital lobe dysfunction in all neuropsychological studies of PS performed to
this date, support the existence of parietal lobe dysfunction.
PMID- 24351961
TI - Phase change events of volatile liquid perfluorocarbon contrast agents produce
unique acoustic signatures.
AB - Phase-change contrast agents (PCCAs) provide a dynamic platform to approach
problems in medical ultrasound (US). Upon US-mediated activation, the liquid core
vaporizes and expands to produce a gas bubble ideal for US imaging and therapy.
In this study, we demonstrate through high-speed video microscopy and US
interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs)
exhibit unique acoustic behavior that can be detected and differentiated from
standard microbubble contrast agents. Experimental results show that when
activated with short pulses PCCAs will over-expand and undergo unforced radial
oscillation while settling to a final bubble diameter. The size-dependent
oscillation phenomenon generates a unique acoustic signal that can be passively
detected in both time and frequency domain using confocal piston transducers with
an 'activate high' (8 MHz, 2 cycles), 'listen low' (1 MHz) scheme. Results show
that the magnitude of the acoustic 'signature' increases as PFC boiling point
decreases. By using a band-limited spectral processing technique, the droplet
signals can be isolated from controls and used to build experimental
relationships between concentration and vaporization pressure. The techniques
shown here may be useful for physical studies as well as development of droplet
specific imaging techniques.
PMID- 24351963
TI - Involuntary outpatient treatment for mental health problems in Switzerland: a
literature review.
AB - BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each
Swiss canton may propose specific provisions for involuntary outpatient treatment
(community treatment orders (CTOs)) for individuals with mental disorders. AIM:
This review catalogues the legal provisions of the various Swiss cantons for CTOs
and outlines the differences between them. It sets this in the context of
variations in clinical provisions between the cantons. METHODS: Databases were
searched to obtain relevant publications about CTOs in Switzerland. The Swiss
Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory
and all the 26 Cantonal medical officers were contacted to complete the
information. Conference des cantons en matiere de protection des mineurs et des
adultes (COPMA), the authority which monitors guardianship legislation, and Pro
Mente Sana, a patients' right association, were also approached. RESULTS: Three
articles about CTOs in Switzerland were identified. Psychiatric provisions vary
considerably between cantons and only a few could provide complete or even
partial figures for rates of compulsion in previous years. Prior to 2013, only 6
of the 20 cantons, for which information was returned, had any provision for
CTOs. Now, every canton has some form of legal basis but the level of detail is
often limited. In eight cantons, the powers of the measure are not specified (for
example, use of medication). In 12 cantons, the maximum duration of the CTO is
not specified. German speaking cantons and rural cantons are more likely to
specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs
is being introduced despite the absence of convincing international evidence for
their effectiveness or good quality data on current coercive practice. Careful
monitoring and assessment of these new cantonal provisions are essential.
PMID- 24351964
TI - 'Difficulties come to humans and not trees and they need to be faced': a study on
resilience among Indian women experiencing intimate partner violence.
AB - BACKGROUND: Not much is known about factors that contribute to resilience among
women facing intimate partner violence (IPV), particularly from countries where
patriarchy predominates. This qualitative study aimed to gather the perspectives
of Indian women self-identified as resilient in the face of IPV and tried to
understand the strategies and resources that helped them to maintain or regain
resilience. MATERIALS: Data were collected from 16 consenting women who reported
IPV and whose husbands were being treated for alcohol problems at a psychiatric
centre in Bangalore, India. A semi-structured guided interview format that aimed
at understanding factors that enabled them to feel resilient despite IPV in their
challenging circumstances was used to gather narratives from the participants.
DISCUSSION: Six themes were identified using QSR NVivo software. They were as
follows: the support of women, men and family; personal attributes; dignity and
work; being strong for the children; and faith in God. Among these women,
supportive social networks, personal attributes and aspirations were major
clusters contributing to resilience. CONCLUSION: Attention to these factors may
provide an important, strengths-based perspective for interventions to enhance
women's resilience when facing IPV.
PMID- 24351965
TI - Do newspaper reports of suicides comply with standard suicide reporting
guidelines? A study from Bangalore, India.
AB - BACKGROUND: Several countries have prescribed standard guidelines for media
professionals on suicide reporting. However, the implementation of these
guidelines has been varied. Suicide rates in South Asia are one of the highest in
the world, and it is known that media guidelines for suicide reporting are not
followed adequately. However, there are no published reports available from this
region. AIM: This study aimed at assessing newspaper reports of suicide for
quality of reporting based on standard reporting guidelines and to study
differences between English and vernacular (Kannada) newspapers in Bangalore,
South India. METHODS: A total of 341 newspaper reports of suicide from 550
newspapers (3 English and 3 Kannada) over 3 months were systematically assessed
for compliance with reporting guidelines. Each report was evaluated on 2 domains
and 36 parameters. Data were analyzed for frequency of inappropriate reporting
and patterns compared between vernacular and English newspapers. RESULTS: In all,
87% of the reports were those of completed suicide. Non-compliant reporting -
method of suicide was reported in 89% and 32% of reports were in prominent pages
of the newspaper, 95% mentioned gender, 90% reported the name, 80% reported age
and suicide location, 75% reported life events related to suicide, 70% reported
occupation, 69% had headline explicity on suicide and 61% reported monocausality.
Only 16% reported mental disorder related to suicide, and less than 3% included
information on suicide prevention and helplines. Vernacular papers showed
significantly better compliance in 16 of the 20 areas. However, protective
characteristics were better reported in English newspapers. CONCLUSION: Majority
of reports on suicides in newspapers from Bangalore did not comply with standard
guidelines of reporting. There is a strong need to evolve local guidelines and
mechanisms for ensuring responsible reporting which have important implications
in prevention of suicide.
PMID- 24351966
TI - General health workers' description of mental health problems and treatment
approaches used in Papua New Guinea.
AB - BACKGROUND: Papua New Guinea is a developing country with limited resources for
specialist mental health services. Little is known about the mental health and
treatment services of Papua New Guinea. AIM: The aim of this study was to clarify
the presenting mental health problems encountered by Papua New Guinean health
workers and the common treatment approaches used. METHODS: A total of 203 Papua
New Guinean health workers completed a retrospective quantitative survey about
their three most recent mental health patients. The survey asked about presenting
symptomatology, diagnoses (including culture-bound diagnoses) and treatment
approaches. RESULTS: The major presenting mental health problems for males
included schizophrenia, substance use disorder, sorcery and spirit possession.
Depression was the most common diagnoses for women, followed by sorcery and
somatisation. Over 65% of patients were prescribed psychotropic medication, over
50% received some form of psychological intervention and 28% were receiving
traditional treatments. CONCLUSIONS: Somatic symptoms are common among both male
and female Papua New Guineans; however, males may be more likely to present with
psychotic symptoms and females with mood-related problems. Schizophrenia and
depression are commonly identified with substance use disorder more problematic
among males. Culture-specific explanations and treatment are commonly used.
PMID- 24351968
TI - Recurrent spontaneous splenic rupture in a patient with congenital factor XIII
deficiency.
AB - We describe an unusual presentation of factor XIII (FXIII) deficiency in a 17
year-old boy who was diagnosed with this congenital deficiency at the age of 18
months. He had a history of spontaneous splenic rupture 8 years ago, which was
managed conservatively. He now presented with sudden severe abdominal and left
shoulder pain for 1 day, with no history of antecedent trauma. He was in shock,
and examination revealed diffuse peritonitis. A computed tomography scan showed a
grade IV splenic laceration. He was taken as an emergency to the operating room
where he was found to have a shattered spleen, and a splenectomy was performed.
He received cryoprecipitate transfusions perioperatively. After an uneventful
recovery, the patient was discharged. To the best of our knowledge, this is the
first described case of a recurrent splenic rupture in a patient with FXIII
deficiency.
PMID- 24351967
TI - Reducing stigma toward people with bipolar disorder: impact of a filmed
theatrical intervention based on a personal narrative.
AB - BACKGROUND: Stigma toward people with bipolar disorder (BD) is pervasive and can
have many negative repercussions. Common approaches to stigma reduction include
education and intergroup contact. From this perspective, the Collaborative
RESearch Team to study psychosocial issues in Bipolar Disorder (CREST.BD) and
Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to develop an
intervention to combat stigma. The result is a personal narrative intervention
that combines contact, education and drama to educate audiences and dispel the
myths that drive stigma. AIM: This study reports on the impact of the CREST.BD
CANMAT stigma-reduction intervention in filmed format. METHODS: A sample of 137
participants was recruited to view the film, including health-care service
providers, university students in a health-care-related course, people with BD
and their friends and family members and the general public. Participants were
evaluated for stigmatizing attitudes and the desire for social distance before
and after the intervention and 1 month later. RESULTS: For health-care service
providers, the intervention was associated with statistically significant
improvements in several categories of stigmatizing attitudes, with maintenance 1
month later. The impact was more modest for the other subsamples. Students
demonstrated progressive, significant improvements in the desire for (less)
social distance. Some improvements were observed among members of the BD
community and the general public, but these were limited and eroded over time.
CONCLUSION: This study demonstrated that a filmed dramatic intervention based on
the lived experience of BD has statistically significant, sustainable stigma
reduction impacts for health-care service providers and more limited impacts for
other target groups. This intervention can be considered an effective tool for
use in stigma-reduction campaigns specifically targeting members of the health
care sector. Results are discussed in the context of multi-component stigma
reduction campaigns and the potential needs of target groups.
PMID- 24351969
TI - Recurrent ascites in a patient with low-grade astrocytoma and ventriculo
peritoneal shunt treated with the multikinase inhibitor sorafenib.
AB - This report describes a 6-year-old boy with disseminated low-grade astrocytoma
and ventriculo-peritoneal shunt, who developed recurrent ascites while receiving
sorafenib on a clinical trial. Laboratory analysis of the peritoneal fluid showed
no elevation of protein content and no evidence of underlying infection or tumor
dissemination. This report highlights ascites as a previously unrecognized
adverse reaction to sorafenib in a patient with a ventriculo-peritoneal shunt. We
conclude that such patients should be closely monitored for this complication
when treated with sorafenib.
PMID- 24351970
TI - Germ cell tumors in atypical locations: experience of the TGM 95 SFCE trial.
AB - The yolk sac tumor is one of the most common malignant germ cell tumors in young
children and typically occurs in the gonads. We report 6 cases of children less
than 30 months old with extragonadal atypical locations of yolk sac tumor. These
rare diagnoses were established by raised serum alpha-fetoprotein levels and
biopsies. These patients were treated according to the French TGM 95 trial. All
the patients are alive disease-free after >=2.5 years of follow-up. We want to
highlight the importance of measuring the alpha-fetoprotein levels in very young
children presenting with any midline tumor, even if the tumor is not located in
the typical extragonadal sites such as the sacrococcyx, mediastinum,
retroperitoneum, or vagina.
PMID- 24351971
TI - Patient safety culture in China: a case study in an outpatient setting in
Beijing.
AB - OBJECTIVES: To investigate the patient safety culture in an outpatient setting in
Beijing and explore the meaning and implications of the safety culture from the
perspective of health workers and patients. METHODS: A mixed methods approach
involving a questionnaire survey and in-depth interviews was adopted. Among the
410 invited staff members, 318 completed the Hospital Survey of Patient Safety
Culture (HSOPC). Patient safety culture was described using 12 subscale scores.
Inter-subscale correlation analysis, ANOVA and stepwise multivariate regression
analyses were performed to identify the determinants of the patient safety
culture scores. Interviewees included 22 patients selected through opportunity
sampling and 27 staff members selected through purposive sampling. The interview
data were analysed thematically. RESULTS: The survey respondents perceived high
levels of unsafe care but had personally reported few events. Lack of
'communication openness' was identified as a major safety culture problem, and a
perception of 'penalty' was the greatest barrier to the encouragement of error
reporting. Cohesive 'teamwork within units', while found to be an area of
strength, conversely served as a protective and defensive mechanism for medical
practice. Low levels of trust between providers and consumers and lack of
management support constituted an obstacle to building a positive patient safety
culture. CONCLUSIONS: This study in China demonstrates that a punitive approach
to error is still widespread despite increasing awareness of unsafe care, and
managers have been slow in acknowledging the importance of building a positive
patient safety culture. Strong 'teamwork within units', a common area of
strength, could fuel the concealment of errors.
PMID- 24351972
TI - STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium
entry.
AB - Orai1 calcium channels in the plasma membrane are activated by stromal
interaction molecule-1 (STIM1), an endoplasmic reticulum calcium sensor, to
mediate store-operated calcium entry (SOCE). The cytosolic region of STIM1
contains a long putative coiled-coil (CC)1 segment and shorter CC2 and CC3
domains. Here we present solution nuclear magnetic resonance structures of a
trypsin-resistant CC1-CC2 fragment in the apo and Orai1-bound states. Each CC1
CC2 subunit forms a U-shaped structure that homodimerizes through antiparallel
interactions between equivalent alpha-helices. The CC2:CC2' helix pair clamps two
identical acidic Orai1 C-terminal helices at opposite ends of a hydrophobic/basic
STIM-Orai association pocket. STIM1 mutants disrupting CC1:CC1' interactions
attenuate, while variants promoting CC1 stability spontaneously activate Orai1
currents. CC2 mutations cause remarkable variability in Orai1 activation because
of a dual function in binding Orai1 and autoinhibiting STIM1 oligomerization via
interactions with CC3. We conclude that SOCE is activated through dynamic
interplay between STIM1 and Orai1 helices.
PMID- 24351973
TI - N-terminal protease gene phylogeny reveals the potential for novel cyanobactin
diversity in cyanobacteria.
AB - Cyanobactins are a recently recognized group of ribosomal cyclic peptides
produced by cyanobacteria, which have been studied because of their interesting
biological activities. Here, we have used a PCR-based approach to detect the N
terminal protease (A) gene from cyanobactin synthetase gene clusters, in a set of
diverse cyanobacteria from our culture collection (Laboratory of Ecotoxicology,
Genomics and Evolution (LEGE) CC). Homologues of this gene were found in
Microcystis and Rivularia strains, and for the first time in Cuspidothrix,
Phormidium and Sphaerospermopsis strains. Phylogenetic relationships inferred
from available A-gene sequences, including those obtained in this work, revealed
two new groups of phylotypes, harboring Phormidium, Sphaerospermopsis and
Rivularia LEGE isolates. Thus, this study shows that, using underexplored
cyanobacterial strains, it is still possible to expand the known genetic
diversity of genes involved in cyanobactin biosynthesis.
PMID- 24351975
TI - In memory of Michael D. Lebowitz, Ph.D.
PMID- 24351974
TI - Pre-erythrocytic antibody profiles induced by controlled human malaria infections
in healthy volunteers under chloroquine prophylaxis.
AB - Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by
pre-erythrocytic immunity can be experimentally induced under chloroquine
prophylaxis, through immunization with sporozoites from infected mosquitoes'
bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab)
responses, we developed a proteome microarray containing 809 Pf antigens showing
a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic
life-cycle stages. In contrast, plasma from naturally exposed semi-immune
individuals from Kenya was skewed toward antibody reactivity against asexual
blood stage antigens. CPS-immunized and semi-immune individuals generated
antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens
overlapped between the two groups. Although the number of reactive antigens
varied between the CPS-immunized individuals, all volunteers reacted strongly
against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver
stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were
strongly reactive in semi-immune individuals but lacking in the CPS immunized
group. These data show that the antibody profile of CPS-immunized and semi-immune
groups have quite distinct profiles reflecting their protective immunity;
antibodies from CPS immunized individuals react strongly against pre-erythrocytic
while semi-immune individuals mainly react against erythrocytic antigens.
PMID- 24351976
TI - Orthographic dependency in the neural correlates of reading: evidence from
audiovisual integration in English readers.
AB - Reading skills are indispensible in modern technological societies. In
transparent alphabetic orthographies, such as Dutch, reading skills build on
associations between letters and speech sounds (LS pairs). Previously, we showed
that the superior temporal cortex (STC) of Dutch readers is sensitive to the
congruency of LS pairs. Here, we used functional magnetic resonance imaging to
investigate whether a similar congruency sensitivity exists in STC of readers of
the more opaque English orthography, where the relation among LS pairs is less
reliable. Eighteen subjects passively perceived congruent and incongruent
audiovisual pairs of different levels of transparency in English: letters and
speech sounds (LS; irregular), letters and letter names (LN; fairly transparent),
and numerals and number names (NN; transparent). In STC, we found congruency
effects for NN and LN, but no effects in the predicted direction (congruent >
incongruent) for LS pairs. These findings contrast with previous results obtained
from Dutch readers. These data indicate that, through education, the STC becomes
tuned to the congruency of transparent audiovisual pairs, but suggests a
different neural processing of irregular mappings. The orthographic dependency of
LS integration underscores cross-linguistic differences in the neural basis of
reading and potentially has important implications for dyslexia interventions
across languages.
PMID- 24351978
TI - Clinical and experimental observations of peripheral blood leukocytes and
nucleated bone marrow cells after local irradiation.
AB - AIM: Aim of the study was to observe the impact of bone marrow damage induced by
local irradiation on leukopenia. METHODS: For the human study, five cancer
patients received local radiation therapy. Bone marrow aspiration was conducted
to measure nucleated cell count and 99mTc-Sc sulfur colloid ECT imaging was
carried out to examine bone marrow function. For the animal study, fifty New
Zealand white rabbits were divided into 3 groups: non-irradiated control group
(N.=10), abdomen irradiation group (irradiation area did not cover bone marrow)
(N.=20), chest irradiation group (irradiation area covered bone marrow) (N.=20).
Nucleated cell counts were taken after confirming onset of leukopenia. RESULTS:
Bone marrow of five patients proliferated normally. ECT imaging showed no
abnormality in the pattern of red bone marrow distribution. Hematopoietic
function was mildly active. CONCLUSION: Suppressed myeloproliferative function
does not fully account for irradiation-induced leukopenia.
PMID- 24351977
TI - Gaze-dependent topography in human posterior parietal cortex.
AB - The brain must convert retinal coordinates into those required for directing an
effector. One prominent theory holds that, through a combination of visual and
motor/proprioceptive information, head-/body-centered representations are
computed within the posterior parietal cortex (PPC). An alternative theory,
supported by recent visual and saccade functional magnetic resonance imaging
(fMRI) topographic mapping studies, suggests that PPC neurons provide a
retinal/eye-centered coordinate system, in which the coding of a visual stimulus
location and/or intended saccade endpoints should remain unaffected by changes in
gaze position. To distinguish between a retinal/eye-centered and a head-/body
centered coordinate system, we measured how gaze direction affected the
representation of visual space in the parietal cortex using fMRI. Subjects
performed memory-guided saccades from a central starting point to locations
"around the clock." Starting points varied between left, central, and right gaze
relative to the head-/body midline. We found that memory-guided saccadotopic maps
throughout the PPC showed spatial reorganization with very subtle changes in
starting gaze position, despite constant retinal input and eye movement metrics.
Such a systematic shift is inconsistent with models arguing for a retinal/eye
centered coordinate system in the PPC, but it is consistent with head-/body
centered coordinate representations.
PMID- 24351979
TI - Evaluation of innate immune responses in bovine forestomachs.
AB - Previous studies had indicated an active role of bovine forestomachs in the
response to alimentary disorders as well as to inflammatory and infectious
processes in both the gastro-intestinal (GI) tract and elsewhere. We investigated
the potential of bovine forestomachs to receive, elaborate and produce signals
and mediators of the innate immune response. Indeed, we detected the expression
of Toll IL-1R8/single Ig IL-1-related receptor (TIR8/SIGIRR) and other receptors
and cytokines, such as Toll-like receptor (TLR)4, interleukin (IL)-1beta, IL-10
and Caspase-1 in the forestomach walls of healthy cows. Their presence suggests
an active role of forestomachs in inflammatory disorders of the GI tract and
other body compartments. Moreover, interferon (IFN)-gamma was revealed in ruminal
content. We confirmed and further characterized the presence of leukocytes in the
rumen fluids. In particular, T-, B-lymphocytes and myeloid lineage cells were
detected in the ruminal content of both rumen-fistulated heifers and diseased
cows. An acidogenic diet based on daily supplements of maize was shown to inhibit
leukocyte accumulation, as opposed to a control, hay-based diet, with or without
a soy flour (protein) supplement. On the whole, results indicate that bovine
forestomachs can receive and elaborate signals for the immune cells infiltrating
the rumen content or other organs. Forestomachs can thus participate in a cross
talk with the lymphoid tissues in the oral cavity and promote regulatory actions
at both regional and systemic levels; these might include the control of dry
matter intake as a function of fundamental metabolic requirements of ruminants.
PMID- 24351980
TI - Porous platinum nanotubes modified with dendrimers as nanocarriers and
electrocatalysts for sensitive electrochemical aptasensors based on enzymatic
signal amplification.
AB - A highly sensitive electrochemical aptasensor for thrombin detection is developed
and demonstrated by using porous platinum nanotubes modified with polyamidoamine
dendrimers as nanocarriers and electrocatalysts. The proposed strategy affords a
low detection limit of 0.03 pM based on enzyme-based signal amplification.
PMID- 24351981
TI - Regularization design in penalized maximum-likelihood image reconstruction for
lesion detection in 3D PET.
AB - Detecting cancerous lesions is a major clinical application in emission
tomography. In previous work, we have studied penalized maximum-likelihood (PML)
image reconstruction for the detection task and proposed a method to design a
shift-invariant quadratic penalty function to maximize detectability of a lesion
at a known location in a two dimensional image. Here we extend the regularization
design to maximize detectability of lesions at unknown locations in fully 3D PET.
We used a multiview channelized Hotelling observer (mvCHO) to assess the lesion
detectability in 3D images to mimic the condition where a human observer examines
three orthogonal views of a 3D image for lesion detection. We derived simplified
theoretical expressions that allow fast prediction of the detectability of a 3D
lesion. The theoretical results were used to design the regularization in PML
reconstruction to improve lesion detectability. We conducted computer-based Monte
Carlo simulations to compare the optimized penalty with the conventional penalty
for detecting lesions of various sizes. Only true coincidence events were
simulated. Lesion detectability was also assessed by two human observers, whose
performances agree well with that of the mvCHO. Both the numerical observer and
human observer results showed a statistically significant improvement in lesion
detection by using the proposed penalty function compared to using the
conventional penalty function.
PMID- 24351983
TI - Insight and search in Katona's five-square problem.
AB - Insights are often productive outcomes of human thinking. We provide a cognitive
model that explains insight problem solving by the interplay of problem space
search and representational change, whereby the problem space is constrained or
relaxed based on the problem representation. By introducing different
experimental conditions that either constrained the initial search space or
helped solvers to initiate a representational change, we investigated the
interplay of problem space search and representational change in Katona's five
square problem. Testing 168 participants, we demonstrated that independent hints
relating to the initial search space and to representational change had little
effect on solution rates. However, providing both hints caused a significant
increase in solution rates. Our results show the interplay between problem space
search and representational change in insight problem solving: The initial
problem space can be so large that people fail to encounter impasse, but even
when representational change is achieved the resulting problem space can still
provide a major obstacle to finding the solution.
PMID- 24351984
TI - Lower pitch is larger, yet falling pitches shrink.
AB - Experiments using diverse paradigms, including speeded discrimination, indicate
that pitch and visually-perceived size interact perceptually, and that higher
pitch is congruent with smaller size. While nearly all of these studies used
static stimuli, here we examine the interaction of dynamic pitch and dynamic
size, using Garner's speeded discrimination paradigm. Experiment 1 examined the
interaction of continuous rise/fall in pitch and increase/decrease in object
size. Experiment 2 examined the interaction of static pitch and size (steady
high/low pitches and large/small visual objects), using an identical procedure.
Results indicate that static and dynamic auditory and visual stimuli interact in
opposite ways. While for static stimuli (Experiment 2), higher pitch is congruent
with smaller size (as suggested by earlier work), for dynamic stimuli (Experiment
1), ascending pitch is congruent with growing size, and descending pitch with
shrinking size. In addition, while static stimuli (Experiment 2) exhibit both
congruence and Garner effects, dynamic stimuli (Experiment 1) present congruence
effects without Garner interference, a pattern that is not consistent with
prevalent interpretations of Garner's paradigm. Our interpretation of these
results focuses on effects of within-trial changes on processing in dynamic tasks
and on the association of changes in apparent size with implied changes in
distance. Results suggest that static and dynamic stimuli can differ
substantially in their cross-modal mappings, and may rely on different processing
mechanisms.
PMID- 24351985
TI - Multimodal integration of time.
AB - Recent studies suggest that the accuracy of duration discrimination for visually
presented intervals is strongly impaired by concurrently presented auditory
intervals of different duration, but not vice versa. Because these studies rely
mostly on accuracy measures, it remains unclear whether this impairment results
from changes in perceived duration or rather from a decrease in perceptual
sensitivity. We therefore assessed complete psychometric functions in a duration
discrimination task to disentangle effects on perceived duration and sensitivity.
Specifically, participants compared two empty intervals marked by either visual
or auditory pulses. These pulses were either presented unimodally, or accompanied
by task-irrelevant pulses in the respective other modality, which defined
conflicting intervals of identical, shorter, or longer duration. Participants
were instructed to base their temporal judgments solely on the task-relevant
modality. Despite this instruction, perceived duration was clearly biased toward
the duration of the intervals marked in the task-irrelevant modality. This was
not only found for the discrimination of visual intervals, but also, to a lesser
extent, for the discrimination of auditory intervals. Discrimination sensitivity,
however, was similar between all multimodal conditions, and only improved
compared to the presentation of unimodal visual intervals. In a second
experiment, evidence for multisensory integration was even found when the task
irrelevant modality did not contain any duration information, thus excluding
noncompliant attention allocation as a basis of our results. Our results thus
suggest that audiovisual integration of temporally discrepant signals does not
impair discrimination sensitivity but rather alters perceived duration,
presumably by means of a temporal ventriloquism effect.
PMID- 24351982
TI - Structural insights into the role of the Smoothened cysteine-rich domain in
Hedgehog signalling.
AB - Smoothened (Smo) is a member of the Frizzled (FzD) class of G-protein-coupled
receptors (GPCRs), and functions as the key transducer in the Hedgehog (Hh)
signalling pathway. Smo has an extracellular cysteine-rich domain (CRD),
indispensable for its function and downstream Hh signalling. Despite its
essential role, the functional contribution of the CRD to Smo signalling has not
been clearly elucidated. However, given that the FzD CRD binds to the endogenous
Wnt ligand, it has been proposed that the Smo CRD may bind its own endogenous
ligand. Here we present the NMR solution structure of the Drosophila Smo CRD, and
describe interactions between the glucocorticoid budesonide (Bud) and the Smo
CRDs from both Drosophila and human. Our results highlight a function of the Smo
CRD, demonstrating its role in binding to small-molecule modulators.
PMID- 24351986
TI - Modeling the roles of category and feature information in inference.
AB - The goal of the current research is to use the experimental methods and
mathematical models of the information integration framework to precisely
determine how category and feature information are combined when making an
inference. In three experiments, participants were trained on a probabilistic
relationship between a category label and the presence of a property and,
separately, the relationship between a visual feature and the presence of the
property. Participants were then shown the category label alone, the feature
alone, or both in combination, and asked to infer the presence or absence of the
property. Two information integration models, the fuzzy logical model of
perception and the linear integration model, were fit to the data. The modeling
results show that participants were non-Bayesian in their combination of the two
sources of information, showed diversity in the relative weight placed on
category information, and consistently used each source of information to the
extent to which it was known.
PMID- 24351987
TI - Further evidence for a spatial-numerical association in children before formal
schooling.
AB - Given the robust finding that number and space are associated systematically at
least in school children and adults, it has been concluded that this association
might be based on the frequent practice of reading or writing skills, which are
usually consolidated by formal schooling. However, first studies contradict this
assumption demonstrating that associations of "small" magnitudes with left space
and of "large" magnitudes with right space exist already in preschoolers. The
present study used a non-symbolic magnitude comparison task to examine whether
kindergartners who have not yet been formally instructed in reading and writing
show a SNARC effect, that is, whether they would respond more rapidly with the
right hand to larger numbers and with the left hand to smaller numbers. This
assumption was confirmed by the data. In view of further evidence for an
association between number and space that evolves before children are proficient
in reading and writing, the role of potential alternative culture-specific,
individual, and universal foundations of this association is emphasized and
discussed.
PMID- 24351988
TI - Similarities in human visual and declared measures of preference for opposite-sex
faces.
AB - Facial appearance in humans is associated with attraction and mate choice.
Numerous studies have identified that adults display directional preferences for
certain facial traits including symmetry, averageness, and sexually dimorphic
traits. Typically, studies measuring human preference for these traits examine
declared (e.g., choice or ratings of attractiveness) or visual preferences (e.g.,
looking time) of participants. However, the extent to which visual and declared
preferences correspond remains relatively untested. In order to evaluate the
relationship between these measures we examined visual and declared preferences
displayed by men and women for opposite-sex faces manipulated across three
dimensions (symmetry, averageness, and masculinity) and compared preferences from
each method. Results indicated that participants displayed significant visual and
declared preferences for symmetrical, average, and appropriately sexually
dimorphic faces. We also found that declared and visual preferences correlated
weakly but significantly. These data indicate that visual and declared
preferences for manipulated facial stimuli produce similar directional
preferences across participants and are also correlated with one another within
participants. Both methods therefore may be considered appropriate to measure
human preferences. However, while both methods appear likely to generate similar
patterns of preference at the sample level, the weak nature of the correlation
between visual and declared preferences in our data suggests some caution in
assuming visual preferences are the same as declared preferences at the
individual level. Because there are positive and negative factors in both methods
for measuring preference, we suggest that a combined approach is most useful in
outlining population level preferences for traits.
PMID- 24351989
TI - Update on irritable bowel syndrome program of research.
AB - PURPOSE: This article provides an update and overview of a nursing research
program focused on understanding the pathophysiology and management of irritable
bowel syndrome (IBS). METHODS: This review includes English language papers from
the United States, Europe, and Asia (e.g., South Korea) from 1999 to 2013. We
addressed IBS as a health problem, emerging etiologies, diagnostic and treatment
approaches and the importance of a biopsychosocial model. RESULTS: IBS is a
chronic, functional gastrointestinal disorder characterized by recurrent episodes
of abdominal pain and alterations in bowel habit (diarrhea, constipation, mixed).
It is a condition for which adults, particularly women ages 20-45, seek health
care services in both the United States and South Korea. Clinically, nurses play
key roles in symptom prevention and management including designing and
implementing approaches to enhance the patients' self-management strategies.
Multiple mechanisms are believed to participate in the development and
maintenance of IBS symptoms including autonomic nervous system dysregulation,
intestinal inflammation, intestinal dysbiosis, dietary intolerances, alterations
in emotion regulation, heightened visceral pain sensitivity, hypothalamic
pituitary-adrenal dysregulation, and dysmotility. Because IBS tends to occur in
families, genetic factors may also contribute to the pathophysiology. Patients
with IBS often report a number of co-morbid disorders and/or symptoms including
poor sleep. CONCLUSION: The key to planning effective management strategies is to
understand the heterogeneity of this disorder. Interventions for IBS include non
pharmacological strategies such as cognitive behavior therapy, relaxation
strategies, and exclusion diets.
PMID- 24351990
TI - [A guide on the use of factor analysis in the assessment of construct validity].
AB - PURPOSE: The purpose of this study is to provide researchers with a simplified
approach to undertaking exploratory factor analysis for the assessment of
construct validity. METHODS: All articles published in 2010, 2011, and 2012 in
Journal of Korean Academy of Nursing were reviewed and other relevant books and
articles were chosen for the review. RESULTS: In this paper, the following were
discussed: preliminary analysis process of exploratory factor analysis to examine
the sample size, distribution of measured variables, correlation coefficient, and
results of KMO measure and Bartlett's test of sphericity. In addition, other
areas to be considered in using factor analysis are discussed, including
determination of the number of factors, the choice of rotation method or
extraction method of the factor structure, and the interpretation of the factor
loadings and explained variance. CONCLUSION: Content validity is the degree to
which elements of an assessment instrument are relevant to and representative of
the targeted construct for a particular assessment purpose. This measurement is
difficult and challenging and takes a lot of time. Factor analysis is considered
one of the strongest approaches to establishing construct validity and is the
most commonly used method for establishing construct validity measured by an
instrument.
PMID- 24351991
TI - [Risk factors for pediatric inpatient falls].
AB - PURPOSE: The purpose of this study was to identify risk factors for pediatric
inpatients falls. METHODS: The study was a matched case-control design. The
participants were 279 patients under the age of 6 who were admitted between
January 1, 2004 and December 31, 2009. Through chart reviews, 93 pediatric
patients who fell and 186 ones who did not fall were paired by gender, age,
diagnosis, and length of stay. Five experts evaluated the 38 fall risk factors
selected by the researchers. RESULTS: In a general hospital, pediatric patients
with secondary diagnosis, tests that need the patient to be moved, intravenous
lines, hyperactivity, anxiolytics, sedatives and hypnotics, and general
anesthetics showed significance for falls on adjusted-odds ratios. Conditional
logistic regression analysis was performed to elucidate the factors that
influence pediatric inpatient falls. The probability of falls increased with
hyperactivity and general weakness. Patients who didn't have tests that required
them to be moved and intravenous line had a higher risk of falls. CONCLUSION:
These findings provide information that is relevant in developing fall risk
assessment tools and prevention programs for pediatric inpatient falls.
PMID- 24351992
TI - [Effects of nurses' mentoring on turnover intention: focused on the mediating
effects role stress and burnout].
AB - PURPOSE: The purpose of this study was to investigate the casual relationship
between nurses' mentoring and turnover intention and to verify the goodness of
fit between a hypothetical model and actual data in order to suggest an adequate
model. METHODS: The survey was conducted with 434 nurses working in general
hospitals in Seoul. Data were collected during February 2013, and analyzed with
SPSS Windows 18.0 and AMOS 7.0. RESULTS: Mentoring was found to have a direct
effect on decrease in role stress. Role stress had a direct effect on increase in
burnout and mentoring, with role stress as a mediator, there was an indirect
effect on burnout. Burnout had a direct effect on increase in turnover intention,
and role stress, with burnout as a mediator, and mentoring, through role stress
and burnout, an indirect effect was found on increase in turnover intention.
CONCLUSION: The results of this study indicate that nursing managers should put
effort into reducing role stress and burnout, while seeking to establish a more
efficient mentoring system so that for nurses, there will be a lowering of
turnover intention.
PMID- 24351993
TI - [Effects of a fall prevention program on falls in frail elders living at home in
rural communities].
AB - PURPOSE: This study was conducted to determine the effects of a fall prevention
program on falls, physical function, psychological function, and home
environmental safety in frail elders living at home in rural communities.
METHODS: The design of this study was a nonequivalent control group pre posttest
design. The study was conducted from July to November, 2012 with 30 participants
in the experimental group and 30 in the control group. Participants were
registered at the public health center of E County. The prevention program on
falls consisted of laughter therapy, exercise, foot care and education. The
program was provided once a week for 8 weeks and each session lasted 80 minutes.
RESULTS: The risk score for falls and depression in the experimental group
decreased significantly compared with scores for the control group. Compliance
with prevention behavior related to falls, knowledge score on falls, safety
scores of home environment, physical balance, muscle strength of lower
extremities, and self-efficacy for fall prevention significantly increased in the
experimental group compared with the control group. CONCLUSION: These results
suggest that the prevention program on falls is effective for the prevention of
falls in frail elders living at home.
PMID- 24351994
TI - [Effects of a cultural competence promotion program for multicultural maternity
nursing care: case-based small group learning].
AB - PURPOSE: The purpose of this study was to examine the effects of a cultural
competence improvement program for maternity nurses. METHODS: A quasi
experimental study using a non-equivalent control group pre and posttest design
was used. Participants were 67 maternity nurses caring for multicultural pregnant
women in G city. The cultural competence improvement program was developed based
on the 3-D Puzzle Model and was provided using case-based small group learning
methods for the experimental group (n=31). The control group (n=36) did not
receive any intervention. Data were collected using self-report structured
questionnaires at two time points: prior to the intervention and after the
intervention and were analyzed with descriptive statistics, chi2-test, and t
test. RESULTS: Compared to the control group, the experimental group reported
significant positive changes for cultural knowledge (t=6.39, p<.001), cultural
awareness (t=3.50, p<.001), and cultural acceptance (t=4.08, p<.001). However,
change in cultural nursing behaviors (t=0.92, p=.067) was not significantly
different between the two groups. CONCLUSION: Findings from this study indicate
that a cultural competence improvement program with case-based small group
learning is a useful intervention strategy to promote multicultural maternity
care. Further, strategies to improve cultural nursing behavior should be
developed to promote culturally congruent nursing care.
PMID- 24351995
TI - [Health-illness transition of patients with Young-Onset Parkinson's Disease].
AB - PURPOSE: The purpose of this study was to explore the health-illness transition
of patients with Young-Onset Parkinson's Disease (YOPD). METHODS: From June to
November 2011, 17 patients with YOPD who visited a neurologic clinic in a
tertiary hospital participated in the study. Data were collected through in-depth
interviews and analyzed using the grounded theory of Strauss and Corbin. RESULTS:
The core category of the participants' health-illness transition emerged as
'reshaping identity following uncontrollable changes'. The participants' health
illness transition process consisted of six phases in sequence: ego withdrawal,
loss of role, frustration, change of thought, modification of life tract, and
second life. Although most participants proceeded through the six phases
chronologically, some returned to the frustration phase and then took up the
remaining phases. CONCLUSION: The study results provide an in-depth understanding
of health-illness transition experiences in the participants. These findings
suggest a need to develop appropriate nursing intervention strategies according
to the different phases in the health-illness transition of patients with YOPD.
PMID- 24351996
TI - [Effectiveness of enneagram group counseling for self-identification and
depression in nursing college students].
AB - PURPOSE: The purpose of this study was to examine effects of enneagram group
counseling program on self-identification and depression in nursing college
students. Three groups, categorized by how the students solve their conflicts,
were selected to identify changes from the program. METHODS: A quasi-experimental
study with a non-equivalent control group and pre posttest design was used.
Participants were assigned to the experimental group (n=30) or control group
(n=33). The experimental group participated in enneagram group counseling program
for 38 hours through eight sessions covering four different topics. Collected
data were analyzed using Chi-square test, Fisher's exact test, t-test, and
Wilcoxon signed rank test. RESULTS: Total self-identity score for the
experimental group was significantly higher than the control group. However,
there was no significant difference between the two groups for depression scores.
The Assertive and Compliant groups demonstrated significant change in self
identification while the Withdrawn groups did not reveal any change. CONCLUSION:
Results indicate that the enneagram group counseling program is very effective in
establishing positive self-identification for nursing college students who face
developmental crisis and stressful situations. It is also expected that this
program would be useful to enhance the students' confidence through a deeper
understanding and acceptance of themselves.
PMID- 24351997
TI - [Meta-analysis of psychosocial interventions to reduce pain in patients with
cancer].
AB - PURPOSE: The purpose of this study was to investigate the effects of psychosocial
interventions on pain in cancer patients. METHODS: Eight studies published
between 1980 and 2012 in Korean and ten studies published between 2002 and 2012
in English met the inclusion criteria with a total of 1539 participants.
Methodological quality assessed by Cochrane's Risk of Bias for randomized studies
and Risk of Bias Assessment tool for non randomized studies. The data were
analyzed by the RevMan 5.2 program of Cochrane library. RESULTS: Overall, study
quality was moderate to high. Effect sizes were heterogeneous and subgroup
analysis was done. Cognitive behavioral therapy (CBT) were effective for pain
(ES= -0.35; 95% CI= -0.56, -0.13). Pain education studies measured with NRS and
VAS were effective for pain (ES= -0.77; 95% CI= -1.01, -0.52). Publication bias
was not detected. CONCLUSION: This study support the use of psychosocial
interventions administered to cancer patients for their pain management. However,
more well-designed studies are needed.
PMID- 24351998
TI - [The process of acceptance of complementary and alternative therapies (CATs)
among nurses: grounded theory approach].
AB - PURPOSE: This study was done to explore the process of accepting CATs among
nurses who experienced CATs in Korea. METHODS: Grounded theory methodology was
utilized. Data were collected from 10 nurses during individual in-depth
interviews. Theoretical sampling was used until the data reached saturation. Data
were analyzed using the constant comparative analysis method. RESULTS: The core
category emerged as "resolving the doubt and integrating" explaining the process
of accepting CATs. The nurses engaged in three stages: need awareness, look for
solution and integration. Causal conditions were interest as a nursing
intervention and orthodox medical limitations. Context was lack of basis for
application and increase in social interest. Strategies were new knowledge
acquisition, having a strong will, combined with existing knowledge, and
individualized intervention. Intervening conditions were others' eye, exhaustion
for nurses and physical environment. Consequences were expanding of the nursing
role and improved nurse satisfaction. CONCLUSION: The results of the study should
facilitate application of CATs in nursing practice. To help nurses who are
interested in CATs, there is a need for education programs, and further research
on CATs.
PMID- 24351999
TI - [Effect of PLISSIT model sexual health enhancement program for women with
gynecologic cancer and their husbands].
AB - PURPOSE: The purpose of this study was to examine effects of the Permission,
Limited Information, Specific Suggestions, Intensive Therapy (PLISSIT) model
sexual health enhancement program on, and development in, sexual function, sexual
distress, marital intimacy, and subjective happiness of women with gynecologic
cancer and their husbands. METHODS: The comprehensive program (4 session, 90
minutes per session) was developed based on the PLISSIT model. Participants were
43 couples, 21 assigned to the experimental group who attended the 4-week
program, and 22 to the control group. Sexual function, sexual distress, marital
intimacy, subjective happiness of the women, marital intimacy, subjective
happiness of husbands were determined by a questionnaire that was completed by
the participants before and after the program. The control group received the
intervention post experiment. Chi-square test, t-test, Fisher's exact test were
used to test the effectiveness of the program. RESULTS: Post intervention results
showed significant differences between the groups for sexual function, sexual
distress, and marital intimacy in the women and for subjective happiness in the
husbands. CONCLUSION: Results indicate that the sexual health enhancement program
is effective in improving sexual function, lowering sexual distress, increasing
marital intimacy, and subjective happiness in women with gynecologic cancer and
their husbands.
PMID- 24352000
TI - [Effects of a multicultural education program on the cultural competence, empathy
and self-efficacy of nursing students].
AB - PURPOSE: This study was done to examine the effects of a multicultural education
program on nursing students' cultural competence, empathy, and self-efficacy.
METHODS: In this quasi-experimental study, the participants were assigned to an
experimental group (n=40) or a control group (n=40). The data were analyzed using
independent t-test, Chi-square or Fisher's exact test, and paired t-test with the
SPSS windows 18.0 program. RESULTS: After receiving the multicultural education
program, the levels of cultural competence and self-efficacy in the experimental
group were higher than in the control group. The level of empathy increased
slightly in the experimental group while it decreased in the control group.
CONCLUSION: The results of this study indicate that multicultural education is
effective in raising the level of cultural competence and self-efficacy in
nursing students. Thus, there is a need for continuous effort to integrate
multicultural education programs in the nursing curriculum. Repeated study to
test effects of these multicultural education programs should be also necessary.
PMID- 24352001
TI - Confounding by linkage disequilibrium.
PMID- 24352002
TI - Significant association between CYP3A5 polymorphism and blood concentration of
tacrolimus in patients with connective tissue diseases.
AB - Although the association between CYP3A5 polymorphism and blood concentration of
tacrolimus (TAC) in patients with solid organ transplantation was established,
whether the association is also true in patients with connective tissue disease
(CTD) who usually receive small amount of TAC is uncertain. Here, we performed a
quantitative linear regression analysis to address the association between CYP3A5
and blood TAC concentration in patients with CTD. A total of 72 patients with CTD
were recruited in the current study and genotyped for rs776746 in CYP3A5, which
showed strong association with TAC concentration in patients with solid organ
transplantation. The blood trough concentration of TAC after taking 3 mg per day
was retrospectively obtained for each patient. As a result, allele A of rs776746
showed a significant association with a decreasing blood concentration of TAC
(P=0.0038). Those who are carrying at least one copy of the A allele displayed
decreased mean concentration of TAC by 31.0% compared with subjects with GG
genotype. Rs776746 is associated with concentrations of TAC in patients with CTD.
PMID- 24352003
TI - Metagenomic analysis reveals significant changes of microbial compositions and
protective functions during drinking water treatment.
AB - The metagenomic approach was applied to characterize variations of microbial
structure and functions in raw (RW) and treated water (TW) in a drinking water
treatment plant (DWTP) at Pearl River Delta, China. Microbial structure was
significantly influenced by the treatment processes, shifting from
Gammaproteobacteria and Betaproteobacteria in RW to Alphaproteobacteria in TW.
Further functional analysis indicated the basic metabolic functions of
microorganisms in TW did not vary considerably. However, protective functions,
i.e. glutathione synthesis genes in 'oxidative stress' and 'detoxification'
subsystems, significantly increased, revealing the surviving bacteria may have
higher chlorine resistance. Similar results were also found in glutathione
metabolism pathway, which identified the major reaction for glutathione synthesis
and supported more genes for glutathione metabolism existed in TW. This
metagenomic study largely enhanced our knowledge about the influences of
treatment processes, especially chlorination, on bacterial community structure
and protective functions (e.g. glutathione metabolism) in ecosystems of DWTPs.
PMID- 24352004
TI - Self-reported health parameters compared with clinician measurements: methods in
practice-based research.
AB - CONTEXT: Self-reported health data are used by health insurance companies to
assess risk. Most studies show underreporting compared with clinical
measurements. OBJECTIVE: To compare self-reported height, weight, blood pressure,
waist circumference, and dietary intake with registered dietitian's (RD's)
measures of the same parameters. DESIGN: This is a secondary analysis of data
collected in a larger study on the benefits of Medical Nutrition Therapy from an
RD for overweight and obese patients when provided free of charge through an
insurance benefit. SETTING: Participants completed a health risk assessment
survey at home, from which the self-reported measures were extracted. The
clinical measurements were taken by an RD in the office during a visit for
Medical Nutrition Therapy. PARTICIPANTS: Participants were 81.4% female, with a
mean body mass index of 35.0. All were insured and had a least 1 visit with an
RD. MAIN OUTCOME MEASURE(S): Main outcomes were correlation between self-reported
and RD-measured height, weight, body mass index, blood pressure, and waist
circumference. Blood pressure was categorized as normal or high and the kappa
statistic was used to examine category agreement between the 2 measures. Servings
of food groups were compared between the 2 measures by examining cumulative
percent within 0, 1, or 2 servings of the RD-measured value. RESULTS: The 2
measures of height and weight were highly correlated (0.974 and 0.986,
respectively). Blood pressure was more weakly correlated and when categorized had
low kappa scores, as did servings of food groups. CONCLUSIONS: Height and weight
were more closely correlated than in previous studies. In an insured population
enrolled in a weight management program, self-reported measures may be accurate
for determining program impact. Blood pressure may be better collected
categorically than continuously. The necessity of food intake assessment on a
risk assessment should be reconsidered.
PMID- 24352005
TI - Clinical features, developmental course, and psychiatric comorbidity of adult
autism spectrum disorders.
AB - Autism spectrum disorders (ASDs) include a heterogeneous group of
neurodevelopmental disorders with early onset in childhood. ASDs should be
considered lifelong clinical entities, although there is a certain variability in
developmental trajectories, and therefore should be considered of great interest
also for adulthood psychiatrists. A few studies have been carried out to explore
the clinical picture and course development of these disorders during adulthood,
or their relationship with other mental disorders. Indeed, ASDs often share
overlapping features with other disorders, such as schizophrenia and obsessive
compulsive, mood, and personality disorders, and as a result misdiagnoses often
occur. The aim of this review is to summarize the available literature on ASDs in
adulthood with a specific focus on the clinical picture, course, and psychiatric
comorbidity. It is proposed that a careful diagnostic screening for ASDs in
adults would contribute to clarifying the relationship with comorbid psychiatric
disorders, while improving the possibility of treatment and outcome of such
conditions.
PMID- 24352006
TI - In vitro action of flavonoids in the canine malignant histiocytic cell line DH82.
AB - Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of
death due to the lack of effective drugs. Flavonoids possess antioxidant, anti
inflammatory and anticarcinogenic properties and have been studied as
chemopreventive agents in human cancer therapy. However, the literature on dogs
is sparse. In this study, we analyzed the effect of nine flavonoids on cell
viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor
cell line (DH82). Apigenin, luteolin, trans-chalcone and 4-methoxychalcone showed
the highest degree of cytotoxicity in the absence of considerable DNA damage,
whereas genistein exhibited low cytotoxicity but induced a high level of DNA
damage. These five flavonoids inhibited topoisomerase IIa and IIb gene expression
to variable extents and with variable specificity. Genistein exerted a lower
inhibitory effect on the two topoisomerases than luteolin and apigenin. trans
Chalcone and 4-methoxychalcone exerted greater inhibition of topoisomerase IIa
expression than topoisomerase IIb. The differences in the effects between
genistein and luteolin and apigenin might be explained by the position of ring B,
whereas the more specific effect of chalcones on topoisomerase IIa might be due
to their open chain structure.
PMID- 24352007
TI - Effect of delayed icing on biogenic amines formation and bacterial contribution
of iced common carp (Cyprinus carpio).
AB - The variation of six biogenic amines (BAs) and total viable count (TVC) in common
carp (Cyprinus carpio) stored in ice with 0, 4 and 8 h delay before icing was
evaluated in a period of 4 days. Delayed icing led to significant (p < 0.05)
increases in TVC throughout the period of storage and showed a good correlation
with BAs content. The obtained data showed that putrescine and cadaverine were
predominant in all samples and it was indicated that they could be proper
indicators to determine the carp quality. Spermidine and spermine increased
slightly toward the end of storage and the levels of dangerous BAs (histamine and
tyramine) were under the limit over the period. As a result, it is indicated that
delaying time affects on formation of BAs and the effect in samples with 8 h
delay was significantly (p < 0.05) more than those with 0 and 4 h delay.
PMID- 24352008
TI - Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of
collagen synthesis and its therapeutic efficacy in osteoporotic bone by back
scattered electron imaging and microarchitecture analysis.
AB - Collagen hydrolysate (CH) has been reported to exhibit a positive effect on bone.
In the present study, the in vitro effects of CH (<3 kDa) were examined and the
in vivo experiments confirmed the positive effects of CH in ovariectomized (OVX)
rats. Bone mineral density (BMD) was examined by DXA analysis. Scanning electron
microscopic analysis and quantitative 3D-color backscattered electrons imaging
analysis were performed on the lumbar vertebrae. CH increased osteoblastic cell
proliferation and alkaline phosphatase activity in a dose-dependent manner.
Collagen synthesis and collagen, type1, alpha1 (COL1A1) gene expression were also
increased by CH treatment. Furthermore, CH-induced COL1A1 gene expression was
completely abolished by extracellular signal-regulated kinase (ERK) inhibitor,
suggesting the involvement of ERK/MAPK signaling for transcriptional effects on
COL1A1 expression. OVX rats supplemented with CH showed osteoprotective effects
as the BMD levels were increased compared with control. Moreover, CH prevented
the trabecular bone loss induced by OVX and improved the microarchitecture of
lumbar vertebrae. CH administration dose-dependently reduced the serum
procollagen type I N-terminal propeptide level, which was elevated by OVX. The
present study suggests that CH isolated in this study is a promising alternative
to current therapeutic agents for the management of osteoporosis.
PMID- 24352009
TI - Preparative separation of six rhynchophylla alkaloids from Uncaria macrophylla
wall by pH-zone refining counter-current chromatography.
AB - pH-Zone refining counter-current chromatography was successfully applied to the
preparative isolation and purification of six alkaloids from the ethanol extracts
of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%,
w/w) in U. macrophylla Wall, the target compounds were enriched by pH-zone
refining counter-current chromatography using a two-phase solvent system composed
of petroleum ether-ethyl acetate-isopropanol-water (2:6:3:9, v/v), adding 10 mM
triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous
mobile phase. Then pH-zone refining counter-current chromatography using the
other two-phase solvent system was used for final purification. Six target
compounds were finally isolated and purified by following two-phase solvent
system composed of methyl tert-butyl ether (MTBE)-acetonitrile-water (4:0.5:5,
v/v), adding triethylamine (TEA) (10 mM) to the organic phase and HCl (5 mM) to
aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36
mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg
rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified
by HPLC Their structures were identified by electrospray ionization-mass
spectrometry (ESI-MS) and 1H-NMR spectroscopy.
PMID- 24352010
TI - The effect of conformational variability of phosphotriesterase upon N-acyl-L
homoserine lactone and paraoxon binding: insights from molecular dynamics
studies.
AB - The organophosphorous hydrolase (PTE) from Brevundimonas diminuta is capable of
degrading extremely toxic organophosphorous compounds with a high catalytic
turnover and broad substrate specificity. Although the natural substrate for PTE
is unknown, its loop remodeling (loop 7-2/H254R) led to the emergence of a
homoserine lactonase (HSL) activity that is undetectable in PTE (kcat/km values
of up to 2 * 10(4)), with only a minor decrease in PTE paraoxonase activity. In
this study, homology modeling and molecular dynamics simulations have been
undertaken seeking to explain the reason for the substrate specificity for the
wild-type and the loop 7-2/H254R variant. The cavity volume estimated results
showed that the active pocket of the variant was almost two fold larger than that
of the wild-type (WT) enzyme. pKa calculations for the enzyme (the WT and the
variant) showed a significant pKa shift from WT standard values (DeltapKa = 3.5
units) for the His254 residue (in the Arg254 variant). Molecular dynamics
simulations indicated that the displacement of loops 6 and 7 over the active site
in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL) with
a large aliphatic chain to site in the channels easily. Thence the expanding of
the active pocket is beneficial to C4-HSL binding and has a little effect on
paraoxon binding. Our results provide a new theoretical contribution of loop
remodeling to the rapid divergence of new enzyme functions.
PMID- 24352011
TI - Seed germination-influencing bioactive secondary metabolites secreted by the
endophyte Cladosporium cladosporioides LWL5.
AB - The present study was aimed to isolate bioactive metabolites produced by a fungal
endophyte from Helianthus annuus, Capsicum annuum, and Cucumis sativus and to
assess their role in seed germination. Culture filtrate of the endophyte HA-3B
from H. annuus was significantly inhibitory towards the germination and growth of
lettuce seeds. HA-3B was identified as Cladosporium cladosporioides LWL5 through
molecular techniques. Different concentrations (100, 500 and 1000 ppm) of the
ethyl acetate extract obtained from the culture inhibited the lettuce seed
germination. The extract was subjected to column chromatography and a bioassay
guided isolation method, which yielded compounds 1, 2 and an oily fraction. The
oily fraction, subjected to fractionation and spectroscopic techniques, resulted
in the identification of 31 different constituents. Compounds 1 and 2 were
identified and characterized through MS and NMR spectroscopic techniques as
benzoic acid. The bioassay results showed that this compound significantly
inhibited the growth and germination of lettuce seeds. In conclusion, assessing
the role of endophytes harboring essential crop plants can help us to develop
potentially eco-friendly herbicides.
PMID- 24352012
TI - Synthesis of delta-oxo-1,1-bis(triflyl)alkanes and their acidities.
AB - The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable
carbonyls yielded delta-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities
in both the gas and solution phases were determined.
PMID- 24352013
TI - Stereocontrolled synthesis and functionalization of cyclobutanes and
cyclobutanones.
AB - In the last decade a certain number of new cyclobutane and cyclobutanone
synthesis and functionalization protocols have been published. Organo- and
biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have
been developed with interesting results. Also, successful new total synthesis of
bioactive compounds and drugs have been recently reported where a four membered
ring represented the key intermediate. Therefore, the rising interest in this
field represents a great point of discussion for the scientific community,
disclosing the synthetic potential of strained four membered ring carbocyclic
compounds. Herein we report a critical survey on the literature concerning the
enantiocontrolled synthesis and functionalization of cyclobutane derivatives,
with particular attention to metal-free, low impact methodologies, published
during the period 2000-2013.
PMID- 24352014
TI - Beads-based electrochemical assay for the detection of influenza hemagglutinin
labeled with CdTe quantum dots.
AB - In this study we describe a beads-based assay for rapid, sensitive and specific
isolation and detection of influenza vaccine hemagglutinin (HA). Amplification of
the hemagglutinin signal resulted from binding of an electrochemical label as
quantum dots (QDs). For detection of the metal and protein part of the resulting
HA-CdTe complex, two differential pulse voltammetric methods were used. The
procedure includes automated robotic isolation and electrochemical analysis of
the isolated product. The isolation procedure was based on the binding of
paramagnetic particles (MPs) with glycan (Gly), where glycan was used as the
specific receptor for linkage of the QD-labeled hemagglutinin.
PMID- 24352015
TI - Antimicrobial and antioxidant activities and effect of 1-hexadecene addition on
palmarumycin C2 and C3 yields in liquid culture of endophytic fungus Berkleasmium
sp. Dzf12.
AB - Two spirobisnaphthalenes, namely palmarumycins C2 and C3, were isolated from
cultures of the endophytic fungus Berkleasmium sp. Dzf12 after treatment with 1
hexadecene. After addition of 1-hexadecene at 10% to the medium on day 6 of
culture, the maximal yields of palmarumycins C2 and C3 were obtained as 0.40 g/L
and 1.19 g/L, which were 40.00 fold and 59.50 fold higher, respectively, in
comparison with those of the control (0.01 g/L and 0.02 g/L). The results
indicated that addition of 1-hexadecene can be an effective strategy for
enhancing the production of palmarumycins C2 and C3 in liquid culture of
endophytic fungus Berkleasmium sp. Dzf12. Palmarumycin C3 exhibited stronger
antimicrobial and antioxidant activities than palmarumycin C2.
PMID- 24352016
TI - In vitro evaluation of novel inhibitors against the NS2B-NS3 protease of dengue
fever virus type 4.
AB - The discovery of potent therapeutic compounds against dengue virus is urgently
needed. The NS2B-NS3 protease (NS2B-NS3pro) of dengue fever virus carries out all
enzymatic activities needed for polyprotein processing and is considered to be
amenable to antiviral inhibition by analogy. Virtual screening of 300,000
compounds using Autodock 3 on the GVSS platform was conducted to identify novel
inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in
vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel
compounds were identified as inhibitors with IC50 values of 3.9 +/- 0.6-86.7 +/-
3.6 MUM. Three strong NS2B-NS3pro inhibitors were further confirmed as
competitive inhibitors with Ki values of 4.0 +/- 0.4, 4.9 +/- 0.3, and 3.4 +/-
0.1 MUM, respectively. Hydrophobic and hydrogen bond interactions between amino
acid residues in the NS3pro active site with inhibition compounds were also
identified.
PMID- 24352017
TI - Total synthesis of six 3,4-unsubstituted coumarins.
AB - In this article we describe a new methodology for the total synthesis of 3,4
unsubstituted coumarins from commercially available starting materials. Six
examples were prepared, including five naturally occurring coumarins--7-hydroxy
6,8-dimethoxy-coumarin (isofraxidin), 7-hydroxy-6-methoxycoumarin (scopoletin),
6,7,8-trimethoxy-coumarin, 6,7-dimethoxycoumarin (scoparone), and 7,8
dihydroxycoumarin (daphnetin) and one synthetic coumarin, 7-hydroxy-6
ethoxycoumarin. Moreover, five important o-hydroxybenzaldehyde intermediates were
also obtained, namely 2,4-dihydroxy-3,5-dimethoxybenzaldehyde, 2,4-dihydroxy-5
methoxybenzaldehyde, 5-ethoxy-2,4-dihydroxy-benzaldehyde, 2-hydroxy-3,4,5
trimethoxybenzaldehyde, and 2-hydroxy-4,5-dimethoxy-benzaldehyde. The method
developed herein involves just three or four steps and allows for the rapid
synthesis of these important molecules in excellent yields. This is the first
synthesis of 6,7,8-trimethoxycoumarin and 7-hydroxy-6-ethoxycoumarin.
PMID- 24352018
TI - Modulation of lipogenesis and glucose consumption in HepG2 cells and C2C12
myotubes by sophoricoside.
AB - Sophoricoside, an isoflavone glycoside isolated from Sophora japonica
(Leguminosae), has been widely reported as an immunomodulator. In this study, the
effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells
and C2C12 myotubes were investigated. Treatment with sophoricoside at
concentrations of 1-10 MUM inhibited lipid accumulation in HepG2 cells in a dose
dependent manner. At the same concentration range, no effect on cell viability
was observed in the MTT assay. Inhibition of lipogenesis was associated with the
downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes
(FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering
effect was mediated via the phosphorylation of AMPK. Further investigation of the
activities of this isoflavone showed that sophoricoside has the capability to
increase glucose uptake by C2C12 myotubes. It also effectively inhibited the
activities of alpha-glucosidase and alpha-amylase in vitro and remarkably lowered
postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest
that sophoricoside is an effective regulator of lipogenesis and glucose
consumption and may find utility in the treatment of obesity and type 2 diabetes.
PMID- 24352019
TI - Vascular aldosterone production at the pre-diabetic stage of young Otsuka Long
Evans Tokushima Fatty (OLETF) rats, compared with Long-Evans Tokushima Otsuka
(LETO) rats.
AB - We examined the ability of aortic smooth muscle cells (AoSMC) prepared from
spontaneously diabetic rats to produce aldosterone (Aldo) and the regulatory
mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans
Tokushima Otsuka (LETO: the control group) and 6 week-old Otsuka Long-Evans
Tokushima Fatty (OLETF: the type 2 diabetes group) rats were used in the present
experiments. CYP11B2 (Aldo synthetase) mRNA expression was detected in both the
LETO and OLETF AoSMC. Basal Aldo production was significantly greater (4-5 fold
higher) in the OLETF AoSMC culture medium than in the LETO AoSMC culture medium.
When AoSMC were co-incubated with high-density lipoproteins (HDL), supplying
cholesterol as a substrate for steroidogenesis in rats, angiotensin II (AII)
significantly increased greater Aldo production in the OLETF AoSMC than in the
LETO AoSMC. The present data suggested that future onset of diabetic vascular
dysfunction is partly caused by excess Aldo production by AoSMC in young OLETF
rats. Concomitant stimulation by HDL and AII resulted in elevated Aldo production
in the OLETF and the LETO AoSMC, and also demonstrated that AII-induced Aldo
production is greatly enhanced by HDL in OLETF, rather than in LETO. In
conclusion, our data clearly demonstrated that Aldo production in the OLETF AoSMC
was significantly higher than in the LETO AoSMC, suggesting possible future onset
of vascular dysfunction in diabetes, induced by local Aldo production in the
AoSMC.
PMID- 24352020
TI - Preparative isolation and purification of five flavonoid glycosides and one
benzophenone galloyl glycoside from Psidium guajava by high-speed counter-current
chromatography (HSCCC).
AB - Psidium guajava leaves have a diverse phytochemical composition including
flavonoids, phenolics, meroterpenoids and triterpenes, responsible for the
biological activities of the medicinal parts. In particular, flavonol glycosides
show beneficial effects on type II diabetes mellitus. A simple and efficient
HSCCC method has been developed for the preparative separation of five flavonoid
glycosides and one diphenylmethane glycoside from P. guajava. A solvent system
composed of n-hexane-ethyl acetate-methanol-water (0.7:4:0.8:4, v/v/v/v) was
optimized for the separation. The upper phase was used as the stationary phase,
and the lower phase was used as the mobile phase. Under the optimized conditions,
hyperoside (15.3 mg), isoquercitrin (21.1 mg), reynoutrin (65.2 mg), quercetin-3
O-beta-D-arabinopyranoside (71.7 mg), quercetin-3-O-alpha-L-arabinofuranoside
(105.6 mg) and 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6''-O-galloyl)-beta
D-glucopyranoside (98.4 mg) were separated from crude sample (19.8 g). The
structures of all the isolates were identified by ESI-MS, 1H- and 13C-NMR
analyses and their purities (>95%) were determined using HPLC.
PMID- 24352022
TI - Characterization of the nutraceutical quality and antioxidant activity in bell
pepper in response to grafting.
AB - The grafting of fruits and vegetables influences fruit quality. The aim of the
present work was to assess the effect of the rootstock and the scion on the
antioxidant activity and the content in vitamin C, total phenols, lycopene and
beta-carotene of bell pepper. The cultivars Fascinato and Jeanette were used as
scion and Terrano was used as rootstock. Four harvests in the production cycle of
the vegetable were analyzed in a cultivation system under shading nets. The
results indicate statistical differences in the content of these bioactive
compounds between the varieties, between grafting and not grafting and between
sampling dates (p <= 0.05). The vitamin C content, beta-carotene, and antioxidant
capacity proved significantly higher in Fascinato than in Janette. On average,
grafting increased beta-carotene and vitamin C concentrations and improved the
antioxidant capacity, but had no influence on the total phenol or lycopene
contents. It is concluded that grafting to the rootstock Terrano improves the
nutritional quality of the fruit produced in both varieties of bell pepper
studied.
PMID- 24352021
TI - Stimulation of natural killer T cells by glycolipids.
AB - Natural killer T (NKT) cells are a subset of T cells that recognize glycolipid
antigens presented by the CD1d protein. The initial discovery of
immunostimulatory glycolipids from a marine sponge and the T cells that respond
to the compounds has led to extensive research by chemists and immunologists to
understand how glycolipids are recognized, possible responses by NKT cells, and
the structural features of glycolipids necessary for stimulatory activity. The
presence of this cell type in humans and most mammals suggests that it plays
critical roles in antigen recognition and the interface between innate and
adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells
have been identified, and it is likely that glycolipid antigens remain to be
discovered. Multiple series of structurally varied glycolipids have been
synthesized and tested for stimulatory activity. The structural features of
glycolipids necessary for NKT cell stimulation are moderately well understood,
and designed compounds have proven to be much more potent antigens than their
natural counterparts. Nevertheless, control over NKT cell responses by designed
glycolipids has not been optimized, and further research will be required to
fully reveal the therapeutic potential of this cell type.
PMID- 24352023
TI - An efficient approach to the synthesis of highly congested 9,10
dihydrophenanthrene-2,4-dicarbonitriles and their biological evaluation as
antimicrobial agents.
AB - An efficient and novel method for the synthesis in moderate to good yield (72%
84%) of a series of 3-amino-1-substituted-9,10-dihydrophenanthrene-2,4
dicarbonitriles 1-5 via one-pot multi-component reactions of aldehydes,
malononitrile, 1-tetralone and ammonium acetate has been delineated.
Cyclocondensation attempts of aminocyanophenanthrene derivatives 1, 2, 4 and 5
with acetic anhydride in the presence of conc. H2SO4 failed and instead the
diacetylamino derivatives 10-13 were obtained. All prepared compounds were
structurally elucidated by various spectroscopic methods and X-ray
crystallography. N,N-diacetylamino-derivatives of phenanthrene have shown good
antimicrobial activity.
PMID- 24352024
TI - Synthesis of dimethyl aryl acylsulfonium bromides from aryl methyl ketones in a
DMSO-HBr system.
AB - A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts
has been developed. A series of dimethyl aryl acylsulfonium bromides were
prepared by the reaction of aryl methyl ketones with hydrobromic acid and
dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production
and the bromination reaction take place in the DMSO-HBr oxidation system. What's
more, it is also a key intermediate for the synthesis of arylglyoxals.
PMID- 24352025
TI - Madecassoside inhibits melanin synthesis by blocking ultraviolet-induced
inflammation.
AB - Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.),
is used as a therapeutic agent in wound healing and also as an anti-inflammatory
and anti-aging agent. However, the involvement of MA in skin-pigmentation has not
been reported. This study was conducted to investigate the effects of MA on
ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of
keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin
synthesis and melanosome transfer in the co-culture system. These effects were
further demonstrated by the MA-induced inhibition of protease-activated receptor
2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and
prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was
confirmed on artificially tanned human skin. MA significantly reduced UV-induced
melanin index at 8 weeks after topical application. Overall, the study
demonstrated significant benefits of MA use in the inhibition of
hyperpigmentation caused by UV irradiation.
PMID- 24352026
TI - Crystal structures and antifungal activities of fluorine-containing thioureido
complexes with nickel(II).
AB - Ni(II) complexes with N-2-fluorobenzoylpiperidine-1-carbothioimidate (L2-), N-4
fluorobenzoylpiperidine-1-carbothioimidate (L3-), N-2-fluorobenzoylmorpholine- 1
carbothioimidate (L5-) and N-4-fluorobenzoylmorpholine-1-carbothioimidate (L6-)
have been synthesized and characterized by elemental analysis, FTIR and 1H-NMR.
The crystal structures of three ligands (HL2, HL3 and HL6) and the corresponding
Ni(II) complexes ([Ni(L2)2], [Ni(L3)2] and [Ni(L6)2]) have been determined by X
ray diffraction. The antifungal activities of the Ni(II) complexes together and
the corresponding ligands against the fungi Botrytis cinerea, Trichoderma spp.,
Myrothecium and Verticillium spp. have been investigated. The experimental
results showed that the ligands and their complexes have antifungal abilities.
When the fluorine was substituted on the para-benzoyl moiety, the antifungal
activity of the ligands was obviously increased. Moreover, the ligands were
stronger than their complexes in inhibiting fungal activities. The antifungal
ability of HL6 is especially strong, and similar to that of the commercial
fungicide fluconazole.
PMID- 24352027
TI - Design, synthesis and evaluation of N13-substituted evodiamine derivatives
against human cancer cell lines.
AB - Attempting to improve the anticancer activity and solubility of evodiamine in
simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions,
thirty-eight N13-substituted evodiamine derivatives were designed, synthesized
and tested for antitumor activities against six kinds of human cancer cell lines,
namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF
7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these
compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2
3, 2-16 and 3-2 was determined. The results showed: (1) among all compounds
examined, 2-16 showed the highest antitumor activity and a broader spectrum of
activity, with IC50 values ranging from 1-2 uM; (2) their solubility was
obviously improved; (3) 2-3, 2-16 and 3-2 had a significant impact inducing
apoptosis in some cancer cell lines. The preliminary structure-activity
relationships of these derivatives were discussed.
PMID- 24352028
TI - 4,6,8-Triarylquinoline-3-carbaldehyde derivatives: synthesis and photophysical
properties.
AB - Palladium catalyzed Suzuki-Miyaura cross-coupling of 6,8-dibromo-4
chloroquinoline-3-carbaldehyde with arylboronic and arylvinylboronic acid
derivatives in the presence of potassium carbonate in aqueous dioxane afforded
the corresponding 4,6,8-triarylquinoline-3-carbaldehydes, exclusively. These
products were transformed into 4,6,8-triaryl-3-(4-fluorophenyl)amino)-N-(quinolin
3-yl)methylenes and their 4,6,8-triaryl-quinoline-3-methanol derivatives. The
absorption and emission spectra were measured for the 4,6,8-triarylquinoline-3
carbaldehydes and their derivatives in selected solvents of different polarity.
PMID- 24352029
TI - Glycyrrhizin alleviates neuroinflammation and memory deficit induced by systemic
lipopolysaccharide treatment in mice.
AB - The present study investigated the effects of glycyrrhizin (GRZ) on
neuroinflammation and memory deficit in systemic lipopolysaccharide (LPS)-treated
C57BL/6 mice. Varying doses of GRZ was orally administered (10, 30, or 50 mg/kg)
once a day for 3 days before the LPS (3 mg/kg) injection. At 24 h after the LPS
injection, GRZ significantly reduced TNF-alpha and IL-1beta mRNA at doses of 30
and 50 mg/kg. COX-2 and iNOS protein expressions were significantly reduced by
GRZ at doses of 30 and 50 mg/kg. In the Morris water maze test, GRZ (30 mg/kg)
significantly prolonged the swimming time spent in the target and peri-target
zones. GRZ also significantly increased the target heading and memory score
numbers. In the hippocampal tissue, GRZ significantly reduced the up-regulated
Iba1 protein expression and the average cell size of Iba1-expressing microglia
induced by LPS. The results indicate that GRZ ameliorated the memory deficit
induced by systemic LPS treatment and the effect of GRZ was found to be mediated
through the inhibition of pro-inflammatory mediators and microglial activation in
the brain tissue. This study supports that GRZ may be a putative therapeutic drug
on neurodegenerative diseases associated with cognitive deficits and
neuroinflammation such as Alzheimer's disease.
PMID- 24352030
TI - Structural changes of the brain in relation to occupational stress.
AB - Despite mounting reports about the negative effects of chronic occupational
stress on cognitive functions, it is still uncertain whether and how this type of
stress is associated with cerebral changes. This issue was addressed in the
present MRI study, in which cortical thickness (Cth) and subcortical volumes were
compared between 40 subjects reporting symptoms of chronic occupational stress
(38 +/- 6 years) and 40 matched controls (36 +/- 6 years). The degree of
perceived stress was measured with Maslach Burnout Inventory. In stressed
subjects, there was a significant thinning of the mesial frontal cortex. When
investigating the correlation between age and Cth, the thinning effect of age was
more pronounced in the stressed group in the frontal cortex. Furthermore, their
amygdala volumes were bilaterally increased (P = 0.020 and P = 0.003), whereas
their caudate volumes were reduced (P = 0.040), and accompanied by impaired fine
motor function. The perceived stress correlated positively with the amygdala
volumes (r = 0.44, P = 0.04; r = 0.43, P = 04). Occupational stress was found to
be associated with cortical thinning as well as with selective changes of
subcortical volumes, with behavioral correlates. The findings support the
hypothesis that stress-related excitotoxicity might be an underlying mechanism,
and that the described condition is a stress related illness.
PMID- 24352031
TI - Triptolide sensitizes liver cancer cell lines to chemotherapy in vitro and in
vivo.
AB - AIM: Triptolide is a diterpenoid epoxide isolated from the herb Tripterygium
wilfordii, which has long been used as a natural medicine in China for many
diseases including cancer. However, its effect on liver cancer has not yet been
evaluated. The aim of this study is to investigate the effect of triptolide on
liver cancer cell lines. METHODS: The effect of triptolide with cancer
chemotherapeutics such as cisplatin and fluorouracil (5-FU) in vitro and in vivo
on liver cancer cells has been investigated. Cell viability and protein
expression were determined by MTT assay and Western blotting respectively.
Apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. The
antitumor effects of triptolide alone or in combination were also measured in
transplantation tumor models. RESULTS: The combination of triptolide plus
chemotherapeutics (Cisplatin, 5-FU) reduced cancer cell viability and enhanced
apoptosis compared with single treatment in vitro. Furthermore, cells treated
with triptolide plus chemotherapeutics exhibited marked production of
intracellular ROS and caspase-3 activity compared with single treatment, which
paralleled the incidence of apoptosis. Triptolide and chemotherapeutics treatment
also induced Bax expression, and inhibited Bcl-2 expression. Triptolide also
boosted the anticancerous effects of cisplatin and 5-FU in nude mice compared
with cisplatin or 5-FU alone treated tumors. CONCLUSION: Our study demonstrated
that triptolide is associated with increased cellular sensitivity of liver cancer
cells to cisplatin and 5-FU in vivo and in vitro, and may provide new liver
cancer treatment strategies.
PMID- 24352032
TI - Vacuum Rabi splitting of exciton-polariton emission in an AlN film.
AB - The vacuum Rabi splitting of exciton-polariton emission is observed in
cathodoluminescence (CL) and photoluminescence spectra of an AlN epitaxial film.
Atomic force microscopy and CL measurements show that the film has an atomically
flat surface, high purity, and high crystal quality. By changing the temperature,
anticrossing behavior between the upper and lower polariton branch can be
obtained in low temperature with a Rabi splitting of 44 meV, in agreement with
the calculation. This large energy splitting is caused by strong oscillator
strength, intrinsically pure polarization in wurtzite AlN semiconductor, and high
fraction of free exciton in the sample. These properties indicate that AlN can be
a potential semiconductor for the further development of polariton physics and
polariton-based novel devices.
PMID- 24352033
TI - Continuous adsorption in highly ordered porous matrices made by nanolithography.
AB - The exposed surface area of porous materials is usually determined by measuring
the mass of adsorbed gas as a function of vapour pressure. Here we report a
comprehensive study of adsorption in systems with closed bottom, not
interconnected pores exhibiting different degrees of disorder, produced with
methods encompassing nanolithography and dry and wet etching. Detailed adsorption
studies of these matrices show hysteresis loops, as found always in pores having
sizes of tens to hundreds of nanometres. The observed variations in the loop
shape are associated with changes in the pore morphology. In regular pores formed
by vertical and smooth walls, continuous adsorption is found for the first time
in agreement with thermodynamic considerations valid for ideal pores. This
suggests that irregularities in the walls and pore openings are the key factors
behind the hysteresis phenomenon. Interestingly, pores having rough walls but a
pyramidal shape also do not show any hysteresis.
PMID- 24352034
TI - Expansion Open-door Laminoplasty With Foraminotomy Versus Anterior Cervical
Discectomy and Fusion for Coexisting Multilevel Cervical Myelopathy and
Unilateral Radiculopathy.
AB - STUDY DESIGN: This was a clinical prospective study. OBJECTIVE: To assess whether
clinical and radiologic outcomes differ between expansion open-door laminoplasty
with foraminotomy (EOLF) and anterior cervical discectomy and fusion (ACDF) in
the treatment of coexisting multilevel cervical myelopathy and unilateral
radiculopathy (CMUR). SUMMARY OF BACKGROUND DATA: No reports to date have
compared clinical outcomes between anterior and posterior decompression for CMUR.
MATERIALS AND METHODS: We prospectively performed ACDF (n=59) in 2004, 2006, and
2008 and EOLF (n=62) in 2005, 2007, and 2009. The Japanese Orthopedic Association
(JOA) score and recovery rate were evaluated. For radiographic evaluation, the
lordotic angle and range of motion at C2-C7 were investigated. RESULTS: Only 110
patients could be followed for >3 years (EOLF/ACDF: 56/54; follow-up rate,
90.9%). Demographics were similar between the 2 groups. Compared with ACDF, in
EOLF group there were shorter operating time (144 vs. 178 min), less bleeding
(175 vs. 192 mL), and fewer complications (P<0.05). Results of JOA score and
recovery rate, at 3-year postoperative follow-up, showed no statistical
difference for the 2 groups. Cervical lordosis of ACDF increased from 13.7 to
16.2 degrees, whereas that of EOLF group decreased from 14.6 to 13.3 degrees
(P<0.05). The percentage of range of motion declined in the 2 groups (ACDF/EOLF),
57.4% versus 74.7% (P<0.05). CONCLUSIONS: The 2 surgical procedures have similar
clinical effects in treating multisegmental CMUR. However, the EOLF group
demonstrated shorter operative time, less blood loss, and fewer complications;
therefore, it proved to be a more effective and safer method.
PMID- 24352035
TI - Human dental pulp stem cells can differentiate into Schwann cells and promote and
guide neurite outgrowth in an aligned tissue-engineered collagen construct in
vitro.
AB - In the present study, we evaluated the differentiation potential of human dental
pulp stem cells (hDPSCs) toward Schwann cells, together with their functional
capacity with regard to myelination and support of neurite outgrowth in vitro.
Successful Schwann cell differentiation was confirmed at the morphological and
ultrastructural level by transmission electron microscopy. Furthermore, compared
to undifferentiated hDPSCs, immunocytochemistry and ELISA tests revealed
increased glial marker expression and neurotrophic factor secretion of
differentiated hDPSCs (d-hDPSCs), which promoted survival and neurite outgrowth
in 2-dimensional dorsal root ganglia cultures. In addition, neurites were
myelinated by d-hDPSCs in a 3-dimensional collagen type I hydrogel neural tissue
construct. This engineered construct contained aligned columns of d-hDPSCs that
supported and guided neurite outgrowth. Taken together, these findings provide
the first evidence that hDPSCs are able to undergo Schwann cell differentiation
and support neural outgrowth in vitro, proposing them to be good candidates for
cell-based therapies as treatment for peripheral nerve injury.
PMID- 24352036
TI - Cdc42 inhibits ERK-mediated collagenase-1 (MMP-1) expression in collagen
activated human keratinocytes.
AB - Following injury, keratinocytes switch gene expression programs from the one that
promotes differentiation to the one that supports migration. A common feature of
human wounds and ulcerations of any form is the expression of matrix
metalloproteinase 1 (MMP-1; collagenase-1) by leading-edge basal keratinocytes
migrating across the dermal or provisional matrix. Induction of MMP-1 occurs by
signaling from the alpha2beta1 integrin in contact with dermal fibrillar type I
collagen, and the activity of MMP-1 is required for human keratinocytes to
migrate on collagen. Thus, MMP-1 serves a critical role in the repair of damaged
human skin. Here, we evaluated the mechanisms controlling MMP-1 expression in
primary human keratinocytes from neonatal foreskin and adult female skin. Our
results demonstrate that shortly following contact with type I collagen
extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
kinase were markedly activated, whereas c-Jun N-terminal kinase (JNK)
phosphorylation remained at basal levels. ERK inhibition markedly blocked
collagen-stimulated MMP-1 expression in keratinocytes. In contrast, inhibiting
p38 or JNK pathways had no effect on MMP-1 production. Moreover, investigating
the role of Rho GTPases revealed that Cdc42 attenuates MMP-1 expression by
suppressing ERK activity. Thus, our data indicate that injured keratinocytes
induce MMP-1 expression through ERK activation, and this process is negatively
regulated by Cdc42 activity.
PMID- 24352037
TI - Periostin controls keratinocyte proliferation and differentiation by interacting
with the paracrine IL-1alpha/IL-6 loop.
AB - Proliferation and differentiation of keratinocytes are normally well balanced,
but this balance can be perturbed in wound healing and is dysregulated in
pathological conditions such as atopic dermatitis. Epithelial-mesenchymal
interaction affects this event via the cross-talk of cytokines and growth
factors. Periostin, a matricellular protein, has an important role during
reepithelialization in wound healing and is critical for hyperproliferation of
keratinocytes in atopic dermatitis. Here we investigated how periostin regulates
proliferation and differentiation of keratinocytes in the epithelial-mesenchymal
interactions using a three-dimensional organotypic air-liquid interface coculture
system. The release of IL-1alpha from keratinocytes and subsequent IL-6
production from fibroblasts were critical for keratinocyte proliferation and
differentiation. Periostin secreted from fibroblasts was required for IL-1alpha
induced IL-6 production and enhanced IL-6 production by activation of the NF
kappaB pathway synergistically with IL-1alpha. Thus, the combination of an
autocrine loop of periostin and a paracrine loop composed of IL-1alpha and IL-6
regulates keratinocyte proliferation and differentiation in the epithelial
mesenchymal interactions, and periostin tunes the magnitude of keratinocyte
proliferation and differentiation by interacting with the paracrine IL-1alpha/IL
6 loop.
PMID- 24352038
TI - Characterization of innate lymphoid cells in human skin and blood demonstrates
increase of NKp44+ ILC3 in psoriasis.
AB - Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of
tissue immunity. However, their role in human tissue homeostasis and disease
remains to be fully elucidated. Here we characterize the ILCs in human skin from
healthy individuals and from the inflammatory skin disease psoriasis. We show
that a substantial proportion of IL-17A and IL-22 producing cells in the skin and
blood of normal individuals and psoriasis patients are CD3-negative innate
lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically
significant increase in the frequency of circulating NKp44+ ILC3 in the blood of
psoriasis patients compared with healthy individuals or atopic dermatitis
patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte
associated antigen, indicating their potential for skin homing. Analysis of skin
tissue revealed a significantly increased frequency of total ILCs in the skin
compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly
increased in non-lesional psoriatic skin compared with normal skin. A detailed
time course of a psoriasis patient treated with anti-tumor necrosis factor showed
a close association between therapeutic response, decrease in inflammatory skin
lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial
observational study suggest a potential role for NKp44+ ILC3 in psoriasis
pathogenesis.
PMID- 24352039
TI - Advanced inhibition of undesired human hair growth by PPARgamma modulation?
PMID- 24352040
TI - Characterization of Spink6 in mouse skin: the conserved inhibitor of kallikrein
related peptidases is reduced by barrier injury.
AB - The proteolytic regulation of the desquamation process by kallikrein-related
peptidases (KLKs) is crucial for epidermal barrier function, and elevated KLK
levels have been reported in atopic dermatitis. KLKs are controlled by specific
inhibitors of the serine protease inhibitor of Kazal-type (Spink) family.
Recently, SPINK6 was shown to be present in human stratum corneum. In order to
investigate its role in epidermal barrier function, we studied mouse Spink6.
Sequence alignment revealed that the Kazal domain of Spink6 is highly conserved
in animals. Recombinant Spink6 efficiently inhibited mouse Klk5 and human KLK2,
KLK4, KLK5, KLK6, KLK7, KLK12, KLK13, and KLK14, whereas human KLK1 and KLK8 were
not inhibited. Spink6 was expressed in mouse epidermis mainly in the stratum
granulosum, and the inner root sheath of hair follicles. Stimulation with
flagellin, EGF, and IL-1beta did not alter Spink6 expression, whereas stimulation
with tumor necrosis factor-alpha (TNFalpha)/IFNgamma and all-trans retinoic acid
resulted in a significant downregulation of Spink6 expression in cultured primary
mouse keratinocytes. Mechanically and metabolically induced skin barrier
dysfunction resulted both in a downregulation of Spink6 expression. Our study
indicates that Spink6 is a potent inhibitor of KLKs and involved in skin barrier
function.
PMID- 24352041
TI - Analysis of pseudoxanthoma elasticum-causing missense mutants of ABCC6 in vivo;
pharmacological correction of the mislocalized proteins.
AB - Mutations in the ABCC6 gene cause soft-tissue calcification in pseudoxanthoma
elasticum (PXE) and, in some patients, generalized arterial calcification of
infancy (GACI). PXE is characterized by late onset and progressive mineralization
of elastic fibers in dermal, ocular, and cardiovascular tissues. GACI patients
present a more severe, often prenatal arterial calcification. We have tested 10
frequent disease-causing ABCC6 missense mutants for the transport activity by
using Sf9 (Spodoptera frugiperda) cells, characterized the subcellular
localization in MDCKII (Madin-Darby canine kidney (cell line)) cells and in mouse
liver, and tested the phenotypic rescue in zebrafish. We aimed at identifying
mutants with preserved transport activity but with improper plasma membrane
localization for rescue by the chemical chaperone 4-phenylbutyrate (4-PBA). Seven
of the mutants were transport-competent but mislocalized in mouse liver. The
observed divergence in cellular localization of mutants in MDCKII cells versus
mouse liver underlined the limitations of this 2D in vitro cell system. The
functionality of ABCC6 mutants was tested in zebrafish, and minimal rescue of the
morpholino-induced phenotype was found. However, 4-PBA, a drug approved for
clinical use, restored the plasma membrane localization of four ABCC6 mutants
(R1114P, S1121W, Q1347H, and R1314W), suggesting that allele-specific therapy may
be useful for selected patients with PXE and GACI.
PMID- 24352046
TI - Dual-exposure technique for extending the dynamic range of x-ray flat panel
detectors.
AB - This work presents an approach to extend the dynamic range of x-ray flat panel
detectors by combining two acquisitions of the same sample taken with two
different x-ray photon flux levels and the same beam spectral configuration. In
order to combine both datasets, the response of detector pixels was modelled in
terms of mean and variance using a linear model. The model was extended to take
into account the effect of pixel saturation. We estimated a joint probability
density function (j-pdf) of the pixel values by assuming that each dataset
follows an independent Gaussian distribution. This j-pdf was used for estimating
the final pixel value of the high-dynamic-range dataset using a maximum
likelihood method. The suitability of the pixel model for the representation of
the detector signal was assessed using experimental data from a small-animal cone
beam micro-CT scanner equipped with a flat panel detector. The potential
extension in dynamic range offered by our method was investigated for generic
flat panel detectors using analytical expressions and simulations. The
performance of the proposed dual-exposure approach in realistic imaging
environments was compared with that of a regular single-exposure technique using
experimental data from two different phantoms. Image quality was assessed in
terms of signal-to-noise ratio, contrast, and analysis of profiles drawn on the
images. The dynamic range, measured as the ratio between the exposure for
saturation and the exposure equivalent to instrumentation noise, was increased
from 76.9 to 166.7 when using our method. Dual-exposure results showed higher
contrast-to-noise ratio and contrast resolution than the single-exposure
acquisitions for the same x-ray dose. In addition, image artifacts were reduced
in the combined dataset. This technique to extend the dynamic range of the
detector without increasing the dose is particularly suited to image samples that
contain both low and high attenuation regions.
PMID- 24352045
TI - Vitamin D controls murine and human plasmacytoid dendritic cell function.
AB - Topical application of the vitamin D (VitD) analog calcipotriol is a highly
effective standard treatment modality of psoriatic skin lesions. However, the
immune modulatory effects of the treatment are incompletely understood. VitD is
well known to induce tolerogenic responses in conventional dendritic cells
(cDCs). Plasmacytoid DCs (pDCs) comprise a specialized, naturally occurring DC
subset known to be important in autoimmune diseases including psoriasis. pDCs
from the blood rapidly infiltrate psoriatic skin and are key to the initiation of
the immune-mediated pathogenesis of the disease. We now demonstrate that pDCs
express various proteins of the VitD receptor (VDR) pathway, including the VitD
metabolizing enzymes Cyp27B1 and Cyp24A1, and that VDR is transcriptionally
active in pDCs. Moreover, VitD impairs the capacity of murine and human pDCs to
induce T-cell proliferation and secretion of the T-helper 1 cytokine IFNgamma.
The inhibitory effect of VitD is dependent on the expression of the VDR in the
DCs. This study demonstrates that VitD signaling can act as a natural inhibitory
mechanism on both cDCs and pDCs, which may instigate the development of VitD
based therapeutic applications for psoriasis and other inflammatory skin
diseases.
PMID- 24352047
TI - Influence of negative stereotypes and beliefs on neuropsychological test
performance in a traumatic brain injury population.
AB - The impact of stereotype threat and self-efficacy beliefs on neuropsychological
test performance in a clinical traumatic brain injury (TBI) population was
investigated. A total of 42 individuals with mild-to-moderate TBI and 42 (age-,
gender-, educationally matched) healthy adults were recruited. The study
consisted of a 2 (Type of injury: control, TBI) * 2 (Threat Condition: reduced
threat, heightened threat) between-participants design. The purpose of the
reduced threat condition was to reduce negative stereotyped beliefs regarding
cognitive effects of TBI and to emphasize personal control over cognition. The
heightened threat condition consisted of an opposing view. Main effects included
greater anxiety, motivation, and dejection but reduced memory self-efficacy for
head-injured-groups, compared to control groups. On neuropsychological testing,
the TBI-heightened-threat-group displayed lower scores on Initial Encoding
(initial recall) and trended toward displaying lower scores on Attention (working
memory) compared to the TBI-reduced-threat-group. No effect was found for Delayed
Recall measures. Memory self-efficacy mediated the relation between threat
condition and neuropsychological performance, indicating a potential mechanism
for the threat effect. The findings highlight the impact of stereotype threat and
self-referent beliefs on neuropsychological test performance in a clinical TBI
population.
PMID- 24352044
TI - A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood
vessels.
AB - Dendritic cells (DCs), macrophages (Mphi), and T cells are major components of
the skin immune system, but their interstitial spatial organization is poorly
characterized. Using four-channel whole-mount immunofluorescence staining of the
human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood
capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs,
FXIIIa(+) Mphi, and lymphocytes. We showed phenotypic and morphological
differences in situ between DCs and Mphi. DCs formed the first dermal cellular
layer (0-20 MUm beneath the dermoepidermal junction), Mphi were located deeper
(40-60 MUm), and CD3(+) lymphocytes were observed throughout (0-60 MUm). Below
this level, DCs, T cells, and the majority of Mphi formed stable perivascular
sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes
previously underestimated from cross-section views. The total area of apical
dermis (0-30 MUm) contained approximately 10-fold more myeloid DCs than the
entire blood volume of an average individual. Surprisingly, <1% of dermal DCs
occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated
within lymphatics, but Mphi remained fixed in skin explants cultured ex vivo. The
leukocyte architecture observed in normal skin was distorted in inflammation and
disease. These studies illustrate the micro-anatomy of dermal leukocytes and
provide further insights into their functional organization.
PMID- 24352049
TI - Deferiprone, iron overload in a renal transplant patient.
PMID- 24352042
TI - Plakins, a versatile family of cytolinkers: roles in skin integrity and in human
diseases.
AB - The plakin family consists of giant proteins involved in the cross-linking and
organization of the cytoskeleton and adhesion complexes. They further modulate
several fundamental biological processes, such as cell adhesion, migration, and
polarization or signaling pathways. Inherited and acquired defects of plakins in
humans and in animal models potentially lead to dramatic manifestations in the
skin, striated muscles, and/or nervous system. These observations unequivocally
demonstrate the key role of plakins in the maintenance of tissue integrity. Here
we review the characteristics of the mammalian plakin members BPAG1 (bullous
pemphigoid antigen 1), desmoplakin, plectin, envoplakin, epiplakin, MACF1
(microtubule-actin cross-linking factor 1), and periplakin, highlighting their
role in skin homeostasis and diseases.
PMID- 24352048
TI - Large granular lymphocytosis during dasatinib therapy.
AB - Dasatinib is a second generation tyrosine kinase inhibitor (TKI) approved for
clinical use in patients with imatinib-resistant chronic myeloid leukemia (CML)
and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL).
Large granular lymphocytes (LGLs) are medium to large cells with eccentric nuclei
and abundant cytoplasm with coarse azurophilic granules. LGL lymphocytosis is
caused by a proliferation of cytotoxic (CD8+) T cells and/or NK cells. In a
proportion of CML and Ph(+) ALL patients, there is a significant expansion of
LGLs during dasatinib therapy. LGL lymphocytosis is seen in some cases with
fevers, colitis, and pleural effusions (PE), suggesting an aberrant immune
response mediated by these LGLs. LGLs may participate in the elimination of the
residual leukemic cells, and LGL clonal expansion is associated with excellent,
long-lasting therapy responses in dasatinib-treated patients. For a more
comprehensive analysis, we analyzed the morphologic, phenotypic, clinical, and
functional features of the LGL subsets amplified in vivo during dasatinib
therapy.
PMID- 24352050
TI - Air quality impacts mortality in acute medical admissions.
AB - BACKGROUND: Air quality degraded by black smoke (particulate matter, PM10),
sulphur dioxide (SO2) and nitrogen oxide (NO(x)) affects human health.
Improvements following national legislation have lowered death rates. Whether
background air pollution levels continue to affect human health remains unclear.
AIM: To determine impact of air pollutant concentrations (PM10, SO2 and NO(x)) on
in-hospital mortality for acute medical admissions to St James's Hospital over a
decade (2002-11). DESIGN: All emergency admissions (55,596 episodes in n = 32,581
patients) were tracked prospectively and mortality assessed. Daily levels of
PM10, SO2 and NO(x) were obtained from monitoring stations in our catchment area.
METHODS: Univariate and multivariate logistic regression was employed to examine
relationships between pollutant concentration and odds ratio (OR) for death
following adjustment for other mortality predictors. RESULTS: Mortality related
to each pollutant variable assessed (as quintiles of increasing atmospheric
concentration) was significantly predictive. For PM10 and SO2, mortality in the
highest three quintile concentrations (compared with base quintile) was
significantly increased (P < 0.001) with univariate ORs of 1.24, 1.36 and 1.25
for PM10 and 1.43, 1.54 and 1.58 for SO2, respectively. Mortality in all quintile
concentrations (compared with base quintile) was significantly increased (P <
0.05) for NO(x) with univariate ORs of 1.14, 1.18, 1.28 and 1.35, respectively.
Following adjustment for other mortality predictors such as acute illness
severity, all three air pollutants were independently predictive of mortality.
CONCLUSION: Despite improvement to air quality in Dublin, the prevailing
background pollutant concentrations continue to affect human health at levels
considered safe and below that previously recognized.
PMID- 24352051
TI - Manifestations of Von Hippel Lindau syndrome: a retrospective national review.
AB - INTRODUCTION: Von Hippel Lindau (VHL) disease is a syndrome that is defined by
variety of tumours such as cerebellar haemangioblastomas, renal cell carcinomas,
phaeochromocytomas, pancreatic adenomas and ear, nose and throat (ENT) adenomas.
This disease is often genetic and inherited in an autosomal dominant fashion, and
can present in childhood, adolescence or adult life. This study describes the
presentation, natural history and manifestations of patients attending our
institutions with this condition. We aim to highlight the importance of screening
in diagnosing the manifestations of VHL. METHODS: A retrospective review was
performed on all patients diagnosed with VHL and coded as such by the national
Hospital Inpatient Enquiry Scheme at Beaumont Hospital Dublin and Cork University
Hospital. This was performed over a 20 years period between 1989 and 2009. Age,
sex, mode of presentation, presence or absence of end stage kidney disease and
genotype were documented. Presence or absence of the characteristic tumours of
VHL was also recorded, as were the initial presenting features of these tumours.
RESULTS: Thirty-six patients were diagnosed with VHL. These patients ranged from
18 to 78 years old. Three patients were members of the Irish travelling
community. The most frequent mode of presentation was altered neurological signs
(40%), with a significant proportion presenting with haematuria (23%). Patients
diagnosed prior to 1995 were more likely to have presented with significant
complications of VHL, while those diagnosed after this time were more likely to
have been diagnosed via screening. Genetic testing was performed on 17 patients;
those who did not have genetic testing performed were more likely to have been
diagnosed prior to the era of genetic testing. Thirty-one patients had received
screening for complications of VHL including renal cell carcinomas, central
nervous system (CNS) haemangioblastomas and phaeochromocytomas. The patients who
did not receive any screening presented with neurological symptoms. CONCLUSION:
Beaumont Hospital Dublin and Cork University Hospital are tertiary referral
centres for nephrology, urology and neurosurgery and deals with a significant
proportion of patients diagnosed with VHL in Ireland. This study highlights the
significant burden of this illness and emphasizes the importance of screening for
these renal/CNS and ENT complications. This study also highlights the importance
of family screening in diagnosing this condition.
PMID- 24352052
TI - Adult corkscrew ureter.
PMID- 24352053
TI - Novel method of synthesis of 5''-phosphate 2'-O-ribosyl-ribonucleosides and their
3'-phosphoramidites.
AB - Synthesis of 5''-phosphate 2'-O-ribosylribonucleosides [Nr(p)] of four common
ribonucleosides, and 3'-phosphoramidites of 5''-phosphate 2'-O-ribosyladenosine
and 2'-O-ribosylguanosine using the H-phosphonate chemistry is described. An
additional ring protected by benzoyl groups was incorporated into the main
ribosyl ring in the reaction with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D
ribofuranose in the presence of SnCl4. The obtained 2'-O-ribosylribonucleosides
(Nr) were applied in the subsequent transformations with selective deprotection.
Ethanolamine was applied as a very convenient reagent for selective removal of
benzoyl groups. Additionally, the tetraisopropyldisiloxane-1,3-diyl (TIPDSi)
group was found to be stable under these deprotection conditions. Thus, the
selectively deprotected 5''-hydroxyl group of Nr was transformed into an H
phosphonate monoester which was found to be stable under the following
conditions: the removal of the TIPDSi group with triethylammonium fluoride and
the dimethoxytritylation of the 5''-hydroxyl function. The 5''-H-phosphonate of
Nr precursors was easily transformed to the corresponding dicyanoethyl 5''-O
phosphotriesters before phosphitylation, which gave 3'-phosphoramidite units of
Nr(p) in high yield. The derived phosphoramidite units were used in an automated
oligonucleotide synthesizer to produce dimer Ar(p)T via the phosphoramidite
approach. The obtained products were fully deprotected under standard
deprotection conditions giving dimers with a 5''-phosphate monoester function.
Application of an alkaline phosphatase to prove the presence of an additional
phosphate group was described.
PMID- 24352054
TI - New short strategy for the synthesis of the dibenz[b,f]oxepin scaffold.
AB - In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework
through intramolecular SNAr and McMurry reactions is described. The diaryl ethers
required for the McMurry reaction have been obtained in good yields under
microwave-assisted conditions of the reaction of salicylaldehydes with
fluorobenzaldehydes without catalysts. Application of an intramolecular McMurry
reaction to the synthesized diarylethers using TiCl4/Zn in THF gave the target
dibenzo[b,f]oxepin system in 53%-55% yields.
PMID- 24352055
TI - Characterization of flavonoids in the ethomedicine Fordiae Cauliflorae Radix and
its adulterant Millettiae Pulchrae Radix by HPLC-DAD-ESI-IT-TOF-MSn.
AB - Fordiae Cauliflorae Radix (FC, the root of Fordia cauliflora Hemsl) and
Millettiae Pulchrae Radix [MP, the root of Millettia pulchra (Benth.) Kurz var.
laxior (Dunn) Z. Wei], which go under the same local name of "Daluosan", have
long been used in Southern China for the treatment of stroke, paralysis, dementia
in children, Alzheimer's disease and other diseases. The same local name and
similar functions always confuse users. To further utilize these two ethnodrugs
and identify them unambiguously, an HPLC-DAD-ESI-IT-TOF-MSn method was developed
to separate and characterize the flavonoids in FC and MP. A total of 41
flavonoids were detected, of which six compounds were identified by comparing
their retention time and MS data with those of the reference standards, and the
others were tentatively identified based on their tandem mass spectrometry data
obtained in the positive ion detection mode. Nineteen of these characterized
compounds are reported from these two plants for the first time.
PMID- 24352056
TI - Tunable, luminescent, and self-healing hybrid hydrogels of polyoxometalates and
triblock copolymers based on electrostatic assembly.
AB - Hybrid hydrogels based on electrostatic co-assembly of polyoxometalates and ABA
triblock copolymers were readily prepared and exhibit excellent luminescence and
self-healing performance.
PMID- 24352059
TI - Nutrition and HIV infection.
AB - Nutritional status may have an impact at all stages of HIV disease. Many of the
clinical features of HIV infection cause nutritional problems and may also be
exacerbated by the presence of malnutrition. Inadequate food intake, due to a
wide variety of aetiologies, malabsorption and altered metabolism, may all
contribute to malnutrition. Additionally, factors in food, including
micronutrients, can modulate immune function. Reduced micronutrient levels are
documented at all stages of HIV infection although the significance of these
findings and how they may relate to HIV disease severity and prognosis are still
unclear. Body composition changes in adults include loss of weight with
proportionately greater loss of lean mass. Paediatric HIV infection has received
far less research attention, but growth failure is a significant nutritional
complication seen clinically. Clinical experience suggests that e 1000 arly
nutritional intervention may improve prognosis as well as quality of life.
Nutritional management in HIV disease depends on the clinical state of the
patient. Definition of the benefits of particular food factors and diets, as well
as the most appropriate nutrition support modalities, would allow rational
nutritional counselling. Better definition of the contribution food makes to
health through its social role, and the opportunities this provides in patient
care, would complement the biomedical research effort.
PMID- 24352057
TI - Designing nanotopographical density of extracellular matrix for controlled
morphology and function of human mesenchymal stem cells.
AB - Inspired by ultrastructural analysis of ex vivo human tissues as well as the
physiological importance of structural density, we fabricated nanogrooves with
1:1, 1:3, and 1:5 spacing ratio (width:spacing, width = 550 nm). In response to
the nanotopographical density, the adhesion, migration, and differentiation of
human mesenchymal stem cells (hMSCs) were sensitively controlled, but the
proliferation showed no significant difference. In particular, the osteo- or
neurogenesis of hMSCs were enhanced at the 1:3 spacing ratio rather than 1:1 or
1:5 spacing ratio, implying an existence of potentially optimized
nanotopographical density for stem cell function. Furthermore, such cellular
behaviors were positively correlated with several cell morphological indexes as
well as the expression of integrin beta1 or N-cadherin. Our findings propose that
nanotopographical density may be a key parameter for the design and manipulation
of functional scaffolds for stem cell-based tissue engineering and regenerative
medicine.
PMID- 24352061
TI - Urinary sodium and potassium in a sample of healthy adults in Sydney, Australia.
AB - Australia has had an official guideline for the last ten years, that people
should aim to consume less than 100 mmol sodium per day (equivalent to 6.0 g
NaCl). The only practical way of estimating sodium intake is from the 24-h
urinary sodium excretion. Between 1970 and 1980 average sodium excretions in
different Australian surveys ranged from 130 to 200 mmol/day (middle number 165
mmol/d). These surveys involved small numbers of subjects (n = 11 to 259) . To
see how Australians are responding to the guidelines and taking advantage of a
range of reduced salt food products now in the supermarkets, we measured urinary
sodium and potassium in 117 healthy adult subjects, mostly in the university
community. In group N (nutrition personnel) sodium excretion averaged 128 mmol/d
in females and 137 mmol/d in males. In group W (eating a western, traditional
Australian diet, no special knowledge of nutrition) urinary sodiums averaged 133
mmol/d (female) and 159 mmol/d (male). In group A (eating an Asian diet) sodiums
averaged 140 mmol/d (female) and 195 mmol/d (male). Potassium excretions were 73,
81, 72, 76, 53, and 65 mmol/day respectively in the six subgroups. We conclude
that these results possibly reflect a small downward trend in Australian sodium
intake and that sodium intake is lower in mainline Australian diets than Asian
diets. But only a minority of subjects' urinary sodiums were within the
recommended 40 to 100 mmol/d. Women excreted consistently smaller amounts of
sodium than men; the guidelines for sodium should perhaps be expressed separately
by gender. In six subjects who provided seven days' urine collections the
coefficient of variation for sodium excretion was between 20 and 35%.
PMID- 24352062
TI - Diet does not predict incidence or prevalence of non-insulin-dependent diabetes
in Nauruans.
AB - Cross-sectional and longitudinal relationships between diet and non-insulin
dependent diabetes (NIDDM) were assessed in Nauruan adults to determine if a
particular component of the diet contributed to the high prevalence of NIDDM in
this population. In 1982, 24-h dietary recall data were collected from 430
Nauruans over the age of 20, who were participating in a noncommunicable disease
(NCD) survey. In 1987 a follow-up survey was performed which included 350 of the
subjects from whom dietary data was obtained. Neither cross-sectional nor
longitudinal analyses showed any statistically significant associations between
any of the specific dietary components studied and NIDDM prevalence or incidence.
However, when nutrient intakes were adjusted for energy intake it appeared that
the age- and body-mass-index (BMI)-corrected mean intakes of total fat, total
carbohydrates, alcohol, sugar and monounsaturated fat were slightly higher in the
seven incident cases than in those who remained healthy, while intakes of
protein, fibre and cholesterol were lower. Despite the inability to demonstrate
an association between NIDDM risk and nutrient intake at the individual level,
Nauruans as a population have total energy intakes 115-135% greater than
recommended for maintenance of healthy weight, protein intakes about 250% of that
required, sugar intakes about twic 1000 e the recommended, fibre intakes only
about 30% of current recommended levels and in men a mean alcohol intake more
than three times the recommended level. This adverse diet undoubtedly contributes
to the high prevalence of obesity in the population and hence, even if there are
no direct dietary effects, to the risk of NIDDM and other diet-related diseases.
PMID- 24352060
TI - Uses of anthropometry in the elderly in the field setting with notes on screening
in developing countries.
AB - A field setting can be defined as any setting outside of a fixed, permanent, and
sophisticated health facility or research laboratory. The most important
applications of anthropometry at field level include biological anthropology,
epidemiology, clinical application, and metabolic research. Data collecting in
the field setting requires different levels of accuracy and precision; the
standardization should also consider intra- and inter-observer variability due to
the possibility of more than one observer participating in a given survey. A
field setting, in contrast to the laboratory setting, involves special conditions
that challenge the application of anthropometry. The required equipment is
different and the conditions of data collection are less rigorous. Issues
intrinsic to the target group - of education, culture and sophistication - might
be limiting factors for carrying out anthropometric surveys in field settings.
Another issue is related to interpretation of the biological, nutritional and
health significance of anthropometric findings in relationship to the elderly.
Uncertainty regarding the accuracy of chronological age, and geography and
differential survival of the elderly should be considered when designing a
survey. In addition, because the majority of the elderly now live in developing
countries, short stature should be a common finding in the age groups from these
regions. It is in these short-stature elderly populations, that there is a
problem interpreting and applying anthropometric norms or references for height
or weight derived from elderly populations of developed countries. In conclusion,
although the application of anthropometry to the field setting is feasible, given
its enormous importance to gerontological biology, nutrition and health,
researchers should consider a series of factors and paradigms when designing and
carrying out anthropometric surveys at the field level.
PMID- 24352063
TI - Nutrition and health of Victorian Aborigines (Kooris).
AB - Prior to European settlement of Australia, the health of Aboriginal people was
probably better than that of the Europeans. In the past 200 years there has been
a considerable improvement in the health of non-Aboriginal Australians, and a
deterioration in the health of Aborigines. Some improvement in Aboriginal health
has occurred in recent times. The Aboriginal people who live in Victoria are
known as Kooris. An understanding of traditional Koori diets is important because
people were generally healthy eating these diets. The traditional Koori diet was
high in dietary fibre, unrefined carbohydrates, and protein, with adequate
vitamins and minerals, and low in total fat and saturated fat, sucrose, salt, and
without alcohol. Their lifestyle also dictated a high level of physical activity
resulting in a reduced likelihood of overweight. The other notable aspect of the
traditional diet was the variety of foods consumed. The present health problems
of the Koori people stem primarily from their loss of ancestral lands, and social
and cultural disruption. Kooris went from a hunter gatherer society to one almost
entirely dependent upon mission handouts. There are many factors which may now
contribute to the continued poor health and nutrition of Kooris. The relative
importance of any of these factors is unknown. Morbidity and mortality data
provide valuable information about the overall health of populations and their
nutrition status. The Australian population is one of the healthiest in the
world. There is however a remarkable difference between the health of Aboriginal
and non-Aboriginal Australians. The leading cause of death for both male and
female Aborigines is disease of the circulatory system, including ischaemic heart
disease and stroke. Deaths due to circulatory system disease is 2.2 and 2.6 times
higher than the age adjusted Australian rates for men and women respectively, and
between 10 and 20 times higher for young and middle aged adult Aborigines. Rates
of hospital admission are 2.5-3 times higher than the rest of the population,
with the highest rates being for infants. Although mortality statistics do not
show nutrition related disorders such as obesity, non-insulin dependent diabetes
mellitus (NIDDM), and hypertension to be significant contributors to mortality,
these statistics are not representative of the problem. Across Australia the
prevalence of obesity, NIDDM, and hypertension are higher for Aborigines than the
general population. Available data on morbidity and mortality for Aborigines in
Victoria are limited, but the indication is that the overall situation is similar
to the rest of Australia. If the situation for Victoria is similar to the rest of
Australia, then this would suggest that the contemporary Koori diet is too high
in fat and perhaps alcohol, and too low in fibre and variety. Further evidence is
required to veri 644 fy this suggestion. There are several areas where
information on Koori nutrition is limited or lacking. These include food intake,
nutritional status, and dietary practices, such as cooking methods, salt and
sugar use and meal patterns. It is generally agreed that information on Koori
nutrition should be made available so that the problems can be identified, and
strategies put in place to address the problem areas.
PMID- 24352065
TI - Trends in the prevalence of excess dietary sodium intake - United States, 2003
2010.
AB - Excess sodium intake can lead to hypertension, the primary risk factor for
cardiovascular disease, which is the leading cause of U.S. deaths. Monitoring the
prevalence of excess sodium intake is essential to provide the evidence for
public health interventions and to track reductions in sodium intake, yet few
reports exist. Reducing population sodium intake is a national priority, and
monitoring the amount of sodium consumed adjusted for energy intake (sodium
density or sodium in milligrams divided by calories) has been recommended because
a higher sodium intake is generally accompanied by a higher calorie intake from
food. To describe the most recent estimates and trends in excess sodium intake,
CDC analyzed 2003-2010 data from the National Health and Nutrition Examination
Survey (NHANES) of 34,916 participants aged >=1 year. During 2007-2010, the
prevalence of excess sodium intake, defined as intake above the Institute of
Medicine tolerable upper intake levels (1,500 mg/day at ages 1-3 years; 1,900 mg
at 4-8 years; 2,200 mg at 9-13 years; and 2,300 mg at >=14 years) (3), ranged by
age group from 79.1% to 95.4%. Small declines in the prevalence of excess sodium
intake occurred during 2003-2010 in children aged 1-13 years, but not in
adolescents or adults. Mean sodium intake declined slightly among persons aged
>=1 year, whereas sodium density did not. Despite slight declines in some groups,
the majority of the U.S. population aged >=1 year consumes excess sodium.
PMID- 24352064
TI - Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility.
AB - The Tudor domain of human PHF1 recognizes trimethylated lysine 36 of histone H3
(H3K36me3). This interaction modulates the methyltransferase activity of the PRC2
complex and has a role in retention of PHF1 at DNA damage sites. We have
previously determined the structural basis for the association of Tudor with a
methylated histone peptide. Here we detail the molecular mechanism of binding of
the Tudor domain to the H3KC36me3-nucleosome core particle (H3KC36me3-NCP). Using
a combination of TROSY NMR and FRET, we show that Tudor concomitantly interacts
with H3K36me3 and DNA. Binding of the PHF1 Tudor domain to the H3KC36me3-NCP
stabilizes the nucleosome in a conformation in which the nucleosomal DNA is more
accessible to DNA-binding regulatory proteins. Our data provide a mechanistic
explanation for the consequence of reading of the active mark H3K36me3 by the
PHF1 Tudor domain.
PMID- 24352066
TI - Outbreak of staphylococcal food poisoning from a military unit lunch party -
United States, July 2012.
AB - On July 30, 2012, the emergency department at a military hospital was visited by
13 persons seeking care for gastrointestinal illness with onset 2-3 hours after a
work lunch party. The hospital responded by opening up temporary evaluation and
treatment capacity in primary-care clinics and a progressive-care unit and by
diverting one patient to a local civilian hospital. An immediate outbreak
investigation was conducted by local military public health personnel with
assistance from CDC. Initial epidemiologic analysis implicated "perlo" (a
chicken, sausage, and rice dish) and bacterial intoxication as the outbreak
mechanism. This enabled public health personnel to 1) recommend no further
consumption of perlo and 2) reassure appropriate authorities that no additional
ill persons likely would be seeking care and advise that nothing more than
supportive care of ill persons likely would be required. After interviewing party
attendees, investigators found nine additional persons who met their case
definition. Subsequent CDC laboratory analysis of a sample of perlo detected
staphylococcal enterotoxin A, supporting the epidemiologic findings. Improper
food handling and preparation measures were identified and addressed by the
appropriate authorities, who provided additional detailed education on food
preparation safety for the persons who prepared the meal.
PMID- 24352067
TI - Outbreak of Escherichia coli O104:H4 infections associated with sprout
consumption - Europe and North America, May-July 2011.
AB - In May 2011, public health authorities in Europe began investigating an outbreak
of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infections that
ultimately involved more than 4,000 persons in 16 countries. Early in the
outbreak, it became evident that international surveillance would be necessary to
determine the scope of the outbreak, characterize the disease, and identify the
source. This report describes surveillance conducted in the United States, which
involved active case-finding, use of laboratory testing protocols specific to non
O157 STEC, interviews to identify potential exposures of interest, and
documentation of clinical courses. Six cases in the United States were associated
with the outbreak. Although European epidemiologic studies, including analyses of
restaurant cohorts and traceback investigations, ultimately implicated raw
fenugreek sprouts as the food vehicle, none of the patients in the United States
definitively recalled sprout consumption. These events highlight challenges in
investigating outbreaks, particularly those caused by rare pathogens or
associated with food vehicles that are consumed in small quantities as part of
other dishes. Clinical laboratories should adhere to STEC testing recommendations
because they are critical for identification of rare or novel STEC pathogens.
Robust public health infrastructure is necessary to effectively manage and
resolve foodborne outbreaks.
PMID- 24352068
TI - Update: influenza activity - United States, September 29-December 7, 2013.
AB - CDC collects, compiles, and analyzes data on influenza activity year-round in the
United States (http://www.cdc.gov/flu/weekly/fluactivitysurv.htm). The influenza
season generally begins in the fall and continues through the winter and spring
months; however, the timing and severity of circulating influenza viruses can
vary by geographic location and season. Influenza activity in the United States
continued to increase from mid-November through the beginning of December. This
report summarizes U.S. influenza activity* during September 29-December 7, 2013.
PMID- 24352071
TI - Engineering hydrophilic conducting composites with enhanced ion mobility.
AB - Ion mobility has a direct influence on the performance of conducting polymers in
a number of applications as it dictates the operational speed of the devices. We
report here the enhanced ion mobility of poly(3,4-ethylene dioxythiophene) after
incorporation of gelatin. The gelatin-rich domains were seen to provide an ion
pathway through the composites.
PMID- 24352072
TI - Unity in action.
PMID- 24352073
TI - Who wrote that?
PMID- 24352077
TI - A new light on an old disease: adhesion signaling in pemphigus vulgaris.
AB - Disruption of desmosomal cadherin adhesion leads to the activation of
intracellular signaling pathways that are responsible for blister formation in
pemphigus vulgaris (PV). Recent studies corroborate the implication of the p38
mitogen-activated protein kinase in PV blistering via its downstream effector
mitogen-activated protein kinase activated protein kinase 2. These insights
highlight the key role of cadherins in tissue homeostasis and are expected to
change pemphigus management.
PMID- 24352078
TI - Dermatological therapy by topical application of non-pathogenic bacteria.
AB - The microbial community inhabiting skin is an important part of its defense,
acting to control immune responses and to influence susceptibility to pathogens.
In this issue, Volz et al. report that Vitreoscilla filiformis extracts modulate
mouse cutaneous inflammatory responses induces of interleukin-10 production in
dendritic cells and priming of regulatory T cells. These findings in a mouse
model of atopic dermatitis advance observations of links between bacteria and
host immunity, and they provide further evidence for novel therapeutic strategies
to treat inflammation in skin.
PMID- 24352079
TI - Hippo: hungry, hungry for melanoma invasion.
AB - The acquisition of invasive properties in melanoma is associated with a high
proclivity for metastasis, but the underlying pathways are poorly characterized.
The Hippo pathway has an important role in organ size control and is dysregulated
in some type of tumors. The present study, "Pro-invasive activity of the Hippo
pathway effectors YAP and TAZ in cutaneous melanoma" by Nallet-Staub et al.,
2013, provides the first in-depth analysis of expression of the Hippo pathway
effectors YAP (yes-associated protein) and TAZ (Tafazzin) in human melanocytic
lesions. Importantly, results from this study demonstrate a causal relationship
between YAP/TAZ levels and melanoma cell tumorigenicity and invasiveness.
PMID- 24352080
TI - The impact of MITF on melanoma development: news from bench and bedside.
AB - In the current issue, two articles highlight the impact of melanocyte
transcription factor (MITF) on melanoma development. In the first, Lister et al.
reveal in vivo proof of MITF directly regulating tumor development in BRAF(V600E)
melanomas. In the second, Sturm et al. present a clinical trial that emphasizes
the importance of the recently discovered E318K MITF germline mutation in
patients with multiple primary melanomas.
PMID- 24352081
TI - JID VisualDx Quiz: January 2014.
PMID- 24352082
TI - Transgenic mouse technology in skin biology: generation of complete or tissue
specific knockout mice.
PMID- 24352083
TI - Control-Plate Regression (CPR) Normalization for High-Throughput Screens with
Many Active Features.
AB - Systematic error is present in all high-throughput screens, lowering measurement
accuracy. Because screening occurs at the early stages of research projects,
measurement inaccuracy leads to following up inactive features and failing to
follow up active features. Current normalization methods take advantage of the
fact that most primary-screen features (e.g., compounds) within each plate are
inactive, which permits robust estimates of row and column systematic-error
effects. Screens that contain a majority of potentially active features pose a
more difficult challenge because even the most robust normalization methods will
remove at least some of the biological signal. Control plates that contain the
same feature in all wells can provide a solution to this problem by providing
well-by-well estimates of systematic error, which can then be removed from the
treatment plates. We introduce the robust control-plate regression (CPR) method,
which uses this approach. CPR's performance is compared to a high-performing
primary-screen normalization method in four experiments. These data were also
perturbed to simulate screens with large numbers of active features to further
assess CPR's performance. CPR performs almost as well as the best performing
normalization methods with primary screens and outperforms the Z-score and
equivalent methods with screens containing a large proportion of active features.
PMID- 24352084
TI - Multifunctional Co0.85Se/graphene hybrid nanosheets: controlled synthesis and
enhanced performances for the oxygen reduction reaction and decomposition of
hydrazine hydrate.
AB - Ultrathin nanosheets possess novel electronic structures and physical properties
as compared with their corresponding bulk samples. However, the controlled
synthesis of ultrathin monolayer nanosheets still remains a great challenge due
to the lack of an intrinsic driving force for anisotropic growth of two
dimensional (2D) structures. Here we demonstrate, for the first time to our
knowledge, the in situ synthesis of large-scale ultrathin single-crystalline
Co0.85Se nanosheets on graphene oxide (GO) sheets, with a thickness of 3 nm.
Owing to the synergetic chemical coupling effects between GO and Co0.85Se, the
Co0.85Se/graphene hybrid nanosheets exhibit the highest catalytic performance
among the available cobalt chalcogenide-based catalysts for the oxygen reduction
reaction (ORR). Moreover, Co0.85Se/graphene hybrid nanosheets can catalyze the
decomposition of hydrazine hydrate rapidly, with 97% of hydrazine hydrate being
degraded in 12 min and the degradation rate remaining constant over 10
consecutive cycles, thus having great potential as long-term catalysts in
wastewater treatment.
PMID- 24352085
TI - Rapid target allopurinol concentrations in the hypoxic fetus after maternal
administration during labour.
AB - OBJECTIVE: Perinatal hypoxia-induced free radical formation is an important cause
of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental
disabilities. Allopurinol reduces the formation of free radicals, which
potentially limits hypoxia-induced brain damage. We investigated placental
transfer and safety of allopurinol after maternal allopurinol treatment during
labour to evaluate its potential role as a neuroprotective agent in suspected
fetal hypoxia. DESIGN: We used data from a randomised, double-blind multicentre
trial comparing maternal allopurinol versus placebo in case of imminent fetal
hypoxia (NCT00189007). PATIENTS: We studied 58 women in labour at term, with
suspected fetal hypoxia prompting immediate delivery, in the intervention arm of
the study. SETTING: Delivery rooms of 11 Dutch hospitals. INTERVENTION: 500 mg
allopurinol, intravenously to the mother, immediately prior to delivery. MAIN
OUTCOME MEASURES: Drug disposition (maternal plasma concentrations, cord blood
concentrations) and drug safety (maternal and fetal adverse events). RESULTS:
Within 5 min after the end of maternal allopurinol infusion, target plasma
concentrations of allopurinol of >=2 mg/L were present in cord blood. Of all
analysed cord blood samples, 95% (52/55) had a target allopurinol plasma
concentration at the moment of delivery. No adverse events were observed in the
neonates. Two mothers had a red and/or painful arm during infusion. CONCLUSIONS:
A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and
provides target concentrations in 95% of the fetuses at the moment of delivery,
which makes it potentially useful as a neuroprotective agent in perinatology with
very little side effects. TRIAL REGISTRATION: The study is registered in the
Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration
system (NCT00189007).
PMID- 24352086
TI - Neuroenhancement with vitamin B12-underestimated neurological significance.
AB - Vitamin B12 is a cofactor of methionine synthase in the synthesis of methionine,
the precursor of the universal methyl donor S-Adenosylmethionine (SAMe), which is
involved in different epigenomic regulatory mechanisms and especially in brain
development. A Vitamin B12 deficiency expresses itself by a wide variety of
neurological manifestations such as paraesthesias, skin numbness, coordination
disorders and reduced nerve conduction velocity. In elderly people, a latent
Vitamin B12 deficiency can be associated with a progressive brain atrophy.
Moderately elevated concentrations of homocysteine (>10 umol/L) have been
associated with an increased risk of dementia, notably Alzheimer's disease, in
many cross-sectional and prospective studies. Raised plasma concentrations of
homocysteine is also associated with both regional and whole brain atrophy, not
only in Alzheimer's disease but also in healthy elderly people. Clinician
awareness should be raised to accurately diagnose and treat early Vitamin B12
deficiency to prevent irreversible structural brain damage.
PMID- 24352088
TI - Proceedings of the 2013 Meeting of the Australasian Section of the American Oil
Chemists Society (AAOCS).
AB - The Australasian section of the American Oil Chemists Society (AAOCS) held their
biennial meeting in Newcastle, Australia from 6 to 8 November, 2013. Over 150
scientists, researchers and industry representatives gathered for three days of
talks and discussions on a variety of lipid related topics. The AAOCS awarded its
inaugural AAOCS Award for Scientific Excellence in Lipid Research to Dr Allan
Green from the Commonwealth Scientific and Industrial Research Organisation
(CSIRO). Dr Green is deputy chief of the CSIRO Division of Plant Industry and has
been active in lipid research for several decades. His main research focus is on
plant breeding and genetic engineering techniques to develop improved oilseeds
with enhanced human nutritional value and novel industrial uses. Refer to "AAOCS
Award for Scientific Excellence in Lipid Research" for more detail of his
contributions [1].
PMID- 24352087
TI - Candidate genes involved in beneficial or adverse responses to commonly eaten
brassica vegetables in a New Zealand Crohn's disease cohort.
AB - Crohn's disease (CD) is one of the two manifestations of inflammatory bowel
disease. Particular foods are thought with CD to exacerbate their illness.
Vegetables, especially Brassicaceae, are often shunned by people with CD because
of the negative effects they are alleged to have on their symptoms. Brassicaceae
supply key nutrients which are necessary to meet recommended daily intakes. We
sought to identify the candidate genes involved in the beneficial or adverse
effects of Brassicaceae most commonly eaten, as reported by the New Zealand
adults from the "Genes and Diet in Inflammatory Bowel disease Study" based in
Auckland. An analysis of associations between the single nucleotide polymorphisms
(SNPs) and the beneficial or adverse effects of the ten most commonly eaten
Brassicaceae was carried out. A total of 37 SNPs were significantly associated
with beneficial effects (p = 0.00097 to 0.0497) and 64 SNPs were identified with
adverse effects (p = 0.0000751 to 0.049). After correcting for multiple testing,
rs7515322 (DIO1) and rs9469220 (HLA) remained significant. Our findings show that
the tolerance of some varieties of Brassicaceae may be shown by analysis of a
person's genotype.
PMID- 24352089
TI - Impact of breakfasts (with or without eggs) on body weight regulation and blood
lipids in university students over a 14-week semester.
AB - The effects of breakfast type on body weight and blood lipids were evaluated in
university freshman. Seventy-three subjects were instructed to consume a
breakfast with eggs (Egg Breakfast, EB, n = 39) or without (Non-Egg Breakfast,
NEB, n = 34), five times/week for 14 weeks. Breakfast composition, anthropometric
measurements and blood lipids were measured at multiple times. During the study,
mean weight change was 1.6 +/- 5.3 lbs (0.73 +/- 2.41 kg), but there was no
difference between groups. Both groups consumed similar calories for breakfast at
all time-points. The EB group consumed significantly more calories at breakfast
from protein, total fat and saturated fat, but significantly fewer calories from
carbohydrate at every time-point. Cholesterol consumption at breakfast in the EB
group was significantly higher than the NEB group at all time points. Breakfast
food choices (other than eggs) were similar between groups. Blood lipids were
similar between groups at all time points, indicating that the additional 400
mg/day of dietary cholesterol did not negatively impact blood lipids.
PMID- 24352090
TI - Diurnal triglyceridemia in relation to alcohol intake in men.
AB - Fasting and postprandial triglyceride concentrations largely depend on dietary
and lifestyle factors. Alcohol intake is associated with triglycerides, but the
effect of alcohol on diurnal triglyceridemia in a free living situation is
unknown. During three days, 139 men (range: 18-80 years) measured their own
capillary triglyceride (cTG) concentrations daily on six fixed time-points before
and after meals, and the total daily alcohol intake was recorded. The impact of
daily alcohol intake (none; low, <10 g/day; moderate, 10-30 g/day; high, >30
g/day) on diurnal triglyceridemia was analyzed by the incremental area under the
cTG curve (?cTG-AUC) reflecting the mean of the six different time-points.
Fasting cTG were similar between the alcohol groups, but a trend of increased cTG
was observed in men with moderate and high alcohol intake after dinner and at
bedtime (p for trend <0.001) which persisted after adjustment for age, smoking
and body mass index. The ?cTG-AUC was significantly lower in males with low
alcohol intake (3.0 +/- 1.9 mmol.h/L) (n = 27) compared to males with no (7.0 +/-
1.8 mmol.h/L) (n = 34), moderate (6.5 +/- 1.8 mmol.h/L) (n = 54) or high alcohol
intake (7.2 +/- 2.2 mmol.h/L) (n = 24), when adjusted for age, smoking and body
mass index (adjusted p value < 0.05). In males, low alcohol intake was associated
with decreased diurnal triglyceridemia, whereas moderate and high alcohol intake
was associated with increased triglycerides after dinner and at bed time.
PMID- 24352091
TI - Does vitamin D sufficiency equate to a single serum 25-hydroxyvitamin D level or
are different levels required for non-skeletal diseases?
AB - OBJECTIVE: Clarify the concept of vitamin D sufficiency, the relationship between
efficacy and vitamin D status and the role of Vitamin D supplementation in the
management of non-skeletal diseases. We outline reasons for anticipating
different serum vitamin D levels are required for different diseases. METHOD:
Review the literature for evidence of efficacy of supplementation and minimum
effective 25-hydroxyvitamin D (25-OHD) levels in non-skeletal disease. RESULTS:
Evidence of efficacy of vitamin supplementation is graded according to levels of
evidence. Minimum effective serum 25-OHD levels are lower for skeletal disease,
e.g., rickets (25 nmol/L), osteoporosis and fractures (50 nmol/L), than for
premature mortality (75 nmol/L) or non-skeletal diseases, e.g., depression (75
nmol/L), diabetes and cardiovascular disease (80 nmol/L), falls and respiratory
infections (95 nmol/L) and cancer (100 nmol/L). CONCLUSIONS: Evidence for the
efficacy of vitamin D supplementation at serum 25-OHD levels ranging from 25 to
100 nmol/L has been obtained from trials with vitamin D interventions that change
vitamin D status by increasing serum 25-OHD to a level consistent with
sufficiency for that disease. This evidence supports the hypothesis that just as
vitamin D metabolism is tissue dependent, so the serum levels of 25-OHD
signifying deficiency or sufficiency are disease dependent.
PMID- 24352092
TI - Eating disorders, physical fitness and sport performance: a systematic review.
AB - BACKGROUND: Eating disorders are health problems that are particularly prevalent
in adolescents and young adults. They are associated with considerable physical
health and psychosocial morbidity, and increased risk of mortality. We set out to
conduct a systematic review to determine their effect on physical fitness in the
general population and on sport performance in athletes. METHODS/DESIGN: A
systematic review of the relevant peer-reviewed literature was performed. For
inclusion, articles retrieved from PubMed had to be published in English between
1977 and 2013. Wherever possible, methods and reporting adhere to the guidelines
outlined in the PRISMA statement. Some additional studies were retrieved from
among those cited in the reference lists of included studies and from non
electronic databases. Literature searches, study selection, method and quality
appraisal were performed independently by two authors, and data was synthesized
using a narrative approach. RESULTS: Of the 1183 articles retrieved, twenty-nine
studies met the inclusion criteria and were consequently analysed. The available
data indicate that eating disorders have a negative effect on physical fitness
and sport performance by causing low energy availability, excessive loss of fat
and lean mass, dehydration, and electrolyte disturbance. DISCUSSION: Although the
paucity of the available data mean that findings to date should be interpreted
with caution, the information collated in this review has several practical
implications. First, eating disorders have a negative effect on both physical
fitness and sport performance. Second athletics coaches should be targeted for
education about the risk factors of eating disorders, as deterioration in sport
performance in athletes, particularly if they are underweight or show other signs
of an eating disorder, may indicate the need for medical intervention. However,
future studies are needed, especially to assess the direct effect of eating
disorders on sport performance.
PMID- 24352094
TI - The effect of carbohydrate ingestion on performance during a simulated soccer
match.
AB - AIM: This study investigated how performance was affected after soccer players,
in a postprandial state, ingested a 7% carbohydrate (CHO) solution compared to a
placebo (0% CHO) during a simulated soccer match. METHODS: Using a double-blind
placebo-controlled design, 22 trained male league soccer players (age: 24 +/- 7
years, wt: 73.4 +/- 12.0 kg, VO2max: 51.8 +/- 4.3 mL O2/kg/min) completed two
trials, separated by 7 days, during which they ingested, in random order, 700 mL
of either a 7% CHO or placebo drink during a simulated soccer match. Ratings of
perceived exertion (RPE), agility, timed and run to fatigue were measured during
the trials. RESULTS: Change in agility times was not altered by CHO vs. placebo
ingestion (0.57 +/- 1.48 vs. 0.66 +/- 1.00, p = 0.81). Timed runs to fatigue were
381 +/- 267 s vs. 294 +/- 159 s for the CHO and placebo drinks, respectively (p =
0.11). Body mass modified the relationship between time to fatigue and drink
ingestion (p = 0.02 for drink * body mass), such that lower body mass was
associated with increased time to fatigue when the players ingested CHO, but not
placebo. RPE values for the final stage of the simulated soccer match were 8.5 +/
1.7 and 8.6 +/- 1.5 for the CHO and placebo drinks respectively (p = 0.87).
CONCLUSIONS: The group data showed that the 7% CHO solution (49 g CHO) did not
significantly improve performance during a simulated soccer match in league
soccer players who had normal pre-match nutrition. However, when adjusting for
body mass, increasing CHO intake was associated with improved time to fatigue
during the simulated soccer match.
PMID- 24352093
TI - Myths, artifacts, and fatal flaws: identifying limitations and opportunities in
vitamin C research.
AB - Research progress to understand the role of vitamin C (ascorbic acid) in human
health has been slow in coming. This is predominantly the result of several
flawed approaches to study design, often lacking a full appreciation of the redox
chemistry and biology of ascorbic acid. In this review, we summarize our
knowledge surrounding the limitations of common approaches used in vitamin C
research. In human cell culture, the primary issues are the high oxygen
environment, presence of redox-active transition metal ions in culture media, and
the use of immortalized cell lines grown in the absence of supplemental ascorbic
acid. Studies in animal models are also limited due to the presence of endogenous
ascorbic acid synthesis. Despite the use of genetically altered rodent strains
lacking synthesis capacity, there are additional concerns that these models do
not adequately recapitulate the effects of vitamin C deprivation and
supplementation observed in humans. Lastly, several flaws in study design endemic
to randomized controlled trials and other human studies greatly limit their
conclusions and impact. There also is anecdotal evidence of positive and negative
health effects of vitamin C that are widely accepted but have not been
substantiated. Only with careful attention to study design and experimental
detail can we further our understanding of the possible roles of vitamin C in
promoting human health and preventing or treating disease.
PMID- 24352095
TI - Long term successful weight loss with a combination biphasic ketogenic
Mediterranean diet and Mediterranean diet maintenance protocol.
AB - Weight loss protocols can only be considered successful if they deliver
consistent results over the long term-a goal which is often elusive, so much so
that the term "yo-yo" is used to describe the perennial weight loss/weight regain
battle common in obesity. We hypothesized that a ketogenic Mediterranean diet
with phytoextracts (KEMEPHY) combined with the acknowledged health benefits of
traditional Mediterranean nutrition may favor long term weight loss. We analysed
89 male and female obese subjects, aged between 25 and 65 years who were overall
healthy apart from being overweight. The subjects followed a staged diet protocol
over a period of 12 months: 20 day of KEMEPHY; 20 days low carb-non ketogenic; 4
months Mediterranean normocaloric nutrition; a second 20 day ketogenic phase
followed by 6 months of Mediterranean normocaloric nutrition. For the majority of
subjects (88.25%) there was significant loss of weight (from 100.7 +/- 16.54 to
84.59 +/- 9.71 kg; BMI from 35.42 +/- 4.11 to 30.27 +/- 3.58) and body fat (form
43.44% +/- 6.34% to 33.63% +/- 7.6%) during both ketogenic phases followed by
successful maintenance, without weight regain, during the 6 month stabilization
phase with only 8 subjects failing to comply. There were also significant and
stable decreases in total cholesterol, LDLc, triglycerides and glucose levels
over the 12 month study period. HDLc showed small increases after the ketogenic
phases but over the full 12 months there was no significant change. No
significant changes were observed in ALT, AST, Creatinine or BUN. The combination
of a biphasic KEMEPHY diet separated by longer periods of maintenance nutrition,
based on the traditional Mediterranean diet, led to successful long term weight
loss and improvements in health risk factors in a majority of subjects;
compliance was very high which was a key determinant of the results seen.
PMID- 24352096
TI - Daily nutritional dose supplementation with antioxidant nutrients and
phytochemicals improves DNA and LDL stability: a double-blind, randomized, and
placebo-controlled trial.
AB - Reactive oxygen species are important risk factors for age-related diseases, but
they also act as signaling factors for endogenous antioxidative defense. The
hypothesis that a multi-micronutrient supplement with nutritional doses of
antioxidant nutrients and phytochemicals (MP) may provide protection against
oxidative damage and maintain the endogenous antioxidant defense capacity was
assessed in subjects with a habitually low intake of fruits and vegetables. In a
randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects
were assigned to either placebo or MP for eight weeks. Eighty subjects have
completed the protocol and included for the analysis. MP treatment was superior
at increasing serum folate (p < 0.0001) and resistance to DNA damage (p = 0.006,
tail intensity; p = 0.030, tail moment by comet assay), and LDL oxidation (p =
0.009) compared with the placebo. Moreover, the endogenous oxidative defense
capacity was not weakened after MP supplementation, as determined by the levels
of glutathione peroxidase (p = 0.442), catalase (p = 0.686), and superoxide
dismutase (p = 0.804). The serum folate level was negatively correlated with DNA
damage (r = -0.376, p = 0.001 for tail density; r = -0.329, p = 0.003 for tail
moment), but no correlation was found with LDL oxidation (r = -0.123, p = 0.275).
These results suggest that MP use in healthy subjects with habitually low dietary
fruit and vegetable intake may be beneficial in providing resistance to oxidative
damage to DNA and LDL without suppressing the endogenous defense mechanisms.
PMID- 24352097
TI - High mitochondrial accumulation of new gadolinium(III) agents within tumour
cells.
AB - The first bifunctional Gd(III) complexes covalently bound to arylphosphonium
cations and the first tumour-cell selective mitochondrial agents designed for
potential application in binary cancer therapies are reported. The highest in
vitro cellular uptake for any Gd complex reported to date is described, with
levels exceeding 10(10) Gd atoms per tumour cell.
PMID- 24352098
TI - Potential new gene therapy option with sitimagene ceradenovec for newly diagnosed
patients with glioblastoma multiforme.
AB - Glioblastoma multiforme (GBM) is associated with a poor prognosis with a 5-year
survival rate of less than 5%, making GBM one of the most aggressive neoplastic
malignancies. However significant strides have been made over the past few years
with respect to understanding the pathophysiology as well as treatment
modalities. The use of local therapies, particularly gene therapy, has been
evaluated, but have yet to make a major clinical impact on treatment of GBM. In a
study published by Westphal and colleagues in The Lancet Oncology, the use of
sitimagene ceradenovec, a first generation replication-deficient adenovirus
containing a prodrug converting enzyme, herpes-simplex virus thymidine kinase,
followed by intravenous ganciclovir administration and standard therapy was
evaluated compared with standard therapy alone. Patients who received sitimagene
ceradenovec had improved time to death or re-intervention, but did not show
improvement in overall survival. Patients receiving sitimagene ceradenovec
experienced more adverse effects related to treatment, including seizures and
hyponatremia. While further studies need to be conducted to determine clinical
significance, gene therapy appears to be a viable approach for patients who may
be resistant to chemotherapy.
PMID- 24352100
TI - Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D
biomimetic hydrogels.
AB - Cartilage loss is a leading cause of disability among adults and effective
therapy remains elusive. Neonatal chondrocytes (NChons) are an attractive
allogeneic cell source for cartilage repair, but their clinical translation has
been hindered by scarce donor availability. Here we examine the potential for
catalyzing cartilage tissue formation using a minimal number of NChons by co
culturing them with adipose-derived stem cells (ADSCs) in 3D hydrogels. Using
three different co-culture models, we demonstrated that the effects of co-culture
on cartilage tissue formation are dependent on the intercellular distance and
cell distribution in 3D. Unexpectedly, increasing ADSC ratio in mixed co-culture
led to increased synergy between NChons and ADSCs, and resulted in the formation
of large neocartilage nodules. This work raises the potential of utilizing stem
cells to catalyze tissue formation by neonatal chondrocytes via paracrine
signaling, and highlights the importance of controlling cell distribution in 3D
matrices to achieve optimal synergy.
PMID- 24352101
TI - Nutritional management of Crohn's disease with a peptide-based enteral formula.
AB - We examined a nutritional approach to the therapy of Crohn's disease with an
enteral formula ('Enterued', Terumo Corporation, Tokyo, Japan) which contains low
molecular weight peptides as a protein source. Total protein, albumin,
transferrin, prealbumin and retinol-binding protein levels were significantly
increased as indices of the nutritional status, when compared with those observed
before treatment. White blood cell count (WBC), erythrocyte sedimentation rate
and C reactive protein (CRP) as the indices of inflammation levels were reduced
significantly after the termination of the treatment, when compared with those
observed before treatment. The International Organization for the Study of
Inflammatory Bowel Disease (IOIBD) assessment scores decreased in all cases,
except for one case out of 51 cases evaluated. Deterioration in nutritional
status was not observed in any patient, but rather was maintained or improved; 42
out of the total 51 cases (82.4%) exhibited at least moderate improvement.
Treatment was discontinued on account of side effects such as abdominal
distension, abdominal pain and diarrhoea in five cases (8.1%). The enteral
formula 'Enterued', utilizing low molecular weight peptides as a nitrogen source,
appears to improve nutritional status and encourage remission of the inflammatory
process with minimal side effects.
PMID- 24352102
TI - Evaluation of a nutrition education activity for medical students in China.
AB - In China, where cancers and cardiovascular disease are the major causes of
morbidity and mortality, an important role for preventive medicine has emerged.
Therefore, preparing China's medical students to tackle contemporary health
problems requires attention to nutrition and health promotion in the medical
curriculum. To evaluate the effectiveness of a nutrition education activity for
medical students, a two-group pre-test/post-test nutrition education program was
conducted in a medical university in south-western China (n=300 per group).
Students in another south-western Chinese medical university served as controls
(n= 150 per group). Special features of the intervention were: (1) nutrition
education materials developed from (a) the results of a pre-test survey of
medical students and (b) discussions with medical students, faculty, and
physicians; and (2) a multi-channel delivery, which included a classroom lecture
discussion; a nutrition knowledge competition; a handout providing a day's
dietary allotment; campus radio and movie theatre announcements, and posters.
Analysis of variance, chi-square, and t-tests showed a significant increase
(P<0.05) in nutrition knowledge, but not in nutrition attitude score. The final
nutrition knowledge and attitude scores were also found to be related to the
students' increased exposure to the various channels (P<0.001). Also observed was
an increase in the consumption of soybean and dairy products (P<0.05). It is
concluded that the method is a useful and practical model for designing and
developing student nutrition education activities in China, as well as
demonstrating nutrition and health education methods among the medical university
community.
PMID- 24352099
TI - Sex-specific Esr2 mRNA expression in the rat hypothalamus and amygdala is altered
by neonatal bisphenol A exposure.
AB - Perinatal life is a critical window for sexually dimorphic brain organization,
and profoundly influenced by steroid hormones. Exposure to endocrine-disrupting
compounds may disrupt this process, resulting in compromised reproductive
physiology and behavior. To test the hypothesis that neonatal bisphenol A (BPA)
exposure can alter sex-specific postnatal Esr2 (Erbeta) expression in brain
regions fundamental to sociosexual behavior, we mapped Esr2 mRNA levels in the
principal nucleus of the bed nucleus of the stria terminalis (BNSTp),
paraventricular nucleus (PVN), anterior portion of the medial amygdaloid nucleus
(MeA), super optic nucleus, suprachiasmatic nucleus, and lateral habenula across
postnatal days (PNDs) 0-19. Next, rat pups of both sexes were subcutaneously
injected with 10 MUg estradiol benzoate (EB), 50 MUg/kg BPA (LBPA), or 50 mg/kg
BPA (HBPA) over the first 3 days of life and Esr2 levels were quantified in each
region of interest (ROI) on PNDs 4 and 10. EB exposure decreased Esr2 signal in
most female ROIs and in the male PVN. In the BNSTp, Esr2 expression decreased in
LBPA males and HBPA females on PND 10, thereby reversing the sex difference in
expression. In the PVN, Esr2 mRNA levels were elevated in LBPA females, also
resulting in a reversal of sexually dimorphic expression. In the MeA, BPA
decreased Esr2 expression on PND 4. Collectively, these data demonstrate that
region- and sex-specific Esr2 expression is vulnerable to neonatal BPA exposure
in regions of the developing brain critical to sociosexual behavior in rat.
PMID- 24352103
TI - Breakfast practices in the Asian region.
AB - Studies on changing dietary patterns throughout the Asian region have focused
largely on overall alterations in nutrient intakes and changes in the consumption
of various food groups. Changes in individual meal patterns have received little
attention. Although country and regional differences occur, the first meal of the
day, breakfast, tends to take the form of a traditional meal in most south-east
Asian countries. Grain and cereal products, such as rice and wheat and rice
noodles, appear to be dietary staples at breakfast In some countries, the more
traditional grain products are being replaced by alternative cereals, such as
bread. Lifestyle changes and accompanying urbanization together with rising
affluence, appear to be largely responsible for dietary alterations. The health
implications of these changes require further investigation.
PMID- 24352104
TI - Motor effects of broad beans (Vicia faba) in Parkinson's disease: single dose
studies.
AB - Broad beans (Vicia faba) are a natural source of L-dopa. To investigate a
possible role for this substance in the treatment of Parkinsonian motor
oscillations, we carried out single dose studies of Vicia faba pod mixture plus
carbidopa in six patients. Motor responses of equivalent magnitude to those of
conventional L-dopa medication occurred in five cases with mean onset of 39 min
and mean duration of 104 min. Vicia faba meals produced comparable L-dopa blood
levels to fasting standard tablet doses and recovery studies yielded 0.25% L-dopa
per weight of bean pod mixture. Vicia faba contains sufficient L-dopa to be
pharmacologically active in patients with Parkinson's disease and can potentially
be incorporated into dietary strategies to manage Parkinsonian motor
oscillations.
PMID- 24352105
TI - Principles of diet therapy in ancient Chinese medicine: 'Huang Di Nei Jing'.
AB - Huang Di Nei Jing, the first systematic Chinese medical book, was compiled from
the observations of imperial herbal doctors in the Qin and Han periods (221 BC -
220 AD). From this classic traditional source may be derived the concept of a
balanced and complete diet and probably the world's first dietary guidelines.
Basic to the tradition are han, re, wen and bu foods, respectively 'cold', 'hot',
'neutral', 'strengthening'. Basic to Chinese cuisine are jan and tsai- 'cereal'
(the rice staple and main meal) and 'dishes' to accompany the rice. Chinese
traditional medicine, as in Huang Di Nei Jing, considers the nourishment of body
and mind. It also emphasises that herbal medicine and food have the same origin.
Diet was essential to the prevention of disease which a glossary of Chinese terms
is given at the end of the paper in the Chinese tradition, was superior to
treatment.
PMID- 24352106
TI - Coronary risk in West Sumatran men.
AB - Lifestyle, food habits and blood lipid profiles were studied in two areas - one
urban and one rural of West Sumatra, Indonesia, where coconut oil is commonly
consumed. Subjects were 102 randomly selected healthy adult men aged 25 to 39
years. Variables considered were socioeconomic level, smoking habits, alcohol and
coffee consumption, food intake, indices for obesity, and blood lipid profiles.
Urban incomes were higher than in rural areas. The prevalence of cigarette
smoking was 75% in urban and 80% in rural areas. Alcohol consumption was higher
in urban (31%) than rural areas (4%). Coffee was used by 52% of urban and 38% of
rural men. However, quantities of alcohol and coffee consumed were small. Average
energy intakes were 1915 kcal (456 kJ) in the urban and 1845 kcal (439kJ) in the
rural areas. Protein intake was 55.8g (11.3% of total energy) in the urban and
46g (9.8%) in the rural areas. Fat intake was 45.0g (20.4%) in the urban and
33.5g (16%) in the rural areas. Dietary fat intake was significantly higher in
the urban compared to the rural areas (P<0.005). The average BMI (kg/m2) was 21.2
in the urban and 20.4 in the rural areas. Mean total body fat from 4 skinfolds
was 13.4 kg in the urban and 9.1 kg in the rural areas (Durnin's equation). The
waist-hip ratio was 0.90 in the urban and 0.88 in the rural areas. Concentrations
of total serum cholesterol and of LDL, the LDL-HDL cholesterol ratio and the
atherogenic index were significantly higher in the urban compared to the rural
areas (P<0.001). Serum HDL tended to increase in the urban areas. Overall, higher
economic status married men generally had the higher prevalence of coronary heart
disease risk factors.
PMID- 24352108
TI - Comparison of the International Harmonization Project, London and Gallamini
criteria in the interpretation of 18F-FDG PET/CT examinations after first-line
treatment in Hodgkin's lymphoma.
AB - OBJECTIVE: Fluorine 18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT)
has been reported to have a wide-ranging positive predictive value (PPV) in the
literary data on Hodgkin's lymphoma after first-line therapy. This study was
carried out to compare the usefulness of the International Harmonization Project,
London and Gallamini criteria in the interpretation of F-FDG PET/CT examinations
for this indication. METHODS: Data from 66 patients with a median follow-up care
of 54 months were evaluated. The initial stage had been I-II in the case of 45
patients and III-IV in the case of 21 patients. RESULTS: The analysis based on
the International Harmonization Project criteria resulted in a negative
predictive value (NPV) of 98.0% and a PPV of 62.5%. Using mediastinal blood pool
and liver activity as the thresholds for the London criteria, the NPV and PPV
were 98.0 and 62.5% and 98.1 and 71.4%, respectively. Considering only those
lesions with F-FDG uptake that was markedly higher than liver uptake as positive,
the NPV and PPV were 94.7 and 88.9%, respectively. The analysis based on the
Gallamini criteria resulted in an NPV of 96.2% and a PPV of 69.2%. CONCLUSION:
Using the London criteria with liver activity as the threshold seems to be a good
approach for the interpretation of post-treatment F-FDG PET/CT studies because of
its high accuracy and simplicity.
PMID- 24352109
TI - Catalytic covalent organic frameworks via pore surface engineering.
AB - We report a synthetic strategy for construction of the first example of
organocatalytic covalent organic frameworks via pore surface engineering. The COF
catalyst combines a number of striking features, including enhanced activity,
broad applicability, good recyclability, and high capability, to perform
catalytic transformation under continuous flow conditions.
PMID- 24352107
TI - Management of respiratory motion in PET/computed tomography: the state of the
art.
AB - Combined PET/computed tomography (CT) is of value in cancer diagnosis, follow-up,
and treatment planning. For cancers located in the thorax or abdomen, the
patient's breathing causes artifacts and errors in PET and CT images. Many
different approaches for artifact avoidance or correction have been developed;
most are based on gated acquisition and synchronization between the respiratory
signal and PET acquisition. The respiratory signal is usually produced by an
external sensor that tracks a physiological characteristic related to the
patient's breathing. Respiratory gating is a compensation technique in which time
or amplitude binning is used to exclude the motion in reconstructed PET images.
Although this technique is performed in routine clinical practice, it fails to
adequately correct for respiratory motion because each gate can mix several
tissue positions. Researchers have suggested either selecting PET events from
gated acquisitions or performing several PET acquisitions (corresponding to a
breath-hold CT position). However, the PET acquisition time must be increased if
adequate counting statistics are to be obtained in the different gates after
binning. Hence, other researchers have assessed correction techniques that take
account of all the counting statistics (without increasing the acquisition
duration) and integrate motion information before, during, or after the
reconstruction process. Here, we provide an overview of how motion is managed to
overcome respiratory motion in PET/CT images.
PMID- 24352110
TI - The skin whitening industry in the Philippines.
AB - Skin whitening is a big and booming industry in many developing countries. Its
popularity owes mainly to post-colonial, internalized racism. This study examines
whether government intervention is necessary and more efficient than market
driven approaches in addressing the health risks and harms associated with skin
whitening. We gathered empirical data on the quality and quantity of health
related information about skin whiteners with a multi-stage probability sample of
consumers in two cities in the Philippines (n=110; alpha=0.05). Regardless of
their socio-demographic characteristics, we find that cognitive biases and
information asymmetries build and sustain consumers' trust in manufacturers and
distributors of skin whiteners while, paradoxically, breeding uncertainties over
the integrity of these products. The results are product adulteration and
misbranding, leading to pricing advantages for toxic whiteners over safer
products. This has impeded regulatory efficacy. We recommend anchoring government
intervention in transaction cost-reduction, containing the externalities of skin
bleaching, and institutionalizing third party partnerships. Failure to do so
would leave consumers extremely vulnerable to the forces of supply and demand
that favor toxic whiteners, particularly in a market where voluntary collective
action is difficult to organize.
PMID- 24352112
TI - CDC guidance for evaluating health-care personnel for hepatitis B virus
protection and for administering postexposure management.
AB - This report contains CDC guidance that augments the 2011 recommendations of the
Advisory Committee on Immunization Practices (ACIP) for evaluating hepatitis B
protection among health-care personnel (HCP) and administering post-exposure
prophylaxis. Explicit guidance is provided for persons working, training, or
volunteering in health-care settings who have documented hepatitis B (HepB)
vaccination years before hire or matriculation (e.g., when HepB vaccination was
received as part of routine infant [recommended since 1991] or catch-up
adolescent [recommended since 1995] vaccination). In the United States, 2,890
cases of acute hepatitis B were reported to CDC in 2011, and an estimated 18,800
new cases of hepatitis B occurred after accounting for underreporting of cases
and asymptomatic infection. Although the rate of acute hepatitis B virus (HBV)
infections have declined approximately 89% during 1990-2011, from 8.5 to 0.9
cases per 100,000 population in the United States, the risk for occupationally
acquired HBV among HCP persists, largely from exposures to patients with chronic
HBV infection. ACIP recommends HepB vaccination for unvaccinated or incompletely
vaccinated HCP with reasonably anticipated risk for blood or body fluid exposure.
ACIP also recommends that vaccinated HCP receive postvaccination serologic
testing (antibody to hepatitis B surface antigen [anti-HBs]) 1-2 months after the
final dose of vaccine is administered (CDC. Immunization of health-care
personnel: recommendations of the Advisory Committee on Immunization Practices
[ACIP]. MMWR 2011;60 [No. RR-7]). Increasing numbers of HCP have received routine
HepB vaccination either as infants (recommended since 1991) or as catch-up
vaccination (recommended since 1995) in adolescence. HepB vaccination results in
protective anti-HBs responses among approximately 95% of healthy-term infants.
Certain institutions test vaccinated HCP by measuring anti-HBs upon hire or
matriculation, even when anti-HBs testing occurs greater than 2 months after
vaccination. This guidance can assist clinicians, occupational health and student
health providers, infection-control specialists, hospital and health-care
training program administrators, and others in selection of an approach for
assessing HBV protection for vaccinated HCP. This report emphasizes the
importance of administering HepB vaccination for all HCP, provides explicit
guidance for evaluating hepatitis B protection among previously vaccinated HCP
(particularly those who were vaccinated in infancy or adolescence), and clarifies
recommendations for postexposure management of HCP exposed to blood or body
fluids.
PMID- 24352113
TI - Food & Function news.
PMID- 24352111
TI - Forced protein unfolding leads to highly elastic and tough protein hydrogels.
AB - Protein-based hydrogels usually do not exhibit high stretchability or toughness,
significantly limiting the scope of their potential biomedical applications. Here
we report the engineering of a chemically cross-linked, highly elastic and tough
protein hydrogel using a mechanically extremely labile, de novo-designed protein
that assumes the classical ferredoxin-like fold structure. Due to the low
mechanical stability of the ferredoxin-like fold structure, swelling of hydrogels
causes a significant fraction of the folded domains to unfold. Subsequent
collapse and aggregation of unfolded ferredoxin-like domains leads to
intertwining of physically and chemically cross-linked networks, entailing
hydrogels with unusual physical and mechanical properties: a negative swelling
ratio, high stretchability and toughness. These hydrogels can withstand an
average strain of 450% before breaking and show massive energy dissipation. Upon
relaxation, refolding of the ferredoxin-like domains enables the hydrogel to
recover its massive hysteresis. This novel biomaterial may expand the scope of
hydrogel applications in tissue engineering.
PMID- 24352114
TI - Al-C hybrid nanoclustered anodes for lithium ion batteries with high electrical
capacity and cyclic stability.
AB - Structurally regulated and hybridized Al-C nanoclusters are prepared from C60 and
Al precursors by thermal evaporation-combined plasma-enhanced chemical vapour
deposition. The resulting Al-C hybrid nanoclustered anodes for Li-ion batteries
exhibit a high reversible capacity of >900 mA h g(-1) at an optimized current
density of 6 A g(-1) for over 100 cycles.
PMID- 24352115
TI - Cutaneous granulomatous eruption and successful response to potent topical
steroids in patients undergoing targeted BRAF inhibitor treatment for metastatic
melanoma.
AB - IMPORTANCE: Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an
effective, novel treatment for patients with metastatic melanoma with the V600E
BRAF mutation. This therapy is associated with squamous cell carcinomas and
keratoacanthomas. Granulomatous eruptions have not been previously reported.
OBSERVATIONS: Two patients with melanoma developed cutaneous granulomatous
eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of
treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption
concerning for progression of disease prompted cessation of treatment. After the
histopathologic diagnosis of granulomas, the patient was treated with clobetasol
ointment with resolution within days and resumption of therapy. In case 2, after
5 months of vemurafenib treatment, the patient developed a granulomatous
eruption, which resolved 3 weeks after cessation of therapy. CONCLUSIONS AND
RELEVANCE: We report 2 cases of cutaneous granulomatous eruptions on treatment
with targeted BRAF inhibitors, a previously unreported association. Although
additional investigations are necessary to better elucidate the pathogenic
mechanisms, our report includes a treatment plan that prevents unnecessary
discontinuation of therapy. Given the Food and Drug Administration approval of
vemurafenib for metastatic melanoma, clinicians should be aware of this possible
cutaneous reaction and treatment option to optimize patient management.
PMID- 24352116
TI - The aetiology of vaginal symptoms in rural Haiti.
AB - Vaginal symptoms are a common chief complaint amongst women visiting outpatient
clinics in rural Haiti. A systematic sample of 206 consecutive women over age 18
with gynaecological symptoms underwent gynaecologic examination and laboratory
testing for chlamydia, gonorrhoea, syphilis, HIV infection, trichomoniasis,
candidiasis, and bacterial vaginosis. Among 206 women, 174 (84%) presented with
vaginal discharge, 165 (80%) with vaginal itching, 123 (60%) with vaginal pain or
dysuria, and 18 (9%) with non-traumatic vaginal sores or boils. Laboratory
results were positive forChlamydia trachomatisin 5.4% (11/203), syphilis in 3.5%
(7/202), HIV in 1.0% (2/200), andNeisseria gonorrhoeaein 1.0% (2/203). Among
those that had microscopy, hyphae suggestive of candidiasis were visualized in
2.2% (1/45) and no cases of trichomoniasis were diagnosed 0% (0/45). Bacterial
vaginosis was diagnosed in 28.3% (13/46). The prevalence of chlamydia was 4.9
(95% CI: 1.3-17.7) times greater among those 25 years of age and under (10.8%)
than those older (2.3%). Chlamydia and bacterial vaginosis were the most common
sexually transmitted infection and vaginal condition, respectively, in this study
of rural Haitian adult women. The higher risk of chlamydia in younger women
suggests education and screening programmes in young women should be considered.
PMID- 24352117
TI - Population-level associations between antiretroviral therapy scale-up and all
cause mortality in South Africa.
AB - Our aim was to describe the association between increasing access to
antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009.
We undertook a longitudinal, population-level study, using antiretroviral
monitoring data reported by PEPFAR implementing partners and province-level and
national all-cause mortality records from Statistics South Africa (provider of
official South African government statistics) to analyse the association between
antiretroviral therapy and mortality. Using mixed effects models with a random
intercept for province, we estimated the contemporaneous and lagging association
between antiretroviral therapy and all-cause mortality in South Africa. We also
conducted subgroup analyses and estimated the number of deaths averted. For each
100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR
implementing partners in South African treatment programmes, there was an
associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the
following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year
after treatment reporting was seen in both adults and children, and men and
women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths
averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa
was associated with a significant reduction in national all-cause mortality.
PMID- 24352118
TI - HIV knowledge and risks among Vietnamese men who have sex with men travelling
abroad.
AB - Rapid economic and social development in Vietnam has resulted in increased
opportunities for travel and new potential routes of HIV transmission. We
conducted a cross-sectional study examining demographics, knowledge, and sexual
risk behaviour amongst 100 Vietnamese men who have sex with men who traveled
abroad in the previous 12 months. Men who have sex with men surveyed were mostly
university-educated, single, and under 30. Most travel (73%) was within Southeast
Asia and was undertaken for tourism (51%) or for work (29%). Casual sex with a
foreign partner occurred on 39% of trips. Only four were reported to have
involved in unsafe sex with a casual partner. Four reported illicit drug use.
Alcohol was widely consumed. Multivariate analysis showed that two variables,
travelling alone (OR = 5.26,p < 0.001) and a university education (OR = 4.05,p =
0.004), were significantly associated with casual sex abroad. More HIV prevention
education on the risks of sex while travelling abroad is needed for men who have
sex with men in Vietnam.
PMID- 24352119
TI - A man with oral lesions, constipation and back pain.
AB - We describe an unusual presentation of disseminated Kaposi sarcoma in a 49-year
old African-American man with AIDS who was admitted to the hospital for
constipation and back pain. Magnetic resonance imagings of the thoracic and
lumbar spine were grossly abnormal, however, a biopsy of the iliac crest was
interpreted as normal. The patient remained a diagnostic enigma until
disseminated Kaposi sarcoma was suspected, based on vascular plaque-like lesions
observed on his hard palate and right conjunctiva. Slides of the bone biopsy with
were stained for human herpes virus-8 (HHV-8) antigen, and were positive. AIDS
related skeletal manifestations of Kaposi sarcoma have been reported in the
literature but are infrequent.
PMID- 24352120
TI - Alarming epidemics of human immunodeficiency virus and hepatitis C virus among
injection drug users in the northwestern bordering state of Punjab, India:
prevalence and correlates.
AB - In this study 1155 injection drug users (IDUs) receiving targeted intervention in
five cities of Punjab were surveyed; three cities (Amritsar, Taran-Taran, Batala)
were in districts sharing an international border with Pakistan and the other two
were Jalandhar and Ludhiana. Information on socio-demography, substance use and
sexual practices were collected; blood samples were tested for biologic markers.
HIV and HCV antibody (HCVAb) prevalences in injection drug users were 29 and 49%,
respectively. Of the HCVAb-seroreactive IDUs, 33% had HIV as well. HIV prevalence
in young IDUs (<=19 years), estimated as surrogate for HIV incidence, was high at
12% and HCVAb in this subgroup was 27%. Herpes simplex virus 2 antibody (IgG) was
detected in 10% of IDUs; 2% had syphilis. Alcohol use prevalence was high and
frequency of use concerning. In multivariate analyses, 'city of residence closer
to international border' and '>1 year duration of injecting drugs were associated
with HIV and HCVAb. Furthermore, 'irregular supply of syringes and needles' was
associated with HCVAb seroreactive status of IDUs (adjusted odds ratio 1.7; 95%
CI 1.3-2.3;P < 0.001), and 'any genital disease symptom within the last year'
(adjusted odds ratio 2; 95% CI 1.4-2.9;P < 0.001) was associated with HIV
infection. Alcohol and sexual risk reduction, strengthening of needle-syringe
exchange, reducing injecting duration and clinical management of HIV, HCV and
HIV/HCV co-infection appear as four core programme needs.
PMID- 24352121
TI - Dietary intake and nutritional status of HIV-1-infected children and adolescents
in Florianopolis, Brazil.
AB - This cross-sectional study aimed to investigate the nutritional status and
dietary intake of HIV-infected children and adolescents and the relationship
between nutritional status and dietary intake and CD4(+) T-cell count and viral
load. The sample was composed of 49 subjects aged 7-17 years and living in
Florianopolis, Brazil. Nutritional status was assessed by height-for-age and body
mass index-for-age. Dietary intake was assessed by a food frequency
questionnaire. Spearman correlations and multiple linear regressions were used to
determine the relationship between energy, nutrient intake and body mass index
for-age and CD4(+) T-cell count and viral load. The mean body mass index-for-age
and height-for-age values were -0.26 +/- 0.86 and -0.56 +/- 0.92, respectively.
The energy intake was 50.8% above the estimated energy requirement and inadequate
intake of polyunsaturated fat, cholesterol, fibre, calcium and vitamin C was
present in 100%, 57.1%, 40.8%, 61.2% and 26.5% of the sample, respectively.
Multiple linear regression analyses revealed that energy intake was correlated
with CD4+ T-cell count (r = 0.33; p = 0.028) and viral load (r = -0.35; p =
0.019). These data showed low body mass index-for-age and height-for-age z
scores, high energy intake and inadequate intake of important nutrients for
immune function, growth and control of chronic diseases. A lower energy intake
was correlated with viral suppression and immune preservation.
PMID- 24352122
TI - Systematic review of cognitive behavioural interventions for HIV risk reduction
in substance-using men who have sex with men.
AB - Men who have sex with men (MSM) experience disproportionately high rates of HIV
and substance use. Though interventions based on cognitive behavioural therapy
(CBT) are effective for many psychiatric disorders, systematic reviews of CBT for
substance use present mixed results and CBT has not been systematically reviewed
for HIV risk reduction in MSM. Randomised controlled trials (RCTs) of non
pharmacological CBT for substance-using MSM were systematically reviewed to
assess the evidence for these interventions' impact on unprotected anal
intercourse (UAI). We searched 20 databases on 22 September 2012. Of the 2801
records identified, both authors separately assessed 70 full-text articles for
inclusion. In three included RCTs, one RCT compared CBT against non-treatment
control and two RCTs compared CBT against CBT variants. Across studies, CBT led
to UAI reductions, though at one-year follow-up, these reductions were generally
not greater than in other trial arms. This evidence of moderate quality indicates
that while CBT may reduce UAI in substance-using MSM, it is unclear if CBT is
more effective than mere assessment. All RCTs tested intensive, clinic-based
interventions requiring sustained participant commitment, indicating a need for
research into briefer interventions, with particular focus on episodic substance
use and effectiveness trials.
PMID- 24352123
TI - Prevalence of vitamin D deficiency in HIV-positive, antiretroviral treatment
naive patients in a single centre study.
AB - The objective of this study was to describe the prevalence of vitamin D
deficiency among antiretroviral treatment-naive, HIV-positive individuals. We
reviewed records of consecutive antiretroviral treatment-naive patients,
registering for care for the first time at a London clinic from 01 January 2008
to 31 December 2009. During this period, serum 25-hydroxycholecalciferol was
measured routinely for all new patients. 25-hydroxycholecalciferol deficiency and
severe deficiency were defined as <=50 and <=25 nmol/L, respectively. Among 253
patients (82% men, median age 36 years, 64% white ethnicity), 148 (58.5%) were 25
hydroxycholecalciferol-deficient, including 32 (12.6%) who were severely
deficient. In all, 73.5% (61/83) patients of non-white ethnicity were 25
hydroxycholecalciferol-deficient compared with 50.7% (76/150) of those reporting
white ethnicity (p < 0.001). Seven of eight (87.5%) patients with hypocalcaemia
(<2.12 nmol/L) were 25-hydroxycholecalciferol-deficient. The prevalence of 25
hydroxycholecalciferol-deficiency was higher in winter and spring vs. summer and
autumn (89/129 [69.0%] vs. 59/124 [47.6%],p < 0.001). Serum 25
hydroxycholecalciferol deficiency was not associated with gender, CD4 count, HIV
viral load or clinical stage. Serum 25-hydroxycholecalciferol deficiency was
common among antiretroviral treatment-naive patients, with those of non-white
ethnicity at highest risk. CD4 count, HIV viral load and HIV clinical staging do
not help to identify those at risk, but low serum calcium should prompt
investigation of 25-hydroxycholecalciferol levels.
PMID- 24352124
TI - Limited spread of hepatitis C among HIV-negative men who have sex with men in
Stockholm, Sweden.
AB - Reported cases of hepatitis C (HCV) have been increasing among HIV-positive men
who have sex with men (MSM) in many cities worldwide, including Stockholm,
Sweden. This study was performed in order to see whether there is also an
increase of HCV among HIV-negative MSM. A total number of 1008 MSM attending a
clinic for sexually transmitted infections (STI) were screened for HCV. A
confirmed positive HCV antibody screening test was found in five cases. Two of
these also tested positive for HCV-RNA. We conclude that there is limited spread
of HCV among MSM in Stockholm, and the prevalence of HCV among HIV-negative MSM
is similar to that found in the general population.
PMID- 24352125
TI - A case of multicentric Castleman's disease in HIV infection with the rare
complication of acquired angioedema.
AB - Multicentric Castleman's disease (MCD), a polyclonal lymphoproliferative disorder
of unknown aetiology, is a well-recognised complication of HIV disease. We
present a case of MCD in an HIV-positive patient that is unusual on two counts:
our patient's MCD first presented in the context of an immune restoration
inflammatory syndrome (IRIS), following the initiation of highly active
antiretroviral therapy (HAART). In addition, her MCD was associated with the
unusual complication of acquired angioedema (AAE), which resolved following
treatment of the MCD. While AAE is frequently found to have an underlying
diagnosis of a lymphoproliferative disease, this is the first reported case
linking AAE to MCD.
PMID- 24352126
TI - Direct monthly highly active antiretroviral therapy supply - a method to increase
patient's adherence and outcome. Experience of one AIDS centre in Israel.
AB - In Israel, antiretroviral therapy (ART) is available (at local pharmacies)
without cost. Nevertheless, poor adherence, especially of immigrants from Africa,
leads to a high rate of treatment failures. Our study looked whether direct
monthly ART supply in our AIDS centre has an effect on adherence and outcome. A
total of 385 HIV (clade C) immigrants from Africa that were treated with ART for
>2 years prior to the initiation of the study were evaluated. During the first 2
years, ART medications were supplied by local pharmacies. Thereafter (next 2
years), all patients received medications, monthly at our centre. Adherence,
immunological (CD4) and virological (VL) outcome at the end of the two study
periods were determined. At baseline, only 75% of the patients attended more than
90% of scheduled visits with 57% treatment adherence. Virological failure (VL >40
copies/ml) was observed in 53% of the patients. As a result of our intervention
(2 years of direct monthly ART supply), visits and treatment adherence
significantly increased (90% and 84%, respectively;p < 0.001). Concomitantly,
virological failure rate significantly dropped to 28% (p < 0.001). Direct monthly
supply of ART is a relatively low-cost mode to improve patient's adherence and
immunological/virological outcomes.
PMID- 24352127
TI - Large-scale HIV testing in the older population in China: findings from a cross
sectional study.
AB - Aiming to explore universal HIV testing, and to understand the exact HIV
prevalence in the older general population, we conducted a community-based cross
sectional epidemiological investigation in two counties of Zhejiang province,
China. Using census strategy and convenience sampling method, those participants
who were older than 50 years and met eligibility criteria were enrolled, and HIV
prevalence was presented as a crude infection rate. A total of 215,441 (64.82%)
were enrolled into this study, HIV testing was added into their health exam plan
and 18 were confirmed as HIV positive, giving a crude rate of 0.84/10,000. HIV
prevalence was higher among men than among women in all age groups (p < 0.05).
Unlike previous research, 14 cases (78%) still had a relatively high CD4 + count;
17 cases (94%) had been infected by sexual transmission. Active large-scale HIV
screening by integrating into routine health care can be an effective strategy to
find people living with HIV at relative early stage of disease.
PMID- 24352128
TI - Epidemiology of syphilis infection among drug users at methadone maintenance
treatment clinics in China: systematic review and meta-analysis.
AB - Illicit drug trade has re-emerged in China since 1979 and the number of drug
addicts had increased. Syphilis is mainly spread through sexual contact and
blood. The incidence of syphilis is high among drug users. Methadone maintenance
treatment (MMT) clinics have been implemented in China since 2004. The aim of
this study was to estimate the prevalence and risk factors of syphilis among drug
users at MMT clinics in China between 2004 and 2013. Chinese and English
databases (CBM, CNKI, Weipu, Pubmed) of literature were searched for studies
reporting syphilis among drug users in MMT clinics from 2004 to 2013. The
prevalence estimates and risk factors were summarized through a systematic review
and meta-analysis of published literatures. In all, 29 eligible articles with a
total of 8899 drug users, were selected in this review. The pooled prevalence of
syphilis infection was 7.78% (95%CI: 5.83%-9.99%). The meta-analyses demonstrated
significant differences in syphilis infection rates between men and women (OR =
0.34 [95%CI: 0.26-0.45]) but not between drug users and non-intravenous drug
users (OR = 0.82 [95%CI: 0.51-1.32]). Enhanced detection of syphilis and health
promotion is warranted in MMT clinics in China.
PMID- 24352129
TI - 2013 European Guideline on the management of proctitis, proctocolitis and
enteritis caused by sexually transmissible pathogens.
AB - Proctitis is defined as an inflammatory syndrome of the distal 10-12 cm of the
anal canal, also called the rectum. Infectious proctitis can be sexually
transmitted via genital-anal mucosal contact, but some also via mutual
masturbation.N. gonorrhoeae,C. trachomatis(including lymphogranuloma venereum),
Herpes Simplex Virus andT. pallidumare the most common sexually transmitted
anorectal pathogens. Shigellosis can be transferred via oral-anal contact and may
lead to proctocolitis or enteritis. Although most studies on these infections
have concentrated on men who have sex with men (MSM), a significant proportion of
women have anal intercourse and therefore may also be at risk. A presumptive
clinical diagnosis of proctitis can be made when there are symptoms and signs,
and a definitive diagnosis when the results of laboratory tests are available.
The symptoms of proctitis include anorectal itching, pain, cramps (tenesmus) and
discharge in and around the anal canal. Asymptomatic proctitis occurs frequently
and can only be detected by laboratory tests. The majority of rectal chlamydia
and gonococcal infections are asymptomatic. Therefore when there is a history of
receptive anal contact, exclusion of anorectal infections is generally indicated
as part of standard screening for sexually transmitted infections (STIs). Condom
use does not guarantee protection from bacterial and protozoan STIs, which are
often spread without penile penetration.
PMID- 24352130
TI - Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive
drug users receiving antiretroviral therapy in Hanoi, Vietnam.
AB - The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among
injection drug users and commercial sex workers. Socio-demographics, substance
use and clinical correlates of antiretroviral therapy non-adherence were studied
in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6
months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9
+/- 4.9 years. The median duration on antiretroviral therapy was 16.2 +/- 12.7
months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a
subjective one-item Likert scale at time of study enrollment; 48% of participants
reported drug use within the previous 6 months, with 22% reporting current drug
use. Injection drug use with or without non-injection drug use in the past 6
months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I.
1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings
support Vietnam's ongoing scale-up of harm reduction programmes for injection
drug users and their integration with antiretroviral therapy delivery. Moreover,
results highlight the need to identify and implement new ways to support high
levels of antiretroviral therapy adherence as duration on antiretroviral therapy
increases.
PMID- 24352131
TI - HIV prevalence and risk in long-distance truck drivers in South Africa: a
national cross-sectional survey.
AB - We estimated the prevalence of HIV and assessed correlates of HIV infection in
long-distance truck drivers in South Africa. Between October 2003 and July 2004,
1900 long-distance truck drivers aged >=18 years consented to interview and for
testing for HIV. Participants were selected from a 10% stratified random sample
of registered truck depots. A proximate-determinants framework was used to assess
the hierarchical relationship between risk factors and HIV infection using
logistic regression. HIV prevalence was 26% (95% confidence interval 24% to 28%).
In multivariate analyses, HIV infection was associated with spending 2-4 weeks on
the road (adjusted odds ratio 1.4; 95% confidence interval 1.1 to 1.9). There was
modest evidence of a dose-response relationship between time on the road and HIV
risk. Mobility increased risk by creating conditions for unsafe sex and reducing
access to health services. Targeted HIV interventions for long-distance truck
drivers are needed.
PMID- 24352132
TI - Psychosocial correlates of HIV testing among men who have sex with men in Italy:
a cross-sectional study.
AB - The objective of this study was to understand the psychosocial correlates of men
having sex with men (MSM) who have never been tested (never testers), MSM who
have been tested in the last 12 months (recent testers), and MSM who have been
tested before (remote testers). A sample of 14,409 Italian HIV-negative adult MSM
was recruited via instant messages to the members of five international
commercial websites and through clickable banner advertisements on different
websites. The most important correlates of never testers compared to recent
testers were younger age, sexual orientation concealment, unawareness of free HIV
services, having had a partner of unknown serostatus, and lower levels of HIV
testing self-efficacy (i.e. the belief in one's own ability to get a test for
HIV). The most important correlates of remote testers compared to recent testers
were older age, homosexual orientation, having had a partner of unknown
serostatus, unawareness of free HIV services, and lower level of HIV testing self
efficacy. There are different psychosocial correlates of MSM based on HIV testing
history. Based on the findings of this study, prevention efforts should be
directed toward increasing awareness about the availability of HIV testing
services and HIV testing self-efficacy among MSM.
PMID- 24352133
TI - Clinical and epidemiological characteristics of individuals with very high rapid
plasma reagin.
AB - The objective of the study was to identify clinical and epidemiological
characteristics of patients with infectious syphilis who presented with a high
rapid plasma reagin (RPR) titre (>=1: 512) during the year of 2009 at the Miami
Dade County Health Department (MDCHD) STD clinic. Potential cases were identified
by a search in the electronic database. Among 519 individuals identified with
reactive RPR, 190 individuals met criteria for infectious syphilis and 32 of them
had at least one RPR titre of >=1: 512. We found that the majority of individuals
with high RPR were men who have sex with men (82%), from ethnic minorities (91%),
and HIV infected (75%) but only 3 of them were on antiretroviral therapy.
Overall, 50% of these patients with very high RPR titres were symptomatic, and
the most common symptom was skin rash (93%).
PMID- 24352134
TI - Rectal Chlamydia in heterosexual women: more questions than answers.
AB - The aim of this study was to observe the proportion of concurrent rectal
Chlamydia (RCt) infection in women who have cervical Chlamydia (CCt) and to
observe whether there was any correlation with receptive anal intercourse (RAI).
Untreated CCt-positive women were invited to take part. Women chose either to
have a physician-collected or self-taken rectal swab. Treatment was then
commenced. 17 samples were physician-collected and 80 were self-collected. 75/97
(77.3%, 95% Confidence Interval [95%CI] 69.0-85.7%) were RCt positive. 25/97
(25.8%, 95%CI 17.1-34.5%) reported RAI. There was no difference in the positivity
rate whether RAI was reported (80%) or not (76%) (P = 0.71); or whether swabs
were physician-collected (65%) or self-taken (80%) (P = 0.17). Only one of those
with RCt reported rectal symptoms. One woman had concurrent gonococcal infection.
34/97 (35%) had a history of past sexually transmitted infections. Verified
contact attendance was 0.52 and 72% of verified contacts were Chlamydia positive.
Reported RAI may not be helpful in guiding RCt testing. RCt infection in women
may be more prevalent than previously thought. We do not know whether RCt
infections are clinically significant or whether they may act as a reservoir for
re-infection. RCt infections in women require further study.
PMID- 24352135
TI - Exploration of gender differences of Chlamydia trachomatis infection amongst
young people reveals limitations of using sexual histories to assess risk in high
prevalence areas.
AB - In England, chlamydia positivity in young men occurs at a slightly older age
group (20-24 years) than positivity among young women (16-20 years) but total
rates of infection among the population aged under 25 years are similar. Where
there is variation, explanations often focus on individual sexual risk
behaviours. We aimed to explore the extent to which variations in chlamydia
positivity could be explained by reasons for attendance and sexual behaviour at a
sexual health clinic in a high-prevalence area of England. Data routinely
collected during clinic appointments were extracted retrospectively from the
medical records of 952 clinic users (634 women) aged 16 to 24. We tested for
associations with chlamydia positivity using the Chi square statistic and
multiple logistic regression for men and women separately; 19.5% of men tested
positive (95% CI: 15.1-23.8) compared to 11.5% of women (95% CI: 9.0-14.0).
Reporting a partner with symptoms or a sexually transmitted infection diagnosis
was significantly associated with a positive diagnosis (Men OR: 3.14, 95% CI: 1.5
6.25; Women OR: 3.78, 95% CI: 1.83-7.83). All other reasons for attendance and
all sexual behaviour variables were not significantly associated with a positive
diagnosis. Differences in chlamydia positivity between men and women attending
this service cannot be explained by individual sexual behaviours found to be
associated with higher risk of infection in national studies. Our findings
question the utility of individual behavioural data routinely collected during
clinic appointments for predicting risk of sexually transmitted infections in
high-prevalence areas.
PMID- 24352137
TI - Activation of gaseous PH3 with low coordinate diaryltetrylene compounds.
AB - The reaction of phosphine gas with a low coordinate diaryl germylene or
diarylstannylene results in both oxidative addition and arene elimination at the
group 14 atom. The products were characterised by (31)P NMR spectroscopy and X
ray crystallography, and represent the first P-H bond activation by a heavy group
14 element compound.
PMID- 24352136
TI - A patient with HIV and tuberculosis with diminished clopidogrel response.
AB - Patients with HIV are at an increased risk for cardiovascular disease, both as a
result of treatment with protease inhibitors and from the disease itself. The
medication regimens of patients with HIV and cardiovascular comorbidities are
complex and require careful assessment for potentially serious drug-drug
interactions. We report a case of clopidogrel non-responsiveness in a patient
with HIV, latent tuberculosis and cardiovascular disease with a history of
myocardial infarction. To our knowledge, this is the first report of significant
drug interactions between clopidogrel, isoniazid and ritonavir. This case
underscores the importance of a detailed drug interaction screening in infectious
disease patients taking complex medication regimens, including clopidogrel.
PMID- 24352138
TI - Controllable fabrication of oriented micro/nanowire arrays of dibenzo
tetrathiafulvalene by a multiple drop-casting method.
AB - A multiple drop-casting method of growing the ultralong dibenzo
tetrathiafulvalene (DB-TTF) micro/nanowire arrays has been developed which has
the success ratio as high as 94%. This method enables the arrays with a length
over a few hundreds of micrometers to locate between droplets with the definite
orientation. The width of the micro/nanowires is controlled via tuning the
concentration of DB-TTF solution in dichloromethane. The large-scale arrays can
be grown onto Si, SiO2, glass, and the flexible polyethylene terephthalate (PET)
substrates. These results show the promising potential of this facile solution
based process for the growth of the high-quality organic micro/nanowires, the
fabrication of high-performance and flexible devices, and the fabrication of
controlled assemblies of nanoscale circuits for fundamental studies and future
applications.
PMID- 24352139
TI - Spatial optimization of carbon-stocking projects across Africa integrating
stocking potential with co-benefits and feasibility.
AB - Carbon offset projects through forestation are employed within the emissions
trading framework to store carbon. Yet, information about the potential of
landscapes to stock carbon, essential to the design of offset projects, is often
lacking. Here, based on data on vegetation carbon, climate and soil, we quantify
the potential for carbon storage in woody vegetation across tropical Africa. The
ability of offset projects to produce co-benefits for ecosystems and people is
then quantified. When co-benefits such as biodiversity conservation are
considered, the top-ranked sites are sometimes different to sites selected purely
for their carbon-stocking potential, although they still possess up to 92% of the
latter carbon-stocking potential. This work provides the first continental-scale
assessment of which areas may provide the greatest direct and indirect benefits
from carbon storage reforestation projects at the smallest costs and risks,
providing crucial information for prioritization of investments in carbon storage
projects.
PMID- 24352140
TI - Glycaemic index of some commonly consumed foods in western India.
AB - Glycaemic index (GI) was determined in 36 non-insulin-dependent diabetes mellitus
(NIDDM) patients. The subjects were fed 50g carbohydrate portions of six foods
consumed widely in India including Varagu (Plaspalum scorbiculatum) alone and in
combination with whole and dehusked greengram (Phaseolus aureus Roxb), Bajra
(Penniseteum typhoideum), Jowar (Sorghum vulgare) and Ragi (Eleusine coracana).
The GI of Varagu alone, Varagu in combination with whole greengram and Bajra was
significantly lower than that of Ragi which produced a glycaemic response
equivalent to that of the glucose load.
PMID- 24352141
TI - Iodine content in drinking water not an important determinant of endemic goitre.
AB - The prevalence of goitre was determined in several communities in rural parts of
Pahang. Urine specimens were collected randomly among the participants. Drinking
water from various sources such as river and spring, and water from gravity feed
systems was also collected to determine the iodine content by using the ashing
method. The results were compared to that of Kuala Lumpur City. lt was found that
the prevalence of goitre in rural areas was between 20 and 70% depending on
village, ethnic group, age and gender. The interior parts of the jungle where
Aborigines lived was moderately endemic with goitre prevalence of goitre more
than 20% and urinary iodine content 2.0-5.0 MUg I/dl). A nearby Malay traditional
village which was studied had mild endemia (prevalence 10-30% and urinary iodine
content 5.0-10.0 MUg I/dl) while a Felda Malay resettlement scheme and Kuala
Lumpur City did not have endemic goitre. Endemic goitre in rural areas was
associated with low iodine content in drinking water. Even though Kuala Lumpur
had low iodine content in its drinking water there was no endemic goitre,
indicating that other factors were more important.
PMID- 24352142
TI - Iodine status in pregnancy.
AB - The iodine status of 429 pregnant women in different trimesters from the lower
socio-economic strata of the urban slums of Bombay was assessed using clinical
and biochemical parameters. The total goitre rate (TGR) of 45% and a visible
goitre rate (VGR) of 3.04% was observed. There was an evident increase in the TGR
during the months of pregnancy. The urinary iodine excretion pattern revealed
mild iodine deficiency. 55% of the women had urinary iodine excretion less than 5
mcg/dl with 13.2% having less than 2 mcg/dl. Elevated T3 and T4 levels were
observed in 64 and 40% respectively of the women surveyed, while only 1.8% of
them had TSH levels higher than the normal range. No significant difference in
the levels of thyroid hormone (T3 or T4) was noted between the euthyroid and
goitrous subjects. The mean TSH levels in euthyroid women were however
significantly higher than those with signs of goitre.
PMID- 24352143
TI - Effects of seasonality on blood ionized calcium in early neonatal periods.
AB - The levels of whole blood ionized calcium were observed in 200 healthy neonates
in the first week of life in spring and in summer. Levels of blood ionized
calcium were lower in neonates born in spring compared to those of neonates born
in summer. The levels of blood ionized calcium in adults did not change in
different seasons. This study suggested that seasonality had a significant effect
on blood ionized calcium in early neonatal life.
PMID- 24352144
TI - Long-term tocotrienol supplementation and glutathione-dependent enzymes during
hepatocarcinogenesis in the rat.
AB - The effects of long-term administration of tocotrienol on hepatocarcinogenesis in
rats induced by diethyl nitrosamine (DEN) and 2-acetylaminofluorene (AAF) were
investigated by the determination of plasma and liver gamma-glutamyl
transpeptidase (GGT), cytosolic glutathione reductase (GSSG-Rx), glutathione
peroxidase (GSH-Px) and glutathione S-transferase (GST). Twenty-eight male Rattus
norwegicus rats (120-160g) were divided according to treatments into four groups:
control group, tocotrienol - supplemented diet group (30mg/kg food), DEN/AAF
treated group and DEN/AAF treated plus tocotrienol-supplemented-diet group
(30mg/kg food). The rats were sacrificed after nine months. The results obtained
indicated no difference in the morphology and histology of the livers of control
and tocotrienol-treated rats. Greyish-white neoplastic nodules (two per liver)
were found in all the DEN/ AAF treated rats (n-10) whereas only one nodule was
found in one of the carcinogen treated rats receiving tocotrienol supplementation
(n-6). Histological examination showed obvious cellular damage for both the
DEN/AAF-treated rats and the tocotrienol-supplemented rats but were less severe
in the latter. Treatment with DEN/AAF caused increases in GGT, GSH-Px, GST and
GSSG-Rx activities when compared to controls. These increases were also observed
when tocotrienol was supplemented with DEN/AAF but the increases were less when
compared to the rats receiving DEN/AAF only.
PMID- 24352145
TI - Nutritional factors in carcinogenesis.
AB - There have been varying estimates of the role of nutritional as opposed to other
contributors to carcinogenesis. Several considerations probably account for the
different estimates: (1) genetic overestimates because of foetal and early life
rearing practices and the nutritional modulation of genetic expression (2) errors
in food intake methodology (3) the limitations of nutrient carcinogenesis
hypotheses, ie models which are too naive and do not allow for non-nutrients in
food, food patterns and the overall package which is food culture (4) indirect
pathways connecting nutrition and cancer such as that via immunosurveillance.
Examples of cancers where rapid change in nutritional thinking is underway are
breast, prostatic, colorectal and pancreatic. With breast cancer, weakly
oestrogenic compounds from foods may be comparable to tamoxifen. Changing food
culture away from that rich in phyto-oestrogens may increase the risk of
prostatic cancer in men as well. Colorectal cancer incidence has continued at
high rates in urbanized society despite an awareness of dietary contribution
comparable to the knowledge of diet and coronary heart disease is the analysis
sufficiently stratified for large bowel site or nutritionally sophisticated
enough to allow for aggregate food pattern effects? Pancreatic cancer on the rise
presents questions about unidentified changes continuing in the diets of
industrialized societies, possibly from an early age, and even during infant
feeding. Nutritional surveillance with mathematical modelling of food intake at a
more sophisticated level will be required to understand present food-cancer
relationships, and those which may emerge with newer food technologies,
especially those related to designer foods.
PMID- 24352148
TI - Molecular insights provide the critical path to disease mitigation.
AB - The revolution in scientific innovation, driven by the engines of enabling
technologies, is increasingly capable of deconstructing complex disease processes
for the express purpose of reconstructing patient-specific solutions. These
revelations in biological mechanisms provide the pressure points of opportunity
for radical discovery and development to advance modern health care. Principles
of mechanism-based discovery and their translation into therapeutic algorithms
will, however, be challenged in the near term by emerging global public health
crises that currently have no immediate solutions: chronic diseases, obesity,
antibiotic-resistant infections, dementia, depression. The threat of these
pandemics (multiplied in an increasingly aging population), the global burden of
disease they represent, and their worldwide assault on human capital underscore
the importance of continued and accelerated investments in science-propelled
practice advancement, converting new knowledge into delivery of tangible health
solutions. In that context, this annual issue of CPT on therapeutics innovations
highlights remarkable recent successes in the discovery-development paradigm
translating molecular innovations into diagnostic and therapeutic realities that
transform the management of disease, impacting global health.
PMID- 24352146
TI - Microbial life in the Lake Medee, the largest deep-sea salt-saturated formation.
AB - Deep-sea hypersaline anoxic lakes (DHALs) of the Eastern Mediterranean represent
some of the most hostile environments on our planet. We investigated microbial
life in the recently discovered Lake Medee, the largest DHAL found to-date. Medee
has two unique features: a complex geobiochemical stratification and an absence
of chemolithoautotrophic Epsilonproteobacteria, which usually play the primary
role in dark bicarbonate assimilation in DHALs interfaces. Presumably because of
these features, Medee is less productive and exhibits reduced diversity of
autochthonous prokaryotes in its interior. Indeed, the brine community almost
exclusively consists of the members of euryarchaeal MSBL1 and bacterial KB1
candidate divisions. Our experiments utilizing cultivation and [(14)C]
assimilation, showed that these organisms at least partially rely on reductive
cleavage of osmoprotectant glycine betaine and are engaged in trophic
cooperation. These findings provide novel insights into how prokaryotic
communities can adapt to salt-saturated conditions and sustain active metabolism
at the thermodynamic edge of life.
PMID- 24352152
TI - Preconditioning with recombinant high-mobility group box 1 protein protects the
kidney against ischemia-reperfusion injury in mice.
AB - A preconditioning effect occurs when exposure to a nonharmful quantity of a
mediator of injury provides protection against injury upon subsequent reexposure.
High-mobility group box 1 (HMGB1) protein, an endogenous ligand for Toll-like
receptor (TLR) 4, is a TLR4-dependent mediator of kidney ischemia-reperfusion
injury. Here we determined whether preconditioning with recombinant HMGB1 can
block kidney ischemia-reperfusion injury, whether this effect is TLR4 dependent
and, if so, how preconditioning downregulates TLR signaling. Wild-type mice
pretreated with rHMGB1 before ischemia were protected against kidney ischemia
reperfusion injury, indicated by lower serum creatinine, less tubular damage,
less tubulointerstitial neutrophil and macrophage infiltration, and less tubular
epithelial cell apoptosis versus control mice. Gene expression of TLR-downstream
cytokines and chemokines in ischemia-reperfusion injury kidney were also
significantly reduced. While TLR4 and TLR2 knockout mice were protected against
kidney ischemia-reperfusion injury, HMGB1 preconditioning provided additional
protection to TLR2 but not TLR4 knockout mice. The protective effect of rHMGB1
preconditioning involved Siglec-G upregulation, a negative regulator of HMGB1
mediated TLR4 pathway activation. Thus, preconditioning with rHMGB1 affords
significant protection from TLR4-dependent kidney ischemia-reperfusion injury,
indicating therapeutic potential.
PMID- 24352153
TI - Disparate effects of single endothelin-A and -B receptor blocker therapy on the
progression of renal injury in advanced renovascular disease.
AB - We hypothesized that chronic specific endothelin-A (ET-A) receptor blockade
therapy would reverse renal dysfunction and injury in advanced experimental
renovascular disease. To test this, unilateral renovascular disease was induced
in 19 pigs, and after 6 weeks, single-kidney hemodynamics and function was
quantified in vivo using computed tomography. All pigs with renovascular disease
were divided such that seven were untreated, seven were treated with ET-A
blockers, and five were treated with ET-B blockers. Four weeks later, all pigs
were restudied in vivo, and then killed and ex vivo studies performed on the
stenotic kidney to quantify microvascular density, remodeling, renal oxidative
stress, inflammation, and fibrosis. Renal blood flow, glomerular filtration rate,
and redox status were significantly improved in the stenotic kidney after ET-A
but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal
microvascular rarefaction and diminished remodeling, which was accompanied by a
marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but
not ET-B blockade ameliorated renal injury in pigs with advanced renovascular
disease by stimulating microvascular proliferation and decreasing the progression
of microvascular remodeling, renal inflammation, and fibrosis in the stenotic
kidney. These effects were functionally consequential as ET-A blockade improved
single kidney microvascular endothelial function, renal blood flow, and
glomerular filtration rate, and decreased albuminuria.
PMID- 24352154
TI - Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol
accumulation.
AB - Metabolic syndrome (MetSyn) is a major health concern and associates with the
development of kidney disease. The mechanisms linking MetSyn to renal disease
have not been fully elucidated but are known to involve hyperuricemia,
inflammation, and fibrosis. Since the innate immune receptor Nlrp3 is an
important mediator of obesity and inflammation, we sought to determine whether
Nlrp3 is involved in the development of MetSyn-associated nephropathy by giving
wild-type or Nlrp3-knockout mice a Western-style compared to a normal diet or
water without or with fructose. A plausible driver of pathology, the Nlrp3
dependent cytokine IL-1beta was not increased in the kidney. Interestingly, Nlrp3
dependent renal cholesterol accumulation, another well-known driver of renal
pathology, was enhanced during MetSyn. We also determined the role of Nlrp3 and
fructose-fortified water on the development of MetSyn and kidney function since
fructose is an important driver of obesity and kidney disease. Surprisingly,
fructose did not induce MetSyn but, irrespective of this, did induce Nlrp3
dependent renal inflammation. The presence of Nlrp3 was crucial for the
development of Western-style diet-induced renal pathology as reflected by the
prevention of renal inflammation, fibrosis, steatosis, microalbuminuria, and
hyperuricemia in the Nlrp3-knockout mice. Thus, Nlrp3 may mediate renal pathology
in the context of diet-induced MetSyn.
PMID- 24352155
TI - High altitude may alter oxygen availability and renal metabolism in diabetics as
measured by hyperpolarized [1-(13)C]pyruvate magnetic resonance imaging.
AB - The kidneys account for about 10% of the whole body oxygen consumption, whereas
only 0.5% of the total body mass. It is known that intrarenal hypoxia is present
in several diseases associated with development of kidney disease, including
diabetes, and when renal blood flow is unaffected. The importance of deranged
oxygen metabolism is further supported by deterioration of kidney function in
patients with diabetes living at high altitude. Thus, we argue that reduced
oxygen availability alters renal energy metabolism. Here, we introduce a novel
magnetic resonance imaging (MRI) approach to monitor metabolic changes associated
with diabetes and oxygen availability. Streptozotocin diabetic and control rats
were given reduced, normal, or increased inspired oxygen in order to alter tissue
oxygenation. The effects on kidney oxygen metabolism were studied using
hyperpolarized [1-(13)C]pyruvate MRI. Reduced inspired oxygen did not alter renal
metabolism in the control group. Reduced oxygen availability in the diabetic
kidney altered energy metabolism by increasing lactate and alanine formation by
23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the
increased prevalence and severity of nephropathy in patients with diabetes at
high altitudes may originate from the increased sensitivity toward inspired
oxygen. This increased lactate production shifts the metabolic routs toward
hypoxic pathways.
PMID- 24352156
TI - Ethnic differences in bone and mineral metabolism in healthy people and patients
with CKD.
AB - Several studies have shown racial differences in the regulation of mineral
metabolism, in the acquisition of bone mass and structure of individuals. In this
review, we examine ethnic differences in bone and mineral metabolism in normal
individuals and in patients with chronic kidney disease. Black individuals have
lower urinary excretion and increased intestinal calcium absorption, reduced
levels of 25(OH)D, and high levels of 1.25(OH)2D and parathyroid hormone (PTH).
Body phosphorus concentration is higher and the levels of FGF-23 are lower than
in whites. Mineral density and bone architecture are better in black individuals.
These differences translate into advantages for blacks who have stronger bones,
less risk of fractures, and less cardiovascular calcification. In the United
States of America, the prevalence of kidney disease is similar in different
ethnic groups. However, black individuals progress more quickly to advanced
stages of kidney disease than whites. This faster progression does not translate
into increased mortality, higher in whites, especially in the first year of
dialysis. Some ethnicity-related variations in mineral metabolism persist when
individuals develop CKD. Therefore, black patients have lower serum calcium
concentrations, less hyperphosphatemia, low levels of 25(OH)D, higher levels of
PTH, and low levels of FGF-23 compared with white patients. Bone biopsy studies
show that blacks have greater bone volume. The rate of fractures and
cardiovascular diseases are also less frequent. Further studies are required to
better understand the cellular and molecular bases of these racial differences in
bone mineral metabolism and thus better treat patients.
PMID- 24352157
TI - The accuracy of predicting cardiovascular death based on one compared to several
albuminuria values.
AB - Albuminuria is a well-documented predictor of cardiovascular (CV) mortality.
However, day-to-day variability is substantial, and there is no consensus on the
number of urine samples required for risk prediction. To resolve this we followed
9158 adults from the population-based Nord-Trondelag Health Study for 13 years
(Second HUNT Study). The predictive performance of models for CV death based on
Framingham variables plus 1 versus 3 albumin-creatinine ratio (ACR) was assessed
in participants who provided 3 urine samples. There was no improvement in
discrimination, calibration, or reclassification when using ACR as a continuous
variable. Difference in Akaike information criterion indicated an uncertain
improvement in overall fit for the model with the mean of 3 urine samples.
Criterion analyses on dichotomized albuminuria information sustained 1 sample as
sufficient for ACR levels down to 1.7 mg/mmol. At lower levels, models with 3
samples had a better overall fit. Likewise, in survival analyses, 1 sample was
enough to show a significant association to CV mortality for ACR levels above 1.7
mg/mmol (adjusted hazard ratio 1.37; 95% CI 1.15-1.63). For lower ACR levels, 2
or 3 positive urine samples were needed for significance. Thus, multiple urine
sampling did not improve CV death prediction when using ACR as a continuous
variable. For cutoff ACR levels of 1.0 mg/mmol or less, additional urine samples
were required, and associations were stronger with increasing number of samples.
PMID- 24352158
TI - Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA
in human urine.
AB - Micro RNAs (miRNAs) have been shown to circulate in biological fluids and are
enclosed in vesicles such as exosomes; they are present in urine and represent a
noninvasive methodology to detect biomarkers for diagnostic testing. The low
abundance of RNA in urine creates difficulties in its isolation, of which
exosomal miRNA is a small fraction, making downstream RNA assays challenging.
Here, we investigate methods to maximize exosomal isolation and RNA yield for
next-generation deep sequencing. Upon characterizing exosomal proteins and total
RNA content in urine, several commercially available kits were tested for their
RNA extraction efficiency. We subsequently used the methods with the highest
miRNA content to profile baseline miRNA expression using next-generation deep
sequencing. Comparisons of miRNA profiles were also made with exosomes isolated
by differential ultracentrifugation methodology and a commercially available
column-based protocol. Overall, miRNAs were found to be significantly enriched
and intact in urine-derived exosomes compared with cell-free urine. The presence
of other noncoding RNAs such as small nuclear and small nucleolar RNA in the
exosomes, in addition to coding sequences related to kidney and bladder
conditions, was also detected. Our study extensively characterizes the RNA
content of exosomes isolated from urine, providing the potential to identify
miRNA biomarkers in human urine.
PMID- 24352159
TI - Interactions of gaseous HNO3 and water with individual and mixed alkyl self
assembled monolayers at room temperature.
AB - The major removal processes for gaseous nitric acid (HNO3) in the atmosphere are
dry and wet deposition onto various surfaces. The surface in the boundary layer
is often covered with organic films, but the interaction of gaseous HNO3 with
them is not well understood. To better understand the factors controlling the
uptake of gaseous nitric acid and its dissociation in organic films, studies were
carried out using single component and mixtures of C8 and C18 alkyl self
assembled monolayers (SAMs) attached to a germanium (Ge) attenuated total
reflectance (ATR) crystal upon which a thin layer of SiOx had been deposited. For
comparison, diffuse reflectance infrared Fourier transform spectrometry (DRIFTS)
studies were also carried out using a C18 SAM attached to the native oxide layer
on the surface of silicon powder. These studies show that the alkyl chain length
and order/disorder of the SAMs does not significantly affect the uptake or
dissociation/recombination of molecular HNO3. Thus, independent of the nature of
the SAM, molecular HNO3 is observed up to 70-90% relative humidity. After
dissociation, molecular HNO3 is regenerated on all SAM surfaces when water is
removed. Results of molecular dynamics simulations are consistent with
experiments and show that defects and pores on the surfaces control the uptake,
dissociation and recombination of molecular HNO3. Organic films on surfaces in
the boundary layer will certainly be more irregular and less ordered than SAMs
studied here, therefore undissociated HNO3 may be present on surfaces in the
boundary layer to a greater extent than previously thought. The combination of
this observation with the results of recent studies showing enhanced photolysis
of nitric acid on surfaces suggests that renoxification of deposited nitric acid
may need to be taken into account in atmospheric models.
PMID- 24352160
TI - Prognostic factors for outcome in pediatric probable lesional frontal lobe
epilepsy with an unknown cause (cryptogenic).
AB - The outcomes of children with cryptogenic seizures most probably arising from the
frontal lobe are difficult to predict. We retrospectively collected data on 865
pediatric patients with epilepsy. In 78 patients with cryptogenic frontal lobe
epilepsy, the age at first seizure was inversely correlated with the outcome,
including the degree of intellectual disability/developmental delay (P = .002)
and seizure frequency (P = .02) after adequate treatment. Intellectual disability
was more prevalent in children with a first seizure at 0 to 3 years old (P =
.002), and seizures were more frequent in those with a first seizure at 0 to 6
years old than at 7 to 16 years old (P = .026). For pediatric cryptogenic frontal
lobe epilepsy, the age at first seizure is important and inversely correlated
with outcome, including seizure frequency and intellectual disability.
PMID- 24352161
TI - De novo SCN8A mutation identified by whole-exome sequencing in a boy with
neonatal epileptic encephalopathy, multiple congenital anomalies, and movement
disorders.
AB - Epileptic encephalopathies represent a clinically and genetically heterogeneous
group of disorders, majority of which are of unknown etiology. We used whole
exome sequencing of a parent-offspring trio to identify the cause of early
infantile epileptic encephalopathy in a boy with neonatal seizures, movement
disorders, and multiple congenital anomalies who died at the age of 17 months
because of respiratory illness and identified a de novo heterozygous missense
mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type
VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger
sequencing. Because the clinical phenotype associated with SCN8A mutations has
previously been identified only in a few patients with or without epileptic
seizures, these data together with our results suggest that mutations in SCN8A
can lead to early infantile epileptic encephalopathy with a broad phenotypic
spectrum. Additional investigations will be worthwhile to determine the
prevalence and contribution of SCN8A mutations to epileptic encephalopathies.
PMID- 24352162
TI - A new self-report quality of life questionnaire for children with neuromuscular
disorders: presentation of the instrument, rationale for its development, and
some preliminary results.
AB - Improvement of quality of life in neuromuscular disorders is a primary objective,
both in management of affected children and in the context of therapeutic trials.
Quality of life is a subjective concept and it is crucial to gather information
directly from patients. We created the SOLE Questionnaire for NMDs, a new
instrument designed to investigate quality of life in children with neuromuscular
disorders, and tested it in a study population of 78 patients and in 81 healthy
children aged 5 to 13 years. The SOLE Questionnaire, characterized by a visual
and neutral approach, was well received, practical, rapid to administer, and able
to discriminate between patients and controls. We also confirmed the presence of
disagreement about children's quality of life between children and their parents.
We suggest that our new approach could help to improve understanding of quality
of life in children with neuromuscular disorders.
PMID- 24352164
TI - The contribution of major diagnostic causes to socioeconomic differences in
disability retirement.
AB - OBJECTIVES: The aim of this study was twofold: to investigate socioeconomic
differences in disability retirement (DR) due to major diseases and find out
which diseases contribute most to the overall socioeconomic differences in DR.
METHODS: The data were longitudinal register-based (10% sample of Finns) from
Statistics Finland. These data included 258 428 participants aged 35-64 years
during the follow-up. The participants were employed or unemployed before the
follow-up period 1997-2010. Of all participants, 14 303 men and 13 188 women
ended up in DR during the follow-up. Socioeconomic status was categorized into
upper- and lower-class non-manual employees, manual workers, and self-employed
persons. Cox models were used to estimate hazard ratios for DR due to different
diseases. RESULTS: Compared to upper-class non-manual employees, DR was
especially high for manual workers whose retirement diagnoses included
psychoactive substance use, musculoskeletal diseases (MSD), or cardiovascular
diseases. Socioeconomic differences in DR were stronger for younger age groups
and men versus women. For females and males, the largest part of the excess DR
among manual workers compared to upper-class non-manual employees was due to MSD.
In the age group 54-64 years, the contribution of MSD to the total excess was
>50% among male manual workers and 75% among female manual workers. Excess DR due
to mental disorders concerned only 35-54-year-old manual workers (among 23% men
and 26% women). CONCLUSION: The contribution of MSD to the total excess DR among
lower socioeconomic groups was large. Prevention of MSD among manual workers
would likely reduce socioeconomic differences in DR.
PMID- 24352165
TI - Ultrafast viscous water flow through nanostrand-channelled graphene oxide
membranes.
AB - Pressure-driven ultrafiltration membranes are important in separation
applications. Advanced filtration membranes with high permeance and enhanced
rejection must be developed to meet rising worldwide demand. Here we report
nanostrand-channelled graphene oxide ultrafiltration membranes with a network of
nanochannels with a narrow size distribution (3-5 nm) and superior separation
performance. This permeance offers a 10-fold enhancement without sacrificing the
rejection rate compared with that of graphene oxide membranes, and is more than
100 times higher than that of commercial ultrafiltration membranes with similar
rejection. The flow enhancement is attributed to the porous structure and
significantly reduced channel length. An abnormal pressure-dependent separation
behaviour is also reported, where the elastic deformation of nanochannels offers
tunable permeation and rejection. The water flow through these hydrophilic
graphene oxide nanochannels is identified as viscous. This nanostrand-channelling
approach is also extendable to other laminate membranes, providing potential for
accelerating separation and water-purification processes.
PMID- 24352167
TI - Practice GAPS: preventing and detecting antibodies to anti-tumor necrosis factor
agents: gaps in practice or in evidence?
PMID- 24352166
TI - Worldwide genetic variation at the 3' untranslated region of the HLA-G gene:
balancing selection influencing genetic diversity.
AB - The HLA-G (human leukocyte antigen-G) molecule plays a pivotal role in immune
tolerance by inhibiting different cell subsets involved in both innate and
adaptive immunity. Besides its primary function in maintaining the maternal-fetal
tolerance, HLA-G has been involved in a wide range of pathological conditions
where it can be either favorable or detrimental to the patient, depending on the
nature of the pathology. Although several studies have demonstrated the utmost
importance of the 3' untranslated region (3'UTR) in the HLA-G expression profile,
limited data exist on the sequence variability of this gene region in human
populations. In this study, we characterized the genetic diversity and haplotype
structure of the HLA-G 3'UTR by resequencing 444 individuals from three sub
Saharan African populations and retrieving data from the 1000 Genomes project and
the literature. A total of 1936 individuals representing 21 worldwide populations
were combined and jointly analyzed. Our data revealed a high level of nucleotide
diversity, an excess of intermediate frequency variants and an extremely low
population differentiation, strongly supporting a history of balancing selection
at this locus. The 14-bp insertion/deletion polymorphism was further pointed out
as the likely target of selection, emphasizing its potential role in the post
transcriptional regulation of HLA-G expression.
PMID- 24352168
TI - "Smart" DNA interfaces.
AB - This review focuses on surface-grafted DNA, and its use as a molecular building
block that exploits its unique properties as a directional (poly)anion that
exhibits molecular recognition. The selected examples highlight innovative
applications of DNA at surfaces and interfaces ranging from molecular diagnostics
and sequencing to biosensing.
PMID- 24352170
TI - Simeprevir approved for hepatitis C virus infection.
PMID- 24352171
TI - President signs compounding law.
PMID- 24352172
TI - Policy journal cites barriers to pharmacists' role on primary care teams.
PMID- 24352176
TI - Reducing daptomycin expenditures by standardizing doses.
PMID- 24352177
TI - Implementation and expansion of a pharmacist-managed spirometry service.
PMID- 24352178
TI - Prevention and treatment of chemotherapy-induced peripheral neuropathy.
AB - PURPOSE: The prevention and treatment of chemotherapy-induced peripheral
neuropathy (CIPN) are reviewed. SUMMARY: A number of agents, including
amifostine, glutathione, and vitamin E, were evaluated as prevention strategies
for CIPN, with no agent demonstrating efficacy. Calcium and magnesium are
effective for the prevention of CIPN; however, concerns regarding reduced
chemotherapy efficacy linger. Venlafaxine, a serotonin-norepinephrine reuptake
inhibitor (SNRI), was evaluated for the prevention of neuropathy in a randomized,
double-blind, placebo-controlled Phase III trial of patients receiving an
oxaliplatin-based regimens every two weeks and demonstrated significantly less
acute neurotoxicity compared with the control group. Treatment options for CIPN
include reducing the dosage of the chemotherapy, changing the chemotherapy, and
treating CIPN with adjunct therapy. Adjunct therapy with topical agents,
tricyclic antidepressants, and anticonvulsants, such as pregabalin and
gabapentin, have shown limited efficacy. However, a randomized, double-blind,
crossover, Phase III trial of duloxetine versus placebo for the treatment of CIPN
caused by paclitaxel or oxaliplatin found that patients treated with duloxetine
60 mg daily had a larger average decrease in pain score than those receiving
placebo, regardless of the chemotherapy used. CONCLUSION: Calcium and magnesium
infusions and venlafaxine are effective in preventing CIPN but are not routinely
used because of concerns related to decreased chemotherapy efficacy. Adjunct
treatment options for CIPN include a topical analgesic, a tricyclic
antidepressant, an anticonvulsant, or an SNRI. Duloxetine is more effective than
placebo in treating oxaliplatin- or paclitaxel-induced CIPN, is well tolerated,
and should be considered to be a first-line treatment option for CIPN.
PMID- 24352179
TI - Implementation of a pharmacist-supervised outpatient diabetes treatment clinic.
AB - PURPOSE: The implementation of a pharmacist-managed Veterans Affairs (VA) clinic
for high-risk patients with type 2 diabetes is described, including a review of
first-year performance data. SUMMARY: As part of VA's ongoing initiative to
improve chronic disease management by creating multidisciplinary Patient-Aligned
Care Teams (PACTs) that include clinical pharmacy specialists, an outpatient
diabetes treatment clinic was implemented at a VA site in Massachusetts. Operated
two days weekly, the clinic provides continuity of care between physician visits
by applying standard protocols and procedures for insulin therapy; oral
medication and insulin doses are adjusted according to self-monitored blood
glucose values and other health data transmitted by patients via telephone or
secure messaging system. The clinic pharmacist monitors patients' progress toward
attainment of glycosylated hemoglobin (HbA1c) goals and provides frequent
followup and education to prevent hypoglycemia. During its first year of
operation, the clinic enrolled 160 veterans. Among 85 patients included in a
three-month review of outcomes data, the mean +/- S.D. HbA1c concentration
declined by more than one percentage point (from 9.12% +/- 1.41% to 7.94% +/-
1.18%). Further HbA1c improvements were documented in a subset of 46 patients
followed for six months after clinic enrollment, with no episodes of severe
hypoglycemia. CONCLUSION: An outpatient clinic successfully integrated a
pharmacist into a multidisciplinary PACT focused on veterans with poorly
controlled type 2 diabetes. The clinic's initial experience suggests that
frequent pharmacist interventions have a positive impact in promoting appropriate
insulin use in this high-risk patient population.
PMID- 24352180
TI - Risk of hepatotoxicity associated with fluoroquinolones: a national case-control
safety study.
AB - PURPOSE: Results of a pharmacoepidemiologic evaluation of fluoroquinolone
associated hepatotoxicity using national hospital admissions data on Veterans
Affairs (VA) patients are reported. METHODS: In a retrospective case-control
study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA
facility during a 6.5-year period (January 2002-June 2008) were identified. After
the exclusion of patients whose records indicated known causes of hepatotoxicity
or a history of liver disease, a subgroup of 7,862 patients with exposure to
fluoroquinolone antibiotics in the six months prior to hospital admission were
matched with nonexposed controls (n = 45,512). Conditional logistic regression
was used to assess the overall and drug-specific risks of hepatotoxicity in the
case group, controlling for comorbidities, concomitant use of known hepatotoxic
medications, and other variables. RESULTS: After adjusting for confounders,
logistic regression analysis indicated a significantly higher overall risk of
hepatotoxicity development among fluoroquinolone users relative to controls (odds
ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk
analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin,
and moxifloxacin) indicated a significant association between ciprofloxacin use
and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when
considered as independent variables, levofloxacin use and moxifloxacin use were
not significantly associated with hepatotoxicity risk. CONCLUSION: The findings
of a national VA safety study suggested an increased hepatotoxicity risk
asssociated with fluoroquinolone exposure in the study population.
PMID- 24352181
TI - Medicare annual wellness visits conducted by a pharmacist in an internal medicine
clinic.
AB - PURPOSE: The clinical and financial outcomes of an initial Medicare annual
wellness visit (AWV) administered by a clinical pharmacist practitioner (CPP) in
an academic internal medicine clinic are described. SUMMARY: As a result of the
Patient Protection and Affordable Care Act, Medicare Part B allows for coverage
of an AWV at no cost to eligible beneficiaries. The AWV is directed at health
prevention, disease detection, and coordination of screening available to
beneficiaries. CPPs are pharmacists who are recognized as advanced practice
providers in the state of North Carolina and are authorized to administer AWVs.
Eligible Medicare beneficiaries at least 65 years of age in an academic internal
medicine clinic were mailed invitations to schedule an AWV. Patients who
scheduled an AWV were mailed a packet to complete before the visit. During the
visit, the packet was reviewed and interventions were made based on prespecified
criteria derived from evidence-based medicine recommendations. After completion
of the AWV, patients were provided with a detailed and individualized prevention
plan. Between August 2011 and May 2012, 98 patients attended an AWV, all
performed by the same CPP. The average time from check in to checkout for all
patients was 73 minutes. The CPP made 441 interventions during these 98 visits,
averaging 4.5 interventions per AWV completed. All initial AWVs were reimbursable
up to a maximum of $159.38 per visit. CONCLUSION: A Medicare AMV administered by
a CPP resulted in a wide variety of patient interventions and reimbursement for
services provided.
PMID- 24352182
TI - Implementation of a pharmacy technician-centered medication reconciliation
program at an urban teaching medical center.
AB - PURPOSE: An inpatient medication reconciliation (MR) program emphasizing pharmacy
technicians' role in the MR process is described. SUMMARY: As part of quality
improvement (QI) efforts focused on MR-related adverse drug events, an urban
academic medical center in New Jersey implemented a pharmacy technician-centered
MR (PTMR) program targeting patients on its internal medicine, oncology, and
clinical decision units. The program is staffed by five full- or part-time
technicians who are trained in MR methods and work under direct pharmacist
supervision, interviewing newly admitted patients and using other information
sources (e.g., community pharmacies, physician offices, nursing facilities) to
compile an accurate and complete medication list. About 30% of all patients
admitted to the hospital are served by the PTMR program, which averages more than
500 cases each month. During one three-month period, 1748 discrepancies on
preadmission medication lists were identified, most of which involved the
omission of drugs (65.7% of cases) and incorrect information on dose and
frequency of use (14.4%). Efforts to overcome resource constraints and other
program challenges (e.g., privacy concerns, delays in community pharmacy
transmittal of prescription refill lists) are ongoing. To date, most research on
PTMR has been conducted in emergency departments or perioperative settings;
experience with the PTMR program suggests that this approach can be applied in
other hospital areas to improve MR processes and, ultimately, enhance
pharmacotherapy safety and effectiveness across transitions of care. CONCLUSION:
Based on experience, providers' perspectives, and QI data, the PTMR program is an
effective method to obtain, document, and communicate accurate MR data for
patients at this institution.
PMID- 24352183
TI - Medication error reporting in rural critical access hospitals in the North Dakota
Telepharmacy Project.
AB - PURPOSE: Results of a study of medication "quality-related events" (QREs) at
critical access hospitals (CAHs) participating in a telepharmacy project are
reported. METHODS: Rates and types of medication QREs (i.e., all types of drug
therapy problems requiring pharmacist intervention) were evaluated at 17 CAHs
receiving telepharmacy services from a central order-entry site in the North
Dakota Telepharmacy Project (NDTP). During the 17-month study, remote pharmacists
used telepharmacy technology to review medication orders prepared at the CAH
sites, identify and address QREs, and code clinical interventions. The collected
data were analyzed via chi-square testing. RESULTS: Cumulative monthly medication
orders at the CAH study sites ranged from a low of 12,535 in the first month of
the study to a high of 18,257. Monthly rates of visual medication verification
and clinical intervention ranged from 8.0% to 14.2% and from 1.3% to 3.1%,
respectively. Overall, the most frequently identified QREs were transcription
errors, which accounted for 2,389 interventions (43.3%); 2,078 interventions
(37.7%) targeted prescribing-related QREs. The most frequently cited intervention
codes were for dosage adjustments (n = 547), deep venous thrombosis prophylaxis
(n = 437), pharmacokinetic consultation (n = 268), renal dosing (n = 182), and
the prevention of minor (n = 148) and major (n = 94) adverse drug events.
CONCLUSION: The study results indicate that the NDTP telepharmacy model is
effective in identifying and resolving QREs in CAHs. The use of the telepharmacy
services increased over the study period, suggesting that CAH practitioners
became more comfortable using the technology on a regular basis to enhance
patient safety.
PMID- 24352184
TI - Major publications in the critical care pharmacotherapy literature: February 2012
through February 2013.
AB - PURPOSE: Recent impactful additions to the professional literature on the role of
pharmacotherapy in treating the critically ill are summarized. SUMMARY: An
unusually large number of updated practice guidelines and other publications with
broad critical care pharmacotherapy ramifications appeared in the primary
biomedical literature during the designated review period (February 2012-February
2013). Hundreds of relevant articles were evaluated by the Critical Care
Pharmacotherapy Literature Update group (CCPLU), a national group of pharmacists
who routinely monitor 25 peer-reviewed journals for emerging evidence that
pertains to rational medication use in the intensive care unit (ICU) setting.
From among those articles, 64 were summarized for dissemination to CCPLU members;
the 8 publications deemed to have the greatest utility for critical care
practitioners, as determined by CCPLU through a voting process, were selected for
inclusion in this review, with preference given to evidence meeting high
standards of methodological quality. The summaries presented here include (1)
important new recommendations on management of pain, agitation, and delirium in
critically ill patients, (2) a comprehensive update of a practice guideline
issued in 2008 by the Surviving Sepsis Campaign, (3) novel strategies for the
prevention and/or treatment of hyperglycemia in critical care, and (4) reports on
clinical trials of promising alternative methods of sedation for use in weaning
patients from mechanical ventilation. CONCLUSION: This review provides synopses
of practice guidelines and other recent additions to the professional literature
pertaining to rational medication use in the ICU practice setting.
PMID- 24352185
TI - Tunable single-photon frequency conversion in a Sagnac interferometer.
AB - Quantum information carriers like photons might be manipulated, stored and
transmitted in different quantum systems. It is important to integrate those
systems efficiently. The capability of converting photons from one wavelength to
another wavelength is a key requirement for combining the photons in
telecommunications band for quantum transmission and the photons in near-visible
band for quantum storage. Here, we investigate the tunable single-photon
frequency conversion in the five-level emitter-Sagnac interferometer system. We
show that the efficient single-photon conversion can be achieved in this scheme,
at the same time, the frequencies of the input and output photons can be tuned in
a large scale by controlling the frequencies and Rabi frequencies of the external
driving fields. The realization of this scheme may lead to the efficient
combination of quantum storage system with the quantum communication system.
PMID- 24352186
TI - Ordered Au nanocrystals on a substrate formed by light-induced rapid annealing.
AB - Light-induced rapid annealing (LIRA) is a widely used method to modify the
morphology and crystallinity of noble metal nanoparticles, and the nanoparticles
generally evolve into nanospheres. It is rather challenging to form faceted Au
nanocrystals on a substrate using LIRA. Here the formation of spatially ordered
Au nanocrystals using a continuous wave infrared laser is reported, assisted by a
metamaterial perfect absorber. Faceted Au nanocrystals in truncated-octahedral or
multi-twinned geometries can be obtained. The evolution of morphology and
crystallinity of the Au nanoparticles during laser annealing is also revealed,
where the crystal grain growth and the surface melting are shown to play key
roles in nanocrystal formation. The evolution of morphology also gives the
freedom of tuning the absorption spectrum of the metamaterial absorber. These
findings provide a novel way for tailoring the morphology and crystallinity of
metallic nanoparticles and may pave the way to fabricate refined nano-devices in
many potential applications for optics, electronics, catalysis, surface-chemistry
and biology.
PMID- 24352187
TI - Engineering plasmonic metal colloids through composition and structural design.
AB - The optical properties of metal nanomaterials are determined by a set of
parameters that include composition, particle size and shape, overall
architecture, and local environment. This Tutorial Review examines the influence
of each of these factors on the localized surface plasmon resonance of colloidal
metal nanoparticles. This examination is paralleled with a discussion of the
advances which have enabled the synthesis of structurally defined metal
nanomaterials, as these samples serve as the best platforms for elucidating the
fundamental properties of plasmonic colloids. Based on the analysis of such
samples, five guidelines are presented to aid the rational design and synthesis
of new metal nanostructures for advanced applications in nanomedicine, energy,
chemical sensing, and colloidal plasmonics in general.
PMID- 24352188
TI - A proposed scoring system for assessment of severity of illness in pediatric
acute hematogenous osteomyelitis using objective clinical and laboratory
findings.
AB - BACKGROUND: Severity of illness in children with acute hematogenous osteomyelitis
(AHO) is variable, ranging from mild, requiring short-duration antibiotic therapy
without surgery, to severe, requiring intensive care, multiple surgeries and
prolonged hospitalization. This study evaluates severity of illness among
children with AHO using clinical and laboratory findings. METHODS: Fifty-six
children with AHO, consecutively treated in 2009, were retrospectively studied.
Objective clinical, radiographic and laboratory parameters related to severity of
illness were gathered for each child. A physician panel was assembled to rank
order objective clinical parameters, review clinical data and classify each child
as mild, moderate or severe. Statistically significant parameters correlated with
length of hospitalization were utilized to devise a severity of illness score and
applied to the cohort of children for internal validation. RESULTS: The physician
panel had perfect or substantial agreement regarding 7 parameters (ICU admission,
intubation, pulmonary involvement, venous thrombosis, multifocal infection,
surgeries and febrile days on antibiotics). Parameters that significantly
correlated with total length of stay included: C-reactive protein values at
admission (P < 0.0001), 48 hours (P < 0.0001) and 96 hours (P < 0.0002); febrile
days on antibiotics (P < 0.0001); admission respiratory rate (P = 0.023) and
evidence of disseminated disease (P = 0.016). A scoring system, derived from
selected parameters, significantly differentiated children with AHO on the basis
of causative organism, intensive care admission, surgeries, length of
hospitalization, complications and physician panel assessment. CONCLUSIONS:
Severity of illness score for AHO, derived from preliminary clinical and
laboratory findings, is useful stratifying children with this disease. LEVEL OF
EVIDENCE: Prognostic Level II.
PMID- 24352189
TI - Long-term effectiveness of combination antiretroviral therapy and prevalence of
HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.
AB - OBJECTIVE: To determine the long-term outcomes of treatment and prevalence of
genotypic drug resistance in children and adolescents on combination
antiretroviral therapy. METHODS: A cross-sectional study (September 2009 to
October 2010) in which clinical, immunologic and virologic outcomes were assessed
at a single-study visit and through patient records in a cohort of HIV-infected
children and adolescents. Risk factors for clinical and immunologic responses and
virologic outcome were evaluated using logistic regression, and the accuracy of
clinical and immunologic criteria in identifying virologic failure was assessed.
RESULTS: Four hundred twenty-four patients were enrolled with a median age of
10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral
therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17%
underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5
years had CD4 >=350 cells/mm and in 74% (95% confidence interval: 62-84) of
younger children CD4% was >=25. CD4 values and age at combination antiretroviral
therapy initiation were independently associated with CD4 outcomes; 124 (29%) had
HIV-1 RNA >=1000 copies/mL, with no significant predictors. Sensitivity for
weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15
42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52
samples tested, >=1 mutations were observed in 91% (nucleoside reverse
transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase
inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16
(31%) and >=3 thymidine analogue-associated mutations in 7 (13%). CONCLUSION:
Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of
children with treatment failure in whom genotyping was performed demonstrated
multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells
were good indicators for treatment failure.
PMID- 24352190
TI - Revisiting pneumonia and exposure status in infants born to HIV-infected mothers.
AB - HIV-exposed uninfected infants are an increasing population. Past analyses have
often categorized these infants as uninfected leading to inaccurate conclusions.
We present a HIV exposure, rather than infection, based reanalysis of treatment
failure among children with pneumonia to show that failure odds among HIV-exposed
uninfected infants are intermediate between their unexposed and infected
counterparts. Additional prospective studies aimed at better understanding this
population are needed.
PMID- 24352191
TI - Impact of the single-dose immunization strategy against hepatitis A in Argentina.
AB - BACKGROUND: After a country wide outbreak occurred during 2003-2004, 1 dose of
hepatitis A vaccine was introduced into Argentinian regular immunization schedule
for all children aged 12 months in June 2005. The aim of this study was to assess
the impact of this novel intervention. METHODS: A longitudinal analysis was done
of hepatitis A virus (HAV) infection rates reported to the National
Epidemiological Surveillance System from 2000 to 2011. Occurrence of fulminant
hepatic failure (FHF) and liver transplantation cases up to 2011 were also
assessed. Incidence rates and clinical impact were compared between pre- and
postvaccination periods (2000-2002 vs. 2006-2011). Notification rates were also
compared by age groups and geographical regions. RESULTS: Since 2006, an abrupt
decline was observed in HAV infection rates, as well as in FHF and liver
transplantation cases. The mean incidence rate of 7.9/100,000 in the
postvaccination period represents a reduction of 88.1% (P < 0.001) when compared
with the prevaccination period. Neither FHF nor liver transplantation due to HAV
infection were observed since March 2007. Decline in incidence rates was evident
in all geographical regions and all age groups but was higher in the
prevaccination most affected areas and in young children. Although an absolute
decrease was observed for cases and rates in all age groups, since 2006, a higher
proportion of cases was observed in people >14 years of age. CONCLUSIONS: The
single-dose vaccination strategy has been highly effective for controlling HAV
infection in all age groups till now in Argentina. Long-term surveillance will be
critical to document the sustained success of this unique intervention.
PMID- 24352192
TI - Linezolid use in hospitalized children.
AB - We used the Pediatric Health Information System to evaluate linezolid use among
hospitalized children. From 2003 to 2007, use increased 5-fold, including wide
interhospital variation, then stabilized through 2011. Linezolid was responsible
for 3% of total antibiotic expenditures. Children with respiratory, oncologic or
transplant conditions were the most frequently treated with linezolid.
PMID- 24352194
TI - Pulmonary gas exchange after foam sclerotherapy.
PMID- 24352193
TI - Functional anatomy of an allosteric protein.
AB - Synaptic receptors are allosteric proteins that switch on and off to regulate
cell signalling. Here, we use single-channel electrophysiology to measure and map
energy changes in the gating conformational change of a nicotinic acetylcholine
receptor. Two separated regions in the alpha-subunits--the transmitter-binding
sites and alphaM2-alphaM3 linkers in the membrane domain--have the highest phi
values (change conformation the earliest), followed by the extracellular domain,
most of the membrane domain and the gate. Large gating-energy changes occur at
the transmitter-binding sites, alpha-subunit interfaces, the alphaM1 helix and
the gate. We hypothesize that rearrangements of the linkers trigger the global
allosteric transition, and that the hydrophobic gate unlocks in three steps. The
mostly local character of side-chain energy changes and the similarly high phi
values of separated domains, both with and without ligands, suggest that gating
is not strictly a mechanical process initiated by the affinity change for the
agonist.
PMID- 24352195
TI - Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced
DNA vaccine delivery.
AB - Dendritic cells (DC) targeting vaccines require high efficiency for uptake,
followed by DC activation and maturation. We used magnetic vectors comprising
polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles, with
hyaluronic acid (HA) of different molecular weights (<10 and 900 kDa) to reduce
cytotoxicity and to facilitate endocytosis of particles into DCs via specific
surface receptors. DNA encoding Plasmodium yoelii merozoite surface protein 1-19
and a plasmid encoding yellow fluorescent gene were added to the magnetic
complexes with various % charge ratios of HA: PEI. The presence of magnetic
fields significantly enhanced DC transfection and maturation. Vectors containing
a high-molecular-weight HA with 100% charge ratio of HA: PEI yielded a better
transfection efficiency than others. This phenomenon was attributed to their
longer molecular chains and higher mucoadhesive properties aiding DNA
condensation and stability. Insights gained should improve the design of more
effective DNA vaccine delivery systems.
PMID- 24352196
TI - Health insurance coverage and adverse experiences with physician availability:
United States, 2012.
AB - KEY FINDINGS: Data from the National Health Interview Survey, 2012. In the 12
months prior to interview, 2.4% of people in the U.S. had problems finding a
general doctor, 2.1% had been told that a doctor would not accept them as new
patients, and 2.9% had been told that a doctor did not accept their health care
coverage. People under age 65 who had public coverage only were more likely than
those with private insurance to have these three types of adverse experiences
with physician availability. Adults aged 18-64 who were uninsured were more
likely than privately insured adults to have trouble finding a general doctor or
be told that a doctor would not accept them as new patients. Adults aged 65 and
over with Medicare only were as likely as those with both Medicare and private
insurance to have these experiences with physician availability. Rates of private
insurance and public coverage have been increasing (1,2). As coverage and
utilization increase, a growing concern is the availability of health care
providers to meet patient needs (3). Almost 90% of general physicians accept new
patients with private insurance, but less than 75% accept new patients with
public coverage (e.g., Medicare, Medicaid), and the proportion of specialists
accepting new patients with Medicare or Medicaid is declining (4). While most
studies approach access from a provider perspective, this report examines the
percentage of people who had each of three adverse experiences with physician
availability in the past 12 months. Estimates were produced by age group and
health insurance status using data from the 2012 National Health Interview Survey
(NHIS).
PMID- 24352198
TI - High hyperdiploidy among adolescents and adults with acute lymphoblastic
leukaemia (ALL): cytogenetic features, clinical characteristics and outcome.
AB - High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of
acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as
well as outcome of HeH among adolescents and adults have not been thoroughly
investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in
the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients
aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)
positive and -negative cases, but Ph-positive patients were older. The
cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar,
although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph
positive HeH patients did not have an inferior overall survival compared with Ph
negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was
associated with a superior outcome in Ph-negative patients, whereas +5 and +20
were associated with an inferior outcome in Ph-positive and Ph-negative patients,
respectively. All three markers retained significance in multivariate analysis
adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95%
CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54)
(P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all
ages and displays outcome heterogeneity according to chromosomal gain.
PMID- 24352200
TI - TCTP directly regulates ATM activity to control genome stability and organ
development in Drosophila melanogaster.
AB - Translationally controlled tumour protein (TCTP) is implicated in growth
regulation and cancer. Recently, human TCTP has been suggested to play a role in
the DNA damage response by forming a complex with ataxia telangiectasia-mutated
(ATM) kinase . However, the exact nature of this interaction and its roles in
vivo remained unclear. Here, we utilize Drosophila as an animal model to study
the nuclear function of Drosophila TCTP (dTCTP). dTCTP mutants show increased
radiation sensitivity during development as well as strong genetic interaction
with dATM mutations, resulting in severe defects in developmental timing, organ
size and chromosome stability. We identify Drosophila ATM (dATM) as a direct
binding partner of dTCTP and describe a mechanistic basis for dATM activation by
dTCTP. Altogether, this study provides the first in vivo evidence for direct
modulation of dATM activity by dTCTP in the control of genome stability and organ
development.
PMID- 24352199
TI - Rethinking the diagnostic criteria of polycythemia vera.
AB - The aim of this review is to critically address the validity and clinical
applicability of three major diagnostic classification systems for polycythemia
vera (PV), that is, those proposed by the Polycythemia Vera Study Group (PVSG),
the British Committee for Standards in Haematology (BCSH) and the World Health
Organization (WHO). Special focus is on which one of the three red cell
parameters (hemoglobin-HB, hematocrit-HCT and red cell mass-RCM) should be used
as the diagnostic hallmark of PV. The revised BCSH employed a persistently raised
HCT level as the first diagnostic criterion in combination with the presence of a
JAK2V617F mutation. On the other hand, the WHO classification used a raised HB
value as a surrogate for increased RCM in association with molecular markers and
for the first time, the bone marrow (BM) morphology was included as a minor
criterion. Ongoing controversy and discussion regards the use of certain
threshold values for HCT and HB as surrogates for RCM as well as the existence of
prodromal-latent disease, so-called masked PV (mPV). It has been shown that mPV
can be recognized in patients not meeting the required HB or HCT threshold levels
by both the WHO and BCSH criteria. These cases present with the same baseline
clinical features as overt PV but present worsened survival. A critical
reappraisal of the WHO criteria may suggest either to reduce the thresholds for
HB or to consider HCT values as major diagnostic criterion, as in the BCSH, in
association with JAK2V617F mutation. The clinical utility of using HCT as
reference variable is supported also by results of clinical trials which
explicitly recommend to use the HCT threshold for monitoring treatment. In
questionable cases as in mPV, BM biopsy examinations should be mandated together
with mutation analysis.
PMID- 24352201
TI - [Atypical femoral fractures in bisphosphonate therapy].
AB - Bisphosphonates (BP) play an important role in the therapy of osteoporosis as
they effectively reduce the risk of fractures. Atypical femoral fractures (AFF)
have recently been described as an adverse effect of BP treatment. We present 3
women under therapy with BP, who had five AFF, among these three complete and two
incomplete fractures. The incidence of AFF under therapy with BP is low, and the
benefit regarding reduction of spinal fractures and fractures of the proximal
femur is much higher than the risk for an AFF.
PMID- 24352204
TI - Density functional theory studies of methyl dissociation on a Ni(111) surface in
the presence of an external electric field.
AB - To provide a basis for understanding the reactive processes on nickel surfaces at
fuel cell anodes, we investigate the influence of an external electric field on
the dehydrogenation of methyl species on a Ni(111) surface using density
functional theory calculations. The structures, adsorption energies and reaction
barriers for all methyl species dissociation on the Ni(111) surface are
identified. Our results show that the presence of an external electric field does
not affect the structures and favorable adsorption sites of the adsorbed species,
but causes the adsorption energies of the CHx species at the stable site to
fluctuate around 0.2 eV. Calculations give an energy barrier of 0.692 eV for CH3*
-> CH2* + H*, 0.323 eV for CH2* -> CH* + H* and 1.373 eV for CH* -> C* + H*.
Finally, we conclude that the presence of a large positive electric field
significantly increases the energy barrier of the CH* -> C* + H* reaction more
than the other two reactions, suggesting that the presence of pure C atoms on
Ni(111) are impeded in the presence of an external positive electric field.
PMID- 24352202
TI - [One-year outcomes for proximal femoral fractures: Posthospital analysis of
mortality and care levels based on health insurance data].
AB - BACKGROUND: Proximal femur fractures are common and treatment is expensive. The
aim of the present study was - after matching of hospital and health insurance
data - to evaluate the influence of early operation on certain outcome
parameters. Data from a German health insurance were used to identify then
influence of the day of operation after admittance on the rate of mortality,
decubitus, and revision surgery during the hospital stay and on the care level of
the patients up to 1 year and in some cases longer after operation. MATERIALS AND
METHODS: In all, 7905 patients were included. The descriptive data, specifying
the given population, described the hospital stay (occurrence, surgical
procedures, early complications, secondary diagnoses, length of stay) and the
course of patient recovery up to 1 year after the hospital stay (care level, late
complications). The calculated data (analytical statistics) give correlations
evaluating the influence of the length of the preoperative hospital stay on the
outcome parameters mentioned above. Risk adjustment was performed by using
secondary diagnoses. RESULTS: The study included more women (mean age 81.5
years). Most common was the femoral neck fracture. Of the operations 77% were
carried out on the first day after admission; dominating procedures were
intramedullary nails and prostheses. Most common secondary diagnoses were
diabetes, dementia, ischemic heart disease, and chronic heart insufficiency.
Descriptive data revealed 6% early as well as late complications. In all, 50% of
patients had a higher care level after operation. Almost 40% of patients changed
from outpatient care to inpatient care. The time interval between admission and
operation negatively influenced all outcome parameters. The relative risk to die,
to develop decubitus, or to receive early revision was increased by approximately
one third when patients were operated on later than the first day after
admission. A total of 3172 patients died during the study period. Mortality after
operation reached 9.9% within 30 days and 26.9% at 1 year. The mortality of
patients operated after the first day was increased by more than 6% compared to
patients treated within the first 24 h. CONCLUSION: The present study clearly
presents the importance of analysis of routine records after discharge and it
demonstrates that longer periods up to 1 year and more can be evaluated. The data
show that a longer time period between hospital admission and operation
negatively influences all outcome parameters. The care data give impressive
evidence for a significant loss of quality of life and the importance of intense
postoperative rehabilitation.
PMID- 24352205
TI - A highly selective chemodosimeter for fast detection and intracellular imaging of
Hg2+ ions based on a dithiocarbamate-isothiocyanate conversion in aqueous
ethanol.
AB - A new naphthalene diimide-dithiocarbamate based fluorescence probe was
synthesized and its fluorogenic behavior towards various metal ions was studied.
Upon addition of various metal ions, the probe afforded an irreversible change
only with Hg(2+) ions in aqueous-ethanol media (4 : 1 v/v) with a fourfold
enhancement of the fluorescence (Phi = 0.03 -> 0.11) along with a distinct 43 nm
blue shift of the emission maxima. The mechanism of the chemodosimetric behavior
of the probe has been attributed to a Hg(2+) induced transformation of a weakly
fluorescent dithiocarbamate to a highly fluorescent isothiocyanate which has been
characterized by a number of spectroscopic techniques and a crystal structure.
Intracellular detection of Hg(2+) ions was achieved using the probe.
PMID- 24352206
TI - Superficial femoral artery perforator flap: anatomical study of a new flap and
clinical cases.
AB - BACKGROUND: The medial thigh has been infrequently studied as a donor site for
pedicled or free flaps. In their previous studies, the authors observed a direct
cutaneous branch from the superficial femoral artery. This study aimed to
investigate the anatomy and potential possibility for flap elevation (the
midmedial thigh flap) on this direct branch of the superficial femoral vessels.
METHODS: Circumferential adipocutaneous thigh flaps were harvested from 14 fresh
adult cadaver legs. The direct cutaneous branch from the superficial femoral
vessels was located between the sartorius and gracilis muscles. Pedicle location,
diameter, and length and position of the great saphenous vein and saphenous nerve
were recorded. A flap based on this vessel was designed. Height, width, and
surface of the skin paddle were recorded. Three-dimensional computed tomographic
angiography was used to analyze the area of cutaneous territory supplied by the
studied perforator. RESULTS: The pedicle was located at an average distance of
22.79 +/- 1.55 cm below the pubic tubercle on the medial axis of the thigh, and
it was found in 100 percent of dissections. It was always located between the
sartorius and gracilis muscles, with a mean diameter of 2.82 +/- 0.69 mm and mean
length of 4.79 +/- 0.52 cm. The average area of skin perfused was 182.24 cm,
located preferentially distal and posterior to the perforator pedicle. Two
clinical cases illustrate the feasibility of the midmedial thigh perforator flap.
CONCLUSIONS: The superficial femoral artery perforator flap appears to be
reliable and has a constant vascular anatomy. Donor-site morbidity is low,
resulting in only a vertical scar on the medial thigh. CLINICAL QUESTION/LEVEL OF
EVIDENCE: Therapeutic, V.
PMID- 24352207
TI - Treatment of infantile hemangiomas with propranolol: clinical guidelines.
AB - BACKGROUND: Infantile hemangioma is a vascular tumor and requires treatment in
lesions manifested by potentially dangerous symptoms. Several publications have
reported that involution of infantile hemangioma could be accelerated by
propranolol but have used only invalidated subjective measures of assessment. The
authors aimed to objectively validate the aesthetic results after propranolol
treatment for infantile hemangioma, and to produce a therapy protocol, including
optimal timing for introduction, pretreatment preparation, dosage, frequency of
visits, duration, and patient safety. METHODS: For the nonrandomized comparative
cohort study, the authors enrolled 60 patients treated with propranolol. Medical
two-dimensional photographs, taken before and after treatment, were subjectively
analyzed by three plastic surgery consultants and objectively analyzed with a
computer program. Aesthetic results were analyzed using the following parameters:
subjective overall outcome, subjective color fading, and objective color fading.
Reliability of subjective and objective methods was quantified and compared, as
described with accuracy and repeatability. Volumetric parameters were obtained
from three-dimensional scans taken before and after treatment and objectively
analyzed with a computer program. Numerous patients' data were recorded from the
medical notes. RESULTS: This study proved high efficiency of propranolol in
treatment of infantile hemangioma, as assessed with the objective measures for
the first time. The authors outlined an optimal treatment protocol, including
introduction, dosage, duration, and cessation of therapy. CONCLUSIONS:
Propranolol is an effective, well-tolerated, and safe first-line treatment for
proliferative hemangioma. Therapy should begin early, continue with the target
dosage of 2 mg/kg/day in three divided doses through the proliferative phase of
infantile hemangioma, and be stopped gradually. CLINICAL QUESTION/LEVEL OF
EVIDENCE: Therapeutic, IV.
PMID- 24352208
TI - Operative treatment of peripheral lymphedema: a systematic meta-analysis of the
efficacy and safety of lymphovenous microsurgery and tissue transplantation.
AB - BACKGROUND: The purpose of this study was to quantify the efficacy and safety of
microsurgery for lymphedema through a systematic meta-analysis, which has not
been described before. METHODS: A literature search was conducted to identify all
articles involving microsurgical treatment of lymphedema. Studies meeting
criteria for inclusion were rated on methodologic quality based on the American
Society of Plastic Surgeons levels of evidence. Demographic information, cause of
lymphedema, and surgical technique were recorded. Quantitative change in
lymphedema and perioperative complications were noted. RESULTS: Twenty-seven
studies were included, with 24 offering level IV evidence and three offering
level III evidence. Lymphovenous shunt procedures were performed in 22 studies
and lymph node transplantation was performed in five. Excess circumference was
reduced by 48.8 +/- 6.0 percent, and absolute circumference was reduced by 3.31
+/- 0.73 cm. Studies reporting change in volume demonstrated reduction in excess
volume by 56.6 +/- 9.1 percent, and absolute volume was reduced by 23.6 +/- 2.1
percent. The incidence of no improvement in lymphedema postoperatively was 11.8
percent, and 91.2 percent of patients reported subjective improvement.
Approximately 64.8 percent of patients discontinued compression garments at
follow-up. Complications included operative-site infection (4.7 percent),
lymphorrhea (7.7 percent), reexploration for flap congestion (2.7 percent), and
additional procedures (22.6 percent). CONCLUSIONS: Operative interventions for
peripheral lymphedema appear to provide consistent quantitative improvements
postoperatively, with a relatively wide safety margin. Lymph node transplantation
may provide better outcomes compared with lymphovenous shunt, but well-designed
head-to-head comparisons are needed to evaluate this further. CLINICAL
QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
PMID- 24352210
TI - Classifying deformities of the columella base in rhinoplasty.
AB - BACKGROUND: Although much has been published with regard to the columella
assessed on the frontal and lateral views, a paucity of literature exists
regarding the basal view of the columella. The objective of this study was to
evaluate the spectrum of columella deformities and devise a working
classification system based on underlying anatomy. METHODS: A retrospective study
was performed of 100 consecutive patients who presented for primary rhinoplasty.
The preoperative basal view photographs for each patient were reviewed to
determine whether they possessed ideal columellar aesthetics. Patients who had
deformity of their columella were further scrutinized to determine the most
likely underlying cause of the subsequent abnormality. RESULTS: Of the 100
patient photographs assessed, only 16 (16 percent) were found to display ideal
norms of the columella. The remaining 84 of 100 patients (84 percent) had some
form of aesthetic abnormality and were further classified based on the most
likely underlying cause. Type 1 deformities (caudal septum and/or spine)
constituted 18 percent (18 of 100); type 2 (medial crura), 12 percent (12 of
100); type 3 (soft tissue), 6 percent (six of 100); and type 4 (combination), 48
percent (48 of 100). CONCLUSIONS: Deformities may be classified according to the
underlying cause, with combined deformity being the most common. Use of the
herein discussed classification scheme will allow surgeons to approach this
region in a comprehensive manner. Furthermore, use of such a system allows for a
more standardized approach for surgical treatment.
PMID- 24352211
TI - Achieving patient satisfaction in abdominally based free flap breast
reconstruction: correlation with body mass index subgroups and weight loss.
AB - BACKGROUND: The goal of this study was to evaluate the relationship between body
mass index, preoperative weight loss, and patient satisfaction in breast
reconstruction with abdominally based free flaps. METHODS: A custom survey with
overall, breast, and abdomen questions was sent to patients who underwent
abdominally based free flap breast reconstruction over the past 4 years. Clinical
data were collected for patients who returned surveys. Data analysis was
performed based on body mass index and percentage weight loss before surgery.
RESULTS: One hundred seventy-nine surveys were sent. Ninety-two patients (51.4
percent) responded. Normal weight patients versus overweight patients did not
have statistically significant differences in any satisfaction scores. Overweight
patients had higher overall satisfaction (p = 0.01), breast-specific satisfaction
(p = 0.01), and abdomen-specific satisfaction (p = 0.02) compared with obese
patients. Normal weight patients had higher breast-specific satisfaction (p =
0.05) and abdomen-specific satisfaction (p = 0.03) scores compared with obese
patients. Patients with significant preoperative weight loss were more satisfied
with feeling of breasts in clothes (p = 0.01), social appearance (p = 0.05), and
current abdominal appearance (p = 0.01) compared with patients with moderate
preoperative weight loss. Overall, breast- and abdomen-specific satisfaction
scores decreased with increase in pannus thickness. CONCLUSIONS: Patient
satisfaction with abdominally based free flap breast reconstruction was highest
in patients with normal body mass index and lowest in obese patients. Overweight
or obese patients should be encouraged to participate in healthy weight loss
programs to achieve improved postoperative satisfaction. CLINICAL QUESTION/LEVEL
OF EVIDENCE: Therapeutic, IV.
PMID- 24352212
TI - Inflammatory response and survival of pedicled abdominal flaps in a rat model
after perivascular application of botulinum toxin type A.
AB - BACKGROUND: In addition to the numerous applications of botulinum toxin type A,
the authors have documented improvements in surgical flap survival through
vasoactive effects. This study aimed to investigate its effect on the expression
of inflammatory mediators. METHODS: In 54 male Sprague-Dawley rats, cutaneous
flaps based on the superficial epigastric vessels were elevated. Botulinum toxin
type A, lidocaine, or saline was administered to the vascular pedicle. After 1,
2, and 7 days, mRNA expression for tumor necrosis factor-alpha, interleukin-1,
and vascular endothelial growth factor-165 was compared along with flap survival.
RESULTS: Vascular endothelial growth factor-165 mRNA expression was lower in the
botulinum toxin type A group compared with (1) the saline group at days 1 and 2
(p < 0.01) and (2) the lidocaine group at day 2 (p < 0.05). The expression of
interleukin-1 was significantly less at each time point in the botulinum toxin
type A group compared with the lidocaine group (p < 0.02), and at day 2 compared
with the saline group (p < 0.01). Tumor necrosis factor-alpha mRNA expression in
the botulinum toxin type A group was lower at 2 days and 7 days compared with
both other groups (p < 0.04). Finally, both the botulinum toxin type A and
lidocaine groups had a greater survival area (p < 0.05) compared with the saline
group. CONCLUSION: The presence of botulinum toxin type A in the postsurgical
flap microenvironment augments tissue perfusion and its inflammatory response
and, ultimately, survival.
PMID- 24352209
TI - Economic analysis of revision amputation and replantation treatment of finger
amputation injuries.
AB - BACKGROUND: The purpose of this study was to perform a cost-utility analysis to
compare revision amputation and replantation treatment of finger amputation
injuries across a spectrum of injury scenarios. METHODS: The study was conducted
from the societal perspective. Decision tree models were created for the
reference case (two-finger amputation injury) and seven additional injury
scenarios for comparison. Inputs included cost, quality of life, and probability
of each health state. A Web-based time trade-off survey was created to determine
quality-adjusted life-years for health states; 685 nationally representative
adult community members were invited to participate in the survey. Overall cost
and quality-adjusted life-years for revision amputation and replantation were
calculated for each decision tree. An incremental cost-effectiveness ratio was
calculated if a treatment was more costly but more effective. RESULTS: The
authors had a 64 percent response rate (n = 437). Replantation treatment had
greater costs and quality-adjusted life-years compared with revision amputation
in all injury scenarios. Replantation of single-digit injuries had the highest
incremental cost-effectiveness ratio ($136,400 per quality-adjusted life-year
gained). Replantation of three- and four-digit amputation injuries had relatively
low cost-to-benefit ratios ($27,100 and $23,800 per quality-adjusted life-year,
respectively). Replantation for distal thumb amputation had a relatively low
incremental cost-effectiveness ratio ($26,300 per quality-adjusted life-year)
compared with replantation of nonthumb distal amputations ($60,200 per quality
adjusted life-year). CONCLUSIONS: The relative cost per quality-adjusted life
year gained with replantation treatment varied greatly among the injury
scenarios. Situations in which indications for replantation are debated had
higher cost per quality-adjusted life-year gained. This study highlights
variability in value for replantation among different injury scenarios.
PMID- 24352213
TI - Telmisartan activates endogenous peroxisome proliferator-activated receptor-delta
and may have anti-fibrotic effects in human mesangial cells.
AB - Telmisartan, an angiotensin II receptor type 1 blocker (ARB), was recently
reported to promote lipolysis in mice by acting as a peroxisome proliferator
activated receptor (PPAR)-delta activator, although in clinical studies, it has
also been recognized to activate PPAR-gamma as a major cause of its pleiotropic
actions. The aim of this study was to investigate whether telmisartan activates
endogenous PPAR-delta and thereby exerts anti-fibrotic effects in human mesangial
cells (HMC). Immunohistochemical analysis of human renal biopsy specimens
revealed that PPAR-delta protein was detected in the HMC of glomeruli with
moderately proliferative changes. In the HMC, both GW0742, an authentic PPAR
delta agonist, and telmisartan enhanced PPAR response element (PPRE)-luciferase
activity dose dependently, and these increases were blunted by GSK0660, a
specific PPAR-delta antagonist, but not by GW9662, a PPAR-gamma antagonist.
Telmisartan also upregulated the expression of PPAR-delta target genes related to
fatty acid oxidation; that is, heart type-fatty acid-binding protein and
uncoupling protein-2. These effects were inhibited by both PPAR-delta antagonism
and PPAR-delta gene silencing. Transforming growth factor-beta1 (TGF-beta1)
increased the expression of plasminogen activator inhibitor-1 (PAI-1), TGF-beta1
and collagen IV. The PAI-1 expression was mediated, at least in part by the
phosphorylation of extracellular signal-regulated kinases (ERKs). Telmisartan
suppressed TGF-beta1-stimulated PAI-1 and collagen IV expression and ERK
phosphorylation, and these effects were weakened by PPAR-delta antagonism,
whereas eprosartan, a non-PPAR activating ARB, did not affect TGF-beta1
stimulated PAI-1 expression. These results indicate that in HMC telmisartan
activates endogenous PPAR-delta and may prevent TGF-beta1-induced fibrotic
changes by reducing ERK phosphorylation in a PPAR-delta-dependent manner, and
thus, might be useful for treating hypertensive patients with renal and metabolic
disorders.
PMID- 24352215
TI - Two cases of imported tungiasis with severe Staphylococcus aureus superinfection.
PMID- 24352214
TI - Recombinant AAV as a platform for translating the therapeutic potential of RNA
interference.
AB - RNA interference has become a ubiquitous biological tool, and is being harnessed
for therapeutic purposes as well. Therapeutic posttranscriptional gene silencing
takes advantage of the endogenous RNAi pathway through delivery of either
chemically synthesized siRNAs, or transgenes expressing hairpin-based inhibitory
RNAs (e.g., shRNAs and artificial miRNAs). RNAi has expanded the field of viral
gene therapy from gene replacement to gene knockdown. Here, we review various
noncoding RNAs such as shRNAs, miRNAs, and miRNA decoys which can be utilized for
therapeutic applications when expressed from recombinant adeno-associated vectors
(AAV), and present examples of their basic design. In addition the basis of
exploiting cellular miRNA profiles for detargeting AAV expression from specific
cells is described. Finally, an overview of AAV-mediated RNAi preclinical studies
is presented, and current RNAi-based clinical trials are reviewed.
PMID- 24352216
TI - A new cyclic supramolecular Zn(II) complex derived from a N2O2 oxime chelate
ligand with luminescence mechanochromism.
AB - A new Zn(II) complex was synthesized based on a new Salen-type tetradentate N2O2
bisoxime chelate ligand (H2L) derived from 1-phenyl-3-methyl-4-benzoyl-5
pyrazolone (PMBP) and 1,2-bis(aminooxy)ethane. Single-crystal X-ray diffraction
analysis reveals that the structure of the Zn(II) complex features a three
dimensional (3D) cyclic supramolecular system via intermolecular hydrogen bonds.
Moreover, the solid-state photoluminescent properties demonstrate that the Zn(II)
complex exhibits unusual luminescence mechanochromism tuned by CH3OH.
PMID- 24352217
TI - Extreme extensibility of copper foil under compound forming conditions.
AB - A copper foil with an extreme extensibility up to 43,684% was obtained without
any intermediate annealing by means of asynchronous rolling with high tension. It
was found that under the combination of compression, shearing and tension, the
copper foil represents a wonderful phenomenon. As the reduction increases, the
specimen hardness increases up to a peak value 138 HV0.05 when the foil thickness
rolled to around 100 MUm, and then it decreases down to 78 HV0.05 when the foil
thickness rolled to the final size 19 MUm. It tells us that the strain-softening
effect occurs when the foil thickness is rolled down to a threshold level. The
experimental results bring us some fresh ideas different with the traditional
understanding on the strain-hardening mechanism of metals, which provides an
experimental basis to establish the forming mechanism of the thin foil.
PMID- 24352218
TI - Macrovascular involvement in a child with atypical hemolytic uremic syndrome.
AB - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a disorder of the
complement system which leads to thrombotic microangiopathy. It is caused by
either acquired or hereditary defects in the activation or regulation of the
alternative complement pathway and is therefore considered to be a disease of
local complement dysregulation in microvasculature with predominantly renal
involvement. However, extrarenal manifestations are observed in approximately one
fifth of aHUS patients, with the myocardium and central nervous system (CNS)
being involved most often. Additionally, there have been a few reports of aHUS
with cerebral artery stenoses or periphereal gangrene, suggesting the possibility
of 'macrovascular' involvement in aHUS. CASE-DIAGNOSIS/TREATMENT: We present a
child with early onset aHUS and a C3 gain-of-function mutation who developed
cerebral artery stenoses, leading ultimately to death due to a massive stroke 9
days after successful renal transplantation under prophylactic eculizumab
treatment. Similar cases described in the literature are also briefly summarized.
CONCLUSIONS: The disease course in our patient with aHUS confirms that
dysregulated complement activation can induce arterial steno-occlusive lesions in
the absence of acute episodes of HUS. Further studies are required to document
the frequency of such macrovascular complications and the role of eculizumab
treatment in preventing their development and progression.
PMID- 24352219
TI - Monitoring of acute myeloid leukemia patients after allogeneic stem cell
transplantation employing semi-automated CD34+ donor cell chimerism analysis.
AB - Determination of donor chimerism profiles in blood or bone marrow from patients
with allogeneic stem cell transplantation (SCT) is useful for monitoring
engraftment or predicting relapse, when specific molecular markers are lacking.
CD34+ donor cell chimerism (DCC) analysis in peripheral blood samples from CD34+
acute myeloid leukemia (AML) and myleodysplastic syndrome (MDS) patients proved
to be a highly sensitive diagnostic tool that is useful to detect imminent
relapse significantly earlier compared to total white blood cell donor cell
chimerism monitoring. However, flow-cytometric enrichment of CD34+ cells requires
high efforts to human resources and equipment. We present a novel semi-automated
CD34+ DCC analysis procedure-employing a magnetic cell-enrichment device, DNA
extraction, and short tandem repeat profiling-without the need for flow
cytometric cell sorting. Monitoring 85 patients with AML and MDS over a period of
4 years 24 relapses were detected. Semi-automated peripheral blood CD34+ DCC was
diminished below 80 % in all cases of systemic relapse. Significant decrease of
the CD34+ DCC value was detected 29-42 days before overt cytological relapse. Our
method provides a rapid and sensitive tool for monitoring AML and MDS patients
after allogeneic SCT with regard to engraftment and early detection of relapse.
Here, we propose a novel semi-automated procedure for CD34+ DCC analysis after
allogeneic SCT that is simple, reliable, and therefore applicable in all
hematologic laboratories.
PMID- 24352220
TI - Predictors of plasma cell disorders among African American patients: a community
practice perspective.
AB - African Americans have two- to three-fold higher incidence of multiple myeloma
and MGUS compared to other ethnic groups in the USA. Some physicians often
perform diagnostic evaluations for plasma cell disorders (PCD) in African
American patients on the basis of hematological abnormalities (thrombocytopenia,
leucopenia, etc.) even in the absence of traditional triggers such as anemia,
renal impairment, hypercalcemia, hyperglobulinemia, and lytic bone disease.
Whether these nontraditional triggers have any significant association with PCD
in African American population is not known. In addition, whether this approach
could detect more asymptomatic PCD than black population prevalence is
questionable. Moreover, the association between traditional triggers and PCD
particularly in blacks has not been clearly delineated. Hence, we have carried
out a retrospective study in an attempt to answer these questions. Two hundred
fifty-four patients were eligible. Multiple myeloma workup based on parameters
other than traditional triggers did not detect more asymptomatic PCD than what is
expected of black population prevalence (p = 0.19). Of traditional triggers, the
finding of only anemia or hyperglobulinemia seemed to be nonspecific in black
population (p = 0.17 and 0.85, respectively). However, the presence of serum
creatinine >2 mg/dL or corrected serum calcium >10.5 mg/dL or a combination of
traditional triggers appeared to be strongly predictive of PCD (odds ratio of
6.9, 4.2, and 3, respectively). The number of trigger variables was positively
correlated with the likelihood of PCD (p < 0.001). Light-chain-only PCD, renal
disease, and abnormal free light chain ratio seemed to be higher in black
patients than their white counterparts.
PMID- 24352221
TI - Sibling cases of Hailey-Hailey disease showing atypical clinical features and
unique disease course.
PMID- 24352224
TI - Ultrashort single-walled carbon nanotubes in a lipid bilayer as a new nanopore
sensor.
AB - An important issue in nanopore sensing is to construct stable and versatile
sensors that can discriminate analytes with minute differences. Here we report a
means of creating nanopores that comprise ultrashort single-walled carbon
nanotubes inserted into a lipid bilayer. We investigate the ion transport and DNA
translocation through single-walled carbon nanotube nanopores and find that our
results are fundamentally different from previous studies using much longer
single-walled carbon nanotubes. Furthermore, we utilize the new single-walled
carbon nanotube nanopores to selectively detect modified 5-hydroxymethylcytosine
in single-stranded DNA, which may have implications in screening specific genomic
DNA sequences. This new nanopore platform can be integrated with many unique
properties of carbon nanotubes and might be useful in molecular sensing such as
DNA-damage detection, nanopore DNA sequencing and other nanopore-based
applications.
PMID- 24352225
TI - Stability of Bovine viral diarrhea virus 1 nucleic acid in fetal bovine samples
stored under different conditions.
AB - Infection of pregnant cattle with both species of Bovine viral diarrhea virus
(BVDV) can result in reproductive disease that includes fetal reabsorption,
mummification, abortion, stillbirths, congenital defects affecting structural,
neural, reproductive, and immune systems, and the birth of calves persistently
infected with BVDV. Accurate diagnosis of BVDV-associated reproductive disease is
important to control BVDV at the production unit level and assessment of the cost
of BVDV infections in support of BVDV control programs. The purpose of the
current study was to examine the stability of viral nucleic acid in fetal tissues
exposed to different conditions, as measured by detection by polymerase chain
reaction. Five different types of fetal tissue, including brain, skin and muscle,
ear, and 2 different pooled organ samples, were subjected to conditions that
mimicked those that might exist for samples collected after abortions in
production settings or possible storage conditions after collection and prior to
testing. In addition, tissues were archived for 36 months at -20 degrees C and
then retested, to mimic conditions that might occur in the case of retrospective
surveillance studies. Brain tissue showed the highest stability under the
conditions tested. The impact of fecal contamination was increased following
archiving in all tissue types suggesting that, for long-term storage, effort
should be made to reduce environmental contaminants before archiving.
PMID- 24352226
TI - Choriocarcinoma-like tumor in a potbellied pig (Sus scrofa).
AB - A uterine tumor, with histological and immunohistochemical features consistent
with those of human choriocarcinoma, was identified in a 10-year-old unmated
female pot-bellied pig (Sus scrofa). The tumor showed biphasic proliferation of
cytotrophoblast-like cells and syncytiotrophoblast-like cells.
Immunohistochemically, the syncytiotrophoblast-like cells were positive for human
chorionic gonadotropin, and both types of cells were positive for cytokeratin and
negative for vimentin, octamer-binding transcription factor 4, and alpha
fetoprotein. Because syncytiotrophoblasts are absent in the normal porcine
placenta, the tumor was diagnosed as a choriocarcinoma-like tumor.
PMID- 24352227
TI - Synthesis, characterization and heterogeneous catalytic application of copper
integrated mesoporous matrices.
AB - Ordered copper integrated mesoporous silicate catalysts (CuMSC) have been
synthesized by the utilization of the amphiphilic tri-block copolymer pluronic
F127 as a structure directing agent (SDA) under acidic aqueous conditions. The
mesophase of the materials was investigated using small-angle powder X-ray
diffraction and transmission electron microscopic (TEM) image analysis. N2
adsorption-desorption studies show that the BET surface area of CuMSC (214-407
m(2) g(-1)) is lower than that of pure silica (611 m(2) g(-1)) and has smaller
average pore dimensions (4.0-5.0 nm), both prepared following the same synthetic
route. The reduction of pore size and surface area points to incorporation of
copper within the silicate network. FEG-SEM results suggest that the materials
have a plate-like morphology and are composed of very tiny nanoparticles. EDS
surface chemical analysis was utilized for the detection of the distribution of
Si, O and Cu in the matrix. The FT IR spectral study suggests the complete
removal of the surfactants from the calcined materials and the presence of Si-O
Cu bonds for high nominal contents. X-ray photoelectron spectroscopy (XPS) and UV
vis reflectance spectra show the oxidation state of copper and coordination mode,
respectively. These mesoporous materials display a good catalytic activity in the
oxidation of cyclohexane to cyclohexanone and cyclohexanol in the presence of the
green oxidant hydrogen peroxide. The maximum yield (cyclohexanone and
cyclohexanol) was ca. 29% and the TON (turnover number) was 276 under optimal
reaction conditions. The good catalytic activity could be attributed to the large
surface area and the presence of a high number of active sites located at the
surface of the material, as well as to its stability. The catalysts showed
negligible loss of activity after five cycles.
PMID- 24352228
TI - Investigation on the capability of polysulphone for measuring biologically
effective solar UV exposures.
AB - Polysulphone (PS) dosimetry is a well-known technique broadly used to assess the
erythemally effective solar UV dose received by anatomical sites (personal
exposure). We investigate the capability of PS dosimetry to convert doses
absorbed by PS badges into biologically effective solar UV exposures taking as
examples two relevant effects for human skin: erythema induction and pre-vitamin
D3 production. PS calibration curves for erythemal and pre-vitamin D3 were
distinctly determined by using an empirical relationship between the biologically
effective UV exposures and the PS absorbance change. This relationship is
parameterized by a coefficient, distinct for each of the two considered
biological effects, multiplying the same cubic polynomial function. It is shown
how the multiplying coefficient is related to the ratio between the biologically
effective and the PS weighted irradiances which is the prevailing factor
affecting the accuracy of the calibration and, consequently, the capability of PS
films for measuring biologically effective solar UV exposures. The points
addressed in this paper can be extended to other biological effects of interest
whose action spectra have some similarity with the PS film response.
PMID- 24352229
TI - Asymmetric synthesis from terminal alkenes by cascades of diboration and cross
coupling.
AB - Terminal, monosubstituted alkenes are ideal prospective starting materials for
organic synthesis because they are manufactured on very large scales and can be
functionalized via a broad range of chemical transformations. Alkenes also have
the attractive feature of being stable in the presence of many acids, bases,
oxidants and reductants. In spite of these attributes, relatively few catalytic
enantioselective transformations have been developed that transform aliphatic
alpha-olefins into chiral products with an enantiomeric excess greater then 90
per cent. With the exception of site-controlled isotactic polymerization of alpha
olefins, none of these catalytic enantioselective processes results in chain
extending carbon-carbon bond formation to the terminal carbon. Here we describe a
strategy that directly addresses this gap in synthetic methodology, and present a
single-flask, catalytic enantioselective conversion of terminal alkenes into a
number of chiral products. These reactions are facilitated by a neighbouring
functional group that accelerates palladium-catalysed cross-coupling of 1,2
bis(boronates) relative to non-functionalized alkyl boronate analogues. In tandem
with enantioselective diboration, this reactivity feature transforms alkene
starting materials into a diverse array of chiral products. We note that the
tandem diboration/cross-coupling reaction generally provides products in high
yield and high selectivity (>95:5 enantiomer ratio), uses low loadings (1-2 mol
per cent) of commercially available catalysts and reagents, offers an expansive
substrate scope, and can address a broad range of alcohol and amine synthesis
targets, many of which cannot be easily addressed with current technology.
PMID- 24352230
TI - Archaic humans: Four makes a party.
PMID- 24352231
TI - Dislocations in bilayer graphene.
AB - Dislocations represent one of the most fascinating and fundamental concepts in
materials science. Most importantly, dislocations are the main carriers of
plastic deformation in crystalline materials. Furthermore, they can strongly
affect the local electronic and optical properties of semiconductors and ionic
crystals. In materials with small dimensions, they experience extensive image
forces, which attract them to the surface to release strain energy. However, in
layered crystals such as graphite, dislocation movement is mainly restricted to
the basal plane. Thus, the dislocations cannot escape, enabling their confinement
in crystals as thin as only two monolayers. To explore the nature of dislocations
under such extreme boundary conditions, the material of choice is bilayer
graphene, the thinnest possible quasi-two-dimensional crystal in which such
linear defects can be confined. Homogeneous and robust graphene membranes derived
from high-quality epitaxial graphene on silicon carbide provide an ideal platform
for their investigation. Here we report the direct observation of basal-plane
dislocations in freestanding bilayer graphene using transmission electron
microscopy and their detailed investigation by diffraction contrast analysis and
atomistic simulations. Our investigation reveals two striking size effects.
First, the absence of stacking-fault energy, a unique property of bilayer
graphene, leads to a characteristic dislocation pattern that corresponds to an
alternating AB B[Symbol: see text]AC change of the stacking order. Second, our
experiments in combination with atomistic simulations reveal a pronounced
buckling of the bilayer graphene membrane that results directly from
accommodation of strain. In fact, the buckling changes the strain state of the
bilayer graphene and is of key importance for its electronic properties. Our
findings will contribute to the understanding of dislocations and of their role
in the structural, mechanical and electronic properties of bilayer and few-layer
graphene.
PMID- 24352232
TI - CNVs conferring risk of autism or schizophrenia affect cognition in controls.
AB - In a small fraction of patients with schizophrenia or autism, alleles of copy
number variants (CNVs) in their genomes are probably the strongest factors
contributing to the pathogenesis of the disease. These CNVs may provide an entry
point for investigations into the mechanisms of brain function and dysfunction
alike. They are not fully penetrant and offer an opportunity to study their
effects separate from that of manifest disease. Here we show in an Icelandic
sample that a few of the CNVs clearly alter fecundity (measured as the number of
children by age 45). Furthermore, we use various tests of cognitive function to
demonstrate that control subjects carrying the CNVs perform at a level that is
between that of schizophrenia patients and population controls. The CNVs do not
all affect the same cognitive domains, hence the cognitive deficits that drive or
accompany the pathogenesis vary from one CNV to another. Controls carrying the
chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2)
deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ
in the analysis, and the CNV only confers modest effects on other cognitive
traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern
consistent with both that observed during first-episode psychosis in
schizophrenia and that of structural correlates in dyslexia.
PMID- 24352238
TI - Quantum physics: An atomic SQUID.
PMID- 24352235
TI - The complete genome sequence of a Neanderthal from the Altai Mountains.
AB - We present a high-quality genome sequence of a Neanderthal woman from Siberia. We
show that her parents were related at the level of half-siblings and that mating
among close relatives was common among her recent ancestors. We also sequenced
the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the
relationships and population history of available archaic genomes and 25 present
day human genomes shows that several gene flow events occurred among
Neanderthals, Denisovans and early modern humans, possibly including gene flow
into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low
magnitude, occurred among many hominin groups in the Late Pleistocene. In
addition, the high-quality Neanderthal genome allows us to establish a definitive
list of substitutions that became fixed in modern humans after their separation
from the ancestors of Neanderthals and Denisovans.
PMID- 24352233
TI - The genome of the recently domesticated crop plant sugar beet (Beta vulgaris).
AB - Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate
climates which provides nearly 30% of the world's annual sugar production and is
a source for bioethanol and animal feed. The species belongs to the order of
Caryophylalles, is diploid with 2n = 18 chromosomes, has an estimated genome size
of 714-758 megabases and shares an ancient genome triplication with other eudicot
plants. Leafy beets have been cultivated since Roman times, but sugar beet is one
of the most recently domesticated crops. It arose in the late eighteenth century
when lines accumulating sugar in the storage root were selected from crosses made
with chard and fodder beet. Here we present a reference genome sequence for sugar
beet as the first non-rosid, non-asterid eudicot genome, advancing comparative
genomics and phylogenetic reconstructions. The genome sequence comprises 567
megabases, of which 85% could be assigned to chromosomes. The assembly covers a
large proportion of the repetitive sequence content that was estimated to be 63%.
We predicted 27,421 protein-coding genes supported by transcript data and
annotated them on the basis of sequence homology. Phylogenetic analyses provided
evidence for the separation of Caryophyllales before the split of asterids and
rosids, and revealed lineage-specific gene family expansions and losses. We
sequenced spinach (Spinacia oleracea), another Caryophyllales species, and
validated features that separate this clade from rosids and asterids.
Intraspecific genomic variation was analysed based on the genome sequences of sea
beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four
additional sugar beet accessions. We identified seven million variant positions
in the reference genome, and also large regions of low variability, indicating
artificial selection. The sugar beet genome sequence enables the identification
of genes affecting agronomically relevant traits, supports molecular breeding and
maximizes the plant's potential in energy biotechnology.
PMID- 24352240
TI - Malaria: Resistance nailed.
PMID- 24352239
TI - Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated
modification.
AB - Nucleosomes are decorated with numerous post-translational modifications capable
of influencing many DNA processes. Here we describe a new class of histone
modification, methylation of glutamine, occurring on yeast histone H2A at
position 105 (Q105) and human H2A at Q104. We identify Nop1 as the
methyltransferase in yeast and demonstrate that fibrillarin is the orthologue
enzyme in human cells. Glutamine methylation of H2A is restricted to the
nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows
that this modification is exclusively enriched over the 35S ribosomal DNA
transcriptional unit. We show that the Q105 residue is part of the binding site
for the histone chaperone FACT (facilitator of chromatin transcription) complex.
Methylation of Q105 or its substitution to alanine disrupts binding to FACT in
vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and
increased transcription at the ribosomal DNA locus. These features are
phenocopied by mutations in FACT complex components. Together these data identify
glutamine methylation of H2A as the first histone epigenetic mark dedicated to a
specific RNA polymerase and define its function as a regulator of FACT
interaction with nucleosomes.
PMID- 24352234
TI - Immunological and virological mechanisms of vaccine-mediated protection against
SIV and HIV.
AB - A major challenge for the development of a highly effective AIDS vaccine is the
identification of mechanisms of protective immunity. To address this question, we
used a nonhuman primate challenge model with simian immunodeficiency virus (SIV).
We show that antibodies to the SIV envelope are necessary and sufficient to
prevent infection. Moreover, sequencing of viruses from breakthrough infections
revealed selective pressure against neutralization-sensitive viruses; we
identified a two-amino-acid signature that alters antigenicity and confers
neutralization resistance. A similar signature confers resistance of human
immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against
variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental
mechanism of immune escape from vaccine-elicited or naturally elicited
antibodies. These analyses provide insight into the limited efficacy seen in HIV
vaccine trials.
PMID- 24352241
TI - RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.
AB - Currently, there is little evidence for a notable role of the vertebrate microRNA
(miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed
to the ease with which these viruses mutate to disrupt recognition and growth
suppression by host miRNAs. Here we report that the haematopoietic-cell-specific
miRNA miR-142-3p potently restricts the replication of the mosquito-borne North
American eastern equine encephalitis virus in myeloid-lineage cells by binding to
sites in the 3' non-translated region of its RNA genome. However, by limiting
myeloid cell tropism and consequent innate immunity induction, this restriction
directly promotes neurologic disease manifestations characteristic of eastern
equine encephalitis virus infection in humans. Furthermore, the region containing
the miR-142-3p binding sites is essential for efficient virus infection of
mosquito vectors. We propose that RNA viruses can adapt to use antiviral
properties of vertebrate miRNAs to limit replication in particular cell types and
that this restriction can lead to exacerbation of disease severity.
PMID- 24352243
TI - Cell biology: The beginning of the end.
PMID- 24352242
TI - A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.
AB - Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia
threatens malaria control and elimination activities worldwide. To monitor the
spread of artemisinin resistance, a molecular marker is urgently needed. Here,
using whole-genome sequencing of an artemisinin-resistant parasite line from
Africa and clinical parasite isolates from Cambodia, we associate mutations in
the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin
resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in
Cambodian provinces where resistance is prevalent, and the increasing frequency
of a dominant mutant K13-propeller allele correlates with the recent spread of
resistance in western Cambodia. Strong correlations between the presence of a
mutant allele, in vitro parasite survival rates and in vivo parasite clearance
rates indicate that K13-propeller mutations are important determinants of
artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular
marker for large-scale surveillance efforts to contain artemisinin resistance in
the Greater Mekong Subregion and prevent its global spread.
PMID- 24352244
TI - Men with diabetes may require more aggressive treatment for erectile dysfunction.
AB - Diabetes mellitus (DM) and erectile dysfunction (ED) are common health problems
that markedly increase in prevalence and incidence with advancing age. DM is a
known risk factor for developing ED; however, among men with ED it is unknown if
DM alters the need for more invasive therapies. We sought to determine whether DM
is associated with increased ED severity, reduced effectiveness of first-line
(oral) therapies, and therefore higher utilization of second- and third-line
therapies. The Inovus I3 database was queried to identify men with ED. Claims
were followed for 48 months. Men with incomplete follow-up data and those
diagnosed with DM after ED diagnosis were excluded from analysis. Rates of second
line (penile suppositories or injectables) and third-line (penile prostheses) ED
therapies were compared between men with and without preexisting DM. Risk of
progressing to second- and third-line therapies associated with DM was assessed
with logistic regression and Kaplan-Meier analysis. From 1 January 2002 to 31
December 2006, 136 306 men were identified with prevalent and incident ED. Among
this group, 19 236 men had DM that preceded their ED diagnosis. Men with DM were
more than 50% more likely to be prescribed secondary ED treatments over the 2
year observation period, and more than twice as likely to undergo penile
prosthesis surgery. Among a large population-based cohort of men with ED, those
with DM are more likely to require more aggressive treatments. These data suggest
that ED among men with diabetes may be less responsive to first-line treatments
(oral agents), worsen more rapidly, or both.
PMID- 24352245
TI - Association between microvascular angina and erectile dsyfunction.
AB - Although the origin of cardiac syndrome X (CSX) is still debated, endothelial
dysfunction leading to reduced coronary microvascular dilatory response and
increased coronary resistance is thought to have an important role in the
pathogenesis. Erectile dysfunction (ED) is associated with risk factors resulting
in endotelial dysfunction. Although the relationship between cardiovascular
disease and ED has been well established; the relation between CSX and ED has not
been extensively studied so far. We herein aimed to study ED in patients with
CSX. The study was designed as a prospective case-control study. Blood samples
were analyzed with respect to concentrations of low-density lipoprotein
cholesterol, high-density lipoprotein cholesterol and triglycerides. The subjects
answered the native language five-item version of the International Index of
Erectile Function Questionnaire (IIEF)-5. Each question was scored from 0 to 5
with a maximum score of 25 denoting healty subjects. We investigated the IIEF-5
score in 51 men with CSX (mean age=48.2+/-6.4 years), 53 men with demonstrated
coronary artery disease (CAD) (mean age=48.3+/-4.8 years) and 52 male controls
with normal coronary arteries (mean age=47.2+/-6.0 years). Mean IIEF-5 scores
were 19.88+/-3.07 for CSX group, 18.83+/-3.31 for CAD group and 21.40+/-2.94 for
control group. IIEF-5 scores in CSX group were found to be significantly lower
than the those of control group (P<0.001). There were no significant differences
in IIEF-5 scores between CSX and CAD groups (P=0.09). We have shown for the first
time that patients with CSX have lower IIEF-5 scores compared with controls with
normal coronary angiograms. This study suggests that ED and CSX may be different
manifestations of a common underlying vascular pathology and vasculogenic ED is
frequently seen in CSX at least as much as in CAD.
PMID- 24352247
TI - Scalp angiosarcoma presented as skin-coloured papules.
PMID- 24352246
TI - Association between body fat distribution and androgen deficiency in middle-aged
and elderly men in China.
AB - The objective of the present study was to examine the association between body
fat distribution and total testosterone (TT) and free testosterone (FT) levels
among middle-aged and elderly men. A total of 922 male residents aged 40-70 years
from a community in Shanghai, China, participated in the study. Their waist
circumference (WC), waist-height ratio (WHtR), body mass index (BMI), and TT and
FT concentrations were measured. Logistic regression models were used to estimate
testosterone deficiency risk on the basis of anthropometric indices. BMI, WC and
WHtR were all associated with TT deficiency. The participants in the highest
quartiles of above-mentioned anthropometric indices had the highest risk of TT
deficiency (BMI: odds ratio (OR)=4.40, 95% confidence interval (CI)=2.69-7.19;
WC: OR=3.47, 95% CI=2.14-5.60; WHtR: OR=2.89, 95% CI=1.76-4.76). WC and WHtR were
associated with FT deficiency. The participants in the highest quartiles had the
highest risk of FT deficiency (WC: OR=1.87, 95% CI=1.18-2.97; WHtR: OR=1.67, 95%
CI=1.04-2.66). The association between BMI and FT deficiency was not
statistically significant (OR=1.21 for the highest quartile, 95% CI=0.78-1.87).
Our study demonstrated that both general and abdominal obesity were associated
with TT deficiency, whereas only abdominal obesity was found to be associated
with FT deficiency.
PMID- 24352249
TI - Density-temperature scaling of the fragility in a model glass-former.
AB - Dynamical quantities e.g. diffusivity and relaxation time for some glass-formers
may depend on density and temperature through a specific combination, rather than
independently, allowing the representation of data over ranges of density and
temperature as a function of a single scaling variable. Such a scaling, referred
to as density-temperature (DT) scaling, is exact for liquids with inverse power
law (IPL) interactions but has also been found to be approximately valid in many
non-IPL liquids. We have analyzed the consequences of DT scaling on the density
dependence of the fragility in a model glass-former. We find the density
dependence of kinetic fragility to be weak, and show that it can be understood in
terms of DT scaling and deviations of DT scaling at low densities. We also show
that the Adam-Gibbs relation exhibits DT scaling and the scaling exponent
computed from the density dependence of the activation free energy in the Adam
Gibbs relation, is consistent with the exponent values obtained by other means.
PMID- 24352250
TI - Targeting cisplatin-resistant human tumor cells with metabolic inhibitors.
AB - PURPOSE: Although cisplatin is the drug of choice in treating lung cancer
patients, relapse and resistance is a common drawback to its clinical
effectiveness. Based on cisplatin's reported ability to interfere with numerous
cellular components, including mitochondria, we probed alterations in metabolism
in cisplatin-resistant tumor cell lines to reveal targets for overcoming this
important form of resistance. METHODS: Cisplatin-resistant lung and ovarian
cancer cell lines were used to evaluate the efficacy of metabolic inhibitors for
selectively targeting cisplatin-resistant cells under varying oxygen conditions.
RESULTS: Three cisplatin-resistant cancer cell lines expressed lower HKII protein
when compared to the respective cisplatin-sensitive cancer cell lines from which
they were derived. Under anaerobic and hypoxic conditions, treatment with the
glycolytic inhibitors 2-deoxyglucose (2-DG) and 2-fluorodeoxyglucose (2-FDG)
correlated with increased cytotoxicity and more pronounced decreases in lactate
production in cisplatin-resistant cells, indicating a greater blockage of
glycolysis. Knockdown of HKI or HKII with siRNA in the parental lung cancer cell
lines led to increased 2-FDG-induced cell death under anaerobic conditions. Under
normal oxygen conditions, blockage of either fatty acid oxidation or deprivation
of glutamine resulted in cell death in cisplatin-resistant lung cancer cell
lines. CONCLUSIONS: Altered hexokinase levels in cisplatin-resistant cancer cell
lines leads to increased sensitivity to glycolytic inhibition under anaerobic
conditions, whereas under normoxic conditions, blockage of either fatty acid
oxidation or deprivation of glutamine leads to cell death. These findings may be
clinically applicable when considering cisplatin resistance.
PMID- 24352252
TI - On phase behavior and dynamical signatures of charged colloidal platelets.
AB - Charged platelet suspensions, such as swelling clays, disc-like mineral
crystallites or exfoliated nanosheets are ubiquitous in nature. Their phase
behaviours are nevertheless still poorly understood: while some clay suspensions
form arrested states at low densities, others exhibit an equilibrium isotropic
nematic transition at moderate densities. These observations raise fundamental
questions about the influence of electrostatic interactions on the isotropic
nematic transition and the organisation of charged platelets. We investigate the
competition between anisotropic excluded-volume and repulsive electrostatic
interactions in suspensions of charged colloidal discs, by means of Monte-Carlo
simulations and characterization of the dynamics of the structures. We show that
the original intrinsic anisotropy of the electrostatic potential between charged
platelets not only rationalizes generic features of the complex phase diagram of
charged colloidal platelets such as Gibbsite and Beidellite clays, but also
predicts the existence of novel structures. Furthermore, we find evidences of a
strong slowing down of the dynamics upon increasing density.
PMID- 24352251
TI - A phase II trial of erlotinib as maintenance treatment after concurrent
chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician
Lung Cancer Group (GGCP) study.
AB - PURPOSE: This single arm, phase II study aims to evaluate the role of epidermal
growth factor receptor-tyrosine-kinase inhibitor erlotinib as maintenance therapy
following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced
non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage
IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a
standard cCRT regimen with curative intent were included. Oral erlotinib 150
mg/day was administered within 4-6 weeks after the end of the cCRT for a maximum
of 6 months if no disease progression or intolerable toxicity occurred. Primary
end point was the progression-free rate (PFR) at 6 months. Secondary end points
included time to progression (TTP) and overall survival (OS). RESULTS: Sixty-six
patients were enrolled and received maintenance treatment with erlotinib
[average: 4.5 months (95 % CI 4.0-5.0)]. PFR at 6 months was 63.5 % (41/66). With
a median follow-up of 22.7 months (95 % CI 13.5-37.1), the median TTP was 9.9
months (95 % CI 6.2-12.1), and the median OS was 24.0 months (95 % CI 17.3-48.6).
Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 %
grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3),
anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients
(7.6 %) were withdrawn due to AEs. CONCLUSIONS: Erlotinib as maintenance therapy
is an active treatment after cCRT in unselected patients with stage III NSCLC,
reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile
of maintenance erlotinib was as expected and manageable.
PMID- 24352253
TI - A case of refractory Sezary syndrome with large-cell transformation responsive to
brentuximab vedotin.
PMID- 24352256
TI - Food selection in larval fruit flies: dynamics and effects on larval development.
AB - Selecting food items and attaining a nutritionally balanced diet is an important
challenge for all animals including humans. We aimed to establish fruit fly
larvae (Drosophila melanogaster) as a simple yet powerful model system for
examining the mechanisms of specific hunger and diet selection. In two lab
experiments with artificial diets, we found that larvae deprived of either
sucrose or protein later selectively fed on a diet providing the missing
nutrient. When allowed to freely move between two adjacent food patches, larvae
surprisingly preferred to settle on one patch containing yeast and ignored the
patch providing sucrose. Moreover, when allowed to move freely between three
patches, which provided either yeast only, sucrose only or a balanced mixture of
yeast and sucrose, the majority of larvae settled on the yeast-plus-sucrose patch
and about one third chose to feed on the yeast only food. While protein (yeast)
is essential for development, we also quantified larval success on diets with or
without sucrose and show that larvae develop faster on diets containing sucrose.
Our data suggest that fruit fly larvae can quickly assess major nutrients in food
and seek a diet providing a missing nutrient. The larvae, however, probably
prefer to quickly dig into a single food substrate for enhanced protection over
achieving an optimal diet.
PMID- 24352257
TI - Design and synthesis of novel anthracene derivatives as n-type emitters for
electroluminescent devices: a combined experimental and DFT study.
AB - Six novel anthracene-oxadiazole derivatives, 4a (2-(4-(anthracen-9-yl)phenyl)-5-p
tolyl-1,3,4-oxadiazole), 4b (2-(4-(anthracen-9-yl)phenyl)-5-(4-tert-butylphenyl)
1,3,4-oxadiazole), 4c (2-(4-(anthracen-9-yl)phenyl)-5-(4-methoxyphenyl)-1,3,4
oxadiazole), 8a (2-(4-(anthracen-9-yl)phenyl)-5-m-tolyl-1,3,4-oxadiazole), 8b (2
(3-(anthracen-9-yl)phenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole) and 8c (2-(3
(anthracen-9-yl)phenyl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole) have been
synthesized and characterized for use as emitters in organic light emitting
devices (OLEDs). They show good thermal stability (T(d), 297-364 degrees C) and
glass transition temperatures (T(g)) in the range of 82-98 degrees C, as seen
from the thermo gravimetric analysis and differential scanning calorimetric
studies. The solvatochromism phenomenon and electrochemical properties have been
studied in detail using UV-Vis absorption, fluorescence spectroscopy and cyclic
voltammetry. TD-DFT calculations have been carried out to understand the
electrochemical and photophysical properties. The spatial structures of 4b and 8c
are further confirmed by X-ray diffraction analysis. Un-optimized non-doped
electroluminescent devices were fabricated using these anthracene derivatives as
emitters with the following device configuration: ITO (120 nm)/alpha-NPD (30
nm)/4a-4c or 8a-8c(35 nm)/BCP (6 nm)/Alq3 (28 nm)/LiF (1 nm)/Al (150 nm). Among
all the six compounds, 8a displays the maximum brightness of 1728 cd m(-2) and
current efficiency 0.89 cd A(-1). Furthermore, as an electron transporter, 8a
exhibited superior performance (current efficiency is 11.7 cd A(-1)) than the
device using standard Alq3 (current efficiency is 8.69 cd A(-1)), demonstrating
its high potential for employment in OLEDs. These results indicate that the new
anthracene-oxadiazole derivatives could play an important role in the development
of OLEDs.
PMID- 24352254
TI - Structural basis of AMPK regulation by small molecule activators.
AB - AMP-activated protein kinase (AMPK) plays a major role in regulating cellular
energy balance by sensing and responding to increases in AMP/ADP concentration
relative to ATP. Binding of AMP causes allosteric activation of the enzyme and
binding of either AMP or ADP promotes and maintains the phosphorylation of
threonine 172 within the activation loop of the kinase. AMPK has attracted
widespread interest as a potential therapeutic target for metabolic diseases
including type 2 diabetes and, more recently, cancer. A number of direct AMPK
activators have been reported as having beneficial effects in treating metabolic
diseases, but there has been no structural basis for activator binding to AMPK.
Here we present the crystal structure of human AMPK in complex with a small
molecule activator that binds at a site between the kinase domain and the
carbohydrate-binding module, stabilising the interaction between these two
components. The nature of the activator-binding pocket suggests the involvement
of an additional, as yet unidentified, metabolite in the physiological regulation
of AMPK. Importantly, the structure offers new opportunities for the design of
small molecule activators of AMPK for treatment of metabolic disorders.
PMID- 24352258
TI - Academics should not remain silent on hacking.
PMID- 24352270
TI - Seabed scars raise questions over carbon-storage plan.
PMID- 24352271
TI - EU fishing vote foments anger.
PMID- 24352272
TI - Quandary over Soviet croplands.
PMID- 24352273
TI - Charitable grants found lacking.
PMID- 24352274
TI - 365 days: 2013 in review.
PMID- 24352276
TI - 365 days: Nature's 10.
PMID- 24352277
TI - Chemistry: A festive ferment.
PMID- 24352279
TI - Reproducibility: Life sciences lag in stringent standards.
PMID- 24352280
TI - Policy tips: six more practical pointers.
PMID- 24352281
TI - Policy tips: heed risks of uncertainty.
PMID- 24352282
TI - Health: EU fructose claim ignores risks.
PMID- 24352283
TI - Adrienne Asch (1946-2013).
PMID- 24352284
TI - Earth science: Erosion by cooling.
PMID- 24352285
TI - Space physics: A fast lane in the magnetosphere.
PMID- 24352288
TI - Worldwide acceleration of mountain erosion under a cooling climate.
AB - Climate influences the erosion processes acting at the Earth's surface. However,
the effect of cooling during the Late Cenozoic era, including the onset of
Pliocene-Pleistocene Northern Hemisphere glaciation (about two to three million
years ago), on global erosion rates remains unclear. The uncertainty arises
mainly from a lack of consensus on the use of the sedimentary record as a proxy
for erosion and the difficulty of isolating the respective contributions of
tectonics and climate to erosion. Here we compile 18,000 bedrock
thermochronometric ages from around the world and use a formal inversion
procedure to estimate temporal and spatial variations in erosion rates. This
allows for the quantification of erosion for the source areas that ultimately
produce the sediment record on a timescale of millions of years. We find that
mountain erosion rates have increased since about six million years ago and most
rapidly since two million years ago. The increase of erosion rates is observed at
all latitudes, but is most pronounced in glaciated mountain ranges, indicating
that glacial processes played an important part. Because mountains represent a
considerable fraction of the global production of sediments, our results imply an
increase in sediment flux at a global scale that coincides closely with enhanced
cooling during the Pliocene and Pleistocene epochs.
PMID- 24352287
TI - Rapid local acceleration of relativistic radiation-belt electrons by
magnetospheric chorus.
AB - Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic
storm identified the development of peaks in electron phase space density, which
are compelling evidence for local electron acceleration in the heart of the outer
radiation belt, but are inconsistent with acceleration by inward radial diffusive
transport. However, the precise physical mechanism responsible for the
acceleration on 9 October was not identified. Previous modelling has indicated
that a magnetospheric electromagnetic emission known as chorus could be a
potential candidate for local electron acceleration, but a definitive resolution
of the importance of chorus for radiation-belt acceleration was not possible
because of limitations in the energy range and resolution of previous electron
observations and the lack of a dynamic global wave model. Here we report high
resolution electron observations obtained during the 9 October storm and
demonstrate, using a two-dimensional simulation performed with a recently
developed time-varying data-driven model, that chorus scattering explains the
temporal evolution of both the energy and angular distribution of the observed
relativistic electron flux increase. Our detailed modelling demonstrates the
remarkable efficiency of wave acceleration in the Earth's outer radiation belt,
and the results presented have potential application to Jupiter, Saturn and other
magnetized astrophysical objects.
PMID- 24352290
TI - Cardiac tissue engineering: renewing the arsenal for the battle against heart
disease.
AB - The development of therapies that lead to the regeneration or functional repair
of compromised cardiac tissue is the most important challenge facing
translational cardiovascular research today. During the last 25 years huge
efforts have been made towards restoring the physiologic functions of the heart
by means of delivering cell implants into the insulted heart, initially through
'naked cell' injections and more recently through the principle of cardiac tissue
engineering and the use of elaborate delivery systems and priming mechanisms that
include scaffolds, bioreactors or ex vivo manipulations of cells and support
structures. In this review we summarise various approaches towards cardiac repair
and highlight advances in the field of tissue engineering, ranging from a review
of cell types used, to advances that attempt to address mechanistic and
functional elements that are critical for successful restoration of the heart,
including the maintenance of the extracellular matrix through scaffoldless
cardiac sheets, strategies that promote neovascularisation and the precise micro
delivery of cell populations to form three-dimensional structures through
bioengineering methods such as microfabrication.
PMID- 24352291
TI - Night time sleep macrostructure is altered in otherwise healthy 10-year-old
overweight children.
AB - OBJECTIVE: Epidemiological evidence shows an inverse relationship between sleep
duration and overweight/obesity risk. However, there are few polysomnographic
studies that relate the organization of sleep stages to pediatric overweight
(OW). We compared sleep organization in otherwise healthy OW and normal-weight
(NW) 10-year-old children. SUBJECTS: Polysomnographic assessments were performed
in 37 NW and 59 OW children drawn from a longitudinal study beginning in infancy.
Weight and height were used to evaluate body mass index (BMI) according to
international criteria. Non-rapid eye movement (NREM) sleep (stages N1, N2 and
N3), rapid eye movement (REM) sleep (stage R) and wakefulness (stage W) were
visually scored. Sleep parameters were compared in NW and OW groups for the whole
sleep period time (SPT) and for each successive third of it using independent
Student's t-tests or nonparametric tests. The relationship between BMI and sleep
variables was evaluated by correlation analyses controlling for relevant
covariates. RESULTS: The groups were similar in timing of sleep onset and offset,
and sleep period time. BMI was inversely related to total sleep time (TST) and
sleep efficiency. OW children showed reduced TST, sleep efficiency and stage R
amount, but higher stage W amount. In analysis by thirds of the SPT, the duration
of stage N3 episodes was shorter in the first third and longer in the second
third in OW children as compared with NW children. CONCLUSIONS: Our results show
reduced sleep amount and quality in otherwise healthy OW children. The lower
stage R amount and changes involving stage N3 throughout the night suggest that
OW in childhood is associated with modifications not only in sleep duration, but
also in the ongoing night time patterns of NREM sleep and REM sleep stages.
PMID- 24352292
TI - African American women exhibit similar adherence to intervention but lose less
weight due to lower energy requirements.
AB - BACKGROUND: African American (AA) women have been shown to lose less weight than
Caucasian women in response to behavioral interventions. Our objective was to
examine adherence to intervention and metabolic factors that may explain this
difference. DESIGN AND SUBJECTS: We examined longitudinal changes in body weight
and energy expenditure (EE), and objective assessment of physical activity (PA)
and energy intake (EI) during 6 months of a weight-loss intervention program,
including prescribed calorie restriction and increased PA in 66 Caucasian and 39
AA severely obese women. Comparisons were also made in 25 Caucasian and 25 AA
women matched for initial body weight. RESULTS: The AA women lost 3.6 kg less
weight than Caucasian women. Total daily EE (TDEE) and resting metabolic rate
(RMR) adjusted for fat free mass (FFM) were significantly lower in the AA women,
whereas the decrease in RMR in response to weight loss was greater in Caucasian
women. Adherence to the prescribed PA and change in PA in response to
intervention were similar in AA and Caucasian women. Prescribed EI (1794+/-153
and 1806+/-153 kcal per day) and measured EI during intervention (2591+/-371 vs
2630+/-442 kcal per day) were nearly identical in matched AA and Caucasian women.
However, the AA women lost significantly less body weight due to lower energy
requirements (2924+/-279 vs 3116+/-340 kcal per day; P<0.04), resulting in a
lower energy deficit (333+/-210 vs 485+/-264 kcal per day). CONCLUSION: Adherence
to the behavioral intervention was similar in AA and Caucasian women. However,
neglecting to account for the lower energy requirements in AA women when
calculating the energy prescription resulted in a lower level of calorie
restriction and, hence, less body weight loss. Therefore, to achieve similar
weight loss in AA women, the prescribed caloric restriction cannot be based on
weight alone, but must be lower than in Caucasians, to account for lower energy
requirements.
PMID- 24352293
TI - Calcium-dependent release of adipocyte fatty acid binding protein from human
adipocytes.
AB - BACKGROUND: Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic
protein of the adipocytes, but also abundantly present in human plasma; its
plasma concentrations were linked to obesity and metabolic syndrome. Recent
studies have suggested a direct extracellular effect of FABP4 in the regulation
of glucose metabolism and heart function independently of its effect as a carrier
protein. Interestingly, FABP4 has no secretory signal sequence; hence, the
mechanisms how FABP4 is released from adipocytes are unclear. METHODS AND
RESULTS: In this study we investigated the mechanisms for FABP4 secretion from
human adipocytes by using isolated primary pre-adipocytes (PAs) and the human
adipocyte cell strain Simpson-Golabi-Behmel syndrome. In undifferentiated PAs,
FABP4 expression was barely detectable and increased continuously during
differentiation. The increase in FABP4 mRNA expression was accompanied by high
levels of FABP4 secretion. In differentiated human adipocytes, FABP4 secretion
was not abolished by blocking the Golgi-dependent secretory pathway in vitro,
supporting a non-classical secretion mechanism for FABP4. However, raising
intracellular Ca(2+) levels enhanced FABP4 secretion in a concentration-dependent
manner. CONCLUSION: This study shows that FABP4 is actively released from human
adipocytes in vitro via a non-classical, calcium-dependent mechanism.
PMID- 24352294
TI - Postprandial thermogenesis and substrate oxidation are unaffected by sleep
restriction.
AB - BACKGROUND/OBJECTIVES: The extent to which alterations in energy expenditure (EE)
in response to sleep restriction contribute to the short sleep-obesity
relationship is not clearly defined. Short sleep may induce changes in resting
metabolic rate (RMR), thermic effect of food (TEF) and postprandial substrate
oxidation. SUBJECTS/METHODS: Ten females (age and body mass index: 22-43 years
and 23.4-28 kg m(-2)) completed a randomized, crossover study assessing the
effects of short (4 h per night) and habitual (8 h per night) sleep duration on
fasting and postprandial RMR and respiratory quotient (RQ). Measurements were
taken after three nights using whole-room indirect calorimetry. The TEF was
assessed over a 6-h period following consumption of a high-fat liquid meal.
RESULTS: Short versus habitual sleep did not affect RMR (1.01+/-0.05 and 0.97+/
0.04 kcal min(-1); P=0.23). Fasting RQ was significantly lower after short versus
habitual sleep (0.84+/-0.01 and 0.88+/-0.01; P=0.028). Postprandial EE (short:
1.13+/-0.04 and habitual: 1.10+/-0.04, P=0.09) and RQ (short: 0.88+/-0.01 and
habitual: 0.88+/-0.01, P=0.50) after the high-fat meal were not different between
conditions. TEF was similar between conditions (0.24+/-0.02 kcal min(-1) in both;
P=0.98), as was the ~6-h incremental area under the curve (1.16+/-0.10 and 1.17+/
0.09 kcal min(-1) * 356 min after short and habitual sleep, respectively;
P=0.92). CONCLUSIONS: Current findings observed in non-obese healthy
premenopausal women do not support the hypothesis that alterations in TEF and
postprandial substrate oxidation are major contributors to the higher rate of
obesity observed in short sleepers. In exploring a role of sleep duration on EE,
research should focus on potential alterations in physical activity to explain
the increased obesity risk in short sleepers.
PMID- 24352295
TI - Livedoid vasculopathy: clinical features and treatment in 24 Chinese patients.
AB - Livedo vasculopathy (LV) is a chronic cutaneous disorder characterised by
recurrent, painful ulceration ending in stellate scars. We have conducted a
retrospective study of clinical features and treatment response of LV in 24
Chinese patients. LV occurred more frequently in women (male:female ratio 1:3).
The peak age at onset of disease ranged from 14 to 20 years, younger than
previously published data. 87.5% of the patients (21/24) showed significant
summer exacerbation with ulcer formation. Out of 24 patients tested, 14 (58.3%)
had positive antiphospholipid antibodies. Ten out of 14 patients (71.4%) were
tested to be hypersensitive to multivalent insect antigens. Combinative anti
inflammatory therapy with steroids, tetracycline and Tripterygium glycosides plus
antiplatelet/profibrinolytic drugs promoted quick healing of ulcer and reduce
recurrence. The younger age of disease presentation and significant summer
exacerbation are 2 novel clinical features observed in this study. These findings
suggest that apart from procoagulation other risk factors may contribute
significantly to the pathogenesis of LV. Although antiplatelet/profibrinolytic
drugs are deemed as a first line therapy for LV, anti-inflammatory medications
such as steroids, tetracycline and Tripterygium glycosides, from our experiences,
are indispensable, especially for acute, ulcerative stage of disease.
PMID- 24352296
TI - Fructophilic characteristics of Fructobacillus spp. may be due to the absence of
an alcohol/acetaldehyde dehydrogenase gene (adhE).
AB - Fructophilic strains of Leuconostoc spp. have recently been reclassified to a new
genus, i.e., Fructobacillus. Members of the genus are differentiated from
Leuconostoc spp. by their preference for fructose on growth, requirement of an
electron acceptor for glucose metabolism, and the inability to produce ethanol
from the fermentation of glucose. In the present study, enzyme activities and
genes involved in ethanol production were studied, since this is the key pathway
for NAD(+)/NADH cycling in heterofermentative lactic acid bacteria.
Fructobacillus spp. has a weak alcohol dehydrogenase activity and has no
acetaldehyde dehydrogenase activity, whereas both enzymes are active in
Leuconostoc mesenteroides. The bifunctional alcohol/acetaldehyde dehydrogenase
gene, adhE, was described in Leuconostoc spp., but not in Fructobacillus spp.
These results suggested that, due to the deficiency of the adhE gene, the normal
pathway for ethanol production is absent in Fructobacillus spp. This leads to a
shortage of NAD(+), and the requirement for an electron acceptor in glucose
metabolism. Fructophilic characteristics, as observed for Fructobacillus spp.,
are thus due to the absence of the adhE gene, and a phenotype that most likely
evolved as a result of regressive evolution.
PMID- 24352297
TI - Development of SCAR markers to determine the mating types of Lepista nuda
protoplast monokaryons.
AB - Lepista nuda (Bull. ex Fr.) Cooke belongs to Tricholomataceae and is an edible
fungus with both economic and medical value. Mycelia were isolated from the
fruiting bodies of L. nuda and were used to prepare the protoplast monokaryons.
One hundred and fifteen monokaryons were obtained and their mating types were
determined using somatic incompatibility tests. Protoplast monokaryons segregated
into either the A1B1 or the A2B2 mating types. Inter-simple sequence repeats and
sequence-related amplified polymorphism fingerprinting were used to analyse the
mating types of these protoplast monokaryons and 16 sequence-characterised
amplified region primers were developed to efficiently differentiate between the
monokaryon mating types. Multiplex PCR analyses were also established. The data
presented here outline a method for the precise and rapid identification of
protoplast monokaryon mating types, which has the promise to shorten the period
required for conventional crossbreeding.
PMID- 24352298
TI - Mediatorless N(2) incorporated diamond nanowire electrode for selective detection
of NADH at stable low oxidation potential.
AB - The electrocatalytic properties of a N2 incorporated diamond nanowire (N-DNW)
unmodified electrode towards the oxidation of nicotinamide adenine dinucleotide
(NADH) was critically evaluated. The electrochemical behavior of the N-DNW
unmodified electrode was examined and compared with that of boron-doped diamond,
glassy carbon electrode, and graphite electrodes. The N-DNW electrode had high
selectivity and high sensitivity for the differential pulse voltammetric
detection of NADH in the presence of ascorbic acid at the lower and stable
oxidation potential. Moreover, it exhibited strong stability after prolonged
usage. The oxidation peak potential at the N-DNW electrode remained unchanged
even after exposure to the solution, followed by washing, drying, and storage in
laboratory air for 20 days, with minimization of surface contamination.
Therefore, the N-DNW unmodified electrode shows promise for the detection of NADH
and is attractive for use in a dehydrogenase based biosensor and other analytical
applications.
PMID- 24352299
TI - Separation of rare earths from transition metals by liquid-liquid extraction from
a molten salt hydrate to an ionic liquid phase.
AB - The solvent extraction of trivalent rare-earth ions and their separation from
divalent transition metal ions using molten salt hydrates as the feed phase and
an undiluted fluorine-free ionic liquid as the extracting phase were investigated
in detail. The extractant was tricaprylmethylammonium nitrate, [A336][NO3], and
the hydrated melt was calcium nitrate tetrahydrate, Ca(NO3)2.4H2O. The extraction
behavior of rare-earth ions was studied for solutions of individual elements, as
well as for mixtures of rare earths in the hydrated melt. The influence of
different extraction parameters was investigated: the initial metal loading in
the feed phase, percentage of water in the feed solution, equilibration time, and
the type of hydrated melt. The extraction of rare earths from Ca(NO3)2.4H2O was
compared with extraction from CaCl2.4H2O by [A336][Cl] (Aliquat 336). The nitrate
system was found to be the better one. The extraction and separation of rare
earths from the transition metals nickel, cobalt and zinc were also investigated.
Remarkably high separation factors of rare-earth ions over transition metal ions
were observed for extraction from Ca(NO3)2.4H2O by the [A336][NO3] extracting
phase. Furthermore, rare-earth ions could be separated efficiently from
transition metal ions, even in melts with very high concentrations of transition
metal ions. Rare-earth oxides could be directly dissolved in the Ca(NO3)2.4H2O
phase in the presence of small amounts of Al(NO3)3.9H2O or concentrated nitric
acid. The efficiency of extraction after dissolving the rare-earth oxides in the
hydrated nitrate melt was identical to extraction from solutions with rare-earth
nitrates dissolved in the molten phase. The stripping of the rare-earth ions from
the loaded ionic liquid phase and the reuse of the recycled ionic liquid were
also investigated in detail.
PMID- 24352300
TI - Do people desire to be healthier than other people? A short note on positional
concerns for health.
AB - Contrary to traditional economic postulates, people do not only care about their
absolute position but also about their relative position. However, empirical
evidence on positional concerns in the context of health is scarce, despite its
relevance for health care policy. This paper presents a first explorative study
on positional concerns in the context of health. Using a 'two-world' survey
method, a convenience sample of 143 people chose between two options (having more
in absolute terms or having more in relative terms) in several health and non
health domains. Our results for the non-health domains compare reasonably well to
previous studies, with 22-47% of respondents preferring the positional option. In
the health domain, these percentages were significantly lower, indicating a
stronger focus on absolute positions. The finding that positional concerns are
less prominent in the health domain has important implications for health policy,
for instance in balancing reduction of socio-economic inequalities and absolute
health improvements.
PMID- 24352301
TI - Erythematous nodule of the left eyebrow in a 14-year-old boy.
PMID- 24352302
TI - Analysis and identification of bite marks in forensic casework.
AB - Analysis of bite marks plays an important role in personal identification in
forensic casework. Bite marks can be recorded in violent crimes such as sexual
offences, homicides, child abuse cases, and during sports events. The
arrangement, size and alignment of human teeth are individualistic to each
person. Teeth, acting as tools leave recognizable marks depending on tooth
arrangement, malocclusion, habits, occupation, tooth fracture, and missing or
extra teeth. Bite mark identification is based on the individuality of a
dentition, which is used to match a bite mark to a suspect. Bite marks are often
considered as valuable alternative to fingerprinting and DNA identification in
forensic examinations. The present review describes the classification,
characteristics, mechanism of production, and appearance of bite mark injuries,
collection of evidence, comparison techniques, and technical aids in the analysis
of the bite marks.
PMID- 24352303
TI - Prevalence based epidemiological cancer statistics: a brief assessment from
different populations in India.
AB - Modern civilization, urbanization, industrialization, changes in daily life,
population growth and ageing all have contributed to epidemiological changes in
many diseases, including cancer, in India and other countries. Tobacco has been
identified as the most important cause of cancer followed by alcohol consumption,
dietary practices, inadequate physical activity, infections due to viruses and
sexual behavior. The total number of new cancer cases is increasing rapidly, due
to growth in size of the population, and an increase in the proportion of elderly
persons, as a result of improved life expectancy, following control of
communicable diseases. Such changes in the age structure automatically alter the
disease pattern associated with ageing and increase the burden of problems such
as cancer, cardiovascular and other non-communicable diseases in the society.
Knowledge based on epidemiological patterns and trends would be of great help in
identifying persons at high risk for the development of a particular cancer.
Public education on 'tobacco and its health hazards', recommended dietary
guidelines, safe sexual practices, and lifestyle modifications form the
scientific basis for planning and organizing prevention, diagnosis and treatment
of cancer in a community. Moreover, incorporating screening for cervical, breast
and oral cancers into the peripheral health infrastructure can have a significant
effect on reducing mortality from these diseases. This paper highlights the
incidence and prevalence based epidemiological cancer statistics, its early
detection and prevention measures in India.
PMID- 24352304
TI - Teledentistry: knowledge and attitudes among dentists in Udaipur, India.
AB - BACKGROUND: Teledentistry is a synergistic combination of telecommunications
technology; internet and dental practice which shows promising potential to be a
highly effective mechanism for enhancing diagnosis and related treatment. AIM: To
assess the knowledge and attitudes regarding teledentistry among dentists of
Udaipur. METHODS: A cross-sectional survey was conducted among the total of 105
dentists in Udaipur, India. A self administered structured questionnaire was used
to assess their knowledge (8 items) and attitude (12 items) regarding
teledentistry. The response format was based on 5-point Likert scale. Analysis of
variance, t-test and multiple linear regression model was utilized for
statistical analysis. Level of significance was fixed at p <= 0.05. RESULT: The
mean scores for knowledge and attitudes were 25.61 +/- 3.197 and 38.61 +/- 4.742
respectively. Bivariate analysis revealed that work experience was significantly
associated with both knowledge and attitude means scores (p <= 0.05). Significant
predictors of knowledge scores were work experience (R=0.381, p=0.000),
qualification (R=0.504, p=0.000), internet access (R=0.548, p=0.000); for
attitude scores it was only internet access (R=0.261, p=0.007). CONCLUSION: An
unbalanced knowledge of teledentistry among current dentists has suggested the
need for awareness programmes to fill the knowledge gaps and instill positive
attitudes.
PMID- 24352305
TI - Comparative evaluation of bactericidal effects on Enterococcus faecalis using
diode laser irradiation, sodium hypochlorite and chlorhexidine gluconate
irrigation"- an in vitro study.
AB - AIM: This in vitro study was performed to evaluate the bactericidal effects of
Diode laser, 3% Sodium hypochlorite and 2% Chlorhexidine gluconate irrigation on
root canals infected with Enterococcus faecalis. METHOD: Seventy single rooted
central incisors were prepared and sixty was contaminated with Enterococcus
faecalis. After 48 hours of incubation samples were divided into 7 groups-Group 1
Sterility control (canals not contaminated with Enterococcus faecalis ); Group 2
Positive control canals with no other treatment; Group 3- canals were treated
with 3% NaOCl during biomechanical preparation; Group 4- canals were treated with
2% CHX; Group 5- canals were treated with 980nm diode laser; Group 6- was treated
with combination of laser and 3% NaOCl; Group 7- were treated with laser and 2%
CHX, the CFU of all the groups were checked. RESULT: Group 3 and 6 were
significantly effective as there was no growth of E. faecalis (p=<0.001), group 7
was significantly more effective than group 2 (p=<0.001). There was no
statistical significance between group 7 and group 3 and 6 (p=0. 474), the
maximum amount of growth was seen in group 4. CONCLUSION: 3% NaOCl was the most
effective irritant comparatively and combination of 2% CHX and laser was as
effective as 3% NaOCl and hence can be used as an alternative for 3% NaOCl.
PMID- 24352306
TI - A pilot study into the effect of whisky, wine and beer consumption on tooth
surface dissolution.
AB - AIM: To assess the potential of acute alcohol consumption to dissolve tooth
surfaces and to evaluate the difference in the dissolution potential of whisky,
beer and wine. METHODS: The study sample comprised 36 healthy male volunteers
with mean age of 26.27 (SD-1.96) years (range 25-30 years). The study design
involved randomly allocating the 36 individuals into three groups of alcohol
consumption (whisky, beer, wine) with 12 subjects in each group. Two samples of
paraffin stimulated whole saliva were collected, at baseline and immediately
after consumption of alcohol. Saliva was subjected to chemical analysis for pH,
ionic calcium and inorganic phosphate. RESULTS: There was a significant
difference for mean change in salivary pH, calcium and inorganic phosphate
between the three alcohol groups. A significant reduction in the mean pH was
observed after consumption of any form of alcoholic drink (mean change=-1.34,
p=0.0001). Beer consumers had highest reduction in mean pH (1.75) followed by the
wine (1.13) and whisky consumers (1.12) (p=0.045 and p=0.087 respectively). Mean
calcium (mean change=5.75, p=0.0001) and inorganic phosphate (mean change=8.42,
p=0.003) concentration significantly increased in the whole study sample. Mean
inorganic phosphate and calcium concentrations increased after consumption of
whisky and wine while a drop in their concentrations was observed in beer
consumers. CONCLUSIONS: Salivary pH decreased significantly in subjects belonging
to all the three groups. In both whisky and wine groups, there was a rise in
salivary inorganic phosphate concentration while only whisky was able to dissolve
calcium from the tooth surfaces.
PMID- 24352307
TI - Qualitative and quantitative comparative evaluation of sealing ability of
guttaflow, thermoplasticized gutta percha and lateral compaction for root canal
obturation: a cohort, controlled, ex-vivo study.
AB - AIMS: To compare and evaluate the apical sealing ability of Guttaflow,
Thermoplasticized Gutta percha and Lateral Compaction technique using dye
penetration method, Robertson's clearing technique and triocular
stereomicroscopy. METHODS: A total of eighty extracted human mandibular molars
were decoronated, sectioned and instrumented with rotary protapers size F1. Teeth
were randomly divided into three experimental groups of 20 each labeled as Group
G1 (Guttaflow), G2 (E&Q plus - mechanized thermoplasticized gutta-percha), and G3
(laterally compacted gutta percha). Group G4 containing 20 teeth served as
positive control. All the teeth were given two coats of nail varnish leaving 2 mm
at the apex. Teeth were immersed in India ink for 48 hrs, demineralized and
cleared (rendered translucent) with methyl salicylate using Robertson's
technique. The apical dye penetration was examined using a triocular
stereomicroscope. RESULTS: The mean dye penetration was recorded to be maximum
for E&Q Plus i.e. 0.69 mm whereas the mean dye penetration value for all canals
obturated with Guttaflow was found to be minimum i.e. 0.35 mm which was
comparable to that of Lateral compaction technique i.e. 0.36. On statistical
analysis (T variance and ANOVA tests), no statistical significant differences
were revealed in terms of sealing ability of different obturating materials.
CONCLUSION: Guttaflow exhibited an acceptable sealing ability, better than
thermoplasticized gutta-percha, and comparable to lateral compaction, though the
mean comparative leakage scores were found to be statistically insignificant.
PMID- 24352308
TI - Oral health care provision systems in the Black Sea countries: part 15 Georgia.
AB - This paper describes how oral health care delivery is organized in the country of
Georgia in 2013. It also describes the dental workforce, detailing the number of
dentists in dental specialties. A section on dental education both at
undergraduate as well as post-graduate levels follows. National statistics and
governmental reports were used as data sources for this paper. They were provided
by the Ministry of Health and Public Service Hall (Ministry of Justice of
Georgia).
PMID- 24352309
TI - Lead dentists in the public dental service in Finland during a major reform.
AB - BACKGROUND: A major reform of dental care was conducted in Finland in 2001-2002.
As a result, care from the Public Dental Service (PDS) was for first time made
available to adults born before 1956 and the reimbursement of basic dental care
in the private sector by the National Insurance Institution was extended to cover
all adult age groups. AIM: To survey how the position and role of the lead
dentists in the PDS and their leadership role had changed during the eight years
since the reform was introduced. METHODS: Data on leadership qualities and styles
and proceedings of the implementation process of the reform were collected from
the lead PDS dentists (n=161) in 2011 using an e-mailed questionnaire.
Comparisons were made with a previous study performed in 2003. The response rates
were the same, 73%, in both years. Factor analysis, chi-square and non parametric
tests were used in analysis. RESULTS: The number of lead dentists had fallen by
39% as the sizes of the PDS units had increased. Only a third (30%) had applied
for the leadership position and 17% were full-time lead dentists (usually in
units having 40,000 or more inhabitants). Although most respondents (72%) felt
that they were good goal-oriented managers, and almost all (94%) that they were
good people-oriented leaders, they felt that a lead dentist's position in the
municipal hierarchy had become weaker although the PDS after the reform had much
larger population responsibility locally. Most lead dentists, 72%, claimed that
they had been forced to work with insufficient staff in relation to the increased
demand for care, especially lack of dentists. CONCLUSIONS: Being a lead dentist
in the PDS continued to be a rather lonely task and attracted male dentists more
than female dentists. Over the years the lead dentists' self-confidence in their
leadership role had improved but their independent decision-making power had
decreased and their position in municipal decision making had stayed weak. Those
who had applied for the leading post themselves worked in larger PDS units and
had enough leadership education and were most satisfied with their work.
PMID- 24352310
TI - Preliminary ex-vivo and an animal model evaluation of Ocimum sanctum's essential
oil extract for its antibacterial and anti- inflammatory properties.
AB - AIM: To evaluate the essential oil extract of the au Ocimum sanctum for its
antibacterial and anti inflammatory efficacy. METHODS: The essential oil extract
was prepared in the Clevenger's apparatus. Antibacterial efficacy was tested
against Enterococcus faecalis at two concentrations i.e. 100 & 50%. Bacterial
growth was measured spectrophotometrically and percentage inhibition was
calculated. Anti- inflammatory efficacy was tested on an established adult albino
rat model. Autoclaved cotton pellets were used for inducing the chronic
inflammatory conditions for 7 days. On day 8, the cotton pellets induced
granuloma were excised, dried and weighed. The percentage inhibition of the
granuloma was calculated. RESULTS: The essential oil extract of Ocimum sanctum
showed antibacterial efficacy, which improved with an increase in concentration
and contact period. It also had a significant (p=0.034) anti- inflammatory
action. CONCLUSION: This ex-vivo and an animal model study documented the
antibacterial and anti- inflammatory properties of the essential oil extract of
Ocimum sanctum, for its proposed use as an intracanal medicament.
PMID- 24352311
TI - Distinction of Mohr's syndrome from OFD type I: case report and review of the
literature.
AB - The Oralfacialdigital Syndromes (OFD) results from the pleiotropic effect of a
morphogenetic impairment affecting almost invariably the mouth, face and digits.
In view of the different modes of inheritance and the different prognoses of the
most common OFDs; OFD I, and II, it is important to establish a correct diagnosis
in these patients. A case of type II OFD syndrome is being reported and the
distinguishing clinico-radiological features with type I are compared. This case
reports also reviews the various other types of OFD and their distinguishing
characteristics and emphasizes the early diagnosis and treatment of the same.
PMID- 24352312
TI - Analgesic effect of etoricoxib compared to ibuprofen on post endodontic pain.
AB - AIMS: Etoricoxib is a second-generation selective COX-2 inhibitor. There are a
few researches investigating analgesic effect of Etoricoxib in dentistry.
METHODS: This randomized, double-blind, active-control study included sixty
patients with clinical pulpal diagnosis of necrosis of the first mandibular molar
and an associated periapical radiolucency who experienced severe pain (more than
60 out of 100 in scale of Visual Analog Scale (VAS). The patients were equally
randomized into four groups, who received 60 mg etoricoxib (group 1), 90 mg
etoricoxib (group 2), 120 mg etoricoxib (group 3), and 400 mg ibuprofen (group
4). All patients randomly received a single dose of the drug after the first
session of the root canal therapy. Using VAS, the severity of pain was recorded
2, 4, 6, 12, 24, 48, and 72 hours after the drug was administered. RESULTS:
Changing trends of pain over the time was significant for all groups (P=0.003).
In addition, there was not a significant difference between various study arms
(P=0.146). CONCLUSION: The results showed that ibuprofen had a comparable effect
with various dosage of etoricoxib and may remain as the choice analgesic for
dental pulpal pain.
PMID- 24352315
TI - Universal influenza virus vaccines: need for clinical trials.
PMID- 24352316
TI - Outflanking HCV.
PMID- 24352317
TI - A new VEGF connection between two old neighbors.
PMID- 24352318
TI - Neutrophil recruitment: perivascular macrophages 'duke it out' with
Staphylococcus aureus.
PMID- 24352319
TI - Innate TCRs: single use only.
PMID- 24352332
TI - Aneurysmal degeneration of deep lower extremity vein conduits used for vascular
reconstruction.
AB - BACKGROUND: Successful outcomes have been reported with the use of
femoropopliteal vein (FPV) grafts as arterial conduits. We identified 2 patients
with a rare complication, true, nonanastomotic aneurysmal degeneration. METHODS:
Patients from 1997 through 2009 that utilized FPV grafts for revascularization
were analyzed. We contacted survivors by phone and conducted a literature search
of FPV aneurysms. RESULTS: Of the total of 14 patients in our practice whose FPV
was used as a conduit during the study period, 2 developed nonanastomotic FPV
graft aneurysms. The mean follow-up time was 33.44 months. Literature review
uncovered only 1 previously published case of FPV aneurysmal degeneration.
CONCLUSIONS: Our experience suggests that nonanastomotic aneurysms of FPV grafts
may occur more often than those suspected previously. Our study represents the
first reports of aneurysmal degeneration affecting FPV grafts when used for
vascular reconstructions.
PMID- 24352326
TI - NF-kappaB control of T cell development.
AB - The NF-kappaB signal transduction pathway is best known as a major regulator of
innate and adaptive immune responses, yet there is a growing appreciation of its
importance in immune cell development, particularly of T lineage cells. In this
Review, we discuss how the temporal regulation of NF-kappaB controls the stepwise
differentiation and antigen-dependent selection of conventional and specialized
subsets of T cells in response to T cell receptor and costimulatory, cytokine and
growth factor signals.
PMID- 24352333
TI - Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein
kinase C in guinea pig urinary bladder smooth muscle.
AB - Large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels are critical
regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC
modulates the contraction of DSM and BK channel activity in non-DSM cells;
however, the cellular mechanism regulating the PKC-BK channel interaction in DSM
remains unknown. We provide a novel mechanistic insight into BK channel
regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca(2+)
imaging, and functional studies of DSM contractility to elucidate BK channel
regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed
that pharmacological activation of PKC with PMA inhibited the spontaneous
transient BK currents in native freshly isolated guinea pig DSM cells. Current
clamp recordings revealed that PMA significantly depolarized DSM membrane
potential and inhibited the spontaneous transient hyperpolarizations in DSM
cells. The PMA inhibitory effects on DSM membrane potential were completely
abolished by the selective BK channel inhibitor paxilline. Activation of PKC with
PMA did not affect the amplitude of the voltage-step-induced whole cell steady
state BK current or the single BK channel open probability (recorded in cell
attached mode) upon inhibition of all major Ca(2+) sources for BK channel
activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA
elevated intracellular Ca(2+) levels in DSM cells and increased spontaneous
phasic and nerve-evoked contractions of DSM isolated strips. Our results support
the concept that PKC activation leads to a reduction of BK channel activity in
DSM via a Ca(2+)-dependent mechanism, thus increasing DSM contractility.
PMID- 24352334
TI - Detection of differentially regulated subsarcolemmal calcium signals activated by
vasoactive agonists in rat pulmonary artery smooth muscle cells.
AB - Intracellular calcium (Ca(2+)) plays pivotal roles in distinct cellular functions
through global and local signaling in various subcellular compartments, and
subcellular Ca(2+) signal is the key factor for independent regulation of
different cellular functions. In vascular smooth muscle cells, subsarcolemmal
Ca(2+) is an important regulator of excitation-contraction coupling, and
nucleoplasmic Ca(2+) is crucial for excitation-transcription coupling. However,
information on Ca(2+) signals in these subcellular compartments is limited. To
study the regulation of the subcellular Ca(2+) signals, genetically encoded
Ca(2+) indicators (cameleon), D3cpv, targeting the plasma membrane (PM),
cytoplasm, and nucleoplasm were transfected into rat pulmonary arterial smooth
muscle cells (PASMCs) and Ca(2+) signals were monitored using laser scanning
confocal microscopy. In situ calibration showed that the Kd for Ca(2+) of D3cpv
was comparable in the cytoplasm and nucleoplasm, but it was slightly higher in
the PM. Stimulation of digitonin-permeabilized cells with 1,4,5-trisphosphate
(IP3) elicited a transient elevation of Ca(2+) concentration with similar
amplitude and kinetics in the nucleoplasm and cytoplasm. Activation of G protein
coupled receptors by endothelin-1 and angiotensin II preferentially elevated the
subsarcolemmal Ca(2+) signal with higher amplitude in the PM region than the
nucleoplasm and cytoplasm. In contrast, the receptor tyrosine kinase activator,
platelet-derived growth factor, elicited Ca(2+) signals with similar amplitudes
in all three regions, except that the rise-time and decay-time were slightly
slower in the PM region. These data clearly revealed compartmentalization of
Ca(2+) signals in the subsarcolemmal regions and provide the basis for further
investigations of differential regulation of subcellular Ca(2+) signals in
PASMCs.
PMID- 24352337
TI - Biologic therapies and pregnancy: the story so far.
AB - Biologic therapies have revolutionized treatment outcomes for patients with
inflammatory arthritis. However, there remains a concern regarding their safety
during conception, pregnancy and breastfeeding. Data on the safety of these
treatments are largely limited to uncontrolled case reports. Collective evidence
from many hundreds of pregnancies in inflammatory arthritis and IBD have
suggested that exposure to anti-TNF therapies at the time of conception or during
the first trimester does not result in an increased risk of adverse pregnancy and
fetal outcomes. Monoclonal antibodies, and to a lesser extent recombinant fusion
proteins, do cross the placenta during the second and third trimester and are
functional in the fetus, as evidence by lymphopaenia reported at birth in
children exposed to rituximab in utero. In addition, live vaccines should be
avoided in children with in utero exposure to biologics for at least the first 6
months of life. The longer-term effects of in utero exposure remain unknown.
Studies suggest that many of these drugs do enter breast milk in small amounts,
but the extent to which they are absorbed by the infant is less clear. Limited
reports have not suggested adverse pregnancy outcomes in women whose partners
were exposed to anti-TNF therapies or rituximab at the time of conception. Data
on other biologic therapies, including anakinra, abatacept and tocilizumab, in
both men and women remain extremely limited.
PMID- 24352338
TI - Is radiographic progression of late-onset rheumatoid arthritis different from
young-onset rheumatoid arthritis? Results from the Swiss prospective
observational cohort.
AB - OBJECTIVE: RA can be categorized into late-onset RA (LORA, >60-65 years) and
young-onset RA (YORA, 30-55 years), depending on the patient's age at disease
onset. Since the average age of the population is continuously increasing, LORA
will most probably gain in importance in the future. Despite this growing
importance, LORA has not been the focus of much interest in the past. The aim of
this study was to analyse radiographic damage progression of early disease in
LORA compared with YORA patients. METHODS: We included all patients from the
Swiss RA registry, Swiss Clinical Quality Management in RA, with recent-onset
arthritis, either RA (disease duration <=1 year) or undifferentiated arthritis,
as diagnosed by the data-entering physician. Patients were followed for 5 years.
The cut-off between YORA and LORA was operationally set at 60 years of age. The
primary outcome of this study was disease progression and activity, which was
assessed based on the 28-joint DAS (DAS28) and the progression of joint erosions
using a validated scoring system (Ratingen score). RESULTS: A total of 592
patients with early disease were analysed. The age at disease onset had a
Gaussian distribution, with a single peak at 54 years of age; 366 patients were
categorized as YORA and 226 as LORA at disease onset. DAS28 scores were
significantly higher among LORA as compared with YORA patients (4.8 vs 4.5, P =
0.049). Corticosteroids were used in 68% of LORA patients as a first-line
treatment, compared with 25.4% in YORA patients (chi(2) test: 54.58; P < 0.0001).
In contrast, DMARDs were used in 100% of the YORA patients as first-line
treatment, compared with 91.2% of the LORA patients. During follow-up, new
glucocorticoids, synthetic DMARDs or biologic DMARDs were initiated in 32.8%,
61.1% and 14.1% of all YORA patients and 17.5%, 54.6% and 6.6% of LORA patients,
respectively (chi(2) test: 7.08, 22.53, 54.4; all P < 0.01). The DAS28 scores
decreased in both groups during the observed time period, and the initial
differences in disease activity vanished after 6 months and during the subsequent
follow-up. The Ratingen score was higher in LORA than in YORA patients at
inclusion (12.7 vs 5.6, P < 0.0001). The rate of radiographic progression at 5
years was similar when comparing LORA and YORA (3.3 vs 2.6, respectively, P =
0.64). The Ratingen scores at onset and during follow-up over 5 years did not
clearly separate LORA and YORA into two groups, but rather, increased linearly
when comparing the patients in groups per decade from 20 to 92 years of age.
CONCLUSION: Our results did not show LORA as a separate subgroup of RA with a
different prognosis with regard to radiographic progression.
PMID- 24352336
TI - Noxa in rheumatic diseases: present understanding and future impact.
AB - Impaired programmed cell death is an important contributing mechanism in the
development of chronic inflammatory and autoimmune diseases. Overexpression of
Bcl-2 family proteins in such diseases has led to the concept of targeted
suppression of these proteins as a primary therapeutic strategy. However, limited
success with this approach has prompted pharmacologists to look at the other side
of the coin, with the aim of reactivating jeopardized pro-apoptotic proteins that
may neutralize Bcl-2 or other anti-apoptotic molecules. In this effort, BH3-only
proteins have gained recent attention as endogenous molecules for the
sensitization of resistant cells to undergo apoptosis. Among the BH3-only family,
Noxa stands out as exceptional for its specificity to bind Mcl-1 and Bcl-2 and
blunt their biological properties. Noxa is now being tested as a promising
therapeutic target in cancer biology. Nonetheless, its role and clinical
application still lack validation in autoimmune diseases, including rheumatic
conditions. This is partly attributed to the significant gap in our understanding
of its regulatory role and how either overexpression of Noxa or delivery of BH3
mimetics could be therapeutically exploited. In this review we highlight some
recent studies in RA, OA, SLE and SS suggesting that Noxa may be used as a
potential therapeutic target to circumvent invasive and tissue destructive
processes in these rheumatic diseases.
PMID- 24352335
TI - Cellular mechanisms of tissue fibrosis. 6. Purinergic signaling and response in
fibroblasts and tissue fibrosis.
AB - Tissue fibrosis occurs as a result of the dysregulation of extracellular matrix
(ECM) synthesis. Tissue fibroblasts, resident cells responsible for the synthesis
and turnover of ECM, are regulated via numerous hormonal and mechanical signals.
The release of intracellular nucleotides and their resultant autocrine/paracrine
signaling have been shown to play key roles in the homeostatic maintenance of
tissue remodeling and in fibrotic response post-injury. Extracellular nucleotides
signal through P2 nucleotide and P1 adenosine receptors to activate signaling
networks that regulate the proliferation and activity of fibroblasts, which, in
turn, influence tissue structure and pathologic remodeling. An important
component in the signaling and functional responses of fibroblasts to
extracellular ATP and adenosine is the expression and activity of
ectonucleotideases that attenuate nucleotide-mediated signaling, and thereby
integrate P2 receptor- and subsequent adenosine receptor-initiated responses.
Results of studies of the mechanisms of cellular nucleotide release and the
effects of this autocrine/paracrine signaling axis on fibroblast-to-myofibroblast
conversion and the fibrotic phenotype have advanced understanding of tissue
remodeling and fibrosis. This review summarizes recent findings related to
purinergic signaling in the regulation of fibroblasts and the development of
tissue fibrosis in the heart, lungs, liver, and kidney.
PMID- 24352339
TI - Efficacy and safety of canakinumab therapy in paediatric patients with cryopyrin
associated periodic syndrome: a single-centre, real-world experience.
AB - OBJECTIVE: The aim of this study was to determine the short- and long-term
efficacy and safety of 8-weekly canakinumab therapy in children with cryopyrin
associated periodic syndromes (CAPS) in routine clinical practice. METHODS: A
single-centre observational study was performed. Patients were assessed every 8
weeks at a dedicated clinic. Standardized assessments were the 10-domains DAS for
CAPS, acute phase reactants (APRs), physician's global assessment of disease
activity, Child Health Assessment Questionnaire (CHAQ) and Child Health
Questionnaire Parent Form 28 (CHQPF-28). The primary endpoint was clinical
improvement, defined as a reduction of DAS score 8 weeks after commencing
therapy. Secondary endpoints included sustained clinical improvement in APRs,
relapses, CHAQ score and CHQPF-28 score. RESULTS: Ten children with CAPS [eight
Muckle-Wells syndrome (MWS), two chronic infantile cutaneous neurological
articular (CINCA); median age 6.3 years] received 8-weekly canakinumab treatments
at 2-8.7 mg/kg for a median of 21 months (range 12-31 months). Nine of 10
patients improved after the first dose: baseline median DAS of 7.5/20 decreased
to 3.5/20 at 8 weeks (P = 0.04). This clinical improvement was sustained at a
median follow-up of 21 months (range 12-31 months). Children with CINCA required
higher doses of canakinumab than those with MWS. CHAQ and CHQ scores indicated
improvement in functioning and health-related quality of life (HRQoL). Treatment
was well tolerated, with no injection site reactions and no serious infections.
CONCLUSION: Canakinumab, although costly, is a safe and effective treatment for
CAPS in children, leading to sustained improvement in disease activity,
serological markers, functional ability and HRQoL.
PMID- 24352340
TI - Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary
Raynaud's phenomenon: a double-blind, randomized, cross-over study.
AB - OBJECTIVE: RP is a reversible vasoconstriction of digital arteries that causes
pain and skin discoloration. This study compared the efficacy of the new
phosphodiesterase type 5 inhibitor udenafil with that of the calcium channel
blocker amlodipine in the treatment of secondary RP. METHODS: A total of 29
patients with secondary RP associated with connective tissue diseases were
enrolled in this double-blind, randomized, cross-over study. The patients were
randomized to receive udenafil 100 mg/day or amlodipine 10 mg/day for 4 weeks.
After a washout period they were crossed over to the other drug for another 4
weeks. The primary outcome was RP frequency before and after treatment. The
secondary outcomes were RP condition scores, RP duration, number of digital
ulcers, HAQ, physician global assessment and digital artery flow before and after
treatment. RESULTS: Amlodipine and udenafil both decreased the rate of RP attack
significantly. The drugs did not differ in terms of RP frequency or any of the
secondary outcomes except for digital blood flow; udenafil improved it
significantly better than amlodipine (P = 0.021). Udenafil was well tolerated
without serious adverse effects. CONCLUSION: Udenafil and amlodipine have
comparable efficacy in improving RP attacks. In addition, udenafil improves the
blood flow in digital arteries compared with amlodipine. TRIAL REGISTRATION:
www.clinicaltrials.gov, protocol number NCT01280266.
PMID- 24352341
TI - Sitagliptin-induced bilateral Achilles tendinitis.
PMID- 24352342
TI - Photodynamic topical antimicrobial therapy for infected foot ulcers in patients
with diabetes: a randomized, double-blind, placebo-controlled study--the
D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study.
AB - This study was designed to assess the antimicrobial effect and tolerability of a
single dose of a photo-activated gel containing RLP068 in the treatment for
infected foot ulcers in subjects with diabetes. A randomized, double-blind,
parallel series, placebo-controlled phase IIa trial was performed with three
concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen
microbial load on Day 1 (before and 1 h after topical gel application and
photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to
systemic treatment with amoxicillin and clavulanic acid. Blood samples were also
drawn 1, 2, and 48 h after administration for the assessment of systemic drug
absorption. The trial was performed on 62 patients aged >=18 years, with type 1
or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a
maximum diameter <=4.6 cm. A dose-dependent reduction in total microbial load was
observed (-1.92 +/- 1.21, -2.94 +/- 1.60, and -3.00 +/- 1.82 LogCFU/ml for 0.10,
0.30, and 0.50 % RPL068 vs. -1.00 +/- 1.02 LogCFU/ml with placebo) immediately
after illumination, with a progressive fading of the effect during follow-up. No
safety issues emerged from the analysis of adverse events. Systemic absorption of
RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of
infected diabetic foot ulcers is well tolerated and produces a significant
reduction in germ load. Further clinical trials are needed to verify the efficacy
of this approach as add-on to systemic antibiotic treatment.
PMID- 24352343
TI - Impact of liver disease severity and etiology on the occurrence of diabetes
mellitus in patients with liver cirrhosis.
AB - The association between liver cirrhosis (LC) and diabetes mellitus (DM) is well
known. However, the impact of the severity or etiology of LC on the occurrence of
DM is relatively unknown. We aimed to determine the prevalence and clinical
correlates of DM in a large cohort of patients with cirrhosis. A total of 1,068
patients with LC were included in this cross sectional study (CIRCE study). The
diagnosis of cirrhosis irrespective of its etiology was based on histological
confirmation by liver biopsy or, in the absence of biopsy, on typical clinical,
morphological and biological data. Data related to the cirrhosis etiology:
alcohol, viral markers of hepatitis B, C, iron load parameters and autoimmune
markers were collected for each patient. Venous blood samples were taken in the
morning after 12-h overnight fasting. There were 383 patients with cirrhosis
associated with hepatocellular carcinoma (HCC). DM was found in 412 (39.7 %)
patients. Patients with DM were older and more likely to be overweight and male,
with a family history of DM and a diagnosis of HCC. DM was not associated with a
history of stroke or myocardial infarction. Cirrhosis secondary to hepatitis
infection was less strongly associated with DM than with NASH or alcoholic
cirrhosis. The severity of LC was not associated with DM. In multivariate
analysis, the factors associated with DM were age, BMI, a family history of DM,
and statin use. There was a significant interaction between HCC and cirrhosis
etiology for the risk of DM. Cirrhosis secondary to hepatitis was associated with
a lesser presence of DM only in patients with HCC (interaction p = 0.0015). LC
was strongly associated with DM, with around 40 % of diabetic patients. In the
group of patients with LC without HCC, diabetes was not associated with the
etiology of cirrhosis.
PMID- 24352344
TI - Pancreatitis associated with the use of GLP-1 analogs and DPP-4 inhibitors: a
case/non-case study from the French Pharmacovigilance Database.
AB - In the recent past, concerns have raised regarding the potential risk of acute
pancreatitis among type 2 diabetic patients using incretin-based drugs such as
glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4)
inhibitors. The aim of this study is to investigate the association between
exposure to incretin-based drugs and the occurrence of pancreatitis reported in
the French Pharmacovigilance Database. The case/non-case method was performed
from serious adverse drug reactions (ADRs) involving antihyperglycemic agents
(except insulin alone) reported to the French pharmacovigilance system between
March 2008 (first marketing of an incretin-based drug in France) and March 2013.
Cases were defined as reports of pancreatitis, and all other serious ADRs were
considered non-cases. Disproportionality was assessed by calculating reporting
odds ratios (ROR) adjusted for age, gender, history of pancreatitis, other
antihyperglycemic drugs and other drugs associated with a higher risk of
pancreatitis. Among 3,109 serious ADRs, 147 (4.7 %) reports of pancreatitis were
identified as cases and 2,962 reports (95.3 %) of other ADRs as non-cases. Among
the cases, 122 (83.0 %) involved incretin-based drugs. Disproportionality was
found for all incretin-based drugs (adjusted ROR: 15.7 [95 % CI 9.8-24.9]), all
GLP-1 analogs (29.4 [16.0-53.8]), exenatide (28.3 [12.8-62.3]), liraglutide (30.4
[15.4-60.0]), all DPP-4 inhibitors (12.1 [7.3-20.0]), sitagliptin (12.4 [7.3
21.0]), saxagliptin (15.1 [4.3-52.7]), and vildagliptin (7.4 [3.1-17.6]).
Temporal analysis found disproportionality for incretin-based drugs since their
first year of marketing in France. Compared with other antihyperglycemic agents,
use of incretin-based drugs is associated with an increased risk of reported
pancreatitis in France.
PMID- 24352345
TI - [Slowly enlarging space-occupying lesion of the posterior head with loss of
hair].
PMID- 24352346
TI - Formation of water-chlorophyll clusters in dilute samples of chlorophyll-a in
ether at low temperature.
AB - Simultaneously measured absorption (ABS) and magnetic circular dichroism (MCD)
spectra of the Q-bands of chlorophyll-a (Chl-a) in ether over 150-186 K reveal
that the species that forms at low temperature is a chlorophyll hydrate rather
than a diether complex. We have recently proposed a new assignment paradigm for
the spectra of chlorophillides which, for the first time, quantitatively accounts
for a wide range of observed data. Observations performed at low temperature in
ether have historically been very important for the interpretation of the spectra
of Chl-a. While our assignment for this system initially anticipated only small
spectral changes as the temperature is lowered, significant changes are known to
occur. Extensive CAM-B3LYP time-dependent density-functional theory (TD-DFT)
calculations verify that the observed spectra of the hydrated species conforms to
expectations based on our new assignment, as well as supporting the feasibility
of the proposed hydration reactions.
PMID- 24352347
TI - Genetics of inherited platelet disorders.
AB - The current review describes inherited platelet disorders, illustrates their
clinical phenotype and molecular genetic defects. Platelets are the key molecules
mediating haemostasis via adhesion, activation and clot formation at the site of
injury. The inherited platelet disorders can be classified according to their
platelet defects: receptor/cytoskeleton defects, secretion disorder, and signal
transduction defect. Patients with inherited thrombocytopathia present with
mucous membrane bleedings (epistaxis, gingival bleeding) and may present with
serious life threatening bleedings following surgery or trauma. Therefore,
biochemical and molecular genetic characterization of inherited platelet
disorders is important to understand these disorders and to support an efficient
therapy.
PMID- 24352349
TI - Neurological manifestations of influenza infection in children and adults:
results of a National British Surveillance Study.
AB - BACKGROUND: The emergence of influenza A(H1N1) 2009 was met with increased
reports of associated neurological manifestations. We aimed to describe
neurological manifestations of influenza in adults and children in the United
Kingdom that presented at this time. METHODS: A 2-year surveillance study was
undertaken through the British adult and pediatric neurological surveillance
units from February 2011. Patients were included if they met clinical case
definitions within 1 month of proven influenza infection. RESULTS: Twenty-five
cases were identified: 21 (84%) in children and 4 (16%) in adults. Six (29%)
children had preexisting neurological disorders. Polymerase chain reaction of
respiratory secretions identified influenza A in 21 (81%; 20 of which [95%] were
H1N1) and influenza B in 4 (15%). Twelve children had encephalopathy (1 with
movement disorder), 8 had encephalitis, and 1 had meningoencephalitis. Two adults
had encephalopathy with movement disorder, 1 had encephalitis, and 1 had Guillain
Barre syndrome. Seven individuals (6 children) had specific acute encephalopathy
syndromes (4 acute necrotizing encephalopathy, 1 acute infantile encephalopathy
predominantly affecting the frontal lobes, 1 hemorrhagic shock and
encephalopathy, 1 acute hemorrhagic leukoencephalopathy). Twenty (80%) required
intensive care, 17 (68%) had poor outcome, and 4 (16%) died. CONCLUSIONS: This
surveillance study described a cohort of adults and children with neurological
manifestations of influenza. The majority were due to H1N1. More children than
adults were identified; many children had specific encephalopathy syndromes with
poor outcomes. None had been vaccinated, although 8 (32%) had indications for
this. A modified classification system is proposed based on our data and the
increasing spectrum of recognized acute encephalopathy syndromes.
PMID- 24352350
TI - Reply to Munoz and Santin.
PMID- 24352351
TI - The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in
leukemic patients with neutropenia?
AB - BACKGROUND: Pulmonary mucormycosis (PM) is a life-threatening fungal infection
with an increasing incidence among patients with acute leukemia. In some
immunocompromised hosts, the reversed halo sign (RHS) has been described on the
pulmonary computed tomographic (CT) scan of patients with mucormycosis. METHODS:
This study reports a single-center experience with PM exclusively in patients
with acute leukemia. Clinical records, laboratory results, and CT scans were
retrospectively analyzed to evaluate the clinical usefulness of the RHS for the
early identification and treatment of PM, with regard to outcomes in these
patients. RESULTS: Between 2003 and 2012, 16 cases of proven PM were diagnosed
among 752 consecutive patients receiving chemotherapy for acute myeloblastic or
lymphoblastic leukemia. At the time PM was diagnosed, all patients but one were
neutropenic. The study of sequential thoracic CT scans showed that during the
first week of the disease, the RHS was observed in 15 of 16 patients (94%).
Initially, other radiologic findings (multiple nodules and pleural effusion) were
less frequent, but appeared later in the course of the disease (6% and 12% before
vs 64% and 55% after the first week). After the diagnosis of PM, median overall
survival was 25 weeks (range, 3-193 weeks), and 6 patients (38%) died before day
90. CONCLUSIONS: In the particular setting of neutropenic leukemia patients with
pulmonary infection, the presence of the RHS on CT was a strong indicator of PM.
It could allow the early initiation of appropriate therapy and thus improve the
outcome.
PMID- 24352352
TI - Randomized trial of central nervous system-targeted antiretrovirals for HIV
associated neurocognitive disorder.
AB - BACKGROUND: Antiretroviral (ARV) medications differentially penetrate across the
blood-brain barrier into central nervous system (CNS) tissues, potentially
influencing their effectiveness in treating brain infection. METHODS: This
randomized controlled clinical trial (RCT) called for 120 participants at 5 study
sites to be randomized 1:1 to CNS-targeted (CNS-T) or non-CNS-T ART. Entry
clinical factors such as ARV experience were balanced across arms using an
adaptive randomization approach. The primary outcome, change in neurocognitive
performance, was measured as the difference in global deficit score (GDS) from
baseline to week 16. RESULTS: The study was terminated early on the
recommendation of its data safety monitoring board on the basis of slow accrual
and a low likelihood of detecting a difference in the primary outcome. No safety
concerns were identified. Of 326 participants screened, 59 met entry criteria and
were randomized. The primary intent-to-treat analysis included 49 participants
who completed week 16. These comprised 39 men and 10 women with a mean age of 44
years (SD, 10 years), and median nadir and current CD4(+) T-cell counts of 175
cells/uL and 242 cells/uL, respectively. The proportional improvement in GDS from
baseline was nonsignificantly larger (7%; 95% confidence interval [CI], -31% to
62%) in the CNS-T arm than in the non-CNS-T arm, representing a treatment effect
size of 0.09 (95% CI, -.48 to .65). Prespecified secondary analysis showed a
trend interaction (P = .087), indicating that participants who had baseline
plasma virologic suppression may have benefited from CNS-T. CONCLUSIONS: This
study found no evidence of neurocognitive benefit for a CNS-T strategy in HIV
associated neurocognitive disorders. A benefit for a subgroup or small overall
benefits could not be excluded. Clinical Trials Registration NCT00624195.
PMID- 24352348
TI - High rate of HIV resuppression after viral failure on first-line antiretroviral
therapy in the absence of switch to second-line therapy.
AB - In a randomized comparison of nevirapine or abacavir with zidovudine plus
lamivudine, routine viral load monitoring was not performed, yet 27% of
individuals with viral failure at week 48 experienced resuppression by week 96
without switching. This supports World Health Organization recommendations that
suspected viral failure should trigger adherence counseling and repeat
measurement before a treatment switch is considered.
PMID- 24352353
TI - Interferon-gamma release assays in solid organ transplant recipients: everything
begins with a single small step.
PMID- 24352354
TI - Extent and consequences of antibody formation against adalimumab in patients with
psoriasis: one-year follow-up.
AB - IMPORTANCE: In a previously reported cohort of 29 patients with plaque-type
psoriasis followed up for 24 weeks, clinically relevant antidrug antibody (ADA)
to adalimumab was frequently found. Long-term data were lacking. We now present
the extension of this study: 80 patients followed up for 1 year. OBJECTIVES: To
assess the extent of ADA and its clinical consequences after 24 weeks of
adalimumab treatment for psoriasis in a cohort of 80 patients. DESIGN, SETTING,
AND PARTICIPANTS: A multicenter cohort study, performed in the outpatient
dermatology clinic of 2 academic hospitals, included 80 sequential patients
receiving adalimumab therapy for plaque-type psoriasis and had a follow-up of 1
year. Outcome assessors were not aware of the presence of antibodies to
adalimumab or the adalimumab serum concentration when assessing patients'
Psoriasis Area and Severity Index (PASI), and personnel analyzing serum samples
were blinded to patients' PASI. INTERVENTIONS: For 80 patients treated with
adalimumab for psoriasis, disease severity (PASI) was assessed, blood samples
were collected, and adalimumab and ADA concentrations was determined at baseline
and at weeks 12, 24, and 52. MAIN OUTCOMES AND MEASURES: Patient PASI and
adalimumab and ADA concentrations. RESULTS: Antidrug antibody formed in 49% of
patients, before week 24 in 90% of them. Adalimumab and ADA concentrations,
clinical response and ADA concentration, and adalimumab concentration and
clinical response had correlations of -0.872, -0.606, and 0.519, respectively.
The adalimumab dose interval was shortened because of lack of efficacy in 15
patients, 7 with and 8 without ADA; improvement in responder status occurred in 1
of 7 and 4 of 8, respectively. CONCLUSIONS AND RELEVANCE: Patients with no ADA
formation in the first 24 weeks of treatment have little chance of it in the
following 24 weeks. The presence of ADA is strongly correlated with adalimumab
concentration and greatly influences clinical response. If ADA is present, dose
interval shortening is less useful.
PMID- 24352356
TI - Two segregated columnar stack platinum-bis-dithiolene molecule solids showing
spin-Peierls-type transition above room temperature.
AB - Two new one-dimensional (1-D) compounds, [CH3-BzPy][Pt(mnt)2] (1) and [CH3-BzPy
d5][Pt(mnt)2] (2) (CH3-BzPy(+) = 1-N-(4-CH3-benzyl)pyridinium and the pyridine in
CH3-BzPy(+) was replaced by pyridine-d5 to give the CH3-BzPy-d5(+); mnt(2-) =
maleonitriledithiolate), were synthesized and characterized. 1 and 2 show similar
magnetic behavior in 1.8-400 K; they experience a spin-Peierls-type transition
around 320 K and show a uniform antiferromagnetic S = 1/2 chain behavior in high
temperature (HT) phase, a spin gap feature in low temperature (LT) phase. A
symmetry breaking structural phase transition is associated with the spin-Peierls
type transition. Two isostructural compounds crystallize in space group P2(1)/c
in HT phase, with a = 12.3066(8) A, b = 27.0522(18) A, c = 7.4248(4) A, beta =
104.204(6) degrees and V = 2396.3(3) A(3) for 1 versus a = 12.3331(9) A, b =
27.087(4) A, c = 7.4501(9) A, beta = 104.149(13) degrees and V = 2413.3(6) A(3)
for 2 at 353 K, while space group P1[combining macron] in LT phase, with a =
7.3203(10) A, b = 12.2816(16) A, c = 26.904(4) A, alpha = 88.500(4) degrees ,
beta = 86.731(4) degrees , gamma = 75.421(4) degrees and V = 2337.0(5) A(3) for
1 versus a = 7.3308(8) A, b = 12.2848(13) A, c = 26.930(3) A, alpha = 88.479(3)
degrees , beta = 86.652(4) degrees , gamma = 75.563(3) degrees and V = 2344.5(4)
A(3) for 2 at 296 K. DSC measurements revealed 1 and 2 showing almost the same
T(C). This observation is distinction from the [Ni(mnt)2](-)-based spin-Peierls
type analogues [CH3-BzPy][Ni(mnt)2] and [CH3-BzPy-d5][Ni(mnt)2] where the
deuteration leads to T(C) up shifting 2.3 K.
PMID- 24352355
TI - The prevalence of sperm with large nuclear vacuoles is a prognostic tool in the
prediction of ICSI success.
AB - PURPOSE: To investigate if there is a correlation between the prevalence of sperm
with large nuclear vacuoles (LNV) and intracytoplasmic sperm injection (ICSI)
outcomes. METHODS: Two hundred male patients undergoing ICSI had their sperm
morphology evaluated through motile sperm organelle morphology examination
(MSOME) and the percentage of LNV sperm was recorded and correlated to the ICSI
outcomes. RESULTS: The percentage of sperm with LNV negatively influenced the
blastocyst formation (S: 16.9, R(2): 20.5%, p = 0.004) and implantation (S: 34.7,
R(2): 26.2%, p = 0.001). There were significant differences in the percentage of
sperm with LNV between patients in which pregnancy was achieved or not (22.2% vs.
28.4%, p < 0.001) and in patients with ongoing pregnancy or not (22.4% vs. 28.5%,
p < 0.001). The incidence of sperm with LNV was determinant to the decreased odds
of pregnancy (OR: 0.74, p < 0.001) and increased odds of miscarriage (OR: 1.46, p
< 0.001). The area under the curve (AUC) was sufficient to distinguish between
couples which did achieve pregnancy or not (AUC: 0.922, p < 0.001). CONCLUSIONS:
The MSOME is a prognostic tool in the prediction of ICSI success and could be
used to select patients that should have their sperm selected by MSOME for ICSI.
PMID- 24352357
TI - Cancer immunotherapy.
PMID- 24352358
TI - Medical imaging: Removing the blindfold.
PMID- 24352359
TI - Adoptive cell therapy: Honing that killer instinct.
PMID- 24352360
TI - Cancer vaccines: Material breach.
PMID- 24352361
TI - Calling cells to arms.
PMID- 24352362
TI - Bacteriology: a caring culture.
PMID- 24352363
TI - Drug development: Releasing the brakes.
PMID- 24352364
TI - Q&A: Evidence presenter. Interview by Marian Turner.
PMID- 24352365
TI - A continuous-flow high-throughput microfluidic device for airborne bacteria PCR
detection.
AB - Rapid analysis of airborne pathogens plays a critical role in early warning of
spreading infectious diseases, which is essential for public health and disease
prevention. Herein we report an integrated microfluidic device that can perform
airborne pathogen capture, enrichment and continuous-flow high-throughput gene
analysis. The device was validated by six frequently encountered bacteria and
shows great potential in environmental analysis and for public health protection.
PMID- 24352366
TI - Referrals by general practitioners for suspicious skin lesions: the urgency of
training.
AB - Skin cancer is common among white populations and rapid increases in incidence
are being observed in many countries, leading to a large burden on healthcare
systems. Unnecessary referrals from general practitioners (GPs) may contribute to
this burden. The aim of this study was to analyse the quality of referrals from
GPs of patients with skin tumours. Referral letters for 734 patients were
collected. The proposed diagnoses were compared with definitive diagnosis made by
dermatologists. In 44.5%, lesions appeared to be benign. Malignant skin tumours
were poorly recognised by GPs and seborrheic keratoses were often mistaken for
naevi (33.6%). Furthermore, with total body examination, dermatologists found 111
additional malignant lesions. We discussed several recommendations to minimise
unnecessary referrals as well as the future role of GPs in skin cancer care.
PMID- 24352367
TI - Altered mechano-chemical environment in hip articular cartilage: effect of
obesity.
AB - The production of extracellular matrix (ECM) components of articular cartilage is
regulated, among other factors, by an intercellular signaling mechanism mediated
by the interaction of cell surface receptors (CSR) with insulin-like growth
factor-1 (IGF-1). In ECM, the presence of binding proteins (IGFBP) hinders IGF-1
delivery to CSR. It has been reported that levels of IGF-1 and IGFBP in obese
population are, respectively, lower and higher than those found in normal
population. In this study, an experimental-numerical approach was adopted to
quantify the effect of this metabolic alteration found in obese population on the
homeostasis of femoral hip cartilage. A new computational model, based on the
mechano-electrochemical mixture theory, was developed to describe competitive
binding kinetics of IGF-1 with IGFBP and CSR, and associated glycosaminoglycan
(GAG) biosynthesis. Moreover, a gait analysis was carried out on obese and normal
subjects to experimentally characterize mechanical loads on hip cartilage during
walking. This information was deployed into the model to account for effects of
physiologically relevant tissue deformation on GAG production in ECM. Numerical
simulations were performed to compare GAG biosynthesis in femoral hip cartilage
of normal and obese subjects. Results indicated that the lower ratio of IGF-1 to
IGFBP found in obese population reduces cartilage GAG concentration up to 18 %
when compared to normal population. Moreover, moderate physical activity, such as
walking, has a modest beneficial effect on GAG production. The findings of this
study suggest that IGF-1/IGFBP metabolic unbalance should be accounted for when
considering the association of obesity with hip osteoarthritis.
PMID- 24352369
TI - Conformational and mechanical changes of DNA upon transcription factor binding
detected by a QCM and transmission line model.
AB - A novel quartz crystal microbalance (QCM) analytical method is developed based on
the transmission line model (TLM) algorithm to analyze the binding of
transcription factors (TFs) to immobilized DNA oligoduplexes. The method is used
to characterize the mechanical properties of biological films through the
estimation of the film dynamic shear moduli, G and G, and the film thickness.
Using the Saccharomyces cerevisiae transcription factor Haa1 (Haa1DBD) as a
biological model two sensors were prepared by immobilizing DNA oligoduplexes, one
containing the Haa1 recognition element (HRE(wt)) and another with a random
sequence (HRE(neg)) used as a negative control. The immobilization of DNA
oligoduplexes was followed in real time and we show that DNA strands initially
adsorb with low or non-tilting, laying flat close to the surface, which then lift
off the surface leading to final film tilting angles of 62.9 degrees and 46.7
degrees for HRE(wt) and HRE(neg), respectively. Furthermore we show that the
binding of Haa1DBD to HRE(wt) leads to a more ordered and compact film, and
forces a 31.7 degrees bending of the immobilized HRE(wt) oligoduplex. This work
demonstrates the suitability of the QCM to monitor the specific binding of TFs to
immobilized DNA sequences and provides an analytical methodology to study protein
DNA biophysics and kinetics.
PMID- 24352368
TI - Reconciling variable findings of white matter integrity in major depressive
disorder.
AB - Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM)
integrity in major depressive disorder (MDD), with several studies reporting
differences between depressed patients and controls. However, these findings are
variable and taken from relatively small studies often using suboptimal analytic
approaches. The presented DTI study examined WM integrity in large samples of
medication-free MDD patients (n=134) and healthy controls (n=54) using voxel
based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and
rigorous statistical thresholds. Compared with health control subjects, MDD
patients show no significant differences in fractional anisotropy, radial
diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the
TBSS approach. Our findings suggest that disrupted WM integrity does not have a
major role in the neurobiology of MDD in this relatively large study using
optimal imaging acquisition and analysis; however, this does not eliminate the
possibility that certain patient subgroups show WM disruption associated with
depression.
PMID- 24352370
TI - Prenatal administration of retinoic acid increases the trophoblastic insulin-like
growth factor 2 protein expression in the nitrofen model of congenital
diaphragmatic hernia.
AB - BACKGROUND: The high mortality rate in congenital diaphragmatic hernia (CDH) is
attributed to pulmonary hypoplasia (PH). Insulin-like growth factor 2 (IGF2) is
an important regulator of fetal growth. The highest levels of IGF2 expression are
found in the placenta, which are negatively regulated by decidual retinoid acid
receptor alpha (RARalpha). It has been demonstrated that prenatal administration
of retinoic acid (RA) suppresses decidual RARalpha expression. Previous studies
have further shown that prenatal administration of RA can reverse PH in nitrofen
induced CDH model. In IGF2 knockout animals, low levels of IGF2 are associated
with decreased placental growth and PH. We therefore hypothesized that nitrofen
decreases trophoblastic IGF2 expression and prenatal administration of RA
increases it through decidual RARalpha in the nitrofen-induced CDH model.
METHODS: Pregnant rats were exposed to either olive oil or nitrofen on day 9 of
gestation (D9). RA was given intraperitoneally on D18, D19 and D20. Fetuses were
harvested on D21 and divided into three groups: control, CDH and nitrofen+RA.
Immunohistochemistry was performed to evaluate decidual RARalpha and
trophoblastic IGF2 expression. Protein levels of IGF2 in serum, intra-amniotic
fluid and left lungs were measured by enzyme-linked immunosorbent assay. RESULTS:
Significant growth retardation of placenta and left lungs was observed in the CDH
group compared to control and nitrofen+RA group. Markedly increased decidual
RARalpha and decreased IGF2 immunoreactivity were found in the CDH group compared
to control and nitrofen+RA group. Significantly decreased IGF2 protein levels
were detected in serum, intra-amniotic fluid and left lungs in the CDH group
compared to control and nitrofen+RA group. CONCLUSION: Our findings suggest that
nitrofen may disturb trophoblastic IGF2 expression through decidual RARalpha
resulting in retarded placental growth and PH in the nitrofen-induced CDH.
Prenatal administration of RA may promote lung and placental growth by increasing
trophoblastic IGF2 expression.
PMID- 24352372
TI - Dynamic transpedicular stabilisation and decompression in single-level
degenerative anterolisthesis and stenosis.
AB - BACKGROUND: Different treatment options exist for symptomatic single-level
degenerative anterolisthesis and stenosis. While simple micro-decompression has
been advocated lately, most authors recommend posterior decompression with
fusion. In recent years, decompression and dynamic transpedicular stabilisation
has been introduced for this indication. The aim of this study was to evaluate
the safety and efficacy of decompression and dynamic transpedicular stabilisation
with the Dynesys(r) system in single-level degenerative anterolisthesis and
stenosis. METHODS: Thirty consecutive patients with symptomatic single-level
degenerative anterolisthesis and stenosis without scoliosis underwent
decompression and single-level Dynesys stabilisation at the level of degenerative
anterolisthesis. Patients were followed prospectively for 24 months with
radiographs, Oswestry Disability Index scores, visual analogue scale (VAS) for
back and leg pain, and estimated pain-free walking distance. RESULTS: At the 2
year follow-up, back pain was reduced from 6.5 preoperatively to 2.5, leg pain
from 5.4 to 0.6. The pain-free walking distance was estimated at 500 m
preoperatively and at over 2 km after 2 years, while the ODI decreased from 54 %
to 18 %. Screw loosening was found in 2/30 cases. Symptomatic adjacent segment
disease was found in 3/30 patients between 12 and 24 months postoperatively.
CONCLUSIONS: Single-level Dynesys stabilisation combined with single- or multi
level decompression seems to be a safe and efficient treatment option in single
level degenerative anterolisthesis and stenosis over an observation period of 2
years, avoiding iliac crest or local bone grafting required by fusion procedures.
However, it does not seem to avoid adjacent segment disease.
PMID- 24352371
TI - Abnormal neural crest innervation in Sox10-Venus mice with all-trans retinoic
acid-induced anorectal malformations.
AB - BACKGROUND/PURPOSE: Despite technical advances in the surgical/medical care of
anorectal malformation (ARM), persistent unsatisfactory postoperative bowel habit
has been attributed to histopathologic abnormalities of the distal rectum/pouch
(DRP) and hypoplasia of anal sphincter muscles (ASM). We used Sox10-Venus mice
with ARM induced by all-trans retinoic acid (ATRA) to investigate neural crest
cell (NCC) innervation in the DRP and ASM. METHOD: Pregnant Sox10-Venus mice were
administered single doses of 50, 70, or 100 mg/kg of ATRA on embryonic day 8.5
(E8.5) then sacrificed on either E16.5 or E19.5. Bowel specimens comprising the
anorectum were examined using fluorescence microscopy without immunohistochemical
staining (FMIS). Anti-PGP9.5 was used to delineate ganglion cells and anti-SMA
for smooth muscles. RESULTS: The appropriate dose of ATRA for inducing ARM was 50
mg/kg. Under FMIS, all ARM embryos (n = 5; all high type; 3 male:2 female) had
less NCC innervation with thick Venus-positive nerve fibers in the DRP compared
with normal embryos (n = 8); there was abnormal NCC innervation in the DRP and
absent ASM in ARM mice. CONCLUSION: We are the first to delineate abnormal
enteric nervous system innervation in the DRP of ARM mice without using
immunohistochemical staining techniques thus allowing specimens to be examined
without any distortion.
PMID- 24352373
TI - Co-transplantation of bone marrow-derived mesenchymal stem cells and nanospheres
containing FGF-2 improve cell survival and neurological function in the injured
rat spinal cord.
AB - BACKGROUND: Spinal cord injury (SCI) is a devastating and irreversible event, and
much research using fibroblast growth factor-2 (FGF-2) has been performed to test
its capacity to blunt the effects of SCI as well as to provide an environment
conducive for SCI repair. METHODS: We tested how the in vitro release of FGF-2
from heparin-conjugated poly(L-lactide-co-glycolide) (PLGA)-conjugated
nanospheres (HCPNs) affected the growth of human bone marrow-derived mesenchymal
stem cells (hBMSCs), as well as the effects of their co-transplantation in an
animal model of SCI. RESULTS: Our results showed that sustained, long-term
release of FGF-2 from HCPNs significantly increased hBMSCs proliferation in
vitro, and that their co-transplantation following rat SCI lead to increased
functional improvement, a greater amount of hBMSCs surviving transplantation, and
a greater density of neurofilament-positive cells in the injury epicenter.
CONCLUSION: These results suggest a proliferative, protective, and neural
inductive potential of FGF-2 for transplanted hBMSCs, as well as a possible role
for sustained FGF-2 delivery along with hBMSCs transplantation in the injured
spinal cord. Future studies will be required to ascertain the safety FGF-2
containing HCPNs before clinical application.
PMID- 24352374
TI - Investigation of organic matter migrating from polymeric pipes into drinking
water under different flow manners.
AB - Polymeric pipes, such as unplasticized polyvinyl chloride (uPVC) pipes,
polypropylene random (PPR) pipes and polyethylene (PE) pipes are increasingly
used for drinking water distribution lines. Plastic pipes may include some
additives like metallic stabilizers and other antioxidants for the protection of
the material during its production and use. Thus, some compounds can be released
from those plastic pipes and cast a shadow on drinking water quality. This work
develops a new procedure to investigate three types of polymer pipes (uPVC, PE
and PPR) with respect to the migration of total organic carbon (TOC) into
drinking water. The migration test was carried out in stagnant conditions with
two types of migration processes, a continuous migration process and a successive
migration process. These two types of migration processes are specially designed
to mimic the conditions of different flow manners in drinking water pipelines,
i.e., the situation of continuous stagnation with long hydraulic retention times
and normal flow status with regular water renewing in drinking water networks.
The experimental results showed that TOC release differed significantly with
different plastic materials and under different flow manners. The order of
materials with respect to the total amount of TOC migrating into drinking water
was observed as PE > PPR > uPVC under both successive and continuous migration
conditions. A higher amount of organic migration from PE and PPR pipes was likely
to occur due to more organic antioxidants being used in pipe production. The
results from the successive migration tests indicated the trend of the migration
intensity of different pipe materials over time, while the results obtained from
the continuous migration tests implied that under long stagnant conditions, the
drinking water quality could deteriorate quickly with the consistent migration of
organic compounds and the dramatic consumption of chlorine to a very low level.
Higher amounts of TOC were released under the continuous migration tests.
PMID- 24352376
TI - Detection of enterovirus in the islet cells of patients with type 1 diabetes:
what do we learn from immunohistochemistry?
PMID- 24352375
TI - IL-17A increases the expression of proinflammatory chemokines in human pancreatic
islets.
AB - AIMS/HYPOTHESIS: Cytotoxic T cells and macrophages contribute to beta cell
destruction in type 1 diabetes at least in part through the production of
cytokines such as IL-1beta, IFN-gamma and TNF-alpha. We have recently shown the
IL-17 pathway to be activated in circulating T cells and pancreatic islets of
type 1 diabetes patients. Here, we studied whether IL-17A upregulates the
production of chemokines by human pancreatic islets, thus contributing to the
build-up of insulitis. METHODS: Human islets (from 18 donors), INS-1E cells and
islets from wild-type and Stat1 knockout mice were studied. Dispersed islet cells
were left untreated, or were treated with IL-17A alone or together with IL
1beta+IFN-gamma or TNF-alpha+IFN-gamma. RNA interference was used to knock down
signal transducer and activator of transcription 1 (STAT1). Chemokine expression
was assessed by quantitative RT-PCR, ELISA and histology. Cell viability was
evaluated with nuclear dyes. RESULTS: IL-17A augmented IL-1beta+IFN-gamma- and
TNF-alpha+IFN-gamma-induced chemokine mRNA and protein expression, and apoptosis
in human islets. Beta cells were at least in part the source of chemokine
production. Knockdown of STAT1 in human islets prevented cytokine- or IL
17A+cytokine-induced apoptosis and the expression of particular chemokines, e.g.
chemokine (C-X-C motif) ligands 9 and 10. Similar observations were made in
islets isolated from Stat1 knockout mice. CONCLUSIONS/INTERPRETATION: Our
findings indicate that IL-17A exacerbates proinflammatory chemokine expression
and secretion by human islets exposed to cytokines. This suggests that IL-17A
contributes to the pathogenesis of type 1 diabetes by two mechanisms, namely the
exacerbation of beta cell apoptosis and increased local production of chemokines,
thus potentially aggravating insulitis.
PMID- 24352378
TI - A single-phase white-emitting Ca2SrAl2O6:Ce3+,Li+,Mn2+ phosphor with energy
transfer for UV-excited WLEDs.
AB - A series of Ca2SrAl2O6:Ce(3+),Li(+),Mn(2+) phosphors have been synthesized by
traditional solid state reactions. The structure and photoluminescence properties
of the samples together with the energy transfer from Ce(3+) to Mn(2+) ions have
been investigated in detail. The obtained phosphors can be excited efficiently by
UV excitation and exhibit a broad blue-green emission band peaking at 470 nm and
an orange-red emission band at 610 nm, which result from the f-d transition of
the Ce(3+) and the (4)T1-(6)A1 transition of the Mn(2+) ions, respectively. By
varying the doping concentration of the Mn(2+) ion, a series of tunable colors
including white are obtained at an irradiation of 355 nm. The possible energy
transfer mechanism was proposed in terms of the experimental results and analysis
of photoluminescence spectra and decay curves of the phosphors. The critical
distance between the Ce(3+) and Mn(2+) ions has been calculated by both the
concentration quenching method and the spectral overlap method. Preliminary
studies on the properties of the phosphor indicated that our prepared
Ca2SrAl2O6:Ce(3+),Li(+),Mn(2+) phosphor might have potential application as a
single-phase white-emitting phosphor for WLEDs.
PMID- 24352377
TI - Mitigation of sociocommunicational deficits of autism through oxytocin-induced
recovery of medial prefrontal activity: a randomized trial.
AB - IMPORTANCE: Sociocommunicational deficits make it difficult for individuals with
autism spectrum disorders (ASD) to understand communication content with
conflicting verbal and nonverbal information. Despite growing prospects for
oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence
exists for oxytocin's beneficial effects on this core symptom of ASD. This is
slowing clinical application of the neuropeptide. OBJECTIVE: To directly examine
whether oxytocin has beneficial effects on the sociocommunicational deficits of
ASD using both behavioral and neural measures. DESIGN, SETTING, AND PARTICIPANTS:
At the University of Tokyo Hospital, we conducted a randomized, double-blind,
placebo-controlled, within-subject-crossover, single-site experimental trial in
which intranasal oxytocin and placebo were administered. A total of 40 highly
functioning men with ASD participated and were randomized in the trial.
INTERVENTIONS: Single-dose intranasal administration of oxytocin (24 IU) and
placebo. MAIN OUTCOMES AND MEASURES: Using functional magnetic resonance imaging,
we examined effects of oxytocin on behavioral neural responses of the
participants to a social psychological task. In our previous case-control study
using the same psychological task, when making decisions about social information
with conflicting verbal and nonverbal contents, participants with ASD made
judgments based on nonverbal contents less frequently with longer time and could
not induce enough activation in the medial prefrontal cortex. Therefore, our main
outcomes and measures were the frequency of the nonverbal information-based
judgments (NVJs), the response time for NVJs, and brain activity of the medial
prefrontal cortex during NVJs. RESULTS: Intranasal oxytocin enabled the
participants to make NVJs more frequently (P = .03) with shorter response time (P
= .02). During the mitigated behavior, oxytocin increased the originally
diminished brain activity in the medial prefrontal cortex (P < .001). Moreover,
oxytocin enhanced functional coordination in the area (P < .001), and the
magnitude of these neural effects was predictive of the behavioral effects (P <=
.01). CONCLUSIONS AND RELEVANCE: These findings provide the first neurobiological
evidence for oxytocin's beneficial effects on sociocommunicational deficits of
ASD and give us the initial account for neurobiological mechanisms underlying any
beneficial effects of the neuropeptide. TRIAL REGISTRATION: umin.ac.jp/ctr
Identifier: UMIN000002241 and UMIN000004393.
PMID- 24352379
TI - PACS in 2018: an autopsy.
PMID- 24352380
TI - Electrocautery interference with intraoperative capnography during neurosurgery.
PMID- 24352381
TI - Engineering protein thermostability using a generic activity-independent
biophysical screen inside the cell.
AB - Protein stability is often a limiting factor in the development of commercial
proteins and biopharmaceuticals, as well as for biochemical and structural
studies. Unfortunately, identifying stabilizing mutations is not trivial since
most are neutral or deleterious. Here we describe a high-throughput colony-based
stability screen, which is a direct and biophysical read-out of intrinsic protein
stability in contrast to traditional indirect activity-based methods. By
combining the method with a random mutagenesis procedure, we successfully
identify thermostable variants from 10 diverse and challenging proteins,
including several biotechnologically important proteins such as a single-chain
antibody, a commercial enzyme and an FDA-approved protein drug. We also show that
thermostabilization of a protein drug using our approach translates into dramatic
improvements in long-term stability. As the method is generic and activity
independent, it can easily be applied to a wide range of proteins.
PMID- 24352382
TI - Small bowel transglutaminase 2-specific IgA deposits in dermatitis herpetiformis.
AB - Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac
disease. Untreated coeliac disease patients are known to have transglutaminase 2
(TG2)-targeted IgA deposits in the small bowel mucosa. To evaluate whether
similar intestinal IgA deposits are also present in DH and whether the deposits
disappear with gluten-free diet, 47 untreated and 27 treated DH patients were
studied. Seventy-nine percent of untreated and 41% of the treated DH patients had
TG2-specific IgA deposits in the small bowel, and the presence of the deposits
showed a significant association with the degree of small bowel villous atrophy
(p < 0.001). Other coeliac-disease related inflammatory markers were also
investigated, and the density of small bowel mucosal intraepithelial
gammadelta(+) T cells was increased in 91% of untreated and 73% of treated DH
patients. The results show that the majority of untreated DH patients have
similar gluten-dependent TG2-specific IgA deposits the small bowel mucosa as
coeliac disease patients.
PMID- 24352384
TI - Clarifications, guidelines and questions about the dental bleaching "associated"
with orthodontic treatment.
AB - With regard to the best moment for carrying out or recommending dental bleaching
to orthodontic patients, some explanations and orientations are given in order to
answers the following questions: 1) Why orthodontic treatment completion is
considered the best opportunity for carrying out the procedure? 2) Why dental
bleaching should not be performed immediately before orthodontic treatment? 3) If
that would be possible at any special case, what would that be? 4) Why dental
bleaching should not be performed during orthodontic treatment? 5) If that would
be possible at any special case, what would that be? This article highlights why
it is essential to protect both the mucosa and the cervical region, regardless of
the moment when dental bleaching is performed, whether associated with
orthodontic treatment or not. The "how", "why" and "if" it is or not convenient
to perform dental bleaching before orthodontic treatment are still a matter of
clinical suggestion, as it is a procedure that is under analysis, empirical
knowledge waiting for scientific proof or disproof! Although tooth enamel has
adamantine fluid flowing within it, providing a specific metabolism that is
peculiar to its own and which could scientifically explain and base the option of
carrying out teeth whitening before and during orthodontic treatment, we must
still be very careful.
PMID- 24352385
TI - Assessment of pain experience in adults and children after bracket bonding and
initial archwire insertion.
AB - INTRODUCTION: Ninety five percent of orthodontic patients routinely report pain,
due to alterations in the periodontal ligament and surrounding soft tissues, with
intensity and prevalence varying according to age. OBJECTIVE: This study aimed to
assess toothache and buccal mucosal pain in adults and children during two
initial phases of the orthodontic treatment. METHODS: The intensity of toothache
and buccal mucosal pain reported by 20 patients, 10 children (11-13 years) and 10
adults (18-37 years) was recorded with the aid of a Visual Analog Scale (VAS),
during 14 days--7 days with bonded brackets only and 7 days with the initial
archwire inserted. RESULTS: There was no significant difference in pain intensity
among adults and children. After bracket bonding, 50% of the children and 70% of
the adults reported pain. 70% of both groups reported pain after initial archwire
insertion. While adults reported constant, low intensity, buccal mucosal pain,
the children showed great variation of pain intensity, but with a trend towards
decreasing pain during the assessment period. After initial archwire insertion
the peaks of toothache intensity and prevalence occurred 24 hours in children and
48 hours in adults. CONCLUSIONS: In general, children reported pain less
frequently than adults did, though with greater intensity.
PMID- 24352386
TI - Class II malocclusion treatment with the Herbst appliance in patients after the
growth peak.
AB - OBJECTIVE: The objective of this study was to evaluate dentoskeletal effects in
the treatment of Class II malocclusion performed with the Herbst appliance in
patients at post-peak stage of growth. METHODS: The sample consisted of 16
patients with Class II malocclusion and average initial and final ages of 14.04
(ranging from 11.50 to 35.66) and 17.14 (ranging from 13.68 to 38.64) years,
respectively, who were treated for an mean time of 2.52 years. Lateral
cephalograms were obtained at treatment onset (T1) and completion (T2) to
evaluate the effects of therapy. Initial dental casts were also used to evaluate
the overjet and the anteroposterior severity of molar relationship at treatment
onset. The cephalometric changes between initial and final stages were compared
by means of the non-parametric Wilcoxon test. RESULTS: The results showed that
the Herbst appliance did not promote significant changes in the maxillary
component and the effective length of the mandible significantly increased
without improving the maxillomandibular relationship. Changes in the maxillary
and mandibular dentoalveolar components revealed that the maxillary incisors
exhibited retrusion and lingual tipping, while the mandibular incisors presented
increased protrusion and buccal tipping. The dental relationships exhibited
significant improvements with the treatment. CONCLUSION: Based on the present
results, it was concluded that the effects of treatment performed with the Herbst
appliance in patients at post-peak stage of growth are predominantly of
dentoalveolar nature.
PMID- 24352387
TI - Effects of mandibular protraction appliance associated to fixed appliance in
adults.
AB - OBJECTIVE: This retrospective study aimed to conduct a cephalometric evaluation
of the skeletal, dental and soft tissue effects resulting from treatment of adult
patients presenting Class II malocclusion, performed with a Mandibular
Protraction Appliance (MPA) combined with a fixed orthodontic appliance. METHODS:
The sample consisted of teleradiographs obtained before and after treatment of 9
adult patients (initial mean age of 22.48 years) with bilateral Class II,
division 1, malocclusion. Paired t test (p < 0.05) was applied to compare initial
and final values. RESULTS: t test revealed an increase in anteroinferior facial
height and posterior facial height. The dental changes include: extrusion of
upper incisors, buccal inclination, protrusion of lower incisors, mesialization
and extrusion of mandibular molars. Regarding the soft tissue component, there
was an increase in nasolabial angle in addition to upper lip retrusion.
CONCLUSIONS: The effects of treating Class II malocclusion adult patients, by
means of using Mandibular Protraction Appliance (MPA) combined with a fixed
appliance were mostly observed in the mandibular arch, and consisted of buccal
inclination, protrusion and intrusion of incisors, and mesialization and
extrusion of the molars.
PMID- 24352388
TI - Cephalometric evaluation of the predictability of bimaxillary surgical
orthodontic treatment outcomes in long face pattern patients: a retrospective
study.
AB - OBJECTIVE: The aim of this study was to compare by means of McNamara as well as
Legan and Burstone's cephalometric analyses, both manual and digitized (by
Dentofacial Planner Plus and Dolphin Image software) prediction tracings to post
surgical results. METHODS: Pre and post-surgical teleradiographs (6 months) of 25
long face patients subjected to combined orthognathic surgery were selected.
Manual and computerized prediction tracings of each patient were performed and
cephalometrically compared to post-surgical outcomes. This protocol was repeated
in order to evaluate the method error and statistical evaluation was conducted by
means of analysis of variance and Tukey's test. RESULTS: A higher frequency of
cephalometric variables, which were not statistically different from the actual
post-surgical results for the manual method, was observed. It was followed by
DFPlus and Dolphin software; in which similar cephalometric values for most
variables were observed. CONCLUSION: It was concluded that the manual method
seemed more reliable, although the predictability of the evaluated methods
(computerized and manual) proved to be reasonably satisfactory and similar.
PMID- 24352389
TI - Factors related to orthodontic treatment time in adult patients.
AB - INTRODUCTION: The length of time that it takes an orthodontist to treat adult
patients varies widely. OBJECTIVE: The aim of this study was to investigate how
different variables influence treatment time. METHODS: Seventy clinical case
reports of successfully treated adult patients were examined. The patients were
selected from 4,723 records held by three experienced orthodontists. The
influence exerted by the following variables on treatment time was assessed: age,
sex, facial pattern, severity of malocclusion (measured by the PAR index),
sagittal relationship of canines, type of brackets (ceramic or metal), tooth
extractions, missed appointments and orthodontic appliance issues/breakages, the
latter being the dependent variable. Assessment was performed by multiple linear
regression analysis, followed by the stepwise method with p < 0.05. RESULTS: The
number of times a patient missed their appointment (no-show) (R2 = 14.4%, p <
0.0001) and the number of appliance issues/breakages (R2 = 29.71%, p = 0.0037)
significantly affected variability in treatment time, and these two variables
together can predict 43.75% (R2 total) of the overall variability in treatment
time. Other factors, such as canine relationship at the beginning of treatment,
bracket type (metal or ceramic), tooth extractions, age at start of treatment,
severity of the initial malocclusion, sex and facial pattern had no significant
bearing on treatment time. CONCLUSIONS: The duration of orthodontic treatment in
adults, when performed by experienced orthodontists, is mainly influenced by
factors related to patient compliance. However, several factors which were not
included in this study may contribute to variability in orthodontic treatment
time.
PMID- 24352390
TI - Effects of chin advancement surgery in hyoid bone and tongue positions and in the
dimension of the oropharynx.
AB - INTRODUCTION: Advancement genioplasty has been increasingly indicated for the
correction of anterior mandibular deficiency as it balances the patient's profile
and generates functional changes. OBJECTIVE: Thus, the aim of this study was to
assess the effects of advancement genioplasty in the oropharyngeal size and in
the position of the hyoid bone and tongue. METHODS: The sample comprised 22
lateral cephalometric radiographs of 11 individuals who had undergone advancement
genioplasty alone. Eleven of these radiographs depicted the immediate
preoperative period (T0) and the other 11 the postoperative period after at least
four months (T1). The radiographs were scanned and exported to the Radiocef
Studio 2.0(r) software (Radio Memory Ltda., Belo Horizonte, MG, Brazil). The
landmarks were then identified and automatically measured by the program.
RESULTS: The results showed statistically significant differences between the
horizontal position of the hyoid bone and tongue and in the oropharyngeal size.
The hyoid bone and tongue were repositioned anteriorly after surgery (p = 0.01),
thereby increasing the dimension of the oropharyngeal airspace (p = 0.01).
CONCLUSIONS: The oropharyngeal dimension increased as the tongue base and hyoid
bone were repositioned more anteriorly.
PMID- 24352391
TI - Auditory characteristics of individuals with temporomandibular dysfunctions and
dentofacial deformities.
AB - OBJECTIVE: To investigate whether there is any relationship between otological as
well as vestibular symptoms, audiological findings and type of temporomandibular
disorder (articular, muscular and mixed); and to check the distribution of the
temporomandibular disorders (TMD) dysfunction degree in the research population.
METHODS: A retrospective study involving 30 patients of both sexes, aged between
18 and 49 years old, diagnosed with TMD and dentofacial deformities, who were
subject to clinical evaluation (muscle palpation, auscultation of
temporomandibular joint during mandibular motion and measurement of jaw
movement), audiological testing (pure tone audiometry and immittance testing) and
two questionnaires, one on otological and vestibular symptoms and the other on
TMD anamnesis. Based on both the anamnesis questionnaire and the clinical
assessment, the subjects were divided according to the type and degree of TMD
dysfunction (mild, moderate and severe), and compared regarding the occurrence of
auditory signs and symptoms, vestibular symptoms and audiological findings
according to TMD type. RESULTS: The anamnesis questionnaire demonstrated higher
prevalence (83.33%) of severe TMD. Subjects with mixed TMD had more complaints
about hypoacusis than those with muscular TMD (p < 0.05). The results showed no
change in either audiological and immittance testing for all assessed
individuals. CONCLUSION: Otological symptoms are present in subjects with TMD and
dentofacial deformities, regardless of the classification of TMD (articular,
muscular or mixed). Those with mixed TMD may have higher incidence of complaints
about hypoacusis than subjects with muscular TMD. Further studies are needed to
investigate the relationship between otological symptoms and the different types
of TMD.
PMID- 24352392
TI - Is there correlation between alveolar and systemic bone density?
AB - OBJECTIVE: The present study assessed the correlation between maxillomandibular
alveolar bone density and systemic bone mineral density (BMD). METHODS: Dual
energy X-ray absorptiometry of the anterior and posterior maxillomandibular
alveolar bone, of the standard sites for the measurement of BMD (lumbar spine and
femur) and the third cervical vertebra was performed on 23 middle-aged women.
Periapical radiographs were also obtained, with an aluminum step-wedge as
reference for the digital reading of apical bone density of the upper incisors.
RESULTS: Spearman's correlations coefficients revealed that density in the apical
region was correlated with that of the femoral neck (r = 0.433; p < 0.05); BMDs
of the posterior regions of the mandible and maxilla were significantly
correlated with that of the cervical vertebra (r = 0.554, p <= 0.01 and r =
0.423, p <= 0.05, respectively); and the anterior maxilla was correlated with the
posterior mandible (r = 0.488, p <= 0.05). CONCLUSION: Bone density of the
maxillary alveolar bone was significantly correlated with that of the femoral
neck. Among the bone densities of the alveolar regions, only the anterior maxilla
and the posterior mandible were significantly correlated. The findings suggested
that bone densitometry might be individually and locally evaluated.
PMID- 24352393
TI - Horizontal and vertical maxillary osteotomy stability, in cleft lip and palate
patients, using allogeneic bone graft.
AB - OBJECTIVE: This study was carried out to evaluate maxillary stability after
orthodontic-surgical treatment of patients with cleft lip and palate.
Cephalometric analysis was applied to two different groups, with and without
allogeneic bone graft. METHODS: The sample comprised 48 patients with cleft lip
and palate. The test group comprised 25 patients who, after correction of
maxillary position, received allogeneic bone graft at the gap created by Le Fort
I osteotomy. The control group comprised 23 patients and its surgical procedures
were similar to those applied to the test group, except for the use of bone
graft. Manual cephalometric analysis and comparison between lateral
teleradiographs, obtained at the preoperative phase, immediate postoperative
phase and after a minimum period of six months, were carried out. RESULTS: An
higher horizontal relapse was observed in the control group (p>0.05). There were
no statistically significant differences in vertical relapses between test and
control groups (p<0.05). CONCLUSION: The use of allogeneic bone graft in cleft
lip and palate patients submitted to Le Fort I osteotomy contributed to increase
postoperative stability when compared to surgeries without bone graft.
PMID- 24352394
TI - Comparison of the changes of alveolar bone thickness in maxillary incisor area in
extraction and non-extraction cases: computerized tomography evaluation.
AB - OBJECTIVE: To compare, through computed tomography, alveolar bone thickness
changes at the maxillary incisors area during orthodontic treatment with and
without tooth extraction. METHODS: Twelve patients were evaluated. They were
divided into 2 groups: G1--6 patients treated with extraction of right and left
maxillary first premolars, with mean initial age of 15.83 years and mean
treatment length of 2.53 years; G2--6 patients treated without extraction, with
mean initial age of 18.26 years and mean treatment length of 2.39 years. Computed
tomographies, lateral cephalograms and periapical radiographs were used at the
beginning of the treatment (T1) and 18 months after the treatment had started
(T2). Extraction space closure occurred in the extraction cases. Intragroup and
intergroup comparisons were performed by dependent and independent t test,
respectively. RESULTS: In G1, the central incisor was retracted and uprighted,
while in G2 this tooth showed vestibularization. Additionally, G1 presented a
higher increase of labial alveolar bone thickness at the cervical third in
comparison with G2. The incidence of root resorption did not present significant
differences between groups. CONCLUSION: There were no changes in alveolar bone
thickness when extraction and nonextraction cases were compared, except for the
labial alveolar bone thickness at the cervical third of maxillary incisors.
PMID- 24352395
TI - Translation and cross-cultural adaptation of an instrument designed for the
assessment of quality of life in orthognatic patients.
AB - INTRODUCTION: The Orthognathic Quality of Life Questionnaire (OQLQ) was developed
in 2000 and validated in 2002, aiming at assessing the impact and the benefits of
orthosurgical treatment on patients' quality of life. OBJECTIVE: Cross-culturally
translate into Brazilian Portuguese and back-translate into English a quality of
life instrument, assuring maintenance of its properties. METHODS: At first,
equivalence of concepts and items was discussed by a group of specialists who
scrutinized all questionnaire items. Additionally, four patients in need of
orthosurgical treatment were interviewed by means of the focus group methodology.
Relevance of the questionnaire items was assured prior to its translation which
was carried out by two translators who worked independently. Both translations
were tested in 20 patients and then consolidated. The consolidated questionnaire
version was back-translated into English by two translators who worked
independently, and the consolidated back-translation was assessed by the authors
of the original questionnaire as well as by the researchers. RESULTS: The OQLQ
was translated into Brazilian Portuguese. This translation was tested in a pilot
study comprising 12 patients, aged between 16 and 34 years old. CONCLUSION: The
OQLQ Brazilian Portuguese translation proves to be an appropriate instrument to
assess the impact of dentofacial deformities on the quality of life of patients
in the Brazilian public health system and who are in need of orthosurgical
treatment.
PMID- 24352396
TI - Evaluation of life quality of patients submitted to orthognathic surgery.
AB - OBJECTIVE: To compare changes related to self-esteem and appearance satisfaction
between pre and postsurgical phases in patients undergoing orthognathic surgery
and to assess the quality of life and psychosocial changes of these patients six
months after surgery. METHODS: A longitudinal observational qualitative study was
performed. The sample comprised 15 patients with dentofacial deformities who
underwent orthognathic surgery. One questionnaire and two forms were answered
during pre and postoperative phases. RESULTS: The results showed that 13.3% of
patients demonstrated self-esteem improvement, especially in relation to
appearance satisfaction. Improvements were also noted in social, occupational and
family relationships. With regard to the assessment of quality of life, according
to the World Health Organization questionnaire, the lowest improvement averages
corresponded to environmental control. CONCLUSION: Orthognathic surgery brings
along many emotional changes that should be considered before and after surgery,
since the patients' psychological state may be favorable and/or unfavorable
during recovery, influencing their quality of life, self-esteem and appearance
satisfaction.
PMID- 24352397
TI - Evaluation of the vertical alterations of the upper second molars after the
alignment and leveling phase using the MBT technique.
AB - OBJECTIVE: This study aimed at comparing the distocervical angulations of upper
second molars crowns of groups with normal occlusion and with Angle Classes I and
II malocclusions. Additionally, it aimed to analyze the changes occurring after
alignment and leveling performed with MBT technique. METHODS: The sample of
normal occlusions comprised 32 lateral teleradiographs, while the sample of
malocclusions comprised 38 initial and post-leveling lateral teleradiographs.
RESULTS: The results did not show statistically significant differences between
morphological characteristics of the normal occlusion group and the malocclusion
group. On the other hand, after alignment and leveling, statistically significant
reduction was observed in distocervical inclinations with extrusion of the distal
portion of upper second molars.
PMID- 24352398
TI - Influence of treatment including second molars on final and postretention molar
angulation.
AB - OBJECTIVE: Evaluate axial mesiodistal inclinations of the mandibular molars in
orthodontically treated cases, analyzing whether inclusion of second mandibular
molars in treatment mechanics has any influence on final and postretention molars
angulations. METHODS: The sample comprised 150 panoramic radiographs of 50
patients. Patients were treated with extraction of four first premolars and
divided into 2 groups: Group 1 comprised 25 subjects without inclusion of
mandibular second molars during orthodontic treatment, whereas Group 2 comprised
25 subjects with inclusion of mandibular second molars. Panoramic radiographs at
three observation times were evaluated: pretreatment, posttreatment and
postretention. The statistical analysis included one-way analysis of variance
(ANOVA) for intragroup evaluation and independent t-tests for intergroup
comparisons. RESULTS: Intragroup analysis demonstrated significant uprighting of
mandibular first and second molars during treatment in Group 2, which remained
stable during the postretention stage. Intergroup comparison demonstrated that
Group 2 presented first and second molars significantly more uprighted in
relation to Group 1 in both post-treatment and postretention stages. CONCLUSIONS:
It was concluded that inclusion of mandibular second molars in the orthodontic
mechanics is relevant not only to correct the angulation of these teeth, but also
to aid mandibular first molars uprighting.
PMID- 24352399
TI - Intra-articular injections with corticosteroids and sodium hyaluronate for
treating temporomandibular joint disorders: a systematic review.
AB - INTRODUCTION: In some cases, conservative treatment of internal derangements of
the Temporomandibular Joint (TMJ) is considered little responsive. Thus, it is
necessary to accomplish treatments that aim at reducing pain and improve function
in patients who present arthrogenic temporomandibular disorders. OBJECTIVE: This
study, by means of a systematic review of the literature, aimed to analyze the
effectiveness of intra-articular injections with corticosteroids and sodium
hyaluronate for treating internal derangements of the TMJ. METHODS: Carry out a
research in the following databases: MEDLINE, Cochrane, EMBASE, Pubmed, Lilacs,
and BBO, considering publications issued between 1966 and October 2010, focusing
on randomized or quasi-randomized controlled clinical trials, single or double
blind. RESULTS: After applying the inclusion criteria we collected 9 articles, 7
of which were randomized controlled double-blind clinical trials and 2 randomized
controlled single-blind clinical trials. CONCLUSION: After analyzing the
literature, it was found that intra-articular injection with corticosteroids and
sodium hyaluronate seems to be an effective method for treating internal
derangements of the TMJ. However, further randomized controlled clinical trials,
with representative samples and longer follow-up time must be carried out in
order to assess the real effectiveness of this technique.
PMID- 24352400
TI - Therapeutic exercises for the control of temporomandibular disorders.
AB - INTRODUCTION: Temporomandibular disorder (TMD) is a multifactorial disease. For
this reason, it is difficult to obtain an accurate and correct diagnosis. In this
context, conservative treatments, including therapeutic exercises classified as
stretching, relaxation, coordination, strengthening and endurance, are oftentimes
prescribed. OBJECTIVE: Thus, the aim of the present article was to conduct a
literature review concerning the types of exercises available and the efficacy
for the treatment of muscular TMD. METHODS: The review included researches
carried out between 2000 and 2010, indexed on Web of Science, PubMed, LILACS and
BBO. Moreover, the following keywords were used: Exercise, physical therapy,
facial pain, myofascial pain syndrome, and temporomandibular joint dysfunction
syndrome. Studies that did not consider the subject "TMD and exercises", used
post-surgery exercises and did not use validated criteria for the diagnosis of
TMD (RDC/TMD) were not included. RESULTS: The results comprised seven articles
which proved therapeutic exercises to be effective for the treatment of muscular
TMD. However, these studies are seen as limited, since therapeutic exercises were
not applied alone, but in association with other conservative procedures. In
addition, they present some drawbacks such as: Small samples, lack of control
group and no detailed exercise description which should have included intensity,
repetition, frequency and duration. CONCLUSION: Although therapeutic exercises
are considered effective in the management of muscular TMD, the development of
randomized clinical trials is necessary, since many existing studies are still
based on the clinical experience of professionals.
PMID- 24352401
TI - Compensatory orthodontic treatment of Angle Class II malocclusion with posterior
open bite.
AB - The present case report addresses the treatment of an Angle Class II malocclusion
in an adult female patient, long face pattern, with posterior open bite and
dental arches extremely expanded, due to previous treatment. The patient and
parents rejection to a treatment with orthognathic surgery led to orthodontic
camouflage of the skeletal discrepancies. This clinical case was presented to the
Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as one of the
requirements to become a BBO Diplomate.
PMID- 24352402
TI - Finishing procedures in orthodontics: dental dimensions and proportions
(microesthetics).
AB - OBJECTIVE: The objective of the present article is to describe procedures that
can be performed to achieve excellence in orthodontic treatment finishing. The
content is limited to microesthetics, which comprises the concept of ideal dental
dimensions and proportions (white esthetics) and its correlation with the
periodontium (pink esthetics). Standards of normality are described both in their
real dimensions (dental height and width), and in those effectively perceived by
the observer, the virtual dimensions. METHODS: The best scientific evidence was
sought in the literature to support the clinical procedures that must guide the
professional to obtain maximum esthetic quality on their treatments. Therefore,
it is necessary to investigate what the other specialties in Dentistry expect
from Orthodontics and, specially, what they have to offer. Clinical cases will be
used to illustrate the dental movement that might maximize treatment outcome and
to confront the ideal standards with the current state of the art. CONCLUSION:
Treatment quality is directly related to the amount of procedures implemented by
the orthodontist, associated with concepts and resources from Periodontics and
Dental Prosthesis. Microesthetics cannot be seen in isolation, but rather as the
key to establish a pleasant smile (miniesthetics) in addition to a harmonious
face (macroesthetics) and a human being with high self-esteem (hyper-esthetics).
PMID- 24352404
TI - Editor's letter.
PMID- 24352403
TI - Long-term results of intensified, N-terminal-pro-B-type natriuretic peptide
guided versus symptom-guided treatment in elderly patients with heart failure:
five-year follow-up from TIME-CHF.
AB - BACKGROUND: Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT
proBNP) levels may improve outcomes in patients with chronic heart failure (HF),
especially in younger patients with reduced left ventricular ejection fraction.
It remains unclear whether treatment effects persist after discontinuation of the
NT-proBNP-guided treatment strategy. METHODS AND RESULTS: Trial of Intensified
versus standard Medical therapy in Elderly patients with Congestive Heart Failure
randomized 499 patients with HF aged>=60 years with left ventricular ejection
fraction<=45% to intensified, NT-proBNP-guided versus standard, symptom-guided
therapy into prespecified age groups (60-74 and >=75 years) during 18 months. A
total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF
medication was intensified to a larger extent in the NT-proBNP-guided group.
During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary
end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or
overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25)
but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95%
confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had
benefit from NT-proBNP-guided therapy on the primary end point and HF
hospitalization-free survival, whereas patients aged>=75 years did not (P<0.10
for interaction). In landmark analysis, there was no regression to the mean after
cessation of the NT-proBNP-guided strategy. More intensified HF medication at
month 12 was associated with better long-term HF hospitalization-free and overall
survival. CONCLUSIONS: Intensified, NT-proBNP-guided therapy did not improve the
primary end point compared with symptom-guided therapy but did improve HF
hospitalization-free survival. Within the subgroup of patients aged 60 to 74
years, it improved clinical outcome including the primary end point. These
effects did not disappear after cessation of the NT-proBNP-guided strategy on the
long-term. This is possibly attributable to a more intensified HF medical therapy
in the NT-proBNP-guided group. CLINICAL TRIAL REGISTRATION: URL:
http://www.isrctn.org. Unique identifier: ISRCTN43596477.
PMID- 24352405
TI - Cognitive and academic functioning of juvenile detainees: implications for
correctional populations and public health.
AB - Cognitive functioning affects health. This study assessed cognitive functioning
among participants in the Northwestern Juvenile Project, a stratified random
sample of 1,829 newly detained juveniles (10 to 18 years old) from Cook County,
Illinois. The study examined receptive vocabulary, oral reading, arithmetic
computation skills, and general intellectual abilities. The sample exhibited
impaired overall intellectual functioning and deficits in all areas. Males
performed more poorly than females. More than three quarters of males showed
below average overall intellectual functioning, and 9 in 10 had below average
receptive vocabulary skills. Hispanic and African American males performed more
poorly than non-Hispanic White males. The multiple systems that serve delinquent
youth--correctional, health, legal, and rehabilitative--must collaborate to
tailor needed services to the cognitive level of youth in the juvenile justice
system.
PMID- 24352406
TI - Voluntary STD testing and treatment program at a metropolitan correctional
facility: evaluation of test acceptability and associated risk factors.
AB - Few studies have addressed challenges of diagnosis and treatment of sexually
transmitted diseases (STDs) within correctional facilities. Initiatives that
screen all inmates can be cost-prohibitive, while symptom-based screening
undoubtedly fails to recognize significant numbers of asymptomatically infected
persons. This study discusses a voluntary STD screening and treatment program
developed at the Douglas County (Nebraska) Department of Corrections where
student volunteers interviewed, screened, and educated 456 inmates. Inmate urine
samples and interview responses about risk behaviors and motivators for
participation in the screening program were analyzed. The results support the
ongoing project method to screen and treat inmates in the community correctional
facility. Risk factor analysis suggests that targeted testing and treatment
efforts may have a role in providing cost-effective care for STD among the
incarcerated population.
PMID- 24352408
TI - [Choosing Wisely. A model for the German health care system?].
AB - BACKGROUND: In 2011 the American Board of Internal Medicine (ABIM) started the
Choosing Wisely campaign. MATERIALS AND METHODS: The goal was to establish top 5
lists by the medical societies to reduce diagnostic and therapeutic procedures
which are not necessary or are potentially harmful, and thereby lower health care
costs. The lists contributed by the American Geriatric Society and the American
Medical Director Association in 2013 will be discussed. CONCLUSION: At first
glance, the idea seems simple, but numerous questions remain. Transferring this
process to Germany appears theoretically possible, but various aspects of the
health care system should be taken into consideration.
PMID- 24352409
TI - Diurnal rodents as an advantageous model for affective disorders: novel data from
diurnal degu (Octodon degus).
AB - Circadian rhythms are strongly associated with affective disorders and recent
studies have suggested utilization of diurnal rodents as model animal for
circadian rhythms-related domains of these disorders. Previous work with the
diurnal fat sand rat and Nile grass rat demonstrated that short photoperiod
conditions result in behavioral changes including anxiety- and depression-like
behavior. The present study examined the effect of manipulating day length on
activity rhythms and behavior of the diurnal degu. Animals were housed for 3
weeks under either a short photoperiod (5-h:19-h LD) or a neutral photoperiod (12
h:12-h LD) and then evaluated by sweet solution test and the forced swim test for
depression-like behavior, and in the light/dark box and open field for anxiety
like behavior. Results indicate that short photoperiod induced depression-like
behavior in the forced swim test and the sweet solution preference test and
anxiety-like behavior in the open field compared with animals maintained in a
neutral photoperiod. No effects were shown in the light/dark box. Short
photoperiod-acclimated degu showed reduced total activity duration and activity
was not restricted to the light phase. The present study further supports the
utilization of diurnal rodents to model circadian rhythms-related affective
change. Beyond the possible diversity in the mechanisms underlying diurnality in
different animals, there are now evidences that in three different diurnal
species, the fat sand rat, the grass Nile rat and the degu, shortening of
photoperiod results in the appearance of anxiety- and depression-like behaviors.
PMID- 24352410
TI - Intraduodenal milk protein concentrate augments the glycemic and food intake
suppressive effects of DPP-IV inhibition.
AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L
cells in response to food entering into the gastrointestinal tract. GLP-1-based
pharmaceuticals improve blood glucose regulation and may hold promise for obesity
treatment, as GLP-1 drugs reduce food intake and body weight in humans and
animals. In an effort to improve GLP-1 pharmacotherapies, we focused our
attention on macronutrients that, when present in the gastrointestinal tract, may
enhance GLP-1 secretion and improve glycemic regulation and food intake
suppression when combined with systemic administration of sitagliptin, a
pharmacological inhibitor of DPP-IV (enzyme responsible for GLP-1 degradation).
In particular, previous data suggest that specific macronutrient constituents
found in dairy foods may act as potent secretagogues for GLP-1 and therefore may
potentially serve as an adjunct dietary therapy in combination with sitagliptin.
To directly test this hypothesis, rats received intraperitoneal injections of
sitagliptin (6 mg/kg) or saline vehicle followed by intraduodenal infusions of
either milk protein concentrate (MPC; 80/20% casein/whey; 4 kcal), soy protein
(nondairy control infusate; 4 kcal), or 0.9% NaCl. Food intake was assessed 30
min postinfusion. In separate studies, regulation of blood glucose was examined
via a 2-h oral glucose tolerance test (2 g/kg) following identical sitagliptin
treatment and intraduodenal nutrient infusions. Collectively, results show that
intraduodenal MPC, but not soy protein, significantly enhances both the food
intake suppression and improved control of blood glucose produced by sitagliptin.
These data support the hypothesis that dietary intake of dairy protein may be
beneficial as an adjunct behavioral therapy to enhance the glycemic and food
intake suppressive effects of GLP-1-based pharmacotherapies.
PMID- 24352412
TI - ISCB: past-present perspective for the International Society for Computational
Biology.
AB - Since its establishment in 1997, International Society for Computational Biology
(ISCB) has contributed importantly toward advancing the understanding of living
systems through computation. The ISCB represents nearly 3000 members working in
>70 countries. It has doubled the number of members since 2007. At the same time,
the number of meetings organized by the ISCB has increased from two in 2007 to
eight in 2013, and the society has cemented many lasting alliances with regional
societies and specialist groups. ISCB is ready to grow into a challenging and
promising future. The progress over the past 7 years has resulted from the
vision, and possibly more importantly, the passion and hard working dedication of
many individuals.
PMID- 24352411
TI - Differential regulation of TRPC4 in the vasopressin magnocellular system by water
deprivation and hepatic cirrhosis in the rat.
AB - Transient receptor potential canonical subtype 4 (TRPC4) is expressed in the
magnocellular paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the
hypothalamus. In this study, the regulation of TRPC4 expression was investigated
in water deprivation and hepatic cirrhosis. We used laser capture microdissection
technique for precise dissection of pure AVP cell population in the PVN and SON
followed by quantitative real-time RT-PCR, and immunodetection techniques by
Western blot analysis and immunofluorescence. Bile duct ligation elevated TRPC4
transcripts in the SON but not PVN with correlated changes in the protein
expression in these regions, as well as increased colocalization with AVP in the
SON, with no changes in the PVN. Water deprivation resulted in increased TRPC4
mRNA expression in the PVN, while it decreased channel expression levels in the
SON. In both of these regions, protein expression measured from tissue punches
were unaltered following water deprivation, with no changes in the number of
TRPC4-positive cells. Thus, TRPC4 expression is differentially regulated in
physiological and pathophysiological models of vasopressin release.
PMID- 24352414
TI - RCT of working memory training in ADHD: long-term near-transfer effects.
AB - OBJECTIVE: The aim of the study is to evaluate the long-term near-transfer
effects of computerized working memory (WM) training on standard WM tasks in
children with Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD: Sixty
seven children aged 10-12 years in Vestfold/Telemark counties (Norway) diagnosed
with F90.0 Hyperkinetic disorder (ICD-10) were randomly assigned to training or
control group. The training group participated in a 25-day training program at
school, while the control group received treatment-as-usual. Participants were
tested one week before intervention, immediately after and eight months later.
Based on a component analysis, six measures of WM were grouped into composites
representing Visual, Auditory and Manipulation WM. RESULTS: The training group
had significant long-term differential gains compared to the control group on all
outcome measures. Performance gains for the training group were significantly
higher in the visual domain than in the auditory domain. The differential gain in
Manipulation WM persisted after controlling for an increase in simple storage
capacity. CONCLUSION: Systematic training resulted in a long-term positive gain
in performance on similar tasks, indicating the viability of training
interventions for children with ADHD. The results provide evidence for both
domain-general and domain-specific models. Far-transfer effects were not
investigated in this article. TRIAL REGISTRATION: Controlled-Trials.com
ISRCTN19133620.
PMID- 24352415
TI - Sex differences in the protection of host immune systems by a polyembryonic
parasitoid.
AB - Endoparasitoids have the ability to evade the cellular immune responses of a host
and to create an environment suitable for survival of their progeny within a
host. Generally, the host immune system is suppressed by endoparasitoids.
However, polyembryonic endoparasitoids appear to invade their hosts using
molecular mimicry rather than immune system suppression. It is not known how the
host immune system is modified by polyembryonic endoparasitoids. Using haemocyte
counts and measurement of cellular immune responses, we evaluated modification of
the host immune system after separate infestations by a polyembryonic parasitoid
(Copidosoma floridanum) and another parasitoid (Glyptapanteles pallipes) and by
both together (multi-parasitism). We found that the polyembryonic parasitoid
maintains and enhances the host immune system, whereas the other parasitoid
strongly suppresses the immune system. Multi-parasitization analysis revealed
that C. floridanum cancelled the immune suppression by G. pallipes and
strengthened the host immunity. This enhancement was much stronger with male than
with female C. floridanum.
PMID- 24352416
TI - Maternal antibodies contribute to sex-based difference in hantavirus transmission
dynamics.
AB - Individuals often differ in their ability to transmit disease and identifying key
individuals for transmission is a major issue in epidemiology. Male hosts are
often thought to be more important than females for parasite transmission and
persistence. However, the role of infectious females, particularly the transient
immunity provided to offspring through maternal antibodies (MatAbs), has been
neglected in discussions about sex-biased infection transmission. We examined the
effect of host sex upon infection dynamics of zoonotic Puumala hantavirus (PUUV)
in semi-natural, experimental populations of bank vole (Myodes glareolus).
Populations were founded with either females or males that were infected with
PUUV, whereas the other sex was immunized against PUUV infection. The likelihood
of the next generation being infected was lower when the infected founders were
females, underlying the putative importance of adult males in PUUV transmission
and persistence in host populations. However, we show that this effect probably
results from transient immunity that infected females provide to their offspring,
rather than any sex-biased transmission efficiency per se. Our study proposes a
potential contrasting nature of female and male hosts in the transmission
dynamics of hantaviruses.
PMID- 24352417
TI - Controlled type II diabetes mellitus has no major influence on platelet micro-RNA
expression. Results from micro-array profiling in a cohort of 60 patients.
AB - Diabetes mellitus as a major contributor to cardiovascular disease burden induces
dysfunctional platelets. Platelets contain abundant miRNAs, which are linked to
inflammatory responses and, thus, may play a role in atherogenesis. While
diabetes mellitus affects plasma miRNAs, no data exist on platelet miRNA profiles
in this disease. Therefore, this study sought to explore the miRNA profile of
platelets in patients with diabetes mellitus that is unrelated to the presence or
absence of coronary artery disease (CAD). Platelet miRNA profiles were assessed
in stable diabetic and non-diabetic patients (each n=30); 15 patients in each
group had CAD. Platelet miRNA was isolated from leucocyte-depleted platelet-rich
plasma, and miRNA profiling was performed using LNA micro-array technology
(miRBase18.0, containing 1,917 human miRNAs). Effects of diabetes mellitus were
explored by univariate statistical tests for each miRNA, adjusted for potential
confounders, and by developing a multivariable signature; evaluated by resampling
techniques. Platelets in non-diabetic patients demonstrated miRNA expression
profiles comparable to previous data. The miRNA profiles of platelets in
diabetics were similar. Statistical analysis unveiled three miRNAs (miR-377-5p,
miR-628-3p, miR-3137) with high reselection probabilities in resampling
techniques, corresponding to signatures with modest discriminatory performance.
Functional annotation of predicted targets for these miRNAs pointed towards an
influence of diabetes mellitus on mRNA processing. We did not find major
differences in platelet miRNA profiles between diabetics and non-diabetics. Minor
differences pertained to miRNAs associated with mRNA processing. Thus, described
differences in plasma miRNAs between diabetic and non-diabetic patients cannot be
explained by plain changes in platelet miRNA profile.
PMID- 24352418
TI - Can crude oil toxicity on phytoplankton be predicted based on toxicity data on
benzo(a)pyrene and naphthalene?
AB - Polycyclic aromatic hydrocarbons (PAHs), which are major components of crude oil,
are responsible in large part for the toxicity of crude oil to phytoplankton.
This study addressed the following question. Can reliable predictions of the
aquatic toxicity of crude oil, a multi-component mixture, be described from
toxicity data on individual PAH compounds? Naphthalene, the most abundant PAH
compound, and benzo(a)pyrene, a highly toxic PAH compound, were selected as model
compounds to quantify toxicity of crude oil on two phytoplankton species, Ditylum
brightwellii and Heterocapsa triquetra, by analyzing the effects of different
concentrations of these PAHs on growth rate. EC50 values suggested that the
diatom D. brightwellii was more vulnerable to both toxicants than the
dinoflagellate H. triquetra. However, a previous study, which investigated the
impact of crude oil on the same two species, had opposite results. The
differences in response from these phytoplankton species to naphthalene and
benzo(a)pyrene toxicity compared to their response to crude oil suggest that they
may not be solely used as surrogates to assess crude oil toxicity on
phytoplankton.
PMID- 24352419
TI - Hallmarks of a new era in mitochondrial biochemistry.
AB - Stemming from the pioneering studies of bioenergetics in the 1950s, 1960s, and
1970s, mitochondria have become ingrained in the collective psyche of scientists
as the "powerhouses" of the cell. While this remains a worthy moniker, more
recent efforts have revealed that these organelles are home to a vast array of
metabolic and signaling processes and possess a proteomic landscape that is both
highly varied and largely uncharted. As mitochondrial dysfunction is increasingly
being implicated in a spectrum of human diseases, it is imperative that we
construct a more complete framework of these organelles by systematically
defining the functions of their component parts. Powerful new approaches in
biochemistry and systems biology are helping to fill in the gaps.
PMID- 24352420
TI - The role of disordered protein regions in the assembly of decapping complexes and
RNP granules.
AB - The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits
translation and generally commits the mRNA to irreversible 5'-to-3'
exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by
DCP1, and these proteins form the conserved core of the decapping complex.
Additional decapping factors orchestrate the recruitment and activity of this
complex in vivo. These factors include enhancer of decapping 3 (EDC3), EDC4, like
Sm14A (LSm14A), Pat, the LSm1-7 complex, and the RNA helicase DDX6. Decapping
factors are often modular and feature folded domains flanked or connected by low
complexity disordered regions. Recent studies have made important advances in
understanding how these disordered regions contribute to the assembly of
decapping complexes and promote phase transitions that drive RNP granule
formation. These studies have also revealed that the decapping network is
governed by interactions mediated by short linear motifs (SLiMs) in these
disordered regions. Consequently, the network has rapidly evolved, and although
decapping factors are conserved, individual interactions between orthologs have
been rewired during evolution. The plasticity of the network facilitates the
acquisition of additional subunits or domains in pre-existing subunits, enhances
opportunities for regulating mRNA degradation, and eventually leads to the
emergence of novel functions.
PMID- 24352421
TI - Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem
cells in a noncanonical Notch signaling pathway.
AB - The self-renewal versus differentiation choice of Drosophila and mammalian neural
stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is
not well understood. Here we show that canonical N signaling cooperates with a
noncanonical N signaling pathway to mediate N-directed NSC regulation. In the
noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence
mitochondrial function, activating mechanistic target of rapamycin complex 2
(mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling
preferentially impaired the maintenance of Drosophila and human cancer stem cell
like tumor-forming cells. Our results emphasize the importance of mitochondria to
N and NSC biology, with important implications for diseases associated with
aberrant N signaling.
PMID- 24352422
TI - Nucleosome-binding activities within JARID2 and EZH1 regulate the function of
PRC2 on chromatin.
AB - Polycomb-repressive complex 2 (PRC2) comprises specific members of the Polycomb
group of epigenetic modulators. PRC2 catalyzes methylation of histone H3 at Lys
27 (H3K27me3) through its Enhancer of zeste (Ezh) constituent, of which there are
two mammalian homologs: Ezh1 and Ezh2. Several ancillary factors, including
Jarid2, modulate PRC2 function, with Jarid2 facilitating its recruitment to
target genes. Jarid2, like Ezh2, is present in poorly differentiated and actively
dividing cells, while Ezh1 associates with PRC2 in all cells, including resting
cells. We found that Jarid2 exhibits nucleosome-binding activity that contributes
to PRC2 stimulation. Moreover, such nucleosome-binding activity is exhibited by
PRC2 comprising Ezh1 (PRC2-Ezh1), in contrast to PRC2-Ezh2. The presence of Ezh1
helps to maintain PRC2 occupancy on its target genes in myoblasts where Jarid2 is
not expressed. Our findings allow us to propose a model in which PRC2-Ezh2 is
important for the de novo establishment of H3K27me3 in dividing cells, whereas
PRC2-Ezh1 is required for its maintenance in resting cells.
PMID- 24352423
TI - Multiple small RNA pathways regulate the silencing of repeated and foreign genes
in C. elegans.
AB - Gene segments from other organisms, such as viruses, are detected as foreign and
targeted for silencing by RNAi pathways. A deep-sequencing map of the small RNA
response to repeated transgenes introduced to Caenorhabditis elegans revealed
that specific segments are targeted by siRNAs. Silencing of the foreign gene
segments depends on an antiviral response that involves changes in active and
silent chromatin modifications and altered levels of antisense siRNAs. Distinct
Argonaute proteins target foreign genes for silencing or protection against
silencing. We used a repeated transgene in a genome-wide screen to identify gene
disruptions that enhance silencing of foreign genetic elements and identified 69
genes. These genes cluster in four groups based on overlapping sets of
coexpressed genes, including a group of germline-expressed genes that are likely
coregulated by the E2F transcription factor. Many of the gene inactivations
enhance exogenous RNAi. About half of the 69 genes have roles in endogenous RNAi
pathways that regulate diverse processes, including silencing of duplicated genes
and transposons and chromosome segregation. Of these newly identified genes,
several are required for siRNA biogenesis or stability in the oocyte-specific
ERGO-1 pathway, including eri-12, encoding an interactor of the RNAi-defective
protein RDE-10, and ntl-9/CNOT9, one of several CCR4/NOT complex genes that we
identified. The conserved ARF-like small GTPase ARL-8 is required specifically
for primary siRNA biogenesis or stability in the sperm-specific ALG-3/4
endogenous RNAi pathway.
PMID- 24352424
TI - eIF2B promotes eIF5 dissociation from eIF2*GDP to facilitate guanine nucleotide
exchange for translation initiation.
AB - Protein synthesis factor eIF2 delivers initiator tRNA to the ribosome. Two
proteins regulate its G-protein cycle: eIF5 has both GTPase-accelerating protein
(GAP) and GDP dissociation inhibitor (GDI) functions, and eIF2B is the guanine
nucleotide exchange factor (GEF). In this study, we used protein-protein
interaction and nucleotide exchange assays to monitor the kinetics of eIF2
release from the eIF2*GDP/eIF5 GDI complex and determine the effect of eIF2B on
this release. We demonstrate that eIF2B has a second activity as a GDI
displacement factor (GDF) that can recruit eIF2 from the eIF2*GDP/eIF5 GDI
complex prior to GEF action. We found that GDF function is dependent on the
eIF2Bepsilon and eIF2Bgamma subunits and identified a novel eIF2-eIF2Bgamma
interaction. Furthermore, GDF and GEF activities are shown to be independent.
First, eIF2B GDF is insensitive to eIF2alpha phosphorylation, unlike GEF. Second,
we found that eIF2Bgamma mutations known to disrupt GCN4 translational control
significantly impair GDF activity but not GEF function. Our data therefore define
an additional step in the protein synthesis initiation pathway that is important
for its proper control. We propose a new model to place eIF2B GDF function in the
context of efficient eIF2 recycling and its regulation by eIF2 phosphorylation.
PMID- 24352425
TI - Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in
neocortical progenitor cells.
AB - Down's syndrome (DS), a major genetic cause of mental retardation, arises from
triplication of genes on human chromosome 21. Here we show that DYRK1A (dual
specificity tyrosine-phosphorylated and -regulated kinase 1A) and DSCR1 (DS
critical region 1), two genes lying within human chromosome 21 and encoding for a
serine/threonine kinase and calcineurin regulator, respectively, are expressed in
neural progenitors in the mouse developing neocortex. Increasing the dosage of
both proteins in neural progenitors leads to a delay in neuronal differentiation,
resulting ultimately in alteration of their laminar fate. This defect is mediated
by the cooperative actions of DYRK1A and DSCR1 in suppressing the activity of the
transcription factor NFATc. In Ts1Cje mice, a DS mouse model, dysregulation of
NFATc in conjunction with increased levels of DYRK1A and DSCR1 was observed.
Furthermore, counteracting the dysregulated pathway ameliorates the delayed
neuronal differentiation observed in Ts1Cje mice. In sum, our findings suggest
that dosage of DYRK1A and DSCR1 is critical for proper neurogenesis through NFATc
and provide a potential mechanism to explain the neurodevelopmental defects in
DS.
PMID- 24352426
TI - Anti-adaptors provide multiple modes for regulation of the RssB adaptor protein.
AB - RpoS, an RNA polymerase sigma factor, controls the response of Escherichia coli
and related bacteria to multiple stress responses. During nonstress conditions,
RpoS is rapidly degraded by ClpXP, mediated by the adaptor protein RssB, a member
of the response regulator family. In response to stress, RpoS degradation ceases.
Small anti-adaptor proteins--IraP, IraM, and IraD, each made under a different
stress condition--block RpoS degradation. RssB mutants resistant to either IraP
or IraM were isolated and analyzed in vivo and in vitro. Each of the anti
adaptors is unique in its interaction with RssB and sensitivity to RssB mutants.
One class of mutants defined an RssB N-terminal region close to the
phosphorylation site and critical for interaction with IraP but unnecessary for
IraM and IraD function. A second class, in the RssB C-terminal PP2C-like domain,
led to activation of RssB function. These mutants allowed the response regulator
to act in the absence of phosphorylation but did not abolish interaction with
anti-adaptors. This class of mutants is broadly resistant to the anti-adaptors
and bears similarity to constitutively activated mutants found in a very
different PP2C protein. The mutants provide insight into how the anti-adaptors
perturb RssB response regulator function and activation.
PMID- 24352430
TI - Ion-selective gold-thiol film on integrated screen-printed electrodes for
analysis of Cu(II) ions.
AB - A novel type of ion-selective electrode (ISE) was manufactured for detecting
trace amounts of Cu(II) ions. The basic substrates of ISE were fabricated using
screen-printing technology, which could produce disposable electrodes on a large
scale with good repeatability. Moreover, the printed integrated three-electrode
system of ISE could be directly used to read out the open-circuit potentials by a
handheld device through a USB port. The ion-selective film was composed of gold
nanorods (GNRs) and 6-(bis(pyridin-2-ylmethyl)amino)hexane-1-thiol (compound ),
which were layer-by-layer modified on the electrode through an easily controlled
self-assembly method. Compound contained the 2,2'-dipyridylamine (dpa) group that
could coordinate with Cu(II) ions to form a 2 : 1 complex, therefore the screen
printed ISEs exhibited Nernstian potentiometric responses to Cu(II) ions with a
detection limit of 6.3 * 10(-7) mol L(-1) over the range of 1.0 * 10(-6) to 1.0 *
10(-2) mol L(-1). The easily prepared screen-printed ion-selective electrode
reported here was appropriate for in field analysis and pollutant detection in
remote environments.
PMID- 24352427
TI - Inferring the choreography of parental genomes during fertilization from
ultralarge-scale whole-transcriptome analysis.
AB - Fertilization precisely choreographs parental genomes by using gamete-derived
cellular factors and activating genome regulatory programs. However, the
mechanism remains elusive owing to the technical difficulties of preparing large
numbers of high-quality preimplantation cells. Here, we collected >14 * 10(4)
high-quality mouse metaphase II oocytes and used these to establish detailed
transcriptional profiles for four early embryo stages and parthenogenetic
development. By combining these profiles with other public resources, we found
evidence that gene silencing appeared to be mediated in part by noncoding RNAs
and that this was a prerequisite for post-fertilization development. Notably, we
identified 817 genes that were differentially expressed in embryos after
fertilization compared with parthenotes. The regulation of these genes was
distinctly different from those expressed in parthenotes, suggesting functional
specialization of particular transcription factors prior to first cell cleavage.
We identified five transcription factors that were potentially necessary for
developmental progression: Foxd1, Nkx2-5, Sox18, Myod1, and Runx1. Our very large
scale whole-transcriptome profile of early mouse embryos yielded a novel and
valuable resource for studies in developmental biology and stem cell research.
The database is available at http://dbtmee.hgc.jp.
PMID- 24352431
TI - Elevated plasma inflammatory markers in individuals with intermittent explosive
disorder and correlation with aggression in humans.
AB - IMPORTANCE: Neurochemical studies in human aggression point to a modulatory role
for a variety of central neurotransmitters. Some of these neurotransmitters play
an inhibitory role, while others play a facilitatory role modulating aggression.
Preclinical studies suggest a facilitatory role for inflammatory markers in
aggression. Despite this, to our knowledge, no studies of aggression and
inflammatory markers have been reported in psychiatric patients or in individuals
with recurrent, problematic, impulsive aggressive behavior. OBJECTIVE: To test
the hypothesis that plasma inflammatory markers will correlate directly with
aggression and will be elevated in individuals with recurrent, problematic,
impulsive aggressive behavior. DESIGN, SETTING, AND PARTICIPANTS Case-control
study in a clinical research program in impulsive aggressive behavior at an
academic medical center. Participants were physically healthy individuals with
intermittent explosive disorder (n = 69), nonaggressive individuals with Axis I
and/or II disorders (n = 61), and nonaggressive individuals without history of an
Axis I or II disorder (n = 67). MAIN OUTCOMES AND MEASURES: Plasma levels of C
reactive protein and interleukin 6 were examined in the context of measures of
aggression and impulsivity and as a function of intermittent explosive disorder.
RESULTS: Both plasma C-reactive protein and interleukin 6 levels were
significantly higher in participants with intermittent explosive disorder
compared with psychiatric or normal controls. In addition, both inflammatory
markers were directly correlated with a composite measure of aggression and, more
specifically, with measures reflecting history of actual aggressive behavior in
all participants. CONCLUSIONS AND RELEVANCE: These data suggest a direct
relationship between plasma inflammatory processes and aggression in humans. This
finding adds to the complex picture of the central neuromodulatory role of
aggression in humans.
PMID- 24352432
TI - Oxidative stress response of Blakeslea trispora induced by H2O2 during beta
carotene biosynthesis.
AB - The cellular response of Blakeslea trispora to oxidative stress induced by H2O2
in shake flask culture was investigated in this study. A mild oxidative stress
was created by adding 40 MUm of H2O2 into the medium after 3 days of the
fermentation. The production of beta-carotene increased nearly 38 % after a 6-day
culture. Under the oxidative stress induced by H2O2, the expressions of hmgr,
ipi, carG, carRA, and carB involving the beta-carotene biosynthetic pathway all
increased in 3 h. The aerobic metabolism of glucose remarkably accelerated within
24 h. In addition, the specific activities of superoxide dismutase and catalase
were significantly increased. These changes of B. trispora were responses for
reducing cell injury, and the reasons for increasing beta-carotene production
caused by H2O2.
PMID- 24352433
TI - Indoleamides are active against drug-resistant Mycobacterium tuberculosis.
AB - Responsible for nearly two million deaths each year, the infectious disease
tuberculosis remains a serious global health challenge. The emergence of
multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis
confounds control efforts, and new drugs with novel molecular targets are
desperately needed. Here we describe lead compounds, the indoleamides, with
potent activity against both drug-susceptible and drug-resistant strains of M.
tuberculosis by targeting the mycolic acid transporter MmpL3. We identify a
single mutation in mmpL3, which confers high resistance to the indoleamide class
while remaining susceptible to currently used first- and second-line tuberculosis
drugs, indicating a lack of cross-resistance. Importantly, an indoleamide
derivative exhibits dose-dependent antimycobacterial activity when orally
administered to M. tuberculosis-infected mice. The bioavailability of the
indoleamides, combined with their ability to kill tubercle bacilli, indicates
great potential for translational developments of this structure class for the
treatment of drug-resistant tuberculosis.
PMID- 24352434
TI - Molecular characterization of a rabies virus isolate from a rabid dog in Hanzhong
District, Shaanxi Province, China.
AB - A canine rabies virus, Shaanxi-HZ-6, was isolated in Shaanxi Province, China, in
2009. Its genome has been completely sequenced and found to be closely related to
the China I rabies virus strains widely circulating in China. The genomic length
was 11,923 base pairs, and the overall organization of the genome was similar to
that of other rabies virus isolates. Compared with isolates CQ92 and J, 84 amino
acid substitutions (7 in the N gene, 15 in P, 6 in M, 25 in G, 31 in L) were
observed in strain Shaanxi-HZ-6. Amino acid substitutions of R264H and V332I were
noted in the G protein antigenic site I and site III, respectively. Residue 333
of the G protein, which is considered to be associated with pathogenicity, was
Arg in Shaanxi-HZ-6. These and other substitutions may help provide an
explanation why the China I lineage strain maintains its prevalence in China.
PMID- 24352435
TI - Molecular detection and genetic analysis of porcine bocavirus in Korean domestic
swine herds.
AB - Several porcine bocaviruses have been detected worldwide, and this report is the
first to describe this virus in a Korean domestic swine herd. We identified
porcine bocavirus in various samples, including serum, tissue, feces and saliva,
which revealed that porcine bocavirus predominates in Korean domestic swine
populations. The results of this study also suggested that porcine bocaviruses
primarily infect weaned piglets. Phylogenetic analysis of the ORF3 gene was
performed to determine the genetic relationship of the Korean strains to
reference strains from other countries.
PMID- 24352436
TI - Equine herpesvirus type 1 (EHV-1)-induced rearrangements of actin filaments in
productively infected primary murine neurons.
AB - Equine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion and
neurological disorders in horses. In the present study, we investigated
reorganization of the cytoskeleton in neurons infected with two EHV-1 strains:
Jan-E (wild-type strain) and Rac-H (attenuated strain). The studies were
performed on primary murine neurons, which are an excellent model for studying
neurotropism and neurovirulence of EHV-1. We have demonstrated for the first time
that EHV-1 infection causes rearrangements in the actin network of neurons that
are dependent on the virus strain and its adaptation to cell culture in vitro.
Immunofluorescent labeling and confocal microscopy revealed the formation of
long, thin projections in neurons infected with the Jan-E strain, which was
probably associated with enhanced intracellular spread of the virus. The EHV-1
Rac-H strain caused disruption of the microfilaments system and general
depolymerization of actin, but treatment of neurons with cytochalasin D or
latrunculin A resulted in limitation of viral replication. It can therefore be
assumed that actin filaments are required only at the early stages of infection.
Our results allow us to suggest that the actin cytoskeleton participates in EHV-1
infection of primary murine neurons but is not essential, and that other
components of the cytoskeleton and/or cellular mechanisms may be also involved
during EHV-1 infection.
PMID- 24352437
TI - Genetic diversity of the coat protein of olive latent virus 1 isolates.
AB - The CP gene variability among 21 olive latent virus 1 (OLV-1) isolates obtained
from different hosts and locations and at different times was assessed. Amplicons
obtained by RT-PCR were cloned, and at least 10 sequences from each isolate were
analyzed and compared. OLV-1 sequences available in GenBank were included. The
encoded CPs consisted of 270 amino acids, except those of isolates G1S and C7
(269 aa) and G6 (271 aa). Comparison of CP genomic sequences of the isolates
under study showed very low values of nucleotide diversity, 0.02, and maximum
nucleotide distances between (0.087) or within isolates (0.001). Although very
few nucleotide sequence differences were observed among the isolates, olive
isolates exhibited lower diversity (0.012). In addition, at position 158 (157 in
C7 and G1S and 159 in G6) of the deduced aa sequences, an alanine residue was
found to be conserved among the olive isolates. In citrus and tulip isolates, a
threonine residue was present at position 158, whereas a valine was present at
this same position in tomato isolates. Phylogenetic analysis indicated that OLV-1
isolates clustered in five groups according to original host. However, G6,
originally recovered from olive but repeatedly inoculated and maintained in N.
benthamiana plants for 8 years in our laboratory, was separated from other
isolates. This may be attributable to adaptation to the experimental host over
time. There was no correlation of phylogenetic grouping of isolates based on
geographical location or year of collection. Strong negative selection may have
contributed to the low diversity among the OLV-1 CP isolates.
PMID- 24352438
TI - Respiratory syncytial virus infection, TLR3 ligands, and proinflammatory
cytokines induce CD161 ligand LLT1 expression on the respiratory epithelium.
AB - During respiratory-virus infection, excessive lymphocyte activation can cause
pathology both in acute infection and in exacerbations of chronic respiratory
diseases. The costimulatory molecule CD161 is expressed on lymphocyte subsets
implicated in promoting respiratory inflammation, including Th2, Th17, mucosally
associated invariant T (MAIT) cells, and type 2 innate lymphoid cells. We asked
whether the CD161 ligand LLT1 could be expressed on respiratory epithelial cells
following respiratory-virus infection as a mechanism by which respiratory-virus
infection could promote activation of proinflammatory lymphocytes. In response to
respiratory syncytial virus (RSV) infection, expression of LLT1 was upregulated
in the BEAS-2B respiratory epithelial cell line and primary human bronchial
epithelial cells. Imaging studies revealed that LLT1 expression increased in both
RSV-infected and cocultured uninfected cells, suggesting that soluble factors
produced during infection stimulate LLT1 expression. TLR3 and TLR2/6 ligands led
to a rapid increase in LLT1 mRNA in respiratory epithelial cells, as did the
proinflammatory cytokines type I interferons, interleukin 1beta (IL-1beta), and
tumor necrosis factor alpha (TNF-alpha), which are produced early in respiratory
virus infection. Immunohistochemistry confirmed the increase in LLT1 protein on
the epithelial cell surface, and live-cell confocal microscopy demonstrated
accumulation of epithelial LLT1 at synapses formed with CD161(+) T lymphocytes.
LLT1 expression by the respiratory epithelium in response to respiratory-virus
infection and inflammatory cytokines represents a novel link between innate
immunity and lymphocyte activation. As a regulator of CD161(+) proinflammatory
lymphocytes, LLT1 could be a novel therapeutic target in inflammation caused by
respiratory-virus infection. IMPORTANCE: The immune response to respiratory-virus
infection is essential for clearing the pathogen but, if excessive, can lead to
tissue damage and obstruction of the airways. How viral infection activates
immune cells in the lungs is not fully understood. Here, we show that LLT1 can be
expressed in lung cells in response to infection. LLT1 triggers CD161, a receptor
on inflammatory immune cells. This mechanism may promote activation of immune
cells in the lungs in viral infection and could be a novel target for therapies
aimed at reducing lung inflammation.
PMID- 24352439
TI - Large-scale production and structural and biophysical characterizations of the
human hepatitis B virus polymerase.
AB - Hepatitis B virus (HBV) is a major human pathogen that causes serious liver
disease and 600,000 deaths annually. Approved therapies for treating chronic HBV
infections usually target the multifunctional viral polymerase (hPOL).
Unfortunately, these therapies--broad-spectrum antivirals--are not general cures,
have side effects, and cause viral resistance. While hPOL remains an attractive
therapeutic target, it is notoriously difficult to express and purify in a
soluble form at yields appropriate for structural studies. Thus, no empirical
structural data exist for hPOL, and this impedes medicinal chemistry and rational
lead discovery efforts targeting HBV. Here, we present an efficient strategy to
overexpress recombinant hPOL domains in Escherichia coli, purifying them at high
yield and solving their known aggregation tendencies. This allowed us to perform
the first structural and biophysical characterizations of hPOL domains. Apo-hPOL
domains adopt mainly alpha-helical structures with small amounts of beta-sheet
structures. Our recombinant material exhibited metal-dependent, reverse
transcriptase activity in vitro, with metal binding modulating the hPOL
structure. Calcomine orange 2RS, a small molecule that inhibits duck HBV POL
activity, also inhibited the in vitro priming activity of recombinant hPOL. Our
work paves the way for structural and biophysical characterizations of hPOL and
should facilitate high-throughput lead discovery for HBV. IMPORTANCE: The viral
polymerase from human hepatitis B virus (hPOL) is a well-validated therapeutic
target. However, recombinant hPOL has a well-deserved reputation for being
extremely difficult to express in a soluble, active form in yields appropriate to
the structural studies that usually play an important role in drug discovery
programs. This has hindered the development of much-needed new antivirals for
HBV. However, we have solved this problem and report here procedures for
expressing recombinant hPOL domains in Escherichia coli and also methods for
purifying them in soluble forms that have activity in vitro. We also present the
first structural and biophysical characterizations of hPOL. Our work paves the
way for new insights into hPOL structure and function, which should assist the
discovery of novel antivirals for HBV.
PMID- 24352440
TI - Dispersed and conserved hydrophobic residues of HIV-1 Vif are essential for
CBFbeta recruitment and A3G suppression.
AB - CBFbeta was recently found to be a key regulator of the ability of human
immunodeficiency virus type 1 (HIV-1) Vif to overcome host antiviral APOBEC3
proteins. However, the detailed molecular requirements for the Vif-CBFbeta
interaction are still not clear. Here, we mapped the minimum Vif domain required
for CBFbeta binding. In terms of CBFbeta binding, the Vif N terminus was very
sensitive to deletions. We determined that the Vif fragment from residues 5 to
126 was sufficient to form a stable complex with CBFbeta in vitro. We also
observed that ionic interactions were not the main contributor to the interaction
between Vif and CBFbeta. Instead, hydrophobic interactions were important for
maintaining the Vif-CBFbeta complex, since it could be disrupted by nonionic
detergent. Site-directed mutagenesis of conserved hydrophobic amino acids
revealed novel residues in Vif that were important for CBFbeta binding and
APOBEC3 inactivation. At least part of the well-characterized HCCH domain
(residues 108 to 139) was required to form a stable Vif-CBFbeta complex. Thus,
the HCCH motif may have a dual role in binding both Cul5 and CBFbeta. Considering
the importance of Vif in HIV-1 infection, this unique Vif-CBFbeta interaction
represents an attractive pharmacological intervention target against HIV-1.
IMPORTANCE: Vif-induced APOBEC3 protein degradation was the first host antiviral
mechanism against HIV-1/simian immunodeficiency virus to be revealed, yet details
regarding which proteins are degraded are not fully demonstrated. Recently, host
cellular factor CBFbeta was found to be essential for Vif to function and promote
viral infectivity. In this study, we present more critical information on the Vif
CBFbeta interaction by revealing that hydrophobicity contributes the most to the
Vif-CBFbeta interaction and locating several novel hydrophobic sites (tryptophans
and phenylalanines) that are conserved among Vif proteins from different
lentiviruses and essential for Vif binding to CBFbeta. Mutations on these sites
result in a reduced/abolished Vif-CBFbeta interaction, leading to the attenuated
potency of Vif on both inducing the degradation of antiviral factors like
APOBEC3G and promoting HIV-1 infectivity. Therefore, information from this study
will help people to further understand how Vif acts against host antiviral
mechanism, which is important for novel anti-HIV-1 drug development.
PMID- 24352441
TI - Epigenetic regulation of HIV-1 latency in astrocytes.
AB - HIV infiltrates the brain at early times postinfection and remains latent within
astrocytes and macrophages. Because astrocytes are the most abundant cell type in
the brain, we evaluated epigenetic regulation of HIV latency in astrocytes. We
have shown that class I histone deacetylases (HDACs) and a lysine-specific
histone methyltransferase, SU(VAR)3-9, play a significant role in silencing of
HIV transcription in astrocytes. Our studies add to a growing body of evidence
demonstrating that astrocytes are a reservoir for HIV.
PMID- 24352442
TI - Quantitative characterization of defective virus emergence by deep sequencing.
AB - Populations of RNA viruses can spontaneously produce variants that differ in
genome size, sequence, and biological activity. Defective variants that lack
essential genes can nevertheless reproduce by coinfecting cells with viable
virus, a process that interferes with virus growth. How such defective
interfering particles (DIPs) change in abundance and biological activity within a
virus population is not known. Here, a prototype RNA virus, vesicular stomatitis
virus (VSV), was cultured for three passages on BHK host cells, and passages were
subjected to Illumina sequencing. Reads from the initial population, when aligned
to the full-length viral sequence (11,161 nucleotides [nt]), distributed
uniformly across the genome. However, during passages two plateaus in read counts
appeared toward the 5' end of the negative-sense viral genome. Analysis by
normalization and a simple sliding-window approach revealed plateau boundaries
that suggested the emergence and enrichment of at least two truncated species
having medium (~5,900 nt) and short (~4,000 nt) genomes. Relative measures of
full-length and truncated species based on read counts were validated by
quantitative reverse transcription-PCR (qRT-PCR). Limit-of-detection analysis
suggests that deep sequencing can be more sensitive than complementary measures
for detecting and quantifying defective particles in a population. Further,
particle counts from transmission electron microscopy, coupled with infectivity
assays, linked the rise in smaller genomes with an increase in truncated
particles and interference activity. In summary, variation in deep sequencing
coverage simultaneously shows the size, location, and relative level of truncated
genome variants, revealing a level of population heterogeneity that is masked by
other measures of viral genomes and particles. IMPORTANCE: We show how deep
sequencing can be used to characterize the emergence, diversity, and relative
abundance of truncated virus variants in virus populations. Adaptation of this
approach to natural isolates may elucidate factors that influence the stability
and persistence of virus populations in nature.
PMID- 24352443
TI - Global panel of HIV-1 Env reference strains for standardized assessments of
vaccine-elicited neutralizing antibodies.
AB - Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody
responses are complicated by the genetic and antigenic variability of the viral
envelope glycoproteins (Envs). To address these issues, suitable reference
strains are needed that are representative of the global epidemic. Several panels
have been recommended previously, but no clear answers have been available on how
many and which strains are best suited for this purpose. We used a statistical
model selection method to identify a global panel of reference Env clones from
among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV
1-infected individuals. The Envs and sera were sampled globally from diverse
geographic locations and represented all major genetic subtypes and circulating
recombinant forms of the virus. Assays with a panel size of only nine viruses
adequately represented the spectrum of HIV-1 serum neutralizing activity seen
with the larger panel of 219 viruses. An optimal panel of nine viruses was
selected and augmented with three additional viruses for greater genetic and
antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with
the final 12-virus panel closely approximated the activity seen with subtype
matched viruses. Moreover, the final panel was highly sensitive for detection of
many of the known broadly neutralizing antibodies. For broader assay
applications, all 12 Env clones were converted to infectious molecular clones
using a proviral backbone carrying a Renilla luciferase reporter gene
(Env.IMC.LucR viruses). This global panel should facilitate highly standardized
assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1
vaccine platforms in different parts of the world. IMPORTANCE: An effective HIV-1
vaccine will need to overcome the extraordinary genetic variability of the virus,
where most variation occurs in the viral envelope glycoproteins that are the sole
targets for neutralizing antibodies. Efforts to elicit broadly cross-reactive
neutralizing antibodies that will protect against infection by most circulating
strains of the virus are guided in part by in vitro assays that determine the
ability of vaccine-elicited antibodies to neutralize genetically diverse HIV-1
variants. Until now, little information was available on how many and which
strains of the virus are best suited for this purpose. We applied robust
statistical methods to evaluate a large neutralization data set and identified a
small panel of viruses that are a good representation of the global epidemic. The
neutralization properties of this new panel of reference strains should
facilitate the development of an effective HIV-1 vaccine.
PMID- 24352444
TI - Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by
antibody-dependent cell-mediated cytotoxicity.
AB - Anti-HIV-1 envelope glycoprotein (Env) antibodies without broadly neutralizing
activity correlated with protection in the RV144 clinical trial, stimulating
interest in other protective mechanisms involving antibodies, such as antibody
dependent cell-mediated cytotoxicity (ADCC). Env epitopes targeted by many
antibodies effective at mediating ADCC are poorly exposed on the unliganded Env
trimer. Here we investigated the mechanism of exposure of ADCC epitopes on Env
and showed that binding of Env and CD4 within the same HIV-1-infected cell
effectively exposes these epitopes. Env capacity to transit to the CD4-bound
conformation is required for ADCC epitope exposure. Importantly, cell surface CD4
downregulation by Nef and Vpu accessory proteins and Vpu-mediated BST-2
antagonism modulate exposure of ADCC-mediating epitopes and reduce the
susceptibility of infected cells to this effector function in vitro.
Significantly, Env conformational changes induced by cell surface CD4 are
conserved among Env from HIV-1 and HIV-2/SIVmac lineages. Altogether, our
observations describe a highly conserved mechanism required to expose ADCC
epitopes that might help explain the evolutionary advantage of downregulation of
cell surface CD4 by the HIV-1 Vpu and Nef proteins. IMPORTANCE: HIV-1 envelope
epitopes targeted by many antibodies effective at mediating antibody-dependent
cell-mediated cytotoxicity (ADCC) are poorly exposed on the unliganded envelope
trimer. Here we investigated the mechanism of exposure of these epitopes and
found that envelope interaction with the HIV-1 CD4 receptor is required to expose
some of these epitopes. Moreover, our results suggest that HIV-1 CD4
downregulation might help avoid the killing of HIV-1-infected cells by this
immune mechanism.
PMID- 24352445
TI - Nucleic acid chaperone activity associated with the arginine-rich domain of human
hepatitis B virus core protein.
AB - Hepatitis B virus (HBV) DNA replication occurs within the HBV icosahedral core
particles. HBV core protein (HBc) contains an arginine-rich domain (ARD) at its
carboxyl terminus. This ARD domain of HBc 149-183 is known to be important for
viral replication but not known to have a structure. Recently, nucleocapsid
proteins of several viruses have been shown to contain nucleic acid chaperone
activity, which can facilitate structural rearrangement of viral genome. Major
features of nucleic acid chaperones include highly basic amino acid residues and
flexible protein structure. To test the nucleic acid chaperone hypothesis for HBc
ARD, we first used the disassembled full-length HBc from Escherichia coli to
analyze the nucleic acid annealing and strand displacement activities. To exclude
the potential contamination of chaperones from E. coli, we designed synthetic HBc
ARD peptides with different lengths and serine phosphorylations. We demonstrated
that HBc ARD peptide can behave like a bona fide nucleic acid chaperone and that
the chaperone activity depends on basic residues of the ARD domain. The loss of
chaperone activity by arginine-to-alanine substitutions in the ARD can be rescued
by restoring basic residues in the ARD. Furthermore, the chaperone activity is
subject to regulation by phosphorylation and dephosphorylation at the HBc ARD.
Interestingly, the HBc ARD can enhance in vitro cleavage activity of RNA
substrate by a hammerhead ribozyme. We discuss here the potential significance of
the HBc ARD chaperone activity in the context of viral DNA replication, in
particular, at the steps of primer translocations and circularization of linear
replicative intermediates. IMPORTANCE: Hepatitis B virus is a major human
pathogen. At present, no effective treatment can completely eradicate the virus
from patients with chronic hepatitis B. We report here a novel chaperone activity
associated with the viral core protein. Our discovery could lead to a new drug
design for more effective treatment against hepatitis B virus in the future.
PMID- 24352446
TI - Hepatitis C virus impairs natural killer cell-mediated augmentation of complement
synthesis.
AB - Natural killer (NK) cells and the complement system play critical roles in the
first line of defense against pathogens. The synthesis of complement components
C4 and C3 is transcriptionally downregulated by hepatitis C virus (HCV) core and
NS5A proteins, and this negative regulation is apparent in chronically HCV
infected patients. In this study, we have examined the potential contribution of
an NK cell line as a model in regulating complement synthesis. Coculture of NK
cells (NK3.3) with human hepatoma cells (Huh7.5) expressing HCV core or NS5A
protein led to a significant increase in C4 and C3 complement synthesis via
enhanced specific transcription factors. Reestablishment of complement protein
expression was found to be mediated by direct interaction between NKG2D on NK
cells and the hepatocyte protein major histocompatibility complex class I-related
chains A and B (MICA/B) and not to be associated with specific cytokine signaling
events. On the other hand, C4 and C3 synthesis remained impaired in a coculture
of NK cells and Huh7.5 cells infected with cell culture-grown HCV. The
association between these two cell types through NKG2D and MICA/B was examined
further, with MICA/B expression in HCV-infected hepatocytes found to remain
inhibited during coculture. Further experiments revealed that the HCV NS2 and
NS5B proteins are responsible for the HCV-associated decrease in MICA/B. These
results suggest that HCV disables a key receptor ligand in infected hepatoma
cells, thereby inhibiting the ability of infected cells to respond to stimuli
from NK cells to positively regulate complement synthesis. IMPORTANCE: The
complement system contributes to the protection of the host from virus infection.
However, the involvement of complement in viral hepatitis has not been well
documented. Whether NK cells affect complement component expression in HCV
infected hepatocytes remains unknown. Here, we have shown how HCV subverts the
ability of NK cells to positively mediate complement protein expression.
PMID- 24352447
TI - Involvement of viral microRNA in the regulation of antiviral apoptosis in shrimp.
AB - Viruses, in particular DNA viruses, generate microRNAs (miRNAs) to control the
expression of host and viral genes. Due to their essential roles in virus-host
interactions, viral miRNAs have attracted extensive investigations in recent
years. To date, however, most studies on viral miRNAs have been conducted in cell
lines. In this study, the viral miRNAs from white spot syndrome virus (WSSV) were
characterized in shrimp in vivo. On the basis of our previous study and small RNA
sequencing in this study, a total of 89 putative WSSV miRNAs were identified. As
revealed by miRNA microarray analysis and Northern blotting, the expression of
viral miRNAs was tissue specific in vivo. The results indicated that the viral
miRNA WSSV-miR-N24 could target the shrimp caspase 8 gene, and this miRNA further
repressed the apoptosis of shrimp hemocytes in vivo. As a result, the number of
WSSV copies in shrimp in vivo was significantly increased compared with the
control level (WSSV only). Therefore, our study presents the first report on the
in vivo molecular events of viral miRNA in antiviral apoptosis.
PMID- 24352448
TI - An ITAM in a nonenveloped virus regulates activation of NF-kappaB, induction of
beta interferon, and viral spread.
AB - Immunoreceptor tyrosine-based activation motifs (ITAMs) are signaling domains
located within the cytoplasmic tails of many transmembrane receptors and
associated adaptor proteins that mediate immune cell activation. ITAMs also have
been identified in the cytoplasmic tails of some enveloped virus glycoproteins.
Here, we identified ITAM sequences in three mammalian reovirus proteins: MU2,
sigma2, and lambda2. We demonstrate for the first time that MU2 is
phosphorylated, contains a functional ITAM, and activates NF-kappaB.
Specifically, MU2 and MUNS recruit the ITAM-signaling intermediate Syk to
cytoplasmic viral factories and this recruitment requires the MU2 ITAM. Moreover,
both the MU2 ITAM and Syk are required for maximal MU2 activation of NF-kappaB. A
mutant virus lacking the MU2 ITAM activates NF-kappaB less efficiently and
induces lower levels of the downstream antiviral cytokine beta interferon (IFN
beta) than does wild-type virus despite similar replication. Notably, the
consequences of these MU2 ITAM effects are cell type specific. In fibroblasts
where NF-kappaB is required for reovirus-induced apoptosis, the MU2 ITAM is
advantageous for viral spread and enhances viral fitness. Conversely, in cardiac
myocytes where the IFN response is critical for antiviral protection and NF
kappaB is not required for apoptosis, the MU2 ITAM stimulates cellular defense
mechanisms and diminishes viral fitness. Together, these results suggest that the
cell type-specific effect of the MU2 ITAM on viral spread reflects the cell type
specific effects of NF-kappaB and IFN-beta. This first demonstration of a
functional ITAM in a nonenveloped virus presents a new mechanism for viral ITAM
mediated signaling with likely organ-specific consequences in the host.
PMID- 24352449
TI - Arabidopsis double-stranded RNA binding protein DRB3 participates in methylation
mediated defense against geminiviruses.
AB - Arabidopsis encodes five double-stranded RNA binding (DRB) proteins. DRB1 and
DRB2 are involved in microRNA (miRNA) biogenesis, while DRB4 functions in
cytoplasmic posttranscriptional small interfering RNA (siRNA) pathways. DRB3 and
DRB5 are not involved in double-stranded RNA (dsRNA) processing but assist in
silencing transcripts targeted by DRB2-associated miRNAs. The goal of this study
was to determine which, if any, of the DRB proteins might also participate in a
nuclear siRNA pathway that leads to geminivirus genome methylation. Here, we
demonstrate that DRB3 functions with Dicer-like 3 (DCL3) and Argonaute 4 (AGO4)
in methylation-mediated antiviral defense. Plants employ repressive viral genome
methylation as an epigenetic defense against geminiviruses, using an RNA-directed
DNA methylation (RdDM) pathway similar to that used to suppress endogenous
invasive DNAs such as transposons. Chromatin methylation inhibits virus
replication and transcription, and methylation-deficient host plants are
hypersusceptible to geminivirus infection. Using a panel of drb mutants, we found
that drb3 plants uniquely exhibit a similar hypersensitivity and that viral
genome methylation is substantially reduced in drb3 compared to wild-type plants.
In addition, like dcl3 and ago4 mutants, drb3 plants fail to recover from
infection and cannot accomplish the viral genome hypermethylation that is
invariably observed in asymptomatic, recovered tissues. Small RNA analysis,
bimolecular fluorescence complementation, and coimmunoprecipitation experiments
show that DRB3 acts downstream of siRNA biogenesis and suggest that it associates
with DCL3 and AGO4 in distinct subnuclear compartments. These studies reveal that
in addition to its previously established role in the miRNA pathway, DRB3 also
functions in antiviral RdDM. IMPORTANCE: Plants use RNA-directed DNA methylation
(RdDM) as an epigenetic defense against geminiviruses. RNA silencing pathways in
Arabidopsis include five double-stranded RNA binding proteins (DRBs) related to
Drosophila R2D2 and mammalian TRBP and PACT. While DRB proteins have defined
roles in miRNA and cytoplasmic siRNA pathways, a role in nuclear RdDM was
elusive. Here, we used the geminivirus system to show that DRB3 is involved in
methylation-mediated antiviral defense. Beginning with a panel of Arabidopsis drb
mutants, we demonstrated that drb3 plants uniquely show enhanced susceptibility
to geminiviruses. Further, like dcl3 and ago4 mutants, drb3 plants fail to
hypermethylate the viral genome, a requirement for host recovery. We also show
that DRB3 physically interacts with the RdDM pathway components DCL3 and AGO4 in
the nucleus. This work highlights the utility of geminiviruses as models for de
novo RdDM and places DRB3 protein in this fundamental epigenetic pathway.
PMID- 24352450
TI - Immunogenicity of novel mumps vaccine candidates generated by genetic
modification.
AB - Mumps is a highly contagious human disease, characterized by lateral or bilateral
nonsuppurative swelling of the parotid glands and neurological complications that
can result in aseptic meningitis or encephalitis. A mumps vaccination program
implemented since the 1960s reduced mumps incidence by more than 99% and kept the
mumps case numbers as low as hundreds of cases per year in the United States
before 2006. However, a large mumps outbreak occurred in vaccinated populations
in 2006 and again in 2009 in the United States, raising concerns about the
efficacy of the vaccination program. Previously, we have shown that clinical
isolate-based recombinant mumps viruses lacking expression of either the V
protein (rMuVDeltaV) or the SH protein (rMuVDeltaSH) are attenuated in a
neurovirulence test using newborn rat brains (P. Xu et al., Virology 417:126-136,
2011, http://dx.doi.org/10.1016/j.virol.2011.05.003; P. Xu et al., J. Virol.
86:1768-1776, 2012, http://dx.doi.org/10.1128/JVI.06019-11) and may be good
candidates for vaccine development. In this study, we examined immunity induced
by rMuVDeltaSH and rMuVDeltaV in mice. Furthermore, we generated recombinant
mumps viruses lacking expression of both the V protein and the SH protein
(rMuVDeltaSHDeltaV). Analysis of rMuVDeltaSHDeltaV indicated that it was stable
in tissue culture cell lines. Importantly, rMuVDeltaSHDeltaV was immunogenic in
mice, indicating that it is a promising candidate for mumps vaccine development.
PMID- 24352451
TI - Role of the goat K222-PrP(C) polymorphic variant in prion infection resistance.
AB - The prion protein-encoding gene (prnp) strongly influences the susceptibility of
small ruminants to transmissible spongiform encephalopathies (TSEs). Hence,
selective breeding programs have been implemented to increase sheep resistance to
scrapie. For goats, epidemiological and experimental studies have provided some
association between certain polymorphisms of the cellular prion protein (PrP(C))
and resistance to TSEs. Among them, the Q/K polymorphism at PrP(C) codon 222
(Q/K222) yielded the most promising results. In this work, we investigated the
individual effects of the K222-PrP(C) variant on the resistance/susceptibility of
goats to TSEs. For that purpose, we generated two transgenic mouse lines,
expressing either the Q222 (wild type) or K222 variant of goat PrP(C). Both mouse
lines were challenged intracerebrally with a panel of TSE isolates. Transgenic
mice expressing the wild-type (Q222) allele were fully susceptible to infection
with all tested isolates, whereas transgenic mice expressing similar levels of
the K222 allele were resistant to all goat scrapie and cattle BSE isolates but
not to goat BSE isolates. Finally, heterozygous K/Q222 mice displayed a reduced
susceptibility to the tested panel of scrapie isolates. These results demonstrate
a highly protective effect of the K222 variant against a broad panel of different
prion isolates and further reinforce the argument supporting the use of this
variant in breeding programs to control TSEs in goat herds. IMPORTANCE: The
objective of this study was to determine the role of the K222 variant of the
prion protein (PrP) in the susceptibility/resistance of goats to transmissible
spongiform encephalopathies (TSEs). Results showed that transgenic mice
expressing the goat K222-PrP polymorphic variant are resistant to scrapie and
bovine spongiform encephalopathy (BSE) agents. This protective effect was also
observed in heterozygous Q/K222 animals. Therefore, the single amino acid
exchange from Q to K at codon 222 of the cellular prion protein provides
resistance against TSEs. All the results presented here support the view that the
K222 polymorphic variant is a good candidate for selective breeding programs to
control and eradicate scrapie in goat herds.
PMID- 24352452
TI - Papillomavirus E6 PDZ interactions can be replaced by repression of p53 to
promote episomal human papillomavirus genome maintenance.
AB - Cancer-associated human papillomaviruses (HPVs) express E6 oncoproteins that
target the degradation of p53 and have a carboxy-terminal PDZ ligand that is
required for stable episomal maintenance of the HPV genome. We find that the E6
PDZ ligand can be deleted and the HPV genome stably maintained if cellular p53 is
inactivated. This indicates that the E6-PDZ interaction promotes HPV genome
maintenance at least in part by neutralization of an activity that can arise from
residual undegraded p53.
PMID- 24352453
TI - Differential impact of PD-1 and/or interleukin-10 blockade on HIV-1-specific CD4
T cell and antigen-presenting cell functions.
AB - Antigen persistence in chronic infections and cancer upregulates inhibitory
networks, such as the PD-1 and interleukin-10 (IL-10) pathways, that impair
immunity and lead to disease progression. These pathways are attractive targets
for immunotherapy, as demonstrated by recent clinical trials of PD-1/PD-L1
blockade in cancer patients. However, in HIV-1 infection not all subjects respond
to inhibition of either pathway and the mechanistic interactions between these
two networks remain to be better defined. Here we demonstrate that in vitro
blockade of PD-L1 and/or IL-10Ralpha results in markedly different profiles of
HIV-1-specific CD4 T cell restoration. Whereas PD-L1 blockade leads to balanced
increase in gamma interferon (IFN-gamma), IL-2, and IL-13 secretion, IL-10Ralpha
blockade preferentially restores IFN-gamma production. In viremic subjects,
combined PD-L1/IL-10Ralpha blockade results in a striking 10-fold increase in IFN
gamma secretion by HIV-1-specific CD4 T cells that is not observed in subjects
with spontaneous (elite controllers) or therapy-induced control of viral
replication. In contrast to the dramatic increase in IFN-gamma production,
concurrent blockade has a marginal additive effect on IL-2 production, IL-13
secretion, and HIV-1-specific CD4 T cell proliferation. IFN-gamma produced by
Thelper cells upregulates PD-L1, HLA I/II, and IL-12 expression by monocytes. The
effect of combined blockade on IFN-gamma was dependent on reciprocal
reinforcement through IL-12. These studies provide crucial information on the
different immunoregulatory qualities of PD-1 and IL-10 in progressive disease and
link exhausted virus-specific CD4 T cells and monocytes in the regulation of IFN
gamma and IL-12 secretion. IMPORTANCE: Infection with HIV results in most people
in uncontrolled viral replication and progressive weakening of the body defenses.
In the absence of antiviral therapy, this process results in clinical disease, or
AIDS. An important reason why HIV continues to multiply is that a population of
white blood cells called CD4 T cells that targets the virus fails to work
properly. At least part of this impairment is under the control of inhibitory
mechanisms that can be blocked to improve the function of these CD4 T cells. In
this report, we show that blocking one or two of the molecules involved, called
PD-1 and IL-10, has different effects on the individual functions of these cells
and that one is strongly improved. We investigate how these effects are caused by
interactions between CD4 T cells and antigen-presenting cells. These observations
can have implications for new therapeutic approaches in HIV infection.
PMID- 24352454
TI - Adenovirus E1B 19-kilodalton protein modulates innate immunity through apoptotic
mimicry.
AB - Cells that undergo apoptosis in response to chemical or physical stimuli repress
inflammatory reactions, but cells that undergo nonapoptotic death in response to
such stimuli lack this activity. Whether cells dying from viral infection exhibit
a cell death-type modulatory effect on inflammatory reactions is unknown. We
compared the effects on macrophage inflammatory responses of cells dying an
apoptotic or a nonapoptotic death as a result of adenoviral infection. The
results were exactly opposite to the predictions from the conventional paradigm.
Cells dying by apoptosis induced by infection with an adenovirus type 5 (Ad5) E1B
19-kilodalton (E1B 19K) gene deletion mutant did not repress macrophage NF-kappaB
activation or cytokine responses to proinflammatory stimuli, whereas cells dying
a nonapoptotic death from infection with E1B 19K-competent, wild-type Ad5
repressed these macrophage inflammatory responses as well as cells undergoing
classical apoptosis in response to chemical injury. The immunorepressive, E1B 19K
related cell death activity depended upon direct contact of the virally infected
corpses with responder macrophages. Replacement of the viral E1B 19K gene with
the mammalian Bcl-2 gene in cis restored the nonapoptotic, immunorepressive cell
death activity of virally infected cells. These results define a novel function
of the antiapoptotic, adenoviral E1B 19K protein that may limit local host innate
immune inflammation during accumulation of virally infected cells at sites of
infection and suggest that E1B 19K-deleted, replicating adenoviral vectors might
induce greater inflammatory responses to virally infected cells than E1B 19K
positive vectors, because of the net effect of their loss-of-function mutation.
IMPORTANCE: We observed that cells dying a nonapoptotic cell death induced by
adenovirus infection repressed macrophage proinflammatory responses while cells
dying by apoptosis induced by infection with an E1B 19K deletion mutant virus did
not repress macrophage proinflammatory responses and enhanced some cytokine
responses. Our results define a new function of the antiapoptotic, adenoviral
protein E1B 19K, which we have termed "apoptotic mimicry." Our studies suggest
the possibility that the presence or absence of this E1B 19K function could alter
the immunological outcome of both natural and therapeutic adenoviral infections.
For example, emerging, highly immunopathogenic adenovirus serotypes might induce
increased host inflammatory responses as a result of altered E1B 19K function or
expression. It is also possible that engineered variations in E1B 19K
expression/function could be created during adenovirus vector design that would
increase the therapeutic efficacy of replicating adenovirus vectors for vaccines
or oncolytic viral targeting of neoplastic cells.
PMID- 24352455
TI - Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B
cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D.
AB - Broadly neutralizing antibodies (bNAbs) against HIV-1 are generated during HIV-1
infection but have not yet been elicited by immunization with recombinant forms
of the viral envelope glycoprotein (Env; the target of anti-HIV-1 neutralizing
antibodies). A particular type of bNAb targets the CD4-binding site (CD4-BS)
region of Env. These antibodies are derived from a limited number of VH/VL genes
and can bind to and neutralize diverse HIV-1 strains. Recent reports have
demonstrated the limited potential of Env to activate B cells expressing the
germline B cell receptor (BCR) forms of anti-CD4-BS bNAbs. A potential reason for
the lack of elicitation of anti-CD4-BS bNAbs by Env immunogens is the absence of
stimulation of naive B cells expressing the germline BCRs of such antibodies.
Several bNAbs have been isolated from HIV-1-infected subjects that target other
structurally conserved regions of Env. How frequently Env immunogens stimulate
the germline BCRs that give rise to bNAbs that target Env regions other than the
CD4-BS is not well understood. Here, we investigated the interactions between
diverse Envs and the BCRs of known bNAbs targeting not only the CD4-BS but also
conserved elements of the second and third variable Env regions. Our results
indicate that Env is generally ineffective in engaging germline BCRs of bNAbs
irrespective of their epitope target. Potentially, this is the result of viral
evolutionary mechanisms adopted to escape broadly neutralizing antibody
responses. Our results also suggest that a single Env capable of activating
germline BCRs that target distinct Env epitopes will be very difficult to
identify or to design. IMPORTANCE: Broadly neutralizing antibodies against HIV-1
are thought to be an important component of the immune responses that a
successful vaccine should elicit. Broadly neutralizing antibodies are generated
by a subset of those infected by HIV-1, but so far, they have not been generated
by immunization with recombinant Envelope (Env, the target of anti-HIV-1
neutralizing antibodies). Here, we provide evidence that the inability of Env to
elicit the production of broadly neutralizing antibodies is due to the inability
of diverse Envs to engage the germline B cell receptor forms of known broadly
neutralizing antibodies.
PMID- 24352456
TI - Recruitment of PI4KIIIbeta to coxsackievirus B3 replication organelles is
independent of ACBD3, GBF1, and Arf1.
AB - Members of the Enterovirus (poliovirus [PV], coxsackieviruses, and human
rhinoviruses) and Kobuvirus (Aichi virus) genera in the Picornaviridae family
rely on PI4KIIIbeta (phosphatidylinositol-4-kinase IIIbeta) for efficient
replication. The small membrane-anchored enteroviral protein 3A recruits
PI4KIIIbeta to replication organelles, yet the underlying mechanism has remained
elusive. Recently, it was shown that kobuviruses recruit PI4KIIIbeta through
interaction with ACBD3 (acyl coenzyme A [acyl-CoA]-binding protein domain 3), a
novel interaction partner of PI4KIIIbeta. Therefore, we investigated a possible
role for ACBD3 in recruiting PI4KIIIbeta to enterovirus replication organelles.
Although ACBD3 interacted directly with coxsackievirus B3 (CVB3) 3A, its
depletion from cells by RNA interference did not affect PI4KIIIbeta recruitment
to replication organelles and did not impair CVB3 RNA replication. Enterovirus 3A
was previously also proposed to recruit PI4KIIIbeta via GBF1/Arf1, based on the
known interaction of 3A with GBF1, an important regulator of secretory pathway
transport and a guanine nucleotide exchange factor (GEF) of Arf1. However, our
results demonstrate that inhibition of GBF1 or Arf1 either by pharmacological
inhibition or depletion with small interfering RNA (siRNA) treatment did not
affect the ability of 3A to recruit PI4KIIIbeta. Furthermore, we show that a 3A
mutant that no longer binds GBF1 was capable of recruiting PI4KIIIbeta, even in
ACBD3-depleted cells. Together, our findings indicate that unlike originally
envisaged, coxsackievirus recruits PI4KIIIbeta to replication organelles
independently of ACBD3 and GBF1/Arf1. IMPORTANCE: A hallmark of enteroviral
infection is the generation of new membranous structures to support viral RNA
replication. The functionality of these "replication organelles" depends on the
concerted actions of both viral nonstructural proteins and co-opted host factors.
It is thus essential to understand how these structures are formed and which
cellular components are key players in this process. GBF1/Arf1 and ACBD3 have
been proposed to contribute to the recruitment of the essential lipid-modifying
enzyme PI4KIIIbeta to enterovirus replication organelles. Here we show that the
enterovirus CVB3 recruits PI4KIIIbeta by a mechanism independent of both
GBF1/Arf1 and ACBD3. This study shows that the strategy employed by
coxsackievirus to recruit PI4KIIIbeta to replication organelles is far more
complex than initially anticipated.
PMID- 24352457
TI - Mechanism of neutralization of herpes simplex virus by antibodies directed at the
fusion domain of glycoprotein B.
AB - Glycoprotein B (gB), the fusogen of herpes simplex virus (HSV), is a class III
fusion protein with a trimeric ectodomain of known structure for the postfusion
state. Seen by negative-staining electron microscopy, it presents as a rod with
three lobes (base, middle, and crown). gB has four functional regions (FR),
defined by the physical location of epitopes recognized by anti-gB neutralizing
monoclonal antibodies (MAbs). Located in the base, FR1 contains two internal
fusion loops (FLs) and is the site of gB-lipid interaction (the fusion domain).
Many of the MAbs to FR1 are neutralizing, block cell-cell fusion, and prevent the
association of gB with lipid, suggesting that these MAbs affect FL function. Here
we characterize FR1 epitopes by using electron microscopy to visualize purified
Fab-gB ectodomain complexes, thus confirming the locations of several epitopes
and localizing those of MAbs DL16 and SS63. We also generated MAb-resistant
viruses in order to localize the SS55 epitope precisely. Because none of the
epitopes of our anti-FR1 MAbs mapped to the FLs, we hyperimmunized rabbits with
FL1 or FL2 peptides to generate polyclonal antibodies (PAbs). While the anti-FL1
PAb failed to bind gB, the anti-FL2 PAb had neutralizing activity, implying that
the FLs become exposed during virus entry. Unexpectedly, the anti-FL2 PAb (and
the anti-FR1 MAbs) bound to liposome-associated gB, suggesting that their
epitopes are accessible even when the FLs engage lipid. These studies provide
possible mechanisms of action for HSV neutralization and insight into how gB FR1
contributes to viral fusion. IMPORTANCE: For herpesviruses, such as HSV, entry
into a target cell involves transfer of the capsid-encased genome of the virus to
the target cell after fusion of the lipid envelope of the virus with a lipid
membrane of the host. Virus-encoded glycoproteins in the envelope are responsible
for fusion. Antibodies to these glycoproteins are important biological tools,
providing a way of examining how fusion works. Here we used electron microscopy
and other techniques to study a panel of anti-gB antibodies. Some, with virus
neutralizing activity, impair gB-lipid association. We also generated a peptide
antibody against one of the gB fusion loops; its properties provide insight into
the way the fusion loops function as gB transits from its prefusion form to an
active fusogen.
PMID- 24352458
TI - Interaction of foot-and-mouth disease virus nonstructural protein 3A with host
protein DCTN3 is important for viral virulence in cattle.
AB - Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially
conserved protein of 153 amino acids in most FMDVs examined to date. The role of
3A in virus growth and virulence within the natural host is not well understood.
Using a yeast two-hybrid approach, we identified cellular protein DCTN3 as a
specific host binding partner for 3A. DCTN3 is a subunit of the dynactin complex,
a cofactor for dynein, a motor protein. The dynactin-dynein duplex has been
implicated in several subcellular functions involving intracellular organelle
transport. The 3A-DCTN3 interaction identified by the yeast two-hybrid approach
was further confirmed in mammalian cells. Overexpression of DCTN3 or proteins
known to disrupt dynein, p150/Glued and 50/dynamitin, resulted in decreased FMDV
replication in infected cells. We mapped the critical amino acid residues in the
3A protein that mediate the protein interaction with DCTN3 by mutational analysis
and, based on that information, we developed a mutant harboring the same
mutations in O1 Campos FMDV (O1C3A-PLDGv). Although O1C3A-PLDGv FMDV and its
parental virus (O1Cv) grew equally well in LFBK-alphavbeta6, O1C3A-PLDGv virus
exhibited a decreased ability to replicate in primary bovine cell cultures.
Importantly, O1C3A-PLDGv virus exhibited a delayed disease in cattle compared to
the virulent parental O1Campus (O1Cv). Virus isolated from lesions of animals
inoculated with O1C3A-PLDGv virus contained amino acid substitutions in the area
of 3A mediating binding to DCTN3. Importantly, 3A protein harboring similar amino
acid substitutions regained interaction with DCTN3, supporting the hypothesis
that DCTN3 interaction likely contributes to virulence in cattle. IMPORTANCE: The
objective of this study was to understand the possible role of a FMD virus
protein 3A, in causing disease in cattle. We have found that the cellular
protein, DCTN3, is a specific binding partner for 3A. It was shown that
manipulation of DCTN3 has a profound effect in virus replication. We developed a
FMDV mutant virus that could not bind DCTN3. This mutant virus exhibited a
delayed disease in cattle compared to the parental strain highlighting the role
of the 3A-DCTN3 interaction in virulence in cattle. Interestingly, virus isolated
from lesions of animals inoculated with mutant virus contained mutations in the
area of 3A that allowed binding to DCTN3. This highlights the importance of the
3A-DCTN3 interaction in FMD virus virulence and provides possible mechanisms of
virus attenuation for the development of improved FMD vaccines.
PMID- 24352459
TI - Analysis of T cell responses during active varicella-zoster virus reactivation in
human ganglia.
AB - Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and
herpes zoster (shingles). During varicella, the virus establishes latency within
the sensory ganglia and can reactivate to cause herpes zoster, but the immune
responses that occur in ganglia during herpes zoster have not previously been
defined. We examined ganglia obtained from individuals who, at the time of death,
had active herpes zoster. Ganglia innervating the site of the cutaneous herpes
zoster rash showed evidence of necrosis, secondary to vasculitis, or localized
hemorrhage. Despite this, there was limited evidence of VZV antigen expression,
although a large inflammatory infiltrate was observed. Characterization of the
infiltrating T cells showed a large number of infiltrating CD4(+) T cells and
cytolytic CD8(+) T cells. Many of the infiltrating T cells were closely
associated with neurons within the reactivated ganglia, yet there was little
evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the
expression of major histocompatibility complex class I (MHC-I) and MHC-II
molecules was observed on satellite glial cells, implying these cells play an
active role in directing the immune response during herpes zoster. This is the
first detailed characterization of the interaction between T cells and neuronal
cells within ganglia obtained from patients suffering herpes zoster at the time
of death and provides evidence that CD4(+) and cytolytic CD8(+) T cell responses
play an important role in controlling VZV replication in ganglia during active
herpes zoster. IMPORTANCE: VZV is responsible for both varicella (chickenpox) and
herpes zoster (shingles). During varicella, the virus establishes a life-long
dormant infection within the sensory ganglia and can reawaken to cause herpes
zoster, but the immune responses that occur in ganglia during herpes zoster have
not previously been defined. We examined ganglia obtained from individuals who,
at the time of death, had active herpes zoster. We found that specific T cell
subsets are likely to play an important role in controlling VZV replication in
ganglia during active herpes zoster.
PMID- 24352460
TI - An increase in acid resistance of foot-and-mouth disease virus capsid is mediated
by a tyrosine replacement of the VP2 histidine previously associated with VP0
cleavage.
AB - The foot-and-mouth disease virus (FMDV) capsid is highly acid labile, but
introduction of amino acid replacements, including an N17D change in VP1, can
increase its acid resistance. Using mutant VP1 N17D as a starting point, we
isolated a virus with higher acid resistance carrying an additional replacement,
VP2 H145Y, in a residue highly conserved among picornaviruses, which has been
proposed to be responsible for VP0 cleavage. This mutant provides an example of
the multifunctionality of picornavirus capsid residues.
PMID- 24352461
TI - Human enterovirus 71 uncoating captured at atomic resolution.
AB - Human enterovirus 71 (EV71) is the major causative agent of severe hand-foot-and
mouth diseases (HFMD) in young children, and structural characterization of EV71
during its life cycle can aid in the development of therapeutics against HFMD.
Here, we present the atomic structures of the full virion and an uncoating
intermediate of a clinical EV71 C4 strain to illustrate the structural changes in
the full virion that lead to the formation of the uncoating intermediate prepared
for RNA release. Although the VP1 N-terminal regions observed to penetrate
through the junction channel at the quasi-3-fold axis in the uncoating
intermediate of coxsackievirus A16 were not observed in the EV71 uncoating
intermediate, drastic conformational changes occur in this region, as has been
observed in all capsid proteins. Additionally, the RNA genome interacts with the
N-terminal extensions of VP1 and residues 32 to 36 of VP3, both of which are
situated at the bottom of the junction. These observations highlight the
importance of the junction for genome release. Furthermore, EV71 uncoating is
associated with apparent rearrangements and expansion around the 2- and 5-fold
axes without obvious changes around the 3-fold axes. Therefore, these structures
enabled the identification of hot spots for capsid rearrangements, which led to
the hypothesis that the protomer interface near the junction and the 2-fold axis
permits the opening of large channels for the exit of polypeptides and viral RNA,
which is an uncoating mechanism that is likely conserved in enteroviruses.
IMPORTANCE: Human enterovirus 71 (EV71) is the major causative agent of severe
hand-foot-and-mouth diseases (HFMD) in young children. EV71 contains an RNA
genome protected by an icosahedral capsid shell. Uncoating is essential in EV71
life cycle, which is characterized by conformational changes in the capsid to
facilitate RNA release into host cell. Here we present the atomic structures of
the full virion and an uncoating intermediate of a clinical C4 strain of EV71.
Structural analysis revealed drastic conformational changes associated with
uncoating in all the capsid proteins near the junction at the quasi-3-fold axis
and protein-RNA interactions at the bottom of the junction in the uncoating
intermediate. Significant capsid rearrangements also occur at the icosahedral 2-
and 5-fold axes but not at the 3-fold axis. Taking the results together, we
hypothesize that the junction and nearby areas are hot spots for capsid breaches
for the exit of polypeptides and viral RNA during uncoating.
PMID- 24352462
TI - Morphogenesis of pestiviruses: new insights from ultrastructural studies of
strain Giraffe-1.
AB - Knowledge on the morphogenesis of pestiviruses is limited due to low virus
production in infected cells. In order to localize virion morphogenesis and
replication sites of pestiviruses and to examine intracellular virion transport,
a cell culture model was established to facilitate ultrastructural studies. Based
on results of virus growth kinetic analysis and quantification of viral RNA,
pestivirus strain Giraffe-1 turned out to be a suitable candidate for studies on
virion generation and export from culture cells. Using conventional transmission
electron microscopy and single-tilt electron tomography, we found virions located
predominately in the lumen of the endoplasmic reticulum (ER) in infected cells
and were able to depict the budding process of virions at ER membranes.
Colocalization of the viral core protein and the envelope glycoprotein E2 with
the ER marker protein disulfide isomerase (PDI) was demonstrated by immunogold
labeling of cryosections. Moreover, pestivirions could be shown in transport
vesicles and the Golgi complex and during exocytosis. Interestingly, viral capsid
protein and double-stranded RNA (dsRNA) were detected in multivesicular bodies
(MVBs), which implies that the endosomal compartment plays a role in pestiviral
replication. Significant cellular membrane alterations such as those described
for members of the Flavivirus and Hepacivirus genera were not found. Based on the
gained morphological data, we present a consistent model of pestivirus
morphogenesis.
PMID- 24352463
TI - Genetic complementation of hepatitis C virus nonstructural protein functions
associated with replication exhibits requirements that differ from those for
virion assembly.
AB - Within the polyprotein encoded by hepatitis C virus (HCV), the minimum components
required for viral RNA replication lie in the NS3-5B region, while virion
assembly requires expression of all virus components. Here, we have employed
complementation systems to examine the role that HCV polyprotein precursors play
in RNA replication and virion assembly. In a trans-complementation assay, an HCV
NS3-5A polyprotein precursor was required to facilitate efficient complementation
of a replication-defective mutation in NS5A. However, this requirement for
precursor expression was partially alleviated when a second functional copy of
NS5A was expressed from an additional upstream cistron within the RNA to be
rescued. In contrast, rescue of a virion assembly mutation in NS5A was more
limited but exhibited little or no requirement for expression of functional NS5A
as a precursor, even when produced in the context of a second replicating helper
RNA. Furthermore, expression of NS5A alone from an additional cistron within a
replicon construct gave greater rescue of virion assembly in cis than in trans.
Combined with the findings of confocal microscope analysis examining the extent
to which the two copies of NS5A from the various expression systems colocalize,
the results point to NS3-5A playing a role in facilitating the integration of
nonstructural (NS) proteins into viral membrane-associated foci, with this
representing an early stage in the steps leading to replication complex
formation. The data further imply that HCV employs a minor virion assembly
pathway that is independent of replication. IMPORTANCE: In hepatitis C virus
infected cells, replication is generally considered an absolute prerequisite for
virus particle formation. Here we investigated the role that the viral protein
NS5A has in both replication and particle assembly using complementation assays
and microscopy. We found that efficient rescue of replication required NS5A to be
expressed as part of a larger polyprotein, and this correlated with detection of
NS5A at sites where replication occurred. In contrast, rescue of particle
assembly did not require expression of NS5A within the context of a polyprotein.
Interestingly, although only partial restoration of particle assembly was
possible by complementation, that proportion that could be rescued benefitted
from expressing NS5A from the same RNA being packaged. Collectively, these
findings provide new insight into aspects of polyprotein function. They also
support the existence of a minor virion assembly pathway that bypasses
replication.
PMID- 24352464
TI - A novel recombinant retrovirus in the genomes of modern birds combines features
of avian and mammalian retroviruses.
AB - Endogenous retroviruses (ERVs) represent ancestral sequences of modern
retroviruses or their extinct relatives. The majority of ERVs cluster alongside
exogenous retroviruses into two main groups based on phylogenetic analyses of the
reverse transcriptase (RT) enzyme. Class I includes gammaretroviruses, and class
II includes lentiviruses and alpha-, beta-, and deltaretroviruses. However,
analyses of the transmembrane subunit (TM) of the envelope glycoprotein (env)
gene result in a different topology for some retroviruses, suggesting
recombination events in which heterologous env sequences have been acquired. We
previously demonstrated that the TM sequences of five of the six genera of
orthoretroviruses can be divided into three types, each of which infects a
distinct set of vertebrate classes. Moreover, these classes do not always overlap
the host range of the associated RT classes. Thus, recombination resulting in
acquisition of a heterologous env gene could in theory facilitate cross-species
transmissions across vertebrate classes, for example, from mammals to reptiles.
Here we characterized a family of class II avian ERVs, "TgERV-F," that acquired a
mammalian gammaretroviral env sequence. Although TgERV-F clusters near a sister
clade to alpharetroviruses, its genome also has some features of
betaretroviruses. We offer evidence that this unusual recombinant has circulated
among several avian orders and may still have infectious members. In addition to
documenting the infection of a nongalliform avian species by a mammalian
retrovirus, TgERV-F also underscores the importance of env sequences in
reconstructing phylogenies and supports a possible role for env swapping in
allowing cross-species transmissions across wide taxonomic distances. IMPORTANCE:
Retroviruses can sometimes acquire an envelope gene (env) from a distantly
related retrovirus. Since env is a key determinant of host range, such an event
affects the host range of the recombinant virus and can lead to the creation of
novel retroviral lineages. Retroviruses insert viral DNA into the host DNA during
infection, and therefore vertebrate genomes contain a "fossil record" of
endogenous retroviral sequences thought to represent past infections of germ
cells. We examined endogenous retroviral sequences in avian genomes for evidence
of recombination events involving env. Although cross-species transmissions of
retroviruses between vertebrate classes (from mammals to birds, for example) are
thought to be rare, we here characterized a group of avian retroviruses that
acquired an env sequence from a mammalian retrovirus. We offer evidence that this
unusual recombinant circulated among songbirds 2 to 4 million years ago and has
remained active into the recent past.
PMID- 24352465
TI - Pathogenic mutations within the hydrophobic domain of the prion protein lead to
the formation of protease-sensitive prion species with increased lethality.
AB - Prion diseases are a group of fatal and incurable neurodegenerative diseases
affecting both humans and animals. The principal mechanism of these diseases
involves the misfolding the host-encoded cellular prion protein, PrP(C), into the
disease-associated isoform, PrP(Sc). Familial forms of human prion disease
include those associated with the mutations G114V and A117V, which lie in the
hydrophobic domain of PrP. Here we have studied the murine homologues (G113V and
A116V) of these mutations using cell-based and animal models of prion infection.
Under normal circumstances, the mutant forms of PrP(C) share similar processing,
cellular localization, and physicochemical properties with wild-type mouse PrP
(MoPrP). However, upon exposure of susceptible cell lines expressing these
mutants to infectious prions, very low levels of protease-resistant aggregated
PrP(Sc) are formed. Subsequent mouse bioassay revealed high levels of infectivity
present in these cells. Thus, these mutations appear to limit the formation of
aggregated PrP(Sc), giving rise to the accumulation of a relatively soluble,
protease sensitive, prion species that is highly neurotoxic. Given that these
mutations lie next to the glycine-rich region of PrP that can abrogate prion
infection, these findings provide further support for small, protease-sensitive
prion species having a significant role in the progression of prion disease and
that the hydrophobic domain is an important determinant of PrP conversion.
IMPORTANCE: Prion diseases are transmissible neurodegenerative diseases
associated with an infectious agent called a prion. Prions are comprised of an
abnormally folded form of the prion protein (PrP) that is normally resistant to
enzymes called proteases. In humans, prion disease can occur in individuals who
inherited mutations in the prion protein gene. Here we have studied the effects
of two of these mutations and show that they influence the properties of the
prions that can be formed. We show that the mutants make highly infectious prions
that are more sensitive to protease treatment. This study highlights a certain
region of the prion protein as being involved in this effect and demonstrates
that prions are not always resistant to protease treatment.
PMID- 24352466
TI - Human T-cell leukemia virus type 1 Tax-deregulated autophagy pathway and c-FLIP
expression contribute to resistance against death receptor-mediated apoptosis.
AB - The human T-cell leukemia virus type 1 (HTLV-1) Tax protein is considered to play
a central role in the process that leads to adult T-cell leukemia/lymphoma (ATL)
and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1
Tax-expressing cells show resistance to apoptosis induced by Fas ligand (FasL)
and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The
regulation of Tax on the autophagy pathway in HeLa cells and peripheral T cells
was recently reported, but the function and underlying molecular mechanism of the
Tax-regulated autophagy are not yet well defined. Here, we report that HTLV-1 Tax
deregulates the autophagy pathway, which plays a protective role during the death
receptor (DR)-mediated apoptosis of human U251 astroglioma cells. The cellular
FLICE-inhibitory protein (c-FLIP), which is upregulated by Tax, also contributes
to the resistance against DR-mediated apoptosis. Both Tax-induced autophagy and
Tax-induced c-FLIP expression require Tax-induced activation of IkappaB kinases
(IKK). Furthermore, Tax-induced c-FLIP expression is regulated through the Tax
IKK-NF-kappaB signaling pathway, whereas Tax-triggered autophagy depends on the
activation of IKK but not the activation of NF-kappaB. In addition, DR-mediated
apoptosis is correlated with the degradation of Tax, which can be facilitated by
the inhibitors of autophagy. IMPORTANCE: Our study reveals that Tax-deregulated
autophagy is a protective mechanism for DR-mediated apoptosis. The molecular
mechanism of Tax-induced autophagy is also illuminated, which is different from
Tax-increased c-FLIP. Tax can be degraded via manipulation of autophagy and TRAIL
induced apoptosis. These results outline a complex regulatory network between and
among apoptosis, autophagy, and Tax and also present evidence that autophagy
represents a new possible target for therapeutic intervention for the HTVL-1
related diseases.
PMID- 24352468
TI - Sequences related to SUMO interaction motifs in herpes simplex virus 1 protein
ICP0 act cooperatively to stimulate virus infection.
AB - Herpes simplex virus type 1 immediate-early protein ICP0 is an E3 ubiquitin
ligase of the RING finger class that degrades several cellular proteins during
infection. This activity is essential for its functions in stimulating efficient
lytic infection and productive reactivation from latency. ICP0 targets a number
of proteins that are modified by the small ubiquitin-like SUMO family of
proteins, and it includes a number of short sequences that are related to SUMO
interaction motifs (SIMs). Therefore, ICP0 has characteristics that are related
to those of cellular SUMO-targeted ubiquitin ligase enzymes. Here, we analyze the
impact of mutation of a number of SIM-like sequences (SLSs) within ICP0 on HSV-1
replication and gene expression and their requirement for ICP0-mediated
degradation of both sumoylated and unmodified promyelocytic leukemia (PML) and
other sumoylated cellular proteins. One SLS in the central portion of the ICP0
sequence (SLS4) was found to be absolutely required for targeting cellular
sumoylated species in general and sumoylated forms of PML other than those of PML
isoform I. Mutation of a group of SLSs in the C-terminal quarter of ICP0 also
reduced ICP0-mediated degradation of sumoylated PML in a cooperative manner.
Although mutation of individual SLSs caused only modest decreases in viral
replication, combined mutation of SLS4 with SLS sequences in the C-terminal
quarter of the protein reduced plaque formation efficiency by up to two orders of
magnitude. These results provide further evidence that the biological activities
of ICP0 are connected with host cell sumoylation events. IMPORTANCE: Herpes
simplex virus type 1 protein ICP0 plays important roles in regulating the initial
stages of lytic infection and productive reactivation from latency. ICP0 mediates
its effects through inducing the degradation of cellular proteins that have
repressive effects on viral gene expression. An increasing number of cellular
proteins are known to be sensitive to ICP0-mediated degradation; therefore, it is
important to understand how ICP0 selects its substrates for degradation. This
study identifies sequence motifs within ICP0 that are involved in targeting
cellular proteins that are modified by the SUMO family of ubiquitin-like proteins
and describes how mutation of combinations of these motifs causes a 100-fold
defect in viral infectivity.
PMID- 24352467
TI - Phosphorylation of a herpes simplex virus 1 dUTPase by a viral protein kinase,
Us3, dictates viral pathogenicity in the central nervous system but not at the
periphery.
AB - Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical for
viral pathogenicity in both mouse peripheral sites (e.g., eyes and vaginas) and
in the central nervous systems (CNS) of mice after intracranial and peripheral
inoculations, respectively. Whereas some Us3 substrates involved in Us3
pathogenicity in peripheral sites have been reported, those involved in Us3
pathogenicity in the CNS remain to be identified. We recently reported that Us3
phosphorylated HSV-1 dUTPase (vdUTPase) at serine 187 (Ser-187) in infected
cells, and this phosphorylation promoted viral replication by regulating optimal
enzymatic activity of vdUTPase. In the present study, we show that the
replacement of vdUTPase Ser-187 by alanine (S187A) significantly reduced viral
replication and virulence in the CNS of mice following intracranial inoculation
and that the phosphomimetic substitution at vdUTPase Ser-187 in part restored the
wild-type viral replication and virulence. Interestingly, the S187A mutation in
vdUTPase had no effect on viral replication and pathogenic effects in the eyes
and vaginas of mice after ocular and vaginal inoculation, respectively.
Similarly, the enzyme-dead mutation in vdUTPase significantly reduced viral
replication and virulence in the CNS of mice after intracranial inoculation,
whereas the mutation had no effect on viral replication and pathogenic effects in
the eyes and vaginas of mice after ocular and vaginal inoculation, respectively.
These observations suggested that vdUTPase was one of the Us3 substrates
responsible for Us3 pathogenicity in the CNS and that the CNS-specific virulence
of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation.
IMPORTANCE: Herpes simplex virus 1 (HSV-1) encodes a viral protein kinase Us3
which is critical for pathogenicity both in peripheral sites and in the central
nervous systems (CNS) of mice following peripheral and intracranial inoculations,
respectively. Whereas some Us3 substrates involved in Us3 pathogenicity in
peripheral sites have been reported, those involved in Us3 pathogenicity in the
CNS remain to be identified. Here, we report that Us3 phosphorylation of viral
dUTPase (vdUTPase) at serine 187 (Ser-187), which has been shown to promote the
vdUTPase activity, appears to be critical for viral virulence in the CNS but not
for pathogenic effects in peripheral sites. Since HSV proteins critical for viral
virulence in the CNS are, in almost all cases, also involved in viral
pathogenicity at peripheral sites, this phosphorylation event is a unique report
of a specific mechanism involved in HSV-1 virulence in the CNS.
PMID- 24352469
TI - Highly pathogenic porcine reproductive and respiratory syndrome virus induces
prostaglandin E2 production through cyclooxygenase 1, which is dependent on the
ERK1/2-p-C/EBP-beta pathway.
AB - Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly
pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is
characterized by high fever and high mortality. However, the mechanism underlying
the fever induction is still unknown. Prostaglandin E2 (PGE2), synthesized by
cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In
this study, we found that PGE2, together with COX-1, was significantly elevated
by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated
kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger
COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct
binding of p-C/EBP-beta to the COX-1 promoter by luciferase reporter and
chromatin immunoprecipitation assays. In addition, silencing of C/EBP-beta
remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV
infection. Taken together, our results indicate that HP-PPRSV elicits the
expression of COX-1 through the ERK1/2-p-C/EBP-beta signaling pathway, resulting
in the increase of PGE2, which might be the cause of high fever in infected pigs.
Our findings might provide new insights into the molecular mechanisms underlying
the pathogenesis of HP-PRRSV infection. IMPORTANCE: The atypical PRRS caused by
HP-PRRSV was characterized by high fever, high morbidity, and high mortality in
pigs of all ages, yet how HP-PRRSV induces high fever in pigs remains unknown. In
the present study, we found out that HP-PRRSV infection could increase PGE2
production by upregulation of COX-1, and we subsequently characterized the
underlying mechanisms about how HP-PRRSV enhances COX-1 production. PGE2 plays a
critical role in inducing high temperature in hosts during pathogen infections.
Thus, our findings here could help us have a better understanding of HP-PRRSV
pathogenesis.
PMID- 24352470
TI - Kaposi's sarcoma-associated herpesvirus induces the ATM and H2AX DNA damage
response early during de novo infection of primary endothelial cells, which play
roles in latency establishment.
AB - The DNA damage response (DDR) that evolved to repair host cell DNA damage also
recognizes viral DNA entering the nucleus during infections. Here, we
investigated the modulation of DDR signaling during de novo infection of primary
endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV).
Phosphorylation of representative DDR-associated proteins, such as ataxia
telangiectasia mutated (ATM) and H2AX, was induced as early as 30 min (0.5 h)
postinfection and persisted during in vitro KSHV latency. Phosphorylated H2AX
(gammaH2AX) colocalized at 30 min (0.5 h) with the KSHV genome entering the
nuclei. Total H2AX protein levels also increased, and the increase was attributed
to a decrease in degradative H2AX Lys48-linked polyubiquitination with a
concomitant increase in Lys63-linked polyubiquitination that was shown to
increase protein stability. ATM and H2AX phosphorylation and gammaH2AX nuclear
foci were also induced by UV-inactivated KSHV, which ceased at later times of
infection. Inhibition of ATM kinase activity by KU-55933 and H2AX knockdown by
small interfering RNA significantly reduced the expression of the KSHV latency
associated nuclear antigen 1 (LANA-1; ORF73) and LANA-1 nuclear puncta. Knockdown
of H2AX also resulted in a >80% reduction in the nuclear KSHV DNA copy numbers.
Similar results were also observed in ATM-negative cells, although comparable
levels of viral DNA entered ATM-negative and ATM-positive cell nuclei. In
contrast, knockdown of CHK1 and CHK2 did not affect ORF73 expression.
Collectively, these results demonstrate that KSHV induces ATM and H2AX, a
selective arm of the DDR, for the establishment and maintenance of its latency
during de novo infection of primary endothelial cells. IMPORTANCE: Eukaryotic
cells mount a DNA damage response (DDR) to sense and repair different types of
cellular DNA damage. In addition, DDR also recognizes exogenous genetic material,
such as the viral DNA genome entering the nucleus during infections. The present
study was undertaken to determine whether de novo Kaposi's sarcoma-associated
herpesvirus (KSHV) infection modulates DDR. Our results demonstrate that early
during de novo infection of primary endothelial cells, KSHV induces a selective
arm of DDR signaling, such as the ATM kinase and its downstream target, H2AX,
which are essential for KSHV's latent gene expression and the establishment of
latency. These studies suggest that targeting ATM and H2AX could serve as an
attractive strategy to block the establishment of KSHV latent infection and the
associated malignancies.
PMID- 24352471
TI - Divergent antibody subclass and specificity profiles but not protective HLA-B
alleles are associated with variable antibody effector function among HIV-1
controllers.
AB - Understanding the coordination between humoral and cellular immune responses may
be the key to developing protective vaccines, and because genetic studies of long
term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous
control of viral replication, this subject group presents an opportunity to
investigate relationships between arms of the adaptive immune system. Given
evidence suggesting that cellular immunity may play a role in viral suppression,
we sought to determine whether and how the humoral immune response might vary
among controllers. Significantly, Fc-mediated antibody effector functions have
likewise been associated with durable viral control. In this study, we compared
the effector function and biophysical features of HIV-specific antibodies in a
cohort of controllers with and without protective HLA-B alleles in order to
investigate whether there was evidence for multiple paths to HIV-1 control, or
whether cellular and humoral arms of immunity might exhibit coordinated profiles.
However, with the exception of IgG2 antibodies to gp41, HLA status was not
associated with divergent humoral responses. This finding did not result from
uniform antibody responses across subjects, as controllers could be regrouped
according to strong differences in their HIV-specific antibody subclass
specificity profiles. These divergent antibody profiles were further associated
with significant differences in nonneutralizing antibody effector function, with
levels of HIV-specific IgG1 acting as the major distinguishing factor. Thus,
while HLA background among controllers was associated with minimal differences in
humoral function, antibody subclass and specificity profiles were associated with
divergent effector function, suggesting that these features could be used to make
functional predictions. Because these nonneutralizing antibody activities have
been associated with spontaneous viral control, reduced viral load, and
nonprogression in infected subjects and protection in vaccinated subjects,
understanding the specific features of IgGs with potentiated effector function
may be critical to vaccine and therapeutic antibody development. IMPORTANCE: In
this study, we investigated whether the humoral and cellular arms of adaptive
immunity exhibit coordinated or compensatory activity by studying the antibody
response among HIV-1 controllers with different genetic backgrounds.
PMID- 24352472
TI - Hepatitis C virus stimulates low-density lipoprotein receptor expression to
facilitate viral propagation.
AB - Lipids play a crucial role in multiple aspects of hepatitis C virus (HCV) life
cycle. HCV modulates host lipid metabolism to enrich the intracellular milieu
with lipids to facilitate its proliferation. However, very little is known about
the influence of HCV on lipid uptake from bloodstream. Low-density lipoprotein
receptor (LDLR) is involved in uptake of cholesterol rich low-density lipoprotein
(LDL) particles from the bloodstream. The association of HCV particles with
lipoproteins implicates their role in HCV entry; however, the precise role of
LDLR in HCV entry still remains controversial. Here, we investigate the effect of
HCV infection on LDLR expression and the underlying mechanism(s) involved. We
demonstrate that HCV stimulates LDLR expression in both HCV-infected Huh7 cells
and in liver tissue from chronic hepatitis C patients. Fluorescence activated
cell sorting and immunofluorescence analysis revealed enhanced cell surface and
total expression of LDLR in HCV-infected cells. Increased LDLR expression
resulted in the enhanced uptake of lipoprotein particles by HCV-infected cells.
Analysis of LDLR gene promoter identified a pivotal role of sterol-regulatory
element binding proteins (SREBPs), in the HCV-mediated stimulation of LDLR
transcription. In addition, HCV negatively modulated the expression of proprotein
convertase subtilisin/kexin type 9 (PCSK9), a protein that facilitates LDLR
degradation. Ectopic expression of wild-type PCSK9 or gain-of-function PCSK9
mutant negatively affected HCV replication. Overall, our results demonstrate that
HCV regulates LDLR expression at transcriptional and posttranslational level via
SREBPs and PCSK9 to promote lipid uptake and facilitate viral proliferation.
IMPORTANCE: HCV modulates host lipid metabolism to promote enrichment of lipids
in intracellular environment, which are essential in multiple aspects of HCV life
cycle. However, very little is known about the influence of HCV on lipid uptake
from the bloodstream. LDLR is involved in uptake of cholesterol rich lipid
particles from bloodstream. In this study, we investigated the effect of HCV on
LDLR expression and the underlying mechanism triggered by the virus to modulate
LDLR expression. Our observations suggest that HCV upregulates LDLR expression at
both the protein and the transcript levels and that this upregulation likely
contributes toward the uptake of serum lipids by infected hepatocytes. Abrogation
of HCV-mediated upregulation of LDLR inhibits serum lipid uptake and thereby
perturbs HCV replication. Overall, our findings highlight the importance of serum
lipid uptake by infected hepatocytes in HCV life cycle.
PMID- 24352473
TI - Effect of microtubule disruption on neuronal spread and replication of
demyelinating and nondemyelinating strains of mouse hepatitis virus in vitro.
AB - The isogenic host attachment spike protein recombinant demyelinating strain of
mouse hepatitis virus (MHV) (RSA59) and the nondemyelinating strain (RSMHV2)
differ in their abilities to infect distinct types of neural cells, spread from
cell to cell, and induce subsequent demyelination and axonal loss. The
differential demyelination properties of RSA59 and RSMHV2 may be a function of
spike protein-mediated neuronal transport. Disruption of microtubules with
colchicine and vinblastine significantly blocks neuronal transport and reduces
the replication of RSA59, whereas RSMHV2 remains unaffected.
PMID- 24352474
TI - Significant differences in nurses' knowledge of basic wound management -
implications for treatment.
AB - Wounds represent a growing healthcare problem due to an aging population. Nurses
play a key role in wound management and their theoretical understanding of basic
wound management may be expected to influence the quality of wound therapy
fundamentally. In this study, we evaluated the level of knowledge of wound
management in 136 Danish nurses working in 3 different settings: advanced wound
care clinics, home care and general hospital departments. We found that hospital
nurses had less theoretical knowledge than home care nurses and nurses working at
advanced wound care clinics. We also found that the length of experience
(adjusted for workplace and education) did not have any impact on nurses'
knowledge. Nurses' knowledge of clinical investigations was consistently lower
than their knowledge of therapy and clinical symptoms. This study provides
benchmarking information about the current status of wound management in Denmark
and suggests how improvements might be achieved.
PMID- 24352475
TI - Conversion of fusaric acid to Fusarinol by Aspergillus tubingensis: a
detoxification reaction.
AB - The fungus Fusarium oxysporum causes wilt diseases of plants and produces a
potent phytotoxin fusaric acid (FA), which is also toxic to many microorganisms.
An Aspergillus tubingensis strain with high tolerance to FA was isolated from
soil and designated as CDRAt01. HPLC analysis of culture filtrates from A.
tubingensis isolate CDRAt01 grown with the addition of FA indicated the formation
of a metabolite over time that was associated with a decrease of FA. Spectral
analysis and chemical synthesis confirmed the compound as 5-butyl-2
pyridinemethanol, referred to here as fusarinol. The phytotoxicity of fusarinol
compared to FA was measured by comparing necrosis induced in cotton (Gossypium
hirsutum L. cv. Coker 312) cotyledons. Fusarinol was significantly less
phytotoxic than FA. Therefore, the A. tubingensis strain provides a novel
detoxification mechanism against FA which may be utilized to control Fusarium
wilt.
PMID- 24352477
TI - Exchange interactions in [2 * 2] Cu(II) grids: on the reliability of the fitting
spin models.
AB - This paper reports a theoretical analysis of the electronic structure and
magnetic properties of a ferromagnetic Cu(II) [2 * 2] grid. The calculations
confirm a quintet (S = 2) ground state and an energy-level distribution of the
magnetic states in accordance with Heisenberg behaviour. The whole set of first-
and second-neighbour magnetic coupling constants has been evaluated, all in
agreement with the structure and arrangement of the Cu 3dx(2) - y(2) magnetic
orbitals. The results indicate that the dominant interaction in the system is the
ferromagnetic coupling between the nearest Cu sites. The calculated J values
suggest a C(2v) spin-spin interaction pattern, instead of the D(4h) model
employed in the magnetic data fit. However, both spin models provide similar
plots of the thermal dependence of the susceptibility and magnetic moment data.
This study highlights the fact that the spin models resulting from the fittings
can be just effective models, capable of correctly reproducing the macroscopic
properties, although not always in accordance with the microscopic interactions
governing these properties.
PMID- 24352476
TI - Innate immune memory: implications for development of pediatric immunomodulatory
agents and adjuvanted vaccines.
AB - Unique features of immunity early in life include a distinct immune system
particularly reliant on innate immunity, with weak T helper (Th)1-polarizing
immune responses, and impaired responses to certain vaccines leading to a
heightened susceptibility to infection. To these important aspects, we now add an
increasingly appreciated concept that the innate immune system displays
epigenetic memory of an earlier infection or vaccination, a phenomenon that has
been named "trained immunity." Exposure of neonatal leukocytes in vitro or
neonatal animals or humans in vivo to specific innate immune stimuli results in
an altered innate immune set point. Given the particular importance of innate
immunity early in life, trained immunity to early life infection and/or
immunization may play an important role in modulating both acute and chronic
diseases.
PMID- 24352479
TI - Role of vitamin D in flare ups of rheumatoid arthritis.
AB - INTRODUCTION: Rheumatoid arthritis (RA) is one of the most prevalent autoimmune
diseases worldwide. Some researchers have suggested that the serum vitamin D (Vit
D) level may relate to disease activity. The current study was designed to
identify the correlation between vitamin D prescription and prevention of
relapses in rheumatoid arthritis. PATIENTS AND METHOD: A double blinded,
randomized controlled trial study was performed using 80 RA patients. RA was
controlled and patients were in remission during the past 2 months. Serum level
of Vit D in the studied patients was below 30 ng/dl. Patients were randomly
allocated to receive Vit D or placebo. In the 6-month follow-up period, the
Disease Activity Score 28 (DAS28) was used in case of relapses as an index of RA
activity to compare the two groups. RESULTS: The flare rate was not different
between two groups (p > 0.05). The odds ratio of the rate of decline in patients
of the trial group compared with the control group was 1.17 (not significant; p >
0.05). The mean DAS28 between the two patient groups was not significant (p >
0.05). CONCLUSION: A low Vit D level was not identified to be a risk factor for
RA severity or flare ups; however, although not statistically significant, Vit D
treatment might be clinically effective. Further studies are needed with more
emphasis on the issue of cost effectiveness and clinical importance to provide
more information.
PMID- 24352481
TI - Multi-core CPU or GPU-accelerated Multiscale Modeling for Biomolecular Complexes.
AB - Multi-scale modeling plays an important role in understanding the structure and
biological functionalities of large biomolecular complexes. In this paper, we
present an efficient computational framework to construct multi-scale models from
atomic resolution data in the Protein Data Bank (PDB), which is accelerated by
multi-core CPU and programmable Graphics Processing Units (GPU). A multi-level
summation of Gaus-sian kernel functions is employed to generate implicit models
for biomolecules. The coefficients in the summation are designed as functions of
the structure indices, which specify the structures at a certain level and enable
a local resolution control on the biomolecular surface. A method called
neighboring search is adopted to locate the grid points close to the expected
biomolecular surface, and reduce the number of grids to be analyzed. For a
specific grid point, a KD-tree or bounding volume hierarchy is applied to search
for the atoms contributing to its density computation, and faraway atoms are
ignored due to the decay of Gaussian kernel functions. In addition to density map
construction, three modes are also employed and compared during mesh generation
and quality improvement to generate high quality tetrahedral meshes: CPU
sequential, multi-core CPU parallel and GPU parallel. We have applied our
algorithm to several large proteins and obtained good results.
PMID- 24352480
TI - PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet
functional responses.
AB - 3-phosphoinositide-dependent protein kinase 1 (PDK1), a member of the protein A,G
and C (AGC) family of proteins, is a Ser/Thr protein kinase that can
phosphorylate and activate other protein kinases from the AGC family, including
Akt at Thr308, all of which play important roles in mediating cellular responses.
The functional role of PDK1 or the importance of phosphorylation of Akt on Thr308
for its activity has not been investigated in human platelets. In this study, we
tested two pharmacological inhibitors of PDK1, BX795 and BX912, to assess the
role of Thr308 phosphorylation on Akt. PAR4-induced phosphorylation of Akt on
Thr308 was inhibited by BX795 without affecting phosphorylation of Akt on Ser473.
The lack of Thr308 phosphorylation on Akt also led to the inhibition of PAR4
induced phosphorylation of two downstream substrates of Akt, viz. GSK3beta and
PRAS40. In vitro kinase activity of Akt was completely abolished if Thr308 on Akt
was not phosphorylated. BX795 caused inhibition of 2-MeSADP-induced or collagen
induced aggregation, ATP secretion and thromboxane generation. Primary
aggregation induced by 2-MeSADP was also inhibited in the presence of BX795. PDK1
inhibition also resulted in reduced clot retraction indicating its role in
outside-in signalling. These results demonstrate that PDK1 selectively
phosphorylates Thr308 on Akt thereby regulating its activity and plays a positive
regulatory role in platelet physiological responses.
PMID- 24352482
TI - Hydroxyethyl starch: putting patient safety first.
PMID- 24352484
TI - The impact of patient positioning on pressure ulcers in patients with severe
ARDS: results from a multicentre randomised controlled trial on prone
positioning.
AB - PURPOSE: Placing patients with severe acute respiratory distress syndrome (ARDS)
in the prone position has been shown to improve survival as compared to the
supine position. However, a higher frequency of pressure ulcers has been reported
in patients in the prone position. The objective of this study was to verify the
impact of prone positioning on pressure ulcers in patients with severe ARDS.
METHODS: This was an ancillary study of a prospective multicentre randomised
controlled trial in patients with severe ARDS in which the early application of
long prone-positioning sessions was compared to supine positioning in terms of
mortality. Pressure ulcers were assessed at the time of randomisation, 7 days
later and on discharge from the intensive care unit (ICU), using the four-stage
Pressure Ulcers Advisory Panel system. The primary end-point was the incidence
(with reference to 1,000 days of invasive mechanical ventilation or 1,000 days of
ICU stay) of new patients with pressure ulcers at stage 2 or higher from
randomisation to ICU discharge. RESULTS: At randomisation, of the 229 patients
allocated to the supine position and the 237 patients allocated to the prone
position, the number of patients with pressure ulcers was not significantly
different between groups. The incidence of new patients with pressure ulcers from
randomisation to ICU discharge was 20.80 and 14.26/1,000 days of invasive
mechanical ventilation (P = 0.061) and 13.92 and 7.72/1,000 of ICU days (P =
0.002) in the prone and supine groups, respectively. Position group [odds ratio
(OR) 1.5408, P = 0.0653], age >60 years (OR 1.5340, P = 0.0019), female gender
(OR 0.5075, P = 0.019), body mass index of >28.4 kg/m(2) (OR 1.9804, P = 0.0037),
and a Simplified Acute Physiology Score II at inclusion of >46 (OR 1.2765, P =
0.3158) were the covariates independently associated to the acquisition of
pressure ulcers. CONCLUSION: In patients with severe ARDS, prone positioning was
associated with a higher frequency of pressure ulcers than the supine position.
Prone positioning improves survival in patients with severe ARDS and, therefore,
survivors who received this intervention had a greater likelihood of having
pressure ulcers documented as part of their follow-up. There are risk groups for
the development of pressure ulcers in severe ARDS, and these patients need
surveillance and active prevention.
PMID- 24352485
TI - Light levels of sedation and DSM-5 criteria for delirium.
PMID- 24352486
TI - Impact of computerized physician order entry (CPOE) on PICU prescribing errors.
PMID- 24352487
TI - Arterial blood pressure changes induced by acceleration during mobile intensive
care unit patient transport are not patient related: beware of misinterpretation.
PMID- 24352488
TI - eComment. Spinal cord protection during thoracoabdominal aneurysm repair.
PMID- 24352489
TI - eReply. Spinal cord protection during thoracoabdominal aneurysm repair.
PMID- 24352490
TI - eComment. Repair versus mitral replacement in patients undergoing concomitant
aortic valve replacement.
PMID- 24352491
TI - eComment. Laser application on lung parenchyma.
PMID- 24352492
TI - eComment. New frontiers of pulmonary resections: possible usefulness of
autologous adipose mesenchymal cells.
PMID- 24352493
TI - eComment. Two internal mammary artery grafts are better than one.
PMID- 24352494
TI - eComment. Left ventricular pseudoaneurysm: an attempt of guidelines for the
surgical treatment.
PMID- 24352495
TI - eComment. A paradigm shift in the emergent management of aortobronchial fistula.
PMID- 24352496
TI - eComment. Late complications after aortic coarctation repair.
PMID- 24352497
TI - eComment. Multiple strategies for sternal reconstruction.
PMID- 24352499
TI - An Age-Related Dissociation of Short-Term Memory for Facial Identity and Facial
Emotional Expression.
AB - BACKGROUND: Memory for both facial emotional expression and facial identity was
explored in younger and older adults in 3 experiments using a delayed match-to
sample procedure. METHOD: Memory sets of 1, 2, or 3 faces were presented, which
were followed by a probe after a 3-s retention interval. RESULTS: There was very
little difference between younger and older adults in memory for emotional
expressions, but memory for identity was substantially impaired in the older
adults. DISCUSSION: Possible explanations for spared memory for emotional
expressions include socioemotional selectivity theory as well as the existence of
overlapping yet distinct brain networks for processing of different emotions.
PMID- 24352498
TI - Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac
bundle.
AB - Tissue engineering enables the generation of three-dimensional (3D) functional
cardiac tissue for pre-clinical testing in vitro, which is critical for new drug
development. However, current tissue engineering methods poorly recapitulate the
architecture of oriented cardiac bundles with supporting capillaries. In this
study, we designed a microfabricated bioreactor to generate 3D micro-tissues,
termed biowires, using both primary neonatal rat cardiomyocytes and human
embryonic stem cell (hESC) derived cardiomyocytes. Perfusable cardiac biowires
were generated with polytetrafluoroethylene (PTFE) tubing template, and were
integrated with electrical field stimulation using carbon rod electrodes. To
demonstrate the feasibility of this platform for pharmaceutical testing, nitric
oxide (NO) was released from perfused sodium nitroprusside (SNP) solution and
diffused through the tubing. The NO treatment slowed down the spontaneous beating
of cardiac biowires based on hESC derived cardiomyocytes and degraded the
myofibrillar cytoskeleton of the cardiomyocytes within the biowires. The biowires
were also integrated with electrical stimulation using carbon rod electrodes to
further improve phenotype of cardiomyocytes, as indicated by organized
contractile apparatus, higher Young's modulus, and improved electrical
properties. This microfabricated platform provides a unique opportunity to assess
pharmacological effects on cardiac tissue in vitro by perfusion in a cardiac
bundle model, which could provide improved physiological relevance.
PMID- 24352500
TI - DSPP contains an IRES element responsible for the translation of dentin
phosphophoryn.
AB - The major phosphoprotein in dentin is the aspartic acid and serine-rich protein
called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a
larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been
isolated or detected in dentin extracts. It is now evident that DSPP is a
chimeric protein composed of 3 parts: dentin sialoprotein (DSP), DPP, and dentin
glycoprotein (DGP). Previous reports have suggested that the BMP1 protease is
responsible for processing DSPP. However, unequal amounts of these products are
present in the dentin matrix. Here, we provide evidence for an internal ribosome
entry site in the DSPP gene that directs the synthesis of DPP. This mechanism
would account for unequal amounts of intracellular DSP and DPP. The internal
ribosomal entry site (IRES) activity varied in different cell types, suggesting
the presence of additional regulatory elements during the translational
regulation of DPP. Further, we provide evidence that DPP is transported to the
extracellular matrix (ECM) through exosomes. Using tissue recombination and
lentivirus-mediated gain-of-function approaches, we also demonstrate that DPP is
essential for the formation of well-defined tooth structures with mineralized
dentin matrix.
PMID- 24352502
TI - cis-Urocanic acid as a potential nickel(II) binding molecule in the human skin.
AB - cis-Urocanic acid, a derivative of histidine, is one of the essential components
of human skin. We found that it can bind nickel(II) ions in a pH-dependent
manner, with the dissociation constant in the low millimolar range, as revealed
by potentiometry, and confirmed by isothermal titration calorimetry and UV-vis
spectroscopy. The binding occurs within the physiological skin pH range.
Considering the fact that cis-urocanic acid is present in the human skin in
concentrations as high as millimolar, this molecule may be a physiologically
important player in nickel trafficking in the human organism.
PMID- 24352503
TI - The physical basis of renal fibrosis: effects of altered hydrodynamic forces on
kidney homeostasis.
AB - Healthy kidneys are continuously exposed to an array of physical forces as they
filter the blood: shear stress along the inner lumen of the tubules, distension
of the tubular walls in response to changing fluid pressures, and bending moments
along both the cilia and microvilli of individual epithelial cells that comprise
the tubules. Dysregulation of kidney homeostasis via underlying medical
conditions such as hypertension, diabetes, or glomerulonephritis fundamentally
elevates the magnitudes of each principle force in the kidney and leads to
fibrotic scarring and eventual loss of organ function. The purpose of this review
is to summarize the progress made characterizing the response of kidney cells to
pathological levels of mechanical stimuli. In particular, we examine important,
mechanically responsive signaling cascades and explore fundamental changes in
renal cell homeostasis after cyclic strain or fluid shear stress exposure.
Elucidating the effects of these disease-related mechanical imbalances on
endogenous signaling events in kidney cells presents a unique opportunity to
better understand the fibrotic process.
PMID- 24352501
TI - Simvastatin inhibits LPS-induced alveolar bone loss during metabolic syndrome.
AB - Studies in recent years have shown a positive relationship between metabolic
syndrome (MS) and periodontal disease (PD). Given that patients with MS take
statins to reduce cholesterol, and statins also have anti-inflammatory effects,
it is important to determine if statin intake hinders the progression of MS
associated PD. In this study, PD was induced in Zucker fat rats (ZFRs), an animal
model for MS, and in control lean rats by periodontal injection of
Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), while simvastatin
was given to some of the rats via gavage. After 4 wk of treatment, alveolar bone
loss was determined by micro-computed tomography. To explore the underlying
mechanisms, we determined the effect of simvastatin on tissue inflammation and
the expression of molecules involved in osteoclastogenesis. Results showed that
while bone loss was increased by LPS in both ZFRs and the control lean rats, it
was significantly more in the former than the latter. Simvastatin effectively
alleviated bone loss in both ZFRs and the control rats. Results also showed that
LPS stimulated leukocyte tissue infiltration and expression of molecules for
osteoclastogenesis, but simvastatin significantly modulated the stimulation. This
study demonstrated that simvastatin inhibited LPS-induced alveolar bone loss and
periodontal tissue inflammation in rats with MS.
PMID- 24352504
TI - Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus
independently of the sodium-chloride cotransporter.
AB - Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI).
Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in
Li-NDI. The paradoxical antidiuretic action of HCTZ in Li-NDI is generally
attributed to increased sodium and water uptake in proximal tubules as a
compensation for increased volume loss due to HCTZ inhibition of the Na-Cl
cotransporter (NCC), but alternative actions for HCTZ have been suggested. Here,
we investigated whether HCTZ exerted an NCC-independent effect in Li-NDI. In
polarized mouse cortical collecting duct (mpkCCD) cells, HCTZ treatment
attenuated the Li-induced downregulation of aquaporin-2 (AQP2) water channel
abundance. In these cells, amiloride reduces cellular Li influx through the
epithelial sodium channel (ENaC). HCTZ also reduced Li influx, but to a lower
extent. HCTZ increased AQP2 abundance on top of that of amiloride and did not
affect the ENaC-mediated transcellular voltage. MpkCCD cells did not express NCC
mRNA or protein. These data indicated that in mpkCCD cells, HCTZ attenuated
lithium-induced downregulation of AQP2 independently of NCC and ENaC. Treatment
of Li-NDI NCC knockout mice with HCTZ revealed a significantly reduced urine
volume, unchanged urine osmolality, and increased cortical AQP2 abundance
compared with Li-treated NCC knockout mice. HCTZ treatment further resulted in
reduced blood Li levels, creatinine clearance, and alkalinized urinary pH. Our in
vitro and in vivo data indicate that part of the antidiuretic effect of HCTZ in
Li-NDI is NCC independent and may involve a tubuloglomerular feedback response
mediated reduction in glomerular filtration rate due to proximal tubular carbonic
anhydrase inhibition.
PMID- 24352505
TI - Effect of chronic metabolic acidosis on bone density and bone architecture in
vivo in rats.
AB - Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass
based on its reported in vitro inhibition of bone mineralization, bone formation,
or stimulation of bone resorption, but such data, in the absence of other
disorders, have not been reported. CMA also results in negative nitrogen balance,
which might decrease skeletal muscle mass. This study analyzed the net in vivo
effects of CMA's cellular and physicochemical processes on bone turnover,
trabecular and cortical bone density, and bone microarchitecture using both
peripheral quantitative computed tomography and MUCT. CMA induced by NH4Cl
administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats
resulted in stable CMA (mean Delta[HCO3(-)]p = 10 mmol/l). CMA decreased plasma
osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total
volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal
+2.1 +/- 0.9% vs. intact acidosis -3.6 +/- 1.2%, P < 0.001), an effect
attributable to a decrease in cortical thickness and, thus, cortical bone mass
(no significant effect on cancellous vBMD, week 10) attributed to an increase in
endosteal bone resorption (nominally increased endosteal circumference).
Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6
and 10 wk, associated with a decrease in trabecular number. CMA significantly
decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In
conclusion, chronic metabolic acidosis induces a large decrease in cortical bone
mass (a prime determinant of bone fragility) in intact and OVX rats and impairs
bone microarchitecture characterized by a decrease in trabecular number.
PMID- 24352506
TI - Facile and scalable synthesis of Ti5Si3 nanoparticles in molten salts for metal
matrix nanocomposites.
AB - We report a novel synthesis of Ti5Si3 nanoparticles (NPs) via the magnesio
reduction of TiO2 NPs and SiO2 in eutectic LiCl-KCl molten salts at 700 degrees
C. The Ti5Si3 particle size (~25 nm) is confined to the nanoscale due to the
partial dissolution of Mg and silica in the molten salts and a subsequent
heterogeneous reduction on the surface of the TiO2 NPs.
PMID- 24352508
TI - The proportion of lymphocytic inflammation with CD123-positive cells in lupus
erythematous profundus predict a clinical response to treatment.
AB - Lupus erythematosus profundus is a rare inflammatory disorder of subcutaneous fat
in patients with lupus ery-thematosus. Previous reports suggested that
plasmacytoid dendritic cells, which expressed CD123 and CD303 antigens, play a
central proinflammatory role in the patho-genesis of lupus erythematosus. To find
the factors that determine the response to treatment, we analysed 23 skin
specimens from the patients with lupus erythematosus profundus. The patients with
considerable lymphocytic inflammation with high percentages of CD123+ cells in
dermis and subcutaneous fat significantly responded to the systemic
corticosteroid therapies. On the other hand, the patients with minor lymphocytic
inflammation with low percentages of CD123+ cells showed poor response to
treatments. The mean percentage of CD123+ cells in patients who showed good
response to therapy was significantly higher than those that showed poor response
(p = 0.027). These results suggest that the clinical response to treatment of
lupus erythematosus profundus could be predicted from the histological features.
PMID- 24352507
TI - Adenosine is required for sustained inflammasome activation via the A2A receptor
and the HIF-1alpha pathway.
AB - Inflammasome pathways are important in chronic diseases; however, it is not known
how the signalling is sustained after initiation. Inflammasome activation is
dependent on stimuli such as lipopolysaccharide (LPS) and ATP that provide two
distinct signals resulting in rapid production of interleukin (IL)-1beta, with
the lack of response to repeat stimulation. Here we report that adenosine is a
key regulator of inflammasome activity, increasing the duration of the
inflammatory response via the A(2A) receptor. Adenosine does not replace signals
provided by stimuli such as LPS or ATP but sustains inflammasome activity via a
cAMP/PKA/CREB/HIF-1alpha pathway. In the setting of the lack of IL-1beta
responses after previous exposure to LPS, adenosine can supersede this
tolerogenic state and drive IL-1beta production. These data reveal that
inflammasome activity is sustained, after initial activation, by A(2A) receptor
mediated signalling.
PMID- 24352509
TI - Investigation of four novel male androgenetic alopecia susceptibility loci: no
association with female pattern hair loss.
AB - Female pattern hair loss (FPHL) is a common hair loss disorder in women and has a
complex mode of inheritance. The etiopathogenesis of FPHL is largely unknown;
however, it is hypothesized that FPHL and male pattern baldness [androgenetic
alopecia (AGA)] share common genetic susceptibility alleles. Our recent findings
indicate that the major AGA locus, an X-chromosome region containing the androgen
receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common
genetic factor underlying both early-onset FPHL and AGA. This gives further
support for the widespread assumption of shared susceptibility loci for FPHL and
AGA. However, we could not demonstrate association of further AGA risk loci,
including 20p11, 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, and 18q21.1, with
FPHL. Interestingly, a recent study identified four novel AGA risk loci in
chromosomal regions 2q35, 3q25.1, 5q33.3, and 12p12.1. In particular, the 2q35
locus and its gene WNT10A point to an as-yet unknown involvement of the WNT
signaling pathway in AGA. We hypothesized that the novel loci and thus also the
WNT signaling may have a role in the etiopathogenesis of FPHL and therefore
examined the role of these novel AGA risk loci in our FPHL samples comprising 440
German and 145 UK affected patients, 500 German unselected controls (blood
donors), and 179 UK supercontrols. Patients and controls were genotyped for the
top two single nucleotide polymorphisms at each of the four AGA loci. However,
none of the genotyped variants displayed any significant association. In
conclusion, the results of this study provide no support for the hypothesis that
the novel AGA loci influence susceptibility to FPHL.
PMID- 24352510
TI - Identifying emergent social networks at a federally qualified health center-based
farmers' market.
AB - Identifying potential mechanisms connecting farmers' market interventions with
health, economic, and community outcomes could inform strategies for addressing
health disparities. The present study used social network theory to guide the in
depth examination of naturally occurring social interactions at a farmers' market
located at a federally qualified health center located in a rural, low-income
community. Trained observers recorded 61 observation logs at the market over 18
weeks. Thematic analysis revealed a range of actors and nonhuman facilitators
instrumental to the farmers' market context. These actors connected with one
another for communication and relationship development, economic and financial
exchange, education, resource sharing, community ownership of the farmers'
market, and conflict resolution. These interactions provided opportunities for
social networks to develop among attendees, which may have facilitated the
acquisition of social supports related to improved health, economic and community
outcomes. Results provide insight into the role social networks may play in
mediating the relationship between a farmers' market intervention and individual
benefits. Findings also contribute to defining the typology of social networks,
which may further disentangle the complex relationships between social networks
and health outcomes. Future research should identify strategies for purposefully
targeting social networks as a way to reduce diet-related health disparities.
PMID- 24352512
TI - Innovation in safety, and safety in innovation.
PMID- 24352511
TI - Thrombin generation using the calibrated automated thrombinoscope to assess
reversibility of dabigatran and rivaroxaban.
AB - The new direct-acting anticoagulants such as dabigatran and rivaroxaban are
usually not monitored but may be associated with haemorrhage, particularly where
renal impairment occurs. They have no effective "antidotes". We studied 17
patients receiving dabigatran 150 mg twice daily for non-valvular atrial
fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention
of deep venous thrombosis after hip or knee replacement surgery. We assessed the
effect of these drugs on commonly used laboratory tests and Calibrated Automated
Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole
blood citrated patient samples using thromboelastography on the TEG and the
ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex
concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and
recombinant activated factor VII (rVIIa) were tested by reversal of abnormal
thrombin generation using the CAT. Concentrations added ex vivo were chosen to
reflect doses normally given in vivo. Dabigatran significantly increased the
dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It
significantly reduced the endogenous thrombin potential (ETP) and reduced the
peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters
but did increase the lag time and reduce ETP and peak height of the CAT. For both
drugs, these parameters were significantly and meaningfully corrected by PCC and
FEIBA and to a lesser but still significant extent by rFVIIa. These results may
be useful in devising a reversal strategy in patients but clinical experience
will be needed to verify them.
PMID- 24352513
TI - An idiographic approach to estimating models of dyadic interactions with
differential equations.
AB - We present an idiographic approach to modeling dyadic interactions using
differential equations. Using data representing daily affect ratings from
romantic relationships, we examined several models conceptualizing different
types of dyadic interactions. We fitted each model to each of the dyads and the
resulting AICc values were used to classify the most likely configuration of
interaction for each dyad. Additionally, the AICc from the different models were
used in parameter averaging across models. Averaged parameters were used in
models involving predictors of relationship dynamics, as indexed by these
parameters, as well as models wherein the parameters predicted distal outcomes of
the dyads such as relationship satisfaction and status. Results indicated that,
within our sample, the most likely interaction style was that of independence,
without evidence of emotional interrelations between the two individuals in the
couple. Attachment-related avoidance and anxiety showed significant relations
with model parameters, such that ideal levels of affect for males were negatively
influenced by higher levels of avoidance from their partner while their own
levels of anxiety had positive effects on their levels of dyadic coregulation.
For females coregulation was negatively influenced by both time in the
relationship and their partner's level of avoidance. Analysis involving distal
outcomes showed modest influences from the individual's level of ideal affect.
PMID- 24352514
TI - Rasch Trees: A New Method for Detecting Differential Item Functioning in the
Rasch Model.
AB - A variety of statistical methods have been suggested for detecting differential
item functioning (DIF) in the Rasch model. Most of these methods are designed for
the comparison of pre-specified focal and reference groups, such as males and
females. Latent class approaches, on the other hand, allow the detection of
previously unknown groups exhibiting DIF. However, this approach provides no
straightforward interpretation of the groups with respect to person
characteristics. Here, we propose a new method for DIF detection based on model
based recursive partitioning that can be considered as a compromise between those
two extremes. With this approach it is possible to detect groups of subjects
exhibiting DIF, which are not pre-specified, but result from combinations of
observed covariates. These groups are directly interpretable and can thus help
generate hypotheses about the psychological sources of DIF. The statistical
background and construction of the new method are introduced by means of an
instructive example, and extensive simulation studies are presented to support
and illustrate the statistical properties of the method, which is then applied to
empirical data from a general knowledge quiz. A software implementation of the
method is freely available in the R system for statistical computing.
PMID- 24352515
TI - Modeling Viewpoint Shifts in Probabilistic Choice.
AB - A number of mathematical models for overcoming intransitive choice have been
proposed and tested in the literature of decision theory. This article presents
the development of a new stochastic choice model based on multidimensional
scaling. This allows decision-makers to have multiple viewpoints, whereas current
multidimensional scaling models are based on the assumption that a subject or
group of subjects has only one viewpoint. The implication of our model is that
subjects make an intransitive choice because they are able to shift their
viewpoint. This paper also presents the maximum likelihood estimation of the
proposed model, and reanalyzes Tversky's gamble experiment data.
PMID- 24352516
TI - A cubic luminescent graphene oxide functionalized Zn-based metal-organic
framework composite for fast and highly selective detection of Cu(2+) ions in
aqueous solution.
AB - In this work, a graphene oxide functionalized Zn-based metal-organic framework
(ZnMOF) was synthesised under a one-pot condition. This ZnMGO composite had high
luminescence and good water dispersibility. The luminescence of the aqueous ZnMGO
composite was efficiently and selectively quenched by Cu(2+) ions through
interactions between Cu(2+) and the ligand. The detection limit was measured at
concentrations as low as 1.00 MUM. This robust ZnMGO composite demonstrated a
fast response and high sensitivity (Ksv = 3.07 * 10(4) M(-1)) for Cu(2+) ions in
aqueous solution. Moreover, the possible luminescence mechanism in terms of
energy migration or electron transfer was further explored, and the quenching
mechanism was discovered to be based on the collapse of the crystal structure
with the help of various characterizations. Remarkably, it is the first time that
this excellent ability possessed by the ZnMGO composite has been used to rapidly
detect Cu(2+) ions in aqueous solution. The work does not only contribute to
extend the potential application of ZnMGO composites, but it also aims to make a
contribution within the biological sciences.
PMID- 24352517
TI - Special edition of Amino Acids of selected papers from the eleventh international
symposium on the Maillard reaction, September 16-20, 2012.
PMID- 24352518
TI - Se-(2-aminoalkyl)selenocysteines as biochemical redox agents. A tool to contrast
cell injury induced by aflatoxin B1 in HepG2 cells.
AB - Se-(2-aminoalkyl)selenocysteines were shown to have a chemoprotective activity
towards HepG2 cells, contrasting the cell damage of aflatoxin B1. The results of
this study suggest that our newly synthesized seleno-diamino acids are apparently
endowed with a potent protective potential against cell damage caused by AFB1
similar to, or even higher than, that exerted by the reference compound Se-Me
SeCys. The protective effect does not seem to be absolute, i.e., merely
determined by the presence of the chalcogen atom, but rather strictly related to
the molecular structure of the new compounds tested. From this point of view, Se
(2-aminoalkyl)selenocysteines may represent a new class of biochemical redox
agents fruitfully exploitable to contrast aflatoxin toxicity, at the same time a
sound medical application and an economically relevant agricultural issue.
PMID- 24352520
TI - Missense mutations in plakophilin-2 cause sodium current deficit and associate
with a Brugada syndrome phenotype.
AB - BACKGROUND: Brugada syndrome (BrS) primarily associates with the loss of sodium
channel function. Previous studies showed features consistent with sodium current
(INa) deficit in patients carrying desmosomal mutations, diagnosed with
arrhythmogenic cardiomyopathy (or arrhythmogenic right ventricular
cardiomyopathy). Experimental models showed correlation between the loss of
expression of desmosomal protein plakophilin-2 (PKP2) and reduced INa. We
hypothesized that PKP2 variants that reduce INa could yield a BrS phenotype, even
without overt structural features characteristic of arrhythmogenic right
ventricular cardiomyopathy. METHODS AND RESULTS: We searched for PKP2 variants in
the genomic DNA of 200 patients with a BrS diagnosis, no signs of arrhythmogenic
cardiomyopathy, and no mutations in BrS-related genes SCN5A, CACNa1c, GPD1L, and
MOG1. We identified 5 cases of single amino acid substitutions. Mutations were
tested in HL-1-derived cells endogenously expressing NaV1.5 but made deficient in
PKP2 (PKP2-KD). Loss of PKP2 caused decreased INa and NaV1.5 at the site of cell
contact. These deficits were restored by the transfection of wild-type PKP2, but
not of BrS-related PKP2 mutants. Human induced pluripotent stem cell
cardiomyocytes from a patient with a PKP2 deficit showed drastically reduced INa.
The deficit was restored by transfection of wild type, but not BrS-related PKP2.
Super-resolution microscopy in murine PKP2-deficient cardiomyocytes related INa
deficiency to the reduced number of channels at the intercalated disc and
increased separation of microtubules from the cell end. CONCLUSIONS: This is the
first systematic retrospective analysis of a patient group to define the
coexistence of sodium channelopathy and genetic PKP2 variations. PKP2 mutations
may be a molecular substrate leading to the diagnosis of BrS.
PMID- 24352521
TI - Association between plasma triglycerides and high-density lipoprotein cholesterol
and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a
global case-control study in 13 countries.
AB - BACKGROUND: Microvascular renal and retinal diseases are common major
complications of type 2 diabetes mellitus. The relation between plasma lipids and
microvascular disease is not well established. METHODS AND RESULTS: The case
subjects were 2535 patients with type 2 diabetes mellitus with an average
duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy.
The case subjects were matched for diabetes mellitus duration, age, sex, and low
density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes
mellitus who did not have kidney disease or retinopathy. The study was conducted
in 24 sites in 13 countries. The primary analysis included kidney disease and
retinopathy cases. Matched analysis was performed by use of site-specific
conditional logistic regression in multivariable models that adjusted for
hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein
cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio
increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5
mmol/L (~1 quintile) increase in triglycerides or decreased by a factor of 0.92
(0.88-0.96) for every 0.2 mmol/L (~1 quintile) increase in high-density
lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23
(1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high
density lipoprotein cholesterol. Retinopathy was associated with triglycerides
and high-density lipoprotein cholesterol in matched analysis but not
significantly after additional adjustment. CONCLUSIONS: Diabetic kidney disease
is associated worldwide with higher levels of plasma triglycerides and lower
levels of high-density lipoprotein cholesterol among patients with good control
of low-density lipoprotein cholesterol. Retinopathy was less robustly associated
with these lipids. These results strengthen the rationale for studying
dyslipidemia treatment to prevent diabetic microvascular disease.
PMID- 24352522
TI - Pharmacometrics and Systems Pharmacology Software Tutorials and Use: Comments and
Guidelines for PSP Contributions.
AB - In addition to methodological Tutorials,(1) CPT:PSP has recently started to
publish software Tutorials.(2,3) Our readership and authors may be wondering what
kind of format or product is expected, and the review of submissions we have
already received prompted several discussions within the PSP Editorial Team. This
editorial reflects on these discussions and summarizes their salient points. It
aims at providing some details about the current vision of CPT:PSP for software
tutorial articles. In addition, it brings some clarity on the topic of what role
commercial software tutorials can have in CPT:PSP and how CPT:PSP tutorials
differ from publications which describe the software itself, as those which can
be found in other computer science journals. Finally, the discussion includes
reproducibility considerations and the general use of commercial and
noncommercial software in CPT:PSP publications. We hope our thoughts, and
especially a stated requirement to publish user input to the software to aid in
reproducibility, will help in guiding our authors and will stimulate healthy
debate among our readers about the evolving nature of our science, how it can be
facilitated using software and associated databases as a conduit, and what role
this journal can play in fostering both the best modeling and simulation
practices and the best scientific approaches to computational modeling, to bring
the advantages of modeling and simulation to all regular practitioners, and not
to just a (self) selected few.
PMID- 24352523
TI - Reduced blood loss after intra-articular tranexamic acid injection during total
knee arthroplasty: a meta-analysis of the literature.
AB - PURPOSE: The purpose of the study is to conduct a meta-analysis of randomized,
controlled trials evaluating the efficacy and safety of intra-articular injection
of tranexamic acid (TXA) for reducing blood loss and transfusion in patients
undergoing total knee arthroplasty (TKA). METHODS: A meta-analysis was conducted
of RCTs published before March 2013, identified from the PubMed, EMBase, Cochrane
library, ScienceDirect, and other databases. Two independent reviewers assessed
the methodological quality of the studies and performed data extraction. Mean
difference in blood loss and blood transfusions, risk ratios of transfusion
rates, and deep vein thrombosis (DVT) incidence in the TXA-treated group versus
placebo group were pooled from the included studies. Data were analysed using
Stata 11.0 software. RESULTS: Six studies were included, with a total sample size
of 647 patients. The use of TXA significantly reduced total blood loss (mean
difference: -344.96; 95% confidence interval (CI) -401.20 to -239.68; P < 0.01)
and the proportion of patients requiring blood transfusions (risk ratios, 0.28;
95% CI: 0.19-0.42; P < 0.01). There were no significant differences in the
incidence of DVT, pulmonary embolism, or other complications between the study
groups. CONCLUSIONS: The present meta-analysis indicated that intra-articular
injection of TXA in patients undergoing TKA may reduce total blood loss and the
need for blood transfusions, particularly when a high dosage of TXA is used (>=30
mg/ml), without any increase in the risk of post-operative DVT. LEVEL OF
EVIDENCE: II.
PMID- 24352524
TI - Genetic counselors' experience with cell-free fetal DNA testing as a prenatal
screening option for aneuploidy.
AB - First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been
used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its
potential to revolutionize prenatal genetic testing as a non-invasive screening
tool. Although this technological advancement is exciting and has certain medical
applications, it has been unclear how it will be implemented in a clinical
setting. Genetic counselors will likely be instrumental in answering that
question, but to date, there is no published research regarding prenatal
counselors' implementation of and experiences with cffDNA testing. We developed a
67 question survey to gather descriptive information from counselors regarding
their personal opinions, experiences, thoughts, and concerns regarding the
validity, usefulness, and implementation of this new technology. A total of 236
individuals completed a portion of the survey; not all respondents answered all
questions. Qualitative questions complemented quantitative survey items, allowing
respondents to voice their thoughts directly. Results indicate that counselors
value cffDNA testing as a screening option but are concerned regarding how some
obstetricians and patients make use of this testing. Further results, discussion,
and practice implications are presented.
PMID- 24352525
TI - Parser Combinators: a Practical Application for Generating Parsers for NMR Data.
AB - Nuclear Magnetic Resonance (NMR) spectroscopy is a technique for acquiring
protein data at atomic resolution and determining the three-dimensional structure
of large protein molecules. A typical structure determination process results in
the deposition of a large data sets to the BMRB (Bio-Magnetic Resonance Data
Bank). This data is stored and shared in a file format called NMR-Star. This
format is syntactically and semantically complex making it challenging to parse.
Nevertheless, parsing these files is crucial to applying the vast amounts of
biological information stored in NMR-Star files, allowing researchers to harness
the results of previous studies to direct and validate future work. One powerful
approach for parsing files is to apply a Backus-Naur Form (BNF) grammar, which is
a high-level model of a file format. Translation of the grammatical model to an
executable parser may be automatically accomplished. This paper will show how we
applied a model BNF grammar of the NMR-Star format to create a free, open-source
parser, using a method that originated in the functional programming world known
as "parser combinators". This paper demonstrates the effectiveness of a
principled approach to file specification and parsing. This paper also builds
upon our previous work [1], in that 1) it applies concepts from Functional
Programming (which is relevant even though the implementation language, Java, is
more mainstream than Functional Programming), and 2) all work and accomplishments
from this project will be made available under standard open source licenses to
provide the community with the opportunity to learn from our techniques and
methods.
PMID- 24352526
TI - Saddling up copper - new twists on a metallo-wheel.
AB - A unique octanuclear copper(II) cluster with a saddle-shaped structural topology
has been prepared from a large, flexible polydentate ligand comprising a 4,4'
bipyridine linker bearing four pendant pyrazolate heterocycles.
PMID- 24352527
TI - Modulation of GSH with exogenous agents leads to changes in glyoxalase 1 enzyme
activity in VL-17A cells exposed to chronic alcohol plus high glucose.
AB - Gluthathione (GSH) is a major cellular antioxidant. The present study utilizing
VL-17A cells exposed to chronic alcohol plus high glucose investigated the
changes in oxidative stress, toxicity, and glyoxalase 1 activity as a
detoxification pathway due to changes in GSH level through GSH supplementation
with N-acetyl cysteine (NAC) or ursodeoxycholic acid (UDCA) and its depletion
through buthionine sulfoximine (BSO) or diethyl maleate (DEM). Glyoxalase 1 plays
an important role in detoxification of methylglyoxal which is formed as a
precursor of advanced glycated end products formed due to high glucose mediated
oxidative stress. Significant changes in glyoxalase 1 activity utilizing
methylglyoxal or glyoxal as substrates occurred with NAC or UDCA or BSO or DEM
supplementation in chronic alcohol plus high glucose treated VL-17A cells. NAC or
UDCA administration in chronic alcohol plus high glucose treated VL-17A cells
increased viability and decreased ROS levels, lipid peroxidation and 3
nitrotyrosine adduct formation. Similarly, GSH depletion with BSO or DEM had an
opposite effect on the parameters in chronic alcohol plus high glucose treated VL
17A cells. In conclusion, modulation of GSH with NAC or UDCA or BSO or DEM leads
to significant changes in oxidative stress, glyoxalase 1 enzyme activity and
toxicity in chronic alcohol plus high glucose treated VL-17A cells.
PMID- 24352528
TI - Carbon-14 dynamics in rice: an extension of the ORYZA2000 model.
AB - Carbon-14 ((14)C) is a radionuclide of major interest in nuclear power
production. The Fukushima accident changed the public attitude on the use of
nuclear energy all over the world. In terms of nuclear safety, the need of
quality-assured radiological models was emphasized by many international
organizations, and for models used by decision-makers (i.e. regulatory
environmental models and radiological models), a moderate conservatism,
transparency, relative simplicity and user friendliness are required. Because the
interaction between crops and the environment is complex and regulated by many
feedback mechanisms, however, these requirements are difficult to accomplish. The
present study makes a step forward regarding the development of a robust model
dealing with food contamination after a short-term accidental emission and
considers a single crop species, rice (Oryza sativa), one of the most widely used
rice species. Old and more recent experimental data regarding the carbon dynamics
in rice plants are reviewed, and a well-established crop growth model, ORYZA2000,
is used and adapted in order to assess the dynamics of (14)C in rice after a
short-term exposure to (14)CO(2). Here, the model is used to investigate the role
of the genotype, management and weather on the concentration of radiocarbon at
harvest.
PMID- 24352530
TI - Radiolabelling diverse positron emission tomography (PET) tracers using a single
digital microfluidic reactor chip.
AB - Radiotracer synthesis is an ideal application for microfluidics because only
nanogram quantities are needed for positron emission tomography (PET) imaging.
Thousands of radiotracers have been developed in research settings but only a few
are readily available, severely limiting the biological problems that can be
studied in vivo via PET. We report the development of an electrowetting-on
dielectric (EWOD) digital microfluidic chip that can synthesize a variety of
(18)F-labeled tracers targeting a range of biological processes by confirming
complete syntheses of four radiotracers: a sugar, a DNA nucleoside, a protein
labelling compound, and a neurotransmitter. The chip employs concentric
multifunctional electrodes that are used for heating, temperature sensing, and
EWOD actuation. All of the key synthesis steps for each of the four (18)F-labeled
tracers are demonstrated and characterized with the chip: concentration of
fluoride ion, solvent exchange, and chemical reactions. The obtained fluorination
efficiencies of 90-95% are comparable to, or greater than, those achieved by
conventional approaches.
PMID- 24352529
TI - Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.)
following mixed exposure to copper and aluminum combined with low-dose gamma
radiation.
AB - Very little is known about the combined effects of low doses of heavy metals and
radiation. However, such "multiple stressor" exposure is the reality in the
environment. In the work reported in this paper, fish were exposed to cobalt 60
gamma irradiation with or without copper or aluminum in the water. Doses of
radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged
from 10 to 80 MUg/L for the same time period. The aluminum dose was 250 MUg/L.
Gills and skin were removed from the fish after exposure and explanted in tissue
culture flasks for investigation of bystander effects of the exposures using a
stress signal reporter assay, which has been demonstrated to be a sensitive
indicator of homeostatic perturbations in cells. The results show complex
synergistic interactions of radiation and copper. Gills on the whole produce more
toxic bystander signals than skin, but the additivity scores show highly variable
results which depend on dose and time of exposure. The impacts of low doses of
copper and low doses of radiation are greater than additive, medium levels of
copper alone have a similar level of effect of bystander signal toxicity to the
low dose. The addition of radiation stress, however, produces clear protective
effects in the reporters treated with skin-derived medium. Gill-derived medium
from the same fish did not show protective effects. Radiation exposure in the
presence of 80 MUg/L led to highly variable results, which due to animal
variation were not significantly different from the effect of copper alone. The
results are stressor type, stressor concentration and time dependent. Clearly co
exposure to radiation and heavy metals does not always lead to simple additive
effects.
PMID- 24352531
TI - Intracranial injection of recombinant stromal-derived factor-1 alpha (SDF-1alpha)
attenuates traumatic brain injury in rats.
AB - OBJECTIVE: This study was conducted to investigate the role of stromal-derived
factor-1 alpha (SDF-1alpha) in a secondary brain injury after traumatic brain
injury (TBI) in rats, and to further elucidate its underlying regulatory
mechanisms. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent TBI for 30
min, and then received intracranial injections of recombinant SDF-1alpha, SDF
1alpha antibody, or saline as a vehicle control. At 24 h after TBI, brain tissues
from the experimental animals were subjected to histology, immunohistochemistry,
quantitative real-time polymerase chain reaction (PCR), enzyme-linked
immunosorbent assay (ELISA), and western blot analyses. RESULTS: TBI-induced
brain edema and blood-brain barrier disruption were ameliorated by post-injury
injections of SDF-1alpha. TBI-induced neuronal degradation and apoptosis,
accompanied by increased cleaved caspase-3, cleaved PARP and Bax, and decreased
Bcl-2 were found to be attenuated by SDF-1alpha injection. Nitric oxide (NO) and
inducible nitric oxide synthase (iNOS) levels decreased in SDF-1alpha treated
animals after TBI. SDF-1alpha repressed inflammatory responses by inhibiting the
expression of pro-inflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6.
However, neutralizing the effect of SDF-1alpha with its antibody abolished these
therapeutic alterations in TBI animals. Importantly, SDF-1alpha attenuated the
brain lesion by affecting the ERK and NF-kappaB signaling pathways after
mechanical head trauma in rats. CONCLUSIONS: SDF-1alpha ameliorates mechanical
trauma-induced pathological changes via its anti-apoptotic and anti-inflammatory
action in the brain.
PMID- 24352532
TI - Resident- and Facility-Level Predictors of Quality of Life in Long-Term Care.
AB - PURPOSE OF THE STUDY: Although there is substantial research on quality of care
in nursing homes (NH), less is known about what contributes to quality of life
(QOL) for NH residents. This study assesses multiple domains of QOL and examines
facility- and resident-level correlates for different domains. DESIGN AND
METHODS: Data come from (a) self-reported resident interviews using a
multidimensional measure of QOL; (b) resident clinical data from the Minimum Data
Set; and (c) facility-level characteristics from Minnesota Department of Human
Services. We used factor analysis to confirm domains of QOL, and then employed
cross-sectional hierarchical linear modeling to identify significant resident-
and facility-level predictors of each domain. RESULTS: We examined six unique
domains of QOL: environment, personal attention, food, engagement, negative mood,
and positive mood. In multilevel models, resident-level characteristics were more
reliable correlates of QOL than facility characteristics. Among resident
characteristics, gender, age, marital status, activities of daily living, mood
disorders, cognitive limitations, and length of stay consistently predicted QOL
domains. Among facility characteristics, size, staff hours, quality of care, and
percent of residents on Medicaid predicted multiple QOL domains. IMPLICATIONS:
Examining separate domains rather than a single summary score makes associations
with predictors more accurate. Resident characteristics account for the majority
of variability in resident QOL. Helping residents maintain functional abilities,
and providing an engaging social environment may be particularly important in
improving QOL.
PMID- 24352534
TI - Polymeric plasticizer extends the lifetime of PVC-membrane ion-selective
electrodes.
AB - The nature of the plasticizer plays a pivotal role in the analytical performance
of polymer membrane ion sensors. Conventional plasticizers suffer leaching or
migration from the membrane and exudation, both of which could limit the lifetime
of sensors based on plasticized membranes. Herein, we describe the use of
polyester sebacate (PES), a model polymeric plasticizer, in the preparation of
poly (vinyl chloride) (PVC) membrane ion-selective electrodes (ISEs) using
valinomycin as ionophore. PVC membrane electrodes plasticized with polyester
sebacate demonstrated potentiometric response characteristics that compared
favorably to ones plasticized with the conventional and similarly structured
plasticizer bis(2-ethylhexyl) sebacate (DOS). Increasing the content of polyester
sebacate in the membrane enhanced the response and improved the selectivity of
valinomycin-based ISEs toward potassium over sodium. Various methods, including
electrochemical impedance spectroscopy, UV-vis spectroscopy, dark field optical
microscopy, and potentiometry were employed to study the effect of plasticizer on
the leaching of the membrane components and the lifetime of both DOS- and PES
plasticized membranes. PES-plasticized electrodes maintained Nernstian response
and high selectivity for more than four months, an improvement over DOS
plasticized membrane electrodes. This was attributed to enhanced retention of the
membrane components because of the high polymeric nature of the polyester
sebacate. These characteristics suggest that polyester sebacate is a good
candidate to replace the conventional plasticizers in preparing PVC membrane
electrodes with longer lifetime.
PMID- 24352533
TI - Micromonospora maoerensis sp. nov., isolated from a Chinese pine forest soil.
AB - A novel actinomycete, designated strain NEAU-MES19(T), was isolated from pine
forest soil in Heilongjiang province, China. A polyphasic study was carried out
to establish the taxonomic position of this strain. The organism was found to
have morphological and chemotaxonomic characteristics typical of the genus
Micromonospora. Phylogenetic analysis of the 16S rRNA gene sequence indicated
that strain NEAU-MES19(T) was most closely related to Micromonospora
matsumotoense IMSNU 22003(T). However, phylogenetic analysis based on the gyrB
gene sequence showed that the isolate was more closely related to Micromonospora
cremea CR30(T) than M. matsumotoense IMSNU 22003(T). The low level of DNA-DNA
relatedness allowed the isolate to be differentiated from M. matsumotoense IMSNU
22003(T) and M. cremea CR30(T). Moreover, strain NEAU-MES19(T) could also be
distinguished from its closest phylogenetic relatives by morphological,
physiological and biochemical characteristics. Therefore, it is proposed that
strain NEAU-MES19(T) represents a novel species of the genus Micromonospora, for
which the name Micromonospora maoerensis sp. nov. is proposed. The type strain is
NEAU-MES19(T) (=CGMCC 4.7091(T) = DSM 45884(T)).
PMID- 24352535
TI - Prolonged sedation of lorazepam due to absent UGT2B4/2B7 glucuronidation.
PMID- 24352537
TI - Mammalian toxicology and human exposures to the flame retardant 2,2',6,6'
tetrabromo-4,4'-isopropylidenediphenol (TBBPA): implications for risk assessment.
AB - The compound 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol
(tetrabromobisphenol A, TBBPA) is used as a reactive and additive flame
retardant. This review evaluates the mammalian toxicology of TBBPA and summarizes
recent human exposure and risk assessments. TBBPA has a low potential for
systemic or reproductive toxicity, and no-observed-adverse-effect-levels were
greater than 1,000 mg/kg body weight (bw)/day in a 90-day oral toxicity study, a
developmental toxicity study and a two-generation reproductive and developmental
toxicity study. Some interactions of TBBPA with hormone-mediated pathways were
noted in vitro; however, when studied in vivo, TBBPA did not produce adverse
effects that might be considered to be related to disturbances in the endocrine
system. Therefore, in accordance with internationally accepted definitions, TBBPA
should not be considered an "endocrine disruptor." Furthermore, TBBPA is rapidly
excreted in mammals and therefore does not have a potential for bioaccumulation.
Measured concentrations of TBBPA in house dust, human diet and human serum
samples are very low. Daily intakes of TBBPA in humans were estimated to not
exceed a few ng/kg bw/day. Due to the low exposures and the low potential for
toxicity, margins of exposures for TBBPA in the human population were between 6 *
10(4) (infants) to 6 * 10(7) (adults). Exposures of the general population are
also well below the derived-no-effect-levels derived for endpoints of potential
concern in REACH.
PMID- 24352536
TI - The broccoli-born isothiocyanate sulforaphane impairs nucleotide excision repair:
XPA as one potential target.
AB - The isothiocyanate sulforaphane (SFN), the major hydrolysis product of
glucosinolates present in broccoli, has frequently been proposed to exert
anticarcinogenic properties, mainly due to the induction of the nrf2/Keap1/ARE
signaling pathway. As potential underlying mechanism, a SFN-dependent zinc
release from Keap1, the negative regulator of nrf2, has been described. This
raises the question whether SFN is able to interfere with other zinc binding
structures as well, for example those essential for DNA repair. Within this
study, a SFN-induced deliberation of zinc from a synthesized peptide resembling
the zinc binding domain of the xeroderma pigmentosum A (XPA) protein was observed
starting at 50 MUM SFN. Since XPA is absolutely required for nucleotide excision
repair, the impact of SFN on the repair of (+)-anti-benzo[a]pyrene 7,8-diol-9,10
epoxide ((+)-anti-BPDE)-induced DNA adducts in HCT 116 cells was investigated.
While preincubation with SFN did not affect initial lesion levels, a dose
dependent repair inhibition of (+)-anti-BPDE-induced DNA damage during the first
12 h after lesion induction was observed, starting at 1 MUM SFN. In contrast, the
later phase of DNA repair was not impaired by SFN. In support of an inactivation
of XPA also in cells, SFN increased the (+)-anti-BPDE-induced cytotoxicity XPA
dependently in XP12RO cells. Comparison of p53-proficient and p53-deficient cells
revealed no difference in SFN-induced DNA repair inhibition, indicating that p53
is no cellular target of SFN. Since DNA repair processes are required to maintain
DNA integrity, the presented data suggest a potential impairment of genomic
stability by SFN.
PMID- 24352538
TI - Inhibition of tumour spheroid-induced prometastatic intravasation gates in the
lymph endothelial cell barrier by carbamazepine: drug testing in a 3D model.
AB - Metastatic breast cancer is linked to an undesired prognosis. One early and
crucial metastatic step is the interaction of cancer emboli with adjacent stroma
or endothelial cells, and understanding the mechanisms of this interaction
provides the basis to define new targets as well as drugs for therapy and disease
management. A three-dimensional (3D) co-culture model allowing the examination of
lymphogenic dissemination of breast cancer cells was recently developed which
facilitates not only the study of metastatic processes but also the testing of
therapeutic concepts. This 3D setting consists of MCF-7 breast cancer cell
spheroids (representing a ductal and hormone-dependent subtype) and of hTERT
immortalised lymph endothelial cell (LEC; derived from foreskin) monolayers.
Tumour spheroids repel the continuous LEC layer, thereby generating "circular
chemorepellent-induced defects" (CCIDs) that are reminiscent to the entry gates
through which tumour emboli intravasate lymphatics. We found that the ion channel
blocker carbamazepine (which is clinically used to treat epilepsy, schizophrenia
and other neurological disorders) inhibited CCID formation significantly. This
effect correlated with the inhibition of the activities of NF-kappaB, which
contributes to cell motility, and with the inactivation of the mobility proteins
MLC2, MYPT1 and FAK which are necessary for LEC migration. NF-kappaB activity and
cell movement are prerequisites of CCID formation. On the other hand, the
expression of the motility protein paxillin and of the NF-kappaB-dependent
adhesion mediator ICAM-1 was unchanged. Also the activity of ALOX12 was
unaffected. ALOX12 is the main enzyme synthesising 12(S)-HETE, which then
triggers CCID formation. The relevance of the inhibition of CYP1A1, which is also
involved in the generation of mid-chain HETEs such as 12(S)-HETE, by
carbamazepine remains to be established, because the constitutive level of 12(S)
HETE did not change upon carbamazepine treatment. Nevertheless, the effect of
carbamazepine on the inhibition of CCID formation as an early step of breast
cancer metastasis was significant and substantial (~30 %) and achieved at
concentrations that are found in the plasma of carbamazepine-treated adults (40
60 MUM). The fact that carbamazepine is a drug approved by the US Food and Drug
Administration facilitates a "from-bench-to-bedside" perspective. Therefore, the
here presented data should undergo scrutiny in vivo.
PMID- 24352539
TI - Effect of mycosynthesized silver nanoparticles from filtrate of Trichoderma
harzianum against larvae and pupa of dengue vector Aedes aegypti L.
AB - Mosquitoes transmit dreadful diseases, causing millions of deaths every year.
Therefore, screening for larvicidal and pupicidal activity of microbial extracts
attributes could lead to development of new and improved mosquito control methods
that are economical and safe for nontarget organisms and are ecofriendly.
Synthetic chemical insecticides occupy predominant position in control
strategies. These hazardous chemicals exert unwarranted toxicity and lethal
effects on nontarget organisms, develop physiological resistance in target, and
cause adverse environmental effect. For vector control, fungal-mediated natural
products have been a priority in this area at present. In the current study,
effective larvicidal and pupicidal effect of mycosynthesized silver nanoparticles
(Ag NPs) using an entomopathogenic fungi Trichoderma harzianum against
developmental stages of the dengue vector Aedes aegypti was investigated. An
attractive possibility of green nanotechnology is to use microorganisms in the
synthesis of nanosilver especially Ag NPs. The mycosynthesized Ag NPs were
characterized to find their unique properties through UV-visible
spectrophotometer, X-ray diffraction analysis, Fourier transform infrared, and
surface characteristics by scanning electron microscopy. To analyze the
bioefficacy, different test concentrations for extracellular filtrate (0.2, 0.4,
0.6, 0.8, and 1.0 %) and Ag NPs (0.05, 0.10, 0.15, 0.20, and 0.25 %) were
prepared to a final volume of 200 mL using deionized water; 20 larvae of each
instars (I-IV) and pupa were exposed to each test concentration separately which
included a set of control (distilled water) group with five replicates.
Characterization of the synthesized Ag NPs were about 10-20 nm without
aggregation. Susceptibility of larval instars to synthesized Ag NPs was higher
than the extracellular filtrate of T. harzianum alone after 24-h exposure, where
the highest mortality was recorded as 92 and 96 % for first and second instars
and 100 % for third, fourth instars, and pupa. Lethal concentration 50 values of
0.079, 0.084, 0.087, 0.068, and 0.026 % were recorded for I-IV instars and pupa,
respectively, when exposed to Ag NPs at 0.25 % concentration. Toxicity was
exhibited against first (1.076 %), second (0.912 %), third (0.770 %), fourth
(0.914 %) instars larvae, and pupa (0.387 %) with extracellular filtrate at a
concentration of 1 % that was three- to fourfold higher compared to Ag NPs; no
mortality was observed in the control. The present study is the first report on
effective larvicidal and pupicidal activity of Ag NPs synthesized from an
entomopathogenic fungi T. harzianum extracellular filtrate and could be an ideal
ecofriendly, single-step, and inexpensive approach for the control of A. aegypti.
PMID- 24352540
TI - Stability of 6:2 fluorotelomer sulfonate in advanced oxidation processes:
degradation kinetics and pathway.
AB - Perfluorooctane sulfonate (PFOS), a widely used mist suppressant in hard chrome
electroplating industry, has been listed in the Stockholm Convention for global
ban. 6:2 Fluorotelomer sulfonate (6:2 FTS) acid and salts have been adopted as
alternative products in the market, but no data about their abiotic degradation
has been reported. In the present study, the degradability of 6:2 FTS potassium
salt (6:2 FTS-K) was evaluated under various advanced oxidation processes,
including ultraviolet (UV) irradiation, UV with hydrogen peroxide (H2O2),
alkaline ozonation (O3, pH = 11), peroxone (O3/H2O2), and Fenton reagent
oxidation (Fe(2+)/H2O2). UV/H2O2 was found to be the most effective approach,
where the degradation of 6:2 FTS-K followed the pseudo-first-order kinetics. The
intermediates were mainly shorter chain perfluoroalkyl carboxylic acid (C7 to
C2), while sulfate (SO4 (2-)) and fluoride (F(-)) were found to be the final
products. The high yields of SO4 (2-) and F(-) indicate that 6:2 FTS-K can be
nearly completely desulfonated and defluorinated under UV/H2O2 condition. The
degradation should firstly begin with the substitution of hydrogen atom by
hydroxyl radicals, followed by desulfonation, carboxylation, and sequential
"flake off" of CF2 unit. Compared with PFOS which is inert in most advanced
oxidation processes, 6:2 FTS-K is more degradable as the alternative.
PMID- 24352541
TI - Sensitivity of hypogean and epigean freshwater copepods to agricultural
pollutants.
AB - Widespread pollution from agriculture is one of the major causes of the poor
freshwater quality currently observed across Europe. Several studies have
addressed the direct impact of agricultural pollutants on freshwater biota by
means of laboratory bioassays; however, as far as copepod crustaceans are
concerned, the ecotoxicological research is scarce for freshwater species and
almost nonexistent for the hypogean ones. In this study, we conducted a
comparative analysis of the available literature data on the sensitivity of
freshwater copepods to agricultural pollutants. We also assessed the acute and
chronic sensitivity of a hypogean and an epigean species, both belonging to the
Crustacea Copepoda Cyclopoida Cyclopidae, to two N-fertilizers (urea and ammonium
nitrate) and two herbicides (ARIANE(TM) II from Dow AgroSciences LLC, and
Imazamox), widely used for cereal agriculture in Europe. According to the
literature review, freshwater copepods are sensitive to a range of pesticides and
N-fertilizers. Ecotoxicological studies on hypogean species of copepods account
only one study. There are no standardized protocols available for acute and
chronic toxicity tests for freshwater copepods, making comparisons about
sensitivity difficult. From our experiments, ionized ammonia proved to be more
toxic than the herbicide Imazamox, in both short and chronic bioassays. Urea was
the less toxic chemical for both species. The hypogean species was more sensitive
than the epigean one to all chemicals. For both species and for all tested
chemicals, acute lethality and chronic lethality were induced at concentrations
higher than the law limits of good water body quality in Europe, except for
ionized ammonia, which provoked the chronic lethality of the hypogean species at
a lower concentration. The hazardous concentration (HC) of un-ionized ammonia for
5 % of freshwater copepods, obtained by a species sensitivity distribution, was
92 MUg l(-1), significantly lower than the HC computed for traditional test
species from freshwater environments.
PMID- 24352542
TI - Effect of temperature and particle size on the thermal desorption of PCBs from
contaminated soil.
AB - Thermal desorption is widely used for remediation of soil contaminated with
volatiles, such as solvents and distillates. In this study, a soil contaminated
with semivolatile polychlorinated biphenyls (PCBs) was sampled at an interim
storage point for waste PCB transformers and heated to temperatures from 300 to
600 degrees C in a flow of nitrogen to investigate the effect of temperature and
particle size on thermal desorption. Two size fractions were tested: coarse soil
of 420-841 MUm and fine soil with particles <250 MUm. A PCB removal efficiency of
98.0 % was attained after 1 h of thermal treatment at 600 degrees C. The
residual amount of PCBs in this soil decreased with rising thermal treatment
temperature while the amount transferred to the gas phase increased up to 550
degrees C; at 600 degrees C, destruction of PCBs became more obvious. At low
temperature, the thermally treated soil still had a similar PCB homologue
distribution as raw soil, indicating thermal desorption as a main mechanism in
removal. Dechlorination and decomposition increasingly occurred at high
temperature, since shifts in average chlorination level were observed, from 3.34
in the raw soil to 2.75 in soil treated at 600 degrees C. Fine soil particles
showed higher removal efficiency and destruction efficiency than coarse
particles, suggesting that desorption from coarse particles is influenced by mass
transfer.
PMID- 24352543
TI - Influence of spontaneous vegetation in stormwater infiltration system clogging.
AB - The paper presents the role of spontaneous vegetation on the hydraulic
performance of an infiltration basin. The objective of the research was more
particularly to study this role of different types of spontaneous vegetation
found in situ in an infiltration basin near Lyon. The saturated hydraulic
conductivity of three areas covered by Phalaris arundinacea, Polygonum mite,
Rumex crispus and similar non-vegetated zones was compared. Eight field campaigns
were carried out from July 2010 to May 2011 in order to compare the performance
of each type of vegetation and its evolution over time. The results suggest a
positive impact of vegetation on hydraulic performance in particular in summer
during the growth of the plants. The hydraulic conductivity in this period was
twice to four times higher than in bare areas or in vegetated zones during the
plant rest periods. Some species were also found more appropriate to limit
clogging (Phalaris arundinacea) likely due to its specific structure and growth
process.
PMID- 24352544
TI - The effects of cadmium or zinc multigenerational exposure on metal tolerance of
Spodoptera exigua (Lepidoptera: Noctuidae).
AB - The effects of ten generational zinc or cadmium pre-exposure on metal tolerance
among beet armyworm Spodoptera exigua individuals were compared. These effects
were assessed in animals from the 11th generation, reared on a diet either
uncontaminated or contaminated with metal (cadmium or zinc). The survival rate of
larvae and the degree of metal accumulation (in larvae, pupae and moths; among
larval organs: gut and fat body) were analysed. Catalase, superoxide dismutase
and glutathione transferase activity in larval organs of individuals subjected to
different metal treatments were also measured. Animals transferred from control
rearing to metals (cadmium or zinc) in the 11th generation, as well as those from
multigenerational zinc treatment, but not from multigenerational cadmium
treatment, had a significantly lower survival rate than control animals. Insects
from the groups with the high metal treatment had high bioaccumulation factors
(above 3.7 and 2.3 following cadmium and zinc, respectively). Cadmium (but not
zinc) pre-exposure had a significant effect on metal accumulation in larvae.
Multigenerational metal pre-exposure seemed to have mainly a negative effect on
glutathione transferase activity in the gut of larvae from the 11th generation,
in the case of the individuals exposed to metal other than that used in pre
exposure treatment or kept in control conditions. However, in the case of zinc
pre-exposure, such effect was only apparent when zinc was replaced by cadmium.
The long-term effect of cadmium on catalase activity in larvae was found.
PMID- 24352545
TI - Combined bioremediation of atrazine-contaminated soil by Pennisetum and
Arthrobacter sp. strain DNS10.
AB - Strain DNS10 was isolated from the black soil collected from the northeast of
China which had been cultivated with atrazine as the sole nitrogen source.
Pennisetum is a common plant in Heilongjiang Province of China. The main
objective of this paper was to evaluate the efficiency of plant-microbe joint
interactions (Arthrobacter sp. DNS10 + Pennisetum) in atrazine degradation
compared with single-strain and single-plant effects. Plant-microbe joint
interactions degraded 98.10 % of the atrazine, while single strain and single
plant only degraded 87.38 and 66.71 % after a 30-day experimental period,
respectively. The results indicated that plant-microbe joint interactions had a
better degradation effect. Meanwhile, we found that plant-microbe joint
interactions showed a higher microbial diversity. The results of microbial
diversity illustrated that the positive effects of cropping could improve soil
microbial growth and activity. In addition, we planted atrazine-sensitive plants
(soybean) in the soil after repair. The results showed that soybean growth in
soil previously treated with the plant-microbe joint interactions treatment was
better compared with other treatments after 20 days of growth. This was further
proved that the soil is more conducive for crop cultivation. Hence, plant-microbe
joint interactions are considered to be a potential tool in the remediation of
atrazine-contaminated soil.
PMID- 24352546
TI - Risk assessment of heavy metal toxicity of soil irrigated with treated wastewater
using heat shock proteins stress responses: case of El Hajeb, Sfax, Tunisia.
AB - Heavy metal contamination of soil resulting from treated wastewater irrigation
can cause serious concerns resulting from consuming contaminated crops.
Therefore, it is crucial to assess hazard related to wastewater reuse. In the
present investigation, we suggest the use of biomarker approach as a new tool for
risk assessment of wastewater reuse in irrigation as an improvement to the
conventional detection of physicochemical accumulation in irrigated sites. A
field study was conducted at two major sites irrigated with treated wastewater
and comparisons were made with a control site. Different soil depths were
considered to investigate the extent of heavy metal leaching, the estrogenic
activity, and the biomarker response. Results have shown that a longer irrigation
period (20 years) caused a slight decrease in soil metal levels when compared to
the soil irrigated for 12 years. The highest levels of Cr, Co, Ni, Pb, and Zn
were detected at 20 and 40 cm horizons in plots irrigated with wastewater for 12
years. The latter finding could be attributed to chemical leaching to deeper
plots for longer irrigation period. Furthermore, the treated wastewater sample
showed a high estrogenic activity while none of the soil samples could induce any
estrogenic activity. Regarding the stress response, it was observed that the
highest stress shown by the HSP47 promoter transfected cells was induced by a
longer irrigation period. Finally, the treated wastewater and the irrigated soils
exhibited an overexpression of HSP60 in comparison with reference soil following
1 h exposure. In conclusion, in vitro techniques can be efficiently used to
assess potential hazard related to wastewater reuse.
PMID- 24352547
TI - Ammonia concentrations and modeling of inorganic particulate matter in the
vicinity of an egg production facility in Southeastern USA.
AB - Ammonia (NH3) is an important base gas and can react with acidic species to form
atmospheric aerosols. Due to the rapid growth of poultry and swine production in
the North Carolina Coastal Plain, atmospheric NH3 concentrations across the
region have subsequently increased. Ammonia concentrations and inorganic
particulate matter (PM) at four ambient stations in the vicinity of an egg
production facility were measured for 1 year using PM2.5 speciation samplers with
honeycomb denuders and ion chromatography (IC). Meanwhile, concentrations of NH3
and inorganic PM in one of the egg production houses were also simultaneously
measured using a gas analyzer for NH3 and the filter pack plus IC method for
inorganic PM. An equilibrium model-ISORROPIA II was applied to predict the
behavior of inorganic aerosols in response to precursor gas concentrations and
environmental parameters. Average ambient NH3 concentrations varied from 10.0 to
27.0 MUg/m(3), and they were negatively correlated with the distances from the
ambient location to the nearest egg production house exhausts. Ambient NH3
concentrations were higher in warm seasons than in cold seasons. Measured NH3
concentrations agreed well with ISORROPIA II model predictions at all sampling
stations. For the ambient stations, there was a good agreement in particle phase
NH4 (+) between the model simulation and observations. For the in-house station,
the model simulation was applied to correct the overestimation of particle phase
NH4 (+) due to gas phase NH3 breaking through the denuders. Changes in SO4 (2-),
NO3 (-), and Cl(-) yield proportional changes in inorganic PM mass. Due to the
abundance of NH3 gas in the vicinity area of the monitored farm, changes in NH3
concentrations had a small effect on inorganic PM mass. Aerosol equilibrium
modeling may be used to assess the influence of precursor gas concentrations on
inorganic PM formation when the measurements for some species are unavailable.
PMID- 24352548
TI - Biochar- and phosphate-induced immobilization of heavy metals in contaminated
soil and water: implication on simultaneous remediation of contaminated soil and
groundwater.
AB - Long-term wastewater irrigation or solid waste disposal has resulted in the heavy
metal contamination in both soil and groundwater. It is often separately
implemented for remediation of contaminated soil or groundwater at a specific
site. The main objective of this study was to demonstrate the hypothesis of
simultaneous remediation of both heavy metal contaminated soil and groundwater by
integrating the chemical immobilization and pump-and-treat methods. To accomplish
the objective, three experiments were conducted, i.e., an incubation experiment
was first conducted to determine how dairy-manure-derived biochar and phosphate
rock tailing induced immobilization of Cd in the Cd-contaminated soils; second, a
batch sorption experiment was carried out to determine whether the pre-amended
contaminated soil still had the ability to retain Pb, Zn and Cd from aqueous
solution. BCR sequential extraction as well as XRD and SEM analysis were
conducted to explore the possible retention mechanism; and last, a laboratory
scale model test was undertaken by leaching the Pb, Zn, and Cd contaminated
groundwater through the pre-amended contaminated soils to demonstrate how the
heavy metals in both contaminated soil and groundwater were simultaneously
retained and immobilized. The incubation experiment showed that the phosphate
biochar were effective in immobilizing soil Cd with Cd concentration in TCLP
(toxicity characteristics leaching procedure) extract reduced by 19.6 % and 13.7
%, respectively. The batch sorption experiment revealed that the pre-amended soil
still had ability to retain Pb, Zn, and Cd from aqueous solution. The phosphate
induced metal retention was mainly due to the metal-phosphate precipitation,
while both sorption and precipitation were responsible for the metal
stabilization in the biochar amendment. The laboratory-scale test demonstrated
that the soil amended with phosphate removed groundwater Pb, Zn, and Cd by 96.4
%, 44.6 %, and 49.2 %, respectively, and the soil amended with biochar removed
groundwater Pb, Zn, and Cd by 97.4 %, 53.4 %, and 54.5 %, respectively.
Meanwhile, the metals from both groundwater and soil itself were immobilized with
the amendments, with the leachability of the three metals in the CaCl2 and TCLP
extracts being reduced by up to 98.1 % and 62.7 %, respectively. Our results
indicate that the integrated chemical immobilization and pump-and-treat method
developed in this study provides a novel way for simultaneous remediation of both
metal-contaminated soil and groundwater.
PMID- 24352550
TI - Assessing the enrichment of heavy metals in surface soil and plant (Digitaria
eriantha) around coal-fired power plants in South Africa.
AB - Nine metals (Fe, Cu, Mn, Ni, Cd, Pb, Hg, Cr, and Zn) were determined in soil and
Digitaria eriantha plants within the vicinity of three coal power plants (Matla,
Lethabo, and Rooiwal), using ICP-OES and GFAAS. The total metal concentration in
soil ranged from 0.05 +/- 0.02 to 1836 +/- 70 MUg g(-1), 0.08 +/- 0.05 to 1744 +/
29 MUg g(-1), and 0.07 +/- 0.04 to 1735 +/- 91 MUg g(-1) in Matla, Lethabo, and
Rooiwal, respectively. Total metal concentration in the plant (D. eriantha)
ranged from 0.005 +/- 0.003 to 535 +/- 43 MUg g(-1) in Matla, 0.002 +/- 0.001 to
400 +/- 269 MUg g(-1) in Lethabo, and 0.002 +/- 0.001 to 4277 +/- 201 MUg g(-1)
in Rooiwal. Accumulation factors (A) of less than 1 (i.e., 0.003 to 0.37) at all
power plants indicate a low transfer of metal from soil to plant (excluder).
Enrichment factor values obtained (2.4-5.0) indicate that the soils are
moderately enriched with the exception of Pb that had significant enrichment of
20. Geo-accumulation index (I-geo) values of metals indicate that the soils are
moderately polluted (0.005-0.65), except for Pb that showed moderate to strong
pollution (1.74-2.53).
PMID- 24352549
TI - Occurrence and suitability of pharmaceuticals and personal care products as
molecular markers for raw wastewater contamination in surface water and
groundwater.
AB - This study aimed to provide the first and comprehensive data on the occurrence of
17 target pharmaceuticals and personal care products (PPCPs) in urban water
environment in Singapore. Meanwhile, this study also verified the suitability of
these PPCPs as specific markers of raw wastewater contamination in receiving
water bodies in highly urbanized areas where both surface water and groundwater
are not impacted by the discharge of treated wastewater effluents. Analytical
results of wastewater showed that among 17 target PPCPs examined, only 5 PPCPs
were detected in 100 % of raw wastewater samples, including acetaminophen (ACT),
carbamazepine (CBZ), caffeine (CF), diethyltoluamide (DEET), and salicylic acid
(SA). Similarly, these PPCPs were found in most surface water and groundwater.
Interestingly, the three PPCPs (ACT, CBZ, and SA) were only detected in surface
water and groundwater in the sampling sites close to relatively older sewer
systems, while they were absent in background samples that were collected from
the catchment with no known wastewater sources. This suggests that ACT, CBZ, and
SA can be used as specific molecular markers of raw wastewater in surface water
and groundwater. This study also confirmed that CF and DEET were not really
associated with wastewater sources, thus cannot serve well as specific molecular
markers of wastewater contamination in receiving water bodies. To the best
knowledge of the authors, the use of ACT and SA as specific molecular markers of
raw wastewater contamination in urban surface waters and groundwater was first
reported. Further studies on the use of ACT, CBZ, and SA along with other
chemical/microbial markers are recommended to identify and differentiate
contamination sources of surface waters/groundwater.
PMID- 24352551
TI - Effects of cadmium on the photosynthetic activity in mature and young leaves of
soybean plants.
AB - Cadmium (Cd) is a widely spread pollutant and can be easily taken up by crop from
soil, resulting in a serious health issue for humans. The objective of this study
was to comparatively investigate the photosynthetic activity, chlorophyll a
fluorescence, chlorophyll contents, and spectral reflectance in mature and young
leaves of soybean plants after being treated with different concentrations of Cd
for 10 days. The photosynthetic rate, chlorophyll contents, actual photochemical
efficiency of PSII, and photochemical quenching in the young leaves decreased
more significantly with increasing concentrations of Cd in the nutrient solution,
compared with those in the mature leaves, though the young leaves had less Cd
concentrations. Thus, there was more excessive excited energy produced in the
young leaves than that in the mature leaves. In the young leaves, due to more
excessive excited energy, more reactive oxygen species may be generated, which
further damaged the photosynthetic apparatus. It was supported by the fact that
the decrease of reflectance in near-infrared wavelengths of the young leaves was
more noticeable than that of the mature leaves. In addition, the chlorophyll a
fluorescence transients of the young leaves was significantly different from that
in the mature leaves, indicating that the electron transport of young leaves were
inhibited much more severely than that of the mature leaves. These observations
imply that the responses of photosynthetic activity of soybean leaves to Cd
stress depend on their growth stage, and the Cd-induced inhibition of
photosynthetic activity might be attributed to the decrease in chlorophyll
contents and the decrease in mesophyll CO2 assimilation ability cause by the Cd,
which further decreased the consumption of ATP and NADPH, leading to accumulation
of NADPH on the acceptor sides of the PSI, and then feedback inhibited electron
transport in chloroplasts.
PMID- 24352552
TI - Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and
perfluorinated alkylated substances (PFASs) in traditional seafood items from
western Greenland.
AB - In this study, contamination levels were determined for polychlorinated biphenyls
(PCBs), polybrominated diphenyl ethers (PBDEs) and perfluorinated alkylated
substances (PFASs) in traditional Greenland seafood items, such as raw and smoked
fish fillet (salmon and halibut), whale and seal meat and narwhal mattak (skin
and blubber). The daily intake of PCBs, PBDEs and PFASs through traditional
seafood items in Greenland was assessed. Based on the presented levels of
contaminants, in combination with earlier food intake studies, suggests that the
daily exposure was below the tolerable daily intake threshold for all compounds.
BDE-47 was the only PBDE-congener detected in all food items, except in smoked
halibut. The levels of BDE-47 varied from < LOD in smoked halibut up to 18 ng/g
lw in narwhal mattak and 21 ng/g lw in whale beef. ?PCB were lowest in smoked
halibut (37 ng/g lw) and highest in narwhal mattak with 1,146 ng/g lw.
Perfluorooctane sulfonate (PFOS) was the most common of the PFASs. However,
SigmaPFASs were below detection limits in most fish fillet samples, and varied
from 2.9 ng/g ww in whale beef to 13.5 ng/g ww in seal beef. The present study
shows that the exclusion from the diet of local food items such as intestines and
blubber have a strong positive effect for the reduction of POPs levels in food,
without a reducing the health benefits of traditional food intake considerably.
PMID- 24352553
TI - Improving the quality of cancer care in America through health information
technology.
AB - A recent report from the Institute of Medicine titled Delivering High-Quality
Cancer Care: Charting a New Course for a System in Crisis, identifies improvement
in information technology (IT) as essential to improving the quality of cancer
care in America. The report calls for implementation of a learning healthcare IT
system: a system that supports patient-clinician interactions by providing
patients and clinicians with the information and tools necessary to make well
informed medical decisions and to support quality measurement and improvement.
While some elements needed for a learning healthcare system are already in place
for cancer, they are incompletely implemented, have functional deficiencies, and
are not integrated in a way that creates a true learning healthcare system. To
achieve the goal of a learning cancer care delivery system, clinicians,
professional organizations, government, and the IT industry will have to partner,
develop, and incentivize participation.
PMID- 24352555
TI - Tetrahedral tetrazolate frameworks for high CO2 and H2 uptake.
AB - Three tetrahedral tetrazolate frameworks with two different 4-connected
topologies including lonsdaleite (lon, for 1) and diamond (dia, for 2 and 3) have
been synthesized, and the lon-type framework with high CO2 and H2 uptake capacity
can irreversibly transform to the dia-type framework via solvent-exchange.
PMID- 24352554
TI - Structure of a photosynthetic reaction centre determined by serial femtosecond
crystallography.
AB - Serial femtosecond crystallography is an X-ray free-electron-laser-based method
with considerable potential to have an impact on challenging problems in
structural biology. Here we present X-ray diffraction data recorded from
microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8
A resolution and determine its serial femtosecond crystallography structure to
3.5 A resolution. Although every microcrystal is exposed to a dose of 33 MGy, no
signs of X-ray-induced radiation damage are visible in this integral membrane
protein structure.
PMID- 24352519
TI - Heart disease and stroke statistics--2014 update: a report from the American
Heart Association.
PMID- 24352556
TI - GATA4 autoregulates its own expression in mouse gonadal cells via its distal 1b
promoter.
AB - Transcription factor GATA4 is required for the development and function of the
mammalian gonads. We first reported that the GATA4 gene in both human and rodents
is expressed as two major alternative transcripts that differ solely in their
first untranslated exon (exon 1a vs. exon 1b). We had also showed by quantitative
PCR that in mouse tissues, both Gata4 exon 1a- and 1b-containing transcripts are
present in all sites that are normally positive for GATA4 protein. In adult
tissues, exon 1a-containing transcripts generally predominate. A notable
exception, however, is the testis where the Gata4 exon 1a and 1b transcripts
exhibit a similar level of expression. We now confirm by in situ hybridization
analysis that each transcript is also strongly expressed during gonad
differentiation in both sexes in the rat. To gain further insights into how Gata4
gene expression is controlled, we characterized the mouse Gata4 promoter sequence
located upstream of exon 1b. In vitro studies revealed that the Gata4 1b promoter
is less active than the 1a promoter in several gonadal cell lines tested. Whereas
we have previously shown that endogenous Gata4 transcription driven by the 1a
promoter is dependent on a proximally located Ebox motif, we now show using
complementary in vitro and in vivo approaches that Gata4 promoter 1b-directed
expression is regulated by GATA4 itself. Thus, Gata4 transcription in the gonads
and other tissues is ensured by distinct promoters that are regulated
differentially and independently.
PMID- 24352557
TI - P2X1 receptors localized in lipid rafts mediate ATP motor responses in the human
vas deferens longitudinal muscles.
AB - To assess the role of the P2X1 receptors (P2X1R) in the longitudinal and circular
layers of the human vas deferens, ex vivo-isolated strips or rings were prepared
from tissue biopsies to record isometric contractions. To ascertain its membrane
distribution, tissue extracts were analyzed by immunoblotting following sucrose
gradient ultracentrifugation. ATP, alpha,beta-methylene ATP, or electrical field
stimulation elicited robust contractions of the longitudinal layer but not of the
circular layer which demonstrated inconsistent responses. Alpha,beta-methylene
ATP generated stronger and more robust contractions than ATP. In parallel,
prostatic segments of the rat vas deferens were examined. The motor responses in
both species were not sustained but decayed within the first minute, showing
desensitization to additional applications. Cross-desensitization was established
between alpha,beta-methylene ATP or ATP-evoked contractions and electrical field
stimulation-induced contractions. Full recovery of the desensitized motor
responses required more than 30 min and showed a similar pattern in human and rat
tissues. Immunoblot analysis of the human vas deferens extracts revealed a P2X1R
oligomer of approximately 200 kDa under nonreducing conditions, whereas
dithiothreitol-treated extracts showed a single band of approximately 70 kDa. The
P2X1R was identified in ultracentrifugation fractions containing 15%-29% sucrose;
the receptor localized in the same fractions as flotillin-1, indicating that it
regionalized into smooth muscle lipid rafts. In conclusion, ATP plays a key role
in human vas deferens contractile responses of the longitudinal smooth muscle
layer, an effect mediated through P2X1Rs.
PMID- 24352558
TI - Peri-implantation hormonal milieu: elucidating mechanisms of abnormal
placentation and fetal growth.
AB - Assisted reproductive technologies (ART) have been associated with several
adverse perinatal outcomes involving placentation and fetal growth. It is
critical to examine each intervention individually in order to assess its
relationship to the described adverse perinatal outcomes. One intervention
ubiquitously used in ART is superovulation with gonadotropins. Superovulation
results in significant changes in the hormonal milieu, which persist during the
peri-implantation and early placentation periods. Epidemiologic evidence suggests
that the treatment-induced peri-implantation maternal environment plays a
critical role in perinatal outcomes. In this study, using the mouse model, we
have isolated the exposure to the peri-implantation period, and we examine the
effect of superovulation on placentation and fetal growth. We report that the
nonphysiologic peri-implantation maternal hormonal environment resulting from
gonadotropin stimulation appears to have a direct effect on fetal growth,
trophoblast differentiation, and gene expression. This appears to be mediated, at
least in part, through trophoblast expansion and invasion. Although the specific
molecular and cellular mechanism(s) leading to these observations remain to be
elucidated, identifying this modifiable risk factor will not only allow us to
improve perinatal outcomes with ART, but help us understand the pathophysiology
contributing to these outcomes.
PMID- 24352560
TI - Correlation of parents' religious behavior with family's emotional relations and
students' self-actualization.
AB - The main goal of this research is to study the relationship between parents'
religious behavior, emotional relations inside family, and self-actualization of
male and female high school students of district 2 in Kerman city. Research
method is descriptive and of correlative type. Questionnaires of parent's
religious behavior, emotional relations inside family, and students' self
actualization were used in the research. After collecting questionnaires, data
were analyzed by SPSS, MINITAB, and EXCEL software. The sample volume in the
research has been 309 students and their parents, and the sampling method was in
the form of classification and then in the form of cluster in two stages. 1.29 %
of students had a low self-actualization, 17.15 % had average, and 81.55 % of
them had high self-actualization. Also the results showed that 9.4 % of emotional
relations in families were undesirable, 55.3 % were relatively desirable, and
35.3 % were desirable. Moreover, 2.27 % of parents' religious behavior was
inappropriate, 29.13 % was relatively appropriate, and 68.61 % was appropriate.
The main results of the research are as follows: (1) There is a significant
positive correlation between parents' religious behavior and emotional relations
inside students' family. (2) There is not any significant correlational between
parents' religious behavior and students' self-actualization. (3) There is a
significant positive correlation between emotional relations inside family and
students' self-actualization.
PMID- 24352559
TI - Maternal and fetoplacental hypoxia do not alter circulating angiogenic growth
effectors during human pregnancy.
AB - One causal model of preeclampsia (PE) postulates that placental hypoxia alters
the production of angiogenic growth effectors (AGEs), causing an imbalance
leading to maternal endothelial cell dysfunction. We tested this model using the
natural experiment of high-altitude (HA) residence. We hypothesized that in HA
pregnancies 1) circulating soluble fms-like tyrosine kinase 1 (sFlt-1) is
increased and placental growth factor (PlGF) decreased, and 2) AGE concentrations
correlate with measures of hypoxia. A cross-sectional study of healthy
pregnancies at low altitude (LA) (400 m) versus HA (3600 m) compared normal (n =
80 at HA, n = 90 at LA) and PE pregnancies (n = 20 PE at HA, n = 19 PE at LA).
Blood was collected using standard serum separation and, in parallel, by a method
designed to inhibit platelet activation. AGEs were measured by enzyme-linked
immunosorbent assays. AGEs did not differ between altitudes in normal or PE
pregnancies. AGE concentrations were unrelated to measures of maternal or fetal
hypoxia. PlGF was lower and sFlt-1 higher in PE, but overlapped considerably with
the range observed in normal samples. PlGF correlated with placental mass in both
normal and PE pregnancies. The contribution of peripheral cells to the values
measured for AGEs was similar at LA and HA, but was greater in PE than in
normotensive women. Hypoxia, across a wide physiological range in pregnancy, does
not alter levels of circulating AGEs in otherwise normal pregnancies. Peripheral
cell release of AGEs with the hemostasis characteristic of standard blood
collection is highly variable and contributes to a doubling of the amount of sFlt
1 measured in PE as compared to normal pregnancies.
PMID- 24352561
TI - Greater thickness of the aortic wall on postmortem computed tomography compared
with antemortem computed tomography: the first longitudinal study.
AB - OBJECTIVES: To evaluate postmortem changes of the aorta on postmortem computed
tomography (CT) in comparison with those on antemortem CT obtained in the same
patients. MATERIALS AND METHODS: We studied 57 consecutive patients who had
undergone antemortem CT, postmortem CT, and pathological autopsy in our tertiary
care hospital between April 2009 and December 2010. Postmortem CT was performed
within 20 h after death, followed by pathological autopsy. Pathological autopsy
confirmed the absence of cardiovascular disease such as aortic aneurysm, aortic
dissection, or Marfan syndrome in all patients. Aortic wall thickness and aortic
cross-sectional areas were measured on both antemortem CT and postmortem CT.
Difference in aortic wall thickness between antemortem CT with and without
contrast medium, and between antemortem CT and postmortem CT, and in cross
sectional area of the aortic wall between antemortem CT and postmortem CT was
evaluated statistically. RESULTS: No significant difference in aortic wall
thickness was observed on antemortem CT in comparison of contrasted and non
contrasted images. The aortic wall was significantly thicker on postmortem CT
than on antemortem CT (p < 0.0001). No significant difference in cross-sectional
area of the aortic wall was observed between antemortem CT and postmortem CT
measurements. CONCLUSION: This is the first longitudinal study to confirm greater
thickness of the aortic wall on postmortem images compared with antemortem images
in the same patients and to show no change in cross-sectional area of the aortic
wall between before and after death.
PMID- 24352562
TI - Recovery of sparse translation-invariant signals with continuous basis pursuit.
AB - We consider the problem of decomposing a signal into a linear combination of
features, each a continuously translated version of one of a small set of
elementary features. Although these constituents are drawn from a continuous
family, most current signal decomposition methods rely on a finite dictionary of
discrete examples selected from this family (e.g., shifted copies of a set of
basic waveforms), and apply sparse optimization methods to select and solve for
the relevant coefficients. Here, we generate a dictionary that includes auxiliary
interpolation functions that approximate translates of features via adjustment of
their coefficients. We formulate a constrained convex optimization problem, in
which the full set of dictionary coefficients represents a linear approximation
of the signal, the auxiliary coefficients are constrained so as to only represent
translated features, and sparsity is imposed on the primary coefficients using an
L1 penalty. The basis pursuit denoising (BP) method may be seen as a special
case, in which the auxiliary interpolation functions are omitted, and we thus
refer to our methodology as continuous basis pursuit (CBP). We develop two
implementations of CBP for a one-dimensional translation-invariant source, one
using a first-order Taylor approximation, and another using a form of
trigonometric spline. We examine the tradeoff between sparsity and signal
reconstruction accuracy in these methods, demonstrating empirically that
trigonometric CBP substantially outperforms Taylor CBP, which in turn offers
substantial gains over ordinary BP. In addition, the CBP bases can generally
achieve equally good or better approximations with much coarser sampling than BP,
leading to a reduction in dictionary dimensionality.
PMID- 24352563
TI - Ion concentration polarization-based continuous separation device using
electrical repulsion in the depletion region.
AB - We proposed a novel separation method, which is the first report using ion
concentration polarization (ICP) to separate particles continuously. We analyzed
the electrical forces that cause the repulsion of particles in the depletion
region formed by ICP. Using the electrical repulsion, micro- and nano-sized
particles were separated based on their electrophoretic mobilities. Because the
separation of particles was performed using a strong electric field in the
depletion region without the use of internal electrodes, it offers the advantages
of simple, low-cost device fabrication and bubble-free operation compared with
conventional continuous electrophoretic separation methods, such as miniaturizing
free-flow electrophoresis (MU-FFE). This separation device is expected to be a
useful tool for separating various biochemical samples, including cells,
proteins, DNAs and even ions.
PMID- 24352564
TI - Data from ACS NSQIP on CRS-HIPEC: can they cool off the controversies?
PMID- 24352565
TI - Identification of CalDAG-GEFI as an intracellular target for the vicinal dithiol
binding agent phenylarsine oxide in human platelets.
AB - CalDAG-GEFI, a guanine nucleotide exchange factor activating Rap1, is known to
play a key role in Ca2+-dependent glycoprotein (GP)IIb/IIIa activation and
platelet aggregation. Although inhibition of CalDAG-GEFI could be a potential
strategy for antiplatelet therapy, no inhibitor of this protein has been
identified. In the present study, phenylarsine oxide (PAO), a vicinal dithiol
blocker, potently prevented Rap1 activation in thrombin-stimulated human
platelets without significantly inhibiting intracellular Ca2+ mobilisation and
protein kinase C activation. PAO also prevented the Ca2+ ionophore-induced Rap1
activation and platelet aggregation, which are dependent on CalDAG-GEFI. In the
biotin-streptavidin pull-down assay, CalDAG-GEFI was efficiently pull-downed by
streptavidin beads from the lysates of biotin-conjugated PAO-treated platelets,
suggesting that PAO binds to intracellular CalDAG-GEFI with high affinity. The
above effects of PAO were reversed by a vicinal dithiol compound 2,3
dimercaptopropanol. In addition, CalDAG-GEFI formed disulfide-linked oligomers in
platelets treated with the thiol-oxidant diamide, indicating that CalDAG-GEFI
contains redox-sensitive thiols. In a purified recombinant protein system, PAO
directly inhibited CalDAG-GEFI-stimulated GTP binding to Rap1. Using CalDAG-GEFI
and Rap1-overexpressed human embryonic kidney 293T cells, we further confirmed
that PAO abolished Ca2+-mediated Rap1 activation. Taken together, these results
have demonstrated that CalDAG-GEFI is one of the targets of action of PAO, and
propose an important role of vicinal cysteines for the functions of CalDAG-GEFI.
PMID- 24352566
TI - A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions.
AB - p-21 activated 6 (PAK6), first identified as interacting with the androgen
receptor (AR), is over-expressed in multiple cancer tissues and has been linked
to the progression of prostate cancer, however little is known about PAK6
function in the absence of AR signaling. We report here that PAK6 is specifically
required for carcinoma cell-cell dissociation downstream of hepatocyte growth
factor (HGF) for both DU145 prostate cancer and HT29 colon cancer cells.
Moreover, PAK6 overexpression can drive cells to escape from adhesive colonies in
the absence of stimulation. We have localized PAK6 to cell-cell junctions and
have detected a direct interaction between the kinase domain of PAK6 and the
junctional protein IQGAP1. Co-expression of IQGAP1 and PAK6 increases cell colony
escape and leads to elevated PAK6 activation. Further studies have identified a
PAK6/E-cadherin/IQGAP1 complex downstream of HGF. Moreover, we find that beta
catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6
substrate. We propose a unique role for PAK6, independent of AR signaling, where
PAK6 drives junction disassembly during HGF-driven cell-cell dissociation via an
IQGAP1/E-cadherin complex that leads to the phosphorylation of beta-catenin and
the disruption of cell-cell adhesions.
PMID- 24352567
TI - Aging of the mammalian gastrointestinal tract: a complex organ system.
AB - Gastrointestinal disorders are a major cause of morbidity in the elderly
population. The gastrointestinal tract is the most complex organ system; its
diverse cells perform a range of functions essential to life, not only secretion,
digestion, absorption and excretion, but also, very importantly, defence. The
gastrointestinal tract acts not only as a barrier to harmful materials and
pathogens but also contains the vast number of beneficial bacterial populations
that make up the microbiota. Communication between the cells of the
gastrointestinal tract and the central nervous and endocrine systems modifies
behaviour; the organisms of the microbiota also contribute to this brain-gut
enteric microbiota axis. Age-related physiological changes in the gut are not
only common, but also variable, and likely to be influenced by external factors
as well as intrinsic aging of the cells involved. The cellular and molecular
changes exhibited by the aging gut cells also vary. Aging intestinal smooth
muscle cells exhibit a number of changes in the signalling pathways that regulate
contraction. There is some evidence for age-associated degeneration of neurons
and glia of the enteric nervous system, although enteric neuronal losses are
likely not to be nearly as extensive as previously believed. Aging enteric
neurons have been shown to exhibit a senescence-associated phenotype. Epithelial
stem cells exhibit increased mitochondrial mutation in aging that affects their
progeny in the mucosal epithelium. Changes to the microbiota and intestinal
immune system during aging are likely to contribute to wider aging of the
organism and are increasingly important areas of analysis. How changes of the
different cell types of the gut during aging affect the numerous cellular
interactions that are essential for normal gut functions will be important areas
for future aging research.
PMID- 24352569
TI - Hydrophobic sol-gel channel patterning strategies for paper-based microfluidics.
AB - Hydrophobic sol-gel derived methylsilsesquioxane (MSQ) was compared to wax and
alkylketene dimer (AKD) as barrier materials defining channels in paper-based
microfluidic devices. While all three of the barrier types performed well with
water, only the MSQ barriers were not breached by aggressive cell lysing
solutions and surfactant solutions (SDS, CTAB, Triton X-100). The MSQ barriers
also withstood glycerol, toluene and DMSO whereas all three barrier types were
breached by alcohols. MSQ based devices could be prepared either by direct inkjet
printing of the barriers or by base etching of MSQ impregnated paper. The
functionality of MSQ based devices was demonstrated by formatting a colormetric
sensor for Escherichia coli.
PMID- 24352568
TI - Anxiety-like behavior of mice produced by conditional central expression of the
HIV-1 regulatory protein, Tat.
AB - RATIONALE: Human immunodeficiency virus (HIV) infection is associated with
substantial increases in generalized anxiety. The HIV regulatory protein,
transactivator of transcription (Tat), has been implicated in the
neuropathogenesis related to HIV-1 infection. However, direct examination of the
effect of Tat on behavioral measures of anxiety has not been demonstrated.
OBJECTIVE: To identify whether expression of the Tat1-86 protein exerts dose
dependent and persistent anxiety-like effects in a whole animal model, the GT-tg
bigenic mouse. METHODS: GT-tg mice and C57BL/6J controls were administered
doxycycline in a dose- (0, 50, 100, or 125 mg/kg, i.p., for 7 days) or duration-
(100 mg/kg, i.p., for 0, 1, 3, 5, or 14 days) dependent manner to induce Tat1-86
in brain. Mice were assessed for anxiety-like behavior in an open field, social
interaction, or marble burying task 0, 7, and/or 14 days later. Central
expression of Tat1-86 protein was verified with Western blot analyses. RESULTS:
Doxycycline produced no effects on C57BL/6J controls that lacked the Tat1-86
transgene. Among GT-tg mice, doxycycline (100 mg/kg for 3, 5, or 7 days)
significantly increased anxiety-like behavior in all tasks, commensurate with
enhanced Western blot labeling of Tat1-86 protein in brain, displaying optimal
effects with the 7-day regimen. Greater exposure to doxycycline (either 125 mg/kg
for 7 days or 100 mg/kg for 14 days) impaired locomotor behavior; whereas lower
dosing (below 100 mg/kg) produced only transient increases in anxiety-like
behavior. CONCLUSIONS: Expression of HIV-1-Tat1-86 in GT-tg mouse brain produces
exposure-dependent, persistent increases in anxiety-like behavior.
PMID- 24352570
TI - Multiplex chemiluminescent immunoassay for screening of mycotoxins using photonic
crystal microsphere suspension array.
AB - A novel multiplex chemiluminescent mycotoxin immunoassay suspension array system
was developed by combining the silica photonic crystal microspheres (SPCMs)
encoding technique and a chemiluminescent immunoassay (CLIA) method. The SPCMs
were used as a carrier of the suspension array and encoded by their reflectance
peak positions, which overcome fluorescence photobleaching, and the potential
interference between the encoding fluorescence and detection fluorescence.
Aflatoxin B1 (AFB1), fumonisin B1 (FB1) and ochratoxin A (OTA) artificial
antigens were immobilized on the surfaces of SPCMs by using 3
glycidoxypropyltrimethoxysilane as a linker. Horseradish peroxidase (HRP) was
used as a labeling enzyme for the secondary antibody in the enzyme-catalyze H2O2
luminol chemiluminescence system. The CLIA detection system was easily integrated
with a multifunctional microplate reader and displayed a two to three orders of
magnitude dynamic linear detection range from 0.001 to 1, 0.001 to 1, and 0.01 to
1 ng mL(-1) for AFB1, FB1 and OTA with 50% inhibitory concentrations (IC50) of
0.01, 0.036, and 0.04 ng mL(-1), respectively. The recovery rates are in the
range of 63.5 to 121.6% for the three mycotoxins in three kinds of spiked cereal
samples. The results of detection in 12 naturally contaminated cereal samples
were consistent with that of the classic enzyme-linked immunosorbent assay
(ELISA) method. This proposed system is simple, rapid, low cost and high
throughput for multiplex mycotoxin assay.
PMID- 24352571
TI - Evolution of the average avalanche shape with the universality class.
AB - A multitude of systems ranging from the Barkhausen effect in ferromagnetic
materials to plastic deformation and earthquakes respond to slow external driving
by exhibiting intermittent, scale-free avalanche dynamics or crackling noise. The
avalanches are power-law distributed in size, and have a typical average shape:
these are the two most important signatures of avalanching systems. Here we show
how the average avalanche shape evolves with the universality class of the
avalanche dynamics by employing a combination of scaling theory, extensive
numerical simulations and data from crack propagation experiments. It follows a
simple scaling form parameterized by two numbers, the scaling exponent relating
the average avalanche size to its duration and a parameter characterizing the
temporal asymmetry of the avalanches. The latter reflects a broken time-reversal
symmetry in the avalanche dynamics, emerging from the local nature of the
interaction kernel mediating the avalanche dynamics.
PMID- 24352572
TI - Host and pathogen DNA identification in blood meals of nymphal Ixodes ricinus
ticks from forest parks and rural forests of Poland.
AB - DNA analysis of blood meals from unfed nymphal Ixodes ricinus allows for the
identification of tick host and tick-borne pathogens in the host species. The
recognition of host species for tick larvae and the reservoirs of Borrelia,
Rickettsia and Anaplasma species were simultaneously carried out by analysis of
the blood meals of 880 questing nymphal I. ricinus ticks collected in forest
parks of Szczecin city and rural forests in northwestern Poland that are endemic
areas for Lyme borreliosis. The results obtained from the study indicate that I.
ricinus larvae feed not only on small or medium animals but also on large animals
and they (i.e. roe deer, red deer and wild boars) were the most prevalent in all
study areas as the essential hosts for larvae of I. ricinus. The composition of
medium and small vertebrates (carnivores, rodents, birds and lizards) provided a
more diverse picture depending on study site. The reservoir species that contain
the most pathogens are the European roe deer Capreolus capreolus, in which two
species of Rickettsia and two species of Borrelia were identified, and Sus
scrofa, in which one Rickettsia and three Borrelia species were identified.
Rickettsia helvetica was the most common pathogen detected, and other included
species were the B. burgdorferi s.l. group and B. miyamotoi related to relapsing
fever group. Our results confirmed a general association of B. garinii with birds
but also suggested that such associations may be less common in the transmission
cycle in natural habitats than what was thought previously.
PMID- 24352573
TI - Acute exercises induce disorders of the gastrointestinal integrity in a murine
model.
AB - PURPOSE: Many endurance athletes complain about gastrointestinal (GI) symptoms.
It is assumed that exercise-induced shift of perfusion with consecutive
hypoperfusion of the enteral vascular system leads to an increased GI
permeability and tissue damage. Therefore, the aim of the study was to
investigate permeability, apoptosis, electrogenic ion transport (Isc), and tissue
conductance (Gt) of the small intestine in a murine exercise model. METHODS:
After spirometry, male Swiss CD-1 mice were subjected to an intensive treadmill
exercise (80% VO2max). Sedentary mice served as controls. The small intestine was
removed at several time intervals post-exercise. Apoptotic cells were determined
by the TUNEL method, while fluorescein isothiocyanate dextran permeation
indicated intestinal permeability. The Gt and Isc measurements were carried out
in a modified Ussing chamber. RESULTS: Apoptosis of epithelial cells increased
continuously until 24 h post exercise (0.8 +/- 0.42 versus 39.2 +/- 26.0%; p <
0.05). Compared with the control group the permeability increased 2 h after
exercise (0.47 +/- 0.07 versus 0.67 +/- 0.14 FU/min; p < 0.05). Isc measurements
of the ileum were augmented after 24 h (3.33 +/- 0.56 versus 5.77 +/- 1.16
MUEq/h/cm(2); p < 0.05). At this time the Gt increased as well (28.8 +/- 3.37
versus 32.5 +/- 2.59 mS/cm(2); p < 0.05). CONCLUSION: In the murine exercise
model there is evidence that after intense endurance exercise repair processes
occur in small intestinal epithelial cells, which affect permeability, Gt, and
Isc. The formation of lamellipodia to close the "leaky" tight junctions caused by
apoptosis might be an underlying mechanism.
PMID- 24352575
TI - Shaping and resizing of multifed slot radiators used in conformal microwave
antenna arrays for hyperthermia treatment of large superficial diseases.
AB - It has been recently shown that chestwall recurrence of breast cancer and many
other superficial diseases can be successfully treated with the combination of
radiation, chemotherapy and hyperthermia. Conformal microwave antenna array for
hyperthermia treatment of large area superficial diseases can significantly
increase patient comfort while at the same time facilitate treatment of larger
and more irregularly shaped disease. A large number of small efficient antennas
is preferable for improved control of heating, as the disease can be more
accurately contoured and the lower power requirement correlates with system
reliability, linearity and reduced cost. Thus, starting from the initially
proposed square slot antennas, we investigated new designs for multi-fed slot
antennas of several shapes that maximize slot perimeter while reducing radiating
area, thus increasing antenna efficiency. Simulations were performed with
commercial electromagnetic simulation software packages (Ansoft HFSS) to
demonstrate that the antenna size reduction method is effective for several dual
concentric conductor (DCC) aperture shapes and operating frequencies. The
theoretical simulations allowed the development of a set of design rules for
multi-fed DCC slot antennas that facilitate conformal heat treatments of
irregular size and shape disease with large multi-element arrays. Independently
on the shape, it is shown that the perimeter of 10cm at 915 MHz delivers optimal
radiation pattern and efficiency. While the maximum radiation is obtained for a
circular pattern the rectangular shape is the one that feels more efficiently the
array space.
PMID- 24352574
TI - A phase II study of docetaxel and vinorelbine plus filgrastim for HER-2 negative,
stage IV breast cancer: SWOG S0102.
AB - Docetaxel and vinorelbine have demonstrated Single-agent activity in breast
cancer. Preclinical studies suggest potential synergy between these antitubulin
chemotherapy agents. This study evaluates these drugs in combination in
metastatic breast cancer. Taxane-naive patients with HER-2 negative, stage IV
breast cancer without prior chemotherapy for metastatic disease, were eligible.
Docetaxel (60 mg/m(2)) was given intravenously on Day 1, vinorelbine (27.5
mg/m(2)) intravenously on Days 8 and 15, and filgrastim on Days 2-21 of a 21-day
cycle. The primary study outcome was one-year overall survival (OS), with
secondary outcomes of progression-free survival (PFS), response rate (RR), and
toxicity. Of 95 patients registered, 92 were eligible and received treatment. One
year OS was 74 % (95 % CI 64-82 %) with a median OS of 22.3 months (95 % CI 18.8
31.4 months). One-year PFS was 34 % (95 % CI 24-43 %) with median of 7.2 months
(95 % CI 6.4-10.3). OS at 2 and 3 years were 49 % (95 % CI 38-59 %) and 30 % (95
% CI 21-40 %), respectively. OS was poorer for women with estrogen-receptor
negative disease (n = 32) compared to estrogen-receptor positive (n = 60) (log
rank p = 0.031), but PFS was not significantly different (p = 0.11). RR was 59 %
among the 74 patients with measurable disease. Grade 3 and 4 adverse events were
48 and 16 %, respectively. Grade 4 neutropenia was 12 % and grade 3/4 febrile
neutropenia was 3 %. Common grade 3/4 nonhematologic toxicities were fatigue (14
%), pneumonitis (10 %), and dyspnea (9 %). The combination of docetaxel and
vinorelbine is an active first-line chemotherapy in HER-2 nonoverexpressing,
metastatic breast cancer. This combination is associated with significant
hematologic and nonhematologic toxicity. The safety profile and expense of the
filgrastim limit recommendations for routine use.
PMID- 24352576
TI - Benign FGB (148Lys->Asn, and 448Arg->Lys), and novel causative gamma211Tyr->His
mutation distinguished by time of flight mass spectrometry in a family with
hypofibrinogenaemia.
AB - We describe a novel procedure for the direct analysis of plasma fibrinogen by
HPLC time of flight (TOF) mass spectrometry and apply it to the investigation of
a family with hypofibrinogenaemia. Electrospray TOF analysis provided much higher
resolution than was possible with our previous quadrupole analyser and revealed
three different mass changes within the fibrinogen Bbeta and gamma chains of the
family. It also demonstrated the actual hypofibrinogenaemia phenotype was caused
by an aberrantgamma chain (-23 Da) which was expressed at a diminished ratio of
0.2:1 relative to gamma(A) and co-inherited with a second coequally expressed
Bbeta variant (Bbeta(M) /Bbeta(A), 1:1). Co-segregation was confirmed by gene
analysis that showed the affected father and son had a very rare Bbeta148Lys->Arg
mutation (-14 Da) inherited together with a unique new gamma211Tyr->His mutation
(-26 Da). This latter causative substitution occurs at a site that is absolutely
conserved across all fibrinogen chains and preserved across all species. TOF
analysis also identified a variant Bbeta chain (54,186 Da) that was coequally
expressed with normal Bbeta chains (54,213 Da) in the unaffected mother.
PMID- 24352577
TI - The robot has no role in elective colon surgery.
PMID- 24352578
TI - The influence of transition metal oxides on the kinetics of Li2O2 oxidation in Li
O2 batteries: high activity of chromium oxides.
AB - Reducing the energy loss associated with Li2O2 electrochemical oxidation is
paramount to the development of efficient rechargeable lithium-oxygen (Li-O2)
batteries for practical use. The influence of a series of perovskites with
different eg filling on the kinetics of Li2O2 oxidation was examined using Li2O2
prefilled electrodes. While LaCrO3 is inactive for oxygen evolution upon water
oxidation in alkaline solution, it was found to provide the highest specific
current towards Li2O2 oxidation among all the perovskites examined. Further
exploration of Cr-based catalysts showed that Cr nanoparticles (Cr NP) with an
average particle size of 40 nm, having oxidized surfaces, had comparable surface
area activities to LaCrO3 but much greater mass activities. Unlike Pt/C and Ru/C
that promote electrolyte oxidation in addition to Li2O2 oxidation, no evidence of
enhanced electrolyte oxidation was found for Cr NP relative to Vulcan carbon. X
ray absorption spectroscopy at the O K and Cr L edge revealed a redox process of
Cr(3+) <-> Cr(6+) on the surface of Cr NP upon Li2O2 oxidation, which might be
responsible for the enhanced oxidation kinetics of Li2O2 and the reduced charging
voltages of Li-O2 batteries.
PMID- 24352580
TI - Position of lower wisdom teeth and their relation to the alveolar nerve in
orthodontic patients treated with and without extraction of premolars: a
longitudinal study.
AB - OBJECTIVES: The present longitudinal study aimed to compare changes in the lower
third molar position and nerve involvement in orthodontically treated patients
with and without premolar extractions. MATERIALS AND METHODS: The sample
consisted of pretreatment and posttreatment panoramic radiographs of 349
orthodontically treated patients subdivided into a non-extraction group (n = 263)
and an extraction group (n = 86). Patients did not present dental agenesis in the
lower jaw. The mandibular third molar position was assessed by classifying the
teeth according to Pell and Gregory, Winter, and two new classifications. The
relation between third molars and the mandibular canal was assessed based on
Whaites' classification. The development of third molars was evaluated based on
Demirjian's classification. Data were analyzed using frequency analysis, Mann
Whitney U test, Fisher's exact test, and chi-square testing. RESULTS: There was a
significant difference (p < 0.05) in eruption space between pretreatment and
posttreatment panoramic radiographs for both groups. For pretreatment panoramic
radiographs, chi-square tests revealed no significant differences between both
groups. For posttreatment panoramic radiographs, significant differences appeared
for extraction versus non-extraction patients for Pell and Gregory horizontal
classification, Winter's classification, and a potential relationship between
third molars and the alveolar nerve (p < 0.05). CONCLUSIONS: Orthodontic
treatment without premolar extractions shows significantly more eruption problems
of wisdom teeth than those with premolar extractions. Third molars in the non
extraction group were more frequently found in close relationship to the
mandibular nerve compared to the extraction group. CLINICAL RELEVANCE:
Orthodontists should be aware of the effect of orthodontic treatment on the
development of the lower third molars.
PMID- 24352581
TI - T helper cells from aggressive periodontitis patients produce higher levels of
interleukin-1 beta and interleukin-6 in interaction with Porphyromonas
gingivalis.
AB - OBJECTIVE: In this study, we analyzed the production of Interleukin-1 beta (IL
1beta) and IL-6 by activated CD4+ cells obtained from aggressive periodontitis
(AgP) patients in comparison with healthy subjects (HC). MATERIALS AND METHODS:
CD4+ cells were automatically separated from lymphocytes obtained from peripheral
blood of patients with AgP and healthy controls. Cells were activated for 4, 8,
and 24 h with three different stimuli: anti-CD3/anti-CD28, phytohemagglutinin
(PHA), and Porphyromonas gingivalis (P. gingivalis) outer membrane protein (OMP).
Protein levels were measured in supernatants of activated CD4+ cells by a bead
based immunoassay (CBA). In addition, serum antibodies against P. gingivalis were
determined. Data were analyzed using U test (p < 0.05). RESULTS: T helper cells
of AgP patients activated with P. gingivalis OMP produced higher levels of IL
1beta and IL-6 in comparison with healthy controls (p < 0.05). Neither the
activation with anti-CD3/anti-CD28 nor the activation with PHA showed
significantly different production of IL-1beta and IL-6 by the cells 25 % of
patients and 17 % of controls presented with high serum reactivity to P.
gingivalis. CONCLUSION: In view of these results, it is possible to conclude that
P. gingivalis contributes to the pathogenesis of AgP by inducing high levels of
pro-inflammatory cytokines such as IL-1beta and IL-6 by peripheral CD4+ T helper
cells. CLINICAL RELEVANCE: In accordance with the clinical parameters and the
immunological data, we suggest that full-mouth disinfection with adjunctive
systemic antibiotics might be the anti-infectious non-surgical periodontal
treatment of choice in this type of patients. Microbiological analyses at the
beginning and at the end of the periodontal treatment are recommended. However,
it is necessary to verify these data in longitudinal clinical studies.
PMID- 24352583
TI - A new mussel-inspired polydopamine phototransistor with high photosensitivity:
signal amplification and light-controlled switching properties.
AB - A polydopamine (PDA) thin film with a dense and conformal surface was prepared
under optimized deposition conditions using O2 gas as an oxygen source. The PDA
based organic phototransistors exhibited high photosensitivity and photo
controlled switching properties under light illumination.
PMID- 24352582
TI - Screening for coronary heart disease and diabetes risk in a dental setting.
AB - OBJECTIVES: Diabetes mellitus (DM) and heart disease, among the most prevalent
chronic conditions worldwide, are increasing among younger adults who are unaware
of their risk status. Previous studies in the United States have shown the
efficacy of screening for risk of heart disease and diabetes in a dental setting.
A screening strategy was applied to facilitate early identification of
individuals at increased disease risk in a single Indian dental institute.
METHODS: 158 patients >30 years old, with no reported heart disease or diabetes,
and unaware of any increased disease risk were enrolled. Blood pressure, total
cholesterol, high-density lipoprotein levels and body mass index were collected.
The Framingham Risk Score (FRS) was calculated as an indication of global risk of
developing a coronary heart disease (CHD) event within 10 years; hemoglobin A1c
level was used to determine DM risk. RESULTS: Eleven percent had increased risk
of heart disease (FRS >10%) and 32% had abnormal A1c levels (>5.7%). At least one
risk factor was present in 61 and 39% presented with two or more risk factors.
Hypertension and obesity were the most common risk factors. CONCLUSIONS: The use
of a dental setting in a developing country could serve as a resource for early
identification of patients at increased risk of developing CHD and DM, yet
unaware of their increased risk. The dental setting can also serve as an entry
point into the medical care system by identifying asymptomatic patients at
increased risk of disease and referring these individuals to a primary care
provider.
PMID- 24352584
TI - Hysteretic spin crossover in iron(II) complexes of a new pyridine-triazole
pyrazine ligand is tuned by choice of NCE co-ligand.
AB - A family of three new mononuclear complexes of the general form
[Fe(L(pz))2(NCE)2] has been prepared (L(pz) = 4-p-tolyl-3-(2-pyrazinyl)-5-(2
pyridyl)-1,2,4-triazole; E = S, Se, BH3). All three exhibit spin crossover, in
two cases with hysteresis, with T1/2 being predictably tuned by varying the
coordinated anion.
PMID- 24352585
TI - Identification of proteins involved in Hg-Se antagonism in water hyacinth
(Eichhornia crassipes).
AB - Different studies have established the presence of a proteinaceus complex
involved in Hg-Se agonism/antagonism in plants. In order to identify proteins
involved in this mechanism, water hyacinth plants were divided into groups and
supplemented with Hg, Se and a Hg-Se mixture. Proteins involved were identified
through a screening separation by SEC-ICPMS followed by SAX-ICPMS and then
peptide mapping of selected fractions by nanoLC-ESI-ITMS(2). Determination of
total metal concentration showed that Se inhibits Hg translocation from roots to
aerial compartments of the plant and that Se and Hg are antagonists to each other
in terms of plant toxicity. In roots, stems and leaves Se was distributed mainly
in two molecular mass fractions <670 kDa and ~40 kDa, however, the proportion
between these two fractions was inverted when Hg was co-administered. Hg
throughout the plant was distributed in high and medium molecular mass compounds.
Hg associated with molecules, ranging from <1.5 kDa to 15 kDa, was found in the
root extract of Hg(ii) supplemented plants, but was absent in the root extract of
Se(iv) and Hg(ii) supplemented plants. SAX showed that Hg and Se were mostly not
associated with the same entity, since the complete overlapping of Hg and Se
signals in all the peaks of SEC chromatograms was not observed. Changes in Se and
Hg levels in water hyacinth were more evident in leaves in contrast to other
compartments. Several proteins, possibly associated with either Se or Hg, were
identified in roots, stems and leaves. Most of the identified proteins were
associated with Hg and located in leaves, and these are associated specifically
with chloroplast and mitochondria proteins, related to essential mechanisms in
plants such as photosynthesis, carbon fixation and the electron transport chain.
PMID- 24352586
TI - Locus of control and peer relationships among Caucasian, Hispanic, Asian, and
African American adolescents.
AB - Past research has shown that locus of control plays an important role in a wide
range of behaviors, such as academic achievement and positive social behaviors.
However, little is known about whether locus of control plays the same role in
minority adolescents' peer relationships. The current study examined ethnic
differences in the associations between locus of control and peer relationships
in early adolescence using samples from the Early Childhood Longitudinal Study
(ECLS-K: 5,612 Caucasian, 1,562 Hispanic, 507 Asian, and 908 African-American
adolescents) and the National Education Longitudinal Study (NELS: 8,484
Caucasian, 1,604 Hispanic, and 860 Asian, and 1,228 African American
adolescents). Gender was approximately evenly split in both samples. The results
from the two datasets were highly consistent. Significant interactions between
ethnicity and locus of control indicated that having a more internal locus of
control was particularly important for Caucasian students' peer relationships
(ECLS-K) and social status (NELS), but less so for Asian, Hispanic, and African
American students. Our findings suggest that the role of locus of control in peer
relationship is contingent upon culture.
PMID- 24352587
TI - Distinct intraspecific variations of garlic (Allium sativum L.) revealed by the
exon-intron sequences of the alliinase gene.
AB - Garlic (Allium sativum L.) has been used worldwide as a food and for medicinal
purposes since early times. Garlic cultivars exhibit considerable morphological
diversity despite the fact that they are mostly sterile and are grown only by
vegetative propagation of cloves. Considerable recombination occurs in garlic
genomes, including the genes involved in secondary metabolites. We examined the
genomic DNAs (gDNAs) from garlic, encoding alliinase, a key enzyme involved in
organosulfur metabolism in Allium plants. The 1.7-kb gDNA fragments, covering
three exons (2, 3, and 4) and all four introns, were amplified from total DNAs
prepared from garlic samples produced in Asia and Europe, leading to 73 sequences
in total: Japan (JPN), China (CHN), India (IND), Spain (ESP), and France (FRA).
The exon sequences were highly conserved among all the sequences, probably
reflecting the fully functional alliinase associated with the flavor quality.
Distinct intraspecific variations were detected for all four intron sequences,
leading to the haplotype classifications. A close relationship between JPN and
CHN was observed for all four introns, whereas IND showed a more divergent
distribution. ESP and FRA afforded clearly different variants compared with those
from Asian sequences. The present study provides information that could be useful
in the development of an additional molecular marker for garlic authentication
and quality control.
PMID- 24352588
TI - A targeted/non-targeted screening method for perfluoroalkyl carboxylic acids and
sulfonates in whole fish using quadrupole time-of-flight mass spectrometry and
MS(e).
AB - A new method for measuring perfluoroalkyl contaminants (PFCs) in biological
matrices has been developed. An ultra-high pressure liquid chromatograph equipped
with a quadrupole time-of-flight mass spectrometer (UPLC-QToF) was optimized
using a continuous precursor/product ion monitoring mode. Unlike traditional
targeted studies that isolate precursor/product ion pairs, the current method
alternates between two ionization energy channels to continuously capture
standard electrospray ionization (low energy) and collision induced dissociation
(high energy) spectra. The result is the indiscriminant acquisition of paired low
and high energy spectra for all constituents eluting from the chromatographic
system. This technique was evaluated for the routine analysis of perfluoroalkyl
species. Using this technique, linear perfluoroalkyl carboxylic acids (C4 to C14)
and perfluoroalkyl sulfonates (C4, C6, C8 and C10) exhibited a linear range
spanning over three orders of magnitude and were detectable at levels less than 1
pg on column with a root mean squared signal to noise ratio of 5 to 20. Lake
trout (Salvelinus namaycush) and National Institutes of Standards and Technology
Standard Reference Material 1946 were used to evaluate matrix effects and the
accuracy of this method when applied to a whole fish extract. The current method
was also evaluated as a diagnostic tool to identify unknown PFCs using
experimental fragmentation patterns, mass defect filtering and Kendrick plots.
PMID- 24352589
TI - Cu(I)-MOF: naked-eye colorimetric sensor for humidity and formaldehyde in single
crystal-to-single-crystal fashion.
AB - A porous Cu(I)-MOF was constructed from CuI and 1-benzimidazolyl-3,5-bis(4
pyridyl)benzene. This Cu(I)-MOF can be a highly sensitive naked-eye colorimetric
sensor to successively detect water and formaldehyde species in a single-crystal
to-single-crystal fashion. Solid-state guest-responsive luminescence is also used
to monitor the sensing process.
PMID- 24352590
TI - Forest cutting and impacts on carbon in the eastern United States.
AB - Forest cutting is a major anthropogenic disturbance that affects forest carbon
(C) storage and fluxes. Yet its characteristics and impacts on C cycling are
poorly understood over large areas. Using recent annualized forest inventory
data, we estimated cutting-related loss of live biomass in the eastern United
States was 168 Tg C yr(-1) from 2002 to 2010 (with C loss per unit forest area of
1.07 Mg ha(-1) yr(-1)), which is equivalent to 70% of the total U.S. forest C
sink or 11% of the national annual CO2 emissions from fossil-fuel combustion over
the same period. We further revealed that specific cutting-related C loss varied
with cutting intensities, forest types, stand ages, and geographic locations. Our
results provide new insights to the characteristics of forest harvesting
activities in the eastern United States and highlight the significance of partial
cutting to regional and national carbon budgets.
PMID- 24352591
TI - Structural and biochemical characterization of O-mannose-linked human natural
killer-1 glycan expressed on phosphacan in developing mouse brains.
AB - The human natural killer-1 (HNK-1) carbohydrate comprising a sulfated
trisaccharide (HSO3-3GlcAbeta1-3Galbeta1-4GlcNAc-) is expressed on N-linked and O
mannose-linked glycans in the nervous system and involved in learning and memory
functions. Although whole/core glycan structures and carrier glycoproteins for
the N-linked HNK-1 epitope have been studied, carrier glycoproteins and the
biosynthetic pathway of the O-mannose-linked HNK-1 epitope have not been fully
characterized. Here, using mass spectrometric analyses, we identified the major
carrier glycoprotein of the O-linked HNK-1 as phosphacan in developing mouse
brains and determined the major O-glycan structures having the terminal HNK-1
epitope from partially purified phosphacan. The O-linked HNK-1 epitope on
phosphacan almost disappeared due to the knockout of protein O-mannose beta1,2-N
acetylglucosaminyltransferase 1, an N-acetylglucosaminyltransferase essential for
O-mannose-linked glycan synthesis, indicating that the reducing terminal of the O
linked HNK-1 is mannose. We also showed that glucuronyltransferase-P (GlcAT-P)
was involved in the biosynthesis of O-mannose-linked HNK-1 using the gene
deficient mice of GlcAT-P, one of the glucuronyltransferases for HNK-1 synthesis.
Consistent with this result, we revealed that GlcAT-P specifically synthesized O
linked HNK-1 onto phosphacan using cultured cells. Furthermore, we characterized
the as-yet-unknown epitope of the 6B4 monoclonal antibody (mAb), which was
thought to recognize a unique phosphacan glycoform. The reactivity of the 6B4 mAb
almost completely disappeared in GlcAT-P-deficient mice, and exogenously
expressed phosphacan was selectively recognized by the 6B4 mAb when co-expressed
with GlcAT-P, suggesting that the 6B4 mAb preferentially recognizes O-mannose
linked HNK-1 on phosphacan. This is the first study to show that 6B4 mAb-reactive
O-mannose-linked HNK-1 in the brain is mainly carried by phosphacan.
PMID- 24352592
TI - The role of sleepiness, sleep disorders, and the work environment on heavy
vehicle crashes in 2 Australian states.
AB - Heavy-vehicle driving involves a challenging work environment and a high crash
rate. We investigated the associations of sleepiness, sleep disorders, and work
environment (including truck characteristics) with the risk of crashing between
2008 and 2011 in the Australian states of New South Wales and Western Australia.
We conducted a case-control study of 530 heavy-vehicle drivers who had recently
crashed and 517 heavy-vehicle drivers who had not. Drivers' crash histories,
truck details, driving schedules, payment rates, sleep patterns, and measures of
health were collected. Subjects wore a nasal flow monitor for 1 night to assess
for obstructive sleep apnea. Driving schedules that included the period between
midnight and 5:59 am were associated with increased likelihood of crashing (odds
ratio = 3.42, 95% confidence interval: 2.04, 5.74), as were having an empty load
(odds ratio = 2.61, 95% confidence interval: 1.72, 3.97) and being a less
experienced driver (odds ratio = 3.25, 95% confidence interval: 2.37, 4.46). Not
taking regular breaks and the lack of vehicle safety devices were also associated
with increased crash risk. Despite the high prevalence of obstructive sleep
apnea, it was not associated with the risk of a heavy-vehicle nonfatal, nonsevere
crash. Scheduling of driving to avoid midnight-to-dawn driving and the use of
more frequent rest breaks are likely to reduce the risk of heavy-vehicle
nonfatal, nonsevere crashes by 2-3 times.
PMID- 24352593
TI - Accounting for outcome misclassification in estimates of the effect of
occupational asbestos exposure on lung cancer death.
AB - In studies of the health effects of asbestos, lung cancer death is subject to
misclassification. We used modified maximum likelihood to explore the effects of
outcome misclassification on the rate ratio of lung cancer death per 100 fiber
years per milliliter of cumulative asbestos exposure in a cohort study of textile
workers in Charleston, South Carolina, followed from 1940 to 2001. The standard
covariate-adjusted estimate of the rate ratio was 1.94 (95% confidence interval:
1.55, 2.44), and modified maximum likelihood produced similar results when we
assumed that the specificity of outcome classification was 0.98. With sensitivity
assumed to be 0.80 and specificity assumed to be 0.95, estimated rate ratios were
further from the null and less precise (rate ratio = 2.17; 95% confidence
interval: 1.59, 2.98). In the present context, standard estimates for the effect
of asbestos on lung cancer death were similar to estimates accounting for the
limited misclassification. However, sensitivity analysis using modified maximum
likelihood was needed to verify the robustness of standard estimates, and this
approach will provide unbiased estimates in settings with more misclassification.
PMID- 24352594
TI - Prophylactic central neck disection in papillary thyroid cancer: a consensus
report of the European Society of Endocrine Surgeons (ESES).
AB - BACKGROUND: There remains still no clear answer as to whether or not prophylactic
central compartment neck dissection (pCCND) is indicated for the treatment of
patients with papillary thyroid cancer. METHODS: The published studies, including
single cohort, comparative studies and meta-analysis, were critically appraised.
Aspects beyond postoperative complications and loco-regional recurrence rates in
the analysis, as the impact of pre- and post-ablation thyroglobuline levels,
multifocality, bilaterality and additional risk factors for recurrence, were also
considered. RESULTS: Thirty studies and five meta-analyses were assessed. The
lack of randomized clinical trials on the subject and the heterogeneity of study
populations are the main limiting factors to draw clear conclusions, and a
comprehensive list of bias sources has been identified. Recent comparative
studies and systematic reviews all associate the pCCND with higher proportions of
temporary postoperative hypocalcemia but not with significantly higher permanent
hypoparathyroidism, recurrent laryngeal nerve injury or permanent vocal cord
paralysis. The risk of recurrence appears to be reduced after pCCND, and the
number of patients needed to treat to avoid a recurrence is between 20 and 31.
CONCLUSIONS: It is suggested that routine level 6 prophylactic dissections should
be risk-stratified. Larger tumours (T3, T4), patients aged 45 years and older or
15 years and younger, male patients, patients with bilateral or multifocal
tumours, and patients with known involved lateral lymph nodes could all be
candidates for routine unilateral level 6 dissection. The operation should be
limited to surgeons who have the available expertise and experience.
PMID- 24352596
TI - Development of an automated model to predict the risk of elderly emergency
medical admissions within a month following an index hospital visit: a Hong Kong
experience.
AB - OBJECTIVES: To develop an automated risk prediction model to identify elderly
patients at high risk of emergency admission to medical wards within 28 days
following an index hospital visit. METHODS: A retrospective data analysis of 41
hospitals and 48 specialist outpatient clinics in Hong Kong. The study subjects
were elderly patients aged 65 years or above, who had index hospital visit(s) in
the year of 2005, which included hospitalizations at medical wards and
attendances at the accident and emergency departments or specialist outpatient
clinics for medical conditions. Multiple logistic regression was used to estimate
the risk of emergency medical admission in 28 days after an index hospital visit.
Model validation was performed against the complete cohort in 2006. RESULTS: Over
a million of episodes were included in the derivation cohort. A total of 14
predictor variables included patient socio-demographics, service utilization in
the previous year, presence and number of chronic diseases and type of index
episode. The model has a good discriminative ability with the area under receiver
operating characteristic curve at 0.819 and 0.824 for the derivation and
validation cohorts, respectively. The model has a sensitivity of 70.3 per cent,
specificity of 78.4 per cent, positive predictive value of 21.7 per cent and
negative predictive value of 96.9 per cent. CONCLUSION: This simple, accurate and
objective risk prediction model has been computerized into an automated screening
tool to recruit high-risk elderly patients discharged from all public hospitals
in Hong Kong into the Community Health Call Centre service with an aim to prevent
avoidable hospitalizations.
PMID- 24352595
TI - Left ventricular twist during dobutamine stress echocardiography after acute
myocardial infarction: association with reverse remodeling.
AB - Left ventricular (LV) twist is emerging as a marker of global LV contractility
after acute myocardial infarction (AMI). This study aimed to describe stress
induced changes in LV twist during dobutamine stress echocardiography (DSE) after
AMI and investigate their association with LV reverse remodeling at 6 months
follow-up. In 82 consecutive first AMI patients (61 +/- 12 years, 85 % male)
treated with primary percutaneous coronary intervention, DSE was performed at 3
months follow-up. Two-dimensional speckle-tracking-derived apical and basal
rotation and LV twist were calculated at rest, low- and peak-dose stages. LV
reverse remodeling was defined as >=10 % decrease in LV end-systolic volume
between baseline and 6 months follow-up. Patterns of LV twist response on DSE
consisted of either a progressive increase throughout each stage (n = 18), an
increase at either low- or peak-dose (n = 53) or no significant increase (n =
11). LV reverse remodeling occurred in 28 (34 %) patients, who showed
significantly higher peak-dose LV twist (8.51 degrees vs. 6.69 degrees , p =
0.03) and more frequently progressive LV twist increase from rest to peak-dose
(39 vs. 13 %, p < 0.01) compared to patients without reverse remodeling.
Furthermore, increase in LV twist from rest to peak-dose was the only independent
predictor of LV reverse remodeling at 6 months follow-up (OR 1.3, 95 % CI 1.1
1.5, p = 0.005). Both the pattern of progressive increase in LV twist and the
stress-induced increment in LV twist on DSE are significantly associated with LV
reverse remodeling at 6 month follow-up after AMI, suggesting its potential use
as a novel marker of contractile reserve.
PMID- 24352597
TI - Accessibility, usability, and usefulness of a Web-based clinical decision support
tool to enhance provider-patient communication around Self-management TO Prevent
(STOP) Stroke.
AB - This article reports redesign strategies identified to create a Web-based user
interface for the Self-management TO Prevent (STOP) Stroke Tool. Members of a
Stroke Quality Improvement Network (N = 12) viewed a visualization video of a
proposed prototype and provided feedback on implementation barriers/facilitators.
Stroke-care providers (N = 10) tested the Web-based prototype in think-aloud
sessions of simulated clinic visits. Participants' dialogues were coded into
themes. Access to comprehensive information and the automated
features/systematized processes were the primary accessibility and usability
facilitator themes. The need for training, time to complete the tool, and
computer-centric care were identified as possible usability barriers. Patient
accountability, reminders for best practice, goal-focused care, and
communication/counseling themes indicate that the STOP Stroke Tool supports the
paradigm of patient-centered care. The STOP Stroke Tool was found to prompt
clinicians on secondary stroke-prevention clinical-practice guidelines,
facilitate comprehensive documentation of evidence-based care, and support
clinicians in providing patient-centered care through the shared decision-making
process that occurred while using the action-planning/goal-setting feature of the
tool.
PMID- 24352598
TI - Treating glaucoma: the not-so-nice guidance.
PMID- 24352599
TI - Authors' response: A randomised controlled trial of alcohol delamination and
phototherapeutic keratectomy for the treatment of recurrent corneal erosion
syndrome.
PMID- 24352600
TI - Authors' response: A randomised controlled trial of alcohol delamination and
phototherapeutic keratectomy for the treatment of recurrent corneal erosion
syndrome.
PMID- 24352601
TI - Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the
american college of surgeons national surgical quality improvement program.
AB - IMPORTANCE: Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive
surgery have been shown to benefit selected patients with peritoneal
carcinomatosis. However, these procedures are associated with high morbidity and
mortality. Available data investigating the outcomes of HIPEC are mostly limited
to single-center studies. To date, there have been few large-scale studies
investigating the postoperative outcomes of HIPEC. OBJECTIVE: To determine the
associated 30-day morbidity and mortality of cytoreductive surgery-HIPEC in the
treatment of metastatic and primary peritoneal cancer in American College of
Surgeons National Surgical Quality Improvement Program centers. DESIGN, SETTING,
AND PARTICIPANTS: A retrospective review of HIPEC cases performed for primary and
metastatic peritoneal cancer diagnoses was conducted. The cytoreductive surgical
procedures were sampled, and disease processes were identified. Patient
demographics, intraoperative occurrences, and postoperative complications were
reviewed from the American College of Surgeons National Surgical Quality
Improvement Program from 2005-2011. MAIN OUTCOMES AND MEASURES: Thirty-day
mortality and morbidity. RESULTS: Of the cancers identified among the 694 sampled
cases, 14% of patients had appendiceal cancer, 11% had primary peritoneal cancer,
and 8% had colorectal cancer. The American Society of Anesthesiologists
classification was 3 for 70% of patients. The average operative time was 7.6
hours, with 15% of patients requiring intraoperative transfusions. Postoperative
bleeding (17%), septic shock (16%), pulmonary complications (15%), and organ
space infections (9%) were the most prevalent postoperative complications. The
average length of stay was 13 days, with a 30-day readmission rate of 11%. The
rate of reoperation was 10%, with an overall mortality rate of 2%. CONCLUSIONS
AND RELEVANCE: American College of Surgeons National Surgical Quality Improvement
Program hospitals performing HIPEC have acceptable rates of morbidity and
mortality.
PMID- 24352603
TI - Extracellular activities of aminoacyl-tRNA synthetases: new mediators for cell
cell communication.
AB - Over the last decade, many reports have discussed aminoacyl-tRNA synthetases
(ARSs) in extracellular space. Now that so many of them are known to be secreted
with distinct activities in the broad range of target cells including
endothelial, various immune cells, and fibroblasts, they need to be classified as
a new family of extracellular signal mediators. In this chapter the identity of
the secreted ARSs, receptors, and their physiological and pathological
implications will be described.
PMID- 24352604
TI - Intrinsic cardiac adrenergic (ICA) cell density and MAO-A activity in failing rat
hearts.
AB - The efficiency (work/oxygen consumption) of isolated papillary muscles from
failing hearts is reduced. We investigated whether this can be due to an increase
of intrinsic cardiac adrenergic (ICA) cell density. The number of ICA cells in
the septum and both ventricular walls was determined by tyrosine hydroxylase
immunohistochemistry in rats with monocrotaline-induced pulmonary hypertension.
We found that the number of ICA cells is about 200,000 per rat heart. ICA cell
density was significantly lower in right ventricular myocardium of hypertrophied
hearts (P < 0.01). MAO-A enzyme histochemistry and inhibition experiments with
clorgyline in papillary muscles were performed to localize the enzyme and to
determine its oxygen consumption. Upregulation of MAO-A was found in the right
ventricular wall and papillary muscles of failing hearts (P = 0.018). A positive
correlation between ICA cell density and MAO-A activity was absent. Clorgyline (2
MUM) decreased the basal rate of oxygen consumption of right ventricular
papillary muscles by 65 MUM O(2)/s (P = 0.027). This rate can only be maintained
for several seconds judging from the catecholamine content of the preparations
reported previously. High ICA cell activity rather than density and/or recycling
of oxidized catecholamines are discussed as alternative explanations for the low
myocardial efficiency in experimental pulmonary hypertension.
PMID- 24352605
TI - Codon-reading specificities of mitochondrial release factors and translation
termination at non-standard stop codons.
AB - A key feature of mitochondrial translation is the reduced number of transfer RNAs
and reassignment of codons. For human mitochondria, a major unresolved problem is
how the set of stop codons are decoded by the release factors mtRF1a and mtRF1.
Here we present three-dimensional structural models of human mtRF1a and mtRF1
based on their homology to bacterial RF1 in the codon recognition domain, and the
strong conservation between mitochondrial and bacterial ribosomal RNA in the
decoding region. Sequence changes in the less homologous mtRF1 appear to be
correlated with specific features of the mitochondrial rRNA. Extensive computer
simulations of the complexes with the ribosomal decoding site show that both
mitochondrial factors have similar specificities and that neither reads the
putative vertebrate stop codons AGA and AGG. Instead, we present a structural
model for a mechanism by which the ICT1 protein causes termination by sensing the
presence of these codons in the A-site of stalled ribosomes.
PMID- 24352606
TI - Non-selective ion channel activity of polymorphic human islet amyloid polypeptide
(amylin) double channels.
AB - Fundamental understanding of ion channel formation by amyloid peptides, which is
strongly linked to cell toxicity, is very critical for (pre)clinical treatment of
neurodegenerative diseases. Here, we combine atomistic simulations and
experiments to demonstrate a broad range of conformational states of hIAPP double
channels in lipid membranes. All individual channels display high selectivity for
Cl(-) ions over cations, but the co-existence of polymorphic double channels of
different conformations and orientations with different populations determines
the non-ionic selectivity nature of the channels, which is different from the
typical amyloid-beta channels that exhibit Ca(2+) selective ion-permeable
characteristics. This work provides a more complete physicochemical mechanism of
amyloid-channel-induced toxicity.
PMID- 24352607
TI - Joint position sense during a reaching task improves at targets located closer to
the head but is unaffected by instruction.
AB - The purpose of the present study was twofold. Our first purpose was to test
whether joint position sense is similar under instructions to memorize hand
position and instructions to memorize shoulder and elbow angles. We hypothesized
that instructions to memorize hand position would produce smaller errors due to
evidence suggesting that the CNS directly determines hand position but indirectly
determines joint angles from proprioceptive information. Our second purpose was
to assess biases in joint position sense at various joint angles in a sagittal
workspace. We hypothesized that akin to previous single-joint investigations, the
shoulder and elbow would demonstrate better joint position sense as joint angles
approached 90 degrees during our multi-joint task. Sixteen healthy and right
hand-dominant subjects participated in the present investigation. Subjects were
required to actively position their right upper extremity to one of three targets
for a memorization period. After returning to the rest position, subjects then
actively repositioned back into the target. We did not find evidence of a
substantial difference in joint position sense between instructions to memorize
the hand position or joint angle. This finding, when considered in conjunction
with other evidence, suggests that studies employing either a joint angle
protocol or a hand estimation protocol likely produce results that are similar
enough to be compared. Proprioception has been shown to be non-uniform across a
two-dimensional horizontal workspace. The present investigation provides evidence
that proprioception is also non-uniform across a two-dimensional sagittal
workspace. Specifically, angular errors decrease as upper extremity joint angles
approach 90 degrees of flexion and endpoint errors decrease as targets are
located increasingly closer to the head.
PMID- 24352608
TI - Motor synergies during manual tracking differ between familiar and unfamiliar
trajectories.
AB - Synergistic control of the effector space allows high precision in task-relevant
degrees of freedom, while noise is limited to task-irrelevant degrees of freedom.
The present study investigates whether this typical structure of the variance
covariance matrix of the joint angles during manual tracking differs between
familiar and unfamiliar trajectories. Subjects tracked a target moving in 2D on a
graphics tablet with a hand-held pen, while their arm movements were not
restricted. Subjects familiarized themselves with one target trajectory during an
initial training block with 40 periodic trials. In the following test block, this
familiar trajectory and several unfamiliar trajectories were presented in a mixed
block design to study prediction effects at the level of endpoint and joint
trajectories. The differences in the synergistic control of arm movements were
analyzed using the "uncontrolled manifold method." The results showed smaller
variances and weaker motor synergies during tracking of familiar trajectories
than during tracking of unfamiliar trajectories. The decrease in the synergy
index was due to a stronger decrease in the variance irrelevant than of the
variance relevant for pen position. In the context of motor control theory, these
results suggest that tracking movements on familiar and unfamiliar target
trajectories do not only differ in the available knowledge about target location
but also apply different strategies to control the effector space.
PMID- 24352609
TI - Vertical saccades in children: a developmental study.
AB - There are no studies exploring the development of vertical saccades in large
populations of children. In this study, we examined the development of vertical
saccades in sixty-nine children. Binocular eye movements were recorded using an
infrared video oculography system [Mobile EBT((r)), e(ye)BRAIN], and movements
from both eyes had been analyzed. The gain and the peak velocity of vertical
saccades show an up-down asymmetry. Latency value decreases with the age of
children, and it does not depend on the direction of the saccades; in contrast,
the gain and the peak velocity values of vertical saccades are stable during
childhood. We suggest that the up-down asymmetry is developed early, or is
innate, in humans. Latencies of vertical saccades develop with the age of
children, in relationship with the development of the cortical network
responsible for the saccade preparation. In contrast, the precision and the peak
velocity are not age-dependent as they are controlled by the cerebellum and
brainstem structures.
PMID- 24352610
TI - Teleporting photonic qudits using multimode quantum scissors.
AB - Teleportation plays an important role in the communication of quantum information
between the nodes of a quantum network and is viewed as an essential ingredient
for long-distance Quantum Cryptography. We describe a method to teleport the
quantum information carried by a photon in a superposition of a number d of light
modes (a "qudit") by the help of d additional photons based on transcription. A
qudit encoded into a single excitation of d light modes (in our case Laguerre
Gauss modes which carry orbital angular momentum) is transcribed to d single-rail
photonic qubits, which are spatially separated. Each single-rail qubit consists
of a superposition of vacuum and a single photon in each one of the modes. After
successful teleportation of each of the d single-rail qubits by means of "quantum
scissors" they are converted back into a qudit carried by a single photon which
completes the teleportation scheme.
PMID- 24352611
TI - Spiking Neural Network Decoder for Brain-Machine Interfaces.
AB - We used a spiking neural network (SNN) to decode neural data recorded from a 96
electrode array in premotor/motor cortex while a rhesus monkey performed a point
to-point reaching arm movement task. We mapped a Kalman-filter neural prosthetic
decode algorithm developed to predict the arm's velocity on to the SNN using the
Neural Engineering Framework and simulated it using Nengo, a freely available
software package. A 20,000-neuron network matched the standard decoder's
prediction to within 0.03% (normalized by maximum arm velocity). A 1,600-neuron
version of this network was within 0.27%, and run in real-time on a 3GHz PC.
These results demonstrate that a SNN can implement a statistical signal
processing algorithm widely used as the decoder in high-performance neural
prostheses (Kalman filter), and achieve similar results with just a few thousand
neurons. Hardware SNN implementations-neuromorphic chips-may offer power savings,
essential for realizing fully-implantable cortically controlled prostheses.
PMID- 24352612
TI - Will there be a good general surgeon when you need one?
AB - INTRODUCTION: The Public Policy & Advocacy Committee sponsored the panel on the
topic of "Will There Be a General Surgeon When You Need One?" at the 2012 Annual
Meeting of the SSAT. The panel of experts was convened to formulate
recommendations to help general surgeons adapt to the changing landscape which
will undoubtedly affect the practice of surgery in the future. The invited
speakers were Drs. David Hoyt, Carlos Pellegrini, Kaye M. Reid-Lombardo, and
David Rattner. The session was moderated by Drs. Ross Goldberg and Tara Kent. The
invited presentations and audience commentary are the basis of this manuscript.
PMID- 24352613
TI - Rectal prolapse: an overview of clinical features, diagnosis, and patient
specific management strategies.
AB - Rectal prolapse can present in a variety of forms and is associated with a range
of symptoms including pain, incomplete evacuation, bloody and/or mucous rectal
discharge, and fecal incontinence or constipation. Complete external rectal
prolapse is characterized by a circumferential, full-thickness protrusion of the
rectum through the anus, which may be intermittent or may be incarcerated and
poses a risk of strangulation. There are multiple surgical options to treat
rectal prolapse, and thus care should be taken to understand each patient's
symptoms, bowel habits, anatomy, and pre-operative expectations. Preoperative
workup includes physical exam, colonoscopy, anoscopy, and, in some patients, anal
manometry and defecography. With this information, a tailored surgical approach
(abdominal versus perineal, minimally invasive versus open) and technique
(posterior versus ventral rectopexy +/- sigmoidectomy, for example) can then be
chosen. We propose an algorithm based on available outcomes data in the
literature, an understanding of anorectal physiology, and expert opinion that can
serve as a guide to determining the rectal prolapse operation that will achieve
the best possible postoperative outcomes for individual patients.
PMID- 24352614
TI - Dissecting the contributions of beta-hairpin tyrosine pairs to the folding and
stability of long-lived human gammaD-crystallins.
AB - Ultraviolet-radiation-induced damage to and aggregation of human lens crystallin
proteins are thought to be a significant pathway to age-related cataract. The
aromatic residues within the duplicated Greek key domains of gamma- and beta
crystallins are the main ultraviolet absorbers and are susceptible to direct and
indirect ultraviolet damage. The previous site-directed mutagenesis studies have
revealed a striking difference for two highly conserved homologous beta-hairpin
Tyr pairs, at the N-terminal domain (N-td) and C-terminal domain (C-td),
respectively, in their contribution to the overall stability of HgammaD-Crys, but
why they behave so differently still remains a mystery. In this paper, we
systematically investigated the underlying molecular mechanism and detailed
contributions of these two Tyr pairs with large scale molecular dynamics
simulations. A series of different tyrosine-to-alanine pair(s) substitutions were
performed in either the N-td, the C-td, or both. Our results suggest that the
Y45A/Y50A pair substitution in the N-td mainly affects the stability of the N-td
itself, while the Y133A/Y138A pair substitution in the C-td leads to a more
cooperative unfolding of both N-td and C-td. The stability of motif 2 in the N-td
is mainly determined by the interdomain interface, while motif 1 in the N-td or
motifs 3 and 4 in the C-td are mainly stabilized by the intradomain hydrophobic
core. The damage to any tyrosine pair(s) can directly introduce some apparent
water leakage to the hydrophobic core at the interface, which in turn causes a
serious loss in the stability of the N-td. However, for the C-td substitutions,
it may further impair the stable "sandwich-like" Y133-R167-Y138 cluster (through
cation-pi interactions) in the wild-type, thus causing the loop regions near the
residue A138 to undergo large fluctuations, which in turn results in the
intrusion of water into the hydrophobic core of the C-td and induces the C-td to
lose its stability. These findings help resolve the "mystery" on why these two
Tyr pairs display such a striking difference in their contributions to the
overall protein stability despite their highly homologous nature.
PMID- 24352615
TI - Developmental endothelial locus-1 attenuates complement-dependent phagocytosis
through inhibition of Mac-1-integrin.
PMID- 24352616
TI - PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to
hepatocarcinogenesis.
AB - BACKGROUND: Mounting epidemiological evidence supports a role for phosphatase and
tensin homologue (PTEN)-T cell leukaemia 1 (Tcl1) signalling deregulation in
hepatocarcinogenesis. OBJECTIVE: To determine the molecular and biochemical
mechanisms by which the PTEN/Tcl1 axis regulates the pentose phosphate pathway
(PPP) in hepatocellular carcinoma (HCC). METHODS: We compared levels of PTEN and
glucose-6-phosphate dehydrogenase (G6PD) mRNA in human HCC and healthy liver
tissue. We measured PPP flux, glucose consumption, lactate production,
nicotinamide adenine dinucleotide phosphate (NADPH) levels and lipid
accumulation. We investigated the PTEN/Tcl1 axis using molecular biology,
biochemistry and mass spectrometry analysis. We assessed proliferation, apoptosis
and senescence in cultured cells, and tumour formation in mice. RESULTS: We
showed that PTEN inhibited the PPP pathway in human liver tumours. Through the
PPP, PTEN suppressed glucose consumption and biosynthesis. Mechanistically, the
PTEN protein bound to G6PD, the first and rate-limiting enzyme of the PPP and
prevented the formation of the active G6PD dimer. Tcl1, a coactivator for Akt,
reversed the effects of PTEN on biosynthesis. Tcl1 promoted G6PD activity and
also increased G6PD pre-mRNA splicing and protein expression in a heterogeneous
nuclear ribonucleoprotein (hnRNPK)-dependent manner. PTEN also formed a complex
with hnRNPK, which inhibited G6PD pre-mRNA splicing. Moreover, PTEN inactivated
Tcl1 via glycogen synthase kinase-3beta (GSK3beta)-mediated phosphorylation.
Importantly, Tcl1 knockdown enhanced the sensitivity of HCC to sorafenib, whereas
G6PD knockdown inhibited hepatocarcinogenesis. CONCLUSIONS: These results
establish the counteraction between PTEN and Tcl1 as a key mechanism that
regulates the PPP and suggest that targeting the PTEN/Tcl1/hnRNPK/G6PD axis could
open up possibilities for therapeutic intervention and improve the prognosis of
patients with HCC.
PMID- 24352618
TI - DNA damage and effects on antioxidative enzymes in earthworm (Eisenia fetida)
induced by flumorph.
AB - Flumorph is an Oomycete fungicide, which is used extensively as an effective
fungicide in vegetables and fruits, but little is known about its effect on
nontarget soil organisms. In the present study, biochemical responses including
changes in the activity of antioxidative enzymes catalase (CAT), superoxide
dismutase (SOD), glutathione-S-transferase (GST), malondialdehyde (MDA), and DNA
damage induced by flumorph were investigated in earthworms (Eisenis fetida). The
CAT concentrations were stimulated at 5.0 mg kg(-1) over 28 days and inhibited at
10 and 20 mg kg(-1), except 10 mg kg(-1) on days 21 and 28 compared with the
controls. The overall SOD activities were inhibited except 5 mg kg(-1) on day 28
and 10 mg kg(-1) on days 7 and 14. Meanwhile, the GST activities were stimulated
on day 7 and decreased on the other days in summary. The MDA activities were
increased notably at 5, 10, and 20 mg kg(-1) after 14 days. Clear dose-dependent
DNA damage to Eisenia fetida was observed by olive tail moments in comet assay
compared with controls. The results demonstrate that flumorph induces oxidative
stress and DNA damage to earthworms, and the effects may be the important
mechanisms of its toxicity.
PMID- 24352617
TI - The effectiveness and risks of bariatric surgery: an updated systematic review
and meta-analysis, 2003-2012.
AB - IMPORTANCE: The prevalence of obesity and outcomes of bariatric surgery are well
established. However, analyses of the surgery impact have not been updated and
comprehensively investigated since 2003. OBJECTIVE: To examine the effectiveness
and risks of bariatric surgery using up-to-date, comprehensive data and
appropriate meta-analytic techniques. DATA SOURCES: Literature searches of
Medline, Embase, Scopus, Current Contents, Cochrane Library, and
Clinicaltrials.gov between 2003 and 2012 were performed. STUDY SELECTION:
Exclusion criteria included publication of abstracts only, case reports, letters,
comments, or reviews; animal studies; languages other than English; duplicate
studies; no surgical intervention; and no population of interest. Inclusion
criteria were a report of surgical procedure performed and at least 1 outcome of
interest resulting from the studied surgery was reported: comorbidities,
mortality, complications, reoperations, or weight loss. Of the 25,060 initially
identified articles, 24,023 studies met the exclusion criteria, and 259 met the
inclusion criteria. DATA EXTRACTION AND SYNTHESIS: A review protocol was followed
throughout. Three reviewers independently reviewed studies, abstracted data, and
resolved disagreements by consensus. Studies were evaluated for quality. MAIN
OUTCOMES AND MEASURES: Mortality, complications, reoperations, weight loss, and
remission of obesity-related diseases. RESULTS: A total of 164 studies were
included (37 randomized clinical trials and 127 observational studies). Analyses
included 161,756 patients with a mean age of 44.56 years and body mass index of
45.62. We conducted random-effects and fixed-effect meta-analyses and meta
regression. In randomized clinical trials, the mortality rate within 30 days was
0.08% (95% CI, 0.01%-0.24%); the mortality rate after 30 days was 0.31% (95% CI,
0.01%-0.75%). Body mass index loss at 5 years postsurgery was 12 to 17. The
complication rate was 17% (95% CI, 11%-23%), and the reoperation rate was 7% (95%
CI, 3%-12%). Gastric bypass was more effective in weight loss but associated with
more complications. Adjustable gastric banding had lower mortality and
complication rates; yet, the reoperation rate was higher and weight loss was less
substantial than gastric bypass. Sleeve gastrectomy appeared to be more effective
in weight loss than adjustable gastric banding and comparable with gastric
bypass. CONCLUSIONS AND RELEVANCE: Bariatric surgery provides substantial and
sustained effects on weight loss and ameliorates obesity-attributable
comorbidities in the majority of bariatric patients, although risks of
complication, reoperation, and death exist. Death rates were lower than those
reported in previous meta-analyses.
PMID- 24352619
TI - [Indication: scientific and ethical basis of medical practice].
AB - The medical indication provides a rational foundation for treatment decisions. An
indication can be defined as the reasonable professional judgement that a medical
procedure is suitable and useful to reach a specific therapeutic goal with a
certain probability. An indication includes empirical, causal and purposive
considerations and justifications, and a scrutiny of the individual case. This
ensures that medical aspects of the patient, therapeutic goals and evidence-based
knowledge are integrated and represented in the indication. An indication
justifies a treatment proposal to the patient, which may only be carried out
after a procedure of informed consent. Indications can be considered as the
ethical basis of treatment decisions and as the heart of professionalism:
indications should be used as a professional tool to protect against irrational
therapeutic expectations, while ensuring the patient's right for reasonable
treatment. In health care that is increasingly shaped by economic constraints,
conscientious indications ensure the professional and ethical basis of medical
treatment decisions.
PMID- 24352620
TI - [Dying in the intensive care unit].
AB - Modern intensive care is responsible both for curative interventions in critical
health situations and palliative terminal care for the dying ICU patient. By
applying an integrated ethics approach, this article examines organizational and
cultural factors shaping good terminal care in the ICU. Starting with a
reflection on what it means to be human, ethical goals for care of the dying are
formulated. Among them, the article focuses on practices ensuring a dignified
dying process, on the structured engagement of patients' families, on respecting
cultural and spiritual values, and on a clinical pathway for terminal care as an
institutional framework. In conclusion, it becomes evident that good terminal
care in the ICU not only depends on ethically sound decisions on withholding or
withdrawing medical interventions but also on organizational and cultural aspects
which must be acknowledged and shaped.
PMID- 24352621
TI - [2014: activation of OPS 8-980 "Complex intensive care treatment" by DIMDI].
PMID- 24352622
TI - Rate of return to pitching and performance after Tommy John surgery in Major
League Baseball pitchers.
AB - BACKGROUND: Medial ulnar collateral ligament (UCL) reconstruction is a common
procedure performed on Major League Baseball (MLB) pitchers in the United States.
PURPOSE: To determine (1) the rate of return to pitching (RTP) in the MLB after
UCL reconstruction, (2) the RTP rate in either the MLB and minor league combined,
(3) performance after RTP, and (4) the difference in the RTP rate and performance
between pitchers who underwent UCL reconstruction and matched controls without
UCL injuries. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Major
League Baseball pitchers with symptomatic medial UCL deficiency who underwent UCL
reconstruction were evaluated. All player, elbow, and surgical demographic data
were analyzed. Controls matched by age, body mass index, position, handedness,
and MLB experience and performance were selected from the MLB during the same
years as those undergoing UCL reconstruction. An "index year" was designated for
controls, analogous to the UCL reconstruction year in cases. Return to pitching
and performance measures in the MLB were compared between cases and controls.
Student t tests were performed for analysis of within-group and between-group
variables, respectively. RESULTS: A total of 179 pitchers with UCL tears who
underwent reconstruction met the inclusion criteria and were analyzed. Of these,
148 pitchers (83%) were able to RTP in the MLB, and 174 pitchers were able to RTP
in the MLB and minor league combined (97.2%), while only 5 pitchers (2.8%) were
never able to RTP in either the MLB or minor league. Pitchers returned to the MLB
at a mean 20.5 +/- 9.72 months after UCL reconstruction. The length of career in
the MLB after UCL reconstruction was 3.9 +/- 2.84 years, although 56 of these
patients were still currently actively pitching in the MLB at the start of the
2013 season. The revision rate was 3.9%. In the year before UCL reconstruction,
pitching performance declined significantly in the cases versus controls in the
number of innings pitched, games played, and wins and the winning percentage (P <
.05). After surgery, pitchers showed significantly improved performance versus
before surgery (fewer losses, a lower losing percentage, lower earned run average
[ERA], threw fewer walks, and allowed fewer hits, runs, and home runs) (P < .05).
Comparisons between cases and controls for the time frame after UCL
reconstruction (cases) or the index year (controls) demonstrated that cases had
significantly (P < .05) fewer losses per season and a lower losing percentage. In
addition, cases had a significantly lower ERA and allowed fewer walks and hits
per inning pitched. CONCLUSION: There is a high rate of RTP in professional
baseball after UCL reconstruction. Performance declined before surgery and
improved after surgery. When compared with demographic-matched controls, patients
who underwent UCL reconstruction had better results in multiple performance
measures. Reconstruction of the UCL allows for a predictable and successful
return to the MLB.
PMID- 24352623
TI - Bringing the MCH Life Course Perspective to life.
PMID- 24352624
TI - Bringing sexual and reproductive health in the urban contexts to the forefront of
the development agenda: the case for prioritizing the urban poor.
AB - Estimates suggest that over 90 % of population increase in the least developed
countries over the next four decades will occur in urban areas. These increases
will be driven both by natural population growth and rural-urban migration.
Moreover, despite its status as the world's least urbanized region, the urban
population in the sub-Saharan Africa region is projected to increase from under
40 % currently to over 60 % by 2050. Currently, approximately 70 % of all urban
residents in the region live in slums or slum-like conditions. Sexual and
reproductive health (SRH) risks for the urban poor are severe and include high
rates of unwanted pregnancies, sexually transmitted infections, and poor maternal
and child health outcomes. However, the links between poverty, urbanization, and
reproductive health priorities are still not a major focus in the broader
development agenda. Building on theoretical and empirical data, we show that SRH
in urban contexts is critical to the development of healthy productive urban
populations and, ultimately, the improvement of quality of life. We posit that a
strategic focus on the sexual and reproductive health of urban residents will
enable developing country governments achieve international goals and national
targets by reducing health risks among a large and rapidly growing segment of the
population. To that end, we identify key research, policy and program
recommendations and strategies required for bringing sexual and reproductive
health in urban contexts to the forefront of the development agenda.
PMID- 24352625
TI - Prenatal and postnatal maternal mental health and school-age child development: a
systematic review.
AB - One in six children entering school experiences developmental delay. Maternal
mental health represents one of the earliest, modifiable influences in a child's
life. The objective of the review was to evaluate the association between
maternal mental health and school-age child development, and we hypothesized
there would be a negative association. Five databases were searched (Embase,
CINAHL, Eric, PsycInfo, Medline). Key journals and reference lists were hand
searched. Two reviewers assessed studies based on inclusion criteria: (1) the
exposure was any form of maternal mental health occurring during pregnancy or
postpartum periods; (2) the outcome was child development (>48 months to 8
years); (3) the study recruited participants from developed countries; and (4)
publication was in English between January, 1990 and December, 2012.
Disagreements were resolved by consensus. Study quality was assessed by two
reviewers using the Scottish Intercollegiate Guideline Network and disagreements
were resolved by consensus. Data extraction was conducted by one reviewer using
standardized forms. Maternal mental health problems in pregnancy and/or the
postpartum period increased the likelihood that school-age children experienced
suboptimal global, behavioral, cognitive, and socio-emotional development. The
findings highlight the need for maternal mental health assessment during the
prenatal, postnatal, and early childhood periods.
PMID- 24352626
TI - The impacts of health insurance coverage on access to healthcare in children
entering kindergarten.
AB - To examine access to healthcare and health outcomes for kindergartners as they
relate to insurance status and type. For the 2008, 2009, and 2010 school years,
surveys were distributed to parents with a child entering kindergarten in the
state of Nevada. Surveys asked parents to provide information about their child
concerning their insurance status, routine medical care, medical conditions, and
health behaviors. Compared to their insured peers, uninsured kindergartners were
less likely to have had a check-up in the previous 12 months (p < .001; OR 6.14;
95 % CI 5.77-6.53), have a primary physician (p < .001; OR 14.32; 95 % CI 13.49
15.20), or have seen a dentist (p < .001; OR 3.93; 95 % CI 3.70-4.16), and were
more likely to have a reported unmet medical need (p < .001; OR 2.60; 95 % CI
2.19-3.07). Additionally, compared to children with private insurance, those
children with public insurance were less likely to have had a check-up (p < .001;
OR 1.73; 95 % CI 1.59-1.89), have a primary care provider (p < .001; OR 3.87; 95
% CI 3.55-4.21), and were more likely to have unmet medical needs (p < .001; OR
2.27; 95 % CI 1.83-2.81). For children in early development-a deeply critical
period-insurance status and type are predictors of important access to healthcare
variables.
PMID- 24352628
TI - Anion permeation in calcium-activated chloride channels formed by TMEM16A from
Xenopus tropicalis.
AB - Calcium-activated chloride channels (CaCC) formed by anoctamin1/TMEM16A subunits
are ubiquitously expressed, and these channels are known to prevent polyspermy in
amphibian oocytes. Here, we describe a TMEM16A clone isolated from Xenopus
tropicalis oocytes (xtTMEM16A) and how the anion permeation properties are
modified in single-site mutants of the ion pore. The anion permeability sequence
was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate (relative permeabilities
5.6:3.0:2.1:1:0.2, respectively). Dose-response curves indicated that the voltage
dependent half-maximal concentration for Ca(2+) activation (K d of the Hill
equation at +100 mV) was 120 nM in normal external Cl(-), whereas it was
displaced leftward to 75 nM Ca(2+), when I(-) replaced Cl(-). The I(-):Cl(-) mole
fraction (MF) of the external solution was varied in order to gain insight into
the permeation mechanism of the pore. No anomaly in MF behavior was observed for
conductance, but it was observed for current reversal potential, which deviated
from the prediction of the Goldman-Hodgkin-Katz equation. Mutations of positively
charged amino acids in the pore, R646 and R761, to glutamate resulted in
reduction of the relative permeability to I(-). Data from the wild type and
mutants could be well fitted by a three-barrier, two-site permeation model. This
suggests a multi-ion pore with at least two binding sites for anions, with R646
mole fraction closer to the extracellular membrane surface--being important for
the stability of both sites--and R761--located deeper within the membrane--mainly
affecting the innermost binding site. Considerations of xtTMEM16A putative pore
region topology are discussed in the light of two alternative topological models
of the protein.
PMID- 24352631
TI - Amniotic membrane properties and current practice of amniotic membrane use in
ophthalmology in Slovenia.
AB - Amniotic membrane (AM) is the innermost, multilayered part of the placenta. When
harvested, processed and stored properly, its properties, stemming from AM
biological composition, make it a useful tissue for ophthalmic surgery. AM was
shown to have several beneficial effects: it promotes epithelization, has
antimicrobial effects, decreases inflammation, fibrosis and neovascularization.
Many case reports and case series as well as practical experience (e.g.
reconstruction of conjunctival and corneal defects, treatment of corneal ulcers)
demonstrated the beneficial effect of AM for different ophthalmological
indications. The combination of the above mentioned beneficial effects and
reasonable mechanical properties are also the reason why AM is used as a
substrate for ex vivo expansion of epithelial progenitor cells. Recently, amnion
derived cells, which also have stem cell characteristics, have been proposed as
potential contributors to cell-based treatment of ocular surface disease.
However, the use of AM remains one of the least standardized methods in
ophthalmic surgery. In this review, the various properties of AM and its current
clinical use in ophthalmology in Slovenia are discussed.
PMID- 24352630
TI - A novel calmodulin site in the Cav1.2 N-terminus regulates calcium-dependent
inactivation.
AB - The L-type voltage-gated calcium channel Cav1.2 is important for excitation
contraction coupling in the heart, as well as CREB-mediated transcription in the
brain. The ubiquitous calcium-binding protein calmodulin (CaM) is known to
modulate calcium-dependent inactivation (CDI) of these channels, thus limiting
the amount of calcium entering via Cav1.2 during prolonged or repetitive membrane
depolarizations. The proximal N-terminus of Cav1.2 contains a CaM-binding site at
residue W52 that is critical for a type of CDI that is mediated by the N-terminal
lobe of CaM. Here, we identify a second CaM interaction site in the Cav1.2 N
terminus downstream of the W52 site that is formed by residue C106. We show by
site-directed mutagenesis coupled with electrophysiological measurements that
this region of the channel functionally partakes in N-lobe CDI, likely by acting
as a gating transduction motif. Thus, our data indicate that calcium regulation
of Cav1.2 channels is more complex than previously thought, and involves more
than one region within the channel's N-terminal domain.
PMID- 24352629
TI - The SLC34 family of sodium-dependent phosphate transporters.
AB - The SLC34 family of sodium-driven phosphate cotransporters comprises three
members: NaPi-IIa (SLC34A1), NaPi-IIb (SLC34A2), and NaPi-IIc (SLC34A3). These
transporters mediate the translocation of divalent inorganic phosphate (HPO4 (2
)) together with two (NaPi-IIc) or three sodium ions (NaPi-IIa and NaPi-IIb),
respectively. Consequently, phosphate transport by NaPi-IIa and NaPi-IIb is
electrogenic. NaPi-IIa and NaPi-IIc are predominantly expressed in the brush
border membrane of the proximal tubule, whereas NaPi-IIb is found in many more
organs including the small intestine, lung, liver, and testis. The abundance and
activity of these transporters are mostly regulated by changes in their
expression at the cell surface and are determined by interactions with proteins
involved in scaffolding, trafficking, or intracellular signaling. All three
transporters are highly regulated by factors including dietary phosphate status,
hormones like parathyroid hormone, 1,25-OH2 vitamin D3 or FGF23, electrolyte, and
acid-base status. The physiological relevance of the three members of the SLC34
family is underlined by rare Mendelian disorders causing phosphaturia,
hypophosphatemia, or ectopic organ calcifications.
PMID- 24352632
TI - Fetal safety of erythromycin. An update of Swedish data.
AB - PURPOSE: In previous studies from the Swedish Medical Birth Register, a possible
association between erythromycin therapy and an increased risk for cardiovascular
defects was found. Other studies using different methodology have not verified
this observation. The finding resulted in a warning for the use of erythromycin
in early pregnancy, followed by a marked decline in such use. The present study
was conducted to follow up on the previous observations and to find
methodological explanations for the variation in results in these different
published studies. METHODS: Data on Swedish women who gave birth during the
period 1996-2011 were studied using the drug information in the Medical Birth
Registry, obtained from midwife interviews conducted toward the end of the first
trimester. Data on the presence of congenital malformations were ascertained from
national health registers. Odds ratios were then determined using the Mantel
Haenszel methodology. RESULTS: A persistent association was seen between
erythromycin use and the occurrence of cardiovascular defects, with a risk
estimate of 1.70 (95 % confidence interval (CI): 1.26-2.39), of similar strength
during the first and last 8 years of observation. We discussed the contradictory
findings of the other published studies and pointed out possible methodological
problems that may explain the absence of an effect in studies based on
prescription registers. CONCLUSIONS: Our study verified an association between
early pregnancy erythromycin use and infant cardiovascular defects; most defects
were mild. The cause of this association is unclear.
PMID- 24352634
TI - Nanoparticle dispersion in polymer nanocomposites by spin-diffusion-averaged
paramagnetic enhanced NMR relaxometry.
AB - We developed an analytical relationship between nuclear magnetic relaxation and
interparticle spacings in polymer nanocomposites filled with paramagnetic
impurity-containing clay nanoparticles. Using (1)H NMR relaxometry, clay
nanoparticle dispersion was quantified and agrees with interparticle spacing
distributions determined from statistical analysis of TEM images. Some
information on the overall quality of clay dispersion is revealed. This work
offers a new approach and new insights into nanoparticle dispersion in polymer
nanocomposites.
PMID- 24352633
TI - Pharmacokinetic changes after placement of a transjugular intrahepatic
portosystemic shunt.
PMID- 24352636
TI - Training clinical skills in Pairs.
PMID- 24352635
TI - Disease and treatment perceptions among Asian Americans diagnosed with chronic
hepatitis B infection.
AB - BACKGROUND: In the US, over 1 million Asian Americans are estimated to be living
with chronic hepatitis B (CHB). Research has shown low awareness of CHB and
different attitudes towards its treatment among the diverse ethnicities of Asian
Americans. OBJECTIVE: This study aimed to understand the perceptions and
attitudes of CHB treatment among Asian Americans diagnosed with CHB who were
either treatment-naive or being treated for CHB with oral antivirals, and to
understand the relative importance of different clinical and economic attributes
of oral antivirals that affect CHB treatment decisions and choices. DESIGN: Face
to-face structured survey administered to participants at central research
facilities by interviewers of each participating ethnicity. PARTICIPANTS: CHB
patients from Chinese, Korean, and Vietnamese communities of New York
metropolitan, San Francisco/Bay, and Los Angeles/Orange County areas. MAIN
MEASURES: A 'conjoint' exercise (discrete choice model) assessed the relative
impact of treatment attributes on treatment choice. Implicit "trade-off"
decisions made by respondents were estimated using a hierarchical Bayesian model.
KEY RESULTS: Among 252 participants, 36 % were Chinese, 34 % Vietnamese, and 31 %
Korean; 56 % were treatment-naive and 44 % were being treated with an oral
antiviral for CHB. The majority (88 %) believed that, if left untreated, CHB can
lead to serious liver damage; 72 % believed there are effective prescription
medications to treat CHB; and 39 % showed reluctance to be on long-term therapy
for CHB because of concerns over side effects. Long-term risk of kidney damage
was given the highest relative importance (38 %) when choosing CHB treatment,
followed by medication cost (23.4 %), long-term risk of bone thinning (18 %),
long-term efficacy (9 %), time on US market (6.8 %), and number of patients
treated globally (4.9 %). Results were consistent across ethnicities.
CONCLUSIONS: Patients need access to improved education regarding CHB disease
progression, its management, disease outcomes, and the importance of long-term
treatment of the disease.
PMID- 24352638
TI - A novel technique for modified onlay incisional hernia repair with mesh
incorporation into the fascial defect: a method for addressing suture line
failure.
AB - PURPOSE: Biological mechanisms such as abnormal wound healing and impaired scar
formation are important aetiological factors in the development of abdominal wall
hernias. Standard onlay repair often involves suture closure of the fascial
defect with placement of the mesh over this closed defect. This has the
disadvantage that suture line failure may occur early in the healing process and
predispose to recurrence. Our technique aims to overcome this by incorporating
the mesh into the fascial closure. The aim of this retrospective study was to
audit recurrence rate and surgical complications relating to this modified
repair. METHODS: This study included all patients undergoing incisional hernia
repair over a 5-year period under a single consultant. An initial stitch was
taken through the Ultrapro(TM) mesh and fascia on one side of the defect followed
by the fascia and mesh on the other side. By repeating this process with a
continuous suture, the mesh was incorporated into the fascial defect closure.
Telephone survey was performed, and where there was suspicion of a recurrence
patients were brought back to the outpatient clinic. RESULTS: The study included
72 patients with a median follow-up of 29 months. There was a 7 % recurrence rate
and a 10 % minor complication rate, with no patient requiring readmission or mesh
removal. In 70 % of patients the procedure was performed as a day case and 90 %
were satisfied with the repair. CONCLUSIONS: This is a promising new technique
that aims to address suture line failure and the significant recurrence rate that
occurs with incisional hernia repair.
PMID- 24352639
TI - The injurious effects of hyperinsulinism on blood vessels.
AB - Insulin resistance (IR) is a common feature of hypertension, Type II diabetes,
coronary heart disease, Syndrome X, and other vascular diseases. It refers to a
state in which a certain concentration of insulin produces less biologic effect
than expected in human body. When IR develops, the response of human body to
insulin decreases accordingly, thus inducing the compensatory hyper-secretion of
insulin and consequently hyperinsulinism. Many clinical and epidemiologic studies
have demonstrated that IR and iatrogenic hyperinsulinism induced consequently
play an essential role in the pathogenesis of hypertension and atherosclerotic
cardiovascular diseases. Therefore, more and more attention should be paid to the
mechanism of IR in order to explore more therapeutic basis and prospective for
the treatment of atherosclerosis and other cardiovascular diseases. In this
review, we provided a general overview on the known molecular mechanisms of IR
and summarized the recent findings on the injurious effects of hyperinsulinism in
vitro and in vivo, which might be important for researchers and clinicians to
better understand the etiology and clinical significance of IR.
PMID- 24352640
TI - Duty of candour and the definition of moderate harm for radiation overexposure
and exposures much greater than intended in diagnostic radiology.
PMID- 24352641
TI - Managing breast cancers with low estrogen receptor and HER2 by drugging both.
AB - Low estrogen receptor (ER) levels in breast tumors are associated with poorer
response to antiestrogen therapy. Finn and colleagues identify low ER levels as a
biomarker predicting benefit from the addition of the EGFR/HER2 dual inhibitor
lapatinib to an antiestrogen treatment regimen in patients with metastatic
ER(+)/HER2(-) breast cancer.
PMID- 24352642
TI - Genetic profiling to determine risk of relapse-free survival in high-risk
localized prostate cancer.
AB - PURPOSE: The characterization of actionable mutations in human tumors is a
prerequisite for the development of individualized, targeted therapy. We examined
the prevalence of potentially therapeutically actionable mutations in patients
with high-risk clinically localized prostate cancer. EXPERIMENTAL DESIGN: Forty
eight samples of formalin-fixed paraffin-embedded prostatectomy tissue from a
neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected
tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass
spectroscopy-based sequencing. In addition, PTEN loss and erythroblast
transformation-specific-related gene (ERC) translocations were examined using
immunohistochemistry (IHC) in associated tissue microarrays. Association with
relapse during 5 years of follow-up was examined in exploratory analyses of the
potential clinical relevance of the genetic alterations. RESULTS: Of the 40
tumors evaluable for mutations, 10% had point mutations in potentially actionable
cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had
ERG rearrangement. Individual mutations were not frequent enough to determine
associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the
16 patients who had PTEN loss had a significantly shorter median relapse-free
survival, 19 versus 106 months (P = 0.01). CONCLUSIONS: This study confirms that
point mutations in the most common cancer regulatory genes in prostate cancer are
rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. Although
point mutations alone did not have a statistically significant association with
relapse, PTEN loss was associated with an increased relapse in high-risk prostate
cancer treated with chemotherapy followed by surgery.
PMID- 24352643
TI - EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral
glioma and generates host immunity against tumor-antigen loss.
AB - PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising
immune therapy that has been shown to successfully treat cancers in mice and
humans. However, CARs targeting antigens expressed in both tumors and normal
tissues have led to significant toxicity. Preclinical studies have been limited
by the use of xenograft models that do not adequately recapitulate the immune
system of a clinically relevant host. A constitutively activated mutant of the
naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically
identical in both human and mouse glioma, but is also completely absent from any
normal tissues. EXPERIMENTAL DESIGN: We developed a third-generation, EGFRvIII
specific murine CAR (mCAR), and performed tests to determine its efficacy in a
fully immunocompetent mouse model of malignant glioma. RESULTS: At elevated
doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain
tumors. In addition, antitumor efficacy was found to be dependent on
lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble
peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro
and in vivo, and may offer a novel strategy to enhance the safety profile for CAR
based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge
with EGFRvIII(NEG) tumors, suggesting generation of host immunity against
additional tumor antigens. CONCLUSION: All together, these data support that
third-generation, EGFRvIII-specific mCARs are effective against gliomas in the
brain and highlight the importance of syngeneic, immunocompetent models in the
preclinical evaluation of tumor immunotherapies.
PMID- 24352644
TI - Cellular uptake of imatinib into leukemic cells is independent of human organic
cation transporter 1 (OCT1).
AB - PURPOSE: In addition to mutated BCR-ABL1 kinase, the organic cation transporter 1
(OCT1, encoded by SLC22A1) has been considered to contribute to imatinib
resistance in patients with chronic myeloid leukemia (CML). As data are
conflicting as to whether OCT1 transports imatinib and may serve as a clinical
biomarker, we used a combination of different approaches including animal
experiments to elucidate comprehensively the impact of OCT1 on cellular imatinib
uptake. EXPERIMENTAL DESIGN: Transport of imatinib was studied using OCT1
expressing Xenopus oocytes, mammalian cell lines (HEK293, MDCK, V79) stably
expressing OCT1, human leukemic cells, and Oct1-knockout mice. OCT1 mRNA and
protein expression were analyzed in leukemic cells from patients with imatinib
naive CML as well as in cell lines. RESULTS: Transport and inhibition studies
showed that overexpression of functional OCT1 protein in Xenopus oocytes or
mammalian cell lines did not lead to an increased cellular accumulation of
imatinib. The CML cell lines (K562, Meg-01, LAMA84) and leukemic cells from
patients expressed neither OCT1 mRNA nor protein as demonstrated by
immunoblotting and immunofluorescence microscopy, yet they showed a considerable
imatinib uptake. Oct1 deficiency in mice had no influence on plasma and hepatic
imatinib concentrations. CONCLUSIONS: These data clearly demonstrate that
cellular uptake of imatinib is independent of OCT1, and therefore OCT1 is
apparently not a valid biomarker for imatinib resistance.
PMID- 24352645
TI - Integrated microRNA network analyses identify a poor-prognosis subtype of gastric
cancer characterized by the miR-200 family.
AB - PURPOSE: Our aim was to investigate whether microRNAs can predict the clinical
outcome of patients with gastric cancer. We used integrated analysis of microRNA
and mRNA expression profiles to identify gastric cancer microRNA subtypes and
their underlying regulatory scenarios. EXPERIMENTAL DESIGN: MicroRNA-based
gastric cancer subtypes were identified by consensus clustering analysis of
microRNA profiles of 90 gastric cancer tissues. Activated pathways in the
subtypes were identified by gene expression profiles. Further integrated analysis
was conducted to model a microRNA regulatory network for each subtype. RNA and
protein expression were analyzed by RT-PCR and tissue microarray, respectively,
in a cohort of 385 gastric cancer cases (including the 90 cases for profiling) to
validate the key microRNAs and targets in the network. Both in vitro and in vivo
experiments were carried out to further validate the findings. RESULTS: MicroRNA
profiles of 90 gastric cancer cases identified two microRNA subtypes
significantly associated with survival. The poor-prognosis gastric cancer
microRNA subtype was characterized by overexpression of epithelial-to-mesenchymal
transition (EMT) markers. This gastric cancer "mesenchymal subtype" was further
validated in a patient cohort comprising 385 cases. Integrated analysis
identified a key microRNA regulatory network likely driving the gastric cancer
mesenchymal subtype. Three of the microRNAs (miR-200c, miR-200b, and miR-125b)
targeting the most genes in the network were significantly associated with
survival. Functional experiments demonstrated that miR-200b suppressed ZEB1,
augmented E-cadherin, inhibited cell migration, and suppressed tumor growth in a
mouse model. CONCLUSIONS: We have uncovered a key microRNA regulatory network
that defines the mesenchymal gastric cancer subtype significantly associated with
poor overall survival in gastric cancer.
PMID- 24352647
TI - Inhibition of protein kinase C/Twist1 signaling augments anticancer effects of
androgen deprivation and enzalutamide in prostate cancer.
AB - PURPOSE: The progression of prostate cancer to metastatic and castration
resistant disease represents a critical step. We previously showed that the
transcription factor Twist1, which promotes epithelial-mesenchymal transition,
was involved in castration-resistant progression. Similarly, protein kinase C
(PKC) has been implicated in both metastatic progression and castration
resistance in prostate cancer. EXPERIMENTAL DESIGN: In this study, we aimed to
elucidate the role of PKC/Twist1 signaling in castration resistance, and to apply
this information to the development of a novel therapeutic concept using PKC
inhibitor Ro31-8220 against prostate cancer using various prostate cancer cell
lines. RESULTS: Androgen deprivation and the next-generation antiandrogen
enzalutamide induced PKC activation and Twist1 expression, which were reversed by
the PKC inhibitor Ro31-8220. Ro31-8220 suppressed cell proliferation in androgen
dependent prostate cancer LNCaP cells, which was augmented by its combination
with androgen deprivation or enzalutamide. The favorable anticancer effects of
the combination of Ro31-8220 and enzalutamide were also observed in castration
resistant C4-2 and 22Rv1 cells. Furthermore, PKC phosphorylation was elevated in
castration-resistant and enzalutamide-resistant cells compared with their
parental cells, leading to persistent sensitivity to Ro-31-8220 in castration-
and enzalutamide-resistant cells. CONCLUSIONS: Taken together, these findings
indicate that PKC/Twist1 signaling contributes to castration resistance as well
as enzalutamide resistance in prostate cancer, and suggest that therapeutics
targeting PKC/Twist1 signaling, such as PKC inhibitors, represent a promising
novel therapeutic strategy for prostate cancer, especially castration-resistant
prostate cancer, when combined with enzalutamide.
PMID- 24352646
TI - Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1
overexpression and mantle cell lymphoma: from molecular profiling to flow
cytometry.
AB - PURPOSE: According to current diagnostic criteria, mantle cell lymphoma (MCL)
encompasses the usual, aggressive variants and rare, nonnodal cases with
monoclonal asymptomatic lymphocytosis, cyclin D1-positive (MALD1). We aimed to
understand the biology behind this clinical heterogeneity and to identify markers
for adequate identification of MALD1 cases. EXPERIMENTAL DESIGN: We compared 17
typical MCL cases with a homogeneous group of 13 untreated MALD1 cases (median
follow-up, 71 months). We conducted gene expression profiling with functional
analysis in five MCL and five MALD1. Results were validated in 12 MCL and 8 MALD1
additional cases by quantitative reverse transcription polymerase chain reaction
(qRT-PCR) and in 24 MCL and 13 MALD1 cases by flow cytometry. Classification and
regression trees strategy was used to generate an algorithm based on CD38 and
CD200 expression by flow cytometry. RESULTS: We found 171 differentially
expressed genes with enrichment of neoplastic behavior and cell proliferation
signatures in MCL. Conversely, MALD1 was enriched in gene sets related to immune
activation and inflammatory responses. CD38 and CD200 were differentially
expressed between MCL and MALD1 and confirmed by flow cytometry (median CD38, 89%
vs. 14%; median CD200, 0% vs. 24%, respectively). Assessment of both proteins
allowed classifying 85% (11 of 13) of MALD1 cases whereas 15% remained
unclassified. SOX11 expression by qRT-PCR was significantly different between MCL
and MALD1 groups but did not improve the classification. CONCLUSION: We show for
the first time that MALD1, in contrast to MCL, is characterized by immune
activation and driven by inflammatory cues. Assessment of CD38/CD200 by flow
cytometry is useful to distinguish most cases of MALD1 from MCL in the clinical
setting. MALD1 should be identified and segregated from the current MCL category
to avoid overdiagnosis and unnecessary treatment.
PMID- 24352648
TI - Molecular pathways: response and resistance to BRAF and MEK inhibitors in
BRAF(V600E) tumors.
AB - The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase)
pathway plays a central role in driving proliferation, survival, and metastasis
signals in tumor cells, and the prevalence of oncogenic mutations in RAS and BRAF
and upstream nodes makes this pathway the focus of significant oncology drug
development efforts. This focus has been justified by the recent success of BRAF
and MEK inhibitors in prolonging the lives of patients with BRAF(V600E/K)-mutant
melanoma. Although it is disappointing that cures are relatively rare, this
should not detract from the value of these agents to patients with cancer and the
opportunity they provide in allowing us to gain a deeper understanding of drug
response and resistance. These insights have already provided the basis for the
evaluation of alternative dosing regimens and combination therapies in patients
with melanoma.
PMID- 24352649
TI - Self-ignited high temperature synthesis and enhanced super-exchange interactions
of Ho(3+)-Mn(2+)-Fe(3+)-O(2-) ferromagnetic nanoparticles.
AB - The present work is focused on the effect of Fe(3+) replacement by rare earth
Ho(3+) ions and their influence on the properties of MnFe2O4 ferrite. The Ho(3+)
substituted MnFe2O4 ferrite samples with chemical formula MnHoxFe2-xO4 were
synthesized where substitution concentration of Ho(3+) was 0.0, 0.05, 0.1 and
0.15. The samples were synthesized by the self-ignited sol-gel method using the
nitrates of the respective elements. Powder X-ray diffraction, transmission
electron microscopy, infrared spectroscopy, vibrating sample magnetometer (VSM)
and electrical measurements were employed to characterize the structural,
magnetic and electrical properties of these ferrite nanoparticles. The cations
distribution between the tetrahedral (A-site) and octahedral sites (B-site) has
been estimated by XRD analysis. It is found that substitution of Ho(3+) ions
favorably influenced the magnetic and electrical properties. Magnetic
measurements were carried out at 77 and 300 K. Saturation magnetization and
coercivity increased from 54.57 to 71.6 emu g(-1) and 172 to 766 Oe,
respectively, with increasing the Ho(3+) substitution. The change in magnetic
properties may be explained with the increase of A-O-B (FeA(3+)-O(2-)-HoB(3+))
super exchange interactions and the anisotropy constant. The electrical
properties show that the pure sample has lower resistivity with respect to any
Ho(3+) doped one. The conduction mechanism is used to interpret electrical
measurements. Results of the presently investigated samples with enhanced
saturation magnetization, coercivity and remanence ratio indicate that the Ho(3+)
doped MnFe2O4 nanoparticles can be a useful candidate for the application in high
density recording media.
PMID- 24352650
TI - Exclusive breastfeeding among Canadian Inuit: results from the Nunavut Inuit
Child Health Survey.
AB - BACKGROUND: Very little population-based research has been conducted around the
exclusive breastfeeding practices of Inuit Canadians. OBJECTIVES: This research
aims to assess the distribution of exclusive breastfeeding among Inuit Canadians
and to identify factors associated with exclusive breastfeeding as recommended.
METHODS: We use data from 188 infant-mother dyads who completed the Nunavut Inuit
Child Health Survey, a cross-sectional, population-based survey of Inuit children
aged 3 to 5 years. A series of multinomial logistic regression models were run to
identify factors associated with 4 exclusive breastfeeding durations (<= 1 month,
> 1-< 5.5 months, 5.5-6.5 months, and > 6.5 months). RESULTS: Of infants, 23%
were exclusively breastfed as recommended (ie, between 5.5 and 6.5 months; 95%
CI, 16.2-29.3). Many infants (61%) were exclusively breastfed for less than 5.5
months and 16% (95% CI, 10.9-22.0) were exclusively breastfed for more than 6.5
months. Families receiving income support were less likely to discontinue
exclusive breastfeeding before 5.5 months (pOR1- < 5.5 months = 0.34; 95% CI,
0.13, 0.85) relative to those not receiving income support, in adjusted models.
No other measured factors were significantly related to exclusive breastfeeding
duration. CONCLUSIONS: The majority of Inuit Canadian infants receive suboptimal
exclusive breastfeeding. National, provincial, and community-specific
interventions to protect, promote, and support exclusive breastfeeding should
emphasize not only the benefits of exclusively breastfeeding to 6 months but also
the importance of timely introduction of complementary foods into the infant's
diet.
PMID- 24352651
TI - Body composition changes in the first 6 months of life according to method of
feeding.
AB - BACKGROUND: Early feeding choices may affect long-term health outcomes.
Therefore, understanding body composition changes in healthy breastfed infants
has become an important research focus. OBJECTIVES: The aims of this review were
to investigate the body composition changes that occur during weight loss in
breastfed term newborns and to examine body composition differences between
exclusively/predominantly breastfed and exclusively formula-fed infants in the
first 6 months of life. METHODS: We performed a review of the existing literature
using PubMed. We searched for studies published in English since January 1, 2000,
that involved human infants ranging in age from birth to 6 months. We used the
following MEDLINE Medical Subject Headings: ((breastfeeding) OR (infant formula))
AND ((body composition) OR (bioelectrical impedance) OR (absorptiometry, photon)
OR (total body potassium) OR (isotope dilution) OR (air-displacement
plethysmography)). Our search yielded 6 studies. RESULTS: Two studies reported
that newborn weight loss was due to a reduction in the quantity of both fat mass
and fat-free mass. Three out of 4 articles that evaluated body composition
changes according to method of feeding reported no differences in body
composition between exclusively/predominantly breastfed and exclusively formula
fed infants in the first 4.5 months of life. One study reported that exclusively
breastfed infants at 3 months of age and exclusively breastfed boys at 6 months
of age had higher fat mass contents compared to exclusively formula-fed infants.
CONCLUSION: Because of the limited number of studies available, larger studies
are needed to clarify the differences in body composition between
exclusively/predominantly breastfed and exclusively formula-fed infants.
PMID- 24352653
TI - Is minimally invasive colon resection better than traditional approaches?: First
comprehensive national examination with propensity score matching.
AB - IMPORTANCE: Minimally invasive colectomies are increasingly popular options for
colon resection. OBJECTIVE: To compare the perioperative outcomes and costs of
robot-assisted colectomy (RC), laparoscopic colectomy (LC), and open colectomy
(OC). DESIGN, SETTING, AND PARTICIPANTS: The US Nationwide Inpatient Sample
database was used to examine outcomes and costs before and after propensity score
matching across the 3 surgical approaches. This study involved a sample of US
hospital discharges from 2008 to 2010 and all patients 21 years of age or older
who underwent elective colectomy. MAIN OUTCOMES AND MEASURES In-hospital
mortality, complications, ostomy rates, conversion to open procedure, length of
stay, discharge disposition, and cost. RESULTS: Of the 244129 colectomies
performed during the study period, 126284 (51.7%) were OCs, 116261 (47.6%) were
LCs, and 1584 (0.6%) were RCs. In comparison with OC, LC was associated with a
lower mortality rate (0.4% vs 2.0%), lower complication rate (19.8% vs 33.2%),
lower ostomy rate (3.5 vs 13.0%), shorter median length of stay (4 vs 6 days), a
higher routine discharge rate (86.1% vs 68.4%), and lower overall cost than OC
($11742 vs $13666) (all P<.05). Comparison between RC and LC showed no
significant differences with respect to in-hospital mortality (0.0% vs 0.7%),
complication rates (14.7% vs 18.5%), ostomy rates (3.0% vs 5.1%), conversions to
open procedure (5.7% vs 9.9%), and routine discharge rates (88.7% vs 88.5%) (all
P>.05). However, RC incurred a higher overall hospitalization cost than LC
($14847 vs $11966, P<.001). CONCLUSIONS AND RELEVANCE: In this nationwide
comparison of minimally invasive approaches for colon resection, LC demonstrated
favorable clinical outcomes and lower cost than OC. Robot-assisted colectomy was
equivalent in most clinical outcomes to LC but incurred a higher cost.
PMID- 24352654
TI - The health reform monitoring survey: addressing data gaps to provide timely
insights into the affordable care act.
AB - The Health Reform Monitoring Survey (HRMS) was launched in 2013 as a mechanism to
obtain timely information on the Affordable Care Act (ACA) during the period
before federal government survey data for 2013 and 2014 will be available. Based
on a nationally representative, probability-based Internet panel, the HRMS
provides quarterly data for approximately 7,400 nonelderly adults and 2,400
children on insurance coverage, access to health care, and health care
affordability, along with special topics of relevance to current policy and
program issues in each quarter. For example, HRMS data from summer 2013 show that
more than 60 percent of those targeted by the health insurance exchanges struggle
with understanding key health insurance concepts. This raises concerns about some
people's ability to evaluate trade-offs when choosing health insurance plans.
Assisting people as they attempt to enroll in health coverage will require
targeted education efforts and staff to support those with low health insurance
literacy.
PMID- 24352655
TI - Combined effects of ankylosing spondylitis-associated ERAP1 polymorphisms outside
the catalytic and peptide-binding sites on the processing of natural HLA-B27
ligands.
AB - ERAP1 polymorphism involving residues 528 and 575/725 is associated with
ankylosing spondylitis among HLA-B27-positive individuals. We used four
recombinant variants to address the combined effects of the K528R and D575N
polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a
fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys
528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or
Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575,
but the difference depended on residue 528. The same hierarchy was observed with
synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent.
Sometimes the epitope yields were variant-specific at all times. For other
peptides, concomitant generation and destruction led to similar epitope amounts
with all the variants at long, but not at short, digestion times. The
generation/destruction balance of two related HLA-B27 ligands was analyzed in
vitro and in live cells. Their relative yields at long digestion times were
comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a
major determinant of the abundance of these peptides in vivo. The hydrolysis of
fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide,
respectively, was increasingly inhibited as a function of ERAP1 activity,
indicating that residues 528 and 575 affect substrate inhibition of ERAP1
trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms
on multiple HLA-B27 ligands, and their potential to alter the immunological and
pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the
epistatic association of both molecules in ankylosing spondylitis.
PMID- 24352656
TI - Rho-GTPase-activating protein interacting with Cdc-42-interacting protein 4
homolog 2 (Rich2): a new Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase
activating protein that controls dendritic spine morphogenesis.
AB - Development of dendritic spines is important for synaptic function, and
alteration in spine morphogenesis is often associated with mental disorders.
Rich2 was an uncharacterized Rho-GAP protein. Here we searched for a role of this
protein in spine morphogenesis. We found that it is enriched in dendritic spines
of cultured hippocampal pyramidal neurons during early stages of development.
Rich2 specifically stimulated the Rac1 GTPase in these neurons. Inhibition of
Rac1 by EHT 1864 increased the size and decreased the density of dendritic
spines. Similarly, Rich2 overexpression increased the size and decreased the
density of dendritic spines, whereas knock-down of the protein by specific si-RNA
decreased both size and density of spines. The morphological changes were
reflected by the increased amplitude and decreased frequency of miniature EPSCs
induced by Rich2 overexpression, while si-RNA treatment decreased both amplitude
and frequency of these events. Finally, treatment of neurons with EHT 1864
rescued the phenotype induced by Rich2 knock-down. These results suggested that
Rich2 controls dendritic spine morphogenesis and function via inhibition of Rac1.
PMID- 24352657
TI - scyllo-Inositol promotes robust mutant Huntingtin protein degradation.
AB - Huntington disease is characterized by neuronal aggregates and inclusions
containing polyglutamine-expanded huntingtin protein and peptide fragments (polyQ
Htt). We have used an established cell-based assay employing a PC12 cell line
overexpressing truncated exon 1 of Htt with a 103-residue polyQ expansion that
yields polyQ-Htt aggregates to investigate the fate of polyQ-Htt-drug complexes.
scyllo-Inositol is an endogenous inositol stereoisomer known to inhibit
accumulation and toxicity of the amyloid-beta peptide and alpha-synuclein. In
light of these properties, we investigated the effect of scyllo-inositol on polyQ
Htt accumulation. We show that scyllo-inositol lowered the number of visible
polyQ-Htt aggregates and robustly decreased polyQ-Htt protein abundance without
concomitant cellular toxicity. We found that scyllo-inositol-induced polyQ-Htt
reduction was by rescue of degradation pathways mediated by the lysosome and by
the proteasome but not autophagosomes. The rescue of degradation pathways was not
a direct result of scyllo-inositol on the lysosome or proteasome but due to
scyllo-inositol-induced reduction in mutant polyQ-Htt protein levels.
PMID- 24352658
TI - Pharmacologic stimulation of cytochrome P450 46A1 and cerebral cholesterol
turnover in mice.
AB - Cytochrome P450 46A1 (CYP46A1) is a brain-specific cholesterol 24-hydroxylase
responsible for the majority of cholesterol elimination from the brain.
Genetically increased CYP46A1 expression in mice leads to improved cognition and
decreases manifestations of Alzheimer disease. We found that four pharmaceuticals
(efavirenz (EFV), acetaminophen, mirtazapine, and galantamine) prescribed for
indications unrelated to cholesterol maintenance increased CYP46A1 activity in
vitro. We then evaluated the anti-HIV medication EFV for the mode of interaction
with CYP46A1 and the effect on mice. We propose a model for CYP46A1 activation by
EFV and show that EFV enhanced CYP46A1 activity and cerebral cholesterol turnover
in animals with no effect on the levels of brain cholesterol. The doses of EFV
administered to mice and required for the stimulation of their cerebral
cholesterol turnover are a hundred times lower than those prescribed to HIV
patients. At such small doses, EFV may be devoid of adverse effects elicited by
high drug concentrations. CYP46A1 could be a novel therapeutic target and a tool
to further investigate the physiological and medical significance of cerebral
cholesterol turnover.
PMID- 24352659
TI - Host SAMHD1 protein promotes HIV-1 recombination in macrophages.
AB - Template switching can occur during the reverse transcription of HIV-1.
Deoxynucleotide triphosphate (dNTP) concentrations have been biochemically shown
to impact HIV-1 reverse transcriptase (RT)-mediated strand transfer. Lowering the
dNTP concentrations promotes RT pausing and RNA template degradation by RNase H
activity of the RT, subsequently leading to strand transfer. Terminally
differentiated/nondividing macrophages, which serve as a key HIV-1 reservoir,
contain extremely low dNTP concentrations (20-50 nm), which results from the
cellular dNTP hydrolyzing sterile alpha motif and histidine aspartic domain
containing protein 1 (SAMHD1) protein, when compared with activated CD4(+) T
cells (2-5 MUm). In this study, we first observed that HIV-1 template switching
efficiency was nearly doubled in human primary macrophages when compared with
activated CD4(+) T cells. Second, SAMHD1 degradation by viral protein X (Vpx),
which elevates cellular dNTP concentrations, decreased HIV-1 template switching
efficiency in macrophages to the levels comparable with CD4(+) T cells. Third,
differentiated SAMHD1 shRNA THP-1 cells have a 2-fold increase in HIV-1 template
switching efficiency. Fourth, SAMHD1 degradation by Vpx did not alter HIV-1
template switching efficiency in activated CD4(+) T cells. Finally, the HIV-1
V148I RT mutant that is defective in dNTP binding and has DNA synthesis delay
promoted RT stand transfer when compared with wild type RT, particularly at low
dNTP concentrations. Here, we report that SAMHD1 regulation of the dNTP
concentrations influences HIV-1 template switching efficiency, particularly in
macrophages.
PMID- 24352660
TI - Control of vascular permeability by atrial natriuretic peptide via a GEF-H1
dependent mechanism.
AB - Microtubule (MT) dynamics is involved in a variety of cell functions, including
control of the endothelial cell (EC) barrier. Release of Rho-specific nucleotide
exchange factor GEF-H1 from microtubules activates the Rho pathway of EC
permeability. In turn, pathologic vascular leak can be prevented by treatment
with atrial natriuretic peptide (ANP). This study investigated a novel mechanism
of vascular barrier protection by ANP via modulation of GEF-H1 function. In
pulmonary ECs, ANP suppressed thrombin-induced disassembly of peripheral MT and
attenuated Rho signaling and cell retraction. ANP effects were mediated by the
Rac1 GTPase effector PAK1. Activation of Rac1-PAK1 promoted PAK1 interaction with
the Rho activator GEF-H1, inducing phosphorylation of total and MT-bound GEF-H1
and leading to attenuation of Rho-dependent actin remodeling. In vivo, ANP
attenuated lung injury caused by excessive mechanical ventilation and TRAP
peptide (TRAP/HTV), which was further exacerbated in ANP(-/-) mice. The
protective effects of ANP against TRAP/HTV-induced lung injury were linked to the
increased pool of stabilized MT and inactivation of Rho signaling via ANP
induced, PAK1-dependent inhibitory phosphorylation of GEF-H1. This study
demonstrates a novel protective mechanism of ANP against pathologic
hyperpermeability and suggests a novel pharmacological intervention for the
prevention of increased vascular leak via PAK1-dependent modulation of GEF-H1
activity.
PMID- 24352661
TI - gamma-Secretase processing and effects of gamma-secretase inhibitors and
modulators on long Abeta peptides in cells.
AB - Understanding how different species of Abeta are generated by gamma-secretase
cleavage has broad therapeutic implications, because shifts in gamma-secretase
processing that increase the relative production of Abetax-42/43 can initiate a
pathological cascade, resulting in Alzheimer disease. We have explored the
sequential stepwise gamma-secretase cleavage model in cells. Eighteen BRI2-Abeta
fusion protein expression constructs designed to generate peptides from Abeta1-38
to Abeta1-55 and C99 (CTFbeta) were transfected into cells, and Abeta production
was assessed. Secreted and cell-associated Abeta were detected using ELISA and
immunoprecipitation MALDI-TOF mass spectrometry. Abeta peptides from 1-38 to 1-55
were readily detected in the cells and as soluble full-length Abeta proteins in
the media. Abeta peptides longer than Abeta1-48 were efficiently cleaved by gamma
secretase and produced varying ratios of Abeta1-40:Abeta1-42. gamma-Secretase
cleavage of Abeta1-51 resulted in much higher levels of Abeta1-42 than any other
long Abeta peptides, but the processing of Abeta1-51 was heterogeneous with
significant amounts of shorter Abetas, including Abeta1-40, produced. Two PSEN1
variants altered Abeta1-42 production from Abeta1-51 but not Abeta1-49.
Unexpectedly, long Abeta peptide substrates such as Abeta1-49 showed reduced
sensitivity to inhibition by gamma-secretase inhibitors. In contrast, long Abeta
substrates showed little differential sensitivity to multiple gamma-secretase
modulators. Although these studies further support the sequential gamma-secretase
cleavage model, they confirm that in cells the initial gamma-secretase cleavage
does not precisely define subsequent product lines. These studies also raise
interesting issues about the solubility and detection of long Abeta, as well as
the use of truncated substrates for assessing relative potency of gamma-secretase
inhibitors.
PMID- 24352662
TI - Evidence for hysteretic substrate channeling in the proline dehydrogenase and
Delta1-pyrroline-5-carboxylate dehydrogenase coupled reaction of proline
utilization A (PutA).
AB - PutA (proline utilization A) is a large bifunctional flavoenzyme with proline
dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH)
domains that catalyze the oxidation of l-proline to l-glutamate in two successive
reactions. In the PRODH active site, proline undergoes a two-electron oxidation
to Delta(1)-pyrroline-5-carboxlylate, and the FAD cofactor is reduced. In the
P5CDH active site, l-glutamate-gamma-semialdehyde (the hydrolyzed form of
Delta(1)-pyrroline-5-carboxylate) undergoes a two-electron oxidation in which a
hydride is transferred to NAD(+)-producing NADH and glutamate. Here we report the
first kinetic model for the overall PRODH-P5CDH reaction of a PutA enzyme. Global
analysis of steady-state and transient kinetic data for the PRODH, P5CDH, and
coupled PRODH-P5CDH reactions was used to test various models describing the
conversion of proline to glutamate by Escherichia coli PutA. The coupled PRODH
P5CDH activity of PutA is best described by a mechanism in which the intermediate
is not released into the bulk medium, i.e., substrate channeling. Unexpectedly,
single-turnover kinetic experiments of the coupled PRODH-P5CDH reaction revealed
that the rate of NADH formation is 20-fold slower than the steady-state turnover
number for the overall reaction, implying that catalytic cycling speeds up
throughput. We show that the limiting rate constant observed for NADH formation
in the first turnover increases by almost 40-fold after multiple turnovers,
achieving half of the steady-state value after 15 turnovers. These results
suggest that EcPutA achieves an activated channeling state during the approach to
steady state and is thus a new example of a hysteretic enzyme. Potential
underlying causes of activation of channeling are discussed.
PMID- 24352663
TI - miR-185 is an independent prognosis factor and suppresses tumor metastasis in
gastric cancer.
AB - miR-185 has been identified as an important factor in several cancers such as
breast cancer, ovarial cancer, and prostate cancer. However, its effect and
prognostic value in gastric cancer are still poorly known. In this study, we
found that the expression levels of miR-185 were strongly downregulated in
gastric cancer and associated with clinical stage and the presence of lymph node
metastases. Moreover, miR-185 might independently predict OS and RFS in gastric
cancer. We further found that upregulation of miR-185 inhibited the proliferation
and metastasis of gastric cancer cells in vitro and in vivo. Taken together, our
findings demonstrate that the miR-185 is important for gastric cancer initiation
and progression and holds promise as a prognostic biomarker to predict survival
and relapse in gastric cancer. It is also a potential therapeutic tool to improve
clinical outcomes in the above disease.
PMID- 24352664
TI - Measurement of oxygen consumption in children undergoing cardiac catheterization:
comparison between mass spectrometry and the breath-by-breath method.
AB - Accurate measurement of oxygen consumption (VO2) is important to precise
calculation of blood flow using the Fick equation. This study aimed to validate
the breath-by-breath method (BBBM) of measuring oxygen consumption VO2 compared
with respiratory mass spectroscopy (MS) for intubated children during cardiac
catheterization. The study used MS and BBBM to measure VO2 continuously and
simultaneously for 10 min in consecutive anesthetized children undergoing cardiac
catheterization who were intubated with a cuffed endotracheal tube, ventilated
mechanically, and hemodynamically stable, with normal body temperature. From 26
patients, 520 data points were obtained. The mean VO2 was 94.5 ml/min (95 %
confidence interval [CI] 65.7-123.3 ml/min) as measured by MS and 91.4 ml/min (95
% CI 64.9-117.9 ml/min) as measured by BBBM. The mean difference in VO2
measurements between MS and BBBM (3.1 ml/min; 95 % CI -1.7 to +7.9 ml/min) was
not significant (p = 0.19). The MS and BBBM VO2 measurements were highly
correlated (R (2) = 0.98; P < 0.0001). Bland-Altman analysis showed good
correspondence between MS and BBBM, with a mean difference of -3.01 and 95 %
limits of agreement ranging from -26.2 to +20.0. The mean VO2 indexed to body
surface area did not differ significantly between MS and BBBM (3.4 ml/min m(2);
95 % CI -1.4 to 8.2; p = 0.162). The mean difference and limits of agreement were
-3.8 ml/min m(2) (range, -19.9 to 26.7). Both MS and BBBM may be used to measure
VO2 in anesthetized intubated children undergoing cardiac catheterization. The
two methods demonstrated excellent agreement. However, BBBM may be more suited to
clinical use with children.
PMID- 24352665
TI - Fetal echocardiographic measurements and the need for neonatal surgical
intervention in Tetralogy of Fallot.
AB - BACKGROUND: This study aimed to evaluate fetal echocardiographic measurements at
the time of the first fetal echocardiogram as predictors of neonatal outcome for
tetralogy of Fallot (TOF). METHODS: The study reviewed all infants with a
prenatal diagnosis of TOF from January 2004 to June 2011. Aortic valve (AoV),
pulmonary valve (PV), main pulmonary artery (MPA), left and right pulmonary
artery diameters, and ductus arteriosus flow were evaluated on fetal
echocardiograms, and associations between the fetal echocardiogram and the
neonatal echocardiogram measurements and outcomes were assessed. RESULTS: The
study identified 67 TOF patients who had an initial fetal echocardiogram at a
mean gestational age of 25.0 +/- 5.2 weeks. Patients with absent PV syndrome or
major aortopulmonary collaterals were excluded from the study, as were those
without anterograde pulmonary blood flow at the first fetal echocardiogram. Of
the remaining 44 patients, 10 were ductal dependent and required neonatal
surgery. Infants who were ductal dependent had lower fetal PV (-5.38 +/- 2.95 vs.
-3.51 +/- 1.66; p < 0.05) and MPA (-3.94 +/- 1.66 vs. -2.87 +/- 1.04; p < 0.05) z
scores. A fetal PV z-score of -5 predicted ductal dependence with 78 %
sensitivity and 87 % specificity, and a PV z-score of -3 showed 100 % sensitivity
and 34 % specificity (p < 0.001). Fetuses with a reversed left-to-right flow
across the ductus arteriosus (DA) were more likely to be ductal dependent (odds
ratio, 25; p < 0.001) than those who had normal ductal flow. CONCLUSIONS: In TOF,
fetal PV and MPA z-scores and direction of the DA blood flow predict neonatal
ductal dependence. Patients with fetal PV z-scores lower than -3 or any left-to
right flow at the level of the DA should be admitted to a center where
prostaglandin is available.
PMID- 24352666
TI - Prenatal detection of congenital heart disease: time for a breakthrough.
PMID- 24352669
TI - Modelling the mechanics of partially mineralized collagen fibrils, fibres and
tissue.
AB - Progressive stiffening of collagen tissue by bioapatite mineral is important
physiologically, but the details of this stiffening are uncertain. Unresolved
questions about the details of the accommodation of bioapatite within and upon
collagen's hierarchical structure have posed a central hurdle, but recent
microscopy data resolve several major questions. These data suggest how collagen
accommodates bioapatite at the lowest relevant hierarchical level (collagen
fibrils), and suggest several possibilities for the progressive accommodation of
bioapatite at higher hierarchical length scales (fibres and tissue). We developed
approximations for the stiffening of collagen across spatial hierarchies based
upon these data, and connected models across hierarchies levels to estimate
mineralization-dependent tissue-level mechanics. In the five possible sequences
of mineralization studied, percolation of the bioapatite phase proved to be an
important determinant of the degree of stiffening by bioapatite. The models were
applied to study one important instance of partially mineralized tissue, which
occurs at the attachment of tendon to bone. All sequences of mineralization
considered reproduced experimental observations of a region of tissue between
tendon and bone that is more compliant than either tendon or bone, but the size
and nature of this region depended strongly upon the sequence of mineralization.
These models and observations have implications for engineered tissue scaffolds
at the attachment of tendon to bone, bone development and graded biomimetic
attachment of dissimilar hierarchical materials in general.
PMID- 24352670
TI - Flagellar dynamics of a connected chain of active, polar, Brownian particles.
AB - We show that active, self-propelled particles that are connected together to form
a single chain that is anchored at one end can produce the graceful beating
motions of flagella. Changing the boundary condition from a clamp to a pivot at
the anchor leads to steadily rotating tight coils. Strong noise in the system
disrupts the regularity of the oscillations. We use a combination of detailed
numerical simulations, mean-field scaling analysis and first passage time theory
to characterize the phase diagram as a function of the filament length, passive
elasticity, propulsion force and noise. Our study suggests minimal experimental
tests for the onset of oscillations in an active polar chain.
PMID- 24352667
TI - Current concepts: tissue engineering and regenerative medicine applications in
the ankle joint.
AB - Tissue engineering and regenerative medicine (TERM) has caused a revolution in
present and future trends of medicine and surgery. In different tissues, advanced
TERM approaches bring new therapeutic possibilities in general population as well
as in young patients and high-level athletes, improving restoration of biological
functions and rehabilitation. The mainstream components required to obtain a
functional regeneration of tissues may include biodegradable scaffolds, drugs or
growth factors and different cell types (either autologous or heterologous) that
can be cultured in bioreactor systems (in vitro) prior to implantation into the
patient. Particularly in the ankle, which is subject to many different injuries
(e.g. acute, chronic, traumatic and degenerative), there is still no definitive
and feasible answer to 'conventional' methods. This review aims to provide
current concepts of TERM applications to ankle injuries under preclinical and/or
clinical research applied to skin, tendon, bone and cartilage problems. A
particular attention has been given to biomaterial design and scaffold processing
with potential use in osteochondral ankle lesions.
PMID- 24352671
TI - Photosynthetic light harvesting: excitons and coherence.
AB - Photosynthesis begins with light harvesting, where specialized pigment-protein
complexes transform sunlight into electronic excitations delivered to reaction
centres to initiate charge separation. There is evidence that quantum coherence
between electronic excited states plays a role in energy transfer. In this
review, we discuss how quantum coherence manifests in photosynthetic light
harvesting and its implications. We begin by examining the concept of an exciton,
an excited electronic state delocalized over several spatially separated
molecules, which is the most widely available signature of quantum coherence in
light harvesting. We then discuss recent results concerning the possibility that
quantum coherence between electronically excited states of donors and acceptors
may give rise to a quantum coherent evolution of excitations, modifying the
traditional incoherent picture of energy transfer. Key to this (partially)
coherent energy transfer appears to be the structure of the environment, in
particular the participation of non-equilibrium vibrational modes. We discuss the
open questions and controversies regarding quantum coherent energy transfer and
how these can be addressed using new experimental techniques.
PMID- 24352673
TI - Separate enrichment analysis of pathways for up- and downregulated genes.
AB - Two strategies are often adopted for enrichment analysis of pathways: the
analysis of all differentially expressed (DE) genes together or the analysis of
up- and downregulated genes separately. However, few studies have examined the
rationales of these enrichment analysis strategies. Using both microarray and RNA
seq data, we show that gene pairs with functional links in pathways tended to
have positively correlated expression levels, which could result in an imbalance
between the up- and downregulated genes in particular pathways. We then show that
the imbalance could greatly reduce the statistical power for finding disease
associated pathways through the analysis of all-DE genes. Further, using gene
expression profiles from five types of tumours, we illustrate that the separate
analysis of up- and downregulated genes could identify more pathways that are
really pertinent to phenotypic difference. In conclusion, analysing up- and
downregulated genes separately is more powerful than analysing all of the DE
genes together.
PMID- 24352674
TI - Unzipping bird feathers.
AB - The bird feather vane can be separated into two parts by pulling the barbs apart.
The original state can be re-established easily by lightly stroking through the
feather. Hooklets responsible for holding vane barbs together are not damaged by
multiple zipping and unzipping cycles. Because numerous microhooks keep the
integrity of the feather, their properties are of great interest for
understanding mechanics of the entire feather structure. This study was
undertaken to estimate the separation force of single hooklets and their arrays
using force measurement of an unzipping feather vane. The hooklets usually
separate in some number synchronously (20 on average) with the highest observed
separation force of 1.74 mN (average force 0.27 mN), whereas the single hooklet
separation force was 14 MUN. A simple numerical model was suggested for a better
understanding of zipping and unzipping behaviour in feathers. The model
demonstrates features similar to those observed in experiments.
PMID- 24352672
TI - Non-random biodiversity loss underlies predictable increases in viral disease
prevalence.
AB - Disease dilution (reduced disease prevalence with increasing biodiversity) has
been described for many different pathogens. Although the mechanisms causing this
phenomenon remain unclear, the disassembly of communities to predictable subsets
of species, which can be caused by changing climate, land use or invasive
species, underlies one important hypothesis. In this case, infection prevalence
could reflect the competence of the remaining hosts. To test this hypothesis, we
measured local host species abundance and prevalence of four generalist aphid
vectored pathogens (barley and cereal yellow dwarf viruses) in a ubiquitous
annual grass host at 10 sites spanning 2000 km along the North American West
Coast. In laboratory and field trials, we measured viral infection as well as
aphid fecundity and feeding preference on several host species. Virus prevalence
increased as local host richness declined. Community disassembly was non-random:
ubiquitous hosts dominating species-poor assemblages were among the most
competent for vector production and virus transmission. This suggests that non
random biodiversity loss led to increased virus prevalence. Because diversity
loss is occurring globally in response to anthropogenic changes, such work can
inform medical, agricultural and veterinary disease research by providing
insights into the dynamics of pathogens nested within a complex web of
environmental forces.
PMID- 24352675
TI - More than just slippery: the impact of biofilm on the attachment of non-sessile
freshwater mayfly larvae.
AB - While terrestrial insects can usually attach directly to a substrate, for aquatic
insects the situation is more complicated owing to the presence of a biofilm on
the primary substrates. This important fact has been neither the subject of
investigation nor commonly taken into account in the interpretation of functional
aspects of attachment in mobile freshwater animals. In this study, we investigate
the impact of a biofilm on the attachment of living mayfly larvae. We performed
in vivo attachment experiments in a flow channel using different substrates with
defined surface roughness. Additionally, we measured friction forces directly
generated by dissected tarsal claws on the same substrates. On substrates with
smooth or slightly rough surfaces, which have little or no surface irregularities
large enough for the claws to grasp, the presence of a biofilm significantly
increases the friction force of claws. Consequently, larvae can endure higher
flow velocities on these smooth substrates. The opposite effect takes place on
rough substrates, where the friction force of claws decreases in the presence of
a biofilm. Consequently, a biofilm is a critical ecological structure for these
larvae, and other aquatic organisms, not only as a food source but also as a
factor influencing attachment ability.
PMID- 24352668
TI - Philosophy of voltage-gated proton channels.
AB - In this review, voltage-gated proton channels are considered from a mainly
teleological perspective. Why do proton channels exist? What good are they? Why
did they go to such lengths to develop several unique hallmark properties such as
extreme selectivity and DeltapH-dependent gating? Why is their current so
minuscule? How do they manage to be so selective? What is the basis for our
belief that they conduct H(+) and not OH(-)? Why do they exist in many species as
dimers when the monomeric form seems to work quite well? It is hoped that
pondering these questions will provide an introduction to these channels and a
way to logically organize their peculiar properties as well as to understand how
they are able to carry out some of their better-established biological functions.
PMID- 24352676
TI - Nanointerfacial strength between non-collagenous protein and collagen fibrils in
antler bone.
AB - Antler bone displays considerable toughness through the use of a complex
nanofibrous structure of mineralized collagen fibrils (MCFs) bound together by
non-collagenous proteins (NCPs). While the NCP regions represent a small volume
fraction relative to the MCFs, significant surface area is evolved upon failure
of the nanointerfaces formed at NCP-collagen fibril boundaries. The mechanical
properties of nanointerfaces between the MCFs are investigated directly in this
work using an in situ atomic force microscopy technique to pull out individual
fibrils from the NCP. Results show that the NCP-fibril interfaces in antler bone
are weak, which highlights the propensity for interface failure at the nanoscale
in antler bone and extensive fibril pullout observed at antler fracture surfaces.
The adhesion between fibrils and NCP is additionally suggested as being rate
dependent, with increasing interfacial strength and fracture energy observed when
pullout velocity decreases.
PMID- 24352677
TI - Circadian clocks optimally adapt to sunlight for reliable synchronization.
AB - Circadian oscillation provides selection advantages through synchronization to
the daylight cycle. However, a reliable clock must be designed through two
conflicting properties: entrainability to synchronize internal time with periodic
stimuli such as sunlight, and regularity to oscillate with a precise period.
These two aspects do not easily coexist, because better entrainability favours
higher sensitivity which may sacrifice regularity. To investigate conditions for
satisfying the two properties, we analytically calculated the optimal phase
response curve with a variational method. Our results indicate an existence of a
dead zone, i.e. a time period during which input stimuli neither advance nor
delay the clock. A dead zone appears only when input stimuli obey the time course
of actual solar radiation, but a simple sine curve cannot yield a dead zone. Our
calculation demonstrates that every circadian clock with a dead zone is optimally
adapted to the daylight cycle.
PMID- 24352678
TI - Alignment of crystal orientations of the multi-domain photonic crystals in
Parides sesostris wing scales.
AB - It is known that the wing scales of the emerald-patched cattleheart butterfly,
Parides sesostris, contain gyroid-type photonic crystals, which produce a green
structural colour. However, the photonic crystal is not a single crystal that
spreads over the entire scale, but it is separated into many small domains with
different crystal orientations. As a photonic crystal generally has band gaps at
different frequencies depending on the direction of light propagation, it seems
mysterious that the scale is observed to be uniformly green under an optical
microscope despite the multi-domain structure. In this study, we have carefully
investigated the structure of the wing scale and discovered that the crystal
orientations of different domains are not perfectly random, but there is a
preferred crystal orientation that is aligned along the surface normal of the
scale. This finding suggests that there is an additional factor during the
developmental process of the microstructure that regulates the crystal
orientation.
PMID- 24352679
TI - Constructing and characterizing a bioactive small molecule and microRNA
association network for Alzheimer's disease.
AB - Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Much effort
has been devoted to developing effective therapeutic agents. Recently, targeting
microRNAs (miRNAs) with small molecules has become a novel therapy for human
diseases. In this study, we present a systematic computational approach to
construct a bioactive Small molecule and miRNA association Network in AD (SmiRN
AD), which is based on the gene expression signatures of bioactive small molecule
perturbation and AD-related miRNA regulation. We also performed topological and
functional analysis of the SmiRN-AD from multiple perspectives. At the
significance level of p <= 0.01, 496 small molecule-miRNA associations, including
25 AD-related miRNAs and 275 small molecules, were recognized and used to
construct the SmiRN-AD. The drugs that were connected with the same miRNA tended
to share common drug targets (p = 1.72 * 10(-4)) and belong to the same
therapeutic category (p = 4.22 * 10(-8)). The miRNAs that were linked to the same
small molecule regulated more common miRNA targets (p = 6.07 * 10(-3)). Further
analysis of the positive connections (quinostatin and miR-148b, amantadine and
miR-15a) and the negative connections (melatonin and miR-30e-5p) indicated that
our large-scale predictions afforded specific biological insights into AD
pathogenesis and therapy. This study proposes a holistic strategy for deciphering
the associations between small molecules and miRNAs in AD, which may be helpful
for developing a novel effective miRNA-associated therapeutic strategy for AD. A
comprehensive database for the SmiRN-AD and the differential expression patterns
of the miRNA targets in AD is freely available at
http://bioinfo.hrbmu.edu.cn/SmiRN-AD/.
PMID- 24352681
TI - Topography-controlled alignment of DNA origami nanotubes on nanopatterned
surfaces.
AB - The controlled positioning of DNA nanostructures on technologically relevant
surfaces represents a major goal along the route toward the full-scale
integration of DNA-based materials into nanoelectronic and sensor devices.
Previous attempts to arrange DNA nanostructures into defined arrays mostly relied
on top-down lithographic patterning techniques combined with chemical surface
functionalization. Here we combine two bottom-up techniques for nanostructure
fabrication, i.e., self-organized nanopattern formation and DNA origami self
assembly, in order to demonstrate the electrostatic self-alignment of DNA
nanotubes on topographically patterned silicon surfaces. Self-organized nanoscale
ripple patterns with periodicities ranging from 20 nm to 50 nm are fabricated by
low-energy ion irradiation and serve as substrates for DNA origami adsorption.
Electrostatic interactions with the charged surface oxide during adsorption
direct the DNA origami nanotubes to the ripple valleys and align them parallel to
the ripples. By optimizing the pattern dimensions and the Debye length of the
adsorption buffer, we obtain an alignment yield of ~70%. Since this novel and
versatile approach does not rely on any chemical functionalization of the surface
or the DNA nanotubes, it can be applied to virtually any substrate material and
any top-down or bottom-up nanopatterning technique. This technique thus may
enable the wafer-scale fabrication of ordered arrays of functional DNA-based
nanowires.
PMID- 24352682
TI - The golden ratio and Loshu-Fibonacci Diagram: novel research view on relationship
of Chinese medicine and modern biology.
AB - Associating geometric arrangements of 9 Loshu numbers modulo 5, investigating
property of golden rectangles and characteristics of Fibonacci sequence modulo 10
as well as the two subsequences of its modular sequence by modulo 5, the Loshu
Fibonacci Diagram is created based on strict logical deduction in this paper,
which can disclose inherent relationship among Taiji sign, Loshu and Fibonacci
sequence modulo 10 perfectly and unite such key ideas of holism, symmetry,
holographic thought and yin-yang balance pursuit from Chinese medicine as a
whole. Based on further analysis and reasoning, the authors discover that taking
the golden ratio and Loshu-Fibonacci Diagram as a link, there is profound and
universal association existing between researches of Chinese medicine and modern
biology.
PMID- 24352680
TI - TLR2 and TLR4 in autoimmune diseases: a comprehensive review.
AB - Autoimmune diseases are immune disorders characterized by T cell hyperactivity
and B cell overstimulation leading to overproduction of autoantibodies. Although
the pathogenesis of various autoimmune diseases remains to be elucidated,
environmental factors have been thought to contribute to the initiation and
maintenance of auto-respond inflammation. Toll-like receptors (TLRs) are pattern
recognition receptors belonging to innate immunity that recognize and defend
invading microorganisms. Besides these exogenous pathogen-associated molecular
patterns, TLRs can also bind with damage-associated molecular patterns produced
under strike or by tissue damage or cells apoptosis. It is believed that TLRs
build a bridge between innate immunity and autoimmunity. There are five adaptors
to TLRs including MyD88, TRIF, TIRAP/MAL, TRAM, and SARM. Upon activation, TLRs
recruit specific adaptors to initiate the downstream signaling pathways leading
to the production of inflammatory cytokines and chemokines. Under certain
circumstances, ligation of TLRs drives to aberrant activation and unrestricted
inflammatory responses, thereby contributing to the perpetuation of inflammation
in autoimmune diseases. In the past, most studies focused on the intracellular
TLRs, such as TLR3, TLR7, and TLR9, but recent studies reveal that cell surface
TLRs, especially TLR2 and TLR4, also play an essential role in the development of
autoimmune diseases and afford multiple therapeutic targets. In this review, we
summarized the biological characteristics, signaling mechanisms of TLR2/4, the
negative regulators of TLR2/4 pathway, and the pivotal function of TLR2/4 in the
pathogenesis of autoimmune diseases including rheumatoid arthritis, systemic
lupus erythematosus, systemic sclerosis, Sjogren's syndrome, psoriasis, multiple
sclerosis, and autoimmune diabetes.
PMID- 24352683
TI - Cure for acquired immunodeficiency syndrome--a global battle.
PMID- 24352684
TI - Is high fidelity to supported employment equally attainable in small and large
communities?
AB - Individual Placement and Support (IPS) is an evidence-based model to help people
with serious mental illness achieve employment. This study examined variation in
model adherence in small and large communities. We compared program-level ratings
on a standardized 25-item IPS fidelity scale (range = 25-125) for 79 sites in
eight states categorized by local community size. Programs in large and small
communities achieved comparable fidelity scores (mean = 100 and 104,
respectively). Fidelity-outcome correlations within the two groups were both of
moderate size. As a practical guide, the IPS fidelity scale is suitable for use
in both small and large communities.
PMID- 24352686
TI - Bioresponsive controlled release from mesoporous silica nanocontainers with
glucometer readout.
AB - A novel sensing platform for monitoring small molecules without the need for
sample separation and washing is developed by using a commercialized personal
glucose meter based on bioresponsive controlled release of glucose from aptamer
gated mesoporous silica nanocontainers.
PMID- 24352685
TI - Neuroticism and extraversion are associated with amygdala resting-state
functional connectivity.
AB - The personality traits neuroticism and extraversion are differentially related to
socioemotional functioning and susceptibility to affective disorders. However,
the neurobiology underlying this differential relationship is still poorly
understood. This discrepancy could perhaps best be studied by adopting a brain
connectivity approach. Whereas the amygdala has repeatedly been linked to
neuroticism and extraversion, no study has yet focused on the intrinsic
functional architecture of amygdala-centered networks in relation to both traits.
To this end, seed-based correlation analysis was employed to reveal amygdala
resting-state functional connectivity (RSFC) and its associations with
neuroticism and extraversion in 50 healthy participants. Higher neuroticism
scores were associated with increased amygdala RSFC with the precuneus, and
decreased amygdala RSFC with the temporal poles, insula, and superior temporal
gyrus (p < .05, cluster corrected). Conversely, higher extraversion scores were
associated with increased amygdala RSFC with the putamen, temporal pole, insula,
and several regions of the occipital cortex (p < .05, cluster corrected). The
shifts in amygdala RSFC associated with neuroticism may relate to the less
adaptive perception and processing of self-relevant and socioemotional
information that is frequently seen in neurotic individuals, whereas the amygdala
RSFC pattern associated with extraversion may relate to the heightened reward
sensitivity and enhanced socioemotional functioning in extraverts. We hypothesize
that the variability in amygdala RSFC observed in the present study could
potentially link neuroticism and extraversion to the neurobiology underlying
increased susceptibility or resilience to affective disorders.
PMID- 24352687
TI - An automated synthesis-purification-sample-management platform for the
accelerated generation of pharmaceutical candidates.
AB - A flexible and integrated flow-chemistry-synthesis-purification compound
generation and sample-management platform has been developed to accelerate the
production of small-molecule organic-compound drug candidates in pharmaceutical
research. Central to the integrated system is a Mitsubishi robot, which hands off
samples throughout the process to the next station, including synthesis and
purification, sample dispensing for purity and quantification analysis, dry-down,
and aliquot generation.
PMID- 24352688
TI - Assessing the trustworthiness of the guideline for management of high blood
pressure in adults.
PMID- 24352691
TI - Extraction of target specimens from bioholographic images using interactive graph
cuts.
AB - It is necessary to extract target specimens from bioholographic images for high
level analysis such as object identification, recognition, and tracking with the
advent of application of digital holographic microscopy to transparent or semi
transparent biological specimens. We present an interactive graph cuts approach
to segment the needed target specimens in the reconstructed bioholographic
images. This method combines both regional and boundary information and is robust
to extract targets with weak boundaries. Moreover, this technique can achieve
globally optimal results while minimizing an energy function. We provide a
convenient user interface, which can easily differentiate the
foreground/background for various types of holographic images, as well as a
dynamically modified coefficient, which specifies the importance of the regional
and boundary information. The extracted results from our scheme have been
compared with those from an advanced level-set-based segmentation method using an
unbiased comparison algorithm. Experimental results show that this interactive
graph cut technique can not only extract different kinds of target specimens in
bioholographic images, but also yield good results when there are multiple
similar objects in the holographic image or when the object boundaries are very
weak.
PMID- 24352692
TI - Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance
spectroscopy and laser Doppler flowmetry.
AB - The tissue fraction of red blood cells (RBCs) and their oxygenation and speed
resolved perfusion are estimated in absolute units by combining diffuse
reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF). The DRS spectra
(450 to 850 nm) are assessed at two source-detector separations (0.4 and 1.2 mm),
allowing for a relative calibration routine, whereas LDF spectra are assessed at
1.2 mm in the same fiber-optic probe. Data are analyzed using nonlinear
optimization in an inverse Monte Carlo technique by applying an adaptive
multilayered tissue model based on geometrical, scattering, and absorbing
properties, as well as RBC flow-speed information. Simulations of 250 tissue-like
models including up to 2000 individual blood vessels were used to evaluate the
method. The absolute root mean square (RMS) deviation between estimated and true
oxygenation was 4.1 percentage units, whereas the relative RMS deviations for the
RBC tissue fraction and perfusion were 19% and 23%, respectively. Examples of in
vivo measurements on forearm and foot during common provocations are presented.
The method offers several advantages such as simultaneous quantification of RBC
tissue fraction and oxygenation and perfusion from the same, predictable,
sampling volume. The perfusion estimate is speed resolved, absolute (% RBC*mm/s),
and more accurate due to the combination with DRS.
PMID- 24352689
TI - Attention to memory: orienting attention to sound object representations.
AB - Despite a growing acceptance that attention and memory interact, and that
attention can be focused on an active internal mental representation (i.e.,
reflective attention), there has been a paucity of work focusing on reflective
attention to 'sound objects' (i.e., mental representations of actual sound
sources in the environment). Further research on the dynamic interactions between
auditory attention and memory, as well as its degree of neuroplasticity, is
important for understanding how sound objects are represented, maintained, and
accessed in the brain. This knowledge can then guide the development of training
programs to help individuals with attention and memory problems. This review
article focuses on attention to memory with an emphasis on behavioral and
neuroimaging studies that have begun to explore the mechanisms that mediate
reflective attentional orienting in vision and more recently, in audition.
Reflective attention refers to situations in which attention is oriented toward
internal representations rather than focused on external stimuli. We propose four
general principles underlying attention to short-term memory. Furthermore, we
suggest that mechanisms involved in orienting attention to visual object
representations may also apply for orienting attention to sound object
representations.
PMID- 24352693
TI - Shock wave and modeling study of the thermal decomposition reactions of
pentafluoroethane and 2-H-heptafluoropropane.
AB - The thermal decomposition reactions of CF3CF2H and CF3CFHCF3 have been studied in
shock waves by monitoring the appearance of CF2 radicals. Temperatures in the
range 1400-2000 K and Ar bath gas concentrations in the range (2-10) * 10(-5) mol
cm(-3) were employed. It is shown that the reactions are initiated by C-C bond
fission and not by HF elimination. Differing conclusions in the literature about
the primary decomposition products, such as deduced from experiments at very low
pressures, are attributed to unimolecular falloff effects. By increasing the
initial reactant concentrations in Ar from 60 to 1000 ppm, a retardation of CF2
formation was observed while the final CF2 yields remained close to two CF2 per
C2F5H or three CF2 per C3F7H decomposed. This is explained by secondary
bimolecular reactions which lead to comparably stable transient species like
CF3H, releasing CF2 at a slower rate. Quantum-chemical calculations and kinetic
modeling help to identify the reaction pathways and provide estimates of rate
constants for a series of primary and secondary reactions in the decomposition
mechanism.
PMID- 24352694
TI - Evidence for multiple MHC class II beta loci in New Zealand's critically
endangered kakapo, Strigops habroptilus.
AB - Immunologically important genes of the major histocompatibility complex (MHC)
have been characterized in a number of avian species with the general finding of
considerable variation in size and structural organization among organisms. A
range of nonpasserines which represent early-diverging Neoave lineages have been
described as having only one MHC class II beta locus potentially leading to the
conclusion that this is the ancestral condition. Here, we examine the monotypic,
early-diverging, critically endangered kakapo, Strigops habroptilus, for allelic
variation at MHC class II beta exon 2, as part of species' recovery efforts. We
found two to four confirmed sequence variants per individual indicating the
presence of more than one MHC class II beta locus. Given the kakapo's basal
evolutionary status, evidence for multiple MHC class II beta loci seems to
counter the proposed mono-locus history of modern birds. However, MHC gene
duplication, maintenance, and loss among and within bird species may confound
avian relationships making it difficult to elucidate the ancestral state. This
study adds essential data for disentangling the course of MHC structural
evolution in birds.
PMID- 24352695
TI - Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial
ovarian cancer in a Chinese population.
AB - This study investigated the association between IL-27 gene polymorphisms and
susceptibility to epithelial ovarian cancer in a Chinese population and discusses
the risk factors associated with survival time. We collected data on 229 patients
diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long
clinical follow-up period. Polymerase chain reaction-restriction fragment length
polymorphism was performed to determine the genotype of IL-27 gene polymorphisms.
Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene
polymorphisms was explored by Kaplan-Meier analysis and Cox proportional hazards
modeling. Significant differences for genotype frequencies of both SNP sites were
found between cases and controls. Both allele G frequencies were significantly
greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] =
1.333, 95% confidence interval [CI] = 1.133-1.567; rs17855750: 0.146 vs. 0.083, P
= 0.001, OR = 1.766, 95% CI = 1.258-2.481). Haplotype analysis showed haplotypes
AG, GT and GG were associated with increased ovarian cancer susceptibility while
AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non
optimal cytoreductive surgery (residual tumor >=1 cm) were poor prognostic
factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage
was found to be the only independent significant prognostic factor by Cox
proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was
significantly decreased in ovarian cancer patients (P < 0.0001), while no
significant relationship was found between IL-27p28 mRNA expression and
polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively).
Our study suggests that IL-27 gene polymorphisms may be involved in the
susceptibility to epithelial ovarian cancer, but not in survival in a clinic
based Chinese population. Haplotype analysis of these two SNPs seems to be an
important mark to predict the disease susceptibility. Advanced FIGO stage, as the
only significant, independent risk factor, predicts poor clinical outcomes for
patients diagnosed with epithelial ovarian cancer. The decreased expression of IL
27p28 mRNA in ovarian cancer might indicate the antitumor activities of this
novel cytokine.
PMID- 24352697
TI - Reversed better-than-average effect in direct comparisons of nonsocial stimuli
depends on the set size.
AB - Studies on direct comparative judgments typically show that, for items that are
positively evaluated, a single item randomly drawn from a larger set of similar
items tends to be judged as better than average (the BTA effect). However,
Windschitl, Conybeare, and Krizan (2008) demonstrated that, under timing
conditions that do not favor focusing attention on the single item, the reversal
of the BTA effect occurs. We report two experiments showing that the magnitude of
the reversed BTA effect increases as a function of the size of a multiitem
referent with which a single item target is compared. Specifically, in direct
comparative judgments of the attractiveness of positively evaluated objects (nice
looking cloth buttons, attractive buildings, or cupcakes), underestimation of the
attractiveness of singletons, as compared with a multiitem set (reversed BTA
effect), increased with the increased set size. Analysis of absolute judgments
obtained for singletons and for small and large multiitem sets suggests that, for
attractive stimuli, both the reversed BTA effect in comparative judgments and its
sensitivity to set size occur as a result of a positive relationship between set
size and perceived attractiveness in absolute judgments.
PMID- 24352698
TI - Integrated random-aligned carbon nanotube layers: deformation mechanism under
compression.
AB - Carbon nanotubes have the potential to construct highly compressible and elastic
macroscopic structures such as films, aerogels and sponges. The structure-related
deformation mechanism determines the mechanical behavior of those structures and
niche applications. Here, we show a novel strategy to integrate aligned and
random nanotube layers and reveal their deformation mechanism under uniaxial
compression with a large range of strain and cyclic testing. Integrated nanotube
layers deform sequentially with different mechanisms due to the distinct
morphology of each layer. While the aligned layer forms buckles under
compression, nanotubes in the random layer tend to be parallel and form bundles,
resulting in the integration of quite different properties (strength and
stiffness) and correspondingly distinct plateau regions in the stress-strain
curves. Our results indicate a great promise of constructing hierarchical carbon
nanotube structures with tailored energy absorption properties, for applications
such as cushioning and buffering layers in microelectromechanical systems.
PMID- 24352696
TI - MicroRNA-339-5p down-regulates protein expression of beta-site amyloid precursor
protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced
in brain tissue specimens of Alzheimer disease subjects.
AB - Alzheimer disease (AD) results, in part, from the excess accumulation of the
amyloid-beta (Abeta) peptide as neuritic plaques in the brain. The short Abeta
peptide is derived from the large transmembrane Abeta precursor protein (APP).
The rate-limiting step in the production of Abeta from APP is mediated by the
beta-site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to
excess Abeta deposition is implicated in sporadic AD. Thus, elucidating the full
complement of regulatory pathways that control BACE1 expression is key to
identifying novel drug targets central to the Abeta-generating process. MicroRNAs
(miRNAs) are expected to participate in this molecular network. Here, we
identified a known miRNA, miR-339-5p, as a key contributor to this regulatory
network. Two distinct miR-339-5p target sites were predicted in the BACE1 3'-UTR
by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3'-UTR reporter
construct resulted in significant reduction in reporter expression. Mutation of
both target sites eliminated this effect. Delivery of the miR-339-5p mimic also
significantly inhibited expression of BACE1 protein in human glioblastoma cells
and human primary brain cultures. Delivery of target protectors designed against
the miR-339-5p BACE1 3'-UTR target sites in primary human brain cultures
significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to
be significantly reduced in brain specimens isolated from AD patients as compared
with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in
human brain cells and is most likely dysregulated in at least a subset of AD
patients making this miRNA a novel drug target.
PMID- 24352699
TI - The molecular mechanism of NELL2 movement and secretion in hippocampal progenitor
HiB5 cells.
AB - Neural epidermal growth factor-like protein-like 2 (NELL2) is a secreted
glycoprotein that is predominantly expressed in the nervous system, but little is
known about the intracellular movement and secretion mechanism of this protein.
By monitoring the localization and movements of enhanced green fluorescent
protein (EGFP)-labeled NELL2 in living cultured hippocampal neuroprogenitor HiB5
cells, we determined the subcellular localization of NELL2 and its intracellular
movement and secretion mechanism. Cterminal EGFP-fused NELL2 showed a typical
expression pattern of secreted proteins, especially with respect to its
localization in the endoplasmic reticulum, Golgi apparatus, and punctate
structures. Vesicles containing NELL2 exhibited bidirectional movement in HiB5
cells. The majority of the vesicles (70.1%) moved in an anterograde direction
with an average velocity of 0.454 MUm/s, whereas some vesicles (28.7%) showed
retrograde movement with an average velocity of 0.302 MUm/s. The movement
patterns of NELL2 vesicles were dependent upon the presence of microtubules in
HiB5 cells. Anterograde movement of NELL2 did not lead to a detectable
accumulation of NELL2 in the peripheral region of the cell, indicating that it
was secreted into the culture medium. We also showed that the N-terminal 29 amino
acids of NELL2 were important for secretion of this protein. Taken together,
these results strongly suggest that the N-terminal region of NELL2 determines
both the pattern of its intracellular expression and transport of NELL2 vesicles
by high-velocity movement. Therefore, NELL2 may affect the cellular activity of
cells in a paracrine or autocrine manner.
PMID- 24352700
TI - Extending the electron spin coherence time of atomic hydrogen by dynamical
decoupling.
AB - We study the electron spin decoherence of encapsulated atomic hydrogen in
octasilsesquioxane cages induced by the (1)H and (29)Si nuclear spin bath. By
applying the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence we significantly
suppress the low-frequency noise due to nuclear spin flip-flops up to the point
where a maximum T2 = 56 MUs is observed. Moreover, dynamical decoupling with the
CPMG sequence reveals the existence of two other sources of decoherence: first, a
classical magnetic field noise imposed by the (1)H nuclear spins of the cage
organic substituents, which can be described by a virtual fluctuating magnetic
field with the proton Larmor frequency, and second, decoherence due to
anisotropic hyperfine coupling between the electron and the inner (29)Si spins of
the cage.
PMID- 24352701
TI - SOCS2 inhibited mitochondria biogenesis via inhibiting p38 MAPK/ATF2 pathway in
C2C12 cells.
AB - In order to investigate the mechanism of suppressor of cytokine signaling 2
(SOCS2) on mitochondrial biogenesis, RNA interference and over-expression plasmid
vectors of SOCS2 were used to transfect murine skeletal muscle C2C12 cells.
Results demonstrated that over-expression of SOCS2 inhibited the differentiation
of C2C12 cells, and reduced the expression of MyHC, MyoD and MyoG while elevated
the protein expression of MSTN. Meanwhile the expression of PGC-1alpha, MDH, CPT
1 were significantly elevated in the RNA interference of SOCS2 group which were
decreased in SOCS2 overexpression group. However, there was no change on the
expression of UCP1 in both two groups. JC-1 dyeing showed overexpression of SOCS2
decreased the mitochondrial membrane potential and results of immunofluorescence,
real-time PCR and western blotting indicated the increase expression of Cyt c,
while interference SOCS2 had the opposite effects in C2C12 cells. Moreover,
interference of SOCS2 elevated the p38 phosphorylation level then further
increased the phosphorylation of ATF2, whereas overexpression of SOCS2 alleviated
this phenomenon. Taken together, our observations indicated that SOCS2 could
suppress myotube formation, act as an anti-regulator of mitochondria biogenesis
via inhibiting p38 MAPK signal pathway.
PMID- 24352702
TI - Meta-analysis of the association of glutathione S-transferase T1 null/presence
gene polymorphism with the risk of gastric carcinoma.
AB - A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene
polymorphism and an increased risk of developing gastric carcinoma is still
unclear and hotly debated. This investigation was performed to assess the
association of the GSTT1 null/presence gene polymorphism with the risk of gastric
carcinoma via a meta-analysis to increase sample size and statistical
significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine
Database) were searched on March 1, 2013, association reports were identified,
and eligible studies were recruited and synthesized. Fifty-two reports were found
to be suitable for this meta-analysis for the association of the GSTT1 null
genotype with gastric carcinoma risk. The results showed that there was a
significantly increased gastric carcinoma risk when the GSTT1 null genotype was
present in the overall population (OR 1.21, 95 % CI 1.11-1.32, P < 0.0001),
Caucasians (OR 1.25, 95 % CI 1.05-1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI
1.06-1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07-1.44, P = 0.005).
However, no statistically relevant association could be established for the
Indian ethnic group (OR 1.33, 95 % CI 0.94-1.90, P = 0.11). In conclusion, the
GSTT1 null genotype is associated with an increased gastric carcinoma risk in the
overall population, Caucasians, East-Asians, and Chinese.
PMID- 24352703
TI - Genomic organization, single nucleotide polymorphism and functional
characterization of natural killer enhancing factor (NKEF-A) in Miichthys miiuy.
AB - Peroxiredoxin (Prx) play vital parts in oxidative stress belonging to a cellular
antioxidant protein family. Natural killer enhancing factor (NKEF) is a member of
the Prx family, which is newly defined. In addition to antioxidant activity, NKEF
also can protect DNA from oxidative damage. In order to study immune defense
mechanism of NKEF in teleost, NKEF-A gene of miiuy croaker (Miichthys miiuy) was
cloned and characterized. The genomic organization containing one non-coding
exon, five coding exons and five introns, inclouding one intron located in 5'
terminal untranslated region. The full-length cDNA was 1235 bp, consisting of a
597 bp open reading frame coding for a protein of 198 amino acids. Sequence
comparison showed that the deduced amino acid sequence of miiuy croaker NKEF-A
had 71.4-90.3 % identity with those of mammal and teleost. Five single nucleotide
polymorphisms were detected by direct sequencing of eight samples from three
different populations. Phylogenetic analysis revealed that miiuy croaker NKEF-A
forms a cluster with other known teleost and mammalian NKEF-As. NKEF-A gene was
constitutively expressed in ten examined tissues, and expression level was up
regulated in liver, spleen and kidney after challenge with Vibrio anguillarum.
Finally, the NKEF-A was constructed and expressed in Escherichia coli. Then
purified recombinant pET-NKEF protein was used to produce the polyclonal antibody
and the polyclonal antibody against NKEF-A was tested by Western blot analysis.
These results indicate that NKEF may be involved in immune responses as well as
homeostatic processes in miiuy croaker.
PMID- 24352704
TI - The influence of nitrogen on the development and accumulation of protein bodies
in the developing endosperm of wheat caryopses.
AB - The aim of the present work was to reveal the histological changes of protein
bodies (PBs) in the developing wheat endosperm under nitrogen (N) treatment. For
this purpose, the development and accumulation of PBs in the dorsal and ventral
regions of wheat endosperm affected by N application at booting stage were
investigated using light microscopy and Image-Pro Plus 6.0 software. The
endosperm without N treatment contained many smaller PBs that were scattered in
endosperm cells in an unordered pattern, whereas the endosperm with N treatment
contained many larger PBs or aggregations that were concentrated in a certain
region of endosperm cells. The amount and relative areas of PBs in wheat
varieties cvs. Xumai 30 and Yangmai 13 were significantly increased by N
application. However, the cultivars differed with the degree of response to N
being cv. Xumai 30 > cv. Yangmai 13. These differences also varied with position
in the endosperm in the order ventral > dorsal region. The initiation of PBs
occurred 3 days earlier in N-treated endosperm than the control.
PMID- 24352705
TI - Correlations of C-reactive protein levels and erythrocyte sedimentation rates
with endoscopic activity indices in patients with ulcerative colitis.
AB - BACKGROUND: Accurate assessment of endoscopic severity is essential to the early
detection of relapses and treatment of patients with ulcerative colitis (UC).
However, the relationships between non-invasive biomarkers and invasive
endoscopic severity indices remain poorly understood. METHODS: A total of 722
endoscopies in 552 patients were evaluated in this study. Endoscopic activity was
assessed using five widely used endoscopic scoring systems: the Powell-Tuck
assessment, Mayo Endoscopic Score, modified Baron Score, Rachmilewitz Endoscopic
Activity Index, and Hanauer's Sigmoidoscopic Index. These five indices were
compared with two non-invasive biomarkers, erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP) levels. RESULTS: The Pearson's correlation
coefficients of CRP and ESR with endoscopic indices were r = 0.457 and 0.342 in
the Powell-Tuck assessment, r = 0.503 and r = 0.402 in the Mayo Endoscopic Score,
r = 0.507 and 0.408 in Hanauer's Sigmoidoscopic Index, r = 0.520 and 0.433 in the
modified Baron Score, and r = 0.523 and 0.435 in the Rachmilewitz Endoscopic
Activity Index. Sensitivity and specificity ranges for CRP and ESR were 50.5-53.3
% and 68.7-71.3 % and 85.1-87.2 % and 63.4-66.4 %, respectively, for the
detection of endoscopic remission using the five endoscopic indices. CONCLUSIONS:
CRP and ESR levels were modestly correlated with endoscopic activity indices in
UC patients. However, the low sensitivities for detecting endoscopic remission
suggest that CRP or ESR alone is not sufficient to reflect endoscopic severity
accurately.
PMID- 24352706
TI - Current issues in cereal crop biodiversity.
AB - The exploration, conservation, and use of agricultural biodiversity are essential
components of efficient transdisciplinary research for a sustainable agriculture
and food sector. Most recent advances on plant biotechnology and crop genomics
must be complemented with a holistic management of plant genetic resources. Plant
breeding programs aimed at improving agricultural productivity and food security
can benefit from the systematic exploitation and conservation of genetic
diversity to meet the demands of a growing population facing climate change. The
genetic diversity of staple small grains, including rice, maize, wheat, millets,
and more recently quinoa, have been surveyed to encourage utilization and
prioritization of areas for germplasm conservation. Geographic information system
technologies and spatial analysis are now being used as powerful tools to
elucidate genetic and ecological patterns in the distribution of cultivated and
wild species to establish coherent programs for the management of plant genetic
resources for food and agriculture.
PMID- 24352708
TI - Value of ultrasonography for detecting chronic injury of the lateral ligaments of
the ankle joint compared with ultrasonography findings.
AB - OBJECTIVE: The aim of this study was to assess the accuracy of ultrasonography in
the diagnosis of chronic lateral ankle ligament injury. METHODS: A total of 120
ankles in 120 patients with a clinical suspicion of chronic ankle ligament injury
were examined by ultrasonography by using a 5- to 17-MHz linear array transducer
before surgery. The results of ultrasonography were compared with the operative
findings. RESULTS: There were 18 sprains and 24 partial and 52 complete tears of
the anterior talofibular ligament (ATFL); 26 sprains, 27 partial and 12 complete
tears of the calcaneofibular ligament (CFL); and 1 complete tear of the posterior
talofibular ligament (PTFL) at arthroscopy and operation. Compared with operative
findings, the sensitivity, specificity and accuracy of ultrasonography were
98.9%, 96.2% and 84.2%, respectively, for injury of the ATFL and 93.8%, 90.9% and
83.3%, respectively, for injury of the CFL. The PTFL tear was identified by
ultrasonography. The accuracy of identification between acute-on-chronic and
subacute-chronic patients did not differ. The accuracies of diagnosing three
grades of ATFL injuries were almost the same as those of diagnosing CFL injuries.
CONCLUSION: Ultrasonography provides useful information for the evaluation of
patients presenting with chronic pain after ankle sprain. ADVANCES IN KNOWLEDGE:
Intraoperative findings are the reference standard. We demonstrated that
ultrasonography was highly sensitive and specific in detecting chronic lateral
ligments injury of the ankle joint.
PMID- 24352710
TI - Recommendations for treating hypertension: what are the right goals and purposes?
PMID- 24352711
TI - Aggregation behavior of nanodiamonds and their functionalized analogs in an
aqueous environment.
AB - The colloidal behavior of aqueous dispersions of detonation nanodiamonds (DNDs)
and carboxylated nanodiamonds (DND-COOH) which were synthesized via a microwave
process is presented. Both forms of DNDs were found to be relatively stable in
aqueous solutions, but aggregated rapidly in the presence of mono and divalent
salts. The critical coagulation concentration (CCC) values for DNDs and DND-COOH
were estimated to be between 8 and 10 mM for NaCl and 7 and 8 mM for MgCl2. In
general, the formation of carboxyl groups on the DND surface did not alter
colloidal behavior as dramatically as it is known to do for other nanocarbons
especially carbon nanotubes.
PMID- 24352707
TI - Effects of chronic HIV-1 Tat exposure in the CNS: heightened vulnerability of
males versus females to changes in cell numbers, synaptic integrity, and
behavior.
AB - HIV-associated damage to the central nervous system results in cognitive and
motor deficits. Anti-retroviral therapies reduce the severity of symptoms, yet
the proportion of patients affected has remained the same or increased. Although
approximately half of HIV-infected patients worldwide are women, the question of
whether biological sex influences outcomes of HIV infection has received little
attention. We explored this question for both behavioral and cellular/morphologic
endpoints, using a transgenic mouse that inducibly expresses HIV-1 Tat in the
brain. After 3 months of HIV-1 Tat exposure, both sexes showed similar reduced
open field ambulation. Male Tat(+) mice also showed reduced forelimb grip
strength and enhanced anxiety in a light-dark box assay. Tat(+) males did not
improve over 12 weeks of repeated rotarod testing, indicating a motor memory
deficit. Male mice also had more cellular deficits in the striatum. Neither sex
showed a change in volume or total neuron numbers. Both had equally reduced
oligodendroglial populations and equivalent microglial increases. However,
astrogliosis and microglial nitrosative stress were higher in males. Dendrites on
medium spiny neurons in male Tat(+) mice had fewer spines, and levels of
excitatory and inhibitory pre- and post-synaptic proteins were disrupted. Our
results predict sex as a determinant of HIV effects in brain. Increased
behavioral deficits in males correlated with glial activation and synaptic
damage, both of which are implicated in cognitive/motor impairments in patients.
Tat produced by residually infected cells despite antiretroviral therapy may be
an important determinant of the synaptodendritic instability and behavioral
deficits accompanying chronic infection.
PMID- 24352712
TI - Reversal of trauma-induced amnesia in mice by a thrombin receptor antagonist.
AB - Minimal traumatic brain injury (mTBI) is associated with the existence of
retrograde amnesia and microscopic bleeds containing activated coagulation
factors. In an mTBI model, we report that thrombin induces amnesia through its
receptor protease-activated receptor 1 (PAR-1). Thrombin activity was
significantly elevated (32 %, p < 0.05) 5 min following mTBI compared to
controls. Amnesia was assessed by the novel object recognition test in mTBI
animals and in animals injected intracerebroventricularly (ICV) with either
thrombin or a PAR-1 agonist 1 h after the acquisition phase. Saline-injected
controls had a preference index of over 0.3 while mTBI animals and those injected
with thrombin or the PAR-1 agonist spent equal time with both objects indicating
no recall of the object presented to them 24 h previously (p < 0.05). Co
injecting a PAR-1 antagonist (SCH79797) completely blocked the amnestic effects
of mTBI, thrombin, and the PAR-1 agonist. Long-term potentiation, measured in
hippocampal slices 24 h after mTBI, ICV thrombin or the PAR-1 agonist, was
significantly impaired and this effect was completely reversed by the PAR-1
antagonist. The results support a crucial role for PAR-1 in the generation of
amnesia following mTBI, revealing a novel therapeutic target for the cognitive
effects of brain trauma.
PMID- 24352713
TI - Association of innate immune single-nucleotide polymorphisms with the
electroencephalogram during desflurane general anaesthesia.
AB - The electroencephalogram (EEG) records the electrical activity of the brain and
enables effects of anaesthetic drugs on brain functioning to be monitored.
Identification of genes contributing to EEG variability during anaesthesia is
important to the clinical application of anaesthesia monitoring and may provide
an avenue to identify molecular mechanisms underlying the generation and
regulation of brain oscillations. Central immune signalling can impact neuronal
activity in the brain and accumulating evidence suggests an important role for
cytokines as neuronal modulators. We tested 21 single-nucleotide polymorphisms
(SNPs) in immune-related genes for associations with three anaesthesia-induced
EEG patterns; spindle amplitude, delta power and alpha power, during general
anaesthesia with desflurane in 111 patients undergoing general, gynaecological or
orthopaedic surgery. Wide inter-patient variability was observed for all EEG
variables. MYD88 rs6853 (p = 6.7 * 10(-4)) and IL-1beta rs1143627 in conjunction
with rs6853 (p = 1.5 * 10(-3)) were associated with spindle amplitude, and IL-10
rs1800896 was associated with delta power (p = 1.3 * 10(-2)) suggesting
involvement of cytokine signalling in modulation of EEG patterns during
desflurane anaesthesia. BDNF rs6265 was associated with alpha power (p = 3.9 *
10(-3)), suggesting differences in neuronal plasticity might also influence EEG
patterns during desflurane anaesthesia. This is the first study we are aware of
that has investigated genetic polymorphisms that may influence the EEG during
general anaesthesia.
PMID- 24352715
TI - The shape of modern tree reconstruction methods.
PMID- 24352714
TI - Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1: a meaningful and
independent marker to predict stroke in the Chinese population.
AB - Label-free liquid chromatography-mass spectrometry (LC-MS) quantification methods
have been described to determine serum proteins biomarkers in many diseases.
Thus, the purpose of this study was to investigate the serum proteins biomarkers
in the Chinese patients with acute ischemic stroke (AIS). In the study period,
sera from 40 AIS patients and 40 normal cases were selected for screening study.
Immunoaffinity subtraction was used to deplete the top most abundant serum
proteins; the remaining serum proteins were subjected to trypsin digestion and
analyzed in triplicate by label-free LC-MS/MS. The selected protein associations
with disease risk were further evaluated by enzyme-linked immunosorbent assay
(ELISA) testing of the remaining stroke cases and controls. Its value for
biomarkers diagnosis was appreciated through receiver operating curve (ROC).
Patients versus control levels differences were suggested for 19 proteins
(nominal P < 0.05) for stroke, with three proteins having a false discovery rate
<0.05. The association of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase
1 (SHIP-1) with stroke (P < 0.001) was confirmed using ELISA in replication
studies. Based on the ROC curve, the optimal cut-off value of serum SHIP-1 levels
for diagnosis of stroke was projected to be 1,550 pg/ml, which yielded a
sensitivity of 77.5% and a specificity of 88.3%. In multivariate analysis, there
was an increased risk of AIS associated with SHIP-1 levels >= 1,550 pg/ml (OR
4.28, 95% CI: 1.97-8.96) after adjusting for possible confounders. CONCLUSION:
The discovery and replication studies presented here show SHIP-1 to be a risk
marker for AIS in the Chinese population, which appears to be a novel finding.
PMID- 24352716
TI - Resolution of sleepiness and fatigue: a comparison of bupropion and selective
serotonin reuptake inhibitors in subjects with major depressive disorder
achieving remission at doses approved in the European Union.
AB - Unlike selective serotonin reuptake inhibitors (SSRIs), bupropion may be
classified as a dual noradrenaline and dopamine reuptake inhibitor, a difference
with potential implications for the treatment of residual sleepiness and fatigue
in major depressive disorder (MDD). Post-hoc analysis of subjects with remitted
MDD was performed on data pooled from six double-blind, randomized trials
comparing the European Union (EU)-approved dose of <=300 mg/day bupropion with
SSRIs (sertraline, paroxetine or escitalopram) for the resolution of sleepiness
and fatigue. Hypersomnia score was defined as the sum of scores of the Hamilton
Depression Rating Scale (HDRS) items 22, 23, and 24; fatigue score as HDRS item
13 score; and remission as HDRS-17<=7. Similar proportions of bupropion- and SSRI
treated subjects achieved remission at study endpoint (169/343, 49.3% vs 324/656,
49.4%; last observation carried forward (LOCF), p=0.45). Fewer bupropion-treated
remitters had residual symptoms of sleepiness (32/169, 18.9% vs 104/324, 32.1%;
p<0.01) and fatigue (33/169, 19.5% vs 98/324, 30.2%; p<0.05). Bupropion-treated
remitters also showed greater improvement (mean change from baseline) in
sleepiness (p<0.05) and fatigue scores (p<0.01) at endpoint: benefits were
evident from week 2 for sleepiness (p<0.01) and week 4 for fatigue (p<0.01).
Bupropion treatment at the EU-approved dose of <=300 mg/day may offer advantages
over SSRIs in the resolution of sleepiness and fatigue in remitted MDD patients.
PMID- 24352719
TI - Organotherapy.
PMID- 24352720
TI - An unusual pigmented lesion: what is your diagnosis?
PMID- 24352721
TI - Defying the odds: Dr Ricky Kanee Schachter.
PMID- 24352722
TI - What's in a name?: Goeckerman therapy.
PMID- 24352723
TI - The importance of being fragrant.
PMID- 24352724
TI - There's no place like home: dermatologic toponyms from the United States.
PMID- 24352725
TI - IgG4-related skin disease.
PMID- 24352726
TI - IgG4-related skin disease--reply.
PMID- 24352728
TI - Squamous cell carcinoma.
PMID- 24352729
TI - Dendrimer-carbon nanotube layer-by-layer film as an efficient host matrix for
electrogeneration of PtCo electrocatalysts.
AB - In this paper we demonstrate that layer-by-layer (LbL) films of polyamidoamine
(PAMAM) dendrimers and single-walled carbon nanotubes (SWCNTs) are efficient for
controlling the morphology of electrogenerated cobalt (Co) and the platinum
cobalt (PtCo) alloy. While Co grew to the micrometer scale and poorly covered the
ITO substrate, with the LbL matrix it was kept in the nanoscale regime and
provided full substrate coverage. Pt-decorated Co nanoparticles were then
generated by applying a single potential pulse in a solution containing
simultaneously Co and Pt ions. Segregation of Pt and Co deposits was observed in
field emission gun (FEG) images, but the PtCo alloy was probably formed to some
extent according to X-ray diffraction analysis. The PtCo-LbL hybrid exhibited
superior catalytic activity toward H2O2 reduction compared to the Pt-modified LbL
film, which opens new prospects for applications in biosensing and fuel cells.
PMID- 24352730
TI - Development of an improved phenylacetaldehyde reductase mutant by an efficient
selection procedure.
AB - Chiral alcohols are valuable as diverse chemicals and synthetic intermediate
materials. Phenylacetaldehyde reductase (PAR) is an enzyme that converts a wide
variety of ketones into chiral alcohols with high optical purity. When an alcohol
such as 2-propanol is used as a hydrogen donor, PAR itself will also mediate the
regeneration of the coenzyme NADH in situ. Perceiving a capacity for improvement,
we sought to develop a PAR that is able to convert higher concentrations of
substrates in the presence of high concentrations of 2-propanol. The selection
procedure for mutants was re-examined and a procedure able to select an effective
amino acid substitution was established. Two advantageous amino acid
substitutions were successfully selected using the procedure. When high
concentration substrate conversion reaction was subjected with a mutant that
integrated both the two amino acid substitutions, near-complete conversions of m
chlorophenacyl chloride (m-CPC) (2.1 mmol/ml) and ethyl 4-chloro-3-oxobutanoate
(ECOB) (1.9 mmol/ml) were achieved.
PMID- 24352731
TI - Transformation of saturated nitrogen-containing heterocyclic compounds by
microorganisms.
AB - The saturated nitrogen-containing heterocyclic compounds include many drugs and
compounds that may be used as synthons for the synthesis of other
pharmacologically active substances. The need for new derivatives of saturated
nitrogen-containing heterocycles for organic synthesis, biotechnology and the
pharmaceutical industry, including optically active derivatives, has increased
interest in microbial synthesis. This review provides an overview of microbial
technologies that can be valuable to produce new derivatives of saturated
nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-,
regio- and enantioselectivity of microbial processes can be indispensable for the
synthesis of new compounds. Microbial processes carried out with fungi, including
Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum,
Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including
Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many
substrates efficiently. Among the biological activities of saturated nitrogen
containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive
and anti-HIV activities; some derivatives are effective for the treatment and
prevention of malaria and trypanosomiasis, and others are potent glycosidase
inhibitors.
PMID- 24352732
TI - Microbial alkyl- and aryl-sulfatases: mechanism, occurrence, screening and
stereoselectivities.
AB - This review gives an overview on the occurrence of sulfatases in Prokaryota,
Eukaryota and Archaea. The mechanism of enzymes acting with retention or
inversion of configuration during sulfate ester hydrolysis is discussed taking
two complementary examples. Methods for the discovery of novel alkyl sulfatases
are described by way of sequence-based search and enzyme induction. A
comprehensive list of organisms with their respective substrate scope regarding
prim- and sec-alkyl sulfate esters allows to assess the capabilities and
limitations of various biocatalysts employed as whole cell systems or as purified
enzymes with respect to their activities and enantioselectivities. Methods for
immobilization and selectivity enhancement by addition of metal ions or organic
(co)solvents are summarised.
PMID- 24352733
TI - Overexpression of a type II 3-dehydroquinate dehydratase enhances the
biotransformation of quinate to 3-dehydroshikimate in Gluconobacter oxydans.
AB - Shikimate and 3-dehydroshikimate are useful chemical intermediates for the
synthesis of various compounds, including the antiviral drug oseltamivir. Here,
we show an almost stoichiometric biotransformation of quinate to 3
dehydroshikimate by an engineered Gluconobacter oxydans strain. Even under pH
control, 3-dehydroshikimate was barely detected during the growth of the wild
type G. oxydans strain NBRC3244 on the medium containing quinate, suggesting that
the activity of 3-dehydroquinate dehydratase (DHQase) is the rate-limiting step.
To identify the gene encoding G. oxydans DHQase, we overexpressed the gox0437
gene from the G. oxydans strain ATCC621H, which is homologous to the aroQ gene
for type II DHQase, in Escherichia coli and detected high DHQase activity in cell
free extracts. We identified the aroQ gene in a draft genome sequence of G.
oxydans NBRC3244 and constructed G. oxydans NBRC3244 strains harboring plasmids
containing aroQ and different types of promoters. All recombinant G. oxydans
strains produced a significant amount of 3-dehydroshikimate from quinate, and
differences between promoters affected 3-dehydroshikimate production levels with
little statistical significance. By using the recombinant NBRC3244 strain
harboring aroQ driven by the lac promoter, a sequential pH adjustment for each
step of the biotransformation was determined to be crucial because 3
dehydroshikimate production was enhanced. Under optimal conditions with a shift
in pH, the strain could efficiently produce a nearly equimolar amount of 3
dehydroshikimate from quinate. In the present study, one of the important steps
to convert quinate to shikimate by fermenting G. oxydans cells was investigated.
PMID- 24352734
TI - L-Amino acid oxidases from microbial sources: types, properties, functions, and
applications.
AB - L-Amino acid oxidases (LAAOs), which catalyze the stereospecific oxidative
deamination of L-amino acids to alpha-keto acids and ammonia, are flavin adenine
dinucleotide-containing homodimeric proteins. L-Amino acid oxidases are widely
distributed in diverse organisms and have a range of properties. Because
expressing LAAOs as recombinant proteins in heterologous hosts is difficult,
their biotechnological applications have not been thoroughly advanced. LAAOs are
thought to contribute to amino acid catabolism, enhance iron acquisition, display
antimicrobial activity, and catalyze keto acid production, among other roles.
Here, we review the types, properties, structures, biological functions,
heterologous expression, and applications of LAAOs obtained from microbial
sources. We expect this review to increase interest in LAAO studies.
PMID- 24352735
TI - Production of D-arabitol from raw glycerol by Candida quercitrusa.
AB - To promote the effective use of raw glycerol (a by-product of biodiesel
production), 110 yeast strains that produce D-arabitol from glycerol were
isolated from environmental samples. Among them, strain 17-2A was an effective D
arabitol producer in the presence of 250 g/l glycerol and was identified as
Candida quercitrusa based on morphological, physicochemical, and phylogenetic
analyses. C. quercitrusa type strain NBRC1022 produced the greatest quantity of D
arabitol (41.7 g/l) when the ability to produce D-arabitol from raw glycerol was
compared among C. quercitrusa 17-2A and its phylogenetically related strains in
flask culture. Under optimized culture conditions, strain NBRC1022 produced D
arabitol at a concentration of 58.2 g/l after a 7-day cultivation in 250 g/l
glycerol, 6 g/l yeast extract, and 2 g/l CaCl2. The culture conditions were
further investigated with raw glycerol using a jar fermenter; the concentration
of D-arabitol reached 67.1 g/l after 7 days and 85.1 g/l after 10 days,
respectively, which corresponded to 0.40 g/g of glycerol. To our knowledge, the
present D-arabitol yield from glycerol is higher than reported previously using
microbial production.
PMID- 24352736
TI - Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery
calcification in Japanese men in Japan and white men in the USA: population based
prospective cohort study.
AB - OBJECTIVE: To determine whether serum concentrations of long chain n-3
polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the
incidence rate of coronary artery calcification (CAC) between Japanese men in
Japan and white men in the USA. METHODS: In a population based, prospective
cohort study, 214 Japanese men and 152 white men aged 40-49 years at baseline
(2002-2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007
2010. Among these, 175 Japanese men and 113 white men participated in the follow
up exam. Incident cases were defined as participants with CCS>=10 at follow-up. A
relative risk regression analysis was used to model the incidence rate ratio
between the Japanese and white men. The incidence rate ratio was first adjusted
for potential confounders at baseline and then further adjusted for serum
LCn3PUFAs at baseline. RESULTS: Mean (SD) serum percentage of LCn3PUFA was >100%
higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79),
respectively, p<0.01). Japanese men had a significantly lower incidence rate of
CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01).
The incidence rate ratio of CAC taking follow-up time into account between
Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting
for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes,
and other potential confounders, the ratio remained significant (0.262, 95% CI
0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the
ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572;
p=0.18). CONCLUSIONS: LCn3PUFAs significantly contributed to the difference in
the incidence of CAC between Japanese and white men.
PMID- 24352737
TI - Drug-coated balloons in the treatment of small vessel disease.
PMID- 24352739
TI - Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre
stage.
AB - An essential aspect of normal brain function is the bidirectional interaction and
communication between neurons and neighbouring glial cells. To this end, the
brain has evolved ligand-receptor partnerships that facilitate crosstalk between
different cell types. The chemokine, fractalkine (FKN), is expressed on neuronal
cells, and its receptor, CX(3)CR1, is predominantly expressed on microglia. This
review focuses on several important functional roles for FKN/CX(3)CR1 in both
health and disease of the central nervous system. It has been posited that FKN is
involved in microglial infiltration of the brain during development. Microglia,
in turn, are implicated in the developmental synaptic pruning that occurs during
brain maturation. The abundance of FKN on mature hippocampal neurons suggests a
homeostatic non-inflammatory role in mechanisms of learning and memory. There is
substantial evidence describing a role for FKN in hippocampal synaptic
plasticity. FKN, on the one hand, appears to prevent excess microglial activation
in the absence of injury while promoting activation of microglia and astrocytes
during inflammatory episodes. Thus, FKN appears to be neuroprotective in some
settings, whereas it contributes to neuronal damage in others. Many progressive
neuroinflammatory disorders that are associated with increased microglial
activation, such as Alzheimer's disease, show disruption of the FKN/CX(3)CR1
communication system. Thus, targeting CX(3)CR1 receptor hyperactivation with
specific antagonists in such neuroinflammatory conditions may eventually lead to
novel neurotherapeutics.
PMID- 24352741
TI - Protein-directed synthesis of pH-responsive red fluorescent copper nanoclusters
and their applications in cellular imaging and catalysis.
AB - The development of functional copper nanoclusters (Cu NCs) is becoming
increasingly widespread in consumer technologies due to their applications in
cellular imaging and catalysis. Herein, we report a simple protein-directed
synthesis of stable, water-soluble and fluorescent Cu NCs, using BSA as the
stabilising agent. Meanwhile, in this study, hydrazine hydrate (N2H4.2H2O) was
used as the reducing agent. N2H4.2H2O was a mild reducing agent suggesting that
all processes could be operated at room temperature. The as-prepared Cu NCs
showed red fluorescence with a peaking center at 620 nm (quantum yield 4.1%). The
fluorescence of the as-prepared BSA-Cu NCs was responsive to pH in that the
intensity of fluorescence increased rapidly by decreasing the pH from 12 to 6.
Besides, with an arresting set of features including water-dispersibility, red
fluorescence, good biocompatibility, surface-bioactivity and small size, the
resultant BSA-Cu NCs could be used as probes for cellular imaging and catalysis.
In this study, CAL-27 cells and the reaction of oxidation of styrene are used as
models to achieve fluorescence imaging and elucidate the catalytic activity of
the as-prepared BSA-Cu NCs.
PMID- 24352740
TI - Rheb and mammalian target of rapamycin in mitochondrial homoeostasis.
AB - Mitochondrial dysfunction has been associated with various diseases, such as
cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is
achieved by mechanisms that adapt the number of mitochondria to that required for
energy production and for the supply of metabolic intermediates necessary to
sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are
in place to remove malfunctioning mitochondria. In the cytoplasm, the protein
complex mTORC1 couples growth-promoting signals with anabolic processes, in which
mitochondria play an essential role. Here, we review the involvement of mTORC1
and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of
mTORC1 affect the glycolytic flux and the rate of mitophagy, and include
regulation of the transcription factors HIF1alpha and YY1/PGC-1alpha. We also
discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen
species signalling to adapt metabolic processes, and highlight how mTORC1
signalling is integrated with the unfolded protein response in mitochondria,
which in Caenorhabditis elegans is mediated via transcription factors such as DVE
1/UBL-5 and ATFS-1.
PMID- 24352742
TI - Disease progression in autosomal dominant cone-rod dystrophy caused by a novel
mutation (D100G) in the GUCA1A gene.
AB - PURPOSE: To document longitudinal fundus autofluorescence (FAF) and
electroretinogram (ERG) findings in a family with cone-rod dystrophy (CRD) caused
by a novel missense mutation (D100G) in the GUCA1A gene. METHODS: Observational
case series. RESULTS: Three family members 26-49 years old underwent complete
clinical examinations. In all patients, funduscopic findings showed intraretinal
pigment migration, loss of neurosensory retinal pigment epithelium, and macular
atrophy. FAF imaging revealed the presence of a progressive hyperautofluorescent
ring around a hypoautofluorescent center corresponding to macular atrophy. Full
field ERGs showed a more severe loss of cone than rod function in each patient.
Thirty-hertz flicker responses fell far below normal limits. Longitudinal FAF and
ERG findings in one patient suggested progressive CRD. Two more advanced patients
exhibited reduced rod response consistent with disease stage. Direct sequencing
of the GUCA1A gene revealed a new missense mutation, p.Asp100Gly (D100G), in each
patient. CONCLUSION: Patients with autosomal dominant CRD caused by a D100G
mutation in GUCA1A exhibit progressive vision loss early within the first decade
of life identifiable by distinct ERG characteristics and subsequent genetic
testing.
PMID- 24352743
TI - [Professional image of anesthetists in the general public. Influence of provision
of information and previous experience with the discipline].
AB - BACKGROUND: The profession of the anesthetist in Germany includes the disciplines
anesthesia, intensive care, emergency and pain medicine. Despite the versatility
and competence of the profession, patients do not appear to have recognized
anesthesiology as a medical discipline or anesthetists as medical doctors. AIM:
This study was conducted with the aim of estimating how previous experience and
information gathered before contact with the anesthetist for premedication have
influenced and changed the perception of patients with regards to the
professional fields and the characteristics of anesthetists. MATERIAL AND
METHODS: A total of 3,950 patients from 3 German hospitals were asked to answer a
questionnaire handed out by the assistance nurse in the premedication area prior
to the medical consultation with the duty anesthetist. The questions involved the
patient perception of the discipline, the characteristics of anesthetists and
also evaluated the patient previous experience and provision of information.
According to the answers 1,753 patients were considered eligible for the study
and were categorized into subgroups I-IV (group I interested and experienced with
operations, group II interested but inexperienced, group III uninterested but
experienced and group IV neither interested nor experienced) for statistical
analysis. RESULTS: Of the respondents 56.2 % had obtained previous information
from a general practitioner followed by acquaintances (21.4 %) and the internet
(19.9 %), which significantly differed with age. Interested and experienced
patients showed the best perception of the profession. Often, the knowledge of
interested and uninterested persons did not significantly differ. Interested
patients and those with experience of anesthesiology had the best knowledge of
anesthesiology. Performing anesthesia was most often identified by all groups
(50.9-95.3 %) as a function of anesthetists while the other professional fields
were recognized correctly by only 5.8-26.6 %. Depending on the group 41.0-84.4 %
regarded anesthetists as medical doctors. Only 15.0-78.3 % of other attributes
were associated with anesthetists. CONCLUSION: Unfortunately, the perception of
patients on the versatility and characteristics of anesthetists are poorly
developed. However, the knowledge differs significantly depending on previous
experience and gathered information. Interestingly patients with previous
experience mostly showed better knowledge compared to interested patients.
Results suggest that personal interaction, patient-physician communication in
general and improved collaboration between general practitioners and anesthetists
are the key elements for better patient knowledge, which could lead to increased
patient satisfaction.
PMID- 24352744
TI - [Comments on: cooling and temperature management after cardiac arrest].
PMID- 24352745
TI - The impact of baseline [-2]proPSA-related indices on the prediction of
pathological reclassification at 1 year during active surveillance for low-risk
prostate cancer: the Japanese multicenter study cohort.
AB - PURPOSE: Active surveillance (AS) is one potential solution to avoiding the
overtreatment of favorable prostate cancer. By handling the AS strategy more
safely, tumor aggressiveness may be evaluated more accurately. The aim of the
present study was to evaluate the predictive impact of baseline prostate-specific
antigen (PSA) isoform [-2]proPSA (p2PSA)-related indices on the pathological
reclassification at 1 year during an AS program. METHODS: Between 2002 and 2003,
134 males diagnosed with low-risk prostate cancer were registered in the Japanese
multicenter study cohort as candidates for AS, and 118 (88 %) males actually
proceeded to AS. Of the 118 patients, the 67 that underwent protocol biopsy at 1
year after beginning AS were enrolled in the present study. The predictive
significance of various baseline clinicopathological features and p2PSA-related
indices on pathological reclassification at 1 year after beginning AS were
investigated. RESULTS: The pathological reclassification rate was 37.3 %.
According to the univariate analysis, prostate volume (p = 0.049), number of
biopsy cores (p = 0.047), percentage of positive biopsy cores (p = 0.023), p2PSA
to free PSA ratio (%p2PSA) (p = 0.003) and prostate health index (phi) (p =
0.010) at baseline were significantly different between the reclassification and
non-reclassification groups. By multivariate logistic regression analysis,
baseline %p2PSA (p = 0.008) and phi (p = 0.008) were the only independent
predictive factors for pathological upgrade at 1 year after AS commencement.
CONCLUSIONS: Baseline %p2PSA and phi may predict the pathological
reclassification at 1 year after starting AS, which could be due to the under
detection of clinically significant prostate cancer at AS enrollment.
PMID- 24352746
TI - Lifestyle modification parallels to sleeve success.
AB - BACKGROUND: The role of laparoscopic sleeve gastrectomy (LSG) has increased over
the past 10 years. We present our results of patients who were 5 years out from
surgery with regard to safety and long-term efficacy. METHODS: Retrospective
analysis was carried out from prospectively collected data of patients who
underwent LSG for morbid obesity. Bariatric Analysis and Reporting Outcome System
(BAROS) and Food Tolerance Scores (FTS) were assessed. At 5 years, two lifestyle
modification questions (regarding nutrition habits and physical fitness) were
separately assessed. RESULTS: One hundred fourteen patients underwent LSG and
were available for postoperative visits. Mean excess weight loss (EWL) was >65%
during the initial 3 years and declined to 45.3% in 5 years. Of the patients,
71.92% did not reach 50% EWL at 60 months and were considered objective failures.
BAROS and FTS scores were 7.15 and 4.32, and 23.5 and 22.5 at 30 and 60 months,
respectively. Analyzing the 32 patients with EWL >50% in the 5-year group, 26
(81.25%) of them had scored >=0.5 on the two lifestyle modification questions
compared with 6 (18.75%) that scored <0.5 (P < 0.001). CONCLUSION: LSG is an
effective bariatric surgical procedure with significant long-term (5 year) weight
loss, resolution of comorbid medical conditions and significant improvement in
the quality of life. The basis for this success, which must be always emphasized
preoperatively by the bariatric team, is knowledge and implementation of better
nutritional habits and increasing physical fitness or, in other words, in
significant lifestyle modification.
PMID- 24352747
TI - Perceptions of weight loss experience between African-Americans and Caucasians: a
pilot study.
AB - BACKGROUND: Obesity is a growing epidemic in the USA, which leads to
comorbidities associated with diseases such as hypertension, diabetes, sleep
apnea, cardiovascular disease, osteoarthritis, cancer, gallbladder disease, and
dyslipidemia. The purpose of this study is to identify perceptions of weight loss
experience between African-American (AA) and Caucasian patients undergoing
bariatric surgery. METHODS: A convenience sample of 31 patients participated in
this study from May to June 2013. The sample size consisted of 16 AA and 15
Caucasians from two fully accredited and licensed bariatric clinics in
metropolitan Detroit. RESULTS: The sample (N = 31) consists of eligible AA and
Caucasian presurgical bariatric patients on their first preoperative appointment.
Snacking and sexual satisfaction showed a significant difference (p < 0.05),
lower amongst Caucasians than amongst the AA. The results revealed that salary
within the AA population was significantly lower than that of the Caucasians,
especially in the $26.000 to $36,000 category as well as in the over $40,000
category. CONCLUSIONS: The discrepancy widened as the variables of snacks, sexual
satisfaction, and salary revealed a significant difference for Caucasians than
AA. It is prudent that health-care providers become part of the obesity
management solution by examining these variables when planning weight loss
interventions.
PMID- 24352748
TI - Laparoscopic gastric bypass vs. sleeve gastrectomy in the super obese patient:
early outcomes of an observational study.
AB - BACKGROUND: Super obesity [body mass index (BMI) > 50 kg/m2] can yield to higher
morbidity/mortality in bariatric surgery, this could be related to patient's
characteristics and/or surgeon's experience. In morbid obesity, both techniques
proved to have a positive impact and sometimes comparable outcomes during the
first 2 years. This has not been clearly analyzed in the super obese patient.
METHODS: Retrospective study comparing the records of 77 consecutive super obese
patients (BMI: 50-59.9 kg/m2) submitted to either laparoscopic gastric bypass
(LGBP, n = 32) or laparoscopic sleeve gastrectomy (LSG, n = 45) between 2010 and
2012 at a single institution. The primary objective was to analyze baseline
demographics, comorbidities, operative outcomes, and early complications (<30
days). Secondarily, weight loss [BMI and % excess weight loss (%EWL)] was also
described and compared during the first year. RESULTS: Female sex comprised 72.7
% of all cases. Both groups had comparable BMI (52.7 +/- 2.1 kg/m2 for LGBP vs.
53.87 +/- 2.8 kg/m2 for LSG; p = 0.087) and homogeneous baseline characteristics.
Operative time was lower for the LSG group (113.1 +/- 35.3 vs. 186.9 +/- 39 min
for LGBP; p <= 0.001). Overall, early complications were observed in 16.8% of
patients (LGBP 9% vs. LSG 22%; p = 0.217). There were four major complications
(two in each group), with two reinterventions. Weight loss (%EWL) at 6, 9, and 12
months was significantly higher in the LGBP group (51.6 +/- 12.9%, 56.5 +/- 13%,
63.9 +/- 13.3%, respectively) than in the LSG group (40 +/- 12.8%, 45.1 +/-
15.5%, 43.9 +/- 10.4%, respectively). CONCLUSIONS: Just like in morbid obesity,
LGBP and LSG are effective and safe procedures in super obese patients. LGBP had
better weight loss at 1 year.
PMID- 24352749
TI - Laparoscopic total gastrectomy with Roux-y esophagojejunostomy for chronic
gastric fistula after laparoscopic sleeve gastrectomy.
AB - Laparoscopic sleeve gastrectomy is a restrictive operation with hormonal elements
that is rapidly gaining popularity. The most feared complication of the procedure
is a staple line leak. The treatment of staple line leakage depends on timing and
clinical and anatomical considerations. If leakage persists and transforms into a
chronic fistula, a definitive surgical procedure is required. In cases where the
fistula originates close to the esophagogastric junction, the surgical
possibilities are limited and one treatment option is total gastrectomy with
esophagojejunal anastomosis. We report a case series of four patients with
chronic fistulae, who failed conservative treatment and required total
gastrectomy. Their average length of hospital stay was 8.7 days (range, 5-15
days), without conversions, leaks, or other complications. In experienced hands,
total gastrectomy is feasible by laparoscopic techniques and should be performed
soon after the fistula is established.
PMID- 24352751
TI - Cranial neuropathies in granulomatosis with polyangiitis (Wegener's): a case
based review.
AB - The purpose of this case-based review is to highlight cranial nerve involvement
in granulomatosis with polyangiitis (Wegener's). In this disease, cranial nerve
involvement may be less frequent than other neurological manifestations, but
often goes unrecognized by physicians as a sign of the disease, and its
prevalence and importance is likely underestimated. Awareness of this aspect of
the disease is necessary to make the proper diagnosis rapidly, as it can be a
major feature of a patient's presentation. We also briefly discuss the known
pathogenic mechanisms, which could be important when selecting the best
therapeutic option.
PMID- 24352752
TI - Comparison of dry needling and physiotherapy in treatment of myofascial pain
syndrome.
AB - To compare the effects of dry needling and physiotherapy in treatment of
myofascial pain syndrome, a randomized controlled trial was performed on 28
patients with myofascial pain syndrome (MPS) of upper trapezius muscle in the
Physical Medicine and Rehabilitation Center of Shohadaye Tajrish Hospital from
April 2009 to April 2010. After matching the age, sex, duration of symptoms, pain
severity, and quality of life measures, subjects were randomly assigned into two
subgroups of case (dry needling) and control (physiotherapy). One week and 1
month after receiving standard therapeutic modalities, outcomes and intragroup
and intergroup changes in pain severity, pressure pain of trigger point (TP), and
quality of life measures were evaluated and compared. After 1 month, both the
physiotherapy and dry needling groups had decreased resting, night, and activity
pain levels (p<0.05). Pressure pain threshold of TP and some scores of quality of
life (SF-36) were improved (p<0.05). Overall results were similar in both groups.
It seems that both physiotherapy modalities and dry needling have equal effect on
myofascial pain of the upper trapezius muscle.
PMID- 24352753
TI - Plaque morphea with neurological involvement-an extraordinary uncommon
presentation.
AB - Localized scleroderma is traditionally considered to be limited to the skin,
subcutaneous tissue, underlying bone, and in the craniofacial subtype, also
nervous system involvement. However, recent studies have also described other
systemic manifestations in these patients. Despite many reports of neurological
involvement in patients with the craniofacial linear localized scleroderma, it is
extremely rare in patients with the other subtypes of localized scleroderma.
Here, we report an extraordinary case of localized scleroderma en plaque (classic
morphea), located to the upper trunk and neck, associated with neurological
manifestations presented as seizures. Magnetic resonance imaging of the brain
showed focal lesions on the contralateral side to the skin involvement. This case
is extremely relevant not only due to its rarity, but also because it supports
the idea that the pathogenesis of the localized scleroderma is related to a
systemic autoimmune process.
PMID- 24352754
TI - Kimura's disease or IgG4-related disease? A case-based review.
AB - Kimura's disease usually presents with benign painless soft tissue swelling
around the head and neck areas with eosinophilia and high immunoglobulin E (IgE)
levels. IgG4-related disease is characterized by fibrosis and sclerosis of the
involved organs, with infiltration of IgG4-positive plasma cells. There are some
similar clinical manifestations of these two diseases, with eosinophilia or high
IgE levels often found in patients with IgG4-related disease. However, the
relation between these two diseases is not well known. We report a 23-year-old
man who had multiple neck lumps for longer than 1 year. He had remarkable
eosinophilia and elevated serum IgE levels. Biopsy of his lymph nodes suggested
the diagnosis of both Kimura's disease and IgG4-related disease. In this article,
we discuss the relationship between Kimura's disease and IgG4-related disease. We
also suggest a possible model ("allergen-specific immunotherapy") to illustrate
our view that an increase in IgG4-positive plasma cells is an epiphenomenon of
Kimura's disease.
PMID- 24352756
TI - Negative pressure wound therapy for managementof the surgical incision in
orthopaedic surgery: A review of evidence and mechanisms for an emerging
indication.
AB - OBJECTIVES: The period of post-operative treatment before surgical wounds are
completely closed remains a key window, during which one can apply new
technologies that can minimise complications. One such technology is the use of
negative pressure wound therapy to manage and accelerate healing of the closed
incisional wound (incisional NPWT). METHODS: We undertook a literature review of
this emerging indication to identify evidence within orthopaedic surgery and
other surgical disciplines. Literature that supports our current understanding of
the mechanisms of action was also reviewed in detail. RESULTS: A total of 33
publications were identified, including nine clinical study reports from
orthopaedic surgery; four from cardiothoracic surgery and 12 from studies in
abdominal, plastic and vascular disciplines. Most papers (26 of 33) had been
published within the past three years. Thus far two randomised controlled trials
one in orthopaedic and one in cardiothoracic surgery - show evidence of reduced
incidence of wound healing complications after between three and five days of
post-operative NPWT of two- and four-fold, respectively. Investigations show that
reduction in haematoma and seroma, accelerated wound healing and increased
clearance of oedema are significant mechanisms of action. CONCLUSIONS: There is a
rapidly emerging literature on the effect of NPWT on the closed incision.
Initiated and confirmed first with a randomised controlled trial in orthopaedic
trauma surgery, studies in abdominal, plastic and vascular surgery with high
rates of complications have been reported recently. The evidence from single-use
NPWT devices is accumulating. There are no large randomised studies yet in
reconstructive joint replacement. Cite this article: Bone Joint Res 2013;2:276
84.
PMID- 24352757
TI - Investigation of biological factors influencing the placental mRNA profile in
maternal plasma.
AB - OBJECTIVE: Circulating placental-derived RNA is useful for noninvasive prenatal
investigation. However, in addition to placental gene expression, there are
limited investigations on other biological parameters that may affect the
circulating placental RNA profile. In this study, we explored two of these
potential parameters. METHODS: We first demonstrated the existence of such
biological parameters by comparing the relative levels of a panel of placental
derived transcripts between the placentas and maternal plasma by digital PCRs. We
then compared the post-delivery clearance of the transcripts by serial plasma
samples collected from pregnant women after delivery. We also studied the
placental in vivo localization of the transcripts by in situ hybridization.
RESULTS: There was an imperfect correlation of the transcript levels between the
placentas and maternal plasma, with placenta-specific 4 (PLAC4) mRNA showing the
largest discrepancy. Although PLAC4 mRNA showed a similar clearance half-life
with other transcripts, we observed a preferential localization of PLAC4 mRNA
around the villous surface. We speculated that this phenomenon might play a role
in favoring the release of PLAC4 mRNA molecules into maternal plasma. CONCLUSION:
We revealed that in addition to expression levels in the placenta, other
biological factors might interplay to determine the maternal plasma profile of
placental-derived RNAs.
PMID- 24352758
TI - Regulation effect of polysaccharides from Pleurotus tuber-regium (Fr.) on the
immune activity of mice macrophages.
AB - Pleurotus tuber-regium (Fr.) is widely consumed as a nutritious food due to its
multiple health effects, especially immune function. This study was aimed at
investigating its immune activity using the mice peritoneal macrophage model. Two
polysaccharides, water and alkaline extraction of polysaccharides (W-PTR and A
PTR), from P. tuber-regium were used to test their immune functions and compare
their possible activity differences. Results showed that both W-PTR and A-PTR
showed a significant enhancement effect on the macrophage phagocytosis, and could
activate the related enzymes, such as ATPases, lysozyme, and LDH, which are
responsible for providing the maturation and proliferation process of macrophages
with sufficient energy. In addition, levels of intracellular cytokines (IL-1, TNF
alpha, NO) were significantly increased after being treated with polysaccharides.
A-PTR displayed a better performance than W-PTR in almost all tests. It is
concluded that both polysaccharides could enhance the immune system by activating
the macrophages and related enzymes, and induce the release of cytokines,
indicating that polysaccharides are responsible for the immune function of
Pleurotus tuber-regium (Fr.).
PMID- 24352759
TI - Updated guidelines for management of high blood pressure: recommendations,
review, and responsibility.
PMID- 24352760
TI - Expression of insulin-like growth factor binding protein-2 (IGFBP-2) gene in
negative and positive human cytomegalovirus glioblastoma multiforme tissues.
AB - Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most
common and lethal primary brain tumor in adults and has but few treatments. The
median survival of glioblastoma patients is 12 months. The (possible)
relationship between human cytomegalovirus (HCMV) infection and cancer has been
investigated for decades. Detection of viral DNA, mRNA and/or antigens in tumor
tissues suggests that HCMV infection has a role to play in the etiology of
several human malignancies. HCMV gene products can promote the various signaling
pathways critical to tumor growth, including platelet derived growth factor
receptor, phosphatidyl inositol 3-kinases (PI3K/AKT), signal transducer and
activator of transcription 3 and glycogen synthase kinase 3 beta that are
involved in apoptosis, angiogenesis, invasion and immune evasion. Insulin-like
growth factor binding protein 2 (IGFBP2) is a biomarker of the PI3K/AKT pathway
so we decided to evaluate the expression of this gene in 3 groups: HCMV-negative
GBM tissues, HCMV-positive GBM tissues and non-tumor tissues. The presence of
HCMV was assessed according to our previous article. HCMV was present in %75 of
glioblastoma tissues. Then RNA was extracted, cDNA was synthesized, and real-time
PCR was performed. Then, the rate of increased expression was calculated using
the Livac or 2(-DeltaDeltaCt). DeltaCt of samples in the three groups were
compared using analysis of variance (ANOVA). The expression of IGFBP2 gene
relative to GAPDH gene in HCMV-negative glioblastoma tissues and HCMV-positive
glioblastoma tissues, respectively, was increased 5.486 and 15.032 times compared
to non-neoplastic brain tissues. ANOVA tests showed that the difference of mean
DeltaCt for IGFBP2 gene between healthy subjects and patients with HCMV-positive
and HCMV-negative glioblastoma tumors statistically significant.
PMID- 24352761
TI - Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of
patients with osteosarcoma.
AB - MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in
inhibition of migration and invasion of osteosarcoma by targeting an oncogene
Ezrin. The aim of the present study was to determine the correlation of combined
miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis
in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both
examined using quantitative real-time reverse transcriptase-polymerase chain
reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and
Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma
tissues than those in noncancerous bone tissues significantly (both P < 0.001).
Notably, the downregulation of miR-183 was negatively correlated with the
upregulation of Ezrin mRNA in osteosarcoma tissues (r = -0.66, P = 0.01). In
addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183
low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02),
poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and
recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of
metastasis were both found to be independent prognostic factors for overall
survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P =
0.02). Our findings showed that the aberrant expression of miR-183 and its target
gene Ezrin may play a crucial role in the development and progression of human
osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be
related to the prediction of aggressiveness and poor prognosis for patients with
this lethal disease.
PMID- 24352762
TI - Common freshwater bacteria vary in their responses to short-term exposure to nano
TiO2.
AB - Nanostructured titania (nano-TiO2) is an engineered nanomaterial that can be
cytotoxic primarily as a result of its ability to generate reactive oxygen
species when illuminated. Production of nano-TiO2 has increased rapidly over the
last decade, leading to concerns about its release into aquatic environments. To
address the possible ecological impacts of nano-TiO2, the authors used high
throughput screening to assess the responses of 4 bacteria representative of
genera common in freshwater to short-term exposure (1-2 h) in 2 natural aqueous
media (stream water and lake water) to 2 widely used TiO2 products, pigment white
6 (PW6) and P25. Under simulated solar illumination PW6 and P25 reduced the
abundance of viable Bacillus subtilis and Aeromonas hydrophila, confirming the
cytotoxicity of nano-TiO2 . In contrast, PW6 and P25 stimulated growth of
Arthrobacter sp. and Klebsiella sp., which the authors hypothesize was driven by
oxidation of organic matter in these natural waters into more labile compounds.
This hypothesis is supported by data demonstrating PW6 photo-oxidation of organic
matter in stream water, which subsequently supported enhanced bacterial growth.
The results indicate that bacterial responses to nano-TiO2 can be species
specific, suggesting that nano-TiO2 may alter bacterial community composition and
function. Finally, the results indicate that bacterial responses to nano-TiO2 are
influenced by the water matrix, emphasizing the importance of assessing bacterial
responses to nanomaterials in natural environmental media.
PMID- 24352763
TI - Atypical growth on MRI in a case of Ewing's sarcoma despite lower SUV on PET.
AB - Ewing's sarcoma is a rare primary bone malignancy of small round blue cells.
Treatment typically consists of neoadjuvant chemotherapy, surgical resection, and
adjuvant chemotherapy. The disease response to chemotherapy can be followed with
fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures the
metabolic activity of the tumor, and by magnetic resonance imaging (MRI), which
measures tumor size. We present a unique case in which the tumor grew in size
following neoadjuvant chemotherapy but decreased in metabolic activity, making it
difficult to judge efficacy of the chemotherapy. An atypical response to
chemotherapy in this case caused tumor growth due to a fibrotic reaction while
viable tumor cells were eradicated. This case highlights the ability of FDG-PET
scan to identify the uncommon situation in which a tumor that increased in size
may have had a favorable response to chemotherapy. This possibility should be
considered in similar cases in which FDG-PET scan shows diminishing metabolic
activity despite tumor growth.
PMID- 24352765
TI - Guilt, censure, and concealment of active smoking status among cancer patients
and family members after diagnosis: a nationwide study.
AB - OBJECTIVES: We aimed to identify the prevalence of feelings of guilt, censure,
and concealment of smoking status among cancer patients and their family members
who continued to smoke after the patient's diagnosis. METHODS: Among 990 patient
family member dyads, 45 patients and 173 family members who continued to smoke
for at least 1 month after the patients' diagnoses were administered questions
examining feelings of guilt, censure, and smoking concealment. RESULTS: Most
patients who continued to smoke reported experiencing feelings of guilt toward
their families (75.6%) and censure from their family members (77.8%), and many
concealed their smoking from their family members (44.4%) or healthcare
professionals (46.7%). Family members who continued to smoke also reported
feelings of guilt with respect to the patient (63.6%) and that the patient was
critical of them (68.9%), and many concealed their smoking from the patient
(28.5%) or healthcare professionals (9.3%). Patients' feeling of guilt was
associated with concealment of smoking from family members (55.9% vs. 10.0%) or
health care professionals (55.9% vs. 20.0%). Family members who reported feeling
guilty (36.5% vs. 16.3%) or censured (34.5% vs. 16.7%) were more likely to
conceal smoking from patients. CONCLUSION: Many patients and family members
continue to smoke following cancer diagnosis, and the majority of them experience
feelings of guilt and censure, which can lead to the concealment of smoking
status from families or health care professionals. Feelings of guilt, censure,
and concealment of smoking should be considered in the development and
implementation of smoking cessation programs for cancer patients and family
members.
PMID- 24352766
TI - Efficacy of erlotinib in patients with relapsed gliobastoma multiforme who
expressed EGFRVIII and PTEN determined by immunohistochemistry.
AB - Epidermal growth factor receptor gene (EGFR) alteration is a common feature in
most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments
has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII)
and expression of PTEN. We have performed a prospective trial in order to confirm
the efficacy of erlotinib treatment in patients with relapsed GBM who expressed
EGFRvIII and PTEN. All patients included in the trial were required to be PTEN
(+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new
phase II trial enrolled 40 patients and was design to be stopped in case of fewer
than two responses in the first 13 patients. Patient eligibility included
histopathology criteria, radiological progression, more than 18 years old,
Karnofsky performed status, KPS > 50, and adequate bone marrow and organ
function. There was no limit to the number of prior treatments for relapses. No
enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were
response and progression-free survival at 6 months (PFS6). Thirteen patients (6
men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53
years, median KPS was 80, and median prior treatments for relapses were 2. There
was one partial response and three stable diseases (one at 18 months). PFS at 6
months was 20 %. Dose reduction for toxicity was not needed in any patient.
Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and
grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7
months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM
relapses patients with high protein expression for PTEN (+++), EGFR (+++), and
EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.
PMID- 24352768
TI - The impact of DSM-5's alternative model for personality disorders on criminal
defendants.
AB - The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) workgroup on
personality disorders initially proposed several revisions to diagnostic criteria
and disorder labels, some of which could have had a direct impact on the
perception and sentencing of criminal defendants. The recent publication of the
DSM-5 included these revisions in an appendix for future research, indicating
that the revised criteria require additional research before implementation. This
study examined how the proposed changes, if implemented, might affect jury
members' sentencing recommendations and perceptions of the defendant.
Participants read vignettes in which diagnostic label (antisocial personality
disorder vs. dyssocial personality disorder vs. psychopathy) and crime type
(white collar vs. violent crime) were manipulated. Results suggest that
participants perceived white collar offenders more negatively than violent
offenders, and were generally more influenced by crime type than diagnosis. The
diagnostic label was most influential on recidivism ratings and participants'
perceptions of violent offenders.
PMID- 24352769
TI - Now showing--video expansion at JBJS.
PMID- 24352770
TI - The devastating effects of tibial nonunion on health-related quality of life.
AB - BACKGROUND: Tibial nonunion is disabling, but to our knowledge no quantitative
evaluation of its effect on health-related quality of life has been reported.
METHODS: We evaluated 243 tibial shaft fracture nonunions in 237 consecutive
patients (seventy-nine female [age, 49.4 +/- 14.9 years] and 158 male [age, 46.3
+/- 15.4 years]) who were referred to a single surgeon at our tertiary care
center over a ten-year period. The most frequently affected tibial segment was
the distal third (49%), and infection was present in 18% of all cases. RESULTS:
The Short Form (SF)-12 Physical Component Summary score averaged 27.4 +/- 6.7,
indicating an extremely disabling effect on physical health. The AAOS (American
Academy or Orthopaedic Surgeons) Lower Limb Core Scale score averaged 52.0 +/-
19.4, also consistent with high levels of physical disability attributable to the
lower limb. The SF-12 Mental Component Summary score averaged 42.3 +/- 7.1,
indicating a substantial detrimental effect on mental health. CONCLUSIONS: The
impact of tibial shaft fracture nonunion on physical health was comparable with
the reported impact of end-stage hip arthrosis and worse than that of congestive
heart failure. Tibial shaft fracture nonunion is a devastating chronic medical
condition that negatively affects both physical and mental health and quality of
life.
PMID- 24352771
TI - Periprosthetic joint infection increases the risk of one-year mortality.
AB - BACKGROUND: Periprosthetic joint infection continues to potentially complicate an
otherwise successful joint replacement. The treatment of this infection often
requires multiple surgical procedures associated with increased complications and
morbidity. This study examined the relationship between periprosthetic joint
infection and mortality and aimed to determine the effect of periprosthetic joint
infection on mortality and any predictors of mortality in patients with
periprosthetic joint infection. METHODS: Four hundred and thirty-six patients
with at least one surgical intervention secondary to confirmed periprosthetic
joint infection were compared with 2342 patients undergoing revision arthroplasty
for aseptic failure. The incidence of mortality at thirty days, ninety days, one
year, two years, and five years after surgery was assessed. Multivariate analysis
was used to assess periprosthetic joint infection as an independent predictor of
mortality. In the periprosthetic joint infection population, variables
investigated as potential risk factors for mortality were evaluated. RESULTS:
Mortality was significantly greater (p < 0.001) in patients with periprosthetic
joint infection compared with those undergoing aseptic revision arthroplasty at
ninety days (3.7% versus 0.8%), one year (10.6% versus 2.0%), two years (13.6%
versus 3.9%), and five years (25.9% versus 12.9%). After controlling for age,
sex, ethnicity, number of procedures, involved joint, body mass index, and
Charlson Comorbidity Index, revision arthroplasty for periprosthetic joint
infection was associated with a fivefold increase in mortality compared with
revision arthroplasty for aseptic failures. In the periprosthetic joint infection
population, independent predictors of mortality included increasing age, higher
Charlson Comorbidity Index, history of stroke, polymicrobial infections, and
cardiac disease. CONCLUSIONS: Although it is well known that periprosthetic joint
infection is a devastating complication that severely limits joint function and
is consistently difficult to eradicate, surgeons must also be cognizant of the
systemic impact of periprosthetic joint infection and its major influence on
fatal outcome in patients.
PMID- 24352772
TI - The effect of platelet-rich plasma on autologous osteochondral transplantation:
an in vivo rabbit model.
AB - BACKGROUND: Autologous osteochondral transplantation restores a cartilage defect
with a cylindrical unit of bone and articular cartilage. Previous studies have
described poor graft integration at the chondral interface and degeneration of
the cartilage. This has prompted the investigation of adjuncts to address these
concerns, including platelet-rich plasma (PRP), which has the potential to
improve chondral interface integration and decrease cartilage degeneration. The
purpose of this study was to evaluate the effect of PRP on autologous
osteochondral transplantation in a rabbit model. METHODS: Bilateral osteochondral
defects (2.7 mm in diameter and 5 mm in depth) were created on the femoral
condyles of twelve New Zealand White rabbits. Osteochondral grafts were harvested
from the ipsilateral femoral condyle and, after randomization, were treated with
either PRP or saline solution before implantation into the defect site. The
rabbits were killed at three, six, or twelve weeks postoperatively. The
osteochondral graft was assessed using the International Cartilage Repair Society
(ICRS) macroscopic and modified ICRS histological scoring systems. RESULTS:
Macroscopic assessment revealed no significant difference between the two groups
(mean and standard deviation, 11.2 +/- 0.9 for the PRP-treated group versus 10.3
+/- 0.9 for the control group; p = 0.09). The mean modified ICRS histological
score was significantly higher overall and at each time point for the PRP-treated
osteochondral transplants compared with the controls (overall mean, 18.2 +/- 2.7
versus 13.5 +/- 3.3; p = 0.002). Assessing graft integration specifically, the
mean score for the PRP-treated group was significantly higher than that for the
control group (2.5 +/- 0.9 versus 1.6 +/- 0.7; p = 0.004). No adverse events
occurred as a result of the surgical procedure or PRP. CONCLUSIONS: PRP may
improve the integration of an osteochondral graft at the cartilage interface and
decrease graft degeneration in an in vivo animal model. CLINICAL RELEVANCE: The
use of PRP as a biological adjunct to autologous osteochondral transplantation
has the clinical potential to enhance graft integration, decrease cartilage
degeneration, and improve clinical outcomes of autologous osteochondral
transplantation.
PMID- 24352773
TI - Surgeon, implant, and patient variables may explain variability in early revision
rates reported for unicompartmental arthroplasty.
AB - BACKGROUND: The reported revision rates for cemented unicompartmental knee
arthroplasties have varied widely. The effect of implant selection, patient
characteristics, and surgeon characteristics on revision risk has not been
evaluated fully. The purpose of the present study was to determine the impact of
these variables on the risk for aseptic revision arthroplasty. METHODS: We
identified all cemented primary unicompartmental knee arthroplasties performed in
our health-care system from 2002 to 2009 (median follow-up time = 2.6 years) to
assess the risk for aseptic revision. A multivariate marginal Cox proportional
hazards model with robust standard errors (to adjust for the nesting of surgical
cases within surgeons) was used to calculate the differential risk for revision
of implants after adjusting for surgeon and hospital volume of unicompartmental
knee arthroplasties performed; surgeon experience with unicompartmental knee
arthroplasties at the time of surgery; surgeon fellowship training; and patient
age, sex, weight, body mass index, and American Society of Anesthesiologists
(ASA) score. RESULTS: A total of 1746 unicompartmental knee arthroplasties were
identified. The overall revision rate during the study period was 4.98% (95%
confidence interval [CI], 4.0% to 6.1%). In a multivariate Cox model, the hazard
ratio (HR) for aseptic revision relative to a modern, fixed, metal-backed tibial
bearing was significantly higher for an all-polyethylene tibial tray (HR = 3.85,
95% CI = 1.54 to 9.63, p = 0.004) but not significantly higher for a mobile
bearing implant (HR = 2.42, 95% CI = 0.55 to 10.65, p = 0.242) or an older
design, fixed, metal-backed bearing (HR = 1.89, 95% CI = 0.67 to 5.33, p = 0.23).
Younger age was associated with increased risk (age less than fifty-five years
compared with more than sixty-five years: HR = 4.83, 95% CI = 2.60 to 8.96, p <
0.001), and a higher ASA score (>=3 compared with <3 points: HR = 0.54, 95% CI =
0.32 to 0.93, p = 0.027) and a greater mean yearly surgeon volume of
unicompartmental knee arthroplasties (twelve or fewer compared with more than
twelve: HR = 2.18, 95% CI = 1.28 to 3.74, p = 0.004) were associated with reduced
risk. CONCLUSIONS: Implant selection can have a considerable effect on the risk
for aseptic revision following a cemented unicompartmental knee arthroplasty, as
can patient and surgeon factors. Therefore, the variation among risk estimates
reported in the literature for unicompartmental knee arthroplasty revision may be
explained by differences in patient characteristics and implant selection as well
as the surgeons' yearly volume of unicompartmental knee arthroplasties.
PMID- 24352774
TI - Failure of the glenoid component in anatomic total shoulder arthroplasty: a
systematic review of the English-language literature between 2006 and 2012.
AB - BACKGROUND: Although glenoid component failure is one of the most common
complications of anatomic total shoulder arthroplasty, substantial evidence from
the recent published literature is lacking regarding the temporal trend in the
rate of this complication and the risk factors for its occurrence. METHODS: We
conducted a systematic review and identified twenty-seven articles presenting
data on glenoid component failure rates that met the inclusion criteria. These
articles represented data from 3853 total shoulder arthroplasties performed from
1976 to 2007. RESULTS: Asymptomatic radiolucent lines occurred at a rate of 7.3%
per year after the primary shoulder replacement. Symptomatic glenoid loosening
occurred at 1.2% per year, and surgical revision occurred at 0.8% per year. There
was no significant evidence that the rate of symptomatic loosening has diminished
over time. Keeled components had greater rates of asymptomatic radiolucent lines
compared with pegged components in side-by-side comparison studies. However, as a
result of wide variability in outcomes reporting, only sex, Walch class, and
diagnosis were significantly associated with the risk of glenoid component
failure in the overall analysis. CONCLUSIONS: This is the first systematic review
of the published evidence on glenoid component failure. Although the authors of
individual articles proposed various risk factors for glenoid component failure,
many of these relationships were not significant in the present study. A
consistent methodological approach to future investigations is likely to improve
the quality of the evidence on which patients, techniques, and prostheses are
selected for total shoulder arthroplasty.
PMID- 24352775
TI - Cancer risk is not increased in patients treated for orthopaedic diseases with
autologous bone marrow cell concentrate.
AB - BACKGROUND: There is concern that regenerative cell-based therapies could result
in increased risk of tumor formation. We investigated the long-term risks for
systemic and site-specific cancers in patients who had received autologous bone
marrow-derived stromal progenitor cells to treat orthopaedic lesions. METHODS: A
total of 1873 patients were treated from 1990 to 2006 with bone marrow-derived
concentrated cells. Patients were monitored for cancer incidence from the date of
the first operation (1990) until death, or until December 31, 2011. The mean
follow-up time was 12.5 years (range, five to twenty-two years). The average
number of colony-forming unit fibroblasts returned to the patients was 483,000
fibroblasts (range, 62,000 to 2,095,000 fibroblasts). The primary outcome was to
evaluate with radiographs and/or magnetic resonance imaging the risk of
tumorigenesis at the cell therapy treatment sites. The secondary outcome was to
evaluate the risk of cancer diagnosed in areas other than the treatment site
during the follow-up period. The relative risk of cancer was expressed as the
ratio of observed and expected number of cases, that is, the standardized
incidence ratio, according to the cancer incidence in the French population.
RESULTS: No tumor formation was found at the treatment sites on the 7306 magnetic
resonance images and 52,430 radiographs among the 1873 patients. Fifty-three
cancers were diagnosed in areas other than the treatment site. On the basis of
cancer incidence in the general population during the same period, the expected
number of cancers was between ninety-seven and 108 for the same age and sex
distribution. The range of the standardized incidence ratio for the follow-up
period was between 0.49 and 0.54 (95% confidence interval, 0.30 to 0.80).
CONCLUSIONS: This study found no increased cancer risk in patients after
application of autologous cell-based therapy using bone marrow-derived stromal
progenitor cells either at the treatment site or elsewhere in the patients after
an average follow-up period of 12.5 years.
PMID- 24352776
TI - What's new in primary malignant musculoskeletal tumors.
PMID- 24352777
TI - Ankle arthroplasty and ankle arthrodesis: gait analysis compared with normal
controls.
AB - BACKGROUND: This study compared patients with isolated end-stage ankle
osteoarthritis, after undergoing either total ankle arthroplasty or arthrodesis,
using gait analysis and patient-reported outcome measures to elucidate
differences between the two treatment options, as compared with a healthy control
group. METHODS: Gait analyses were performed on patients with isolated ankle
arthritis more than one year after undergoing either total ankle arthroplasty or
arthrodesis during a ten-year period. Validated outcome questionnaire data were
obtained. Seventeen patients undergoing total ankle arthroplasty, seventeen
patients undergoing arthrodesis, and ten matched control subjects were included
for comparison. RESULTS: Patients who had undergone arthroplasty, when compared
with patients who had undergone arthrodesis, demonstrated greater postoperative
total sagittal plane motion (18.1 degrees versus 13.7 degrees ; p < 0.05),
dorsiflexion (11.9 degrees versus 6.8 degrees ; p < 0.05), and range of tibial
tilt (23.1 degrees versus 19.1 degrees ; p < 0.05). Plantar flexion motion was
not equivalent to normal in either group. Ankle moments and power in both
treatment groups remained significantly lower compared with the control group (p
< 0.05 between each treatment group and the control group for both variables).
Gait patterns in both treatment groups were not completely normalized.
Improvements in patient-reported Ankle Osteoarthritis Scale and Short Form-36
scores were similar for both treatment groups. CONCLUSIONS: The gait patterns of
patients following three-component, mobile-bearing total ankle arthroplasty more
closely resembled normal gait when compared with the gait patterns of patients
following arthrodesis. Dorsal motion in the sagittal plane was primarily
responsible for the differences. Improvement in self-reported clinical outcome
scores was similar for both groups. Further investigation is needed to determine
why patients who have undergone total ankle arthroplasty do not use the plantar
flexion motion in the terminal-stance phase and to explain the limited increase
in power generation at toe-off after arthroplasty. Results obtained from this
study may be used for future modifications of ankle prostheses and may add to
clinicians' ability to inform patients of predicted functional outcomes prior to
the treatment of end-stage ankle osteoarthritis.
PMID- 24352778
TI - Effect and possible mechanism of muscle-splitting approach on multifidus muscle
injury and atrophy after posterior lumbar spine surgery.
AB - BACKGROUND: Multifidus muscle injury and atrophy are common after posterior
lumbar spine surgery and are associated with low back pain and functional
disability. In theory, muscle-splitting and retraction with a self-retaining
retractor are considered to be the major surgical factors. The effects and
mechanisms of retraction have been well studied, but the exact effect and
possible mechanism of injury and atrophy after muscle-splitting still lack
experimental evidence. METHODS: New Zealand White rabbits were divided into two
groups. In group S, through a skin and lumbodorsal fascial incision, the
bilateral multifidus muscles were dissected from the osseous structures in the
standard fashion, while in group C, only a skin and lumbodorsal fascial incision
was made. In each group, the multifidus muscle was evaluated by magnetic
resonance imaging (MRI) and by histological analysis at three and forty-eight
hours and at one, three, six, twelve, and twenty-four weeks after surgery.
RESULTS: In group C, there was no injury or atrophy of the multifidus muscle
after surgery. In group S, the mean T2-weighted signal intensity ratios of gross
multifidus to psoas on fat-suppressed T2-weighted cross-sectional MRI scans
peaked on week 3 and returned to baseline on week 24. Necrosis and inflammation
of the multifidus muscle were evident and became more severe at one week.
Fibrotic change was mainly seen at three and six weeks after surgery, and fatty
degeneration mainly occurred at twelve and twenty-four weeks. Decreased
acetylcholine activity and granular degeneration of the neuromuscular junction
were observed at all follow-up times, and the numbers of degenerating
neuromuscular junctions increased significantly with time after surgery.
CONCLUSIONS: The splitting approach is an important cause of multifidus muscle
injury and atrophy in posterior lumbar spine surgery. Denervation and disuse may
be important factors in multifidus muscle atrophy in the splitting approach.
CLINICAL RELEVANCE: This study provides a basis for the prevention of multifidus
muscle injury and atrophy after posterior lumbar surgery.
PMID- 24352779
TI - Spontaneous improvement of radiographic indices for idiopathic planovalgus with
age.
AB - BACKGROUND: The prevalence of idiopathic planovalgus decreases with age among
children and adolescents. Previous studies have provided averages of radiographic
indices for different age groups but not information about the rate of
spontaneous correction and the affecting factors. The aim of this study was to
estimate the rate of spontaneous improvement of radiographic indices of
idiopathic planovalgus through the application of a linear mixed model. METHODS:
We included patients with idiopathic planovalgus who were no older than the age
of fifteen years, who had had two or more weight-bearing foot radiographs made,
and who were followed for more than one year. The talonavicular coverage angle,
the anteroposterior talus-first metatarsal angle, the calcaneal pitch angle, and
the lateral talus-first metatarsal angle were measured on the radiographs. The
rate of angular correction was adjusted by multiple factors with the use of a
linear mixed model, with sex and laterality as the fixed effects and age and each
subject as the random effects. RESULTS: A total of 568 feet were included in this
study, and a total of 3284 radiographs were measured. The talonavicular coverage
angle was found to have decreased by 1.7 degrees per year (p < 0.001); the
anteroposterior talus-first metatarsal angle, by 2.1 degrees per year (p <
0.001); and the lateral talus-first metatarsal angle, by 0.7 degrees per year (p
= 0.034). The spontaneous improvement of the calcaneal pitch with aging was not
significant. CONCLUSIONS: The talonavicular coverage angle and the
anteroposterior talus-first metatarsal angle on anteroposterior radiographs and
the lateral talus-first metatarsal angle on lateral radiographs improved as
patients with idiopathic planovalgus grew older. These findings can assist in the
prediction of the radiographic improvement of idiopathic planovalgus.
PMID- 24352780
TI - Traumatic atlanto-occipital dislocation in children: evaluation, treatment, and
outcomes.
AB - BACKGROUND: Advancements in emergency care and diagnostic methods have increased
the number of children who survive atlanto-occipital dislocation. We report our
experience with one of the largest series of pediatric patients with atlanto
occipital dislocation. METHODS: Patients ranging in age from newborn to sixteen
years old who had a diagnosis of atlanto-occipital dislocation from 1991 through
2011 were identified. Inclusion criteria were complete radiographic and clinical
records and duration of follow-up of at least six months. Basic patient
characteristics, mechanism of injury, associated injuries, neurological
impairment, surgical treatment and type of implant used for fixation,
complications, and clinical and radiographic outcomes were recorded. RESULTS: The
fourteen patients who were included (seven male and seven female) had a mean age
of 5.2 years at the time of injury. An automobile accident in which the victim
was a passenger was the most common mechanism of injury. Twelve patients had
associated injuries, with a brain injury in eleven of them, and nearly half
sustained a spinal cord injury. According to the Traynelis classification system,
eight patients had a type-II (longitudinal) atlanto-occipital dislocation, five
had a type-I (anterior) dislocation, and one had a type-III (posterior)
dislocation. All patients had posterior occipitocervical fusion with internal
fixation. The mean duration of follow-up was 75.4 months. The most common
postoperative complication was hydrocephalus, which occurred in four patients.
Spinal fusion occurred in all patients by four to six months postoperatively. At
the time of the most recent follow-up evaluation, half of the patients had
neurological impairment. CONCLUSIONS: More patients with atlanto-occipital
dislocation now survive the initial trauma, although most have associated
injuries and many have neurological impairment. Our preferred management is early
occipitocervical fusion and stabilization. If there is neurological decline after
spinal fixation, obstructive hydrocephalus should be suspected.
PMID- 24352781
TI - Neurovascular entrapment due to combat-related heterotopic ossification in the
lower extremity.
AB - BACKGROUND: Heterotopic ossification is the ectopic formation of mature lamellar
bone in nonosseous tissue. The prevalence of heterotopic ossification following
combat injuries is much higher than civilian data would suggest. In certain
cases, the aberrant bone formation can envelop major neurovascular structures in
the lower extremity, leading to symptomatic neurovascular entrapment. METHODS: We
describe five consecutive cases of heterotopic ossification leading to
symptomatic neurovascular entrapment in the lower extremity as a result of blast
trauma and present our method of patient assessment, preoperative planning, and
surgical excision. RESULTS: Heterotopic bone was successfully excised without
neurovascular injury in all patients. At a mean of twenty months (range, eight to
forty-five months) postoperatively, all patients demonstrated continued
improvement of their pre-excision function. All patients who had neuropathic pain
had a decrease in the pain. Those with decreased joint motion regained motion
once their wounds were stable. Sensory deficits resolved before motor deficits
did. There was no recurrence of clinically relevant heterotopic ossification in
this series. CONCLUSIONS: Excision of heterotopic bone, particularly with
concurrent neurovascular entrapment, can be associated with major short-term and
long-term complications. With use of our treatment algorithm, involving careful
preoperative planning and meticulous operative excision, heterotopic bone
entrapping major neurovascular structures following severe extremity trauma can
be safely excised with subsequent clinical improvement.
PMID- 24352782
TI - Upper-extremity peripheral nerve blocks in the perioperative pain management of
orthopaedic patients: AAOS exhibit selection.
AB - BACKGROUND: Over the past twenty-five years, peripheral nerve blocks have become
increasingly common for the management of perioperative pain of the upper
extremity. Several factors have led to increasing acceptance and use of these
peripheral nerve blocks, including a greater awareness and measurement of patient
pain and a greater emphasis on decreasing the duration of hospital stays and
associated costs. METHODS: We present a review of peripheral nerve blocks for
procedures involving the upper extremity, including indications,
contraindications, anatomy and technique, expected clinical outcomes and the
associated levels of evidence, cost-effectiveness, and complications. We reviewed
the scientific literature for studies on the effectiveness of peripheral nerve
blocks for orthopaedic procedures involving the upper extremity. Particular
attention was directed at the most commonly used nerve blocks, the levels of
evidence supporting their use, and emerging technologies such as ultrasonographic
guidance. RESULTS: Peripheral nerve blocks for upper-extremity procedures improve
postoperative pain control and patient satisfaction, can be administered safely,
and have a low complication rate. They are also associated with enhanced
participation in postoperative rehabilitation, decreased hospital stays, and
decreased costs. There are increasingly higher levels of evidence in the
literature to support the use of peripheral nerve blocks in a wide variety of
orthopaedic procedures ranging from the shoulder to the hand. CONCLUSIONS: The
use of peripheral nerve blocks in upper-extremity surgery is common. To actively
participate with the patient and anesthesiologist to ensure the best possible
outcomes, the orthopaedic surgeon must be well informed regarding the benefits
and limitations of this modality.
PMID- 24352783
TI - Ankle fracture eponyms.
PMID- 24352784
TI - Tibial nonunion is worse than having a myocardial infarction: Commentary on an
article by Mark R. Brinker, MD, et al.: "The devastating effects of tibial
nonunion on health-related quality of life".
PMID- 24352785
TI - Does the infection or the treatment kill the patient?: Commentary on an article
by Benjamin Zmistowski, BS, et al.: "Periprosthetic joint infection increases the
risk of one-year mortality".
PMID- 24352787
TI - High-fidelity protein targeting into membrane lipid microdomains in living cells.
AB - Lipid analogues carrying three nitrilotriacetic acid (tris-NTA) head groups were
developed for the selective targeting of His-tagged proteins into liquid ordered
(lo ) or liquid disordered (ld ) lipid phases. Strong partitioning into the lo
phase of His-tagged proteins bound to tris-NTA conjugated to saturated alkyl
chains (tris-NTA DODA) was achieved, while tris-NTA conjugated to an unsaturated
alkyl chain (tris-NTA SOA) predominantly resided in the ld phase. Interestingly,
His-tag-mediated lipid crosslinking turned out to be required for efficient
targeting into the lo phase by tris-NTA DODA. Robust partitioning into lo phases
was confirmed by using viral lipid mixtures and giant plasma membrane vesicles.
Moreover, efficient protein targeting into lo and ld domains within the plasma
membrane of living cells was demonstrated by single-molecule tracking, thus
establishing a highly generic approach for exploring lipid microdomains in situ.
PMID- 24352789
TI - Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand
for the diagnosis of recurrent prostate cancer: initial experience.
AB - PURPOSE: (68)Ga-labelled HBED-CC-PSMA is a highly promising tracer for imaging
recurrent prostate cancer (PCa). The intention of this study was to evaluate the
feasibility of PET/MRI with this tracer. METHODS: Twenty patients underwent
PET/CT 1 h after injection of the (68)Ga-PSMA ligand followed by PET/MRI 3 h
after injection. Data from the two investigations were first analysed separately
and then compared with respect to tumour detection rate and radiotracer uptake in
various tissues. To evaluate the quantification accuracy of the PET/MRI system,
differences in SUVs between PET/CT and corresponding PET/MRI were compared with
differences in SUVs between PET/CT 1 h and 3 h after injection in another patient
cohort. This cohort was investigated using the same PET/CT system. RESULTS: With
PET/MRI, different diagnostic sequences, higher contrast of lesions and higher
resolution of MRI enabled a subjectively easier evaluation of the images. In
addition, four unclear findings on PET/CT could be clarified as characteristic of
PCa metastases by PET/MRI. However, in PET images of the PET/MRI, a reduced
signal was observed at the level of the kidneys (in 11 patients) and around the
urinary bladder (in 15 patients). This led to reduced SUVs in six lesions.
SUVmean values provided by the PET/MRI system were different in muscles, blood
pool, liver and spleen. CONCLUSION: PCa was detected more easily and more
accurately with Ga-PSMA PET/MRI than with PET/CT and with lower radiation
exposure. Consequently, this new technique could clarify unclear findings on
PET/CT. However, scatter correction was challenging when the specific (68)Ga-PSMA
ligand was used. Moreover, direct comparison of SUVs from PET/CT and PET/MR needs
to be conducted carefully.
PMID- 24352790
TI - Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic
deficits of Rett syndrome.
AB - Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM
312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes
MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2
mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1
mutations but not exon 2 mutations have been identified in RTT patients,
suggesting that MeCP2-e1 deficiency is sufficient to cause RTT. As expected,
genetic deletion of Mecp2 exons 3 and/or 4 recapitulates RTT-like neurologic
defects in mice. However, Mecp2 exon 2 knockout mice have normal neurologic
function. Here, a naturally occurring MECP2 exon 1 mutation is recapitulated in a
mouse model by genetic engineering. A point mutation in the translational start
codon of Mecp2 exon 1, transmitted through the germline, ablates MeCP2-e1
translation while preserving MeCP2-e2 production in mouse brain. The resulting
MeCP2-e1 deficient mice developed forelimb stereotypy, hindlimb clasping,
excessive grooming and hypo-activity prior to death between 7 and 31 weeks. MeCP2
e1 deficient mice also exhibited abnormal anxiety, sociability and ambulation.
Despite MeCP2-e1 and MeCP2-e2 sharing, 96% amino acid identity, differences were
identified. A fraction of phosphorylated MeCP2-e1 differed from the bulk of MeCP2
in subnuclear localization and co-factor interaction. Furthermore, MeCP2-e1
exhibited enhanced stability compared with MeCP2-e2 in neurons. Therefore, MeCP2
e1 deficient mice implicate MeCP2-e1 as the sole contributor to RTT with non
redundant functions.
PMID- 24352791
TI - Effects of training condition on the contribution of specific items to relational
processing in baboons (Papio papio).
AB - Relational processing involves learning about the relationship between or among
stimuli, transcending the individual stimuli, so that abstract knowledge
generalizable to novel situations is acquired. Relational processing has been
studied in animals as well as in humans, but little attention has been paid to
the contribution of specific items to relational thinking or to the factors that
may affect that contribution. This study assessed the intertwined effects of item
and relational processing in nonhuman primates. Using a procedure that entailed
both expanding and contracting sets of pictorial items, we trained 13 baboons on
a two-alternative forced-choice task, in which they had to distinguish horizontal
from vertical relational patterns. In Experiment 1, monkeys engaged in item-based
processing with a small training set size, and they progressively engaged in
relation-based processing as training set size was increased. However, in
Experiment 2, overtraining with a small stimulus set promoted the processing of
item-based information. These findings underscore similarities in how humans and
nonhuman primates process higher-order stimulus relations.
PMID- 24352792
TI - A pain in the arms.
PMID- 24352793
TI - The previous use of digoxin does not worsen early outcome of acute coronary
syndromes: an analysis of the ARIAM Registry.
AB - The aim of the study was to determine the influence of the previous use of
digoxin on the hospital mortality and complications of patients admitted because
of acute coronary syndrome (ACS). We analyzed the data of patients included in
the ARIAM-Andalucia Registry, which involves 49 hospitals in Andalucia, Spain,
from 2007 to 2012. Patients on digoxin treatment prior to their admission because
of ACS constituted the digoxin group (DG), and were compared with the group of
patients not on digoxin. Logistic regression and propensity score matching were
used to analyze the differences. We included 20,331 patients, of whom 244 (1.2%)
were on digoxin. DG patients were older (73.1 vs 63.7 years old), more often
women, and had more diabetes, hypertension, previous myocardial infarction, heart
failure, stroke, atrial fibrillation, peripheral vascular disease, obstructive
pulmonary disease or kidney disease. On univariate analysis, DG patients had
significantly higher hospital mortality (13.5 vs 5.3% P < 0.001), and more
cardiogenic shock, but less ventricular fibrillation, and no differences in
atrioventricular block, stroke or reinfarction. After the multivariate analysis,
DG had no significant influence on hospital prognosis [odds ratio (OR) 1.21, 95%
confidence interval 0.79-1.86]. The analysis of a propensity-matched cohort of
464 patients (232 DG and 232 NoDG) did not find differences in hospital mortality
(13.4 vs 13.4%) nor other complications. In our cohort of ACS patients, the
previous treatment with digoxin was not associated with an increase in
dysrhythmic complications nor was an independent predictor of mortality during
hospitalization.
PMID- 24352794
TI - Hypokalemia-induced rhabdomyolysis.
PMID- 24352795
TI - Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in
relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic
lymphocytic leukemia.
AB - PURPOSE: Amplification or over-expression of the mitotic Aurora A kinase (AAK)
has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is
a novel inhibitor of AAK that is being developed for the treatment of advanced
malignancies. The objectives of this phase I study were to establish the safety,
tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in
patients with relapsed or refractory heme-lymphatic malignancies. METHODS:
Sequential cohorts of patients received MLN8237 orally as either a powder-in
capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received
MLN8237 PIC 25-90 mg for 14 or 21 consecutive days plus 14 or 7 days' rest,
respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for
14 days plus 14 days' rest, all in 28-day cycles. Subsequent cohorts received
MLN8237 ECT 30-50 mg twice-daily (BID) for 7 days plus 14 days' rest in 21-day
cycles. RESULTS: Fifty-eight patients were enrolled (PIC n = 28, ECT n = 30). The
most frequent grade >=3 drug-related toxicities were neutropenia (45 %),
thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum
tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of
MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses
and 13 (28 %) stable disease. CONCLUSION: The recommended phase II dose of
MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being
evaluated as a single agent in phase II/III trials in patients with peripheral T
cell lymphoma.
PMID- 24352796
TI - The functional consequences of intron retention: alternative splicing coupled to
NMD as a regulator of gene expression.
AB - The explosion in sequencing technologies has provided us with an instrument to
describe mammalian transcriptomes at unprecedented depths. This has revealed that
alternative splicing is used extensively not only to generate protein diversity,
but also as a means to regulate gene expression post-transcriptionally. Intron
retention (IR) is overwhelmingly perceived as an aberrant splicing event with
little or no functional consequence. However, recent work has now shown that IR
is used to regulate a specific differentiation event within the haematopoietic
system by coupling it to nonsense-mediated mRNA decay (NMD). Here, we highlight
how IR and, more broadly, alternative splicing coupled to NMD (AS-NMD) can be
used to regulate gene expression and how this is deregulated in disease. We
suggest that the importance of AS-NMD is not restricted to the haematopoietic
system but that it plays a prominent role in other normal and aberrant biological
settings.
PMID- 24352797
TI - 2014 evidence-based guideline for the management of high blood pressure in
adults: report from the panel members appointed to the Eighth Joint National
Committee (JNC 8).
AB - Hypertension is the most common condition seen in primary care and leads to
myocardial infarction, stroke, renal failure, and death if not detected early and
treated appropriately. Patients want to be assured that blood pressure (BP)
treatment will reduce their disease burden, while clinicians want guidance on
hypertension management using the best scientific evidence. This report takes a
rigorous, evidence-based approach to recommend treatment thresholds, goals, and
medications in the management of hypertension in adults. Evidence was drawn from
randomized controlled trials, which represent the gold standard for determining
efficacy and effectiveness. Evidence quality and recommendations were graded
based on their effect on important outcomes. There is strong evidence to support
treating hypertensive persons aged 60 years or older to a BP goal of less than
150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic
goal of less than 90 mm Hg; however, there is insufficient evidence in
hypertensive persons younger than 60 years for a systolic goal, or in those
younger than 30 years for a diastolic goal, so the panel recommends a BP of less
than 140/90 mm Hg for those groups based on expert opinion. The same thresholds
and goals are recommended for hypertensive adults with diabetes or nondiabetic
chronic kidney disease (CKD) as for the general hypertensive population younger
than 60 years. There is moderate evidence to support initiating drug treatment
with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker,
calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive
population, including those with diabetes. In the black hypertensive population,
including those with diabetes, a calcium channel blocker or thiazide-type
diuretic is recommended as initial therapy. There is moderate evidence to support
initial or add-on antihypertensive therapy with an angiotensin-converting enzyme
inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney
outcomes. Although this guideline provides evidence-based recommendations for the
management of high BP and should meet the clinical needs of most patients, these
recommendations are not a substitute for clinical judgment, and decisions about
care must carefully consider and incorporate the clinical characteristics and
circumstances of each individual patient.
PMID- 24352798
TI - Facilitators and barriers to help-seeking for breast and cervical cancer
symptoms: a qualitative study with an ethnically diverse sample in London.
AB - OBJECTIVE: Earlier diagnosis of cancer has become a policy priority. There is
evidence that minority ethnic groups are more likely to delay help-seeking for
cancer symptoms, but few studies have explored reasons for delay in these groups.
The present study explored facilitators and barriers to help-seeking for breast
and cervical cancer in an ethnically diverse sample of women. METHODS: Semi
structured interviews were carried out with 54 healthy women from a range of
ethnic backgrounds; Indian, Pakistani, Bangladeshi, Caribbean, African, Black
British, Black other, White British and White other. Framework analysis was used
to identify themes. RESULTS: Appraising a symptom as possibly due to cancer was
an important facilitator of help-seeking, although for some the prospect of a
cancer diagnosis was a deterrent. Women believed that earlier diagnosis improved
the chance of survival, and this facilitated prompt help-seeking. A sympathetic
GP facilitated help-seeking, and an unsympathetic GP was a deterrent. Some ethnic
minority women described the use of alternative medicine and prayer as a first
line strategy that might delay help-seeking. Language barriers, racism and a
tendency to 'soldier on' were also mentioned by these women. CONCLUSIONS: Models
of delay in presentation for early cancer symptoms are likely to transfer across
different ethnic groups. Encouraging open discussion about cancer among minority
communities could help raise awareness about the importance of early detection
and promote help-seeking as a priority response to a possible cancer symptom.
PMID- 24352799
TI - Theoretical and experimental determination of the absorption and emission spectra
of a prototypical indolenine-based squaraine dye.
AB - The spectroscopy of a prototypical indolenine-based squaraine dye is analysed
theoretically using state-of-the-art methodologies for the simulation of spectral
lineshapes, and experimentally using optical absorption and emission
spectroscopies. Density functional theory and its time-dependent extension are
used to determine the stability of several conformers, to compute their
excitation energies, equilibrium geometries and vibrational frequencies, both in
the ground and in their first excited singlet state. Finally the generating
function approach is used to simulate the vibronic lineshape of the low energy
valence pipi* excitation and emission spectra. Solvent effects are also computed
and discussed by using the polarizable continuum model. The developed model
correctly reproduces the main spectral features of the squaraine, and allows us
to identify the vibrational motions that mainly contribute to the observed
lineshape.
PMID- 24352800
TI - Self-organization and nanostructural control in thin film heterojunctions.
AB - In spite of more than two-decades of studies of molecular self-assembly, the
achievement of low cost, easy-to-implement and multi-parameter bottom-up
approaches to address the supramolecular morphology in three-dimensional (3D)
systems is still missing. In the particular case of molecular thin films, the 3D
nanoscale morphology and function are crucial for both fundamental and applied
research. Here we show how it is possible to tune the 3D film structure (domain
size, branching, etc.) of thin film heterojunctions with nanoscale accuracy
together with the modulation of their optoelectronic properties by employing an
easy two-step approach. At first we prepared multi-planar heterojunctions with a
programmed sequence of nanoscopic layers. In a second step, thermal stimuli have
been employed to induce the formation of bulk heterojunctions with bicontinuous
and interdigitated phases having a size below the exciton diffusion length.
Importantly, the study of luminescence quenching of these systems can be
considered as a useful means for the accurate estimation of the exciton diffusion
length of semiconductors in nanoscale blends. Finally, nearly a thousand times
lower material consumption than spin coating allows a drastic reduction of
material wasting and a low-cost implementation, besides the considerable
possibility of preparing thin film blends also by employing materials soluble in
different solvents.
PMID- 24352801
TI - 15-Deoxy-?12,14-PGJ 2, by activating peroxisome proliferator-activated receptor
gamma, suppresses p22phox transcription to protect brain endothelial cells
against hypoxia-induced apoptosis.
AB - 15-Deoxy-?(12,14)-PGJ(2) (15d-PGJ(2)) and thiazolidinedione attenuate reactive
oxygen species (ROS) production via a peroxisome proliferator-activated receptor
gamma (PPAR-gamma)-dependent pathway. Nonetheless, how PPAR-gamma mediates ROS
production to ameliorate ischemic brain injury is not clear. Recent studies
indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the
major source of ROS in the vascular system. In the present study, we used an in
vitro oxygen-glucose deprivation and reoxygenation (hypoxia reoxygenation [HR])
paradigm to study whether PPAR-gamma interacts with NADPH oxidase, thereby
regulating ROS formation in cerebral endothelial cells (CECs). With
pharmacological (PPAR-gamma antagonist GW9662), loss-of-function (PPAR-gamma
siRNA), and gain-of-function (Ad-PPAR-gamma) approaches, we first demonstrated
that 15d-PGJ(2) protected HR-treated CECs against ROS-induced apoptosis in a PPAR
gamma-dependent manner. Results of promoter and subcellular localization analyses
further revealed that 15d-PGJ(2), by activating PPAR-gamma, blocked HR-induced NF
kappaB nuclear translocation, which led to inhibited transcription of the NADPH
oxidase subunit p22phox. In summary, we report a novel transrepression mechanism
whereby PPAR-gamma downregulates hypoxia-activated p22phox transcription and the
subsequent NADPH oxidase activation, ROS formation, and CEC apoptosis.
PMID- 24352802
TI - The roles of p38 MAPK/MSK1 signaling pathway in the neuroprotection of hypoxic
postconditioning against transient global cerebral ischemia in adult rats.
AB - Postconditioning has regenerated interest as a mechanical intervention against
cerebral ischemia/reperfusion injury, but its molecular mechanisms remain
unknown. We previously reported that hypoxic postconditioning (HPC) ameliorated
neuronal death induced by transient global cerebral ischemia (tGCI) in
hippocampal CA1 subregion of adult rats. This study tested the hypothesis that
p38-mitogen-activated protein kinase (p38 MAPK)/mitogen- and stress-response
kinase 1 (MSK1) signaling pathway plays a role in the HPC-induced
neuroprotection. Male Wistar rats were subjected to 10 min ischemia induced by
applying the four-vessel occlusion method. HPC with 120 min was applied at 24 h
after reperfusion. Immunohistochemistry and Western blot were used to detect the
expression of phosphorylation of p38 MAPK and MSK1, as well as cleaved caspase-3.
We found that HPC induced a significant increase of phosphorylated p38 MAPK and
MSK1 in neurons of hippocampal CA1 region and a significant decrease in glial
cells after tGCI as well. Furthermore, HPC attenuated caspase-3 cleavation
triggered by tGCI in CA1 region. Moreover, p38 MAPK inhibition by SB203580
significantly decreased the phosphorylation of MSK1, increased cleaved caspase-3
expression, and abolished the neuroprotection of HPC. These findings suggested
that p38 MAPK/MSK1 signaling axis contributed to HPC-mediated neuroprotection
against tGCI, at least in part, by regulating the activation of caspase-3.
PMID- 24352804
TI - PAC1-expressing structures of neural retina alter their PAC1 isoform splicing
during postnatal development.
AB - Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the
secretin/glucagon/vasoactive intestinal peptide family, exerts various effects on
neuronal development as mediated by the differential expression of PAC1 receptor
(PAC1-R) isoforms. The expression changes of PAC1-R isoforms (Hip, Hop1) reported
in correlation with retinal development suggest an isoform switch during the
second postnatal week. Our aim is to determine the exact period of the isoform
shift and to describe the PAC1-R-immunoreactive structures appearing from
postnatal day 5 (P5) to P10 in the rat retina. The ratio of Hip and Hop1
receptors was assessed and changes in their expression were followed by Taqman
and SybrGreen-based quantitative polymerase chain reaction. For the detection of
PAC1-R-expressing retinal structures, anti-PAC1-R, anti-calbindin, anti-protein
kinase C, anti-glutamine synthetase, anti-HPC1 and anti-Brn3a antibodies were
utilized. At the transcript level, a marked decrease to an undetectable level was
measured in Hip mRNA expression from P6 to P9. Hop1 expression appeared to be
unchanged from P6 to P9, followed by a significant elevation at P10. A Hip/Hop1
isoform shift occurred between P6 and P7. Immunostaining showed strong PAC1-R
labeling from P5 to P10 in ganglion, amacrine, horizontal and rod bipolar neurons
and in glial Muller cell processes. The Hop1 isoform was predominantly expressed
in various types of retinal cell beginning at P7, because of a dramatic reduction
in Hip mRNA level. As the Hop1 receptor is coupled to different signaling
cascades, this isoform shift might alter the physiological role of PACAP during
this particular period.
PMID- 24352805
TI - Glucocorticoids and endothelial cell barrier function.
AB - Glucocorticoids (GCs) are steroid hormones that have inflammatory and
immunosuppressive effects on a wide variety of cells. They are used as therapy
for inflammatory disease and as a common agent against edema. The blood brain
barrier (BBB), comprising microvascular endothelial cells, serves as a
permeability screen between the blood and the brain. As such, it maintains
homeostasis of the central nervous system (CNS). In many CNS disorders, BBB
integrity is compromised. GC treatment has been demonstrated to improve the
tightness of the BBB. The responses and effects of GCs are mediated by the
ubiquitous GC receptor (GR). Ligand-bound GR recognizes and binds to the GC
response element located within the promoter region of target genes.
Transactivation of certain target genes leads to improved barrier properties of
endothelial cells. In this review, we deal with the role of GCs in endothelial
cell barrier function. First, we describe the mechanisms of GC action at the
molecular level. Next, we discuss the regulation of the BBB by GCs, with emphasis
on genes targeted by GCs such as occludin, claudins and VE-cadherin. Finally, we
present currently available GC therapeutic strategies and their limitations.
PMID- 24352807
TI - Is brief advice in primary care a cost-effective way to promote physical
activity?
AB - AIM: This study models the cost-effectiveness of brief advice (BA) in primary
care for physical activity (PA) addressing the limitations in the current limited
economic literature through the use of a time-based modelling approach. METHODS:
A Markov model was used to compare the lifetime costs and outcomes of a cohort of
100 000 people exposed to BA versus usual care. Health outcomes were expressed in
terms of quality-adjusted life years (QALYs). Costs were assessed from a health
provider perspective (L2010/11 prices). Data to populate the model were derived
from systematic literature reviews and the literature searches of economic
evaluations that were conducted for national guidelines. Deterministic and
probability sensitivity analyses explored the uncertainty in parameter estimates
including short-term mental health gains associated with PA. RESULTS: Compared
with usual care, BA is more expensive, incurring additional costs of L806 809 but
it is more effective leading to 466 QALYs gained in the total cohort, a QALY gain
of 0.0047/person. The incremental cost per QALY of BA is L1730 (including mental
health gains) and thus can be considered cost-effective at a threshold of L20
000/QALY. Most changes in assumptions resulted in the incremental cost
effectiveness ratio (ICER) falling at or below L12 000/QALY gained. However, when
short-term mental health gains were excluded the ICER was L27 000/QALY gained.
The probabilistic sensitivity analysis showed that, at a threshold of L20
000/QALY, there was a 99.9% chance that BA would be cost-effective. CONCLUSIONS:
BA is a cost-effective way to improve PA among adults, provided short-term mental
health gains are considered. Further research is required to provide more
accurate evidence on factors contributing to the cost-effectiveness of BA.
PMID- 24352806
TI - Homologous and heterologous desensitization of guanylyl cyclase-B signaling in
GH3 somatolactotropes.
AB - The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C
type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary,
CNP and GC-B are major regulators of cGMP production in gonadotropes and yet
mouse models of disrupted CNP and GC-B indicate a potential role in growth
hormone secretion. In the current study, we investigate the molecular and
pharmacological properties of the CNP/GC-B system in somatotrope lineage cells.
Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC
B receptors that had similar EC50 properties in terms of cGMP production.
Interestingly, GC-B signaling underwent rapid homologous desensitization in a
protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or
ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP
accumulation in a ligand-specific manner. However, this down-regulation was not
accompanied by alterations in the sub-cellular localization of these receptors.
Heterologous desensitization of GC-B signaling occurred in GH3 cells following
exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone
(TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as
pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling.
Collectively, these data indicate common and distinct properties of particulate
guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms
of homologous and heterologous desensitization occur involving either PP2A or
PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic
targets for treating growth-hormone-associated disorders.
PMID- 24352808
TI - Emergency contraception, institutional conscience, and pharmacy practice.
AB - "Emergency contraception" case law from the state of Washington is reviewed and
analyzed. Important legal, social policy, and professional ethical questions are
considered with focus on professional and institutional conscientious objection
to participating in this therapy.
PMID- 24352809
TI - Promoting pharmacy-based referrals to the tobacco quitline: a pilot study of
academic detailing administered by pharmacy students.
AB - OBJECTIVE: To conduct a pilot study of a student-delivered academic detailing
initiative to promote brief, pharmacy-based tobacco cessation interventions, and
referrals to the tobacco quitline. METHODS: Pharmacy students (n = 11) received
training and delivered academic detailing sessions for promoting brief tobacco
cessation interventions at community pharmacies (n = 37). Six months after the
session, a survey was faxed to each pharmacy to assess (1) the quality and
acceptance of the academic detailing session and the materials provided during
the session and (2) tobacco cessation counseling perceptions and practices.
RESULTS: Pharmacists from 30 (81%) sites responded to the survey; of these, 37%
reported that they increased the number of patients asked about smoking since the
academic detailing session, 70% reported an increase in the number of
participants advised to quit smoking, 57% reported an increase in the number of
patients counseled, and 50% reported routinely providing referrals to the tobacco
quitline. CONCLUSION: pharmacy students are capable of providing academic
detailing for brief tobacco cessation interventions in community pharmacies.
Results of this pilot study suggest a positive impact of this service on
pharmacists' counseling behavior for tobacco cessation.
PMID- 24352811
TI - Human hand transplants and challenges for adaptation in Japan.
PMID- 24352810
TI - Epidemiology of candidemia in Qatar, the Middle East: performance of MALDI-TOF MS
for the identification of Candida species, species distribution, outcome, and
susceptibility pattern.
AB - INTRODUCTION: Bloodstream infections (BSIs) due to Candida spp. constitute the
predominant group of hospital-based fungal infections worldwide. A retrospective
study evaluated the performance of matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of BSI
Candida isolates. The epidemiology, risk factors, demographic features, species
distribution, and clinical outcome associated with candidemia in patients
admitted to a single tertiary-care hospital in Qatar, were analyzed. METHODS: A
single-center, retrospective analysis covering the period from January 1, 2004 to
December 31, 2010 was performed. Molecular identification used sequence analysis
of the D1/D2 domains of the large subunit ribosomal DNA (LSU rDNA) and the ITS1/2
regions of the rDNA. MALDI-TOF MS-based identification of all yeast isolates was
performed with the ethanol/formic acid extraction protocol according to Bruker
Daltonics (Bremen, Germany). The susceptibility profiles of 201 isolates to
amphotericin B, itraconazole, fluconazole, voriconazole, anidulafungin,
caspofungin, posaconazole, and isavuconazole were tested using CLSI standard
broth microdilution method (M27-A3 and M27 S4) guidelines. Statistical analyses
were performed with the statistical package SPSS 19.0. RESULTS: A total of 187
patients with 201 episodes of candidemia were identified. Candida albicans was
the most common species isolated (33.8 %; n = 68), whereas non-albicans Candida
species represented 66.2 % (n = 133) of the episodes. The species distribution
and outcome of candidemia showed a difference in the crude mortality between
patients infected with C. albicans (n = 30; 45.5 %) and non-albicans Candida
species. For example, C. parapsilosis candidemia was associated with the lowest
mortality rate (40.6 %), and patients with other non-albicans species had the
highest mortality rate (68-71.4 %). High mortality rates were observed among
pediatric (<1 year of age) and elderly patients (>60 years of age). All strains
showed low minimum inhibitory concentrations (MICs) (MIC90 of 0.063 MUg/ml) to
isavuconazole. The overall resistance to voriconazole in vitro antifungal
activity was 2.5 %. C. glabrata (n = 38) had an MIC90 of 8 MUg/ml for
fluconazole. Most yeast isolates were susceptible to anidulafungin (>99.5 %) and
81.1 % to caspofungin. Resistance to anidulafungin was detected in 1/8 (12.5 %)
isolates of C. orthopsilosis. According to new Clinical and Laboratory Standards
Institute (CLSI) breakpoints, C. glabrata (n = 38) showed 100 % resistance, and
37/68 (54.4 %) C. albicans isolates were susceptible dose dependent (SDD) to
caspofungin. Identification by MALDI-TOF MS was in 100 % concordance with
molecular identification. CONCLUSION: The Middle East epidemiology of candidemia
has a unique species distribution pattern distinct from other parts of the globe.
High mortality rates were observed among pediatric (<1 year of age) and elderly
patients (>60 years of age). All strains were susceptible to isavuconazole. All
isolates of C.glabrata were resistant to caspofungin based on M27 S4. MALDI-TOF
MS is a highly useful method for the routine identification of yeast isolates in
clinical setting to achieve successful therapeutic treatment.
PMID- 24352813
TI - Reconstruction of large mandibulofacial defects with the composed double skin
paddle fibula free flap: a review of 32 procedures.
AB - OBJECTIVES/HYPOTHESIS: The purpose of this study was to analyze our experience
with the composed double skin paddle fibula free flap to reconstruct large
mandibulofacial defects. STUDY DESIGN: Between 2006 and 2011, a total of 32
composed double skin paddle fibula free flap procedures were performed on 32
patients (mean age 54.4 +/- 9.7 years, mean follow-up period of 3.4 +/- 1.7
years). METHODS: A chart review was drawn up to determine the type of defects
covered by each skin paddle, the vascular anatomy, the origin of the perforators,
and any associated complications. RESULTS: The distal septocutaneous skin paddle
(Nakajima type B) was used for the reconstruction of the floor of the mouth in
most cases. The proximal paddle (Nakajima type D) was used for base of the
tongue, mobile tongue, soft palate, internal cheek, inferior lip, and the skin of
the chin and neck. The lateral soleus pedicle arose from the fibular pedicle in
28 cases and directly from the tibial-fibular trunk in four cases. There were two
partial soleus skin paddle losses. Seven complications required revision surgery:
due to a cervical abscess in two cases, due to a hematoma in two cases, due to a
disunion of the second skin paddle leading to an orostoma in two cases, and due
to an exposition of the osteosynthesis material in one case. CONCLUSION: In large
mandibulofacial defects, a second skin paddle raised on the soleus perforators
may be of benefit when reconstructing the soft palate, neck, cheek, or tongue as
the length of its pedicle renders a second free flap unnecessary. LEVEL OF
EVIDENCE: IV.
PMID- 24352814
TI - Self-assembly and (hydro)gelation triggered by cooperative pi-pi and
unconventional C-H...X hydrogen bonding interactions.
AB - Weak C-H...X hydrogen bonds are important stabilizing forces in crystal
engineering and anion recognition in solution. In contrast, their quantitative
influence on the stabilization of supramolecular polymers or gels has thus far
remained unexplored. Herein, we report an oligophenyleneethynylene (OPE)-based
amphiphilic Pt(II) complex that forms supramolecular polymeric structures in
aqueous and polar media driven by pi-pi and different weak C-H...X (X=Cl, O)
interactions involving chlorine atoms attached to the Pt(II) centers as well as
oxygen atoms and polarized methylene groups belonging to the peripheral glycol
chains. A collection of experimental techniques (UV/Vis, 1D and 2D NMR, DLS, AFM,
SEM, and X-Ray diffraction) demonstrate that the interplay between different weak
noncovalent interactions leads to the cooperative formation of self-assembled
structures of high aspect ratio and gels in which the molecular arrangement is
maintained in the crystalline state.
PMID- 24352815
TI - Altered localization of the delta subunit of the GABAA receptor in the thalamus
of alpha4 subunit knockout mice.
AB - The alpha4 subunit of the GABAA receptor (GABAAR) is highly expressed in the
thalamus where receptors containing the alpha4 and delta subunits are major
mediators of tonic inhibition. The alpha4 subunit also exhibits considerable
plasticity in a number of physiological and pathological conditions, raising
questions about the expression of remaining GABAAR subunits when the alpha4
subunit is absent. Immunohistochemical studies of an alpha4 subunit knockout (KO)
mouse revealed a substantial decrease in delta subunit expression in the
ventrobasal nucleus of the thalamus as well as other forebrain regions where the
alpha4 subunit is normally expressed. In contrast, several subunits associated
primarily with phasic inhibition, including the alpha1 and gamma2 subunits, were
moderately increased. Intracellular localization of the delta subunit was also
altered. While delta subunit labeling was decreased within the neuropil, some
labeling remained in the cell bodies of many neurons in the ventrobasal nucleus.
Confocal microscopy demonstrated co-localization of this labeling with an
endoplasmic reticulum marker, and electron microscopy demonstrated increased
immunogold labeling near the endoplasmic reticulum in the alpha4 KO mouse. These
results emphasize the strong partnership of the delta and alpha4 subunit in the
thalamus and suggest that the alpha4 subunit of the GABAAR plays a critical role
in trafficking of the delta subunit to the neuronal surface. The findings also
suggest that previously observed reductions in tonic inhibition in the alpha4
subunit KO mouse are likely to be related to alterations in delta subunit
expression, in addition to loss of the alpha4 subunit.
PMID- 24352817
TI - Menominee perspectives on commercial and sacred tobacco use.
AB - The Menominee Indian Tribe of Wisconsin has the highest smoking rate in the
state. To address the resultant health disparities, the tribe conducted a
qualitative pilot project to examine tobacco use. The findings indicated
mainstream models of addiction did not capture the tribe's context well; the
Indigenist Stress-Coping Model was most applicable. Participants suggested that
Menominee-centric ways of knowing related to commercial and sacred tobacco use
should be included in all levels of prevention as a key strategy. Recommendations
include primary prevention targeted specifically to youth, pregnant women, and
adults who care for children, as well as access to commercial tobacco products.
PMID- 24352816
TI - The discovery of human of GLUD2 glutamate dehydrogenase and its implications for
cell function in health and disease.
AB - While the evolutionary changes that led to traits unique to humans remain
unclear, there is increasing evidence that enrichment of the human genome through
DNA duplication processes may have contributed to traits such as bipedal
locomotion, higher cognitive abilities and language. Among the genes that arose
through duplication in primates during the period of increased brain development
was GLUD2, which encodes the hGDH2 isoform of glutamate dehydrogenase expressed
in neural and other tissues. Glutamate dehydrogenase GDH is an enzyme central to
the metabolism of glutamate, the main excitatory neurotransmitter in mammalian
brain involved in a multitude of CNS functions, including cognitive processes. In
nerve tissue GDH is expressed in astrocytes that wrap excitatory synapses, where
it is thought to play a role in the metabolic fate of glutamate removed from the
synaptic cleft during excitatory transmission. Expression of GDH rises sharply
during postnatal brain development, coinciding with nerve terminal sprouting and
synaptogenesis. Compared to the original hGDH1 (encoded by the GLUD1 gene), which
is potently inhibited by GTP generated by the Krebs cycle, hGDH2 can function
independently of this energy switch. In addition, hGDH2 can operate efficiently
in the relatively acidic environment that prevails in astrocytes following
glutamate uptake. This adaptation is thought to provide a biological advantage by
enabling enhanced enzyme catalysis under intense excitatory neurotransmission.
While the novel protein may help astrocytes to handle increased loads of
transmitter glutamate, dissociation of hGDH2 from GTP control may render humans
vulnerable to deregulation of this enzyme's function. Here we will retrace the
cloning and characterization of the novel GLUD2 gene and the potential
implications of this discovery in the understanding of mechanisms that permitted
the brain and other organs that express hGDH2 to fine-tune their functions in
order to meet new challenging demands. In addition, the potential role of gain-of
function of hGDH2 variants in human neurodegenerative processes will be
considered.
PMID- 24352818
TI - Rates of delay and probability discounting of northern plains American Indians
discounting Indian and majority culture-specific outcomes.
AB - Discounting occurs when the value of an outcome changes because its delivery is
delayed or uncertain. Discounting provides insight into how individuals make
decisions, with rates of discounting being related to a number of behavioral
disorders. In this study, 39 American Indians (AIs), 29 female, were recruited
from the psychology department participant pool at a university in the Northern
Plains to complete an acculturation inventory and delay- and probability
discounting tasks related to money, health care, and education reform. Results
from ANOVAs showed that participants did not differentially discount the delayed
outcomes, but discounted the probabilistic monetary outcomes to a greater extent
than probabilistic outcomes involving education reform, suggesting that
participants were more risk averse with the monetary, than the education,
outcomes. Differences in discounting were not observed as a function of whether
the outcome would occur on or off a tribal reservation. Results from regression
analyses showed that participants' affiliation with the majority culture was also
related to how they discounted probabilistic monetary outcomes. The present study
represents the first attempt to measure probability discounting in AI
participants and is the first to show differences in this type of decision
making. The results, therefore, represent a step forward in understanding when
risk-averse versus risk-prone decisions (i.e., a small but certain outcome vs. a
better but uncertain outcome) may be made, and how those decisions are related to
acculturation in AIs.
PMID- 24352819
TI - The role of explanatory style and negative life events in depression: a cross
sectional study with youth from a North American plains reservation.
AB - In a cross-sectional study, we examined the role of explanatory styles and
negative life events in the depressive experiences of AI youth. Ninetythree AI
youth (49% female, ages 11-14 years) completed surveys assessing for explanatory
style, negative life events, and depressive symptoms. Path analyses indicated
that both the occurrence of negative life events within the past 6 months and a
pessimistic explanatory style predicted more depressive symptoms. However, a
moderation path model provided a superior fit to the data, indicating that the
occurrence of negative life events was more strongly associated with depressive
symptoms for those AI youth with a more pessimistic explanatory style. Findings
are discussed in terms of potential interventions that can promote the well-being
of this understudied and underserved population.
PMID- 24352820
TI - Preferences for mental health treatment options among Alaska Native college
students.
AB - In this study we investigated the mental health treatment preferences held by
Alaska Native (AN) college students regarding treatment type, treatment provider,
and therapy roles. Preferences were compared between AN and Caucasian
participants and also between ANs with high and low identification with their
Indigenous culture. While there were many similarities between groups, some
important differences were found. The results of this study have significant
implications for making mental health treatments more available and culturally
appropriate for ANs.
PMID- 24352821
TI - Total hip replacement with a collarless polished cemented anatomic stem: clinical
and gait analysis results at ten years follow-up.
AB - PURPOSE: The aim of this study was to determine outcomes of total hip replacement
(THR) with the Lemania cemented femoral stem. METHODS: A total of 78 THR patients
were followed and compared to 17 "fit", healthy, elderly and 72 "frail" elderly
subjects without THR, using clinical outcome measures and a portable, in-field
gait analysis device at five and ten years follow-up. RESULTS: Forty-one patients
(53%), mean age 83.4 years, available at ten years follow-up, reported very good
to excellent satisfaction. Mean Harris Hip and Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC) scores were 81.2 and 10.5 points,
respectively, with excellent radiological preservation of proximal femur bone
stock. Spatial and temporal gait parameters were close to the fit group and
better than the frail group. CONCLUSIONS: Lemania THR demonstrated very good,
stable clinical and radiological results at ten years in an older patient group,
comparable to other cemented systems for primary THR. Gait analysis confirmed
good walking performance in a real-life environment.
PMID- 24352823
TI - Effect of pulsed electromagnetic field therapy in patients undergoing total knee
arthroplasty: a randomised controlled trial.
AB - PURPOSE: It has been reported that even one year after total knee arthroplasty
(TKA), a relevant percentage of patients does not attain complete recovery and
indicate unfavourable long-term pain outcome. We compared the clinical outcome of
33 patients undergoing TKA randomly assigned to the control or the pulsed
electromagnetic field group (I-ONE therapy). METHODS: I-ONE therapy was
administered postoperatively four hours per day for 60 days. Patients were
assessed before surgery and then at one, two and six months postoperatively using
international scores. RESULTS: One month after TKA, pain, knee swelling and
functional score were significantly better in the treated compared with the
control group. Pain was still significantly lower in the treated group at the six
month follow-up. Three years after surgery, severe pain and occasional walking
limitations were reported in a significantly lower number of patients in the
treated group. CONCLUSIONS: Advantages deriving from early control of joint
inflammation may explain the maintenance of results at follow-up. I-ONE therapy
should be considered an effective completion of the TKA procedure.
PMID- 24352824
TI - Minimum ten-year results of a 28-mm metal-on-metal bearing in cementless total
hip arthroplasty in patients fifty years of age and younger.
AB - PURPOSE: Concerns have been raised in relation to metal-on-metal (MoM)
articulations with catastrophic soft-tissue reactions due to metal debris. We
reviewed how small head MoM articulations perform in primary uncemented total hip
arthroplasty (THA) in young patients at a minimum of ten years. METHODS: We
retrospectively evaluated the clinical and radiographic results of the first 100
consecutive primary cementless THAs using the 28-mm Metasul MoM articulation in
91 patients younger than 50 years of age at the time of surgery. RESULTS: After
13 years, survival for the endpoint revision due to any reason was 90.9 % and
98.9 % for revision due to aseptic implant loosening. The cumulative incidence of
MoM related revisions was 1.2 %. Small proximal femoral osteolysis was found in
18 % of hips. No acetabular osteolysis or loosening was detected. Two hips showed
signs of femoral neck impingement with severe damage to the neck. CONCLUSIONS:
Early in the second decade, MoM-associated complications were rare using the 28
mm Metasul articulation, and aseptic loosening was not a major mode of failure in
this cohort of young patients. LEVEL OF EVIDENCE: Therapeutic Level IV.
PMID- 24352822
TI - The clinical use of bone morphogenetic proteins revisited: a novel biocompatible
carrier device OSTEOGROW for bone healing.
AB - PURPOSE: The purpose of this study was to revise the clinical use of commercial
BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of
action and efficacy of low BMP6 doses in a novel whole blood biocompatible device
OSTEOGROW. METHODS: Complications from the clinical use of BMP2 and BMP7 have
been systemically reviewed in light of their role in bone remodeling. BMP6
function has been assessed in Bmp6-/- mice by MUCT and skeletal histology, and
has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells
(HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in
rats and rabbits. RESULTS: Clinical use issues of BMP2 and BMP7 have been
ascribed to the limited understanding of their role in bone remodeling at the
time of device development for clinical trials. BMP2 and BMP7 in bone devices
significantly promote bone resorption leading to osteolysis at the endosteal
surfaces, while in parallel stimulating exuberant bone formation in surrounding
tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen
and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6,
applied in a biocompatible blood coagulum carrier, for stimulating
differentiation of MSCs and accelerated healing of critical size bone defects in
animals, without bone resorption and inflammation. BMP6 decreased the number of
osteoclasts derived from HSC, while BMP2 and BMP7 increased their number.
CONCLUSIONS: Current issues and challenges with commercial bone devices may be
resolved by using novel BMP6 biocompatible device OSTEOGROW, which will be
clinically tested in metaphyseal bone fractures, compartments where BMP2 and BMP7
have not been effective.
PMID- 24352825
TI - The necessity of pharmacological prophylaxis against venous thromboembolism in
major joint arthroplasty.
AB - PURPOSE: Venous thromboembolism (VTE) is a recognised post-operative complication
of major lower limb joint arthroplasty. Current National Institute for Health and
Clinical Excellence (NICE) guidelines suggest the use of both mechanical and
pharmacological prophylaxis following hip and knee replacement. Since the
introduction of enhanced recovery programmes following hip and knee arthroplasty
the requirement for routine pharmacological VTE prophylaxis has been questioned.
The purpose of this study was to assess the efficacy of pharmacological
prophylaxis against symptomatic VTE in patients undergoing hip and knee
arthroplasty under an enhanced recovery programme. METHODS: Symptomatic VTE
incidence was audited in 1,100 patients undergoing primary or revision total hip
or knee arthroplasty at the same hospital with only mechanical prophylaxis from
2007 to 2009. Following addition of chemical prophylaxis (enoxaparin) symptomatic
VTE incidence in 522 patients undergoing primary or revision total hip or knee
arthroplasty from 2011 to 2012 was re-audited. RESULTS: In the mechanical
prophylaxis group incidence of DVT was 0.73 % [95 % confidence interval (CI) 0.37
1.43 %] and incidence of pulmonary embolism (PE) 0.91 % (95 % CI 0.49-1.67 %).
Following addition of pharmacological prophylaxis incidence of DVT was 0.57 % (95
% CI 0.20-1.68 %) and incidence of PE 1.15 % (95 % CI 0.53-2.48 %). CONCLUSIONS:
We found no statistically significant difference in symptomatic VTE incidence
following the addition of enoxaparin. We question whether routine pharmacological
prophylaxis still has a role following total hip and knee arthroplasty. Peri
operative optimisation, including post-operative analgesia and mobility, with
current enhanced recovery programmes may be sufficient. As anticoagulants carry
increased risk of post-operative bleeding and wound ooze, in addition to
significant cost implications, their role remains controversial.
PMID- 24352826
TI - Reply to comment on Lan et al.: S-osteotomy with lengthening and then nailing
compared with traditional Ilizarov method.
PMID- 24352827
TI - [Peroral endoscopic myotomy for treatment of achalasia. Literature review and own
initial experience].
AB - Peroral endoscopic myotomy (POEM) is a new, purely endoscopic procedure for
treatment of achalasia. Due to the lack of incisions POEM can be regarded as a
true NOTES procedure. With POEM a myotomy is created in a similar fashion to the
previous standard treatment, laparoscopic Heller myotomy (LHM). The relatively
free choice of length and localization of the myotomy may be regarded as
advantages of POEM. The procedure starts with a mucosal incision (mucosal entry)
followed by preparation of a submucosal tunnel crossing the esophagogastric
junction and creation of a myotomy in an antegrade direction before the mucosal
access is closed with endoscopic clip placement. Since the first description of
the application of POEM in humans in 2010 by the pioneer Haruhiro Inoue,
Yokohama, Japan, it has been used increasingly and investigated in some centers
in Asia, the U.S.A. and also Europe. The results are very promising. Although the
procedure is technically demanding it can be performed safely with low
complication rates. The POEM procedure achieves very good control of dysphagia
and gastroesophageal reflux witch is only a rare side-effect witch is well
controllable with proton pump inhibitors (PPI). We review the currently available
data from the literature and present our own initial series of 14 patients
treated with POEM.
PMID- 24352828
TI - [Initial experiences with an ERAS protocol in esophageal surgery].
PMID- 24352829
TI - Toxicological effects of the sunscreen UV filter, benzophenone-2, on planulae and
in vitro cells of the coral, Stylophora pistillata.
AB - Benzophenone-2 (BP-2) is an additive to personal-care products and commercial
solutions that protects against the damaging effects of ultraviolet light. BP-2
is an "emerging contaminant of concern" that is often released as a pollutant
through municipal and boat/ship wastewater discharges and landfill leachates, as
well as through residential septic fields and unmanaged cesspits. Although BP-2
may be a contaminant on coral reefs, its environmental toxicity to reefs is
unknown. This poses a potential management issue, since BP-2 is a known endocrine
disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the
larval form (planula) of the coral, Stylophora pistillata, as well as its
toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are
exacerbated in the light versus in darkness. Whether in darkness or light, BP-2
induced coral planulae to transform from a motile planktonic state to a deformed,
sessile condition. Planulae exhibited an increasing rate of coral bleaching in
response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals,
exhibiting a strong positive relationship between DNA-AP lesions and increasing
BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in
both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness
induced autophagy and autophagic cell death.The LC50 of BP-2 in the light for an
8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion
(ppb), respectively. The LC50s for BP-2 in darkness for the same time points were
144 parts per million and 548 parts per billion [corrected].
PMID- 24352830
TI - Imidacloprid affects the functional response of predator Podisus nigrispinus
(Dallas) (Heteroptera: Pentatomidae) to strains of Spodoptera frugiperda (J.E.
Smith) on Bt cotton.
AB - Podisus nigrispinus (Dallas) (Heteroptera: Pentatomidae) is one of the most
common asopine species in the neotropical region and its occurrence was reported
in several countries of South and Central America, as an important biological
control agent for many crops. This study was carried out to identify the
imidacloprid impacts on the functional response of predator P. nigrispinus fed on
Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) strain resistant to
lambda-cyhalothrin, on Bt cotton expressing Cry1Ac (Bollgard((r))). Spodoptera
frugiperda larvae were used in the following conditions: resistant (1) and
susceptible (2) strains to lambda-cyhalothrin fed on Bollgard((r)) cotton leaves
(DP 404 BG); and resistant (3) and susceptible (4) strains to lambda-cyhalothrin
fed on non-genetically modified cotton leaves (cultivar DP4049). The predatory
behavior of P. nigrispinus was affected by imidacloprid and the type II
asymptotic curve was the one that best described the functional response data.
Handling time (T h ) of predator females did not differ among treatments in the
presence of imidacloprid. The attack rate did decrease, however, due to an
increase in the density of larvae offered. Regardless of the treatment (S.
frugiperda strain or cotton cultivar), the predation of P. nigrispinus females on
S. frugiperda larvae was significantly lower when exposed to imidacloprid,
especially at a density of 16 larvae/predator. The predation behavior of P.
nigrispinus on S. frugiperda larvae is affected by the insecticide imidacloprid
showing that its applications should be used in cotton crop with caution.
PMID- 24352832
TI - Effect of diet on type 2 diabetes mellitus: a review.
AB - Type 2 diabetes mellitus is one of the fastest growing diseases; the number of
people affected by diabetes will soon reach 552 million worldwide, with
associated increases in complications and healthcare expenditure. Lifestyle and
medical nutrition therapy are considered the keystones of type 2 diabetes
prevention and treatment, but there is no definite consensus on how to treat this
disease with these therapies. The American Diabetes Association has made several
recommendations regarding the medical nutrition therapy of diabetes; these
emphasize the importance of minimizing macrovascular and microvascular
complications in people with diabetes. Four types of diets were reviewed for
their effects on diabetes: the Mediterranean diet, a low-carbohydrate/high
protein diet, a vegan diet and a vegetarian diet. Each of the four types of diet
has been shown to improve metabolic conditions, but the degree of improvement
varies from patient to patient. Therefore, it is necessary to evaluate a
patient's pathophysiological characteristics in order to determine the diet that
will achieve metabolic improvement in each individual. Many dietary regimens are
available for patients with type 2 diabetes to choose from, according to personal
taste and cultural tradition. It is important to provide a tailor-made diet
wherever possible in order to maximize the efficacy of the diet on reducing
diabetes symptoms and to encourage patient adherence. Additional randomized
studies, both short term (to analyse physiological responses) and long term,
could help reduce the multitude of diets currently recommended and focus on a
shorter list of useful regimens.
PMID- 24352833
TI - Recombinant human lactoferrin as a biomaterial for bone tissue engineering:
mechanism of antiapoptotic and osteogenic activity.
AB - Lactoferrin is a bioactive globular protein with unique properties towards
musculo-skeletal cells and anabolic to bone in vivo. Even though the potent anti
apoptotic and osteogenic activity of lactoferrin has been reported, the mechanism
of action has not been fully elucidated. The study demonstrates that the anti
apoptotic effect of rhLF towards MC3T3 pre-osteoblast cells is mediated by
Wnt5a/PKA pathway and the stabilization of beta-catenin by rhLF is dependent on
PKA/LRP6 signaling pathway. The study also investigates the feasibility of
developing rhLF as a biomaterial for cell delivery. The injectable rhLF cell
delivery vehicles are prepared by enzymatic crosslinking of tyramine-modified
rhLF in the presence of hydrogen peroxide and horseradish peroxidase. The
modified rhLF shows bioactivity similar to unmodified rhLF. The rhLF gels support
encapsulated MC3T3 cell viability, proliferation, and differentiation, as well as
phosphorylation of signaling proteins. In conclusion, the study demonstrates the
involvement of Wnt5a, LRP6, and PKA signaling in rhLF-mediated bioactivity
towards MC3T3 cells and the feasibility of developing an injectable cell delivery
vehicle from rhLF.
PMID- 24352834
TI - Light-emitting Ga-oxide nanocrystals in glass: a new paradigm for low-cost and
robust UV-to-visible solar-blind converters and UV emitters.
AB - Wide-bandgap nanocrystals are an inexhaustible source of tuneable functions
potentially addressing most of the demand for new light emitting systems.
However, the implementation of nanocrystal properties in real devices is not
straightforward if a robust and stable optical component is required as a final
result. The achievement of efficient light emission from dense dispersions of Ga
oxide nanocrystals in UV-grade glass can be a breakthrough in this regard. Such a
result would permit the fabrication of low cost UV-to-visible converters for
monitoring UV-emitting events on a large-scale - from invisible hydrogen flames
to corona dispersions. From this perspective, gamma-Ga2O3 nanocrystals are
developed by phase separation in Ga-alkali-germanosilicate glasses, obtaining
optical materials based on a UV transparent matrix. Band-to-band UV-excitation of
light emission from donor-acceptor pair (DAP) recombination is investigated for
the first time in embedded gamma-Ga2O3. The analysis of the decay kinetics gives
unprecedented evidence that nanosized confinement of DAP recombination can force
a nanophase to the efficient response of exactly balanced DAPs. The results,
including a proof of concept of UV-to-visible viewer, definitely demonstrate the
feasibility of workable glass-based fully inorganic nanostructured materials with
emission properties borrowed from Ga2O3 single-crystals and tailored by the
nanocrystal size.
PMID- 24352841
TI - The incidence and clinical symptomatology of Clostridium difficile infections in
a community setting in a cohort of Danish patients attending general practice.
AB - Clostridium difficile infection (CDI) is gradually being recognised as a cause of
morbidity in the community. We investigated the incidence and clinical
characteristics of CDI in a community setting and characterised the C. difficile
strains by toxin gene profiling and polymerase chain reaction (PCR) ribotyping.
Patients included in the study had attended general practice, primarily because
of diarrhoea; CDI patients (259 patients; 121 <2 years of age) had positive
cultures for toxigenic C. difficile and non-CDI patients (455 patients) were
culture-negative. Outcome variables included the frequency and duration of
diarrhoea, vomiting, stomach ache, fever >38 degrees C, weight loss and sick
leave. Data were analysed by logistic regression. CDI patients <2 and >=2 years
of age with C. difficile as the only enteropathogen in the faecal sample reported
slimy stools (65% vs. 62%), stomach ache (60% vs. 75%), weight loss (50% vs. 76%)
and duration of diarrhoea >15 days (59% vs. 73%) as the predominant symptoms. CDI
patients >=2 years old reported duration of diarrhoea >15 days more often
compared to non-CDI patients (73% vs. 27 %, p < 0.0001). The annual incidence of
CDI was 518 and 23/100,000 for patients <2 and >=2 years of age, respectively,
and 46/100,000 in the subgroup of patients >=60 years of age. CDI was
characterised by stomach ache and persistent diarrhoea, often leading to weight
loss. This emphasises the importance of diagnosing CDI not only in hospitalised
patients, but also in individuals >=2 years of age attending general practice
because of gastrointestinal symptoms, especially in the elderly, where the
incidence of CDI is high.
PMID- 24352842
TI - Assessment of bias in outcomes reported in trials on pneumonia: a systematic
review.
AB - Subjective outcomes may exaggerate intervention effects compared to objectively
measured outcomes. We compared effect estimates for clinical failure and all
cause mortality clinical trials of antibiotic treatment for pneumonia. A
systematic review of randomized controlled trials assessing adults with
pneumonia, comparing different antibiotics, published between 2005 and 2012 was
undertaken. We compared the intervention to the control arm. The all-cause
mortality in the intention-to-treat population and clinical failure as defined by
the study investigators for the primary analyzed population were the primary
outcomes examined. Risk ratios (RRs) with 95 % confidence intervals (CIs) were
pooled, using a fixed effect model. Meta-regression was used to examine the
impact of clinical failure on the mortality effect size. Thirty-six trials were
included, of which 30 were industry-sponsored and 30 were non-inferiority trials.
There was no difference between the effect on mortality for intervention versus
control (RR 1.02, 95 % CI 0.91-1.16) and clinical failure (RR 1.01, 95 % CI 0.93
1.10), without significant heterogeneity in both analyses. In double-blind trials
with adequate sequence generation and concealment, there was a significant
advantage to the intervention for clinical failure (RR 0.86, 95 % CI 0.76-0.98),
but not for mortality (RR 0.96, 95 % CI 0.76-1.21). RRs for clinical failure did
not explain the variability in the RRs for mortality significantly, with a meta
regression coefficient of 0.32 (95 % CI -0.21-0.85). In non-inferiority trials of
antibiotic treatment for pneumonia, we did not find evidence for bias induced by
the use of a subjective outcome overall. The small number of trials without
sponsorship precludes an adequate assessment of sponsorship effects.
PMID- 24352843
TI - Bottom-up and top-down herbivore regulation mediated by glucosinolates in
Brassica oleracea var. acephala.
AB - Quantitative differences in plant defence metabolites, such as glucosinolates,
may directly affect herbivore preference and performance, and indirectly affect
natural enemy pressure. By assessing insect abundance and leaf damage rate, we
studied the responses of insect herbivores to six genotypes of Brassica oleracea
var. acephala, selected from the same cultivar for having high or low foliar
content of sinigrin, glucoiberin and glucobrassicin. We also investigated whether
the natural parasitism rate was affected by glucosinolates. Finally, we assessed
the relative importance of plant chemistry (bottom-up control) and natural enemy
performance (top-down control) in shaping insect abundance, the ratio of
generalist/specialist herbivores and levels of leaf damage. We found that high
sinigrin content decreased the abundance of the generalist Mamestra brassicae
(Lepidoptera, Noctuidae) and the specialist Plutella xylostella (Lepidoptera,
Yponomeutidae), but increased the load of the specialist Eurydema ornatum
(Hemiptera, Pentatomidae). Plants with high sinigrin content suffered less leaf
injury. The specialist Brevicoryne brassicae (Hemiptera, Aphididae) increased in
plants with low glucobrassicin content, whereas the specialists Pieris rapae
(Lepidoptera, Pieridae), Aleyrodes brassicae (Hemiptera, Aleyrodidae) and
Phyllotreta cruciferae (Coleoptera, Chrysomelidae) were not affected by the plant
genotype. Parasitism rates of M. brassicae larvae and E. ornatum eggs were
affected by plant genotype. The ratio of generalist/specialist herbivores was
positively correlated with parasitism rate. Although both top-down and bottom-up
forces were seen to be contributing, the key factor in shaping both herbivore
performance and parasitism rate was the glucosinolate concentration, which
highlights the impact of bottom-up forces on the trophic cascades in crop
habitats.
PMID- 24352844
TI - Invasive clonal plant species have a greater root-foraging plasticity than non
invasive ones.
AB - Clonality is frequently positively correlated with plant invasiveness, but which
aspects of clonality make some clonal species more invasive than others is not
known. Due to their spreading growth form, clonal plants are likely to experience
spatial heterogeneity in nutrient availability. Plasticity in allocation of
biomass to clonal growth organs and roots may allow these plants to forage for
high-nutrient patches. We investigated whether this foraging response is stronger
in species that have become invasive than in species that have not. We used six
confamilial pairs of native European clonal plant species differing in invasion
success in the USA. We grew all species in large pots under homogeneous or
heterogeneous nutrient conditions in a greenhouse, and compared their nutrient
foraging response and performance. Neither invasive nor non-invasive species
showed significant foraging responses to heterogeneity in clonal growth organ
biomass or in aboveground biomass of clonal offspring. Invasive species had,
however, a greater positive foraging response in terms of root and belowground
biomass than non-invasive species. Invasive species also produced more total
biomass. Our results suggest that the ability for strong root foraging is among
the characteristics promoting invasiveness in clonal plants.
PMID- 24352845
TI - Temperature and rainfall strongly drive temporal growth variation in Asian
tropical forest trees.
AB - Climate change effects on growth rates of tropical trees may lead to alterations
in carbon cycling of carbon-rich tropical forests. However, climate sensitivity
of broad-leaved lowland tropical trees is poorly understood. Dendrochronology
(tree-ring analysis) provides a powerful tool to study the relationship between
tropical tree growth and annual climate variability. We aimed to establish
climate-growth relationships for five annual-ring forming tree species, using
ring-width data from 459 canopy and understory trees from a seasonal tropical
forest in western Thailand. Based on 183/459 trees, chronologies with total
lengths between 29 and 62 years were produced for four out of five species.
Bootstrapped correlation analysis revealed that climate-growth responses were
similar among these four species. Growth was significantly negatively correlated
with current-year maximum and minimum temperatures, and positively correlated
with dry-season precipitation levels. Negative correlations between growth and
temperature may be attributed to a positive relationship between temperature and
autotrophic respiration rates. The positive relationship between growth and dry
season precipitation levels likely reflects the strong water demand during leaf
flush. Mixed-effect models yielded results that were consistent across species: a
negative effect of current wet-season maximum temperatures on growth, but also
additive positive effects of, for example, prior dry-season maximum temperatures.
Our analyses showed that annual growth variability in tropical trees is
determined by a combination of both temperature and precipitation variability.
With rising temperature, the predominantly negative relationship between
temperature and growth may imply decreasing growth rates of tropical trees as a
result of global warming.
PMID- 24352849
TI - Clinical trial evidence and use of fish oil supplements.
PMID- 24352851
TI - [In Process Citation].
PMID- 24352850
TI - Pain hypervigilance is associated with greater clinical pain severity and
enhanced experimental pain sensitivity among adults with symptomatic knee
osteoarthritis.
AB - BACKGROUND: Pain hypervigilance is an important aspect of the fear-avoidance
model of pain that may help explain individual differences in pain sensitivity
among persons with knee osteoarthritis (OA). PURPOSE: The purpose of this study
was to examine the contribution of pain hypervigilance to clinical pain severity
and experimental pain sensitivity in persons with symptomatic knee OA. METHODS:
We analyzed cross-sectional data from 168 adults with symptomatic knee OA.
Quantitative sensory testing was used to measure sensitivity to heat pain,
pressure pain, and cold pain, as well as temporal summation of heat pain, a
marker of central sensitization. RESULTS: Pain hypervigilance was associated with
greater clinical pain severity, as well as greater pressure pain. Pain
hypervigilance was also a significant predictor of temporal summation of heat
pain. CONCLUSIONS: Pain hypervigilance may be an important contributor to pain
reports and experimental pain sensitivity among persons with knee OA.
PMID- 24352852
TI - Safe stapling technique for pulmonary vessels with the shortened introducers and
curved tips in thoracoscopic surgery.
AB - Endo GIA(TM) curved tips with Tri-Stapler(TM) is more useful for the approach for
pulmonary vessels than conventional straight staplers. Unless adequate space is
maintained below the vessels, there is a risk of causing damage to the back of
vessels with the curved tip without optional introducers. The recommended method
involves passing silk thread through the back of the pulmonary vessels and
ligating the thread to the introducer. However, the long introducer often applies
tension to pulmonary vessels and can be caught in the tissues surrounding
vessels. Therefore, we devised a new method. First, the introducer is shortened
to a length of approximately 3 cm and attached to a curved tip. Second, a Penrose
drain is passed through the back of the vessels. Last, the introducer is inserted
into the drain and the stapler is guided. The vessels can be cut without removing
the introducers and Penrose drains from staplers.
PMID- 24352853
TI - High-power electrochemical energy storage system employing stable radical
pseudocapacitors.
AB - The development of electrical energy storage devices that can operate at high
charge and discharge rates is fundamentally important, however although
electrochemical capacitors (ECs) can charge and discharge at high rates, their
electrochemical storage capacity remains an order of magnitude lower than that of
conventional lithium-ion batteries. Novel pseudocapasitors are developed, based
on the stable persilyl-susbtituted free radicals of the heavy group 14 elements,
(tBu2 MeSi)3 E(.) [E=Si (1), Ge (2), and Sn (3)], as anode materials for energy
storage system. Such systems showed a remarkable cycle stability without
significant loss of power density, in comparison with similar characteristics of
the known organic radical batteries, the dual carbon cell, and the
electrochemical capacitor. Particularly important is that these novel
electrochemical energy storage systems employing stable heavy group 14 element
radicals are lithium-free. The electrochemical properties and structures of the
reduced and oxidized species were studied by the cyclic voltammetry (CV),
electron paramagnetic resonance (EPR) spectroscopy, and X-ray diffraction (XRD).
PMID- 24352854
TI - Does abnormal interhemispheric inhibition play a role in mirror dystonia?
AB - The presence of mirror dystonia (dystonic movement induced by a specific task
performed by the unaffected hand) in the dominant hand of writer's cramp patients
when the nondominant hand is moved suggests an abnormal interaction between the 2
hemispheres. In this study we compare the level of interhemispheric inhibition
(IHI) in 2 groups of patients with writer's cramp, one with the presence of a
mirror dystonia and the other without as well as a control group. The level of
bidirectional IHI was measured in wrist muscles with dual-site transcranial
magnetic stimulation with a 10-millisecond (short IHI) and a 40-millisecond (long
IHI) interstimulus interval during rest and while holding a pen in 9 patients
with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of
patients without mirror dystonia did not differ from the controls in their IHI
level. In contrast, IHI was significantly decreased in the group of patients with
mirror dystonia in comparison with the group without mirror dystonia and the
controls in both wrist muscles of both the dystonic and unaffected hand whatever
the resting or active condition (P = 0.001). The decrease of IHI level in the
group of patients with mirror dystonia was negatively correlated with the
severity and the duration of the disease: the weaker the level of IHI, the more
severe was the disease and the longer its duration. Interhemispheric inhibition
disturbances are most likely involved in the occurrence of mirror dystonia. This
bilateral deficient inhibition further suggests the involvement of the unaffected
hemisphere in the pathophysiology of unilateral dystonia.
PMID- 24352855
TI - Selective stabilization of ribose by borate.
AB - In this study, borate was found to selectively increase the stability of ribose
over other aldopentoses. Ribose is the only sugar present in both early RNA-based
biochemistry and contemporary DNA-based life, and the stability of ribose is of
fundamental concern for determining the origin of early RNA-based biochemistry.
The formose reaction is a potential process in the prebiotic synthesis of ribose
and its stereoisomers arabinose, xylose, and lyxose. Ribose is the least stable
of these aldopentoses, raising the fundamental question of whether it was
originally a component of primitive RNA or was selected through biotic processes.
Borate is known to increase the stability of aldopentoses, but the specific
differences in the stabilization achieved among different stereoisomers remain
unclear. In this study, it was found that the stabilities of all of the tested
pentoses increased with the concentration of added borate, but notably, the
stability of ribose increased the most. The predominant formation of complexes
between borate and ribose was verified, in agreement with previous studies. This
borate complex formation might have sequestered ribose from the isomerization and
decomposition reactions, resulting in its selective stabilization. These findings
indicate that ribose could have accumulated in borate-rich environments on the
early Earth and suggest that ribose-based nucleotides combined with phosphate and
nucleobases formed abiotically.
PMID- 24352856
TI - Overexpression of SIRT1 in vascular smooth muscle cells attenuates angiotensin II
induced vascular remodeling and hypertension in mice.
AB - Angiotensin II (AngII) induces the development of vascular hypertrophy and
hypertension. We have shown previously that overexpression of class III
deacetylase SIRT1 inhibits AngII-induced hypertrophy in vascular smooth muscle
cells (VSMCs). However, the direct role of SIRT1 in VSMCs in response to AngII
infusion in vivo remains unclear. Here, we found that the expression and activity
of SIRT1 in mouse aortas was decreased significantly by AngII infusion. VSMC
specific SIRT1 transgene (SV-Tg) prevented the increase in systolic blood
pressure (SBP) caused by AngII infusion without affecting heart function in mice.
SIRT1 overexpression alleviated vascular remodeling in mouse thoracic and renal
aortas induced by AngII infusion, and significantly inhibited reactive oxygen
species (ROS) generation, vascular inflammation, and collagen synthesis in
arterial walls. Reduced expression of transforming growth factor-beta 1 (TGF
beta1) was also observed in the aortas of AngII-infused SV-Tg mice. Moreover,
SIRT1 overexpression decreased AngII-increased binding of nuclear factor-kappaB
on its specific binding sites on TGF-beta1 promoter. Taken together, these data
demonstrate that SIRT1 overexpression in VSMCs reduces SBP and inhibits AngII
induced vascular remodeling in mice. The inhibition of vascular remodeling
contributes, at least in part, to the antihypertensive effect of SIRT1. KEY
MESSAGE: SIRT1 is reduced in aortas of AngII-infused hypertensive mice. SIRT1
VSMC transgene alleviates AngII-increased systolic blood pressure. SIRT1 VSMC
transgene attenuates AngII-induced vascular remodeling. VSMC SIRT1 overexpression
inhibits remodeling-related pathological changes. VSMC SIRT1 overexpression
reduces AngII-induced TGF-beta1 expression.
PMID- 24352858
TI - Graphene-based patterning and differentiation of C2C12 myoblasts.
AB - This study aims at generating highly aligned functional myotubes using graphene
as the underlying scaffold. Graphene not only supports the growth of C2C12 muscle
cells but also enhances its differentiation and leads to spontaneous patterning
of myotubes.
PMID- 24352859
TI - Nitrogen removal and microbial communities in a three-stage system simulating a
riparian environment.
AB - The riparian zone is an active interface for nitrogen removal, in which nitrogen
transformations by microorganisms have not been valued. In this study, a three
stage system was constructed to simulate the riparian zone environments, and
nitrogen removal as well as the microbial community was investigated in this
'engineered riparian system'. The results demonstrated that stage 1 of this
system accounted for 41-51 % of total nitrogen removal. Initial ammonium loading
and redox potential significantly impacted the nitrogen removal performances.
Stages 1 and 2 were both composed of an anoxic/oxic (A/O) zone and an anaerobic
column. The A/O zone removed most of the ammonium load (6.8 g/m(2)/day), while
the anaerobic column showed a significant nitrate removal rate (11.1 g/m(2)/day).
Molecular biological analysis demonstrated that bacterial diversity was high in
the A/O zones, where ammonium-oxidizing bacteria and nitrite-oxidizing bacteria
accounted for 8.42 and 3.32 % of the bacterial population, respectively. The
denitrifying bacteria Acidovorax sp. and the nitrifying bacteria
Nitrosospira/Nitrosomonas were the predominant microorganisms in this engineered
riparian system. This three-stage system was established to achieve favorable
nitrogen removal and the microbial community in the system was also retained.
This investigation should deepen our understanding of biological nitrogen removal
in engineered riparian zones.
PMID- 24352860
TI - Optimization of exopolysaccharide production in submerged culture of Daedalea
dickinsii and its antioxidant activity.
AB - The major nutrients, pH and temperature were evaluated for the exopolysaccharide
(EPS) production by Daedalea dickinsii in submerged culture to derive an optimal
medium composition and conditions as follows: 50 g/L maltose, 5 g/L soy peptone,
5 mM CaCl(2), at pH 6.0 and 28 degrees C. A purified EPS fraction was attained
from gel filtration chromatography and its major molecular characteristics were
determined. FT-IR spectral analysis revealed the prominent characteristic groups
of polyhydric alcohols. GC analysis and NMR spectrum showed its major molecular
composition of glucose and galactose. Furthermore, thermogravimetric analysis
indicated its degradation temperature (T(d)) of 189 degrees C. The antioxidant
activity of the EPS fraction showed a correlation with the molecular properties.
It might be attributed to the functional groups in the EPS fraction, which can
donate electrons to reduce the radicals to a more stable form or react with the
free radicals to terminate the radical chain reaction.
PMID- 24352861
TI - Risk factors for systemic air embolism as a complication of percutaneous CT
guided lung biopsy: multicenter case-control study.
AB - PURPOSE: To determine risk factors for systemic air embolism by percutaneous
computed tomography (CT)-guided lung biopsy. METHODS: This case-control study
used data from 2216 percutaneous lung biopsy procedures performed over 11 years
at 12 institutions in Japan. Systemic air embolism was identified by
retrospective review of CT images obtained during and immediately after the
procedures. To fulfill our objective, multiple variables were compared between
cases and controls with univariate analyses by using Student's t test and
Fisher's exact test for numerical and categorical values, respectively.
Multivariate logistic regression analysis was then performed using selected
variables. RESULTS: Ten cases of systemic air embolism and 2,206 controls were
identified. Univariate analyses showed that the lesions in the lower lobe (P =
0.025) and occurrence of parenchymal hemorrhage (P = 0.019) were significant risk
factors. Multivariate analysis showed that the use of a larger biopsy needle was
a significant risk factor (P = 0.014). CONCLUSION: Parenchymal hemorrhage during
the procedure, lesions in the lower lobe, and the use of larger biopsy needles
may be risk factors for systemic air embolism by percutaneous CT-guided lung
biopsy. Our findings may provide clues toward minimizing the risk of this
complication.
PMID- 24352862
TI - Endovascular salvage of a false aneurysm of the posterior tibial artery caused by
a stab from a stingray.
PMID- 24352863
TI - Optimizing needle direction during transjugular liver biopsy provides superior
biopsy specimens.
AB - PURPOSE: Transjugular liver biopsy (TJLB) is commonly performed for staging of
liver fibrosis and cirrhosis among patients with coagulopathy and/or ascites. We
hypothesized that device orientation during needle firing influences hepatic
tissue apposition with the specimen notch and specimen quality. METHODS: Needle
biopsies were performed in ex vivo bovine livers with specimen notch of the
biopsy device oriented at cranial, caudal, or lateral directions with respect to
the guiding metal cannula. Biopsy specimen length was measured and evaluated for
fragmentation using light microscopy. In addition, a consecutive cohort of
patients (n = 50) who underwent TJLB with random (n = 22) or caudal (n = 28)
needle orientation was retrospectively reviewed. The number of needle passes was
documented, and pathology specimen adequacy was graded using an ordinal scale.
RESULTS: A total of 400 biopsies were performed (100 in each orientation) in ex
vivo bovine livers. Longer specimens were obtained with caudal orientation of the
needle specimen notch (p < 0.0001, ANOVA and Kruskal-Wallis tests). There was no
difference in the degree of fragmentation. In the retrospective clinical study,
specimen adequacy was significantly higher among patients in the caudal
orientation group (p = 0.0002, Mann-Whitney U test). CONCLUSION: Caudal
orientation of the needle specimen notch of the biopsy device during TJLB
produces superior core biopsy specimens. This simple technical modification may
assist in obtaining higher-quality biopsy specimens during TJLB.
PMID- 24352864
TI - Right adrenal venography findings correlated with C-arm CT for selection during C
arm CT-assisted adrenal vein sampling in primary aldosteronism.
AB - PURPOSE: This study was designed to evaluate retrospectively the efficacy of C
arm CT to confirm right adrenal vein catheterization during adrenal vein sampling
(AVS) and to correlate adrenal venography findings with C-arm CT and/or
biochemical results for right adrenal vein selection. METHODS: Forty-two
consecutive primary aldosteronism patients (M:F = 21:21; age: 29-70 years)
underwent C-arm CT assisted sequential AVS. After catheterization of right
adrenal vein, C-arm CT was performed to confirm catheter position. Catheter was
repositioned when right adrenal gland was not opacified. Radiological images,
medical records, and biochemical results were reviewed for technical/biochemical
success rates and complications. Right adrenal venography findings of pinnate
pattern, visualization of renal capsular vein, and retroperitoneal vein other
than renal capsular vein were correlated with C-arm CT and/or biochemical results
for right adrenal vein selection. RESULTS: Both the technical and biochemical
success of AVS was achieved in 40 patients (95.2%). C-arm CT failed due to
catheter instability in one, and adrenal/vena cava cortisol gradient was <3 in
one patient. Catheter was repositioned in four patients (9.5%) according to C-arm
CT findings. Right adrenal venography finding of renal capsular vein
significantly correlated with C-arm CT and/or biochemical results (100%) for
right adrenal vein selection (p = 0.011, chi(2) test), whereas pinnate pattern (p
= 0.099) and other retroperitoneal veins (p = 0.347) did not. There was no
procedure-related complication. CONCLUSIONS: C-arm CT increases confidence of
right adrenal vein catheterization during AVS. Visualization of renal capsular
vein on adrenal venography suggests right adrenal vein catheterization and C-arm
CT may not be required.
PMID- 24352865
TI - Embolization of the neck lymphatic varix, causing periodic neck swelling.
AB - We report a case of a 44-year-old female patient, presented to us after years of
recurrent intermittent episodes of unilateral left neck swelling. An MR
lymphangiogram demonstrated a lymphatic varix at the confluence of the left upper
extremity lymphatic ducts, confirmed by intranodal axillary lymphangiography.
After successful catheterization of the feeding lymphatic vessels, the varix was
successfully embolized with detachable microcoils and an autologous blood patch.
The patient has been free from symptoms on subsequent outpatient follow-up.
PMID- 24352866
TI - Highly sensitive electrochemiluminescence determination of etamsylate using a low
cost electrochemical flow-through cell based on a tris(2, 2'
bipyridyl)ruthenium(II)-Nafion-modified carbon paste electrode.
AB - A simple and sensitive electrochemiluminescence (ECL) method for the
determination of etamsylate has been developed by coupling an electrochemical
flow-through cell with a tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)3(2+))-Nafion
modified carbon electrode. It is based on the oxidized Ru(bpy)3(2+) on the
electrode surface reacting with etamsylate and producing an excellent ECL signal.
Under optimized experimental conditions, the proposed method allows the
measurement of etamsylate over the range of 8-1000 ng/mL with a correlation
coefficient of r = 0.9997 (n = 7) and a limit of detection of 1.57 ng/mL
(3sigma), the relative standard deviation (RSD) for 1000 ng/mL etamsylate (n = 7)
is 0.96%. The immobilized Ru(bpy)3(2+) carbon paste electrode shows good
electrochemical and photochemical stability. This method is rapid, simple,
sensitive and has good reproducibility. It has been successfully applied to the
determination of the studied etamsylate in pharmaceutical preparations with
satisfactory results. The possible ECL reaction mechanism has also been
discussed.
PMID- 24352867
TI - Assessing environmentally significant effects: a better strength-of-evidence than
a single P value?
AB - Interpreting a P value from a traditional nil hypothesis test as a strength-of
evidence for the existence of an environmentally important difference between two
populations of continuous variables (e.g. a chemical concentration) has become
commonplace. Yet, there is substantial literature, in many disciplines, that
faults this practice. In particular, the hypothesis tested is virtually
guaranteed to be false, with the result that P depends far too heavily on the
number of samples collected (the 'sample size'). The end result is a swinging
burden-of-proof (permissive at low sample size but precautionary at large sample
size). We propose that these tests be reinterpreted as direction detectors (as
has been proposed by others, starting from 1960) and that the test's procedure be
performed simultaneously with two types of equivalence tests (one testing that
the difference that does exist is contained within an interval of indifference,
the other testing that it is beyond that interval-also known as bioequivalence
testing). This gives rise to a strength-of-evidence procedure that lends itself
to a simple confidence interval interpretation. It is accompanied by a strength
of-evidence matrix that has many desirable features: not only a
strong/moderate/dubious/weak categorisation of the results, but also
recommendations about the desirability of collecting further data to strengthen
findings.
PMID- 24352868
TI - Evaluation of anthropogenic effects on water quality and bacterial diversity in
Rawal Lake, Islamabad.
AB - Water quality and bacterial diversity in the surface water of Rawal Lake was
investigated for a period of 8 months to evaluate the pollution load from
anthropogenic effects of surrounding areas. Rawal Lake in Islamabad, Pakistan is
an artificial reservoir that provides the water needs for the residents of
Rawalpindi and Islamabad. Grabbed water samples were collected according to
standard protocols from ten different locations of the lake and tributaries
keeping in view the recharge points from adjacent areas. Temperature, pH,
electrical conductivity, dissolved oxygen, total dissolved solids, hardness,
alkalinity, and turbidity of water samples were determined to study the water
quality characteristics. The physicochemical parameters showed higher values at
the tributaries as compared to the sampling locations within the lake such as
values of hardness and alkalinity were 298 and 244 mg/L, respectively, at the
tributary of the Nurpur stream. Bacterial strains were isolated by streaking on
differential and selective growth media by observing colony morphology and other
biochemical tests such as Gram reaction, oxidase, and catalase test. Template DNA
was prepared from pure cultivated bacteria and 16S rRNA gene analysis was
performed using universal primers for bacteria. Sequencing was performed by using
BigDye terminator cycle sequencing kit. Sequences of nearest relative microbial
species were identified by using basic local alignment search tool and used as
reference sequences for phylogenetic analysis. Phylogenetic trees were inferred
using the neighbor-joining method. Sequencing and phylogenetic characterization
of microbes showed various phylotypes, of which Firmicutes, Teobacteria, and
Proteobacteria were predominant.
PMID- 24352869
TI - A controlled study of income development for breast cancer survivors in Norway.
AB - AIMS: This study seeks to assess the impact of breast cancer on survivors' annual
income at 1 to 13 years of follow-up. METHODS: A Norwegian registry-based dataset
with a 13-year follow-up period was used. The dataset contained case-control
pairs, where each pair consisted of one breast cancer case and a cancer-free
control, matched for age, marital status, and municipality of residence. A mixed
linear model was used to analyse the average income development for cases and
controls adjusting for available demographic variables not used in the matching
procedure, such as education level, immigration history, and number of children.
Individual income was only considered relevant for cancer survivors, thus case
control pairs were censored upon death. Income development by stage of tumour at
time of diagnosis was also assessed. RESULTS: The income of breast cancer
survivors had reduced immediately following diagnosis. At 1 year after diagnosis,
income development between cases and controls became significantly different (p =
0.006). Differences increased slightly but remained significant throughout the
follow-up period. At 13 years after diagnosis, the estimated cumulative income
loss for survivors was 39.403 ? (p < 0.001). The income development of stage I
breast cancer patients was similar to their controls. For higher stage breast
cancer patients, the income differences were more pronounced but not always
statistically significant. CONCLUSIONS: Breast cancer has a significant negative
effect on the individual incomes of survivors, even at 13 years after diagnosis.
Effects increased for individuals with more advanced cancer stages. IMPLICATIONS
FOR CANCER SURVIVORS: In Norway, breast cancer survivors experience lower income
than their cancer-free controls. This may indicate a need for financial
compensations in order to maintain the standard of living for this group of
patients.
PMID- 24352870
TI - A multidimensional scale to measure the reproductive concerns of young adult
female cancer survivors.
AB - PURPOSE: Concerns about fertility and parenthood are important to many young
adult (YA) female cancer survivors and are associated with poorer quality of
life. We aimed to develop a new scale to comprehensively measure these concerns
so that they can be better addressed. METHODS: Scale development involved: (1)
seven focus groups to identify reproductive concerns among YA female cancer
survivors and develop potential scale items followed by pilot testing and
cognitive interviews to refine items, (2) administering surveys to 204 YA female
survivors and conducting principal components analysis (PCA) with oblique
rotation to identify underlying factors in the multidimensional scale, and (3)
identification of preliminary construct validity evidence. RESULTS: We subjected
37 potential scale items to PCA, which indicated a six-factor solution. After
removing low-loading and cross-loading items, we selected the three top loading
items representing each factor. The 18-item Reproductive Concerns After Cancer
scale (alpha = 0.82) assesses concerns about fertility potential, partner
disclosure, child's health, personal health, acceptance, and becoming pregnant.
As hypothesized, women who wanted to have a baby (p < 0.001) and those for whom
having a biological child was very important (p < 0.05) had higher mean scores,
indicating higher concerns. CONCLUSIONS: The scale demonstrated good internal
consistency and evidence of construct validity and holds promise for future
clinical and research applications. IMPLICATIONS FOR CANCER SURVIVORS: An
effective tool to identify concerns related to fertility and parenthood is
essential for meeting the long-term reproductive health needs of young women who
have survived cancer.
PMID- 24352872
TI - In Situ synthesis of self-assembled gold nanoparticles on glass or silicon
substrates through reactive inkjet printing.
AB - A facile and low cost method for the synthesis of self-assembled nanoparticles
(NPs) with minimal size variation and chemical waste by using reactive inkjet
printing was developed. Gold NPs with diameters as small as (8+/-2) nm can be
made at low temperature (120 degrees C). The size of the resulting NPs can be
readily controlled through the concentration of the gold precursor and oleylamine
ink. The pure gold composition of the synthesized NPs was confirmed by energy
dispersive X-ray spectroscopy (EDXS) analysis. High-resolution SEM (HRSEM) and
TEM (HRTEM), and X-ray diffraction revealed their size and face-centered cubic
(fcc) crystal structure, respectively. Owing to the high density of the NP film,
UV/Vis spectroscopy showed a red shift in the intrinsic plasmonic resonance peak.
We envision the extension of this approach to the synthesis of other
nanomaterials and the production of tailored functional nanomaterials and
devices.
PMID- 24352871
TI - Perspectives of cancer survivors on the role of different healthcare providers in
an integrated delivery system.
AB - PURPOSE: The purpose of this paper is to describe patient perspectives on
survivorship care 1 year after cancer diagnosis. METHODS: The study was conducted
at an integrated healthcare delivery system in western Washington State.
Participants were patients with breast, colorectal, and lung cancer who had
enrolled in a randomized control trial (RCT) of oncology nurse navigation to
improve early cancer care. Those alive and enrolled in the healthcare system 1
year after diagnosis were eligible for this analysis. Participants completed
surveys by phone. Questions focused on receipt of treatment summaries and care
plans; discussions with different providers; patient opinions on who does and
should provide their care; and patient perspectives primary care providers' (PCP)
knowledge and skills related to caring for cancer survivors RESULTS: Of the 251
participants in the RCT, 230 (91.6%) responded to the 12-month phone survey and
were included in this analysis; most (n = 183, 79.6%) had breast cancer. The
majority (84.8%) considered their cancer specialist (e.g., medical, radiation,
surgical or gynecological oncologist) to be their main provider for cancer follow
up and most (69.4%) had discussed follow-up care with that provider.
Approximately half of patients were uncertain how well their PCP communicated
with the oncologist and how knowledgeable s/he was in caring for cancer
survivors. CONCLUSIONS: One year after diagnosis, cancer survivors continue to
view cancer specialists as their main providers and are uncertain about their
PCP's skills and knowledge in managing their care. Our findings present an
opportunity to help patients understand what their PCPs can and cannot provide in
the way of cancer follow-up care. IMPLICATIONS FOR CANCER SURVIVORS: Additional
research on care coordination and delivery is necessary to help cancer survivors
manage their care between primary care and specialty providers.
PMID- 24352873
TI - Oral therapy for onychomycosis: an evidence-based review.
AB - INTRODUCTION: Onychomycosis is a very common fungal infection of the nail
apparatus; however, it is very hard to treat, even when the causative agent is
identified, and usually requires prolonged systemic antifungal therapy. Until the
1990s, oral treatment options included only griseofulvin and ketoconazole, and
the cure rate was very low. New generations of antimycotics, such as fluconazole,
itraconazole and terbinafine have improved treatment success. METHODS: Literature
was identified by performing a PubMed Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL,
and Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS) search.
Prospective and randomized clinical trials were chosen to be included in this
review. Forty-six trials were included. RESULTS: Fluconazole, itraconazole and
terbinafine are effective in the treatment of onychomycosis and have a good
safety profile. When a dermatophyte is the pathogen, terbinafine produces the
best results. For Candida and nondermatophyte infections, the azoles, mainly
itraconazole, are the recommended therapy. CONCLUSION: In the majority of the
studies, terbinafine treatment showed a higher cure ratio than the other drugs
for dermatophyte onychomycosis.
PMID- 24352874
TI - Altered distribution of extracellular matrix proteins in the periodontal ligament
of periostin-deficient mice.
AB - Verifying whether periostin affects the distribution of type I collagen,
fibronectin and tenascin C in the periodontal ligament (PDL) is important to
contribute to a more thorough understanding of that protein's functions. In this
study, we have histologically examined incisor PDL of mandibles in 20 week-old
male wild-type and periostin-deficient (periostin-/-) mice, by means of type I
collagen, fibronectin, tenascin C, proliferating cell nuclear antigen, matrix
metallo-proteinase (MMP)-1 and F4/80-positive monocyte/macrophage immunostaining,
transmission electron microscopy and quantitative analysis of cell proliferation.
Wild-type PDL featured well-arranged layers of collagen bundles intertwined with
PDL cells, whose longitudinal axis ran parallel to the collagen fibers. However,
cells in the periostin-/- PDL were irregularly distributed among collagen
fibrils, which were also haphazardly arranged. Type I collagen and fibronectin
reactivity was seen throughout the wild-type PDL, while in the periostin-/- PDL,
only focal, uneven staining for these proteins could be seen. Similarly, tenascin
C staining was evenly distributed in the wild-type PDL, but hardly seen in the
periostin-/- PDL. MMP-1 immunoreactivity was uniformly distributed in the wild
type PDL, but only dotted staining could be discerned in the periostin-/- PDL.
F4/80-positive monocyte/macrophages were found midway between tooth- and bone
related regions in the wild-type PDL, a pattern that could not be observed in the
periostin-/- PDL. In summary, periostin deficiency may not only cause PDL
collagen fibril disorganization, but could also affect the distribution of other
major extracellular matrix proteins such as fibronectin and tenascin C.
PMID- 24352875
TI - CHELT therapy in the treatment of chronic insertional Achilles tendinopathy.
AB - The application of laser therapy on soft tissue is used for pain relief, anti
inflammation action and biostimulation. The efficiency of High Energy Laser
Therapy has not yet been studied on Achilles tendinopathy. The aim of the study
is to evaluate the effectiveness of a flow of Cold air and High Energy Laser
Therapy (CHELT) versus Extracorporeal Shock Waves Therapy (ESWT) in the treatment
of Achilles tendinopathy. In this prospective, clinical trial, 60 subjects
affected by insertional Achilles tendinopathy were enrolled and randomized to
CHELT (30 subjects) or to ESWT (30 subjects). In CHELT group the patients
received ten daily sessions of 1,200 J and 12 W of laser therapy (wavelength of
1,084, 810 and 980 nm) added to a flow of cold air at -30 degrees C. In the ESWT
group, the patients received three sessions at 3- to 4-day intervals of 1,600
impulses with an energy flux density (EFD) of 0.05-0.07 mJ/mm(2). Both groups of
participants performed stretching and eccentric exercises over a 2-month period.
The visual analogue scale (VAS), the Ankle-Hindfoot Scale, and the Roles and
Maudsley Score were measured before treatment (T0), and at end of the treatment
session (T1) and 2 (T2) and 6 months (T3) after treatment during the follow-up
examinations. In both groups, we found a statistically significant improvement of
the VAS at T1, T2 and T3 (p < 0.01). The difference between the two groups was
statistically significant in favour of the CHELT group (p < 0.001). At 2 months,
the CHELT group was statistically better for Ankle-Hindfoot Scale and the Roles
and Maudsley Score (p < 0.05) and at 6 months only for the Roles and Maudsley
Score (p < 0.001). High Energy Laser Therapy gave quicker and better pain relief.
It also gave the patient a full functional recovery and greater satisfaction.
PMID- 24352876
TI - Evidence for A1 and A 3 receptors mediating adenosine-induced intracellular
calcium release in the dorsal root ganglion neurons by using confocal microscopy
imaging.
AB - Adenosine exerts a key role in analgesia. In the present study, adenosine-induced
Ca(2+) responses were revealed by using confocal microscopy imaging in the rat
dorsal root ganglia (DRG) neurons in vitro. Our results showed that adenosine
could evoke increases in the intracellular Ca(2+) concentration in the DRG
neurons. In addition, by application of selective receptor antagonists, two types
of receptors, A1R and A3R, were identified to be involved in the adenosine
induced Ca(2+) release from intracellular stores in neurons. Altogether, these
results suggest that confocal microscopy imaging combined with fluorescent dyes
could help to detect the analgesic-induced ion signaling in single cell.
PMID- 24352877
TI - Female reproductive factors, menopausal hormone use, and Parkinson's disease.
AB - The objective of this study was to examine the associations of reproductive
factors and exogenous hormone use with risk of Parkinson's disease (PD) among
postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to
71 years in the NIH-AARP Diet and Health Study, who completed a baseline
questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410
self-reported PD diagnoses were identified between 1995 and 2006. Multivariate
odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic
regression models. PD risk was not significantly associated with female
reproductive factors including age at menarche, age at first live birth, parity,
and age at menopause. For example, compared with women with natural menopause at
age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural
menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33
(95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive
use for >=10 years (vs. never used) was associated with lower PD risk (OR, 0.59;
95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal
hormone therapy showed inconsistent results. Compared with non-hormone users at
baseline, current hormone users for <5 years showed a higher risk of PD (OR,
1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone
users or current users of >=5 years. Overall, this large prospective study
provides little support for an association between female reproductive factors
and PD risk. Our findings on long-term oral contraceptive use and current hormone
therapy warrant further investigations.
PMID- 24352878
TI - Lyn-mediated procaspase 8 dimerization blocks apoptotic signaling in B-cell
chronic lymphocytic leukemia.
AB - Lyn, a member of the group of tyrosine kinases named the Src family kinases
(SFKs), is overexpressed, associated with an aberrant multiprotein complex and
constitutively active in B-cell chronic lymphocytic leukemia (B-CLL) cells,
resulting in a high level of tyrosine phosphorylation and contributing to their
resistance to apoptosis. By using biochemical and bioinformatics tools, we
identified procaspase-8 (procasp8), the caspase-8 zymogen, as a cytosolic target
for Lyn in B-CLL cells, the phosphorylation of which at Tyr380 promotes the
formation of an inactive procasp8 homodimer. This complex remains segregated in
the cytosol and appears to be crucial in mediating the antiapoptotic function of
Lyn in this disease. The significance of the Lyn-procasp8 axis in impairing
apoptosis in B-CLL cells was further confirmed by pharmacological and genetic
inhibition of procasp8, which drastically reduced the apoptosis induced by the
SFK inhibitors PP2 and dasatinib. Our data highlight that Lyn's dysregulated
expression, activity, and localization in B-CLLs support resistance to cell
demise by inhibiting an early player of apoptotic signaling, and potentially
broaden the perspectives of developing new strategies for the treatment of this
disease.
PMID- 24352879
TI - A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in
granulocytic differentiation.
AB - We identified diminished levels of the natural inhibitor of neutrophil elastase
(NE), secretory leukocyte protease inhibitor (SLPI), in myeloid cells and plasma
of patients with severe congenital neutropenia (CN). We further found that
downregulation of SLPI in CD34(+) bone marrow (BM) hematopoietic progenitors from
healthy individuals resulted in markedly reduced in vitro myeloid differentiation
accompanied by cell-cycle arrest and elevated apoptosis. Reciprocal regulation of
SLPI by NE is well documented, and we previously demonstrated diminished NE
levels in CN patients. Here, we found that transduction of myeloid cells with
wild-type NE or treatment with exogenous NE increased SLPI messenger RNA and
protein levels, whereas transduction of mutant forms of NE or inhibition of NE
resulted in downregulation of SLPI. An analysis of the mechanisms underlying the
diminished myeloid differentiation caused by reduced SLPI levels revealed that
downregulation of SLPI with short hairpin RNA (shRNA) upregulated nuclear factor
kappaB levels and reduced phospho-extracellular signal-regulated kinase (ERK1/2)
mediated phosphorylation and activation of the transcription factor lymphoid
enhancer-binding factor-1 (LEF-1). Notably, microarray analyses revealed severe
defects in signaling cascades regulating the cell cycle, including c-Myc
downstream signaling, in myeloid cells transduced with SLPI shRNA. Taken
together, these results indicate that SLPI controls the proliferation,
differentiation, and cell cycle of myeloid cells.
PMID- 24352880
TI - Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.
AB - Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to
conventional chemotherapy. Although defined by the characteristic t(11;14)
translocation, MCL has not been recapitulated in transgenic mouse models of
cyclin D1 overexpression alone. Indeed, several genetic aberrations have been
identified in MCL that may contribute to its pathogenesis and chemoresistance. Of
particular interest is the frequent biallelic deletion of the proapoptotic BCL-2
family protein BIM. BIM exerts its pro-death function via its alpha-helical BH3
death domain that has the dual capacity to inhibit antiapoptotic proteins such as
BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the
mitochondrial executioner protein BAX. To evaluate a functional role for Bim
deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice
harboring Bim-deficient B cells. In response to immunization,
EMU(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their
splenic mantle zone compartment. Three distinct immune stimulation regimens
induced lymphomas with histopathologic and molecular features of human MCL in a
subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1
overexpression, disrupts a critical control point in lymphoid maturation and
predisposes to the development of MCL. This genetic proof of concept for MCL
pathogenesis suggests an opportunity to reactivate the death pathway by
pharmacologic mimicry of proapoptotic BIM.
PMID- 24352881
TI - Gender and cell-type-specific effects of the transcription-coupled repair
protein, ERCC6/CSB, on repeat expansion in a mouse model of the fragile X-related
disorders.
AB - The repeat expansion diseases are human genetic disorders that arise from the
expansion of a tandem-repeat tract. The Fragile X-related disorders are members
of this disease group in which the repeat unit is CGG/CCG and is located in the
5' untranslated region of the FMR1 gene. Affected individuals often show
mosaicism with respect to repeat number resulting from both expansion and
contraction of the repeat tract; however, the mechanism responsible for these
changes in repeat number is unknown. The work from a variety of model systems
suggests that transcription-coupled repair (TCR) may contribute to repeat
instability in diseases resulting from CAG/CTG-repeat expansion. To test whether
TCR could contribute to repeat instability in the Fragile X-related disorders, we
tested the effect of mutations in Csb (Cockayne syndrome group B), a gene
essential for TCR, in a knock-in mouse model of these disorders. We found that
the loss of CSB affects expansions in a gender and cell-type-specific manner. Our
data also show an unanticipated gender difference in instability even in Csb+/+
animals that may have implications for our understanding of the mechanism of
repeat expansion in the FX mouse model and perhaps for humans as well.
PMID- 24352883
TI - Hypoxia effects on gill surface area and blood oxygen-carrying capacity of the
Atlantic stingray, Dasyatis sabina.
AB - Atlantic stingrays, Dasyatis sabina, are common residents of shallow-water
seagrass habitats that experience natural cycles of severe hypoxia during summer
months. We hypothesized that stingrays exposed to hypoxic episodes would improve
their hypoxia tolerance by increasing branchial surface area and altering blood
oxygen-carrying capacity. To this end, we compared critical oxygen minimum, gill
morphology, and hemoglobin/hematocrit levels in a control group of Atlantic
stingrays held at continuous oxygen saturations of 80-90% (>=5.5 mg/l), to
treatment groups exposed to a 7-h hypoxic interval at 55% (~4.0 mg/l), or 30%
oxygen saturation (~2.0 mg/l). Stingrays in hypoxic treatment groups
significantly improved their hypoxia tolerance. Critical oxygen minimum values
fell from 0.7 +/- 0.11 mg/l in control fish to 0.4 +/- 0.05 and 0.4 +/- 0.06 mg/l
in the 55 and 30% saturation treatment groups, respectively. Mass-specific gill
surface area between control fish and the 30% saturation treatment group
increased by 1.7-fold, from 85 to 142 mm(2)/g. Although stingrays did not show an
increase in hematocrit or hemoglobin levels, production of more efficient
hemoglobin isoforms could not be ruled out. An increase in hypoxia tolerance
allows Atlantic stingrays to forage for longer times and across a wide range of
hypoxic habitats that are less accessible to predators and competitors.
PMID- 24352884
TI - Bacteriophage polysaccharide depolymerases and biomedical applications.
AB - Polysaccharide depolymerase, a polysaccharide hydrolase encoded by bacteriophages
(or 'phages'), can specifically degrade the macromolecule carbohydrates of the
host bacterial envelope. This enzyme assists the bacteriophage in adsorbing,
invading, and disintegrating the host bacteria. Polysaccharide depolymerase
activity continues even within biofilms. This effectiveness means phages are
promising candidates for novel antibiotic scaffolds. A comprehensive compendium
of bacteriophage polysaccharide depolymerases has been compiled, together with
their potential biomedical applications, such as novel antibiotics, adjuvants for
antibiotics, bacterial biofilm disruptants, and diagnostic kits.
PMID- 24352885
TI - Reply to comments on "synthesis, characterization, and structures of persistent
aniline radical cation".
PMID- 24352886
TI - How does reading performance modulate the impact of orthographic knowledge on
speech processing? A comparison of normal readers and dyslexic adults.
AB - Studies on proficient readers showed that speech processing is affected by
knowledge of the orthographic code. Yet, the automaticity of the orthographic
influence depends on task demand. Here, we addressed this automaticity issue in
normal and dyslexic adult readers by comparing the orthographic effects obtained
in two speech processing tasks that are or not sensitive to strategies developed
by participants. Our finding showed that while participants' performance in a
metaphonological task, which is known to be strategy prone, was affected by their
orthographic knowledge regardless of the childhood diagnosis of dyslexia or of
their actual reading-related skills, this latter factor significantly modulated
the orthographic influence found in a more natural speech recognition task. The
finding supports the claim that while any individuals who know a reading code are
able to resort to their orthographic knowledge when they process speech, a more
profound modification of the speech processing system by the orthographic code
takes place only in readers who have reached a certain level of reading
expertise.
PMID- 24352887
TI - Eyes wide shut: the illusory tale of 'occult' microscopic endometriosis.
PMID- 24352888
TI - Occult microscopic endometriosis: undetectable by laparoscopy in normal
peritoneum.
AB - STUDY QUESTION: Is there any occurrence of hidden (occult) endometriotic lesions
in normal peritoneum of women with and without visible endometriosis? SUMMARY
ANSWER: We detected a slightly higher occurrence of occult microscopic
endometriosis (OME) in normal peritoneum of women with visible endometriosis than
in control women. WHAT IS KNOWN ALREADY: Based on a small number of cases, the
concept of invisible microscopic endometriosis in visually normal peritoneum has
been reported for more than a decade but there is controversy regarding their
tissue activity and clinical significance. STUDY DESIGN, SIZE, DURATION: This
case-controlled research study was conducted with prospectively collected normal
peritoneal samples from 151 women with and 62 women without visible
endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Normal peritoneal biopsy
specimens from different pelvic sites of were collected during laparoscopy. A
histological search of all peritoneal biopsy specimens for the detection of
invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell
marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker).
Tissue expression of estrogen/progesterone receptors (ER/PR) and cell
proliferation marker, Ki-67, was performed by immunohistochemistry to identify
tissue activity. MAIN RESULTS AND THE ROLE OF CHANCE: Three different patterns of
OME were detected based on (I) the presence of typical gland/stroma, (II)
reactive hyperplastic change of endometrioid epithelial cells with surrounding
stroma and (III) single-layered epithelium-lined cystic lesions with surrounding
stroma. A higher tendency toward the occurrence of OME was found in women with
visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P
= 0.06, chi(2) test). The epithelial cells and/or stromal cells of OME lesions
were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR
expression was observed in all patterns of OME lesions. Ki-67 index was
significantly higher in pattern I/II OME lesions than in pattern III OME lesions
(P< 0.05 for each). LIMITATIONS, REASONS FOR CAUTION: Bias in the incidence rate
of OME lesions in this study cannot be ignored, because we could not analyze
biopsy specimens from the Pouch of Douglas of women with revised classification
of the American Society of Reproductive Medicine Stage III-IV endometriosis due
to the presence of adhesions in the pelvis. WIDER IMPLICATIONS OF THE FINDINGS:
We re-confirmed a decade long old concept of invisible (occult) endometriosis in
visually normal peritoneum of women with visible endometriosis. The existence of
a variable amount of tissue activity in these occult lesions may contribute to
the recurrence/occurrence of endometriosis or persistence/recurrence of pain
manifestation in women even after successful ablation or excision of visible
lesions by laparoscopy. STUDY FUNDING/COMPETING INTEREST(S): This work was
supported in part by Grants-in-aid for Scientific Research from the Japan Society
for the Promotion of Science. There is no conflict of interest related to this
study. TRIAL REGISTRATION NUMBER: Not applicable.
PMID- 24352889
TI - Ectopic pregnancy prediction in women with a pregnancy of unknown location: data
beyond 48 h are necessary.
AB - STUDY QUESTION: Are there improvements in the accuracy of prediction of ectopic
pregnancy (EP) in women with early symptomatic pregnancy using human chorionic
gonadotrophin (hCG) curves when clinicians consider visits beyond the first 48 h
after initial presentation? SUMMARY ANSWER: Two hCG values, measured 48 h (2
days) apart, are often not sufficient to accurately predict the outcome of a
woman with a pregnancy of unknown location (PUL), but adding a third visit on Day
4 or 7 significantly improved the prediction for 1 in 15 women. WHAT IS KNOWN
ALREADY: The use of serial hCG values is commonly used to aid in the prediction
of the final diagnosis in women with a PUL. Initial outcome predictions based on
two hCG values may often be incorrect. STUDY DESIGN, SIZE, DURATION: This
retrospective multicenter cohort study included 646 women with a PUL, recruited
over 2 years. Of these women, 146 were ultimately diagnosed with EP.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women presenting to the emergency room
with first trimester pain or bleeding, with a PUL, at least 2 hCG values and a
definitive final diagnosis from the University of Pennsylvania, University of
Miami and University of Southern California, were recruited from 2007 to 2009.
MAIN RESULTS AND THE ROLE OF CHANCE: Using currently recommended prediction
rules, adding a third hCG evaluation on Day 4 after initial presentation
significantly improved the accuracy of initial prediction from the first two
values (48 h apart, or Day 2) by 9.3% (P = 0.015). Adding a third value on Day 7
improved prediction significantly by 6.7% (P = 0.031), compared with prediction
based on first two values. The improvement in prediction by assessing four hCG
values (Days 0, 2, 4 and 7) compared with three values (Days 0, 2 and 4) was 1.3%
and not statistically significant. LIMITATIONS, REASONS FOR CAUTION: Missing data
imputation likely biased results toward the null; predicted outcomes may not
match those made by clinicians; and the study does not predict intrauterine
pregnancy and spontaneous miscarriage separately. WIDER IMPLICATIONS OF THE
FINDINGS: This study provides useful information for the prediction of outcomes
for women with a symptomatic first trimester pregnancy of unknown location, but
may not be generalizable to all pregnant women. STUDY FUNDING/COMPETING
INTEREST(S): Supported by NIH grant numbers R01-HD036455 to Dr Barnhart and Dr
Sammel, K24HD060687 to Dr Barnhart, and 5T32MH065218 to Ms. Zee. The authors have
no conflicts of interest to declare.
PMID- 24352891
TI - Transcription factor and bone marrow stromal cells in osseointegration of dental
implants.
AB - Titanium implants are widely used in dental clinics and orthopaedic surgery.
However, bone formation surrounding the implant is relatively slow after
inserting the implant. The current study assessed the effects of bone marrow
stromal cells (BMSCs) with forced expression of special AT-rich sequence-binding
protein 2 (SATB2) on the osseointegration of titanium implants. To determine
whether SATB2 overexpression in BMSCs can enhance the osseointegration of
implants, BMSCs were infected with the retrovirus encoding Satb2 (pBABE-Satb2)
and were locally applied to bone defects before implanting the titanium implants
in the mouse femur. Seven and twenty-one days after implantation, the femora were
isolated for immunohistochemical (IHC) staining, haematoxylin eosin (H&E)
staining, real-time quantitative reverse transcription polymerase chain reaction
(qRT-PCR), and micro-computed tomography (MUCT) analysis. IHC staining analysis
revealed that SATB2-overexpressing BMSCs were intensely distributed in the bone
tissue surrounding the implant. Histological analysis showed that SATB2
overexpressing BMSCs significantly enhanced new bone formation and bone-to
implant contact 3 weeks after implantation. Real-time qRT-PCR results showed that
the local delivery of SATB2-overexpressing BMSCs enhanced expression levels of
potent osteogenic transcription factors and bone matrix proteins in the
implantation sites. MUCT analysis demonstrated that SATB2-overexpressing BMSCs
significantly increased the density of the newly formed bone surrounding the
implant 3 weeks post-operatively. These results conclude that local delivery of
SATB2-overexpressing BMSCs significantly accelerates osseointegration of titanium
implants. These results provide support for future pharmacological and clinical
applications of SATB2, which accelerates bone regeneration around titanium
implants.
PMID- 24352892
TI - Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.
AB - Parkinson's disease is characterized by the pathological aggregation of Alpha
synuclein. The dual-hit hypothesis proposed by Braak implicates the enteric
nervous system as an initial site of alpha-synuclein aggregation with subsequent
spread to the central nervous system. Regional variations in the spatial pattern
or levels of alpha-synuclein along the enteric nervous system could have
implications for identifying sites of onset of this pathogenic cascade. We
performed immunohistochemical staining for alpha-synuclein on gastrointestinal
tissue from patients with no history of neurological disease using the
established LB509 antibody and a new clone, MJFR1, characterized for
immunohistochemistry here. We demonstrate that the vermiform appendix is
particularly enriched in alpha-synuclein-containing axonal varicosities,
concentrated in its mucosal plexus rather than the classical submucosal and
myenteric plexuses. Unexpectedly, intralysosomal accumulations of alpha-synuclein
were detected within mucosal macrophages of the appendix. The abundance and
accumulation of alpha-synuclein in the vermiform appendix implicate it as a
candidate anatomical locus for the initiation of enteric alpha-synuclein
aggregation and permits the generation of testable hypotheses for Parkinson's
disease pathogenesis.
PMID- 24352893
TI - Anterior trans-frontal endoscopic management of colloid cyst: an effective, safe,
and elegant way of treatment. Case series and technical note from a multicenter
prospective study.
AB - Different management options are available for the treatment of colloid cysts.
Goals of those procedures are to achieve a complete resection avoiding potential
long-term recurrence along with CSF pathways restoration with minimal morbidity
and mortality. The two main surgical options are endoscopic resection or direct
removal by either transfrontal or transcallosal approach. The efficacy of
endoscopic technique to achieve gross total colloid cyst excision has been well
documented. In the present study, authors describe a series of 29 patients who
underwent surgery by a variation of the standard worldwide implemented endoscopic
technique. Using a more anterior approach, it is easier to reach the roof of the
cyst, its possible adherences with the tela choroidea, plexus, and the internal
cerebral veins. The described approach has shown to be safe, quick, and very
effective with a total cyst removal rate of 86.2%.
PMID- 24352894
TI - Primary extranodal marginal zone B cell lymphoma of the uterus: a case study and
review of the literature.
PMID- 24352896
TI - The development of the bioartificial lung.
AB - INTRODUCTION OR BACKGROUND: The incidence of chronic lung disease is increasing
worldwide due to the spread of risk factors and ageing population. An important
advance in treatment would be the development of a bioartificial lung where the
blood-gas exchange surface is manufactured from a synthetic or natural scaffold
material that is seeded with the appropriate stem or progenitor cells to mimic
the functional tissue of the natural lung. SOURCES OF DATA: Articles relating to
bioartificial lungs were sourced through PubMed and ISI Web of Knowledge. AREAS
OF AGREEMENT: There is a consensus that advances in bioartificial lung
engineering will be beneficial to patients with chronic lung failure. Ultimate
success will require the concerted efforts of researchers drawn from a broad
range of disciplines, including clinicians, cell biologists, materials scientists
and engineers. AREAS OF CONTROVERSY: As a source of cells for use in
bioartificial lungs it is proposed to use human embryonic stem cells; however,
there are ethical and safety concerns regarding the use of these cells. GROWING
POINTS: There is a need to identify the optimum strategies for differentiating
progenitor cells into functional lung cells; a need to better understand cell
biomaterial/ECM interactions and a need to understand how to harness the body's
natural capacity to regenerate the lung. AREAS TIMELY FOR DEVELOPING RESEARCH:
Biomaterial technologies for recreating the natural lung ECM and architecture
need further development. Mathematical modelling techniques should be developed
for determining optimal scaffold seeding strategies and predicting gas exchange
performance.
PMID- 24352897
TI - How to improve your PubMed/MEDLINE searches: 2. display settings, complex search
queries and topic searching.
AB - The way that PubMed results are displayed can be changed using the Display
Settings drop-down menu in the result screen. There are three groups of options:
Format, Items per page and Sort by, which allow a good deal of control. The
results from several searches can be temporarily stored on the Clipboard. Records
of interest can be selected on the results page using check boxes and can then be
combined, for example to form a reference list. The Related Citations is a
valuable feature of PubMed that can provide a set of similar articles when you
have identified a record of interest among the results. You can easily search for
RCTs or reviews using the appropriate filters or field tags. If you are
interested in clinical articles, rather than basic science or health service
research, then the Clinical Queries tool on the PubMed home page can be used to
retrieve them.
PMID- 24352898
TI - Teledermatology in the diagnosis of melanoma.
AB - We conducted a retrospective chart review of US Veterans in the Pacific Northwest
area to compute melanoma incidence and Breslow depth at diagnosis. We compared
Veterans with access to teledermatology (TD) and those without (non-TD). We
identified pathology-confirmed primary melanomas in Veterans who had had at least
one encounter at a VA facility during a 3-year study period. The age-adjusted
melanoma incidence for all, TD and non-TD Veterans was 36, 15 and 57 per 100,000,
respectively. The mean Breslow depth was significantly greater in the TD group (P
= 0.03). Although a higher proportion of thin (Breslow depth <=1 mm) TD melanomas
were mitotically active, this difference was not significant. We also found that
180 (40%) of the non-TD (face-to-face) diagnosed melanomas were from Veterans
living in areas where TD was available. This suggests that the higher melanoma
incidence in the non-TD group was mainly due to under-utilization of TD services.
The study demonstrated that the TD service was not fully utilized in the VISN20
region, although the reasons for this are not clear. Where TD was utilized it
tended to diagnose more advanced melanomas with worse initial prognosis.
PMID- 24352899
TI - A meta-analysis of remote patient monitoring for chronic heart failure patients.
AB - We carried out a meta analysis of remote patient monitoring (RPM) for chronic
heart failure (CHF) patients. A literature search was used to identify randomised
controlled trials with more than 40 patients, published between February 2003 and
February 2013. The primary outcome (mortality) was analysed using a random effect
model. Thirteen studies were included (3337 patients). RPM resulted in a
significantly lower mortality (risk ratio 0.76; 95% confidence interval 0.62 to
0.93) compared to usual care. The test for heterogeneity showed that articles had
been extracted homogeneously (I(2)=0%, P=0.67). In order to determine which RPM
model was most effective, subgroup analyses were conducted by age, severity of
illness, measurement frequency, medication management and speed of intervention.
The group with rapid intervention had the lowest mortality (rapid group risk
ratio=0.59, non-rapid group risk ratio=0.88, P=0.05). The group with high
measurement frequency had lower mortality (high frequency group risk ratio=0.62,
low frequency group risk ratio=0.89, P=0.07). The group with medication
management had lower mortality (medication group risk ratio=0.65, non medication
group risk ratio=0.85, P=0.19). RPM is effective in chronic heart failure and
rapid intervention was the most important factor in the RPM model.
PMID- 24352900
TI - Robot-assisted home hazard assessment for fall prevention: a feasibility study.
AB - We examined the feasibility of using a remotely manoeuverable robot to make home
hazard assessments for fall prevention. We employed use-case simulations to
compare robot assessments with in-person assessments. We screened the homes of
nine elderly patients (aged 65 years or more) for fall risks using the HEROS
screening assessment. We also assessed the participants' perspectives of the
remotely-operated robot in a survey. The nine patients had a median Short Blessed
Test score of 8 (interquartile range, IQR 2-20) and a median Life-Space
Assessment score of 46 (IQR 27-75). Compared to the in-person assessment (mean =
4.2 hazards identified per participant), significantly more home hazards were
perceived in the robot video assessment (mean = 7.0). Only two checklist items
(adequate bedroom lighting and a clear path from bed to bathroom) had more than
60% agreement between in-person and robot video assessment. Participants were
enthusiastic about the robot and did not think it violated their privacy. The
study found little agreement between the in-person and robot video hazard
assessments. However, it identified several research questions about how to best
use remotely-operated robots.
PMID- 24352901
TI - Teleconsultation in vascular surgery: a 13 year single centre experience.
AB - The University Hospital of Zurich has provided an email-based medical
consultation service for the general public since 1999. We examined the enquiries
in a 13-year period to identify those related to vascular surgery (based on 22
ICD-10 codes specific for vascular surgery). There were 40,062 questions, of
which 643 (2%) were selected by ICD-10 codes. After exclusion of diagnoses not
relevant to vascular surgery, 139 questions remained, i.e. an average rate of
about one per month. The mean age of the users was 43 years (range 19-88). Most
users (61%) were women. The majority of users asked questions about their own
health problems (79%) with varicose veins and spider veins accounting for 63% of
all questions. Arterial diseases accounted for 30%. The patient's intention in
contacting the service was to obtain advice on treatment options (37%),
information about a diagnosis or symptoms (27%), or a second opinion (15%). The
online service responded with detailed information and advice (87%) and suggested
a referral to the family doctor or a specialist in 75%. Most patients (82%) rated
the service overall as good or very good. It appears likely that telemedicine and
in particular email teleconsultations will increase in vascular surgery in the
future.
PMID- 24352906
TI - Tumor heterogeneity revealed by KRAS, BRAF, and PIK3CA pyrosequencing: KRAS and
PIK3CA intratumor mutation profile differences and their therapeutic
implications.
AB - Current clinical problems in colorectal cancer (CRC) diagnostics and therapeutics
include the disease complexity, tumor heterogeneity, and resistance to targeted
therapeutics. In the present study, we examined 171 CRC adenocarcinomas from
Greek patients undergoing surgery for CRC to determine the frequency of KRAS,
BRAF, and PIK3CA point mutations from different areas of tumors in heterogeneous
specimens. Ninety two out of 171 (53.8%) patients were found to bear a KRAS
mutation in codons 12/13. Of the 126 mutations found, 57.9% (73/126) were c.38G>A
mutations (p.G13D) and 22.2% (28/126) were c.35G>T (p.G12V). Remarkably, RAS
mutations in both codons 12 and 13 were recorded in the same tumor by
pyrosequencing. Moreover, differences in KRAS mutations between tumor center and
periphery revealed tumor heterogeneity in 50.7% of the specimens. BRAF c.1799T>A
(V600E) mutations were moderately detected in 4/171 (2.3%) specimens, whereas
most PIK3CA mutations were revealed by pyrosequencing 6/171 (3.5%). Remarkable
tumor heterogeneity is revealed, where double mutations of KRAS in the same tumor
and different KRAS mutation status between tumor core and margin are detected
with high frequency. It is expected that these findings will have a major impact
in cancer diagnosis and personalized therapies.
PMID- 24352907
TI - Modeling health-related quality of life in people recovering from stroke.
AB - BACKGROUND: The Wilson-Cleary (W-C) model of health-related quality of life
(HRQL) has not been tested in stroke, and a better understanding of the
components of HRQL during recovery would lead to a more integrated and person
centered approach to health management and outcome optimization for this
vulnerable population. OBJECTIVE: To enhance our understanding for how QOL
emerges from the sequelae of stroke during the recovery period, the aim was to
empirically test a biopsychosocial conceptual model of HRQL for people recovering
from stroke. METHODS: We present a multi-site longitudinal study of an inception
cohort of 678 persons recruited at stroke onset and studied at key intervals over
the first post-stroke year. As the most pronounced recovery after stroke occurs
in the first 3 months, this time frame was chosen as the focus of this analysis.
The measures for this study were chosen for their relevance to key constructs of
stroke impact and for their optimal psychometric properties. Multiple measures
for each of the W-C rubrics were available from instruments such as the Stroke
Impact Scale, RAND-36, HUI, and EQ-5D, among others. A structural equation model
(SEM) was fit using MPlus. To minimize potential bias arising from the missing
data, multiple imputation was performed on the longitudinal data using SAS proc
MI. RESULTS: Of the 678 subjects who entered the cohort, 618 were interviewed at
1 month post-stroke and 533 at 3 months (486 and 454 had data at 6 and 12 months,
respectively). A 3-month model with paths from biological factors to symptoms and
symptoms to function fits well (CFI:0.966, RMSEA:0.044), though one model with
paths from function to health perception did not (CFI:0.934, RMSEA:0.058).
Allowing additional paths across non-adjacent rubrics improved fit considerably
(CFI:0.962, RMSEA:0.044). A final model included emotional well-being under the
symptom rubric (CFI:0.955, RMSEA:0.047). Including social support as an
environmental factor had little impact on the model. Total variance in health
perception explained was 76.3 %. CONCLUSION: These results emphasize that to
optimize overall HRQL during the crucial first 3 months of recovery,
interventions need to continue to focus on comorbid health conditions and on
reducing stroke impairments. A function-only focus too soon in the recovery
process may not produce the desired impact to optimize HRQL.
PMID- 24352909
TI - Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor
combination with activity against multidrug-resistant gram-negative bacilli.
AB - Ceftolozane is a novel cephalosporin currently being developed with the beta
lactamase inhibitor tazobactam for the treatment of complicated urinary tract
infections (cUTIs), complicated intra-abdominal infections (cIAIs), and
ventilator-associated bacterial pneumonia (VABP). The chemical structure of
ceftolozane is similar to that of ceftazidime, with the exception of a modified
side-chain at the 3-position of the cephem nucleus, which confers potent
antipseudomonal activity. As a beta-lactam, its mechanism of action is the
inhibition of penicillin-binding proteins (PBPs). Ceftolozane displays increased
activity against Gram-negative bacilli, including those that harbor classical
beta-lactamases (e.g., TEM-1 and SHV-1), but, similar to other oxyimino
cephalosporins such as ceftazidime and ceftriaxone, it is compromised by extended
spectrum beta-lactamases (ESBLs) and carbapenemases. The addition of tazobactam
extends the activity of ceftolozane to include most ESBL producers as well as
some anaerobic species. Ceftolozane is distinguished from other cephalosporins by
its potent activity versus Pseudomonas aeruginosa, including various drug
resistant phenotypes such as carbapenem, piperacillin/tazobactam, and ceftazidime
resistant isolates, as well as those strains that are multidrug-resistant (MDR).
Its antipseudomonal activity is attributed to its ability to evade the multitude
of resistance mechanisms employed by P. aeruginosa, including efflux pumps,
reduced uptake through porins and modification of PBPs. Ceftolozane demonstrates
linear pharmacokinetics unaffected by the coadministration of tazobactam;
specifically, it follows a two-compartmental model with linear elimination.
Following single doses, ranging from 250 to 2,000 mg, over a 1-h intravenous
infusion, ceftolozane displays a mean plasma half-life of 2.3 h (range 1.9-2.6
h), a steady-state volume of distribution that ranges from 13.1 to 17.6 L, and a
mean clearance of 102.4 mL/min. It demonstrates low plasma protein binding (20
%), is primarily eliminated via urinary excretion (>=92 %), and may require dose
adjustments in patients with a creatinine clearance <50 mL/min. Time-kill
experiments and animal infection models have demonstrated that the
pharmacokinetic-pharmacodynamic index that is best correlated with ceftolozane's
in vivo efficacy is the percentage of time in which free plasma drug
concentrations exceed the minimum inhibitory concentration of a given pathogen
(%fT >MIC), as expected of beta-lactams. Two phase II clinical trials have been
conducted to evaluate ceftolozane +/- tazobactam in the settings of cUTIs and
cIAIs. One trial compared ceftolozane 1,000 mg every 8 h (q8h) versus ceftazidime
1,000 mg q8h in the treatment of cUTI, including pyelonephritis, and demonstrated
similar microbiologic and clinical outcomes, as well as a similar incidence of
adverse effects after 7-10 days of treatment, respectively. A second trial has
been conducted comparing ceftolozane/tazobactam 1,000/500 mg and metronidazole
500 mg q8h versus meropenem 1,000 mg q8h in the treatment of cIAI. A number of
phase I and phase II studies have reported ceftolozane to possess a good safety
and tolerability profile, one that is consistent with that of other
cephalosporins. In conclusion, ceftolozane is a new cephalosporin with activity
versus MDR organisms including P. aeruginosa. Tazobactam allows the broadening of
the spectrum of ceftolozane versus beta-lactamase-producing Gram-negative bacilli
including ESBLs. Potential roles for ceftolozane/tazobactam include empiric
therapy where infection by a resistant Gram-negative organism (e.g., ESBL) is
suspected, or as part of combination therapy (e.g., with metronidazole) where a
polymicrobial infection is suspected. In addition, ceftolozane/tazobactam may
represent alternative therapy to the third-generation cephalosporins after
treatment failure or for documented infections due to Gram-negative bacilli
producing ESBLs. Finally, the increased activity of ceftolozane/tazobactam versus
P. aeruginosa, including MDR strains, may lead to the treatment of suspected and
documented P. aeruginosa infections with this agent. Currently,
ceftolozane/tazobactam is being evaluated in three phase III trials for the
treatment of cUTI, cIAI, and VABP.
PMID- 24352910
TI - Hierarchical growth of fluorescent dye aggregates in water by fusion of segmented
nanostructures.
AB - Dye aggregates are becoming increasingly attractive for diverse applications, in
particular as organic electronic and sensor materials. However, the growth
processes of such aggregates from molecular to small assemblies up to
nanostructures is still not properly understood, limiting the design of
materials' functional properties. Here we elucidate the supramolecular growth
process for an outstanding class of functional dyes, perylene bisimides (PBIs),
by transmission electron microscopy (TEM), cryogenic scanning electron microscopy
(cryo-SEM), and atomic force microscopy (AFM). Our studies reveal a sequential
growth of amphiphilic PBI dyes from nanorods into nanoribbons in water by fusion
and fission processes. More intriguingly, the fluorescence observed for higher
hierarchical order nanoribbons was enhanced relative to that of nanorods. Our
results provide insight into the relationship between molecular, morphological,
and functional properties of self-assembled organic materials.
PMID- 24352911
TI - Genetic diversity of four populations of Qualea grandiflora Mart. in fragments of
the Brazilian Cerrado.
AB - We analyzed the genetic structure and diversity of Qualea grandiflora Mart., the
most abundant woody species in the Brazilian Cerrado. Eight microsatellite loci
were used to analyze samples from four populations subjected to different types
of anthropic pressure, distributed throughout the state of Sao Paulo in the
regions of Assis, Brotas, Itirapina and Pedregulho. Results indicated a mean
number of 12 alleles per locus, but only six effective alleles. Alleles private
to particular populations and rare alleles were also detected. An excess of
homozygotes and moderate levels of inbreeding were observed. No clones were
identified. All populations departed from Hardy-Weinberg equilibrium (p < 0.05).
Spatial structure was observed in the distribution of specimens in distance
classes ranging from 30 to 40 km and three genetic clusters were identified, with
genotypes in the Pedregulho population differing from the others by up to 90 %.
The influence of the Wahlund effect on the studied populations lies between 8.5
and 53.3 %. Estimates of effective population size were low (<10), and the
minimum viable area for conservation in the short-, medium- and long-term was
estimated to be between 4 and 184 ha. Gene flow was high enough to counter the
effects of genetic drift. The genetic diversity and divergence between the
studied populations indicated that the Pedregulho population should be considered
an Evolutionary Significant Unit and a Management Unit.
PMID- 24352913
TI - Characterization of core clinical phenotypes associated with recurrent proximal
15q25.2 microdeletions.
AB - A recurrent proximal microdeletion at 15q25.2 with an approximate 1.5 megabase
smallest region of overlap has recently been reported in seven patients and is
proposed to be associated with congenital diaphragmatic hernia (CDH), mild to
moderate cognitive deficit, and/or features consistent with Diamond-Blackfan
anemia. We report on four further patients and define the core phenotypic
features of individuals with this microdeletion to include mild to moderate
developmental delay or intellectual disability, postnatal short stature, anemia,
and cryptorchidism in males. CDH and structural organ malformations appear to be
less frequent associations, as is venous thrombosis. There is no consistent
facial dysmorphism. Features novel to our patient group include dextrocardia,
obstructive sleep apnea, and cleft lip.
PMID- 24352912
TI - Complexities in the relationship between infection and autoimmunity.
AB - The possible role of infections in driving autoimmune disease (AD) has long been
debated. Many theories have emerged including release of hidden antigens, epitope
spread, anti-idiotypes, molecular mimicry, the adjuvant effect, antigenic
complementarity, or simply that AD could be a direct consequence of activation or
subversion of the immune response by microbes. A number of issues are not
adequately addressed by current theories, including why animal models of AD
require adjuvants containing microbial peptides in addition to self tissue to
induce disease, and why ADs occur more often in one sex than the other. Reviews
published in the past 3 years have focused on the role of the innate immune
response in driving AD and the possible role of persistent infections in altering
immune responses. Overall, recent evidence suggests that microbes activating
specific innate immune responses are critical, while antigenic cross-reactivity
may perpetuate immune responses leading to chronic autoinflammatory disease.
PMID- 24352914
TI - Anxiety, attention problems, hyperactivity, and the Aberrant Behavior Checklist
in fragile X syndrome.
AB - Behavior problems are a common challenge for individuals with fragile X syndrome
(FXS) and constitute the primary clinical outcome domain in trials testing new
FXS medications. However, little is known about the relationship between
caregiver-reported behavior problems and co-occurring conditions such as anxiety
and attention problems. In this study, 350 caregivers, each with at least one son
or daughter with full-mutation FXS, rated one of their children with FXS using
the Aberrant Behavior Checklist-Community Version (ABC-C); the Anxiety subscale
of the Anxiety, Depression, and Mood Scale; and the Attention/Hyperactivity Items
from the Symptom Inventories. In addition to examining family consequences of
these behaviors, this study also sought to replicate psychometric findings for
the ABC-C in FXS, to provide greater confidence for its use in clinical trials
with this population. Psychometric properties and baseline ratings of problem
behavior were consistent with other recent studies, further establishing the
profile of problem behavior in FXS. Cross-sectional analyses suggest that
selected dimensions of problem behavior, anxiety, and hyperactivity are age
related; thus, age should serve as an important control in any studies of problem
behavior in FXS. Measures of anxiety, attention, and hyperactivity were highly
associated with behavior problems, suggesting that these factors at least
coincide with problem behavior. However, these problems generally did not add
substantially to variance in caregiver burden predicted by elevated behavior
problems. The results provide further evidence of the incidence of problem
behaviors and co-occurring conditions in FXS and the impact of these behaviors on
the family.
PMID- 24352915
TI - Pathogenesis of congenital diaphragmatic hernia: additional clues regarding the
involvement of the endothelin system.
AB - Congenital diaphragmatic hernia (CDH) has an incidence of around 1/3,000 births.
The pathogenesis of this developmental anomaly remains largely unknown and the
description of small chromosomal imbalances in cases of CDH is of major interest
for the identification of candidate genes. We report on a tandem 4q31.23
triplication encompassing the EDNRA gene identified by array-CGH in a male
presenting an isolated left postero-lateral CDH. This copy number variation was
inherited from the asymptomatic father, carrier of a size-identical duplication.
We demonstrate that EDNRA mRNA is over-expressed in the proband in blood tissue.
Consistent with the expression of EDNRA in the developing diaphragm and the
observation that the endothelin system is up-regulated in human and animal models
of CDH, we conclude that the EDNRA triplication may be the cause of CDH in our
patient.
PMID- 24352916
TI - Aortic aneurysm and craniosynostosis in a family with Cantu syndrome.
AB - Cantu syndrome is an autosomal dominant overgrowth syndrome associated with
facial dysmorphism, congenital hypertrichosis, and cardiomegaly. Some affected
individuals show bone undermodeling of variable severity. Recent investigations
revealed that the disorder is caused by a mutation in ABCC9, encoding a
regulatory SUR2 subunit of an ATP-sensitive potassium channel mainly expressed in
cardiac and skeletal muscle as well as vascular smooth muscle. We report here on
a Japanese family with this syndrome. An affected boy and his father had a novel
missense mutation in ABCC9. Each patient had a coarse face and hypertrichosis.
However, cardiomegaly was seen only in the boy, and macrosomia only in the
father. Skeletal changes were not evident in either patient. Craniosynostosis in
the boy and the development of aortic aneurysm in the father are previously
undescribed associations with Cantu syndrome.
PMID- 24352917
TI - Suppression of severe achondroplasia with developmental delay and acanthosis
nigricans by the p.Thr651Pro mutation.
AB - Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN)
is an extremely rare severe skeletal dysplasia characterized by significant
developmental delay, brain structural abnormalities, hearing loss, and acanthosis
nigricans. The disorder is the result of a single missense mutation at codon 650
(p.Lys650Met) in the fibroblast growth factor receptor 3 gene (FGFR3). We
describe a child who initially presented with a mild achondroplasia or
hypochondroplasia like phenotype. Molecular analysis of the FGFR3 gene showed the
common SADDAN mutation and a second novel mutation at codon 651 (p.Thr651Pro).
Both mutations were shown to occur on the same allele (cis) and de novo.
Transient transfection studies with FGFR3 double mutant constructs show that the
p.Thr651Pro mutation causes a dramatic decrease in constitutive receptor kinase
activity than that observed by the p.Lys650Met mutation. Our data suggest that
the molecular effect by the p.Thr651Pro is to elicit a conformational change that
decreases the FGFR3 tyrosine kinase activity, which is constitutively activated
by the SADDAN mutation. Due to the inheritance of both a gain-of-function and a
loss-of-function mutation, we conclude that a reduction of constitutive
activation caused the milder skeletal phenotype. Although the occurrence of
double mutations are expected to be rare, the presence of other FGFR3 modifiers
may be responsible for some of the clinically discrepant skeletal dysplasia
cases.
PMID- 24352918
TI - Exome sequencing identifies a novel EP300 frame shift mutation in a patient with
features that overlap Cornelia de Lange syndrome.
AB - Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are
genetically heterogeneous multiple anomalies syndromes, each having a distinctive
facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five
(NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A
diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically
identified cases, suggesting that additional causative genes exist for both
conditions. In addition, although EP300 and CREBBP encode homologous proteins and
perform similar functions, only eight EP300 positive RTS patients have been
reported, suggesting that patients with EP300 mutations might be escaping
clinical recognition. We report on a child with multiple congenital abnormalities
and intellectual disability whose facial features and complex phenotype resemble
CdLS. However, no mutations in CdLS-related genes were identified. Rather, a
novel EP300 mutation was found on whole exome sequencing. Possible links between
EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8
are involved in the regulation of TP53 transcriptional activity. In addition,
p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3,
have been found at enhancer regions in different cell types. It is therefore
possible that EP300 and CdLS-related genes are involved in additional shared
pathways, producing overlapping phenotypes. As whole exome sequencing becomes
more widely utilized, the diverse phenotypes associated with EP300 mutations
should be better understood. In the meantime, testing for EP300 mutations in
those with features of CdLS may be warranted.
PMID- 24352919
TI - Whole-exome sequencing emerges as clinical diagnostic tool: testing method proves
useful for diagnosing wide range of genetic disorders.
PMID- 24352920
TI - Who should control genomic data?: Researchers advocate putting patients in charge
of their own results.
PMID- 24352923
TI - Survey of patient satisfaction after Doppler-guided transanal hemorrhoidal
dearterialization performed in ambulatory settings.
AB - BACKGROUND: Transanal hemorrhoidal dearterialization (THD) is a recently
developed procedure to minimize postoperative pain from hemorrhoidectomy. This
technique utilizes Doppler signals to aid ligation of hemorrhoidal arteries
followed by mucopexy of redundant mucosa if needed. The aim of the present study
was to assess patient satisfaction after THD. METHODS: This is a retrospective
cohort study of patients who underwent THD at three different sites from April
2007 through October 2010. All procedures were performed in ambulatory settings
according to protocol. Telephone surveys were conducted after a minimum of 1
month follow-up to assess patients' satisfaction on a scale of 1-10. Patients
were asked whether the procedure had alleviated their symptoms. Patients were
asked to recall duration of pain and time from surgery to return to work.
RESULTS: Between April 2007 and October 2010, 216 patients with grade III-IV
hemorrhoids underwent THD. There were 165 males and 61 females. Average age was
52.2 +/- 14.2 years. All patients were discharged the same day after meeting
ambulatory surgery center discharge criteria. Postoperative difficulty urinating
occurred in 37 (17 %) patients, and six of them required temporary urinary
catheterization. Transitory postoperative bleeding was reported by 38 (18 %)
patients. Transitory incontinence to stool and flatus occurred in 18 (9 %) and 16
patients (8 %), respectively. Pelvic muscle spasms occurred in 21 (10 %)
patients. Median follow-up was 23 months (range 1-42 months) with 143 (66 %)
having at least 9 months between procedure and interview. Mean patient
satisfaction was 8.5 +/- 0.7 (on a scale of 1-10 with 10 being the best), and
91.5 % of patients felt the procedure had "helped" them. Average number of days
with discomfort was 6.7 +/- 2.1. Patients returned to work after an average of
10.3 +/- 3.2 days. Our study is limited by lack of long-term follow-up and by
retrospective complication assessment. CONCLUSIONS: Patient satisfaction with THD
performed in ambulatory settings is high. Our data support performance of this
procedure in an ambulatory setting.
PMID- 24352924
TI - Is portable ultrasonography accurate in the evaluation of Schanz pin placement
during extremity fracture fixation in austere environments?
AB - OBJECTIVE: The purpose of this study was to investigate the efficacy of
ultrasonography to confirm Schanz pin placement in a cadaveric model, and the
interobserver repeatability of the ultrasound methodology. DESIGN: This
investigation is a repeated measures cadaveric study with multiple examiners.
PARTICIPANTS: Cadaveric preparation and observations were done by an orthopaedic
traumatologist and resident, and two general surgery traumatologists.
INTERVENTIONS: A total of 16 Schanz pins were equally placed in bilateral femora
and tibiae. Four examiners took measurements of pin protrusion beyond the distal
cortices using first ultrasonography and then by direct measurement after gross
dissection. MAIN OUTCOME MEASURE(S): Distal Schanz pin protrusion length
measurements from both ultrasonography and direct measurement post dissection.
RESULTS: Schanz pin protrusion measurements are underestimated by ultrasonography
(p < 0.01) by an average of 10 percent over the range of 5 to 18 mm, and they
display a proportional bias that increases the under reporting as the magnitude
of pin protrusion increases. Ultrasound data demonstrate good linear correlation
and closely represent actual protrusion values in the 5 to 12 mm range.
Interobserver repeatability analysis demonstrated that all examiners were not
statistically different in their measurements despite minimal familiarity with
the ultrasound methodology (p > 0.8). CONCLUSIONS: Despite the statistical
imparity of pin protrusion measurement via ultrasound compared to that of gross
dissection, a consideration of the clinical relevance of ultrasound measurement
bias during an austere operating theatre leads to the conclusion that
ultrasonography is an adequate methodology for Schanz pin protrusion measurement.
PMID- 24352925
TI - Gleaning data from disaster: a hospital-based data mining method to study all
hazard triage after a chemical disaster.
AB - OBJECTIVE: To describe the methods of evaluating currently available triage
models for their efficacy in appropriately triaging the surge of patients after
an all-hazards disaster. DESIGN: A method was developed for evaluating currently
available triage models using extracted data from medical records of the victims
from the Graniteville chlorine disaster. SETTING: On January 6, 2005, a freight
train carrying three tanker cars of liquid chlorine was inadvertently switched
onto an industrial spur in central Graniteville, SC. The train then crashed into
a parked locomotive and derailed. This caused one of the chlorine tankers to
rupture and immediately release ~60 tons of chlorine. Chlorine gas infiltrated
the town with a population of 7,000. PARTICIPANTS: This research focuses on the
victims who received emergency care in South Carolina. RESULTS: With our data
mapping and decision tree logic, the authors were successful in using the
available extracted clinical data to estimate triage categories for use in our
study. CONCLUSIONS: The methodology outlined in this article shows the potential
use of well-designed secondary analysis methods to improve mass casualty
research. The steps are reliable and repeatable and can easily be extended or
applied to other disaster datasets.
PMID- 24352927
TI - Disaster-related fatalities among US citizens traveling abroad.
AB - OBJECTIVE: To describe the locations and risk of death associated with natural
disaster fatalities for US citizens traveling abroad. DESIGN, SETTING, AND
PARTICIPANTS: A retrospective database review of US citizen disaster deaths
occurring worldwide. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Information on
fatalities due to disasters was abstracted from the US Department of State Web
site reporting deaths of US citizens abroad by non-natural causes from October
2002 through June 2012. The main outcome measures were the frequency of disaster
deaths and countries where disasters occurred. Descriptive statistics and rates
were used to evaluate the study data. RESULTS: There were 7,963 total non-natural
deaths of US citizens traveling abroad during the study period. Of these, 163
(2.0 percent) were disaster-related deaths, involving 19 disaster events in 15
countries. Only two disaster-related events resulted in more than two deaths of
US travelers-the 2010 earthquake in Haiti causing 121 fatalities (74.2 percent of
disaster deaths), and the 2004 tsunami in Thailand causing 22 fatalities (13.5
percent of disaster deaths). The approximate annual mean death rate for US
citizen travelers as a result of disaster events is 0.27 deaths/1 million
travelers, compared with 1.4 deaths/1 million residents due to disaster annually
within the United States. CONCLUSIONS: The risk of disaster-related fatality is
low for US citizens traveling abroad. Although disaster-related death among
travelers is unpredictable, during a period of almost 10 years, there was only
one reported death due to disaster in the five countries most frequently visited
by US travelers. Further investigation may identify population-, seasonal-,
country-, or location-specific risks from which prevention strategies can be
developed.
PMID- 24352926
TI - Risk factors for mortality in landslide- and flood-affected populations in
Uganda.
AB - OBJECTIVE: Assess mortality risk factors including age, sex, and disaster type,
in the March 2010 floods and landslides in Eastern Uganda and to compare time
period, cause, location, and receipt of medical care among landslide and flood
fatalities. DESIGN: A stratified cluster survey was conducted of 802 affected
households in community and camp locations. SETTING: Flood and landslide affected
populations in the East Uganda the districts of Baduda and Butaleja. RESPONDENTS:
Adult household members in 802 households were surveyed regarding household
member deaths in the floods and landslides areas. MAIN OUTCOME MEASURES: The
primary outcome measure was the odds of death associated with age, sex, and
disaster type (flood or landslide). The secondary outcome measure was the odds of
event (landslide or flood) among fatalities associated with sex, age, time period
of death, and cause of death. RESULTS: The odds of death were significantly
higher in landslide affected populations than in flood affected populations (OR
3.06, 95% CI 2.20-4.25, p < 0.001). Time period of death (p = 0.016), type of
death (p < 0.001), death after seeking medical care (p = 0.033), month of death
(p < 0.001), and cause of death (p < 0.001) were significantly associated with
increased odds of death due to landslides as compared to floods. CONCLUSIONS:
More deaths occurred due to landslides than floods, and landslide deaths were
more immediate, with a majority occurring on the day of the event. Females and
younger age groups faced a greater risk of death from the landslide than the
flood.
PMID- 24352928
TI - Italian medical students and disaster medicine: awareness and formative needs.
AB - OBJECTIVE: Over the last century, the number of disasters has increased. Many
governments and scientific institutions agree that disaster medicine education
should be included in the standard medical curriculum. Italian medical students'
perceptions of mass casualty incidents and disasters and whether-and if so to
what extent-such topics are part of their academic program were investigated.
DESIGN, SETTING, AND PARTICIPANTS: A Web-based survey was disseminated to all
students registered with the national medical students' association (Segretariato
Italiano Studenti Medicina), a member of the International Federation of Medical
Students' Associations. The survey consisted of 14 questions divided into four
sections. RESULTS: Six hundred thirty-nine medical students completed the survey;
38.7 percent had never heard about disaster medicine; 90.9 percent had never
attended elective academic courses on disaster medicine; 87.6 percent had never
attended non-academic courses on disaster medicine; 91.4 percent would welcome
the introduction of a course on disaster medicine in their core curriculum; and
94.1 percent considered a knowledge of disaster medicine important for their
future career. CONCLUSIONS: Most of the students surveyed had never attended
courses on disaster medicine during their medical school program. However,
respondents would like to increase their knowledge in this area and would welcome
the introduction of specific courses into the standard medical curriculum.
PMID- 24352930
TI - An academic medical center's response to widespread computer failure.
AB - As hospitals incorporate information technology (IT), their operations become
increasingly vulnerable to technological breakdowns and attacks. Proper emergency
management and business continuity planning require an approach to identify,
mitigate, and work through IT downtime. Hospitals can prepare for these disasters
by reviewing case studies. This case study details the disruption of computer
operations at Mount Sinai Medical Center (MSMC), an urban academic teaching
hospital. The events, and MSMC's response, are narrated and the impact on
hospital operations is analyzed. MSMC's disaster management strategy prevented
computer failure from compromising patient care, although walkouts and time-to
disposition in the emergency department (ED) notably increased. This incident
highlights the importance of disaster preparedness and mitigation. It also
demonstrates the value of using operational data to evaluate hospital responses
to disasters. Quantifying normal hospital functions, just as with a patient's
vital signs, may help quantitatively evaluate and improve disaster management and
business continuity planning.
PMID- 24352929
TI - Evaluation of regional hospitals' use of children in disaster drills.
AB - OBJECTIVE: Describe the prevalence of pediatric casualties in disaster drills by
community hospitals and determine if there is an association between the use of
pediatric casualties in disaster drills and the proximity of a community hospital
to a tertiary children's hospital. DESIGN: Survey, descriptive study. SETTING:
Tertiary children's hospital and surrounding community hospitals. PARTICIPANTS:
Hospital emergency management personnel for 30 general community hospitals in the
greater Cincinnati, Ohio region. INTERVENTIONS: None MAIN OUTCOME MEASURE(S): The
utilization of pediatric casualties in community hospital disaster drills and its
relationship to the distance of those hospitals from a tertiary children's
hospital. RESULTS: Sixteen hospitals reported a total of 57 disaster drills
representing 1,309 casualties. The overwhelming majority (82 percent
[1,077/1,309]) of simulated patients from all locations were 16 years of age or
older. Those hospitals closest to the children's hospital reported the lowest
percentage of pediatric patients (10 percent [35/357]) used in their drills. The
hospitals furthest from the children's hospital reported the highest percentage
of pediatric patients (32 percent [71/219]) used during disaster drills.
CONCLUSIONS: The majority of community hospitals do not incorporate children into
their disaster drills, and the closer a community hospital is to a tertiary
children's hospital, the less likely it is to include children in its drills.
Focused effort and additional resources should be directed toward preparing
community hospitals to care for children in the event of a disaster.
PMID- 24352931
TI - Internal radiation exposure of Ground Self-Defense Force members involved in the
management of the Fukushima Nuclear Power Plant disaster.
AB - When the Great East Japan Earthquake occurred on March 11, 2011, the Ground Self
Defense Force (GSDF) was dispatched nationally to Northeast area in Japan. The
highly trained GSDF members were simultaneously assigned to various missions for
the Fukushima Nuclear Power Plants disaster. The missions of GSDF terminated on
August 31, 2011. Special medical examinations were conducted for the members as
they returned to each military unit. GSDF members who were assigned to the
nuclear power plant were at risk of radiation exposure; therefore, pocket
dosimeters were used to assess external radiation exposure. A few months after
the mission was terminated, measurements of internal radiation exposure were
performed. This is the first report of the internal exposure of GSDF members who
worked in the restricted radiation contamination area. Here, we report the
amounts of internal and external exposure of and the equipment used by the GSDF
members.
PMID- 24352939
TI - Prohibition on assisting a suicide is interference with rights of severely
disabled people, UK Supreme Court is told.
PMID- 24352938
TI - Adoptive T-cell therapy for hematological malignancies using T cells gene
modified to express tumor antigen-specific receptors.
AB - The functional properties of the adoptive immune response mediated by effector T
lymphocytes are decisively regulated by their T-cell receptors (TCRs). Transfer
of genes encoding target antigen-specific receptors enables polyclonal T cells to
redirect toward cancer cells and virally infected cells expressing those defined
antigens. Using this technology, a large population of redirected T cells
displaying uniform therapeutic properties has been produced, powerfully advancing
their clinical application as "cellular drugs" for adoptive immunotherapy against
cancer. Clinically, anticancer adoptive immunotherapy using these genetically
engineered T cells has an impressive and proven track record. Notable examples
include the dramatic benefit of chimeric antigen receptor gene-modified T cells
redirected towards B-cell lineage antigen CD19 in patients with chronic
lymphocytic leukemia, and the impressive outcomes in the use of TCR gene-modified
T cells redirected towards NY-ESO-1, a representative cancer-testis antigen, in
patients with advanced melanoma and synovial cell sarcoma. In this review, we
briefly overview the current status of this treatment option in the context of
hematological malignancy, and discuss a number of challenges that still pose an
obstacle to the full effectiveness of this strategy.
PMID- 24352940
TI - Polarization distance: a framework for modelling object detection by polarization
vision systems.
AB - The discrimination of polarized light is widespread in the natural world. Its use
for specific, large-field tasks, such as navigation and the detection of water
bodies, has been well documented. Some species of cephalopod and crustacean have
polarization receptors distributed across the whole visual field and are thought
to use polarized light cues for object detection. Both object-based polarization
vision systems and large field detectors rely, at least initially, on an
orthogonal, two-channel receptor organization. This may increase to three
directional analysis at subsequent interneuronal levels. In object-based and some
of the large-field tasks, the dominant e-vector detection axes are often aligned
(through eye, head and body stabilization mechanisms) horizontally and vertically
relative to the outside world. We develop Bernard and Wehner's 1977 model of
polarization receptor dynamics to apply it to the detection and discrimination of
polarized objects against differently polarized backgrounds. We propose a measure
of 'polarization distance' (roughly analogous to 'colour distance') for
estimating the discriminability of objects in polarized light, and conclude that
horizontal/vertical arrays are optimally designed for detecting differences in
the degree, and not the e-vector axis, of polarized light under natural
conditions.
PMID- 24352941
TI - Vergence eye movements are not essential for stereoscopic depth.
AB - The brain receives disparate retinal input owing to the separation of the eyes,
yet we usually perceive a single fused world. This is because of complex
interactions between sensory and oculomotor processes that quickly act to reduce
excessive retinal disparity. This implies a strong link between depth perception
and fusion, but it is well established that stereoscopic depth percepts are also
obtained from stimuli that produce double images. Surprisingly, the nature of
depth percepts from such diplopic stimuli remains poorly understood.
Specifically, despite long-standing debate it is unclear whether depth under
diplopia is owing to the retinal disparity (directly), or whether the brain
interprets signals from fusional vergence responses to large disparities
(indirectly). Here, we addressed this question using stereoscopic afterimages,
for which fusional vergence cannot provide retinal feedback about depth. We
showed that observers could reliably recover depth sign and magnitude from
diplopic afterimages. In addition, measuring vergence responses to large
disparity stimuli revealed that that the sign and magnitude of vergence responses
are not systematically related to the target disparity, thus ruling out an
indirect explanation of our results. Taken together, our research provides the
first conclusive evidence that stereopsis is a direct process, even for diplopic
targets.
PMID- 24352942
TI - Correlates of depression in bipolar disorder.
AB - We analyse time series from 100 patients with bipolar disorder for correlates of
depression symptoms. As the sampling interval is non-uniform, we quantify the
extent of missing and irregular data using new measures of compliance and
continuity. We find that uniformity of response is negatively correlated with the
standard deviation of sleep ratings (rho = -0.26, p = 0.01). To investigate the
correlation structure of the time series themselves, we apply the Edelson-Krolik
method for correlation estimation. We examine the correlation between depression
symptoms for a subset of patients and find that self-reported measures of sleep
and appetite/weight show a lower average correlation than other symptoms. Using
surrogate time series as a reference dataset, we find no evidence that depression
is correlated between patients, though we note a possible loss of information
from sparse sampling.
PMID- 24352943
TI - Adaptive foraging behaviour of individual pollinators and the coexistence of co
flowering plants.
AB - Although pollinators can play a central role in determining the structure and
stability of plant communities, little is known about how their adaptive foraging
behaviours at the individual level, e.g. flower constancy, structure these
interactions. Here, we construct a mathematical model that integrates individual
adaptive foraging behaviour and population dynamics of a community consisting of
two plant species and a pollinator species. We find that adaptive foraging at the
individual level, as a complementary mechanism to adaptive foraging at the
species level, can further enhance the coexistence of plant species through niche
partitioning between conspecific pollinators. The stabilizing effect is stronger
than that of unbiased generalists when there is also strong competition between
plant species over other resources, but less so than that of multiple specialist
species. This suggests that adaptive foraging in mutualistic interactions can
have a very different impact on the plant community structure from that in
predator-prey interactions. In addition, the adaptive behaviour of individual
pollinators may cause a sharp regime shift for invading plant species. These
results indicate the importance of integrating individual adaptive behaviour and
population dynamics for the conservation of native plant communities.
PMID- 24352944
TI - Energetics of the acrobatic courtship in male golden-collared manakins (Manacus
vitellinus).
AB - In lek mating systems, females choose mates through indicators of quality, which
males may exhibit by their performance of courtship displays. In temperate
regions, displaying seasons are brief (one to two months), whereas in the tropics
courtship seasons may be prolonged. Moreover, in temperate-breeding animals
lekking behaviour can be energetically demanding, but little is known about the
energy costs of lekking in tropical animals. Daily, over the course of a nearly
seven-month-long breeding season, male golden-collared manakins (Manacus
vitellinus) of Panamanian rainforests perform acrobatic courtship displays that
markedly elevate heart rates, suggesting that they require high energy
investment. Typically, animals of tropical lowland forests (such as manakins)
exhibit a 'slow pace of life' metabolic strategy. We investigated whether male
manakin courtship is indeed metabolically costly or whether the birds retain a
low daily energy expenditure (DEE), as seen in other tropical species. To assess
these questions, we calibrated manakin heart rate against metabolic rate,
examined daily lek activity and, using telemetry, obtained heart rates of
individual wild, lekking male manakins. Although metabolic rates peak during
courtship displays, we found that males actually invest minimal time (only
approx. 5 min d(-1)) performing displays. As a consequence, the DEE of
approximately 39 kJ d(-1) for male manakins is comparable to other lowland
tropical species. The short, intense bursts of courtship by these birds make up
only approximately 1.2% of their total DEE. Presumably, this cost is negligible,
enabling them to perform daily at their arenas for months on end.
PMID- 24352945
TI - Biodiversity and multifunctionality in a microbial community: a novel theoretical
approach to quantify functional redundancy.
AB - Ecosystems have a limited buffering capacity of multiple ecosystem functions
against biodiversity loss (i.e. low multifunctional redundancy). We developed a
novel theoretical approach to evaluate multifunctional redundancy in a microbial
community using the microbial genome database (MBGD) for comparative analysis. In
order to fully implement functional information, we defined orthologue richness
in a community, each of which is a functionally conservative evolutionary unit in
genomes, as an index of community multifunctionality (MF). We constructed a graph
of expected orthologue richness in a community (MF) as a function of species
richness (SR), fit the power function to SR (i.e. MF = cSR(a)), and interpreted
the higher exponent a as the lower multifunctional redundancy. Through a
microcosm experiment, we confirmed that MF defined by orthologue richness could
predict the actual multiple functions. We simulated random and non-random
community assemblages using full genomic data of 478 prokaryotic species in the
MBGD, and determined that the exponent in microbial communities ranged from 0.55
to 0.75. This exponent range provided a quantitative estimate that a 6.6-8.9%
loss limit in SR occurred in a microbial community for an MF reduction no greater
than 5%, suggesting a non-negligible initial loss effect of microbial diversity
on MF.
PMID- 24352946
TI - Does climate limit species richness by limiting individual species' ranges?
AB - Broad-scale geographical variation in species richness is strongly correlated
with climate, yet the mechanisms underlying this correlation are still unclear.
We test two broad classes of hypotheses to explain this pattern. Bottom-up
hypotheses propose that the environment determines individual species' ranges.
Ranges then sum up to yield species richness patterns. Top-down hypotheses
propose that the environment limits the number of species that occur in a region,
but not which ones. We test these two classes of hypotheses using a natural
experiment: seasonal changes in environmental variables and seasonal range shifts
of 625 migratory birds in the Americas. We show that richness seasonally tracks
the environment. By contrast, individual species' geographical distributions do
not. Rather, species occupy different sets of environmental conditions in two
seasons. Our results are inconsistent with extant bottom-up hypotheses. Instead,
a top-down mechanism appears to constrain the number of species that can occur in
a given region.
PMID- 24352947
TI - Sexual selection against natural hybrids may contribute to reinforcement in a
house mouse hybrid zone.
AB - Sexual selection may hinder gene flow across contact zones when hybrid
recognition signals are discriminated against. We tested this hypothesis in a
unimodal hybrid zone between Mus musculus musculus and Mus musculus domesticus
where a pattern of reinforcement was described and lower hybrid fitness
documented. We presented mice from the border of the hybrid zone with a choice
between opposite sex urine from the same subspecies versus hybrids sampled in
different locations across the zone. While no preference was evidenced in
domesticus mice, musculus males discriminated in favour of musculus signals and
against hybrid signals. Remarkably, the pattern of hybrid unattractiveness did
not vary across the hybrid zone. Moreover, allopatric populations tested in the
same conditions did not discriminate against hybrid signals, indicating character
displacement for signal perception or preference. Finally, habituation
discrimination tests assessing similarities between signals pointed out that
hybrid signals differed from the parental ones. Overall, our results suggest that
perception of hybrids as unattractive has evolved in border populations of
musculus after the secondary contact with domesticus. We discuss the mechanisms
involved in hybrid unattractiveness, and the potential impact of asymmetric
sexual selection on the hybrid zone dynamics and gene flow between the two
subspecies.
PMID- 24352948
TI - Adaptive phenotypic plasticity and local adaptation for temperature tolerance in
freshwater zooplankton.
AB - Many organisms have geographical distributions extending from the tropics to near
polar regions or can experience up to 30 degrees C temperature variation within
the lifespan of an individual. Two forms of evolutionary adaptation to such wide
ranges in ambient temperatures are frequently discussed: local adaptation and
phenotypic plasticity. The freshwater planktonic crustacean Daphnia magna, whose
range extends from South Africa to near arctic sites, shows strong phenotypic and
genotypic variation in response to temperature. In this study, we use D. magna
clones from 22 populations (one clone per population) ranging from latitude 0
degrees (Kenya) to 66 degrees North (White Sea) to explore the contributions of
phenotypic plasticity and local adaptation to high temperature tolerance.
Temperature tolerance was studied as knockout time (time until immobilization,
T(imm)) at 37 degrees C in clones acclimatized to either 20 degrees C or 28
degrees C. Acclimatization to 28 degrees C strongly increased T(imm), testifying
to adaptive phenotypic plasticity. At the same time, Timm significantly
correlated with average high temperature at the clones' sites of origin,
suggesting local adaptation. As earlier studies have found that haemoglobin
expression contributes to temperature tolerance, we also quantified haemoglobin
concentration in experimental animals and found that both acclimatization
temperature (AccT) and temperature at the site of origin are positively
correlated with haemoglobin concentration. Furthermore, Daphnia from warmer
climates upregulate haemoglobin much more strongly in response to AccT,
suggesting local adaptation for plasticity in haemoglobin expression. Our results
show that both local adaptation and phenotypic plasticity contribute to
temperature tolerance, and elucidate a possible role of haemoglobin in mediating
these effects that differs along a cold-warm gradient.
PMID- 24352949
TI - Dietary innovations spurred the diversification of ruminants during the
Caenozoic.
AB - Global climate shifts and ecological flexibility are two major factors that may
affect rates of speciation and extinction across clades. Here, we connect past
climate to changes in diet and diversification dynamics of ruminant mammals.
Using novel versions of Multi-State Speciation and Extinction models, we explore
the most likely scenarios for evolutionary transitions among diets in this clade
and ask whether ruminant lineages with different feeding styles (browsing,
grazing and mixed feeding) underwent differential rates of diversification
concomitant with global temperature change. The best model of trait change had
transitions from browsers to grazers via mixed feeding, with appreciable rates of
transition to and from grazing and mixed feeding. Diversification rates in mixed
feeder and grazer lineages tracked the palaeotemperature curve, exhibiting higher
rates during the Miocene thermal maxima. The origination of facultative mixed
diet and grazing states may have triggered two adaptive radiations--one during
the Oligocene-Miocene transition and the other during Middle-to-Late Miocene. Our
estimate of mixed diets for basal lineages of both bovids and cervids is
congruent with fossil evidence, while the reconstruction of browser ancestors for
some impoverished clades--Giraffidae and Tragulidae--is not. Our results offer
model-based neontological support to previous palaeontological findings and
fossil-based hypothesis highlighting the importance of dietary innovations-
especially mixed feeding--in the success of ruminants during the Neogene.
PMID- 24352950
TI - Individual consistency and flexibility in human social information use.
AB - Copying others appears to be a cost-effective way of obtaining adaptive
information, particularly when flexibly employed. However, adult humans differ
considerably in their propensity to use information from others, even when this
'social information' is beneficial, raising the possibility that stable
individual differences constrain flexibility in social information use. We used
two dissimilar decision-making computer games to investigate whether individuals
flexibly adjusted their use of social information to current conditions or
whether they valued social information similarly in both games. Participants also
completed established personality questionnaires. We found that participants
demonstrated considerable flexibility, adjusting social information use to
current conditions. In particular, individuals employed a 'copy-when-uncertain'
social learning strategy, supporting a core, but untested, assumption of
influential theoretical models of cultural transmission. Moreover, participants
adjusted the amount invested in their decision based on the perceived reliability
of personally gathered information combined with the available social
information. However, despite this strategic flexibility, participants also
exhibited consistent individual differences in their propensities to use and
value social information. Moreover, individuals who favoured social information
self-reported as more collectivist than others. We discuss the implications of
our results for social information use and cultural transmission.
PMID- 24352951
TI - Can reduced predation offset negative effects of sea louse parasites on chum
salmon?
AB - The impact of parasites on hosts is invariably negative when considered in
isolation, but may be complex and unexpected in nature. For example, if parasites
make hosts less desirable to predators then gains from reduced predation may
offset direct costs of being parasitized. We explore these ideas in the context
of sea louse infestations on salmon. In Pacific Canada, sea lice can spread from
farmed salmon to migrating juvenile wild salmon. Low numbers of sea lice can
cause mortality of juvenile pink and chum salmon. For pink salmon, this has
resulted in reduced productivity of river populations exposed to salmon farming.
However, for chum salmon, we did not find an effect of sea louse infestations on
productivity, despite high statistical power. Motivated by this unexpected
result, we used a mathematical model to show how a parasite-induced shift in
predation pressure from chum salmon to pink salmon could offset negative direct
impacts of sea lice on chum salmon. This shift in predation is proposed to occur
because predators show an innate preference for pink salmon prey. This preference
may be more easily expressed when sea lice compromise juvenile salmon hosts,
making them easier to catch. Our results indicate how the ecological context of
host-parasite interactions may dampen, or even reverse, the expected impact of
parasites on host populations.
PMID- 24352952
TI - Repeated functional convergent effects of NaV1.7 on acid insensitivity in
hibernating mammals.
AB - Hibernating mammals need to be insensitive to acid in order to cope with
conditions of high CO2; however, the molecular basis of acid tolerance remains
largely unknown. The African naked mole-rat (Heterocephalus glaber) and
hibernating mammals share similar environments and physiological features. In the
naked mole-rat, acid insensitivity has been shown to be conferred by the
functional motif of the sodium ion channel NaV1.7. There is now an opportunity to
evaluate acid insensitivity in other taxa. In this study, we tested for
functional convergence of NaV1.7 in 71 species of mammals, including 22 species
that hibernate. Our analyses revealed a functional convergence of amino acid
sequences, which occurred at least six times independently in mammals that
hibernate. Evolutionary analyses determined that the convergence results from
both parallel and divergent evolution of residues in the functional motif. Our
findings not only identify the functional molecules responsible for acid
insensitivity in hibernating mammals, but also open new avenues to elucidate the
molecular underpinnings of acid insensitivity in mammals.
PMID- 24352953
TI - Effects of lowering dietary fiber before marketing on finishing pig growth
performance, carcass characteristics, carcass fat quality, and intestinal
weights.
AB - A total of 264 pigs (initially 41.0 kg BW) were used in a 90-d study to determine
the effects of lowering dietary fiber before market on pigs fed high dietary
fiber [provided by wheat middlings (midds) and distillers dried grains with
solubles (DDGS)] on growth performance, carcass characteristics, carcass fat
quality, and intestinal weights of growing-finishing pigs. Pens of pigs were
randomly allotted by initial BW and sex to 1 of 6 treatments with 6 replications
per treatment and 7 or 8 pigs per pen. A positive control (corn-soybean meal
based) diet containing no DDGS or midds (9.3% NDF) and a negative control diet
with 30% DDGS and 19% midds (19% NDF) were fed throughout the entire trial (d 0
to 90). The other 4 treatments were arranged in a 2 * 2 factorial with the main
effects of length of fiber reduction (23 or 47 d before marketing) and fiber
level fed during the reduction period (low or medium). Pigs on these treatments
were fed the negative control before the reduction treatment. The medium-fiber
diet contained 15% DDGS and 9.5% midds (14.2% NDF) with the low-fiber diet was
the positive control diet. Increasing the feeding duration of the low-fiber diets
lowered overall ADFI (linear, P = 0.03) and improved G:F (linear, P < 0.01).
Lowering the fiber level for the last 23 d did not influence growth performance;
however, lowering the fiber level improved carcass yield (P = 0.002), with a
greater response (P < 0.001) when the low-fiber diet was fed for 23 d. Jowl fat
iodine value (IV) decreased when the longer lower fiber diets were fed (linear, P
< 0.01) and was lower (P < 0.001) for pigs fed the low-fiber diet during the
fiber reduction period than pigs fed the medium-fiber diet during the same time
period; however, increasing the time lower fiber diets were fed from 23 to 47 d
further reduced (P < 0.01) jowl IV. Increasing the duration that the control diet
was fed by increasing the reduction time from 23 to 47 d increased (P < 0.01)
backfat depth. Reducing the fiber level decreased full large intestine weight
(linear, P = 0.005) with a greater response (P = 0.04) when the low-fiber diet
was fed during the reduction period instead of the medium-fiber diet. In summary,
lowering the fiber level before marketing can improve G:F, carcass yield, carcass
IV, and reduce large intestine weight; however, the optimal duration of the fiber
reduction period depends on the targeted response criteria.
PMID- 24352954
TI - Molecular cloning, sequence analysis, and function of the intestinal epithelial
stem cell marker Bmi1 in pig intestinal epithelial cells.
AB - In the present work, we cloned the full-length cDNA of the pig Bmi1 gene (BMI1
polycomb ring finger oncogene), which has been indicated as an intestinal
epithelial stem cell (IESC) marker in other mammals. This paper provides the
first report of the function of Bmi1 in pig intestinal epithelial cells and a
brief description of its underlying mechanism. Rapid amplification of cDNA ends
technology was used to clone the complete pig Bmi1 sequence, and a Bmi1-pcDNA3.1
vector was constructed for transfection into an intestinal porcine epithelial
cell line (IPEC-1). The proliferation ability of the cells was estimated using
the MTT assay and the EdU incorporation method at different time points after
seeding. Cell cycle information was detected by flow cytometry. The mRNA
abundances of cell cycle-related genes were also measured. The results indicated
that the pig Bmi1 cDNA is 3,193 bp in length and consists of a 981 bp open
reading frame, a 256 bp 5' untranslated region (UTR), and a 1,956 bp 3' UTR. The
transcript contains no signal peptides, and there are no transmembrane regions in
the pig Bmi1 coded protein, which has a total of 326 AA. The overexpression of
the pig Bmi1 in the IPEC-1 cells led to increased cell proliferation and a lower
percentage of cells in the G1 and S phases (P < 0.05), along with a higher
percentage of cells in the G2 phase (P < 0.05). Furthermore, the gene expression
levels of PCNA, Cyclin D1, Cyclin D2, Cyclin B, CDK1, and CDK2 were all elevated
(P < 0.05) by Bmi1 overexpression, while the gene expression levels of Cyclin A2
and p21 showed little difference (P > 0.05). Our data suggested that pig Bmi1 can
increase the proliferation of IPEC-1 cells by promoting the G1/S transition and
the overall cell cycle process.
PMID- 24352955
TI - Evaluation of the efficacy of 2-hydroxy-4-methylselenobutanoic acid on growth
performance and tissue selenium retention in growing pigs.
AB - The aim of this study was to compare the efficacy of a new organic Se (2-hydroxy
4-methylselenobutanoic acid [HMSeBA]) source (SO) with sodium selenite (SS) and
selenized yeast (SY) at various dietary levels for growth performance and tissue
Se deposition in growing pigs. A total of 112 crossbred (Pietrain * [Large White
* Landrace]) gilts were allotted at an average body weight of 26.73 kg to 7
dietary treatments with 8 replicate pens of 2 pigs per pen. Pigs were fed basal
diets unsupplemented or supplemented either with SS, SY, or SO each at 0.1 or 0.3
mg Se/kg of diet for 32 d. Feed intake and BW were recorded during the
experimental period. At the end of the experiment, blood, liver, and psoas major
muscle of all gilts were collected for total Se and relative bioavailability
determination. No differences were observed on final BW, ADG, ADFI, and G:F among
dietary treatments. All Se-supplemented groups exhibited greater total Se
contents in plasma (P < 0.01) and liver (P < 0.01) compared with unsupplemented
control group. However, Se retention in psoas major muscle was improved only when
organic Se source (SY or SO) was added to diets (P < 0.01). Regardless the Se
level, the Se deposition in muscle was greater (P < 0.01) in pigs supplemented
with SO than those supplemented with SY. Slope ratio assay confirmed the greater
bioavailability of Se from organic compared with inorganic Se and also revealed
that the relative bioavailability of Se from HMSeBA for plasma, liver, and muscle
Se response was 170, 141, and 162%, respectively, for SY. This study shows a
potential advantage of HMSeBA supplementation in the increase of Se contents in
pig tissues, indicating that this new organic Se source could be an alternative
source of Se in swine nutrition.
PMID- 24352956
TI - Variation among sows in response to porcine reproductive and respiratory
syndrome.
AB - Porcine reproductive and respiratory syndrome (PRRS) is a viral disease with
negative impacts on reproduction of sows. Genetic selection to improve the
response of sows to PRRS could be an approach to control the disease. Determining
sow response to PRRS requires knowing pathogen burden and sow performance. In
practice, though, records of pathogen burden are unavailable. We develop a
statistical method to distinguish healthy and disease phases and to develop a
method to quantify sows' responses to PRRS without having individual pathogen
burden. We analyzed 10,910 sows with 57,135 repeated records of reproduction
performance. Disease phases were recognized as strong deviation of herd-year-week
estimates for reproduction traits using two methods: Method 1 used raw weekly
averages of the herd; Method 2 used a linear model with fixed effects for
seasonality, parity, and year, and random effects for herd-year-week and sow. The
variation of sows in response to PRRS was quantified using 2 models on the traits
number of piglets born alive (NBA) and number of piglets born dead (LOSS): 1)
bivariate model considering the trait in healthy and disease phases as different
traits, and 2) reaction norm model modeling the response of sows as a linear
regression of the trait on herd-year-week estimates of NBA. The linear model for
NBA had the highest sensitivity (78%) for disease phases. Residual variances of
both were more than doubled in the disease phase compared with the healthy phase.
Trait correlations between healthy and disease phases deviated from unity (0.57
+/- 0.13 - 0.87 +/- 0.18). In the bivariate model, repeatabilities were lower in
disease phase compared with healthy phase (0.07 +/- 0.027 and 0.16 +/- 0.005 for
NBA; 0.07 +/- 0.027 and 0.09 +/- 0.004 for LOSS). The reaction norm model fitted
the data better than the bivariate model based on Akaike's information criterion,
and had also higher predictive ability in disease phase based on cross
validation. Our results show that the linear model is a practical method to
distinguish between healthy and disease phases in farm data. We showed that there
is variation among sows in response to PRRS, implying possibilities for
selection, and the reaction norm model is a good model to study the response of
animals toward diseases.
PMID- 24352957
TI - Development of an antioxidant system after early weaning in piglets.
AB - The objective of this experiment was to investigate oxidative injury and the
development of an antioxidant system after early weaning in piglets. A total of
40 piglets (Landrace* Large White, weaned at 14 d after birth) were randomly
slaughtered 0 (w0d), 1 (w1d), 3 (w3d), 5 (w5d), or 7 d (w7d; n = 8) after
weaning. Concentrations of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8
OHdG), and protein carbonyl and the activities of superoxide dismutase (SOD),
glutathione peroxidase (GSH-Px), and catalase were measured in plasma. Gene
expressions of antioxidant enzymes were determined by quantitative reverse
transcription PCR analysis. The mediation of transcription factor 65 (p65) and
the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways by
oxidative stress was determined by Western blot analysis. Results showed that the
plasma MDA level was significantly higher at 3 d (P < 0.05) and that the protein
carbonyl level increased at 1, 3, and 5 d (P < 0.05) compared with w0d. In
addition, early weaning suppressed the plasma activity of SOD at 1 d (P < 0.05)
and reduced the GSH-Px activity at 3 d (P < 0.05). The expression results in the
jejunum indicate that the genes related to antioxidant enzymes were downregulated
(P < 0.05) at 3 and 5 d after weaning. Uncoupling protein 2 (Ucp2), which is
considered to be a feedback regulation on reactive oxygen species generation,
tended to decrease in the ileum (P < 0.05) after weaning. Tumor protein 53 (p53),
which regulates reactive oxygen species generation, was enhanced (P < 0.05) in
the jejunum after weaning. Meanwhile, early weaning suppressed p65 (at 3, 5, and
7 d; P < 0.05) and Nrf2 (at 5 and 7 d; P < 0.05) signals in the jejunum, which
might feedback-regulate antioxidant gene expression and promote the development
of the antioxidant system. Therefore, we speculate that weaning disrupted
oxidative balance and caused oxidative injury in piglets, and this imbalance can
recover with the development of an antioxidant system via feedback regulation.
PMID- 24352958
TI - The effects of medium-oil dried distillers grains with solubles on growth
performance, carcass traits, and nutrient digestibility in growing-finishing
pigs.
AB - A total of 288 mixed-sex pigs (PIC 327 * 1050; initially 68.9 kg BW) were used in
a 67-d study to determine the effects of increasing medium-oil dried distillers
grains with solubles (DDGS; 7.63% ether extract, 30.1% CP, 19.53% ADF, 36.47%
NDF, and 4.53% ash; as-fed basis) on growth performance and carcass traits in
finishing pigs. Treatments consisted of a corn-soybean meal control diet or the
control diet with 15, 30, or 45% medium-oil DDGS. Diets were fed over 2 phases
(69 to 100 and 100 to 126 kg) and were not balanced for energy. Diets were
formulated to meet or exceed the AA, vitamin, and mineral requirements and
contained constant standardized ileal digestible lysine levels within phase.
Increasing medium-oil DDGS decreased (linear, P < 0.02) ADG and G:F. Average
daily gain decreased approximately 2.3% for every 15% added medium-oil DDGS
whereas G:F decreased approximately 1.3% with every 15% added DDGS. In addition,
final BW, HCW, carcass yield, and loin-eye depth decreased (linear, P < 0.03) and
jowl iodine value (IV) increased (linear, P < 0.001) with increasing medium-oil
DDGS. Nutrient digestibility of the DDGS source was determined using pigs
(initially 25.6 kg BW) that were fed either a corn-based basal diet (96.6% corn
and 3.4% vitamins and minerals) or a DDGS diet, which was a 50:50 blend of the
basal diet and medium-oil DDGS. There were 12 replications for each diet
consisting of a 5-d adaptation period followed by 2 d of total fecal collection
on a timed basis. Feces were analyzed for GE, DM, CP, crude fiber, NDF, ADF, and
ether extract. On an as-fed basis, corn was analyzed to contain 3,871 and 3,515
kcal/kg GE and DE, respectively. Medium-oil DDGS was analyzed to contain 4,585
and 3,356 kcal/kg GE and DE, respectively (as-fed basis). Digestibility
coefficients of the medium-oil DDGS were 70.3% DM, 82.9% CP, 61.4% ether extract,
77.4% ADF, 67.5% NDF, and 67.2% crude fiber. Caloric efficiency (ADFI * kcal
energy intake/kg BW gain) was not different when expressed on a DE or a
calculated ME or NE basis, which suggests that the energy values derived from the
nutrient balance study were accurate. In conclusion, increasing dietary inclusion
of medium-oil DDGS decreased ADG, G:F, final BW, HCW, and carcass yield and
increased jowl fat IV relative to those fed a corn-soybean meal-based diet.
PMID- 24352959
TI - Effects of decreased dietary roughage concentration on energy metabolism and
nutrient balance in finishing beef cattle.
AB - The optimal roughage concentration required in feedlot diets changes continuously
for many reasons such as source, availability, price, and interaction with other
ingredients in the diet. Wet distillers grains and solubles (WDGS) are common in
finishing diets and they contain relatively high amounts of fiber compared with
other grains they replace. Therefore, concentration of roughage could be altered
when WDGS are included in feedlot diets. There has been very little data
published regarding the effects of roughage concentration on energy metabolism
and nutrient balance in beef steers. Therefore, the effects of roughage
concentration in dry-rolled corn (DRC)-based diets containing 25% WDGS were
evaluated in 8 steers (BW = 362 +/- 3.71 kg) using a replicated Latin square.
Data were analyzed with the fixed effects of dietary treatment and period and
random effects of square and steer within square were included in the model.
Diets consisted of 25% WDGS and the balance being DRC and coarsely ground alfalfa
hay (AH) replacing corn at 2% (AH-2), 6% (AH-6), 10% (AH-10), and 14% (AH-14) of
dietary dry matter. As a proportion of GE intake, fecal energy loss increased
linearly (P = 0.02), and DE decreased linearly (P = 0.02) as dietary level of AH
increased. Methane energy loss, as a proportion of GE intake, increased linearly
(P < 0.01) and ME decreased linearly (P < 0.01) as dietary concentration of AH
increased. Heat production tended (P = 0.10) to decrease reaching a minimum of
10% AH and increased from 10 to 14% AH inclusion. Moreover, as a proportion of GE
intake, retained energy (RE) decreased (P < 0.01) as AH level increased in the
diet. Reasons for the decrease in RE are 1) the increase in fecal energy loss
that is associated with decreased ruminal digestibility of NDF when AH replaced
DRC and the shift in ruminal VFA produced, 2) the decreased energy available for
animal retention when NDF increased linearly as AH increased in the diet, and 3)
the methane and heat energy associated with digestion of the fibrous portion of
the AH. Neutral detergent fiber and OM excretion also increased linearly (P <
0.01) with increasing AH in the diet. The increased NDF and OM excretion were
likely caused by the difference in digestibility of AH and DRC.
PMID- 24352960
TI - Influence of supplementation with corn dried distillers grains plus solubles to
growing calves fed medium-quality hay on growth performance and feeding behavior.
AB - To determine the effect of increasing supplementation of corn dried distillers
grains plus solubles (DDGS) on growth performance and feeding behavior, 70 steer
calves (287 +/- 10 kg of BW) were blocked by BW to 3 pens equipped with Insentec
feeders. For 84 d, calves were fed medium-quality grass/legume hay offered for ad
libitum intake and provided 1 of 3 dietary supplemental treatments (n = 7 or 8
steers per treatment within each pen; n = 23 or 24 per treatment): 1) nothing, 2)
DDGS at 0.5% of BW daily (DM basis), and 3) DDGS at 1% of BW daily (DM basis).
Hay intake (kg/d and % of BW daily) decreased linearly (P < 0.001) as DDGS
supplementation increased. Total DMI (kg/d and % of BW) increased linearly (P <
0.001) with DDGS supplementation. Average daily gain and gain efficiency (G:F)
responded quadratically (P <= 0.006) as G:F increased to a lesser extent when
DDGS supplementation increased from 0.5 to 1% than from 0 to 0.5%. Meals (number
per day) and time eating per meal for hay and total diet decreased linearly (P <=
0.006) with increasing DDGS supplementation. Time eating per day for hay
responded quadratically (P < 0.001) and decreased to a greater extent when
increasing from 0 to 0.5% DDGS supplementation than from 0.5 to 1% DDGS. Feed
intake per minute (eating rate) for hay and total diet increased linearly (P <=
0.05) with increasing DDGS supplementation. On d 84, LM area, back fat thickness,
and rump fat thickness increased linearly (P <= 0.006) with increasing DDGS
supplementation. There were significant day * treatment interactions (P < 0.001)
for plasma glucose and urea-N concentrations. Glucose did not change over the
feeding period in control steers but increased in both supplemented groups. Urea
N decreased for control steers over the feeding period whereas urea-N increased
in supplemented steers. In conclusion, supplementation of DDGS in amounts of 0.5
or 1% of BW daily can be used to reduce hay intake and improve ADG and G:F in
growing steers fed medium-quality hay. Additionally, DDGS supplementation alters
feeding behavior.
PMID- 24352961
TI - Impact of diet deprivation and subsequent overallowance during gestation on
mammary gland development and lactation performance.
AB - The impacts of diet deprivation and subsequent overallowance during gestation on
mammary gene expression and development and lactation performance were
determined. Gilts were reared under a conventional (control, CTL; n = 59) or an
experimental (treatment, TRT; n = 56) dietary regimen during gestation. The
experimental regimen provided 70% (restriction diet, RES) and 115% (overallowance
diet, OVER) of the protein and DE contents provided by the CTL diet. The RES diet
was given during the first 10 wk of gestation followed by the OVER diet until
farrowing. Some gilts (14 CTL and 14 TRT) were slaughtered on d 110 of gestation,
and the others were allowed to farrow. Of these remaining sows, 28 (14 CTL and 14
TRT) were slaughtered on d 21 of lactation, and the rest underwent a second
lactation. At each slaughter, mammary tissue was collected for compositional
analyses and assessment of gene expression. Milk samples were collected on d 17
of the first lactation. Litter size was standardized to 11 +/- 1, and piglets
were weighed weekly until d 18 in both parities. The BW and back fat thickness of
TRT first-parity sows were less than those of CTL sows in gestation (P < 0.05),
and their BW was also less in lactation (P < 0.05). The BW of TRT second-parity
sows was still less at mating (P < 0.05) and tended to be less on d 1 of
lactation (P < 0.10) compared with CTL sows. There were no differences in piglet
growth between CTL and TRT litters in either parity, yet mammary development and
mammary gene expression were affected by treatment. There was less parenchymal
tissue (P < 0.01) at the end of the first gestation in TRT than in CTL sows, but
parenchymal tissue composition was not altered by treatment. Relative abundance
of IGF-1 (P < 0.05), ornithine decarboxylase (P < 0.05), signal transducer and
activator of transcription 5B (P < 0.05), and whey acidic protein (WAP, P < 0.01)
genes in parenchyma at the end of the first gestation was lower in TRT than in
CTL sows, and the effect on WAP genes was still present at the end of the first
lactation (P < 0.01). Mammary composition at the end of the first lactation and
milk composition were unaffected by treatment. In conclusion, feed deprivation
and subsequent overallowance in gestation had unfavorable effects on sow BW, back
fat, mammary development, and mammary gene expression at the end of gestation,
but piglet growth rate over the 2 parities was not affected.
PMID- 24352962
TI - Feed preference in pigs: relationship between cereal preference and nutrient
composition and digestibility.
AB - The present work aimed to identify the nutritional characteristics that best
explain cereal feed preference in pigs. A total of 25 cereals of known preference
(at 60% of inclusion in complete feed) from a previous study were evaluated. The
cereals were analyzed for DM, OM, crude fiber, ether extract, CP, GE, digestible
starch, and glycemic index. Additionally, for 12 of the cereals, complete feeds
(the same composition as those previously used to measure preference) were
prepared, analyzed for DM, OM, CP, and starch, and fed to pigs (33 +/- 5.1 kg BW)
fitted with ileal T-cannulae to assess the apparent ileal (AID) and total tract
digestibility (ATTD) of these nutrients using titanium dioxide as an indigestible
marker. The relationships among the different energy and nutrient contents were
studied by principal component (PC) analysis, and the correlations between the
generated PC scores and cereal preference were analyzed. A correlation between
preference and the second PC obtained with data of the 25 cereals was observed (P
< 0.01), which indicated that crude fiber (negatively) and digestible starch, OM,
and glycemic index (positively) were correlated with feed preference.
Statistically significant linear relationships with preference were confirmed for
crude fiber, digestible starch, and glycemic index (R(2) = 0.38, 0.36, and 0.23,
respectively; P < 0.02). Similarly, the first PC obtained with data of the 12
feeds also correlated with preference (P < 0.01), indicating that the digestible
nutrients (positively) and the nondigestible nutrients (negatively) were
correlated with preference. Statistically significant relationships with
preference were observed for the contents of starch (total, digestible AID, and
digestible ATTD: R(2) = 0.62, 0.66, and 0.63, respectively; P < 0.01), AID DM
(digestible and nondigestible: R(2) = 0.41 and 0.44, respectively; P < 0.05),
ATTD DM (digestible and nondigestible: R(2) = 0.67 and 0.70, respectively; P <
0.01), AID OM (digestible and nondigestible: R(2) = 0.45 and 0.43, respectively;
P < 0.05), and ATTD OM (digestible and nondigestible: R(2) = 0.64 and 0.66,
respectively; P < 0.01). It is concluded that cereal preference in pigs is
positively related with their content in digestible nutrients, such as starch,
and negatively related with their nondigestible nutrients, such as crude fiber.
PMID- 24352963
TI - Risk factors associated with health disorders in sport and leisure horses in the
Netherlands.
AB - Horses are used for a wide variety of purposes from being used for recreational
purposes to competing at an international level. With these different uses,
horses have to adapt to numerous challenges and changes in their environment,
which can be a challenge itself in continuously safeguarding their welfare. The
objective of this study was to assess the prevalence of health disorders with
clinical examination and identify possible risk factors of health disorders
affecting horse welfare in professional husbandry systems in the Netherlands.
With the use of fixed protocols for recording health aspects in horses, 150 horse
farms voluntarily participating in the study were assessed by trained assessors.
On each farm, 20 horses were clinically examined, in total almost 3,000 animals.
This study recorded on the basis of the clinical examinations: the respiratory
system (i.e., abnormal breathing [1%], coughing [1%], nasal discharge [1.9%]),
body condition (i.e., 18.8% fat body condition and 6.4% poor body condition),
locomotion (14.5% exhibited irregularity of locomotion and 4.8% were lame), back
palpation (a light response [22.6%] and moderate to severe response [8.4%]),
mouth (i.e., irregularities on mouth corners [3.4%] and bars [3.4%]), and ocular
discharge (12%). Risk factor analysis, stepwise using mixed model regression,
demonstrated several risk factors for health aspects. Horses used for instruction
(riding lessons) were almost two times more at risk to develop moderate to severe
back pain compared to horses used for recreation (odds ratios [OR] = 0.54) or for
competition (OR = 0.61). Horses used for instruction (riding school lessons),
breeding, or recreation all had a higher risk for irregular locomotion or
lameness compared to competition horses (OR = 0.42, OR = 0.55, OR = 2.14,
respectively). Horses used for recreation were more prone to have a higher BCS
compared to horses used for breeding (OR = 3.07) and instruction (OR = 2.06). The
prevalence of health problems and the identified risk factors are valid for the
horses in the present study in which farms voluntarily participated. Furthermore,
the results may provide the basis for horse welfare and health programs on farm
and horse industry levels. With the development of a valid welfare monitoring
system for the horse industry, the welfare of horses can be increased through
improving awareness and stimulating changes in management.
PMID- 24352964
TI - Impact of pig insemination technique and semen preparation on profitability.
AB - Artificial insemination technique and semen preparation impact boar utilization
efficiency, genetic dissemination, and biosecurity. Intrauterine (IUI) and deep
intrauterine (DUI) AI techniques require lower number of spermatozoa per dose
compared to conventional (CON) AI. Frozen semen (FRO) has been associated with
lower reproductive performance compared to fresh semen (FRE) preparation. The
combined effects of 3 AI techniques (CON, IUI, and DUI) and 2 semen preparations
(FRE and FRO) on the financial indicators of a pig crossbreeding system were
studied. A 3-tier system was simulated in ZPLAN and the genetic improvement in a
representative scenario was characterized. The cross of nucleus lines B and A
generated 200,000 BA sows at the multiplier level. The BA sows were inseminated
(CON, IUI, or DUI) with FRE or FRO from line C boars at the commercial level.
Semen preparation and AI technique were represented by distinct sow:boar ratios
in the C * BA cross. A range of farrowing rates (60 to 90%) and litter sizes (8
to 14 liveborn pigs) were tested. Genetic improvement per year for number born
alive, adjusted 21-d litter weight, days to 113.5 kg, backfat, and ADG were 0.01
pigs per litter, 0.06 kg, -0.09 d, -0.29 mm, and 0.88 g, respectively. On
average, the net profit for FRE (FRO) increased (P-value < 0.0001) from CON to
IUI and DUI by 2.2 (3.2%) and 2.6% (4%), respectively. The differences in profit
between techniques were driven by differences in costs. Differences in fixed
costs between IUI and DUI relative to CON were -2.4 (-5.2%) and -3.4% (-7.4%),
respectively. The differences in total costs between FRE and FRO were lower than
5%. The difference in variable costs between FRE and FRO ranged from -5.3 (CON)
to -24.7% (DUI). Overall, insemination technique and semen preparation had a
nonlinear effect on profit. The average relative difference in profit between FRE
and FRO was less than 3% for the scenarios studied.
PMID- 24352965
TI - Effect of Phaffia rhodozyma on performance, nutrient digestibility, blood
characteristics, and meat quality in finishing pigs.
AB - The red yeast, Phaffia rhodozyma (PR), has possible applications as a component
of diets for use in the animal industry. Its primary value lies in its content of
astaxanthin, which has been shown to be an antioxidant several times more
effective than vitamin E. A total of 96 ([Landrace * Yorkshire] * Duroc)
crossbred pigs with an initial BW of 58.61 +/- 3.05 kg were used in this 10-wk
feeding study to determine the effects of PR on growth performance, nutrient
digestibility, blood characteristics, and meat quality in finishing pigs. Pigs
were randomly allotted to 1 of 3 corn-soybean meal-based diets supplemented with
0, 0.1, or 0.2% PR. There were 8 replicate pens per treatment with 4 pigs (2
barrows and 2 gilts) per pen. The inclusion of PR linearly improved G:F in the
phase 1 (P = 0.02), phase 2 (P = 0.02), and during the overall experimental
period (P < 0.01) The DM digestibility was improved in the 0.1% PR treatment in
phase 2 (quadratic, P = 0.01). The white blood cell concentration was increased
in 0.1% PR group (P < 0.05) during phase 2 (quadratic, P < 0.01) and phase 2 (P =
0.04). The inclusion of graded levels of PR linearly increased (P < 0.01) the pH
of LM. The 2-thiobarbituric acid reactive substances were linearly decreased (P =
0.03) by the supplementation of PR. In conclusion, the inclusion of PR could
improve feed efficiency, DM digestibility, and meat quality of the finishing pig.
PMID- 24352966
TI - Effect of reducing dietary protein and lysine on growth performance, carcass
characteristics, intramuscular fat, and fatty acid profile of finishing barrows.
AB - Intramuscular fat is an important quality trait in pork. Lysine and protein have
been reported to influence this trait, but most studies have modified both
factors simultaneously. In this study, the effects of dietary Lys and protein
were investigated in finishing pigs to determine if either of the 2 factors alone
or in combination influence the deposition of intramuscular fat. One hundred and
four barrows (Landrace * Duroc) were fed 1 of 4 experimental diets, including
control protein-control Lys (CPCL), control protein-low Lys (CPLL), low protein
control Lys (LPCL), and low protein-low Lys diets (LPLL) with 10 pens per
treatment and 2 or 3 pigs per pen. Pigs fed CPLL showed a trend to decrease feed
efficiency (P < 0.10) compared with those fed CPCL, but pigs fed LPLL performed
similarly to the CPCL pigs, indicating that CP levels can be reduced to 12% for
pigs between 62 and 97 kg and to 9.8% afterward without negative effects on
performance. In the longissimus thoracis, intramuscular fat increased in pigs fed
LPCL or CPLL (P < 0.05) compared with CPCL. In the semimembranosus muscle,
intramuscular fat was reduced in pigs fed LPLL compared with those fed CPLL (P <
0.05), and the same trend was observed in the longissimus thoracis (P < 0.10).
Dietary protein reduction tended to increase back fat thickness (P < 0.10) and
reduced SFA and MUFA (P < 0.05) and PUFA, particularly in subcutaneous fat (P <
0.05), whereas the effect on MUFA in the longissimus thoracis was less
pronounced. A reduction of n-3 FA (P < 0.05) and PUFA (P < 0.01) in the
semimembranosus muscle and in the liver, respectively, was observed when the
level of dietary protein was reduced. These results indicate that the effect of a
reduction of dietary protein and Lys on growth and intramuscular fat is not
independent, and reduction of protein, while maintaining Lys, may improve meat
quality without impairing performance.
PMID- 24352967
TI - Investigation of bacterial diversity in the feces of cattle fed different diets.
AB - The objective of this study is to investigate individual animal variation of
bovine fecal microbiota including as affected by diets. Fecal samples were
collected from 426 cattle fed 1 of 3 diets typically fed to feedlot cattle: 1)
143 steers fed finishing diet (83% dry-rolled corn, 13% corn silage, and 4%
supplement), 2) 147 steers fed late growing diet (66% dry-rolled corn, 26% corn
silage, and 8% supplement), and 3) 136 heifers fed early growing diet (70% corn
silage and 30% alfalfa haylage). Bacterial 16S rRNA gene amplicons were
determined from individual fecal samples using next-generation pyrosequencing
technology. A total of 2,149,008 16S rRNA gene sequences from 333 cattle with at
least 2,000 sequences were analyzed. Firmicutes and Bacteroidetes were dominant
phyla in all fecal samples. At the genus level, Oscillibacter, Turicibacter,
Roseburia, Fecalibacterium, Coprococcus, Clostridium, Prevotella, and
Succinivibrio were represented by more than 1% of total sequences. However,
numerous sequences could not be assigned to a known genus. Dominant unclassified
groups were unclassified Ruminococcaceae and unclassified Lachnospiraceae that
could be classified to a family but not to a genus. These dominant genera and
unclassified groups differed (P < 0.001) with diets. A total of 176,692
operational taxonomic units (OTU) were identified in combination across all the
333 cattle. Only 2,359 OTU were shared across 3 diet groups. UniFrac analysis
showed that bacterial communities in cattle feces were greatly affected by
dietary differences. This study indicates that the community structure of fecal
microbiota in cattle is greatly affected by diet, particularly between forage-
and concentrate-based diets.
PMID- 24352968
TI - An evaluation of the effects of added vitamin D3 in maternal diets on sow and pig
performance.
AB - A total of 84 sows (PIC 1050) and their litters were used to determine the
effects of supplementing maternal diet with vitamin D3 on sow and pig
performance, serum 25-hydroxyvitamin D3 (25(OH)D3), milk vitamin D3, neonatal
bone mineralization, and neonatal tissue vitamin D3. After breeding, sows were
randomly assigned to 1 of 3 dietary vitamin D3 treatments (1,500, 3,000, or 6,000
IU/kg of complete diets). Sows were bled on d 0 and 100 of gestation and at
farrowing and weaning (d 21). Pig BW was recorded at birth and weaning, and serum
was collected from 2 pigs/litter at birth, on d 10 and at weaning. A total of 54
pigs (18/treatment) were euthanized at birth and necropsied to sample bones and
tissues. Sow and suckling pig performance and neonatal bone ash and bone density
did not differ among maternal vitamin D3 treatments; however, sow 25(OH)D3 and
milk vitamin D3 increased (linear, P < 0.01) with increasing maternal vitamin D3
supplementation. Piglet serum 25(OH)D3 increased (quadratic, P < 0.03) with
increased maternal vitamin D3. Neonatal kidney vitamin D3 tended (quadratic, P =
0.08) to decrease with increasing maternal vitamin D3, but liver vitamin D3
tended (linear, P = 0.09) to increase with increasing maternal vitamin D3. At
weaning, a subsample of 180 pigs (PIC 327 * 1050) were used in a 3 * 2 split plot
design for 35 d to determine the effects of maternal vitamin D3 and 2 levels of
dietary vitamin D3 (1,800 or 18,000 IU/kg) from d 0 to 10 postweaning on nursery
growth and serum 25(OH)D3. Overall (d 0 to 35), nursery ADG and G:F were not
affected by either concentration of vitamin D3, but ADFI tended (quadratic, P <
0.06) to decrease with increasing maternal vitamin D3 as pigs from sows fed 3,000
IU had lower ADFI compared with pigs from sows fed 1,500 or 6,000 IU/kg. Nursery
pig serum 25(OH)D3 increased with increasing maternal vitamin D3 (weaning) on d 0
(linear, P < 0.01), and maternal * diet interactions (P < 0.01) were observed on
d 10 and 21 because pigs from sows fed 1,500 IU had greater increases in serum
25(OH)D3 when fed 18,000 IU compared with pigs from sows fed 3,000 IU. In
conclusion, sow and pig serum 25(OH)D3, milk vitamin D3, and neonatal tissue
vitamin D3 can be increased by increasing maternal vitamin D3, and nursery pig
25(OH)D3 can be increased by increasing dietary vitamin D3; however, sow and pig
performance and neonatal bone mineralization was not influenced by increasing
vitamin D3 dietary levels.
PMID- 24352969
TI - Effects of dietary sulfur concentration and forage-to-concentrate ratio on
ruminal fermentation, sulfur metabolism, and short-chain fatty acid absorption in
beef heifers.
AB - This study evaluated the effects of dietary S concentration and forage-to
concentrate ratio (F:C) on ruminal fermentation, S metabolism, and short-chain
fatty acid (SCFA) absorption in beef heifers. Sixteen ruminally cannulated
heifers (initial BW 628 +/- 48 kg) were used in a randomized complete block
design with a 2 * 2 factorial treatment arrangement. The main factors included
F:C (4% forage vs. 51% forage, DM basis) and the S concentration, which was
modified using differing sources of wheat dried distillers grains with solubles
(DDGS) to achieve low- and high-S diets (LS = 0.30% vs. HS = 0.67% S on a DM
basis). Elemental S was also added to increase the S content for the HS diets.
Serum sulfate concentration from blood, sulfide (S(2-)), and SCFA concentrations
from ruminal fluid, hydrogen sulfide (H2S) concentration from the ruminal gas
cap, and urinary sulfate concentration were determined. Continuous rumen pH and
SCFA (acetate, butyrate, and propionate) absorption were measured. There were no
interactions between S concentration and F:C. The F:C did not affect DMI (P =
0.26) or ruminal S metabolite concentrations (P >= 0.19), but ruminal pH was
lower (P < 0.01) and SCFA absorption was greater (P < 0.01) for low F:C diets.
Heifers fed HS diets had less DMI (P < 0.01) but greater ruminal pH (P < 0.01),
greater concentrations of ruminal H2S (P < 0.01) and serum sulfate (P < 0.01),
and greater urinary sulfate concentration (P < 0.01) and output (P < 0.01)
relative to heifers fed LS diets. Ruminal H2S was positively correlated with
serum sulfate (r = 0.89; P < 0.01). Ruminal acetate concentration was not
affected (P = 0.26) by dietary S concentration. Heifers fed the HS diet had lower
(P = 0.01) ruminal propionate concentration and tended to have lower (P = 0.06)
butyrate concentration than heifers fed the LS diet. Ruminal acetate was greater
(P = 0.01) and butyrate was less (P < 0.01) with the high F:C diet than the low
F:C diet. Both HS (P = 0.06) and low F:C (P = 0.07) diets tended to reduce urine
output. Feeding HS diets reduced SCFA absorption (P < 0.05). In summary, S
metabolism in beef heifers was not influenced by the F:C, but HS reduced DMI,
inhibited SCFA absorption, and increased urinary S excretion.
PMID- 24352970
TI - Transit effects on fecal Escherichia coli O157 prevalence and coliform
concentrations in feedlot cattle.
AB - Our objectives were to evaluate the effects of transportation and lairage on
fecal shedding of Escherichia coli O157 (E. coli O157), total Escherichia coli,
and total coliforms in feedlot cattle, and the relationships between E. coli O157
prevalence and total E. coli population. The study was a randomized complete
block design with a split-plot including 2 treatments: a nontransported group,
which remained in its pen at all times, and a transported group, which was
transported for 1 h in a trailer and subsequently unloaded in a different pen.
The experiment was repeated on 3 different days (blocking factor) with 20
steers/d (10 steers/treatment, 60 total). Fecal samples were taken pretransport
(h 0) and after 4 and 28 h, lairage from freshly voided fecal pats were taken
from each animal. One gram of feces was transferred to a PBS tube, serially
diluted, and plated onto Petrifilm for enumeration of total coliforms. Another
sample (1 g) was added to gram-negative broth containing cefixime, cefsulodin,
and vancomycin, and subjected to immunomagnetic separation. Resulting beads were
plated onto MacConkey agar with sorbitol, cefixime, and tellurite. Nonsorbitol
fermenting colonies were selected and tested for indole production and O157
antigen agglutination. Results were confirmed using an API 20E kit. Prevalence of
E. coli O157 was transient across blocks. E. coli O157 prevalence revealed no
treatment * sampling time interaction (P = 0.179) or sampling time effect (P =
0.937), but a tendency for a treatment effect (P = 0.092). Numbers of E. coli and
other coliforms did not change across blocks. No effect of treatment (P > 0.7)
was observed on total E. coli concentrations or total coliforms. However,
tendencies for treatment * sampling time interactions were observed on both
populations (P < 0.08), as well as a tendency for a sampling time effect on total
E. coli (P = 0.087) and an effect on total coliforms (P = 0.004). Prevalence of
E. coli O157 was not correlated with the concentration of total E. coli (P =
0.954). Results suggest that shedding of E. coli O157 and coliforms can vary
within a period of 29 h. Greater statistical power and pathogen quantification,
as well as hide sampling and stress-related measurements, are needed to be able
to conclude on the effects of transport stress on E. coli O157 prevalence and the
changes undergone in pathogen shedding patterns after transportation.
PMID- 24352972
TI - Energy efficiency of growing ram lambs fed concentrate-based diets with different
roughage sources.
AB - Poor-quality roughages are widely used as fiber sources in concentrate-based
diets for ruminants. Because roughage quality is associated with the efficiency
of energy use in forage-based diets, the objective of this study was to determine
whether differing the roughage source in concentrate-based diets could change the
energy requirements of growing lambs. Eighty-four 1/2 Dorper * 1/2 Santa Ines ram
lambs (18.0 +/- 3.3 kg BW) were individually penned and divided into 2 groups
according to primary source of dietary roughage: low-quality roughage (LQR;
sugarcane bagasse) or medium-quality roughage (MQR; coastcross hay). Diets were
formulated to be isonitrogenous (2.6% N) and to meet 20% of physically effective
NDF. After a 10-d ad libitum adaptation period, 7 lambs from each group were
randomly selected and slaughtered (baseline). Twenty-one lambs in each diet group
were fed ad libitum and slaughtered at 25, 35, or 45 kg BW. The remaining 28
lambs (14 from each diet group) were submitted to 1 of 2 levels of feed
restriction: 70% or 50% of the ad libitum intake. Retentions of body fat, N, and
energy were determined. Additionally, 6 ram lambs (44.3 +/- 5.6 kg BW) were kept
in metabolic cages and used in a 6 * 6 Latin square experiment designed to
establish the ME content of the 2 diets at the 3 levels of DM intake. There was
no effect of intake level on diet ME content, but it was greater in the diet with
LQR than in the diet with MQR (3.18 vs. 2.94 Mcal/kg, respectively; P < 0.01).
Lambs fed the diet with LQR had greater body fat (g/kg of empty BW) and energy
concentrations (kcal/kg of empty BW) because of a larger visceral fat deposition
(P < 0.05). Using a low-quality roughage as a primary source of forage in a
concentrate-based diet for growing lambs did not change NEm and the efficiency of
ME use for maintenance, which averaged 71.6 kcal/kg(0.75) of shrunk BW and 0.63,
respectively. On the other hand, the greater nonfibrous carbohydrate content of
the diet with LQR resulted in a 17% better efficiency of ME use for gain (P <
0.01), which was associated with a greater partial efficiency of energy retention
as fat (P < 0.01). This increased nutritional efficiency, however, should be
viewed with caution because it is related to visceral fat deposition, a nonedible
tissue.
PMID- 24352974
TI - Anomalous left main coronary artery originating from the pulmonary artery.
PMID- 24352973
TI - Baseline health perceptions, dysphagia, and survival in patients with head and
neck cancer.
AB - BACKGROUND: In head and neck cancer patients prior to treatment, dysphagia noted
by patients is more common than aspiration on formal swallow studies. The authors
hypothesized that patient-reported dysphagia impacts multiple domains of quality
of life (QOL) and predicts disease recurrence and disease-related death. METHODS:
The Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, and the
EuroQOL-5D-3L were administered to 159 patients before treatment with curative
intent in this prospective cohort study. Logistic regression analysis evaluated
associations among clinical and subjective measures. Multivariable competing risk
regression tested the impact of clinical, tumor, and patient-reported measures on
survival. RESULTS: Baseline dysphagia, pain, and diminished patient-reported
health state were found to be closely associated with weight loss before
treatment and advanced T classification. However, only 58% of patients (23 of 40
patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found
to be associated with pain and/or diminished patient-reported health state,
independent of weight loss. Female patients were more likely to report pain and
dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to
be predictive of disease recurrence and disease-related death, adjusting for T
and N classifications, ECOG performance status, smoking status, and weight loss,
and accounting for competing risks of death (recurrence-free survival: hazards
ratio, 3.8 [95% confidence interval, 1.7-8.4; P = .001] and disease-related
death: hazards ratio, 4.2 [95% confidence interval, 1.04-5; P = .004]).
CONCLUSIONS: Baseline dysphagia affects multiple domains of QOL and general
health perceptions in patients with head and neck cancer prior to treatment. A
dysphagia measure captures the effort of maintaining nutrition, and identifies
patients predisposed to disease recurrence and disease-related death.
PMID- 24352975
TI - Clinical application of the Provox NiD voice prosthesis: a longitudinal study.
AB - OBJECTIVES/HYPOTHESIS: To evaluate the indications, complications, and device
life of the Provox NiD in a large cohort at a tertiary US cancer center. STUDY
DESIGN: Longitudinal retrospective cohort study. METHODS: We reviewed the records
of patients who used the NiD prosthesis (2005-2011) for general indicators,
device life, and complications. RESULTS: One hundred eighty-six patients who used
the NiD were included (median follow-up: 21.4 months). The NiD was placed at
initial fit in 41 (22%) patients, whereas 145 (78%) tried an NiD after using
another type of prosthesis. Most patients used the NiD similarly to an indwelling
device. Median NiD device life was significantly longer than that of other
nonindwelling prostheses (45 vs. 29 days, P=.0061), and did not significantly
differ from that of standard indwelling devices (45 vs. 50 days, P=.4263). Thirty
eight percent (71 of 189) of NiD users had a history of early leakage (<8 weeks)
using a different prosthesis before trying the NiD. Among patients with a pre
existing history of early leakage, almost 90% of NiD prostheses outperformed the
device life of other products. CONCLUSIONS: The NiD prosthesis offers
satisfactory device life on a par with indwelling prostheses in our cohort of NiD
users. Coupled with favorable published airflow characteristics and satisfactory
tracheoesophageal voice, these data suggest that the NiD offers a durable, low
cost prosthetic alternative in contemporary practice. A unique indication for NiD
may be improved device life in some patients with a history of early leakage.
LEVEL OF EVIDENCE: 4.
PMID- 24352976
TI - Fe5C2 nanoparticles with high MRI contrast enhancement for tumor imaging.
AB - An ancient material for magnetic resonance (MR) imaging: For the first time,
Fe5C2 is prepared as colloidal stable nanoparticles with good aqueous stability.
The nanoparticles boast strong magnetization, excellent chemical inertness, low
toxicity, and one of the highest r2 relaxivities reported to date. These
nanoparticles hold great potential in MR imaging as well as in other biomedical
areas.
PMID- 24352978
TI - Alternol induces an S-phase arrest of melanoma B16F0 cells.
AB - Alternol is a novel compound purified from the fermentation products of a
microorganism in the yew tree bark. This study looks at the effects of alternol
on the proliferation and cell cycle distribution of mouse melanoma cells. The
inhibition of cell proliferation and changes in cell cycle distribution were
analysed by sulforhodamine B and flow cytometry assays, respectively. mRNA
expression of cyclin A, cyclin-dependent kinase 2 (CDK2), proliferating cell
nuclear antigen (PCNA) and CDK inhibitor1A (p21) were measured by real-time
reverse transcription PCR (RT-PCR). The protein levels of cyclin A, CDK2 and PCNA
were analysed by Western blot analysis. p21 was measured by ELISA. Alternol
treatment caused a significant decrease in the proliferation rate of B16F0 and
B16F10 cells, which were significantly arrested in S phase, but this treatment
had less effect on normal human embryonic kidney 293T cells. The mechanism by
which alternol inhibits B16F0 proliferation in vitro may be associated with the
inhibition of CDK2 and PCNA, and the activation of p21.
PMID- 24352979
TI - Inversion of supramolecular helicity in oligo-p-phenylene-based supramolecular
polymers: influence of molecular atropisomerism.
AB - The helical organization of oligo-p-phenylene-based organogelators has been
investigated by atomic force microscopy, circular and vibrational circular
dichroism, and Raman techniques. Whilst OPPs with more than two phenyl rings in
the core self-assemble into left-handed helices, that with a biphenyl core shows
an inversion of the supramolecular helicity depending on the formation conditions
through the atropisomerism of the biphenyl central unit. The results presented
herein outline a new example of kinetically controlled modulation of
supramolecular helicity.
PMID- 24352977
TI - Cryptogenic stroke-the appropriate diagnostic evaluation.
AB - OPINION STATEMENT: Ischemic strokes are a significant cause of morbidity and
mortality in the United States. They may be due to large artery atherosclerosis,
small vessel occlusion, cardioembolism, or other less common mechanisms such as
toxins, hypercoagulable disorders, and vasospasm. Each mechanism carries its own
risk of recurrence and prognosis. Strokes without an identifiable cause despite a
complete work-up are described as cryptogenic. Cryptogenic stroke therefore is a
diagnosis of exclusion, and one that should not be arrived at haphazardly. One
must complete a thorough, and frequently challenging, stroke work-up prior to
this diagnosis. Challenges in determining stroke etiology include the transient
nature of precipitating events such as vasospasm or cardiac arrhythmias, variable
durations of cardiac monitoring, and unclear significance of certain cardiac
structural anomalies. Many consider cryptogenic stroke to be a heterogeneous
combination of paroxysmal and occult conditions that create such diagnostic
difficulties. The diagnosis of cryptogenic stroke itself carries with it specific
outcomes and prognosis. This article will provide an overview of the definition
and epidemiology, recommendations for diagnostic evaluation, and risks of
recurrence of cryptogenic stroke.
PMID- 24352983
TI - Broadband all-dielectric magnifying lens for far-field high-resolution imaging.
AB - A transformation-optics magnifying lens is reported in the microwave frequency,
which is made of inhomogeneous but isotropic dielectrics to reach impedance
matching. The authors demonstrate the broadband subwavelength imaging performance
and magnification factor experimentally from the far-field radiation patterns.
PMID- 24352984
TI - Broadband light extraction from white organic light-emitting devices by employing
corrugated metallic electrodes with dual periodicity.
AB - A dual-periodic corrugation consisting of two sets of gratings with different
periods to realize a broadband light extraction in white organic light-emitting
diodes (WOLEDs) is shown. A 37% enhancement in current efficiency and 48%
enhancement in the external quantum efficiency compared to those of the
conventional planar devices have been obtained. Besides the much improved
efficiency, the dual-periodic corrugated WOLEDs exhibit satisfying viewing
characteristics.
PMID- 24352985
TI - Design of radiation tolerant materials via interface engineering.
AB - A novel interface engineering strategy is proposed to simultaneously achieve
superior irradiation tolerance, high strength, and high thermal stability in bulk
nanolayered composites of a model face-centered-cubic (Cu)/body-centered-cubic
(Nb) system. By synthesizing bulk nanolayered Cu-Nb composites containing
interfaces with controlled sink efficiencies, a novel material is designed in
which nearly all irradiation-induced defects are annihilated.
PMID- 24352987
TI - Brown recluse spider's nanometer scale ribbons of stiff extensible silk.
AB - The silk of the recluse spider features a ribbon-like morphology unlike any other
spider silk or synthetically spun polymer fiber. These protein ribbons represent
free-standing polymer films with a thickness of about 50 nm. Stress-strain
characterization of individual fibers via atomic force microscopy reveals that
these ribbons, only a few molecular layers of protein thin, rival the mechanical
performance of the best silks.
PMID- 24352990
TI - The wide-area medical transportation following the Great East Japan Earthquake:
the Japanese government's control and coordination.
PMID- 24352991
TI - Effective purpose in transnational humanitarian healthcare providers.
AB - OBJECTIVE: To advance knowledge regarding the education and support needs of
staff deployed to international settings from a US academic medical center (AMC).
DESIGN: A qualitative approach rooted in phenomenology called, Transcendental
Method for Research with Human Subjects was used. A flexible interview guide was
used to guide participants into self-reflection about the decision to participate
in global healthcare, educational preparation, field experiences, and return.
SETTING: The study was conducted at a US AMC. PARTICIPANTS: Sample size was 15
and included nurses, physicians, and therapists who had participated in disaster
and/or developmental humanitarian global health deployments. Purposive sampling
with a maximum variation approach was used along with snowball sampling. Sample
size was determined by reaching horizonal understanding of participants. MAIN
OUTCOME MEASURES: The study sought to elicit and analyze responses from
participants in an open-ended manner. RESULTS: Analysis revealed the following
seven themes: a) the yearning to relieve suffering, b) getting ready, c) making a
difference, d) bad things happening to wonderful people, e) challenging and
sustaining factors, f) dialectical alienation, and g) knowing what really
matters. The concept of "effective purpose" emerged from interpretation of these
themes. CONCLUSIONS: Most participants found their experiences to be beneficial
and meaningful but faced challenges in the field. Knowledge and skills varied
among providers. Education and support are critical for healthcare professionals
who engage in transnational healthcare. Recommendations for staff preparation are
provided.
PMID- 24352992
TI - Health consequences of involuntary exposure to benzene following a flaring
incident at British Petroleum refinery in Texas City.
AB - OBJECTIVE: Environmental exposure to benzene can lead to deleterious effects on
many biological systems including blood-forming organs, liver, and kidneys. The
authors sought to investigate the health consequences of benzene exposure
following a flaring incident that occurred at the British Petroleum (BP) refinery
in Texas City, TX. SUBJECTS AND PARTICIPANTS: A cohort of subjects who were
exposed to a daily sustained release of toxic chemicals including more than 7,711
kg (17,000 lb) of benzene for a total duration of 40 days due to BP's flaring
incident. INTERVENTIONS: Not applicable to an observational study. METHODS:
Subjects who underwent physical and clinical evaluation between June 2010 and
October 2012 were included. Demographic and clinical laboratory data were
collected and analyzed. Hematologic data such as white blood cell (WBC) counts,
platelet counts, hemoglobin, hematocrit, blood urea nitrogen (BUN), and
creatinine levels in the serum were evaluated. In addition, data on alkaline
phosphatase (ALP), aspartate amino transferase (AST), and alanine amino
transferase (ALT) levels in the serum were examined. Urinary phenol was evaluated
as a benzene metabolite. The outcomes were compared between exposed and unexposed
patients. RESULTS: A total of 200 subjects (benzene exposed, n = 100 and
unexposed, n = 100) were included. Benzene exposed subjects showed significantly
higher levels of WBC (*10(3) per MUL) count (8.6 +/- 5.4 vs 6.5 +/- 2.0, p =
0.0003) and platelet (*10(3) per MUL) count (291.3 +/- 82.7 vs 264.1 +/- 74.0, p
= 0.0076) compared with the unexposed subjects. ALP (IU/L) was significantly
elevated in the benzene exposed subjects compared with the unexposed subjects
(121.2 +/- 73.7 vs 65.4 +/- 23.6, p = 0.000). Similarly, benzene exposed subjects
had significantly higher levels of AST (IU/L) compared with unexposed subjects
(23.4 +/- 11.8 vs 19.5 +/- 8.9, p = 0.0089). CONCLUSION: This retrospective pilot
study found that environmental benzene exposure from the BP's flaring incident
appears to pose significant health risks including specific alteration of blood
cells and liver enzymes, indicating that subjects exposed to benzene may be at a
higher risk of developing hepatic or blood related disorders.
PMID- 24352993
TI - Innovations in point-of-care testing for enhanced United States disaster caches.
AB - OBJECTIVE: To describe, innovate, recommend, and foster the implementation of
point-of-care (POC) testing in disaster caches to enhance crisis standards of
care and to improve triage, diagnosis, monitoring, treatment, and management of
victims and volunteers in complex emergencies and disasters. DESIGN AND SETTINGS:
The authors compared POC testing in United States disaster caches to commercially
available POC testing to enhance the caches and to reflect current state-of-the
art diagnostic capabilities. The authors also provided recommendations based on
literature review and knowledge from newly developed POC technologies from the UC
Davis Point-of-Care Technologies Center. RESULTS: Presently, US POC testing
caches comprise chemistry/electrolytes, pregnancy, hemoglobin, cardiac
biomarkers, hematology, fecal occult blood, drugs of abuse, liver function, blood
gases, and limited infectious diseases. Deficiencies with existing POC tests for
cardiac biomarkers, hematology, and infectious diseases should be eliminated. POC
resources can be customized for pandemics, complex emergencies, or disasters
based on geographic location and potential infectious diseases. Additionally, a
new thermally stabilized container can help alleviate environmental stresses that
reduce test quality. CONCLUSIONS: Innovations in POC technologies can improve
response preparedness with enhanced diagnostic capabilities. Several innovations,
such as the i-STAT(r) Wireless, OraQuick ADVANCE(r) HIV-1/2, VereTropTM Lab-on-a
Chip, and new compact hematology analyzers will improve test clusters that
facilitate evidence-based decision making and crisis standards of care during US
national disaster responses. Additionally, strategic resources and operator
training should be globally harmonized to improve the efficiency of international
responses.
PMID- 24352994
TI - Effects of environmental conditions on point-of-care cardiac biomarker test
performance during a simulated rescue: implications for emergency and disaster
response.
AB - OBJECTIVE: To characterize the effects of environmental stress on point-of-care
(POC) cardiac biomarker testing during a simulated rescue. DESIGN: Multiplex test
cassettes for cardiac troponin I (cTnI), brain natriuretic peptide (BNP), CK-MB,
myoglobin, and D-dimer were exposed to environmental stresses simulating a 24
hour rescue from Hawaii to the Marshall Islands and back. We used Tenney
environmental chambers (T2RC and BTRC) to simulate flight conditions (20 degrees
C, 10 percent relative humidity) and ground conditions (22.3-33.9 degrees C, 73
77 percent). We obtained paired measurements using stressed versus control (room
temperature) cassettes at seven time points (T1-7 with T1,2,6,7 during flight and
T3-5 on ground). We analyzed paired differences (stressed minus control) with
Wilcoxon signed rank test. We assessed the impact on decision-making at clinical
thresholds. RESULTS: cTnI results from stressed test cassettes (n = 10) at T4 (p
< 0.05), T5 (p < 0.01), and T7 (p < 0.05) differed significantly from control,
when testing samples with median cTnI concentration of 90 ng/L. During the ground
rescue, 36.7 percent (11/30) of cTnI measurements from stressed cassettes
generated significantly lowered results. At T5, 20 percent (2/10) of cTnI results
were highly discrepant-stressed cassettes reported normal results, when control
results were >100 ng/L. With sample median concentration of 108 pg/mL, BNP
results from stressed test cassettes differed significantly from controls (p <
0.05). CONCLUSION: Despite modest, short-term temperature elevation,
environmental stresses led to erroneous results. False negative cTnI and BNP
results potentially could miss acute myocardial infarction and congestive heart
failure, confounded treatment, and increased mortality and morbidity. Therefore,
rescuers should protect POC reagents from temperature extremes.
PMID- 24352995
TI - Simple, school-based mass distribution as a small-town strategy.
AB - OBJECTIVE: Test a radically simple school-based point-of-dispensing model.
DESIGN: Prospective study. SETTING: Community PARTICIPANTS: Community residents
with children at one middle school. INTERVENTIONS: Rapid dispensing of
medication. MAIN OUTCOME MEASURE(S): 1) Measure and extrapolate ability to
distribute medications to Darien residents through school-based distribution
model; 2) assess if using a limited staffing model with limited training was
functional. Identify stress points; 3) understand the existing school
communication model; 4) track and extrapolate the breakdown of adult-to-child
doses distributed and compare to existing census data; and 5) measure throughput
of school-based distribution model in the 50-minute drop-off period. RESULTS: 1)
This exercise supported the concept that rapid medication distribution through
the public schools is an appropriate strategy for health departments,
particularly departments with limited resources. 2) Just-in-time briefing worked
well as a training strategy. The primary stress points identified were in restock
if medication was in blister packs, we would not be able to stock vests with 100
of each as they are substantially bigger than mints. 3) The secure Darien Public
School notification system was ideal for distributing information to parents
since they tend to receive school communication on a regular basis and by
definition, access is limited to town residents. 4) When asked about household
size, most drivers indicated "two adults and two (or more) children." We
distributed medication for 784 adults and 963 children. This ratio was higher
than the 2010 Census, which had an average household size of 3.08 in Darien. 5)
In 50 minutes, using a mix of Health Department and school staff, medication was
distributed to 1,747 residents, almost 10 percent of the population. The hourly
throughput from this model was distribution to 2,096 people per hour or 699
people per distributor per hour. This compares favorably to almost every other
nonmedical distribution model. CONCLUSIONS: Using four Health Department staff
and six public school staff, we distributed medication to 784 adults and 963
pediatric residents in 50 minutes at one school. If we extrapolated that across
the six other public schools in Darien, we could provide medication to more than
10,000 residents within 8 hours. While we are cognizant of the limitations and
drawbacks of this model, we strongly believe that it is the only practical
solution to the problem of rapid distribution of medication to the entire
community.
PMID- 24352996
TI - High-throughput direct fecal PCR assay for detection of Mycobacterium avium
subsp. paratuberculosis in sheep and cattle.
AB - Johne's disease (JD) is a chronic enteric disease caused by Mycobacterium avium
subsp. paratuberculosis that affects ruminants. Transmission occurs by the fecal
oral route. A commonly used antemortem diagnostic test for the detection of M.
avium subsp. paratuberculosis in feces is liquid culture; however, a major
constraint is the 2- to 3-month incubation period needed for this method. Rapid
methods for the detection of M. avium subsp. paratuberculosis based on PCR have
been reported, but comprehensive validation data are lacking. We describe here a
new test, the high-throughput-Johnes (HT-J), to detect M. avium subsp.
paratuberculosis in feces. Its diagnostic accuracy was compared with that of
liquid radiometric (Bactec) fecal culture using samples from cattle (1,330
samples from 23 herds) and sheep (596 samples from 16 flocks). The multistage
protocol involves the recovery of M. avium subsp. paratuberculosis cells from a
fecal suspension, cell rupture by bead beating, extraction of DNA using magnetic
beads, and IS900 quantitative PCR. The limit of detection of the assay was 0.0005
pg, and the limit of quantification was 0.005 pg M. avium subsp. paratuberculosis
genomic DNA. Only M. avium subsp. paratuberculosis was detected from a panel of
51 mycobacterial isolates, including 10 with IS900-like sequences. Of the 549
culture-negative fecal samples from unexposed herds and flocks, 99% were negative
in the HT-J test, while 60% of the bovine- and 84% of the ovine-culture-positive
samples were positive in the HT-J test. As similar total numbers of samples from
M. avium subsp. paratuberculosis-exposed animals were positive in culture and HT
J tests in both species, and as the results of a McNemar's test were not
significant, these methods probably have similar sensitivities, but the true
diagnostic sensitivities of these tests are unknown. These validation data meet
the consensus-based reporting standards for diagnostic test accuracy studies for
paratuberculosis and the Minimum Information for Publication of Quantitative Real
Time PCR Experiments (MIQE) guidelines (S. A. Bustin et al., Clin. Chem. 55:611
622, 2009, doi:10.1373/clinchem.2008.112797). The HT-J assay has been approved
for use in JD control programs in Australia and New Zealand.
PMID- 24352998
TI - Characterization of a novel melt curve by use of the Roche LightCycler HSV 1/2
analyte-specific reagent real-time PCR assay: frequencies of this novel (low)
melt curve and commonly encountered (intermediate) melt curves.
AB - We characterize a novel probe binding-site polymorphism detectable solely by melt
curve analysis using the Roche LightCycler HSV 1/2 analyte-specific reagent real
time PCR assay. The frequencies of this novel (47 degrees C) and previously
described intermediate (60 to 62 degrees C) melt curves were 0.016% and 4.9%,
respectively.
PMID- 24352997
TI - Spectrum of pneumococcal serotype 11A variants results from incomplete loss of
capsule O-acetylation.
AB - Streptococcus pneumoniae is a significant bacterial pathogen that expresses >90
capsule serotypes. Conventional serotyping methods assume that each serotype is a
genetically and antigenically distinct entity; however, recent investigations
have revealed pneumococcal isolates that cannot be unambiguously serotyped
because they share the properties of more than one serotype. Here, we employed a
novel serotyping method and NMR spectroscopy to examine clinical isolates sharing
properties of serotypes 11A and 11E. These ambiguous clinical isolates were
provisionally named 11A variant (11Av) isolates. Serotype 11A pneumococci
characteristically express capsule beta-galactose-6-O-acetylation (betaGal6OAc)
mediated by the capsule synthesis gene wcjE, while 11E strains contain loss-of
function mutations in wcjE and completely lack the expression of betaGal6OAc.
Although 11Av isolates also contained mutated wcjE alleles, 11Av clinical
isolates were composed of antigenically homogeneous bacteria expressing reduced
amounts of 11A-specific capsule antigen. NMR data confirmed reduced but
detectable amounts of betaGal6OAc on 11Av capsule polysaccharide. Furthermore,
the transformation of strains with wcjE alleles from 11Av strains was sufficient
to restore partial betaGal6OAc in an 11E background. We conclude that, instead of
being distinct entities, serotypes 11A and 11E represent two extremes of an
antigenic spectrum resulting from variable capsule O-acetylation secondary to
heterologous wcjE mutations. These findings challenge whether all clinically
relevant pneumococci can be definitively categorized into distinct serotypes.
PMID- 24352999
TI - Comparison of Illumigene, Simplexa, and AmpliVue Clostridium difficile molecular
assays for diagnosis of C. difficile infection.
AB - We compared the performance of the Simplexa Universal Direct (Focus Diagnostics)
and AmpliVue (Quidel Corporation) assays to that of the Illumigene assay
(Meridian Bioscience, Inc.) for the diagnosis of Clostridium difficile infection.
Two hundred deidentified remnant diarrheal stool specimens were tested by the
Simplexa, AmpliVue, and Illumigene methods. Specimens with discrepant results
among the three assays and a representative number of concordant specimens were
further evaluated by toxigenic culture. The sensitivity and specificity were 98
and 100% and 96 and 100% for the Simplexa Universal Direct and AmpliVue assays,
respectively. Both assays are easy to perform, with rapid turn-around-times,
supporting their utility in the clinical laboratory as routine diagnostic
platforms.
PMID- 24353001
TI - Automated versus manual sample inoculations in routine clinical microbiology: a
performance evaluation of the fully automated InoqulA instrument.
AB - The process of plate streaking has been automated to improve the culture
readings, isolation quality, and workflow of microbiology laboratories. However,
instruments have not been well evaluated under routine conditions. We aimed to
evaluate the performance of the fully automated InoqulA instrument (BD Kiestra
B.V., The Netherlands) in the automated seeding of liquid specimens and samples
collected using swabs with transport medium. We compared manual and automated
methods according to the (i) within-run reproducibility using Escherichia coli
calibrated suspensions, (ii) intersample contamination using a series of
alternating sterile broths and broths with >10(5) CFU/ml of either E. coli or
Proteus mirabilis, (iii) isolation quality with standardized mixed bacterial
suspensions of diverse complexity and a 4-category standardized scale (very poor,
poor, fair to good, or excellent), and (iv) agreement of the results obtained
from 244 clinical specimens. By involving 15 technicians in the latter part of
the comparative study, we estimated the variability in the culture quality at the
level of the laboratory team. The instrument produced satisfactory
reproducibility with no sample cross-contamination, and it performed better than
the manual method, with more colony types recovered and isolated (up to 11% and
17%, respectively). Finally, we showed that the instrument did not shorten the
seeding time over short periods of work compared to that for the manual method.
Altogether, the instrument improved the quality and standardization of the
isolation, thereby contributing to a better overall workflow, shortened the time
to results, and provided more accurate results for polymicrobial specimens.
PMID- 24353000
TI - Development of two antibody detection enzyme-linked immunosorbent assays for
serodiagnosis of human chronic fascioliasis.
AB - Coprological examination based on egg detection in stool samples is currently
used as the gold standard for the diagnosis of human fascioliasis. However, this
method is not effective during the acute phase of the disease and has poor
sensitivity during the chronic phase. Serodiagnosis has become an excellent
alternative to coprological examination in efforts to combat the effects of
fascioliasis on human and animal health. Two novel recombinant Fasciola hepatica
proteins, i.e., a ferritin (FhFtn-1) and a tegument-associated protein
(FhTP16.5), were used as antigens to develop in-house enzyme-linked immunosorbent
assay (ELISA) methods. The assays were optimized and validated using 152 serum
samples from humans with a known infection status, including healthy subjects,
patients with chronic fascioliasis, and patients with other parasitic diseases.
The FhFtn-1 ELISA was shown to be 96.6% sensitive and 95.7% specific; the
respective parameters for the FhTP16.5 ELISA were 91.4% and 92.4%. The
performances of the FhFtn-1 and FhTP16.5 ELISAs were compared with that of an
available commercial test (the DRG test) using a subset of serum samples. Our in
house tests were slightly more sensitive than the DRG test in detecting
antibodies against F. hepatica, but the differences were not statistically
significant. In conclusion, the present study provides evidence for the potential
of the FhFtn-1 and FhTP16.5 ELISAs as diagnostic tools for human fascioliasis, as
might be implemented in conjunction with standard assays for large-scale
screenings in areas where the disease is endemic and for the detection of
occasional cases in clinical laboratories.
PMID- 24353002
TI - Predicting extensively drug-resistant Mycobacterium tuberculosis phenotypes with
genetic mutations.
AB - Molecular diagnostic methods based on the detection of mutations conferring drug
resistance are promising technologies for rapidly detecting multidrug
/extensively drug-resistant tuberculosis (M/XDR TB), but large studies of
mutations as markers of resistance are rare. The Global Consortium for Drug
Resistant TB Diagnostics analyzed 417 Mycobacterium tuberculosis isolates from
multinational sites with a high prevalence of drug resistance to determine the
sensitivities and specificities of mutations associated with M/XDR TB to inform
the development of rapid diagnostic methods. We collected M/XDR TB isolates from
regions of high TB burden in India, Moldova, the Philippines, and South Africa.
The isolates underwent standardized phenotypic drug susceptibility testing (DST)
to isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin
(AMK), kanamycin (KAN), and capreomycin (CAP) using MGIT 960 and WHO-recommended
critical concentrations. Eight genes (katG, inhA, rpoB, gyrA, gyrB, rrs, eis, and
tlyA) were sequenced using Sanger sequencing. Three hundred seventy isolates were
INHr, 356 were RIFr, 292 were MOXr/OFXr, 230 were AMKr, 219 were CAPr, and 286
were KANr. Four single nucleotide polymorphisms (SNPs) in katG/inhA had a
combined sensitivity of 96% and specificities of 97 to 100% for the detection of
INHr. Eleven SNPs in rpoB had a combined sensitivity of 98% for RIFr. Eight SNPs
in gyrA codons 88 to 94 had sensitivities of 90% for MOXr/OFXr. The rrs 1401/1484
SNPs had 89 to 90% sensitivity for detecting AMKr/CAPr but 71% sensitivity for
KANr. Adding eis promoter SNPs increased the sensitivity to 93% for detecting
AMKr and to 91% for detecting KANr. Approximately 30 SNPs in six genes predicted
clinically relevant XDR-TB phenotypes with 90 to 98% sensitivity and almost 100%
specificity.
PMID- 24353003
TI - Development of a Luminex-based multiplex assay for detection of mutations
conferring resistance to Echinocandins in Candida glabrata.
AB - Echinocandins are the recommended treatment for invasive candidiasis due to
Candida glabrata. Resistance to echinocandins is known to be caused by
nonsynonymous mutations in the hot spot-1 (HS1) regions of the FKS1 and FKS2
genes, which encode a subunit of the beta-1,3-glucan synthase, the target of
echinocandins. Here, we describe the development of a microsphere-based assay
using Luminex MagPix technology to identify mutations in the FKS1 HS1 and FKS2
HS1 domains, which confer in vitro echinocandin resistance in C. glabrata
isolates. The assay is rapid and can be performed with high throughput. The assay
was validated using 102 isolates that had FKS1 HS1 and FKS2 HS1 domains
previously characterized by DNA sequencing. The assay was 100% concordant with
DNA sequencing results. The assay was then used for high-throughput screening of
1,032 C. glabrata surveillance isolates. Sixteen new isolates with mutations,
including a mutation that was new to our collection (del659F), were identified.
This assay provides a rapid and cost-effective way to screen C. glabrata isolates
for echinocandin resistance.
PMID- 24353004
TI - Impact of proficiency testing program for laboratories conducting early diagnosis
of HIV-1 infection in infants in low- to middle-income countries.
AB - A voluntary, cost-free external quality assessment (EQA) program established by
the U.S. Centers for Disease Control and Prevention (CDC) was implemented to
primarily monitor the performance of laboratories conducting HIV Early Infant
Diagnosis (EID) from dried blood spots (DBS) in low- to middle-income countries
since 2006. Ten blind DBS proficiency test (PT) specimens and 100 known HIV
positive and -negative DBS specimens (to be used as internal controls) were
shipped triannually to participating laboratories with reports for the PT
specimens due within 30 days. The participant's results and a summary of the
performance of all participating laboratories and each diagnostic method were
provided after each test cycle. Enrollment in the CDC PT program expanded
progressively from 17 laboratories from 11 countries in 2006 to include 136
laboratories from 41 countries at the end of 2012. Despite external pressures to
test and treat more children while expanding EID programs, mean PT test scores
significantly improved over time as demonstrated by the upward trend from mid
2006 to the end of 2012 (P=0.001) and the increase in the percentage of
laboratories scoring 100% (P=0.003). The mean test scores plateaued over the past
10 testing cycles, ranging between 98.2% and 99.7%, and discordant test results
still occur but at a rate of no higher than 2.6%. Analysis of these test results
suggests a positive impact of proficiency testing on the testing performance of
the participating laboratories, and a continuous training program and proficiency
testing participation may translate into laboratories improving their testing
accuracy.
PMID- 24353005
TI - The seventh pandemic Vibrio cholerae O1 El Tor isolate in China has undergone
genetic shifts.
AB - A total of 330 clinical Vibrio cholerae O1 serogroups from China dating between
1961 and 2010 were investigated. By phenotypic biotyping and genetic analysis,
during the seventh pandemic of V. cholerae O1 in China, the isolates of hybrid
biotype (mixed classical phenotypes) were present during the entire1961-2010
period, while El Tor genetic shifts appeared in 1992 and replaced the prototype
El Tor from 2002 to 2010.
PMID- 24353006
TI - PhyloFlu, a DNA microarray for determining the phylogenetic origin of influenza A
virus gene segments and the genomic fingerprint of viral strains.
AB - Recent evidence suggests that most influenza A virus gene segments can contribute
to the pathogenicity of the virus. In this regard, the hemagglutinin (HA) subtype
of the circulating strains has been closely surveyed, but the reassortment of
internal gene segments is usually not monitored as a potential source of an
increased pathogenicity. In this work, an oligonucleotide DNA microarray
(PhyloFlu) designed to determine the phylogenetic origins of the eight segments
of the influenza virus genome was constructed and validated. Clades were defined
for each segment and also for the 16 HA and 9 neuraminidase (NA) subtypes. Viral
genetic material was amplified by reverse transcription-PCR (RT-PCR) with primers
specific to the conserved 5' and 3' ends of the influenza A virus genes, followed
by PCR amplification with random primers and Cy3 labeling. The microarray
unambiguously determined the clades for all eight influenza virus genes in 74%
(28/38) of the samples. The microarray was validated with reference strains from
different animal origins, as well as from human, swine, and avian viruses from
field or clinical samples. In most cases, the phylogenetic clade of each segment
defined its animal host of origin. The genomic fingerprint deduced by the
combined information of the individual clades allowed for the determination of
the time and place that strains with the same genomic pattern were previously
reported. PhyloFlu is useful for characterizing and surveying the genetic
diversity and variation of animal viruses circulating in different environmental
niches and for obtaining a more detailed surveillance and follow up of
reassortant events that can potentially modify virus pathogenicity.
PMID- 24353007
TI - Gliomatosis cerebri type 1 with extensive involvement of the spinal cord and BRAF
V600E mutation.
AB - Gliomatosis cerebri (GC) is a rare neoplasm in which there is a diffuse cerebral
infiltration by malignant glial cells with relative conservation of the
underlying structures. A 67-year-old lady was admitted complaining of balance
problems, troubled breathing, stuttered speech, decreased mobility, progressive
ataxia and also some mild cognitive problems. MRI demonstrated ill defined T2
hyperintensity with mild mass effect mainly involving the brain stem and
cerebellar hemispheres, with minor signal abnormalities extending
supratentorially along the corticospinal tracts. The imaging appearances were
static over a year. No biopsy was performed. The patient received palliative care
and died 2 years after initial presentation. Macroscopic examination of the brain
showed an extensive firm white-grey lesion predominantly in the cerebellar white
matter, the brainstem, spreading to the full length of the spinal cord and
invading the sensory ganglia. Histology revealed an extensively infiltrating
diffuse glioma with small elongated fusiform nuclei. Diagnosis of GC type 1 was
made. Molecular genetic tests revealed BRAF V600E mutation, while no IDH1 & IDH2
mutations were found. GC should be taken into account in the differential
diagnoses mainly when there is rapid clinical deterioration without clear
evidence of radiological progression. Extensive spinal cord infiltration has been
reported only in 9% and BRAF V600E mutation was detected only in one case in GC
previously. Future clinical trials should address whether BRAF V600E mutant brain
tumour patients will benefit from BRAF V600E-directed targeted therapies.
PMID- 24353009
TI - Exposure to crystalline silica in abrasive blasting operations where silica and
non-silica abrasives are used.
AB - Exposure to respirable crystalline silica is a hazard common to many industries
in Alberta but particularly so in abrasive blasting. Alberta occupational health
and safety legislation requires the consideration of silica substitutes when
conducting abrasive blasting, where reasonably practicable. In this study,
exposure to crystalline silica during abrasive blasting was evaluated when both
silica and non-silica products were used. The crystalline silica content of non
silica abrasives was also measured. The facilities evaluated were preparing metal
products for the application of coatings, so the substrate should not have had a
significant contribution to worker exposure to crystalline silica. The
occupational sampling results indicate that two-thirds of the workers assessed
were potentially over-exposed to respirable crystalline silica. About one-third
of the measurements over the exposure limit were at the work sites using silica
substitutes at the time of the assessment. The use of the silica substitute, by
itself, did not appear to have a large effect on the mean airborne exposure
levels. There are a number of factors that may contribute to over-exposures,
including the isolation of the blasting area, housekeeping, and inappropriate use
of respiratory protective equipment. However, the non-silica abrasives themselves
also contain silica. Bulk analysis results for non-silica abrasives commercially
available in Alberta indicate that many contain crystalline silica above the
legislated disclosure limit of 0.1% weight of silica per weight of product (w/w)
and this information may not be accurately disclosed on the material safety data
sheet for the product. The employer may still have to evaluate the potential for
exposure to crystalline silica at their work site, even when silica substitutes
are used. Limited tests on recycled non-silica abrasive indicated that the silica
content had increased. Further study is required to evaluate the impact of
product recycling on crystalline silica content for non-silica abrasives.
Measurement of blaster exposure was challenging in this study as the blasters
evaluated conducted this task intermittently throughout the work shift,
frequently removing their blasting helmets. In spite of the challenges in
accurately measuring blaster exposure, the measurements were still, for the most
part, over the 8-h OEL. Further work is required to develop more effective
sampling strategies to evaluate blaster exposure over the full work shift when
task-based monitoring is not practical.
PMID- 24353011
TI - Targeted therapies in brain metastases.
AB - OPINION STATEMENT: Brain metastases are a major clinical problem in patients with
advanced breast cancer, lung cancer, melanoma, and renal cell carcinoma. Initial
treatment for patients with brain metastases typically includes radiotherapy,
either whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both.
Surgical resection is generally reserved for good prognosis patients with
limited/controlled extracranial metastases and a single brain lesion. Once
patients progress through upfront treatment, the treatment approach is quite
variable and there is no clearly defined standard-of-care. Over the past decade,
the role of systemic therapies and in particular, targeted therapies has been
increasingly explored in patients with brain metastases from solid tumors. For
example, lapatinib has been studied as monotherapy, and in combination with
capecitabine, in patients with HER2-positive breast cancer, and activity has been
observed in both the upfront and refractory settings. In patients with nonsmall
cell lung cancer (NSCLC), central nervous system (CNS) activity has been reported
with gefinitib and erlotinib. Finally, in melanoma, the B-raf inhibitors
vemurafenib and dabrafenib, and the immunomodulator, ipilumimab, have reported
CNS activity. Moving forward, the challenge will be to understand how to optimize
the activity of targeted agents in the CNS and how to best incorporate them into
the current treatment paradigms in order to improve outcomes for this patient
population.
PMID- 24353012
TI - Enantioselective copper-catalyzed decarboxylative propargylic alkylation of
propargyl beta-ketoesters with a chiral ketimine P,N,N-ligand.
AB - The first enantioselective copper-catalyzed decarboxylative propargylic
alkylation has been developed. Treatment of propargyl beta-ketoesters with a
catalyst, prepared in situ from [Cu(CH3 CN)4 BF4 ] and a newly developed chiral
tridentate ketimine P,N,N-ligand under mild reaction conditions, generates beta
ethynyl ketones in good yields and with high enantioselectivities without
requiring the pregeneration of ketone enolates. This new process provides facile
access to a range of chiral beta-ethynyl ketones in a highly enantioenriched
form.
PMID- 24353008
TI - Chronic obstructive pulmonary disease mortality and prevalence: the associations
with smoking and poverty--a BOLD analysis.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a commonly reported
cause of death and associated with smoking. However, COPD mortality is high in
poor countries with low smoking rates. Spirometric restriction predicts mortality
better than airflow obstruction, suggesting that the prevalence of restriction
could explain mortality rates attributed to COPD. We have studied associations
between mortality from COPD and low lung function, and between both lung function
and death rates and cigarette consumption and gross national income per capita
(GNI). METHODS: National COPD mortality rates were regressed against the
prevalence of airflow obstruction and spirometric restriction in 22 Burden of
Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking
prevalence. The prevalence of airflow obstruction and spirometric restriction in
the BOLD sites were regressed against GNI and mean pack years smoked. RESULTS:
National COPD mortality rates were more strongly associated with spirometric
restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90,
p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than
obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years:
men rs=0.28, p=0.23; women rs=0.22, p=0.33). Obstruction increased with mean pack
years smoked, but COPD mortality fell with increased cigarette consumption and
rose rapidly as GNI fell below US$15 000. Prevalence of restriction was not
associated with smoking but also increased rapidly as GNI fell below US$15 000.
CONCLUSIONS: Smoking remains the single most important cause of obstruction but a
high prevalence of restriction associated with poverty could explain the high
'COPD' mortality in poor countries.
PMID- 24353010
TI - Statistical performance of observational work sampling for assessment of
categorical exposure variables: a simulation approach illustrated using PATH
data.
AB - OBJECTIVES: Observational work sampling is often used in occupational studies to
assess categorical biomechanical exposures and occurrence of specific work tasks.
The statistical performance of data obtained by work sampling is, however, not
well understood, impeding informed measurement strategy design. The purpose of
this study was to develop a procedure for assessing the statistical properties of
work sampling strategies evaluating categorical exposure variables and to
illustrate the usefulness of this procedure to examine bias and precision of
exposure estimates from samples of different sizes. METHODS: From a parent data
set of observations on 10 construction workers performing a single operation, the
probabilities were determined for each worker of performing four component tasks
and working in four mutually exclusive trunk posture categories (neutral, mild
flexion, severe flexion, twisted). Using these probabilities, 5000 simulated data
sets were created via probability-based resampling for each of six sampling
strategies, ranging from 300 to 4500 observations. For each strategy, mean
exposure and exposure variability metrics were calculated at both the operation
level and task level and for each metric, bias and precision were assessed across
the 5000 simulations. RESULTS: Estimates of exposure variability were
substantially more uncertain at all sample sizes than estimates of mean exposures
and task proportions. Estimates at small sample sizes were also biased. With only
600 samples, proportions of the different tasks and of working with a neutral
trunk posture (the most common) were within 10% of the true target value in at
least 80% of all the simulated data sets; rarer exposures required at least 1500
samples. For most task-level mean exposure variables and for all operation-level
and task-level estimates of exposure variability, performance was low, even with
4500 samples. In general, the precision of mean exposure estimates did not depend
on the exposure variability between workers. CONCLUSIONS: The suggested
probability-based simulation approach proved to be versatile and generally
suitable for assessing bias and precision of data collection strategies using
work sampling to estimate categorical data. The approach can be used in both real
and hypothetical scenarios, in ergonomics, as well as in other areas of
occupational epidemiology and intervention research. The reported statistical
properties associated with sample size are likely widely relevant to studies
using work sampling to assess categorical variables.
PMID- 24353013
TI - Hedgehog signalling is dispensable in the proliferation of stem cells from human
exfoliated deciduous teeth.
AB - The hedgehog (Hh) signalling pathway is one of the key regulators in development
with a dual role in cell fate specification, proliferation, and survival on
different target cells. We have investigated the effect of recombinant sonic
hedgehog (r-SHH) on extracted multipotent stem cells from human exfoliated
deciduous teeth (SHED), which represent a potential stem cell population for
therapeutic applications. Cell proliferation and cycle assays shown that r-SHH
did not have a distinctive effect on cell cycle progression, nor did it increase
cell number over a wide range of concentrations. Quantitative polymerase chain
reaction (Q-PCR) also suggests that r-SHH treatment has no demonstrable influence
on expression of proliferative genes (CCNE1 and KI67); in contrast, the anti
proliferative gene (CDKN1A) is overexpressed in response to SHH. Our findings
have suggested the possibility that SHEDs demonstrate a different potential from
human bone marrow mesenchymal stem cells (h-BMSCs) and dorsal neural progenitor
in response to growth factors such as SHH.
PMID- 24353014
TI - Clusterin in Alzheimer's disease: a player in the biological behavior of amyloid
beta.
AB - Alzheimer's disease (AD) remains a major killer, and although its pathogenesis
varies, one dominant feature is an increase in the expression, formation, and
sedimentation of senile plaques of amyloid-beta (Abeta) peptides in the brain.
The chaperone protein clusterin has, since its first discovery at the end of the
20(th) century, been labeled as a cytoprotector. However, epigenetic studies
showing that clusterin is associated with the severity and risk of AD, especially
in the hippocampus, triggered studies to clarify its role in the pathogenesis of
AD. It is true that clusterin can inhibit the aggregation of Abeta and therefore
prevent further formation of senile plaques in the AD brain, yet it induces the
formation of soluble forms of Abeta which are toxic to neurons. Another
problematic finding is that clusterin is involved in a pathway through which
Abeta has neurodegenerative effects intracellularly. Although the role of
clusterin in the pathogenesis of AD is still not clear, this review specifically
discusses the interactions between clusterin and Abeta, to open up the
possibility of a potential therapeutic approach for treating AD.
PMID- 24353016
TI - Structure-based and fragment-based GPCR drug discovery.
AB - G protein-coupled receptors (GPCRs) are an important family of membrane proteins;
historically, drug discovery in this target class has been fruitful, with many of
the world's top-selling drugs being GPCR modulators. Until recently, the modern
techniques of structure- and fragment-based drug discovery had not been fully
applied to GPCRs, primarily because of the instability of these proteins when
isolated from their cell membrane environments. Recent advances in receptor
stabilisation have facilitated major advances in GPCR structural biology over the
past six years, with 21 new receptor targets successfully crystallised with one
or more ligands. The dramatic increase in GPCR structural information has yielded
an increased use of structure-based methods for hit identification and
progression, which are reviewed herein. Additionally, a number of fragment-based
drug discovery techniques have been validated for use with GPCRs in recent years;
these approaches and their use in hit identification are reviewed.
PMID- 24353015
TI - Activation of the Akt-mTOR pathway and receptor tyrosine kinase in patients with
solitary fibrous tumors.
AB - BACKGROUND: Solitary fibrous tumors (SFTs) are soft tissue tumors of intermediate
malignancy that rarely metastasize. Although unresectable SFTs are reported to
have a poor prognosis, to the authors' knowledge there is currently no effective
therapy. Molecular target therapy is a promising approach for patients with
unresectable tumors, but knowledge of the molecular biology of SFTs is currently
insufficient to support such therapy. The current study investigated the
activation of receptor tyrosine kinases (RTKs) and the Akt-mammalian target of
rapamycin (Akt-mTOR) pathway in SFTs as therapeutic targets. METHODS: The
phosphorylation statuses of Akt-mTOR pathway proteins (p-Akt, p-mTOR,
phosphorylated 4E-binding protein [p-4EBP1], and phosphorylated S6 ribosomal
protein [p-S6RP]) and RTKs (phosphorylated platelet-derived growth factor
receptor-alpha [p-PDGFRalpha], p-PDGFRbeta, p-c-met, and phosphorylated insulin
like growth factor-1 receptor-beta [p-IGF-1Rbeta]) were assessed by
immunohistochemistry in 66 samples of SFTs, and the data were compared with
clinicopathological and histopathological findings. The expression of
phosphorylated proteins was assessed by Western blot analysis in 6 frozen
samples. RESULTS: The immunohistochemical results were as follows: p-Akt, 56.0%
(nuclear and cytoplasmic staining); p-mTOR, 69.6% (nuclear and cytoplasmic
staining); p-4EBP1, 80.3% (nuclear and cytoplasmic staining); p-S6RP, 69.6%
(cytoplasmic staining); p-PDGFRalpha, 39.0% (cytoplasmic staining); p-PDGFRbeta,
52.0% (cytoplasmic staining); p-c-met, 37.8% (nuclear staining) and 19.6%
(cytoplasmic staining); and p-IGF-1Rbeta, 16.6% (nuclear staining).
Phosphorylation of the Akt-mTOR pathway proteins was correlated with one another
except for p-Akt with S6RP. p-PDGFRbeta and p-IGF-1Rbeta were correlated with p
Akt. Moreover, significant relationships were noted between disease-free survival
or overall survival and the presence of hypoglycemia, necrosis, cystic and myxoid
degeneration, and atypical findings. CONCLUSIONS: The Akt/mTOR pathway was
activated in approximately 50% of the cases of SFTs and was associated with RTKs,
which were phosphorylated at different rates. Thus, the Akt-mTOR pathway may be
involved in the tumorigenesis of SFTs.
PMID- 24353017
TI - The prevalence and economic impact of prescription opioid-related side effects
among patients with chronic noncancer pain.
AB - OBJECTIVES: To estimate the prevalence of opioid-related side effects among
patients with chronic noncancer pain (CNCP) who initiated opioids and compare
healthcare costs of patients with and without side effects using patient survey,
medical charts, and claims data. PATIENTS, PARTICIPANTS: Patients initiating
opioids, who were aged >=18 years, had >=1 pain diagnosis, and did not have
cancer, were identified through claims data and medical records from a Central
Massachusetts medical group practice and mailed surveys between October 2010 and
July 2012. MAIN OUTCOMES MEASURES: Prevalence of opioid-related side effects was
estimated from patient surveys, charts, and claims data within 90 days after
opioid initiation (study period). Study period healthcare costs were compared
between patients with and without side effects (self-reported problematic side
effects or side effects recorded in medical charts or claims). RESULTS: Among
patients with CNCP who initiated opioids and completed the survey (N = 167), the
average age was 53 years, and 62.9 percent were women. Based on the survey,
charts, and claims, 91.6 percent, 15.0 percent, and 19.2 percent of patients,
respectively, had >=1 opioid-related side effect. Overall, 59.3 percent of
patients reported having >=1 problematic side effect or side effect recorded in
charts or claims. In the analysis that controlled for baseline characteristics
and resource use, patients with versus without side effects had higher mean study
period healthcare costs ($3,347 vs $2,521, p = 0.049). CONCLUSIONS: Prevalence of
opioid-related side effects among patients with CNCP who initiated opioids was
substantially higher based on patient survey than from charts or claims. Opioid
related side effects were associated with significantly higher healthcare costs.
PMID- 24353018
TI - Switching from high doses of pure MU-opioid agonists to transdermal buprenorphine
in patients with cancer: a feasibility study.
AB - BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible
analgesic ceiling effect, feasibility of combination with other opioid agonists,
and the reversibility of side effects. Aim to evaluate: 1) if cancer patients
receiving high doses of pure agonists could obtain adequate pain relief after
switching to transdermal (TD) buprenorphine and 2) whether the numbers of
breakthrough pain episodes after switching increased and whether they could be
treated with the same doses of pure agonist as before switching. DESIGN: The
prospective open multicenter study included outpatients with moderate-to-severe
cancer pain satisfactorily controlled. SETTING: Patients were switched from the
usual pure agonist to TD buprenorphine and were titrated to a stable dose. The
assessments were: 1) daily self-assessment of pain intensity, numbers of rescue
medications, and pain interference with sleep; 2) brief pain inventory; 3) pain
relief and pain intensity; 4) quality of life; and 5) adverse events and
symptoms. RESULTS: Eighteen patients receiving 150-516 mg of morphine/day were
included. The buprenorphine dose at the end of the study varied between 52.5 and
140 MUg/h. No difference in pain before and after switching was shown. The level
of rescue doses was maintained. The patches were well tolerated. A significant
decrease in fatigue and an increase in global health status were seen after the
switch. CONCLUSION: It is feasible to switch cancer patients from high doses of
pure MU-opioid agonists to TD buprenorphine without eliciting any antagonist
effects, but the dose conversion factor is individual and the switching process
should be tailored for the individual patient.
PMID- 24353019
TI - Prolonged QT interval by methadone: relevance for daily practice? A prospective
study in patients with cancer and noncancer pain.
AB - INTRODUCTION: Increased methadone use in patients with pain has raised concerns
that the effect of methadone on the QT interval duration and the potential risk
of torsades de pointes (TdP) has been underestimated. Most studies on prolonged
QT intervals by methadone are performed in maintenance patients; however, doses
of methadone in pain treatment are much lower. Hardly any studies have
prospectively addressed QT interval prolongation by methadone in patients with
pain, and this study aims to address this literature gap. METHODS: In a period of
3 years, while 130 patients used methadone as pain treatment at a stable dose for
at least 1 week, 12-lead electrocardiograms (ECGs) were performed. Corrected QT
times, demographic features, methadone dose, duration of therapy, and relevant
comedication were documented. RESULTS: The findings included 50 percent of 130
patients, with a mean methadone dose of 18.2 mg/d, were potentially at risk for
TdP. Beyond this, 5 percent were at definite risk for TdP. No correlations were
found between QTc and gender, age, serum potassium or magnesium levels, methadone
dose, underlying disease, or comedication. CONCLUSION: The study found that in
our patients with pain, with relatively low doses of methadone, 5 percent had QTc
times >=500 ms and were thus at serious at risk for TdP. ECGs have to be made in
all patients with methadone therapy 1 week after introducing methadone (or after
dosage increases).
PMID- 24353021
TI - The misuse of prescription pain medication and borderline personality
symptomatology.
AB - OBJECTIVE: Despite the known high rates of substance misuse among individuals
with borderline personality disorder (BPD), little empirical data are available
regarding the explicit nature of such misuse with prescribed pain medications-the
focus of the present study. SETTING: A primary care outpatient setting, with
predominantly resident providers, in a midsized mid-western US city. PATIENTS:
Consecutive outpatients who currently or have previously been prescribed pain
medication (ie, lifetime pain medication exposure) (n = 185). MAIN OUTCOME
MEASURES: Relationships between BPD, according to two measures, and eight author
developed items reflecting prescription pain medication misuse. RESULTS: With the
exception of requesting a prescription for pain medication but not having pain
(n.s.), all other measures of prescription pain medication misuse were
statistically significantly associated with BPD symptoms. There were also some
statistically significant interactions between male gender and BPD symptoms in
the prediction of pain medication misuse (ie, mixing prescribed pain medications
with drugs to get high, using prescribed pain medication for recreational
purposes, and selling prescribed pain medications for money). CONCLUSIONS:
Individuals with BPD are at risk for misusing prescribed pain medications, and
this is especially evident regarding particular forms of misuse among men with
BPD symptomatology.
PMID- 24353020
TI - Effect of intraoral and subcutaneous morphine on dyspnea at rest in terminal
patients with primary lung cancer or lung metastases.
AB - BACKGROUND: Dyspnea is considered as one of the most frequent and distressing
symptoms in patients with advanced cancer, and systemic administration of
morphine has been reported to have beneficial effect on this complaint. AIM AND
DESIGN: The effect of red morphine drops (RMD) given orally and kept in the mouth
as long as possible before swallowing to alleviate dyspnea was compared to the
effect of morphine given subcutaneously (SCM) in a double-blind, double-dummy
trial. PARTICIPANTS: Twenty consecutive terminally ill patients with primary lung
cancer or lung metastases admitted to Sankt Lukas Hospice were included in the
study. All patients had dyspnea at rest, and they received either 1/12 of their
24-hour morphine dose as RMD or 60 percent of this dose as SCM. Perceived
breathlessness was evaluated on a Visual Analogue Scale (VAS) during a 60 minutes
observation time, and pulse rate, respiratory rate and oxygen saturation were
assessed as well. RESULTS: Compared to baseline both RMD and SCM showed a small,
but statistical significant effect on VAS (mean decrease of 1.1 [RMD] and 1.7
[SCM]) and pulse rate (mean decrease of 4 per minute [RMD] and 6 per minute
[SCM]), the effect being significantly larger after SCM. CONCLUSIONS: The study
confirms the beneficial effect of morphine on dyspnea in terminally ill patients,
and we conclude that RMD is an attractive alternative to injected morphine, when
self-administration is preferable.
PMID- 24353022
TI - Immediate-release tapentadol or oxycodone for treatment of acute postoperative
pain after elective arthroscopic shoulder surgery: a randomized, phase IIIb
study.
AB - OBJECTIVE: Arthroscopic shoulder surgery can result in substantial postoperative
pain. This study evaluated the efficacy and safety of tapentadol immediate
release (IR) or oxycodone IR in this setting for the treatment of acute pain.
DESIGN: Subjects received tapentadol IR 50 or 100 mg or oxycodone IR 5 or 10 mg
every 4-6 hours as needed for pain up to 7 days after arthroscopic shoulder
surgery. Twice daily, subjects recorded pain intensity from 0 (no pain) to 10
(pain as bad as you can imagine) and pain relief from 0 (none) to 5 (complete).
Final assessments included patient and clinician global impression of change and
subject satisfaction with treatment. The primary efficacy endpoint was the sum of
pain intensity differences (SPID) over 3 days. RESULTS: Of 378 subjects (192
tapentadol IR, 186 oxycodone IR) who took study medication, 312 (158 tapentadol
IR, 154 oxycodone IR) had pain intensity >=4 before the first dose and were
evaluated for efficacy. Mean SPID scores over 3 days were 32.1 and 41.1 in the
tapentadol IR and oxycodone IR groups, respectively (least-squares mean
difference [95% confidence interval], 9.0 [-18.9, 36.9]; p = 0.527). Secondary
analyses of pain intensity, pain relief, and subject satisfaction were similar
between groups. Subjects and clinicians reported significantly better global
impression of change for tapentadol IR. Adverse events were consistent with
established safety profiles for IR opioids. CONCLUSIONS: Tapentadol IR and
oxycodone IR had similar efficacy for pain after arthroscopic shoulder surgery,
but subjects and clinicians reported greater overall improvement with tapentadol
IR.
PMID- 24353023
TI - Pharmacokinetic evaluation of tapentadol extended-release tablets in healthy
subjects.
AB - OBJECTIVE: To evaluate serum pharmacokinetics of tapentadol administered to
healthy subjects as extended-release (ER) tablets. DESIGN: Seven single-dose
studies (five randomized, crossover, bioequivalence studies; a study in Japanese
men; and a randomized, crossover, effects-of-food study) and one repeated-dose
study. SETTING: Clinical research settings in the United States and The
Netherlands. PATIENTS OR PARTICIPANTS: Healthy males and females were enrolled
into seven studies; one study enrolled only Japanese males. INTERVENTIONS: In the
bioequivalence studies, subjects first received one polyethylene oxide- or
hypromellose-based tapentadol ER tablet (50, 100, 150, 200, or 250 mg; one dose
per study), then (after washout) the other formulation (matching dose). In all
other studies, subjects received polyethylene oxide-based tapentadol ER tablets.
In the repeated-dose study, subjects received one 250 mg tablet, then (after
washout) one 250 mg tablet every 12 hours (five doses). In the food-effect study,
subjects received one 250 mg tablet within 30 minutes after a high-fat meal or
after 10 hours of fasting. In the study in Japanese men, subjects received one
100 mg tablet. MAIN OUTCOME MEASURES: Maximum tapentadol concentrations (Cmax)
were typically observed 5 hours after dosing. Mean terminal half-life values
ranged from 4.4 to 5.9 hours. Tapentadol Cmax and AUC values increased
proportionally following single ER (polyethylene oxide-based tablets) doses of 50
to 250 mg. Trough tapentadol concentrations increased during repeat dosing until
reaching steady-state by the third dose. Serum Cmax and area under the
concentration-time curve (AUC) values at steady state were 1.6 and 1.9 times
higher relative to single-dose administration. Coadministration of the 250 mg
dose with a high-fat meal increased Cmax and AUC values by an average of < 17
percent. CONCLUSIONS: The pharmacokinetics of tapentadol ER are consistent after
repeated and single-dose administration. Tapentadol ER may be administered
without regard to food intake. No clinically significant differences were
observed in the pharmacokinetics of tapentadol between Japanese and Caucasian
subjects.
PMID- 24353024
TI - Loperamide: from antidiarrheal to analgesic.
AB - Loperamide, an antidiarrheal drug has been observed to produce analgesia in
animal models of pain. However, the exact mechanism underlying loperamide
analgesia needs further studies.
PMID- 24353025
TI - Merkel cell polyomavirus (MCPyV) strains in Japanese merkel cell carcinomas (MCC)
are distinct from Caucasian type MCPyVs: genetic variability and phylogeny of
MCPyV genomes obtained from Japanese MCPyV-infected MCCs.
AB - Most of merkel cell carcinomas (MCC), a rare, aggressive skin cancer with
neuroendocrine features, harbor merkel cell polyomavirus (MCPyV).
Seroepidemiological studies suggested high prevalence of MCPyV in the human
population. More than ten sequence data on MCPyV strains in Japan have been
available, whereas most sequence data were detected from patients living in
Europe or European ancestry. Analysis of nine almost complete and 19 partial
sequences from two oncogenes, small T antigen (ST) and large T antigen (LT)
genomes obtained from 32 Japanese MCPyV-infected MCC revealed that each Japanese
MCPyV-infected MCC harbored a specific MCPyV strain with some synonymous or,
silent mutations and stop codons or deletions, but functional domains of T
antigen had no amino acid changes. All stop codons were localized after
retinoblastoma protein-binding domain. These Japanese MCPyV strains were very
closely interrelated to themselves and a consensus sequence of Japanese strain
was generated. Phylogenetic analysis of our nine sequences and 70 other sequences
for ST and LT gene registered in GenBank indicated that Japanese or Asian MCPyV
strains formed distinct clades from Caucasian clade, and phylogenetic tree of our
nine and 75 other sequences for ST gene formed characteristic three clades and
showed that all Japanese or Asian strains were included in the dominant clade.
These suggested the possibility of geographically related genotypes of MCPyV. The
genomic characterization of MCPyV variants will provide an important database and
insights for illuminating their evolutional and biological differences.
PMID- 24353026
TI - Evidence of VP7 and VP4 intra-lineage diversification in G4P[8] Italian human
rotaviruses.
AB - Intragenotypic heterogeneity of co-circulating rotaviruses is remarkable.
Sequence and phylogenetic analyses of the rotavirus VP7 and VP4 genes were
performed on selected human G4P[8] strains identified in Parma, Northern Italy,
during 2004-2005 and 2008-2012. All the strains clustered into lineages Ic (VP7)
and P[8]-III (VP4) in different subclusters with a nucleotide sequence variation
up to 4 %. VP7 and VP4 amino acid sequences of the Italian rotaviruses showed
multiple changes with the corresponding reference strains as well as with vaccine
viruses in the neutralizing epitopes. There is concern that the progressive intra
lineage diversification in the VP7 and VP4 through the accumulation of point
mutations and amino acid differences between vaccine strains and currently
circulating rotaviruses could generate, over the years, vaccine-resistant
variants.
PMID- 24353028
TI - What is the role of the larynx in adult obstructive sleep apnea?
AB - OBJECTIVES/HYPOTHESIS: To examine the current body of literature supporting the
role of the larynx in adult obstructive sleep apnea (OSA). DATA SOURCES: PubMed.
METHODS: PubMed search using medical subject headings "larynx" and "obstructive
sleep apnea." Original articles in English related to adult patients were
initially included, and the bibliographies of pertinent articles were hand
searched for additional articles. RESULTS: A total of 17 articles were included
in the review in the following subgroups: neuromuscular role of larynx (n = 3),
anatomic contribution of larynx to OSA (n = 7), and special populations (n = 7).
The sensory component of the superior laryngeal nerve plays a critical role in
airway patency during sleep, and patients with OSA have increased endolaryngeal
sensory thresholds compared to controls. Primary epiglottic obstruction in the
hypopharynx represents 15% of patients with OSA unable to tolerate continuous
positive airway pressure. Head and neck cancer and multiple system atrophy are
two entities with high rates of OSA due in part to laryngeal abnormalities.
CONCLUSIONS: The endolarynx warrants consideration in the pathophysiology of OSA,
particularly as it relates to sensory dysfunction and epiglottic obstruction.
Patients with head and neck cancer of the laryngopharynx are at significant risk
of OSA. Further research is needed to better understand and heighten awareness of
the intimate role that the larynx may play in OSA.
PMID- 24353027
TI - Comparative analysis of endogenous plant pararetroviruses in cultivated and wild
Dahlia spp.
AB - Two distinct caulimoviruses, Dahlia mosaic virus (DMV) and Dahlia common mosaic
virus, and an endogenous plant pararetroviral sequence (DvEPRS) were reported in
Dahlia spp. DvEPRS, previously referred to as DMV-D10, was originally identified
in the US from the cultivated Dahlia variabilis, and has also been found in New
Zealand, Lithuania and Egypt, as well as in wild dahlia species growing in their
natural habitats in Mexico. Sequence analysis of three new EPRSs from cultivated
dahlias from Lithuania [D10-LT; 7,159 nucleotide level (nt)], New Zealand (D10
NZ, 7,156 nt), and the wild species, Dahlia rupicola, from Mexico (D10-DR, 7,133
nt) is reported in this study. The three EPRSs have the structure and
organization typical of a caulimovirus species and showed identities among
various open reading frames (ORFs) ranging between 71 and 97 % at the nt when
compared to those or the known DvEPRS from the US. Examination of a dataset of
seven full-length EPRSs obtained to date from cultivated and wild Dahlia spp.
provided clues into genetic diversity of these EPRSs from diverse sources of
dahlia. Phylogenetic analyses, mutation frequencies, potential recombination
events, selection, and fitness were evaluated as evolutionary evidences for
genetic variation. Assessment of all ORFs using phylogenomic and population
genetics approaches suggests a wide genetic diversity of EPRSs occurring in
dahlias. Phylogenetic analyses show that the EPRSs from various sources form one
clade indicating a lack of clustering by geographical origin. Grouping of various
EPRSs into two host taxa (cultivated vs. wild) shows little divergence with
respect to their origin. Population genetic parameters demonstrate negative
selection for all ORFs, with the reverse transcriptase region more variable than
other ORFs. Recombination events were found which provide evolutionary evidence
for genetic diversity among dahlia-associated EPRSs. This study contributes to an
increased understanding of molecular population genetics and evolutionary
pathways of these reverse transcribing viral elements.
PMID- 24353029
TI - Radiation burden from secondary doses to patients undergoing radiation therapy
with photons and light ions and radiation doses from imaging modalities.
AB - Ionising radiation is increasingly used for the treatment of cancer, being the
source of a considerable fraction of the medical irradiation to patients. With
the increasing success rate of cancer treatments and longer life expectancy of
the treated patients, the issue of secondary cancer incidence is of growing
concern, especially for paediatric patients who may live long after the treatment
and be more susceptible to carcinogenesis. Also, additional imaging procedures
like computed tomography, kilovoltage and megavoltage imaging and positron
emission tomography, alone or in conjunction with radiation therapy, may add to
the radiation burden associated with the risk of occurrence of secondary cancers.
This work has been based on literature studies and is focussed on the assessment
of secondary doses to healthy tissues that are delivered by the use of modern
radiation therapy and diagnostic imaging modalities in the clinical environment.
PMID- 24353030
TI - An internal radiation dosimetry computer program, IDAC 2.0, for estimation of
patient doses from radiopharmaceuticals.
AB - The internal dosimetry computer program internal dose assessment by computer
(IDAC) for calculations of absorbed doses to organs and tissues as well as
effective doses to patients from examinations with radiopharmaceuticals has been
developed. The new version, IDAC2.0, incorporates the International Commission on
Radiation Protection (ICRP)/ICRU computational adult male and female voxel
phantoms and decay data from the ICRP publication 107. Instead of only 25 source
and target regions, calculation can now be made with 63 source regions to 73
target regions. The major advantage of having the new phantom is that the
calculations of the effective doses can be made with the latest tissue weighting
factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract
(HAT) model for orally administrated activity and for excretion through the
gastrointestinal tract and effective doses have been recalculated for
radiopharmaceuticals that are orally administered. The results of the program are
consistent with published data using the same specific absorption fractions and
also compared with published data from the same computational phantoms but with
segmentation of organs leading to another set of specific absorption fractions.
The effective dose is recalculated for all the 34 radiopharmaceuticals that are
administered orally and has been published by the ICRP. Using the new HAT model,
new tissue weighting factors and the new adult computational voxel phantoms lead
to an average effective dose of half of its earlier estimated value. The
reduction mainly depends on electron transport simulations to walled organs and
the transition from the stylised phantom with unrealistic interorgan distances to
more realistic voxel phantoms.
PMID- 24353031
TI - Monte Carlo simulation-based feasibility study of a dose-area product meter built
into a collimator for diagnostic X-ray.
AB - According to the International Electro-technical Commission, manufacturers of X
ray equipment should indicate the number of radiation doses to which a patient
can be exposed. Dose-area product (DAP) meters are readily available devices that
provide dose indices. Collimators are the most commonly employed radiation beam
restrictors in X-ray equipment. DAP meters are attached to the lower surface of a
collimator. A DAP meter consists of a chamber and electronics. This separation
makes it difficult for operators to maintain the accuracy of a DAP meter.
Developing a comprehensive system that has a DAP meter in place of a mirror in
the collimator would be effective for measuring, recording the dose and
maintaining the quality of the DAP meter. This study was conducted through
experimental measurements and a simulation. A DAP meter built into a collimator
was found to be feasible when its reading was multiplied by a correction factor.
PMID- 24353032
TI - 25th anniversary article: scalable multiscale patterned structures inspired by
nature: the role of hierarchy.
AB - Multiscale, hierarchically patterned surfaces, such as lotus leaves, butterfly
wings, adhesion pads of gecko lizards are abundantly found in nature, where
microstructures are usually used to strengthen the mechanical stability while
nanostructures offer the main functionality, i.e., wettability, structural color,
or dry adhesion. To emulate such hierarchical structures in nature, multiscale,
multilevel patterning has been extensively utilized for the last few decades
towards various applications ranging from wetting control, structural colors, to
tissue scaffolds. In this review, we highlight recent advances in scalable
multiscale patterning to bring about improved functions that can even surpass
those found in nature, with particular focus on the analogy between natural and
synthetic architectures in terms of the role of different length scales. This
review is organized into four sections. First, the role and importance of
multiscale, hierarchical structures is described with four representative
examples. Second, recent achievements in multiscale patterning are introduced
with their strengths and weaknesses. Third, four application areas of wetting
control, dry adhesives, selectively filtrating membranes, and multiscale tissue
scaffolds are overviewed by stressing out how and why multiscale structures need
to be incorporated to carry out their performances. Finally, we present future
directions and challenges for scalable, multiscale patterned surfaces.
PMID- 24353033
TI - Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for
increasing the appropriateness of pharmacotherapy in the elderly.
AB - BACKGROUND: Multimorbidity and polypharmacy represent a major problem for elderly
patients; improvement of medication schemes is important and listing approaches
(e.g. Beers list) are considered to be potentially useful. OBJECTIVES: The aim of
this study was to perform expert consensus validation of the FORTA (Fit fOR The
Aged) List, a drug classification combining positive and negative labelling of
drugs chronically prescribed to elderly patients. METHODS: A two-round Delphi
procedure was conducted involving 20 experts, 17 geriatric internists and 3
geriatric psychiatrists from Germany and Austria, evaluating the labels assigned
to 190 substances or substance groups. These labels ranged from A
(indispensable), B (beneficial), C (questionable) to D (avoid), depending on the
state of evidence for safety, efficacy and overall age-appropriateness. The
experts were also requested to suggest additional substances and indication areas
for assessment and possible inclusion in the FORTA List. A weighted (corrected)
consensus coefficient was generated for each substance to reflect (1) agreement
with the original label, and (2) distribution among raters' labels. RESULTS: The
overall consensus for all items and raters was 92% (corrected). For 54/190 items
(28.4%), a unanimous response was achieved as to the original author-based FORTA
label choice. Twenty-four substances (12.6%) fell short of the consensus cutoff
and were re-evaluated in a second round. This yielded confirmation of 171/190, or
90%, of the original author-based FORTA labels. A total of 35 new substances were
also accepted for the FORTA List. Drugs used for dementia and dementia syndromes
provoked particular response heterogeneity. CONCLUSION: The FORTA List now
reflects a wider consensus among experts, increasing its validity for clinical
use. It represents a tool to improve the quality of drug prescription in older
patients by identifying both inappropriate and omitted drugs, and thus
overtreatment and undertreatment. The validation of FORTA's impact on clinical
endpoints has yielded promising preliminary results, to be corroborated in
ongoing larger trials.
PMID- 24353034
TI - Fake identities in social network research: to be disclosed?
PMID- 24353035
TI - Full functionalization of the imidazole scaffold by selective metalation and
sulfoxide/magnesium exchange.
AB - A simple, flexible, and straightforward method for the functionalization of all
the positions of the imidazole heterocycle through regioselective arylations,
allylations, acylations, and additions to aldehydes is disclosed. Starting from
the readily available key imidazole 1, highly functionalized imidazole
derivatives have been synthesized in a regioselective manner from directed
metalations and a sulfoxide/magnesium exchange. Moreover, the selective N3
alkylation followed by deprotection of N1 (trans-N-alkylation) allows the
regioselective N-alkylation of complex imidazoles.
PMID- 24353036
TI - (+)-Catechin attenuates activation of hepatic stellate cells.
AB - (+)-Catechin is a type of catechin present in large amounts in acai fruits and
cocoa seeds. Besides its antioxidant and anti-inflammatory activities, little is
known about its effects in the liver, especially during hepatic fibrosis. We
report here the effects of (+)-catechin on hepatic stellate cells. (+)-Catechin
induced quiescent phenotype in GRX cells, along with an increase in lipid
droplets. Proliferator-activated receptor gamma mRNA expression was upregulated,
whereas type I collagen mRNA expression was downregulated. Pro-inflammatory
cytokines were not influenced by (+)-catechin, whereas the levels of interleukin
10 were significantly increased. The data provide evidence that (+)-catechin can
reduce hepatic stellate cell activation.
PMID- 24353038
TI - Reply to A failure analysis of invasive breast cancer: most deaths from disease
occur in women not regularly screened.
PMID- 24353037
TI - Antiplatelet therapy: targeting the TxA2 pathway.
AB - The thromboxane (Tx) A2 pathway is a major contributor to the amplification of
the initial platelet activation process. TxA2 mediates its effect through the
thromboxane prostanoid (TP) receptor that is expressed not only in platelets, but
also in endothelial cells, macrophages, and monocytes, and thus contributes to
the development of atherosclerotic lesions. The TxA2 pathway is therefore a major
target in the treatment of cardiovascular disease. Aspirin-the most widely used
antiplatelet drug-is very effective at inhibiting platelet-derived TxA2
synthesis. However, aspirin's effects can be overcome by several other soluble
agonists such as isoprostanes, which are aspirin-insensitive ligands of the TP
receptor that are preferentially produced in diabetes mellitus. Other drugs, with
either inhibitory effects on Tx synthase or antagonist effects on TP, have been
developed with the hope of providing a better, more complete inhibition of the
TxA2 pathway.
PMID- 24353039
TI - Characterization of a novel cold-active esterase isolated from swamp sediment
metagenome.
AB - A functional screen of a metagenomic library from "Upo" swamp sediment in Korea
identified a gene EstL28, the product of which displayed lipolytic properties on
a tributyrin-supplemented medium. The EstL28 sequence encodes a 290 amino acid
protein (designated as EstL28), with a predicted molecular weight of 31.3 kDa.
The encoded EstL28 protein exhibited the highest sequence similarity (45 %) to a
hydrolase found in Streptococcus sanguinis. Phylogenetic analysis indicated that
EstL28 belongs to a currently uncharacterized family of esterases. Within the
conserved alpha/beta-hydrolase 6 domain, the EstL28 retains the catalytic triad
Ser103-Asp248-His268 that is typical of esterases. The Ser103 residue in the
catalytic triad is located in the consensus pentapeptide motif GXSXG. The
purified EstL28 enzyme worked optimally at 35 degrees C and pH 8.5 and remained
stable at temperatures lower than 20 degrees C. The catalytic activity of EstL28
was maximal with p-nitrophenyl butyrate, indicating that it was an esterase. This
enzyme also exhibited stable activity in the presence of methanol, ethanol,
isopropanol, and dimethyl sulfoxide. Therefore, the level of stability in organic
solvents and cold temperature suggests that EstL28 has potential for many
biotechnological applications.
PMID- 24353040
TI - Phenazine carboxylic acid production and rhizome protective effect of endophytic
Pseudomonas aeruginosa isolated from Zingiber officinale.
AB - Ginger (Zingiber officinale) is cultivated commercially in most parts of the
world especially in India for its culinary and medicinal applications. One of the
major challenges that limit the yield of ginger is rhizome rot disease caused by
organisms including Pythium myriotylum. A feasible ecofriendly method is yet to
be devised to prevent the plant from this threatening disease. Recent studies on
plant microbiome show the possibility of having endophytic organisms with plant
protective characteristics associated with the plants. Because of the uniquely
evolved underground nature of the ginger rhizome and its peculiar survival in
soil for a long time, many interesting endophytic microbes with plant protective
characters can be well expected from it. In the current study, previously
isolated endophytic Pseudomonas aeruginosa from ginger was investigated in detail
for its effect on Pythium myriotylum. The rhizome protective effect of the
organism was also studied by co-inoculation studies, which confirmed that
Pseudomonas aeruginosa has very potent inhibitory effect on Pythium myriotylum.
On further studies, the active antifungal compound was identified as phenazine 1
carboxylic acid.
PMID- 24353042
TI - Photocurrent enhancement in diketopyrrolopyrrole solar cells by manipulating
dipolar anchoring terminals on alkyl-chain spacers.
AB - We chose DPP-BDT-DPP {DPP=diketopyrrolopyrrole, BDT=4,8-di-[2-(2-ethylhexyl)
thienyl]benzo[1,2-b:4,5-b']dithiophene} as a model backbone and varied the
anchoring groups [?C5 H11 , ?COOCH3 , and ?SiCH3 (OSiCH3 )2 ] terminated on the N
substituted alkyl-chain spacer of the DPP units to study the effect of anchoring
terminals on the morphology of blend film and on the device performances of bulk
heterojunction solar cells. By replacing the nonpolar ?C5 H11 anchoring terminal
with the polar ?COOCH3 anchoring terminal leads to an enhancement in the short
circuit current density (Jsc ) (4.62 vs. 9.32 mA cm(-2) ), whereas the value of
Jsc sharply decreases to 0.45 mA cm(-2) if the ?C5 H11 anchoring terminal is
replaced by a ?SiCH3 (OSiCH3 )2 group. The changes in Jsc are associated with
changes in the pi-pi stacking distance (3.39->3.34 A vs. 3.39->3.45 A) and the
phase size (50->20 nm vs. 50->>250 nm) through alteration of the anchoring group
from ?C5 H11 to ?COOCH3 versus from ?C5 H11 to ?SiCH3 (OSiCH3 )2 . Interestingly,
the anchoring terminals bring about drastic changes in molecular orientations,
which result in different out-of-plane hole transport. This is the first time
this effect has been systemically demonstrated to improve photocurrent generation
by manipulating the dipolar anchoring groups terminated on the alkyl-chain
spacer.
PMID- 24353041
TI - Isolation of amylolytic, xylanolytic, and cellulolytic microorganisms extracted
from the gut of the termite Reticulitermes santonensis by means of a micro
aerobic atmosphere.
AB - The aim of this work was to isolate enzyme-producing microorganisms from the
tract of the termite Reticulitermes santonensis. The microorganisms were
extracted from the guts and anaerobic (CO2 or CO2/H2) and micro-aerobic
atmospheres were used to stimulate growth. Three different strategies were tried
out. First, the sample was spread on Petri dishes containing solid media with
carboxymethylcellulose, microcrystalline cellulose or cellobiose. This technique
allowed us to isolate two bacteria: Streptomyces sp. strain ABGxAviA1 and
Pseudomonas sp. strain ABGxCellA. The second strategy consisted in inoculating a
specific liquid medium containing carboxymethylcellulose, microcrystalline
cellulose, or cellobiose. The samples were then spread on Petri dishes with the
same specific medium containing carboxymethylcellulose, microcrystalline
cellulose, or cellobiose. This led to the isolation of the mold Aspergillus sp.
strain ABGxAviA2. Finally, the third strategy consisted in heating the first
culture and spreading samples on agar plates containing rich medium. This led to
the isolation of the bacterium Bacillus subtilis strain ABGx. All those steps
were achieved in controlled atmospheres. The four enzyme-producing strains which
were isolated were obtained by using a micro-aerobic atmosphere. Later, enzymatic
assays were performed on the four strains. Streptomyces sp. strain ABGxAviA1 was
found to produce only amylase, while Pseudomonas sp. strain ABGxCellA was found
to produce beta-glucosidase as well. Aspergillus sp. strain ABGxAviA2 showed beta
glucosidase, amylase, cellulase, and xylanase activities. Finally, B. subtilis
strain ABGx produced xylanase and amylase.
PMID- 24353043
TI - Reversible high-capacity Si nanocomposite anodes for lithium-ion batteries
enabled by molecular layer deposition.
AB - The molecular-layer deposition of a flexible coating onto Si electrodes produces
high-capacity Si nanocomposite anodes. Using a reaction cascade based on
inorganic trimethylaluminum and organic glycerol precursors, conventional nano-Si
electrodes undergo surface modifications, resulting in anodes that can be cycled
over 100 times with capacities of nearly 900 mA h g(-1) and Coulombic
efficiencies in excess of 99%.
PMID- 24353044
TI - Aberrant behaviors in a primary care-based cohort of patients with chronic pain
identified as misusing prescription opioids.
AB - OBJECTIVE: To assess aberrant drug-related behaviors (ADRBs) in patients
discharged from a community primary care practice for opioid misuse and treating
physician's ability to identify predictive aberrant behaviors. DESIGN:
Retrospective chart review of patients with chronic noncancer pain (CNCP)
identified by their treating physician as misusing opioid analgesics, and
patients with similar characteristics who had not been identified as misusing
opioids. A survey of attending and resident physicians from these clinics on
their knowledge of ADRBs was also collected. SETTING: Community primary care
clinic. PATIENTS, PARTICIPANTS: Thirty-three patients with CNCP identified by
their treating physician as misusing prescription opioid analgesics, and 33
patients randomly selected from the same clinic setting, with similar
characteristics who had not been identified as misusing opioids. Twenty-four
attending physicians and 42 resident physicians were surveyed on their training
and knowledge of predictive aberrant behaviors. RESULTS: More identified misusers
than nonmisusers reported positive history of substance abuse (p=0.001), tobacco
use (p=0.011), taking multiple doses of prescribed opioids together (0.024),
multiple complaints of pain requiring opioid treatment (p=0.006), and multiple
phone calls to the clinic requesting opioid medications (p=0.027). Logistic
regression on continuous variables revealed that only the number of phone calls
to the clinic regarding opioids in the last 12 months achieved significance
(p=0.028). CONCLUSIONS: Previously postulated and novel ADRBs suggestive of
opioid misuse were identified in a community primary care setting. Differences in
resident and attending physician's ability to identify key predictive ADRBs and
lack of training in pain or addiction underscores the need for changes in medical
school and residency programs.
PMID- 24353045
TI - Patterns of care and side effects for patients prescribed methadone for treatment
of chronic pain.
AB - OBJECTIVES: This manuscript evaluates physician monitoring practices and
incidence of cardiac side effects following initiation of methadone for treatment
of chronic pain as compared to patients who began treatment for chronic pain with
morphine sustained release (SR). DESIGN: We retrospectively reviewed medical
record data on all new initiations of methadone and compared results of physician
monitoring practices to patients with new initiations of morphine SR. A
standardized chart tool was used to capture clinical data. Data related to health
service utilization and clinical diagnoses were obtained from the VA clinical
information system. SETTING: A single VA Medical Center in the Pacific Northwest.
PATIENTS: Chronic pain patients prescribed methadone (n=92) or morphine (n=90) in
the calendar year 2008. RESULTS: There was no difference between patients
prescribed methadone versus patients prescribed morphine SR in the likelihood of
receiving an electrocardiogram (ECG) prior to initiating medication (53 percent
versus 54 percent) or in the year after opioid initiation (37 percent versus 40
percent). The two groups also did not differ in rates of developing prolonged
rate-corrected (QTc) intervals (>450 ms) (11 percent versus 17 percent). Seventy
two percent of all patients discontinued their long-acting opioid regimens before
90 days due to adverse effects or insufficient pain relief. CONCLUSION: Despite
recommendations for standardized assessment and cardiac risk monitoring, few
patients prescribed methadone received an ECG, and this occurred at a rate that
did not differ from patients prescribed morphine SR. Patients discontinued both
medications at high rates. Further research is needed to evaluate the clinical
significance of QTc prolongation in patients treated with methadone.
PMID- 24353046
TI - The characteristics of postoperative fentanyl effect-site concentration during
intravenous fentanyl analgesia after posterior lumbar spine fusion.
AB - OBJECTIVE: To examine the characteristics of postoperative fentanyl effect-site
concentrations during intravenous analgesia in patients requiring or not
requiring a fentanyl bolus and in patients with or without postoperative nausea
and vomiting (PONV). DESIGN: Retrospective observational study. SETTING:
University-affiliated general hospital. PATIENTS: Sixty patients who underwent
posterior lumbar spine fusion. MAIN OUTCOME MEASURES: The authors simulated the
fentanyl effect-site concentration for 48 postoperative hours and compared it
between patients who did and did not require a fentanyl bolus and between
patients who did and did not experience PONV. RESULTS: At the end of anesthesia,
the fentanyl effect-site concentration was similar between 37 (61.7 percent)
patients requiring and 23 (38.3 percent) patients not requiring a postoperative
fentanyl bolus (p=0.97). Within the first 12 postoperative hours, the
concentration decreased in both groups (p < 0.01). The fentanyl effect-site
concentration was higher in patients requiring a postoperative fentanyl bolus
(within 12 hours, 1.4 +/- 0.32 ng/mL vs 0.89 +/- 0.35 ng/mL; between 12 and 48
hours, 0.94 +/- 0.19 ng/mL vs 0.57 +/- 0.09 ng/mL) (p < 0.05). PONV occurred in
22 (36.6 percent) patients, but more so in women (68.2 percent; p < 0.01); PONV
was similar between patients requiring and not requiring a fentanyl bolus
(p=0.78). Between the 12th and 48th postoperative hours, fentanyl effect-site
concentrations were higher in patients with PONV (0.61 +/- 0.10 ng/mL vs 0.57 +/-
0.10 ng/mL, p=0.03). CONCLUSIONS: Patients needing a postoperative fentanyl bolus
require a higher fentanyl effect-site concentration possibly because of
individual variations, and PONV depends on the postoperative fentanyl effect-site
concentration.
PMID- 24353047
TI - A pooled analysis of patient-specific factors and efficacy and tolerability of
tapentadol extended release treatment for moderate to severe chronic pain.
AB - OBJECTIVE: To evaluate via retrospective analysis the efficacy and tolerability
of tapentadol extended release (ER; 100-250 mg bid) based on patient-specific
factors, including baseline pain intensity, prior opioid experience, gender, and
body mass index (BMI). DESIGN: Data were pooled from three randomized, double
blind phase III studies of similar design that evaluated the efficacy and
tolerability of tapentadol ER for the management of moderate to severe, chronic
osteoarthritis knee pain (NCT00421928, NCT00486811) or low back pain
(NCT00449176). SETTING: In the original trials, patients were recruited at
primary, secondary, and tertiary care centers, institutional settings, and
private practices in North America, Europe, Australia, and New Zealand. PATIENTS:
Data were analyzed separately for groups of patients divided by baseline pain
intensity, prior opioid experience, gender, and BMI. INTERVENTIONS: Patients
received twice-daily placebo, tapentadol ER (100-250 mg), or oxycodone HCl
controlled release (CR; 20-50 mg) for a 3-week titration and 12-week maintenance
period. MAIN OUTCOME MEASURES: Changes from baseline in average pain intensity
(11-point numerical rating scale) at week 12 of the maintenance period and for
the overall maintenance period. RESULTS: Efficacy and tolerability were evaluated
in 2,968 and 2,974 patients, respectively. The efficacy of tapentadol ER was
shown in subpopulations divided by baseline pain intensity, prior opioid
experience, gender, and BMI. Tapentadol ER was also shown to be well tolerated
and associated with better gastrointestinal tolerability than oxycodone CR in the
evaluated subpopulations (divided by prior opioid experience and gender).
CONCLUSIONS: Results suggest that tapentadol ER (100-250 mg bid) provides similar
pain relief and tolerability, regardless of baseline pain intensity, prior opioid
experience, gender, or BMI.
PMID- 24353048
TI - Opioid therapy in children and adolescents: a physician's guide to risk
assessment, monitoring, and mitigation of abuse.
AB - After conducting a thorough literature search of adolescent opioid use from 1990
until present, it became readily apparent that the last decade has witnessed an
increase in the number of opioid-related drug overdoses and deaths in the
adolescent population, analogous to the epidemic in the adult population. Most of
these cases have resulted from prescription medication misuse. Practitioners who
use controlled substances to treat pain in pediatric and adolescent patients want
to limit harm by carefully assessing their patients' risk of abuse and diversion.
In this article, the authors present current knowledge and recommendations for
the mitigation of aberrant prescription drug use in the pediatric population.
PMID- 24353049
TI - Survey of naloxone legal status in opioid overdose prevention and treatment.
AB - OBJECTIVE: To survey the federal and state-by-state legal status for prescribing,
dispensing, and administering naloxone injection. DESIGN: The survey was a review
of legislation, which encompassed analyzing current and proposed laws regarding
naloxone's role in opioid overdose prevention and treatment. MAIN OUTCOME
MEASURE(S): The primary study outcome was to evaluate the legal aspects of
current naloxone overdose prevention and treatment. Aspects of the legislation
studied included Food and Drug Administration (FDA) regulatory status, prescriber
authorization, prescription requirements, defining the patient, authority to
administer naloxone, status of lay person administration, and provisions for Good
Samaritan protections from criminal and civil liability. RESULTS: To date, 10
states have legislation implementing opioid overdose prevention programs
including naloxone. Several states with high opioid overdose burdens are in the
legislative process. Reasons for hesitation to initiate such programs include
fear of liability, a proxy endorsement for drug abuse, and apprehension of
increasing drug usage. CONCLUSIONS: A number of state legislatures have passed
legislation permitting lay administration of naloxone to individuals in an
attempt to revive a person with an apparent opioid overdose. These emerging state
policy initiatives parallel similar laws and regulations governing lay person
epinephrine administration for anaphylaxis and applying automated electric
defibrillators for sudden cardiac arrest. Public health initiatives increasing
access to naloxone will likely continue in states with high opioid overdose
burdens. FDA approval of a new needle-free naloxone delivery system would
facilitate greater public access.
PMID- 24353050
TI - A review of the use of ketamine in pain management.
AB - Ketamine is a noncompetitive antagonist of N-methyl-d-aspartate receptor. It has
been widely used in anesthesia and pain management. Ketamine has been
administered via the intravenous, intramuscular, subcutaneous, oral, rectal,
topical, intranasal, sublingual, epidural, and caudal routes. Ketamine improves
postoperative and posttrauma pain scores and reduces opioid consumption. It has
special indication for patients with opioid tolerance, acute hyperalgesia, and
neuropathic pain. It also has a role in the management of chronic pain including
both cancer and noncancer pain. Recreational use of ketamine is increasing as
well through different routes of administration like inhalation, smoking, or
intravenous injection. Long-time exposure to ketamine, especially in the abusers,
may lead to serious side effects. This review is trying to define the role of
ketamine in pain management.
PMID- 24353052
TI - CORR Insights(r): Developing a pathway for high-value, patient-centered total
joint arthroplasty.
PMID- 24353051
TI - Do activity levels increase after total hip and knee arthroplasty?
AB - BACKGROUND: People with osteoarthritis (OA) often are physically inactive.
Surgical treatment including total hip arthroplasty or total knee arthroplasty
can substantially improve pain, physical function, and quality of life. However,
their impact on physical activity levels is less clear. QUESTIONS/PURPOSES: We
used accelerometers to measure levels of physical activity pre- and (6 months)
postarthroplasty and to examine the proportion of people meeting the American
Physical Activity Guidelines. METHODS: Sixty-three people with hip or knee OA
awaiting arthroplasty were recruited from a major metropolitan hospital. Physical
activity was measured using accelerometry before, and 6 months after, surgery.
The ActiGraph GT1M (ActiGraph LLC, Fort Walton Beach, FL, USA) was used in this
study and is a uniaxial accelerometer contained within a small activity monitor
designed to measure human movement through changes in acceleration, which can
then be used to estimate physical activity over time. Questionnaires were used to
assess patient-reported changes in pain, function, quality of life, and physical
activity. Complete data sets (including valid physical activity data) for both
time points were obtained for 44 participants (70%). At baseline before
arthroplasty, the activity level of patients was, on average, sedentary for 82%
of the time over a 24-hour period (based on accelerometry) and self-rated as
"sometimes participates in mild activities such as walking, limited shopping, and
housework" according to the UCLA activity scale. RESULTS: There was no change in
objectively measured physical activity after arthroplasty. The majority of
participants were sedentary, both before and after arthroplasty, and did not meet
the American Physical Activity Guidelines recommended to promote health. This was
despite significant improvements in self-reported measures of pain, function,
quality of life, and physical activity after arthroplasty. CONCLUSIONS: Despite
patient-reported improvements in pain, function, and physical activity after
arthroplasty, objectively measured improvements in physical activity may not
occur. Clinicians should incorporate strategies for improving physical activity
into their management of patients after hip and knee arthroplasty to maximize
health status. Future research is needed to explore the factors that impact
physical activity levels in people after arthroplasty. LEVEL OF EVIDENCE: Level
IV, therapeutic study. See Guidelines for Authors for a complete description of
levels of evidence.
PMID- 24353054
TI - Evaluation of patient satisfaction with diabetes management provided by clinical
pharmacists in the patient-centered medical home.
AB - STUDY OBJECTIVE: The patient-centered medical home (PCMH) model is a
multidisciplinary, team-based approach to healthcare that focuses on actively
involving the patient in clinical decision making. Multiple studies have
demonstrated improved clinical outcomes from utilizing clinical pharmacists in
the primary care setting, particularly in management of diabetes. No study has
evaluated patient satisfaction with pharmacist in the PCMH model. Our objective
was to evaluate patient satisfaction of care received in pharmacist-managed
primary care clinics among patients with diabetes mellitus within the PCMH.
DESIGN: This study was a single-center, cross-sectional analysis of patients who
were seen by a clinical pharmacy specialist (CPS). SETTING: The setting for this
study was eight outpatient primary care clinics within a Veterans Affairs
healthcare system where diabetes management services were provided by eight CPSs.
PATIENTS: A total of 1,468 patients with a hemoglobin A1c >7.0 % who were seen in
clinic by a CPS at the primary care clinics between 1 October 2008 and 1 April
2012 were mailed the Modified Diabetes Disease State Management Questionnaire
(DDSM-QM). The DDSM-QM was a 15-item questionnaire that assessed overall patient
satisfaction with pharmacist care, as well as patient satisfaction within three
major domains: 'service,' 'self-management,' and 'knowledge'. MEASUREMENTS AND
MAIN RESULTS: A response rate of 42.7 % was attained, with 627 patients
consenting to participate by completing and returning the self-administered
questionnaire. The mean overall satisfaction score was 90.6 +/- 10.6 % (mean +/-
standard deviation). Mean percentage scores within the 'service,' 'knowledge,'
and 'self-management' domains were 92.0 +/- 10.8, 89.7 +/- 11.3, and 89.2 +/-
12.0 %, respectively. CONCLUSION: Patients with diabetes seen by a CPS within the
PCMH model were very satisfied with the care they received overall.
PMID- 24353053
TI - Asymmetry in semicircular canal diameters may account for circling behavior in
EphB-deficient mice.
AB - OBJECTIVES/HYPOTHESIS: Determine if differences in right and left semicircular
size account for phenotypic behavior, indicating vestibulopathy in EphB deficient
mice. STUDY DESIGN: The diameters of the superior semicircular canals (SCC) were
measured. The differences in the right and left superior SCC diameters were
analyzed in homozygous EphB2 and EphB3 double knockout mice known to have head
bobbing and circling behavior. Results were compared to similar analysis in wild
type controls that displayed no signs of vestibulopathy. METHODS: Axial frozen
sections through the superior (SCC) were analyzed by light microscopy; and the
diameters of the left and right canals were measured in MUm for both EphB2 and
EphB3 double knockout mice, as well as in wild type control mice. The differences
in diameter between the left and right superior SCC was determined for each
animal. RESULTS: Overall, the EphB2 and EphB3 double knockout mice had smaller
superior SCC diameters compared to wild type (109.0+/-21.4 MUm vs. 185.0+/-5.2
MUm (P<0.0001). The mean difference in left and right diameter of the superior
SCC of EphB2/EphB3 double knockout mice was 29.0+/-8.7 MUm; in wild-type controls
this difference was 6.0+/-5.1 MUm (P=0.002). In addition, the direction of
circling appeared to be independent of the laterality of the smaller (or larger)
superior SCC. CONCLUSION: Mice deficient in EphB2/EphB3 signaling have smaller
superior SCC and asymmetry in lumen sizes between the left and right sides. The
laterality of the larger versus smaller is not correlated with the direction of
circling behavior. LEVEL OF EVIDENCE: N/A.
PMID- 24353055
TI - New light on an old story: perovskites go solar.
PMID- 24353056
TI - Cyclo(D-Tyr-D-Phe): a new antibacterial, anticancer, and antioxidant cyclic
dipeptide from Bacillus sp. N strain associated with a rhabditid entomopathogenic
nematode.
AB - A new microbial cyclic dipeptide (diketopiperazine), cyclo(D-Tyr-D-Phe) was
isolated for the first time from the ethyl acetate extract of fermented modified
nutrient broth of Bacillus sp. N strain associated with rhabditid
Entomopathogenic nematode. Antibacterial activity of the compound was determined
by minimum inhibitory concentration and agar disc diffusion method against
medically important bacteria and the compound recorded significant antibacterial
against test bacteria. Highest activity was recorded against Staphylococcus
epidermis (1 ug/ml) followed by Proteus mirabilis (2 ug/ml). The activity of
cyclo(D-Tyr-D-Phe) against S. epidermis is better than chloramphenicol, the
standard antibiotics. Cyclo(D-Tyr-D-Phe) recorded significant antitumor activity
against A549 cells (IC50 value: 10 MUM) and this compound recorded no
cytotoxicity against factor signaling normal fibroblast cells up to 100 MUM.
Cyclo(D-Tyr-D-Phe) induced significant morphological changes and DNA
fragmentation associated with apoptosis in A549 cells. Acridine orange/ethidium
bromide stained cells indicated apoptosis induction by cyclo(D-Tyr-D-Phe). Flow
cytometry analysis showed that the cyclo(D-Tyr-D-Phe) did not induce cell cycle
arrest. Effector molecule of apoptosis such as caspase-3 was found activated in
treated cells, suggesting apoptosis as the main mode of cell death. Antioxidant
activity was evaluated by free radical scavenging and reducing power activity,
and the compound recorded significant antioxidant activity. The free radical
scavenging activity of cyclo(D-Tyr-D-Phe) is almost equal to that of butylated
hydroxyanisole, the standard antioxidant agent. We also compared the biological
activity of natural cyclo(D-Tyr-D-Phe) with synthetic cyclo(D-Tyr-D-Phe) and
cyclo(L-Tyr-L-Phe). Natural and synthetic cyclo(D-Tyr-D-Phe) recorded similar
pattern of activity. Although synthetic cyclo(L-Tyr-L-Phe) recorded lower
activity. But in the case of reducing power activity, synthetic cyclo(L-Tyr-L
Phe) recorded significant activity than natural and synthetic cyclo(D-Tyr-D-Phe).
The results of the present study reveals that cyclo(D-Tyr-D-Phe) is more
bioactive than cyclo(L-Tyr-L-Phe). To the best of our knowledge, this is the
first time that cyclo(D-Tyr-D-Phe) has been isolated from microbial natural
source and also the antibacterial, anticancer, and antioxidant activity of
cyclo(D-Tyr-D-Phe) is also reported for the first time.
PMID- 24353057
TI - PTK7 modulates Wnt signaling activity via LRP6.
AB - Protein tyrosine kinase 7 (PTK7) is a transmembrane protein expressed in the
developing Xenopus neural plate. PTK7 regulates vertebrate planar cell polarity
(PCP), controlling mesodermal and neural convergent-extension (CE) cell
movements, neural crest migration and neural tube closure in vertebrate embryos.
Besides CE phenotypes, we now show that PTK7 protein knockdown also inhibits
Wnt/beta-catenin activity. Canonical Wnt signaling caudalizes the neural plate
via direct transcriptional activation of the meis3 TALE-class homeobox gene,
which subsequently induces neural CE. PTK7 controls meis3 gene expression to
specify posterior tissue and downstream PCP activity. Furthermore, PTK7 morphants
phenocopy embryos depleted for Wnt3a, LRP6 and Meis3 proteins. PTK7 protein
depletion inhibits embryonic Wnt/beta-catenin signaling by strongly reducing LRP6
protein levels. LRP6 protein positively modulates Wnt/beta-catenin, but
negatively modulates Wnt/PCP activities. The maintenance of high LRP6 protein
levels by PTK7 triggers PCP inhibition. PTK7 and LRP6 proteins physically
interact, suggesting that PTK7 stabilization of LRP6 protein reciprocally
regulates both canonical and noncanonical Wnt activities in the embryo. We
suggest a novel role for PTK7 protein as a modulator of LRP6 that negatively
regulates Wnt/PCP activity.
PMID- 24353058
TI - Notch signaling is required for the formation of mesangial cells from a stromal
mesenchyme precursor during kidney development.
AB - Mesangial cells are specialized pericyte/smooth muscle cells that surround and
constrain the vascular network within the glomerulus of the kidney. They are
derived from the stromal mesenchyme, a progenitor population distinct from
nephron stem cells. Whether mesangial cells have a distinct origin from vascular
smooth muscle cells (VSMCs) and the pathways that govern their specification are
unknown. Here we show that Notch signaling in stromal progenitors is essential
for mesangial cell formation but is dispensable for the smooth muscle and
interstitial cell lineages. Deletion of RBPjk, the common DNA-binding partner of
all active Notch receptors, with Foxd1(tgCre) results in glomerular aneurysm and
perinatal death from kidney failure. This defect occurs early in glomerular
development as stromal-derived, desmin-positive cells fail to coalesce near
forming nephrons and thus do not invade the vascular cleft of the S-shaped body.
This is in contrast to other mutants in which the loss of the mesangium was due
to migration defects, and suggests that loss of Notch signaling results in a
failure to specify this population from the stroma. Interestingly, Pdgfrb
positive VSMCs do not enter the vascular cleft and cannot rescue the mesangial
deficiency. Notch1 and Notch2 act redundantly through gamma-secretase and RBPjk
in this process, as individual mutants have mesangial cells at birth. Together,
these data demonstrate a unique origin of mesangial cells and demonstrate a
novel, redundant function for Notch receptors in mesangial cell specification,
proliferation or survival during kidney development.
PMID- 24353059
TI - Crim1 maintains retinal vascular stability during development by regulating
endothelial cell Vegfa autocrine signaling.
AB - Angiogenesis defines the process in which new vessels grow from existing vessels.
Using the mouse retina as a model system, we show that cysteine-rich motor neuron
1 (Crim1), a type I transmembrane protein, is highly expressed in angiogenic
endothelial cells. Conditional deletion of the Crim1 gene in vascular endothelial
cells (VECs) causes delayed vessel expansion and reduced vessel density. Based on
known Vegfa binding by Crim1 and Crim1 expression in retinal vasculature, where
angiogenesis is known to be Vegfa dependent, we tested the hypothesis that Crim1
is involved in the regulation of Vegfa signaling. Consistent with this
hypothesis, we showed that VEC-specific conditional compound heterozygotes for
Crim1 and Vegfa exhibit a phenotype that is more severe than each single
heterozygote and indistinguishable from that of the conditional homozygotes. We
further showed that human CRIM1 knockdown in cultured VECs results in diminished
phosphorylation of VEGFR2, but only when VECs are required to rely on an
autocrine source of VEGFA. The effect of CRIM1 knockdown on reducing VEGFR2
phosphorylation was enhanced when VEGFA was also knocked down. Finally, an anti
VEGFA antibody did not enhance the effect of CRIM1 knockdown in reducing VEGFR2
phosphorylation caused by autocrine signaling, but VEGFR2 phosphorylation was
completely suppressed by SU5416, a small-molecule VEGFR2 kinase inhibitor. These
data are consistent with a model in which Crim1 enhances the autocrine signaling
activity of Vegfa in VECs at least in part via Vegfr2.
PMID- 24353060
TI - Postsynaptic glutamate receptors regulate local BMP signaling at the Drosophila
neuromuscular junction.
AB - Effective communication between pre- and postsynaptic compartments is required
for proper synapse development and function. At the Drosophila neuromuscular
junction (NMJ), a retrograde BMP signal functions to promote synapse growth,
stability and homeostasis and coordinates the growth of synaptic structures.
Retrograde BMP signaling triggers accumulation of the pathway effector pMad in
motoneuron nuclei and at synaptic termini. Nuclear pMad, in conjunction with
transcription factors, modulates the expression of target genes and instructs
synaptic growth; a role for synaptic pMad remains to be determined. Here, we
report that pMad signals are selectively lost at NMJ synapses with reduced
postsynaptic sensitivities. Despite this loss of synaptic pMad, nuclear pMad
persisted in motoneuron nuclei, and expression of BMP target genes was
unaffected, indicating a specific impairment in pMad production/maintenance at
synaptic termini. During development, synaptic pMad accumulation followed the
arrival and clustering of ionotropic glutamate receptors (iGluRs) at NMJ
synapses. Synaptic pMad was lost at NMJ synapses developing at suboptimal levels
of iGluRs and Neto, an auxiliary subunit required for functional iGluRs. Genetic
manipulations of non-essential iGluR subunits revealed that synaptic pMad signals
specifically correlated with the postsynaptic type-A glutamate receptors.
Altering type-A receptor activities via protein kinase A (PKA) revealed that
synaptic pMad depends on the activity and not the net levels of postsynaptic type
A receptors. Thus, synaptic pMad functions as a local sensor for NMJ synapse
activity and has the potential to coordinate synaptic activity with a BMP
retrograde signal required for synapse growth and homeostasis.
PMID- 24353063
TI - Tissue-specific and ubiquitous gene knockouts by TALEN electroporation provide
new approaches to investigating gene function in Ciona.
AB - Custom designed nucleases can simplify gene targeting experiments and have the
potential to allow these techniques to be performed in a wide range of organisms.
Transcriptional activator-like effector nucleases (TALENs) are starting to
fulfill this potential with the advantages of low cost and fast construction
times. Here, we report that TALENs are highly effective at inducing mutations in
specific genomic loci in the ascidian chordate Ciona intestinalis. In Ciona there
are well-established methods to introduce exogenous DNA by electroporation, and
we show that this method can be used to introduce constructs that can express
TALENs ubiquitously or in specific tissues. Our current protocols enable the
rapid analysis of hundreds of TALEN-induced mutants. TALEN electroporations
result in a high rate of mutations. These mutations can result in gene knockouts
that recapitulate previously described functions of Fgf3 and Hox12. We show that
TALENs can work efficiently to cause tissue-specific knockouts and demonstrate
this by knocking out Hox12 in the epidermis and Fgf3 in neural tissues. We also
use tissue-specific knockouts to reveal a new function of Fgf3 during ascidian
larval metamorphosis.
PMID- 24353061
TI - The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in
distinct cholinergic and serotonergic neuron types.
AB - Transcription factors that drive neuron type-specific terminal differentiation
programs in the developing nervous system are often expressed in several distinct
neuronal cell types, but to what extent they have similar or distinct activities
in individual neuronal cell types is generally not well explored. We investigate
this problem using, as a starting point, the C. elegans LIM homeodomain
transcription factor ttx-3, which acts as a terminal selector to drive the
terminal differentiation program of the cholinergic AIY interneuron class. Using
a panel of different terminal differentiation markers, including neurotransmitter
synthesizing enzymes, neurotransmitter receptors and neuropeptides, we show that
ttx-3 also controls the terminal differentiation program of two additional,
distinct neuron types, namely the cholinergic AIA interneurons and the
serotonergic NSM neurons. We show that the type of differentiation program that
is controlled by ttx-3 in different neuron types is specified by a distinct set
of collaborating transcription factors. One of the collaborating transcription
factors is the POU homeobox gene unc-86, which collaborates with ttx-3 to
determine the identity of the serotonergic NSM neurons. unc-86 in turn operates
independently of ttx-3 in the anterior ganglion where it collaborates with the
ARID-type transcription factor cfi-1 to determine the cholinergic identity of the
IL2 sensory and URA motor neurons. In conclusion, transcription factors operate
as terminal selectors in distinct combinations in different neuron types,
defining neuron type-specific identity features.
PMID- 24353062
TI - Differential activation of natriuretic peptide receptors modulates cardiomyocyte
proliferation during development.
AB - Organ development is a highly regulated process involving the coordinated
proliferation and differentiation of diverse cellular populations. The pathways
regulating cell proliferation and their effects on organ growth are complex and
for many organs incompletely understood. In all vertebrate species, the cardiac
natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the
developing heart. However, their role during cardiogenesis is not defined. Using
the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the
natriuretic peptide signaling network during myocardial development. We observed
that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase
linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant
during early cardiovascular development. In addition, we demonstrate that low
levels of the natriuretic peptides preferentially activate Npr3, a receptor with
Gi activator sequences, and increase cardiomyocyte proliferation through
inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic
peptides reduce cardiomyocyte proliferation through activation of the particulate
guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and
activation of protein kinase G. These data link the cardiac natriuretic peptides
in a complex hierarchy modulating cardiomyocyte numbers during development
through opposing effects on cardiomyocyte proliferation mediated through distinct
cyclic nucleotide signaling pathways.
PMID- 24353065
TI - Hexagonal bipyramidal [Ta(2)B(6)](-/0) clusters: B(6) rings as structural motifs.
AB - It has been a long-sought goal in cluster science to discover stable atomic
clusters as building blocks for cluster-assembled nanomaterials, as exemplified
by the fullerenes and their subsequent bulk syntheses.1, 2 Clusters have also
been considered as models to understand bulk properties, providing a bridge
between molecular and solid-state chemistry.3 Because of its electron deficiency,
boron is an interesting element with unusual polymorphism. While bulk boron is
known to be dominated by the three-dimensional (3D) B12 icosahedral motifs,4 new
forms of elemental boron are continuing to be discovered.5 In contrast to the 3D
cages commonly found in bulk boron, in the gas phase two-dimensional (2D) boron
clusters are prevalent.6-8 The unusual planar boron clusters have been suggested
as potential new bulking blocks or ligands in chemistry.6a Herein we report a
joint experimental and theoretical study on the [Ta2 B6 ](-) and [Ta2 B6 ]
clusters. We found that the most stable structures of both the neutral and anion
are D6h bipyramidal, similar to the recently discovered MB6 M structural motif in
the Ti7 Rh4 Ir2 B8 solid compound.9.
PMID- 24353064
TI - Fgf10-positive cells represent a progenitor cell population during lung
development and postnatally.
AB - The lung mesenchyme consists of a widely heterogeneous population of cells that
play crucial roles during development and homeostasis after birth. These cells
belong to myogenic, adipogenic, chondrogenic, neuronal and other lineages. Yet,
no clear hierarchy for these lineages has been established. We have previously
generated a novel Fgf10(iCre) knock-in mouse line that allows lineage tracing of
Fgf10-positive cells during development and postnatally. Using these mice, we
hereby demonstrate the presence of two waves of Fgf10 expression during embryonic
lung development: the first wave, comprising Fgf10-positive cells residing in the
submesothelial mesenchyme at early pseudoglandular stage (as well as their
descendants); and the second wave, comprising Fgf10-positive cells from late
pseudoglandular stage (as well as their descendants). Our lineage-tracing data
reveal that the first wave contributes to the formation of parabronchial and
vascular smooth muscle cells as well as lipofibroblasts at later developmental
stages, whereas the second wave does not give rise to smooth muscle cells but to
lipofibroblasts as well as an Nkx2.1(-) E-Cad(-) Epcam(+) Pro-Spc(+) lineage that
requires further in-depth analysis. During alveologenesis, Fgf10-positive cells
give rise to lipofibroblasts rather than alveolar myofibroblasts, and during
adult life, a subpopulation of Fgf10-expressing cells represents a pool of
resident mesenchymal stromal (stem) cells (MSCs) (Cd45(-) Cd31(-) Sca-1(+)).
Taken together, we show for the first time that Fgf10-expressing cells represent
a pool of mesenchymal progenitors in the embryonic and postnatal lung. Our
findings suggest that Fgf10-positive cells could be useful for developing stem
cell-based therapies for treating interstitial lung diseases.
PMID- 24353066
TI - Quality of life in head and neck cancer patients: impact of HPV and primary
treatment modality.
AB - OBJECTIVES/HYPOTHESIS: To determine posttreatment quality of life (QOL) in head
and neck cancer patients, stratifying by human papillomavirus (HPV)/p16 status
and primary treatment modality. STUDY DESIGN: Retrospective study. METHODS: One
hundred and seventy-seven patients (N=177) with head and neck squamous cell
carcinoma and known HPV/p16 status were included. All patients completed at least
one baseline or posttreatment University of Washington QOL survey. QOL scores
were averaged and compared across patients, stratifying by HPV/p16 status and
primary treatment modality (surgical vs. nonsurgical). In the analysis, p16 was
used as a surrogate marker for HPV. RESULTS: Of the 177 patients, 80 (45.2%) were
p16-positive and 49.7% of subsites were oropharyngeal. Nearly 60% (105/177) of
patients underwent primary surgery, 26.7% (28/105) of patients with transoral
robotic or laser techniques. The remainder 40.7% of patients underwent primary
radiation and/or chemotherapy. Overall, QOL scores were better for p16-positive
patients compared to p16-negative patients at baseline (P=0.008), at 6 months
posttreatment (P=0.034), and at greater than 1 year posttreatment (P=0.013). P16
positive patients had better QOL scores in speech (P=0.0009), chewing (P=0.0004),
and swallowing (P=0.021) after 1 year posttreatment compared to p16-negative
patients. Primary treatment modality did not affect overall QOL or any of the 12
QOL categories in p16-positive patients at any time point. At over 1 year
posttreatment, QOL was at or above baseline in both p16-positive treatment
groups. CONCLUSION: The p16-positive patients had better baseline and
posttreatment overall QOL compared to p16-negative patients. The overall and
category specific QOL scores for p16-positive patients were not affected by
primary treatment modality. LEVEL OF EVIDENCE: 4.
PMID- 24353068
TI - Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical
treatment of patients with indeterminate thyroid nodules: a prospective case
series of 960 patients.
PMID- 24353069
TI - An important side reaction using the thiol, 3,6-dioxa-1,8-octanedithiol (DODT),
in 9-fluorenylmethoxycarbonyl-based solid phase peptide synthesis.
AB - A considerable quantity of an alkylation by-product is observed when using 3,6
dioxa-1,8-octanedithiol as a scavenger during acidic release of peptides
containing the thioether amino acid methionine from the solid support. Adjustment
of the cleavage conditions by replacement of 3,6-dioxa-1,8-octanedithiol with
ethane dithiol or by using methionine sulfoxide as an alternative to methionine
resulted in no such impurity. The by-product was detectable by liquid
chromatography and mass spectrometry and characterised by NMR spectroscopy of an
isolated model peptide. It could be effectively removed in a separate post
cleavage step by treatment with dilute aqueous acid at 37 degrees C.
PMID- 24353070
TI - Flexible supercapacitor made of carbon nanotube yarn with internal pores.
AB - Electrochemical deposition of MnO2 onto carbon nanotube (CNT) yarn gives a high
performance, flexible yarn supercapacitor. The hybrid yarn's blended structure,
resulting from trapping of MnO2 in its internal pores, effectively enlarges
electrochemical area and reduces charge diffusion length. Accordingly, the yarn
supercapacitor exhibits high values of capacitance, energy density, and average
power density. Applications in wearable electronics can be envisaged.
PMID- 24353071
TI - Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing
cholangitis in Japan.
AB - BACKGROUND: We previously conducted nationwide surveys for primary sclerosing
cholangitis (PSC) in Japan, and demonstrated several characteristic features of
Japanese PSC patients, yet patients with IgG4-related sclerosing cholangitis
(IgG4-SC) might be misdiagnosed as PSC. Since the clinical diagnostic criteria of
IgG4-SC were established in 2012, we again conducted a nationwide survey to
investigate the characteristics of PSC and IgG4-SC lacking pancreatic
involvement. METHODS: The design was a questionnaire-based, multi-center
retrospective study. The enrolled subjects were patients with PSC and IgG4-SC
without pancreatic involvement diagnosed after 2005. RESULTS: We enrolled 197 PSC
and 43 IgG4-SC patients without pancreatic lesions. The male dominance was
significantly evident in IgG4-SC (P = 0.006). In patients with PSC, two peaks in
age distribution were clearly observed. IgG4-SC was not detected in any patient
younger than 45 years of age. At presentation, serum albumin and IgM were
significantly higher in PSC, while serum IgG and IgG4 were significantly elevated
in IgG4-SC. Inflammatory bowel disease (IBD) was detected in only 68/197 PSC
patients (34%). The prognosis of IgG4-SC was considerably better than that of
PSC. CONCLUSION: We confirmed several interesting clinical details of PSC in
Japanese patients: two peaks in the age distribution and lower prevalence of IBD.
PMID- 24353073
TI - Estimation of portal uptake function in the venous congestive area after hemi
hepatectomy: postoperative contrast-enhanced magnetic resonance imaging and
intraoperative indocyanine green-fluorescence imaging.
PMID- 24353074
TI - Reply to Norihiro Kokudo et al. Regional liver function is not "zero" in the
congestive area after hepatectomy with middle hepatic vein resection.
PMID- 24353075
TI - Pre-eruptive intracoronal dentine radiolucencies in the permanent dentition of
Jordanian children.
AB - PURPOSE: To determine the prevalence of pre-eruptive intracoronal dentine
radiolucencies (PEIR) and subject factors or dental conditions associated with
PEIR from orthopantograms (OPGs) in unerupted permanent teeth of children.
METHODS: OPGs were evaluated for 1,571 subjects (807 males, 764 females) with
mean age (8.72 +/- 2.5) years. Unerupted permanent teeth prior to emergence into
the oral cavity were assessed. The Chi square test was used to determine
statistical differences between the group showing and the group not showing the
defect with regards to sex, stage of dental development, presence of
developmental anomalies, and condition of primary predecessor teeth. RESULTS:
Prevalence was (8.1%) by subject and (0.62%) by teeth. All subjects showed only
one affected tooth per subject with no significant gender differences. The
highest prevalence was in mandibular first premolars (3.02%). Most defects were
noted in the mixed dentition stage (89.06%), mainly in the mandible (79.7%) as
single lesions at a mesial location intracoronally, and a size of less than one
third of dentine thickness in (50%). Among all variables examined, PEIR defects
were significantly associated with mixed dentition stage (p = 0.000) and
decayed/filled primary predecessor teeth (p = 0.028). CONCLUSIONS: PEIR defects
occur at a significant prevalence rate in unerupted teeth. Increased awareness
and careful radiographic examination of unerupted teeth may improve early
detection and treatment of PEIR defects in children.
PMID- 24353076
TI - Amelogenesis imperfecta associated with dental follicular-like hamartomas and
generalised gingival enlargement.
AB - BACKGROUND: Amelogenesis imperfecta (AI) is an inherited disorder characterised
by generalised defects of dental enamel, but has been associated with other
dental and medical conditions. It affects the appearance and structure of teeth,
both in the primary and secondary dentition. AI in the presence of dental
follicular hamartomas and gingival hyperplasia is rare and the management
presents several challenges to the clinician. CASE REPORT: This article describes
a case of a girl who presented to the paediatric department at the age of 7 years
complaining of discomfort when eating and that she was unhappy with the
appearance of her anterior teeth. The patient was born in the UK but she and her
family were African and of Kenyan origin. She was otherwise fit and well.
Investigations included clinical, radiographic and pathological examination as
well as cone beam computed tomography imaging and X-ray Microtomography of
extracted primary teeth. A diagnosis of AI in the presence of dental follicular
hamartomas and generalised gingival hyperplasia was made, which had resulted in
the delayed eruption of permanent teeth and an associated anterior open bite.
There was no family history of dental defects. TREATMENT: Initial treatment
included preventative advice and the application of preformed metal crowns on all
primary molars. Extraction of all remaining primary incisors was carried out
followed by gingivectomy around the maxillary permanent incisors, mandibular
central incisors and maxillary left second primary molar. Composite resin
reconstruction of all permanent incisors and mandibular primary canines was
complicated by the poor quality of enamel. Orthodontic extrusion of the anterior
incisors was carried out to improve surface area for bonding with some success. A
multidisciplinary team managed this case and decided that no surgical
intervention of the dental follicular hamartomas was warranted. FOLLOW-UP: The
patient coped well with treatment and attended for regular review over an 8-year
period. She was reviewed at 6 monthly intervals clinically by a paediatric
dentist and radiographs were taken as required to monitor the hamartomas,
maintain the restorations and monitor her dental development. She was also seen
on the multidisciplinary clinic once a year. CONCLUSION: This is the first case
of its kind to be reported in the UK and the 8th worldwide. While this condition
is rare, it is important that paediatric dentists are made aware of it.
PMID- 24353077
TI - A failure analysis of invasive breast cancer: most deaths from disease occur in
women not regularly screened.
PMID- 24353078
TI - Interdental brushing for the prevention and control of periodontal diseases and
dental caries in adults.
AB - BACKGROUND: Effective oral hygiene is a crucial factor in maintaining good oral
health, which is associated with overall health and health-related quality of
life. Dental floss has been used for many years in conjunction with toothbrushing
for removing dental plaque in between teeth, however, interdental brushes have
been developed which many people find easier to use than floss, providing there
is sufficient space between the teeth. OBJECTIVES: To evaluate the effects of
interdental brushing in addition to toothbrushing, as compared with toothbrushing
alone or toothbrushing and flossing for the prevention and control of periodontal
diseases, dental plaque and dental caries. SEARCH METHODS: We searched the
following electronic databases: the Cochrane Oral Health Group's Trials Register
(to 7 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library 2013, Issue 2), MEDLINE via OVID (1946 to 7 March 2013),
EMBASE via OVID (1980 to 7 March 2013), CINAHL via EBSCO (1980 to 7 March 2013),
LILACS via BIREME (1982 to 7 March 2013), ZETOC Conference Proceedings (1980 to 7
March 2013) and Web of Science Conference Proceedings (1990 to 7 March 2013). We
searched the US National Institutes of Health Trials Register
(http://clinicaltrials.gov) and the metaRegister of Controlled Trials
(http://www.controlled-trials.com/mrct/) for ongoing trials to 7 March 2013. No
restrictions were placed on the language or date of publication when searching
the electronic databases. SELECTION CRITERIA: We included randomised controlled
trials (including split-mouth design, cross-over and cluster-randomised trials)
of dentate adult patients. The interventions were a combination of toothbrushing
and any interdental brushing procedure compared with toothbrushing only or
toothbrushing and flossing. DATA COLLECTION AND ANALYSIS: At least two review
authors assessed each of the included studies to confirm eligibility, assessed
risk of bias and extracted data using a piloted data extraction form. We
calculated standardised mean difference (SMD) and 95% confidence interval (CI)
for continuous outcomes where different scales were used to assess an outcome. We
attempted to extract data on adverse effects of interventions. Where data were
missing or unclear we attempted to contact study authors to obtain further
information. MAIN RESULTS: There were seven studies (total 354 participants
analysed) included in this review. We assessed one study as being low, three
studies as being high and three studies as being at unclear risk of bias. Studies
only reported the clinical outcome gingivitis and plaque data, with no studies
providing data on many of the outcomes: periodontitis, caries, halitosis and
quality of life. Three studies reported that no adverse events were observed or
reported during the study. Two other studies provided some data on adverse events
but we were unable to pool the data due to lack of detail. Two studies did not
report whether adverse events occurred. Interdental brushing in addition to
toothbrushing, as compared with toothbrushing alone Only one high risk of bias
study (62 participants in analysis) looked at this comparison and there was very
low-quality evidence for a reduction in gingivitis (0 to 4 scale, mean in
control): mean difference (MD) 0.53 (95% CI 0.23 to 0.83) and plaque (0 to 5
scale): MD 0.95 (95% CI 0.56 to 1.34) at one month, favouring of use of
interdental brushes. This represents a 34% reduction in gingivitis and a 32%
reduction in plaque. Interdental brushing in addition to toothbrushing, as
compared with toothbrushing and flossing Seven studies provided data showing a
reduction in gingivitis in favour of interdental brushing at one month: SMD -0.53
(95% CI -0.81 to -0.24, seven studies, 326 participants, low-quality evidence).
This translates to a 52% reduction in gingivitis (Eastman Bleeding Index).
Although a high effect size in the same direction was observed at three months
(SMD -1.98, 95% CI -5.42 to 1.47, two studies, 107 participants, very low
quality), the confidence interval was wide and did not exclude the possibility of
no difference. There was insufficient evidence to claim a benefit for either
interdental brushing or flossing for reducing plaque (SMD at one month 0.10, 95%
CI -0.13 to 0.33, seven studies, 326 participants, low-quality evidence) and
insufficient evidence at three months (SMD -2.14, 95% CI -5.25 to 0.97, two
studies, 107 participants very low-quality evidence). AUTHORS' CONCLUSIONS: Only
one study looked at whether toothbrushing with interdental brushing was better
than toothbrushing alone, and there was very low-quality evidence for a reduction
in gingivitis and plaque at one month. There is also low-quality evidence from
seven studies that interdental brushing reduces gingivitis when compared with
flossing, but these results were only found at one month. There was insufficient
evidence to determine whether interdental brushing reduced or increased levels of
plaque when compared to flossing.
PMID- 24353081
TI - Direct route to 1,3-diketones by palladium-catalyzed carbonylative coupling of
aryl halides with acetylacetone.
PMID- 24353082
TI - A sulfonic-azobenzene-grafted silica amphiphilic material: a versatile stationary
phase for mixed-mode chromatography.
AB - A novel sulfonic-azobenzene-functionalized amphiphilic silica material was
synthesized through the preparation of a new sulfonic azobenzene monomer and its
grafting on mercaptopropyl-modified silica by a surface-initiated radical chain
transfer reaction. The synthesis was confirmed by infrared spectra, elemental
analysis, and thermogravimetric analysis. This new material was successfully
applied as a new kind of mixed-mode stationary phase in liquid chromatography.
This allows an exceptionally flexible adjustment of retention and selectivity by
tuning the experimental conditions. The distinct separation mechanisms were
outlined by selected examples of chromatographic separations in the different
modes. In reversed-phase liquid chromatography, this new stationary phase
presented specific chromatographic performance when evaluated using a Tanaka test
mixture. Seven dinitro aromatic isomers, four steroids, and seven flavonoids were
separated successfully in simple reversed-phase mode. This stationary phase can
also be used in hydrophilic interaction chromatography because of the existing
polar functional groups; for this, nucleosides and their bases were used as a
test mixture. Interestingly, the same nucleosides and bases can also be separated
in per aqueous liquid chromatography using the same stationary phase. Three
ginsenosides including Rg1, Re, and Rb1 were successfully separated in
hydrophilic mode. There is the potential for more applications to benefit from
this useful column.
PMID- 24353083
TI - New calcium-selective smart contrast agents for magnetic resonance imaging.
AB - Calcium plays a vital role in the human body and especially in the central
nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal
cell physiology and health. The deregulation of calcium homeostasis can lead to
neuronal cell death and brain damage. To study this functional role played by
Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have
synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The
agents were found to be highly selective to Ca(2+) in the presence of other
competitive anions and cations in buffer and in physiological fluids. The
structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10
tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O
triacetate (APTRA). The agents are designed to sense Ca(2+) present in
extracellular fluid of the brain where its concentration is relatively high, that
is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls
in the range required to sense and report changes in extracellular Ca(2+) levels
followed by an increase in neural activity. In buffer, with the addition of
Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known
for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by
the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear
magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and
shift experiments. The results obtained confirmed that the large relaxivity
enhancement observed upon Ca(2+) addition is due to the increase of the hydration
state of the complexes together with the slowing down of the molecular rotation
and the retention of a significant contribution of the water molecules of the
second sphere of hydration.
PMID- 24353084
TI - The early spring N uptake of young peach trees (Prunus persica) is affected by
past and current fertilizations and levels of C and N stores.
AB - In deciduous trees, shoot development in early spring is assumed to be achieved
mainly at the expense of nitrogen (N) stores. Indeed, the possible compensation
for poor autumn N storage by early spring N uptake has been little studied. We
therefore determined the dynamics of spring N uptake in relation to spring N
supply, carbon and N storage and shoot development. Young peach trees (Prunus
persica L. Batsch, cv. 'GF305') were raised outdoors in a hydroponic set-up
during the spring and summer, with an excessive N supply. During the autumn, half
of the trees were then N limited. The following spring, the N supply remained
either high or low, or changed from high to low or low to high. Between 6 March
and 13 May, N uptake was measured automatically on an hourly basis, while shoot
growth was monitored once a week. These in situ measurements were completed by
three destructive harvests to assess organ composition in N and total non
structural carbohydrates (TNC). Until the end of April, N uptake was dependent on
the autumn N treatment, being higher in trees that had been N limited in the
autumn. Total non-structural carbohydrate mobilization was also higher in those
trees that had lost at least 17 g TNC by 24 April, while TNC levels in non
limited trees remained stable or even rose. Shoot development, estimated by the
number of elongated axes and leaves per axis, was also slightly delayed by an N
limitation in autumn. After 24 April, N uptake rates increased notably under all
treatments and was determined by the spring N supply. In trees receiving a high N
supply in the spring, the uptake rates also displayed marked short-term
variations. That reduced the differences between treatments and by 13 May no
differences could be evidenced between the trees in terms of organ biomass and
TNC and N contents, whatever the treatment. We concluded that in the early
spring, N uptake may compensate for a deficit of N storage insofar as large
quantities of TNC can be mobilized for that purpose.
PMID- 24353085
TI - Assessment of xylem phenology: a first attempt to verify its accuracy and
precision.
AB - This manuscript aims to evaluate the precision and accuracy of current
methodology for estimating xylem phenology and tracheid production in trees.
Through a simple approach, sampling at two positions on the stem of co-dominant
black spruce trees in two sites of the boreal forest of Quebec, we were able to
quantify variability among sites, between trees and within a tree for different
variables. We demonstrated that current methodology is accurate for the
estimation of the onset of xylogenesis, while the accuracy for the evaluation of
the ending of xylogenesis may be improved by sampling at multiple positions on
the stem. The pattern of variability in different phenological variables and cell
production allowed us to advance a novel hypothesis on the shift in the
importance of various drivers of xylogenesis, from factors mainly varying at the
level of site (e.g., climate) at the beginning of the growing season to factors
varying at the level of individual trees (e.g., possibly genetic variability) at
the end of the growing season.
PMID- 24353086
TI - Effect of short-term food restriction on iron metabolism, relative well-being and
depression symptoms in healthy women.
AB - AIM: The idea that iron deficiency anemia can be recognized in depressive
patients has been around for a few years, as well as negative association between
ferritin levels and depression. Iron deficiency anemia, associated with low iron
intake, has been observed in women using restriction diets, for example in
vegetarians or anorexics. There are no data on the influence of the short-term
food restrictions, observed for example in slimming women, on iron management and
its connection with behavior expressed via changes in the subject's emotional
state. MATERIALS AND METHODS: This study describes the effect of one- and two-day
food restrictions (every 8 days for a period of 48 days) on selected iron
management parameters in the serum and blood of 46 healthy volunteer women (23 in
each group), aged 25.5 +/- 3.0 years, in association with the subjects' self
described emotional status and depression symptoms. The association between iron
parameters and depression was also analyzed. RESULTS: Results show that short
term (2 days) fasting significantly decreases iron concentrations in serum and
hair, as well as levels of ferritin, hemoglobin, hematocrit, red blood cells, and
total iron binding capacity, but the short-term fasting did not influence the
other iron management parameters. Each model of food restrictions also increased
negative feelings towards depression. A significant negative correlation between
serum ferritin levels and depression was found in women who starved for 2 days.
CONCLUSIONS: The study shows that, through an impact on mineral levels, even
short-term food restrictions, as observed in many slimming women and girls, can
be a reason for iron deficiency and also can alter the emotional status of
healthy women. Maybe depression symptoms in anorexia or other eating disorders
patients can be associated with iron deficiencies.
PMID- 24353087
TI - Assessment of the associations between three VEGF polymorphisms and risk of
prostate cancer.
AB - Vascular endothelial growth factor (VEGF) plays a crucial role in the regulation
of angiogenesis and is involved in the development and metastasis of common
cancers. There were several case-controls studies published to assess the
associations of VEGF polymorphisms with risk of prostate cancer, but the findings
were inconsistent. We performed a meta-analysis to provide a comprehensive
assessment of the associations of three VEGF polymorphisms with risk of prostate
cancer. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was
calculated to assess the associations. Eleven individual case-control studies
with a total of 5,209 cases of prostate cancer and 5,233 controls were finally
included into our meta-analysis. Overall, VEGF rs833061 polymorphism was not
associated with risk of prostate cancer (T versus C, OR = 1.14, 95% CI 0.91-1.44,
P = 0.26; TT versus CC, OR = 1.09, 95% CI 0.67-1.76, P = 0.74; TT versus CC/CT:
OR = 1.46, 95% CI 0.67-3.18, P = 0.34; TT/CT versus CC, OR = 1.08, 95% CI 0.82
1.43, P = 0.59). VEGF rs3025039 polymorphism was also not associated with risk of
prostate cancer (T versus C, OR = 1.03, 95% CI 0.91-1.16, P = 0.66; TT versus CC,
OR = 1.82 95% CI 0.16-20.53, P = 0.63; TT versus CC/CT, OR = 2.00, 95% CI 0.18
22.41, P = 0.57; TT/CT versus CC, OR = 0.72, 95% CI 0.38-1.36, P = 0.31). VEGF
rs2010963 polymorphism was not associated with risk of prostate cancer under
three models (C versus G, OR = 1.17, 95% CI 0.92-1.48, P = 0.20; CC versus GG, OR
= 2.28, 95% CI 0.90-5.75, P = 0.08; CC versus GG/GC, OR = 1.57, 95% CI 0.67-3.68,
P = 0.30). In conclusison, current data suggest that those three VEGF
polymorphisms are not obviously associated with risk of prostate cancer.
PMID- 24353088
TI - The association between RASSF1A promoter methylation and prostate cancer:
evidence from 19 published studies.
AB - Ras-associated domain family 1A (RASSF1A) is a putative tumor suppressor gene
located at 3p21.3, and the epigenetic inactivation of RASSF1A by hypermethylation
of CpG islands within the promoter region has been observed in various cancer
types, including prostate cancer (PCa). However, results from published studies
on the association between RASSF1A promoter methylation and PCa risk are
conflicting and inconclusive. Hence, we conducted a meta-analysis of 19 eligible
studies with odds ratio (OR) and its corresponding 95% confidence intervals (95%
CI) in order to investigate the strength of relationship of RASSF1A promoter
methylation with PCa risk and its clinicopathological variables. Overall, the
RASSF1A promoter methylation was significantly associated with PCa risk (OR =
9.58, 95% CI 5.64-16.88, P heterogeneity <0.001) and Gleason score (GS) (OR =
2.58, 95% CI 1.64-4.04, P(heterogeneity) = 0.019). In addition, subgroup analysis
by testing material demonstrated the significant association between RASSF1A
methylation and GS (OR = 3.09, 95% CI 1.92-4.97, P heterogeneity =0.042), PSA
level (OR = 2.75, 95% CI 1.67-4.52, P(heterogeneity) = 0.639), and tumor stage
(OR = 1.74, 95% CI 1.05-2.87, P(heterogeneity) = 0.026) in tissue rather than
urine samples. In conclusion, this meta-analysis suggested that RASSF1A promoter
methylation was significantly associated with an increased risk for PCa;
furthermore, the RASSF1A methylation status in tissue rather than urine was
positively correlated with GS, serum PSA level, and tumor stage, which can be
utilized for the early detection and prognosis prediction of PCa.
PMID- 24353089
TI - Genetic association between p53 codon 72 polymorphism and risk of cutaneous
squamous cell carcinoma.
AB - This study was designed to obtain a conclusive result about the relevance of p53
codon 72 polymorphism to the risk of cutaneous squamous cell carcinoma (SCC). We
performed an updated meta-analysis of 3,792 subjects (1,349 cancer cases and
2,443 controls) to summarize the data available for p53 codon 72 polymorphism and
SCC risk. The association was estimated by odds ratios (ORs) with 95% confidence
intervals (CIs). The meta-analysis showed no statistical significance for SCC
risk associated with any of the genetic models of p53 codon 72 polymorphism. The
analyses by ethnic subgroup also failed to produce significant associations. This
study suggests that p53 codon 72 polymorphism does not appear to represent a
significant susceptibility factor for SCC in Caucasians.
PMID- 24353090
TI - Rhodium(III)-catalyzed ortho alkenylation of N-phenoxyacetamides with N
tosylhydrazones or diazoesters through C-H activation.
AB - A coupling reaction of N-phenoxyacetamides with N-tosylhydrazones or diazoesters
through Rh(III) -catalyzed C?H activation is reported. In this reaction, ortho
alkenyl phenols were obtained in good yields and with excellent regio- and
stereoselectivity. Rh-carbene migratory insertion is proposed as the key step in
the reaction mechanism.
PMID- 24353091
TI - The combination of anatomy and physiology in predicting the outcomes of
velopharyngeal surgery.
AB - OBJECTIVES/HYPOTHESIS: To explore whether the variables resulting from anatomical
and physiological examinations can be combined to predict the outcomes of
velopharyngeal surgery for obstructive sleep apnea (OSA). STUDY DESIGN:
Prospective design with a retrospective review. METHODS: A total of 119 patients
with OSA received velopharyngeal surgery, including revised
uvulopalatopharyngoplasty with uvula preservation and transpalatal advancement
pharyngoplasty. The preoperative examinations of these patients, including
polysomnography (PSG), physical examination, and three-dimensional computer
tomography (3-D CT), were obtained for analysis. RESULTS: The overall success
rate was 62.2%. Three factors were found to be predictive in treatment outcomes
(P<0.05). These were tonsil size, the percentage of time with oxygen saturation
below 90% (CT90), and the vertical distance between the lower edge of the
mandible and the lower edge of the hyoid (MH). After changing CT90 and MH into
level variables, another regression analysis was performed and the result
suggested that all three level variables could be included. A scoring system was
then created based on these three variables and their odds ratio values. The
total scores of all patients were calculated by the following equation: Total
score=2.7 tonsil size (score)+2.2 CT90 (score)+1.6 MH (score). The differences in
success rates among patients with total scores of <14, 14 to 17, 17 to 22, and
>=22 were all significant (P<0.05). CONCLUSION: The anatomy of the pharynx and
the physiology of OSA are both important in deciding outcomes of velopharyngeal
surgery. Variables that could represent these two aspects can be combined to
better guide patient selections. LEVEL OF EVIDENCE: 4.
PMID- 24353092
TI - Introducing the AASLD President: Adrian Di Bisceglie.
PMID- 24353093
TI - Tips for endoscopic ultrasound-guided fine needle aspiration of various
pancreatic lesions.
AB - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a well
established procedure for diagnosis of pancreatic solid masses. This technique is
highly accurate and safe and can be performed uneventfully in most cases.
However, factors such as unstable scope position, inappropriate location of the
lesion, lesion mobility, and lesion characteristics may complicate the procedure.
To overcome such difficulties, it is necessary to select the most suitable needle
and consider several technical points according to each situation. We introduce
our standard technique for EUS-FNA and provide several tips for ensuring a
successful procedure.
PMID- 24353094
TI - Review of nutritional supplements for the treatment of bipolar depression.
AB - Many patients view psychotropics with skepticism and fear and view nutritional
supplements as more consistent with their values and beliefs. The purpose of this
review was to critically evaluate the evidence base for nutritional supplements
in the treatment of bipolar depression (BD). A literature search for all
randomized, controlled clinical trials using nutritional supplements in the
treatment of BD was conducted via PubMed and Ovid MEDLINE computerized database.
The studies were organized into essential nutrients/minerals, nonessential
nutrients, and combinations of nutritional products. Among essential
nutrients/minerals, omega-3-fatty acids (O3FAs) have the strongest evidence of
efficacy for bipolar depression, although some studies failed to find positive
effects from O3FAs. Weak evidence supports efficacy of vitamin C whereas no data
support the usefulness of folic acid and choline. Among nonessential nutrients,
cytidine is the least supported treatment. Studies of N-acetylcysteine have not
resolved its efficacy in treating acute depressive episodes relative to placebo.
However, one study demonstrates its potential to improve depressive symptoms over
time and the other, though nonsignificant, suggests it has a prophylactic effect.
Studies of inositol have been mostly negative, except for 1 study. Those that
were negative were underpowered but demonstrated numerically positive effects for
inositol. There is no evidence that citicholine is efficacious for uncomplicated
BD depression, though it may have value for comorbid substance abuse among BD
patients. Finally, combination O3FA-cytidine lacks evidence of efficacy. The
findings of this review do not support the routine use of nutritional supplements
in the treatment or prophylaxis of BD depression. Studies with more rigorous
designs are required before definitive conclusions can be made. Despite the
inadequacy of the existing data, clinicians should remain open to the value of
nutritional supplements: after all, lithium is a mineral too.
PMID- 24353095
TI - Peer-professional first person account: before psychosis--schizoid personality
from the inside.
PMID- 24353096
TI - Prevalence and clinical significance of DSM-5-attenuated psychosis syndrome in
adolescents and young adults in the general population: the Bern Epidemiological
At-Risk (BEAR) study.
AB - OBJECTIVE: Section III of the Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (DSM-5) lists attenuated psychosis syndrome as a
condition for further study. One important question is its prevalence and
clinical significance in the general population. METHOD: Analyses involved 1229
participants (age 16-40 years) from the general population of Canton Bern,
Switzerland, enrolled from June 2011 to July 2012. "Symptom," "onset/worsening,"
"frequency," and "distress/disability" criteria of attenuated psychosis syndrome
were assessed using the structured interview for psychosis-risk syndromes.
Furthermore, help-seeking, psychosocial functioning, and current nonpsychotic
axis I disorders were surveyed. Well-trained psychologists performed assessments
using the computer-assisted telephone interviewing technique. RESULTS: The
symptom criterion was met by 12.9% of participants, onset/worsening by 1.1%,
frequency by 3.8%, and distress/disability by 7.0%. Symptom, frequency, and
distress/disability were met by 3.2%. Excluding trait-like attenuated psychotic
symptoms (APS) decreased the prevalence to 2.6%, while adding onset/worsening
reduced it to 0.3%. APS were associated with functional impairments, current
mental disorders, and help-seeking although they were not a reason for help
seeking. These associations were weaker for attenuated psychosis syndrome.
CONCLUSIONS: At the population level, only 0.3% met current attenuated psychosis
syndrome criteria. Particularly, the onset/worsening criterion, originally
included to increase the likelihood of progression to psychosis, lowered its
prevalence. Because progression is not required for a self-contained syndrome, a
revision of the restrictive onset criterion is proposed to avoid the exclusion of
2.3% of persons who experience and are distressed by APS from mental health care.
Secondary analyses suggest that a revised syndrome would also possess higher
clinical significance than the current syndrome.
PMID- 24353098
TI - Reply to Preoperative BRAF(V600E) mutation screening is unlikely to alter initial
surgical treatment of patients with indeterminate thyroid nodules: a prospective
case series of 960 patients.
PMID- 24353097
TI - Altered cortical thickness related to clinical severity but not the untreated
disease duration in schizophrenia.
AB - Although previous studies have reported deficits in the gray matter volume of
schizophrenic patients, it remains unclear whether these deficits occur at the
onset of the disease, before treatment, and whether they are progressive over the
duration of untreated disease. Furthermore, the gray matter volume represents the
combinations of cortical thickness and surface area; these features are believed
to be influenced by different genetic factors. However, cortical thickness and
surface area in antipsychotic-naive first-episode schizophrenic patients have
seldom been investigated. Here, the cortical thicknesses and surface areas of 128
antipsychotic-naive first-episode schizophrenic patients were compared with 128
healthy controls. The patients exhibited significantly lower cortical thickness,
primarily in the bilateral prefrontal and parietal cortex, and increased
thickness in the bilateral anterior temporal lobes, left medial orbitofrontal
cortex, and left cuneus. Furthermore, decreased cortical thickness was related to
positive schizophrenia symptoms but not to the severity of negative symptoms and
the untreated disease duration. No significant difference of surface area was
observed between the 2 groups. Thus, without the confounding factors of
medication and illness progression, this study provides further evidence to
support anatomical deficits in the prefrontal and parietal cortex early in course
of the illness. The increased thicknesses of the bilateral anterior temporal
lobes may represent a compensatory factor or may be an early-course neuronal
pathology caused by preapoptotic osmotic changes or hypertrophy. Furthermore,
these anatomical deficits are crucial to the pathogenesis of positive symptoms
and relatively stable instead of progressing during the early stages of the
disease.
PMID- 24353099
TI - A prophet to modern medicine: Ernest Amory Codman.
PMID- 24353100
TI - The Cochrane collaboration at 20.
PMID- 24353101
TI - The year of Francis.
PMID- 24353102
TI - Can India save its Parsi community with assisted reproduction?
PMID- 24353103
TI - Medical education companies got $170m in grants from 14 drug firms in 2010, study
finds.
PMID- 24353104
TI - Doctors need to take the lead on poverty's effects on health.
PMID- 24353105
TI - UK cancer death rates drop by more than a fifth over 20 years.
PMID- 24353106
TI - Care Bill could lead to "backdoor" reconfiguration of NHS services, says BMA.
PMID- 24353107
TI - Water-based exercise training for chronic obstructive pulmonary disease.
AB - BACKGROUND: Land-based exercise training improves exercise capacity and quality
of life in people with chronic obstructive pulmonary disease (COPD). Water-based
exercise training is an alternative mode of physical exercise training that may
appeal to the older population attending pulmonary rehabilitation programmes,
those who are unable to complete land-based exercise programmes and people with
COPD with comorbid physical and medical conditions. OBJECTIVES: To assess the
effects of water-based exercise training in people with COPD. SEARCH METHODS: A
search of the Cochrane Airways Group Specialised Register of trials, which is
derived from systematic searches of bibliographic databases, including the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
CINAHL, AMED and PsycINFO, was conducted (from inception to August 2013).
Handsearching was done to identify further qualifying studies from reference
lists of relevant studies. SELECTION CRITERIA: Review authors included randomised
or quasi-randomised controlled trials in which water-based exercise training of
at least four weeks' duration was compared with no exercise training or any other
form of exercise training in people with COPD. Swimming was excluded. DATA
COLLECTION AND ANALYSIS: We used standard methodological procedures expected by
The Cochrane Collaboration. MAIN RESULTS: Five studies were included with a total
of 176 participants (71 people participated in water-based exercise training and
54 in land-based exercise training; 51 completed no exercise training). All
studies compared supervised water-based exercise training versus land-based
exercise training and/or no exercise training in people with COPD (with average
forced expiratory volume in one second (FEV1) %predicted ranging from 39% to
62%). Sample sizes ranged from 11 to 53 participants. The exercise training
programmes lasted from four to 12 weeks, and the mean age of participants ranged
from 57 to 73 years. A moderate risk of bias was due to lack of reporting of
randomisation, allocation and blinding procedures in some studies, as well as
small sample sizes.Compared with no exercise, water-based exercise training
improved the six-minute walk distance (mean difference (MD) 62 metres; 95%
confidence interval (CI) 44 to 80 metres; three studies; 99 participants;
moderate quality evidence), the incremental shuttle walk distance (MD 50 metres;
95% CI 20 to 80 metres; one study; 30 participants; high quality evidence) and
the endurance shuttle walk distance (MD 371 metres; 95% CI 121 to 621 metres; one
study; 30 participants; high quality evidence). Quality of life was also improved
after water-based exercise training compared with no exercise (standardised mean
difference (SMD) -0.97, 95% CI -0.37 to -1.57; two studies; 49 participants; low
quality evidence). Compared with land-based exercise training, water-based
exercise training did not significantly change the six-minute walk distance (MD
11 metres; 95% CI -11 to 33 metres; three studies; 62 participants; moderate
quality evidence) or the incremental shuttle walk distance (MD 9 metres; 95% CI
15 to 34 metres; two studies; 59 participants; low quality evidence). However,
the endurance shuttle walk distance improved following water-based exercise
training compared with land-based exercise training (MD 313 metres; 95% CI 232 to
394 metres; two studies; 59 participants; moderate quality evidence). No
significant differences were found between water-based exercise training and land
based exercise training for quality of life, as measured by the St George's
Respiratory Questionnaire or by three of four domains of the Chronic Respiratory
Disease Questionnaire (CRDQ); however, the fatigue domain of the CRDQ showed a
statistically significant difference in favour of water-based exercise (MD -3.00;
95% CI -5.26 to -0.74; one study; 30 participants). Only one study reported long
term outcomes after water-based exercise training for quality of life and body
composition, and no significant change was observed between baseline results and
six-month follow-up results. One minor adverse event was reported for water-based
exercise training (based on reporting from two studies; 20 participants). Impact
of disease severity could not be examined because data were insufficient.
AUTHORS' CONCLUSIONS: There is limited quality evidence that water-based exercise
training is safe and improves exercise capacity and quality of life in people
with COPD immediately after training. There is limited quality evidence that
water-based exercise training offers advantages over land-based exercise training
in improving endurance exercise capacity, but we remain uncertain as to whether
it leads to better quality of life. Little evidence exists examining the long
term effect of water-based exercise training.
PMID- 24353108
TI - Cognitive performance is associated with left ventricular function in older
chronic hemodialysis patients: result of a pilot study.
AB - BACKGROUND: Cognitive impairment is a common finding in end-stage renal disease
patients on chronic hemodialysis, but data on the associated factors are still
scanty. AIMS: The present study evaluated the association between cognitive
function and left ventricular systolic function in hemodialysis patients.
METHODS: We enrolled 72 patients admitted to the Hemodialysis Unit of the
Catholic University, Rome. Cognitive performance was evaluated using the Mini
Mental State Examination (MMSE); a cutoff of 24 was used to diagnose cognitive
impairment. Left ventricular ejection fraction (LVEF) was assessed by
echocardiography. Multivariable linear and logistic regressions were adopted to
assess the adjusted association between cognitive performance and LVEF. Also,
linear discriminant analysis was performed to ascertain the cutoff level of LVEF
which best predicted cognitive impairment. RESULTS: Cognitive impairment was
found in 37 (51 %) patients. According to linear regression, MMSE was
independently associated with LVEF (B = 0.06; 95 % CI = 0.01-0.12; P = 0.040).
Logistic regression confirmed the inverse association between LVEF and cognitive
impairment (OR = 0.87; 95 % CI = 0.78-0.98; P = 0.022). In linear discriminant
analysis, the LVEF cutoff level that best predicted cognitive impairment was <=51
%. CONCLUSION: Cognitive impairment is a common finding in hemodialysis patients.
Even mildly depressed LVEF is independently associated with cognitive impairment.
This association and its potential therapeutic implications should be assessed in
dedicated studies.
PMID- 24353109
TI - Invasive neurostimulation in stroke rehabilitation.
AB - The last decade has seen a growing interest in adjuvant treatments that
synergistically influence mechanisms underlying rehabilitation of paretic upper
limb in stroke. One such approach is invasive neurostimulation of spared cortices
at the periphery of a lesion. Studies in animals have shown that during training
of paretic limb, adjuvant stimulation targeting the peri-infarct circuitry
enhances mechanisms of its reorganization, generating functional advantage.
Success of early animal studies and clinical reports, however, failed to
translate to a phase III clinical trial. As lesions in humans are diffuse, unlike
many animal models, peri-infarct circuitry may not be a feasible, or consistent
target across most. Instead, alternate mechanisms, such as changing transcallosal
inhibition between hemispheres, or reorganization of other viable regions in
motor control, may hold greater potential. Here, we review comprehensive
mechanisms of clinical recovery and factors that govern which mechanism(s) become
operative when. We suggest novel approaches that take into account a patient's
initial clinical-functional state, and findings from neuroimaging and
neurophysiology to guide to their most suitable mechanism for ideal targeting.
Further, we suggest new localization schemes, and bypass strategies that
indirectly target peri-lesional circuitry, and methods that serve to counter
technical and theoretical challenge in identifying and stimulating such targets
at the periphery of infarcts in humans. Last, we describe how stimulation may
modulate mechanisms differentially across varying phases of recovery- a temporal
effect that may explain missed advantage in clinical trials and help plan for the
next stage. With information presented here, future trials would effectively be
able to target patient's specific mechanism(s) with invasive (or noninvasive)
neurostimulation for the greatest, most consistent benefit.
PMID- 24353110
TI - Developing biomarkers in mood disorders research through the use of rapid-acting
antidepressants.
AB - An impediment to progress in mood disorders research is the lack of analytically
valid and qualified diagnostic and treatment biomarkers. Consistent with the
National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC)
initiative, the lack of diagnostic biomarkers has precluded us from moving away
from a purely subjective (symptom-based) toward a more objective diagnostic
system. In addition, treatment response biomarkers in mood disorders would
facilitate drug development and move beyond trial-and-error toward more
personalized treatments. As such, biomarkers identified early in the
pathophysiological process are proximal biomarkers (target engagement), while
those occurring later in the disease process are distal (disease pathway
components). One strategy to achieve this goal in biomarker development is to
increase efforts at the initial phases of biomarker development (i.e. exploration
and validation) at single sites with the capability of integrating multimodal
approaches across a biological systems level. Subsequently, resultant putative
biomarkers could then undergo characterization and surrogacy as these latter
phases require multisite collaborative efforts. We have used multimodal
approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal
neuroimaging, neuropsychopharmacological challenge paradigms and clinical
predictors - to explore potential predictor and mediator/moderator biomarkers of
the rapid-acting antidepressants ketamine and scopolamine. These exploratory
biomarkers may then be used for a priori stratification in larger multisite
controlled studies during the validation and characterization phases with the
ultimate goal of surrogacy. In sum, the combination of target engagement and well
qualified disease-related measures are crucial to improve our pathophysiological
understanding, personalize treatment selection, and expand our armamentarium of
novel therapeutics.
PMID- 24353112
TI - A spatial scan statistic for survival data based on Weibull distribution.
AB - The spatial scan statistic has been developed as a geographical cluster detection
analysis tool for different types of data sets such as Bernoulli, Poisson,
ordinal, normal and exponential. We propose a scan statistic for survival data
based on Weibull distribution. It may also be used for other survival
distributions, such as exponential, gamma, and log normal. The proposed method is
applied on the survival data of tuberculosis patients for the years 2004-2005 in
Nainital district of Uttarakhand, India. Simulation studies reveal that the
proposed method performs well for different survival distribution functions.
PMID- 24353114
TI - Radiation-induced synthesis of nanostructured conjugated polymers in aqueous
solution: fundamental effect of oxidizing species.
AB - Synthesis of conjugated poly(3,4-ethylenedioxythiophene) (PEDOT) polymers is
achieved through the radiolysis of N2O-saturated aqueous solutions of 3,4
ethylenedioxythiophene by using two different oxidizing species: HO(.) (hydroxyl)
and N3(.) (azide) radicals. Both oxidative species lead to self-assembled
polymers that are evidenced in solution by cryotransmission electron microscopy
and UV/Vis absorption spectroscopy and, after centrifugation and deposition, by
scanning electron microscopy and attenuated total reflectance FTIR techniques.
Whereas HO(.) radicals lead to PEDOT-OH globular nanostructures with hydrophilic
properties, N3(.) radicals enable the formation of amphiphilic PEDOT-N3 fibrillar
nanostructures. These results, which highlight the differences in the
intermolecular interaction behaviors of the two kinds of PEDOT polymers, are
discussed in terms of polymerization mechanisms.
PMID- 24353113
TI - Randomized controlled trial on timing and number of sampling for bile aspiration
cytology.
AB - BACKGROUND: The issue on timing and number of bile sampling for exfoliative bile
cytology is still unsettled. METHODS: A total of 100 patients with
cholangiocarcinoma undergoing resection after external biliary drainage were
randomized into two groups: a 2-day group where bile was sampled five times per
day for 2 days; and a 10-day group where bile was sampled once per day for 10
days (registered University Hospital Medical Information Network/ID 000005983).
The outcome of 87 patients who underwent laparotomy was analyzed, 44 in the 2-day
group and 43 in the 10-day group. RESULTS: There were no significant differences
in patient characteristics between the two groups. Positivity after one sampling
session was significantly lower in the 2-day group than in the 10-day group (17.0
+/- 3.7% vs. 20.7 +/- 3.5%, P = 0.034). However, cumulative positivity curves
were similar and overlapped each other between both groups. The final cumulative
positivity by the 10th sampling session was 52.3% in the 2-day group and 51.2% in
the 10-day group. We observed a small increase in cumulative positivity after the
5th or 6th session in both groups. CONCLUSIONS: Bile cytology positivity is
unlikely to be affected by sample time.
PMID- 24353111
TI - Novel insights on interactions between folate and lipid metabolism.
AB - Folate is an essential B vitamin required for the maintenance of AdoMet-dependent
methylation. The liver is responsible for many methylation reactions that are
used for post-translational modification of proteins, methylation of DNA, and the
synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions
where methylation capacity is compromised, including folate deficiency, are
associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic
fatty liver disease and steatohepatitis. In addition, folate intake and folate
status have been associated with changes in the expression of genes involved in
lipid metabolism, obesity, and metabolic syndrome. In this review, we provide
insight on the relationship between folate and lipid metabolism, and an outlook
for the future of lipid-related folate research.
PMID- 24353115
TI - Thousands of NHS staff made redundant have been rehired despite large payoffs.
PMID- 24353116
TI - Antibiotic use for irreversible pulpitis.
AB - BACKGROUND: Irreversible pulpitis, which is characterised by acute and intense
pain, is one of the most frequent reasons that patients attend for emergency
dental care. Apart from removal of the tooth, the customary way of relieving the
pain of irreversible pulpitis is by drilling into the tooth, removing the
inflamed pulp (nerve) and cleaning the root canal. However, a significant number
of dentists continue to prescribe antibiotics to stop the pain of irreversible
pulpitis. OBJECTIVES: To assess the effects of systemic antibiotics for
irreversible pulpitis. SEARCH METHODS: We searched the Cochrane Oral Health
Group's Trials Register (to 5 September 2013); the Cochrane Central Register of
Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via
OVID (1946 to 5 September 2013); EMBASE via OVID (1980 to 5 September 2013) and
the US National Institutes of Health Trials Register (http://clinicaltrials.gov).
There were no language restrictions in the searches of the electronic databases.
SELECTION CRITERIA: Randomised controlled trials which compared pain relief with
systemic antibiotics and analgesics, against placebo and analgesics in the acute
preoperative phase of irreversible pulpitis. DATA COLLECTION AND ANALYSIS: Two
review authors screened studies and extracted data independently. We assessed the
quality of the evidence of included studies using GRADEPro software. Pooling of
data was not possible and a descriptive summary is presented. MAIN RESULTS: One
trial assessed at low risk of bias, involving 40 participants was included in
this update of the review. The quality of the body of evidence was rated low for
the different outcomes. There was a close parallel distribution of the pain
ratings in both the intervention and placebo groups over the seven-day study
period. There was insufficient evidence to claim or refute a benefit for
penicillin for pain intensity. There was no significant difference in the mean
total number of ibuprofen tablets over the study period: 9.2 (standard deviation
(SD) 6.02) in the penicillin group versus 9.6 (SD 6.34) in the placebo group;
mean difference -0.40 (95% confidence interval (CI) -4.23 to 3.43; P value =
0.84). This applied equally for the mean total number of Tylenol tablets: 6.9 (SD
6.87) used in the penicillin group versus 4.45 (SD 4.82) in the placebo group;
mean difference 2.45 (95% CI -1.23 to 6.13; P value = 0.19). Our secondary
outcome on reporting of adverse events was not addressed in this study. AUTHORS'
CONCLUSIONS: This systematic review which was based on one low powered small
sample trial assessed as a low risk of bias, illustrates that there is
insufficient evidence to determine whether antibiotics reduce pain or not
compared to not having antibiotics. The results of this review confirm the
necessity for further larger sample and methodologically sound trials that can
provide additional evidence as to whether antibiotics, prescribed in the
preoperative phase, can affect treatment outcomes for irreversible pulpitis.
PMID- 24353117
TI - Time of effect duration and administration interval for sitagliptin in patients
with kidney failure.
AB - A measure correlating the time course of the effect with the time course of
concentrations could be helpful in drug dosing. We propose a new equation with
explicit solutions for calculating the effect duration. A specific effect
fraction is selected (fr) and the time of fractional effect duration (TED.fr) can
be derived as a function of the elimination half-life by combining linear
elimination kinetics with sigmoid effect dynamics. This new measure is applied to
the example of sitagliptin, whose elimination half-life increases from 10.1 to
28.4 h in patients with kidney failure. Under normal multiple-dose conditions,
the 24-h sitagliptin administration interval corresponds to a 0.90 time of
fractional effect duration (TED.90). A dose reduction to one-fourth or 25 mg
every 24 h is proposed for patients with kidney failure; this results in a TED.90
of 45 h, i.e. 21 h longer than the proposed 24-h administration interval (+88 %).
The proportional dosing alternative of 100 mg every 96 h would result in a TED.90
of 64 h, which is 32 h less than the 96-h administration interval (-33 %). With a
half dose of 50 mg and a doubled administration interval of 48 h, the TED.90 is
51 h in kidney failure, only 3 h longer than the latter administration interval
(+6 %). We conclude that our general equation can be applied to rapidly calculate
the specific time of effect duration for the different dose schedules.
PMID- 24353120
TI - Ablation of residual Barrett's epithelium after endoscopic resection: a
randomized long-term follow-up study of argon plasma coagulation vs. surveillance
(APE study).
AB - BACKGROUND AND STUDY AIM: It is commonly assumed that ablation of any remaining
Barrett's epithelium after endoscopic resection of early Barrett's neoplasia
improves outcome by reducing the rate of metachronous lesions, but this has not
yet been evaluated in a randomized trial. The aim of this study was to compare
argon plasma coagulation (APC) with surveillance only for the management of
residual Barrett's epithelium following endoscopic resection. PATIENTS AND
METHODS: Patients in whom focal early Barrett's neoplasia (high grade
intraepithelial neoplasia [HGIN] or mucosal cancer) had been curatively resected
by endoscopy were randomly assigned to undergo ablation of the residual Barrett's
segment by APC or surveillance only; pH-metry-adjusted proton pump inhibitor
therapy was administered in both groups. The main outcome parameter was
recurrence-free survival. Follow-up endoscopies with biopsies in cases of further
residual Barrett's epithelium were carried out at 6-monthly intervals in both
groups. RESULTS: A total of 63 patients (57 male [90.5%]) were included in the
study (ablation group n=33; surveillance group n=30). For complete Barrett's
ablation, a mean number of 4+/-1.6 APC sessions were required (range 2-7). The
mean follow-up duration did not differ significantly between ablation (28.2+/
13.7 months, range 0-44) and surveillance patients (24.7+/-14.8 months, range 0
45; P=0.159). The number of secondary lesions was 1 in the ablation group (3%),
and 11 in the surveillance group (36.7%), leading to significantly higher
recurrence-free survival for the patients undergoing ablation (P=0.005).
CONCLUSIONS: Thermal ablation of residual Barrett's epithelium leads to a
significant reduction in neoplasia recurrence rate compared with a surveillance
strategy during a limited follow-up of 2 years. A longer follow-up duration may
have led to a relatively higher rate of secondary neoplasia in both groups of
patients.
PMID- 24353121
TI - Argon plasma coagulation for Barrett's neoplasia: the right hot ingredient for a
successful recipe?
PMID- 24353122
TI - A multicenter study on the role of direct retrograde cholangioscopy in patients
with inconclusive endoscopic retrograde cholangiography.
AB - BACKGROUND AND STUDY AIMS: Direct retrograde cholangioscopy (DRC) may improve the
diagnostic and therapeutic yield of endoscopic retrograde cholangiography (ERC)
but safety, feasibility, and outcome are unknown. PATIENTS AND METHODS: All
consecutive patients who underwent DRC at three tertiary endoscopy centers for
inconclusive findings at ERC were included in this retrospective analysis.
Ultraslim endoscopes (FujiFilm EG 530NP; Olympus GIF XP180; GIF N180) were used
by the peroral route for intubating all accessible bile ducts. Success rate,
usefulness in diagnosis and therapy, and safety of DRC were assessed in terms of
technical and clinical parameters and therapeutic vs. diagnostic indication.
RESULTS: DRC was performed in 130 cases (89 patients). CO2 insufflation and an
anchoring balloon were used in 66.9% and 97.7% of cases, respectively. Intubation
of the papilla was successful in 115 of 130 (88.5%) cases, and the aim of the DRC
investigation was accomplished in 105 cases (80.8%). DRC-guided biopsies were
taken in 53 cases (40.8%), and a therapeutic intervention was performed in 32
cases (24.6%). The initial diagnosis was revised by DRC in 18 of 69 patients
(26.1%) with indeterminate biliary stricture. Complications were observed in 10
cases (7.7%), including cholangitis (n=2; 1.5%), bleeding (n=2; 1.5%), and pain,
hypoxia, bradyarrhythmia, air embolism, and perforation of an intrahepatic and an
extrahepatic bile duct (1 each; 0.8%). There was no mortality associated with
DRC. CONCLUSIONS: DRC was successfully performed for the diagnosis and treatment
of biliary disease that had eluded diagnosis with conventional ERC. DRC impacted
on clinical decision making. The complication rate was low and similar to other
cholangioscopy techniques.
PMID- 24353123
TI - Early detection of pancreatic cancer in patients with intraductal papillary
mucinous neoplasms: the pivotal role of endoscopic ultrasound.
PMID- 24353124
TI - CO2 insufflation during single-balloon enteroscopy: a multicenter randomized
controlled trial.
AB - BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation has previously been
shown to have advantages over air insufflation in terms of procedure-related pain
and oral insertion depth during double-balloon enteroscopy. The aim of this
prospective study was to evaluate the performance of CO2 vs. air insufflation
during single-balloon enteroscopy. PATIENTS AND METHODS: This study was a
randomized European multicenter trial (ClinicalTrials.gov: NCT01524055). Patients
and endoscopists were blinded to the type of insufflation gas used. Patient
discomfort during and after the procedure was scored using a visual analog scale.
RESULTS: A total of 107 patients were enrolled in the study (52 in the CO2 group
and 55 in the air group). Patient characteristics were comparable in both groups.
The mean (+/-SD) oral intubation depth was not significantly deeper in the CO2
group vs. the air group (254+/-80 vs. 238+/-55 cm; P=0.726). However, in patients
with previous abdominal surgery, oral intubation depth was significantly higher
in the CO2 group compared with the air group (258+/-84 vs. 192+/-42 cm; P<0.05).
In patients undergoing SBE via the anal approach, CO2 showed no significant
difference in intubation depth compared with air insufflation (86+/-67 vs. 110+/
68 cm; P=0.155). The diagnostic yield was comparable (CO2 67%; air 73%).
Procedure times, dosage of sedation, and therapeutic interventions did not differ
between the two groups. Patients in the CO2 group reported less pain than those
in the air group. CONCLUSIONS: This study demonstrated an advantage of using CO2
insufflation during single-balloon enteroscopy in patients with a history of
previous abdominal surgery. Overall, single-balloon enteroscopy was a well
tolerated procedure that may benefit from the use of CO2 insufflation to reduce
post-procedural pain.
PMID- 24353125
TI - Economic crisis: the right time to widen endoscopic ultrasound utilization.
PMID- 24353126
TI - Is closure of only the mucosal layer really sufficient?
PMID- 24353129
TI - Frequency correction method for improved spatial correlation of hyperpolarized
13C metabolites and anatomy.
AB - Blip-reversed echo-planar imaging (EPI) is investigated as a method for measuring
and correcting the spatial shifts that occur due to bulk frequency offsets in
(13)C metabolic imaging in vivo. By reversing the k-space trajectory for every
other time point, the direction of the spatial shift for a given frequency is
reversed. Here, mutual information is used to find the 'best' alignment between
images and thereby measure the frequency offset. Time-resolved 3D images of
pyruvate/lactate/urea were acquired with 5 s temporal resolution over a 1 min
duration in rats (N = 6). For each rat, a second injection was performed with the
demodulation frequency purposely mis-set by +35 Hz, to test the correction for
erroneous shifts in the images. Overall, the shift induced by the 35 Hz frequency
offset was 5.9 +/- 0.6 mm (mean +/- standard deviation). This agrees well with
the expected 5.7 mm shift based on the 2.02 ms delay between k-space lines
(giving 30.9 Hz per pixel). The 0.6 mm standard deviation in the correction
corresponds to a frequency-detection accuracy of 4 Hz. A method was presented for
ensuring the spatial registration between (13)C metabolic images and conventional
anatomical images when long echo-planar readouts are used. The frequency
correction method was shown to have an accuracy of 4 Hz. Summing the spatially
corrected frames gave a signal-to-noise ratio (SNR) improvement factor of 2 or
greater, compared with the highest single frame.
PMID- 24353128
TI - The effect of gender, age, and symptom severity in late-life depression on the
risk of all-cause mortality: the Bambui Cohort Study of Aging.
AB - BACKGROUND: Increased mortality risk and its moderators is an important, but
still under recognized, negative outcome of late-life depression (LLD).
Therefore, we aimed to evaluate whether LLD is a risk factor for all-cause
mortality in a population-based study with over 10 years of follow-up, and
addressed the moderating effect of gender and symptom severity on mortality risk.
METHODS: This analysis used data from the Bambui Cohort Study of Aging. The study
population comprised 1.508 (86.5%) of all eligible 1.742 elderly residents.
Depressive symptoms were annually evaluated by the GHQ-12, with scores of five or
higher indicating clinically significant depression. From 1997 to 2007, 441
participants died during 10,648 person-years of follow-up. We estimated the
hazard ratio for mortality risk by Cox regression analyses. RESULTS: Depressive
symptoms were a risk factor for all-cause mortality after adjusting for
confounding lifestyle and clinical factors (adjusted HR = 1.24 CI95% [1.00-1.55],
P = .05). Mortality risk was significantly elevated in men (adjusted HR = 1.45
CI95% [1.01-2.07], P = 0.04), but not in women (adjusted HR = 1.13 CI95% [0.84
1.48], P = 0.15). We observed a significant interaction between gender and
depressive symptoms on mortality risk ((HR = 1.72 CI95% [1.18-2.49], P = 0.004).
CONCLUSION: The present study provides evidence that LLD is a risk factor for all
cause mortality in the elderly, especially in men. The prevention and adequate
treatment of LLD may help to reduce premature disability and death among elders
with depressive symptoms.
PMID- 24353130
TI - Reclassification of predictions for uncovering subgroup specific improvement.
AB - Risk prediction models play an important role in prevention and treatment of
several diseases. Models that are in clinical use are often refined and improved.
In many instances, the most efficient way to improve a successful model is to
identify subgroups for which there is a specific biological rationale for
improvement and tailor the improved model to individuals in these subgroups, an
approach especially in line with personalized medicine. At present, we lack
statistical tools to evaluate improvements targeted to specific subgroups. Here,
we propose simple tools to fill this gap. First, we extend a recently proposed
measure, the Integrated Discrimination Improvement, using a linear model with
covariates representing the subgroups. Next, we develop graphical and numerical
tools that compare reclassification of two models, focusing only on those
subjects for whom the two models reclassify differently. We apply these
approaches to BRCAPRO, a genetic risk prediction model for breast and ovarian
cancer, using data from MD Anderson Cancer Center. We also conduct a simulation
study to investigate properties of the new reclassification measure and compare
it with currently used measures. Our results show that the proposed tools can
successfully uncover subgroup specific model improvements.
PMID- 24353131
TI - Utility of fine-needle aspiration and core biopsy with touch preparation in the
diagnosis of renal lesions.
AB - BACKGROUND: Cytologic evaluation by fine-needle aspiration (FNA) and core biopsy
(CB) with touch preparation (TP) is used in the diagnosis of renal lesions.
METHODS: Consecutive image-guided FNA and CB, with or without TP, of renal
lesions were reviewed. The cytology diagnoses were correlated with the radiology,
surgical specimens, and clinical course. RESULTS: A total of 154 procedures (76
FNA, 17 FNA+CB, 46 CB+TP, 15 FNA+CB+TP) were performed for lesions with benign
(21), malignant (123), or indeterminate (10) radiology. Specimen adequacy was
satisfactory in 86% of FNAs (93 of 108), 95% of TPs (58 of 61), and 94% of CBs
(73 of 78), and is statistically significant for CB with or without TP versus FNA
(P = .045). In the subset with concerning radiology (n = 133), specimen adequacy
was satisfactory in 83% of FNAs (72 of 87), 95% of TPs (58 of 61), and 94% of CBs
(73 of 78) (P = .006 for CB +/- TP versus FNA), and procedures were diagnostic in
79% of FNAs (69 of 87), 90% of 61 TPs (55 of 61) and 90% of CBs (70 of 78) (P =
.02 for CB +/- TP versus FNA). Renal cell carcinoma subtype was reported in 63%
of FNA (19 of 30) versus 88% of CB +/- TP (43 of 49) (P = .01), and Fuhrman
nuclear grade was reported only on CB. The cytology diagnoses correlated with
surgical specimens in 94% (33 of 35). The most common treatment was ablation of
small (3.0 +/- 1.3 cm) masses (n = 47). CONCLUSIONS: Compared with FNA, CB and TP
have higher adequacy and diagnostic yield and provide more diagnostic
information. Cytology diagnoses are highly accurate when correlated to surgical
specimens.
PMID- 24353132
TI - Effect of combined treatment with the epirubicin-incorporating micelles (NC-6300)
and 1,2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016) on a
human gastric cancer model.
AB - Anticancer agent-incorporating polymeric micelles accumulate effectively in
tumors via the enhanced permeability and retention effect to exert potent
antitumor effects. However, combined use of such micelles has not been
elucidated. We compared the effect of combining the epirubicin-incorporating
micelle NC-6300 and 1,2-diaminocyclohexane platinum (II) (oxaliplatin parent
complex)-incorporating micelle NC-4016 (NCs) with that of epirubicin and
oxaliplatin (E/O) in 44As3Luc cells using the combination index method. The in
vivo antitumor activities of NCs and E/O were evaluated in mice bearing 44As3Luc
xenografts. Pharmacokinetic analysis was performed by high-performance liquid
chromatography and mass spectrometry. Cardiotoxicity of NC-6300 and epirubicin
was assessed by echocardiography. Neurotoxicity of NC-4016 and oxaliplatin was
evaluated by examining the paw withdrawal response to noxious mechanical stimuli.
NCs showed a highly synergistic activity equivalent to E/O. In vivo, NCs
exhibited higher antitumor activity in the subcutaneous tumor model and longer
overall survival in the orthotopic tumor model than E/O (p < 0.001, p = 0.015,
respectively). The intratumor concentrations of epirubicin and platinum were
significantly higher following NCs than following E/O administration. Moreover,
the micelles showed lower cardiotoxicity and neurotoxicity than the corresponding
conventional drugs. The combined use of the micelles was associated with
remarkable efficacy and favorable toxicities in the human gastric cancer model,
and warrants the conduct of clinical trials.
PMID- 24353133
TI - Interpretation and deconvolution of nanodisc native mass spectra.
AB - Nanodiscs are a promising system for studying gas-phase and solution complexes of
membrane proteins and lipids. We previously demonstrated that native electrospray
ionization allows mass spectral analysis of intact Nanodisc complexes at single
lipid resolution. This report details an improved theoretical framework for
interpreting and deconvoluting native mass spectra of Nanodisc lipoprotein
complexes. In addition to the intrinsic lipid count and charge distributions,
Nanodisc mass spectra are significantly shaped by constructive overlap of
adjacent charge states at integer multiples of the lipid mass. We describe the
mathematical basis for this effect and develop a probability-based algorithm to
deconvolute the underlying mass and charge distributions. The probability-based
deconvolution algorithm is applied to a series of dimyristoylphosphatidylcholine
Nanodisc native mass spectra and used to provide a quantitative picture of the
lipid loss in gas-phase fragmentation.
PMID- 24353134
TI - Quick test of ultrasonic transducer arrays radiating in air using B-mode-images.
AB - This paper describes a statistical procedure working on ultrasound B-mode images
that were recorded with the transducer array radiating in air. From the digital
image data, a gray value profile was generated using a computer program. A
statistical procedure was developed to examine if there are significant
deviations from the mean. They occur, for example, when single piezoelements are
severely damaged or completely out of function. The entire technique was tested
using an ultrasonic imaging system (SonixTouch, Ultrasonix Medical Corporation,
Richmond, Canada) in which individual elements or groups of elements can be
turned off via firmware. A failure of as large as two out of 128 elements was
detectable.
PMID- 24353135
TI - Diseases accompanying congenital hypothyroidism.
AB - INTRODUCTION: Extrathyroidal abnormality incidence and especially the incidence
of congenital cardiac disease are increased with congenital hypothyroidism. In
this present study, it is aimed to evaluate patients who were being followed up
for congenital hypothyroidism for accompanying diseases, and to compare impacts
of accompanying diseases on prognosis under the light of published articles in
the literature. MATERIAL AND METHODS: A total of 400 cases which were diagnosed
with, treated and followed up for congenital hypothyroidism in our clinic were
retrospectively evaluated. Cases with complaining symptoms and without any
complaints, but were diagnosed with hypothyroidism as the result of screening
tests were enrolled in the study. RESULTS: Of 400 subjects included due to
congenital hypothyroidism, 186 (46.5%) were girls and 214 (53.5%) were boys.
Accompanying diseases were diagnosed in 113 cases (28.2%). Accompanying diseases
according to the frequency order were congenital cardiac disease (n=32, 8.0%),
Down syndrome (n=25, 6.3%), inguinal hernia (n=21, 5.30%), undescended testicles
(n=8, 2.0%), GH deficiency (n=4, 1.0%), and some other systemic diseases (n=23,
5.8%). In cases accompanied by congenital cardiac diseases, ventricular septal
defect (n=10), atrial septal defect (n=9), pulmonary stenosis (n=7), patent
ductus arteriosis (n=7), and aortic coarctation (n=3) were detected. CONCLUSION:
In this present study, it was defined that approximately one third of patients
with congenital hypothyroidism had an accompanying disease, and cardiac diseases
were the most common problem. It is concluded that evaluation of congenital
hypothyroidism cases for accompanying diseases, detailed cardiological
examination being in the first order, is important for prognosis.
PMID- 24353136
TI - Molecular diagnosis of a Chinese pedigree with alpha-mannosidosis and
identification of a novel missense mutation.
AB - alpha-Mannosidosis storage disease is a rare autosomal recessive disease that is
caused by a deficiency of the lysosomal enzyme alpha-mannosidase. In this
article, a proband in China was preliminarily diagnosed as having alpha
mannosidosis by clinical symptoms, imaging examination, and enzyme assay.
Definitive diagnosis was performed by directly sequencing the MAN2B1 gDNA and
cDNA of the peripheral blood leukocyte from the patient. Finally, denaturing high
performance liquid chromatography screening, conservative analysis, and protein
secondary structure prediction were used to identify the novel mutation. The
results showed that the patient has compound heterozygous mutations in the MAN2B1
gene, c.856G>A (p.E286K, novel) and c.788C>T (p.P263L). Her parents are
heterozygote that carry one of these two mutations respectively. Pathogenicity
identification of the novel mutation showed that the p.E286K mutation is a
disease-causing mutation. Our work enriches the human MAN2B1 gene mutation
database. As far as we know, this research is thus far the first gene diagnosis
case of a Chinese patient with alpha-mannosidosis.
PMID- 24353137
TI - Unsaturated fatty acids and insulin resistance in childhood obesity.
AB - OBJECTIVE: Obesity is characterized by increased levels of plasma free fatty
acids (FFAs) that interfere with insulin signaling. The aim of our study was to
assess the FFA profile in obese children and adolescents and to determine their
relation with different degrees of insulin resistance. METHODS: A transversal
study was conducted of 51 children and adolescents (mean age, 11.7+/-1.6 years;
47% males) with obesity (body mass index >=95 percentile). Anthropometric,
clinical, and biochemical parameters were assessed. Insulin resistance was
determined using the homeostasis model assessment of insulin resistance (HOMA-IR)
index. Plasma fatty acids were quantified by high-performance liquid
chromatography with heptadecanoic acid as the internal standard. RESULTS: The
mean concentration of myristic acid, linoleic acid, palmitic acid, oleic acid,
stearic acid, and total fatty acids was 9.3+/-2.2, 86.5+/-38.3, 93.0+/-35.5,
177.0+/-83.6, 48.5+/-14.9, and 414.3+/-160.9 MUmol/L, respectively. Total fatty
acids and unsaturated fatty acids such as oleic acid and linoleic acid showed an
inverse significant correlation with insulin resistance. Children with high
insulin resistance (HOMA-IR >2.5) showed a decrease in unsaturated fatty acids
compared with children having a HOMA-IR of <2.5. There were no changes in
saturated fatty acid concentrations between those groups. CONCLUSIONS: A decrease
in unsaturated fatty acids was correlated with insulin resistance in childhood
obesity.
PMID- 24353138
TI - Are the characteristics of thyroid cancer different in young patients?
AB - BACKGROUND: Thyroid carcinoma in pediatric patients continues to be a rare albeit
significant condition because local recurrence or distant metastases may be
revealed during its diagnosis, or even years after completion of treatment.
METHODS: This study was prepared by retrospective analysis of patient files to
focus on the clinical presentation of thyroid carcinoma in pediatric patients,
and proposes to investigate the clinical parameters that differ from, or that
correspond to, those in adult patients. SUBJECTS: A total of 108 patients, of
whom 22 were children and adolescents and 86 were adults, and who were operated
on for differentiated thyroid carcinoma during the period 2001-2009, were
included in the study. RESULTS: The rate of large thyroid, multinodular goiter,
or tumor >1 cm was significantly higher in the adult group than in the pediatric
group. Our analysis also revealed that that the frequency of lymph node
metastasis was significantly higher in the pediatric group than in the adult
group. Moreover, the frequencies of total lymph node and positive lymph node
presentations were significantly higher in the pediatric group than in the adult
group. CONCLUSION: Although thyroid carcinoma has a good prognosis in young
patients, one must stress that late diagnosis and ineffective treatment are the
main criteria for poor prognosis and, most important, that it is advisable to
keep the management of thyroid carcinoma on a path that differs from the
management of adult thyroid carcinomas, in nearly all aspects from presentation
to treatment.
PMID- 24353140
TI - Association of diet and anthropometric measures as cardiovascular modifiable risk
factors in young adults.
AB - Abstract Background: Cardiovascular accidents are the major cause of death in the
developing world, accounting for nearly 40% of deaths in adult men and women.
Developed countries have already brought this under control, whereas India has to
take a giant leap. Diet plays a pivotal role among the various modifiable
cardiovascular risk factors. The sole objective of this study is to point at
nutrition as being the main modulator of different anthropometric parameters and
directly or indirectly has a tremendous impact on the blood pressure levels even
during young age. Methods: In a cross-sectional study involving 223 young adults,
the pattern of food habits and level of physical activity were determined from
self-reported questionnaires, while blood pressure, weight, height, waist
circumference (WC), and hip circumference were measured, and body mass index
(BMI) and waist-to-hip ratio (WHR) were computed. The subjects were grouped as
normotensives and prehypertensives and also were compared according to their BMI
and other parameters. Results: Statistically significant, greater association of
weight followed by WC with the prehypertensive levels of blood pressure compared
to other parameters was seen. The subjects detected as prehypertensives had
predilection for salty, fried, oily, sweet, and fast food; BMI >25 kg/m2; and WC
and WHR in high risk-categories per World Health Organization standards. More
than 69% of subjects had high WHR, whereas only 9% of total subjects exercised
regularly. Conclusions: Central obesity is associated with sedentary life and
high intake of calories, leading to hypertension with advancing age. Early
detection, awareness, and primary prevention would help reduce morbidity and
mortality associated with cardiovascular diseases.
PMID- 24353139
TI - Aphrodisiac effect of aqueous root extract of Lecaniodiscus cupanioides in
sexually impaired rats.
AB - BACKGROUND: The phytochemical constituents of the aqueous root extract of
Lecaniodiscus cupanioides Planch. Ex Bth. and its aphrodisiac activity on male
rat sexual behavior and reproductive hormones in paroxetine-induced sexual
dysfunction were evaluated. METHODS: The extract was screened for the presence of
phytochemicals. The extract (25, 50, and 100 mg/kg body weight) and the reference
herbal drug PowmaxM (7.14 mg/kg body weight) were administered orally to
paroxetine-induced sexually impaired male rats, once daily for 5 days, and their
sexual behavior parameters were monitored and computed. The serum hormones
(testosterone, follicle-stimulating hormone, and luteinizing hormone) were
determined at the end of treatment period. RESULTS: Phytochemical screening
revealed the presence of alkaloids, anthraquinones, phenolics, saponins, and
tannins. Mount frequency (MF), intromission frequency (IF), ejaculatory frequency
(EF), and testosterone, follicle-stimulating hormone, and luteinizing hormone
concentrations were reduced significantly (p<0.05) in paroxetine-treated rats.
Administration of 25, 50, and 100 mg/kg body weight of the aqueous root extract
of L. cupanioides significantly (p<0.05) reversed the paroxetine-mediated
alterations in MF, IF, EF, mount latency (ML), intromission latency (IL),
ejaculatory latency (EL), postejaculatory interval (PEI), and testosterone,
follicle-stimulating hormone, and luteinizing hormone concentrations dose
dependently. The reversal of the male sexual behavior parameters by the extract
compared well (p<0.05) with the PowmaxM-treated animals. CONCLUSIONS: Data
obtained from this study revealed that the aqueous root extract of L. cupanioides
restored sexual competence in sexually impaired rats possibly by increasing
sexual drive through enhanced reproductive hormones concentration, particularly
testosterone, thus supporting the folkloric claim of the plant for the management
of sexual disorder in males.
PMID- 24353141
TI - Toxicological evaluation of the lyophilized fruit juice extract of Annona
muricata Linn. (Annonaceae) in rodents.
AB - Abstract Background: Annona muricata Linn. (Annonaceae) (AM) fruit juice is
widely consumed either raw or after processing in tropical countries because of
its very juicy, creamy and sweet character including its medicinal importance.
The safety of AM fruit was investigated in Sprague-Dawley rats for acute and 60
day subchronic toxicity effects. Methods: Rats were administered distilled water
(DW) and AM daily at doses of 80, 400 and 2000 mg/kg orally for 60 days. At the
end of the study, blood samples were assayed for biochemical and hematological
parameters. Vital organs were harvested and assessed for antioxidants and
histopathology. Results: There was no mortality recorded up to 2000 mg/kg
following acute administration. There were no significant changes in vital organ
weights and hematological and biochemical parameters. However, significant
(p<0.05) reduction in platelet count and packed cell volume was observed at 2000
and 400 mg/kg, respectively, which was reversed after cessation of treatment.
Interestingly, subchronic oral administration of AM (80, 400 or 2000 mg/kg)
significantly (p<0.001) increased sperm count and motility in comparison to
vehicle-treated control. AM long-term treatment induced significant (p<0.05,
<0.01 and <0.001) increases in the levels of glutathione, superoxide dismutase
(SOD) and catalase, respectively, in the liver and kidney. Conversely, AM (2000
mg/kg) produced significant (p<0.001) increase in malondialdehyde level with
decreased (p<0.05) SOD activity in the brain. Conclusions: The study established
that AM did not induce any significant toxic effect, indicating that it is safe
in rats following oral administration for 60 consecutive days.
PMID- 24353142
TI - Reshaping biological membranes in endocytosis: crossing the configurational space
of membrane-protein interactions.
AB - Lipid membranes are highly dynamic. Over several decades, physicists and
biologists have uncovered a number of ways they can change the shape of membranes
or alter their phase behavior. In cells, the intricate action of membrane
proteins drives these processes. Considering the highly complex ways proteins
interact with biological membranes, molecular mechanisms of membrane remodeling
still remain unclear. When studying membrane remodeling phenomena, researchers
often observe different results, leading them to disparate conclusions on the
physiological course of such processes. Here we discuss how combining research
methodologies and various experimental conditions contributes to the
understanding of the entire phase space of membrane-protein interactions. Using
the example of clathrin-mediated endocytosis we try to distinguish the question
'how can proteins remodel the membrane?' from 'how do proteins remodel the
membrane in the cell?' In particular, we consider how altering physical
parameters may affect the way membrane is remodeled. Uncovering the full range of
physical conditions under which membrane phenomena take place is key in
understanding the way cells take advantage of membrane properties in carrying out
their vital tasks.
PMID- 24353143
TI - Non-invasive detection of fetal trisomy 21 using fetal epigenetic biomarkers with
a high CpG density.
AB - BACKGROUND: Non-invasive prenatal test of trisomy 21 (T21) is being researched
using fetal specific epigenetic biomarkers present in maternal plasma. We applied
a methyl-CpG binding domain-based protein (MBD) method based on epigenetic
characteristics of fetal specific-methylated regions with a high CpG density in
HLCS on chromosome 21 and RASSF1A on chromosome 3 for the non-invasive detection
of fetal T21 and estimated the diagnostic accuracy of the method. METHODS: A
nested case-control study was conducted with maternal plasma collected from 50
pregnant women carrying 40 normal and 10 T21 fetuses. A MBD method was used for
enrichment of methylated DNA regions in maternal plasma. The levels of methylated
HLCS (M-HLCS) and methylated RASSF1A (M-RASSF1A) were simultaneously measured by
multiplex qPCR. RESULTS: Levels of M-HLCS and M-RASSF1A were obtained in all
cases. Levels were not different according to fetal gender (p>0.05 in both). The
level of M-HLCS was significantly increased in women with a T21 fetus compared
with controls (p<0.001). The level of M-RASSF1A was not different between two
groups (p>0.05). In non-invasive fetal T21 detection, the specificity of M-HLCS
level and the epigenetic-epigenetic ratio (EER) using M-HLCS and M-RASSF1A levels
were 82.5% and 92.5%, respectively, at 90.0% sensitivity. CONCLUSIONS: Our
findings suggest that the EER may be useful as a potential biomarker for the non
invasive detection of fetal T21, regardless of fetal gender. The MBD method can
be used as an effective tool in the detection of methylated fetal specific
markers with a high CpG density in maternal plasma.
PMID- 24353144
TI - Do we need to worry about contamination by circulating fetal DNA?
PMID- 24353145
TI - Epigenetic mechanisms in bone.
AB - Epigenetics refers to the study of mechanisms able to influence gene expression
in a stable and potentially heritable manner without altering the DNA sequence.
These mechanisms include posttranslational histone modifications, miRNA-mediated
post-transcriptional regulation and DNA methylation. The accumulation of
molecular errors over time resulting, at least partly, in the alteration of
normal epigenetic patterns is being widely associated with aging. Epigenetic
processes are also considered important mechanisms through which environmental
and stochastic stressors promote numerous pathologies in humans. It is,
therefore, reasonable to expect that several complex multi-factorial late-onset
disorders, like osteoporosis and osteoarthritis, could have a strong epigenetic
component. The focal point of all skeletal pathologies is the deregulation of
bone remodeling, mediated by bone-forming osteoblasts and bone-resorbing
osteoclasts. In order to keep both processes in balance, the activity,
differentiation and apoptosis of both cell types have to be tightly regulated. In
particular, the differentiation of osteoblasts and osteoclasts is accompanied by
profound changes in gene expression. It has been shown that histone deacetylation
and DNA methylation negatively regulate the expression of several genes
associated with different stages of osteoblast differentiation; however, several
miRNAs promote osteoblastogenesis. Furthermore, inactivating mutations in the
miRNA coding regions could be associated with the pathogenesis of osteoporosis.
The aim of this review is to highlight the role of epigenetic mechanisms in bone
remodeling and bone homeostasis, so as to implicate their diagnostic and
therapeutic potential in skeletal diseases.
PMID- 24353146
TI - Performance characteristics of ultrasound-guided fine-needle aspiration of
axillary lymph nodes for metastatic breast cancer employing rapid on-site
evaluation of adequacy: analysis of 136 cases and review of the literature.
AB - BACKGROUND: It has been demonstrated that axillary ultrasound-guided fine-needle
aspiration (US-FNA) has excellent positive predictive value for the axillary
lymph node status of patients with breast cancer before surgery or neoadjuvant
therapy and, thus, can obviate the need for sentinel lymph node biopsy in FNA
positive patients. However, US-FNA has only moderate sensitivity, in part because
of the collection of nondiagnostic or equivocal specimens. Rapid on-site
evaluation for adequacy (ROSE) can improve definitive diagnosis rates but has not
been well characterized in this setting. METHODS: One hundred thirty-three
patients with breast carcinoma were identified who underwent 136 US-FNAs of
axillary lymph nodes, all with ROSE, and the results were correlated with the
diagnosis on a subsequent surgical procedure. RESULTS: The adequacy rate was
95.6% (130 of 136 FNAs), and a definitive diagnosis was made in 91.2% (124 of 136
FNAs). Among definite diagnoses, sensitivity was 75%, specificity was 100%, the
positive predictive value was 100%, and the negative predictive value was 79%.
Sources of false-negative and potential false-positive diagnoses were evaluated
among these cases and in the literature. CONCLUSIONS: Small metastasis size is
the most common cause of false-negative results, whereas interpretation errors by
pathologists are quite rare. ROSE appears to improve adequacy and definitive
diagnosis rates and, thus, can more accurately triage patients to appropriate
care.
PMID- 24353147
TI - Prey switching as a means of enhancing persistence in predators at the trailing
southern edge.
AB - Understanding the effects of climate change on species' persistence is a major
research interest; however, most studies have focused on responses at the
northern or expanding range edge. There is a pressing need to explain how species
can persist at their southern range when changing biotic interactions will
influence species occurrence. For predators, variation in distribution of primary
prey owing to climate change will lead to mismatched distribution and local
extinction, unless their diet is altered to more extensively include alternate
prey. We assessed whether addition of prey information in climate projections
restricted projected habitat of a specialist predator, Canada lynx (Lynx
canadensis), and if switching from their primary prey (snowshoe hare; Lepus
americanus) to an alternate prey (red squirrel; Tamiasciurus hudsonicus)
mitigates range restriction along the southern range edge. Our models projected
distributions of each species to 2050 and 2080 to then refine predictions for
southern lynx on the basis of varying combinations of prey availability. We found
that models that incorporated information on prey substantially reduced the total
predicted southern range of lynx in both 2050 and 2080. However, models that
emphasized red squirrel as the primary species had 7-24% lower southern range
loss than the corresponding snowshoe hare model. These results illustrate that
(i) persistence at the southern range may require species to exploit higher
portions of alternate food; (ii) selection may act on marginal populations to
accommodate phenotypic changes that will allow increased use of alternate
resources; and (iii) climate projections based solely on abiotic data can
underestimate the severity of future range restriction. In the case of Canada
lynx, our results indicate that the southern range likely will be characterized
by locally varying levels of mismatch with prey such that the extent of range
recession or local adaptation may appear as a geographical mosaic.
PMID- 24353148
TI - Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI:
image reconstruction, biological half-lives and sensitivity.
AB - Inflammatory processes can reliably be assessed by (19)F MRI using
perfluorocarbons (PFCs), which is primarily based on the efficient uptake of
emulsified PFCs by circulating cells of the monocyte-macrophage system and
subsequent infiltration of the (19)F-labeled cells into affected tissue. An ideal
candidate for the sensitive detection of fluorine-loaded cells is the
biochemically inert perfluoro-15-crown-5 ether (PFCE), as it contains 20
magnetically equivalent (19)F atoms. However, the biological half-life of PFCE in
the liver and spleen is extremely long, and so this substance is not suitable for
future clinical applications. In the present study, we investigated alternative,
nontoxic PFCs with predicted short biological half-lives and high fluorine
content: perfluorooctyl bromide (PFOB), perfluorodecalin (PFD) and trans-bis
perfluorobutyl ethylene (F-44E). Despite the complex spectra of these compounds,
we obtained artifact-free images using sine-squared acquisition-weighted three
dimensional chemical shift imaging and dedicated reconstruction accomplished with
in-house-developed software. The signal-to-noise ratio of the images was
maximized using a Nutall window with only moderate localization error. Using this
approach, the retention times of the different PFCs in murine liver and spleen
were determined at 9.4 T. The biological half-lives were estimated to be 9 days
(PFD), 12 days (PFOB) and 28 days (F-44E), compared with more than 250 days for
PFCE. In vivo sensitivity for inflammation imaging was assessed using an ear clip
injury model. The alternative PFCs PFOB and F-44E provided 37% and 43%,
respectively, of the PFCE intensities, whereas PFD did not show any signal in the
ear model. Thus, for in vivo monitoring of inflammatory processes, PFOB emerges
as the most promising candidate for possible future translation of (19)F MR
inflammation imaging to human applications.
PMID- 24353149
TI - Conditionally unbiased and near unbiased estimation of the selected treatment
mean for multistage drop-the-losers trials.
AB - The two-stage drop-the-loser design provides a framework for selecting the most
promising of K experimental treatments in stage one, in order to test it against
a control in a confirmatory analysis at stage two. The multistage drop-the-losers
design is both a natural extension of the original two-stage design, and a
special case of the more general framework of Stallard & Friede () (Stat. Med.
27, 6209-6227). It may be a useful strategy if deselecting all but the best
performing treatment after one interim analysis is thought to pose an
unacceptable risk of dropping the truly best treatment. However, estimation has
yet to be considered for this design. Building on the work of Cohen & Sackrowitz
() (Stat. Prob. Lett. 8, 273-278), we derive unbiased and near-unbiased estimates
in the multistage setting. Complications caused by the multistage selection
process are shown to hinder a simple identification of the multistage uniform
minimum variance conditionally unbiased estimate (UMVCUE); two separate but
related estimators are therefore proposed, each containing some of the UMVCUEs
theoretical characteristics. For a specific example of a three-stage drop-the
losers trial, we compare their performance against several alternative estimators
in terms of bias, mean squared error, confidence interval width and coverage.
PMID- 24353150
TI - [Sport in the winter -- excuses do not count!].
PMID- 24353151
TI - [Overuse injuries in sports -- how to prevent them in children?].
PMID- 24353152
TI - [Basic knowledge on concussion in the German Ice Hockey League (DEL)].
AB - OBJECTIVE: In professional ice hockey there is a high incidence of concussion. In
order to implement preventative measures as well as to introduce a treatment
concept it is necessary to analyse the basic knowledge about concussion of all
participants and to identify aspects requiring additional educational measures.
METHOD: By means of an internet-based questionnaire comprising 18 questions,
trainers and co-trainers, sport directors, team physicians and team captains of
all teams in the German ice hockey league were interviewed about their knowledge
and impressions with regard to general knowledge, game-stop, protection, and
training as well as their opinions about changing the penalty system. RESULTS:
The response rate amounted to 57.8 %. Not only team physicians but also players,
trainers and sport directors exhibited a good basic knowledge on concussion,
duration of treatment and rehabilitation as well as possible long-term sequelae.
There were only slight differences in knowledge between team physicians and not
medically trained personnel. This survey also revealed a broad support for
educational measures about concussion and the possibility for rule changes to
further protect the players. CONCLUSION: There appears to be an acceptable basic
knowledge about concussion and its symptoms and no major underestimation of the
problems. All participants were in favour of the provision of further information
as well as the implementation of preventative measures.
PMID- 24353153
TI - [Proximal tibial fractures sustained during alpine skiing - incidence and risk
factors].
AB - BACKGROUND: Prior to introduction of carving skis, complex fractures of the
proximal tibia were rarely seen. Recently these fractures are being seen more
frequently in connection with alpine skiing. The aim of this study was to find
out the incidence of proximal tibia fractures in alpine skiing and to identify
possible risk factors. METHODS: All patients with proximal tibia fractures
related to alpine skiing in a large German ski resort were included. Fracture
type, patient and skiing related factors were recorded. Incidence of fractures
was determined by using the number of all registered skiers. Multinomial logistic
regression analysis was used to calculate the odds ratios for risk factors.
RESULTS: Between 2007 and 2010 a total of 188 patients was treated for proximal
tibia fractures caused by alpine skiing. Forty-three patients had a type-A
injury, 96 patients a type-B injury, and 49 patients a type-C injury. The
incidence of injury increased continuously, starting from 2.7 and climbing to 7.0
per 105 skiing days. The risk factors compared to patients with type-A fractures,
type-C fracture occurred in older (OR 0.93; 0.89 - 0.97) and heavier (OR 0.86;
0.74 - 0.99) individuals and were more likely on icy snow conditions (OR 0.22;
0.05 - 0.96), higher speed (OR 0.29; 0.09 - 0.97) and skiing skill (OR 0.35; 0.13
- 0.95). These was also seen in artificial and icy snow conditions (OR 0.25; 0.07
- 0.87) when compared to type-B fractures. CONCLUSION: The incidence of proximal
tibia fractures related to skiing has increased over the past four years. Risk
factors such as age, BMI, snow conditions, speed, and the skill of the skiers,
were identified as causes contributing to complex fractures.
PMID- 24353154
TI - [The relevance of core muscles in ice hockey players: a feasibility study].
AB - BACKGROUND: Good core strength is seen as a condition for high performance in
sports. In general, especially maximum voluntary contraction (MVC) and strength
endurance (SE) measurements of the core muscles are used. In addition, a few
studies can be found that examine the core muscles in terms of MVC, rate of force
development (RFD) and SE. Primary aims of this feasibility study were to
investigate the feasibility regarding recruiting process, compliance and safety
of the testing conditions and raise the force capabilities MVC, RFD and SE of the
core muscles in amateur ice hockey players. Secondarily, tendencies of
correlations between muscle activity and either shot speed and sprint time shall
be examined. SUBJECTS/METHODS: In this feasibility study the recruitment process
has been approved by 29 ice hockey players, their adherence to the study
measurements of trunk muscles, and safety of the measurements was evaluated. To
determine the MVC, RFD and SE for the ventral, lateral and dorsal core muscles a
dynamic force measurement was performed. To determine the correlation between
core muscles and shot speed and 40-m sprint, respectively, the rank correlation
coefficient (rho) from Spearman was used. RESULTS: The recruited number of eight
field players and one goal-keeper was not very high. The compliance with 100 %
was excellent. The players reported no adverse symptoms or injuries after the
measurements. The results show median values for the ventral core muscles for MVC
with 46.5 kg for RFD with 2.23 m/s2 and 96 s for the SE. For lateral core muscle
median values of the lateral core muscles for MVC with 71.10 kg, RFD with 2.59
m/s2 and for SE over 66 s were determined. The dorsal core muscles shows values
for MVC 69.7 kg, for RFD 3.39 m/s2 and for SE of 75 s. High correlations between
MVC of the ventral core muscles (rho = -0.721, p = 0.021), and between the SE of
the ventral core muscles (rho = 0.787, p = 0.012), and the shot velocity rate
were determined. Another high correlation between SE of the ventral core muscles
and sprint over 40 m (rho = 0.717, p = 0.030) could be demonstrated. CONCLUSION:
This feasibility study has shown that the implementation of the selected design
is adapted for future studies. Further studies are needed to better understand
the relationship between the velocity rate and the MVC, and the SE respectively,
as well as between the sprint and the SE.
PMID- 24353155
TI - Local versus general anaesthesia for carotid endarterectomy.
AB - BACKGROUND: Carotid endarterectomy may significantly reduce the risk of stroke in
people with recently symptomatic, severe carotid artery stenosis. However, there
are significant perioperative risks that may be reduced by performing the
operation under local rather than general anaesthetic. This is an update of a
Cochrane Review first published in 1996, and previously updated in 2004 and 2008.
OBJECTIVES: To determine whether carotid endarterectomy under local anaesthetic:
(1) reduces the risk of perioperative stroke and death compared with general
anaesthetic; (2) reduces the complication rate (other than stroke) following
carotid endarterectomy; and (3) is acceptable to patients and surgeons. SEARCH
METHODS: We searched the Cochrane Stroke Group Trials Register (September 2013),
MEDLINE (1966 to September 2013), EMBASE (1980 to September 2013) and Index to
Scientific and Technical Proceedings (ISTP) (1980 to September 2013). We also
handsearched relevant journals, and searched the reference lists of articles
identified. SELECTION CRITERIA: Randomised trials comparing the use of local
anaesthetic to general anaesthetic for carotid endarterectomy were considered for
inclusion. DATA COLLECTION AND ANALYSIS: Three review authors independently
assessed trial quality and extracted data. We calculated a pooled Peto odds ratio
(OR) and corresponding 95% confidence interval (CI) for the following outcomes
that occurred within 30 days of surgery: stroke, death, stroke or death,
myocardial infarction, local haemorrhage, cranial nerve injuries, and shunted
arteries. MAIN RESULTS: We included 14 randomised trials involving 4596
operations, of which 3526 were from the single largest trial (GALA). In general,
reporting of methodology in the included studies was poor. All studies were
unable to blind patients and surgical teams to randomised treatment allocation
and for most studies the blinding of outcome assessors was unclear. There was no
statistically significant difference in the incidence of stroke within 30 days of
surgery between the local anaesthesia group and the general anaesthesia group.
The incidence of strokes in the local anaesthesia group was 3.2% compared to 3.5%
in the general anaesthesia group (Peto OR 0.92, 95% CI 0.67 to 1.28). There was
no statistically significant difference in the proportion of patients who had a
stroke or died within 30 days of surgery. In the local anaesthesia group 3.6% of
patients had a stroke or died compared to 4.2% of patients in the general
anaesthesia group (Peto OR 0.85, 95% CI 0.63 to 1.16). There was a non
significant trend towards lower operative mortality with local anaesthetic. In
the local anaesthesia group 0.9% of patients died within 30 days of surgery
compared to 1.5% of patients in the general anaesthesia group (Peto OR 0.62, 95%
CI 0.36 to 1.07). However, neither the GALA trial or the pooled analysis were
adequately powered to reliably detect an effect on mortality. AUTHORS'
CONCLUSIONS: The proportion of patients who had a stroke or died within 30 days
of surgery did not differ significantly between the two types of anaesthetic
techniques used during carotid endarterectomy. This systematic review provides
evidence to suggest that patients and surgeons can choose either anaesthetic
technique, depending on the clinical situation and their own preferences.
PMID- 24353156
TI - Escalating criminal and civil violations: pharma has corporate integrity? Not
really.
PMID- 24353157
TI - New frontiers for collaborative research.
PMID- 24353158
TI - Allelic-dependent expression of an activating Fc receptor on B cells enhances
humoral immune responses.
AB - B cells are pivotal regulators of acquired immune responses, and recent work in
both experimental murine models and humans has demonstrated that subtle changes
in the regulation of B cell function can substantially alter immunological
responses. The balance of negative and positive signals in maintaining an
appropriate B cell activation threshold is critical in B lymphocyte immune
tolerance and autoreactivity. FcgammaRIIb (CD32B), the only recognized Fcgamma
receptor on B cells, provides immunoglobulin G (IgG)-mediated negative modulation
through a tyrosine-based inhibition motif, which down-regulates B cell receptor
initiated signaling. These properties make FcgammaRIIb a promising target for
antibody-based therapy. We report the discovery of allele-dependent expression of
the activating FcgammaRIIc on B cells. Identical to FcgammaRIIb in the
extracellular domain, FcgammaRIIc has a tyrosine-based activation motif in its
cytoplasmic domain. In both human B cells and B cells from mice transgenic for
human FcgammaRIIc, FcgammaRIIc expression counterbalances the negative feedback
of FcgammaRIIb and enhances humoral responses to immunization in mice and to
BioThrax vaccination in a human anthrax vaccine trial. Moreover, the FCGR2C-ORF
allele is associated with the risk of development of autoimmunity in humans.
FcgammaRIIc expression on B cells challenges the prevailing paradigm of
unidirectional negative feedback by IgG immune complexes via the inhibitory
FcgammaRIIb, is a previously unrecognized determinant in human
antibody/autoantibody responses, and opens the opportunity for more precise
personalized use of B cell-targeted antibody-based therapy.
PMID- 24353159
TI - CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1
influenza A epitope in narcolepsy.
AB - Narcolepsy, a disorder strongly associated with human leukocyte antigen (HLA)
DQA1*01:02/DQB1*06:02 (DQ0602), is characterized by excessive daytime sleepiness,
cataplexy, and rapid eye movement sleep abnormalities. It is caused by the loss
of ~70,000 posterior hypothalamic neurons that produce the wake-promoting
neuropeptide hypocretin (HCRT) (orexin). We identified two DQ0602-binding HCRT
epitopes, HCRT56-68 and HCRT87-99, that activated a subpopulation of CD4(+) T
cells in narcolepsy patients but not in DQ0602-positive healthy control subjects.
Because of the established association of narcolepsy with the 2009 H1N1 influenza
A strain (pH1N1), we administered a seasonal influenza vaccine (containing pH1N1)
to patients with narcolepsy and found an increased frequency of circulating
HCRT56-68- and HCRT87-99-reactive T cells. We also identified a hemagglutinin
(HA) pHA1 epitope specific to the 2009 H1N1 strain, pHA1275-287, with homology to
HCRT56-68 and HCRT87-99. In vitro stimulation of narcolepsy CD4(+) T cells with
pH1N1 proteins or pHA1275-287 increased the frequency of HCRT56-68- and HCRT87-99
reactive T cells. Our data indicate the presence of CD4(+) T cells that are
reactive to HCRT in narcolepsy patients and possible molecular mimicry between
HCRT and a similar epitope in influenza pH1N1, pHA1275-287.
PMID- 24353161
TI - Cancer nanomedicine: from drug delivery to imaging.
AB - Nanotechnology-based chemotherapeutics and imaging agents represent a new era of
"cancer nanomedicine" working to deliver versatile payloads with favorable
pharmacokinetics and capitalize on molecular and cellular targeting for enhanced
specificity, efficacy, and safety. Despite the versatility of many nanomedicine
based platforms, translating new drug or imaging agents to the clinic is costly
and often hampered by regulatory hurdles. Therefore, translating cancer
nanomedicine may largely be application-defined, where materials are adapted only
toward specific indications where their properties confer unique advantages. This
strategy may also realize therapies that can optimize clinical impact through
combinatorial nanomedicine. In this review, we discuss how particular materials
lend themselves to specific applications, the progress to date in clinical
translation of nanomedicine, and promising approaches that may catalyze clinical
acceptance of nano.
PMID- 24353160
TI - Structural, biochemical, and clinical characterization of epidermal growth factor
receptor (EGFR) exon 20 insertion mutations in lung cancer.
AB - Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19
deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR
tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC).
However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are
generally associated with insensitivity to available TKIs (gefitinib, erlotinib,
and afatinib). The basis of this primary resistance is poorly understood. We
studied a broad subset of exon 20 insertion mutations, comparing in vitro TKI
sensitivity with responses to gefitinib and erlotinib in NSCLC patients, and
found that most are resistant to EGFR TKIs. The crystal structure of a
representative TKI-insensitive mutant (D770_N771insNPG) reveals an unaltered
adenosine triphosphate-binding pocket, and the inserted residues form a wedge at
the end of the C helix that promotes the active kinase conformation. Unlike EGFR
L858R, D770_N771insNPG activates EGFR without increasing its affinity for EGFR
TKIs. Unexpectedly, we find that EGFR-A763_Y764insFQEA is highly sensitive to
EGFR TKIs in vitro, and patients whose NSCLCs harbor this mutation respond to
erlotinib. Analysis of the A763_Y764insFQEA mutant indicates that the inserted
residues shift the register of the C helix in the N-terminal direction, altering
the structure in the region that is also affected by the TKI-sensitive EGFR
L858R. Our studies reveal intricate differences between EGFR mutations, their
biology, and their response to EGFR TKIs.
PMID- 24353163
TI - Anticholinergic medication for non-clozapine neuroleptic-induced hypersalivation
in people with schizophrenia.
AB - BACKGROUND: Treatment of schizophrenia depends heavily on neuroleptic drugs.
Hypersalivation is a common side effect when people with schizophrenia are
treated with neuroleptic drugs. Hypersalivation can be an embarrassing and
stigmatising problem, can affect quality of life and can result in
discontinuation of neuroleptic treatment. It can also be difficult to treat.
OBJECTIVES: To summarise the best available evidence of the effects of
anticholinergic drugs in the treatment of non-clozapine neuroleptic-induced
hypersalivation in people with schizophrenia. Clozapine-induced hypersalivation
has been addressed in another Cochrane review. SEARCH METHODS: We searched the
Cochrane Schizophrenia Group Trials Register (15 November 2012) and inspected
references of all identified studies for further relevant studies. We were to
contact the first author of each included study for information regarding
unpublished trials. SELECTION CRITERIA: All randomised controlled trials
comparing an anticholinergic drug with placebo, no treatment, another
anticholinergic drug or any other intervention. DATA COLLECTION AND ANALYSIS: We
inspected the results of the search to identify relevant studies. We were to
extract data onto standard, simple forms. Disagreements were resolved through
discussion. The risk of bias was to be assessed using the Cochrane risk
assessment tool. For binary outcomes, we were to calculate a standard estimation
of the risk ratio (RR) and its 95% confidence interval (CI). For continuous
outcomes, we were to estimate the mean difference between groups. MAIN RESULTS:
The search resulted in four potential studies; after inspection, all were
excluded. Three studies were excluded because they involved people with clozapine
induced hypersalivation - a topic covered in another Cochrane review. The fourth
study was excluded because it involved people with schizophrenia, mood disorders
or other mental disorders who were suffering from clozapine- and non-clozapine
induced hypersalivation and were treated with Chinese medicines with unknown
anticholinergic properties. People in the control group received an
anticholinergic drug (artane) or an antihistamine (phenergan). It was not
possible to separate clozapine- from non-clozapine-treated people in the
intervention group, or to separate artane-treated people from phenergan-treated
people in the control group. AUTHORS' CONCLUSIONS: We have been unable to locate
any studies addressing the question raised in this review. Accordingly, this
empty review points out an important clinical problem that needs to be
investigated via well-designed and well-conducted randomised trials. Clinicians
and patients are likely to continue with their current dependence on clinical
judgement and personal experience. Policy makers have no trial-based evidence
upon which to base guidelines for the treatment of hypersalivation induced by
neuroleptics other than clozapine. They are likely to continue to rely on opinion
and habit when making recommendations. Funders of studies may wish to make this
important subgroup of people a priority in future research.
PMID- 24353164
TI - Temporal changes in artificial light exposure of marine turtle nesting areas.
AB - Artificial light at night poses a significant threat to multiple taxa across the
globe. In coastal regions, artificial lighting close to marine turtle nesting
beaches is disruptive to their breeding success. Prioritizing effective
management of light pollution requires an understanding of how the light exposure
of nesting areas changes over time in response to changing temporal and spatial
distributions of coastal development. We analyzed multitemporal, satellite night
light data, in combination with linear mixed model analysis, to determine
broadscale changes in artificial light exposure at Australian marine turtle
nesting areas between 1993 and 2010. We found seven marine turtle management
units (MU), from five species, have experienced significant increases in light
exposure over time, with flatback turtles nesting in east Australia experiencing
the fastest increases. The remaining 12 MUs showed no significant change in light
exposure. Unchanging MUs included those previously identified as having high
exposure to light pollution (located in western Australia and southern
Queensland), indicating that turtles in these areas have been potentially exposed
to high light levels since at least the early nineties. At a finer geographic
scale (within-MU), nine MUs contained nesting areas with significant increases in
light exposure. These nesting areas predominantly occurred close to heavily
industrialized coastal areas, thus emphasizing the importance of rigorous light
management in industry. Within all MUs, nesting areas existed where light levels
were extremely low and/or had not significantly increased since 1993. With
continued coastal development, nesting females may shift to these
darker/unchanging 'buffer' areas in the future. This is valuable information that
informs our understanding of the capacity and resilience of marine turtles faced
with coastal development: an understanding that is essential for effective marine
turtle conservation.
PMID- 24353162
TI - Genetic gains and losses in oral squamous cell carcinoma: impact on clinical
management.
AB - PURPOSE: The identification of genetic markers associated with oral cancer is
considered essential to improve the diagnosis, prognosis, early tumor and relapse
detection and, ultimately, to delineate individualized therapeutic approaches.
Here, we aimed at identifying such markers. METHODS: Multiplex Ligation-dependent
Probe Amplification (MLPA) analyses encompassing 133 cancer-related genes were
performed on a panel of primary oral tumor samples and its corresponding
resection margins (macroscopically tumor-free tissue) allowing, in both types of
tissue, the detection of a wide arrange of copy number imbalances on various
human chromosomes. RESULTS: We found that in tumor tissue, from the 133 cancer
related genes included in this study, those that most frequently exhibited copy
number gains were located on chromosomal arms 3q, 6p, 8q, 11q, 16p, 16q, 17p, 17q
and 19q, whereas those most frequently exhibiting copy number losses were located
on chromosomal arms 2q, 3p, 4q, 5q, 8p, 9p, 11q and 18q. Several imbalances were
highlighted, i.e., losses of ERBB4, CTNNB1, NFKB1, IL2, IL12B, TUSC3, CDKN2A,
CASP1, and gains of MME, BCL6, VEGF, PTK2, PTP4A3, RNF139, CCND1, FGF3, CTTN,
MVP, CDH1, BRCA1, CDKN2D, BAX, as well as exon 4 of TP53. Comparisons between
tumor and matched macroscopically tumor-free tissues allowed us to build a
logistic regression model to predict the tissue type (benign versus malignant).
In this model, the TUSC3 gene showed statistical significance, indicating that
loss of this gene may serve as a good indicator of malignancy. CONCLUSIONS: Our
results point towards relevance of the above mentioned cancer-related genes as
putative genetic markers for oral cancer. For practical clinical purposes, these
genetic markers should be validated in additional studies.
PMID- 24353165
TI - Assessing the minimally verbal school-aged child with autism spectrum disorder.
AB - This paper addresses the issue of assessing communication, language, and
associated cognitive and behavioral abilities of minimally verbal children with
autism spectrum disorder (ASD), presenting a summary of a year-long series of
meetings held by a group of experts in the field of ASD and National Institutes
of Health staff. In this paper, our goals were to first define the population and
then present general guidelines for optimizing assessment sessions for this
challenging population. We then summarize the available measures that can be used
across a variety of behavioral domains that are most directly relevant to
developing language skills, including oral motor skills, vocal repertoire,
receptive and expressive language, imitation, intentional communication, play,
social behavior, repetitive and sensory behaviors, and nonverbal cognition. We
conclude with a discussion of some of the limitations in the available measures
and highlight recommendations for future research in this area.
PMID- 24353169
TI - Forgiveness, coping, and terrorism: do tendency to forgive and coping strategies
associate with the level of posttraumatic symptoms of injured victims of terror
attacks?
AB - OBJECTIVE: The study examined the tendency to forgive (self, others, and
situations) and coping strategies (problem-focused, emotion-focused, and
avoidance) among terror attack victims as associated with posttraumatic stress
disorder (PTSD) symptom severity. METHOD: The sample included 108 terror victims
who had been injured in terror attacks (mean age 46.23, standard deviation =
11.61; 58.3% male). Participants agreed to undergo assessments of their PTSD
symptoms, coping strategies, and tendency to forgive. RESULTS: A nested
structural equation model design showed that tendency to forgive is positively
associated with problem-focused coping and negatively associated with avoidance
coping. Additionally, tendency to forgive and problem-focused coping are
associated with decreased PTSD symptom severity, whereas emotion-focused coping
is associated with elevated PTSD symptom severity. CONCLUSIONS: Tendency to
forgive and coping strategies are significantly associated with each other and
with severity of PTSD symptoms among individuals injured in terror attacks.
Theoretical and clinical implications of the findings are discussed.
PMID- 24353168
TI - 1 alpha, 25-dihydroxylvitamin D3 promotes Bacillus Calmette-Guerin immunotherapy
of bladder cancer.
AB - Bacillus Calmette-Guerin (BCG), a vaccine against tuberculosis(TB), has been used
and proven to be one of the most effective treatments for non-muscle invasive
bladder cancer (BCa). However, the mechanisms of BCG action have not been
completely understood, thereby limiting the improvement of BCG therapy. Vitamin D
deficiency has been associated with a high risk of TB infection, and the
beneficial effect of UV exposure in TB patients was proven to be mediated via
activation of vitamin D signals of innate immune cells. Thus, vitamin D signals
might be involved in mediating BCG immunotherapy. To test this hypothesis, we
examined the impact of 1 alpha, 25-dihydroxyvitamin D3 (1,25-VD) on BCG-induced
response in BCa cells and macrophage cells. Our data revealed that 1,25-VD
promotes BCG-induced interleukin 8 (IL-8) secretion by BCa cells, consequently
inducing the migration of macrophage, THP-1. This THP-1 cell migration promoted
by 1,25-VD can be blocked by IL-8 neutralized antibody. Furthermore, 1,25-VD
increased BCG-induced expression of macrophage markers in THP-1 cell, and
enhanced the BCG-induced THP-1 cytotoxicity against low-grade BCa cells.
Importantly, a pre-clinical trial using the N-butyl-N-(4-hydroxybutyl)
nitrosamine (BBN)-induced BCa mouse model revealed that intravesical co-treatment
of 1,25-VD with BCG can prolong mice survival. These data demonstrate a novel
mechanism by which 1,25-VD promotes BCG-mediated anti-BCa pathways and provides a
platform for improving BCG efficacy with combination of 1,25-VD.
PMID- 24353170
TI - Intersubunit communication in the dihydroorotase-aspartate transcarbamoylase
complex of Aquifex aeolicus.
AB - Aspartate transcarbamoylase and dihydroorotase, enzymes that catalyze the second
and third step in de novo pyrimidine biosynthesis, are associated in dodecameric
complexes in Aquifex aeolicus and many other organisms. The architecture of the
dodecamer is ideally suited to channel the intermediate, carbamoyl aspartate from
its site of synthesis on the ATC subunit to the active site of DHO, which
catalyzes the next step in the pathway, because both reactions occur within a
large, internal solvent-filled cavity. Channeling usually requires that the
reactions of the enzymes are coordinated so that the rate of synthesis of the
intermediate matches its rate of utilization. The linkage between the ATC and DHO
subunits was demonstrated by showing that the binding of the bisubstrate analog,
N-phosphonacetyl-L-aspartate to the ATC subunit inhibits the activity of the
distal DHO subunit. Structural studies identified a DHO loop, loop A,
interdigitating between the ATC domains that would be expected to interfere with
domain closure essential for ATC catalysis. Mutation of the DHO residues in loop
A that penetrate deeply between the two ATC domains inhibits the ATC activity by
interfering with the normal reciprocal linkage between the two enzymes. Moreover,
a synthetic peptide that mimics that part of the DHO loop that binds between the
two ATC domains was found to be an allosteric or noncompletive ATC inhibitor
(K(i) = 22 MUM). A model is proposed suggesting that loop A is an important
component of the functional linkage between the enzymes.
PMID- 24353171
TI - A method to rationally increase protein stability based on the charge-charge
interaction, with application to lipase LipK107.
AB - We report a suite of enzyme redesign protocol based on the surface charge-charge
interaction calculation, which is potentially applied to improve the stability of
an enzyme without compromising its catalytic activity. Together with the
experimental validation, we have released a suite of enzyme redesign algorithm
Enzyme Thermal Stability System, written based on our model, for open access to
meet the needs in wet labs. Lipk107, a lipase of a versatile industrial use, was
chosen to test our software. Our calculation determined that four residues, D113,
D149, D213, and D253, located on the surface of LipK107 were critical to the
stability of the enzyme. The model was validated with mutagenesis at these four
residues followed by stability and activity tests. LipK107 mutants D113A and
D149K were more resistant to thermal inactivation with ~10 degrees C higher half
inactivation temperature than wild-type LipK107. Moreover, mutant D149K exhibited
significant retention in residual activity under constant heat, showing a 14-fold
increase in the half-inactivation time at 50 degrees C. Activity tests showed
that these mutants retained the equal or higher specific activity, among which
noteworthy was the mutant D253A with as much as 20% higher activity. We suggest
that our protocol could be used as a general guideline to redesign protein
enzymes with increased stabilities and enhanced activities.
PMID- 24353174
TI - Radiolabelled porphyrins in nuclear medicine.
AB - Amongst tumour-specific substances, hematoporphyrin and synthetic porphyrin
derivatives have been widely investigated to identify and delineate neoplastic
and malignant tissue. Whilst the tumour localization exhibited by selected
porphyrin species has been exploited through photodynamic therapy, several
examples of porphyrin derivatives with varied peripheral functionality have been
radiolabelled with the aim of developing porphyrin-based nuclear imaging and
therapeutic agents. In this review, we look at the approaches and advances in the
preparation and uses of such radiolabelled agents for imaging and therapy.
PMID- 24353175
TI - Adipose-derived mesenchymal stromal cells from aged patients with coronary artery
disease keep mesenchymal stromal cell properties but exhibit characteristics of
aging and have impaired angiogenic potential.
AB - Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal
stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete
various angiogenic factors and improve vascularization of ischemic tissues. We
analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were
isolated from subcutaneous fat tissue of patients with coronary artery disease
(CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC
phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(
)/CD31(-) for all samples, and these cells were capable of adipogenic and
osteogenic differentiation. ADSCs from aged patients had shorter telomeres
(quantitative reverse transcription polymerase chain reaction) and a tendency to
attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated
capillary-like tube formation by endothelial cells (EA.hy926), and this effect
significantly decreased with the age of patients both with and without CAD.
Angiogenic factors (vascular endothelial growth factor, placental growth factor,
hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by
enzyme-linked immunosorbent assay significantly decreased with patient age,
whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not.
Expression of angiogenic factors in ADSCs did not change with patient age (real
time polymerase chain reaction); however, gene expression of factors related to
extracellular proteolysis (urokinase and its receptor, plasminogen activator
inhibitor-1) and urokinase-type plasminogen activator receptor surface expression
increased in ADSCs from aged patients with CAD. ADSCs from aged patients both
with and without CAD acquire aging characteristics, and their angiogenic
potential declines because of decreasing proangiogenic factor secretion. This
could restrict the effectiveness of autologous cell therapy with ADSCs in aged
patients.
PMID- 24353176
TI - Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3
and MyD88 pathways and is associated with alterations in the intestinal
microbiome.
AB - RIP-B7.1 transgenic mice express B7.1 costimulatory molecules in pancreatic
islets and develop diabetes after treatment with polyinosinic:polycytidylic acid
(poly I:C), a synthetic double-stranded RNA and agonist of Toll-like receptor
(TLR) 3 and retinoic acid-inducible protein I. We used this model to investigate
the role of TLR pathways and intestinal microbiota in disease progression. RIP
B7.1 mice homozygous for targeted disruption of TLR9, TLR3, and myeloid
differentiation factor-88 (MyD88), and most of the wild-type RIP-B7.1 mice housed
under normal conditions remained diabetes-free after poly I:C administration.
However, the majority of TLR9-deficient mice and wild-type animals treated with
poly I:C and an antibiotic developed disease. In sharp contrast, TLR3- and MyD88
deficient mice were protected from diabetes following the same treatment regimen.
High-throughput DNA sequencing demonstrated that TLR9-deficient mice treated with
antibiotics plus poly I:C had higher bacterial diversity compared with disease
resistant mice. Furthermore, principal component analysis suggested that TLR9
deficient mice had distinct gut microbiome compared with the diabetes-resistant
mice. Finally, the administration of sulfatrim plus poly I:C to TLR9-deficient
mice resulted in alterations in the abundance of gut bacterial communities at the
phylum and genus levels. These data imply that the induction of diabetes in the
RIP-B7.1 model is critically dependent on TLR3 and MyD88 pathways, and involves
modulation of the intestinal microbiota.
PMID- 24353177
TI - Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin
sensitivity in obese subjects.
AB - Oxidative stress is purported to be involved in the pathogenesis of obesity
associated insulin resistance. We evaluated whether alterations in levels of
circulating uric acid (UA), a systemic antioxidant, affects the following: 1)
systemic (plasma and saliva) nonenzymatic antioxidant capacity (NEAC); 2) markers
of systemic (urinary 8-iso-prostaglandin-F2alpha) and muscle (carbonylated
protein content) oxidative stress; and 3) whole-body insulin sensitivity
(percentage increase in glucose uptake during a hyperinsulinemic-euglycemic clamp
procedure). Thirty-one obese subjects (BMI 37.1 +/- 0.7 kg/m(2)) with either high
serum UA (HUA; 7.1 +/- 0.4 mg/dL; n = 15) or normal serum UA (NUA; 4.5 +/- 0.2
mg/dL; n = 16) levels were studied; 13 subjects with HUA levels were studied
again after reduction of serum UA levels to 0 by infusing a recombinant urate
oxidase. HUA subjects had 20-90% greater NEAC, but lower insulin sensitivity
(40%) and levels of markers of oxidative stress (30%) than subjects in the NUA
group (all P < 0.05). Acute UA reduction caused a 45-95% decrease in NEAC and a
25-40% increase in levels of systemic and muscle markers of oxidative stress (all
P < 0.05), but did not affect insulin sensitivity (from 168 +/- 25% to 156 +/-
17%, P = NS). These results demonstrate that circulating UA is a major
antioxidant and might help protect against free-radical oxidative damage.
However, oxidative stress is not a major determinant of insulin action in vivo.
PMID- 24353178
TI - Elevated mouse hepatic betatrophin expression does not increase human beta-cell
replication in the transplant setting.
AB - The recent discovery of betatrophin, a protein secreted by the liver and white
adipose tissue in conditions of insulin resistance and shown to dramatically
stimulate replication of mouse insulin-producing beta-cells, has raised high
hopes for the rapid development of a novel therapeutic approach for the treatment
of diabetes. At present, however, the effects of betatrophin on human beta-cells
are not known. Here we use administration of the insulin receptor antagonist
S961, shown to increase betatrophin gene expression and stimulate beta-cell
replication in mice, to test its effect on human beta-cells. Although mouse beta
cells, in their normal location in the pancreas or when transplanted under the
kidney capsule, respond with a dramatic increase in beta-cell DNA replication,
human beta-cells are completely unresponsive. These results put into question
whether betatrophin can be developed as a therapeutic approach for treating human
diabetes.
PMID- 24353179
TI - Proinsulin-transferrin fusion protein as a novel long-acting insulin analog for
the inhibition of hepatic glucose production.
AB - Proinsulin-transferrin (ProINS-Tf) fusion protein was evaluated for its in vivo
pharmacokinetics, efficacy, and mechanism. Our previous studies have shown that
ProINS-Tf was converted to active insulin-transferrin (INS-Tf) via the
transferrin (Tf)-receptor-mediated pathway in hepatoma cells. We hypothesized
that this fusion protein can be administered as a prodrug and be converted to a
biologically active protein with specificity for the liver versus other insulin
(INS)-sensitive tissues (muscle and adipose). Administration as an inactive
prodrug with liver-specific action compared with other INS-sensitive tissues
conceivably reduces negative side effects seen with other INS analogs. In this
report, the data show that ProINS-Tf exhibited a slow, but sustained, in vivo
hypoglycemic efficacy and long plasma half-life. The fusion protein showed
activity in the liver, as evidenced by decreased expression of two key hepatic
glucose production (HGP) enzymes, PEPCK and glucose-6-phosphatase, and increased
glycogen levels under feeding conditions. Furthermore, the INS receptor (IR)
phosphorylation (activation) in liver and muscle tissues was compared with
postinjection of INS or ProINS-Tf. While INS activated IR in both the liver and
muscle, ProINS-Tf only showed activation in the liver. Thus, ProINS-Tf fusion
protein can potentially be administered as a prodrug with sustained Tf-mediated
activation and selectivity in inhibiting HGP.
PMID- 24353180
TI - Chronic reduction of plasma free fatty acid improves mitochondrial function and
whole-body insulin sensitivity in obese and type 2 diabetic individuals.
AB - Insulin resistance and dysregulation of free fatty acid (FFA) metabolism are core
defects in type 2 diabetic (T2DM) and obese normal glucose tolerant (NGT)
individuals. Impaired muscle mitochondrial function (reduced ATP synthesis) also
has been described in insulin-resistant T2DM and obese subjects. We examined
whether reduction in plasma FFA concentration with acipimox improved ATP
synthesis rate and altered reactive oxygen species (ROS) production. Eleven NGT
obese and 11 T2DM subjects received 1) OGTT, 2) euglycemic insulin clamp with
muscle biopsy, and 3) (1)H-magnetic resonance spectroscopy of tibialis anterior
muscle before and after acipimox (250 mg every 6 h for 12 days). ATP synthesis
rate and ROS generation were measured in mitochondria isolated from muscle tissue
ex vivo with chemoluminescence and fluorescence techniques, respectively.
Acipimox 1) markedly reduced the fasting plasma FFA concentration and enhanced
suppression of plasma FFA during oral glucose tolerance tests and insulin clamp
in obese NGT and T2DM subjects and 2) enhanced insulin-mediated muscle glucose
disposal and suppression of hepatic glucose production. The improvement in
insulin sensitivity was closely correlated with the decrease in plasma FFA in
obese NGT (r = 0.81) and T2DM (r = 0.76) subjects (both P < 0.001). Mitochondrial
ATP synthesis rate increased by >50% in both obese NGT and T2DM subjects and was
strongly correlated with the decrease in plasma FFA and increase in insulin
mediated glucose disposal (both r > 0.70, P < 0.001). Production of ROS did not
change after acipimox. Reduction in plasma FFA in obese NGT and T2DM individuals
improves mitochondrial ATP synthesis rate, indicating that the mitochondrial
defect in insulin-resistant individuals is, at least in part, reversible.
PMID- 24353181
TI - Body fat partitioning does not explain the interethnic variation in insulin
sensitivity among Asian ethnicity: the Singapore adults metabolism study.
AB - We previously showed that ethnicity modifies the association between adiposity
and insulin resistance. We sought to determine whether differential body fat
partitioning or abnormalities in muscle insulin signaling associated with higher
levels of adiposity might underlie this observation. We measured the insulin
sensitivity index (ISI), percentage of body fat (%body fat), visceral (VAT) and
subcutaneous (SAT) adipose tissue, liver fat, and intramyocellular lipids (IMCL)
in 101 Chinese, 82 Malays, and 81 South Asians, as well as phosphorylated (p)-Akt
levels in cultured myoblasts from Chinese and South Asians. Lean Chinese and
Malays had higher ISI than South Asians. Although the ISI was lower in all ethnic
groups when %body fat was higher, this association was stronger in Chinese and
Malays, such that no ethnic differences were observed in overweight individuals.
These ethnic differences were observed even when %body fat was replaced with fat
in other depots. Myoblasts obtained from lean South Asians had lower p-Akt levels
than those from lean Chinese. Higher adiposity was associated with lower p-Akt
levels in Chinese but not in South Asians, and no ethnic differences were
observed in overweight individuals. With higher %body fat, Chinese exhibited
smaller increases in deep SAT and IMCL compared with Malays and South Asians,
which did not explain the ethnic differences observed. Our study suggests that
body fat partitioning does not explain interethnic differences in insulin
sensitivity among Asian ethnic groups. Although higher adiposity had greater
effect on skeletal muscle insulin sensitivity among Chinese, obesity-independent
pathways may be more relevant in South Asians.
PMID- 24353182
TI - Peroxynitrite disrupts endothelial caveolae leading to eNOS uncoupling and
diminished flow-mediated dilation in coronary arterioles of diabetic patients.
AB - Peroxynitrite (ONOO(-)) contributes to coronary microvascular dysfunction in
diabetes mellitus (DM). We hypothesized that in DM, ONOO(-) interferes with the
function of coronary endothelial caveolae, which plays an important role in
nitric oxide (NO)-dependent vasomotor regulation. Flow-mediated dilation (FMD) of
coronary arterioles was investigated in DM (n = 41) and non-DM (n = 37) patients
undergoing heart surgery. NO-mediated coronary FMD was significantly reduced in
DM patients, which was restored by ONOO(-) scavenger, iron-(III)-tetrakis(N
methyl-4'pyridyl)porphyrin-pentachloride, or uric acid, whereas exogenous ONOO(-)
reduced FMD in non-DM subjects. Immunoelectron microscopy demonstrated an
increased 3-nitrotyrosine formation (ONOO(-)-specific protein nitration) in
endothelial plasma membrane in DM, which colocalized with caveolin-1 (Cav-1), the
key structural protein of caveolae. The membrane-localized Cav-1 was
significantly reduced in DM and also in high glucose-exposed coronary endothelial
cells. We also found that DM patients exhibited a decreased number of endothelial
caveolae, whereas exogenous ONOO(-) reduced caveolae number. Correspondingly,
pharmacological (methyl-beta-cyclodextrin) or genetic disruption of caveolae (Cav
1 knockout mice) abolished coronary FMD, which was rescued by sepiapterin, the
stable precursor of NO synthase (NOS) cofactor, tetrahydrobiopterin. Sepiapterin
also restored coronary FMD in DM patients. Thus, we propose that ONOO(-)
selectively targets and disrupts endothelial caveolae, which contributes to NOS
uncoupling, and, hence, reduced NO-mediated coronary vasodilation in DM patients.
PMID- 24353183
TI - Rap1 ameliorates renal tubular injury in diabetic nephropathy.
AB - Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular
cells. However, its role and precise mechanism in diabetic nephropathy (DN) in
vivo remain unclear. We hypothesize that Rap1 plays a protective role in tubular
damage of DN by modulating primarily the mitochondria-derived oxidative stress.
The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of
tubular cells in DN were examined in rats with streptozotocin (STZ)-induced
diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated
technique as well as in renal proximal epithelial tubular cell line (HK-2)
exposed to HG ambiance. The results showed that Rap1b expression decreased
significantly in tubules of renal biopsies from patients with DN. Overexpression
of a constitutively active Rap1b G12V notably ameliorated renal tubular
mitochondrial dysfunction, oxidative stress, and apoptosis in the kidneys of STZ
induced rats, which was accompanied with increased expression of transcription
factor C/EBP-beta and PGC-1alpha. Furthermore, Rap1b G12V also decreased
phosphorylation of Drp-1, a key mitochondrial fission protein, while boosting the
expression of genes related to mitochondrial biogenesis and antioxidants in HK-2
cells induced by HG. These effects were imitated by transfection with C/EBP-beta
or PGC-1alpha short interfering RNA. In addition, Rap1b could modulate C/EBP-beta
binding to the endogenous PGC-1alpha promoter and the interaction between PGC
1alpha and catalase or mitochondrial superoxide dismutase, indicating that Rap1b
ameliorates tubular injury and slows the progression of DN by modulation of
mitochondrial dysfunction via C/EBP-beta-PGC-1alpha signaling.
PMID- 24353184
TI - Failure of homeostatic model assessment of insulin resistance to detect marked
diet-induced insulin resistance in dogs.
AB - Accurate quantification of insulin resistance is essential for determining
efficacy of treatments to reduce diabetes risk. Gold-standard methods to assess
resistance are available (e.g., hyperinsulinemic clamp or minimal model), but
surrogate indices based solely on fasting values have attractive simplicity. One
such surrogate, the homeostatic model assessment of insulin resistance (HOMA-IR),
is widely applied despite known inaccuracies in characterizing resistance across
groups. Of greater significance is whether HOMA-IR can detect changes in insulin
sensitivity induced by an intervention. We tested the ability of HOMA-IR to
detect high-fat diet-induced insulin resistance in 36 healthy canines using clamp
and minimal model analysis of the intravenous glucose tolerance test (IVGTT) to
document progression of resistance. The influence of pancreatic function on HOMA
IR accuracy was assessed using the acute insulin response during the IVGTT
(AIRG). Diet-induced resistance was confirmed by both clamp and minimal model (P
< 0.0001), and measures were correlated with each other (P = 0.001). In striking
contrast, HOMA-IR ([fasting insulin (MUU/mL) * fasting glucose (mmol)]/22.5) did
not detect reduced sensitivity induced by fat feeding (P = 0.22). In fact, 13 of
36 animals showed an artifactual decrease in HOMA-IR (i.e., increased
sensitivity). The ability of HOMA-IR to detect diet-induced resistance was
particularly limited under conditions when insulin secretory function (AIRG) is
less than robust. In conclusion, HOMA-IR is of limited utility for detecting diet
induced deterioration of insulin sensitivity quantified by glucose clamp or
minimal model. Caution should be exercised when using HOMA-IR to detect insulin
resistance when pancreatic function is compromised. It is necessary to use other
accurate indices to detect longitudinal changes in insulin resistance with any
confidence.
PMID- 24353185
TI - Altered spontaneous brain activity in type 2 diabetes: a resting-state functional
MRI study.
AB - Previous research has shown that type 2 diabetes mellitus (T2DM) is associated
with an increased risk of cognitive impairment. Patients with impaired cognition
often show decreased spontaneous brain activity on resting-state functional
magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate
changes in spontaneous brain activity among patients with T2DM and to determine
the relationship of these changes with cognitive impairment. T2DM patients (n =
29) and age-, sex-, and education-matched healthy control subjects (n = 27) were
included in this study. Amplitude of low-frequency fluctuation (ALFF) and
regional homogeneity (ReHo) values were calculated to represent spontaneous brain
activity. Brain volume and cognition were also evaluated among these
participants. Compared with healthy control subjects, patients with T2DM had
significantly decreased ALFF and ReHo values in the occipital lobe and
postcentral gyrus. Patients performed worse on several cognitive tests; this
impaired cognitive performance was correlated with decreased activity in the
cuneus and lingual gyrus in the occipital lobe. Brain volume did not differ
between the two groups. The abnormalities of spontaneous brain activity reflected
by ALFF and ReHo measurements in the absence of structural changes in T2DM
patients may provide insights into the neurological pathophysiology underlying
diabetes-associated cognitive decline.
PMID- 24353186
TI - Deficiency in type I interferon signaling prevents the early interferon-induced
gene signature in pancreatic islets but not type 1 diabetes in NOD mice.
AB - Type I interferons (IFNs) have been implicated in the initiation of islet
autoimmunity and development of type 1 diabetes. To directly test their
involvement, we generated NOD mice deficient in type I IFN receptors (NOD.IFNAR1(
/-)). Expression of the type I IFN-induced genes Mx1, Isg15, Ifit1, Oas1a, and
Cxcr4 was detectable in NOD islets as early as 1 week of age. Of these five
genes, expression of Isg15, Ifit1, Oas1a, and Mx1 peaked at 3-4 weeks of age,
corresponding with an increase in Ifnalpha mRNA, declined at 5-6 weeks of age,
and increased again at 10-14 weeks of age. Increased IFN-induced gene expression
was ablated in NOD.IFNAR1(-/-) islets. Loss of Toll-like receptor 2 (TLR2)
resulted in reduced islet expression of Mx1 at 2 weeks of age, but TLR2 or TLR9
deficiency did not change the expression of other IFN-induced genes in islets
compared with wild-type NOD islets. We observed increased beta-cell major
histocompatibility complex class I expression with age in NOD and NOD.IFNAR1(-/-)
mice. NOD.IFNAR1(-/-) mice developed insulitis and diabetes at a similar rate to
NOD controls. These results indicate type I IFN is produced within islets in
young mice but is not essential for the initiation and progression of diabetes in
NOD mice.
PMID- 24353187
TI - Zonisamide add-on for drug-resistant partial epilepsy.
AB - BACKGROUND: The majority of people with epilepsy have a good prognosis and their
seizures can be well controlled with the use of a single antiepileptic agent, but
up to 30% develop refractory epilepsy, especially those with partial seizures. In
this review we summarise the current evidence regarding zonisamide, when used as
an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate
the efficacy and tolerability of zonisamide when used as an add-on treatment for
people with drug-resistant partial epilepsy. SEARCH METHODS: We searched the
Cochrane Epilepsy Group Specialized Register (12 February 2013), the Cochrane
Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1)
(January 2013), MEDLINE (Ovid, 1946 to 12 February 2013), SCOPUS (13 February
2013), ClinicalTrials.gov (12 February 2013) and the WHO International Clinical
Trials Registry Platform ICTRP (13 February 2013). In addition, we contacted
Eisai Limited (makers and licensees of zonisamide) and experts in the field to
seek any ongoing/unpublished studies. SELECTION CRITERIA: Randomised, placebo
controlled, add-on trials of zonisamide in people with drug-resistant partial
epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
trials for inclusion and extracted data. Outcomes were: (1) 50% or greater
reduction in total seizure frequency; (2) treatment withdrawal; (3) adverse
effects. Primary analyses were intention-to-treat. We estimated summary risk
ratios (RRs) for each outcome. All studies were assessed for risk of bias using
the Cochrane risk of bias tool and the quality of evidence was assessed using the
GRADE approach and presented in a summary of findings table. MAIN RESULTS: Five
trials (949 participants) were included. The overall RR with 95% confidence
interval (CI) for 50% reduction in seizure frequency compared to placebo for 300
to 500 mg/day of zonisamide was 2.00 (95% CI 1.58 to 2.54). The RR for 50%
reduction in seizure frequency compared to placebo for any dose of zonisamide
(100 to 500 mg per day) was 1.92 (95% CI 1.52 to 2.42). The number needed to
treat (NNT) was 6 for this outcome. Two trials provide evidence of a dose
response relationship for this outcome. The RR for treatment withdrawal for 300
to 500 mg/day of zonisamide compared to placebo was 1.64 (95% CI 1.20 to 2.25)
and for 100 to 500 mg per day was 1.47 (95% CI 1.07 to 2.01). NNT for this
outcome was 21. The CIs of the following adverse effects indicate that they are
significantly associated with zonisamide: ataxia 3.77 (99% CI 1.28 to 11.11);
somnolence 1.83 (99% CI 1.08 to 3.11); agitation 2.35 (99% CI 1.05 to 5.27) and
anorexia 2.71 (99% CI 1.29 to 5.69). Across the 5 studies, risk of bias domains
were rated as low is bias or unclear. None of the evidence for outcomes was
downgraded for quality. AUTHORS' CONCLUSIONS: Zonisamide has efficacy as an add
on treatment in people with drug-resistant partial epilepsy. In this review
minimum effective and maximum tolerated doses cannot be identified. The trials
reviewed were of a maximum stable-dose phase of 18 weeks in duration and results
cannot be used to confirm longer periods of effectiveness in seizure control. The
results cannot be extrapolated to monotherapy or to people with other seizure
types or epilepsy syndromes.
PMID- 24353188
TI - Mountain landscapes offer few opportunities for high-elevation tree species
migration.
AB - Climate change is anticipated to alter plant species distributions. Regional
context, notably the spatial complexity of climatic gradients, may influence
species migration potential. While high-elevation species may benefit from steep
climate gradients in mountain regions, their persistence may be threatened by
limited suitable habitat as land area decreases with elevation. To untangle these
apparently contradictory predictions for mountainous regions, we evaluated the
climatic suitability of four coniferous forest tree species of the western United
States based on species distribution modeling (SDM) and examined changes in
climatically suitable areas under predicted climate change. We used forest
structural information relating to tree species dominance, productivity, and
demography from an extensive forest inventory system to assess the strength of
inferences made with a SDM approach. We found that tree species dominance,
productivity, and recruitment were highest where climatic suitability (i.e.,
probability of species occurrence under certain climate conditions) was high,
supporting the use of predicted climatic suitability in examining species risk to
climate change. By predicting changes in climatic suitability over the next
century, we found that climatic suitability will likely decline, both in areas
currently occupied by each tree species and in nearby unoccupied areas to which
species might migrate in the future. These trends were most dramatic for high
elevation species. Climatic changes predicted over the next century will
dramatically reduce climatically suitable areas for high-elevation tree species
while a lower elevation species, Pinus ponderosa, will be well positioned to
shift upslope across the region. Reductions in suitable area for high-elevation
species imply that even unlimited migration would be insufficient to offset
predicted habitat loss, underscoring the vulnerability of these high-elevation
species to climatic changes.
PMID- 24353189
TI - Fast, sensitive, and reliable.
PMID- 24353190
TI - Differences in sialic acid O-acetylation between human urinary and recombinant
erythropoietins: a possible mass spectrometric marker for doping control.
AB - Development of a mass spectrometric method for the unambiguous detection of
doping with recombinant human erythropoietins (rhEPO) has been attempted for many
years. Unfortunately, progress in this field was hampered by the unavailability
of highly purified human endogenous EPOs (urinary[uhEPO], serum/plasma EPO)--a
prerequisite for generating detailed mass spectrometric glycosylation data
necessary for revealing significant differences between uhEPO and rhEPOs. The
paper presents the worldwide first analytical data on purified human urinary EPO
generated with a high resolution high accuracy mass spectrometer (LTQ-Orbitrap).
The focus is on the tryptic O-glycopeptide (E117-R131) and its degree of sialic
acid O-acetylation. Data are compared with results obtained from 40 rhEPO
pharmaceuticals. It could be demonstrated that the O-glycopeptide of uhEPO (ca
100 IU) contains only trace amounts of mono-acetylated mono-and di-sialylated O
glycans but no other O-acetylated structures and in this respect significantly
differs from all rhEPOs. Moreover, Dynepo--a rhEPO previously thought to be not O
acetylated--also contains small amounts of O-acetylations within the O-glycan
structure. The results might be useful for anti-doping purposes as well as the
development of EPO pharmaceuticals with closer structural similarity to the
endogenous hormone.
PMID- 24353191
TI - A population study of urine glycerol concentrations in elite athletes competing
in North America.
AB - Glycerol is an endogenous substance that is on the World Anti-Doping Agency's
list of prohibited threshold substances due to its potential use as a plasma
volume expansion agent. The WADA has set the threshold for urine glycerol,
including measurement uncertainty, at 1.3 mg/mL. Glycerol in circulation largely
comes from metabolism of triglycerides in order to meet energy requirements and
when the renal threshold is eclipsed, glycerol is excreted into urine. In part
due to ethnic differences in postprandial triglyceride concentrations, we
investigated urine glycerol concentrations in a population of elite athletes
competing in North America and compared the results to those of athletes
competing in Europe. 959 urine samples from elite athletes competing in North
America collected for anti-doping purposes were analyzed for urine glycerol
concentrations by a gas chromatography mass-spectrometry method. Samples were
divided into groups according to: Timing (in- or out-of-competition), Class
(strength, game, or endurance sports) and Gender. 333 (34.7%) samples had
undetectable amounts of glycerol (<1 MUg/mL). 861 (89.8%) of the samples had
glycerol concentrations <=20 MUg/mL. The highest glycerol concentration observed
was 652 MUg/mL. Analysis of the data finds the effects of each category to be
statistically significant. The largest estimate of the 99.9(th) percentile, from
the in-competition, female, strength athlete samples, was 1813 MUg/mL with a 95%
confidence range from 774 to 4251 MUg/mL. This suggests a conservative threshold
of 4.3 mg/mL, which would result in a reasonable detection window for urine
samples collected in-competition for all genders and sport classes.
PMID- 24353192
TI - Meta-analysis: Effects of glycerol administration on plasma volume, haemoglobin,
and haematocrit.
AB - The use of glycerol in combination with excess fluid can be used to increase
total body water. Because glycerol hyperhydration may also be misused to mask the
effects of blood doping on doping-relevant parameters, namely haemoglobin and
haematocrit, glycerol has been prohibited by the World Anti-Doping Agency since
2010. In order to test this rationale, the purpose of this meta-analysis was to
quantify the effects of glycerol hyperhydration on plasma volume, haemoglobin,
and haematocrit in comparison to administration of fluid only. Following a
literature search, a total of seven studies was included and meta-analyses were
performed separately for the effects on plasma volume (5 studies, total n = 54)
and on haemoglobin (6 studies, n = 52) and haematocrit (6 studies, n = 52). The
meta-analysis revealed that the increase in plasma volume was 3.3% larger (95%
CI: 1.1-5.5%) after glycerol administration when compared to fluid only.
Reductions in haemoglobin were 0.2 g/dl (95%-CI: -0.3, 0.0) larger and there was
no difference in the changes in haematocrit between glycerol and fluid
administration (95%-CI: -0.7-0.8%). In comparison with other plasma-volume
expanding agents, glycerol hyperhydration has a very limited potential in
increasing plasma volume and altering doping-relevant blood parameters.
PMID- 24353194
TI - Gradient structure-induced temperature responsiveness in styrene/methyl
methacrylate gradient copolymers micelles.
AB - In this work, micelles are formed by gradient copolymer of styrene and methyl
methacrylate in acetone-water mixture and their temperature responsiveness is
investigated in a narrow range near room temperature. Three different kinds of
structural transitions could be induced by temperature: unimers to micelle
transition, shrinkage/stretching of micelles, and morphological transition from
spherical micelles to vesicles. In addition, a model analysis on the interface of
gradient copolymer micelle is made to better understand these phenomena. It is
found that both position and composition of the interface could alter in response
to the change in temperature. According to the experiments and model analysis, it
is proposed that temperature responsiveness might be an intrinsic and universal
property of gradient copolymer micelles, which only originates from the gradient
structure.
PMID- 24353195
TI - Dietary protein restriction inhibits tumor growth in human xenograft models.
AB - PURPOSE: Data from epidemiological and experimental studies suggest that dietary
protein intake may play a role in inhibiting prostate and breast cancer by
modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of
diets with different protein content or quality on prostate and breast cancer.
EXPERIMENTAL DESIGN: To test our hypothesis we assessed the inhibitory effect of
protein diet restriction on prostate and breast cancer growth, serum PSA and IGF
1 concentrations, mTOR activity and epigenetic markers, by using human xenograft
cancer models. RESULTS: Our results showed a 70% inhibition of tumor growth in
the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in
the WHIM16 breast cancer model fed with a 7% protein diet when compared to an
isocaloric 21% protein diet. Inhibition of tumor growth correlated, in the
LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of
mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and
reduction in epigenetic markers of prostate cancer progression, including the
histone methyltransferase EZH2 and the associated histone mark H3K27me3. In
addition, we observed that modifications of dietary protein quality,
independently of protein quantity, decreased tumor growth. A diet containing 20%
plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy
protein diet. CONCLUSIONS: Our findings suggest that a reduction in dietary
protein intake is highly effective in inhibiting tumor growth in human xenograft
prostate and breast cancer models, possibly through the inhibition of the
IGF/AKT/mTOR pathway and epigenetic modifications.
PMID- 24353197
TI - Scanning droplet cell for chemoselective patterning through local
electroactivation of protected quinone monolayers.
AB - A reagentless strategy for template-free patterning of uniformly inert surfaces
is suggested. A layer of p-hydroquinone (HQ) protected by the tert
butyldimethylsilyl (TBDMS) group is electrografted onto glassy carbon electrodes.
Chemoselective activation is performed through electrochemically controlled
cleavage of the TBDMS group, which yields the redox-active surface-confined
quinone moieties. The latter are shown to undergo electrochemically induced
Michael addition, which serves for subsequent functionalization of the electrode
surface. Patterning of the TBDMS-quinone-modified surface is accomplished by
using selective localized cleavage of the protecting group. State-of-the-art
direct-mode scanning electrochemical microscopy (SECM) patterning fails to yield
the anticipated interfacial reaction; however, the electrochemical scanning
droplet cell (SDC) is capable of conducting the localized chemoselective
reaction. In a small area, dictated by the dimensions of the droplet,
electrochemically induced cleavage of the protecting group can be performed
locally to give rise to arrays of active quinone spots. Upon deprotection, the
redox signals, attributed to the hydroquinone/benzoquinone couple, provide the
first direct evidence for chemoselective electrochemical patterning of sensitive
functionalities. Subsequent SECM studies of the resulting modified areas
demonstrate spatial control of the proposed patterning technique.
PMID- 24353196
TI - Triggers of fear: perceptual cues versus conceptual information in spider phobia.
AB - OBJECTIVE: Fear reactions in spider-phobic patients can be activated by specific
perceptual cues or by conceptual fear-related information. Matching perceptual
fear cues and fear-related information were expected to result in maximal fear
responses, perceptual fear cues alone in less fear, and information alone in the
weakest responses. METHOD: We used virtual reality to manipulate the available
cues and information. Forty-eight phobic patients and 48 healthy participants
were repeatedly exposed to either a perceptual cue, information, or a combination
of both. RESULTS: In conditions with a fear-relevant perceptual cue, phobic
patients reported increased fear compared to the condition with information only.
Across exposures trials, these reactions diminished. Skin conductance in phobic
patients was significantly higher in the combined than in the cue or the
information condition. CONCLUSIONS: Perceptual cues are essential for phobic fear
reactions in spider phobia. In combination with fear-relevant information,
perceptual cues activate an intense and persistent fear reaction.
PMID- 24353198
TI - Stress.
PMID- 24353199
TI - Molecular basis of chill resistance adaptations in poikilothermic animals.
AB - Chill and freeze represent very different components of low temperature stress.
Whilst the principal mechanisms of tissue damage and of acquired protection from
freeze-induced effects are reasonably well established, those for chill damage
and protection are not. Non-freeze cold exposure (i.e. chill) can lead to serious
disruption to normal life processes, including disruption to energy metabolism,
loss of membrane perm-selectivity and collapse of ion gradients, as well as loss
of neuromuscular coordination. If the primary lesions are not relieved then the
progressive functional debilitation can lead to death. Thus, identifying the
underpinning molecular lesions can point to the means of building resistance to
subsequent chill exposures. Researchers have focused on four specific lesions:
(i) failure of neuromuscular coordination, (ii) perturbation of bio-membrane
structure and adaptations due to altered lipid composition, (iii) protein
unfolding, which might be mitigated by the induced expression of compatible
osmolytes acting as 'chemical chaperones', (iv) or the induced expression of
protein chaperones along with the suppression of general protein synthesis.
Progress in all these potential mechanisms has been ongoing but not substantial,
due in part to an over-reliance on straightforward correlative approaches. Also,
few studies have intervened by adoption of single gene ablation, which provides
much more direct and compelling evidence for the role of specific genes, and thus
processes, in adaptive phenotypes. Another difficulty is the existence of
multiple mechanisms, which often act together, thus resulting in compensatory
responses to gene manipulations, which may potentially mask disruptive effects on
the chill tolerance phenotype. Consequently, there is little direct evidence of
the underpinning regulatory mechanisms leading to induced resistance to chill
injury. Here, we review recent advances mainly in lower vertebrates and in
arthropods, but increasingly in genetic model species from a broader range of
taxa.
PMID- 24353200
TI - Acclimation and thermal tolerance in Antarctic marine ectotherms.
AB - Antarctic marine species have evolved in one of the coldest and most temperature
stable marine environments on Earth. They have long been classified as being
stenothermal, or having a poor capacity to resist warming. Here we show that
their ability to acclimate their physiology to elevated temperatures is poor
compared with species from temperate latitudes, and similar to those from the
tropics. Those species that have been demonstrated to acclimate take a very long
time to do so, with Antarctic fish requiring up to 21-36 days to acclimate, which
is 2-4 times as long as temperate species, and invertebrates requiring between 2
and 5 months to complete whole-animal acclimation. Investigations of upper
thermal tolerance (CT(max)) in Antarctic marine species have shown that as the
rate of warming is reduced in experiments, CT(max) declines markedly, ranging
from 8 to 17.5 degrees C across 13 species at a rate of warming of 1 degrees C
day(-1), and from 1 to 6 degrees C at a rate of 1 degrees C month(-1). This
effect of the rate of warming on CT(max) also appears to be present at all
latitudes. A macrophysiological analysis of long-term CT(max) across latitudes
for marine benthic groups showed that both Antarctic and tropical species were
less resistant to elevated temperatures in experiments and thus had lower warming
allowances (measured as the difference between long-term CT(max) and experienced
environmental temperature), or warming resistance, than temperate species. This
makes them more at risk from warming than species from intermediate latitudes.
This suggests that the variability of environmental temperature may be a major
factor in dictating an organism's responses to environmental change.
PMID- 24353202
TI - Mosaic physiology from developmental noise: within-organism physiological
diversity as an alternative to phenotypic plasticity and phenotypic flexibility.
AB - A key problem in organismal biology is to explain the origins of functional
diversity. In the context of organismal biology, functional diversity describes
the set of phenotypes, across scales of biological organization and through time,
that a single genotype, or genome, or organism, can produce. Functional diversity
encompasses many phenomena: differences in cell types within organisms;
physiological and morphological differences among tissues and organs; differences
in performance; morphological shifts in external phenotype; and changes in
behavior. How can single genomes produce so many different phenotypes? Modern
biology proposes two general mechanisms. The first is developmental programs, by
which single cells and their single genomes diversify, via relatively
deterministic processes, into the sets of cell types, tissues and organs that we
see in most multicellular organisms. The second general mechanism is phenotypic
modification stemming from interactions between organisms and their environments
modifications known either as phenotypic plasticity or as phenotypic
flexibility, depending on the time scale of the response and the degree of
reversibility. These two diversity-generating mechanisms are related because
phenotypic modifications may sometimes arise as a consequence of environments
influencing developmental programs. Here, I propose that functional diversity
also arises via a third fundamental mechanism: stochastic developmental events
giving rise to mosaics of physiological diversity within individual organisms. In
biological systems, stochasticity stems from the inherently random actions of
small numbers of molecules interacting with one another. Although stochastic
effects occur in many biological contexts, available evidence suggests that they
can be especially important in gene networks, specifically as a consequence of
low transcript numbers in individual cells. I briefly review known mechanisms by
which organisms control such stochasticity, and how they may use it to create
adaptive functional diversity. I then fold this idea into modern thinking on
phenotypic plasticity and flexibility, proposing that multicellular organisms
exhibit 'mosaic physiology'. Mosaic physiology refers to sets of diversified
phenotypes, within individual organisms, that carry out related functions at the
same time, but that are distributed in space. Mosaic physiology arises from
stochasticity-driven differentiation of cells, early during cell diversification,
which is then amplified by cell division and growth into macroscopic phenotypic
modules (cells, tissues, organs) making up the physiological systems of later
life stages. Mosaic physiology provides a set of standing, diversified
phenotypes, within single organisms, that raise the likelihood of the organism
coping well with novel environmental challenges. These diversified phenotypes can
be distinct, akin to polyphenisms at the organismal level; or they can be
continuously distributed, creating a kind of standing, simultaneously expressed
reaction norm of physiological capacities.
PMID- 24353203
TI - What can an ecophysiological approach tell us about the physiological responses
of marine invertebrates to hypoxia?
AB - Hypoxia (low O2) is a common and natural feature of many marine environments.
However, human-induced hypoxia has been on the rise over the past half century
and is now recognised as a major problem in the world's seas and oceans. Whilst
we have information on how marine invertebrates respond physiologically to
hypoxia in the laboratory, we still lack understanding of how they respond to
such stress in the wild (now and in the future). Consequently, here the question
'what can an ecophysiological approach tell us about physiological responses of
marine invertebrates to hypoxia' is addressed. How marine invertebrates work in
the wild when challenged with hypoxia is explored using four case studies centred
on different hypoxic environments. The recent integration of the various -omics
into ecophysiology is discussed, and a number of advantages of, and challenges
to, successful integration are suggested. The case studies and -omic/physiology
integration data are used to inform the concluding part of the review, where it
is suggested that physiological responses to hypoxia in the wild are not always
the same as those predicted from laboratory experiments. This is due to behaviour
in the wild modifying responses, and therefore more than one type of
'experimental' approach is essential to reliably determine the actual response.
It is also suggested that assuming it is known what a measured response is 'for'
can be misleading and that taking parodies of ecophysiology seriously may impede
research progress. This review finishes with the suggestion that an -omics
approach is, and is becoming, a powerful method of understanding the response of
marine invertebrates to environmental hypoxia and may be an ideal way of studying
hypoxic responses in the wild. Despite centring on physiological responses to
hypoxia, the review hopefully serves as a contribution to the discussion of what
(animal) ecophysiology looks like (or should look like) in the 21st century.
PMID- 24353201
TI - What is environmental stress? Insights from fish living in a variable
environment.
AB - Although the term environmental stress is used across multiple fields in biology,
the inherent ambiguity associated with its definition has caused confusion when
attempting to understand organismal responses to environmental change. Here I
provide a brief summary of existing definitions of the term stress, and the
related concepts of homeostasis and allostasis, and attempt to unify them to
develop a general framework for understanding how organisms respond to
environmental stressors. I suggest that viewing stressors as environmental
changes that cause reductions in performance or fitness provides the broadest and
most useful conception of the phenomenon of stress. I examine this framework in
the context of animals that have evolved in highly variable environments, using
the Atlantic killifish, Fundulus heteroclitus, as a case study. Consistent with
the extreme environmental variation that they experience in their salt marsh
habitats, killifish have substantial capacity for both short-term resistance and
long-term plasticity in the face of changing temperature, salinity and
oxygenation. There is inter-population variation in the sensitivity of killifish
to environmental stressors, and in their ability to acclimate, suggesting that
local adaptation can shape the stress response even in organisms that are broadly
tolerant and highly plastic. Whole-organism differences between populations in
stressor sensitivity and phenotypic plasticity are reflected at the biochemical
and molecular levels in killifish, emphasizing the integrative nature of the
response to environmental stressors. Examination of this empirical example
highlights the utility of using an evolutionary perspective on stressors, stress
and stress responses.
PMID- 24353204
TI - Organismal stress, telomeres and life histories.
AB - Most organisms, including ourselves, are exposed to environmental stressors at
various points during life, and responses to such stressors have been optimised
by evolution to give the best fitness outcomes. It is expected that environmental
change will substantially increase long-term stress exposure in many animal
groups in the coming decades. A major challenge for biologists is to understand
and predict how this will influence individuals, populations and ecosystems, and
over what time scale such effects will occur. This requires a multi-disciplinary
approach, combining studies of mechanisms with studies of fitness consequences
for individuals and their descendants. In this review, I discuss the positive and
negative fitness consequences of responses to stressful environments,
particularly during early life, and with an emphasis on studies in birds. As many
of the mechanisms underlying stress responses are highly conserved across the
vertebrate groups, the findings from these studies have general applicability
when interpreted in a life history context. One important route that has recently
been identified whereby chronic stress exposure can affect health and longevity
over long time frames is via effects on telomere dynamics. Much of this work has
so far been done on humans, and is correlational in nature, but studies on other
taxa, and experimental work, are increasing. I summarise the relevant aspects of
vertebrate telomere biology and critically appraise our current knowledge with a
view to pointing out important future research directions for our understanding
of how stress exposure influences life histories.
PMID- 24353205
TI - The role of gibberellin signalling in plant responses to abiotic stress.
AB - Plant hormones are small molecules that regulate plant growth and development, as
well as responses to changing environmental conditions. By modifying the
production, distribution or signal transduction of these hormones, plants are
able to regulate and coordinate both growth and/or stress tolerance to promote
survival or escape from environmental stress. A central role for the gibberellin
(GA) class of growth hormones in the response to abiotic stress is becoming
increasingly evident. Reduction of GA levels and signalling has been shown to
contribute to plant growth restriction on exposure to several stresses, including
cold, salt and osmotic stress. Conversely, increased GA biosynthesis and
signalling promote growth in plant escape responses to shading and submergence.
In several cases, GA signalling has also been linked to stress tolerance. The
transcriptional regulation of GA metabolism appears to be a major point of
regulation of the GA pathway, while emerging evidence for interaction of the GA
signalling molecule DELLA with components of the signalling pathway for the
stress hormone jasmonic acid suggests additional mechanisms by which GA
signalling may integrate multiple hormone signalling pathways in the response to
stress. Here, we review the evidence for the role of GA in these processes, and
the regulation of the GA signalling pathway on exposure to abiotic stress. The
potential mechanisms by which GA signalling modulates stress tolerance are also
discussed.
PMID- 24353206
TI - Environmentally relevant stressors alter memory formation in the pond snail
Lymnaea.
AB - Stress alters adaptive behaviours such as learning and memory. Stressors can
either enhance or diminish learning, memory formation and/or memory recall. We
focus attention here on how environmentally relevant stressors alter learning,
memory and forgetting in the pond snail, Lymnaea stagnalis. Operant conditioning
of aerial respiration causes associative learning that may lead to long-term
memory (LTM) formation. However, individual ecologically relevant stressors,
combinations of stressors, and bio-active substances can alter whether or not
learning occurs or memory forms. While the behavioural memory phenotype may be
similar as a result of exposure to different stressors, how each stressor alters
memory formation may occur differently. In addition, when a combination of
stressors are presented it is difficult to predict ahead of time what the outcome
will be regarding memory formation. Thus, how combinations of stressors act is an
emergent property of how the snail perceives the stressors.
PMID- 24353207
TI - Surviving in a frozen desert: environmental stress physiology of terrestrial
Antarctic arthropods.
AB - Abiotic stress is one of the primary constraints limiting the range and success
of arthropods, and nowhere is this more apparent than Antarctica. Antarctic
arthropods have evolved a suite of adaptations to cope with extremes in
temperature and water availability. Here, we review the current state of
knowledge regarding the environmental physiology of terrestrial arthropods in
Antarctica. To survive low temperatures, mites and Collembola are freeze
intolerant and rely on deep supercooling, in some cases supercooling below -30
degrees C. Also, some of these microarthropods are capable of cryoprotective
dehydration to extend their supercooling capacity and reduce the risk of
freezing. In contrast, the two best-studied Antarctic insects, the midges Belgica
antarctica and Eretmoptera murphyi, are freeze-tolerant year-round and rely on
both seasonal and rapid cold-hardening to cope with decreases in temperature. A
common theme among Antarctic arthropods is extreme tolerance of dehydration; some
accomplish this by cuticular mechanisms to minimize water loss across their
cuticle, while a majority have highly permeable cuticles but tolerate upwards of
50-70% loss of body water. Molecular studies of Antarctic arthropod stress
physiology are still in their infancy, but several recent studies are beginning
to shed light on the underlying mechanisms that govern extreme stress tolerance.
Some common themes that are emerging include the importance of cuticular and
cytoskeletal rearrangements, heat shock proteins, metabolic restructuring and
cell recycling pathways as key mediators of cold and water stress in the
Antarctic.
PMID- 24353208
TI - Neurobiological disease etiology and inheritance: an epigenetic perspective.
AB - Epigenetic marks in mammals are essential to properly control the activity of the
genome. They are dynamically regulated during development and adulthood, and can
be modulated by environmental factors throughout life. Changes in the epigenetic
profile of a cell can be positive and favor the expression of advantageous genes
such as those linked to cell signaling and tumor suppression. However, they can
also be detrimental and alter the functions of important genes, thereby leading
to disease. Recent evidence has further highlighted that some epigenetic marks
can be maintained across meiosis and be transmitted to the subsequent generation
to reprogram developmental and cellular features. This short review describes
current knowledge on the potential impact of epigenetic processes activated by
environmental factors on the inheritance of neurobiological disease risk. In
addition, the potential adaptive value of epigenetic inheritance, and relevant
current and future questions are discussed.
PMID- 24353209
TI - Neuromodulators, stress and plasticity: a role for endocannabinoid signalling.
AB - Any unanticipated threat to survival triggers an immediate sequence of events in
the brain that culminate in a coordinated neural, endocrine and behavioural
response. There is increasing evidence that stress itself modifies neural
circuits. In other words, neural stress circuits learn from stress. This self
teaching is surprising as one might expect these essential circuits to be hard
wired. Our recent findings, however, indicate that repeated homotypic stress in
rats causes functional changes in neural circuitry in the hypothalamus. In
particular, we focus on signalling via endocannabinoids and describe plasticity
in this system that impacts fast retrograde signalling at synapses on to the
stress command neurons in the brain. Interestingly, this plasticity appears to be
limited to early adolescence, hinting at unique modes of control of neural
circuits by stress during different developmental stages.
PMID- 24353211
TI - Cell signalling mechanisms for insect stress tolerance.
AB - Insects successfully occupy most environmental niches and this success depends on
surviving a broad range of environmental stressors including temperature,
desiccation, xenobiotic, osmotic and infection stress. Epithelial tissues play
key roles as barriers between the external and internal environments and
therefore maintain homeostasis and organismal tolerance to multiple stressors. As
such, the crucial role of epithelia in organismal stress tolerance cannot be
underestimated. At a molecular level, multiple cell-specific signalling pathways
including cyclic cAMP, cyclic cGMP and calcium modulate tissue, and hence,
organismal responses to stress. Thus, epithelial cell-specific signal
transduction can be usefully studied to determine the molecular mechanisms of
organismal stress tolerance in vivo. This review will explore cell signalling
modulation of stress tolerance in insects by focusing on cell signalling in a
fluid transporting epithelium--the Malpighian tubule. Manipulation of specific
genes and signalling pathways in only defined tubule cell types can influence the
survival outcome in response to multiple environmental stressors including
desiccation, immune, salt (ionic) and oxidative stress, suggesting that studies
in the genetic model Drosophila melanogaster may reveal novel pathways required
for stress tolerance.
PMID- 24353210
TI - Promoting longevity by maintaining metabolic and proliferative homeostasis.
AB - Aging is characterized by a widespread loss of homeostasis in biological systems.
An important part of this decline is caused by age-related deregulation of
regulatory processes that coordinate cellular responses to changing environmental
conditions, maintaining cell and tissue function. Studies in genetically
accessible model organisms have made significant progress in elucidating the
function of such regulatory processes and the consequences of their deregulation
for tissue function and longevity. Here, we review such studies, focusing on the
characterization of processes that maintain metabolic and proliferative
homeostasis in the fruitfly Drosophila melanogaster. The primary regulatory axis
addressed in these studies is the interaction between signaling pathways that
govern the response to oxidative stress, and signaling pathways that regulate
cellular metabolism and growth. The interaction between these pathways has
important consequences for animal physiology, and its deregulation in the aging
organism is a major cause for increased mortality. Importantly, protocols to tune
such interactions genetically to improve homeostasis and extend lifespan have
been established by work in flies. This includes modulation of signaling pathway
activity in specific tissues, including adipose tissue and insulin-producing
tissues, as well as in specific cell types, such as stem cells of the fly
intestine.
PMID- 24353212
TI - Transcellular chaperone signaling: an organismal strategy for integrated cell
stress responses.
AB - The ability of each cell within a metazoan to adapt to and survive environmental
and physiological stress requires cellular stress-response mechanisms, such as
the heat shock response (HSR). Recent advances reveal that cellular proteostasis
and stress responses in metazoans are regulated by multiple layers of
intercellular communication. This ensures that an imbalance of proteostasis that
occurs within any single tissue 'at risk' is protected by a compensatory
activation of a stress response in adjacent tissues that confers a community
protective response. While each cell expresses the machinery for heat shock (HS)
gene expression, the HSR is regulated cell non-autonomously in multicellular
organisms, by neuronal signaling to the somatic tissues, and by transcellular
chaperone signaling between somatic tissues and from somatic tissues to neurons.
These cell non-autonomous processes ensure that the organismal HSR is
orchestrated across multiple tissues and that transmission of stress signals
between tissues can also override the neuronal control to reset cell- and tissue
specific proteostasis. Here, we discuss emerging concepts and insights into the
complex cell non-autonomous mechanisms that control stress responses in metazoans
and highlight the importance of intercellular communication for proteostasis
maintenance in multicellular organisms.
PMID- 24353213
TI - The mitochondrial unfolded protein response, a conserved stress response pathway
with implications in health and disease.
AB - The ability to respond to various intracellular and/or extracellular stresses
allows the organism to adapt to changing environmental conditions and drives
evolution. It is now well accepted that a progressive decline of the efficiency
of stress response pathways occurs with aging. In this context, a correct
proteostasis is essential for the functionality of the cell, and its dysfunction
has been associated with protein aggregation and age-related degenerative
diseases. Complex response mechanisms have evolved to deal with unfolded protein
stress in different subcellular compartments and their moderate activation
translates into positive effects on health. In this review, we focus on the
mitochondrial unfolded protein response (UPR(mt)), a response to proteotoxic
stress specifically in mitochondria, an organelle with a wide array of
fundamental functions, most notably the harvesting of energy from food and the
control of cell death. We compare UPR(mt) with the extensively characterized
cytosolic heat shock response (HSR) and the unfolded protein response in
endoplasmic reticulum (UPR(ER)), and discuss the current knowledge about UPR(mt)
signaling pathways as well as their potential involvement in physiology.
PMID- 24353216
TI - Complex band structure eigenvalue method adapted to Floquet systems: topological
superconducting wires as a case study.
AB - For systems that can be modeled as a single-particle lattice extended along a
privileged direction, such as, for example, quantum wires, the so-called
eigenvalue method provides full information about the propagating and evanescent
modes as a function of energy. This complex band structure method can be applied
either to lattices consisting of an infinite succession of interconnected layers
described by the same local Hamiltonian or to superlattices: systems in which the
spatial periodicity involves more than one layer. Here, for time-dependent
systems subject to a periodic driving, we present an adapted version of the
superlattice scheme capable of obtaining the Floquet states and the Floquet
quasienergy spectrum. Within this scheme the time periodicity is treated as
existing along a spatial dimension added to the original system. The solutions at
a single energy for the enlarged artificial system provide the solutions of the
original Floquet problem. The method is suited for arbitrary periodic
excitations, including strong and anharmonic drivings. We illustrate the
capabilities of the methods for both time-independent and time-dependent systems
by discussing: (a) topological superconductors in multimode quantum wires with
spin-orbit interaction and (b) microwave driven quantum dots in contact with a
topological superconductor.
PMID- 24353215
TI - Management of postoperative atrial fibrillation and subsequent outcomes in
contemporary patients undergoing cardiac surgery: insights from the Society of
Thoracic Surgeons CAPS-Care Atrial Fibrillation Registry.
AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is a well-recognized
complication of cardiac surgery; however, its management remains a challenge, and
the implementation and outcomes of various strategies in clinical practice remain
unclear. HYPOTHESIS: We hypothesize that treatment for POAF is variable, and that
it is associated with particular morbidity and mortality following cardiac
surgery. METHODS: We compared patient characteristics, operative procedures,
postoperative management, and outcomes between patients with and without POAF
following coronary artery bypass grafting (CABG) in the Society of Thoracic
Surgeons multicenter Contemporary Analysis of Perioperative Cardiovascular
Surgical Care (CAPS-Care) registry (2004-2005). RESULTS: Of 2390 patients who
underwent CABG, 676 (28%) had POAF. Compared with patients without POAF, those
with POAF were older (median age 74 vs 71 years, P<0.0001) and more likely to
have hypertension (86% vs 83%, P=0.04) and impaired renal function (median
estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2, P=0.0001). A
majority of patients with POAF were treated with amiodarone (77%) and beta
blockers (68%); few (9.9%) underwent cardioversion. Patients with POAF were more
likely to experience complications (57% vs 41%, P<0.0001), including acute limb
ischemia (1.0% vs 0.4%, P=0.03), stroke (4.0% vs 1.9%, P=0.002), and reoperation
(13% vs 7.9%, P<0.0001). Length of stay (median 8 days vs 6 days, P<0.0001), in
hospital mortality (6.8% vs 3.7%, P=0.001), and 30-day mortality (7.8 vs 3.9,
P<0.0001) were all worse for patients with POAF. In adjusted analyses, POAF
remained associated with increased length of stay following surgery (adjusted
ratio of the mean: 1.27, 95% confidence interval: 1.2-1.34, P<0.0001).
CONCLUSIONS: Postoperative AF is common following CABG, and such patients
continue to have higher rates of postoperative complications. Postoperative AF is
significantly associated with increased length of stay following surgery.
PMID- 24353218
TI - Controversy still swirls around FDA user fees: since 1992, the prescription drug
user fee act and reauthorizations have sped up new drug approvals--but does speed
equal safety?
PMID- 24353214
TI - Stress adaptation in a pathogenic fungus.
AB - Candida albicans is a major fungal pathogen of humans. This yeast is carried by
many individuals as a harmless commensal, but when immune defences are perturbed
it causes mucosal infections (thrush). Additionally, when the immune system
becomes severely compromised, C. albicans often causes life-threatening systemic
infections. A battery of virulence factors and fitness attributes promote the
pathogenicity of C. albicans. Fitness attributes include robust responses to
local environmental stresses, the inactivation of which attenuates virulence.
Stress signalling pathways in C. albicans include evolutionarily conserved
modules. However, there has been rewiring of some stress regulatory circuitry
such that the roles of a number of regulators in C. albicans have diverged
relative to the benign model yeasts Saccharomyces cerevisiae and
Schizosaccharomyces pombe. This reflects the specific evolution of C. albicans as
an opportunistic pathogen obligately associated with warm-blooded animals,
compared with other yeasts that are found across diverse environmental niches.
Our understanding of C. albicans stress signalling is based primarily on the in
vitro responses of glucose-grown cells to individual stresses. However, in vivo
this pathogen occupies complex and dynamic host niches characterised by
alternative carbon sources and simultaneous exposure to combinations of stresses
(rather than individual stresses). It has become apparent that changes in carbon
source strongly influence stress resistance, and that some combinatorial stresses
exert non-additive effects upon C. albicans. These effects, which are relevant to
fungus-host interactions during disease progression, are mediated by multiple
mechanisms that include signalling and chemical crosstalk, stress pathway
interference and a biological transistor.
PMID- 24353220
TI - Have the Annals editors added value?
PMID- 24353217
TI - Pharmacological interventions for drug-using offenders.
AB - BACKGROUND: The review represents one in a family of four reviews focusing on a
range of different interventions for drug-using offenders. This specific review
considers pharmacological interventions aimed at reducing drug use and/or
criminal activity for illicit drug-using offenders. OBJECTIVES: To assess the
effectiveness of pharmacological interventions for drug-using offenders in
reducing criminal activity and/or drug use. SEARCH METHODS: Fourteen electronic
bibliographic databases (searched between 2004 and 21 March 2013) and five
additional Web resources (searched between 2004 and 11 November 2011) were
searched. Experts in the field were contacted for further information. SELECTION
CRITERIA: Randomised controlled trials assessing the efficacy of any
pharmacological interventions for reducing, eliminating or preventing relapse in
drug-using offenders were included. Data on the cost and cost-effectiveness of
interventions were reported. DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures as expected by The Cochrane Collaboration. MAIN
RESULTS: A total of 76 trials across the four reviews were identified. After a
process of prescreening had been completed, 17 trials were judged to meet the
inclusion criteria for this specific review (six of the 17 trials are awaiting
classification for the review). The remaining 11 trials contained a total of
2,678 participants. Nine of the eleven studies used samples with a majority of
men. The interventions (buprenorphine, methadone and naltrexone) were compared to
non pharmacological treatments (e.g., counselling) and other pharmacological
drugs. The methodological trial quality was poorly described, and most studies
were rated as 'unclear' by the reviewers. The biggest threats to risk of bias
were generated through blinding (performance and detection bias) and incomplete
outcome data (attrition bias). When combined, the results suggest that
pharmacological interventions do significantly reduce subsequent drug use using
biological measures, (three studies, 300 participants, RR 0.71 (95% CI 0.52 to
0.97)), self report dichotomous data (three studies, 317 participants, RR 0.42,
(95% CI 0.22 to 0.81)) and continuous measures (one study, MD -59.66 (95% CI
120.60 to 1.28)) . In the subgroups analysis for community setting, (two studies,
99 participants: RR 0.62 (95% CI 0.35 to 1.09)) and for secure establishment
setting, (one study, 201 participants: RR 0.76 (95% CI 0.52 to 1.10)), the
results are no longer statistically significant. Criminal activity was
significantly reduced favouring the dichotomous measures of re arrest, (one
study, 62 participants, RR 0.60 (95% CI 0.32 to 1.14)), re-incarceration, (three
studies, 142 participants, RR 0.33 (95% CI 0.19 to 0.56)) and continuous measures
(one study, 51 participants, MD -74.21 (95% CI -133.53 to -14.89)). Findings on
the effects of individual pharmacological interventions on drug use and criminal
activity show mixed results. Buprenorphine in comparison to a non pharmacological
treatment seemed to favour buprenorphine but not significantly with self report
drug use, (one study, 36 participants, RR 0.58 (95% CI 0.25 to 1.35)). Methadone
and cognitive behavioural skills in comparison to standard psychiatric services,
did show a significant reduction for self report dichotomous drug use (one study,
253 participants, RR 0.43 (95% CI 0.33 to 0.56)) but not for self report
continuous data (one study 51 participants) MD -0.52 (95% CI -1.09 to 0.05)), or
re incarceration RR 1.23 (95% CI 0.53 to 2.87)). Naltrexone was favoured
significantly over routine parole and probation for re incarceration (two studies
114 participants, RR 0.36 (95% CI 0.19 to 0.69)) but no data was available on
drug use. Finally, we compared each pharmacological treatment to another. In each
case we compared methadone to: buprenorphine, diamorphine and naltrexone. No
significant differences were displayed for either treatment for self report
dichotomous drug use (one study, 193 participants RR 1.23 (95% CI 0.86 to 1.76)),
continuous measures of drug use MD 0.70 (95% CI -5.33 to 6.73) or criminal
activity RR 1.25 (95% CI 0.83 to 1.88)) between methadone and buprenorphine.
Similiar results were found for comparisons with Diamorphine with no significant
differences between the drugs for self report dichotomous drug use for arrest
(one study, 825 participants RR 1.25 (95% CI 1.03-1.51)) or Naltrexone for
dichotomous measures of re incarceration (one study, 44 participants, RR 1.10
(95% CI 0.37 to 3.26)), and continuous outcome measure of crime MD -0.50 (95% CI
8.04 to 7.04)) or self report drug use MD 4.60 (95% CI -3.54 to 12.74)). AUTHORS'
CONCLUSIONS: Pharmacological interventions for drug-using offenders do appear to
reduce overall subsequent drug use and criminal activity (but to a lesser
extent). No statistically significant differences were displayed by treatment
setting. Individual differences are displayed between the three pharmacological
interventions (buprenorphine, methadone and naltrexone) when compared to a non
pharmacological intervention, but not when compared to each other. Caution should
be taken when interpreting these findings, as the conclusions are based on a
small number of trials, and generalisation of these study findings should be
limited mainly to male adult offenders. Additionally, many studies were rated at
high risk of bias because trial information was inadequately described.
PMID- 24353221
TI - Specific and nonspecific psychological interventions for PTSD symptoms: a meta
analysis with problem complexity as a moderator.
AB - CONTEXT: The necessity of specific intervention components for the successful
treatment of patients with posttraumatic stress disorder is the subject of
controversy. OBJECTIVE: To investigate the complexity of clinical problems as a
moderator of relative effects between specific and nonspecific psychological
interventions. METHODS: We included 18 randomized controlled trials, directly
comparing specific and nonspecific psychological interventions. We conducted
moderator analyses, including the complexity of clinical problems as predictor.
RESULTS: Our results have confirmed the moderate superiority of specific over
nonspecific psychological interventions; however, the superiority was small in
studies with complex clinical problems and large in studies with noncomplex
clinical problems. CONCLUSIONS: For patients with complex clinical problems, our
results suggest that particular nonspecific psychological interventions may be
offered as an alternative to specific psychological interventions. In contrast,
for patients with noncomplex clinical problems, specific psychological
interventions are the best treatment option.
PMID- 24353222
TI - Predicting the activity and toxicity of new psychoactive substances: a
pharmaceutical industry perspective.
AB - Predicting the effect that new compounds might have when administered to human
beings is a common desire shared by researchers in the pharmaceutical industry
and those interested in psychoactive compounds (illicit or otherwise). The
experience of the pharmaceutical industry is that making such predictions at a
usefully accurate level is not only difficult but that even when billions of
dollars are spent to ensure that only compounds likely to have a desired effect
without unacceptable side-effects are dosed to humans in clinical trials, they
fail in more than 90% of cases. A range of experimental and computational
techniques is used and they are placed in their context in this paper. The
particular roles played by computational techniques and their limitations are
highlighted; these techniques are used primarily to reduce the number of
experiments that must be performed but cannot replace those experiments.
PMID- 24353225
TI - Bilirubin in a new light.
PMID- 24353226
TI - A directional entropic force approach to assemble anisotropic nanoparticles into
superlattices.
PMID- 24353227
TI - Utilizing combinatorial chemistry and rational design: peptidic tweezers with
nanomolar affinity to DNA can be transformed into efficient vectors for gene
delivery by addition of a lipophilic tail.
PMID- 24353228
TI - Noninvasive measurement of the mechanical force generated by motor protein EF-G
during ribosome translocation.
PMID- 24353229
TI - Preparation of small-molecule microarrays by trans-cyclooctene tetrazine ligation
and their application in the high-throughput screening of protein-protein
interaction inhibitors of bromodomains.
PMID- 24353230
TI - Genetic incorporation of multiple unnatural amino acids into proteins in
mammalian cells.
PMID- 24353231
TI - Conjugate-base-stabilized Bronsted acids as asymmetric catalysts:
enantioselective Povarov reactions with secondary aromatic amines.
PMID- 24353233
TI - Iron pincer complex catalyzed, environmentally benign, E-selective semi
hydrogenation of alkynes.
PMID- 24353232
TI - Palladium-catalyzed completely linear-selective Negishi cross-coupling of
allylzinc halides with aryl and vinyl electrophiles.
PMID- 24353234
TI - Surfactant-type Bronsted acid catalyzed stereoselective synthesis of trans-3
alkenyl indazoles from triazenylaryl allylic alcohols in water.
PMID- 24353235
TI - Dependence of the properties of dihydroindenofluorene derivatives on positional
isomerism: influence of the ring bridging.
PMID- 24353236
TI - Template-assisted self-assembly: alignment, placement, and arrangement of two
dimensional mesostructured DNA-silica platelets.
PMID- 24353237
TI - Catalytic asymmetric hydrogenation of alpha-CF3- or beta-CF3-substituted acrylic
acids using rhodium(I) complexes with a combination of chiral and achiral
ligands.
PMID- 24353238
TI - Palladium-catalyzed oxidative carbonylation of the alkenyl C-H bonds of enamides:
synthesis of 1,3-oxazin-6-ones.
PMID- 24353239
TI - Palladium-catalyzed aerobic domino oxidative carbocyclization-alkynylation of
allenynes.
PMID- 24353240
TI - Identification of molecular species of cholesteryl ester hydroperoxides in very
low-density and intermediate-density lipoproteins.
AB - BACKGROUND: Oxidation of lipoproteins is thought to play a crucial role in
atherogenesis. Role for triglyceride-rich lipoproteins in atherogenesis is
unclear. Thus, we aimed to investigate whether cholesteryl ester hydroperoxides
(CEOOH) are present in very low-density lipoproteins (VLDL) and intermediate
density lipoproteins (IDL) by using highly sensitive liquid chromatography/mass
spectrometry. METHODS: Total lipids were extracted from the plasma of healthy
donors (n = 6) and their fractions of VLDL and IDL. Additional three plasma
samples were analysed freshly for CEOOH. Detection and identification of CEOOH
was conducted by liquid chromatography/LTQ ion trap mass spectrometry/Orbitrap
high mass accuracy mass spectrometry. Authentic standards of CEOOH were used for
unequivocal identification on the basis of their mass spectra. RESULTS: We
identified six molecular CEOOH species overall, namely, Ch18:1-OOH, Ch18:2-OOH,
Ch18:3-OOH, Ch20:4-OOH, Ch20:5-OOH and Ch22:6-OOH. Of them, Ch18:2-OOH, Ch20:5
OOH, Ch20:4-OOH and Ch22:6-OOH were detected in all IDL samples, while only
Ch20:4-OOH was detected in all VLDL samples. All of CEOOH species except for
Ch18:3-OOH were detected in plasma, with constant detection of Ch20:5-OOH, and
Ch22:6-OOH in all plasma samples. CONCLUSION: The presence of CEOOH species in
VLDL and IDL was confirmed with the analytical sensitivity of 0.1 pmol, showing
the constant appearance of more CEOOH species in IDL than VLDL. This finding
might add biochemical evidences of atherogenicity of these lipoproteins. Clinical
utility of measuring CEOOH level in these lipoproteins need to be investigated
for the risk assessment of the cardiovascular disease.
PMID- 24353241
TI - Correlations between apparent diffusion coefficient values of invasive ductal
carcinoma and pathologic factors on diffusion-weighted MRI at 3.0 Tesla.
AB - PURPOSE: To investigate correlations between apparent diffusion coefficient (ADC)
values of invasive ductal carcinoma (IDC) and pathologic factors on diffusion
weighted MRI. We measured the ADC values of IDC of the breast and analyzed
correlations between ADC values and factors such as tumor size, axillary lymph
node status, histologic grade, estrogen receptor, progesterone receptor, and
human epithelial growth factor 2 (HER2) using diffusion-weighted MRI at 3.0 Tesla
(T). MATERIALS AND METHODS: We examined 110 patients with pathologically
confirmed IDC using diffusion-weighted MRI at 3.0T. The ADC values of breast
cancer were calculated using two b factors (0 and 1000 s/mm(2)). The relationship
between ADC values and tumor size, histologic grade, axillary lymph node status,
hormonal receptors, and HER2 were analyzed. RESULTS: The mean ADC value of IDC (n
= 110) was 0.88 +/- 0.15 * 10(-2) mm(2)/s. Tumors were subgrouped according to
size (<2 cm, 2-5 cm, and >=5 cm). Multiple comparisons within subgroups according
to size showed that the ADC values for the three tumor size groups were
significantly different (correlation coefficient = -0.007). The mean apparent
diffusion coefficient of HER2-positive IDC was significantly higher than that of
HER2-negative invasive ductal carcinoma (correlation coefficient = 0.218).
CONCLUSION: ADC values of IDC were significantly correlated with tumor size and
HER2 status.
PMID- 24353242
TI - Recall intervals for oral health in primary care patients.
AB - BACKGROUND: The frequency with which patients should attend for a dental check-up
and the potential effects on oral health of altering recall intervals between
check-ups have been the subject of ongoing international debate in recent
decades. Although recommendations regarding optimal recall intervals vary between
countries and dental healthcare systems, six-monthly dental check-ups have
traditionally been advocated by general dental practitioners in many developed
countries.This is an update of a Cochrane review first published in 2005, and
previously updated in 2007. OBJECTIVES: To determine the beneficial and harmful
effects of different fixed recall intervals (for example six months versus 12
months) for the following different types of dental check-up: a) clinical
examination only; b) clinical examination plus scale and polish; c) clinical
examination plus preventive advice; d) clinical examination plus preventive
advice plus scale and polish.To determine the relative beneficial and harmful
effects between any of these different types of dental check-up at the same fixed
recall interval.To compare the beneficial and harmful effects of recall intervals
based on clinicians' assessment of patients' disease risk with fixed recall
intervals.To compare the beneficial and harmful effects of no recall
interval/patient driven attendance (which may be symptomatic) with fixed recall
intervals. SEARCH METHODS: The following electronic databases were searched: the
Cochrane Oral Health Group's Trials Register (to 27 September 2013), the Cochrane
Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue
9), MEDLINE via OVID (1946 to 27 September 2013) and EMBASE via OVID (1980 to 27
September 2013). We searched the US National Institutes of Health Trials Register
(http://clinicaltrials.gov) and the WHO International Clinical Trials Registry
Platform (http://www.who.int/ictrp/en/) for ongoing trials. Reference lists from
relevant articles were scanned and the authors of some papers were contacted to
identify further trials and obtain additional information. We did not apply any
restrictions regarding language or date of publication when searching the
electronic databases. SELECTION CRITERIA: We included randomised controlled
trials (RCTs) assessing the effects of different dental recall intervals. DATA
COLLECTION AND ANALYSIS: Two review authors independently assessed the search
results against the inclusion criteria of the review, extracted data and carried
out risk of bias assessment. We contacted study authors for clarification or
further information where necessary and feasible. If we had found more than one
study with similar comparisons reporting the same outcomes, we would have
combined the studies in a meta-analysis using a random-effects model if there
were at least four studies, or a fixed-effect model if there were less than four
studies. We expressed the estimate of effect as mean difference with 95%
confidence intervals (CIs) for continuous outcomes. We would have used risk
ratios with 95% CI for any dichotomous outcomes. MAIN RESULTS: We included one
study that analysed 185 participants. The study compared the effects of a
clinical examination every 12 months with a clinical examination every 24 months
on the outcomes of caries (decayed, missing, filled surfaces (dmfs/DMFS)
increment) and economic cost outcomes (total time used per person). As the study
was at high risk of bias, had a small sample size and only included low-risk
participants, we rated the quality of the body of evidence for these outcomes as
very low.For three to five-year olds with primary teeth, the mean difference (MD)
in dmfs increment was -0.90 (95% CI -1.96 to 0.16) in favour of 12-month recall.
For 16 to 20-year olds with permanent teeth, the MD in DMFS increment was -0.86
(95% CI -1.75 to 0.03) also in favour of 12-month recall. There is insufficient
evidence to determine whether 12 or 24-month recall with clinical examination
results in better caries outcomes.For three to five-year olds with primary teeth,
the MD in time used by each participant was 10 minutes (95% CI -6.7 to 26.7) in
favour of 24-month recall. For 16 to 20-year olds with permanent teeth, the MD
was 23.7 minutes (95% CI 4.12 to 43.28) also in favour of 24-month recall. This
single study at high risk of bias represents insufficient evidence to determine
whether 12 or 24-month recall with clinical examination results in better
time/cost outcomes. AUTHORS' CONCLUSIONS: There is a very low quality body of
evidence from one RCT which is insufficient to draw any conclusions regarding the
potential beneficial and harmful effects of altering the recall interval between
dental check-ups. There is no evidence to support or refute the practice of
encouraging patients to attend for dental check-ups at six-monthly intervals. It
is important that high quality RCTs are conducted for the outcomes listed in this
review in order to address the objectives of this review.
PMID- 24353243
TI - Hemodynamics in two tandem aneurysms treated with flow diverters.
AB - The purpose of this study was to investigate whether the occlusion time of
cerebral aneurysms treated with flow diverters depends on the hemodynamic
conditions created immediately after treatment. A case study of a pair of tandem
intracranial aneurysms that were treated with flow-diverting devices and occluded
at different times was carried out. A patient-specific computational fluid
dynamics model was constructed from 3D rotational angiography images. Blood flow
simulations were carried out under pulsatile physiologic conditions, and
hemodynamic variables before and after deployment of the flow-diverting devices
were quantified and compared. The flow-diverting devices reduced aneurysm inflow
rates, intra-aneurysmal flow velocities, shear rates, and wall shear stresses.
The flow patterns after flow modulation by the flow diverters were smoother and
with less swirling. The reductions in hemodynamic quantities depended on the
aneurysm and parent artery and were larger in the aneurysm that occluded faster.
The results of this case study suggest that the larger the reduction in the
hemodynamic variables considered, the shorter the time it takes for the aneurysm
to thrombose. This result can help us better define the goal of these
interventions.
PMID- 24353245
TI - It's time to make changes: modulation of root system architecture by nutrient
signals.
AB - Root growth and development are of outstanding importance for the plant's ability
to acquire water and nutrients from different soil horizons. To cope with
fluctuating nutrient availabilities, plants integrate systemic signals pertaining
to their nutritional status into developmental pathways that regulate the spatial
arrangement of roots. Changes in the plant nutritional status and external
nutrient supply modulate root system architecture (RSA) over time and determine
the degree of root plasticity which is based on variations in the number,
extension, placement, and growth direction of individual components of the root
system. Roots also sense the local availability of some nutrients, thereby
leading to nutrient-specific modifications in RSA, that result from the
integration of systemic and local signals into the root developmental programme
at specific steps. An in silico analysis of nutrient-responsive genes involved in
root development showed that the majority of these specifically responded to the
deficiency of individual nutrients while a minority responded to more than one
nutrient deficiency. Such an analysis provides an interesting starting point for
the identification of the molecular players underlying the sensing and
transduction of the nutrient signals that mediate changes in the development and
architecture of root systems.
PMID- 24353246
TI - Selective protein degradation: a rheostat to modulate cell-cycle phase
transitions.
AB - Plant growth control has become a major focus due to economic reasons and results
from a balance of cell proliferation in meristems and cell elongation that occurs
during differentiation. Research on plant cell proliferation over the last two
decades has revealed that the basic cell-cycle machinery is conserved between
human and plants, although specificities exist. While many regulatory circuits
control each step of the cell cycle, the ubiquitin proteasome system (UPS)
appears in fungi and metazoans as a major player. In particular, the UPS promotes
irreversible proteolysis of a set of regulatory proteins absolutely required for
cell-cycle phase transitions. Not unexpectedly, work over the last decade has
brought the UPS to the forefront of plant cell-cycle research. In this review, we
will summarize our knowledge of the function of the UPS in the mitotic cycle and
in endoreduplication, and also in meiosis in higher plants.
PMID- 24353247
TI - The anatomical basis for wrinkles.
AB - BACKGROUND: Light and electron microscopy have not identified a distinct
anatomical structure associated with either skin wrinkles or creases, and a
histological difference between wrinkled and adjacent skin has not been
identified. OBJECTIVES: The authors investigate whether facial wrinkles are
related to underlying lymphatic vessels and perilymphatic fat. METHODS: Lymphatic
vessels with a specialized tube of perilymphatic fat were identified beneath
palmar creases. Sections of skin, adipose tissue, and muscle were harvested from
each of 13 cadavers. Three sites were investigated: the transverse forehead
crease, lateral orbicularis oculi wrinkle (crow's feet), and the nasojugal
crease. The tissue was paraffin embedded and processed. Two-step indirect
immunohistochemistry was performed, and images were examined using laser confocal
microscopy. Measurements were taken with software. RESULTS: Every wrinkle
examined was found above and within +/-1 mm of a major lymphatic vessel and its
surrounding tube of adipose tissue. The results satisfied our null hypothesis and
were statistically significant. Lymphatic vessels were identified by positive
immunofluorescence as well as histological criteria. These findings have been
further validated by fluorochrome tracer studies. CONCLUSIONS: An anatomical
basis for wrinkles was identified among the specimens studied. Lymphatic vessels,
along with the surrounding distinct perilymphatic fat, traveled directly beneath
wrinkles and creases. Lymphatic dysregulation leads to inflammation, scarring,
and fibrosis, but inadvertent injection of these vessels can be avoided with
anatomical knowledge.
PMID- 24353250
TI - The effect of impaired 50-gram oral glucose challenge test on fetal abdominal
wall thickness.
AB - BACKGROUND: Patients with impaired 50-g oral glucose challenge test (OGCT) have
not been investigated for fetal anterior abdominal wall thickness until now. We
aimed to investigate patients with impaired 50-g OGCT, but not gestational
diabetes and match them with healthy uneventful pregnant participants for
anterior abdominal wall thickness, estimated fetal weight, fetal gender,
biparietal diameter, femur length and abdominal circumference. METHODS: A total
of 99 pregnant women between 26 and 28 weeks of gestation were enrolled in the
study. These patients were divided into two groups according to their 50-g OGCT
results. Fifty-one pregnant women with uncomplicated healthy singleton
pregnancies constituted our control group, and 48 singleton pregnant women with
impaired 50-g OGCT but normal 100-g oral glucose tolerance test constituted our
study group. RESULTS: We detected statistically significant high body mass index
in impaired 50-g glucose test group. Biparietal diameter, femur length, abdominal
circumference and estimated fetal weight values were not significantly different
between groups; however, anterior abdominal wall thickness value was
significantly width in impaired 50-g glucose test group. Moreover, there were no
statistically significant differences between two groups for gender of fetuses.
CONCLUSION: Impaired 50-g glucose test in pregnancy is related not only to
increased maternal body mass index but also to fetal fat distribution. Although
fetal abdominal circumference measurement and estimated fetal weight were not
different between study and control group, increased anterior abdominal wall
thickness can be detected in impaired 50-g OGCT group.
PMID- 24353248
TI - Contrast-enhanced microCT (EPIC-MUCT) ex vivo applied to the mouse and human jaw
joint.
AB - OBJECTIVES: The temporomandibular joint (TMJ) is susceptive to the development of
osteoarthritis (OA). More detailed knowledge of its development is essential to
improve our insight into TMJ-OA. It is imperative to have a standardized reliable
three-dimensional (3D) imaging method that allows for detailed assessment of both
bone and cartilage in healthy and diseased joints. We aimed to determine the
applicability of a contrast-enhanced microCT (uCT) technique for ex vivo research
of mouse and human TMJs. METHODS: Equilibrium partitioning of an ionic contrast
agent via uCT (EPIC-uCT) was previously applied for cartilage assessment in the
knee joint. The method was ex vivo, applied to the mouse TMJ and adapted for the
human TMJ. RESULTS: EPIC-uCT (30-min immersion time) was applied to mouse
mandibular condyles, and 3D imaging revealed an average cartilage thickness of
110 +/- 16 um. These measurements via EPIC-uCT were similar to the
histomorphometric measures (113 +/- 19 um). For human healthy OA-affected TMJ
samples, the protocol was adjusted to an immersion time of 1 h. 3D imaging
revealed a significant thicker cartilage layer in joints with early signs of OA
compared with healthy joints (414.2 +/- 122.6 and 239.7 +/- 50.5 um,
respectively). A subsequent significant thinner layer was found in human joints
with late signs of OA (197.4 +/- 159.7 um). CONCLUSIONS: The EPIC-uCT technique
is effective for the ex vivo assessment of 3D cartilage morphology in the mouse
as well as human TMJ and allows bone-cartilage interaction research in TMJ-OA.
PMID- 24353251
TI - A comparison of material characterizations in frequently used constitutive models
of ligaments.
AB - Longitudinal tensile and simple shear stress-strain curves of human medial
collateral ligaments (MCL) were fitted by six frequently used constitutive
relations of ligaments using two different fitting methods for determining which
was the best fitting method and the most preferable constitutive model for
describing the ligament properties. According to the results of fitting goodness,
two typical constitutive models were further analyzed by FEM to investigate the
effect of the variation in MCL constitutive models under some physiological loads
(i.e., 4.5 Nm external tibial and 10 Nm valgus tibial torques). It was found that
different fitting methods induced great variations in describing the simple shear
behavior whereas no obvious difference in the longitudinal tensile behavior. The
most accurate description of both the longitudinal tensile and simple shear
behaviors was obtained from the constitutive model with ground substance defined
by an exponential function when the parameters were fitted by the two test data,
respectively. Although the distributions of maximal principal stress were almost
the same, the variation in MCL constitutive models affected the highest value of
the stress greatly when MCL was under the complex physiological loads.
PMID- 24353252
TI - First trimester detection of trisomy 16 using combined biochemical and ultrasound
screening.
PMID- 24353253
TI - Urine C-peptide creatinine ratio can be used to assess insulin resistance and
insulin production in people without diabetes: an observational study.
AB - OBJECTIVES: The current assessment of insulin resistance (IR) in epidemiology
studies relies on the blood measurement of C-peptide or insulin. A urine C
peptide creatinine ratio (UCPCR) can be posted from home unaided. It is validated
against serum measures of the insulin in people with diabetes. We tested whether
UCPCR could be a surrogate measure of IR by examining the correlation of UCPCR
with serum insulin, C-peptide and HOMA2 (Homeostasis Model Assessment 2)-IR in
participants without diabetes and with chronic kidney disease (CKD). DESIGN:
Observational study. SETTING: Single-centre clinical research facility.
PARTICIPANTS: 37 healthy volunteers and 30 patients with CKD (glomerular
filtration rate 15-60) were recruited. PRIMARY AND SECONDARY ENDPOINTS: Serum
insulin, C-peptide and glucose at fasting (0), 30, 60, 90 and 120 min were
measured during an oral glucose tolerance test (OGTT). Second-void fasting UCPCR
and 120 min post-OGTT UCPCR were collected. HOMA2-IR was calculated using fasting
insulin and glucose. The associations between UCPCR and serum measures were
assessed using Spearman's correlations. RESULTS: In healthy volunteers, fasting
second-void UCPCR strongly correlated with serum insulin (rs=0.69, p<0.0001), C
peptide (rs=0.73, p<0.0001) and HOMA2-IR (rs=-0.69, p<0.0001). 120 min post-OGTT
UCPCR correlated strongly with C-peptide and insulin area under the curve. In
patients with CKD, UCPCR did not correlate with serum C-peptide, insulin or HOMA2
IR. CONCLUSIONS: In participants with normal renal function, UCPCR may be a
simple, practical method for the assessment of IR in epidemiology studies.
PMID- 24353254
TI - Incidental findings of elevated random plasma glucose in the ED as a prompt for
outpatient diabetes screening: a retrospective study.
AB - OBJECTIVE: To determine whether random plasma glucose (RPG) collected from
patients without known impaired glucose metabolism (IGM) in the emergency
department (ED) is a useful screen for diabetes or prediabetes. DESIGN:
Retrospective cohort study. SETTING: ED of a Canadian teaching hospital over 1
month. PARTICIPANTS: Adult patients in ED with RPG over 7 mmol/L were recruited
for participation. Exclusion criteria included known diabetes, hospital admission
and inability to consent. Participants were contacted by mail, encouraged to
follow-up with their family physician (FP) for further testing and subsequently
interviewed. OUTCOME MEASURES: The primary outcome measure was the proportion of
patients in the ED with RPG over 7 mmol/L and no previous diagnosis of IGM who
were diagnosed with diabetes or prediabetes after secondary testing by FP with
oral glucose tolerance test or fasting plasma glucose (FPG). Secondary outcomes
included patient characteristics (age, gender, body mass index and language) and
(2) compliance with advice to seek an appropriate follow-up care. RESULTS: RPG
was drawn on approximately one-third (33%, n=1149) of the 3470 patients in the ED
in March 2010. RPG over 7 mmol/L was detected in 24% (n=278) of patients, and
after first telephone follow-up, 32% (n=88/278) met the inclusion criteria and
were advised to seek confirmatory testing. 41% (n=114/278) of patients were
excluded for known diabetes. 73% of patients contacted (n=64/88) followed up with
their FP. 12.5% (n=11/88) of patients had abnormal FPG, and of these 11%
(n=10/88) were encouraged to initiate lifestyle modifications and 1% (n=1/88) was
started on an oral hypoglycaemic agent. For 7% (n=6/88) of patients, FP's
declined to do follow-up fasting blood work. CONCLUSIONS: Elevated RPG in the ED
is useful for identification of patients at risk for IGM and in need of further
diabetic screening. Emergency physicians should advise patients with elevated RPG
to consider screening for diabetes. For ED screening to be successful, patient
education and collaboration with FPs are essential.
PMID- 24353244
TI - Neurotrophic natural products: chemistry and biology.
AB - Neurodegenerative diseases and spinal cord injury affect approximately 50 million
people worldwide, bringing the total healthcare cost to over 600 billion dollars
per year. Nervous system growth factors, that is, neurotrophins, are a potential
solution to these disorders, since they could promote nerve regeneration. An
average of 500 publications per year attests to the significance of neurotrophins
in biomedical sciences and underlines their potential for therapeutic
applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins
severely restricts their clinical use. On the other hand, small molecules that
modulate neurotrophic activity offer a promising therapeutic approach against
neurological disorders. Nature has provided an impressive array of natural
products that have potent neurotrophic activities. This Review highlights the
current synthetic strategies toward these compounds and summarizes their ability
to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic
natural products could be used not only as starting points in drug design but
also as tools to study the next frontier in biomedical sciences: the brain
activity map project.
PMID- 24353255
TI - Can we reduce costs and prevent more unintended pregnancies? A cost of illness
and cost-effectiveness study comparing two methods of EHC.
AB - OBJECTIVES: To calculate the cost of an unintended pregnancy in 2011 and use this
cost in a cost-effectiveness model comparing ulipristal acetate (UPA) with
levonorgestrel (LNG) for emergency hormonal contraception (EHC). DESIGN:
Retrospective analysis of published data sources and published cost-effectiveness
model. SETTING: Women presenting in primary care in England for EHC within 24 or
72 h of unprotected sexual intercourse (UPSI). INTERVENTIONS: EHC of either LNG
(1.5 mg) or UPA (30 mg). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary
outcome measure is the number and direct and indirect costs of an unintended
pregnancy. The secondary outcome measure is the consequence of unintended
pregnancy: miscarriage, abortion, ectopic pregnancy, stillbirth or live birth.
RESULTS: From the comparative clinical studies of EHC we observe that if 125
women receive either LNG or UPA within 72 h of UPSI, there will be one less
pregnancy due to method failure in the UPA group than in the LNG group. We
calculate the cost of an unintended pregnancy to be L1663 in direct healthcare
costs rising to L2922 with the inclusion of social costs. Using these costs in
the comparative cost-effectiveness model shows that it costs L194 less in direct
health costs alone to prevent one more pregnancy with UPA than with LNG. The
inclusion of social costs of pregnancy increases this cost-saving potential to
L1453 for each extra pregnancy avoided with UPA compared with LNG. CONCLUSIONS:
Clinical trials have demonstrated the superior efficacy of UPA compared with LNG
as a method of EHC. Given that it costs less overall in health and social costs
of pregnancy while preventing more pregnancies, UPA is said to be the dominant
treatment, and primary care services should shift to offering UPA as the
preferred oral option to women presenting within 24 and 72 h of UPSI.
PMID- 24353256
TI - Poor adherence of randomised trials in surgery to CONSORT guidelines for non
pharmacological treatments (NPT): a cross-sectional study.
AB - OBJECTIVE: To systematically assess adherence of randomised trials in surgery to
Consolidated Standards of Reporting Trials (CONSORT) guidelines for non
pharmacological treatments (NPT). Surgical trials are considered more difficult
to design and execute than pharmacological trials. Furthermore, the original
CONSORT statement does not address some aspects that are vital to the transparent
reporting of surgical trials. The CONSORT-NPT extension was designed to address
these issues but adherence in medical and surgical journals has not been
assessed. DESIGN: Cross-sectional study. SAMPLE: We identified eight general
medical and eight surgical journals, indexed in PubMed and published in 2011,
with the highest impact factors in their respective categories. MAIN OUTCOMES:
Adherence to CONSORT statement and CONSORT-NPT extension items. RESULTS: We
identified 54 surgical trials (22 published in medical journals and 32 in
surgical journals). There were eight items for which there was less than 30%
overall compliance (seven were specific to the CONSORT-NPT extension). These
seven items are related to: a full description of the care providers, centres and
blinding status in the abstract (n=7/54, 13%), eligibility criteria for centres
performing the interventions (n=13/54, 24%), how adherence of care providers with
the protocol was assessed or enhanced (n=7/54, 13%), how clustering by care
providers or centres was addressed as it relates to sample size (n=3/54, 6%), how
care providers were allocated to each group (n=9/54, 17%), how clustering by care
providers or centres was addressed as it relates to statistical methods (n=2/54,
4%), a description of care providers (case volume, qualification, expertise, etc)
and centres (volume) in each group (n=0/54, 0%). CONCLUSIONS: Adherence of
surgical trials to CONSORT-NPT extension items is much poorer than to the
standard CONSORT statement. Adherence also appears to be superior in general
medical journals compared with surgical journals. Raising awareness and
conducting qualitative research to identify areas for specific intervention will
be important going forward.
PMID- 24353259
TI - Comment on "synthesis, characterization, and structures of a persistent aniline
radical cation": a new interpretation is necessary.
AB - Further scrutiny for the aniline radical cation: The author of this
Correspondence claims that the original spectrometric data for 2,4,6-tri-tert
butylaniline (TBA) reported in 2012 do not correspond to a stoichiometrically
pure TBA(.+) SbF6 (-) salt, the quantum-chemical data do not support the reported
structural data, and the interpretation of the apparent temperature-dependent
structural changes in the solid state is open to interpretations other than the
Jahn-Teller effect.
PMID- 24353258
TI - Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in
asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre
observational study with blinded investigations.
AB - INTRODUCTION: Aortic stenosis (AS) is the commonest valve disorder in the
developed world requiring surgery. Surgery in patients with severe asymptomatic
AS remains controversial. Exercise testing can identify asymptomatic patients at
increased risk of death and symptom development, but with limited specificity,
especially in older adults. Cardiac MRI (CMR), including myocardial perfusion
reserve (MPR) may be a novel imaging biomarker in AS. AIMS: (1) To improve risk
stratification in asymptomatic patients with AS and (2) to determine whether MPR
is a better predictor of outcome than exercise testing and brain natriuretic
peptide (BNP). METHOD/DESIGN: Multicentre, prospective observational study in the
UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for
predicting outcome. POPULATION: 170 asymptomatic patients with moderate-to-severe
AS, who would be considered for aortic valve replacement (AVR). PRIMARY OUTCOME:
Composite of: typical symptoms necessitating referral for AVR and major adverse
cardiovascular events. FOLLOW-UP: 12-30 months (minimum 12 months). PRIMARY
HYPOTHESIS: MPR will be a better predictor of outcome than exercise testing and
BNP. ETHICS/DISSEMINATION: The study has full ethical approval and is actively
recruiting patients. Data collection will be completed in November 2014 and the
study results will be submitted for publication within 6 months of completion.
CLINICALTRIALSGOV IDENTIFIER: NCT01658345.
PMID- 24353257
TI - Maternal mortality in Malawi, 1977-2012.
AB - BACKGROUND: Millennium Development Goal 5 (MDG 5) targets a 75% reduction in
maternal mortality from 1990 to 2015, yet accurate information on trends in
maternal mortality and what drives them is sparse. We aimed to fill this gap for
Malawi, a country in sub-Saharan Africa with high maternal mortality. METHODS: We
reviewed the literature for population-based studies that provide estimates of
the maternal mortality ratio (MMR) in Malawi, and for studies that list and
justify variables potentially associated with trends in MMR. We used all
population-based estimates of MMR representative of the whole of Malawi to
construct a best-fit trend-line for the range of years with available data,
calculated the proportion attributable to HIV and qualitatively analysed trends
and evidence related to other covariates to logically assess likely candidate
drivers of the observed trend in MMR. RESULTS: 14 suitable estimates of MMR were
found, covering the years 1977-2010. The resulting best-fit line predicted MMR in
Malawi to have increased from 317 maternal deaths/100 000 live-births in 1980 to
748 in 1990, before peaking at 971 in 1999, and falling to 846 in 2005 and 484 in
2010. Concurrent deteriorations and improvements in HIV and health system
investment and provisions are the most plausible explanations for the trend.
Female literacy and education, family planning and poverty reduction could play
more of a role if thresholds are passed in the coming years. CONCLUSIONS: The
decrease in MMR in Malawi is encouraging as it appears that recent efforts to
control HIV and improve the health system are bearing fruit. Sustained efforts to
prevent and treat maternal complications are required if Malawi is to attain the
MDG 5 target and save the lives of more of its mothers in years to come.
PMID- 24353260
TI - Diet and diabetes: a cornerstone for therapy.
AB - An appropriate diet represents the cornerstone for diabetes therapy. Diets that
differ in their carbohydrate, lipid and protein content are used but the evidence
of their effects on the long term is missing. Several confounding factors and
compliance to diet render difficult the evaluation of the 'best diet' for
diabetes. On a short run, however, useful indications can be obtained regarding
the effective diets capable to optimize metabolic control in type 2 diabetes.
PMID- 24353261
TI - Postnatal exposure to flutamide affects CDH1 and CTNNB1 gene expression in adult
pig epididymis and prostate and alters metabolism of testosterone.
AB - In both epididymis and prostate the dynamic cross-talk between the cells is
hormonally regulated and, in part, through direct cell-to-cell interactions.
Functionality of the male reproductive organs may be affected by exposure to
specific chemicals, so-called 'reprotoxicants'. In this study we tested whether
early postnatal and prepubertal exposure to anti-androgen flutamide altered the
expression of adherens junction genes encoding E-cadherin (CDH1) and beta-catenin
(CTNNB1) in adult pig epididymis and prostate. In addition, the expression of
mRNAs and proteins for 5alpha-reductase (ST5AR2) and aromatase (CYP19A1) were
examined to show whether flutamide alters metabolism of testosterone. Thus,
flutamide was injected into male piglets between Days 2 and 10 and between Days
90 and 98 postnatally (PD2 and PD90; 50 mg/kg bw), tissues that were obtained on
postnatal Day 270. To assess the expression of the genes and proteins, real-time
RT-PCR and Western blot were performed respectively. Moreover, adherens junction
proteins were localized by immunohistochemistry. In response to flutamide, CDH1
and CTNNB1 expressions were down-regulated along the epididymis, mostly in PD2
group (p < 0.001, p < 0.01). In the prostate, CDH1 mRNA and protein expressions
were significantly down-regulated (p < 0.01), whereas CTNNB1 mRNA was slightly up
regulated in both flutamide-treated groups. CTNNB1 protein level was markedly
elevated in both PD2 (p < 0.001) and PD90 (p < 0.01) groups. In the epididymis,
the expression of ST5AR2 and CYP19A1 was down- and up-regulated, respectively (p
< 0.05), whereas in the prostate evident decrease in CYP19A1 expression (p <
0.001, p < 0.01, p < 0.05) was demonstrated. In both tissues, membranous
immunolocalization of CTNNB1 suggests its involvement in cell-cell adhesion.
Overall, flutamide administration resulted in suppression of androgen action in
the epididymis and prostate leading to deregulation of CDH1 and CTNNB1 gene
expressions which is probably caused by the alterations in the expression of
ST5AR2 and CYP19A1 in both reproductive organs.
PMID- 24353262
TI - Elevated delta OD 450 due to transient abnormal myelopoiesis in a Down syndrome
fetus with hepatosplenomegaly on ultrasound.
AB - Transient abnormal myelopoiesis (TAM) is a relatively common finding in children
with Down syndrome but has also been diagnosed prenatally, most often presenting
with fetal hepatosplenomegaly. We report a case of TAM with hepatosplenomegaly
found on ultrasound and associated with an increased amniotic fluid Delta OD 450
value. TAM is most commonly transient but can be associated with fatality and
therefore should be considered in the differential diagnosis when fetal
hepatosplenomegaly is found on ultrasound. Amniocentesis with chromosomal
analysis and a Delta OD 450 may aid in diagnosing TAM and predicting the severity
of the liver involvement.
PMID- 24353263
TI - MenHibrix: a new combination meningococcal vaccine for infants and toddlers.
AB - OBJECTIVE: To review the immunogenicity and safety of the Haemophilus influenzae
type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine
(Hib-MenCY-TT) for infants and toddlers. DATA SOURCES: Studies conducted in
humans and limited to publication in English were identified through a MEDLINE
(January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix,
and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y
tetanus toxoid conjugate vaccine. Clinical trial registries, Web sites, and
reference citations from publications identified were reviewed for additional
sources. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials were
included to evaluate the safety and immunogenicity of Hib-MenCY-TT.
Epidemiological data and recommendations from the Advisory Committee on
Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: Hib-MenCY-TT is
available for primary vaccination of infants as a 4-dose series at 2, 4, 6, and
12 to 15 months of age. Hib-MenCY-TT has comparable immunogenicity to licensed
Hib vaccines and produces high levels of N meningitidis antibodies against
serogroups C and Y. The most common adverse events were pain and redness at the
injection site, drowsiness, and irritability. CONCLUSIONS: Hib-MenCY-TT has been
demonstrated to be a safe and immunogenic vaccination for prevention of disease
caused by N meningitidis serogroups C and Y and H influenzae type b in healthy
infants and toddlers. Currently, the ACIP recommends the use of Hib-MenCY-TT
specifically in high-risk infants aged 6 weeks to 18 months. Hib-MenCY-TT
provides the first therapeutic option for vaccination of infants as young as 6
weeks of age who are at increased risk for meningococcal disease.
PMID- 24353265
TI - Correction.
PMID- 24353264
TI - Summarizing specific profiles in Illumina sequencing from whole-genome amplified
DNA.
AB - Advances in both high-throughput sequencing and whole-genome amplification (WGA)
protocols have allowed genomes to be sequenced from femtograms of DNA, for
example from individual cells or from precious clinical and archived samples.
Using the highly curated Caenorhabditis elegans genome as a reference, we have
sequenced and identified errors and biases associated with Illumina library
construction, library insert size, different WGA methods and genome features such
as GC bias and simple repeat content. Detailed analysis of the reads from
amplified libraries revealed characteristics suggesting that majority of
amplified fragment ends are identical but inverted versions of each other. Read
coverage in amplified libraries is correlated with both tandem and inverted
repeat content, while GC content only influences sequencing in long-insert
libraries. Nevertheless, single nucleotide polymorphism (SNP) calls and assembly
metrics from reads in amplified libraries show comparable results with
unamplified libraries. To utilize the full potential of WGA to reveal the real
biological interest, this article highlights the importance of recognizing
additional sources of errors from amplified sequence reads and discusses the
potential implications in downstream analyses.
PMID- 24353266
TI - PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis.
AB - Chlamydia trachomatis infection is the most common bacterial sexually transmitted
disease in the United States. Repeated infections with C. trachomatis lead to
serious sequelae, such as infertility. It is unclear why the adaptive immune
system, specifically the CD8(+) T cell response, is unable to protect against
subsequent C. trachomatis infections. In this article, we characterize the
mucosal CD8(+) T cell response to C. trachomatis in the murine genital tract. We
demonstrate that the immunoinhibitory ligand, PD-L1, contributes to the defective
CD8(+) T cell response. Deletion or inhibition of PD-L1 restores the CD8(+) T
cell response and enhances C. trachomatis clearance.
PMID- 24353268
TI - CCR7 is mainly expressed in teleost gills, where it defines an IgD+IgM- B
lymphocyte subset.
AB - Chemokine receptor CCR7, the receptor for both CCL19 and CCL21 chemokines,
regulates the recruitment and clustering of circulating leukocytes to secondary
lymphoid tissues, such as lymph nodes and Peyer's patches. Even though teleost
fish do not have either of these secondary lymphoid structures, we have recently
reported a homolog to CCR7 in rainbow trout (Oncorhynchus mykiss). In the present
work, we have studied the distribution of leukocytes bearing extracellular CCR7
in naive adult tissues by flow cytometry, observing that among the different
leukocyte populations, the highest numbers of cells with membrane (mem)CCR7 were
recorded in the gill (7.5 +/- 2% CCR7(+) cells). In comparison, head kidney,
spleen, thymus, intestine, and peripheral blood possessed <5% CCR7(+) cells. When
CCR7 was studied at early developmental stages, we detected a progressive
increase in gene expression and protein CCR7 levels in the gills throughout
development. Surprisingly, the majority of the CCR7(+) cells in the gills were
not myeloid cells and did not express membrane CD8, IgM, nor IgT, but expressed
IgD on the cell surface. In fact, most IgD(+) cells in the gills expressed CCR7.
Intriguingly, the IgD(+)CCR7(+) population did not coexpress memIgM. Finally,
when trout were bath challenged with viral hemorrhagic septicemia virus, the
number of CCR7(+) cells significantly decreased in the gills while significantly
increased in head kidney. These results provide evidence of the presence of a
novel memIgD(+)memIgM(-) B lymphocyte subset in trout that expresses memCCR7 and
responds to viral infections. Similarities with IgD(+)IgM(-) subsets in mammals
are discussed.
PMID- 24353267
TI - Targeted chromatin profiling reveals novel enhancers in Ig H and Ig L chain Loci.
AB - The assembly and expression of mouse Ag receptor genes are controlled by a
collection of cis-acting regulatory elements, including transcriptional promoters
and enhancers. Although many powerful enhancers have been identified for Ig (Ig)
and TCR (Tcr) loci, it remained unclear whether additional regulatory elements
remain undiscovered. In this study, we use chromatin profiling of pro-B cells to
define 38 epigenetic states in mouse Ag receptor loci, each of which reflects a
distinct regulatory potential. One of these chromatin states corresponds to known
transcriptional enhancers and identifies a new set of candidate elements in all
three Ig loci. Four of the candidates were subjected to functional assays, and
all four exhibit enhancer activity in B but not in T lineage cells. The new
regulatory elements identified by focused chromatin profiling most likely have
important functions in the creation, refinement, and expression of Ig
repertoires.
PMID- 24353269
TI - Unbiased expression mapping identifies a link between the complement and
cholinergic systems in the rat central nervous system.
AB - The complement system is activated in a wide spectrum of CNS diseases and is
suggested to play a role in degenerative phenomena such as elimination of
synaptic terminals. Still, little is known of mechanisms regulating complement
activation in the CNS. Loss of synaptic terminals in the spinal cord after an
experimental nerve injury is increased in the inbred DA strain compared with the
PVG strain and is associated with expression of the upstream complement
components C1q and C3, in the absence of membrane attack complex activation and
neutrophil infiltration. To further dissect pathways regulating complement
expression, we performed genome-wide expression profiling and linkage analysis in
a large F2(DA * PVG) intercross, which identified quantitative trait loci
regulating expression of C1qa, C1qb, C3, and C9. Unlike C1qa, C1qb, and C9, which
all displayed distinct coregulation with different cis-regulated C-type lectins,
C3 was regulated in a coexpression network immediately downstream of
butyrylcholinesterase. Butyrylcholinesterase hydrolyses acetylcholine, which
exerts immunoregulatory effects partly through TNF-alpha pathways. Accordingly,
increased C3, but not C1q, expression was demonstrated in rat and mouse glia
following TNF-alpha stimulation, which was abrogated in a dose-dependent manner
by acetylcholine. These findings demonstrate new pathways regulating CNS
complement expression using unbiased mapping in an experimental in vivo system. A
direct link between cholinergic activity and complement activation is supported
by in vitro experiments. The identification of distinct pathways subjected to
regulation by naturally occurring genetic variability is of relevance for the
understanding of disease mechanisms in neurologic conditions characterized by
neuronal injury and complement activation.
PMID- 24353270
TI - Prevention of type 2 diabetes mellitus: is it feasible?
AB - The increasing global prevalence of type 2 diabetes mellitus (T2DM) requires the
implementation of preventive strategies to halt this trend, tailored to the
specific needs of individual regions. Risk factors for T2DM are among the main
targets for improving health outcomes and curbing the development of diabetes;
excessive weight and obesity are two of the most important risk factors that need
to be addressed. A growing body of evidence suggests that subjects with pre
diabetes who lose body weight and increase physical activity can delay or prevent
the onset of T2DM, and in some cases, blood glucose levels may return to normal.
Several studies have shown that moderate to intensive levels of exercise are
effective in reducing both intra-abdominal and total adiposity among obese
subjects, both improving cardiovascular risk profile and reducing the risk of
T2DM development. These consistent observations have given rise to large-scale
randomized controlled trials that use lifestyle intervention (including
behavioural strategies for the reinforcement of prescribed changes in nutritional
intake, physical activity or both), with or without pharmacological treatment, in
populations at high risk of developing T2DM. In this review, large-scale national
trials that have focused on the prevention of T2DM are critically evaluated.
PMID- 24353271
TI - High-density polymer microarrays: identifying synthetic polymers that control
human embryonic stem cell growth.
AB - The fabrication of high-density polymer microarray is described, allowing the
simultaneous and efficient evaluation of more than 7000 different polymers in a
single-cellular-based screen. These high-density polymer arrays are applied in
the search for synthetic substrates for hESCs culture. Up-scaling of the
identified hit polymers enables long-term cellular cultivation and promoted
successful stem-cell maintenance.
PMID- 24353272
TI - Protective role of Mincle in bacterial pneumonia by regulation of neutrophil
mediated phagocytosis and extracellular trap formation.
AB - BACKGROUND: Nosocomial infections with Klebsiella pneumoniae are a frequent cause
of Gram-negative bacterial sepsis. To understand the functioning of host innate
immune components in this disorder, we examined a previously uninvestigated role
of the C-type lectin receptor Mincle in pneumonic sepsis caused by K. pneumoniae.
METHODS: Disease progression in wild-type and Mincle(-/-) mice undergoing
pulmonary infection with K. pneumoniae was compared. RESULTS: Whereas the wild
type mice infected with a sublethal dose of bacteria could resolve the infection
with bacterial clearance and regulated host response, the Mincle(-/-) mice were
highly susceptible with a progressive increase in bacterial burden, despite their
ability to mount an inflammatory response that turned to an exaggerated
hyperinflammation with the onset of severe pneumonia. This correlated with severe
lung pathology with a massive accumulation of neutrophils in their lungs.
Importantly, Mincle(-/-) neutrophils displayed a defective ability to phagocytize
nonopsonic bacteria and an impaired ability to form extracellular traps (NETs),
an important neutrophil function against invading pathogens, including K.
pneumoniae. CONCLUSION: Our results demonstrate protective role of Mincle in host
defense against K. pneumoniae pneumonia by coordinating bacterial clearance
mechanisms of neutrophils. A novel role for Mincle in the regulation of
neutrophil NET formation may have implications in chronic disease conditions
characterized by deregulated NET formation.
PMID- 24353273
TI - Physical exercise as therapy for type 2 diabetes mellitus.
AB - Many studies have highlighted the importance of physical activity (PA) for
health, and recent evidence now points to the positive improvements associated
with exercise in type 2 diabetes mellitus (T2DM). However, few physicians are
willing to prescribe exercise as a therapy for diabetic patients. In addition,
there is a lack of information on how to implement exercise therapy especially in
long-term exercise regimens. The purpose of this manuscript is to summarize
standards of exercise therapy for patients with T2DM, both in terms of
prescribing and monitoring, according to the American College of Sports Medicine
and the American Diabetes Association guidelines. We present details of the
exercise therapies used in long-term studies, describing how the parameters for
exercise prescription were applied in clinical practice. These parameters are
described in terms of frequency, intensity, duration, mode and rate of
progression in long-term therapeutic prescriptions. Individual responses to
exercise dose are discussed, and critical issues to be considered in patients
with underlying disease and in T2DM patients are highlighted.
PMID- 24353274
TI - Access to services, quality of care, and family impact for children with autism,
other developmental disabilities, and other mental health conditions.
AB - This cross-sectional study examined perceived access to services, quality of
care, and family impact reported by caregivers of children aged 3-17 years with
autism spectrum disorders, as compared to caregivers of children with other
developmental disabilities and other mental health conditions. The 2009-2010
National Survey of Children with Special Health Care Needs was utilized to
examine the association between child's special needs condition and three
outcomes (N = 18,136): access to services (difficulty using services, difficulty
getting referrals, lack of source of care, and inadequate insurance coverage),
quality of care (lack of care coordination, lack of shared decision making, and
no routine screening), and family impact (financial, employment, and time-related
burden). Multivariate logistic regressions were performed to compare caregivers
of children with autism spectrum disorders to caregivers of children with
developmental disabilities (cerebral palsy, Down syndrome, developmental delay,
or intellectual disability), mental health conditions (attention deficit
hyperactivity disorder, anxiety, behavioral/conduct problems, or depression), or
both developmental disabilities and mental health conditions. Caregivers of
children with autism spectrum disorders were significantly more likely to report
difficulty using services, lack of source of care, inadequate insurance coverage,
lack of shared decision making and care coordination, and adverse family impact
as compared to caregivers of children with developmental disabilities, mental
health conditions, or both.
PMID- 24353275
TI - Is early joint attention associated with school-age pragmatic language?
AB - In order to evaluate evidence for the social-cognitive theory of joint attention,
we examined relations between initiation of and response to joint attention at 12
and 18 months of age and pragmatic and structural language approximately 6 years
later among children with and without autism spectrum disorder. Initiation of
joint attention at 18 months was associated with structural, but not pragmatic,
language for children with and without autism spectrum disorder. School-age
children with autism exhibited difficulties with structural and pragmatic
language relative to non-autistic siblings of children with autism and low-risk
controls. No evidence of the broader autism phenotype was observed. These
findings do not support the social-cognitive theory of joint attention.
PMID- 24353276
TI - Higher coffee intake in pregnancy linked to prolonged gestation, and higher
caffeine intake linked with babies being small for gestational age.
PMID- 24353277
TI - Review: Exercise interventions improve pain and function in people with knee
osteoarthritis compared with no exercise.
PMID- 24353278
TI - A model to develop compassionate relationship-centred care between older people,
relatives and staff identifies seven factors necessary to promote appreciative
caring conversations.
PMID- 24353280
TI - Prognostic models for stable coronary artery disease based on electronic health
record cohort of 102 023 patients.
AB - AIMS: The population with stable coronary artery disease (SCAD) is growing but
validated models to guide their clinical management are lacking. We developed and
validated prognostic models for all-cause mortality and non-fatal myocardial
infarction (MI) or coronary death in SCAD. METHODS AND RESULTS: Models were
developed in a linked electronic health records cohort of 102 023 SCAD patients
from the CALIBER programme, with mean follow-up of 4.4 (SD 2.8) years during
which 20 817 deaths and 8856 coronary outcomes were observed. The Kaplan-Meier 5
year risk was 20.6% (95% CI, 20.3, 20.9) for mortality and 9.7% (95% CI, 9.4,
9.9) for non-fatal MI or coronary death. The predictors in the models were age,
sex, CAD diagnosis, deprivation, smoking, hypertension, diabetes, lipids, heart
failure, peripheral arterial disease, atrial fibrillation, stroke, chronic kidney
disease, chronic pulmonary disease, liver disease, cancer, depression, anxiety,
heart rate, creatinine, white cell count, and haemoglobin. The models had good
calibration and discrimination in internal (external) validation with C-index
0.811 (0.735) for all-cause mortality and 0.778 (0.718) for non-fatal MI or
coronary death. Using these models to identify patients at high risk (defined by
guidelines as 3% annual mortality) and support a management decision associated
with hazard ratio 0.8 could save an additional 13-16 life years or 15-18 coronary
event-free years per 1000 patients screened, compared with models with just age,
sex, and deprivation. CONCLUSION: These validated prognostic models could be used
in clinical practice to support risk stratification as recommended in clinical
guidelines.
PMID- 24353281
TI - Corevalve prosthesis causes anterior mitral leaflet perforation resulting in
severe mitral regurgitation and subsequent endocarditis.
PMID- 24353279
TI - FoxO4 interacts with the sterol regulatory factor SREBP2 and the hypoxia
inducible factor HIF2alpha at the CYP51 promoter.
AB - The late steps of cholesterol biosynthesis are oxygen demanding, requiring eleven
oxygen molecules per synthesized cholesterol molecule. A key enzymatic reaction,
which occurs at the top of the Bloch and Kandutsch-Russell pathways, is the
demethylation of lanosterol and dihydrolanosterol (DHL). This reaction is
catalyzed by lanosterol 14alpha demethylase (CYP51) and requires three oxygen
molecules. Thus, it is the first step in the distal pathway to be susceptible to
oxygen deprivation. Having previously identified that the forkhead transcription
factor 4 (FoxO4) represses CYP51 expression, we aimed to characterize its role at
the CYP51 promoter. Hypoxia-treated 3T3L1 cells showed decreased cholesterol
biosynthesis, accumulation of lanosterol/DHL, and stimulation of FoxO4 expression
and its cytoplasmic translocation to the nucleus. Transfection assays with a
CYP51 promoter reporter gene revealed that FoxO4 and sterol regulatory element
binding protein (SREBP)2 exert a stimulatory effect, whereas FoxO4 and the
hypoxia inducible factor (HIF)2alpha repress CYP51 promoter activity.
Electromobility shift, chromatin immunoprecipitation, pull-down, and
coimmunoprecipitation assays show that FoxO4 interacts with SREBP2 and HIF2alpha
to modulate CYP51 promoter activity. We also show an inverse correlation between
FoxO4 and CYP51 in adipose tissue of ob/ob mice and mouse fetal cortical neurons
exposed to hypoxia. Overall, these studies demonstrate a role for FoxO4 in the
regulation of CYP51 expression.
PMID- 24353282
TI - Initiation of warfarin in patients with atrial fibrillation: early effects on
ischaemic strokes.
AB - AIMS: An increased risk of stroke was observed in two atrial fibrillation (AF)
trials of oral factor Xa inhibitors, when patients were transitioned to open
label warfarin at the end of the study. The objective of this study is to
determine whether initiation of warfarin is associated with an increased risk of
stroke in patients with AF. METHODS AND RESULTS: Using the UK Clinical Practice
Research Datalink, a nested case-control analysis was conducted within a cohort
of 70 766 patients with AF between 1993 and 2008. Stroke cases were randomly
matched with up to 10 controls on age, sex, date of AF diagnosis, and time since
AF diagnosis. Conditional logistic regression was used to estimate adjusted rate
ratios (RRs) with 95% confidence intervals (CIs) of stroke associated with
current warfarin use classified according to time since initiation of treatment
(<30 days, 31-90 days, and >90 days), when compared with non-use. A total of 5519
patients experienced a stroke during follow-up. Warfarin was associated with a
71% increased risk of stroke in the first 30 days of use (RR: 1.71, 95% CI: 1.39
2.12), while decreased risks were observed with initiation >30 days before the
event (31-90 days: RR: 0.50, 95% CI: 0.34-0.75 and >90 days: RR: 0.55, 95% CI:
0.50-0.61, respectively). CONCLUSION: Patients initiating warfarin may be at an
increased risk of stroke during the first 30 days of treatment, supporting the
biological plausibility of a transient hypercoagulable state at the start of the
treatment, although additional studies are needed to confirm these findings.
PMID- 24353283
TI - Different expression of TSH receptor and NIS genes in thyroid cancer: role of
epigenetics.
AB - The TSH receptor (TSHR) and sodium/iodide symporter (NIS) are key players in
radioiodine-based treatment of differentiated thyroid cancers. While NIS (SLC5AS)
expression is diminished/lost in most thyroid tumors, TSHR is usually preserved.
To examine the mechanisms that regulate the expression of NIS and TSHR genes in
thyroid tumor cells, we analyzed their expression after inhibition of ras-BRAF
MAPK and PI3K-Akt-mTOR pathways and the epigenetic control occurring at the gene
promoter level in four human thyroid cancer cell lines. Quantitative real-time
PCR was used to measure NIS and TSHR mRNA in thyroid cancer cell lines (TPC-1,
BCPAP, WRO, and FTC-133). Western blotting was used to assess the levels of total
and phosphorylated ERK and Akt. Chromatin immunoprecipitation was performed for
investigating histone post-translational modifications of the TSHR and NIS genes.
ERK and Akt inhibitors elicited different responses of the cells in terms of TSHR
and NIS mRNA levels. Akt inhibition increased NIS transcript levels and reduced
those of TSHR in FTC-133 cells but had no significant effects in BCPAP. ERK
inhibition increased the expression of both genes in BCPAP cells but had no
effects in FTC-133. Histone post-translational modifications observed in the
basal state of the four cell lines as well as in BCPAP treated with ERK inhibitor
and FTC-133 treated with Akt inhibitor show cell- and gene-specific differences.
In conclusion, our data indicate that in thyroid cancer cells the expression of
TSHR and NIS genes is differently controlled by multiple mechanisms, including
epigenetic events elicited by major signaling pathways involved in thyroid
tumorigenesis.
PMID- 24353284
TI - LGR4 acts as a link between the peripheral circadian clock and lipid metabolism
in liver.
AB - The circadian clock plays an important role in the liver by regulating the major
aspects of energy metabolism. Currently, it is assumed that the circadian clock
regulates metabolism mostly by regulating the expression of liver enzymes at the
transcriptional level, but the underlying mechanism is not well understood. In
this study, we showed that Lgr4 homozygous mutant (Lgr4(m/m)) mice showed
alteration in the rhythms of the respiratory exchange ratio. We further detected
impaired plasma triglyceride rhythms in Lgr4(m/m) mice. Although no significant
changes in plasma cholesterol rhythms were observed in the Lgr4(m/m) mice, their
cholesterol levels were obviously lower. This phenotype was further confirmed in
the context of ob/ob mice, in which lack of LGR4 dampened circadian rhythms of
triglyceride. We next demonstrated that Lgr4 expression exhibited circadian
rhythms in the liver tissue and primary hepatocytes in mice, but we did not
detect changes in the expression levels or circadian rhythms of classic clock
genes, such as Clock, Bmal1 (Arntl), Pers, Rev-erbs, and Crys, in Lgr4(m/m) mice
compared with their littermates. Among the genes related to the lipid metabolism,
we found that the diurnal expression pattern of the Mttp gene, which plays an
important role in the regulation of plasma lipid levels, was impaired in
Lgr4(m/m) mice and primary Lgr4(m/m) hepatocytes. Taken together, our results
demonstrate that LGR4 plays an important role in the regulation of plasma lipid
rhythms, partially through regulating the expression of microsomal triglyceride
transfer protein. These data provide a possible link between the peripheral
circadian clock and lipid metabolism.
PMID- 24353285
TI - Molecular evolution of GPCRs: Ghrelin/ghrelin receptors.
AB - After the discovery in 1996 of the GH secretagogue-receptor type-1a (GHS-R1a) as
an orphan G-protein coupled receptor, many research groups attempted to identify
the endogenous ligand. Finally, Kojima and colleagues successfully isolated the
peptide ligand from rat stomach extracts, determined its structure, and named it
ghrelin. The GHS-R1a is now accepted to be the ghrelin receptor. The existence of
the ghrelin system has been demonstrated in many animal classes through
biochemical and molecular biological strategies as well as through genome
projects. Our work, focused on identifying the ghrelin receptor and its ligand
ghrelin in laboratory animals, particularly nonmammalian vertebrates, has
provided new insights into the molecular evolution of the ghrelin receptor. In
mammals, it is assumed that the ghrelin receptor evolution is in line with the
plate tectonics theory. In contrast, the evolution of the ghrelin receptor in
nonmammalian vertebrates differs from that of mammals: multiplicity of the
ghrelin receptor isoforms is observed in nonmammalian vertebrates only. This
multiplicity is due to genome duplication and polyploidization events that
particularly occurred in Teleostei. Furthermore, it is likely that the evolution
of the ghrelin receptor is distinct from that of its ligand, ghrelin, because
only one ghrelin isoform has been detected in all species examined so far. In
this review, we summarize current knowledge related to the molecular evolution of
the ghrelin receptor in mammalian and nonmammalian vertebrates.
PMID- 24353289
TI - Presence of viral DNA in whole-genome sequencing of brain tumor tissues from the
cancer genome atlas.
PMID- 24353291
TI - Short- and long-term memories formed upon backward conditioning in honeybees
(Apis mellifera).
AB - In classical conditioning, the temporal sequence of stimulus presentations is
critical for the association between the conditioned stimulus (CS) and the
unconditioned stimulus (US). In forward conditioning, the CS precedes the US and
is learned as a predictor for the US. Thus it acquires properties to elicit a
behavioral response, defined as excitatory properties. In backward conditioning,
the US precedes the CS. The CS might be learned as a predictor for the cessation
of the US acquiring inhibitory properties that inhibit a behavioral response.
Interestingly, behavior after backward conditioning is controlled by both
excitatory and inhibitory properties of the CS, but the underlying mechanisms
determining which of these opposing properties control behavior upon retrieval is
poorly understood. We performed conditioning experiments in the honeybee (Apis
mellifera) to investigate the CS properties that control behavior at different
time points after backward conditioning. The CS properties, as characterized by
the retardation or enhancement of subsequent acquisition, were examined 30 min
and 24 h after backward conditioning. We found that 30 min after backward
conditioning, the CS acquired an inhibitory property during backward conditioning
depending on the intertrial interval, the number of trials, and the odor used as
the CS. One day after backward conditioning, we observed significant retardation
of acquisition. In addition, we demonstrated an enhanced, generalized odor
response in the backward conditioned group compared to untreated animals. These
results indicate that two long-lasting opposing memories have been formed in
parallel: one about the excitatory properties of the CS and one about the
inhibitory properties of the CS.
PMID- 24353292
TI - Memory destabilization is critical for the success of the reactivation-extinction
procedure.
AB - It has been suggested that, unlike pure extinction which typically results in the
return of the fear response under a variety of circumstances, memory reactivation
followed by extinction can attenuate the reemergence of conditioned fear. The
reactivation-extinction procedure has attracted the attention of basic and
clinical researchers due to its potential clinical value for the treatment of
psychiatric conditions, such as anxiety and drug abuse disorders. However, mixed
results have been achieved so far in replicating and understanding this paradigm.
It has been proposed that memory destabilization could be critical in this sense.
Using contextual fear conditioning in rats and midazolam as an amnesic agent, we
first determined what reactivation conditions are necessary to destabilize the
mnemonic trace. After establishing the conditions for memory destabilization, a
series of experiments was conducted to determine if destabilization is critical
for the success of the reactivation-extinction procedure. Data confirmed the
importance of memory destabilization prior to extinction inside the
reconsolidation window to attenuate spontaneous recovery and retard reacquisition
of conditioned fear. The present report offers a candidate explanation of the
discrepancy in results obtained with the reactivation-extinction procedure by
different laboratories.
PMID- 24353293
TI - Taylor on presumed consent.
PMID- 24353294
TI - On not taking men as they are: reflections on moral bioenhancement.
PMID- 24353295
TI - Autonomy in the medico-legal courtroom: a principle fit for purpose?
AB - This article examines the way that the principle of autonomy is handled in
(mostly English) law. The law pays loud lip-service to autonomy, saying that it
is the governing principle in many areas. This is particularly true for cases
involving bioethics. The courts are rarely philosophically explicit about which
account of autonomy is favoured, but three accounts (Millian self-determination,
Kantian deontology, and relational autonomy-in which the social nexus of the
subject is explicitly recognised) can be identified. Despite the law's
traditional rhetorical insistence that autonomy rules absolutely, that rule is,
in practice, unworkable. Other principles, such as beneficence and dignity, have
to be drafted in to help. Much of the philosophical work that autonomy should do
in the law is delegated to the notion of capacity, but that notion too is
insufficiently examined by the courts, and is problematic.
PMID- 24353296
TI - Motor learning of novel dynamics is not represented in a single global coordinate
system: evaluation of mixed coordinate representations and local learning.
AB - Successful motor performance requires the ability to adapt motor commands to task
dynamics. A central question in movement neuroscience is how these dynamics are
represented. Although it is widely assumed that dynamics (e.g., force fields) are
represented in intrinsic, joint-based coordinates (Shadmehr R, Mussa-Ivaldi FA. J
Neurosci 14: 3208-3224, 1994), recent evidence has questioned this proposal. Here
we reexamine the representation of dynamics in two experiments. By testing
generalization following changes in shoulder, elbow, or wrist configurations, the
first experiment tested for extrinsic, intrinsic, or object-centered
representations. No single coordinate frame accounted for the pattern of
generalization. Rather, generalization patterns were better accounted for by a
mixture of representations or by models that assumed local learning and graded,
decaying generalization. A second experiment, in which we replicated the design
of an influential study that had suggested encoding in intrinsic coordinates
(Shadmehr and Mussa-Ivaldi 1994), yielded similar results. That is, we could not
find evidence that dynamics are represented in a single coordinate system. Taken
together, our experiments suggest that internal models do not employ a single
coordinate system when generalizing and may well be represented as a mixture of
coordinate systems, as a single system with local learning, or both.
PMID- 24353297
TI - The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and
molecular effects on central neurons.
AB - Neuropeptides have widespread effects on behavior, but how these molecules alter
the activity of their target cells is poorly understood. We employed a new model
system in Drosophila melanogaster to assess the electrophysiological and
molecular effects of neuropeptides, recording in situ from larval motor neurons,
which transgenically express a receptor of choice. We focused on two
neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF),
which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment
depolarized motor neurons expressing the PDF receptor (PDFR), increasing
excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons
expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically
encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP
(cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a
small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi
interference to disrupt the G-protein Galphao blocked the electrophysiological
responses to sNPF, showing that sNPFR acts via Galphao signaling. Using a
fluorescent sensor for intracellular calcium, we observed that sNPF-induced
hyperpolarization blocked spontaneous waves of activity propagating along the
ventral nerve cord, demonstrating that the electrical effects of sNPF can cause
profound changes in natural network activity in the brain. This new model system
provides a platform for mechanistic analysis of how neuropeptides can affect
target cells at the electrical and molecular level, allowing for predictions of
how they regulate brain circuits that control behaviors such as sleep and
feeding.
PMID- 24353299
TI - Effects of short-latency afferent inhibition on short-interval intracortical
inhibition.
AB - Peripheral nerve stimulation inhibits the motor cortex, and the process has been
termed short-latency afferent inhibition (SAI) at interstimulus intervals (ISIs)
of ~20 ms. The objective of the present study was to test how SAI interacts with
short-interval intracortical inhibition (SICI) under different stimulation
conditions. We studied 20 healthy volunteers. Surface electromyogram was recorded
from the first dorsal interosseous muscle. Using paired- and triple-pulse
paradigms, we investigated how SAI interacts with SICI under these different
conditions. The effects of different conditioning stimulus (CS) intensities (0.6
0.9 active motor threshold), SAI latencies (23 and 25 ms), and ISIs (2 and 3 ms)
for SICI were examined in rest and active conditions. SAI had inhibitory
interactions with SICI at different CS intensities for rest or active SICI, at
SAI latencies of 23 and 25 ms. This interaction occurred at weak CS intensities
for SICI when there was no inhibition, and SICI became facilitatory in the
presence of SAI. This can be explained by SICI inhibiting SAI and not by
saturation of inhibition. The interaction between SAI and SICI was greater for
SICI at ISI of 3 ms than for ISI of 2 ms, suggesting that different circuits may
be activated at these ISIs. We conclude that SAI and SICI have inhibitory
interactions that are influenced by factors such as ISI and muscle activities,
which should be considered in design and interpretation of cortical interaction
studies.
PMID- 24353298
TI - Effects of muscimol inactivations of functional domains in motor, premotor, and
posterior parietal cortex on complex movements evoked by electrical stimulation.
AB - Parietal and frontal cortex are central to controlling forelimb movements. We
previously showed that movements such as reach, grasp, and defense can be evoked
from primary motor (M1), premotor (PMC), and posterior parietal (PPC) cortex when
500-ms trains of electrical pulses are delivered via microelectrodes. Stimulation
sites that evoked a specific movement clustered into domains, which shared a
topographic pattern in New World monkeys and prosimian galagos. Matched
functional domains in parietal and frontal cortex were preferentially
interconnected. We reasoned that matched functional domains form parallel
networks involved in specific movements. To test the roles of domains in M1, PMC,
and PPC, we systematically inactivated with muscimol domains in one region and
determined if functional changes occurred in matching domains in other regions.
The most common changes were higher current thresholds for stimulation-evoked
movements and shorter, not fully developed, trajectories of movements.
Inactivations of an M1 functional domain greatly reduced or abolished movements
evoked from the matching domains in PMC or PPC, whereas movements evoked from
nonmatching domains remained mostly unaffected. In contrast, inactivating PMC or
PPC domains did not consistently abolish the ability to evoke movements from
matching M1 domains. However, inactivation of PMC domains suppressed or altered
the movements evoked from PPC domains. Thus movement sequences evoked from PMC
depend on M1 and movement sequences evoked from PPC depend on both M1 and PMC.
Overall, the results support the conclusion that PPC, PMC, and M1 are subdivided
into functional domains that are hierarchically related within parallel networks.
PMID- 24353300
TI - Large-scale, high-density (up to 512 channels) recording of local circuits in
behaving animals.
AB - Monitoring representative fractions of neurons from multiple brain circuits in
behaving animals is necessary for understanding neuronal computation. Here, we
describe a system that allows high-channel-count recordings from a small volume
of neuronal tissue using a lightweight signal multiplexing headstage that permits
free behavior of small rodents. The system integrates multishank, high-density
recording silicon probes, ultraflexible interconnects, and a miniaturized
microdrive. These improvements allowed for simultaneous recordings of local field
potentials and unit activity from hundreds of sites without confining free
movements of the animal. The advantages of large-scale recordings are illustrated
by determining the electroanatomic boundaries of layers and regions in the
hippocampus and neocortex and constructing a circuit diagram of functional
connections among neurons in real anatomic space. These methods will allow the
investigation of circuit operations and behavior-dependent interregional
interactions for testing hypotheses of neural networks and brain function.
PMID- 24353301
TI - Central auditory neurons display flexible feature recombination functions.
AB - Recognition of natural stimuli requires a combination of selectivity and
invariance. Classical neurobiological models achieve selectivity and invariance,
respectively, by assigning to each cortical neuron either a computation
equivalent to the logical "AND" or a computation equivalent to the logical "OR."
One powerful OR-like operation is the MAX function, which computes the maximum
over input activities. The MAX function is frequently employed in computer vision
to achieve invariance and considered a key operation in visual cortex. Here we
explore the computations for selectivity and invariance in the auditory system of
a songbird, using natural stimuli. We ask two related questions: does the MAX
operation exist in auditory system? Is it implemented by specialized "MAX"
neurons, as assumed in vision? By analyzing responses of individual neurons to
combinations of stimuli we systematically sample the space of implemented feature
recombination functions. Although we frequently observe the MAX function, we show
that the same neurons that implement it also readily implement other operations,
including the AND-like response. We then show that sensory adaptation, a
ubiquitous property of neural circuits, causes transitions between these
operations in individual neurons, violating the fixed neuron-to-computation
mapping posited in the state-of-the-art object-recognition models. These
transitions, however, accord with predictions of neural-circuit models
incorporating divisive normalization and variable polynomial nonlinearities at
the spike threshold. Because these biophysical properties are not tied to a
particular sensory modality but are generic, the flexible neuron-to-computation
mapping demonstrated in this study in the auditory system is likely a general
property.
PMID- 24353303
TI - Electrical noise modulates perception of electrical pulses in humans: sensation
enhancement via stochastic resonance.
AB - Although noise is usually considered to be harmful for signal detection and
information transmission, stochastic resonance (SR) describes the
counterintuitive phenomenon of noise enhancing the detection and transmission of
weak input signals. In mammalian sensory systems, SR-related phenomena may arise
both in the peripheral and the central nervous system. Here, we investigate
behavioral SR effects of subliminal electrical noise stimulation on the
perception of somatosensory stimuli in humans. We compare the likelihood to
detect near-threshold pulses of different intensities applied on the left index
finger during presence vs. absence of subliminal noise on the same or an adjacent
finger. We show that (low-pass) noise can enhance signal detection when applied
on the same finger. This enhancement is strong for near-threshold pulses below
the 50% detection threshold and becomes stronger when near-threshold pulses are
applied as brief trains. The effect reverses at pulse intensities above
threshold, especially when noise is replaced by subliminal sinusoidal
stimulation, arguing for a peripheral direct current addition. Unfiltered noise
applied on longer pulses enhances detection of all pulse intensities. Noise
applied to an adjacent finger has two opposing effects: an inhibiting effect
(presumably due to lateral inhibition) and an enhancing effect (most likely due
to SR in the central nervous system). In summary, we demonstrate that subliminal
noise can significantly modulate detection performance of near-threshold stimuli.
Our results indicate SR effects in the peripheral and central nervous system.
PMID- 24353302
TI - Thalamic olfaction: characterizing odor processing in the mediodorsal thalamus of
the rat.
AB - Thalamus is a key crossroad structure involved in various functions relative to
visual, auditory, gustatory, and somatosensory senses. Because of the specific
organization of the olfactory pathway (i.e., no direct thalamic relay between
sensory neurons and primary cortex), relatively little attention has been
directed toward the thalamus in olfaction. However, an olfactory thalamus exists:
the mediodorsal nucleus of the thalamus (MDT) receives input from various
olfactory structures including the piriform cortex. How the MDT contributes to
olfactory perception remains unanswered. The present study is a first step to
gain insight into the function of the MDT in olfactory processing. Spontaneous
and odor-evoked activities were recorded in both the MDT (single unit and local
field potential) and the piriform cortex (local field potential) of urethane
anesthetized rats. We demonstrate that: 1) odorant presentation induces a
conjoint, coherent emergence of beta-frequency-band oscillations in both the MDT
and the piriform cortex; 2) 51% of MDT single units were odor-responsive with
narrow-tuning characteristics across an odorant set, which included biological,
monomolecular, and mixture stimuli. In fact, a majority of MDT units responded to
only one odor within the set; 3) the MDT and the piriform cortex showed tightly
related activities with, for example, nearly 20% of MDT firing in phase with
piriform cortical beta-frequency oscillations; and 4) MDT-piriform cortex
coherence was state-dependent with enhanced coupling during slow-wave activity.
These data are discussed in the context of the hypothesized role of MDT in
olfactory perception and attention.
PMID- 24353304
TI - Activity in early visual areas predicts interindividual differences in binocular
rivalry dynamics.
AB - When dissimilar images are presented to the two eyes, binocular rivalry (BR)
occurs, and perception alternates spontaneously between the images. Although
neural correlates of the oscillating perception during BR have been found in
multiple sites along the visual pathway, the source of BR dynamics is unclear.
Psychophysical and modeling studies suggest that both low- and high-level
cortical processes underlie BR dynamics. Previous neuroimaging studies have
demonstrated the involvement of high-level regions by showing that frontal and
parietal cortices responded time locked to spontaneous perceptual alternation in
BR. However, a potential contribution of early visual areas to BR dynamics has
been overlooked, because these areas also responded to the physical stimulus
alternation mimicking BR. In the present study, instead of focusing on activity
during perceptual switches, we highlighted brain activity during suppression
periods to investigate a potential link between activity in human early visual
areas and BR dynamics. We used a strong interocular suppression paradigm called
continuous flash suppression to suppress and fluctuate the visibility of a probe
stimulus and measured retinotopic responses to the onset of the invisible probe
using functional MRI. There were ~130-fold differences in the median suppression
durations across 12 subjects. The individual differences in suppression durations
could be predicted by the amplitudes of the retinotopic activity in extrastriate
visual areas (V3 and V4v) evoked by the invisible probe. Weaker responses were
associated with longer suppression durations. These results demonstrate that
retinotopic representations in early visual areas play a role in the dynamics of
perceptual alternations during BR.
PMID- 24353305
TI - TRPC3 mediates hyperexcitability and epileptiform activity in immature cortex and
experimental cortical dysplasia.
AB - Neuronal hyperexcitability plays an important role in epileptogenesis. Conditions
of low extracellular calcium (Ca) or magnesium (Mg) can induce hyperexcitability
and epileptiform activity with unclear mechanisms. Transient receptor potential
canonical type 3 (TRPC3) channels play a pivotal role in neuronal excitability
and are activated in low-Ca and/or low-Mg conditions to depolarize neurons. TRPC3
staining was highly enriched in immature, but very weak in mature, control
cortex, whereas it was strong in dysplastic cortex at all ages. Depolarization
and susceptibility to epileptiform activity increased with decreasing Ca and Mg.
Combinations of low Ca and low Mg induced larger depolarization in pyramidal
neurons and greater susceptibility to epileptiform activity in immature and
dysplastic cortex than in mature and control cortex, respectively. Intracellular
application of anti-TRPC3 antibody to block TRPC3 channels and bath application
of the selective TRPC3 inhibitor Pyr3 greatly diminished depolarization in
immature control and both immature and mature dysplastic cortex with strong TRPC3
expression. Epileptiform activity was initiated in low Ca and low Mg when
synaptic activity was blocked, and Pyr3 completely suppressed this activity. In
conclusion, TRPC3 primarily mediates low Ca- and low Mg-induced depolarization
and epileptiform activity, and the enhanced expression of TRPC3 could make
dysplastic and immature cortex more hyperexcitable and more susceptible to
epileptiform activity.
PMID- 24353306
TI - Testosterone and glucose metabolism in men: current concepts and controversies.
AB - A wealth of observational studies show that low testosterone is associated with
insulin resistance and with an increased risk of diabetes and the metabolic
syndrome. Experimental studies have identified potential mechanisms by which low
testosterone may lead to insulin resistance. Visceral adipose tissue is an
important intermediate in this relationship. Actions of testosterone or its
metabolite oestradiol on other tissues such as muscle, liver, bone or the brain,
and body composition-independent effects may also play a role. However,
definitive evidence from randomised controlled trials (RCTs) to clarify whether
the association of low testosterone with disordered glucose metabolism is
causative is currently lacking. It therefore remains possible that this
association is due to reverse causation, or simply originates by association with
common health and lifestyle factors. RCTs of testosterone therapy in men with or
without diabetes consistently show modest metabolically favourable changes in
body composition. Despite this, testosterone effects on glucose metabolism have
been inconsistent. Recent evidence suggests that the hypothalamic-pituitary
testicular axis suppression in the majority of obese men with metabolic disorders
is functional, and may be, at least in part, reversible with weight loss. Until
further evidence is available, lifestyle measures with emphasis on weight
reduction, treatment of comorbidities and optimisation of diabetic control should
remain the first-line treatment in these men. Such measures, if successful, may
be sufficient to normalise testosterone levels in men with metabolic disorders,
who typically have only modest reductions in circulating testosterone levels.
PMID- 24353307
TI - Mechanism of the beneficial and protective effects of exenatide in diabetic rats.
AB - Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the
treatment of diabetes mellitus. This study examines the mechanism of the
protective effects of exenatide in experimental diabetes, employing four groups
of ten rats each, in which two groups were streptozotocin-induced diabetic and
two were control groups. One control and one diabetic group were treated with
exenatide (1 MUg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for
biochemical analyses while pancreatic tissue was taken for immunofluorescence and
immunoelectron microscopy studies and real-time PCR to examine the expression of
genes. The results show that exenatide improved BW gain and reduced blood glucose
in diabetic rats compared with controls. Similarly, exenatide enhanced insulin
release from the pancreatic fragments and improved liver and kidney functions and
lipid profile in diabetic rats compared with controls. Exenatide not only induced
significant increases in serum insulin level but also elevated the number of
insulin-, GLP1- and exenatide-positive cells compared with untreated controls.
Exenatide also elevated the number of catalase- and glutathione reductase
positive cells in diabetic rat pancreas compared with controls. Exenatide caused
significant elevation in the expressions of pancreatic duodenal homeobox-1, heat
shock protein-70, glutathione peroxidase, insulin receptor and GLP1 receptor
genes in the pancreas of both control and diabetic rats compared with untreated
animals. The results have demonstrated that exenatide can exert its beneficial
and protective effects by elevating the levels of endogenous antioxidants and
genes responsible for the survival, regeneration and proliferation of pancreatic
beta-cell.
PMID- 24353308
TI - Interaction improves perception of gloss.
AB - Rendering materials on displays becomes ubiquitous in industrial design,
architecture, and visualization. Yet the experience of the material from other
modes of perception is missing in that representation. This forces observers to
rely on visual cues only while judging material properties. In the present study,
we compare judgments of rough and glossy surfaces by interacting and passive
observers. We investigate whether observers actively exploring rendered stimuli
judge properties differently than observers passively watching renderings.
Resulting interobserver agreement is significantly higher for interacting
observers.
PMID- 24353309
TI - The role of eye movements in depth from motion parallax during infancy.
AB - Motion parallax is a motion-based, monocular depth cue that uses an object's
relative motion and velocity as a cue to relative depth. In adults, and in
monkeys, a smooth pursuit eye movement signal is used to disambiguate the depth
sign provided by these relative motion cues. The current study investigates
infants' perception of depth from motion parallax and the development of two
oculomotor functions, smooth pursuit and the ocular following response (OFR) eye
movements. Infants 8 to 20 weeks of age were presented with three tasks in a
single session: depth from motion parallax, smooth pursuit tracking, and OFR to
translation. The development of smooth pursuit was significantly related to age,
as was sensitivity to motion parallax. OFR eye movements also corresponded to
both age and smooth pursuit gain, with groups of infants demonstrating asymmetric
function in both types of eye movements. These results suggest that the
development of the eye movement system may play a crucial role in the sensitivity
to depth from motion parallax in infancy. Moreover, describing the development of
these oculomotor functions in relation to depth perception may aid in the
understanding of certain visual dysfunctions.
PMID- 24353310
TI - Collismycin A biosynthesis in Streptomyces sp. CS40 is regulated by iron levels
through two pathway-specific regulators.
AB - Two putative pathway-specific regulators have been identified in the collismycin
A gene cluster: ClmR1, belonging to the TetR-family, and the LuxR-family
transcriptional regulator ClmR2. Inactivation of clmR1 led to a moderate increase
of collismycin A yields along with an early onset of its production, suggesting
an inhibitory role for the product of this gene. Inactivation of clmR2 abolished
collismycin A biosynthesis, whereas overexpression of ClmR2 led to a fourfold
increase in production yields, indicating that ClmR2 is an activator of
collismycin A biosynthesis. Expression analyses of the collismycin gene cluster
in the wild-type strain and in DeltaclmR1 and DeltaclmR2 mutants confirmed the
role proposed for both regulatory genes, revealing that ClmR2 positively controls
the expression of most of the genes in the cluster and ClmR1 negatively regulates
both its own expression and that of clmR2. Additionally, production assays and
further transcription analyses confirmed the existence of a higher regulatory
level modulating collismycin A biosynthesis in response to iron concentrations in
the culture medium. Thus, high iron levels inhibit collismycin A biosynthesis
through the repression of clmR2 transcription. These results have allowed us to
propose a regulatory model that integrates the effect of iron as the main
environmental stimulus controlling collismycin A biosynthesis.
PMID- 24353313
TI - Phosphodiesterase 5 inhibitors enhance chemotherapy killing in
gastrointestinal/genitourinary cancer cells.
AB - The present studies determined whether clinically relevant phosphodiesterase 5
(PDE5) inhibitors interacted with clinically relevant chemotherapies to kill
gastrointestinal/genitourinary cancer cells. In bladder cancer cells, regardless
of H-RAS mutational status, at clinically achievable doses, PDE5 inhibitors
interacted in a greater than additive fashion with doxorubicin/mitomycin
C/gemcitabine/cisplatin/paclitaxel to cause cell death. In pancreatic tumor cells
expressing mutant active K-RAS, PDE5 inhibitors interacted in a greater than
additive fashion with doxorubicin/gemcitabine/paclitaxel to cause cell death. The
most potent PDE5 inhibitor was sildenafil. Knock down of PDE5 expression
recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy
drugs. Expression of cellular FLICE-like inhibitory protein-short did not
significantly inhibit chemotherapy lethality but did significantly reduce
enhanced killing in combination with sildenafil. Overexpression of B-cell
lymphoma-extra large suppressed individual and combination drug toxicities. Knock
down of CD95 or Fas-associated death domain protein suppressed drug combination
toxicity. Combination toxicity was also abolished by necrostatin or receptor
interacting protein 1 knock down. Treatment with PDE5 inhibitors and chemotherapy
drugs promoted autophagy, which was maximal at ~24 hour posttreatment, and 3
methyl adenine or knock down of Beclin1 suppressed drug combination lethality by
~50%. PDE5 inhibitors enhanced and prolonged the induction of DNA damage as
judged by Comet assays and gammahistone 2AX (gammaH2AX) and checkpoint kinase 2
(CHK2) phosphorylation. Knock down of ataxia telangiectasia mutated suppressed
gammaH2AX and CHK2 phosphorylation and enhanced drug combination lethality.
Collectively our data demonstrate that the combination of PDE5 inhibitors with
standard of care chemotherapy agents for gastrointestinal/genitourinary cancers
represents a novel modality.
PMID- 24353314
TI - NKAP is a novel RS-related protein that interacts with RNA and RNA binding
proteins.
AB - NKAP is a highly conserved protein with roles in transcriptional repression, T
cell development, maturation and acquisition of functional competency and
maintenance and survival of adult hematopoietic stem cells. Here we report the
novel role of NKAP in splicing. With NKAP-specific antibodies we found that NKAP
localizes to nuclear speckles. NKAP has an RS motif at the N-terminus followed by
a highly basic domain and a DUF 926 domain at the C-terminal region. Deletion
analysis showed that the basic domain is important for speckle localization. In
pull-down experiments, we identified RNA-binding proteins, RNA helicases and
splicing factors as interaction partners of NKAP, among them FUS/TLS. The FUS/TLS
NKAP interaction takes place through the RS domain of NKAP and the RGG1 and RGG3
domains of FUS/TLS. We analyzed the ability of NKAP to interact with RNA using in
vitro splicing assays and found that NKAP bound both spliced messenger RNA (mRNA)
and unspliced pre-mRNA. Genome-wide analysis using crosslinking and
immunoprecipitation-seq revealed NKAP association with U1, U4 and U5 small
nuclear RNA, and we also demonstrated that knockdown of NKAP led to an increase
in pre-mRNA percentage. Our results reveal NKAP as nuclear speckle protein with
roles in RNA splicing and processing.
PMID- 24353315
TI - Promoter occupancy of the basal class I transcription factor A differs strongly
between active and silent VSG expression sites in Trypanosoma brucei.
AB - Monoallelic expression within a gene family is found in pathogens exhibiting
antigenic variation and in mammalian olfactory neurons. Trypanosoma brucei, a
lethal parasite living in the human bloodstream, expresses variant surface
glycoprotein (VSG) from 1 of 15 bloodstream expression sites (BESs) by virtue of
a multifunctional RNA polymerase I. The active BES is transcribed in an
extranucleolar compartment termed the expression site body (ESB), whereas silent
BESs, located elsewhere within the nucleus, are repressed epigenetically. The
regulatory mechanisms, however, are poorly understood. Here we show that two
essential subunits of the basal class I transcription factor A (CITFA)
predominantly occupied the promoter of the active BES relative to that of a
silent BES, a phenotype that was maintained after switching BESs in situ. In
these experiments, high promoter occupancy of CITFA was coupled to high levels of
both promoter-proximal RNA abundance and RNA polymerase I occupancy. Accordingly,
fluorescently tagged CITFA-7 was concentrated in the nucleolus and the ESB.
Because a ChIP-seq analysis found that along the entire BES, CITFA-7 is
specifically enriched only at the promoter, our data strongly indicate that
monoallelic BES transcription is activated by a mechanism that functions at the
level of transcription initiation.
PMID- 24353316
TI - Nucleosomes accelerate transcription factor dissociation.
AB - Transcription factors (TF) bind DNA-target sites within promoters to activate
gene expression. TFs target their DNA-recognition sequences with high specificity
by binding with resident times of up to hours in vitro. However, in vivo TFs can
exchange on the order of seconds. The factors that regulate TF dynamics in vivo
and increase dissociation rates by orders of magnitude are not known. We
investigated TF binding and dissociation dynamics at their recognition sequence
within duplex DNA, single nucleosomes and short nucleosome arrays with single
molecule total internal reflection fluorescence (smTIRF) microscopy. We find that
the rate of TF dissociation from its site within either nucleosomes or nucleosome
arrays is increased by 1000-fold relative to duplex DNA. Our results suggest that
TF binding within chromatin could be responsible for the dramatic increase in TF
exchange in vivo. Furthermore, these studies demonstrate that nucleosomes
regulate DNA-protein interactions not only by preventing DNA-protein binding but
by dramatically increasing the dissociation rate of protein complexes from their
DNA-binding sites.
PMID- 24353317
TI - Transient kinetics measured with force steps discriminate between double-stranded
DNA elongation and melting and define the reaction energetics.
AB - Under a tension of ~65 pN, double-stranded DNA undergoes an overstretching
transition from its basic (B-form) conformation to a 1.7 times longer
conformation whose nature is only recently starting to be understood. Here we
provide a structural and thermodynamic characterization of the transition by
recording the length transient following force steps imposed on the lambda-phage
DNA with different melting degrees and temperatures (10-25 degrees C). The
shortening transient following a 20-35 pN force drop from the overstretching
force shows a sequence of fast shortenings of double-stranded extended (S-form)
segments and pauses owing to reannealing of melted segments. The lengthening
transients following a 2-35 pN stretch to the overstretching force show the
kinetics of a two-state reaction and indicate that the whole 70% extension is a B
S transition that precedes and is independent of melting. The temperature
dependence of the lengthening transient shows that the entropic contribution to
the B-S transition is one-third of the entropy change of thermal melting,
reinforcing the evidence for a double-stranded S-form that maintains a
significant fraction of the interstrand bonds. The cooperativity of the unitary
elongation (22 bp) is independent of temperature, suggesting that structural
factors, such as the nucleic acid sequence, control the transition.
PMID- 24353318
TI - Inferring short tandem repeat variation from paired-end short reads.
AB - The advances of high-throughput sequencing offer an unprecedented opportunity to
study genetic variation. This is challenged by the difficulty of resolving
variant calls in repetitive DNA regions. We present a Bayesian method to estimate
repeat-length variation from paired-end sequence read data. The method makes
variant calls based on deviations in sequence fragment sizes, allowing the
analysis of repeats at lengths of relevance to a range of phenotypes. We
demonstrate the method's ability to detect and quantify changes in repeat lengths
from short read genomic sequence data across genotypes. We use the method to
estimate repeat variation among 12 strains of Arabidopsis thaliana and
demonstrate experimentally that our method compares favourably against existing
methods. Using this method, we have identified all repeats across the genome,
which are likely to be polymorphic. In addition, our predicted polymorphic
repeats also included the only known repeat expansion in A. thaliana, suggesting
an ability to discover potential unstable repeats.
PMID- 24353319
TI - Can aminotransferase-to-platelet ratio index and other non-invasive markers
effectively reduce liver biopsies for renal transplant evaluation of hepatitis C
virus-positive patients?
AB - BACKGROUND: Advanced fibrosis or cirrhosis is still regarded as a
contraindication for kidney transplantation alone by most centers. The value of
aminotransferase to platelet ratio index (APRI) and other non-invasive markers
has been less studied in hepatitis C virus (HCV)-positive patients with
concurrent end-stage renal disease to predict hepatic fibrosis. Can these be used
to effectively decrease the number of biopsies done in these patients being
evaluated for transplantation? METHODS: Our study population included 255
patients with liver biopsy data. All patient information was collected and
reviewed from medical records. The diagnostic accuracy of the predictive models
was analyzed by calculating sensitivity, specificity, positive predictive value
and negative predictive value. RESULTS: The variables associated with F3-F4 were
aspartate aminotransferase (P = 0.007), bilirubin (P <= 0.001), platelet count (P
= 0.01) and APRI (P <= 0.001). The use of any one laboratory abnormality to
predict liver biopsy scores did not show high positive predictive values (22.6
72.7%). Having abnormal liver findings or cirrhosis on imaging was associated
with high specificities (92.0-97.8%) but low sensitivities (31.4-42.9%). Using
APRI levels of >=0.40 and <=0.95 as an indication for liver biopsy, 50% of
patients with F3-F4 would have correctly avoided having a biopsy. However, 33% of
patients with F3-F4 would have been mislabeled and not be indicated for biopsy.
CONCLUSIONS: Our data suggest that there may not currently be a simple and
sufficiently accurate non-invasive test to replace liver biopsy in renal
transplant workup for HCV-positive patients. The risks outweigh the benefits when
it comes to using non-invasive markers like the APRI.
PMID- 24353321
TI - Can peritoneal dialysis be applied for unplanned initiation of chronic dialysis?
AB - Late referral of patients with chronic kidney disease (CKD) and unforeseeable
deterioration of residual renal function in known CKD patients remain a major
problem leading to the need of unplanned start on chronic dialysis without a
mature access for dialysis. In most centres worldwide, these patients are started
on haemodialysis (HD) using a temporary tunnelled central venous catheter (CVC)
for access. However, during the last decade, increasing clinical experience with
unplanned start on peritoneal dialysis (PD) right after PD catheter implantation
has been published. Key studies are reviewed in the present paper, and the
results seem to indicate that compared with patients starting PD in a planned
setting with peritoneal resting after PD catheter implantation, patients starting
unplanned PD have an increased risk of mechanical complications but apparently no
increased risk of infectious complications. In contrast, patients starting
unplanned HD using a temporary CVC have an increased risk of both mechanical and
infectious complications when compared with patients starting planned HD using an
arterio-venous fistula or a permanent CVC. Regarding clinical outcome in terms of
survival, unplanned PD seems to be at least as safe as unplanned HD. Combining
the unplanned PD programme with a nurse-assisted PD programme is crucial in order
to offer the patient a real opportunity to choose a home-based dialysis option.
In conclusion, unplanned start on PD seems to be a feasible, safe and efficient
alternative to unplanned start on HD for the late referred patient with end-stage
renal disease and urgent need for dialysis.
PMID- 24353320
TI - Glycemic load is associated with oxidative stress among prevalent maintenance
hemodialysis patients.
AB - BACKGROUND: High glycemic index (GI) and glycemic load (GL) are associated with
increased levels of oxidative stress and systemic inflammation in the general
population. Maintenance hemodialysis (MHD) patients are known to have excessive
oxidative stress burden and inflammation. In this study, we examined the
relationship between dietary GI or GL and markers of oxidative stress or
inflammation among prevalent MHD patients. METHODS: A registered dietitian
obtained GI, GL and other dietary data from 58 MHD patients. Two separate 24-h
diet recalls (a hemodialysis day and a non-hemodialysis day) were analyzed using
the Nutrition Data System for Research (NDS-R) software. Plasma or serum
concentrations of F2-isoprostanes, high sensitivity C-reactive protein (hsCRP),
leptin and adiponectin (ADPN) were measured in fasting state. Fat mass was
measured by dual-energy X-ray absorptiometry (DEXA). Cross-sectional associations
between GI, GL and markers of interest were examined by multiple regression
analysis with adjustment for potential covariates. RESULTS: Mean (+/-SD) age,
body mass index (BMI) and total trunk fat were 47 +/- 12 years, 29.5 +/- 6.8
kg/m(2) and 16.4 +/- 8.8 kg, respectively. Dietary GI was associated with trunk
fat (r = -0.182, P = 0.05) but not with F2-isoprostanes and hsCRP. In contrast,
GL was significantly associated with F2-isoprostanes (P = 0.002), in unadjusted
analysis, which remained in adjusted analyses, adjusting for age and sex (P =
0.005), and after adjusting for BMI, trunk fat and waist/hip ratio (P = 0.004).
Addition of leptin or ADPN did not alter the significance of the association. GL
also correlated with hsCRP (P = 0.03), but this association was modified by BMI
and trunk fat. CONCLUSIONS: Dietary GL is significantly associated with markers
of oxidative stress and inflammation among prevalent MHD patients, independent of
the body composition and adipocytokines. These data indicate the importance of
the contents of dietary nutrient intake composition and its potential role in
determining the metabolic disturbances in MHD patients.
PMID- 24353322
TI - Bridging the gap between what is known and what we do in renal medicine:
improving implementability of the European Renal Best Practice guidelines.
AB - The increasing volume of evidence on how to treat kidney patients makes it
difficult for nephrologists and renal nurses to keep up-to-date. This potentially
widens the gap between what is known about best practice and how daily renal care
is provided. Rigorously developed clinical practice guidelines can be important
tools to bridge this gap. However, just developing and publishing guidelines does
not ensure their use in actual practice. In this paper, we distinguish and
illustrate three types of modifiable factors (i.e. barriers) that potentially
impede renal healthcare professionals to provide care according to the
guidelines: barriers related to knowledge, to attitudes and to behaviour.
European Renal Best Practice (ERBP) produces guidelines for care of kidney
patients in Europe and neighbouring regions. To facilitate implementation of its
guidelines, ERBP aims to optimize 'guideline implementability', which regards the
intrinsic characteristics of guidelines (i.e. format and content). The last
section of this paper describes some of the associated ERBP activities, which are
planned or pending.
PMID- 24353323
TI - Invariant natural killer T cells are depleted in renal impairment and recover
after kidney transplantation.
AB - BACKGROUND: Altered immune function in patients with renal failure results in
both susceptibility to infection and increased inflammatory response. Invariant
natural killer T (iNKT) cells are a conserved, immunoregulatory T lymphocyte
subset that responds to lipid antigens with near-immediate cytokine production
and cytotoxicity. iNKT cells are required for the antibacterial host response.
Whether renal failure and renal replacement therapy alter iNKT cell abundance or
phenotype has not been investigated. METHODS: iNKT cells were studied by flow
cytometry in the peripheral blood of patients with acute renal failure, chronic
haemo- and peritoneal dialysis (PD), chronic kidney disease and after renal
transplantation. RESULTS: A very marked reduction in iNKT lymphocytes was found
in acute renal failure before the first haemodialysis (HD) session. iNKT cells
were depleted in end-stage renal disease patients receiving either HD or PD. iNKT
cell depletion was accentuated after an HD session. Lesser degrees were observed
in patients with non-dialysis-dependent chronic kidney disease. CD56 and CD161 NK
cell marker expression was decreased in renal impairment. CD56(+) and CD161(+)
iNKT cells produced more interferon-gamma than negative cells of the same donor.
Within the first year after kidney transplantation, the decrease in iNKT cells
and their NK cell markers was reverted. CONCLUSIONS: We describe for the first
time that iNKT lymphocytes are reduced in end-stage renal disease and further
depleted by HD. iNKT cells are important for early host response including
activation of other immune cells and their depletion may contribute to immune
dysfunction in renal disease.
PMID- 24353324
TI - Magnesium loss in cyclosporine-treated patients is related to renal epidermal
growth factor downregulation.
AB - BACKGROUND: Cyclosporine (CsA) treatment is associated with hypomagnesaemia due
to a renal Mg(2+) leak. In animal studies a role for the Mg(2+) channel TRPM6
localized in the distal convoluted tubule and stimulated by epidermal growth
factor (EGF) is suggested. We hypothesize that CsA-induced hypomagnesaemia is due
to a renal magnesium leak, also in patients, resulting from a downregulation of
the renal EGF production, thereby inhibiting the activation of TRPM6. METHODS:
Renal transplant patients treated with CsA (n = 55) and 35 chronic kidney disease
(CKD) patients were included. At three time points, with an interval of at least
1 month, blood and urine samples were taken to determine creatinine, Mg(2+),
sodium and EGF. RESULTS: Serum Mg(2+) was significantly lower in the CsA group
versus the CKD group with significantly more CsA-treated patients developing
hypomagnesaemia. Although the fractional excretion (FE) Mg(2+) did not differ
significantly between the two groups, subanalysis of the patients with
hypomagnesaemia showed a significantly higher FE Mg(2+) in CsA-treated patients
compared with CKD patients (P = 0.05). The urinary EGF excretion was
significantly decreased in the CsA group and was a predictor of the FE Mg(2+) in
the two groups. Serum sodium was significantly decreased in the CsA group
simultaneously with an increased FE Na(+). CONCLUSIONS: In CsA-treated patients,
the association of a low urinary EGF excretion and a decreased renal Mg(2+)
reabsorption is in accordance with in vitro and animal studies. In the whole
study population, log urinary EGF excretion is an independent predictor of the FE
Mg(2+), supporting the role of EGF in magnesium reabsorption.
PMID- 24353326
TI - Challenging cytomegalovirus data in glioblastoma.
PMID- 24353328
TI - Pipeline endovascular reconstruction of traumatic dissecting aneurysms of the
intracranial internal carotid artery.
AB - A 22-year-old woman was involved in a motor vehicle collision resulting in
multiple facial fractures and extensive internal carotid artery (ICA) injury
including a right carotid-cavernous fistula, complex dissection flap and
dissecting aneurysms. Endovascular coil embolization was initially performed to
treat the cavernous carotid fistula and then again on two separate occasions to
treat expanding dissecting aneurysms. Parent vessel reconstruction of the right
ICA was subsequently performed with the Pipeline embolization device, resulting
in complete anatomical restoration of this vessel.
PMID- 24353327
TI - Cerebral arteriopathy associated with Arg179His ACTA2 mutation.
AB - ACTA2 mutations have recently been shown to cause a multisystem smooth muscle
dysfunction syndrome that may result in pediatric stroke. We report a case of
ACTA2 mutation in a 3-year-old girl presenting with acute ischemic stroke and
provide high resolution imaging of the cerebral arteries demonstrating novel
findings of multiple tiny aneurysms (particularly in the posterior circulation),
as well as the more characteristic imaging phenotype of straightened and narrowed
proximal intracranial vessels, dilated cervical vessels and occlusion of the M1
MCA segment without lenticulostriate collateral formation. This newly identified
disease should be added to the differential diagnosis of pediatric stroke and
cerebral vasculopathy. Neuroradiologists, interventionalists, surgeons and
neurologists should become familiar with this rare disease and its clinical
sequelae.
PMID- 24353325
TI - Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is
associated with 9p loss, genomic instability, and angiogenic gene expression.
AB - BACKGROUND: The aim of this study was to correlate MRI features and molecular
characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI
characteristics of 50 AO patients enrolled in the French national network for
high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH
mutational statuses were assessed using high-resolution single-nucleotide
polymorphism arrays and direct sequencing, respectively. The gene expression
profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.
RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but
the radiological presentations of these cases were heterogeneous, ranging from
low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The
1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P =
.001), with heterogeneous intratumoral signal intensities (P = .003) and with no
or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7)
more frequently displayed ringlike contrast enhancements (P = .03) and were more
frequently located outside of the frontal lobe (P = .01). However, no specific
imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH
mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was
associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A
loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene
expression (P < .001), particularly for vascular endothelial growth factor A and
angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation
are associated with preferential (but not with specific) imaging characteristics.
Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional
molecular alterations, especially chromosome 9p loss, which is associated with
contrast enhancement and larger tumor volume.
PMID- 24353329
TI - Posterior fossa dural arteriovenous fistula presenting clinically as a carotid
cavernous fistula treated by a direct access cavernous sinus approach.
AB - Dural arteriovenous fistulas (dAVFs) represent approximately 10-15% of all
cerebral vascular malformations. Although dAVFs can occur anywhere in the brain,
they occur most frequently in the cavernous and transverse-sigmoid sinuses.
Posterior fossa dAVFs presenting clinically as carotid-cavernous fistulae (CCF)
are rarely encountered in clinical practice. We discuss and illustrate an unusual
case of a left posterior fossa dAVF that presented clinically with chemosis and
early visual impairment, similar to that of CCF. This was subsequently treated by
a direct access cavernous sinus approach. We describe the technique used to
access the cavernous sinus directly in cases where conventional transvenous and
transarterial routes have been exhausted.
PMID- 24353330
TI - Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with
infarct growth and clinical outcome.
AB - OBJECTIVE: To understand how three commonly used measures of endovascular therapy
correlate with clinical outcome and infarct growth. METHODS: Prospectively
enrolled patients underwent baseline MRI and started endovascular therapy within
12 h of stroke onset. The final angiogram was given a primary arterial occlusive
lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction
(TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3).
The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and
TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients
were classified according to whether or not they had target mismatch (TMM). Good
outcome was defined as a 90-day modified Rankin Scale score of 0-2. RESULTS:
Endovascular treatment was attempted in 100. A good outcome was achieved in 57%
of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of
0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower
rates of good outcome (44% and 47%, respectively), which were not significantly
better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with
TMM, these rates of good outcome improved with all the scoring systems and were
significantly better for TIMI and TICI scores. Patients with a TICI score of 2a
had rates of good functional outcome and lesion growth which were not different
from those with TICI scores of 0-1 but were significantly worse than those with
TICI scores of 2b-3. CONCLUSIONS: TIMI 2-3 and TICI 2b-3 reperfusion scores
demonstrated improved outcome in patients with tissue mismatch with a small
infarct core and a larger hypoperfused region but AOL scores did not. Patients
with a TICI score of 2a had a poorer outcome and more lesion growth than those
with TICI scores of 2b-3.
PMID- 24353331
TI - Variability in initial response to standard clopidogrel therapy, delayed
conversion to clopidogrel hyper-response, and associated thromboembolic and
hemorrhagic complications in patients undergoing endovascular treatment of
unruptured cerebral aneurysms.
AB - BACKGROUND AND PURPOSE: Variability in response to clopidogrel therapy is
increasingly being recognized as an important factor in thromboembolic and
hemorrhagic complications encountered after neurointerventional procedures. This
study aims to determine the variability in response to clopidogrel therapy and
associated complications in patients undergoing endovascular treatment of
unruptured cerebral aneurysms. METHODS: We recorded baseline patient
characteristics, co-administered medications, P2Y12 reaction units (PRU) values
with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic
complications in patients undergoing endovascular treatment of unruptured
cerebral aneurysms at our institution during a 19 month period. RESULTS: 100
patients were included in the study, 76 women and 24 men, mean age 57.3 years. 15
patients exhibited an initial clopidogrel hypo-response (PRU >240) and 21
patients an initial clopidogrel hyper-response (PRU <60). 36 patients had a
follow-up VerifyNow test performed without changes to the standard 75 mg daily
clopidogrel dose, which demonstrated that 59% of patients who had initially been
within the target 60-240 PRU range exhibited a delayed conversion to clopidogrel
hyper-response. In our cohort, a clopidogrel hypo-response was associated with a
significantly increased risk of thromboembolic complications in patients
undergoing cerebral aneurysm treatment with stent assistance or the pipeline
embolization device (60%, p=0.003), while a clopidogrel hyper-response was
associated with a significantly increased risk of major hemorrhagic complications
in all patients undergoing endovascular treatment of cerebral aneurysms (11%,
p=0.016). CONCLUSIONS: We found wide and dynamic variability in response to
clopidogrel therapy in patients undergoing endovascular treatment of unruptured
cerebral aneurysms, which was significantly associated with thromboembolic and
major hemorrhagic complications in our cohort.
PMID- 24353332
TI - In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by
FTLD pathology.
AB - OBJECTIVE: To identify early cognitive and neuroimaging features of sporadic
nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by
frontotemporal lobar degeneration (FTLD) subtypes. METHODS: We prospectively
collected clinical, neuroimaging, and neuropathologic data in 11 patients with
sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD-transactive response
DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed
patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at
presentation in the whole group and in each pathologic subtype separately. We
also considered longitudinal clinical data. RESULTS: At first evaluation,
regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most
common cognitive feature and atrophy involved the left posterior frontal lobe.
Each pathologic subtype showed few distinctive features. At presentation,
patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria
with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of
the left posterior frontal regions and in left frontal WM. While speech and
language deficits were prominent early, within 3 years of symptom onset, all
patients with nfvPPA-tau developed significant extrapyramidal motor signs. At
presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic
features, mild agrammatism, and atrophy in left posterior frontal GM only.
Selective mutism occurred early, when general neurologic examination only showed
mild decrease in finger dexterity in the right hand. CONCLUSIONS: Clinical
features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration
of GM and WM in frontal motor speech and language networks. We propose that early
WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM
loss might be indicative of FTLD-TDP.
PMID- 24353334
TI - Tongue pressure as a novel biomarker of spinal and bulbar muscular atrophy.
AB - OBJECTIVE: This study aimed to explore the reliability and validity of tongue
pressure measurement as a quantitative evaluation of swallowing function in
patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This study
enrolled 47 genetically confirmed patients with SBMA and 38 age- and sex-matched
healthy controls. In both groups we measured tongue pressure using an intraoral
pressure probe and assessed questionnaires that evaluated swallowing functions.
We then analyzed the relationship between tongue pressure, functional scales, and
the muscle weakness of other regions. RESULTS: Levels of tongue pressure were
decreased in patients with SBMA within 3 years from the onset of the disease
compared to healthy controls (SBMA 15.3 +/- 6.4 kPa; healthy controls 37.3 +/-
9.6 kPa; p < 0.001). Test-retest analysis showed a high reliability in patients
with SBMA (intraclass correlation coefficient = 0.986). Tongue pressure showed a
strong correlation with bulbar-related functional scales. Decrease of tongue
pressure was detected in patients who reported no subjective dysphagia, and
repetition of swallowing compensated for tongue weakness in such subjects. In
patients with SBMA, tongue pressure more strongly correlates with the strength of
pharyngeal, neck, and upper limb musculatures than with that of the lower limbs.
CONCLUSION: Tongue pressure measurement is reliable and reflects swallowing
function in patients with SBMA. The muscle strength of the tongue appears to
decrease in SBMA before the awareness of subjective dysphagia, suggesting that
tongue pressure measurement is a novel biomarker of SBMA and is applicable to
early-stage detection.
PMID- 24353333
TI - Higher risk of progression to dementia in mild cognitive impairment cases who
revert to normal.
AB - OBJECTIVE: To estimate rates of progression from mild cognitive impairment (MCI)
to dementia and of reversion from MCI to being cognitively normal (CN) in a
population-based cohort. METHODS: Participants (n = 534, aged 70 years and older)
enrolled in the prospective Mayo Clinic Study of Aging were evaluated at baseline
and every 15 months to identify incident MCI or dementia. RESULTS: Over a median
follow-up of 5.1 years, 153 of 534 participants (28.7%) with prevalent or
incident MCI progressed to dementia (71.3 per 1,000 person-years). The cumulative
incidence of dementia was 5.4% at 1 year, 16.1% at 2, 23.4% at 3, 31.1% at 4, and
42.5% at 5 years. The risk of dementia was elevated in MCI cases (hazard ratio
[HR] 23.2, p < 0.001) compared with CN subjects. Thirty-eight percent (n = 201)
of MCI participants reverted to CN (175.0/1,000 person-years), but 65%
subsequently developed MCI or dementia; the HR was 6.6 (p < 0.001) compared with
CN subjects. The risk of reversion was reduced in subjects with an APOE epsilon4
allele (HR 0.53, p < 0.001), higher Clinical Dementia Rating Scale-Sum of Boxes
(HR 0.56, p < 0.001), and poorer cognitive function (HR 0.56, p < 0.001). The
risk was also reduced in subjects with amnestic MCI (HR 0.70, p = 0.02) and
multidomain MCI (HR 0.61, p = 0.003). CONCLUSIONS: MCI cases, including those who
revert to CN, have a high risk of progressing to dementia. This suggests that
diagnosis of MCI at any time has prognostic value.
PMID- 24353335
TI - Predicting dementia in Parkinson disease by combining neurophysiologic and
cognitive markers.
AB - OBJECTIVE: To assess the ability of neurophysiologic markers in conjunction with
cognitive assessment to improve prediction of progression to dementia in
Parkinson disease (PD). METHODS: Baseline cognitive assessments and
magnetoencephalographic recordings from 63 prospectively included PD patients
without dementia were analyzed in relation to PD-related dementia (PDD)
conversion over a 7-year period. We computed Cox proportional hazard models to
assess the risk of converting to dementia conveyed by cognitive and
neurophysiologic markers in individual as well as combined risk factor analyses.
RESULTS: Nineteen patients (30.2%) developed dementia. Baseline cognitive
performance and neurophysiologic markers each individually predicted conversion
to PDD. Of the cognitive test battery, performance on a posterior (pattern
recognition memory score < median; hazard ratio (HR) 6.80; p = 0.001) and a
fronto-executive (spatial span score < median; HR 4.41; p = 0.006) task most
strongly predicted dementia conversion. Of the neurophysiologic markers, beta
power < median was the strongest PDD predictor (HR 5.21; p = 0.004), followed by
peak frequency < median (HR 3.97; p = 0.016) and theta power > median (HR 2.82; p
= 0.037). In combination, baseline cognitive performance and neurophysiologic
measures had even stronger predictive value, with the combination of impaired
fronto-executive task performance and low beta power being associated with the
highest dementia risk (both risk factors vs none: HR 27.3; p < 0.001).
CONCLUSIONS: Combining neurophysiologic markers with cognitive assessment can
substantially improve dementia risk profiling in PD, providing potential benefits
for clinical care as well as for the future development of therapeutic
strategies.
PMID- 24353336
TI - Effect of subthalamic nucleus deep brain stimulation on driving in Parkinson
disease.
AB - OBJECTIVE: To examine the influence of subthalamic nucleus (STN) deep brain
stimulation (DBS) on driving in patients with Parkinson disease (PD). METHODS:
Using a driving simulator setup proven to reflect on-road driving, 2 main
analyses were performed: 1) comparison of driving performance among 23 patients
with deep brain surgery (DBS patients), 21 patients without surgery (no-DBS
patients), and 21 controls; and 2) analysis of the effect of stimulation vs
levodopa on driving performance. To this end, 3 tests were run in the medicated
DBS patient cohort, with 3 different conditions: "stimulation on" (STIM) (equated
to daily treatment), "stimulation off" (OFF), and "stimulation off/levodopa" (LD)
(dosage aimed at maintaining motor status). Differences in driving times and
errors among conditions were analyzed. RESULTS: Age and cognitive deficits
influenced driving performance negatively. The no-DBS patient group performed
worse in driving time and driving errors than controls. DBS patients drove slower
than controls and no-DBS patients. Driving safety was comparable to controls but
higher than in no-DBS patients. Within the DBS patient group, driving was more
accurate with STIM than with LD, although motor effects did not differ. Driving
with STIM, but not with LD, was superior to driving in the OFF condition.
CONCLUSION: DBS of the STN seems to have a beneficial effect on driving ability
in patients with PD, potentially because of nonmotor driving-relevant aspects.
Our data suggest that driving permission for DBS-treated patients with PD should
not be handled more restrictively than permissions for patients with PD in
general. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
STN-DBS in patients with PD is associated with a reduction in driving errors and
improvements in driving accuracy in driving simulations.
PMID- 24353337
TI - Development of movement-related intracortical inhibition in acute to chronic
subcortical stroke.
AB - OBJECTIVE: A prospective longitudinal cohort study in stroke patients was
performed to better understand the role of gamma-aminobutyric acid-dependent
intracortical inhibition (ICI) for recovery after stroke. METHODS: Patients with
acute first-ever subcortical stroke and hand paresis were recruited, and motor
function as well as ICI were measured up to 1 year after stroke. Motor recovery
was defined as the change in hand motor function from the acute to the chronic
stage (Delta = recovery over 1 year). Primary outcome measures for hand motor
function were the recovery of grip strength (DeltaGS) and finger-tapping speed
(DeltaFT). Using double-pulse transcranial magnetic stimulation, we studied ICI
in the ipsilesional primary motor cortex during the preparation of a movement
with the paretic hand at different time points during recovery (first week, 7
weeks, 3 months, and 1 year after stroke). RESULTS: Eleven patients were enrolled
(mean age 62.9 +/- 3.8 years). The results of a multiple regression analysis
showed a significant association of movement-related ICI in the acute stage only
(first week) with motor recovery over 1 year (DeltaGS: R(2) = 0.75, F = 17.6, p =
0.006; DeltaFT: R(2) = 0.55, F = 7.3, p = 0.035). More disinhibition of ICI in
the acute phase of stroke predicted more improvement in DeltaGS (beta = -0.86, p
= 0.006) and DeltaFT (beta = -0.74, p = 0.035), independent of the initial motor
deficit. CONCLUSIONS: Movement-related ICI one week after a subcortical stroke is
associated with better outcome of hand motor function. Disinhibition in the
ipsilesional primary motor cortex could be a mechanism of how the brain attempts
to promote motor recovery after stroke.
PMID- 24353338
TI - Risk of dementia after fluctuating mild cognitive impairment: when the yo-yoing
stops.
AB - Friends, family members, and medical caretakers notice that sometimes we have
good days and sometimes we have bad days. If we are older, the bad days may
involve making poor judgments, acting impulsively, forgetting information we just
heard, or repeating ourselves in conversations. If these oscillations persist,
then someone we know well may suggest consulting a physician because our bad days
are interfering with our daily activities. Presented with variable symptoms on
different occasions, physicians legitimately may diagnose us with mild cognitive
impairment (MCI) on one occasion and then equally legitimately retract the
diagnosis on another occasion. Many in the field have observed that patients and
study participants may yo-yo between normal cognitive performance and MCI, but
until now, the import of these diagnostic fluctuations was unclear.
PMID- 24353339
TI - PET imaging shows loss of striatal PDE10A in patients with Huntington disease.
AB - Phosphodiesterase 10A (PDE10A) belongs to a family of enzymes that hydrolyze
cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate.(1)
PDE10A is highly enriched in striatal medium spiny neurons (MSNs), where it
regulates intracellular signaling.(1) PDE10A has been proposed as a therapeutic
target for Huntington disease (HD), a disorder that preferentially affects MSNs,
based on the observation that pharmacologic inhibition of PDE10A in transgenic HD
mice significantly improved behavioral and neuropathologic abnormalities.(2)
However, earlier work had shown that striatal PDE10A levels in HD mice already
decline to minimal levels before onset of motor symptoms,(3) possibly because
mutant huntingtin represses PDE10A transcription. Also, postmortem analysis of
striatum of 3 patients with HD revealed strong reduction of PDE10A levels.(3)
Depletion of PDE10A in HD striatum would at first sight seem hard to reconcile
with a beneficial effect of PDE10A inhibitors in HD. However, a recent study
reported a dramatic increase, rather than decrease, of PDE10A protein in MSNs of
HD mice.(4) In light of these conflicting results and the strong interest in
development of PDE10A inhibitors for clinical use in HD, it is important to
determine whether PDE10A levels are affected in the striatum of patients with HD
in vivo.
PMID- 24353341
TI - "How much will I recover, doctor?" Some help with an ever-elusive answer.
PMID- 24353340
TI - Practical utility of amyloid and FDG-PET in an academic dementia center.
AB - OBJECTIVE: To evaluate the effect of amyloid imaging on clinical decision making.
METHODS: We conducted a retrospective analysis of 140 cognitively impaired
patients (mean age 65.0 years, 46% primary beta-amyloid (Abeta) diagnosis, mean
Mini-Mental State Examination 22.3) who underwent amyloid (Pittsburgh compound B
[PiB]) PET as part of observational research studies and were evaluated
clinically before and after the scan. One hundred thirty-four concurrently
underwent fluorodeoxyglucose (FDG)-PET. We assessed for changes between the pre-
and post-PET clinical diagnosis (from Abeta to non-Abeta diagnosis or vice versa)
and Alzheimer disease treatment plan. The association between PiB/FDG results and
changes in management was evaluated using chi(2) and multivariate logistic
regression. Postmortem diagnosis was available for 24 patients (17%). RESULTS:
Concordance between scan results and baseline diagnosis was high (PiB 84%, FDG
82%). The primary diagnosis changed after PET in 13/140 patients (9%) overall but
in 5/13 (38%) patients considered pre-PET diagnostic dilemmas. When examined
independently, discordant PiB and discordant FDG were both associated with
diagnostic change (unadjusted p < 0.0001). However, when examined together in a
multivariate logistic regression, only discordant PiB remained significant
(adjusted p = 0.00013). Changes in treatment were associated with discordant PiB
in patients with non-Abeta diagnoses (adjusted p = 0.028), while FDG had no
effect on therapy. Both PiB (96%) and FDG (91%) showed high agreement with
autopsy diagnosis. CONCLUSIONS: PET had a moderate effect on clinical outcomes.
Discordant PiB had a greater effect than discordant FDG, and influence on
diagnosis was greater than on treatment. Prospective studies are needed to better
characterize the clinical role of amyloid PET.
PMID- 24353342
TI - Clinical significance of early smoking withdrawal effects and their relationships
with nicotine metabolism: preliminary results from a pilot study.
AB - INTRODUCTION: Although the early time course of smoking withdrawal effects has
been characterized, the clinical significance of early withdrawal symptoms and
their predictors are unknown. This study evaluated the relationships of early
smoking withdrawal effects with quit attempt outcomes and the rate of nicotine
metabolism. METHODS: Eleven treatment-seeking smokers abstained from smoking for
4 hr in the laboratory before a quit attempt. Withdrawal measures included heart
rate, sustained attention, and self-report. Following baseline assessment,
withdrawal measures were administered every 30 min. At the conclusion of the 4-hr
early withdrawal session, participants received a brief smoking cessation
intervention and then returned 1 week and 12 weeks later for outcome assessments
that included biochemically confirmed smoking abstinence, cigarettes smoked in
the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine
metabolism was estimated at intake with the nicotine metabolite ratio (trans-3'
hydroxycotinine/cotinine) measured in saliva. RESULTS: Greater self-reported
negative affect and concentration difficulty during early withdrawal, most
notably anxiety, were related with poorer quit attempt outcomes. There was some
indication that although a faster increase in craving and greater hunger during
early withdrawal were associated with more favorable outcomes, a greater decrease
in heart rate during this time was associated with poorer outcomes. Faster
nicotine metabolism was related to a faster increase in anxiety but a slower
increase in craving during early withdrawal. CONCLUSIONS: These findings lend
support to the clinical significance of early smoking withdrawal effects. The
rate of nicotine metabolism may be a useful predictor of early withdrawal
symptoms.
PMID- 24353343
TI - Dietary flavonoids from modified apple reduce inflammation markers and modulate
gut microbiota in mice.
AB - Apples are rich in polyphenols, which provide antioxidant properties, mediation
of cellular processes such as inflammation, and modulation of gut microbiota. In
this study we compared genetically engineered apples with increased flavonoids
[myeloblastis transcription factor 10 (MYB10)] with nontransformed apples from
the same genotype, "Royal Gala" (RG), and a control diet with no apple. Compared
with the RG diet, the MYB10 diet contained elevated concentrations of the
flavonoid subclasses anthocyanins, flavanol monomers (epicatechin) and oligomers
(procyanidin B2), and flavonols (quercetin glycosides), but other plant secondary
metabolites were largely unaltered. We used these apples to investigate the
effects of dietary flavonoids on inflammation and gut microbiota in 2 mouse
feeding trials. In trial 1, male mice were fed a control diet or diets
supplemented with 20% MYB10 apple flesh and peel (MYB-FP) or RG apple flesh and
peel (RG-FP) for 7 d. In trial 2, male mice were fed MYB-FP or RG-FP diets or
diets supplemented with 20% MYB10 apple flesh or RG apple flesh for 7 or 21 d. In
trial 1, the transcription levels of inflammation-linked genes in mice showed
decreases of >2-fold for interleukin-2 receptor (Il2rb), chemokine receptor 2
(Ccr2), chemokine ligand 10 (Cxcl10), and chemokine receptor 10 (Ccr10) at 7 d
for the MYB-FP diet compared with the RG-FP diet (P < 0.05). In trial 2, the
inflammation marker prostaglandin E(2) (PGE(2)) in the plasma of mice fed the MYB
FP diet at 21 d was reduced by 10-fold (P < 0.01) compared with the RG-FP diet.
In colonic microbiota, the number of total bacteria for mice fed the MYB-FP diet
was 6% higher than for mice fed the control diet at 21 d (P = 0.01). In summary,
high-flavonoid apple was associated with decreases in some inflammation markers
and changes in gut microbiota when fed to healthy mice.
PMID- 24353344
TI - Antioxidant supplements reduced oxidative stress and stabilized liver function
tests but did not reduce inflammation in a randomized controlled trial in obese
children and adolescents.
AB - Oxidative stress and low-grade systemic inflammation may contribute to the
pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver
disease. Increasing intake of dietary antioxidants might be beneficial, but there
are few data in obese children. To examine the effect of antioxidant
supplementation on biomarkers of oxidative stress, inflammation, and liver
function, we randomly assigned overweight or obese children and adolescents (n =
44; mean +/- SD age: 12.7 +/- 1.5 y) participating in a lifestyle modification
program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU;
vitamin C, 500 mg; selenium, 50 MUg) or placebo. We measured anthropometrics,
antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane
metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid
profile at baseline and endpoint. There was a significant treatment effect of
antioxidant supplementation on antioxidant status [alpha-tocopherol, beta = 23.2
(95% CI: 18.0, 28.4); ascorbic acid, beta = 70.6 (95% CI: 51.7, 89.4); selenium,
beta = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin
F2alpha, beta = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory
markers measured. There was a significant treatment effect on alanine
aminotransferase [beta = -0.13 (95% CI: -0.23, -0.03)], a trend toward a
significant effect on aspartate aminotransferase [beta = -0.04 (95% CI: -0.09,
0.01)], and no significant effect on gamma-glutamyltransferase [beta = -0.03 (95%
CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved
antioxidant-oxidant balance and modestly improved liver function tests; however,
it did not reduce markers of systemic inflammation despite significant baseline
correlations between oxidative stress and inflammation. The study was registered
at clinicaltrials.gov as NCT01316081.
PMID- 24353345
TI - Cognitive performance in older adults is inversely associated with fish
consumption but not erythrocyte membrane n-3 fatty acids.
AB - Higher n-3 (omega-3) polyunsaturated fatty acids (PUFAs) and fish intake may help
maintain cognitive function in older age. However, evidence is inconsistent; few
studies have examined the relation in cognitively healthy individuals across
numerous cognitive domains, and none to our knowledge have considered lifetime
fish intake. We examined associations between multiple domains of cognition and
erythrocyte membrane n-3 PUFA proportions and historical and contemporary fish
intake in 390 normal older adults, analyzing baseline data from the Older People,
Omega-3, and Cognitive Health trial. We measured n-3 PUFA in erythrocyte
membranes, and we assessed historical and contemporary fish intake by food
frequency questionnaires. We assessed cognitive performance on reasoning, working
memory, short-term memory, retrieval fluency, perceptual speed, simple/choice
reaction time, speed of memory-scanning, reasoning speed, inhibition, and
psychomotor speed. Cognitive outcomes for each construct were factor scores from
confirmatory factor analysis. Multiple linear regression models controlled for a
number of potential confounding factors, including age, education, sex,
apolipoprotein E-epsilon 4 allele, physical activity, smoking, alcohol intake,
socioeconomic variables, and other health-related variables. Higher erythrocyte
membrane eicosapaentonoic acid proportions predicted slower perceptual and
reasoning speed in females, which was attenuated once current fish intake was
controlled. No other associations were present between n-3 PUFA proportions and
cognitive performance. Higher current fish consumption predicted worse
performance on several cognitive speed constructs. Greater fish consumption in
childhood predicted slower perceptual speed and simple/choice reaction time. We
found no evidence to support the hypothesis that higher proportions of long-chain
n-3 fatty acids or fish intake benefits cognitive performance in normal older
adults.
PMID- 24353346
TI - Low and high dietary protein:carbohydrate ratios during pregnancy affect materno
fetal glucose metabolism in pigs.
AB - Inadequate dietary protein during pregnancy causes intrauterine growth
retardation. Whether this is related to altered maternal and fetal glucose
metabolism was examined in pregnant sows comparing a high-protein:low
carbohydrate diet (HP-LC; 30% protein, 39% carbohydrates) with a moderately low
protein:high-carbohydrate diet (LP-HC; 6.5% protein, 68% carbohydrates) and the
isoenergetic standard diet (ST; 12.1% protein, 60% carbohydrates). During late
pregnancy, maternal and umbilical glucose metabolism and fetal hepatic mRNA
expression of gluconeogenic enzymes were examined. During an i.v. glucose
tolerance test (IVGTT), the LP-HC-fed sows had lower insulin concentrations and
area under the curve (AUC), and higher glucose:insulin ratios than the ST- and
the HP-LC-fed sows (P < 0.05). Insulin sensitivity and glucose clearance were
higher in the LP-HC sows compared with ST sows (P < 0.05). Glucagon
concentrations during postabsorptive conditions and IVGTT, and glucose AUC during
IVGTT, were higher in the HP-LC group compared with the other groups (P < 0.001).
(13)C glucose oxidation was lower in the HP-LC sows than in the ST and LP-HC sows
(P < 0.05). The HP-LC fetuses were lighter and had a higher brain:liver ratio
than the ST group (P < 0.05). The umbilical arterial inositol concentration was
greater in the HP-LC group (P < 0.05) and overall small fetuses (230-572 g) had
higher values than medium and heavy fetuses (>=573 g) (P < 0.05). Placental
lactate release was lower in the LP-HC group than in the ST group (P < 0.05).
Fetal glucose extraction tended to be lower in the LP-HC group than in the ST
group (P = 0.07). In the HP-LC and LP-HC fetuses, hepatic mRNA expression of
cytosolic phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase
(G6PC) was higher than in the ST fetuses (P < 0.05). In conclusion, the HP-LC and
LP-HC sows adapted by reducing glucose turnover and oxidation and having higher
glucose utilization, respectively. The HP-LC and LP-HC fetuses adapted via
prematurely expressed hepatic gluconeogenic enzymes.
PMID- 24353348
TI - Schooling, Child Labor, and the Returns to Healthcare in Tanzania.
AB - We study the effects of accessing better healthcare on the schooling and labor
supply decisions of sick children in Tanzania. Using variation in the cost of
formal-sector healthcare to predict treatment choice, we show that accessing
better healthcare decreases length of illness and changes children's allocation
of time to school and work. Children attend school for more days per week-but not
for more hours per day-as a result of accessing better healthcare. There are no
significant effects on child labor, but the results suggest that time spent in
physically strenuous activities such as farming and herding increases.
PMID- 24353347
TI - Simulation and modelling of slip flow over surfaces grafted with polymer brushes
and glycocalyx fibres.
AB - Fabrication of functionalized surfaces using polymer brushes is a relatively
simple process and parallels the presence of glycocalyx filaments coating the
luminal surface of our vasculature. In this paper, we perform atomistic-like
simulations based on dissipative particle dynamics (DPD) to study both polymer
brushes and glycocalyx filaments subject to shear flow, and we apply mean-field
theory to extract useful scaling arguments on their response. For polymer
brushes, a weak shear flow has no effect on the brush density profile or its
height, while the slip length is independent of the shear rate and is of the
order of the brush mesh size as a result of screening by hydrodynamic
interactions. However, for strong shear flow, the polymer brush is penetrated
deeper and is deformed, with a corresponding decrease of the brush height and an
increase of the slip length. The transition from the weak to the strong shear
regime can be described by a simple 'blob' argument, leading to the scaling
gamma0 ? sigma3/2, where gamma0 is the critical transition shear rate and sigma
is the grafting density. Furthermore, in the strong shear regime, we observe a
cyclic dynamic motion of individual polymers, causing a reversal in the direction
of surface flow. To study the glycocalyx layer, we first assume a homogeneous
flow that ignores the discrete effects of blood cells, and we simulate
microchannel flows at different flow rates. Surprisingly, we find that, at low
Reynolds number, the slip length decreases with the mean flow velocity, unlike
the behaviour of polymer brushes, for which the slip length remains constant
under similar conditions. (The slip length and brush height are measured with
respect to polymer mesh size and polymer contour length, respectively.) We also
performed additional DPD simulations of blood flow in a tube with walls having a
glycocalyx layer and with the deformable red blood cells modelled accurately at
the spectrin level. In this case, a plasma cell-free layer is formed, with
thickness more than three times the glycocalyx layer. We then find our scaling
arguments based on the homogeneous flow assumption to be valid for this
physiologically correct case as well. Taken together, our findings point to the
opposing roles of conformational entropy and bending rigidity - dominant effects
for the brush and glycocalyx, respectively - which, in turn, lead to different
flow characteristics, despite the apparent similarity of the two systems.
PMID- 24353349
TI - Sisters' and Girlfriends' Sexual and Childbearing Behavior: Effects on Early
Adolescent Girls' Sexual Outcomes.
AB - This study examined three key issues related to the effects of sisters' and
girlfriends' sexual and childbearing behavior on early adolescent girls' sexual
outcomes. Subjects were 455 girls from predominantly minority racial backgrounds.
Results indicated that number of sexually active girlfriends, number of sexually
active sisters, and presence of an adolescent childbearing sister were positively
associated with permissive sexual attitudes, positive intentions for future
sexual activity, and a greater likelihood of being a nonvirgin. The strength of
these relationships did not vary by race, but there was a greater presence of
permissive social influences for African American girls than for nonblack girls.
Results from multiple hierarchical regression analyses indicated that having both
many sexually active girlfriends and an adolescent childbearing sister had
particularly strong effects on permissive sexual attitudes and a nonvirgin
status.
PMID- 24353350
TI - Racial and Ethnic Differences in Girls' Sexual, Marital, and Birth Expectations.
AB - This study examines potential racial and ethnic differences in early adolescent
girls' desired and perceived normative role timing and the extent to which
various socioeconomic and family factors and school and job aspirations might be
linked with girls' role-timing expectations. Using a racially and ethnically
diverse sample, (n = 574; 183 Hispanics, 177 Blacks, 93 Whites, and 70 Southeast
Asians; M age = 12.9), results indicated that young women of different races and
ethnicities saw their life course unfold in different sequences based on
different timetables and independent of their socioeconomic circumstances.
Hispanics desired rapid transitions at a young age, and Southeast Asians desired
more gradual transitions at an older age. Blacks perceived the greatest
likelihood of nonmarital childbearing for themselves, the longest normative
interval between first sex and first birth, but they desired the shortest
interval between first marriage and first birth. Within-race regressions revealed
that girls' future aspirations were important for their expected role timing,
even within the context of socioeconomic disadvantage (welfare receipt, low
family income). Findings suggest the importance of culture-specific age norms for
motivating role timing and role sequencing in young women's lives.
PMID- 24353351
TI - A spatial time-to-event approach for estimating associations between air
pollution and preterm birth.
AB - The paper describes a Bayesian spatial discrete time survival model to estimate
the effect of air pollution on the risk of preterm birth. The standard approach
treats prematurity as a binary outcome and cannot effectively examine time
varying exposures during pregnancy. Time varying exposures can arise either in
short-term lagged exposures due to seasonality in air pollution or long-term
cumulative exposures due to changes in length of exposure. Our model addresses
this challenge by viewing gestational age as time-to-event data where each
pregnancy becomes at risk at a prespecified time (e.g. the 28th week). The
pregnancy is then followed until either a birth occurs before the 37th week
(preterm), or it reaches the 37th week, and a full-term birth is expected. The
model also includes a flexible spatially varying baseline hazard function to
control for unmeasured spatial confounders and to borrow information across areal
units. The approach proposed is applied to geocoded birth records in Mecklenburg
County, North Carolina, for the period 2001-2005.We examine the risk of preterm
birth that is associated with total cumulative and 4-week lagged exposure to
ambient fine particulate matter.
PMID- 24353352
TI - Systematic coarse-graining of spectrin-level red blood cell models.
AB - We present a rigorous procedure to derive coarse-grained red blood cell (RBC)
models, which yield accurate mechanical response. Based on a semi-analytic theory
the linear and nonlinear elastic properties of healthy and infected RBCs in
malaria can be matched with those obtained in optical tweezers stretching
experiments. The present analysis predicts correctly the membrane Young's modulus
in contrast to about 50% error in predictions by previous models. In addition, we
develop a stress-free model which avoids a number of pitfalls of existing RBC
models, such as non-smooth or poorly controlled equilibrium shape and dependence
of the mechanical properties on the initial triangulation quality. Here we employ
dissipative particle dynamics for the implementation but the proposed model is
general and suitable for use in many existing continuum and particle-based
numerical methods.
PMID- 24353353
TI - Land use/cover classification in the Brazilian Amazon using satellite images.
AB - Land use/cover classification is one of the most important applications in remote
sensing. However, mapping accurate land use/cover spatial distribution is a
challenge, particularly in moist tropical regions, due to the complex biophysical
environment and limitations of remote sensing data per se. This paper reviews
experiments related to land use/cover classification in the Brazilian Amazon for
a decade. Through comprehensive analysis of the classification results, it is
concluded that spatial information inherent in remote sensing data plays an
essential role in improving land use/cover classification. Incorporation of
suitable textural images into multispectral bands and use of segmentation-based
method are valuable ways to improve land use/cover classification, especially for
high spatial resolution images. Data fusion of multi-resolution images within
optical sensor data is vital for visual interpretation, but may not improve
classification performance. In contrast, integration of optical and radar data
did improve classification performance when the proper data fusion method was
used. Of the classification algorithms available, the maximum likelihood
classifier is still an important method for providing reasonably good accuracy,
but nonparametric algorithms, such as classification tree analysis, has the
potential to provide better results. However, they often require more time to
achieve parametric optimization. Proper use of hierarchical-based methods is
fundamental for developing accurate land use/cover classification, mainly from
historical remotely sensed data.
PMID- 24353354
TI - Evidence for the formation of dynamically created pre-formed ions at the
interface of isotopically enriched thin films.
AB - A novel approach to elucidate the ionization mechanism for the [M + H]+ molecular
ion of organic molecules is investigated by molecular depth profiling of
isotopically enriched thin films. Using a model bi-layer film of phenylalanine
(PHE) and PHE-D8, the results show formation of an [M + D]+ molecular ion for the
non-enriched PHE molecule attributed to rearrangements of chemical damage due to
successive primary ion impacts. The [M + D]+ ion is observed at the interface for
19.9nm in the enriched-on-top system and 9.9nm for the enriched-on-bottom system.
This ion formation is direct evidence for dynamically created pre-formed ions as
a result of chemical damage rearrangement induced by previous primary ion
bombardment events.
PMID- 24353355
TI - EFFECTS OF RUMINATION AND INITIAL SEVERITY ON REMISSION TO COGNITIVE THERAPY FOR
DEPRESSION.
AB - Trait rumination, a tendency to focus on depressive symptoms and negative
information, is associated with longer and more severe episodes of depression.
This study examined whether trait rumination was also associated with initial
remission from unipolar depression in Cognitive Therapy, which we hypothesized
would target this coping style. Eighty one patients completed measures of
depressive severity and rumination before and after 16-20 sessions of
procedurally determined Cognitive Therapy. Pre-treatment rumination and severity
were generally associated with later initial remission and lower odds of
achieving remission. Limited evidence also suggested that for the most severe
patients, rumination was associated with earlier initial remission and greater
odds of achieving initial remission. Cognitive Therapy was associated with
significant reductions in both rumination and severity. Results suggest that 1)
pre-treatment assessment of rumination and severity could help to plan treatment
course and 2) Cognitive Therapy is associated with changes in cognitive coping
styles.
PMID- 24353356
TI - Adrenal Diagnostics: An Endocrinologist's Perspective focused on
Hyperaldosteronism.
AB - The era of sophisticated high resolution imaging with the consequent
identification of previously unrecognised adrenal masses (adrenal
incidentalomas), has emphasised the need for an appropriate biochemical approach
to define adrenal function. The focus of this testing is on catecholamines from
the adrenal medulla (testing that has been rendered relatively straightforward by
plasma metanephrine measurements) and the physiological corticosteroids, cortisol
and aldosterone, synthesised by the adrenal cortex. The diagnosis of
hypercortisolism remains a challenge and has been extensively reviewed. In the
context of hypertension and an adrenal incidentaloma, the exclusion of
hyperaldosteronism has an importance beyond simple blood pressure control. This
review focuses on the recommended approaches to both the diagnosis of
hyperaldosteronism and the characterisation of its aetiology. Monogenetic causes
of mineralocorticoid hypertension are discussed as are recent developments with
respect to both the molecular aetiology and the differential diagnosis of
aldosterone-producing adenomas.
PMID- 24353361
TI - Multiple Response System: Evaluation of Policy Change in North Carolina's Child
Welfare System.
AB - Systemic challenges within child welfare have prompted many states to explore new
strategies aimed at protecting children while meeting the needs of families, but
doing so within the confines of shrinking budgets. Differential Response has
emerged as a promising practice for low or moderate risk cases of child
maltreatment. This mixed methods evaluation explored various aspects of North
Carolina's differential response system, known as the Multiple Response System
(MRS), including: child safety, timeliness of response and case decision,
frontloading of services, case distribution, implementation of Child and Family
Teams, collaboration with community-based service providers and Shared Parenting.
Utilizing Child Protective Services (CPS) administrative data, researchers found
that compared to matched control counties, MRS: had a positive impact on child
safety evidenced by a decline in the rates of substantiations and re-assessments;
temporarily disrupted timeliness of response in pilot counties but had no effect
on time to case decision; and increased the number of upfront services provided
to families during assessment. Qualitative data collected through focus groups
with providers and phone interviews with families provided important information
on key MRS strategies, highlighting aspects that families and social workers like
as well as identifying areas for improvement. This information is useful for
continuous quality improvement efforts, particularly related to the development
of training and technical assistance programs at the state and local level.
PMID- 24353358
TI - In search of mechanisms associated with mesenchymal stem cell-based therapies for
acute kidney injury.
AB - Acute kidney injury (AKI) is classically described as a rapid loss of kidney
function. AKI affects more than 15% of all hospital admissions and is associated
with elevated mortality rates. Although many advances have occurred, intermittent
or continuous renal replacement therapies are still considered the best options
for reversing mild and severe AKI syndrome. For this reason, it is essential that
innovative and effective therapies, without side effects and complications, be
developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell
(MSC) based therapies have numerous advantages in helping to repair inflamed and
damaged tissues and are being considered as a new alternative for treating kidney
injuries. Numerous experimental models have shown that MSCs can act via
differentiation-independent mechanisms to help renal recovery. Essentially, MSCs
can secrete a pool of cytokines, growth factors and chemokines, express enzymes,
interact via cell-to-cell contacts and release bioagents such as microvesicles to
orchestrate renal protection. In this review, we propose seven distinct
properties of MSCs which explain how renoprotection may be conferred: 1) anti
inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells;
4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of
cellular reprogramming. In this context, these mechanisms, either individually or
synergically, could induce renal protection and functional recovery. This review
summarises the most important effects and benefits associated with MSC-based
therapies in experimental renal disease models and attempts to clarify the
mechanisms behind the MSC-related renoprotection. MSCs may prove to be an
effective, innovative and affordable treatment for moderate and severe AKI.
However, more studies need to be performed to provide a more comprehensive global
understanding of MSC-related therapies and to ensure their safety for future
clinical applications.
PMID- 24353357
TI - The de ritis ratio: the test of time.
AB - De Ritis described the ratio between the serum levels of aspartate transaminase
(AST) and alanine transaminase (ALT) almost 50 years ago. While initially
described as a characteristic of acute viral hepatitis where ALT was usually
higher than AST, other authors have subsequently found it useful in alcoholic
hepatitis, where AST is usually higher than ALT. These interpretations are far
too simplistic however as acute viral hepatitis can have AST greater than ALT,
and this can be a sign of fulminant disease, while alcoholic hepatitis can have
ALT greater than AST when several days have elapsed since alcohol exposure. The
ratio therefore represents the time course and aggressiveness of disease that
would be predicted from the relatively short half-life of AST (18 h) compared to
ALT (36 h). In chronic viral illnesses such as chronic viral hepatitis and
chronic alcoholism as well as non-alcoholic fatty liver disease, an elevated
AST/ALT ratio is predictive of long terms complications including fibrosis and
cirrhosis. There are methodological issues, particularly whether or not pyridoxal
phosphate is used in the transaminase assays, and although this can have specific
effects when patient samples are deficient in this vitamin, these method
differences generally have mild effects on the usefulness of the assays or the
ratio. Ideally laboratories should be using pyridoxal phosphate supplemented
assays in alcoholic, elderly and cancer patients who may be pyridoxine deplete.
Ideally all laboratories reporting abnormal ALT should also report AST and
calculate the De Ritis ratio because it provides useful diagnostic and prognostic
information.
PMID- 24353360
TI - Hypothalamic-pituitary-adrenal axis physiology and cognitive control of behavior
in stress inoculated monkeys.
AB - Monkeys exposed to stress inoculation protocols early in life subsequently
exhibit diminished neurobiological responses to moderate psychological stressors
and enhanced cognitive control of behavior during juvenile development compared
to non-inoculated monkeys. The present experiments extended these findings and
revealed that stress inoculated monkeys: (a) mount neurobiological responses
equivalent to non-inoculated monkeys when the stressor is of sufficient
intensity, and (b) continue to exhibit enhanced cognitive control as young adults
compared to non-inoculated monkeys. These results suggest that stress inoculation
protocols alter the appraisal of and response to moderate stressors as less
threatening and permanently enhance cognitive control, at least through early
adulthood. These data therefore support the notion that the stress inoculation
phenotype reflects stress resilience rather than stress pathology.
PMID- 24353362
TI - Youths' Caretaking of Their Adolescent Sisters' Children: Results From Two
Longitudinal Studies.
AB - The extent and experiences of youths' caretaking of their adolescent sisters'
children have been assessed in two longitudinal studies. The first study examines
the caretaking patterns of 132 Latino and African American youth during middle
and late adolescence. The second study involves 110 Latino youth whose teenage
sister has recently given birth. Youth are studied at 6 weeks and 6 months
postpartum. In both studies, girls provide more hours of care than boys, and in
Study 1, girls' hours of care significantly increase with age whereas boys' hours
of caretaking decrease. Girls provide more care when their sisters are older and
when their mothers provide many hours of care, whereas boys provide less care
when their mothers provide more care and when they have many siblings. Results of
both studies reveal age, gender, and across-time differences in the extent of
care, type of caretaking activities, and experiences in providing care.
PMID- 24353364
TI - Conformational Properties of 1-Halogenated-1-Silacyclohexanes, C5H10SiHX (X = Cl,
Br, I): Gas Electron Diffraction, Low-Temperature NMR, Temperature-Dependent
Raman Spectroscopy, and Quantum-Chemical Calculations.
AB - The molecular structures of axial and equatorial conformers of cyclo-C5H10SiHX (X
= Cl, Br, I) as well as the thermodynamic equilibrium between these species was
investigated by means of gas electron diffraction, dynamic nuclear magnetic
resonance, temperature-dependent Raman spectroscopy, and quantum-chemical
calculations applying CCSD(T), MP2, and DFT methods. According to the
experimental and calculated results, all three compounds exist as a mixture of
two chair conformers of the six-membered ring. The two chair forms of Cs symmetry
differ in the axial or equatorial position of the X atom. In all cases, the axial
conformer is preferred over the equatorial one. When the experimental
uncertainties are taken into account, all of the experimental and theoretical
results for the conformational energy (Eaxial - Eequatorial) fit into a
remarkably narrow range of -0.50 +/- 0.15 kcal mol-1. It was found by NBO
analysis that the axial conformers are unfavorable in terms of steric energy and
conjugation effects and that they are stabilized mainly by electrostatic
interactions. The conformational energies for C6H11X and cyclo-C5H10SiHX (X = F,
Cl, Br, I, At) were compared using CCSD(T) calculations. In both series, fluorine
is predicted to have a lower conformational preference (cyclohexane equatorial,
silacyclohexane axial) than Cl, Br, and I. It is predicted that astatine would
behave very similarly to Cl, Br, and I within each series.
PMID- 24353363
TI - Strengthening Incarcerated Families: Evaluating a Pilot Program for Children of
Incarcerated Parents and Their Caregivers.
AB - Parental incarceration can be devastating for families. Children may experience
difficulties, and the stress on caregivers who take on unexpected childrearing is
high. We implemented and evaluated a family-level intervention with caregivers
and children experiencing parental (typically maternal) incarceration, in a
community setting. We partnered with a community-based organization serving
families with an incarcerated parent to conduct a pilot trial of the
Strengthening Families Program (SFP). Process evaluation indicated high
implementation fidelity, satisfaction, engagement, and attendance. Outcome
evaluation results indicated positive changes in family-level functioning,
caregivers' positive parenting, and caregiver depression symptoms from pre- to
post-intervention, with some changes retained at follow-up 4 months later.
Implications for preventive interventions with children of incarcerated parents,
and their caregivers, are discussed.
PMID- 24353365
TI - Gold(I) and Palladium(II) Complexes of 1,3,4-Trisubstituted 1,2,3-Triazol-5
ylidene "Click" Carbenes: Systematic Study of the Electronic and Steric Influence
on Catalytic Activity.
AB - The synthesis of a small family of six electronically and sterically modified
1,3,4-trisubstituted 1,2,3-triazol-5-ylidene gold(I) chloride complexes is
described. Additionally, the corresponding trans-[PdBr2(iPr2-bimy)(1,3,4
trisubstituted 1,2,3-triazol-5-ylidene)] complexes are also generated and used to
examine the donor strength of the 1,3,4-trisubstituted 1,2,3-triazol-5-ylidene
ligands. All compounds have been characterized by 1H and 13C NMR and IR
spectroscopy, high-resolution electrospray mass spectrometry (HR-ESI-MS), and
elemental analysis. The molecular structures of four of the gold(I) and four of
the palladium(II) complexes were determined using X-ray crystallography. Finally,
it is demonstrated that these 1,2,3-triazol-5-ylidene gold(I) chloride complexes
(Au(trz)Cl) are able to catalyze the cycloisomerization of 1,6-enynes, in high
yield and regioselectivity, as well as the intermolecular direct etherification
of allylic alcohols. Exploiting the Au(trz)Cl precatalysts allowed the
etherification of allylic alcohols to be carried out under milder conditions,
with better yield and regioselectivity than selected commercially available
gold(I) catalysts.
PMID- 24353368
TI - Development of a Family-School Intervention for Young Children With Attention
Deficit Hyperactivity Disorder.
AB - Although numerous studies have evaluated the effectiveness of multi-modal
psychosocial interventions for children with attention deficit hyperactivity
disorder, these programs are limited in that there has not beeti an explicit
focus on the connection between fatnily and school. This study was designed to
develop and pilot test a family-school ititervention, Family-School Success-Early
Elementary (FSS-EE), for kindergarten and first-grade studetits with attention
deficit hyperactivity disorder. Key components of FSS-EE were family-school
behavioral consultatioti, daily report cards, and strategies to improve parent
child relationships atid family involvement in educatioti. FSS-EE was developed
using a multistep iterative process. The piloted version consisted of 12 weekly
sessions including 6 group meetings, 4 individualized family sessions, and 2
school-based consultations. Families participating in the study were given the
choice of placing their childreti on medication; 25% of children were on
medication at the time of random assignmetit. Childreti (n = 61) were randomly
assigned to FSS-EE or a comparison group controlling for nonspecific treatment
effects. Outcomes were assessed at post interventioti and 2-month follow-up.
Study findings indicated that FSS-EE was feasible to implement and acceptable to
paretits atid teachers. In addition, the findings provided preliminary evidence
that FSS-EE is effective in improving parenting practices, child behavior at
school, and the student-teacher relationship.
PMID- 24353369
TI - On the Expected Values of Sequences of Functions.
AB - We prove new extensions to lemmas about combinations of convergent sequences of
distribution functions and absolutely continuous bounded functions. New lemma
one, a generalized Helly theorem, allows computing the limit of the expected
value of a sequence of functions with respect to a sequence of measures.
Previously published results allow either the function or the measure to be a
sequence, but not both. Lemma two allows computing the expected value of an
absolutely continuous monotone function by integrating the probabilities of the
inverse function values. Previous results were restricted to the identity
function. Lemma three gives a computationally and analytically convenient form
for the limit of the expected value of a sequence of functions of a sequence of
random variables. This is a new result that follows directly from the first two
lemmas. Although the lemmas resemble standard results and seem obviously true, we
have found only similar looking and related but quite distinct results in the
literature. We provide examples which highlight the value of the new results.
PMID- 24353370
TI - Simulator Study of Driver Responses to Pedestrian Treatments at Multilane
Roundabouts.
AB - Previous studies have shown that roundabouts - especially multilane roundabouts -
pose accessibility challenges to pedestrians with vision impairments, in part due
to a lack of yielding by drivers, especially on multilane roundabout exit legs.
In this study, three different treatments are assessed in terms of their
propensity for increasing driver yielding rate using a driving simulator. These
are stop bar and crosswalk relocation away from the beginning of exit leg, and
two types of beacons, namely a Pedestrian Hybrid Beacon (PHB) and a Rectangular
Rapid Flashing Beacon (RRFB). The study shows that installation of any kind of
beacon (PHB or RRFB) with or without crosswalk relocation increases driver
yielding rates significantly. Relocating the crosswalk does not provide a
significant increase in driver yielding rate for the base case, but appeared to
further enhance the effectiveness of the PHB and RRFB treatments. The results of
using an eye tracker on drivers to track their gaze pattern while exiting the
roundabout shows that having a beacon installed with crosswalk relocation
increases drivers' attention both on the beacon and the pedestrian along the
road. However, a portion of participants failed to see and react to the
pedestrian treatments, causing concern about the visibility of these treatments
at the roundabout exit leg.
PMID- 24353371
TI - Cognitive Processes in Response to Goal Failure: A Study of Ruminative Thought
and its Affective Consequences.
AB - Failure to make progress toward personal goals can lead to negative affective
states, such as depression and anxiety. Past research suggests that rumination in
response to goal failure may prolong and intensify those acute emotional
responses, but that process remains unclear. We examined ruminative thought
processes following experimentally manipulated exposure to past failures to
attain advancement (promotion) goals and safety (prevention) goals. We predicted
that priming of past promotion and prevention goal failures would lead
individuals to think repetitively about these failures and that negative affect
would be evoked by their recognition of their failures. Further, we predicted
that when people experience a sufficient magnitude of negative affect, ruminative
thought would intensify and prolong the negative affect associated with that type
of goal failure. Results yielded strong support for our predictions regarding
promotion goal failure and modest support for those regarding prevention goal
failure.
PMID- 24353372
TI - Sibling Caretaking Among Mexican American Youth: Conditions That Promote and
Hinder Personal and School Success.
AB - This study examined how Mexican American youths' extent of sibling caretaking is
related to their personal and school adjustment, and whether mothers' gender-role
attitudes and youths' familistic beliefs moderate these associations. One hundred
and ninety-five Mexican American youth (M age 14.8 years; 64% girls) and their
mothers participated in the study. Youth completed questionnaires about their
extent of sibling caretaking, their educational aspirations, school involvement,
school absences, grades, and their prosocial tendencies. Results indicated that,
when examined singly, frequent sibling caretaking was related to youths' higher
educational aspirations, greater prosocial tendencies, and more school engagement
for older youth, but also to more school absences. When extensive sibling care
was coupled with mothers' sex-stereotyped attitudes, youth experienced poorer
outcomes. Youth who held strong familistic beliefs and were highly involved in
sibling care reported lower educational aspirations, particularly girls. Findings
underscore the importance of considering socialization influences when evaluating
associations between sibling caretaking and youths' development.
PMID- 24353373
TI - Internal and environmental effects on folding and dimerization of the Alzheimer's
beta amyloid peptide.
AB - Amyloid deposits are a hallmark of many diseases. In the case of Alzheimer's
disease a turn between 21Ala and 30Ala, stabilized by a salt bridge between
22Glu/23Asp and 28Lys, may nucleate folding and aggregation of the Abeta peptide.
In the present paper we test this hypothesis by studying how salt bridge and turn
formation vary with intrinsic and environmental changes, and how these changes
effect folding and aggregation of the Abeta peptide.
PMID- 24353374
TI - On the dynamics of the age structure, dependency, and consumption.
AB - We examine the effects of population aging due to declining fertility and rising
elderly life expectancy on consumption possibilities in the presence of
intergenerational transfers. Our analysis is based on a highly tractable
continuous-time overlapping generations model in which the population is divided
into three groups (youth dependents, workers, and elderly dependents) and
lifecourse transitions take place in a probabilistic fashion. We show that the
consumption-maximizing response to greater longevity in highly developed
countries is an increase in fertility. However, with larger transfer payments,
the actual fertility response will likely be the opposite, leading to further
population aging.
PMID- 24353375
TI - Bayesian Hierarchical Semiparametric Modelling of Longitudinal Post-treatment
Outcomes from Open Enrolment Therapy Groups.
AB - There are several challenges to testing the effectiveness of group therapy-based
interventions in alcohol and other drug use (AOD) treatment settings. Enrollment
into AOD therapy groups typically occurs on an open (rolling) basis. Changes in
therapy group membership induce a complex correlation structure among client
outcomes, with relatively small numbers of clients attending each therapy group
session. Primary outcomes are measured post-treatment, so each datum reflects the
effect of all sessions attended by a client. The number of post-treatment
outcomes assessments is typically very limited. The first feature of our modeling
approach relaxes the assumption of independent random effects in the standard
multiple membership model by employing conditional autoregression (CAR) to model
correlation in random therapy group session effects associated with clients'
attendance of common group therapy sessions. A second feature specifies a
longitudinal growth model under which the posterior distribution of client
specific random effects, or growth parameters, is modeled non-parametrically. The
Dirichlet process prior helps to overcome limitations of standard parametric
growth models given limited numbers of longitudinal assessments. We motivate and
illustrate our approach with a data set from a study of group cognitive
behavioral therapy to reduce depressive symptoms among residential AOD treatment
clients.
PMID- 24353376
TI - Towards Analysis of Growth Trajectory through Multi-modal Longitudinal MR
Imaging.
AB - The human brain undergoes significant changes in the first few years after birth,
but knowledge about this critical period of development is quite limited.
Previous neuroimaging studies have been mostly focused on morphometric measures
such as volume and shape, although tissue property measures related to the degree
of myelination and axon density could also add valuable information to our
understanding of brain maturation. Our goal is to complement brain growth
analysis via morphometry with the study of longitudinal tissue property changes
as reflected in patterns observed in multi-modal structural MRI and DTI. Our
preliminary study includes eight healthy pediatric subjects with repeated scans
at the age of two weeks, one year, and two years with T1, T2, PD, and DT MRI.
Analysis is driven by the registration of multiple modalities and time points
within and between subjects into a common coordinate frame, followed by image
intensity normalization. Quantitative tractography with diffusion and structural
image parameters serves for multi-variate tissue analysis. Different patterns of
rapid changes were observed in the corpus callosum and the posterior and anterior
internal capsule, structures known for distinctly different myelination growth.
There are significant differences in central versus peripheral white matter, and
also a wm/gm contrast flip in both T1 and T2 images but not diffusion parameters.
We demonstrate that the combined longitudinal analysis of structural and
diffusion MRI proves superior to individual modalities and might provide a better
understanding of the trajectory of early neurodevelopment.
PMID- 24353377
TI - Evaluation of DTI Property Maps as Basis of DTI Atlas Building.
AB - Compared to region of interest based DTI analysis, voxel-based analysis gives
higher degree of localization and avoids the procedure of manual delineation with
the resulting intra and inter-rater variability. One of the major challenges in
voxel-wise DTI analysis is to get high quality voxel-level correspondence. For
that purpose, current DTI analysis tools are building on nonlinear registration
algorithms that deform individual datasets into a template image that is either
precomputed or computed as part of the analysis. A variety of matching criteria
and deformation schemes have been proposed, but often comparative evaluation is
missing. In our opinion, the use of consistent and unbiased measures to evaluate
current DTI procedures is of great importance and our work presents two possible
measures. Specifically, we propose the evaluation criteria generalization and
specificity, originally introduced by the shape modeling community, to evaluate
and compare different DTI nonlinear warping results. These measures are of
indirect nature and have a population wise view. Both measures incorporate
information of the variability of the registration results in the template space
via a voxel-wise PCA model. Thus far, we have used these measures to evaluate our
own DTI analysis procedure employing fluid-based registration on scalar DTI maps.
Generalization and specificity from tensor images in the template space were
computed for 8 scalar property maps. We found that for our procedure an intensity
normalized FA feature outperformed the other scalar measurements. Also, using the
tensor images rather than the FA maps as a comparison frame seemed to produce
more robust results.
PMID- 24353378
TI - Changes of MR and DTI appearance in early human brain development.
AB - Understanding myelination in early brain development is of clinical importance,
as many neurological disorders have their origin in early cerebral organization
and maturation. The goal of this work is to study a large neonate database
acquired with standard MR imagery to illuminate effects of early development in
MRI. 90 neonates were selected from a study of healthy brain development.
Subjects were imaged via MRI postnatally. MR acquisition included high-resolution
structural and diffusion tensor images. Unbiased atlases for structural and DTI
data were generated and co-registered into a single coordinate frame for voxel
wise comparison of MR and DTI appearance across time. All original datasets were
mapped into this frame and structural image data was additionally intensity
normalized. In addition, myelinated white matter probabilistic segmentations from
our neonate tissue segmentation were mapped into the same space to study how our
segmentation results were affected by the changing intensity characteristics in
early development Linear regression maps and p-value maps were computed and
visualized. The resulting visualization of voxels-wise corresponding maps of all
MR and DTI properties captures early development information in MR imagery.
Surprisingly, we encountered regions of seemingly decreased myelinated WM
probability over time even though we expected a confident increase for all of the
brain. The intensity changes in the MR images in those regions help explain this
counterintuitive result. The regressional results indicate that this is an effect
of intensity changes due not solely to myelination processes but also likely
brain dehydration processes in early postnatal development.
PMID- 24353379
TI - Quality Control of Diffusion Weighted Images.
AB - Diffusion Tensor Imaging (DTI) has become an important MRI procedure to
investigate the integrity of white matter in brain in vivo. DTI is estimated from
a series of acquired Diffusion Weighted Imaging (DWI) volumes. DWI data suffers
from inherent low SNR, overall long scanning time of multiple directional
encoding with correspondingly large risk to encounter several kinds of artifacts.
These artifacts can be too severe for a correct and stable estimation of the
diffusion tensor. Thus, a quality control (QC) procedure is absolutely necessary
for DTI studies. Currently, routine DTI QC procedures are conducted manually by
visually checking the DWI data set in a gradient by gradient and slice by slice
way. The results often suffer from low consistence across different data sets,
lack of agreement of different experts, and difficulty to judge motion artifacts
by qualitative inspection. Additionally considerable manpower is needed for this
step due to the large number of images to QC, which is common for group
comparison and longitudinal studies, especially with increasing number of
diffusion gradient directions. We present a framework for automatic DWI QC. We
developed a tool called DTIPrep which pipelines the QC steps with a detailed
protocoling and reporting facility. And it is fully open source. This
framework/tool has been successfully applied to several DTI studies with several
hundred DWIs in our lab as well as collaborating labs in Utah and Iowa. In our
studies, the tool provides a crucial piece for robust DTI analysis in brain white
matter study.
PMID- 24353380
TI - Feasibility demonstration of frequency domain terahertz imaging in breast cancer
margin determination.
AB - In breast conservation surgery, surgeons attempt to remove malignant tissue along
with a surrounding margin of healthy tissue. Subsequent pathological analysis
determines if those margins are clear of malignant tissue, a process that
typically requires at least one day. Only then can it be determined whether a
follow-up surgery is necessary. This possibility of re-excision is undesirable in
terms of reducing patient morbidity, emotional stress and healthcare. It has been
shown that terahertz (THz) images of breast specimens can accurately
differentiate between breast carcinoma, normal fibroglandular tissue, and adipose
tissue. That study employed the Time-Domain Spectroscopy (TDS) technique. We are
instead developing a new technique, Frequency-Domain Terahertz Imaging (FDTI). In
this joint project between UMass/Amherst and UMass Medical School/Worcester
(UMMS), we are investigating the feasibility of the FDTI technique for THz
reflection imaging of breast cancer margins. Our system, which produces
mechanically scanned images of size 2cm * 2cm, uses a THz gas laser. The system
is calibrated with mixtures of water and ethanol and reflection coefficients as
low as 1% have been measured. Images from phantoms and specimens cut from breast
cancer lumpectomies at UMMS will be presented. Finally, there will be a
discussion of a possible transition of this FDTI setup to a compact and
inexpensive CMOS THz camera for use in the operating room.
PMID- 24353381
TI - Measures for Validation of DTI Tractography.
AB - The evaluation of analysis methods for diffusion tensor imaging (DTI) remains
challenging due to the lack of gold standards and validation frameworks.
Significant work remains in developing metrics for comparing fiber bundles
generated from streamline tractography. We propose a set of volumetric and tract
oriented measures for evaluating tract differences. The different methods
developed for this assessment work are: an overlap measurement, a point cloud
distance and a quantification of the diffusion properties at similar locations
between fiber bundles. The application of the measures in this paper is a
comparison of atlas generated tractography to tractography generated in
individual images. For the validation we used a database of 37 subject DTIs, and
applied the measurements on five specific fiber bundles: uncinate, cingulum (left
and right for both bundles) and genu. Each measurments is interesting for
specific use: the overlap measure presents a simple and comprehensive metric but
is sensitive to partial voluming and does not give consistent values depending on
the bundle geometry. The point cloud distance associated with a quantile
interpretation of the distribution gives a good intuition of how close and
similar the bundles are. Finally, the functional difference is useful for a
comparison of the diffusion properties since it is the focus of many DTI analysis
to compare scalar invariants. The comparison demonstrated reasonable similarity
of results. The tract difference measures are also applicable to comparison of
tractography algorithms, quality control, reproducibility studies, and other
validation problems.
PMID- 24353382
TI - Automatic corpus callosum segmentation using a deformable active Fourier contour
model.
AB - The corpus callosum (CC) is a structure of interest in many neuroimaging studies
of neuro-developmental pathology such as autism. It plays an integral role in
relaying sensory, motor and cognitive information from homologous regions in both
hemispheres. We have developed a framework that allows automatic segmentation of
the corpus callosum and its lobar subdivisions. Our approach employs constrained
elastic deformation of flexible Fourier contour model, and is an extension of
Szekely's 2D Fourier descriptor based Active Shape Model. The shape and
appearance model, derived from a large mixed population of 150+ subjects, is
described with complex Fourier descriptors in a principal component shape space.
Using MNI space aligned T1w MRI data, the CC segmentation is initialized on the
mid-sagittal plane using the tissue segmentation. A multi-step optimization
strategy, with two constrained steps and a final unconstrained step, is then
applied. If needed, interactive segmentation can be performed via contour
repulsion points. Lobar connectivity based parcellation of the corpus callosum
can finally be computed via the use of a probabilistic CC subdivision model. Our
analysis framework has been integrated in an open-source, end-to-end application
called CCSeg both with a command line and Qt-based graphical user interface
(available on NITRC). A study has been performed to quantify the reliability of
the semi-automatic segmentation on a small pediatric dataset. Using 5 subjects
randomly segmented 3 times by two experts, the intra-class correlation
coefficient showed a superb reliability (0.99). CCSeg is currently applied to a
large longitudinal pediatric study of brain development in autism.
PMID- 24353383
TI - Monitoring the Remineralization of Early Simulated Lesions using a pH Cycling
Model with CP-OCT.
AB - If caries lesions are detected early enough they can be arrested by chemical
intervention and dietary changes without the need for chemical intervention.
Optical coherence tomography is ideally suited to monitor the changes that occur
in caries lesions as a result of nonsurgical intervention, since OCT can
nondestructively image the internal structure of the lesion. One of the most
important changes that occurs in a lesion is preferential deposition of mineral
in the outer surface zone. The deposition creates a highly mineralized and weakly
scattering surface zone that is clearly visible in OCT images. Since this zone is
near the highly reflective surface it is necessary to use cross-polarization OCT
imaging to resolve this zone. Several CP-OCT studies have been conducted
employing different remineralization models that produce lesions with varying
mineral gradients. Previous studies have also demonstrated that automated
algorithms can be used to assess the lesion depth and severity even with the
presence of the weakly reflective surface zone. In this study we investigated the
remineralization of lesions of varying severity using a pH cycling
remineralization model and the change of the lesion was monitored using CP-OCT.
Although the lesion depth and severity decreased after remineralization, there
was still incomplete remineralization of the body of the lesion.
PMID- 24353384
TI - Clinical Monitoring of Early Caries Lesions using Cross Polarization Optical
Coherence Tomography.
AB - New methods are needed for the nondestructive measurement of tooth
demineralization and remineralization and to monitor the progression of incipient
caries lesions (tooth decay) for effective nonsurgical intervention and to
evaluate the performance of anti-caries treatments such as chemical treatments or
laser irradiation. Studies have shown that optical coherence tomography (OCT) has
great potential to fulfill this role, since it can be used to measure the depth
and severity of early lesions with an axial resolution exceeding 10-MUm. It is
easy to apply in vivo and it can be used to image the convoluted topography of
tooth occlusal surfaces. In this paper we present early results from two clinical
studies underway to measure the effect of fluoride intervention on early lesions.
CP-OCT was used to monitor early lesions on enamel and root surfaces before and
after intervention with fluoride varnish. The lesion depth and internal structure
were resolved for all the lesions examined and some lesions had well defined
surface zones of lower reflectivity that may be indicative of arrested lesions.
Changes were also noted in the structure of some of the lesions after fluoride
intervention.
PMID- 24353385
TI - Multiphoton Imaging of Upconverting Lanthanide Nanoparticles in Three Dimensional
Models of Cancer.
AB - While upconverting lanthanide nanoparticles have numerous advantages over other
exogenous contrast agents used in scanned multiphoton imaging, their long
luminescence lifetimes cause images collected with non-descanned detection to be
greatly blurred. We demonstrate herein the use of Richardson-Lucy deconvolution
to deblur luminescence images obtained via multiphoton scanning microscopy.
Images were taken of three dimensional models of colon and ovarian cancer
following incubation with NaYF4:Yb,Er nanoparticles functionalized with an
antibody for EGFR and folic acid respectively. Following deconvolution, images
had a lateral resolution on par with the optimal performance of the imaging
system used, ~1.2 MUm, and an axial resolution of ~5 MUm. Due to the relatively
high multiphoton excitation efficiency of these nanoparticles, it is possible to
follow binding of individual particles in tissue. In addition, their extreme
photostability allows for prolonged imaging without significant loss in
luminescence signal. With these advantageous properties in mind, we also discuss
the potential application of upconverting lanthanide nanoparticles for tracking
of specific, cancer relevant receptors in tissue.
PMID- 24353386
TI - Quantitative analysis of an enlarged area Solid State X-ray Image Intensifier
(SSXII) detector based on Electron Multiplying Charge Coupled Device (EMCCD)
technology.
AB - Present day treatment for neurovascular pathological conditions involves the use
of devices with very small features such as stents, coils, and balloons; hence,
these interventional procedures demand high resolution x-ray imaging under
fluoroscopic conditions to provide the capability to guide the deployment of
these fine endovascular devices. To address this issue, a high resolution x-ray
detector based on EMCCD technology is being developed. The EMCCD field-of-view is
enlarged using a fiber-optic taper so that the detector features an effective
pixel size of 37 um giving it a Nyquist frequency of 13.5 lp/mm, which is
significantly higher than that of the state of the art Flat Panel Detectors
(FPD). Quantitative analysis of the detector, including gain calibration,
instrumentation noise equivalent exposure (INEE) and modulation transfer function
(MTF) determination, are presented in this work. The gain of the detector is a
function of the detector temperature; with the detector cooled to 5 degrees C,
the highest relative gain that could be achieved was calculated to be 116 times.
At this gain setting, the lowest INEE was measured to be 0.6 uR/frame. The MTF,
measured using the edge method, was over 2% up to 7 cycles/ mm. To evaluate the
performance of the detector under clinical conditions, an aneurysm model was
placed over an anthropomorphic head phantom and a coil was guided into the
aneurysm under fluoroscopic guidance using the detector. Image sequences from the
procedure are presented demonstrating the high resolution of this SSXII.
PMID- 24353387
TI - Intrinsic and total system performance evaluation for a newly developed Solid
State X-ray Image Intensifier (SSXII) detector.
AB - The new Solid State X-ray Image Intensifier (SSXII) is a high-resolution, high
sensitivity, real-time region-of-interest (ROI) x-ray imaging detector.
Evaluations were made of both standard linear systems metrics (MTF, DQE) and
total system performance with generalized linear systems metrics (GMTF, GDQE)
including scatter and geometric un-sharpness for simulated clinical conditions.
The SSXII is based on a 1k * 1k EMCCD sensor coupled to a 300 um thick CsI(Tl)
phosphor through a 2.88:1 fiber optic taper resulting in a 37 um effective pixel
size and an effective 3.7 cm * 3.7 cm square field-of-view (FOV). Standard
methods were used to calculate MTF, NNPS and DQE. Generalized metrics were
calculated and compared for three different magnifications (1.03, 1.11 and 1.2)
and three different focal spots (0.3 mm, 0.5 mm and 0.8 mm) for a scatter
fraction of 0.28. For an RQA5 spectrum, at 5 cycles/mm the MTF was found to be
0.06 and DQE was 0.04, while the DQE(0) was 0.60. Focal spot un-sharpness and
scatter significantly degrades the GMTF and GDQE performance of the detector. A
low frequency drop is caused by scatter and is almost independent of focal spot
size and magnification. The degradation for middle range frequencies is caused by
geometric un-sharpness and increases with focal spot size and magnification. This
degradation was least in the case of the small focal spot and almost independent
of magnification. In spite of this degradation, the high resolution SSXII with a
small FOV may have a significant impact on ROI image-guided neuro-interventions
since it demonstrates far better performance than standard current detectors.
PMID- 24353388
TI - Image acquisition, geometric correction and display of images from a 2*2 x-ray
detector array based on Electron Multiplying Charge Coupled Device (EMCCD)
technology.
AB - A high resolution (up to 11.2 lp/mm) x-ray detector with larger field of view
(8.5 cm * 8.5 cm) has been developed. The detector is a 2 * 2 array of individual
imaging modules based on EMCCD technology. Each module outputs a frame of size
1088 * 1037 pixels, each 12 bits. The frames from the 4 modules are acquired into
the processing computer using one of two techniques. The first uses 2 CameraLink
communication channels with each carrying information from two modules, the
second uses a application specific custom integrated circuits, the Multiple
Module Multiplexer Integrated Circuit (MMMIC), 3 of which are used to multiplex
the data from 4 modules into one CameraLink channel. Once the data is acquired
using either of the above mentioned techniques, it is decoded in the graphics
processing unit (GPU) to form one single frame of size 2176 * 2074 pixels each 16
bits. Each imaging module uses a fiber optic taper coupled to the EMCCD sensor.
To correct for mechanical misalignment between the sensors and the fiber optic
tapers and produce a single seamless image, the images in each module may be
rotated and translated slightly in the x-y plane with respect to each other. To
evaluate the detector acquisition and correction techniques, an aneurysm model
was placed over an anthropomorphic head phantom and a coil was guided into the
aneurysm under fluoroscopic guidance using the detector array. Image sequences
before and after correction are presented which show near-seamless boundary
matching and are well suited for fluoroscopic imaging.
PMID- 24353390
TI - Theoretical performance analysis for CMOS based high resolution detectors.
AB - High resolution imaging capabilities are essential for accurately guiding
successful endovascular interventional procedures. Present x-ray imaging
detectors are not always adequate due to their inherent limitations. The newly
developed high-resolution micro-angiographic fluoroscope (MAF-CCD) detector has
demonstrated excellent clinical image quality; however, further improvement in
performance and physical design may be possible using CMOS sensors. We have thus
calculated the theoretical performance of two proposed CMOS detectors which may
be used as a successor to the MAF. The proposed detectors have a 300 MUm thick HL
type CsI phosphor, a 50 MUm-pixel CMOS sensor with and without a variable gain
light image intensifier (LII), and are designated MAF-CMOS-LII and MAF-CMOS,
respectively. For the performance evaluation, linear cascade modeling was used.
The detector imaging chains were divided into individual stages characterized by
one of the basic processes (quantum gain, binomial selection, stochastic and
deterministic blurring, additive noise). Ranges of readout noise and exposure
were used to calculate the detectors' MTF and DQE. The MAF-CMOS showed slightly
better MTF than the MAF-CMOS-LII, but the MAF-CMOS-LII showed far better DQE,
especially for lower exposures. The proposed detectors can have improved MTF and
DQE compared with the present high resolution MAF detector. The performance of
the MAF-CMOS is excellent for the angiography exposure range; however it is
limited at fluoroscopic levels due to additive instrumentation noise. The MAF
CMOS-LII, having the advantage of the variable LII gain, can overcome the noise
limitation and hence may perform exceptionally for the full range of required
exposures; however, it is more complex and hence more expensive.
PMID- 24353389
TI - Design considerations for a new, high resolution Micro-Angiographic Fluoroscope
based on a CMOS sensor (MAF-CMOS).
AB - The detectors that are used for endovascular image-guided interventions (EIGI),
particularly for neurovascular interventions, do not provide clinicians with
adequate visualization to ensure the best possible treatment outcomes. Developing
an improved x-ray imaging detector requires the determination of estimated
clinical x-ray entrance exposures to the detector. The range of exposures to the
detector in clinical studies was found for the three modes of operation:
fluoroscopic mode, high frame-rate digital angiographic mode (HD fluoroscopic
mode), and DSA mode. Using these estimated detector exposure ranges and available
CMOS detector technical specifications, design requirements were developed to
pursue a quantum limited, high resolution, dynamic x-ray detector based on a CMOS
sensor with 50 MUm pixel size. For the proposed MAF-CMOS, the estimated charge
collected within the full exposure range was found to be within the estimated
full well capacity of the pixels. Expected instrumentation noise for the proposed
detector was estimated to be 50-1,300 electrons. Adding a gain stage such as a
light image intensifier would minimize the effect of the estimated
instrumentation noise on total image noise but may not be necessary to ensure
quantum limited detector operation at low exposure levels. A recursive temporal
filter may decrease the effective total noise by 2 to 3 times, allowing for the
improved signal to noise ratios at the lowest estimated exposures despite
consequent loss in temporal resolution. This work can serve as a guide for
further development of dynamic x-ray imaging prototypes or improvements for
existing dynamic x-ray imaging systems.
PMID- 24353391
TI - Effects of T2-Weighted MRI Based Cranial Volume Measurements on Studies of the
Aging Brain.
AB - Many brain aging studies use total intracranial volume (TIV) as a proxy measure
of premorbid brain size that is unaffected by neurodegeneration. T1-weighted
Magnetic Resonance Imaging (MRI) sequences are commonly used to measure TIV, but
T2-weighted MRI sequences provide superior contrast between the cerebrospinal
fluid (CSF) bounding the premorbid brain space and surrounding dura mater. In
this study, we compared T1-based and T2-based TIV measurements to assess the
practical impact of this superior contrast on studies of brain aging. 810
Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, including
healthy elders and those with mild cognitive impairment (MCI) and Alzheimer's
Disease (AD), received T1-weighted and T2-weighted MRI at their baseline
evaluation. TIV was automatically estimated from T1-weighted images using
FreeSurfer version 4.3 (T1TIV), and an automated active contour method was used
to estimate TIV from T2-weighted images (T2TIV). The correlation between T1TIV
and T2TIV was high (.93), and disagreement was greater on larger heads. However,
correcting a FreeSurfer-based measure of total parenchymal volume by dividing it
by T2TIV led to stronger expected associations with a standardized measure of
cognitive dysfunction (MMSE) in Poisson regression models among individuals with
AD (z=1.73 vs. 1.09) and MCI (z=3.15 vs. 2.79) than a corresponding parenchymal
volume measure divided by T1TIV. This effect was enhanced when the analysis was
restricted to the cases where T1TIV and T2TIV disagreed the most. These findings
suggest that T2-based TIV measurements may be higher fidelity than T1-based TIV
measurements, thus leading to greater sensitivity to detect biologically
plausible brain-behavior associations.
PMID- 24353392
TI - Fiber feature map based landmark initialization for highly deformable DTI
registration.
AB - This paper presents a novel pipeline for the registration of diffusion tensor
images (DTI) with large pathological variations to normal controls based on the
use of a novel feature map derived from white matter (WM) fiber tracts. The
research presented aims towards an atlas based DTI analysis of subjects with
considerable brain pathologies such as tumors or hydrocephalus. In this paper, we
propose a novel feature map that is robust against variations in WM fiber tract
integrity and use these feature maps to determine a landmark correspondence using
a 3D point correspondence algorithm. This correspondence drives a deformation
field computed using Gaussian radial basis functions(RBF). This field is employed
as an initialization to a standard deformable registration method like demons. We
present early preliminary results on the registration of a normal control dataset
to a dataset with abnormally enlarged lateral ventricles affected by fatal
demyelinating Krabbe disease. The results are analyzed based on a regional tensor
matching criterion and a visual assessment of overlap of major WM fiber tracts.
While further evaluation and improvements are necessary, the results presented in
this paper highlight the potential of our method in handling registration of
subjects with severe WM pathology.
PMID- 24353393
TI - Fully Automated Prostate Magnetic Resonance Imaging and Transrectal Ultrasound
Fusion via a Probabilistic Registration Metric.
AB - In this work, we present a novel, automated, registration method to fuse magnetic
resonance imaging (MRI) and transrectal ultrasound (TRUS) images of the prostate.
Our methodology consists of: (1) delineating the prostate on MRI, (2) building a
probabilistic model of prostate location on TRUS, and (3) aligning the MRI
prostate segmentation to the TRUS probabilistic model. TRUS-guided needle biopsy
is the current gold standard for prostate cancer (CaP) diagnosis. Up to 40% of
CaP lesions appear isoechoic on TRUS, hence TRUS-guided biopsy cannot reliably
target CaP lesions and is associated with a high false negative rate. MRI is
better able to distinguish CaP from benign prostatic tissue, but requires special
equipment and training. MRI-TRUS fusion, whereby MRI is acquired pre-operatively
and aligned to TRUS during the biopsy procedure, allows for information from both
modalities to be used to help guide the biopsy. The use of MRI and TRUS in
combination to guide biopsy at least doubles the yield of positive biopsies.
Previous work on MRI-TRUS fusion has involved aligning manually determined
fiducials or prostate surfaces to achieve image registration. The accuracy of
these methods is dependent on the reader's ability to determine fiducials or
prostate surfaces with minimal error, which is a difficult and time-consuming
task. Our novel, fully automated MRI-TRUS fusion method represents a significant
advance over the current state-of-the-art because it does not require manual
intervention after TRUS acquisition. All necessary preprocessing steps (i.e.
delineation of the prostate on MRI) can be performed offline prior to the biopsy
procedure. We evaluated our method on seven patient studies, with B-mode TRUS and
a 1.5 T surface coil MRI. Our method has a root mean square error (RMSE) for
expertly selected fiducials (consisting of the urethra, calcifications, and the
centroids of CaP nodules) of 3.39 +/- 0.85 mm.
PMID- 24353394
TI - Evaluation of embolic deflection device using optical particle tracking.
AB - Trans-aortic valve replacement is a new endovascular procedure which has started
to be used routinely in cardiac interventional suites. During such procedures a
stent-like device containing new aortic valves is placed over the damaged ones,
possibly causing calcifications to be dislodged and released in arteries leading
to stroke. To prevent such events, new devices are being developed to provide
distal protection to the brain supplying arteries. Currently there is a need to
evaluate such device efficacy in a repeatable manner. We are proposing and
investigating such a method based on particle optical tracking. We simulated such
protective devices using two porous screens (150 and 200 MUm pore size) which
were placed in an arterial bifurcation phantom connected to a clinically relevant
flow loop. A mask was acquired and gold embolic particles (100-300MUm) were
injected at a steady rate using a motorized injector. Optical images with 2 ms
exposure were acquired at 30 fps. Images were subtracted, thresholded and
filtered using a 5*5 median filter. ROI's were drawn over the main and
bifurcating arteries and a particle counting algorithm was used to estimate
particle flow rates in each artery for each run. The unprotected and the two
protected cases were evaluated. Before filter placement, the particle flow rate
was 60 and 40 %, respectively, of the main artery. After the filter placement,
the particle flow rate in the protected branch was 4% and 8% of the particle flow
rate in the main artery. We present a method to assess the efficacy of such
devices using an optical particle tracking and counting technique.
PMID- 24353395
TI - New silicon technologies enable high-performance arrays of Single Photon
Avalanche Diodes.
AB - In order to fulfill the requirements of many applications, we recently developed
a new technology aimed at combining the advantages of traditional thin and thick
silicon Single Photon Avalanche Diodes (SPAD). In particular we demonstrated
single-pixel detectors with a remarkable improvement in the Photon Detection
Efficiency at the longer wavelengths (e.g. 40% at 800nm) while maintaining a
timing jitter better than 100ps. In this paper we will analyze the factors the
currently prevent the fabrication of arrays of SPADs by adopting such a Red
Enhanced (RE) technology and we will propose further modifications to the device
structure that will enable the fabrication of high performance RE-SPAD arrays for
photon timing applications.
PMID- 24353396
TI - An Investigation of the Relations Between Student Knowledge, Personal Contact,
and Attitudes Toward Individuals with Schizophrenia.
AB - A survey of 118 MSW students was conducted to examine the relationship between
social work students' knowledge about, contact with, and attitudes toward persons
with schizophrenia. Hierarchical regression analyses indicated that students'
knowledge about and contact with persons with schizophrenia were significantly
related to better attitudes toward this population. Moderated multiple regression
analyses revealed a significant interaction between knowledge about and contact
with persons with schizophrenia, such that knowledge was only related to positive
attitudes among students who had more personal contact with persons with the
illness. Implications for social work training in severe mental illness are
discussed (99 words).
PMID- 24353397
TI - What Influences Social Workers' Attitudes Toward Working With Clients With Severe
Mental Illness?
AB - A national random survey of 2000 NASW members in post-master's practice in mental
health was conducted to investigate their experiences with and attitudes about
working with individuals with severe and persistent mental illness (SPMI).
Through a series of structural equation models, we examined the influence of
different frustrations reported by the respondents on their attitudes toward
working with individuals with SPMI. Results suggest that social workers'
attitudes toward working with individuals with SPMI are primarily influenced by
their frustrations related to client behaviors and treatment issues, rather than
frustrations with system related issues. Implications for social work practice
and directions for future research are discussed. (105 words).
PMID- 24353398
TI - The Context of Religious and Spiritual Care at the End of Life in Long-term Care
Facilities.
AB - Despite the increasing numbers of Americans who die in nursing homes (NHs) and
residential care/assisted living (RC/AL) facilities, and the importance of
religious and spiritual needs as one approaches death, little is known about how
these needs are met for dying individuals in long-term care (LTC) institutional
settings. This study compared receipt of religious and spiritual help in four
types of LTC settings: NHs, smaller (<16 beds) RC/AL facilities, traditional
RC/AL facilities, and new-model RC/AL facilities. Data were also available for
religious affiliation of the facilities, size, and provision of religious and
hospice services. Controlling for such factors, the importance of
religion/spirituality to the decedent was the strongest predictor of the
decedent's receipt of spiritual help. In addition, new-model RC/AL facilities
were significantly more likely to provide help for religious and spiritual needs
of decedent residents than other RC/AL types, but did not differ significantly
from NHs.
PMID- 24353399
TI - Response to Weidhaas and Slack re: Comments on "The role of KRAS rs61764370 in
invasive epithelial ovarian cancer: implication for clinical testing"
PMID- 24353400
TI - Letter to the editor: immediate implications of improved surgical efficiency.
PMID- 24353401
TI - Assessment of dry eye signs and symptoms and ocular tolerance of a preservative
free lacrimal substitute (Hylabak(r)) versus a preserved lacrimal substitute
(Systane(r)) used for 3 months in patients after LASIK.
AB - Laser-assisted in situ keratomileusis (LASIK) is commonly used to correct
refractive defects. The procedure frequently results in dry eye symptoms, usually
of short but sometimes longer duration. This study was designed to assess dry eye
and ocular tolerability after LASIK in patients treated with a preservative-free
lacrimal substitute (Hylabak(r)) or preserved lacrimal substitute (Systane(r)).
In a single-center, investigator-masked, prospective, noninferiority, clinical
study, patients undergoing LASIK surgery were randomized to receive Hylabak or
Systane eye drops (one drop in each eye four times daily for 3 months).
Fluorescein test scores were the primary efficacy variable and were similar on
day 1 (mean 0.26 and 0.28 for Hylabak and Systane, respectively). At the final
visit (day 84 +/- 3) the fluorescein scores had improved to 0.11 and 0.04,
respectively. The difference was not significant and thus noninferiority was
established. A trend of more rapid improvement in the Hylabak group was evident.
Both treatments were well tolerated and there were no serious adverse events,
discontinuations for adverse events or other safety-related reasons, and no
systemic adverse events. The results suggest that Hylabak is not less effective
than Systane in reducing the symptoms of dry eye after LASIK surgery.
PMID- 24353402
TI - Rapid growth of an orbital hemangiopericytoma with atypical histopathological
findings.
AB - Hemangiopericytoma is a rare vascular tumor that originates from pericytes. The
orbit is a rare location for this particular tumor, and corresponds to 0.8% to 3%
of all primary orbital tumors. We report a case of a hemangiopericytoma in a 45
year-old man that had an unusual presentation, as a rapidly growing mass in the
anterior right inferior orbit. Given that there are no clinical or radiological
signs pathognomonic of this tumor, a careful histopathological examination is
necessary to confirm the diagnosis. In our case, it presented also with unusual
histopathological findings. The clinical features, radiological findings,
differential diagnosis and treatment of this challenging entity are reviewed in
this case report.
PMID- 24353404
TI - Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis:
present, future, and insights into pathogenesis.
AB - The way rheumatoid arthritis is treated has changed dramatically with the
introduction of anti-tumor necrosis factor (anti-TNF) biologics. Nevertheless,
many patients still have less than adequate control of their disease activity
even with these therapeutic regimens, and current knowledge fails to explain all
the data already gathered. There is now a wide range of drugs from different
classes of biologic disease-modifying anti-rheumatic drugs available (and soon
this number will increase significantly), that provides the opportunity to
address each patient as a particular case and thereby optimize medical
intervention. Currently available biologics for the treatment of rheumatoid
arthritis apart from anti-TNF-based therapies are reviewed, along with an
analysis of the new insights they provide into the pathogenesis of the disease
and a discussion of future prospects in the area.
PMID- 24353406
TI - The influence of socioeconomic status on women's preferences for modern
contraceptive providers in Nigeria: a multilevel choice modeling.
AB - BACKGROUND: Contraceptives are one of the most cost effective public health
interventions. An understanding of the factors influencing users' preferences for
contraceptives sources, in addition to their preferred methods of contraception,
is an important factor in increasing contraceptive uptake. This study
investigates the effect of women's contextual and individual socioeconomic
positions on their preference for contraceptive sources among current users in
Nigeria. METHODS: A multilevel modeling analysis was conducted using the most
recent 2008 Nigerian Demographic and Health Surveys data of women aged between 15
and 49 years old. The analysis included 1,834 ever married women from 888
communities across the 36 states of the federation, including the Federal Capital
Territory of Abuja. Three outcome variables, private, public, and informal
provisions of contraceptive sources, were considered in the modeling. RESULTS:
There was variability in women's preferences for providers across communities.
The result shows that change in variance accounted for about 31% and 19% in the
odds of women's preferences for both private and public providers across
communities. Younger age and being from the richest households are strongly
associated with preference for both private and public providers. Living in rural
areas and economically deprived neighborhoods were the community level
determinants of women's preferences. CONCLUSION: This study documents the
independent association of contextual socioeconomic characteristics and
individual level socioeconomic factors with women's preferences for contraceptive
commodity providers in Nigeria. Initiatives that seek to improve modern
contraceptive uptake should jointly consider users' preferences for sources of
these commodities in addition to their preference for contraceptive type.
PMID- 24353405
TI - Disease-modifying drugs in Alzheimer's disease.
AB - Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the
most common cause of dementia. The early stages of AD are characterized by short
term memory loss. Once the disease progresses, patients experience difficulties
in sense of direction, oral communication, calculation, ability to learn, and
cognitive thinking. The median duration of the disease is 10 years. The pathology
is characterized by deposition of amyloid beta peptide (so-called senile plaques)
and tau protein in the form of neurofibrillary tangles. Currently, two classes of
drugs are licensed by the European Medicines Agency for the treatment of AD, ie,
acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N
methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment
with acetylcholinesterase inhibitors or memantine aims at slowing progression and
controlling symptoms, whereas drugs under development are intended to modify the
pathologic steps leading to AD. Herein, we review the clinical features,
pharmacologic properties, and cost-effectiveness of the available
acetylcholinesterase inhibitors and memantine, and focus on disease-modifying
drugs aiming to interfere with the amyloid beta peptide, including vaccination,
passive immunization, and tau deposition.
PMID- 24353407
TI - Electronically monitored medication adherence predicts hospitalization in heart
failure patients.
AB - BACKGROUND: Hospitalization contributes enormously to health care costs
associated with heart failure. Many investigators have attempted to predict
hospitalization in these patients. None of these models has been highly effective
in prediction, suggesting that important risk factors remain unidentified.
PURPOSE: To assess prospectively collected medication adherence, objectively
measured by the Medication Event Monitoring System, as a predictor of
hospitalization in heart failure patients. MATERIALS AND METHODS: We used
recently developed adaptive modeling methods to describe patterns of medication
adherence in a sample of heart failure patients, and tested the hypothesis that
poor medication adherence as determined by adaptive methods was a significant
predictor of hospitalization within 6 months. RESULTS: Medication adherence was
the best predictor of hospitalization. Besides two dimensions of poor adherence
(adherence pattern type and low percentage of prescribed doses taken), four other
single factors predicted hospitalization: low hemoglobin, depressed ejection
fraction, New York Heart Association class IV, and 12 or more medications taken
daily. Seven interactions increased the predictive capability of the model: 1)
pattern of poor adherence type and lower score on the Letter-Number Sequencing
test, a measure of short-term memory; 2) higher number of comorbid conditions and
higher number of daily medications; 3) higher blood urea nitrogen and lower
percentage of prescribed doses taken; 4) lower hemoglobin and much worse
perceived health compared to last year; 5) older age and lower score on the
Telephone Interview of Cognitive Status; 6) higher body mass index and lower
hemoglobin; and 7) lower ejection fraction and higher fatigue. Patients with none
of these seven interactions had a hospitalization rate of 9.7%. For those with
five of these interaction risk factors, 100% were hospitalized. The C-index (the
area under the receiver-operating characteristics [ROC] curve) for the model
based on the seven interactions was 0.83, indicating excellent discrimination.
CONCLUSION: Medication adherence adds important new information to the list of
variables previously shown to predict hospitalization in adults with heart
failure.
PMID- 24353409
TI - Managing hypercholesterolemia and preventing cardiovascular events in elderly and
younger Chinese adults: focus on rosuvastatin.
AB - Coronary heart disease (CHD) is the leading cause of death worldwide. The
efficacy and safety of statins in primary and secondary prevention of CHD is
confirmed in several large studies, and rosuvastatin is the latest statin on
market. We review the published literature on rosuvastatin in Chinese people. The
pharmacokinetics of rosuvastatin in Chinese is somewhat different from that in
Caucasians, but this does not influence the linear relationship between dosage
and efficacy and with no drug accumulation. Rosuvastatin 5-20 mg/day is effective
and safe in decreasing low-density lipoprotein cholesterol in both younger and
elderly patients with hypercholesterolemia, even in very elderly patients.
Rosuvastatin also shows anti-inflammatory and anti-atherosclerosis features, such
as reducing carotid intima-media thickness and plaque area. Rosuvastatin can also
improve the prognosis of Chinese CHD patients, such as in the case of acute
myocardial infarction. Its adverse-event rate is low and comparable to other
statins. In conclusion, rosuvastatin is effective and safe for younger or elderly
Chinese patients.
PMID- 24353408
TI - High-grade glioma in elderly patients: can the oncogeriatrician help?
AB - Gliomas are the most frequent primary brain tumors in adults. As the population
ages in Western countries, the number of people being diagnosed with glioblastoma
is expected to increase. Clinical management of elderly patients with primary
brain tumors is difficult, owing to multiple comorbidities, polypharmacy,
decreased tolerance to chemotherapy, and an increased risk of radiation-induced
neurotoxicity. A few specific randomized studies have shown a benefit for
radiotherapy in elderly patients with good performance status. For patients with
poor performance status, chemotherapy (temozolomide) has been shown to be
associated with prolonged duration of response. Patients with methylated O (6)
alkylguanine deoxyribonucleic acid alkyltransferase promoter seem to have better
outcomes. Oncogeriatrics proposes the geriatric evaluation of elderly patients to
improve therapeutic choices and optimize the management of treatment toxicities
and comorbidities.
PMID- 24353410
TI - Prevalence of dementia in Al-Quseir city, Red Sea Governorate, Egypt.
AB - Dementia is one of the most important public health problems as a result of the
rapid increase in the number of elderly persons worldwide. Improvement of
prevention strategies and caring for people with dementia should be undertaken.
We performed a door-to-door study to screen all subjects aged 50 years and older
(n=4,329 of 33,285 inhabitants) in Al-Quseir city. The screening was performed by
3 neuropsychiatrists, using a modified form of the Mini-Mental State Examination.
Suspected cases were subjected to case ascertainment according to Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnostic
criteria for dementia; full clinical assessment; psychometric assessment using
Cognitive Abilities Screening Instruments, Hachinski Ischaemic Score,
Instrumental Activities of Daily Living Scale and the Geriatric Depression Scale;
neuroimaging (computed tomography and/or magnetic resonance imaging); and
laboratory investigations for selected patients when indicated. The prevalence of
dementia was 2.01% for participants aged 50 years or older and 3.83% for those
aged 60 years or older. It increased steeply with increasing age to a maximum of
13.5% for those aged 80 years or older. Alzheimer's dementia (48.3%) was the most
common subtype, followed by vascular dementia (36.8%), dementia resulting from
general medical conditions (11.5%), and last, dementia resulting from multiple
etiologies (3.4%).
PMID- 24353411
TI - Indacaterol therapy in moderate-to-severe chronic obstructive pulmonary disease:
findings from a single-center primary care cohort.
AB - BACKGROUND: Once-daily long-acting beta2-agonists (LABAs) are an important
treatment option, either alone or in combination with other inhaled long-acting
bronchodilators in the management of chronic obstructive pulmonary disease
(COPD). AIMS/OBJECTIVES: To audit the effectiveness of indacaterol as maintenance
therapy in patients with moderate-to-severe COPD (Global initiative for chronic
Obstructive Lung Disease [GOLD] stage II/III). METHODS: This was a single-center
audit of a primary care COPD cohort comprising all patients treated with
indacaterol following treatment escalation (as per National Institute for Health
and Care Excellence guidelines) or failure with other therapies. The sample was
restricted to patients treated for a minimum of 12 months with indacaterol, for
whom preswitching and follow-up spirometry as well as exacerbation frequency data
were available (GOLD spirometry guidelines). Pulmonary function was assessed by
spirometry (recorded as forced expiratory volume in 1 second [FEV1] expressed as
percentage predicted). Relevant self-reported qualitative information was
recorded in descriptive terms for quality of life (QoL) assessment. RESULTS: A
total of 15 patients met the audit inclusion criteria (66.6% male, mean age
64.9+/-7.7 years). COPD disease duration ranged from 1 to 22 years; 93% had GOLD
stage II or III COPD. Follow-up ranged in duration from 12 to 27 months.
Indacaterol was associated with a significant reduction in exacerbation frequency
compared with the 12 months prior to initiation (P=0.02). In those patients who
experienced three or more exacerbations/year, mean exacerbation rate fell from
5.43+/-1.07 to 2.43+/-0.2 after 12 months treatment with indacaterol (P=0.02). A
reduction in dyspnea was noted in 53% of patients. Similarly, improvements in
exercise tolerance and well-being were self-reported in 67% and 93%,
respectively. CONCLUSION: Indacaterol was found to be an effective LABA as an
escalation or switch medication in patients with moderate-to-severe COPD.
Indacaterol was effective both as monotherapy and in combination with a long
acting muscarinic antagonist. Switching to indacaterol from a LABA/inhaled
corticosteroid fixed-combination inhaler significantly reduced the number of
acute exacerbations and also improved self-reported QoL.
PMID- 24353412
TI - Standardized evaluation of lung congestion during COPD exacerbation better
identifies patients at risk of dying.
AB - BACKGROUND: Congestive heart failure is underdiagnosed in patients with chronic
obstructive pulmonary disease (COPD). Pulmonary congestion on chest radiograph at
admission for acute exacerbation of COPD (AECOPD) is associated with an increased
risk of mortality. A standardized evaluation of chest radiographs may enhance
prognostic accuracy. PURPOSE: We aimed to evaluate whether a standardized,
liberal assessment of pulmonary congestion is superior to the routine assessment
in identifying patients at increased risk of long-term mortality, and to
investigate the association of heart failure with N-terminal prohormone of brain
natriuretic peptide (NT-proBNP) concentrations. MATERIAL AND METHODS: This was a
prospective cohort study of 99 patients admitted for AECOPD. Chest radiographs
obtained on admission were routinely evaluated and then later evaluated by
blinded investigators using a standardized protocol looking for Kerley B lines,
enlarged vessels in the lung apex, perihilar cuffing, peribronchial haze, and
interstitial or alveolar edema, defining the presence of pulmonary congestion.
Adjusted associations with long-term mortality and NT-proBNP concentration were
calculated. RESULTS: The standardized assessment was positive for pulmonary
congestion in 32 of the 195 radiographs (16%) ruled negative in the routine
assessment. The standardized assessment was superior in predicting death during a
median follow up of 1.9 years (P=0.022), and in multivariable analysis, only the
standardized assessment showed a significant association with mortality (hazard
ratio 2.4, 95% confidence interval [CI] 1.2-4.7) (P=0.016) and NT-proBNP
(relative concentration 1.8, CI 1.2-2.6) (P=0.003). CONCLUSION: By applying a
standardized approach when evaluating pulmonary congestion on chest radiographs
during AECOPD, a group of patients with increased risk of dying, possibly due to
heart failure, is identified.
PMID- 24353413
TI - Hospital readmissions following initiation of nebulized arformoterol tartrate or
nebulized short-acting beta-agonists among inpatients treated for COPD.
AB - BACKGROUND: Inpatient admissions for chronic obstructive pulmonary disease (COPD)
represent a significant economic burden, accounting for over half of direct
medical costs. Reducing 30-day readmissions could save health care resources
while improving patient care. Recently, the Patient Protection and Affordable
Care Act authorized reduced Medicare payments to hospitals with excess
readmissions for acute myocardial infarction, heart failure, and pneumonia.
Starting in October 2014, hospitals will also be penalized for excess COPD
readmissions. This retrospective database study investigated whether use of
arformoterol, a nebulized long-acting beta agonist, during an inpatient
admission, had different 30-day all-cause readmission rates compared with
treatment using nebulized short-acting beta agonists (SABAs, albuterol, or
levalbuterol). METHODS: A US nationally representative hospital database was used
to study adults aged >=40 years, discharged between January, 2006 and March,
2010, and with a diagnosis of COPD. Patients receiving arformoterol on >=80% of
days following treatment initiation were compared with patients receiving a
nebulized SABA during hospitalization. Arformoterol and nebulized SABA patients
were matched (1:2) for age, sex, severity of inpatient admission, and
primary/secondary COPD diagnosis. Logistic regression compared the odds of
readmission while adjusting for age, sex, race, admission type, severity,
primary/secondary diagnosis, other respiratory medication use, respiratory
therapy use, oxygen use, hospital size, and teaching status. RESULTS: This
retrospective study compared 812 arformoterol patients and 1,651 nebulized SABA
patients who were discharged from their initial COPD hospital admission. An
intensive care unit stay was more common among arformoterol patients (32.1%
versus 18.4%, P<0.001), suggesting more severe symptoms during the initial
admission. The observed readmission rate was significantly lower for arformoterol
patients than for nebulized SABA patients (8.7% versus 11.9%, P=0.017), as were
the adjusted odds of readmission (odds ratio 0.69, 95% confidence interval 0.51
0.92). CONCLUSION: All-cause 30-day readmission rates were significantly lower
for arformoterol patients than nebulized SABA patients, both before and after
adjusting for patient and hospital characteristics.
PMID- 24353414
TI - New developments in the management of COPD: clinical utility of indacaterol 75
MUg.
AB - Chronic obstructive pulmonary disease (COPD) is a global health challenge and a
major cause of mortality worldwide. Bronchodilators, particularly long-acting
beta2-agonists and long-acting antimuscarinic agents, used singly or in
combination, aim to improve lung function, reduce symptoms, prevent
exacerbations, and enhance quality of life of COPD patients. Indacaterol is a
novel, inhaled, long-acting beta2-agonist, with rapid onset of action and once
daily dosing providing 24-hour bronchodilation. Currently, the recommended dose
differs between Europe (150 MUg; maximum 300 MUg) and USA (75 MUg), the latter is
lower than that assessed in the majority of the conducted studies. This review
summarises published evidence regarding the efficacy, tolerability, and safety of
indacaterol at a dose of 75 MUg. Indacaterol 75 MUg was found to be superior than
placebo regarding lung function, dyspnea, health status, use of rescue
medication, and rate of exacerbations. Furthermore, indacaterol 75 MUg was well
tolerated, while the most frequent adverse effect was deterioration of COPD
occurring at a frequency similar to placebo, without major cardiovascular adverse
effects. In conclusion, indacaterol 75 MUg, administered once daily, is
efficacious and has an excellent tolerability and safety profile, and is
therefore a valid alternative in the treatment of COPD patients.
PMID- 24353415
TI - Tumor targeting and imaging with dual-peptide conjugated multifunctional
liposomal nanoparticles.
AB - BACKGROUND: The significant progress in nanotechnology provides a wide spectrum
of nanosized material for various applications, including tumor targeting and
molecular imaging. The aim of this study was to evaluate multifunctional
liposomal nanoparticles for targeting approaches and detection of tumors using
different imaging modalities. The concept of dual-targeting was tested in vitro
and in vivo using liposomes derivatized with an arginine-glycine-aspartic acid
(RGD) peptide binding to alphavbeta3 integrin receptors and a substance P peptide
binding to neurokinin-1 receptors. METHODS: For liposome preparation, lipids,
polyethylene glycol building blocks, DTPA-derivatized lipids for radiolabeling,
lipid-based RGD and substance P building blocks and imaging labels were combined
in defined molar ratios. Liposomes were characterized by photon correlation
spectroscopy and zeta potential measurements, and in vitro binding properties
were tested using fluorescence microscopy. Standardized protocols for
radiolabeling were developed to perform biodistribution and micro-single photon
emission computed tomography/computed tomography (SPECT/CT) studies in nude mice
bearing glioblastoma and/or melanoma tumor xenografts. Additionally, an initial
magnetic resonance imaging study was performed. RESULTS: Liposomes were
radiolabeled with high radiochemical yields. Fluorescence microscopy showed
specific cellular interactions with RGD-liposomes and substance P-liposomes.
Biodistribution and micro-SPECT/CT imaging of (111)In-labeled liposomal
nanoparticles revealed low tumor uptake, but in a preliminary magnetic resonance
imaging study with a single-targeted RGD-liposome, uptake in the tumor xenografts
could be visualized. CONCLUSION: The present study shows the potential of
liposomes as multifunctional targeted vehicles for imaging of tumors combining
radioactive, fluorescent, and magnetic resonance signaling. Specific in vitro
tumor targeting by fluorescence microscopy and radioactivity was achieved.
However, biodistribution studies in an animal tumor model revealed only moderate
tumor uptake and no additive effect using a dual-targeting approach.
PMID- 24353416
TI - Are calcifying microvesicles another analogous substructure of calcifying
nanoparticles?
PMID- 24353417
TI - Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded
solid lipid nanoparticles.
AB - The high aqueous solubility, poor permeability, and absorption of berberine (BBR)
result in its low plasma level after oral administration, which greatly limits
its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to
achieve improved bioavailability and prolonged effect. Developed SLNs showed
homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV),
encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray
diffraction combined with (1)H nuclear magnetic resonance spectroscopy was
employed to analyze chemical functional groups and the microstructure of BBR
SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50
mg/kg) oral pharmacokinetic studies in rats showed significant improvement
(P<0.05) in the peak plasma concentration, area under the curve, and variance of
mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting
improved bioavailability. Furthermore, oral administration of both BBR and BBR
SLNs significantly suppressed body weight gain, fasting blood glucose levels, and
homeostasis assessment of insulin resistance, and ameliorated impaired glucose
tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose
(100 mg/kg) showed more potent effects when compared to an equivalent dose of
BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet
function and protected the islet from regeneration. In conclusion, our study
demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti
diabetic action were effectively enhanced.
PMID- 24353420
TI - Sigma-1 receptor concentration in plasma of patients with late-life depression: a
preliminary study.
AB - BACKGROUND: Recently, the sigma-1 receptor has been shown to play a significant
role in the neural transmission of mood by regulating N-methyl-D-aspartate
receptors. Additionally, the sigma-1 receptor has been reported to influence
cognitive functions including learning and memory. In this study, we measured
plasma sigma-1 receptor concentrations before and after antidepressant treatment
in patients with late-life major depressive disorder (MDD) and explored whether
changes in depressive status are related to sigma-1 receptor concentrations.
METHODS: The study participants were 12 subjects with late-life MDD diagnosed
according to the criteria of the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition. All of the participants were over 60 years old.
Immediately prior to and 8 weeks after the start of treatment, sigma-1 receptor
concentration and mental status, including depressive symptoms (Hamilton
Depression Rating Scale; HAM-D), were measured. Treatment for depression was
performed according to a developed algorithm based on the choice of treatments.
We examined the association between changes in sigma-1 receptor concentration and
HAM-D scores during antidepressant treatment. For the measurement of plasma sigma
1 receptor concentration, blood plasma samples were separated by sodium dodecyl
sulfate polyacrylamide gel electrophoresis. Western blots were performed using a
specific antibody that acts against the sigma-1 receptor, and the net densities
of each band were quantified. RESULTS: All participants showed improvement in
depressive symptoms, which was indicated by a significant decrease in the HAM-D
scores. The mean plasma sigma-1 receptor concentration also increased
significantly following antidepressant treatment. However, no significant
correlations were found between changes in plasma sigma-1 receptor concentration
and changes in HAM-D scores. CONCLUSION: In this preliminary study, we
demonstrated that the sigma-1 receptor concentration in plasma increases
following antidepressant treatment in patients with late-life MDD. Further
studies are warranted to confirm this finding with a larger number of patients.
PMID- 24353421
TI - Randomized, placebo-controlled, double-blind study assessing the efficacy and
safety of paliperidone palmitate in Asian patients with schizophrenia.
AB - BACKGROUND: This 13-week, double-blind study was conducted to confirm the
efficacy and safety of paliperidone palmitate (PP), at dosing regimens approved
in other countries, in Asian patients with schizophrenia. METHODS: Asian patients
(aged >=20 years) diagnosed with schizophrenia (Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition-Text Revision criteria), and having a
Positive and Negative Syndrome Scale (PANSS) total score of 60 to 120 were
enrolled and randomized (1:1) to a PP or placebo group. Patients received PP
intramuscularly at recommended doses: initiation dose 150 mg equivalent (eq) PP
on day 1 and 100 mg eq PP on day 8 (deltoid); and a monthly maintenance dose of
75 mg eq PP on days 36 and 64 (deltoid or gluteal). The change from baseline to
week 13 in PANSS total scores (primary endpoint), Clinical Global Impression
Severity (CGI-S) scores, and PANSS Marder factor scores and subscales, and
responder rate at week 13 were evaluated. Safety was also assessed. RESULTS: The
PANSS total score (P<0.0001, least-squares mean change from baseline to week 13:
PP, -3.5; placebo, +6.2), CGI-S score (P<0.0001), and PANSS Marder factor scores
(P<=0.0025) were significantly improved at week 13 in the PP group versus
placebo. More treatment responders (>=30% decrease in PANSS total score) were in
the PP group (22.8%) versus placebo (8.5%). Insomnia (PP 17.0% versus placebo
15.2%), injection site pain (13.2% versus 6.7%), nasopharyngitis (12.6% versus
6.1%), psychiatric symptoms (11.3% versus 26.2%), and extrapyramidal symptoms
(10.1% versus 4.9%) were the most frequently occurring treatment-emergent adverse
events. CONCLUSION: PP is efficacious for Asian patients with schizophrenia at
the dosing regimen approved in other countries, with a similar safety and
tolerability profile.
PMID- 24353422
TI - Salivary alpha-amylase and cortisol responsiveness following electrically
stimulated physical stress in bipolar disorder patients.
AB - BACKGROUND: Bipolar disorder (BP) is often associated with a change in
hypothalamus- pituitary-adrenal axis function change due to chronic stress.
Salivary alpha-amylase (sAA) levels increase in response to psychosocial stress
and thus function as a marker of sympathoadrenal medullary system activity.
However, sAA has been studied less often than salivary cortisol in BP patients.
METHOD: We measured Profile of Mood States and State-Trait Anxiety Inventory
scores, heart rate variability, and salivary cortisol levels during electrical
stimulation stress in 25 BP patients and 22 healthy volunteers. RESULTS: Tension
anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores in
BP patients significantly increased compared with those of the healthy controls.
In contrast, the vigor scores of BP patients significantly decreased compared
with those of the healthy controls. Significant difference in the sAA levels was
observed between BP patients and healthy controls. sAA of female patients was
significantly higher than that of female healthy controls, and sAA in male
patients tended to be higher than that of male healthy controls. No difference in
salivary cortisol was observed between BP patients and the healthy controls. Only
three time points were measured before and after the electrical stimulation
stress. Furthermore, sAA secretion by BP patients increased before and after
electrical stimulation. CONCLUSION: These preliminary results suggest that sAA
may be a useful biological marker for BP patients.
PMID- 24353424
TI - Navigated transcranial magnetic stimulation in preoperative planning for the
treatment of motor area cavernous angiomas.
AB - Since the introduction of microscopic techniques, radical surgery for cavernous
angiomas has become a recommended treatment option. However, the treatment of
motor area cavernous angioma represents a great challenge for the surgical team.
Here, we describe an approach guided by frameless neuronavigation and
preoperative functional mapping with transcranial magnetic stimulation (TMS), for
surgical planning. We used TMS to map the motor cortex and its relationship with
the angioma. We achieved complete resection of the lesions in the surgeries,
while avoiding areas of motor response identified during the preoperative
mapping. We verified the complete control of seizures (Engel class 1A) in the
patients with previous refractory epilepsy. Postsurgery, one patient was seizure
free without medication, and two patients required only one medication for
seizure control. Thus, navigated TMS appears to be a useful tool, in preoperative
planning for cavernous angiomas of the motor area.
PMID- 24353425
TI - Sampling times and genotyping concerns in bioequivalence evaluation of branded
and generic formulations.
PMID- 24353423
TI - 22q11 deletion syndrome: a review of the neuropsychiatric features and their
neurobiological basis.
AB - The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant
microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is
among the most clinically variable syndromes, with more than 180 features related
with the deletion, and is associated with an increased risk of psychiatric
disorders, accounting for up to 1%-2% of schizophrenia cases. In recent years,
several genes located on chromosome 22q11 have been linked to schizophrenia,
including those encoding catechol-O-methyltransferase and proline dehydrogenase,
and the interaction between these and other candidate genes in the deleted region
is an important area of research. It has been suggested that haploinsufficiency
of some genes within the 22q11.2 region may contribute to the characteristic
psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an
extensive literature on neuroimaging shows reductions of the volumes of both gray
and white matter, and these findings suggest that this reduction may be
predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients.
Experimental and standardized cognitive assessments alongside neuroimaging may be
important to identify one or more endophenotypes of schizophrenia, as well as a
predictive prodrome that can be preventively treated during childhood and
adolescence. In this review, we summarize recent data about the 22q11DS, in
particular those addressing the neuropsychiatric and cognitive phenotypes
associated with the deletion, underlining the recent advances in the studies
about the genetic architecture of the syndrome.
PMID- 24353426
TI - Gabapentin enacarbil extended release for the treatment of postherpetic neuralgia
in adults.
AB - The development of biomedical technology is allowing refinement of drug therapies
in order to improve medication profiles and benefit patients. Gabapentin (Gp) is
a medication licensed globally for various indications, including postherpetic
neuralgia. It has a pharmacokinetic profile which has been suggested may limit
its clinical effects and reduce medication compliance. In 2012, the US Food and
Drug Administration licensed a novel preparation which aims to circumvent these
limitations. Gp enacarbil is a prodrug of Gp, which is additionally prepared in
an extended release preparation. The resulting compound has an improved
absorption profile and a reduced dosing frequency in comparison to immediate
release Gp. An absence of comparative data, however, limits the direct evaluation
of the medication to both immediate release and other extended release
preparations available on the market. Additionally, no data are currently
available addressing efficacy, tolerability, or side effects with other first
line treatments of postherpetic neuralgia. Additional experimental data should be
sought to clarify the position of Gp enacarbil, both within postherpetic
neuralgia treatment protocols and in relation to the increasing numbers of
gabapentinoids available.
PMID- 24353427
TI - Treatment of bisphosphonate related osteonecrosis following root canal therapy at
the 1-year follow-up: report of two cases.
AB - The objective of this report was to use topical gaseous ozone as an adjunct to
conventional treatment methods and to describe the multidisciplinary management
of bisphosphonate associated bone necrosis, which developed following endodontic
treatment. No complaints were noted by the patients at their 1-year follow-up and
the treatment showed favorable prognosis.
PMID- 24353428
TI - National Drug Formulary review of statin therapeutic group using the
multiattribute scoring tool.
AB - PURPOSE: HMG-CoA reductase inhibitors (statins) are extensively used in treating
hypercholesterolemia. The statins available in Malaysia include atorvastatin,
lovastatin, pravastatin, rosuvastatin, simvastatin, and fluvastatin. Over the
years, they have accumulated in the National Drug Formulary; hence, the need for
review. Effective selection of the best drugs to remain in the formulary can
become complex due to the multiple drug attributes involved, and is made worse by
the limited time and resources available. The multiattribute scoring tool (MAST)
systematizes the evaluation of the drug attributes to facilitate the drug
selection process. In this study, a MAST framework was developed to rank the
statins based on their utilities or benefits. METHODS: Published literature on
multicriteria decision analysis (MCDA) were studied and five sessions of expert
group discussions were conducted to build the MAST framework and to review the
evidence. The attributes identified and selected for analysis were efficacy
(clinical efficacy, clinical endpoints), safety (drug interactions, serious side
effects and documentation), drug applicability (drug strength/formulation,
indications, dose frequency, side effects, food-drug interactions, and dose
adjustments), and cost. The average weights assigned by the members for efficacy,
safety, drug applicability and cost were 32.6%, 26.2%, 24.1%, and 17.1%,
respectively. The utility values of the attributes were scored based on the
published evidence or/and agreements during the group discussions. The attribute
scores were added up to provide the total utility score. RESULTS: Using the MAST,
the six statins under review were successfully scored and ranked. Atorvastatin
scored the highest total utility score (TUS) of 84.48, followed by simvastatin
(83.11). Atorvastatin and simvastatin scored consistently high, even before drug
costs were included. The low scores on the side effects for atorvastatin were
compensated for by the higher scores on the clinical endpoints resulting in a
higher TUS for atorvastatin. Fluvastatin recorded the lowest TUS. CONCLUSION: The
multiattribute scoring tool was successfully applied to organize decision
variables in reviewing statins for the formulary. Based on the TUS, atorvastatin
is recommended to remain in the formulary and be considered as first-line in the
treatment of hypercholesterolemia.
PMID- 24353429
TI - Colchicine intoxication: a report of two suicide cases.
AB - Colchicine, an old and well-known drug, is an alkaloid extracted from Colchicum
autumnale and related species. Colchicine inhibits the deposition of uric acid
crystals and is an inhibitor of mitosis. Nausea, vomiting, abdominal pain, and
diarrhea, with a massive loss of fluid and electrolytes are the first clinical
symptoms of colchicine poisoning. Stomach lavage and rapid gastric
decontamination with activated charcoal are crucial. An acute dose of about 0.8
mg/kg of colchicine is presumed to be fatal. We report the clinical outcomes of
two different cases of colchicine intoxication for attempted suicide. The dose
required for morbidity or mortality varies significantly. The dose of 1 mg/kg in
the first case was directly related with mortality, while the dose of 0.2 mg/kg
in the second was related with survival. The other difference between the
patients was the time of arrival to hospital after ingestion. This period was 4
hours for case 1 and only 1, hour for case 2. The initiation of treatment later
than 2 hours after ingestion of colchicine may significantly impair treatment
because the absorption time for colchicine after oral administration is about 30
120 minutes. The rising lactate level and high anion gap metabolic acidosis in
our patient (case 1) were attributed to lactic acidosis, so hemodialysis was
performed, and the duration of hemodialysis was prolonged. Lactic acidosis in the
first case was one of the reasons for mortality. The most important parameters
which define the chance of survival are the dose of ingested drugs and the
arrival time to hospital after ingestion. The patients must be monitored closely
for lactic acidosis and the decision to start hemodialysis must be made promptly
for patients who develop lactic acidosis.
PMID- 24353430
TI - Analysis of US Food and Drug Administration Warning Letters: False Promotional
Claims Relating to Prescription and Over-the-Counter Medications.
AB - BACKGROUND: Recent studies have suggested that there has been an increase in the
number of 'warning letters' issued by the US Food and Drug Administration (FDA)
despite the publication of the FDA advertising guidelines. However, limited
information is available on the description of warning letters. The objective of
this study was to analyse the frequency and content of FDA warning letters in
relation to promotional claims and discuss the influence of regulatory and
industry constraints on promotion. METHODS: All warning letters published by the
FDA between 5 May 1995 and 11 June 2007 were reviewed. Warning letters related to
promotional issues were included and analysed. Information related to the
identification number, date of the warning letter, FDA division that issued the
letter, drug name, manufacturer, specific warning problem, type of promotional
material and requested action was extracted. Two independent investigators
reviewed and classified each PDF file, any differences were discussed until a
consensus was reached. RESULTS: Between May 1995 and June 2007 a total of 8692
warning letters were issued, of which 25% were related to drugs. Of these, 206
warning letters focused on drug promotion and were included in this study: 23%
were issued in 2005, 15% in 2004 and 14% in 1998. In total, 47% of the warning
letters were issued because of false or misleading unapproved doses and uses, 27%
failed to disclose risks, 15% cited misleading promotion, 8% related to
misleading labelling and 3% promoted false effectiveness claims. DISCUSSION:
There is an important variation in the number of warning letters issued in the
last decade, probably because of the increasing number of drugs approved by the
FDA, drug withdrawal scandals, and the publication of the FDA and the
Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines.
CONCLUSION: We found that benefit-related claims, such as unapproved uses or
doses of drugs, and failure to disclose risks, are the main causes of FDA issued
warning letters for promotional claims related to medications.
PMID- 24353431
TI - Chemotherapy and EGFR tyrosine kinase inhibitors for treatment of brain
metastases from non-small-cell lung cancer: survival analysis in 210 patients.
AB - BACKGROUND: Chemotherapy and epidermal growth factor receptor (EGFR) tyrosine
kinase inhibitors are controversial in the treatment of patients with brain
metastases from non-small-cell lung cancer (NSCLC). METHODS: We retrospectively
studied the effects of solely localized treatment or localized treatment in
combination with chemotherapy and/or EGFR tyrosine kinase inhibitors on outcomes
in 210 NSCLC patients with brain metastases. The effects of treatment modality,
Karnofsky performance status, age, primary tumor histology, number of brain
metastases, and other factors on survival time were analyzed, and the robustness
of two prognostic indices, ie, recursive partitioning analysis and graded
prognostic assessment, was evaluated. RESULTS: The median survival time in
patients with systemic medication and localized treatments was higher than in
those with localized treatments alone (11 versus 3 months, P=0.000). Within the
systemic medication group, median survival time was significantly longer for EGFR
tyrosine kinase inhibitors than for other types of chemotherapy (12 versus 9
months, P=0.002). In the EGFR tyrosine kinase inhibitor group, median survival
time for patients with EGFR gene mutation was 20 months versus 8 months for those
with the wild-type EGFR gene. The median survival time with pemetrexed was
significantly higher than with other chemotherapies (13 versus 7 months,
P=0.006). In multivariate analysis, the prognosis was significantly correlated
with treatment modality (P=0.000), Karnofsky performance status (P=0.000), number
of brain metastases (P=0.001), and histologic tumor type (P=0.007). In the graded
prognostic assessment model, survival curves for the subgroups showed clear
separations. CONCLUSION: NSCLC patients with brain metastasis benefited from
pemetrexed and/or tyrosine kinase inhibitors along with localized treatments, and
the graded prognostic assessment index is a robust model for prognostic
evaluation.
PMID- 24353432
TI - 5-grass pollen tablets achieve disease control in patients with seasonal allergic
rhinitis unresponsive to drugs: a real-life study.
AB - BACKGROUND: An important subpopulation in allergic rhinitis is represented by
patients with severe form of disease that is not responsive to drug treatment. It
has been reported that grass pollen subcutaneous immunotherapy is effective in
drug-resistant patients. In a real-life study, we evaluated the efficacy of 5
grass pollen tablets in patients with grass pollen-induced allergic rhinitis not
responsive to drug therapy. METHODS: We carried out this multicenter
observational study in adults and adolescents with grass-induced allergic
rhinitis not responsive to drug therapy who were treated for a year with 5-grass
pollen tablets. Clinical data collected before and after sublingual immunotherapy
(SLIT) included Allergic Rhinitis and its Impact on Asthma (ARIA) classification
of allergic rhinitis, response to therapy, and patient satisfaction. RESULTS:
Forty-seven patients entered the study. By ARIA classification, three patients
had moderate to severe intermittent allergic rhinitis, ten had mild persistent
allergic rhinitis, and 34 had moderate to severe persistent allergic rhinitis.
There were no cases of mild intermittent allergic rhinitis before SLIT. After
SLIT, 33 patients had mild intermittent allergic rhinitis, none had moderate to
severe intermittent allergic rhinitis, seven had mild persistent allergic
rhinitis, and seven had moderate to severe persistent allergic rhinitis. The mean
medication score decreased from 4.2+/-1.3 before to 2.4+/-2.0 after SLIT
(P<0.01), representing a reduction of 42%. The response to treatment before SLIT
was judged as poor by 70% of patients and very poor by 30%. Patient satisfaction
was significantly increased after SLIT (P<0.01). CONCLUSION: In real life, most
patients with grass pollen-induced allergic rhinitis not responsive to drug
treatment can achieve control of the condition with one season of treatment using
5-grass pollen tablets.
PMID- 24353433
TI - Limiting and controlling carbapenem-resistant Klebsiella pneumoniae.
AB - Carbapenem-resistant Klebsiella pneumoniae (CRKP) is resistant to almost all
antimicrobial agents, is associated with substantial morbidity and mortality, and
poses a serious threat to public health. The ongoing worldwide spread of this
pathogen emphasizes the need for immediate intervention. This article reviews the
global spread and risk factors for CRKP colonization/infection, and provides an
overview of the strategy to combat CRKP dissemination.
PMID- 24353434
TI - Investigation of age-related decline of microfibril-associated glycoprotein-1 in
human skin through immunohistochemistry study.
AB - During aging, the reduction of elastic and collagen fibers in dermis can lead to
skin atrophy, fragility, and aged appearance, such as increased facial wrinkling
and sagging. Microfibril-associated glycoprotein-1 (MAGP-1) is an extracellular
matrix protein critical for elastic fiber assembly. It integrates and stabilizes
the microfibril and elastin matrix network that helps the skin to endure
mechanical stretch and recoil. However, the observation of MAGP-1 during skin
aging and its function in the dermis has not been established. To better
understand age-related changes in the dermis, we investigated MAGP-1 during skin
aging and photoaging, using a combination of in vitro and in vivo studies. Gene
expression by microarray was performed using human skin biopsies from young and
aged female donors. In addition, immunofluorescence analysis on the MAGP-1
protein was performed in dermal fibroblast cultures and in human skin biopsies.
Specific antibodies against MAGP-1 and fibrillin-1 were used to examine protein
expression and extracellular matrix structure in the dermis via biopsies from
donors of multiple age groups. A reduction of the MAGP-1 gene and protein levels
were observed in human skin with increasing age and photoexposure, indicating a
loss of the functional MAGP-1 fiber network and a lack of structural support in
the dermis. Loss of MAGP-1 around the hair follicle/pore areas was also observed,
suggesting a possible correlation between MAGP-1 loss and enlarged pores in aged
skin. Our findings demonstrate that a critical "pre-elasticity" component, MAGP
1, declines with aging and photoaging. Such changes may contribute to age-related
loss of dermal integrity and perifollicular structural support, which may lead to
skin fragility, sagging, and enlarged pores.
PMID- 24353435
TI - Does tight glycemic control improve outcomes in pediatric patients undergoing
surgery and/or those with critical illness?
AB - This literature review examines the current evidence regarding the potential
usefulness of tight glycemic control in pediatric surgical patients. In adults,
fluctuations in glucose levels and/or prolonged hyperglycemia have been shown to
be associated with poor outcomes with respect to morbidity and mortality. This
review begins by summarizing the findings of key papers in adult patients and
continues by investigating whether or not similar results have been seen in
pediatric patients by performing a comprehensive literature review using Medline
(OVID). A database search using the OVID interface and including the search terms
(exp glucose) AND (exp surgery) AND (exp Paediatric/pediatric) AND (exp
Hypoglycaemia/hypoglycemia) AND (exp Hyperglycaemia/hyperglycemia) yielded a
total of 150+ papers, of which 24 fulfilled our criteria. We isolated papers
utilizing pediatric patients who were hospitalized due to illness and/or surgery.
Our review highlights several difficulties encountered in addressing this
potentially useful clinical intervention. An absence of scientifically robust and
randomized trials and the existence of several small-powered trials yielding
conflicting results mean we cannot recommend tight glycemic control in these
patients. Differences in study design and disagreements concerning the crucial
stage of surgery where hyperglycemia becomes important are compounded by an over
reliance on the discretion of clinicians in the absence of well described
treatment protocols. Closer inspection of key papers in adult patients identified
fundamental discrepancies between exact definitions of both hyperglycemia and
hypoglycemia. This lack of consensus, along with a fear of inducing iatrogenic
hypoglycemia in pediatric patients, has resulted in professional bodies advising
against this form of intervention. In conclusion, we cannot recommend use of
tight glycemic control in pediatric surgical patients due to unclear glucose
definitions, unclear thresholds for treatment, and the unknown long-term effects
of iatrogenic hypoglycemia on the developing body and brain.
PMID- 24353436
TI - Accuracy of diagnoses predicted from a simple patient questionnaire stratified by
the duration of general ambulatory training: an observational study.
AB - PURPOSE: To compare the diagnostic accuracy of diseases predicted from patient
responses to a simple questionnaire completed prior to examination by doctors
with different levels of ambulatory training in general medicine. PARTICIPANTS
AND METHODS: Before patient examination, five trained physicians, four short-term
trained residents, and four untrained residents examined patient responses to a
simple questionnaire and then indicated, in rank order according to their
subjective confidence level, the diseases they predicted. Final diagnosis was
subsequently determined from hospital records by mentor physicians 3 months after
the first patient visit. Predicted diseases and final diagnoses were codified
using the International Classification of Diseases version 10. A "correct"
diagnosis was one where the predicted disease matched the final diagnosis code.
RESULTS: A total of 148 patient questionnaires were evaluated. The Herfindahl
index was 0.024, indicating a high degree of diversity in final diagnoses. The
proportion of correct diagnoses was high in the trained group (96 of 148, 65%;
residual analysis, 4.4) and low in the untrained group (56 of 148, 38%; residual
analysis, -3.6) (chi (2)=22.27, P<0.001). In cases of correct diagnosis, the
cumulative number of correct diagnoses showed almost no improvement, even when
doctors in the three groups predicted >=4 diseases. CONCLUSION: Doctors who
completed ambulatory training in general medicine while treating a diverse range
of diseases accurately predicted diagnosis in 65% of cases from limited written
information provided by a simple patient questionnaire, which proved useful for
diagnosis. The study also suggests that up to three differential diagnoses are
appropriate for diagnostic prediction, while >=4 differential diagnoses barely
improved the diagnostic accuracy, regardless of doctors' competence in general
medicine. If doctors can become able to predict the final diagnosis from limited
information, the correct diagnostic outcome may improve and save further
consultation hours.
PMID- 24353437
TI - An unusual case of malignancy-related hypercalcemia.
AB - OBJECTIVE: To report the case of a 28-year-old woman who presented with
hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH)
24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm *
57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type)
pancreatic mass with liver metastases. INVESTIGATIONS AND TREATMENT:
Hypercalcemia was acutely managed with intravenous fluids, pamidronate and
calcitonin. Investigations for multiple endocrine neoplasia type 1 and
parathyroid adenoma were initiated. The identified neuroendocrine tumor was
treated with cisplatinum/etoposide chemotherapy. RESULTS: The pancreatic mass (56
mm * 49 mm) and metastases decreased in size with chemotherapy and calcium levels
normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased
to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm * 58 mm. The
patient was given a trial of cinacalcet but was unable to tolerate it.
Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49
mm * 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34
mmol/L). CONCLUSION: Ectopic PTH secreting tumors should be considered when there
is no parathyroid related cause for an elevated PTH. Recognizing the association
between PTH and hypercalcemia of malignancy may lead to an earlier detection of
an undiagnosed malignancy.
PMID- 24353439
TI - A practical and ethical solution to the opioid scheduling conundrum.
PMID- 24353438
TI - Mitigating the risk of opioid abuse through a balanced undergraduate pain
medicine curriculum.
AB - Chronic pain is highly prevalent in the United States and Canada, occurring in an
estimated 30% of the adult population. Despite its high prevalence, US and
Canadian medical schools provide very little training in pain management,
including training in the safe and effective use of potent analgesics, most
notably opioids. In 2005, the International Association for the Study of Pain
published recommendations for a core undergraduate pain management curriculum,
and several universities have implemented pilot programs based on this
curriculum. However, when outcomes have been formally assessed, these initiatives
have resulted in only modest improvements in physician knowledge about chronic
pain and its treatment. This article discusses strategies to improve
undergraduate pain management curricula and proposes areas in which those efforts
can be augmented. Emphasis is placed on opioids, which have great potency as
analgesics but also substantial risks in terms of adverse events and the risk of
abuse and addiction. The authors conclude that the most important element of an
undergraduate pain curriculum is clinical experience under mentors who are
capable of reinforcing didactic learning by modeling best practices.
PMID- 24353440
TI - Daily baseline skin care in the prevention, treatment, and supportive care of
skin toxicity in oncology patients: recommendations from a multinational expert
panel.
AB - Skin reactions due to radiotherapy and chemotherapy are a significant problem for
an important number of cancer patients. While effective for treating cancer, they
disturb cutaneous barrier function, causing a reaction soon after initiation of
treatment that impacts patient quality of life. Managing these symptoms with
cosmetics and nonpharmaceutical skin care products for camouflage or personal
hygiene may be important for increasing patient self-esteem. However,
inappropriate product choice or use could worsen side effects. Although
recommendations exist for the pharmaceutical treatment of skin reactions, there
are no recommendations for the choice or use of dermatologic skin care products
for oncology patients. The present guidelines were developed by a board of
European experts in dermatology and oncology to provide cancer care professionals
with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin
care management of cutaneous toxicities associated with radiotherapy and systemic
chemotherapy, including epidermal growth factor inhibitors and monoclonal
antibodies. The experts hope that these recommendations will improve the
management of cutaneous side effects and hence quality of life for oncology
patients.
PMID- 24353441
TI - Estimating the prevalence of atrial fibrillation in a general population using
validated electronic health data.
AB - BACKGROUND: The purpose of this study was to determine the prevalence of atrial
fibrillation (AF) in the general population and to validate an administrative
diagnosis register, ie, the National Patient Register (NPR), and an
electrocardiography (ECG) database in estimating disease prevalence. METHODS: The
study was conducted in a well defined region in northern Sweden (population
n=75,945) which consists of one hospital and eleven primary health care centers.
Subjects with AF were identified by searching the combined inpatient and
outpatient International Classification of Diseases (ICD)-based NPR (ICD-10 code
I48) and an ECG database with computer-interpreted AF from January 1, 2004 to
December 31, 2010. All identified cases with AF were validated. RESULTS: AF was
confirmed in 2,274 patients. The overall prevalence was 3.0% (3.4% in men and
2.6% in women). AF prevalence rose steadily with age, and was 16.8% in patients
aged 75 years and older and 21.9% in patients 85 years and older. Of all patients
with validated AF, the NPR identified 93.2%. The ECG database identified an
additional 6.8%, of which 81% were over 70 years of age. According to the NPR,
the proportion of false positives and false negatives was 3.5% and 6.8%,
respectively. The corresponding figure for the ECG database was 11.3% and 9.2%,
respectively. CONCLUSION: Our study shows a high prevalence of AF, especially
among the elderly. Searching the ECG database enhanced the detection of AF. The
reliability of the NPR was high, with a relatively low proportion of false
positives and negatives.
PMID- 24353442
TI - Maternal and neonatal outcomes of placenta previa and placenta accreta: three
years of experience with a two-consultant approach.
AB - OBJECTIVE: The aim of this retrospective cohort study was to evaluate maternal
and neonatal outcomes in patients with placenta previa (PP) and placenta accreta
(PA). METHODS: The study population comprised all patients who had a cesarean
section for PP and PA at a tertiary referral hospital in Taif, Kingdom of Saudi
Arabia, from December 2009 to December 2012. Maternal and neonatal data were
obtained from medical records and the hospital database system. PA cases were
managed by a multispeciality team, including two obstetric consultants. RESULTS:
In total, 122 patients with PP were identified, with PA found in 25 cases. The
median intraoperative blood loss in cases of PA was 2,000 (mean 3,000) mL, with a
loss of >=2,000 mL occurring in 72%, and >=5,000 mL in 20%. The median packed red
blood cell transfusion requirement was 6 (mean 7.7) units, and 28% received >=10
units. Fetal growth restriction was diagnosed in two cases with known maternal
medical disorders. Four cases (3.3%) were diagnosed as small for gestational age.
The mean birth weight of the neonates was at the 10th-50th percentile according
to Hadlock fetal growth charts. CONCLUSION: The presence of a second obstetric
consultant among the multispeciality team during surgery for PA was associated
with a reduction in blood loss and a decreased need for large-volume blood
transfusion. The rate of fetal growth restriction/small for gestational age in PP
was average, but the babies were relatively small (level 2 evidence).
PMID- 24353443
TI - Neurological syndrome in an HIV-prevention trial participant randomized to daily
tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) in Bondo,
Kenya.
AB - Side effects of antiretroviral drug use by HIV-positive patients have been
extensively studied; however, there are limited data on the side effects of
antiretroviral drugs used as an HIV prophylaxis among healthy, HIV-negative
individuals. Here we report on an unusual neuropathy in a 24-year-old participant
in the FEM-PrEP trial. This was a Phase III randomized, double blind, placebo
controlled trial to test the safety and effectiveness of tenofovir disoproxil
fumarate (300 mg) and emtricitabine (200 mg) (TDF-FTC) to prevent HIV. At the
eighth week of taking TDF-FTC with moderate adherence, the participant complained
of mild paresthesiae, numbness, and a tingling sensation in her upper limbs that
was associated with pain and cold. After an additional 4 days, she developed a
disabling weakness of her upper limbs and tremors in her hands. The study product
was discontinued, and within 2 weeks she was free of all symptoms. One month
after restarting the drug, she complained of posture-dependent numbness of her
upper limbs. Results of clinical and neurological exams, laboratory tests, and
magnetic resonance imaging are described here.
PMID- 24353444
TI - Lyme disease: case report of persistent Lyme disease from Pulaski County,
Virginia.
AB - A 50-year-old woman from Pulaski, Virginia, presented to a local clinic with
headaches, fever, generalized joint pain, excessive thirst and fluid intake, and
a progressing rash on her back. On physical examination, she had a large circular
red rash on her back with a bull's-eye appearance, 16 * 18 cm in diameter.
Serologic tests confirmed a diagnosis of Lyme disease. The patient could recall a
walk through the woods 3 weeks prior, although she never noticed a tick on her
body. Following a prolonged course of antibiotics, this case report presents a
patient with ongoing symptoms consistent with post-treatment Lyme disease.
PMID- 24353445
TI - Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of
apixaban in healthy Chinese subjects.
AB - BACKGROUND: The pharmacokinetics (PK), pharmacodynamics (PD), and safety of
apixaban were assessed in healthy Chinese subjects in this randomized, placebo
controlled, double-blind, single-sequence, single- and multiple-dose study.
SUBJECTS AND METHODS: Eighteen subjects 18-45 years of age were randomly assigned
(2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10
mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo
twice daily for 6 days (days 4-9). The PK and PD of apixaban were assessed by
collecting plasma samples for 72 hours following the dose on day 1 and the
morning dose on day 9, and measuring apixaban concentration and anti-Xa activity.
Safety was assessed via physical examinations, vital sign measurements,
electrocardiograms, and clinical laboratory evaluations. RESULTS: PK analysis
showed similar characteristics of apixaban after single and multiple doses,
including a median time to maximum concentration of ~3 hours, mean elimination
half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation
index was 1.7, consistent with twice-daily dosing and the observed elimination
half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are
time-independent. The relationship between anti-Xa activity and plasma apixaban
concentrations appears to be linear. Apixaban was safe and well tolerated, with
no bleeding-related adverse events reported. CONCLUSION: Apixaban was safe and
well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable
and consistent with findings from previous studies in Asian and non-Asian
subjects. The administration of apixaban does not require any dose modification
based on race.
PMID- 24353446
TI - Cytochrome P450 3A4*22, PPAR-alpha, and ARNT polymorphisms and clopidogrel
response.
AB - Recent candidate gene studies using a human liver bank and in vivo validation in
healthy volunteers identified polymorphisms in cytochrome P450 (CYP) 3A4 gene
(CYP3A4*22), Ah-receptor nuclear translocator (ARNT), and peroxisome proliferator
activated receptor-alpha (PPAR-alpha) genes that are associated with the CYP3A4
phenotype. We hypothesized that the variants identified in these genes may be
associated with altered clopidogrel response, since generation of clopidogrel
active metabolite is, partially mediated by CYP3A activity. Blood samples from
211 subjects, of mixed racial background, with established coronary artery
disease, who had received clopidogrel, were analyzed. Platelet aggregation was
determined using light transmittance aggregometry (LTA). Genotyping for
CYP2C19*2, CYP3A4*22, PPAR-alpha (rs4253728, rs4823613), and ARNT (rs2134688)
variant alleles was performed using Taqman(r) assays. CYP2C19*2 genotype was
associated with increased on-treatment platelet aggregation (adenosine
diphosphate 20 MUM; P=0.025). No significant difference in on-treatment platelet
aggregation, as measured by LTA during therapy with clopidogrel, was demonstrated
among the different genotypes of CYP3A4*22, PPAR-alpha, and ARNT. These findings
suggest that clopidogrel platelet inhibition is not influenced by the genetic
variants that have previously been associated with reduced CYP3A4 activity.
PMID- 24353447
TI - Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity
in uremic serum.
AB - There is a paucity of studies evaluating the change in liver metabolism in
subjects receiving hemodialysis. The purpose of this study was to compare the
effect of uremic toxins on hepatic cytochrome P450 (CYP)3A4 and CYP2D6 metabolism
before and after a 4-hour hemodialysis session. Midazolam and dextromethorphan
were incubated with uremic serum collected from subjects before and after the 4
hour hemodialysis session. Analysis and quantification of the 1'-OH-midazolam and
4-OH-midazolam and dextrorphan metabolites were performed by high-pressure liquid
chromatography/mass spectrometry. Statistical analysis using the Student's t-test
(paired) was used to compare the amount of metabolite formed. The mean amount of
1'-OH-midazolam, 4-OH-midazolam, and dextrorphan metabolites formed before and
after hemodialysis did not significantly differ. There was no significant
difference in CYP3A4 and CYP2D6 metabolic activity in uremic serum before and
after hemodialysis.
PMID- 24353448
TI - Special issue of clinical pharmacology: advances and applications in new protein
therapeutics modulating tumor immunity.
PMID- 24353449
TI - Benefits of monitoring patients with mobile cardiac telemetry (MCT) compared with
the Event or Holter monitors.
AB - INTRODUCTION: This research is meant to establish if a patient monitored with
mobile cardiac telemetry (MCT) sees different outcomes regarding diagnostic yield
of arrhythmia, therapeutic management through the use of antiarrhythmic drugs,
and cardiovascular costs incurred in the hospital setting when compared with more
traditional monitoring devices, such as the Holter or the Event monitor.
MATERIALS AND METHODS: We conducted a retrospective analysis spanning 57 months
of claims data from January 2007 to September 2011 pertaining to 200,000+
patients, of whom 14,000 used MCT only, 54,000 an Event monitor only, and 163,000
a Holter monitor only. Those claims came from the Truven database, an employer
database that counts 2.8 million cardiovascular patients from an insured
population of about 10 million members. We employed a pair-wise pre/post test
control methodology, and ensured that control patients were similar to test
patients along the following dimensions: age, geographic location, type of
cardiovascular diagnosis both in the inpatient and outpatient settings, and the
cardiovascular drug class the patient uses. RESULTS: First, the diagnostic yield
of patients monitored with MCT is 61%, that is significantly higher than that of
patients that use the Event monitor (23%) or the Holter monitor (24%). Second,
patients naive to antiarrhythmic drugs initiate drug therapy after monitoring at
the following rates: 61% for patients that use MCT compared with 39% for patients
that use the Event and 43% for patients that use the Holter. Third, there are
very significant inpatient cardiovascular savings (in the tens of thousands of
dollars) for patients that undergo ablation, coronary artery bypass graft (CABG)
and valve septa. Savings are more modest but nonetheless significant when it
comes to the heart/pericardium procedure. CONCLUSION: Given the superior outcome
of MCT regarding both patient care and hospital savings, hospitals only stand to
gain by enforcing protocols that favor the MCT system over the Event or the
Holter monitor.
PMID- 24353450
TI - A common signaling pathway is activated in erythroid cells expressing high levels
of fetal hemoglobin: a potential role for cAMP-elevating agents in beta-globin
disorders.
AB - BACKGROUND: Although erythroid cells prepared from fetal liver, cord blood, or
blood from beta-thalassemia patients are known to express fetal hemoglobin at
high levels, the underlying mechanisms remain elusive. We previously showed that
cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in
primary erythroid cells. Here we report that cAMP signaling contributes to high
level fetal hemoglobin expression in erythroid cells prepared from cord blood and
beta-thalassemia. METHODS: The status of the cAMP signaling pathway was
investigated using primary erythroid cells prepared from cord blood and the
mononuclear cells of patients with beta-thalassemia; erythroid cells from adult
bone marrow mononuclear cells served as the control. RESULTS: We found that
intracellular cAMP levels were higher in erythroid cells from cord blood and beta
thalassemia than from adult bone marrow. Protein kinase A activity levels and
cAMP-response element binding protein phosphorylation were higher in erythroid
cells from cord blood or beta-thalassemia than in adult bone marrow progenitors.
Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin
expression, were not consistently activated in cord blood or beta-thalassemia
erythroid cells. When cAMP signaling was activated in adult erythroid cells,
fetal hemoglobin was induced at high levels and associated with reduced
expression of BCL11A, a silencer of the beta-globin gene. CONCLUSION: These
results suggest that activated cAMP signaling may be a common mechanism among
erythroid cells with high fetal hemoglobin levels, in part because of
downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP
elevating agents may prove to be an important signaling mechanism to reactivate
fetal hemoglobin expression in erythroid cells.
PMID- 24353451
TI - Effect of a Growing-up Milk Containing Synbiotics on Immune Function and Growth
in Children: A Cluster Randomized, Multicenter, Double-blind, Placebo Controlled
Study.
AB - Common infectious diseases, such as diarrhea, are still the major cause of death
in children under 5-years-old, particularly in developing countries. It is known
that there is a close relationship between nutrition and immune function. To
evaluate the effect of a growing-up milk containing synbiotics on immune function
and child growth, we conducted a cluster randomized, multicenter, double-blind,
placebo controlled clinical trial in children between 18 and 36 months of age in
Vietnam. Eligible children from eight and seven kindergartens were randomly
assigned to receive test and isocaloric/ isoproteic control milk, respectively,
for 5 months. We found that the blood immunoglobulin A (IgA) level and growth
parameters were increased in the test group. Compared to the control group, there
was also a trend of decreased vitamin A deficiency and fewer adverse events in
the test group. These data suggest that a growing-up milk containing synbiotics
may be useful in supporting immune function and promoting growth in children.
PMID- 24353452
TI - Circular Conditional Autoregressive Modeling of Vector Fields.
AB - As hurricanes approach landfall, there are several hazards for which coastal
populations must be prepared. Damaging winds, torrential rains, and tornadoes
play havoc with both the coast and inland areas; but, the biggest seaside menace
to life and property is the storm surge. Wind fields are used as the primary
forcing for the numerical forecasts of the coastal ocean response to hurricane
force winds, such as the height of the storm surge and the degree of coastal
flooding. Unfortunately, developments in deterministic modeling of these forcings
have been hindered by computational expenses. In this paper, we present a
multivariate spatial model for vector fields, that we apply to hurricane winds.
We parameterize the wind vector at each site in polar coordinates and specify a
circular conditional autoregressive (CCAR) model for the vector direction, and a
spatial CAR model for speed. We apply our framework for vector fields to
hurricane surface wind fields for Hurricane Floyd of 1999 and compare our CCAR
model to prior methods that decompose wind speed and direction into its N-S and W
E cardinal components.
PMID- 24353453
TI - Parathyroid hormone and physical exercise: a brief review.
AB - Parathyroid hormone (PTH) is the major hormone regulating calcium metabolism and
is involved in both catabolic and anabolic actions on bone. Intermittent PTH
exposure can stimulate bone formation and bone mass when PTH has been injected.
In contrast, continuous infusion of PTH stimulates bone resorption. PTH
concentration may be affected by physical exercise and our review was designed to
investigate this relationship. The variation in PTH concentration appears to be
influenced by both exercise duration and intensity. There probably exists a
stimulation threshold of exercise to alter PTH. PTH regulation is also influenced
by the initial bone mineral content, age, gender, training state, and other
hormonal and metabolic factors (catecholamines, lactic acid and calcium
concentrations). Key PointsPhysical exercise can improve PTH
secretion.PARATHYROID HORMONE HAS BOTH ANABOLIC AND CATABOLIC EFFECTS ON BONE:
intermittent treatment of PTH is anabolic whereas continuous treatment is
catabolic.
PMID- 24353454
TI - Hemodynamic and lactic Acid responses to proprioceptive neuromuscular
facilitation exercise.
AB - The hemodynamic and metabolic responses to proprioceptive neuromuscular
facilitation (PNF) exercise were examined in 32 male university students (aged 19
28 years). Ten repetitions of PNF exercises were applied to the subjects'
dominant upper extremities in the following order: as an agonist pattern flexion,
adduction and external rotation; and as an antagonist pattern extension,
abduction and internal rotation. Heart rate (HR), systolic blood pressure (SBP),
diastolic blood pressure (DBP), double product (DP), and blood lactate
concentration (La) were determined before, immediately after, and at 1(st),
3(rd), and 5(th) minutes after PNF exercise. A one-way ANOVA with repeated
measures indicated significant differences in HR, SBP, DBP, DP and La immediately
after PNF exercise. HR increased from 81 (+/-10) to 108 (+/-15) b.min(-1) (p <
0.01), SBP increased from 117 (+/-10) to 125 (+/-11) mmHg (p < 0.01), DBP
increased from 71 (+/-10) to 75 (+/-8) mmHg (p < 0.01), DP increased from 96 (+/
16) to 135 (+/-24) (p < 0.01), and La increased from 0.69 (+/-0.31) to 3.99 (+/
14.63) mmol.L(-1) (p < 0.01). Thus PNF exercise resulted in increased hemodynamic
responses and blood lactate concentration that indicate a high strain on the
cardiovascular system and anaerobic metabolism in healthy subjects. Key PointsPNF
exercises resulted in increased hemodynamic responses.Repeated PNF exercises
resulted in an increased blood lactate concentration.
PMID- 24353455
TI - Influence of temperament and anxiety on athletic performance.
AB - Our research aimed to conduct basic descriptions of temperamental traits and the
level of state and trait anxiety of young male athletes, and to compare them by
type of sports. Study participants were 277 athletes and 152 non-athletes who
were all high school boys. The Korean version of the Temperament and Character
Inventory (TCI) was used for checking temperamental traits while the Korean
version of the State and Trait Anxiety Inventory form Y (STAI-KY) was used to
estimate anxiety levels. Harm Avoidance score of athletes was higher than that of
non-athletes. Harm Avoidance score of golfers was lowest and that of swimmers was
highest. The state anxiety score of baseball players was lowest and that of
Taekwondo players was highest. The trait anxiety score of baseball players was
also lowest and that of golfers was highest. Both trait and state anxieties of
the 'winner' group were lower than those of the 'no winner' group. While prior
research mainly focused on athletes' environment and phenotypic characteristics,
we studied the pattern of temperaments in athletes along with its potential
influence on athletic performance. Key PointsHarm Avoidance score of athletes was
higher than that of non-athletes.Harm Avoidance score of golfers was lowest and
that of swimmers was highest.Both trait and state anxieties of the 'winner' group
were lower than those of the 'no winner' group.The trait anxiety score of
baseball players was also lowest while that of golfers was highest.
PMID- 24353456
TI - Effects of ballates, step aerobics, and walking on balance in women aged 50-75
years.
AB - This study examined the effectiveness of Ballates training (strengthening of the
central core musculature by the inception of balance techniques) compared to more
traditional exercise programs, such as step aerobics and walking, on balance in
women aged 50- 75 years. Participants were randomly assigned to one of three
supervised training groups (1 hour/day, 3 days/week, 13 weeks), Ballates (n =
12), step aerobics (n = 17), or walking (n =15). Balance was measured by four
different methods (modified Clinical Test for the Sensory Interaction on Balance
mCTSIB; Unilateral Stance with Eyes Open - US-EO or Eyes Closed - US-EC; Tandem
Walk - TW; Step Quick Turn - SQT) using the NeuroCom Balance Master. A 2-way
(Group and Trial) repeated measures ANOVA and post-hoc Bonferroni Pair-wise
Comparisons were used to evaluate changes in the dependent variables used to
describe stability and balance (sway velocity, turn sway, speed, and turn time).
Measures of static postural stability and dynamic balance were similar for the
three groups prior to training. Following the different exercise interventions,
sway velocity on firm and foam surfaces (mCTSIB) with eyes closed (p < 0.05)
increased for the Ballates group while the other two exercise groups either
maintained or decreased their sway velocity following the training, therefore
suggesting that these two groups either maintained or improved their balance.
There were significant improvements in speed during the TW test (p < 0.01), and
turn time (p < 0.01) and sway (p < 0.05) during the SQT test for each of the
three groups. In general, all three training programs improved dynamic balance,
however, step aerobics and walking programs resulted in be better improvements in
postural stability or static balance when compared to the Ballates program. Key
PointsExercise training can improve balanceNeed to consider both static and
dynamic aspects of balance individuallyImproved balance can reduce the risk of
fall.
PMID- 24353457
TI - The influence of body position on load range during isokinetic knee
extension/flexion.
AB - ISOKINETIC RANGE OF MOTION (ROM) HAS THREE DISTINCT PHASES: rate of velocity
development (RVD), load range (LR), and deceleration (DCC). The purpose of this
study was to determine if differences in isokinetic knee extension/flexion LR
exist between body positions. Ten subjects (4 males and 6 females, age 29.3 +/-
5.4 yrs, ht 1.71 +/- 0.10 m, wt 71.9 +/- 12.9 kg) volunteered to participate in
the seated vs. prone investigation and nine different subjects (4 males and 5
females, age 29.5 +/- 6.9 yrs, ht 1.72 +/- 0.09 m, wt 69.0 +/- 13.8 kg)
volunteered to participate in the seated vs. supine study. Each subject completed
3 maximal reciprocal concentric/concentric repetitions of dominant knee
extension/flexion on a Biodex System 2 isokinetic dynamometer at 60, 120, 180,
240 and 360 deg.sec(-1) in the supine or prone and seated positions. Repeated
measures ANOVA revealed that only seated flexion at 360 deg.sec(-1) (57.6 +/- 1.7
degrees) elicited significantly (p < 0.05) greater LR than prone (49.2 +/- 2.8
degrees). No significant differences in LR extension or flexion existed at any
velocity between the supine vs. seated positions. ANOVA also demonstrated
differences between seated vs. prone torque, work and power at most velocities
while there was no difference between seated vs. supine. LR is the only phase of
an isokinetic repetition where quantifiable resistance is maintained and this
data appears to support that it may not be position-dependent but position may
alter traditional performance variables. Key PointsLoad range is the constant
velocity phase where torque is collected.Load range has an inverse relationship
with velocity.Load range may not be position dependent for the knee extensors or
flexors.
PMID- 24353458
TI - Ephedra use in a select group of adolescent athletes.
AB - Ephedra-containing dietary supplements are consumed to improve sports performace,
but may carry risks of cardiac and neurological adverse events. Little is known
of their use by young athletes. Our aim was to determine the prevalence and
patterns of ephedra use among high school athletes. An anonymous survey was
performed in Rochester, Minnesota on high school athletes who participated in
fall sports during 2003-04. Parental consent was obtained for athletes under age
18 years. Surveys were distributed at preparticipation examinations and in-
school survey stations. The response rate to the survey was 68.2%, or 311
respondents out of a possible 456 with consent (or 26% of all 1197 athletes
eligible prior to the consent process). Seven of 311 (2.3%) respondents used
dietary supplements containing ephedra. Only one of seven users (14.3%) knew that
the supplements they used contained ephedra. Ephedra use was more common in boys
(five) than girls (two). Ephedra use was only found in 17 and 18-year-olds. The
most common sports among ephedra users were football, track and field, and
weightlifting. This study suggests that Ephedra use was infrequent among the
young athletes in this population. However, ephedra users were generally unaware
that the dietary supplements they consumed contained ephedra. Users were more
likely to participate in football, track and field, and weightlifting. Ephedra
users were likely to obtain supplements from their peers, and were largely
uninformed of the content of their supplements. Key PointsEphedra is an herbal
stimulant used as an ergogenic aide.Adolescent ephedra users most commonly obtain
it from their friends.Adolescent athletes are likely to take ephedra
unknowningly.
PMID- 24353459
TI - Psychological skills usage and the competitive anxiety response as a function of
skill level in rugby union.
AB - This study examined the intensity and direction of competitive anxiety symptoms
and psychological skill usage in rugby union players of different skill levels.
Elite (n=65) and nonelite (n=50) participants completed measures of competitive
anxiety, self- confidence, and psychological skills. The elite group reported
more facilitative interpretations of competitive anxiety symptoms, higher levels
of self-confidence, lower relaxation usage, and greater imagery and self-talk use
than their nonelite counterparts. The findings suggest that nonelite performers
primarily use relaxation strategies to reduce anxiety intensity. In contrast,
elite athletes appear to maintain intensity levels and adopt a combination of
skills to interpret symptoms as facilitative to performance. Potential mechanisms
for this process include the use of imagery and verbal persuasion efficacy
enhancement techniques to protect against debilitating symptom interpretations.
Key PointsNonelite performers primarily use relaxation strategies to reduce
anxiety intensity.Elite athletes maintain intensity levels and adopt a
combination of psychological skills to interpret symptoms as facilitative.This
process occurs through imagery and verbal persuasion efficacy-enhancement
techniques.Nonelite performers who are debilitators should implement relaxation
based programs. However, in high activation level sports performers should reduce
symptom intensity, restructure cognitions, and then raise activation states again
to appropriate levels.Elite performers who are debilitators should implement
cognitive restructuring techniques to interpret their anxiety as facilitative via
a combination of goal setting, self-talk, and imagery.
PMID- 24353460
TI - Effect of intermittent sub-maximal exercise on percent body fat using leg-to-leg
bioelectrical impedance analysis in children.
AB - The purpose of this investigation was to determine the effect of intermittent sub
maximal exercise on percent body fat (%BF) estimated by leg-to-leg bioelectrical
impedance analysis (LBIA) in children. Fifty-nine children (29 girls; 30 boys)
mean age 9.0 +/- 1.3 years participated in this study. LBIA measured %BF values
were obtained immediately before and within five minutes after completing an
intermittent exercise protocol consisting of three 8-minute sub-maximal exercise
bouts (2.74 km.hr(-1), 0% grade; 4.03 km.hr(-1), 0% grade; and 5.47 km.hr(-1), 0%
grade) each separated by a 5-min seated rest period. The three exercise bouts
corresponded to 56%, 61% and 71% of maximal heart rate. Significant differences
(p < 0.001) were observed for fat mass, fat free mass, total body water, and body
weight, post-exercise in both groups. Significant reductions (p < 0.001) in %BF
were observed post-exercise in the female (23.1 +/- 9.9 vs. 21.8 +/- 9. 9 %) and
male (23.3 +/- 10.5 vs. 21.8 +/- 10.2 %) children when compared to pre-exercise
values. However, for the majority of the subjects (females = 86%; males = 73%)
the decrease in %BF post- exercise was less than 2.0 %BF. These data indicate
that sub-maximal intermittent exercise, that may be representative of daily free
form activities in children, will most likely have a limited impact on %BF
estimates when the assessment is performed immediately post-exercise. Key
PointsLBIA measures of body weight, percent body fat, fat mass, fat free mass and
total body water were significantly lower after the intermittent sub-maximal
exercise.The reductions in percent body fat for girls (1.4%) and boys (1.5%)
compare favorably to previous investigations.Intermittent exercise, that may be
representative of daily free-form activities in children, will most likely have a
limited impact on LBIA percent body fat estimates.
PMID- 24353461
TI - Effects of a Basketball Activity on Lung Capillary Blood Volume and Membrane
Diffusing Capacity, Measured by NO/CO Transfer in Children.
AB - In both children and adults, acute exercise increases lung capillary blood volume
(Vc) and membrane factor (DmCO). We sought to determine whether basketball
training affected this adaptation to exercise in children. The purpose of this
study was to determine the effects of two years sport activity on the components
of pulmonary gas transfer in children. Over a 2-yr period, we retested 60 nine
year old boys who were initially separated in two groups: 30 basketball players
(P) (9.0 +/- 1.0 yrs; 35.0 +/- 5.2 kg; 1.43 +/- 0.05 m), and matched non players
controls (C) (8.9 +/- 1.0 yrs; 35.0 +/- 6.0 kg; 1.44 +/- 0.06 m) who did not
perform any extracurricular activity, Vc and DmCO were measured by the NO/CO
transfer method at rest and during sub-maximal exercise. Maximal aerobic power
and peak power output was 12% higher in the trained group compared to matched
controls (p < 0.05). Nitric oxide lung transfer (TLNO) per unit lung volume and
thus, DmCO per unit of lung volume (VA) were higher at rest and during exercise
in the group which had undergone regular basketball activity compared to matched
controls (p < 0.05). Neither lung capillary blood volume nor total lung transfer
for carbon monoxide (TLCO) were significantly different between groups. These
results suggest that active sport can alter the properties of the lung alveolo
capillary membrane by improving alveolar membrane conductance in children. Key
PointsTrained children had greater DmCO/VA and DmCO/Vc ratios compared with
control children during exercise.The mechanisms by which basketball playing
children were thought to improve lung diffusion are speculative.Further work will
be required to determine the kinetics of the alteration in Dm when children
switch from non players to players status or vice-versa.
PMID- 24353463
TI - Recommendations regarding exercise during pregnancy made by private/small group
practice obstetricians in the USA.
AB - For pregnant women, exercise offers numerous benefits with little risk. The
American College of Obstetricians and Gynecologists (ACOG) endorses aerobic
exercise for all pregnant women without medical or obstetric complications.
Nonetheless, only a small percentage of pregnant women meet exercise guidelines.
We investigated the extent to which obstetricians (Obs) in private or small group
practice in the USA actively recommend exercise to their pregnant patients.
Surveys were sent to 300 Obs in 33 American cities, of which 83 were returned.
52% of respondents reported discussing exercise with 81-100% of their patients.
Using a 7- point Likert scale (1 = never, 7 = always), Obs reported recommending
aerobic exercise more often than resistance exercise (5.6 +/- 1.5 versus 3.8 +/-
1.6, p < 0.001). Obs do not routinely advise sedentary women to initiate exercise
during pregnancy (mean 4.4 +/- 1.8). Of the 67% of Obs who specify a target
exercise duration, 95% recommend >= 16 min, consistent with ACOG guidelines.
However, 62% of Obs reported that they regularly specify a maximum heart rate,
even though ACOG guidelines do not. Half of respondents indicated that they
advise a reduction in exercise load during the third trimester, even for
uncomplicated pregnancies. Respondents' opinions were mixed regarding the extent
to which exercise reduces gestational diabetes or preeclampsia risk and they
believe more research on exercise during pregnancy is needed. Half of Obs do not
routinely discuss exercise. The majority is hesitant to advise sedentary gravidae
to start exercise and is conservative with respect to exercise intensity. Action
may be needed to convince more Obs to routinely recommend exercise to all healthy
patients. Key Points52% of surveyed obstetricians discuss exercise with 81-100%
of pregnant patients.68% of surveyed obstetricians do not regularly advise
sedentary pregnant women to initiate an exercise program.62% of surveyed
obstetricians recommend pregnant patients not exceed a maximum heart rate during
exercise, even though ACOG guidelines do not specify a maximum heart
rate.Approximately half of surveyed obstetricians recommend a reduction in
exercise load during the third trimester, even though ACOG guidelines do
not.Regular exercise was thought by surveyed obstetricians to have some potential
for reducing the risk of gestational diabetes, but little effect on risk of
preeclampsia.
PMID- 24353462
TI - Muscle Fatigue Increases Metabolic Costs of Ergometer Cycling without Changing
VO2 Slow Component.
AB - The aim of the present study was to investigate effects of muscle fatigue on
oxygen costs of ergometer cycling and slow component of pulmonary oxygen uptake
(VO2) kinetics. Seven young men performed 100 drop jumps (drop height of 40 cm)
with 20 s of rest after each jump. After the subsequent hour of rest, they cycled
at 70, 105, 140 and 175 W, which corresponded to 29.6 +/- 5.4, 39.4 +/- 7.0, 50.8
+/- 8.4 and 65.8 +/- 11.8 % of VO2peak, respectively, for 6 min at each intensity
with 4-min intervals of rest in between the exercise bouts. The VO2 response to
cycling after the exercise (fatigue condition) was compared to ergometer cycling
without prior exercise (control condition). From 3rd to 6th min of cycling at
105, 140 and 175 W, VO2 was higher (p < 0.05-0.01) when cycling in the fatigue
compared to the control condition. Slow component of VO2 kinetics was observed
when cycling at 175 W in the control condition (0.17 +/- 0.09, l.min(-1), mean +/
SD), but tended to decrease in the fatigue condition (0.13 +/- 0.15 l.min(-1)).
In summary, results of the study are in agreement with the hypothesis that muscle
fatigue increases oxygen costs of cycling exercise, but does not affect
significantly the slow component of pulmonary oxygen uptake (VO2) kinetics. Key
PointsRepetitive fatiguing exercise induce an increase in metabolic costs of
ergometer cycling exercise.It is argued that muscle pain, muscle temperature,
elevated pulmonary ventilation and heart rate, shift towards from carbohydrate to
fat metabolism are of minor importance in this phenomenon.Increased recruitment
of type II fibres and impaired force transmission between muscle fibres due to
damage of structural proteins appear to play the major role in reducing
efficiency of ergometer cycling.
PMID- 24353464
TI - The effects of a 6-week plyometric training program on agility.
AB - The purpose of the study was to determine if six weeks of plyometric training can
improve an athlete's agility. Subjects were divided into two groups, a plyometric
training and a control group. The plyometric training group performed in a six
week plyometric training program and the control group did not perform any
plyometric training techniques. All subjects participated in two agility tests: T
test and Illinois Agility Test, and a force plate test for ground reaction times
both pre and post testing. Univariate ANCOVAs were conducted to analyze the
change scores (post - pre) in the independent variables by group (training or
control) with pre scores as covariates. The Univariate ANCOVA revealed a
significant group effect F2,26 = 25.42, p=0.0000 for the T-test agility measure.
For the Illinois Agility test, a significant group effect F2,26 = 27.24, p =
0.000 was also found. The plyometric training group had quicker posttest times
compared to the control group for the agility tests. A significant group effect
F2,26 = 7.81, p = 0.002 was found for the Force Plate test. The plyometric
training group reduced time on the ground on the posttest compared to the control
group. The results of this study show that plyometric training can be an
effective training technique to improve an athlete's agility. Key
PointsPlyometric training can enhance agility of athletes.6 weeks of plyometric
training is sufficient to see agility results.Ground reaction times are decreased
with plyometric training.
PMID- 24353466
TI - Dynamic compaction of granular materials.
AB - An Eulerian hyperbolic multiphase flow model for dynamic and irreversible
compaction of granular materials is constructed. The reversible model is first
constructed on the basis of the classical Hertz theory. The irreversible model is
then derived in accordance with the following two basic principles. First, the
entropy inequality is satisfied by the model. Second, the corresponding
'intergranular stress' coming from elastic energy owing to contact between grains
decreases in time (the granular media behave as Maxwell-type materials). The
irreversible model admits an equilibrium state corresponding to von Mises-type
yield limit. The yield limit depends on the volume fraction of the solid. The
sound velocity at the yield surface is smaller than that in the reversible model.
The last one is smaller than the sound velocity in the irreversible model. Such
an embedded model structure assures a thermodynamically correct formulation of
the model of granular materials. The model is validated on quasi-static
experiments on loading-unloading cycles. The experimentally observed hysteresis
phenomena were numerically confirmed with a good accuracy by the proposed model.
PMID- 24353465
TI - Effect of orthotics and footwear on static rearfoot kinematics.
AB - This study examined the effect of foot orthotics and footwear on static rearfoot
kinematics. Thirty-four subjects (5 males, 29 females) from physical therapy
clinics and the college community gave informed consent to participate. Subject
age was 42 (18) years; subject height was 1.7 (0.1) meters; subject body mass was
72.6 (12.1) kg. Markers were placed on specific sites of the lower leg and
calcaneus to determine the rearfoot angle. Rearfoot angle was measured with a
goniometer and digitized with video-based software (Ariel Performance Analysis
System). A calcaneal mold was utilized to determine the position of the calcaneus
in the shod conditions. Static rearfoot angles were measured in the following
conditions: barefoot (B), barefoot with the calcaneal mold (BM), barefoot with
the calcaneal mold plus the orthotic (BMO), shod with the calcaneal mold (SM),
and shod with the calcaneal mold plus the orthotic (SMO). An independent t-test
analyzed differences between each condition as measured with the APAS and
goniometer. A one-way analysis of variance (ANOVA) was utilized to determine
statistically significant differences among the 5 foot conditions (p <= 0.05).
Independent t-tests revealed no significant differences (p > 0.05) between the
APAS and goniometer measurements within each condition. One-way ANOVA showed a
significant difference (p <= 0.01) among the five conditions as measured by APAS.
Post-hoc analysis determined that the difference between BM and SM; and the BM
and SMO conditions were significantly different (p <= 0.01). It was observed that
the orthotic slightly decreased the amount of calcaneal eversion in the standing
position. The shoes worn in the study, though neutral in construction, did
significantly alter rearfoot kinematics in comparison to BM. Key PointsPrevious
literature concerning the effect of orthotics on lower extremity alignment is
inconclusive.This study concurs with the work of others as to the effectiveness
of orthotics on the reduction of calcaneal eversion.Even though the kinematic
differences were small, subjects still reported a positive effect on their level
of comfort with the orthotics as compared to not wearing the orthotic.
PMID- 24353467
TI - Inexact trajectory planning and inverse problems in the Hamilton-Pontryagin
framework.
AB - We study a trajectory-planning problem whose solution path evolves by means of a
Lie group action and passes near a designated set of target positions at
particular times. This is a higher-order variational problem in optimal control,
motivated by potential applications in computational anatomy and quantum control.
Reduction by symmetry in such problems naturally summons methods from Lie group
theory and Riemannian geometry. A geometrically illuminating form of the Euler
Lagrange equations is obtained from a higher-order Hamilton-Pontryagin
variational formulation. In this context, the previously known node equations are
recovered with a new interpretation as Legendre-Ostrogradsky momenta possessing
certain conservation properties. Three example applications are discussed as well
as a numerical integration scheme that follows naturally from the Hamilton
Pontryagin principle and preserves the geometric properties of the continuous
time solution.
PMID- 24353468
TI - Domain wall motion in magnetic nanowires: an asymptotic approach.
AB - We develop a systematic asymptotic description for domain wall motion in one
dimensional magnetic nanowires under the influence of small applied magnetic
fields and currents and small material anisotropy. The magnetization dynamics, as
governed by the Landau-Lifshitz-Gilbert equation, is investigated via a
perturbation expansion. We compute leading-order behaviour, propagation
velocities and first-order corrections of both travelling waves and oscillatory
solutions, and find bifurcations between these two types of solutions. This
treatment provides a sound mathematical foundation for numerous results in the
literature obtained through more ad hoc arguments.
PMID- 24353469
TI - Two-dimensional molecular magnets with weak topological invariant magnetic
moments: mathematical prediction of targets for chemical synthesis.
AB - An open problem in applied mathematics is to predict interesting molecules that
are realistic targets for chemical synthesis. In this paper, we use a spin
Hamiltonian-type model to predict molecular magnets (MMs) with magnetic moments
that are intrinsically robust under random shape deformations to the molecule.
Using the concept of convergence in probability, we show that for MMs in which
all spin centres lie in-plane and all spin centre interactions are ferromagnetic,
the total spin of the molecule is a 'weak topological invariant' when the number
of spin centres is sufficiently large. By weak topological invariant, we mean
that the total spin of the molecule depends only upon the arrangement of spin
centres in the molecule, and is unlikely to change under shape deformations to
the molecule. Our calculations show that only between 20 and 50 spin centres are
necessary for the total spin of these MMs to be a weak topological invariant. The
robustness effect is particularly enhanced for two-dimensional ferromagnetic MMs
that possess a small number of spin rings in the structure.
PMID- 24353470
TI - Nonlinear elastic inclusions in isotropic solids.
AB - We introduce a geometric framework to calculate the residual stress fields and
deformations of nonlinear solids with inclusions and eigenstrains. Inclusions are
regions in a body with different reference configurations from the body itself
and can be described by distributed eigenstrains. Geometrically, the eigenstrains
define a Riemannian 3-manifold in which the body is stress-free by construction.
The problem of residual stress calculation is then reduced to finding a mapping
from the Riemannian material manifold to the ambient Euclidean space. Using this
construction, we find the residual stress fields of three model systems with
spherical and cylindrical symmetries in both incompressible and compressible
isotropic elastic solids. In particular, we consider a finite spherical ball with
a spherical inclusion with uniform pure dilatational eigenstrain and we show that
the stress in the inclusion is uniform and hydrostatic. We also show how
singularities in the stress distribution emerge as a consequence of a mismatch
between radial and circumferential eigenstrains at the centre of a sphere or the
axis of a cylinder.
PMID- 24353471
TI - Large deformation contact mechanics of long rectangular membranes. I.
Adhesionless contact.
AB - In part I of this work, we study adhesionless contact of a long rectangular
elastic membrane with a rigid substrate. Our model is based on finite strain
theory and is valid for arbitrarily large deformations. Both frictionless and no
slip contact conditions are considered. Exact closed form solutions are obtained
for frictionless contact. For small contact, the differences between these two
contact conditions are small. However, significant differences occur for large
contacts. For example, frictionless contact predicts a maximum pressure (and
contact region) beyond which there is no solution; while the no-slip model places
no restriction on both quantities. The effect of adhesion will be considered in
part II of this work.
PMID- 24353472
TI - Large deformation contact mechanics of a pressurized long rectangular membrane.
II. Adhesive contact.
AB - In part I of this work, we presented a theory for adhesionless contact of a
pressurized neo-Hookean plane-strain membrane to a rigid substrate. Here, we
extend our theory to include adhesion using a fracture mechanics approach. This
theory is used to study contact hysteresis commonly observed in experiments.
Detailed analysis is carried out to highlight the differences between
frictionless and no-slip contact. Membrane detachment is found to be strongly
dependent on adhesion: for low adhesion, the membrane 'pinches-off', whereas for
large adhesions, it detaches unstably at finite contact ('pull-off'). Expressions
are derived for the critical adhesion needed for pinch-off to pull-off
transition. Above a threshold adhesion, the membrane exhibits bistability, two
stable states at zero applied pressure. The condition for bistability for both
frictionless and no-slip boundary conditions is obtained explicitly.
PMID- 24353473
TI - The implosion of cylindrical shell structures in a high-pressure water
environment.
AB - The implosion of cylindrical shell structures in a high-pressure water
environment is studied experimentally. The shell structures are made from thin
walled aluminium and brass tubes with circular cross sections and internal
clearance-fit aluminium end caps. The structures are filled with air at
atmospheric pressure. The implosions are created in a high-pressure tank with a
nominal internal diameter of 1.77 m by raising the ambient water pressure slowly
to a value, Pc, just above the elastic stability limit of each shell structure.
The implosion events are photographed with a high-speed digital movie camera, and
the pressure waves are measured simultaneously with an array of underwater blast
sensors. For the models with larger values of length-to-diameter ratio, L/D0, the
tubes flatten during implosion with a two-lobe (mode 2) cross-sectional shape. In
these cases, it is found that the pressure wave records scale primarily with Pc
and the time scale [Formula: see text] (where Ri is the internal radius of the
tube and rho is the density of water), whereas the details of the structural
design produce only secondary effects. In cases with smaller values of L/D0, the
models implode with higher-mode cross-sectional shapes. Pressure signals are
compared for various mode-number implosions of models with the same available
energy, PcV , where V is the internal air-filled volume of the model. It is found
that the pressure records scale well temporally with the time scale [Formula: see
text], but that the shape and amplitudes of the pressure records are strongly
affected by the mode number.
PMID- 24353474
TI - On using the levelling of the free surface of a Newtonian fluid to measure
viscosity and Navier slip length.
AB - Measuring the relaxation time involved in the levelling of a free surface of a
Newtonian fluid laid on a substrate can give access to material parameters. It is
shown here how most favourable pattern geometries of the free surface and film
thicknesses can be defined for the measures of viscosity and Navier slip length
at the fluid-solid interface, respectively. Moreover, we put special emphasis on
the conditions required to avoid shear thinning by controlling the maximum shear
rate. For initially sinusoidal patterns with infinitesimal amplitudes, an
analytical solution including slip at the fluid-solid interface is used, and
numerical simulations based on the natural element method allow one to discuss
the effect of finite amplitudes. This leads to the definition of a relevance
domain for the analytical solution that avoids the need for numerical simulations
in practical applications. It is also shown how these results can be applied to
crenelated profiles, where Fourier series expansion can be used, but with
caution.
PMID- 24353475
TI - A reasoned overview on Boussinesq-type models: the interplay between physics,
mathematics and numerics.
AB - This paper, which is largely the fruit of an invited talk on the topic at the
latest International Conference on Coastal Engineering, describes the state of
the art of modelling by means of Boussinesq-type models (BTMs). Motivations for
using BTMs as well as their fundamentals are illustrated, with special attention
to the interplay between the physics to be described, the chosen model equations
and the numerics in use. The perspective of the analysis is that of a
physicist/engineer rather than of an applied mathematician. The chronological
progress of the currently available BTMs from the pioneering models of the late
1960s is given. The main applications of BTMs are illustrated, with reference to
specific models and methods. The evolution in time of the numerical methods used
to solve BTMs (e.g. finite differences, finite elements, finite volumes) is
described, with specific focus on finite volumes. Finally, an overview of the
most important BTMs currently available is presented, as well as some indications
on improvements required and fields of applications that call for attention.
PMID- 24353477
TI - Relationship among Trust in Physicians, Demographics, and End-of-life Treatment
Decisions Made by African American Dementia Caregivers.
AB - PURPOSE: A pilot study was conducted in an urban African American community to
explore the relationship between trust in physicians, demographics and end-of
life treatment decisions made by African American caregivers of family members
with dementia: namely, cardiopulmonary resuscitation, mechanical ventilation and
tube feeding. METHODS: In a cross-sectional design, standard measures were
administered to a convenience sample of 68 African American caregivers of family
members with dementia. Univariate and multivariate analyses were used to explore
associations among the variables. RESULTS: Those with more education exhibited
higher (p = 0.035) trust in physicians than less educated individuals. Caregivers
who were more trusting of their physicians were more likely to use mechanical
ventilation (p = 0.0005) than were less trusting caregivers. Conversely, more
trusting caregivers were less likely to use tube feeding (p = 0.022).
CONCLUSIONS: Our findings suggest relationships exist among trust in physicians,
demographics and end-of-life treatment decisions. Thus, health care providers
should consider African American caregivers' perceived trust in physicians when
counseling about dementia and end-of-life treatment choices.
PMID- 24353476
TI - Effect of Ancillary Ligand on Electronic Structure as Probed by 51V Solid-State
NMR Spectroscopy for Vanadium-o-Dioxolene Complexes.
AB - A series of vanadium(V) complexes with o-dioxolene (catecholato) ligands and an
ancillary ligand, (N-(salicylideneaminato)ethylenediamine) (hensal), were
investigated using 51V solid-state magic angle spinning NMR spectroscopy (51V MAS
NMR) to assess the local environment of the vanadium(V). The solid-state 51V NMR
parameters of vanadium(V) complexes with a related potentially tetradentate
ancillary ligand (N-salicylidene-N'-(2-hydroxyethyl)ethylenediamine) (h2shed)
were previously shown to be associated with the size of the HOMO-LUMO gap in the
complex, and as such provide insights on the interaction between metal ion and
ligand (P. B. Chatterjee, et al., Inorg. Chem 50 (2011) 9794). Our results show
that the modification of the ancillary ligand does not impact the observed trend
between complexes ranging from catechols with electron rich to electron poor
substituents. However, the ancillary ligand does impact the size of the HOMO-LUMO
separation in the parent complex and thus the solid-state vanadium NMR chemical
shift of the unsubstituted vanadium complex. For these complexes significant
changes observed in the isotropic shifts and more modest changes detected in the
CQ reflect the electronic changes in the complex as the catechol is varied.
However, no obvious trend was observed in the chemical shift anisotropies
(deltasigma and etasigma) with the variation in the catechol. The electronic
changes in the coordination environment of the vanadium can be described using
solid-state 51V NMR spectroscopy.
PMID- 24353478
TI - Infants Show Ratio-dependent Number Discrimination Regardless of Set Size.
AB - Evidence for approximate number system (ANS) representations in infancy is robust
but has typically only been found when infants are presented with arrays of four
or more elements. In addition, several studies have found that infants fail to
discriminate between small numbers when continuous variables such as surface area
and contour length are controlled. These findings suggest that under some
circumstances, infants fail to recruit either the ANS or object file
representations for small sets. Here, we used a numerical change detection
paradigm to assess 6-month-old infants' ability to represent small values. In
Experiment 1, infants were tested with 1 versus 3, 1 versus 2, and 2 versus 3
dots. Infants successfully discriminated 1 versus 3 and 1 versus 2, but failed
with 2 versus 3. In Experiment 2, we tested whether infants could compare small
and large values with a 2 versus 4 condition. Across both experiments, infants'
performance exhibited ratio dependence, the hallmark of the ANS. Our results
indicate that infants can attend to the purely numerical attributes of small sets
and that the numerical change detection paradigm accesses ANS representations in
infancy regardless of set size.
PMID- 24353479
TI - Energetics of Multi-Ion Conduction Pathways in Potassium Ion Channels.
AB - Potassium ion channels form pores in cell membranes, allowing potassium ions
through while preventing the passage of sodium ions. Despite numerous high
resolution structures, it is not yet possible to relate their structure to their
single molecule function other than at a qualitative level. Over the past decade,
there has been a concerted effort using molecular dynamics to capture the
thermodynamics and kinetics of conduction by calculating potentials of mean force
(PMF). These can be used, in conjunction with the electro-diffusion theory, to
predict the conductance of a specific ion channel. Here, we calculate seven
independent PMFs, thereby studying the differences between two potassium ion
channels, the effect of the CHARMM CMAP forcefield correction, and the
sensitivity and reproducibility of the method. Thermodynamically stable ion-water
configurations of the selectivity filter can be identified from all the free
energy landscapes, but the heights of the kinetic barriers for potassium ions to
move through the selectivity filter are, in nearly all cases, too high to predict
conductances in line with experiment. This implies it is not currently feasible
to predict the conductance of potassium ion channels, but other simpler channels
may be more tractable.
PMID- 24353480
TI - Perceptions of Longevity and Successful Aging in Very Old Adults.
AB - We examined perceptions of longevity and successful aging in young-old (60 to 74
years), old-old (75 to 89 years), and oldest-old (90 + years) adults drawn from
the Louisiana Healthy Aging Study (LHAS). Participants' responses to three open
ended questions that assessed their attributions for longevity, what they look
forward to, and advice for younger persons today were compared. Content analyses
yielded three emergent themes: maintaining physical, mental, and relational well
being; living a healthy life; and living a faithful life. Implications of these
findings for current views on successful aging and insights for promoting a long
and healthy life are considered.
PMID- 24353482
TI - Self-efficacy: Implications for Physical Activity, Function, and Functional
Limitations in Older Adults.
AB - Attenuating the physical decline and increases in disability associated with the
aging process is an important public health priority. Evidence suggests that
regular physical activity participation improves functional performance, such as
walking, standing balance, flexibility, and getting up out of a chair, and also
plays an important role in the disablement process by providing a protective
effect against functional limitations. Whether these effects are direct or
indirect has yet to be reliably established. In this review, the authors take the
perspective that such relationships are indirect and operate through self
efficacy expectations. They first provide an introduction to social cognitive
theory followed by an overview of self-efficacy's reciprocal relationship with
physical activity. They then consider the literature that documents the effects
of physical activity on functional performance and functional limitations in
older adults and the extent to which self-efficacy might mediate these
relationships. Furthermore, they also present evidence that suggests that self
efficacy plays a pivotal role in a model in which the protective effects
conferred by physical activity on functional limitations operate through
functional performance. The article concludes with a brief section making
recommendations for the development of strategies within physical activity and
rehabilitative programs for maximizing the major sources of efficacy information.
PMID- 24353484
TI - The Enantioselective Addition of Alkyne Nucleophiles to Carbonyl Groups.
AB - Over the past decade, large strides have been achieved in the invention of
methods for the direct enantioselective addition of alkynes and metal alkynylide
nucleophiles into prochiral aldehydes, ketones, and imines. This review
highlights and compares the available methods for these transformations.
PMID- 24353485
TI - Role of E-selectin and platelet endothelial cell adhesion molecule 1 in gastritis
in food allergy patients.
AB - INTRODUCTION: The prevalence of food allergies and other allergic reactions is
increasing worldwide, particularly in highly-urbanized populations. Cell adhesion
molecules are expressed in response to various pro-inflammatory cytokines. The
expression of intercellular adhesion molecule 1 - ICAM-1 (CD54), ICAM-1 (CD106),
P-selectin (CD62P), and E-selectin (CD62E) on vascular endothelial cells is
induced by such pro-inflammatory cytokines as tumor necrosis factor alpha (TNF
alpha) and interleukin-1 (IL-1). AIM: To analyze concentrations of E-selectin and
platelet endothelial cell adhesion molecule-1 (PECAM-1) in patients with an
allergic type of food sensitivity co-existing with gastritis and to compare them
to the values determined in individuals with dyspeptic symptoms not associated
with allergic disorders. MATERIAL AND METHODS: The study included 80 patients,
among them 50 individuals with food sensitivity confirmed based on compulsory
standards, and 30 subjects with dyspeptic symptoms not accompanied by allergic
conditions. Venous blood samples were taken from each patient and concentrations
of E-selectin and PECAM-1 were determined by means of ELISA. RESULTS: Mean
concentrations of sE-selectin and sPECAM-1 in patients with food allergy amounted
to 54.0 +/-21.6 ng/ml and 132.8 +/-31.4 ng/ml, respectively. In individuals
without food allergy, mean concentrations of sE-selectin and sPECAM-1 were 57.7
+/-17.9 ng/ml and 139.6 +/-31.1 ng/ml, respectively. Patients with food allergy
and individuals with dyspeptic symptoms not associated with food allergy did not
differ significantly in terms of sE-selectin concentrations (Mann-Whitney U-test,
p = 0.453028). Similarly, no significant intergroup differences were observed
with regard to sPECAM-1 concentrations (Mann-Whitney U-test, p = 0.231054).
CONCLUSIONS: Adhesion molecules play an important role in the development of
inflammation. This study did not find significant differences in the
concentrations of such molecules as sE-selectin and sPECAM-1 between patients
with food allergy and gastritis, and subjects in whom gastritis was not
accompanied by atopic disorders. A positive correlation between the
concentrations of sPECAM-1 and E-selectin was observed in food allergy patients.
Consequently, it can be concluded that these molecules participate in the
pathogenesis of the inflammatory process independently of the etiopathogenesis of
gastritis.
PMID- 24353483
TI - Protection and Restitution of Gut Barrier by Probiotics: Nutritional and Clinical
Implications.
AB - Probiotics are beneficial bacteria present in various dietary components and many
of these colonize in the human and animal intestine. In the gut probiotics help
the host by assisting in maintenance of normal mucosal homeostasis. Probiotics
not only help maintain normal function of the gut mucosa, but also protect mucosa
from injurious factors such as toxins, allergens and pathogens. The beneficial
effect of probiotics is mediated by multiple mechanisms, including
cytoprotection, cell proliferation, cell migration, resistance to apoptosis,
synthesis of proteins and gene expression. One of the important cytoprotective
effects of probiotics in the intestinal mucosa is to strengthen the epithelial
tight junctions and preservation of mucosal barrier function. Probiotics not only
enhance barrier function by inducing synthesis and assembly of tight junction
proteins, but also preventing disruption of tight junctions by injurious factors.
Bioactive factors released by probiotics trigger activation of various cell
signaling pathways that lead to strengthening of tight junctions and the barrier
function. This article reviews and summarizes the current understanding of
various probiotics that are involved in the protection of gut barrier function,
highlights the cellular and molecular mechanisms involved in the protective
effect and addresses the clinical implications of probiotic supplementation.
PMID- 24353486
TI - Prevalence of atopic dermatitis in infants during the first six months of life:
authors' observations.
AB - INTRODUCTION: Atopic dermatitis (AD) is a frequent chronic skin disease in
infants. It creates great difficulties, both diagnostic and therapeutic. AIM: To
assess the prevalence of atopic dermatitis in infants during the first 6 months
of life. MATERIAL AND METHODS: The analysis comprised 2256 children at the age of
not more than 6 months, treated at the 2(nd) Department of Paediatrics and
Allergology of the Polish Mother's Memorial Hospital in Lodz, Poland, during
seven years. Out of all the patients, children with cutaneous changes were
isolated, and the location, type and aetiology of changes were assessed. RESULTS:
Dermal changes were diagnosed in 471 children, including 391 (17.3% of all the
patients) with atopic dermatitis. Out of the children with AD, IgE-dependent
allergy was identified in 39.9%. Cow's milk protein was the most frequent
sensitising allergen. In 71.6% of the infants, cutaneous changes were
disseminated and involved at least two areas of the body. All of them were
strongly itching. An applied elimination diet, together with anti-allergic
medications in some of the children, provided a clear clinical improvement.
CONCLUSIONS: Performed studies demonstrated the prevalence of atopic dermatitis
in 17.3% of examined children. The changes in children with AD were disseminated,
what was confirmed already at the infantile age. The obtained clinical
improvement after the applied therapy indicates a relationship between the
observed symptoms and allergic disease.
PMID- 24353487
TI - Correlation between serum interleukin-31 level and the severity of disease in
children with atopic dermatitis.
AB - INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease,
characterized by intense itch, typical localization and a specific image of skin
lesions. Pathogenesis of pruritus in AD is not fully understood, but recent
studies emphasize the role of interleukin-31 (IL-31). This relatively recently
described cytokine is considered to be a potential mediator inducing pruritus in
AD. AIM: To assess the correlation of serum IL-31 level and the disease severity
in children with AD. MATERIAL AND METHODS: Twenty-five children (16 girls and 9
boys) with AD aged from 4 months to 17 years (mean age: 4.2 years) were enrolled
in the study. Disease severity in children with AD was assessed using the SCORAD
(Severity SCORing of Atopic Dermatitis) index. Serum IL-31 levels were measured
using ELISA with standard kits from EIAab R&D Systems. RESULTS: Serum IL-31 level
was significantly higher in AD children than in healthy children. There was no
statistic correlation between serum IL-31 level and the disease severity or itch
intensity. CONCLUSIONS: The disease severity and itch intensity do not correlate
with serum IL-31 level in children with atopic dermatitis.
PMID- 24353488
TI - Neurogenic markers of the inflammatory process in atopic dermatitis: relation to
the severity and pruritus.
AB - INTRODUCTION: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin
disease, characterized by eczematous skin lesions and intensive pruritus. Recent
studies have shed light on the role of the nervous system in the pathogenesis of
AD. It can influence the course of the disease through an altered pattern of
cutaneous innervation and abnormal expression of neuropeptides in the lesional
skin. AIM: The aim of the study was to evaluate plasma concentrations of the
nerve growth factor (NGF), substance P (SP) and vasoactive intestinal peptide
(VIP) in AD patients in comparison to two control groups (healthy volunteers and
patients suffering from psoriasis). Correlations between plasma levels of
evaluated parameters, severity of the disease and selected clinical parameters
(skin prick tests, total and antigen specific IgE levels) were also analysed.
MATERIAL AND METHODS: Seventy-five patients with AD, 40 patients with psoriasis
and 40 healthy volunteers were included into the study. Patients with AD included
52 persons suffering from an extrinsic and 23 from an intrinsic type of the
disease. The severity of skin lesions was assessed with SCORAD index. Pruritus
was evaluated on the basis of the questionnaire assessing the extent, frequency
and intensity of pruritus. Commercial enzyme-linked immunosorbent assays (SP,
NGF: R&D Systems; and VIP: Phoenix Pharmaceuticals) were used to assess the
neuropeptide and NGF plasma levels. RESULTS: Nerve growth factor and VIP plasma
concentrations were significantly higher in AD patients compared to psoriatic
patients and healthy subjects. Substance P plasma concentrations were elevated in
the extrinsic type of AD and psoriasis comparing to healthy volunteers. There
were no statistically significant differences in NGF, SP and VIP plasma
concentrations between the extrinsic and intrinsic type of AD. There was also no
correlation between plasma levels of evaluated parameters (NGF, SP, VIP) and
SCORAD index in both types of AD. However, plasma SP concentration correlated
with intensity of pruritus in AD patients. Plasma VIP concentrations correlated
with intensity of pruritus in the intrinsic type of AD and with IgE-mediated
sensitization to moulds in the extrinsic type of disease. CONCLUSIONS: Our
findings confirm that NGF and VIP play a prominent role in atopic inflammatory
reactions and may serve as good alternative biomarkers of AD. The results of this
study also suggest a similar important role of neuroimmune interactions in both
variants of AD. Increased SP plasma concentrations in both AD and psoriasis point
to its possible role in modulating immune-mediated inflammation in different
chronic inflammatory skin diseases. Moreover, SP and VIP seem to influence the
course of AD by increasing pruritus, whereas an elevated plasma VIP level in AD
patients may be related to a risk of developing IgE-mediated sensitization to
certain airborne allergens.
PMID- 24353489
TI - Antifungal agents commonly used in the superficial and mucosal candidiasis
treatment: mode of action and resistance development.
AB - Recent progress in medical sciences and therapy resulted in an increased number
of immunocompromised individuals. Candida albicans is the leading opportunistic
fungal pathogen causing infections in humans, ranging from superficial mucosal
lesions to disseminated or bloodstream candidiasis. Superficial candidiasis not
always presents a risk to the life of the infected host, however it significantly
lowers the quality of life. Superficial Candida infections are difficult to treat
and their frequency of occurrence is currently rising. To implement successful
treatment doctors should be up to date with better understanding of C. albicans
resistance mechanisms. Despite high frequency of Candida infections there is a
limited number of antimycotics available for therapy. This review focuses on
current understanding of the mode of action and resistance mechanisms to
conventional and emerging antifungal agents for treatment of superficial and
mucosal candidiasis.
PMID- 24353490
TI - Age-dependent biomechanical properties of the skin.
AB - The skin fulfills one of its most important functions, that is protection from
mechanical injuries, due to the mechanism of reversible deformation of the
structure. Human skin is a complex living material but in biomechanical tests it
reveals its homogeneous nature. Biomechanical skin parameters change with time.
Results of thickness measurements, where the skin was subjected to pressure,
revealed that the Young's modulus increased linearly with age. The process of
ageing is the reason why the skin becomes thinner, stiffer, less tense and less
flexible. Skin tension measured during in vivo uniaxial load and the elasticity
modulus are higher in children than in elderly adults. Furthermore, mean ultimate
skin deformation before bursting is 75% for newborns and 60% for the elderly.
Several types of the main lines were distinguished on the skin. The static lines,
described by Langer, correspond to the lines of maximum tension, the Kraissl's
lines correspond to the movements of the skin during muscle work, whereas the
Borges lines are the relaxed skin tension lines. Biomechanical tests of the human
skin help to quantify the effectiveness of dermatological products, detect skin
diseases, schedule and plan surgical and dermatological interventions and
treatments.
PMID- 24353491
TI - Allergy to selected cosmetic ingredients.
AB - In an era in which cosmetics are commonly used, their often prolonged contact
with the human body should determine the safety of their use. Often cosmetics are
the cause of many side effects, mainly hypersensitivity reactions. Common groups
of cosmetic components responsible for side effects are fragrances, preservatives
and dyes. This paper focuses on the most allergenic components.
PMID- 24353492
TI - Farmers' occupational diseases of allergenic and zoonotic origin.
AB - Farmers are exposed to a number of biological, physical and chemical factors
harmful to the health, resulting from the specific nature of their work
environment. As is clear from epidemiological studies about occupational
diseases, pneumoconioses and infectious and parasitic diseases are recorded most
commonly. Due to the character of farmer's work, the greatest risk to his health
is biological hazards in the form of numerous microorganisms and their
metabolites, and particles of plants and animals contained in the organic dust
and pathogens transmitted by vectors such as ticks. The health status of farmers
is often worse than of other professional groups as a result of limited access to
health care and lower health literacy. Therefore, farmers should be subject to a
system of diagnosing occupational diseases, and many preventive and educational
programs concerning health risks associated with their work. The aim of this
paper is to characterize occupational diseases of farmers including allergic
diseases, tick-borne diseases and zoonoses.
PMID- 24353493
TI - "Mistletoe sign": probably a new dermoscopic descriptor for melanoma in situ and
melanocytic junctional nevus in the inflammatory stage.
AB - Melanomas in situ (MIS) are difficult to diagnose as they lack well-established,
dermoscopic descriptors. In numerous clinical cases, there are no definitive
differentiating criteria between atypical nevus and melanoma in situ. So far, no
digital dermoscopic criteria have been developed which can clearly distinguish
atypical naevi from MIS. It is necessary to search for predictors of MIS and
clinically suspected skin lesions in dermoscopy. We present 2 patients diagnosed
with and treated for melanoma in situ and junctional nevus in its inflammatory
stage. This includes a new morphological structure in dermoscopy known as the
"mistletoe sign". Below, we have described dermoscopic pictures, with appropriate
histopathology, for patients with the "mistletoe sign". Dermoscopy in two cases
revealed multiple, well-circumscribed areas, consisting of non-uniform, sometimes
pseudo-dichotomously branched structures, mimicking pseudopods, which were not
reticular, arising from overall reticular or homogenous patterns resembling the
mistletoe. Due to the fact that this is one of the several reports of its kind,
further research and observation are still necessary. The "mistletoe sign" may be
a descriptor of the melanocytic nevus in the inflammatory stage and the melanoma
in situ; however, further studies are necessary.
PMID- 24353494
TI - Therapeutic effects of CO2 laser therapy of linear nevus sebaceous in the course
of the Schimmelpenning-Feuerstein-Mims syndrome.
AB - The Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a rare phakomatosis which
comprises a nevus sebaceous of Jadassohn, seizures and developmental delay
associated with a wide spectrum of extracutaneous abnormalities including
neurological, skeletal, ocular, cardiovascular and urogenital defects. We are
presenting a case of an 18-year-old patient with systemic features of the SFM
syndrome and an extensive linear nevus sebaceous partially removed with a carbon
dioxide (CO2) laser. The treatment options of skin lesions in patients with SFM
are discussed.
PMID- 24353495
TI - Papuloerythroderma of Ofuji in a 41-year-old woman.
AB - Papuloerythroderma, described by Ofuji in 1984, is characterized by the
occurrence of polygonal, erythematous-brown papules, covering the entire skin
surface, except skin folds; these changes are accompanied by pruritus and
eosinophilia. We report a case of a 41-year-old female patient with
melanoerythroderma that has been intensifying since August 2010. The patient's
personal and family history for atopy were negative. No triggering factors were
identified in the course of hospitalizations. Preceding infections and neoplasms
were excluded. The diagnosis of papuloerythroderma of Ofuji was established on
the basis of major and minor criteria proposed by Torchia et al. The patient met
all the five major criteria: 1) erythroderma-like eruption formed by coalescence
of flat-topped, red-to-brown papules with a cobblestone-like appearance, 2) itch,
3) sparing of skin folds and creases, 4) histopathological exclusion of cutaneous
lymphoma and other skin diseases, 5) absence of the causative factors such as
tumors, infections, drugs and atopy. Regarding the 5 minor criteria, the patient
met the following three: 1) peripheral (33.8%) and tissue eosinophilia, 2)
elevated level of the total serum IgE (10935 IU/ml), 3) lymphopenia (6.6%). The
patient went into remission after 9-month treatment with cyclosporine at a dose
of 3 mg/kg.
PMID- 24353496
TI - Mixed connective tissue disease presenting with progressive scleroderma symptoms
in a 10-year-old girl.
AB - Mixed connective tissue disease (MCTD) is a systemic inflammatory disease
affecting connective tissue with the underlying autoimmunological mechanism. The
core of MCTD is an appearance of symptoms of several other inflammatory diseases
of connective tissue - systemic lupus erythematosus, systemic scleroderma, poly-
or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high
level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was
described more than 40 years ago by Sharp et al. During recent years, many
efforts to better understand clinical and serological features of MCTD have been
made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic
criteria are required to be fulfilled. Several versions of such criteria have
been proposed, but the most widely used one was described by Kasukawa. There is
no consensus about treatment - a choice of drugs depends on symptoms. We present
a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers
accompanied by symptoms of Raynaud's phenomenon. After an almost 2-year course of
the disease, a diagnosis of MCTD has been established.
PMID- 24353497
TI - Publication audit, Editor's Triage and Responsibilities of the Editors.
PMID- 24353498
TI - Views of Family Medicine Trainees of a Teaching Hospital in Riyadh regarding
their Hospital Rotations: A Qualitative Study.
AB - OBJECTIVE: To explore Family Medicine Trainees views regarding the hospital
component of their Family Medicine (FM) training program. METHODOLOGY: This is a
qualitative focus group discussion based study. Thirteen trainees, eight from
final year of FM training program and five from third year of the same program
participated in the study. The structure for discussion included a previously
distributed and completed questionnaire that included three sections. The first
section was evaluation of the satisfaction of trainees with the different
hospital specialties rotations. The second section related to reasons for rating
the different rotations as excellent and very good. The third section related to
deficiencies in training for those rotations which received a score of 3-5. The
items in the questionnaire were utilized in the focus group discussion. Two
facilitators who were investigators facilitated the discussion. The data was
qualitatively analyzed to identify emergent themes and subthemes that described
the trainees' views. RESULTS: The trainees highlighted the following views:
Teaching in the hospital component is not relevant to the needs of Family
Medicine trainees. Duration of the hospital posts should be reviewed. Emphasis
should be on out-patient clinics rather than in-patient. More emphasis must be
given to procedural skills, minor surgery and teaching in clinical contexts.
CONCLUSION: Hospital training component of the Family Medicine training program
should be reviewed, as the structure and its implementation doesn't reflect the
views of trainees regarding its relevance to their day to day practice.
PMID- 24353499
TI - Vitamin D levels in patients of acute leukemia before and after remission
induction therapy.
AB - OBJECTIVES: To determine the levels of 25-hydroxyvitamin [25(OH)D3] in patients
with acute leukemia and the effect of remission-induction chemotherapy.
METHODOLOGY: This study was case control, all newly diagnosed patients of acute
leukemia between the age of one to sixty years and residents of Pakistan were
enrolled and evaluated. Those who were unwilling or unable to provide written
informed consent were excluded. All selected patients (n=86) were grouped in to
acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was
further categorized as A1 before remission-induction (n=17) and B1 after
remission induction (n=13), ALL was further categorized as A2 before remission
induction (n=31) and B2 after remission induction (n=25). The 25-hydroxyvitamin
[25(OH)D3] levels were measured in the sera of all patients (before and after
remission-induction) by one step delayed chemiluminescent micro particle
immunoassay (CMIA).We compared 25(OH)D3 levels in all patients before and after
the remission-induction chemotherapy. RESULTS: A total of 86 patients were
analyzed, in which 60 patients were male. Mean age was 24.39 years (range, 1 to
60 years); the mean levels of 25(OH)D in group A1 (n=17) was 17.70+/-3.2 ng/ml,
in group B1 (n=13) 14.06+/-2.4 ng/ml, 19.07+/-7.08 ng/ml in group A2 (n=31),
while 10.59+/-3.9 ng/ml found in group B2 (n=25). CONCLUSION: 25(OH)D3
insufficiency was evident subnormal in majority of patients with acute leukemia
and 25(OH)D3 were further reduced after remission-induction as compared to
untreated group, difference was statistically significant when compared with each
group.
PMID- 24353500
TI - Frequency of Vitamin D deficiency in pregnant diabetics at Baskent University
Hospital, Istanbul.
AB - OBJECTIVE: To find out the frequency of vitamin D deficiency and its relation
with glucose parameters and the incidence of gestational diabetes (GDM).
METHODOLOGY: Gestational diabetes was diagnosed with 75 gram oral glucose
tolerance test. Forty-four pregnant women diagnosed with GDM and 78 non-GDM
pregnant women were enrolled as case and control group, respectively in this
descriptive study. Vitamin D status was classified as deficiency at <=20 ng/ml
for serum 25(OH)D concentrations. RESULTS: The mean ages were 33.4+/-5.2 (18-44)
years and 29.7+/-4.1 (21-39) years, mean BMI was 30.6+/-5.9 kg/m2 (19.5-46.1) and
25.9+/-4.4 kg/m2 (16.5-38) in case and control groups, respectively. The
frequency of GDM was found 9.38%. The mean serum vitamin D levels in GDM group
were significantly lower than in non-GDM subjects (p=0.07). A total of 56.8% of
GDM patients were compared with 35.8% of control group which had Vitamin D
deficiency and the difference was significant (p= 0.02). There was no significant
association between vitamin D levels and fasting glucose, insulin and HbA1c.
Vitamin D levels were inversely correlated with clothing style, parathyroid
hormone levels, dental problems and muscle cramps. CONCLUSIONS: The association
of maternal Vitamin D status with the markers of glucose metabolism in pregnancy
needs prospective studies.
PMID- 24353501
TI - Assessment of adipokines relationships with cardiovascular risk markers in
relation to body indices in normoglycemic males.
AB - OBJECTIVES: To evaluate the phenotypic relationship between obesity indices,
resistin, adiponectin and cardiovascular risk markers in normoglycemic healthy
individuals. METHODOLOGY: This cross-sectional study was conducted in the
Department of Physiology College of Medicine, King Saud University, Riyadh. A
total of 120 male subjects were selected for the study. All subjects underwent
analysis of body composition, glucose, glycosylated hemoglobin (HbA1c), lipids,
adiponectin, resistin, lipoprotein(a) and high sensitivity C reactive protein
(hsCRP). RESULTS: Body mass index (BMI) (r=0.326, p < 0.001), body fat mass (BFM)
(r=0.377, p < 0.001), body fat percentage (BF%) (r=0.326, p < 0.001), waist hip
ratio (WHR) (r=0.402, p < 0.001) and basal Insulin levels (r=0.217, p=0.018) were
positively correlated with hsCRP. However, serum adiponectin levels (r=0.189,
p=0.0391) were negatively correlated with hsCRP. Adiponectin levels were
significantly lower in obese compared to non obese subjects (p=0.0551). Keeping
hsCRP as dependant variable we observed that WHR, BFM, BF%, BMI and adiponectin
were significant predictors in univariate analysis. In multiple regression
analysis WHR and adiponectin were independent predictors of hsCRP. CONCLUSION:
Obese individuals have significantly higher levels of hsCRP levels and lower
adiponectin levels than non obese subjects. Serum adiponectin levels and WHR are
independant predictors of hsCRP levels in normoglycemic subjects.
PMID- 24353502
TI - Comparison of eutectic mixture of local anesthetics cream with dorsal penile
nerve block using lignocaine for circumcision in infants.
AB - OBJECTIVE: Circumcision is a commonly performed surgical procedure but choice of
anesthesia remained an issue of research and debate. This study was conducted to
find out the effectiveness of the eutectic mixture of local anesthetic (EMLA)
cream with dorsal penile nerve block (DPNB) using lignocaine, for reduction of
pain during circumcision. METHODOLOGY: This was comparative study carried out in
Surgical Unit B of National Institute of Child Health Karachi, from May 2008 to
October 2008. Patients under six month of age were randomized in to two groups
(EMLA and DPNB) of fifty patients each. The effectiveness of pain control was
assessed by measuring the baseline heart rate (HR), respiratory rate (RR) and
Neonatal infant Pain Scale (NIPS scale) before the start of procedure and
measuring of these parameters for each step of circumcision. Independent sample t
-test was used to compare means and repeated ANOVA was used to compare means of
HR, RR, oxygen (O2) saturations and NIPS. RESULTS: The mean age in both the
groups was 2.3 months. There was no statistically significant difference in
baseline parameters in both the groups except the respiratory rate, which was
significantly raised in DPNB group (33 breaths/min in EMLA and 38 in DPNB P <
0.04). During circumcision there was significant increase in heart rate in DPNB
group, especially in step three and step four (p < 0.04). Oxygen saturation
dropped in both the groups (baseline saturation 98% up to 91% in step 4). While
assessing NIPS scores in both the groups, statistically significant difference
was found between NIPS at step two and step four in two groups (p < 0.04).
CONCLUSIONS: The overall pain control was equal in both the groups, although NIPS
score was higher in DPNB in step two and four of circumcision. There was
difference in application and cost. EMLA was easy to apply but has increased
cost; while DPNB required expertise.
PMID- 24353503
TI - Ischaemic mitral regurgitation: The effects of ring annuloplasty and suture
annuloplasty repair techniques on left ventricular re-remodeling.
AB - OBJECTIVE: To examine the mid-term results of patients on whom a coronary
revascularization as well as a mitral ring and suture annuloplasty have been
performed due to coronary artery disease (CAD) and ischaemic mitral regurgitation
(IMR). METHODOLOGY: Totally 73 patients on whom a revascularization and a mitral
valve repair due to CAD and IMR had been performed in our clinic between 2000
2008 were included in the study. Patients were divided into two groups one of
which included 38 patients (52.05%) on whom a coronary artery bypass graft (CABG)
and a ring annuloplasty on the mitral valve had been performed (Group 1) and the
other one 35 patients (47.95%) on whom only suture annuloplasty as well as a CABG
had been performed (Group 2). The study was planned retrospectively and study
data have been obtained by screening the hospital registries retrospectively. In
the mid-term, patients were invited for a check and their intragroup and
intergroup echocardiographic parameters and functional capacities were assessed
statistically. RESULTS: In pre-operational and post-operational intragroup
assessment in terms of echocardiographic findings; although LVEDD, LVESD, EDV,
PAP and the degree of recurrent MR have been decreased in both groups, the
decrease in LVESD and PAP and the low degree of recurrent MR were statistically
significant in Group 1 patients (p=0.047, p=0.023, p=0.01, respectively). When
the mid-term intergroup echocardiograpic findings were assessed; PAP and
recurrent MR have been determined statistically lower in Group 1 patients
(p=0.005, p=0.08, respectively). The length of intensive care unit stay, length
of hospitalization and length of detachment from respiratory support were
statistically significantly longer in ring annuloplasty performed group (p=0.012,
p=0.033, p=0.029, respectively). CONCLUSIONS: In moderate to severe IMR patients,
a positive contribution can be provided to ventricular remodeling by a ring
annuloplasty through a significant decrease in left ventricular diameter and a
low recurrent MR and PAP.
PMID- 24353504
TI - XRCC1 Arg280His polymorphism and glioma risk: A meta-analysis involving 1439
cases and 2564 controls.
AB - OBJECTIVES: Previous reports indicated that XRCC1 Arg280His polymorphism might be
a possible risk factor for several cancers. Published studies on the association
of XRCC1 Arg280His polymorphisms with glioma risk have yielded controversial
results. The present study aimed to derive a more precise estimation of the
relationship. METHODOLOGY: Meta-analyses assessing the association of XRCC1
Arg280His variation with glioma were conducted and subgroup analyses on ethnicity
and source of controls were further performed. Eligible studies for the period up
to May 2012 were identified. RESULTS: A total of four case-control studies
comprising 1439 cases and 2564 controls were selected for analysis. The overall
data indicated no significant association of XRCC1 Arg280His polymorphism with
glioma risk (His vs Arg: OR=1.05; 95%CI=0.88-1.25; His/His vs Arg/Arg: OR=1.42;
95%CI=0.87-2.29; dominant model: OR=1.00; 95%CI=0.82-1.22; recessive model:
OR=1.41; 95%CI=0.88-2.25). Likewise, in the subgroup analysis regarding ethnicity
and source of controls, no associations were observed. CONCLUSION: The results of
the present study failed to suggest an association of XRCC1 Arg280His
polymorphism with glioma risk. Further large and well-designed studies are needed
to confirm this conclusion.
PMID- 24353505
TI - Functional outcome of flexor tendon repair of the hand at Zone 5 and post
operative early mobilization of the fingers.
AB - Objective : There are few reports on outcome following flexor tendon repair of
the hand in zone 5. We hypothesized that early mobilization of the fingers is
possible if the suture site of repaired tendon is strong enough. The aim of this
study was to assess the results of flexor tendon repair in this zone using
modified Kessler method reinforced by peripheral running suture and a post
operative early active and passive mobilization of the fingers. METHODOLOGY: This
prospective study was carried out between April 2006 and Feb 2010, and 171 digits
flexor tendons cut in 42 patients were repaired by modified Kessler technique
reinforced by running peripheral suture. Early active mobilization and gentle
passive motion of the fingers was allowed in a dorsal wrist splint the day after
surgery. Wrist Immobilization was performed for one month. Function of the
tendons was assessed by Buck-Gramcko score at nine month follow up. RESULTS: Mean
age of the patients was 25.4 years (range 17-46 y). Twenty nine flexor policis
longus, 77 flexor digitorum superficialis and 65 flexor digitorum profundus
tendons of digits were repaired. Middle and index fingers were most commonly
involved. Median and ulnar nerve repair was done in 17 and 12 cases respectively.
Good to excellent results were seen in of 79.34% of FPL and 74.65% of other
finger flexors. One case of FPL rupture was seen. Tenolysis of FDS was performed
in one case. Recovery in thenar muscle function was good, fair and poor in 5, 2
and 10 cases after median nerve repair, while all 12 patients with ulnar nerve
lesion showed some degrees of clawing of 4(th) and 5(th) fingers. Conclusion :
Most patients following flexor tendon repair at zone 5 obtained good results.
Early motion of the fingers seems to improve outcome in these patients.
Concomitant nerve cut in particular of ulnar nerve were associated with a high
rate of poor results.
PMID- 24353506
TI - Weekly dose of Iron-Folate Supplementation with Vitamin-C in the workplace can
prevent anaemia in women employees.
AB - OBJECTIVE: To assess if a weekly dose of iron and folic acid along with vitamin
C, in the workplace would reduce the prevalence of anaemia. METHODOLOGY: A multi
pronged intervention was carried out to reduce the prevalence of anaemia among
workers of 7 apparel manufacturing factories using a regime consisting of a
supervised single dose of albendazole (400mg) followed by a weekly dose of dried
ferrous sulphate (150mg), folic acid (0.5mg) and vitamin C (100mg). Workers were
provided information on the causes of anaemia and its prevention. The total
duration of the intervention was 16 weeks. Haemoglobin levels of a randomly
selected sample of workers were tested before and after the intervention using a
computerized non-cyan-meth-haemoglobin method. RESULTS: Of the 10810 workers who
were enrolled a sample of 515 workers was randomly selected for the blood
investigations. At the end of the intervention (18 weeks after the first blood
sample was collected) only 361 out of the 515 who had been enrolled a little more
than 16 weeks earlier still remained in the factories and among women 279 out of
385 enrolled were still working in the factories. In the 385 unmatched samples
the number of anaemic women had reduced from 141 before the intervention to 79
after - mean haemoglobin increasing from 12.2 to 13.0 (p < 0.001) and in the 279
paired samples prevalence of anaemia had reduced from 105 to 58 - mean
haemoglobin increasing from 12.1 to 13.0 (p < 0.001). CONCLUSIONS: Our results
demonstrated that in resource poor regions, where prevalence of anaemia is high,
the workplace may be considered an ideal location to give a weekly supervised
dose of iron, folic acid and vitamin C to effectively tackle the problem and
probably improve worker efficiency.
PMID- 24353507
TI - Causes of short stature identified in children presenting at a tertiary care
hospital in Multan Pakistan.
AB - OBJECTIVE: To determine the frequency of common causes of short stature in
children presenting to the Children's Hospital & the Institute of Child Health,
Multan. METHODOLOGY: This cross sectional study was done in Pediatric
Endocrinology department, the Children's Hospital & the Institute of Child
Health, Multan, from March to September, 2011. One hundred and sixty nine
children with short stature presenting to the outpatient department meeting
inclusion criteria were recruited after taking an informed consent. The detailed
history, physical examination including anthropometric measurements and relevant
investigations were recorded. Causes of short stature (outcome variable) were
recorded on a predesigned proforma for final analysis. RESULTS: The common causes
of short stature identified were; familial short stature (FSS) 36 cases (21.3%),
hypothyroidism 29(17.2%), growth hormone deficiency (GHD) 18(10.7%), insulin
dependent diabetes mellitus (IDDM) 16(9.5%) and constitutional delayed growth and
maturation (CDGM) 11(6.5%) cases. This was followed by primary malnutrition
8(4.7%), celiac disease 6(3.6%),Turner syndrome 5(3%) cases and unknown syndromes
4(2.4%) followed by other rare causes. CONCLUSION: Common causes of short stature
identified in this study were endocrine diseases followed by normal variant short
stature (NVSS), while nonendocrine causes were the least.
PMID- 24353508
TI - Management of thoracic trauma in emergency service: Analysis of 1139 cases.
AB - OBJECTIVE: Thoracic trauma is a common cause of significant morbidity and
mortality. This study presents a series of thoracic trauma with the aim to assess
epidemiologic features, distribution of pathologies, additional systemic
injuries, diagnosis, management and outcome. METHODOLOGY: Between January 2007
and December 2011, all patients with thorax trauma admitted to the emergency
service of our hospital were retrospectively reviewed with respect to age,
gender, etiological factors, distribution of pathologies, additional systemic
injuries, diagnosis, treatment modalities, referral and outcome. RESULTS: A total
of 1139 patients with thorax trauma were included in the study. Of these, 698
(61.3%) were male and 441 (38.7%) were female, and the average age was 54.17+/
17.39 years. 1090 (95.7%) of the patients had blunt trauma, whereas 49 (4.3%) had
penetrating trauma. Etiological factors were falls in 792 (69.5%), motor vehicle
accidents in 259 (22.8%), animal related accidents in 39 (3.4%) and penetrating
injuries in 49 (4.2%) patients. It was found that 229 (20%) patients had single,
101 (8.9%) had double, 5 (3%) had three or more, 10 (0.9%) had bilateral rib
fractures and 19 (1.7%) had sternal fracture. Pneumothorax was diagnosed in 58
(5.1%) patients, whereas hemothorax, hemopneuomothorax and other system injuries
were diagnosed in 36 (3.2%), 38(3.3%) and 292 (25.6%) respectively. In our
series, thirteen patients (mortality rate 1.1%) died as result of hemorrhagic
shock (n=8), respiratory distress (n=3) and severe multiple trauma (n=2).
CONCLUSION: Although majority of the patients with thorax trauma receive
treatment as outpatients; thoracic traumas may be a life threatening condition,
and should be identified and treated immediately. Mortality varies based on
etiological factors, additional systemic pathologies, capabilities of the
hospital especially diagnostic and treatment facilities in emergency services. We
believe that a multidisciplinary approach to the patients with severe thorax
trauma, and the opportunities of emergency bedside thoracotomy in emergency
services will significantly reduce the morbidity and mortality.
PMID- 24353509
TI - The delayed management of main arterial injuries in extremity trauma: Surgical
challenges and outcomes.
AB - OBJECTIVE: To analyse the early outcome of main arterial injuries with delayed
treatment in extremity trauma and help vascular surgeons in determining proper
treatment strategy for such injuries. METHODOLOGY: Forty-three patients with
delayed treatment of main arterial injuries during May 2003 and January 2008 were
reviewed retrospectively. RESULTS: In 43 patients, injuries were caused by blunt
trauma in 26 cases and penetrating trauma in 17 cases. The maximum ischaemia time
was 38 hours and the minimum was 13 hours. Eight patients underwent primary
amputations and four patients underwent secondary amputation. There was no
perioperative mortality, while wound infection occurred in five patients,
followed by graft occlusion in four patients, arteriovenous fistulae in two
patients and pseudoaneurysm in one patient. CONCLUSION: The delayed intervention
in main arterial injuries is associated with higher risk of amputation, while the
suitable surgical techniques may decrease the risk of limb loss. Viable limbs
should be revascularized in otherwise stable patients even with long periods of
ischaemia.
PMID- 24353510
TI - Comparison of stool antigen test with gastric biopsy for the detection of
Helicobacter Pylori infection.
AB - OBJECTIVE: Helicobacter Pylori (H.pylori) is one of the most important causes of
dyspepsia and diagnosis can be made by invasive or non-invasive methods. One of
the non-invasive methods, H.pylori stool antigen test (HpSA) is simple, fast and
relatively inexpensive. According to this view with regard to gastric biopsy as a
gold standard the sensitivity, specificity, positive and negative predictive
values of this method were calculated. METHODOLOGY: Stool samples of 61 patients
who underwent upper endoscopy and gastric biopsy due to dyspepsia were evaluated
for H. Pylori stool antigen using sandwich ELISA method. RESULTS: From the 61
patients who participated in this study, H.pylori was diagnosed in 38 (62.3%)
gastric biopsies, 25(66%) of these had positive HpSA test. Also, of 27 (37.7%)
positive HpSA cases, H.pylori was seen in 25 gastric biopsies. For this method,
sensitivity of 66% with 93% positive predictive value was calculated. Also, 91%
specificity with 62% negative predictive value was estimated. CONCLUSION: High
positive HpSA indicates high risk of H.pylori infection and high specificity
shows that the likelihood of false positive is low. Therefore, physicians can
trust on this method and start patient's treatment.
PMID- 24353511
TI - Endometrial Stromal Sarcomas: A clinico-pathological analysis of 27 patients.
AB - OBJECTIVE: To evaluate clinico-pathological features and prognostic valuses of
Endometrial stromal sarcomas (ESS) through comparison of the two grade groups
(low- and high-grade disease). METHODOLOGY: We retrospectively analyzed the
medical records of 27 patients who were diagnosed with ESS at a single institute
between March 1988 and November 2009. Our retrospective chart review was approved
by our local institutional Review Board (IRB). RESULTS: The median age of the
patients was 44.0 years, the median follow-up period was 101.0 months and the 10
year survival rate was 74.2%. The median uterine weight was 215.0 gm. Twenty
three (70.4%) and four patients (29.6%) had low- and high-grade disease,
respectively. As primary treatment, twenty-four (70.4%) and three patients
(11.1%) underwent type I hysterectomy and type III hysterectomy, respectively.
Total six cases were recurred and two cases of the six-recurred patients were
distant metastasis (lung) and four cases were died of the disease. Univariate
analysis revealed that the histologic grade and the uterine tumor weight were
significantly related with longer disease-free survival (p=0.025 and 0.043
respectively). CONCLUSION: ESSs with high-grade or larger tumor size have to be
carefully and sufficiently managed, because of its rarity and aggressive
behavior. To determine the proper adjuvant treatment of ESS with high risks,
further clinical data should be collected and studied.
PMID- 24353513
TI - Current pattern of antibiotic resistance of clinical isolates among conjunctival
swabs.
AB - OBJECTIVES: To identify the etiological agent in bacterial conjunctivitis and to
determine the antibiogram of bacterial isolates. METHODOLOGY: This observational
study was conducted at Dr. Essa's Laboratory over a period of 12 months ending in
March 2012. Two hundred samples taken from conjunctiva of patients with
conjunctivitis were cultured on routine medium and the antibiograms of bacterial
isolates were determined by Kirby- Bauer disc diffusion method. RESULTS: The
analysis of the culture showed that 41% were cultured positive with gram positive
bacteria Staphylococcus aureus 52.5% and Staphylococcus epidermidis 30.1% and
Micrococci 8.3%. However, 9.1% were gram negatives with Klebsiella pneumoniae
5.14% and Pseudomonas aeruginosa 2.6% and 1.36% were others (Acinetobacter,
Haemophilus , E.coli and Moraxella) keeping in view the increasing use of contact
lens and unclean fingers. The overall antibiograms of bacterial isolates indicate
aminoglycosides (gentamicin, tobramicin) and the newer quinolones as apparent
drug of choice for empirical therapy, followed by chloramphenicol, since drug
fussy gram-negatives such as Pseudomonas, Acinetobacter and E.coli were among the
conjunctival isolates. Resistance profile of gram positive isolates shows
cefixime 91.4%, doxycycline 57.9%, cotrimoxazole 29.3%, ampicillin 22.9%,
ciprofloxacin 13.4%, cephradine 8.3%, cefuroxime 7.1%, fosfomycin 4.7%,
ceftriaxone 3.6%, co-amoxiclav 3.6%, cefotaxime 3.5%, vancomycin 2.6%.
CONCLUSION: Resistance to all conventionally used antibiotics is increasing,
therefore identification of etiological agent and antibiogram is important to
treat conjunctivitis and to avoid complications.
PMID- 24353512
TI - To differentiate benign from malignant thyroid nodule comparison of sonography
with FNAC findings.
AB - OBJECTIVES: To evaluate the diagnostic accuracy of sonography and Fine Needle
Aspiration Cytology (FNAC). METHODOLOGY: This follow-up study was approved by
review board and conducted at Endocrine Clinic and Radiology Department of Imam
Reza, Kermanshah. The patients were diagnosed to have thyroid nodule examined by
FNA and Sonography suspicious malignant cases underwent surgery. RESULTS were
entered in SPSS 11.5 chi-Square and Fisher exact test applied to compare
malignant and benign nodule characters. RESULTS: In this study 144 patients were
examined and 14 cases (9.7%) had malignant nodule. Most of malignant nodules were
single (p=0.001), solid (p < 0.001), hypo-echo (p=0.001), with irregular margins
(p < 0.001) and with calcification (p=0.041). There was no significant
relationship between malignancy and nodule size of larger than 15 mm (p=0.395).
Compared with surgery, FNA sensitivity and specificity were calculated as 92.8%
and 100% respectively. CONCLUSION: Based on the result of this study, thyroid
nodule size must not be considered as a criterion for malignancy and thyroid
nodules of any size must be suspected as malignant. Important criteria for
malignancy include irregular edges, being solid, hypoechogenicity and being a
single nodule respectively. Compared with Surgery, FNA Sensitivity and
specificity were calculated as 92.8% and 100% respectively.
PMID- 24353514
TI - Changing pattern of infective endocarditis in Iran: A 16 years survey.
AB - OBJECTIVES: To investigate the changes in characteristics of patients with
infective endocarditis in Iran and comparing the results with the changing
profiles of Infection Endocarditis (IE) in other countries. METHODOLOGY: We
studied all patients with definite or possible IE seen at four referral teaching
hospitals in Iran from Jan. 1995 to Dec. 2010. The data was analyzed both
collectively and separately in two consecutive eight-year periods, i.e. 1995-2003
and 2004-2010. RESULTS: A total of 286 episodes of IE, 172 males and 114 females,
were reviewed from which 162 ones were in the first eight-year time period and
124 episodes in the second one. Mean age of the patients was significantly
increased in the second eight-year period (24.2+/-11 vs 39.4+/-15 years old, p
value = 0.01). Increase in the episodes caused by Staphylococcus aureus was
significant (40.7% vs 22.8%, p value = 0.01). The mean size of the vegetation was
noticeably higher among IDUs than non-IDUs (1.53+/-0.1cm vs 0.76+/-0.2cm, p value
< 0.001). As well as extra cardiac complications, mortality rate was noticeably
higher among the patients with vegetation size >= 1cm (34.4% vs 16.3%, p value =
0.003). There was not a significant difference regarding the mortality rate
between the conservatively and surgically treated patients (20.7% vs 22.9%, p
value = 0.07). CONCLUSION: The most important changing characteristic of IE which
influences the outcome of the disease seems to be vegetation size which can
account for as the outcome predictor.
PMID- 24353515
TI - Risk factors for coronary heart disease in patients below 45 years of age.
AB - OBJECTIVE: To examine the traditional risk factors and biochemical profile of
patients with established CAD (coronary artery disease), and compare the trends
of these in specified age groups of different populations as depicted in various
studies. METHODOLOGY: All consecutive patients below 45 years of age, having
classical history of Ischemic heart disease and also having definite ECG changes
consistent with coronary artery disease were enrolled. These patients were
admitted to CCU/Intermediate Coronary Care Unit of Pakistan Ordinance Factories
(POF) Hospital Wah Cantonment from April 2007 to December 2011. Patients who had
doubtful history as regards CHD and those having ECG changes not classically
consistent with CAD were excluded. Information collected through Performa
included history including family history and details of risk factors. Clinical
examination was carried out and relevant investigations including the serial ECG
changes were recorded. Blood samples were collected after an overnight fast of 14
hours and tests were done for total cholesterol and HDL cholesterol by using
Pioneer-USA, linear chemical kits by cholesterol oxidase and enzymatic calometric
method. RESULTS: A total of 109 cases were included. Cigarette smoking (46%)
Family history (43%), Hypertension (37%), Dyslipidemia (33%), Diabetes mellitus
(18%) and above normal BMI (63.3%) are the most common risk factors in our
patients. Increased abdominal girth has appeared to be an important risk factor
and at occasions is documented to be independent of obesity. Casual dietary
habits and sedentary life style are the other less important risk factors. The
majority of risk factors were equally prevalent in males as well as females
except smoking which was less prevalent in females. CONCLUSIONS: Our study shows
that Family history, Smoking, Hypertension, increased BMI, increased Abdominal
girth, Dyslipidemia and Diabetes Mellitus are the main risk factors. Considering
the increasing incidence of the coronary heart disease in our society it is
essential to assess and evaluate these risk factors at national level.
PMID- 24353516
TI - Evaluation of Aspirin and Clopidogrel resistance in patients with Acute Coronary
Syndrome by using Adenosine Diposphate Test and Aspirin Test.
AB - OBJECTIVES: To evaluate Aspirin and Clopidogrel resistance/non-responders in
patients with acute coronary syndrome (ACS) by using adenosine diposphate and
aspirin tests. METHODOLOGY: In the study patients with ACS loaded with 300 mg of
clopidogrel and 300 mg aspirin and patients on stable daily dose of 75 mg of
clopidogrel (more than 3 days) underwent PCI. Response to clopidogrel and Aspirin
was assessed by Adenosine Diphosphate (ADP) Test (20 umol/L) and Aspirin Test
(Acetyl Acid) (ASP) 20 umol/L, respectively, using the Multiplate Platelet
Function Analyzer (Dynabyte Medical, Munich, Germany). RESULTS: Sixty four
patients were included in this study out of which 57 were with ACS and 7
scheduled for percutaneous coronary intervention (PCI) electively. The proportion
of Aspirin good responders and adequate responders were 76.56% and 18.75%,
respectively while adequate response and good response to Clopidogrel accounted
for 29.7 and 48.4%, respectively Hyperlipidaemia was only co-morbidity associated
with higher AUC ADP value (p: 0.046). Hypertriglyceridaemia and serum calcium
were weakly correlated with higher AUC ADP serum calcium r=0.08, triglyceride
r=0.12. Patients admitted for scheduled PCI and on stable dose of 75mg
clopidogrel exhibited lower AUC ADP value as compared to those admitted with
acute coronary syndrome given loading dose of 300mg of Clopidogrel. Post loading
dose measurement of anti-platelet therapy among ACS patients using the Multiplate
Platelet Function Analyzer showed comparable results with other methods.
Conclusions : As determined by Multiplate Platelet Function Analyzer, Aspirin
resistance/non-responders in this study in acute coronary syndrome patients
accounted for 4.69% while Non-responders in Clopidogrel was 21.9%.
PMID- 24353517
TI - Aspiration and methylprednisolone injection to the cavity with IV cannula needle
in the treatment of volar wrist ganglia: New technique.
AB - OBJECTIVE: There are several types of treatment modalities for wrist ganglions.
The aim of the study was to assess the effectiveness of cyst aspiration and
methyl prednisolone acetate injection with double IV cannula rather than sharp
pointed needle, as a new technique in the treatment of volar ganglia.
METHODOLOGY: The study involves total of 19 patients who received treatment by
aspiration and methyl prednisolone injection into the cavity. Two IV cannulas are
pricked to the cystic cavity. Cyst fluid is drained by the distally placed IV
cannula meanwhile injecting methyl prednisolone by proximally placed IV cannula.
The patient records and follow-up reports are retrospectively investigated. The
patient age, sex, site of the cyst, the treatment that was applied, adjacency to
the artery and the nerves and recurrence are recorded. Mean follow up time was
2.1+/-0.5 years. RESULTS: The study involved 19 patients that received aspiration
treatment for volar ganglion cysts between January 2004 and December 2009. There
were 12 (63.2%) female and 7 (36.8%) male subject with volar wrist ganglion cyst.
The mean age of patients was 27.63+/-6.6 years. Fourteen (73.7%) patients of
total had cysts close to the artery. We didn't observe any complication related
to methyl prednisolone injection and arterial ischemia. Recurrence was observed
in three (15.8%) patients. CONCLUSION: This method has lower recurrence rate than
other aspiration therapy with sharp pointed needle. We prefer to use IV cannula
needle for cyst aspiration and steroid injection in treatment of volar ganglia
before any surgical intervention.
PMID- 24353518
TI - The diagnostic evaluation of dual-source CT (DSCT) in the diagnosis of coronary
artery stenoses.
AB - OBJECTIVE: To evaluate the diagnostic accuracy of dual-source computed tomography
(DSCT) in the diagnosis of coronary artery stenoses by comparing with
conventional coronary angiography (CCA). METHODOLOGY: CCA and DSCT were performed
in 64 patients with suspected coronary artery disease (CAD) respectively (46
male, 18 female, age from 48 to 82 years old, mean 68.18 years). Various post
processing reconstructions of coronary artery and its branches, such as
volumetric imaging, multi-planar reconstruction, curved planar reconstruction,
maximum intensity projection were used. The coronary segments, with statistical
evaluations combined with its diameter >=1.5mm were collected to analyze the
diagnosis accuracy of DSCT on coronary artery stenoses, with CCA as the gold
standard. RESULTS: About 4.14% of coronary artery segments could not be
evaluated, while 95.86% were evaluable arteries, the sensitivity, specificity,
positive and negative predictive value of DSCT for detecting coronary artery
stenoses were, 93.58%, 99.61%, 95.31% and 99.48% respectively. There were no
significant differences in the diagnostic accuracy of coronary artery stenoses
between DSCT and CCA. CONCLUSION: DSCT is a reliable tool that is accurately
appropriate for patients with CAD, as it has a higher accuracy and specificity,
which is valuable in the screening of CAD.
PMID- 24353519
TI - Assessment of prophylactic bone grafting effect on union of open tibial fracture.
AB - OBJECTIVE: The fracture of the tibial shaft is the most common fracture of long
bone in human. Considerable proportion of this fractures are open fractures.
Treatment of open fractures is one of the orthopedic problems. In the developing
country with economic problem, early mobilization and returning to work may be
important for people. We compared result of treatment with addition of autogenus
bone graft in two different time periods in two groups. METHODOLOGY: In this
study, 144 patients with open tibial fracture were randomly divided in two groups
and were treated with autogenus bone graft at two different time intervals, the
first group in the end of third week and second group in the end of sixth week.
All Patients were followed up periodically in first two month every month and
then every two weeks. T-test was used for comparison. SPSS ver. 13.0 (SPSS Inc,
Chicago, IL, USA) was used for analysis. RESULTS: The mean fracture healing time
in the first group (with bone graft in 3rd week) was 14.24+/-4.4 week and in the
second group (with bone graft in 6th week) was 16.4+/-5.4 week and the difference
was statistically meaningful. Differences in the rate of delayed union and none
union in two groups were statistically insignificant. In addition to time of bone
graft, the age, gender, injury mechanism, fixation method, cigarette smoking and
drug abuse were studied in two groups. The difference as regards these factors in
two groups was statically insignificant. CONCLUSIONS: Achievement of autogenus
bone graft in open tibial fracture at the end of third week causes reduction of
union time from 16.4 week to 14.4 week without increment of deep infection.
PMID- 24353520
TI - Characteristics and outcome of dengue infection; clinical perspective from a
secondary care hospital of Karachi.
AB - OBJECTIVE: To determine the frequency and characteristics of dengue fever (DF) in
patients of acute febrile illness presenting at a secondary care hospital.
METHODOLOGY: The observational cross sectional study was carried out from May to
October 2010 in Remedial Centre Karachi and included patients above the age of 12
years who presented with acute febrile illness. The WHO classification and case
definitions were used to classify the disease as Dengue Fever (DF), dengue
hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Clinical, hematological
and biochemical findings were recorded serially until discharge. RESULTS: During
the study period, 90 (34.75%) presented with typical features of DF, 28 (31.11%)
were dengue proven, seven (7.7%) proved to be of malaria in which malarial
parasites were found positive in the peripheral blood, while the remaining 55
(61.11%) patients were dengue probable. Age of the patients ranged from 13 to 76
years. Fever was the most common clinical presentation (100%) followed by
vomiting 50 (55.56%), body ache 31 (34.44%) abdominal pain 17 (18.89%) and
headache 9 (10%). Maculopapular rash was seen in 4(4.44%) patients. Laboratory
findings included thrombocytopenia, leucopenia and raised alanine
aminotransferase levels. Eighty one patients (90%) improved clinically and
hematologically and were discharged in stable condition. CONCLUSION: Fever and
thrombocytopenia were the most common presentation of dengue fever (DF). The
overall mortality of DF is low, if treated appropriately. Awareness of health
care professionals and public regarding preventive strategies is essential to
fight against this disease.
PMID- 24353521
TI - Clinical profile of carpal tunnel syndrome in a teaching hospital.
AB - OBJECTIVES: The aim of this study was to review the clinical characteristics and
demography of Carpel Tunnel Syndrome (CTS) cases presented to a university
hospital. METHODOLOGY: A retrospective study was done for 336 consecutive
patients (290 females and 46 males), referred with a clinical diagnosis of CTS to
the Neuro-diagnostic laboratory at King Abdulaziz University Hospital, Jeddah,
Saudi Arabia, between January 2007 and December 2010. All subjects had clinical
evaluation and standardized nerve conduction studies (672 hands) performed by the
same examiner. RESULTS: Carpal tunnel syndrome was confirmed in 640 hands
(95.23%) with female predominance (86.3%). The mean age was 52.4 in females and
54.4 years in males with overall highest occurrence among the age group 45- < 55
years. Bilateral CTS was confirmed in the majority of the patients, i.e.,
304(90.5%), and remaining were unilateral. Among unilateral pattern, 22 (68.8%)
had right CTS and others had left CTS. Most of the patients were treated
conservatively 85.4% while the rest had surgical decompression 14.6%. CONCLUSION:
Overall predominant age group was 45-<55 years with female dominancy. Majority of
subjects had bilateral CTS as well as conservative treatment was frequent.
PMID- 24353522
TI - An evaluation of Milligan-Morgan and Ferguson procedures for haemorrhoidectomy at
Liaquat University Hospital Jamshoro, Hyderabad, Pakistan.
AB - OBJECTIVE: o compare the outcome of Milligan-Morgan (MMH) and Ferguson (FH)
techniques for haemorrhoidectomy with regard to postoperative pain, control of
bleeding, early mobilization of patients and wound healing. METHODOLOGY: In this
prospective, randomized clinical study conducted between January 2005 to December
2008, 213 patients with late 2(nd) degree; third or fourth degree hemorrhoids
were assigned to two groups. One hundred ten patients in group A were operated by
an open method and 103 patients in group B were operated by closed method.
RESULTS: Age ranged from 22-70 years with mean age of 45.5 years. Peak incidence
was between 41-50 years. Out of 213 patients, 170 (79.81%) were male and 43
(20.18%) were females. The mean +/- SD operating time was significantly more in
group B (31.3+/-4.8 min) than group A (25.2+/-5.6). The duration of
hospitalization and duration off from work was more in group A than the group B.
Wound healing was quicker in group B than the group A. Post operative pain scores
were significantly low in the Group A than Group B during first 24 hours and at
first bowel movements. Reactionary hemorrhage occurred in 4 (3.63%) patients of
group A, no patient in group B developed this complication. Retention of urine
was seen in 13 (11.81%) patients in group A and 4 (3.88%) in group B. No patient
in group A developed anal stenosis, while 3 (2.91%) patients in group B developed
anal stenosis. Wound infection was one (0.9%) in group A and two (1.9%) in group
B. Two (3.63%) patients in group A came with recurrent hemorrhoids and in group
B, only one (0.97%) patient reported recurrence. CONCLUSIONS: The closed
technique is more beneficial with respect to postoperative pain, control of
bleeding, early mobilization of patients and wound healing.
PMID- 24353523
TI - Music can effectively reduce pain perception in women rather than men.
AB - OBJECTIVE: Nowadays music is used to decrease pain and increase relaxation in
clinical settings. It is hypothesized that music can affect women more easily
than men. We assessed the effect of two types of music (Iranian folkloric and
preferred music) on pain tolerance and pain rating in cold pressor test.
METHODOLOGY: A consecutive sample of 50 healthy Iranian medical students was
enrolled. They reported pain tolerance and pain rating in cold pressor test in
three different musical conditions served as the outcome measures. The results
were analyzed with repeated measurement analysis of variance. RESULT: Mean
tolerance time was significantly higher in preferred music compared to Iranian
folkloric music (F (1,48) =25.44, p=0.0001) and no music (F(1,48)=3.51, p=0.0001)
conditions. There was a significant interaction when tolerance time in no music
condition was compared to preferred music condition, regarding sex; Tolerance
time increased more in females (F(1,48)=5.53, p=0.023). The results also
indicated that pain ratings, regardless of sex, were different in three musical
conditions (F(1.7,81.34)=15.37, p=0.0001). CONCLUSION: Music distracted attention
from pain and Women can be impressed and distracted more easily by music.
PMID- 24353524
TI - Analysis of subconjunctival hemorrhage.
AB - OBJECTIVE: To determine associated conditions, gender distribution and location
of subconjunctival hemorrhage (SCH). METHODOLOGY: This retrospective,
observational and non-interventional study involved total of 50 patients with SCH
aged 0.16-88 years. The conjunctiva was divided into 4 equal areas. The data
about the subjects with SCH that includes age, gender, medical history, ocular
history and location of hemorrhage were noted for all patients. RESULTS: The
patients with SCH consisted of 21 (42%) women and 29 (58%) men, with a mean age
of 29.56 years. Of the 50 patients, 34 (68%) had traumatic and 16 (32%) had
spontaneous SCH. Of traumatic SCH group 24 (70.6%) were men and 10 (29.4%) were
women. SCH was more common in the temporal areas than other areas (40.5%).
CONCLUSION: The most associated condition in spontaneous SCH was hypertension.
SCH was found to be predominant in the temporal areas among all patients. In
traumatic SCH, temporal areas were affected more, whereas in spontaneous SCH,
nasal and temporal areas were affected equally. Traumatic etiology was more
likely seen in men than women.
PMID- 24353525
TI - Analysis of some common pathogens and their drug resistance to antibiotics.
AB - OBJECTIVE: To investigate the common bacterial resistance of clinical isolates in
our hospital in the second half of 2011. METHODOLOGY: Pathogens isolated from
clinical samples in the second half of 2011 were analyzed and categorized to
perform susceptibility tests. RESULTS: In the gram-negative bacteria,
Enterobacteriaceae and non-fermenting gram-negative bacilli accounted for 55.89%
and 34.51%. In the gram-positive bacteria, Staphylococcus aureus, Coagulase
negative staphylococci, Enterococcus, Strptococcus pneumonia accounted for
32.85%, 40.39%, 12.41% and 10.22%, respectively. Other species accounted for
4.14%. Klebsiella pneumonia and Pseudomonas aeruginosa were sensitive to
cepoperazon, cefepime and imipenem. However,Acinetobacter baumannii was more
sensitive to carbapenems antibiotics, which was followed by fourth generation
cephalosporins. Klebsiella pneumoniae was extremely sensitive to amikacin,
cefepime and imipenem, but was resistant to ampicillin. The detection rates of
the broad-spectrum Escherichia coli, Pseudomonasaeruginosa and Klebsiella
pneumoniae were 54.51%, 52.08% and 38.65%. The gram negative bacilli were the
prevalent clinical pathogens in our hospital in the second half of 2011.
CONCLUSION: The drug resistance of pathogenic bacteria has increased
significantly recently, thus the surveillance of antibacterial agents is
necessary, and rational use of antibiotic will be urgently needed to reduce the
production and dissemination of drug resistant strains.
PMID- 24353526
TI - Effects of blocking of angiotensin system on the prevalence of metabolic syndrome
in type 2 diabetic patients.
AB - OBJECTIVE: To evaluate prevalence of metabolic syndrome in hypertensive type 2
diabetic patients treated with antihypertensive drugs that inhibit renin
angiotensin system. METHODOLOGY: Two groups of patients were included in this
study. The first group involved 130 hypertensive type 2 diabetic patients taking
enalapril, captopril (Converting Enzyme inhibitors), valsartan or telmisartan
(Angiotensin II receptor blockers) as monotherapy whereas group 2 involved 92
type 2 diabetic patients with normal blood pressure. Metabolic syndrome was
diagnosed according to criteria made by the US National Cholesterol Education
Program Adult Treatment Panel III. Serum glucose concentration, serum
triglycerides and HDL-cholesterol were measured by using special kits. RESULTS:
The percentage of patients having metabolic syndrome was lower in group 1
(58.47%) as compared with group 2 (73%). Waist circumferences, triglycerides and
FBS were significantly lower in group 1 as compared with group 2. BP and HDL
cholesterol were significantly higher in group 1 as compared with group 2.
CONCLUSION: Inhibition of RAS by converting enzyme inhibitors or angiotensin II
receptor blockers captopril, enalapril, valsartan or telmisartan produce
beneficial effects on the markers of metabolic syndrome and can reduce the
frequency of metabolic syndrome in type 2 diabetic patients.
PMID- 24353527
TI - Phenotypic characterization of ESBL producing Enterobacter cloacae among
children.
AB - OBJECTIVE: The emergence of ESBL producing Enterobacter cloacae in clinical
isolates is posing a serious threat for treating nosocomial infections. The aim
of the study was to determine the frequency of extended spectrum beta-lactamase
(ESBL) producing Enterobacter cloacae and to compare the phenotypic methods used
for the characterization of ESBL producing strains. METHODOLOGY: This cross
sectional observational study was conducted during April 2011 to March 2012 at
Microbiology department of The Children's Hospital and Institute of Child Health,
Lahore. A total number of 20,257 various clinical samples were analyzed during
the study period. Enterobacter cloacae were identified using API 20E system and
ESBL detection was carried out using double-disk synergy test (DDST) and CLSI
confirmatory test. RESULTS: Enterobacter cloacae were isolated from 221 samples,
out of which 33 (14.93%) were ESBL producers and 188 (85.07%) were non-ESBL
producers. The gender distribution of ESBL producing Enterobacter cloacae was 21
(63.6%) in males and 12 (36.4%) in females. Highest frequency (63%) of ESBL
producing Enterobacter cloacae was detected in blood samples. Comparison of DDST
and CLSI confirmatory test showed that 25 (75.75%) isolates were characterized by
DDST and 33 (100%) using CLSI confirmatory test. CONCLUSION: The present study
shows moderately high frequency of ESBL producing Enterobacter cloacae among
children. DDST was found to be less efficient in ESBL detection as compared to
CLSI confirmatory test.
PMID- 24353528
TI - BAL for pneumonia prevention in tracheostomy patients: A clinical trial study.
AB - OBJECTIVE: To evaluate the role of flexible bronchoscopy (FB) and bronchoalveolar
lavage (BAL) on pneumonia prevention of tracheostomy patients in intensive care
unit. METHODOLOGY: This clinical trial was conducted on 67 head-injury patients
who needed tracheostomy. The eligible patients were divided into two groups of
different methods for removing the airway secretions. In intervention group, FB
and BAL was added to routine conventional methods for airway clearance. Patients
were followed for signs and symptoms of pneumonia. Results : The risk of
nosocomial pneumonia decreased from 35% to 14% in intervention group. The days of
hospital stay were significantly reduced with bronchoscopic method. CONCLUSIONS:
Flexible Bronchoscopy is recommended to all ICU admitted patients that have
tracheostomy tube and high volume of secretion in their airways. It can not only
prevent the pneumonia formation decrease the morbidity and mortality rate but it
can even shorten the ICU stay time and consequently reduce the costs of
treatment.
PMID- 24353529
TI - Role of platelet indices, glycemic control and hs-CRP in pathogenesis of vascular
complications in type-2 diabetic patients.
AB - OBJECTIVES: Alteration in platelet morphology and functions are associated with
pathological processes and increased risk of vascular complications in patients
with diabetes. The purpose of the study was to find the correlation between
platelet indices with fasting blood glucose, HbA1c and hs-CRP level in
pathogenesis of vascular complications in type 2 diabetic patients. METHODOLOGY:
The study has been carried out on 51 Type 2 Diabetics and 55 age and sex matched
healthy control subjects. Fasting blood glucose (FBG), Glycosylated hemoglobin
(HbA1c), high sensitivity C- reactive protein (hs-CRP) level and platelet indices
including Platelet count (PLT), Plateletcrit (PCT), Mean platelet volume (MPV),
Platelet distribution width (PDW) were estimated and compared with normal
subjects. The results were evaluated statistically. RESULTS: The study
demonstrated that FBG, HbA1c, MPV, PDW and hs-CRP were statistically higher in
diabetics in comparison with control subjects (P is less than 0.05). Positive
correlation of FBG with HbA1c (r is equal to 0.993, P is equal to 0.0001), PLT
with PCT (r is equal to 0.922, P is equal to 0.0001) and MPV with PDW (r is equal
to 0.332, P is equal to 0.024) was found in diabetics. CONCLUSION: The poor
glycemic control is positively correlated with high HbA1c level. The increased
values of MPV, PDW and elevated hs-CRP level may also serve as confirmatory test
in finding risk of developing complications.
PMID- 24353530
TI - Effect of colporrhaphy on the Sexual Dysfunction of women with pelvic organ
prolapsed.
AB - OBJECTIVE: To evaluate the effect of colporrhaphy on sexual problems of women
with pelvic organ prolapseis. METHODOLOGY: Sixty patients with pelvic organ
prolapse (cystocele - rectocele) in a quasi-experimental study before and after
treatment were included. Presence of pelvic organ prolapseis was assessed by
examination in the lithotomy position. Degree of prolapse was determined
according to Pelvic organ Prolapse Quantification (POPQ). Their degree of
prolapse was marked from 1 to 3 then was colporrhaphy performed. Follow up of
patients for sexual satisfaction was performed three and six months after surgery
by telephone and interviews. Data were analyzed by SPSS version 15, the McNamara
test, T-test, absolute and relative frequency, mean and standard deviation.
RESULTS: In sixty (60) women who were studied the mean and standard deviation of
pregnancy and delivery rate were 4.4 +/-2.2 and 4+/-2.1 respectively. About 65%
of patients were over 35 years of age, 88.3% of women had the history of vaginal
delivery and 10% of them had both the history of vaginal delivery and cesarean
section. Score of sexual desire abstaining from sex and orgasm due to vaginal
bulge before, 3 months and 6 months after colporrhaphy was significant
(p=0.0001), but of sexual arousal scores there was no differences between each
other. Mean of sexual satisfaction before operation was 30.75+/-5.70 and three
months after operation it was 33.77+/-4.24 and six months after operation 36.03+/
3.5 which according to T-Test there was significant (p=0.0001). CONCLUSION:
Sexual desire, orgasm and sexual satisfaction increased after colporrhaphy,
frequency of intercourse and sexual arousal remains unchanged. It appears that
colporrhaphy reduce symptoms associated with prolapse which is leading to sexual
dissatisfaction and improved sexual satisfaction.
PMID- 24353531
TI - Arterio venous fistula experience at a tertiary care hospital in Pakistan.
AB - OBJECTIVE: To evaluate the two year patency rate of functioning arteriovenous
fistula. METHODOLOGY: This prospective case series study was conducted at
Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, from 1(st)
January 2009 to 31(st) December, 2010. Patients were chosen for CBRC
arteriovenous fistula at wrist and patients undergoing other types of vascular
access or secondary fistula formation were excluded. RESULTS: One hundred and
eighty two patients underwent arteriovenous fistula formation. The mean +/- SD
age was 63 +/- 13 years and there were 102 (56%) males and 80 (44%) females.
12.6% fistulae failed within first month without dialysis. The primary patency
rate was 66.5% at three months and 57.7% at six months. Failing arteriovenous
fistula was managed by new arteriovenous fistula in our series. 28.6% patients
had redo arteriovenous fistula. This study demonstrated a poor outcome for
fistulas in diabetic patients. Fifteen out of 23 (65.2%) who failed primarily
were diabetics and out of these diabetics 13 (86.7%) failed in first three
months. Infection and burst fistulae were found in nine (4.9%), pseudo aneurysm
in 3.2%, fever 4.9%, peri-operative failure 0.55% and burst fistulae 3.2%.
CONCLUSIONS: One-third of radiocephalic fistulas fail within two years. The
outcome is worse for women and diabetic patients. This information may be useful
in assessing and counseling patients with end-stage renal failure. Arteriovenous
fistula is the better and ideal choice for haemodialysis. A Radiocephalic fistula
in forearm seems to have better results as comparison to cubital fossa
arteriovenous fistula. End to side anastomosis results are better than side to
side anastomosis.
PMID- 24353532
TI - Is there a correlation between hs-CRP levels and functional outcome of Ischemic
Stroke?
AB - OBJECTIVE: C-reactive protein, a well known marker of inflammation is being
investigated as a probable marker of predicting acute cardiovascular events and
its severity. The aim of the present study was to assess the possible role of
highly-sensitivity C-reactive protein (hs-CRP) in predicting short-term
functional outcome of ischemic stroke. METHODOLOGY: A prospective study was
conducted on subjects admitted with first attack of confirmed ischemic stroke. It
included 50 male and 52 female. Serum hs-CRP was measured in the 2(nd) (CRP-D2)
and 5(th) days (CRP-D5) post-stroke. Modified Rankin scale (MRS) was measured in
all subjects in the 2(nd) (MRS-D2), 5(th) days (MRS-D5) and also 3 month (MRS-M3)
after stroke to assess the short-term functional outcome and mortality of
subjects. RESULTS: The mean age of the patients was 71.75+/-11.44 years. The
mortality rate was 47.1% in the third months after stroke. There was no
significant correlation between CRP-D2 and MRS-M3 and also between CRP-D5 and MRS
M3 (P>0.05). However there was a significant association between high CRP-D2
(CRP>3) and MRS-M3 and also between high CRP-D5 and MRS-M3 (P<0.005). CONCLUSION:
This study showed that the value of CRP by itself could not predict the severity
of short-term functional disability and it might not be useful as a clinical tool
for predicting outcome.
PMID- 24353534
TI - Spectrum of congenital heart disease in children admitted for cardiac surgery at
Rehman Medical Institute, Peshawar, Pakistan.
AB - OBJECTIVE: To assess age, gender distribution and relative frequency of
congenital heart disease (CHD) in children who underwent palliative or corrective
cardiac surgery at Rehman Medical Institute, Peshawar. METHODOLOGY: This
retrospective study was conducted in Department of Cardiac Surgery at Rehman
Medical Institute (RMI), Peshawar from May 2008 till May 2010. One hundred and
twenty three patients up to age group of 16 years with confirmed diagnosis of
congenital heart disease admitted for Cardiac Surgery at Rehman Medical
Institute, Peshawar were included. RESULTS: Out of 123 patients, there were 71
males (57.7%) and 52 females (42.2%), with male to female ratio of 1.3:1. Sixty
five (52.8%) of the total cases had acyanotic heart defects. Cyanotic heart
defects were seen in 58 patients (47.1%). Ventricular Septal Defect (VSD)
followed by Patent Ductus Arteriosus (PDA) and Atrial Septal Defect (ASD), were
the commonest acyanotic heart lesions, 33.8%, 23.0% and 16.9% respectively.
Tetralogy of Fallot (TOF) was the commonest cyanotic lesion. Conclusion :
Majority of patients with congenital heart disease had acyanotic CHD with the
commonest lesion being VSD. Tetralogy Of Fallot (TOF) was the commonest cyanotic
lesion. Most of the patients were less than five years with no significant
difference in sex distribution. Availability of expertise locally will lead to
more patients getting surgical treatment at an earlier age thereby reducing
morbidity and mortality and improving quality of life for these children.
PMID- 24353535
TI - MRI features of spinal Fluorosis: Results of an endemic community screening.
AB - OBJECTIVES: Fluorosis is endemic in many parts of the world. However community
studies on MRI features of fluorosis are lacking. The aim of this study was to
determine MRI features of spinal changes in a community with endemic fluorosis in
the Thar Desert Pakistan. METHODOLOGY: Randomly selected adults from the Village
Samorindh, district Tharparker, Sindh, Pakistan, with spinal fluorosis diagnosed
on plain x-rays and raised serum fluoride levels were studied from June 2008 to
January 2009. MRI was carried out on 0.5 T open magnet MRI system. Features of
vertebral body, spinal ligaments, intervertebral disc, facet joints, iliac wings
and other incidental findings were noted. Sclerosis was defined as low signal
intensity on both T1 and T2 weighted images. RESULTS were described as mean and
percentage values. RESULTS: All the studied 27 subjects complained of back ache
without neurological signs. The average age was 43.33 +/- 10.45 years; 21 being
male (77.8%). The most frequent findings included generalized vertebral sclerosis
(24, 88.8%), ligamentum flavum hypertrophy (23, 85%), anterior (20, 74%) and
lateral (17, 62.9%) disc herniation, thickened longitudinal ligaments, and
narrowing of spinal foramina. Hemangioma was seen in 04(14.8%). The most commonly
involved level was L1-2, L4-5 and lower dorsal spine. CONCLUSION: Vertebral
sclerosis, a combination of premature degeneration with anterior disc herniation
and an unusually high frequency of vertebral hemangioma formed the spectrum of
MRI findings in subjects with spinal fluorosis having back ache but no
neurological findings.
PMID- 24353533
TI - Justification for hysterectomies and frequency of histopathological lesions of
hysterectomy at a Teaching Hospital in Peshawar, Pakistan.
AB - OBJECTIVE: To determine the justification for hysterectomies and the frequencies
of histopathological lesions and complications in hystrectomised patients.
METHODOLOGY: As a part of a quality assurance process at the Mercy Teaching
Hospital, hysterectomies performed between 1(st) January, 2010 and 1(st) Jan 2012
were retrospectively analyzed for presenting complaints, surgical indication,
histologic findings, and postoperative complications. The hysterectomy was
considered justified if the preoperative diagnosis was verified by the pathology
report or if significant alternate pathology was present. RESULTS: A total of 123
hysterectomies were performed during this period. Eleven (8.9%) patients' results
could not be traced. The other 91.1% had some pathology found. Histologic
findings reconfirmed the clinical diagnoses. The hysterectomies were considered
justified if p=0.000. Hysterectomy was performed abdominally in 88 (71.5%)
patients, vaginally in 35 patients (28.4%). The most common indication for
hysterectomy was fibroid related menorrhagia n=40(32.5%), followed by third
degree uterovaginal prolapse n=30(24.4%), and dysfunctional uterine bleeding
29(23.6%) patients. Fever was the most common 7(5.7%) post operative complication
followed by urinary tract infection 5(4.9%) The incidence of postoperative fever
was greater following abdominal surgery, while urinary tract infection was
greater following vaginal hysterectomy (P=0.370). CONCLUSION: Almost 91.1% of all
hysterectomies in this study were justified. Clinical diagnoses were related to
presenting complaints (p=0.000) and were confirmed by histopathogic findings
(p=0.000). Most of the hysterectomies were carried out abdominally in part
because fewer patients presented with prolapse.
PMID- 24353536
TI - Early and intermediate prognosis of intravenous thrombolytic therapy in acute
ischemic stroke subtypes according to the causative classification of stroke
system.
AB - OBJECTIVES: Intravenous thrombolytic therapy has established acceptable results
in treating ischemic stroke. However, there is little information on treatment
outcome especially in different subtypes. The aim of current study was to
evaluate early and intermediate prognosis in intravenous thrombolytic therapy for
acute ischemic stroke subtypes. METHODOLOGY: Forty eligible patients (57.5% male
with mean age of 63.18+/-13.49 years) with definite ischemic stroke who were
admitted to emergency department of Imam Reza University Hospital, in the first
180 minutes after occurrence received recombinant tissue plasminogen activator.
All investigation findings were recorded and stroke subtypes were determined
according to the Causative Classification of Stroke System. Stroke severity forms
including modified Rankin Scale (mRS) and National Institutes of Health Stroke
Scale (NIHSS) scores were recorded for all patients in first, seven and 90 days
after stroke and disease outcome was evaluated. RESULTS: The etiology of stroke
was large artery atherosclerosis in 20%, cardio-aortic embolism in 45%, small
artery occlusion in 17.5% and undetermined causes in 17.5%. NIHSS and mRS scores
were significantly improved during time (P < 0.001 in both cases). Three months
mortality rate was 25%. Among the etiologies, patients with small artery
occlusion and then cardio-aortic embolism had lower NIHSS score at arrival (P =
0.04). Caplan-meier analysis showed that age, sex and symptom to needle time
could predict disease outcome. CONCLUSION: Intravenous thrombolytic therapy is
accompanied by good early and intermediate outcome in most patients with ischemic
stroke. Small artery occlusion subtype had less disease severity and higher
improvement.
PMID- 24353537
TI - The effects of serum cholesterol, LDL, and HDL levels on gallstone cholesterol
concentration.
AB - OBJECTIVE: Gallbladder stones are common in the Western world, and 70% to 80% of
gallstones are cholesterol stones. This study investigates the effects of serum
cholesterol, LDL, and HDL levels on gallstone cholesterol concentration.
METHODOLOGY: The gallstones of 75 patients with cholelithiasis were examined
using spectrophotometry. RESULTS: High serum cholesterol and LDL levels were
associated with high cholesterol stone rates (86.7% vs. 40.0%, P < 0.001; 75.0%
vs. 48.9%, P < 0.05, respectively). Similarly, high serum cholesterol and LDL
levels were correlated with high gallbladder stone cholesterol concentrations
(63.6% vs. 44.4%, P < 0.001; 62.3% vs. 46.0%, P < 0.001, respectively). In
contrast, low serum HDL levels do not seem to affect the occurrence of
gallbladder cholesterol stones (60.0% vs. 58.3%, respectively, P > 0.05) or
gallbladder stone cholesterol concentrations (50.8% vs. 52.4%, respectively, P >
0.05). CONCLUSION: The relationship between cholesterol, LDL, and HDL levels and
cholesterol gallstone formation is multifactorial and complex and is also
dependent on other individual properties.
PMID- 24353539
TI - Body dysmorphic disorder in aesthetic rhinoplasty candidates.
AB - OBJECTIVE: Body Dysmorphic Disorder (BDD) is a psychiatric disorder defined as
obsessive ideas about distorted physical appearance, leading to social,
professional and personal dysfunction. Many of these patients seek aesthetic
surgery and are generally dissatisfied with the outcome of their surgery. In the
present study patients coming to the otolaryngology clinic of Thaleghani Hospital
in Tehran seeking rhinoplasty were evaluated. METHODOLOGY: Between October 2010
and October 2011, 130 patients seeking rhinoplasty were recruited in a cross
sectional study. These patients were consecutively interviewed in the
otolaryngology clinic of Taleghani Hospital, Tehran, Iran. Questionnaires were
filled containing demographic data. BDD was evaluated by a separate
questionnaire. Hospital Anxiety and Depression Scale (HADS) questionnaire was
filled to evaluate depression and anxiety. Data were analyzed by using SPSS
software. The frequency and standard deviations were calculated. Differences
between groups were evaluated by using the chi-square, and t-tests. RESULTS:
Ninety nine (76.2%) of rhinoplasty candidates were female and thirty one (23.8%)
were male. Eighty five (65.4%) were single and thirty eight (29.2%) were married
while seven were divorced. About 63.8% were University students or University
graduates. Mean age was 26.43+/-6.29 years old. 41 patients (31.5%) had BDD.
Among BDD patients 12 (29.3%) had concurrent depression and 11 (26.8%) had
concurrent anxiety. No statistically significant correlation was found between
the presence or severity of BDD and age, gender, marital status, level of
education and profession. CONCLUSION: Considering the high prevalence of Body
Dysmorphic Disorder (BDD) among rhinoplasty candidates, psychiatric evaluation is
advisable before surgery to avoid unnecessary operations and patient
dissatisfaction.
PMID- 24353538
TI - The management of acetabular malunion with traumatic arthritis by total hip
arthroplasty.
AB - OBJECTIVE: To explore the treatment strategies and clinical effect of the
acetabular malunion with traumatic arthritis by total hip arthroplasty.
METHODOLOGY: A retrospective analysis was conducted on 47 cases of acetabular
malunion with traumatic arthritis from June 2000 to December 2009. All the
patients underwent total hip arthroplasty with bone grafting or titanium cage for
bone defect of the acetabulum. Harris hip scoring system was used for evaluating
the functional recovery of the hip joint. RESULTS: Thirty three cases had an
average of 47 months follow-up. No prosthesis was loosened and the function of
hip joint was improved obviously with the Harris hip scores improving from 43.5
to 87.6. However, there were one case of sciatic nerve injury and four cases of
heterotopic ossification postoperatively. CONCLUSION: Total hip arthroplasty
might be an effective treatment of acetabular malunion with traumatic arthritis.
Proper evaluation and reasonable reconstruction of acetabular defect as well as
reasonable selection of prosthesis are essential to obtain an excellent outcome.
PMID- 24353540
TI - Insulin resistance in non-diabetic patients of chronic Hepatitis C.
AB - OBJECTIVE: To determine insulin resistance in non-diabetic chronic hepatitis C
patients using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
METHODOLOGY: Patients having anti-HCV positive were included in this study.
Patients with diabetes mellitus, thyroid disease, hyperlipidemias,
hypercortisolism and infective diseases other than hepatitis C were excluded.
Age, weight, height and absence of diabetes were documented. Fasting blood
glucose and fasting insulin levels were done. Body mass index and insulin
resistance was calculated using the formulas. Patients having insulin resistance
using formula HOMA-IR>2.5 were labeled as insulin resistant. Data was analyzed
using SPSS-18. RESULTS: One hundred and fifty five patients according to sample
size estimation were enrolled, in whom HOMA-IR was calculated, the mean value was
found to be 2.47 +/-1.30. A total of 79 (51%) of patients had HOMA-IR more than
2.5 showing insulin resistance. CONCLUSION: In a third world country like
Pakistan, where there is a high prevalence of hepatitis C infection, the
consequences of the disease are also very common. Insulin resistance was found in
51% of patients with chronic hepatitis C.
PMID- 24353541
TI - Inconsistency in the strength testing of dental resin-based composites among
researchers.
AB - The aims of this paper were to review the current strength testing methods of the
dental resin-based composites (RBCs) and to explore the inconsistencies with
regard to strength testing among researchers. Data selection/extraction: An
outline of the most relevant aspects of RBCs was created, and a subsequent
literature search for articles published during last four decades (1970-2010) was
conducted using the databases, namely PubMed, Science Direct and ISI Web of
Knowledge. CONCLUSION: The literature review highlighted a lack of consensus
among researchers regarding the reliability of ISO recommended three-point
flexure strength testing method. Several investigators have used Weibull
statistics for the analysis of RBCs strength data, however their applicability
might be questioned as many RBCs contain greater resin content and may exhibit
sufficient viscous deformation prior to brittle failure. In addition, variability
in the selection of cross-head speed and mould material for strength testing was
evident which may lead to variation in the strength data and render the
interpretation difficult among researchers.
PMID- 24353542
TI - Bidirectional Relationship between Chronic Kidney Disease & Periodontal Disease.
AB - Non communicable diseases (NCDs) affect the life of an individual in terms of
mortality, morbidity and financial crises. Main NCDs are diabetes mellitus (DM),
cardiovascular diseases (CVD), pulmonary diseases, osteoporosis and chronic
kidney diseases (CKD). About 40% of the total deaths can be controlled by
eliminating the risk factors for NCDs. Periodontitis have recently been labeled
as an important potential risk factor for NCDs. CKD affect the oral health status
of patients by inducing gingival hyperplasia, xerostomia, calcification of root
canals and delayed eruption of teeth. Periodontitis increases systemic
inflammatory burden leading to worsening of CKD which in turn has been has been
found to negatively affect CKD of patients on hemodialysis therapy by altering
their serum albumin and C-reactive protein levels. As hypoalbuminemia leads to
increased mortality in CKD patients, it needs to be avoided by reducing systemic
inflammatory burden in patients receiving HD therapy. Treating periodontal
disease could be one factor that might decrease the systemic inflammatory burden
and thereby improve quality of life of these patients. SOURCES OF DATA: Data from
descriptive, cross sectional and longitudinal studies published between 2000 and
2012 were included. Data searches based on human studies only. DATA EXTRACTION:
The key words, periodontitis, chronic kidney disease and hemodialysis, on
MEDLINE, approximately 120 studies were identified. 35 of them were relevant to
all three keywords. Most of them were cross sectional studies and total 7
clinical trials were identified regarding checking of serum levels after
periodontal therapy with variable results. CONCLUSION: Patients with CKD have
higher prevalence of periodontal disease while non-surgical periodontal therapy
has been indicated to decrease the systemic inflammatory burden in patients with
CKD specially those undergoing HD therapy.
PMID- 24353543
TI - Acute left main coronary artery occlusion.
AB - The treatment of an acute left main coronary artery occlusion still poses a
challenge. In this case report we present a 50-year-old patient with an acute
occlusion of the left main artery. After a successful angioplasty without
"stenting" due to the complexity of the stenosis the patient underwent a
successful bypass surgery. We discuss the therapeutic options of acute left main
occlusion regarding medical, interventional and surgical options.
PMID- 24353544
TI - A rare case of metachronous triple cancers involving the tympanic membrane.
AB - Multiple primary malignancies are not rare. While metachronous triple cancers are
rare and a triple tumor case involving maxillary sinus and tympanic membrane is
exceptionally rare. We present such an extremely rare case with the index tumor
of adenoid cystic carcinoma of the maxillary sinus and 14 years later esophageal
cancer was observed as a metachronous tumor. One year after esophageal cancer,
squamous cell carcinoma arising from tympanic membrane was detected. Before the
tumor of tympanic membrane was observed, the patient had received total three
radiation courses. Prior radiation therapy is suspected to be playing a role in
inducing the squamous cell carcinoma of the tympanic membrane.
PMID- 24353545
TI - Classic congenital adrenal hyperplasia: A delayed presentation.
AB - Congenital adrenal hyperplasia (CAH) is a rare congenital disorder, which in
cases of female genotype may result in virilization. Specific enzyme deficiencies
in adrenocorticoid hormones biosynthetic pathway lead to excess androgen
production causing virilization. Classic type presents early in infant life as
salt losing or simple virilizing type, whereas non classic form presents late at
puberty or in adult life. Depending on the type of classic CAH, type of
adrenocorticoid deficiency, extent of virilization & genotype, surgical
corrective procedures, glucocorticoid & mineralocorticoid replacement therapy are
the mainstay of management. We present here a case of classic congenital adrenal
hyperplasia of simple virilizing type, which presented later in childhood.
PMID- 24353547
TI - Kawasaki disease in two sets of monozygotic twins: Is the etiology genetic or
environmental?
AB - Two sets of monozygotic (MZ) twins with Kawasaki disease (KD) from two different
families are reported. Twin set 1, previously healthy 71-day-old MZ twin girls
were diagnosed with incomplete KD and pneumonia. The symptoms occurred at the
same time in both girls. Both girls had ectasia of right coronary arteries. In
twin set 2, the younger of 18-month-old MZ twin boys was diagnosed with KD and
bronchitis. After 53 days, his elder brother was diagnosed with the same disease.
The symptoms occurred at different time, but were almost identical. Neither boy
displayed coronary artery changes. These findings support the hypothesis that
genes susceptible to KD and coronary-artery lesions may exist in families. The
different clinical characteristics among MZ twins from different families also
suggest diverse and complex nature of KD.
PMID- 24353546
TI - Irreversible Horner's syndrome diagnosed by aproclonidine test due to benign
thyroid nodule.
AB - We are reporting an irreversible Horner Syndrome (HS) in a patient with benign
thyroid gland nodule in which thyroidectomy was performed for treatment. A 37
year-old female was admitted to our clinic with a swelling in the left lobe of
the thyroid gland and ptosis at the left eyelid. The clinical diagnosis of HS was
confirmed pharmacologically by aproclonidine. Histopathologic examination of
thyroidectomy specimen was reported as benign nodule. To the best of our
knowledge, this is a very rare report in terms of thyroid benign nodule
associated with irreversible HS due to cervical sympathetic chain compression.
PMID- 24353548
TI - A minimally invasive management for abdominal compartment syndrome in severe
acute pancreatitis.
AB - Three patients with severe acute pancreatitis (SAP) developed into overt
abdominal compartment syndrome (ACS) and confirmed or suspected infection of
necrotic tissue. We successfully treated these patients by minimally invasive
decompression with the assist of laparoscope after the failures of intensive care
treatments. This technique we report here may be another safe and effective
management for ACS in SAP.
PMID- 24353549
TI - Meckel Gruber Syndrome: Second trimester diagnosis of a case in a non
consanguineous marriage.
AB - Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder,
incompatible with life. It is characterized by enlarged polycystic kidneys and
post axial polydactyly. Foetal or neonatal death is caused by pulmonary
hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of
gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed
for her current pregnancy at 18 weeks of gestation showed features consistent
with MKS. The termination of pregnancy was declined and a live newborn female was
delivered via an emergency caeserean section at 34 weeks of gestation due to
previous history of lower segment caesarean section (LSCS) & leaking. Physical
examination of the neonate confirmed the features of MKS. The neonate died within
4-5 hours of birth. This case represented a second trimester diagnosis of a
recurrent case of MKS in a non-consanguineous marriage.
PMID- 24353550
TI - Triple synchronous malignant tumors of colon, appendix and liver: A case report
with literature review.
AB - Synchronous cancers are defined as malignant tumors that occur simultaneously.
Each tumor must be primary which eliminate the possibility of being metastatic
lesion of the other. If three separate organs are involved, that is so-called
triple synchronous malignancy with very low morbidity. We report a case of a 33
year old male patient with triple synchronous malignancies at the colon, appendix
and liver.
PMID- 24353551
TI - Traumatic lumbar spondylolisthesis.
AB - Traumatic lumbar spondylolisthesis is a rare lesion and frequently noted in
patients with multiple traumatic injuries. We report one case of L5 traumatic
spondylolisthesis, which obtained successful decompression, reduction, interbody
fusion and fixation by posterior lumbar interbody fusion, and got satisfactory
outcome. We recommend early decompression, reduction, interbody fusion and
fixation with posterior instrumentation to obtain the recovery of neurological
function and stability of the spine.
PMID- 24353552
TI - Proceedings of First International meeting of Research Journal Editors organized
by Islamic World Science Citation Center at Shiraz, Iran (October 23-24(th)
2012).
PMID- 24353553
TI - Hepatocellular carcinoma patients may benefit from left hemi-hepatectomy with
caudate lobectomy.
PMID- 24353554
TI - Gender Discrimination among Medical Students in Pakistan: A Cross Sectional
Survey.
AB - OBJECTIVE: To examine the prevalence and magnitude of gender discrimination
experienced by undergraduate medical students, and its repercussions on their
academic performance and emotional health. METHODOLOGY: A cross sectional study
of 500 medical and dental students studying at a private medical college in
Lahore, Pakistan. RESULTS: Majority (78%) of students reported being victims of
gender discrimination. Females were the main perpetrators (70.8%).Most common
forms were denied opportunities (63%), followed by neglecting students' needs
(44.3%), and unethical talk (43.6%). Most common places of gender discrimination
were teachers' offices (43.7%) and lecture halls (37.2%). Most of the
perpetrators were clerical staff (48%) and professors (43%).Gender discrimination
did not affect the academic performance of most victims (62.6%). The most common
emotional responses were anger (57.6%), frustration (46.7%) and helplessness
(40.3%). 52.4% of students said that gender discrimination still continues and
the majority (83.3%) did not report the problem to college authorities.
CONCLUSIONS: RESULTS demonstrate that gender discrimination is widely prevalent
in undergraduate medical education. Females are both the main victims as well as
the main perpetrators. In most cases gender discrimination does not affect
academic performance but does cause emotional distress.
PMID- 24353555
TI - Patients' receptiveness for Medical students during consultation in Out patient
department of a teaching hospital in Karachi Pakistan.
AB - OBJECTIVE: Patients' attitude towards medical students' presence during treatment
depends on the cultural values of the society. This study was conducted to find
out the patients' receptiveness in our society to be involved in teaching process
for medical students during consultation in out patient department of a teaching
hospital in Karachi Pakistan. METHODOLOGY: This cross sectional study was
conducted in the surgical Out Patient Department (OPD) at Dow University Hospital
from May 2012 to June 2012. Four hundred and eleven patients consented for
participation through non probability purposive sampling, in which 279 patients
were from morning clinics in the presence of students for clinical teaching,
while 132 patients participated through evening clinics of surgery, when students
were not present for comparison in specific dimensions of care for patients'
satisfaction. RESULTS: Majority of patients 293 (71%) agreed with the teaching of
students during consultation and they feel they are contributing in future
doctor's teaching, only 24% patients disagreed. Fifty two percent of patients who
disagreed reported interference in privacy, 34% reported interference in
consultation and 43% felt it resulted in prolong waiting time due to teaching.
CONCLUSION: Majority of the patients agree to be part of teaching for medical
students and this study can be used to assess the educational interventions
designed to improve the patient based teaching.
PMID- 24353556
TI - Evaluation of Continuing Professional Development Program for Family Physicians.
AB - OBJECTIVES: To evaluate the King Saud University Continuing Professional
Development (CPD) Program for Family Physicians in relation to the Convenience,
Relevance, Individualization, Self-Assessment, Interest, Speculation and
Systematic (CRISIS) criteria. METHODOLOGY: A descriptive study was conducted at
King Saud University (KSU) in Riyadh, Saudi Arabia. The authors used the six
strategies of Convenience, Relevance, Individualization, Self-Assessment,
Interest, Speculation and Systematic (CRISIS) for evaluation. The program was
independently analyzed by the three authors using CRISIS framework. The results
were synthesized. The suggestions were discussed and agreed upon and documented.
RESULTS: The results indicate that KSU-CPD program meets the CRISIS criteria for
effective continuing professional development and offers a useful approach to
learning. The course content covers specific areas of practice, but some
shortcomings were found that need to be improved like self assessment area and
individual learning needs analysis. CONCLUSION: This program is suitable for
Family Physicians, as it is well planned and utilizes most of the principles of
CRISIS, but there is still room for improvement. Designing a program for general
practitioners using hybrid model that offers a blend of e-learning as well as
face-to-face learning opportunities would be an ideal solution.
PMID- 24353557
TI - Aetiology, treatment patterns and long-term outcomes of tooth avulsion in
children and adolescents.
AB - OBJECTIVE: Tooth avulsion constituting an emergency for children and adolescents
necessitates management approaches ensuring the survival of avulsed teeth. The
aim of this study was to determine the causes of tooth avulsion and to examine
some factors affecting the clinical & radiographic assessment of their prognosis
after replantation. METHODOLOGY: The study sample was created by using archival
records of patients who were referred to the Suleyman Demirel University, Faculty
of Dentistry, Department of Pedodontics, with complaint of traumatic injuries,
between December 1999 and 2008. The information about age, gender, time and cause
of the injury, number of affected teeth, the root maturation level
(mature/immature), vitality of the affected teeth, condition of supporting
tissues, extra-oral time of avulsed teeth, storage media, time of replantation,
type and duration of splinting, and healing process was obtained from the
patients' records. RESULTS: The sample consisted of 66 traumatized children who
had a total of 93 avulsed anterior permanent teeth. The age of these patients
ranged from 6 to 16 years and the 9- and 10-year-old group had the highest
incidence (n=25). The most frequent causes were falls (n=24; 36.4%). Thirty-three
out of a total of 93 avulsed teeth (35.5%) were replanted. Of the 33 replanted
teeth, 3 (9.1%) were stored in milk and 25 were stored in dry media (n=25;
75.8%). Fifteen teeth (45.5%) were replanted within 30 minutes after the injury.
After clinical and radiographic evaluation a total of 12 replanted teeth (36.4%)
were considered as failed. Ten of the replanted teeth had to be extracted due to
progressive root resorption. Statistical analysis showed no significant
relationship between the successes of replanted teeth with extra-oral period,
storage media, root formation stage, and additional traumas to the supporting
tissues (p>0.05). CONCLUSION: In this study, during the 9-year period, it was
determined that 5.87% of all traumatic dental consisted of avulsion injuries.
Thirty-three avulsed teeth in 26 patients were replanted, and 12 replanted teeth
were revealed as failures. A high rate of success can be obtained when the
avulsed teeth are kept under wet conditions and brought to a dental clinic as
soon as possible.
PMID- 24353558
TI - Clinico-epidemiological nature and antibiotic susceptibility profile of
Acinetobacter species.
AB - OBJECTIVES: Acinetobacter spp. has emerged as an important opportunistic pathogen
responsible for nosocomial infections in many health-care settings worldwide. The
study describes the clinico-epidemiology and antimicrobial susceptibility of
Acinetobacter spp. in a tertiary health-care institution. Methodology :
Acinetobacter spp. were isolated from 141 specimens of the patients who reported
to Universiti Kebangsaan Medical Centre (UKMMC). The sources of specimens were
wound, skin and soft tissue, respiratory and urinary tract from patients in
various wards. Clinio-epidemiological features of patients infected with
Acinetobacter spp. were recorded. Standard bacteriological techniques with API
20NE kits and disk diffusion method were followed for identification and
antibiotic sensitivity of the organisms. RESULTS: One hundred and forty one
patients with positive culture for Acinetobacter spp. were identified. Soft
tissue/wound and respiratory tract were among the commonest sites of
Acinetobacter spp. isolation. The isolates were most frequently obtained from
ICU. All isolates were multi-drug resistant and had a resistance rate of more
than 70% to most antibiotics, except polymyxin B. CONCLUSION: High prevalence of
multi-drug resistance Acinetobacter spp. provides essential information on
judicious antibiotic selection for empirical therapy in our health-care
institution.
PMID- 24353559
TI - Adherence of Healthcare Professionals to American Diabetes Association 2004
guidelines for the care of patients with type 2 diabetes at Peripheral Diabetes
Clinics in Karachi, Pakistan.
AB - OBJECTIVE: To observe the adherence of Healthcare Professionals to American
Diabetes Association (ADA) 2004 guidelines for the care of patients with type 2
diabetes at Peripheral Diabetes Clinics (PDCs) in Karachi, Pakistan. METHODOLOGY:
The study was conducted using a retrospective medical chart review of patients
with type 2 diabetes at four PDCs in four townships of Karachi district from
January 2005 to December 2006. Entire medical records of patients were evaluated
for the evidence of documentation of testing and treatment. RESULTS: Medical
records of 691 patients (332 males and 359 females) with type 2 diabetes were
reviewed. Mean age of the patients was 50.79 +/- 10.75 years. Deficiencies were
observed in most areas of diabetes care. Blood pressure was documented in 85.81%
patients, whereas, serum creatinine, HbA1c and lipid profile were noted in 56%,
44.57% and 40.08% of the patients respectively. Similarly, lower leg examination
was registered in 44% patients, while in 30.53% of the patients fundoscopic
examination was recorded. Co-morbid conditions like hypertension and
hyperlipidemia were documented in 92.7% and 84.6% patients respectively. HbA1c <
7% was achieved by 59.04% patients, while 27.50% of the patients attained the
recommended level of serum cholesterol. Likewise, ADA recommended goal for blood
pressure and LDL was achieved by13.02% and 12.16% patients respectively.
CONCLUSIONS: The study showed that adherence of healthcare professionals to ADA
guidelines was suboptimal. Moreover, insufficient documentation of medical
records reflected inadequate care of patients with type 2 diabetes.
PMID- 24353560
TI - The role of double-balloon enteroscopy following capsule endoscopy in diagnosis
of obscure Small intestinal diseases.
AB - OBJECTIVE: The aim of this study was to evaluate the detection rate accuracy of
Double-balloon Enteroscopy (DBE) after Capsule Endoscopy (CE) in patients with
suspected small bowel diseases. METHODOLOGY: From January 2009 to March 2012,
sixty-two patients with obscure small bowel diseases who underwent CE followed by
DBE were included in this study. Introduction of the endoscope by DBE was either
orally or anally according to CE. RESULTS: Sixty-two patients are reported. The
overall detection rate of small bowel diseases using CE was 70.9% (44/62). Sixty
eight DBE procedures following capsule endoscopy were carried out, There was no
significant difference (chi(2)=0.6739, P>0.05) of Positive findings between CE
and CE +DBE. Furthermore, the detection rate of small bowel diseases in patients
with obscure small intestinal bleeding using CE +DBE (90.9%, 30/33) was superior
to that of CE (78.8%, 26/33); chi(2)=1.8857, P>0.05. CONCLUSIONS: Capsule
Endoscopy (CE) can cover the whole GI tract and provide the selection of the
route of Double-balloon enteroscopy (DBE). DBE can also serve as a good
complementary approach after an initial imaging using CE. It can verify the
findings of CE and provide therapeutic intervention. Using of CE followed by DBE
is effective in the diagnosis and management of patients with obscure small bowel
diseases.
PMID- 24353561
TI - Visceral leishmaniasis: Clinical and demographic features in an African
population.
AB - OBJECTIVE: To describe the clinical and demographic features of patients with
visceral leishmaniasis (VL), from Sudan, Africa. METHODOLOGY: A descriptive study
was conducted during 5 years period on confirmed VL patients. These patients are,
originally, from White Nile Province (WNP) region, a previously non-endemic VL
focus which is located in southern part of Sudan. They were referred during the
period 2006-2010 for management at Tropical Diseases Hospital (TDH) in the
capital Khartoum. The patients data were retrieved from the hospital electronic
software system, and were studied. RESULTS: A total of 71 patients with VL were
reviewed. The main clinical features were: fever 68 (95.8%), splenomegaly 66
(93%), weight loss 61 (85.9%), pallor 59 (83.1%), hepatomegaly 52 (73.2%). The
most notable haematology finding was the mean Hb value (7.6 g/dL) on admission to
hospital. Gender showed males at higher risk for VL as compared to females with a
ratio of 3:1 (53 vs 18). VL was largely a disease of children with 42 (59.1%)
aged < 15 year, and around quarter (23.9%) under 5 years. CONCLUSION: The
clinical features of Sudanese VL in WNP region is, generally, similar to the
pattern seen globally in endemic foci. The majority of the study population are
paediatric indigenous VL patients, suggesting that adults were immune, and
indicating change of disease pattern from previous sporadic to present endemic.
This finding emphasizes the need for research to better understand VL in non
endemic areas with the objective of developing effective and sustainable control
strategies.
PMID- 24353562
TI - Effect of a probiotic preparation (VSL#3) in critically ill patients: A
randomized, double-blind, placebo-controlled trial (Pilot Study).
AB - Objective : Reactive oxygen species (ROS) are a major contributing factor in
diseases pathophysiology in critically ill patients. Oxidative stress usually
occurs in critical illnesses, specifically during sepsis, and organ dysfunction.
The anti-oxidative properties of probiotics may serve as a defense in intestine
and overcome various oxidative stresses. The aim of this trial was to determine
the effect of probiotics on inflammation, antioxidant capacity and lipid
peroxidation in critically ill patients. Methodology : Forty patients admitted to
the intensive care unit were enrolled in this double-blind, randomized controlled
trial. They were randomized to receive placebo or probiotic for 7 days. Serum
levels of Total Antioxidant Capacity (TAC), Malodialdehyde (MDA), C-Reactive
Protein (CRP) and Acute Physiology and Chronic Health Evaluation (APACHE II)
score were measured before initiation of the study and on the 7(th) day. RESULTS:
There was a significant difference in CRP levels and APACHE II score between two
groups at the end of the study (P= 0.003 and 0.001, respectively). There was not
a significant difference in levels of TAC and MDA between two groups.
CONCLUSIONS: Administration of probiotics to critically ill patients caused
reduction in inflammation and improvement of clinical outcome. However, there
were not significant changes in markers of oxidative stress.
PMID- 24353563
TI - Carotid Artery Intima Media Thickness and HsCRP; Predictors for Atherosclerosis
in Prediabetic Patients?
AB - OBJECTIVE: We aimed to assess carotid intima media thickness (CIMT) and serum
high-sensitivity C-reactive protein (hs-CRP) levels as estimated markers of
subclinical atherosclerosis and inflammation in prediabetic patients.
METHODOLOGY: One hundred and ten patients were defined as prediabetic and seventy
six subjects (age and sex matched) were assigned as control group in our cross
sectional study. Bilateral CIMT measurements and hs-CRP levels were evaluated.
RESULTS: The prevalance of hypertension, hyperlipidemia, angiotensin receptor
blockers and antihyperlipidemic medication use were statistically higher in the
prediabetic group. Serum hs-CRP levels, left, right and maximum CIMT were
statistically higher among prediabetics compared to control group. There was a
positive, significant correlation between left, right, maximum CIMT and fasting
blood glucose, HbA1c, hs-CRP levels and BMI. CONCLUSION: Recognising and focusing
on the intervention of prediabetic state as early as possible and identifying the
susceptible patients who may benefit from more aggressive preventive therapy is
an important issue of primary prevention of diabetes and cardiovascular diseases.
PMID- 24353564
TI - Effects of a mat pilates program on cardiometabolic parameters in elderly women.
AB - OBJECTIVE: This study aimed to determine the effects of mat Pilates on resting
heart rate, resting blood pressure and fasting blood glucose, cholesterol and
triglycerides in elderly women. METHODOLOGY: Fifty sedentary, apparently healthy
females aged 60 and older were randomly assigned into a control (CG, n = 25) or
an intervention (IG, n = 25) group. The IG took part in an eight-week progressive
mat Pilates exercise program, three times weekly while the CG did not take part
in any structured exercises throughout the eight-week period. All subjects
underwent pre- and post-tests in which cardiometabolic parameters were assessed.
RESULTS: In the eight-week mat Pilates program, the IG only demonstrated a
significant (p <= 0.05) decrease in systolic BP (p = 0.040) from 135.84 +/-
14.66mmHg to 128.80 +/- 16.36mmHg and a significant increase in blood glucose (p
= 0.000) from 5.07 +/- 0.46mmol.L(-1) to 5.83 +/- 0.57mmol.L(-1), whereas resting
HR (p = 0.148) (from 68.80 +/- 12.58beats.min(-1) to 73.20 +/- 11.46beats.min(
1)), resting diastolic BP (p = 0.342) (from 75.64 +/- 10.10mmHg to 77.44 +/-
9.32mmHg), blood TC (p = 0.073) (from 5.37 +/- 0.99mmol.L(-1) to 5.67 +/-
1.04mmol.L(-1)) and blood TG (p = 0.384) (from 1.77 +/- 0.88mmol.L(-1) to 1.92 +/
0.87mmol.L(-1)) did not produce any significant changes. CONCLUSION: Due to the
contradictory nature of the cardiometabolic variables (except systolic BP) with
the findings of previous studies, it is difficult to establish a case for using
Pilates as a substitute for more conventional forms of exercising when
exclusively attempting to favourably alter cardiometabolic parameters at least
among the elderly women in our sample.
PMID- 24353565
TI - Seroprevalence and risk factors for hepatitis C virus (HCV) infection in pregnant
women attending public sector tertiary care hospital in Hyderabad Sindh.
AB - BACKGROUND AND OBJECTIVES: Pakistan is among the countries having high prevalence
of HCV infection in the population but there is dearth of proper epidemiological
data regarding acquisition of HCV infection in the pregnant population. Our
objective was to determine the seroprevalence of HCV antibodies in healthy
pregnant women and to assess the potential risk factors for HCV infection in HCV
positive subjects and in the control group. METHODOLOGY: This cross sectional and
comparative study was conducted from 1(st) January to 31(st) December 2010 in the
Department of Obstetrics/Gynaecology Unit-I, Liaquat University Hospital
Hyderabad. Sera were collected from all admitted pregnant women and tested for
HCV anti bodies using Elisa kits (Abbott, USA). Data were analyzed using SPSS
version 16.0 statistical package. RESULTS: The seroprevalence of HCV among
pregnant population was found to be 4.7%. HCV positive women were more likely to
have a history of blood transfusion (OR 1.99, 95% CI 1.26- 3.12), History of
therapeutic injection use (OR 2.46, 95% CI 1.43-4.26), history of surgery (OR
1.72, 95% CI 1.12-2.66) and history of sharing household products (OR 1.81, 95%
CI 1.14-2.87). CONCLUSION: HCV seropositive pregnant women were more likely to
have a history of blood transfusion, therapeutic injection use, surgery and
sharing household items.
PMID- 24353566
TI - Anesthetic management of conjoined twins undergoing one-stage surgical
separation: A single center experience.
AB - OBJECTIVE: To summarize our experience in the anesthetic management of conjoined
twins undergoing one-stage surgical separation. METHODOLOGY: Medical records of
conjoined twins admitted to our hospital for treatment and considered for
surgical separation from 1996 to present were retrospectively reviewed. Four
cases of conjoined twins underwent one-stage surgical separation under general
anesthesia. Preoperative evaluation was performed to determine the extent of
anatomical conjunction and associated anomalies. Anesthesia was simultaneously
induced in all conjoined twins. The intubation procedure was successfully
performed with the head slightly rotated to each baby's side, followed by the
administration of vecuronium. Anesthetic agents were administered according to
the estimated weight of each baby. One case of conjoined twins underwent surgical
separation with cardiopulmonary bypass due to shared hearts. Results : All
conjoined twins were successfully separated. No significant respiratory or
cardiac events occurred during surgery except for one twin, which died after
separation because of complicated congenital heart disease. Conclusions :
Accurate preoperative evaluation, respiratory and circulatory management, and
close cooperation of the multidisciplinary team are important aspects of
anesthetic management of conjoined twins surgery.
PMID- 24353567
TI - Comparison between intrathecal and intravenous betamethasone for post-operative
pain following cesarean section: a randomized clinical trial.
AB - OBJECTIVE: Inadequate postoperative pain relief after cesarean section can
increase complications. In this study, we evaluated the effect of intrathecal
betamethasone as an adjunct to bupivacaine on postoperative pain in patients
undergoing cesarean section. METHODOLOGY: Ninety-nine patients undergoing
cesarean section were assigned to one of three groups. Group 1 (Control) patients
received intrathecal bupivacaine, Group 2 patients received intrathecal
bupivacaine plus preservative free betamethasone and Group 3 patients received
betamethasone intravenously with intrathecal bupivacaine. After surgery,
diclofenac in suppository form was administered as needed for analgesia.
Postoperative diclofenac requirements, time to first analgesic administration and
visual analogue scale pain scores were recorded by a blinded observer. RESULTS:
Supplemental analgesic dose requirement with diclofenac for the first 24 hours
were significantly less in both groups that received betamethasone compared to
the control group (P <0.0001). The mean duration of postoperative analgesia was
336.8+/-86 min in Intrathecal group and 312.4+/-106 min in Intravenous group
compared with 245.4+/-93 min in control group (P =0.001). Visual analogue scale
scores were significantly less at 4 hours (P<0.0001) and 6 hours (P<0.0001) after
surgery in groups that received betamethasone in comparison to control group. The
pain scores at 6 hours after surgery were higher in the Intravenous group
compared with the Intrathecal group (P = 0.001); However visual analogue scale
was not different at 12 and 24 hours after surgery between groups (p > 0.05).
CONCLUSION: Intrathecal betamethasone reduced pain and decreased the required
dose of diclofenac in 24 hours after cesarean section.
PMID- 24353568
TI - Efficacy of topical bevacizumab in high-risk corneal transplant survival.
AB - OBJECTIVE: To evaluate the effectiveness of topical Bevacizumab in preventing
neovascularisation on high risk corneal grafts. METHODOLOGY: This study was a
randomized, controlled, parallel group study, carried out from February 2008 to
April 2012 (51 months) at Isra Postgraduate Institute of Ophthalmology and Yasin
eye hospital, Karachi. Eyes with high risk corneal transplantation with corneal
neovascularization were included in this interventional study/randomized clinical
trial. Patients were randomly allocated to 2 groups. Group A and Group B. After
penetrating keratoplasty, group A patients received topical bevacizumab (2.5%, 25
mg/ml) which was self-administered 4 times a day for 24 week while group B
patients received only sham eye drops. Group B was the control group. Corneal
neovascular invasion area i.e. the fraction of area on transplanted cornea in
which vessels were present was measured using mathematical software program
MatLab. Data analyses was done using SPSS version 19. Frequencies of age gender
and groups were measured. Neovascular invasion area and change in visual acuity
was compared between the 2 groups using paired t test . P value of less than 0.05
was considered significant. RESULTS: Among the 2 groups mean Corneal neo vascular
invasion area was minimum in group A (6.23%) while in group B it was (26.7%).
Maximum number of patients (26) attained visual acuity of 6/36 or better in the
topical bevacizumab group compared to 17 sham group. CONCLUSION: When topical
Bevacizumab is used, it reduces the recurrence of neovascularisation and thus
helps increasing the frequency of graft survival in cases of high risk corneal
transplants.
PMID- 24353570
TI - Frequency of migraine in patients with allergic rhinitis.
AB - OBJECTIVES: Allergic rhinitis (AR) is an IgE mediated disease which is released
by activation of mast cells and basophils, and often leads to sinus headache.
Histamine which is the key mediator in the pathogenesis of AR, also plays an
important role in the pathogenesis of migraine with nitric oxide (NO). Aim of our
study was to investigate the frequency of migraine in patients with AR.
METHODOLOGY: Headache assessment and neurological examination was performed on
patients diagnosed as AR in the outpatient ear nose and throat clinic with age
matched controls. Participants with headache were classified according to the
International Headache Society criteria, and migraine frequency was investigated
in the patients with AR and control groups. RESULTS: Migraine headache was
detected in 50% of the patients with AR. Among these, 95% were migraine without
aura, and 5% were migraine with aura. Migraine frequency in the control group was
18.75% in the control group, and all was migraine without aura. Migraine
frequency in the patients with AR was four times higher when compared with the
control group. CONCLUSION: While a histamine and IgE associated common mechanism
is responsible in the pathogenesis of AR and migraine, not only sinus headache
but also migraine headache should be kept in mind. Headache assessment of the
patients with AR, and in case of headache existence, referral of these patients
to neurology outpatient clinics for differential diagnosis and, to maintain
appropriate therapy should not be forgotten.
PMID- 24353569
TI - Yield of esophagogastroduodenoscopy and colonoscopy in cancer of unknown primary.
AB - OBJECTIVES: Carcinoma of unknown primary origin (CUP) is heterogeneous group of
cancers. Role of gastrointestinal (GI) endoscopy in this entity is under
investigated. Aim of this study was to evaluate yield of Colonoscopy and
Esophagogastroduodenoscopy (EGD) in localizing primary tumor in patients with
CUP. METHODOLOGY: Patients with histopathologically proven CUP who underwent
colonoscopy / EGD to find the primary tumor from December 2009 to December 2011
were included in the study. Abdominal symptoms and cytokeratin (CK) 7 and 20
markers were correlated with presence of primary in GI tract. RESULTS: After
giving informed consent 86 patients were included in final analysis. All patients
underwent colonoscopy while 60(70%) got EGD along with colonoscopy. Mean age was
55.10 +/-11.94 years with 52(60%) male. Abdominal symptoms were present in 50%.
CK7+/CK20- in 34(40%); CK7-/CK20+ in 2(2%) while CK7+/20+ in 7(8%) of metastatic
tumor samples. Liver was metastatic site in 47(55%), Lymph node 12(14%) and
Ascites in 8(9%). Endoscopy detected primary in 6 (7%) patients with 3 each in
stomach and colon. No association of abdominal symptoms and cytokeratin markers
was found with presence of GI primary site. CONCLUSION: Yield of localizing
primary lesion in the GI tract by pan-endoscopy was limited. Abdominal symptoms
and cytokeratin markers do not predict presence of gastrointestinal malignancies.
PMID- 24353571
TI - Comparison of Volar and Dorsal approaches for surgical treatment in fracture of
proximal half of the radius.
AB - OBJECTIVE: Fracture of the proximal half of the radius shaft can be exposed by
either one of volar or dorsal approaches. The aim of this study was to compare
the results of volar and dorsal approach for surgical treatment of proximal half
fracture of the radius. METHODOLOGY: This prospective study was performed from
April 2008 to March 2012 in two teaching hospitals. Seventy adults patients with
closed fracture in proximal half of the radius or radius and ulna were operated
on and fixed using small plate and screw by volar approach (VA) (39 patients) and
dorsal approach (DA) (31 patients). Comparison of the results in both surgical
approach were the primary measurement outcome. Duration and time of procedure,
rate and time of fracture union and motion of the forearm were assessed at 4
months after operation. RESULTS: Mean age of the patients with VA and DA was 25.3
and 26.5 years respectively. There was 26 male and 13 female in VD and 22 male
and 9 female in DA patients. Radial nerve injury in VA and DA occurred in three
and two patients, infection in one and nonunion in one other patient was seen in
each group. There was no significant difference in duration of procedure or time
of union after both approaches =0.643. Mean rotation of forearm was 135 deg. in
VA, and 138 deg. in DA patients at 4 months post surgery. CONCLUSION: There was
no significant difference in term of fracture union, early complications, and
range of forearm rotation between volar and dorsal approach for the fixation of
radius fractures in its proximal half.
PMID- 24353572
TI - Risk factors of retinopathy in type 2 diabetes mellitus at a tertiary care
hospital, Bahawalpur Pakistan.
AB - OBJECTIVES: To find out the risk factors of diabetic retinopathy in type 2
diabetes mellitus. METHODOLOGY: It was a cross-sectional study involving 300
patients of type 2 diabetes. Clinical history, relevant examination including
fundoscopy and lab investigations were done. Data was analysed with SPSS 17.0. T
test and chi square/Fischer exact were applied to determine significance.
RESULTS: Mean age of the patients was 49.04 +/- 0.69 years with slight female
predominance with male to female ratio of 3:4. Average duration of disease was
7.17 +/- 0.38 years. Diabetic retinopathy was diagnosed in (74, 23.9%). Mean
HbA1c was 8.15% in patients with retinopathy and 8.884% in those who had no
retinopathy (p=0.08). However, duration of DM, age of patients, male gender, high
total cholesterol, high LDL and microalbuminuria were significantly associated
with the development of retinopathy. CONCLUSIONS: Diabetic retinopathy was found
in 23.9% of type 2 diabetics. It was associated with duration of disease, age at
presentation, male gender, high total cholesterol, high LDL and microalbuminuria.
A single high level of HbA1c was not associated with retinopathy.
PMID- 24353573
TI - Rapid emergence of ESBL producers in E. coli causing urinary and wound infections
in Pakistan.
AB - OBJECTIVES: Production of extended spectrum beta -lactamases (ESBLs) by clinical
isolates of pathogenic E. coli is a very serious therapeutic threat. This study
was aimed to investigate the prevalence of ESBLs and associated drug resistance
in E. coli isolates from urine and pus, and to report the drift from 2005 to 2009
10. METHODOLOGY: Among 173 E. coli isolates, 82 were phenotypically detected as
ESBL producers by standard cefotaxime / clavulanic acid and ceftazidime /
clavulanic acid disc diffusion tests. Antimicrobial resistance of all ESBL
producers was assessed by disc diffusion method. Presence of CTX-M, TEM, SHV and
OXA groups was investigated by PCR. RESULTS: The prevalence of ESBL producing E.
coli increased significantly from 33.7% in 2005 to 60.0% in 2009-10 (urine: 31.8%
to 62.9%; pus: 41.1% to 55.5%). Resistance to cefotaxime, ceftazidime,
ciprofloxacin, gentamicin, nalidixic acid, ticarcillin-clavulanic acid, and
trimethoprim-sulfamethoxazole was above 85% in both sets of isolates. Imipenem
and Fosfomycin resistance was non-existent in 2005 but ranged from 3-15% in 2009
10. Remarkable increase from 9.5% to 64.7% in urinary tract isolates and from 0
to 55% in pus isolates was observed in colistin sulphate resistance. The
dissemination of genes encoding ESBLs was: CTX-M 3.5%; TEM 10.7%; both CTX-M and
TEM 3.5% in 2005, and CTX-M 42.5%; TEM 48.1%; both CTX-M and TEM 29.6% in 2009
10. CONCLUSIONS: Our results showed very rapid emergence of multidrug resistant
ESBL producing E. coli in Pakistan posing a very serious threat in the treatment
of nosocomial and community acquired infections.
PMID- 24353574
TI - Cardioprotective Effects of Atorvastatin plus Trimetazidine in Percutaneous
Coronary Intervention.
AB - OBJECTIVE: To explore the effects of preoperative administration of conventional
doses of atorvastatin plus trimetazidine on the myocardial injury of patients
during the perioperative period of percutaneous coronary intervention (PCI).
METHODOLOGY: 475 cases of acute coronary syndrome patients before PCI were
randomly divided into the control group (238 cases) and experimental group (237
cases).The control group was treated with conventional doses of atorvastatin
calcium (20 mg each time, once a night), and the experimental group was treated
with conventional doses of atorvastatin calcium plus trimetazidine hydrochloride
(20 mg each time, tid) for 3 d. After PCI, preoperative and postoperative 24 h
concentrations of serum creatine kinase MB isoenzyme (CK-MB), cardiac troponin I
(cTnI) and high sensitivity C-reactive protein (hs-CRP) as well as activity of
myeloperoxidase (MPO) were investigated. Left ventricular ejection fractions of
the patients were then examined 4 weeks later. RESULTS: Postoperative 24 h cTnI
concentration and elevated MPO activity of the experimental group were
significantly lower than those of the control group (P <0 05). CK-MB activities
and hs-CRP concentrations of the two groups did not differ significantly (P> 0
05). CONCLUSION: The administration of conventional doses of atorvastatin plus
trimetazidine three days before PCI is able to protect the perioperative patients
from myocardial injury.
PMID- 24353575
TI - Accuracy of Non-Contrast CT Brain Interpretation by Emergency Physicians: A
cohort study.
AB - OBJECTIVE: To assess the accuracy of emergency physicians (EPs) in the
interpretation of non-contrast CT Brain (NCCT Brain) by examining the inter rater
reliability between EPs and radiology specialists. METHODOLOGY: A four months
prospective cohort study was conducted at emergency department of King Khalid
University Hospital (KKUH), Riyadh, Saudi Arabia. We studied the daily
performance of our EPs, and compared it to the radiological report issued within
the week after. Data were analyzed by calculating sensitivity, specificity,
accuracy and agreement (kappa statistic), using radiology report as the reference
standard. Results : Out of 241 cases eligible for the study, 210 (87.14%) were
concordant, and 31 (12.86%) were discordant. The agreement (kappa) was to be
0.64. Conclusion : We concluded that our EPs are moderately accurate at
interpreting NCCT Brain studies. Further education and training programs were
necessary for all our EPs to improve the accuracy. Further studies are required
to determine the most cost-effective method of minimizing consequential
misinterpretations.
PMID- 24353576
TI - The impact of chronic low back pain on physical performance, fear avoidance
beliefs, and depressive symptoms: A comparative study on Turkish elderly
population.
AB - OBJECTIVES: The purposes of this study were: (1) to show the impact of chronic
low back pain (CLBP) on physical performance, fear avoidance behavior and
depressive symptoms in older adults; (2) to describe the relationships between
outcome measurements obtained in this study. METHODOLOGY: Ninety-one participants
with or without chronic low back pain were included in this study. Only four
tests in the Back Performance Scale were used to assess the physical performance
of the participants. A Fear Avoidance Beliefs Questionnaire related to physical
activity and the Geriatric Depression Scale were also used to examine each
subject. RESULTS: The level of performance shown by elderly adults with low back
pain was worse than elders without low back pain in the sock test and the pick-up
test (p < 0.05). Little correlation between the finger-to-floor test and fear
avoidance behaviour related to physical activity was found (p < 0.05). There was
little/poor correlation between all performance tests and depressive symptoms (p
< 0.05). CONCLUSIONS: The findings indicate that CLBP decreases physical
performance, but increases fear avoidance behavior and depressive symptoms in
elderly adults. At the same time, it was determined that performance level of
elderly adults with back pain was related especially with depressive symptoms.
PMID- 24353577
TI - Chest Pain as a presenting complaint in patients with acute myocardial infarction
(AMI).
AB - OBJECTIVE: To study various characteristics of chest pain in acute myocardial
infarction patients. METHODOLOGY: A total of 331 patients of AMI admitted at
Cardiology unit Nishtar Hospital Multan and Chaudhry Pervez Elahi Institute of
Cardiology Multan, irrespective of the age and gender, were included in this
study. The study duration was one year starting from June 2011 to June 2012. Non
probability purposive sampling technique was used in this descriptive study.
Informed consent to participate in this study was taken. Data were entered and
analyzed using SPSS-11. RESULTS: A total number of 331 patients with AMI were
included in the study. Mean age was 54.99+/-11.25 years with minimum age 20 years
and maximum age 90 years. It included 264(79.8%) male and 67(20.2%) female
patients with male to female ratio of 3.9:1. Out of these 331 patients 308
(93.1%) patients reported chest pain as the presenting complaint. Remaining
23(6.9%) presented with clinical features other than chest pain. There were
127(38.4%) patients with pre-cordial chest pain, 115(34.7%) had retrosternal
chest pain, 58(17.5%) were having epigastric pain. Severe chest pain was seen in
281(84.9%) patients while 26(7.9%) had only mild chest discomfort. Radiation of
the pain to shoulder, neck and jaw was seen in 75 (22.7%) patients. In 42(12.7%)
patients, pain radiated to both sides of chest. Another 55(16.6%) patients had
pain radiation to chest, shoulder, upper arm and ulnar side of left forearm.
Chest pain radiation to interscapular region along with both sides of chest was
present in 10(3.0%) patients. In 11(3.3%) patients' pain radiated only to left
side of chest. Pain persisting for >20 minutes was reported by 298 (90%) patients
while only 10(3.1%) had pain persisting for <20 minutes. CONCLUSION: There is
considerable overlap in chest pain of cardiac as well as non cardiac causes.
However, vigilant evaluation of characteristics of chest pain in history taking
may help to overcome this dilemma. Severe and prolonged precordial chest pain in
a male patient between the age of 41-70 years, with pain radiation to left
shoulder, neck and jaw is highly suggestive of AMI.
PMID- 24353578
TI - Values of mean platelet volume in patients with chronic tonsillitis and adenoid
hypertrophy.
AB - OBJECTIVES: Chronic tonsillitis (CT)-adenoid hypertrophy (AH) is the most common
cause of obstructive sleep apnea (OSA), which is one of the most common reasons
of nocturnal hypoxia in children. However, there is limited information about the
relationship between childhood OSA and atherosclerosis or cardiac diseases. In
the present study, we evaluated the relationship between mean platelet volume
(MPV) and CT-AH which is the most frequent cause leading OSA in children.
Methodology : The medical records of 200 children, who underwent adenoidectomy or
adenotonsillectomy with a diagnosis of adenoid hypertrophy and/or chronic
tonsillitis between October, 2010 and June, 2012, and 240 healthy controls were
evaluated. Subjects were classified into 3 groups. Group I consisted of patients
who underwent adenoidectomy, whereas Group II consisted of patients who had
adenotonsillectomy. Healthy children were employed as control group. White blood
cell count (WBC), platelet count (PLT), hemoglobin (Hb) levels and mean platelet
volume (MPV) values were recorded individually. RESULTS: MPV values were 6.6+/
0.8, 6.6+/-0.7 and 7.3+/-0.9 in Group I, Group II and control group,
respectively. It was found that MPV values in groups I and II were significantly
lower than control group. There was no significant difference between group I and
II. Conclusion : Obstructive sleep apnea (OSA) caused by CT-AH is associated with
low MPV values in childhood.
PMID- 24353579
TI - The diagnosis and treatment of traumatic retroperitoneal hematoma.
AB - OBJECTIVE: To analyze our experiences in patients with traumatic retroperitoneal
hematoma, and highlight the problems in diagnosis and treatment to facilitate the
surgeons to make decision. METHODOLOGY: One hundred and eight patients of
traumatic retroperitoneal hematoma treated in our institution from May 2008 to
Jun 2012 were reviewed retrospectively. The data including patient's age, type of
injury, hospital stays, type of treatment, injured organs and mortality rate were
collected. RESULTS: In 108 patients, seventy-seven patients were male and 31 were
female with a mean age of 36.5 years; eighty-seven patients sustained blunt
trauma and 21 penetrating injury. Centro-medial hematoma was found in 31
patients, lateral hematoma in 36 patients, pelvic hematoma in 35 and pelvic
central hematoma in six patients. Eighty-three patients were treated surgically
and 25 patients were treated conservatively. Six patients died and the mortality
rate is 6.5%. Wound infection occurred in five patients, deep vein thrombosis in
one patient, gastric fistula in two patients and duodenal fistula in one patient.
CONCLUSION: Traumatic retroperitoneal hematoma is life-threatening condition,
early diagnosis and correct treatment is of upmost importance. Mandatory
exploration should be performed in cases of retroperitoneal hematomas resulting
from penetrating injury, but the selection of treatment mode in blunt injury
depends on the anatomical position of hematoma, visceral injury and the
hemodynamic status of the patients.
PMID- 24353580
TI - Reference range variation in haematological indices amongst five different age
groups of less than one year in Islamabad, Pakistan.
AB - OBJECTIVE: The objective of the current study was to establish the reference
ranges of haematological indices amongst five healthy infantile (<1 year) age
groups. METHODOLOGY: It was a descriptive cross sectional study carried out at
the Department of Haematology, Armed Forces Institute of Pathology (AFIP),
Rawalpindi. Non probability convenience sampling was adopted for the proceedings
for the study. A sample size was 2000 which was equally distributed as 400
samples for all the five age groups i.e. <27 days, 3 month, 6 month, 9 month and
one year. One thousands were males and 1000 were the females. An informed consent
from the guardian was the pre requisite of study, while those candidates having
an evidence of any systemic illness were not excluded. Results : The values of
haematological indices i.e. MCV, MCHC, MCH, PCV and RDW varies with growing age
of an infant. A decrease in all these values was observed from <27days to one
year of age infants. Conclusion : A decrease in all these values was observed
from <27days to one year of age infants. The values reported in this study can be
used as a local reference for the newborn aged between <27 days and 1 year of
age.
PMID- 24353581
TI - Extended multi-organ resection for cT4 gastric carcinoma: A retrospective
analysis.
AB - OBJECTIVE: Combined resection for locally advanced (T4) gastric cancer may result
in high morbidity and mortality. The aim of this study was to evaluate the
clinicopathologic characteristics to determine the prognostic factors for T4
gastric cancers. METHODOLOGY: A total of 463 consecutive patients with gastric
cancers were enrolled in this study. Among them, 63 patients received combined
resections. Various clinicopathologic factors influencing survival rates were
evaluated. Survival rates were calculated according to the Kaplan-Meier method.
Prognostic factors were evaluated by the univariate and multivariate analysis.
RESULTS: Thirty-one patients (49.2%) received one additional organ resection and
32 patients (50.8%) received two or more additional organ resections. Curative
resection was performed in 49 patients (77.8%). Multivariate analysis identified
curative resection (hazard ratio 0.330; 95 percent confidence interval, 0.139
0.784; P = 0.012) and tumor diameter (> 7 cm) (hazard ratio, 3.589; the 95
percent confidence interval, 1.425-9.037; P = 0.007) as independent prognostic
factor for patients with T4 gastric cancer undergoing combined resection.
CONCLUSIONS: The use of aggressive multi-organ resection was recommended for
patients with T4 gastric carcinoma, with tumor diameter as a useful indicator.
Patients with relatively small tumor diameter (<= 7cm) could benefit from multi
organ resections.
PMID- 24353582
TI - The effect of age, sex and obesity on fundamental motor skills among 4 to 6 years
old children.
AB - OBJECTIVE: To examine the effect of age, sex and obesity on Fundamental Motor
Skills (FMS) in 4 to 6 years-old children. METHODOLOGY: A total of 400 preschool
children (200 boys and 200 girls) between the ages of 4 to 6 years old
participated in this research. Subjects were selected through multi-stage cluster
random sampling. Fundamental motor skills (FMS) were assessed with using the OSU
SIGMA scale. Body mass index (BMI) was directly measured from
height(m)(2)/weight(kg) for each child and based on CDC growth charts, normal
weight, overweight and obesity were defined. RESULTS: The results showed that age
and sex variables were a significant effect on walking and running skills, but
BMI was not significant (P>0.05). Also, these variables had a significant effect
on jumping, skipping, hopping and ladder climbing. In both ages, boys in jumping
and ladder climbing skills were better than girls, but the girls were better in
skipping and hopping skills (P<0.05). Moreover, the results showed that age and
BMI variables have a significant effect on stair climbing skill, but sex was not
significant (P>0.05). For object control skills, the results showed that age and
sex variables were a significant effect on catching and throwing skills, but BMI
was not significant (P>0.05). Finally, the age, sex and BMI variables were a
significant effect on kicking and sticking skills. CONCLUSION: This research
demonstrated that boys performed better than girls, and both overweight and obese
children have lower performance than normal children.
PMID- 24353583
TI - Intravitreal Avastin as an adjunct in patients with proliferative diabetic
retinopathy undergoing pars plana vitrectomy.
AB - OBJECTIVE: Intravitreal Bevacizumab (Avastin, Genentech Inc., San Francisco, CA)
(IVB) has been shown to cause regression of neovessels in proliferative diabetic
retinopathy due to its anti-angiogenic effects. This study was performed to
investigate the role of Avastin as an adjunct to the management of patients with
proliferative diabetic retinopathy undergoing pars plana vitrectomy. METHODOLOGY:
Fifty four eyes of 54 patients with proliferative diabetic retinopathy scheduled
for surgery were included in the study. They were randomized to vitrectomy with
preoperative IVB (group one) or standard vitrectomy (group 2). Group one
underwent a single intravitreal injection of bevacizumab 1.25 mg /0.05ml one week
prior to vitrectomy. Main outcome measures were best corrected visual acuity
(BCVA) after surgery, post-operative complications. RESULTS: Mean age of the
patients was 52.07+/-5.54 years (range 39-67). At 6 months, 20 patients in group
one had BCVA better than baseline as compared to 12 patients in group 2. In group
one, only one patient had early post-operative vitreous hemorrhage, whereas 11
patients in group two had early vitreous hemorrhage. CONCLUSION: Preoperative IVB
is helpful in improving BCVA post operatively, reducing the time of surgery,
decreasing the incidence of intraoperative and postoperative bleeding and
reducing the frequency of rubeosis and hyphaema.
PMID- 24353584
TI - Prevalence and clinical profile of insulin resistance in young women of poly
cystic ovary syndrome: A study from Pakistan.
AB - OBJECTIVE: The aim was to estimate the prevalence of Insulin Resistance (IR) in
Poly Cystic Ovary Syndrome (PCOS) and analyze its clinical parameters.
METHODOLOGY: This observational study was conducted at Dow University Hospital
during June 2011 till May 2012. Patients of PCOS were selected, an anthropometric
measurement, examination and fasting blood test for sugar (FBS) and insulin was
performed. Data was collected on pre designed questionnaire, was analyzed by SPSS
version 16. RESULTS: Forty-six cases of PCOS were included in the study.
Prevalence of IR was 34.78%. Mean age of patients was 23.72 +/- 4.37 years. Waist
Hip Ratio (WHR) was raised in 42 (91.30%), acanthosis was found in 26(56.50%),
impaired FBS was seen in 9 (19.6%) and raised fasting insulin in 16 (34.8%)
patients. There was significant association between acanthosis and WHR (0.044)
and between acanthosis and FBS (0.008). Correlation studies between parameters
showed a significant correlation between Waist & Hips (0.93), similarly Waist &
WHR showed positive correlation (0.59), at p< 0.01. Significant positive
correlation was also found between waist and FBS (0.32) and FBS & WHR (0.378).
CONCLUSION: Acanthosis nigrican, raised WHR and FBS are significant parameters
for insulin resistance in cases of Poly Cystic Ovary Syndrome (PCOS).
PMID- 24353585
TI - Psychosocial Rehabilitation Training in the Treatment of Schizophrenia
Outpatients: A Randomized, Psychosocial Rehabilitation training-and
Monomedication-Controlled Study.
AB - OBJECTIVE: This study was designed to evaluate the efficacy of psychosocial
rehabilitation intervention on schizophrenia. METHODOLOGY: One hundred forty
schizophrenia outpatients in remission stage were randomized to either an
antipsychotic monomedication (control group) or an antipsychotic monomedication
plus a psychosocial rehabitation training (trial group). Positive and Negative
syndrome Scale (PANSS), Disability Screening Schedule (SDSS) were performed
longitudinally from baseline to month 18 to evaluate the efficacy. RESULTS:
Significant difference in relapse rate between the control group (42.9%) and the
trial group (18.6%) was found at month 18. In patients who didn't relapse, the
trial group showed significantly lower PANSS and SDSS score (P<0.05) than did the
control group after treatment. CONCLUSION: Psychosocial rehabilitation
intervention could produce a better outcome in terms of reducing relapse and
improving the social functioning in schizophrenia.
PMID- 24353586
TI - Comparison of postoperative complication between Laryngeal Mask Airway and
endotracheal tube during low-flow anesthesia with controlled ventilation.
AB - OBJECTIVE: To compare the postoperative complications between Laryngeal Mask
Airway (LMA) and endotracheal tube (ETT) during low-flow anesthesia with
controlled ventilation. METHODOLOGY: Eighty adult Patients with ASA class I or II
were randomly allocated into two forty-patient groups (ETT or LMA). Cuff pressure
was monitored during anesthesia. After high uptake period, fresh gas flow (FGF)
was decreased to 1 lit/min and isoflurane set to 1%. Monitoring during anesthesia
included non-invasive blood pressure, ECG, ETCO2 and pulse oximetry. System
leakage (>100 ml/min), rebreathing and any attempt to increase FGF to overcome
the leak were monitored during anesthesia. Later, patients were extubated and
transferred to Post Anesthesia Care Unit (PACU). In PACU, the incidence of sore
throat, cough, difficulty in swallowing and shivering was monitored for all
patients. RESULTS: Leakage was observed in two and three cases in ETT and LMA
groups respectively (P>0.05). Postoperative cough, sore throat and difficulty in
swallowing were significantly less in LMA than ETT group. No significant
difference was observed regarding ETCo2 values between 2 groups. CONCLUSION: If
careful measures regarding insertion techniques, correct LMA position and routine
monitoring of LMA cuff pressure are taken, LMA can be used as a safe alternative
with lower incidence of post operation complication compared with ETT during low
flow controlled anesthesia with modern anesthetic machines.
PMID- 24353587
TI - Gender determines the effect of atracurium priming technique in a randomized
study.
AB - OBJECTIVE: To evaluate the effect of priming atracurium over onset time and
intubating time of general anesthesia between different genders. METHODOLOGY:
Sixty-six male and sixty-four female patients, ASA I-II, aged 18-65 years, were
randomly divided into four groups: group M1: male patients with saline priming;
group M2: male patients with priming atracurium dose of 0.05 mg/kg; group F1:
female patients with saline priming; group F2: female patients with priming
atracurium dose of 0.05 mg/kg. General anesthesia was induced with midazolam(0.1
mg*kg(-1)) propofol(0.75 mg*kg(-1)), intubation dose of atracurium (0.5 mg*kg(
1)), fentanyl (3 MUg*kg(-1)). The incidences of dizziness, diplopia, heavy
eyelids and dyspnea were observed. Neuromuscular tension was quantified by using
TOF-Guard neuromuscular monitor, and intubating time was defined as the duration
from the infusion of intubation dose of atracurium to the time when T4/T1=0.
RESULTS: The intubating time of group F2 was shorter than that of group F1. There
was no significant difference between group M1 and group M2. The incidences of
dizziness, diplopia and heavy eyelids in group F2 were higher than those in group
M2. CONCLUSION: Atracurium priming technique could shorten the intubation time of
female patients, but not for male patients, and the gender plays a key role in
affecting the clinical outcome of atracurium priming.
PMID- 24353588
TI - The expressions of AMACR and iNOS in prostate adenocarcinomas.
AB - BACKGROUND AND OBJECTIVE: Prostate cancer is the second leading cause of death in
men. The localized disease often responds to conventional therapies like androgen
ablation via castration and/or administration of chemical inhibitors but advanced
disease resistant to any curative therapies is still challenge for investigators.
There are increasing efforts to enhance the possibility of finding positive and
sensitive immune markers for diagnosing and treating prostate cancer. The aim of
this study was to investigate the expression patterns of AMACR and iNOS in
prostate adenocarcinomas with different histopathologic grade. METHODOLOGY: We
applied immunohistochemical markers; AMACR and iNOS. Formalin-fixed parafin
embedded tissues of 64 prostate needle biopsy specimens diagnosed as prostate
adenocarcinoma between 2005-2010 years were included in the study. RESULTS: AMACR
expression were found in 58 (90.6%) and iNOS expression in 54 (84.4%) of 64
prostate adenocarcinomas. No significant relationship of AMACR and iNOS was
obtained (p>0.05). There was no significant correlation of histopathologic grade
of the tumors with AMACR and iNOS expression (p>0.05). CONCLUSIONS: The
expression of AMACR and iNOS might be important diagnostic immune markers for
prostate adenocarcinomas especially in needle biopsies where the quantity and
quality of tissue are limited.
PMID- 24353589
TI - Nutritional status in mentally disabled children and adolescents: A study from
Western Turkey.
AB - OBJECTIVE: To assess the nutritional status of mentally disabled children in
Turkey on the basis of anthropometric indicators and dietary intake. METHODOLOGY:
The sample of the study consisted of 77 mentally disabled children with ages
between 10 and 18 years. The body mass index and body fat ratios of the children
were calculated by measuring their body weight, height, and the skinfold
thickness of their triceps and subscapular. Their three-day nutrition consumption
was recorded in order to determine their nutrient intake. RESULTS: When the body
weights of the children were evaluated according to their ages, 14.3% of the
children were found to be thin. The shortness rate among the participants was
28.6%. The shortness ratio was found to increase with age and girls had a higher
inclination for shortness than boys. The ratios of those with <=5(th) percentile
upper middle arm circumference were 32.7% in the 10-13 age group, and 36.0% in
the 14-18 age group. The folic acid and calcium intakes of girls in the 10-13 age
group, and the calcium intakes of boys in the 10-13 age group were under the
suggested values. In the 14-18 age group the vit C and calcium intakes of girls
and the calcium intakes of boys were under the recommended values. CONCLUSIONS:
The prevalence of malnutrition is high among mentally disabled children. In order
to raise their quality of life, mentally disabled children must be provided with
sufficient nutritional support.
PMID- 24353590
TI - Investigation of the effects of graded models on the biomechanical behavior of a
bone-dental implant system under osteoporotic conditions.
AB - OBJECTIVE: To investigate the effects of graded models on the biomechanical
behavior of a bone-implant system under osteoporotic conditions. Methodology : A
finite element model (FEM) of the jawbone segments with a titanium implant is
used. Two types of models (a graded model and a non-graded model) are
established. The graded model is established based on the graded variation of the
elastic modulus of the cortical bone and the non-graded model is defined by
homogeneous cortical bone. The vertical and oblique loads are adopted. The max
von Mises stresses and the max displacements of the cortical bone are evaluated.
RESULTS: Comparing the two types of models, the difference in the maximum von
Mises stresses of the cortical bone is more than 20%. The values of the maximum
displacements in the graded models are considerably less than in the non-graded
models. CONCLUSIONS: These results indicate the significance of taking into
account the actual graded properties of the cortical bone so that the
biomechanical behavior of the bone-implant system can be analyzed accurately.
PMID- 24353591
TI - The Effects of Intraarticular Opioids in pain relief after Arthroscopic
Menisectomy: A Randomized Clinical Trial Study.
AB - OBJECTIVE: Knee arthroscopy is a painful procedure which if untreated will cause
intensive and prolonged pain that may prevent rehabilitation of patients. This
study was designed to compare the analgesic effects of different opioids in the
early post operative period in comparison to control group. METHODOLOGY: One
hundred forty patients were prospectively assigned to four groups randomly. After
arthroscopic menisectomy all patients received an intraarticular injection
containing 9.5 ml bupivacaine 0.5% with 1:200000 epinephrine in a 10 ml syringe.
The remainder of syringe was filled with one of the study solutions. Group I: 5mg
methadone, group II: 5mg morphine, group III: 5 ml normal saline, group IV: 50 mg
meperidine. At three stages in the ealy post operative period the need for
analgesics was recorded. A statistical comparison was done afterwards. Results :
In morphine group (group II), the analgesic usage in hospitalized and outpatients
compared with other groups was significantly low(P<0.05). CONCLUSION: Morphine in
comparison to meperidine or methadone is more beneficial in reducing pain or
analgesic need when is added to bupivacain injection following arthroscopic
menisectomy.
PMID- 24353592
TI - Seroprevalence of hepatitis e virus among primary school children.
AB - OBJECTIVES: To investigate the seroprevalence of anti-hepatitis E virus antibody
among primary school children in the two different areas of Denizli, Turkey.
Methodology : Anti-HEV antibodies were investigated in 185 primary school
children (91 from rural areas and 94 from urban areas of Denizli). The children
were divided into two age groups as seven-year old group and fourteen-year old
group. Samples were tested for anti-HEV Ab by an enzyme-linked immunoassay.
Results : A total of 23 primary school children were anti-HEV Ab positive, giving
a prevalence of 12.4%. The seroprevalence rate was 13.1% in rural areas and 11.7%
in urban areas. The difference in the seropositive rates was not statistically
significant (p>0.05). Among 185 primary school children, Anti-HEV antibodies were
positive 17 (18.1%) in seven-year old group, and 6 (6.6%) in fourteen-year old
group. The difference in the seropositive rates was statistically significant
(p<0.05). Conclusions : There was no association between the anti-HEV Ab and
gender, socioeconomic level, parental educational level, rural or urban areas.
Anti-HEV Ab seroprevalence was higher in seven-year old children than fourteen
year old children.
PMID- 24353593
TI - Clinical outcome of endoprosthetic replacement for failed treatment of
intertrochanteric fractures: A retrospective case series.
AB - OBJECTIVE: The treatment methods for the failed internal fixation in elderly
patients suffering from several osteoporostic fractures are still inconclusive.
We aimed to evaluate the clinical effects of endoprosthetic replacement for
failure treatment of intertrochanteric fracture. METHODOLOGY: A total of 13
patients with failed internal fixation for intertrochanteric fracture were
collected between January 2002 and October 2009. All of them were treated with
endoprosthetic replacement and followed up till October 2010. Four of them
received total hip replacement and the remained nine received artificial bipolar
femoral head replacement. Clinical and functional outcomes of patients were
assessed. RESULTS: Of 13 patients, nine were females and four were males with the
mean age of 76.5 years (SD, 11.7, range, 58-92 years) at the time of fracture.
The average time of operation and follow-up was 124 minutes (89-187minutes) and
31 months (14-68 months), respectively. The average blood loss during the
operation was 631 ml (450-1560 ml). All patients showed good pain relief and
functional improvement. Final post-operative Harris and WOMAC scores were
significantly improved from pre-operative levels (P<0.05). Only five patients
showed operative complications. CONCLUSIONS: Our finding indicated that
endoprosthetic replacement is an effective salvage procedure for failed internal
fixation of intertrochanteric fracture in elderly patients with effective pain
relief and functional improvement as well as few serious complications.
PMID- 24353594
TI - Evaluation of thyroid dysfunction in pregnant women with gestational and pre
gestational diabetes.
AB - OBJECTIVE: The aim of this study was to investigate thyroid function tests in
Gestational Diabetes Mellitus (GDM) and pre-gestational DM and control group.
Methodology : There were 61 pregnant diabetic women in study group and 35
pregnant women in control group. Serum T4, T3, T3RU, FTI, TSH and Anti TPO Ab
were assessed in each person. Results : About 36% of patients had GDM and 64% pre
gestational DM. Thyroid dysfunction was detected in 18% of study group compared
with 8.6% of control group (P = 0.2). There was Thyroid dysfunction in 4.5% of
GDM and 25.6% of pregestational DM (P = 0.045). There was no statistically
significant difference between thyroid dysfunction in GDM group and control group
(P=0.99).27% of GDM and 36% of pregestational DM and 23% of control group had
positive titer of Anti TPO Ab without statistically significant differences among
the three groups. Conclusion : Thyroid dysfunction is prevalent in women with pre
gestational DM so, thyroid function should be evaluated in these patients during
pregnancy. Rate of thyroid dysfunction in GDM patients is similar to normal
pregnant control women. High prevalence of positive titer of TPO Ab was seen in
diabetic and non-diabetic pregnant women.
PMID- 24353595
TI - Respiratory and general health complaints in subjects exposed to sandstorm at
Riyadh, Saudi Arabia.
AB - OBJECTIVE: Sandstorms are metrological events and frequently occur in many
regions throughout the world. Sandstorms are a main source of long-distance
transport of dust, air pollution and cause various health problems. This study
aimed to investigate the acute respiratory and general health complaints in
subjects exposed to sandstorm at Riyadh, Saudi Arabia. METHODOLOGY: The present
descriptive study was conducted in the Department of Physiology, College of
Medicine, King Saud University, Riyadh, Saudi Arabia during the period March 2011
June 2012. We selected 517 (308 males, 59.58%) and (209 females, 40.42%),
apparently healthy volunteers with mean age 28.6+/- 3.14 years, who had single
outside exposure to sandstorm for the period of 24+/-2.68 minutes. The acute
respiratory and general health complaints were recorded through a comprehensive
questionnaire. RESULTS: A large proportion of the subjects who were exposed to
sandstorm had complaints of cough 247 (47.77%), runny nose 264(51.06%), wheeze
173(33.46%), acute asthmatic attack 108 (20.88%), eye irritation / redness
252(48.74%), headache 179 (34.62%), body ache 199 (38.5%), sleep disturbance
157(30.36%) and psychological disturbances 194 (37.52%). CONCLUSION: Exposure to
sandstorm causes cough, runny nose, wheeze, acute asthmatic attack, eye
irritation / redness, headache, body ache, sleep and psychological disturbances.
These results indicate that sandstorm is a prolific source of respiratory and
general ailments. It is therefore, suggested that an unnecessary exposure to
sandstorm must be avoided.
PMID- 24353596
TI - Efficacy of Paraffin Wax Bath with and without Joint Mobilization Techniques in
Rehabilitation of post-Traumatic stiff hand.
AB - OBJECTIVE: Post-traumatic stiff hand is common a condition which causes pain and
disability, the paraffin wax bath and joint mobilizations have the key role in
its rehabilitation. We conducted the present study to determine the efficacy of
paraffin wax bath with mobilization techniques compared with joint mobilization
alone. METHODOLOGY: This single blind randomized control trial was conducted on
71 patients in department of physical therapy and rehabilitation, Riphah
International University Islamabad, and patients with post-traumatic stiff hand
after distal upper extremity fractures, were included. The patients were
randomized into two groups: the joint mobilization techniques with paraffin wax
bath were included in group A, and joint mobilization techniques without paraffin
wax bath in group B. The study variables were pain score on visual analogue scale
(VAS) 0/10, thumb function score (TFS) and passive range of motion (PROM) of
wrist flexion, extension, radial and ulnar deviation, and were compared at
baseline and at completion on plan-of-care after six weeks. RESULTS: Seventy one
patients with post-traumatic stiff hand were enrolled and placed randomly into
two groups. The baseline characteristics were similar in both groups. Six week
after intervention, patients in group A had more improvement in pain score
(p=0.001), TFS (p=0.003), and PROM of wrist flexion (p=0.002), extension
(p=0.003), radial deviation (p=0.013), and ulnar deviation (p=.004), as compared
to group B. However, in group B the improvement was less in pain score (p=0.104),
TFS (p=0.520), and PROM of wrist flexion (p=0.193), extension (p=0.1081), radial
deviation (p=0.051), and ulnar deviation (p=.168), as compared to group A.
CONCLUSION: Paraffin wax bath with joint mobilization techniques are more
effective than mobilization techniques without paraffin wax bath in the
rehabilitation of post traumatic stiff hand.
PMID- 24353597
TI - Fertility sparing treatment in young patients with early endometrial
adenocarcinoma: case series.
AB - OBJECTIVE: The aim of this study was to evaluate fertility-sparing therapy in
young patients with endometrial carcinoma. METHODOLOGY: This prospective study
was carried out on 8 patients with clinical and radio-graphic stage IA, well
differentiated endometrioid adenocarcinoma of the endometrium in Alzahra
hospital, Tabriz, Iran. Treatment comprised high-dose megestrol acetate.
Dilatation and curettage was repeated every three months. RESULTS: The mean age
of the patients was 30 (SD,3.21) years (range 24-35). Of the 8 patients, 7
(87.5%) achieved complete response. The mean time to response was 6.5 months
(range 3-9). Of the complete responders, 3 of 7(42.8%) had recurrence; one
patient underwent immediate hysterectomy, and 2 were successfully treated with
second-line therapy and both subsequently conceived. Conception occurred in 3 of
7 patients (42.8%), in two more than once, However successful pregnancy occurred
only in two patients. One patient developed Concomitant ovarian adenocarcinoma.
CONCLUSIONS: High dose progestin therapy can be an effective fertility-sparing
treatment in young patients with well differentiated stage IA endometrial
endometrioid cancer confined to endometrium. However, close follow up is required
because of risks of conservative treatment.
PMID- 24353598
TI - Intragastric rupture of splenic artery aneurysms: Three case reports and
literature review.
AB - Rupture of splenic artery aneurysm remains an uncommon cause of hypovolemic shock
although it is the third most common intra-abdominal aneurysms. It is difficult
to diagnosis timely and entails a significant morbidity and mortality. We present
three uncommon cases of bleeding from upper gastrointestinal tract as a result of
rupture of splenic artery aneurysm to stomach in patients with liver cirrhosis or
infectious endocarditis. We also reviewed the literature and these case reports
highlighted that rapid resuscitation, diagnostic imaging, surgical consultation,
and alternatively transarterial embolization were the priorities in the
management. Early diagnosis and intervention for ruptured splenic artery aneurysm
are crucial for patient's survival; therefore, it must be kept in mind as
feasible etiology of life-threatening gastrointestinal bleeding, especially in
patients with underlying liver cirrhosis or infective endocarditis.
PMID- 24353599
TI - Lamellar ichthyosis with rickets.
AB - Lamellar ichthyosis (LI) is a rare genetic disorder with autosomal recessive
inheritance. It is equally seen in both sexes and usually manifests at birth. The
child presents as a collodion baby. The erythema is minimal or absent; but when
present, it is maximum on the face. The scaling is generalized, accentuated on
lower extremities and flexural areas. Rickets is a condition in which there is
softening of bones leading to fractures and deformities. It is caused by vitamin
D deficiency & lack of adequate calcium in diet. Children, 6 to 24 months of age,
are at a higher risk due to rapidly growing bones. The association between
various types of ichthyoses and rickets is well documented. We report a case of
lamellar ichthyosis with rickets in a 14-year-old girl from our part of the
world.
PMID- 24353600
TI - Treatment of gestational choriocarcinoma and massive ascites by hypothermic
intraperitoneal perfusion chemotherapy guided by ultrasound followed by
cytoreductive surgery.
AB - A 33-year-old woman with very poor health status was admitted to our hospital
because she had experienced increasing abdominal distention for three months, CT
examination showed a right ovarian tumor together with massive abdominal and
pelvic fluid. The patient was first treated by continuous circulatory hypothermic
intraperitoneal perfusion chemotherapy (HIPC) guided by B-mode ultrasound,
followed by cytoreductive surgery (CRS) after her ascites was controlled and her
health condition improved. She was diagnosed with gestational choriocarcinoma
(GC) based on the pathological examination of the hysterectomy specimen. She is
still alive with very good health today. We think it may be a good choice for a
patient in very poor health with GC accompanied by massive ascites to perform
HIPC guided by B-mode ultrasound firstly, followed by CRS when the ascites has
relieved and the patient's health has improved.
PMID- 24353601
TI - A case of mycotic aneurysm due to Burkholderia pseudomallei.
AB - Burkholderia pseudomallei is an free-living gram-negative bacterium causing
melioidosis and is endemic in Southeast Asia. A 56-year-old diabetic construction
worker with a 1-month history of abdominal pain and 1-day history of high-grade
fever was found to have a left non-dissecting infrarenal mycotic aortic aneurysm
by abdominal computerized tomography scan. Bacteriological examination of his
blood yielded Burkholderia pseudomallei. The patient was treated with right
axillo-bifemoral bypass with excision of aneurysm and high-dose intravenous
ceftazidime for two weeks, followed by oral trimethoprim/sulfamethoxazole and
oral doxycycline for a minimum of five months.
PMID- 24353602
TI - "One-stop" Hybrid approach for tetralogy of fallot with aortopulmonary collateral
arteries in adults.
AB - We report a 45 year-old Chinese woman with tetralogy of fallot that had two
aortopulmonary collateral arteries and tricuspid regurgitation. Collateral
circulation was blocked and total correction was successfully performed in our
"one-stop" hybrid operation room. The patient was weaned from cardiopulmonary
bypass after 97 minutes and was transferred to the intensive care unit for about
36 hours. Without any complications, the patient was discharged home in the
following eight days.
PMID- 24353603
TI - Neuropathic pain in hereditary coproporphyria.
AB - Acute porphyrias are rare diseases with varying incidences worldwide. These
diseases are disorders of heme biosynthesis characterized by acute attacks of
neurological symptoms. Acute porphyria should be considered in patients with
unexplained abdominal pain or neurological damage. Clinical manifestations of
acute porphyria are nonspecific and are associated with multiple organ systems.
This report examines a rare case of an uncommon type of acute porphyria in a
patient with an initial presentation of abdominal pain and progressive
polyneuropathy.
PMID- 24353604
TI - Case scenario about TEE: Patient with dilated cardiomyopathy undergoing
laparoscopic cholecystectomy.
AB - A 42-year-old woman, who presented with DCM (American Society of Anesthesia, ASA
class IV), suffered from gallstone for years, and was scheduled for laparoscopic
cholecystectomy. Echocardiography demonstrated a severely dilated left ventricle
with global hypokinesia and reduction of left ventricular systolic function,
ejection fraction (EF) 34% with mild mitral regurgitation and severe tricuspid
regurgitation. After intubation, a transesophageal echocardiography (TEE) probe
was inserted. When the IAP was gradually ascended to 14 mmHg during the
laparoscopy, EF fell to 19% and the systolic pressure fell to 78 mmHg and TEE
showed severely poor wall motion. But the central venous pressure (CVP) still
showed about 4 mmHg throughout the whole procedure. After decreasing the IAP to
10 mmHg, we adjusted the rate of pacemaker to 70 times per minute then the
systolic pressure was kept at around 100 mmHg, and the diastolic pressure was
kept at 60 mmHg. EF was 30% after the reduction of IAP and the adjusting of the
heart rate set. TEE is a helpful monitor in anesthesia management of patients
with DCM during noncardiac surgery and CVP is useless especially for the
procedure with severe hemodynamic effects.
PMID- 24353605
TI - Prevalence of Overweight and Obesity among Female Adolescents in Jordan: A
comparison between Two International Reference Standards.
AB - OBJECTIVE: To find out the prevalence of overweight and obesity among female
adolescents in Jordan. METHODOLOGY: A cross-sectional survey on females aged 15
18 in Amman, Jordan, was carried out using a multistage stratified random
sampling method. The total sample size was 475 girls. Weight and height were
measured and body mass index for age was used to determine overweight and obesity
using the IOTF and WHO international standards. RESULTS: The prevalence of
overweight and obesity decreased with age. The highest prevalence of overweight
and obesity was reported at age 15 (24.4% and 8.9%, respectively). The WHO
standard showed a higher prevalence of obesity than the IOTF standard in all age
groups. CONCLUSIONS: Overweight and obesity are serious public health problems
among adolescents in Jordan, using both international standards. A program to
combat obesity among schoolchildren, therefore, should be given a high priority
in school health policy in Jordan.
PMID- 24353606
TI - Medical literature review: Search or perish.
AB - Literature review is a cascading process of searching, reading, analyzing, and
summing up of the materials about a specific topic. However, searching the
literature is like searching "a needle in a haystack", and hence has been called
"Cinderella".(1) Therefore, skills and effective pathways of searching the
literature are needed to achieve high sensitive and specific results.
PMID- 24353607
TI - Detection of Vancomycin Resistant Enterococci from Rectal Swab Samples by Becton
Dickinson GeneOhm VanR assay and Culture at ICU of a Tertiary Care Center in
Turkey.
AB - OBJECTIVES: Vancomycin resistance is due to change in ligase enzyme that destroys
the binding of the drug. The gold standard is culture; but now molecular methods
have also been developed. The aim was to detect the VRE rate at ICUs by culture
and BD GeneOhmTM VanR and compare the results of both assays. METHODOLOGY: 135
perianal swabs were taken from the patients at ICUs between January 1(st) 2009
and April 30(th) 2009. Samples were identified by conventional methods and BD
GeneOhm VanR assay. RESULTS: In newborn ICU, 41 patients (74.6%) were negative by
both methods. Two (3.6%) were positive by both methods. Twelve (21.8%) of them
were culture negative and PCR positive. In adult ICU, 73 (91.3%) patients were
negative by both methods. Seven patients (8.8%) were positive by molecular method
only. CONCLUSION: This study showed low VRE positivity due to factors like
inhibition in PCR or culture negativity due low inoculum for bacterial growth.
Early detection of VRE is an important issue especially in ICUs and molecular
techniques are important tools; but against all, we still need to confirm this
method with culture based techniques and in order to do this further studies with
higher number of patients with VRE colonisation are required.
PMID- 24353608
TI - The injuries to the fourth and fifth tarsometatarsal joints: A review of the
surgical management by internal fixation, arthrodesis and arthroplasty.
AB - The surgical management to the injuries of the fourth and fifth tarsometatarsal
(TMT) joints is controversial. We briefly review the anatomical characteristics
to the injuries, the diagnosis, as well as the individualized treatment of the
injuries of the fourth and fifth TMT joints by open reduction and internal
fixation, TMT arthrodesis and arthroplasty. We conclude that open reduction and
internal fixation is the recommended option for acute injuries, while arthrodesis
can be used in cases of malunion of the fourth and fifth TMT joints with gross
pain or arthritic changes and obvious structural deformity. Arthroplasty is an
effective salvage operation mainly used in high-demand patients with severe TMT
arthritis. Finally, we propose a recommended treatment algorithm (based on the
literature and our experience), taking into account the specific indications for
internal fixation, TMT arthrodesis and arthroplasty to optimize the
individualized treatment. Data sources/Study selection Data from survey reports,
descriptive, cross-sectional and longitudinal studies published from 2002 to 2012
on the topic of the injuries to the fourth and fifth tarsometatarsal joint on
human and radiography studies were included. Data Extraction The data was
extracted from online resources of American Orthopaedic Foot & Ankle Society,
American Academy of Orthopaedic Surgeons, US National Library of Medicine, The
MEDLINE. Conclusion It is important to comprehend the specific anatomical
characteristics and grasp the strict indications, advantages and disadvantages of
the ORIF, TMT arthrodesis and arthroplasty to optimize the individualized
treatment of the fourth and fifth TMT joints injuries in a maximum extent.
PMID- 24353609
TI - Methylenetetrahydrofolate reductase genetic polymorphisms and esophageal squamous
cell carcinoma susceptibility: A meta-analysis of case-control studies.
AB - OBJECTIVES: Genetic factors and environmental factors play a role in pathogenesis
of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the
association of folate intake and Methylenetetrahydrofolate reductase C677T
polymorphism with ESCC was conflicting. We conducted a meta-analysis to
investigate the association of MTHFR C677T and folate intake with esophageal
cancer risk. METHODOLOGY: MEDLINE, EMBASE and the Chinese Biomedical Database
were searched in our study. The quality of studies were evaluated by predefined
scale, and The association of polymorphisms of MTHFR C677T and folate intake and
ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs).
RESULTS: Nineteen studies (4239 cases and 5575 controls) were included for meta
analysis. A significant association was seen between individuals with MTHFR 677
CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC
risk (p<0.05). Low intake of folate had significantly higher risk of esophageal
cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high
intake of folate did not find significant high risk of esophageal cancer among
individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. CONCLUSIONS: Our meta
analysis indicated the folate intake and MTHFR 677CT/TT are associated with the
risk of ESCC, and folate showed a significant interaction with polymorphism of
MTHFR C677T.
PMID- 24353610
TI - The terminator "Non-sense mediate mRNA decay": Its role in the termination of
intron containing a premature termination codon.
PMID- 24353611
TI - Academic misconduct among students in medical colleges of Karachi, Pakistan.
AB - OBJECTIVE: To determine the trends of academic misconduct in undergraduate
students of different private and government section medical institutes.
METHODOLOGY: This cross sectional study was conducted at three medical colleges
of Karachi, Pakistan. The students were evaluated by giving a self reported
questionnaire containing various questions assessing their educational dishonesty
and cheating behaviors. RESULTS: A total of 274 students from different years
completed the questionnaire. Mean age was 21.48 +/- 1.89 years. Most of the
students were in 4(th) year (n=86; 31.3%). There were 182 (66.5%) females and 92
(33.5%) males. Majority of the students (n=155; 55.1%) accepted that they have
cheated at least once. There was no significant difference regarding acceptance
of cheating among different years of study (p=0.23) however females were found to
accept cheating more as compared to males (p=0.036). First year students were
found more to ask teachers for answers during OSCE (p=0.01). A large number of
students accepted that they mark proxy for their friends (85.7%) and also ask
their friends to mark proxy for them (85.03%). Nearly half (44.02%) of the
students rotating in wards also admitted to write fake histories. CONCLUSION: A
large number of medical students admitted cheating and involvement in other
academic misconduct. We need to improve our educational system, formally add
professional session and strict disciplinary action should be taken against those
who are found guilty.
PMID- 24353612
TI - Evidence-based Health Care Continuing Education Seminars Improve Academic Staff
Knowledge and Attitudes in Saudi Arabia.
AB - OBJECTIVE: To assess the influence of a monthly evidence-based health care (EBHC)
seminar series on academic staff knowledge, attitudes, and barriers regarding
EBHC practice. METHODOLOGY: All academic staff in the College of Applied Medical
Sciences (CAMS), King Saud University, Saudi Arabia, were sent a validated web
based survey. The survey contained 35 items regarding 3 domains: knowledge (14
items), attitudes (11 items), and barrier factors (10 items). A 5-point Likert
scale was used and descriptive statistics were generated for demographic data and
participants' responses to each item. RESULTS: Among academic staff at CAMS, 79
of 198 (40%) completed the survey. Among the survey respondents, 58% had attended
at least one EBHC seminar. Those who had attended at least one seminar had better
knowledge of 8 items compared with those who did not attend any seminars (P<.05).
Academic staff members who attended at least one seminar were more likely to have
a positive attitude regarding EBHC. Insufficient time was the only factor that
significantly differed between the 2 groups, serving as a barrier to EBHC
practice. CONCLUSIONS: Our findings suggest that EBHC seminars may improve the
abilities and skills of academic staff for using EBHC.
PMID- 24353614
TI - Identification of technical item flaws leads to improvement of the quality of
single best Multiple Choice Questions.
AB - OBJECTIVE: The purpose of the study was to identify technical item flaws in the
multiple choice questions submitted for the final exams for the years 2009, 2010
and 2011. METHODS: This descriptive analytical study was carried out in Islamic
International Medical College (IIMC). The Data was collected from the MCQ's
submitted by the faculty for the final exams for the year 2009, 2010 and 2011.
The data was compiled and evaluated by a three member assessment committee. The
data was analyzed for frequency and percentages the categorical data was analyzed
by chi-square test. RESULTS: Overall percentage of flawed item was 67% for the
year 2009 of which 21% were for testwiseness and 40% were for irrelevant
difficulty. In year 2010 the total item flaws were 36% and 11% testwiseness and
22% were for irrelevant difficulty. The year 2011 data showed decreased overall
flaws of 21%. The flaws of testwisness were 7%, irrelevant difficulty were 11%.
CONCLUSION: Technical item flaws are frequently encountered during MCQ
construction, and the identification of flaws leads to improved quality of the
single best MCQ's.
PMID- 24353613
TI - Educating tomorrow's doctors: A cross sectional survey of emotional intelligence
and empathy in medical students of Lahore.
AB - OBJECTIVE: Medical education in Pakistan traditionally emphasizes physician's
biomedical knowledge with less emphasis on interpersonal skills and ability to
relate to the patients. This study explored the emotional intelligence & empathy
of undergraduate medical students and investigated its relationship with various
factors to act as baseline for future work in this area. METHODOLOGY: The Schutte
Emotional Intelligence scale and Davis' Interpersonal Reactivity Index in
addition to socio demographic questionnaire were administered to first year and
final year medical undergraduates of two medical Institutions in Lahore,
Pakistan. Data was analyzed by using SPSS 17 version. RESULTS: The overall mean
scores for medical students both on emotional intelligence and empathy is
significantly lower than that found in previous literature, highlighting that
medical students do not appear to fare better than average people in EQ. Women
showed statistically significant higher scores on Appraisal of emotions ,
Regulation of emotions, Empathic concern Scale & Personal distress scale.
Comparison of EI & IRI of students according to medical college year did not show
any statistical significance. CONCLUSION: Current medical curriculum and training
in Pakistan does not appear to increase EI abilities which are building blocks
that may allow students and residents to develop competence. Medical educators in
Pakistan should look for ways to incorporate emotional intelligence in medical
curriculum which will ultimately contribute towards patient centered practice,
patient satisfaction as well as effective communication skills.
PMID- 24353615
TI - An investigation for public acceptance of laparoendoscopic single-site surgery.
AB - Objective : Laparoendoscopic single-site surgery (LESS) is the latest innovation
in minimally invasive surgery with unconfirmed advantages. The public perception
of LESS is the basis of carrying out the surgery. METHODOLOGY: Participants from
the outpatient department were invited to rate, on a 5-point Likert scale, the
important factors including scar, complications, cost, pain and hospital stay in
choosing surgery. In addition, those who preferred LESS would continue to make
their choices as the risks of LESS in above mentioned aspects rose. RESULTS:
About 85% of the questionnaires were included in the analysis. Complication was
the most important factor with an average score of 4.77+/-0.43, followed by pain
(3.84+/-0.96), scar (3.57+/-1.17), cost (3.41+/-0.87) and hospital stay (3.04+/
0.86). Of the 196 participants, 132 (67%) preferred LESS with younger age (35.3+/
10.64 versus 40.4 +/-9.6, P=0.001). Better cosmesis was the only factor that made
the participants choose LESS (3.78+/-1.11 versus 3.13+/-1.19, P<0.005). Almost
90% of the participants could accept the hypothesis (incision length of 3.5cm,
cost up to 120%, pain up to 120%, hospital stay of 5 days), while only 50% of
participants could accept the risk of complications of 6%. CONCLUSIONS:
Complication is the most important factor that the public are concerned about in
choosing surgery. LESS is preferred by young who care more concerned about the
cosmesis, even with moderately elevated risks of extending incision and
increasing hospital cost, postoperative pain and hospital stay.
PMID- 24353616
TI - Comparison between Double J (DJ) Ureteral Stenting and Percutaneous Nephrostomy
(PCN) in Obstructive Uropathy.
AB - OBJECTIVE: To compare the complications rate of percutaneous nephrostomy and
double J ureteral stenting in the management of obstructive uropathy.
METHODOLOGY: Total number of 300 patients of age 20-80 years who underwent JJ
stenting or percutaneous nephrostomy for obstructive uropathy were included in
this study. Patients were divided in two groups i.e. A & B. In group A, 100
patients who underwent double J ureteral stenting while in group B, 200 patients
who underwent percutaneous nephrostomy tube insertion were included. The stent
was inserted retrograde by using cystoscope, under mild sedation or local
anesthesia. While the percutaneous nephrostomy was done under ultrasound guidance
by using local anesthetic agent. Complications were noted in immediate post
operative period and on follow up. RESULTS: Majority of the patients were between
36 to 50 years of age with male to female ratio was 2.6:1. The most common cause
of obstructive uropathy was stone disease i.e. renal, ureteric or both. Post DJ
stent, complications like painful trigon irritation, septicemia, haematuria and
stent encrustation were seen in 12.0%, 7.0%, 10.0% and 5.0% patients
respectively. On the other hand, post-PCN septicemia, bleeding and tube
dislodgment or blockage was seen in 3.5%, 4.5% and 4.5% respectively. In this
study, overall success rate for double J stenting was up to 83.0% and for
percutaneous nephrostomy (PCN) was 92.0% (p<0.0001). CONCLUSION: Percutaneous
nephrostomy is a safe and better method of temporary urinary diversion than
double J stenting for management of obstructive uropathy with lower incidence of
complications.
PMID- 24353617
TI - Risk assessment of patients with diabetes for foot ulcers according to risk
classification consensus of International Working Group on Diabetic Foot (IWGDF).
AB - OBJECTIVE: The aim was assessment of diabetic foot ulcer risk factors according
to International Working Group on the Diabetic Foot (IWGDF) consensus.
METHODOLOGY: All referred patients with diabetes were divided into four groups
based on IWGDF criteria (without neuropathy, with neuropathy, neuropathy with
deformity or vascular disorders, foot ulcer or amputation history). RESULTS: Mean
age of patients was 53.8+/-10.7 years. Two hundred and sixty nine patients
(62/6%) were female and 161(37/4%) were male. Twenty three percent had disturbed
sense of vibration, 26% had decreased sensitivity to monofilaments and 17% had
decreased pain sensation. Ankle brachial index (ABI) was abnormal in 6%. About 7%
had history of prior ulcer. Patients were classified into four risk groups
according to IWGDF criteria. Two hundred and seventy seven patients (65%) were in
group 0, 75(17%) in group 1, 47 (11%) in group 2 and 31 (7%) in group 3. Patients
in higher-risk groups had higher age, longer diabetes duration, higher HbA1C and
less training (p=0.0001, 0.001, 0.0001, 0.021 respectively). The risk was higher
in the presence of retinopathy (p=0.005). Patient's sex, BMI, smoking and
nephropathy did not have significant correlation with risk of diabetic foot
ulcer. CONCLUSION: This study showed that increase of age, duration of diabetes
and HbA1c, lack of training and presence of retinopathy increases the risk of
diabetic foot ulcers.
PMID- 24353618
TI - Association between neurological and rheumatological manifestations in vitamin D
deficiency and vitamin D levels.
AB - OBJECTIVE: We aimed to investigate the associations between the neurological
manifestations of vitamin D deficiency and bone profile as well as the levels of
25-hydroxyvitamin D. METHODOLOGY: We conducted a case series on patients with
vitamin D deficiency who were followed up at King Abdulaziz Medical City, Jeddah
between January 2010 and December 2011. We collected patients' demographic data
and gathered information on etiological factors for vitamin D deficiency as well
as clinical presentations (typical, neurological and rheumatological) and
radiological findings. The t-test was used to determine whether there was an
association between the neurological manifestations of vitamin D deficiency and
vitamin D levels and bone profile. RESULTS: We enrolled 60 patients with vitamin
D deficiency. Of these, 44 (73.3%) had neurological presentations, namely
progressive muscle weakness and proximal weakness, which was observed more often
than distal weakness. In addition, gait disturbances were observed in 61.7% of
all patients with neurological and rheumatological presentations. There was no
significant association between neurological and rheumatological manifestations
and bone profile or vitamin D levels. We found a significant association between
difficulty in walking and the levels of serum calcium and phosphate (P = 0.043
and 0.037, respectively). CONCLUSION: Neurological and rheumatologic
manifestations of vitamin D deficiency are not associated with 25-hydroxyvitamin
D levels or bone profile.
PMID- 24353619
TI - Are rural South African children abdominally obese?
AB - OBJECTIVES: While available data exist on total body fat of rural South African
children, as measured by body mass index, little is known concerning the
abdominal obesity of rural South African children. The aim of this study was to
determine the prevalence of abdominal obesity among rural South African children.
Methods : Participants involved 1 172 rural black school children (541 boys and
631 girls) aged 10-16 years, residing in Mankweng and Toronto, both rural black
settlements in Capricorn district, Limpopo province, South Africa. Height, weight
and waist circumference were measured using standard techniques. Waist-to-height
ratio (WHtR) was calculated. A WHtR <= 0.50 was used to determine abdominal
obesity. Results were analysed using student t-test and Chi-squared statistics,
with a p-value of < 0.05. Results : Waist-to-height ratio showed inconsistent
results in both sexes and across age groups, with no significant differences
among boys and girls in all age groups. The proportion of boys with a WHtR >= 0.5
was 69 (12.8%), while girls were 92 (14.6%). The highest proportion of WHtR
occurs at age 11 in boys, while this proportionality increases with age in girls,
peaking at ages 14-16 years. Overall, 161 (13.7%) children had central obesity.
Conclusions : This study indicates that abdominal obesity as measured by WHtR is
prevalent among rural black South African children. The prevalence of WHtR >= 0.5
(13.7%) among the children is worrisome, as its signals the presence of obesity
related problems and the likely susceptibility of these sample children to future
health risks. Therefore, interventions strategies are needed to reduce central
obesity among children.
PMID- 24353620
TI - Improvement in JOA Score of Treatment for Complex Atlas-Axis fractures.
AB - OBJECTIVE: The aim of this study was to explore the role of treatment for complex
Atlas-Axis fractures, and compare the JOA score of surgical and conservation
methods. METHODOLOGY: From June 2008 to May 2012, 33 patients suffering from
Atlas-Axis fracture were included in our study. Fifteen patients received
posterior cervical pedicle screw fixation, and 18 patients received the
conservation treatment. All the patients were followed up for 12 months after
discharge. RESULTS: The mean operative time was about 128 minutes (ranged: 92 to
165 minutes), the mean hospital stay time was 15.5 days (ranged: 8-21 days), and
the mean follow-up of all the patients was 27months (ranged: 7 to 43 months). All
patients gained a solid fusion, and no one showed any disability at the end of
the follow-up. The JOA scores before treatment were 6.4+/-0.3 and 7.1+/-0.4
before and after treatment, and they significantly increased to 13.8+/-0.8 and
13.7+/-0.9 when following up for 12 months (P<0.05). CONCLUSIONS: Posterior
cervical pedicle screw fixation is a feasible, effective and safe method for
complex atlantoaxial fractures. This technique could achieve high JOA score,
decreased blood loss and post-operative complications.
PMID- 24353621
TI - Paternal factors in spontaneous first trimester miscarriage.
AB - Objectives : To determine whether paternal factors i.e., age, tobacco use and
genital tract infection increase the risk for spontaneous first trimester
miscarriage. Methodology : This case control study was conducted in the
Department of Obstetrics & Gynaecology, Unit V / IV, Dow Medical College & Lyari
General Hospital, Dow University of Health Sciences, Karachi, Pakistan. Duration
of study was two and half years, from Nov, 2007 to Apr, 2010. Inclusion criteria
were pregnant women with age 20 - 35 years irrespective of parity. Exclusion
criteria were known medical illness in either partner, induced abortion and
recurrent miscarriages. Studied paternal factors were age, tobacco use and
genital tract infection. Data was computed using SPSS version 16. Significance of
paternal factors was determined by Logistic Regression Analysis. Results : Total
cases studied were 200, while there were 400 controls. Mean maternal age was
27.6+/-4.9 years in cases and 26.5+/-4.5 years in controls. Mean paternal age was
35.5+/-6.2 years in cases and 32.3+/-5.4 years in controls. Paternal age was >35
years in 54.5% cases and 16.8% controls. Spearman Bivariate correlation revealed
paternal age > 35 years (p=0.000) and genital tract infection (p=0.043) as
significant factors. Only paternal age >35 years (p=0.000) remained significant
in Final Model after entering into logistic regression. CONCLUSION: Paternal age
beyond 35 years was found to be significantly related to first trimester
spontaneous miscarriages.
PMID- 24353622
TI - Uterine rupture revisited: Predisposing factors, clinical features, management
and outcomes from a tertiary care center in Turkey.
AB - OBJECTIVE: To determine the predisposing factors, modes of clinical presentation,
management modalities and fetomaternal outcomes of uterine rupture cases at a
tertiary care center in Turkey. METHODOLOGY: A 14-year retrospective analysis of
61 gravid (>20 weeks of gestation) uterine rupture cases between January 1998 to
March 2012 was carried out. RESULTS: The incidence of ruptured uteri was
calculated to be 0.116%. Persistence for vaginal delivery after cesarean was the
most common cause of uterine rupture (31.1%). Ablatio placenta was the most
common co-existent obstetric pathology (4.9%). Bleeding was the main symptom at
presentation (44.3%) and complete type of uterine rupture (93.4%) was more likely
to occur. Isthmus was the most vulnerable part of uterus (39.3%) for rupture. The
longer the interval between rupture and surgical intervention, the longer the
duration of hospitalization was. Older patients with increased number of previous
pregnancies were likely to have longer hospitalization periods. CONCLUSION:
Rupture of gravid uterus brings about potentially hazardous risks. Regular
antenatal care, hospital deliveries and vigilance during labor with quick
referral to a well-equipped center may reduce the incidence of this condition.
PMID- 24353623
TI - Psoralen-ultraviolet A treatment with Psoralen-ultraviolet B therapy in the
treatment of psoriasis.
AB - OBJECTIVE: To compare the conventional psoralen-ultraviolet A treatment with
psoralen-ultraviolet B therapy in the treatment of psoriasis. METHODOLOGY: We
studied 50 patients of plaque type psoriasis who were selected to receive either
conventional psoralen-ultraviolet A or psoralen-ultraviolet B treatment. RESULTS:
There was no significant difference between the two treatment groups in the
number of patients whose skin cleared of psoriasis or the number of exposures
required for clearance. Profile of side effects and disease status was also
similar after three months of follow up. CONCLUSION: Psoralen-ultraviolet B
treatment is as effective as conventional psoralen-ultraviolet A in the treatment
of psoriasis. Further long term studies are needed to assess the safety of
psoralen-ultraviolet B.
PMID- 24353624
TI - XPG is a novel biomarker of clinical outcome in advanced non-small-cell lung
cancer.
AB - OBJECTIVE: Polymorphisms in XPG were considered to contribute to the clinical
outcome of patients receiving platinum drug chemotherapy. We investigated the
impact of several potential SNPs of XPG on the efficacy of platinum-based
chemotherapy in NSCLC patients. METHODS: A total of 433 patients were
consecutively selected between Nov. 2006 and Dec. 2007, and were followed-up up
to Nov. 2011. The genotyping of six SNPs (rs2296147, rs751402, rs873601,
rs4150375, rs17655 and rs2094258) were genotyped using the Taqman real-time PCR
method with a 7900 HT sequence detector system. RESULTS: Patients carrying CT+TT
genotype of rs2296147 had a significantly longer median PFS (17.5 months) and OS
(26.8 months) than CC genotype. Hazard ratio (HR) for PFS and OS in patients with
CT+TT genotype of rs2296147 was respectively 0.73(0.51-0.97) and 0.66(0.48-0.99)
when compare CC genotype, respectively. Similarly, patients with rs2094258 AG+GG
genotype had a longer median progression time (18.4 months) and overall survival
time (27.3 months) when compared with those with AA genotype, and HRs(95% CI) for
PFS and OS were 0.44(0.34-0.78) and 0.51(0.39-0.82), respectively. CONCLUSIONS:
Our study suggests rs2296147 CT+TT and rs2094258 AG+GG genotypes contribute to
the better survival of NSCLC. Our study provides significant information on role
of prognostic value of XPG SNPs, and detecting of XPG could be used as predictive
markers toward individualizing NSCLC treatment strategies.
PMID- 24353625
TI - Detection of extended-spectrum beta-lactamases in Klebsiella pneumoniae:
comparison of phenotypic characterization methods.
AB - OBJECTIVE: Extended-spectrum beta-lactamase producing K. pneumoniae is a serious
threat to the patients. This manuscript shows the comparison of phenotypic
characterization methods used for ESBL K. pneumoniae and frequency distribution
of these isolates in various clinical samples. METHODOLOGY: Eleven different
types of pathological samples collected on various time intervals were analyzed.
K. pneumoniae were identified with API 20E system (bioMerieux) and initial
screening of ESBL K. pneumoniae was performed using the ceftazidime antimicrobial
disc. Double-disc synergy test (DDST) and CLSI confirmatory test were compared
for the phenotypic detection of ESBL K. pneumoniae. RESULTS: A total number of
214 ESBL producing K. pneumoniae were isolated from various clinical samples.
Frequency distribution of ESBL producing K. pneumoniae was found to be highest
among blood 117 (54.7%) and urine 46 (21.5%) samples. Data regarding the use of
various interventions among these patients showed most common presence of
intravenous line 209 (97.7%) and urinary catheters 46 (21.5%). Comparison of DDST
and CLSI confirmatory test showed that the DDST detected 145 (67.8%) isolates
while 213 (99.5%) ESBL K. pneumoniae were characterized by CLSI confirmatory
test. CONCLUSION: The use of CLSI confirmatory test is very efficient in the
early detection of ESBL K. pneumoniae especially when the facilities for
molecular characterization are not available.
PMID- 24353626
TI - Anti-cyclic citrullinated peptide antibody is a good indicator for the diagnosis
of rheumatoid arthritis.
AB - OBJECTIVES: Anti-cyclic citrullinated peptide (CCP) antibody has recently been
used in the classification of rheumatoid arthritis (RA). This antibody is more
specific than rheumatoid factor (RF) for the diagnosis of RA. The study
objectives were to determine the sensitivity, specificity, positive and negative
predictive values of anti-CCP in RA diagnosis. METHODOLOGY: Eighty RA patients
and 80 non-RA individuals were included in the study. Blood was collected from
both arms of study subjects and tested for anti-CCP and RF antibodies. Relevant
clinical information and laboratory profiles of the RA patients were evaluated
using patients' medical records and Integrated Laboratory Management System
(ILMS), respectively. Results : The sensitivity and specificity of anti-CCP were
35% and 100% respectively. The positive and negative predictive values were 100%
and 61%, respectively. Positive anti-CCP was found significantly associated with
multiple joint pain (p< 0.001) and hand's joints pain (p=0.01), symmetrical
joints involvement (p=0.015) and high CRP value (p<0.001). Anti-CCP was also
found to have positive association with RF (p<0.001). CONCLUSION: Anti-CCP is
highly specific for the diagnosis of RA. High positive predictive value should be
taken into consideration for effective treatment.
PMID- 24353627
TI - The role of DEK protein in hepatocellular carcinoma for progression and
prognosis.
AB - OBJECTIVE: The study aim was to explore the role of DEK in tumor progression and
prognostic of hepatocellular carcinoma (HCC). METHODOLOGY: DEK protein in 178
samples of HCC was evaluated by immunohistochemical method. Additionally, the
correlation between DEK expression and the clinicopathological features was
evaluated by x(2) test or Fisher's exact test, the survival rates were calculated
by the Kaplan-Meier method, and the relationship between prognostic factors and
patient survival was also by the Cox analysis. RESULTS: DEK protein expression
was noted in 86 cases of HCC, and 61 cases of normal liver tissues. DEK positive
rate were closely correlated with the tumor size, grade, AJCC stage and survival
rate (P<0.05, respectively). HCC with large tumor, lower grade, and late-stage,
concomitant with DEK expression, had the lowest 5-years survival rate than HCC
with above factors but without DEK expression (P<0.01, respectively). DEK
expression emerged as significant independent hazard factors for survival in HCC
(P<0.01). CONCLUSIONS: DEK could promote aggressiveness of cancer behavior, and
hence poor prognosis of the HCC. It might be an independent poor prognostic
factor and can serve as a useful new therapeutic biomarker.
PMID- 24353628
TI - Emerging Patterns in Clinico-pathological spectrum of Oral Cancers.
AB - OBJECTIVE: To correlate the clinico-pathological aspects of Oral Squamous Cell
Carcinoma (OSCC) with risk factors to determine the present status and variations
in the profile. METHODOLOGY: One hundred patients of OSCC and one hundred age and
sex matched controls were selected. Detailed demographic data, regarding age,
gender, marital status, ethnicity, religion, socio-economic status along with
habits, betel quid, tobacco chewing / smoking, alcohol and dietary habits was
recorded. Detailed oral examination was carried out for the site of involvement
and associated pathology. Histological grade was determined on microscopic
examination of Hemotoxylin & Eosin (H&E) stained slides. One hundred age and sex
matched controls were also evaluated for this study. RESULTS: Ages of patients
ranged from 25 to 80 years with mean age being 47.84 +/- 12.18(SD). Maximum cases
were detected in the fifth decade. Male: Female ratio was 2.8:1. Age in controls
ranged from 22 -73 with male to female ratio being 3.54:1. In patients, most
tumors were seen in buccal cavity (54%) followed by tongue (24%). Histologically
60% cases were well differentiated. Strong association with tobacco smoking and
chewing, betel quid and its substitutes was detected, with smoking being more
prevalent in males and betel quid in females. Significantly less number of
controls were observed to be involved in these habits, with almost half having no
such addictions. CONCLUSION: The present clinico-pathological status of oral
cancer still emphasizes primary prevention by creating awareness against the
devastating effects of tobacco use, betel quid, its substitutes and areca nut,
which can go a long way in decreasing the incidence of this disfiguring and
lethal condition.
PMID- 24353629
TI - Detection of SHV type Extended-Spectrum B-lactamase and Risk Factors in
Pseudomonas aeruginosa Clinical Isolates.
AB - OBJECTIVE: Pseudomonas aeruginosa is one of the most important causes of
nosocomial infections and can acquire resistant to many antimicrobials, including
beta-lactams. The aim of this study was to detect the prevalence of SHV type
extended-spectrum beta-lactamase (ESBL), antimicrobial resistance patterns of the
P. aeroginusa and risk factors in hospitalized patients in two teaching hospitals
in Sanandaj, Iran. METHODOLOGY: 123 P. aeruginosa were isolated from various
clinical specimens. All samples were prepared for double-disk synergy test on the
isolates for detection of ESBL. SHV was confirmed by PCR method. Risk factors
were evaluated for infection due to P. aeruginosa. RESULTS: The incidence of
multiple drug resistance (MDR) in P. aeroginusa isolates was 3.85%. The
prevalence of ESBL-SHV gene was 10.57%. Days of hospitalization (OR=14.34 CI95%
2.87-25.8), ICU hospitalization (OR=3.4 CI95% 1.24- 9.29), presence of catheter
(OR=3.63 CI 95% 1.34-9.84), use of antimicrobials within previous two weeks
(OR=5.51 CI95% 1.85-16.43) and use of ventilator (OR=3.7557 CI95%1.29-9) were
risk factors for Pseudomonas nosocomial infection SHV positive ESBL. CONCLUSION:
In this study Prevalence of ESBL, SHV gene and MDR in P. aeroginosa infection was
lower than the prevalence reported from other studies in Iran and this indicated
appropriate antimicrobial managements strategies and infection control. In
addition, our research data indicate that risk factors such as use of ventilator,
use of antimicrobials and ICU hospitalization can be effective in managing
Pseudomonas infection.
PMID- 24353630
TI - The impact of medical insurance policies on the hospitalization services
utilization of people with schizophrenia: A case study in Changsha, China.
AB - OBJECTIVE: To evaluate the impact of two medical insurers' policies on the
hospitalization of people with schizophrenia and the economic burden they faced
during a period of rapid health services reform in China. METHODOLOGY: A
comparative analysis was made of Urban Employee-Basic Medical Insurance (UE-BMI)
and Urban Residents-Basic Medical Insurance (UR-BMI) policies on the medical
management of schizophrenics, and was compared with hospitalization expenses,
insurer reimbursement data and other information collected from the HMO (health
maintenance organization) and social insurance agencies on the care of people
with schizophrenia in Changsha in 2010. In-depth interviews were also conducted
with relevant managers. RESULTS: Compared with inpatients covered by UR-BMI, the
inpatients of UE-BMI were admitted to higher level medical institutions and were
prescribed expensive second generation antipsychotics (SGA) medicines.
Nevertheless, the hospitalization service utilization and cost of inpatients'
hospitalization under UE-BMI were far less than that of inpatients under UR-BMI.
CONCLUSIONS: The insurance level difference between two medical insurance schemes
influences the treatment regimens and benefits received by patients. Furthermore,
the integration of schizophrenia management into the outpatient services pooling
fund for special diseases(OS-PFSD) can appropriately reduce hospitalization
utilization, which, together with the payment way reform and the prescription of
reasonable medications, can significantly reduce the overall hospitalization cost
for patients.
PMID- 24353631
TI - Biliary bypass surgery - Analysis of indications & outcome of different
procedures.
AB - OBJECTIVES: This study reports the indications and outcome of various biliary
bypass surgical procedures from a single centre over a period of 10 years.
METHODS: This is a prospective observational study conducted over a period of 10
years (January 2001-december 2010). A total of 1500 patients were included, who
underwent pancreatico-biliary surgery due to common bile duct (CBD) stones,
congenital anomalies of biliary tree, unoperable pancreatico-biliary
malignancies, CBD strictures and cases who developed iatrogenic biliary injuries
during cholecystectomy (both open & laproscopic) during this period of time. The
patients who required biliary bypass surgery were further analysed for
indications and outcome. RESULTS: Out of 1500 patients 83(5.53%) required biliary
bypass surgical procedures. The CBD stones were observed as the most common
indication (25.3%), followed by CBD injuries after open(10.84%) or laproscopic
cholecystectomy (14.46%), carcinoma head of pancreas (12.05%) and CBD
obstruction(14.46%) either due to CBD strictures or unknown distal obstruction.
Roux-en-Y-hepatico-jejunostomy (26.51%) was the most frequently performed
procedure, followed by choledochoduodenostomy and Roux-en-Y choledocho
jejunostomy (i.e. 25.3% and 12.05% respectively). Roux-en-Y biliary bypass
procedure was observed to be associated with better outcome in terms of rate of
complications as well duration of hospital stay. CONCLUSION: Biliary bypass
surgical procedures are the better options to restore the continuity of biliary
system in patients with iatrogenic biliary tree injuries and un-operable
pancreatico-biliary malignancy. Roux-en-Y biliary bypass procedure is safe and
problem solving method in these cases.
PMID- 24353632
TI - Symptoms and Quality of Life: Before and after stem cell transplantation in
cancer.
AB - OBJECTIVE: This study was conducted thinking that it was extremely important in
terms of the disease and treatment to assess the symptoms that may be encountered
before and after a stem cell transplantation and quality of life. METHODOLOGY: A
prospective longitudinal design was used.The study was completed in two years on
82 patients who underwent transplantation at the bone marrow transplantation
unit. Data were collected using a questionnaire, the Edmonton Symptom Assessment
Scale, and the Short Form-36 quality of life scale. RESULTS: It was observed that
the patients had low mean scores of physical and mental quality of life both
before and after transplantation; there was an increase in the mean scores of all
the symptoms and primarily of fatigue after the stem cell transplantation as
compared to before it; and the mean scores of physical and mental quality of life
further declined (p<0.05). CONCLUSION: Quality of life of patients who underwent
stem cell transplantation is adversely affected in the periods immediately before
and after transplantation. Patients' quality of life worsens as the severity of
symptoms experienced by patients increases.
PMID- 24353633
TI - 25-Hydroxyvitamin D is closely related with the function of the pancreatic islet
beta cells.
AB - OBJECTIVES: This study is to investigate the relationship between 25
Hydroxyvitamin D (25-OH-D) and pancreatic islet beta cell function under
different glucose tolerance statuses in China. METHODOLOGY: Totally, 180 patients
with type 2 diabetes mellitus (DM group), 178 patients with impaired fasting
glucose/impaired glucose tolerance (IFG/IGT group), and 160 normal control
subjects (NGT group) were included to measure their body parameters and
biochemical parameters. In oral glucose tolerance test, fasting serum 25-OH-D was
assessed by the enzyme-linked immunosorbent assay (ELISA). Homeostasis model
assessment for insulin resistance (Homa-IR), insulin acuity index (IAI), beta
cell function index (Homa-BCF) as well as secretion index (IS) were determined.
RESULTS: The levels of 25-OH-D, IAI and Homa-BCF in the DM group and IFG/IGT
group were significantly lower than that in NGT group (P < 0.05). Homa-IR in DM
group and IFG/IGT group was significantly higher than that in the NGT group (P <
0.05). Pearson correlation analysis and partial correlation analysis showed that
25-OH-D was positively correlated with fasting insulin (FINS) and Homa-BCF (P <
0.05). Multiple stepwise regression analysis showed that 25-OH-D was one of the
influential factors of pancreatic islet beta cell function in patients with type
2 diabetes mellitus. CONCLUSIONS: Our results suggest that 25-OH-D is closely
related with the function of the pancreatic islet beta cells and is one of the
influential factors of pancreatic islet beta cell function.
PMID- 24353634
TI - Pattern of presentation of cervical carcinoma at Nuclear Institute of Medicine
and Radiotherapy, Pakistan.
AB - OBJECTIVE: To find the pattern of presentation of cervical carcinoma as seen at
Nuclear Institute of Medicine and Radiotherapy, Pakistan. METHODOLOGY: This
retrospective descriptive study was conducted at the Nuclear Institute of
Medicine and Radiotherapy (NIMRA) for a period of one year from January 1(st) to
December 31(st), 2009. The clinical records of all patients diagnosed with
carcinoma of the cervix were reviewed with regard to sociodemographic and
reproductive parameters. Frequency of cervix and stage of disease at time of
presentation were recorded. The data was collected on pre-designed proforma and
analysed using SPSS Version 16 statistical package. Results : There were a total
of 56 cases (33.53%) of carcinoma of cervix who presented at NIMRA during the
study period. The mean age was 51 years. Irregular vaginal bleeding, foul
smelling vaginal discharge and post coital bleeding were the most common
symptoms. Squamous cell carcinoma corresponds to 52 (92.85%) and adeno carcinoma
to 4 (7.14%) cases. Only 8(14.28%) cases were in Stage I, while 20(35.71%),
22(39.28%) were in Stages II and Stage III respectively whilst 6(10.71%) cases
were in advanced stage (1V). CONCLUSION: Squamous cell carcinoma accounted for
92.85% of cases with mean age of 51 years, most patients 74.98% presented in
stage II, III and IV. Diagnosis at advanced stage needs implementation of large
scale educational and screening programme on national level to saves the lives of
Pakistani women.
PMID- 24353635
TI - Urinary incontinence in women: prevalence rates, risk factors and impact on
quality of life.
AB - OBJECTIVES: To determine the prevalence, risk factors of urinary incontinence
(UI) and to assess its impact on the quality of women's life. METHODS: This cross
sectional study was performed 1050 female participants aged between 20-80 years.
A questionnaire form, including the socio-demographic characteristics and risk
factors and the "International Consultation on Incontinence Questionnaire-Short
Form" were used for the data collection. RESULTS: The mean age of women was
48.80+/-11.53 years. The prevalence of UI was 44.6%. The distribution of the
types of UI was 31% stress incontinence, 47.4% urge, and 33.1% mixed type.
Although 95.5% of the women reported a negative impact on the quality of life,
admission to a health center was only 63.9%, and 64.7% of the women had not
received any medical help. The statistical analysis revealed that menopause,
constipation, hypertension, diabetes, family history and parity are associated
with UI as risk factors. CONCLUSION: We suggest that in the early diagnosis and
treatment of urinary incontinence (UI), mental, educational and psychosocial
support should be given to patients together with medical therapy.
PMID- 24353636
TI - Effect of Xeroderma pigmentosum complementation group F polymorphisms and
H.pylori infection on the risk of gastric cancer.
AB - OBJECTIVE: We conducted a case-control study by genotyping three potential
functional SNPs to assess the association of Xeroderma pigmentosum
complementation group F (XPF) polymorphisms with gastric cancer susceptibility,
and role of XPF polymorphisms in combination with H.pylori infection in the risk
of gastric cancer. METHODOLOGY: A hospital case-control study was conducted. A
total of 331 patients with gastric cancer and 355 controls were collected. Three
SNPs of XPF, XPF rs180067, rs1799801 and rs2276466, were genotyped by Taqman real
time PCR method with a 7900 HT sequence detector system. RESULTS: The gastric
cancer patients were more likely to have smoking habit, a family history of
cancer and H.pylori infection. We did not find the significant difference in the
genotype distributions of XPF rs180067, rs1799801 and rs2276466 between cases and
controls. Multivariate logistic analysis showed a non-significant decreased risk
in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allele
genotypes. The stratification by H.pylori infection was not significantly
different in polymorphisms of XPF rs180067, rs1799801 and rs2276466. CONCLUSION:
There was no evidence that polymorphisms in rs180067, rs1799801 and rs2276466
significantly affect the risk of gastric cancer. Further large sample size
studies are strongly needed to validate their association.
PMID- 24353637
TI - Pre Dialysis care and types of Vascular Access Employed in Incident Hemodialysis
Patients: A study from Pakistan.
AB - OBJECTIVE: To determine frequency of different vascular access use in Incident
hemodialysis (HD) patients and determine whether predialysis care in terms of
timely advice for vascular access placement was better in the hands of
nephrologist. METHODS: A cross sectional study was conducted. Data was collected
on the type of access used for first HD, including temporary Central venous
catheters (CVC), permanent CVC (Permacath), arteriovenous fistula (AVF), or
arteriovenous graft (AVG). In addition, information was also gathered if patients
were aware of their renal disease and was followed by other physicians or
nephrologist. RESULTS: A total of 120 patients were enrolled in the study, 80%
required CVC as their first access for HD (96/120 patients) out of which 74.2%
were dialyzed through temporary catheter and 5.8% through Permacath. About 20% of
patients were dialyzed through mature Arteriovenous (AV) access. Majority (95.8%)
of patients were being followed by any health care provider. 68% of them were
aware of their renal disease. About 55.8% were referred to nephrologist and 40%
were followed by other physicians. About 83.5% of patients followed by
nephrologist were advised AV access prior to commencing HD, compared to only
10.4% followed by other physicians (p<0.05). 24/61 (39.3%) patients that were
advised AV access by both groups had timely made AV access and underwent HD by
it. CONCLUSION: Very high incidence of temporary HD catheter was used in Incident
HD patients. Moreover, pre dialysis care in terms of placement of AV access prior
to initiating HD is better in the hands of nephrologist and patients should be
timely referred to nephrologist especially when they have Stage 4 chronic kidney
disease (CKD).
PMID- 24353638
TI - Evaluation of unintentional injuries sustained by children: A hospital based
study from Ankara-Turkey.
AB - OBJECTIVES: Unintentional injuries are one of the leading causes of death,
hospitalization and disability across the world. Detailed work on child injury in
low-income and middle-income countries began more recently and is now indicating
priorities for prevention. This study aims to draw attention to the subject with
the assessment of the injuries sustained by the study group. METHODOLOGY: Data of
the descriptive study was collected at the Emergency Department's trauma section
of a Training and Research Hospital, located in Ankara during the period of
October-November 2010. Children visiting the hospital due to an injury under the
age of 18 were included to the study group by assent of the child and consent of
the parents. RESULTS: Of the study group 75.3% were boys, 35.31% were 11-15 year
of age. The most frequent cause of the injuries were falls among boys (48.3%),
girls (50.0%) and, 11-15 years of age (32.8%). Most injured organs (63.6%) were
extremities and most frequent damage caused by the injury was fracture (29.5%).
Almost half of the injuries (44.0%) occurred in and around the school.
CONCLUSION: Development and implementation of systematic surveillance is
necessary to identify the epidemiologic characteristics of childhood injuries at
national level. Definition of the risk factors and protective factors is a
priority of countries to prevent such injuries.
PMID- 24353640
TI - Socio-demographic Risk Factors of Gestational Diabetes Mellitus.
AB - OBJECTIVE: The objective of the study was to report the socio demographic risk
factors of gestational diabetes mellitus (GDM). METHODS: This study was conducted
in the Institute of Chemical Sciences, University of Peshawar. In this study 103
GDM and 97 healthy pregnant women (HPW) were registered in Khyber Teaching
Hospital (KTH), Peshawar, Pakistan. Women with gestational diabetes were
diagnosed with 75mg Oral Glucose Tolerance Test (OGTT). Data was collected
through questionnaire which had information about sociodemographic risk factors.
RESULTS: Maternal age, BMI and parity of GDM were significantly higher at P<0.05
as compared to HPW. Previous history of gestational diabetes and family history
of diabetes of GDM women were also significantly higher at P<0.001 as compared
the control group. Socioecnomic status, education level and occupations of GDM
and HPW were not significantly different. CONCLUSION: Maternal age, BMI, parity,
previous history of gestational diabetes and family history of diabetes are the
high risk factors of GDM. Socioecnomic status does not affect the prevalence of
GDM.
PMID- 24353639
TI - Efficacy of linezolid on gram-positive bacterial infection in elderly patients
and the risk factors associated with thrombocytopenia.
AB - Objective : Linezolid is active against drug-resistant gram-positive bacteria.
However, the efficacy and safety of linezolid in the treatment of the elderly
have not been well characterized. The purpose of this study was to evaluate the
efficacy of linezolid in the treatment of the elderly with gram-positive
bacterial infection and to investigate the risk factors associated with the
development of thrombocytopenia in these patients. METHODOLOGY: This was a
retrospective analysis of 50 elderly patients who were treated with intravenous
linezolid for gram-positive bacterial infection. Clinical data and
bacteriological responses were assessed. Risk factors associated with
thrombocytopenia in elderly patients were analyzed. RESULTS: The overall clinical
cure rate of linezolid was 74%, and the bacteriological eradication rate was 69%.
Thrombocytopenia occurred in 24 patients, and thrombocytopenia was associated
with both the duration of treatment (P = 0.005) and the baseline platelet count
(P = 0.042). Based on a logistic regression analysis, the baseline platelet count
<200*10(9)/L (OR = 0.244; 95% CI = 0.068- 0.874; P = 0.030) was identified as the
only significant risk factor for linezolid-associated thrombocytopenia in elderly
patients. The mean platelet count decreased significantly from the 7(th) day of
treatment, and decreased to the lowest value 1-2 days after the end of therapy.
Conclusions : Linezolid is effective and safe for the elderly with gram-positive
bacterial infections. Adverse effects such as thrombocytopenia are of greater
concern. Platelet counts should be monitored in patients who are treated with
linezolid and that measures should be taken in advance to avoid hemorrhagic
tendencies.
PMID- 24353641
TI - Efficacy of treatment with glucosamine sulfate in patients with knee effusion due
to osteoarthritis.
AB - OBJECTIVE: Evaluation of anti-inflammatory effect of Glucosamine sulfate (GS)
versus diclofenac sodium (DS) in effusion of osteoarthritic knees. METHODOLOGY:
In this study, patients were included in this study from 2007-2010 based on
American College of Rheumatology criteria with OA and physical examination in
effusion of osteoarthritic knees. The patients were divided into two groups.
First group (27 patients) DS was given in doses 75 mg twice daily for ten day. In
the group II (25 patients) GS was used in doses of 1500 mg two times daily over
the first 12 weeks of the study. A closed aspiration was performed. The knee
circumference was measured in patients before and 12 week after treatment. Before
and after 12 weeks of treatments, both groups of patients were assessed according
to the WOMAC questionnaire of knee pain and function scores. RESULTS: Comparison
of knee mean circumference between the two groups was not statistically
significant before treatment (p=0.938), but significant after treatment
(p<0.001). At the end of the 12 week, there was 66.6% complete resolution of
effusion in the DS group (18 patients) and 24.0% (6 patients) in the GS group,
this was statistically significant (P<0.001). DS groups, results of the beginning
and at the end of 12 week measurement showed significant differences in WOMAC
pain mean score (P < 0.001) but GS groups not statistically significant
(P=0.160). The WOMAC function mean scores in pre and post-treatment periods of
follow-up showed significant variation between the two groups (P< 0.001,
P<0.001). CONCLUSIONS: Our observations suggest that GS is not able to suppress
the progression of adjuvant arthritis in OA with effusion of knee osteoarthritis.
GS should not be expected as anti-inflammatory influence as DF in the treatment
of OA-related effusion.
PMID- 24353642
TI - Antimicrobial susceptibility pattern of aerobic microbial isolates in a clinical
laboratory in Karachi - Pakistan.
AB - Backgroun and Objective: Resistance to multiple antimicrobials is the major cause
of debility and death due to infectious diseases around the world. Our objective
was to determine the frequency and antimicrobial susceptibility pattern of
aerobic microbial isolates in a clinical laboratory. METHODOLOGY: All culture
specimens of tissue, pus, urine, bone, blood, fluid, stool, sputum, and high
vaginal swab received in the Microbiology Department of Clinical & Research
Laboratory, Baqai Institute of Diabetology and Endocrinology from May 2010 to
January 2011 were included in the present study. Bacterial isolates were
identified and their antimicrobial susceptibility pattern was determined.
RESULTS: Out of 312 cultured specimens, 272 (87.17%) were found infected with 437
microbial organisms (412 bacteria and 25 Candida isolates). A total of 90
(20.59%) multi-drug resistant (MDR) isolates were found. MDR Escherichia coli was
isolated in 40 (34.19%) out of 117 culture specimens which showed the growth of
Escherichia coli, Pseudomonas aeruginosa in 17 (22.08%), Methicillin-resistant
Staphylococcus aureus in 13 (11.50%), Klebsiella pneumoniae in 7 (22.58%),
Proteus species in 6 (31.58%), Acinetobacter species in 3 (33.33%), Enterobacter
species in 2 (28.57%), Coliform (Escherichia coli) in 1 (16.67%) and Enterococcus
species were isolated in 1 (50%) culture specimen. CONCLUSIONS: High prevalence
of multi-drug resistant bacteria was found in the present study. Emergence of
antimicrobial resistance has become a major challenge in infectious disease
medicine. Antimicrobial resistance may be due to misuse of antimicrobials by
physicians and self medication in Pakistan. Further large scale studies are
needed to validate our findings.
PMID- 24353643
TI - Case series of syphilis and HIV co-infections.
AB - Syphilis and HIV co-infection are indeed dangerous combinations. The present
communication describes three different cases of syphilis and HIV co-infection in
young men. The first case is a 25-year-old medical graduate with a primary and
secondary syphilis lesions at time of presentation. The second case is a 24-year
old government officer with right eye posterior uveitis where the serology tests
for syphilis were reactive. His HIV tests were also positive. The final case is a
25-year-old homosexual who was admitted to the medical ward because of
Mycobacterium tuberculosis infection. The HIV and syphilis serology tests were
noted to be positive.
PMID- 24353644
TI - Encephalitis followed by optic neuritis: a case report and review of literature.
AB - Encephalitis has been included in the causes of optic neuritis, but post
encephalitic optic neuritis has been rarely reported. Majority of the cases of
optic neuritis are either idiopathic or associated with multiple sclerosis,
especially in western countries. This is very important in the Asian population
where the incidence and prevalence of multiple sclerosis is not as high as in the
Western countries. Although post infectious optic neuritis is more common in
children, it can also be found in adults and is usually seen one to three weeks
after a symptomatic infective prodrome. Here, we present a case of a 48 year-old
male who developed optic neuritis following viral encephalitis. His first
presentation was with severe headache of two weeks duration. Viral encephalitis
was diagnosed and treated. The patient presented again three weeks later with
right eye pain and other features typical of optic neuritis. Corticosteroid
therapy facilitated prompt recovery. Optic neuritis is an uncommon manifestation
of encephalitis. It is important that both doctors and patients remain aware of
post infectious cause of optic neuritis, which would enable a timely diagnosis
and treatment of this reversible cause of vision loss.
PMID- 24353645
TI - Migration of fully deployed stent after intracoronary glyceryl trinitrate
administration: An unusual percutaneous coronary intervention complication.
AB - Stent embolization is a rare complication of coronary stenting. If left
untreated, it may lead to devastating consequences. Although there is much known
about stent embolization, data about migration of stent after deployment is
limited. We report an unusual case of a deployed stent migration into the distal
part of right coronary artery after intracoronary glyceryl trinitrate
administration during percutaneous coronary intervention.
PMID- 24353646
TI - Omphalomesenteric duct cyst in an omphalocele: a rare association.
AB - Omphalomesenteric duct (OMD) remnants and omphalocele are not infrequently seen
in paediatric patients. In most of the cases, OMD remnant in an omphalocele is a
Meckel's diverticulum; however rarely there may be other lesions. A one-day old
male baby underwent surgery for omphalocele. At exploration a 10 x 12 cm cyst
containing gut contents was found as the content of the omphalocele, with
proximal and distal ileal loops running in continuity with it. Resection of the
cyst with end to end primary gut anastomosis was done. Baby also had complex
associated cardiac anomalies and died few days after surgery due to sepsis.
PMID- 24353647
TI - Occluded middle cerebral artery vascular stump mimicking aneurysm: case report
and review of literature.
AB - The stump of an occluded middle cerebral artery (MCA) is a rare but important
aneurysm mimic. A 57-year-old male was admitted due to recurrent onset of
transient ischemic attack. Computed tomography angiography (CTA) and digital
subtraction angiography (DSA) showed a total obstruction in the right MCA with
moyamoya phenomenon at distal trunks and a protruding lesion in the left MCA
bifurcation. The patient was diagnosed with left MCA bifurcation aneurysm.
Intraoperatively, the lesion was found to be an occluded right MCA stump.
Encephalomyoarteriosynangiosis was performed, and the patient remained symptom
free at the 6-month follow-up. The possibility of a vascular stump should be
considered when an aneurismal lesion is present at the MCA bifurcation with
moyamoya phenomenon at distal trunks.
PMID- 24353648
TI - Anaplastic Solitary plasmacytoma of mandible, masquerading as sarcoma.
AB - Plasma cell neoplasm is characterized by a monoclonal neoplastic proliferation of
plasma cells and solitary plasmocytoma of bone (SPB) is a localized form. It
usually occurs in vertebrae and secondarily in long bones. Its presence in
mandible is extremely rare event. A 48-year-old man consulted to our clinic with
a chief complaint of pain in his mandible. Radiography revealed a destructive
lesion in body and ramus. The initial pathologic evaluation revealed a high grade
pleomorphic neoplasm. The diagnosis was confirmed by immunohistochemical markers.
Overall, plasmacytoma with anaplastic features can be confused with high grade
sarcoma clinically and histologically.
PMID- 24353649
TI - Lumbar hernia associated with chronic obstructive pulmonary disease (COPD).
AB - Lumbar hernias are very rare posterolateral abdominal wall hernias, and they are
spontaneous in most adult patients. Here we report two cases of spontaneous
lumbar hernias associated with chronic obstructive pulmonary disease (COPD). Some
factors such as chronic cough, poor nutritional status and old age in patients
with COPD would contribute to lumbar hernia.
PMID- 24353651
TI - A meta-analysis on the EBV DNA and VCA-IgA in diagnosis of Nasopharyngeal
Carcinoma.
AB - OBJECTIVE: We conducted a meta-analysis to compare the EBV DNA and VCA-IgA in
diagnosis of Nasopharyngeal Carcinoma, and provide important evidence for
screening method of NPC. METHODOLOGY: Three databases, Medline (from Jan. 1966 to
Jan. 2012), EMBASE (from January 1988 to Jan. 2012) and Chinese Biomedical
Database (from January 1980 to Jan. 2012) were used to detect the role of EBV DNA
and VCA-IgA in diagnosis of NPC. Meta-DiSc statistical software was used for
analysis. RESULTS: Twenty seven case-control and cohort studies were included in
final analysis. A total of 1554 cases and 2932 controls were included in our meta
analysis. The Sensitivity specificity, positive likelihood (+LR) and likelihood
negative (-LR) of EBV-DNA in diagnosis of NPC were 0.75(0.72-0.76), 0.87(0.85
0.88), 6.98(4.50-10.83) and 0.18(0.11-0.29), respectively, and they were
0.83(0.81-0.85), 0.85(0.83-0.86), 10.89(5.41-21.93) and 0.20(0.14-0.29) for VCA
IgA. The SROC for EBV DNA detection was 0.939, while this was 0.936 for VCA-IgA
detection. The subgroup analysis showed EBV-DNA had larger areas under the
summary receiver operator curve when compared with VCA-IgA in high quality and
low quality studies. CONCLUSION: Our meta-analysis indicated the EBV DNA had
higher sensitivity and specificity in diagnosis of NPC.
PMID- 24353650
TI - The fiery landscape of depression: A review of the inflammatory hypothesis.
PMID- 24353652
TI - Platelet receptors; an instrumental of platelet physiology.
AB - Platelets play an important role in hemostasis, inflammation, host defense, tumor
growth and metastasis. Platelets receptors are instrumental in platelet-platelet
aggregation and interaction of platelets with leukocytes, endothelial cells and
coagulation factors. These receptors are also the targets for antiplatelet drugs.
This review focuses on the role of platelet receptors in human physiology. Data
were extracted from peer-reviewed journals using MEDLINE and EMBASE databases,
and the following terms (platelets, platelet receptors, CD markers, integrins,
tetraspanins, transmembrane receptors, prostaglandin receptors, immunoglobulin
superfamily receptors) were used.
PMID- 24353653
TI - The problem with peripherally inserted central catheters in China.
PMID- 24353654
TI - Hope and great opportunity for young neuroscientist.
PMID- 24353655
TI - Prevalence of microvascular complications in newly diagnosed patients with type 2
diabetes.
AB - BACKGROUND & OBJECTIVE: Microvascular complications are the major outcome of type
2 Diabetes Mellitus progression, which reduce the quality of life, incur heavy
economic burdens to the health care system and increase diabetic mortality. The
aims of this study were to assess the prevalence of microvascular complications
among newly diagnosed type 2 diabetic patients and to analyze the association
between these complications and poor glycemic control. METHODS: This cross
sectional hospital based study was carried out in Diabetic Clinic of Shaikh Zayed
Postgraduate Medical Institute, Lahore Pakistan. The study was conducted from
November 2011 to November 2012 among newly diagnosed type 2 diabetic patients.
Relevant information of all patients was recorded with the help of a proforma.
They were investigated for retinopathy, nephropathy and neuropathy. RESULTS: We
have divided the patients into two groups: Group I with good glycemic control
(HbA1c <6.5) and group II with poor glycemic control (HbA1c >6.5). In group II
microvascular complications were 89.8%. Neuropathy, nephropathy and retinopathy
were present in 68.5%, 56.2% and 31.4% respectively. These similar percentages in
Group I were 50%, 0% and 31% respectively and are significantly lower.
CONCLUSION: The study showed that even in newly diagnosed type 2 diabetic
patients who had poor glycemic control, frequency of microvascular complications
is much higher as compared to those who had average glycemic control. Thus tight
glycemic control does count even in newly diagnosed type 2 diabetics to prevent
and minimize the occurrence of complications.
PMID- 24353656
TI - Oxygen saturation trends in the first hour of life in healthy full-term neonates
born at moderate altitude.
AB - BACKGROUND: Transition from a parallel circulation in utero to an in-series
circulation immediately after birth is partly an oxygen-dependent process.
Relative hypoxemia with increasing altitude above sea level exerts a certain
degree of stress on oxygen-dependent metabolic processes throughout the body.
OBJECTIVE: The present study aimed to determine the reference values for oxygen
saturation and the pre-ductal and post-ductal oxygen saturation trends during the
first 60 min of life in healthy full-term neonates born at moderate altitude
(1500-2500 m) using pulse oximetry. METHODS: This descriptive study was carried
out over a period of three months started from July 2011 in the Neonatology
Department of King Abdulaziz Specialist Hospital, Taif, Saudi Arabia. In this
observational study, arterial oxygen saturation in the right hand and right foot
of each infant was recorded by pulse oximetry immediately after birth and
continuously within the first 60 min of life. The respiratory rate, heart rate,
and blood pressure were measured at birth and at 1 h after birth. Cord blood gas
and haemoglobin levels were also measured. RESULTS: The study was conducted in a
hospital situated at an altitude of 1640 m above sea level. Immediately after
birth, the mean pre-ductal SpO2 in the right hand was 68% (51-80%); in the right
foot, the mean post-ductal SpO2 was 60% (40-77%). This difference was
statistically significant (p < 0.01); however, it became statistically
insignificant at 20 min (4-45 min) and disappeared at 25 min, when the SpO2 in
both limbs equalised at 88% (83-96%). SpO2 levels > 94% were reached after 13 min
(4-35) min pre-ductally and after 22 min (10-45 min) post-ductally. The mean
respiratory rate, heart rate, and mean blood pressure at birth were 56/min,
140/min, and 34 mmHg, respectively; at 60 min, they were 40/min, 123/min, and 47
mmHg, respectively. CONCLUSION: This study defined normal range of SpO2 values in
healthy full-term neonates born at moderate altitude in the first 60 minutes of
life. These are expected to serve as base line data for normal neonates born at
similar altitudes. With regard to pre-ductal and post-ductal oxygen saturation
levels, cut-off values lower than those used at sea level should be adopted for
neonates born at moderate altitudes.
PMID- 24353657
TI - Small Endoscopic Sphincterotomy plus Large-Balloon Dilation for Removal of Large
Common Bile Duct Stones during ERCP.
AB - OBJECTIVE: This study compared the therapeutic benefits and complication rates of
small endoscopic sphincterotomy plus large-balloon dilation (ESLBD) with those of
endoscopic sphincterotomy (EST) alone for large bile duct stones. METHODS: We
compared prospectively ESLBD group (n=63) with conventional EST group (n=69) for
the treatment of large bile duct stones (>=15mm). Mechanical lithotripsy was
performed when the stone could not be removed using a normal basket. We compared
the rates of stone removal, frequency of mechanical lithotripsy use, procedure
related complications, and recurrent stones. RESULTS: A total of 132 patients
were reviewed in the study. The mean age of the patients was 67.9 years. The two
groups showed significant differences in complete stone removal during the first
session (80.9 vs. 60.8%; P = 0.046), the use of mechanical lithotripsy (7.94 vs.
24.6%; P = 0.041), and less duration of admission (P =0.045). After ERCP, there
were some instances of oozing in both groups, All patients recovered completely,
14 patients had recurrent common bile duct stones among the follow-up duration.
CONCLUSION: The ESLBD technique seems to be a feasible and safe alternative
technique for conventional EST and EBD and has no more Post-ERCP complications.
PMID- 24353658
TI - Evaluation of mobile phone addiction level and sleep quality in university
students.
AB - OBJECTIVE: To determine the mobile phone addiction level in university students,
to examine several associated factors and to evaluate the relation between the
addiction level and sleep quality. METHODS: The study is a cross-sectional
research conducted on the students of the Sakarya University between 01 November
2012 and 01 February 2013. The study group included 576 students. The Problematic
Mobile Phone Use Scale was used for evaluating the mobile phone addiction level
and the Pittsburgh Sleep Quality Index for assessing the sleep quality. Mann
Whitney U test, Kruskal-Wallis test and Spearman's Correlation Analysis were used
for analyzing the data. RESULTS: The study group consisted of 296 (51.4%) females
and 208 (48.6%) males. The mean age was 20.83 +/- 1.90 years (min:17, max:28).
The addiction level was determined to be higher in the second-year students,
those with poor family income, those with type A personality, those whose age for
first mobile phone is 13 and below and those whose duration of daily mobile phone
use is above 5 hours (p < 0.05 for each). The sleep quality worsens with
increasing mobile phone addiction level (p < 0.05). CONCLUSION: The sleep quality
worsens with increasing addiction level. It was concluded that referring the
students with suspected addiction to advanced healthcare facilities, performing
occasional scans for early diagnosis and informing the students about controlled
mobile phone use would be useful.
PMID- 24353659
TI - Effects of Cabergoline administration on uterine perfusion in women with
polycystic ovary syndrome.
AB - OBJECTIVES: The aim of this study was to determine the effects of Cabergoline
administration on uterine blood flow in women suffering from polycystic ovary
syndrome (PCOS). METHODS: This study is a randomized, controlled, triple-blind
trial which is tested on 40 women who were randomly divided into two groups of 20
people and using a randomized block design during which the subjects were
assessed and included. They were suffering from polycystic ovarian syndrome.
Inclusion criteria were classically defined PCOS criteria including:
oligomenorrhea or amenorrhea, clinical or Laboratory findings based on increase
in blood level androgen (testosterone) and ultrasound confirmation of PCOS.
Exclusion criteria were Pregnancy, lactation, Dopamine Agonist Therapy. After
selection of intervention and placebo groups, primary control Doppler ultrasound
was done for both groups. Then a weekly dose of Cabergoline 0.5 mg was
administered to intervention group for duration of 12 weeks. Placebo group were
administered placebo in the same fashion. At the end of 12 weeks, Doppler
ultrasound was performed and the results were recorded in the check lists.
RESULTS: No significant difference was noticed in both groups with respect to
their age, employment, level of education, type of infertility, duration of
marriage, and results of RI and PI before intervention. Later PCOS patients under
the treatment of Cabergoline showed a significant increase in uterine blood flow
Pulsatility Index (PI) before 2.65+/-0.52 and after 1.98+/-0.52 and RI before
0.85 and after intervention 0.77), yet no significant difference were found in
PCOS patient under the treatment of placebo. CONCLUSION: PCOS patients were shown
to have more resistance in uterine blood flow than healthy people; however,
Cabergoline administration proved to increase uterine blood perfusion and
regulate menstruation cycle.
PMID- 24353660
TI - Perception on the severity of unwanted pregnancy among university students.
AB - OBJECTIVES: The purpose of this study was to examine the perception of University
students regarding the severity of unwanted pregnancy. METHODS: This cross
sectional study involved 408 (206 females and 202 males) students residing within
the university campus. Simple and systematic sampling methods were used to select
participants. A 4-likert scaled self-administered questionnaire was used for data
collection. RESULT: Majority (87.70%) of participants perceived unwanted
pregnancy as leading to impaired mental health; 86.30% perceived it as a cause of
many other health problems; 86.60% believed it could result to shame and
withdrawal from society or even suicidal attempts; and child neglect and
abandonment (84.80%). Using the cut-off points of 75% of the total scores as a
criteria for assessing perception, fewer (60.30%) participants perceived unwanted
pregnancy as preventing a girl from continuing with her education; insufficient
money to provide for both mother and child (74.50%) and leading to higher risk of
substance abuse and problem behaviour among children born from unwanted
pregnancies (51.20%). Females students strongly agreed that unwanted pregnancy
could lead to shame and withdrawal from the society compared to their male
counterparts (Chi-square = 10.788, p = 0.013). CONCLUSION: Few students at the
University of Venda perceived unwanted pregnancy as being severe enough and
associated with truncated education, poverty for the young mother, and increased
risk of problem behaviours. Thus, intervention strategies should be instituted to
prevent unwanted pregnancies among the students.
PMID- 24353661
TI - Typhoid fever in paediatric patients in Quetta, Balochistan, Pakistan.
AB - OBJECTIVES: To determine the seropositivity of typhoid fever in febrile pediatric
patients presenting to tertiary care center. METHODS: This observational study
was conducted at Children Hospital Quetta (CHQ) from July 2011 to March 2012. The
children with three or more days fever, no obvious focus of infection and
clinically suspected of typhoid fever were screened. Sterile Blood samples were
obtained from febrile patients and Widal and Typhidot(r) tests were performed for
the diagnosis of Typhoid fever in the suspected populations. RESULTS: Total of
2964 clinically suspected patients were screened for typhoid fever. Of these, 550
(18.6%) patients were positive serologically. The higher prevalence of the
disease in hot summer season and increasing pattern of the disease was observed
in summer days. The disease was higher in school age children under 5-10 years.
Although non-significant association was observed on sex basis. CONCLUSION: The
findings highlight the considerable burden of typhoid fever in pre-school and
school-aged children. The variation in the disease pattern has also been observed
under seasonal variation and different age groups, all of which need to be
considered in deliberations to control the typhoid fever.
PMID- 24353662
TI - Comparison between coronary plaque 64-slice spiral CT characteristics and risk
factors of coronary artery disease patients in Chinese Han population and
Mongolian.
AB - Objective : To compare the coronary atherosclerotic plaque 64-slice spiral CT
characteristics and the risk factors of Han (in Inner Mongolia) and Mongolian
coronary artery disease patients. Metho d s: The plaques of 126 Mongolian and 269
Han patients were analyzed by 64-slice spiral CT coronary angiography. Their
gender, age, height, body mass, the history of hypertension, diabetes, smoking
and family diseases, the levels of triglycerides (TG), total cholesterol (TC),
high density lipoprotein cholesterol (HDL-C) and low density lipoprotein
cholesterol (LDL-C) were compared. RESULTS: The incidence of plaques (P <0.05),
the proportion of plaques in the circumflex branch (P <0.05), the proportion of
medium-severe lumen stenosis induced by plaques (P <0.05), and the proportion of
obstructive plaque involved multi-branch (P <0.05) of the Mongolian patients were
higher. The plaque compositions of the two groups did not differ significantly
(P> 0.05). The body mass index of the Mongolian patients was higher (P <0.05).
The hypertension, diabetes, smoking history, TG, TC, HDL-C and LDL-C of the two
groups did not differ significantly (P> 0.05). CONCLUSION: The higher incidence
of coronary atherosclerotic plaques and the more severe lesions of the Mongolian
patients may be related to their higher body mass index.
PMID- 24353663
TI - The relationship between the level of glutathione, impairment of glucose
metabolism and complications of diabetes mellitus.
AB - OBJECTIVE: To investigate whether there is a difference between the subjects with
new-onset type 2 diabetes mellitus (DM), impaired glucose tolerance (IGT) and
normal fasting blood glucose levels with respect to the level of glutathione
(GSH) and the relationship between the presence of complication of diabetes and
the level of GSH. METHODS: Oral Glucose Tolerance Test (OGTT) was performed in
IFG patients, with no episode of drug use, who were admitted to hospital.
According to the results of the application 30 subjects with type 2 DM, 30
subjects with IGT and 28 subjects with normal blood glucose level were included
in the study. Anthropometric measurements and blood pressure values of all
subjects were recorded. The biochemical parameters of subjects were studied in
the biochemistry laboratory by utilizing Olympus AV-2700. The subjects with
diabetic retinopathy and nephropathy were established subsequent to the
examination of the retina and 24-hour urine collection test performed to subjects
with diagnosis of DM. Levels of GSH in all subjects were measured by enzymatic
recycling method. RESULTS: The mean levels of GSH in subjects with DM were
significantly reduced compared with IGT or normal subjects (respectively p=0.02
and p<0.001). Besides, lower levels of GSH were acquired in subjects with IGT
compared to normal subjects (p<0.001). The mean levels of GSH in subjects with
diabetic retinopathy were lower than the subjects with no established diagnosis
of diabetic retinopathy (p<0.001). Similarly, lower levels of GSH (p<0.001) were
obtained in microalbuminuric subjects than normoalbuminuric subjects.
CONCLUSIONS: At the end of the study, we came to the conclusion that GSH
deficiency was of great significance in the pathogenesis of Diabetes Mellitus.
PMID- 24353664
TI - Clinical effects of surgical and Gamma Knife treatments on hippocampal sclerosis
induced intractable epilepsy of children below age 10 years.
AB - OBJECTIVE: To discuss the treatment effects and costs of surgery and Gamma Knife
on hippocampal sclerosis (HS)-induced intractable epilepsy of children below age
10 years. METHODS: The children below age 10 years who suffered from HS-induced
intractable epilepsy from June 2010 to June 2012 were subjected to surgical and
Gamma Knife treatments respectively according to their preference. RESULTS: The
short-term curative rates of the surgical group and the Gamma Knife group were
93.51% and 54.87%, respectively. The average expenses of the two groups were
10,000 CNY (Chinese Yuan) and 22,000 CNY, respectively. CONCLUSION: The two
groups were treated safely and effectively, but the surgical treatment led to
better results at a reduced cost.
PMID- 24353665
TI - Visual outcome and complications in Ab-externo scleral fixation IOL in aphakia in
pediatric age group.
AB - OBJECTIVE: To assess the visual outcome and complications in patients after Ab
externo scleral fixation of intraocular lens in pediatric age group (15 years or
less). METHODS: This quasi experimental study was conducted at Isra Postgraduate
Institute of Ophthalmology, Al-Ibrahim Eye Hospital, Karachi, from January 2012
to December 2012. All cases included were worked up according to the protocol.
All patients underwent Ab-externo scleral fixation of IOL under general
anesthesia. Patients were followed up at 1(st)day, 1(st)week, 1(st)month,
2(nd)month and 3(rd)month. Complete eye examination including best-corrected
visual acuity and complications were noted on each visit. RESULTS: Thirty
patients were included in the study, with mean age of 8.6 years (+/-3.93569).
Most of the patients, 20 (66.7%), had visual acuities of 6/18 or better. No
complication was seen in 18 (60%) of the patients intra operatively while soft
eye was observed in 7 (23.3%) of the patients. Another complication noted was
vitreous hemorrhage, which was seen in 5 (16.7%) patients. Most common post
operative complication was Uveitis followed by astigmatism. Lens dislocation and
iris abnormalities were seen in only one patient. Most of the patients showed
significant visual improvement after surgery. CONCLUSION: Ab-externo scleral
fixation of an IOL was found to be safe and showed favorable postoperative
results with fewer complications.
PMID- 24353666
TI - Awareness and use of the Canadian computed tomography head rule for mild head
injury patients among Chinese emergency physicians.
AB - OBJECTIVE: Computed tomography (CT) scan has been an increasingly essential
diagnostic tool for emergency physicians (EPs) to triage emergency patients.
Canadian computed tomography Head Rule (CCHR) had been established and widely
used to spare patients with mild head injury from unnecessary radiation. However,
the awareness of CCHR and its actual utilization among Chinese EPs were unknown.
This survey was to investigate the awareness and use of CCHR and their associated
characteristics among Chinese EPs. METHODS: Questionnaire was randomly sent to
EPs from different Chinese hospitals. Surveyed EPs were asked how well they know
about the CCHR and how often they use the CCHR to guide head CT use. Association
between the awareness and utilization of CCHR and the physicians' characteristics
were analyzed using repeated-measures logistic regression. RESULTS: About 41.7%
of the total 247 responders noted they "very familiar" or "somewhat familiar"
with CCHR while the utilization rate was 24.7%. With respect to the most
important underlying barriers for the use of CCHR, approximate half (48.5%) cited
"fear of malpractice" as the leading cause. "Received specific training regarding
radiation dose of CT" was the significant predicting factor both for the
awareness (OR 5.87; 95% CI, 3.08-11.21) and the use (OR 6.10, 95% CI, 2.91-12.80)
of CCHR. CONCLUSIONS: Fear of malpractice and lack of radiation risk knowledge
were two main barriers to apply CCHR in the request of CT for patients with mild
head injury. Furthermore, EPs with specific training about radiation risk of CT
were more likely to know and use of CCHR.
PMID- 24353667
TI - A novel multiplex PCR for detection of Pseudomonas aeruginosa: A major cause of
wound infections.
AB - BACKGROUND AND OBJECTIVE: Wound infections are often difficult to treat due to
various bacterial pathogens. Pseudomonas aeruginosa is one of the common invaders
of open wounds. Precise diagnosis of this etiological agent in wound infections
is of critical importance particularly in treatment of problematic cases. The
existing diagnostic methods have certain limitations particularly related to
specificity. Our objective was to to establish a comprehensive and reliable
multiplex PCR to confirm diagnosis of P. aeruginosa. METHODS: A multiplex PCR
test was developed for rapid and comprehensive identification of P. aeruginosa.
Four highly specific genes were targeted simultaneously for detection of genus,
species and exotoxin production (16S rDNA, gyrB, oprL and ETA) in P. aeruginosa;
additionally one internal control gene (invA) of Salmonella was used. The
specificity of the multiplex PCR was confirmed using internal and negative
controls. Amplified fragments were confirmed by restriction analysis and DNA
sequencing. RESULTS: The developed method was applied on 40 morphologically
suspected P. aeruginosa isolates (from 200 pus samples) and 18 isolates were
confirmed as P. aeruginosa. In comparison, only 12 could be identified
biochemically. CONCLUSIONS: Combination of the four reported genes in multiplex
PCR provided more confident and comprehensive detection of P. aeruginosa which is
applicable for screening of wound infections and assisting treatment strategy.
PMID- 24353668
TI - Investigation of features of patients in renal transplantation waiting list: Who
wants much more of what for renal transplantation?
AB - BACKGROUND AND OBJECTIVE: Renal transplant is the best form of treatment for most
patients with end-stage renal disease (ESRD), because that therapy improves
quality of life, prolongs survival, and is cost-effective. The objective of the
study being reported was to compare the sociodemographic characteristics and
registration status for renal transplantation of ESRD patients in Turkey who were
registered for transplant or not. METHODS: The study was conducted between June
and September 2012 on patients of several Dialysis Centers. They all were
informed in a one on one interview about the risks and benefits of renal
transplants; they were also asked to fill out the questionnaires given to them.
The study questionnaire was designed with the help of already published reports
to include among others the patient's age, sex, waiting time and educational
status. RESULTS: Patients who had been registered in the cadaver kidney waiting
list were aged 43.85+/-13.48 in the average, with a balanced sex ratio, average
dialysis duration 57.30+/-51.46 months. Of these patients 45 had finished high
school, 87 lived in rural areas and 67 had an income equivalent to expenses.
CONCLUSION: There was a significant difference among the groups depending on the
patients' residence in an urban or rural environment. Such a difference might be
following the greater ease of obtaining relevant information in the urban areas.
PMID- 24353669
TI - Knowledge and psychomotor skills of nursing students in North Cyprus in the area
of cardiopulmonary resuscitation.
AB - Objective : The aim of the study was to determine the cardiopulmonary
resuscitation (CPR) knowledge and skill levels of nursing students in North
Cyprus. Methods : The study design was quasi-experimental and longitudinal. A
questionnaire was applied to the students before the CPR lecture. Then the
students were informed about adult CPR by the researchers and all of the students
practiced CPR on a Resusci-Anne manikin. One and six months after this training
the same questionnaire and skills checklist of CPR were applied. Results : Eighty
three third year students of nursing participated in the study. While the average
CPR knowledge score of these students was 9.3 +/- 2.9 out of 23 before the
lecture, this average increased to 17.0 +/- 1.8 one month after the CPR lecture
and decreased by two points back to 14.9 +/- 3.8 after six months. Skill score of
the students one month after the CPR skills training was 18.4 out of 21, and that
this average decreased to 13.8 after six months (p<0.05). CONCLUSION: Nursing
students tend to forget theoretical and applied CPR training after couple of
months. Hence there is a need for continuous CPR training and education and
repeating the skills at regular intervals even after they have graduated to
ensure sustainability in the CPR skills.
PMID- 24353670
TI - Risk factors and complications of puerperal sepsis at a tertiary healthcare
centre.
AB - OBJECTIVE: To determine the risk factors and complications of puerperal sepsis.
METHODS: This was an observational prospective Cohort study conducted from
January 2011 to December 2011 at the Obstetrics and Gynaecology Department
Liaquat University of Medical & Health Sciences Jamshoro/Hyderabad, Sindh
Pakistan. During this study period, all the women who delivered in this hospital
or referred to this hospital within 42 days after delivery with puerperal
pyrexia/sepsis diagnosed on clinical examination as well as with relevant
investigations were included in the study. Women with other ailments like
malaria, typhoid fever and postpartum eclampsia during the puerperal period were
excluded. The subjects were registered on predesigned proforma after giving
informed written consent. The data was collected and analyzed using SPSS version
17. RESULTS: During this period there were 3316 obstetrical admission and out of
these 129(3.89%) women had puerperal sepsis. Most of these women 84(65.11%) were
aged 31 years and above, multiparous 101 (78.29%), and unbooked 98 (75.96%)
cases. Common risk factors found were absent membranes in 108(83.72%) of the
women, delivered or undelivered and mismanaged, referred cases 95(73.64%), are
being delivered in this hospital 34(26.35%). Morbidities seen were septicemia in
35 (27.13%) cases, and disseminated intra vascular coagulation in 23(17.82%)
cases, while 11 (8.52%) of the women died. CONCLUSION: Common risk factors were
anaemia; suboptimal personal hygiene as well as improper sterilization which
resulted in severe health hazards such as septicemia, disseminated intravascular
coagulation as well as death.
PMID- 24353671
TI - A new nasal cavity nursing methods application in patients with mechanical
ventilation.
AB - OBJECTIVE: To compare different nasal cavity nursing methods on mechanically
ventilated patients. METHODS: According to acute physiology and chronic health
evaluation (APACHEII), 615 cases of mechanically ventilated patients were divided
into group A, group B and group C by stratified random method. Traditional oral
nursing plus aspirating secretions from oral cavity and nasal cavity q6h were
done in group A. Based on methods in group A, normal saline was used for cleaning
nasal cavity in group B. Besides the methods in group A, atomizing nasal
cleansing a6h was also used in group C. Incidence rate of Ventilator-Associated
Pneumonia (VAP) and APACHE II scores after administrating were compared. The
correlation between APACHE II score and outcomes was analyzed by Spearman-rank
correlation. RESULTS: In group A, incidence of VAP was 36.76%, group B was
30.24%, group C was 20.38%, and the difference was statistically significant.
APACHE II scores in group C were significantly lower compared with group A and B.
APACHE II score was negatively correlated with clinical outcomes. CONCLUSIONS:
For mechanically ventilated patients, nasal nursing can't be ignored and the new
atomizing nasal cleaning is an effective method for VAP prevention.
PMID- 24353672
TI - Comparing the effect of two different intraocular lenses on optical aberrations
in bilaterally operated eyes for cataract.
AB - OBJECTIVE: To assess high order and spherical aberrations results of hydrophobic
acrylic AMO Sensar AR40E and hydrophobic acrylic Alcon AcrySof SA60AT intraocular
lenses after implantation in cases with bilateral cataract. METHODS: Cases
diagnosed as bilateral cataract were included in the study and preoperative
aberration measurements were recorded by using Nidek OPD SCAN-ARK 1000. Groups
were created by implanting AMO Sensar AR40E to one eye of the patients, while
Alcon AcrySof SA60AT into the other in a prospective and randomized manner.
Aberration measurements were recorded after one and two months of surgery.
RESULTS: Overall, 40 eyes in 20 patients (11 women and 9 men) were included in
the study. All patients underwent bilateral phacoemulsification surgery due to
cataract. There were 20 eyes in both groups. Mean age was 62.4 (range: 31-82)
years. There was no significant difference in aberrations recorded before surgery
and one and two months after surgery in both groups. (p<0.05). CONCLUSION: There
was no difference among spherical intraocular lenses used in this study.
PMID- 24353673
TI - Comparison of gestational diabetes mellitus and pre-eclampsia in women with high
hemoglobin in the first trimester of pregnancy: A longitudinal study.
AB - OBJECTIVE: To determine the association between high hemoglobin with gestational
diabetes mellitus (GDM) and preeclampsia in pregnant women in the first
trimester. METHODS: This cohort study was conducted among 973 pregnant women who
started their antenatal booking in the first trimester (first 14 weeks of
gestation). Women with first-visit high Hb levels (> 12.5 g/L) on first visit of
the pregnancy period were selected as the study group and were compared with
those who had normal Hb value (< 12.5 g/L) as controls. Adverse pregnancy
outcomes including preeclampsia and GDM were compared between the two groups.
RESULTS: Complete obstetric records of 448 women with high Hb levels and 486
women with normal Hb levels were studied. The follow up showed that the women
with high Hb levels had significantly higher rates of preeclampsia and GDM than
those with normal Hb levels; the risks were 5.4 (95% cl; 2.8 to 10.5) and 3.7
(95%cl; 2.2 to 6.4), respectively. CONCLUSION: This study found that high Hb in
the first trimester is associated with higher risk of subsequent preeclampsia and
gestational diabetes mellitus (GDM).
PMID- 24353674
TI - Nocturnal Awakening & Sleep Duration in Veterans with PTSD: An Actigraphic Study.
AB - OBJECTIVE: To assess whether awakenings from sleep and sleep duration in Post
Traumatic Stress Disorder (PTSD) were related to demography, posttraumatic or
depressive symptoms, subjective sleep quality, and daytime sleepiness. METHODS:
Sample consisted of 23 veterans with lifetime PTSD and current sleep disturbance
not due to apnea or other diagnosable conditions. Data collection included
demography, two weeks of actigraphy, Beck Depression Inventory, Posttraumatic
Checklist, Clinical Assessment of Posttraumatic Symptoms, Pittsburgh Sleep
Quality Index, and Epworth Sleepiness Scale. RESULTS: The study revealed that
awakenings increased with younger age. Variability in awakenings also increased
with younger age (p = 0.002). More awakenings were associated with shorter sleep
duration. CONCLUSIONS: These paradoxical observations regarding younger age and
more awakening may be related to increased sleep symptoms early in the course and
then gradual waning of posttraumatic symptoms over time, since awakenings tend to
increase with age in normals (rather than decrease, as we observed).
PMID- 24353675
TI - Zinc finger X-chromosomal protein promotes growth and tumorigenesis in human
osteosarcoma cells.
AB - OBJECTIVE: To investigate the role of Zinc finger X-chromosomal protein (ZFX) in
oncogenesis of Osteosarcoma tumor. METHODS: Here, we first conducted an
expression analysis of ZFX in Osteosarcoma cell lines. Then, we constructed ZFX
specific small interfering RNA (siRNA)-lentiviral vector that is capable of
effectively inhibiting the expression of ZFX gene in human Osteosarcoma Saos-2
cells, and investigated systemically the impacts of ZFX silence on the growth and
invasive ability of the cancer cells in vitro. Furthermore, we determined the
effects of ZFX knockdown on the cell cycle distribution and apoptosis of Saos-2
cells. RESULTS: We found that ZFX inhibition resulted in significantly impaired
proliferation and colony formation as well as mitigated invasiveness of Saos-2
cells. Importantly, si-ZFX infected cells exhibited a greater portion of cells at
G1 phase, but a minor portion of S and G2/M phase cells. Moreover, a greater
portion of sub-G1 apoptotic cells was observed in si-ZFX infected cells.
CONCLUSIONS: These results strongly suggest that ZFX is a novel proliferation
regulator that promotes growth of Osteosarcoma cells, and downregulation of ZFX
expression induces growth suppression of Saos-2 cells via arrested G0/G1 phase
cell cycle and apoptosis pathways, thereby indicating that ZFX may serve as a new
molecular target for Osteosarcoma tumor therapy.
PMID- 24353676
TI - Diagnostic value of ischemia-modified albumin in acute coronary syndrome and
acute ischemic stroke.
AB - OBJECTIVE: To investigate diagnostic value of ischemia-modified albumin (IMA)
levels in patients applying to emergency with symptoms of acute coronary syndrome
(ACS) and acute ischemic stroke (AIS). METHODS: Two patient groups (ACS and AIS)
and a control group were constituted. The study was discontinued upon reaching 30
patients in each group. Following patient approval at the initial visit, a total
of 10 ml venous blood sample was obtained from all patients with a high clinical
suspicion of ACS and AIS. The Troponin I and the IMA levels were determined in
the blood samples. RESULTS: Statistically significant higher IMA values were
determined in the patient groups compared to the control group (p<0.001 for both
groups). No statistically significant correlation was found between the IMA and
the Troponin I values in the ACS and the AIS groups (p>0.05 for both groups). The
sensitivity of IMA was 83% and 87% for ACS and AIS, respectively. The specificity
of IMA was 90% and 87% for ACS and AIS, respectively. CONCLUSION: The sensitivity
and specificity values, determined according to the optimal cut-off values in the
groups demonstrated that IMA could be a useful diagnostic marker in ACS and AIS
patients.
PMID- 24353677
TI - Serum Zinc Level in Children Presenting with Febrile Seizures.
AB - OBJECTIVE: To determine the frequency of low serum zinc level in children
presenting with febrile seizures at The Children's Hospital and the Institute of
Child Health (CH/ICH) Multan. METHODS: This is an observational cross sectional
study conducted at the Department of Pediatric Medicine, The Children's Hospital
and the Institute of Child Health, Multan from September 2010 to March 2011.
Children (6 months to 6 years of age) presenting with febrile seizures who
satisfied inclusion and exclusion criteria were enrolled for the study. Cause of
fever was determined after detailed history, physical examination and relevant
investigations. Four milliliters centrifuged blood sample was preserved in acid
washed test tube. Separated serum was used to measure serum zinc level by
employing Randox kit on auto-analyzer in all cases. The outcome variable (serum
zinc level) was recorded on a predesigned proforma. RESULTS: Out of 100 enrolled
children, there were 66 (66%) male with male to female ratio of 1:0.52. Mean age
of the children was 23.97+/-14.45 months. Upper respiratory tract infection was
the most frequent cause of fever apparent in 24 children (24%) followed by
tonsillitis 17 (17%), pneumonia 16 (16%), urinary tract infection 16 (16%),
otitis media 15 (15%), and bronchiolitis 12 (12%). Frequency of low serum zinc
level was 26% in children with febrile seizures. CONCLUSION: Zinc deficiency
could be a potential risk factor for febrile seizure in children.
PMID- 24353678
TI - Equity of the essential public health service in rural china: evidence from a
nationwide survey of hypertensive patients.
AB - OBJECTIVES: To explore healthcare disparities in rural China two years after the
implementation of the Essential Public Health Service (EPHS) reform in 2009.
METHODS: A cross-sectional study was conducted by surveying 930 hypertension
patients (HPs) from different regions in rural China in 2011. The percentages of
patients using recommended four or more follow-up visits in a year were
calculated by patient socio-demographic characteristics and statistically
examined using chi-square and logistic regression to uncover disparities and
correlated factors in EPHS use. RESULTS: The rates were not significantly
different by age, gender, education, insurance status or income, but
significantly different by region and hypertension history (p<0.01). Higher rates
were also observed on patients who sought actively follow-up service at clinics,
making appointment for the next follow-up with doctors, awareness of the need of
follow-up, more satisfied with the follow-up services, and better medication
adherence (p<0.01). CONCLUSIONS: There were no disparities observed among HPs in
the use of follow-up services, suggesting that the reform has to some extent
achieved its goal in ensuring equal access to EPHS. In this regard, regional
implementation of the national policies and improvement of EPHS management at
local level should be further improved.
PMID- 24353679
TI - Primary effects of intravitreal bevacizumab in patients with diabetic macular
edema.
AB - OBJECTIVE: To evaluate the efficacy of primary intra vitreal bevacizumab (IVB)
injection on macular edema in diabetic patients with improvement in best
corrected visual acuity (BCVA) and central macular thickness (CMT) on optical
coherence tomography (OCT). METHODS: This prospective interventional case series
study was conducted at Retina Clinic, Al-Ibrahim Eye Hospital, and Isra
Postgraduate Institute of Ophthalmology Karachi. Between December 2010 to June
2012. BCVA measurement with Early Treatment in Diabetic Retinopathy Study (ETDRS)
charts and ophthalmic examination, including Slit-lamp bio microscopy, indirect
ophthalmoscopy, Fundus fluorescein angiography (FFA) and OCT were done at the
base line examination. At monthly interval all patients were treated with 3
injections of 0.05 ml intra vitreal injection containing 1.25 mg bevacizumab.
Patients were followed up for 6 months and BCVA and OCT were taken at the final
visit at 6 month. RESULTS: The mean BCVA at base line was 0.42+/-0.14 Log Mar
units. This improved to 0.34+/-0.13, 0.25+/-0.12, 0.17+/-0.12 and 0.16+/-0.14 Log
Mar units at 1 month after 1(st), 2(nd) 3(rd) injections and at final visit at 6
months respectively, a difference that was statistically significant (P>0.0001)
from base line. The mean 1mm CMT measurement was 452.9 +/- 143.1 um at base line,
improving to 279.8 +/- 65.2 um (P<0.0001) on final visit. No serious
complications were observed. CONCLUSIONS: Primary IVB at a dose of 1.25 mg on
monthly interval seems to provide stability and improvement in BCVA and CMT in
patient with DME.
PMID- 24353680
TI - Correlation of blood pressure and the ratio of S1 to S2 as measured by esophageal
stethoscope and wireless bluetooth transmission.
AB - Objective : Esophageal stethoscope has the advantage of being non-invasive,
easily placed and capability to monitor the heart sound. This study was designed
to determine whether the ratio of S1 to S2 analyzed by esophageal stethoscope and
wireless bluetooth transmission can be accurate indicator that express the
correlation with blood pressure. METHODS: Total 33 adult male and female without
cardiac disorder and with normal heart rhythm were selected randomly as the
subjects of this Study. Two microphones were used with one for acquisition of
heart sound by connecting it to the esophageal stethoscope while the other was
used to measure the background noise in the operating room. After having
transmitted the heart sound measured with the esophageal stethoscope to the
receiver by using bluetooth module, it was saved in PC and outputted, following
removal of noise in the operating room and the respiratory sound. S1 and S2 were
measured with computation of the ratio of S1 to S2. Correlations between the
systolic blood pressure with each of the S1, S2 and ratio of S1 to S2 were
examined by using correlation analysis. RESULTS: The ratio of S1 to S2 displayed
the highest correlation with the systolic blood pressure, with S1 and S2 also
displaying positive correlation with the systolic blood pressure. CONCLUSION: As
the result of analysis of the heart sound and the systolic blood pressure
measured by using the esophageal stethoscope, the radio of S1 to S2 displayed
greater correlation with the systolic blood pressure in comparison to the S1.
PMID- 24353681
TI - Role of laparoscopy in peritonitis.
AB - OBJECTIVE: Laparoscopy has gained clinical acceptance in many subspecialties in
the last decade. The conventional open surgery for peritonitis carries
significant morbidity and mortality. The present study was done to extend and
evaluate benefits of minimally invasive surgery in this subset of patients.
METHODS: This was a prospective study spanning over a period of four years. All
those patients diagnosed as having peritonitis on clinical assessment and
preoperative investigations and those who were stable enough haemodynamically
were included in this study. After initial resuscitation for few hours, they
underwent diagnostic and therapeutic laparoscopy to identify the cause of
peritonitis and to confirm the pathology. All cases were done under general
anesthesia, using three standard ports at appropriate sites according to
pathology. Patients were treated by different procedures either laparoscopically
or with laparoscopic assistance after diagnosis. Operative and post operative
data was collected and analyzed. RESULTS: Ninety two cases of peritonitis
underwent diagnostic and therapeutic laparoscopy. Mean age of patient was 46.5
years. 24 patients were diagnosed as perforated duodenal, in 14 (58.3%) patients
laparoscopic suture repair was done and in 8 (33.3%) small upper midline incision
was given and perforation was repaired. Out of 32 patients having perforated
appendix, 25 (78.1%) patients laparoscopic appendectomy was done while in 7
(21.8%) perforation was dealt by laparoscopic assistance. Out of 14 patients of
ileal perforation 6 (42.8%) with minimal contamination laparoscopic suture was
applied, while in 8 (57.1%), perforated loop was brought out by making small
window and perforation was closed. All 22 patients with pelvic sepsis needed only
aspiration of pus and peritoneal lavage. Only one patient died post operatively
and 2 (2.1%) patients developed fistula. 6 (6.5%) patients developed port site
infection. CONCLUSION: Laparoscopic management is feasible, safe and effective
surgical option for patients with peritonitis due to different abdominal
emergencies in properly selected cases with higher diagnostic yield and a faster
postoperative recovery.
PMID- 24353682
TI - Association between Polymorphisms in IL-16 Genes and Coronary Heart Disease risk.
AB - OBJECTIVE: We aimed to investigate the role of polymorphisms in IL-16 genes on
the susceptibility of Coronary Artery Disease (CAD). METHODS: A total of 260 CAD
cases and 281 health controls were collected between January 2008 and November
2011. Genotyping of IL-16 rs8034928, rs3848180, rs1131445, rs4778889 and
rs11556218 was conducted by polymerase chain reaction (PCR) and matrix-assisted
laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry
technologies. RESULTS: The frequencies of rs8034928 C allele and rs3848180 G
allele in the CAD cases in CAD group were significantly higher than in controls.
Compared with rs8034928 T/T genotype, a significant higher risk of CAD was found
in C/C genotype (OR=1.87, 95%CI=1.17-3.03), and variant of rs8034928 showed a
significant increased risk of CAD in dominant (OR=1.48, 95%CI=1.04-2.10) and
recessive model (OR=1.70, 95%CI=1.10-2.67). The rs3848180 G/G was found to be
associated with risk of CAD(OR=1.79, 95%CI=1.16-2.75), and G allele carries had a
significant risk of CAD (OR=1.47, 95%CI=1.02-2.13). CONCLUSIONS: Our study
indicated that rs8034928 and rs11556218 polymorphisms are associated with CAD
risk in a Chinese population, and IL-16 gene polymorphisms may be used as a
predictor to the susceptibility of CAD.
PMID- 24353683
TI - Quality of Surgical Case Notes at Dow University Hospital according to modified
ANKLe score.
AB - OBJECTIVE: To find out quality of surgical case notes according to modified
Adjusted Note keeping and Legibility (ANKLe) score in Dow University Hospital.
METHODS: For this audit, medical records of all the patients admitted in Dow
University Hospital surgery department were reviewed from February 2012 to April
2012. The modified ANKLe score (total 24) is formed by the combination of, the
content (out of 20) and legibility (out of 4) to give an overall score out of 24.
A score of at least 20 (content score 17/20; legibility score 3/4) is considered
as acceptable. It means that a surgical record is legible and the majority of the
essential content is recorded. RESULTS: A total of 236 records were evaluated.
Overall mean +/- standard deviation (SD) of ANKLe score was 18.4+/- 2.1 out of
maximum score of 24. Content and legibility has overall mean scores of 14.4 out
of 20 and 3.9 out of 4 respectively. Only two variables, patient's name and
consultant on call were documented in 100% of records while the least documented
variable were social history 2 (0.2%). Legibility scoring system provides that
218notes out of total set of 236 notes (that is 92.4% of overall notes) have
achieved a score of 4. The benchmark of 80% was achieved in 26.1% for total ANKLe
score, 6.8% for contents and 99.1% for legibility. CONCLUSION: Overall, quality
of records is not good but legibility part scores exceptionally high.
PMID- 24353684
TI - The role of laparoscopy in suspicious abdomen pain in children.
AB - OBJECTIVE: Abdominal pain is a frequently encountered problem in children.
Suspicious right lower quadrant pains are sometimes a problem for pediatric
surgeons. In this study, we wanted to evaluate the effectiveness of laparoscopy
in diagnosis and treatment of children with suspicion of abdominal pain. METHODS:
The files of 84 patients treated with a diagnosis of suspicious right lower
quadrant peritonitis between 2005 and 2011 were investigated. Laparoscopic
exploration was performed for all cases with right lower quadrant pain where the
appendix was not seen on USG/CT and the cause of acute abdomen could not be
determined. RESULTS: In this process, 84 patients consisting of 60 (71%) females
and 24 (29%) males were included in the study. The mean age was 10.5 years (7-16
years). Appendicitis was determined during diagnostic laparoscopy in 35 (41.6%)
patients. The appendix was normal in the remaining 49 (58.3%) patients. In 36 of
these patients, gynecological diseases were encountered on pathology as the most
frequent cause of the acute abdomen. The appendix was preserved in patients where
the cause of the abdominal pain was explained. CONCLUSION: Laparoscopy can be
used in the diagnosis and treatment of patients with suspected acute abdomen that
imitates acute appendicitis and cannot be differentiated with physical
examination and laboratory methods. Delays in diagnosis and unnecessary
appendectomy will be prevented in this way.
PMID- 24353685
TI - Effects of alcohol on the morphological and structural changes in oral mucosa.
AB - OBJECTIVE: To investigate the morphological and structural changes of oral mucosa
under the influence of alcohol. METHODS: Sixty male and female specimens (42
males and 18 females) who died of chronic alcoholism were selected in this study.
The specimens (5-7 mm) were sliced by the morphological-histological detection
method, and stained by the HE and Spielmeyer (myelin staining) protocols
respectively. Then five immune peroxidase chemical reaction tests were performed.
RESULTS: 10% of the tissue sections had epithelial hyperplasia points with
hyperkeratosis and acanthosis. 90% of the sections had epithelial atrophy points
with different degrees of damage, and had moderate infiltration of lymphocytes
macrophages in the basal oral mucosa simultaneously. For the tissue sections of
patients who died of cardiovascular diseases with a history of alcoholism, about
a half showed that extensive necrotic points were observed in different parts of
oral mucosa, accompanied by a secondary infection. Approximately 15% of the
sections had more dense and homogeneous necrotic tissues with microbial
colonization, and the necrotic focus of 5% of the sections was located above the
epithelial tissue, which was not distinctively different from other tissues. 48%
of the sections were subjected to small nerve bundles with jeopardized deep oral
mucosa, accompanied by necrosis of neuron axon and its myelin membrane.
CONCLUSION: The findings of this study show that drinking alcohol over an
extended time may lead to carcinogenic changes in oral mucosa.
PMID- 24353686
TI - Gender differences in severity of sickle cell diseases in non-smokers.
AB - OBJECTIVE: To find out gender differences in severity of sickle cell diseases
(SCDs) in non-smokers. METHODS: Three groups of SCDs patients on the basis of red
blood cell (RBC) transfusions were included. Less than 10 units in their lives
were kept in Group-1, Ten units of higher in Group-2 and 50 units or higher as
the Third Group. Patients with a history of using one pack of cigarettes -year or
above were excluded. RESULTS: The study included 269 patients. Mean ages of the
groups were similar (28.4, 28.5, and 28.9 years, respectively). Prevalences of
cases without any RBC transfusion in their lives were 7.2% and 3.7% in females
and males, respectively (p<0.05). Prevalences of cases without any painful crisis
were 13.8% and 6.0% in females and males, respectively (p<0.001). There was
progressive increase according to mean painful crises, clubbing, chronic
obstructive pulmonary disease (COPD), leg ulcers, stroke, chronic renal disease
(CRD), pulmonary hypertension, and male ratio from the first towards the third
groups (p<0.05, nearly for all). Mean ages of mortal cases were 29.1 and 26.2
years in females and males, respectively (p>0.05). CONCLUSION: The higher painful
crises per year, digital clubbing, COPD, leg ulcers, stroke, CRD, pulmonary
hypertension, and male ratio of the third group, lower male ratio of patients
without any RBC transfusion, lower male ratio of patients without any painful
crisis, lower mean ages of male SCDs patients with mortality, and longer overall
survival of females in the world could not be explained by well known strong
atherosclerotic effects of smoking alone, instead it may be explained by the
dominant role of male sex in life.
PMID- 24353687
TI - Effectiveness of sodium hyaluronate eye gel in patients with dry eye disease: a
multi-centre, open label, uncontrolled study.
AB - OBJECTIVE: To assess the effectiveness of sodium hyaluronate Eye Gel in Dry Eye
Disease (DED) patients Methods: A Multi-center, Open-label, Uncontrolled clinical
trial was conducted in different centers of Pakistan. Ten ophthalmologists
conducted this study in which 250 diagnosed patients with dry eye disease were
enrolled after obtaining a written informed consent. Ten patients were dropped
out during the study period. All patients were assessed as per following criteria
for enrolling a patient into the study: Tear Film Break - up time (TBUT) <= 10
seconds, Schirmer Test - 1 <= 6 mm / 5 minutes and Positive Corneal Staining.
Tolerability/safety was assessed by the monitoring and recording of all adverse
events. The physical examination was done at baseline, 4(th) week and 8(th) week.
Results : The mean age of the patients was 43.4 +/-17.8 years and out of 240
patients 117 (48.7%) were males and 123 (51.3%) females. The Mean duration of
symptoms was 19.3+/-23.9. At the initial visit the foreign body sensation was
50.6%, itching 35.9%, burning 50.6%, watering 42.9%, photophobia 25.3% and
feeling of dryness in 14.7% of patients. After 4 weeks (2(nd) visit), the
symptoms were decreased to 47.1% foreign body sensation, 32.4% itching, 48.2%
burning, 41.8% watering, 25.3% photophobia and 13.5% feeling of dryness. At the
3(rd) visit (after 8 weeks) the frequency of symptoms were: 45.3% foreign body
sensation, 30.6% itching, 45.9% burning, 40% watering, 24.7% photophobia and
13.5% feeling of dryness. CONCLUSION: Sodium Hyaluronate can provide a suitable
alternate in the treatment of dry eye disease due to its reported efficacy on
foreign body sensation, itching, burning, watering, photophobia and feeling of
dryness.
PMID- 24353688
TI - An unusual case of silent acute ST-elevation myocardial infarction following
amphetamine use.
AB - We report a case of silent acute ST-elevation myocardial infarction associated
with amphetamine use in a 62 years old diabetic man. The patient was devoid of
chest pain and had a normal cardiac enzyme analysis at the initial presentation.
A routine electrocardiogram demonstrated acute inferior wall ST-elevation
myocardial infarction. Coronary angiography confirmed a total occlusion of the
posterior lateral branch of right coronary artery. The patient underwent
successful percutaneous transluminal coronary angioplasty with stent placement.
Amphetamine abuse may play a role in acute myocardial infarction. Adverse
cardiovascular manifestations of amphetamine can occur with sudden overt chest
pain or present insidiously. In view of the potential association of amphetamine
and myocardial infarction, physicians should not rely only upon clinical
symptoms. This report highlights the diabetic patients with amphetamine abuse
should undergo a routine electrocardiogram in such circumstances.
PMID- 24353689
TI - Diabetic foot ulcers combination with lower limb lymphedema treated by staged
charles procedure: case report and literature review.
AB - Primary or secondary, lymphedema is lymphatic dysfunction which results in
protein-rich interstitial fluid accumulated in the skin and subcutaneous tissue.
In developed countries, surgical resection of regional lymph nodes or chronic
inflammation process is the most common etiology of lymphedema instead of
parasite infection seen in developing countries. Patients with lymphedema sustain
either cosmetic or functional problems, and several studies have indicated the
potential risk, though not high, transforming lymphedema to lymphangiosarcoma.
Here we introduce a simple idea with staged Charles procedure by a case report to
decrease the size of wound healing in each procedure and decreasing the rate of
surgical complication.
PMID- 24353690
TI - Orbital Rosai-Dorfman Disease in a fifty-eight years old woman.
AB - Rosai-Dorfman disease (RDD) is rare and characterized by histiocytic
proliferation and massive cervical lymphadenopathy. About 40% of patients have
extra-nodal involvement. Opthalmic involvement is seen in 10% of cases. A case of
orbital Rosai Dorfman disease in a 58 years old woman is presented here, who was
misdiagnosed as orbital inflammatory disease initially. The patient did not
respond to a course of oral prednisolone. Then complete surgical excision of the
mass was performed and the histopathological examination was consistent with a
diagnosis of RDD.
PMID- 24353691
TI - Post-hysterectomy vaginal cuff cancer secondary to HPV infection and CIN: A case
report.
AB - We present a case report of secondary vaginal cancer after complete hysterectomy
due to myoma that was complicated by low-grade cervical intraepithelial neoplasia
(CIN I) and human papilloma virus (HPV) infection. After complete hysterectomy,
the HPV DNA level in the vaginal tissue was obviously increased, and vaginal
cancer was diagnosed 6 months later. We conclude that HPV infection can cause
vaginal cancer after complete hysterectomy in cases complicated by CIN.
Therefore, HPV should be regularly assessed during the postoperative follow-up
period.
PMID- 24353692
TI - Basic steps in establishing effective small group teaching sessions in medical
schools.
AB - Small-group teaching and learning has achieved an admirable position in medical
education and has become more popular as a means of encouraging the students in
their studies and enhance the process of deep learning. The main characteristics
of small group teaching are active involvement of the learners in entire learning
cycle and well defined task orientation with achievable specific aims and
objectives in a given time period. The essential components in the development of
an ideal small group teaching and learning sessions are preliminary
considerations at departmental and institutional level including educational
strategies, group composition, physical environment, existing resources,
diagnosis of the needs, formulation of the objectives and suitable teaching
outline. Small group teaching increases the student interest, teamwork ability,
retention of knowledge and skills, enhance transfer of concepts to innovative
issues, and improve the self-directed learning. It develops self-motivation,
investigating the issues, allows the student to test their thinking and higher
order activities. It also facilitates an adult style of learning, acceptance of
personal responsibility for own progress. Moreover, it enhances student-faculty
and peer-peer interaction, improves communication skills and provides opportunity
to share the responsibility and clarify the points of bafflement.
PMID- 24353693
TI - Effect of anthropometrical measurements on portal vein and hepatosplenic span.
PMID- 24353694
TI - Proceedings of Endocrine Surgical Course held at JPMC Karachi Pakistan from June
17-19(th) 2013.
PMID- 24353695
TI - Using Tacrolimus in Living Donor Liver Transplantation Recipients with High Model
for End-stage Liver Disease Scores Might Increase the Risk of Postoperative
Neuropsychologic Deficits.
PMID- 24353696
TI - Are the Editors faced with e-problems performing their duties and
responsibilities satisfactorily?
AB - Astonishing revolution in information technology, developments in electronic
publishing and availability of manuscript management software's has provided lot
of facilities to authors, reviewers as well as editors but it has also given
birth to lot of e-problems. This communication highlights some of these e
problems besides discussing the manuscript management system practiced by
Pakistan Journal of Medical Sciences through modified Open Journal System. It
also cautions the editors of small journals faced with financial and human
resource constraints to keep themselves abreast of all these developments, go for
automation in e publishing gradually as all the stake holders i.e. authors,
reviewers and office management staff learns these and become used to it.
PMID- 24353697
TI - DORA Declaration: Delayed Diagnosis of Debilitating Dilemma.
PMID- 24353698
TI - The touch of madness:manto as a psychiatric case study.
AB - Saadat Hasan 'Manto' is widely acknowledged as one of the greatest short story
writers in the world. He died at the age of forty three from complications of
alcoholism. All of his life, he suffered from symptoms of anxiety and depression
and his alcohol abuse was intimately linked both to his mental distress as well
as his creative genius. This paper examines the life of Manto from a psychiatric
perspective and the link between creativity and mental illness. We show how
Manto's particular family circumstances led to the development of restlessness
and later anxiety in his life; how his substance abuse, especially alcohol abuse
exacerbated this mental distress and how it eventually led to his death and how
all of these factors were intimately linked to his creative genius and were the
source of so many of his literary masterpieces. METHODS: We reviewed seventy five
short stories considered to be his best. Writings about Manto's life including
his own were reviewed to construct a picture of his life as well as find clues to
his mental distress and alcohol abuse. A literature search for articles related
to creativity and mental illness was conducted using Google Scholar containing
the search terms 'creativity and madness' and 'creativity and mental illness' in
the titles of the articles. References most relevant to our case study were
identified. CONCLUSION: Manto suffered from symptoms of anxiety and depression
which today would meet the diagnostic criteria for Alcohol Dependence and, in
later life, Alcohol-induced Psychosis. Appropriate treatment may have prolonged
his life although that may have come at the expense of his creativity.
PMID- 24353699
TI - Risk factors and mortality among newborns with persistent pulmonary hypertension.
AB - OBJECTIVE: To determine the risk factors for persistent pulmonary hypertension of
newborns (PPHN) and their influence on mortality. METHODS: This was an
observational study conducted at The Children's Hospital & the Institute of Child
Health, Multan, Pakistan, from July 2011 to June 2012.All admitted babies who had
respiratory distress, cyanosis and evidence of hypoxia on ABG,s were diagnosed
provided that they were having right- to- left or bidirectional hemodynamic
shunting at the ductus arteriosus or at patent foramen ovale along with Tricuspid
regurgitation (TR) jet >40 mm of Hg on echocardiography. All the demographic,
maternal, antenatal, natal and postnatal data were recorded on a predesigned
Performa. RESULTS: There were 79 patients, including 61 males and 18 females. The
most common risk factors observed in our study were male sex (72.1%), cesarean
section mode of delivery (54.2%), positive pressure ventilation while
resuscitation (44.2%) birth asphyxia (40.4%) and meconium aspiration syndrome
(MAS)35.4%. It was found that male sex (88.8%), cesarean-section delivery
(77.7%), respiratory distress syndrome (RDS) 44.8% and sepsis (44.4%) were more
associated with PPHN in premature infants than with term and post term infants.
Out of the total 79 patients, death occurred among 7 preterm and 14 terms and
post term infants. As a whole, cesarean section mode of delivery (71.4%), birth
asphyxia (57.1%) and female sex (52.4%) were found major risk factors associated
with mortality. However, respiratory distress syndrome (Relative Risk RR=5),
birth asphyxia (RR=2.5) and male sex (RR=2)were found to be associated with
increased risk of mortality in preterm than term and post term infants.
CONCLUSION: Male gender, cesarean section mode of delivery, MAS and RDS are the
major risk factors for PPHN in any age group. RDS, Birth asphyxia and male sex
are associated with increased risk of mortality in pre term than term and post
term infants.
PMID- 24353700
TI - Risk factors for acquisition of ventilator-associated pneumonia in adult
intensive care units.
AB - OBJECTIVE: Ventilator Associated Pneumonia (VAP) has an imperative place amongst
nosocomial infections leading to increase morbidity and mortality rates. The
present study aimed to determine risk factors for acquisition of ventilator-
associated pneumonia in an intensive care unit (ICU). METHODS: A nested case
control study was carried out from September 2007 to June 2008. All 183 patients
hospitalized at the adult ICU ward in Be'sat Hospital, Sanandaj city western Iran
over a 48 hour period were included. Bacteriologic diagnosis and antibiotic
susceptibility patterns were performed based on Edward & Ewing's methods and CLSI
system guidelines. Results : Of the 149 samples which were taken from
endotracheal tubes of 183 patients, 48 cases were diagnosed for VAP with an
incidence rate of 26.2%. Mean duration of hospitalization was 23.4+/-10.2 days.
The maximum and minimum antibiotic resistance for the gram negative bacteria was
93.3% for Cefalotin and 50% for Amikacin. The main risk factors for acquisition
of ventilator- associated pneumonia were mechanical ventilation (Adjusted OR:
1.55, 95% CI: 1.37-1.74), history of antibiotic consumption (AOR: 8.92, CI: 1.16-
66.66) and fever (AOR: 3.11, CI: 1.22- 7.93). CONCLUSIONS: VAP is significantly
related to ICU hospitalization, mechanical ventilation and history of antibiotics
consumption. Cefalotin and Amikacin showed the highest and lowest antibiotic
resistance against gram negative bacteria respectively.
PMID- 24353701
TI - The common causes leading to pancytopenia in patients presenting to tertiary care
hospital.
AB - OBJECTIVE: The objective of this study was to determine the frequency of common
causes leading to Pancytopenia in patients presenting to tertiary care hospital
at Karachi. METHODS: A total of 62 patients with the diagnosis of Pancytopenia of
more than one week duration were enrolled in the study. All patients underwent a
detailed medical history and full physical examination followed by blood sampling
for the investigations i.e. complete blood count with peripheral film,
erythrocyte sedimentation rate (ESR), Malarial parasites (MP), liver function
test, Renal function tests, PT and viral profile (HBsAg, Anti-HCV),
Ultrasonography of abdomen. All patients underwent bone marrow aspiration and
trephine biopsy for reporting and interpretation. Duration of study was six
months, from May 2010 to November 2010. RESULTS: The average age of the patients
was 37.76 +/- 16.38years. Out of 62 patients, 36 (58%) were male and 26 (42%)
were female. Megaloblastic anemia was the commonest cause that was observed in
41.9% cases followed by acute myeloid leukemia 27.4%, aplastic anemia 19.4% and
erythroid hyperplasia 11.3%. Conclusion : This study concluded that most common
cause of pancytopenia is Megaloblastic anemia, followed by acute myeloid leukemia
and aplastic anemia. Bone marrow examination is a single useful investigation
which reveals the underlying cause in patients with pancytopenia.
PMID- 24353702
TI - Investigation of the oral infections and manifestations seen in patients with
advanced cancer.
AB - OBJECTIVE: A prospective, observational study was undertaken to investigate the
epidemiology of oral infection among the patients with advanced malignancies, and
to investigate the effects of therapy strategies and risk factors on the
incidence of oral infection. METHODS: The patients with advanced malignancies
were enrolled into the study. The incidence of oral infection with different
malignant tumor groups or different treatment methods and the diagnoses of oral
infection were confirmed. Demographic data on age, gender, bed rest time,
nutritional status, smoking habit and the presence of oral prosthesis were also
recorded. RESULTS: Oral infection was prevalent in 46% (391/850) of all cancer
patients, with the highest rate in oral and maxillofacial cancer group (67%),
followed by Hematological malignancy group (58.6%) and other groups (ranging from
43.3% to 35.3%). Oral candidiasis, oral herpes simplex, and oral mucositis were
the popular infectious diseases in the patients. Chemotherapy and radiotherapy,
especially combined radio- and chemotherapy, resulted in more oral infections
compared with palliative care and surgery. Poor nutritional status and oral
prosthesis were identified as independent risk factors associated with oral
infection. CONCLUSION: Oral infection is prevalent among advanced cancer patients
and associated with therapy methods and risk factors. More oral health care
should be carried out for the patients with advanced malignant tumor.
PMID- 24353703
TI - Factors associated with epileptic seizure of cavernous malformations in the
central nervous system in West China.
AB - OBJECTIVE: To explore the factors associated with preoperative and postoperative
epileptic seizure in patients with cavernous malformations (CMs). METHODS: A
total of 52 consecutive patients from January 2009 to June 2011 who underwent
surgical treatment in West China Hospital of Sichuan University due to CMs and
confirmed by histopathology were retrospectively reviewed.Patients were divided
into two groups (epilepsy-group and non-epilepsy group) according to clinical
presentation. Other clinical data, treatment procedure, and follow-up information
were collected. Engel classification was used to evaluate seizure outcome.
RESULTS: Low birth weight, temporal lobe involvement and cortical lesion showed
significant difference between two groups (p=0.017, 0.003 and 0.025
respectively). Cortical lesion highly increased risk for preoperative epileptic
seizure (OR=10.48; 95% CI 1.61-68.23). After a mean follow-up of 2.1 years, 77.8%
of epileptic patients achieved Engel class I. Temporal lobe involvement, lesion
size < 2.5cm and surgery within one year of symptom onset were found associated
with better seizure outcome (p=0.016, 0.012 and 0.050). Temporal lobe involvement
significantly decreased the risk for postoperative epileptic seizure (OR=0.038;
95% CI 0.002-0.833). Application of ECoG made no significant difference to
seizure outcome (p=0.430). Most patients need continuing medication therapy after
surgery. CONCLUSION: Surgical treatment of patient with CMs is satisfactory in
most cases and temporal lobe involvement usually predict favourable postoperative
seizure outcome whether under the monitoring of ECoG or not. Thus, epileptic
patients with CMs should be considered for surgical treatment especially when
cortical brain layer or temporal lobe was involved.
PMID- 24353704
TI - Effect of psychoeducation and telepsychiatric follow up given to the caregiver of
the schizophrenic patient on family burden, depression and expression of emotion.
AB - OBJECTIVE: This randomized-controlled experimental study was conducted to
determine the effects of psychoeducation in the inpatient clinic and regular
telepsychiatric follow-up (via telephone) after discharge on emotional
expression, depression and family burden of primary caregivers of the
schizophrenic patients. METHODS: This study was performed on 62 caregivers of the
schizophrenic patients, assigned to experiment (n=32) and control (n=30) groups,
from 1(st) July 2010 to 31(st) May 2011. The Scales for Expressed Emotion, the
Beck Depression and the Zarit Family Burden were applied for the caregivers in
experiment and control groups before education, after education and after 6
months telephone follow-up. RESULTS: The mean scores of the caregivers in
experiment group on family burden, emotional expression and depression were
decreased after education and after telephone follow-up and difference was
significant (p<0.001). Conclusions : Psychoeducation and telepsychiatric follow
up via telephone induced decrease in family burden, emotional expression and
depressive symptoms for their caregivers and was a support for the family in the
patient care.
PMID- 24353705
TI - Neonatal seizures, experience at Children Hospital and Institute of Child Health
Multan.
AB - OBJECTIVE: The study was conducted to determine the etiology of seizures in
neonates. METHODS: This was a descriptive Cross-sectional study. This study was
conducted at neonatal unit of children hospital and institute of child health
Multan from June 2012 to April 2013. A total of 285 neonates who presented with
seizures were enrolled for the possible causes. First line investigations
including blood glucose, serum calcium, serum magnesium, serum sodium, complete
blood counts, serum creatinine, liver function tests, ABGs, cerebrospinal fluid
examination, cranial ultrasound and EEG were done in all neonates. Second line
investigations (blood culture, CT scan, MRI, screening for inborn error of
metabolism and Torch antibody titer) were done in selected neonates. The data was
analyzed using SPSS-10. RESULTS: Out of 285 neonates, 175(61.4%) were male and
110(38.6%) female. There were 199(69.8%) term and 86 (30.2%) preterm. Birth
asphyxia was the commonest cause of seizures and present in 53.7% neonates and
metabolic disturbance in 17.5%. Seizures with unknown etiology were present in
5.3% neonates. CONCLUSION: In most of the cases, the causes of neonatal seizures
were present. Birth asphyxia was the main etiology identified. However, to
establish the exact cause of seizures, more extensive work up is needed.
PMID- 24353706
TI - Pattern of QTc prolongation in Methadone Maintenance Therapy (MMT) subjects
receiving different methadone dosages: A prospective cohort study.
AB - OBJECTIVES: This study aimed to compare the QTc interval between low and high
dose methadone groups and evaluate the pattern of QTc variation. METHODS: This is
a prospective cohort study conducted from December 2010 till August 2011 at
Malaysian University of Science's Hospital. Forty six subjects, grouped in high
dose (>80mg) and low dose (<80mg) oral methadone, were followed-up at 4-weekly
for QTc measurements. Relevant demographic and biochemical profiles were taken at
intervals with concurrent QTc measurements. RESULTS: No significant QTc
differences between methadone dosage groups were found at Week 0 (434ms vs 444ms,
p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs
450ms, p = 0.029). However, there were significant associations between the
groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044
and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR
2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the
sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and
0.017, respectively), but not at week 8. CONCLUSION: High-dose methadone group is
more likely to develop prolonged QTc than low-dose group. However, such effects
were inconsistent and occurred even during chronic methadone therapy, mandating
judicious QTc and serum methadone monitoring.
PMID- 24353707
TI - Relationship of serum uric Acid level and angiographic severity of coronary
artery disease in male patients with acute coronary syndrome.
AB - BACKGROUND AND OBJECTIVE: The association between serum uric acid and ischemic
heart disease remains controversial and it has not yet been established as
cardiovascular risk factor. Our objective was to study the association of serum
uric acid level with angiographic severity of coronary artery disease in men with
acute coronary syndrome (ACS). Methods : This cross-sectional study was conducted
on 100 consecutive male patients presenting with ACS at Punjab Institute of
Cardiology. Hyperuricemia was defined as serum uric acid level > 6.5 mg/dl.
Severity of ischemic heart disease was assessed on the basis of Gensini score,
number of diseased vessels, critical lesions and total occlusions on coronary
angiogram. RESULTS: Mean age of normouricemic group (n=59) was 52.62 +/- 9.46
years and mean age of hyperuricemic group (n=41) was 50.52 +/- 9.40 years
(p=0.273). Mean uric acid level; normouricemic group (4.75 +/- 1.05),
hyperuricemic group (7.61 +/- 1.24), p<0.001. Mean Gensini score; normouricemic
group (22.15 +/- 21.52), hyperuricemic group (35.69 +/- 26.80). Mann Whitney U
test was applied to compare the Gensini score of two groups and it showed
statistically significant difference (p value <0.006). Critical lesions, total
occlusions and multi-vessel disease were more frequent in hyperuricemic group but
statistically significant difference was found only for total occlusions
(p=0.013) and critical lesions (p=0.046). Conclusions : Hyeruricemia is
associated with higher Gensini score and more frequent total occlusions and
critical lesions in men presenting with acute coronary syndrome.
PMID- 24353708
TI - Hepatitis C genotype and associated risks factors of patients at University
Kebangsaan Malaysia Medical Centre.
AB - OBJECTIVES: Hepatitis C virus (HCV) genotyping is important for treatment and
epidemiological purposes. The objective was to determine HCV genotype and their
associations with certain risk factors at University Kebangsaan Malaysia Medical
Centre (UKMMC). METHODS: A total of 89 samples were collected from December 2009
to January 2011. Demographic data of patients were collected from medical record.
Reverse Transcriptase Polymerase chain reaction (RT PCR) was performed and sixty
four samples yielded positive for HCV. Sequencing was performed and analyzed
based on sequence information in GenBank. Statistical analysis were done using
SPSS version 15. Results : HCV genotype 3 (73%) was the most frequent genotype,
followed by genotype 1(27%). The distribution of HCV genotype/ subtype was as
follows: 3a (64.8%), 1a (13.5%), 1 (10.8%), 3 (8.1%) and 1b (2.7%). CONCLUSIONS:
HCV subtypes 3a, 1a, and 1b were identified in patients at UKMMC, Malaysia with
subtype 3a being the most prevalent. No significant association was found between
HCV genotypes and patients' demographic data.
PMID- 24353709
TI - Diabetes education improves depressive state in newly diagnosed patients with
type 2 diabetes.
AB - OBJECTIVES: The prevalence of depression is relatively high in individuals with
diabetes. However, screening and monitoring of depressive state in patients with
diabetes is still neglected in developing countries and the treatment of diabetes
related depression is rarely performed in these countries. In this study, our aim
was to study the role of diabetes education in the improvement of depressive
state in newly diagnosed patients with type 2 diabetes. METHODS: The Dutch
version of the center for epidemiological studies depression scale (CES-D scale)
and the problem areas in diabetes (PAID) questionnaire were used to assess
depression and diabetes-specific emotional distress in 1200 newly diagnosed male
adult patients with type 2 diabetes before and after a two-week diabetes
education by professionally trained nurses. Pearson correlation and regression
analysis were used to analyze the factors related to depression in patients with
type 2 diabetes. RESULTS: The incidence of depression in newly diagnosed patients
with type 2 diabetes was 28%, and the rate of diabetes-specific emotional
distress was 65.5%. High education levels, low income were correlated to
depression in individuals with diabetes. After two weeks of diabetes education,
the incidence of depression and diabetes-specific emotional distress decreased
significantly to 20.5% (P < 0.05) and 11% (P < 0.001), respectively. CONCLUSIONS:
The incidence of depression, especially diabetes-specific emotional distress, was
relatively high in newly diagnosed patients with type 2 diabetes. The depression
state could be improved by diabetes education.
PMID- 24353710
TI - Pancytopenia in children: A 6-year spectrum of patients admitted to Pediatric
Department of Rehman Medical Institute, Peshawar.
AB - OBJECTIVE: To determine the various spectrum of pancytopenia with its frequency
on the basis of bone marrow examination in children from 6 months to 14 years.
METHODS: A retrospective descriptive study was carried out at Department of
Pediatric Rehman Medical Institute Peshawar from January 2006 to December 2012. A
total of 205 patient's age between 6 months and 14 years, fulfilling the
inclusion and exclusion criteria were included in the study. Complete blood
count, peripheral smear, bone marrow examination and Serum vitamin B12 level was
done in all the cases. RESULTS: Out of 14642 patients admitted to the Pediatric
department during the study period, 205 (1.4%) patients were pancytopenic on
their peripheral blood smear. Male outnumbered female with a ratio of 1.8:1.
42.5% of the patients were in the age group of 1 month to 5 years. Common
etiological pattern identified were Aplastic anemia 58(28.3%), Hematological
malignancies 49 (23.9%), megaloblastic anemia 40 (19.5%), idiopathic
thrombocytopenic purpura 16 (7.8%), iron deficiency anemia 9 (4.4%), hemolytic
anemia 7 (3.41%), Visceral leishmaniasis 6 (2.93%), hypersplenism 5 (2.44%),
malaria 5 (2.44%), anemia of chronic disorder 4 (1.95%), Myelodisplastic syndrome
3 (1.46%), Niemen pick disease 2 (0.97%) and Gaucher disease in 1(0.49%). Common
clinical presentations were fever, pallor, body aches, petechial hemorrhages and
epistaxis. CONCLUSION: Pancytopenia is one of the importance occurrences in
pediatric patients. Acute leukemia and bone marrow failure are the most common
causes yet megaloblastic anemia and infections are the treatable and reversible
causes of pancytopenia.
PMID- 24353711
TI - Expression levels of ERCC1 and RRM1 mRNA and clinical outcome of advanced non
small cell lung cancer.
AB - OBJECTIVE: We conducted a study to understand the genetic effect of ERCC1 and
RRM1 on the chemotherapy response and clinical outcome of Non-Small Cell Lung
Cancer (NSCLC). METHODS: The relative cDNA quantification for ERCC1 and RRM1 was
conducted using a fluorescence-based real-time detection method among 294 NSCLC
patients. RESULTS: Compared with the internal reference gene beta-action, the
median levels of ERCC1 and RRM1 expression were 2.43*10(-2) and 0.11*10(-2),
respectively. Our study showed response to platinum-containing regimen
chemotherapy was high in those with high ERCC1 expression, and the OR (95% CI)
were 1.73(1.06-2.81). An apparently high response to chemotherapy was decreased
when patients were carrying both high expression of ERCC1 and RRM1, with OR (95%
CI) of 2.57(1.21-4.90). Patients with high expression of ERCC1 were associated
with a longer OS by multivariate Cox proportional hazards model. Moreover, those
carrying both high levels of ERCC1 and RRM1 were seem to have a longer OS when
compared with those with low expression (HR=0.31, 95% CI=0.13-0.62 for OS).
CONCLUSION: This observation could be used in personalized chemotherapy, increase
the response rate and prolonged survival time, and could encourage to explore the
predictive value of other genes.
PMID- 24353712
TI - Identification of etiological agents by LPA and PCR in childhood meningitis.
AB - OBJECTIVES: To determine the etiological agents by Latex Particle Agglutination
(LPA) and Polymerase Chain Reaction (PCR) in patients admitted with Cerebrospinal
Fluid (CSF) culture negative bacterial meningitis Methods: This descriptive case
series was conducted at National Institute of Child Health, Karachi from January
2010 to December 2012. Patients meeting the WHO case definition of suspected
meningitis from one month to 59 months of age were included in the study. CSF
examination and culture was carried out on every patient and CSF culture negative
patients were enrolled. Demographic data, clinical signs & symptoms and
laboratory findings were entered into the proforma. Data was analyzed using
statistical package for social sciences (SPSS) version 17. P-value <0.05 was
taken as significant. RESULTS: A total of 166 patients were included. Male were
96 and female were 76 with the male to female ratio of 1.26. The mean age of
patient was +/- SD 14.6 +/- 14.5 months. The etiological agents identified by LPA
were in 26/166 (15.66%) cases and the organisms were H. influenzae type b 10
cases, streptococcus pneumoniae 15 cases and meningococcus only one case
respectively. The organisms identified by PCR were in 65/166 (39.15%) cases and
the isolates were H. influenzae type b 16 cases, streptococcus pneumoniae 48
cases and meningococcus 01 case respectively. CONCLUSION: LPA and PCR are
superior and useful diagnostic tools in microbiology. They can be used for rapid
etiological diagnosis of bacterial meningitis for the early administration of
proper antibiotic. Abbreviation: LPA = Latex Particle Agglutination, PCR =
Polymerase Chain Reaction, CSF = Cerebrospinal Fluid, CNS = Central Nervous
System.
PMID- 24353713
TI - Role of rapid diagnostic tests for guiding outpatient treatment of febrile
illness in Liaquat University Hospital.
AB - OBJECTIVES: To assess the validity /strength of clinical diagnosis of Malaria on
the basis of IMNCI algorithm by slide microscopy (gold standard) and to compare
the effectiveness of Rapid Diagnostic Test (RDT )against slide microscopy.
Methods : It is a descriptive cross sectional study of 6 month duration conducted
at Pediatric Outpatient Department LUH Hyderabad from June-Dec. 2010. Sample of
400{the minimum required sample was 385 with malaria prevalence 5% (0.05) with
margin of error of 3% (0.03, frequency vary from 2-8 % among different studies)}
febrile children under 5 years classified as Suspected Clinical Malaria according
to algorithm of IMNCI were included; The operational definition for Suspected
Clinical Malaria was; fever for more than 2 days with no runny nose, no measel
rash and no other cause of fever. Hyderabad was considered as low risk area.
Rapid diagnostic test (RDT) and slide microscopy were done, and only confirmed
cases were treated according to current guidelines given by National Malaria
Program/updated IMNCI. RESULTS: Total 2000 patients under 5 years presented with
fever and were evaluated. From 2000 cases 20% (400) were diagnosed as suspected
clinical Malaria according to IMNCI algorithm; and only 40 cases (10%) have shown
positive results for malaria parasite on slide microscopy and 38 cases on RDT.
Regarding the plasmodium species 70% were vivax and 30% were falciparum. As
regards the effectiveness, RDT has shown 95% sensitivity for the detection of
plasmodium antigens in the febrile clinically suspected cases of malaria.
CONCLUSION: Prompt and accurate diagnosis of malaria is needed for implementation
of appropriate treatment to reduce unnecessary anti-malarial prescription. RDT is
as effective as slide microscopy for the diagnosis of malaria especially in
resource poor countries.
PMID- 24353714
TI - Human papillomavirus infection a favorable prognostic factor in laryngeal
squamous cell carcinoma is associated with the expression of proliferating cell
nuclear antigen.
AB - OBJECTIVE: It has been documented that human papilloma virus (HPV) DNA
replication requires proliferating cell nuclear antigen (PCNA). However the
association between them in tumors is still controversial. Up to now, the role of
HPV in laryngeal squamous cell carcinoma (LSCC) has not been clearly established,
and the correlation between HPV and PCNA in LSCC remains poorly explored.
METHODS: We retrospectively reviewed the clinicopathological features and follow
up data of 71 patients with LSCC. The lesions were examined for PCNA using
immunohistochemistry, and for HPV using in situ hybridization. RESULTS: 31
(43.7%) cases showed infection of HPV and 38 (53.5%) showed overexpression of
PCNA. No significant difference of HPV status in clinicopathological features was
found. While there was a significant difference of PCNA expression in histology
grade but no significant difference of PCNA expression in other
clinicopathological features could be detected, and the expression of PCNA is not
a significant predictor of survival in LSCC patients. However, HPV infection is a
favorable prognostic factor in LSCC patients. Moreover, HPV infection is
associated with PCNA overexpression. CONCLUSION: Human papilloma virus (HPV)
infection is an indicator of better prognosis in LSCC and associated with the
expression of PCNA.
PMID- 24353715
TI - The incidence, pattern and outcome of stray bullet injuries. A growing challenge
for surgeons.
AB - OBJECTIVE: To study the incidence, pattern of injuries, presentation and
management of stray bullet injuries. METHODS: All patients presented and admitted
with stray bullet injuries during a period of 4 years from January 2006 to
December 2010 were included in this prospective study which was conducted at
Liaquat University of Medical and Health Sciences Hospital Hyderabad/Jamshoro.
All of the study subjects were admitted through casualty and were initially
thoroughly examined and resuscitated. The pattern of injuries was noted and
requisite investigations performed. Patients who sustained injuries demanding
surgery were prepared accordingly and were submitted for laparotomy or other
procedures depending upon the severity of injuries. The data collected on
individual basis and variables studied including demographics, pattern of
injuries, time since injury occurred and management. RESULTS: A total number of
165 patients with a mean age of 17.1 years, SD 13.807 and range of 74(2-76)
presented with stray bullet injuries during study period. The study population
comprised 117(70.90%) males and 48(29.09%) females. Majority of the patients were
brought late because of delay in diagnosis or delay in transportation. The
commonest victims were young children in their teens and comprised 78% of the
study population. Haemothorax/ pneumothorax or peritonitis was the common
presentations occurring in 11% and 61.81% of the study population respectively.
Of the total number, 92 (55.75%) patients underwent laparotomy while remaining
patients either had chest intubation or some other procedures done accordingly.
Nine (5.45%) patients developed permanent disabilities while 13(7.87%) patients
died either immediately after arrival or later on in the hospital during or after
the operative treatment. Mortality was related to the time of arrival in hospital
since the injury and thus was highest among those brought 4 or more hours after
the shot (P<0.001). Patients who did not sustain major injuries were kept under
observation and were subsequently discharged. CONCLUSION: Stray bullet injuries
are an ever increasing challenge in our society. Unlawful and jubilant use of
weapons in celebrations, weddings and similar occasions are causing a lot of
morbidity and mortality in the society.
PMID- 24353716
TI - Predictive role of Glutathione S-transferases (GSTs) on the prognosis of
osteosarcoma patients treated with chemotherapy.
AB - OBJECTIVE: We conducted a comprehensive study to investigate the role of GSTM1,
GSTTI and GSTP1 genetic variation involved in transport pathways in response to
chemotherapy and clinical outcome of osteosarcoma. METHODS: A total of 146
patients were included in our study between January 2008 and December 2009. All
the patients were followed up to death or January 2012. Genotyping of GSTM1,
GSTT1 and GSTP1 was conducted in a 384-well plate format on the Sequenom
MassARRAY platform. RESULTS: Sixty seven patients (45.9%) died during the follow
up period. The median age of patients was 14.2 years and ranged from 9.3 to 38.7
years. The median follow-up time was 29.6 months (range 5 to 60 months).
Individuals with GSTP1 G/G genotype tended to live shorter than A/A genotype, and
we found a significantly higher risk of death from osteosarcoma (adjusted
HR=2.73, 95% CI=1.05-7.45). Individuals with the GSTP GG genotype were more
likely to have a poor response to chemotherapy, with an OR of 2.73 (95%CI, 1.07
7.81). However, we did not find association of polymorphisms in GSTM1 and GSTT1
with response to chemotherapy and prognosis of osteosarcoma. CONCLUSION: Our
study provides information for prediction of treatment outcome in clinical
oncology. Due to the limited number of samples, the results of our study need to
be confirmed by large sample size studies.
PMID- 24353717
TI - Thyroid diseases in pregnancy: The importance of anamnesis.
AB - OBJECTIVE: Primary objective of our study was to evaluate the efficiency of
detailed medical history and thyroid examination of the pregnant women presenting
to our clinic from Rize province and nearby which was an endemic goiter region.
It was aimed to investigate the frequency of thyroid diseases, pregnancy outcomes
and the efficiency of screening with thyroid function tests during the first
trimester of pregnancy as secondary endpoint. Methodology : A prospective
clinical study was conducted with 998 pregnant women between the ages of 17-48
years. In the first step of our study, a detailed medical history was obtained
and a detailed thyroid gland examination was performed in all the patients
(n=998). In the patients diagnosed with thyroid disease or considered to have
thyroid disease with these results (n=107), thyroid diseases were evaluated with
thyroid function tests and imagining methods. Analyses of socio-demographic data
and nutrition were also made. In the second step, thyroid stimulating hormone
(TSH), free T3 and free T4 tests were performed in the first antenatal
examination of the pregnant cases considered not to have thyroid disease after
medical history and examination (n=891). Parameters of thyroid peroxidase
antibodies (TPOAb), thyroglobulin antibodies (TgAb) and TSH receptor auto
antibodies (TRAb) were investigated in the cases whose TSH, sT3 and sT4 levels
were different than the reference values after examination of the
endocrinologist. Thyroid ultrasonography was performed. Urinary iodine levels in
24 hour urine were investigated. RESULTS: During pregnancy, the incidence of
hyperthyroidism and hypothyroidism in the whole study group were 2.8% (28/998)
and 4.3% (43/998), respectively, 6.7% of the patients (67/998) had a diagnosis of
thyroid disease before pregnancy. Hyperthyroidism and hypothyroidism depending on
the TSH screening results were 1.9% (17/891) and 1.1% (10/891) respectively and
the incidence of overt hyperthyroidism and overt hypothyroidism were 0.2% (2/891)
and 0.2% (2/891) in the pregnant cases considered not to have thyroid disease
with medical history and examination. CONCLUSION: Detailed medical history and
family history obtained during the first trimester of pregnancy helped us to
identify 6.7% of thyroid diseases among the pregnant women. This result
effectively emphasizes the importance of detailed first prenatal examination
regarding the thyroid.
PMID- 24353718
TI - Changes of quality of life after gastric tube reconstruction in adenocarcinoma of
the esophagogastric junction.
AB - OBJECTIVE: To investigate changes of quality of life (QOL) of patients with
adenocarcinoma of the esophagogastric junction (AEG) after gastric tube
anastomosis. METHODS: From January 2009 to December 2011, eighty-seven patients
with Types II and III AEG were selected for gastric tube reconstruction after
proximal gastrectomy. The QOL of the patients was assessed using the Chinese
versions of the EORTC QLQ-C30 and the EORTC QLQ-STO22 preoperatively, as well as
one and two years postoperatively. RESULTS: The QLQ-C30 showed that the global
health of the respondents decreased at one year after the surgery (P=0.02). The
preoperative score for physical function was significantly better than the one-
and two-year post-operation scores. The preoperative scores for pain, nausea and
vomiting, and economic difficulties were worse than the one- and two-year post
operation scores (P<0.05). Diarrhea was worse at one year post-operation than
during pre-operation (P = 0.00), but improved at two years after the operation.
The QLQ-STO22 scales showed that the preoperative dysphagia score was better than
one-year post-operation, and no significant differences were observed in terms of
dysphagia between the pre-operation and two-year postoperative periods.
Preoperative reflux and taste scores were better than those after the operation
(P<0.05). The hair loss score at one-year post-operation was worse than at either
pre-operation or two-year post-operation. CONCLUSIONS: Most QOL scales worsened
after surgery, particularly at postoperative year one. However, the scales can be
gradually recovered to preoperative levels. The physical function, nausea and
vomiting, reflux, taste, and financial difficulties did not fully recover two
years after the operation.
PMID- 24353719
TI - Prophylactic antibiotics used in patients of hepatobiliary surgery.
AB - OBJECTIVE: To clarify the use of antibiotics in our hospital and to guide the
prophylactic use in future hepatobiliary surgical procedures. METHODOLOGY: A
retrospective review of patients who underwent hepatobiliary surgery from January
2011 to June 2011 was included. Data were collected, and surgical site infection
(SSI) was defined by the criteria of Center for Disease Control and Prevention.
Patients were prescribed antibiotics for the clinical diagnosis of hepatobiliary
system diseases. RESULTS: 1564 patients were identified, in which 784 patients
(50.13%) did not receive preoperative antibiotic prophylaxis. Of these 355
patients with 784 surgical sites received either preoperative or both
preoperative and postoperative antibiotic prophylaxis. The SSI rate of the
patients who received prophylaxis alone (2.56%, 20 of 780 sites) was not
statistically higher than that of the patients who have not received prophylaxis
(2.68%, 21 of 784 sites), and the two groups were not statistically correlated
(P=0.77). CONCLUSION: The number of the patients who developed SSI was relatively
low, and no reduction in the SSI rate was observed among the patients who have
received antibiotic prophylaxis.
PMID- 24353720
TI - Prevalence of blindness and causes of visual impairment among adults aged 50
years or above in southern. Jiangsu Province of China.
AB - OBJECTIVE: The prevalence of blindness and low vision among adults aged >=50
years in southern Jiangsu Province were surveyed and estimated. METHODS: Cluster
sampling was employed from January to September 2010 to randomly select 6,722
individuals aged >=50 years in 28 clusters from southern Jiangsu Province. The
survey was preceded by a pilot study, which refined operational methods and
conducted quality assurance evaluation. Eligible individuals were registered for
visual acuity measurement and eye examination. RESULTS: A total of 6,155
individuals were recruited, and a response rate of 91.50% was obtained. The
prevalence of bilateral blindness and low vision were found to be 0.76% and
1.37%, respectively. Subjects with monocular blindness and low vision were 3.27%
and 3.48%, respectively. Among the individuals evaluated, 201 were detected to
have monocular blindness and 47 with bilateral blindness. In addition, 55 of the
201 subjects with monocular blindness were found to suffer from low vision of the
other eye. Among the 295 subjects with blind eyes, 116 (39.32%), 31 (10.51%), and
28 (9.49%) were caused by cataract, high myopia macular degeneration, and
atrophic eyeballs, respectively. In the 437 subjects with low-vision eyes, 223
(51.03%), 41 (9.38%), and 41 (9.38%) had cataract, high myopia macular
degeneration, and age-related macular degeneration, respectively. CONCLUSIONS:
Blindness and low vision are caused by descending cataract, age-related macular
degeneration, high myopia macular degeneration, and atrophic eyeballs.
PMID- 24353721
TI - Comparing the effects of low-dose contraceptive pills to control dysfunctional
uterine bleeding by oral and vaginal methods.
AB - Background and Objective : Contraceptive pills are generally taken orally and can
cause side effects such as nausea, vomiting and hypertension. The vaginal use of
these pills can reduce such complications. Our objective was to compare the
efficacy and side effects of low dose contraceptive pills by oral and vaginal
route in the management of dysfunctional uterine bleeding-(DUB) Methods: This
comparative observational study was conducted at Beheshti and Alzahra (SA)
teaching hospitals, affiliated to Isfahan University of Medical Sciences in 2010
2011. One hundred women who presented with DUB were randomly assigned into two
groups of equal number, receiving the low dose oral contraceptive pills by oral
or vaginal route for three month. The amount and duration of bleeding were
compared at the beginning and at the end of the study and side effects by these
two methods compared. RESULTS: The results of this study showed that both oral
and vaginal routes effectively reduced the duration and amount of bleeding due to
DUB after three courses of treatment. This effect was better in the vaginal
method compared with oral administration (P = 0.03). Regarding the side effects,
nausea and vomiting were significantly higher in the oral group than in the
vaginal group (P = 0.03). Vulvovaginitis infection was more frequent in the
vaginal group than in the oral group (P = 0.03). CONCLUSION: Low dose
contraceptive pills are effective in reducing the amount, time, and duration of
bleeding in patients with DUB. In addition, reduction of gastrointestinal side
effects by vaginal route helps to use these pills by the patient with proper
training of physicians, midwives and patients.
PMID- 24353722
TI - Impact of Training on General Practitioner's Knowledge, Attitude and Practices
Regarding Emergency Contraception in Hyderabad.
AB - OBJECTIVES: To elaborate the impact of family planning training on general
practitioners' knowledge, attitude and practices regarding emergency
contraception. METHODS: A cross sectional survey involving 270 general
practitioners was conducted in Hyderabad from 1(st) Oct to 31(st) Dec 2010.
Participants were divided into two groups on the basis of attending family
planning training course after graduation and were interviewed face to face. Data
was noted on questionnaire asking their knowledge, attitude and practices
regarding emergency contraception. Data was analyzed on SPSS version 11. Student
t-test was applied to compare the proportions among two groups. RESULTS: Out of
270 general practitioners, male & female participants were 132 (48.9%) and 138
(51.1%) respectively. Mean experience as private general practitioner was 7.48 +
7.6 years. One third of the participants 84 (31.1%) have attended five days
training course on family planning in the past, while 186 (69.9%) did not have
any training. Source of training was government institutes 46(17%) and non
government organization in 38 (14.1%) cases. Significant positive difference was
noted on emergency contraception knowledge, attitude and use in group who
attended family planning training. CONCLUSION: Educational intervention has a
positive impact on health care provider's knowledge, attitude and practices of
emergency contraception.
PMID- 24353723
TI - Can ratio of blood/curettage material HCG be used as a reliable method for
differentiating miscarriage and ectopic pregnancy?
AB - Objective : There is an increasing rate of ectopic pregnancy with the use of
assisted reproductive techniques. There is currently no serum test to
differentiate ectopic pregnancy from miscarriage. Early and accurate detection of
ectopic pregnancy may prevent the development of complications. The aim of this
study was whether the ratio of serum/curettage material hCG could provide us with
reliable and early diagnosis in distinguishing miscarriage and ectopic
pregnancies and also to measure the diagnostic accuracy rate of this method.
METHODS: A total of 24 patients were evaluated. Twelve of them were diagnosed as
an ectopic pregnancy and 12 of them were diagnosed as a miscarriage. All the
patients' diagnoses were confirmed pathologically. Non-of the patient had viable
fetus. All participants underwent curettage protocol. Serum and curettage
material were obtained at the same time. HCG measurements were done from blood
and curettage material. RESULTS: Ratio of Blood/Curettage Material HCG provides
fast and reliable results within a few hours with 91.7% accuracy rates.
CONCLUSION: Ratio of blood/curettage material HCG can be used as a reliable
method for differentiating ectopic pregnancy and miscarriage.
PMID- 24353724
TI - Outcome of conventional IVF and ICSI on sibling oocytes in moderate
ligoasthenozoospermia.
AB - OBJECTIVE: To evaluate the outcomes of patients with moderate
oligoasthenozoospermia treated with conventional in vitro fertilization (IVF) and
intracytoplasmic sperm injection (ICSI). METHODS: A total of 99 couples with
moderate oligoasthenozoospermia undergoing their first IVF/ICSI cycle were
included in the study. Sibling oocytes were randomized to be inseminated either
by conventional IVF or ICSI. Fertilization rate, cleavage rate, embryo quality,
implantation rate, and clinical pregnancy rate were examined. RESULTS: There was
no difference in the fertilization rate, cleavage rate, implantation rate, and
pregnancy rate between conventional IVF and ICSI (P>0.05). The good quality
embryo rate was significant difference between after IVF and after ICSI (P<0.05).
CONCLUSIONS: Couples with moderate oligoasthenozoospermia did not influence the
major indices of IVF and the uncertainties concerning the safety of ICSI, couples
with moderate oligoasthenozoospermia need not be subjected to ICSI.
PMID- 24353725
TI - The association of XPG and MMS19L polymorphisms response to chemotherapy in
osteosarcoma.
AB - OBJECTIVE: To assess the role of XPG, XPC, CCNH and MMS19L polymorphisms response
to chemotherapy in osteosarcoma, and the clinical outcome of osteosarcoma.
METHODS: One hundred and sixty eight osteosarcoma patients who were
histologically confirmed were enrolled in our study between January 2007 and
March 2009. Genotyping of XPG, XPC, CCNH and MMS19L was performed in a 384-well
plate format on the MassARRAY(r) platform. RESULTS: Individuals with rs2296147 TT
genotype showed a better response as compared with CC genotype, with the OR (95%
CI) of 3.89(1.49-10.95). Those carrying rs29001322 TT genotype presented better
response to chemotherapy, and the OR (95% CI) was as high as 12.25(2.63-121.84).
Patients carrying TT genotype of XPG rs2296147 and MMS19L rs29001322 showed a
significantly longer overall survival than CC genotype, they had 0.37 and 0.31
fold risk of death when compared with wide-type of this gene. CONCLUSIONS: XPG
rs2296147 and MMS19L rs29001322 are correlated with response to chemotherapy and
prognosis of osteosarcoma. Our findings would provide important evidence for
prognostic and therapeutic implications in osteosarcoma.
PMID- 24353726
TI - Morbidity associated with treatment of chronic anal fissure.
AB - OBJECTIVE: To assess the effectiveness of different modes of treatment of chronic
anal fissure as regards improvement of symptoms and complications. METHODS: This
prospective study included 129 consecutive patients with chronic anal fissures
presented to the Surgical Outpatients' Department of Islam Teaching Hospital
Sialkot, Pakistan; from September 2010 to November 2012. Patients were
distributed in three groups. In "OBG group", patients had attended Gynae/Obs OPD
and got treated and were then referred to surgical OPD for failure of treatment
or recurrence. Patients who presented with history of treatment by GPs were
included in "GP Group" "SGR Group" included those who directly reported to
surgical OPD for treatment. Patients were managed both pharmacologically as OPD
patients and surgically as admitted patients. Patients were instructed to apply
small amounts of 0.2% GTN paste in soft white paraffin, to the anoderm with
finger tips three times a day. Patients were evaluated at two-week intervals and
at each visit the symptoms control, adverse effects and fissure status were
recorded. If there was symptomatic relief or the fissure healing was in progress,
the treatment was continued for a total duration of eight weeks. Operated
patients were nursed in wards after surgery i.e Internal Anal Sphicterotomy. They
were advised to report to OPD weekly for one month or earlier if they experienced
any symptoms suggestive of complications. Patients were declared cured in case of
complete symptomatic relief with fissure healing. Success, failure and associated
problems were recorded and analysed to get results. RESULTS: This study included
129 patients who could be followed up for a minimum of three months. These
patients were referred by gynaecologist i.e. 22 (17%) for treatment failure while
5 patients with wrong diagnosis were not included in statistical analysis;
similarly 41 (32%) patients were referred by general practitioners and 9 patients
with wrong diagnosis were excluded. Sixty six patients i.e. 51% were those who
directly reported to surgical OPD and had no previous treatment. With surgical
treatment, pain, bleeding per rectum and constipation showed significant
improvement as compared to GTN ointment application. Fissure healing was 100% in
surgical group as compared to 74% in medical group. Complications were recorded
and were found to be headache with medical treatment; while the most feared
complication with surgical treatment i.e. permanent incontinence was not
encountered in our study. CONCLUSION: Topical glyceryl trinitrate is economical,
has a good healing rate, and faecal incontinence has not been reported. Its
effectiveness, however, depends on patients' compliance which may be poor in view
of associated headaches and a local burning sensation. It is first line of
treatment for anal fissure but lateral internal sphincterotomy is superior, more
effective and curative than the chemical sphincterotomy. Surgery is reserved for
people with anal fissure who have tried medical therapy for at least one to three
months but failed.
PMID- 24353727
TI - Outcome and Complications of Endoscopic Dacryocystorhinostomy without Stenting.
AB - OBJECTIVES: To determine the outcome and complications of endoscopic
dacryocystorhinostomy without stenting at Ziauddin University Hospital, Keamari,
Karachi, Pakistan. METHODOLOGY: Fifty Patients who underwent endoscopic
dacryocystorhinostomy from August 2011 to July 2012 at Department of
Ophthalmology, Ziauddin University Hospital, Keamari, Karachi were included.Data
regarding the Outcomes and complications were collected and analyzed. RESULTS:
Among the 50 patients there were 38%(n=19) males and 62%(n=31) females.Their age
ranged from 15 to 60 years, mean age was 43.54 +/- 9.36 years. Majority of
patients were in the age ranging from 31 to 50 years. The success rate after 6
months of surgery was 92% without any significant complications. CONCLUSION:
Endoscopicdacryocystorhinostomy without stent is minimally invasive technique
with less complications and good success state. In addition it gives no facial
scar.
PMID- 24353728
TI - The prevalence of disorders causing disability in young adult males in Turkey
between 2009-2011.
AB - OBJECTIVE: Disability is one of the significant problems that the public faces as
regards social aspects, economics, public health and politics. Our aim was to
review the prevalence of diseases causing disabilities in young adult men who are
declared "unfit for military service" in Turkey after medical examination.
METHODS: We reviewed the prevalence of diseases among 113,175 young adult men who
were referred for medical examination between 2009 and 2011. RESULTS: Prevalence
of unfitness for military service was 5.56% in 2009, 6.74% in 2010 and 6.77% in
2011. Leading causes for young adult men to be rejected from military service was
intellectual disability 6.88, hearing loss 3.71, epilepsy 1.59, schizophrenia
1.54 and diabetes mellitus 1.47 per thousand people. CONCLUSION: Screening for
the prevalence of disability conditions is an important data source for policies
to be developed. Supporting such survey with community based studies in different
populations in future shall be beneficial for improvement of policies in social
and health fields.
PMID- 24353729
TI - Nosocomial Acinetobacter baumannii Infections and Changing Antibiotic Resistance.
AB - OBJECTIVES: In the intensive care setting, Acinetobacter baumannii causes
ventilator-associated pneumonia and other nosocomial infections that are
difficult to treat. Objective of this study was to investigate nosocomial A.
baumannii infections and its changing antibiotic resistance. METHODS: A total of
56 patients diagnosed with A.baumannii infections between January 2009 and
December 2011 were included in the study. Diagnosis for nosocomial infections was
established according to the CDC (Centers for Disease Control and Prevention)
criteria. Identification of the agents isolated was carried out using
conventional methods and VITEK 2 automated system, while antibiotic sensitivity
testing was performed through VITEK 2 AST-N090 automated system. RESULTS: The
most common infection was nosocomial pneumonia by 43%, among which 46% were
ventilator-associated pneumonia. Considering all years, the most effective
antibiotics on the isolated strains were found as colistin, tigecycline, imipenem
and meropenem. However resistance to imipenem and meropenem was observed to
increase over years. CONCLUSION: The issue of increased resistance to antibiotics
poses difficulty in treatment of A. baumannii infections which in turn increases
the rate of mortality and cost. In order to prevent development of resistance,
antibiotics must be used in an appropriate way in accompanied with proper
guidance.
PMID- 24353730
TI - Determination of site-specific carotid-intima media thickness: common -carotid
artery and carotid bifurcation in hypercholesterolemia patients.
AB - OBJECTIVE: To determine site specific carotid intima-media thickness: common
carotid artery and carotid bifurcation in hypercholesterolemia patients as a
marker for atherosclerosis. METHODS: Fifty patients with hypercholesterolemia and
twenty controls were selected after getting informed consent regarding the
investigation of carotid- intima media thickness by B-mode ultrasound. All the
patients of hypercholesterolemia with LDL-C > 160mg/dL had family history of
coronary artery diseases. This procedure was carried out in the Radiology
Department of Dr. Ziauddin Hospitals. Measurement of carotid -intima media
thickness, B-mode ultrasonography of common carotid artery, carotid bifurcation
and internal carotid artery (left and right carotid arteries) was performed with
Toshiba (M# SSA-580A/E2) ultrasound scanner with linear probe. The posterior or
far wall of the carotid artery is, the distance between the leading edge first
bright line (lumen -intima interface) and the leading edge of the second bright
line (media-adventitia interface) of far wall was recorded as intima -media
thickness. The average mean of six segments of intima-media thickness was taken
as mean CIMT of right and left common carotid, bifurcation and internal carotid
arteries. RESULTS: Maximal CIMT was significantly increased at sites common
carotid, carotid bifurcation and internal carotid arteries in fifty patients with
hypercholesterolemia as compared to controls. At carotid bifurcation mean of
maximal CIMT was (0.9+ 0.3mm). Range of maximum CIMT in hypercholesterolemia
patients was (0.8- 3.3mm) and in controls (0.4- 0.8 mm). The thickness was more
frequently increased at site of bifurcation. CONCLUSIONS: Carotid intima- media
thickness in hypercholesterolemia patients was increased and carotid bifurcation
was site that has shown greater increase in intima-media thickness and plaques in
these patients predict high risk for atherosclerosis.
PMID- 24353731
TI - Prevalence of multi drug resistant Acinetobacter baumannii in the clinical
samples from Tertiary Care Hospital in Islamabad, Pakistan.
AB - BACKGROUND & OBJECTIVES: Acinetobacter baumannii can cause a wide range of
infections, including bacteremia, pneumonia, urinary tract infection,
peritonitis, etc. This organism is becoming resistant to a large group of
antibiotics, especially beta-lactam antibiotics. The reason for multi-drug
resistance may be the production of extended- spectrum beta-lactamses (ESBLs),
carbapenemases/metallo beta-lactamases or AmpC beta-lactamases. The aim of the
present study was to determine the prevalence of multi-drug resistant
Acinetobacter baumannii isolated from the patients in Surgical Intensive Care
Units (SICUs) of Pakistan Institute of Medical Sciences (PIMS), Islamabad,
Pakistan. METHODS: A total of 91 A. baumanni isolates were collected from PIMS
during the period from February 2011 to December 2011. The antibiotic
susceptibility testing was performed by standard disc diffusion method as
recommended by CLSI. Combination disc method, Modified Hodge test, EDTA disc
synergy test and AmpC disc test were performed for detection of ESBLs,
carbapenemases, metallo beta-lactamases, and AmpC beta-lactamases, respectively.
RESULTS: The prevalence of MDRs was reported 100% among A. baumannii. The
antibiotic susceptibility profile showed that minocycline and tigecycline were
the most effective drugs against A. baumannii. Almost all of A. baumannii
isolates were carbapenemase and metallo beta-lactamase producers. AmpC prevalence
was observed in 41.76%, while none of the isolates was ESBL producer. Antibiogram
and minimal inhibitory concentrations (MICs) indicated tetracycline is relatively
effective against A. baumanii. CONCLUSIONS: Increased frequency of multi-drug
resistance supports the need for continuous surveillance to determine prevalence
and evolution of these enzymes in Pakistan.
PMID- 24353732
TI - Effect of Nicotinic Acid (Vitamin B3 or Niacin) on the lipid profile of diabetic
and non - diabetic rats.
AB - OBJECTIVE: To determine the efficacy of nicotinic acid on the lipid profile of
diabetic and non diabetic rats. METHODS: This was an experimental study done at
the Institute of Molecular Biology and Biotechnology, The University of Lahore,
Pakistan between May 2010 to July 2010. Nicotinic acid was administered to a
hypercholesterolemic group and a hypercholesterolemic + diabetic Group of Albino
rats for 42 days and response to therapy was recorded on day 21 and day 42 of the
experiment. Comparison among these two groups as well as three control groups was
determined by Analysis of Variance (ANOVA) and differences were considered
significant at (P<0.05). A total of 50 rats were included in the study. RESULTS:
Lipid profile of the hypercholesterolemic group as well as hypercholesterolemic +
diabetic group as compared with the control groups showed highly significant
improvement on the day 21 and day 42 of the experiment. The values of serum total
cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) cholesterol
and total lipids (TL) showed highly significant decrease whereas serum high
density lipoprotein (HDL) cholesterol showed highly significant increase.
CONCLUSION: Nicotinic acid is the most effective agent available in increasing
HDL cholesterol and lowering serum TC, triglycerides (TG), LDL cholesterol and TL
in hypercholesterolemic Diabetic and hypercholesterolemic non-diabetic Albino
rats.
PMID- 24353733
TI - Effectiveness of the Primary Trauma Care Course: Is the outcome satisfactory?
AB - OBJECTIVE: To assess the improvement of knowledge and skills of trauma management
among participant of Primary Trauma Care (PTC) workshop. METHODS: A two days
Primary Trauma Care (PTC) provider workshop was organized at Dow International
Medical College, Karachi - Pakistan on March 5(th) and 6th 2011. Participant's
knowledge was assessed by 30 Best Choice Questions (BCQs) and their trauma
management skills were assessed by management of trauma case scenario both at pre
and post workshop. All scenarios performed by participants were video recorded
and marked on a 20 points check list and evaluated by two PTC trainers and graded
after consensus. Percentage of participants who scored more than 70% marks on
knowledge and skills component were also analyzed. Data was analyzed by SPSS
version 17. Wilcoxon Sign Rank test was used to find out significant difference
between pre and post workshop score. RESULTS: A total of 20 participants attended
the full workshop. Median One best question score before the workshop was 19.5
and post workshop was 25 (p<0.0001). Trauma skills scenario score also showed
marked improvement with median score of 3.5 pre workshop and 9.5 post workshop
(p<0.0001). Total 19 participants had >=70% post workshop knowledge score.
However, only 4 participants had trauma skill score with >=70 marks. CONCLUSION:
Primary Trauma Care workshop could be an effective course for gaining of
knowledge and skills of initial management of trauma patients. However, some
modifications need to be done for training of skills components to maximize the
output of this interactive workshop.
PMID- 24353735
TI - Burkholderia cepacia septicemia in a patient with acute myeloid leukemia in
postchemotherapy bone marrow aplasia.
AB - The patients with hematologic malignancies are predisposed to develop infections
with unusual bacteria, like Burkholderia cepacia, which is frequently resistant
to many antibiotics and antiseptics. We present the case of a female patient with
acute myeloid leukemia type 2 on the background of myelodysplastic syndrome, from
whom Burkholderia cepacia was isolated in blood culture, after the 2(nd) cycle of
induction. She was sensitive to ceftazidime, but its eradication was not easy.
Five other patients were contaminated with this bacteria, but all of them had
favourable evolution. The case is discussed in the context of those similar in
literature.
PMID- 24353734
TI - Meta-Analysis of ABCB1 3435C>T Polymorphism and Colorectal Cancer.
AB - OBJECTIVE: Many studies have focused on the association between the ABCB1 3435C>T
polymorphism and colorectal cancer (CRC) risk. However, the results were
conflicting. The aim of this meta-analysis is to evaluate the precise association
between this polymorphism and CRC risk. METHODS: We formally reviewed the
literature at Pubmed, EMBASE and the Cochrane Library with the key words as
follows: ABCB1/MDR1/P-glycoprotein, polymorphism, colorectal and
cancer/neoplasm/tumor. This meta-analysis was assessed by Review manager 5.0. The
fixed-effects model was used to pool the odds ratios (OR) with 95% confidence
intervals (CI) for CRC risk. RESULTS: There were 8 studies identified. The pooled
OR with 95% CI of CC+CT versus TT genotype of the ABCB1 3435C>T polymorphism for
CRC risk was 1.01 [0.90-1.13]. The sensitivity analysis further confirmed the
result. Heterogeneity and publication bias were not observed in this meta
analysis. CONCLUSIONS: In summary, there was no significant association between
the ABCB1 3435C>T polymorphism and CRC risk. Abbreviations used: the ATP-binding
cassette, subfamily B, member 1 (ABCB1); multidrug resistance gene 1 (MDR1); P
glycoprotein (P-gp); colorectal cancer (CRC); single nucleotide polymorphisms
(SNPs); odds ratio (OR); confidence interval (CI); Hardy-Weinberg equilibrium
(HWE).
PMID- 24353736
TI - Erlotinib and gefitinib treatments of the lung cancer in an elderly patient
result in gastrointestinal bleeding.
AB - Lung cancer is currently one of the leading causes of the cancer-related deaths
in the world. Erlotinib and Gefitinib are inhibitors of human epidermal growth
factor receptor-1 and the epidermal growth factor receptor tyrosine kinase. The
most common adverse events for erlotinib and gefitinib were mild to moderate skin
toxicity (rash, itching, and dry skin), gastrointestinal reactions (diarrhea and
nausea), and fatigue. Erlotinib induced gastrointestinal bleeding is rare, and
dose-related. We are reporting a lung cancer patient who received erlotinib and
gefitinib. The patient was sensitive to drug and tumor growth was inhibited.
However, adverse reactions appeared as drug treatment continued, including
gastrointestinal bleeding.
PMID- 24353737
TI - Montelukast as a successful treatment for eosinophilic cystitis in an asthmatic
woman patient.
AB - Eosinophilic cystitis (EC) is a rare inflammatory disorder. We herein report a
case of EC in an asthmatic female patient who had a recent exacerbation with none
known allergen. She was administered montelukast sodium orally for four weeks and
received complete remission. This medication was successfully discontinued after
a three-month follow up period. This case report about successful treatment of an
adult EC patient using montelukast sodium may provide a new option for EC
patients with allergic history.
PMID- 24353738
TI - Complete traumatic fracture-dislocation L3-L4 of the lumbar spine.
AB - Complete traumatic fracture-dislocation of the lumbar spine is a rare spinal
injury often leading to death. Surgical intervention is an effective treatment
modality to decrease mortality. Our patient was a 16 year old boy who had a
collision caused by fall from a construction material lifter. He was referred to
our hospital with waist trauma. Later, the patient underwent posterior surgical
decompression during which vertebral column restoration by long segment fixation
was performed. After surgery there were no significant changes in the patient
condition.
PMID- 24353739
TI - Left main coronary artery spasm in a hyperthyroid patient with suspected acute
coronary syndrome.
AB - The left main coronary artery (LMCA) vasospasm is rare. We report a suspected
acute coronary syndrome patient with hyperthyroidism who had LMCA vasospasm.
Coronary angiogram showed 60% stenosis at LMCA. After administering
nitroglycerin, re-angiography showed no significant stenosis. Then we evaluated
LMCA lesion using intravascular ultrasound (IVUS) showing no significant
stenosis. We considered that it was a LMCA vasospasm and may be assosiated with
hyperthyroid state. After anti-thyroid and anti-spasm treatment, chest pain
subsided. In conclusion, hyperthyroidism induced coronary hypersensitivity may
contribute to LMCA vasospasm as seen in this case. IVUS may be useful to identify
coronary vasospasm.
PMID- 24353740
TI - An 85-year-old woman with Miller Fisher syndrome.
AB - Miller Fisher's syndrome (MFS) commonly presents in the fourth and fifth decades
and are rare in people over 70 years. An 85-year-old female with no significant
medical history presented with upper extremity anesthesia, ptosis, and unsteady
gait. The patient had a history of hypertension and diabetes mellitus. Physical
examination showed bilateral total external ophthalmoplegia, areflexia, and
cerebellar ataxia. Radiological and laboratory studies were unremarkable. Lumbar
puncture showed albuminocytological dissociation. The combined history, physical
examination, and lumbar puncture results established a presumptive diagnosis of
MFS. Intravenous immunoglobulin was given for 5 days. The patient gradually
improved 10 days after the onset of symptoms. Ophthalmoplegia had fully recovered
after 6 months. To the best of our knowledge, this case represented the oldest
patient with MFS.
PMID- 24353741
TI - What can cardiac magnetic resonance do for cardiologists in China?
PMID- 24353742
TI - Descriptive epidemiology of ophthalmic and ocular adnexal non-Hodgkin's lymphoma.
AB - In this article, we provide an update on incidence rates of ophthalmic non
Hodgkin's lymphoma (NHL), in the context of other NHL, in the USA. We also
provide population-based estimates of incidence and survival for ocular adnexal
NHL, the most common form of ophthalmic NHL, for which descriptive patterns have
not been previously reported. Ophthalmic and ocular adnexal NHL have unique
incidence patterns, including equal rates among both genders, predominance among
Asians/Pacific Islanders, and steady and rapid increases in the past few decades.
Studies of international variations in the incidence of ocular adnexal NHL may
provide clues as to the underlying mechanisms influencing its unique
epidemiology.
PMID- 24353743
TI - In vivo three-photon microscopy of subcortical structures within an intact mouse
brain.
AB - Two-photon fluorescence microscopy (2PM)1 enables scientists in various fields
including neuroscience2,3, embryology4, and oncology5 to visualize in vivo and ex
vivo tissue morphology and physiology at a cellular level deep within scattering
tissue. However, tissue scattering limits the maximum imaging depth of 2PM within
the mouse brain to the cortical layer, and imaging subcortical structures
currently requires the removal of overlying brain tissue3 or the insertion of
optical probes6,7. Here we demonstrate non-invasive, high resolution, in vivo
imaging of subcortical structures within an intact mouse brain using three-photon
fluorescence microscopy (3PM) at a spectral excitation window of 1,700 nm.
Vascular structures as well as red fluorescent protein (RFP)-labeled neurons
within the mouse hippocampus are imaged. The combination of the long excitation
wavelength and the higher order nonlinear excitation overcomes the limitations of
2PM, enabling biological investigations to take place at greater depth within
tissue.
PMID- 24353744
TI - A Virtual Environment for People Who Are Blind - A Usability Study.
AB - For most people who are blind, exploring an unknown environment can be
unpleasant, uncomfortable, and unsafe. Over the past years, the use of virtual
reality as a learning and rehabilitation tool for people with disabilities has
been on the rise. This research is based on the hypothesis that the supply of
appropriate perceptual and conceptual information through compensatory sensorial
channels may assist people who are blind with anticipatory exploration. In this
research we developed and tested the BlindAid system, which allows the user to
explore a virtual environment. The two main goals of the research were: (a)
evaluation of different modalities (haptic and audio) and navigation tools, and
(b) evaluation of spatial cognitive mapping employed by people who are blind. Our
research included four participants who are totally blind. The preliminary
findings confirm that the system enabled participants to develop comprehensive
cognitive maps by exploring the virtual environment.
PMID- 24353745
TI - Crosswatch: a System for Providing Guidance to Visually Impaired Travelers at
Traffic Intersections.
AB - PURPOSE: This paper describes recent progress on the "Crosswatch" project, a
smartphone-based system developed for providing guidance to blind and visually
impaired travelers at traffic intersections. Building on past work on Crosswatch
functionality to help the user achieve proper alignment with the crosswalk and
read the status of walk lights to know when it is time to cross, we outline the
directions Crosswatch is now taking to help realize its potential for becoming a
practical system: namely, augmenting computer vision with other information
sources, including geographic information systems (GIS) and sensor data, and
inferring the user's location much more precisely than is possible through GPS
alone, to provide a much larger range of information about traffic intersections
to the pedestrian. DESIGN/METHODOLOGY/APPROACH: The paper summarizes past
progress on Crosswatch and describes details about the development of new
Crosswatch functionalities. One such functionality, which is required for
determination of the user's precise location, is studied in detail, including the
design of a suitable user interface to support this functionality and preliminary
tests of this interface with visually impaired volunteer subjects. FINDINGS: The
results of the tests of the new Crosswatch functionality demonstrate that the
functionality is feasible in that it is usable by visually impaired persons.
RESEARCH LIMITATIONS/IMPLICATIONS: While the tests that were conducted of the new
Crosswatch functionality are preliminary, the results of the tests have suggested
several possible improvements, to be explored in the future. PRACTICAL
IMPLICATIONS: The results described in this paper suggest that the necessary
technologies used by the Crosswatch system are rapidly maturing, implying that
the system has an excellent chance of becoming practical in the near future.
ORIGINALITY/VALUE: The paper addresses an innovative solution to a key problem
faced by blind and visually impaired travelers, which has the potential to
greatly improve independent travel for these individuals.
PMID- 24353746
TI - Factors causing sex differences in birds.
AB - In recent years, increasing evidence suggests that sex differences in the
phenotype of all tissues is influenced by the inequality of effects of sex
chromosome genes in the two sexes. In birds, genes on the Z chromosome are not
well dosage compensated, so that most Z genes are expressed higher in ZZ male
cells than in ZW female cells. The sex difference in expression of Z and W genes
is likely to cause sex differences within cells, in addition to the sex
differences caused by different levels of testicular and ovarian hormones. The
sexual imbalance in cell physiology has implications for aviculture and novel
developments in the poultry industry.
PMID- 24353748
TI - Decreasing Levels of the cdk5 Activators, p25 and p35, Reduces Excitotoxicity in
Striatal Neurons.
AB - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by
an expanded CAG trinucleotide repeat sequence in the huntingtin gene. The
resulting poly-glutamine expansion in the huntingtin protein imparts a novel
toxic gain of function causing selective loss of medium spiny neurons (MSNs) in
the striatum. Although the exact mechanism of cell death is unclear, recent
evidence suggests involvement of NMDA-receptor mediated excitotoxicity and
aberrant cyclin dependent kinase 5 (cdk5) activity in striatal cells undergoing
neurodegeneration. In this study we directly tested the effect of reduced levels
of p25 and p35, two proteins required for cdk5 activation, on striatal
neurodegeneration using mice with targeted deletion of p35. Quinolinic acid (QA)
injected into the striatum of mice causes NMDA-receptor mediated cell death, and
these QA-induced striatal lesions were examined in p35 hemizygous null (p35+/-)
and wildtype (WT) mice. Striatal QA lesion volumes were 30% smaller in p35+/-
mice than in WT mice. Furthermore, primary neuronal cultures of MSNs from P0
p35+/- pups displayed 33% less apoptotic neurons following NMDA treatment than
those from WT pups. Examination of YAC128 mouse model of HD showed elevated p25
levels in striatum following intrastriatal QA injection. Our findings provide
direct evidence for p25 and p35 involvement in excitotoxic neurodegeneration of
MSNs and suggest a role for the cdk5 pathway in HD striatal neurodegeneration.
PMID- 24353749
TI - A Magnetic Resonance-Compatible Loading Device for Dynamically Imaging Shortening
and Lengthening Muscle Contraction Mechanics.
AB - The purpose of this study was to design and test a magnetic resonance (MR)
compatible device to induce either shortening or lengthening muscle contractions
for use during dynamic MR imaging. The proposed device guides the knee through
cyclic flexion-extension, while either elastic or inertial loads are imposed on
the hamstrings. Ten subjects were tested in a motion capture laboratory to
evaluate the repeatability of limb motion and imposed loads. Image data were
subsequently obtained for all ten subjects using cine phase contrast imaging.
Subjects achieved ~30 deg of knee joint motion, with individual subjects
remaining within ~1 deg of their average motion across 56 repeated cycles. The
maximum hamstring activity and loading occurred when the knee was flexed for the
elastic loading condition (shortening contraction), and extended for the inertial
loading condition (lengthening contraction). Repeat MR image acquisitions of the
same loading condition resulted in similar tissue velocities, while spatial
variations in velocity data were clearly different between loading conditions.
The proposed device can enable dynamic imaging of the muscle under different
types of loads, which has the potential to improve our understanding of basic
muscle mechanics, identify potential causes of muscle injury, and provide a basis
for quantitatively assessing injury effects at the tissue level. Slight
modifications to the device design and/or subject positioning could allow for
imaging of the quadriceps or the knee.
PMID- 24353752
TI - Simulating the dynamics of scale-free networks via optimization.
AB - We deal here with the issue of complex network evolution. The analysis of
topological evolution of complex networks plays a crucial role in predicting
their future. While an impressive amount of work has been done on the issue, very
little attention has been so far devoted to the investigation of how information
theory quantifiers can be applied to characterize networks evolution. With the
objective of dynamically capture the topological changes of a network's
evolution, we propose a model able to quantify and reproduce several
characteristics of a given network, by using the square root of the Jensen
Shannon divergence in combination with the mean degree and the clustering
coefficient. To support our hypothesis, we test the model by copying the
evolution of well-known models and real systems. The results show that the
methodology was able to mimic the test-networks. By using this copycat model, the
user is able to analyze the networks behavior over time, and also to conjecture
about the main drivers of its evolution, also providing a framework to predict
its evolution.
PMID- 24353747
TI - Multimodal Nonlinear Optical Microscopy.
AB - Because each nonlinear optical (NLO) imaging modality is sensitive to specific
molecules or structures, multimodal NLO imaging capitalizes the potential of NLO
microscopy for studies of complex biological tissues. The coupling of multiphoton
fluorescence, second harmonic generation, and coherent anti-Stokes Raman
scattering (CARS) has allowed investigation of a broad range of biological
questions concerning lipid metabolism, cancer development, cardiovascular
disease, and skin biology. Moreover, recent research shows the great potential of
using CARS microscope as a platform to develop more advanced NLO modalities such
as electronic-resonance-enhanced four-wave mixing, stimulated Raman scattering,
and pump-probe microscopy. This article reviews the various approaches developed
for realization of multimodal NLO imaging as well as developments of new NLO
modalities on a CARS microscope. Applications to various aspects of biological
and biomedical research are discussed.
PMID- 24353753
TI - Factors affecting regional per-capita carbon emissions in China based on an LMDI
factor decomposition model.
AB - China is considered to be the main carbon producer in the world. The per-capita
carbon emissions indicator is an important measure of the regional carbon
emissions situation. This study used the LMDI factor decomposition model-panel co
integration test two-step method to analyze the factors that affect per-capita
carbon emissions. The main results are as follows. (1) During 1997, Eastern
China, Central China, and Western China ranked first, second, and third in the
per-capita carbon emissions, while in 2009 the pecking order changed to Eastern
China, Western China, and Central China. (2) According to the LMDI decomposition
results, the key driver boosting the per-capita carbon emissions in the three
economic regions of China between 1997 and 2009 was economic development, and the
energy efficiency was much greater than the energy structure after considering
their effect on restraining increased per-capita carbon emissions. (3) Based on
the decomposition, the factors that affected per-capita carbon emissions in the
panel co-integration test showed that Central China had the best energy structure
elasticity in its regional per-capita carbon emissions. Thus, Central China was
ranked first for energy efficiency elasticity, while Western China was ranked
first for economic development elasticity.
PMID- 24353754
TI - PombeX: robust cell segmentation for fission yeast transillumination images.
AB - Schizosaccharomyces pombe shares many genes and proteins with humans and is a
good model for chromosome behavior and DNA dynamics, which can be analyzed by
visualizing the behavior of fluorescently tagged proteins in vivo. Performing a
genome-wide screen for changes in such proteins requires developing methods that
automate analysis of a large amount of images, the first step of which requires
robust segmentation of the cell. We developed a segmentation system, PombeX, that
can segment cells from transmitted illumination images with focus gradient and
varying contrast. Corrections for focus gradient are applied to the image to aid
in accurate detection of cell membrane and cytoplasm pixels, which is used to
generate initial contours for cells. Gradient vector flow snake evolution is used
to obtain the final cell contours. Finally, a machine learning-based validation
of cell contours removes most incorrect or spurious contours. Quantitative
evaluations show overall good segmentation performance on a large set of images,
regardless of differences in image quality, lighting condition, focus condition
and phenotypic profile. Comparisons with recent related methods for yeast cells
show that PombeX outperforms current methods, both in terms of segmentation
accuracy and computational speed.
PMID- 24353755
TI - Water Adsorption at the Tetrahedral Titania Surface Layer of SrTiO3(110)-(4 * 1).
AB - The interaction of water with oxide surfaces is of great interest for both
fundamental science and applications. We present a combined theoretical (density
functional theory (DFT)) and experimental (scanning tunneling microscopy (STM)
and photoemission spectroscopy (PES)) study of water interaction with the two
dimensional titania overlayer that terminates the SrTiO3(110)-(4 * 1) surface and
consists of TiO4 tetrahedra. STM and core-level and valence band PES show that
H2O neither adsorbs nor dissociates on the stoichiometric surface at room
temperature, whereas it does dissociate at oxygen vacancies. This is in agreement
with DFT calculations, which show that the energy barriers for water dissociation
on the stoichiometric and reduced surfaces are 1.7 and 0.9 eV, respectively. We
propose that water weakly adsorbs on two-dimensional, tetrahedrally coordinated
overlayers.
PMID- 24353757
TI - ENGAGING THE COMMUNITY IN HEALTH RESEARCH IN INDIA.
AB - Community-engaged research approaches involve members of the community in various
aspects of a research endeavor to improve the health of populations. Engaging the
community in research is important in the development, dissemination, and
evaluation of new interventions, technologies, and other medical advancements to
improve population health globally. A review of published community-engaged
research studies conducted in India was performed. Fifteen published studies were
identified and reviewed to evaluate the state of community-engaged research in
India. The review indicated that community-engaged research in India is limited.
Most published community-engaged research focused on health promotion, especially
in the prevention or management of HIV/AIDS and other STIs. Community members
were involved in a variety of aspects of the research, but there was not one
published article indicating that community members had defined the disease of
focus. Community-engaged research often led to valuable insights into the views,
experiences, and behaviors of community members and also led to increased
community participation in health initiatives. It is anticipated that future
community-engaged research will lead to improvements in global health through
increased empowerment of communities and a better ability to implement new and
innovative medical advances, technologies, and interventions.
PMID- 24353758
TI - Tongue ulcer in a case of X-linked diskeratosis congenita.
PMID- 24353759
TI - Treatment of post-surgical scars of cheek's mucosa with Er, Cr: YSGG laser.
PMID- 24353760
TI - Management of burning mouth syndrome: a clinical experience.
PMID- 24353761
TI - An unusual lesion of the palate.
PMID- 24353762
TI - Mithocondrial DNA analysis in a case of multiple oral carcinomas following
allogenic hematopoietic stem cell transplantation.
PMID- 24353763
TI - Behcet's disease in an adolescent patient.
PMID- 24353764
TI - Low level laser therapy (LLLT) as adjuvant in the management of drug induced
gingival hyperplasia: a case report.
PMID- 24353765
TI - Oral cancer and mucosal trauma: a case series.
PMID- 24353766
TI - Pemphigus vulgaris of the oral cavity in a patient with coeliac disease:
coincidence or relationship?
PMID- 24353767
TI - Numb chin syndrome.
PMID- 24353768
TI - A strange "butterly-like" ulcer of the palate. May be it the results of an
underlying trombotic event in a predisposed patient?
PMID- 24353769
TI - Turner syndrome with dental structural abnormalities: histological and
morphostructural features by confocal laser microscopy.
PMID- 24353770
TI - An unusual lingual lesion in a little patient.
PMID- 24353771
TI - The photodynamical treatment of oral verrucous proliferative leukoplakia. Case
report at 18 months follow up.
PMID- 24353772
TI - White tongue and straight hair in a patient with chronic hepatitis C: a case
report and review of the literature.
PMID- 24353773
TI - Mandibular brown tumor as the first manifestation of primary hyperparathyroidism:
a case report.
PMID- 24353774
TI - Drug-induced gingival hyperplasia, treatment with diode laser.
PMID- 24353775
TI - Loss of p53 protein expression in leukoplakias may reveal the presence of an oral
squamous cell carcinoma: a case series analysis.
PMID- 24353776
TI - Familial Tumoral Calcinosis with dento-alveolar anomalies: clinico-pathological
findings and Confocal Laser Scanning Microscopy of hard and soft tissues lesions.
PMID- 24353777
TI - Salivary gland tumors in patients with necrotizing sialometaplasia: a case
series.
PMID- 24353778
TI - Misunderstood oral early syphilis: a meaningful case report.
PMID- 24353779
TI - A single biopsy in patients with multiple pre-malignant lesions may lead to an
inappropriate treatment: a report of two cases.
PMID- 24353780
TI - Conservative surgical treatment in the management of BRONJ: a case series of 129
consecutive cases.
PMID- 24353781
TI - LLLT in combination with non-surgical periodontal therapy in patients with
gingival oral lichen planus: a pilot study.
PMID- 24353782
TI - Osteonecrosis of the jaw related to everolimus and bisphosphonate: a unique case
report?
PMID- 24353783
TI - Oral hygiene in patients with gingival pemphigus vulgaris: a case series.
PMID- 24353784
TI - Unusual solid tumors metastasis to the oral cavity.
PMID- 24353785
TI - An unusual case of everolimus-associated recurrent oral ulcerations in heart
transplant recipient.
PMID- 24353786
TI - Rhabdomyosarcoma of the oral cavity in a 24-year-old male patient.
PMID- 24353787
TI - A rare case of (KCOT) keratocyst odontogenic tumor in association with
hypodontia.
PMID- 24353788
TI - Brain abscess of odontogenic origin: two cases report and review of the
literature.
PMID- 24353789
TI - Blandin-nuhn gland mucocele: presentation of a new case and review of the
literature.
PMID- 24353790
TI - Minimally invasive approach to eliminate pyogenic granuloma using Er, Cr: YSGG
laser.
PMID- 24353791
TI - Juvenile Nasopharyngeal Angiofibroma: diagnosis and surgical treatment in I and
II stage with dento-alveolar involvement.
PMID- 24353793
TI - The importance of differential diagnosis between Bronj and hematologic diseases.
PMID- 24353792
TI - Uncommon gingival swelling.
PMID- 24353794
TI - Maxillary peripheral calcifying epithelial odontogenic tumour (Pindborg tumor).
PMID- 24353795
TI - NK leukemia: a rare case of oral manifestations representing the initial sign.
PMID- 24353796
TI - Glandular odontogenic cyst: report of a new case with cytokeratin-19 expression.
PMID- 24353797
TI - Paraneoplastic acanthosis nigricans maligna.
PMID- 24353798
TI - Should jaws positive tracer uptake on scintigraphy be considered a new finding of
BRONJ stage 0?
PMID- 24353799
TI - Oro-Facial Lymphatic Malformation: management with a new three steps Laser
protocol.
PMID- 24353801
TI - Localized granulomatous disease involving mandibular bone and sub-mandibular
lymphnodes in a 11-year-old girl.
PMID- 24353800
TI - Oral submucosal hemorrhage as first clinical manifestation of H. Pylori
Associated Idiopathic Thrombocytopenic Purpura.
PMID- 24353802
TI - Uncommon diagnosis of Kaposi's Sarcoma in a HIV-negative adult patient.
PMID- 24353803
TI - Primary intraosseus carcinoma of the jaws arising froma odontogenic cyst - a case
report.
PMID- 24353804
TI - Epidermal nevus syndrome: epithelial and cutaneous tumours without systemic
disorders: a case report.
PMID- 24353805
TI - Idiopathic fibrous hyperplasia of the palate.
PMID- 24353806
TI - Pyogenic Granuloma: surgical treatment with Diode Laser.
PMID- 24353807
TI - Oral ulcers and chronic gastrointestinal disorders.
PMID- 24353808
TI - A case of linear IgA disease limited to the oral mucosa.
PMID- 24353809
TI - Laser-assisted surgery in oral medicine: treatment of fibrous epulis with diode
915 nm.
PMID- 24353810
TI - A case of Heck's disease treated with Quantum Molecular Resonance Scalpel.
PMID- 24353811
TI - Primary intraosseous carcinoma of the mandible arising from epithelial remnants
of odontogenic cyst.
PMID- 24353812
TI - A case series of 42 non-complaining bad breath patients and the neuropsychology
of their disease.
PMID- 24353813
TI - Severe ulceration of the tongue: first symptom of a psychiatric disorder.
PMID- 24353814
TI - Multiple melanotic macules of unknown origin.
PMID- 24353815
TI - A case of juvenile spongiotic gingivitis.
PMID- 24353816
TI - Phaces syndrome with intraoral and perioral hemangiomas: a different approach
with Diode Laser.
PMID- 24353817
TI - Oral squamous cell carcinoma presenting as a cervical lymphadenopathy.
PMID- 24353818
TI - Focal epithelial hyperplasia (Heck's disease).
PMID- 24353819
TI - Unusual presentation of a solitary plasmocytoma of the jaw: a case report.
PMID- 24353820
TI - A rare case of oral anthracosis resembling an oral leukoplakia.
PMID- 24353821
TI - Lymphoma non-Hodgkin or not: that is the question.
PMID- 24353822
TI - Peripheral gigant cell granuloma (giant cell epulis) associated with metabolic
diseases: case report and literature review.
PMID- 24353823
TI - An unusual case of Oral Lichen Planus.
PMID- 24353824
TI - Sebaceous carcinoma of the lip.
PMID- 24353825
TI - Recrudescent oral HSV infection.
PMID- 24353826
TI - Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced
inflammatory responses through modulation of NF-kappaB/AP-1/PI3K-Akt signaling
cascades in RAW 264.7 cells.
AB - Luteolin is a flavonoid found in abundance in celery, green pepper, and
dandelions. Previous studies have shown that luteolin is an anti-inflammatory and
anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin
and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their
molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)
activated RAW 264.7 cells, luteolin more potently inhibited the production of
nitric oxide (NO) and prostaglandin E2 as well as the expression of their
corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)
than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects
were investigated to determine whether the inflammatory response was related to
the transcription factors, nuclear factor (NF)-kappaB and activator protein (AP)
1, or their upstream signaling molecules, mitogen-activated protein kinases
(MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation
of both transcription factors, NF-kappaB and AP-1, while luteolin-7-O-glucoside
only impeded NF-kappaB activation. However, both flavonoids inhibited Akt
phosphorylation in a dose-dependent manner. Consequently, luteolin more potently
ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be
attributed to the differentially activated NF-kappaB/AP-1/PI3K-Akt pathway in RAW
264.7 cells.
PMID- 24353827
TI - Effects of cranberry powder on biomarkers of oxidative stress and glucose control
in db/db mice.
AB - Increased oxidative stress in obese diabetes may have causal effects on diabetic
complications, including dyslipidemia. Lipopolysccharides (LPS) along with an
atherogenic diet have been found to increase oxidative stress and insulin
resistance. Cranberry has been recognized as having beneficial effects on
diseases related to oxidative stress. Therefore, we employed obese diabetic
animals treated with an atherogenic diet and LPS, with the aim of examining the
effects of cranberry powder (CP) on diabetic related metabolic conditions,
including lipid profiles, serum insulin and glucose, and biomarkers of oxidative
stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups:
normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS,
atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption
of an atherogenic diet resulted in elevation of serum total cholesterol and
atherogenic index (AI) and reduction of high density lipoprotein (HDL)
cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was
close to that of the group with a normal diet, whereas AI was maintained at a
higher level than that of the group with a normal diet. LPS induced elevated
serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean
serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean
activity of liver cytosolic glutathione peroxidase was significantly increased by
LPS injection, however it was reduced back to the value without LPS when the diet
was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean
levels of serum protein carbonyl tended to occur in a dose dependent manner.
Particularly with 10% CP, a reduction of approximately 89% was observed (P >
0.05). Overall results suggest that fortification of the atherogenic diet with CP
may have potential health benefits for obese diabetes with high oxidative stress,
by modulation of physical conditions, including some biomarkers of oxidative
stress.
PMID- 24353828
TI - Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor
(IGF)-1 signaling in mouse skin cancer.
AB - It has been shown that dysregulation of IGF-1 signaling is associated with tumor
incidence and progression, whereas blockade of the signaling can effectively
inhibit carcinogenesis. Although several mechanisms of anticancer activity of
quercetin were proposed, molecular targets of quercetin have not been identified
yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in
BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis.
A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of
skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12
dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage
mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was
significantly inhibited by a quercetin supplementation. Further analysis of the
MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently
suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin
receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the
phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1
stimulated cell proliferation in a dose dependent manner. Taken together, these
data suggest that quercetin has a potent anticancer activity through the
inhibition of IGF-1 signaling.
PMID- 24353829
TI - Chamnamul [Pimpinella brachycarpa (Kom.) Nakai] ameliorates hyperglycemia and
improves antioxidant status in mice fed a high-fat, high-sucrose diet.
AB - Chronic consumption of a high-fat, high-sucrose (HFHS) diet increases insulin
resistance and results in type 2 diabetes mellitus in C57BL/6J mice.
Hyperglycemia in diabetics increases oxidative stress, which is associated with a
high risk of diabetic complications. The purpose of this study was to examine the
hypoglycemic and antioxidant effects of chamnamul [Pimpinella brachycarpa (Kom.)
Nakai] in an animal model of type 2 diabetes. The alpha-glucosidase inhibitory
activity of a 70% ethanol extract of chamnamul was measured in vitro. Five-week
old male C57BL/6J mice were fed a basal or HFHS diet with or without a 70%
ethanol extract of chamnamul at a 0.5% level of the diet for 12 weeks after 1
week of adaptation. After sacrifice, serum glucose, insulin, adiponectin, and
lipid profiles, and lipid peroxidation of the liver were determined. Homeostasis
model assessment for insulin resistance (HOMA-IR) was determined. Chamnamul
extract inhibited alpha-glucosidase by 26.7%, which was 78.3% the strength of
inhibition by acarbose at a concentration of 0.5 mg/mL. Serum glucose, insulin,
and cholesterol levels, as well as HOMA-IR values, were significantly lower in
the chamnamul group than in the HFHS group. Chamnamul extract significantly
decreased the level of thiobarbituric acid reactive substances and increased the
activities of superoxide dismutase, catalase, and glutathione peroxidase in the
liver compared with the HFHS group. These findings suggest that chamnamul may be
useful in prevention of hyperglycemia and reduction of oxidative stress in mice
fed a HFHS diet.
PMID- 24353830
TI - Anti-hyperlipidemic activity of Rhynchosia nulubilis seeds pickled with brown
rice vinegar in mice fed a high-fat diet.
AB - The abnormal content of blood lipids often results in metabolic diseases, such as
hyperlipidemia and obesity. Many agents, including natural sources from
traditional food, have been developed to regulate the blood lipid contents. In
this study, we examined the anti-hyperlipidemic activity of Rhynchosia nulubilis
seeds pickled with brown rice vinegar (RNSpBRV), a Korean traditional pickled
soybean food. Since RNSpBRV is made of R. nulubilis seeds (RNS) soaked in brown
rice vinegar (BRV), we compared the anti-adipogenic activity between RNS, BRV and
solid fraction of RNSpBRV (SF-RNSpBRV), liquid fraction of RNSpBRV (LF-RNSpBRV).
For this, the inhibitory effect of lipid accumulation in 3T3-L1 adipocyte was
checked by adding methanol extracts of mixed RNS and BRV, LF-RNSpBRV, and SF
RNSpBRV. The addition of each methanol extract up to 1 mg/ml showed no
cytotoxicity on 3T3-L1 adipocyte, and approximately 20% of the lipid droplet
formation was suppressed with the methanol extract of BRL or SF-RNSpBRV. The
highest suppression (42.1%) was achieved with LF-RNSpBRV. In addition, mice fed a
high fat diet (HFD) supplemented with 5% RNSpBRV powder led to increased high
density lipoprotein (HDL) cholesterol and lower blood glucose, triglyceride, and
total cholesterol compared to mice fed with a HFD diet only. Interestingly, the
size of the epididymis cells gradually decreased in HFD + 1% RNSpBRV- and HFD +
5% RNSpBRV-fed mice if compared those of HFD-fed mice. Taken together, these
results provide evidence that RNSpBRV has a regulatory role in lipid metabolism
that is related to hyperlipidemia.
PMID- 24353831
TI - Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4
dependent cytokine production in rat model of endotoxic shock.
AB - The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was
investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced
liver failure rats compared with that of acanthoic acid (AA) isolated from AE.
Although D-GalN/LPS (250 mg/kg body weight/10 ug/kg body weight, i.p.) induced
hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA,
equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the
result of a significant decrease in the activity of alanine transaminase.
Concomitantly, both the nitric oxide and IL-6 levels in the plasma were
significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS
control (AE0). This response resulted from the regulation of pro-inflammatory
signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high
degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3
and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and
inflammatory cell infiltrates compared to the AE0. In conclusion, these results
suggest that especially high-dose AE are capable of alleviating D-GalN/LPS
induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR
4-dependent cytokine release. The anti-inflammatory effect of AE could be
contributing to that of AA and AE is better than AA.
PMID- 24353832
TI - Fenugreek seeds reduce aluminum toxicity associated with renal failure in rats.
AB - Despite the reports on safety concerns regarding the relationship between
aluminum salts and neurological and bone disease, many countries continue to use
aluminum as phosphate binders among patients with renal failure. In search for a
diet supplement that could reduce aluminum toxicity related to renal failure, we
carried out this prospective animal study in which the fenugreek seeds were
assessed for their effects on rats nephrotoxicity induced by aluminum chloride
(AlCl3). Oral AlCl3 administration during 5 months (500 mg/kg bw i.g for one
month then 1600 ppm via drinking water) led to plasma biochemical changes, an
inhibition of alkaline phosphatase (ALP), a decrease of total antioxidant status
(TAS), and an induction of lipid peroxidation (LPO) in the blood and brain, in
addition to kidney atrophy and morphological alterations at the level of Bowman's
capsule, the glomerulus and different sorts of tubules, reminiscent of some known
kidney disease. The treatment with the whole fenugreek seed powder (FSP) (5% in
the diet) during the last 2 months showed its effectiveness in restoring normal
plasma values of urea, creatinine, ALP and glucose, as well as re-increasing the
TAS, inhibiting LPO and alleviating histopathological changes in the injured
kidneys. This study highlights the induced nephrotoxicicity, as well as the
related toxicity in the brain and bone, by chronic oral ingestion of the aluminum
salts. However, the maintenance of a diet supplemented with fenugreek seeds could
offer protection for the kidney, bone and brain, at the same time.
PMID- 24353833
TI - Antioxidant effects of fucoxanthin rich powder in rats fed with high fat diet.
AB - The purpose of this study was to determine the antioxidant effect of fucoxanthin.
After rats were fed a normal fat diet (NF), high fat diet (HF), and high fat with
0.2% fucoxanthin diet (HF + Fxn) for 4 weeks, the markers of oxidative stress and
antioxidant capacity like lipid peroxidation, plasma total antioxidant capacity
(TAC), and activities of antioxidant enzymes (catalase, superoxide dismutase
(SOD), and gluthathione peroxidase (GSH-Px)) were determined. mRNA expression of
transcription factor, nuclear erythroid factor like 2 (Nrf2), and its target
genes such as NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase-1 (HO-1)
were also determined. Mean weight gain in the HF + Fxn group was lower, without
statistical significance, and the total food intake in the HF + Fxn group was
lower than that in the HF group (P < 0.05). The activity of GSH-Px (P < 0.05) in
plasma was significantly higher in the HF + Fxn group than those in the HF group
(P < 0.05). In the liver, the activities of catalase (P < 0.05) and GSH-Px (P <
0.05) in the HF + Fxn group were significantly higher than those in the HF group.
Plasma TAC level was significantly higher in the HF + Fxn group than that in the
HF group (P < 0.05). Lipid peroxidation in plasma tended to be lower without
statistical significance. Fucoxanthin supplements were shown to have higher mRNA
expression of Nrf2 and NQO1 than those in the high fat diet only group (P <
0.05). In conclusion, supplementation of fucoxanthin improved the antioxidant
capacity, depleted by high fat diet, by activating the Nrf2 pathway and its
downstream target gene NQO1. Therefore, supplementation of fucoxanthin,
especially for those who consume high fat in their diet, may benefit from reduced
risk of oxidative stress.
PMID- 24353834
TI - Effects of d-alpha-tocopherol supplements on lipid metabolism in a high-fat diet
fed animal model.
AB - High-fat diet up-regulates either insulin resistance or triglycerides, which is
assumed to be related to the expression of peroxisome proliferator-activated
receptor (PPAR)-alpha and PPAR-gamma. The beneficial effects of vitamin E on
insulin resistance are well known; however, it is not clear if vitamin E with a
high-fat diet alters the expression of PPAR-alpha and PPAR-gamma. We investigated
the effects of d-alpha-tocopherol supplementation on insulin sensitivity, blood
lipid profiles, lipid peroxidation, and the expression of PPAR-alpha and PPAR
gamma in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The
animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat,
or a HF diet plus d-alpha-tocopherol (HF-E) for a period of 20 weeks. The results
showed that the HF diet induced insulin resistance and altered the lipid profile,
specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05).
In this animal model, supplementation with d-alpha-tocopherol improved insulin
resistance as well as the serum levels of TG and very-low-density lipoprotein
cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of
malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-alpha
expression and decreasing PPAR-gamma expression. In conclusion, the oral
administration of d-alpha-tocopherol with a high-fat diet had positive effects on
insulin resistance, lipid profiles, and oxidative stress through the expression
of PPAR-alpha and PPAR-gamma in a high-fat diet-fed male mice.
PMID- 24353835
TI - The effects of elimination diet on nutritional status in subjects with atopic
dermatitis.
AB - A food allergy is an adverse health effect arising from a specific immune
response that occurs reproducibly upon exposure to a given food. In those with
food allergies that are thought to cause aggravation of eczema, food avoidance is
important. The objective of this study was to research the nutritional status of
patients with food allergies. A total of 225 subjects diagnosed with atopic
dermatitis underwent a skin prick test as well as measurement of serum
immunoglobulin E. Food challenge tests were conducted using seven food items:
milk, eggs, wheat, soybeans, beef, pork, and chicken. At post-food challenge
visits to the test clinic, participants completed a three-day dietary record,
which included two week days and one weekend day, in order to evaluate energy
intake and diet quality during the challenge. We analyzed nutrient intake based
on differential food allergens. Subjects with a food allergy to milk showed lower
intake of Ca, Zn, and vitamin B2, and subjects with a food allergy to egg showed
lower intake of vitamin A, B1, B2, niacin, and cholesterol. Subjects with a food
allergy to wheat and soybean showed lower intake of Ca, P, Fe, K, Zn, vitamin B2,
vitamin B6, and niacin; and subjects with a food allergy to beef, pork, and
chicken showed lower intake of Fe and higher intake of K, vitamin A, B2. Subjects
with atopic dermatitis were lacking in several nutrients, including vitamin A and
vitamin C. A greater number of food allergies showed an association with a
greater number of nutrient intake deficiencies. Allergen avoidance is the basic
treatment for atopic dermatitis. However, when the allergen is food, excessive
restriction can lead to nutrition deficiency. Findings of this study suggest the
necessity for enhanced nutritional education in order to provide substitute foods
for patients with food allergies who practice food restriction.
PMID- 24353836
TI - Vitamin D status and its association with cardiometabolic risk factors in Korean
adults based on a 2008-2010 Korean National Health and Nutrition Examination
Survey.
AB - Recent studies suggest that vitamin D deficiency and cardiometabolic disorders
are becoming increasingly more prevalent across multiple populations. However,
there is a lack of comprehensive data for Korean adults. We investigated the
vitamin D status, the prevalence of vitamin D deficiency and its association with
metabolic syndrome (MS) risk in Korean adults aged 20 years or older. The study
subjects (n = 18,305) were individuals who participated in the Korean National
Health Examination and Nutrition Survey (KNHANES) in 2008-2010. Vitamin D status
(25-hydroxyvitamin D [25(OH)D]) was categorized as < 20, 21-29, and >= 30 ng/mL,
which are the cut-off points for deficiency, insufficiency and normal limits. A
wide variety of cardiometabolic risk factors were compared according to the
vitamin D status. Vitamin D deficiency was found in 53.9% of men and 70.5% of
women. Mean BMI, systolic BP, HbA1c and low density lipoprotein cholesterol (LDL
C) were highest in the vitamin D deficiency group in both genders. Further, the
MS was most prevalent in the vitamin D deficiency group in both genders (12.3%, P
= 0.002 in men and 9.2%, P < 0.001 in women). Compared to the vitamin D normal
group, the adjusted odds ratio (ORs) (95% confidence interval [95% CI]) for MS in
the vitamin D deficiency group were 1.46 (1.05-2.02) in men and 1.60 (1.21-2.11)
in women, after adjusting for confounding variables. In conclusion, Vitamin D
deficiency is a very common health problem in Korean adults and is independently
associated with the increasing risk of MS.
PMID- 24353837
TI - Estimation of vitamin K intake in Koreans and determination of the primary
vitamin K-containing food sources based on the fifth Korean National Health and
Nutrition Examination Survey (2010-2011).
AB - There is little information on dietary vitamin K intake and nutritional status of
daily requirements of vitamin K in Korea. The objective of this study was to
investigate the vitamin K intake and major food sources of Vitamin K in Koreans.
The survey data from the 2010-2011 Korean National Health and Nutrition
Examination Survey of 7,792 subjects (aged 19-64 years) were examined. Total
vitamin K intake was calculated from 24-hour dietary recall using a vitamin K
food database, Computer Aided Nutritional analysis Program and the United States
Department of Agriculture database. The geometric mean of vitamin K was estimated
as 322.40 +/- 6.33 ug/day for men and 271.20 +/- 4.92 ug/day for women. Daily
vitamin K intake increased significantly with age (p for trend < 0.001). The main
food source of vitamin K was vegetables (72.84%), including cabbage kimchi
(19.26%), spinach (17.38%), sesame leaves (7.11%), radish leaves (6.65%), spring
onions (6.28%), and laver (4.82%), followed by seaweed, seasonings, and fat and
oils. We observed that the vitamin K intake of Koreans was relatively higher than
that reported by other studies in Western countries and differed depending on
age.
PMID- 24353838
TI - The cultivation of wild food and medicinal plants for improving community
livelihood: The case of the Buhozi site, DR Congo.
AB - This study aims to demonstrate the effect of farming technology on introducing
medicinal plants (MP) and wild food plants (WFP) into a traditional agricultural
system within peri-urban zones. Field investigations and semi-structured focus
group interviews conducted in the Buhozi community showed that 27 health and
nutrition problems dominated in the community, and could be treated with 86
domestic plant species. The selected domestic MP and WFP species were collected
in the broad neighboring areas of the Buhozi site, and introduced to the
experimental field of beans and maize crops in Buhozi. Among the 86 plants
introduced, 37 species are confirmed as having both medicinal and nutritional
properties, 47 species with medicinal, and 2 species with nutritional properties.
The field is arranged in a way that living hedges made from Tithonia diversifolia
provide bio-fertilizers to the plants growing along the hedges. The harvest of
farming crops does not disturb the MP or WFP, and vice-versa. After harvesting
the integrated plants, the community could gain about 40 times higher income,
than from harvesting farming crops only. This kind of field may be used
throughout the year, to provide both natural medicines and foods. It may
therefore contribute to increasing small-scale crop producers' livelihood, while
promoting biodiversity conservation. This model needs to be deeply documented,
for further pharmaceutical and nutritional use.
PMID- 24353840
TI - Investigation of efficacy of mitomycin-C, sodium hyaluronate and human amniotic
fluid in preventing epidural fibrosis and adhesion using a rat laminectomy model.
AB - STUDY DESIGN: A retrospective study. PURPOSE: The aim of this study was to
evalute the effects of mitomycin-C, sodium hyaluronate and human amniotic fluid
on preventing spinal epidural fibrosis. OVERVIEW OF LITERATURE: The role of scar
tissue in pain formation is not exactly known, but it is reported that scar
tissue causes adhesions between anatomic structures. Intensive fibrotic tissue
compresses on anatomic structures and increases the sensitivity of the nerve root
for recurrent herniation and lateral spinal stenosis via limiting movements of
the root. Also, neuronal atrophy and axonal degeneration occur under scar tissue.
METHODS: The study design included 4 groups of rats: group 1 was the control
group, groups 2, 3, and 4 receieved antifibrotic agents, mitomycin-C (group 2),
sodium hyaluronate (group 3), and human amniotic fluid (group 4). Midline
incision for all animals were done on L5 for total laminectomy. Four weeks after
the surgery, the rats were sacrificed and specimens were stained with hematoxylin
eosin and photos of the slides were taken for quantitive assesment of the scar
tissue. RESULTS: There was no significant scar tissue in the experimental animals
of groups 2, 3, and 4. It was found that there was no significant difference
between drug groups, but there was a statistically significant difference between
the drug groups and the control group. CONCLUSIONS: This experimental study shows
that implantation of mitomycin-C, sodium hyaluronate and human amniotic fluid
reduces epidural fibrosis and adhesions after spinal laminectomy in rat models.
Further studies in humans are needed to determine the complications of the agents
researched.
PMID- 24353841
TI - Posterior Surgery Alone in the Treatment of Post-traumatic Kyphosis by Posterior
Column Osteotomy, Spondylodesis, Instrumentation, and Vertebroplasty.
AB - STUDY DESIGN: Retrospective study. PURPOSE: To determine if posterior surgery
alone can satisfactorily treat post-traumatic kyphosis (PTK). OVERVIEW OF
LITERATURE: One of the worst complications of vertebral fractures is PTK. The
type of surgery and approach to treat a symptomatic and refractory PTK is a
challenging issue in spinal surgery, and yet, there is no specific treatment
algorithm. METHODS: From August 2003 to September 2010, we collected 26 cases
(male to female ratio, 2.25; mean age, 31.9+/-9.7 years and follow-up period of
42.4+/-8.1 months) with PTK treated by posterior column osteotomy, spondylodesis,
instrumentation and cement vertebroplasty in one stage posterior surgery. PTK
angle, Oswestry Disability Index (ODI), visual analogue scale (VAS), and
subjective satisfaction from surgery were used to determine the results. We used
a student t test for analyzing the data before and after surgery. RESULTS: In our
patients, T11 and L1 had the highest incidence of vertebral fractures. The
results indicated that in PTK, ODI, and VAS were significantly improved this
surgery. Solid fusion occurred in 96.2% of patients with 3.2 degrees +/-2.1
degrees loss of correction. A total of 84.6% of patients have satisfaction level
of excellent and good. CONCLUSIONS: Posterior surgery alone with posterior column
osteotomy, vertebroplasty, posterior spinal fusion and instrumentation can
effectively treat symptomatic PTK.
PMID- 24353842
TI - Magnification error in digital radiographs of the cervical spine against magnetic
resonance imaging measurements.
AB - STUDY DESIGN: Prospective study. PURPOSE: The main purpose of this study was to
clarify the range of magnification errors on digital plain radiographs and to
determine if there is a correlation between the body mass index (BMI) of a
patient and the magnification error. OVERVIEW OF LITERATURE: Most clinicians
currently use digital plain radiography. This new method allows one to access
images and measure lengths and angles more easily than with the past
technologies. In addition, conventional plain radiography has magnification
errors. Although few articles mention magnification errors in regards to digital
radiographs, they are known to have the same errors. METHODS: We used plain
digital radiography and magnetic resonance imaging (MRI) to acquire images of the
cervical spine with the goal of evaluating magnification errors by measuring the
anteroposterior vertebral body lengths of C2 and C5. The magnification error (ME)
was then calculated: ME=(length on radiograph-length on MRI)/length on MRI *100
(%). The correlation coefficient between the magnification error and BMI was
obtained using Pearson's correlation analysis. RESULTS: Average magnification
errors in C2 and C5 were approximately 18.5%+/-5.4% (range, 0%-30%) and 20.7%+/
6.3% (range, 1%-32%). There was no positive correlation between BMI and the
magnification error. CONCLUSIONS: There were magnification errors on the digital
plain radiographs, and they were different in each case. Maximum magnification
error differences were 30% (C2) and 31% (C5). Based on these finding, clinicians
must pay attention to magnification errors when measuring lengths using digital
plain radiography.
PMID- 24353843
TI - Analysis of risk factors for adjacent segment degeneration occurring more than 5
years after fusion with pedicle screw fixation for degenerative lumbar spine.
AB - STUDY DESIGN: A retrospective study. PURPOSE: We investigated the risk factors in
adjacent segment degeneration (ASD) after more than 5 years of follow-up of
lumbar spinal fusion. OVERVIEW OF LITERATURE: There are many concerns regarding
ASD followed by lumbar spinal fusion. However, there is a great deal of dispute
about the risk factors. METHODS: A total of 55 patients who were followed up for
more than 5 years after lumbar fusion were observed. Gender, age, residence,
fusion method, number of fusion segments and radiological measurements were
analyzed. In the radiological measurement, disc height, lumbar lordotic angle
(LLA), fusion segment lordotic angle and fusion segment lordotic angle per level
(FSLA per level) were estimated. In preoperative MRI, Pfirrmann's classification
was used. The clinical result was evaluated by the criteria of Kim and Kim.
Statistical univariate analysis was performed with the chi-square test by using
SPSS ver. 12.0. Multivariate logistic regression analysis was conducted with SAS
ver. 9. RESULTS: There were 21 patients with adjacent segment degeneration.
Further, there was little relationship between ASD and gender, age, residence,
fusion method, number of fusion segments, degree of preoperative adjacent disc
degeneration in MRI, or preoperative and postoperative LLA. However, the
frequency of ASD was significantly low in cases where FSLA per level was >15
degrees (p=0.009). There was no significant relationship between ASD and the
clinical result. CONCLUSIONS: In patients followed up for more than 5 years after
lumbar spinal fusion, the most important factor in the prevention of ASD was the
restoration of FSLA per level to >15 degrees .
PMID- 24353844
TI - Adolescent Idiopathic Scoliosis: A 71 Cases Study Ascertaining that Straightening
Is Possible, and a New Etiological Hypothesis.
AB - STUDY DESIGN: Seventy-one children (23 boys and 48 girls, aged 6 to 18 year-old)
with adolescent idiopathic scoliosis (AIS) between 11 degrees and 62 degrees ,
without braces, have been treated manually, only at the level of the neck.
PURPOSE: To ascertain that non-surgical straightening of AIS is possible (without
brace). OVERVIEW OF LITERATURE: So far no disease modifying treatment for AIS
existed. Braces can only slow down worsening (and this can only be achieved if
they are worn 23 hours a day). Surgery is not without important risks. METHODS:
All patients have been treated exclusively with a manual therapy called Brachy
Myotherapy. This method treats spasmed (contractured) muscles by placing them in
a shortening position according to a specific protocol. RESULTS: An average
straightening of 8 degrees of AIS was observed, with a maximum of 25 degrees .
94% of cases improved, 67 out of 71. The worst prognosis was, the better results.
The more advanced AIS was, the better the results. CONCLUSIONS: A simple and
reliable treatment of AIS is possible. AIS seems to be a compensation mechanism
of the body, with the aim of keeping the ears, and thus the labyrinths, at a
horizontal level for correct equilibrium. When lasting post-traumatic neck muscle
contractures causing a permanent side-bending of the skull have been treated,
this compensation mechanism becomes irrelevant and scoliosis tends to subside.
PMID- 24353845
TI - Cervical foraminal and discal height after dynamic rotational plating in the
cervical discectomy and fusion.
AB - STUDY DESIGN: This is a retrospective study. PURPOSE: To evaluate the effect of
the dynamic rotational plate to the intervertebral foraminal and discal height
after anterior cervical discectomy and fusion. OVERVIEW OF LITERATURE: There is
no report regarding the changes of foraminal and discal height following cervical
dynamic rotational plating. METHODS: We reviewed the outcomes of 30 patients (36
levels), who were followed-up for an average of 15 months (range, 12-57 months)
after undergoing fusions with anterior cervical dynamic rotational plating for
cervical radiculopathy, from March 2005 to February 2009. The changes of
foraminal and intervertebral discal height of the operated levels were observed
on oblique and lateral radiographs obtained at the preoperative, postoperative
and follow-up examinations. RESULTS: The foraminal and discal height increased
sufficiently, immediately following the operation. However, follow-up results
showed gradual decrease in the foraminal and discal height. After 6 months of the
surgery, they showed little difference compared with the preoperative heights.
However, clinically, patients showed improvements in radiating pain during the
follow-up period. CONCLUSIONS: Anterior cervical dynamic rotational plating was
an effective treatment modality for cervical radiculopathy without the
deterioration of the foraminal and intervertebral discal height.
PMID- 24353846
TI - Causes of late revision surgery after bone cement augmentation in osteoporotic
vertebral compression fractures.
AB - STUDY DESIGN: A retrospective study. PURPOSE: To elucidate the causes of late
revision following bone cement augmentation for osteoporotic vertebral
compression fractures (OVCFs). OVERVIEW OF LITERATURE: Percutaneous
vertebroplasty (PVP) or kyphoplasty (KP) is thought to be effective for the
treatment of OVCFs. Many complications related to PVP or KP have been reported.
However, there is a paucity of reports regarding the causes of late revision
surgery after failed PVP or KP. METHODS: Twenty six patients who developed
unremitted back pain and/or progressive neurological deficit after a symptom-free
period since treatment with PVP or KP were enrolled. All patients underwent
cement removal and anterior reconstruction. Among the 26 patients, 22 patients
underwent anterior interbody fusion combined with posterior instrumentation; 4
patients underwent anterior reconstruction only. The causes of revision surgery
were assessed. Clinical results were assessed using a visual analogue scale (VAS)
and Oswestry Disability Index (ODI). The complications were analyzed. RESULTS:
The average time to revision surgery was 18.9+/-14.6 months (range, 3-78 months).
The causes of late revision surgery included 6 late infections, 8 progressive
kyphoses, 10 proximal fractures after instrumented lumbar fusions, and 2 late
neurological involvement. During the mean follow-up period of 13.5+/-7.8 months,
pre-revision mean VAS (8.5+/-0.9) and ODI (81.2+/-12.5) were improved to 4.2+/
1.4 and 54.8+/-17.6, respectively. Five patients (19%) had serious complications
after revision surgery. CONCLUSIONS: This study presents complications of PVP or
KP in the treatment of OVCFs although PVP or KP can be an effective treatment
strategy for OVCF when applied in highly selected patients.
PMID- 24353847
TI - A nation-wide, outpatient-based survey on the pain, disability, and satisfaction
of patients with osteoporotic vertebral compression fractures.
AB - STUDY DESIGN: A nation-wide, outpatient-based, cross-sectional survey with the
use of questionnaires. PURPOSE: To evaluate the pain, disability and satisfaction
of patients with osteoporotic vertebral compression fractures (OVCFs). OVERVIEW
OF LITERATURE: There are no nation-wide data in Korea on the degree of pain,
disability and satisfaction with treatment in patients with OVCFs. METHODS: We
performed a cross-sectional survey of 573 patients with OVCFs. After excluding
incomplete questionnaires (missing more than 30% of the variables), 430 patient
physician-matched data sets were collected for this survey. RESULTS: Patients
with OVCFs were managed with conservative treatment in 63% and with a
vertebroplasty in 37%. The means of the latest visual analogue scale (VAS, 5.2)
and Oswestry Disability Index (ODI, 47.7) scores checked at the time of survey
were significantly higher than those VAS and ODI scores prior to OVCFs (the
prefracture VAS and ODI scores, 3.6 and 26.3, respectively; p<0.001 for both
comparisons). However, the means of the latest VAS and ODI scores were
insignificantly different between the conservative and vertebroplasty groups,
irrespective of the duration from the fractures. Overall, 75% of patients were
satisfied with their clinical outcomes. However, the percentages of patient's
satisfaction were not significantly different between the conservative and
vertebroplasty groups. Eighty-eight percent of patients felt some or marked
deterioration of their general health condition following OVCFs. CONCLUSIONS:
These results indicate that although most patients with OVCFs were satisfied with
their clinical outcomes, their subjective general health conditions, as well as
their pain and disability, did not recover to the prefracture state.
PMID- 24353848
TI - The influence of fat infiltration of back extensor muscles on osteoporotic
vertebral fractures.
AB - STUDY DESIGN: Retrospective study. PURPOSE: To investigate the influence of fat
infiltration at low back extensor muscles on osteoporotic vertebral fracture.
OVERVIEW OF LITERATURE: In persons with stronger back muscles, the risk of
osteoporotic vertebral fractures will likely be lower than in those persons with
weaker back muscles. However, the degree of influence of fat infiltration of the
back extensor muscle on osteoporotic vertebral fracture remains controversial.
METHODS: Two hundred and thirty-seven patients who had undergone lumbar spine
magnetic resonance imaging and bone mineral density (BMD) were enrolled in this
study. The amount of low back extensor muscle was determined using the
pseudocoloring technique on an axial view of the L3 level. The patients were
divided into two groups: osteoporotic vertebral fracture group (group A) and non
fracture group (group B). The amount of low back extensor muscle is compared with
BMD, degenerative change of disc, osteophyte grade of facet joint and promontory
angle to reveal the association between these factors. RESULTS: A negative
correlation is found between age and the amount of low back extensor muscle
(p=0.001). The amount of low back extensor muscle in group A and group B was
60.3%+/-14.5% and 64.2%+/-9.3% respectively, thus showing a significantly smaller
amount of low back extensor muscle in the osteoporotic vertebral fracture group
(p=0.015). CONCLUSIONS: Fat infiltration of low back extensor muscle was
increased in osteoporotic vertebral fracture patients. Therefore, fat
infiltration of low back extensor muscle in an elderly person may be a risk
factor of osteoporotic vertebral fracture.
PMID- 24353849
TI - Discogenic axial back pain: is there a role for nucleoplasty?
AB - STUDY DESIGN: A prospective observational study. PURPOSE: To evaluate the role of
nucleoplasty in the management of discogenic axial back pain; to determine the
influence of concordant pain during provocative discography, annular tear and
loss of disc height on the outcome of nucleoplasty. OVERVIEW OF LITERATURE: The
role of nucleoplasty in the management of radicular leg pain due to disc
herniation is known. However, the data regarding its role in the management of
discogenic axial back pain is scarce. METHODS: A prospective evaluation of 30
patients with discogenic axial back pain undergoing nucleoplasty was performed.
Pain, functional disability and quality of life were assessed using the 100 mm
visual analogue scale (VAS), Oswestry Disability Index (ODI) and Short Form-36
(SF-36), respectively. RESULTS: The mean reduction in VAS was 31.03 and 29.03;
mean reduction in ODI was 24.53 and 20.60; and mean increment in SF-36 was 13.58
and 12.30, at 6 months and at 12 months, respectively. The differences were
statistically significant (p <0.05). Concordant pain during provocative
discography, annular tear and loss of disc height did not affect a clinically
significant improvement in any of the three outcomes (p =0.882, 0.213, and 0.170;
respectively). CONCLUSIONS: Nucleoplasty produced statistically significant
improvements in pain, functional disability and quality of life in patients with
discogenic low back pain at 6 months and at 12 months. Concordant pain during
provocative discography, annular tear and loss of disc height did not influence
any of the outcomes after nucleoplasty in patients with discogenic axial back
pain.
PMID- 24353850
TI - Lumbar disc degenerative disease: disc degeneration symptoms and magnetic
resonance image findings.
AB - STUDY DESIGN: Cross sectional and observational. PURPOSE: To evaluate the
different aspects of lumbar disc degenerative disc disease and relate them with
magnetic resonance image (MRI) findings and symptoms. OVERVIEW OF LITERATURE:
Lumbar disc degenerative disease has now been proven as the most common cause of
low back pain throughout the world. It may present as disc herniation, lumbar
spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms
of lumbar disc degeneration are lower back pain and sciatica which may be
aggravated by standing, walking, bending, straining and coughing. METHODS: This
study was conducted from January 2012 to June 2012. Study was conducted on the
diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based
upon abnormal findings in MRI. Patients with prior back surgery, spine fractures,
sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid
arthritis, active malignancy, and pregnancy were excluded. RESULTS: During the
targeted months, 163 patients of lumbar disc degeneration with mean age of
43.92+/-11.76 years, came into Neurosurgery department. Disc degeneration was
most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc
degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37
(22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated
mostly with lumbar spinal stenosis 7 (18.9%). CONCLUSIONS: Results reported the
frequent occurrence of lumbar disc degenerative disease in advance age. Research
efforts should endeavor to reduce risk factors and improve the quality of life.
PMID- 24353851
TI - Vertebral artery dissection as a cause of cervical radiculopathy.
AB - The acute onset of neck pain and arm weakness is most commonly due to cervical
radiculopathy or inflammatory brachial plexopathy. Rarely, extracranial vertebral
artery dissection may cause radiculopathy in the absence of brainstem ischemia.
We describe a case of vertebral artery dissection presenting as cervical
radiculopathy in a previously healthy 43-year-old woman who presented with
proximal left arm weakness and neck pain aggravated by movement. Cervical
magnetic resonance imaging (MRI) and angiography revealed dissection of the left
vertebral artery with an intramural hematoma compressing the left C5 and C6 nerve
roots. Antiplatelet treatment was commenced, and full power returned after 2
months. Recognition of vertebral artery dissection on cervical MRI as a possible
cause of cervical radiculopathy is important to avoid interventions within the
intervertebral foramen such as surgery or nerve root sleeve injection. Treatment
with antithrombotic agents is important to prevent secondary ischemic events.
PMID- 24353852
TI - Ventral schwannoma of the thoracolumbar spine.
AB - We report two patients with ventral schwannoma in the thoracolumbar region
manifesting as low back pain with or without paraparesis. In both patients
magnetic resonance imaging (MRI) revealed a heterogeneously-enhanced intradural
extramedullary mass in the thoracolumbar region. The tumors were successfully
removed via the posterior approach. Their histology was consistent with
schwannoma. Postoperative MRI showed no evidence of a tumor in either patient.
Spinal schwannomas are common benign intradural extramedullary spinal neoplasms;
most arise from the dorsal- and very few from the anterior roots. A literature
review revealed that ventral schwannomas, including giant tumors as in the one
from case 2 in our study, affect mainly the cervical region, and most are
surgically addressed via the posterior approach. Careful handling of the spinal
cord is mandatory for satisfactory surgical results.
PMID- 24353853
TI - Delayed infrarenal aortic pseudoaneurysm treated by endovascular stent graft in
pyogenic spondylitis.
AB - A 61-year-old male patient with pyogenic spondylodiscitis and epidural and psoas
abscesses underwent posterior decompression, debridement, and instrumented
fusion, followed by anterior debridement and reconstruction. Sudden onset flank
pain was diagnosed 7 weeks postoperatively and was determined to be a
pseudoaneurysm located at the aorta inferior to the renal artery and superior to
the aortic bifurcation area. An endovascular stent graft was applied to
successfully treat the pseudoaneurysm. Postoperative recovery was uneventful and
infection status was stabilized.
PMID- 24353854
TI - Isolated tuberculosis of sacrum with monoparesis: an atypical presentation.
AB - Tuberculosis is a major health problem in developing nations. Spine is the most
commonly affected site for skeletal tuberculosis but involvement of sacrum is
rare. Isolated involvement of sacrum has been reported in literature but none of
the reports has mentioned its clinical presentation as monoparesis. Our case
presented with symptoms of sensory and motor deficit in right lower limb. The
magnetic resonance imaging spine and non contrast computerized tomogram revealed
a sacral lesion but were inconclusive of diagnosis. Histological examination
after computed tomography guided biopsy revealed the condition as tuberculosis.
Anti tubercular treatment was started after confirmation of diagnosis and
continued for 18 months. Erythrocyte sedimentation rate and C-reactive protein
drooped to normal range and patient was symptom free at two-year follow up. This
case report intends to emphasize that sacral tuberculosis, being itself a rare
condition, may present atypically as monoparesis.
PMID- 24353855
TI - Arachnoiditis following caudal epidural injections for the lumbo-sacral radicular
pain.
AB - Caudal epidural steroid injection is a very common intervention in treatment of
low back pain and sciatica symptoms. Although extensively used, it is not devoid
of complications. A few reports of chemical and infective arachnoiditis exist
following lumbar epidural anaesthesia, but none following a caudal epidural
steroid injection.We report a case of arachnoiditis following caudal epidural
steroid injections for lumbar radiculopathy. The patient presented with
contralateral sciatica, worsening low back pain and urinary retention few days
following the injection, followed by worsening motor functions in L4/L5/S1
myotomes with resultant dense foot drop. Gadolinium-enhanced magnetic resonance
imaging suggested infective arachnoiditis with diffuse enhancement and clumping
of the nerve roots within the lumbar and sacral thecal sac. As the number of
injections in the management of back pain and lumbo-sacral radicular pain is
increasing annually, it is imperative to have a thorough understanding of this
potentially dangerous complication and educate the patients appropriately.
PMID- 24353856
TI - Concept of gunshot wound spine.
AB - Gunshot wound (GSW) to the spine which was earlier common in the military
population is now being increasingly noted in civilians due to easy availability
of firearms of low velocity either licensed or illegal combined with an increased
rate of violence in the society. Contributing to 13% to 17% of all spinal
injuries, the management of complex injury to the spine produced by a GSW remains
controversial. Surgery for spinal cord injuries resulting from low velocity GSWs
is reserved for patients with progressive neurologic deterioration, persistent
cerebrospinal fluid fistulae, and sometimes for incomplete spinal cord injuries.
Surgery may also be indicated to relieve active neural compression from a bullet,
bone, intervertebral disk, or a hematoma within the spinal canal. Spinal
instability rarely results from a civilian GSW. Cauda equina injuries from low
velocity GSWs have a better overall outcome after surgery. In general, the
decision to perform surgery should be made on consideration of multiple patient
factors that can vary over a period of time. Although there have been plenty of
individual case reports regarding GSW to the spine, a thorough review of unique
mechanical and biological factors that affect the final outcome has been lacking.
We review the key concepts of pathogenesis and management of GSW to the spine and
propose an algorithm to guide decision making in such cases.
PMID- 24353857
TI - Decreased Expression of TLR-9 and Cytokines in the Presence of Bacteria in
Patients with Otitis Media with Effusion.
AB - OBJECTIVES: Toll-like receptor (TLR)-9 recognizes unmethylated cytidine-phosphate
guanosine (CpG) motifs in bacteria. Therefore, the expression of TLR-9 may differ
according to the results of bacterial culture, and thus a change in
proinflammatory cytokine induction can also be expected. The authors aimed to
assess the differences and relationships between the expression of TLR-9,
cytokines, and nitric oxide synthase (NOS) in otitis media with effusion (OME)
based on bacterial culture results. METHODS: Sixty-eight patients with OME were
divided into culture-positive and culture-negative groups based on middle ear
culture results. mRNA expression of TLR-9, NOS, and cytokines was measured and
analyzed. RESULTS: Bacteria were detected in 38.2% of patients, and the
distribution was as follows: coagulase negative Staphylococcus (10.3%),
Staphylococcus aureus (8.8%), Streptococcus pneumonia (5.9%), and Bacillus spp.
and Haemophilus influenza combined (2.9%). There were no significant differences
in epidemiologic characteristics according to the culture results. Down
regulation of TLR-9 was observed in the culture-positive group (P=0.019).
Cytokines including interleukin (IL)-12 (r=-0.582), tumor necrosis factor (TNF)
alpha (r=-0.569), interferon (IFN)-gamma (r=-0.442), IL-6 (r=-0.395) and
inducible NOS (r=-0.256) tended to decrease with the detection of bacteria.
CONCLUSION: The expression of TLR-9 significantly decreased in OME with confirmed
bacterial pathogens. IL-12, TNF-alpha, IFN-beta, IL-6 expression tended to
decrease with the detection of bacteria. The presence of bacterial pathogens in
OME may be related to abnormalities in the innate immune system.
PMID- 24353858
TI - Compound Heterozygosity for Two Novel SLC26A4 Mutations in a Large Iranian
Pedigree with Pendred Syndrome.
AB - OBJECTIVES: The aim of this study was to detect the genetic cause of deafness in
a large Iranian family. Due to the importance of SLC26A4 in causing hearing loss,
information about the gene mutations can be beneficial in molecular detection and
management of deaf patients. METHODS: We investigated the genetic etiology in a
large consanguineous family with 9 deaf patients from Fars province of Iran with
no GJB2 mutations. Initially, linkage analysis was performed by four DFNB4 short
tandem repeat markers. The result showed linkage to DFNB4 locus. Following that,
DNA sequencing of all 21 exons, their adjacent intronic sequences and the
promoter of SLC26A4 was carried out for mutation detection. RESULTS: Two novel
mutations (c.863-864insT and c.881-882delAC) were identified in exon 7 of the
gene, in both homozygous and compound heterozygous state in patients. CONCLUSION:
Our results supported the importance of the SLC26A4 mutations in the etiology of
hearing loss among the Iranian patients and therefore its mutation screening
should be considered after GJB2 in the molecular diagnostics of hearing loss,
especially when enlarged vestibular aqueduct or goiter is detected.
PMID- 24353859
TI - Capacity of rectified vestibular evoked myogenic potential in correcting
asymmetric muscle contraction power.
AB - OBJECTIVES: Rectified vestibular evoked myogenic potential (rVEMP) is new method
that simultaneously measures the muscle contraction power during VEMP recordings.
Although there are a few studies that have evaluated the effect of the rVEMP,
there is no study that has evaluated the capacity of rVEMP during asymmetrical
muscle contraction. METHODS: Thirty VEMP measurements were performed among 20
normal subjects (mean age, 28.2+/-2.1 years; male, 16). VEMP was measured in the
supine position. The head was turned to the right side by 0 degrees , 15 degrees
, 30 degrees , and 45 degrees and the VEMPs were recorded in each position. The
interaural amplitude difference (IAD) ratio was calculated by the conventional
non-rectified VEMP (nVEMP) and rVEMP. RESULTS: The nVEMP IAD increased
significantly according to increasing neck rotation. The IAD in rVEMP was almost
similar from 0 degrees to 30 degrees . However, the IAD was significantly larger
than the other positions when the neck was rotated 45 degrees . When IAD during 0
degrees was set as a standard, the IAD of the rVEMP was significantly smaller
that the nVEMP only during the 30 degrees rotaion. CONCLUSION: Rectified VEMP is
capable of correcting asymmetrical muscle contraction power. In contrast, it
cannot correct the asymmetry if muscle contraction power asymmetry is 44.8% or
larger. Also, it is not necessary if muscle contraction power asymmetry is 22.5%
or smaller.
PMID- 24353860
TI - Small-group counseling in a modified tinnitus retraining therapy for chronic
tinnitus.
AB - OBJECTIVES: The authors have treated chronic tinnitus patients using a
combination of a simplified tinnitus retraining therapy (TRT) and medications,
which we called modified TRT. In this clinical setting, we have attempted small
group counseling to find a time-effective equivalent of individual counseling.
The aim of the present study was to evaluate the effectiveness of small-group
counseling by comparing the treatment outcomes between individual and small-group
counseling. METHODS: The patients who had distressing chronic tinnitus with
normal hearing or mild hearing loss were included. The subjects were placed into
the small-group (group 1:4) or the individual (group 1:1) counseling group, and
underwent a modified TRT composed of a single session of directive counseling and
ambient sound stimulation. In addition, alprazolam (0.25 mg) and ginkgo biloba
extract (80 mg) were administered orally to the subjects for 3 months. The 3- and
6- month outcomes were assessed using the follow-up rates and tinnitus severity
scores: awareness, tinnitus handicap inventory (THI), loudness, annoyance, and
effect on life. The treatment responses were classified as improvement, no
changes, and worsening. RESULTS: Of the total 149 patients (77 in group 1:1; 72
in group 1:4), 104 patients completed the protocol at 3 months, and 55 patients
at 6 months. The follow-up rates were similar in both groups. Over the period of
6 months, all scores declined significantly except the loudness score at 3 months
in both groups. Treatment responses showed no between-group differences. The
success rate based on THI was 70% in group 1:1, and 64% in group 1:4 at 6 months.
CONCLUSION: The small-group counseling of our modified TRT was comparable to the
individual counseling for tinnitus relief. We suggest that this protocol can be
implemented effectively in any crowded otolaryngology clinics.
PMID- 24353861
TI - Protective Role of Trimetazidine Against Neomycin-induced Hair Cell Damage in
Zebrafish.
AB - OBJECTIVES: Trimetazidine (TMZ) is known to reduce the generation of oxygen
derived free radicals. The objective of the present study was to evaluate the
effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C:
EGFP). METHODS: Five-day, postfertilization zebrafish larvae were exposed to 125
uM neomycin and one of the following TMZ concentrations for 1 hour: 10 uM, 100
uM, 500 uM, 1,000 uM, 1,500 uM, or 2,000 uM. Hair cells within the neuromasts of
the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were
analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell
survival was calculated as a percentage of hair cells in the control group that
were not exposed to neomycin. Ultrastructural changes were evaluated using
scanning electron microscopy. RESULTS: TMZ protected against neomycin-induced
hair cell loss in the neuromasts (TMZ 1,000 uM, 11.2+/-0.4 cells; 125 uM neomycin
only, 4.2+/-0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl
transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the
ultrastructural analysis, structures of mitochondria and hair cells within the
neuromasts were preserved in zebrafish exposed to 125 uM neomycin and 1,000 uM
TMZ. CONCLUSION: TMZ attenuated neomycin-induced hair cell loss in zebrafish. The
results of this study suggest that neomycin induces apoptosis, and that apoptotic
cell death can be prevented by treatment with tremetazidine.
PMID- 24353863
TI - Learning curve of septoplasty with radiofrequency volume reduction of the
inferior turbinate.
AB - OBJECTIVES: Since few studies on surgical training and learning curves have been
performed, majority of inexperienced surgeons are anxious about performing
operations. We aimed to access the results and learning curve of septoplasty with
radiofrequency volume reduction (RFVR) of the inferior turbinate. METHODS: We
included 270 patients who underwent septoplasty with RFVR of the inferior
turbinate by 6 inexperienced surgeons between January 2009 and July 2011. We
analyzed success score, cases of revision, cases of complication, operation time,
and acoustic rhinometry. RESULTS: Success score was relatively high and every
surgeon had few cases of revision and complication. No significant difference was
found in success score, revision, complication case, or acoustic rhinometry
values between early cases and later cases. Operation time decreased according to
increase in experience. However, there was no significant difference in the
operation time after more than 30 cases. CONCLUSION: We can conclude that 30
cases are needed to develop mature surgical skills for septoplasty with RFVR of
the inferior turbinate and that training surgeons do not need to be anxious about
performing this operation in the unskilled state.
PMID- 24353862
TI - Nasal obstruction and palate-tongue position on sleep-disordered breathing.
AB - OBJECTIVES: We wanted to evaluate whether the presence of nasal obstruction makes
a change on the association between the modified Mallampati score and the
severity of sleep-disordered breathing (SDB) and the sleep quality. METHODS:
Polysomnography (PSG), the modified Mallampati score (MMS), the body-mass index,
and a questionnaire about nasal obstruction were acquired from 275 suspected SDB
patients. The subjects were divided into two groups according to the presence of
nasal obstruction. The clinical differences between the two groups were evaluated
and the associations between the MMS and PSG variables in each group were also
assessed. RESULTS: Significant correlations were found between the MMS and many
PSG variables, including the apnea-hypopnea index, the arousal index and the
proportion of deep sleep, for the patients with nasal obstruction, although this
was not valid for the total patients or the patients without nasal obstruction.
CONCLUSION: The severity of SDB and the quality of sleep are well correlated with
the MMS, and especially for the patients with nasal obstruction. The MMS can give
more valuable information about the severity of SDB when combined with simple
questions about nasal obstruction.
PMID- 24353864
TI - Effect of Epigallocatechin-3-Gallate on PMA-Induced MUC5B Expression in Human
Airway Epithelial Cells.
AB - OBJECTIVES: Among the inflammatory mediators, phorbol 12-myristate 13-acetate
(PMA) is associated with the regulation of MUC5B expression in the airway
epithelial cells. Epigallocatechin-3-gallate (EGCG) is the major component of
green tea extract. The biological activity of EGCG includes reduction of
cholesterol and antioxidant activity, as well as anti-inflammatory effect.
However, the precise action mechanism of anti-inflammatory effect of EGCG in the
airway epithelial cells has not been fully defined. This study investigates the
effect and the brief signaling pathway of EGCG on PMA-induced MUC5B expression in
the airway epithelial cells. METHODS: In NCI-H292 airway epithelial cells, the
effect and signaling pathway of EGCG on MUC5B expression were investigated using
real-time polymerase chain reaction analysis, enzyme immunoassay,
immunohistochemical analysis, gelatin zymography assay, and immunoblot analysis.
RESULTS: In NCI-H292 airway epithelial cells, PMA induced MUC5B expression,
phosphorylation of p38 mitogen-activated protein kinase (MAPK), and matrix
metalloproteinase-9 (MMP-9) expression and protein activity. EGCG significantly
decreased PMA-induced MUC5B expression, phosphorylation of p38 MAPK, and MMP-9
expression and protein activity. SB203580 (p38 MAPK inhibitor) significantly
decreased PMA-induced MMP-9 expression. In addition, SB203580 and MMP-9 I (MMP-9
inhibitor) significantly decreased PMA-induced MUC5B expression. CONCLUSION:
These results suggest that EGCG down-regulates PMA-induced MUC5B expression
through the p38 MAPK dependent MMP-9 signaling pathway in human airway epithelial
cells.
PMID- 24353865
TI - Relationships between Tumor Volume and Lymphatic Metastasis and Prognosis in
Early Oral Tongue Cancer.
AB - OBJECTIVES: Although T stage is an important prognostic tool for oral tongue
cancer, it fails to define the depth of invasion and true three-dimensional
volume of primary tumors. The purpose of this paper is to determine the relations
between tumor volume and lymph node metastasis and survival in early oral tongue
cancer. METHODS: Forty-seven patients with T1-2 tongue cancer were included.
Tumor volumes were measured by the computerized segmentation of T2-weighted
magnetic resonance imaging. RESULTS: The overall average tumor volume was 27.7
cm(3) (range, 1.4 to 60.1 cm(3)). A significant positive correlation was found
between tumor volume and pathological T stage, depth of invasion, and cervical
lymph node metastasis (P<0.001, P<0.001, and P=0.002, respectively). When the
tumor volume exceeded 20 cm(3), the cervical metastasis rate increased to 69.2%.
The overall 5-year disease specific survival rate was 80%. There was a
statistically significant association between large tumor volume (>=20 cm(3)) and
the 5-year disease-specific survival (P=0.046). CONCLUSION: Tumor volume larger
than 20 cm(3) was associated with greater risk cervical lymph node metastasis and
poor 5-year disease-specific survival rate in early oral tongue cancer patients.
PMID- 24353866
TI - Comparisons of Three Indicators for Frey's Syndrome: Subjective Symptoms, Minor's
Starch Iodine Test, and Infrared Thermography.
AB - OBJECTIVES: To correlate Frey's syndrome with subjective symptoms, Minor's starch
iodine test results, and infrared thermography measurements, and to discuss the
utility of thermography as a quantitative diagnostic method. METHODS: This study
included 59 patients who underwent unilateral parotidectomy. A subjective
clinical questionnaire and an objective Minor's starch iodine test were performed
to evaluate the incidence of Frey's syndrome. Infrared thermography was
performed, and the subjects were divided into seven groups according to the
temperature differences between operated and unoperated sites. The thermal
differences were correlated with the results from Minor's starch iodine test and
the subjective symptoms questionnaire. RESULTS: Of the 59 patients, 20 patients
(33.9%) reported subjective symptoms after eating; 30 patients (50.8%) tested
positive for Minor's starch iodine test, 19 patients (63.3%) of which reported
subjective symptoms. Of the 29 patients who were negative for the iodine test, 2
patients (6.9%) reported subjective symptoms. Thus, subjective symptoms were well
correlated with Minor's starch iodine test (r=0.589, P<0.001). As the thermal
differences with infrared thermography increased, the number of patients with
subjective symptoms increased (chi(2)=22.5, P<0.001). Using infrared
thermography, the mean temperature difference in the positive group for the
iodine test was 0.82C+/-0.26C, and that in the negative group was 0.10C+/-0.47C.
With increased thermal differences, more patients showed positivity in the iodine
test (chi(2)=29.9, P<0.001). CONCLUSION: Subjective symptoms, Minor's starch
iodine test, and infrared thermography are well correlated with one another.
Quantitative thermography provides clues for the wide variation in the incidence
of Frey's syndrome, and could be a useful method for diagnosing and studying
Frey's syndrome.
PMID- 24353867
TI - Leiomyosarcoma of the middle ear and temporal bone.
AB - Leiomyosarcoma is a malignant tumor of smooth muscle cells that is exceedingly
rare in the middle ear and temporal bone. Wide surgical resection is treatment of
choice and adjuvant treatment has not proven to be of benefit. This is a report
on a patient with otorrhea and rapidly growing mass on postauricualr area. A
tumor that was mainly located in the middle ear and temporal bone was surgically
removed and proved to be a leiomyosarcoma. The optimal surgical technique and
other treatment strategy are discussed.
PMID- 24353868
TI - Epileptic nystagmus and vertigo associated with bilateral temporal and frontal
lobe epilepsy.
AB - Epileptic nystagmus is defined as a quick, repetitive jerky movement of the
eyeball associated with seizure activity. In cases of epileptic nystagmus
associated with ictal discharge from multiple brain areas, localization of the
exact epileptogenic zone could be extremely difficult. In a nine-year-old patient
with epileptic nystagmus and vertigo associated with bilateral temporal and
frontal lobe epilepsy, we could infer the epileptic focus by interpreting the
patient's clinical picture, characteristics of nystagmus, and findings of
electroencephalography.
PMID- 24353869
TI - Exclusively endoscopic resection of nasopharyngeal adenocarcinoma.
AB - We reported two patients with nasopharyngeal adenocarcinoma resected by using the
exclusively endoscopic approach. Case reports and a review of the world
literature concerning nasopharyngeal adenocarcinoma. The tumors were resected
successfully via the exclusively endoscopic approach and no conversions to the
conventional approach were necessary. The two patients were followed up for 26
and 18 months respectively, and no recurrence was noted without postoperative
chemotherapy or radiotherapy. To the best of our knowledge, this is the first
report of endoscopic resection of nasopharyngeal adenocarcinoma. Our experience
revealed that not only for the early recurrent nasopharyngeal carcinoma, the
exclusively endoscopic nasopharyngectomy can be expanded for the resection of
selected nasopharyngeal adenocarcinoma.
PMID- 24353870
TI - Primary extracranial meningioma presenting as a cheek mass.
AB - Meningioma is well known as common disease of the central nervous system, whereas
primary extracranial meningioma is rare, representing 1% to 2% of all
meningiomas. We have experienced a case of primary extracranial meningioma
presenting as a right cheek mass. The tumor was completely excised via a right
lateral rhinotomy incision. Histopathologic examination confirmed the diagnosis
of primary extracranial meningioma.
PMID- 24353871
TI - Gossypiboma of the neck mimicking an isolated neck recurrence.
AB - A gossypiboma (also called textiloma or retained surgical sponge) of the neck is
rarely reported compared to intraabdominal or intrathoracic gossypibomas and also
can be misdiagnosed as metastatic lymph nodes. A patient was referred to our
clinic for a supraclavicular neck mass 6 months after thyroidectomy and neck
dissection for papillary thyroid carcinoma in another hospital. It was initially
considered an isolated neck recurrence, but it was finally diagnosed as
gossypiboma by a pathological examination of the surgically-excised specimen.
Characteristic findings of computed tomography or positron emission
tomography/computed tomography might be helpful to differentiate the gossypiboma
from malignant neck mass or other inflammatory conditions. It is essential for
clinicians to be aware of this disease entity in differential diagnosis of neck
recurrence because a gossypiboma in the neck can be misinterpreted as a
malignancy to induce unwarranted radical surgery.
PMID- 24353872
TI - The relationship of maxillary canines to the facial anatomical landmarks in a
group of Thai people.
AB - PURPOSE: The objective was to evaluate canine positions, intercanine tip width
(ICTW) and width of distal surface of canine (WDC), related to facial landmarks
including interalar width (IAW), intercommissural width (ICoW), and distance
between left and right projection lines drawn from inner canthus of eyes to alae
of the nose (DPICa) in a group of Thai. MATERIALS AND METHODS: One hundred Thai
subjects aged 18-35 years were selected. IAW and ICoW were measured on subject's
face using digital vernier caliper. Irreversible hydrocolloid impression of the
upper arch was taken, and a cast was poured with dental stone. Silicone
impression material was used to take imprint of the incisal edge of upper six
anterior teeth. DPICa was obtained from the subject's face using custom-made
measuring equipment and marked on the silicone incisal imprint. The marks were
then transferred from the imprint to the stone cast and measured with digital
caliper. The ICTW and WDC were also measured on the stone cast. Pearson's
correlation was used to determine the correlation. RESULTS: The results revealed
that the correlation between ICTW-ICoW was 0.429 and ICTW-DPICa was 0.573. The
correlation between WDC-ICoW was 0.426 and WDC-DPICa was 0.547. However, IAW did
not show any correlation with ICTW or WDC (P>.05). CONCLUSION: The correlation
between canine position and facial landmarks was found. ICTW and WDC had
relationship with ICoW and DPICa. DPICa showed stronger correlation with the
position of maxillary canine than that of ICoW.
PMID- 24353873
TI - Effect of alendronate on bone remodeling around implant in the rat.
AB - PURPOSE: The purpose of this study was to evaluate the effect of alendronates on
bone remodeling around titanium implant in the maxilla of rats. MATERIALS AND
METHODS: The maxillary first molars were extracted and customized-titanium
implants were placed immediately in thirty male Sprague-Dawley rats. The rats
were divided into experimental (bisphosphonate) group and control group. At 4
weeks after implantation, the rats in the bisphosphonate group were
subcutaneously injected with alendronate three times a week for 6 weeks where as
the rats in control group were injected with saline. The rats were sacrificed at
1, 2, 3, 4, or 6 weeks after starting of injection and maxillary bones were
collected subsequently. Alveolar bone remodeling around the implants were
evaluated by radiographic and histologic analysis. Microarray analysis and
immunohistomorphologic analysis were also performed on one rat, sacrificed at 6
weeks after starting of injection, from each group. Statistical analysis was
performed using repeated measures analysis of variance and independent t test at
a significance level of 5%. RESULTS: There was no statistically significant
difference in the bone area (%) around implant between the bisphosphonate group
and the control group. However, the amount of empty lacuna was significantly
increased in the bisphosphonate group, especially in the rats sacrificed at 4
weeks after starting of injection compared to that of the corresponding control
group. The bisphosphonate group showed the same level of TRAP positive cell
count, osteocalcin and angiopoietin 1 as the control group. CONCLUSION:
Alendronate may not decrease the amount of osteoclast. However, the significantly
increased amount of empty lacuna in the bisphosphonate group may explain the
suppression of bone remodeling in the bisphosphonate group.
PMID- 24353874
TI - The effect of alumina and aluminium nitride coating by reactive magnetron
sputtering on the resin bond strength to zirconia core.
AB - PURPOSE: Although several surface treatments have been recently investigated both
under in vitro and in vivo conditions, controversy still exists regarding the
selection of the most appropriate zirconia surface pre-treatment. The purpose of
this study was to evaluate the effect of alumina (Al) and aluminium nitride (AlN)
coating on the shear bond strength of adhesive resin cement to zirconia core.
MATERIALS AND METHODS: Fifty zirconia core discs were divided into 5 groups; air
particle abrasion with 50 um aluminum oxide particles (Al2O3), polishing + Al
coating, polishing + AlN coating, air particle abrasion with 50 um Al2O3 + Al
coating and air particle abrasion with 50 um Al2O3 + AlN coating. Composite resin
discs were cemented to each of specimens. Shear bond strength (MPa) was measured
using a universal testing machine. The effects of the surface preparations on
each specimen were examined with scanning electron microscope (SEM). Data were
statistically analyzed by one-way ANOVA (alpha=.05). RESULTS: The highest bond
strengths were obtained by air abrasion with 50 um Al2O3, the lowest bond
strengths were obtained in polishing + Al coating group (P<.05). CONCLUSION: Al
and AlN coatings using the reactive magnetron sputtering technique were found to
be ineffective to increase the bond strength of adhesive resin cement to zirconia
core.
PMID- 24353875
TI - Analysis of the characteristics of mouthguards that affect isokinetic muscular
ability and anaerobic power.
AB - PURPOSE: The purpose of this study was to estimate the effects of occlusal
stability to identify action mechanisms of mouthguards, known to have a
modulatory effect on limb muscle function. MATERIALS AND METHODS: This study
included 20 male subjects to perform the isokinetic muscle tests and the Wingate
anaerobic power test on both knee joints under five closed-mouth conditions:
without or with 4 types of mouthguards with thickness of 2 mm based on premolar
area: (1) full-coverage, (2) anterior partial-coverage, (3) right posterior
partial-coverage, and (4) left posterior partial-coverage. The obtained results
were subjected to One-way ANOVA with repeated measures, followed by post hoc test
of the contrast method (alpha=.05). RESULTS: There was no significant difference
between the closed position with and without a full-coverage mouthguard in all
variables. However, significant differences were observed between with and
without a partial-coverage mouthguard in muscular endurance during extension of
the left knee, muscular power and endurance during flexion of the right knee.
Additionally, significant differences were found between occlusal states with
full- and partial-coverage mouthguards in muscular power and endurance during
extension of the left knee. CONCLUSION: These findings indicate the elevation of
vertical dimension by 2 mm or the inducement of occlusal stability had little
effect on isokinetic muscle strength and anaerobic performance, while uneven
distribution of occlusal force might have some positive effects.
PMID- 24353876
TI - In vitro comparison of two different materials for the repair of urethan
dimethacrylate denture bases.
AB - PURPOSE: The purpose of this in vitro study was to investigate the flexural
properties of a recently introduced urethane dimethacrylate denture base material
(Eclipse) after being repaired with two different materials. MATERIALS AND
METHODS: Two repair groups and a control group consisting of 10 specimens each
were generated. The ES group was repaired with auto-polymerizing polymer. The EE
group was repaired with the Eclipse. The E group was left intact as a control
group. A 3-point bending test device which was set to travel at a crosshead speed
of 5 mm/min was used. Specimens were loaded until fracture occurred and the mean
displacement, maximum load, flexural modulus and flexural strength values and
standard deviations were calculated for each group and the data were
statistically analyzed. The results were assessed at a significance level of
P<.05. RESULTS: The mean "displacement", "maximum load before fracture",
"flexural strength" and "flexural modulus" rates of Group E were statistically
significant higher than those of Groups ES and EE, but no significant difference
(P>.05) was found between the mean values of Group ES and EE. There was a
statistically significant positive relation (P<.01) between the displacement and
maximum load of Group ES (99.5%), Group EE (94.3%) and Group E (84.4%).
CONCLUSION: The more economic and commonly used self-curing acrylic resin can be
recommended as an alternative repair material for Eclipse denture bases.
PMID- 24353877
TI - Effect of magnesium and calcium phosphate coatings on osteoblastic responses to
the titanium surface.
AB - PURPOSE: The aim of this study was to evaluate the surface properties and in
vitro bioactivity to osteoblasts of magnesium and magnesium-hydroxyapatite coated
titanium. MATERIALS AND METHODS: Themagnesium (Mg) and magnesium-hydroxyapatite
(Mg-HA) coatings on titanium (Ti) substrates were prepared by radio frequency
(RF) and direct current (DC) magnetron sputtering.The samples were divided into
non-coated smooth Ti (Ti-S group), Mg coatinggroup (Ti-Mg group), and Mg-HA
coating group (Ti-MgHA group).The surface properties were evaluated using
scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS).
The surface roughness was evaluated by atomic force microscopy (AFM). Cell
adhesion, cell proliferation and alkaline phosphatase (ALP) activity were
evaluated using MC3T3-E1 cells. Reverse transcription polymerase chain reaction
(RT-PCR) analysis was performed. RESULTS: Cross-sectional SEM images showed that
Mg and Mg-HA depositionson titanium substrates were performed successfully. The
surface roughness appeared to be similaramong the three groups. Ti-MgHA and Ti-Mg
group had improved cellular responses with regard to the proliferation, alkaline
phosphatase (ALP) activity, and bone-associated markers, such as bone
sialoprotein (BSP) and osteocalcin (OCN) mRNA compared to those of Ti-S group.
However, the differences between Ti-Mg group and Ti-MgHA group were not
significant, in spite of the tendency of higher proliferation, ALP activity and
BSP expression in Ti-MgHA group. CONCLUSION: Mg and Mg-HAcoatings could stimulate
the differentiation into osteoblastic MC3T3-E1 cells, potentially contributing to
rapid osseointegration.
PMID- 24353878
TI - The impact of frenulum height on strains in maxillary denture bases.
AB - PURPOSE: The midline fracture of maxillary complete dentures is a frequently
encountered complication. The purpose of this study was to assess the effect of
frenulum height on midline strains of maxillary complete dentures. MATERIALS AND
METHODS: A removable maxillary complete denture was fabricated and duplicated
seven times. Four different labial frenulum heights were tested for stresses
occurring on the palatal cameo surface. The strains were measured with strain
gauges placed on 5 different locations and the stresses were calculated. To mimic
occlusal forces bilaterally 100 N of load was applied from the premolar and molar
region. RESULTS: A statistically significant association between the height of
the labial frenulum and the calculated stresses and strains was shown (P<.05)
predominantly on the midline and especially on the incisive papilla. The results
showed that stress on the anterior midline of the maxillary complete denture
increases with a higher labial frenulum. CONCLUSION: Within the limitations of
this in vitro study, it can be concluded that the stress on the anterior midline
of the maxillary complete denture increases with a higher labial frenulum.
Surgical or mechanical precautions should be taken to prevent short-term failure
of maxillary complete dentures due to stress concentration and low cycle fatigue
tendency at the labial frenulum region.
PMID- 24353879
TI - Gene expression of MC3T3-E1 osteoblastic cells on titanium and zirconia surface.
AB - PURPOSE: This study was performed to define attachment and growth behavior of
osteoblast-like cells and evaluate the gene expression on zirconia compared to
titanium. MATERIALS AND METHODS: MC3T3-E1 cells were cultured on (1) titanium and
(2) zirconia discs. The tetrazolium-based colorimetric assay (MTT test) was used
for examining the attachment of cells. Cellular morphology was examined by
scanning electron microscopy (SEM) and alkaline phosphatase (ALP) activity was
measured to evaluate the cell differentiation rate. Mann-Whitney test was used to
assess the significance level of the differences between the experimental groups.
cDNA microarray was used for comparing the 20215 gene expressions on titanium and
zirconia. RESULTS: From the MTT assay, there was no significant difference
between titanium and zirconia (P>.05). From the SEM image, after 4 hours of
culture, cells on both discs were triangular or elongated in shape with formation
of filopodia. After 24 hours of culture, cells on both discs were more flattened
and well spread compared to 4 hours of culture. From the ALP activity assay, the
optical density of E1 cells on titanium was slightly higher than that of E1 cells
on zirconia but there was no significant difference (P>.05). Most of the genes
related to cell adhesion showed similar expression level between titanium and
zirconia. CONCLUSION: Zirconia showed comparable biological responses of
osteoblast-like cells to titanium for a short time during cell culture period.
Most of the genes related to cell adhesion and signal showed similar expression
level between titanium and zirconia.
PMID- 24353880
TI - Tensile bond strength of four denture resins to porcelain teeth with different
surface treatment.
AB - PURPOSE: This study evaluated the bond strength between porcelain denture teeth
(Bioblend 43D) and four different polymerized denture resins (Lucitone 199,
Palapress, Acron MC, Triad) with and without a bonding agent and after four
different types of surface treatment (polished, HF etched, sandblasted, air
abraded). MATERIALS AND METHODS: Central incisor porcelain denture teeth were
divided into 32 groups of 5 each. Tensile bond strength (MPa) was determined
using a testing machine at crosshead speed of 0.5 mm/min. Mean and standard
deviation are listed. Data were analyzed by two-way ANOVA. Means were compared by
Tukey-Kramer intervals at 0.05 significance level. RESULTS: All surface treatment
increased bond strength compared to polished surface and the highest bond
strength was found with Palapress resin with etched porcelain surface (8.1 MPa).
Bonding agent improved the bond strength of all denture resins to porcelain
teeth. Superior bonding was found with Palapress and air-abraded porcelain (39
MPa). CONCLUSION: Resins with different curing methods affect the bond strength
of porcelain teeth to denture bases. Superior bonding was found with auto
polymerized resin (Palapress). Application of ceramic primer and bonding agent to
porcelain teeth with and without surface treatment will improve the bond strength
of all denture resins to porcelain teeth.
PMID- 24353881
TI - In vitro evaluation of resonance frequency analysis values to different implant
contact ratio and stiffness of surrounding material.
AB - PURPOSE: The present study was aimed to evaluate the influence of implant contact
ratio and stiffness of implant-surrounding materials on the resonance frequency
analysis (RFA) values. MATERIALS AND METHODS: Seventy resin blocks that had the
different amounts (100, 50, 30, 15%) of resin-implant contact (RIC) were
fabricated. Ten silicone putty blocks with 100% silicone-implant contact were
also made. The implants with O5.0 mm * 13.0 mm were placed on eighty specimen
blocks. The RFA value was measured on the transducer that was connected to each
implant by Osstell Mentor. Kruskal-Wallis and Scheffe's tests (alpha=.05) were
done for statistical analysis. RESULTS: The control resin group with 100% RIC had
the highest RFA value of 83.9, which was significantly different only from the
resin group with 15% RIC among the resin groups. The silicone putty group with
100% contact had the lowest RFA value of 36.6 and showed statistically
significant differences from the resin groups. CONCLUSION: Within the limitations
of this in vitro study, there was no significant difference in the RFA values
among the resin groups with different RIC's except when the RIC difference was
more than 85%. A significant increase in the RFA value was observed related to
the increase in stiffness of material around implant.
PMID- 24353882
TI - Stress distribution of oval and circular fiber posts in amandibular premolar: a
three-dimensional finite element analysis.
AB - PURPOSE: The aim of the present study was to evaluate the effects of posts with
different morphologies on stress distribution in an endodontically treated
mandibular premolar by using finite element models (FEMs). MATERIALS AND METHODS:
A mandibular premolar was modeled using the ANSYS software program. Two models
were created to represent circular and oval fiber posts in this tooth model. An
oblique force of 300 N was applied at an angle of 45 degrees to the occlusal
plane and oriented toward the buccal side. von Mises stress was measured in three
regions each for oval and circular fiber posts. RESULTS: FEM analysis showed that
the von Mises stress of the circular fiber post (426.81 MPa) was greater than
that of the oval fiber post (346.34 MPa). The maximum distribution of von Mises
stress was in the luting agent in both groups. Additionally, von Mises stresses
accumulated in the coronal third of root dentin, close to the post space in both
groups. CONCLUSION: Oval fiber posts are preferable to circular fiber posts in
oval-shaped canals given the stress distribution at the post-dentin interface.
PMID- 24353883
TI - An assessment of template-guided implant surgery in terms of accuracy and related
factors.
AB - PURPOSE: Template-guided implant therapy has developed hand-in-hand with computed
tomography (CT) to improve the accuracy of implant surgery and future
prosthodontic treatment. In our present study, the accuracy and causative factors
for computer-assisted implant surgery were assessed to further validate the
stable clinical application of this technique. MATERIALS AND METHODS: A total of
102 implants in 48 patients were included in this study. Implant surgery was
performed with a stereolithographic template. Pre- and post-operative CTs were
used to compare the planned and placed implants. Accuracy and related factors
were statistically analyzed with the Spearman correlation method and the linear
mixed model. Differences were considered to be statistically significant at
P<=.05. RESULTS: The mean errors of computer-assisted implant surgery were 1.09
mm at the coronal center, 1.56 mm at the apical center, and the axis deviation
was 3.80 degrees . The coronal and apical errors of the implants were found to be
strongly correlated. The errors developed at the coronal center were magnified at
the apical center by the fixture length. The case of anterior edentulous area and
longer fixtures affected the accuracy of the implant template. CONCLUSION: The
control of errors at the coronal center and stabilization of the anterior part of
the template are needed for safe implant surgery and future prosthodontic
treatment.
PMID- 24353884
TI - The effect of coloring liquids on the translucency of zirconia framework.
AB - PURPOSE: Translucency of all-ceramic restorations is an important factor which
affects the final appearance and esthetic outcome of the restoration. The aim of
this study was to evaluate the effect of the shade of coloring liquid on the
translucency of zirconia framework. MATERIALS AND METHODS: Thirty zirconium oxide
core plate (15 * 12 * 0.5 mm) were divided into 6 groups of 5 plates each. Each
group was classified according to the shade of coloring liquid based on Vita
Classic Scale (A2, A3, B1, C2, and D2), and each sample was immersed in coloring
liquid for 3 seconds as recommended by the manufacturer, except for the control
group. Contrast ratio, as a translucency parameter, was calculated using a
spectrophotometer and the data were analyzed with oneway analysis of variance
(ANOVA) and Tukey's honestly significant differences (HSD) tests (alpha=.05).
RESULTS: Significant differences in translucency among the control and test
groups, and the B1 shaded group and other shades was observed. There were no
significant differences among A2, A3, C2, and D2 shaded groups. CONCLUSION: The
translucency of the zirconium oxide cores was affected by the coloring procedure
and significant differences in the translucency measurements were identified
between specific shades.
PMID- 24353885
TI - White light scanner-based repeatability of 3-dimensional digitizing of silicon
rubber abutment teeth impressions.
AB - PURPOSE: The aim of this study was to evaluate the repeatability of the
digitizing of silicon rubber impressions of abutment teeth by using a white light
scanner and compare differences in repeatability between different abutment teeth
types. MATERIALS AND METHODS: Silicon rubber impressions of a canine, premolar,
and molar tooth were each digitized 8 times using a white light scanner, and 3D
surface models were created using the point clouds. The size of any discrepancy
between each model and the corresponding reference tooth were measured, and the
distribution of these values was analyzed by an inspection software (PowerInspect
2012, Delcamplc., Birmingham, UK). Absolute values of discrepancies were analyzed
by the Kruskal-Wallis test and multiple comparisons (alpha=.05). RESULTS: The
discrepancy between the impressions for the canine, premolar, and molar teeth
were 6.3 um (95% confidence interval [CI], 5.4-7.2), 6.4 um (95% CI, 5.3-7.6),
and 8.9 um (95% CI, 8.2-9.5), respectively. The discrepancy of the molar tooth
impression was significantly higher than that of other tooth types. The largest
variation (as mean [SD]) in discrepancies was seen in the premolar tooth
impression scans: 26.7 um (95% CI, 19.7-33.8); followed by canine and molar teeth
impressions, 16.3 um (95% CI, 15.3-17.3), and 14.0 um (95% CI, 12.3-15.7),
respectively. CONCLUSION: The repeatability of the digitizing abutment teeth's
silicon rubber impressions by using a white light scanner was improved compared
to that with a laser scanner, showing only a low mean discrepancy between 6.3 um
and 8.9 um, which was in an clinically acceptable range. Premolar impression with
a long and narrow shape showed a significantly larger discrepancy than canine and
molar impressions. Further work is needed to increase the digitizing performance
of the white light scanner for deep and slender impressions.
PMID- 24353886
TI - The effect of a diode laser and traditional irrigants on the bond strength of
self-adhesive cement.
AB - PURPOSE: The purpose of this study was to compare the effect of a diode laser and
traditional irrigants on the bond strength of self-adhesive cement. MATERIALS AND
METHODS: Fifty-five incisors extracted due to periodontal problems were used. All
teeth were instrumented using a set of rotary root canal instruments. The post
spaces were enlarged for a No.14 (diameter, 1.4 mm) Snowlight (Abrasive
technology, OH, USA) glass fiber reinforced composite post with matching drill.
The teeth were randomly divided into 5 experimental groups of 11 teeth each. The
post spaces were treated with the followings: Group 1: 5 mL 0.9% physiological
saline; Group 2: 5 mL 5.25% sodium hypochlorite; Group 3: 5 mL 17% ethylene
diamine tetra acetic acid (EDTA), Group 4: 37% orthophosphoric acid and Group 5:
Photodynamic diode laser irradiation for 1 minute after application of light
active dye solution. Snowlight posts were luted with self-adhesive resin cement.
Each root was sectioned perpendicular to its long axis to create 1 mm thick
specimens. The push-out bond strength test method was used to measure bond
strength. One tooth from each group was processed for scanning electron
microscopic analysis. RESULTS: BOND STRENGTH VALUES WERE AS FOLLOW: Group 1 =
4.15 MPa; Group 2 = 3.00 MPa; Group 3 = 4.45 MPa; Group 4 = 6.96 MPa; and Group 5
= 8.93 MPa. These values were analysed using one-way ANOVA and Tukey honestly
significant difference test (P<.05). Significantly higher bond strength values
were obtained with the diode laser and orthophosphoric acid (P<.05). There were
no differences found between the other groups (P>.05). CONCLUSION:
Orthophosphoric acid and EDTA were more effective methods for removing the smear
layer than the diode laser. However, the diode laser and orthophosphoric acid
were more effective at the cement dentin interface than the EDTA, Therefore,
modifying the smear layer may be more effective when a self-adhesive system is
used.
PMID- 24353887
TI - Degree of conversion of two dual-cured resin cements light-irradiated through
zirconia ceramic disks.
AB - PURPOSE: The aim of this Fourier transform infrared (FTIR) spectroscopic study
was to measure the degree of conversion (DC) of dual-cured resin cements light
irradiated through zirconia ceramic disks with different thicknesses using
various light-curing methods. MATERIALS AND METHODS: Zirconia ceramic disks
(KT12) with three different thicknesses (1.0, 2.0, and 4.0 mm) were prepared. The
light transmittance of the disks was measured using ultraviolet visible near
infrared spectroscopy. Four different light-curing protocols were used by
combining two curing light modes (Elipar TriLight (standard mode) and bluephase
G2 (high power mode)) with light-exposure times of 40 and 120 seconds. The DCs of
the two dual-cured resin cements (Duo-Link and Panavia F2.0) light-irradiated
through the disks was analyzed at three time intervals (3, 7, and 10 minutes) by
FTIR spectroscopy. The data was analyzed using repeated measures ANOVA
(alpha=.05).Two-way ANOVA and Tukey post hoc test were used to analyze the 10
minute DC results. RESULTS: The 1.0 mm thick disk exhibited low light
transmittance (<25%), and the transmittance decreased considerably with
increasing disk thickness. All groups exhibited significantly higher 10 minute DC
values than the 3 or 7 minute values (P<.05), but some exceptions were observed
in Duo-Link. Two-way ANOVA revealed that the influence of the zirconia disk
thickness on the 10 minute DC was dependent on the light-curing methods (P<.001).
This finding was still valid even at 4.0 mm thickness, where substantial light
attenuation took place. CONCLUSION: The curing of the dual-cured resin cements
was affected significantly by the light-curing technique, even though the
additional chemical polymerization mechanism worked effectively.
PMID- 24353888
TI - Annealing of Co-Cr dental alloy: effects on nanostructure and Rockwell hardness.
AB - PURPOSE: The aim of the study was to evaluate the effect of annealing on the
nanostructure and hardness of Co-Cr metal ceramic samples that were fabricated
with a direct metal laser sintering (DMLS) technique. MATERIALS AND METHODS: Five
groups of Co-Cr dental alloy samples were manufactured in a rectangular form
measuring 4 * 2 * 2 mm. Samples fabricated by a conventional casting technique
(Group I) and prefabricated milling blanks (Group II) were examined as
conventional technique groups. The DMLS samples were randomly divided into three
groups as not annealed (Group III), annealed in argon atmosphere (Group IV), or
annealed in oxygen atmosphere (Group V). The nanostructure was examined with the
small-angle X-ray scattering method. The Rockwell hardness test was used to
measure the hardness changes in each group, and the means and standard deviations
were statistically analyzed by one-way ANOVA for comparison of continuous
variables and Tukey's HSD test was used for post hoc analysis. P values of <.05
were accepted as statistically significant. RESULTS: The general nanostructures
of the samples were composed of small spherical entities stacked atop one another
in dendritic form. All groups also displayed different hardness values depending
on the manufacturing technique. The annealing procedure and environment directly
affected both the nanostructure and hardness of the Co-Cr alloy. Group III
exhibited a non-homogeneous structure and increased hardness (48.16 +/- 3.02 HRC)
because the annealing process was incomplete and the inner stress was not
relieved. Annealing in argon atmosphere of Group IV not only relieved the inner
stresses but also decreased the hardness (27.40 +/- 3.98 HRC). The results of
fitting function presented that Group IV was the most homogeneous product as the
minimum bilayer thickness was measured (7.11 A). CONCLUSION: After the
manufacturing with DMLS technique, annealing in argon atmosphere is an essential
process for Co-Cr metal ceramic substructures. The dentists should be familiar
with the materials that are used in clinic for prosthodontics treatments.
PMID- 24353889
TI - The effect of additional etching and curing mechanism of composite resin on the
dentin bond strength.
AB - PURPOSE: The aim of this study was to evaluate the effects of additional acid
etching and curing mechanism (light-curing or self-curing) of a composite resin
on the dentin bond strength and compatibility of one-step self-etching adhesives.
MATERIALS AND METHODS: Sixteen human permanent molars were randomly divided into
eight groups according to the adhesives used (All-Bond Universal: ABU, Clearfil
S3 Bond: CS3), additional acid etching (additional acid etching performed: EO, no
additional acid etching performed: EX), and composite resins (Filtek Z-250: Z250,
Clearfil FII New Bond: CFNB). Group 1: ABU-EO-Z250, Group 2: ABU-EO-CFNB, Group
3: ABU-EX-Z250, Group 4: ABU-EX-CFNB, Group 5: CS3-EO-Z250, Group 6: CS3-EO-CFNB,
Group 7: CS3-EX-Z250, Group 8: CS3-EX-CFNB. After bonding procedures, composite
resins were built up on dentin surfaces. After 24-hour water storage, the teeth
were sectioned to make 10 specimens for each group. The microtensile bond
strength test was performed using a microtensile testing machine. The failure
mode of the fractured specimens was examined by means of an optical microscope at
*20 magnification. The data was analyzed using a one-way ANOVA and Scheffe's post
hoc test (alpha=.05). RESULTS: Additional etching groups showed significantly
higher values than the no additional etching group when using All-Bond Universal.
The light-cured composite resin groups showed significantly higher values than
the self-cured composite resin groups in the Clearfil S3 Bond. CONCLUSION: The
additional acid etching is beneficial for the dentin bond strength when using low
acidic one-step self-etch adhesives, and low acidic one-step self-etch adhesives
are compatible with self-cured composite resin. The acidity of the one-step self
etch adhesives is an influencing factor in terms of the dentin bonding strength
and incompatibility with a self-cured composite resin.
PMID- 24353890
TI - Bond strength of veneer ceramic and zirconia cores with different surface
modifications after microwave sintering.
AB - PURPOSE: To evaluate the effects of surface treatments on shear bond strength
(SBS) between microwave and conventionally sintered zirconia core/veneers.
MATERIALS AND METHODS: 96 disc shaped Noritake Alliance zirconia specimens were
fabricated using YenaDent CAM unit and were divided in 2 groups with respect to
microwave or conventional methods (n=48/group). Surface roughness (Ra) evaluation
was made with a profilometer on randomly selected microwave (n=10) and
conventionally sintered (n=10) cores. Specimens were then assessed into 4
subgroups according to surface treatments applied (n=12/group). Groups for
microwave (M) and conventionally (C) sintered core specimens were as follows;
MC,CC: untreated (control group), M1,C1:Al2O3 sandblasting, M2,C2:liner,
M3,C3:Al2O3 sandblasting followed by liner. Veneer ceramic was fired on zirconia
cores and specimens were thermocycled (6000 cycles between 5 degrees -55C). All
specimens were subjected to SBS test using a universal testing machine at 0.5
mm/min, failure were evaluated under an optical microscope. Data were
statistically analyzed using Shapiro Wilk, Levene, Post-hoc Tukey HSD and
Student's t tests, Two-Way-Variance-Analysis and One-Way-Variance-Analysis
(alpha=.05). RESULTS: Conventionally sintered specimens (1.06 +/- 0.32 um) showed
rougher surfaces compared to microwave sintered ones (0.76 +/- 0.32 um)(P=.046),
however, no correlation was found between SBS and surface roughness (r=-0.109,
P=.658). The statistical comparison of the shear bond strengths of C3 and C1
group (P=.015); CC and MC group (P=.004) and C3 and M3 group presented
statistically higher (P=.005) values. While adhesive failure was not seen in any
of the groups, cohesive and combined patterns were seen in all groups.
CONCLUSION: Based on the results of this in-vitro study, Al2O3- sandblasting
followed by liner application on conventionally sintered zirconia cores may be
preferred to enhance bond strength.
PMID- 24353891
TI - Morphometric analysis of maxillary alveolar regions for immediate implantation.
AB - PURPOSE: The purpose of this study was to provide an actual guideline in
determining the shape, diameter, and position of the implant in immediate
implantation by the measurement of the thickness of facial and palatal plate, the
thickness of cortical bone on the facial and palatal plate, the diameter of the
root, and the distance between the roots in the cadavers. MATERIALS AND METHODS:
The horizontal sections of 20 maxillae were measured and analyzed to obtain the
average values. Resin blocks were produced and cut serially at 1 mm intervals
from the cervical line to the root apex. Images of each section were obtained and
the following measurements were performed: The thickness of the facial and
palatal residual bone at each root surface, the thickness of the facial and
palatal cortical bone at the interdental region, the diameter of all roots of
each section on the faciopalatal and mesiodistal diameter, and the interroot
distance. Three specimens with measurements close to the average values were
chosen and 3-dimensional images were reconstructed. RESULTS: The thickness of the
facial and palatal cortical bone at the interdental region in the maxilla, the
buccal cortical bone was thicker in the posterior region compared to the anterior
region. The interroot distance of the alveolar bone thickness between the roots
increased from anterior to posterior region and from coronal to apical in the
maxilla. CONCLUSION: In this study, the limited results of the morphometric
analysis of the alveolar ridge using the sections of maxilla in the cadavers may
offer the useful information when planning and selecting optimal implant for
immediate implantation in the maxilla.
PMID- 24353893
TI - The role of gut microbiota in programming the immune phenotype.
AB - The human fetus lives in a germ-free intrauterine environment and enters the
outside world containing microorganisms from several sources, resulting in gut
colonization. Full-term, vaginally born infants are completely colonized with a
diverse array of bacterial families in clusters (Phyla) and species (>1000) by
the first year of life. Colonizing bacteria communicating with the gut epithelium
and underlying lymphoid tissues ('bacterial-epithelial crosstalk') result in a
functional immune phenotype and no expression of disease (immune homeostasis).
Appropriate colonization is influenced by the prebiotic effect of breast milk
oligosaccharides. Adequate colonization results in an innate and adaptive mucosal
immune phenotype via communication between molecular patterns on colonizing
bacteria and pattern-recognition receptors (e.g., toll-like receptors) on
epithelial and lymphoid cells. This ontogeny affects the immune system's capacity
to develop oral tolerance to innocuous bacteria and benign antigens. Inadequate
intestinal colonization with premature delivery, delivery by Cesarean section and
excessive use of perinatal antibiotics results in the absence of adequate
bacterial-epithelial crosstalk and an increased incidence of immune-mediated
diseases [e.g., asthma, allergy in general and necrotizing enterocolitis (NEC)].
Fortunately, infants with inadequate intestinal colonization can be restored to a
bacterial balance with the intake of probiotics. This has been shown to prevent
debilitating diseases such as NEC. Thus, understanding the role of gut microbiota
in programming of the immune phenotype may be important in preventing disease
expression in later childhood and adulthood.
PMID- 24353894
TI - A modified fractal zone plate with extended depth of focus in spectral domain
optical coherence tomography.
AB - In optical coherence tomography (OCT) systems, there is a trade-off between the
depth of focus (DOF) and lateral resolution when conventional lenses are used. We
propose a new method that employs a modified fractal generalized zone plate
(MFraGZP) combined with a conventional lens to improve the trade-off effect, with
an extended DOF of about 2.5 mm (14 times larger) while the lateral resolution is
maintained at ~9.5 MUm. As an example, images of the calibration microspheres are
obtained and demonstrated with the extended DOF in a spectral domain OCT system.
PMID- 24353896
TI - Gene expression differences in MSCs and their relevance to osteoporosis.
PMID- 24353897
TI - The role of E-selectin in the vascular HSC niche.
PMID- 24353898
TI - Immune evasion in acute myeloid leukemia: current concepts and future directions.
AB - Immune responses generated against malignant cells have the potential to inhibit
tumor growth, or even eliminate transformed cells before a tumor forms. However,
immune tolerance mechanisms that normally protect healthy tissues from autoimmune
damage pose a formidable barrier to the development of effective anti-tumor
immunity. Because malignant cells are derived from self-tissues, the majority of
defined tumor antigens are either shared or aberrantly expressed self-proteins.
Eliciting productive T cell responses against such proteins is challenging, as
most high-affinity, self-reactive T cells are purged during thymic selection.
Some T cells capable of tumor antigen recognition escape thymic deletion, but are
functionally inhibited by peripheral tolerance mechanisms which limit their
ability to attack a developing malignancy. Alternatively, some tumors express
antigens derived from mutated self-proteins, viral proteins or self proteins
expressed only during embryonic development. These antigens are recognized by the
immune system as foreign and could be recognized by a relatively large number of
peripheral T cells. Even in this scenario, tumors evade otherwise effective T
cell responses by employing potent immunosuppressive mechanisms within their
local environment. In the setting for solid malignancies, such as melanoma, a
growing number of putative immune evasion mechanisms have been characterized.
However, acute myeloid leukemia (AML) is a systemic disease, and the pathways it
exploits to subvert the host immune response may be quite different than those of
a solid tumor. Much remains unknown regarding the immune escape mechanisms
promoted by AML, and whether efforts to thwart tolerance may influence the
progression of this disease. Here, we review current concepts of immune evasion
in AML, and speculate how potentially effective immunotherapeutic strategies
might be developed to reverse immune tolerance in leukemia patients in the
future.
PMID- 24353895
TI - Biological stimuli and biomolecules in the assembly and manipulation of nanoscale
polymeric particles.
AB - Living systems are replete with complex, stimuli-responsive nanoscale materials
and molecular self-assemblies. There is an ever increasing and intense interest
within the chemical sciences to understand, mimic and interface with these
biological systems utilizing synthetic and/or semi-synthetic tools. Our aim in
this review is to give perspective on this emerging field of research by
highlighting examples of polymeric nanoparticles and micelles that are prepared
utilizing biopolymers together with synthetic polymers for the purpose of
developing nanomaterials capable of interacting and responding to biologically
relevant stimuli. It is expected that with the merging of evolved biological
molecules with synthetic materials, will come the ability to prepare complex,
functional devices. A variety of applications will become accessible including
self-healing materials, self-replicating systems, biodiagnostic tools, drug
targeting materials and autonomous, adaptive sensors. Most importantly, the
success of this type of strategy will impact how biomolecules are stabilized and
incorporated into synthetic devices and at the same time, will influence how
synthetic materials are utilized within biomedical applications.
PMID- 24353899
TI - Effect of n-Alkanols on G-Protein alpha Subunits.
AB - Guanine nucleotide binding (G)-proteins are GTP-driven allosteric proteins
consisting of a single alpha subunit and a beta and gamma heterodimer. Galpha
subunits function as on/off switches based on the occupancy of the nucleotide
binding site, GTP or GDP, such that any alteration in nucleotide exchange
modulates signal output. Our previous work has shown that haloalkanes and ethers
inhibit GDP/GTP exchange on alphai1, alphai2 and alphai3 subunits, but not the
closely related alphao. To test whether individual G-protein sensitivity
correlates with n-alkanols potency and hydrophobicity, we studied the effects of
n-alkanols of varied chain lengths on GDP/GTP exchange by Galphasubunits. n
alkanols (ethanol, butanol, pentanol, hexanol, heptanol, octanol and nonanol)
showed differential effects on guanine nucleotide exchange by Galphai1, Galphai2
and Galphao. Based on our observations, we conclude that n-alkanols interact and
modulate the activity of the G-alpha subunits to different extent, thereby
uncoupling pathways known to modulate neuronal excitation.
PMID- 24353901
TI - Cyclophosphamide Induces an Early Wave of Acrolein-Independent Apoptosis in the
Urothelium.
AB - PURPOSE: Hemorrhagic cystitis (HC or bladder inflammation) affects a significant
number of patients undergoing cyclophosphamide (CP) chemotherapy despite
treatment with 2-mercaptoethane sulfonate (Mesna) to inactivate the metabolite
acrolein. While the mechanism is unknown, there is clearly acrolein-independent
damage to the urothelium. In this study we have explored the induction of
apoptosis in the urothelium as a marker of damage and the mechanism underlying
the acrolein-independent apoptosis. MATERIALS AND METHODS: Apoptosis in
urothelium (caspase-3/7 activity and Poly (ADP-ribosyl) polymerase (PARP)
cleavage) was measured following CP administration (80 mg/kg). Sodium 2
mercaptoethane sulfonate (Mesna) was used to mask acrolein's effect. An IL-1beta
receptor antagonist and a cell-permeable caspase-1 inhibitor were used to assess
the involvement of IL-1beta and caspase-1, respectively. RESULTS: Two waves of
apoptosis were detected following CP administration, one peaking at 2 h and a
second at 48 h. The first wave was independent of acrolein. Caspase-1 was also
active at 2 h and activation of caspase-3/7 was blocked by a caspase-1 inhibitor
but not an IL-1beta receptor antagonist suggesting the direct activation of
caspase-3/7 by caspase-1 without the need for IL-1beta as an intermediate.
CONCLUSIONS: Our results indicate that CP initiates an early, acrolein
independent wave of apoptosis that results from direct cleavage of caspase-3/7 by
caspase-1.
PMID- 24353902
TI - Institutions, Politics, and Mental Health Parity.
AB - Mental health parity laws require insurers to extend comparable benefits for
mental and physical health care. Proponents argue that by placing mental health
services alongside physical health services, such laws can help ensure needed
treatment and destigmatize mental illness. Opponents counter that such mandates
are costly or unnecessary. The authors offer a sociological account of the
diffusion and spatial distribution of state mental health parity laws. An event
history analysis identifies four factors as especially important: diffusion of
law, political ideology, the stability of mental health advocacy organizations
and the relative health of state economies. Mental health parity is least likely
to be established during times of high state unemployment and under the
leadership of conservative state legislatures.
PMID- 24353900
TI - Thioredoxin Interacting Protein (TXNIP) and Pathogenesis of Diabetic Retinopathy.
AB - Chronic hyperglycemia (HG)-associated reactive oxygen/nitrogen species (ROS/RNS)
stress and low grade inflammation are considered to play critical roles in the
development of diabetic retinopathy (DR). Excess glucose metabolic flux through
the aldose reductase/polyol pathway, advanced glycation end product (AGE)
formation, elevated hexosamine biosynthesis pathway (HBP), diacyl glycerol/PKC
activation, and mitochondrial ROS generation are all implicated in DR. In
addition, endoplasmic reticulum stress/unfolded protein response (er-UPR) and
deregulation of mitochondrial quality control by autophagy/mitophagy are observed
causing cellular bioenergetic deficiency and injury. Recently, a pro-oxidant and
pro-apoptotic thioredoxin interacting protein (TXNIP) was shown to be highly
upregulated in DR and by HG in retinal cells in culture. TXNIP binds to
thioredoxin (Trx) inhibiting its oxidant scavenging and thiolreducing capacity.
Hence, prolonged overexpression of TXNIP causes ROS/RNS stress, mitochondrial
dysfunction, inflammation and premature cell death in DR. Initially, DR was
considered as microvascular complications of endothelial dysfunction and pericyte
loss characterized by capillary basement membrane thickening, pericyte ghost,
blood retinal barrier leakage, acellular capillary and neovascularization.
However, it is currently acknowledged that neuro-glia are also affected by HG in
diabetes and that neuronal injury, glial activation, innate immunity/sterile
inflammation, and ganglion apoptosis occur early in DR. In addition, retinal
pigment epithelium (RPE) becomes dysfunctional in DR. Since TXNIP is induced by
HG in most cells, its effects are not restricted to a particular cell type in DR.
However, depending on the metabolic activity and anti-oxidant capacity, some
cells may be affected earlier by TXNIP than others. Identification of TXNIP
sensitive cells and elucidating the underlying mechanism(s) will be critical for
preventing pre-mature cell death and progression of DR.
PMID- 24353904
TI - Vernonia amygdalina-Induced Growth Arrest and Apoptosis of Breast Cancer (MCF-7)
Cells.
AB - Breast cancer is the second leading cause of cancer-related deaths of women in
the United States. Fortunately, the mortality rate from breast cancer has
decreased in recent years due to an increased emphasis on early detection and
more effective treatments. Although great advancements have been made in the
treatment and control of cancer progression, significant deficiencies and room
for improvement remain. The central objective of this research was to further
determine the in vitro mechanisms of Vernonia amygdalina (VA) leaf extracts as an
anticancer candidate for the treatment of breast cancer. To achieve our
objective, MCF-7 cells were treated with different concentrations of VA for 24
hand 48 h. Cell viability, live and dead cells were determined by the means of
trypan blue exclusion test. Live and dead cells were further evaluated by
propidium iodine (PI) assay using the Cellometer Vision. Cell apoptosis was
measured by flow cytometry assessment using annexin V/PI kit. Data obtained from
the trypan blue test demonstrated that VA treatment reduces cell viability in a
concentration- and time-dependent manner. Result of the PI assay showed a gradual
increase in the population of necrotic cells (fluorescence positive cells) in VA
treated cells compared to the control cells (fluorescence negative cells).
Treatment of these cancer cells (MCF-7) for 48 h at concentrations ranging from
250 MUg/mL to 1000 MUg/mL caused early signs of apoptosis resulting from
phosphatidylserine externalization as judged by annexin V assay. We observed a
strong concentration-response relationship with regard to VA exposure and annexin
V/PI positive cells. In summary, our finding demonstrates that VA-induced
cytotoxicity and apoptosis in MCF-7 cells involve phosphatidylserine
externalization accompanied by secondary necrotic cell death. With previous
findings in our laboratory, the data generated in the present study confirms that
VA is a valuable botanical therapeutic agent for the treatment of breast cancer.
PMID- 24353903
TI - Fluorescently-Labeled Estradiol Internalization and Membrane Trafficking in Live
N-38 Neuronal Cells Visualized with Total Internal Reflection Fluorescence
Microscopy.
AB - Estradiol is a steroid hormone that binds and activates estradiol receptors.
Activation of these receptors is known to modulate neuronal physiology and
provide neuroprotection, but it is not completely understood how estradiol
mediates these actions on the nervous system. Activation of a sub-population of
estradiol receptor-alpha (ERalpha), originally identified as a nuclear protein,
localizes to the plasma membrane and appears to be a critical step in
neuroprotection against brain injury and disease. Previously we showed that
estradiol stimulates the rapid and transient trafficking of plasma membrane
ERalpha in primary hypothalamic neurons, and internalization of membrane
impermeant estradiol (E6BSA-FITC) into cortical neuron endosomes in vitro. These
findings support the concept that estradiol activates and down-regulates plasma
membrane ERalpha by triggering endocytosis. Here, we use TIRFM (total internal
reflection fluorescence microscopy) to image the trafficking of E6BSA-FITC, and
GFP-labeled ERalpha, in live cells in real time. We show that activation of
plasma membrane ERs by E6BSA-FITC result in internalization of the fluorescent
ligand in live N-38 neurons, an immortalized hypothalamic cell line. Pretreatment
with ER antagonist ICI 182,780 decreased the number of E6BSA-FITC labeled puncta
observed. We also observed in live N-38 neurons that E6BSA-FITC co-localized with
FM4-64 and LysoTracker fluorescent dyes that label endosomes and lysosomes. Our
results provide further evidence that plasma membrane ERalpha activation results
in endocytosis of the receptor.
PMID- 24353905
TI - Hereditary leukemia due to rare RUNX1c splice variant (L472X) presents with
eczematous phenotype.
AB - Deleterious mutations in the RUNX1 gene cause hereditary leukemia due to a rare
syndrome called Familial platelet Disorder with Associated Myeloid Malignancy
(FPDMM). We describe the characteristics of a family with FPDMM due to a novel
RUNX1 mutation (L472X), located in the most 3-prime end of the gene reported to
date. Our 36-year old proband presented with incidentally detected
thrombocytopenia and a family history suggestive of FPDMM. Contrary to previously
described families, affected members of our kindred express an eczematous
phenotype, reportedly most severe in members who develop leukemia. Pedigree
analysis shows that the L472X mutation tracks with thrombocytopenia, acute
leukemia, and eczema. The L472X mutation produces a stably expressed RUNX1
protein product with a corresponding decrease in wild type RUNX1 expression. Our
data supports the inclusion of eczema in the FPDMM phenotype and suggests the
possibility that the RUNX1 L472X mutant causes the type of dominant negative
affect that is associated with an elevated risk of leukemia in FPDMM families.
PMID- 24353906
TI - A Systematic Review of Health Videogames on Childhood Obesity Prevention and
Intervention.
AB - Childhood obesity is a global epidemic. Health videogames are an emerging
intervention strategy to combat childhood obesity. This systematic review
examined published research on the effect of health videogames on childhood
obesity. Fourteen articles examining 28 health videogames published between 2005
and 2013 in English were selected from 2433 articles identified through five
major search engines. Results indicated that academic interest in using health
videogames for childhood obesity prevention has increased during this time. Most
games were commercially available. Most studies were of short duration. Diverse
player and game play patterns have been identified. Most studies involved players
of both genders with slightly more boys. The majority of players were non-white.
Most studies had the players play the games at home, whereas some extended the
play setting to school and sports/recreational facilities. Most of the games were
commercially available. Positive outcomes related to obesity were observed in
about 40 percent of the studies, all of which targeted overweight or obese
participants.
PMID- 24353907
TI - Intratumoral mast cells promote the growth of pancreatic cancer.
AB - We have recently discovered that mast cells promote pancreatic tumorigenesis by
exacerbating the cellular and extracellular signaling in the desmoplastic
microenvironment. Our findings demonstrate for the first time that targeting mast
cells can block the progression of pancreatic neoplasms and prolong the survival
of tumor-bearing immunocompetent hosts.
PMID- 24353909
TI - Is there a future for adoptive cell transfer in melanoma patients?
AB - The adoptive transfer of tumor-infiltrating lymphocytes (TILs) can yield durable
responses in patients affected by metastatic melanoma. In particular, we have
recently reported an 80% 3 year survival rate among patients who responded to
this immunotherapeutic regimen. Of note, overall response rates were equal among
ipilimumab-naive and ipilimumab-refractory patients. Thus, the adoptive transfer
of TILs, as a standalone therapeutic intervention or combined with other
treatment modalities, bears a high clinical potential that must be optimally
employed.
PMID- 24353908
TI - New prospects on the NKG2D/NKG2DL system for oncology.
AB - The activating immunoreceptor NKG2D endows cytotoxic lymphocytes with the
capacity to recognize and eliminate infected or malignant cells. The recognition
of such harmful cells is enabled by binding of NKG2D to various MHC class I
related glycoproteins, which are upregulated in the course of viral infection or
malignant transformation. The past years have witnessed substantial progress in
our understanding of the mechanisms underlying the regulation of NKG2D ligands
(NKG2DLs) by malignant cells, of tumor-associated countermeasures promoting
escape from NKG2D-dependent immunosurveillance, and of therapeutic measures that
may bolster the NKG2D/NKG2DL system against malignancies. Here, we summarize the
current knowledge on the NKG2D/NKG2DL system and outline opportunities to exploit
the tumoricidal function of NKG2D for anticancer immunotherapy.
PMID- 24353910
TI - Autophagy-dependent suppression of cancer immunogenicity and effector mechanisms
of innate and adaptive immunity.
AB - The inspection of the mechanisms through which autophagy modulates immunogenic
cell death revealed that the autophagic response of cancer cells to reactive
oxygen species-dependent endoplasmic reticulum stress suppresses the exposure of
calreticulin on the cell surface, the phenotypic maturation of dendritic cells
(DCs) as well as their ability to release interleukin-6 and to support the
proliferative expansion of (interferon gamma-producing) CD4+ and CD8+ T
lymphocytes. These findings unveil an unprecedented role for therapy-induced
autophagy in suppressing key mechanisms that underlie anticancer immune responses
as elicited by immunogenic cell death.
PMID- 24353911
TI - Potentiating antitumor immunity with alphaGC-loaded exosomes.
AB - Anticancer immunotherapy is a promising treatment modality since it bears the
potential of being highly specific, but effective clinical applications are still
under development. We have recently described an exosome-based strategy for co
delivery of alpha-galactosylceramide and a tumor-associated antigen that
synergistically potentiates tumor-specific adaptive immune responses while
preventing the anergy of invariant natural killer T (iNKT) cells. We propose that
the next generation of exosome-based immunotherapies should involve iNKT-cell
ligands to induce a broad, amplified and sustainable antitumor immune response.
PMID- 24353912
TI - Blockade of PD-1 immunosuppression boosts CAR T-cell therapy.
AB - The presence of an immunosuppressive microenvironment can limit the full
potential of adoptive T cell immunotherapy. However, specific blockade of the PD
1 immunosuppressive pathway can significantly enhance the function of gene
modified T cells expressing a chimeric antigen receptor (CAR) leading to enhanced
tumor eradication.
PMID- 24353913
TI - APLP2 regulates the expression of MHC class I molecules on irradiated Ewing's
sarcoma cells.
AB - Ewing's sarcoma (EWS) is a pediatric cancer that is conventionally treated by
surgery, chemotherapy, and radiation therapy. Innovative immunotherapies to treat
EWS are currently under development. Unfortunately for EWS patients, when the
disease is found to be resistant to current therapeutic approaches, the prognosis
is predictably grim. Radiation therapy and immunotherapy could potentially
synergize in the eradication of EWS, as some studies have previously shown that
irradiation increases the presence of immune receptors, including MHC class I
molecules, on the surface of tumor cells. However, EWS cells have been reported
to express low levels of MHC class I molecules, a phenotype that would inhibit T
cell mediated lysis. We have previously demonstrated that the transgene-driven
overexpression of amyloid beta (A4) precursor-like protein 2 (APLP2) reduces the
expression of MHC class I molecules on the surface of human cervical carcinoma
HeLa cells. We thus examined whether endogenously expressed APLP2 downregulates
MHC class I expression on EWS cells, particularly upon irradiation. We found that
irradiation induces the relocalization of APLP2 and MHC class I molecules on the
surface of EWS cells, redistributing cells from subpopulations with relatively
low APLP2 and high MHC class I into subpopulations with relatively high APLP2 and
low MHC class I surface expression. Consistent with these findings, the
transfection of an APLP2-targeting siRNA into EWS cells increased MHC class I
expression on the cell surface. Furthermore, APLP2 was found by co
immunoprecipitation to bind to MHC class I molecules. Taken together, these
findings suggest that APLP2 inhibits MHC class I expression on the surface of
irradiated EWS cells by a mechanism that involves APLP2/MHC class I interactions.
Thus, therapeutic strategies that limit APLP2 expression may boost the ability of
T cells to recognize and eradicate EWS in patients.
PMID- 24353915
TI - The relationship between malignant and tumor-associated cells provides a new
strategy for targeted diagnosis and therapy.
AB - Here, we discuss the intimate relationship that exists between malignant and
tumor-associated cells, providing a new strategy for targeted diagnosis and
therapy via the screening of single-chain antibodies and aptamers that interact
with target cells.
PMID- 24353914
TI - Effects of conventional therapeutic interventions on the number and function of
regulatory T cells.
AB - Several lines of investigation have revealed the apparent interplay between the
immune system of the host and many conventional, "standard-of-care" anticancer
therapies, including chemotherapy and small molecule targeted therapeutics. In
particular, preclinical and clinical studies have demonstrated the important role
of regulatory T cells (Tregs) in inhibiting immune responses elicited by
immunotherapeutic regimens such as those based on anticancer vaccines or
checkpoint inhibitors. However, how the number and immunosuppressive function of
Tregs change in cancer patients undergoing treatment with non-immune anticancer
therapies remains to be precisely elucidated. To determine whether
immunostimulatory therapies can be employed successfully in combination with
conventional anticancer regimens, we have investigated both the number and
function of Tregs obtained from the peripheral blood of carcinoma patients before
the initiation and during the course of chemotherapeutic and targeted agent
regimens. Our studies show that the treatment of breast cancer patients with
tamoxifen plus leuprolide, a gonadotropin releasing hormone agonist, has minimal
effects on Tregs, while sunitinib appears to exert differential effects on Tregs
among patients with metastatic renal carcinoma. However, the administration of
docetaxel to patients with metastatic prostate or breast cancer, as well as that
of cisplatin plus vinorelbine to non-small cell lung cancer patients, appears to
significantly increase the ratio between effector T cells and Tregs and to reduce
the immunosuppressive activity of the latter in the majority of patients. These
studies provide the rationale for the selective use of active immunotherapy
regimens in combination with specific standard-of-care therapies to achieve the
most beneficial clinical outcome among carcinoma patients.
PMID- 24353916
TI - Non-replicating Toxoplasma gondii reverses tumor-associated immunosuppression.
AB - We examined the efficacy of using attenuated non-replicating Toxoplasma gondii
uracil auxotrophs that can be safely delivered as anticancer immunotherapeutics.
This strategy exerted remarkable therapeutic activity in murine models of
melanoma and ovarian carcinoma, and holds broad potential for the development of
novel, highly effective anticancer vaccines.
PMID- 24353917
TI - Survivin-3B promotes chemoresistance and immune escape by inhibiting caspase-8
and -6 in cancer cells.
AB - Survivin-3B (S-3B), an alternative splice isoform of survivin, plays a key role
in tumorigenesis. S-3B promotes the escape of malignant cells from immune
recognition by blocking the cytotoxicity of natural killer (NK) cells. Such an
effect reflects the ability of S-3B to interfere with the assembly of the so
called "death-inducing signaling complex" upon the interaction of FAS with its
ligand (FASL). S-3B also inhibits the activation of caspase-6, thus increasing
the resistance of neoplastic cells to granzyme B and various chemotherapeutics.
PMID- 24353918
TI - Crucial role of inflammatory monocytes in antitumor immunity.
AB - Although the role of myeloid cells in oncogenesis and tumor progression remains
poorly understood, these cells are mainly ascribed with pro-tumor properties. We
have recently unveiled a tumoricidal activity of inflammatory monocytes that can
be counteracted by CD4+ regulatory T cells.
PMID- 24353919
TI - REG3beta contributes to the immunosuppressive microenvironment of pancreatic
cancer.
AB - The levels of regenerating islet-derived 3beta (REG3beta) in the serum and
pancreatic juice of patients affected by pancreatic ductal adenocarcinomas are
increased. However, whether such an elevation is relevant to oncogenesis and
tumor progression has not yet been carefully examined. We have recently
demonstrated that silencing REG3beta in a pancreatic cancer model impairs tumor
growth by skewing macrophage polarization.
PMID- 24353920
TI - Monocyte-derived dendritic cells: Emerging players in the antitumor immune
response.
AB - The elicitation of efficient antitumor immune responses requires the optimal
activation of tumor-associated dendritic cells (DCs). Our comparison of the
effect of various immunostimulatory treatments on DCs revealed that the best
predictor of the success of immunotherapy is not the activation of existing DC
populations, but the appearance of a population of monocyte-derived DC in tumor
draining lymph nodes.
PMID- 24353921
TI - Primary dystonia misinterpreted as Parkinson disease: Video case presentation and
practical clues.
AB - Diagnosing dystonia can be challenging and depends on the recognition of subtle
clinical signs. Due to clinical heterogeneity, variable age at presentation, and
overlapping features with other disorders, dystonia is under-recognized. The
presence of dystonic tremor is often a reason for misdiagnosis. We report an
illustrative case of a patient with DYT1 dystonia who was originally misdiagnosed
with Parkinson disease. Careful physical examination and history-taking can
reveal dystonia and prompt appropriate diagnostic studies, which, in turn, can
lead to potentially life-changing treatment. Our report illustrates typical
challenges in the recognition and diagnosis of dystonia, and serves to increase
clinicians' awareness of this disabling, but treatable, condition.
PMID- 24353922
TI - Neurorehabilitation: Five new things.
AB - Neurologists have a new toolbox of options for neurorehabilitation of disabling
brain disorders such as stroke and traumatic brain injury. An emerging
intellectual paradigm for neurologic recovery that includes neural regeneration,
repair, and dynamic reorganization of functional neural systems, as well as
increasing awareness of behavioral principles that may support best return to
function and freedom, brought forward treatments based on experience-dependent
learning, neurophysiologic stimulation, and a combination of these concepts. In
this article, we summarize five rehabilitative approaches to watch: constraint
therapy for motor and language recovery, synergy of motor-language
rehabilitation, prism adaptation training and other virtual feedback approaches,
and noninvasive magnetic and electrical brain stimulation.
PMID- 24353923
TI - Transcranial magnetic stimulation in neurology: A review of established and
prospective applications.
AB - Transcranial magnetic stimulation (TMS) is a neurophysiologic technique to
noninvasively induce a controlled current pulse in a prespecified cortical
target. This can be used to transiently disrupt the function of the targeted
cortical region and explore causal relations to behavior, assess cortical
reactivity, and map out functionally relevant brain regions, for example during
presurgical assessments. Particularly when applied repetitively, TMS can modify
cortical excitability and the effects can propagate trans-synaptically to
interconnected cortical, subcortical, and spinal cord regions. As such, TMS can
be used to assess the functional integrity of neural circuits and to modulate
brain activity with potential therapeutic intent.
PMID- 24353924
TI - Nonmydriatic retinal photography in the evaluation of acute neurologic
conditions.
AB - Ocular fundus examination is a fundamental component of the neurologic
examination. Finding papilledema in headache patients or retinal arterial emboli
in stroke patients can be extremely useful. Although examination of the ocular
fundus with a direct ophthalmoscope is an important skill for all neurologists,
it is rarely and unreliably performed. Nonmydriatic ocular fundus photography,
which allows direct visualization of high-quality photographs of the ocular
fundus, has been recently proposed for screening neurologic patients in urgent
care settings such as emergency departments. This new technology has many
potential applications in neurology, including e-transmission of images for
remote interpretation.
PMID- 24353925
TI - Lessons Learned from a Community Based Lifestyle Intervention for Youth at Risk
for Type 2 Diabetes.
AB - PURPOSE: This pilot study examined the feasibility and acceptability of a peer
led diabetes prevention intervention for youth in an underserved community.
METHODS: Children and adolescents randomized to the intervention group
participated in a one year program which included peer support, physical
activity, and family nutrition, and behavior modification sessions. Participants
were asked about their satisfaction with the study and possible benefits, what
they learned, and whether they would recommend participation to a friend. Youth
randomized to the control group received monthly healthy lifestyle educational
materials through the mail. RESULTS: Children and adolescents (n=67) with an
average age of 12.5 years and BMI greater than or equal to 85 percentile for age
and sex were enrolled in the study. The average monthly participation rate varied
between 90 and 50 percent with a mean rate of 82 percent. Ninety four percent of
parents reported being very satisfied with the program and all (100%) reported
they would recommend the program to a friend. All the children and adolescents
(100%) reported that they enjoyed working with the youth peer coaches and 94%
felt their assigned coach was a good role model. The observed changes in BMI z
score trended towards improvement in the intervention group, but this study was
underpowered to detect differences between groups. CONCLUSION: The peer led
diabetes prevention program was feasible and acceptable and demonstrated
potential for improving health behaviors.
PMID- 24353926
TI - Video-rate resonant scanning multiphoton microscopy: An emerging technique for
intravital imaging of the tumor microenvironment.
AB - The abnormal tumor microenvironment fuels tumor progression, metastasis, immune
suppression, and treatment resistance. Over last several decades, developments in
and applications of intravital microscopy have provided unprecedented insights
into the dynamics of the tumor microenvironment. In particular, intravital
multiphoton microscopy has revealed the abnormal structure and function of tumor
associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug
delivery, invasion and metastasis of tumor cells, the dynamics of immune cell
trafficking to and within tumors, and gene expression in tumors. However,
traditional multiphoton microscopy suffers from inherently slow imaging rates
only a few frames per second, thus unable to capture more rapid events such as
blood flow, lymphatic flow, and cell movement within vessels. Here, we report the
development and implementation of a video-rate multiphoton microscope (VR-MPLSM)
based on resonant galvanometer mirror scanning that is capable of recording at 30
frames per second and acquiring intravital multispectral images. We show that the
design of the system can be readily implemented and is adaptable to various
experimental models. As examples, we demonstrate the utility of the system to
directly measure flow within tumors, capture metastatic cancer cells moving
within the brain vasculature and cells in lymphatic vessels, and image acute
responses to changes in a vascular network. VR-MPLSM thus has the potential to
further advance intravital imaging and provide new insight into the biology of
the tumor microenvironment.
PMID- 24353927
TI - Bifunctional nanoarrays for probing the immune response at the single-molecule
level.
AB - Bifunctional nanoarrays were created to simulate the immunological synapse and
probe the T-cell immune response at the single-molecule level. Sub-5 nm AuPd
nanodot arrays were fabricated using both e-beam and nanoimprint lithography. The
nanoarrays were then functionalized by two costimulatory molecules: antibody
UCHT1 Fab, which binds to the T-cell receptor (TCR) and activates the immune
response, bound to metallic nanodots; and intercellular adhesion molecule-1,
which enhances cell adhesion, on the surrounding area. Initial T-cell experiments
show successful attachment and activation on the bifunctional nanoarrays. This
nanoscale platform for single-molecule control of TCR in living T-cells provides
a new approach to explore how its geometric arrangement affects T-cell activation
and behavior, with potential applications in immunotherapy. This platform also
serves as a general model for single-molecule nanoarrays where more than one
molecular species is required.
PMID- 24353928
TI - Nanorough gold for enhanced Raman scattering.
AB - Conventional Raman scattering is a workhorse technique for detecting and
identifying complex molecular samples. In surface enhanced Raman scattering, a
nanorough metallic surface close to the sample enhances the Raman signal
enormously. In this work, the surface is on a clear epoxy substrate. The epoxy is
cast on a silicon wafer, using 20 nm of gold as a mold release. This single step
process already produces useful enhanced Raman signals. However, the Raman signal
is further enhanced by (1) depositing additional gold on the epoxy substrate and
(2) by using a combination of wet and dry etches to roughen the silicon substrate
before casting the epoxy. The advantage of a clear substrate is that the Raman
signal may be obtained by passing light through the substrate, with opaque
samples simply placed against the surface. Results were obtained with solutions
of Rhodamine 6G in deionized water over a range of concentrations from 1 nM to 1
mM. In all cases, the signal to noise ratio was greater than 10:1.
PMID- 24353929
TI - Gsta4 Null Mouse Embryonic Fibroblasts Exhibit Enhanced Sensitivity to Oxidants:
Role of 4-Hydroxynonenal in Oxidant Toxicity.
AB - The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.18)
exhibits high catalytic efficiency to-wards 4-hydroxynon-2-enal (4-HNE), a major
end product of oxidative stress induced lipid peroxidation. Exposure of cells and
tissues to heat, radiation, and chemicals has been shown to induce oxidative
stress resulting in elevated concentrations of 4-HNE that can be detrimental to
cell survival. Alternatively, at physiological levels 4-HNE acts as a signaling
molecule conveying the occurrence of oxidative events initiating the activation
of adaptive pathways. To examine the impact of oxidative/electrophilic stress in
a model with impaired 4-HNE metabolizing capability, we disrupted the Gsta4 gene
that encodes GSTA4-4 in mice. The effect of electrophile and oxidants on
embryonic fibroblasts (MEF) isolated from wild type (WT) and Gsta4 null mice were
examined. Results indicate that in the absence of GSTA4-4, oxidant-induced
toxicity is potentiated and correlates with elevated accumulation of 4-HNE
adducts and DNA damage. Treatment of Gsta4 null MEF with 1,1,4-tris(acetyloxy)
2(E)-nonene [4-HNE(Ac)3], a pro-drug form of 4-HNE, resulted in the activation
and phosphorylation of the c-jun-N-terminal kinase (JNK), extracellular-signal
regulated kinases (ERK 1/2) and p38 mitogen activated protein kinases (p38 MAPK)
accompanied by enhanced cleavage of caspase-3. Interestingly, when recombinant
mammalian or invertebrate GSTs were delivered to Gsta4 null MEF, activation of
stress-related kinases in 4-HNE(Ac)3 treated Gsta4 null MEF were inversely
correlated with the catalytic efficiency of delivered GSTs towards 4-HNE. Our
data suggest that GSTA4-4 plays a major role in protecting cells from the toxic
effects of oxidant chemicals by attenuating the accumulation of 4-HNE.
PMID- 24353931
TI - Minimally Invasive versus Open Cervical Foraminotomy: A Systematic Review.
AB - Posterior cervical laminoforaminotomy is an effective treatment for cervical
radiculopathy due to disc herniations or spondylosis. Over the last decade,
minimally invasive (i.e., percutaneous) procedures have become increasingly
popular due to a smaller incision size and presumed benefits in postoperative
outcomes. We performed a systematic review of the literature and identified
studies of open or percutaneous laminoforaminotomy that reported one or more
perioperative outcomes. Of 162 publications found by our initial screening, 19
were included in the final analysis. Summative results indicate that patients
undergoing percutaneous cervical laminoforaminotomy have lower blood loss by
120.7 mL (open: 173.5 mL, percutaneous: 52.8 mL, n = 670), a shorter surgical
time by 50.0 minutes (open: 108.3 minutes, percutaneous: 58.3 minutes, n = 882),
less inpatient analgesic use by 25.1 Eq (open: 27.6 Eq, percutaneous: 2.5 Eq, n =
356), and a shorter hospital stay by 2.2 days (open: 3.2 days, percutaneous: 1.0
days, n = 1472), compared with patients undergoing open procedures. However, the
heterogeneous nature of published data calls into question the reliability of
these summative results. Further structured trials should be conducted to better
characterize the risks and benefits of percutaneous laminoforaminotomy.
PMID- 24353930
TI - Diagnosis and prognosis of traumatic spinal cord injury.
AB - Despite promising advances in basic spinal cord repair research, no effective
therapy resulting in major neurological or functional recovery after traumatic
spinal cord injury (tSCI) is available to date. The neurological examination
according to the International Standards for Neurological and Functional
Classification of Spinal Cord Injury Patients (International Standards) has
become the cornerstone in the assessment of the severity and level of the injury.
Based on parameters from the International Standards, physicians are able to
inform patients about the predicted long-term outcomes, including the ability to
walk, with high accuracy. In those patients who cannot participate in a reliable
physical neurological examination, magnetic resonance imaging and
electrophysiological examinations may provide useful diagnostic and prognostic
information. As clinical research on this topic continues, the prognostic value
of the reviewed diagnostic assessments will become more accurate in the near
future. These advances will provide useful information for physicians to counsel
tSCI patients and their families during the catastrophic initial phase after the
injury.
PMID- 24353932
TI - Cauda equina syndrome following decompression for spinal stenosis.
AB - Cauda equina syndrome following decompression for spinal stenosis appears to
occur more commonly than the literature suggests. A large series of spinal
stenosis decompressions was reviewed. Based on these findings, a theory is put
forth as to the cause of this complication. One hundred seventy-five cases of
decompression for spinal stenosis done over a 2.5-year period were reviewed.
Follow-up was 1year to 2 years and 4 months. There were 14 cases of postoperative
urinary retention, for an incidence of 8%. Of those, five were ultimately
diagnosed with cauda equina syndrome, for an incidence of 2.8%. Of the nine cases
that were not diagnosed as cauda equina syndrome, five resolved spontaneously
over 2 to 6 weeks. The remaining four were diagnosed as having mechanical urinary
problems (e.g., prostate or prolapsed bladder) that required surgical treatment.
Anal sphincter monitoring at the time of surgery was not predictive in those
patients who developed cauda equina syndrome. All patients who developed cauda
equina syndrome improved over 3 to 9 months, but none completely resolved. Three
cases underwent further decompression with no apparent improvement. Cauda equina
syndrome occurs in 2.8% of decompressions for spinal stenosis.
PMID- 24353933
TI - Primary cerebellar tuberculoma in Arnold-Chiari malformation mimicking posterior
cranial fossa tumor: the first report.
AB - Chiari malformations are a congenital heterogeneous group of disorders
characterized by anatomic anomalies of the cerebellum, brain stem, and
craniocervical junction associated with downward displacement of the cerebellum,
alone or with lower medulla, into the cervical spine canal. The patient was a 23
year-old woman, a known case of Arnold-Chiari malformation with peripheral
neuropathy and muscular atrophy, who presented with headache, drowsiness,
decreased vision, and severe gait dysfunction lasting for several years. Brain
magnetic resonance imaging confirmed a hypointense signal mass in the left
hemisphere of the cerebellum causing mass effects on the fourth ventricle, which
shifted it, accompanied with dilation of third and lateral ventricles.
PMID- 24353934
TI - Thoracic Fracture through a Prior Instrumented Arthrodesis in a Patient with
Ankylosing Spondylitis without Hardware Loosening: A Case Report.
AB - The objective of this article is to report a case of a patient with ankylosing
spondylitis who sustained a fracture through a prior solid arthrodesis without
loosening or changing posterior instrumentation. There have been few cases
reported of a patient with ankylosing spondylitis suffering a fracture through a
prior instrumented arthrodesis. None have noted the instrumentation remaining
intact with the fracture through the middle of the construct. The surgeon must be
aware of this possibility to avoid spinal instability that may lead to a
neurological deficit. We retrospectively reviewed the case. A review of the
literature was performed through a PubMed search. A patient was found to have a
fracture within a prior construct despite the presence of a posterior
instrumentation. The mechanism of failure was a three-column spine fracture with
"bending" of the rods. This patient was treated with a revision
posterior/anterior instrumentation and fusion with placement of larger-diameter
rods for added stiffness. Fractures through a prior instrumented arthrodesis are
rare but still can occur in the ankylosing spondylitis patient. Given the higher
risk of epidural hematoma and neurological compromise in this patient population,
the surgeon must keep this on the differential diagnosis when treating patients
with a prior instrumented arthrodesis.
PMID- 24353935
TI - The proximal thoracic curve in adolescent idiopathic scoliosis: surgical strategy
and management outcomes.
AB - There is no consensus on the definition of a structural proximal thoracic curve
(PTC) and the indications for fusion. As such, we assessed a single institute's
experience in the management of large PTCs (>35 degrees) in patients with
adolescent idiopathic scoliosis (AIS) who were either fused or not fused. A
retrospective radiographic analyses of 30 consecutive AIS patients with double
thoracic curves who underwent PSF with a minimum of 2 years' follow-up were
included for review. The patients were divided into two groups: group 1 (n = 15
patients) with fusion extended up to T2 or T3 and group 2 (n = 15) with fusion
limited to T5 or below. Shoulder balance was assessed according to clavicular
angle, first-rib difference, and radiographic shoulder height difference (SHD).
PTCs were defined based on a Cobb angle of >35, the presence of apical rotation,
and a positive T1 tilt. The decision to fuse the PTC was based on curve magnitude
only, with those between 35 and 45 degrees undergoing a selective fusion of the
main thoracic curve (MTC), with both curves fused if the PTC was more than 45
degrees. In group 1, there were eight females and seven males. Their ages ranged
between 12 and 33 years, with a mean of 16.2 +/- 5.5 years. Postoperatively, the
mean PTC correction was 45.6%, which statistically differed from preoperative
status (p = 0.001). No statistical difference was noted in T1 tilt and the first
rib difference from preoperative to postoperative follow-up (p > 0.05). However,
the clavicular angle and SHD were increased significantly at the immediate
postoperative interval (p < 0.05) but demonstrated no significant changes between
the initial and the last follow-up values (p > 0.05). Group 2 consisted of one
male and 14 females. The mean age was 16.4 +/- 4 years (range: 11 to 28 years).
The mean spontaneous PTC correction was 28.3% and remained essentially unchanged
at the end of the follow-up. The improvement in the curve from preoperative
status was highly statistically significant (p = 0.001). All radiographic
shoulder parameters exhibited a significant increase in the immediate
postoperative period and at last follow-up, and shoulder balance improvement was
not noted on follow-up. Although both groups were not statistically similar with
regards to the preoperative PTC, AVR, apical vertebral translation, and shoulder
parameters, no significant difference could be found in PTC or shoulder
parameters between both groups at last follow-up (p > 0.05). Our study
illustrates important observations that should be considered in defining the PTC
for fusion consideration. Spontaneous correction of the PTC occurs in structural
curves greater than 35 degrees and less than 45 degrees, and this correction is
maintained over time. Despite that correction, radiographic shoulder parameters
are expected to slightly increase. Nonfusion strategy may be appropriate for PTCs
between 35 and 45 degrees. After fusion of both the MTC and the PTC, the
radiographic shoulder parameters did not significantly differ. Preoperative
radiographic shoulder parameters are not predictive of postoperative shoulder
imbalance.
PMID- 24353936
TI - Craniocervical traumatic injuries: evaluation and surgical decision making.
AB - We present a literature review of current approaches to craniocervical traumatic
injuries. In an attempt to categorize the injuries that involve the upper
cervical spine, we divide the injuries into two groups: (1) injuries affecting
mainly bone structures and (2) predominantly ligamentous injury. This division is
based on the principle that bone injuries have the potential to heal with
conservative treatment whereas ligamentous injury would not heal properly,
leading to an unstable spine. An accurate diagnosis and treatment are necessary
to improve patient's outcome and avoid complications. As a general rule,
ligamentous injuries are unstable lesions, requiring surgical treatment. Bony
injuries can be conservatively treated, with surgery reserved for more unstable
patterns (unstable C1 ring, displaced odontoid or C2 pars fractures).
PMID- 24353937
TI - Kinematic Evaluation of Association between Disc Bulge Migration, Lumbar
Segmental Mobility, and Disc Degeneration in the Lumbar Spine Using Positional
Magnetic Resonance Imaging.
AB - Degenerative disc disease and disc bulge in the lumbar spine are common sources
of lower back pain. Little is known regarding disc bulge migration and lumbar
segmental mobility as the lumbar spine moves from flexion to extension. In this
study, 329 symptomatic (low back pain with or without neurological symptoms)
patients with an average age of 43.5 years with varying degrees of disc
degeneration were examined to characterize the kinematics of the lumbar
intervertebral discs through flexion, neutral, and extension weight-bearing
positions. In this population, disc bulge migration associated with dynamic
motion of the lumbar spine significantly increased with increased grade of disk
degeneration. Although no obvious trends relating the migration of disc bulge and
angular segmental mobility were seen, translational segmental mobility tended to
increase with disc bulge migration in all of the degenerative disc states. It
appears that many factors, both static (intervertebral disc degeneration or disc
height) and dynamic (lumbar segmental mobility), affect the mechanisms of lumbar
disc bulge migration.
PMID- 24353938
TI - A new beginning.
PMID- 24353939
TI - The incidence of infection after posterior cervical spine surgery: a 10 year
review.
AB - Background The incidence of infection after posterior cervical spine surgery
ranges from 0 to 18%. Higher rates have been reported after posterior procedures
compared with anterior procedures, but these studies have been for small series.
We report on our rate of surgical site infection (SSI) after posterior cervical
spine surgery and the risk factors that influence these infections. Methods We
retrospectively reviewed the records of 90 consecutive patients who underwent
posterior cervical spine procedures at a major spinal referral center between
1998 and 2007. The main indications for surgery were trauma and degenerative
conditions. Tumors and primary infections were excluded. Medical records of these
patients were examined for evidence of SSI as diagnosed by Centers for Disease
Control and Prevention criteria. Results Using stringent criteria for diagnosing
SSI, we found 15 infected patients (16.67%). The postoperative use of a
Philadelphia hard collar was found to be a significant risk factor for SSI with a
relative risk of 15.30 (95% confidence interval 2.10 to 111.52). Almost half of
infected patients (47%) required reoperation for wound debridement, with four
requiring skin flap closure. All 15 patients had successful outcomes with
complete resolution of their infection. Conclusions This study confirms a high
incidence of SSI after posterior cervical surgery. The most significant risk
factors for SSI were found to be a traumatic etiology and postoperative use of a
collar. We believe it is important to develop strategies to minimize the risk of
infection after posterior cervical surgery, which include questioning the
postoperative use of collars.
PMID- 24353940
TI - Rationale of revision lumbar spine surgery.
AB - Revision lumbar spine surgeries are technically challenging with inconstant
outcome results. This article discusses the preoperative, intraoperative, as well
as postoperative management in these difficult patients. Successful intervention
requires a detailed history and physical examination and carefully chosen
diagnostic tests. Preoperative planning is paramount in these cases. The decision
making process should address the timing of the surgery, surgical approach, level
of interbody fusion required, correction of sagittal imbalance, type of
osteotomy, location of the osteotomy, and the end of the construct. Surgeons
should be prepared to manage associated complications such as dural tear and
massive blood loss. The use of autograft and/or biologic graft is necessary to
help in achieving a successful fusion. Postoperative management includes
prophylactic antibiotic, anticoagulation, nutritional support, and brace.
PMID- 24353941
TI - Open-door cervical laminoplasty with preservation of posterior structures.
AB - Objective To demonstrate that preservation of all posterior structures during
open-door laminoplasty (ODL) is associated with a significant preservation of
motion. Methods Fifteen patients underwent cervical ODL by one surgeon for
treatment of cervical spondylotic myelopathy. An open-door technique was
employed, and the laminae on the open side were reconstructed using miniplates
with allograft strut bone graft. All spinous processes and interspinous and
supraspinous ligaments were preserved within the operative levels and between
supra- and subjacent levels in all patients. Postoperative radiographs were
obtained 1.5, 3, 6, and 12 months. Computed tomography scans were obtained at 12
months. Results There were no significant intraoperative or perioperative
complications. Postoperatively, the neutral angle was 6.8 +/- 11.5 degrees (95%
confidence interval: 0.5 to 13.1), representing a loss of lordosis of 3 degrees
(not significant). The difference between the preoperative and postoperative arc
range of motion was 5.96 +/- 11.9 degrees (confidence interval: -0.62 to 12.5).
The average percent loss of motion was 3.5% +/- (0.1 to 6.9%). Four patients had
an increased range of motion postoperatively. Conclusion Open-door laminoplasty
with preservation of all posterior structures provides greater preservation of
motion than has been previously described.
PMID- 24353942
TI - Good functional outcome and adjacent segment disc quality 10 years after single
level anterior lumbar interbody fusion with posterior fixation.
AB - We reviewed the records of a prospective consecutive cohort to evaluate the
clinical performance of anterior lumbar interbody fusion with a titanium box cage
and posterior fixation, with emphasis on long-term functional outcome. Thirty-two
patients with chronic low back pain underwent anterior lumbar interbody fusion
and posterior fixation. Radiological and functional results (visual analogue
scale [VAS] and Oswestry score) were evaluated. Adjacent segment degeneration
(ASD) was evaluated radiologically and by magnetic resonance imaging (MRI).
Twenty-five patients (78%) were available for follow-up. Functional scores showed
significant improvement in pain and function up to the 2-year follow-up
observation. At 4 years, there was some deterioration of the clinical results. At
10-year follow-up, results remained stable compared with 4-year results. MRI
showed ASD in 3/25 (12%) above and 2/10 (20%) below index level (compared with
absent preoperatively). ASD could not be related to clinical outcome in this
study. Anterior lumbar interbody fusion and posterior fixation is safe and
effective. Initial improvement in VAS and Oswestry scores is partly lost at the 4
year follow-up. Good clinical results are maintained at 10-year follow-up and are
not related to adjacent segment degeneration.
PMID- 24353943
TI - Dispersal pattern of injectate after lumbar interlaminar epidural spinal
injection evaluated with computerized tomography.
AB - Study Design Retrospective analysis of lumbar computed tomographic epidurograms.
Objective To evaluate the dispersal pattern of injectate after interlaminar
lumbar epidural steroid injections. Summary Prior studies have evaluated the
dispersal patterns of injectate after lumbar epidural steroid injections using
fluoroscopy with varying results. To date, there have been no studies evaluating
the dispersal pattern utilizing computerized tomography. Methods Ten epidurograms
were analyzed after lumbar interlaminar epidural steroid injection. The
epidurograms were examined, evaluating the dispersal pattern in longitudinal flow
as well as circumferential flow. In addition, pain values were assessed with the
visual analogue scale. Results Mean diffusion in the rostral direction was 9.8 cm
(standard deviation 4.0 cm, range 4.0 to 15.0 cm). Mean diffusion in the caudal
direction was 5.4 cm (standard deviation 1.4 cm, range 3.0 to 8.0 cm). Both
rostral and caudal flow had a p value < 0.001. The circumferential flow was 360
degrees in 9 of 10 cases. In addition, there was significant (p = 0.006)
reduction in pain. Conclusion Interlaminar lumbar epidural steroid injections are
an effective treatment modality for various spine-related conditions. The
injectate diffuses throughout the epidural space with nearly uniform
circumferential flow as well as significant rostral and caudal flow.
PMID- 24353944
TI - Analysis of Relationship between Paraspinal Muscle Fatty Degeneration and
Cervical Spine Motion Using Kinetic Magnetic Resonance Imaging.
AB - The alignment and mobility of the cervical spine is influenced by factors related
to the vertebral bodies, intervertebral discs, ligaments, facet joints, and
muscles. Few reports have described the role played by the paraspinal muscles in
cervical spine mobility. In this study, we investigate the relationship between
fatty degeneration of the paraspinal muscles and cervical motion as assessed with
kinetic magnetic resonance imaging (kMRI). One hundred eighty-eight symptomatic
patients underwent cervical kMRI in neutral, flexion, and extension positions. We
quantified cervical paraspinal muscle fatty infiltration and measured angular
variation and translational motion at each cervical level, and the global Cobb
angle. Cervical paraspinal muscle fatty degeneration demonstrated a pattern in
which C3 and C7 had significantly more fatty infiltration than C4, C5, and C6.
Additionally, when the normal group was compared with the fatty degeneration
group with respect to angular variation, translational motion, and Cobb angle, no
significant differences were found except in angular variation at the C3-C4
level. In conclusion, we found a significantly larger quantity of fatty
degeneration in the paraspinal muscles at C3 and C7 than the middle cervical
levels. Also, we demonstrate that fatty degeneration does not significantly
affect cervical lordotic alignment or mobility characteristics.
PMID- 24353945
TI - Lateral mass fixation in subaxial cervical spine: anatomic review.
AB - Introduction The cervical spine is a highly mobile segment of the spinal column,
liable to a variety of diseases and susceptible to trauma. It is a complex region
where many vital structures lie in close proximity. Lateral mass screw fixation
has become the method of choice in stabilizing subaxial cervical spine among
other posterior cervical fixation techniques whenever the posterior elements are
absent or compromised. Objective This study examined cervical specimens of
cadavers and cervical computed tomography (CT) scans to minimize as much as
possible complications of cervical lateral mass screw placement such as vertebral
artery or nerve root injuries, facet joint violations, or inadequate placement.
Methods Forty normal cervical CT scans, obtained from the emergency unit as part
of the trauma workup, were included in this study plus 10 cervical cadaveric
specimens obtained from the Alexandria Neuro-anatomy laboratory. There were three
fixed parameters for screw insertion in this study. First, the point of screw
insertion was the midpoint of the lateral mass; it was the crossing point between
the sagittal and axial planes of the posterior cortex of the lateral mass.
Second, the direction of the screw in the craniocaudal plane was 30 degrees
cranially to avoid facet joint penetration. Third, the exit point of the screw
was located on the ventral cortex of the lateral mass just lateral to the root of
the transverse process in the midaxial cut of each lateral mass, to make a sound
bicortical fixation without injuring the vertebral artery or the nerve root. The
selected screw trajectory in this study was the line drawn between the inlet and
exit points. The depth and width of the lateral mass of the cervical vertebrae
from C3 to C7 were measured as well as the angle of screw trajectory from the
sagittal plane. All these measures were applied on the cadaveric specimens to
make sure that no injury to the vertebral artery, nerve root, or facet joint
occurred. Results As regards the collected measurements of the lateral mass of
all subaxial cervical vertebrae, the study revealed that the average depth of the
lateral mass was 12.83 +/- 1.28 mm. The average width of the lateral mass was
11.92 +/- 0.96 mm. The average divergent angle of bicortical screw insertion
without injury to the vertebral artery or the nerve root was 19.51 +/- 1.83
degrees. As regard the cadaveric specimens, based on all the collected
measurements taken from the CT scans, there was no reported injury to the
vertebral arteries or nerve roots or penetration to the facet joints. Conclusion
Lateral mass fixation can be applied easily and safely for all levels of subaxial
cervical spine from C3 to C6 with the following parameters: (1) the point of
entry is the midpoint of the lateral mass; (2) the screw trajectory is directed
30 degrees cranially and 20 degrees laterally; (3) the screw length is 13 to 15
mm.
PMID- 24353946
TI - Uncovertebral anatomic midline targeting for cervical disc arthroplasty.
AB - Study Design Prospective observational cohort. Objective To document the accuracy
of uncovertebral anatomic targeting in positioning cervical disc arthroplasty.
Summary of Background Data Disc arthroplasty implants depend on midline placement
for optimum mechanical function. Fluoroscopy is used to delineate the midline.
Anatomic targeting from the uncovertebral joints in the neck may be adequate. We
have investigated the efficacy of uncovertebral anatomic targeting for cervical
disc arthroplasty. Methods Anatomic uncovertebral midline targeting for disc
arthroplasty insertion was performed in 18 male (mean age 51 years, range 27 to
67) and 22 female (mean age 50, range 35 to 70) patients receiving a total of 59
implants over a 5-year period. Device insertion was under only lateral imaging
control. Postinsertion operative fluoroscopy with optimized centering was used to
record implant position in the anteroposterior plane, and centerline analysis was
performed using cursor measurement technology from the GE PACSTM imaging system
(GE Medical Systems, Mt. Prospect, IL). Results Analysis found a mean deviation
from the ideal midline placement of only 0.7 mm (range, 0 to 2.9 mm). Only three
devices were more than 2 mm off the anatomic midline. Conclusion This anatomic
technique is effective, safely minimizing imaging resource needs and X-ray
exposure to the patient and operating team.
PMID- 24353947
TI - Bilateral three-level lumbar spondylolysis repaired by hook-screw technique.
AB - We report a case of bilateral three-level lumbar spondylolysis that was directly
repaired by use of hook-screw technique. The patient complained of low back pain
for 2 years that progressively worsened and was exacerbated with standing and
walking. He also mentioned bilateral sciatalgia. The neurological examination was
normal. Interestingly, we found bilateral lumbar spondylolysis in L3, L4, and L5
levels in imaging studies. After proving that spondylolysis was the source of the
low back pain by local anesthetic agent injection, we used a direct technique for
correction of spondylolysis by use of a hook-screw device plus decortications of
lysis area and iliac crest autograft. We assessed the patient after surgery to
evaluate pain recovery and fusion rate. The results were favorable and proved the
efficacy of the hook-screw technique for treatment of symptomatic multilevel
lumbar spondylolysis.
PMID- 24353948
TI - A Nonenhancing World Health Organization Grade II Intramedullary Spinal
Ependymoma in the Conus: Case Illustration and Review of Imaging Characteristics.
AB - Spinal ependymomas comprise ~60% of all intramedullary tumors in adults.
Ependymomas demonstrate distinct imaging features, such as central location
within the spinal cord, symmetrical expansion, intra- and extratumoral cysts,
hemosiderin caps, and strong enhancement on contrast-injected, T1-weighted
magnetic resonance (MR) imaging. In adults, most ependymomas are myxopapillary,
and in children, most are nonmyxopapillary. In general, nonmyxopapillary or
classic ependymomas are hyperintense on T2- and hypointense on T1-weighted MR
imaging, but whereas the signal intensity on T1 and T2 is variable, homogeneous
contrast enhancement is usually a characteristic finding. Here, the authors
provide an overview on spinal ependymomas with an emphasis on imaging
characteristics and morphological background and present the case of a World
Health Organization grade II ependymoma in the conus that did not enhance.
Interestingly, the tumor contained a large hemorrhagic cyst. Just as hemorrhagic
metastatic tumors may not enhance, a hemorrhagic ependymoma may likewise not
enhance after administration of contrast agent. Thus, the differential diagnosis
of a nonenhancing intramedullary lesion in the conus should include ependymoma,
particularly if there is concomitant hemorrhage.
PMID- 24353949
TI - Thoracic hyperkyphosis: assessment of the distal fusion level.
AB - Study Design This is a retrospective study. Objective The objective of this study
was to assess the sagittal stable vertebra (SSV) versus the first lordotic
vertebra (FLV) as the inferior fusion level in patients undergoing spinal surgery
for thoracic hyperkyphosis. The main outcome of interest was the development of
distal junctional kyphosis (DJK). Summary of Background Data Prior research has
pointed to selection of the FLV for the distal instrumentation level in fusion
for thoracic hyperkyphosis. In 2009, Cho et al introduced the concept of the SSV
after recognizing the development of DJK despite fusion to the FLV. Methods
Patients were reviewed who had undergone spinal fusion for thoracic
hyperkyphosis. Preoperative radiographs were reviewed to assess thoracic
kyphosis, lumbar lordosis, SSV, and FLV. Postoperative radiographs were reviewed
to assess curve correction and whether patients developed DJK or implant failure.
Results We reviewed 22 patients with a mean age at surgery of 18 (range 14 to
22). Mean preoperative kyphosis was 85 +/- 14 degrees, and mean postoperative
kyphosis at final follow-up was 59 +/- 12 degrees for a mean correction of 26 +/-
12 degrees. Eleven patients developed DJK and four patients experienced hardware
failure. In 12 patients, the SSV was inferior to the FLV. Rates of DJK when the
instrumentation included the SSV or FLV were 13 and 38%, respectively.
Conclusions Fusion to the SSV is superior at preventing DJK when compared with
fusion to the FLV.
PMID- 24353950
TI - Inception of an Australian spine trauma registry: the minimum dataset.
AB - Background The establishment of a spine trauma registry collecting both spine
column and spinal cord data should improve the evidential basis for clinical
decisions. This is a report on the pilot of a spine trauma registry including
development of a minimum dataset. Methods A minimum dataset consisting of 56 data
items was created using the modified Delphi technique. A pilot study was
performed on 104 consecutive spine trauma patients recruited by the Victorian
Orthopaedic Trauma Outcomes Registry (VOTOR). Data analysis and collection
methodology were reviewed to determine its feasibility. Results Minimum dataset
collection aided by a dataset dictionary was uncomplicated (average of 5 minutes
per patient). Data analysis revealed three significant findings: (1) a peak in
the 40 to 60 years age group; (2) premorbid functional independence in the
majority of patients; and (3) significant proportion being on antiplatelet or
anticoagulation medications. Of the 141 traumatic spine fractures, the
thoracolumbar segment was the most frequent site of injury. Most were
neurologically intact (89%). Our study group had satisfactory 6-month patient
reported outcomes. Conclusion The minimum dataset had high completion rates, was
practical and feasible to collect. This pilot study is the basis for the
development of a spine trauma registry at the Level 1 trauma center.
PMID- 24353951
TI - Segmental stiffness achieved by three types of fixation for unstable lumbar
spondylolytic motion segments.
AB - Objective The objective of this study was to compare the relative stability in
lumbar spondylolysis (SP) of a rigid anterior plate (with a novel compression
slot) versus traditional posterior pedicle screw (PS) fixation. Summary of
Background Data Arthrodesis has been a mainstay of treatment for symptomatic
isthmic spondylolisthesis in adults. Posterior PS fixation has become a commonly
used adjunct. Some have advocated anterior lumbar interbody fixation (ALIF) plate
as an alternative. The relative stability afforded by ALIF in SP has not been
well characterized, nor has the contribution afforded by a compression screw slot
in an ALIF plate. Methods Calf spine segments were characterized in the normal
state, after sectioning the pars (SP model), then after reconstruction with an
interbody spacer and either PS/rods, or an ALIF plate, or both. Results ALIF
plate conferred stability on the spondylolytic segment only comparable to that of
the normal functional spinal unit (FSU). Posterior fixation was more stable than
anterior fixation in all testing modes. Addition of an ALIF plate conferred a
significant additional stability in those that already had posterior fixation.
The utilization of an anterior compression screw conferred additional stability
in extension testing only. Conclusions ALIF plate reconstruction in the setting
of SP may not confer enough segmental stability to predictably encourage fusion
beyond that of the uninstrumented intact FSU. The utilization of an integral
compression screw in an ALIF plate may not confer clinically significant
additional construct stability in SP.
PMID- 24353952
TI - Microendoscopic Decompression Surgery for Lumbar Spinal Canal Stenosis via the
Paramedian Approach: Preliminary Results.
AB - The objective of this study was to evaluate the efficacy of a microendoscopic
spinal decompression surgical technique using a novel approach for the treatment
of lumbar spinal canal stenosis (LSCS). The following modifications were made to
the conventional microendoscopic bilateral decompression via the unilateral
approach: the base of the spinous process was first resected partially to secure
a working space, so as not to separate the spinous process from the lamina. The
tip of the tubular retractor was placed at the midline of the lamina, where
laminectomy was performed microendoscopically. A total of 126 stenotic levels
were decompressed in 70 patients. The mean operating time per level was 77.0
minutes, and the mean intraoperative blood loss per level was 15.0 mL. There were
no dural tears or neurological injuries intraoperatively. Fracture of the spinous
process was detected postoperatively in two patients, both of whom were
asymptomatic. All patients could be followed up for at least 12 months. Their
median Japanese Orthopaedic Association (JOA) score improved significantly from
16 points preoperatively to 27.5 points after the surgery (p < 0.001). The case
series showed that the modifications of the technique improved the safety and
ease of performance of the microendoscopic decompression surgery for LSCS.
PMID- 24353953
TI - Comparison of Three-Dimensional Fluoroscopy versus Postoperative Computed
Tomography for the Assessment of Accurate Screw Placement after Instrumented
Spine Surgery.
AB - While intraoperative three-dimensional fluoroscopy does not possess the
resolution and image quality of computed tomography (CT), it may provide adequate
information about screw placement to guide intra- and postoperative decision
making. We compared the accuracy of intraoperative three-dimensional fluoroscopy
visualization of proper screw placement with that of postoperative CT. We
retrospectively reviewed spinal instrumentation procedures done using the O-arm
(Medtronic, Minneapolis, MN, USA) that also had postoperative CT. All screws were
assessed for placement accuracy on O-arm and CT images on a 4-point scale. In
this study, 20 cases met the inclusion criteria. Thirteen breaches (11 grade 1
and 2 grade 2) were identified on O-arm images, and 14 breaches (10 grade 1, 3
grade 2, and 1 grade 3) were identified on CT. Sensitivity, specificity, and
positive and negative predictive values were 93, 99, 99, and 98%, respectively.
The Kappa value (0.96) suggested a very high degree of agreement between three
dimensional fluoroscopy and CT in determining accuracy of screw placement. These
findings may allow less frequent use of postoperative CT scans, improving cost
effectiveness in patients who require spinal instrumentation procedures and
potentially decreasing the number of patients who require replacement of an
inappropriately positioned screw.
PMID- 24353954
TI - The incidence of bifid c7 spinous processes.
AB - For posterior cervical surgery, if the operation only involves the lower cervical
area, counting from C2 is impractical and the level may not be visible on X-rays.
In such cases, we usually place a marker at the top of the incision and also rely
on the size and monofid shape of the C7 spinous process. Relying on the C7
morphology, however, we initially instrumented the wrong levels in a case where
the patient had a bifid C7 spinous process. We therefore sought to determine the
frequency of bifid cervicothoracic spinous processes. Computed tomography axial
images of C6, C7, and T1 from 516 patients were evaluated. The spinous processes
were classified into three categories: "bifid," "partially bifid," and "monofid."
C6 spinous process was monofid in 47.9% of cases, partially bifid in 4.2% of
cases, and bifid in 47.9% of cases. C7 spinous process was monofid in 99.2% of
cases, partially bifid in 0.5% of cases, and bifid in 0.3% of cases. T1 was
monofid in all cases. A truly bifid C7 spinous process occurs 0.3% of the time
and therefore is not a reliable landmark for choosing fusion levels. This
knowledge hopefully helps prevent the type of wrong-level instrumentation that we
performed.
PMID- 24353955
TI - Cervical total disc arthroplasty.
AB - Symptomatic adjacent segment degeneration of the cervical spine remains
problematic for patients and surgeons alike. Despite advances in surgical
techniques and instrumentation, the solution remains elusive. Spurred by the
success of total joint arthroplasty in hips and knees, surgeons and industry have
turned to motion preservation devices in the cervical spine. By preserving motion
at the diseased level, the hope is that adjacent segment degeneration can be
prevented. Multiple cervical disc arthroplasty devices have come onto the market
and completed Food and Drug Administration Investigational Device Exemption
trials. Though some of the early results demonstrate equivalency of arthroplasty
to fusion, compelling evidence of benefits in terms of symptomatic adjacent
segment degeneration are lacking. In addition, non-industry-sponsored studies
indicate that these devices are equivalent to fusion in terms of adjacent segment
degeneration. Longer-term studies will eventually provide the definitive answer.
PMID- 24353956
TI - Symptomatic lumbar disc protrusion causing progressive myelopathy in a low-lying
cord.
AB - Low-lying cord is an uncommon entity, and cord compression due lumbar disc
disease is rarely encountered. We discuss our experience with a case of lumbar
cord compression secondary to a large disc protrusion, which caused myelopathy in
a low-lying/tethered cord. A 77-year-old woman with known spina bifida occulta
presented with 6-week history of severe low back pain and progressive
paraparesis. Magnetic resonance imaging showed a low-lying tethered cord and a
large disc prolapse at L2/3 causing cord compression with associated
syringomyelia. Medical comorbidities precluded her from anterior decompression,
and therefore a posterior decompression was performed. She recovered full motor
power in her lower limbs and could eventually walk unaided. She had a deep wound
infection, which was successfully treated with debridement, negative pressure
therapy (vacuum-assisted closure pump), and antibiotics. Six months after
surgery, her Oswestry Disability Index improved from 55% preoperatively to 20%.
Posterior spinal cord decompression for this condition has been successful in our
case, and we believe that the lumbar lordosis may have helped indirectly
decompress the spinal cord by posterior decompression alone.
PMID- 24353957
TI - High-grade adult isthmic L5-s1 spondylolisthesis: a report of intraoperative slip
progression treated with surgical reduction and posterior instrumented fusion.
AB - Adult isthmic spondylolisthesis most commonly occurs at the L5-S1 level of the
lumbar spine. Slip progression is relatively rare in adults with this condition
and slippage is typically associated with advanced degeneration of the disk below
the pars defect. When symptomatic, radiculopathy is the typical complaint in
adults with isthmic spondylolisthesis. When considering options for surgical
treatment of adult isthmic spondylolisthesis, the surgeon must consider several
different options, such as decompression, fusion, instrumentation, reduction, and
type of bone graft to be used. All of these decisions must be individualized as
deemed appropriate for each particular patient. This report presents a case of
intraoperative slip progression of a L5-S1 adult isthmic spondylolisthesis to a
high-grade slip, which was treated with complete surgical reduction and posterior
instrumented fusion. This case demonstrates the potential instability of this
condition in adults and has not been previously reported. The case details and
images are reviewed and the intraoperative decisions, treatment options, and
patient outcome are discussed.
PMID- 24353958
TI - Surgical outcome for foot drop in lumbar degenerative disease.
AB - Controversy exists regarding the timing and outcome of surgery for lumbar
degenerative disease (LDD) associated with foot drop. In this work, we report the
results of a retrospective observational study from our center. We had a sample
size of 26 patients with a minimum follow-up of 6 months. Of the 26 patients, 88%
improved, with complete recovery observed in 61%. Thus, our data support the view
that there is good recovery from operative management of foot drop secondary to
LDD. Adjusting for preoperative strength, preoperative duration of weakness was a
significant predictor of extent of recovery (odds ratio = 0.93; 95% confidence
interval 0.88 to 0.98; p = 0.019). The model explained 50% of the variance in
outcome in this study.
PMID- 24353959
TI - Histomorphometric analysis of experimental disc degeneration.
AB - Symptomatic disc degeneration is a complex pathological condition that involves a
cascade of events and is not totally understood. In this context, animal models
gain an important role, allowing for better understanding of the degenerative
process and therapeutic interventions. There are several models with different
methods of evaluation of experimental disc degeneration (EDD), including imaging,
biochemical, genetics, and histological approaches, but no real gold standard has
been set. The authors aim to evaluate EDD by means of automated morphometric
analysis and to determine values for differentiating normal and degenerated discs
by this method. The criteria mean and total cellular area, mean and total
cytoplasm area, and total nuclear area of cells in the nucleus pulposus were able
to differentiate the condition of degeneration (p < 0.05). In conclusion, by
applying the histomorphometric analysis of EDD, the authors could present an
objective measure of EDD changes within the nucleus pulposus, reducing the
evaluator bias in future studies and presenting highly sensitive and specific
criteria for EDD.
PMID- 24353960
TI - Radiation Therapy without Surgery for Spinal Metastases: Clinical Outcome and
Prognostic Factors Analysis for Pain Control.
AB - The purpose of radiation therapy (RT) for patients with spinal metastases is pain
relief and control of paralysis. The aim of the present study was to assess pain
relief using RT and to evaluate prognostic factors for pain control. We evaluated
97 consecutive patients, of mean age 62.7 years (range 28 to 86), with spinal
metastases that had been treated by RT. We evaluated the effects of RT using pain
level assessed using a drug grading scale based on the World Health Organization
standards. The following potential prognostic factors for pain control of RT were
evaluated using multivariate logistic regression analysis: age, gender, tumor
type, performance status (PS), number of spinal metastases, and a history of
chemotherapy. Among the 97 patients who underwent RT for pain relief, 68 patients
(70.1%) presented with pain reduction. PS (odds ratio: 1.931; 95% confidence
interval: 1.244 to 2.980) was revealed by multivariate logistic regression
analysis to be the most important prognostic factor for pain control using RT. In
conclusion, we found that RT was more effective for patients with spinal
metastases while they maintained their PS.
PMID- 24353961
TI - Screw placement accuracy for minimally invasive transforaminal lumbar interbody
fusion surgery: a study on 3-d neuronavigation-guided surgery.
AB - Purpose The aim of this study was to assess the impact of 3-D navigation for
pedicle screw placement accuracy in minimally invasive transverse lumbar
interbody fusion (MIS-TLIF). Methods A retrospective review of 52 patients who
had MIS-TLIF assisted with 3D navigation is presented. Clinical outcomes were
assessed with the Oswestry Disability Index (ODI), Visual Analog Scales (VAS),
and MacNab scores. Radiographic outcomes were assessed using X-rays and thin
slice computed tomography. Result The mean age was 56.5 years, and 172 screws
were implanted with 16 pedicle breaches (91.0% accuracy rate). Radiographic
fusion rate at a mean follow-up of 15.6 months was 87.23%. No revision surgeries
were required. The mean improvement in the VAS back pain, VAS leg pain, and ODI
at 11.3 months follow-up was 4.3, 4.5, and 26.8 points, respectively. At last
follow-up the mean postoperative disc height gain was 4.92 mm and the mean
postoperative disc angle gain was 2.79 degrees. At L5-S1 level, there was a
significant correlation between a greater disc space height gain and a lower VAS
leg score. Conclusion Our data support that application of 3-D navigation in MIS
TLIF is associated with a high level of accuracy in the pedicle screw placement.
PMID- 24353962
TI - Nicotine Increases Osteoblast Activity of Induced Bone Marrow Stromal Cells in a
Dose-Dependent Manner: An in vitro Cell Culture Experiment.
AB - Previous studies by our group showed that nicotine delivered via a transdermal
nicotine patch significantly enhanced posterior spinal fusion rates in rabbits.
Nicotine transdermal patches provide a steady serum level; there may be a dose
dependent effect of nicotine on posterior spinal fusion. In an in vitro cell
culture model of rabbit bone marrow-derived osteoblast-like cells, cells were
exposed to different concentrations of nicotine (0, 20, 40, 80 ng/mL and 10, 100,
250 MUg/mL). Wells were stained with an alkaline phosphatase (ALP) staining kit
to determine ALP enzyme activity. Cells were stained with Von Kossa for
mineralization. A two-way analysis of variance (ANOVA) using dose and time as
variables showed significant differences among groups; post hoc analysis showed
that the 100-MUg/mL dose of nicotine significantly enhanced ALP activity over
controls. A one-way ANOVA using dose as the variable showed that the 100- and 250
MUg/mL doses had significantly greater mineralization than controls. Dose
response analysis revealed a statistically significant effect of nicotine dose on
ALP activity and Von Kossa activity. The effects of nicotine on spinal fusion may
be dose-dependent and due to stimulation of osteoblastic activity. Nicotine may
not be responsible for the inhibited bone healing observed in smokers.
PMID- 24353963
TI - Acute Schmorl's Node during Strenuous Monofin Swimming: A Case Report and Review
of the Literature.
AB - Study Design This case report describes an acute Schmorl's node (SN) in an elite
monofin athlete during exercise. The patient presented with severe back pain and
leg numbness and was managed successfully with conservative treatment. Objective
The aim of our communication was to describe a rare presentation of a common
pathological condition during an intense sport. Background Swimming is not
generally considered to be a sport activity that leads to spinal injuries. SNs
are usually asymptomatic lesions, incidentally found on imaging studies. There is
no correlation between swimming and symptomatic SN formation. Case Report A 16
year-old monofin elite athlete suffered from an acute nonradiating back pain
during extreme exercise. His back pain was associated with a fracture of the
superior L5 end plate and an acute SN at the L5 vertebral body with perilesional
bone marrow edema. The pain resolved with nonsteroidal anti-inflammatory drugs
and bed rest. The athlete had an excellent outcome and returned to his training
activities 6 months after his incident. Conclusion SN should be considered in the
differential diagnosis of severe back pain, especially in sport-related injuries.
SNs present with characteristic imaging findings. Due to the benign nature of
these lesions, surveillance-only management may be the best course of action.
PMID- 24353964
TI - Preoperative sclerotherapy using sodium tetradecyl sulphate (fibro-veinTM) can
assist in the management of vertebral hemangiomas.
AB - Vertebral hemangiomas are benign lesions accounting for 2 to 3% of all spinal
tumors. They are usually asymptomatic and found incidentally on imaging.
Uncommonly, vertebral hemangiomas with significant epidural extension can result
in radiculopathy or spinal cord compression. Decompressive surgery with or
without stabilization is often required when neurological deficits are present.
However, surgery can be associated with massive hemorrhage as these tumors are
hypervascular. Preoperative embolization and sclerotherapy are well-known
management strategies used to minimize intraoperative bleeding and improve
symptoms. Recently, the use of sclerosants such as ethanol has decreased, due to
reported complications such as Brown-Sequard syndrome. We describe the use of
sodium tetradecyl sulfate (Fibro-VeinTM, STD Pharmaceutical, Hereford, UK) as an
effective alternative to ethanol in the preoperative management of vertebral
hemangiomas. To our knowledge, this has not been previously reported. In three
patients, we demonstrated minimal intraoperative blood loss using a combination
of preoperative embolization of arterial feeders and sclerotherapy with sodium
tetradecyl sulfate to control and secure venous drainage. No patients developed
complications related to the procedure. In addition to minimal blood loss, a
clear dissection plane was also noted intraoperatively.
PMID- 24353965
TI - Thoracic aortic dissection and mycotic pseudoaneurysm in the setting of an
unstable upper thoracic type b2 fracture.
AB - Thoracic type B2 fractures are high-energy injuries. It is crucial to maintain a
high index of suspicion for concomitant visceral injuries. A 33-year-old man
presented after a motor vehicle accident with a T4 type B2.3 fracture with an
associated sternum fracture. He was treated with a T4 corpectomy and an
expandable titanium cage and lateral plate construct at T3-T5. Two months later
he developed focal kyphosis and loosening of his screws. This was addressed with
an instrumented posterior fusion from T1 to T8 complicated by a wound infection,
pneumonia, and fungal esophagitis requiring several debridements and vacuum
assisted closure therapy. Worsening back pain prompted a thoracic computed
tomography scan, revealing a dissecting thoracic-aortic aneurysm, which was
treated with an endovascular stent graft. Few months later, he presented with
fevers, chills, and hemoptysis secondary to Staphylococcus aureus bacteremia,
endovascular leak, and T3-T5 osteomyelitis. He was transferred to our institution
and restented by the cardiothoracic service. Subsequently, he underwent a
thoracotomy, evacuation of infected aneurysmal hematoma with removal of
instrumentation. A revision corpectomy with iliac crest autograft reconstruction
was performed without complications. The patient's infection and thoracic pain
resolved. However, there was a significant delay in treatment, resulting in
substantial morbidity. Patients with thoracic type B2 fractures require careful
evaluation for concomitant aortic and visceral injuries. Missed associated
injuries result in increased morbidity and mortality.
PMID- 24353966
TI - Total disc arthroplasty and anterior cervical discectomy and fusion in cervical
spine: competitive or complimentary? Review of the literature.
AB - Anterior cervical discectomy and arthrodesis has come to represent standard of
care for patients with persistent radicular and/or myelopathic symptoms that have
failed to improve with conservative treatments. One potential complication of the
procedure is the accelerated degeneration of the vertebrae and the intervertebral
discs adjacent to the level fused and the effects of fusion on those levels. The
concern that fusion may be a contributing factor to accelerated adjacent segment
degeneration led to increased interest in cervical disc replacement after
anterior decompressive surgery. Several studies analyzing the short-term outcomes
of the disc replacement procedure have been published since then, and the pros
and cons of both procedures continue to remain a topic of debate among the
scientific community. The analysis of published literature and our own experience
has convinced us that the overall longer-term clinical outcomes after anterior
cervical discectomy and fusion (ACDF) and total disc replacement (TDR) in the
general patient population are not significantly different in terms of
symptomatic improvement, neurological improvement, and restoration to better
quality of life. Age of the patients and number of affected levels may impact the
outcomes and hence determine the choice of optimum procedure. To definitely
compare the incidence of adjacent segment disease after these procedures, multi
institutional studies with predetermined and unanimously agreed upon clinical and
radiological criteria should be undertaken and the results analyzed in an
unbiased fashion. Until that time, it is reasonable to assume that ACDF as well
as cervical TDR are both safe and effective procedures that may have outcome
benefits in specific patient subgroups based upon demographics and
clinical/radiological parameters at the time of surgery.
PMID- 24353967
TI - Laminoplasty for cervical myelopathy.
AB - This article reviews cervical laminoplasty. The origin of cervical laminoplasty
dates back to cervical laminectomy performed in Japan ~50 years ago. To overcome
poor surgical outcomes of cervical laminectomy, many Japanese orthopedic spine
surgeons devoted their lives to developing better posterior decompression
procedures for the cervical spine. Thanks to the development of a high-speed
surgical burr, posterior decompression procedures for the cervical spine showed
vast improvement from the 1970s to the 1980s, and the original form of cervical
laminoplasty was determined. Since around 2000, surgeons performing cervical
laminoplasty have been adopting less invasive procedures for the posterior
cervical muscle structures so as to minimize postoperative axial neck pain and
obtain better functional outcomes of the cervical spine. This article covers the
history of cervical laminoplasty, surgical procedures, the benefits and
limitation of this procedure, and surgery-related complications.
PMID- 24353968
TI - A radiological comparison of anterior fusion rates in anterior lumbar interbody
fusion.
AB - Aim To compare anterior fusion in standalone anterior lumbar interbody fusion
(ALIF) using cage and screw constructs and anterior cage-alone constructs with
posterior pedicle screw supplementation but without posterior fusion. Methods
Eighty-five patients underwent single- or two-level ALIF procedure for
degenerative disk disease or lytic spondylolisthesis (SPL). Posterior
instrumentation was performed without posterior fusion in all cases of lytic SPL
and when the anterior cage used did not have anterior screw through cage
fixation. Results Seventy (82%) patients had adequate radiological follow-up at a
mean of 19 months. Forty patients had anterior surgery alone (24 single level and
16 two levels) and 30 had front-back surgery (15 single level and 15 two levels).
Anterior locked pseudarthrosis was only seen in the anterior surgery-alone group
when using the STALIF cage (Surgicraft, Worcestershire, UK) (37 patients). This
occurred in five of the single-level surgeries (5/22) and nine of the two-level
surgeries (9/15). Fusion was achieved in 100% of the front-back group and only
65% (26/40) of the anterior surgery-alone group. Conclusion Posterior pedicle
screw supplementation without posterolateral fusion improves the fusion rate of
ALIF when using anterior cage and screw constructs. We would recommend
supplementary posterior fixation especially in cases where more than one level is
being operated.
PMID- 24353969
TI - Concurrent tethered cord release and growing-rod implantation-is it safe?
AB - Study Design Retrospective case series from one institution with a comparison
control group. Objective To evaluate the safety of concomitant tethered cord
release and growing-rod insertion in individuals with early onset scoliosis.
Methods We retrospectively reviewed patients who underwent concurrent tethered
cord release and growing-rod insertion. We compared our data to a comparison
control group of eight patients who underwent staged tethered cord release and
growing-rod insertion. Results We identified three patients meeting criteria.
There were no neurological complications in the three patients who underwent
concomitant surgery. Average immediate postoperative curve correction was 43.3
degrees (47.6%). We identified seven patients who underwent staged surgery from a
multicenter prospective database. No neurological complications were reported,
and average immediate postoperative correction was 35.1 degrees (46.2%).
Conclusion We believe that concurrent tethered cord release and growing-rod
insertion can be performed safely with the use of multimodality
neurophysiological monitoring techniques.
PMID- 24353970
TI - Construct Rigidity after Fatigue Loading in Pedicle Subtraction Osteotomy with or
without Adjacent Interbody Structural Cages.
AB - Introduction Studies document rod fracture in pedicle subtraction osteotomy (PSO)
settings where disk spaces were preserved above or adjacent to the PSO. This
study compares the multidirectional bending rigidity and fatigue life of PSO
segments with or without interbody support. Methods Twelve specimens received
bilateral T12-S1 posterior fixation and L3 PSO. Six received extreme lateral
interbody fusion (XLIF) cages in addition to PSO at L2-L3 and L3-L4; six had PSO
only. Flexion-extension, lateral bending, and axial rotation (AR) tests were
conducted up to 7.5 Newton-meters (Nm) for groups: (1) posterior fixation, (2) L3
PSO, (3) addition of cages (six specimens). Relative motion across the osteotomy
(L2-L4) and entire fixation site (T12-S1) was measured. All specimens were then
fatigue tested for 35K cycles. Results Regardingmultiaxial bending, there was a
significant 25.7% reduction in AR range of motion across L2-L4 following addition
of cages. Regarding fatigue bending, dynamic stiffness, though not significant (p
= 0.095), was 22.2% greater in the PSO + XLIF group than in the PSO-only group.
Conclusions Results suggest that placement of interbody cages in PSO settings has
a potential stabilizing effect, which is modestly evident in the acute setting.
Inserting cages in a second-stage surgery remains a viable option and may benefit
patients in terms of recovery but additional clinical studies are necessary to
confirm this.
PMID- 24353971
TI - Surgical outcomes of osteoporotic vertebral collapse: a retrospective study of
anterior spinal fusion and pedicle subtraction osteotomy.
AB - The purpose of this retrospective study was to demonstrate the surgical outcomes
of anterior spinal fusion (ASF) and posterior subtraction osteotomy (PSO) for
osteoporotic vertebral collapse (OVC). Forty patients who underwent surgery for
OVC at the thoracolumbar junction with neurological deficits were included in
this study. ASF was primarily chosen for patients without vertebral compression
fracture at other levels, and PSO was chosen for patients with more severe
kyphosis or with multiple vertebral fractures. ASF was performed in 26 patients
and PSO was performed in 14 patients. We evaluated the pre- and postoperative
clinical status consisting of pain, gait, paralysis, and bladder function
analysis. Additionally, pre- and postoperative kyphosis, correction angle,
correction loss, and upright balance were investigated radiologically.
Improvements in pain level, gait, paralysis, and bladder function were obtained
in both groups. Average correction angles in the ASF and PSO groups were 16 and
37, respectively. Average correction losses at the final follow-up in the ASF and
PSO groups were 7 and 13, respectively. Newly developed postsurgical vertebral
compression fracture adjacent to the level of instrumentation was observed in
four patients (15%) in the ASF group and in 11 patients (79%) from the PSO group.
ASF provided satisfactory outcomes for patients with thoracolumbar OVC, who have
no vertebral compression fracture at other levels. Although PSO has benefits for
the correction of kyphosis, several problems persist with this procedure,
especially for patients with severe osteoporosis.
PMID- 24353972
TI - Charcot arthropathy of the wrist associated with cervical spondylotic myelopathy.
AB - Background Charcot arthropathy is a cascade of destructive changes that can
effect joints of both the axial and appendicular skeleton. The pathogenesis of
this condition centers around the accumulation of minor traumatic events after
the loss of normal joint sensation. The most frequently cited cause of Charcot
arthropathy of the upper extremity is syringomyelia, and magnetic resonance
imaging of the cervical spine should be obtained at presentation. Case Report A
72-year-old woman presented with a painless right wrist deformity. Radiographs
demonstrated advanced destructive changes of the radiocarpal joint. Magnetic
resonance imaging of the cervical spine revealed multilevel cervical spondylotic
stenosis with cord deformation, but no evidence of syringomyelia. Neurological
examination confirmed the presence of myelopathy. Literature Review The most
frequently cited cause of Charcot arthropathy of the upper extremity is
syringomyelia, although pathologies such as diabetes mellitus, tabes dorsalis,
leprosy, and other disorders affecting the nervous system have been reported to
lead to this condition. Neuropathic arthropathy involving the wrist is a rare
phenomenon with fewer than 20 published reports in modern literature. Clinical
Relevance Charcot arthropathy of the wrist is a rare but potentially disabling
condition. The diagnosis of spondylotic myelopathy should be considered when
evaluating a patient with this presentation. Evaluation consisting of a detailed
neurological examination and advanced imaging of the cervical spine is warranted
to identify the etiology.
PMID- 24353973
TI - Methicillin-Resistant Staphylococcus aureus Vertebral Osteomyelitis Following
Epidural Catheterization: A Case Report and Literature Review.
AB - Indwelling epidural catheters are frequently used to manage postoperative pain.
This report describes a patient who developed methicillin-resistant
Staphylococcus aureus (MRSA) vertebral osteomyelitis of the lumbar spine
following epidural catheterization. To the best of our knowledge, this is the
first reported case of MRSA vertebral osteomyelitis secondary to epidural
catheter use in the English orthopedic literature. The patient and his family
consented to publishing the data.
PMID- 24353974
TI - Traumatic posterior L4-L5 fracture dislocation of the lumbar spine: a case
report.
AB - Study Design Case report. Objective The diagnosis and surgical management of a
patient with traumatic bilateral posterior dislocation of L4-L5 is presented with
a thorough review of the existing literature. Summary of Background Data
Traumatic dislocation of L4-L5 has been reported in the English literature in
only five cases; of these, only two were retrolisthesis. Methods A 20-year-old
patient was involved in a high-energy vehicular accident and presented with back
pain and inability to ambulate. Neurological assessment showed motor strength
grade 2/5 in the proximal lower-extremity muscle groups (L1-L3 myotomes) and 0/5
strength distally (L4-S1 myotomes); in addition, incontinence of sphincters was
found. X-rays and computed tomography (CT) scan revealed a three-column
ligamentous injury with posterior fracture-dislocation of the L4 vertebral body
with complete posterior displacement of L4 to L5 vertebral body. The patient
underwent posterior approach with reduction, transpedicular fixation, and
posterolateral fusion with autologous bone graft. Results At 1-year follow-up,
the patient had recovered muscular strength in proximal lower-extremities muscle
groups, sphincter function had fully recovered, and he was able to ambulate with
crutches. There was no recovery of distal extremity sensorimotor function. Plain
radiograph and CT scan showed good alignment and progressive maturation of his
fusion procedure. Conclusion Traumatic retrolisthesis of L4-L5 is a high-energy
unstable fracture; reduction of the dislocation is challenging because of the
heavy forces acting in the lower lumbar spine. Instrumented fusion restores
alignment and maintains segmental stability.
PMID- 24353975
TI - Improving the clinical evidence of bone graft substitute technology in lumbar
spine surgery.
AB - Bone graft substitutes have been used routinely for spine fusion for decades, yet
clinical evidence establishing comparative data remains sparse. With recent
scrutiny paid to the outcomes, complications, and costs associated with
osteobiologics, a need to improve available data guiding efficacious use exists.
We review the currently available clinical literature, studying the outcomes of
various biologics in posterolateral lumbar spine fusion, and establish the need
for a multicenter, independent osteobiologics registry.
PMID- 24353976
TI - Strategy in the surgical treatment of primary spinal tumors.
AB - Primary spine tumors are rare, accounting for only 4% of all tumors of the spine.
A minority of the more common primary benign lesions will require surgical
treatment, and most amenable malignant lesions will proceed to attempted
resection. The rarity of malignant primary lesions has resulted in a paucity of
historical data regarding optimal surgical and adjuvant treatment and, although
we now derive benefit from standardized guidelines of overall care, management of
each neoplasm often proceeds on a case-by-case basis, taking into account the
individual characteristics of patient operability, tumor resectability, and
biological potential. This article aims to provide an overview of diagnostic
techniques, staging algorithms and the authors' experience of surgical treatment
alternatives that have been employed in the care of selected benign and malignant
lesions. Although broadly a review of contemporary management, it is hoped that
the case illustrations given will serve as additional "arrows in the quiver" of
the treating surgeon.
PMID- 24353977
TI - Therapeutic effects of sesame oil on monosodium urate crystal-induced acute
inflammatory response in rats.
AB - Sesame oil has been used in traditional Taiwanese medicine to relieve the
inflammatory pain in people with joint inflammation, toothache, scrapes, and
cuts. However, scientific evidence related to the effectiveness or action
mechanism of sesame oil on relief of pain and inflammation has not been examined
experimentally. Here, we investigated the therapeutic effect of sesame oil on
monosodium urate monohydrate (MSU) crystal-induced acute inflammatory response in
rats. Air pouch, a pseudosynovial cavity, was established by injecting 24 mL of
filtered sterile air subcutaneously in the backs of the rats. At day 0,
inflammation in air pouch was induced by injecting MSU crystal (5 mg/rat,
suspended in sterilized phosphate buffered saline, pH 7.4), while sesame oil (0,
1, 2, or 4 mL/kg, orally) was given 6 h after MSU crystal injection. Parameters
in lavage and skin tissue from the air pouches were assessed 6 h after sesame oil
was given. Sesame oil decreased MSU crystal-induced total cell counts, tumor
necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 levels in lavage and
pouch tissue. Sesame oil significantly decreased leukocyte and neutrophil counts
in lavage compared with MSU crystal alone group. Sesame oil decreased activated
mast cell counts in skin tissue in MSU crystal-treated rats. Sesame oil
significantly decreased nuclear factor (NF)-kappaB activity and IL-4 level in
isolated mast cells from rats treated with MSU crystal. Furthermore, sesame oil
decreased lavage complement proteins C3a and C5a levels in MSU crystal-treated
rats. In conclusion, sesame oil shows a potent therapeutic effect against MSU
crystal-induced acute inflammatory response in rats.
PMID- 24353978
TI - Epicatechin-induced conformational changes in beta-lactoglobulin B monitored by
FT-IR spectroscopy.
AB - ABSTRACT: The interaction between whey carrier protein beta-lactoglobulin B and (
)-epicatechin, a major dietary flavonoid with a wide range of health-promoting
biological activities, was investigated by Fourier transform infrared
spectroscopy in physiological conditions. Amide I spectra of epicatechin - beta
lactoglobulin complexes, in D2O buffer solutions, pD= 6.8, at molar ratios from
0.5:1 to 15:1, were measured by using a cell device specifically created. Changes
in secondary structure elements at increasing epicatechin concentrations were
quantified. Two different trends were observed for the intensities of beta-sheet,
random coil, and side chain contributions. At molar ratios <=2 the beta-exposed
strand contributions (1625 cm(-1)) increased at the expence of the beta
antiparallel sheet band (1637 cm(-1)). At molar ratios >2 the intensities of both
beta structures slightly decreased. The same behaviour was observed for the side
chain contributions (band around 1610 / 1620 cm(-1)). In addition, a
conformational transition to a slightly opened structure, followed by aggregate
formation at the highest molar ratios, were revealed. The results suggest that
binding of epicatechin to beta-lactoglobulin in physiological conditions occurs
at the surface of the protein molecule, resulting in protein dissociation at
molar ratios <=2 with minor changes in secondary structure. This finding provides
further evidence for the possibility of successful use of the protein as a
carrier of flavonoids, epicatechin included.
PMID- 24353980
TI - Feasibility of resuscitation contrast-enhanced postmortem computed tomography
using cardiopulmonary resuscitation technique with chest compression immediately
after death.
AB - PURPOSE: Our purpose was to evaluate image delineation ability of contrast
enhanced post-mortem computed tomography (CEPMCT) using cardiopulmonary
resuscitation technique of chest compression, named "resuscitation CEPMCT".
MATERIALS AND METHODS: Non-traumatically-deceased 15 subjects (7 men; 8 women)
aged 19-87 years (mean 61 years) underwent resuscitation CEPMCT. The contrast
enhanced technique, while injecting 100 ml of contrast media from the right
cubital vein at a rate of 1 ml/s, chest compression was performed for 2 minutes
at a rate of 100 times/min (a total of 200 times). CT attenuation values
(Hounsfield Unit: HU) were measured in 8 target vessels: 1) pulmonary artery, 2)
coronary artery, 3) ascending aorta, 4) abdominal aorta, 5) celiac trunk, 6)
common iliac artery, 7) superior vena cava, and 8) inferior vena cava. One-sided
Student's t-test was performed to assess whether measured values were higher than
140 HU by setting p-value at 0.05. RESULTS: Measured CT values in the 8 vessels
were 1) pulmonary artery: 325 +/- 140 HU, 2) coronary artery: 240 +/- 73 HU, 3)
ascending aorta: 321 +/- 127 HU, 4) abdominal aorta: 286 +/- 96 HU, 5) celiac
trunk: 233 +/- 62 HU, 6) common iliac artery: 260 +/- 114 HU, 7) superior vena
cava: 422 +/- 187 HU, and 8) inferior vena cava: 301 +/- 142 HU, showing
significantly higher values than the threshold value of 140 HU. Resuscitation
CEPMCT detected one case of pulmonary arterial thromboemboli death. CONCLUSION:
Resuscitation CEPMCT using chest compression immediately after death has the
possibility of detecting thromboembolus in major vessels, despite the simplicity
of the technique.
PMID- 24353979
TI - EEG-based analysis of human driving performance in turning left and right using
Hopfield neural network.
AB - In this article a quantitative analysis was devised assessing driver's cognition
responses by exploring the neurobiological information underlying
electroencephalographic (EEG) brain signals in a left and right turning
experiment on simulator environment. Driving brain signals have been collected by
a 19-channel electroencephalogram recording system. The driving pathway has been
selected with no obstacles, a set of indicators are used to inform the subjects
when they had to turn left or right by means of keyboard left and right arrows.
Subsequently in order to remove artifacts, preprocessing is performed on data to
achieve high accuracy. Features of signals are extracted by using Fast Fourier
Transform (FFT). Absolute power of FFT is used as a basic feature. Scalar Feature
selection method is applied to reduce feature dimension. Thereafter dimension
reduced features are fed to Hopfield Neural Network (HNN) recognizing different
brain potentials stimulated by turning to left and right. The performances of HNN
are evaluated by considering five conditions; before feature extraction, after
feature extraction, before reduction of features, after analyzing reduced
features and finally subject-wise Hopfield performances respectively. An increase
occurred in each level and continued until it has reached its highest 97.6% of
accuracy on last condition.
PMID- 24353981
TI - Is Health Related Quality of Life (HRQoL) a valid indicator for health systems
evaluation?
AB - The purpose of this review is to do a discussion about the use of the HRQoL as a
health measure of the populations that enable to analyze its potential use as a
measure of development and efficiency of health systems. The principal use of the
HRQoL is in health technologies economics evaluation; however this measure can be
use in public health when need to know the health state of population. The WHO
recognizes its potential use but its necessary to do a discussion about your
difficulties for its application and restrictions for its use as a performance
indicator for the health systems. The review show the different aspects about the
use of HRQoL how a measure of efficiency ot the health system, each aspect
identified in the literature is analyzed and discussed, developing the pros and
cons of their possible use, especially when it comes as a cardinal measure. The
analysis allows recognize that measuring HRQoL in countries could serve as a
useful indicator, especially when it seeks to measure the level of health and
disease, as do most of the indicators of current use. However, the methodological
constraints that do not allow comparability between countries especially when you
have large socioeconomic differences have yet to be resolved to allow comparison
between different regions.
PMID- 24353982
TI - Transarterial embolization (TAE) of sacral giant cell Tumor (GCT) using spherical
parmanent embolic material superabsorbant polymer microsphere (SAP-MS).
AB - PURPOSE: We retrospectively evaluated our experience of transcatheter arterial
embolization (TAE) of the sacral GCT with use of a spherical permanent embolic
agent, superabsorbant polymer microsphere (SAP-MS) as an alternative treatment
modality. MATERIALS AND METHODS: From 1997 to 2011, four patients with sacral GCT
were treated with TAE. In all cases, SAP-MS was used as an embolic material. The
effects of TAE were evaluated for improvement of patients' symptoms, radiographic
change such as vascularity of tumor, size of tumor and occurrence of
reossification. RESULTS: Of the four patients, three responded favorably to TAE
with improvement in pain and neurologic symptoms with long-term follow up.
Diminished vascularity, stabilization of tumor size and reossification were shown
radiographically. One patient died because of tumor growth 26 months after the
initial TAE. CONCLUSION: In sacral GCT, TAE using SAP-MS might be useful for
symptom improvement, reossification of the lesion and stabilization of tumor
size.
PMID- 24353983
TI - A cause of unbearably painful breast, diffuse dermal angiomatosis.
AB - Diffuse dermal angiomatosis is a rare disorder, considered to be a variant of
reactive cutaneous angioendotheliomatosis. The patients commonly present with
severe intractable breast pain and characteristic reticular violaceous
erythematous plaques with central ulcerations. Histologically, there is
infiltration of the recticular dermis by endothelial cells due to excess vascular
proliferation. Herein, we report a patient who presented with unbearable
bilateral breast pain with characteristic "reticular vascular marking" of her
breasts, who was diagnosed with diffuse dermal angiomatosis. We were able to
successfully treat our patient with a tapered isoretinoin regimen.
PMID- 24353984
TI - Ethical and Legal Issues in Biobanking for Genomic Research in Nigeria.
AB - The pursuit of genomic research and biobanking has raised concerns and
discussions about the ethical and legal implications. Given the specific
challenges that surround such enterprise in low and middle income countries, it
is pertinent to examine them in the light of the advent of Biobanking and Genomic
research in Nigeria. In this paper I discuss the issues and suggest model
solutions derived from advanced jurisdictions. These ethical and legal issues are
discussed within the context of the legal system of a typical African country
whose jurisprudence derives from that of its erstwhile colonial master, the
United Kingdom. This includes issues relating to law and human rights, informed
consent, native and customary law.
PMID- 24353986
TI - [The role of the pathologist in the diagnosis and therapy planning of central
nervous system tumors. Prognostic and predictive markers].
AB - Despite advances in imaging methods, the standard of diagnosis and treatment of
the tumours of the nervous system remains the histological report issued by a
neuropathologist. For reliable, definitive diagnosis, close collaboration with
other medical professions is essential, correlation of histological findings with
clinical and imaging results is necessary. Neuropathology became a subspecialty
because of the specific knowledge and experience it requires. In more complex
cases consultation with neuropathologists is important to ensure adequate
diagnosis and subsequent treatment. In both establishing the diagnosis and
treatment planning, the molecular testing of brain tumors becomes more and more
important. These tests are reliably available only in larger centers. Out of the
molecular markers, in current practice the investigation of codeletion at 1p/19q,
IDH mutations, beta-katenin nuclear positivity and MGMT methylation gained
acceptance. Besides these tests already in practice, a vast array of potential
diagnostic and prognostic markers are being investigated, which in the future may
assist in delivering better and more individualized therapy.
PMID- 24353985
TI - Autism as the Early Closure of a Neuroplastic Critical Period Normally Seen in
Adolescence.
AB - The most severe cases of autism are diagnosed by extreme social dysfunction and
other behavioral abnormalities. A number of genetic studies have been conducted
to correlate behavioral phenotypes to genetic dysfunctions, but no "autism gene"
has yet been discovered. In addition, environmental factors have been found to
influence the development of autistic traits with high probability. This review
will examine the role of a shortened period of neuroplasticity as a unifying
feature of the autistic phenotype. The neuroplastic period of interest normally
extends into adolescence, allowing for neural integration and the development of
language and social skills. Early closure of this period may result in a
shortened period of development, forcing the brain to rely on underdeveloped
structures.
PMID- 24353987
TI - [The role of extracellular matrix components in the invasion of intracranial
malignancies].
AB - The usual local recurrence of primary brain tumors is mainly due to the
infiltration of adjacent brain parenchyma by the glioma cells. This invasive
feature of the tumors makes total surgical excision impossible and also decreases
the efficacy of focal radiotherapy. Interestingly, intracerebral metastases
originating from many anaplastic tumors of other organs perform very moderate
peritumoral infiltration, therefore radical resection can be routinely achieved
and focal irradiation, even stereotactic radiotherapy, provides good tumor
control. Differences in the effectiveness of treatment between the two tumor
types derive from the remarkably different extent of peritumoral infiltration.
Thus significant molecular biological research has been dealing with the
infiltrative activity of various brain tumors and many attempts were made to
develop anti-invasive drugs for oncotherapy. This review summarizes the results
of these studies, describing cellular and molecular events of brain tumor
invasion and according potential oncotherapeutic possibilities.
PMID- 24353988
TI - [Results of postoperative radiochemotherapy of glioblastoma multiforme].
AB - Glioblastoma multiforme has one of the worst prognoses of all cancers. A
substantial progression in its treatment has been achieved only eight years ago
when a new adjuvant radiochemotherapy regimen containing temozolomid has been
introduced to the clinical practice. In this paper we evaluate the treatment
results in adjuvant radiochemotherapy of glioblastoma carried out by two
neurosurgery and oncology centers in Budapest, Hungary and we compared our
results to the data of the reference phase III registration trial of the
EORTC/NCIC. We analyzed the data of 210 patients treated for glioblastoma between
2005 and 2013. The primary endpoints of our study were overall survival and side
effects. We studied and statistically analyzed the influence of multiple factors
on survival. We compared our results with the data of the reference study and
other results published in the literature. The median follow-up for the surviving
patients in our study was 52 months. The median age of our patients was 58 (18
79) years. Seventy-two women and 138 men have been treated. The median overall
survival was 17 (3-96) months, the progression-free survival 11 (3-96) months.
The radiochemotherapy phase was completed in 95.2% and the monotherapy phase in
68% of all cases.Univariate analysis showed that age, ECOG status and RPA class
had significant influence on survival. In multivariate analysis only RPA class
remained statistically significant (RR 1.86, 95% CI 1.14-3.05). The proportion of
grade III and worse side effects during the chemoradiation phase was 3.8% and in
the monotherapy phase 1.9%. These were hematological side effects only. Serious
hematological sequelae occurred nearly exclusively in women. Comparing to the
reference study the demographic distribution of the patients was similar in our
study but among our patients there were less patients with unfavorable prognosis
(ECOG 2 or RPA V), and it resulted in a longer median survival than in the
original trial (17 vs. 14.6 months). With this analysis of our patients treated
according to the Stupp-protocol for glioblastoma multiforme we validated the
results of the original EORTC/NCIC study in a Hungarian patient population.
Moreover, this comparison proves that the comprehensive Hungarian neuro-oncology
service is not at all inferior when compared to any of the developed countries in
Europe.
PMID- 24353989
TI - [Treatment-induced tumor-like lesions in the course of neurooncological therapy].
AB - The proper interpretation of imaging changes in the course of multimodal
neurooncological therapy (neurosurgery, radiotherapy, chemotherapy, stereotactic
radiosurgery) is crucial. The appearance of abnormal or new contrast-enhancing
lesions does not indicate obvious tumor progression, in the contrary they are
frequently induced by the oncological therapy itself. The differentiation of real
tumor progression from therapy-induced lesions is essential, since the diagnosis
of progressive disease results in the termination of the current regimen and
initiation of second or third line therapy, if possible. The most common frequent
therapy-induced tumor-like lesions include the followings: pseudoprogression seen
at 1-3 months after the completion of concomittant radiochemotherapy of high
grade gliomas, real radiation necrosis which can develop even years after the
completion of fractionated external beam radiotherapy of gliomas, and radiation
necrosis seen after stereotactic radiosurgery delivered to metastatic brain
tumors. The absorbable hemostatic materials applied to the wall of resection
cavity during brain tumor surgery might cause delayed disturbancies in the blood
brain barrier, inducing abnormal signal changes and contrast enhancement
mimicking residual or recurrent tumor. Cerebrovascular ischemic lesions might
cause cortical enhancement in the subacute stage, which may be misinterpreted as
leptomeningeal tumor spread. The correct assessment of imaging findings requires
special knowledge and multidisciplinary consultation, therefore the treatment and
follow-up of brain tumor patients should be linked to brain tumor centers staffed
by experts in the field of neurosurgery, neurooncology and brain tumor imaging.
PMID- 24353990
TI - [Fractionated stereotactic irradiation of skull-base related tumours].
AB - The prognosis of the treatment of brain tumours depends on two main factors:
biological nature and localisation of the neoplasm. Requirements of oncologic
surgery can be met only partially if at all in neurological surgery of brain
tumours. Resectability depends primarily on localisation of the neoplasms. The
leading principle is preservation of fine neural structures, minimising morbidity
from tissue resection with the goal of maximal tumour resection. As nervous
structures and the target volume do not move in the intracranial space, large
radiation doses unusual in traditional radiotherapy can be given either in one or
in fractionated sessions to small targets (point-radiation) and a well-controlled
radiation necrosis of the pathological tissue can be achieved. Management
principles of treatment of skull-base related tumours are very similar due to
high risks of functional morbidity evoked by surgical injury to the cranial
nerves, brainstem structures, vessels of the Willis circle and those of the
substantia perforata anterior and posterior, etc. Such tumours are neoplasms
arising from the skull base, those infiltrating the cavernous sinuses, invasive
pituitary tumours, those arising from the glomus jugulare, or located within the
cerebello-pontine angle, etc. This manuscript intends to illustrate and prove the
hypothesis by means of 4 cases that fractionated stereotactic radiotherapy (fSRT)
is an important part of treatment armamentarium in the latter cases, as it is
capable of exploiting both the advantages of traditional fractionated irradiation
and that of the high conformality and selectivity of radiosurgery. It is capable
of administering appropriate quantity of total target dose with a lower than
limit dose on surrounding structures. The presentation proves that fSRT can be
planned already in the phase of surgical indication as a "microsurgery-assisted
radiotherapy".
PMID- 24353991
TI - [Antiangiogenic treatment of pediatric CNS tumors in Hungary with the Kieran
schedule].
AB - In Hungary a new oral antiangiogenic treatment was introduced in cases of primary
chemoresistant or recurrent pediatric CNS tumors, called Kieran schedule. The
early results of this treatment were analyzed. From 2010 at Semmelweis University
on individual decisions a daily combined per oral treatment was introduced in
pediatric patients with recurrent or progressive CNS tumor (Kieran schedule:
thalidomid, celecoxib, etoposid and cyclophosphamid). Efficacy of therapy was
analyzed in terms of demographic data, histology, side effects and tolerability
in a retrospective manner. From 2010 through 2013, twenty patients were treated
with Kieran schedule (medulloblastoma: 3, ependymoma: 5, anaplastic astrocytoma:
2, GBM: 4, plexus choroideus carcinoma: 1, central primitive neuroectodermal
tumor: 1, optic glioma: 2, brainstem tumor: 2). Median treatment time and median
progression-free survival were 0.60 and 0.61 years, respectively. Based on the
preliminary analysis of a limited cohort of patients, the therapy was efficient
in those cases of medulloblastoma, ependymoma, high-grade and optic gliomas,
where the expected survival time was more than 3 months at start of treatment.
Side effects were slight myelosuppresion in terms of previous therapy, 16%
transient ischemic attack (TIA)-like episodes. During therapy patients could live
their everyday life. Kieran schedule was well-tolerable and efficient with good
quality of life in certain cases of pediatric CNS tumors.
PMID- 24353992
TI - [Our experience with targeted therapy in glioblastoma multiforme].
AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain
tumor in adults. The current standard therapy includes surgical resection or
biopsy, followed by a combination of radiation and chemotherapy with
temozolomide. After progression or recurrence there is only one recommended
effective therapy, bevacizumab. Bevacizumab is a monoclonal VEGF inhibitor
antibody, inhibiting the angiogenesis in highly vascularized tumors. Resent
studies focused on adjuvant treatment with targeted therapy in newly diagnosed
tumors. Our purpose is to evaluate the data from patients treated in our
department investigate the clinical response and side effects profile and to
compare these data with the international results. The applied protocol was well
tolerated and side effects corresponded to the already reported ones. The median
PFS and survival data correlate with those in the literature. The AVAglio study
demonstrated that the addition of bevacizumab to the adjuvant therapy increased
PFS significantly.
PMID- 24353993
TI - [Fractionated conformal stereotactic irradiation of recurrent sacral tumour. Case
report and first description of the method in Hungary].
AB - Non-invasive procedures completing traditional surgical treatment play an
increasing role in the management of central nervous system malignancies.
Conformal stereotactic irradiation (radiosurgery) has become a routine method in
intracranial malignancies. However, application of this modality in tumours of
the spinal cord and spinal column is much more difficult to perform. It is
because extracranial organs can be only inaccurately fixed, and radio-sensitivity
of the spinal cord and risks of radionecrosis with ensuing paraplegia are high. A
recurrent sacrum chordoma treated by means of this modality - first reported in
Hungary - has been chosen for case presentation as the criteria for radiotherapy
such as high dose to target volume, minimal dose to neighbouring structures
highly sensitive to radiation are best met in these tumours by means of conformal
stereotactic radiotherapy. On the basis of further 13 extracranial cases treated
with this method one can conclude that high precision stereotactic conformal
radiotherapy offers up-grade to traditional radiotherapy despite the fact that it
is a time-consuming procedure. The oncological efficiency, the reduced risks of
side effects and the improved quality of life due to this treatment modality
compensate duly for the increased labour input.
PMID- 24353994
TI - [Preoperative embolisation of spinal metastases].
AB - In the management of spinal metastases bringing about neurological symptoms and
signs, palliative surgical treatment plays an important role. The goals of
surgery are preservation of neurological function especially that of the
mobility, pain relief and local tumor control. Many of spinal metastases are
hypervascularised, accordingly, preoperative embolisation offers logically
improvement in technical realisation of surgery by means of reduction of
intraoperative profuse bleeding. To prove this working hypothesis a retrospective
analysis was performed. Results of preoperative transarterial embolisation of
hypervascularised spinal tumours were worked up from 2000 to 2012. By means of 2
case presentations - to our knowledge, first in the Hungarian literature - the
techniques of transarterial spinal embolisation of spinal metastases are
described. Indications, complications and effect on intraoperative bleeding
events of the embolisation procedure in these oncological cases are presented on
the basis of literature search and of our own experience. The case analyses,
based mainly on qualitative retrospective data, support the notion that
histologically known spinal hypervascularised metastases or those found to be
hypervascularised by MRI can be treated effectively by means of preoperative
superselective embolisation without major risks of morbidity or mortality.
PMID- 24353995
TI - [Why is PET/CT essential in urooncology?].
AB - The wide use of molecular positron emission tomography/computed tomography
(PET/CT) imaging in the tumor diagnostics has been playing an important role
recently. The clinical role of hybrid imaging (PET/CT, single photon ECT/CT
(SPECT/CT)) is growing continuously due to the simultaneous imaging of anatomy
and function. Regarding oncology the role of (18)F-fluorodeoxyglucose ((18)F-FDG)
PET is proved in several clinical questions, including urooncology. Urologic
cancers are associated with low or slightly significant uptake of FDG, due to
their more benign behaviour. However, alternative PET tracers have been developed
which show promising clinical results and hopefully, in the near future the
combination of different tracers are awaited. Additionally, in the future the use
of multiparametric measurements, multitracer techniques, and the multimodal
PET/magnetic resonance imaging (PET/MRI) technology is going to have a crucial
clinical role.
PMID- 24353996
TI - Triptans for acute cluster headache.
AB - BACKGROUND: This is an updated version of the original Cochrane review published
in Issue 4, 2010 (Law 2010). Cluster headache is an uncommon,severely painful,
and disabling condition, with rapid onset. Validated treatment options are
limited; first-line therapy includes inhaled oxygen. Other therapies such as
intranasal lignocaine and ergotamine are not as commonly used and are less well
studied. Triptans are successfully used to treat migraine attacks and they may
also be useful for cluster headache. OBJECTIVES: To assess the efficacy and
tolerability of the triptan class of drugs compared to placebo and other active
interventions in the acute treatment of episodic and chronic cluster headache in
adult patients. SEARCH METHODS: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL),MEDLINE, EMBASE, ClinicalTrials.gov, and reference
lists for studies from inception to 22 January 2010 for the original review, and
from 2009 to 4 April 2013 for this update. SELECTION CRITERIA: Randomised, double
blind, placebo-controlled studies of triptans for acute treatment of cluster
headache episodes. DATA COLLECTION AND ANALYSIS: Two review authors independently
assessed study quality and extracted data. Numbers of participants with different
levels of pain relief,requiring rescue medication, and experiencing adverse
events and headache-associated symptoms in treatment and control groups were used
to calculate relative risk and numbers needed to treat for benefit (NNT) and harm
(NNH). MAIN RESULTS: New searches in 2013 did not identify any relevant new
studies.All six included studies used a single dose of triptan to treat an attack
of moderate to severe pain intensity. Subcutaneous sumatriptan was given to 131
participants at a 6 mg dose, and 88 at a 12 mg dose. Oral or intranasal
zolmitriptan was given to 231 participants ata 5 mg dose, and 223 at a 10 mg
dose. Placebo was given to 326 participants.Triptans were more effective than
placebo for headache relief and pain-free responses. By 15 minutes after
treatment with subcutaneous sumatriptan 6 mg, 48% of participants were pain-free
and 75% had no pain or mild pain (17% and 32% respectively with placebo).NNTs for
subcutaneous sumatriptan 6 mg were 3.3 (95% CI 2.4 to 5.0) and 2.4 (1.9 to 3.2)
respectively. Intranasal zolmitriptan 10mg was of less benefit, with 12% of
participants pain-free and 28% with no or mild pain (3% and 7% respectively with
placebo).NNTs for intranasal zolmitriptan 10 mg were 11 (6.4 to 49) and 4.9 (3.3
to 9.2) respectively. AUTHORS' CONCLUSIONS: Based on limited data, subcutaneous
sumatriptan 6 mg was superior to intranasal zolmitriptan 5 mg or 10 mg for rapid
(15 minute)responses, which are important in this condition. Oral routes of
administration are not appropriate.
PMID- 24353997
TI - Fluoxetine versus other types of pharmacotherapy for depression.
AB - BACKGROUND: Depression is common in primary care and is associated with marked
personal, social and economic morbidity, thus creating significant demands on
service providers. The antidepressant fluoxetine has been studied in many
randomised controlled trials (RCTs) in comparison with other conventional and
unconventional antidepressants. However, these studies have produced conflicting
findings.Other systematic reviews have considered selective serotonin reuptake
inhibitor (SSRIs) as a group which limits the applicability of the indings for
fluoxetine alone. Therefore, this review intends to provide specific and
clinically useful information regarding the effects of fluoxetine for depression
compared with tricyclics (TCAs), SSRIs, serotonin-noradrenaline reuptake
inhibitors (SNRIs), monoamineoxidase inhibitors (MAOIs) and newer agents, and
other conventional and unconventional agents. OBJECTIVES: To assess the effects
of fluoxetine in comparison with all other antidepressive agents for depression
in adult individuals with unipolar major depressive disorder. SEARCH METHODS: We
searched the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group
Controlled Trials Register (CCDANCTR)to 11May 2012. This register includes
relevant RCTs from the Cochrane Central Register of Controlled Trials (CENTRAL)
(all years),MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to
date). No language restriction was applied. Reference lists of relevant papers
and previous systematic reviews were handsearched. The pharmaceutical company
marketing fluoxetine and experts in this field were contacted for supplemental
data. SELECTION CRITERIA: All RCTs comparing fluoxetine with any other AD
(including non-conventional agents such as hypericum) for patients with unipolar
major depressive disorder (regardless of the diagnostic criteria used) were
included. For trials that had a cross-over design only results from the first
randomisation period were considered. DATA COLLECTION AND ANALYSIS: Data were
independently extracted by two review authors using a standard form. Responders
to treatment were calculated on an intention-to-treat basis: dropouts were always
included in this analysis. When data on dropouts were carried forward and
included in the efficacy evaluation, they were analysed according to the primary
studies; when dropouts were excluded from any assessment in the primary studies,
they were considered as treatment failures. Scores from continuous outcomes were
analysed by including patients with a final assessment or with the last
observation carried forward. Tolerability data were analysed by calculating the
proportion of patients who failed to complete the study due to any causes and due
to side effects or inefficacy. For dichotomous data, odds ratios (ORs) were
calculated with 95% confidence intervals (CI) using the random-effects model.
Continuous data were analysed using standardised mean differences (SMD) with 95%
CI. MAIN RESULTS: A total of 171 studies were included in the analysis (24,868
participants). The included studies were undertaken between 1984 and 2012.
Studies had homogenous characteristics in terms of design, intervention and
outcome measures. The assessment of quality with the risk of bias tool revealed
that the great majority of them failed to report methodological details, like the
method of random sequence generation, the allocation concealment and blinding.
Moreover, most of the included studies were sponsored by drug companies, so the
potential for overestimation of treatment effect due to sponsorship bias should
be considered in interpreting the results. Fluoxetine was as effective as the
TCAs when considered as a group both on a dichotomous outcome (reduction of at
least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24
RCTs, 2124 participants) and a continuous outcome (mean scores at the end of the
trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50
RCTs, 3393 participants). On a dichotomousoutcome, fluoxetine was less effective
than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat
(NNT) =6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI
1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine
(OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600
participants) and venlafaxine(OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to
16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more
effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141
participants) and milnacipran (SMD -0.36, 95% CI-0.63 to -0.08, 2 RCTs, 213
participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95%
CI 0 to 0.19, 13 RCTs,3097 participants). Fluoxetine was better tolerated than
TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96;NNT = 20,
95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in
comparison with individual ADs, in particular amitriptyline (total dropout OR
0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants),
and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT
= 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole(total dropout OR 0.12,
95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and
reboxetine (total dropout OR0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4
RCTs, 764 participants). AUTHORS' CONCLUSIONS: The present study detected
differences in terms of efficacy and tolerability between fluoxetine and certain
ADs, but the clinical meaning of these differences is uncertain.Moreover, the
assessment of quality with the risk of bias tool showed that the great majority
of included studies failed to report details on methodological procedures. Of
consequence, no definitive implications can be drawn from the studies' results.
The better efficacy profile of sertraline and venlafaxine (and possibly other
ADs) over fluoxetine may be clinically meaningful,as already suggested by other
systematic reviews. In addition to efficacy data, treatment decisions should also
be based on considerations of drug toxicity, patient acceptability and cost.
PMID- 24353998
TI - A new strategy to eliminate sample mixing during in-tube solid phase
microextraction.
AB - During in-tube solid phase microextraction, sample mixing with mobile phase
contained in the autosampler tubing during extraction may result in some amount
of sample becoming entrained in the mobile phase rather than returning to the
sample vial or being directed to waste after extraction. In cases where target
analytes have relatively low affinity for the sorbent on the wall of the
capillary, mixing can impact data quality. Where the sample contains components
that may interfere with either the separation (e.g. proteins) or detection (e.g.
ions with MS detection), additional difficulties can arise. In the current
research, the magnitude of the sample mixing effect was illustrated by analyzing
ranitidine and a series of polycyclic aromatic hydrocarbons (PAH). The sample
volume equivalent of mixing was calculated as 37 MUL for ranitidine and 20 MUL
for PAHs using the same inner diameter of capillary. To address this issue, a
novel approach involving adding a switching valve located between the metering
pump and the capillary was developed. Capillary flush conditions, draw/eject
speed and extraction time were optimized for ranitidine with the result that in
the final method, no mixing of sample with mobile phase was apparent in the
detected amounts. To provide information on a compound class with intermediate
polarity, two -blockers were also extracted using the optimized washing
conditions respectively. The results indicated that the issue of sample mixing
had been resolved for these as well. Finally, in-tube SPME calibration of these
three analyte classes was shown to be highly linear, providing further indication
that sample mixing was not impacting data quality. Available literature on the
subject was surveyed, and a discussion on the rational selection of conditions to
guide method development was also provided.
PMID- 24353999
TI - In situ derivatization coupled to microextraction by packed sorbentand gas
chromatography for the automated determination ofhaloacetic acids in chlorinated
water.
AB - A novel analytical method is reported for the determination of monochloroacetic
acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and
dibromoacetic acid. These are the five haloacetic acids (HAAs) for which the U.S.
Environmental Protection Agency (US EPA) has regulated a maximum contamination
level (MCL) of 0.060 mg L-1for the sum of their concentrations in drinking
waters. Themethod uses in situ aqueous derivatization, followed by
microextraction by packed sorbent (MEPS) priorto gas chromatography-mass
spectrometry (GC-MS). The parameters affecting derivatization and extraction were
optimized with a view to obtaining maximum sensitivity. The HAAs were derivatized
with 2,2,2-trifluroethylamine (TFEA), using N-ethyl-N'-(3-dimethylaminopropyl)
carbodiimide (EDC) as a condensation agent. The reaction occurred in aqueous
medium and was carried out in 10 min in the vial of anautosampler used to perform
microextraction by packed sorbent. The whole process, from the mixing of the
reagents for the derivatization, was automated. Precision values varied from 4.2
to 9.8% (as intra-day relative standard deviation, RSD) and 9.4 to 14% (as inter
day RSD). The recoveries from spiked concentrations ranged from 83 to 117%,
revealing the accuracy of the method. The detection limits ranged from 0.36 to
1.2 g L-1, such that it is possible to measure the US EPA MCL in drinking waters.
The method developed was applied to the analysis of HAAs in drinking and swimming
pool water from Salamanca(North West of Spain).
PMID- 24354000
TI - In-tube solid-phase microextraction with molecularly imprinted polymer to
determine interferon alpha 2a in plasma sample by high performance liquid
chromatography.
AB - A molecularly imprinted sol-gel polymer (MIP) based on protein
(biopharmaceutical) template with a mild template removal condition using
protease was synthetized and evaluated as stationary phase for in-tube solid
phase microextraction (in-tube SPME) of the interferon alpha 2a from plasma
samples,followed by high performance liquid chromatography analysis with
fluorescence detection (HPLC-FD).The developed MIP exhibited high selectivity for
the analyte in a complex matrix. The in-tube SPME variables such as draw/eject
cycles, draw/eject volume, and desorption conditions were optimized to establish
the equilibrium conditions in a short time. The MIP in-tube SPME/HPLC-FD method
presented linear response over a dynamic range of 8-300 ng mL-1, with a
correlation coefficient of 0.997. The inter-assay precision presented coefficient
of variation lower than 9.2%, and accuracy values between 92% and 98%. The
developed MIP performed as well as other selective interferon alpha 2a stationary
phases (e.g.,immunosorbent and restricted access material), with the advantage
that it is robust, easy to handle and cheap to synthesize, in a addition to
requiring smaller sample volume (50 L). Based on the analytical validation
results, the proposed method (MIP in-tube SPME/HPLC-FD) can be a useful tool to
determine interferon alpha 2a in plasma samples from patients receiving
therapeutic dosages.
PMID- 24354001
TI - Stir bar sorptive extraction combined with high performance liquid chromatography
ultraviolet/inductively coupled plasma mass spectrometry for analysis of
thyroxine in urine samples.
AB - tIn this work, polyethyleneglycol (PEG)/hydroxyl polydimethylsiloxane (OH
PDMS)/gamma -mercaptopropyltrimethoxysilane (gamma -MPTS) coated stir bar was
prepared by sol-gel process and its extraction performance for the extraction of
amphoteric thyroxines (3,3',5,5'-tetraiodothyronin, T(4); 3,3',5
triiodothyronine, T(3); reversed-3,3',5-triiodothyronine, rT(3)) and their
metabolite (3,5-diiodothyronine,T2) was studied. The preparation reproducibility
of PEG/OH-PDMS/gamma -MPTS coated stir bar was investigated, and the relative
standard deviations (RSDs) in the same batch and among different batches were 3.3
14.3% (n = 5) and 7.7-16.6% (n = 3), respectively. The prepared PEG/OH-PDMS/gamma
-MPTS coated stir bar could be reused for more than 20 times. Based on this fact,
a novel method of stir bar sorptive extraction (SBSE) combined with high
performance liquid chromatography (HPLC)-ultraviolet (UV)and HPLC-inductively
coupled plasma mass spectrometry (ICP-MS) for the analysis of target thyroxinesin
human urine samples was developed. The influencing factors of SBSE, such as
sample pH, extraction time, stirring rate, salt effect, desorption solution and
desorption time, were studied in detail, and the analytical performance of the
proposed method was evaluated under the optimized conditions. The enrichment
factors (EFs) of the developed method for four target thyroxines were in the
range of 14.9-70.4(theoretical enrichment factor was 100). The RSDs were ranging
from 4.0% to 13.8% for SBSE-HPLC-UV (c = 25 MUg/L, n = 6) and from 3.7% to 6.1%
for SBSE-HPLC-ICP-MS (c = 0.5 MUg/L, n = 5). The linear range obtained by SBSE
HPLC-UV was 2-500 MUg/L for T(2)and 5-500 MUg/L for rT3, T(3)and T(4), with
correlation coefficients (r) ranging from 0.9957 to 0.9998, respectively, while
the linear range obtained by SBSE-HPLC-ICP-MS was 0.05-500 MUg/L for T(2) and
rT(3), 0.10-200 MUg/L for T(3) and 0.05-200 MUg/L for T(4)with r ranging from
0.9979 to 0.9998, respectively. The limits of detection (LODs) for the target
thyroxines were 0.60-2.20 MUg/L for SBSE-HPLC-UV and 0.0071-0.0355 MUg/L SBSE
HPLC-ICP-MS, respectively. The developed method was applied for the determination
of target thyroxines in urine samples, and the recovery for the spiking samples
obtained by SBSE-HPLC-UV was in the range of 81.6-137.6% for human urine,while
the recovery for the spiking urine samples obtained by SBSE-HPLC-ICP-MS were in
the range of 72.0-121.5%.
PMID- 24354002
TI - Semiautomated solid-phase extraction followed by derivatisation and gas
chromatography-mass spectrometry for determination of perfluoroalkyl acids in
water.
AB - This paper describes a sensitive approach for the determination of 6
perfluoroalkyl carboxylic acids and perfluorooctane sulfonic acid in water.
Samples were preconcentrated using an automatic solid-phase extraction module and
then manually derivatised and determined by gas chromatography-mass spectrometry.
The analytes were derivatised with a isobutyl chloroformate/isobutanol mixture,
using 3% N,N-dicyclohexylcarbodiimide in pyridine as the catalyst. From a
systematic comparison of several reversed-phase and anion-exchange sorbent
materials for the retention of perfluoroalkyl acids, the high-est retention
efficiencies (~100%) were achieved with LiChrolut EN and Discovery DSC-SAX
columns.LiChrolut EN was the sorbent selected due to several advantages (sample
pH ~1; sample flow rate,5.5 mL/min; breakthrough volume, 300 mL) over Discovery
DSC-SAX (sample pH ~6; sample flow rate,3.0 mL/min; breakthrough volume, 45 mL),
for the retention of the studied compounds. Detection and quantification limits
within the range of 0.1-0.5 ng/L and 0.4-1.7 ng/L, respectively, were obtained
for a sorbent column of 70 mg of LiChrolut EN and 250 mL of sample, the relative
standard deviation being lower than 7%. The method was applied both to the
analysis of water collected at the intake (raw) and atthe exit (treated) of two
drinking water treatment plants, as well as to various types of water. Few
samples were positive for perfluoroalkyl acids and only one acid
(perfluoroheptanoic or perfluorooctanoic) was found in each treatment plant. The
highest number and concentration of analytes
(perfluoroheptanoic,perfluorooctanoic and perfluorodecanoic acid) were found in
one wastewater.
PMID- 24354003
TI - Methods development in multimodal chromatography with mobile phase modifiers
using the steric mass action model.
AB - The ability to predict downstream protein purification processes is of great
value in the biopharmaceutical industry; saving time, cost and resources. While
many complex models exist, the appropriate use of simple models can be a useful
tool for rapidly designing and optimizing processes as well as for risk analysis
and establishing parameter ranges. In this study, the steric mass action isotherm
is success-fully employed to predict the chromatographic behavior of a multimodal
anionic Capto adhere systemin the presence of various mobile phase modifiers. An
experimental protocol consisting of only a few column experiments is shown to be
sufficient to establish the model. Proof of concept is carried out using human
insulin and bovine serum albumin which have varying degrees of hydrophobicity,
charge and size. Finally, the model predictions are verified under various
experimental conditions and the unique selectivity of this multimodal system is
explored and compared with traditional anion exchange resins.The simple model
approach described here represents a rapid and useful method for model based
process development of multimodal chromatography.
PMID- 24354004
TI - Slurry concentration effects on the bed morphology and separation efficiency of
capillaries packed with sub-2 MUm particles.
AB - Transcolumn dispersion limitations on the separation efficiency of
chromatographic columns suggest the need for packing methods that increase bed
homogeneity and minimize potential wall effects. Here we address the influence of
the slurry concentration in the slurry packing process on the resulting
morphology and separation efficiency of ultrahigh-pressure liquid chromatography
capillary columns.30-75 MUm i.d. capillaries were packed with fully porous 0.9,
1.7, and 1.9 MUm bridged-ethyl hybrid particles and 1.9 MUm Kinetex core-shell
particles. Capillaries prepared with higher slurry concentrations(20-100 mg/mL)
showed higher separation efficiencies than those prepared using a low slurry con
centration (2-3 mg/mL). The effect is explained by an analysis of transcolumn bed
heterogeneities in three-dimensional reconstructions acquired from the packed
capillaries using confocal laser scanning microscopy. The three-dimensional
analysis of porosity distributions and local particle size illustrates that beds
packed with higher slurry concentrations suppress particle size segregation,
however, at the expense of a larger amount of packing voids. In core-shell
packings, where only few packing voids were found, the higher slurry
concentration allowed for an additional densification of the bed's wall region,
as revealed by a radial analysis of the mean particle distances. Overall, wall
effects are attenuated in packed columns prepared with both wide and narrow
particle size distributions, which will allow for improved chromatographic
performance.
PMID- 24354005
TI - Ultrathin-layer chromatography on SiO(2), Al(2)O(3), TiO(2), and ZrO(2)
nanostructured thin films.
AB - We explored four different inorganic oxides and determined their merits in
miniaturized planar chromatography. Despite progression of chromatographic
techniques over several decades, such alternatives to traditional planar silica
gel stationary phases have not been fully evaluated. Glancing angle
deposition(GLAD) provided an excellent platform for engineering nanostructured
thin films in these materials for ultrathin-layer chromatography (UTLC).
Separations of carotenoids and synthetic food dyes were used to investigate the
attributes of SiO(2), Al(2)O(3), TiO(2), and ZrO(2)GLAD UTLC media. These
anisotropic high surface area thin films possessed similar channel-like features
but different chromatographic properties.TiO(2)and ZrO(2)media were especially
interesting since analyte retention could be modified through sim-ple oxidation
heat treatments and UV irradiation. Generally, oxidation reduced analyte
retention while UV exposure increased retention. Changes in retention factor as
large as DeltahRF~ 40 (for Acid Red 14 on titanium oxide) were achieved. Food dye
mixtures were applied using consumer inkjet printers as per the Office
Chromatography concept and separation performance was quantified using advanced
video instrumentation designed for miniaturized plates. Enhanced time-resolved
UTLC methods were used to calculate figures of merit from recorded dye separation
videos. Small theoretical plate heights (<4 MUm)and low limits of detection (<2
ng per zone for the food dye tartrazine) were measured. The combination of
engineered GLAD UTLC plates, inkjet application of analyte spots, time-resolved
UTLC, and custom analysis algorithms enabled some of the best performance
achieved on GLAD UTLC layers. Separations on the inorganic oxide thin films were
also successfully hyphenated with electrospray ionization mass spectrometry for
the first time. This investigation demonstrates the utility of alternative
inorganic oxide GLADUTLC media and probes avenues of expanding the capabilities
of miniaturized planar chromatography.
PMID- 24354007
TI - Chromatographic adhesion law to simplify surface energy calculation.
AB - The calculated data of inverse gas chromatography (IGC) vary depending on the
calculation methods and the n-alkane series. To overcome IGC data variability,
this paper combines the Van Oss-Good-Chaudhury concept, the Dorris-Gray equation,
the Schultz equation, the Fowkes equation and group contribution theory to
establish the chromatographic adhesion law and its equation is K(a)(i)
=e(DeltaEai /kT) . In the equation, K(ai) is the adhesion retention factor of a
chemical group, DeltaE(ai) represents the increased chromatographic adhesion
energy due to this group and kT expresses the thermal kinetic energy of the
molecule contain-ing this group. The dispersive component (gamma(dS) ), the
electron acceptor component (gamma(+S) ) and the electron donor component (gamma(
S)) of a solid surface are then calculated from DeltaE(ai) . Through correlating
the retention time with the adhesion energy, this law expresses mathematically
the chromatographic adhesion phenomenon of IGC at the infinite dilution region.
This paper also derives a new equation to calculate the retention time of a non
adsorbing probe (dead retention time).
PMID- 24354006
TI - A microchip electrophoresis-mass spectrometric platform for fast separation and
identification of enantiomers employing the partial filling technique.
AB - A microchip electrophoresis-mass spectrometric (MCE-MS) method was developed for
fast chiral analysis. The proposed MCE-MS platform deployed a glass/PDMS hybrid
microchip with an easy-to-fabricate monolithic nanoelectrospray emitter.
Enantiomeric MCE separation was achieved by means of the partial filling
technique. A novel chip design with an arm channel connecting to the middle of
the MCE separation channel for delivering the chiral selector was tested and
proven valid. Enantiomeric separation of3.4-dihydroxyphenylalanine (DOPA),
glutamic acid (Glu), and serine (Ser), the selected test compounds,were achieved
within 130 s with resolution values (R(s)) of 2.4, 1.1, and 1.0, respectively.
The proposed chiral MCE-MS assay was sensitive and had detection limits of 43 nM
for l-DOPA and 47 nM for d-DOPA.The analytical platform was well suited for
studies of stereochemical preference in living cells because it integrated cell
culture, sample injection, chiral separation, and MS detection into a single
platform.Metabolism of DOPA in human SH-SY5Y neuronal cells was studied as a
model system. On-chip incubation of SH-SY5Y cells with racemic DOPA was carried
out, and the incubation solution was injected and in-line assayed at time
intervals. It was found that l-DOPA concentration decreased gradually as
incubation time increased while the concentration of coexisting d-DOPA remained
constant. The results firmly indicated that SH-SY5Y cells metabolized l-DOPA
effectively while left d-DOPA intact.
PMID- 24354008
TI - Fingerprinting polychlorinated biphenyls in environmental samples using
comprehensive two-dimensional gas chromatography with time-of-flight mass
spectrometry.
AB - A GC * GC-TOFMS installed with a Rtx-PCB (60 m * 0.18 mm * 0.18 MUm) in the first
dimension and Rxi- 17 (1.5 m * 0.1 mm * 0.1 MUm) column in the second dimension
was used to separate 188 out of 209 congeners. A further 12 congeners were
identified through additional data processing resulting in the identification of
a total of 200 congeners. However, caution is advised if these 12 congeners were
to be used in quantitative assessments. The remaining 9 co-eluting congeners were
three doublets (CB65 + CB62, CB160 + CB163 and CB201 + CB204) and one triplet
(CB20 + CB21 + CB33). This method was tested on five Aroclors and resulted in the
separation of all congeners present in the heavier Aroclor mixtures A1254 and
A1260. The suitability of this method for applications in biological matrices was
demonstrated on extracted whiting and guillemot liver samples which resulted in
the identification of 137 individual PCBs in the whiting liver sample and 120 in
the guillemot sample. Fingerprinting was able to show clear differences in the
PCB signature of the two animals. This highlights the potential of this method
for PCB fingerprinting in environmental forensics studies and other assessments
that require congener specific analysis.
PMID- 24354009
TI - Cutaneous thrombosis in PNH.
PMID- 24354010
TI - Chediak-Higashi-like granules within leukemic promyelocytes.
PMID- 24354011
TI - Baseline plasma N-terminal pro-B-type natriuretic peptide is associated with the
extent of stress-induced myocardial ischemia during dobutamine stress
echocardiography: Retraction.
AB - Feringa HH, Elhendy A, Bax JJ, Boersma E, de Jonge R, Schouten O, et al. Baseline
plasma N-terminal pro-B-type natriuretic peptide is associated with the extent of
stress-induced myocardial ischemia during dobutamine stress echocardiography.
Coron Artery Dis 2006; 17:255-259.---A Committee established by the Board of
Erasmus Medical Center, The Netherlands, that reported in September 2012,
considers the reporting of the research by Feringa et al. to have been negligent
and scientifically incorrect according to two criteria: the inclusion and
exclusion criteria reported in the publication were not applied consistently,
with the result that the patient population actually studied differs in material
ways from the published description; and, there are material differences between
the source documentation (the patients' dossier), the case record form used in
the study, the study database, and the publication. For this reason the article
by Feringa et al. is retracted from publication.
PMID- 24354012
TI - SUMOylation in neuroplasticity and neurological disorders.
PMID- 24354013
TI - Post-mastectomy reconstruction: a risk-stratified comparative analysis of
outcomes.
AB - INTRODUCTION: Although breast reconstruction following mastectomy plays a role in
the psychological impact of breast cancer, only one in three women undergo
reconstruction. Few multi-institutional studies have compared complication
profiles of reconstructive patients to non-reconstructive. METHODS: Using the
National Surgical Quality Improvement database, all patients undergoing
mastectomy from 2006 to 2010, with or without reconstruction, were identified and
risk-stratified using propensity scored quintiles. The incidence of complications
and comorbidities were compared. RESULTS: Of 37,723 mastectomies identified, 30%
received immediate breast reconstruction. After quintile matching for
comorbidities, complications rates between reconstructive and non-reconstructives
were similar. This trend was echoed across all quintiles, except in the sub-group
with highest comorbidities. Here, the reconstructive patients had significantly
more complications than the non-reconstructive (22.8% versus 7.0%, p < 0.001).
CONCLUSION: Immediate breast reconstruction is a well-tolerated surgical
procedure. However, in patients with high comorbidities, surgeons must carefully
counterbalance surgical risks with psychosocial benefits to maximize patient
outcomes. LEVEL OF EVIDENCE: Level 3.
PMID- 24354014
TI - Back from the brink.
AB - Against the backdrop of a global loss of biodiversity, some wildlife species have
recovered from severe decimation, as a recent report shows for dozens of species
in Europe. While these encouraging signs don't diminish the current crisis of
species loss, the analysis of the underlying reasons--ranging from targeted
conservation measures to unintended consequences of changes in human behaviour-
can help researchers understand what measures may help to save other species as
well. Michael Gross reports.
PMID- 24354015
TI - Keiko U. Torii.
PMID- 24354017
TI - The future of cardiology.
PMID- 24354016
TI - Cognitive tomography reveals complex, task-independent mental representations.
AB - Humans develop rich mental representations that guide their behavior in a variety
of everyday tasks. However, it is unknown whether these representations, often
formalized as priors in Bayesian inference, are specific for each task or
subserve multiple tasks. Current approaches cannot distinguish between these two
possibilities because they cannot extract comparable representations across
different tasks. Here, we develop a novel method, termed cognitive tomography,
that can extract complex, multidimensional priors across tasks. We apply this
method to human judgments in two qualitatively different tasks, "familiarity" and
"odd one out," involving an ecologically relevant set of stimuli, human faces. We
show that priors over faces are structurally complex and vary dramatically across
subjects, but are invariant across the tasks within each subject. The priors we
extract from each task allow us to predict with high precision the behavior of
subjects for novel stimuli both in the same task as well as in the other task.
Our results provide the first evidence for a single high-dimensional structured
representation of a naturalistic stimulus set that guides behavior in multiple
tasks. Moreover, the representations estimated by cognitive tomography can
provide independent, behavior-based regressors for elucidating the neural
correlates of complex naturalistic priors.
PMID- 24354018
TI - Reply: To PMID 23220510.
PMID- 24354042
TI - [IV. Is oxaliplatin effective as adjuvant chemotherapy for stage III rectum
cancer post operation?].
PMID- 24354043
TI - [Surgery for sinonasal inverted papilloma].
PMID- 24354044
TI - [Diagnosis and treatment for salivary gland disease].
PMID- 24354045
TI - [Treatment in children patients with dysphagia].
PMID- 24354046
TI - The ABFM begins to use differential item functioning.
PMID- 24354047
TI - What's behind health insurance rate increases? an examination of what insurers
reported to the federal government in 2012-2013.
AB - The Affordable Care Act requires health insurers to justify rate increases of 10
percent or more for nongrandfathered plans in the individual and small-group
markets. Analyzing these filings for rates taking effect from mid-2012 through
mid-2013, insurers attributed the great bulk--three-quarters or more--of these
larger rate increases to routine factors such as trends in medical costs.
Insurers attributed only a very small portion of these medical cost trends to
factors related to the Affordable Care Act. The ACA-related factor mentioned most
often, but only in a third of the rate filings in this study, was the requirement
to cover women's preventive and contraceptive services without patient cost
sharing. But, the insurers who point to this requirement or other ACA-related
costs attributed only about 1 percentage point of their rate increases to the
health reform law.
PMID- 24354048
TI - How are state insurance marketplaces shaping health plan design?
AB - Part of states' roles in administering the new health insurance marketplaces is
to certify the health plans available for purchase. This analysis focuses on how
state-based and state partnership marketplaces are using their flexibility in
setting certification standards to shape plan design in the individual market. It
focuses on three aspects of certification: provider networks; inclusion of
essential community providers; and benefit substitution, which allows plans to
offer benefits that differ from a state's benchmark plan. A review of documents
collected from 18 states and the District of Columbia finds that 13 states go
beyond the minimum federal requirements with respect to provider network
standards, four states specify additional standards for including essential
community providers, and five states and Washington, D.C., bar benefit
substitution. These interstate variations in plan design reflect the challenges
policymakers face in balancing health care affordability, benefit coverage, and
access to care through the marketplace plans.
PMID- 24354050
TI - [Application of genomics technology in Chinese medicine and pharmacy].
PMID- 24354049
TI - [Progress of treating Alzheimer's diseases by "A beta cascade hypothesis" based
Chinese materia medica].
PMID- 24354051
TI - Silent myocardial ischemia: a challenge in management.
PMID- 24354052
TI - Author's reply: To PMID 23641748.
PMID- 24354053
TI - On influence...
PMID- 24354054
TI - The chief concern of medicine.
PMID- 24354055
TI - In women over 35 years of age who smoke, does mirena (levonorgestrel-releasing
intrauterine system) reduce the risk of DVTs compared to oral contraceptives?
PMID- 24354056
TI - Are antibiotics beneficial in the treatment of patients with acute uncomplicated
diverticulitis?
PMID- 24354057
TI - The growing role of genetics in medical care.
PMID- 24354058
TI - [Vaccines against highly pathogenic influenza viruses of the avian origin].
AB - Worldwide spreading of H5 and H7 highly pathogenic influenza viruses of the avian
origin, which periodically infect and kill humans without prior adaptation, poses
a constant threat of the new pandemic. The effectiveness of the pandemic
prevention completely depends on the quality of the existing influenza vaccines.
Typical methods of the vaccine production from the antigenically relevant strains
are problematic in case of high virulent H5 and H7 viruses. Therefore, new
approaches to the construction of the vaccine strains and production technologies
are required in order to protect the population.
PMID- 24354059
TI - [The Khurdun virus (KHURV): a new representative of the orthobunyavirus
(Bunyaviridae)].
AB - Unidentified Khurdun virus (KHURV) was isolated in 2001 from coot (Fulica atra,
Linnaeus, 1758) in the Volga River delta (Astrakhan Region, Russian Federation).
Here we report that the KHUV genome was de novo sequenced (on Illumina platform)
and the KHURV was classified as a novel prototypic bunyavirus. The KHURV genome
comprises three negative-sense RNA segments (L, M, and S); its terminal
nucleotide sequences are canonical for the Orthobunyavirus genus. Based on the
results of the molecular-genetic and phylogenetic analysis we suggest that the
KHURV belongs to the genus Orthobunyavirus (Bunyaviridae).
PMID- 24354060
TI - [Molecular-genetic characterization of the Bhanja virus (BHAV) and the Razdan
virus (RAZV) (Bunyaviridae, Phlebovirus) isolated from the Ixodes ticks
Rhipicephalus bursa (Canestrini and Fanzago, 1878) and Dermacentor marginatus
(Sulzer, 1776) in transcaucasus].
AB - Two bunyaviruses, Bhanja (BHAV, LEIV-Az1818) isolated from the Ixodes ticks
Rhipecephalus bursa (Canestrini and Fanzago, 1878) in Azerbaijan (1973) and
Razdan (RAZV; strain LEIV-Arm2741) isolated from the Dermacentor marginatus
(Sulzer, 1776) ticks in Armenia (1972), were de novo sequenced (on the Illumina
platform). The amino acid identity between these viruses proteins were 95.8%
(RdRp, L-segment), 90.3% (GnGc, M-segment), and 92.5% (N, S-segment). Thus, RAZV
was classified to BHAV group. GnGc protein identity of RAZV withEuropean BHAV
strains is more than 90%. With the African Forecariah virus (FORV) RAZV has 85%
identity. BHAV LEIV-Az1818 is most closely related to the Indian strain BHAV
IG690 (99%), while showing 90% identity with the European BHAV isolates. The
genome structure of BHAV and RAZV is typical of the tick-transmitted
phleboviruses. Based onthe result of the molecular-genetic and phylogenetic
analysis RAZV has been classified as belonging to BHAVgroup in the genus
Phlebovirus (Bunyaviridae).
PMID- 24354061
TI - [Pathogenic effect of pandemic influenza virus H1N1 under replication in cultures
of human cells].
AB - The propagation of the pandemic influenza virus H1N1 in cultures of bronchial
(Calu-3) and intestinal (Caco-2) differentiated epithelial cells of human origin
was studied. The canine epithelial cell lines, MDCK-H and MDCK-2, were
comparatively tested. The two human cell lines were found to be highly sensitive
to the influenza pandemic strains A/Hamburg/05/09 and A/Moscow/501/2011 and
maintained their replication without addition of trypsin to culture medium. Virus
strains of seasonal influenza H1N1, such as A/Moscow/450/2003, A/Memphis/14/96,
and laboratory strain A/PR/8/34, multiplied in these human cells in similar
manner. The intracellular cleavage HA0-->HA1+HA2 by the host virus-activating
protease (IAP) occurred in both human cell lines under infection with each
influenza virus H1N1 including pandemic ones. Comparatively, this cleavage of all
influenza H1N1 virus strains appeared to be either undetectable or low-detectible
in MDCK-H and MDCK-2, respectively, thereby implying low levels of active IAP in
these cells. Multiplication of pandemic and seasonal influenza H1N1 viruses in
Calu-3 and Caco-2 cells caused cytopathic effect, which was accompanied with low
autophagy and apoptosis events. These data allow recommending human cell lines,
Calu-3 and Caco-2, for optimized isolation and passaging of clinical strains of
Influenza pandemic viruses H1N1.
PMID- 24354062
TI - [HIV-1 genetic variants in the Asian part of Russia: a study (2005-2010)].
AB - The HIV-1 genetic variants circulated in the Asian part of the Russian Federation
in 2005-2010 were studied. The samples of HIV-1 (427 in total) were collected in
Khabarovsk, Magadan, Kurgan, Krasnoyarsk, Noyabr'sk, Yakutsk, Altay, and Tyva.
Sequencing of some genome regions followed by the phylogenetic analysis or
specific Internet resource sampling were used as the main methods of the HIV
subtyping. The domination of the IDU-A HIV-1 genetic variant typical of HIV
infection epidemic in Russia was shown in all regions tested in 2005-2010. This
variant prevailed both in IDUs and heterosexuals. In addition to IDU-A, some
other HIV-1 genetic variants were found among them: subtype B and recombinant
CRF03_AB. The HIV-1 genetic polymorphism in Russia was found to be low. An
increase in the genetic distance among studied de novo samples was noted in the
Asian part of Russia in 2005-2010 (26-68%) as compared to the European variants
in 1996-1999 (10%).
PMID- 24354063
TI - [Immunomodulators and specific inactivated vaccines in urgent prophylaxis under
experimental arboviral infection].
AB - A reliable protective activity of the home-manufactured immunomodulators
(ridostin, polyribonate glucosemuramyl-dipeptide, Mylife, and peptidoglycane-160)
was detected in mice. The mice were infected with the equine eastern
encephalomyelitis virus (EEEV, an alphavirus), or with the tick-borne
encephalitis virus (TBEV), or the yellow fever (YF) virus (both flaviviruses).
The effect of the urgent vaccination reliably increases when the vaccination is
combined with the immunomodulators listed above. Under the alphavirus infection,
the combined effects of the vaccine and ridostin were accompanied with increased
specific humoral and cellular immune response (virus-specific antibodies and
adoptive transfer of immune lymphocytes). The combined application of the
specific vaccine and ridostin can be recommended for clinical trials of TBE in
the foci of Infection.
PMID- 24354064
TI - [A comparative study of the antiviral activity of chemical compounds concerning
the orthopoxviruses experiments in vivo].
AB - In the experiments using intranasal (i/n) infection of mice with the ectromelia
virus (EV) in a dose 10 LD50/head (10 x 50% lethal doselhead) or with the
monkaypox virus (MPXV) in a dose 10 ID50/head (10 x 50% infective dose/ head) it
was demonstrated that the antiviral efficiency of chemical compounds - the
condensed derivatives of pyrrolidin-2,5-dion, as well as their predecessors and
the nearest analogues, synthesized in Novosibirsk Institute of Organic Chemistry
of the Siberian Branch of the Russian Academy of Sciences (NIOCH SB RAS) was
observed. As a positive control we used the antipoxvirus chemical preparation ST
246 available from SIGA Technologies Inc. (USA), synthesized in NIOCH SB RAS by
the technique suggested by the authors. It was demonstrated that the compound
NIOCH-14 (7-[N'-(4-Trifluoromethylbenzoil)-hydrazidecarbonil]
tricyclo[3.2.2.02,4]non-8-en-6-carbonic acid) possessed comparable with ST-246
antiviral activity concerning EV and MPXV on all indicators used. Therefore, at
infection of mice with EV (strain K-1) and peroral administration of NIOCH-14 and
ST-246 in a dose 50 mkg/g of mouse weight (12-14 g) within 10 days the survival
rate and average life expectancy of mice authentically exceeded the control
levels. EV titers in lungs through 6 days after infection in the same groups were
lower than in the control. In addition to that, after 7 days of infection of mice
with MPXV (strain V79-1-005) and daily peroral administration of NIOCH-14 and ST
246 in a dose 60 mkg/g of mouse weight (9-11 g) authentic decrease in a part of
infected animals and MPXV titers in lungs was observed.
PMID- 24354065
TI - [Genetic characterization of the rabies virus field isolates detected in Russian
Federation within the period 2008-2011].
AB - Sixty-three gene N fragments of rabies virus field isolates detected within the
period 2008-2011 in different regions of Russian Federation were sequenced. The
comparison with previously tested isolates and strains has shown that newly
isolated isolates can be placed into five previously described phylogenetic
groups: Arctic group, Central Russian group, Eurasian group, Northern European
group, and Caucasian group. The Arctic group isolates detected in Komi republic
were identical to previously described rabies virus strain from Yakutia. This is
the first reliable case of detecting Arctic group rabies virus in European part
of Russia.
PMID- 24354066
TI - Ultrasound-guided procedures in anesthesia.
PMID- 24354067
TI - Response: Ultrasound-guided procedures in anesthesia.
PMID- 24354068
TI - Assessment of recent graduates preparedness for entry into practice.
AB - To date no studies have been conducted to assess the preparedness of CRNA
graduates for entry into practice by asking graduates and their respective
employers to assess specific competencies. The purpose of this study was to
assess recent graduates' preparation and performance. It was hypothesized recent
graduates are prepared for entry into nurse anesthesia practice. This study was
conducted between August 2011 and February 2012. An online survey tool was used
to rate graduates' preparedness to perform 17 professional competencies. Surveys
were distributed to 2349 CRNAs who graduated in 2009 and 2,663 employers who
hired recent graduates. A power of 90% for employers and 85% for graduates was
obtained (P = .05). Analysis of a sample size of 148 matched graduate-employer
pairs provided 88% power. Overall, 98% of the graduates and 97% of the employers
indicated graduates were prepared for practice. Of the 1,407 graduates assessed
by employers, 1,343 (96%) would be hired again. Competencies identified as
opportunities to enhance include administration of peripheral nerve blocks,
insertion of central lines, insertion of pulmonary artery (PA) catheters, and
chronic pain management techniques. The majority of employers rated these
competencies as not applicable in their practice setting. Results suggest recent
graduates are prepared and perform the competencies for entry into practice.
While graduates and employers identified opportunities to enhance preparation it
may not be sufficient to simply improve education without changing CRNA practice
expectations.
PMID- 24354069
TI - The revised scope of nurse anesthesia practice embodies the broad continuum of
nurse anesthesia services.
AB - The AANA determines the scope of nurse anesthesia practice. It is important for
all members to understand the scope of practice that governs their work to better
practice their profession and mentorship. In January 2013, the AANA Board of
Directors charged the Practice Committee to revise the Scope of Nurse Anesthesia
Practice. A systematic review of literature, focus groups, and a survey were
conducted. Major focus group themes were identified, and survey results were
analyzed to identify relationships between variables. The literature search
resulted in 8,739 abstracts. Forty-six articles were reviewed. Full scope of
advanced practice registered nurse (APRN) practice was a recurrent theme across
the literature. Focus group themes include: (1) elements of nurse anesthesia
practice; (2) future practice opportunities; (3) interprofessional collaboration;
(4) full scope of practice; (5) autonomous practice; and (6) barriers to practice
and recommendations. Of the 4,200 CRNA survey respondents, 44.6% are not
permitted to practice to their full scope of practice. The revised Scope of Nurse
Anesthesia Practice embodies the comprehensive span of nurse anesthesia practice.
PMID- 24354070
TI - A review of the evidence for active preoperative warming of adults undergoing
general anesthesia.
AB - Inadvertent perioperative hypothermia, a common occurrence in the operating
suite, is associated with many adverse outcomes. It is the nurse anesthetist's
goal to attenuate the incidence of this problem. Although active intraoperative
warming is a widely accepted practice, active preoperative warming may be a less
explored option for temperature maintenance. A search strategy to identify
systematic reviews and investigations in peer-reviewed journals was undertaken to
identify evidence examining the efficacy of preoperative warming. Evidence
sources meeting the search criteria were randomized controlled trials and a
cohort study using historical controls. Most of the studies support the
implementation of active preoperative warming by demonstrating that subjects were
warmer during the perioperative period. Overall, these differences were
statistically significant and likely clinically significant. Future clinical
trials should examine shorter warming times and lower warming unit settings,
should include appropriate sample sizes, and should consistently employ trained
staff using calibrated biometric instruments to measure temperature.
PMID- 24354071
TI - Impact of goal-directed perioperative fluid management in high-risk surgical
procedures: a literature review.
AB - Guidelines for the perioperative administration of fluid are often based on
static hemodynamic targets such as central venous pressure, and delayed volume
status indexes such as blood pressure, heart rate, capillary refill, and urine
output. Traditional fluid management protocols also rely heavily on algorithmic
estimates of fluid deficit, intravascular fluid volume status, fluid loss, and
basal fluid requirements to guide perioperative fluid administration. Such
formulaic approaches lack definitive physiologic endpoints for determining fluid
optimization and fail to address the roles of tissue oxygenation and end-organ
perfusion in achieving positive long-term patient outcomes. Recent advances in
hemodynamic monitoring have produced sophisticated dynamic measures of volume
status, such as stroke volume variation and pulse pressure variation, which may
serve as functional indexes for perioperative fluid administration. This article
reviews randomized controlled trials measuring the impact of perioperative goal
directed therapy on outcomes among patients undergoing high-risk surgical
procedures. A broad literature search was conducted, and 12 studies met the
inclusion criteria. Studies were evaluated for design, population, goal-directed
therapy targets, monitoring devices used, clinical endpoints, methods, and
results. Goal-directed therapy was associated with decreased hospital stay
compared with the control group (in 7 studies) and reduced number of
postoperative complications (7 studies).
PMID- 24354072
TI - Use of a left-sided double-lumen endotracheal tube in a patient with a prior left
pneumonectomy.
AB - A 77-year-old man, 7 years after left pneumonectomy, was scheduled for a right
upper pulmonary lobectomy. The early identification of a newly developing
carcinoma on the right upper pulmonary lobe warranted surgical resection. Right
exploratory thoracotomy, pleural lysis, partial pleurectomy, and right upper lobe
wedge resection were completed, and the patient was discharged without sequelae.
This case report describes the intraoperative anesthetic management of a right
upper lobe wedge resection and attributes the uneventful intraoperative outcome
to a strategically and skillfully placed left double-lumen endotracheal tube.
PMID- 24354073
TI - Anesthetic management of a patient with congenital insensitivity to pain: a case
report.
AB - Pain protects the body from damaging effects of harmful stimuli. Congenital
insensitivity to pain is a rare inherited disorder characterized by diminished or
absent sensitivity to pain, touch, and pressure that leads to frequent trauma and
self-mutilation. The disorder is part of the hereditary sensory and autonomic
neuropathy (HSAN) family, in which 5 types have been recognized. Research and
case reports of anesthetic risks and analgesic needs of these patients is limited
due to the infrequent nature of the disorder. Recommendations for anesthesia
include modification of intraoperative opioid requirements, use of anesthetics to
ensure cooperation and immobility, and intraoperative temperature monitoring. It
is imperative for anesthesia providers to understand which type of HSAN their
patient experiences and to conduct a thorough preoperative interview because a
different interpretation of sensory loss may occur in each HSAN category. This
article reports the case of a patient with HSAN type 2 who presented for knee
arthroscopy.
PMID- 24354074
TI - Development of an amygdalocentric neurocircuitry-reactive aggression theoretical
model of emergence delirium in posttraumatic stress disorder: an integrative
literature review.
AB - The purposes of this integrative literature review were to (1) present a synopsis
of current literature describing posttraumatic stress disorder (PTSD), the
amygdalocentric neurocircuitry, emergence delirium, reactive aggression, and the
interaction of general anesthetics and the amygdalocentric neurocircuitry; (2)
synthesize this evidence; and (3) develop a new theoretical model that can be
tested in future research studies. Over the past decade, a dramatic rise in PTSD
among veterans has been reported because of recent combat deployments. Modern
anesthetics alter the function of the amygdalocentric neurocircuitry to produce
amnesia and sedation. The etiology of emergence delirium is poorly understood,
and the condition is uncommon outside the pediatric population. Emergence
delirium among patients with PTSD, however, has been reported by military nurse
anesthetists. To date, there have been no scientific studies conducted to
identify the cause of emergence delirium in combat veterans with PTSD. This new
theoretical model may explain why noxious stimuli at the time of emergence may
stimulate the thalamus, leading to activation of an uninhibited amygdalocentric
neurocircuitry. Because of the loss of top-down inhibition, the hyperactive
amygdala then stimulates the hypothalamus, which is responsible for creating an
increase in excitatory activity in the unconscious patient, resulting in
emergence delirium.
PMID- 24354075
TI - Anesthetic implications of myasthenia gravis: a case report.
AB - Myasthenia gravis is an autoimmune neuromuscular disorder that causes the
destruction and overall decrease in functional acetylcholine receptors at the
neuromuscular junction. The resultant respiratory and cardiovascular implications
are a primary cause of mortality; therefore, a complete and comprehensive
understanding of this disorder is vital for the anesthesia provider. The case
presented demonstrates the anesthetic challenges involved, with a focus on the
overall approach, pharmacologic considerations, physiological changes, and an
emphasis on preoperative optimization.
PMID- 24354076
TI - A novel approach to improving the safety of patients undergoing lumbar
laminectomy.
AB - The anesthesiology field has recently embraced the use of checklists to obviate
the need for long-term memory, improve safety, and achieve goals and tasks. These
checklists serve to increase safety, improve consumer satisfaction, and reduce
mortality and morbidity. Spinal surgery with the patient lying prone is
associated with complex morbidities when there is inattention to proper
positioning technique. Problems arising from malpositioning of the patient
undergoing spinal surgery are attributed to body habitus and the body's contact
with specialized and complex operating room table frames. Common problems
associated with the prone position are brachial plexus injury, cervical spine
nerve injuries, and postoperative visual loss. The purpose of this research
project was to examine the use of a checklist for nurse anesthetists who provide
care for patients undergoing spinal surgery. The checklist addressed specific
positioning needs as a means of decreasing mortality and morbidity. It is
theorized that the use of a checklist will serve as a systematic aid to memory
and enable the anesthetist to adhere to proper positioning techniques in this
patient population and thereby improve outcomes.
PMID- 24354077
TI - Anesthetic management of a simultaneous emergency craniotomy and cesarean
delivery.
AB - Fetal heart tone monitoring is a frequently used tool during nonobstetric
maternal surgery to evaluate the immediate well-being of a fetus. We present a
case of a parturient requiring an emergency craniotomy, during which fetal heart
tone monitoring demonstrated fetal distress patterns. A simultaneous emergency
craniotomy and emergency cesarean delivery proceeded with favorable outcomes for
both mother and infant. We present several issues associated with managing an
emergent and concurrent maternal-fetal procedure.
PMID- 24354079
TI - Bring the vision to life.
PMID- 24354078
TI - AANA Journal Course: Update for nurse anesthetists--part-4--transcatheter aortic
valve replacement.
AB - Aortic stenosis is the most frequently acquired heart disease, and the prevalence
is rising because of the aging population. If the disease is left untreated,
survival in symptomatic patients averages only 2 to 3 years. Surgical aortic
valve replacement is the only definitive treatment, yet 30% of elderly patients
are not considered candidates because the presence of comorbidities makes the
risk of sternotomy and cardiopulmonary bypass prohibitively high. Transcatheter
aortic valve replacement (TAVR) is an innovative, high-tech, less invasive
alternative. The procedure is usually performed using general anesthesia and a
multidisciplinary team from interventional cardiology and cardiothoracic surgery
in a "hybrid" operating environment with advanced imaging capabilities. There are
2 major catheter-based approaches to the aortic valve: retrograde percutaneous
through the femoral artery and aorta or direct antegrade through a thoracotomy
and the left ventricular apex. Apnea and rapid ventricular pacing are used to
interrupt cardiac ejection during balloon valvuloplasty and prosthesis
implantation. The most significant complications include vascular damage, stroke,
paravalvular aortic insufficiency, and heart block. Outcomes studies comparing
TAVR with medical management demonstrate improved patient survival, functional
status, and quality of life. Currently TAVR is considered the treatment of choice
for patients who are not surgical candidates and is a proven alternative for high
risk surgical candidates.
PMID- 24354080
TI - Taking the lead.
PMID- 24354081
TI - Supporting unit-based leadership.
PMID- 24354082
TI - Gero council discusses ACA impact on Medicare.
PMID- 24354083
TI - [Does the inclusive mainstream public school eliminate the special education
school?].
PMID- 24354084
TI - [Medication administration in pediatrics: pitfalls and sources of error from the
viewpoint of nurses].
PMID- 24354085
TI - [Report of the 2nd Specialty Congress of Pediatric Intensive Care in Tubingen].
PMID- 24354086
TI - [Regional correlation between income deficit and hospital treatment in children].
PMID- 24354087
TI - [Sepsis in pediatrics].
PMID- 24354088
TI - [2013 BeKD Annual Congress: Science meets general practice and leads to practical
discussions].
PMID- 24354089
TI - [Germany's first pediatric hospice celebrates an anniversary].
PMID- 24354090
TI - [What is the energy thief called?].
PMID- 24354091
TI - [Florence Guinness Blake - progressive nursing pedagogue].
PMID- 24354092
TI - [Inclusion - the goal and the way].
PMID- 24354093
TI - The correlation between endothelin-1 levels and spirometry in dialysis patients
compared to healthy subjects.
AB - BACKGROUND AND AIM: Several studies demonstrated a six-fold increase in plasma
concentration of endothelin-1 (ET-1) in diaysis patients (hemodialysis and
peritoneal dialysis) compared to healthy control subjects. However, the effects
of ET-1 on respiratory function in these patients are less known. The aim of this
study was to determine the potential differences in spirometric values in
relation to ET-1 levels. METHODS: The study included 28 patients (15 male, 13
female, mean age 55.9 +/- 16. 2 years) with end stage renal diseases (ESRD)
receiving regular hemodialysis (HD), 23 patients (10 males, 13 females, mean age
55.8 +/- 15.8 years) with ESRD treated with continuous ambulatory peritoneal
dialysis (CAPD) without any cardiovascular or respiratory diseases, and 30
healthy volunteers (14 male, 16 female, mean age 51.8 +/- 15.6 years) in control
group. In each of the three groups the participants were divided into two
additional sub-groups according to the serum levels of ET-1. The spirometry
values were recorded before the onset of hemodialysis and prior to emptying the
peritoneal cavity in CAPD patients. The results were analyzed using standard
statistical methods (Student's t-test). RESULTS: Patients who were treated with
HD or CAPD were found to have significant difference in values of most pulmonary
function parameters between subjects with ET-1 levels lower than 6.6 pg/ml and
subjects with ET-1 levels higher than 6.6 pg/ml. In the control group there was
no difference in pulmonary function parameters in correlation with ET-1 levels.
ET-1 values in patients of both dialysis groups were significantly higher
compared to healthy subjects. CONCLUSIONS: Higher levels of ET-1 in dialysis
patients over healthy subjects is associated with lower parameters of lung
function tests. A possible pathophysiological mechanism for deterioration of
pulmonary function might be explained by progression of inflammation, pulmonary
oedema also known as "uraemic lung" or/and the progression of pulmonary
hypertension.
PMID- 24354094
TI - Cost of a population-based programme of chest x-ray screening for lung cancer.
AB - BACKGROUND: After the implementation of a population-based programme of chest x
ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was
significantly reduced. Analysis of the incremental costs due to this type of
screening programme is needed to evaluate its economic impact on the healthcare
system. METHODS: In July 1997 a population-based cohort, consisting of all high
risk smokers (n=5,815) identified among 60,000 adult residents from the Varese
province, was invited to a LC screening programme (an annual CXR for five years)
in a general practice setting, and was observed through 2006. Invitees received
National Health Service (NHS) usual care, with the addition of CXRs in screening
participants. At the end of observation, among the 245 LCs diagnosed in the
entire screening-invited cohort the observed LC deaths were 38 fewer than
expected. To estimate the incremental direct cost due to screening in the invited
cohort for the period July 1997-2006, we compared the direct cost of screening
administration, CXR screens and LC management in the invited cohort and in the
uninvited and unscreened controls in NHS usual care setting. RESULTS: Over the
9.5 years, the total incremental direct healthcare costs (including screening
organization/administration, CXR screens, additional procedures prompted by false
positive tests, overdiagnosed LCs) were estimated to range from euro 607,440 to
euro 618,370 (in euros as of 2012), equating to between euro 15,985- euro 16,273
per patient out of the 38 LC deaths averted. CONCLUSIONS: In a general practice
setting, the incremental cost for a CXR screening programme targeted at all high
risk smokers in a population of 60,000 adults was estimated to be about euro
65,000 per annum, approx. euro 16,000 for each LC death averted.
PMID- 24354095
TI - Pulmonary rehabilitation in lung cancer.
AB - Non-small-cell lung cancer (NSCLC) represents a very severe disease, being its
incidence increasingly reported and, nowadays, successfully treatable only when
surgery is deemed to be feasible. Furthermore, the disease and the clinical
effects related to the complementary therapies (radio and/or chemotherapy) may
strongly affect, frequently with dramatic clinical side effects, the patient's
ability to endure physical exercise. In such context, the PR(PR), which has
already been proved to be useful and effective in other diseases such as COPD,
could play a pivotal role. The aim of this review article is, therefore, to
analyze the pertinent data recently reported in English literature in order to
highlight the role of rehabilitation as complementary therapy in the management
of patients with NSCLC. The evidence currently available suggests that, when
surgery is indicated, PR is a safe and feasible option, both during pre-operative
and post-operative timing.The safety and feasibility of rehabilitation are proven
even in inoperable patients, although to date, little evidence has been reported
on its role in the overall management of such complex diseases.
PMID- 24354096
TI - Pleurodesis in the treatment of pneumothorax and pleural effusion.
AB - Malignant pleural effusion and persistent and/or recurrent spontaneous
pneumothorax are clinical entities requiring pleurodesis to avoid the
accumulation of liquid and air, respectively. The objectives are to alleviate
symptoms (dyspnea, pain and cough), decrease prolonged air leak, avoid recurrence
and improve quality of life. Chemical pleurodesis utilizes chemical irritants.
The most common of these is "talc" because of its efficiency and its success in
lowering the rate of recurrence. Its main indication is in the palliative
treatment of malignant pleural effusion. Other substances less frequently used
because they are rarely used currently or under study are cytostatics,
antibiotics, antiseptics and autologous blood. Surgical pleurodesis with
mechanical abrasion by videothoracoscopy is indicated primarily in the treatment
of spontaneous pneumothorax because it is highly efficient, easy to carry out,
and has low morbidity when compared to pleurectomy. Using pleurodesis in benign
effusion is highly controversial. Its principal indications are hepatic
hydrothorax, chylothorax, and cardiac effusion that does not respond to medical
treatment. Plasma determinations of systemic inflammatory markers and thoracic
ultrasound studies can evaluate the efficacy of pleurodesis. We do not recommend
the use of non-steroidal anti-inflammatory drugs in the postoperative period to
avoid the possibility of interfering with hemostasis or the formation of
adherences.
PMID- 24354097
TI - Osteophytes may be a rare cause of recurrent pleural effusions.
AB - We report a rare case of a 59 year-old female, who was admitted to the hospital
because of a recurrent right-sided pleural effusion. The initial work-up was non
diagnostic. The diagnosis was finally confirmed following medical thoracoscopy,
where an osteophyte of a rib was found to protrude sharply into the thoracic
cavity. Chronic inflammatory changes of the pleura suggested mechanical
irritation due to long lasting friction between this bony structure and the
underlying lung. This is the first report where an osteophyte seems to be
implicated in pleural pathology. A brief review of the available data from the
literature is presented to further support our results.
PMID- 24354098
TI - Extralobar pulmonary sequestration: a case report.
AB - We described the case of a 36-year-old Turkish female with an extralobar
pulmonary sequestration who suffered from chest and back pain for five years
without any evidence of pulmonary infection. A chest X-ray showed an area of
opacity behind the cardiac silhouette in the lower area of the left hemithorax. A
CT scan of the thorax with intravenous contrast showed a 9 x 7 cm in size ovoid
mass with necrosis in the lower left lobe. It revealed two aortic branches
directed toward the pulmonary opacity. She subsequently underwent surgery and the
anomalous tissue was removed by mass excision. The patient was diagnosed with
extralobar pulmonary sequestration.
PMID- 24354099
TI - Hyperventilation and seizures in an adolescent female.
AB - A 16 year-old girl was admitted after suffering from recurrent episodes of
dyspnea and stridor, cyanosis, loss of contact, stiffening of all four limbs,
clenching of the jaw and eye retroversion that lasted for a few seconds to a
minute, followed by slow recovery of consciousness without any loss of sphincter
control. These symptoms began at the age of 11 and worsened over time. Prolonged
rate corrected QT intervals was observed with an ECG. Two cardio-respiratory
monitorings were performed (one during daytime hours while the patient was awake,
and one at night time while the patient slept). Daytime recordings showed 17
central apnoeas and 97 central hypopneas, with an apnea-hypopnea index (AHI) of
13.2 events/hour, that were associated with severe oxyhemoglobin desaturation. In
contrast, night time recordings were normal (AHI=1.1 events/hour). The patient
underwent diurnal monitoring of transcutaneous pCO2(PtcCO2), transcutaneous
O2(PtcO2), SpO2 and end tidal CO2 (PETCO2), with simultaneous monitoring of
regional cerebral oxymetry (rSO2) which showed values of PtcCO2 between 8 and 15
mmHg, suggesting several episodes of marked hyperventilation. Twenty-nine
episodes of severe arterial desaturation (SpO2<50%) were registered, all after
the same number of apnea events, with ascent of PtcO2 up to 28 mmHg at the end of
apnea. During the final phase of apnea, the patient showed cyanosis, contact
disturbance, grimaces, oral movements of rhyme, and, on three occasions, partial
seizures. A mask was packaged and applied daytime to the face of the patient
during episodes of hyperventilation to prevent, together with a psychiatric
follow up, rapid falls of PaCO2 levels determining central apnoeas.
PMID- 24354100
TI - Pleural mesothelioma in a young male patient.
AB - We present the case of a 33-year-old male patient suffering from lymphocytic
pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a
malignant tumor of the pleura that is mainly caused by chronic exposure to
asbestos fibers and more than 40 years of exposure are needed to develop the
disease. Early studies on the relationship of asbestos and mesothelioma were
issued in the 1960s. Fibers migrate from the parenchyma of the lung to the
visceral pleura. It is widely known that asbestos is an oncogenic factor which
can cause damage to DNA. A chest x-ray may reveal pleural effusion with or
without pleural thickening, whereas a chest CT may also reveal pleural
thickening, uniform and/or lobular. Specific tests, such as immunohistochemical
staining, are used in order to help differential diagnosis. Extrapleural
pneumonectomy is used as a therapeutic option which involves removal of the lung
as well as both the visceral and parietal pleura, the affected part of the
pericardium and diaphragm. Surgery should be followed up by radiotherapy and
chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21
months. The case presented underlines that in the event of pleural effusion with
a lymphocyte type physicians should consider the possibility of a pleural
mesothelioma during differential diagnosis, even in relatively young patients.
PMID- 24354102
TI - Demystifying the DSM-5.
PMID- 24354101
TI - Health care volunteers strengthen New Jersey.
PMID- 24354103
TI - Raising awareness about human trafficking.
PMID- 24354104
TI - Magnetic resonance lymphography demonstrates spontaneous lymphatic disruption and
regeneration in obstructive lymphedema.
AB - The present study was aimed at observing both the damage and change process
undergone in lymphatic collectors in obstructive extremity lymphedema. Forty-five
patients with obstructive extremity lymphedema who had been examined with
magnetic resonance lymphangiography (MRL) were enrolled in the study. Among this
group, 36 were diagnosed with secondary lymphedema of the lower extremity and 9
exhibited upper extremity lymphedema after mastectomy. Morphological damage as a
result of obstruction of collecting lymph vessels was recorded and analyzed.
Obvious damage to the lymph vessels was found in all of the 36 lower extremity
lymphedema cases with different lengths of history, including vessel disruption
in 21 and lymphatic regeneration in 15. Lymphatic damage occurred in the anterior
tibial area of the lower leg in almost every case. In 9 cases with upper
extremity lymphedema, collecting lymphatic disruption and lymph tracer leakage
was seen in multiple patterns. Imaging displayed that ruptured lymph collectors
healed spontaneously or regenerated into a segment of the lymphatic network. The
present study provided real-time images of collecting lymphatic vessels in
obstructive lymphedema. These were seen to have undergone disruption, displayed
lymphorrhoea, and/or lymphatic regeneration. In addition, the images suggest that
the anterior tibial lymphatic is the weak point of the lymphatic pathway in the
lower limb.
PMID- 24354105
TI - A novel, validated method to quantify breast cancer-related lymphedema (BCRL)
following bilateral breast surgery.
AB - We sought to develop a formula to quantify breast cancer-related lymphedema
(BCRL) after bilateral breast surgery, which functions independently of the
contralateral arm and accounts for fluctuations in patient weight. Perometer arm
measurements from 265 unilateral breast surgery patients were analyzed. We
assessed the relationship between change in patient weight and contralateral arm
volume and developed a weight-adjusted volume change formula (WAC). The WAC
formula and previously-established RVC formula were compared for classification
of BCRL (> or = 10% volume increase) in unilateral breast surgery patients. We
then evaluated BCRL incidence using the WAC formula in 225 bilateral mastectomy
patients. Change in patient weight and contralateral arm volume demonstrated an
approximately linear relationship. Weight-adjusted arm volume change (WAC) was
therefore calculated as WAC = (A2*W1)/(W2*A1) - 1 where A1 is pre-operative and
A2 is post-operative arm volume, and W1, W2 are the patient's corresponding
weights. In the unilateral analysis, there was no significant difference in
number of patients classified as having BCRL using the RVC and WAC formulas (p =
0.65). In bilateral mastectomy patients 11.1% (25/225) developed BCRL, defined as
> or = 10% WAC. Independent risk factors for lymphedema included axillary lymph
node dissection (ALND) and higher pre-operative BMI (p<0.05). Use of this weight
adjusted arm volume change formula should be of value for quantification of BCRL
after bilateral breast surgery.
PMID- 24354106
TI - Dynamics of pleural fluid effusion and chylothorax in the fetus and newborn: role
of the lymphatic system.
AB - Pleural fluid effusion particularly chylothorax is a relatively rare occurrence
in the newborn, but when it occurs it is often life-threatening. In this article,
we describe and illustrate the morphologic features of the visceral and parietal
pleura including pleural lymphatics and the physiology and pathophysiology of
pleural fluid balance. The role and function of the lymphatic system in
controlling the volume and composition of pleural liquid are detailed and a
conceptual scheme presented. Finally, the crucial role of inadequate lymphatic
drainage (either functional overload from an imbalance in Starling forces or
mechanical insufficiency from lymphatic dysplasia) is emphasized.
PMID- 24354107
TI - L-dex ratio in detecting breast cancer-related lymphedema: reliability,
sensitivity, and specificity.
AB - Advances in bioelectrical impedance analysis (BIA) permit the assessment of
lymphedema by directly measuring lymph fluid changes. The objective of the study
was to examine the reliability, sensitivity, and specificity of cross-sectional
assessment of BIA in detecting lymphedema in a large metropolitan clinical
setting. BIA was used to measure lymph fluid changes. Limb volume by sequential
circumferential tape measurement was used to validate the presence of lymphedema.
Data were collected from 250 women, including healthy female adults, breast
cancer survivors with lymphedema, and those at risk for lymphedema. Reliability,
sensitivity, specificity and area under the ROC curve were estimated. BIA ratio,
as indicated by L-Dex ratio, was highly reliable among healthy women (ICC=0.99;
95% CI = 0.99 - 0.99), survivors at-risk for lymphedema (ICC=0.99; 95% CI = 0.99
0.99), and all women (ICC=0.85; 95% CI = 0.81 - 0.87); reliability was
acceptable for survivors with lymphedema (ICC=0.69; 95% CI = 0.54 to 0.80). The L
Dex ratio with a diagnostic cutoff of >+7.1 discriminated between at-risk breast
cancer survivors and those with lymphedema with 80% sensitivity and 90%
specificity (AUC=0.86). BIA ratio was significantly correlated with limb volume
by sequential circumferential tape measurement. Cross-sectional assessment of BIA
may have a role in clinical practice by adding confidence in detecting
lymphedema. It is important to note that using a cutoff of L-Dex ratio >+7.1
still misses 20% of true lymphedema cases, it is important for clinicians to
integrate other assessment methods (such as self-report, clinical observation, or
perometry) to ensure the accurate detection of lymphedema.
PMID- 24354108
TI - Predictive factors of response to phase I complete decongestive therapy in upper
extremity lymphedema following breast carcinoma in Iran.
AB - Post-mastectomy chronic lymphedema as a complication of breast cancer treatment
is primarily managed with Complete Decongestive Therapy (CDT). We examined
various factors for correlating with results of Phase I CDT treatment in
controlling the upper extremity lymphedema. Study population consisted of
patients with lymphedema referred to the Lymphedema Clinic of the Iranian Breast
Cancer Research Center for control of arm edema. After obtaining the demographic
and clinical data, patients were treated with CDT for 2 - 3 weeks. One hundred
and thirty seven patients (mean age +/- SD; 53.5 +/- 10 years) were studied. In
48.7% of patients, the affected arm was the dominant limb. Fifty percent of
patients experienced lymphedema during the first year after surgery, and mean
duration of lymphedema was 35 +/- 43 months. Mean volume reduction was 43% +/-
14.87% (p = 0.03). There was a significant relationship between the percent of
volume reduction and initial lymphedema volume (p=0.003) as well as duration of
lymphedema (p=0.002). Our results demonstrate that Phase I CDT treatment is very
effective for post mastectomy lymphedema, and particularly if it is provided in
earlier stages of disease. In addition, CDT also has an important role in
reducing clinical symptoms and improving limb function. In the appropriate
setting, Phase I CDT has been an effective method of controlling post mastectomy
lymphedema in this Iranian population.
PMID- 24354109
TI - Obesity and type 2 diabetes: epidemics that now require a population health
approach.
PMID- 24354110
TI - Validation of the urostomy education scale: the European experience.
AB - Bladder cancer is the fourth most common cancer among European males. Once
diagnosed with muscle invasive bladder cancer, a radical cystectomy is the first
line treatment, which results in a urostomy. The placement of a urostomy and the
care required impacts the patient's life. Previous research validated the
Urostomy Education Scale as the first standardized tool capable of documenting
the patients' level of stoma self-care skills and useful to guide patient
education interventions. A Danish-Dutch Fellowship was established to support and
provide further evidence of applicability of the Urostomy Education Scale.
PMID- 24354111
TI - Translating evidence into clinical practice adding to the evidence base:
validation of the urostomy education scale: the European experience.
PMID- 24354112
TI - A unique complication of urethral catheterization: pubic hair associated with
struvite bladder calculi.
AB - Bladder stones account for 5% of all urinary stone disease and can develop on a
foreign body, such as a misplaced suture, eroded surgical mesh, or ureteral
stent. In this case study, the authors present a patient with bladder stones
associated with pubic hairs introduced during a monthly indwelling Foley catheter
change. Clinicians have an important role in instructing patients on the use of
proper technique and hygiene practices during urethral catheterization to
minimize the potential for urinary complications.
PMID- 24354113
TI - Comparison of tolerability and adverse events following treatment with two GnRH
agonists in patients with advanced prostate cancer.
AB - This multicenter, randomized, crossover, open-label study (ClinicalTrials.gov
identifier: NCT01161563) assessed patients'and clinicians'perceptions of
injection site tolerability and adverse events following the intramuscular
injection of triptorelin pamoate or subcutaneous injection of leuprolide acetate
in 107 male, patients with advanced prostate cancer.
PMID- 24354114
TI - Urine specimen collection: how a multidisciplinary team improved patient outcomes
using best practices.
AB - The Institute of Medicine challenged the health care system to ensure safe care
for all patients. This article reviews one hospital's attempt to minimize
contamination of urine specimens by using a multidisciplinary team to implement
evidence-based best practices. The clinical nurse specialist (CNS) collaborated
with microbiology and laboratory personnel to review literature, collect and
analyze data, provide staff education, and facilitate change in urine collection
kits and urine processing that significantly improved the quality of urine
specimens in a 350-bed hospital in the Midwest.
PMID- 24354115
TI - Getting the intermittent catheter the patient needs: considerations in coding,
coverage and documentation.
PMID- 24354116
TI - Getting the intermittent catheter the patient needs: considerations in coding,
coverage and documentation. Author's response.
PMID- 24354117
TI - The role of informed consent in opioid prescribing.
PMID- 24354118
TI - Be aware of the risk of sudden cardiac arrest that killed Tony Soprano.
PMID- 24354119
TI - Opioid abuse puts physicians between a rock and a hard place but resources can
help them lead the debate on how to rein it in.
PMID- 24354120
TI - MSMS goes to bat for specialists to earn uplifts through BCBSM PGIP.
PMID- 24354121
TI - A lean, keen, problem-solving machine: Doctor Billi's dedication takes coalition
building & mentoring to new levels.
PMID- 24354122
TI - What to tell your patients about electronic health records.
PMID- 24354124
TI - Influenza sentinel surveillance: Michigan physicians needed for upcoming flu
season.
PMID- 24354123
TI - What's in a name?
PMID- 24354125
TI - How (and how not) to reform medical education.
PMID- 24354126
TI - [Dear Angels, goodbye. Goodbye to all that].
PMID- 24354127
TI - [Complications of the PICC in neurologic patients of the Hospital Ramon y Cajal].
AB - Descriptive study focused on the complications arising from the use of the PICC
(peripherally inserted central catheter) in a sample of patients admitted to the
neurology unit of the "Hospital Ramon y Cajal". After collecting and analyzing
the information about the sex and age of the patients, indication of implantation
of the PICC, thickness of the same, days of permanence, complications found,
cause of withdrawal of the catheter, and date of introduction and removal of the
same, we not found significant complications arising from the use of the same.
PICC is a safe and viable system for the administration of intravenous treatment
of long duration and nursing personnel is more qualified for which. This allows
the administration of intravenous treatment while preserving the vascular anatomy
of the patient, that is the purpose of all long-term catheters.
PMID- 24354128
TI - [Cyberbullying at school].
AB - The aim of this study is to known the prevalence of cyberbullying, and how these
students behave. We designed a transversal, descriptive and observational study
in two educative centers of Educacion Secundaria Obligatoria (ESO) in Toledo
(Spain). The sample comprised 190 students of both genders and ages between 11
and 16 years. Results indicated that 46.8% of the adolescents had been bullied by
Information and communication technology (ICT). The behaviors and communication
channels that are most frequently used to harass, have been offensive messages
through mobile and/or Internet and spreading rumors to harm the victim. It is
worth noting that almost a third of students harassed not request any help to
deal with it. The cyberbullying phenomenon is clearly established in our society
and a small percentage of cases it becomes a serious problem.
PMID- 24354129
TI - [Presence and characteristics of nursing terminology in Wikipedia].
AB - OBJECTIVE: To determine the presence and consultations with nurse terminology in
the Spanish edition of Wikipedia, and to analyze the differences with the English
edition. METHOD: We confirmed the existence of terminology via the Internet by
the access to the Spanish and English editions of Wikipedia. RESULTS: We
calculated the study sample (n = 386) from the 1840 nursery terms. 337 were found
in the Spanish edition and 350 in the English. We found significant differences
between the two editions (p < 0.001). Also differences were winched on to the
number of references in terms (p < 0.001). However, there were not differences in
the update/obsolescence of information, neither in the number of queries.
CONCLUSIONS: The entries (articles) on nursing terminology in the Spanish edition
of Wikipedia, has not yet reached an optimum level. Differences between Spanish
and English editions of Wikipedia are more related to term existence than
adequacy of information.
PMID- 24354130
TI - [Advanced nursing practice: development of an emerging model].
AB - AIM: To describe the historical evolution of Advanced Practice Nursing (APN) in
the international arena, and to describe the characteristics and competencies of
this nursing role, with the ultimate aim of encouraging reflection on the
implementation of this model of nursing in the Spanish context. METHODS: A
literature review in the databases CINAHL, MEDLINE and CUIDEN was conducted. In
addition, several websites were reviewed. RESULTS: At the international level,
there is evidence on the impact of the APN in the healthcare system, reducing the
number and length of hospital stays and showing greater user satisfaction.
Regarding the national context, it is clear the interest on this issue, although
the implementation of this advanced practice role is a pending matter.
CONCLUSIONS: In Spain, the implementation of the APN is a challenge due to the
legislative, educational, organizational and political factors that are involved
in the official introduction of this new nursing model.
PMID- 24354131
TI - [Assessment of acute postoperative pain in patients undergoing midline
laparotomy].
AB - OBJECTIVE: TO asses the prevalence and intensity of acute postoperative pain
(APP) in patients undergoing midline laparotomy in the first 24 hours after
surgery. METHOD: Cross-sectional study of prevalence. By a daily visit to the
unit of resuscitation we proceeded to the collection of data from patients who
met the inclusion criteria, providing prior information to obtain the consent.
Two valuations were realized by visual analog scale (VAS), the intensity of
postoperative pain at the time of the survey, coinciding with 24 postoperatory
hours, and the maximum of pain referred in the previous 24 hours. RESULTS: We
included seventy-three adultpatients undergoing midline laporotomy. The VAS score
at the time of the survey within 24 hours post-surgery was 2.01 (DE 2.29) and
4.43 (DE 3.77) as a result of the assessment of the maximum referred pain during
their stay in the unit. It was observed a negative correlation with age and the
VAS score in both the 24 hours (P = 0.025) and the one referred to the maximum
pain (P = 0.011). Scheduled based analgesia showed an important difference in VAS
scores in patients treated with dexketoprofen. CONCLUSIONS: It is concluded the
need for improvement in the care of patients with accute postoperative pain and
the need for revision of analgesic protocols. It is also necessary to protocolize
the use of VAS in units of resuscitation in a systematic way.
PMID- 24354132
TI - [Postoperative pain management using elastomeric pumps].
AB - Elastomeric infusions pumps are single use devices that permit continuous drugs
infusion in a safe and simple way. They help to maintain drugs plasma level
stability and analgesia in order to control acute pain and improves patients
quality of life, which are an effective alternative for de treatment of pain.
PMID- 24354133
TI - [Clinical simulation as a training tool for clinical teams and care change
facilitator].
AB - OBJECTIVE: The objective of this article is to describe and show the results of a
simulation training interprofesional program to meet a training need of Surgical
area professionals in management in cardiovascular surgery emergencies in
Valdecilla Hospital. MATERIAL: The activity was aimed to train at the 42 nurses
in rotation in the surgical area, nursing assistances, cardiovascular surgeons
and anesthetists. For it was made a study of the training needs and were designed
clinical simulation escenarios, theoretical sessions as well in workshops usual
workplace. RESULTS: The training project was conducted in four phases between May
21 to June 18, 2012, within which were 3 clinical cases for multidisciplinary
training in emergency usual CCV. With the full participation of 65 professionals
and 17 instructors, after further analysis to cases, results were achieved
improved teamwork, and picked up, several changes to be made in the organization
of the service. CONCLUSIONS: Clinical simulation mode responds to adult learning,
based on their own experience and personal reflection, and all in an environment
that does not risk to patients or professionals. It is really helpful and
flexible to meet different institutional challenges and where participants
highlighted two key aspects in this activity such as the multidisciplinary team
where they could train the professional standard and the possibility of analysis
and reflection after the event to share experiences and look for areas of
improvement among all the clinical team.
PMID- 24354134
TI - [The presence of ROL is very necessary for the development and the empowerment of
nursing science].
PMID- 24354135
TI - [Health status of the elderly population].
PMID- 24354136
TI - Thoughts on money and health care.
PMID- 24354137
TI - Physician executive compensation recovers with economy: s-l-o-w-l-y. Single
digit, two-year growth rates reported for most titles.
PMID- 24354138
TI - Major health care purchasers demand change.
PMID- 24354139
TI - Leading effective change in physician compensation and practice coverage.
PMID- 24354141
TI - Physician-led intervention improves critical care documentation and
reimbursement.
PMID- 24354140
TI - Critical management tools for getting costs under control.
PMID- 24354142
TI - Indexing performance measures.
PMID- 24354143
TI - Smoothing the transition from resident to attending physician using mentors.
PMID- 24354144
TI - Facilitating enduring-significant-quick (ESQ) change.
PMID- 24354145
TI - Conflict management in the health care workplace.
PMID- 24354146
TI - Mediation offers less costly way to resolve disputes.
PMID- 24354148
TI - Affordable Care Act: strategies to tame the future.
PMID- 24354147
TI - The Affordable Care Act: an annotated timeline.
PMID- 24354149
TI - The Affordable Care Act and electronic health care records. Does today's
technology support the vision of a paperless health care system?
PMID- 24354150
TI - Oral and maxillofacial pathology case of the month. Melanoma in situ (mucosal
lentiginous melanoma).
PMID- 24354151
TI - Save dentistry! Take a colleague to lunch.
PMID- 24354152
TI - President's message.
PMID- 24354153
TI - 83rd legislative summary.
PMID- 24354154
TI - View from the capitol.
PMID- 24354155
TI - TDA testifies in support of patient protection and safety--House Bill 1480.
PMID- 24354156
TI - Practice models in Texas.
PMID- 24354157
TI - The Texas State Board of Dental Examiners--regulating the profession.
PMID- 24354158
TI - Making an impression.
PMID- 24354159
TI - Dental Quality Alliance: measuring quality in dentistry.
PMID- 24354160
TI - National update: ADA council on governmental affairs.
PMID- 24354161
TI - The ACA impact on Texas dentists.
PMID- 24354162
TI - Medicaid and the children's health insurance program.
PMID- 24354163
TI - Change exchange. Pocket change for political change.
PMID- 24354164
TI - ADPAC speaks softly.
PMID- 24354165
TI - The voice of dentistry in Texas.
PMID- 24354166
TI - Remineralizng agents with casein phosphoprotein-amorphous calcium phosphate (CPP
AP) can promote white spot regression for orthodontic patients UT Cat# 2512.
PMID- 24354167
TI - Using CAD/CAM technology to create a 10-unit zirconia fixed partial denture--a
UTHSCSA dental school case report.
AB - From diagnosis and treatment planning to the materials being used, technology is
changing dentistry. New materials are providing dentists greater options for
treatment, while technology is streamlining the workflow in the office and dental
laboratory. Traditionally the creation of a long-span fixed partial denture was a
labor intense project--from waxing up the prosthesis--to stacking of the
porecelain. For larger frameworks, it was recommended for the dentist to bring in
the patient in for a framework try-in. However, advances in both CAD/CAM
technology and dental materials are revolutionizing the way dentistry is being
done. The following describes the fabrication of a 10-unit full contour zirconia
fixed partial denture completed in the pre-doctorate program at UTHSCSA Dental
School.
PMID- 24354168
TI - A comparison of facebow and dentofacial analyzer mountings.
AB - AIM: This investigation compared the accuracy and reliability of one arbitrary
facebow (4000 FB Pana -Mount) to the recently introduced "Dento-Facial Analyzer"
(4300 FB Kois) for locating and trasferring the hinge axis to articulator. A
kinematically located transverse horizontal axis provided the reference. MATERIAL
AND METHODS: Fourteen subjects, 9 female and 5 male, and 3 types of facebows were
utilized in this study. One orientation record was made with each of 3
instruments to mount 1 pindexed maxillary cast 3 times for each subject on the
same articulator. In order to measure the distance from articulator's hinge axis
to first molar bilaterally; a small nail was inserted in the stone cast in the
area of the first molar on both sides. A small indentation on the hinge axis of
the articlator served as the second reference point. A 6-inch/150 mm digital
caliper was used for measuring the distance between these points with an accuracy
of 0.03 mm and resolution of 0.01 mm. Four repeat measurements were done on both
sides of each mounted cast and averaged. RESULTS: The arbitrary earbow recorded
the hinge axis closer to the kinematic axis (within 4.18 mm on the right side and
3.57 mm on the left side) with smaller standard deviation compared to the Dento
Facial Analyzer (5.58 mm on the righ side and 5.72 mm on the left side).
CONCLUSION: The arbitrary facebow was found to be more accurate as compared to
the Dento-Facial Analyzer for reliability and accuracy and may serve better when
occlusal function is a primary concern. CLINICAL IMPLICATION: The simplicity of
the use of Dento-Facial Analyzer did not improve the accuracy of mounting the
maxillary cast onto the articulator. As a result it should be used in the clinic
cautiously.
PMID- 24354169
TI - Simplifying and improving soft-tissue management for fixed-prosthodontic
impressions.
AB - It is apparent that conventional impressions, usually made in vinyl polysiloxane
or polyether material, could be better. One of the significant reasons for
impressions' inadequacy is incomplete inclusion of the tooth preparation margins
in the impression. There are numerous reasons for this challenge, some of which
could be overcome by implementing the technique changes I have described in this
column.
PMID- 24354170
TI - Value for your profession. Staff education as a wise investment.
PMID- 24354171
TI - Guaiol--a naturally occurring insecticidal sesquiterpene.
AB - The dichloromethane fraction of Ferula ferulaeoides was analyzed by GC and GC-MS,
and thirty-four compounds were identified. The main component in the fraction,
guaiol (37.0%) was separated by chromatographic methods and identified from
spectroscopic data, including 1H and 13C NMR, and X-ray crystallographic
diffraction. Guaiol showed significant inhibition of aphids at a concentration of
70 mg/L. It also showed good contact activities against the 4th instar larvae of
Mythimna separate and 3rd instar larvae of Plutella xylostella, with LD50 values
of 0.07 and 8.9 mg/larva, as well as fumigation activity against the 4th instar
larvae ofM. separata and adult Musca domestica, with LC50 values of 3.5 microL/L
and 16.9 microL/L, respectively.
PMID- 24354172
TI - 3-oxoabolene and 1-oxocurcuphenol, aromatic bisabolanes from the sponge
Myrmekioderma sp.
AB - Two new aromatic bisabolane sesquiterpenes possessing an oxo functionality on the
prenyl chain, (+)-3-oxoabolene (3) and (+)-l-oxocurcuphenol (4), along with two
known sesquiterpenes, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated
from the sponge Myrmekioderma sp. The antiproliferative activity of 2-4 was
determined and showed an interesting selectivity; i.e., a good activity against
HT-29 cells with IC50s in the microM range, but a weak and incalculable toxicity
against Hela and normal fibroblast cells.
PMID- 24354173
TI - Acanthoic acid inhibits melanogenesis through tyrosinase downregulation and
melanogenic gene expression in B16 melanoma cells.
AB - The aim of this study was to investigate the in vitro inhibitory effects of
acanthoic acid (ACAN), isolated from Acanthopanax koreanum, on melanogenesis and
its related enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and
TRP-2 in B16 melanoma cells. We found that ACAN significantly attenuates melanin
synthesis and reduces the activity of intracellular tyrosinase, the rate-limiting
melanogenic enzyme. Western blot analysis showed that ACAN also decreases
tyrosinase, TRP-1, and TRP-2 protein expression. In addition, ACAN significantly
decreased the expression of microphthalmia-associated transcription factor
(MITF), a key regulator of melanogenesis. These results indicate that ACAN
effectively inhibits melanin biosynthesis through down-regulation of MITF and
thus could be useful as a new skin-whitening agent.
PMID- 24354174
TI - Cembranoids from the cultured soft coral Sinularia gibberosa.
AB - An EtOAc extract of the cultured soft coral Sinularia gibberosa yielded a new
cembrane-based diterpenoid, cugibberosene A (1), together with the previously
reported three cembranoids (2-4). The structure determination was based on
extensive NMR studies. The cytotoxic and antibacterial activities of
theseisolated metabolites 1-4 were evaluated in vitro.
PMID- 24354175
TI - Major constituents of Boswellia carteri resin exhibit cyclooxygenase enzyme
inhibition and antiproliferative activity.
AB - Aromatic gum from Boswellia carteri (olibanum oleogum) has long been used in
Egyptian traditional medicine. Cyclooxygenase-1 (COX-1) enzyme inhibitory assay
guided purification of the extracts of this resin resulted in five bioactive
compounds, 3alpha-O-acetyl-8,24-dien-tirucallic acid (1), verticilla-4(20),7,11
triene (2), cembrene A (3), incensole acetate (4), and incensole (5). The pure
isolates were investigated for their inhibitory effects on COX-1 and -2 enzymes
and human tumor cell lines Hep-G2, MCF-7 and RAW 264.7. Compounds 1-5 inhibited
COX-2 enzyme by 39.0, 32.7, 60.0, 46.3, and 49.8%, respectively. Furthermore,
compound 2 showed an inhibitory concentration of 50% (IC50) at 9 microg/mL
against Hep-G2 tumor cell line. This is the first report of COX-1 and -2 enzyme
and tumor cell proliferation inhibitory effects of compounds 1 and 2.
PMID- 24354176
TI - Cucurbitane-type triterpenes from Citrullus lanatus (watermelon) seeds.
AB - Two new cucurbitane-type triterpenes, 24-hydroperoxycucurbita-5,25-dien-3beta-ol
(1) and 25-hydroperoxycucurbita-5,23-dien-3beta-ol (2), were isolated from a MeOH
extract of Citrullus lanatus seeds. Compounds 1 and 2 exhibited moderate
cytotoxic activities with IC50 values of 33.4-52.4 microM against HL-60 (human
leukemia), P388 (murine leukemia), and L1210 (murine leukemia) cells. Compound 1
showed melanogenesis inhibitory activity (melanin content 80.0 %) with low
cytotoxicity (cell viability 97.6%) at a low concentration (10 microM).
PMID- 24354177
TI - A new taraxerol derivative from the roots of Microcos tomentosa.
AB - A new 3beta-O-vanilloyl-taraxerol, microcisin (1) and eight known compounds,
3beta-taraxerol acetate (2), 3beta-taraxerol (3), cholest-4-en-3-one (4), cholest
4-en-6beta-ol-3-one (5), beta-sitosterol (6), 7-hydroxycadalene (7), mellein (8)
and vanillin (9), were isolated from the roots of Microcos tomentosa. The
structures were determined by extensive analysis of their spectroscopic data. All
isolated compounds were evaluated for their cytotoxicity against KB and HeLa
cells.
PMID- 24354178
TI - Two new triterpenoids from Gelsemium elegans and Aglaia odorata.
AB - Eleganoside A (1) and odoratanone A (15), a triterpenoid trisaccharide glycoside
and a nortriterpenoid, together with twelve known compounds (2-13) and a mixture
of cerebrosides (14) were isolated from Gelsemium elegans and Aglaia odorata.
Their structures were elucidated by extensive spectroscopic and spectrometric
analysis. Eleganoside A (1) features a 3-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D
glucopyranosyl (1-->4)-beta-D-glucopyranoside of a peculiar 3,16-dihydroxyl
lanosta-8,24-dien-26-oic acid triterpenoid skeleton, and odoratanone A (15) is a
29-norcycloartane-type triterpenoid bearing an unusual five-membered methyl
acetal ring. Anti-acetylcholinesterase/butyrylcholinesterase (AChE/BChE) assay
indicated that at 50 microM, ethyl caffeate (5) was promising as a dual inhibitor
of AChE and BChE, and paeonol (3) and 24-hydroperoxy-24-vinylcholesterol (9)
exhibited BChE-selective inhibition.
PMID- 24354180
TI - Anticholinesterase and antioxidant activities of fucoxanthin purified from the
microalga Phaeodactylum tricornutum.
AB - Hot extraction with acetone was the most efficient method for the extraction of
fucoxanthin from Phaeodactylum tricornutum. The purified compound resulted in
three main peaks consisted of the trans form along with two isomers. The
structure of microalgal fucoxanthin was similar to that of brown seaweed, but the
ratio of trans- to cis-form was different. The ratio of the cis-form increased as
the extraction temperature increased. Fucoxanthin was unstable at high
temperature, in acidic condition, and after long period of storage. Fucoxanthin
exhibited strong activity against BChE, with an IC50 value of 1.97 mM and mixed
inhibition type, whereas it had weak activity against AChE. The IC50 value on
reducing power was 0.01 mM, which was much stronger than those of the positive
controls. When the amount of cis-isomer increased by 2%, the scavenging activity
against DPPH, hydrogen peroxide, superoxide anion, and reducing power decreased
by 21.0, 10.3, 16.0, and 19.7%, respectively. Therefore, fucoxanthin could be a
useful approach for Alzheimer's disease treatment.
PMID- 24354179
TI - Inhibition of tumor cells multidrug resistance by cucumarioside A2-2, frondoside
A and their complexes with cholesterol.
AB - In non-cytotoxic concentrations, frondoside A (1) from the sea cucumber Cucumaria
okhotensis and cucumarioside A2-2 (2) from C. japonica, as well as their
complexes with cholesterol block the activity of membrane transport P
glycoprotein in cells of the ascite form of mouse Ehrlich carcinoma. They prevent
in this way an efflux of fluorescent probe Calcein from the cells. Since the
blocking of P-glycoprotein activity results in decrease of multidrug resistance,
these glycosides and their complexes with cholesterol may be considered as
potential inhibitors of multidrug resistance of tumor cells.
PMID- 24354181
TI - Impact of ploidy change on secondary metabolites and photochemical efficiency in
Solanum bulbocastanum.
AB - Plants are well known for producing a wide diversity of natural compounds and
several strategies have been proposed to enhance their production. Among them,
somatic chromosome doubling may represent an effective and inexpensive method.
The objective of the current study was to investigate the effect of
polyploidization on the leaf metabolic profile and content of tetraploids
produced from a wild diploid (2n=2x=24) potato species, Solanum bulbocastanum
Dun. Photochemical efficiency of tetraploids was also analyzed. Results from HPLC
DAD and LC/MS analyses provided evidence that tetraploid genotypes displayed
either a similar or a lower phenylpropanoids, tryptophan, tyrosine and a
chaconine content compared with the diploid parent. Similarly, no significant
differences were found among genotypes both for measures of gas and for
chlorophyll fluorescence, except for non-photochemical quenching (NPQ). Steroidal
saponins content revealed superiority of some tetraploids with respect to the
diploid parent, suggesting perturbations in the mechanism regulating the
biosynthesis of such compounds following polyploidization. Lack of superiority
may be attributed to the time required for adjustment, adaptation and evolution
after the genomic shock induced by polyploidization, as well as the fact that an
optimum ploidy level for each species may be crucial. Our results suggest that
polyploidization as a strategy to enhance metabolite production cannot be
generalized.
PMID- 24354182
TI - Alkaloids from an endophytic streptomyces sp. YIM66017.
AB - Three alkaloids, flavensomycinoic acid (1), a linear polyketide, alpiniamide (2),
and cyclo (L-Trp-L-Ala) (3), were isolated from the culture filtrate of
endophytic Streptomyces sp. YIM66017 from Alpinia oxyphylla. Their structures
were elucidated by spectroscopic analysis and the structure of 1 was confirmed by
X-ray crystallographic analysis. Compound 1 was isolated from a natural source
for the first time, and compound 2 is a new compound. Compound 1 showed
cytotoxicity to MCF-7 with an IC50 value of 17.0 microM.
PMID- 24354183
TI - Novel decaturin alkaloids from the marine-derived fungus Penicillium oxalicum.
AB - From the mycelia of Penicillium oxalicum two new compounds, decaturins E (1) and
F (2), have been isolated, along with four known analogues, decaturin A (3),
decaturin C (4), decaturin D (5), and oxalicine B (6). The structures were
determined by HR-ESI-MS and 1D and 2D NMR analysis.
PMID- 24354184
TI - Monanchomycalin C, a new pentacyclic guanidine alkaloid from the far-eastern
marine sponge Monanchora pulchra.
AB - A new pentacyclic guanidine alkaloid, monanchomycalin C (1), along with the
earlier known ptilomycalin A (2), were isolated from the Far-Eastern marine
sponge Monanchora pulchra. The structure of 1 was elucidated using 1D and 2D NMR
spectroscopic and ma ss spectrometric da ta. Compounds 1 and 2 exhibited
cytotoxic activities against human breast cancer MDA-MB-231 cells with IC50
values of 8.2 microM and 4.3 pM, respectively.
PMID- 24354185
TI - Antiinflammatory and antioxidant flavonoids from Helichrysum kraussii and H.
odoratissimum flowers.
AB - Organic extracts of the flowers of Helichrysum kraussii and H. odoratissimum
contain several bioactive flavonoids, characterized by 'H NMR, '3C NMR and mass
spectrometry. Four flavonoids, 5,6-dihydroxy-3,7,8-trimethoxyflavone, 5,7
dihydroxy-3-methoxyflavone, 3',4',5,7-tetrahydroxy-3-methoxyflavone and 3',4',3,5
tetrahydroxy-7-methoxyflavone, have antioxidant activity by the DPPH free radical
assay, while 5,6-dihydroxy-3,7,8-trimethoxyflavone and 3',4',3,5-tetrahydroxy-7
methoxyflavone have promising anti-inflammatory activity.
PMID- 24354186
TI - Antiproliferative effect of flavonoids from the halophyte Vitex rotundifolia on
human cancer cells.
AB - Three flavonoids, luteolin (1), vitexicarpin (2) and artemetin (3), from the salt
marsh plant Vitex rotundifolia, were tested for their anti-proliferative
activities in AGS, MCF-7 and HT-29 human cancer cell lines and compared with the
control using MTT assay. Among them, 2 was most effective with an IC50 of 6.9 and
22.8 microM against AGS and HT-29 cells, respectively. Inaddition, mRNA
expression levels of major apoptosis-related genes such as p21, p53, Bcl-2 andBax
in AGS cells were evaluated by reverse-transcription polymerase chain reaction
(RT-PCR). Compound 2 not only enhanced most remarkably the expression level of
tumor suppressor genes p53 and p21, and pro-apoptotic gene Bax at a concentration
of 25 microM, but also suppressed the expression level of antiapoptotic gene Bcl
2 to 20% at the same concentration, thus shifting the Bax/Bcl-2 ratio in favor of
apoptosis.
PMID- 24354187
TI - Identification of a xanthine oxidase-inhibitory component from Sophora flavescens
using NMR-based metabolomics.
AB - We demonstrate that NMR-based metabolomics studies can be used to identify
xanthine oxidase-inhibitory compounds in the diethyl ether soluble fraction
prepared from a methanolic extract of Sophora flavescens. Loading plot analysis,
accompanied by direct comparison of 1H NMR spectraexhibiting characteristic
signals, identified compounds exhibiting inhibitory activity. NMR analysis
indicated that these characteristic signals were attributed to flavanones such as
sophoraflavanone G and kurarinone. Sophoraflavanone G showed inhibitory activity
towards xanthine oxidase in an in vitro assay.
PMID- 24354188
TI - Flavone C-glycosides from Lychnis senno and their antioxidative activity.
AB - A new flavone C-glycoside, 5-O-acetyl-2"-alpha-rhamnopyranosylisovitexin (1), was
isolated from the aerial parts of Lychnis senno Siebold et Zucc. (Family
Caryophyllaceae), along with 2"-alpha-rhamnopyranosylisovitexin (2), 2"-a
rhamnopyranosylisoorientin (3) and isoorientin 3'-mehyl ether (4). All these
compounds were isolated for the first time from L. senno and their antioxidative
activity was analyzed by the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic
acid) diammonium salt (ABTS) radical-scavenging method. Compound 3 showed
moderate antioxidative activity.
PMID- 24354189
TI - Anti-oxidative and DNA protecting effects of flavonoids-rich Scutellaria
lateriflora.
AB - Scutellaria lateriflora (American skullcap), a native plant of North America, has
been used by Americans and Europeans as a nerve tonic for more than 200 years. In
vivo studies have shown anxiolytic activity ofS. lateriflora in animals and
humans. However, the neuroprotective mechanisms ofS. lateriflora are not fully
understood. Oxidative stress plays a vital role in the neurodegenerative and
neuropsychiatric diseases such as anxiety, Alzheimer's disease, depression, and
Parkinson's disease. Bioactive compounds present in various medicinal plants
neutralize or scavenge toxic free radicals and thus suppress oxidative stress.
Therefore, the objective of this study was to investigate the antioxidant effects
of S. lateriflora. The antioxidant potential of aqueous or ethanolic extracts of
S. lateriflora was determined in mouse brain tissue using various biochemical
assays. Protective effects of S. lateriflora against oxidative stress induced DNA
fragmentation was determined using plasmid DNA. The ethanolic and aqueous
extracts scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The
ethanolic extract reduced tert-butyl peroxide-induced reactive oxygen species
(ROS) and lipid peroxides in the mouse brain homogenates. Furthermore, the
ethanolic extract of S. lateriflora protected hydrogen peroxide-UV induced
cleavage of supercoiled plasmid DNA. In conclusion, S. lateriflora exhibited
significant antioxidant effects. The current findings posit S. lateriflora as one
of the potential experimental herbal drugs that should be screened for its
therapeutic potential against various oxidative stress associated mental
disorders.
PMID- 24354190
TI - Polyphenolic compounds from callus cultures of Iris pseudacorus.
AB - A callus culture of Iris pseudacorus L. (Iridaceae) was established from plant
leaves using a modified Murashige and Skoog medium. A derivative of cinnamic acid
(lavandoside) (1), a neolignan (dehydrodiconiferyl alcohol-4-O-beta-D
glucopyranoside) (2) as well as three isoflavonoids, tectoridin (3), tectorigenin
(4), and iristectorigenin A (5) were isolated from the callus culture. Under
normal conditions, the calli accumulated 0.4% DW of polyphenols. The addition of
phenylalanine to a concentration of 1 mM resulted in a 1.5-fold increase in
isoflavonoid production, allowing the accumulation of 0.69% of polyphenols in the
callus dry weight. Tectorigenin, a promising chemotherapeutic and chemopreventive
agent for the treatment of carcinomas, was produced in I. pseudacorus calli in
high quantities (0.3% DW).
PMID- 24354191
TI - Pterocarpans from the root bark of Aeschynomene fascicularis.
AB - A new pterocarpan, aeschynocarpin (1), and the known pterocarpan 2
methoxymedicarpin (2) were isolated for the first time from Aeschynomene
fascicularis (Fabaceae) and their structures elucidated by means of spectroscopic
{UV/Vis, IR, and NMR (1H, 13C, COSY, HMQC,and HMBC)} andmass spectrometric (EI-MS
and HRCIMS) techniques. Both compounds were tested in vitro for their cytotoxic
and antiproliferative activities against a panel of cancer cell lines. This is
the first report on the presence of pterocarpans in the genus Aeschynomene.
PMID- 24354192
TI - Cytotoxic constituents of Pachyrhizus tuberosus from Peruvian amazon.
AB - Investigations into the chemical constituents of the seeds of the neglected tuber
crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven
components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2),
erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin
[pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were
isolated using several chromatography techniques and characterized and verified
by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic
effects of the methanolic P. tuberosus extract and isolated compounds in two
human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non
transformed human fibroblasts (MRC-5); IC50 values were calculated. The
methanolic P. tuberosus extract displayed respectable cytotoxic effects against
HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 microg/mL, respectively.
Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the
cancer cell lines tested, yielding IC50 values of 0.3 microg/mL against both MCF
7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts.
Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8
microg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5
mirog/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy
of further antitumor investigation.
PMID- 24354193
TI - (+)-rumphiin and polyalthurea, new compounds from the stems of Polyalthia
rumphii.
AB - Two new compounds, (+)-rumphiin (3) and polyalthurea (7), together with seven
known ones, 3,4,5-trimethoxy benzoic acid (1), (-)-seselinone (2), cannabisin D
(4), allantoin (5), oxostephanine (6) and a mixture of beta-sitosterol (8) and
stigmasterol (9) were isolated from the stems of Polyalthia rumphii. The chemical
structures of 3 and 7 were elucidated by the combination of spectroscopic data,
and the absolute configuration of 3 at C-2 was determined by the matrix method to
be R. All compounds were evaluated for their cytotoxicity on four human cancer
cell lines, which demonstrated that 3 was a moderate bioactive lignan, and 6
showed significant anticancer activity against SPC-A-1 and BEL-7402 cell lines
with IC50 values of 1.47 and 1.73 microg/mL, respectively.
PMID- 24354194
TI - Citriquinones A and B, new benzoquinones from Penicillium citrinum.
AB - Two new benzoquinones, citriquinone A (1) and B (2), were isolated from the
methanol extract of a soil fungus, Penicillium citrinum. The structures of the
new compounds were determined on the basis of detailed spectroscopic analysis.
Citriquinone A (1) exhibited antibacterial activity against Bacillus sp. and cell
migration inhibitory activity (CMIA) against human cancer cell line HEp 2.
PMID- 24354195
TI - Potent microbial and tyrosinase inhibitors from stem bark of Bauhinia rufescens
(Fabaceae).
AB - The stem bark extracts of Bauhinia rufescens Lam. (Fabaceae) yielded 6-methoxy-7
methyl-8-hydroxydibenz[b,f]oxepin, alpha-amyrin acetate, beta-sitosterol 3-O-beta
D-xylopyranoside, 4-(2'-Hydroxyphenethyl)-5-methoxy-2-methylphenol, menisdaurin
and sequoyitol. Their structures were determined using spectroscopic methods and
comparisons with the literature data. For the antimicrobial assay Gram-positive
and Gram-negative bacterial and fungal strains were tested, while the tyrosinase
inhibition assay utilized L-DOPA as a substrate for the tyrosinase enzyme. 6
Methoxy-7-methyl-8-hydroxydibenz[b,f]oxepin, a-amyrin acetate, beta-sitosterol 3
O-D-xylopyranoside, menisdaurin and sequoyitol showed weak to moderate activities
with minimum inhibition concentration (MIC) values in the range of 112.5-900
microg/mL against all bacterial strains, while the MIC values for the fungal
strains were in the range of 28.1-450 microg/mL. In the tyrosinase inhibition
assay, a-amyrin acetate was found to be moderately active against tyrosinase with
an inhibition of 62% at 0.1 mg/mL. This activity was lower than that of the
positive control, kojic acid (85%).
PMID- 24354196
TI - Inhibitory effects of stilbene derivatives from Parthenocissus tricuspidata on
adipocyte differentiation and pancreatic lipase.
AB - Obesity, which is characterized by excessive fat accumulation, occurs by fat
absorption by lipase and sequential fat accumulation in adipocytes through
adipocyte differentiation. Thus, inhibition of pancreatic lipase activity and
adipocyte differentiation would be crucial for the prevention and treatment of
obesity. Investigation of anti-obesity compounds from Parthenocissus tricuspidata
stems resulted in the isolation of nineteen compounds including five
acetophenones, five flavonoids and nine stilbene derivatives. Among them, the
stilbene derivatives showed the most potent anti-obesity effects. Stilbene
monomers showed strong inhibitory activity on both adipocyte differentiation and
pancreatic lipase, followed by stilbene dimer and trimer. Flavonoids showed mild
inhibition on adipocyte differentiation, whereas acetophenones showed little
effect in our assay system. Taken together, P. tricuspidata might be a new
candidate for the development of obesity treatment.
PMID- 24354197
TI - HPLC-PDA analysis and anti-inflammatory effects of Mori Cortex Radicis.
AB - Mori Cortex Radicis (MCR, Moraceae) is used traditionally in the treatment
ofjaundice, hematemesis, edema, and pollakisuria in Korea. In this study, the
antiinflammatory effects of MCR extract were investigated using RAW 264.7 cells.
The simultaneous analysis of five components present (neochlorogenic acid,
chlorogenic acid, cryptochlorogenic acid, caffeic acid, and p-coumaric acid) in
the MCR extract was performed using high-performance liquid chromatography (HPLC)
coupled with photodiode array (PDA) detection. We determined the effects of MCR
extract and its components on the production of nitric oxide (NO), prostaglandin
E2 (PGE2), and mRNA expression of cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
MCR extract suppressed the production of NO and PGE2 in RAW 264.7 cells in a dose
dependent manner. None of the five components of the MCR extract had any
influence on the production of NO. However, caffeic acid and p-coumaric acid
inhibited the production of PGE2 and mRNA expression of COX-2 in RAW 264.7 cells.
Our results suggest that MCR extract may offer potential as a therapeutic agent
for the treatment of inflammation. The method we have established will help to
improve the quality control of MCR extracts.
PMID- 24354198
TI - Development of HPLC fingerprint for quality assessment of Bulbus Lilii.
AB - In this study, a simple, sensitive and reliable fingerprint analysis method by
high-performance liquid chromatography coupled with diode array detection (HPLC
DAD) was developed for quality analysis of Bulbus Lilii, which is a famous
traditional Chinese medicine and widely used as a restorative food. Then the
developed method was subsequently applied to analyse 16 samples collected or
purchased from different origins. Twelve common fingerprint peaks, including four
definitely identified peaks, were found in total, and were involved for further
characterisation and quality evaluation of Bulbus Lilii. The chemical quality of
commercial samples collected from different origins varied obviously, indicating
that more attention should be paid to the standardisation of the process of
harvesting, manufacturing and storage of Bulbus Lilii. This is the first time
that a new method has been established to control the quality of Bulbus Lilii
through HPLC-DAD.
PMID- 24354199
TI - Antifungal and antioxidant pyrrole derivative from Piper pedicellatum.
AB - In continuation of our search for efficient pest control natural products from
the flora of the South Eastern Sub-Himalayan biodiversity region, we have
investigated wild edible Piper pedicellatum C. DC (Piperaceae) from Arunachal
Pradesh, India against five important plant pathogenic fungi through an activity
guided method, and a new compound, pedicellamide, was isolated. The structure was
determined on the basis of extensive spectroscopic studies and confirmed by X-ray
crystallography. The compound exhibited antifungal activities against the
phytopathogenic fungal organisms Rhizoctonia solani (MIC 38.4 +/- 1.6 microg/mL),
Fusarium oxysporum (MIC 29.7 +/- 0.8 microg/mL), Aspergillus niger (MIC 48.6 +/-
0.7 microg/mL), Puccinia gramini (MIC 46.8 +/- 1.4 microg/mL) and Curvularia
lunata (MIC 49.1 +/- 0.1 microg/mL). Additionally, the antioxidant potential of
the compound was estimated by DPPH, ABTS and FRAP assay and found to be 2.87 +/-
0.20, 2.19 +/- 0.13 and 3.96 +/- 0.17 VCEAC (microM/g), respectively.
PMID- 24354200
TI - Quorum sensing: a non-conventional target for antibiotic discovery.
AB - Quorum sensing (QS) is known to regulate different functions viz. pathogenesis,
biofilm formation, and host colonization, along with other functions by
regulating bacterial virulence determinants. Therefore, QS is deemed to be an
interesting target to modulate pathogenesis. Also, there have been global reports
of continuous emergence of antibiotic-resistant microbes; hence, an alternative
treatment that compliments antibiotic activity is highly desirable. One such
approach is to look for QS inhibitors, which can quench the virulence phenotypes
exerted by pathogenic bacteria and compliment antibiotic treatment. In the
present study, Pseudomonas aeruginosa strain was used as the model organism which
produces three pigments viz. pyocyanin, pyoverdin and pyorubin. Pyocyanin
synthesis is reported to be QS dependent and is one of the virulence factors of
P. aeruginosa. Hence, we envisage inhibition of pyocyanin pigment would indicate
QS inhibition (QSI). Auto-inducers like N-(3-oxododecanoyl)-L-homoserine lactone
(OdDHL/3-oxo-C12-HSL) and N-butyryl-L- homoserine lactone (BHL/C4-HSL) were used
to enhance the pyocyanin pigment production by the model strain at different
doses and time points. BHL, at 25 microM was found to be a better inducer of
pyocyanin. Tannic acid (TA) was tested to suppress this pigment synthesis and it
was found to be effective when assessed at different time points. About 5.12
mg/mL TA was found to be the optimum concentration at which pyocyanin was
inhibited by 77.3%. Thus, we confirm that TA can be used as a QSI, either in its
purest form or in the crude form found in various plant species, and could be
considered for development to compliment antibiotic therapy.
PMID- 24354201
TI - An alkenylresorcinol derivative from Hakea sericea fruits and their antimicrobial
activity.
AB - Hakea sericea has been introduced to Portugal for ornamental purposes. The
phytochemical composition and the antioxidant, antibacterial, antibiofilm and
cytotoxic properties of this shrub species have been previously reported. The
present work describes the bioassay-guided fractionation of the crude methanolic
extract of H. sericea fruits and the isolation of 9-(3,5-dihydroxy-4
methylphenyl)nona-3(Z)-enoic acid. The structure of this new compound was
established by one- and two-dimensional NMR and IR spectroscopy, and high
resolution mass spectrometry. The antibacterial properties of the new
alkenylresorcinolwere studied by determining its MIC values against several
strains of Gram-positive and Gram-negative bacteria using the resazurin
microtiter assay. The new alkenylresorcinol inhibited the growth of Enterococcus
faecalis, Listeria monocytogenes and Bacillus cereus with MIC values of 0.31,
0.02 and 0.16 mg/mL, respectively. Good MIC values were obtained against
Staphylococcus aureus strains (0.005 - 0.16 mg/mL), including the clinical
isolates (SA 01/10, SA 02/10 and SA 03/10) and MRSA strains.
PMID- 24354202
TI - Glucosinolates in two endemic plants of the Aurinia genus and their
chemotaxonomic significance.
AB - Glucosinolates (GLs) were characterized in the seed and root of Aurinia leucadea
(Guss.) C. Koch and A. sinuata (L.) Griseb., and quantified according to the ISO
9167-1 official method based on the HPLC analysis of desulfo-GLs. Glucoalyssin
(GAL, 1), glucobrassicanapin (GBN, 2) and glucoberteroin (GBE, 3) were the major
GLs identified in A. leucadea and A. sinuata. GC/MS analysis of the volatile
fractions obtained after enzyme hydrolysis showed that they mostly contain
isothiocyanates (ITCs) originating from the parent GLs. On this basis and from
previous reports, C-5 alkyl GLs 1, 2, and 3 can be considered as chemotaxonomic
markers of the Aurinia genus.
PMID- 24354203
TI - Proteinaceous protease inhibitor from Lawsonia inermis: purification,
characterization and antibacterial activity.
AB - A thermo-stable, proteinaceous protease inhibitor (LPI) from Lawsonia inermis is
reported. The LPI was purified from Lawsonia inermis seeds by subsequent ammonium
sulfate precipitation, ion exchange chromatography (DEAE-Cellulose) and gel
permeation chromatography (Sephadex-50). The purified protease inhibitor is
effective against a wide range of proteases viz. papain, trypsin, pepsin and
metallo-protease. The apparent molecular weight of the protease inhibitor is 19
kDa, determined by SDS-PAGE electrophoresis. The protease inhibitor was found to
be stable at 70 degrees C for 30 min. It was also examined for antibacterial
activity against Pseudomonas aeruginosa MTCC 7926 and Staphylococcus aureus NCIM
2079; the IC50 values of the purified LPI were 11.4 microg/mL and 16.6 microg/mL
respectively.
PMID- 24354204
TI - Essential oils composition of croton species from the Amazon.
AB - The essential oils of leaves and twigs from the Euphorbiaceous Croton
draconoides, C. urucurana and Julocroton triqueter were obtained and analyzed by
GC and GC-MS. In total, 101 volatile constituents were identified, comprising an
average of 90% of the oil, mostly made up of mono- and sesquiterpenes. The
monoterpene hydrocarbons varied from 1.2 to 40.2%, the sesquiterpene hydrocarbons
from 34.0 to 49.6% and the oxygenated sesquiterpenes from 11.5 to 51.3%. The main
compounds found in the oil of C. draconoides were beta-pinene (16.9%), alpha
pinene (16.5%), curzerene (12.8%), germacrene D (9.0%), gamma-elemene (4.7%), and
elemol (4.4%). The oil of C. urucurana showed sesquicineole (23.0%), dehydro
sesquicineole (13.8%), beta-caryophyllene (7.9%), beta-bisabolol (5.0%),
germacrene D (4.2%) and beta-elemene (4.1%) as the chief compounds. The oil of J.
triqueter was dominated by beta-caryophyllene (16.3%), beta-phellandrene (10.2%),
spathulenol (5.1%), caryophyllene oxide (5.0%), delta-cadinene (4.3%), (E)
nerolidol (4.3%), and alpha-copaene (4.1%).
PMID- 24354205
TI - Comparative analysis of the essential oil composition of Murraya paniculata and
M. exotica.
AB - Murrayae Folium et Cacumen (MFC) is a traditional Chinese medicine (TCM) derived
from the leaves and twigs of two aromatic species of Rutaceae: Murraya paniculata
(L.) Jack and M. exotica L. It has long been used as a folk medicine in South
China for the treatment of a variety of disorders, particularly for inflammatory
lesions and pains. In the present study, a detailed chemical examination as well
as a comparative analysis of the essential oil composition of M. paniculata and
M. exotica was conducted by gas chromatography-mass spectrometry (GC-MS). A total
of 141 volatile components were identified from the essential oil of these two
plants. Sesquiterpenes were found to be the predominant constituents, accounting
for 92.8% of the oil from M. paniculata and 87.9% of that from M. exotica. A
comparative analysis of the essential oil composition of these two plants
revealed a high level of similarity in their main constituents, such as the co
occurrence of E-caryophyllene, spathulenol and delta-elemene, which gave the
chemical evidence for their equal medicinal application as MFC in TCMs. Moreover,
in combination with literature reports, E-caryophyllene was theoretically deduced
as one of the pharmacologically effective components of MFC that is responsible
for treating inflammatory lesions and for local anaesthesia.
PMID- 24354206
TI - Chemical composition of the essential oil of Erechtites valerianaefolia from
Merida, Venezuela.
AB - The volatile components from the leaves of Erechtites valerianaefolia (Wolf) DC.
were obtained by hydrodistillation and analyzed by GC/MS. A total of 12
compounds, representing 99.8% of the oil, were identified. The dominant compounds
were limonene (56.7%), myrcene (12.7%), trans-beta-farnesene (10.2%) and l
phellandrene (8.7%).
PMID- 24354207
TI - Effect of different drying methods on the essential oils of mint (Mentha
haplocalyx).
AB - The essential oils of fresh, shade-dried, sun-dried, and oven-dried mint of
Mentha haplocalyx Brig., and the shade-dried herbs after one hour of soaking were
analyzed by GC-MS to provide a scientific basis to regulate the drying methods.
Fifty-nine compounds were isolated and identified, including 35 from fresh herbs,
25 from shade-dried herbs, 23 from sun-dried herbs, 17 from oven-dried herbs and
48 from shade-dried mint after one hour of soaking. Eighteen compounds were
common to all five samples, including menthol, menthone, and isomenthone, which
were the main components. Several of these significantly decreased in shade-dried
mint soaked in water. Thus in cleaning and drying processes soaking mint in water
should be avoided as far as possible, in case major components are extracted thus
producing an inferior product that will undermine its curative effect.
PMID- 24354208
TI - Juglans regia and J. nigra, two trees important in traditional medicine: A
comparison of leaf essential oil compositions and biological activities.
AB - The essential oils from the leaves of Juglans regia, collected from Kathmandu,
Nepal, and Juglans nigra from Huntsville, Alabama, USA, were obtained by
hydrodistillation and analyzed by GC-MS. A total of 69 compounds were identified
in the J. regia oil, accounting for 99.0% of the eluting components of the oil
while three different samples of J. nigra were analyzed identifying a total of
99.3%, 99.4% and 99.7% of the oils. The leaf essential oil of J. regia was
dominated by the aromatic compounds eugenol (27.5%) and methyl salicylate
(16.2%), and the sesquiterpenes germacrene D (21.4%) and (E)-beta-farnesene
(8.2%). The essential oils from three different samples of. J. nigra contained
(E)-caryophyllene (17.3%-20.4%) and germacrene D (7.1%-22.5%) with smaller
amounts of juglone (1.0%-8.8%), alpha-hydrojuglone (1.0-9.5%), and delta-cadinene
(3.8%-8.7%). J. regia leaf oil, devoid of juglone, showed allelopathic activity,
while J. nigra leaf oil was less phytotoxic. The presence of eugenol and methyl
salicylate in the leaves of J. regia are consistent with the traditional uses of
this plant to treat toothache, rheumatism, and fungal infections.
PMID- 24354209
TI - Natural compounds against flaviviral infections.
AB - Arthropod borne flaviviral diseases are a major public health concern in the
tropics. However, the majority of cases are associated with Dengue virus (DENV),
Yellow Fever virus (YFV), West Nile virus (WNV) and Chikungunya virus (CHIKV)
infections. Despite their profound clinical and economic impact among large
sections of the population there is a lack of effective treatment against these
diseases. A large number of plants are available in nature, which may act as a
source for lead molecules against various diseases including arthropod borne
flaviviral infections. In this review we discuss various crude extracts as well
as purified compounds from natural sources with promising anti-DENV, YFV, WNV and
CHIKV activity.
PMID- 24354210
TI - Microwave-assisted techniques (MATs); a quick way to extract a fragrance: a
review.
AB - In recent years microwave-assisted techniques (MATs) have been introduced as a
new process design and operation for essential oils extraction, representing a
viable alternative to conventional old-type methods of distillation which are
routinely used for the isolation of essential oils from herbs, flowers and spices
prior to gas chromatographic analysis. The novelty of the technique lies in a
microwave heating source generating a mixture of boiling solvent with the raw
plant material settled above (or drenched inside). Several variations of
distillation techniques are evaluated in terms of substantial energy saving,
rapidity, product yield, cleanliness and product quality. Results confirm the
effectiveness of MATs, which allow extraction of essential oils in shorter
extraction time (up-to 9 times faster), using "greener" procedures and provide a
higher quality essential oil with better sensory and antioxidant properties.
PMID- 24354211
TI - CQC 2013 survey of community mental health services.
PMID- 24354212
TI - Schizophrenia Commission report.
PMID- 24354213
TI - Help yourself.
PMID- 24354214
TI - Gang mentality.
PMID- 24354215
TI - Stressing the possibilities.
PMID- 24354216
TI - Welfare writes: The 'bedroom tax'.
PMID- 24354217
TI - Outside the box: Community treatment orders.
PMID- 24354218
TI - The bigger picture: Children's mental health issues.
PMID- 24354219
TI - A child in mind: Stories, the power of handwriting and its link to emotional self
regulation.
PMID- 24354220
TI - Preparing for the housing needs of people with dementia.
PMID- 24354221
TI - Legal eye: The use of police stations as a 'place of safety' under section 136.
PMID- 24354222
TI - Doctor's orders: Recent developments in synthetic brains and artificial minds.
PMID- 24354223
TI - Network: How a pilot by Mind and NSUN is helping service users to have more
influence over their local mental health services.
PMID- 24354224
TI - Social firms' provision of employment opportunities for people with mental ill
health: a UK survey.
PMID- 24354226
TI - On the record. Looking at ordinary people's tales of living with their mental
illness. Interview by Dan Parton.
PMID- 24354225
TI - Leading the way.
PMID- 24354227
TI - Diabetes as a practice focus.
PMID- 24354228
TI - Cover letter caveats.
PMID- 24354229
TI - Diabetic gastroparesis: an overview of diagnostic and treatment strategies.
PMID- 24354230
TI - Granuloma annulare.
PMID- 24354231
TI - Seeing the connection.
PMID- 24354232
TI - Getting paid for what you do. Tips on nephrology billing for the AP.
PMID- 24354233
TI - Using concordance with dosing techniques to achieve phosphate control.
AB - Concordance, a collaborative planning of treatment regimens fitting patients'
lives, is an under-recognized aspect of sustainable phosphate control. This
article describes one academic dialysis center's patient education intervention,
various dosing methods of sevelamer carbonate powder, improved adherence
patterns, and phosphate control results.
PMID- 24354234
TI - Options in the job market for nephrology fellows.
AB - As one can see, it is not just a matter for you as a nephrology fellow to
identify and determine your best options for a career in nephrology, but it is
also important to be aware of these factors that will affect your ability to
practice medicine and generate satisfactory incomes. Relating to the governmental
issues cited above, it is important that you let your Congressional
representatives and the administration know your concerns. What happens in the
coming months could impact you greatly over the coming years and throughout your
career. You have worked too hard to get to this point not to speak out and get
involved in the process.
PMID- 24354235
TI - Making the PQRS work for you and your practice.
PMID- 24354236
TI - Home dialysis can be a journey to a better quality of life.
PMID- 24354237
TI - [From apixaban to aspirin in the prevention of recurrent venous thromboembolism].
AB - For more than a decade, the only treatments available for the prevention of
recurrent venous thromboembolism, were vitamin K inhibitors, or low molecular
weight heparins (LMWH). Both have been very useful for this purpose; however,
with the inconvenience of required frequent laboratory tests and the risk of
provoking major hemorrhages. LMWH also carry the risk for immune reactions and
the high cost of using it for an extended period of time. With the advent of the
new anticoagulants, there is no need for laboratory tests, but there is no way to
individualize the dose, or to neutralize their effect. They are also very
expensive. Several recent articles have shown that aspirin, as the only treatment
for the prevention of recurrent venous thromboembolism, gave good results in
comparison to placebo. It has also been found that, after hip replacement
surgery, the frequency of thromboembolism was similar in those patients treated
with aspirin and those treated with LMWH. These results could open a new path in
the search for the ideal treatment for the prevention of recurrent venous
thromboembolism.
PMID- 24354238
TI - [blaTEM, blaSHV y blaCTX-M genes in extended-spectrum beta-lactamases producing
enterobacterias isolated from patients with hospital-acquired infections].
AB - The objective of the present investigation was to identify the blaTEM, blaSHV,
and blaCTX-M genes on extended-spectrum beta-lactamases (ESBL) producing
Enterobacteriaceae from clinical isolates, collected between September and
November 2005. In addition to third-generation cephalosporin resistance, the
isolates also showed resistance to chloramphenicol (59.2%), amikacin (37.0%) and
gentamicin (40.7%), and demonstrated sensitivity to imipenem and meropenem. Nine
strains were capable of transferring third-generation cephalosporin resistance,
as well as the production of ESBL. In the clinical isolates, the genes blaSHV,
blaTEM and blaCTX-M were detected, being more prevalent the types blaTEM-1,
blaSHV-1, blaSHV-5 blaSHV-5-2a and blaCTX-M-1; while in the trans-conjugated only
blaTEM-1, blaSHV-5 y blaSHV-5-2awere found. In total, seven types of genes were
identified, five of which were codifying genes for ESBL-type enzymes. This
demonstrates that in the hospital center, resistance to third-generation
cephalosporin is mediated by several enzymes.
PMID- 24354239
TI - [Relationship of food groups intake and C-reactive protein in healthy adults from
Mexicali, Baja California, Mexico].
AB - The high sensitivity C-reactive protein (hs-CRP) is an important biomarker in
inflammatory processes. The objective was to analyze the relationship between the
concentrations of hs-CRP in adults from a northern Mexico region with their
typical food intake patterns. A sample of 72 university professors underwent
clinical and anthropometric assessments and their hs-CRP levels were quantified
with an immunoenzymometric assay. Additionally, they filled out a food intake
frequency questionnaire, from which the servings of different food groups were
obtained with the ESHA software. The average age of participants was 49.75 +/-
10.05 years and the average hs-CRP concentration was 1.66 (0.97, 3.52) mg/L. The
value of the association between fruit consumption and hs-CRP level was
protective, according to the logistic regression analysis, being the Odds Ratio
(OR) 0.23 (95% CI: 0.05, 1.03); while for vegetables the OR was 0.66 (95% CI:
0.12, 3.68). Furthermore, high protein content foods, dairy products, oils and
fats were associated with elevated levels of hs-CRP. In conclusion, in our study,
the intake of some food groups like fruits and vegetables, and to a lesser extent
cereals, were associated with low values of hs-PCR.
PMID- 24354240
TI - Production and evaluation of chicken antibodies against a synthetic peptide from
glial growth factor.
AB - Neuregulins (NRG) are proteins that belong to the family of epidermal growth
factors. It is well established that these factors are essential for the
development and maintenance of the nervous system. Due to the difficulty of
purifying enough quantities of these factors and the lack of specificity from
commercially available antibodies, the aim of this work was to produce antibodies
against a synthetic peptide capable to detect and identify neuregulin GGFbeta
isoforms. To accomplish this goal, polyclonal antibodies were raised in hens
against a synthetic peptide designed from the GGFbeta1 extracellular sequence.
The sequence analysis was made using different epitope-predicting programs. Our
results showed that the peptide sequence selected was immunogenic because it was
capable of inducing a specific type B immune response in the experimental animal
model. These antibodies were also capable of recognizing a recombinant GGF
protein and GGF isoforms present in different samples. Our results suggest that
the development of immunoglobulin Y (IgY) using synthetic peptides represents, a
valuable tool for neuroscience research.
PMID- 24354241
TI - [Description of an acidic peptidase, insensitive to classical inhibitors, in
protein extracts of Trypanosoma cruzi, from a rural area of Venezuela, where
Chagas disease is endemic].
AB - Through two peptidase assay methods, one in liquid-phase and another, in gel
phase (gel zymography), an acid peptidase was detected in protein crude extracts
of epimastigotes of Trypanosoma cruzi, from a rural area of Venezuela where
Chagas disease is endemic. The peptidase shows activity at a pH range between 2.0
and 2.9. Under the experimental conditions described, the acid peptidase was
insensitive to usual concentrations of peptidase inhibitors of the types: serine,
cysteine, aspartic and metallopeptidases. Nevertheless, like porcine pepsin at pH
2.9, the peptidase was inhibited in the presence of 5mM DTT.
PMID- 24354242
TI - [Increased expression of the c-Met receptor mRNA in gastric cancer].
AB - Gastric cancer is one of the most common malignancies in the world. In the last
decades, the attention has been focused in possible alterations of genetic
factors that include proto-oncogene activation and/or the tumor suppressor gene
inactivation. The product of the proto-oncogene c-MET and its ligand, hepatocyte
growth factor (HGF), have been implicated in cell proliferation and migration in
gastric cancer. In this study we analyzed at the molecular level, the
amplification of c-Met receptor mRNA from gastric tumor tissue of patients who
underwent gastrectomy, using the acid guanidinium-thiocyanate-phenol-chloroform
method and the semiquantitative Reverse Transcriptase-Polymerase Chain Reaction
(RT-PCR) method. It was found that high levels of c-Met receptor mRNA in tumor
samples from patients are associated with greater depth of invasion in the
gastric wall (r = 0.762, p < 0.01), increase in metastases to lymph nodes (r =
0.766, p < 0.01), high frequency of poorly differentiated or undifferentiated
tumors (r = 0.912, p < 0.001), increase in the gastric cancer staging (r = 0.838,
p < 0.001), and the overexpression, by the immunohistochemistry method (IHC) of
the labeled streptavidin-biotin, of the c-Met receptor at the protein level (r =
0.858, p < 0.001). The amplification of mRNA and/or protein level overexpression
of the c-Met receptor could be used as prognostic factors in gastric cancer.
PMID- 24354244
TI - [Factors involved in host-pathogen interaction for the risk of Hodgkin lymphoma
induced by Epstein Barr virus].
AB - Hodgkin lymphoma (HL) is a neoplasm characterized by malignant cells called Reed
Sternberg and Hodgkin's cells in the lymphatic system. Such cells comprise 1% of
the tumor while the remainder is made up of lymphocytes, histiocytes, eosinophils
and plasma non-neoplastic cells. The annual global incidence of HL is 3
10/100,000 inhabitants and is most commonly found in young adults. The mechanism
by which cell transformation is accomplished is not entirely clear; however, some
evidences suggest that oncogenic viruses like the Epstein Barr virus (EBV) may
have a high impact on the pathogenesis of lymphoproliferation. Genetic and
environmental factors could be involved, since it has been found a high incidence
of HL among members of the same family. In Mexico, there have been studies to
determine the prevalence of EBV in patients with HL and found the presence of
this virus in up to 64.2% of the cases. EBV has been detected in the Reed
Sternberg cells and Hodgkin cells in 50% of cases of classical HL. There is not a
satisfactory explanation for this, but it has been proposed that geographic and
immunological variabilities play a role in the positivity of EBV in HL. However,
despite recent advances in the field, there is insufficient evidence to show a
clear association between host factors, environment and pathogens, and the risk
of lymphoproliferation leading to the development of HL. This review aims to give
an overview about the risk factors that influence the interaction of host,
pathogens and environment in the etiology of HL.
PMID- 24354243
TI - [Frequency of gastrointestinal signs and symptoms of dengue. Analysis of a cohort
of 1484 patients].
AB - Dengue is characterized by fever, headache, arthralgia and myalgia. The presence
of gastrointestinal signs and symptoms (GISS) is considered a sign of alarm in
dengue; however, little information exists regarding the occurrence of these
events. The aim of this study was to determine the frequency of gastrointestinal
signs and symptoms in a cohort of patients with dengue. A total of 1484 medical
records of patients with confirmed dengue were reviewed and classified as: dengue
without warning signs (DNWS) (n = 700), dengue with warning signs (DWWS) (n =
700) and severe dengue (SD) (n = 84). Of the studied records, 65.71% of patients
with DNWS, 92.59% with DWWS and 100% of patients with SD had GISS. In patients
with DNWS, nausea / vomiting were the most common symptoms in 319/700 cases
(45.57%), followed by abdominal pain in 142/700 (20.29%) and diarrhea in 125/700
(17.86%). There were no cases with melena, hepatomegaly or hematemesis. While in
DWWS nausea/vomiting were present in 529/700 (75.57%), abdominal pain in 439/700
(62.71%) and diarrhea in 198/700 (28.28%),(p <0.0001). Melena, hematemesis and
hepatomegaly ranged from 0.57% to 1.86% of cases. In SD, nausea/vomiting were
registered in 100% of the cases, abdominal pain in 82/84 (97.62%), diarrhea in
65/84 (77.38%), melena in 32/84 (38.10%), hepatomegaly in 28/84 (33.33%) and
hematemesis in 26/84 (30.95%). It was evident the high frequency of GISS in cases
of DWWS and SD, in contrast to DNWS, in which the frequency of GISS was
significantly lower. This suggests a relationship of GISS with the severity of
dengue, and their presence should be considered by the decision-making health
team for appropriate patient management.
PMID- 24354245
TI - [Autophagy and immune response].
AB - Autophagy is a complex process in which cell homeostasis of proteins, organelles,
exocitic and endocitic vacuoles are controlled. There is a direct link between
autophagy and cell death with antigen processing, generation of inflammatory
response and immune response. In different diseases, deficiencies in autophagy
have been reported. It has been proposed that in early stages of cancer,
autophagy is capable of inducing cell death; however, in agresive tumors and
metastasis, the process is responsible for pharmacologic resistance and tumor
survival. More research has to be done in order to allow us to understand the
process and generate therapeutic options in different pathologies important for
the human being.
PMID- 24354246
TI - [The intestinal parasitic diseases as a global health problem].
PMID- 24354247
TI - [The White Paper of the European pulmonology].
PMID- 24354248
TI - [Lung and pregnancy].
AB - During pregnancy several adaptations develop in response to the enhanced maternal
and fetal metabolic needs. This review summarizes the major cardiorespiratory
modifications of pregnancy as well as their consequences in chronic respiratory
diseases such as restrictive ventilatory defects (post-tuberculosis
pneumonectomy, kyphoscoliosis, neuromuscular disorders), asthma, cystic fibrosis,
and pulmonary hypertension. It is important to recognize early the
cardiorespiratory situations for which pregnancy is contraindicated or associated
with a high risk of respiratory complications. Clinical management by an expert
and often pluridisciplinary team is recommended.
PMID- 24354249
TI - [Positional obstructive sleep apnea syndrome].
AB - Obstructive sleep apnea (OSA) tends to worsen on the supine posture due to the
effect of gravity on tongue position. In some cases, OSA is present exclusively
on the supine posture (exclusive postural OSA). These patients may benefit from
positional therapy (PT), which aim is to prevent sleep in the supine posture
using different types of devices. Before opting for this therapeutic option, a
sleep study with PT should be perform in order to confirm its efficacy and assess
the patients' tolerance. Because the efficacy of PT is inferior to continuous
positive airway pressure (CPAP), the latter treatment remains the first line of
therapy. Also, the discomfort of the existing devices appears to limit the long
term use of PT. Further studies assessing the long term effects of PT on
metabolic and neurocognitive outcomes are needed.
PMID- 24354250
TI - [Bronchiectasis: diagnostic workup].
AB - Bronchiectasis is a condition defined by permanent dilation of the bronchi,
either idiopathic or associated with other disease states. Diagnostic workup for
bronchiectasis is essential in determining management and treatment. For diffuse
bronchiectasis, we propose a workup plan that includes testing for humoral
immunodeficiency by measuring serum IgG and anti-pneumococcal antibodies, looking
for primary ciliary dyskinesia by exhaled nasal NO and cytologic brush biopsy of
the nasal mucosa, looking for cystic fibrosis by chloride sweat testing and
genotyping, evaluation for allergic bronchopulmonary aspergillosis, and testing
for alpha-1-antitrypsin deficiency. Workup studies should be guided by the
patient's history and clinical context.
PMID- 24354251
TI - [Cryptogenic organizing pneumonia].
AB - Cryptogenic organizing pneumonia (COP) is a distinct clinico-pathologic entity
described for the first time by Davison in 1983 and 2 years later by Epler under
the name of idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP). It
most often presents with the clinical and radiological features of an infectious
pneumonia which fails to respond to antibiotic therapy. In this article, we will
review the clinical and radiographic features, diagnostic assessment, and the
treatment of COP.
PMID- 24354252
TI - [The role of surgery in early stage small cell lung cancer: should it be re
evaluated?].
AB - Two historical randomized controlled trials have demonstrated that chemo
radiotherapy offers the best survival advantage over surgery in small cell lung
carcinoma (SCLC) and led to abandon surgery for the treatment of SCLC. Yet,
widespread use of CT scanning increases the detection of early and very early
stage SCLC. Therefore, the traditional 2 stages classification scheme--namely
limited and extensive stage disease--is no longer sufficient for such early stage
disease and must be completed by the TNM classification. Although randomized
controlled trials are lacking, retrospective case series and large population
databases suggest a beneficial role of surgery for the earliest SCLC stages. It
is thus currently recommended to consider surgery in the multimodal treatment of
stage I SCLC.
PMID- 24354253
TI - [Granulomatous lymphocytic interstitial lung disease in common variable
immunodeficiency].
AB - Common variable immunodeficiency (CVID) is the most frequent primary immune
deficiency. Recurrent infections are classical consequences of CVID, but their
impact has been largely reduced by immunoglobulin replacement. CVID is also
associated with various inflammatory and autoimmune manifestations resulting from
abnormal cellular immunity. The lungs are especially affected by a recently
described entity called granulomatous lymphocytic interstitial lung disease
(GLILD). GLILD currently constitutes an important cause of morbidity and
mortality in these patients. It is distinct from bronchiectasis secondary to
recurrent infections, and presents similarities but also striking differences
with sarcoidosis.
PMID- 24354254
TI - [Renal masses and indication to nephrectomy: preoperative assessment and clinical
presentation of five cases].
AB - In Switzerland, renal cancer represents 2% of adult neoplasia and its incidence
is 8,2 cases per 100000 people. Small renal masses (< 4 cm) are mostly found
incidentally during ultrasound or CT-scan evaluations. Differentiation between
benign lesions (20% of renal masses < 4 cm), cancer and pseudotumors may be
difficult. CT-scan plays a central role in the preoperative assessment, but the
use of renal biopsy seems to have a growing importance in this assessment. This
article summarizes the different diagnostic approaches in the preoperative
assessment and describes five cases of nephrectomy for renal masses incidentally
discovered.
PMID- 24354255
TI - [Helping medical students to approach death].
AB - A project recently launched by the Faculty of biology and medicine of Lausanne
introduces the approach of facing death during both the dissection and the course
of clinical activities. Existential questions relating to mortality are bound to
arise sooner or later during the course of the study. For the sake of humanized
clinical practice, these questions must be confronted. In response to a request
by a student association, an accompanying curriculum with active student's
contribution through encounters with death in anatomy and clinical situations was
created in Lausanne. Students will benefit from this new program throughout their
curriculum. This program is the first of its kind in Switzerland.
PMID- 24354257
TI - [Advance directives].
PMID- 24354256
TI - [Knee: four hundred and thirty years to confirm the existence of a ligament].
PMID- 24354258
TI - [The great psychiatrists have no statue or street name].
PMID- 24354259
TI - [Desire of the French government: penalize the clients of prostitute(s)].
PMID- 24354260
TI - [The importance of myths].
PMID- 24354261
TI - [Current trend of glaucoma medication with various eye drops].
PMID- 24354262
TI - [Comparison of visual acuity and central macular thickness after vitrectomy for
diffuse diabetic macular edema with or without preoperative treatments].
AB - PURPOSE: To compare the surgical outcomes during pars plana vitrectomy (PPV) for
diffuse diabetic macular edema (DME) with pretreatment to those without
pretreatment. METHODS: The medical charts of 43 eyes of 46 patients who underwent
PPV for DME were reviewed. The previously treated (Prev. Tx) group included 19
eyes of 20 patients who were pretreated with intravitreal bevacizumab, sub-Tenon
injection of triamcinolone acetonide, and/or subthreshold micropulse diode laser
photocoagulation before the PPV. The treatment naive (Tx.Naive) group included 24
eyes of 26 patients who underwent PPV alone. The central macular thickness (CMT)
and best-corrected visual acuity (BCVA) were measured before treatment and 1, 3,
and 6 months after. RESULTS: In both groups, BCVA at 3 and 6 months and CMT at 1
month or later were significantly better than preoperative visual acuity. CMT at
1 month or later significantly decreased from the preoperative value (p<0.05).
The differences in the BCVA and CMT between the Prev. Tx and Tx.Naive group were
not significant. CONCLUSIONS: PPV either with or without preoperative treatments
can significantly improve the BCVA and reduce the CMT in patients with diffuse
DME.
PMID- 24354263
TI - [Clinical efficacy of travoprost-timolol fixed combination on ocular hypotensive
agents and ocular surface agents in Japanese glaucoma patients].
AB - PURPOSE: To investigate the clinical effects of travoprost-timolol fixed
combination on ocular hypotensive agents, ocular surface agents and adherence in
Japanese glaucoma patients. METHODS: 28 Japanese glaucoma patients, who had used
topical prostaglandin F2alpha analogue (28 eyes; PG group), were assigned to
treatment with travoprost-timolol fixed combination. Reduction of intraocular
pressure (IOP), grades of conjuctival follicle, conjuctival injection and
keratoepitheliopathy, as well as interviews for topical administration, were
evaluated. 38 patients, who switched from the topical prostaglandin F2alpha
analogue and a beta-blocker to travoprost-timolol fixed combination (38eyes:
PG+BB group) were also evaluated in the same manner. RESULTS: While IOP was
significantly reduced in the PG group, IOP was not changed in the PG+BB group.
Both groups showed no significant changes in scores for conjuctival follicle,
keratoepitheliopathy, or interview. CONCLUSION: These results suggest that
travoprost-timolol fixed combination reduces IOP and produces low toxicity on the
ocular surface.
PMID- 24354264
TI - [Clinical findings and macular lesions in basal laminar drusen].
AB - PURPOSE: To investigate the clinical characteristics and accompanying macular
lesions in Japanese patients with basal laminar drusen (BLD). DESIGN:
Retrospective cross-sectional study. PATIENTS AND METHODS: Fifty four eyes of 27
Japanese patients with BLD were examined for the clinical characteristics of BLD
and accompanying macular lesions using retro-mode imaging (Scanning Laser
Ophthalmoscope F-10, Nidek) in addition to current methods such as fluorescein
angiography (FA), indocyanine green angiography (IA), fundus autofluorescence
(FAF) and spectral domain optical coherence tomography (SD-OCT). RESULTS: 1)BLD
was more clearly identified using retro-mode imaging than any of the other
current imaging methods, and was divided into two types: a crater type
(relatively sparsely distributed BLD with many soft drusens) and a mesh type
(uniformly distributed BLD). 2) BLD in both eyes was more common in female
patients, and had the same type, distribution and similar macular lesions in both
eyes. 3) Among the macular lesions, we observed macular atrophy, retinal
angiomatous proliferation and vitelliform detachment in many patients, in
contrast to few cases of choroidal neovascularization and no polypoidal choroidal
vasculopathy. CONCLUSIONS: BLD may be regarded as a disease that is different
from age-related macular degeneration (AMD).
PMID- 24354265
TI - [Night visual function of glaucoma patients with good photopic vision].
AB - PURPOSE: To measure night visual function of glaucoma patients with good photopic
vision. SUBJECTS AND METHODS: Patients aged 30-59 years who were diagnosed with
glaucoma in the outpatient clinic of Nara Medical University, and showed a
corrected visual acuity of > or = 1.0 in both eyes. The patients were classified
using static threshold perimetry with a Humphrey field analyzer into two groups,
with a mean deviation of -6 dB or better (early-stage glaucoma group) or a mean
deviation worse than -6dB (intermediate/late-stage glaucoma group), and night
visual function was measured. In addition, the patients were compared with normal
controls without eye disease other than refractive error. RESULTS: The early
stage glaucoma group included 26 patients, and the intermediate/late-stage
glaucoma group included 22 patients. There were 23 controls. Night visual
function differed among the 3 groups. With the progression of visual field
defects, the night visual function decreased. CONCLUSION: These results suggest
that night visual function can be used as a new parameter for the evaluation of
visual function in glaucoma patients.
PMID- 24354266
TI - A nanoparticle-based ratiometric and self-calibrated fluorescent thermometer for
single living cells.
AB - The homeostasis of body temperature and energy balance is one of the major
principles in biology. Nanoscale thermometry of aqueous solutions is a
challenging but crucial technique to understand the molecular basis of this
essential process. Here, we developed a ratiometric nanothermometer (RNT) for
intracellular temperature measurement in real time. Both the thermosensitive
fluorophore, beta-diketonate chelate europium(III) thenoyltrifluoroacetonate, and
the thermoinsensitive fluorophore, rhodamine 101, which was used as a self
reference, are embedded in a polymeric particle that protects the fluorophores
from intracellular conditions. The ratiometric measurement of single RNT spots is
independent of the displacement of the RNT along the z-axis. The temperature is
therefore determined at the location of each RNT under an optical microscope
regardless of the dynamic movement of living cells. As a demonstration of the
spot-by-spot intracellular thermometry, we successfully followed the temperature
change in individual RNT spots in a single cell together with the Ca(2+) burst
induced by the Ca(2+) ionophore ionomycin. The temperature increases differently
among different spots, implying heterogeneous heat production in the cell. We
then show that, in some spots, the temperature gradually decreases, while in
others it remains high. The average temperature elevation within a cell is
positively correlated to the increase in Ca(2+), suggesting that the activity
and/or number of heat sources are dependent on the Ca(2+) concentration.
PMID- 24354267
TI - Agarose hydrogel biomimetic mineralization model for the regeneration of enamel
prismlike tissue.
AB - Laboratory studies have demonstrated that enamel-like mineralized tissue can be
regenerated and used to repair enamel loss. This has implications for the
management of noncarious tooth loss resulting from dental erosion, attrition, and
abrasion. In this study, we designed a hydrogel biomimetic mineralization model
for the regeneration of enamel-like mineralized tissue with a prismatic
structure. The mineralized tissue, which was generated by the model on an etched
enamel surface in the presence of 500 ppm fluoride, was analyzed with scanning
electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy,
and the nanoindentation hardness test. The generated tissue had enamel prismlike
layers containing well-defined hexagonal hydroxyapatite crystals. The modulus of
elasticity and the nanohardness of the regenerated enamel prismlike tissue were
similar to those of natural enamel. Thus, the regeneration of enamel using this
hydrogel biomimetic mineralization model is a promising approach for the
management of enamel loss.
PMID- 24354268
TI - Localized, stepwise template growth of functional nanowires from an amino acid
supported framework in a microfluidic chip.
AB - A spatially controlled synthesis of nanowire bundles of the functional
crystalline coordination polymer (CP) Ag(I)TCNQ (tetracyanoquinodimethane) from
previously fabricated and trapped monovalent silver CP (Ag(I)Cys (cysteine))
using a room-temperature microfluidic-assisted templated growth method is
demonstrated. The incorporation of microengineered pneumatic clamps in a two
layer polydimethylsiloxane-based (PDMS) microfluidic platform was used. Apart
from guiding the formation of the Ag(I)Cys coordination polymer, this
microfluidic approach enables a local trapping of the in situ synthesized
structures with a simple pneumatic clamp actuation. This method not only enables
continuous and multiple chemical events to be conducted upon the trapped
structures, but the excellent fluid handling ensures a precise chemical
activation of the amino acid-supported framework in a position controlled by
interface and clamp location that leads to a site-specific growth of Ag(I)TCNQ
nanowire bundles. The synthesis is conducted stepwise starting with Ag(I)Cys CPs,
going through silver metal, and back to a functional CP (Ag(I)TCNQ); that is, a
novel microfluidic controlled ligand exchange (CP -> NP -> CP) is presented.
Additionally, the pneumatic clamps can be employed further to integrate the
conductive Ag(I)TCNQ nanowire bundles onto electrode arrays located on a surface,
hence facilitating the construction of the final functional interfaced systems
from solution specifically with no need for postassembly manipulation. This
localized self-supported growth of functional matter from an amino acid-based CP
shows how sequential localized chemistry in a fluid cell can be used to integrate
molecular systems onto device platforms using a chip incorporating
microengineered pneumatic tools. The control of clamp pressure and in parallel
the variation of relative flow rates of source solutions permit deposition of
materials at different locations on a chip that could be useful for device array
preparation. The in situ reaction and washing procedures make this approach a
powerful one for the fabrication of multicomponent complex nanomaterials using a
soft bottom-up approach.
PMID- 24354270
TI - Controlled photocatalytic growth of Ag nanocrystals on brookite and rutile and
their SERS performance.
AB - Ag nanocrystals (NCs) were photocatalytically grown on the surfaces of brookite
and rutile nanocrystals, respectively, and their surface-enhanced Raman
scattering (SERS) performance was evaluated. The resultant Ag NCs exhibit
different morphologies owing to the different photocatalytic capabilities of the
two types of TiO2 under otherwise identical synthetic conditions. The effects of
AgNO3 concentration, UV irradiation time, and UV light power on the morphology
evolution and growth kinetics of the Ag NCs were systematically investigated.
Moreover, PVP was found to serve as both a reductant and a capping agent in the
photocatalytic reaction systems, and its presence allows morphological control of
the Ag NCs. A proper amount of PVP was confirmed to favor Ag nanoplates of larger
sizes and to produce SERS substrates of substantially better performance.
PMID- 24354269
TI - Conjugation with receptor-targeted histidine-rich peptides enhances the
pharmacological effectiveness of antisense oligonucleotides.
AB - Ineffective delivery to intracellular sites of action is one of the key
limitations to the use of antisense and siRNA oligonucleotides as therapeutic
agents. Here, we describe molecular scale antisense oligonucleotide conjugates
that bind selectively to a cell surface receptor, are internalized, and then
partially escape from nonproductive endosomal locations to reach their sites of
action in the nucleus. Peptides that include bombesin sequences for receptor
targeting and a run of histidine residues for endosomal disruption were
covalently linked to a splice switching antisense oligonucleotide. The conjugates
were tested for their ability to correct splicing and up-regulate expression of a
luciferase reporter in prostate cancer cells that express the bombesin receptor.
We found that trivalent conjugates that included both the targeting sequence and
several histidine residues were substantially more effective than conjugates
containing only the bombesin or histidine moieties. This demonstrates the
potential of creating molecular scale oligonucleotide conjugates with both
targeting and endosome escape capabilities.
PMID- 24354271
TI - Template-activated strategy toward one-step coating silica colloidal microspheres
with sliver.
AB - Template-activated strategy was developed to coat silica (SiO2) colloidal
microspheres with silver in one step, based on one-pot hydrothermal treatment of
silver nitrate, PVP (poly(vinyl pyrrolidone)), and SiO2 colloidal microspheres in
ammonia solution. In our reaction system, the surface of SiO2 colloidal
microspheres was continually activated with negative-charged SiO(-) groups in
ammonia solution, which accumulated [Ag(NH3)2](+) or Ag(+) ions around the SiO2
colloidal microspheres through electrostatic attraction; thereafter these ions
could be reduced into Ag nanoparticles in situ by the weak reducer PVP in the
solution, and then acted as seeds for the subsequent complete silver coating with
the reaction proceeding. Therefore, the traditional three steps for complete
silver coating, including prior surface modification, seeding, and subsequent
growing, were effectively integrated into one step. The experimental results
exhibited that perfect SiO2/Ag core/shell composite microspheres were
successfully synthesized through optimizing the reaction parameters like the
solvent ingredient, reducer, and the reaction temperature. Additionally, these
obtained uniform composite microspheres were further used as SERS substrate by
using R6G and thiram as probe molecules, and showed excellent trace detection of
these organic chemicals in solution.
PMID- 24354272
TI - Cysteine is the general base that serves in catalysis by isocitrate lyase and in
mechanism-based inhibition by 3-nitropropionate.
AB - Isocitrate lyase (ICL) catalyzes the reversible cleavage of isocitrate into
succinate and glyoxylate. It is the first committed step in the glyoxylate cycle
used by some organisms, including Mycobacterium tuberculosis, where it has been
shown to be essential for cell survival during chronic infection. The pH-rate and
pD-rate profiles measured in the direction of isocitrate synthesis revealed
solvent kinetic isotope effects (KIEs) of 1.7 +/- 0.4 for (D2O)V and 0.56 +/-
0.07 for (D2O)(V/Ksuccinate). Whereas the (D2O)V is consistent with partially
rate-limiting proton transfer during formation of the hydroxyl group of
isocitrate, the large inverse (D2O)(V/Ksuccinate) indicates that substantially
different kinetic parameters exist when the enzyme is saturated with succinate.
Inhibition by 3-nitropropionate (3-NP), a succinate analogue, was found to
proceed through an unusual double slow-onset process featuring formation of a
complex with a Ki of 3.3 +/- 0.2 MUM during the first minute, followed by
formation of a final complex with a Ki* of 44 +/- 10 nM over the course of
several minutes to hours. Stopped-flow measurements during the first minute
revealed an apparent solvent KIE of 0.40 +/- 0.03 for association and unity for
dissociation. In contrast, itaconate, a succinate analogue lacking an acidic
alpha-proton, did not display slow-binding behavior and yielded a (D2O)Ki of 1.0
+/- 0.2. These results support a common mechanism for catalysis with succinate
and inhibition by 3-NP featuring (1) an unfavorable prebinding isomerization of
the active site Cys191-His193 pair to the thiolate-imidazolium form, a process
that is favored in D2O, and (2) the transfer of a proton from succinate or 3-NP
to Cys191. These findings also indicate that propionate-3-nitronate, which is the
conjugate base of 3-NP and the "true inhibitor" of ICL, does not bind directly
and must be generated enzymatically.
PMID- 24354273
TI - Hierarchically self-organized monolithic nanoporous membrane for excellent virus
enrichment.
AB - Enrichment of viruses is essential for making high dose viral stocks for vaccines
and virus-related research. Since the widely used ultracentrifugation for
concentrating viral stock requires ultra-high speed rotation, it easily destroys
the activity of some viruses, for instance, hepatitis c virus (HCV), which has a
fragile structure and low virus titer. We introduce a novel method to concentrate
HCV virus in stock by using a hierarchically self-organized monolithic nanoporous
membrane made by stepwise anodization. The pores at the top part of the membrane
have very regular sizes that are suitable for the perfect filtration of the virus
particles in the stock. On the other hand, the remaining part has large pores
that maintain high flux and mechanical strength of the membrane under the high
pressure (up to 10 bar). The enrichment efficiency of HCV in crude stocks by
using the membrane became over 91%, which is four times higher than that (~22%)
obtained by conventionally used centrifugation. A very high efficiency results
from the perfect filtration and no damage to the virion particles during the
enrichment process, whereas significant damage to the HCV occurs during
centrifugation. The hierarchically self-organized monolithic nanoporous membrane
could be effectively employed for concentrating various fragile viruses in
stocks, for instance, rabies virus and human immunodeficiency virus in addition
to HCV virus.
PMID- 24354274
TI - Effect of poly(ethylene oxide) homopolymer and two different poly(ethylene oxide
b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers on
morphological, optical, and mechanical properties of nanostructured unsaturated
polyester.
AB - Novel nanostructured unsaturated polyester resin-based thermosets, modified with
poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO), and two poly(ethylene
oxide-b-propylene oxide-b-ethylene oxide) block copolymers (BCP), were developed
and analyzed. The effects of molecular weights, blocks ratio, and curing
temperatures on the final morphological, optical, and mechanical properties were
reported. The block influence on the BCP miscibility was studied through uncured
and cured mixtures of unsaturated polyester (UP) resins with PEO and PPO
homopolymers having molecular weights similar to molecular weights of the blocks
of BCP. The final morphology of the nanostructured thermosetting systems,
containing BCP or homopolymers, was investigated, and multiple mechanisms of
nanostructuration were listed and explained. By considering the miscibility of
each block before and after curing, it was determined that the formation of the
nanostructured matrices followed a self-assembly mechanism or a polymerization
induced phase separation mechanism. The miscibility between PEO or PPO blocks
with one of two phases of UP matrix was highlighted due to its importance in the
final thermoset properties. Relationships between the final morphology and
thermoset optical and mechanical properties were examined. The mechanisms and
physics behind the morphologies lead toward the design of highly transparent,
nanostructured, and toughened thermosetting UP systems.
PMID- 24354276
TI - Fluorescence light-up probe for parallel G-quadruplexes.
AB - Putative G-quadruplex-forming sequences (PQS) are highly prevalent in human
genome; however, the structures and functions of most PQSs in genome are poorly
understood. Therefore, selective recognition of certain types of G-quadruplexes
(G4s) is important for the study of G4s. A new light up fluorescent probe, BPBC
composed of benzimidazole and carbazole moieties was designed and synthesized.
BPBC possesses a crescent-shaped pi-conjugated planar core that is slightly
larger than the dimension of the G-quartet plane in G4s. This structure endows
BPBC with excellent selectivity to parallel G4s. BPBC exhibits almost no
fluorescence in the aqueous buffer condition, its fluorescence increases
approximately 330-1800-fold in the presence of parallel G4s but only about 30
fold in the presence of single/double-stranded (ss/ds) DNA and 30-110-fold in the
presence of antiparallel G4s. Binding studies indicate that the highly selective
fluorescent response of BPBC arises from end-stack binding model to G-quartet.
PMID- 24354275
TI - Chlamydia trachomatis CT771 (nudH) is an asymmetric Ap4A hydrolase.
AB - Asymmetric diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap4A) hydrolases are
members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A
into ATP and AMP while facilitating homeostasis. The obligate intracellular
mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein,
CT771. As pathogens that rely on a host for replication and dissemination
typically have one or zero Nudix family proteins, this suggests that CT771 could
be critical for chlamydial biology and pathogenesis. We identified orthologues to
CT771 within environmental Chlamydiales that share active site residues
suggesting a common function. Crystal structures of both apo- and ligand-bound
CT771 were determined to 2.6 A and 1.9 A resolution, respectively. The structure
of CT771 shows a alphabetaalpha-sandwich motif with many conserved elements
lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771
structure mirror those observed in the ligand-bound structure of the Ap4A
hydrolase from Caenorhabditis elegans. These structures represent only the second
Ap4A hydrolase enzyme member determined from eubacteria and suggest that
mammalian and bacterial Ap4A hydrolases might be more similar than previously
thought. The aforementioned structural similarities, in tandem with molecular
docking, guided the enzymatic characterization of CT771. Together, these studies
provide the molecular details for substrate binding and specificity, supporting
the analysis that CT771 is an Ap4A hydrolase (nudH).
PMID- 24354277
TI - In situ modification of the silica backbone leading to highly porous monolithic
hybrid organic-inorganic materials via ambient pressure drying.
AB - We report the synthesis of monolithic porous hybrid organic-inorganic materials
based on tetraethoxysilane (TEOS) and a bifunctional precursor synthesized from 3
aminopropyltriethoxysilane (APTES) and 3-glycidoxypropyltrimethoxysilane (GLYMO)
via base catalysis. To compensate for the slower hydrolysis and condensation rate
of the organically modified silane in basic media, it was prehydrolysed prior to
adding it to the silane solution. This process leads to a lower shrinkage and
stable monoliths with densities as low as 200 kg/m(3). Analysis of the samples
supports the assumption that the porous monolithic materials derived via ambient
pressure drying of the gels consist of a network of homogeneous hybrid primary
particles. These particles are larger than their inorganic counterparts in
classical silica gels and therefore the capillary forces while drying the gels at
ambient pressure are reduced. This leads to less shrinkage and thus lower
densities of the materials derived via ambient pressure drying. An inorganic
xerogel with the same low density can be achieved by a subsequent oxidation step
that decomposes the organic moieties.
PMID- 24354278
TI - Mechanism of dimerization of a recombinant mature vascular endothelial growth
factor C.
AB - The vascular endothelial growth factors (VEGFs) and their tyrosine kinase
receptors play a pivotal role in angiogenesis and lymphangiogenesis during
development and in pathologies such as tumor growth. The VEGFs function as
disulfide-linked antiparallel homodimers. The lymphangiogenic factors, VEGF-C and
VEGF-D, exist as monomers and dimers, and dimerization is regulated by a unique
unpaired cysteine. In this study, we have characterized the redox state of this
unpaired cysteine in a recombinant mature monomeric and dimeric VEGF-C by mass
spectrometry. Our findings indicate that the unpaired cysteine regulates
dimerization via thiol-disulfide exchange involving the interdimer disulfide
bond.
PMID- 24354279
TI - From GaN to ZnGa(2)O(4) through a low-temperature process: nanotube and
heterostructure arrays.
AB - We demonstrate a method to synthesize GaN-ZnGa2O4 core-shell nanowire and ZnGa2O4
nanotube arrays by a low-temperature hydrothermal process using GaN nanowires as
templates. Transmission electron microscopy and X-ray photoelectron spectroscopy
results show that a ZnGa2O4 shell forms on the surface of GaN nanowires and that
the shell thickness is controlled by the time of the hydrothermal process and
thus the concentration of Zn ions in the solution. Furthermore, ZnGa2O4 nanotube
arrays were obtained by depleting the GaN core from GaN-ZnGa2O4 core-shell
nanowire arrays during the reaction and subsequent etching with HCl. The GaN
ZnGa2O4 core-shell nanowires exhibit photoluminescence peaks centered at 2.60 and
2.90 eV attributed to the ZnGa2O4 shell, as well as peaks centered at 3.35 and
3.50 eV corresponding to the GaN core. We also demonstrate the synthesis of GaN
ZnGa2O4 heterojunction nanowires by a selective formation process as a simple
route toward development of heterojunction nanodevices for optoelectronic
applications.
PMID- 24354280
TI - Passivated aluminum nanohole arrays for label-free biosensing applications.
AB - We report the fabrication and performance of a surface plasmon resonance aluminum
nanohole array refractometric biosensor. An aluminum surface passivation
treatment based on oxygen plasma is developed in order to circumvent the
undesired effects of oxidation and corrosion usually found in aluminum-based
biosensors. Immersion tests in deionized water and device simulations are used to
evaluate the effectiveness of the passivation process. A label-free bioassay
based on biotin analysis through biotin-functionalized dextran-lipase conjugates
immobilized on the biosensor-passivated surface in aqueous media is performed as
a proof of concept to demonstrate the suitability of these nanostructured
aluminum films for biosensing.
PMID- 24354281
TI - Self-assembly of high molecular weight polypeptide copolymers studied via
diffusion limited aggregation.
AB - The assembly of high molecular weight polypeptides into complex architectures
exhibiting structural complexity ranging from the nano- to the mesoscale is of
fundamental importance for various protein-related diseases but also hold great
promise for various nano- and biotechnological applications. Here, the
aggregation of partially unfolded high molecular weight polypeptides into
multiscale fractal structures is investigated by means of diffusion limited
aggregation and atomic force microscopy. The zeta potential, the hydrodynamic
radius, and the obtained fractal morphologies were correlated with the
conformation of the polypeptide backbones as obtained from circular dichroism
measurements. The polypeptides are modified with polyethylene oxide side chains
to stabilize the polypeptides and to normalize intermolecular interactions. The
modification with the hydrophobic thioctic acid alters the folding of the
polypeptide backbone, resulting in a change in solution aggregation and fractal
morphology. We found that a more compact folding results in dense and highly
branched structures, whereas a less compact folded polypeptide chain yields a
more directional assembly. Our results provide first evidence for the role of
compactness of polypeptide folding on aggregation. Furthermore, the mesoscale
structured biofilms were used to achieve a hierarchical protein assembly, which
is demonstrated by deposition of Rhodamine-labeled HSA with the preassembled
fractal structures. These results contribute important insights to the
fundamental understanding of the aggregation of high molecular weight
polypeptides in general and provide opportunities to study nanostructure-related
effects on biological systems such as adhesion, proliferation, and the
development of, for example, neuronal cells.
PMID- 24354282
TI - Water-responsive mechanically adaptive nanocomposites based on styrene-butadiene
rubber and cellulose nanocrystals--processing matters.
AB - Biomimetic, stimuli-responsive polymer nanocomposites based on a hydrophobic
styrene-butadiene rubber (SBR) matrix and rigid, rod-like cellulose nanocrystals
(CNCs) isolated from cotton were prepared by three different approaches, and
their properties were studied and related to the composition, processing history,
and exposure to water as a stimulus. The first processing approach involved
mixing an aqueous SBR latex with aqueous CNC dispersions, and films were
subsequently formed by solution-casting. The second method utilized the first
protocol, but films were additionally compression-molded. The third method
involved the formation of a CNC organogel via a solvent exchange with acetone,
followed by infusing this gel, in which the CNCs form a percolating network with
solutions of SBR in tetrahydrofuran. The thermomechanical properties of the
materials were established by dynamic mechanical thermal analysis (DMTA). In the
dry state, all nanocomposites show much higher tensile storage moduli, E', than
the neat SBR or the SBR latex. E' increases with the CNC content and depends
strongly on the processing method, which appears to influence the morphology of
the SBR nanocomposites produced. The highest E' values were observed for the
solution cast samples involving an SBR latex, where E' increased from 3 MPa for
the neat SBR to ca. 740 MPa for the nanocomposite containing 20% v/v CNCs. Upon
submersion in deionized water, a dramatic reduction of E' was observed, for
example from 740 to 5 MPa for the solution-cast nanocomposite containing 20% v/v
CNCs. This change is interpreted as a disengagement of the percolating CNC
network, on account of modest aqueous swelling and competitive hydrogen bonding
of water molecules with the CNCs. It is shown that the method of preparation also
influenced the swelling behavior and kinetics of modulus switching, consistent
with different arrangements of the CNCs, which serve as channels for water
absorption and transport within the hydrophobic SBR matrix.
PMID- 24354283
TI - Spatially resolved in situ measurements of the ion distribution near the surface
of electrode in a steady-state diffusion in an electrolytic tank with confocal
micro X-ray fluorescence.
AB - Confocal micro-X-ray fluorescence (MXRF) technology based on a polycapillary
focusing X-ray lens and a polycapillary parallel X-ray lens was used to carry out
element-resolved and in situ analysis of ion distribution near the surface of the
electrode in a steady-state diffusion in an electrolytic tank. The standard curve
of the Cu Kalpha fluorescence intensity corresponding to the concentration of
CuCl2 was measured to quantitatively determine the ion distribution near the
surface of the electrode in a steady-state diffusion. The distribution of the
electrolytic ions around the surface of the electrode in the electrolytic tank
was measured in situ, and the effects of the concentration of the electrolyte and
the bath voltage on the shape of the layer with a nonuniform distribution of the
Cu(2+) ions near the cathode surface in a steady state were analyzed with the
confocal MXRF. The confocal MXRF has potential applications in spatially resolved
analysis of the liquid mass transfer in electrolytic tanks in situ.
PMID- 24354284
TI - Polypeptoid-block-polypeptide copolymers: synthesis, characterization, and
application of amphiphilic block Copolypept(o)ides in drug formulations and
miniemulsion techniques.
AB - We report the synthesis of polysarcosine-block-polyglutamic acid benzylester
(PSar-block-PGlu(OBn)) and polysarcosine-block-polylysine-epsilon-N
benzyloxycarbonyl (PSar-block-PLys(Z)) copolymers. The novel polypeptoid-block
polypeptide copolymers (Copolypept(o)ides) have been synthesized by ring-opening
polymerization (ROP) of N-carboxyanhydrides (NCAs). Polymerization conditions
were optimized regarding protecting groups, block sequence and length. While the
degree of polymerization of the PSar block length was set to be around 200 or
400, PGlu(OBn) and PLys(Z) block lengths were varied between 20 to 75. The
obtained block copolymers had a total degree of polymerization of 220-475 and
dispersity indices between 1.1 and 1.2. Having ensured a nontoxic behavior up to
a concentration of 3 mg/mL in HEK293 cells, the novel block copolymers have been
applied to the synthesis of organic colloids (by miniemulsion polymerization and
miniemulsion solvent evaporation process). Colloids of around 100 nm
(miniemulsion polymerization) to 200 nm (miniemulsion process) have been
prepared. Additionally, PSar-block-PGlu(OBn) copolymers have been used in a drug
formulation of an adenylate cyclase inhibitor. Micelles of 28.0 nm (without drug)
and 33.0 nm (with drug) diameter have been observed by fluorescence correlation
spectroscopy (FCS). The polypeptoid-block-polypeptide formulation increased
solubility of the drug and enhances its bioavailability, which leads to a
reduction of intracellular cAMP levels in MaMel 91 melanoma cells.
PMID- 24354285
TI - Multifunctional g-C(3)N(4) nanofibers: a template-free fabrication and enhanced
optical, electrochemical, and photocatalyst properties.
AB - We have developed a facile, scale up, and efficient method for the preparation of
graphitic-C3N4 nanofibers (GCNNFs) as electrodes for supercapacitors and
photocatalysts. The as-synthesized GCNNFs have 1D structure with higher
concentration of nitrogen that is favorable for higher conductivity and
electrochemical performance. Secondly, the high surface area of GCNNF provides a
large electrode-electrolyte contact area, sufficient light harvesting and mass
transfer, as well as increased redox potential. Thus, the GCNNF supercapacitor
electrode shows high capacitance of 263.75 F g(-1) and excellent cyclic stability
in 0.1 M Na2SO4 aqueous electrolyte with the capacitance retention of 93.6% after
2000 cycles at 1 A g(-1) current density. GCNNFs exhibit high capacitance of 208
F g(-1) even at 10 A g(-1), with the appreciable capacitance retention of 89.5%,
which proves its better rate capability. Moreover, the GCNNF shows enhanced
photocatalytic activity in the photodegradation of RhB in comparison to the bulk
graphitic-C3N4 (GCN). The degradation rate constant of GCNNF photocatalyst is
almost 4 times higher than GCN. The enhanced photocatalytic activity of GCNNF is
mainly due to the higher surface area, appropriate bandgap, and fewer defects in
GCNNF as compared to GCN. As an economical precursor (melamine) and harmless,
facile, and template-free synthesis method with excellent performance both in
supercapacitors and in photodegradation, GCNNF is a strong candidate for energy
storage and environment protection applications.
PMID- 24354290
TI - Chemical Biology Consortium Sweden.
PMID- 24354286
TI - Ligand-independent and tissue-selective androgen receptor inhibition by
pyrvinium.
AB - Pyrvinium pamoate (PP) is a potent noncompetitive inhibitor of the androgen
receptor (AR). Using a novel method of target identification, we demonstrate that
AR is a direct target of PP in prostate cancer cells. We demonstrate that PP
inhibits AR activity via the highly conserved DNA binding domain (DBD), the only
AR inhibitor that functions via this domain. Furthermore, computational modeling
predicts that pyrvinium binds at the interface of the DBD dimer and the minor
groove of the AR response element. Because PP acts through the DBD, PP is able to
inhibit the constitutive activity of AR splice variants, which are thought to
contribute to the growth of castration resistant prostate cancer (CRPC). PP also
inhibits androgen-independent AR activation by HER2 kinase. The antiandrogen
activity of pyrvinium manifests in the ability to inhibit the in vivo growth of
CRPC xenografts that express AR splice variants. Interestingly, PP was most
potent in cells with endogenous AR expression derived from prostate or bone. PP
was able to inhibit several other hormone nuclear receptors (NRs) but not
structurally unrelated transcription factors. PP inhibition of other NRs was
similarly cell-type selective. Using dual-energy X-ray absorptiometry, we
demonstrate that the cell-type specificity of PP manifests in tissue-selective
inhibition of AR activity in mice, as PP decreases prostate weight and bone
mineral density but does not affect lean body mass. Our results suggest that the
noncompetitive AR inhibitor pyrvinium has significant potential to treat CRPC,
including cancers driven by ligand-independent AR signaling.
PMID- 24354291
TI - Numerical model investigation for potential methane explosion and benzene vapor
intrusion associated with high-ethanol blend releases.
AB - Ethanol-blended fuel releases usually stimulate methanogenesis in the subsurface,
which could pose an explosion risk if methane accumulates in a confined space
above the ground where ignitable conditions exist. Ethanol-derived methane may
also increase the vapor intrusion potential of toxic fuel hydrocarbons by
stimulating the depletion of oxygen by methanotrophs, and thus inhibiting aerobic
biodegradation of hydrocarbon vapors. To assess these processes, a three
dimensional numerical vapor intrusion model was used to simulate the degradation,
migration, and intrusion pathway of methane and benzene under different site
conditions. Simulations show that methane is unlikely to build up to pose an
explosion hazard (5% v/v) if diffusion is the only mass transport mechanism
through the deeper vadose zone. However, if methanogenic activity near the source
zone is sufficiently high to cause advective gas transport, then the methane
indoor concentration may exceed the flammable threshold under simulated
conditions. During subsurface migration, methane biodegradation could consume
soil oxygen that would otherwise be available to support hydrocarbon degradation,
and increase the vapor intrusion potential for benzene. Vapor intrusion would
also be exacerbated if methanogenic activity results in sufficiently high
pressure to cause advective gas transport in the unsaturated zone. Overall, our
simulations show that current approaches to manage the vapor intrusion risk for
conventional fuel released might need to be modified when dealing with some high
ethanol blend fuel (i.e., E20 up to E95) releases.
PMID- 24354293
TI - Speciation without chromatography using selective hydride generation: inorganic
arsenic in rice and samples of marine origin.
AB - Because of the toxicity of inorganic arsenic (iAs), only iAs needs to be
monitored in food and feedstuff. This demands the development of easy and quick
analytical methods to screen large number of samples. This work focuses on
hydride generation (HG) coupled with an ICPMS as an arsenic detector where the HG
is added as a selective step to determine iAs in the gaseous phase while
organically bound As remains in the solution. iAs forms volatile arsine species
with high efficiency when treated with NaBH4 at acidic conditions, whereas most
other organoarsenic compounds do not form any or only less volatile arsines.
Additionally, using high concentrations of HCl further reduces the production of
the less volatile arsines and iAs is almost exclusively formed, therefore
enabling to measure iAs without a prior step of species separation using
chromatography. Here, we coupled a commercially available HG system to an ICPMS
and optimized for determination of iAs in rice and samples of marine origin using
different acid concentrations, wet and dry plasma conditions, and different
reaction gas modes. Comparing this method to conventional HPLC-ICPMS, no
statistical difference in iAs concentration was found and comparable limits of
detections were achieved using less than half the instrument time.
PMID- 24354292
TI - Real-time monitoring of membrane-protein reconstitution by isothermal titration
calorimetry.
AB - Phase diagrams offer a wealth of thermodynamic information on aqueous mixtures of
bilayer-forming lipids and micelle-forming detergents, providing a
straightforward means of monitoring and adjusting the supramolecular state of
such systems. However, equilibrium phase diagrams are of very limited use for the
reconstitution of membrane proteins because of the occurrence of irreversible,
unproductive processes such as aggregation and precipitation that compete with
productive reconstitution. Here, we exemplify this by dissecting the effects of
the K(+) channel KcsA on the process of bilayer self-assembly in a mixture of
Escherichia coli polar lipid extract and the nonionic detergent octyl-beta-d
glucopyranoside. Even at starting concentrations in the low micromolar range,
KcsA has a tremendous impact on the supramolecular organization of the system,
shifting the critical lipid/detergent ratios at the onset and completion of
vesicle formation by more than 2-fold. Thus, equilibrium phase diagrams obtained
for protein-free lipid/detergent mixtures would be misleading when used to guide
the reconstitution process. To address this issue, we demonstrate that, even
under such nonequilibrium conditions, high-sensitivity isothermal titration
calorimetry can be exploited to monitor the progress of membrane-protein
reconstitution in real time, in a noninvasive manner, and at high resolution to
yield functional proteoliposomes with a narrow size distribution for further
downstream applications.
PMID- 24354294
TI - Role of decision support system for renewable energy outreach.
PMID- 24354295
TI - Quantitative measurement of acetyl fentanyl and acetyl norfentanyl in human urine
by LC-MS/MS.
AB - Opioid abuse involving emerging opioid compounds is a growing public health
problem, which was highlighted recently by cases of human morbidity and mortality
linked to acetyl fentanyl abuse. Unfortunately, the lack of information available
on the toxicology and metabolism of acetyl fentanyl precludes its detection in
human samples. The following study was conducted to test a new analytical
procedure for the simultaneous quantification of acetyl fentanyl and its
predicted metabolite, acetyl norfentanyl, in human urine. Metabolic reference
standards and deuterium-labeled internal standards were synthesized for use in an
assay that coupled solid-phase extraction (SPE) with liquid chromatography-tandem
mass spectrometry (LC-MS/MS). The accuracy (% Relative Error <5%) and inter- and
intrarun precision (%CV <20%) of this new method resulted in low levels of
quantification (~1 ng/mL). Similar results were obtained using liquid
chromatography columns manufactured with phenyl-hexyl and biphenyl stationary
phases (r(2) > 0.98). Preliminary human liver microsomal and in vivo rodent
studies demonstrated that acetyl fentanyl is metabolized by cytochrome P450s to
acetyl norfentanyl. Urine samples from rats treated with a toxic dose of acetyl
fentanyl contained high concentrations of acetyl fentanyl and acetyl norfentanyl.
Further toxicokinetic studies are required to fully elucidate the metabolic
pathways responsible for acetyl fentanyl detoxification and excretion.
PMID- 24354296
TI - Incorporating isolated molybdenum (Mo) atoms into bilayer epitaxial graphene on
4H-SiC(0001).
AB - The atomic structures and electronic properties of isolated Mo atoms in bilayer
epitaxial graphene (BLEG) on 4H-SiC(0001) are investigated by low temperature
scanning tunneling microscopy (LT-STM). LT-STM results reveal that isolated Mo
dopants prefer to substitute C atoms at alpha-sites and preferentially locate
between the graphene bilayers. First-principles calculations confirm that the
embedding of single Mo dopants within BLEG is energetically favorable as compared
to monolayer graphene. The calculated band structures show that Mo-incorporated
BLEG is n-doped, and each Mo atom introduces a local magnetic moment of 1.81 MUB
into BLEG. Our findings demonstrate a simple and stable method to incorporate
single transition metal dopants into the graphene lattice to tune its electronic
and magnetic properties for possible use in graphene spin devices.
PMID- 24354297
TI - Structural changes in iron oxide and gold catalysts during nucleation of carbon
nanotubes studied by in situ transmission electron microscopy.
AB - We report a simple, versatile in situ transmission electron microscopy (TEM)
approach for investigating the nucleation and growth mechanism of carbon
nanotubes (CNTs), by which the composition, phase transition, and physical state
of various catalysts can be clearly resolved. In our approach, catalyst
nanoparticles (NPs) are placed in a multiwall CNT "tubular furnace" with two open
ends, and a high temperature is obtained by Joule heating in the specimen chamber
of a TEM. The carbon is supplied by electron irradiation-induced injection of
carbon atoms. Comparative studies on the catalytic behavior of traditional iron
oxide and recently discovered gold catalysts were performed. It was found that
the growth of CNTs from iron oxide involves the reduction of Fe2O3 to Fe3C,
nucleation and growth of CNTs from partially liquefied Fe3C, and finally the
formation of elemental Fe when the growth stops. In contrast, while changes in
shape, size, and orientation were also observed for the fluctuating Au NPs, no
chemical reactions or phase transitions occurred during the nucleation of CNTs.
These two distinct nucleation and growth processes and mechanisms would be
valuable for the structure-controlled growth of CNTs by catalyst design and
engineering.
PMID- 24354298
TI - Identification of allosteric nucleotide sites of tetramethylrhodamine-labeled
aptamer for noncompetitive aptamer-based fluorescence anisotropy detection of a
small molecule, ochratoxin A.
AB - Aptamer-based fluorescence anisotropy (FA) assay combines the advantages of
affinity aptamers in good stability, easy generation, and facile labeling and the
benefits of FA in homogeneous analysis, such as robustness, simplicity, and high
reproducibility. By using a fluorophore-labeled aptamer, FA detection of a small
molecule is not as easy as detection of protein because the binding of a small
molecule cannot cause significant increase of molecular weight of the dye-labeled
aptamer. The intramolecular interaction between labeled tetramethylrhodamine
(TMR) and DNA aptamer bases dramatically affects the local rotation and FA of
TMR. This intramolecular interaction can be altered by aptamer conformation
change upon target binding, leading to a significant change of FA of TMR. Taking
this unique feature of a TMR-labeled aptamer, we described a noncompetitive
aptamer-based fluorescence anisotropy assay for detection of small molecules by
using ochratoxin A (OTA) as a model. We successfully identified the specific TMR
labeling sites of aptamers with sensitive FA response to OTA from the 5'-end, 3'
end and the internal thymine (T) bases. The aptamer with a TMR labeled on the
10th T base exhibited a remarkable FA reduction response to OTA (Deltar = 0.078),
without requiring any proteins or nanomaterials as FA signal enhancers. This FA
approach for OTA showed high sensitivity with a detection limit of 3 nM, a
dynamic range from 3 nM to 3 MUM, and good selectivity over the tested compounds
with similar structures to OTA. The new strategy allowed the detection of OTA in
diluted red wine and urine samples.
PMID- 24354299
TI - Decoupling analysis and socioeconomic drivers of environmental pressure in China.
AB - China's unprecedented change offers a unique opportunity for uncovering
relationships between economic growth and environmental pressure. Here we show
the trajectories of China's environmental pressure and reveal underlying
socioeconomic drivers during 1992-2010. Mining and manufacturing industries are
the main contributors to increasing environmental pressure from the producer
perspective. Changes in urban household consumption, fixed capital formation, and
exports are the main drivers from the consumer perspective. While absolute
decoupling is not realized, China has in general achieved relative decoupling
between economic growth and environmental pressure. China's decoupling
performance has four distinguishable periods, closely aligning with nation-wide
major policy adjustments, which indicates significant impact of China's national
socioeconomic policies on its environmental pressure. Material intensity change
is the main contributor to the mitigation of environmental pressure, except for
ammonia nitrogen, solid wastes, aquatic Cu, and aquatic Zn. Production structure
change is the largest contributor to mitigate ammonia nitrogen emissions, and
final demand structure change is the largest contributor to mitigate emissions of
solid wastes, aquatic Cu, and aquatic Zn. We observe materialization trends for
China's production structure and final demand structure during 2002-2007.
Environmental sustainability can only be achieved by timely technology innovation
and changes of production structure and consumption pattern.
PMID- 24354300
TI - Photothermoelectric effect in suspended semiconducting carbon nanotubes.
AB - We have performed scanning photocurrent microscopy measurements of field-effect
transistors (FETs) made from individual ultraclean suspended carbon nanotubes
(CNTs). We investigate the spatial-dependence, polarization-dependence, and gate
dependence of photocurrent and photovoltage in this system. While previous
studies of surface-bound CNT FET devices have identified the photovoltaic effect
as the primary mechanism of photocurrent generation, our measurements show that
photothermoelectric phenomena play a critical role in the optoelectronic
properties of suspended CNT FETs. We have quantified the photothermoelectric
mechanisms and identified regimes where they overwhelm the photovoltaic
mechanism.
PMID- 24354301
TI - Trypsin-catalyzed N-terminal labeling of peptides with stable isotope-coded
affinity tags for proteome analysis.
AB - An enzymatic approach to label peptide N-termini with isotope-coded affinity tags
is presented. This method exploits the high activity of trypsin for peptide
synthesis in organic solvents. A cosubstrate containing a stable isotope-coded
Arg residue and a biotin tag was synthesized. When the cosubstrate was incubated
with tryptic peptides and trypsin in ethanol solution, the stable isotope-coded
affinity tag was specifically coupled onto the N-termini of peptides via the
formation of new peptide bonds. The labeled peptides were specifically enriched
by avidin affinity chromatography and then were submitted to liquid
chromatography-tandem mass spectrometry (LC/MS/MS) for quantification. This
enrichment step effectively reduced the interference by unlabeled peptides. The
excellent performance of this approach was demonstrated by labeling standard
peptides as well as a mouse liver digest. In addition to one amino acid residue,
a few dipeptide tags were also introduced to the N-termini of peptides
successfully by this enzymatic approach. It was found that the identifications
for samples labeled with these tags were highly complementary. Coupling a short
sequence tag onto peptides could be an effective approach to improve the coverage
for proteome analysis.
PMID- 24354302
TI - Noninvasive measurement of membrane potential modulation in microorganisms:
photosynthesis in green algae.
AB - Cell membrane potential (CMP) modulation is a physical measurement to
quantitatively probe cell physiology in real time at high specificity.
Electrochemical field effect transistors (eFETs) made from graphene and Si
nanowire provide strong mechanical and electrical coupling with neurons and
muscle cells to noninvasively measure CMP at high sensitivity. To date, there are
no noninvasive methods to study electrophysiology of microorganisms because of
stiff cell walls and significantly smaller membrane polarizations. An eFET made
from the smallest possible nanostructure, a nanoparticle, with sensitivity to a
single-electron charge is developed to noninvasively measure CMP modulation in
algae. The applicability of the device is demonstrated by measuring CMP
modulation due to a light-induced proton gradient inside the chloroplast during
photosynthesis. The ~9 mV modulation in CMP in algae is consistent with the
absorbance spectrum of chlorophyll, photosynthetic pathway, and inorganic carbon
source concentration in the environment. The method can potentially become a
routine method to noninvasively study electrophysiology of cells, such as
microorganisms for biofuels.
PMID- 24354303
TI - Focus: a robust workflow for one-dimensional NMR spectral analysis.
AB - One-dimensional (1)H NMR represents one of the most commonly used analytical
techniques in metabolomic studies. The increase in the number of samples analyzed
as well as the technical improvements involving instrumentation and spectral
acquisition demand increasingly accurate and efficient high-throughput data
processing workflows. We present FOCUS, an integrated and innovative methodology
that provides a complete data analysis workflow for one-dimensional NMR-based
metabolomics. This tool will allow users to easily obtain a NMR peak feature
matrix ready for chemometric analysis as well as metabolite identification scores
for each peak that greatly simplify the biological interpretation of the results.
The algorithm development has been focused on solving the critical difficulties
that appear at each data processing step and that can dramatically affect the
quality of the results. As well as method integration, simplicity has been one of
the main objectives in FOCUS development, requiring very little user input to
perform accurate peak alignment, peak picking, and metabolite identification. The
new spectral alignment algorithm, RUNAS, allows peak alignment with no need of a
reference spectrum, and therefore, it reduces the bias introduced by other
alignment approaches. Spectral alignment has been tested against previous
methodologies obtaining substantial improvements in the case of moderate or
highly unaligned spectra. Metabolite identification has also been significantly
improved, using the positional and correlation peak patterns in contrast to a
reference metabolite panel. Furthermore, the complete workflow has been tested
using NMR data sets from 60 human urine samples and 120 aqueous liver extracts,
reaching a successful identification of 42 metabolites from the two data sets.
The open-source software implementation of this methodology is available at
http://www.urr.cat/FOCUS.
PMID- 24354304
TI - Method for obtaining silver nanoparticle concentrations within a porous medium
via synchrotron X-ray computed microtomography.
AB - Attempts at understanding nanoparticle fate and transport in the subsurface
environment are currently hindered by an inability to quantify nanoparticle
behavior at the pore scale (within and between pores) within realistic pore
networks. This paper is the first to present a method for high resolution
quantification of silver nanoparticle (nAg) concentrations within porous media
under controlled experimental conditions. This method makes it possible to
extract silver nanoparticle concentrations within individual pores in static and
quasi-dynamic (i.e., transport) systems. Quantification is achieved by employing
absorption-edge synchrotron X-ray computed microtomography (SXCMT) and an
extension of the Beer-Lambert law. Three-dimensional maps of X-ray mass linear
attenuation are converted to SXCMT-determined nAg concentration and are found to
closely match the concentrations determined by ICP analysis. In addition, factors
affecting the quality of the SXCMT-determined results are investigated: 1) The
acquisition of an additional above-edge data set reduced the standard deviation
of SXCMT-determined concentrations; 2) X-ray refraction at the grain/water
interface artificially depresses the SXCMT-determined concentrations within 18.1
MUm of a grain surface; 3) By treating the approximately 20 * 10(6) voxels within
each data set statistically (i.e., averaging), a high level of confidence in the
SXCMT-determined mean concentrations can be obtained. This novel method provides
the means to examine a wide range of properties related to nanoparticle transport
in controlled laboratory porous medium experiments.
PMID- 24354305
TI - Lanthanide-functionalized nanoparticles as MRI and luminescent probes for sensing
and/or imaging applications.
AB - The combination of lanthanides and nanoparticles to develop new hybrid
nanomaterials has become a highly topical area of research in the field of
sensing, biomedical imaging, drug delivery, etc. However, these novel
nanomaterials have to be carefully designed to ensure that the unique properties
conveyed by each component, i.e., lanthanide ions and nanoparticles, are
maximized and not negatively affected by one another. In this Forum Article, the
main advances in the design of lanthanide-based nanoparticles will be discussed,
with the first part focusing on the design of gadolinium(III)-based nanoparticles
and their use as magnetic resonance imaging agents. The second part will then
describe the main and most recent designs of luminescent lanthanide-based
nanoparticles and their applications as sensors or imaging agents, with a special
emphasis on our contribution to this area.
PMID- 24354306
TI - Influence of the coordination environment of zinc(II) complexes of designed
Mannich ligands on phosphatase activity: a combined experimental and theoretical
study.
AB - A mononucleating (HL(1)) and a dinucleating (HL(2)) "end-off" compartmental
ligand have been designed and synthesized by controlled Mannich reaction using p
cresol and bis(2-methoxyethyl)amine, and their formation has been rationalized.
Six complexes have been prepared on treating HL(1) and HL(2) with Zn(II)X2 (X =
Cl(-), Br(-), I(-)) with the aim to investigate their hydrolytic activity on
phosphoester bond cleavage. Interestingly, the mononucleating ligand was observed
to yield dinuclear complexes, [Zn2(L(1))2X2] (1-3), while the potential
dinucleating ligand generated mononuclear complexes, [Zn(HL(2))X2] (4-6). Four (1
4), out of six complexes studied, were characterized by single-crystal X-ray
diffraction (XRD): the Zn ion exhibits trigonal bipyramidal and tetrahedral
coordination spheres in the di- and mononuclear complex, respectively. The
hydrolytic kinetics, followed spectrophotometrically with 4-nitrophenylphosphate
(4-NPP) in buffered dimethylformamide (DMF) (97.5% DMF, v/v) because of
solubility reasons, under excess substrate conditions (substrate:complex = 20:1),
indicated that the complexes enormously accelerate the rate of phosphomonoester
hydrolysis with first order rate constants (kcat) in the range 2-10 s(-1) at 25
degrees C. In each case kinetic data analyses have been run by Michaelis-Menten
treatment. The efficacy in the order of conversion of substrate to product (p
nitrophenolate ion) follows the trend 1 > 2 > 3 > 4 > 5 > 6, and the ratio of
kcat of an analogous dinuclear to mononuclear complex is ?2. An electrospray
ionization-mass spectrometry (ESI-MS) study has revealed the dissociation of the
centrosymmetric dinuclear complex to two mononuclear species instead of a syn
cooperative catalysis. Density functional theory (DFT) calculations have been
performed to rationalize our proposed mechanistic pathway for phosphatase
activity. The comparative analysis concludes the following facts under
experimental conditions: (1) the halide bound to the active site affects the
overall rate in the order: Cl(-) > Br(-) > I(-) regardless of nuclearity; (2)
dinuclear complexes prevail over the mononuclear ones.
PMID- 24354308
TI - Solution-chemical route to generalized synthesis of metal germanate nanowires
with room-temperature, light-driven hydrogenation activity of CO2 into renewable
hydrocarbon fuels.
AB - A facile solution-chemical route was developed for the generalized preparation of
a family of highly uniform metal germanate nanowires on a large scale. This route
is based on the use of hydrazine monohydrate/H2O as a mixed solvent under
solvothermal conditions. Hydrazine has multiple effects on the generation of the
nanowires: as an alkali solvent, a coordination agent, and crystal anisotropic
growth director. Different-percentage cobalt-doped Cd2Ge2O6 nanowires were also
successfully obtained through the addition of Co(OAc)2.4H2O to the initial
reaction mixture for future investigation of the magnetic properties of these
nanowires. The considerably negative conduction band level of the Cd2Ge2O6
nanowire offers a high driving force for photogenerated electron transfer to CO2
under UV-vis illumination, which facilitates CO2 photocatalytic reduction to a
renewable hydrocarbon fuel in the presence of water vapor at room temperature.
PMID- 24354307
TI - Change in drusen volume as a novel clinical trial endpoint for the study of
complement inhibition in age-related macular degeneration.
AB - BACKGROUND AND OBJECTIVE: To evaluate the change in drusen volume following
treatment with eculizumab, a systemic inhibitor of complement component 5.
PATIENTS AND METHODS: Single-center, prospective, randomized, double-masked
clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or
placebo over 26 weeks. MAIN OUTCOME MEASURE: decrease in drusen volume of at
least 50% at 26-week follow-up. RESULTS: Mean drusen cube root volumes were 0.49
mm and 0.47 mm (P = .64) at baseline and 0.51 mm and 0.42 mm (P = .17) at 26
weeks in the eculizumab and placebo groups, respectively. In the placebo group,
one eye had a decrease in drusen volume of at least 50% and two eyes developed
neovascularization through 26 weeks. CONCLUSION: Systemic complement inhibition
with eculizumab did not significantly reduce drusen volume. Drusen growth was
dependent on the number of complement at-risk alleles. Future trials should
consider the use of a composite clinical trial endpoint in which efficacy is
defined by the treatment's ability to prevent drusen growth, neovascularization,
and the formation of geographic atrophy over 1 year.
PMID- 24354309
TI - Identification and characterization of dimeric oxidation products of p-cymene-2,3
diol isolated from Thymus vulgaris L.
AB - The aim of this study was to investigate the oxidation products of p-cymene-2,3
diol, a major antioxidative constituent of thyme (Thymus vulgaris L.). Although a
dimeric form of p-cymene-2,3-diol and some derivative substances exhibiting
valuable food technological and health-promoting properties have been reported in
earlier publications, no obvious correlation has been shown between these
substances. A modified HPLC-ESI-MS method made it possible to prove that two
dimers, 3,4,3',4'-tetrahydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (1) and the
newly identified 3',4'-dihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl-3,4-dione
(2), are oxidation products of p-cymene-2,3-diol. 2 was characterized by the
fragmentation pattern determined by multiple mass spectrometry, (1)H NMR, (13)C
NMR, H-H COSY, HSQC, and HMBC. Both biphenyls were also quantitated in freeze
dried thyme as well as in a food matrix spiked with thyme extract. Model
experiments using raw and cooked minced pork meat as matrix and sodium nitrite as
oxidizing and reduction agent with and without ascorbic acid as protective
reagent showed the correlation between food processing and dimer generation.
PMID- 24354310
TI - Double-sided brush-shaped TiO2 nanostructure assemblies with highly ordered
nanowires for dye-sensitized solar cells.
AB - We describe a seeded hydrothermal process for the growth of unique double-sided
brush-shaped (DSBS) TiO2 nanostructure assemblies consisting of highly ordered
rutile nanowires vertically aligned around an annealed TiO2 nanoparticle layer.
The annealed TiO2 nanoparticle layer seeds the nanowire growth and also supports
the DSBS structure. The morphology of the DSBS TiO2 nanostructure depends on the
hydrothermal reaction time. The diameter of the nanowires is about 6.6 nm, and
with increasing reaction time from 1 to 8 h the nanowire length increases from
0.6 to 6.2 MUm, whereas the thickness of the nanoparticle layer decreases from
4.3 to 2.8 MUm. These free-standing nanowire arrays provide large internal
surface area, which is essential for minimizing carrier recombination in high
performance photovoltaic devices. Furthermore, the nanowire architecture can help
increase the rate of charge transport as compared to particulate films because of
lower concentration of grain boundaries. The power conversion efficiency of
backside (DSBS TiO2/FTO photoanode) illuminated dye-sensitized solar cells
fabricated using the DSBS TiO2 nanostructure assembly is found to be depended on
the nanowire length. A cell fabricated using 15.2 MUm thick nanostructures
sensitized by N719 has a short-circuit current density of 12.18 mA cm(-2), 0.78 V
open circuit potential, and a 0.59 filling factor, yielding a maximum power
conversion efficiency of 5.61% under AM 1.5 illumination.
PMID- 24354311
TI - Calix[4]arene-supported mononuclear lanthanide single-molecule magnet.
AB - Three new single paramagnetic lanthanide-based complexes, [Ln(L)(LOEt)] (Ln(3+) =
Dy(3+), Tb(3+), and Ho(3+)), are synthesized with the multidentate calix[4]arene
ligand H2L (H2L = 5,11,17,23-tetrakis(1,1-dimethylethyl)-25,27-dihydroxy-26,28
dimethoxycalix[4]arene) and Klaui's tripodal ligand LOEt(-) (LOEt(-) = (eta(5)
cyclopentadienyl)tris(diethylphosphito-p)cobaltate(III)). All of the complexes
have been characterized by single crystal X-ray diffraction analysis, thermal
stability, absorption spectra, and magnetization measurements. The magnetic
properties and magnetostructural correlation in this seven-coordinated system are
investigated. The dysprosium complex 1 shows typical single-molecule magnetic
behavior with characteristic magnetic hysteresis loops and the slow relaxation of
magnetization.
PMID- 24354312
TI - Proton-induced reversible modulation of the luminescent output of rhenium(I),
iridium(III), and ruthenium(II) tetrazolate complexes.
AB - One of the distinct features of metal-tetrazolate complexes is the possibility of
performing electrophilic additions onto the imine-type nitrogens of the
coordinated five-membered ring. These reactions, in particular, provide a useful
tool for varying the main structural and electronic properties of the starting
tetrazolate complexes. In this paper, we demonstrate how the use of a simple
protonation-deprotonation protocol enables us to reversibly change, to a
significant extent, the light-emission output and performance of a series of
Re(I)-tetrazolate-based phosphors of the general formulation fac
[Re(N(?)N)(CO)3L], where N(?)N denotes diimine-type ligands such as 2,2'
bipyridine (bpy) or 1,10-phenanthroline (phen) and L represents a series of
different 5-aryl tetrazolates. Indeed, upon addition of triflic acid to these
neutral Re(I) complexes, a consistent blue shift (Deltalambdamax ca. 50 nm) of
the emission maximum is observed and the protonated species also display
increased quantum yield values (4-13 times greater than the starting compounds)
and longer decay lifetimes. This alteration can be reversed to the initial
condition by further treating the protonated Re(I) complex with a base such as
triethylamine. Interestingly, the reversible modulation of luminescent features
by the same protonation-deprotonation mechanism appears as a quite general
characteristic of photoactive metal tetrazolate complexes, even for compounds in
which the 2-pyridyl tetrazolate ligands coordinate the metal center with a
bidentate mode, such as the corresponding Ir(III) cyclometalates [Ir(C(?)N)2L]
and the Ru(II) polypyridyl derivatives [Ru(bpy)2L](+). In these cases, the
protonation of the starting materials leads to red-shifted and more intense
emissions for the Ir(III) complexes, while almost complete quenching is observed
in the case of the Ru(II) analogues.
PMID- 24354313
TI - Predicting the antinociceptive efficacy of sigma(1) receptor ligands by a novel
receptor fluorescence resonance energy transfer (FRET) based biosensor.
AB - We have developed a novel methodology for monitoring the sigma1 receptor
activation switch in living cells. Our assay uncovered the intrinsic nature of
sigma1 receptor ligands by recording the ligand-mediated conformational changes
of this chaperone protein. The change triggered by each ligand correlated well
with its ability to attenuate formalin induced nociception in an animal model of
pain. This tool may assist in predicting the antinociceptive efficacy of sigma1
receptor ligands.
PMID- 24354314
TI - Complex logic functions implemented with quantum dot bionanophotonic circuits.
AB - We combine quantum dots (QDs) with long-lifetime terbium complexes (Tb), a near
IR Alexa Fluor dye (A647), and self-assembling peptides to demonstrate
combinatorial and sequential bionanophotonic logic devices that function by time
gated Forster resonance energy transfer (FRET). Upon excitation, the Tb-QD-A647
FRET-complex produces time-dependent photoluminescent signatures from multi-FRET
pathways enabled by the capacitor-like behavior of the Tb. The unique
photoluminescent signatures are manipulated by ratiometrically varying dye/Tb
inputs and collection time. Fluorescent output is converted into Boolean logic
states to create complex arithmetic circuits including the half-adder/half
subtractor, 2:1 multiplexer/1:2 demultiplexer, and a 3-digit, 16-combination
keypad lock.
PMID- 24354317
TI - Borole formation by 1,1-carboboration.
AB - Bis(trimethylsilylethynyl)diphenylaminoborane was reacted with the strong Lewis
acid B(C6F5)3 at ambient temperature to give the borole 9 admixed with a small
amount of its thermal follow-up product 12. Compound 9 was subsequently
stabilized by adduct formation with pyridine (10). Treatment of
bis(trimethylsilylethynyl)phenylborane with B(C6F5)3 gave the borole 14, which
reacted with 3-hexyne to give the [4 + 2] cycloaddition product 15.
PMID- 24354316
TI - Substituted 2-phenylimidazopyridines: a new class of drug leads for human African
trypanosomiasis.
AB - A phenotypic screen of a compound library for antiparasitic activity on
Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to
the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting
point for hit-to-lead medicinal chemistry. A total of 110 analogues were
prepared, which led to the identification of 64, a substituted 2-(3
aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro
with an EC50 of 2 nM and displayed reasonable druglike properties when tested in
a number of in vitro assays. The compound was orally bioavailable and displayed
good plasma and brain exposure in mice. Compound 64 cured mice infected with
Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent
antiparasitic properties and its ease of synthesis, compound 64 represents a new
lead for the development of drugs to treat human African trypanosomiasis.
PMID- 24354318
TI - Targeted Metabolomics: a new section in the Journal of Agricultural and Food
Chemistry.
PMID- 24354319
TI - Exploring the determinants of trace amine-associated receptor 1's functional
selectivity for the stereoisomers of amphetamine and methamphetamine.
AB - Amphetamines are widely abused drugs that interfere with dopamine transport and
storage. Recently, however, another mechanism of action was identified:
stereoselective activation of the GalphaS protein-coupled trace amine-associated
receptor 1 (TAAR1). To identify structural determinants of this
stereoselectivity, we functionally evaluated six mutant receptors in vitro and
then used homology modeling and dynamic simulation to predict drug affinities.
Converting Asp102 to Ala rendered mouse and rat TAAR1 (mTAAR1 and rTAAR1,
respectively) insensitive to beta-phenylethylamine, amphetamine (AMPH), and
methamphetamine (METH). Mutating Met268 in rTAAR1 to Thr shifted the
concentration-response profiles for AMPH and METH isomers rightward an order of
magnitude, whereas replacing Thr268 with Met in mTAAR1 resulted in profiles
leftward shifted 10-30-fold. Replacing Asn287 with Tyr in rTAAR1 produced a
mouselike receptor, while the reciprocal mTAAR1 mutant was rTAAR1-like. These
results confirm TAAR1 is an AMPH/METH receptor in vitro and establish residues
102 (3.32) and 268 (6.55) as major contributors to AMPH/METH binding with residue
287 (7.39) determining species stereoselectivity.
PMID- 24354320
TI - STOP-BANG questionnaire performance in a Veterans Affairs unattended sleep study
program.
AB - RATIONALE: There are no published data regarding use of the STOP-BANG sleep apnea
questionnaire in populations referred to Veterans Affairs (VA) sleep facilities.
If a particular STOP-BANG score cutpoint had high positive predictive value in
this referral population, it could reduce the need for diagnostic sleep studies.
METHODS: STOP-BANG questionnaires were prospectively administered to veterans
undergoing unattended sleep studies at a single VA facility. We evaluated the
sensitivity, specificity, positive predictive value, and area under the receiver
operating characteristic curve (ROC AUC) of STOP-BANG scores for identifying a
Respiratory Disturbance Index (RDI) greater than 15/hour. We also recalibrated
the STOP-BANG score to our referral population, using logistic regression models.
MEASUREMENTS AND MAIN RESULTS: Of 1,196 consecutive veterans undergoing
unattended sleep studies, the mean STOP-BANG score was 5.7 +/- 1.4, and 67% had
an RDI greater than 15/hour. Sensitivities were excellent at lower STOP-BANG
scores, but sharply decreased at scores of 6 and above. Specificity improved in a
linear fashion with increasing scores. The ROC AUC was 0.66 (95% confidence
interval [CI], 0.64-0.69) and recalibrated models improved the ROC AUC to 0.74
(95% CI, 0.69-0.78). The highest STOP-BANG score of 8 was present in only 7.9% of
the sample and had a positive predictive value of 85% (95% CI, 76-92%).
CONCLUSIONS: The STOP-BANG questionnaire alone is insufficient to confirm the
presence of significant sleep apnea. A maximal score of 8 did not have a high
enough positive predictive value to forego confirmatory sleep testing.
PMID- 24354321
TI - Hydroxyl-proton hydrogen bonding in the heparin oligosaccharide Arixtra in
aqueous solution.
AB - Heparin is best known for its anticoagulant activity, which is mediated by the
binding of a specific pentasaccharide sequence to the protease inhibitor
antithrombin-III (AT-III). Although heparin oligosaccharides are thought to be
flexible in aqueous solution, the recent discovery of a hydrogen bond between the
sulfamate (NHSO3(-)) proton and the adjacent 3-O-sulfo group of the 3,6-O
sulfated N-sulfoglucosamine residue of the Arixtra (fondaparinux sodium)
pentasaccharide demonstrates that definable elements of local structure are
accessed. Molecular dynamics simulations of Arixtra suggest the presence of
additional hydrogen bonds involving the C3-OH groups of the glucuronic acid and 2
O-sulfo-iduronic acid residues. NMR measurements of temperature coefficients,
chemical shift differences, and solvent exchange rate constants provide
experimental confirmation of these hydrogen bonds. We note that the extraction of
rate constants from cross-peak buildup curves in 2D exchange spectroscopy is
complicated by the presence of radiation damping in aqueous solution. A
straightforward model is presented that explicitly takes into account the effects
of radiation damping on the water proton relaxation and is sufficiently robust to
provide an accurate measure of the proton exchange rate between the analyte
hydroxyl protons and water.
PMID- 24354322
TI - Quinoline-pyrimidine hybrids: synthesis, antiplasmodial activity, SAR, and mode
of action studies.
AB - For the treatment of malaria which affects nearly 200 million people each year
and the continued exacerbation by the emergence of drug resistance to most of the
available antimalarials, the "covalent bitherapy" suggests hybrid molecules to be
the next-generation antimalarial drugs. In this investigation, new hybrids of 4
aminoquinoline and pyrimidine moieties that show antiplasmodial activity in the
nM range against chloroquine-resistant as well as chloroquine-sensitive strains
of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of
action of most potent hybrid molecule have been conducted.
PMID- 24354323
TI - Benchtop MRI for pharmacokinetic evaluation of two aqueous-based nano-scaled
formulations of oleic acid stabilized magnetite nanocrystals.
AB - BACKGROUND: The interplay between numerous factors, including the size, shape,
coating, surface charge and composition of particles is known to affect the
pharmacokinetics and biodistribution of superparamagnetic iron oxides (SPIOs).
This makes understanding the role of each factor independently quite challenging.
METHODS: In the present study, the in vivo magnetic resonance imaging (MRI),
biodistribution and hepatic clearance evaluations of two SPIOs Formulations A and
B developed from ~13.5 nm hydrophobic oleic acid stabilized monodisperse
magnetite nanocrystals core and lipid-based amphiphilic stabilizers were
performed using a prototype benchtop MR imager (22 MHz) and pulsed nuclear
magnetic resonance (NMR) system (20 MHz), respectively. Formulation A was
composed of mPEG-2000-DSPE and Formulation B was composed of Phospholipon-100H,
sucrose ester M-1695 and Cremophor RH-40. RESULTS: The in vivo MRI investigations
showed that both formulations were safe and effective as potential liver MR
contrast agents with sustained liver contrast for at least seven days. In
addition, ex vivo relaxometric investigations revealed that the formulations
predominantly distribute to the liver and spleen following I.V. injection. The
hepatic clearance kinetics determined based on the relaxometric quantification
method indicated that both formulations exhibited a biphasic clearance process
with a slow terminal clearance half-life of 11.5 and 12.7 days, respectively, for
Formulations A and B. CONCLUSIONS: The results of this study showed the potential
biomedical applications of the investigated magnetopharmaceutical formulations as
MRI contrast agents.
PMID- 24354324
TI - Phenotypic and functional plasticity of gamma-delta (gammadelta) T cells in
inflammation and tolerance.
AB - Gamma-delta T cells (gammadelta T cells) are an unique group of lymphocytes and
play an important role in bridging the gap between innate and adaptive immune
systems under homeostatic condition as well as during infection and inflammation.
They are predominantly localized into the mucosal and epithelial sites, but also
exist in other peripheral tissues and secondary lymphoid organs. gammadelta T
cells can produce cytokines and chemokines to regulate the migration of other
immune cells, can bring about lysis of infected or stressed cells by secreting
granzymes, provide help to B cells and induce IgE production, can present antigen
to conventional T cells, activate antigen presenting cells (APC) maturation, and
are also known to produce growth factors that regulate the stromal cell function.
gammadelta T cells spontaneously produce IFN-gamma and IL-17 cytokines compared
to delayed differentiation of Th1 and Th17 cells. In this review, we discussed
the current knowledge about the mechanism of gammadelta T cell function including
its mode of antigen recognition, and differentiation into various subsets of
gammadelta T cells. We also explored how gammadelta T cells interact with
different types of innate and adaptive immune cells, and how these interactions
shape the immune response highlighting the plasticity and role of these cells
protective or pathogenic under inflammatory and tolerogenic conditions.
PMID- 24354325
TI - Forkhead box P3: the peacekeeper of the immune system.
AB - Ten years ago Forkhead box P3 (FOXP3) was discovered as master gene driving
CD4(+)CD25(+) T cell regulatory (Treg) function. Since then, several layers of
complexity have emerged in the regulation of its expression and function, which
is not only exerted in Treg cells. While the mechanisms leading to the highly
selective expression of FOXP3 in thymus-derived Treg cells still remain to be
elucidated, we review here the current knowledge on the role of FOXP3 in the
development of Treg cells and the direct and indirect consequences of FOXP3
mutations on multiple arms of the immune response. Finally, we summarize the
newly acquired knowledge on the epigenetic regulation of FOXP3, still largely
undefined in human cells.
PMID- 24354326
TI - Chemical composition of volatiles from Opuntia littoralis, Opuntia ficus-indica,
and Opuntia prolifera growing on Catalina Island, California.
AB - The essential oils from the cladodes of Opuntia littoralis, Opuntia ficus-indica
and Opuntia prolifera growing wild on Santa Catalina Island, California, were
obtained by hydrodistillation and analysed by gas chromatography-mass
spectrometry (GC-MS). Terpenoids were the dominant class of volatiles in O.
littoralis, with the two main components being the furanoid forms of cis-linalool
oxide (10.8%) and trans-linalool oxide (8.8%). Fatty acid-derived compounds
dominated the essential oil of O. ficus-indica with linoleic acid (22.3%),
palmitic acid (12.7%), lauric acid (10.5%) and myristic acid (4.2%) as major
fatty acids. O. prolifera oil was composed of 46.6% alkanes and the primary
hydrocarbon component was heptadecane (19.2%). Sixteen compounds were common to
all the three Opuntia species.
PMID- 24354327
TI - Introduction of innovations in clinical practice with older adults.
PMID- 24354328
TI - The role of the occupational therapist in the management of neuropsychiatric
symptoms of dementia in clinical settings.
AB - Neuropsychiatric symptoms (NPS) of dementia include aggression, agitation,
depression, anxiety, delusions, hallucinations, apathy, and disinhibition. NPS
affect dementia patients nearly universally across dementia stages and
etiologies. They are associated with poor patient and caregiver outcomes,
including increased health care utilization, excess morbidity and mortality, and
earlier nursing home placement, as well as caregiver stress, depression and
reduced employment. There are no FDA-approved medications for NPS, but it is a
common clinical practice to use psychotropic medications such as antipsychotics,
to control symptoms; however, antipsychotics show only modest efficacy in
improving NPS and have significant risks for patients, including side effects and
mortality. Nonpharmacologic treatments are considered first-line by multiple
medical bodies and expert consensus, as they show evidence for efficacy and have
limited potential for adverse effects. Ideally, nonpharmacological management of
NPS in clinical settings occurs in multidisciplinary teams, where occupational
therapists play an important collaborative role in the care of the person with
dementia. Our group has articulated an evidence-informed structured approach to
the management of NPS that can be integrated into diverse practice settings and
used by providers of various disciplines. The "DICE" (Describe, Investigate,
Create, and Evaluate) approach is inherently patient- and caregiver-centered, as
patient and caregiver concerns are integral to each step of the process. DICE
offers a clinical reasoning approach through which providers can more efficiently
and effectively choose optimal treatment plans. The purpose of this paper is to
describe the role of the occupational therapy in using the DICE approach for NPS
management.
PMID- 24354329
TI - Utilizing technology to improve older adult health.
AB - Health care costs in the USA have been increasing, with the largest percentage of
revenues accruing to hospitals, health care professionals, and the pharmaceutical
industry. Increases are likely associated with increases in care costs for
chronic conditions, attributable in part to the aging of the population.
Technology in the form of telehealth is one important tool to improve the
efficiency of health care delivery. However, complex telehealth systems,
particularly those relying on remote detection of health status, can also
introduce challenges for management, due to system unreliability and particularly
the cost of false alarms. A case study is used to illustrate these phenomena.
PMID- 24354330
TI - Contemporary psychological approaches to life at the end of life.
AB - When people have a serious life-limiting illness, physical symptoms are often
prominent, both in the experience of the illness and in its treatment. No less
important, however, are psychological symptoms. A holistic, bio-psycho-social
spiritual approach to quality of life near the end of life must address
psychological distress of all types, including frank psychopathology, more
moderate problems with living, and existential distress. Responding to mental
health issues at the end of life requires (1) systematic and careful assessment,
and (2) deployment of evidence-based treatments. In recent years, standardized
assessment tools have been adapted or developed for use with people who have
serious illness, and the same has happened with psychological treatments.
Practitioners have several resources available to them. Given their practice
orientation centered on meaningful engagement, occupational therapists can play
an important role in responding to mental distress in patients with serious
illness whose lives are becoming more circumscribed because of their medical
condition or because of the mental distress itself. High-quality end-of-life care
depends on scrupulous attention to the full spectrum of thoughts, feelings, and
behaviors that unfold as death draws near.
PMID- 24354331
TI - Sexuality and physical intimacy in long-term care.
AB - Sexuality and sexual needs in older adults remains a neglected area of clinical
intervention, particularly so in long-term care settings. Because older adults in
medical rehabilitation and long-term care beds present with significant
frailties, and often significant neurocognitive disorders, it makes it difficult
for occupational therapists and other staff to evaluate the capacity of an older
adult resident to participate in sexual relationships. The current paper reviews
the current literature on sexuality and aging, examines some of the clinical
practices and guidelines regarding sexual expression in long-term care, and
presents two case examples. A semistructured interview and decision tree is
presented to assist therapists in making careful and informed decisions and
thereby balancing the needs for protection with the needs for autonomy.
PMID- 24354332
TI - Facilitating ADLs by caregivers of persons with dementia: the C3P model.
AB - The purpose of this paper is to explicate a change model for caregivers of
persons with dementia to assist them in facilitating meals in the home, at
community-based programs and in institutional settings. Building on a Social
Ecological Model, the C3P Model-Change the Person, Change the People, Change the
Place offers a clear method to adapt care strategies to foster independence while
providing appropriate support as the person with dementia cognitively and
functionally declines. Meals are highly embedded within a culture and are
ritualized events within a family requiring an individualized approach when
modifications are needed.
PMID- 24354333
TI - Driving with dementia: evaluation, referral, and resources.
AB - Driving is a highly valued instrumental activity of daily living, especially for
the older adults who consider it part of their definition of independence and
mobility. This paper discusses the issues associated with driving and older
adults, including the difficulty of identifying when it is time to give up the
keys. With a review of the latest research and need for specialized services for
those with diminished capacity, the paper highlights how general practice
occupational therapists must work in conjunction with driver rehabilitations
specialists to meet the need of this growing population. A framework for referral
and judgment is described and resources offered to practitioners to use.
PMID- 24354334
TI - Photoinduced demulsification of emulsions using a photoresponsive gemini
surfactant.
AB - This Article reports on the influence of light irradiation on the stability of
emulsions prepared using a photoresponsive gemini surfactant (C7-azo-C7) having
an azobenzene skeleton as a spacer. When mixtures of trans C7-azo-C7 aqueous
solution and n-octane are homogenized, stable emulsions are obtained in a
specific region of weight fraction and surfactant concentration. Fluorescence
microscopy observations using a small amount of fluorescent probes show that the
stable emulsions are oil-in-water (O/W)-type. UV irradiation of stable O/W
emulsions promotes the cis isomerization of trans C7-azo-C7 and leads to the
coalescence of the oil (octane) droplets in the emulsions, that is,
demulsification. While the equilibrated interfacial tension (IFT) between aqueous
trans C7-azo-C7 solution and octane is almost the same as that between aqueous
cis C7-azo-C7 and octane, the occupied area per molecule for C7-azo-C7 at
octane/water interface decreases with the cis photoisomerization of trans isomer.
Dynamic IFT measurement shows that UV irradiation to the interface between
aqueous trans C7-azo-C7 solution and octane brings about an increase in the
interfacial tension, indicating that the Gibbs free energy at the interface
increases. From these results, the cis isomerization of trans C7-azo-C7 molecules
at the O/W interface due to UV irradiation leads to direct contact between the
water and octane phases, because of the reduction of molecular area at the
interface, and subsequently makes the emulsions demulsified.
PMID- 24354335
TI - Cervical ripening with Foley catheter for induction of labor after cesarean
section: a cohort study.
AB - OBJECTIVE: To evaluate spontaneous vaginal delivery and complication rates after
induction of labor with a transcervical Foley catheter in women with a previous
cesarean delivery. DESIGN: Retrospective cohort study. SETTING: Secondary
teaching hospital in the second largest city of the Netherlands. POPULATION:
Women with a history of cesarean delivery (n = 208), undergoing induction of
labor with a Foley catheter in a subsequent pregnancy. MATERIAL AND METHODS: The
women who had induction of labor with a transcervical Foley catheter in the
Ikazia Hospital, Rotterdam, between January 2003 and January 2012, were
identified in a computerized database. Patient's records were checked for
accuracy. MAIN OUTCOME MEASURES: Vaginal delivery rate, cesarean section rate,
uterine rupture and maternal and neonatal (infectious) morbidity. RESULTS: Of the
women 60% had a spontaneous vaginal delivery and 11% were delivered by vacuum
extraction. Uterine rupture occurred in one woman. Postpartum hemorrhage was the
most common maternal complication (12%). Maternal intrapartum and postpartum
infections occurred in 5% and 1%. Proven neonatal infection was found in 3% of
the cases. Two perinatal deaths occurred (1%), of which one was related to
uterine rupture. CONCLUSION: Induction of labor with a transcervical Foley
catheter is an effective method to achieve vaginal delivery in women with a
previous cesarean delivery. There is a low risk of uterine rupture and maternal
and neonatal (infectious) morbidity in this cohort.
PMID- 24354336
TI - Light-induced opening and closing of the intramolecular hydrogen bond in
glyoxylic acid.
AB - The isomerization process of glyoxylic acid (GA) conformers and their complexes
with a water molecule were studied in a low temperature argon matrix. The
research target was to understand how starting conformation and complexation
affects the near-IR (NIR) induced conformer interconversion. The most stable GA
conformer (Tc) is characterized by an intramolecular hydrogen bond, and it is
found to undergo light-induced conformer interconversion slower than the open
(Tt) conformer. Upon complexation with water, the isomerization processes slow
down in the case of the Tc conformer, whereas for the Tt-based complex the
influence of water is negligible on the isomerization process.
PMID- 24354337
TI - Absorption, metabolism, and effects at transcriptome level of a standardized
French oak wood extract, Robuvit, in healthy volunteers: pilot study.
AB - The consumption of wine and spirits, traditionally aged in oak barrels, exposes
humans to roburin ingestion. These molecules belong to a class of ellagitannins
(ETs), and their only known source is oak wood. Very little is currently known
about roburin bioavailability and biological activity. We reported for the first
time human absorption of roburins from a French oak wood (Quercus robur) water
extract (Robuvit) by measuring the increase of total phenols (from 0.63 +/- 0.06
to 1.26 +/- 0.18 MUg GAE equiv/mL plasma) and the appearance of roburin
metabolites (three different glucoronidate urolithins and ellagic acid), in
plasma, after 5 days of supplementation. Robuvit supplementation induced also the
increase of plasma antioxidant capacity from 1.8 +/- 0.05 to 1.9 +/- 0.01 nmol
Trolox equiv/mL plasma. Moreover, utilizing a combined ex vivo cell culture
approach, we assessed the effect of Q. robur metabolites (present in human serum
after supplementation) on gene expression modulation, utilizing an Affymetrix
array matrix, in endothelial, neuronal, and keratinocyte cell lines. The
functional analysis reveals that Robuvit metabolites affect ribosome, cell cycle,
and spliceosome pathways.
PMID- 24354338
TI - The effects of a mineral trioxide aggregate-based sealer on the production of
reactive oxygen species, nitrogen species and cytokines by two macrophage
subtypes.
AB - AIM: To test the effects of a mineral trioxide aggregate-based sealer (MTA
Fillapex((r))) and MTA (MTA-Angelus((r))) on viability and on the production of
cytokines, reactive oxygen species (ROS) and nitrogen species (NO) by M1 and M2
inflammatory macrophages. METHODOLOGY: M1 (from C57BL/6 mice) and M2 (from BALB/c
mice) peritoneal inflammatory macrophages were obtained and cultured in vitro in
the presence of original and diluted extracts of MTA and MTA Fillapex (FLPX). The
cell viability, ROS release and the release of tumour necrosis factor-a,
interleukin (IL)-12, IL-10 and NO in response to stimulation with interferon
gamma and Fusobacterium nucleatum or Peptostreptococcus anaerobius were
evaluated. The data were analysed using the Mann-Whitney test and Student's t
test. RESULTS: Fillapex was cytotoxic at the highest concentrations (1:1;1:2) and
decreased the viability (P < 0.05) of both macrophage types (<20%). MTA did not
interfere with cellular viability. FLPX inhibited the release of ROS and
decreased NO release in F. nucleatum and P. anaerobius -stimulated M1 and M2
macrophages (<=25 MU mol L(-1)). F. nucleatum-stimulated M2 macrophage cultures
released lower levels of TNF-alpha when FLPX was added (<=1 ng mL(-1)). M2
macrophages released higher (>5 ng mL(-1)) levels of IL-10 than M1 macrophages.
Only M1 macrophage cultures produced IL-12p70. CONCLUSIONS: Fillapex impaired
effector immune responses during inflammation (M1 macrophages), as well as during
healing (M2 macrophages) responses.
PMID- 24354340
TI - Talk with Tiff: teen's inquiries to a sexual health website.
AB - Because of its availability, anonymity, and low cost of access, the Internet is
an increasingly common way for adolescents to find information about sensitive
issues. Sexual health website question portals are an important way for
adolescents to seek personalized information tailored to their individualized
needs. Few studies have examined the content within anonymous e-mails sent to
these question portals. The purpose of this qualitative evaluation was to analyze
thematic content of anonymous e-mails sent through a question portal on a
comprehensive sexual health clinic website for an adolescent family planning
clinic in a large city in the southwest United States. Between August 2009 and
June 2012, the e-mail server received questions from 484 individuals who were
seeking sexual health-related information. The authors used a content analysis to
identify recurrent themes in the questions submitted. The most common questions
regarded the cost of the clinic's services and testing for sexually transmitted
diseases. The questions revealed that adolescents lack basic sexual health
knowledge and hold many misconceptions. The findings support the usefulness of
online question portals as effective venues for teenagers to quickly and
anonymously obtain accurate information on sensitive issues.
PMID- 24354339
TI - Multi-organ injuries caused by lipopolysaccharide-induced periodontal
inflammation in rats: role of melatonin.
AB - BACKGROUND AND OBJECTIVE: Periodontitis, a chronic inflammatory disease caused by
oral bacterial infection, is considered to be a risk factor for systemic diseases
including diabetes mellitus, bacterial pneumonia, hyperlipidemia and
atherosclerosis. The aim of this study was to evaluate the effectiveness of
melatonin against periodontal inflammation-induced multiple organ injury in rats.
MATERIAL AND METHODS: Eighteen female Wistar albino rats were randomly divided
into three groups of six rats each: control; lipopolysaccharide (LPS); and LPS +
melatonin. During the experimental period (10 d) all rats in the LPS and LPS +
melatonin groups were given 10 MUL of LPS (from a 10 mg/mL standard solution of
LPS dissolved in saline) on days 1, 3 and 5. The rats in the LPS + melatonin
group were given 50 mg/kg of melatonin, daily for 10 d, starting on day 1 after
the administration of LPS. All rats were killed at the end of the experimental
period. Liver, kidney and lung tissues were removed for investigation by light
microscopy. RESULTS: The levels of serum aspartate aminotransferase (AST),
alanine transaminase (ALT) and blood urea nitrogen (BUN) were significantly
increased in the LPS group compared with the LPS + melatonin group (p < 0.05).
There was no significant change in the serum creatinine levels in the groups.
However, the changes in serum AST, ALT and BUN levels in the experimental groups
did not correlate with changes in histological data. Both LPS and LPS + melatonin
groups displayed structural features similar to those of the control group.
CONCLUSION: The results revealed that increased serum AST, ALT and BUN levels
following periodontitis are ameliorated with melatonin treatment.
PMID- 24354341
TI - Switching the BZ reaction with a strong-acid-free gel.
AB - In the present study, a novel gel with a semi-interpenetrating polymer network
(semi-IPN) that undergo the Belousov-Zhabotinsky (BZ) reaction without the
addition of a strong acid (HNO3 or H2SO4) was developed. The required
concentrations of the BZ substrates, sodium bromate (NaBrO3) and malonic acid
(MA), under these conditions were higher than under the normal BZ reaction
conditions, involving the addition of a strong acid. The period of the BZ
reaction with the novel gel (semi-IPN BZ gel) decreased with increasing
concentrations of NaBrO3 and MA. Moreover, the connection of the semi-IPN BZ gel
to a conventional BZ gel facilitated the reaction in the latter through the
propagation of the intermediates from the former to the latter. The BZ reaction
stopped when the conventional BZ gel was disconnected from the semi-IPN BZ gel.
These results demonstrate that the BZ reaction in the conventional BZ gel
underwent on-off switching, controlled by its attachment to the semi-IPN BZ gel.
This on-off switching mechanism would be valuable in controlling actuators and
robots without strong acids.
PMID- 24354342
TI - Mechanotransduction: forces, sensors, and redox signaling.
AB - Mechanotransduction describes the molecular mechanisms by which cells response to
changes in their physical environment by translating mechanical stimuli into
biochemical signals. It is now clear that reactive oxygen species (ROS) and redox
signaling play a crucial role in mechanotransduction analogous to their role in
chemotransduction. This Forum has particular emphasis on ROS generation with
altered mechanical stress, the upstream signal transduction pathways that
initiate ROS production, and the downstream effectors that lead to physiological
responses. There is particular emphasis on the role of ion channels in the
initial response and the role of NADPH oxidases as the major source of ROS. The
latter enzyme serves as the fulcrum of the mechanotransduction cascade. Although
it seems likely that all cells are mechanosensitive to some degree, we have
highlighted the responses of unicellular organisms (bacteria), bone cells, and
particularly cells of the vasculature (endothelial cells and vascular smooth
muscle cells). These cell types have been useful for studying the responses to
altered osmotic pressure, hemodynamic pressure, shear stress, and compressive
forces while exploring the link between signal transduction and
physiological/pathophysiological responses.
PMID- 24354343
TI - Two new flavanonols from the bark of Akschindlium godefroyanum.
AB - The first phytochemical investigation of the bark of Akschindlium godefroyanum
(Kuntze) H. Ohashi (Fabaceae), a Thai herbal medicine, resulted in the isolation
of two new flavanonols, 7,3',5'-trihydroxy-5-methoxyflavanonol (1) and 7,4'
dihydroxy-5,3'-dimethoxyflavanonol (2), and eight known compounds comprising one
flavonol, geraldol (3); three flavanonols, (+)-taxifolin (4), (+)-fustin (5) and
aromadendrin 5-methyl ether (6); one catechin, (-)-epigallocatechin (7); one
triterpenoid, lupeol (8); one steroid, stigmasterol (9) and one steroid
glycoside, stigmasterol-3-O-beta-d-glucoside (10). Their structures were
identified by spectroscopic methods.
PMID- 24354344
TI - Target attainment through algorithm design during intravenous insulin infusion.
AB - BACKGROUND: Algorithms were designed under a single model, to attain differing
designated glycemic targets during intravenous insulin infusion, and evaluated in
order to justify computerization of the model. The approximate maintenance rate
(MR) of insulin infusion is discovered according to rate of change of blood
glucose (BG) and previous insulin infusion rate (IR). During treatment, re
assignment of IR depends on MR and BG. For each MR, a roughly sigmoidal
relationship between BG and IR is specified, such that the inflection point falls
approximately at a true target BG. MATERIALS AND METHODS: Performance at St.
Francis Hospital, Evanston, IL, was examined during use of tabular algorithms
targeting three distinct BG ranges, appropriate for the treatment of
hyperglycemic hyperosmolar state, diabetic ketoacidosis, or hyperglycemia
accompanying other critical illness. Group membership was defined according to
algorithm used for patient treatment during the first 6 months of 2012. The group
geometric mean (GGM) and multiplicative surrogate standard deviation (MSSD) are
reported as group measures, respectively typifying the central tendency and
variability of individual patient BG distributions. RESULTS: Between first
attainment of target range BG control and a data collection end point, BG data
were evaluable during treatment courses for 58 patients. During this time frame,
in the group treated with target 100-149 mg/dL, there were five episodes of BG
<70 mg/dL for each of five patients, with the lowest being 57 mg/dL. The GGM
(with multiplicative standard deviation) was 269.4 (//* 1.06) mg/dL for the
algorithm having target 200-299 mg/dL (n = 3 treatment courses), 172.6 (//* 1.15)
mg/dL for target 150-199 mg/dL (n = 7), and 131.3 (//* 1.19) mg/dL for target 100
149 mg/dL (n = 48). The values of MSSD for the three groups were (//* 1.14), (//*
1.20), and (//* 1.20), respectively. CONCLUSIONS: The pilot series suggests that
once target range BG is attained, maintenance of control within each of three
distinct BG target ranges is achievable, according to choice of algorithm.
PMID- 24354345
TI - Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine
rich repeat kinase 2 (LRRK2) small molecule inhibitors.
AB - Leucine-rich repeat kinase 2 (LRRK2) has drawn significant interest in the
neuroscience research community because it is one of the most compelling targets
for a potential disease-modifying Parkinson's disease therapy. Herein, we
disclose structurally diverse small molecule inhibitors suitable for assessing
the implications of sustained in vivo LRRK2 inhibition. Using previously reported
aminopyrazole 2 as a lead molecule, we were able to engineer structural
modifications in the solvent-exposed region of the ATP-binding site that
significantly improve human hepatocyte stability, rat free brain exposure, and
CYP inhibition and induction liabilities. Disciplined application of established
optimal CNS design parameters culminated in the rapid identification of GNE-0877
(11) and GNE-9605 (20) as highly potent and selective LRRK2 inhibitors. The
demonstrated metabolic stability, brain penetration across multiple species, and
selectivity of these inhibitors support their use in preclinical efficacy and
safety studies.
PMID- 24354347
TI - Ocular coherence tomographic and clinical characteristics in patients of
punctuate inner choroidopathy associated with zonal outer retinopathy.
AB - PURPOSE: To describe the findings of optical coherence tomography and clinical
characteristics in patients of zonal outer retinopathy associated with punctuate
inner choroidopathy. METHOD: Review of consecutive cases on fundus photographs,
spectral domain ocular coherence tomography, fluorescein angiography, indocyanine
green angiography, visual field, and electrophysiological studies of patients
with punctate inner choroidopathy and associated zonal outer retinopathy.
RESULTS: This study involves 4 patients suffering visual field defect far beyond
the area corresponding to punctate inner choroidopathy lesions. Findings in
optical coherence tomography include attenuated signals of photoreceptor
inner/outer segment areas corresponding to visual field defect, and increased
choroidal thickness. After treatment with immunosuppressive agents, improvements
are noted in all 4 patients. CONCLUSION: Optical coherence tomography is helpful
in the diagnosis of patients suffering zonal ocular outer retinopathy associated
with punctate inner choroidopathy. All those patients responded well to
immunosuppressive agents.
PMID- 24354346
TI - The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation
have an impact on clinical outcome?
AB - CONTEXT: An activating mutation in the gene BRAF has been correlated with poorer
prognosis and more aggressive clinical course in papillary thyroid carcinoma
(PTC). We therefore hypothesized that the good prognosis, high 5-year disease
free rate and high survival rate of patients with less aggressive papillary
thyroid microcarcinoma (pT1aNo-x) would be associated with a lower incidence of
the BRAF(V600E) mutation. OBJECTIVES: To evaluate the frequency of the activating
mutation BRAF(V600E) in low-risk papillary thyroid microcarcinoma (pT1aNo-x at
the moment of diagnosis) and the association of the mutation with the clinical
outcome in a retrospective analysis. STUDY DESIGN: BRAF(V600E) was characterized
in 113 PTC patients diagnosed with pT1aNo-x (one PTC focus with a diameter <1 cm,
without lymph node or distant metastases according to IUCC/AJCC TNM staging
system 2010). Genotyping was performed on DNA extracted from thyroid tumour
tissue using direct capillary sequencing, and allele-specific amplification PCR
was used to resolve equivocal results. Retrospective analysis of the clinical
course of PTC was then correlated with BRAF status in the primary tumour tissue.
RESULTS: The BRAF(V600E) mutation was detected in 78 of the 113 pT1aNo-x patients
(69.0%). We observed no persistence, locoregional recurrence, lymph node or
distant metastases or deaths in the study group during the 12-year study (January
2001 to December 2012). CONCLUSIONS: The presence of the activating BRAF(V)
(600E) mutation in a significant percentage of papillary thyroid microcarcinoma
indicates that further analyses are required to verify its usefulness as a
predictor of clinical outcome in PTC. In this study, there was no correlation
between BRAF-positive primary focus of papillary microcarcinoma and more
aggressive or recurrent disease.
PMID- 24354348
TI - Feasibility of myocardial performance index for evaluation of left ventricular
function during dobutamine stress echocardiography before and after coronary
artery bypass grafting.
AB - AIMS: Myocardial performance index (MPI) is a measure of combined systolic and
diastolic myocardial function. In patients with coronary artery disease (CAD) an
increase in MPI is consistent with myocardial dysfunction. The objectives of this
study were to characterize the changes in MPI after coronary artery bypass graft
(CABG) at rest and at peak dobutamine stress echocardiography (DSE). METHODS AND
RESULTS: Thirty-six patients diagnosed with CAD and accepted for CABG were
studied by standard echocardiography and DSE 1 month prior and 3 month after
CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of
the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction
(EF; 42.7 +/- 8%) and wall-motion score index (WMSI; 1.1 +/- 0.2) were impaired
at rest as well as at peak DSE (EF; 49.2 +/- 9 and WMSI 1.4 +/- 0.2). MPI was
prolonged both at rest (0.61 +/- 0.13) and at peak DSE (0.78 +/- 0.16). After
CABG, EF and WMSI did not improve at rest (43.7 +/- 8% and 1.1 +/- 0.2,
respectively). On the other hand, MPI improved substantially both at rest (0.45
+/- 0.08; P < 0.001) and at peak DSE (0.56 +/- 0.1; P < 0.001). At peak DSE an
improvement of EF (54.2 +/- 9; P < 0.05) and WMSI (1.1 +/- 0.16; P < 0.001) was
seen as well. CONCLUSION: Myocardial performance index shows significant
improvement after CABG in patients with CAD both at rest and peak DSE and appears
to be a sensitive measure of myocardial function.
PMID- 24354350
TI - Vivien Thomas (1910-1985): the backstage pioneer and educator.
AB - Vivien Thomas (1910-1985) was an African-American scientist, pioneer, and
renowned educator. Thomas's contributions to cardiovascular surgery were
unequivocal, and yet it was only after his death that he gained more widespread
recognition. Thomas's more notable work involves aiding in the discovery of the
cause of traumatic shock, designing and guiding the first operation to treat
Tetralogy of Fallot, carrying out the first atrial septectomy, and helping
develop the electrical defibrillator. Thomas struggled amidst the adversities of
racism and the Great Depression (1929-1941), armed merely with a high school
degree. Nevertheless, his genius and determination eventually led him to receive
an honorary doctorate from John Hopkins University. His story inspired the
creation of the award winning PBS documentary in 2003 Partners of the Heart and
also the 2004 Emmy Award-winning HBO film Something the Lord Made. This article
will aim to provide an overview to the more notable events in Thomas's amazing
tale, with a particular focus on his work on the Tetralogy of Fallot.
PMID- 24354351
TI - A mathematical model of the colon crypt capturing compositional dynamic
interactions between cell types.
AB - Models of the development and early progression of colorectal cancer are based
upon understanding the cycle of stem cell turnover, proliferation,
differentiation and death. Existing crypt compartmental models feature a linear
pathway of cell types, with little regulatory mechanism. Previous work has shown
that there are perturbations in the enteroendocrine cell population of
macroscopically normal crypts, a compartment not included in existing models. We
show that existing models do not adequately recapitulate the dynamics of cell
fate pathways in the crypt. We report the progressive development, iterative
testing and fitting of a developed compartmental model with additional cell
types, and which includes feedback mechanisms and cross-regulatory mechanisms
between cell types. The fitting of the model to existing data sets suggests a
need to invoke cross-talk between cell types as a feature of colon crypt cycle
models.
PMID- 24354352
TI - Polyhedral oligomeric silsesquioxane-F68 hybrid vesicles for folate receptor
targeted anti-cancer drug delivery.
AB - Polyhedral Oligomeric Silsesquioxane (POSS)-F68 hybrid vesicles with an average
diameter of 700 nm are produced using a stable solution of heterofunctional POSS
having 3-aminopropyl and vinyl groups and pluronic F68 in ethanol-water mixture.
Thermogram and zeta potential values evidence the spontaneous self-assembly of
POSS into bilayers through H-bonding interaction between the aminopropyl groups,
and the effective stabilization of the POSS-bilayers by amphiphilic F68 during
solvent-evaporation to form the vesicles. The vesicles are noncytotoxic and
dispersible in aqueous solvents through steric stabilization provided by the
hydrophilic F68. A highly facile coinclusion method has been used for making
doxorubicin and folic acid loaded vesicles. Doxorubicin loaded in the vesicles
exhibits a controlled release profile in phosphate buffered saline. Confocal
microscopic and flow cytometric studies on the endocytosis of the vesicles by
HeLa and HOS cells prove that a noncovalent entrapment of excess folic acid in
the vesicles through H-bonding is sufficient to enhance the uptake significantly.
POSS-F68 vesicles in combination with folic acid and a chemotherapeutic can have
potential for targeted intracellular anti-cancer drug delivery.
PMID- 24354353
TI - Endoscopically proven case of rapid esophagogastric variceal progression and
rupture as a result of portal hypertension with liver sarcoidosis.
AB - Sarcoidosis is a multi-systemic disease of unknown etiology that results in the
development of non-caseating epithelioid granulomas. The liver is the third most
frequently involved organ after the lymph nodes and the lungs. Most cases of
liver sarcoidosis do not present with symptoms and involve minimal liver
dysfunction, but some cases display progression to portal hypertension and liver
cirrhosis, and finally to liver failure. The mechanism and the risk of
progression in liver sarcoidosis are still unknown because of the diagnostic
difficulty associated with this condition, and because follow-up examinations can
only be done in an invasive manner. Here, we present an informative case of liver
sarcoidosis with rapid progression of esophagogastric varices. Four months prior
to the definitive diagnosis, no signs of varices were observed on endoscopy, and
developmentof esophagogastric varices, rapid progression, and eventual rupture
occurred in a short period of time. A liver biopsy, carried out after endoscopic
sclerotherapy, revealed that granulomas primarily affected the portal area
without fibrotic and cirrhotic changes, which is considered a primary cause of
portal hypertension and esophagogastric varices. Following the liver biopsy, the
patient was given systemic steroids and is currently receiving outpatient care.
Thus, we should consider the possibility that liver sarcoidosis, even in the
absence of cirrhotic changes, can cause serious events such as esophagogastric
variceal rupture following rapid progression as a result of portal hypertension.
PMID- 24354354
TI - Workplace physical violence among hospital nurses and physicians in underserved
areas in Jordan.
AB - AIMS AND OBJECTIVES: To: (1) examine the incidence, frequency and contributing
factors to workplace violence among nurses and physicians in underserved areas in
Jordan, and (2) identify the existing policies and the management modalities to
tackle workplace violence. BACKGROUND: Workplace violence is a major problem in
healthcare organisations. An understanding of the nature of violence is essential
to implementing successful management. DESIGN: A descriptive exploratory research
design. METHODS: The questionnaire that was developed in 2003 by the
International Labor Office, the International Council of Nurses, the World Health
Organization, and the Public Services International was used to collect data from
a convenience sample of 521 Jordanian physicians and nurses (396 nurses, 125
physicians) who worked in hospitals located in underserved areas. RESULTS: Around
15% of the participants were exposed to physical violence. The factors that
contributed to workplace violence were related to absence of policies, inadequate
staffing and lack of communication skills. Only 16.9% of participants indicated
that there were specific policies available for dealing with physical workplace
violence. Strengthening security and providing training were some of the
important factors indicated by participants for decreasing violence in the
workplace. CONCLUSIONS: Workplace violence is a problem in underserved areas that
needs attention from administrators. Most participants were very dissatisfied
with the way the administrators dealt with the incidents. RELEVANCE TO CLINICAL
PRACTICE: Instituting firm policies against perpetrators and developing
protective violence guidelines to support healthcare staff in managing workplace
violence are paramount to tackle the problem of workplace violence.
PMID- 24354355
TI - Epidemiology of pemphigus vulgaris in the Northeast China: a 10-year
retrospective study.
AB - The aim of the present study was to evaluate the incidence, epidemiological,
clinical and therapeutic features of patients with pemphigus vulgaris in China.
We retrospectively investigated a total of 221 patients with pemphigus vulgaris.
The parameters including age at diagnosis/onset, sex, diagnostic methods,
hospitalizations, side-effects with different treatments, pemphigus vulgaris
associated diseases, the therapeutic features and duration of follow up were
evaluated. The male : female ratio was 1:1.40. The incidence rate was obviously
higher in two age groups, 31-40 years and 41-50 years. The mean age at onset was
44.19 +/- 21.45 years. The majority of patients (56.56%) presented the
mucocutaneous type. In addition, we found that various doses of corticosteroids
(including the mean initial dose, maximum control dose, total dose before
reducing and hospitalized total dose) exhibited statistical differences between
only corticosteroids and corticosteroids-immunosuppressant groups in mild,
moderate and severe pemphigus vulgaris (P < 0.05). Our survey suggested that
pemphigus vulgaris most frequently occurred in the 41-50-year age group in China
and the majority of patients manifested mucocutaneous lesions. Importantly, the
incidence rate in females was higher than in males. The patients who needed
combined immunosuppressant treatment, usually needed higher doses of
corticosteroids initially, to control the disease and over the total course of
treatment.
PMID- 24354356
TI - Time-resolved EPR study on the photoexcited triplet state of the electron-donor
acceptor complex formed in the system of fac-tris[2-(4-octyl-phenyl) pyridine]
iridium(III) and tetracene.
AB - The physical properties of the phosphorescent organic light-emitting diode
material fac-tris(phenylpyridine) iridium(III), Ir(ppy)3, have been reported with
experimental and theoretical studies. Here, the photochemical properties of the
excited triplet state of partially modified fac-tris[2-(4-octyl-phenyl) pyridine]
iridium(III), Ir(C8ppy)3, were investigated using time-resolved electron
paramagnetic resonance (tr-EPR) and optical methods by adding tetracene in the
toluene solution. The tr-EPR observation at 77 K revealed the following two
species: the excited triplet state of tetracene and another triplet species with
zero field splitting parameters of |D| = 0.088 cm(-1) and |E| = 0.018 cm(-1) with
characteristic spin polarization. The latter species was assigned to the electron
donor-acceptor (EDA) complex formed between Ir(C8ppy)3 and tetracene. The
mechanism of formation and the properties of this EDA complex, including the
information on the principal axes of (3)Ir(C8ppy)3*, are discussed.
PMID- 24354357
TI - Polymorphism of SLC25A32, the folate transporter gene, is associated with plasma
folate levels and bone fractures in Japanese postmenopausal women.
AB - AIM: Elevation of homocysteine is associated with an increased risk for bone
fractures. We previously reported that the methylenetetrahydrofolate reductase
(MTHFR) gene polymorphism is associated with homocysteine levels and fracture.
The association between the fracture and folate levels or their related gene
polymorphisms is not completely clear. We speculated that the SLC25A32 gene, the
mitochondrial inner membrane folate transporter, also could be implicated in the
regulation of folate metabolism and fracture. METHODS: A total of 851 Japanese
postmenopausal women participated in the association study between the single
nucleotide polymorphism genotype and plasma homocysteine or folate. We also
tested the association between the candidate single nucleotide polymorphism and
663 postmenopausal women. RESULTS: The AA genotype of rs2241777 single nucleotide
polymorphism at the 3'UTR region in the SLC25A32 gene was associated with lower
plasma folate concentration compared with the other genotypes in 851
postmenopausal women. A total of 674 postmenopausal ambulatory Japanese women
were followed up for 5.5 +/- 0.1 years (mean +/- SE). The AA genotype groups also
showed an apparently higher rate and earlier onset of incident fractures than the
other genotypes. A total of 407 participants had >70% young-adult mean bone
mineral density at the start of the observation. CONCLUSIONS: These results show
that the SLC25A32 gene polymorphism could be a risk factor for lower folate
concentration and future fracture.
PMID- 24354358
TI - Beneficial effect of betulinic acid on hyperglycemia via suppression of hepatic
glucose production.
AB - The inhibitory effect of betulinic acid (BA) on hepatic glucose production was
examined in HepG2 cells and high fat diet (HFD)-fed ICR mice. BA significantly
inhibited the hepatic glucose production (HGP) and gene expression levels of PGC
1alpha, PEPCK, and G6Pase. BA activated AMPK and suppressed the expression level
of phosphorylated CREB. These effects were all abolished in the presence of
compound C (an AMPK inhibitor). Moreover, inhibition of AMPK by overexpression of
dominant negative AMPK prevented BA from suppression of HGP, indicating that the
inhibitory effect of BA on HGP is AMPK-dependent. In addition, BA markedly
phosphorylated CAMKK, and phosphorylation of AMPK and ACC, and suppression of HGP
were all reversed in the presence of STO-609 (a CAMKK inhibitor), suggesting that
CAMKK is an upstream kinase for AMPK. In an animal study, HFD-fed ICR mice were
orally administered with 5 or 10 mg of BA per kg (B5 and B10) for three weeks.
Plasma glucose, triglyceride, and the insulin resistance index of the B10 group
were decreased by 34%, 59%, and 38%, respectively. In a pyruvate tolerance test,
pyruvate-induced glucose excursion was decreased by 27% when mice were pretreated
with 10 mg/kg of BA. In summary, BA effectively ameliorates hyperglycemia through
inhibition of hepatic gluconeogenesis via modulating the CAMKK-AMPK-CREB
signaling pathway.
PMID- 24354359
TI - Natural variant of the Helicobacter pylori CagA oncoprotein that lost the ability
to interact with PAR1.
AB - Helicobacter pylori strains carrying the cagA gene are associated with severe
disease outcomes, most notably gastric cancer. CagA protein is delivered into
gastric epithelial cells by a type IV secretion system. The translocated CagA
undergoes tyrosine phosphorylation at the C-terminal EPIYA motifs by host cell
kinases. Tyrosine-phosphorylated CagA acquires the ability to interact with and
activate SHP2, thereby activating mitogenic signaling and inducing cell
morphological transformation (hummingbird phenotype). CagA also interacts with
PAR1b via the CM sequence, resulting in induction of junctional and polarity
defects. Furthermore, CagA-PAR1b interaction stabilizes the CagA-SHP2 complex.
Because transgenic mice systemically expressing CagA develop gastrointestinal and
hematological malignancies, CagA is recognized as a bacterium-derived
oncoprotein. Interestingly, the C-terminal region of CagA displays a large
diversity among H. pylori strains, which influences the ability of CagA to bind
to SHP2 and PAR1b. In the present study, we investigated the biological activity
of v225d CagA, an Amerindian CagA of H. pylori isolated from a Venezuelan Piaroa
Amerindian subject, because the variant CagA does not possess a canonical CM
sequence. We found that v225d CagA interacts with SHP2 but not PAR1b.
Furthermore, SHP2-binding activity of v225d CagA was much lower than that of CagA
of H. pylori isolated from Western countries (Western CagA). v225d CagA also
displayed a reduced ability to induce the hummingbird phenotype than that of
Western CagA. Given that perturbation of PAR1b and SHP2 by CagA underlies the
oncogenic potential of CagA, the v225d strain is considered to be less oncogenic
than other well-studied cagA-positive H. pylori strains.
PMID- 24354360
TI - The relationship between beliefs about sleep and adherence to behavioral
treatment combined with meditation for insomnia.
AB - This study examined beliefs about sleep, as measured by the Dysfunctional Beliefs
and Attitudes about Sleep (DBAS) scale, as predictors of adherence to 3 specific
insomnia treatment recommendations: restriction of time spent in bed, maintenance
of a consistent rise time, and completion of daily meditation practice. Higher
DBAS scores predicted poorer adherence to restriction of time spent in bed and to
maintenance of a prescribed rise time. DBAS scores were not associated with
completion of daily meditation. These preliminary findings suggest that pre
treatment beliefs about sleep may impact patient engagement with behavioral
recommendations regarding time in bed and consistent rise time during treatment
for insomnia.
PMID- 24354361
TI - Ionizing radiation-induced responses: where free radical chemistry meets redox
biology and medicine.
AB - The biological effects of ionizing radiation (IR) from environmental, medical,
and man-made sources, as well as from space exploration are of broad health
concern. During the last 40 years it has become evident that, in addition to
short-lived free radical-mediated events initiated within microseconds of
exposure and generally thought to dissipate within milliseconds, IR-induced
production of reactive oxygen and nitrogen species as well as changes in redox
signaling linked to disruption of metabolic processes persist long after
radiation exposure. Furthermore, persistent IR-induced increases in the metabolic
production of reactive oxygen and nitrogen species appear to significantly
contribute to the delayed effects of IR exposure, including induction of adaptive
responses at low doses as well as carcinogenesis, fibrosis, inflammation, genomic
instability, and acceleration of the onset of degenerative tissue injury
processes associated with aging. The ability to identify the specific metabolic
mechanisms and dose-response relationships that contribute to adaptive responses
as well as persistent IR-induced injury processes holds great promise for
identifying novel strategies to mitigate the deleterious effects of IR exposure
as well as for gathering mechanistic information critical for risk assessment.
This Forum contains original and review articles authored by experts in the field
of radiobiology focusing on novel mechanisms involving redox biology and
metabolism that significantly contribute to the persistent biological effects
seen following IR exposure.
PMID- 24354362
TI - Age differences in sarcoidosis patients with posterior ocular lesions.
AB - PURPOSE: To determine if age- and gender-related differences are correlated with
the clinical aspects of posterior ocular lesions in sarcoidosis patients.
METHODS: Age at disease onset, gender, and ocular findings were obtained from
clinical records. Out of the 84 patients enrolled in the study, 22 were 45 years
old or younger while 62 were older than 45. After division of the fundus field
into three areas, lesion locations were investigated. RESULTS: The mean age of
disease onset in the male (44.5 +/- 16.8 years) was lower than in the female
(55.5 +/- 16.8 years). The lesions at the posterior segment in the older patients
were found to be located around the peripheral area. However, no statistically
significant difference in the location of the lesions was found for gender.
CONCLUSIONS: There was a statistically significant difference between younger and
older sarcoidosis patients for the disease lesions. Lesions were located around
the peripheral area at the posterior segment in older patients.
PMID- 24354363
TI - Preferential water exclusion in protein unfolding.
AB - Association of water with protein plays a central role in the latter's folding,
structure acquisition, ligand binding, catalytic reactivity, oligomerization, and
crystallization. Because these phenomena are also influenced by the net charge
content on the protein, the present study examines the association of water with
cytochrome c held at different pH values so as to allow its side chains to ionize
to variable extents. Equilibrium unfolding of differently charged cytochrome c
molecules in water-methanol binary mixtures, where the alcohol acts as the
cosolvent denaturant, was used to quantify the preferential exclusion of water
during the unfolding transition. The extent of exclusion was found to be related
to the net-charge-dependent molecular expansion of the protein in an alcohol-free
aqueous medium. The degree of water exclusion was also found to be linearly
related to the observed rate of protein unfolding, where the net charge contents
of the initial and final states are the same. The results suggest that side-chain
ionization, molecular expansion due to charge repulsion, and hence the loss of
tertiary contacts lead to additional water-protein association. Protein unfolding
rates appear to be linearly correlated with the effective number of water
molecules excluded across the end states of unfolding equilibria.
PMID- 24354365
TI - Revisiting basic nursing care.
PMID- 24354366
TI - Roadmap of miR-122-related clinical application from bench to bedside.
AB - INTRODUCTION: microRNA (miRNA) regulates target gene expression to influence many
physiological and pathophysiological processes. The liver-specific miRNA, miR
122, contributes to liver function and plays a very important role in hepatic
diseases including the viral hepatitis C (HCV). For this reason, developing an
miR-122-related clinical application could be very useful in managing or treating
many hepatic disorders. AREAS COVERED: This review introduces the basic concepts
of miRNA and miR-122. It also discusses the possibility of miR-122 as a biomarker
and summarizes the results of anti-miR-122 treatment from basic research to a
Phase IIa clinical trial. Furthermore, the authors discuss the potential
opportunities and challenges found in clinical trials with miravirsen. EXPERT
OPINION: miR-122 may be a useful biomarker as both a diagnostic and prognostic
tool. Furthermore, miravirsen is a novel treatment with great potential for
hepatic disease treatment, especially in HCV. However, there is certainly the
need for future investigations to better determine whether miR-122 is really
specific for liver. It is also important to elucidate whether miR-122 is actually
specific for HCV genome and further investigate the therapeutic potential of
miravirsen. Only once these studies have been completed can anti-miR-122
treatment potentially enter the clinical practice.
PMID- 24354367
TI - Science to Practice: can we diagnose nonalcoholic steatohepatitis with intravoxel
incoherent motion diffusion-weighted MR imaging?
AB - By showing that intravoxel incoherent motion parameters at diffusion-weighted
magnetic resonance (MR) imaging may be indicators of the microcirculatory changes
in patients with nonalcoholic steatohepatitis and fatty liver disease, Joo et al
have taken a step forward in the validation of quantitative MR imaging parameters
as biomarkers of nonalcoholic steatohepatitis and fatty liver disease. Further
steps, including standardization, validation, and multiparametric imaging, must
be taken before these parameters can be used as biomarkers in clinical practice.
PMID- 24354364
TI - delta-Thiolactones as prodrugs of thiol-based glutamate carboxypeptidase II
(GCPII) inhibitors.
AB - delta-Thiolactones derived from thiol-based glutamate carboxypeptidase II (GCPII)
inhibitors were evaluated as prodrugs. In rat liver microsomes, 2-(3
mercaptopropyl)pentanedioic acid (2-MPPA, 1) was gradually produced from 3-(2
oxotetrahydrothiopyran-3-yl)propionic acid (5), a thiolactone derived from 1.
Compound 1 was detected in plasma at concentrations well above its IC50 for GCPII
following oral administration of 5 in rats. Consistent with the oral plasma
pharmacokinetics, thiolactone 5 exhibited efficacy in a rat model of neuropathic
pain following oral administration.
PMID- 24354368
TI - Beyond the impact factor: enhancing the impact of imaging research published in
Radiology.
PMID- 24354372
TI - N. Reed Dunnick, MD, President, Radiological Society of North America, 2014.
PMID- 24354373
TI - How to perform parathyroid 4D CT: tips and traps for technique and
interpretation.
AB - Parathyroid four-dimensional (4D) computed tomography (CT) is an imaging
technique for preoperative localization of parathyroid adenomas that involves
multidetector CT image acquisition during two or more contrast enhancement
phases. Four-dimensional CT offers an alternative or additional tool in the
evaluation of primary hyperparathyroidism. The purpose of this article is to
describe the 4D CT technique and provide a practical guide to the radiologist for
imaging interpretation. The article will discuss the rationale for imaging,
approach to interpretation, imaging findings, and pitfalls.
PMID- 24354374
TI - Stress myocardial perfusion: imaging with multidetector CT.
AB - Computed tomographic (CT) coronary angiography is a well-established, noninvasive
imaging modality for detection of coronary stenosis, but it has limited accuracy
in demonstrating whether a coronary stenosis is hemodynamically significant. An
additional functional test is often required because both anatomic and functional
information is needed for guiding patient care. Recent developments in CT
technology allow CT evaluation of myocardial perfusion during vasodilator stress,
thereby providing information about myocardial ischemia. Investigators in several
single-center studies have established the feasibility of performing stress
myocardial perfusion CT imaging in small groups of patients and have shown that
stress myocardial perfusion CT in combination with CT coronary angiography
improved the diagnostic accuracy in comparison with CT coronary angiography
alone. However, CT perfusion acquisition protocols must be optimized in terms of
acquisition and reconstruction parameters, contrast material protocol injections,
and radiation dose. Further research is needed to establish the clinical
usefulness of this novel technique. The purpose of this review is to (a) provide
an overview of the physiology of coronary circulation and myocardial perfusion;
(b) describe the technical prerequisites, challenges, and mathematic modeling
related to CT perfusion imaging; (c) note recent advances in CT scanners and CT
perfusion protocols; and (d) discuss the interpretation of CT perfusion images.
Finally, a review and summary of the current literature are provided, and future
directions for research are discussed.
PMID- 24354377
TI - Addition of tomosynthesis to conventional digital mammography: effect on image
interpretation time of screening examinations.
AB - PURPOSE: To determine the effect of implementing a screening tomosynthesis
program on real-world clinical performance by quantifying differences between
interpretation times for conventional screening mammography and combined
tomosynthesis and mammography for multiple participating radiologists with a wide
range of experience in a large academic center. MATERIALS AND METHODS: In this
HIPAA-compliant, institutional review board-approved study, 10 radiologists
prospectively read images from screening digital mammography or screening
combined tomosynthesis and mammography examinations for 1-hour-long uninterrupted
sessions. Images from 3665 examinations (1502 combined and 2163 digital
mammography) from July 2012 to January 2013 were interpreted in at least five
sessions per radiologist per modality. The number of cases reported during each
session was recorded for each reader. The experience level for each radiologist
was also correlated to the average number of cases reported per hour. Analysis of
variance was used to assess the number of studies interpreted per hour. A linear
regression model was used to evaluate correlation between breast imaging
experience and time taken to interpret images from both modalities. RESULTS: The
mean number of studies interpreted in hour was 23.8 +/- 0.55 (standard deviation)
(range, 14.4-40.4) for combined tomosynthesis and mammography and 34.0 +/- 0.55
(range, 20.4-54.3) for digital mammography alone. A mean of 10.2 fewer studies
were interpreted per hour during combined tomosynthesis and mammography compared
with digital mammography sessions (P < .0001). The mean interpretation time was
2.8 minutes +/- 0.9 (range, 1.5-4.2 minutes) for combined tomosynthesis and
mammography and 1.9 minutes +/- 0.6 (range, 1.1-3.0) for digital mammography;
interpretation time with combined tomosynthesis and mammography was 0.9 minute
longer (47% longer) compared with digital mammography alone (P < .0001). With the
increase in years of breast imaging experience, the overall additional time
required to read images from combined tomosynthesis and mammography examinations
decreased (R(2) = 0.52, P = .03). CONCLUSION: Addition of tomosynthesis to
mammography results in increased time to interpret images from screening
examinations compared with time to interpret images from conventional digital
mammography alone.
PMID- 24354378
TI - Pancreatic ductal adenocarcinoma radiology reporting template: consensus
statement of the Society of Abdominal Radiology and the American Pancreatic
Association.
AB - Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high
mortality rate. Proper determination of the extent of disease on imaging studies
at the time of staging is one of the most important steps in optimal patient
management. Given the variability in expertise and definition of disease extent
among different practitioners as well as frequent lack of complete reporting of
pertinent imaging findings at radiologic examinations, adoption of a standardized
template for radiology reporting, using universally accepted and agreed on
terminology for solid pancreatic neoplasms, is needed. A consensus statement
describing a standardized reporting template authored by a multi-institutional
group of experts in pancreatic ductal adenocarcinoma that included radiologists,
gastroenterologists, and hepatopancreatobiliary surgeons was developed under the
joint sponsorship of the Society of Abdominal Radiologists and the American
Pancreatic Association. Adoption of this standardized imaging reporting template
should improve the decision-making process for the management of patients with
pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate
reporting of disease staging to optimize treatment recommendations that can be
offered to the patient. Standardization can also help to facilitate research and
clinical trial design by using appropriate and consistent staging by means of
resectability status, thus allowing for comparison of results among different
institutions.
PMID- 24354380
TI - Case 201: glomus tumor of the breast.
AB - History A 55-year-old woman presented to our breast clinic with 1-year history of
lancinating pain in the right breast that was exacerbated by blunt pressure and
cold temperature. She denied any family history of breast cancer or any personal
history of trauma, infection, or surgery of the breast. On clinical examination,
exquisite pain was generated by simple light pressure over the upper outer
quadrant of the right breast. Mammography and ultrasounography (US) with Doppler
analysis of the right breast were painful but were performed with the least
pressure possible.
PMID- 24354381
TI - Linear no-threshold model may not be appropriate for estimating cancer risk from
CT.
PMID- 24354382
TI - Optimization of thoracic US guidance for lung nodule biopsy.
PMID- 24354383
TI - Clarification of medical abbreviations, initialisms, and acronyms.
PMID- 24354384
TI - Screening for early detection of breast cancer: overdiagnosis versus public
education.
PMID- 24354385
TI - Is ground glass descriptive of a type of pulmonary nodule?
PMID- 24354386
TI - Diagnosis please case 196.
PMID- 24354389
TI - Central venous access via external jugular vein with CT-venography using a
multidetector helical 16-section CT.
AB - OBJECTIVE: To determine the success rate and complications of using the external
jugular vein (EJV) for central venous access with a preoperative estimate of the
detailed anatomical orientation of the cervical venous plexus using computed
tomography venography (CT-V). DESIGN: Prospective, observational human study.
SETTING: Surgical intensive care unit. PATIENTS: Fifty-two patients who were
undergoing EJV cannulations with CT-V using a Multidetector Helical 16-section CT
(MDCT). INTERVENTION: The preoperative anatomical estimation of the cervical
venous plexus was performed with CT-V using an MDCT. In particular, the
angulation between the EJV and the right subclavian vein (SCV) was measured. The
anatomical abnormalities and the angulation between the EJV and the anterior
jugular vein (AJV), transverse cervical vein (TCV), and suprascapular vein (SSV)
were estimated. MEASUREMENTS AND MAIN RESULTS: The success of CT-V was achieved
in 52 of 52 patients (100%). The mean angulation between the right EJV and the
right SCV was 144 +/- 36 degrees in the obtuse-angle cases (88%) and 72 +/- 28
degrees in the sharp-angle cases (12%). A plexus of veins under the clavicle was
most commonly responsible for insertion of the central venous catheter (CVC). The
EJV approach resulted in a 93% rate of successful cannulations. No complications
of pneumothorax or carotid artery puncture occurred during insertion procedures.
CONCLUSIONS: The EJV route is associated with comparable technical success and
lower major procedural complication. The EJV approach with CT-V guidance is an
option as the initial method when central venous cannulation must be performed
under suboptimal conditions.
PMID- 24354390
TI - On the role of specific interactions in the diffusion of nanoparticles in aqueous
polymer solutions.
AB - Understanding nanoparticle diffusion within non-Newtonian biological and
synthetic fluids is essential in designing novel formulations (e.g.,
nanomedicines for drug delivery, shampoos, lotions, coatings, paints, etc.), but
is presently poorly defined. This study reports the diffusion of thiolated and
PEGylated silica nanoparticles, characterized by small-angle neutron scattering,
in solutions of various water-soluble polymers such as poly(acrylic acid) (PAA),
poly(N-vinylpyrrolidone) (PVP), poly(ethylene oxide) (PEO), and
hydroxyethylcellulose (HEC) probed using NanoSight nanoparticle tracking
analysis. Results show that the diffusivity of nanoparticles is affected by their
dimensions, medium viscosity, and, in particular, the specific interactions
between nanoparticles and the macromolecules in solution; strong attractive
interactions such as hydrogen bonding hamper diffusion. The water-soluble
polymers retarded the diffusion of thiolated particles in the order PEO > PVP >
PAA > HEC whereas for PEGylated silica particles retardation followed the order
PAA > PVP = HEC > PEO. In the absence of specific interactions with the medium,
PEGylated nanoparticles exhibit enhanced mobility compared to their thiolated
counterparts despite some increase in their dimensions.
PMID- 24354391
TI - Validity of the Chinese version of the brief index of sexual functioning for
women with a new scoring algorithm and comparison of normative and recurrently
depressed Han Chinese population.
AB - INTRODUCTION: The Brief Index of Sexual Functioning for Women (BISF-W) is proved
to be a useful instrument to assess female sexual function, but the validation
information of its Chinese version is still unavailable. It has not been used to
assess female sexual function among Han Chinese women with recurrent depression.
AIM: This study aims to validate the Chinese version of BISF-W (C-BISF-W) with a
new scoring algorithm and evaluate the impact of recurrent depression on sexual
function among Han Chinese women. METHODS: Three groups of subjects, 63
unmedicated patients with recurrent depression, 50 medicated remitted patients
with recurrent depression, and 92 healthy controls were enrolled in this study.
Sexual function was assessed with C-BISF-W. A new scoring algorithm was developed
to provide an overall composite score (G) and seven dimension scores: desire
(D1), arousal (D2), frequency of sexual activity (D3), orgasm (D4), sexual
interaction (D5), relationship dissatisfaction (D6), and problems affecting
sexual function (D7). MAIN OUTCOME MEASURES: Psychometric analyses were
conducted. RESULTS: Four factors whose Eigenvalues were higher than 1 were
extracted, explaining 61.426% of the total variance. Compared with healthy age
matched control, unmedicated cases scored significantly lower in G, D1, D2, D3,
D4 and D5, whereas these were higher in D6 and D7. No significant difference was
found in the scores of G, D1, D2, D3, D4, and D5 between remitted cases and
control, but the former scored higher in D6 and D7 than the latter. In comparison
with unmedicated cases, medicated remitted cases got a higher score in G, D1, D2,
and D5. For the healthy control, sexual function (G) was negatively correlated
with age. CONCLUSIONS: With the new scoring algorithm, C-BISF-W is proved to be a
validated instrument to assess female sexual function. The impact of recurrent
depression on female sexual function is negatively profound and extensive.
PMID- 24354392
TI - Using terahertz spectroscopy and solid-state density functional theory to
characterize a new polymorph of 5-(4-pyridyl)tetrazole.
AB - A new high-temperature polymorph of 5-(4-pyridyl)tetrazole has been discovered
and characterized using X-ray crystallography and terahertz (THz) spectroscopy.
The THz spectrum of the new polymorph was compared to the previously published
form and was replicated by means of solid-state density functional theory.
Terahertz spectroscopy was used to determine the influence of the different
packing motifs on the molecular and low energy lattice vibrations displayed in
the region from 10 to 100 cm(-1). It was found that there is only a ~2 cm(-1)
difference in the primary peak location, caused by a whole molecule rotation
along the principal a axis, between the two polymorphic forms. In addition, the
energy of formation was determined, and it was found that the previously known
polymorphic form is more stable by ~0.25 kJ/mol, compared to the newly discovered
form.
PMID- 24354393
TI - Flower-like ZnO-Ag2O composites: precipitation synthesis and photocatalytic
activity.
AB - Ag2O-decorated flower-like ZnO composites were fabricated through a chemical
precipitation process. X-ray diffraction analysis confirms the co-existence of
cubic Ag2O and wurtzite ZnO phases. Scanning electron microscopy images reveal
Ag2O nanoparticles located on the rough surface of ZnO flowers. The
photocatalytic activities of the composites with various mole ratios were
evaluated by the degradation of methyl orange (MO) under ultraviolet irradiation,
which confirms that the composite shows superior activity to that of pure ZnO and
Ag2O. The improvement can be ascribed to the deposited Ag2O forming the p-n
junction at the interface of ZnO and Ag2O, resulting in the transfer of
photocarriers and suppressing the electron-hole recombination rate.
PMID- 24354394
TI - Identification, characterization, and quantification of an anti-pyridoxine factor
from flaxseed using ultrahigh-performance liquid chromatography-mass
spectrometry.
AB - In the present study, the anti-pyridoxine compounds linatine (1-[(n-gamma-L
glutamyl)amino]-D-proline) and 1-amino-D-proline (1ADP) were quantified following
extraction from defatted flaxseed using aqueous isopropanol as a solvent, with
extraction variables including time, temperature, and the solid/solvent ratio.
Both linatine and 1ADP were identified, characterized, and quantified via
UPLC/ESI-MS using authentic standards. To optimize the extraction conditions for
these anti-pyridoxine compounds, a response surface methodology was applied using
a second-order polynomial to describe the experimental data. The predicted model
for the optimal extraction was significant (P < 0.05) with a R(2) of 0.82. A
varietal analysis showed that the amount of anti-pyridoxine present in flaxseed
ranged from 177 to 437 MUg 1ADPE/g of whole seed. The current study establishes
the content of specific anti-pyridoxine factors in flaxseed and positions the
data for use in subsequent risk assessment modeling.
PMID- 24354397
TI - Concise and scalable synthesis of aspalathin, a powerful plasma sugar-lowering
natural product.
AB - Aspalathin (1), a dihydrochalcone C-glucoside, exhibits powerful plasma sugar
lowering properties and thus potentially could be used to treat diabetes. Small
quantities occur in rooibos tea, manufactured via fermentation of the leaves of
Aspalathus linearis, hence necessitating the need for an efficient and concise
synthesis. Efforts to synthesize aspalathin (1) via coupling of a glucose donor
to the nucleophilic phloroglucinol ring of the dihydrochalcone moiety have
invariably failed, presumably because of ring deactivation by the electron
withdrawing carbonyl group. Reduction of the carbonyl group of a chalcone (15)
and coupling of the resulting 1,3-diarylpropane (16) to tetra-O-benzyl-beta-D
glucopyranose afforded the C-glucosyl-1,3-diarylpropane (17). Regiospecific
benzylic oxidation regenerated the carbonyl group and afforded the per-O
methylaspalathin (1a) quantitatively. This method was not successful with the per
O-benzyl-protected dihydrochalcone. However, the nucleophilicity of the phenolic
hydroxy groups of the dihydrochalcone or its acetophenone precursor is not
diminished by the carbonyl group. Thus, glucosylation of the di-O
benzylacetophenone (5c) at -40 degrees C afforded the alpha-O-glucoside (19) in
86% yield. Raising the temperature allowed facile BF3-catalyzed rearrangement to
the beta-C-glucoside (6b), which upon hydrogenation, afforded aspalathin (1) in
80% overall yield [based on the usage of di-O-benzylphloroacetophenone (5c) and
tetra-O-benzyl-1alpha-fluoro-beta-D-glucose (2e)].
PMID- 24354396
TI - Leptin modulates electrophysiological characteristics and isoproterenol-induced
arrhythmogenesis in atrial myocytes.
AB - BACKGROUND: Obesity is an important risk factor for atrial fibrillation (AF).
Leptin is an important adipokine. However, it is not clear whether leptin
directly modulates the electrophysiological characteristics of atrial myocytes.
RESULTS: Whole cell patch clamp and indo-1 fluorescence were used to record the
action potentials (APs) and ionic currents in isolated rabbit left atrial (LA)
myocytes incubated with and without (control) leptin (100 nM) for 1 h to
investigate the role of leptin on atrial electrophysiology. Leptin-treated LA
myocytes (n = 19) had longer 20% of AP duration (28 +/- 3 vs. 21 +/- 2 ms, p <
0.05), but similar 50% of AP duration (51 +/- 4 vs. 50 +/- 3 ms, p > 0.05), and
90% of AP duration (89 +/- 5 vs. 94 +/- 4 ms, p > 0.05), as compared to the
control (n = 22). In the presence of isoproterenol (10 nM), leptin-treated LA
myocytes (n = 21) showed a lower incidence (19% vs. 54.2%, p < 0.05) of delayed
afterdepolarization (DAD) than the control (n = 24). Leptin-treated LA myocytes
showed a larger sodium current, but a smaller ultra-rapid delayed rectifier
potassium current, and sodium-calcium exchanger current than the control. Leptin
treated and control LA myocytes exhibited a similar late sodium current, inward
rectifier potassium current, transient outward current and L-type calcium
current. In addition, the leptin-treated LA myocytes (n = 38) exhibited a smaller
intracellular Ca2+ transient (0.21 +/- 0.01 vs. 0.26 +/- 0.01 R410/485, p < 0.05)
and sarcoplasmic reticulum Ca2+ content (0.35 +/- 0.02 vs. 0.43 +/- 0.03
R410/485, p < 0.05) than the control LA myocytes (n = 42). CONCLUSIONS: Leptin
regulates the LA electrophysiological characteristics and attenuates
isoproterenol-induced arrhythmogenesis.
PMID- 24354395
TI - Association between shift work and obesity among female nurses: Korean Nurses'
Survey.
AB - BACKGROUND: Shift work has been hypothesized as a risk factor for obesity. In
this study, we investigated the association between current shift work and body
mass index (BMI) among female nurses in Korea. The relationship between duration
of shift work and BMI of the participants was also evaluated. METHODS: This cross
sectional survey evaluated participants in the Korean Nurses' Survey, conducted
from October to December 2011, using web-based self-administered questionnaires.
A total of 9,989 nurses were included among 10,000 who registered on the survey
web site (5,287 shift workers and 4,702 non-shift workers). Current shift workers
were divided into tertiles of shift work duration (0.08-3.00 years, n = 1,732;
3.08-6.75 years, n = 1,731; and 6.83-38.00 years, n = 1,686). The BMI thresholds
of overweight and obesity were >=23 kg/m2 and >=25 kg/m2, respectively. Data were
analyzed using SPSS software. RESULTS: Mean participant age was 33.2 +/- 8.6
years and the mean BMI was 20.9 +/- 2.5 kg/m2. There were statistically
significant differences in current smoking status, regular drinking habit,
dietary habits, regular exercise, sleep problems and self-perceived health status
according to duration of shift work. The overall prevalence of overweight/obesity
(18.6%) and obesity (7.4%) increased significantly as shift work duration
increased from the lowest to highest tertile (P for trend <0.001). Multivariate
logistic regression analysis revealed no association between current shift work
and BMI. However, after adjusting for potential confounders, the participants
with the longest duration of shift work were 1.63 (95% CI, 1.22-2.17) times more
likely to be overweight or obese than those with the shortest duration. There was
a significant positive association between obesity and shift work duration in the
unadjusted analysis; however, it was attenuated and no longer significant in the
multivariate model. CONCLUSIONS: The duration of shift work was positively
associated with prevalence of overweight/obesity in nurses in Korea. Although
these findings need to be confirmed in prospective studies, they suggest that
special attention should be paid to female nurses with a long duration of shift
work.
PMID- 24354398
TI - Nurses' knowledge of evidence-based guidelines on the prevention of peripheral
venous catheter-related infections: a multicentre survey.
AB - AIMS AND OBJECTIVES: To evaluate nurses' knowledge of guidelines for preventing
infections associated with peripheral venous catheters. BACKGROUND: Guidelines
for the prevention of intravascular catheter-related infections are an important
tool to help healthcare professionals minimise the risk of infection. However,
they are not always applied by nurses. The literature on this topic is limited,
and no study examined this matter for peripheral venous catheters. DESIGN: This
cross-sectional study was carried out from November 2011-June 2012. METHODS: The
nurses' knowledge of peripheral venous catheter guidelines and its association
with gender, experience, education and the ward membership was assessed using a
validated questionnaire. RESULTS: Sixteen hospitals from six regions of Italy
participated, and 933 questionnaires were collected. Most participants were
female (70.1%), undergraduate (51.8%), worked in medical (35.8%) and surgical
departments (28.0%), and had >10 years of experience (55.0%). The median score on
10 questions was 6 of 10. A majority of nurses knew it is recommended to replace
peripheral venous catheters routinely (90.0%), to perform an aseptic technique
during connecting/disconnecting the infusive lines (55.2%), and to replace the
administration set <24 hour when lipid emulsions have been infused (88.4%). Of
note, 52.6% of nurses advocated the use of steel needles, a potentially dangerous
practice. In multivariate analysis, a higher level of education and the area of
work were associated with better test scores. CONCLUSION: The sample of nurses'
knowledge to some recommendations is frequently low. This could be a potential
risk factor for patient safety. The results should sensitise healthcare managers
to improve nursing training and education, according to clinical risk management
perspectives. RELEVANCE TO CLINICAL PRACTICE: These data request for more
emphasis on international guidelines in infection prevention initiatives.
PMID- 24354399
TI - Lesions along the upper motor neuronal pathway with locked-in features after
lightning strike and cardiac arrest: a case-review analysis.
AB - OBJECTIVE: This study describes a case of lesions of the upper motor neuronal
pathway with locked-in features after lightning strike and cardiac arrest.
DESIGN: A case-review analysis. METHODS: In a 29-year-old male who was hit by a
lightning strike during farming activities, cardiopulmonary resuscitation was
provided first by co-workers and continued with success by the medical rescue
service. After conducting advanced life support under monitoring and therapeutic
hypothermia, quadriplegia with facial diplegia was recognized. A review was
undertaken detailing the clinical course. RESULTS: MR imaging presented signs
consistent with hypoxia-induced damage and diffusion-weighted MR images revealed
pronounced damages along the upper motor neuronal pathway. A reactive
electroencephalogram pattern, sustained eye movement and the patient
communicating via eye-blinking were interpreted as locked-in features. Two weeks
after admission the patient was transferred to a neurological rehabilitation
centre for further professional care. CONCLUSION: Direct damage of the upper
motor neuron pathway due to the current of the lightning should be considered,
albeit the relative contribution of hypoxia-induced damage cannot be separated.
PMID- 24354400
TI - Delayed blood pressure recovery ratio and its relation to endothelial function
and left ventricular diastolic function in prediabetics.
AB - BACKGROUND: Endothelial function plays a key role in determining the clinical
manifestations of established atherosclerotic lesions and has shown to be
associated with suppressed sympathetic tone. Abnormal heart rate recovery (HRR)
and systolic blood pressure (SBP) response during recovery has been found to have
diagnostic role for detecting cardiovascular risk. AIM: To investigate whether
with abnormal HRR and delayed SBP recovery ratio after exercise could predict
endothelial dysfunction in prediabetic subjects. METHODS: Ninety-two prediabetic
patients underwent brachial artery flow-mediated dilatation (FMD) test and a
maximal exercise stress test. Seventy-eight healthy subjects served as a control
group. HRR at 1 minute (HRR1 ) and SBP recovery ratio (SBPRR3 ) was defined as
the SBP at minute 3 of recovery divided by SBP at peak exercise. Left ventricular
diastolic function was assessed utilizing both conventional and tissue Doppler
echocardiography. RESULTS: Flow-mediated dilatation was significantly decreased
in prediabetics versus controls (P < 0.0001). Isovolumetric relaxation time and
E/E' were significantly increased in prediabetics (P < 0.01 and <0.001). Delayed
SBPRR3 was significantly correlated with impaired endothelial function and (E/E')
in prediabetics (r = 0.62, P < 0.001 and r = 0.56, P < 0.001, respectively).
Stepwise linear regression analysis revealed that HRR1 and SBPRR3 were
significant predictors of endothelial dysfunction (r = 0.61, r(2) = 0.37, P <
0.01 and r = 0.51; r(2) = 27; P < 0.0001). CONCLUSIONS: Abnormal HRR1 and delayed
SBP response detected during recovery imply a significant correlation with
impaired endothelial function and diastolic dysfunction in prediabetics.
PMID- 24354401
TI - Clinical accuracy of two electronic apex locators in teeth with large periapical
lesions.
AB - AIM: To evaluate in vivo the accuracy of two electronic apex locators (EALs) in
determining the position of the apical foramen of teeth with large periapical
lesions and persistent intracanal exudate. METHODOLOGY: Thirty-three maxillary
anterior teeth assigned for periapical surgery were selected. Following the
preparation of standard endodontic access cavities, electronic working lengths
were determined using the ProPex and Apex Pointer apex locators. During
endodontic surgery, the actual root canal length of each tooth was measured by
positioning a K-file at the most coronal border of the major foramen. Root canal
treatments combined with apical surgery were then completed. Data were analysed
with paired t-tests. RESULTS: ProPex and Apex Pointer were accurate (within +/-
0.5 mm) 97% and 94% of the time. No significant differences were detected between
the apex locators (P = 0.325). CONCLUSIONS: Despite the presence of exudate in
the root canals, the position of the major foramen in teeth with large periapical
lesions can be determined with high level of precision either by ProPex or Apex
Pointer. Both EALs can be used safely in working length determination of teeth
with large periapical lesions, which have persistent intracanal exudate.
PMID- 24354402
TI - Conversion from irregular to regular wide QRS tachycardia: what is the mechanism?
PMID- 24354403
TI - Early onset bilateral anterior uveitis preceding a late manifestation of juvenile
idiopathic arthritis: a case report.
PMID- 24354404
TI - Propofol versus traditional sedative agents for advanced endoscopic procedures: a
meta-analysis.
AB - BACKGROUND AND AIM: The optimum method for sedation for advanced endoscopic
procedures is not known. Propofol deep sedation has a faster recovery time than
traditional sedative agents, but may be associated with increased complication
rates. The aim of the present study was to pool data from all available studies
to systematically compare the efficacy and safety of propofol with traditional
sedative agents for advanced endoscopic procedures. METHODS: Databases including
PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled
Trials updated as of January 2013 were searched. Main outcome measures were
procedure duration, recovery time, incidence of complications (hypotension,
hypoxia), sedation level, patient cooperation and amnesia during advanced
endoscopic procedures such as endoscopic retrograde cholangiopancreatography,
endoscopic ultrasonography, and deep small bowel enteroscopy. RESULTS: Nine
prospective randomized trials with a total of 969 patients (485 propofol, 484
conscious sedation) were included in the meta-analysis. Pooled mean difference in
procedure duration between propofol and traditional sedative agents was -2.3 min
[95% CI: -6.36 to 1.76, P = 0.27], showing no significant difference in procedure
duration between the two groups. Pooled mean difference in recovery time was
30.26 min [95% CI: -46.72 to -13.80, P < 0.01], showing significantly decreased
recovery time with propofol. There was also no significant difference between the
two groups with regard to hypoxia and hypotension. CONCLUSIONS: Propofol for
advanced endoscopic procedures is associated with shorter recovery time, better
sedation and amnesia level without an increased risk of cardiopulmonary
complications. Overall patient cooperation was also improved with propofol
sedation.
PMID- 24354405
TI - Laparoscopic sleeve gastrectomy: review of 500 cases in single surgeon Australian
practice.
AB - INTRODUCTION: Reported results and techniques of laparoscopic sleeve gastrectomy
(LSG) are variable. Our objective was to assess results of weight loss,
complications and reflux in a large consecutive series of LSG, describing
technical detail which contributed to outcomes. METHODS: Retrospective review of
prospectively collected data of 500 consecutive patients undergoing LSG. Patient
demographics, weight loss, complications and functional outcomes were analysed
and operative technique described. RESULTS: Five hundred patients underwent LSG
over 3 years (37 revisional). Mean (range) preoperative body mass index was 45
kg/m(2) (35-76 kg/m(2) ). Mean follow-up and length of hospital stay were 14
months (1-34) and 3.8 days (3-12), respectively. All-cause 30-day readmission
rate 1.2%. Mean excess weight loss (interquartile range, available patient data)
was 43% (22-65%, 423 patients), 58% (45-70%, 352 patients), 76% (52-84%, 258
patients), 71% (51-87%, 102 patients) and 73% (55-86%, 13 patients) at 3, 6, 12,
24, 36 months, respectively. There was no mortality. Intraoperative complications
occurred in two (0.4%) - splenic bleeding; bougie related oesophageal injury.
Early surgical complications in four (1.2%) patients (one staple line leak and
three post-operative bleeds). Other early complications occurred in three (0.6%)
patients (one pseudomembranous colitis; one central line sepsis; one portal
venous thrombosis) and late in four (0.8%) patients (three port-site incisional
hernias; mid-sleeve stricture requiring endoscopic dilatation). Gastro
oesophageal reflux symptoms decreased from 45 to 6%. CONCLUSION: With attention
to detail, LSG can lead to good excess weight loss with minimal complications.
Tenants to success include repair of hiatal laxity, generous width at angula
incisura and complete resection of posterior fundus.
PMID- 24354406
TI - Intergrowth and interfacial structure of biomimetic fluorapatite-gelatin
nanocomposite: a solid-state NMR study.
AB - The model system fluorapatite-gelatin allows mimicking the formation conditions
on a lower level of complexity compared to natural dental and bone tissues. Here,
we report on solid-state NMR investigations to examine the structure of
fluorapatite-gelatin nanocomposites on a molecular level with particular focus on
organic-inorganic interactions. Using (31)P, (19)F, and (1)H MAS NMR and
heteronuclear correlations, we found the nanocomposite to consist of crystalline
apatite-like regions (fluorapatite and hydroxyfluorapatite) in close contact with
a more dissolved (amorphous) layer containing first motifs of the apatite crystal
structure as well as the organic component. A scheme of the intergrowth region in
the fluorapatite-gelatin nanocomposite, where mineral domains interact with
organic matrix, is presented.
PMID- 24354407
TI - Berberine ameliorates experimental autoimmune neuritis by suppressing both
cellular and humoral immunity.
AB - Berberine (BBR), an isoquinoline derivative alkaloid, has been extensively used
in traditional Chinese medicine for the treatment of diarrhoea, rheumatic
diseases, diabetes, etc. Recent studies have demonstrated new biological
properties of BBR and suggested the possibility of BBR to be a therapeutic agent
for some autoimmune diseases. To explore the effect of BBR on the development of
experimental autoimmune neuritis (EAN), BBR was administered intragastrically
daily to Lewis rats immunized with P0 peptide 180-199 in Freund's complete
adjuvant. We found BBR treatment resulted in amelioration of EAN, accompanied by
suppressed lymphocyte (in particular CD4(+) T cell) proliferation, downregulated
Th1 (TNF-alpha) and Th2 (IL-10) cytokines and reduced anti-P0 peptide 180-199
IgG1 and IgG2a. In brief, BBR played a role in ameliorating EAN by suppressing
both cellular and humoral immunity. Thus, our study suggests that BBR may be a
potential therapeutic agent for the autoimmune disease in the peripheral nervous
system, such as Guillain-Barre syndrome.
PMID- 24354408
TI - Activation of alkynes with B(C6F5)3--boron allylation reagents derived from
propargyl esters.
AB - Novel allyl boron compounds are readily synthesized via rearrangement reactions
between Lewis acidic B(C6F5)3 and propargyl esters. These reactions proceed
through an initial cyclization followed by ring-opening and concurrent C6F5-group
migration. In the absence of disubstitution adjacent to the ester oxygen atom, an
allyl boron migration rearrangement leads to formal 1,3-carboboration products.
These allyl boron compounds act as allylation reagents with aldehydes introducing
both a C3-allyl fragment and a C6F5-unit as a single anti-diastereomer. In these
reactions, B(C6F5)3 activates the alkynes, prompting the rearrangement processes
and enabling installations of C6F5 and R-groups.
PMID- 24354409
TI - PbO-modified TiO2 thin films: a route to visible light photocatalysts.
AB - PbO clusters were deposited onto polycrystalline titanium dioxide (anatase) films
on glass substrates by aerosol-assisted chemical vapor deposition (AACVD). The as
deposited PbO/TiO2 films were then tested for visible light photocatalysis. This
was monitored by the photodegradation of stearic acid under visible light
conditions. PbO/TiO2 composite films were able to degrade stearic acid at a rate
of 2.28 * 10(15) molecules cm(-2) h(-1), which is 2 orders of magnitude greater
than what has previously been reported. The PbO/TiO2 composite film demonstrated
UVA degradation of resazurin redox dye, with the formal quantum yield (FQY) and
formal quantum efficiency (FQE) exceeding that of a TiO2 film grown under the
same conditions and Pilkington Activ, a commercially available self-cleaning
glass. This work correlates with computational studies that predicted PbO
nanoclusters on TiO2 form active visible light photocatalysts through new
electronic states through PbO/TiO2 interfacial bonds resulting in new electronic
states above the valence band maximum in TiO2, shifting the valence band upward
as well as more efficient electron/hole separation with hole localization on PbO
particles and electron on the TiO2 surface.
PMID- 24354410
TI - Temporal determination of lung NO system and COX-2 upregulation following
ischemia-reperfusion injury.
AB - BACKGROUND: Pulmonary ischemia-reperfusion (IR) is a biopathological event
detectable in several clinical conditions, including lung transplantation,
cardiopulmonary bypass, resuscitation, and pulmonary embolism. The understanding
behind the activation of various inflammatory mediators regulating the apoptotic
pathways remains largely unknown. We investigated the temporal expression of
endothelial nitric oxide (eNOS), inducible (iNOS), and cyclooxygenase-2 (COX-2)
proteins following lung-IR injury. METHODS: Lung IR was induced in anesthetized
rats. One hour ischemia was performed by clamping the left hilum. eNOS, iNOS, and
COX-2 levels in the bronchoalveolar lavage (BAL) were measured at different time
points after restoring lung perfusion in conjunction with histological changes
and cellular apoptosis. RESULTS: BAL-eNOS levels were increased as early as 3
hours post IR, attaining the highest values (5.5 U/mL) at 3 hours, compared to
non-IR values (2.8 U/mL). BAL-iNOS increased at 3-hour post-IR (3 U/mL). iNOS
reached the highest levels at 24 hours (4.5 U/mL) as compared to nonischemic
lungs (1.8 U/mL). COX-2 peaked at 12 hours (.025 U/mL) compared to 3, 24, and 48
hours. Highest apoptotic rates were detected at 12 and 48 hours following IR.
CONCLUSIONS: The time-associated involvement of eNOS, iNOS, and COX-2 enzymes
during the evolution of IR injury may point to an early reaction of the NOSs
system versus the COX-2. Similar patterns of enzymatic activity were previously
shown in the context of lung IR injury. This temporal activation may indicate an
involvement of eNOS in an early reparative response, and possibly the late
pathological response, mediated by the coinduction of iNOS-COX-2.
PMID- 24354411
TI - Women's reasons for attrition from a nurse home visiting program.
AB - OBJECTIVE: To describe mothers' reasons for leaving a home visiting program
early. DESIGN: Qualitative descriptive study using semistructured interviews of
mothers who dropped out of the Nurse-Family Partnership (NFP) and two focus
groups with nurses and nurse supervisors at an NFP site. SETTING: A New York
State site of a NFP home visitation program for low-income new mothers designed
to improve the physical and emotional care of children. PARTICIPANTS:
Participants included 21 mothers, 8 nurses, and 3 nurse-supervisors. METHODS:
Semistructured interviews and focus groups were used to collect data, which were
analyzed using content analysis. RESULTS: The program was not perceived to fit a
mother's needs when she was overwhelmed with other responsibilities, the nurse
did not meet her expectations, the content was not of interest, or the mother did
not desire visits after the infant was born. Nurses and mothers described the
need for mothers to have organizational and communication skills, such as keeping
track of appointments, calling to reschedule, articulating needs, and asking for
assistance. Disruptive external influences included nurse turnover and unstable
living situations, including frequent moves and crowded housing. Each of these
types of barriers had potential to interact with the others, creating complex
combinations of challenges to retention. CONCLUSION: NFP retention might be
improved by reframing program relevance to individual mothers and increasing
maternal organizational and communication skill development.
PMID- 24354412
TI - Pattern of bone erosion and bone proliferation in psoriatic arthritis hands: a
high-resolution computed tomography and radiography follow-up study during
adalimumab therapy.
AB - OBJECTIVES: To investigate the pattern and development of bone erosion and
proliferation in patients with psoriatic arthritis (PsA) during treatment with
adalimumab, using high-resolution computed tomography (CT) and conventional
radiography. METHOD: Forty-one biologic-naive PsA patients were initiated with
adalimumab 40 mg subcutaneously every other week. CT and radiography of the 2nd
5th metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal
interphalangeal (DIP) joints were conducted at baseline (n = 41) and after 24
weeks (n = 32). Changes in bone erosion and proliferation are described and the
imaging modalities compared. RESULTS: Ninety percent of bone erosions detected by
CT were located in the metacarpal heads, and most frequently in the 2nd-3rd MCP
joints. Radial (37%) and ulnar (31%) surfaces were more frequently eroded than
dorsal (10%) and palmar (22%) sites. Using CT, bone proliferations were located
primarily on the sides of the distal part of the DIP joints (43% of all
proliferations), but also proximally in DIP (17%) and MCP joints (27%). For bone
erosions and proliferations, respectively, radiography showed a low sensitivity
(17% and 26%), but a high specificity (98% and 95%) and accuracy (93% and 87%),
with CT as the gold standard reference. Neither CT nor radiography revealed
statistically significant changes in bone erosion or proliferation scores between
baseline and follow-up. CONCLUSIONS: Patterns of bone erosion and proliferation
in PsA hands were revealed in more detail by CT than by radiography. No overall
progression or repair could be detected during adalimumab treatment with either
of the methods.
PMID- 24354413
TI - Antihypertensive mechanism of lactoferrin-derived peptides: angiotensin receptor
blocking effect.
AB - Looking for antihypertensive mechanisms beyond ACE inhibition, we assessed
whether lactoferrin (LF)-derived peptides can act as receptor blockers to inhibit
vasoconstriction induced by angiotensin II or endothelin-1. The lactoferricin B
(LfcinB)-derived peptide LfcinB20-25 (RRWQWR), the low molecular weight LF
hydrolysate (LFH < 3 kDa), and two peptides identified in LFH < 3 kDa (LIWKL and
RPYL) were tested in ex vivo assays of vasoactive responses. The peptide RPYL was
tested in radioligand receptor binding assays. Both LFH < 3 kDa and individual
peptides inhibited angiotensin II-induced vasoconstriction. RPYL showed the
highest ex vivo inhibitory effect and also inhibited binding of [(125)I]
(Sar(1),Ile(8))-angiotensin II to AT1 receptors. By contrast, neither LFH < 3 kDa
nor RPYL inhibited endothelin-1 and depolarization-induced vasoconstrictions. In
conclusion, LF-derived peptides selectively inhibit angiotensin II-induced
vasoconstriction by blocking angiotensin AT1 receptors. Therefore, inhibition of
angiotensin II-induced vasocontriction is suggested as a mechanism contributing
along with ACE inhibition to the antihypertensive effect of some LF-derived
peptides.
PMID- 24354414
TI - Basic nursing care: retrospective evaluation of communication and psychosocial
interventions documented by nurses in the acute care setting.
AB - PURPOSE: This study aimed to evaluate the frequency of psychosocial aspects of
basic nursing care, as e-charted by nurses, when using an interface terminology.
METHODS: An observational, multicentre study was conducted in acute wards. The
main outcome measure was the frequency of use of the psychosocial interventions
in the electronic nursing care plans, analysed over a 12 month retrospective
review. FINDINGS: Overall, 150,494 electronic care plans were studied. Most of
the intervention concepts from the interface terminology were used by registered
nurses to illustrate the psychosocial aspects of fundamentals of care in the
electronic care plans. CONCLUSIONS AND IMPLICATIONS: The results presented help
to demonstrate that the interventions of this interface terminology may be useful
to inform psychosocial aspects of basic and advanced nursing care. CLINICAL
RELEVANCE: The identification of psychosocial elements of basic nursing care in
the nursing documentation may lead to obtain a deeper understanding of those
caring interventions nurses consider essential to represent nurse-patient
interactions. The frequency of psychosocial interventions may contribute to
delineate basic and advanced nursing care.
PMID- 24354415
TI - Monocyte depletion increases local proliferation of macrophage subsets after
skeletal muscle injury.
AB - BACKGROUND: Sequential accumulation of M1 and M2 macrophages is critical for
skeletal muscle recovery after an acute injury. While M1 accumulation is believed
to rely on monocyte infiltration, the mechanisms of M2 accumulation remain
controversial, but could involve an infiltrating precursor. Yet, strong depletion
of monocytes only partially impairs skeletal muscle healing, supporting the
existence of alternative mechanisms to palliate the loss of infiltrating
macrophage progenitors. The aims of this study are thus to investigate if
proliferation occurs in macrophage subsets within injured skeletal muscles; and
to determine if monocyte depletion leads to increased proliferation of
macrophages after injury. METHODS: Injury was induced by bupivacaine injection in
the tibialis anterior muscle of rats. Blood monocytes were depleted by daily
intravenous injections of liposome-encapsulated clodronate, starting 24 h prior
to injury. In separate experiments, irradiation of hind limb was also performed
to prevent resident cell proliferation. Upon euthanasia, blood and muscles were
collected for flow cytometric analyses of macrophage/monocyte subsets. RESULTS:
Clodronate induced a 80%-90% depletion of monocyte but only led to 57% and 41%
decrease of M1 and M2 macrophage accumulation, respectively, 2 d following
injury. Conversely, the number of M1 macrophages in monocyte-depleted rats was
2.4-fold higher than in non-depleted rats 4 d after injury. This was associated
with a 16-fold increase in the number of proliferative M1 macrophages, which was
reduced by 46% in irradiated animals. Proliferation of M2 macrophages was
increased tenfold by clodronate treatment 4 d post injury. The accumulation of M2
macrophages was partially impaired by irradiation, regardless of monocyte
depletion. CONCLUSIONS: M1 and M2 subsets proliferate after skeletal muscle
injury and their proliferation is enhanced under condition of monocyte depletion.
Our study supports the conclusion that both infiltrating and resident precursors
could contribute to M1 or M2 macrophage accumulation in muscle injury.
PMID- 24354416
TI - The effects of luteolin on the intestinal ischemia/reperfusion injury in mice.
AB - The purpose of this study is to investigate the potential protective effect of
the flavonoid Luteolin on ischemia-reperfusion (IR) injury in mouse intestine,
which has not previously been studied. Twenty-four female C57BL/6 mice were
randomly assigned to four groups, each consisting of 6 mice: a sham group
(laparotomy, but no IR injury), a sham + Luteolin group (no IR, and Luteolin was
administered intraperitoneally 30 min after laparotomy), IR group (30 min
occlusion of the superior mesenteric artery (SMA) then 2 hr' reperfusion), IR +
Luteolin (30 min occlusion of the SMA then 2 hr' reperfusion; Luteolin was
administered intraperitoneally before reperfusion). Intestine tissues were
harvested from the mice for histopathological and biochemical analysis. Total
oxidant status (TOS) and total antioxidant capacity (TAC) of the intestinal
tissues were measured using Erel's method. Oxidative stress index (OSI) was
calculated using the TOS/TAC ratio. Intestinal histological changes were
significantly decreased in the IR + Luteolin group compared with the IR group (p
= .037). TOS tissue levels were also significantly decreased in the IR + Luteolin
group compared with the IR group (p = .005). TAC levels did not increase
significantly in the IR treatment group and were not affected by Luteolin
treatment (p > .05). The results of this study show that Luteolin administration
provides considerable protection against IR injury in the mouse intestine.
PMID- 24354417
TI - Regression and classification methods for nasolabial folds: a possible paradigm
for computer-aided diagnosis of skin diseases.
AB - Classification of facial features, for example, nasolabial folds, still relies
mainly on clinical assessment, resulting in significant costs because of high
intra- and interrater variability. Further, diagnosing skin diseases, for
example, malignant melanoma, also can present challenges. In an attempt to reduce
cost of medical care in future, we determined the utility of methods in image
processing and statistical analysis to automatically quantify, for example, the
structure of nasolabial folds. To the best of our knowledge, this is the first
report of the application of computer technology to grading of nasolabial folds.
When classifying severity of wrinkles on a scale of 1-5, the computer achieved an
accuracy of 87% compared to the dermatologist, taken as the gold standard.
Further, the computer program's capacity to sort the order of wrinkles from least
to most wrinkled was 98% as accurate as the clinician(s). We conclude that by
using computer technology, nasolabial folds can be categorized almost as
accurately as by using grading by dermatologists, suggesting that computer
technology may be a useful tool to grade nasolabial folds because a computer is
always consistent. We hypothesize that, after additional studies, this technology
also may be a useful tool to aid in diagnosing skin diseases.
PMID- 24354418
TI - The energy density of laser light differentially modulates the skin morphological
reorganization in a murine model of healing by secondary intention.
AB - This study investigates the influence of gallium-arsenide (GaAs) laser
photobiostimulation applied with different energy densities on skin wound healing
by secondary intention in rats. Three circular wounds, 10 mm in diameter, were
made on the dorsolateral region of 21 Wistar rats weighting 282.12 +/- 36.08 g.
The animals were equally randomized into three groups: Group SAL, saline solution
0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses
of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and
wound contraction were performed on the scar tissue from different wounds every 7
days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and
glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres
were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen
fibres were predominant at day 7 in both groups. There was gradual reduction in
these fibres and accumulation of type-I collagen over time, especially in L3 and
L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days
7 and 14 compared to the other groups (P < 0.05). On these same days, there was
higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of
wound closure during all time points investigated was higher in the L30 group (P
< 0.05). Both energy densities investigated increased the tissue cellularity,
vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis,
with the greater benefits for wound closure being found at the density of 30
J/cm(2).
PMID- 24354419
TI - Effect of amino group charge on the photooxidation kinetics of aromatic amino
acids.
AB - The kinetics of the photooxidation of aromatic amino acids histidine (His),
tyrosine (Tyr), and tryptophan (Trp) by 3,3',4,4'-benzophenonetetracarboxylic
acid (TCBP) has been investigated in aqueous solutions using time-resolved laser
flash photolysis and time-resolved chemically induced dynamic nuclear
polarization. The pH dependence of quenching rate constants is measured within a
large pH range. The chemical reactivities of free His, Trp, and Tyr and of their
acetylated derivatives, N-AcHis, N-AcTyr, and N-AcTrp, toward TCBP triplets are
compared to reveal the influence of amino group charge on the oxidation of
aromatic amino acids. The bimolecular rate constants of quenching reactions
between the triplet-excited TCBP in the fully deprotonated state and tryptophan,
histidine, and tyrosine with a positively charged amino group are kq = 2.2 *
10(9) M(-1) s(-1) (4.9 < pH < 9.4), kq = 1.6 * 10(9) M(-1) s(-1) (6.0 < pH <
9.2), and kq = 1.5 * 10(9) M(-1) s(-1) (4.9 < pH < 9.0), respectively.
Tryptophan, histidine, and tyrosine with a neutral amino group quench the TCBP
triplets with the corresponding rate constants kq = 8.0 * 10(8) M(-1) s(-1) (pH >
9.4), kq = 3.0 * 10(8) M(-1) s(-1) (pH > 9.2), and kq = (4.0-10.0) * 10(8) M(-1)
s(-1) (9.0 < pH < 10.1) that are close to those for the N-acetylated derivatives.
Thus, it has been established that the presence of charged amino group changes
oxidation rates by a significant factor; i.e., His with a positively charged
amino group quenches the TCBP triplets 5 times more effectively than N-AcHis and
His with a neutral amino group. The efficiency of quenching reaction between the
TCBP triplets and Tyr and Trp with a positively charged amino group is about 3
times as high as that of both Tyr and Trp with a neutral amino group, N-AcTyr and
N-AcTrp.
PMID- 24354420
TI - Childhood trauma and the treatment for psychotic disorder.
PMID- 24354421
TI - Technical report: an ePRO patient reported outcome program for the evaluation of
patients with irritable bowel syndrome.
AB - BACKGROUND: Patient reported outcome (PRO) is an important healthcare concept
that describes patient's participation in their care by self-evaluation, usually
in the form of questionnaires. This report describes an unique computerized
technique, electronic PRO (ePRO), for following the progress of patients with
irritable bowel syndrome (IBS). METHODS: Patients first completed a series of
questionnaires, including questions about their illness history, symptom
severity, and, in this application, psychological and relationship issues. The
symptom severity and psychological questionnaires were then completed at
intervals by the patients on their own computers. The ePRO was constructed to
allow scores to be automatically summed and placed on a time-line graph for
review at the time of the next office visit. KEY RESULTS: Of the 32 patients who
completed the initial set of questionnaires, 20 maintained participation in the
program for a 6-month period. Of those 20 patients, median number of submissions
was 7.0; median interval between questionnaire submissions was 3.0 weeks, whereas
median interval between office visits was 5.9 weeks. On average, questionnaire
completion took less than 5 min and was positively experienced by the patients.
CONCLUSIONS & INFERENCES: The ePRO program proved to be technically feasible,
clinically useful, and positively experienced by the patients. It provides a
focus on a collaborative conversation between physician and patient. It has
significant potential as a technique for evaluating outcome in response to
various therapies.
PMID- 24354422
TI - Unexpected deaths in medical wards during night shifts: a narrative analysis of
nursing experiences.
AB - AIMS AND OBJECTIVES: To explore nurses' narratives of unexpected patient deaths
during nightshifts. BACKGROUND: Despite the importance of patient care and safety
during the night, little attention has been paid to this issue in scientific
literature. Very few studies have investigated the outcome of night-time nursing
care in patients, and there is a distinct paucity of knowledge regarding the
experiences of nurses who discover a patient who has died unexpectedly during a
night shift. DESIGN: A qualitative study design using semi-structured interviews,
interpreted by a narrative inquiry methodology, was adopted. METHODS: A
purposeful sample of 15 nurses working in Italian medical wards who had found a
patient who had died unexpectedly during a night shift, and who had given their
informed consent were interviewed in the period from 2009-2011. An inductive
content analysis of the narrated experiences was performed. FINDINGS: A patient's
unexpected death during a night shift is something that nurses fear, and when it
occurs, the experience is remembered as a nightmare. From the narratives of the
participant nurses, five categories described what happened at night when a
patient who had died unexpectedly was discovered: (1) the night started by nurses
selecting patients needing intensive surveillance; (2) patients were
reprioritised for intensive surveillance; (3) nurses were deceived by apparently
normal findings; (4) nurses realised the failure of their protective role; and
(5) as a consequence, more intrusive surveillance measures were adopted after the
event. CONCLUSIONS: From the narratives, a number of failures in cumulative and
individual surveillance occurred during the night when a patient died
unexpectedly. The deaths were recognised late, causing intense pain in nurses;
this experience affected the following night shifts, when the nurses'
surveillance was more intensive, insistent and intrusive towards patients, even
if this was unnecessary. RELEVANCE TO CLINICAL PRACTICE: The continuing belief
that the night shift is a time when fewer nurses are needed means that the number
of registered nurses is reduced and reliance is placed on nursing aides instead,
placing patients at risk by compromising the effectiveness of surveillance and
the consequent clinical decisions made by nurses and physicians.
PMID- 24354423
TI - Cor triatriatum sinistrum presenting as cardioembolic stroke: an unusual cause of
adolescent hemiparesis.
AB - Cor triatriatum sinistrum is a rare congenital cardiac malformation, in which the
left atrium (LA) is divided into two distinct chambers by a fibromuscular
membrane. Classically, the proximal (upper or superior) chamber of the LA
receives pulmonary venous connections, whereas the distal (lower or inferior)
chamber contains LA appendage and true atrial septum containing fossa ovalis. The
distal chamber is in continuity with the atrioventricular valve, while the two
chambers communicate through a defect in the membrane. The hemodynamics of cor
triatriatum sinistrum are similar to that of mitral stenosis due to obstructive
property of membrane. The majority of reported cases of cor triatriatum occur in
infants with symptoms of pulmonary venous obstruction, with adult cases being
rare. Herein, we describe an unusual case of cor triatriatum in a 17-year-old boy
who presented for the first time with embolic cerebral infarction with left
hemiparesis.
PMID- 24354424
TI - Sexual challenges with aging: integrating the GES approach in an elderly couple.
AB - An advantage of sexuality after 60 years of age is the increased need for couple
involvement to promote desire, pleasure, eroticism, and satisfaction inherent to
the healthy aging process. This case study clinically explores the complex
psychobiosocial interactions for understanding, assessing, and treating sexual
problems for couples age 60 years and older, emphasizing the Good Enough Sex
approach of variable, flexible, and shared sexual pleasure. Aging couples are
discouraged from appraising their sexual experiences within the parameters of the
pass/fail binary of the traditional individual performance model and are instead
encouraged to embrace the evolving elasticity of their sexual experiences. The
Good Enough Sex model espouses an approachable and satisfying alternative for the
promotion of sexual function and satisfaction throughout the life span, with
particular interest in late adulthood sexual health.
PMID- 24354425
TI - Lung cancer presenting as thin-walled cysts: An analysis of 15 cases and review
of literature.
AB - AIM: Lung cancer presenting as cysts is a rare entity in clinical practice.
Differential diagnosis is difficult in the benign-like cyst. METHODS: We
conducted a retrospective analysis of the clinical records of 15 patients who
underwent surgery for primary lung cancer presenting as cysts (wall thickness <5
mm) in our department between 2007 and 2012. The whole group underwent
postoperative follow-up. RESULTS: The subjects' age ranged from 18 to 80 years
with a median age of 58.3 years. Eight cases presented with respiratory symptoms
while seven showed abnormal shadows on a chest computed tomography without
symptoms. Histological analysis showed that 10 cases were of adenocarcinoma, two
of squamous cell carcinoma and one of large cell carcinoma. Two patients died at
13 and 26 months and the remaining 13 patients are alive and disease free at 3-38
months. CONCLUSION: Cystic lung cancer should be considered in the differential
diagnosis of focal benign cyst. Cystic lung cancer could achieve a good outcome
if early diagnosis can be obtained.
PMID- 24354426
TI - Quantitative and qualitative differences in celiac disease epitopes among durum
wheat varieties identified through deep RNA-amplicon sequencing.
AB - BACKGROUND: Wheat gluten is important for the industrial quality of bread wheat
(Triticum aestivum L.) and durum wheat (T. turgidum L.). Gluten proteins are also
the source of immunogenic peptides that can trigger a T cell reaction in celiac
disease (CD) patients, leading to inflammatory responses in the small intestine.
Various peptides with three major T cell epitopes involved in CD are derived from
alpha-gliadin fraction of gluten. Alpha-gliadins are encoded by a large multigene
family and amino acid variation in the CD epitopes is known to influence the
immunogenicity of individual gene family members. Current commercial methods of
gluten detection are unable to distinguish between immunogenic and non
immunogenic CD epitope variants and thus to accurately quantify the overall CD
epitope load of a given wheat variety. Such quantification is indispensable for
correct selection of wheat varieties with low potential to cause CD. RESULTS: A
454 RNA-amplicon sequencing method was developed for alpha-gliadin transcripts
encompassing the three major CD epitopes and their variants. The method was used
to screen developing grains on plants of 61 different durum wheat cultivars and
accessions. A dedicated sequence analysis pipeline returned a total of 304 unique
alpha-gliadin transcripts, corresponding to a total of 171 'unique deduced
protein fragments' of alpha-gliadins. The numbers of these fragments obtained in
each plant were used to calculate quantitative and quantitative differences
between the CD epitopes expressed in the endosperm of these wheat plants. A few
plants showed a lower fraction of CD epitope-encoding alpha-gliadin transcripts,
but none were free of CD epitopes. CONCLUSIONS: The dedicated 454 RNA-amplicon
sequencing method enables 1) the grouping of wheat plants according to the
genetic variation in alpha-gliadin transcripts, and 2) the screening for plants
which are potentially less CD-immunogenic. The resulting alpha-gliadin sequence
database will be useful as a reference in proteomics analysis regarding the
immunogenic potential of mature wheat grains.
PMID- 24354428
TI - Growth and crystallographic feature-dependent characterization of spinel zinc
ferrite thin films by RF sputtering.
AB - ZnFe2O4 (ZFO) thin films exhibiting varying crystallographic features ((222)
epitaxially, (400)-epitaxially, and randomly oriented films) were grown on
various substrates by radio-frequency magnetron sputtering. The type of substrate
used profoundly affected the surface topography of the resulting ZFO films. The
surface of the ZFO (222) epilayer was dense and exhibited small rectangular
surface grains; however, the ZFO (400) epilayer exhibited small grooves. The
surface of the randomly oriented ZFO thin film exhibited distinct three
dimensional island-like grains that demonstrated considerable surface roughness.
Magnetization-temperature curves revealed that the ZFO thin films exhibited a
spin-glass transition temperature of approximately 40 K. The crystallographic
orientation of the ZFO thin films strongly affected magnetic anisotropy. The ZFO
(222) epitaxy exhibited the strongest magnetic anisotropy, whereas the randomly
oriented ZFO thin film exhibited no clear magnetic anisotropy.
PMID- 24354427
TI - Adaptations underlying the development of excessive alcohol intake in selectively
bred mice.
AB - BACKGROUND: This commentary discusses the important contributions of the article
in this issue by Matson and colleagues entitled "Selectively bred crossed high
alcohol-preferring mice drink to intoxication and develop functional tolerance,
but not locomotor sensitization during free-choice ethanol access" as well as
providing comparison to studies on other drugs of abuse. METHODS: The findings of
the target article are evaluated and compared to the larger literature of intake
escalation and vulnerability to addiction observed with other drugs of abuse.
RESULTS: In their study, Matson and colleagues report that mice derived by
crossing different lines selectively bred for high alcohol intake exhibit initial
alcohol intakes associated with motor impairment followed by marked escalation of
consumption and tolerance to the effects of alcohol on motor coordination. In
contrast, no evidence of pharmacokinetic tolerance or sensitization of alcohol
induced locomotion was observed. These results demonstrate that the cHAP mice
constitute an appropriate model for the study of excessive drinking, which is
produced by escalated alcohol intake and functional changes, leading to excessive
intoxication. CONCLUSIONS: Future work should assess adaptations in motivational
processes and subjective effects of alcohol as well as the potential genetic and
epigenetic bases of escalated alcohol intake.
PMID- 24354429
TI - Dioxatricyclic and oxabicyclic polyketides from Trichocladium opacum.
AB - Five new polyketides, trichocladinols D-H (1-5) with dioxatricyclic (1-3) and
oxabicyclic (4 and 5) skeletons, and the known massarilactone C (6) were isolated
from the solid-substrate fermentation cultures of the ascomycete fungus
Trichocladium opacum. The structures of 1-5 were determined mainly by NMR
experiments, and 1, 3, and 4 were confirmed by X-ray crystallography. The
absolute configurations of 1 and 3 were assigned by X-ray crystallography using
Cu Kalpha radiation, whereas that of C-5 in 2 and 4 was deduced via the circular
dichroism (CD) data. Compounds 2-4 showed weak cytotoxicity against the human
tumor cell lines A549, HCT116, and SW480.
PMID- 24354430
TI - Concussion management by paediatricians: a national survey of Canadian
paediatricians.
AB - OBJECTIVE: To assess the use of concussion/mild traumatic brain injury (mTBI)
guidelines, criteria used in the initiation of return-to-play (RTP) and
management of RTP for brain injured children and youth by Canadian
paediatricians. METHODS: A cross-sectional survey was mailed through the Canadian
Paediatric Surveillance Program to ~2600 paediatric specialists and sub
specialists. RESULTS: Of 809 respondents (31%), 503 encountered newly diagnosed
paediatric concussion/mTBI within the past 12 months, reporting ~6900 cases. Of
the respondents, 96.7% (95% CI = 94.7-98.6%) reported using one or more of the
presented concussion/mTBI guidelines in the management of their patients. The
most frequently reported criteria (>50%) used to determine asymptomatic status
were: free from all concussion symptoms, by patient report (92%), by proxy report
(76%), normal physical examination (65%), in school full-time, with usual school
performance (53%). Most respondents (84.9%) did not initiate RTP immediately
after their patients became asymptomatic. The median time waiting before
initiating RTP was 7 days. The median duration of the RTP sequence was 7 days,
with considerable variation reported. CONCLUSIONS: Canadian paediatricians
frequently encounter patients with concussion/mTBI. Their concussion/mTBI care
appears to be consistent with current guidelines, but also shows practice
variation, particularly when current guidelines become less proscriptive.
PMID- 24354431
TI - "Gliomatosis encephali" as a novel category of brain tumors by the first autopsy
case report of gliomatosis cerebelli.
AB - Gliomatosis cerebri is a rare diffuse glioma that is neither mass-forming nor
necrotic, and does not disrupt existing structures. Gliomatosis occurring in the
cerebellum is known as gliomatosis cerebelli, and only three such cases examined
by biopsy have been reported. Here we describe the first autopsy findings of a
patient who was diagnosed as having gliomatosis in the cerebellum.
Neuropathological examination identified the tumor cells as being positive for
glial fibrillary acidic protein, vimentin and nestin, with atypical nuclei that
were cashew-nut- or dishcloth-gourd-shaped. These tumor cells were dense in the
right cerebellum, but also spread broadly throughout the brain including the left
cerebrum and optic nerve. Mitotic figures were frequently seen in the cerebellum,
brain stem and cerebrum. Scherer's secondary structures were evident not only in
the cerebellum but also the cerebrum. No necrosis, microvascular proliferation or
destruction of anatomical structures was detected in the whole brain. Differences
in the origin of the tumors of the gliomatoses cerbri and cerebelli suggests
these tumors are different types of brain tumors. Thus the findings support that
the gliomatosis cerebelli is a novel type of brain tumor classification.
Furthermore, by the similarities of the histological features among the tumors,
it appears appropriate to establish a novel category of "gliomatosis encephali"
which includes both gliomatosis cerebri and gliomatosis cerebelli.
PMID- 24354432
TI - Antagonistic interaction networks are structured independently of latitude and
host guild.
AB - An increase in species richness with decreasing latitude is a prominent pattern
in nature. However, it remains unclear whether there are corresponding
latitudinal gradients in the properties of ecological interaction networks. We
investigated the structure of 216 quantitative antagonistic networks comprising
insect hosts and their parasitoids, drawn from 28 studies from the High Arctic to
the tropics. Key metrics of network structure were strongly affected by the size
of the interaction matrix (i.e. the total number of interactions documented
between individuals) and by the taxonomic diversity of the host taxa involved.
After controlling for these sampling effects, quantitative networks showed no
consistent structural patterns across latitude and host guilds, suggesting that
there may be basic rules for how sets of antagonists interact with resource
species. Furthermore, the strong association between network size and structure
implies that many apparent spatial and temporal variations in network structure
may prove to be artefacts.
PMID- 24354433
TI - Chemokine CXCL-1 expression in the subretinal fluid during rhegmatogenous retinal
detachment.
AB - PURPOSE: To investigate the expression of chemokine CXCL-1 in the subretinal
fluid (SRF) during rhegmatogenous retinal detachment (RRD) and identify potential
correlations with number of quadrants involved and duration of the detachment.
METHODS AND RESULTS: Inclusion criteria were patients aged 18 years or older and
primary RRD possibly complicated by proliferative vitreoretinopathy (PVR). CXCL-1
levels were measured in 36 SRF samples from 36 RRD patients. Mean CXCL-1 levels
(102 +/- 37 pg/mL) were significantly higher (p = 0.050) compared to controls.
CXCL-1 levels correlated significantly with age (p = 0.001) and RRD duration (p =
0.002). Maximum CXCL-1 levels coincided with total RRD, 29- to 60-day duration
and PVR grade C. CONCLUSIONS: The findings of this study may contribute to
increased understanding regarding the role of CXCL-1 during the onset and
progression of the wound healing process in the context of RRD and PVR.
PMID- 24354434
TI - Factors associated with dental caries in Brazilian children: a multilevel
approach.
AB - OBJECTIVES: The aims of the present study were to assess caries experience among
Brazilian children aged eight to 10 years and determine social factors of this
disease, through a multilevel approach. METHODS: This is a cross-sectional study
in which a representative sample of 1204 eight-to-ten-year-old children were
randomly selected from 19 public and private schools in the city of Belo
Horizonte, Brazil. After formal authorization from the parents, the children were
clinically examined at school by two calibrated examiners (Kappa=0.78).
Individual socioeconomic status was determined using household income, number of
residents in the home and parents'/caregivers' schooling. The social
vulnerability index and type of school were used as contextual variables. The
outcome variables were severity score of dental caries in permanent teeth (DMFT
index), dental caries experience in permanent teeth (DMFT = 0 or ? 0), severity
score of dental caries in primary teeth (dmft index) and dental caries experience
in primary teeth (dmft = 0 or ? 0). RESULTS: The minority of children (37.2%) had
dental caries experience. Chi-squared and Mann-Whitney tests showed that age,
parents'/caregivers' schooling, household income and type of school were
associated with dental caries experience in permanent and primary teeth (P <
0.05). Mann-Whitney, Kruskal-Wallis tests and Spearman correlation coefficient
showed that age, parents'/caregivers' schooling, household income, and type of
school were associated with severity score of dental caries in permanent and
primary teeth (P < 0.05). In multilevel approach, the individual variables, age
and household income demonstrated association with dental caries experience and
with severity score of dental caries in primary teeth (P < 0.05). Type of school
was also associated with dental caries experience and with severity score of
dental caries in these teeth (P < 0.05). In the Poisson multilevel approach, the
analysis of the final estimation of variance components of the null model
revealed a significant difference among the 19 schools with regard to severity
score of dental caries in permanent teeth too (P < 0.001). Younger children and
attending private schools showed lower severity score of dental caries in
permanent teeth. CONCLUSION: Dental caries experience and severity score of
dental caries in primary teeth was influenced by age, household income, and the
type of school The dental caries experience in permanent teeth was influenced by
age, parents'/caregivers' schooling, household income, and type of school,
whereas the severity score of dental caries in permanent teeth was influenced by
age and type of school.
PMID- 24354435
TI - RNA polymerase II subunits exhibit a broad distribution of macromolecular
assembly states in the interchromatin space of cell nuclei.
AB - Nearly all cellular processes are enacted by multi-subunit protein complexes, yet
the assembly mechanism of most complexes is not well understood. The
anthropomorphism "protein recruitment" that is used to describe the concerted
binding of proteins to accomplish a specific function conceals significant
uncertainty about the underlying physical phenomena and chemical interactions
governing the formation of macromolecular complexes. We address this deficiency
by investigating the diffusion dynamics of two RNA polymerase II subunits, Rpb3
and Rpb9, in regions of live Drosophila cell nuclei that are devoid of chromatin
binding sites. Using FRAP microscopy, we demonstrate that both unengaged subunits
are incorporated into a broad distribution of complexes, with sizes ranging from
free (unincorporated) proteins to those that have been predicted for fully
assembled gene transcription units. In live cells, Rpb3 exhibits regions of
stability at both size extremes connected by a continuous distribution of
complexes. Corresponding measurements on cellular extracts reveal a distribution
that retains peaks at the extremes but not in between, suggesting that partially
assembled complexes are less stable. We propose that the broad distribution of
macromolecular species allows for mechanistic flexibility in the assembly of
transcription complexes.
PMID- 24354436
TI - Neurotransmitter detection using corona phase molecular recognition on
fluorescent single-walled carbon nanotube sensors.
AB - Temporal and spatial changes in neurotransmitter concentrations are central to
information processing in neural networks. Therefore, biosensors for
neurotransmitters are essential tools for neuroscience. In this work, we applied
a new technique, corona phase molecular recognition (CoPhMoRe), to identify
adsorbed polymer phases on fluorescent single-walled carbon nanotubes (SWCNTs)
that allow for the selective detection of specific neurotransmitters, including
dopamine. We functionalized and suspended SWCNTs with a library of different
polymers (n = 30) containing phospholipids, nucleic acids, and amphiphilic
polymers to study how neurotransmitters modulate the resulting band gap, near
infrared (nIR) fluorescence of the SWCNT. We identified several corona phases
that enable the selective detection of neurotransmitters. Catecholamines such as
dopamine increased the fluorescence of specific single-stranded DNA- and RNA
wrapped SWCNTs by 58-80% upon addition of 100 MUM dopamine depending on the SWCNT
chirality (n,m). In solution, the limit of detection was 11 nM [K(d) = 433 nM for
(GT)15 DNA-wrapped SWCNTs]. Mechanistic studies revealed that this turn-on
response is due to an increase in fluorescence quantum yield and not covalent
modification of the SWCNT or scavenging of reactive oxygen species. When
immobilized on a surface, the fluorescence intensity of a single DNA- or RNA
wrapped SWCNT is enhanced by a factor of up to 5.39 +/- 1.44, whereby
fluorescence signals are reversible. Our findings indicate that certain DNA/RNA
coronae act as conformational switches on SWCNTs, which reversibly modulate the
SWCNT fluorescence. These findings suggest that our polymer-SWCNT constructs can
act as fluorescent neurotransmitter sensors in the tissue-compatible nIR optical
window, which may find applications in neuroscience.
PMID- 24354437
TI - Trait self-control predicts adolescents' exposure and reactivity to daily
stressful events.
AB - The current study used an influence model of personality and stress processes to
examine the association between individual differences in trait self-control and
daily stress exposure and reactivity in adolescent youth. A total of 129
adolescents (Mage = 14.7 years, 59% female) completed individual difference
measures of self-control, neuroticism, and measures of responses to stress.
Participants then reported on daily stressful events, stress severity, mood,
coping, and mindlessness (a predictor of acting on impulse) for 14 consecutive
days. Self-control predicted less exposure to daily stress, less reactivity to
daily stress, and more adaptive responses to stress. Specifically, adolescents
with higher self-control experienced fewer daily stressors and reported lower
stress severity, particularly when daily mindlessness was high. Second,
adolescents with higher self-control reported less mindlessness in response to
daily stress relative to those with lower self-control, but they did not show
differences in emotional reactivity to stress. Finally, results also offered
evidence for an indirect effect of problem-focused coping strategies between self
control and emotional reactivity to stress. The current investigation illustrates
the importance of trait self-control in daily stress processes among adolescents
and suggests possible mechanisms through which self-control confers these
positive effects.
PMID- 24354438
TI - Early rheumatoid arthritis 6 years after diagnosis is still associated with high
direct costs and increasing loss of productivity: the Swedish TIRA project.
AB - OBJECTIVES: To calculate total costs over 6 years after diagnosis of early
rheumatoid arthritis (RA). METHOD: In the longitudinal prospective multicentre
TIRA study, 239 patients from seven units, diagnosed in 1996-98, reported
regularly on health-care utilization and the number of days lost from work. Costs
were obtained from official databases and calculated using unit costs (Swedish
kronor, SEK) from 2001. Indirect costs were calculated using the human capital
approach (HCA). Costs were inflation adjusted to Euro June 2012, using the
Swedish Consumer Price Index and the exchange rate of June 2012. Statistical
analyses were based on linear mixed models (LMMs) for changes over time. RESULTS:
The mean total cost per patient was EUR 14,768 in year 1, increasing to EUR
18,438 in year 6. Outpatient visits and hospitalization decreased but costs for
surgery increased from EUR 92/patient in year 1 to EUR 444/patient in year 6.
Drug costs increased from EUR 429/patient to EUR 2214/patient, mainly because of
the introduction of biologics. In year 1, drugs made up for 10% of direct costs,
and increased to 49% in year 6. Sick leave decreased during the first years but
disability pensions increased, resulting in unchanged indirect costs. Over the
following years, disability pensions increased further and indirect costs
increased from EUR 10,284 in year 1 to EUR 13,874 in year 6. LMM analyses showed
that indirect costs were unchanged whereas direct costs, after an initial fall,
increased over the following years, leading to increasing total costs.
CONCLUSIONS: In the 6 years after diagnosis of early RA, drug costs were
partially offset by decreasing outpatient visits but indirect costs remained
unchanged and total costs increased.
PMID- 24354439
TI - Diversities and complexities in the health of Asian women.
PMID- 24354440
TI - Concurrent incidence of adverse events in hospitals and nursing homes.
AB - PURPOSE: To describe the concurrent incidence of pressure ulcers, urinary tract
infections, and falls in hospitals and nursing homes, and the preventive care
given. Additionally, the correlation between the occurrence of these adverse
events and preventive care was explored. DESIGN AND SETTINGS: A prospective, 3
month, cohort study at 10 hospitals and 10 nursing homes in the Netherlands.
PARTICIPANTS: 687 hospital patients and 241 nursing home patients. MAIN OUTCOME
MEASURES: The incidence of three adverse events and preventive care given to
patients at risk. During weekly visits, the patients and their files were
assessed. Additionally, observations were performed. RESULTS: Seventy-seven
hospital patients (11%) and 111 nursing home patients (46%) developed one or more
adverse events. The incidence rate for both types of patients, and for the three
adverse events combined, was 9% adverse events per patient week. In hospitals,
34% of the patients received adequate pressure ulcer preventive care, while 47%
of the patients received adequate urinary tract infection preventive care, and
none of the patients received adequate falls preventive care. In nursing homes,
18% of the patients received adequate pressure ulcer preventive care, 42% of the
patients received adequate urinary tract infection preventive care, and less than
1% of the patients received adequate falls prevention care. Negative or no
correlations were found between the incidence rates for the three adverse events.
In nursing homes the incidence of pressure ulcers and preventive care were
positively correlated. CONCLUSIONS: There is a high incidence of adverse events
in hospitals and nursing homes. Many patients at risk do not receive adequate
preventive care.
PMID- 24354441
TI - Does lung development differ in male and female fetuses?
AB - Preterm male infants have a higher incidence of morbidity and mortality due to
respiratory insufficiency than females of the same gestational age. This male
disadvantage could be due to differences in lung architecture; however, few
studies have compared lung architecture in male and female fetuses during late
gestation. Our principal objectives were to compare the morphology of the fetal
lung and the maturity of the surfactant system in preterm male and female
fetuses. Lungs from male (n = 9) and female (n = 11) fetal sheep were collected
at 0.9 of term (131 days of the 145-day gestation) for morphological and
molecular analyses. In separate groups, tracheal liquid was obtained from male (n
= 9) and female (n = 9) fetuses at 0.9 of term for determination of surfactant
phospholipid composition. We found no sex-related differences in body weight,
lung weight, right lung volume, lung tissue and airspace fractions, mean linear
intercept, septal crest density, septal thickness, the proportion of
proliferating and apoptotic cells, and the percentages of collagen or elastin.
The gene expression of surfactant protein -A, -B, -C, and -D and tropoelastin was
similar between sexes. There were no differences in the proportion of the major
phospholipid classes in the tracheal liquid between sexes; however there was a
significantly higher percentage of the phospholipid species phosphatidylinositol
38:5 in males. The greater morbidity and mortality in preterm male lambs do not
appear to be related to differences in lung structure or surfactant phospholipid
synthesis before birth, but may relate to physiological adaptation to air
breathing at birth.
PMID- 24354442
TI - Effects of beta-glucan on colon anastomotic healing in rats given preoperative
irradiation.
AB - BACKGROUND: Radiation therapy is an essential therapeutic modality in the
management of a wide variety of tumors. We aimed to investigate the short-term
effects of pelvic irradiation on the healing of colon anastomoses and to
determine the potential protective effects of beta-glucan in this situation.
MATERIAL AND METHODS: Sixty Wistar albino rats were randomized into three
experimental groups: a control group (n = 20), an irradiation (IR) group (n =
20), and an irradiation+beta-glucan (IR+beta-glucan) group (n = 20). Only
segmental colonic resection and anastomosis were performed on the control group.
The IR group underwent the same surgical procedure as the control group 5 days
after pelvic irradiation. In the IR+beta-glucan group, the same procedure was
applied as in the IR group after beta-glucan administration. The groups were
subdivided into subgroups according to the date of euthanasia (third [n = 10] or
seventh [n = 10] postoperative [PO] day), and anastomotic colonic segments were
resected to evaluate bursting pressures and biochemical and histopathological
parameters. RESULTS: Bursting pressure values were significantly lower in the IR
group (p < .001). Malondialdehyde (MDA) levels were significantly higher in the
IR group, whereas beta-glucan significantly decreased MDA levels on the third PO
day (p < .001). Granulation tissue formation scores were significantly lower in
the IR+beta-glucan group compared with the control group and the IR group (p <
.001). CONCLUSIONS: The results of this study indicate that irradiation has
negative effects on the early healing of colon anastomoses. The administration of
beta-glucan ameliorates these unfavorable effects by altering bursting pressures
and biochemical parameters.
PMID- 24354443
TI - Mastectomy for management of breast cancer in Ibadan, Nigeria.
AB - BACKGROUND: Modified radical mastectomy remains the standard therapeutic surgical
operation for breast cancer in most parts of the world. This retrospective study
reviews mastectomy for management of breast cancer in a surgical oncology
division over a ten year period. METHODS: We reviewed the case records of
consecutive breast cancer patients who underwent mastectomy at the Surgical
Oncology Division, University College Hospital (UCH) Ibadan between November 1999
and October 2009. RESULTS: Of the 1226 newly diagnosed breast cancer patients
over the study period, 431 (35.2%) patients underwent mastectomy making an
average of 43 mastectomies per year. Most patients were young women,
premenopausal, had invasive ductal carcinoma and underwent modified radical
mastectomy as the definitive surgical treatment. Prior to mastectomy, locally
advanced tumors were down staged in about half of the patients that received neo
adjuvant combination chemotherapy. Surgical complication rate was low. The most
frequent operative complication was seroma collection in six percent of patients.
The average hospital stay was ten days and most patients were followed up at the
surgical outpatients department for about two years post-surgery. CONCLUSIONS:
There was low rate of mastectomy in this cohort which could partly be
attributable to late presentation of many patients with inoperable local or
metastatic tumors necessitating only palliative or terminal care. Tumor down
staging with neo-adjuvant chemotherapy enhanced surgical loco-regional tumor
control in some patients. The overall morbidity and the rates of postoperative
events were minimal. Long-term post-operative out-patients follow-up was not
achieved as many patients were lost to follow up after two years of mastectomy.
PMID- 24354444
TI - Synthesis and evaluation of heterocyclic analogues of bromoxynil.
AB - One attractive strategy to discover more active and/or crop-selective herbicides
is to make structural changes to currently registered compounds. This strategy is
especially appealing for those compounds with limited herbicide resistance and
whose chemistry is accompanied with transgenic tools to enable herbicide
tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor
registered for control of broadleaf weeds in several agronomic and specialty
crops. Recently at the University of Tennessee-Knoxville several analogues of
bromoxynil were synthesized including a previously synthesized pyridine (2,6
dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6
dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N
oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of
bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine
max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus),
velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and
pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second
study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the
compounds being applied at 0.56 kg ha(-1). Although all compounds were believed
to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and
pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus
retroflexus. However, application of the pyrimidine herbicide resulted in the
least injury to all species tested. These variations in efficacy were
investigated using molecular docking simulations, which indicate that the
pyridine analogue may form a stronger hydrogen bond in the pocket of the D1
protein than the original bromoxynil. A pyridine analogue was able to control the
glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine
analogues of bromoxynil showed potential to have a different weed control
spectrum compared to bromoxynil. A pyridine analogue of bromoxynil synthesized in
this research controlled several weed species greater than bromoxynil itself,
potentially due to enhanced binding within the PSII binding pocket. Future
research should compare this analogue to bromoxynil using optimized formulations
at higher application rates.
PMID- 24354445
TI - Homozygous missense mutation in the LIPH gene causing autosomal recessive
hypotrichosis simplex in a Chinese patient.
PMID- 24354446
TI - Nutrition and hydration in dying patients: the perceptions of acute care nurses.
AB - AIMS AND OBJECTIVES: To explore the perceptions of nurses regarding the provision
and nonprovision of medical nutrition and hydration during the end stage of life
when death is imminent in the acute care setting. BACKGROUND: When people are
dying, they often experience a loss of appetite and desire for drinking which are
natural processes at this time. The cessation of eating and drinking challenges
both family members and clinical staff. This article builds on previous studies
that describe the perceptions of medical doctors and palliative care nurses
regarding medical nutrition and hydration during the end stage of life when death
is imminent. DESIGN: Qualitative descriptive design. METHODS: This study included
three focus group meetings with ten nurses in an acute care setting in medical,
oncology and haematology units. An interview schedule was used to guide the
discussions. RESULTS: The main theme to emerge from this study was 'finding a
comfort space/ambiguous spaces of unrest' that included four subthemes: (1)
limited involvement in decision-making, (2) comfort vs. discomfort, (3)
uncertainty and (4) the comfort of withdrawing treatment. Finding a comfort space
captures the challenges nurses faced when speaking about the concerns of patients
and family. In this space, there were ambiguities that created unease and unrest:
a reluctance to talk about death; a reluctance to engage with the patient and the
family. CONCLUSIONS: Acute care nurses need to be more cognisant of the
palliative approach to care and become more engaged with decision-making during
the end stage of life when death is imminent. RELEVANCE TO CLINICAL PRACTICE:
Nurses in acute care settings need to be involved in decision-making and advocate
for patients and family during the dying phase. Nurses in acute care need better
understanding about the palliative approach to care and nutrition and hydration
for people who are dying.
PMID- 24354447
TI - Delineation of an octopus-like thrombus attached to the eustachian valve.
AB - Eustachian valve (EV) is a vestige of the valve of the inferior vena cava which
directs the umbilical vein blood through open foramen ovale in fetal life.
Following birth it gradually regresses, but it may persist in variable size,
shape, and thickness as a functionless and benign structure. However, there are
reports suggesting that persistent EV may not be completely innocent. It has been
accused of being a predisposing cause of patent foramen ovale and paradoxical
embolism and also interfering with transseptal interventional procedures. It may
serve as a site of infective vegetations and be mistaken as a tumor or thrombus.
In the present case, an octopus-like thrombus attached to the EV was delineated
with the utility of two-dimensional and real time three-dimensional
transesophageal echocardiography. EV was considered to play an essential role in
preventing potential pulmonary embolism.
PMID- 24354448
TI - Effectiveness and safety of rapid clozapine titration in schizophrenia.
AB - OBJECTIVE: Clinical guidelines recommend slow clozapine dose titration in order
to decrease the risk of seizures and hypotension. The recommendation may delay
adequate control of severe psychotic symptoms. We evaluated the safety and
effectiveness of rapid clozapine titration in patients who had been previously
exposed to the drug and in patients who received clozapine for the first time
after failing to respond to other antipsychotics. METHOD: Analysis of hospital
course of a consecutive cohort of schizophrenia patients (N = 111) who received
25-100 mg of clozapine as needed every 6 h the first treatment day, followed by
upward adjustments of 25-100 mg/day. RESULTS: Symptom control was obtained with
an average dose of 353 +/- 174 mg/day after 4.1 +/- 3.1 days in the 73 patients
previously treated with clozapine. For the 38 patients initially started on other
antipsychotics, the average clozapine dose required for symptom control (409 +/-
188 mg/day) was reached after 7.1 +/- 4.8 days. None of the patients had
seizures, severe hypotension or other major adverse reactions. CONCLUSION: In
this naturalistic cohort study rapid clozapine titration appeared safe and
effective for the treatment of schizophrenia. The results justify controlled
clinical trials of this treatment method.
PMID- 24354449
TI - Wild-type K-ras has a tumour suppressor effect on carcinogen-induced murine
colorectal adenoma formation.
AB - K-ras mutations are found in ~40% of human colorectal adenomas and carcinomas and
contribute to colorectal tumour formation at an early stage. Wild-type K-ras has
been reported to be deleted in some tumours, but the consequences of changes in
wild-type K-ras copy number for experimental colorectal carcinogenesis have not
been investigated. To characterize the effects of K-ras copy number changes on
formation of carcinogen-induced colorectal neoplasms in mice, wild-type (K
ras(+/+) ) and heterozygous K-ras exon 1 knockout (K-ras(+/-) ) mice were given
10 weekly treatments of 1, 2-dimethylhydrazine (DMH) to induce colorectal
tumours. Colorectal expression levels of K-ras 4A and 4B transcripts in K-ras(+/
) mice were ~50% decreased compared with K-ras(+/+) mice. One year after DMH
treatment, survival of K-ras(+/-) mice decreased from 88 to 82% compared with
wild-type mice. Colorectal adenomas significantly increased from 0.52 +/- 0.15 in
K-ras(+/+) mice to 0.87 +/- 0.14 in K-ras(+/-) mice (mean +/- SEM per mouse, P <
0.01); total tumour volume increased 2.13-fold (P < 0.05). Comparing K-ras(+/+)
with K-ras(+/-) murine adenomas, Ki-67-positive proliferating tumour cells
significantly increased from 7.77 +/- 0.64% to 9.15 +/- 0.92% and cleaved caspase
3-positive apoptotic tumour cells decreased from 1.40 +/- 0.37% to 0.80 +/- 0.22%
(mean +/- SEM, P < 0.05 for both). No K-ras or B-raf mutations were detected in
the adenomas. Immunohistochemical studies showed no significant changes in
extracellular signal regulating kinase/mitogen-activated protein kinase
(Erk/MapK) or PI3K/Akt pathway activation in the adenomas. In conclusion, the
data collectively show that a 50% reduction in K-ras gene dosage and RNA
expression promoted experimental colorectal tumourigenesis, consistent with wild
type K-ras having a tumour suppressor effect on carcinogen-induced murine
colorectal adenoma formation.
PMID- 24354450
TI - Abiotic stress-induced accumulation of raffinose in Arabidopsis leaves is
mediated by a single raffinose synthase (RS5, At5g40390).
AB - BACKGROUND: The sucrosylgalactoside oligosaccharide raffinose (Raf, Suc-Gal1)
accumulates in Arabidopsis leaves in response to a myriad of abiotic stresses.
Whilst galactinol synthases (GolS), the first committed enzyme in Raf
biosynthesis are well characterised in Arabidopsis, little is known of the second
biosynthetic gene/enzyme raffinose synthase (RS). Conflicting reports suggest the
existence of either one or six abiotic stress-inducible RSs (RS-1 to -6)
occurring in Arabidopsis. Indirect evidence points to At5g40390 being responsible
for low temperature-induced Raf accumulation in Arabidopsis leaves. RESULTS: By
heterologously expressing At5g40390 in E.coli, we demonstrate that crude extracts
synthesise Raf in vitro, contrary to empty vector controls. Using two independent
loss-of-function mutants for At5g40390 (rs 5-1 and 5-2), we confirm that this RS
is indeed responsible for Raf accumulation during low temperature-acclimation (4
degrees C), as previously reported. Surprisingly, leaves of mutant plants also
fail to accumulate any Raf under diverse abiotic stresses including water
deficit, high salinity, heat shock, and methyl viologen-induced oxidative stress.
Correlated to the lack of Raf under these abiotic stress conditions, both mutant
plants lack the typical stress-induced RafS activity increase observed in the
leaves of wild-type plants. CONCLUSIONS: Collectively our findings point to a
single abiotic stress-induced RS isoform (RS5, At5g40390) being responsible for
Raf biosynthesis in Arabidopsis leaves. However, they do not support a single RS
hypothesis since the seeds of both mutant plants still contained Raf, albeit at
0.5-fold lower concentration than seeds from wild-type plants, suggesting the
existence of at least one other seed-specific RS. These results also
unambiguously discount the existence of six stress-inducible RS isoforms
suggested by recent reports.
PMID- 24354451
TI - Identifying important comorbidity among cancer populations using administrative
data: Prevalence and impact on survival.
AB - AIMS: Our study sought to optimize the identification and investigate the impact
of comorbidity in cancer patients using routinely collected hospitalization data.
METHODS: We undertook an iterative process of classification of important
clinical conditions involving evaluation of relevant literature and consultation
with clinicians. Patients diagnosed with colon, rectal, breast, ovarian, uterine,
stomach, liver, renal or bladder cancers (n = 14,096) between 2006 and 2008 were
identified from the New Zealand Cancer Registry. Conditions were identified using
data on diagnoses from hospital admissions for 5 years prior to cancer diagnosis.
Patients were followed up until end of 2009 using routine mortality data.
Prevalence estimates for each condition by site were calculated. All-cause
mortality impact of common conditions was investigated using Cox regression
models adjusted for age and stage at diagnosis. RESULTS: Patients with liver and
stomach cancers tended to have higher comorbidity and those with breast cancer,
lower comorbidity than other cancer patients. Of the 50 conditions, the most
common were hypertension (prevalence 8.0-20.9%), cardiac conditions (2.1-13.5%)
and diabetes with (2.3-13.3%) and without (2.9-12.9%) complications. Comorbidity
was associated with higher all-cause mortality but the impact varied by condition
and across cancer site, with impact less for cancers with poor prognoses.
Conditions most consistently associated with adverse outcomes across all cancer
sites were renal disease, coagulopathies and congestive heart failure.
CONCLUSION: Comorbidity is highly prevalent in cancer populations, but prevalence
and impact of conditions differ markedly by cancer type.
PMID- 24354452
TI - First ring formation by radical addition of propargyl to but-1-ene-3-yne in
combustion. Theoretical study of the C7H7 radical system.
AB - Combustive formation of a first carbon ring is an important step in the growth of
polycyclic aromatic hydrocarbons (PAHs) and soot platelets. Propargyl radical
addition to but-1-ene-3-yne (vinylacetylene) can start this process, possibly
forming 5-, 6-, and 7-membered rings. A variety of partially intertwined reaction
pathways results from density functional theory (DFT), which indicates three C7H7
radicals, benzyl, tropyl, and vinylcyclopentadienyl, as particularly stable. DFT
energetics forms a basis for a subsequent Rice-Ramsperger-Kassel-Marcus (RRKM)
study at different combustion pressures and temperatures (P = 30-0.01 atm; T =
1200-2400 K). RRKM indicates open-chain structures and 5-rings as the most
important products. Open-chain structures, whose main contributors are the
initial adducts, are favored by lower T and higher P, while 5-rings are favored
by higher T and lower P. The main feature is that the declining yield in open
chain structures with rising T almost mirrors, at all pressures, the growth with
T exhibited by 5-rings (main contributor: fulvenallene). Thus, the two yield
lines for open chains and 5-rings cross at some T, and their crossing moves
toward lower T values as lower P values are considered. Because the T dependence
of the yields (slope of the lines) is more pronounced in the T range close to the
line crossing, it also becomes less pronounced at the lowest P values considered
because the crossing region falls at very low T values. Another constant trait is
that 6-rings (mainly benzyl radical) are the third contributor, though they are
present at most with a modest maximum yield of 2.4-2.7% in a T range which moves
toward lower T as P is reduced.
PMID- 24354453
TI - Differences in features of non-suicidal self-injury according to borderline
personality disorder screening status.
AB - Given that non-suicidal self-injury (NSSI) disorder is being considered for the
upcoming Diagnostic and Statistical Manual of Mental Disorders (DSM-5), it is
important to consider how NSSI occurs with and without borderline personality
disorder (BPD). Participants were 480 undergraduates who completed online
questionnaires and were assigned to 4 groups based on NSSI and BPD status.
Analyses revealed BPD-positive self-injurers had higher self-punishment, anti
suicide, and anti-dissociation functions of NSSI and higher rates of cutting and
burning than BPD-negative self-injurers. Furthermore, difficulty in emotion
regulation, not distress tolerance, was most critical in distinguishing between
groups. Differences between BPD-positive and BPD-negative self-injurers provide
preliminary support for NSSI as a distinct disorder. However, more research in
this area is needed.
PMID- 24354454
TI - High-fluoride toothpaste: a multicenter randomized controlled trial in adults.
AB - OBJECTIVE: The aim of this single - blind, multicenter, parallel, randomized
controlled trial was to evaluate the effectiveness of the application of a high
fluoride toothpaste on root caries in adults. METHODS: Adult patients (n = 130, ?
= 74, ? = 56; mean age +/- SD: 56.9 +/- 12.9) from three participating centers,
diagnosed with root caries, were randomly allocated into two groups: Test (n =
64, ? = 37, ? = 27; lesions = 144; mean age: 59.0 +/- 12.1; intervention: high
fluoride toothpaste with 5000 ppm F), and Control (n = 66, ? = 37, ? = 29;
lesions = 160; mean age: 54.8 +/- 13.5; intervention: regular-fluoride toothpaste
with 1350 ppm F) groups. Clinical examinations and surface hardness scoring of
the carious lesions were performed for each subject at specified time intervals
(T0 - at baseline before intervention, T1 - at 3 months and T2 - at 6 months
after intervention). Mean surface hardness scores (HS) were calculated for each
patient. Statistical analyses comprised of two-way analysis of variance and post
hoc comparisons using the Bonferroni-Dunn correction. RESULTS: At T0 , there was
no statistical difference between the two groups with regard to gender (P =
0.0682, unpaired t-test), or age (P = 0.9786, chi-squared test), and for the
overall HS (Test group: HS = 3.4 +/- 0.61; CONTROL GROUP: HS = 3.4 +/- 0.66; P =
0.8757, unpaired t-test). The anova revealed significantly better HS for the test
group than for the control groups (T1 : Test group: HS = 2.9 +/- 0.67; CONTROL
GROUP: HS = 3.1 +/- 0.75; T2 : Test group: HS = 2.4 +/- 0.81; CONTROL GROUP: HS =
2.8 +/- 0.79; P < 0.0001). However, the interaction term time-point*group was not
significant. CONCLUSIONS: The application of a high-fluoride containing
dentifrice (5000 ppm F) in adults, twice daily, significantly improves the
surface hardness of otherwise untreated root caries lesions when compared with
the use of regular fluoride containing (1350 ppm F) toothpastes.
PMID- 24354455
TI - Challenges and perspectives of Chagas disease: a review.
AB - Chagas disease (CD), also known as American trypanosomiasis, is caused by the
flagellated protozoan Trypanosoma cruzi, and affects an estimated 8 to 10 million
people worldwide. In Latin America, 25 million people live in risk areas, while
in 2008 alone, 10,000 CD-related deaths were reported. This review aimed to
evaluate the challenges of CD control, future perspectives, and actions performed
worldwide to control expansion of the disease and its impact on public health in
Latin America.
PMID- 24354457
TI - Deep-ultraviolet nonlinear optical crystals: Ba3P3O10X (X = Cl, Br).
AB - Deep-ultraviolet nonlinear optical (deep-UV NLO) crystals are of worldwide
interest for the generation of coherent light with wavelength below 200 nm by the
direct second-harmonic generation (SHG) output from solid-state lasers. The
unprecedented deep-UV NLO phosphates representing their own structure types,
Ba3P3O10Cl (BPOC), Ba3P3O10Br (BPOB), have been discovered, which display
moderate powder SHG intensities in type I phase matchable behaviors with a short
UV cutoff edge of 180 nm (measured by a single crystal, one of the shortest
values among phosphates to date). Insightfully, the geometry and polarization of
the C1-P3O10(5-) building unit are affected by the crystal packing. DFT
calculations and cutoff energy dependent SHG coefficient analyses reveal that the
SHG origin is from the cooperation of asymmetric C1-P3O10(5-) anion, Ba(2+)
cation, and Cl(-)/Br(-) anion.
PMID- 24354456
TI - Experimental evidence for ecological selection on genome variation in the wild.
AB - Understanding natural selection's effect on genetic variation is a major goal in
biology, but the genome-scale consequences of contemporary selection are not well
known. In a release and recapture field experiment we transplanted stick insects
to native and novel host plants and directly measured allele frequency changes
within a generation at 186,576 genetic loci. We observed substantial, genome-wide
allele frequency changes during the experiment, most of which could be attributed
to random mortality (genetic drift). However, we also documented that selection
affected multiple genetic loci distributed across the genome, particularly in
transplants to the novel host. Host-associated selection affecting the genome
acted on both a known colour-pattern trait as well as other (unmeasured)
phenotypes. We also found evidence that selection associated with elevation
affected genome variation, although our experiment was not designed to test this.
Our results illustrate how genomic data can identify previously underappreciated
ecological sources and phenotypic targets of selection.
PMID- 24354458
TI - Headaches and hemiparesis in an immunocompetent inmate.
PMID- 24354459
TI - The associations between suicidal ideation and attempt and anxiety symptoms and
the demographic, psychological, and social moderators in Taiwanese adolescents.
AB - The objectives of this study were to examine the associations between suicidal
ideation and attempt and anxiety symptoms and the moderators in 5,027 Taiwanese
adolescents. The associations between suicidal ideation and attempt and anxiety
symptoms on the Taiwanese version of the Multidimensional Anxiety Scale for
Children (MASC-T) were examined using logistic regression analysis. The
moderating effects of demographic (gender and age), psychological (problematic
alcohol use, severe depressive symptoms, and low self-esteem), and social factors
(bullying victimization, and low family function) on the associations were
examined. Adolescents who had anxiety symptoms were more likely to have suicidal
ideation and attempt than those who did not have anxiety symptoms. Bullying
victimization had a moderating effect on the association between suicidal
ideation and anxiety symptoms. Assessment of suicidal ideation and attempt should
be routine practice among adolescents who present with anxiety symptoms.
PMID- 24354460
TI - Pellagra-like condition is xeroderma pigmentosum/Cockayne syndrome complex and
niacin confers clinical benefit.
AB - An extremely rare pellagra-like condition has been described, which was partially
responsive to niacin and associated with a multisystem involvement. The condition
was proposed to represent a novel autosomal recessive entity but the underlying
mutation remained unknown for almost three decades. The objective of this study
was to identify the causal mutation in the pellagra-like condition and
investigate the mechanism by which niacin confers clinical benefit. Autozygosity
mapping and exome sequencing were used to identify the causal mutation, and comet
assay on patient fibroblasts before and after niacin treatment to assess its
effect on DNA damage. We identified a single disease locus that harbors a novel
mutation in ERCC5, thus confirming that the condition is in fact xeroderma
pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the
previously described dermatological response to niacin is consistent with a
dramatic protective effect against ultraviolet-induced DNA damage in patient
fibroblasts conferred by niacin treatment. Our findings show the power of exome
sequencing in reassigning previously described novel clinical entities, and
suggest a mechanism for the dermatological response to niacin in patients with
XP/CS complex. This raises interesting possibilities about the potential
therapeutic use of niacin in XP.
PMID- 24354461
TI - The 5-point Investigator's Global Assessment (IGA) Scale: A modified tool for
evaluating plaque psoriasis severity in clinical trials.
AB - BACKGROUND: To evaluate new psoriasis treatments, clinicians, regulators and
pharmaceutical developers require well-accepted, clinically meaningful measures
of disease severity. The Psoriasis Area and Severity Index (PASI) score is most
widely used as a primary endpoint in clinical trials, although it is not
routinely used in clinical practice. OBJECTIVE: Characterize a 5-point
Investigator's Global Assessment (IGA) tool and evaluate whether it meets the
needs for a valid, clinically meaningful measure. METHODS: A 5-point IGA tool was
developed with input from regulatory authorities and clinical trial investigators
involved with psoriasis drug development and evaluation. Associations between IGA
0/1 responder rates and PASI scores were evaluated using data from two phase 2
studies with the anti-interleukin (IL)-17A monoclonal antibody secukinumab
(AIN457) that utilized a similar 6-point IGA. RESULTS: The 5-point IGA has a more
stringent definition for a score of 1 ("almost clear") compared with 6-point
IGA/Physician's Global Assessment (PGA) tools used in previous trials of other
biologics in moderate-to-severe psoriasis. Whereas IGA/PGA 0/1 responder rates
for earlier scales are strongly associated with PASI 75, the IGA 0/1 rate for the
secukinumab 6-point scale was more robust, demonstrating a strong association
with PASI 90, and the results for the 5-point IGA are expected to show the same
association. DISCUSSION: The 5-point IGA is a valid measure of disease severity
and meets the need for a clinically meaningful measure of success for psoriasis
treatment studies.
PMID- 24354462
TI - Functional and immune response to respiratory syncytial virus infection in aged
BALB/c mice: a search for genes determining disease severity.
AB - BACKGROUND: Recent studies have demonstrated that respiratory syncytial virus
(RSV) is a significant cause of morbidity and mortality in the elderly. The
cellular mechanisms that determine the host's susceptibility and severity of the
disease are not well understood. In this study, we sought a mouse model of human
respiratory disease by studying the functional and cellular response to RSV in
aged animals. METHODS: Aged BALB/c mice (>10 months of age) were infected with
human RSV (strain A2) and compared with sham-infected mice. Clinical progress of
the illness was monitored by daily assessment of weight changes and mortality.
The animals were sacrificed four days postinfection. Lung pathology was obtained
and viral titers were measured by plaque assay. Gene expression profiles were
studied from lung tissue RNA using gene array. RESULTS: RSV produced significant
clinical illness in aged mice as evidenced by a 15% weight loss and a 10%
mortality rate. Lung pathology revealed inflammatory changes with a predominance
of neutrophils and diffuse alveolar damage. Microarray analysis revealed variable
profiles of gene activation/downregulation at day 4 postinfection. RSV infection
resulted in a proinflammatory response. Surprisingly, some of the genes involved
in antigen-processing pathway were downregulated, specifically, genes implicated
in the major histocompatibility complex (MHC) class II pathway. CONCLUSIONS: Our
findings indicate that RSV infection produces profound functional and cellular
changes in aged mice thus resembling the human disease described in the elderly.
Further studies will be needed to understand the cellular mechanisms involved in
the host response to RSV in aged mice.
PMID- 24354463
TI - Quantitative evaluation of myoglobin unfolding in the presence of guanidinium
hydrochloride and ionic liquids in solution.
AB - The use of ionic liquids in biochemical and biophysical applications has
increased dramatically in recent years due to their interesting properties. We
report results of a thermodynamic characterization of the chaotrope-induced
denaturation of equine myoglobin in two different ionic liquid aqueous
environments using a combined absorption/fluorescence spectroscopic approach.
Denaturation by guanidinium hydrochloride was monitored by loss of heme
absorptivity and limited unfolding structural information was obtained from
Forster resonance energy transfer experiments. Results show that myoglobin
unfolding is generally unchanged in the presence of ethylmethylimidazolium
acetate (EMIAc) in aqueous solution up to 150 mM concentration but is facilitated
by butylmethylimidazolium boron tetrafluoride (BMIBF4) in solution. The presence
of 150 mM BMIBF4 alone does not induce unfolding but destabilizes the structure
as observed by a decrease in threshold denaturant concentration for unfolding and
an 80% decrease in the magnitude of DeltaGunfolding from 44 kJ/mol in the absence
of BMIBF4 to 8 kJ/mol in the presence of 150 mM BMIBF4. Thus, the BMIBF4
significantly destabilizes the myoglobin structure while the EMIAc does not,
likely due to differences in anion interaction capabilities. This is confirmed
with control studies using NaAc and LiBF4 solutions. EMIAc may be chosen as
cosolvent additive with minimal effects on protein structure while BMIBF4 may be
used as a supplement in protein folding experiments, potentially allowing access
to proteins which have been traditionally difficult to denature as well as
designing ionic liquids to match protein characteristics.
PMID- 24354464
TI - Correlates of self-care behaviors among low-income elderly women with
hypertension in South Korea.
AB - OBJECTIVE: To identify correlates of self-care behaviors among elderly, low
income Korean women with hypertension. RESEARCH DESIGN: A secondary analysis of
data from a community-based intervention trial for hypertension control. SETTING:
Three community health posts in the Gangwon province, South Korea. PARTICIPANTS:
Two hundred thirty-four (234) low-income elderly women (age 60-93) who had
previously participated in a community-based intervention trial for hypertension
control. METHODS: The researchers collected data that included patient background
characteristics, hypertension self-care behavior, self-efficacy of hypertension
control, general knowledge of hypertension, and social support. The data were
analyzed using descriptive and inferential statistics, including hierarchical
regression analysis. RESULTS: The model explained 41.1% of the total variance in
hypertension self-care behavior scores. Among elderly, low-income Korean women,
the significant factors of their hypertension self-care behavior included: (a)
self-efficacy of hypertension control (beta = .62), (b) social support (beta =
.16), and (c) age (beta = -.14). Hierarchical regression analysis showed that
elderly Korean women that had higher self-efficacy of hypertension control,
higher social support, and were younger were more likely to have higher
hypertension self-care behavior scores. CONCLUSIONS: The results highlight the
need for interventions that focus on improving an individual's self-efficacy and
social support to enhance hypertension self-care. The findings of this study can
help nurses better understand hypertension self-care behavior in elderly, low
income Korean women.
PMID- 24354465
TI - Noninvasive assessment of left atrial phasic function in patients with
hypertension and diabetes using two-dimensional speckle tracking and volumetric
parameters.
AB - OBJECTIVE: To evaluate the left atrial phasic function of hypertensive patients
with or without coexisting diabetes using two-dimensional speckle tracking
echocardiography (2DSTE)-based strain and strain rate imaging and volumetric
parameters. METHODS: The study included an isolated hypertension group (HT group)
comprising 99 patients, a hypertension and diabetes group (HT + DM group)
comprising 65 patients, and 26 age-matched healthy controls. The 2DSTE-based
strain and strain rate images were studied, and the following parameters were
measured: peak left atrial longitudinal strain (LAS-S ), early diastolic (LAS-E )
and late diastolic (LAS-A ) atrial longitudinal strains, and systolic (LASR-S ),
early diastolic (LASR-E ) and late diastolic (LASR-A ) strain rates. RESULTS: The
LAS-S and LASR-S were lower in the HT group and the HT + DM group compared with
the control group (P < 0.001). The LAS-E and LASR-E were lower in the HT group
(14.9 +/- 5.5% and -1.1 +/- 0.4/sec, respectively) than in the control group
(22.1 +/- 8.3% and -1.7 +/- 0.6/sec, respectively) (P < 0.001), and they were
further depressed in the HT + DM group (12.3 +/- 6.3% and -1.0 +/- 0.4/sec,
respectively) (P < 0.05). There were no significant differences in LAS-A or LASR
A among the 3 groups (P > 0.05). Multivariate regression analysis revealed that
HT and DM were independently related to LAS-E and LASR-E . CONCLUSIONS:
Hypertension can lead to abnormal left atrial reservoir and conduit functions,
and coexisting diabetes can further impair conduit function. 2DSTE-derived strain
and strain rate imaging are sensitive methods for evaluating left atrial phasic
function.
PMID- 24354466
TI - Dramatic recovery after severe descending transtentorial herniation-induced Duret
haemorrhage: a case report and review of literature.
AB - BACKGROUND: Although Duret haemorrhage of the brainstem caused by descending
transtentorial herniation is considered fatal, a few cases have been reported to
have good outcome. Moreover, most patients with Duret haemorrhage have severe
primary brain injury and the potential outcome of those with mild primary brain
injury remains unknown. CASE REPORT: This study reports the case of a patient
presenting with Duret haemorrhage caused by an idiopathic subdural haematoma who
demonstrated dramatic recovery. The patient presented with a low Glasgow Coma
Scale score and bilateral oculomotor palsy on admission. Pre-operative CT
revealed a large subdural haematoma and Duret haemorrhage of the mid-brain. The
subdural haematoma was immediately evacuated under local anaesthesia and the
patient demonstrated dramatic post-operative recovery, with no residual
quadriparesis and minimal cognitive dysfunction. Interestingly, only bilateral
oculomotor palsy persisted. This indicates that Duret haemorrhage restricted to
the central portion of the mid-brain without severe primary brain injury has good
prognosis. CONCLUSION: Therefore, patients with Duret haemorrhage of the mid
brain caused by simple subdural haematoma presenting with bilateral oculomotor
palsy, including bilateral pupillary dilation, may not always have a poor
prognosis.
PMID- 24354467
TI - Genome size expansion and the relationship between nuclear DNA content and spore
size in the Asplenium monanthes fern complex (Aspleniaceae).
AB - BACKGROUND: Homosporous ferns are distinctive amongst the land plant lineages for
their high chromosome numbers and enigmatic genomes. Genome size measurements are
an under exploited tool in homosporous ferns and show great potential to provide
an overview of the mechanisms that define genome evolution in these ferns. The
aim of this study is to investigate the evolution of genome size and the
relationship between genome size and spore size within the apomictic Asplenium
monanthes fern complex and related lineages. RESULTS: Comparative analyses to
test for a relationship between spore size and genome size show that they are not
correlated. The data do however provide evidence for marked genome size variation
between species in this group. These results indicate that Asplenium monanthes
has undergone a two-fold expansion in genome size. CONCLUSIONS: Our findings
challenge the widely held assumption that spore size can be used to infer ploidy
levels within apomictic fern complexes. We argue that the observed genome size
variation is likely to have arisen via increases in both chromosome number due to
polyploidy and chromosome size due to amplification of repetitive DNA (e.g.
transposable elements, especially retrotransposons). However, to date the latter
has not been considered to be an important process of genome evolution within
homosporous ferns. We infer that genome evolution, at least in some homosporous
fern lineages, is a more dynamic process than existing studies would suggest.
PMID- 24354468
TI - Snail expression and outcome in T1 high-grade and T2 bladder cancer: a
retrospective immunohistochemical analysis.
AB - BACKGROUND: Neoadjuvant chemotherapy has been shown to have benefit in T1 high
grade or T2 bladder cancer. However, neoadjuvant chemotherapy fails in some
patients. Careful patient selection for neoadjuvant chemotherapy is therefore
needed. Several reports show that Snail is associated with resistance to
chemotherapy. We hypothesized that Snail expression could predict survival in T1
high-grade and T2 bladder cancer patients treated with neoadjuvant chemotherapy.
METHODS: The participants were 44 patients with T1 high-grade and T2 bladder
cancer receiving neoadjuvant chemotherapy. Immunohistochemical analysis was used
to determine Snail expression in specimens of bladder cancer obtained by
transurethral resection before neoadjuvant chemotherapy. The relationships
between Snail expression and patients' outcomes were analyzed. RESULTS: Snail
expression was positive in 15 of the 44 patients (34.1%) and negative in 29
(65.9%). Disease-free survival was significantly shorter for the Snail-positive
group than for the Snail-negative group (p = 0.014). In addition, disease
specific survival was also significantly shorter for the Snail-positive group
than for the Snail-negative group (p = 0.039). In multivariate analysis, Snail
expression level was identified as an independent prognostic factor for disease
specific survival (p = 0.020). CONCLUSIONS: The results indicate that Snail
expression may predict poor outcome in T1 high-grade and T2 bladder cancer
patients treated with neoadjuvant chemotherapy.
PMID- 24354469
TI - Comprehensive multiphase NMR spectroscopy of intact 13C-labeled seeds.
AB - Seeds are complex entities composed of liquids, gels, and solids. NMR
spectroscopy is a powerful tool for studying molecular structure but has evolved
into two fields, solution and solid state. Comprehensive multiphase (CMP) NMR
spectroscopy is capable of liquid-, gel-, and solid-state experiments for
studying intact samples where all organic components are studied and
differentiated in situ. Herein, intact (13)C-labeled seeds were studied by a
variety of 1D/2D (1)H/(13)C experiments. In the mobile phase, an assortment of
metabolites in a single (13)C-labeled wheat seed were identified; the gel phase
was dominated by triacylglycerides; the semisolid phase was composed largely of
carbohydrate biopolymers, and the solid phase was greatly influenced by starchy
endosperm signals. Subsequently, the seeds were compared and relative
similarities and differences between seed types discussed. This study represents
the first application of CMP-NMR to food chemistry and demonstrates its general
utility and feasibility for studying intact heterogeneous samples.
PMID- 24354470
TI - The physician-patient working alliance and patient psychological attachment,
adherence, outcome expectations, and satisfaction in a sample of rheumatology
patients.
AB - Over the past twenty years, the physician-patient relationship (eg, the physician
patient working alliance) has emerged as an integral component to the treatment
of patients for a myriad of health conditions. Psychological, emotional, and
behavioral dimensions of patients' working alliance with their physicians, along
with patients' attachment styles, were examined in relation to rheumatology
patients' adherence to treatment plans, outcome expectations, and satisfaction.
Study participants were 101 adult outpatients from a rheumatology clinic. Path
analyses demonstrated that the physician-patient working alliance predicted
outcome expectations (Standardized Beta [SB] = 0.27), and patient satisfaction
(SB = 0.62), and that patient satisfaction in turn predicted patient adherence
(SB = 0.48). Physicians' ratings of patient adherence were significantly and
positively correlated with patients' ratings of the physician-patient working
alliance. No significant paths were evident with respect to patient attachment.
The physician-patient working alliance directly predicts patient satisfaction,
and outcome expectations, and indirectly predicts adherence through patient
satisfaction.
PMID- 24354471
TI - Wound care practices: a survey of acute care nurses.
AB - AIMS AND OBJECTIVES: To describe the self-reported wound care practices of acute
care nurses practising in a large metropolitan hospital in Queensland, Australia.
BACKGROUND: Wound infections occur in up to 30% of surgical procedures and are
the third most commonly reported hospital-acquired infection. The growing
complexity and cost of wound care demand that nurses use wound care knowledge
based on best practice guidelines. DESIGN: Descriptive cross-sectional survey
design. METHODS: A convenience sample of 250 medical and surgical nurses working
in an acute care facility was invited to complete a 42-item survey. The survey
was based on an extensive literature review and an environmental scan of wound
care issues in major hospitals, Australia. RESULTS: The survey was completed by
120 acute care nurses with a response rate of 48%. Ninety (75.6%) respondents
reported that 'wound appearance' was the most important factor guiding their
choice of dressing product. Only 6 (5.0%) respondents considered the cost of a
dressing product 'highly important'. Fifty-nine (50.4%) respondents reported
being 'unaware' of the national standards pertaining to wound management, and
only 41 (34.7%) respondents reported that their knowledge of wound products was
'good' or 'excellent'. The majority (n = 89, 75.4%) of respondents used the
hospital's wound care specialist nurses as the primary source of information in
regard to managing acute wounds. CONCLUSIONS: Although acute care nurses have a
sound knowledge of wound healing processes, it appears that many do not use the
recommended clinical guideline pertaining to wound care. RELEVANCE TO CLINICAL
PRACTICE: While it is important for nurses to detect early wound complications,
treatment plans based on wound assessments need to be informed by current
clinical guidelines. In implementing the guideline, it is essential to first
identify barriers and facilitators to knowledge transfer.
PMID- 24354472
TI - Identification of Wnt/beta-catenin signaling pathway in dermal papilla cells of
human scalp hair follicles: TCF4 regulates the proliferation and secretory
activity of dermal papilla cell.
AB - It is clear that the dermal papilla cell (DPC), which is located at the bottom of
the hair follicle, is a special mesenchymal component, and it plays a leading
role in regulating hair follicle development and periodic regeneration. Recent
studies showed that the Wnt signaling pathway through beta-catenin (canonical Wnt
signaling pathway) is an essential component in maintaining the hair-inducing
activity of the dermal papilla and growth of hair papilla cells. However, the
intrinsic pathways and regulating mechanism are largely unknown. In the previous
work, we constructed a cDNA subtractive library of DPC and first found that the
TCF4 gene, as a key factor of Wnt signaling pathway, was expressed as the
upregulated gene of the hair follicle in low-passage DPC. This study was to
explore the role of TCF4 in regulating the proliferation and secretory activity
of DPC. We constructed a pcDNA3.0-TCF4 expression vector and transfected it into
DPC to achieve stable expression by bangosome 2000. Furthermore, we used the
method of chemosynthesis to synthesize three pairs of TCF4 siRNA and transfected
them into DPC. Meanwhile, we compared the transfection group and non-transfection
group. We first proposed that there was expression difference in TCF4 in DPC
under different biological condition. This study may have a high impact on the
molecular mechanism of follicular lesions and provide a new vision for the
treatment of clinic diseases.
PMID- 24354473
TI - Management of temporomandibular joint arthritis-related orofacial symptoms in
juvenile idiopathic arthritis by the use of a stabilization splint.
AB - OBJECTIVES: Temporomandibular joint (TMJ) inflammation in patients with juvenile
idiopathic arthritis (JIA) may interfere with optimal joint and muscle function.
Orofacial symptoms are common findings in relation to TMJ arthritis. Previous
research on management of TMJ arthritis-related orofacial symptoms in patients
with JIA has focused on pharmacological treatment modalities without involving
physical pain management strategies. The aim of this study was to evaluate
changes in orofacial pain and TMJ function after stabilization splint treatment.
METHOD: Twenty-eight consecutive patients with JIA and arthritis-related
orofacial symptoms (mean age 15.5 years, range 8.2-25 years) were included in
this prospective observational study. All patients received stabilization splint
treatment. A comparable group of 110 healthy children served as controls for the
assessments of TMJ mobility. RESULTS: After splint treatment for 8 weeks, a
significant reduction in orofacial pain frequency and intensity was reported, and
significant improvement in TMJ function was observed. However, TMJ mobility at
follow-up remained significantly reduced when compared to the control group.
CONCLUSIONS: The stabilization splint is a safe, reversible, low-cost treatment,
and familiar to most dental practitioners. Based on our findings, we propose the
implementation of stabilization splint therapy for the treatment of JIA patients
with TMJ arthritis-related symptoms.
PMID- 24354474
TI - FDG-PET in healthy and epileptic Lagotto Romagnolo dogs and changes in brain
glucose uptake with age.
AB - Regional cerebral metabolism and blood flow can be measured noninvasively with
positron emission tomography (PET). 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)
widely serves as a PET tracer in human patients with epilepsy to identify the
seizure focus. The goal of this prospective study was to determine whether
juvenile or adult dogs with focal-onset epilepsy exhibit abnormal cerebral
glucose uptake interictally and whether glucose uptake changes with age. We used
FDG-PET to examine six Lagotto Romagnolo dogs with juvenile epilepsy, two dogs
with adult-onset epilepsy, and five control dogs of the same breed at different
ages. Three researchers unaware of dog clinical status visually analyzed co
registered PET and magnetic resonance imaging (MRI) images. Results of the visual
PET analyses were compared with electroencephalography (EEG) results. In
semiquantitative analysis, relative standard uptake values (SUV) of regions of
interest (ROI) drawn to different brain regions were compared between epileptic
and control dogs. Visual analysis revealed areas of hypometabolism interictally
in five out of six dogs with juvenile epilepsy in the occipital, temporal, and
parietal cortex. Changes in EEG occurred in three of these dogs in the same areas
where PET showed cortical hypometabolism. Visual analysis showed no abnormalities
in cerebral glucose uptake in dogs with adult-onset epilepsy. Semiquantitative
analysis detected no differences between epileptic and control dogs. This result
emphasizes the importance of visual analysis in FDG-PET studies of epileptic
dogs. A change in glucose uptake was also detected with age. Glucose uptake
values increased between dog ages of 8 and 28 weeks and then remained constant.
PMID- 24354475
TI - Hizikia fusiformis fractions successfully improve atopic dermatitis indices in
anti-CD3-stimulated splenocytes and 2,4-dinitrochlorobenzene-treated BALB/c mice.
AB - OBJECTIVES: In the present study, we aimed to examine whether fractions from an
edible sea weed, Hizikia fusiformis, had immunomodulatory effects, particularly
an anti-atopic effect, by attenuating the expression of T cell-dependent
cytokines using in-vitro and in-vivo animal atopic dermatitis-like models.
METHODS: The anti-atopic activities were examined in in vitro, and a 2,4
dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like mouse model using
quantitative real-time polymerase chain reaction, electrophoretic-mobility shift
and histopathological analysis. KEY FINDINGS: Our results showed that the final
fraction (F2') of H. fusiformis contained a higher amount of butanoic acid which
was not found in the other fractions, and effectively inhibited T cell activation
by inhibiting dephosphorylation of nuclear factor of activated T cells in
electrophoretic-mobility shift assay. As a consequence, helper T cell-dependent
cytokines, such as interleukin-2, -4 and interferon-gamma, were significantly
inhibited while activated with an anti-CD3 antibody. We also showed that skin
challenged with DNCB successfully recovered when treated with 2.5 mg/kg,
comparable to that by 0.25% prednicarbate. These results indicate that F2' may
contribute to inhibit T cell activation by eliminating Th cell-dependent
cytokines. CONCLUSIONS: Taken together, we concluded that F2' containing butanoic
acid may be a new functional anti-atopic candidate, which probably acts through
nuclear factor of activated T cell inactivation mechanisms.
PMID- 24354476
TI - A crossover pilot study evaluating the functional outcomes of two different types
of robotic movement training in chronic stroke survivors using the arm
exoskeleton BONES.
AB - BACKGROUND: To date, the limited degrees of freedom (DOF) of most robotic
training devices hinders them from providing functional training following
stroke. We developed a 6-DOF exoskeleton ("BONES") that allows movement of the
upper limb to assist in rehabilitation. The objectives of this pilot study were
to evaluate the impact of training with BONES on function of the affected upper
limb, and to assess whether multijoint functional robotic training would
translate into greater gains in arm function than single joint robotic training
also conducted with BONES. METHODS: Twenty subjects with mild to moderate chronic
stroke participated in this crossover study. Each subject experienced multijoint
functional training and single joint training three sessions per week, for four
weeks, with the order of presentation randomized. The primary outcome measure was
the change in Box and Block Test (BBT). The secondary outcome measures were the
changes in Fugl-Meyer Arm Motor Scale (FMA), Wolf Motor Function Test (WMFT),
Motor Activity Log (MAL), and quantitative measures of strength and speed of
reaching. These measures were assessed at baseline, after each training period,
and at a 3-month follow-up evaluation session. RESULTS: Training with the robotic
exoskeleton resulted in significant improvements in the BBT, FMA, WMFT, MAL,
shoulder and elbow strength, and reaching speed (p < 0.05); these improvements
were sustained at the 3 month follow-up. When comparing the effect of type of
training on the gains obtained, no significant difference was noted between
multijoint functional and single joint robotic training programs. However, for
the BBT, WMFT and MAL, inequality of carryover effects were noted; subsequent
analysis on the change in score between the baseline and first period of training
again revealed no difference in the gains obtained between the types of training.
CONCLUSIONS: Training with the 6 DOF arm exoskeleton improved motor function
after chronic stroke, challenging the idea that robotic therapy is only useful
for impairment reduction. The pilot results presented here also suggest that
multijoint functional robotic training is not decisively superior to single joint
robotic training. This challenges the idea that functionally-oriented games
during training is a key element for improving behavioral outcomes. TRIAL
REGISTRATION: NCT01050231.
PMID- 24354477
TI - 4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through
PI3K/Akt/mTOR-independent pathway.
AB - Drug resistance is one of the most formidable obstacles for treatment of glioma.
Eukaryotic initiation factor 4E-binding protein (4E-BP1), a key component in the
rate-limiting step of protein translation initiation, is closely associated with
poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is
involved in the drug resistance of human glioma. Herein we show that the
expression of 4E-BP1 in human SWOZ2-BCNU drug-resistant glioma cells is
significantly lower than that of the parent SWOZ2 cell line. Moreover, down
regulation of 4E-BP1 by short interfering RNA significantly impaired the
sensitivity of SWOZ2 and U251 cells to carmustine (BCNU). Furthermore,
overexpression of 4E-BP1 with plasmid transfection regained this sensitivity.
Clinical studies showed that the expression levels of 4E-BP1 in primary glioma
tissues were markedly higher than those of recrudescent glioma tissues. Taken
together, our results suggest that 4E-BP1 is a novel protein that contributes to
acquired drug resistance and it may be a potential target for reversing drug
resistance in human glioma.
PMID- 24354478
TI - Complete resolution of idiopathic sclerosing orbital inflammation after treatment
with rituximab.
PMID- 24354479
TI - Long-standing prophylactic therapy vs. episodic treatment in young people with
severe haemophilia: a comparison of age-matched Danish and Russian patients.
AB - Two distinctly different substitution principles are commonly used in
haemophilia: treatment at bleeding episodes only referred to as on-demand
treatment, and prophylactic factor administration. The aim of the cross-sectional
study which was undertaken in young patients suffering severe haemophilia A was
to challenge our hypothesis that on-demand treatment is inferior to prophylactic
substitution in prevention of chronic joint disease at young age. The method
involved an investigation of 40 patients from Russia (n = 27) and Denmark (n =
13) born between 1975 and 1990 with no history of inhibitors; Russian patients
had exclusively received factor VIII on demand, while Danish patients were
managed with prophylactic treatment during a mean period of 16 years since median
age of 5 years. The study endpoints were clinical joint scores, Quality of Life
scores and functional independence scores. Matched by identical age (+/-1 year)
13 Danish and 13 Russian patients were compared, while 14 age similar Russian
patients served as controls. Demographic data among all groups were quite
comparable. The results are that Russian patients presented with clinical joint
scores at 27 +/- 8.5 (mean +/- SD) while matched Danish counterparts scored 3.8
+/- 5.3 (mean +/- SD), differences being highly significant. The number of joint
bleeds in recent 5 years were 199.5 +/- 135 (mean +/- SD) vs. 8.1 +/- 8.7 (mean
+/- SD). Likewise, Quality of Life and functional independence scores were
significantly higher in patients on prophylaxis as compared to on-demand
treatment. In conclusion, the study outcomes confirmed our hypothesis. Longer
term prophylactic factor administration during childhood and adolescence prevents
joint destruction.
PMID- 24354481
TI - Acquired factor XIII deficiency: still a clinical challenge in the era of novel
therapy.
PMID- 24354480
TI - Primary and rescue immune tolerance induction in children and adults: a
multicentre international study with a VWF-containing plasma-derived FVIII
concentrate.
AB - Most studies on immune tolerance induction (ITI) therapy in haemophilia A
patients are focused on primary ITI in children. Here we report on the ITI
outcome in a large retrospective cohort, including adults and patients with
rescue ITI, treated with a pdFVIII/VWF concentrate. Retrospective data from
haemophilic patients (FVIII< 2%) with inhibitors from 22 centres in Spain, Italy
and Germany, who underwent primary or rescue ITI with pdFVIII/VWF concentrate,
were collected. Complete success (CS), partial success (PS) and failure were
defined based on the criteria of the consensus recommendations of the 2006
International ITI Workshop. A total of 41 cases of primary ITI (32 children and 9
adults) and 19 cases of rescue ITI (17 children and 2 adults) were evaluated.
Success (CS+PS) rate of 87% was achieved in primary ITI and 74% in the higher
risk profile of rescue ITI. Eight of nine (85%) patients with poorest prognosis
(three or more of the known risk factors of poor response to ITI) achieved
success (CS+PS). CS of 100% was observed in eight primary ITI patients with titre
at start of ITI <=2.5 BU and inhibitor peak <=25 BU. The favourable response
rates in primary and rescue ITI in children and in adult patients, even in the
presence of poor prognostic factors, should be encouraged for broadening the
indication of immune tolerance therapy in haemophilia A patients with inhibitors.
PMID- 24354482
TI - End-stage haemophilic arthropathy of the ankle: ankle fusion or total ankle
replacement.
PMID- 24354483
TI - Continuous infusion of rFVIIa during surgery in a FVII-deficient patient: a case
report from Japan.
PMID- 24354484
TI - Safety of recombinant activated factor VII (rFVIIa) in patients with congenital
haemophilia with inhibitors: overall rFVIIa exposure and intervals following high
(>240 MUg kg-1) rFVIIa doses across clinical trials and registries.
AB - Recombinant activated factor VII (rFVIIa) is indicated for treatment of bleeding
in congenital haemophilia with inhibitors (CHwI) using 90 MUg kg(-1) every 2-3 h
(EU and US) or a single 270 MUg kg(-1) dose (EU only) with ~90% efficacy reported
for both regimens. Dosing of rFVIIa varies, and home treatment makes assessment
of frequency of doses >90 MUg kg(-1), the intervals before additional treatment,
and the risk for thromboembolic events (TEs) more difficult. This post hoc
analysis assessed the safety and distribution of rFVIIa dosing in CHwI and the
impact of >240 MUg kg(-1) dosing on subsequent bypassing agent (BPA) dosing
interval and frequency. Data regarding on-demand or prophylactic rFVIIa dosing,
TE incidence and subsequent BPA dosing after high rFVIIa doses were compiled from
multiple sources incorporating safety surveillance. A total of 61 734 rFVIIa
doses were reported in 481 patients treated for 3947 bleeds and for 43 135
prophylaxis days. Over half (52%) exceeded 120 MUg kg(-1), 37% exceeded 160 MUg
kg(-1) and 15% exceeded 240 MUg kg(-1). Subsequent doses of BPA(s) were
administered after 38% of initial and 49% of any rFVIIa dose >240 MUg kg(-1), and
were most frequently administered >=24 h after initial (40%) or any (53%) doses
>240 MUg kg(-1). No TEs were reported. The findings of this analysis show that
rFVIIa doses >90 MUg kg(-1) are utilized for 'real-world' treatment of children
and adults. When additional BPA was administered following an rFVIIa dose >240
MUg kg(-1), reported intervals were prolonged, often >=24 h. No safety issues
were identified in the 61,734 doses analysed.
PMID- 24354485
TI - Production of functional coagulation factor VIII from iPSCs using a lentiviral
vector.
AB - The use of induced pluripotent stem cells (iPSCs) as an autologous cell source
has shed new light on cell replacement therapy with respect to the treatment of
numerous hereditary disorders. We focused on the use of iPSCs for cell-based
therapy of haemophilia. We generated iPSCs from mesenchymal stem cells that had
been isolated from C57BL/6 mice. The mouse iPSCs were generated through the
induction of four transcription factor genes Oct3/4, Klf-4, Sox-2 and c-Myc. The
derived iPSCs released functional coagulation factor VIII (FVIII) following
transduction with a simian immunodeficiency virus vector. The subcutaneous
transplantation of iPSCs expressing FVIII into nude mice resulted in teratoma
formation, and significantly increased plasma levels of FVIII. The plasma
concentration of FVIII was at levels appropriate for human therapy at 2-4 weeks
post transplantation. Our data suggest that iPSCs could be an attractive and
prospective autologous cell source for the production of coagulation factor, and
that engineered iPSCs expressing coagulation factor might provide a cell-based
therapeutic strategy appropriate for haemophilia.
PMID- 24354486
TI - Clinical features and management of haemophilic pseudotumours: a single US centre
experience over a 30-year period.
AB - Given the rarity of haemophilic pseudotumours, consensus on management is
lacking. We describe the clinical features and management of haemophilic
pseudotumours by retrospectively reviewing the medical records of haemophilia
patients with a diagnosis of pseudotumour seen at our Hemophilia Center from 1981
to 2011. We recorded the following data: type and severity of haemophilia,
documented aetiological antecedent, localization of the pseudotumour, presenting
symptoms, management and outcome. We identified 12 pseudotumours in 11 patients
over a 30-year period. Six patients had known inhibitors or a history of
inhibitor. An aetiological antecedent leading to the development of pseudotumour
was reported in nine cases. Localization of the pseudotumour was confined to soft
tissue (n = 3) and bone (n = 8). Six of the 12 pseudotumours (50%) were not
diagnosed at the time of initial presentation, with a delay ranging from 6 weeks
to 6 years. In eight cases, surgical intervention (surgical drainage, n = 2;
excision, n = 4; limb amputation, n = 2) was the initial treatment choice, with
complete resolution in six cases. Conservative management with close monitoring
occurred in three cases, with one case subsequently requiring surgical resection.
We conclude that haemophilic pseudotumours still occur sporadically, and the
diagnosis is frequently delayed. Surgical intervention is generally a safe and
effective treatment, although conservative management may be appropriate in
selected cases.
PMID- 24354487
TI - Musculoskeletal evaluation in severe haemophilia A patients from Latin America.
AB - There is a paucity of literature on haemophilia treatment in Latin American
countries, a region characterized by rapidly improving systems of care, but with
substantial disparities in treatment between countries. The aim of this study was
to evaluate the musculoskeletal status of haemophilia patients from Latin America
and to examine the relationship between musculoskeletal status and treatment
practices across countries. The Committee of Latin America on the Therapeutics of
Inhibitor Groups conducted a survey of its member country representatives on key
aspects of haemophilia treatment in 10 countries. Musculoskeletal status of
patients was obtained during routine comprehensive evaluations between March 2009
and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%)
without inhibitors (<0.6 BU mL(-1) ) and were >=5 years of age. Musculoskeletal
status was compared between three groups of countries, based primarily on
differences in the availability of long-term prophylaxis. Overall, 143 patients
(5-66 years of age) were enrolled from nine countries. In countries where long
term prophylaxis had been available for at least 10 years (Group A), patients
aged 5-10 years had significantly better mean World Federation of Hemophilia
clinical scores, fewer target joints and fewer affected joints than patients from
countries where long-term prophylaxis has been available for about 5 years (Group
B) or was not available (Group C). In Latin America, the musculoskeletal status
of patients with severe haemophilia without inhibitors has improved significantly
in association with the provision of long-term prophylaxis. As more countries in
Latin America institute this practice, further improvements are anticipated.
PMID- 24354488
TI - Thrombin generation as objective parameter of treatment response in patients with
severe haemophilia A and high-titre inhibitors.
AB - In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies
in response to replacement therapy with factor VIII (FVIII), requiring bypass
therapy such as activated prothrombin complex concentrate (APCC). Because bypass
therapy has not been broadly available in Mexico even in recent years, this study
aimed to evaluate the thrombin generation assay (TGA) in assessing the response
to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We
studied 189 patients with severe HA. Clinical severity was verified by one-stage
APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen
Bethesda (N-B) method, and type of inhibition was assessed through serial plasma
dilutions. Thrombin generation was measured with the calibrated automated
thrombogram in inhibitor-positive plasmas previously spiked and incubated with
FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests.
We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25
(13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We
found an association between kinetic behaviour and clinical response to FVIII (P
= 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global
concordance between clinical and in vitro response was 70%. By evaluating the
capacity of thrombin formation in a plasma sample, TGA predicts the response to
FVIII or APCC therapy and allows individual optimization of resources in patients
with severe HA and high-titre inhibitors. The inhibition pattern of the
antibodies to FVIII:C correlated with the TGA parameters and showed an
association with the clinical response to FVIII.
PMID- 24354489
TI - Polymorphism of thrombin-activatable fibrinolysis inhibitor and risk of
intracranial haemorrhage in factor XIII deficiency.
PMID- 24354490
TI - A Bayesian approach to the analysis of quantal bioassay studies using
nonparametric mixture models.
AB - We develop a Bayesian nonparametric mixture modeling framework for quantal
bioassay settings. The approach is built upon modeling dose-dependent response
distributions. We adopt a structured nonparametric prior mixture model, which
induces a monotonicity restriction for the dose-response curve. Particular
emphasis is placed on the key risk assessment goal of calibration for the dose
level that corresponds to a specified response. The proposed methodology yields
flexible inference for the dose-response relationship as well as for other
inferential objectives, as illustrated with two data sets from the literature.
PMID- 24354491
TI - Differential expressions of stromal cell-derived factor-1alpha and vascular
endothelial growth factor in the placental bed of pregnancies complicated by
preeclampsia.
AB - OBJECTIVE: The aim of this study is to examine the differential expression of
stromal cell-derived factor-1alpha (SDF-1alpha)/CXCR4 and vascular endothelial
growth factor (VEGF) in the third trimester placental bed of normotensive
controls and preeclamptic patients. METHODS: Placental bed tissues were collected
from 15 patients with preeclampsia (PE) and 15 gestational-matched normotensive
controls at the time of their cesarean delivery. Placental bed expressions of SDF
1alpha, CXCR4 and VEGF were evaluated by reverse transcriptase-polymerase chain
reaction (RT-PCR), real-time PCR and immunohistochemical staining. RESULTS: No
statistical difference was found between the PE and the normotensive control
group with respect to their age and parity, gravidity and body mass index. The
placental bed expressions of SDF-1alpha/CXCR4 and VEGF were significantly
decreased in the PE group compared with the normotensive control group.
CONCLUSIONS: This study showed decreased expressions of SDF-1alpha/CXCR4 and VEGF
in the third trimester placental bed of pregnancies with PE. This result suggests
that decreased expressions of SDF-1alpha/CXCR4 and VEGF in the placental bed
could be associated with the pathogenesis of PE.
PMID- 24354492
TI - Activation of gas-phase uranyl: from an oxo to a nitrido complex.
AB - The uranyl moiety, UO2(2+), is ubiquitous in the chemistry of uranium, the most
prevalent actinide. Replacing the strong uranium-oxygen bonds in uranyl with
other ligands is very challenging, having met with only limited success. We
report here uranyl oxo bond activation in the gas phase to form a terminal
nitrido complex, a previously elusive transformation. Collision induced
dissociation of gas-phase UO2(NCO)Cl2(-) in an ion trap produced the nitrido oxo
complex, NUOCl2(-), and CO2. NUOCl2(-) was computed by DFT to have Cs symmetry
and a singlet ground state. The computed bond length and order indicate a triple
U-N bond. Endothermic activation of UO2(NCO)Cl2(-) to produce NUOCl2(-) and
neutral CO2 was computed to be thermodynamically more favorable than NCO ligand
loss. Complete reaction pathways for the CO2 elimination process were computed at
the DFT level.
PMID- 24354493
TI - No correlation between initial arterial carboxyhemoglobin level and degree of
lung injury following ovine burn and smoke inhalation.
AB - Fire victims often suffer from burn injury and concomitant inhalation trauma, the
latter significantly contributing to the morbidity and mortality in these
patients. Measurement of blood carboxyhemoglobin levels has been proposed as a
diagnostic marker to verify and, perhaps, quantify the degree of lung injury
following inhalation trauma. However, this correlation has not yet been
sufficiently validated. A total of 77 chronically instrumented sheep received
sham injury, smoke inhalation injury, or combined burn and inhalation trauma
following an established protocol. Arterial carboxyhemoglobin concentrations were
determined directly after injury and correlated to several clinical and
histopathological determinants of lung injury that were detected 48 hours post
injury. The injury induced severe impairment of pulmonary gas exchange and
increases in transvascular fluid flux, lung water content, and airway obstruction
scores. No significant correlations were detected between initial
carboxyhemoglobin levels and all measured clinical and histopathological
determinants of lung injury. In conclusion, the amount of arterial
carboxyhemoglobin concentration cannot predict the degree of lung injury at 48
hours after ovine burn and smoke inhalation trauma.
PMID- 24354494
TI - A unique heterogeneous nucleophilic catalyst comprising methylated nitrogen
substituted porous silica provides high product selectivity for the Morita-Baylis
Hillman reaction.
AB - Methylated nitrogen-substituted microporous and mesoporous silica exhibited
almost the same catalytic performance as that of a conventional homogeneous base
catalyst. They also demonstrated unexpectedly high product selectivity for the
Morita-Baylis-Hillman reaction of formaldehyde with methyl acrylate at high
temperatures.
PMID- 24354495
TI - Development of the MMPI-2 cognitive complaints scale as an embedded measure of
symptom validity.
AB - OBJECTIVE: To empirically-derive a new MMPI-2 sub-scale, the 13-item Cognitive
Complaints Scale (CCS), as an embedded measure of symptom validity. This study
hypothesized that mild traumatic brain injured subjects with financial incentives
who failed performance validity tests (PVTs) would score significantly higher on
the CCS compared to mild traumatic brain injured subjects with financial
incentives who passed PVTs. Mild traumatic brain injured controls with no
financial incentives were predicted to score lowest on the CCS. RESEARCH DESIGN:
A known groups design was utilized as this design allows for the accurate
classification of criterion groups. METHODS: One hundred and fifty mild head
injured adults were assigned to one of three groups: the Failed Performance
Validity (FPV) group, the Passed Performance Validity (PPV) group or a control
group. RESULTS: An ANOVA revealed that the FPV group scored significantly higher
on the CCS compared to the PPV group. Controls with no financial incentives
scored lowest. A CCS cut-score of >=12 discriminated between the FPV and PPV
groups at a high level of specificity (94%). CONCLUSIONS: A dissociation between
'performance validity' and 'symptom validity' supports recommendations for the
differential application of these descriptive terms. The CCS may be helpful to
assess credibility of clinical presentation in situations where PVTs are absent.
PMID- 24354497
TI - Challenging historical perspectives of the 24-h chemotherapy day: Flexible
chemotherapy dose-timing guidelines.
AB - AIM: Variation in dose-timing within multiday chemotherapy regimens is largely
unknown with convention being to administer subsequent days of treatment at 24-h
intervals. However, in reality there are many occasions where doses are given
either earlier or later to accommodate a variety of clinical and operational
priorities. This project aimed to evaluate the degree of existing variation in
chemotherapy dose-timing and to investigate whether deliberate variation could
improve quality and efficiency outcomes such as reduction of after hours
chemotherapy administration or reduced inpatient length of stay. METHOD:
Chemotherapy charts and hospital admission datasets (n = 112) from sarcoma and
hematology inpatient regimens were retrospectively audited to ascertain existing
variation in dose-timing and overall length of stay. Clinical practice guidelines
enabling a safe degree of dose-timing variation for individual chemotherapy
regimens were developed, implemented over a 3-month period, and evaluated against
safety, efficiency and economic outcomes. RESULTS: Baseline dose-timing variation
was common with administration occurring up to 8 h early and 7 h later than
conventional 24-h dosing intervals. Following implementation of clinical practice
guidelines, there was a 10% reduction in chemotherapy finishing after hours and a
significant reduction in length of stay for two sarcoma regimens, projected to
save 24 inpatient bed days (over $20,000) across more than forty inpatient
episodes annually. CONCLUSION: Deviation from the standard 24-h chemotherapy day
(deliberately or inadvertently) was a common yet unstandardized practice.
Clinical practice guidelines enabling flexible dose-timing of chemotherapy
provided an opportunity to improve chemotherapy administration safety measures,
tailor chemotherapy delivery to ward and patient needs, and in some instances
reduce non-value-added length of stay.
PMID- 24354496
TI - Relevance of seminal plasma nitric oxide levels and the efficacy of SSRI
treatment on lifelong premature ejaculation.
AB - The aim of this study was to determine the relevance of seminal plasma nitric
oxide (NO) levels and the efficacy of selective serotonin reuptake inhibitor
(SSRI) treatment on premature ejaculation. A total of 16 men (aged 32.18 +/-
3.32) with lifelong premature ejaculation [intravaginal ejaculation latency time
(IELT) <1 min] and 11 healthy men (control group) were included in this study.
The healthy men formed Group 1, and the patients were randomly categorised into
two groups. Group 2 patients received 20 mg day(-1) of paroxetine, and Group 3
patients received 50 mg day(-1) of sertraline for 4 weeks. Baseline and post
treatment findings were compared among the three groups. Mean baseline seminal NO
levels in men with premature ejaculation were significantly higher than in the
healthy control group (32.24 +/- 5.61 MUm l(-1) versus 19.71 +/- 3.50 MUm l(-1) ,
respectively) (P < 0.001). There was no significant difference between the
sertraline and paroxetine groups in terms of IIEF scores, IELT scores and NO
levels. At the end of the first month, the mean IELT scores of the paroxetine and
sertraline groups showed a significant improvement compared with the baseline
values (P < 0.001). After treatment with paroxetine and sertraline, NO levels dec
reased from baseline. Our study indicates that premature ejaculation is
significantly related with a higher level of seminal NO. Baseline seminal plasma
NO values obtained in patients with premature ejaculation were significantly
higher than in the healthy control group. After treatment with SSRIs, decreased
seminal NO may retard ejaculation. Further studies are needed to confirm this
suggestion and the role of NO in the pathophysiology and treatment of premature
ejaculation.
PMID- 24354498
TI - The Interprofessional Psychosocial Oncology Distance Education (IPODE) project:
perceived outcomes of an approach to healthcare professional education.
AB - The Interprofessional Psychosocial Oncology Distance Education (IPODE) project
was designed as an approach to the problems of feasibility and accessibility in
specialty health professional education, in this case, psychosocial oncology
(PSO). In this article, we report the evaluation findings from the first three
years of the project in relation to one IPODE course, which was offered as a
graduate level university elective in nine Canadian universities and as a
continuing education (CE) option to health professionals between January 2008 and
May 2010. The evaluation included a pre and post questionnaire that explored how
an interprofessional (IP), web-based, PSO course influenced participants'
knowledge, attitudes and beliefs about IP, person-centered PSO care. It also
examined what attributes of a web-based platform were most effective in
delivering an IP PSO course. The study yielded two key findings. First, web-based
learning in a pan-Canadian and cross-university collaboration is a viable
alternative to providing specialty education and significantly improves
knowledge, attitudes and beliefs about IP, person-centered PSO care. Second, a
web-based platform with real-time seminars, discussion boards and multiple audio
visual resources that privilege first person illness narratives were important
elements in expanding knowledge and shifting attitudes about IP practice and
person-centered care in regards to PSO. In their evaluation, course participants
highlighted a variety of ways in which the course expanded their vision about
what constitutes an IP team and increased their confidence in interacting with
healthcare professionals from professions other than their own.
PMID- 24354499
TI - The making of the interprofessional arena in the United Kingdom: a social and
political history.
AB - This article offers a critical sociological rendering of the making of the
interprofessional arena in the United Kingdom. It offers an interpretation of the
conditions that led to the formation, expansion and development of the
interprofessional arena using a social worlds/arenas lens of secondary data. I
propose that the making of the interprofessional arena has been achieved in three
historiographical phases. First, the "recognition of the professionalisation
conundrum" that led to the intuitive assumption that interprofessional education
(IPE) could lead to improved collaboration in practice and improved outcomes.
Second, the "legitimisation" of the interprofessional assumption through the
development of networks, building consensus, nurturing an evidence base and
negotiating with policymakers. Third, "Talking up and acting up" the
interprofessional agenda by developing global communities of practice, pandering
to a neoliberal agenda, disseminating exemplars of good practice and encouraging
practical changes within diverse settings. Articulating these historical
"moments" may allow us insights into the conditions that have created the
contemporary interprofessional arena and offer us ways of considering how present
conditions may re-shape the discourses that constitute the interprofessional
arena of the future.
PMID- 24354500
TI - The effect of postinjury depression on quality of life following minor injury.
AB - PURPOSE: To describe quality of life (QoL) in the year following minor injury and
to test the hypothesis that individuals with depression in the postinjury year
experience lower QoL than do individuals with no depression. DESIGN: Prospective,
longitudinal, cohort design. A total of 275 adults were randomly selected from
injured patients presenting to an urban emergency department. METHODS: All
participants underwent structured psychiatric diagnostic interviews immediately
after injury and at 3, 6, and 12 months. The primary outcome, QoL, was measured
using the Quality of Life Index. Covariates included demographics, injury status,
preinjury functional status, preinjury social support, and anticipation of
problems postdischarge. The General Estimating Equation was used to compare
changes in QoL between participants with and without depression over 3, 6, and 12
months, adjusting for covariates. RESULTS: An 18.1% proportion (95% confidence
interval [CI] 13.3, 22.9%) of the sample met criteria for a mood disorder in the
postinjury year. The depressed group reported a QoL that was 4.2 points (95% CI
2.8-5.6) lower in the year postinjury compared with that of the nondepressed
group. CONCLUSIONS: Depression after minor injury negatively affects QoL even a
full year postinjury. CLINICAL RELEVANCE: The findings of this study show that
patients who have injuries that are treated and discharged from an emergency
department can have significantly lower QoL in the year after that injury that is
attributed, in part, to postinjury depression. Nurses should provide anticipatory
guidance to patients that they may experience feelings of sadness or being
"blue," and that if they do, they should seek care.
PMID- 24354501
TI - Atrial tachycardia after AF ablation: an alternate mechanism?
PMID- 24354502
TI - Response to Hitman. Insulin degludec: a new insulin for today?
PMID- 24354503
TI - Construction of fast xylose-fermenting yeast based on industrial ethanol
producing diploid Saccharomyces cerevisiae by rational design and adaptive
evolution.
AB - BACKGROUND: It remains a challenge for recombinant S. cerevisiae to convert
xylose in lignocellulosic biomass hydrolysates to ethanol. Although industrial
diploid strains are more robust compared to laboratory haploid strains, however,
industrial diploid S. cerevisiae strains have been less pursued in previous
studies. This work aims to construct fast xylose-fermenting yeast using an
industrial ethanol-producing diploid S. cerevisiae strain as a host. RESULTS:
Fast xylose-fermenting yeast was constructed by genome integration of xylose
utilizing genes and adaptive evolution, including 1) Piromyces XYLA was
introduced to enable the host strain to convert xylose to xylulose; 2) endogenous
genes (XKS1, RKI1, RPE1, TKL1, and TAL1) were overexpressed to accelerate
conversion of xylulose to ethanol; 3) Candida intermedia GXF1, which encodes a
xylose transporter, was introduced at the GRE3 locus to improve xylose uptake; 4)
aerobic evolution in rich xylose media was carried out to increase growth and
xylose consumption rates. The best evolved strain CIBTS0735 consumed 80 g/l
glucose and 40 g/l xylose in rich media within 24 hours at an initial OD600 of
1.0 (0.63 g DCW/l) and produced 53 g/l ethanol. CONCLUSIONS: Based on the above
fermentation performance, we conclude that CIBTS0735 shows great potential for
ethanol production from lignocellulosic biomass.
PMID- 24354504
TI - Model study using designed selenopeptides on the importance of the catalytic
triad for the antioxidative functions of glutathione peroxidase.
AB - Although the catalytic triad of glutathione peroxidase (GPx) has been well
recognized, there was little evidence for the relevance of the interactions among
the triad amino acid residues, i.e., selenocysteine (U), glutamine (Q), and
tryptophan (W), to the GPx antioxidative functions. Using a designed
selenopeptide having an amino acid sequence of GQAUAWG, we demonstrate here that
U, Q, and W present at the active site can interact with each other to exert the
enzymatic activity. The amino acid sequence was chosen on the basis of the Monte
Carlo molecular simulation for various selenopeptides in polarizable continuous
water using the SAAP force field (SAAP-MC). Measurement of the GPx-like activity
for the selenopeptide obtained by solid-phase peptide synthesis revealed that the
antioxidant activity is cooperatively enhanced by the presence of Q and W
proximate to U, although the activity was low compared to selenocystine (U2). The
effect of Q on the activity was more important than that of W. In addition, the
fluorescence spectrometry suggested a close contact between U and W. These
experimental observations were supported by SAAP-MC simulation as well as by ab
initio calculation. The latter further suggested that the interaction mode among
the triad changes depending on the intermediate states.
PMID- 24354505
TI - Synthesis of the insecticide prothrin and its analogues from biomass-derived 5
(chloromethyl)furfural.
AB - Prothrin, a synthetic pyrethroid insecticide, was synthesized from the biomass
derived platform chemical 5-(chloromethyl)furfural in six steps and overall 65%
yield. Two structural analogues of prothrin were also prepared following the same
synthetic approach. Preliminary testing of these furan-based pyrethroids against
the yellow fever mosquito Aedes aegypti indicates promising insecticidal
activities.
PMID- 24354506
TI - Contributions of clinical disconnections and unresolved conflict to failures in
intrapartum safety.
AB - OBJECTIVE: To explore clinician perspectives on whether they experience
difficulty resolving patient-related concerns or observe problems with the
performance or behavior of colleagues involved in intrapartum care. DESIGN:
Qualitative descriptive study of physician, nursing, and midwifery professional
association members. PARTICIPANTS AND SETTING: Participants (N = 1932) were drawn
from the membership lists of the Association of Women's Health, Obstetric, and
Neonatal Nurses (AWHONN), American College of Obstetricians and Gynecologists
(ACOG), American College of Nurse Midwives (ACNM), and Society for Maternal-Fetal
Medicine (SMFM). METHODS: Email survey with multiple choice and free text
responses. Descriptive statistics and inductive thematic analysis were used to
characterize the data. RESULTS: Forty-seven percent of participants reported
experiencing situations in which patients were put at risk due to failure of team
members to listen or respond to a concern. Thirty-seven percent reported
unresolved concerns regarding another clinician's performance. The overarching
theme was clinical disconnection, which included disconnections between
clinicians about patient needs and plans of care and disconnections between
clinicians and administration about the support required to provide safe and
appropriate clinical care. Lack of responsiveness to concerns by colleagues and
administration contributed to resignation and defeatism among participants who
had experienced such situations. CONCLUSION: Despite encouraging progress in
developing cultures of safety in individual centers and systems, significant work
is needed to improve collaboration and reverse historic normalization of both
systemic disrespect and overt disruptive behaviors in intrapartum care.
PMID- 24354508
TI - Care for community-dwelling frail older people: a practice nurse perspective.
AB - AIMS AND OBJECTIVES: To evaluate care programmes for community-dwelling frail
older people from a practice nurse perspective and gain a deeper understanding of
their role within the programmes. BACKGROUND: In response to the increasing frail
population, three regions in the Netherlands implemented care programmes, in
which a proactive approach is used to identify frail older people in the
community and provide them with the appropriate care and support. DESIGN: A
constructivist grounded theory approach. METHODS: A formative process evaluation
was performed, in which study participants were practice nurses (n = 23) focusing
on the identification of and care for frail older people in primary care
settings. Based on the principles of grounded theory, data were collected via
semi-structured interviews and focus groups and analysed. RESULTS: The practice
nurses explain that 'building a trusting relationship' with the older person and
'making connections' between older people, family and other professionals are key
elements of good care in the programmes. 'Targeting the wrong audience' and
'providing good care' reflect the doubts and feelings of insecurity the practice
nurses have about the screening and selection procedures and their own role and
expertise in the programme. CONCLUSION: According to the experiences of practice
nurses, a trusting relationship with the older people is necessary to provide
good care. Practice nurses feel they should receive more support and education to
conquer issues concerning social problems in frail older people. Moreover,
practice nurses considered the screening and selection procedures to be
unsuccessful in identifying frail older people who do need care. RELEVANCE TO
CLINICAL PRACTICE: A trusting relationship should be given high priority in the
care for community-dwelling frail older people. To improve the care programmes,
screening and selection procedures need adjustments. Practice nurses should
receive more support in dealing with older people with psychosocial problems.
PMID- 24354507
TI - The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry:
design of a prospective cohort study of patients with advanced peripheral artery
disease.
AB - BACKGROUND: Advanced lower extremity peripheral artery disease (PAD), whether
presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI),
is associated with high rates of cardiovascular ischemic events, amputation, and
death. Past research has focused on strategies of revascularization, but few data
are available that prospectively evaluate the impact of key process of care
factors (spanning pre-admission, acute hospitalization, and post-discharge) that
might contribute to improving short and long-term health outcomes.
METHODS/DESIGN: The FRIENDS registry is designed to prospectively evaluate a
range of patient and health system care delivery factors that might serve as
future targets for efforts to improve limb and systemic outcomes for patients
with ALI or CLI. This hypothesis-driven registry was designed to evaluate the
contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of
leg revascularization strategies, and (iii) use of risk-reduction
pharmacotherapies, as pre-specified factors that may affect amputation-free
survival. Sequential patients would be included at an index "vascular specialist
defined" ALI or CLI episode, and patients excluded only for non-vascular
etiologies of limb threat. Data including baseline demographics, functional
status, co-morbidities, pre-hospital time segments, and use of medical therapies;
hospital-based use of revascularization strategies, time segments, and
pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial
infarction, stroke, hospitalization, and death) and limb ischemic events (e.g.,
hospitalization for revascularization or amputation) will be recorded during a
minimum of one year follow-up. DISCUSSION: The FRIENDS registry is designed to
evaluate the potential impact of key factors that may contribute to adverse
outcomes for patients with ALI or CLI. Definition of new "health system-based"
therapeutic targets could then become the focus of future interventional clinical
trials for individuals with advanced PAD.
PMID- 24354510
TI - The activation pattern of macrophages in giant cell (temporal) arteritis and
primary angiitis of the central nervous system.
AB - To determine if the pattern of macrophage activation reflects differences in the
pathogenesis and clinical presentation of giant cell arteritis and primary
angiitis of the central nervous system, specimens of 10 patients with giant cell
arteritis and five with primary angiitis of the central nervous system were
immunohistochemically studied and the expression of the macrophage activation
markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates.
Thus, a partly different expression pattern of macrophage activation markers in
giant cell arteritis and primary angiitis of the central nervous system was
observed. The group comparison revealed that giant cell arteritis cases had
significantly higher numbers of acute activated MRP14-positive macrophages,
whereas primary angiitis of the central nervous system is characterized by a
tendency toward more MRP8-positive intermediate/late activated macrophages.
Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes
were observed. These observations suggest, that despite their histopathological
similarities, giant cell arteritis and primary angiitis of the central nervous
system appear to represent either distinct entities within the spectrum of
granulomatous vasculitides or different stages of similar disease processes.
Their discrete clinical presentation is reflected by different activation
patterns of macrophages, which may characterize giant cell arteritis as a more
acute process and primary angiitis of the central nervous system as a more
advanced inflammatory process.
PMID- 24354509
TI - The relationship between sexual trauma, peritraumatic dissociation, posttraumatic
stress disorder, and HIV-related health in HIV-positive men.
AB - This study tested a novel extension of P. P. Schnurr and B. L. Green's (2004)
model of the relationships between trauma symptoms and health outcomes with
specific application to HIV-positive men. A diverse sample of 167 HIV-positive
men recruited from San Francisco Bay Area HIV clinics completed demographic,
medical, trauma history, and symptom questionnaires. Mediation analyses were
conducted using the method proposed by R. Baron and D. Kenny (1986). Regression
analyses found that sexual revictimization (SR) significantly mediated the
relationship between child sexual abuse and peritraumatic dissociation (PD), and
PD mediated the relationship between SR and current posttraumatic stress (PTS)
symptom severity. PTS symptoms partially mediated the relationship between SR and
current HIV symptom severity. The findings indicate that among HIV-positive men,
sexually revictimized men constitute a vulnerable group that is prone to PD,
which places them at risk for posttraumatic stress disorder (PTSD) and worsened
HIV-related health. Furthermore, traumatic stress symptoms were associated with
worse HIV-related symptoms, suggesting that PTS symptoms mediate the link between
trauma and health outcomes. This study highlights the need for future research to
identify the biobehavioral mediators of the PTSD-health relationship in HIV
positive individuals.
PMID- 24354511
TI - Heterogeneous interaction of H2O2 with Arizona Test Dust.
AB - The heterogeneous interaction of H2O2 with solid films of Arizona Test Dust (ATD)
was investigated under dark conditions and in presence of UV light using a low
pressure flow tube reactor coupled with a quadrupole mass spectrometer. The
uptake coefficients were measured as a function of the initial concentration of
gaseous H2O2 ([H2O2]0 = (0.18 - 5.1) * 10(12) molecules cm(-3)), irradiance
intensity (JNO2 = 0.002 - 0.012 s(-1)), relative humidity (RH = 0.002 - 69%), and
temperature (T = 268 - 320 K). The initial uptake coefficient was found to be
independent of the concentration of H2O2 and UV irradiation intensity and to
decrease with increasing RH and temperature according to the following
expressions: gamma0 = 4.8 * 10(-4)/(1+ RH(0.66)) at T = 275 K and gamma0 = 3.2 *
10(-4)/(1 + 2.5 * 10(10)exp(-7360/T)) at RH = 0.35% (calculated using BET surface
area, estimated conservative uncertainty of 30%). By contrast, the steady state
uptake coefficient was found to be independent of temperature, to increase upon
UV irradiation of the surface, and to be inversely (gammaSS ~ [H2O2](-0.6))
dependent on the concentration of H2O2. The RH independent steady state uptake
coefficient was measured under dark and UV irradiation conditions: gammaSS(dark)
= (0.95 +/- 0.30) * 10(-5) and gammaSS(UV) = (1.85 +/- 0.55) * 10(-5), for RH =
(2 - 69)% and [H2O2]0 ? 1.0 * 10(12) molecules cm(-3). The present experimental
data support current considerations that uptake of H2O2 on mineral aerosol is
potentially an important atmospheric process.
PMID- 24354512
TI - Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis
factor alpha inhibitors.
AB - PURPOSE: To evaluate the use of TNF-alpha inhibitors for non-infectious, non
necrotizing scleritis. METHODS: We conducted a retrospective chart review of
patients with non-infectious, non-necrotizing scleritis treated at our
institutions from 2002 to 2012. RESULTS: Seventeen patients (26 eyes) were
included. Ten patients were started on infliximab and seven on adalimumab; five
patients were treated with both TNF-alpha inhibitors on separate occasions. All
patients had an associated autoimmune disease. Control of active inflammation for
at least 2 months was achieved in 15 (88%) of 17 patients. Seven out of eight
patients successfully tapered concurrent corticosteroid use. Only one patient
discontinued TNF-alpha inhibitor use due to an allergic reaction. CONCLUSIONS:
TNF-alpha inhibitors appear to have a role in managing non-infectious, non
necrotizing scleritis refractory to initial therapy, mainly by reducing
inflammation and decreasing concurrent CS use.
PMID- 24354513
TI - Expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor
and prolyl hydroxylase domain protein 2 in cutaneous squamous cell carcinoma and
precursor lesions and their relationship with histological stages and clinical
features.
AB - The hypoxia-inducible factor-1 (HIF-1alpha) pathway is associated with tumor
growth, angiogenesis and metastasis in various carcinomas. Little is known
regarding the role of the HIF-1alpha signaling pathway in cutaneous squamous cell
carcinoma (SCC). We investigated the expression of HIF-1alpha, vascular
endothelial growth factor (VEGF) and the HIF negative regulator, prolyl
hydroxylase domain protein 2 (PHD2), in cutaneous SCC, Bowen's disease,
seborrheic keratosis (SK) and normal skin by immunohistochemistry and in situ
hybridization. Additionally, we explored the relationships between these factors
and the clinical and histological characteristics of each disease. Our study
indicated that the expression of HIF-1alpha and VEGF was significantly higher (P
< 0.05) in cutaneous SCC than in Bowen's disease, SK or normal skin. In contrast,
PHD2 showed significantly higher expression in normal skin compared with SK,
Bowen's disease and cutaneous SCC (P < 0.05). Grade II-IV cutaneous SCC had
higher expression levels of nuclear HIF-1alpha and cytoplasm VEGF protein but
less nuclear PHD2 protein than grade Iota cutaneous SCC (P < 0.05).
Overexpression of HIF-1alpha and VEGF, as well as the decreased expression of
PHD2, may play important roles in the development of cutaneous SCC.
PMID- 24354514
TI - A variational Bayes spatiotemporal model for electromagnetic brain mapping.
AB - In this article, we present a new variational Bayes approach for solving the
neuroelectromagnetic inverse problem arising in studies involving
electroencephalography (EEG) and magnetoencephalography (MEG). This high
dimensional spatiotemporal estimation problem involves the recovery of time
varying neural activity at a large number of locations within the brain, from
electromagnetic signals recorded at a relatively small number of external
locations on or near the scalp. Framing this problem within the context of
spatial variable selection for an underdetermined functional linear model, we
propose a spatial mixture formulation where the profile of electrical activity
within the brain is represented through location-specific spike-and-slab priors
based on a spatial logistic specification. The prior specification accommodates
spatial clustering in brain activation, while also allowing for the inclusion of
auxiliary information derived from alternative imaging modalities, such as
functional magnetic resonance imaging (fMRI). We develop a variational Bayes
approach for computing estimates of neural source activity, and incorporate a
nonparametric bootstrap for interval estimation. The proposed methodology is
compared with several alternative approaches through simulation studies, and is
applied to the analysis of a multimodal neuroimaging study examining the neural
response to face perception using EEG, MEG, and fMRI.
PMID- 24354516
TI - Left-sided grade 3 varicocele may affect the biological function of the
epididymis.
AB - OBJECTIVE: Varicocele is present in approximately 30-40% of men evaluated for
infertility and in 10-20% of the general male population, but the association
between varicocele, compromised semen quality and male infertility remains
unclear. This indicates that varicocele may impair spermatogenesis or in some
other way mitigate sperm quality. Better understanding of criteria for the
selection of men who will benefit from varicocele repair would improve the
clinical management of men with impaired semen quality and varicocele. MATERIAL
AND METHODS: To further understand the effect of varicocele repair by
embolization in men with grade 3 varicocele, 50 men referred for infertility with
varicocele were evaluated before and after embolization. RESULTS: There was a
significant improvement in total sperm count (25.5 +/- 4.7 million to 78 +/- 11
million, p < 0.001) and sperm motility (slowly and rapidly progressive) (31.5 +/-
2.9% to 45 +/- 2.5%, p < 0.001) after spermatic vein embolization, comparing
baseline to 3 month post-treatment follow-up data. Furthermore, alpha-glucosidase
(specific epididymis-derived protein) increased from 61.7 +/- 5.7 U to 84.7 +/-
7.0 U (p < 0.05) and sperm droplets decreased from 14.2 +/- 1.5% to 11.0 +/- 1.0%
(p < 0.05). CONCLUSION: The results indicate improved epididymal function and
suggest that left-sided grade 3 varicocele may affect the epididymis in addition
to effects on the testis.
PMID- 24354515
TI - Ultrasound elastography of the liver, spleen, and kidneys in clinically normal
cats.
AB - A large amount of overlap exists in the B-mode ultrasound appearance of normal
and abnormal liver, spleen, and kidney tissues in cats. Therefore, invasive
tissue sampling procedures remain the standard method for diagnosing diseases in
these organs. The purpose of our study was to assess the feasibility of
ultrasound elastography as a technique for improving noninvasive characterization
of the feline liver, spleen, and kidneys. Elastography was performed on 10
unsedated, clinically healthy cats. Numeric (strain) values (0 = softest to 255 =
firmest) assigned to color pixels within regions of interest resulted in median
scores (interquartile ranges) of body wall, 207.50 (189.75-224.00); liver, 119.00
(105.00-138.25); spleen, 127.50 (121-00-142.00); right renal cortex, 83.50 (64.00
130.00); right renal near field, 125.50 (110.75-139.75); left renal cortex, 77.50
(52.00-116.25); and left renal near field, 126.00 (114.00-145.25). Strain values
were not different between organs. Body wall median was the only significantly
different value (P < 0.05). Strain ratio values of body wall:organ were as
follows: liver, 1.76 (1.38-2.00); spleen, 1.68 (1.47-1.83); right renal cortex,
2.31 (1.61-3.15); right renal near field, 1.62 (1.41-2.01); left renal cortex,
2.66 (1.45-4.13); and left renal near field, 1.51 (1.29-1.89). Subjectively,
hepatic and splenic parenchymal tissues were homogeneous in compressibility and
similar in elasticity to one another. Renal cortical tissue was softer compared
to medullary tissue. Findings indicated that ultrasound elastography is a
feasible technique for objectively and subjectively characterizing the feline
liver, spleen, and kidneys. Further research is needed in cats with confirmed
diseases of these organs, to compare the diagnostic sensitivity of ultrasound
elastography vs. B-mode ultrasonography.
PMID- 24354517
TI - Nitrogen dioxide regulates organ growth by controlling cell proliferation and
enlargement in Arabidopsis.
AB - * To gain more insight into the physiological function of nitrogen dioxide (NO2),
we investigated the effects of exogenous NO2 on growth in Arabidopsis thaliana. *
Plants were grown in air without NO2 for 1 wk after sowing and then grown for 1-4
wk in air with (designated treated plants) or without (control plants) NO2.
Plants were irrigated semiweekly with a nutrient solution containing 19.7 mM
nitrate and 10.3 mM ammonium. * Five-week-old plants treated with 50 ppb NO2
showed a <= 2.8-fold increase in biomass relative to controls. Treated plants
also showed early flowering. The magnitude of the effects of NO2 on leaf
expansion, cell proliferation and enlargement was greater in developing than in
maturing leaves. Leaf areas were 1.3-8.4 times larger on treated plants than
corresponding leaves on control plants. The NO2-induced increase in leaf size was
largely attributable to cell proliferation in developing leaves, but was
attributable to both cell proliferation and enlargement in maturing leaves. The
expression of different sets of genes for cell proliferation and/or enlargement
was induced by NO2, but depended on the leaf developmental stage. * Collectively,
these results indicated that NO2 regulates organ growth by controlling cell
proliferation and enlargement.
PMID- 24354518
TI - Functional impacts of exoskeleton-based rehabilitation in chronic stroke: multi
joint versus single-joint robotic training.
AB - Stroke is a major cause of disability in the world. The activities of upper limb
segments are often compromised following a stroke, impairing most daily tasks.
Robotic training is now considered amongst the rehabilitation methods applied to
promote functional recovery. However, the implementation of robotic devices
remains a major challenge for the bioengineering and clinical community. Latest
exoskeletons with multiple degrees of freedom (DOF) may become particularly
attractive, because of their low apparent inertia, the multiple actuators
generating large torques, and the fact that patients can move the arm in the
normal wide workspace. A recent study published in JNER by Milot and colleagues
underlines that training with a 6-DOF exoskeleton impacts positively on motor
function in patients being in stable phase of recovery after a stroke. Also,
multi-joint robotic training was not found to be superior to single-joint robotic
training. Although it is often considered that rehabilitation should start from
simple movements to complex functional movements as the recovery evolves, this
study challenges this widespread notion whose scientific basis has remained
uncertain.
PMID- 24354519
TI - Tissue kallikrein preventing the restenosis after stenting of symptomatic MCA
atherosclerotic stenosis (KPRASS).
AB - RATIONALE: Many recent studies suggest that the kallikrein-kinin system play a
protective role in the impairment of vascular smooth muscle cells and vascular
endothelial cell. AIMS: The study aims to determine whether tissue kallikrein is
efficacy for preventing the long-term in-stent restenosis after stenting of
symptomatic atherosclerotic stenosis of the middle cerebral artery M1 segment.
DESIGN: This is a Phase II, randomized, single-blinded, controlled trial. In line
with SAMMPRIS stenting indications, patients (n = 90) with the symptomatic the
middle cerebral artery M1 segment stenosis >= 70% and successfully treated with
stent will be enrolled. Eligible patients will be randomized using computer
generated numbers, and allocated to receive tissue kallikrein treatment or not.
Patients in tissue kallikrein treatment group will be prescribed with intravenous
infusion of tissue kallikrein (0.15 PNAU/d, dissolved in 100 ml saline) for 7
days after stenting and then oral administration of pancreatic kallikrein enteric
coated tablet (240 U, 3/d) to the end of study. As the foundation treatment, all
the enrolled patients will receive aspirin (100 mg/d), clopidogrel (75 mg/d), and
atorvastatin (20 mg/d) for the first 6 months and continue with the combination
of aspirin and atorvastatin at the previous dosage. STUDY OUTCOMES: Patients will
be evaluated at 1, 6 and 12 months after stenting. The primary outcomes are the
in-stent restenosis rate, new stroke or aggravation of the previous ischemic
stroke ipsilateral to the severe stenotic artery. Secondary outcomes include
stroke of other artery territories, myocardial infarction and vascular death.
Modification of stroke knowledge, exercise and diet habit, smoking cessation and
available laboratory data will also be recorded. CONCLUSION: As our pilot study,
tissue kallikrein would be expected to prevent the long-term in-stent restenosis
after stenting of the symptomatic middle cerebral artery dramatically.
PMID- 24354521
TI - Emerging drugs for acute lymphocytic leukemia.
AB - INTRODUCTION: Acute lymphoblastic leukemia (ALL) is typically treated with
complex multi-agent chemotherapy regimens over a prolonged time period. Long-term
outcomes depend on the age of the patient and the biological characteristics of
the leukemic cells. While pediatric patients achieve cure more often than adults,
therapy can continue to be improved for all patients with this disease. AREAS
COVERED: The current management strategy for ALL is reviewed. Recently, targeted
therapies have been shown to improve survival in subsets of patients, most
notably in those with Philadelphia chromosome-positive ALL or with leukemic cells
that express the surface antigen CD20. Several innovative compounds are under
investigation, and the most promising ones to date will be discussed. EXPERT
OPINION: The incorporation of monoclonal antibody therapy represents a targeted
and powerful approach to the management of ALL. Bispecific T-cell engaging
agents, such as blinatumomab, are able to facilitate immune-mediated killing of
leukemia cells. Immunoconjugates (i.e., monoclonal antibodies linked to various
cytotoxins) allow small doses of very potent chemotherapy to be delivered
directly to a leukemia cell with hope of sparing normal tissue. As the genetic
and molecular characterization of ALL is more completely understood, patients
will receive treatment plans that are more individualized than previously
possible.
PMID- 24354520
TI - Comparing the anterior nare bacterial community of two discrete human populations
using Illumina amplicon sequencing.
AB - The anterior nares are an important reservoir for opportunistic pathogens and
commensal microorganisms. A barcoded Illumina paired-end sequencing method
targeting the 16S ribosomal RNA V1-2 hypervariable region was developed to
compare the bacterial diversity of the anterior nares across distinct human
populations (volunteers from Germany vs a Babongo Pygmy tribe, Africa). Of the
251 phylotypes detected, 231 could be classified to the genus level and 109 to
the species level, including the unambiguous identification of the ubiquitous
Staphylococcus aureus and Moraxella catarrhalis. The global bacterial community
of both adult populations revealed that they shared 85% of the phylotypes,
suggesting that our global bacterial communities have likely been with us for
thousands of years. Of the 34 phylotypes unique to the non-westernized
population, most were related to members within the suborder Micrococcineae.
There was an even more overwelming distinction between children and adults of the
same population, suggesting a progression of a childhood community of high
diversity comprising species of Moraxellaceae and Streptococcaceae to an adult
community of lower diversity comprising species of Propionibacteriaceae,
Clostridiales Incertae Sedis XI, Corynebacteriaceae and Staphylococcaceae. Thus,
age was a stronger factor for accounting for differing bacterial assemblages than
the origin of the human population sampled.
PMID- 24354522
TI - A history of unemployment or sick leave influences long-term functioning and
health-related quality-of-life after severe traumatic brain injury.
AB - PRIMARY OBJECTIVE: The consequences of pre-morbid factors in adults with severe
traumatic brain injury have not been widely addressed. This study aimed to
determine whether being unemployed or on sick leave before injury influences long
term health-related quality-of-life (HRQoL) and functioning in patients with
severe traumatic brain injury. SUBJECTS: Fifty-one consecutive patients were
studied; aged 16-65 years, with severe traumatic brain injury who were admitted
to Sahlgrenska University Hospital, Gothenburg, from 1999-2002. METHODS: The
patients were assessed once, 2-11 years after trauma. Data from the time of
injury were combined into a validated prognostic model to adjust for injury
severity. Data on sick leave and unemployment before injury were gathered from
the Swedish social insurance agency. Outcomes were measured with the Short Form
36 Health Survey, the Glasgow Outcome Scale-Extended, and a self-report
questionnaire specifically designed for this study to measure functioning.
RESULTS: In a multivariate analysis, a history of sick leave/unemployment
predicted a worse long-term global outcome, more problems with personal
activities of daily living and worse HRQoL. CONCLUSION: These results should be
considered when refining outcome predictions and optimizing rehabilitation
interventions for patients with severe traumatic brain injury.
PMID- 24354523
TI - Ammonia-rich high-temperature superconducting intercalates of iron selenide
revealed through time-resolved in situ X-ray and neutron diffraction.
AB - The development of a technique for following in situ the reactions of solids with
alkali metal/ammonia solutions, using time-resolved X-ray diffraction methods,
reveals high-temperature superconducting ammonia-rich intercalates of iron
selenide which reversibly absorb and desorb ammonia around ambient temperatures.
PMID- 24354524
TI - Rare variants in methionyl- and tyrosyl-tRNA synthetase genes in late-onset
autosomal dominant Charcot-Marie-Tooth neuropathy.
PMID- 24354525
TI - MicroRNAs: are they the missing link between hypoxia and pre-eclampsia?
AB - Pre-eclampsia is a multisystem disorder that occurs in the second half of
pregnancy affecting 5% of pregnancies. It remains the leading cause of maternal
and perinatal mortality and morbidity worldwide. Impaired placental implantation,
hypoxia, endothelial dysfunction and systemic inflammation are thought to have a
role in the pathogenesis of pre-eclampsia. MicroRNAs (miRNAs) are short non
coding RNAs. They are important regulators of gene expression and have been found
to affect cell development, proliferation, differentiation and function. Specific
patterns of miRNAs have been detected in the placenta and there is altered miRNA
expression in the placenta of patients with pre-eclampsia to but their role in
the pathogenesis remains unclear. Furthermore, deregulated miRNAs have also been
reported in human villous trophoblasts during hypoxic stress. One of the more
consistently elevated miRNAs by hypoxia and in the placenta of patients with pre
eclampsia is miR-210. Whether such miRNAs are bystander markers of hypoxia, or
are directly involved in the pathogenesis of pre-eclampsia, needs to be
clarified. There is potential for miRNAs to be used as predictors, markers or
therapy in pre-eclampsia. This review provides current knowledge about miRNAs,
particularly hypoxia-related miRNAs and the interaction of hypoxia, miRNAs and
placenta in pre-eclampsia.
PMID- 24354526
TI - From nature to market: examples of natural products that became drugs.
AB - Nature is an irrefutable source of inspiration for the modern man in many
aspects. The observation and understanding of nature have allowed the development
of new materials, new sources of energies, new drugs etc. Specifically, natural
products provide a great contribution to the development of new agents for the
treatment of infections and antitumor agents. However, obtaining natural products
directly from animals, fungi, bacteria, plants etc has been considered not enough
to attend the high demand by pharmaceutical industries. In this regard, various
strategies based on biotechnological processes or synthetic approaches have been
developed. In this scenario the total synthesis can be undoubtedly a useful and
powerful tool for obtaining higher amounts of natural products and/or structural
modifications thereof. Herein, we emphasize successful examples of total
synthesis of galanthamine, morphine, paclitaxel and podophyllotoxin - natural
products approved as pharmaceuticals.
PMID- 24354527
TI - Comparative mass spectrometry & nuclear magnetic resonance metabolomic approaches
for nutraceuticals quality control analysis: a brief review.
AB - The number of botanical dietary supplements in the market has recently increased
primarily due to increased health awareness. Standardization and quality control
of the constituents of these plant extracts is an important topic, particularly
when such ingredients are used long term as dietary supplements, or in cases
where higher doses are marketed as drugs. The development of fast, comprehensive,
and effective untargeted analytical methods for plant extracts is of high
interest. Nuclear magnetic resonance spectroscopy and mass spectrometry are the
most informative tools, each of which enables high-throughput and global analysis
of hundreds of metabolites in a single step. Although only one of the two
techniques is utilized in the majority of plant metabolomics applications, there
is a growing interest in combining the data from both platforms to effectively
unravel the complexity of plant samples. The application of combined MS and NMR
in the quality control of nutraceuticals forms the major part of this review.
Finally I will look at the future developments and perspectives of these two
technologies for the quality control of herbal materials.
PMID- 24354528
TI - Introduction to metabolic genetic engineering for the production of valuable
secondary metabolites in in vivo and in vitro plant systems.
AB - Plants are capable of producing a myriad of chemical compounds. While these
compounds serve specific functions in the plant, many have surprising effects on
the human body, often with positive action against diseases. These compounds are
often difficult to synthesize ex vivo and require the coordinated and
compartmentalized action of enzymes in living organisms. However, the amounts
produced in whole plants are often small and restricted to single tissues of the
plant or even cellular organelles, making their extraction an expensive process.
Since most natural products used in therapeutics are specialized, secondary plant
metabolites, we provide here an overview of the classification of the main
classes of these compounds, with its biochemical pathways and how this
information can be used to create efficient in and ex planta production pipelines
to generate highly valuable compounds. Metabolic genetic engineering is
introduced in light of physiological and genetic methods to enhance production of
high-value plant secondary metabolites.
PMID- 24354529
TI - Disorders of primary metabolites in response to drought may increase the
synthesis of natural products for medicinal purposes: South American herbs - a
case study.
AB - The use of plants for healing diseases is one of the oldest medical practices and
there are several studies showing that botany and medicine are related. Recent
researches have shown that around 25% of new chemical entities and 42% of
anticancer drugs marketed worldwide from 1981 to 2006 are obtained from natural
products and their derivatives. One-third of the botanical biodiversity of the
planet is in South American tropical ecosystems (Neotropical). Over the
centuries, plants have been used by indigenous people for curing diseases. This
strong tradition has been a great challenge for the scientific community in order
to validate the folkloric medicinal use of herbs. In this way, a very few
Neotropical pharmaceutical products have reached the market in industrialized
countries, even though they have a considerable plant diversity. Plants
synthesize several organic compounds which are not related to their growth and
development and are called secondary metabolites or natural products that are
derived from central or primary metabolism. Because plants are sessile organisms,
they have to respond quickly to environmental changes in order to escape and
survive under unfavorable conditions. Drought is one of the most worldwide
serious impediments for crop yields producing adverse negative effects on plant
growth, by impacting leaves and roots growth, stomatal conductance,
photosynthetic rate and biomass gain. The three major classes of secondary
metabolites are produced from pathways of different primary metabolites,
including glycolysis, tricarboxilic acid cycle, aliphatic amino acids, pentose
phosphate pathway, shikimate pathway and aromatic amino acids. This review
compiles the metabolic changes occurring at primary metabolite level and total
biosynthesis of natural products with potential for the development of new drugs
in response to drought.
PMID- 24354530
TI - Withanolides from Withania somnifera Dunal: development of cellular technology
and their production.
AB - Withania somnifera Dunal is one of the most commonly used plants in Ayurvedic and
indigenous system of medicine in India for over thousands of years. In view of
its varied therapeutic potential, the plant has also been the subject of
considerable scientific attention. The major chemical constituents of the
Withania genus, the withanolides, are a group of naturally occurring C28
steroidal lactones built on an intact or rearranged ergostane framework, in which
C22 and C26 are oxidized to form a six-member lactone ring. In recent years,
numerous pharmacological investigations have been carried out utilizing W.
somnifera extracts and several patents have been filed on pharmacological and
medicinal importance of withanolides and extracts of W. somnifera, individually
or in combination. Considering the immense importance of withanolides for
medicinal purposes, the establishment of strategies to improve withanolides yield
are highly desirable. Under natural conditions, W. somnifera possesses restricted
levels of withanolides then, alternatives for obtaining withanolides in better
yields are imperative. In vitro approaches followed by metabolic engineering
could be attractive tools to achieve this goal. Therefore, we present here an
overview of the development of various protocols for in vitro tissue regeneration
from W. somnifera and in vitro secondary metabolite production as well. The
review also gives an account of selected patents on various important activities
of phytochemicals and extracts of W. somnifera.
PMID- 24354531
TI - Stressing conditions as tools to boost the biosynthesis of valuable plant natural
products.
AB - There is a consensus that plants are great sources of metabolites with a broad
variety of functions. This is particularly important because plants cannot run
away from environmental conditions that can threat their existence. The numerous
biological activities exhibited by plant natural products prompted humanity to
use such substances or their derivatives for the treatment and/or prevention of
diseases. The more we know the flora around the world the higher is the chance to
find new lead compounds for the design of more potent drugs or nutraceuticals.
This review first deals with Brazilian flora, contextualizing the most studied
medicinal species and related patents. It also describes a compilation of
relevant works based on the use of stress conditions to enhance the biosynthesis
of valuable metabolites in cell cultures, tissue cultures (hairy roots) and whole
plants by using native or crop plants around the world.
PMID- 24354532
TI - Naturally occurring calanolides: an update on their anti-HIV potential and total
syntheses.
AB - Calanolides are naturally occurring pyranocoumarins found particularly in
Calophyllum species (family Clusiaceae/ Guttiferae), and are well known for their
potent anti-human immunodeficiency virus (HIV) activity. Various preclinical and
clinical studies with this class of compounds are going on, and the National
Cancer Institute (NCI) has been playing an active and supportive role in this
regard. The present review covers an up-to-date literature of naturally occurring
calanolides in view of their anti-HIV potential and total syntheses including
information on related patents.
PMID- 24354535
TI - Joint health scores in a haemophilia A cohort from Pakistan with minimal or no
access to factor VIII concentrate: correlation with thrombin generation and
underlying mutation.
AB - Haemophilia A is associated with recurrent joint bleeding which leads to
synovitis and debilitating arthropathy. Coagulation factor VIII level is an
important determinant of bleed number and development of arthropathy . The aim of
this study was to compare the haemophilia joint health score (HJHS) and Gilbert
score with severity, age, thrombin generation (TG) and underlying mutation in a
haemophilia A cohort which had minimal access to haemostatic replacement therapy.
Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at
first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert
score were recorded. A strong correlation was found between HJHS and Gilbert
score (r = 0.98), both were significantly higher in severe (n = 59) compared with
non-severe (n = 29) individuals before the age of 12 years (P <= 0.01) but not
thereafter. When individuals were divided according to developmental age (<12
years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly
lower in the youngest group (P <= 0.001), there was no difference between 12-16
years and >16 years. In severe individuals there was no correlation between in
vitro TG and joint score, whereas in non-severe individuals there was a weak
negative correlation. In the severe group, no significant difference was observed
for either joint score according to the underlying mutation type (inversion,
missense, nonsense, frameshift). In this cohort of haemophilia A individuals with
minimal access to haemostatic treatment, haemophilic arthropathy correlated with
severity and age; among severe individuals, joint health scores did not relate to
either the underlying mutation or in vitro TG.
PMID- 24354533
TI - Biosynthesis and metabolic engineering of anthocyanins in Arabidopsis thaliana.
AB - Arabidopsis thaliana is the first model plant, the genome of which has been
sequenced. In general, intensive studies on this model plant over the past nearly
30 years have led to many new revolutionary understandings in every single aspect
of plant biology. Here, we review the current understanding of anthocyanin
biosynthesis in this model plant. Although the investigation of anthocyanin
structures in this model plant was not performed until 2002, numerous studies
over the past three decades have been conducted to understand the biosynthesis of
anthocyanins. To date, it appears that all pathway genes of anthocyanins have
been molecularly, genetically and biochemically characterized in this plant.
These fundamental accomplishments have made Arabidopsis an ideal model to
understand the regulatory mechanisms of anthocyanin pathway. Several studies have
revealed that the biosynthesis of anthocyanins is controlled by WD40-bHLH-MYB
(WBM) transcription factor complexes under lighting conditions. However, how
different regulatory complexes coordinately and specifically regulate the pathway
genes of anthocyanins remains unclear. In this review, we discuss current
progresses and findings including structural diversity, regulatory properties and
metabolic engineering of anthocyanins in Arabidopsis thaliana.
PMID- 24354536
TI - Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat
forebrain stem cells.
AB - Specific GABAergic interneurons in the hilus are lost in animal models with
temporal-lobe epilepsy (TLE). Some preclinical evidence has indicated that
GABAergic cells may provide relief from seizures in these models. This study was
aimed to examine the ability of ethosuximide, an anticonvulsant drug, to promote
neurogenesis in 3-day-old rat forebrain cortex stem cells. Most of the cells were
found to be nestin-positive undifferentiated neural stem cells prior to their
exposure to ethosuximide. It was noted that the number and percentage of tubulin
beta-III immunopositive neurons were increased after 6 days treatment with
ethosuximide. Upon bFGF withdrawal, exposure to ethosuximide differentiated the
stem cells to MAP2 positive neural cells (7.18 +/- 0.43, 21.766 +/- 0.55 and
41.57 +/- 0.5 for control, 0.1 and 1 MUM, respectively). GABA immunofluorescence
images illustrated that ethosuximide increased GABAergic neurons (7.19 +/- 0.32,
23.23 +/- 0.55, and 46.30 +/- 0.44 for control, 0.1 and 1 MUM, respectively).
Additionally, BrdU immunofluorescence assay showed that ethosuximide-enhanced
nucleus proliferation in the neuronal stem cells. Therefore, the results of this
study suggest that ethosuximide may compensate damage caused by seizure attacks
and possibly other neuronal loss disorders.
PMID- 24354534
TI - Number of teeth, C-reactive protein, fibrinogen and cardiovascular mortality: a
15-year follow-up study in a Finnish cohort.
AB - AIM: To test whether the number of teeth, an inverse proxy for composite oral
infection scores is associated with better survival. MATERIALS AND METHODS: The
Kuopio Oral Health and Heart study initiated a case-control study in 1995-1996
consisting of 256 consecutive coronary artery disease patients and 250 age and
gender-matched controls. We appended the mortality data and formulated a
longitudinal study. By May 31st, 2011, 124 mortalities had occurred and 80 of
which were of cardiovascular origin. Using Cox proportional hazards models, we
assessed the association of the teeth group (Teethgrp) - consisting of 10 teeth -
with cardiovascular and all-cause mortality after 15.8 years of median follow-up.
RESULTS: In multivariate models, with the edentulous state as reference, one
level increase in Teethgrp was associated with significantly increased survival
from cardiovascular disease (CVD) mortality with a Hazard Ratio (HR) 0.73, p
value = 0.02 but not with all-cause mortality (HR = 0.87, p = 0.13). The findings
were not mediated by C-reactive protein (CRP) levels >=3 mg/L or by median
fibrinogen levels, but were mediated by CRP levels >5 mg/L. CONCLUSION: Each
increment of 10 teeth from the edentulous state was associated with a 27%
improved CVD survival, independent of low-grade systemic inflammation.
PMID- 24354537
TI - Managed ventricular pacing facilitating atrioventricular nodal reentrant
tachycardia.
PMID- 24354538
TI - Glucose-induced inhibition of insulin secretion.
AB - Increase in glucose is known to elevate the concentration of cytoplasmic Ca(2+)
([Ca(2+) ]i ) in pancreatic beta-cells and stimulate insulin secretion. However,
rise of glucose can also lower [Ca(2+) ]i and inhibit insulin release. In the
present review, we examine the mechanisms for this inhibition and highlight its
importance for the healthy beta-cell and the development of diabetes. It is
possible to distinguish between 60 and 90 s of prompt inhibition and the late
inhibition seen after the first-phase peak of insulin release. The introductory
inhibition is characteristic of the healthy beta-cell and mediated by
sequestration of [Ca(2+) ]i in the endoplasmic reticulum. This inhibition is
easily seen in studies of isolated islets but too brief to be detected in a
conventional intravenous glucose tolerance test. Coupled to simultaneous rise of
glucagon, the introductory suppression of insulin release is the starting point
for the antiphase relation between the subsequent insulin and glucagon pulses.
Another effect of the initial suppression is to increase the pool of readily
releasable granules responsible for the first-phase release of insulin. The
presence of late inhibition of insulin release is an indicator of beta-cell
dysfunction. Patients with type 2 diabetes often respond to intravenous bolus
injection of glucose with 5-10 min of late suppression of circulating insulin.
PMID- 24354539
TI - Hypoproteinemia in the second trimester among patients with preeclampsia prior to
the onset of clinical symptoms.
AB - OBJECTIVE: To find a risk factor for "uncomplicated" preeclampsia (PE) comparing
blood biochemical parameters between women with uncomplicated PE and healthy
pregnant women in each trimester of pregnancy. METHODS: A retrospective study was
performed on 83 cases of uncomplicated PE, selected from 434 patients with PE,
disregarding subjects with other complications relevant to hypertension during
pregnancy. The study was limited to women with PE occurring in the third
trimester, and records of blood biochemical parameters were evaluated. Controls
were recruited from 108 healthy volunteers with normal singleton pregnancies.
RESULTS: A significant decrease in total protein was observed in the
uncomplicated PE group in the second trimester prior to the onset of clinical
symptoms. CONCLUSION: Hypoproteinemia during pregnancy may be a risk factor for
this pathophysiology, and the maintenance of sufficient protein in early
pregnancy could contribute to prophylaxis for women with uncomplicated PE.
PMID- 24354540
TI - Hot-electron-induced dissociation of H2 on gold nanoparticles supported on SiO2.
AB - Hot-electron-induced photodissociation of H2 was demonstrated on small Au
nanoparticles (AuNPs) supported on SiO2. The rate of dissociation of H2 was found
to be almost 2 orders of magnitude higher than that observed on equivalently
prepared AuNPs on TiO2. The rate of H2 dissociation was found to be linearly
dependent on illumination intensity with a wavelength dependence resembling the
absorption spectrum of the plasmon of the AuNPs. This result provides strong
additional support for the hot-electron-induced mechanism for H2 dissociation in
this photocatalytic system.
PMID- 24354541
TI - Comparing open and closed techniques of frontalis suspension with silicone rod
for the treatment congenital blepharoptosis.
AB - PURPOSE: To compare open and closed methods of the frontalis suspension operation
with a silicone rod in the treatment of congenital blepharoptosis. METHODS: Forty
four cases with unilateral or bilateral congenital ptosis with a poor levator
function of < 4 mm were divided randomly into two groups. Each group underwent an
eyelid crease incision operation (open) or a supralash stab incision (closed).
Ptosis was measured by the difference between the upper eyelid margin reflex
distance (MRD) of the affected eyelids of the unilateral and bilateral cases.
Frequent follow-up examinations were performed up to 12 months post-surgery.
RESULTS: Associated ophthalmologic findings showed that amblyopia, strabismus,
wound discharge and knot dehiscence problems were present in 36.6%, 27.3%, 8.5%
and 8.5% of the patients, respectively. There was no significant difference
between the abovementioned associated ophthalmic findings of the two operative
methods studied (P = 0.37). The difference in the surgical methods and MRD 3, 6
and 12 months after operation did not reach statistical significance. Similar
results for good MRD (3 < MRD < 5) were found in closed (54.5%, 12/22) and open
(54.5%, 12/22) methods, while 40.9% (9/22) and 45.5% (10/22) of cases were
attributed to the under correction group in the closed and open methods,
respectively. In bilaterally operated cases, MRD was more symmetrical than in
unilaterally operated eyes. The symmetry of MRD and the eyelid crease was more
prevalent in the open technique group. CONCLUSIONS: The frontalis sling operation
using a silicone rod exhibited better results, in terms of symmetry, in the open
technique in comparison to the closed method.
PMID- 24354542
TI - Hand contour detection in wearable camera video using an adaptive histogram
region of interest.
AB - BACKGROUND: Monitoring hand function at home is needed to better evaluate the
effectiveness of rehabilitation interventions. Our objective is to develop
wearable computer vision systems for hand function monitoring. The specific aim
of this study is to develop an algorithm that can identify hand contours in video
from a wearable camera that records the user's point of view, without the need
for markers. METHODS: The two-step image processing approach for each frame
consists of: (1) Detecting a hand in the image, and choosing one seed point that
lies within the hand. This step is based on a priori models of skin colour. (2)
Identifying the contour of the region containing the seed point. This is
accomplished by adaptively determining, for each frame, the region within a
colour histogram that corresponds to hand colours, and backprojecting the image
using the reduced histogram. RESULTS: In four test videos relevant to activities
of daily living, the hand detector classification accuracy was 88.3%. The contour
detection results were compared to manually traced contours in 97 test frames,
and the median F-score was 0.86. CONCLUSION: This algorithm will form the basis
for a wearable computer-vision system that can monitor and log the interactions
of the hand with its environment.
PMID- 24354543
TI - Evaluation of a diabetes nurse specialist prescribing project.
AB - AIMS AND OBJECTIVES: To evaluate the diabetes nurse specialist prescribing
project with the aim of determining whether diabetes nurse specialist prescribing
is safe and effective and to inform the implementation and extension of
registered nurse prescribing. BACKGROUND: Registered nurses in many countries are
able to prescribe medicines, but in New Zealand, prior to the diabetes nurse
specialist project, nurse practitioners were the only nurses who could prescribe
medicines. New regulations allowed the nurses to prescribe a limited number of
prescription medicines. DESIGN: The study was a process and outcome clinical
programme evaluation. METHODS: The project took place between April-September
2011 and involved 12 diabetes nurse specialist in four localities. Quantitative
data were collected from clinical records maintained by the diabetes nurse
specialist for the project (1274 patients and 3402 prescribing events), from
surveys with stakeholders (general practitioners, n = 30; team members, n = 19;
and patients, n = 89) and audits from patient notes (n = 117) and prescriptions
(n = 227), and qualitative data from interviews with project participants (n =
18) and patients (n = 19). All data were analysed descriptively. RESULTS:
Diabetes nurse specialist prescribing was determined to be safe, of high quality
and appropriate. It brought important benefits to the effectiveness of specialist
diabetes services, was acceptable to patients and was supported by the wider
healthcare team. CONCLUSIONS: These findings are consistent with the findings
reported in the international literature about nurse prescribing in a range of
different practice areas. Clarification of the education and competence
requirements and resourcing for the ongoing supervision of nurses is recommended
if the prescribing model is to be extended. RELEVANCE TO CLINICAL PRACTICE:
Diabetes nurse specialist prescribing improved access to medicines by providing a
more timely service. Nurses felt more satisfied with their work because they
could independently provide a complete episode of care. As novice prescribers,
nurses need to be well prepared educationally and have access to supportive
clinical supervision.
PMID- 24354544
TI - Identification of a novel, nanobody-induced, mechanism of TAFI inactivation and
its in vivo application.
AB - BACKGROUND: Down-regulation of fibrinolysis due to cleavage of C-terminal lysine
residues from partially degraded fibrin is mainly exerted by the carboxypeptidase
activity of activated thrombin-activatable fibrinolysis inhibitor (TAFIa).
Recently, some intrinsic carboxypeptidase activity (i.e. zymogen activity) was
reported for the proenzyme (TAFI); however, there is some discussion about its
ability to cleave high molecular weight substrates. OBJECTIVE: We aimed to
identify and characterize nanobodies toward mouse TAFI (mTAFI) that stimulate the
zymogen activity and to test their effect in an in vitro clot lysis assay and an
in vivo mouse thromboembolism model. METHODS AND RESULTS: Screening of a library
of nanobodies toward mTAFI revealed one nanobody (VHH-mTAFI-i49) that
significantly stimulates the zymogen activity of mTAFI from undetectable (< 0.35
U mg-1) to 4.4 U mg-1 (at a 16-fold molar ratio over mTAFI). The generated
carboxypeptidase activity is unstable at 37 degrees C. Incubation of mTAFI with
VHH-mTAFI-i49 revealed a time-dependent reduced activatability of mTAFI. Epitope
mapping revealed that Arg227 and Lys212 are important for the nanobody/mTAFI
interaction and suggest destabilization of mTAFI by disrupting the stabilizing
interaction between the activation peptide and the dynamic flap region. In vitro
clot lysis experiments revealed an enhanced clot lysis due to a reduced
activation of mTAFI during clot formation. In vivo application of VHH-mTAFI-i49
in a mouse thromboembolism model decreased dose-dependently the fibrin deposition
in the lungs of thromboembolism-induced mice. CONCLUSION: The novel, nanobody
induced, reduced activatability of mTAFI demonstrates to be a very potent
approach to enhance clot lysis.
PMID- 24354545
TI - A coumarin-specific prenyltransferase catalyzes the crucial biosynthetic reaction
for furanocoumarin formation in parsley.
AB - Furanocoumarins constitute a sub-family of coumarin compounds with important
defense properties against pathogens and insects, as well as allelopathic
functions in plants. Furanocoumarins are divided into two sub-groups according to
the alignment of the furan ring with the lactone structure: linear psoralen and
angular angelicin derivatives. Determination of furanocoumarin type is based on
the prenylation position of the common precursor of all furanocoumarins,
umbelliferone, at C6 or C8, which gives rise to the psoralen or angelicin
derivatives, respectively. Here, we identified a membrane-bound prenyltransferase
PcPT from parsley (Petroselinum crispum), and characterized the properties of the
gene product. PcPT expression in various parsley tissues is increased by UV
irradiation, with a concomitant increase in furanocoumarin production. This
enzyme has strict substrate specificity towards umbelliferone and dimethylallyl
diphosphate, and a strong preference for the C6 position of the prenylated
product (demethylsuberosin), leading to linear furanocoumarins. The C8-prenylated
derivative (osthenol) is also formed, but to a much lesser extent. The PcPT
protein is targeted to the plastids in planta. Introduction of this PcPT into the
coumarin-producing plant Ruta graveolens showed increased consumption of
endogenous umbelliferone. Expression of PcPT and a 4-coumaroyl CoA 2'-hydroxylase
gene in Nicotiana benthamiana, which does not produce furanocoumarins, resulted
in formation of demethylsuberosin, indicating that furanocoumarin production may
be reconstructed by a metabolic engineering approach. The results demonstrate
that a single prenyltransferase, such as PcPT, opens the pathway to linear
furanocoumarins in parsley, but may also catalyze the synthesis of osthenol, the
first intermediate committed to the angular furanocoumarin pathway, in other
plants.
PMID- 24354546
TI - Does the new formulation of OxyContin(r) deter misuse? A qualitative analysis.
AB - The purpose of this qualitative study is to understand changing illicit drug use
patterns in rural Appalachia since a new formulation of OxyContin(r) was released
with the goal of deterring diversion and misuse. Participants (n = 25) from a
longitudinal study of rural drug users (N = 192) were approached to participate
in semistructured qualitative interviews between April and June 2011. The primary
finding is that the majority of participants switched from using the original
formulation OxyContin to immediate-release oxycodone. We discuss the implications
and limitations of these findings.
PMID- 24354547
TI - Barriers to drug use behavior change among primary care patients in urban United
States community health centers.
AB - In 2011 and 2012, 147 patients in urban United States Community Health Centers
who misused drugs, but did not meet criteria for drug dependence, received a
brief intervention as part of a National Institute on Drug Abuse-funded clinical
trial of a screening and brief intervention protocol. Potential study
participants were identified using the World Health Organization (WHO) Alcohol,
Smoking, and Substance Involvement Screening Test. Data gathered during brief
interventions were analyzed using grounded theory strategies to identify barriers
patients believed inhibited drug use behavior change. Numerous perceived barriers
to drug use behavior change were identified. Study implications and limitations
are discussed.
PMID- 24354548
TI - Metabolomics: a potential powerful ally in the fight against cancer.
PMID- 24354549
TI - Characteristics of patients misdiagnosed with Alzheimer's disease and their
medication use: an analysis of the NACC-UDS database.
AB - BACKGROUND: This study compared individuals whose clinical diagnosis of
Alzheimer's disease (AD) matched or did not match neuropathologic results at
autopsy on clinical and functional outcomes (cognitive impairment, functional
status and neuropsychiatric symptoms). The study also assessed the extent of
potentially inappropriate medication use (using potentially unnecessary
medications or potentially inappropriate prescribing) among misdiagnosed
patients. METHODS: Longitudinal data from the National Alzheimer's Coordinating
Center Uniform Data Set (NACC-UDS, 2005-2010) and corresponding NACC
neuropathological data were utilized to compare 88 misdiagnosed and 438
accurately diagnosed patients. RESULTS: Following adjustment of sociodemographic
characteristics, the misdiagnosed were found to have less severe cognitive and
functional impairment. However, after statistical adjustment for
sociodemographics, dementia severity level, time since onset of cognitive decline
and probable AD diagnosis at baseline, the groups significantly differed on only
one outcome: the misdiagnosed were less likely to be depressed/dysphoric. Among
the misdiagnosed, 18.18% were treated with potentially inappropriate medication.
An additional analysis noted this rate could be as high as 67.10%. CONCLUSIONS:
Findings highlight the importance of making an accurate AD diagnosis to help
reduce unnecessary treatment and increase appropriate therapy. Additional
research is needed to demonstrate the link between potentially inappropriate
treatment and adverse health outcomes in misdiagnosed AD patients.
PMID- 24354551
TI - Autobiography of Terry A. Miller.
PMID- 24354550
TI - Preface to the Terry A. Miller Festschrift.
PMID- 24354554
TI - Supratentorial cortical ependymoma: case series and review of the literature.
AB - Supratentorial cortical ependymoma (CE), a rare type of ependymoma, is located in
the superficial cortex. We reported 11 patients (six female and five male) with
CE. The age of the patients ranged from 2 to 63 years old with a median age of 47
years at the time of diagnosis. On MRI, enhancement was noted in all cases with
solid appearance in six cases, and solid and cystic appearance in five cases. The
frontal and parietal regions were the most common locations for CE. On histology,
two were low-grade (WHO grade II) and nine were WHO grade III anaplastic
ependymomas. Some tumors exhibited clear cell, spindle (tanycytic) and giant cell
morphologies, as well as the classic ependymoma morphology. Dura-based tumor
nodules and even tumor dissemination along the dura can be seen in CEs. Low grade
CEs have a higher likelihood to present with seizures, a lower likelihood to
cause brain edema, tumor recurrence and lower mortality than anaplastic
ependymomas. While difficult, anaplastic CEs may be distinguished from
glioblastoma by a clear interface between tumor and adjacent brain tissue,
relative uniformity of tumor cell nuclei and immunopositivity for epithelial
membrane antigen and/or CD99. As is the case for ependymomas in general, gross
total resection is still the treatment of choice for CEs.
PMID- 24354555
TI - Cutaneous epithelioid hemangioendothelioma presented as an ulcerated areolar
mass.
PMID- 24354556
TI - New method for the extraction of volatile lipid oxidation products from shrimp by
headspace-solid-phase microextraction-gas chromatography-mass spectrometry and
evaluation of the effect of salting and drying.
AB - A new method based on headspace-solid-phase microextraction (HS-SPME) and gas
chromatography-mass spectrometry (GC-MS) was developed, aimed at evaluating the
formation of volatile lipid oxidation products (VLOPs) in shrimp during the
salting and drying process. Of the four fibers evaluated, the fiber coated with
divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) was the most adequate
for the quantification of the VLOPs. The best analytical conditions were obtained
by homogenization in an ultraturrax followed by extraction at 40 degrees C for
30 min. The optimized method allowed for the rapid and simple extraction of the
VLOPs, with low detection (<=0.15 ng g(-1)) and quantification (<=0.50 ng g(-1))
limits and satisfactory precision (<=12.67%) and extraction efficiency
(>=94.28%). The salting and drying negatively affected shrimp quality, reducing
the fatty acid content and increasing the VLOPs, especially hexanal.
PMID- 24354557
TI - Formation and Direct Repair of UV-induced Dimeric DNA Pyrimidine Lesions.
AB - Direct repair of UV-induced DNA lesions represents an elegant method for many
organisms to deal with these highly mutagenic and cytotoxic compounds. Although
the participating proteins are structurally well investigated, the exact repair
mechanism of the photolyase enzymes remains a vivid subject of current research.
In this review, we summarize and highlight the recent contributions to this
exciting field.
PMID- 24354558
TI - Health literacy and health-promoting behaviors among multiethnic groups of women
in Taiwan.
AB - OBJECTIVE: To understand the current status of health literacy and the
relationship between health literacy and health-promoting behaviors among
multiethnic groups of women in Taiwan. DESIGN: Convenience and snowball sampling
methods were used to recruit study participants. Data were collected using a
cross-sectional questionnaire survey. SETTING: We recruited community female
adults who lived in greater Taipei or Taoyuan areas (northern Taiwan) from
January 1, 2010 through June 30, 2011. PARTICIPANTS: A total of 378 female
participants were contacted, of which 351 consented to participate and 347
completed valid questionnaires for analysis. METHODS: Health literacy was
measured with the Taiwan Health Literacy Scale, and health-promoting behaviors
were measured by the Chinese version of the Health-Promoting Lifestyle Profile.
RESULTS: Participants had a moderate level of health literacy, and one third of
them had inadequate health literacy. Participants with inadequate health literacy
were more likely to be younger, not a high school graduate, and Vietnamese; to
have a low monthly family income and no diagnosed diseases; to use a second
language; and to regard TV/radio as the most useful source of health information.
Health literacy alone could significantly predict health-promoting behaviors
among the participants. CONCLUSIONS: Our findings confirmed that low health
literacy is prevalent among underprivileged women in Taiwan. Health-related
programs that are literacy sensitive and culturally appropriate are needed to
teach and encourage health-promoting behaviors.
PMID- 24354562
TI - Emerging drugs for biliary cancer.
AB - INTRODUCTION: The number of biliary cancer patients is small and it is often
complicated by serious adverse events making it difficult for clinical studies to
be performed on this cancer. However, researches for clarification of the
mechanisms of onset and proliferation of biliary cancer and of the effects of
drugs suppressing these mechanisms have been initiated recently, with the goal of
establishing effective treatments. AREAS COVERED: This review will cover
epidemiological and biological features of biliary cancer, the efficacy and
limitations of the existing methods of treatment, and current goals for the
development of new treatment methods. Furthermore, the findings of pre-clinical
studies on promising treatment targets and ongoing clinical studies are also
reviewed, and perspectives for the future of treatment are discussed. EXPERT
OPINION: Following the recent increase in the interest in drug development,
attempts at clarifying the molecular mechanisms underlying the onset and
proliferation have been made proactively, accompanied by clinical studies on
various molecular-targeted drugs for the treatment of this cancer. To demonstrate
the efficacy of these drugs, it is essential to establish a system for efficient
screening of patients carrying the molecular targets and to devise an excellent
clinical study design.
PMID- 24354561
TI - Two-component systems in Streptomyces: key regulators of antibiotic complex
pathways.
AB - Streptomyces, the main antibiotic-producing bacteria, responds to changing
environmental conditions through a complex sensing mechanism and two-component
systems (TCSs) play a crucial role in this extraordinary "sensing"
device.Moreover, TCSs are involved in the biosynthetic control of a wide range of
secondary metabolites, among them commercial antibiotics. Increased knowledge
about TCSs can be a powerful asset in the manipulation of bacteria through
genetic engineering with a view to obtaining higher efficiencies in secondary
metabolite production. In this review we summarise the available information
about Streptomyces TCSs, focusing specifically on their connections to antibiotic
production.
PMID- 24354563
TI - Determinants of systolic blood pressure response during exercise in overweight
subjects.
AB - AIM: Higher systolic exercise blood pressure (BP) is associated with increased
cardiovascular risk in hypertension. We aimed at identifying covariates of
systolic exercise BP in overweight subjects. METHODS: 77 subjects with body mass
index (BMI) > 27 kg/m(2) and without known heart disease were tested. BP was
measured by sphygmomanometry before and at all exercise stages during maximal
exercise capacity testing on a treadmill. High peak systolic exercise BP was
defined as >= 200 mmHg. RESULTS: The study population was 48 +/- 10 years and
included 60% women and 42% with known hypertension. Average BMI was 32.6 +/- 4.8
kg/m(2) and clinic BP 132/82 +/- 17/8 mmHg. High systolic exercise BP was found
in 32%. Subjects with high systolic exercise BP had higher systolic clinic and 24
h ambulatory BP (ABP), as well as lower peak oxygen uptake, compared with
subjects with normal systolic exercise BP (all p < 0.05). In multiple regression
analysis known hypertension (beta = 0.33), higher systolic ABP (beta = 0.22) and
high-density lipoprotein (HDL)-cholesterol level (beta = 0.23, all p < 0.05)
predicted higher systolic exercise BP independent of sex and peak oxygen uptake
(multiple R(2) = 0.32, p < 0.001). CONCLUSION: Among overweight subjects, known
hypertension, higher systolic ABP and HDL-cholesterol level were the most
important factors predicting higher systolic exercise BP.
PMID- 24354564
TI - Herpes zoster infection associated with acute coronary syndrome: a population
based retrospective cohort study.
AB - BACKGROUND: Vasculopathy in varicella zoster virus (VZV) infection and a proposed
association between herpes virus infection and atherosclerosis suggest a possible
link between VZV infection and vascular thrombosis. OBJECTIVES: To determine the
risk of acute coronary syndrome (ACS) associated with herpes zoster infection.
METHODS: We used the Taiwan National Health Insurance Research Database to
identify 57,958 patients newly diagnosed with herpes zoster between 1999 and
2010; 231,832 patients without herpes zoster were examined as the control group.
Both cohorts were followed up until the end of 2010 to measure the incidence of
ACS. Cox proportional-hazards regression and Kaplan-Meier analyses were used to
measure the hazard ratios (HR) and the cumulative incidences of ACS,
respectively. RESULTS: The incidence of ACS was 1.24-fold higher in the herpes
zoster group than in the control group [36.8 vs. 29.6 per 10,000 person-years,
95% confidence interval (CI) 1.16-1.33]. After adjusting for age, sex and
comorbidities, the HR of ACS for the herpes zoster group compared with the
control group was 1.15 (95% CI 1.07-1.24). Analysis by the time lag (<= 3 months,
<= 1 year, > 1 year) showed that the incidence of ACS remained significantly
higher in the herpes zoster group than in the control group, with an adjusted HR
of 1.10 (95% CI 1.02-1.19) after the 1-year follow-up period. The Kaplan-Meier
survival curve showed that the risk of ACS was significantly higher in the herpes
zoster group than in the control group (P < 0.001). CONCLUSION: Herpes zoster
infection is associated with an increased risk of ACS.
PMID- 24354566
TI - Physical and mental quality of life in adult patients with haemophilia in
Belgium: the impact of financial issues.
AB - In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on
patients' quality of life (QoL) is scarce. This project aims to assess physical
and mental QoL (P-QoL and M-QoL) simultaneously, and to analyse the influence of
different variables on these two aspects of QoL. After Ethics Committee approval,
we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without
current inhibitors, on replacement therapy (on-demand or secondary prophylaxis),
regularly followed up at our comprehensive treatment centre. Seventy-one (n = 59
HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL
assessment forms. We analysed two groups of variables: one including variables
previously associated with decreased QoL, and another including variables with
unclear impact on QoL (e.g., patients' understanding of haemophilia-related
issues, economical concerns). In our population (mean +/- SD age: 45.2 +/- 14.7
years old), P-QoL appeared more reduced than M-QoL. P-QoL was strongly influenced
by the number of arthropathies while M-QoL was primarily affected by patients'
concern of personal costs due to haemophilia. Among this latter group, having
knowledge of insurance coverage had a positive impact on M-QoL. Scores did not
depend on haemophilia type. QoL was impaired in our haemophilia patients. A
simultaneous assessment of P-QoL and M-QoL confirmed the benefit of primary
prophylaxis in P-QoL, while originally pointing out the major burden of patients'
concerns and poor understanding of haemophilia-related economical issues on their
M-QoL. This might become a particularly challenging issue in times of financial
crisis.
PMID- 24354565
TI - Computational studies of the regioselectivities of COMT-catalyzed meta-/para-O
methylations of luteolin and quercetin.
AB - Catechol-O-methyltransferase (COMT, EC 2.1.1.6) plays a central role in the
inactivation of neurotransmitters sharing a catecholic motif by transferring a
methyl group from AdoMet. Methylation of the meta-hydroxyl is much more common
than that of the para-hydroxyl in many COMT substrates, such as dopamine and
norepinephrine. Our experimental data showed that quercetin preferred meta
methylation but luteolin favored a para-methylation. To elucidate the mechanism
for different preferences of methylations of quercetin and luteolin, we performed
a theoretical investigation on the different regioseletivities of COMT-catalyzed
methylations for quercetin and luteolin by a combined approach of MD simulations,
ab initio calculations, and QM/MM computations. The ab initio calculation results
showed that both quercetin and luteolin have more negative charge distributions
on the meta-O atom than the para-O atom, which indicated that meta-O preferred
SN2 reaction for their methylation. Our QM/MM computations also confirmed that
these two flavonoids have lower reaction energetic barriers for COMT-catalyzed
meta-O-methylation than para-O-methylation. On the other hand, our binding free
energy computation results indicated that quercetin has a more stable binding
mode for meta-O-methylation than para-O-methylation but luteolin has a more
stable binding mode for para-O-methylation than meta-O-methylation. We gave a
comprehensive explanation considering both thermodynamics and reaction kinetics
aspects and discussed the protein-inhibitor interactions as well as the O
methylation mechanism in our present work.
PMID- 24354567
TI - Long-term retrospective evaluation of short implants in the posterior areas:
clinical results after 10-12 years.
AB - AIM: To evaluate the long-term clinical results of short implants in the
posterior areas and analyse the possible influence of different variables on
implant success rate and marginal bone loss (MBL). METHODS: A retrospective study
design was used. Patients were included if they had received one or more short
implants (<=8.5 mm long) in the posterior jaws at least 10 years earlier. All
implants were embedded in plasma rich in growth factors (PRGF). The cumulative
success rate was the primary outcome. MBL and the influence of different
variables as secondary outcomes were assessed. RESULTS: A total of 111 short
implants (7.0, 7.5 and 8.5 mm in length) placed in 75 patients met the inclusion
criteria. Of which, 94 were splinted to longer ones. The mean follow-up was 123.3
months (SD = 10.4 months). The mean crown-implant ratio was 1.4 (SD = 0.3). The
mean MBL was 1.0 mm at mesial (SD = 0.7) and 0.9 mm (SD = 0.6) at distal aspect.
One short implant failed. Success rate was 98.9% and 98.2% for the implant and
patient-based analysis respectively. No relationship was observed between the
studied variables and the MBL. CONCLUSIONS: These clinical results support the
use of short implants as an effective and safe long-term treatment option.
PMID- 24354568
TI - Photogenerated charge carriers and reactive oxygen species in ZnO/Au hybrid
nanostructures with enhanced photocatalytic and antibacterial activity.
AB - Semiconductor nanostructures with photocatalytic activity have the potential for
many applications including remediation of environmental pollutants and use in
antibacterial products. An effective way for promoting photocatalytic activity is
depositing noble metal nanoparticles (NPs) on a semiconductor. In this paper, we
demonstrated the successful deposition of Au NPs, having sizes smaller than 3 nm,
onto ZnO NPs. ZnO/Au hybrid nanostructures having different molar ratios of Au to
ZnO were synthesized. It was found that Au nanocomponents even at a very low
Au/ZnO molar ratio of 0.2% can greatly enhance the photocatalytic and
antibacterial activity of ZnO. Electron spin resonance spectroscopy with spin
trapping and spin labeling was used to investigate the enhancing effect of Au NPs
on the generation of reactive oxygen species and photoinduced charge carriers.
Deposition of Au NPs onto ZnO resulted in a dramatic increase in light-induced
generation of hydroxyl radical, superoxide and singlet oxygen, and production of
holes and electrons. The enhancing effect of Au was dependent on the molar ratio
of Au present in the ZnO/Au nanostructures. Consistent with these results from
ESR measurements, ZnO/Au nanostructures also exhibited enhanced photocatalytic
and antibacterial activity. These results unveiled the enhanced mechanism of Au
on ZnO and these materials have great potential for use in water purification and
antibacterial products.
PMID- 24354570
TI - Improving clinical research on continuous positive airway pressure.
PMID- 24354571
TI - Interpreting regional differences in neonatal outcomes for extremely preterm
babies.
PMID- 24354572
TI - Growth charts and long-term sequelae in extreme preterm infants--from full-term
age to 10 years.
AB - AIM: To describe growth pattern from full-term age to 10 years in infants born
before 26 weeks of gestation. METHOD: This retrospective longitudinal cohort
contained 123 children from Karolinska Hospital, Stockholm, during 1990-2002.
Length/height (Ht), weight (Wt) and head circumference (HC) were recorded monthly
during the first year, every 3 months until 2 years and yearly thereafter, but HC
at 15 months and at median age of 8.1/9.7 years (range 2-14) in boys/girls.
RESULTS: For boys/girls at birth, the mean Z-score for Ht was -0.2/-0.2, for Wt
0.0/-0.2 and for HC 0.0/-0.3. At term, the mean Z-score for Ht was -3.8/-3.1, for
Wt -3.0/-2.5 and for HC -1.7/-1.2. At 1 year, the mean Z-score for Ht was-1.3/
1.3, for Wt -1.9/-1.7 and for HC -1.2/-1.0. At 2 years, the mean Z-score for Ht
was -1.3/-1.1, for Wt -1.6/-1.2 and at 10 years for Ht -0.7/-0.4; that was on
average -0.3 below mid-parental height; for Wt -0.2/-0.2. Long-term sequelae were
found in 48% of the boys and 34% of the girls. CONCLUSION: By 10 years of age,
the attained mean Ht was in accordance with their genetic potential and almost
half of these children had significant long-term sequelae.
PMID- 24354573
TI - Bone mineral density in Turner's syndrome and the influence of pubertal
development.
AB - AIM: To describe bone mineral density at the lumbar spine in a group of girls
with Turner's syndrome and determine its relation to pubertal development.
METHODS: Girls with Turner's syndrome aged over 12 years were invited to
participate in the study. All participants underwent auxology, pubertal
assessment and laboratory evaluation. Bone mineral density was estimated by dual
energy X-ray absorptiometry. Bone mineral apparent density was then calculated,
and the results were compared with age-matched Dutch reference data. RESULTS: We
studied 32 girls with Turner's syndrome, mean (SD) [range] age 16.7 (2.6) [12.4
20.2] years and height 148.3 (9.0) [126-159.2] cm. Bone mineral apparent density
lumbar spine values were -0.87 SD, significantly lower than in the reference
population (p <0.001). Bone mineral apparent density values were positively and
significantly associated with breast Tanner stages and postmenarcheal status, but
not spontaneous puberty. However, no significant association was found between
bone mineral apparent density and karyotype, growth hormone or timing of
oestrogen therapy. CONCLUSION: Girls with Turner's syndrome have lower bone
mineral apparent density values at the lumbar spine, even after correcting for
size, compared with an age- and sex-matched general population. Pubertal
development has significant impact on bone mineral apparent density in girls with
Turner's syndrome.
PMID- 24354574
TI - The incretin effect does not differ in trained and untrained, young, healthy men.
AB - AIM: After both oral and intravenous glucose administration, peripheral insulin
concentrations are lower in trained compared with untrained humans. Part of this
is explained by an adaptation within the beta-cell. The insulin secretion rate is
higher after oral compared with intravenous glucose administration due to the
release of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic
polypeptide (GIP) enhancing the glucose-induced insulin secretion (the incretin
effect). Our aim was to investigate whether GIP or GLP-1 release or the incretin
effect was different in trained compared with untrained humans after oral and
intravenous glucose administration. METHODS: A 31/2-h oral glucose tolerance test
was performed in eleven trained and ten untrained, young, healthy men. On a
separate day, an isoglycaemic intravenous glucose infusion was performed matching
the individual glucose concentrations obtained during the oral glucose tolerance
test. Blood samples for insulin, C-peptide, GIP and GLP-1 analyses were obtained
frequently during both tests, and the insulin secretion rate, incretin effect and
insulin clearance were calculated. RESULTS: Plasma GIP and GLP-1 concentrations,
the incretin effect and the insulin clearance did not differ, and plasma glucose,
insulin and C-peptide concentrations and the insulin secretion rate were lower in
trained compared with untrained subjects during both tests. CONCLUSION: With no
difference in incretin effect and insulin clearance between the two groups, the
lower plasma insulin concentrations found in trained compared with untrained,
young, healthy men are most likely explained by lower beta-cell sensitivity to
glucose and enhanced glucose uptake in skeletal muscle in the former group.
PMID- 24354575
TI - Systematic review and meta-analysis on outcomes for endoscopic versus external
dacryocystorhinostomy.
AB - BACKGROUND: Dacryocystorhinostomy (DCR) is commonly performed for epiphora,
dacryocystitis and during tumor surgery. External (EXT-DCR) and endoscopic DCR
(END-DCR) are both practiced. END-DCR was initially performed with laser (EL-DCR)
but has shifted to careful bone removal with mechanical drills (EM-DCR). High
level evidence from comparative cohorts was sought to compare outcomes. METHOD:
Medline (1966 - January 28th, 2013) and Embase (1980 - January 28(th), 2013) were
searched for comparative studies (RCT/cohorts) of END-DCR to EXT-DCR for acquired
nasolacrimal duct (NLD) obstruction. Primary outcome was DCR success, defined as
resolution of symptoms and/or patent NLD on irrigation or dacroscintography.
Secondary outcomes were scarring, infection and post-operative bleeding. Meta
analysis was performed with the Mantel-Haenszel Method and presented as Risk
Ratios (RR) with Confidence Intervals (CI). RESULTS: The search identified 3582
studies and 355 were reviewed after screening. Full text review yielded 19
studies (4 RCTs and 15 cohorts). Overall, EXT-DCR had slightly better success
rates than END-DCR (RR 0.96, CI 0.93-1.00). However, EM-DCR outcomes were
comparable to EXT-DCR (RR 1.02, CI 0.98-1.06), whereas EL-DCR had poorer outcomes
(RR 0.85, CI 0.79-0.91) when compared separately. The RR for scarring, bleeding
and infection with END-DCR versus EXT-DCR was 0.07 (CI 0.02-0.22), 0.72 (CI 0.46
1.13) and 0.24 (CI 0.11- 0.54), respectively. The rates of reported revision
surgery were similar. CONCLUSION: DCR is a procedure with high success rates.
Endoscopic procedures differ greatly by technique with EM-DCR offering comparable
results to EXT-DCR, without the risk of cosmetically unacceptable scars.
PMID- 24354576
TI - Role of fibroblast growth factors in elicitation of cell responses.
AB - Fibroblast growth factors (FGFs) are signalling peptides that control important
cell processes such as proliferation, differentiation, migration, adhesion and
survival. Through binding to different types of receptor on the cell surface,
these peptides can have different effects on a target cell, the effect achieved
depending on many features. Thus, each of the known FGFs elicits specific
biological responses. FGF receptors (FGFR 1-5) initiate diverse intracellular
pathways, which in turn lead to a variety of results. FGFs also bind the range of
FGFRs with a series of affinities and each type of cells expresses FGFRs in
different qualitative and quantitative patterns, which also affect responses. To
summarize, cell response to binding of an FGF ligand depends on type of FGF, FGF
receptor and target cell, all interacting in concert. This review aims to examine
properties of the FGF family and its members receptors. It also aims to summarize
features of intracellular signalling and highlight differential effects of the
various FGFs in different circumstances.
PMID- 24354577
TI - Bovine thoracoscopy: surgical technique and normal anatomy.
AB - OBJECTIVE: To describe a surgical technique for thoracoscopy and report visible
anatomy within the thoracic cavity of standing cattle. STUDY DESIGN: Prospective
study. ANIMALS: Adult clinically healthy Holstein-Friesian cows (n = 15).
METHODS: Each cow had four thoracoscopic examinations. Initially, the left
hemithorax was examined after passive lung collapse, then again 24 hours later
after CO2 insufflation. The right hemithorax was examined 24 hours later after
passive lung collapse and again 24 hours later after CO2 insufflation. RESULTS:
CO2 insufflation did not significantly improve visibility within the pleural
space. Collapsed lung, aorta, esophagus, diaphragm, and azygos vein were readily
viewed; however, the pericardial region was not consistently visible. Minor
laceration of the lung occurred in 1 cow with adhesions, otherwise there were no
intra- or postoperative complications. All cows recovered without signs of
discomfort. No local swelling or emphysema occurred at the portals. CONCLUSIONS:
Thoracoscopy can be safely performed on healthy standing cattle.
PMID- 24354578
TI - The association of circulating angiogenic factors and HbA1c with the risk of
preeclampsia in women with preexisting diabetes.
AB - OBJECTIVE: To assess whether glycemic control, soluble fms-like tyrosine kinase 1
(sFlt1) and placental growth factor (PlGF) were associated with the development
of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting
diabetes. METHODS: Maternal circulating angiogenic factors (sFlt1 and PlGF)
measured on automated platform were studied at four time points during pregnancy
in women with diabetes (N = 159) and reported as multiples of the median (MOM) of
sFlt1/PlGF ratio (median, 25th-75th percentile) noted in non-diabetic non
hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was
determined by review of de-identified clinical data. RESULTS: PE developed in 12%
(N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among
diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35-40 weeks was
threefold higher than in non-diabetic controls [MOM 3.21(1.19-7.24), p = 0.0001].
Diabetic women who subsequently developed PE had even greater alterations in
sFlt1/PlGF ratio during the third trimester [MOM for PE at 27-34 weeks 15.18
(2.37-26.86), at 35-40 weeks 8.61(1.20-18.27), p <= 0.01 for both windows
compared to non-diabetic controls]. Women with diabetes who subsequently
developed GHTN also had significant alterations in angiogenic factors during
third trimester; however, these findings were less striking. Among women with
diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher
in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic
PE vs diabetic non-PE). CONCLUSIONS: Women with diabetes had a markedly altered
anti-angiogenic state late in pregnancy that was further exacerbated in subjects
who developed PE. Altered angiogenic factors may be one mechanism for the
increased risk of PE in this population. Increased HbA1c in the first trimester
of pregnancies in women with diabetes was strongly associated with subsequent PE.
PMID- 24354579
TI - The effect of prosthetic feedback on the strategies and synergies used by
vestibular loss subjects to control stance.
AB - BACKGROUND: This study investigated changes in stance movement strategies and
muscle synergies when bilateral peripheral vestibular loss (BVL) subjects are
provided feedback of pelvis sway angle. METHODS: Six BVL (all male) and 7 age
matched male healthy control (HC) subjects performed 3 stance tasks: standing
feet hip width apart, eyes closed, on a firm and foam surface, and eyes open on
foam. Pelvis and upper trunk movements were recorded in the roll and pitch
planes. Surface EMG was recorded from pairs of antagonistic muscles at the lower
leg, trunk and upper arm. Subjects were first assessed without feedback. Then,
they received training with vibrotactile, auditory, and fall-warning visual
feedback during stance tasks before being reassessed with feedback. RESULTS:
Feedback reduced pelvis sway angle displacements to values of HCs for all tasks.
Movement strategies were reduced in amplitude but not otherwise changed by
feedback. These strategies were not different from those of HCs before or after
use of feedback. Low frequency motion was in-phase and high frequency motion anti
phasic. Feedback reduced amplitudes of EMG, activity ratios (synergies) of
antagonistic muscle pairs and slightly reduced baseline muscle activity.
CONCLUSIONS: This is the first study demonstrating how vestibular loss subjects
achieve a reduction of sway during stance with prosthetic feedback. Unchanged
movement strategies with reduced amplitudes are achieved with improved
antagonistic muscle synergies. This study suggests that both body movement and
muscle measures could be explored when choosing feedback variables, feedback
location, and patient groups for prosthetic devices which reduce sway of those
with a tendency to fall.
PMID- 24354580
TI - A rectal bleeding algorithm can successfully reduce emergency admissions.
AB - AIM: Acute lower gastrointestinal bleeding (LGIB) is a common cause of emergency
admissions yet rarely requires blood transfusion or radiological/surgical
intervention. We aimed to develop a risk assessment tool to identify patients
with acute LGIB who can be safely managed in primary care. METHOD: We
retrospectively applied an existing nomogram to 20 admissions to obtain criteria
that could predict the need for transfusion. We simplified the algorithm to three
criteria and developed an associated care pathway. If haemoglobin was > 13 g/dl,
systolic blood pressure > 115 mmHg and the patient was not anticoagulated,
admission could be avoided. These criteria were then applied to 57 prospective
patients attending during a 16-week period. This was implemented with education
of primary and secondary care staff, access to an emergency clinic and provision
of patient information. RESULTS: We applied our algorithm and care pathway to 57
patients with uncomplicated rectal bleeding. Thirty-five per cent (20/57) of
potential admissions were avoided. Instead, patients received written information
and underwent flexible sigmoidoscopy as outpatients within 6 weeks. One
discharged patient was readmitted from endoscopy with severe colitis. There were
no other readmissions or complications. Of the 36 patients for whom the algorithm
predicted admission was needed, 33% (12/36) were anticoagulated, 94% (34/36) had
haemoglobin < 13 g/dl and 42% (15/36) had a systolic blood pressure < 115 mmHg.
Only one admission (1.8%) did not fulfil the admission criteria and could have
potentially been avoided. Avoidable admissions reduced from 50 to 1.8%.
CONCLUSION: The application of a simple rectal bleeding algorithm can safely
prevent unnecessary admissions.
PMID- 24354581
TI - FXIII: mechanisms of action in the treatment of hemophilia A.
AB - BACKGROUND: Hemophilia is characterized by abnormal thrombin generation and
impaired clot stability. FXIII promotes clot stability and may be a useful
adjunct treatment for hemophilia. OBJECTIVES: This study examined the clot
stabilizing effects and safety of supra-physiological FXIII and explored the
mechanisms via which FXIII exerts its effects in hemophilia A. METHODS: The
effects of FXIII on clot formation and stability were examined using a
thromboelastometry assay and blood samples collected from six patients with
severe hemophilia A. The effect of FXIII on clot formation was also assessed
using a murine model. The mechanisms of FXIII action in hemophilia A were
explored by measuring thrombin generation, rates of FXIII activation and effects
on clot permeability, pore size and fibrin fiber diameter. RESULTS: This study
demonstrates that supra-physiological concentrations of FXIII stabilize clots in
blood from patients with hemophilia by improving resistance to t-Pa-induced
fibrinolysis even at low concentrations of FVIII (FVIII< 0.1 IU mL-1, P < 0.05,
anova). Addition of FXIII stoichiometrically up-regulates its activation,
correcting the fibrin clot structure, reducing clot permeability and facilitating
thrombin generation; FXIII significantly shortens ttPeak and lagtime (P < 0.05)
in FVIII-deficient plasma, providing a novel explanation for its positive effects
on clot stability and structure. The murine model indicates that supra
physiological FXIII is tolerated and does not significantly alter time to clot
formation. CONCLUSION: The effects of FXIII on clot stability and physical clot
structure are seen at low concentrations of FVIII, indicating that FXIII could be
a useful treatment in a variety of clinical scenarios.
PMID- 24354582
TI - Late onset GM2 gangliosidosis presenting with motor neuron disease: an autopsy
case.
AB - Adult-onset GM2 gangliosidosis is very rare and only three autopsy cases have
been reported up to now. We report herein an autopsy case of adult-onset GM2
gangliosidosis. The patient developed slowly progressive motor neuron disease
like symptoms after longstanding mood disorder and cognitive dysfunction. He
developed gait disturbance and weakness of lower limbs at age 52 years. Because
of progressive muscle weakness and atrophy, he became bed-ridden at age 65. At
age of 68, he died. His neurological findings presented slight cognitive
disturbance, slight manic state, severe muscle weakness, atrophy of four limbs
and no extrapyramidal signs and symptoms, and cerebellar ataxia.
Neuropathologically, mild neuronal loss and abundant lipid deposits were noted in
the neuronal cytoplasm throughout the nervous system, including peripheral
autonomic neurons. The most outstanding findings were marked neuronal loss and
distended neurons in the anterior horn of the spinal cord, which supports his
clinical symptomatology of lower motor neuron disease in this case. The presence
of lipofuscin, zebra bodies and membranous cytoplasmic bodies (MCB) and the
increase of GM2 ganglioside by biochemistry led to diagnosis of GM2
gangliosidosis.
PMID- 24354583
TI - Managing medications: the role of informal caregivers of older adults and people
living with dementia. A review of the literature.
AB - AIMS AND OBJECTIVES: To explore published literature that describes what is known
about the role of informal caregivers as they manage medications for older adults
and/or people living with dementia residing in the community. BACKGROUND: The
number of informal caregivers of older adults, including people living with
dementia, is growing worldwide. Good medication management by informal caregivers
contributes to improved health outcomes and reduced institutionalisations for the
care recipient; however, little is known about this domain of care. DESIGN:
Narrative review. METHODS: A literature search was conducted to identify relevant
research articles written in English between January 2000-April 2013, sourced
from online database searches using multiple keywords, reviewing reference lists
and citations of key articles and Internet searches. Articles were included if
they described informal caregiver medication management for older adults and/or
people living with dementia. RESULTS: Ten articles were found that described this
role from the perspective of the informal caregiver. The evidence suggests that
this role is complex and is often made more difficult because of increasing
medication regimen complexities, aspects of the relationship between the
caregiver and the care recipient, healthcare system practices and a lack of
information and/or training available to the informal caregiver, especially when
caring for people living with dementia. CONCLUSION: Responsibility for managing
medications for older adults and/or people living with dementia in the community
often falls to informal caregivers. More information resources are required for
this role, which requires specific medication management skills and knowledge and
is further complicated by the cognitive decline of the care recipient. RELEVANCE
TO CLINICAL PRACTICE: Informal caregivers are often expected to manage
medications in a safe and effective manner for their older care recipient, who
may also have cognitive impairment. Nurses, who may be in frequent contact with
community-living older adults/people living with dementia, can be an important
source of information, training and support for informal caregivers.
PMID- 24354584
TI - Beneficial effects of traditional Chinese medicine on the treatment of
osteoporosis on ovariectomised rat models.
AB - Osteoporosis is a metabolic bone disorder that affects both men and women
worldwide. It causes low bone mass and therefore increases bone susceptibility to
fracture when bone undergoes a minor trauma. Lack of estrogen is the principal
cause of osteoporosis. Estrogen, calcium, calcitonin, vitamin D and several
antioxidants help in the prevention of osteoporosis. In order to effectively
treat osteoporosis, there has been an extended research on the biological
activities of traditional medicines since synthetic medicines possess several
side effects that reduce their efficacy. Therefore, there is a need to develop
new treatment alternatives for osteoporosis. This review centres on the
scientific researches carried out on the evaluation of Chinese traditional
medicines in the treatment of osteoporosis. Various plants like Achyranthes
bidentata, Davallia formosana, polygonatum sibiricum, Cibotium barometz, Er-Zhi
Wan, Curculigo orchioides and a combined treatment of Hachimi-jio-gan (Ba-Wei-Di
Huang-Wan) with alendronate proved active in preventing post-menopausal
osteoporosis.
PMID- 24354585
TI - Bone metabolism and histomorphometric changes in murine models treated with
sclerostin antibody: a systematic review.
AB - Preventing osteoporotic fractures in millions of individuals may significantly
reduce the associated morbidity and health-care expenditures incurred. As such,
the search for newer anti-osteoporotic agents has been ongoing for years. Genetic
studies have proven that the secreted protein sclerostin is one of the main
culprits, which negatively regulates the bone formation. Recently, sclerostin
neutralizing monoclonal antibodies (Scl-Ab) in rodent studies have shown positive
effects on bone homeostasis. An extensive search of the literature was performed
in the BIOSIS, Cinahl, EMBASE, Pub- Med, Web of Science and Cochrane Library
databases to evaluate the published murine studies on the effects of Scl-Ab on
the bone metabolism and histomorphometric parameters. Our systematic review
depicts a significant association between Scl-Ab administration and improvement
in bone formation, bone density, bone volume and trabecular thickness.
PMID- 24354586
TI - Osteoporotic fracture healing: potential use of medicinal plants from the
tropics.
AB - With improvements in living standards and healthcare, life expectancy has been
increasing dramatically in most parts of the world. These situations lead to the
increase in the reported cases of geriatrics-related diseases such as hypogonadal
osteoporosis with skeletal fracture being the ultimate outcome, which eventually
causes significant morbidity and mortality. The deficient gonadal hormones, which
are the main cause of hypogonadal osteoporosis, could be substituted with hormone
replacement therapy to hinder bone loss. However, the artificial hormonal therapy
has been linked to grievous conditions such as breast and prostate cancers. In
view of the various adverse effects associated with conventional treatment, many
researchers are now focusing on finding alternative remedies from nature. This
article explores the possibilities of certain medicinal plants native to Malaysia
that possess androgenic and antioxidant properties to potentially be used in the
treatment of fracture due to osteoporosis in ageing people.
PMID- 24354587
TI - Can soy prevent male osteoporosis? A review of the current evidence.
AB - The Asian population whose soy intake is higher compared to Western populations
shows a significantly lower incidence of osteoporotic fracture. Several meta
analyses have revealed that supplementation of soy isoflavones improve bone
health status in women. This review examined the current evidence as to whether
soy could exhibit similar bone protective effects on the male population. In vivo
studies revealed that supplementation of soy protein or soy isoflavones improved
bone health in both normal and osteoporotic male rodents. Cell culture studies
showed that soy isoflavones influenced osteogenesis and osteoclastogenesis
through mechanisms such as estrogen receptor binding activity, antiinflammatory
activity and anti-parathyroid hormone activity. Soy isoflavones also affected
calcium channel signaling and might exhibit direct effects on the
osteoblastogenesis modulator, core binding factor 1. However, limited clinical
trials involving soy intervention in males generally showed insignificant
results. This could be attributed to the short duration of intervention,
characteristics of the subjects or method of bone health assessment. More well
planned clinical trials are required to establish possible bone protective
effects of soy in men.
PMID- 24354588
TI - Rationale and design of the costs, health status and outcomes in community
acquired pneumonia (CHO-CAP) study in elderly persons hospitalized with CAP.
AB - BACKGROUND: Vaccine effectiveness is usually determined in randomized controlled
trials (RCT) and if effective, additional information, e.g. on cost
effectiveness, is required to allow evidence-based decision making. A
prerequisite for proper health economic modelling is the availability of good
quality data on health care resources use, health outcomes and quality-of-life
(QoL) data. The "Collecting health outcomes and economic data on hospitalized
Community Acquired Pneumonia (CHO-CAP)--a prospective cohort study" is executed
alongside the Community Acquired Pneumonia Immunization Trial with Adults (CAPiTA
trial) to capture health outcomes and economic data of elderly hospitalized with
CAP and matched controls without CAP. METHODS/DESIGN: CAPiTA is a placebo
controlled double-blind RCT evaluating the effectiveness of a 13-valent
conjugated pneumococcal vaccine in preventing vaccine-type pneumococcal CAP in
84,496 elderly in the Netherlands. Participants of CAPiTA, who consented and
provided information on health status (EQ-5D) and socio-demographic background at
the time of vaccination, constitute the source population of CHO-CAP and are
eligible for the nested matched cohort study. CHO-CAP patients hospitalized with
CAP form the "diseased" cohort and the "non-diseased" cohort consists of
unaffected persons (i.e. no CAP). Observations in the diseased cohort and in
matched controls from the non-diseased cohort are used to determine excess costs
and QoL changes attributable to CAP.Based on an estimated 2,000 CAPiTA
participants being hospitalized with CAP and an assumed CHO-CAP participation
rate of 30% of all CAPiTA participants (+/-25,000), 600 CAP episodes are expected
among CHO-CAP participants (the "diseased" cohort). For each patient with CAP,
two non-diseased CHO-CAP subjects will be selected from the CHO-CAP cohort, with
matching for age, gender and EQ-5D baseline-score. Data on healthcare and non
healthcare resources use, quality-of-life (using EQ-5D and SF-36 questionnaires)
and selected health outcomes will be collected at 0, 1, 6 and 12 months after
hospitalization for CAP.The CHO-CAP study was approved by the Central Committee
on Research involving Human Subjects in the Netherlands. DISCUSSION: With an
expected 600 CAP episodes this study will be one of the biggest prospectively
studied cohorts of hospitalized elderly with CAP with regard to resources use and
Qol data. Strengths of this study further include collection of out-of-pocket
costs of patients and productivity losses of both patients and their caregivers
and the follow-up period of up to one year post-discharge. This study is
therefore expected to add more in-depth knowledge on the short and longer term
outcomes of pneumonia in elderly. TRIAL REGISTRATION: ClinicalTrials.gov,
NCT00812084.
PMID- 24354589
TI - Contrasting host immuno-inflammatory responses to bacterial challenge within
venous and diabetic ulcers.
AB - Within chronic wounds, the relationship between the clinical diagnosis of
infection and bacterial/immuno-inflammatory responses is imprecise. This study
prospectively examined the interrelationship between clinical, microbiological,
and proinflammatory biomarker levels between chronic venous leg ulcers (CVLUs)
and diabetic foot ulcers (DFUs). Wound swabs and fluids were collected from CVLUs
(n = 18) and DFUs (n = 15) and diagnosed clinically as noninfected or infected;
and qualitative/quantitative microbiology was performed. CVLU and DFU fluids were
also analyzed for cytokine, growth factor, receptor, proteinase/proteinase
inhibitor; and oxidative stress biomarker (protein carbonyl, malondialdehyde, and
antioxidant capacity) levels. While no correlations existed between clinical
diagnosis, microbiology, or biomarker profiles, increasing bacterial bioburden
(>=10(7) colony-forming unit/mL) was associated with significant alterations in
cytokine, growth factor, and receptor levels. These responses contrasted between
ulcer type, with elevated and decreased cytokine, growth factor, and receptor
levels in CVLUs and DFUs with increasing bioburden, respectively. Despite
proteinase biomarkers exhibiting few differences between CVLUs and DFUs,
significant elevations in antioxidant capacities correlated with increased
bioburden in CVLU fluids, but not in DFUs. Furthermore, oxidative stress
biomarker levels were significantly elevated in all DFU fluids compared with
CVLUs. This study provides further insight into the contrasting disease-specific
host responses to bacterial challenge within infected CVLUs and DFUs.
PMID- 24354590
TI - Multiple traumatic neuromas after laser ablation treatment for viral warts.
PMID- 24354591
TI - The prevalence of syphilis at childbirth in Ireland: a six-year review.
AB - Re-emerging syphilis outbreaks across Europe have led to increasing syphilis
rates among women of child-bearing age. We, therefore, identified all forms of
syphilis cases among women hospitalized for delivery in Ireland over a six-year
period. Cases per annum ranged from 10 to 24 (13.8-32.9 per 100 000 maternities).
Rates of syphilis in this universally screened cohort were four times higher than
the general Irish population. Future studies examining the incidence of
congenital syphilis as well as patterns in follow-up treatment for the sero
positive mother and her infant are needed to better guide clinical intervention.
PMID- 24354592
TI - Characterization and thermal isomerization of (all-E)-lycopene.
AB - A large amount of (all-E)-lycopene was successfully purified from tomato paste
using an improved method that included a procedure to wash crystalline powder
with acetone. The total yield of the pure (all-E) form was at least 30%. The
melting point of (all-E)-lycopene was determined to be 176.35 degrees C by
differential scanning calorimetry (DSC) measurements. Bathochromic shifts were
observed in the absorption maxima of all solvents tested (at most a 36 nm shift
for lambda2 in carbon disulfide, as was observed in hexane) and were accompanied
by absorbance decreases, namely, a hypochromic effect, showing a higher
correlation between the position and the intensity of the main absorption bands.
This bathochromic shift was dependent upon the polarizability of the solvent
rather than its polarity. The structure of (all-E)-lycopene in CDCl3 and C6D6 was
identified on the basis of one- and two-dimensional nuclear magnetic resonance
(NMR) spectra, including (1)H and (13)C NMR, homonuclear correlation spectroscopy
((1)H-(1)H COSY), heteronuclear multiple-quantum coherence (HMQC), and
heteronuclear multiple-bond connectivity (HMBC). The rate constants of the
decrease in (all-E)-lycopene with hexane and benzene were calculated to be 3.19 *
10(-5) and 3.55 * 10(-5) s(-1), respectively. The equilibrium constants between
(all-E) and (13Z) isomers were estimated to be 0.29 in hexane and 0.31 in
benzene, respectively, from the point at which the amount of (13Z)-lycopene
reached its maximum.
PMID- 24354593
TI - Emerging protein kinase inhibitors for non-small cell lung cancer.
AB - INTRODUCTION: In the current paradigm of precision medicine in non-small cell
lung cancer (NSCLC), the therapeutic strategy is determined by the molecular
characteristics. The best examples of this approach are the kinase inhibitors
that selectively target tumors bearing an epidermal growth factor receptor (EGFR)
mutation or an anaplastic lymphoma kinase (ALK) rearrangement. Emerging protein
kinase inhibitors may enhance our ability to effectively treat these and other
genomic subtypes of NSCLC. AREAS COVERED: This article reviews the next
generation kinase inhibitors targeting EGFR and ALK-positive NSCLC. In addition,
targeted kinase inhibitors in clinical development for other specific molecular
subtypes of NSCLC are covered, including ROS1, BRAF, RET, HER2, KRAS (upstream of
the MEK kinase), MET, PIK3CA, FGFR1, DDR2, VEGFR and AAK. EXPERT OPINION: In EGFR
mutant NSCLC, there are several kinase inhibitors with promising activity, most
notably dacomitinib and CO-1686 in tumors with acquired resistance to EGFR
targeted therapy. Next-generation ALK inhibitors appear to have greater potency
than crizotinib and several ongoing trials may shed light on their role in both
ALK- and ROS1-positive NSCLC. While there is optimism regarding the role of
kinase inhibitors in other molecular subtypes, the available evidence is too
immature to make recommendations and results from prospective trials are needed.
PMID- 24354594
TI - Can too many copies spoil the broth?
AB - The success of Pichia pastoris as a heterologous expression system lies
predominantly in the impressive yields that can be achieved due to high
volumetric productivity. However, low specific productivity still inhibits the
potential success of this platform. Multi-(gene) copy clones are potentially a
quick and convenient method to increase recombinant protein titer, yet they are
not without their pitfalls. It has been more than twenty years since the first
reported use of multi-copy clones and it is still an active area of research to
find the fastest and most efficient method for generating these strains. It has
also become apparent that there is not always a linear correlation between copy
number and protein titer, leading to in-depth investigations into how to minimize
the negative impact of secretory stress and achieve clonal stability.
PMID- 24354595
TI - Experiences of preconception, pregnancy, and new motherhood for lesbian
nonbiological mothers.
AB - OBJECTIVE: To describe the experiences of preconception, pregnancy, and new
motherhood from the perspective of lesbian nonbiological mothers. DESIGN:
Descriptive phenomenology. SETTING: A private room at the study site and
participants' homes. PARTICIPANTS: Twenty-four self-identified lesbian
nonbiological mothers in a committed relationship and whose partner gave birth
within the past 2 years participated. All of the participants were from urban or
suburban areas in the Pacific Northwest. METHODS: Women participated in
semistructured in person interviews that were audio recorded and transcribed
verbatim for analysis. Coliazzi's method guided the process. RESULTS: An
overarching theme of "feeling different" permeated the experiences of
preconception, pregnancy, and new motherhood for the participants. The women's
narratives revealed seven themes that illustrated their experiences: (a)
Launching pregnancy: A roller coaster ride; (b) Having legal and biological
concerns: Biology prevails; (c) There is a little person in there: Dealing with
pregnancy issues; (d) Losing relationships over pregnancy: The elephant in the
room; (e) Feeling incomplete as a mother; (f) Carving a unique role: There are
very few of us out there; and (g) Sadness and regret: Nonbiological mothers get
the postpartum blues, too. CONCLUSIONS: The experience of preconception,
pregnancy, and new motherhood for nonbiological lesbian mothers is complicated by
the lack of biological and legal substantiation to the infant, few role models,
and limited social support. Nurses and health care providers cognizant of these
issues can play an important role in facilitating a positive transition to
motherhood for this population.
PMID- 24354596
TI - Fucoidan promotes early step of cardiac differentiation from human embryonic stem
cells and long-term maintenance of beating areas.
AB - Somatic stem cells require specific niches and three-dimensional scaffolds
provide ways to mimic this microenvironment. Here, we studied a scaffold based on
Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during
embryonic development, to support human embryonic stem cells (hESCs)
differentiation toward the cardiac lineage. A macroporous (pore 200 MUm) Fucoidan
scaffold was selected to support hESCs attachment and proliferation. Using a
protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and
transforming growth factor (TGFbeta) followed by tumor necrosis factor
(TNFalpha), an effector of cardiopoietic priming, we examined the cardiac
differentiation in the scaffold compared to culture dishes and embryoid bodies
(EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression
of the 3 genes encoding for transcription factors marking the early step of
embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01), and GATA4
(p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. The ability
of Fucoidan scaffolds to locally concentrate and slowly release TGFbeta and
TNFalpha was confirmed by Luminex technology. We also found that Fucoidan
scaffolds supported the late stage of embryonic cardiac differentiation marked by
a significantly higher atrial natriuretic factor (ANF) expression (p<0.001),
although only rare beating areas were observed. We postulated that absence of
mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed
by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological
staining of sarcomeric alpha-actinin. Nevertheless, Fucoidan scaffolds
contributed to the development of thin filaments connecting beating areas through
promotion of smooth muscle cells, thus enabling maintenance of beating areas for
up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising
biomaterial to control cardiac differentiation from hESCs that could be further
combined with mechanical stress to promote sarcomere formation at terminal stages
of differentiation.
PMID- 24354597
TI - Vitamin D levels and bone metabolism in Chinese adult patients with inflammatory
bowel disease.
AB - OBJECTIVE: We aimed to investigate the serum 25-hydroxyvitamin D3 (25[OH]D3 )
levels and bone metabolism in adult Chinese patients with inflammatory bowel
disease (IBD) and to evaluate the correlation between vitamin D levels and the
disease activity as well as the potential risk factors. METHODS: Age- and gender
matched cohort of IBD patients (124 with ulcerative colitis [UC] and 107 with
Crohn's disease [CD]) and 122 healthy controls were enrolled in this study. Serum
levels of 25(OH)D3 and bone mineral density (BMD) were measured, and the
correlation between the two parameters and the severity of the disease as well as
the clinical risk factors were analyzed. RESULTS: Serum 25(OH)D3 levels were
lower in UC (10.32 +/- 4.46 ng/mL, P < 0.001) and CD patients (11.57 +/- 5.02
ng/mL, P = 0.029) than that in healthy controls (12.87 +/- 4.40 ng/mL). 25(OH)D3
levels were negatively correlated with the disease severity of both UC (r =
0.371, P < 0.001) and CD (r = -0.285, P = 0.030). The incidences of osteopenia
and osteoporosis were high in the IBD patients (37.9% and 3.2% in UC and 30.8%
and 4.7% in CD, respectively). Cumulative quantity of glucocorticoids use was
significantly associated with osteopenia and osteoporosis in both UC (odds ratio
[OR] 1.219, 95% confidence interval [CI] 1.054-1.410, P = 0.008) and CD patients
(OR 1.288, 95% CI 1.033-1.606, P = 0.025). CONCLUSIONS: Vitamin D deficiency is
likely to occur in Chinese patients with IBD and is closely associated with the
severity of the disease. Glucocorticoids accumulation is a risk factor for
osteopenia and osteoporosis.
PMID- 24354598
TI - Osmolyte effects: impact on the aqueous solution around charged and neutral
spheres.
AB - We have performed atomistic molecular dynamics simulations to study the solvation
characteristics of model spheres for low concentrations of urea and
hydroxyectoine in aqueous solution. The spheres are either positively or
negatively charged with a valency of one or charge neutral. Our results
illustrate that the presence of osmolytes influences the solvation properties of
the spheres significantly. We have conducted a detailed investigation of water
properties like the mean dipolar relaxation times, water orientation parameters
around the spheres, dielectric constants, preferential binding behavior, water
self-diffusion coefficients, and free energies of solvation by thermodynamic
integration to study the influence of osmolytes in detail. Our findings indicate
that several factors like the charge of the spheres as well as the
characteristics of the osmolytes significantly influence the thermodynamic and
dynamic properties of the local water shell and the solvation process with regard
to varying enthalpic and entropic contributions.
PMID- 24354599
TI - Rapid ether and alcohol C-O bond hydrogenolysis catalyzed by tandem high-valent
metal triflate + supported Pd catalysts.
AB - The thermodynamically leveraged conversion of ethers and alcohols to saturated
hydrocarbons is achieved efficiently with low loadings of homogeneous M(OTf)n +
heterogeneous Pd tandem catalysts (M = transition metal; OTf = triflate; n = 4).
For example, Hf(OTf)4 mediates rapid endothermic ether ? alcohol and alcohol ?
alkene equilibria, while Pd/C catalyzes the subsequent, exothermic alkene
hydrogenation. The relative C-O cleavage rates scale as 3 degrees > 2 degrees >
1 degrees . The reaction scope extends to efficient conversion of biomass-derived
ethers, such as THF derivatives, to the corresponding alkanes.
PMID- 24354601
TI - Free-radical cascade alkylarylation of alkenes with simple alkanes: highly
efficient access to oxindoles via selective (sp3)C-H and (sp2)C-H bond
functionalization.
AB - A copper-catalyzed alkylarylation of alkenes with simple alkanes was achieved,
which not only provided an efficient method to prepare various alkyl-substituted
oxindoles, but also represented a novel strategy for selective sp(3) C-H
functionalization/C-C bond formation via a free-radical cascade process.
Additionally, selective activation of unactivated (sp(3))C-H and (sp(2))C-H bonds
by one single step is achieved in this system, which would also provide a novel
strategy for raising efficiency in C-H bond functionalization.
PMID- 24354600
TI - Theoretical study of the reaction formalhydrazone with singlet oxygen.
Fragmentation of the C=N bond, ene reaction and other processes.
AB - Photobiologic and synthetic versatility of hydrazones has not yet been
established with (1)O2 as a route to commonly encountered nitrosamines. Thus, to
determine whether the "parent" reaction of formalhydrazone and (1)O2 leads to
facile C=N bond cleavage and resulting nitrosamine formation, we have carried out
CCSD(T)//DFT calculations and analyzed the energetics of the oxidation pathways.
A [2 + 2] pathway occurs via diradicals and formation of 3-amino-1,2,3
dioxazetidine in a 16 kcal/mol(-1) process. Reversible addition or physical
quenching of (1)O2 occurs either on the formalhydrazone carbon for triplet
diradicals at 2-3 kcal mol(-1), or on the nitrogen (N(3)) atom forming
zwitterions at ~15 kcal/mol(-1), although the quenching channel by charge
transfer interaction was not computed. The computations also predict a facile
conversion of formalhydrazone and (1)O2 to hydroperoxymethyl diazene in a low
barrier 'ene' process, but no 2-amino-oxaziridine-O-oxide (perepoxide-like)
intermediate was found. A Benson-like analysis (group increment calculations) on
the closed-shell species are in accord with the quantum chemical results.
PMID- 24354603
TI - Introduction to the special issue: The spirituality of hope and healing: Seeking
the sacred in the midst of despair.
PMID- 24354604
TI - Hope in human attachment and spiritual connection.
AB - Using Karl Menninger's and Paul Pruyser's seminal writings, the author reviews
the tradition of thought about hope at The Menninger Clinic and discusses the
application of this tradition to patient education. From the perspective of
contemporary attachment theory and research, he expands on Paul Pruyser's view of
hope as based on an experience of benevolent connection. Such connection can be
found-and disrupted-in attachment to God and in spirituality more broadly. The
article concludes with commentary on the challenges clinicians face in making use
of religion and spirituality as a resource for fostering hope.
PMID- 24354605
TI - Spiritual awakening and depression in adolescents: a unified pathway or "two
sides of the same coin".
AB - Spiritual awakening is inherent to development in the second decade, as reflected
not only in millennia of religious faith traditions and indigenous culture but
also in recent genetic-twin and epidemiological studies. Developmentally
concomitant with spiritual awakening is the window of onset for the most
prevalent forms of adolescent suffering in post-industrial societies: depression
and related substance abuse and risk taking. Over the past fifteen years,
spirituality-a lived relationship with a Higher Power-has been found to be the
most robust protective factor against depression known to medical and social
sciences. The magnitude of the protective effect and its timing in adolescence
raises the question of a singular process or shared biological substrate
underlying spiritual awakening and onset of depression. Evidence for such a
shared physiology comes from a recent magnetic resonance imaging (MRI) study
suggesting that depression and spirituality in youth reveal "two sides of the
same coin."
PMID- 24354606
TI - Hope in caring for the deeply forgetful: enduring selfhood and being open to
surprises.
AB - Hope in the context of individuals with dementia and their carers is defined in
this paper in terms of an openness to surprises with regard to indicators of
continuing self-identity in the individual with dementia, active agency with
regard to carers and affected individuals to the extent possible, and the
affirmation of a theory of personhood and related moral status that breaks
through the limits and prejudices of hypercognitive values.
PMID- 24354607
TI - "Hope that is seen is no hope at all:" theological constructions of hope in
psychotherapy.
AB - Contemporary psychology and psychiatry have increasingly focused on hope as a
human phenomenon relevant to physical and psychological well-being. Contemporary
psychological research, however, often considers hope anthropocentrically and
cannot speak directly of the particular cultural, religious and theological
sustaining contexts of hope that, especially for persons of faith, give hope its
shape and meaning. In this paper I focus on three articulations of hope within
Jewish and Christian tradition-the Summa theologiae of Thomas Aquinas, the lament
psalms of the Hebrew Bible, and the post-Holocaust writing of Emil Fackenheim-to
argue that attention to these sustaining contexts is essential for understanding
what religious traditions mean by hope. Religious traditions display insights and
practices related to hope that both complement and challenge contemporary
psychological approaches to hope. Close attention to these determinative
traditions can therefore enrich and deepen the treatment of hope within
contemporary psychotherapeutic practice.
PMID- 24354608
TI - Conversations with Eeyore: spirituality and the generation of hope among mental
health providers.
AB - A growing body of research has highlighted the value of spiritual resources for
patients and their families. However, spirituality has been largely overlooked as
a source of hope and support for providers themselves. In this paper, the author
draws on theory, research, and practical examples to suggest that spirituality
could potentially assist providers struggling to generate and sustain their own
hope in work with clients who are in the midst of despair. The paper focuses on
three ways practitioners might access spiritual resources to facilitate hope in
their work: (1) by illuminating the sacred character of mental health work; (2)
by attending to the sacred dimension of clients' lives; and (3) by attending to
the experience of sacred moments in the healing relationship. These resources may
be of value not only to theistically-oriented practitioners but to nontheists as
well.
PMID- 24354612
TI - Evolution of the Thompson score during the first 6 h in infants with perinatal
asphyxia.
AB - AIM: This study aimed to determine the evolution of the Thompson score, which
provides composite grading of encephalopathy signs, during the first 6 h of birth
in neonates with perinatal asphyxia. METHODS: Twenty term infants with perinatal
asphyxia were prospectively studied from the University Hospital of Kinshasa
during a 12-month period. The Thompson score was performed after 1 h, then hourly
until 6 h of birth. RESULTS: Fourteen infants had a Thompson score >=7 and six
had a score <7 after 1 h of birth. The Thompson score remained higher than 7
after 3 h in nine infants (64.3%) and in four infants (25.6%) after 6 h. After 3
h of birth, four infants moved from a score >=7 to a score below 7. After 6 h,
five infants had a score below 7. Seventy per cent of patients had a Thompson
score higher than 7 after 1 h, 45% after 3 h and 20% after 6 h. CONCLUSION: The
Thompson score changes over the time during the first 6 h of birth, and this
should be taken into account when it is being used as an entry criterion for
cooling.
PMID- 24354613
TI - The polysiloxane cyclization equilibrium constant: a theoretical focus on small
and intermediate size rings.
AB - The nonlinear dependence of polysiloxane cyclization constants (log(K(x))) with
ring size (log(x)) is explained by a thermodynamic model that treats specific
torsional modes of the macromolecular chains with a classical coupled hindered
rotor model. Several parameters such as the dependence of the internal rotation
kinetic energy matrix with geometry, the effect of potential energy hindrance,
anharmonicity, and the couplings between internal rotors were investigated. This
behavior arises from the competing effects of local molecular entropy that is
mainly driven by the intrinsic transformation of vibrations in small cycles into
hindered rotations in larger cycles and configurational entropy.
PMID- 24354614
TI - Analysis of seven-membered lactones by computational NMR methods: proton NMR
chemical shift data are more discriminating than carbon.
AB - We report an NMR chemical shift study of conformationally challenging seven
membered lactones (1-11); computed and experimental data sets are compared. The
computations involved full conformational analysis of each lactone, Boltzmann
weighted averaging of the chemical shifts across all conformers, and linear
correction of the computed chemical shifts. DFT geometry optimizations [M06-2X/6
31+G(d,p)] and GIAO NMR chemical shift calculations [B3LYP/6-311+G(2d,p)]
provided the computed chemical shifts. The corrected mean absolute error (CMAE),
the average of the differences between the computed and experimental chemical
shifts for each of the 11 lactones, is encouragingly small (0.02-0.08 ppm for
(1)H or 0.8-2.2 ppm for (13)C). Three pairs of cis versus trans diastereomeric
lactones were used to assess the ability of the method to distinguish between
stereoisomers. The experimental shifts were compared with the computed shifts for
each of the two possible isomers. We introduce the use of a "match ratio"--the
ratio of the larger CMAE (worse fit) to the smaller CMAE (better fit). A greater
match ratio value indicates better distinguishing ability. The match ratios are
larger for proton data [2.4-4.0 (av = 3.2)] than for carbon [1.1-2.3 (av = 1.6)],
indicating that the former provide a better basis for discriminating these
diastereomers.
PMID- 24354615
TI - Characteristics of subjective recognition and computer-aided image analysis of
facial erythematous skin diseases: a cornerstone of automated diagnosis.
AB - BACKGROUND: Rosacea and seborrhoeic dermatitis are common diseases that cause
facial erythema. They have common features and are frequently misdiagnosed.
OBJECTIVES: To extract characteristic features of erythrotelangiectatic rosacea
(ETR), papulopustular rosacea (PPR) and seborrhoeic dermatitis (SEB) through
computer-aided image analysis (CAIA) and compare them with subjectively
recognized features and to use these findings to construct a decision tree for
differential diagnosis. METHODS: Thirty-four clinical photos of patients with
facial erythema were assessed: 12 patients were classified as showing ETR, 12 as
PPR and 10 as SEB. Five dermatologists blinded to the original diagnosis gave
their impressions of each photo. The mean, SD and T-zone to U-zone (T/U) ratios
of the erythema parameter a* (a* of the L*a*b* colour space) were calculated for
each photo using CAIA. These CAIA parameters were compared between impression
groups. The most closely related CAIA parameter for each disease was established
using the receiver-operating characteristic curve analysis. A decision tree which
predicts the diagnosis from given CAIA parameters was constructed. RESULTS: All
the photos classified as PPR generated impressions of PPR. However, approximately
30% of the photos classified as ETR generated impressions of SEB and vice versa.
PPR was characterized by a large SD of erythema of the cheek, ETR was
characterized by a large mean erythema of the U-zone, and SEB was characterized
by a large T/U ratio of mean erythema. Fifteen additional photos were examined:
the decision tree predicted the original diagnosis for 14, but incorrectly
predicted one case of ETR as SEB. CONCLUSIONS: The CAIA result of facial erythema
is well correlated with the actual clinical diagnosis. The accuracy of
differential diagnosis using a decision tree with CAIA parameters is as good as
that of global examination impressions of dermatologists.
PMID- 24354616
TI - Autologous platelet rich plasma: topical versus intradermal after fractional
ablative carbon dioxide laser treatment of atrophic acne scars.
AB - BACKGROUND: A proposal has recently been made regarding the potential adjuvant
use of platelet-rich plasma (PRP) with fractional carbon dioxide laser (FCL) for
the correction of acne scars. OBJECTIVE: To compare the efficacy and safety of
two administration modes of autologous PRP (intradermal injection (ID) and
topical application) after FCL with that of FCL alone in the treatment of
atrophic acne scars. PATIENTS AND METHODS: Thirty patients were randomly divided
into two groups. Both underwent split-face therapy. Group 1 was administered FCL
followed by ID PRP on one side and FCL followed by ID saline on the other. In
group 2, one cheek was treated with FCL followed by ID PRP, and the other
received FCL followed by topical PRP. Each patient received 3 monthly sessions.
The final assessment took place at 6 months. RESULTS: Combined PRP- and FCL
treated areas had a significantly better response (p = .03), fewer side effects,
and shorter downtime (p = .02) than FCL-treated areas, but there were no
significant differences in ID- and topical PRP-treated areas in degree of
response and downtime (p = .10); topically treated areas had significantly lower
pain scores. CONCLUSION: The current study introduces the combination of topical
PRP and FCL as an effective, safe modality in the treatment of atrophic acne
scars with shorter downtime than FCL alone and better tolerability than FCL
combined with ID PRP.
PMID- 24354617
TI - Zosteriform transient acantholytic dermatosis.
PMID- 24354619
TI - CCCTC-binding factor mediates effects of glucose on beta cell survival.
AB - OBJECTIVES: Pancreatic islet beta-cell survival is paramount for regulation of
insulin activity and for maintaining glucose homeostasis. Recently, Pax6 has been
shown to be essential for many vital functions in beta-cells, although many
molecular mechanisms of its homeostasis in beta-cells remain unclear. The present
study investigates novel effects of glucose- and insulin-induced CCCTC-binding
factor (CTCF) activity on Pax6 gene expression as well as for subsequent effects
of insulin-activated signalling pathways, on beta-cell proliferation. MATERIALS
AND METHODS: Pancreatic beta-TC-1-6 cells were cultured in DMEM and stimulated
with high concentrations of glucose (5-125 mm); cell viability was assessed by
MTT assay. Effects of CTCF on Pax6 were evaluated in the high glucose-induced
environment and CTCF/Erk-suppressed cells, by promoter reporter and western
blotting analyses. RESULTS: Increases in glucose and insulin concentrations
upregulated CTCF and consequently downregulated Pax6 in beta-cell survival and
proliferation. Knocking-down CTCF directly affected Pax6 transcription through
CTCF binding and blocked the response to glucose. Altered Erk activity mediated
effects of CTCF on controlling Pax6 expression, which partially regulated beta
cell proliferation. CONCLUSIONS: CTCF functioned as a molecular mediator between
insulin-induced upstream Erk signalling and Pax6 expression in these pancreatic
beta-cells. This pathway may contribute to regulation of beta-cell survival and
proliferation.
PMID- 24354620
TI - Gas6-induced tissue factor expression in endothelial cells is mediated through
caveolin-1-enriched microdomains.
AB - BACKGROUND: Gas6 has been shown to interact with Axl in endothelial cells and to
induce several signaling pathways involved in cell survival and proliferation.
However, the interaction of Gas6/Axl with lipid raft/caveolin-1 in endothelial
cells and its role in thrombosis are unknown. OBJECTIVES: We tested whether Axl
and/or caveolin-1 is involved in Gas6-induced Akt, ERK1/2, and c-Src activation
leading to altered tissue factor expression in endothelial cells. METHODS: Gas6
treated endothelial cells were transfected with small interfering RNA (siRNA) for
Axl, caveolin-1, c-Src, and Akt or treated with pharmacological inhibitors of c
Src and ERK1/2. Sucrose gradient centrifugation and confocal microscopy were used
to study lipid raft/caveolin-1-enriched fractions. Akt, ERK1/2, p38, and c-Src
activation was analyzed by Western blot analysis. Tissue factor expression was
assessed by real-time quantitative polymerase chain reaction and
immunofluorescence. RESULTS AND CONCLUSION: Gas6 induced Axl and c-Src
localization into lipid raft/caveolin-1-enriched fractions. Gas6 increased the
phosphorylation of Akt, ERK1/2, and c-Src but not p38. Using siRNA, we
demonstrated that Axl is required for Akt, ERK1/2, and c-Src activation after
Gas6 stimulation. siRNA for caveolin-1 blocked Gas6-induced phosphorylation of
Akt, ERK1/2, and c-Src. c-Src downregulation inhibited Gas6-induced Akt but not
ERK1/2 phosphorylation. Finally, Gas6 increased tissue factor mRNA and protein
expression in endothelial cells. Tissue factor expression was blocked by siRNA
for Axl, caveolin-1, or Akt as well as c-Src inhibition. These data demonstrate
that the signaling pathway Gas6/Axl/caveolin-1/c-Src/Akt is required for tissue
factor expression in endothelial cells, providing mechanistic insight into how
Gas6 exerts its prothrombotic role in the vasculature.
PMID- 24354621
TI - Detection of small hepatocellular carcinoma using gadoxetic acid-enhanced MRI: Is
the addition of diffusion-weighted MRI at 3.0T beneficial?
AB - OBJECTIVE: To determine whether adding diffusion-weighted imaging (DWI) to
gadoxetic acid-enhanced 3.0T magnetic resonance imaging (MRI) can improve the
detection of hepatocellular carcinoma (HCC), particularly for small lesions (<=2
cm) in patients with liver cirrhosis. METHODS: Data of patients diagnosed with
focal liver lesions who had undergone gadoxetic acid-enhanced 3.0T MRI and DWI
were retrospectively reviewed. Two radiologists (the observers) reviewed
independently MRI images in two reading sessions, that is, gadoxetic acid
enhanced images alone and the combination of DWI (b values: 0 and 600 s/mm(2) )
and gadoxetic acid-enhanced images. They assigned to each lesion a confidence
level based on a five-point scale. The area under the receiver operating
characteristic curve (AUROC), sensitivity and positive predictive value (PPV) for
the detection of HCC were calculated. RESULTS: Both observers found the AUROC of
the gadoxetic acid-enhanced images was slightly higher than that of the combined
DWI and gadoxetic acid-enhanced MRI images in the detection of HCC (observer 1:
0.947 +/- 0.030 vs 0.896 +/- 0.042, Z = 1.478, P = 0.139; observer 2: 0.917 +/-
0.038 vs 0.868 +/- 0.048, Z = 1.296, P = 0.195). The sensitivity for the
gadoxetic acid set alone was slightly higher than that for the combined set for
observer 1 (97% vs 84%) and slightly lower for observer 2 (74% vs 82%). The PPVs
were slightly higher for the gadoxetic acid set alone than for the combined set
for both observers (observer 1, 89% vs 80%; observer 2, 93% vs 78%); however,
none of the differences were statistically significant (P > 0.05). CONCLUSION:
There is no benefit in adding DWI to gadoxetic acid-enhanced MRI for the
detection of HCC at 3.0T.
PMID- 24354618
TI - Regulated proteolysis in bacterial development.
AB - Bacteria use proteases to control three types of events temporally and spatially
during the processes of morphological development. These events are the
destruction of regulatory proteins, activation of regulatory proteins, and
production of signals. While some of these events are entirely cytoplasmic,
others involve intramembrane proteolysis of a substrate, transmembrane signaling,
or secretion. In some cases, multiple proteolytic events are organized into
pathways, for example turnover of a regulatory protein activates a protease that
generates a signal. We review well-studied and emerging examples and identify
recurring themes and important questions for future research. We focus primarily
on paradigms learned from studies of model organisms, but we note connections to
regulated proteolytic events that govern bacterial adaptation, biofilm formation
and disassembly, and pathogenesis.
PMID- 24354622
TI - Single incision laparoscopic right colectomy: a systematic review and meta
analysis.
AB - AIM: A meta-analysis was performed to compare the outcome of single incision
laparoscopic right hemicolectomy with standard multiport laparoscopic right
hemicolectomy. METHOD: A systematic search of databases was carried out to
extract comparative studies (randomized and non-randomized, prospective and
retrospective). Data were analysed according to Cochrane Collaboration
guidelines. A meta-analysis was performed when the data permitted this form of
analysis. RESULTS: Nine comparative studies were retrieved comprising 241
patients with single incision and standard laparoscopy. None of these was
randomized. There was no significant difference between the two methods for the
primary end-points of mortality, morbidity and cancer-specific parameters and for
the secondary end-points of operation time, blood loss, ileus, hospital stay and
conversion. It was not possible to analyse pain and cosmetics data owing to
insufficient information. CONCLUSION: Single incision laparoscopic right
hemicolectomy is comparable with standard multiport laparoscopic right
hemicolectomy in primary and secondary outcomes. Given current information it is
justified to use single incision laparoscopic right hemicolectomy, but there is a
need for a prospective randomized study.
PMID- 24354624
TI - Accurate determination of genetic identity for a single cacao bean, using
molecular markers with a nanofluidic system, ensures cocoa authentication.
AB - Cacao (Theobroma cacao L.), the source of cocoa, is an economically important
tropical crop. One problem with the premium cacao market is contamination with
off-types adulterating raw premium material. Accurate determination of the
genetic identity of single cacao beans is essential for ensuring cocoa
authentication. Using nanofluidic single nucleotide polymorphism (SNP) genotyping
with 48 SNP markers, we generated SNP fingerprints for small quantities of DNA
extracted from the seed coat of single cacao beans. On the basis of the SNP
profiles, we identified an assumed adulterant variety, which was unambiguously
distinguished from the authentic beans by multilocus matching. Assignment tests
based on both Bayesian clustering analysis and allele frequency clearly separated
all 30 authentic samples from the non-authentic samples. Distance-based principle
coordinate analysis further supported these results. The nanofluidic SNP
protocol, together with forensic statistical tools, is sufficiently robust to
establish authentication and to verify gourmet cacao varieties. This method shows
significant potential for practical application.
PMID- 24354625
TI - Are female fetuses more reactive when mother eats chocolate?
PMID- 24354623
TI - Cell cycle alterations induced by urban PM2.5 in bronchial epithelial cells:
characterization of the process and possible mechanisms involved.
AB - BACKGROUND: This study explores and characterizes cell cycle alterations induced
by urban PM2.5 in the human epithelial cell line BEAS-2B, and elucidates possible
mechanisms involved. METHODS: The cells were exposed to a low dose (7.5
MUg/cm(2)) of Milan winter PM2.5 for different time points, and the cell cycle
progression was analyzed by fluorescent microscopy and flow cytometry. Activation
of proteins involved in cell cycle control was investigated by Western blotting
and DNA damage by (32)P-postlabelling, immunostaining and comet assay. The
formation of reactive oxygen species (ROS) was quantified by flow cytometry. The
role of PM organic fraction versus washed PM on the cell cycle alterations was
also examined. Finally, the molecular pathways activated were further examined
using specific inhibitors. RESULTS: Winter PM2.5 induced marked cell cycle
alteration already after 3 h of exposure, represented by an increased number of
cells (transient arrest) in G2. This effect was associated with an increased
phosphorylation of Chk2, while no changes in p53 phosphorylation were observed at
this time point. The increase in G2 was followed by a transient arrest in the
metaphase/anaphase transition point (10 h), which was associated with the
presence of severe mitotic spindle aberrations. The metaphase/anaphase delay was
apparently followed by mitotic slippage at 24 h, resulting in an increased number
of tetraploid G1 cells and cells with micronuclei (MN), and by apoptosis at 40 h.
Winter PM2.5 increased the level of ROS at 2 h and DNA damage (8-oxodG, single-
and double stand breaks) was detected after 3 h of exposure. The PM organic
fraction caused a similar G2/M arrest and augmented ROS formation, while washed
PM had no such effects. DNA adducts were detected after 24 h. Both PM-induced DNA
damage and G2 arrest were inhibited by the addition of antioxidants and alpha
naphthoflavone, suggesting the involvement of ROS and reactive electrophilic
metabolites formed via a P450-dependent reaction. CONCLUSIONS: Milan winter PM2.5
rapidly induces severe cell cycle alterations, resulting in increased frequency
of cells with double nuclei and MN. This effect is related to the metabolic
activation of PM2.5 organic chemicals, which cause damages to DNA and spindle
apparatus.
PMID- 24354626
TI - Anatomic analysis specific for the endoscopic approach to the inferior, medial
and lateral orbit.
AB - INTRODUCTION: The endoscopic approaches to the medial and inferior orbital walls
have continued to grow in popularity. The ability to provide a safe approach to
the orbit through this technique has been described in a handful of studies. Even
though metric analyses have been conducted on orbital anatomy, few have outlined
the anatomical relations pertinent to endoscopic surgery. The goal is to provide
improved understanding of the complex anatomy encountered through anatomical
dissections and metric analysis of the orbit. This information could assist in
approach selection during preoperative planning. METHODS: Anatomical dissections
via transantral and endonasal approaches were used to define the limits with
current endoscopic sinus surgery instrumentation. The surface area was then
calculated of the floor and medial wall to assess access created by the
approaches. The path of the infraorbital canal was conducted to assess its
placement within the orbital floor. RESULTS: The transantral and endonasal
approaches to the orbit provided an adequate surgical window inferiorly and
medially. This was confirmed by the surface area calculations. Access laterally
was also possible, however, it became limited as dissection advanced superior to
the lateral rectus muscle. The infraorbital canal was located consistently at
midline on the orbital floor. CONCLUSION: Endoscopic access to the medial and
inferior parts of the orbit is feasible and creates adequate access with current
instrumentation. Knowing the surgical boundaries and the amount of exposure
created can assist the surgeon in deciding a minimally invasive approach.
PMID- 24354628
TI - Neuropathologic analysis of hematomas evacuated from patients with spontaneous
intracerebral hemorrhage.
AB - Spontaneous intracerebral hemorrhage (ICH) is a devastating cause of morbidity
and mortality. Intraparenchymal hematomas are often surgically evacuated. This
generates fragments of perihematoma brain tissue that may elucidate their
etiology. The goal of this study is to analyze the value of these specimens in
providing a possible etiology for spontaneous ICH as well as the utility of using
immunohistochemical markers to identify amyloid angiopathy. Surgically resected
hematomas from 20 individuals with spontaneous ICH were examined with light
microscopy. Hemorrhage locations included 11 lobar and nine basal ganglia
hemorrhages. Abeta immunohistochemistry and Congo red stains were used to confirm
the presence of amyloid angiopathy, when this was suspected. Evidence of cerebral
amyloid angiopathy (CAA) was observed in eight of the 20 specimens, each of which
came from lobar locations. Immunohistochemistry confirmed CAA in the brain
fragments from these eight individuals. Patients with immunohistochemically
confirmed CAA were older than patients without CAA, and more likely to have lobar
hemorrhages (OR 3.0 and 3.7, respectively). Evidence of CAA was not found in any
of the basal ganglia specimens. One specimen showed evidence of CAA-associated
angiitis, with formation of a microaneurysm in an inflamed segment of a CAA
affected arteriole, surrounded by acute hemorrhage. In another specimen, Abeta
immunohistochemistry showed the presence of senile plaques suggesting concomitant
Alzheimer's disease (AD) changes. Surgically evacuated hematomas from patients
with spontaneous ICH should be carefully examined, paying special attention to
any fragments of included brain parenchyma. These fragments can provide evidence
of the etiology of the hemorrhage. Markers such as Abeta 1-40 can help to
identify underlying CAA, and should be utilized when microangiopathy is
suspected. Given the association of (Abeta) CAA with AD, careful examination of
entrapped brain fragments may also provide evidence of AD in a given patient.
PMID- 24354627
TI - Monitoring the efficacy and safety of three artemisinin based-combinations
therapies in Senegal: results from two years surveillance.
AB - BACKGROUND: Malaria remains a major public health problem in developing
countries. Then in these countries prompt access to effective antimalarial
treatment such as Artemisinin based-Combination Therapies (ACT) proves to be an
essential tool for controlling the disease. In Senegal, since 2006 a nationwide
scaling up program of ACT is being implemented. In this context it has become
relevant to monitor ACT efficacy and provide recommendations for the Senegalese
national malaria control program. METHODS: An open randomized trial was conducted
during two malaria transmission seasons (2011 and 2012) to assess the efficacy
and safety of three combinations: dihydro-artemisinin-piperaquine (DHAPQ),
artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ). The primary end
point of the study was represented by a PCR adjusted adequate clinical and
parasitological response (ACPR) at day 28. Secondary end points included: (i) a
ACPR at days 35 and 42, (ii) a parasite and fever clearance time, (iii) ACTs
safety and tolerability. The 2003 WHO's protocol for antimalarial drug evaluation
was used to assess each outcome. RESULTS: Overall, 534 patients were randomized
selected to receive, either ASAQ (n = 180), AL (n = 178) or DHAPQ (n = 176). The
PCR adjusted ACPR at day 28 was 99.41% for the group ASAQ, while that was 100% in
the AL and DHAPQ groups (p = 0.37). The therapeutic efficacy was evaluated at
99.37% in the ASAQ arm versus 100% in AL and DHAPQ arm at day 35 (p = 0.37). At
day 42, the ACPR was 99.27% in the ASAQ group versus 100% for both AL and DHAPQ
groups, (p = 0.36). No serious adverse event was noted during the study period.
Also a similar safety profile was noted in the 3 study groups. CONCLUSION: In the
context of scaling up of ACTs in Senegal, ASAQ, AL and DHAPQ are highly effective
and safe antimalarial drugs. However, it's remains important to continue to
monitor their efficacy. TRIAL REGISTRATION: PACTR 201305000552290.
PMID- 24354629
TI - Hooking up and risk behaviors among first semester college men: what is the role
of precollege experience?
AB - Some scholars assert that a hookup culture exists on college campuses and that
individuals who attend college are socialized into a hookup script. This study
examines hooking up among first-semester college men (N = 158), with specific
attention to precollege heavy episodic drinking (i.e., binge drinking) and
precollege hookup experience. We found that freshman men begin a pattern of
hooking up well before attending college. After controlling for known correlates
of hooking up, men had more hookup partners during their first semester at
college if they engaged in greater levels of precollege binge drinking and had
greater precollege hookup experience. Men were also more likely to have
penetrative sex hookups (i.e., oral sex and/or intercourse) if they had done so
prior to college. Precollege binge drinking and precollege hookup experience were
also associated with unplanned sexual activity when drinking, and men were more
likely to have unprotected sex when drinking during their first semester if they
engaged in more frequent precollege binge drinking. Implications for intervention
and future research are discussed.
PMID- 24354630
TI - A novel use of near-infrared fluorescence imaging during robotic surgery without
contrast agents.
AB - We describe a novel use of near-infrared fluorescence (NIRF) imaging without
contrast agents, like indocyanine green, to identify otherwise obscured
intraluminal areas of interest during robot-assisted laparoscopic (RAL) surgery
marked by the white light (WL) of endoscopic instruments. By filtering light
wavelengths below near-infrared, NIRF imaging causes the WL of the endoscopes to
illuminate green while allowing simultaneous vision of the surrounding tissues.
With this visualization, intraoperative ureteroscopy was used to identify the
extent of a ureteral stricture in a patient undergoing RAL partial ureterectomy.
Cystoscopy was used to identify bladder diverticula and tumor locations in three
patients undergoing RAL partial cystectomy with or without diverticulectomy and
the ureteral orifice in another patient undergoing RAL nephroureterectomy. This
technique enabled more precise identification of important areas and successful
completion of RAL surgery in these five patients, which serves as proof of
concept for broader applications in RAL surgery.
PMID- 24354631
TI - 'Sometimes it feels as if the world goes on without me': adolescents' experiences
of living with chronic fatigue syndrome.
AB - AIMS AND OBJECTIVES: To explore the experience of being an adolescent with
chronic fatigue syndrome. BACKGROUND: Despite ample research, chronic fatigue
syndrome is still poorly understood, and there are still controversies related to
the illness. Adolescents with chronic fatigue syndrome are often unable to attend
school and lose social relations with friends. The challenges they face will
affect their quality of life. DESIGN: A qualitative, phenomenological
hermeneutical design. METHOD: Six boys and twelve girls, aged 12-18, were
interviewed, emphasising their own experiences living with chronic fatigue
syndrome. Analyses were performed using a phenomenological hermeneutical method.
RESULTS: The core theme, 'Sometimes it feels as if the world goes on without me',
encompasses the feelings an adolescent living with chronic fatigue syndrome might
have about life. The core theme was supported by four subthemes: 'On the side of
life--locked in and shut out'; 'the body, the illness and me'; 'if the illness is
not visible to others, does it exist?'; and 'handling life while hoping for a
better future'. The subthemes reflect the experience of social isolation, their
own and others' understanding of the illness and hope for the future.
CONCLUSIONS: Not being able to be with friends, or attend school, made the
adolescents feel different and forgotten. They felt alienated in their own bodies
and were struggling to be visible to themselves and to their surroundings.
Spending less time with friends and more time with their parents constituted a
threat to independence and development. Yet they managed to envision a better
future despite all the difficulties. RELEVANCE FOR CLINICAL PRACTICE: To provide
effective support and constructive relations to adolescents with chronic fatigue
syndrome, all health professions involved need insight from the persons who are
themselves ill. Health centres could function as resource centres for patients
and healthcare professionals.
PMID- 24354632
TI - Epidermal dynamics and patterns of intraepidermal melanoma.
AB - BACKGROUND: Dermatopathologists know that the epidermis represents a dynamic
compartment and that its cells mature from the basal layer to the skin surface in
approximately 45 days. What may seem intuitive - but not obvious - is that the
dynamics of the epidermis can affect the patterns of melanoma cells within the
epidermis. Here this conjecture is explored with an abstract, theoretical model.
METHODS: To control the independent effects of epidermal replacement velocity and
thickness as well as rate of melanoma cell penetration of the epidermis, an
abstraction of the epidermis was created and simulated via computer. RESULTS:
Simulated plots of the epidermis show that the number and pattern of melanoma
cells in the epidermis is affected by the probability of melanoma cells entering
the epidermis, by the velocity of epidermal replacement and by epidermal
thickness. CONCLUSION: This analysis suggests that the dynamics of the epidermis
are sufficient to affect the patterns of melanoma cells within the epidermis.
PMID- 24354633
TI - Subtle changes in surface chemistry affect embryoid body cell differentiation:
lessons learnt from surface-bound amine density gradients.
AB - Advanced approaches to direct the differentiation of embryonic stem cells are
highly sought after. The surface-bound chemical gradient format is a powerful
screening approach that can be deployed to study changes in stem cell behavior as
a function of subtle changes in surface chemistry. Here, we investigate the
spontaneous differentiation of cells derived from differentiating mouse embryoid
body (mEB) cells into endoderm, mesoderm, and ectoderm following culture on
surface-bound gradients of chemical functional groups in the absence of
differentiation-biasing bioactive factors. Gradients were created using a
diffusion-controlled plasma polymerization technique. The generated coating
ranged from hydrophobic 1,7-octadiene (OD) plasma polymer at one end of the
gradient to a more hydrophilic allylamine (AA) plasma polymer on the opposite
end. The gradient surface was divided into seven equal regions of progressively
increasing AA plasma polymer content and mEB cell response within these regions
was compared. Cells adhered preferentially to the central regions of the
gradient; however, cell proliferation increased toward AA-plasma-polymer-rich end
of the gradient. Variation in the expression of germ layer markers was noted
across the gradient surface. High AA:OD plasma polymer ratios triggered cell
differentiation toward both mesoderm and ectoderm. Expression of tissue-specific
markers, in particular, KRT18, AFP, and TNNT2, was strikingly responsive to
subtle changes in surface chemistry, exhibiting vastly different expression
levels between adjacent regions. Our results suggest that the surface-bound
gradient platform is well suited to screening surface chemistries for use in the
field of stem cell technologies and regenerative medicine.
PMID- 24354634
TI - N-alkoxyheterocycles as irreversible photooxidants.
AB - Irreversible photooxidation based on N-O bond fragmentation is demonstrated for N
methoxyheterocycles in both the singlet and triplet excited state manifolds. The
energetic requirements for bond fragmentation are studied in detail. Bond
fragmentation in the excited singlet manifold is possible for pipi* singlet
states with energies significantly larger than the N-O bond dissociation energy
of ca 55 kcal mol(-1). For the npi* triplet states, N-O bond fragmentation does
not occur in the excited state for orbital overlap and energetic reasons.
Irreversible photooxidation occurs in the singlet states by bond fragmentation
followed by electron transfer. Irreversible photooxidation occurs in the triplet
states via bimolecular electron transfer to the donor followed by bond
fragmentation. Using these two sensitization schemes, donors can be irreversibly
oxidized with oxidation potentials ranging from ca 1.6-2.2 V vs SCE. The
corresponding N-ethylheterocycles are characterized as conventional reversible
photooxidants in their triplet states. The utility of these sensitizers is
demonstrated by irreversibly generating the guanosine radical cation in buffered
aqueous solution.
PMID- 24354635
TI - Polycationic adamantane-based dendrons of different generations display high
cellular uptake without triggering cytotoxicity.
AB - Dendrons used as synthetic carriers are promising nanostructures for biomedical
applications. Some polycationic dendritic systems, such as the commercially
available polyethylenimine (PEI), have the ability to deliver genetic material
into cells. Nevertheless, polycationic vectors are often associated with
potential cellular toxicity, which prevents their use in clinical development. In
this context, our research focused on the design and synthesis of a novel type of
polycationic dendrons that are able to penetrate into cells without triggering
cytotoxic effects. We synthesized first- and second-generation polycationic
adamantane-based dendrons via a combined protection/deprotection strategy
starting from different adamantane scaffolds. The linker between the adamantane
cores is constituted of short ethylene glycol chains, and the periphery consists
of ammonium and guanidinium groups. None of these dendritic structures, which we
previously called HYDRAmers, displayed significant cytotoxicity effects on two
different cell lines (RAW 264.7 and HeLa). Conjugation of the fluorescent probe
cyanine 5 at their focal point via click chemistry permitted the evaluation of
their cellular internalization. All of the dendrons penetrated through the
membrane with efficient cellular uptake depending of the dendron generation and
the nature of the peripheral groups. These results suggest that the polycationic
HYDRAmers are potentially interesting as new vectors in biomedical applications,
including gene and drug delivery.
PMID- 24354637
TI - Repair of a large defect of the upper lip.
PMID- 24354638
TI - Versatile oxidative approach to carbazoles and related compounds using MoCl5.
AB - The unique oxidizing power of molybdenum pentachloride provides an easy to
perform, versatile, and high yielding method to construct carbazoles and the
corresponding dibenzo analogues of thiophene, furan, and selenophene. The
coupling reaction tolerates a variety of functional groups. The synthesis is
highly modular. By this approach a precursor for the naturally occurring
carbazole koenigicine was prepared.
PMID- 24354639
TI - Copper/silver-mediated cascade reactions for the construction of 2
sulfonylbenzo[b]furans from trans-2-hydroxycinnamic acids and sodium sulfinates.
AB - Efficient construction of 2-sulfonylbenzo[b]furans is achieved from readily
available trans-2-hydroxycinnamic acids and sodium sulfinates mediated by the
CuCl2.2H2O/AgTFA system under mild conditions. This unprecedented synthetic
protocol provides expedient access to a series of products in one step via a
protodecarboxylation/C-S bond formation/C-O bond formation cascade.
PMID- 24354641
TI - Myxofibrosarcoma arising in a burn scar.
PMID- 24354640
TI - Selection for chloroquine-sensitive Plasmodium falciparum by wild Anopheles
arabiensis in Southern Zambia.
AB - BACKGROUND: The emergence of parasite drug resistance, especially Plasmodium
falciparum, persists as a major obstacle for malaria control and elimination. To
develop effective public health containment strategies, a clear understanding of
factors that govern the emergence and spread of resistant parasites in the field
is important. The current study documents selection for chloroquine-sensitive
malaria parasites by wild Anopheles arabiensis in southern Zambia. METHODS: In a
2,000-sq km region, mosquitoes were collected from human sleeping rooms using
pyrethrum spray catches during the 2006 malaria transmission season. After
morphological examination and molecular confirmation, vector mosquitoes were
dissected to separate head and thorax from the abdominal section, followed by PCR
screening for P. falciparum infection. Human residents of all ages were tested
for P. falciparum parasitaemia by microscopy and PCR. Plasmodium falciparum
infections were genotyped at the chloroquine resistance-conferring amino acid
codon 76 of the PfCRT gene, using PCR and restriction enzyme digestion. RESULTS:
In the human population there was nearly 90% prevalence of the chloroquine
resistant PfCRT K76T mutant, with no significant differences in polymorphism
among smear-positive and smear-negative (submicroscopic) infections (p = 0.323, n
= 128). However, infections in both abdominal and salivary gland phases of the
An. arabiensis vector exhibited wild type K76-bearing parasites with up to 9X
higher odds (OR (95% CI): 9 (3.7-20.2), p < 0.0005, n = 125), despite having been
acquired from humans within a few weeks. CONCLUSIONS: Anopheles arabiensis
selects for wild-type K76-bearing P. falciparum during both abdominal and
salivary gland phases of parasite development. The rapid vectorial selection,
also recently seen with antifolate resistance, is evidence for parasite fitness
cost in the mosquito, and may underpin regional heterogeneity in the emergence,
spread and waning of drug resistance. Understanding the nature and direction of
vector selection could be instrumental for rational curtailment of the spread of
drug resistance in integrated malaria control and elimination programmes.
PMID- 24354642
TI - Factors affecting adherence to short-course ARV prophylaxis for preventing mother
to-child transmission of HIV in sub-Saharan Africa: a review and lessons for
future elimination.
AB - Despite the biomedical potential to eliminate vertical HIV transmission, drug
adherence to short regimens is often sub-optimal. To inform future programmes, we
reviewed evidence on the factors influencing maternal and infant drug adherence
to preventing MTCT drug regimens at delivery in sub-Saharan Africa. A literature
review yielding 14 studies on adherence to drug regimes among HIV-positive
pregnant women and mothers in sub-Saharan Africa was conducted. Rates of maternal
adherence to preventive drug regimens at time of delivery varied widely across
sites between 35 and 93.5%. Factors most commonly associated with low adherence
to antiretroviral therapy (ARV) prophylaxis for preventing MTCT at the health
system level include giving birth at home, quality and timing of HIV testing and
counselling, and late distribution of nevirapine (NVP). Socio-demographic and
demand-side factors include fear of stigma, lack of male involvement, fear of
partner's reaction to disclosure, few antenatal (ANC) visits, young age and lack
of education. With the implementation of the newly published WHO guidelines
recommending triple-drug ARV regimen during pregnancy and breastfeeding for all
women with HIV, it is important that women are able to adhere to recommended drug
regimens. Service improvements should include clear and timely communication with
women about the benefits of combined regimens and greater emphasis on patient
confidentiality. Efforts must be made to help women overcome barriers that reduce
adherence, such as financial logistical challenges, social stigma and women's
fear of violence.
PMID- 24354643
TI - Biamphiphilic ionic liquid induced folding alterations in the structure of bovine
serum albumin in aqueous medium.
AB - 3-Methyl-1-octylimidazolium dodecylsulfate, [C8mim][C12OSO3], a vesicle forming
biamphiphilic ionic liquid (BAIL) (J. Phys. Chem. B 2012, 116, 14363-14374), has
been found to induce significant folding alterations in the structure of bovine
serum albumin (BSA) in the aqueous medium at pH 7.0. Such alterations have been
investigated in detail using various physicochemical and spectroscopic
techniques. Different concentration regimes (monomeric, shared aggregation, and
post-vesicular) of [C8mim][C12OSO3]-BSA interactions have been defined through
adsorption and binding isotherms using tensiometry and isothermal titration
calorimetry (ITC). Fluorimetry, circular dichroism (CD), and dynamic light
scattering (DLS) measurements have shown that [C8mim][C12OSO3] induces a small
unfolding of BSA in the monomeric regime at low concentration (designated as
C(f)), which is followed by a refolding up to critical aggregation concentration
(CAC) (designated as C1). Above C1, i.e., in the shared aggregation concentration
regime, again a small unfolding of BSA was observed up to critical vesicular
concentration (CVC) (designated as C2). In the vesicular and post-vesicular
regimes, the BSA remained stable against folding alterations. The kinetic
stability of BSA in the vesicular concentration regimes was studied for a month
using turbidimetry. It has been found that [C8mim][C12OSO3] stabilizes BSA
against the aggregation which is the major cause of protein destabilization. The
present study gives insights for the design of surface active ILs for protein
stabilization as a potential replacement for the mixed micelles of conventional
surfactants used in detergent industries for enzyme stabilization and as an
artificial chaperone.
PMID- 24354644
TI - Lack of secondary microthrombosis after thrombin-induced stroke in mice and non
human primates.
AB - BACKGROUND: Secondary microthrombosis is a major pathophysiologic mechanism
leading to brain damage following transient mechanical vascular occlusion (TMVO),
the most widely used experimental stroke model. Whether secondary microthrombosis
also occurs in non-TMVO stroke models represents an important issue for clinical
translation of antimicrothrombosis therapeutic strategies. OBJECTIVES: To assess
the occurrence and the pathogenic role of secondary microthrombosis in two
thrombin-induced stroke models in mice and non-human primates (Macaca mulatta).
METHODS: Stroke was induced in mice and non-human primates by intra-arterial
administration of recombinant thrombin. This method induces the formation of a
fibrin-rich thrombus, which is spontaneously dissolved in the following hours by
the endogenous fibrinolytic system. Perfusion-weighted imaging and fluorescent
lectin microangiography were performed after recanalization to detect secondary
microthrombosis. Moreover, to investigate its pathogenic role, thrombin-induced
stroke was induced in bradykinin receptor B1 (B1R) knockout mice, which are
protected from the thromboinflammation responsible for secondary microthrombosis
in TMVO models. RESULTS: Reperfusion was stable and complete in all mice and non
human primates tested, revealing no secondary decrease in cerebral blood flow. No
evidence of secondary microthrombosis was found in the two models. Accordingly,
deficiency in B1R did not protect the mice from brain damage after thrombin
induced stroke. CONCLUSIONS: Our data demonstrate that secondary microthrombosis
does not occur after thrombin-induced stroke. In view of this, the
pathophysiologic roles of hematologic players promoting or protecting against
secondary microthrombosis (such as factor XII, von Willebrand factor, and T
cells) deserve to be re-evaluated in non-TMVO stroke models.
PMID- 24354645
TI - Cell polarization in budding and fission yeasts.
AB - Polarization is a fundamental cellular property, which is essential for the
function of numerous cell types. Over the past three to four decades, research
using the best-established yeast systems in cell biological research,
Saccharomyces cerevisiae (or budding yeast) and Schizosaccharomyces pombe (or
fission yeast), has brought to light fundamental principles governing the
establishment and maintenance of a polarized, asymmetric state. These two
organisms, though both ascomycetes, are evolutionarily very distant and exhibit
distinct shapes and modes of growth. In this review, we compare and contrast the
two systems. We first highlight common cell polarization pathways, detailing the
contribution of Rho GTPases, the cytoskeleton, membrane trafficking, lipids, and
protein scaffolds. We then contrast the major differences between the two
organisms, describing their distinct strategies in growth site selection and
growth zone dimensions and compartmentalization, which may be the basis for their
distinct shapes.
PMID- 24354646
TI - Epidermal hydration levels in patients with rosacea improve after minocycline
therapy.
AB - BACKGROUND: Patients with rosacea frequently report increased skin sensitivity,
with features suggestive of an abnormal stratum corneum (SC) permeability
barrier. Sebum, pH and hydration levels influence epidermal homeostasis. The
correlation of changes in these parameters with clinically effective treatment
has not been previously analysed. OBJECTIVES: To analyse sebum, pH and epidermal
hydration levels of patients with papulopustular rosacea (PPR) before and after
treatment with systemic minocycline. METHODS: We analysed sebum casual levels, pH
and hydration along with erythema levels (as a marker of disease activity and
response to treatment) on seven designated facial sites of 35 patients with
active PPR and compared the results with values on the same sites of 34 control
subjects with normal facial skin. To determine the effect of minocycline on these
parameters, we re-examined the patients with PPR at the same sites after a 6-week
course of treatment. RESULTS: Patients with untreated PPR had significantly
increased erythema indices, normal sebum casual levels, a more alkaline
centrofacial region and reduced epidermal hydration levels compared with
controls. Treatment with minocycline resulted in reduced erythema and increased
hydration levels, with the most marked changes evident in the cheeks (13.3%
reduction in erythema indices, P < 0.001; 12.4% increase in hydration levels, P =
0.012). There was no change in skin pH or sebum casual levels following
treatment. CONCLUSION: Patients with PPR have increased erythema indices, normal
sebum casual levels, a more alkaline centrofacial region and reduced epidermal
hydration levels compared with control subjects. Treatment with systemic
minocycline reduces erythema and increases hydration, in the absence of any
change in skin pH or sebum casual levels.
PMID- 24354647
TI - Subjective quality of life in At-Risk Mental State for psychosis patients:
relationship with symptom severity and functional impairment.
AB - AIMS: The understanding of factors related to poor subjective quality of life
(sQoL) in early psychosis patients is important for both research and treatment
efforts. This study examined how sQoL is associated with age at onset of
prodromal symptoms, duration of untreated illness (DUI), symptom severity,
premorbid functioning and current functional impairment in At-Risk Mental State
(ARMS) for psychosis patients. METHODS: Forty ARMS patients were assessed for
sQoL, symptom severity, premorbid functioning, and social and role functioning.
RESULTS: As expected, a large number of significant and negative correlations
between sQoL domains and several symptom dimensions emerged, especially for
negative symptoms, behavioural change and depression. Poor premorbid functioning
in late adolescence was associated with impairments in the psychological health
and social relationship domains of sQoL. Current functional impairment was
associated with all sQoL domains. Neither age at onset of prodromal symptoms nor
DUI was related with sQoL. CONCLUSIONS: Findings indicate that different domains
of sQoL are differentially and meaningfully associated with symptom severity and
functional impairment, suggesting that greater symptom severity and poor
functioning are already related with decreased sQoL in the ARMS for psychosis
stage. Furthermore, findings highlight the importance of examining functional
impairment and affective-motivational symptoms in future research on sQoL in ARMS
populations due to their strong relationship with poor sQoL. Finally, findings
underscore the importance of addressing the social and occupational dysfunctions
already present in early psychosis with psychosocial interventions.
PMID- 24354648
TI - Advances in Ecological Speciation: an integrative approach.
AB - The role of natural selection in promoting reproductive isolation has received
substantial renewed interest within the last two decades. As a consequence, the
study of ecological speciation has become an extremely productive research area
in modern evolutionary biology. Recent innovations in sequencing technologies
offer an unprecedented opportunity to study the mechanisms involved in ecological
speciation. Genome scans provide significant insights but have some important
limitations; efforts are needed to integrate them with other approaches to make
full use of the sequencing data deluge. An international conference 'Advances in
Ecological Speciation' organized by the University of Porto (Portugal) aimed to
review current progress in ecological speciation. Using some of the examples
presented at the conference, we highlight the benefits of integrating ecological
and genomic data and discuss different mechanisms of parallel evolution. Finally,
future avenues of research are suggested to advance our knowledge concerning the
role of natural selection in the establishment of reproductive isolation during
ecological speciation.
PMID- 24354650
TI - Inhibitory effects of areca nut extract on expression of complement receptors and
fc receptors in human neutrophils.
AB - BACKGROUND: Chewing of areca quid increases the prevalence of periodontal
diseases. Areca nut extract (ANE) inhibits the phagocytic activity of human
neutrophils. This in vitro study investigates the effects of ANE on complement-
and antibody-opsonized phagocytosis by neutrophils. Expression of complement
receptors, Fc receptors, and F-actin in ANE-treated neutrophils is also analyzed.
METHODS: The viability of ANE-treated neutrophils was determined using the
propidium iodide staining method. The possible effects of ANE on the expression
of complement receptors and Fc receptors were examined using an
immunofluorescence staining method followed by flow cytometry and confocal laser
scanning microscopy. The phagocytic activity of neutrophils against complement or
immunoglobulin (Ig)G-opsonized fluorescent beads was analyzed using flow
cytometry. Expression of F-actin was determined using confocal laser scanning
microscopy. RESULTS: ANE significantly inhibited the production of complement
receptors (CR1, CR3, and CR4) and Fc receptors (FcgammaRII and FcgammaRIII) in a
concentration-dependent manner. Treatment of neutrophils with ANE significantly
impaired their ability to phagocytose fluorescent beads. ANE also inhibited
phagocytosis of fluorescent beads that were opsonized by complement or IgG.
Moreover, expression of F-actin was inhibited after ANE treatment. CONCLUSIONS:
ANE inhibits the complement- and IgG-mediated neutrophil phagocytosis that may
result from reduction of the expression of complement receptors, Fc receptors,
and F-actin formation after ANE treatment. The findings suggest that areca nut
chewing may jeopardize the defensive functions of neutrophils and affect
periodontal health.
PMID- 24354651
TI - Routine prophylaxes every 3 months improves chronic periodontitis status in type
2 diabetes.
AB - BACKGROUND: Periodontitis and type 2 diabetes mellitus (T2DM) are major health
problems, especially in low-income populations with little access to dental care.
Low-cost models for treatment of periodontal disease have not been tested in
controlled studies in low-income populations. Dental prophylaxis, which includes
removal of supragingival calculus and plaque, has been shown to arrest the
progression of periodontitis. A controlled clinical trial was conducted to
determine the effect of dental prophylaxis on periodontitis in T2DM. METHODS:
Twenty-six patients with T2DM and chronic periodontitis (CP) and 26 without T2DM
with CP were selected. Periodontal probing depth (PD), gingival bleeding on
probing (BOP), clinical attachment level (CAL), and surfaces with plaque were
recorded at baseline and 3, 6, and 9 months after initial treatment. All the
participants received instructions on oral hygiene and one session of dental
prophylaxis at baseline and every 3 months. Glycated hemoglobin (HbA1c) levels
were measured at baseline and every 3 months in patients with T2DM. RESULTS: A
significant improvement of PD, BOP, and sites with plaque was observed 3 months
after treatment in patients with T2DM (P = 0.001). In controls, mean PD
significantly improved after 6 months compared with baseline (P = 0.001). No
significant improvement of CAL occurred in either group. No significant
differences in periodontal parameters between the groups were detected, and no
participant showed progression of CP during the 9-month study period. Dental
prophylaxis did not influence HbA1c levels, and no association among HbA1c
concentration, pretreatment metabolic status, and severity of CP was found.
CONCLUSION: Routine prophylaxes every 3 months significantly improve periodontal
health and prevent progression of CP in both poorly controlled and well
controlled patients with T2DM.
PMID- 24354649
TI - Accuracy of self-reported periodontal disease in the Women's Health Initiative
Observational Study.
AB - BACKGROUND: This study examines the accuracy of self-reported periodontal disease
in a cohort of older females. METHODS: The study comprised 972 postmenopausal
females aged 53 to 83 years who completed baseline (1997 to 2001) and follow-up
(2002 to 2006) whole-mouth oral examinations. Examinations included: 1) probing
depth, 2) clinical attachment level, and 3) oral radiographs for alveolar crestal
height in a study ancillary to the Women's Health Initiative Observational Study
(WHI-OS) conducted in Buffalo, New York, called the OsteoPerio study.
Participants also self-reported any history of diagnosis of periodontal/gum
disease on a WHI-OS study-wide questionnaire administered during the time
interval between the two OsteoPerio examinations. RESULTS: Participants reporting
diagnosis of periodontal/gum disease on the WHI-OS questionnaire (n = 259; 26.6%)
had worse oral hygiene habits, periodontal disease risk factors, and clinical
periodontal measures compared with those not reporting periodontal/gum disease.
Frequency of reported periodontal/gum disease was 13.5%, 24.7%, and 56.2% across
OsteoPerio baseline examination categories of none/mild, moderate, and severe
periodontal disease, respectively (trend: P <0.001), defined by criteria of the
Centers for Disease Control and Prevention/American Academy of Periodontology
(CDC/AAP). Sensitivity, specificity, and positive and negative predictive values
for reported periodontal disease status were 56.2%, 78.8%, 32.8%, and 90.7%,
respectively, when CDC/AAP-defined severe periodontal disease at baseline was the
criterion measure (prevalence of 15%) and were 76.0%, 77.4%, 22.0%, and 97.4%,
respectively, when tooth loss to periodontitis (prevalence of 7%) was the
criterion. CONCLUSION: A simple question for self-reported periodontal disease
characterizes periodontal disease prevalence with moderate accuracy in
postmenopausal females who regularly visit their dentist, particularly in those
with more severe disease.
PMID- 24354652
TI - Prepregnancy obesity and periodontitis among pregnant females with and without
gestational diabetes mellitus.
AB - BACKGROUND: This study explored whether there is an association between
prepregnancy obesity and periodontitis among pregnant females. METHODS: A
retrospective cohort study was conducted by using data from a previous case
control study at Woman's Hospital, Baton Rouge, Louisiana. One hundred fifty-nine
pregnant females were recruited at their prenatal care visits. Periodontal status
was assessed through dental examinations performed at an average of 31 weeks
gestation. Periodontitis was defined as the presence of one or more sites
exhibiting probing depth >=4 mm or clinical attachment level >=4 mm. A Poisson
regression with robust error variance was used to estimate risk ratio (RR) and
95% confidence interval (CI). RESULTS: Prepregnancy obesity was statistically
significantly associated with periodontitis during pregnancy, with obese females
at 1.7 times higher risk compared with under/normal-weight females (RR = 1.7, 95%
CI = 1.2 to 2.3, P <0.01). There is no difference in the association between
maternal obesity and periodontitis between females with gestational diabetes
mellitus (GDM) and females without GDM. CONCLUSION: There is a positive
association between prepregnancy obesity and periodontitis among pregnant
females.
PMID- 24354654
TI - Models of gene gain and gene loss for probabilistic reconstruction of gene
content in the last universal common ancestor of life.
AB - BACKGROUND: The problem of probabilistic inference of gene content in the last
common ancestor of several extant species with completely sequenced genomes is:
for each gene that is conserved in all or some of the genomes, assign the
probability that its ancestral gene was present in the genome of their last
common ancestor. RESULTS: We have developed a family of models of gene gain and
gene loss in evolution, and applied the maximum-likelihood approach that uses
phylogenetic tree of prokaryotes and the record of orthologous relationships
between their genes to infer the gene content of LUCA, the Last Universal Common
Ancestor of all currently living cellular organisms. The crucial parameter, the
ratio of gene losses and gene gains, was estimated from the data and was higher
in models that take account of the number of in-paralogs in genomes than in
models that treat gene presences and absences as a binary trait. CONCLUSION:
While the numbers of genes that are placed confidently into LUCA are similar in
the ML methods and in previously published methods that use various parsimony
based approaches, the identities of genes themselves are different. Most of the
models of either kind treat the genes found in many existing genomes in a similar
way, assigning to them high probabilities of being ancestral ("high
ancestrality"). The ML models are more likely than others to assign high
ancestrality to the genes that are relatively rare in the present-day genomes.
PMID- 24354656
TI - An early-phase translation study of the ways to enhance children's activity and
nutrition (We Can!) programme for low-income families.
PMID- 24354655
TI - Sexual communication between early adolescents and their dating partners,
parents, and best friends.
AB - This study assessed early adolescents' sexual communication with dating partners,
parents, and best friends about six sexual health topics: condoms, birth control,
sexually transmitted diseases (STDs), human immunodeficiency virus/acquired
immunodeficiency syndrome (HIV/AIDS), pregnancy, and abstinence/waiting. Using a
school-based sample of 603 youth (ages 12 to 15; 57% female; 46% Caucasian), we
examined communication differences across demographic and developmental factors,
tested whether communication with parents and best friends was associated with
greater communication with partners, and examined associations between
communication and condom use. More than half of participants had not discussed
any sexual topics with their dating partners (54%), and many had not communicated
with parents (29%) or best friends (25%). On average, communication was more
frequent among adolescents who were female, African American, older, and sexually
active, despite some variation in subgroups across partner, parent, and friend
communication. Importantly, communication with parents and friends--and the
interaction between parent and friend communication--was associated with
increased communication with dating partners. Further, among sexually active
youth, increased sexual communication with partners was associated with more
frequent condom use. Results highlight the importance of understanding the
broader family and peer context surrounding adolescent sexual decision making and
suggest a possible need to tailor sexual communication interventions.
PMID- 24354657
TI - Updated molecular epidemiology of carbapenem-non-susceptible Escherichia coli in
Taiwan: first identification of KPC-2 or NDM-1-producing E. coli in Taiwan.
AB - BACKGROUND: The global spread and increasing incidence of carbapenem-resistant
Enterobacteriaceae have resulted in treatment and public health concerns. Here,
we present an investigation of the molecular mechanisms and clonality of
carbapenem-non-susceptible Escherichia coli (CnSEC) based on a nationwide survey
in Taiwan. METHODS: We collected 32 and 43 carbapenem-non-susceptible E. coli
isolates in 2010 and 2012, respectively. The genes encoding cabapenemases and
plasmidic AmpC-type and extended-spectrum beta-lactamases (EBSLs) were analyzed
by polymerase chain reaction (PCR). The major porin channels OmpF and OmpC were
evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
PAGE). Molecular typing was performed with pulsed-field gel electrophoresis
(PFGE) and multi-locus sequence typing (MLST). RESULTS: The resistance rates of
CnSEC isolates to cefazolin, cefotaxime, cefoxitin, ceftazidime, and ertapenem
were all 100%, and most (94.7%) isolates were CMY producers. The main mechanism
of CnSEC in Taiwan is via plasmidic AmpC beta-lactamase CMY-2 and DHA-1 in
combination with the loss of OmpC/F. In 2010, one isolate was confirmed to harbor
blaIMP-8; a KPC-2 producer and an NDM-1 producer were detected in 2012. No
isolate had VIM- or OXA-carbapenemases. ST131 was the predominant ST type
(33.3%). PFGE revealed no large cluster in CnSEC isolates in Taiwan. CONCLUSIONS:
The co-existence of plasmidic AmpC beta-lactamase and outer membrane protein loss
is the main mechanism for CnSEC in Taiwan. The emergence of KPC-2 and NDM-1 in
2012 and the predominance of ST131 warrant close monitoring and infection
control.
PMID- 24354658
TI - Acoustic startle reactivity while processing reward-related food cues during food
deprivation: evidence from women in different menstrual cycle phases and men.
AB - Previous research has shown that food deprivation enhances the acoustic startle
reflex when it is elicited during presentation of visual food cues. Frustrative
nonreward may explain this effect, since visual food cues are also rated to be
more appetitive and arousing during food deprivation. However, the impact of
menstrual cycle and sex on this effect remains unclear, and it is also not known
whether this effect is influenced by hunger and motivation to eat. According to a
within-study design, 20 healthy women in different menstrual cycle phases and 14
healthy men participated twice, in normal and food-deprived conditions. After 18
h of food deprivation, acoustic startle was attenuated by appetitive nonfood
foreground pictures, but enhanced by presentation of food pictures. No
differences between menstrual cycle phases and sexes appeared. The effect
correlated with hunger changes, suggesting that motivational factors play a role.
PMID- 24354659
TI - Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase
III trials.
AB - INTRODUCTION: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon
after, it was established that blockade of dopamine and, in particular, the D2
receptor was central to this effect. Dopamine continues to represent a critical
line of investigation, although much of the work now focuses on its potential in
other symptom domains. AREAS COVERED: A search was carried out for
investigational drugs using the key words 'dopamine', 'schizophrenia' and 'Phase
III' in an American clinical trial registry (clinicaltrials.gov), published
articles using the National Library of Medicine's PubMed database, and
supplemented results with a manual search of cross-references and conference
abstracts. Drugs were excluded that were already FDA approved. EXPERT OPINION:
There remains interest, albeit diminished, in developing better antipsychotic
compounds. The greatest enthusiasm currently centres on dopamine's role in
negative and cognitive symptom domains. With theories conceptualising
hypodopaminergic activity as underlying these deficits, considerable effort is
focused on drug strategies that will enhance dopamine activity. Finally, a small
body of research is investigating dopaminergic compounds vis-a-vis side-effect
treatments. In domains beyond psychosis, however, dopamine arguably is not seen
as so central, reflected in considerable research following other lines of
investigation.
PMID- 24354653
TI - Guidelines on the use of extracorporeal photopheresis.
AB - BACKGROUND: After the first investigational study on the use of extracorporeal
photopheresis for the treatment of cutaneous T-cell lymphoma was published in
1983 with its subsequent recognition by the FDA for its refractory forms, the
technology has shown significant promise in the treatment of other severe and
refractory conditions in a multi-disciplinary setting. Among the major studied
conditions are graft versus host disease after allogeneic bone marrow
transplantation, systemic sclerosis, solid organ transplant rejection and
inflammatory bowel disease. MATERIALS AND METHODS: In order to provide recognized
expert practical guidelines for the use of this technology for all indications
the European Dermatology Forum (EDF) proceeded to address these questions in the
hands of the recognized experts within and outside the field of dermatology. This
was done using the recognized and approved guidelines of EDF for this task.
RESULTS AND CONCLUSION: These guidelines provide at present the most
comprehensive available expert recommendations for the use of extracorporeal
photopheresis based on the available published literature and expert consensus
opinion.
PMID- 24354660
TI - Immunogenicity of bacterial-expressed recombinant Plasmodium knowlesi merozoite
surface protein-142 (MSP-142).
AB - BACKGROUND: Plasmodium knowlesi is the fifth Plasmodium species that can infect
humans. The Plasmodium merozoite surface protein-1(42) (MSP-1(42)) is a potential
candidate for malaria vaccine. However, limited studies have focused on P.
knowlesi MSP-1(42). METHODS: A ~42 kDa recombinant P. knowlesi MSP-1(42) (pkMSP
1(42)) was expressed using an Escherichia coli system. The purified pkMSP-1(42)
was evaluated with malaria and non-malaria human patient sera (n = 189) using
Western blots and ELISA. The immunogenicity of pkMSP-1(42) was evaluated in mouse
model. RESULTS: The purified pkMSP-1(42) had a sensitivity of 91.0% for detection
of human malaria in both assays. Specificity was 97.5 and 92.6% in Western blots
and ELISA, respectively. Levels of cytokine interferon-gamma, interleukin-2,
interleukin-4, and interleukin-10 significantly increased in pkMSP-1(42)
immunized mice as compared to the negative control mice. pkMSP-1(42)-raised
antibody had high endpoint titres, and the IgG isotype distribution was IgG1 >
IgG2b > IgG3 > IgG2a. CONCLUSIONS: pkMSP-1(42) was highly immunogenic and able to
detect human malaria. Hence, pkMSP-1(42) would be a useful candidate for malaria
vaccine development and seroprevalence studies.
PMID- 24354661
TI - Rhamsan gum production by Sphingomonas sp. CGMCC 6833 using a two-stage agitation
speed control strategy.
AB - Varying the agitation speed could greatly affect rhamsan gum production by
Sphingomonas sp. CGMCC 6833. Batch fermentations at agitation speeds of 400, 600,
800, and 1,000 rpm were therefore carried out. The time course of specific cell
growth rate, specific glucose consumption rate, and specific rhamsan gum
formation rate was subsequently determined. Based on the results, a novel two
stage agitation speed control strategy was developed. From 0 to 13 H, the high
specific cell growth and glucose consumption rates were achieved by setting the
agitation speed of the fermenter at 800 rpm. From 13 H onward to the end of
fermentation, the glucose consumption rate and specific cell growth rate were
high at the agitation speed of 600 rpm. Using this method, the maximum
concentration and productivity of rhamsan gum reached 21.63 +/- 1.76 g L(-1) and
0.338 +/- 0.028 g L(-1) H(-1) , respectively, which were both higher than the
optimum results obtained at constant agitation speeds.
PMID- 24354663
TI - Giant atypical lipoma of the thigh.
PMID- 24354662
TI - Greater externalizing personality traits predict less error-related insula and
anterior cingulate cortex activity in acutely abstinent cigarette smokers.
AB - Attenuated activity in performance-monitoring brain regions following erroneous
actions may contribute to the repetition of maladaptive behaviors such as
continued drug use. Externalizing is a broad personality construct characterized
by deficient impulse control, vulnerability to addiction and reduced
neurobiological indices of error processing. The insula and dorsal anterior
cingulate cortex (dACC) are regions critically linked with error processing as
well as the perpetuation of cigarette smoking. As such, we examined the
interrelations between externalizing tendencies, erroneous task performance, and
error-related insula and dACC activity in overnight-deprived smokers (n = 24) and
non-smokers (n = 20). Participants completed a self-report measure assessing
externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker
task during functional magnetic resonance imaging scanning. We observed that
higher externalizing tendencies correlated with the occurrence of more
performance errors among smokers but not non-smokers. Suggesting a
neurobiological contribution to such suboptimal performance among smokers, higher
externalizing also predicted less recruitment of the right insula and dACC
following error commission. Critically, this error-related activity fully
mediated the relationship between externalizing traits and error rates. That is,
higher externalizing scores predicted less error-related right insula and dACC
activity and, in turn, less error-related activity predicted more errors.
Relating such regional activity with a clinically relevant construct, less error
related right insula and dACC responses correlated with higher tobacco craving
during abstinence. Given that inadequate error-related neuronal responses may
contribute to continued drug use despite negative consequences, these results
suggest that externalizing tendencies and/or compromised error processing among
subsets of smokers may be relevant factors for smoking cessation success.
PMID- 24354664
TI - Sequestration of rhBMP-2 into self-assembled polyelectrolyte complexes promotes
anatomic localization of new bone in a porcine model of spinal reconstructive
surgery.
AB - Efficient and therapeutically safe delivery of recombinant human bone
morphogenetic protein 2 (rhBMP-2) continues to be a central issue in bone tissue
engineering. Recent evidence indicates that layer-by-layer self-assembly of
polyelectrolyte complexes (PECs) can be used to recreate synthetic matrix
environments that would act as tuneable reservoirs for delicate biomolecules and
cells. Although preliminary in vitro as well as small-animal in vivo studies
support this premise, translation into clinically relevant bone defect volumes in
larger animal models remains unreported. Here we explored the use of native
heparin-based PEC, deposited on a hydrated alginate gel template, to load
bioactive rhBMP-2 and to facilitate lumbar interbody spinal fusion in pigs. We
observed that triple PEC deposits with the highest protein sequestration
efficiency and immobilization capacity promoted higher volume of new bone
formation when compared with single PEC with low sequestration efficiency and
immobilization capacity. This also resulted in a significantly enhanced
biomechanical stability of the fused spinal segment when compared with PEC
carriers with relatively low protein sequestration and immobilization capacities
(p<0.05). Most importantly, PEC carriers showed a more orderly pattern of new
bone deposition and superior containment of bone tissue within implant site when
compared to collagen sponge carriers. We conclude that this growth factor
sequestration platform is effective in the healing of clinically relevant bone
defect volume and could overcome some of the safety concerns and limitations
currently associated with rhBMP-2 therapy such as excessive heterotopic
ossification.
PMID- 24354665
TI - Amidation reactions from the direct coupling of metal carboxylate salts with
amines.
AB - A general method for the synthesis of amides involving the direct coupling of
alkali metal carboxylate salts with amines is described. Amidation of a wide
variety of carboxylate salts with either free amines or their ammonium
hydrochloride salts can be achieved using HBTU as a coupling agent in combination
with Hunig's base. The reaction is highly efficient and is generally complete in
as little as 1-2 h, giving the products in good to excellent yields. The protocol
is valuable for the coupling of carboxylates for which the corresponding
carboxylic acids or acyl chlorides are unstable, less conveniently
manipulated/isolated, or are not commercially available. For example, the
coupling of amines and alpha-amino acids with lithium 5-bromo-1H-pyrrole-2
carboxylate, whose corresponding acid that is prone to decarboxylation, allowed
for the synthesis of 5-bromo-1H-pyrrole-2-carboxamides, which are analogues of
the pyrrole-2-aminoimidazole marine alkaloids. The protocol can be combined with
other reactions in a sequenced fashion, as exemplified by the synthesis of
acetylenic amides, in a one-pot procedure, via the coupling of a lithium
carboxylate salt formed initially by the addition of carbon dioxide to a
lithiated terminal alkyne.
PMID- 24354666
TI - Cyclodextrin-based polysaccharidic polymers: an approach for the drug delivery.
AB - The aim of the present review is to give an overview of a new class of
polysaccharidic CD-based systems and to address the use of these systems in drug
delivery. First, we review miscellaneous methods to obtain and synthesize the
structural modification of natural polysaccharides, mainly, with cyclodextrins.
In a second part of this review, we provide a summary of recent findings not only
in the field of drug delivery, but in also how these systems have displayed
different applications in the biomedical and pharmaceutical fields.
PMID- 24354667
TI - Progress in developing amphiphilic cyclodextrin-based nanodevices for drug
delivery.
AB - Nowadays, colloidal drug carriers represent an alternative to solve drug
bioavailabily problems. During the past two decades, colloidal drug carriers have
proved to improve the therapeutic index of drugs and thus increase their efficacy
and/or reduce their toxicity. However, the major challenge in the development of
these drug carriers remains the search for materials able to self-organize into
stable nanoscale systems. In particular, amphiphilic alpha-, beta- and gamma
cyclodextrins (CDs), grafted on their secondary or primary side with different
aliphatic chains, have been investigated as drug delivery vehicles due to their
ability to self-assemble and form various stable colloidal systems such as
micellar aggregates, nanoreservoirs or nanoparticles exhibiting a matricial,
multilamellar or hexagonal supramolecular organization. These self-assembled CD
based nanodevices show some advantages in terms of stability, good ability to
associate lipophilic drugs and good in vivo tolerance. This review focuses on the
potential of the structured nanoparticles obtained from nonionic amphiphilic CDs
in drug delivery and targeting. We discuss the synthesis and characterization of
the building blocks as well as the preparation and characterization of colloidal
particles made from these materials. We also considered some pharmaceutical
applications and identified opportunities for an optimum use of this CD-based
nanotechnology approach in addressing worldwide priority health problems.
PMID- 24354668
TI - Cyclodextrin inclusion complexes loaded in particles as drug carrier systems.
AB - This mini-review paper does not consider classical work concerning the formation
of inclusion complexes between pharmaceuticals and cyclodextrins. Instead, it
highlights recent reports concerning the association of these host:guest systems
with other carrier systems such as liposomes and nanoparticles showing the state
of art of this subject with examples of developed systems and the advantages of
these strategy in order to be potential systems as drug carriers.
PMID- 24354669
TI - Oil-cyclodextrin based beads for oral delivery of poorly-soluble drugs.
AB - The main interest of cyclodextrins results from their ability to form inclusion
complexes with hydrophobic molecules. This property is employed in pharmaceutical
industry to facilitate the formulation of poorly-soluble and/or fragile drugs.
Cyclodextrins are also used to form or stabilise dispersed systems. An original
multiparticulate system named "beads" is obtained thanks to the interactions
occurring between the molecules of alpha cyclodextrin and the triglycerides of
vegetable oils. Beads are prepared by a simple process involving the external
shaking of a mixture of an aqueous solution of alpha cyclodextrin with soybean
oil. This is done without any organic solvent or surface-active agent. Once
freezedried, beads have a diameter of 1.6 mm and a high lipid content. They
consist in a partially crystalline matrix of cyclodextrin surrounding
microdomains of oil. The coating of beads with a layer of alpha cyclodextrin
improves their resistance in gastro- intestinal fluids and prolongs the release
of drugs. Beads can also be manufactured from mineral oils with alpha
cyclodextrin and from silicone oils with gamma cyclodextrin. Poorly-soluble drugs
which do not form inclusion complexes with alpha cyclodextrin are encapsulated in
beads with high efficiency and drug loading. In rats, the oral bioavailability of
isotretinoin is twofold enhanced with uncoated beads as compared to the lipid
content of a soft capsule. The relative oral bioavailability of indomethacin is
improved with both coated and uncoated beads versus a commercial hard capsule.
Beads demonstrate an important potential for the encapsulation of poorly-soluble
and/or fragile compounds and their delivery by oral route.
PMID- 24354670
TI - Syringeable self-assembled cyclodextrin gels for drug delivery.
AB - The design of syringeable cyclodextrin (CD) gels is a developing area in the drug
delivery and tissue engineering fields, since they offer the possibility of being
administered with minimally invasive maneuvers to form depots that can remain for
prolonged time in the implantation site. Two different supramolecular systems can
be obtained exploiting the capability of CDs to form inclusion complexes. (i) The
threading of free CDs on certain blocks or side chains of copolymers leads to
polypseudorotaxanes, which can assembly via regular stacking of the threaded CDs.
The resultant assemblies can be reversible broken under a certain shear stress
and reformed at rest, exhibiting thixotropy that enables the flow through the
syringe and the gel recovery in the implantation site. (ii) CDs grafted to
polymer chains can develop their ability to form inclusion complexes with
complementary guest moieties in other polymeric structures. The result is a
ladder- or zipper-like arrangement, which can be also broken and reformed under
certain stress conditions. Both types of CDsupramolecular gels can load and
stabilize a variety of drugs via interaction with available polymer functional
groups or with the CDs that are not participating in other complexes. Moreover,
since the complex formation depends on various external and internal variables of
the body, the syringeable CD gels can also provide stimuli-responsive drug
release. This review focuses on the two main types of syringeable CD gels,
prepared via self-aggregation of poly(pseudo)rotaxanes and via zipper-like
assembly of CD-functionalized and guest-functionalized macromolecules, and
analyzes the mechanisms and variables involved in the gelling processes and the
most recent applications in the drug delivery field.
PMID- 24354671
TI - Cyclodextrin based rotaxanes, polyrotaxanes and polypseudorotaxanes and their
biomedical applications.
AB - For years, great efforts have been made by scientists to construct various novel
interlocked supramolecular systems. A wide range of pseudorotaxanes and
rotaxanes, full of challenging constructions and potential applications in areas
such as nanostructured functional materials, molecular switches, molecular logic
gates, molecular wires, memory devices Willner and biomedical applications have
been reported recently. Cyclodextrin polyrotaxantes or polypseudorotaxanes there
are not only nice and interesting supramolecular architectures but they also have
a high interest for biomaterials application that allow to opened up new
approaches for tissue regeneration, drug and gene delivery. The use of the
supramolecular cyclodextrins complexes has given rise to interesting studies to
design and develop new biomaterials with advanced properties. In this review we
will update the recent advances in the use of CDs-supramolecular structures for
develop new and advanced drug and gene delivery systems and for use in tissue
engineering.
PMID- 24354672
TI - Cyclodextrin/Dendrimer conjugates as DNA and oligonucleotide carriers.
AB - Recently, various cyclodextrin (CyD)-grafted polymers and supramolecules have
been developed as gene and oligonucleotide carriers. We have demonstrated that
among the various polyamidoamine starburst(TM) dendrimers (dendrimers) conjugates
with CyDs (CDEs), the dendrimer (G2 or G3) conjugate with alpha-CyD showed high
gene and oligonucleotide transfer activity with negligible cytotoxicity. In
addition, to develop tissue- or cell-specific gene transfer carriers, we also
prepared alpha-CDEs modified with functional molecules, such as mannose, fucose,
galactose, lactose, polyethylene glycol (PEG) and folate-PEG. Moreover,
polypseudorotaxane-appended alpha-CDEs were developed as sustained release
systems for DNA and siRNA. Interestingly, glucronylglucosyl-beta-CyD conjugates
with dendrimer (G2) (GUG-beta-CDE (G2)) showed high gene transfer activity
compared to alpha-CDE (G2) and beta-CDE (G2). In this review, we focus on the
potential use of various CDEs as DNA and oligonucleotide transfer carriers.
PMID- 24354673
TI - Natural & synthetically-modified cyclodextrins and polymers in drug delivery
systems.
AB - Cyclodextrins are natural cyclic oligosaccharides that play a relevant role in
different fields as pharmacy, medicine, chemistry, material, food or agricultural
science. From the point of view of pharmaceutical and medical applications
cyclodextrins have interest for their ability to form inclusion complexes with
different host molecules as drugs. In the pharmaceutical industry, cyclodextrins
has been used classically as solubilizes of hydrophobic drugs or as stabilizers
of some labile molecules but can also offer interesting possibilities for drug
control release of both hydrophobic and hydrophilic drugs. New and interesting
perspectives for their use is being developed in recent years by the development
of novel cyclodextrin derivatives including the polymeric one. The proposed topic
for this special number of CTMC aims to provide new successes, challenges and
recent advances on the design and applications of new CDs derivatives into the
biomedical and pharmaceutical field .
PMID- 24354674
TI - Lower serum sodium level predicts higher risk of infection-related
hospitalization in maintenance hemodialysis patients: an observational cohort
study.
AB - BACKGROUND: Hyponatremia is associated with increased mortality in chronic kidney
disease with and without end-stage renal disease (ESRD). Increasing evidence
suggests that hyponatremia is not only a marker of severe underlying disease, but
also a direct contributor to mortality. However, specific pathogenesis or
diseases contributing to mortality in the hyponatremic population are unknown.
This study aimed to clarify the relationship between serum sodium level (sNa) and
infection risk in ESRD patients. METHODS: This observational cohort study
included 332 patients on maintenance hemodialysis in our dialysis unit in May
2009. The mean of 3 monthly measurements of glucose-corrected sNa before each
dialysis session in May, June, and July 2009 was applied as baseline sNa. The
primary endpoint was first infection-related hospitalization (IRH), and the
secondary endpoint was death of any cause. Data were analyzed using Cox hazards
modeling, adjusted for baseline demographics and characteristics, or laboratory
data. Patients were followed until transfer, kidney transplantation, death, or
study end on January 31, 2013. RESULTS: Mean sNa was 138.9 mEq/L (1st tertile:
<138.0, n = 104; 2nd tertile: 138.0-140.0, n = 116; 3rd tertile: >140.0, n =
112). During 39.5 months' mean follow-up, 57 patients experienced IRH (56.4/1,000
patient-years overall; 89.7/1,000 in 1st tertile; 57.9/1,000 in 2nd tertile;
28.0/1,000 in 3rd tertile), and 68 patients died. The hazard ratio (HR) for IRH
was higher for the 1st and 2nd tertiles than the 3rd tertile (unadjusted HR,
3.20; 95% confidence interval (CI), 1.54-6.64; p = 0.002; adjusted HR, 2.36; 95%
CI, 1.10-5.04; p = 0.027; and unadjusted HR, 2.07; 95% CI, 0.98-4.40; p = 0.058;
adjusted HR, 2.11; 95% CI, 0.99-4.51; p = 0.054 respectively). In a continuous
model, higher sNa was associated with lower risk of IRH (adjusted HR, 0.90; 95%
CI, 0.81-0.99; p = 0.040), and lower all-cause mortality (adjusted HR, 0.91; 95%
CI, 0.83-1.00; p = 0.049). CONCLUSIONS: Lower sNa is an independent predictor of
higher risk for infection-related hospitalization in maintenance hemodialysis
patients. Infectious disease may partially account for the increased mortality
observed in the hyponatremic population with ESRD.
PMID- 24354676
TI - Promiscuity resolves constraints on social mate choice imposed by population
viscosity.
AB - Population viscosity can have major consequences for adaptive evolution, in
particular for phenotypes involved in social interactions. For example,
population viscosity increases the probability of mating with close kin,
resulting in selection for mechanisms that circumvent the potential negative
consequences of inbreeding. Female promiscuity is often suggested to be one such
mechanism. However, whether avoidance of genetically similar partners is a major
selective force shaping patterns of promiscuity remains poorly supported by
empirical data. Here, we show (i) that fine-scale genetic structure constrains
social mate choice in a pair-bonding lizard, resulting in individuals pairing
with genetically similar individuals, (ii) that these constraints are
circumvented by multiple mating with less related individuals and (iii) that this
results in increased heterozygosity of offspring. Despite this, we did not detect
any significant effects of heterozygosity on offspring or adult fitness or a
strong relationship between pair relatedness and female multiple mating. We
discuss these results within the context of incorporating the genetic context
dependence of mating strategies into a holistic understanding of mating system
evolution.
PMID- 24354675
TI - Effect of Korean red ginseng on cold hypersensitivity in the hands and feet:
study protocol for a randomized controlled trial.
AB - BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is one of the most
common complaints among Asians, especially in women. Korean red ginseng (KRG),
which is a steamed form of Panax ginseng, has vasodilating action in the
peripheral vessels and increases blood flow under cold stress. However, few
studies have evaluated the effect of KRG on cold hypersensitivity.
METHODS/DESIGN: This trial is a randomized, double-blind, placebo-controlled
trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University
Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo
for eight weeks, after which they will be followed-up for four weeks. During the
administration period, six capsules of 500 mg KRG or placebo will be provided
twice a day. The primary outcome is change of skin temperature in the hands
between baseline and after treatment. The secondary outcomes include the visual
analogue scale scores of cold hypersensitivity in the hands, change of skin
temperature and the VAS scores of cold hypersensitivity in the feet, the recovery
rate of the skin temperature by the cold stress test of the hands, the distal
dorsal difference of the hands, power variables of heart rate variability, and
the 36-item short form health survey. DISCUSSION: This study is the first trial
to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study
will provide basic evidence regarding CHHF. TRIAL REGISTRATION:
CliniacalTrials.gov NCT01664156.
PMID- 24354677
TI - The effects of flanking sequences in the interaction of polyglutamine peptides
with a membrane bilayer.
AB - Huntington's disease (HD) is caused by the presence of an extended polyglutamine
(polyQ) region at the N-terminus of the huntingtin (htt) protein. The presence of
flanking sequences adjacent to the polyQ region has been reported to modulate the
effects of potentially toxic protein-membrane interactions. In this study, we
consider four peptide systems with various combinations of flanking sequences
(KKQ35KK, KKQ35P11KK, N17Q35KK, N17Q35P11KK) and use atomistic molecular dynamics
simulations to study the interactions with a DOPC lipid bilayer. We observe
significant membrane thinning, disorderliness of lipid molecules, and
compensation effects between the top and the bottom leaflets of the bilayer
depending on the presence of particular flanking sequences. Overall, we find that
the presence of the N-17 flanking sequence is crucial for membrane interactions.
Polyproline decreases the interaction with the membrane in the absence of N-17,
but enhances it when present along N-17.
PMID- 24354678
TI - Ruxolitinib for pulmonary extramedullary hematopoiesis in myelofibrosis.
PMID- 24354679
TI - The identity crisis of Kruppel-like factor 4.
PMID- 24354680
TI - Expression and subcellular localization of cyclin-dependent kinase inhibitor p27
does not correlate with proliferation pattern of mantle lymphoma cells.
PMID- 24354681
TI - Radiation therapy for early stage unfavorable Hodgkin lymphoma: is dose reduction
feasible?
AB - One hundred and fifty-one patients aged between 3 and 70 years with early stage
unfavorable Hodgkin lymphoma were included. Patients received 4-6 cycles of ABVD
(doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and involved
field radiation therapy (IFRT). The most common histology was mixed cellularity
(43%). The majority had stage IIAX disease. IFRT doses were 25.2 Gy/14 fractions
and 34.2 Gy/19 fractions for adults with a complete response (CR) and partial
response (PR), respectively, while the doses were 19.8 Gy/11 fractions and 30.6
Gy/17 fractions, respectively, for children. After 60 months (median), the 10
year progression-free survival (PFS) and overall survival (OS) were 88.4% and
93.2%, respectively. On univariate analysis, prognostic factors with significant
impact on PFS were age >= 18 years, nodular lymphocyte-predominant Hodgkin
lymphoma (NLPHL) histology, extranodal disease and response to treatment.
Extranodal disease had a significant impact on OS. On multivariate analysis,
NLPHL histology (p = 0.001) and response at 3 months (p = 0.000) had a
significant impact on PFS. There were no in-field relapses in patients with bulky
disease receiving RT doses > 25.2 Gy. Chemotherapy related acute pulmonary
toxicity was documented in 21.4% and 4.8% of patients after six and four cycles
of ABVD chemotherapy (p = 0.041). Four cycles of ABVD and reduced dose IFRT
resulted in optimal outcomes.
PMID- 24354682
TI - Impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography
staging in newly diagnosed classical Hodgkin lymphoma: fewer cases with stage I
disease and more with skeletal involvement.
AB - (18)F-Fluorodeoxyglucose positron emission tomography/ computed tomography
(PET/CT) is a highly accurate staging method in classical Hodgkin lymphoma (cHL).
We retrospectively compared the staging results obtained in two large cohorts of
patients with cHL diagnosed before (n = 324) and after (n = 406) the introduction
of PET/CT staging in a retrospective study. In PET/CT staged patients, stage I
disease was less frequent (16% vs. 27%, p < 0.001) while stage IV disease was
more frequent (17% vs. 10%, p = 0.02). Imaging-detected skeletal involvement was
recognized more often in PET/CT staged patients (17% vs. 2%, p < 0.001), and the
presence of focal skeletal PET/CT lesions was associated with higher risk of
progression (hazard ratio [HR] 1.96, 95% confidence interval [CI]: 1.14-3.36).
The German Hodgkin Study Group (GHSG) risk classification (early, intermediate,
advanced disease) predicted outcome in PET/CT staged patients. In conclusion,
PET/CT led to higher disease stages, and the more frequently diagnosed skeletal
lesions may be an adverse prognostic factor.
PMID- 24354683
TI - Evaluation of comorbidity indexes in the outcome of elderly patients treated for
acute lymphoblastic leukemia.
PMID- 24354684
TI - Oligoclonal and monoclonal bands after single autologous stem cell transplant in
patients with multiple myeloma: impact on overall survival and progression-free
survival.
AB - Abstract Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB)
unrelated to the original clone has been reported in patients with multiple
myeloma who undergo autologous stem cell transplant (ASCT) and/or receive
treatment with novel agents. The aim of our study was to assess the impact of
OB/MB occurrence on overall (OS) and progression-free survival (PFS) for patients
with MM undergoing single ASCT at our institution. All consecutive patients with
documented MM undergoing single ASCT from January 2000 to December 2012 were
evaluated. Ninety-nine patients (11.8%) developed OB/MB at day 100 post-ASCT
(32.3%, OB and 67.7%, MB). Multivariate analysis identified the development of
OBs/MBs as an independent favorable prognostic factor for OS and PFS (p = 0.008
and 0.012, respectively). In conclusion, the occurrence of OB/MB is an important
prognostic factor in patients with MM who undergo ASCT. Its impact on clinical
outcomes should be prospectively validated and its biological significance
further elucidated.
PMID- 24354685
TI - Cerebrospinal fluid analysis by flow cytometry in acute lymphoblastic leukemia:
is it all that it is cracked up to be?
PMID- 24354686
TI - The influence of resilient liner and clip attachments for bar-implant-retained
mandibular overdentures on opposing maxillary ridge. A 5-year randomised clinical
trial.
AB - This study aimed to compare the influence of resilient liner and clip attachments
for bar-implant-retained mandibular overdentures on opposing maxillary ridge
after 5 years of denture wearing. Thirty edentulous male patients (mean age 62.5
years) received two implants in the anterior mandible after being allocated into
two equal groups using balanced randomisation. After 3 months, implants were
connected with resilient bars. New maxillary complete dentures were then
constructed, and mandibular overdentures were retained to the bars with either
clips (group I, GI) or silicone resilient liners (group II, GII). The prosthetic
and soft tissue complications of the maxillary dentures were recorded 6 months
(T6 m ), 1 year (T1), 3 years (T3) and 5 years (T5) after overdenture insertion.
Traced rotational tomograms were used for measurements of maxillary alveolar bone
loss. The proportional value between bone areas and areas of reference not
subject to resorption was expressed as a ratio (R). Change in R immediately
before (T0) and after 5 years (T5) of overdenture insertion was calculated.
Maxillary denture relining times and frequency of flabby anterior maxillary ridge
occurred significantly more often in GI compared with GII. The change of R in
anterior part of maxilla was significantly higher than change of R in posterior
part in both groups. GI showed significant resorption of anterior residual ridge
compared with GII. Relining times and frequencies of flabby ridge were
significantly correlated with change in R. Within the limitations of this study,
resilient liner attachments for bar-implant-retained mandibular overdentures are
associated with decreased resorption and flabbiness of maxillary anterior
residual ridge and fewer maxillary denture relining times when compared with clip
attachments.
PMID- 24354687
TI - Elaborated contextual framing is necessary for action-based attitude acquisition.
AB - Although arm flexion and extension have been implicated as conditioners of
attitudes, recent work casts some doubt on the nature and strength of the
coupling of these muscle contractions and stimulus evaluation. We propose that
the elaborated contextual framing of flexion and extension actions is necessary
for attitude acquisition. Results showed that when flexion and extension were
disambiguated via elaborated contextual cues (i.e., framed as collect and discard
within a foraging context), neutral stimuli processed under flexion were liked
more than neutral stimuli processed under extension. However, when unelaborated
framing was used (e.g., mere stimulus zooming effects), stimulus evaluation did
not differ as a function of muscle contractions. These results suggest that
neither arm contractions per se nor unelaborated framings are sufficient for
action-based attitude acquisition, but that elaborated framings are necessary.
PMID- 24354688
TI - Motives and decisions for and against having children among nonheterosexuals and
the impact of experiences of discrimination, internalized stigma, and social
acceptance.
AB - Same-sex parents are increasingly a topic of public discourse. A growing number
of homosexuals openly speak about their desire to have children or are already
living together in different family constellations. The current study examined
the decisions for or against having children and the motivations behind those
decisions among nonheterosexuals living in Germany. A sample of 1,283
nonheterosexuals participated by means of an online survey. As some
nonheterosexual individuals do not identify themselves with a male or female
gender identity, a third category, "gender different," was generated. Motives for
(not) having children, perceptions of social acceptance, experiences of
discrimination in relation to one's sexual orientation, and levels of
internalized stigma were taken into account regarding their influence on the
decision about parenthood. Most respondents (80%) reported that they did not have
children. However, among this group, 43% stated that they had decided to have
children later in their lives, 24% were undecided, and 11% had already decided
against having children. The most important influences on the decision of whether
to have children were respondents' age and their desire for emotional
stabilization. Negative experiences as a result of sexual orientation and
internalized stigma had no impact on the decisions regarding parenthood.
PMID- 24354689
TI - Thirty-six cases of epidemic infections due to Trichophyton violaceum in Siena,
Italy.
AB - Trichophyton violaceum is an anthropophilous dermatophyte endemic to parts of
Africa and Asia, sporadic in Europe. It is an emerging pathogen in Italy due to
immigration. We report 36 cases of infections due to T. violaceum, diagnosed in
the last 5 years by mycological examination. The source of contagion was 13
children adopted from orphanages.
PMID- 24354691
TI - Fundamental movement skills and weight status in British primary school children.
AB - Weight status has been shown to have a negative impact on children's competence
in performing fundamental movement skills (FMSs). Following ethics approval and
informed consent, 281 children in years 2-6 from a school in central England
volunteered to participate. Each child performed eight FMSs (run, hop, gallop,
jump, balance, kick, throw and catch) three times, all attempts were video
recorded. Video analysis was performed (Quintic Biomechanics software) using the
Process Orient Checklist (subjective measurement). Height and weight were
measured to calculate body mass index (BMI) and weight status was determined.
Results highlighted that year group (age) had a significant effect on seven out
of the eight skills (not kick). Year 4 (aged 8-9 years) significantly scored
lower in all three locomotor skills (run, hop and gallop) at this age, whereas
Year 5 (aged 9-10 years) all significantly peaked at the object control skills
(catch and throw) at this age. Weight status (BMI) significantly affected the
run, identifying that a child with a larger BMI will have a lower mastery level
of the run. Gender significantly affected the kick, throw and balance, with girls
outperforming in the balance and the boys in the kick and throw. By highlighting
that children at different ages will have a lower score in different skills, the
effect of BMI and gender on certain FMS is important knowledge for the target of
intervention in primary school children.
PMID- 24354690
TI - The first transcriptome and genetic linkage map for Asian arowana.
AB - Asian arowana or dragonfish (Scleropages formosus) is an important fish species
due to its unusual breeding biology and high economic value in the ornamental
fish markets. In the present study, we aimed to (i) create the first
transcriptome by Roche 454 pyrosequencing of Asian arowana brain and gonad
samples; (ii) identify differentially expressed genes between the two sexes and
develop microsatellite (SSR) markers; and (iii) construct a first-generation SSR
based genetic linkage map. A total of over 1.3 million reads were obtained from
the brain and gonad of adult Asian arowana individuals through pyrosequencing.
These reads were assembled into 16,242 contigs that were further grouped into
13,639 isogroups. BLASTX annotation identified a total of 8316 unique proteins
from this data set. Many genes with sexually dimorphic expression levels and some
putatively involved in sex development were identified. A total of 316 EST-SSRs
and 356 new genomic-SSRs were developed by screening through the current
transcriptome data set and SSR-enriched genomic libraries. The first genetic
linkage map of the species was constructed based on these markers. Linkage
analysis allowed for mapping of 308 markers to 28 linkage groups (LGs), ranging
in size from 14.9 to 160.6 cM. The potentially sex-associated gene sox9 was
mapped to LG4 on the consensus linkage map. Pairwise putative conserved syntenies
between the Asian arowana, zebrafish, and three-spined stickleback were also
established. These resources will help the conservation of the species through
better understanding of its phylogenetics, genomics and biology, and comparative
genome analysis within the Osteoglossidae family.
PMID- 24354692
TI - Research on the relationship between fibrinogen level and subtypes of the TOAST
criteria in the acute ischemic stroke.
AB - BACKGROUND: Cerebral infarction caused by different reasons seems differ in
fibrinogen levels, so the current work intends to explore the relationship
between the fibrinogen level and subtypes of the TOAST criteria in the acute
stage of ischemic stroke. METHODS: A total of 577 case research objects were
treated acute ischemic stroke patients in our hospital from December 2008 to
December 2010, and blood samples within 72 hours of the onset were processed with
the fibrinogen (PT-der) measurement. Classification of selected patients
according to the TOAST Criteria was conducted to study the distribution of
fibrinogen levels in the stroke subtypes. RESULTS: The distribution of fibrinogen
levels in the subtypes was observed to be statistically insignificant.
CONCLUSIONS: In the acute stage of ischemic stroke, fibrinogen level was not
related to the subtypes of the TOAST criteria.
PMID- 24354693
TI - Verrucous carcinoma arising in an extended giant condyloma acuminatum (Buschke
Lowenstein tumor): a case report and review of the literature.
AB - INTRODUCTION: Verrucous carcinoma of the external genitalia and perianal region
is a rare variant of well-differentiated squamous cell carcinoma. It has been
reported to have limited metastatic potential. CASE PRESENTATION: We report the
case of a 54 year-old Moroccan man who presented with locally advanced giant
condyloma acuminatum (Buschke-Lowenstein tumor) after prolonged intervals of
neglect (approximately 10 years). The disease covered his suprapubic, external
genitalia and perianal region. It was locally aggressive with extensive tissue
destruction. After a biopsy of the lesion, the diagnosis of verrucous carcinoma
was confirmed. He initially received chemoradiotherapy, followed by extensive
local excision, but he developed septic shock and died a few days later.
CONCLUSIONS: The purpose of this case report is to present a case of verrucous
carcinoma arising in an extensive giant condyloma acuminatum (Buschke-Lowenstein
tumor) and discuss the literature on its diagnosis and management.
PMID- 24354694
TI - Could treatment with R-HCVAD/R-MA as compared to R-CHOP truly result in improved
outcomes for patients with high-risk diffuse large B cell lymphoma?
PMID- 24354695
TI - Are dual eligibles admitted to poorer quality skilled nursing facilities?
AB - BACKGROUND: Dual eligibles, persons who qualify for both Medicare and Medicaid
coverage, often receive poorer quality care relative to other Medicare
beneficiaries. OBJECTIVES: To determine whether dual eligibles are discharged to
lower quality post-acute skilled nursing facilities (SNFs) compared with Medicare
only beneficiaries. RESEARCH DESIGN: Following the random utility maximization
model, we specified a discharge function using a conditional logit model and
tested how this discharge rule varied by dual-eligibility status. SUBJECTS: A
total of 692,875 Medicare fee-for-service patients (22% duals) who were
discharged for Medicare paid SNF care between July 2004 and June 2005. MEASURES:
Medicare enrollment and the Medicaid Analytic Extract files were used to
determine dual eligibility. The proportion of Medicaid patients and nursing staff
characteristics provided measures of SNF quality. RESULTS: Duals are more likely
to be discharged to SNFs with a higher share of Medicaid patients and fewer
nurses. These results are robust to estimation with an alternative subsample of
patients based on primary diagnoses, propensity of being dual eligible, and
likelihood of remaining in the nursing home. CONCLUSIONS: Disparities exist in
access to quality SNF care for duals. Strategies to improve discharge planning
processes are required to redirect patients to higher quality providers,
regardless of Medicaid eligibility.
PMID- 24354696
TI - Merremoside D: de novo synthesis of the purported structure, NMR analysis, and
comparison of spectral data.
AB - The first synthesis of the purported structure of Merremoside D has been achieved
in 22 longest linear steps. The de novo asymmetric synthesis relied on the use of
asymmetric catalysis to selectively install all 21 stereocenters in the final
compounds from commercially available achiral starting materials. Adiabatic
gradient 2D NMR techniques (gHSQCAD, gHMBCAD, gH2BCAD, gHSQCTOXYAD, ROESYAD) were
used to completely assign the structure of synthetic Merremoside D. Comparison of
our assignments with the limited NMR data reported for natural Merremoside D
allows for the tentative confirmation of its structure.
PMID- 24354697
TI - Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by
the use of clot waveform analysis.
AB - BACKGROUND: Assays to determine the optimal hemostatic effects of bypass therapy
in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot
waveform analysis (CWA), based on the continuous monitoring of routine
coagulation parameters (prothrombin time/activated partial thromboplastin time),
offers a useful method for assessing global clotting function. OBJECTIVES: To
investigate the technique of CWA for the hemostatic monitoring of bypass therapy
in HA patients with inhibitors. METHODS AND RESULTS: Ellagic acid (Elg), tissue
factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard
parameters - clot time (CT), maximum coagulation velocity (|min1|), and
acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a
significant difference in these parameters between plasma from HA patients with
inhibitors and normal plasmas; and (ii) a significant improvement in these
indices in HA patients with inhibitors after bypass therapy. Experiments in vitro
demonstrated that there were significant differences between plasma from HA
patients with inhibitors and normal plasma with various triggers, in the order
Elg > Elg/TF >> TF. Addition of therapeutically achievable concentrations of
bypassing agents, however, showed significant improvements in the different
parameters only with Elg/TF, suggesting that this reagent provided the most
appropriate assay. A total of 20 plasmas from HA patients with inhibitors in
which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The
postinfusion parameters CT and |min2| reflected clinical effects, and were close
to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of
perioperative hemostatic management of bypass therapy in HA patients with
inhibitors. CONCLUSIONS: CWA is a promising method for the quantitative
monitoring of bypass therapy during routine automated clotting assays with a
modified trigger reagent comprising a well-balanced mixture of Elg and TF.
PMID- 24354699
TI - Analysis of legal claims--informing litigation systems and quality improvement.
PMID- 24354700
TI - Shoulder dystocia and Erb's palsy: is the accoucheur always guilty of negligence?
PMID- 24354701
TI - Author's reply: Ultrasound-guided transcervical forceps extraction of unruptured
interstitial pregnancy.
PMID- 24354702
TI - Ultrasound-guided transcervical forceps extraction of unruptured interstitial
pregnancy.
PMID- 24354703
TI - A report from #BlueJC: 'Mesh or no mesh' for pelvic organ prolapse?
PMID- 24354704
TI - BJOG editor's choice.
PMID- 24354706
TI - The Perceptions of Coronary heart disease Scale: psychometric validation using
confirmatory factor analysis.
PMID- 24354705
TI - Incidence of chronic bronchitis in a cohort of pulp mill workers with repeated
gassings to sulphur dioxide and other irritant gases.
AB - BACKGROUND: Occupational exposure to irritants is associated with chronic
bronchitis. The aim of this study was to elucidate whether repeated peak
exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other
irritant gases could increase the risk of chronic bronchitis. METHODS: The study
population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort
study, who completed a comprehensive questionnaire with items on chronic
bronchitis symptoms, smoking habit, occupational history, and specific exposures,
including gassings. 2,037 have worked in sulphite mills. Incidence rates and
hazard ratios (HRs) for the observation period, 1970-2000, in relation to
exposure and the frequency of repeated gassings to SO2 and other irritant gases
were calculated. RESULTS: The incidence rate for chronic bronchitis among workers
with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person
years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The
risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0
5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS:
Repeated gassings to irritant gases increased the incidence of chronic bronchitis
in our study population during and after work in pulp mills, supporting the
hypothesis that occupational exposures to irritants negatively affect the
airways. These results underscore the importance of preventive actions in this
work environment.
PMID- 24354707
TI - Does exercise induce hypoalgesia through conditioned pain modulation?
AB - Pain sensitivity decreases with exercise. The mechanisms that underlie this
exercise-induced hypoalgesia (EIH) are unclear. Our purpose was to investigate
conditioned pain modulation (CPM) as a potential mechanism of EIH. Sixteen women
completed pain testing during three sessions: painful exercise, nonpainful
exercise, and quiet rest. Intensity and unpleasantness ratings to noxious heat
stimuli were assessed at baseline and during and following each session. Results
showed that pain sensitivity decreased significantly during both exercise
sessions (p < .05), but not during quiet rest. Effect size calculations showed
that the size of the hypoalgesic response was greater following painful exercise
than nonpainful exercise. Our results suggest that exercise-induced muscle pain
may contribute to the magnitude of EIH. However, as pain sensitivity also
decreased following nonpainful exercise, CPM is not likely the primary mechanism
of EIH.
PMID- 24354708
TI - Atopic dermatitis presenting as generalized poikiloderma with filaggrin gene
mutation.
PMID- 24354709
TI - Stereoselective synthesis of the trisaccharide moiety of ganglioside HLG-2.
AB - The glycan portion of ganglioside HLG-2, which was identified in the extracts of
the sea cucumber Holothuria leucospilota , was synthesized in a highly efficient
and stereoselective manner. The unusual sequence of the trisaccharide moiety,
alpha-N-glycolylsialyl-(2,4)-alpha-N-acetylsialyl-(2,6)-glucoside, was assembled
by stereoselective coupling of a 5-N,4-O-carbonyl-protected sialyl phosphate
donor, a N-2,2,2-trichloroethoxycarbonyl (Troc)-protected sialyl acceptor, and a
(trimethylsilyl)ethyl-beta-glucosyl acceptor in high yield. The synthesis
featured the high-yielding construction of two alpha-sialyl linkages.
PMID- 24354710
TI - Exploring perinatal shift-to-shift handover communication and process: an
observational study.
AB - RATIONALE, AIMS AND OBJECTIVES: Loss of situation awareness (SA) by health
professionals during handover is a major threat to patient safety in perinatal
care. SA refers to knowing what is going on around. Adequate handover
communication and process may support situation assessment, a precursor of SA.
This study describes current practices and opinions of perinatal handover to
identify potential improvements. METHODS: Structured direct observations of shift
to-shift patient handovers (n = 70) in an academic perinatal setting were used to
measure handover communication (presence and order of levels of SA: current
situation, background, assessment and recommendation) and process (duration,
interruptions/distractions, eye contact, active inquiry and reading information
back). Afterwards, receivers' opinions of handover communication (n = 51) were
measured by means of a questionnaire. RESULTS: All levels of SA were present in
7% of handovers, the current situation in 86%, the background in 99%, an
assessment in 24% and a recommendation in 46%. In 77% of handovers the background
was mentioned first, followed by the current situation. Forty-four per cent of
handovers took 2 minutes or more per patient. In 52% distractions occurred, in
43% there was no active inquiry, in 32% no eye contact and in 97% information was
not read back. The overall mean of the receivers' opinions of handover
communication was 4.1 (standard deviation +/- 0.7; scale 1-5, where 5 is
excellent). CONCLUSIONS: Perinatal handovers are currently at risk for inadequate
situation assessment because of variability and limitations in handover
communication and process. However, receivers' opinions of handover communication
were very positive, indicating a lack of awareness of patient safety threats
during handover. Therefore, the staff's awareness of current limitations should
be raised, for example through video reflection or simulation training.
PMID- 24354711
TI - Comparison of intense pulsed light with 1,927-nm fractionated thulium fiber laser
for the rejuvenation of the chest.
AB - BACKGROUND: Rejuvenation of the aging chest is important to prevent noticeable
disparities between the treated skin of the face and that of the untreated chest.
OBJECTIVE: To compare a high-density thulium fiber laser (TFL)-based protocol for
the rejuvenation of the aging chest with intense pulsed light (IPL). METHODS AND
MATERIALS: We conducted a retrospective chart review comparing patients treated
with IPL and those treated with TFL in combination with a quality-switched
alexandrite laser and long pulsed dye laser. Blinded photographic assessment of
overall improvement, rhytides, skin texture, dyspigmentation, and telangiectasia
was performed. Patient satisfaction was assessed in a standardized follow-up
survey. Cost and practicality were compared. RESULTS: At a mean follow-up of 45.8
days for IPL and 78.3 days for TFL, the two protocols had comparable clinical
efficacy in achieving rejuvenation of the chest. Differences existed in terms of
cost and practicality. CONCLUSION: TFL can be used at high density and in
simultaneous combination with other targeted laser modalities to achieve
rejuvenation of the aging chest. IPL achieves similar clinical efficacy. The
choice between treatment modalities depends on physician and patient preferences.
PMID- 24354712
TI - A systematic review of health service interventions to improve linkage with or
retention in HIV care.
AB - The importance of early linkage to and continuing retention in HIV care is
increasingly recognised, particularly in light of the implications poor linkage
and retention rates have for the effectiveness of HIV treatment as prevention
strategies. The purpose of this systematic review was to examine the
effectiveness of healthcare interventions in improving patient linkage to or
retention in HIV care. We systematically searched PubMed (MEDLINE and PubMed-only
citations) and EMBASE databases for articles reporting the original results of
randomised controlled trials, and used a standard data collection form to extract
information on study characteristics and outcome data. Five articles met the
inclusion criteria, of which two articles focused on linkage to care and three on
retention in care. The methodological quality, both of internal and external
validity, of most of the trials was suboptimal. Wide variation in the
interventions and outcome measures meant synthesis of the results using meta
analysis was not appropriate. This review shows evidence that interventions based
on supporting patient self-management improves linkage to, and possibly retention
in, care. Interventions aimed at delivery service design may also be effective,
although evidence in this review was limited. It is vital that interventions are
developed to improve patient engagement in HIV care. The dearth of research
identified by this review highlights the need for well-designed trials of
interventions in this area in the future.
PMID- 24354713
TI - Regional environmental pressure influences population differentiation in turbot
(Scophthalmus maximus).
AB - Unravelling the factors shaping the genetic structure of mobile marine species is
challenging due to the high potential for gene flow. However, genetic inference
can be greatly enhanced by increasing the genomic, geographical or environmental
resolution of population genetic studies. Here, we investigated the population
structure of turbot (Scophthalmus maximus) by screening 17 random and gene-linked
markers in 999 individuals at 290 geographical locations throughout the northeast
Atlantic Ocean. A seascape genetics approach with the inclusion of high
resolution oceanographical data was used to quantify the association of genetic
variation with spatial, temporal and environmental parameters. Neutral loci
identified three subgroups: an Atlantic group, a Baltic Sea group and one on the
Irish Shelf. The inclusion of loci putatively under selection suggested an
additional break in the North Sea, subdividing southern from northern Atlantic
individuals. Environmental and spatial seascape variables correlated marginally
with neutral genetic variation, but explained significant proportions
(respectively, 8.7% and 10.3%) of adaptive genetic variation. Environmental
variables associated with outlier allele frequencies included salinity,
temperature, bottom shear stress, dissolved oxygen concentration and depth of the
pycnocline. Furthermore, levels of explained adaptive genetic variation differed
markedly between basins (3% vs. 12% in the North and Baltic Sea, respectively).
We suggest that stable environmental selection pressure contributes to relatively
strong local adaptation in the Baltic Sea. Our seascape genetic approach using a
large number of sampling locations and associated oceanographical data proved
useful for the identification of population units as the basis of management
decisions.
PMID- 24354715
TI - Comparing different sterol containing solid lipid nanoparticles for targeted
delivery of quercetin in hepatocellular carcinoma.
AB - Quercetin (QT) is a potential chemotherapeutic drug with low solubility that
seriously limits its clinical use. The aim of this study was enhancing cellular
penetration of QT by sterol containing solid lipid nanoparticles (SLNs) which
make bilayers fluent for targeting hepatocellular carcinoma cells. Three
variables including sterol type (cholesterol, stigmasterol and stigmastanol),
drug and sterol content were studied in a surface response D-optimal design for
preparation of QT-SLNs by emulsification solvent evaporation method. The studied
responses included particle size, zeta potential, drug loading capacity and 24 h
release efficiency (RE24%). Scanning electron and atomic force microscopy were
used to study the morphology of QT-SLNs and their thermal behavior was studied by
DSC analysis. Cytotoxicity of QT-SLNs was determined by MTT assay on HepG-2 cells
and cellular uptake by fluorescence microscopy method. Optimized QT-SLNs obtained
from cholesterol and QT with the ratio of 2:1 that showed particle size of 78.0
+/- 7.0 nm, zeta potential of -22.7 +/- 1.3 mV, drug loading efficiency of 99.9
+/- 0.5% and RE24 of 56.3 +/- 3.4%. IC50 of QT in cholesterol SLNs was about six
and two times less than free QT and phytosterol SLNs, respectively, and caused
more accumulation of QT in HepG2 cells. Blank phytosterol SLNs were toxic on
cells.
PMID- 24354714
TI - Intralesional cryotherapy versus excision and corticosteroids or brachytherapy
for keloid treatment: study protocol for a randomised controlled trial.
AB - BACKGROUND: Keloids are a burden for patients due to physical, aesthetic and
social complaints and treatment remains a challenge because of therapy resistance
and high recurrence rates. The main goal of treatment is to improve the quality
of life (QoL); this implies that, apart from surgical outcomes, patient-reported
outcome measures (PROMs) need to be taken into account. Decision making in keloid
treatment is difficult due to heterogeneity of the condition and the lack of
comparative studies. METHODS/DESIGN: This is a multicentre, randomised controlled
open trial that compares 1) intralesional cryotherapy versus excision and
corticosteroids for primary keloids, and 2) intralesional cryotherapy versus
excision and brachytherapy for therapy-resistant keloids. The primary outcome is
the Patient and Observer Scar Assessment Scale (POSAS), a 12-item scale (with
score 12 indicating the best and 120 indicating the worst scar imaginable). A
difference of six points on the total score is considered to be of clinical
importance. Secondary outcomes are recurrence rates, volume reduction, Skindex-29
scores, SF-36 scores and complication rates. Primary and secondary outcome
measurements are taken at baseline, and at 2, 12, 26 and 52 weeks
postoperatively. For analysis, a linear mixed model is used. A total of 176
patients will be included over a period of 2.5 years. The protocol is approved by
the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam
and follows good clinical practice guidelines. DISCUSSION: The outcomes of this
study will improve evidence-based decision making for the treatment of keloids,
as well as patient education. TRIAL REGISTRATION: Dutch Trial Register NTR4151.
PMID- 24354716
TI - Walking on ballast impacts balance.
AB - Railroad workers often perform daily work activities on irregular surfaces,
specifically on ballast rock. Previous research and injury epidemiology have
suggested a relationship between working on irregular surfaces and postural
instability. The purpose of this study was to examine the impact of walking on
ballast for an extended duration on standing balance. A total of 16 healthy adult
males walked on a 7.62 m * 4.57 m (25 ft * 15 ft) walking surface of no ballast
(NB) or covered with ballast (B) of an average rock size of about 1 inch for 4 h.
Balance was evaluated using dynamic posturography with the NeuroCom((r)) Equitest
System(TM) prior to experiencing the NB or B surface and again every 30 min
during the 4 h of ballast exposure. Dependent variables were the sway velocity
and root-mean-square (RMS) sway components in the medial-lateral and anterior
posterior directions. Repeated measures ANOVA revealed statistically significant
differences in RMS and sway velocity between ballast surface conditions and
across exposure times. Overall, the ballast surface condition induced greater
sway in all of the dynamic posturography conditions. Walking on irregular
surfaces for extended durations has a deleterious effect on balance compared to
walking on a surface without ballast. These findings of changes in balance during
ballast exposure suggest that working on an irregular surface may impact postural
control.
PMID- 24354717
TI - The Nordic long-term OCD treatment study (NordLOTS): rationale, design, and
methods.
AB - BACKGROUND: This paper describes and discusses the methodology of the Nordic long
term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was
to study treatment outcome of CBT, to identify CBT non- or partial responders and
to investigate whether an increased number of CBT-sessions or sertraline
treatment gives the best outcome; to identify treatment refractory patients and
to investigate the outcome of aripiprazole augmentation; to study the outcome
over a three year period for each responder including the risk of relapse, and
finally to study predictors, moderators and mediators of treatment response.
METHODS: Step 1 was an open and uncontrolled clinical trial with CBT, step 2 was
a controlled, randomised non-blinded study of CBT non-responders from step 1.
Patients were randomized to receive either sertraline plus CBT-support or
continued and modified CBT. In step 3 patients who did not respond to either CBT
or sertraline were treated with aripiprazole augmentation to sertraline.
CONCLUSIONS: This multicenter trial covering three Scandinavian countries is
going to be the largest CBT-study for paediatric OCD to date. It is not funded by
industry and tries in the short and long-term to answer the question whether
further CBT or SSRI is better in CBT non-responders.
PMID- 24354718
TI - Characteristics and performance of minority-serving dialysis facilities.
AB - OBJECTIVE: To examine the structure, processes, and outcomes of American dialysis
facilities that predominantly treat racial-ethnic minority patients. DATA
SOURCES/STUDY SETTING: Secondary analysis of data from all patients who initiated
dialysis during 2005-2008 in the United States. STUDY DESIGN: In this
retrospective cohort study, we examined the associations of the racial-ethnic
composition of the dialysis facility with facility-level survival and achievement
of performance targets for anemia and dialysis adequacy. DATA
COLLECTION/EXTRACTION METHODS: We obtained dialysis facility- and patient-level
data from the national data registry of patients with end-stage renal disease. We
linked these data with clinical performance measures from the Centers for
Medicare and Medicaid Services. PRINCIPAL FINDINGS: Overall, minority-serving
facilities were markedly larger, more often community based, and less likely to
offer home dialysis than facilities serving predominantly white patients. A
significantly higher proportion of minority-serving dialysis facilities exhibited
worse than expected survival as compared with facilities serving predominantly
white patients (p < .001 for each). However, clinical performance measures for
anemia and dialysis adequacy were similar across minority-serving status.
CONCLUSIONS: While minority-serving facilities generally met dialysis performance
targets mandated by Medicare, they exhibited worse than expected patient
survival.
PMID- 24354719
TI - Intestinal dysbacteriosis contributes to decreased intestinal mucosal barrier
function and increased bacterial translocation.
AB - The purpose of this study was to determine the effect of colistin-induced
intestinal dysbacteriosis on intestinal mucosal barrier function and bacterial
translocation in a mouse model. Colistin or saline was administered orally for 7
days, and populations of viable organisms from the caecal mucosa and its content,
the ileal segments, the mesenteric lymph nodes (MLNs) and the internal organs
were prepared for examination. In the intestinal dysbacteriosis model, intestinal
barrier dysfunction was observed and associated with increased bacterial
translocation to extraintestinal sites. The extent of bacterial translocation to
the MLNs and internal organs in the colistin group was significantly higher than
in the saline group. Colistin-induced intestinal dysbacteriosis was shown to
injure the intestinal mucosa barrier function and increase bacterial dislocation.
SIGNIFICANCE AND IMPACT OF THE STUDY: Colistin has been reported to be effective
in selective digestive decontamination (SDD), which is an infection prevention
measure used in the treatment of certain patients in intensive care. We are the
first to report that colistin-induced intestinal dysbacteriosis can injure
intestinal mucosal barrier function and increase bacterial translocation, whereas
a high dose of colistin does not damage the intestinal mucosal barrier in germ
free (GF) mice raised in a GF environment. These results may indicate that
prolonged use of a high dose of a SDD medication should be carefully considered.
PMID- 24354720
TI - Emotional responses to honour situations in Turkey and the northern USA.
AB - The main goal of the current research is to investigate emotional reactions to
situations that implicate honour in Turkish and northern American cultural
groups. In Studies 1A and 1B, participants rated the degree to which a variety of
events fit their prototypes for honour-related situations. Both Turkish and
American participants evaluated situations generated by their co-nationals as
most central to their prototypes of honour-related situations. Study 2 examined
emotional responses to Turkish or US-generated situations that varied in
centrality to the prototype. Highly central situations and Turkish-generated
situations elicited stronger emotions than less central situations and US
generated situations. Americans reported higher levels of positive emotions in
response to honour-enhancing situations than did Turkish participants. These
findings demonstrate that the prototypes of honour relevant situations differ for
Turkish and northern American people, and that Turkish honour relevant situations
are more emotion-laden than are northern American honour relevant situations.
PMID- 24354721
TI - Environmental enrichment and brain repair: harnessing the therapeutic effects of
cognitive stimulation and physical activity to enhance experience-dependent
plasticity.
AB - Environmental enrichment (EE) increases levels of novelty and complexity,
inducing enhanced sensory, cognitive and motor stimulation. In wild-type rodents,
EE has been found to have a range of effects, such as enhancing experience
dependent cellular plasticity and cognitive performance, relative to standard
housed controls. Whilst environmental enrichment is of course a relative term,
dependent on the nature of control environmental conditions, epidemiological
studies suggest that EE has direct clinical relevance to a range of neurological
and psychiatric disorders. EE has been demonstrated to induce beneficial effects
in animal models of a wide variety of brain disorders. The first evidence of
beneficial effects of EE in a genetically targeted animal model was generated
using Huntington's disease transgenic mice. Subsequent studies found that EE was
also therapeutic in mouse models of Alzheimer's disease, consistent with
epidemiological studies of relevant environmental modifiers. EE has also been
found to ameliorate behavioural, cellular and molecular deficits in animal models
of various neurological and psychiatric disorders, including Parkinson's disease,
stroke, traumatic brain injury, epilepsy, multiple sclerosis, depression,
schizophrenia and autism spectrum disorders. This review will focus on the
effects of EE observed in animal models of neurodegenerative brain diseases, at
molecular, cellular and behavioural levels. The proposal that EE may act
synergistically with other approaches, such as drug and cell therapies, to
facilitate brain repair will be discussed. I will also discuss the therapeutic
potential of 'enviromimetics', drugs which mimic or enhance the therapeutic
effects of cognitive activity and physical exercise, for both neuroprotection and
brain repair.
PMID- 24354722
TI - Nucleic acids--chemistry and applications.
PMID- 24354723
TI - Patients with single ventricle anatomy may respond better to octreotide therapy
for chylothorax after congenital heart surgery.
AB - BACKGROUND AND AIMS: Chylothorax (CTX) occurs in 3% to 6% of children after
surgery for congenital heart disease with significant morbidity and mortality.
Octreotide has been proposed as therapy, but there are no predictors of response.
The objective of this study was to identify possible predictors of response to
octreotide. METHODS: Single-center retrospective review of patients who developed
CTX after cardiac surgery. Data collected included demographics, cardiac lesion,
surgical data, hospital course, CTX volume and duration, and interventions for
CTX. Patients who received octreotide as part of their therapy were compared to
those who did not. RESULTS: A total of 1150 patients underwent 1455 cardiac
surgeries with 67 (4.6%) episodes of CTX. Patients with CTX were younger, lower
weight, more likely to undergo cardiopulmonary bypass, and had higher RACHS-1
scores and mortality. Nineteen patients with CTX received octreotide as part of
their treatment and six (32%) had at least 50% reduction in CTX volume. Patients
who responded to octreotide had lower CTX volume (18 mL/kg/day vs. 55 mL/kg/day,
p=0.023) and a higher proportion of patients with single ventricle anatomy (67%
vs. 18%, p=0.046). CONCLUSIONS: There is a subset of patients who seem to respond
to octreotide, but they have lower CTX volume and may have already been improving
before octreotide therapy. Patients with single ventricle anatomy seemed to
respond to octreotide and may benefit from its use.
PMID- 24354724
TI - Cerebral maturation on amplitude-integrated electroencephalography and perinatal
exposures in preterm infants.
AB - AIM: To determine the associations between perinatal exposures, cerebral
maturation on amplitude-integrated encephalography (aEEG) and outcome. METHODS:
During this prospective cohort study, 136 infants <=30 weeks estimated
gestational age received 4 h of aEEG at four time points (between the first 2
weeks of life and term-equivalent age) during hospitalisation. Perinatal factors
were documented. Associations between perinatal exposures and Burdjalov-scores
were investigated. Neurodevelopmental outcome was assessed at the age of two.
RESULTS: Immature cyclicity on the initial aEEG recording was associated with
higher CRIB score (p = 0.01), vaginal delivery (p = 0.02), male gender (p < 0.01)
and death (p = 0.01). Perinatal factors associated with lower Burdjalov-scores
included cerebral injury (p < 0.01), sepsis (p < 0.01), lower caffeine dose (p =
0.006), prolonged mechanical ventilation (p = 0.002) and death (p < 0.01).
Burdjalov-scores at 30 (beta = 2.62, p < 0.01) and 34 weeks postmenstrual age
(beta = 2.89, p = 0.05) predicted motor scores. CONCLUSION: aEEG measures of
cyclicity and Burdjalov-scores in the first 6 weeks of life, with an emphasis on
30 and 34 weeks postmenstrual age, demonstrated associations with perinatal
factors known to predict adverse neurodevelopmental outcome.
PMID- 24354725
TI - Design of a rotamer library for coarse-grained models in protein-folding
simulations.
AB - Rotamer libraries usually contain geometric information to trace an amino acid
side chain, atom by atom, onto a protein backbone. These libraries have been
widely used in protein design, structure refinement and prediction, homology
modeling, and X-ray and NMR structure validation. However, they usually present
too much information and are not always fully compatible with the coarse-grained
models of the protein geometry that are frequently used to tackle the protein
folding problem through molecular simulation. In this work, we introduce a new
backbone-dependent rotamer library for side chains compatible with low-resolution
models in polypeptide chains. We have dispensed with an atomic description of
proteins, representing each amino acid side chain by its geometric center (or
centroid). The resulting rotamers have been estimated from a statistical analysis
of a large structural database consisting of high-resolution X-ray protein
structures. As additional information, each rotamer includes the frequency with
which it has been found during the statistical analysis. More importantly, the
library has been designed with a careful control to ensure that the vast majority
of side chains in protein structures (at least 95% of residues) are properly
represented. We have tested our library using an independent set of proteins, and
our results support a good correlation between the reconstructed centroids from
our rotamer library and those in the experimental structures. This new library
can serve to improve the definition of side chain centroids in coarse-grained
models, avoiding at the same time an excessive additional complexity in a
geometric model for the polypeptide chain.
PMID- 24354726
TI - The availability of HEPA-filtered rooms and the incidence of pneumonia in
patients after haematopoietic stem cell transplantation (HSCT): results from a
prospective, multicentre, eastern European study.
AB - AIMS AND OBJECTIVES: To establish the availability of High Efficiency Particulate
Air (HEPA)- and nonHEPA-filtered rooms in eastern European transplant centres and
to investigate the impact on incidence of pneumonia and mortality after
haematopoietic stem cell transplantation (HSCT). BACKGROUND: Barrier nursing in
HEPA-filtered rooms is generally recommended for patients undergoing HSCT. There
are only limited data on the availability of HEPA-filtered rooms and the impact
on incidence of pneumonia and mortality. DESIGN: A prospective, observational,
international study. METHODS: Monitoring cards were distributed within the East
Forum EBMT-Nurses Group cooperating centres, and 689 consecutive patients were
registered in 1/2010-6/2012. Patients were monitored for 100 days post
transplant. RESULTS: In patients undergoing autologous HSCT, pneumonia developed
in 14/400 (3.5%) and was the cause of death in 2/14 (14%) of patients. There was
no significant difference in mortality between HEPA-filtered and nonHEPA-filtered
groups (4.5% vs. 4.9%, respectively). 239/400 (59%) transplantations were
performed in single-bed rooms [190/239 (79%) HEPA-filtered] and 161 (41%) in two
bed rooms [28/161 (17%) HEPA-filtered]. In allogeneic transplantation, pneumonia
developed in 24/289 (8.3%) and was the cause of death in 11/24 (45%) of patients.
There was no significant difference in mortality between HEPA-filtered and non
HEPA-filtered groups (14% vs. 17%, respectively). 281/289 (97%) of allogeneic
transplantations were performed in single-bed rooms [254/281 (90%) HEPA
filtered], and pneumonia was more frequent in patients on corticosteroids and in
rooms without HEPA. CONCLUSION: The incidence of pneumonia in the autologous
transplantation setting is low. More pneumonia was observed in the allogeneic
HSCT group, especially in patients on corticosteroids. There was a trend towards
a lower incidence of pneumonia in allogeneic HSCT patients treated in HEPA
filtered rooms. RELEVANCE TO CLINICAL PRACTICE: Autologous HSCT transplantation
may safely be performed without HEPA filtration. HEPA filtration might be
preferable in patients undergoing allogeneic transplantation.
PMID- 24354727
TI - Validation of the Polish version of the EORTC QLQ-OV28 module for the assessment
of health-related quality of life in women with ovarian cancer.
AB - The aim of our study was to undertake a prospective validation study of the
Polish version of the EORTC ovarian cancer (EORTC QLQ-OV28) module used together
with the EORTC QLQ-C30. The translated module was pilot-tested according to the
EORTC guidelines. Patients with histological confirmation of ovarian cancer were
eligible for the study. All patients filled out the Polish version of the EORTC
QLQ-OV28, the EORTC QLQ-C30 and a demographic questionnaire. Standard validity
and reliability analyses were performed. One-hundred and forty patients agreed to
take part in the study (mean age +/- standard deviation: 63.3 +/- 10.2 years).
Cronbach's alpha coefficients showed positive internal consistency (0.78-0.91).
Interclass correlations for the EORTC QLQ-OV28 ranged from 0.77 to 0.93 and
proved appropriate test-retest reliability. Satisfactory convergent and
discriminant validity in multi-trait scaling analyses was seen. The Polish
version of the EORTC QLQ-OV28 module proved to be a reliable and valid tool for
measuring health-related quality of life in patients with ovarian cancer.
PMID- 24354728
TI - The partial thromboplastin time: reply.
PMID- 24354729
TI - Diagnostic gene expression biomarkers of coral thermal stress.
AB - Gene expression biomarkers can enable rapid assessment of physiological
conditions in situ, providing a valuable tool for reef managers interested in
linking organism physiology with large-scale climatic conditions. Here, we
assessed the ability of quantitative PCR (qPCR)-based gene expression biomarkers
to evaluate (i) the immediate cellular stress response (CSR) of Porites
astreoides to incremental thermal stress and (ii) the magnitude of CSR and
cellular homeostasis response (CHR) during a natural bleaching event. Expression
levels largely scaled with treatment temperature, with the strongest responses
occurring in heat-shock proteins. This is the first demonstration of a 'tiered'
CSR in a coral, where the magnitude of expression change is proportional to
stress intensity. Analysis of a natural bleaching event revealed no signature of
an acute CSR in normal or bleached corals, indicating that the bleaching
stressor(s) had abated by the day of sampling. Another long-term stress CHR-based
indicator assay was significantly elevated in bleached corals, although assay
values overall were low, suggesting good prospects for recovery. This study
represents the first step in linking variation in gene expression biomarkers to
stress tolerance and bleaching thresholds in situ by quantifying the severity of
ongoing thermal stress and its accumulated long-term impacts.
PMID- 24354730
TI - Knowledge, understanding, and use of preventive strategies against nonmelanoma
skin cancer in healthy and immunosuppressed individuals undergoing Mohs surgery.
AB - BACKGROUND: Despite various national recommendations advising individuals to
reduce their exposure to ultraviolet radiation, many people still do not use
these skin cancer prevention strategies. OBJECTIVES: To assess patient sources of
medical information, knowledge of sun protection strategies, and barriers to
implementing these strategies and to compare the overall rate of use of skin
cancer prevention strategies of healthy and immunocompromised patients. MATERIALS
AND METHODS: Survey-based study conducted on 140 individuals undergoing Mohs
surgery. RESULTS: Seventy-three percent of healthy and 74% of immunosuppressed
participants identified sunscreen use as a form of protective strategy, whereas
36% and 27%, respectively, used sunscreen daily. Participants cited physicians
and the internet as equal sources of medical information. Knowing two or more
strategies correlated to a higher self-rating of daily use of any protective
strategy. CONCLUSION: General knowledge regarding sun protection strategies is
limited, but awareness of multiple strategies correlated with greater sun
protective behavior. Despite having a much higher incidence of skin cancers, the
immunosuppressed group did not show more awareness of prevention strategies or
higher use than healthy participants.
PMID- 24354731
TI - What's normal? Influencing women's perceptions of normal genitalia: an experiment
involving exposure to modified and nonmodified images.
AB - OBJECTIVE: Examine women's perceptions of what is 'normal' and 'desirable' in
female genital appearance. DESIGN: Experiment with random allocation across three
conditions. SETTING: Community. SAMPLE: A total of 97 women aged 18-30 years.
METHODS: Women were randomly assigned to view a series of images of (1)
surgically modified vulvas or (2) nonmodified vulvas, or (3) no images. They then
viewed and rated ten target images of surgically modified vulvas and ten of
unmodified vulvas. MAIN OUTCOME MEASURES: Women used a four-point Likert scale
('strongly agree' to 'strongly disagree'), to rate each target image for 'looks
normal' and 'represents society's ideal'. For each woman, we created two summary
scores that represented the extent to which she rated the unmodified vulvas as
more 'normal' and more 'society's ideal' than the modified vulvas. RESULTS: For
ratings of 'normality,' there was a significant effect for condition (F2,94 =
2.75 P = 0.007, radj2 = 0.082): women who had first viewed the modified images
rated the modified target vulvas as more normal than the nonmodified vulvas,
significantly different from the control group, who rated them as less normal.
For ratings of 'society's ideal', there was again a significant effect for
condition (F2,92 = 7.72, P < 0.001, radj2 = 0.125); all three groups rated
modified target vulvas as more like society's ideal than the nonmodified target
vulvas, with the effect significantly strongest for the women who had viewed the
modified images. CONCLUSIONS: Exposure to images of modified vulvas may change
women's perceptions of what is normal and desirable. This may explain why some
healthy women seek labiaplasty.
PMID- 24354732
TI - Speaking under pressure: low linguistic complexity is linked to high
physiological and emotional stress reactivity.
AB - What can a speech reveal about someone's state? We tested the idea that greater
stress reactivity would relate to lower linguistic cognitive complexity while
speaking. In Study 1, we tested whether heart rate and emotional stress
reactivity to a stressful discussion would relate to lower linguistic complexity.
In Studies 2 and 3, we tested whether a greater cortisol response to a
standardized stressful task including a speech (Trier Social Stress Test) would
be linked to speaking with less linguistic complexity during the task. We found
evidence that measures of stress responsivity (emotional and physiological) and
chronic stress are tied to variability in the cognitive complexity of speech.
Taken together, these results provide evidence that our individual experiences of
stress or "stress signatures"-how our body and mind react to stress both in the
moment and over the longer term-are linked to how complex our speech under
stress.
PMID- 24354734
TI - Nucleic acids--chemistry and applications.
PMID- 24354733
TI - A method to screen U.S. environmental biomonitoring data for race/ethnicity and
income-related disparity.
AB - BACKGROUND: Environmental biomonitoring data provide one way to examine
race/ethnicity and income-related exposure disparity and identify potential
environmental justice concerns. METHODS: We screened U.S. National Health and
Nutrition Examination Survey (NHANES) 2001-2008 biomonitoring data for 228
chemicals for race/ethnicity and income-related disparity. We defined six
subgroups by race/ethnicity-Mexican American, non-Hispanic black, non-Hispanic
white-and income-Low Income: poverty income ratio (PIR) <2, High Income: PIR >=
2. We assessed disparity by comparing the central tendency (geometric mean [GM])
of the biomonitoring concentrations of each subgroup to that of the reference
subgroup (non-Hispanic white/High Income), adjusting for multiple comparisons
using the Holm-Bonferroni procedure. RESULTS: There were sufficient data to
estimate at least one geometric mean ratio (GMR) for 108 chemicals; 37 had at
least one GMR statistically different from one. There was evidence of potential
environmental justice concern (GMR significantly >1) for 12 chemicals: cotinine;
antimony; lead; thallium; 2,4- and 2,5-dichlorophenol; p,p'
dichlorodiphenyldichloroethylene; methyl and propyl paraben; and mono-ethyl, mono
isobutyl, and mono-n-butyl phthalate. There was also evidence of GMR
significantly <1 for 25 chemicals (of which 17 were polychlorinated biphenyls).
CONCLUSIONS: Although many of our results were consistent with the U.S.
literature, findings relevant to environmental justice were novel for
dichlorophenols and some metals.
PMID- 24354735
TI - Advances in understanding stroke risk in children--a geneticist's view.
AB - The advent of the genomic era has provided novel insights into the genetic
architecture of common complex diseases, such as thrombophilia and stroke. Since
2006, a growing number of genome wide association studies (GWAS) for common
complex diseases have revealed new candidate loci and genomic regions that play
an important role in disease aetiology and progression. While GWAS on the above
mentioned traits are abundant in adults, similar studies in paediatric study
cohorts are lagging behind. However, genetic research in this important clinical
area has gained momentum and starts to provide us with exciting insights into the
genetic underpinnings of stroke with paediatric onset. Here we review recent
advances in genetic association studies underlying stroke in children and aim to
translate the results to clinical utility. These studies comprise candidate gene
approaches and GWAS, and represent the current status on what we have learnt
about the genetic architecture underlying paediatric stroke, and how this may
affect medical practice in the years to come.
PMID- 24354737
TI - Inferring the contribution of sexual reproduction, migration and off-season
survival to the temporal maintenance of microbial populations: a case study on
the wheat fungal pathogen Puccinia striiformis f.sp. tritici.
AB - Understanding the mode of temporal maintenance of plant pathogens is an important
domain of microbial ecology research. Due to the inconspicuous nature of
microbes, their temporal maintenance cannot be studied directly through tracking
individuals and their progeny. Here, we suggest a series of population genetic
analyses on molecular marker variation in temporally spaced samples to infer
about the relative contribution of sexual reproduction, off-season survival and
migration to the temporal maintenance of pathogen populations. We used the
proposed approach to investigate the temporal maintenance of wheat yellow rust
pathogen, Puccinia striiformis f.sp. tritici (PST), in the Himalayan region of
Pakistan. Multilocus microsatellite genotyping of PST isolates revealed high
genotypic diversity and recombinant population structure across all locations,
confirming the existence of sexual reproduction in this region. The genotypes
were assigned to four genetic groups, revealing a clear differentiation between
zones with and without Berberis spp., the alternate host of PST, with an
additional subdivision within the Berberis zone. The lack of any differentiation
between samples across two sampling years, and the very infrequent resampling of
multilocus genotypes over years at a given location was consistent with limited
over-year clonal survival, and a limited genetic drift. The off-season
oversummering population in the Berberis zone, likely to be maintained locally,
served as a source of migrants contributing to the temporal maintenance in the
non-Berberis zone. Our study hence demonstrated the contribution of both sexual
recombination and off-season oversummering survival to the temporal maintenance
of the pathogen. These new insights into the population biology of PST highlight
the general usefulness of the analytical approach proposed.
PMID- 24354736
TI - A new method for measuring the psychoacoustical properties of tinnitus.
AB - BACKGROUND: This study investigates the usefulness and effectiveness of a new way
of tinnitus screening and diagnosing. The authors believe that in order to arrive
at relevant diagnostic information, select the tinnitus treatment and
quantitatively substantiate its effects, the measurement of the Tinnitus
psychoacoustic parameters should be made an inherent part of the Tinnitus
therapy. METHODS: For this purpose the multimedia-based sound synthesizer has
been proposed for testing tinnitus and the results obtained this way are compared
with the outcome of the audiometer-based Wilcoxon test. The method has been
verified with 14 patients suffering from tinnitus. RESULTS: The experiments
reveal capabilities, limitations, advantages and disadvantages of both methods.
The synthesizer enables the patient to estimate his/her tinnitus more than twice
as fast as the audiometer and makes the information on the tinnitus character
perception more accurate. The analysis of the Wilcoxon test results shows that
there are statistically important differences between the two tests. CONCLUSIONS:
Patients using the synthesizer operate the software application themselves and
thus get more involved in testing. Moreover, they do not concentrate on
describing verbally their tinnitus, which could be difficult for some of them. As
a result, the test outcome is closer to the perceived tinnitus. However, the more
complex the description of the perceived tinnitus, the harder it is to determine
the sound parameters of the patient's perception. It also takes more time
regardless of the method. VIRTUAL SLIDES: The virtual slide(s) for this article
can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1954066324109436.
PMID- 24354738
TI - Effects of oral care solutions on mucous membrane integrity and bacterial
colonization.
AB - AIM: This research was conducted with the aim of determining the influence of
three different oral care solutions on oral mucous membrane integrity in
critically ill patients. BACKGROUND: Oral care is a basic part of nursing care in
intensive care units. DESIGN: A randomized controlled trial was conducted.
METHOD: A total of 60 patients (20 patients in each group) comprised the study
sample of the research. Patients were randomly allocated to three groups.
Patients in groups 1, 2 and 3 were administered mouth care three times a day
using 5% sodium bicarbonate, 0.2% chlorhexidine and saline solution,
respectively. Data were collected by means of a 'Descriptive characteristics
form' and an 'oral assessment tool'. RESULTS: Mean scores of oral assessment tool
increased according to days in all groups, however, this increase was found to be
statistically insignificant (p > 0.05). Mean scores of the patients in saline
solution group were seen to be lower than those of the other groups. When inter
group comparison of days was done, the difference between oral assessment scores
was found to be statistically significant (p = 0.000). CONCLUSION: It was found
that there was no difference between patient groups receiving saline solution,
sodium bicarbonate and 0.2% chlorhexidine for mouth care in terms of oral mucous
membrane integrity; oral mucosa of all patients was found to be mildly
dysfunctioning. RELEVANCE TO CLINICAL PRACTICE: It is thought that standardized
protocols for oral hygiene developed in the light of the findings of randomized
controlled trials may improve the oral health in critically ill patients.
PMID- 24354739
TI - Body maps on the human genome.
AB - BACKGROUND: Chromosomes have territories, or preferred locales, in the cell
nucleus. When these sites are taken into account, some large-scale structure of
the human genome emerges. RESULTS: The synoptic picture is that genes highly
expressed in particular topologically compact tissues are not randomly
distributed on the genome. Rather, such tissue-specific genes tend to map
somatotopically onto the complete chromosome set. They seem to form a "genome
homunculus": a multi-dimensional, genome-wide body representation extending
across chromosome territories of the entire spermcell nucleus. The antero
posterior axis of the body significantly corresponds to the head-tail axis of the
nucleus, and the dorso-ventral body axis to the central-peripheral nucleus axis.
CONCLUSIONS: This large-scale genomic structure includes thousands of genes. One
rationale for a homuncular genome structure would be to minimize connection costs
in genetic networks. Somatotopic maps in cerebral cortex have been reported for
over a century.
PMID- 24354740
TI - A theoretical framework for cognitive and non-cognitive interventions for older
adults: stimulation versus compensation.
AB - BACKGROUND: Recently, interest in cognitive training for older adults has grown
significantly, reflecting a need for preserving the quality of life into late
adulthood. In spite of increasing interest in cognitive rehabilitation, recent
meta-analyses have questioned reported training gains and determined that
cognitive gain from cognitive training might be no larger than the gain observed
from active controls such as unspecific, non-cognitive activities. AIMS: This
paper presents a theoretical framework for clarifying specificity of cognitive
training by exploring mechanisms of current cognitive and non-cognitive
interventions for older adults. By differentiating compensatory aspects from the
components of specific and non-specific stimulation in current training, two
related strategies of interventions for age-related cognitive decline, i.e.,
stimulation versus compensation, are proposed. OVERVIEW: Current interventions
for age-related cognitive decline are reviewed in terms of stimulation- and
compensation-focused interventions. Stimulation-focused, cognitive and non
cognitive training, with or without specific targets, tend to result in general
improvement in attention and sensory or other cognitive functions. Meanwhile,
compensation-focused training is likely to be the most effective when the
intervention specifically supports the frontally mediating activity in accordance
with the direction of indigenous adjustments in the aging brain. CONCLUSIONS: It
can be inferred that stimulation-focused training is to ameliorate the adverse
effects of neurological aging, whereas compensation-focused cognitive training is
primarily to facilitate compensatory adaptation in the brain.
PMID- 24354741
TI - The complete mitochondrial genome of the basking shark Cetorhinus maximus
(Chondrichthyes, Cetorhinidae).
AB - The basking shark (Cetorhinus maximus) is the world's second largest fish and the
subject of strong conservation concern. Minimal genetic assessment exists for
this globally distributed but regionally endangered species. We describe the
complete mitochondrial genome sequence of C. maximus, obtained via polymerase
chain reaction-based Sanger sequencing. The total length of the mitogenome is
16,670 bp and consists of 2 rRNAs, 22 tRNAs and 13 protein-coding genes. The base
composition has an A + T bias (63.6%), as is often seen in other sharks. Gene
order is equivalent to that found in most vertebrates.
PMID- 24354742
TI - Absolute quantitation of low abundance plasma APL1beta peptides at sub-fmol/mL
Level by SRM/MRM without immunoaffinity enrichment.
AB - Selected/multiple reaction monitoring (SRM/MRM) has been widely used for the
quantification of specific proteins/peptides, although it is still challenging to
quantitate low abundant proteins/peptides in complex samples such as
plasma/serum. To overcome this problem, enrichment of target proteins/peptides is
needed, such as immunoprecipitation; however, this is labor-intense and
generation of antibodies is highly expensive. In this study, we attempted to
quantify plasma low abundant APLP1-derived Abeta-like peptides (APL1beta), a
surrogate marker for Alzheimer's disease, by SRM/MRM using stable isotope-labeled
reference peptides without immunoaffinity enrichment. A combination of Cibacron
Blue dye mediated albumin removal and acetonitrile extraction followed by C18
strong cation exchange multi-StageTip purification was used to deplete plasma
proteins and unnecessary peptides. Optimal and validated precursor ions to
fragment ion transitions of APL1beta were developed on a triple quadruple mass
spectrometer, and the nanoliquid chromatography gradient for peptide separation
was optimized to minimize the biological interference of plasma. Using the stable
isotope-labeled (SI) peptide as an internal control, absolute concentrations of
plasma APL1beta peptide could be quantified as several hundred amol/mL. To our
knowledge, this is the lowest detection level of endogenous plasma peptide
quantified by SRM/MRM.
PMID- 24354743
TI - Is breastfeeding in infancy predictive of child mental well-being and protective
against obesity at 9 years of age?
AB - BACKGROUND: Preventing child mental health problems and child obesity have been
recognized as public health priorities. The aim of the present study was to
examine whether being breastfed (at all or exclusively) in infancy was a
predictor of mental well-being and protective against risk of obesity at age 9.
METHODS: Cross-sectional data from a large, nationally representative cohort
study in the Republic of Ireland was used (n = 8357). Data on breastfeeding were
retrospectively recalled. Child mental well-being was assessed using a parent
completed Strengths and Difficulties Questionnaire (SDQ). Child's height and
weight were measured using scientifically calibrated instruments. RESULTS:
Logistic regression analyses indicated that, after controlling for a wide range
of potential confounding variables, being breastfed in infancy was associated
with a 26% (P < 0.05) reduction in the risk of an abnormal SDQ score at 9 years.
Being breastfed remained a significant predictor of child mental well-being when
child obesity was controlled for, indicating that being breastfed, independent of
child obesity, is a predictor of child mental well-being. The results of a second
logistic regression indicated that, after controlling for a wide range of
potential confounding variables, being breastfed for between 11 and 25 weeks was
associated with a 36% (P < 0.05) reduction in the risk of obesity at 9 years,
while being breastfed for 26 weeks or longer was associated with a 48% (P < 0.01)
reduction in the risk of obesity at 9 years. CONCLUSIONS: Breastfeeding in
infancy may protect against both poor mental well-being and obesity in childhood.
PMID- 24354744
TI - The effect of evaluation on co-occurrence memory judgement.
AB - Three experiments tested the effect of an attitude towards an object on the
memory judgement of whether this object co-occurred with positive versus negative
stimuli. We induced positive or negative attitudes towards novel male stimuli,
and paired each man with an equal number of positive and negative animals. In a
memory test, participants reported more co-occurrences of same-valence man/animal
pairs than opposite-valence pairs. This valence-compatibility effect occurred
even when attitudes were induced after the pairing (Experiment 1), when
participants knew that each man occurred with an equal number of positive and
negative animals (Experiment 2), and in reports of clear memory of pairs that did
not co-occur (Experiment 3). The present findings suggest that evaluation causes
illusory correlation even when the co-occurring stimuli are not traits or
behaviours attributed to the attitude object. The results question the validity
of co-occurrence memory judgements as measures of co-occurrence awareness in
evaluative conditioning (EC) research.
PMID- 24354745
TI - Living with a powered wheelchair: exploring children's and young people's
experiences.
AB - PURPOSE: The study aimed to explore the lived experiences of children and young
people who use an Electric Powered Indoor/Outdoor wheelchair (EPIOC). METHOD: To
allow for the individual lived experiences of the children to be explored, an
exploratory study was designed using Interpretative Phenomenological Analysis
(IPA). Nine children aged 7-16 years were recruited and their views explored
through semi-structured interviews. RESULTS: Children appeared to be working to
achieve an adequate fit between self, the EPIOC and the environment. Where an
adequate fit was achieved the child experienced positive consequences of using an
EPIOC including increased participation and positive feelings. However an
inadequate fit led to negative experiences including reduced participation, fear
and anxiety. The changing interface between self, EPIOC and environment appeared
to be important in shaping these experiences. CONCLUSIONS: This study adds to
understanding the ambiguous experience of being a child EPIOC user and the need
for ongoing support from services especially around stages of transition. It also
contributes to the development of the social model of disability from a child's
perspective. Implications for Rehabilitation Children who use Electric Powered
Indoor/Outdoor Chairs have both positive and negative experiences which are
dependent on the fit of the child, chair and the environment. Child EPIOC users
are active agents in shaping their experiences. Children who use an EPIOC maybe
particularly at risk of reduced participation, especially at times when their
environment changes significantly such as when leaving school or college.
PMID- 24354747
TI - Need to focus beyond the medical causes: a systematic review of the social
factors affecting neonatal deaths.
AB - BACKGROUND: Reducing the global total of 3.3 million neonatal deaths is crucial
to meeting the fourth Millennium Development Goal. Until recently, attention has
been on the medical causes of the neonatal deaths, while the social factors
contextualising these deaths have largely remained unaddressed. The current
review aimed to quantify the role of these factors in neonatal deaths. METHODS: A
systematic search was performed through PubMed, Google scholar, Cochrane library,
Medline, IndMed, Embase, World Health Organization and Biomed central databases.
Studies published from 1995 to 2011 were included. Random effects meta-analysis
was performed to derive at an estimate of the burden of delays, as defined by the
'three delays model' by Thadeus and Maine. RESULTS: A total of 17 studies were
reviewed. The majority of them (n = 10) were from the African continent. Level 3
delay, i.e. delay in receiving appropriate treatment upon reaching a health
facility (38.7%, 95% CI, 21.7%-57.3%) and delay in deciding to seek care for the
illness (Level 1 delay) (28%, 95% CI, 16%-43%) were the major contributors to
neonatal deaths. Level 2 delay, i.e. delay in reaching a health facility (18.3%,
95% CI, 2.6-43.8%) contributed least to the neonatal deaths. CONCLUSION: Creating
awareness among caregivers regarding early recognition and treatment seeking for
neonatal illness along with improving the quality of neonatal care provided at
the health facilities is essential to reduce neonatal mortality.
PMID- 24354748
TI - Pregnancy planning, smoking behaviour during pregnancy, and neonatal outcome: UK
Millennium Cohort Study.
AB - BACKGROUND: Pre-pregnancy health and care are important for the health of the
future generations. Smoking during pregnancy has been well-researched and there
is clear evidence of harm. But there has been little research on the health
impact of planning for pregnancy. This study aims to investigate the independent
effects of pregnancy planning and smoking during pregnancy on neonatal outcome.
METHODS: This analysis made use of data from the UK Millennium Cohort Study. The
study sample consisted of 18,178 singleton babies born in UK between 2000 and
2001. The neonatal outcomes of interest were low birthweight (<2.5 Kg) and pre
term birth (<37 completed weeks gestation). Logistic regression was used to
estimate the association between pregnancy planning and/or smoking and neonatal
outcome. Adjusted odds ratios were used to calculate population attributable risk
fractions (PAFs). RESULTS: 43% of mothers did not plan their pregnancy and 34%
were smoking just before and/or during pregnancy. Planners were half as likely to
be smokers just before pregnancy, and more likely to give up or reduce the amount
smoked if smokers. Unplanned pregnancies had 24% increased odds of low birth
weight and prematurity compared to planned pregnancies (AORLBW1.24, 95% CI 1.04
1.48; AORPREM1.24, 95% CI 1.05-1.45), independent of smoking status. The odds of
low birth weight for babies of mothers who were smoking just before pregnancy was
91% higher than that of mothers who were not (AORLBW1.91, 95% CI 1.56-2.34).
Women who quit or reduced the amount smoked during pregnancy lowered the risk of
a low birth weight baby by one third (AORLBW0.66, 95% CI 0.51-0.85) compared with
women whose smoking level did not change. Smaller effects were found for
prematurity. If all women planned their pregnancy and did not smoke before or
during pregnancy, 30% of low birthweight and 14% of prematurity could, in theory,
be avoided. CONCLUSIONS: Planning a pregnancy and avoiding smoking during
pregnancy has clear, independent, health benefits for babies. Quitting or
reducing the amount smoked during pregnancy can reduce the risk of low
birthweight.
PMID- 24354749
TI - Advances in 4D treatment planning for scanned particle beam therapy - report of
dedicated workshops.
AB - We report on recent progress in the field of mobile tumor treatment with scanned
particle beams, as discussed in the latest editions of the 4D treatment planning
workshop. The workshop series started in 2009, with about 20 people from 4
research institutes involved, all actively working on particle therapy delivery
and development. The first workshop resulted in a summary of recommendations for
the treatment of mobile targets, along with a list of requirements to apply these
guidelines clinically. The increased interest in the treatment of mobile tumors
led to a continuously growing number of attendees: the 2012 edition counted more
than 60 participants from 20 institutions and commercial vendors. The focus of
research discussions among workshop participants progressively moved from 4D
treatment planning to complete 4D treatments, aiming at effective and safe
treatment delivery. Current research perspectives on 4D treatments include all
critical aspects of time resolved delivery, such as in-room imaging, motion
detection, beam application, and quality assurance techniques. This was motivated
by the start of first clinical treatments of hepato cellular tumors with a
scanned particle beam, relying on gating or abdominal compression for motion
mitigation. Up to date research activities emphasize significant efforts in
investigating advanced motion mitigation techniques, with a specific interest in
the development of dedicated tools for experimental validation. Potential
improvements will be made possible in the near future through 4D optimized
treatment plans that require upgrades of the currently established therapy
control systems for time resolved delivery. But since also these novel
optimization techniques rely on the validity of the 4DCT, research focusing on
alternative 4D imaging technique, such as MRI based 4DCT generation will
continue.
PMID- 24354750
TI - Commissioning of an integrated platform for time-resolved treatment delivery in
scanned ion beam therapy by means of optical motion monitoring.
AB - The integrated use of optical technologies for patient monitoring is addressed in
the framework of time-resolved treatment delivery for scanned ion beam therapy. A
software application has been designed to provide the therapy control system
(TCS) with a continuous geometrical feedback by processing the external
surrogates tridimensional data, detected in real-time via optical tracking.
Conventional procedures for phase-based respiratory phase detection were
implemented, as well as the interface to patient specific correlation models, in
order to estimate internal tumor motion from surface markers. In this paper,
particular attention is dedicated to the quantification of time delays resulting
from system integration and its compensation by means of polynomial interpolation
in the time domain. Dedicated tests to assess the separate delay contributions
due to optical signal processing, digital data transfer to the TCS and passive
beam energy modulation actuation have been performed. We report the system
technological commissioning activities reporting dose distribution errors in a
phantom study, where the treatment of a lung lesion was simulated, with both
lateral and range beam position compensation. The zero-delay systems integration
with a specific active scanning delivery machine was achieved by tuning the
amount of time prediction applied to lateral (14.61 +/- 0.98 ms) and depth (34.1
+/- 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy
in forward estimation. Direct optical target observation and motion phase (MPh)
based tumor motion discretization strategies were tested, resulting in 20.3(2.3)%
and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to
static irradiation, respectively. Results confirm the technical feasibility of
the implemented strategy towards 4D treatment delivery, with negligible
percentual dose deviations with respect to static irradiation.
PMID- 24354751
TI - IMRT treatment planning on 4D geometries for the era of dynamic MLC tracking.
AB - The problem addressed here was to obtain optimal and deliverable dynamic
multileaf collimator (MLC) leaf sequences from four-dimensional (4D) geometries
for dynamic MLC tracking delivery. The envisaged scenario was where respiratory
phase and position information of the target was available during treatment, from
which the optimal treatment plan could be further adapted in real time. A tool
for 4D treatment plan optimization was developed that integrates a commercially
available treatment planning system and a general-purpose optimization system.
The 4D planning method was applied to the 4D computed tomography planning scans
of three lung cancer patients. The optimization variables were MLC leaf positions
as a function of monitor units and respiratory phase. The objective function was
the deformable dose-summed 4D treatment plan score. MLC leaf motion was
constrained by the maximum leaf velocity between control points in terms of
monitor units for tumor motion parallel to the leaf travel direction and between
phases for tumor motion parallel to the leaf travel direction. For comparison and
a starting point for the 4D optimization, three-dimensional (3D) optimization was
performed on each of the phases. The output of the 4D IMRT planning process is a
leaf sequence which is a function of both monitor unit and phase, which can be
delivered to a patient whose breathing may vary between the imaging and treatment
sessions. The 4D treatment plan score improved during 4D optimization by 34%, 4%,
and 50% for Patients A, B, and C, respectively, indicating 4D optimization
generated a better 4D treatment plan than the deformable sum of individually
optimized phase plans. The dose-volume histograms for each phase remained
similar, indicating robustness of the 4D treatment plan to respiratory variations
expected during treatment delivery. In summary, 4D optimization for respiratory
phase-dependent treatment planning with dynamic MLC motion tracking improved the
4D treatment plan score by 4-50% compared with 3D optimization. The 4D treatment
plans had leaf sequences that varied from phase to phase to account for anatomic
motion, but showed similar target dose distributions in each phase. The current
method could in principle be generalized for use in offline replanning between
fractions or for online 4D treatment planning based on 4D cone-beam CT images.
Computation time remains a challenge.
PMID- 24354752
TI - Multigating, a 4D optimized beam tracking in scanned ion beam therapy.
AB - The treatment of moving tumors with a scanned ion beam is challenging due to
interplay effects and changing beam range. We propose multigating, as a method
for 4D-treatment optimization and delivery. In 3D beam tracking, tracking vectors
are added during delivery to beam spot positions based on the detected motion
phase. This has the disadvantage of dose errors in case of complex motion
patterns and an uncertain out-of-target dose distribution. In multigating, the
motion phase for each beam spot is predefined, which allows to add the tracking
vector prior to beam weight optimization on all motion phases. The
synchronization of delivery and target motion is assured by fast gating. The
feasibility of the delivery was shown in a film experiment and required only
minor software modification to the treatment planning system. In a treatment
planning study in 4 lung cancer patients, target coverage could be restored to
the level of a static reference plan by multigating (V95 > 99%) but not by
standard beam tracking (V95 < 95%). The conformity of the multigating plans was
only slightly lower than those of the static plan, with a conformity number of
72.0% (median, range 64.6-76.6%) compared to 75.8% (70.8-81.5%) in spite of
target motion of up to 22 mm. In conclusion, we showed the technical feasibility
of multigating, a 4D-optimization and delivery method using scanned beams that
allows for conformal and homogeneous dose delivery to moving targets also in case
of complex motion.
PMID- 24354753
TI - Sodium-iodine symporter gene expression controlled by the EGR-1 promoter:
biodistribution, imaging and in vitro radionuclide therapy with Na(131)I.
AB - The objective of this study is to explore the feasibility of radioiodine
treatment for cervical cancer using the early growth response (Egr-1) promoter to
control sodium-iodine symporter (hNIS) gene expression. The hNIS gene was
previously transfected into Hela cells under the control of either the
cytomegalovirus (CMV) or Egr-1 promoters. Na(125)I uptake was measured in the
presence or absence of NaClO4. Na(125)I efflux was measured. The effects of
external beam radiation on iodine uptake and retention were studied. The
cytotoxic effects of (131)I were measured by clonogenic assay. The Na(125)I
biodistribution was obtained using mice bearing control and transfected cells.
The %ID/g of tumor and major organs were obtained for a range of times up to 48
hours post injection and the ratio of tumor to non-tumor activity (T/NT) was
calculated. Tumors were imaged with Na(131)I and (99m)TcO4 (-), and the ratio of
tumor to background activity (T/B) was calculated. Na(125)I uptake in Hela cells
was minimal in the absence of hNIS. Uptake in the transfected cells was strong,
and could be blocked by NaClO4. The iodine uptake of Hela-Egr-1-hNIS cells
increased after the irradiation, and the magnitude of this effect approximately
matched the radiation dose delivered. The efflux of 125I was affected by neither
the promoter sequence nor pre-irradiation. (131)I reduced the clonogenic survival
of symporter expressing cells, relative to the parental line. The effect was
greatest in cells where hNIS was driven by the CMV promoter. Tumors formed from
Hela-Egr-1-hNIS concentrated Na(125)I over a 12 hour period, in contrast to
untransfected cells. These tumors could also be successfully imaged using either
Na(131)I or (99m)TcO4 (-). (131)I uptake peaked at 4h, while (99m)TcO4 (-)
accumulated over approximately 20 hours. In vivo uptake of (131)I and (99m)TcO4 (
) was slightly higher in cells transfected with the Egr-1 promoter, compared to
CMV. Hela-Egr-1-hNIS cells demonstrate highly enhanced iodine uptake, and this
effect is further augmented by radiation, creating a positive feedback loop which
may bolster radionuclide therapy in vivo.
PMID- 24354755
TI - Clinical immobilization techniques for proton therapy.
AB - Proton therapy through the use of the Bragg peak affords clinicians a tool with
which highly conformal dose can be delivered to the target while minimizing
integral dose to surrounding healthy tissue. To gain maximum benefit from proton
therapy adequate patient immobilization must be maintained to ensure accurate
dose delivery. While immobilization in external beam radiation therapy is
designed to minimize inter- and intra-fraction target motion, in proton therapy
there are other additional aspects which must be considered, chief of which is
accurately determining and maintaining the targets water-equivalent depth along
the beam axis. Over the past 23 years of treating with protons, the team at the
James M. Slater Proton Treatment and Research Center at Loma Linda University
Medical Center have developed and implemented extensive immobilization systems to
address the specific needs of protons. In this publication we review the
immobilization systems that are used at Loma Linda in the treatment of head and
neck, prostate, upper GI, lung and breast disease, along with a description of
the intracranial radiosurgery immobilization system used in the treatment of
brain metastasis and arteriovenous malformations (AVM's).
PMID- 24354754
TI - On voxel-by-voxel accumulated dose for prostate radiation therapy using
deformable image registration.
AB - Since delivered dose is rarely the same with planned, we calculated the delivered
total dose to ten prostate radiotherapy patients treated with rectal balloons
using deformable dose accumulation (DDA) and compared it with the planned dose.
The patients were treated with TomoTherapy using two rectal balloon designs: five
patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM
balloon (balloon B). Prostate and rectal wall contours were outlined on each pre
treatment MVCT for all patients. Delivered fractional doses were calculated using
the MVCT taken immediately prior to delivery. Dose grids were accumulated to the
last MVCT using DDA tools in Pinnacle3 TM (v9.100, Philips Radiation Oncology
Systems, Fitchburg, USA). Delivered total doses were compared with planned doses
using prostate and rectal wall DVHs. The rectal NTCP was calculated based on
total delivered and planned doses for all patients using the Lyman model. For
8/10 patients, the rectal wall NTCP calculated using the delivered total dose was
less than planned, with seven patients showing a decrease of more than 5% in
NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total
delivered dose was 2% higher than planned. This study indicates that for patients
receiving hypofractionated radiotherapy for prostate cancer with a rectal
balloon, total delivered doses to prostate is similar with planned while
delivered dose to rectal walls may be significantly different from planned doses.
8/10 patients show significant correlation between rectal balloon anterior
posterior positions and some VD values.
PMID- 24354757
TI - Strategic steps for advanced molecular imaging with magnetic resonance-based
diagnostic modalities.
AB - With the rapidly-expanding sophistication in our understanding of cancer cell
biology, molecular imaging offers a critical bridge to oncology. Molecular
imaging through magnetic resonance spectroscopy (MRS) can provide information
about many metabolites at the same time. Since MRS entails no ionizing radiation,
repeated monitoring, including screening can be performed. However, MRS via the
fast Fourier transform (FFT) has poor resolution and signal-to-noise ratio (SNR).
Moreover, subjective and non-unique (ambiguous) fittings of FFT spectra cannot
provide reliable quantification of clinical usefulness. In sharp contrast,
objective and unique (unambiguous) signal processing by the fast Pade transform
(FPT) can increase resolution and retrieve the true quantitative metabolic
information. To illustrate, we apply the FPT to in vitro MRS data as encoded from
malignant ovarian cyst fluid and perform detailed analysis. This problem area is
particularly in need of timely diagnostics by more advanced modalities, such as
high-resolution MRS, since conventional methods usually detect ovarian cancers at
late stages with poor prognosis, whereas at an early stage the prognosis is
excellent. The reliability and robustness of the FPT is assessed for time signals
contaminated with varying noise levels. In the presence of higher background
noise, all physical metabolites were unequivocally identified and their
concentrations precisely extracted, using small fractions of the total signal
length. Via the "signal-noise separation" concept alongside the "stability test",
all non-physical information was binned, such that fully denoised spectra were
generated. These results imply that a reformulation of data acquisition is
needed, as guided by the FPT in MRS, since a small number of short transient time
signals can provide high resolution and good SNR. This would enhance the
diagnostic accuracy of MRS and shorten examination times, thereby improving
efficiency and cost-effectiveness of this high throughput cancer diagnostic
modality. Such advantages could be particularly important for more effective
ovarian cancer detection, as well as more broadly for improved diagnostics and
treatment within oncology.
PMID- 24354758
TI - Pruritus: do Adelta fibers play a role?
AB - Neuropathological and molecular basis of pruritus has not been clarified and the
presence of certain specific neural circuits have been proposed. Our aim in this
study was to evaluate the role of Adelta fibers in the neural circuits of
pruritus by cutaneous silent period (CSP). Thirty-six patients with chronic
idiopathic generalized pruritus and 32 healthy controls were enrolled in the
study. CSP and nerve conduction studies of upper and lower extremities were
performed in both groups. Latencies of CSP in the upper and lower extremities
were observed to be prolonged in the patient group compared with the controls
while durations were shortened (all P < 0.001). However, these values were not
correlated with sex, age, duration or severity of the disease (all P > 0.05). Our
data suggest that pruritus may be developed by a nerve conduction abnormality in
the afferent fibers of Adelta, or cortical hypersensitivity, abnormality of the
cortical inhibitory mechanisms or lack of inhibition in the intermediate spinal
inhibitory neurons generating CSP. This topic needs to be evaluated thoroughly in
larger series with more detailed studies.
PMID- 24354756
TI - Small portable interchangeable imager of fluorescence for fluorescence guided
surgery and research.
AB - Fluorescence guided surgery (FGS) is a developing field of surgical and oncologic
research. Practically, FGS has shown useful applications in urologic surgery,
benign biliary surgery, colorectal cancer liver metastasis resection, and ovarian
cancer debulking. Most notably in in cancer surgery, FGS allows for the clear
delineation of cancerous tissue from benign tissue. FGS requires the utilization
of a fluorescent contrast agent and an intraoperative fluorescence imaging device
(IFID). Currently available IFIDs are expensive, unable to work with multiple
fluorophores, and can be cumbersome. This study aims to describe the development
and utility of a small, cost-efficient, and interchangeable IFID made from
commercially available components. Extensive research was done to design and
construct a light-weight, portable, and cost-effective IFID. We researched the
capabilities, size, and cost of several camera types and eventually decided on a
near-infrared (NIR) charged couple device (CCD) camera for its overall profile.
The small portable interchangeable imager of fluorescence (SPIIF) is a "scout"
IFID system for FGS. The main components of the SPIIF are a NIR CCD camera with
an articulating light filter. These components and a LED light source with an
attached heat sink are mounted on a small metal platform. The system is connected
to a laptop by a USB 2.0 cable. Pixielink (c) software on the laptop runs the
system by controlling exposure time, gain, and image capture. After developing
the system, we evaluated its utility as an IFID. The system weighs less than two
pounds and can cover a large area. Due to its small size, it is easily made
sterile by covering it with any sterile plastic sheet. To determine the system's
ability to detect fluorescent signal, we used the SPIIF to detect indocyanine
green under ex and in-vivo conditions and fluorescein under ex-vivo conditions.
We found the SPIIF was able to detect both ICG and fluorescein under different
depths of a semi-opaque colloid. Second, we found that a concentration as low as
0.5 g/ml of indocyanine green dissolved in plasma was detectable. Lastly, in a
murine and human cancer model, the SPIIF was able to detect indocyanine green
signal within tumors and generate a signal-to-background ratio (SBR) of 3.75.
This study shows that a low-cost IFID can be made from commercially available
parts. Second, this IFID is capable of in and ex-vivo detection of multiple
fluorophores without sacrificing its small size or favorable ergonomics.
PMID- 24354759
TI - The effects of mandatory preclinical education on exposure to injuries as
reported by Italian nursing students: a 15-year case-control, multicentre study.
PMID- 24354760
TI - Rapid remineralization of multiple disseminated bone lesions after high-dose
cytarabine in a patient with isolated myeloid sarcoma.
AB - Isolated myeloid sarcoma is a rare presentation of acute myeloid leukemia. There
are limited data available concerning the prognostic relevance and the right
treatment strategy for this clinical scenario. Here, we report a case of acute
myeloid leukemia with extensive lesions and fractures in multiple bones in a 64
yr-old male patient. Remarkably, treatment with a high-dose cytarabine regimen
led to rapid remineralization of all bone lesions and recovery of the patient's
mobility within a few weeks. Thereby, surgical treatment and radiotherapy could
be avoided, supporting the role of intensive induction and standard consolidation
chemotherapy as first-line treatment for myeloid sarcoma.
PMID- 24354761
TI - Trichogerminoma, a rare cutaneous follicular neoplasm with indolent clinical
course: report of two cases and review of literature.
AB - Trichogerminoma is a rare cutaneous adnexal neoplasm of the hair germ cell and
usually associated with benign clinical course and favorable outcome. Since its
first description by Sau et al. in 1992, only a few cases have been reported up
to date. Herein, we report two additional cases occurring in the hip and right
thigh, respectively. Both patients are male, one is 78 years old, the other is 29
years old. Histological examination reveals well-circumscribed dermal nodule
composed of lobules of basaloid cells with surrounding pseudocapsule. The
distinct characteristic of the tumor is that most of the lobules display a
special pattern of round nests or cell balls arranged in the central part with
the peripheral palisading. Immunostaining showed ring-like fashion of CK5/6, P63
and Bcl-2 with negative or weak staining in the "cell balls". There was no
recurrence after complete excision during the period of follow-up. To the best of
our knowledge, this is the first report of trichogerminoma in Chinese population.
In contrast to the previously reported cases, ours present the similar
morphological features with distinct immunohistochemical characteristics. We
consider the concept of trichogerminoma exists with no doubt by its identifiable
morphological features, and it should be classified as a variant of
trichoblastoma. Because of its malignant potential, complete excision is a prior
choice of treatment for this rare but distinctive tumor. VIRTUAL SLIDES: The
virtual slide(s) for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1558612241110439.
PMID- 24354762
TI - A silent mutation in mabA confers isoniazid resistance on Mycobacterium
tuberculosis.
AB - Drug resistance in Mycobacterium tuberculosis (Mtb) is caused by mutations in
restricted regions of the genome. Mutations in katG, the promoter region of the
mabA-inhA operon, and inhA are those most frequently responsible for isoniazid
(INH) resistance. Several INH-resistant (INH(r) ) Mtb clinical isolates without
mutations in these regions have been described, however, indicating that there
are as yet undetermined mechanisms of INH resistance. We identified the
mabA(g609a) silent mutation in a significant number of INH(r) Mtb clinical
isolates without known INH resistance mutations. A laboratory strain, H37Rv,
constructed with mabA(g609a) , was resistant to INH. We show here that the
mabA(g609a) mutation resulted in the upregulation of inhA, a gene encoding a
target for INH, converting the region adjacent to the mutation into an
alternative promoter for inhA. The mabA(g609a) silent mutation results in a novel
mechanism of INH resistance, filling in a missing piece of INH resistance in Mtb.
PMID- 24354764
TI - Measurement and prevalence of circulating ADAMTS13-specific immune complexes in
autoimmune thrombotic thrombocytopenic purpura.
AB - BACKGROUND: The formation of ADAMTS13-specific circulating immune complexes
(CICs) may be a pathophysiologic mechanism in autoimmune thrombotic
thrombocytopenic purpura (TTP), but has not been systematically investigated.
OBJECTIVES: (a) To develop an assay for ADAMTS13-specific CICs; (b) to evaluate
their prevalence in autoimmune TTP; and (c) to assess their association with
ADAMTS13-related measurements and clinical features in autoimmune TTP patients.
PATIENTS/METHODS: We developed and validated an ELISA method for ADAMTS13
specific CICs. ADAMTS13-specific CICs were searched for in 55 patients with
autoimmune TTP from the Milan TTP Registry (URL:http://www.ttpdatabase.org/) and
28 controls. The associations between ADAMTS13-specific CIC levels and ADAMTS13
activity, antigen, anti-ADAMTS13 IgGs and acute TTP clinical features were
assessed by multivariate linear regression. RESULTS: Intra- and inter-assay
coefficients of variation of the new test were 5.3 and 9.6%. In 36 patients with
severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, the prevalence of
ADAMTS13-specific CICs was 47% (n = 17; 95% confidence interval [CI], 32-63%).
ADAMTS13-specific CICs were detected also in seven of 19 (37%; 95% CI, 19-59%)
patients with reduced ADAMTS13 activity, but apparently negative anti-ADAMTS13
autoantibodies. ADAMTS13-specific CICs were not associated with ADAMTS13
activity, antigen or anti-ADAMTS13 IgGs. In patients with acute TTP, increasing
levels of ADAMTS13-specific CICs were associated with a higher number of plasma
exchange procedures required to attain remission (per 0.1 increase in normalized
OD values, beta, 2.9; 95% CI, -0.7 to 6.5). CONCLUSIONS: Approximately one to two
thirds of patients with autoimmune TTP display ADAMTS13-specific CICs. A thorough
investigation of the prognostic relevance of ADAMTS13-specific CIC levels in
autoimmune TTP is warranted.
PMID- 24354765
TI - Nonlinear pricing in drug benefits and medication use: the case of statin
compliance in Medicare Part D.
AB - OBJECTIVE: To examine how enrollees' statin compliance responds to expected
prices in Medicare Part D, which features a nonlinear price schedule due to a
coverage gap. DATA SOURCES/STUDY SETTING: Prescription Drug Event data for a 5
percent random sample of Medicare Advantage Prescription Drug Plan enrollees in
2008 who did not receive a low-income subsidy. STUDY DESIGN: We analyze statin
compliance prior to the coverage gap, where the "effective price" is higher than
the actual copayment for drugs because consumers anticipate that more spending
will make them more likely to reach the gap. We construct each enrollee's
effective price as her expected price at the end of the year, which is the
weighted average between pre-gap and in-gap copayments with the weight being the
predicted probability of hitting the gap. Compliance is defined as at least 80
percent of days covered. PRINCIPAL FINDINGS: Part D enrollees' pre-gap statin
compliance decreases by 3.7-4.7 percentage points for a $10 increase in the
effective price. CONCLUSION: The presence of a coverage gap decreases statin
compliance prior to the gap, suggesting that incorporating expected future prices
is important to assess the full impact of cost sharing on drug compliance under
nonlinear price schedules.
PMID- 24354763
TI - Issues in the timing of integrated early interventions: contributions from
nutrition, neuroscience, and psychological research.
AB - A central issue when designing multidimensional biological and psychosocial
interventions for children who are exposed to multiple developmental risks is
identification of the age period(s) in which such interventions will have the
strongest and longest lasting effects (sensitive periods). In this paper, we
review nutritional, neuroscientific, and psychological evidence on this issue.
Nutritional evidence is used to identify nutrient-sensitive periods of age-linked
dimensions of brain development, with specific reference to iron deficiency.
Neuroscience evidence is used to assess the importance of timing of exposures to
environmental stressors for maintaining neural, neuroendocrine, and immune
systems integrity. Psychological evidence illustrates the sensitivity of
cognitive and social-emotional development to contextual risk and protective
influences encountered at different ages. Evidence reviewed documents that the
early years of life are a sensitive period when biological or psychosocial
interventions or exposure to risk or protective contextual influences can produce
unique long-term influences upon human brain, neuroendocrine, and cognitive or
psychosocial development. However, the evidence does not identify the early years
as the sole sensitive time period within which to have a significant influence
upon development. Choice of age(s) to initiate interventions should be based on
what outcomes are targeted and what interventions are used.
PMID- 24354766
TI - Determining the price for pharmaceuticals in Germany: comparing a shortcut for
IQWiG's efficiency frontier method with the price set by the manufacturer for
ticagrelor.
AB - Under the recently enacted pharmaceutical price and reimbursement regulation in
Germany, manufacturers and payers negotiate an appropriate reimbursement price
for new products. If one of the parties involved wishes so, a formal evaluation
of costs and benefits will be conducted by the Institute for Quality and
Efficiency in Health Care (IQWiG). IQWiG makes recommendations for a
reimbursement price based on the 'efficiency frontier' in a therapeutic area. The
analysis requires, when applicable, to calculate savings in other areas of the
healthcare system (cost offsets) and healthcare costs during the years of life
gained (i.e., downstream costs). A recent paper described the conditions under
which calculation of downstream costs is not required. The purpose of this study
is to use the drug ticagrelor as an example to demonstrate this shortcut for the
efficiency frontier method. The analysis shows that applying the IQWiG approach
would result in substantial savings.
PMID- 24354767
TI - Long-term day-and-night rotating shift work poses a barrier to the normalization
of alanine transaminase.
AB - To evaluate the impact of day-and-night rotating shift work (RSW) on liver
health, we performed a retrospective analysis of the association between long
term RSW exposure and the normalization of plasma alanine transaminase (ALT)
levels over a five-year period. The data from physical examinations, blood tests,
abdominal sonographic examinations, personal histories, and occupational records
were collected from a cohort of workers in a semiconductor manufacturing company.
The sample population was divided into three subgroups for analysis, according to
self-reported shift work status over the five-year interval: persistent daytime
workers, workers exposed intermittently to RSW (i-RSW), and workers exposed
persistently to RSW (p-RSW). Records were analyzed for 1196 male workers with an
initial mean age of 32.5 years (SD 6.0 years), of whom 821 (68.7%) were
identified as rotating shift workers, including 374 i-RSW (31.3%) and 447 p-RSW
workers (37.4%). At the beginning of the follow-up, 275 were found to have
elevated ALT (e-ALT): 25.1% daytime workers, 23.0% i-RSW workers, and 21.3% p-RSW
workers (p = 0.098). Of those with e-ALT at the beginning, 101 workers showed
normalized serum ALT levels at the end of five-year follow-up: 40 (10.7%) of 375
daytime workers, 32 (8.6%) of 374 i-RSW workers, and 29 (6.5%) of 447 p-RSW
workers (p = 0.016). Compared with the workers having persistent e-ALT at the end
of follow-up, the workers normalized serum ALT levels had significantly lesser
exposures to RSW during follow-up. By performing multivariate logistic regression
analyses, and comparing with the persistent daytime co-workers, after controlling
for confounding variables (age, occupational factors, educational levels,
lifestyle factors, metabolic syndrome, hepatovirus infection, and fatty liver),
analysis indicated that the workers exposed to p-RSW were 46% less likely (OR,
0.54; 95% CI, 0.30-0.95; p = 0.03) to attain normal ALT levels within a five-year
interval. These observations demonstrate that persistent day-and-night RSW pose a
vigorous obstacle to the normalization of e-ALT among workers with preexisting
abnormal liver function. We suggest that workers and managers approach with
caution the consideration of assigning or accepting long-term day-and-night RSW
when an employee health screening shows evidence of abnormal liver function.
PMID- 24354768
TI - Medium-chain dehydrogenases with new specificity: amino mannitol dehydrogenases
on the azasugar biosynthetic pathway.
AB - Azasugar biosynthesis involves a key dehydrogenase that oxidizes 2-amino-2-deoxy
D-mannitol to the 6-oxo compound. The genes encoding homologous NAD-dependent
dehydrogenases from Bacillus amyloliquefaciens FZB42, B. atrophaeus 1942, and
Paenibacillus polymyxa SC2 were codon-optimized and expressed in BL21(DE3)
Escherichia coli. Relative to the two Bacillus enzymes, the enzyme from P.
polymyxa proved to have superior catalytic properties with a Vmax of 0.095 +/-
0.002 umol/min/mg, 59-fold higher than the B. amyloliquefaciens enzyme. The
preferred substrate is 2- amino-2-deoxy-D-mannitol, though mannitol is accepted
as a poor substrate at 3% of the relative rate. Simple amino alcohols were also
accepted as substrates at lower rates. Sequence alignment suggested D283 was
involved in the enzyme's specificity for aminopolyols. Point mutant D283N lost
its amino specificity, accepting mannitol at 45% the rate observed for 2-amino-2
deoxy-D-mannitol. These results provide the first characterization of this class
of zinc-dependent medium chain dehydrogenases that utilize aminopolyol
substrates.
PMID- 24354769
TI - Design of a serum stability tag for bioactive peptides.
AB - Serum has a high intrinsic proteolytic activity that leads to continuous
processing of peptides and proteins. Strategies to protect bioactive peptides
from serum proteolytic degradation include incorporation of unnatural amino
acids, conformational constraints, large polymeric tags, or other synthetic
manipulations such as amide bond replacements. Here we explored a possibility of
designing a serum stability tag made of natural amino acids. We observed that a
diproline motif (-Pro-Pro-) shows remarkable stability against serum
endopeptidases. Accordingly, we designed close to 50 peptides to identify natural
amino acids flanking the -Pro-Pro- sequence that can enhance the serum stability
of this motif. As a result, a tetrapeptide with the sequence Asp-Pro-Pro-Glu
(DPPE) was identified that remains intact in human serum for more than 24 h. at
37 degrees C.
PMID- 24354770
TI - Influence of selected factors on veins' permeability for albumin in vitro.
AB - We present the results of a study on the influence of albumin and prolactin
concentrations and intravascular fluid pH on vein permeability for albumin.
Permeability conditions were simulated depending on albumin concentration, pH
value and prolactin concentration. In research model an in vitro method was
applied using natural membrane - porcine vena cava inferior. Vein permeability
was in the 0.63% to 5.69% range. In control variant permeability was ~2.54% and
increased ~2 fold at decreased albumin and PRL concentrations. At increased
albumin concentration permeability was decreased 4-fold. Albumin concentration
significantly influences albumin permeability.
PMID- 24354771
TI - Detection and localization of methionine sulfoxide residues of specific proteins
in brain tissue.
AB - Methionine sulfoxide is a common posttranslational oxidative modification that
can alter protein function. Vulnerability of specific proteins to methionine
oxidation varies and depends on their structure. In the current study, detection
of methionine sulfoxide in intact proteins is mediated by novel anti-methionine
sulfoxide antibody that resulted in the identification of three major methionine
sulfoxide-proteins in brain: bisphosphate aldolase A and C, alpha and beta
subunits of hemoglobin, and serum albumin. The locations of the methionine
sulfoxide residues were determined by massspectrometry analyses. It is suggested
that the in vivo methionine oxidation of these proteins represent early
posttranslational oxidative modification of proteins in brain. Thus, elevated
levels of methionine-sulfoxide in these proteins may serve as bio-markers for
enhanced oxidative stress in brain, which may be associated with brain disorders
and diseases.
PMID- 24354772
TI - Construction and characterization of novel hirulog variants with antithrombin and
antiplatelet activities.
AB - The RGD sequence was used to design potent hirudin isoform 3 mimetic peptides
with both antithrombin activity and antiplatelet aggregation activity. The RGD
and proline were inserted between the catalytic active binding domain (D-Phe-Pro
Arg-Pro) on the N-terminus and the anion-binding exosite binding domain
(QGDFEPIPEDAYDE) on the Cterminus. Thrombin titration assay and ATP-induced
platelet aggregation test revealed that the peptide with the linker RGDWP or
RGDGP possessed potent antithrombin and antiplatelet activities, while other
peptides without the Pro residue in the linker only showed antithrombin activity.
Similar results were obtained in the RGD-containing hirulog-1 variants. Our study
indicates that the inserted Pro residue facilitates the exposure of RGD and the
binding of the peptide to glycoprotein IIb/IIIa (GPIIb/IIIa). The strategy of
combining the RGD sequence and the Pro residue may be used for future designs of
bifunctional antithrombotic agents.
PMID- 24354773
TI - Identification of an amyloidogenic peptide from the Bap protein of Staphylococcus
epidermidis.
AB - Biofilm associated proteins (Bap) are involved in the biofilm formation process
of several bacterial species. The sequence STVTVT is present in Bap proteins
expressed by many Staphylococcus species, Acinetobacter baumanii and Salmonella
enterica. The peptide STVTVTF derived from the C-repeat of the Bap protein from
Staphylococcus epidermidis was selected through the AGGRESCAN, PASTA, and TANGO
software prediction of protein aggregation and formation of amyloid fibers. We
characterized the self-assembly properties of the peptide STVTVTF by different
methods: in the presence of the peptide, we observed an increase in the
fluorescence intensity of Thioflavin T; many intermolecular beta-sheets and
fibers were spontaneously formed in peptide preparations as observed by infrared
spectroscopy and atomic force microscopy analyses. In conclusion, a 7 amino acids
peptide derived from the C-repeat of the Bap protein was sufficient for the
spontaneous formation of amyloid fibers. The possible involvement of this
amyloidogenic sequence in protein-protein interactions is discussed.
PMID- 24354774
TI - Untargeted metabolomic profiling in saliva of smokers and nonsmokers by a
validated GC-TOF-MS method.
AB - A GC-TOF-MS method was developed and validated for a metabolic fingerprinting in
saliva of smokers and nonsmokers. We validated the method by spiking 37 different
metabolites and 6 internal standards to saliva between 0.1 MUM and 2 mM. Intraday
coefficients of variation (CVs) (accuracies) were on average, 11.9% (85.8%), 8.2%
(88.9%), and 10.0% (106.7%) for the spiked levels 25, 50, and 200 MUM,
respectively (N = 5). Interday CVs (accuracies) were 12.4% (97%), 18.8% (95.5%),
and 17.2% (105.9%) for the respective levels of 25, 50, and 200 MUM (N = 5). The
method was applied to saliva of smokers and nonsmokers, obtained from a 24 h diet
controlled clinical study, in order to identify biomarkers of endogenous origin,
which could be linked to smoking related diseases. Automated peak picking,
integration, and statistical analysis were conducted by the software tools
MZmine, Metaboanalyst, and PSPP. We could identify 13 significantly altered
metabolites in smokers (p < 0.05) by matching them against MS libraries and
authentic standard compounds. Most of the identified metabolites, including
tyramine, adenosine, and glucose-6-phosphate, could be linked to smoking-related
perturbations and may be associated with established detrimental effects of
smoking.
PMID- 24354776
TI - Weight status is associated with cross-sectional trajectories of motor co
ordination across childhood.
AB - BACKGROUND: Research indicates the development of motor co-ordination (MC) may be
an important contributing factor to positive or negative weight trajectories
across childhood. OBJECTIVES: To analyse cross-sectional associations between MC
and weight status in children (boys n = 3344 - girls n = 3281), aged 6-11 years
and assess overweight/obese risk across different ages. METHODS: Body mass index
(BMI) was calculated [body mass (kg)/height (m(2))]. MC was evaluated using the
Korperkoordination Test fur Kinder (KTK) and a motor quotient (MQ) was
calculated. MQ distribution data were split into tertiles. The effect of age, sex
and MQ tertiles on BMI and MC was tested with a factorial anova. A logistic
regression also was performed to calculate odd ratios (OR) for being
overweight/obese at each age. RESULTS: Children with higher MQ demonstrated lower
BMI levels (F(2,6224) = 222.09; P < 0.001). Differences in BMI among MQ tertiles
became larger across age (F(10,6224) = 4.53; P < 0.001). The OR of being
overweight/obese in both sexes within the lowest MQ tertile increased in each age
group from 6 to 11 years. Specifically, OR increased from 2.26 to 27.77 and from
1.87 to 6.81 in boys and girls respectively. CONCLUSIONS: Children with low
levels of MC have a higher risk of being overweight/obese and this risk increases
with age.
PMID- 24354775
TI - Cerebrospinal fluid cortisol and progesterone profiles and outcomes
prognostication after severe traumatic brain injury.
AB - Despite significant advances in the management of head trauma, there remains a
lack of pharmacological treatment options for traumatic brain injury (TBI). While
progesterone clinical trials have shown promise, corticosteroid trials have
failed. The purpose of this study was to (1) characterize endogenous
cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2)
determine relationships between CSF and serum profiles, and (3) assess the
utility of these hormones as predictors of long-term outcomes. We evaluated 130
adults with severe TBI. Serum samples (n=538) and CSF samples (n=746) were
collected for 6 days post-injury, analyzed for cortisol and progesterone, and
compared with healthy controls (n=13). Hormone data were linked with clinical
data, including Glasgow Outcome Scale (GOS) scores at 6 and 12 months. Group
based trajectory (TRAJ) analysis was used to develop temporal hormone profiles
delineating distinct subpopulations. Compared with controls, CSF cortisol levels
were significantly and persistently elevated during the first week after TBI, and
high CSF cortisol levels were associated with poor outcome. As a precursor to
cortisol, progesterone mediated these effects. Serum and CSF levels for both
cortisol and progesterone were strongly correlated after TBI relative to
controls, possibly because of blood-brain barrier disruption. Also,
differentially impaired hormone transport and metabolism mechanisms after TBI,
potential de novo synthesis of steroids within the brain, and the complex
interplay of cortisol and pro-inflammatory cytokines may explain these acute
hormone profiles and, when taken together, may help shed light on why
corticosteroid trials have previously failed and why progesterone treatment after
TBI may be beneficial.
PMID- 24354777
TI - Layering garments during rest and exercise in the cold (8 degrees C): wearer
responses and comparability with selected fabric properties.
AB - How garments contribute to performance of the clothing system during wear is of
interest, as is understanding the value of using fabric properties to inform end
use characteristics. To investigate the influences of layering upper-body
garments, four fabrics were used to construct two first-layer garments (wool and
polyester) and two outer-layer garments (wool and membrane laminate). Over six
sessions, 10 moderately trained males wore each first-layer garment as a single
layer and in combination with each outer-layer garment while resting, running and
walking in cold environmental conditions (8 +/- 1 degrees C, 81 +/- 4% RH). Here,
the type of garment arrangement worn (fabric type or number of layers) had little
influence on heart rate, core body temperature and change in body mass. Weighted
mean covered skin temperature was warmer and weighted mean next-to-skin vapour
pressure was typically higher (following the onset of exercise) with two layers
versus one. Differences among fabrics for individual properties were typically
overstated compared to differences among corresponding garments for physiological
and psychophysical variables under the conditions of this study. These findings
inform the interpretation of particular fabric properties and highlight issues to
be acknowledged during development/refinement of fabric test methods.
PRACTITIONER SUMMARY: We examined the way in which selected fibre, fabric and
garment (layering) characteristics contribute to performance of the clothing
system during wear under cold conditions. Selected properties of the constituent
fabrics were found to provide limited insight into how garments perform during
wear under the conditions of this study.
PMID- 24354779
TI - Recurrent cryptococcal immune reconstitution inflammatory syndrome in an HIV
infected patient after anti-retroviral therapy: a case report.
AB - Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) in HIV-infected
patients presents as a clinical worsening or new presentation of cryptococcal
disease as a result of anti-retroviral therapy mediated immune restoration.
Recurrent C-IRIS is a rare condition. Recently, recurrent C-IRIS involving the
central nervous system, which is thought to require prolonged or alternative
immunosuppressive therapy, has been described. Here, we present an unusual case
of recurrent C-IRIS, sequentially involving the central nervous system and lymph
nodes, in an HIV-infected patient after anti-retroviral therapy. While
corticosteroids were used to control the inflammatory cerebral cryptococcomas,
lymphadenitis that developed after cessation of corticosteroids resolved without
additional immunosuppressive or anti-inflammatory drugs. This case suggests the
possibility of site-specific recovery of pathogen-specific immune response after
anti-retroviral therapy. In this condition, each episode of C-IRIS may be treated
independently, and extended corticosteroids may not always be needed.
PMID- 24354778
TI - Race/ethnicity, educational attainment, and pregnancy complications in New York
City women with pre-existing diabetes.
AB - BACKGROUND: More women are entering pregnancy with pre-existing diabetes. Disease
severity, glycaemic control, and predictors of pregnancy complications may differ
by race/ethnicity or educational attainment, leading to differences in adverse
pregnancy outcomes. METHODS: We used linked New York City hospital record and
birth certificate data for 6291 singleton births among women with pre-existing
diabetes between 1995 and 2003. We defined maternal race/ethnicity as non
Hispanic white, non-Hispanic black, Hispanic, South Asian, and East Asian, and
education level as <12, 12, and >12 years. Our outcomes were pre-eclampsia,
preterm birth (PTB) (<37 weeks gestation and categorised as spontaneous or
medically indicated), as well as small-for-gestational age (SGA) and large-for
gestational age (LGA). Using multivariable binomial regression, we estimated the
risk ratios for pre-eclampsia, SGA, and LGA. We used multivariable multinomial
regression to estimate odds ratios (OR) for PTB. RESULTS: Compared with non
Hispanic white women with pre-existing diabetes, non-Hispanic black and Hispanic
women with pre-existing diabetes had a 1.50-fold increased risk of pre-eclampsia
compared with non-Hispanic whites with pre-existing diabetes, after full
adjustment. Non-Hispanic black and Hispanic women with pre-existing diabetes had
adjusted ORs of 1.72 [adj. 95% confidence interval (CI) 1.38, 2.15] and 1.65
[adj.95% CI 1.32, 2.05], respectively, for medically indicated PTB. South Asian
women with pre-existing diabetes had the highest risk for having an SGA infant
[adj. OR: 2.29; adj. 95% CI 1.73, 3.03]. East Asian ethnicity was not associated
with these pregnancy complications. CONCLUSIONS: Non-Hispanic black, Hispanic,
and South Asian women with pre-existing diabetes may benefit from targeted
interventions to improve pregnancy outcomes.
PMID- 24354780
TI - Histological subtypes and characteristic structures of HPV-associated
oropharyngeal carcinoma: study with Japanese cases.
AB - BACKGROUND: Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is
clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC).
This study aimed to determine the relationship between histological subtypes of
OPC and HPV status for Japanese cases and to identify histological structures of
HPV-OPC. METHODS: 66 OPC cases were categorized into conventional squamous cell
carcinoma (SCC) and the variants. Conventional SCC was subcategorized into
keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status
of all cases was determined using p16-immunohistochemistry and HPV-DNA ISH.
RESULTS: Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC
tended to be nHPV-OPC with statistical significance. Two histological structures,
abrupt keratinization, defined in the text, and comedo-necrosis among non
maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended
to exist for HPV-OPC with statistical significance. CONCLUSIONS: This study
showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two
histological structures, abrupt keratinization and comedo-necrosis among non
maturing island, were considered characteristic histological features of HPV-OPC.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1816432541113073.
PMID- 24354781
TI - Phase II study of i.v. interferon-gamma in Japanese patients with mycosis
fungoides.
AB - A multisite, open-label, non-randomized, single-arm phase II study was conducted
to evaluate the efficacy and safety profiles of interferon-gamma in Japanese
patients diagnosed with stage IA-IIIA mycosis fungoides (MF). Interferon-gamma
was administrated i.v. to 15 patients at a dose of 2 million Japan reference
units once daily over 5 days a week for the first 4 weeks, followed by subsequent
intermittent injection. The primary efficacy end-point was the overall skin
response during the study as assessed according to the evaluation criteria for
chemotherapeutics for malignant skin carcinomas. Of the 15 patients, 11 (73.3%)
achieved the objective response. Of the other four patients, three remained on
treatment during study with stable disease and one showed disease progression.
The median duration of stable disease was not reached but was 170 days or more
(range, 29 to >=253 days). As assessed according to the modified severity
weighted assessment tool, nine patients (60.0%) achieved the objective response.
The most common drug-related adverse event (AE) was influenza-like illness
occurring in all patients enrolled, which did not lead to discontinuation of the
study. Two serious AE were reported in two patients: aggravation of MF and
aggravation of cataract, neither of which was considered directly related to the
study drug. The patient with aggravation of MF died 50 days after the initiation
of the study treatment. Another patient was withdrawn from the study due to drug
related cough, which disappeared after discontinuation of the drug. Overall,
interferon-gamma was effective and well-tolerated in Japanese patients with MF.
PMID- 24354782
TI - Cross-cultural differences in processing of architectural ranking: evidence from
an event-related potential study.
AB - Visual object identification is modulated by perceptual experience. In a cross
cultural ERP study we investigated whether cultural expertise determines how
buildings that vary in their ranking between high and low according to the
Western architectural decorum are perceived. Two groups of German and Chinese
participants performed an object classification task in which high- and low
ranking Western buildings had to be discriminated from everyday life objects. ERP
results indicate that an early stage of visual object identification (i.e.,
object model selection) is facilitated for high-ranking buildings for the German
participants, only. At a later stage of object identification, in which object
knowledge is complemented by information from semantic and episodic long-term
memory, no ERP evidence for cultural differences was obtained. These results
suggest that the identification of architectural ranking is modulated by
culturally specific expertise with Western-style architecture already at an early
processing stage.
PMID- 24354783
TI - Critical appraisal: Cross-linkers and the dentin matrix.
AB - The formation of a hybrid layer is essential for successful dentin bonding and is
achieved by adhesive penetration between exposed collagen fibrils in the
demineralized dentin. Incomplete infiltration of the adhesive within the collagen
network results in exposed fibrils, which may suffer enzymatic degradation over
time. Methods to increase collagen resistance to proteinases (enzymes that
degrade proteins) have been studied. One particular approach is to use collagen
cross-linking agents that modify collagen through addition of specific or random
amino acid linkage between and within its molecules. This Critical Appraisal
provides information on the effects of various cross-linkers on dentin collagen
stability, dentin properties, and resin-dentin bond strengths, and calls for
critical thinking on the potential effects of this therapeutic approach.
PMID- 24354784
TI - My kingdom for a horse.
PMID- 24354785
TI - Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and
recovery sleep responses to stress in mice.
AB - FK506-binding protein 51 (FKBP51) is a co-chaperone of the glucocorticoid
receptor, functionally linked to its activity via an ultra-short negative
feedback loop. Thus, FKBP51 plays an important regulatory role in the
hypothalamic-pituitary-adrenocortical (HPA) axis necessary for stress adaptation
and recovery. Previous investigations illustrated that HPA functionality is
influenced by polymorphisms in the gene encoding FKBP51, which are associated
with both increased protein levels and depressive episodes. Because FKBP51 is a
key molecule in stress responses, we hypothesized that its deletion impacts
sleep. To study FKBP51-involved changes in sleep, polysomnograms of FKBP51
knockout (KO) mice and wild-type (WT) littermates were compared at baseline and
in the recovery phase after 6-h sleep deprivation (SD) and 1-h restraint stress
(RS). Using another set of animals, the 24-h profiles of hippocampal free
corticosterone levels were also determined. The most dominant effect of FKBP51
deletion appeared as increased nocturnal wake, where the bout length was
significantly extended while non-rapid eye movement sleep (NREMS) and rapid eye
movement sleep were rather suppressed. After both SD and RS, FKBP51KO mice
exhibited less recovery or rebound sleep than WTs, although slow-wave activity
during NREMS was higher in KOs, particularly after SD. Sleep compositions of KOs
were nearly opposite to sleep profiles observed in human depression. This might
result from lower levels of free corticosterone in FKBP51KO mice, confirming
reduced HPA reactivity. The results indicate that an FKBP51 deletion yields a pro
resilience sleep phenotype. FKBP51 could therefore be a therapeutic target for
stress-induced mood and sleep disorders.
PMID- 24354786
TI - Control of spontaneous ovarian tumors by CD8+ T cells through NKG2D-targeted
delivery of antigenic peptide.
AB - BACKGROUND: There is an urgent need to develop targeted therapies for the control
of advanced stage ovarian cancer because it is the most deadly gynecologic
cancer. Antigen-specific immunotherapy is a promising approach because of the
potential of the immune system to specifically target tumors without the toxicity
associated with traditional chemoradiation. However, one of the major limitations
for antigen-specific cancer immunotherapy is the pre-existing immune tolerance
against endogenous targeted tumor antigens that frequently evolves during
carcinogenesis. Here, we described the creation of a therapeutic agent comprised
of a tumor-homing module fused to a functional domain capable of selectively
rendering tumor cells sensitive to foreign antigen-specific CD8+ T cell-mediated
immune attack, thereby circumventing many aspects of immune tolerance. The tumor
homing module, NKG2D, specifically binds to NKG2D ligand that is commonly
overexpressed in ovarian tumors. The functional domain is comprised of the Fc
portion of IgG2a protein and foreign immunogenic CD8+ T cell epitope flanked by
furin cleavage sites (R), which can be recognized and cleaved by furin that is
highly expressed in the tumor microenvironment. RESULTS: We show that this
therapeutic chimeric protein specifically loaded antigenic epitope onto the
surface of NKG2D ligand-expressing ovarian tumor cells, rendering ovarian tumors
susceptible to antigen-specific CTL-mediated killing in vitro. Furthermore, we
show that intraperitoneal administration of our therapeutic chimeric protein
followed by adoptive transfer of antigen-specific CD8+ T cells generates potent
antitumor effects and significant accumulation of antigen-specific CD8+ T cells
in the tumor loci. CONCLUSIONS: Our findings have promise for bypassing immune
tolerance to enhance cancer immunotherapy.
PMID- 24354787
TI - The efficacy of a self-management programme for people with diabetes, after a
special training programme for healthcare workers in Taiwan: a quasi-experimental
design.
AB - AIMS AND OBJECTIVIES: To analyse the efficacy of improving disease management
after implementing a self-management programme for people with type 2 diabetes
administered by healthcare workers who have received special training.
BACKGROUND: The needs for diabetic care include increased training for healthcare
providers to enhance their confidence and skills in managing patients, both
physically and mentally. DESIGN: Quasi-experimental design. METHODS: This study
recruited participants from outpatient clinics in 10 hospitals in Taiwan. In
2010, purposive sampling was used to recruit 228 participants from two medical
centres, five regional hospitals and three district hospitals. Participants were
enrolled in a 'diabetes self-management programme' (watching patient videos,
reading a diabetes self-care handbook, participating in four consultation courses
of diabetes self-efficacy improvement, telephone follow-up and positive
reinforcement). Efficacy analysis of post-test diabetes outcome variables of the
experimental group was carried out. Sex, age and pretest score were used as the
control variables for ancova test. RESULTS: Patients in the experimental group
had significant improvement in body mass index (p < 0.01), waistline
circumference (p < 0.001), haemoglobin A1C levels (p < 0.001), degrees of anxiety
and depression (p < 0.001), self-efficacy (p < 0.001) and levels of self-care (p
< 0.001). CONCLUSION: Self-efficacy of people with diabetes can be effectively
improved by planned implementation of a 'diabetes self-management programme' by
trained healthcare workers. RELEVANCE TO CLINICAL PRACTICE: The diabetes care
professionals are provided the self-management programme to strengthen the
awareness and importance of self-management in diabetes care.
PMID- 24354788
TI - Epiregulin is critical for the acinar cell regeneration of the submandibular
gland in a mouse duct ligation model.
AB - Acinar cell regeneration from tubular structures has been reported to occur in
duct-deligated salivary glands. However, the detailed process of acinar cell
regeneration has not been clarified. We have developed a mouse duct ligation
model to clarify the mechanisms underlying acinar cell regeneration, and we
analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor
(EGF) ligands using the model. We studied these ligands expressions in the course
of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the
duct-ligated portion of the submandibular gland (SMG) that underwent atrophy,
newly formed acinar cells were observed arising from the tubular structures after
the release of the duct obstruction. The constitutive expression of EGFR was
observed by immunohistochemistry in both the duct-ligated and duct-deligated
animals as well as in normal controls. The EGFR phosphorylation detected on the
tubular structures after duct ligation paralleled the acinar cell regeneration.
RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from
day 0 to day 3 after the release of the duct obstruction. The EGF level was
increased only after day 7. In vitro, cultured cells isolated from ligated SMGs
proliferated and produced EGF ligands following the addition of epiregulin to the
culture medium. These findings suggest that the tubular structures localized in
an atrophic gland are the source of acinar cell regeneration of the salivary
gland. The induction of EGF ligands, in particular epiregulin, may play an
important role in acinar cell regeneration in this model.
PMID- 24354789
TI - An actin-like protein is involved in regulation of mitochondrial and flagellar
functions as well as in intramacrophage survival of Leishmania donovani.
AB - Actin-related proteins are ubiquitous actin-like proteins that show high
similarity with actin in terms of their amino acid sequence and three-dimensional
structure. However, in lower eukaryotes, such as trypanosomatids, their functions
have not yet been explored. Here, we show that a novel actin-related protein (ORF
LmjF.13.0950) is localized mainly in the Leishmania mitochondrion. We further
reveal that depletion of the intracellular levels of this protein leads to an
appreciable decrease in the mitochondrial membrane potential as well as in the
ATP production, which appears to be accompanied with impairment in the flagellum
assembly and motility. Additionally, we report that the mutants so generated fail
to survive inside the mouse peritoneal macrophages. These abnormalities are,
however, reversed by the episomal gene complementation. Our results, for the
first time indicate that apart from their classical roles in the cytoplasm and
nucleus, actin-related proteins may also regulate the mitochondrial function, and
in case of Leishmania donovani they may also serve as the essential factor for
their survival in the host cells.
PMID- 24354790
TI - Working to improve survival and health for babies born very preterm: the WISH
project protocol.
AB - BACKGROUND: Babies born very preterm (before 30 weeks gestation) are at high risk
of dying in their first weeks of life, and those who survive are at risk of
developing cerebral palsy in childhood. Recent high-quality evidence has shown
that giving women magnesium sulphate immediately prior to very early birth can
significantly increase the chances of their babies surviving free of cerebral
palsy. In 2010 Australian and New Zealand clinical practice guidelines
recommended this therapy. The WISH (Working to Improve Survival and Health for
babies born very preterm) Project aims to bi-nationally improve and monitor the
use of this therapy to reduce the risk of very preterm babies dying or having
cerebral palsy. METHODS/DESIGN: The WISH Project is a prospective cohort study.
The 25 Australian and New Zealand tertiary level maternity hospitals will be
provided with a package of active implementation strategies to guide the
introduction and local adaptation of guideline recommendations. Surveys will be
conducted at individual hospitals to evaluate outcomes related to local
implementation progress and the use and value of the WISH implementation
strategies. For the hospitals participating in the 'WISH audit of uptake and
health outcomes data collection', the primary health outcomes (assessed through
case note review, and 24 month corrected age questionnaires) will be: the
proportion of eligible women receiving antenatal magnesium sulphate; and rates of
death prior to primary hospital discharge and cerebral palsy at two years
corrected age in infants born to eligible mothers. For hospitals wishing to
assess factors influencing translation locally, barriers and facilitators will be
measured through interviews with health care professionals, to further guide
implementation strategies. Study outcomes for the early phase of the project
(Year 1) will be compared with the later intervention phase (Years 2 and 3).
DISCUSSION: The WISH Project will offer insight into the effectiveness of a
multifaceted implementation strategy to improve the uptake of a novel
neuroprotective therapy in obstetric clinical practice. The successful
implementation of antenatal magnesium sulphate for fetal neuroprotection in
Australia and New Zealand could lead to over 90 fewer very preterm babies dying
or suffering the long-term consequences of cerebral palsy each year.
PMID- 24354791
TI - Component-specific, cigarette particle deposition modeling in the human
respiratory tract.
AB - Inhalation of cigarette smoke particles (CSP) leads to adverse health effects in
smokers. Determination of the localized dose to the lung of the inhaled smoke
aids in determining vulnerable sites, and identifying components of the smoke
that may be responsible for the adverse effects; thus providing a roadmap for
harm reduction of cigarette smoking. A particle deposition model specific to CSP
was developed for the oral cavity and the lung by accounting for cigarette
particle size growth by hygroscopicity, phase change and coagulation. In
addition, since the cigarette puff enters the respiratory tract as a dense cloud,
the cloud effect on particle drag and deposition was accounted for in the
deposition model. Models of particle losses in the oral cavities were developed
during puff drawing and subsequent mouth-hold. Cigarette particles were found to
grow by hygroscopicity and coagulation, but to shrink as a result of nicotine
evaporation. The particle size reached a plateau beyond which any disturbances in
the environmental conditions caused the various mechanisms to balance each other
out and the particle size remain stable. Predicted particle deposition
considering the cloud effects was greater than when treated as a collection of
non-interacting particles (i.e. no cloud effects). Accounting for cloud movement
provided the necessary physical mechanism to explain the greater than expected,
experimentally observed and particle deposition. The deposition model for CSP can
provide the necessary input to determine the fate of inhaled CSP in the lung. The
knowledge of deposition will be helpful for health assessment and identification
and reduction of harmful components of CSP.
PMID- 24354792
TI - Biased signalling and proteinase-activated receptors (PARs): targeting
inflammatory disease.
AB - Although it has been known since the 1960s that trypsin and chymotrypsin can
mimic hormone action in tissues, it took until the 1990s to discover that serine
proteinases can regulate cells by cleaving and activating a unique four-member
family of GPCRs known as proteinase-activated receptors (PARs). PAR activation
involves the proteolytic exposure of its N-terminal receptor sequence that folds
back to function as a 'tethered' receptor-activating ligand (TL). A key N
terminal arginine in each of PARs 1 to 4 has been singled out as a target for
cleavage by thrombin (PARs 1, 3 and 4), trypsin (PARs 2 and 4) or other proteases
to unmask the TL that activates signalling via Gq , Gi or G12 /13 . Similarly,
synthetic receptor-activating peptides, corresponding to the exposed 'TL
sequences' (e.g. SFLLRN-, for PAR1 or SLIGRL- for PAR2) can, like proteinase
activation, also drive signalling via Gq , Gi and G12 /13 , without requiring
receptor cleavage. Recent data show, however, that distinct proteinase-revealed
'non-canonical' PAR tethered-ligand sequences and PAR-activating agonist and
antagonist peptide analogues can induce 'biased' PAR signalling, for example, via
G12 /13 -MAPKinase instead of Gq -calcium. This overview summarizes implications
of this 'biased' signalling by PAR agonists and antagonists for the recognized
roles the PARs play in inflammatory settings.
PMID- 24354793
TI - IgG-mediated down-regulation of IgE bound to mast cells: a potential novel
mechanism of allergen-specific desensitization.
AB - BACKGROUND: Allergen-specific IgGs are known to inhibit IgE-mediated mast cell
degranulation by two mechanisms, allergen-neutralization and engagement of the
inhibitory FcgammaRIIB recruiting the phosphatase SHIP-1. Here we unravel an
additional mechanism of IgG-mediated mast cell desensitization in mice: down
regulation of allergen-specific IgE. METHODS: Mast cells were loaded in vitro and
in vivo with monoclonal IgE antibodies specific for Fel d1 and exposed to immune
complexes consisting of Fel d1-specific IgG antibodies recognizing different
epitopes. Down regulation of IgE was followed by flow cytometry. RESULTS: Mast
cells loaded with 2 different IgE antibodies efficiently internalized the IgE
antibodies if exposed to recombinant Feld d1. In contrast, no down-regulation
occurred if mast cells were loaded with IgE antibodies exhibiting a single
specificity before stimulation with recombinant Fel d1 [corrected].
Interestingly, however, IgEs of a single specificity were rapidly down-regulated
in vitro and in vivo in the presence of Fel d1-specific monoclonal IgGs
recognizing another epitope on Fel d1. Despite FceRI-internalization, little
calcium flux or mast cell degranulation occurred. FcgammaRIIB played a dual role
in the process since it enhanced IgE internalization and prevented cellular
activation as documented by the inhibited calcium flux and mast cell
degranulation. Similar observations were made in the presence of low
concentrations of IgEs recognizing several epitopes on Fel d1. CONCLUSION: We
demonstrate here that Fel d1-specific IgG antibodies interact with FcgammaRIIB
which (i) promotes IgE internalization; and (ii) inhibits mast cell activation.
These results broaden our understanding of allergen-specific desensitization and
may provide a mechanism for long-term desensitization of mast cells by selective
removal of long-lived IgE antibodies on mast cells.
PMID- 24354794
TI - Prevalence and characteristics of depressive disorders in type 1 diabetes.
AB - BACKGROUND: Persons with diabetes and depression have increased risk of
complications and increased mortality. We aimed to investigate the prevalence,
clinical characteristics and impact with regard to glycosylated haemoglobin
(HbA1c) of depressive disorders in persons with type 1 diabetes at an outpatient
specialist diabetes clinic. FINDINGS: A total of 51 persons with type 1 diabetes
were diagnosed according to Mini International Neuropsychiatric Interview
(M.I.N.I) with regard to dysthymia and previous or ongoing depressive episodes
during spring 2005. HbA1c was measured at the day of the interview, and self
reported information on family history of depressive disorders was obtained.
Eight persons (16%; 95% CI: 7%, 29%) were in the midst of a major depressive
episode, 4 of these also reported a previous episode of depression. Seven of the
8 persons with an ongoing major depressive episode met the criteria for
melancholia. Three persons (6%) met the criteria for dysthymia, and 6 persons
(12%) had previous episode(s) of depression, without being currently depressed.
The 17 (33%; 95% CI: 21%, 48%) persons with ongoing and/or previous depressive
disorder had increased HbA1c (8.5%; 95% CI: 7.6%, 9.4%) compared to those without
depressive disorders (7.9%; 95% CI: 7.5%, 8.3%), although the difference did not
reach statistical significance. CONCLUSIONS: Persons with type 1 diabetes had a
high prevalence of depressive disorders, mainly depressive episodes that also met
the criteria for melancholia, a subtype often considered a more serious and
"biologic" form of depression. We were not able to demonstrate that persons with
depressive disorders had poorer regulated diabetes compared to those without
depressive disorders.
PMID- 24354795
TI - Effect of cerebral circulatory arrest on cerebral near-infrared spectroscopy in
pediatric patients.
AB - BACKGROUND/AIMS: The aim was to investigate whether cerebral transcutaneous near
infrared spectroscopy (NIRS) or two-site NIRS is a suitable monitoring tool to
detect or confirm a cerebral circulatory arrest in pediatric intensive care unit
(PICU) patients. METHODS: Prospective single-center pediatric observational
study. Simultaneous NIRS measurements over forehead (cNIRS, crS02) and kidney
(rNIRS, rrSO2), at the same time, the cardiac output were determined by
transthoracic echocardiography. Area under the curve (AUC) in the receiver
operating curve (ROC) was analyzed for NIRS regarding cerebral circulatory
arrest. RESULTS: There were two groups of patients (weight 2.1-73 kg): Group A:
patients with intact cerebral perfusion (n = 36). Group B: patients with cerebral
circulatory arrest (n = 8) proven by Doppler ultrasound scan or perfusion
scintigraphy. There was no difference in cardiac output between the groups. PICU
mortality for Group A was 3/36 (8.3%), for Group B 8/8, (100%). Mean cNIRS values
were significantly higher with 68.92 (SEM = 2.54, SD = 15.25) in Group A compared
with 34.63 (SEM = 5.36, SD = 15.15) in Group B (P < 0.001). ROC analysis for
cNIRS detecting cerebral circulatory arrest was significant (AUC 0.948, 95%
confidence interval 0.876-1.000, SE = 0.037, P < 0.001). Discrimination was
optimal at 46 for cNIRS, at 36.5 for the difference rNIRS-cNIRS and at 0.5646 for
the quotient cNIRS/rNIRS. The probability of a cerebral circulatory arrest was
77.8% (cNIRS) and 87.5% (combinations of cNIRS and rNIRS) at these cutoffs.
CONCLUSIONS: cNIRS did detect cerebral circulatory arrest with high sensitivity.
Specificity was, however, not high enough to confirm a cerebral circulatory
arrest.
PMID- 24354798
TI - Effects of hydrogen peroxide on mucociliary transport in human airway epithelial
cells.
AB - The effects of environmental pollutants on airway clearance have not been well
elucidated. This study examined mucociliary transport using different sized
fluorescent particles on polarized human airway epithelial cells which were
maintained in an air-liquid interface (ALI) culture system. The effects of
hydrogen peroxide (H2O2) exposure on mucociliary transport were also
investigated. The movement of fluorescent particles with diameters of 10-14 and
2.5-4.5 um was observed by fluorescent microscopy as an index of the mucociliary
transport. The mixture of the particles with two different sizes was propelled
concentrically on the apical surface by the interaction of ciliary activity and
mucus in the control condition, whereas H2O2 exposure for 24 h significantly
inhibited the movement of the particles. The particle sizes did not affect their
movement after the control or H2O2 exposure. These results suggest that particle
tracking on polarized human airway epithelial cells is a useful experimental tool
for the evaluation of the effect of environmental pollutants on mucociliary
transport. In addition, reactive oxygen species may impair mucociliary transport,
leading to the airway damage and exacerbation of respiratory diseases.
PMID- 24354797
TI - Expression of insulin-like growth factor-1 receptor in metastatic uveal melanoma
and implications for potential autocrine and paracrine tumor cell growth.
AB - We investigated the importance of the insulin-like growth factor-1 receptor (IGF
1R) in hepatic metastases of uveal melanoma. The expression pattern of IGF-1R in
archival tissue samples of hepatic metastasis from 24 patients was analyzed by
immunohistochemistry. All the samples of hepatic metastases stained positive for
IGF-1R. To investigate the biological role of IGF-1R on the growth of metastatic
uveal melanoma, a long-term cell line obtained from a hepatic metastasis (TJU
UM001) was evaluated. TJU-UM001 expressed cell surface IGF-1R (>90%) and
proliferated in response to exogenous and endogenous insulin-like growth factor-1
(IGF-1). Correlatively, anti-IGF-1R antibody completely blocked IGF-1-induced
growth of TJU-UM001 cells. IGF-1 preferentially induced phosphorylation of Akt
(S473) in quiescent TJU-UM001 cells, and this was blocked by anti-IGF-1R
antibody. This study suggests that autocrine and paracrine mechanisms underlie
IGF-1-induced growth of metastatic uveal melanoma and underscore the potential
benefit of IGF-1 or IGF-1R antagonism in treatment for metastatic uveal melanoma.
PMID- 24354799
TI - "Out-gel" tryptic digestion procedure for chemical cross-linking studies with
mass spectrometric detection.
AB - SDS-PAGE is one of the most powerful protein separation techniques, and in-gel
digestion is the leading method for converting proteins separated by SDS-PAGE
into peptides suitable for mass spectrometry-based proteomic studies. In in-gel
digestion, proteins are digested within the gel matrix, and the resulting
peptides are extracted into an appropriate buffer. Transfer of the digested
peptides to the liquid phase for subsequent mass spectrometric analysis, however,
may be hampered by peptide-specific characteristics, including size, shape, poor
solubility, adsorption to the polyacrylamide, and-in the case of cross-linking
applications-by the branched structure of the peptides produced. This can be a
limitation in cross-linking studies where efficient recoveries of the cross
linked peptides are critical. To overcome this limitation, we have developed a
modification to the standard in-gel digestion procedure for SDS-PAGE-separated
cross-linked proteins, based on older passive diffusion methods. By omitting the
gel staining and gel fixation steps, intact proteins or cross-linked protein
complexes can move through the gel and into the buffer solution. Digestion of the
entire protein in the buffer outside the gel increases the probability that most
of the proteolytic peptides produced will be present in the final digest
solution. The resulting peptide mixture is then freed of SDS and concentrated
using SCX (strong cation exchange) zip-tips and analyzed by mass spectrometry.
For standard protein identification studies and the recovery of noncross-linked
peptides, the in-gel procedure outperformed the out-gel procedure, but for cross
linking studies with enrichable cross-linkers (such as CBDPS), the standard out
gel procedure allowed the recoveries of cross-links not recovered via the in-gel
method. Labeling experiments showed that, with an enrichable cross-linker, 93% of
the cross-links showed better or equal recoveries with the out-gel procedure, as
compared to the in-gel procedure. It should be noted that this method is not
designed to replace in-gel digestion for most proteomics applications. However,
by using the out-gel method, we were able to detect twice as many interprotein
CBDPS cross-links from the histone H2A/H2B complex as were found in the in-gel
digested sample.
PMID- 24354796
TI - Pharmacogenomics in psychiatry: the relevance of receptor and transporter
polymorphisms.
AB - The treatment of severe mental illness, and of psychiatric disorders in general,
is limited in its efficacy and tolerability. There appear to be substantial
interindividual differences in response to psychiatric drug treatments that are
generally far greater than the differences between individual drugs; likewise,
the occurrence of adverse effects also varies profoundly between individuals.
These differences are thought to reflect, at least in part, genetic variability.
The action of psychiatric drugs primarily involves effects on synaptic
neurotransmission; the genes for neurotransmitter receptors and transporters have
provided strong candidates in pharmacogenetic research in psychiatry. This paper
reviews some aspects of the pharmacogenetics of neurotransmitter receptors and
transporters in the treatment of psychiatric disorders. A focus on serotonin,
catecholamines and amino acid transmitter systems reflects the direction of
research efforts, while relevant results from some genome-wide association
studies are also presented. There are many inconsistencies, particularly between
candidate gene and genome-wide association studies. However, some consistency is
seen in candidate gene studies supporting established pharmacological mechanisms
of antipsychotic and antidepressant response with associations of functional
genetic polymorphisms in, respectively, the dopamine D2 receptor and serotonin
transporter and receptors. More recently identified effects of genes related to
amino acid neurotransmission on the outcome of treatment of schizophrenia,
bipolar illness or depression reflect the growing understanding of the roles of
glutamate and gamma-aminobutyric acid dysfunction in severe mental illness. A
complete understanding of psychiatric pharmacogenomics will also need to take
into account epigenetic factors, such as DNA methylation, that influence
individual responses to drugs.
PMID- 24354800
TI - Critical stoichiometric ratio of CD4(+) CD25(+) FoxP3(+) regulatory T cells and
CD4(+) CD25(-) responder T cells influence immunosuppression in patients with B
cell acute lymphoblastic leukaemia.
AB - Regulatory T (Treg) cells act to suppress activation of the immune system and
thereby maintain immunological homeostasis and tolerance to self-antigens. The
frequency and suppressing activity of Treg cells in general are high in different
malignancies. We wanted to identify the role and regulation of CD4(+) CD25(+)
FoxP3(+) Treg cells in B-cell acute lymphoblastic leukaemia (B-ALL). We have
included patients at diagnosis (n = 54), patients in clinical remission (n = 32)
and normal healthy individuals (n = 35). These diagnosed patients demonstrated a
lower number of CD4(+) CD25(+) cells co-expressing a higher level of FoxP3,
interleukin-10, transforming growth factor-beta and CD152/CTLA-4 than the normal
population. Treg cells from patients showed a higher suppressive capability on
CD4(+) CD25(-) responder T (Tresp) cells than normal. The frequency and
immunosuppressive potential of CD4(+) CD25(+) FoxP3(+) Treg cells became high
with the progression of malignancy in B-ALL. Relative distribution of Tresp and
Treg cells was only ~5 : 1 in B-ALL but ~35 : 1 in normal healthy individuals,
further confirming the elevated immunosuppression in patients. A co-culture study
at these definite ex vivo ratios, indicated that Treg cells from B-ALL patients
exhibited higher immunosuppression than Treg cells from normal healthy
individuals. After chemotherapy using the MCP841 protocol, the frequency of
CD4(+) CD25(+) cells was gradually enhanced with the reduction of FoxP3,
interleukin-10 positivity corresponded with disease presentation, indicating
reduced immunosuppression. Taken together, our study indicated that the CD4(+)
CD25(+) FoxP3(+) Treg cells played an important role in immunosuppression,
resulting in a positive disease-correlation in these patients. To the best of our
knowledge, this is the first detailed report on the frequency, regulation and
functionality of Treg cells in B-ALL.
PMID- 24354801
TI - The effects of fasting in Muslim patients taking warfarin.
AB - BACKGROUND: Anticoagulation with warfarin is influenced by dietary changes but
the effect of fasting on warfarin therapy is unknown. OBJECTIVES: To study
changes in international normalized ratio (INR) and the percentage of time within
therapeutic range (%TTR) before, during and after the Muslim fasting month
(Ramadan) in stable warfarinised Muslim patients. METHODS/PATIENTS: In this
prospective study, weekly INR readings were taken at home visits from
participating patients during three study periods: before, during and after
Ramadan. Readings were blinded to patients and their primary physicians except
for when pre-set study endpoints were reached. RESULTS: Among 32 participating
patients, mean INR increased by 0.23 (P = 0.006) during Ramadan from the pre
Ramadan month and decreased by 0.28 (P < 0.001) after Ramadan. There was no
significant difference (P = 1.000) in mean INR between the non-Ramadan months.
%TTR declined from 80.99% before Ramadan to 69.56% during Ramadan (P = 0.453).
The first out-of-range INR was seen around 12.1 days (95% CI, 9.0-15.1) after the
start of fasting and returned to range at about 10.8 days (95% CI, 7.9-13.7)
after Ramadan. Time above range increased from 10.80% pre-Ramadan to 29.87%
during Ramadan (P = 0.027), while time below range increased from 0.57% during
Ramadan to 15.49% post-Ramadan (P = 0.006). No bleeding or thrombotic events were
recorded. CONCLUSIONS: Fasting significantly increases the mean INR of medically
stable patients taking warfarin and the likelihood of having an INR above
therapeutic targets. For patients maintained at the higher end of INR target
ranges or at increased risk of bleeding, closer monitoring or dosage adjustment
may be necessary during fasting.
PMID- 24354802
TI - Acylated ghrelin and leptin concentrations in patients with type 2 diabetes
mellitus, people with prediabetes and first degree relatives of patients with
diabetes, a comparative study.
AB - BACKGROUND: Ghrelin is known as a new endocrine component supposed to have an
influence in control of feeding behavior and energy balance. Recent studies have
shown that ghrelin concentration in the subjects with diabetes mellitus type 2
(DM 2) is lower than normal. To clarify the relationship between ghrelin and
insulin resistance and also DM 2, a cross-sectional study was designed. METHODS:
In a cross-sectional study, 87 subjects were enrolled in three groups, 29 with
DM2, 29 pre-diabetes state and 29 normoglycemic subjects of first-degree
relatives of diabetic group. After clinical examination, blood samples were taken
to measure fasting blood glucose, HbA1c, lipids, insulin, leptin and acylated
ghrelin concentrations. RESULTS: Mean serum concentrations of acylated ghrelin in
all groups (47.4 +/- 27.9 pg/ml) were lower than normal values (150.3 +/- 56.4
pg/ml) (P: 0.006) without significant difference within groups comparison(P:
0.1). A significant correlation was found between ghrelin concentration with body
mass index (BMI) (r: -0.23, p <0.02) and abdominal circumference (AC) (r: -0.28,
P < 0.008). Also inverse relationship between ghrelin level and insulin
resistance (HOMA-IR) (r: -.032, p: 0.002) was seen in all subjects. Leptin level
has a significant correlation with abdominal circumference (AC) and BMI (P <
0.0001) but not with ghrelin. CONCLUSION: This study showed that obesity has a
strong association with the reduced level of ghrelin concentration. It seems that
the process of ghrelin reduction is initiated in earlier stages of insulin
resistance prior to the onset of overt DM.
PMID- 24354803
TI - Framing the patent troll debate.
AB - The patent troll debate has reached a fevered pitch in the USA. This editorial
seeks to frame the debate by pointing out the lack of clarity in defining patent
trolls and their allegedly harmful actions. It then frames the debate by asking
currently unanswered questions: Where do troll patents come from? What are the
effects of troll assertions? Will policy changes improve the system?
PMID- 24354804
TI - Commentary on Manfredini et al.
PMID- 24354806
TI - Hair graying and loss induced by imatinib mesylate.
PMID- 24354805
TI - Reduced annexin A6 expression promotes the degradation of activated epidermal
growth factor receptor and sensitizes invasive breast cancer cells to EGFR
targeted tyrosine kinase inhibitors.
AB - BACKGROUND: The expression of annexin A6 (AnxA6) in AnxA6-deficient non-invasive
tumor cells has been shown to terminate epidermal growth factor receptor (EGFR)
activation and downstream signaling. However, as a scaffolding protein, AnxA6 may
stabilize activated cell-surface receptors to promote cellular processes such as
tumor cell motility and invasiveness. In this study, we investigated the
contribution of AnxA6 in the activity of EGFR in invasive breast cancer cells and
examined whether the expression status of AnxA6 influences the response of these
cells to EGFR-targeted tyrosine kinase inhibitors (TKIs) and/or patient survival.
RESULTS: We demonstrate that in invasive BT-549 breast cancer cells AnxA6
expression is required for sustained membrane localization of activated (phosho
Y1068) EGFR and consequently, persistent activation of MAP kinase ERK1/2 and
phosphoinositide 3-kinase/Akt pathways. Depletion of AnxA6 in these cells was
accompanied by rapid degradation of activated EGFR, attenuated downstream
signaling and as expected enhanced anchorage-independent growth. Besides
inhibition of cell motility and invasiveness, AnxA6-depleted cells were also more
sensitive to the EGFR-targeted TKIs lapatinib and PD153035. We also provide
evidence suggesting that reduced AnxA6 expression is associated with a better
relapse-free survival but poorer distant metastasis-free and overall survival of
basal-like breast cancer patients. CONCLUSIONS: Together this demonstrates that
the rapid degradation of activated EGFR in AnxA6-depleted invasive tumor cells
underlies their sensitivity to EGFR-targeted TKIs and reduced motility. These
data also suggest that AnxA6 expression status may be useful for the prediction
of the survival and likelihood of basal-like breast cancer patients to respond to
EGFR-targeted therapies.
PMID- 24354807
TI - Lateral nasal osteotomy: a comparative study between the use of osteotome and a
diamond surgical burr - a cadaver study.
AB - BACKGROUND: The ultimate goal of rhinoplasty is to achieve a controllable,
reliable and an aesthetically pleasing result. Various approaches and instruments
have been introduced for the correction of the bony walls of the nose to improve
predictability of the procedure and to minimize the associated trauma. We
conducted a cadaveric study comparing the results of osteotomy of the nasal wall
using a diamond surgical burr with those using a 2-mm osteotome. MATERIAL AND
METHODS: Bilateral osteotomy of the nasal wall was performed on 10 cadavers. The
20 lateral nasal osteotomies were carried out on 7 females and 3 males of an age
range between 61-91 years. A 2-mm osteotome was used percutaneously to perforate
the lateral nasal wall of the right side. On the left side a 2-mm diamond
surgical burr was introduced via an intraoral approach to thin out the lateral
nasal wall. The in-fracture of the nasal bone was accomplished by controlled
finger pressure. The nasal mucosa was inspected endoscopically and also dissected
to identify any perforations or lacerations. The pattern of nasal fracture and
the presence of any fragmentation of the bony segments were assessed clinically.
RESULTS: The in-fracturing of the nasal bone was accomplished by gentle pressure
on the left side, but required more force on the contra lateral side. On the left
side the in-fractured lateral nasal wall remained as one piece and no
irregularities were seen. On the right side 3-5 bony fragments of irregular sizes
and shapes were detected. There were 3-4 tears of the nasal mucosa, where the
osteotome was applied. However, no mucosal tears were detected at the side, where
the surgical burr was used. CONCLUSION: Osteotomy of the lateral nasal wall with
a diamond burr via intraoral approach is more precise and associated with fewer
complications in comparison with the use of the osteotome.
PMID- 24354808
TI - Gold nanostars for superficial diseases: a promising tool for localized
hyperthermia?
PMID- 24354809
TI - Biological effects of Tat cell-penetrating peptide: a multifunctional Trojan
horse?
PMID- 24354810
TI - Star-shaped block polymers as a molecular biomaterial for nanomedicine
development.
PMID- 24354812
TI - Research highlights: Highlights from the last year in nanomedicine.
PMID- 24354813
TI - Lipid-based nanoparticles in the systemic delivery of siRNA.
AB - RNAi therapeutics are believed to be the future of personalized medicine and have
shown promise in early clinical trials. However, many physiological barriers
exist in the systemic delivery of siRNAs to the cytoplasm of targeted cells to
perform their function. To overcome these barriers, many siRNA delivery systems
have been developed. Among these, lipid-based nanoparticles have great potential
owing to their biocompatibility and low toxicity in comparison with inorganic
nanoparticles and viral systems. This review discusses the hurdles of systemic
siRNA delivery and highlights the recent progress made in lipid-based
nanoparticles, which are categorized based on their key lipid components,
including cationic lipid, lipoprotein, lipidoid, neutral lipid and anionic lipid
based nanoparticles. It is expected that these lipid nanoparticle-based siRNA
delivery systems will have an enabling role for personalized cancer medicine,
where siRNA delivery will join forces with genetic profiling of individual
patients to achieve the best treatment outcome.
PMID- 24354815
TI - Surface modification of nonviral nanocarriers for enhanced gene delivery.
AB - Biomedical nanotechnology has given a new lease of life to gene therapy with the
ever-developing and ever-diversifying nonviral gene delivery nanocarriers. These
are designed to pass a series of barriers in order to bring their nucleic acid
cargo to the right subcellular location of particular cells. For a given
application, each barrier has its dedicated strategy, which translates into a
physicochemical, biological and temporal identity of the nanocarrier surface.
Different strategies have thus been explored to implement adequate surface
identities on nanocarriers over time for systemic delivery. In that context, this
review will mainly focus on organic nanocarriers, for which these strategies will
be described and discussed.
PMID- 24354816
TI - One-dimensional nanoprobes for single-cell studies.
AB - Owing to variation of individual cells within a population, single-cell studies
are of great interest to researchers. Recent developments in nanofabrication
technology have made this area increasingly attractive as one-dimensional (1D)
nanoscale probes can be manufactured with increasing accuracy. Here, we provide
an overview and description of the major designs that have been reported to date.
For more details of what applications could be realized and how, based on the
probe shapes and designs, we summarize the most recently reported performances of
1D single-cell probes with their advantages and limitations. Minimally invasive
probes are required for long-term experiments on single cells. Carbon nanotubes
with their unique properties and structure are excellent candidates for multitask
robotic intracellular probes. Carbon nanotube-tipped cellular endoscopes are less
invasive compared with pipettes or cantilever tips. Advances in nanofabrication
techniques have made it possible to produce more consistent nanoscale cellular
probes that can capture a variety of information from optical, electrical and
chemical signals. In addition, these tools can transfer tiny amounts of fluids
and molecular materials in a highly localized fashion for the purpose of
analyzing or stimulating a variety of responses at the level of individual cells
and even cellular organelles. We conclude with a critical analysis of the current
state of the field as well as the major obstacles for further probe development
of minimally invasive probes and their widespread use in cell biology.
PMID- 24354814
TI - Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey
of nanoparticles.
AB - Recent advances in nanoparticle technology have enabled the fabrication of
nanoparticle classes with unique sizes, shapes and materials, which in turn has
facilitated major advancements in the field of nanomedicine. More specifically,
in the last decade, nanoscientists have recognized that nanomedicine exhibits a
highly engineerable nature that makes it a mainstream scientific discipline that
is governed by its own distinctive principles in terms of interactions with cells
and intravascular, transvascular and interstitial transport. This review focuses
on the recent developments and understanding of the relationship between the
shape of a nanoparticle and its navigation through different biological
processes. It also seeks to illustrate that the shape of a nanoparticle can
govern its in vivo journey and destination, dictating its biodistribution,
intravascular and transvascular transport, and, ultimately, targeting of
difficult to reach cancer sites.
PMID- 24354817
TI - Improving maternal health in Pakistan: toward a deeper understanding of the
social determinants of poor women's access to maternal health services.
AB - Evidence suggests national- and community-level interventions are not reaching
women living at the economic and social margins of society in Pakistan. We
conducted a 10-month qualitative study (May 2010-February 2011) in a village in
Punjab, Pakistan. Data were collected using 94 in-depth interviews, 11 focus
group discussions, 134 observational sessions, and 5 maternal death case studies.
Despite awareness of birth complications and treatment options, poverty and
dependence on richer, higher-caste people for cash transfers or loans prevented
women from accessing required care. There is a need to end the invisibility of
low-caste groups in Pakistani health care policy. Technical improvements in
maternal health care services should be supported to counter social and economic
marginalization so progress can be made toward Millennium Development Goal 5 in
Pakistan.
PMID- 24354819
TI - Shifts in intended and unintended pregnancies in the United States, 2001-2008.
AB - OBJECTIVES: We monitored trends in pregnancy by intendedness and outcomes of
unintended pregnancies nationally and for key subgroups between 2001 and 2008.
METHODS: Data on pregnancy intentions from the National Survey of Family Growth
(NSFG) and a nationally representative survey of abortion patients were combined
with counts of births (from the National Center for Health Statistics), counts of
abortions (from a census of abortion providers), estimates of miscarriages (from
the NSFG), and population denominators from the US Census Bureau to obtain
pregnancy rates by intendedness. RESULTS: In 2008, 51% of pregnancies in the
United States were unintended, and the unintended pregnancy rate was 54 per 1000
women ages 15 to 44 years. Between 2001 and 2008, intended pregnancies decreased
and unintended pregnancies increased, a shift previously unobserved. Large
disparities in unintended pregnancy by relationship status, income, and education
increased; the percentage of unintended pregnancies ending in abortion decreased;
and the rate of unintended pregnancies ending in birth increased, reaching 27 per
1000 women. CONCLUSIONS: Reducing unintended pregnancy likely requires addressing
fundamental socioeconomic inequities, as well as increasing contraceptive use and
the uptake of highly effective methods.
PMID- 24354818
TI - Association between birthplace and current asthma: the role of environment and
acculturation.
AB - OBJECTIVES: We evaluated associations between current asthma and birthplace among
major racial/ethnic groups in the United States. METHODS: We used multivariate
logistic regression methods to analyze data on 102,524 children and adolescents
and 255,156 adults in the National Health Interview Survey (2001-2009). RESULTS:
We found significantly higher prevalence (P < .05) of current asthma among
children and adolescents (9.3% vs 5.1%) and adults (7.6% vs 4.7%) born in the 50
states and Washington, DC (US-born), than among those born elsewhere. These
differences were among all age groups of non-Hispanic Whites, non-Hispanic
Blacks, and Hispanics (excluding Puerto Ricans) and among Chinese adults. Non-US
born adults with 10 or more years of residency in the United States had higher
odds of current asthma (odds ratio = 1.55; 95% confidence interval = 1.25, 1.93)
than did those who arrived more recently. Findings suggested a similar trend
among non-US-born children. CONCLUSIONS: Current asthma status was positively
associated with being born in the United States and with duration of residency in
the United States. Among other contributing factors, changes in environment and
acculturation may explain some of the differences in asthma prevalence.
PMID- 24354820
TI - Effect of maternal-child home visitation on pregnancy spacing for first-time
Latina mothers.
AB - OBJECTIVES: We examined the impact of a maternal-child home visitation program on
birth spacing for first-time Latina mothers, focusing on adolescents and women
who identified as Mexican or Puerto Rican. METHODS: This was a retrospective
cohort study. One thousand Latina women enrolled in the Pennsylvania Nurse-Family
Partnership between January 1, 2003, and December 31, 2007, were matched to
nonenrolled Latina women using propensity scores. The primary outcome was the
time to second pregnancy that resulted in a live birth (interpregnancy interval).
Proportional hazards models and bootstrap methods compared the time to event.
RESULTS: Home visitation was associated with a small decrease in the risk of a
short interpregnancy interval (<= 18 months) among Latina women (hazards ratio
[HR] = 0.86; 95% confidence interval [CI] = 0.75, 0.99). This effect was driven
by outcomes among younger adolescent women (HR = 0.80; 95% CI = 0.65, 0.96).
There was also a trend toward significance for women of Mexican heritage (HR =
0.74; 95% CI = 0.49, 1.07), although this effect might be attributed to
individual agency performance. CONCLUSIONS: Home visitation using the Nurse
Family Partnership model had measurable effects on birth spacing in Latina women.
PMID- 24354821
TI - Use of spatial epidemiology and hot spot analysis to target women eligible for
prenatal women, infants, and children services.
AB - OBJECTIVES: We used a geographic information system and cluster analyses to
determine locations in need of enhanced Special Supplemental Nutrition Program
for Women, Infants, and Children (WIC) Program services. METHODS: We linked
documented births in the 2010 California Birth Statistical Master File with the
2010 data from the WIC Integrated Statewide Information System. Analyses focused
on the density of pregnant women who were eligible for but not receiving WIC
services in California's 7049 census tracts. We used incremental spatial
autocorrelation and hot spot analyses to identify clusters of WIC-eligible
nonparticipants. RESULTS: We detected clusters of census tracts with higher-than
expected densities, compared with the state mean density of WIC-eligible
nonparticipants, in 21 of 58 (36.2%) California counties (P < .05). In subsequent
county-level analyses, we located neighborhood-level clusters of higher-than
expected densities of eligible nonparticipants in Sacramento, San Francisco,
Fresno, and Los Angeles Counties (P < .05). CONCLUSIONS: Hot spot analyses
provided a rigorous and objective approach to determine the locations of
statistically significant clusters of WIC-eligible nonparticipants. Results
helped inform WIC program and funding decisions, including the opening of new WIC
centers, and offered a novel approach for targeting public health services.
PMID- 24354823
TI - Impact of Arizona's SB 1070 immigration law on utilization of health care and
public assistance among Mexican-origin adolescent mothers and their mother
figures.
AB - OBJECTIVES: We examined the impact of Arizona's "Supporting Our Law Enforcement
and Safe Neighborhoods Act" (SB 1070, enacted July 29, 2010) on the utilization
of preventive health care and public assistance among Mexican-origin families.
METHODS: Data came from 142 adolescent mothers and 137 mother figures who
participated in a quasi-experimental, ongoing longitudinal study of the health
and development of Mexican-origin adolescent mothers and their infants (4 waves;
March 2007-December 2011). We used general estimating equations to determine
whether utilization of preventive health care and public assistance differed
before versus after SB 1070's enactment. RESULTS: Adolescents reported declines
in use of public assistance and were less likely to take their baby to the
doctor; compared with older adolescents, younger adolescents were less likely to
use preventive health care after SB 1070. Mother figures were less likely to use
public assistance after SB 1070 if they were born in the United States and if
their post-SB 1070 interview was closer to the law's enactment. CONCLUSIONS:
Findings suggest that immigration policies such as SB 1070 may contribute to
decreases in use of preventive health care and public assistance among high-risk
populations.
PMID- 24354824
TI - A quasi-experimental analysis of maternal altitude exposure and infant birth
weight.
AB - OBJECTIVES: We analyzed singleton births to determine the relationship between
birth weight and altitude exposure. METHODS: We analyzed 715,213 singleton births
across 74 counties from the western states of Arizona, California, Colorado,
Idaho, Montana, Nevada, New Mexico, Oregon, Utah, and Washington from January 1,
2000, to December 31, 2000. Birth data were obtained from the Division of Vital
Statistics, National Center for Health Statistics, for registered births.
RESULTS: Regression analyses supported previous research by showing that a 1000
meter increase in maternal altitude exposure in pregnancy was associated with a
75.9-gram reduction in birth weight (95% confidence interval = -84.1, -67.6).
Quantile regression models indicated significant and near-uniform depressant
effects from altitude exposure across the conditional distribution of birth
weight. Bivariate sample-selection models showed that a 1000-meter increase in
altitude exposure, over and above baseline residential altitude, decreased birth
weight by an additional 58.8 grams (95% confidence interval = -98.4, -19.2).
CONCLUSIONS: Because of calculable health care-related costs associated with
lower birth weight, our reported results might be of interest to clinicians
practicing at higher altitudes.
PMID- 24354825
TI - Association of prenatal participation in a public health nutrition program with
healthy infant weight gain.
AB - OBJECTIVES: We tested the hypothesis that early enrollment in the Special
Supplemental Nutrition Program for Women, Infants and Children (WIC) is
associated with a reduced risk of rapid infant weight gain (RIWG). METHODS: We
used a longitudinal cohort of mother-infant pairs (n = 157,590) enrolled in WIC
in New York State from 2008 to 2009 and estimated the odds of RIWG, defined as a
12-month change in weight-for-age z score of more than .67, comparing infants of
mothers enrolled during the first, second, or third trimester of pregnancy with
those who delayed enrollment until the postpartum period. RESULTS: After
adjusting for potential confounders, the odds of RIWG (odds ratio [OR] = 0.76;
95% confidence interval [CI] = 0.74, 0.79) were significantly lower for infants
of women enrolling during the first trimester versus postpartum. Birth weight-for
gestational-age z score (OR = 0.33; 95% CI = 0.32, 0.33) attenuated the estimate
of prenatal versus postpartum enrollment (OR = 0.92; 95% CI = 0.88, 0.95; first
trimester enrollees). CONCLUSIONS: The results demonstrate that prenatal WIC
participation is associated with reduced risk of RIWG between birth and age 1
year. Improved birth weight for gestational age may be the mechanism through
which early prenatal WIC enrollment protects against RIWG.
PMID- 24354826
TI - Moving toward evidence-based federal Healthy Start program evaluations:
accounting for bias in birth outcomes studies.
AB - We used administrative and screening data from 2009 to 2010 to determine if
Healthy Start (HS), an enhanced prenatal services program, is reaching the most
vulnerable African American women in Kent County, Michigan. Women in HS are at
higher risk of key predictors of birth outcomes compared with other women. To
advance toward evidence-based HS program evaluations in the absence of randomized
controlled trials, future studies using comparison groups need to appropriately
establish baseline equivalence on a variety of risk factors related to birth
outcomes.
PMID- 24354827
TI - Construction of early and midlife work trajectories in women and their
association with birth weight.
AB - OBJECTIVES: We derived trajectories of the substantive complexity (SC) of work
across mid-adult life in women and determined their association with term birth
weight. SC is a concept that encompasses decision latitude, active learning, and
ability to use and expand one's abilities at work. METHODS: Using occupational
data from the National Longitudinal Survey of Youth 1979 and O*NET work
variables, we used growth mixture modeling (GMM) to construct longitudinal
trajectories of work SC from the ages of 18 to 34 years. The association between
work trajectories and birth weight of infants born to study participants was
modeled using generalized estimating equations, adjusting for education, income,
and relevant covariates. RESULTS: GMM yielded a 5-class solution for work
trajectories in women. Higher work trajectories were associated with higher term
birth weight and were robust to the inclusion of both education and income. A
work trajectory that showed a sharp rise after age 24 years was associated with
marked improvement in birth weight. CONCLUSIONS: Longitudinal modeling of work
characteristics might improve capacity to integrate occupation into a life-course
model that examines antecedents and consequences for maternal and child health.
PMID- 24354828
TI - The public health impact of training physicians to become obstetricians and
gynecologists in Ghana.
AB - OBJECTIVES: We assessed the public health effect of creating and sustaining
obstetrics and gynecology postgraduate training in Ghana, established in 1989 to
reverse low repatriation of physicians trained abroad. METHODS: All 85 certified
graduates of 2 Ghanaian university-based postgraduate training programs from
program initiation in 1989 through June 2010 were identified and eligible for
this study. Of these, 7 were unable to be contacted, inaccessible, declined
participation, or deceased. RESULTS: Of the graduates, 83 provide clinical
services in Ghana and work in 33 sites in 8 of 10 regions; 15% were the first
obstetrician and gynecologist at their facility, 25% hold clinical leadership
positions, 50% practice in teaching hospitals, and 14% serve as academic faculty.
CONCLUSIONS: Creating capacity for university-based postgraduate training in
obstetrics and gynecology is effective and sustainable for a comprehensive global
approach to reduce maternal and neonatal morbidity and mortality. Policies to
support training and research capacity in obstetrics and gynecology are an
integral part of a long-term national plan for maternal health.
PMID- 24354829
TI - Maternal stressful life events prior to conception and the impact on infant birth
weight in the United States.
AB - OBJECTIVES: We sought to determine if and to what extent a woman's exposure to
stressful life events prior to conception (PSLEs) were associated with subsequent
infant birth weight by using a nationally representative sample of US women.
METHODS: We examined 9350 mothers and infants participating in the first wave of
the Early Childhood Longitudinal Study, Birth Cohort in 2001. Weighted
regressions estimated the effect of exposure on very low and low birth weight,
adjusting for maternal sociodemographic and health factors and stress during
pregnancy. RESULTS: Twenty percent of women experienced any PSLE. In adjusted
analyses, exposed women were 38% more likely to have a very low birth weight
infant than nonexposed women. Furthermore, the accumulation of PSLEs was
associated with reduced infant birth weight. CONCLUSIONS: This was the first
nationally representative study to our knowledge to investigate the impact of
PSLEs on very low and low birth weight in the United States. Interventions aimed
to improve birth outcomes will need to shift the clinical practice paradigm
upstream to the preconception period to reduce women's exposure to stress over
the life course and improve the long-term health of children.
PMID- 24354830
TI - Preterm birth in the United States: the impact of stressful life events prior to
conception and maternal age.
AB - OBJECTIVES: We determined whether and to what extent a woman's exposure to
stressful life events prior to conception (PSLEs) was associated with preterm
birth and whether maternal age modified this relationship. METHODS: We examined
9350 mothers and infants participating in the first wave of the Early Childhood
Longitudinal Study, Birth Cohort, a nationally representative sample of US women
and children born in 2001, to investigate the impact of PSLEs on preterm birth in
the United States. We estimated the effect of exposure on preterm birth with
weighted logistic regression, adjusting for maternal sociodemographic and health
factors and stress during pregnancy. RESULTS: Of the women examined, 10.9% had a
preterm birth. In adjusted analyses, women aged 15 to 19 years who experienced
any PSLE had over a 4-fold increased risk for having a preterm birth. This
association differed on the basis of the timing of the PSLE. CONCLUSIONS:
Findings suggest that adolescence may be a sensitive period for the risk of
preterm birth among adolescents exposed to PSLEs. Clinical, programmatic, and
policy interventions should address upstream PSLEs, especially for adolescents,
to reduce the prevalence of preterm birth and improve maternal and child health.
PMID- 24354831
TI - The changing character of the Black-White infant mortality gap, 1983-2004.
AB - OBJECTIVES: We examined how changes in demographic, geographic, and childbearing
risk factors were related to changes in the Black-White infant mortality rate
(IMR) gap over 2 decades. METHODS: Using 1983-2004 Vital Statistics, we applied
inverse probability weighting methods to examine the relationship between risk
factors and 3 outcomes: the overall IMR gap, its birth weight component, and its
conditional (on birth weight) IMR component. RESULTS: The unexplained IMR gap
(the part not related to observed risk factors) was stable, changing from 5.0 to
5.3 deaths per 1000 live births. By contrast, the explained gap declined from 4.6
to 1.9. The decline in the explained gap was driven by the changing relationship
between risk factors and IMR. Further analysis revealed that most of the
unexplained gap occurred among infants weighing less than 1000 grams at birth,
whereas most of the explained gap occurred among infants weighing more than 1000
grams. CONCLUSIONS: The unexplained gap was stable over the last 2 decades, but
the explained gap declined markedly. If the stability of the unexplained gap
continues, even complete convergence of risk factors would reduce the Black-White
IMR gap by only one quarter.
PMID- 24354832
TI - Gestational weight gain and risk of infant death in the United States.
AB - OBJECTIVES: We examined the association of prepregnancy body mass index (BMI) and
gestational weight gain (GWG) with risk of death during infancy using the
Institute of Medicine's (IOM's) Pregnancy Weight Gain Guidelines. METHODS: We
obtained maternal and infant data for 2004-2008 from 159,244 women with a
singleton, full-term, live birth in the 41 states that participated in phase 5 of
the Pregnancy Risk Assessment Monitoring System. We fit logistic regression
models to estimate the association between prepregnancy BMI, GWG, and risk of
death during infancy, controlling for confounders. RESULTS: Only 34% of women
gained the IOM-recommended amount of weight during pregnancy. Infants born to
underweight, normal-weight, and overweight women with inadequate GWG had odds of
mortality during infancy that were 6.18, 1.47, and 2.11 times higher,
respectively, than those of infants born to women with adequate GWG. Infants born
to obese women with excessive weight gain had a 49% decreased likelihood of
mortality. CONCLUSIONS: A significant association exists between inadequate GWG
and infant death that weakens with increasing prepregnancy BMI; weight gain
beyond the recommended amount appears to be protective against infant mortality.
PMID- 24354833
TI - Implementation and randomized controlled trial evaluation of universal postnatal
nurse home visiting.
AB - OBJECTIVES: We evaluated whether a brief, universal, postnatal nurse home
visiting intervention can be implemented with high penetration and fidelity,
prevent emergency health care services, and promote positive parenting by infant
age 6 months. METHODS: Durham Connects is a manualized 4- to 7-session program to
assess family needs and connect parents with community resources to improve
infant health and well-being. All 4777 resident births in Durham, North Carolina,
between July 1, 2009, and December 31, 2010, were randomly assigned to
intervention and control conditions. A random, representative subset of 549
families received blinded interviews for impact evaluation. RESULTS: Of all
families, 80% initiated participation; adherence was 84%. Hospital records
indicated that Durham Connects infants had 59% fewer infant emergency medical
care episodes than did control infants. Durham Connects mothers reported fewer
infant emergency care episodes and more community connections, more positive
parenting behaviors, participation in higher quality out-of-home child care, and
lower rates of anxiety than control mothers. Blinded observers reported higher
quality home environments for Durham Connects than for control families.
CONCLUSIONS: A brief universal home-visiting program implemented with high
penetration and fidelity can lower costly emergency medical care and improve
family outcomes.
PMID- 24354834
TI - Effect of primary care intervention on breastfeeding duration and intensity.
AB - OBJECTIVES: We determined the effectiveness of primary care-based, and pre- and
postnatal interventions to increase breastfeeding. METHODS: We conducted 2 trials
at obstetrics and gynecology practices in the Bronx, New York, from 2008 to 2011.
The Provider Approaches to Improved Rates of Infant Nutrition & Growth Study
(PAIRINGS) had 2 arms: usual care versus pre- and postnatal visits with a
lactation consultant (LC) and electronically prompted guidance from prenatal care
providers (EP). The Best Infant Nutrition for Good Outcomes (BINGO) study had 4
arms: usual care, LC alone, EP alone, or LC+EP. RESULTS: In BINGO at 3 months,
high intensity was greater for the LC+EP (odds ratio [OR] = 2.72; 95% confidence
interval [CI] = 1.08, 6.84) and LC (OR = 3.22; 95% CI = 1.14, 9.09) groups versus
usual care, but not for the EP group alone. In PAIRINGS at 3 months, intervention
rates exceeded usual care (OR = 2.86; 95% CI = 1.21, 6.76); the number needed to
treat to prevent 1 dyad from nonexclusive breastfeeding at 3 months was 10.3 (95%
CI = 5.6, 50.7). CONCLUSIONS: LCs integrated into routine care alone and combined
with EP guidance from prenatal care providers increased breastfeeding intensity
at 3 months postpartum.
PMID- 24354835
TI - Association of maternal and community factors with enrollment in home visiting
among at-risk, first-time mothers.
AB - OBJECTIVES: We identified individual and contextual factors associated with
referral and enrollment in home visiting among at-risk, first-time mothers.
METHODS: We retrospectively studied referral and enrollment in a regional home
visiting program from 2007 to 2009 in Hamilton County, Ohio. Using linked vital
statistics and census tract data, we obtained individual and community measures
on first-time mothers meeting eligibility criteria for home visiting (low income,
unmarried, or age < 18 years). Generalized linear modeling was performed to
determine factors associated with relative risk (RR) of (1) referral to home
visiting among eligible mothers and (2) enrollment after referral. RESULTS: Of
8187 first-time mothers eligible for home visiting, 2775 were referred and 1543
were enrolled. Among referred women, high school completion (RR = 1.10) and any
college (RR = 1.17) compared with no high school completion were associated with
increased enrollment, and enrollment was less likely for those living in
communities with higher socioeconomic deprivation (RR = 0.71; P < .05).
CONCLUSIONS: Barriers to enrollment in home visiting persisted at multiple
ecological levels. Ongoing evaluation of enrollment in at-risk populations is
critical as home visiting programs are implemented and expanded.
PMID- 24354837
TI - Improving birth outcomes requires closing the racial gap.
PMID- 24354836
TI - Trends in maternal morbidity before and during pregnancy in California.
AB - OBJECTIVES: We examined trends in maternal comorbidities in California. METHODS:
We conducted a retrospective cohort study of 1,551,017 California births using
state-linked vital statistics and hospital discharge cohort data for 1999, 2002,
and 2005. We used International Classification of Diseases, Ninth Revision,
Clinical Modification codes to identify the following conditions, some of which
were preexisting: maternal hypertension, diabetes, asthma, thyroid disorders,
obesity, mental health conditions, substance abuse, and tobacco use. We estimated
prevalence rates with hierarchical logistic regression models, adjusting for
demographic shifts, and also examined racial/ethnic disparities. RESULTS: The
prevalence of these comorbidities increased over time for hospital admissions
associated with childbirth, suggesting that pregnant women are getting sicker.
Racial/ethnic disparities were also significant. In 2005, maternal hypertension
affected more than 10% of all births to non-Hispanic Black mothers; maternal
diabetes affected nearly 10% of births to Asian/Pacific Islander mothers (10% and
43% increases, respectively, since 1999). Chronic hypertension, diabetes,
obesity, mental health conditions, and tobacco use among Native American women
showed the largest increases. CONCLUSIONS: The prevalence of maternal
comorbidities before and during pregnancy has risen substantially in California
and demonstrates racial/ethnic disparity independent of demographic shifts.
PMID- 24354838
TI - The effects of breastfeeding exclusivity on early childhood outcomes.
AB - OBJECTIVES: We examined the relationship between breastfeeding exclusivity and
duration and children's health and cognitive outcomes at ages 2 and 4 years.
METHODS: We used the Early Childhood Longitudinal Study-Birth Cohort, a
nationally representative sample of 10,700 children born in the United States in
2001. Parent interviews and child assessments were conducted in measurement waves
at 9 months, 2 years, 4 years, and in kindergarten, with the focus on ages 2 and
4 years. We employed propensity scores as a means of adjusting for confounding
involving observed characteristics. RESULTS: Outcome analyses using propensity
scores showed some small effects of breastfeeding on key outcomes at age 4 years
but not at age 2 years. Effects appeared to be concentrated in reading and
cognitive outcomes. Overall, we found no consistent evidence for dosage effects
of breastfeeding exclusivity. Our sensitivity analyses revealed that a small
amount of unobserved confounding could be responsible for the resulting benefits.
CONCLUSIONS: Our study revealed little or no effect of breastfeeding exclusivity
and duration on key child outcomes.
PMID- 24354839
TI - Influenza vaccine text message reminders for urban, low-income pregnant women: a
randomized controlled trial.
AB - OBJECTIVES: We evaluated the impact of influenza vaccine text message reminders
in a low-income obstetric population. METHODS: We conducted a randomized
controlled trial that enrolled 1187 obstetric patients from 5 community-based
clinics in New York City. The intervention group received 5 weekly text messages
regarding influenza vaccination starting mid-September 2011 and 2 text message
appointment reminders. Both groups received standard automated telephone
appointment reminders. The prespecified endpoints were receipt of either pre- or
postpartum influenza vaccination calculated cumulatively at the end of each month
(September-December 2011). RESULTS: After adjusting for gestational age and
number of clinic visits, women who received the intervention were 30% more likely
to be vaccinated as of December 2011 (adjusted odds ratio [AOR] = 1.30; 95%
confidence interval [CI] = 1.003, 1.69 end of September: AOR = 1.34; 95% CI =
0.98, 1.85; October: AOR = 1.35; 95% CI = 1.05, 1.75; November: AOR = 1.27; 95%
CI = 0.98, 1.65). The subgroup of women early in the third trimester at
randomization showed the greatest intervention effect (December 31: 61.9%
intervention vs 49.0% control; AOR = 1.88; 95% CI = 1.12, 3.15). CONCLUSIONS: In
this low-income obstetric population, text messaging was associated with
increased influenza vaccination, especially in those who received messages early
in their third trimester.
PMID- 24354840
TI - Preterm birth and prenatal maternal occupation: the role of Hispanic ethnicity
and nativity in a population-based sample in Los Angeles, California.
AB - OBJECTIVES: We investigated preterm birth (PTB) in relation to maternal
occupational exposure and whether effect measures were modified by Hispanic
ethnicity and nativity in a population-based sample with high proportion of
Hispanics. METHODS: We used a case-control study (n = 2543) nested within a
cohort of 58,316 births in Los Angeles County, California, in 2003. We
categorized prenatal occupations using the US Census Occupation Codes and
Classification System and developed a job exposure matrix. Odds ratios for PTB
were estimated using logistic regression. RESULTS: Odds ratios for PTB were
increased for all women in health care practitioner and technical occupations,
but the 95% confidence intervals included the null value; effects were more
pronounced among Hispanics. We estimated elevated odds ratios for foreign-born
Hispanic women in building and grounds cleaning and maintenance occupations.
Shift work and physically demanding work affected births among US-born but not
foreign-born Hispanics. CONCLUSIONS: Hispanic women are at particular risk for
PTB related to adverse prenatal occupational exposure. Nativity may moderate
these effects on PTB. Maternal occupational exposures likely contribute to ethnic
disparities in PTB.
PMID- 24354841
TI - Association of access to publicly funded family planning services with adolescent
birthrates in California counties.
AB - OBJECTIVES: We examined the association of adolescent birthrates (ABRs) with
access to and receipt of publicly funded family planning services in California
counties provided through 2 state programs: Medi-Cal, California's Medicaid
program, and the Family Planning, Access, Care, and Treatment (Family PACT)
program. METHODS: Our key data sources included the California Health Interview
Survey and California Women's Health Survey, Medi-Cal and Family PACT claims
data, and the Birth Statistical Master File. We constructed a linear regression
analysis measuring the relationship of access to and receipt of family planning
services with ABRs when controlling for counties' select covariates. RESULTS: The
regression analysis indicated that a higher access rate to Family PACT in a
county was associated with a lower ABR (B = -0.19; P < .01) when controlling for
unemployment rate, percentage of foreign-born adolescents, and percentage of
adult low-income births. CONCLUSIONS: Efforts to reduce ABRs, specifically in
counties that had persistently high rates are critical to achieving a healthy
future for the state and the nation. Family PACT played a crucial role in helping
adolescents avoid unintended and early childbearing.
PMID- 24354842
TI - Layers of inequality: power, policy, and health.
PMID- 24354843
TI - The new food package and breastfeeding outcomes among women, infants, and
children participants in Los Angeles County.
AB - OBJECTIVES: We assessed the effect of the new Special Supplemental Nutrition
Program for Women, Infants, and Children (WIC) food package, implemented in
October 2009, on breastfeeding outcomes among a predominately Latina sample of
WIC participants in Los Angeles County, California. METHODS: We used data from
5020 WIC participants who were interviewed in a series of repeated cross
sectional surveys conducted in 2005, 2008, and 2011. Participants were randomly
selected from Los Angeles County residents who received WIC services during those
years. RESULTS: Consistent with the WIC population in Los Angeles, participants
were mostly Latina and had low levels of income and education; more than half
were foreign-born. We found small but significant increases from pre- to
postimplementation of the new WIC food package in prevalence of prenatal
intention to breastfeed and breastfeeding initiation, but no changes in any
breastfeeding at 3 and 6 months. The prevalence of exclusive breastfeeding at 3
and 6 months roughly doubled, an increase that remained large and significant
after adjustment for other factors. CONCLUSIONS: The new food package can improve
breastfeeding outcomes in a population at high risk for negative breastfeeding
outcomes.
PMID- 24354844
TI - Improved birth weight for Black infants: outcomes of a Healthy Start program.
AB - OBJECTIVES: We determined whether participation in Healthy Babies Healthy Start
(HBHS), a maternal health program emphasizing racial equity and delivering
services through case management home visitation, was associated with improved
birth outcomes for Black women relative to White women. METHODS: We used a
matched-comparison posttest-only design in which we selected the comparison group
using propensity score matching. Study data were generated through secondary
analysis of Michigan state- and Kalamazoo County-level birth certificate records
for 2008 to 2010. We completed statistical analyses, stratified by race, using a
repeated-measures generalized linear model. RESULTS: Despite their smoking rate
being double that of their matched counterparts, Black HBHS participants
delivered higher birth-weight infants than did Black nonparticipants (P = .05).
White HBHS participants had significantly more prenatal care than did White
nonparticipants, but they had similar birth outcomes (P = .7 for birth weight; P
= .55 for gestation). CONCLUSIONS: HBHS participation is associated with
increased birth weights among Black women but not among White women, suggesting
differential program gains for Black women.
PMID- 24354845
TI - Self-rated health mediates the association between functional status and health
related quality of life in Parkinson's disease.
AB - AIMS AND OBJECTIVES: To explore whether self-rated health acts as a potential
mediator in the association between functional status and health-related quality
of life in Parkinson's disease. BACKGROUND: Older persons (as most patients with
Parkinson's disease are) who reported poor self-rated health compared with those
with excellent self-rated health were two-and-a-half times more likely to have
experienced a decline in functional ability. DESIGN: Cross-sectional. METHODS:
Socio-demographic and clinical data of the patients (n = 176) were obtained
during a structured interview and from medical records. Functional status was
measured with the Unified Parkinson's Disease Rating Scale (total score), self
rated health with the first item of the Short-Form 36-item Health Survey
Questionnaire and health-related quality of life with the disease-specific
questionnaire called the Parkinson's Disease Quality of Life Questionnaire-39.
Multiple linear regression analyses and the Sobel test were employed to assess
mediation. RESULTS: Self-rated health seems to have a mediating effect on the
association between functional status and health-related quality of life. The
Sobel test confirmed an indirect effect of functional status via self-rated
health on health-related quality of life and showed a statistically significant
indirect effect of functional status on health-related quality of life via self
rated health against the direct route without the mediator. CONCLUSIONS: Self
rated health partially mediates the deteriorating effect of functional status on
health-related quality of life. RELEVANCE TO CLINICAL PRACTICE: Supportive and
adaptation psychosocial intervention programmes leading to restored self-rated
health may enhance the quality of life regardless of disability in Parkinson's
disease.
PMID- 24354848
TI - Effects of an idiosyncratic stimulus on functional analysis of vocal stereotypy
in two settings.
AB - OBJECTIVE: This study evaluated the effects of an idiosyncratic stimulus (Legos
plastic blocks) on vocal stereotypy by a child with pervasive developmental
disorder during functional analysis sessions conducted in analogue and natural
settings. METHODS: The presence and absence of the idiosyncratic stimulus was
controlled in a multielement experimental design that incorporated four
functional analysis conditions. RESULTS: The background presence of the
idiosyncratic stimulus was associated with a higher percentage of vocal
stereotypy in all functional analysis sessions in both settings when compared
with phases where the stimulus was absent. CONCLUSIONS: The presence or absence
of specific stimuli can alter the results of a functional analysis and produce
inaccurate conclusions about the environmental conditions that occasion problem
behavior.
PMID- 24354846
TI - The 4-cysteine zinc-finger motif of the RNA polymerase regulator DksA serves as a
thiol switch for sensing oxidative and nitrosative stress.
AB - We show that thiols in the 4-cysteine zinc-finger motif of DksA, an RNA
polymerase accessory protein known to regulate the stringent response, sense
oxidative and nitrosative stress. Hydrogen peroxide- or nitric oxide (NO)
mediated modifications of thiols in the DksA 4-cysteine zinc-finger motif release
the metal cofactor and drive reversible changes in the alpha-helicity of the
protein. Wild-type and relA spoT mutant Salmonella, but not isogenic dksA
deficient bacteria, experience the downregulation of r-protein and amino acid
transport expression after NO treatment, suggesting that DksA can regulate gene
expression in response to NO congeners independently of the ppGpp alarmone.
Oxidative stress enhances the DksA-dependent repression of rpsM, while preventing
the activation of livJ and hisG gene transcription that is supported by reduced,
zinc-bound DksA. The inhibitory effects of oxidized DksA on transcription are
reversible with dithiothreitol. Our investigations indicate that sensing of
reactive species by DksA redox active thiols fine-tunes the expression of
translational machinery and amino acid assimilation and biosynthesis in accord
with the metabolic stress imposed by oxidative and nitrosative stress. Given the
conservation of Cys(114) , and neighbouring hydrophobic and charged amino acids
in DksA orthologues, phylogenetically diverse microorganisms may use the DksA
thiol switch to regulate transcriptional responses to oxidative and nitrosative
stress.
PMID- 24354847
TI - Seasonal variation of 25-hydroxyvitamin D among non-Hispanic black and white
pregnant women from three US pregnancy cohorts.
AB - BACKGROUND: Vitamin D deficiency during pregnancy has been associated with
increased risk of complications and adverse perinatal outcomes. We evaluated
seasonal variation of 25-hydroxyvitamin D [25(OH)D] among pregnant women,
focusing on patterns and determinants of variation. METHODS: Data came from three
cohort studies in the US that included 2583 non-Hispanic Black and White women
having prenatal 25(OH)D concentrations determined. Fourier time series and
generalised linear models were used to estimate the magnitude of 25(OH)D
seasonality. We modelled seasonal variability using a stationary cosinor model to
estimate the phase shift, peak-trough difference, and annual mean of 25(OH)D.
RESULTS: We observed a peak for 25(OH)D in summer, a nadir in winter, and a phase
of 8 months, which resulted from fluctuations in 25(OH)D3 rather than 25(OH)D2.
After adjustment for covariates, the annual mean concentrations and estimated
peak-trough difference of 25(OH)D among Black women were 19.8 ng/mL [95%
confidence interval (CI) 18.9, 20.5] and 5.8 ng/mL [95% CI 4.7, 6.7], and for non
Hispanic White women were 33.0 ng/mL [95% CI 32.6, 33.4] and 7.4 ng/mL [95% CI
6.0, 8.9]. CONCLUSIONS: Non-Hispanic Black women had lower average 25(OH)D
concentrations throughout the year and smaller seasonal variation levels than non
Hispanic White women. This study's confirmation of 25(OH)D seasonality over a
calendar year has the potential to enhance public health interventions targeted
to improve maternal and perinatal outcomes.
PMID- 24354849
TI - Health policies and the relationships between socioeconomic status, access to
health care, and health.
AB - Health policies tend to focus on improving the access to health care of persons
of low-socioeconomic status to improve their health. This commentary argues that
health policies directly directed at health and socioeconomic status (and other
components of individual welfare) will also be effective if one wants to improve
the well-being of the poor.
PMID- 24354850
TI - Transcriptionally correlated subcellular dynamics of MBNL1 during lens
development and their implication for the molecular pathology of myotonic
dystrophy type 1.
AB - DM1 (myotonic dystrophy type 1) is caused by elongation of a CTG repeat in the
DMPK (dystrophia myotonica-protein kinase) gene. mRNA transcripts containing
these CUGexp (CUG expansion) repeats form accumulations, or foci, in the nucleus
of the cell. The pathogenesis of DM1 is proposed to result from inappropriate
patterns of alternative splicing caused by sequestration of the developmentally
regulated alternative splicing factor MBNL1 (muscleblind-like 1) by these foci.
Since eye lens cataract is a common feature of DM1 we have examined the
distribution and dynamics of MBNL1 in lens epithelial cell lines derived from
patients with DM1. The results of the present study demonstrate that only a small
proportion of nuclear MBNL1 accumulates in CUGexp pre-mRNA foci. MBNL1 is,
however, highly mobile and changes localization in response to altered
transcription and splicing activity. Moreover, immunolocalization studies in lens
sections suggest that a change in MBNL1 distribution is important during lens
growth and differentiation. Although these data suggest that the loss of MBNL1
function due to accumulation in foci is an unlikely explanation for DM1 symptoms
in the lens, they do demonstrate a strong relationship between the subcellular
MBNL1 localization and pathways of cellular differentiation, providing an insight
into the sensitivity of the lens to changes in MBNL1 distribution.
PMID- 24354851
TI - Optimized heterologous transfection of viable adult organotypic brain slices
using an enhanced gene gun.
AB - BACKGROUND: Organotypic brain slices (OTBS) are an excellent experimental
compromise between the facility of working with cell cultures and the biological
relevance of using animal models where anatomical, morphological, and cellular
function of specific brain regions can be maintained. The biological
characteristics of OTBS can subsequently be examined under well-defined
conditions. They do, however, have a number of limitations; most brain slices are
derived from neonatal animals, as it is difficult to properly prepare and
maintain adult OTBS. There are ample problems with tissue integrity as OTBS are
delicate and frequently become damaged during the preparative stages.
Notwithstanding these obstacles, the introduced exogenous proteins into both
neuronal cells, and cells imbedded within tissues, have been consistently
difficult to achieve. RESULTS: Following the ex vivo extraction of adult mouse
brains, mounted inside a medium-agarose matrix, we have exploited a precise
slicing procedure using a custom built vibroslicer. To transfect these slices we
used an improved biolistic transfection method using a custom made low-pressure
barrel and novel DNA-coated nanoparticles (40 nm), which are drastically smaller
than traditional microparticles. These nanoparticles also minimize tissue damage
as seen by a significant reduction in lactate dehydrogenase activity as well as
propidium iodide (PI) and dUTP labelling compared to larger traditional gold
particles used on these OTBS. Furthermore, following EYFP exogene delivery by
gene gun, the 40 nm treated OTBS displayed a significantly larger number of
viable NeuN and EYFP positive cells. These OTBS expressed the exogenous proteins
for many weeks. CONCLUSIONS: Our described methodology of producing OTBS, which
results in better reproducibility with less tissue damage, permits the
exploitation of mature fully formed adult brains for advanced neurobiological
studies. The novel 40 nm particles are ideal for the viable biolistic
transfection of OTBS by reducing tissue stress while maintaining long term
exogene expression.
PMID- 24354852
TI - A role of FCER1A and FCER2 polymorphisms in IgE regulation.
AB - BACKGROUND: Both FCER2 and FCER1A encode subunits of IgE receptors. Variants in
FCER1A were previously identified as major determinants of IgE levels in genome
wide association studies. METHODS: Here we investigated in detail whether FCER2
polymorphisms affect IgE levels alone and/or by interaction with FCER1A
polymorphisms. To cover the genetic information of FCER2, 21 single-nucleotide
polymorphisms (SNPs) were genotyped by Illumina HumanHap300 BeadChip (5 SNPs) and
the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF MS; 14 SNPs) in at least 1303 Caucasian children (651 asthmatics)
(ISAAC II/ MAGICS population); genotypes of two SNPs were imputed. RESULTS: SNP
rs3760687 showed the most consistent effect on total serum IgE levels (b [SE] =
0.38 [0.16]; P = 0.016), while FCER2 polymorphisms in general were predominantly
associated with mildly-to-moderately increased IgE levels (50th and 66th
percentiles). Gene-by-gene interaction analysis suggests that FCER2 polymorphism
rs3760687 influences IgE levels mainly in individuals not homozygous for the risk
allele of FCER1A polymorphism rs2427837, which belongs to the major IgE
determining tagging bin in the population. CONCLUSION: FCER2 polymorphism
rs3760687 affects moderately elevated total serum IgE levels, especially in the
absence of homozygosity for the risk allele of FCER1A SNP rs2427837.
PMID- 24354853
TI - A pandemic H1N1 influenza virus-like particle vaccine induces cross-protection in
mice.
AB - Influenza virus-like particles (VLPs) represent promising alternative vaccines.
However, it is necessary to demonstrate that influenza VLPs confer cross
protection against antigenically distinct viruses. In this study, a VLP vaccine
comprising hemagglutinin (HA) and M1 from the A/California/04/2009 (H1N1) were
used and its ability to induce cross-protective efficacy against heterologous
viruses A/PR/8/34 (H1N1) and A/New Caledonia/20/99 (H1N1) in mice was assessed.
Vaccination with 2009 H1 VLPs induced significantly higher levels of IgG cross
reactive with these heterologous viruses after the second boost compared to after
the prime or first boost. Lung virus titers also decreased significantly and the
lung cross-reactive IgG response after lethal virus challenge was significantly
greater in immunized mice compared to naive mice. Vaccinated mice showed 100%
protection against A/PR/8/34 and A/Caledonia/20/99 viruses with only moderate
body weight loss and induction of cross-reactive recall, IgG antibody-secreting
cell responses. The variations in HA amino acid sequences and antigenic sites
were determined and correlated with induction of cross-protective immunity. These
results indicate that VLPs can be used as an effective vaccine that confers cross
protection against antigenically distinct viruses.
PMID- 24354854
TI - A novel phenylcyclohex-1-enecarbothioamide derivative inhibits CXCL8-mediated
chemotaxis through selective regulation of CXCR2-mediated signalling.
AB - BACKGROUND AND PURPOSE: Since the CXC chemokine receptor CXCR2 and its cognate
ligand CXCL8 (IL-8) critically regulate neutrophil trafficking during
inflammation, they have been implicated in a number of inflammatory lung
diseases. Several CXCR2 antagonists have been described and the blockade of CXCR2
has shown promise in pre-clinical disease models and early clinical trials.
However, given its potential, there are fewer distinct classes of antagonists of
CXCR2 than of other clinically relevant molecular targets. Thus, we sought to
identify additional classes of compounds that alter CXCR2 function. EXPERIMENTAL
APPROACH: We used the CXCR2 Tango(TM) assay to screen an in-house library of
highly diverse chemical compounds. CX4338 [2-(benzylamino)-4,4-dimethyl-6-oxo-N
phenylcyclohex-1-enecarbothioamide] was identified from our screen and additional
studies to characterize the compound were performed. Receptor internalization and
second-messenger assays were used to assess the effects of CX4338 on CXCR2
mediated signalling. Wound healing, transwell cell migration and LPS-induced lung
inflammation in mice were used to determine the in vitro and in vivo effects of
CX4338. KEY RESULTS: CX4338 selectively inhibited CXCR2-mediated recruitment of
beta-arrestin-2 and receptor internalization, while enhancing CXCR2-mediated MAPK
activation. Additionally, CX4338 inhibited CXCL8-induced chemotaxis in CXCR2
overexpressing cells and human neutrophils. In vivo, CX4338 significantly reduced
neutrophils in bronchoalveolar lavage induced by LPS in mice. CONCLUSIONS AND
IMPLICATIONS: A novel compound CX4338 inhibited CXCR2-mediated cell migration
with a mechanism of action not previously reported. Also, selective inhibition of
CXCR2-mediated beta-arrestin-2 activation is sufficient to inhibit CXCL8-mediated
chemotaxis.
PMID- 24354856
TI - The sandwich model: the 'music and dance' of therapeutic action.
AB - My premise is that a 'layered' approach is necessary to understand the process of
exchanges that result in therapeutic change. I imagine these processes occurring
in three layers - although the number of domains in which change is taking place
is actually infinite - such as in a sandwich. The top layer, or top slice of
bread of the sandwich, represents a broad view of the change process; it is non
linear and includes the feature of uncertainty, a general principle of dynamic
systems theory. The middle layer, or the meat of the sandwich, is explained by
theories that are immediately and clinically useful to a therapist, such as
psychoanalytic theories. These are primarily linear theories and use language and
symbols to 'tell a story of what happened'. The bottom layer, or bottom slice of
bread of the sandwich, is the micro-process; this layer includes the moment-to
moment patterns of coordinated rhythms that both communicate meaning and provide
the essential scaffold for all higher-level change processes. The micro-process
also requires a non-linear theory to make sense of its variability and emergent
properties. Taking a bite out of the sandwich will include a 'polysemic bundle of
communicative behaviors' (Harrison and Tronick, 2011). I will illustrate the
'sandwich model' with the clinical case of the analytic treatment of a 5 year-old
boy.
PMID- 24354855
TI - The early history of ideas on brief interventions for alcohol.
AB - AIMS: This study explores the early development of brief interventions for
alcohol using a history of ideas approach with a particular focus on intervention
content. METHODS: The source publications of the key primary studies published
from approximately 1962 to 1992 were examined, followed by a brief review of the
earliest reviews in this field. These studies were placed in the context of
developments in alcohol research and in public health. RESULTS: After early
pioneering work on brief interventions, further advances were not made until
thinking about alcohol problems and their treatment, most notably on controlled
drinking, along with wider changes in public health, created new conditions for
progress. There was then a golden era of rapid advance in the late 1980s and
early 1990s, when preventing the development of problem drinking became important
for public health reasons, in addition to helping already problematic drinkers.
Many research challenges identified at that time remain to be met. The content of
brief interventions changed over the period of study, although not in ways well
informed by research advances, and there were also obvious continuities, with a
renewed emphasis on the facilitation of self-change being one important
consequence of the development of internet applications. CONCLUSIONS: Ideas about
brief interventions have changed in important ways. Brief interventions have been
studied with different populations of drinkers, with aims embracing both
individual and population-level perspectives, and without well-specified
contents. The brief intervention field is an appropriate target for further
historical investigations, which may help thinking about addressing alcohol and
other problems.
PMID- 24354858
TI - Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of
individual difference in consideration of future consequences.
AB - This research examines the influence of individual difference in consideration of
future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e.,
perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and
safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1
vaccine). A survey of 411 college students showed that consideration of future
consequences had no direct effect on vaccine uptake, but higher consideration of
future consequences was associated with greater perceived severity of the flu,
higher perceived effectiveness of the vaccine, and greater perceived self
efficacy. Additional analysis suggested that consideration of future consequences
had a significant indirect effect on vaccine uptake through perceived vaccine
efficacy. Results of the study also revealed gender and racial differences in
some of the H1N1-related health beliefs. Implications of the findings for vaccine
risk communication are discussed.
PMID- 24354857
TI - The impact of the use of antiepileptic drugs on the growth of children.
AB - BACKGROUND: This study investigated whether long-term treatment with
antiepileptic drugs (AEDs) had negative effects on statural growth and serum
calcium levels in children with epilepsy in Taiwan. METHODS: Children with
epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year
were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11
boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15
boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys
and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys
and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were
selected as the controls. RESULTS: One year of VPA treatment significantly
impaired the statural growth of pediatric patients with epilepsy (p < 0.005)
compared with the control group. The underlying mechanism may have been due to
the direct effect of VPA on the proliferation of growth plate chondrocytes rather
than alterations of serum calcium. CONCLUSIONS: These results raise serious
concerns about the growth of pediatric epilepsy patients who use AEDs, and
potentially the need to closely monitor growth in children with epilepsy and
adolescents under AED treatment, especially VPA.
PMID- 24354859
TI - Health status and utilisation of the healthcare system by homeless and non
homeless people in Vienna.
AB - This case-control study describes the health situation, internal and external
resources, and utilisation of healthcare facilities by a marginalised population
consisting of homeless people in Vienna, Austria, compared with a non-homeless
control population. Among the homeless group, participants lived in halfway
houses (70%) or permanent housing (30%) in Vienna. Personal interviews were
conducted in July 2010 with 66 homeless individuals, and their data were compared
with data from non-homeless subjects from the Austrian Health Interview Survey
using conditional logistic regression. Compared with the control group, homeless
persons suffered more often from chronic diseases (P < 0.001) and rated their
health considerably lower than the comparison group (P < 0.001). Homeless people
suffered significantly more often from psychiatric disorders, respiratory
diseases, hypertension (P < 0.001), digestive system diseases (P = 0.002) and
heart diseases (P = 0.015) in comparison with the control group. Additionally,
among homeless and non-homeless individuals, the former more often consulted a
general practitioner in a period of 28 days (P = 0.002). A significantly greater
proportion of homeless people did not have any teeth (P = 0.024) and smoked
significantly more (P = 0.002). The results demonstrate deficits in the areas of
health, health behaviour, and individual and social resources of homeless people,
even though homeless people seek medical care at a higher rate than controls.
Continuing health promotion projects for this high-risk group and the
strengthening of social resources are recommended.
PMID- 24354860
TI - Common glycoproteins expressing polylactosamine-type glycans on matched patient
primary and metastatic melanoma cells show different glycan profiles.
AB - Recently, we reported comparative analysis of glycoproteins which express cancer
specific N-glycans on various cancer cells and identified 24 glycoproteins having
polylactosamine (polyLacNAc)-type N-glycans that are abundantly present in
malignant cells [ Mitsui et al., J. Pharm. Biomed. Anal. 2012 , 70 , 718 - 726 ].
In the present study, we applied the technique to comparative studies on common
glycoproteins present in the matched patient primary and metastatic melanoma cell
lines. Metastatic melanoma cells (WM266-4) contained a large amount of polyLacNAc
type N-glycans in comparison with primary melanoma cells (WM115). To identify the
glycoproteins expressing these N-glycans, glycopeptides having polyLacNAc-type N
glycans were captured by a Datura stramonium agglutinin (DSA)-immobilized agarose
column. The captured glycopeptides were analyzed by LC/MS after removing N
glycans, and some glycoproteins such as basigin, lysosome-associated membrane
protein-1 (LAMP-1), and chondroitin sulfate proteoglycan 4 (CSPG4) were
identified in both WM115 and WM266-4 cells. The expression level of polyLacNAc of
CSPG4 in WM266-4 cells was significantly higher than that in WM115 cells. In
addition, sulfation patterns of chondroitin sulfate (CS) chains in CSPG4 showed
dramatic changes between these cell lines. These data show that characteristic
glycans attached to common proteins observed in different stages of cancer cells
will be useful markers for determining degree of malignancies of tumor cells.
PMID- 24354862
TI - Mandibular asymmetry: a three-dimensional quantification of bilateral condyles.
AB - INTRODUCTION: The shape and volume of the condyle is considered to play an
important role in the pathogenesis of the mandibular deviation. Curvature
analysis is informative for objectively assess whether the shape of the condyles
matches that of the glenoid fossa. In this study, a three-dimensional (3-D)
quantification of bilateral asymmetrical condyles was firstly conducted to
identify the specific role of 3-D condylar configuration for mandibular
asymmetry. METHODS: 55 adult patients, 26 males (26 +/- 5 yrs) and 29 females (26
+/- 5 yrs), diagnosed with mandibular asymmetry were included. The examination of
deviation of chin point, deviation of dental midlines, inclination of occlusal
plane, and depth of the mandibular occlusal plane were conducted. After the
clinical investigation, computed tomography images from the patients were used to
reconstruct the 3-D mandibular models. Then the condylar volume, surface size,
surface curvature and bone mineral density were evaluated independently for each
patient on non-deviated and deviated sides of temporomandibular joint. RESULTS:
Both the condylar surface size and volume were significantly larger on deviated
side (surface size: 1666.14 +/- 318.3 mm2, volume: 1981.5 +/- 418.3 mm3). The
anterior slope of the condyle was flatter (0.12 +/- 0.06) and the posterior slope
(0.39 +/- 0.08) was prominently convex on the deviated side. The corresponding
bone mineral density values were 523.01 +/-118.1 HU and 549.07 +/-120. 6 HU on
anterior and posterior slopes. CONCLUSIONS: The incongruence presented on the
deviated side resulted in a reduction in contact areas and, thus, an increase in
contact stresses and changes of bone density. All aforementioned results suggest
that the difference existing between deviated and non-deviated condyles
correlates with facial asymmetrical development. In mandibular asymmetry
patients, the 3-D morphology of condyle on deviated side differ from the non
deviated side, which indicates the association between asymmetrical jaw function
and joint remodeling.
PMID- 24354861
TI - Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress.
AB - Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them
from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function,
enhancing immune responses to bound peptides. We questioned whether HSP70i
differentially protects control and vitiligo melanocytes from stress and
subsequent immune responses. We compared expression of HSP70i in skin samples,
evaluated the viability of primary vitiligo and control melanocytes exposed to
bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i
traffics to melanosomes to contact immunogenic proteins by cell fractionation,
western blotting, electron microscopy, and confocal microscopy. Viability of
vitiligo and control melanocytes was equally affected under stress. However,
vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH,
corroborating with aberrant HSP70i expression in patient skin. Intracellular
HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo
melanocytes. Thus, whereas either agent is cytotoxic to melanocytes, MBEH
preferentially induces immune responses to melanocytes.
PMID- 24354863
TI - Evaluation of two commercial omalizumab/free IgE immunoassays: implications of
use during therapy.
AB - BACKGROUND: The anti-IgE monoclonal antibody, omalizumab, is approved in the US
as add-on therapy for patients >=12 years of age with moderate-to-severe
persistent allergic asthma. Omalizumab is administered according to the US Food
and Drug Administration approved dosing table included in the prescribing
information. The dosing table was developed using Genentech's free IgE assay and
is designed to achieve free serum IgE levels of <50 ng/mL, known to be associated
with clinical benefit. Lack of clinical benefit in a subset of patients on
omalizumab has prompted demand for commercial free IgE assays to guide omalizumab
dosing. To date, two commercial free IgE assays marketed by ViraCor-IBT (no
longer offered) and BioTeZ have been available to physicians. OBJECTIVE: This
study compares the results generated from the two commercial free IgE assays with
the free IgE levels generated by the Genentech assay. METHODS: Two serum sample
sets were prepared using 20 samples from patients with a wide range of IgE and
omalizumab from an omalizumab clinical trial and 36 samples from omalizumab-naive
patients. Different amounts of omalizumab were added to the 36 omalizumab naive
samples based on measured total IgE levels to ensure that a good range of IgE and
omalizumab was represented in the study samples. Samples were randomized for
blinded analysis of free IgE levels using the Genentech, ViraCor-IBT and BioTeZ
free serum IgE assays. Analysis of samples in the ViraCor-IBT assay were
conducted by ViraCor-IBT and the analysis of samples using the Genentech and
BioTeZ assay methods were conducted by a third party contract research
organization. RESULTS: The ViraCor-IBT and BioTeZ free IgE assays demonstrated
significantly higher free IgE levels than the Genentech free IgE assay. Twenty
nine of 56 samples tested <50 ng/mL in the Genentech assay; of these, 12/29 (41%)
and 20/29 (69%) tested >50 ng/mL in the BioTeZ and ViraCor-IBT assays,
respectively. In the BioTeZ free IgE evaluations, 11/20 samples that were re
tested had inter-assay differences ranging from 40-190%. CONCLUSIONS: Free ligand
(such as IgE) measurements are challenging and dependent on the method and
reagents used. The Viracor-IBT and BioTeZ methods tend to over-estimate free
serum IgE levels compared with the Genentech free IgE assay. Using these assays
to monitor therapy and adjust omalizumab doses post treatment is considered off
label use and could lead to a potential risk for unnecessary treatment and/or
risk to patient safety.
PMID- 24354864
TI - Podoplanin expression in cancer-associated fibroblasts enhances tumor progression
of invasive ductal carcinoma of the pancreas.
AB - BACKGROUND: Interactions between cancer cells and surrounding cancer-associated
fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal
carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective
tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2
40), and expression of PDPN by stromal CAFs has been reported to be a prognostic
indicator in various types of cancer. METHODS: Expression of PDPN in pancreatic
IDCs was assessed by immunohistochemical examination in 105 patients who
underwent pancreatic resection. Primary CAFs were established from pancreatic
cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase
chain reaction and flow cytometric analysis were performed to investigate PDPN
expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the
functional differences between PDPN+ CAFs and PDPN- CAFs using indirect co
culture with pancreatic cancer cell lines. We also investigated the culture
conditions to regulate PDPN expression in CAFs. RESULTS: PDPN expression in
stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461),
vascular invasion (P = 0.0101), tumor size >= 3 cm (P = 0.0038), histological
grade (P = 0.0344), Union for International Cancer Control classification T stage
(P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed
heterogeneous PDPN expression in vitro. Moreover, migration and invasion of
pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN
expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase
(MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under
several conditions including co-culture with cancer cells, different culture
media, and addition of growth factor. CONCLUSIONS: PDPN-expressing CAFs enhance
the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an
independent predictor of poor outcome. Understanding the regulation of the tumor
microenvironment is an important step towards developing new therapeutic
strategies.
PMID- 24354865
TI - Phenylephrine eye drops in pediatric patients undergoing ophthalmic surgery:
incidence, presentation, and management of complications during general
anesthesia.
AB - BACKGROUND: Phenylephrine eye drops are widely used as mydriatic agent to reach
the posterior segment of the eye. In literature, many reports suggest a systemic
absorption of this agent as a source of severe adverse drug reactions. Hence, we
reviewed our experience with topical phenylephrine in ophthalmic surgery.
METHODS: In May 2006, following US guidelines publication, a standard operating
procedure was issued in our operating rooms to standardize the use of
phenylephrine eye drops in our practice. Two years later, after the occurrence of
a cluster of serious adverse drug reactions in infants undergoing surgery, a
review of phenylephrine safety and systemic complications incidence was
performed. RESULTS: We observed 451 pediatric patients, and 187 met the
inclusions criteria: Among them, 4 experienced hemodynamic complications due to
phenylephrine eye drops. The incidence of major complications was 2.1%.
CONCLUSIONS: Two different patterns of side effects occurred. The first one was a
cardiovascular derangement with severe hypertension and heart rate alterations;
the other one involved exclusively pulmonary circuit causing early edema. These
clinical manifestations, their duration, and treatment responses are all
explainable by alfa1-adrenergic action of phenylephrine. This hypothetic
pathogenesis has been confirmed also by the usefulness of direct vasodilators
(anesthetic agents) and by the negative outcome occurred in the past with the use
of beta-blockers.
PMID- 24354866
TI - Prevalence of diabetes and hypertension and association with various risk factors
among different Muslim populations of Manipur, India.
AB - BACKGROUND: Type 2 Diabetes mellitus (DM) and hypertension (HT) are among the
most common non-communicable chronic diseases in developed and developing
countries around the world. The study reports the prevalence of DM and HT and its
influence from its possible risk factors. METHODS: Individuals of both sexes
(Male-1099, Female-669) belonging to six different populations were randomly
selected and screened for diabetes and hypertension following from different
districts of Manipur, which is a small hilly state, situated in the north eastern
extreme corner of India sharing an international boundary with Myanmar (Burma).
"Diabetes mellitus" and "hypertension" were defined by the American Diabetes
Association and the Joint National Committee's 7th Report guidelines,
respectively. RESULTS: The overall prevalence of diabetes and hypertension in the
entire study population was found to be 16.63% and 18.16% respectively. About
13.8% individuals had shown co-prevalence of Diabetes Mellitus and Hypertension.
The association of Diabetes Mellitus with different risk factors such as
consumption of alcohol and difference in physical activities were found to be
statistically significant. The association of Diabetes Mellitus with different
populations and age groups are also statistically significant. The association
between Hypertension with different populations and different physical activities
were also found to be statistically significant.
PMID- 24354867
TI - The AJT report.
PMID- 24354869
TI - Revisiting multi-organ transplantation in the setting of scarcity.
AB - In the setting of organ scarcity, the ethics of multi-organ transplantation (MOT)
deserve new examination. MOT offers substantial benefits to certain recipients,
including avoiding serial surgeries. However, MOT candidates in the United States
commonly receive priority for their nonprimary organ over many individuals who
need that organ, which may undermine equity. The absence of standard criteria for
MOT eligibility also enables large and unfair regional variation in MOT, such as
simultaneous liver-kidney transplantation. Unfortunately, MOT may also undermine
utility (optimal patient and graft survival) in circumstances where providing
multiple organs to one person fails to achieve the greater collective benefit
attained by providing transplants to multiple people. Policy reforms should
include the adoption of minimal clinical criteria for MOT candidacy with the
attendant goal of decreasing regional variation in MOT. In the future, these
minimal criteria can be revised to accommodate new research about which patients
derive the most benefit from MOT. Incentives to perform MOT should also be
reduced, such as by including MOT outcomes in center-specific reports. These
reforms run the risk that the transplant community could be perceived as
abandoning MOT candidates, but offer an opportunity to align transplant practice
and ethical principles.
PMID- 24354870
TI - Attenuation of donor-reactive T cells allows effective control of allograft
rejection using regulatory T cell therapy.
AB - Regulatory T cells (Tregs) are essential for the establishment and maintenance of
immune tolerance, suggesting a potential therapeutic role for Tregs in
transplantation. However, Treg administration alone is insufficient in inducing
long-term allograft survival in normal hosts, likely due to the high frequency of
alloreactive T cells. We hypothesized that a targeted reduction of alloreactive T
effector cells would allow a therapeutic window for Treg efficacy. Here we show
that preconditioning recipient mice with donor-specific transfusion followed by
cyclophosphamide treatment deleted 70-80% donor-reactive T cells, but failed to
prolong islet allograft survival. However, infusion of either 5 * 10(6) Tregs
with direct donor reactivity or 25 * 10(6) polyclonal Tregs led to indefinite
survival of BALB/c islets in more than 70% of preconditioned C57BL/6 recipients.
Notably, protection of C3H islets in autoimmune nonobese diabetic mice required
islet autoantigen-specific Tregs together with polyclonal Tregs. Treg therapy led
to significant reduction of CD8(+) T cells and concomitant increase in endogenous
Tregs among graft-infiltrating cells early after transplantation. Together, these
results demonstrate that reduction of the donor-reactive T cells will be an
important component of Treg-based therapies in transplantation.
PMID- 24354872
TI - Prognostic implications of preoperative aerobic capacity and exercise oscillatory
ventilation after liver transplantation.
AB - Our aim was to determine preoperative aerobic capacity (oxygen uptake [V'O2 ])
and prevalence of exercise oscillatory ventilation (EOV), underlying clinical
characteristics of patients with EOV, and significance of reduced aerobic
capacity and EOV in predicting mortality after liver transplantation. We
prospectively studied 263 patients who underwent elective liver transplantation.
Patients were followed up for 1 year. Despite minor impairment of resting
cardiopulmonary function, preoperative aerobic capacity was reduced (peak V'O2 :
64 +/- 19% predicted). EOV occurred in 10% of patients. Model for End-Stage Liver
Disease score tended to be higher in patients with EOV compared to patients
without, but failed to reach significance (p = 0.09). EOV patients had lower peak
V'O2 and higher ventilatory drive. EOV was more frequent in nonsurvivors than in
survivors (30% vs. 9%, p = 0.01) and was independently associated with
posttransplant all-cause 1-year mortality. Reduced peak V'O2 best predicted the
primary composite endpoint defined as 1-year mortality and/or prolonged
hospitalization and early in-hospital mortality. Multivariate analysis revealed
EOV (chi(2), 3.96; p = 0.04) and V'O2 (chi(2), 4.28; p = 0.04) as independent
predictors of mortality and so-called primary composite endpoint, respectively.
EOV and reduced peak V'O2 may identify high-risk candidates for liver
transplantation, which would motivate a more aggressive treatment when detected.
PMID- 24354871
TI - Costimulation blockade alters germinal center responses and prevents antibody
mediated rejection.
AB - De novo donor-specific antibody (DSA) after organ transplantation promotes
antibody-mediated rejection (AMR) and causes late graft loss. Previously, we
demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus
and alefacept (AMR regimen) reliably induced early DSA production with AMR in a
nonhuman primate kidney transplant model. Five animals were assigned as positive
AMR controls, four received additional belatacept and four received additional
anti-CD40 mAb (2C10R4). Notably, production of early de novo DSA was completely
attenuated with additional belatacept or 2C10R4 treatment. In accordance with
this, while positive controls experienced a decrease in peripheral IgM(+) B
cells, bela- and 2C10R4-added groups maintained a predominant population of
IgM(+) B cells, potentially indicating decreased isotype switching. Central
memory T cells (CD4(+) CD28(+) CD95(+)) as well as PD-1(hi) CD4(+) T cells were
decreased in both bela-added and 2C10R4-added groups. In analyzing germinal
center (GC) reactions in situ, lymph nodes further revealed a reduction of B cell
clonal expansion, GC-follicular helper T (Tfh) cells, and IL-21 production inside
GCs with additional belatacept or 2C10R4 treatment. Here we provide evidence that
belatacept and 2C10R4 selectively suppresses the humoral response via regulating
Tfh cells and prevents AMR in this nonhuman primate model.
PMID- 24354873
TI - Postanastomotic transplant renal artery stenosis: association with de novo class
II donor-specific antibodies.
AB - In this study, we analyze the outcomes of transplant renal artery stenosis
(TRAS), determine the different anatomical positions of TRAS, and establish
cardiovascular and immunological risk factors associated with its development.
One hundred thirty-seven of 999 (13.7%) patients had TRAS diagnosed by
angiography; 119/137 (86.9%) were treated with angioplasty, of which 113/137
(82.5%) were stented. Allograft survival in the TRAS+ intervention, TRAS+
nonintervention and TRAS- groups was 80.4%, 71.3% and 83.1%, respectively. There
was no difference in allograft survival between the TRAS+ intervention and TRAS-
groups, p = 0.12; there was a difference in allograft survival between the TRAS-
and TRAS+ nonintervention groups, p < 0.001, and between the TRAS+ intervention
and TRAS+ nonintervention groups, p = 0.037. TRAS developed at the anastomosis,
within a bend/kink or distally. Anastomotic TRAS developed in living donor
recipients; postanastomotic TRAS (TRAS-P) developed in diabetic and older
patients who received grafts from deceased, older donors. Compared with the TRAS-
group, patients with TRAS-P were more likely to have had rejection with
arteritis, odds ratio (OR): 4.83 (1.47-15.87), p = 0.0095, and capillaritis, OR:
3.03 (1.10-8.36), p = 0.033. Patients with TRAS-P were more likely to have
developed de novo class II DSA compared with TRAS- patients hazard ratio: 4.41
(2.0-9.73), p < 0.001. TRAS is a heterogeneous condition with TRAS-P having both
alloimmune and traditional cardiovascular risk factors.
PMID- 24354874
TI - Unique B cell differentiation profile in tolerant kidney transplant patients.
AB - Operationally tolerant patients (TOL) display a higher number of blood B cells
and transcriptional B cell signature. As they rarely develop an allo-immune
response, they could display an abnormal B cell differentiation. We used an in
vitro culture system to explore T-dependent differentiation of B cells into
plasma cells. B cell phenotype, apoptosis, proliferation, cytokine,
immunoglobulin production and markers of differentiation were followed in blood
of these patients. Tolerant recipients show a higher frequency of CD20(+)
CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naive B cells
compared to patients with stable graft function, correlating with a decreased
frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of
abnormal B cell differentiation. B cells from TOL proliferate normally but
produce more IL-10. In addition, B cells from tolerant recipients exhibit a
defective expression of factors of the end step of differentiation into plasma
cells and show a higher propensity for cell death apoptosis compared to patients
with stable graft function. This in vitro profile is consistent with down
regulation of B cell differentiation genes and anti-apoptotic B cell genes in
these patients in vivo. These data suggest that a balance between B cells
producing IL-10 and a deficiency in plasma cells may encourage an environment
favorable to the tolerance maintenance.
PMID- 24354875
TI - Intraplaque hemorrhage in cardiac allograft vasculopathy.
AB - Plaque hemorrhage, inflammation and microvessel density are key determinants of
plaque vulnerability in native coronary atherosclerosis (ATS). This study
investigates the role of intraplaque hemorrhage (IPH) and its relation with
inflammation and microvessels in cardiac allograft vasculopathy (CAV) in
posttransplanted patients. Seventy coronary plaques were obtained from 12
patients who died because of CAV. For each patient we collected both native heart
and the allograft, at the time of transplantation and autopsy, respectively.
Intralesion inflammation, microvessels and IPH were assessed semi-quantitatively.
IPH was observed in 21/35 (60%) CAV lesions and in 8/35 (22.9%) native ATS
plaques, with a strong association between fibrocellular lesions and IPH (p =
0.0142). Microvessels were detected in 26/35 (74.3%) of CAV lesions with
perivascular leakage as sign of endothelial damage in 18/26 (69.2%). IPH was
strongly associated with microvessels (p < 0.0001). Inflammation was present in
31/35 (88.6%) of CAV lesions. CAV IPH+ lesions were characterized by presence of
both fresh and old hemorrhage in 12/21 (57.1%). IPH, associated with microvessel
damage and inflammation, is an important feature of CAV. Fresh and old
intralesion hemorrhage suggests ongoing remodeling processes promoting the lesion
progression and vulnerability.
PMID- 24354876
TI - Donor hemosiderosis does not affect liver function and regeneration in the
setting of living donor liver transplantation.
AB - Living donor liver transplantation (LDLT) demands a careful assessment of
abnormal findings discovered during the evaluation process to determine if there
will be any potential risks to the donor or recipient. Varying degrees of
elevated hepatic iron levels are not uncommonly seen in otherwise healthy
individuals. We questioned whether mild expression of hemosiderin deposition
presents a safety concern when considering outcomes of living donation for both
the donor and the recipient. We report on three LDLT patients who were found to
have low- to moderate-grade hemosiderin deposition on liver biopsy. All other
aspects of their evaluation proved satisfactory, and the decision was made to
proceed with donation. There were no significant complications in the donors, and
all demonstrated complete normalization of liver function postoperatively, with
appropriate parenchymal regeneration. The recipients also had unremarkable
postoperative recovery. We conclude that these individuals can be considered as
potential donors after careful evaluation.
PMID- 24354877
TI - The application of indocyanine green to evaluate duodenal perfusion in pancreas
transplantation.
AB - In cases of suspected duodenal ischemia during pancreas transplantation, surgical
decisions severely affect the outcome of the patient and the graft. The use of a
nontoxic intravenous tracer, indocyanine green, allows the surgeon to evaluate
the perfusion of tissues within seconds of injection. Its application to pancreas
transplantation has not been reported previously.
PMID- 24354880
TI - Effects of a functional variant c.353T>C in snai1 on risk of two contextual
diseases. Chronic obstructive pulmonary disease and lung cancer.
AB - RATIONALE: Epithelial-mesenchymal transition (EMT) plays a key role in the
development of chronic obstructive pulmonary disease (COPD) and lung cancer.
OBJECTIVES: There are five major EMT regulatory genes (Snai1, Slug, Zeb1, Zeb2,
and Twist1) involved in EMT. We hypothesized that germline variants in these
genes may influence the development of both diseases. METHODS: Seven genetic
variants were genotyped in two two-stage case-control studies with 2,072 lung
cancer cases and 2,077 control subjects, and 1,791 patients with COPD and 1,940
control subjects to show their associations with development of both diseases.
MEASUREMENTS AND MAIN RESULTS: An exon variant c.353T>C(p.Val118Ala) of Snai1
harbored decreased risks of lung cancer (CT/CC vs. TT: odds ratio [OR], 0.76; 95%
confidence interval [CI], 0.65-0.90) and COPD (CC vs. CT vs. TT: OR, 0.75; 95%
CI, 0.63-0.89), and c.353T>C affected lung cancer risk indirectly through COPD
(COPD accounted for 6.78% of effect that the variant had on lung cancer).
Moreover, c.353T>C was correlated with lung cancer stages in smoking patients (P
= 0.013), and those with the c.353C genotypes were less likely to have metastasis
at diagnosis than those with the c.353TT genotype (OR, 0.60; 95% CI, 0.41-0.88).
The c.353C allele encoding p.118Ala attenuated Snai1's ability to up-regulate
mesenchymal biomarkers (i.e., fibronectin and vimentin) expression, and to
promote EMT-like changes, including morphologic changes, cell migration, and
invasion. However, these effects were not observed for the other variants.
CONCLUSIONS: The functional germline variant c.353T>C (p.Val118Ala) of Snai1
confers consistently decreased risks of lung cancer and COPD, and this variant
affects lung cancer risk through a mediation effect of COPD.
PMID- 24354881
TI - Absolute configuration study of a new dimeric indole alkaloid from the leaves and
twigs of Psychotria henryi.
AB - From the leaves and twigs of Psychotria henryi, a new dimeric indole alkaloid,
named psychohenin, was isolated, whose structure was elucidated on the basis of
extensive spectroscopic analysis. The absolute configuration of psychohenin was
determined by a single-crystal X-ray diffraction study using a mirror Cu Kalpha
radiation.
PMID- 24354883
TI - Risk factors for high and low placental weight.
AB - BACKGROUND: Placental weight is an independent predictor of adverse perinatal
outcome. However, risk factors for high and low placental weight are poorly
understood. The objective of this study was to identify maternal, placental, and
umbilical cord determinants of placental weight, before and after accounting for
birthweight. METHODS: This cohort study of 87,600 singleton births at the Royal
Victoria Hospital in Montreal, Canada assessed the relationship between maternal,
placental, and umbilical cord characteristics and placental weight (standardised
for sex and gestational age). We separately examined risk factors for high (z
score >+1) and low (z-score <-1) placental weight. Multivariable logistic
regression was used to study associations after adjusting for confounders and
further adjusting for birthweight. RESULTS: Chronic hypertension was associated
with low placental weight {relative risk (RR) 2.1 [95% confidence interval (CI)
1.8, 2.4] and 1.8 [95% CI 1.5, 2.1] before and after accounting for birthweight},
while pre-eclampsia was associated with low placenta weight before, but not after
adjustment for birthweight. Anaemia and gestational diabetes were linked with
high placental weight (RRs 1.2-1.4, respectively) before and after adjustment for
birthweight, while smoking was linked with high placental weight only after
adjustment for birthweight (RR 1.4 [95% CI 1.3, 1.5]). Placental and cord
determinants of high placental weight included chorioamnionitis,
chorangioma/chorangiosis, circumvallate placenta, marginal cord insertion, and
other cord abnormalities. CONCLUSIONS: The broad range of risk factors for high
placental weight suggests multiple aetiologic pathways. Future work should seek
to understand the pathways by which the placenta adapts to unfavourable
intrauterine conditions, which may provide insights into potential therapies.
PMID- 24354882
TI - Chronic urticaria in Chinese population: a hospital-based multicenter
epidemiological study.
AB - BACKGROUND: The epidemiologic profiles of chronic urticaria (CU) vary
considerably among regions, and few such data are available from China. METHODS:
We performed a multicenter open questionnaire investigation about the clinical
and laboratory features of CU, defined as recurrent wheals with/without
angioedema lasting for >=6 weeks, among 3027 patients. RESULTS: Female
preponderance was observed (female/male ratio, 1.46 : 1). The mean age at
diagnosis was 34.7 +/- 13.8 years, and the mean disease duration was 18.5 +/-
46.1 months (range, 1.5-127 months). Patients were classified as having chronic
spontaneous urticaria (CSU, 61.0% of patients), physical urticaria (PU, 26.2%),
or other urticaria types (OU, 2.3%). Nocturnal attacks were reported by 60% of
cases. The Urticaria Activity Score (UAS) in patients with CSU was 3.8 +/- 1.4.
The mean Dermatology Life Quality Index was 7.3 +/- 3.4 (range 0-30). Induction
or exacerbation of wheals with alcohol drinking was reported by 55.7% of
patients. Chronic hepatitis B was less prevalent in our CU patients compared with
the general Chinese population (2.7% vs 7%). Positive autologous serum skin tests
(ASSTs) were observed in 66.9% of patients. Patients with positive ASST had
higher UAS, greater angioedema frequencies, longer disease durations, and poorer
QoL compared with patients with negative ASST (P < 0.05). CONCLUSION: In this
Chinese population, CU usually affected youth, and CSU was the most common
subtype. Autoreactivity and alcohol consumption were the top two triggers for CU,
whereas latent infectious and chronic inflammatory diseases were not as common as
in previous reports.
PMID- 24354884
TI - Community-based interventions to promote management for older people: an
integrative review.
AB - AIMS AND OBJECTIVES: To review community programmes promoting self-care or self
management for older people with chronic disease in Thailand. BACKGROUND:
Identifying successful elements of culturally appropriate and effective community
based interventions to promote self-care with chronic illness is increasingly
important. DESIGN: Integrative review. DATA SOURCES: CINAHL, Medline, Health
Source Nursing Academic databases. METHODS: Integrative review of peer-reviewed
articles written between 1946-2012. Articles were included if they described self
care, self-management, chronic disease and community care interventions targeting
older people in Thailand. RESULTS: Of the 58 articles retrieved, only 13 articles
met the eligibility criteria. Elements of effective interventions included: (1)
providing culturally sensitive information, (2) including approaches of shared
decision-making and mutual goal setting and (3) flexibility within the
intervention to adapt to participant needs. CONCLUSIONS: Shared decision-making
and mutual goal setting between interventionists and patients improved health
behaviours and outcomes. Moreover, the flexibility to adopt the intervention to
local characteristics demonstrated positive results. RELEVANCE TO CLINICAL
PRACTICE: Promoting effective self-care and self-management behaviours is
critical to improving outcomes for chronic conditions. The tailoring and
targeting of interventions appropriate to individuals and communities are likely
to be most effective in leveraging behaviour change. This review has identified
that mutual goal setting improved health behaviours. The flexibility to adopt
self-care interventions to community-based settings showed improved patient
outcomes.
PMID- 24354885
TI - Young children's interpretation of multidigit number names: from emerging
competence to mastery.
AB - This study assessed whether a sample of two hundred seven 3- to 7-year-olds could
interpret multidigit numerals using simple identification and comparison tasks.
Contrary to the view that young children do not understand place value, even 3
year-olds demonstrated some competence on these tasks. Ceiling was reached by
first grade. When training was provided, there were significant gains, suggesting
that children can improve their partial understandings with input. Findings add
to what is known about the processes of symbolic development and the incidental
learning that occurs prior to schooling, as well as specifying more precisely
what place value misconceptions remain as children enter the educational system.
PMID- 24354886
TI - The relationship between emergency department crowding and patient outcomes: a
systematic review.
AB - PURPOSE: Emergency department (ED) crowding is a significant patient safety
concern associated with poor quality of care. The purpose of this systematic
review is to assess the relationship between ED crowding and patient outcomes.
DESIGN: We searched the Medline search engine and relevant emergency medicine and
nursing journals for studies published in the past decade that pertained to ED
crowding and the following patient outcome measures: mortality, morbidity,
patient satisfaction, and leaving the ED without being seen. All articles were
appraised for study quality. FINDINGS: A total of 196 abstracts were screened and
11 articles met inclusion criteria. Three of the eleven studies reported a
significant positive relationship between ED crowding and mortality either among
patients admitted to the hospital or discharged home. Five studies reported that
ED crowding is associated with higher rates of patients leaving the ED without
being seen. Measures of ED crowding varied across studies. CONCLUSIONS: ED
crowding is a major patient safety concern associated with poor patient outcomes.
Interventions and policies are needed to address this significant problem.
CLINICAL RELEVANCE: This review details the negative patient outcomes associated
with ED crowding. Study results are relevant to medical professionals and those
that seek care in the ED.
PMID- 24354887
TI - The role of Staphylococcal enterotoxin A in achieving oral tolerance to myelin
basic protein in adult mice.
AB - BACKGROUND: Oral tolerance is the biological process explaining the non
responsiveness of gut lymphoid tissue to intestinal content. Our study tested a
new approach for the enhancement of oral tolerance to a multiple sclerosis
triggering auto-antigen-myelin basic protein, by its oral administration with the
Staphylococcal enterotoxin A. METHODS: Immune tolerance thus stimulated was
assessed in adult BALB/c mice, by measuring different cytokines from the
supernatant of mesenteric lymph nodes cells (IFN-gamma, IL-4, IL-10, IL-17, and
TGF-beta), and in a SJL/E mouse model of experimental autoimmune
encephalomyelitis, by evaluating the development of regulatory T cells in
mesenteric lymph nodes and the clinical outcome of the intervention. RESULTS: We
obtained a significant rise in the levels of IL-10 and TGF-beta compared with
control and a significant decrease of IFN-gamma, IL-4 (p < 0.05). Regulatory T
cells were increased compared with control (p < 0.05). These results were
attributable both to myelin basic protein and to Staphylococcal enterotoxin A.
The clinical outcome of experimental autoimmune encephalomyelitis was influenced
only by the administration of myelin basic protein. CONCLUSION: In our
experiment, Staphylococcal enterotoxin A enhanced the immune tolerance to myelin
basic protein in the gut mucosa, but had no impact on the clinical evolution of
experimental autoimmune encephalomyelitis.
PMID- 24354888
TI - Examining how presumed media influence affects social norms and adolescents'
attitudes and drinking behavior intentions in rural Thailand.
AB - This study uses the influence of presumed media influence model as the
theoretical framework to examine how perceived social norms (i.e., descriptive,
subjective, and injunctive norms) will mediate the influence of pro- and
antidrinking media messages on adolescents' intention to consume alcohol in rural
Thailand. Data collected from 1,028 high school students indicate that different
mechanisms underlie drinking intentions between nondrinkers and those who have
consumed alcohol or currently drink. Among nondrinkers, perceived peer attention
to prodrinking messages indirectly influenced adolescents' prodrinking attitudes
and intentions to consume alcohol through all three types of perceived social
norms. Among drinkers, perceived peer attention to pro- and antidrinking messages
indirectly influenced adolescents' prodrinking attitudes and intentions to drink
alcohol through perceived subjective norm. The findings provide support for the
extended influence of presumed media influence model and have practical
implications for how antidrinking campaigns targeted at teenagers in Thailand
might be designed.
PMID- 24354889
TI - Relationship between inflammation and infliximab pharmacokinetics in rheumatoid
arthritis.
AB - AIMS: Infliximab, an anti-tumour necrosis factor-alpha monoclonal antibody, is
indicated in rheumatoid arthritis (RA). Our objective was to evaluate the
influence of the sources of infliximab pharmacokinetic variability in RA.
METHODS: Eighty-four patients treated with infliximab for RA were included in a
prospective noncomparative study. They were analysed between two consecutive
infliximab infusions. Infliximab concentrations were measured before the
infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next
infusion. Infliximab concentrations were described using a two-compartment
population pharmacokinetic model. RESULTS: The mean (interindividual standard
deviation) estimated central volume of distribution was 2.3 l (36%) and systemic
clearance was 0.019 l h(-1) (37%). The central volume of distribution increased
with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance
increased with pre-infusion C-reactive protein concentration by 20%, varying from
3 to 14 mg l(-) 1, and was decreased by 30% when methotrexate was coadministered.
CONCLUSIONS: The influence of methotrexate and inflammation on infliximab
clearance suggests that individual adjustment of infliximab doses according to
disease activity may be useful in RA.
PMID- 24354890
TI - A novel siderophore-independent strategy of iron uptake in the genus
Burkholderia.
AB - Like many other bacteria, Burkholderia sp. take up iron in its ferric form via
siderophore-dependent transporters. We observed that mutant strains of B.
cenocepacia H111 unable to synthesize siderophores did not exhibit any growth
defect under iron limited conditions. This finding suggested that this
opportunistic pathogen can adopt an alternative iron uptake strategy to
compensate for the loss of siderophores. We identified a putative iron uptake
locus, ftrBcc ABCD, in the genome of B. cenocepacia H111, which is also conserved
in other members of the genus Burkholderia. Mutants deficient in both siderophore
dependent and FtrBcc ABCD systems failed to grow under iron-limited conditions
and radiolabelled iron transport assays showed that these mutants were impaired
in iron uptake. In addition, expression of ftrBcc ABCD can restore growth of an
E. coli strain lacking all known high-affinity iron transport systems under iron
limited conditions. We show that all four proteins encoded by ftrBcc ABCD are
essential for iron uptake. Furthermore, our results indicate that the expression
of ftrBcc ABCD is regulated at the transcriptional level by iron concentration.
This study provides evidence of an alternative, siderophore-independent, iron
uptake system in Burkholderia species.
PMID- 24354891
TI - A two-phase study evaluating the relationship between Thimerosal-containing
vaccine administration and the risk for an autism spectrum disorder diagnosis in
the United States.
AB - BACKGROUND: Autism spectrum disorder (ASD) is defined by standardized criteria of
qualitative impairments in social interaction, qualitative impairments in
communication, and restricted and stereotyped patterns of behavior, interests,
and activities. A significant number of children diagnosed with ASD suffer a loss
of previously-acquired skills, which is suggestive of neurodegeneration or a type
of progressive encephalopathy with an etiological pathogenic basis occurring
after birth. To date, the etiology of ASD remains under debate, however, many
studies suggest toxicity, especially from mercury (Hg), in individuals diagnosed
with an ASD. The present study evaluated concerns about the toxic effects of
organic-Hg exposure from Thimerosal (49.55% Hg by weight) in childhood vaccines
by conducting a two-phased (hypothesis generating/hypothesis testing) study with
documented exposure to varying levels of Thimerosal from vaccinations. METHODS: A
hypothesis generating cohort study was undertaken to evaluate the relationship
between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus
acellular-Pertussis (DTaP) vaccine in comparison to a Thimerosal-free DTaP
vaccine administered, from 1998 through 2000, for the risk of ASD as reported in
the Vaccine Adverse Event Reporting System (VAERS) database (phase I). A
hypothesis testing case-control study was undertaken to evaluate the relationship
between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines
administered at specific intervals in the first six months of life among cases
diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine
Safety Datalink (VSD) database (phase II). RESULTS: In phase I, it was observed
that there was a significantly increased risk ratio for the incidence of ASD
reported following the Thimerosal-containing DTaP vaccine in comparison to the
Thimerosal-free DTaP vaccine. In phase II, it was observed that cases diagnosed
with an ASD were significantly more likely than controls to receive increased
organic-Hg from Thimerosal-containing hepatitis B vaccine administered within the
first, second, and sixth month of life. CONCLUSIONS: Routine childhood
vaccination is an important public health tool to reduce the morbidity and
mortality associated with infectious diseases, but the present study provides new
epidemiological evidence supporting an association between increasing organic-Hg
exposure from Thimerosal-containing childhood vaccines and the subsequent risk of
an ASD diagnosis.
PMID- 24354893
TI - Preparation and characterization of Compritol 888 ATO matrix tablets for the
sustained release of diclofenac sodium.
AB - The preparation of lipophilic matrix tablets for the sustained release of water
soluble drugs via direct compression is not always feasible due to poor flow and
rapid drug release. The aim was to evaluate the potential for developing
sustained-release diclofenac sodium tablets, using Compritol(r) 888 ATO as a
lipid matrix, by a wet granulation technique. The effects of wet granulation
method (planetary mixer and fluid-bed) and liquid binder type (HPMC Metolose(r)
603, 606 or 615) on weight uniformity, tensile strength and release rates were
investigated. The influence of compression force and speed during tablet
manufacture under simulated rotary press production conditions were also
evaluated. Rapid release of diclofenac sodium from directly compressed matrices
was observed. A wet granulation technique using different HPMC binders produced
free-flowing granules and matrices which released diclofenac sodium in a
sustained manner over several hours. When the formulation comprising the lowest
viscosity grade HPMC (Metolose(r) 603) was further evaluated using a laboratory
scale fluid-bed system, consistently sized granules with good flowability and
matrices with good weight uniformity and tensile strengths were produced. Release
rates were consistent over a range of compression speeds and forces indicating
the suitability of the formulation for production on a rotary tablet press.
PMID- 24354892
TI - Mechanistic insights into activation and SOCS3-mediated inhibition of
myeloproliferative neoplasm-associated JAK2 mutants from biochemical and
structural analyses.
AB - JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream
of cell surface receptor activation by cognate haemopoietic cytokines, including
erythropoietin and thrombopoietin. The pseudokinase domain (JH2) of JAK2
negatively regulates the catalytic activity of the adjacent tyrosine kinase
domain (JH1) and mutations within the pseudokinase domain underlie human
myeloproliferative neoplasms, including polycythaemia vera and essential
thrombocytosis. To date, the mechanism of JH2-mediated inhibition of JH1 kinase
activation as well as the susceptibility of pathological mutant JAK2 to
inhibition by the physiological negative regulator SOCS3 (suppressor of cytokine
signalling 3) have remained unclear. In the present study, using recombinant
purified JAK2JH1-JH2 proteins, we demonstrate that, when activated, wild-type and
myeloproliferative neoplasm-associated mutants of JAK2 exhibit comparable
enzymatic activity and inhibition by SOCS3 in in vitro kinase assays. SAXS (small
angle X-ray scattering) showed that JAK2JH1-JH2 exists in an elongated
configuration in solution with no evidence for interaction between JH1 and JH2
domains in cis. Collectively, these data are consistent with a model in which
JAK2's pseudokinase domain does not influence the activity of JAK2 once it has
been activated. Our data indicate that, in the absence of the N-terminal FERM
domain and thus cytokine receptor association, the wild-type and pathological
mutants of JAK2 are enzymatically equivalent and equally susceptible to
inhibition by SOCS3.
PMID- 24354894
TI - Met and unmet need for personal assistance among community-dwelling New
Zealanders 75 years and over.
AB - Ageing in place initiatives that aim to keep older people out of hospitals and
rest homes and in their own homes for longer have been at the forefront of aged
care policy since the early 1990s. The success of these policies depends largely
on the availability of a suitable home environment, a supportive social network
and regular assessment to detect changes in the older person's health status and
needs for support. The BRIGHT Trial was a randomised control trial investigating
the effectiveness of introducing case finding in primary care settings to detect
unmet need and risk of disability among older people. We used baseline
questionnaire data collected in 2008-2009 from 3753 community-dwelling older
people to estimate and describe use and need for additional personal assistance.
Logistic regression was used to identify the most important predictors of
reporting some need for support and unmet need. Eighty-one per cent of
participants required support with at least one instrumental activity of daily
living. Sixty-six per cent were meeting their needs with the support they were
currently receiving. Unmet need was most frequently reported for heavy housework
(65%) and light housework (53%). While spouses, family members and friends were
the main providers of support for light housework, meal preparation, shopping,
finances and transportation, paid staff most frequently provided personal care
and heavy housework assistance. Reporting mobility difficulty (OR = 3.5),
identifying as a care provider (OR = 1.7) and being female (OR = 1.9) were all
significant predictors of some need for assistance as well as unmet need for
assistance (OR = 2.5, 1.7 and 1.7 respectively). The findings highlight the
importance of regular needs assessment for older people living in the community
particularly, given the reliance on spousal support for the majority of
activities.
PMID- 24354895
TI - Delayed-onset pachyonychia congenita caused by a novel mutation in the V2 domain
of keratin 6b.
PMID- 24354896
TI - Mortality associated with burn injury - a cross sectional study from Karachi,
Pakistan.
AB - BACKGROUND: Burn injuries are a major cause of medico legal deaths in Pakistan.
The present study was conducted with the aim to assess the mortality rate related
to different types of burns injuries. FINDINGS: This was an observational
prospective cross sectional study conducted in Burns Ward of Civil Hospital,
Karachi during a period of two years from January 1st 2010 to December 31st,
2011. Data was collected over a questionnaire containing demographic variables as
well as date of burn, date of the death (if patient expired), total body surface
area involved, cause and manner of burn. The data was statistically analyzed by
SPSS v. 16. A total of 1979 patients were admitted to the department during the
study period. Out of them, 715 died, hence a mortality rate of 36.12%. Out of the
715 patients, 380 (53.1%) were males and 335 (46.9%) were females. Mortality was
highest in age-group 16-30 years (n = 395, 55.2%). Majority of the deaths were
accidental (n = 685, 95.8%). Fire burns was found to be the most common cause of
death (n = 639, 89.3%). 35% (n = 252) of the patients who died had more than 60%
of total body surface area involved in burns. CONCLUSION: Measures must be taken
to inform the general population of the possible causes of these injuries, and to
enable the people to be prepared to face any such circumstances.
PMID- 24354897
TI - PTSD and cognitive functioning: importance of including performance validity
testing.
AB - Many studies have observed an association between post-traumatic stress disorder
(PTSD) and cognitive deficits across several domains including memory, attention,
and executive functioning. The inclusion of response bias measures in these
studies, however, remains largely unaddressed. The purpose of this study was to
identify possible cognitive impairments correlated with PTSD in returning
OEF/OIF/OND veterans after excluding individuals failing a well-validated
performance validity test. Participants included 126 men and 8 women with a
history of mild traumatic brain injury (TBI) referred for a comprehensive
neuropsychological evaluation as part of a consortium of five Veterans Affairs
hospitals. The PTSD CheckList (PCL) and Word Memory Test (WMT) were used to
establish symptoms of PTSD and invalid performance, respectively. Groups were
categorized as follows: Control (PCL < 50, pass WMT), PTSD-pass (PCL >= 50, pass
WMT), and PTSD-fail (PCL >= 50, fail WMT). As hypothesized, failure on the WMT
was associated with significantly poorer performance on almost all cognitive
tests administered; however, no significant differences were detected between
individuals with and without PTSD symptoms after separating out veterans failing
the WMT. These findings highlight the importance of assessing respondent validity
in future research examining cognitive functioning in psychiatric illness and
warrant further consideration of prior studies reporting PTSD-associated
cognitive deficits.
PMID- 24354898
TI - The use of oral sildenafil for management of right ventricular dysfunction after
pediatric heart transplantation.
AB - High pulmonary vascular resistance index (PVRI) can lead to right ventricular
dysfunction and failure of the donor heart early after pediatric heart
transplantation. Oral pulmonary vasodilators such as sildenafil have been shown
to be effective modifiers of pulmonary vascular tone. We performed a
retrospective, observational study comparing patients treated with sildenafil
("sildenafil group") to those not treated with sildenafil ("nonsildenafil group")
after heart transplantation from 2007 to 2012. Pre- and posttransplant data were
obtained, including hemodynamic data from right heart catheterizations. Twenty
four of 97 (25%) transplant recipients were transitioned to sildenafil from other
systemic vasodilators. Pretransplant PVRI was higher in the sildenafil group (6.8
+/- 3.9 indexed Woods units [WU]) as compared to the nonsildenafil group (2.5 +/-
1.7 WU, p=0.002). In the sildenafil group posttransplant, there were significant
decreases in systolic pulmonary artery pressure, mean pulmonary artery pressure,
transpulmonary gradient and PVRI (4.7 +/- 2.9 WU before sildenafil initiation to
2.7 +/- 1 WU on sildenafil, p=0.0007). While intubation time, length of inotrope
use and time to hospital discharge were longer in the sildenafil group, survival
was similar between both groups. Oral sildenafil was associated with a
significant improvement in right ventricular dysfunction and invasive hemodynamic
measurements in pediatric heart transplant recipients with high PVRI early after
transplant.
PMID- 24354899
TI - A multicentre randomized controlled trial of an empowerment-inspired intervention
for adolescents starting continuous subcutaneous insulin infusion--a study
protocol.
AB - BACKGROUND: Continuous subcutaneous insulin infusion (CSII) treatment among
children with type 1 diabetes is increasing in Sweden. However, studies
evaluating glycaemic control in children using CSII show inconsistent results.
The distribution of responsibility for diabetes self-management between children
and parents is often unclear and needs clarification. There is much published
support for continued parental involvement and shared diabetes management during
adolescence. Guided Self-Determination (GSD) is an empowerment-based, person
centred, reflection and problem solving method intended to guide the patient to
become self-sufficient and develop life skills for managing difficulties in
diabetes self-management. This method has been adapted for adolescents and
parents as Guided Self-Determination-Young (GSD-Y). This study aims to evaluate
the effect of an intervention with GSD-Y in groups of adolescents starting on
insulin pumps and their parents on diabetes-related family conflicts, perceived
health and quality of life (QoL), and metabolic control. Here, we describe the
protocol and plans for study enrollment. METHODS/DESIGN: This study is designed
as a randomized, controlled, prospective, multicentre study. Eighty patients
between 12-18 years of age who are planning to start CSII will be included. All
adolescents and their parents will receive standard insulin pump training. The
education intervention will be conducted when CSII is to be started and at four
appointments in the first 4 months after starting CSII. The primary outcome is
haemoglobin A1c levels. Secondary outcomes are perceived health and QoL,
frequency of blood glucose self-monitoring and bolus doses, and usage of
carbohydrate counting. The following instruments will be used: Disabkids, 'Check
your health', the Diabetes Family Conflict Scale and the Swedish Diabetes
Empowerment Scale. Outcomes will be evaluated within and between groups by
comparing data at baseline, and at 6 and 12 months after starting treatment.
DISCUSSION: In this study, we will assess the effect of starting an CSII together
with the model of GSD to determine whether this approach leads to retention of
improved glycaemic control, QoL, responsibility distribution and reduced diabetes
related conflicts in the family.
PMID- 24354900
TI - Evaluation of the implementation of a bowel management protocol in intensive
care: effect on clinician practices and patient outcomes.
AB - AIMS AND OBJECTIVES: To evaluate the effect of a multifaceted implementation of a
bowel management protocol on outcomes for intensive care patients, in particular
the incidence of constipation and diarrhoea, and on clinicians' bowel management
practices. BACKGROUND: Complications associated with poor bowel management for
critically ill patients result in adverse outcomes. Implementation of protocols
requires strategies proven to change clinician behaviour. DESIGN: Before and
after study. METHODS: Our bowel management protocol was implemented using three
evidence-based elements: education sessions, printed educational materials in the
form of a fact sheet and reminders. We retrospectively collected data from
patients' medical records admitted at two time points within three Sydney
metropolitan intensive care units (preimplementation, n = 101;
postimplementation, n = 107). RESULTS: No significant difference was found in the
incidence of constipation and diarrhoea pre and postimplementation of the
protocol. Seventy-two per cent (n = 73) of patients preimplementation and 70% (n
= 75) of patients postimplementation experienced one or more episodes of
constipation (bowels not open for 72 hours or greater), and 16% (n = 16) of
patients preimplementation and 20% (n = 21) of patients postimplementation
experienced one or more episodes of diarrhoea. There was a slight nonsignificant
increase in bowel assessment on admission by medical officers postimplementation
(pre, 47%, n = 48; post, 60%, n = 64). CONCLUSION: Targeted multifaceted
implementation of a bowel management protocol did not have an impact on the
incidence of constipation or diarrhoea for intensive care patients or on
clinician practices. The lack of impact on patient outcomes may be due to
clinicians' nonadherence to our bowel management protocol. Reasons clinicians'
practices did not change may include the influences of clinical decision-making
on behaviour. RELEVANCE TO CLINICAL PRACTICE: This study highlights difficulties
inherent in changing clinician behaviour and practices to improve patient
outcomes despite using an evidence-based multifaceted implementation strategy.
Further research is required to ascertain the most effective implementation
strategies.
PMID- 24354901
TI - Associations of eating a late-evening meal before bedtime with low serum amylase
and unhealthy conditions.
AB - Little is known about the associations of eating a late-evening meal (ELM), a
putative unhealthy eating behavior, with low serum amylase, other eating
behaviors, and cardiometabolic risk factors. Therefore, we investigated whether
ELM before bedtime was associated with low serum amylase or other clinical
factors in 2,426 asymptomatic adults aged 20-80 years. Multivariate logistic
regression analysis showed that ELM was significantly associated with low serum
amylase (<60 IU/l), overweight, smoking, daily alcohol consumption, skipping
breakfast, and rapid eating, but not with abnormal glucose metabolism. In
conclusion, ELM may be independently associated with low serum amylase and common
unhealthy behaviors.
PMID- 24354902
TI - Indoor air quality and thermal comfort in temporary houses occupied after the
Great East Japan Earthquake.
AB - Thermal conditions and indoor concentrations of aldehydes, volatile organic
compounds (VOCs), and NO2 were investigated in 19 occupied temporary houses in 15
temporary housing estates constructed in Minamisoma City, Fukushima, Japan. The
data were collected in winter, spring, and summer in January to July 2012.
Thermal conditions in temporary log houses in the summer were more comfortable
than those in pre-fabricated houses. In the winter, the indoor temperature was
uncomfortably low in all of the houses, particularly the temporary log houses.
Indoor air concentrations for most aldehydes and VOCs were much lower than the
indoor guidelines, except for those of p-dichlorobenzene, acetaldehyde, and total
VOCs. The indoor p-dichlorobenzene concentrations exceeded the guideline (240
MUg/m(3)) in 18% of the temporary houses, and the 10(-3) cancer risk level (91
MUg/m(3)) was exceeded in winter in 21% due to use of moth repellents by the
occupants. Indoor acetaldehyde concentrations exceeded the guideline (48 MUg/m(3)
) in about half of the temporary houses, likely originating from the wooden
building materials. Indoor NO2 concentrations in the temporary houses were
significantly higher in houses where combustion heating appliances were used
(0.17 +/- 0.11 ppm) than in those where they were not used (0.0094 +/- 0.0065
ppm). PRACTICAL IMPLICATIONS: In the winter, log-house-type temporary houses are
comfortable in terms of humidity, dew condensation, and fungi based on the
results of questionnaires and measurements, whereas pre-fabricated temporary
houses are more comfortable in terms of temperature. In the summer, log-house
type temporary houses are comfortable in terms of temperature and humidity. More
comfortable temporary housing in terms of temperature and humidity year-round is
needed. Indoor air concentrations of p-dichlorobenzene and NO2 were quite high in
some temporary houses due to occupants' activities, such as use of moth
repellents and combustion heating appliances. The government should provide
recommendations for safe use of temporary houses by occupants.
PMID- 24354904
TI - Effect of body position on preterm newborns receiving continuous positive airway
pressure.
AB - AIM: To evaluate the effect of body position on the cardiorespiratory indicators
of preterm newborns receiving nasal continuous positive airway pressure (CPAP).
METHODS: Analytical, observational, prospective, cross-sectional, randomised
crossover study was carried out on sixteen newborns that received nasal CPAP. The
infants had a mean gestational age of 29.7 +/- 2 weeks and birthweight of 1353 +/
280 g. Cardiorespiratory indicators (respiratory rate, heart rate and oxygen
saturation) were evaluated in each infant in the supine, prone and right and left
lateral decubitus positions at intervals of 10 min over a period of 60 min.
RESULTS: The cardiorespiratory indicators were similar and within the normal
range in the four decubitus positions. There was no difference in respiratory or
heart rate between body positions. Although they showed desirable values, oxygen
saturation was significantly lower in left lateral decubitus (96.6 +/- 1.7%) when
compared to the supine (97.1 +/- 1.3%) and prone positions (97.4 +/- 1.1%) (p =
0.00) and was also significantly lower in right lateral decubitus (96.9 +/- 1.4%)
when compared to the prone position (p = 0.00). CONCLUSION: We found no
preferential decubitus position for preterm newborns receiving nasal CPAP, the
supine position may be a choice, but the left and right lateral positions were
less advantageous in terms of oxygen saturation.
PMID- 24354903
TI - Ethnobotanical survey of cooling herbal drinks from southern China.
AB - BACKGROUND: Liang cha ("cooling tea", "herbal tea" or "cool tisane" in Chinese)
are herbal drinks widely produced in southern China and consumed by billions of
people worldwide to prevent and treat internal heat as well as a range of
associated health conditions. Globalization and renewed interest in botanical
remedies has attracted growing attention in cooling herbal drinks by industry,
scientists and consumers. However, there is a knowledge gap on the plant species
used and commercialized for cooling herbal drinks in southern China and their
associated ethnobotanical use, habitat and conservation status. This is the first
study to document plant species used and commercialized as liang cha in southern
China's Lingnan region and associated ethnomedical function, preparation methods,
habitat and conservation status. METHODS: Three hundred market surveys were
conducted between 2010-2012 in the largest herbal drink producing region of China
to record plants used for liang cha and to document knowledge on their medicinal
function, habitat and conservation status. Product samples and voucher specimens
were collected for taxonomic identification. RESULTS: All informants harvest and
cultivate plants for preparing herbal drinks for their medicinal, cultural and
economic values. A total of 222 ethnotaxa corresponded to 238 botanical taxa
(species, varieties or subspecies) belonging to 86 families and 209 genera were
recorded as liang cha to treat health conditions in the study area. Recorded
remedies consisted of one or several plant species to treat conditions classified
into 27 major health conditions with clearing internal heat being the most common
medicinal function. The habitat types of plants documented for use as liang cha
include 112 wild harvested species, 51 species that are either wild harvested or
cultivated, 57 cultivated species, and 2 naturalized species. According to
China's Red List and CITES on conservation status, one of these species is
endangered, one species is critically endangered, eight species are vulnerable,
one is listed in CITES II, three are listed in Regional Red Data Book and the
remaining 224 species are in the least concerned conservation category.
CONCLUSIONS: The liang cha industry of southern China reflects the plant species
richness and cultural diversity of the region. Future research on safety and
efficacy of herbal drinks as well as ecological and cultural conservation efforts
are needed for the sustainable growth of China's botanical industry.
PMID- 24354905
TI - An update on the clinical development of proprotein convertase subtilisin kexin 9
inhibitors, novel therapeutic agents for lowering low-density lipoprotein
cholesterol.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an essential role in
the degradation of low-density lipoprotein C (LDL-C) receptors, and PCSK9
inhibitors have recently emerged as a potential treatment option to reduce LDL-C.
Our paper reviewed the current available Phase II clinical trials of PCSK9
inhibitors for the treatment of dyslipidemia. A second objective of this review
was to evaluate the potential clinical role of PCSK9 inhibitors in the management
of dyslipidemia. Studies evaluating the efficacy and safety of any PCSK9
inhibitors in patients with dyslipidemia were included. The monoclonal antibodies
REGN727/SAR236553 and AMG145 have the most published clinical data. Seven phase
II trials were retrieved that evaluated the efficacy and safety of
REGN727/SAR236553 or AMG145 in patients with either hypercholesterolemia or
heterozygous familial hypercholesterolemia (HeFH). These two agents significantly
decreased LDL-C levels either as monotherapy or in combination with other lipid
lowering agents. REGN727/SAR236553 and AMG145 have been well tolerated. The
ongoing phase III trials of these two agents are summarized. REGN727/SAR236553
and AMG145 have demonstrated the potential to further decrease LDL-C levels when
added to conventional lipid-lowering therapy. Morbidity and mortality data are
required to define their roles in clinical practice.
PMID- 24354907
TI - The site and nature of airway obstruction after lung transplantation.
AB - RATIONALE: The chronic rejection of lung allografts is attributable to
progressive small airway obstruction. OBJECTIVES: To determine precisely the site
and nature of this type of airway obstruction. METHODS: Lungs from patients with
rejected lung allografts treated by a second transplant (n = 7) were compared
with unused donor (control) lungs (n = 7) using multidetector computed tomography
(MDCT) to determine the percentage of visible airways obstructed in each airway
generation, micro-computed tomography (microCT) to visualize the site of
obstruction, and histology to determine the nature of this obstruction.
MEASUREMENTS AND MAIN RESULTS: The number of airways visible with MDCT was not
different between rejected and control lungs. However, 10 +/- 7% of observed
airways greater than 2 mm in diameter, 50 +/- 22% of airways between 1 and 2 mm
in diameter, and 73 +/- 10% of airways less than 1 mm in diameter were obstructed
in the rejected lungs. MicroCT confirmed that the mean lumen diameter of
obstructed airways was 647 +/- 317 MUm but showed no difference in either total
number and cross-sectional area of the terminal bronchioles or in alveolar
dimensions (mean linear intercept) between groups (P > 0.05). In addition,
microCT demonstrated that only segments of the airways are obstructed. Histology
confirmed a constrictive form of bronchiolitis caused by expansion of
microvascular-rich granulation tissue in some locations and collagen-rich scar
tissue in others. CONCLUSIONS: Chronic lung allograft rejection is associated
with a progressive form of constrictive bronchiolitis that targets conducting
airways while sparing larger airways as well as terminal bronchioles and the
alveolar surface.
PMID- 24354906
TI - Association study of angiotensin converting enzyme gene polymorphism with elderly
diabetic hypertension and lipids levels.
AB - OBJECTIVE: To investigate the relationship between angiotensin converting enzyme
(ACE) gene insertion/deletion (I/D) polymorphism and diabetic essential
hypertension in elderly population. METHODS: Polymerase chain reaction (PCR)
technique was used in 260 elderly normal control patients, 205 elderly
hypertensive patients and 138 elderly diabetic hypertensive patients to detect
the I/D polymorphism in ACE gene. RESULTS: DD genotype frequency (0.352) and D
allele frequency (0.543) in elderly hypertensive patients were higher than those
in the normal control patients. DD genotype (0.421) and D allele frequency
(0.579) in elderly diabetic hypertensive patients were significantly higher than
those in the control patients (0.133 and 0.250). The differences of DD genotype
and D allele frequency between the elderly hypertensive patients and the elderly
diabetic hypertensive patients were not significant (P > 0.05). CONCLUSION: ACE
gene deletion is a risk factor for hypertension but is not a risk factor for
diabetes in elderly population.
PMID- 24354908
TI - A novel personalized vaccine approach in combination with targeted therapy in
advanced renal cell carcinoma.
AB - The historical treatment paradigm for metastatic renal cell carcinoma has focused
on immunomodulatory agents, such as IFN-alpha and IL-2, which provide good
clinical outcomes in only a subset of patients. The development of therapies that
target the VEGF and mTOR pathways have significantly altered the treatment
landscape for this disease, with novel inhibitors providing substantial
improvements in progression-free and overall survival over previous standards of
care. Despite these advances, toxicity from targeted therapy and the development
of resistance results in disease progression. By contrast, vaccine-based
immunotherapy represents a promising new approach for the treatment of patients
with metastatic renal cell carcinoma; however, tumor-induced immunosuppression
has limited the clinical efficacy of this modality until recently. Some evidence
suggests that certain targeted therapies, such as sunitinib, may reduce this
immunosuppression and enhance the tumor microenvironment to promote synergy with
autologous dendritic cell vaccines.
PMID- 24354909
TI - Cutaneous diffuse large B-cell lymphoma, leg type, secondary to testicular
diffuse large B-cell lymphoma.
PMID- 24354910
TI - Regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by the LysR-type
regulator LeuO.
AB - LeuO is a quiescent LysR-type regulator belonging to the H-NS regulon. Activation
of leuO transcription represses expression of pathogenicity island 1 (SPI-1) in
Salmonella enterica serovar Typhimurium and inhibits invasion of epithelial
cells. Loss of HilE suppresses LeuO-mediated downregulation of SPI-1. Activation
of leuO transcription reduces the level of HilD protein, and loss of HilE
restores the wild type HilD level. Hence, LeuO-mediated downregulation of SPI-1
may involve inhibition of HilD activity by HilE, a view consistent with the fact
that HilE is a HilD inhibitor. In vivo analyses using beta-galactosidase fusions
indicate that LeuO activates hilE transcription. In vitro analyses by slot
blotting, electrophoretic mobility shift analysis and DNase I footprinting show
that LeuO binds the hilE promoter region. Although residual SPI-1 repression by
LeuO is observed in the absence of HilE, the LeuO-HilE-HilD 'pathway' appears to
be the major mechanism. Because both leuO and SPI-1 are repressed by H-NS,
activation of leuO transcription may provide a backup mechanism for SPI-1
repression under conditions that impair H-NS-mediated silencing.
PMID- 24354911
TI - Systemic therapy for atopic dermatitis.
AB - Systemic therapy for atopic dermatitis (AD) is indicated in patients with severe
disease refractory to adequate topical treatment. Currently available drugs aim
to decrease inflammation by suppressing and/or modulating immune responses and
thus may indirectly improve skin barrier function, resulting in a decrease in
clinical signs and symptoms in particular pruritus. Before considering systemic
treatment, patient adherence to topical treatment including skin care has to be
ensured. The selection of the drug depends on the disease severity, localization,
complications, concomitant diseases, and age of the patient, but also on their
availability and costs as well as the doctor's experience. Bearing in mind the
potential risk of resistance, systemic therapy with antibiotics should be
exclusively considered in clinically manifest infections such as in children.
Here, we review recently published clinical trials and case reports on systemic
therapy of pediatric and adult patients with AD to draw conclusions for clinical
practice. Although AD is a common disease, controlled clinical studies
investigating the efficacy of systemic drugs are scarce, except for cyclosporine,
which has been approved for the therapy of severe AD.
PMID- 24354912
TI - Diagnosis and treatment of pulmonary embolism: a multidisciplinary approach.
AB - The diagnosis of pulmonary embolism (PE) is frequently considered in patients
presenting to the emergency department or when hospitalized. Although early
treatment is highly effective, PE is underdiagnosed and, therefore, the disease
remains a major health problem. Since symptoms and signs are non specific and the
consequences of anticoagulant treatment are considerable, objective tests to
either establish or refute the diagnosis have become a standard of care.
Diagnostic strategy should be based on clinical evaluation of the probability of
PE. The accuracy of diagnostic tests for PE are high when the results are
concordant with the clinical assessment. Additional testing is necessary when the
test results are inconsistent with clinical probability. The present review
article represents the consensus-based recommendations of the Interdisciplinary
Association for Research in Lung Disease (AIMAR) multidisciplinary Task Force for
diagnosis and treatment of PE. The aim of this review is to provide clinicians a
practical diagnostic and therapeutic management approach using evidence from the
literature.
PMID- 24354913
TI - Vicious viruses and vigilant vaccines: effects of linguistic agency assignment in
health policy advocacy.
AB - Studying the effect of a fictitious policy editorial advocating mandatory
vaccination of youth against human papillomavirus (HPV), the authors hypothesized
that linguistic assignment of agency to HPV (e.g., "HPV preys on millions of
people") would increase perceptions of its severity, relative to a comparable
message that assigned agency to humans (e.g., "Millions of people contract HPV").
In addition, the authors predicted that HPV vaccines would be perceived as more
effective when agency was assigned to vaccination (e.g., "Vaccination guards
people") rather than to humans (e.g., "People guard themselves through
vaccination"). University students (N = 361) were randomly assigned to read one
of four versions of the editorial defined by a 2 *2 (Threat Agency * Immunization
Agency) factorial design and thereafter completed a questionnaire. When agency
was assigned to the virus or the vaccine, HPV was perceived as a more severe
threat, vaccination was perceived as more effective, and people were more in
favor of mandatory HPV vaccination. The authors concluded that linguistic agency
assignment bestows potency to the agent, thereby making threats more alarming and
medical interventions seem more effective.
PMID- 24354914
TI - NQO1 rs1800566 C>T polymorphism was associated with a decreased risk of
esophageal cancer in a Chinese population.
AB - BACKGROUND. Esophageal cancer was the fifth most commonly diagnosed cancer and
the fourth leading cause of cancer-related death in China in 2009. Esophageal
squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers.
Genetic factors may play an important role in the carcinogenesis of ESCC.
METHODS. We conducted a hospital-based case-control study to evaluate functional
NAD(P)H: quinone oxidoreductase 1 (NQO1) rs1800566 C>T and NQO2 rs2070999 G>A
single-nucleotide polymorphisms on the risk of ESCC. A total of 629 patients with
ESCC and 686 controls were recruited for this study. The genotypes were
determined using the ligation detection reaction method. RESULTS. When the NQO1
rs1800566 CC homozygote genotype was used as the reference group, the TT genotype
was associated with a significantly decreased risk of ESCC. In the recessive
model, when the NQO1 rs1800566 CC/CT genotypes were used as the reference group,
the TT homozygote genotype was associated with a 31% decreased risk of ESCC. A
significantly decreased risk of ESCC was evident in patients with the NQO1
rs1800566 C>T polymorphism among females, those of a younger age (<63 years),
those who had never smoked, those who consumed alcohol and those who did not.
There was no association found between the NQO2 rs2070999 G>A polymorphism and
ESCC risk. CONCLUSION. The NQO1 rs1800566 TT genotype was associated with a
decreased risk of ESCC in a Chinese population. The association was evident among
female patients, younger patients, patients who had never smoked, patients who
consumed alcohol and those who did not. These findings need to be confirmed by
repeating the study in a larger cohort of patients.
PMID- 24354916
TI - Recombinant albumin monolayers on latex particles.
AB - The adsorption of recombinant human serum albumin (rHSA) on negatively charged
polystyrene latex micro-particles was studied at pH 3.5 and the NaCl
concentration range of 10(-3) to 0.15 M. The electrophoretic mobility of latex
monotonically increased with the albumin concentration in the suspension. The
coverage of adsorbed albumin was quantitatively determined using the depletion
method, where the residual protein concentration was determined by electrokinetic
measurements and AFM imaging. It was shown that albumin adsorption was
irreversible. Its maximum coverage on latex varied between 0.7 mg m(-2) for 10(
3) M NaCl to 1.3 mg m(-2) for 0.15 M NaCl. The latter value matches the maximum
coverage previously determined for human serum albumin on mica using the
streaming potential method. The increase in the maximum coverage was interpreted
in terms of reduced electrostatic repulsion among adsorbed molecules. These facts
confirm that albumin adsorption at pH 3.5 is governed by electrostatic
interactions and proceeds analogously to colloid particle deposition. The
stability of albumin monolayers was measured in additional experiments where
changes in the latex electrophoretic mobility and the concentration of free
albumin in solutions were monitored over prolonged time periods. Based on these
experimental data, a robust procedure of preparing albumin monolayers on latex
particles of well-controlled coverage and molecule distribution was proposed.
PMID- 24354915
TI - Israeli nurses' intention to report for work in an emergency or disaster.
AB - PURPOSE: This study investigates the effect of personal characteristics and
organizational factors on nurses' intention to report for work in a national
emergency. DESIGN: A convenience sample was drawn of 243 Israeli registered
nurses. A structured self-administered questionnaire collected data on (a)
intention to report for work, (b) barriers preventing nurses from reporting for
work, (c) perceived self-efficacy in emergency conditions, (d) risk appraisal of
health hazards, (e) knowledge of nurses' roles in emergency work, (f) access to
institutional support services, and (g) reporting to work in a past emergency.
METHODS: Data were analyzed by descriptive statistics, Pearson correlation
coefficients, t tests, and multiple regression analysis. FINDINGS: Less than half
of the nurses who said they had been asked to report for work in a past emergency
had actually done so. The major barrier to reporting for work was childcare
demands. There was a significant correlation between perceived knowledge, risk
appraisal, self-efficacy, and intention to report. Self-efficacy, risk appraisal,
working through an earlier emergency, perceived knowledge, and full or part-time
working altogether. CONCLUSIONS: Personal factors, such as perceived knowledge,
risk appraisal, and self-efficacy, are more important to Israeli nurses than
objective barriers in preventing them from reporting for emergency work. The
level of perceived knowledge as to the demands on and duties of nurses in a large
scale emergency is low. Self-efficacy enhancing activities need to be introduced
into nurse training for emergency preparedness. CLINICAL RELEVANCE: This study
makes an important contribution to research on the importance of perceived self
efficacy in the context of disaster planning.
PMID- 24354917
TI - Judging words by their covers and the company they keep: probabilistic cues
support word learning.
AB - Statistical learning may be central to lexical and grammatical development. The
phonological and distributional properties of words provide probabilistic cues to
their grammatical and semantic properties. Infants can capitalize on such
probabilistic cues to learn grammatical patterns in listening tasks. However,
infants often struggle to learn labels when performance requires attending to
less obvious cues, raising the question of whether probabilistic cues support
word learning. The current experiment presented 22-month-olds with an artificial
language containing probabilistic correlations between words' statistical and
semantic properties. Only infants with higher levels of grammatical development
capitalized on statistical cues to support learning word-referent mappings. These
findings suggest that infants' sensitivity to correlations between sounds and
meanings may support both word learning and grammatical development.
PMID- 24354918
TI - Intratumoral heterogeneity of genomic imbalance in a case of epithelioid
glioblastoma with BRAF V600E mutation.
AB - Epithelioid glioblastoma is among the rarest variants of glioblastoma and is not
formally recognized in the World Health Organization classification; it is
composed of monotonous, discohesive sheets of small, round cells with eccentric
nuclei and eosinophilic cytoplasm devoid of cytoplasmic stellate processes,
showing the retention of nuclear staining of INI-1 protein. Here, we report a
case involving a 22-year-old man with a right occipital lobe tumor, which
comprised mainly epithelioid tumor cells with a small area of diffusely
infiltrating less atypical astrocytoma cells showing a lower cell density. Array
comparative genomic hybridization separately performed for each histologically
distinct component demonstrated eight shared copy number alterations (CNAs) and
three CNAs observed only in epithelioid cells; one of the latter was a homozygous
deletion of a tumor suppressor gene, LSAMP, at 3q13.31. BRAF V600E mutation was
observed both in epithelioid tumor cells and in diffusely infiltrating less
atypical astrocytoma cells. Our findings suggest that the regional loss of LSAMP
led to the aggressive nature of epithelioid cells in the present case of
epithelioid glioblastoma.
PMID- 24354919
TI - Relationship between prosthodontic status and nutritional intake in the elderly
in Korea: National Health and Nutrition Examination Survey (NHANES IV).
AB - OBJECTIVES: Many health issues have been reported to be associated with poor
nutritional status. We sought to examine the association between nutritional
intake and oral health status in elderly people. METHODS: The association between
perceived disability in mastication and prosthodontic status was analysed using
multiple logistic regression. Multiple linear regression was used to analyse the
association between prosthodontic status and nutritional intake. RESULTS: The
elderly subjects with partial or full dentures reported chewing difficulties 1.62
fold more frequently (95% CI: 1.06-2.49) than those with natural teeth or a fixed
prosthesis after adjusting for gender, TMD (temporomandibular disorder),
household income and education level. Additionally, daily nutritional intakes of
energy, protein, fat, ash, calcium, phosphorus and thiamine were decreased
significantly in elderly with partial or full dentures compared with those with
no prosthesis or with a fixed prosthesis (P < 0.05). CONCLUSIONS: Our findings
underline oral health status and perceived disability in mastication are
associated with dietary imbalances in the elderly. We suggest that the evaluation
of patients' nutritional status should be considered as a part of an overall plan
for dental hygiene care.
PMID- 24354920
TI - Is it tea time for portal hypertension?
AB - Portal hypertension is the main complication of cirrhosis and represents a
leading cause of death in patients with chronic liver disease. Therapeutic agents
to improve portal hypertension should ameliorate the underlying mechanisms of
portal hypertension: the elevated hepatic resistance and the hyperdynamic
circulation. In the present issue of Clinical Science, Hsu and co-workers show
the beneficial effects of GTPs (green tea polyphenols) in improving portal
hypertension. Long-term administration of GTPs inhibited the development of
cirrhosis and portal hypertension by decreasing both hepatic resistance and
splanchnic hyperdynamic circulation. The main underlying mechanism of the
benefits of GTPs appears related to the down-regulation of splanchnic
angiogenesis. The present study adds further evidence supporting the potential of
natural compounds for an effective nutriceutical approach to the treatment of
patients with cirrhosis of the liver.
PMID- 24354922
TI - First observation of African tigerfish Hydrocynus vittatus predating on barn
swallows Hirundo rustica in flight.
AB - A population of African tigerfish Hydrocynus vittatus from the Schroda Dam,
actively prey on barn swallows Hirundo rustica in flight. This behaviour was
discovered during a radio telemetry study and documented using a motion picture
video camera. These results show that an avivorous diet is a part of the feeding
biology of H. vittatus, and may occur in other populations.
PMID- 24354921
TI - The effect of pre-travel advice on sexual risk behavior abroad: a systematic
review.
AB - BACKGROUND: Travelers often have casual sex abroad and the risk of acquiring a
sexually transmitted infection (STI) associated with casual travel sex is
considered to be threefold higher compared to the risk of casual sex in the home
country. Consequently, international guidelines recommend including STI advice in
the pre-travel consultation. We performed a systematic review on the effect of a
pre-travel STI intervention on sexual risk behavior abroad. METHODS: In September
2012, a systematic analysis and meta-analysis of peer reviewed literature were
performed on the relation between pre-travel STI advice for travelers and sexual
risk behavior abroad. Primary outcome measure consisted of the number of
travelers with a new sexual partner abroad; secondary outcome measure entailed
the proportion of consistent condom use. RESULTS: Six studies were identified for
inclusion in the review, of which three clinical trials on the effect of a
motivational intervention compared to standard pre-travel STI advice qualified
for the meta-analysis. Two of these trials were performed in US marines deployed
abroad and one in visitors of a travel clinic. The extensive motivational
training program of the marines led to a reduction in sexual risk behavior, while
the brief motivational intervention in the travel clinic was not superior to
standard advice. The meta-analysis established no overall effect on risk behavior
abroad. No clinical trials on the effect of a standard pre-travel STI discussion
were found, but a cohort study reported that no relation was found between the
recall of a nonstructured pre-travel STI discussion and sexual risk behavior,
while the recall of reading the STI information appeared to be related to more
consistent condom use. CONCLUSIONS: Motivational pre-travel STI intervention was
not found to be superior to standard STI advice, while no clinical trials on the
effect of standard pre-travel STI advice were found.
PMID- 24354923
TI - Hormonal and behavioral changes induced by acute and chronic experimental
infestation with Psoroptes cuniculi in the domestic rabbit Oryctolagus cuniculus.
AB - BACKGROUND: Parasitic diseases are important in animal production because they
cause high economic losses. Affected animals often exhibit stereotypical
behavioral alterations such as anorexia and inactivity, among others. Among the
diseases that commonly affect domestic rabbits is mange, which is caused by the
mite Psoroptes cuniculi. Therefore, within the context of the host-parasite
relationship, it is critical to understand the mechanisms involved in the
alteration of host behavior, in order to better utilize sick animal behavior as a
strategy for diagnosis and treatment of disease. METHODS: Rabbits were infested
placing mites in the ear conduct. We characterized changes in exploratory
behavior and scent marking evoked by acute (1-9 days) and chronic (25-33 days)
experimental infestation. Behavior was recorded during ten minutes while the
animals were in a 120 cm * 120 cm open field arena divided into 9 squares. Serum
cortisol was measured individually using radioimmunoassay kits. Locomotor
activity, chinning, rearing and body weight were compared using a Friedman test,
the effect of treatment (infested versus non-infested) across time was analyzed
using a repeated measures ANOVA, and the Pearson test was used to determine
whether chinning and ambulation scores were significantly correlated. Serum
cortisol levels and food consumption were analyzed with a Kruskal-Wallis test and
body temperature was analyzed with an ANOVA test. RESULTS: We observed a
significant decrease in rearing behavior as early as two days post-infestation,
while chinning and locomotor activity were significantly decreased four days post
infestation. Chronic infestation was associated with decreased food intake,
significant weight loss, and a trend toward increased serum cortisol levels,
while no changes were observed in body temperature. CONCLUSIONS: The presence of
visible lesions within the ear canal is commonly used to detect mite infestation
in rabbits, but this is possible only after chronic infestation. The behaviors
described here may be a useful and economic tool in guiding the early diagnosis
of parasitic infestation by P. cuniculi, allowing for early treatment and the
application of control measures before significant weight loss occurs, thereby
avoiding economic losses.
PMID- 24354924
TI - Knockdown of tropomyosin-related kinase B receptor expression in the nucleus
accumbens shell prevents intermittent social defeat stress-induced cross
sensitization to amphetamine in rats.
AB - The nucleus accumbens (NAc) is a critical brain region for the rewarding effects
of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress
and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF
containing projections to the NAc originate from the ventral tegmental area (VTA)
and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase
B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the
NAc shell during social defeat stress-induced cross-sensitization to amphetamine.
Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV
shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas
AAV-GFP (green fluorescent protein) was used as the control virus. Rats were
exposed to intermittent social defeat stress or handling procedures; amphetamine
challenge was given at 10 days after the last defeat and locomotor activity was
measured. Stressed rats that received the control virus showed cross
sensitization to amphetamine compared with the handled rats. In contrast, NAc
TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB
knockdown in the NAc was found to reduce the level of phospho-extracellular
signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented
stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1)
subunit of AMPA receptor in the VTA, as well as DeltaFosB expression in the NAc.
These findings indicated that BDNF-TrkB signaling in the NAc shell was required
for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling
also appeared to be involved in the regulation of GluA1 in the VTA, as well as in
the NAc DeltaFosB accumulation that could trigger cross-sensitization after
social defeat stress.
PMID- 24354926
TI - Plasma in dentistry: a review of basic concepts and applications in dentistry.
AB - OBJECTIVE: Plasma-related technologies are essential in modern industries.
Recently, plasma has attracted increased attention in the biomedical field. This
paper provides a basic knowledge of plasma and a narrative review of plasma
applications in dentistry. MATERIALS AND METHODS: To review plasma applications
in dentistry, an electronic search in PubMed, SCOPUS and Google scholar up to
December 2012 was done. This was followed by extensive hand searching using
reference lists from relevant articles. CONCLUSION: There have been attempts to
apply plasma technology in various fields of dentistry including surface
modifications of dental implants, adhesion, caries treatment, endodontic
treatment and tooth bleaching. Although many studies were in early stages, the
potential value of plasma for dental applications has been demonstrated. To
enlarge the scope of plasma applications and put relevant research to practical
use, interdisciplinary research with participation of dental professionals is
required.
PMID- 24354925
TI - Domestic exposure to fungal allergenic particles determined by halogen
immunoassay using subject's serum versus particles carrying three non-fungal
allergens determined by allergen-specific HIA.
AB - Studies that estimate indoor aeroallergen exposure typically measure a pre
selected limited range of allergens. In this study, inhalable aeroallergen
particles were quantified using the halogen immunoassay (HIA) to determine the
contribution of fungal and non-fungal aeroallergens to total allergen exposure.
Bioaerosols from 39 homes of fungal-allergic subjects were sampled using
inhalable fraction samplers and immunostained by HIA using resident subject's
immunoglobulin E (IgE) to detect allergen-laden particles. Fungal aerosols as
well as particles carrying mite, cat, and cockroach allergens were identified and
enumerated by HIA. Reservoir dust-mite (Der p 1), cat (Fel d 1), and cockroach
(Bla g 1) allergen concentrations were quantified by ELISA. Fungal particles that
bound subject's IgE in the HIA were 1.7 (bedroom)- and 1.4 (living room)-fold
more concentrated than Der p 1, Fel d 1, and Bla g 1 allergen particles combined.
Predominant fungal conidia that bound IgE were derived from common environmental
genera including Cladosporium and other fungi that produce amerospores. Airborne
mite, cat, and cockroach allergen particle counts were not associated with
reservoir concentrations determined by ELISA. This study demonstrates that
inhalable fungal aerosols are the predominant aeroallergen sources in Sydney
homes and should be considered in future exposure assessments. PRACTICAL
IMPLICATIONS: Indoor allergen exposure assessment studies have primarily focused
on a limited range of allergen sources in samples derived from reservoir dust
samples. Using an innovative immunodiagnostic approach, this study demonstrates
that fungal bioaerosols are the dominant source of aeroallergen exposure in the
domestic environment, providing unique insight into domestic aeroallergen
exposure.
PMID- 24354927
TI - The effect of surface treatment and bonding procedures on the bond strength of
silorane composite repairs.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of surface treatments
and adhesive protocols on the microtensile bond strength of a low-shrinkage
composite repair. MATERIALS AND METHODS: Ninety-six blocks of composite resin
Filtek LS were prepared using a half-hourglass-shaped silicone matrix. The
specimens were storage for 24 h in distilled water and were randomly divided into
the experimental (6) and negative control (2) groups (n = 12) according to the
surface treatment (diamond bur and aluminum oxide sandblasting) and adhesive
protocol (none; Filtek LS adhesive; phosphoric acid + Filtek LS adhesive; and
phosphoric acid + silane + Filtek LS adhesive). After the adhesive procedure, the
specimens were fixed in an hourglass-shaped silicone matrix and the other half of
the specimen was restored. Hourglass shaped specimens (n = 12) were used as
positive control (cohesive strength of the resin). The microtensile bonding test
was performed at a crosshead speed of 0.5 mm/min. The data were analyzed using
ANOVA, Tukey's and Dunnett's tests (alpha = 0.05). RESULTS: The bond strength
values were similar for all experimental groups, except the groups without
adhesive application. None of the experimental groups presented results similar
to the positive control group. CONCLUSIONS: The repair of silorane restorations
is viable; nevertheless, the different bonding procedures tested were incapable
to produce bond strengths similar to the cohesive strength of the material.
PMID- 24354928
TI - Evaluation of the safety of a combination of oral administration of
phenylbutazone and firocoxib in horses.
AB - Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific
NSAID has not been previously reported in horses. The goal of this study was to
determine the safety of a 10-day dosage regimen of phenylbutazone and firocoxib,
both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg
of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses
were assessed daily for changes in behavior, appetite, fecal consistency, signs
of abdominal pain, and oral mucous membrane ulceration. Horses were assessed
prior to and on the last day of treatment for changes in serum creatinine,
albumin, total protein, and urine-specific gravity. Horses underwent endoscopic
examination of the esophagus, stomach, and pylorus prior to and 24 hours after
the last treatment. A significant change in serum creatinine and total protein
was observed on day 10 of treatment. No other significant findings were noted
during the experiment. Results indicated that co-administration of phenylbutazone
and firocoxib may cause renal disease.
PMID- 24354929
TI - The effect of simvastatin-ezetimibe combination therapy on adipose tissue
hormones and systemic inflammation in patients with isolated
hypercholesterolemia.
AB - BACKGROUND: Pleiotropic effects of ezetimibe have only been investigated in a few
studies. The aim of this article was to compare the effects of simvastatin and
the combined treatment with simvastatin and ezetimibe on low-grade systemic
inflammation and plasma levels of selected adipokines in patients with isolated
hypercholesterolemia. METHODS: The study included 69 patients with elevated
cholesterol levels, who were allocated to one of the three groups treated for 12
weeks, respectively, with simvastatin (40 mg daily), simvastatin (40 mg daily)
plus ezetimibe (10 mg daily), or placebo. Plasma levels of lipids,
apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin,
tumor necrosis factor-alpha (TNF-alpha), free fatty acids (FFA), and high
sensitive C-reactive protein (hsCRP) were determined on the allocation day and
after 12 weeks of therapy. RESULTS: Apart from improving lipid profile,
simvastatin administered alone or in combination with ezetimibe, decreased plasma
levels of hsCRP, FFA, leptin, visfatin, and TNF-alpha, as well as increased
plasma levels of adiponectin. The combination therapy was superior to simvastatin
in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated
adipokines. The effect of the combination therapy, but not of simvastatin, on
systemic inflammation and plasma adipokines was stronger in insulin-resistant
than in insulin-sensitive subjects. CONCLUSIONS: The obtained results suggest
that insulin-resistant patients with hypercholesterolemia and high cardiovascular
risk may benefit the most from the combined treatment with simvastatin and
ezetimibe.
PMID- 24354930
TI - Effectiveness of an e-learning tool for education on pressure ulcer evaluation.
AB - AIMS AND OBJECTIVES: To evaluate the effectiveness of information and
communication technologies in the undergraduate students' pressure ulcer training
as a learning tool, compared with traditional teaching methods. BACKGROUND:
Pressure ulcers constitute one of the great challenges faced by nursing
professionals. Currently, pressure ulcer training is based on traditional on
campus teaching, involving lecture-style classes with frequent use of photographs
of the wounds. This traditional training has some important weaknesses that can
put the efficacy of the training at risk. DESIGN: A randomised controlled trial
was developed including undergraduate nursing students. METHODS: The intervention
group used an adaptive self-learning e-learning tool developed by the research
team (ePULab) for pressure ulcer assessment and treatment. The control group
received a traditional on-campus class on the same topic. Pretest and post-test
questionnaires were designed to assess the students' ability in pressure ulcer
diagnosis and treatment. RESULTS: The educational intervention based on the use
of the ePULab tool produced significantly better learning acquisition results
than those obtained by traditional lecture-style classes: the total score
improved in the control group from 8.23 (SD 1.23)-11.6 (SD 2.52) after the
lecture, whereas in the intervention group, the knowledge score changed from 8.27
(SD 1.39)-15.83 (SD 2.52) (p = 0.01) with the use of ePULab. CONCLUSIONS: The
results show a higher effectiveness of the devised e-learning approach for
education on management of pressure ulcers. RELEVANCE TO CLINICAL PRACTICE: Our
results reveal the suitability of the ePULab e-learning tool as an effective
instrument for training on assessment of and treatment for pressure ulcers and
its potential impact on clinical decision-making.
PMID- 24354931
TI - Predisposing factors for recurrence of HBV-related small hepatocellular carcinoma
after percutaneous radiofrequency ablation.
AB - BACKGROUND. Radiofrequency ablation (RFA) as a curative therapy for
hepatocellular carcinoma (HCC) is widely used. The aim of this study was to
investigate predisposing factors for HCC recurrence in patients with hepatitis B
virus (HBV)-related small HCC after RFA. METHods. A total of 170 patients
underwent percutaneous RFA for HBV-related small HCC (<=3 cm in diameter) from
January 2008 to December 2010 at Samsung Medical Center. We analyzed the risk
factors for recurrence of HCC after RFA. RESULTS. The median follow-up duration
was 27.0 months. A total of 89 patients (52%) experienced recurrence after
percutaneous RFA. Cumulative recurrence-free rates after RFA at 1-, 3-, and 5
years were 81.3%, 47.2% and 35.7%, respectively. Univariate analysis showed that
predisposing factors for HCC recurrence were the multinodularity (hazard ratio
(HR) 2.22, p = 0.005), pre-RFA HBV DNA levels >=2000 IU/mL (HR 1.61, p = 0.025),
and Barcelona Clinic Liver Cancer stage A (HR 1.54, p = 0.046). The independent
risk factors for recurrence by multivariate analysis were the multinodularity (HR
1.94, p = 0.026) and pre-RFA HBV DNA levels >=2000 IU/mL (HR 1.57, p = 0.039).
CONCLUSION. Multinodularity and HBV DNA levels were associated with the
recurrence of HBV-related small HCC after RFA.
PMID- 24354932
TI - Immunisation coverage among a birth cohort of Aboriginal infants in an urban
community.
AB - AIM: The aim of this study is to examine the age-appropriate immunisation
coverage and the factors associated with this in a cohort of Aboriginal infants
in an outer urban Sydney community in comparison with non-Aboriginal infants in
this community. METHODS: Data on immunisation coverage were extracted from the
Australian Childhood Immunisation Register for a birth cohort of 178 Aboriginal
and 356 non-Aboriginal infants born in Campbelltown between October 2005 and May
2007. Non-Aboriginal infants were matched on birthdates and gender. Data on
maternal socio-economic and other characteristics were collected by
questionnaire. RESULTS: Australian Childhood Immunisation Register records were
identified for 92% of infants. Immunisation rates of Aboriginal infants were
comparable with those of non-Aboriginal infants except for delay at 4 and 6
months. Rates of delay in immunisation at 12 and 18 months for both Aboriginal
and non-Aboriginal infants were similar. Young maternal age and higher parity
were both associated with a greater likelihood of delay. CONCLUSIONS:
Immunisation rates in this population of Aboriginal infants are comparable to
those of non-Aboriginal infants except for delay in immunisation at 4 and 6
months. Identified risk factors for both Aboriginal and non-Aboriginal infants
may be amenable to intervention. Strategies to ensure timely compliance with
immunisation schedules in this outer urban community have achieved reasonable
immunisation coverage for Aboriginal and non-Aboriginal infants.
PMID- 24354933
TI - Quality of life in people with diabetes: a systematic review of studies in Iran.
AB - Evaluation of health-related quality of life (HRQoL) among people with diabetes
has been growing in Iran over the last decade. The main aim of the current study
was to systematically review the characteristics of these studies and examine
quality of their findings. Persian (SID, Magiran) and English (Pubmed, Medline,
Web of Science, CINAHL, Scopus, PsycINFO and ERIC) databases were systematically
searched using the search terms: "diabetes" AND "quality of life" AND "Iran". The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines were followed. A total of 46 studies passed the inclusion criteria and
were included in the review. The included studies were conducted in 20 out of 30
provinces of the country. Most studies investigated HRQoL among people with type
2 diabetes. The Short Form Health Survey (SF-36) and WHO quality of life
instruments (WHOQOL) were the main instruments used in these studies. Studies
showed that people with diabetes had lower HRQoL than people without diabetes.
Better socioeconomic status and better control of cardiovascular risk factors
were associated with better HRQoL among the patients with diabetes. In general,
the predictors of HRQoL among Iranian patients were similar to their
international counterparts implying that diabetes patients share many common
features. The reviewed studies suffer from major methodological and reporting
flaws which limit validity and generalizability of their findings.
PMID- 24354935
TI - Provision of dental care in aged care facilities NSW Australia- Part 2 as
perceived by the carers (care providers).
AB - OBJECTIVES: To investigate carers' perception of the provision of dental care in
aged care facilities (ACFs) New South Wales (NSW), Australia. BACKGROUND: Carers
are responsible for 'hands-on, day-to-day' care of residents, including dental
care, yet there were no specific figures available concerning their role in NSW
ACFs. MATERIALS AND METHODS: Questionnaires were mailed to 406 NSW directors of
nursing (DONs) requesting completion by a carer who was proficient in English and
without the influence of the DON. The 23-item questionnaire was presented in 4
sections, and the data qualitatively analysed. RESULTS: 211 questionnaires were
completed and returned, giving a response rate of 52%. Carers were mostly female
(91.9%) in the 40-50 and >50 age groups. Oral health training had been received
by 66.7% of carers, and although 73.2% thought that their training was adequate,
carers in general requested further training. Long waiting periods for government
dental services (69.4%) and resident unable to communicate oral health problems
(69.2%) were seen as the most frequent barriers to dental care. Almost all carers
reported the availability of electric tooth brushes, fluoride gel, disclosing
tablets/gel, interdental brushes and the use of a foam mouth prop, while few
reported the use of other dental care products. CONCLUSION: As carers provided
almost all of oral health care for residents, emphasis should be placed on
training in geriatric dental care techniques and use of dental products.
PMID- 24354934
TI - Changes in serum immunomolecules during antibiotic therapy for Mycobacterium
avium complex lung disease.
AB - Little information is available regarding changes in immune status for patients
with Mycobacterium avium complex (MAC) lung disease during antibiotic therapy.
Serum immunomolecules from 42 patients with MAC lung disease were assayed
comparatively using an array-based system according to (i) patients with MAC lung
disease at the time of diagnosis versus healthy controls and (ii) alterations
after 12 months of antibiotic therapy in the MAC lung disease group. In addition,
cytokine analyses were performed to determine whether cytokine responses were
associated specifically with the disease phenotype, treatment outcome and
aetiological agent. Notably, the serum concentrations of type 1 cytokine
associated molecules, such as CD40L, interferon (IFN)-gamma, interleukin (IL)-8
and IL-23, were decreased significantly in patients at the time of diagnosis,
suggesting that these molecules may serve as indicators of host susceptibility to
MAC disease. Although the overall serum level of T helper type 1 (Th1)-related
molecules, such as CD40L and IFN-gamma, was restored after treatment, Th17
related cytokines, such as IL-17 and IL-23, were down-regulated significantly at
12 months post-treatment compared to pretreatment. Furthermore, these cytokine
patterns differed among patient subgroups. Decreased serum concentrations of IL
17 and/or IL-23 were associated with failure of sputum conversion, the
fibrocavitary disease phenotype and M. intracellulare lung disease. Thus, the
reciprocal balance between Th1 and Th17 immunity during antibiotic therapy for
MAC lung disease is critical for dictating the treatment response. In conclusion,
a low level of Th1-related immunomolecules may perpetuate MAC lung disease, and
the serum concentrations of Th17-related cytokines can reflect the treatment
outcome, disease phenotype and aetiological agent.
PMID- 24354936
TI - Multivariate evaluation of the effectiveness of treatment efficacy of
cypermethrin against sea lice (Lepeophtheirus salmonis) in Atlantic salmon (Salmo
salar).
AB - BACKGROUND: The sea louse Lepeophtheirus salmonis is the most important
ectoparasite of farmed Atlantic salmon (Salmo salar) in Norwegian aquaculture.
Control of sea lice is primarily dependent on the use of delousing
chemotherapeutants, which are both expensive, and toxic to other wildlife. The
method most commonly used for monitoring treatment effectiveness relies on
measuring the percentage reduction in the mobile stages of Lepeophtheirus
salmonis only. However, this does not account for changes in the other sea lice
stages and may result in misleading or incomplete interpretation regarding the
effectiveness of treatment. With the aim of improving the evaluation of delousing
treatments, we explored multivariate analyses of bath treatments using the
topical pyrethroid, cypermethrin, in salmon pens at five Norwegian production
sites. RESULTS: Conventional univariate analysis indicated reductions of over 90%
in mobile stages at all sites. In contrast, multivariate analyses indicated
differing treatment effectiveness between sites (p-value < 0.01) based on changes
in the proportion and abundance of the chalimus and PAAM (pre-adult and adult
males) stages. Low water temperatures and shortened intervals between sampling
after treatment may account for the differences in the composition of chalimus
and PAAM stage groups following treatment. Using multivariate analysis, such
factors could be separated from those which were attributable to inadequate
treatment or chemotherapeutant failure. CONCLUSIONS: Multivariate analyses for
evaluation of treatment effectiveness against multiple life cycle stages of L.
salmonis yield additional information beyond that derivable from univariate
methods. This can aid in the identification of causes of apparent treatment
failure in salmon aquaculture.
PMID- 24354937
TI - Sensitivity, specificity and predictive value of the BADS to anterior executive
dysfunction.
AB - In this study we investigated the validity of the BADS subtests to adequately
discriminate anterior lesions (AL) from posterior lesions (PL). Therefore, we
compared the performances of 30 AL patients, 22 PL patients and 29 healthy
controls (HC) on the BADS subtests. Seven standard executive test variables were
also examined. Our multiple comparisons showed that the BADS Zoo Map-Part 1 was
not indicative for AL, whereas Rule Shifting, Action Programme, Key Search, Zoo
Map-total score, and BADS-total score were found to be sensitive to AL. More
importantly, the Modified Six Element Test (MSET), and the Zoo Map-Part 2 were
highly specific for AL. In both BADS subtests AL patients performed significantly
worse than either the PL or the HC groups, whereas no significant differences on
the same variables were found between PL and HC individuals. Further logistic
regression analysis revealed that the BADSMSET was the best predictor for
distinguishing AL from PL patients, correctly classifying 78.8% of the patients.
These results suggest that the BADSMSET is an accurate screening tool for the
detection of anterior pathology. Poor performance on this BADS subtest is a
significant indicator of executive dysfunctioning after anterior brain damage.
PMID- 24354938
TI - Extending the Developmental Milestones Checklist for use in a different context
in Sub-Saharan Africa.
AB - AIM: Sub-Saharan Africa bears a disproportionate amount of global diseases
related to neurodevelopmental delays in infancy, including malnutrition, malaria
and HIV. Evaluating interventions to prevent such delays requires developmental
assessment tools appropriate for Sub-Saharan Africa. This study aimed to develop
and evaluate such a tool. METHODS: The Developmental Milestones Checklist (DMC)
was developed in Kenya to provide motor, language and personal-social scores for
children aged from 3 to 24 months. We developed an extended version (DMC-II) in
Burkina Faso, West Africa, and then evaluated the reliability and sensitivity of
the scores to age and nutritional and environmental measures. RESULTS: The
internal, interinterviewer and test-retest reliability of the DMC-II scores were
>0.7. In 214 children aged 11.6-25.4 months, each score correlated with age (rs >
0.7). In 1123 children aged 16.8-19.9 months, the scores were sensitive to
stunting, wasting and underweight (effect sizes 0.31-0.87 SD). The scores also
showed expected correlations with measures of play materials in the home and
activities with caregivers (rs = 0.13-0.41). CONCLUSION: The DMC-II is easily
used by trained fieldworkers with no previous experience in developmental
assessment. It is a practical, reliable and sensitive tool for evaluating motor,
language and personal-social development in different contexts in Sub-Saharan
Africa.
PMID- 24354943
TI - New year, new look, and new goals.
PMID- 24354939
TI - Evaluation of left atrial deformation to predict left atrial stasis in patients
with non-valvular atrial fibrillation - a pilot-study.
AB - BACKGROUND: Speckle tracking-derived strain and strain rate are recently
available parameters to assess left atrial (LA) deformation. We hypothesized that
such new parameters could be of interest to evaluate the risk of LA stasis among
patients with atrial fibrillation (AF). METHODS: Single-centre study enrolling
all patients with non-valvular AF lasting longer than 48 hours for whom no
therapeutic anticoagulation was given in the preceding 3 weeks and who were
assessed through transesophageal and transthoracic echocardiogram during a 6
month time interval. LA deformation was assessed by transthoracic echocardiogram
through speckle tracking analysis, whereas LA stasis parameters were sought on
transesophageal echocardiogram. RESULTS: Among the 82 assessed patients, LA
appendage thrombi or sludge were found in 16 (19.5%). A moderate positive
correlation was found between peak positive strain rate and maximum emptying
velocity (r = 0.589; P <0.001) and peak positive strain rate and maximum filling
velocity of the LA appendage (r = 0.651; P <0.001). Peak negative strain rate was
also found to be associated with both maximum emptying velocity (r = -0.513; P
<0.001) and maximum filling velocity of the LAA (r = -0.552; P <0.001). AF
duration, peak negative strain rate and time-to-peak positive strain were
independent predictors of LAA thrombi or sludge on multivariate analysis logistic
regression. The area under the curve for the estimated probabilities using the
obtained logistic regression model was 0.89 (95%CI 0.81-0.96; P <0.001).
CONCLUSION: Our findings suggest that LA mechanical dysfunction assessed through
speckle tracking may be of interest to predict LA stasis in the setting of AF.
PMID- 24354944
TI - The effect of cognitive load on decision making with graphically displayed
uncertainty information.
AB - An experiment examined the ability of five graphical displays to communicate
uncertainty information when end users were under cognitive load (i.e.,
remembering an eight-digit number). The extent to which people could accurately
derive information from the graphs and the adequacy of decisions about optimal
behaviors based on the graphs were assessed across eight scenarios in which
probabilistic outcomes were described. Results indicated that the load
manipulation did not have an overall effect on derivation of information from the
graphs (i.e., mean and probability estimation) but did suppress the ability to
optimize behavioral choices based on the graph. Cognitive load affected people's
use of some graphical displays (basic probability distribution function) more
than others. Overall, the research suggests that interpreting basic
characteristics of uncertainty data is unharmed under conditions of limited
cognitive resources, whereas more deliberative processing is negatively affected.
PMID- 24354945
TI - Nitrate and bromate removal by autotrophic and heterotrophic denitrification
processes: batch experiments.
AB - The effects of various parameters on bromate reduction were tested using lab
scale batch reactors with sulfur based autotrophic and methanol based
heterotrophic denitrification processes. The initial bromate (BrO3-)
concentration of 100 and 500 MUg/L was completely reduced and bromide (Br-) was
produced stoichiometrically from bromate in all batch reactors. In all
experiments, nitrate was completely reduced to below detection limit. Kinetic
studies showed that the sulfur-based autotrophic nitrate reduction rate increased
with increasing initial nitrate concentration. At stoichiometrically sufficient
methanol concentration as an external carbon source, nitrate and bromate were
reduced to below US EPA drinking water limits in heterotrophic denitrification
conditions. The methanol was completely depleted at the end of the heterotrophic
operation conditions.
PMID- 24354946
TI - Antiviral and immunomodulatory effects of a novel bacterial exopolysaccharide of
shallow marine vent origin.
AB - AIMS: To evaluate a novel exopolysaccharide (EPS1) from the recently described
haloalkaliphilic, thermophilic Bacillus licheniformis strain T14, isolated from a
shallow hydrothermal vent of Panarea Island (Italy), for its antiviral and
immunomodulatory effects against herpes simplex virus type 2 (HSV-2). METHODS AND
RESULTS: EPS1-T14 hindered the HSV-2 replication in human peripheral blood
mononuclear cells (PBMC) but not in WISH cells, indicating that cell-mediated
immunity was involved in the antiviral activity. High levels of Th1-type
cytokines were detected in supernatants of EPS1-treated PBMC, while Th2-type
cytokines were not induced. CONCLUSIONS: The novel EPS1-T14 is a water-soluble,
noncytotoxic exopolymer able to stimulate the immune response and thus contribute
to the antiviral immune defence, acting as immunomodulator. SIGNIFICANCE AND
IMPACT OF THE STUDY: The exopolysaccharide produced by B. licheniformis strain
T14, stimulator of Th1 cell-mediated immunity, could be used as therapy in
immunocompromised host.
PMID- 24354947
TI - EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization,
treatment pathways, and patient-related outcomes of Fragile X Syndrome.
AB - BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on
the X chromosome, is the most common inherited form of intellectual disability
and autism spectrum disorders. Comprehensive data are lacking, however, on the
characteristics and management patients with FXS in Germany. METHODS/DESIGN:
EXPLAIN is a prospective, observational, longitudinal registry with a non
probability sampling approach. It collects data on patient characteristics,
therapeutic interventions, psychosocial parameters (including those of family
members and caregivers), quality of life of caregiver and patient, caregiver
burden, and health economic parameters, such as hospitalisation time. It is
designed to include data from 300 patients in ambulatory care from about 50
centres that employ psychiatrists, paediatricians, neurologists, and other
relevant specialists, in Germany. The study was initiated in March, 2013.
Patients will be followed for at least two years. DISCUSSION: The registry is
expected to provide much-needed data on the characteristics and management of
patients with FXS in Germany. It will also allow comparisons with other
countries, and will enable gap analyses based on current guidelines for
management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov
identifier is NCT01711606.
PMID- 24354948
TI - Percutaneous mitral repair with the MitraClip system in patients with mild-to
moderate and severe heart failure: a single-centre experience.
AB - AIMS: Edge-to-edge repair of mitral regurgitation (MR) with the MitraClip((r))
(MC) system is increasingly applied in advanced heart failure. Our objective was
to compare outcomes in patients with mild-to-moderate and severe systolic heart
failure. METHODS AND RESULTS: Between February 2010 and July 2012, 121 patients
with MR of at least grade 3+ and a mean EuroSCORE II of 10.6% underwent MC
implantation. Thirty-nine had a left ventricular ejection fraction (LVEF) of
<=30% (group A) and 82 of >30% (group B). Procedural success was comparable in
both groups (100% vs. 95.2%) with multiple (>2) clip implantation in 34% and 25%
of patients, respectively. At 12 months, absolute reduction in MR grade (2.3 vs.
2.2) and relative reduction in mitral valve orifice area (48% vs. 42%) were also
comparable. New York Heart Association class had improved independent from
baseline LVEF (P < 0.001). In-hospital mortality was low in both groups (2.6% vs.
2.4%), but there was a strong trend for higher 12-month mortality in group A (34%
vs. 18%, P = 0.05) with no significant difference in the overall rate of major
adverse cerebrovascular and cardiac events (36.8% vs. 28.9%, P = 0.38). On
multivariate analysis, MR grade after repair was the strongest predictor of
mortality (OR 2.121, 95% CI 1.095-4.109), whereas systolic impairment was no
independent predictor. CONCLUSIONS: Percutaneous mitral valve repair led to
comparable symptomatic improvement in patients with mild-to-moderately or
severely reduced LV function. LV-EF < 30% was not an independent predictor of
short-term mortality, which was mainly governed by residual MR after repair.
PMID- 24354949
TI - Barriers to the vaccination of children and adolescents and possible solutions.
AB - The benefits of vaccination are clearly demonstrated by the eradication or
enormous decline in the incidence of many vaccine-preventable diseases, but the
coverage of many highly recommended vaccines is still frequently inadequate and
children continue to suffer from diseases that could have been prevented. The
main aim of this paper is to discuss the recognized barriers to the vaccination
of children and adolescents confronting national health systems, providers and
parents, and the ways in which they can be overcome. Most of the problems
underlying limited vaccination coverage among children are due to a lack of
understanding on the part of healthcare providers and parents, which underlines
the need for educational programmes specifically addressed to each of these
groups. It is also essential that all of the physicians providing immunization
develop approaches that acknowledge parents' concerns and respectfully try to
correct any misinformation. Other means of extending vaccine coverage include the
implementation of adequate systems for recording vaccine administration and the
activation of effective reminder/recall systems, the provision of immunization
services in some medical care specialties or by integrating healthcare sites, and
the elimination or reduction of all the problems that currently limit access to
vaccination services. However, it will take the combined efforts of healthcare
systems and providers to pull down all of the barriers.
PMID- 24354950
TI - High correlation of estimated local conduction velocity with natural logarithm of
bipolar electrogram amplitude in the reentry circuit of atrial flutter.
AB - BACKGROUND: Low conduction velocity (CV) in the area showing low electrogram
amplitude (EA) is characteristic of reentry circuit of atypical atrial flutter
(AFL). The quantitative relationship between CV and EA remains unclear. We
characterized AFL reentry circuit in the right atrium (RA), focusing on the
relationship between local CV and bipolar EA on the circuit. METHODS AND RESULTS:
We investigated 26 RA AFL (10 with typical AFL; 10 atypical incisional AFL; 6
atypical nonincisional AFL) using CARTO system. By referring to isochronal and
propagation maps delineated during AFL, points activated faster on the circuit
were selected (median, 7 per circuit). At the 196 selected points obtained from
all patients, local CV measured between the adjacent points and bipolar EA were
analyzed. There was a highly significant correlation between local CV and natural
logarithm of EA (lnEA) (R(2) = 0.809, P < 0.001). Among 26 AFL, linear regression
analysis of mean CV, calculated by dividing circuit length (152.3 +/- 41.7 mm) by
tachycardia cycle length (TCL) (median 246 msec), and mean lnEA, calculated by
dividing area under curve of lnEA during one tachycardia cycle by TCL, showed y =
0.695 + 0.191x (where: y = mean CV, x = lnEA; R(2) = 0.993, P < 0.001). Local CV
estimated from EA with the use of this formula showed a highly significant linear
correlation with that measured by the map (R(2) = 0.809, P < 0.001). CONCLUSION:
The lnEA and estimated local CV show a highly positive linear correlation. CV is
possibly estimated by EA measured by CARTO mapping.
PMID- 24354951
TI - Defining and incorporating basic nursing care actions into the electronic health
record.
AB - PURPOSE: To develop a definition of basic nursing care for the hospitalized adult
patient and drive uptake of that definition through the implementation of an
electronic health record. DESIGN AND METHODS: A team of direct care nurses,
assisted by subject matter experts, analyzed nursing theory and regulatory
requirements related to basic nursing care. The resulting list of activities was
coded using the Clinical Care Classification (CCC) system and incorporated into
the electronic health record system of a 170-bed community hospital. RESULTS:
Nine basic nursing care activities were identified as a result of analyzing
nursing theory and regulatory requirements in the framework of a hypothetical
"well" patient. One additional basic nursing care activity was identified
following the pilot implementation in the electronic health record. The pilot
hospital has successfully passed a post-implementation regulatory review with no
recommendations related to the documentation of basic patient care. CONCLUSIONS:
This project demonstrated that it is possible to define the concept of basic
nursing care and to distinguish it from the interdisciplinary, problem-focused
plan of care. The use of the electronic health record can help clarify, document,
and communicate basic care elements and improve uptake among nurses. CLINICAL
RELEVANCE: This project to define basic nursing care activities and incorporate
into the electronic health record represents a first step in capturing meaningful
data elements. When fully implemented, these data could be translated into
knowledge for improving care outcomes and collaborative processes.
PMID- 24354952
TI - Intensive care survivors' experiences of ward-based care: Meleis' theory of
nursing transitions and role development among critical care outreach services.
AB - AIMS AND OBJECTIVES: To explore the psychosocial needs of patients discharged
from intensive care, the extent to which they are captured using existing theory
on transitions in care and the potential role development of critical care
outreach, follow-up and liaison services. BACKGROUND: Intensive care patients are
at an increased risk of adverse events, deterioration or death following ward
transfer. Nurse-led critical care outreach, follow-up or liaison services have
been adopted internationally to prevent these potentially avoidable sequelae. The
need to provide patients with psychosocial support during the transition to ward
based care has also been identified, but the evidence base for role development
is currently limited. DESIGN AND METHODS: Twenty participants were invited to
discuss their experiences of ward-based care as part of a broader study on
recovery following prolonged critical illness. Psychosocial distress was a
prominent feature of their accounts, prompting secondary data analysis using
Meleis et al.'s mid-range theory on experiencing transitions. RESULTS:
Participants described a sense of disconnection in relation to profound
debilitation and dependency and were often distressed by a perceived lack of
understanding, indifference or insensitivity among ward staff to their basic care
needs. Negotiating the transition between dependence and independence was
identified as a significant source of distress following ward transfer.
Participants varied in the extent to which they were able to express their needs
and negotiate recovery within professionally mediated boundaries. CONCLUSION:
These data provide new insights into the putative origins of the psychosocial
distress that patients experience following ward transfer. RELEVANCE TO CLINICAL
PRACTICE: Meleis et al.'s work has resonance in terms of explicating intensive
care patients' experiences of psychosocial distress throughout the transition to
general ward-based care, such that the future role development of critical care
outreach, follow-up and liaison services may be more theoretically informed.
PMID- 24354953
TI - Changes of triage by GPs during the course of prehospital emergency situations in
a Norwegian rural community.
AB - BACKGROUND: Priority grade assessment according to urgency level of the patients
(triage) is considered vital in emergency medicine casualties. Little is known of
the experiences of pre-hospital emergency medicine triage performed by General
Practitioners (GPs) in the community. In this study we bring such experiences
from a Norwegian island community, with special emphasis on over- and
undertriage. METHODS: In the island municipality of Austevoll, Western Norway,
where the GPs and the ambulance services both take part in all medical emergency
cases, all these cases were recorded during a 2-year period (2005-2007). We
compared the triage of the patients at the stage of the telephone reception of
the incident, and the subsequent revision of the triage at the first personal
examination of the patient. RESULTS: 236 emergency medical events were recorded,
comprising 240 patients. Of these, 42% were downgraded between the stages (i.e.
initially overtriaged), 11% were upgraded (i.e. initially undertriaged) and 47%
remained in unchanged priority group. Of the diagnostic groups, acute abdominal
cases had the highest probability of being upgraded between stages, while the
aggregated diagnostic group of syncopes, seizures, intoxications and traumas had
the highest probability of being downgraded. The principal reason for upgrading
was lack of necessary information at the stage of call. In a minority of cases
the upgrading was due to real patient deterioration between stages. CONCLUSIONS:
In pre-hospital triage of emergency patients, downgrading happens between
notification of events and actual patient examination in a substantial
proportion. Upgradings of cases are considerably fewer, but the potential serious
implications of upgrading warrants individual scrutiny of such cases.
PMID- 24354957
TI - The HLA locus contains novel foetal susceptibility alleles for congenital heart
block with significant paternal influence.
AB - OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes
on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.
SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of
individuals in the Swedish Congenital Heart Block (CHB) study population was
performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in
86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers,
71 fathers, 87 CHB index cases and 95 unaffected siblings). RESULTS: A case
control comparison between index cases and population-based out-of-study controls
(n = 1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a
chromosome-wide significance of P < 2.59 * 10(-6) (OR 2.21-3.12). In a family
based analysis of association of SNP markers as well as distinct MHC class I and
II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more
frequently transmitted to affected individuals (P < 0.03 and P < 0.05,
respectively), whilst HLA-DRB1*13 and HLA-Cw*06 variants were significantly less
often transmitted to affected children (P < 0.04 and P < 0.03). We further
observed marked association of increased paternal (but not maternal) HLA-DRB1*04
transmission to affected offspring (P < 0.02). CONCLUSIONS: HLA-DRB1*04 and HLA
Cw*05 were identified as novel foetal HLA allele variants that confer
susceptibility to CHB in response to Ro/SSA autoantibody exposure, whilst DRB1*13
and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal
contribution to foetal susceptibility to CHB for the first time.
PMID- 24354958
TI - Faecal microbiota transplantation and bacteriotherapy for recurrent Clostridium
difficile infection: a retrospective evaluation of 31 patients.
AB - BACKGROUND: Recurrent Clostridium difficile infection (CDI) is a significant
problem due to its increased incidence and severity. Failure rates for standard
antibiotic therapies are high. In our hospital, faecal microbiota transplantation
(FMT), or instillation of a culture mixture of known enteric bacteria in saline
as rectal bacteriotherapy (RBT), has long been used as 'rescue therapy' in
patients with recurrent disease, in whom repeated courses of standard antibiotic
treatment have failed. We wanted to evaluate the effectiveness of FMT and RBT for
recurrent CDI. METHODS: The records of 31 patients treated with either FMT or RBT
for recurrent CDI were reviewed retrospectively. FMT was based on faecal donation
by a close relative and RBT on a defined saline mixture of 10 individually
cultured enteric bacterial strains originally isolated from healthy persons. Both
types of instillation were carried out through a rectal catheter. FMT (500 ml)
was given as 1 installation. RBT (200 ml) was given as 2 or 3 installations with
an interval of 2 days between courses. Treatment success was defined as a
sustained loss of symptoms and discontinuation of diarrhoea within 3 days.
RESULTS: Of 31 patients, 23 (74%) responded successfully to the treatment: 16 of
23 (70%) receiving FMT and 7 of 8 (88%) receiving RBT. CONCLUSION: We found FMT
to be effective in patients with recurrent CDI. RBT based on a predefined
bacterial suspension was as effective as or better than FMT based on faecal
donation; however, multiple installations may be needed.
PMID- 24354959
TI - Tigecycline therapy for infections due to carbapenemase-producing Klebsiella
pneumoniae in critically ill patients.
AB - BACKGROUND: The aim of this study was to assess the efficacy of tigecycline in
the treatment of infections due to carbapenemase-producing Klebsiella pneumoniae
(CPKP) in critically ill patients. METHODS: A retrospective observational study
was conducted in critically ill patients receiving different tigecycline doses
for severe CPKP infections. We evaluated demographic data, localization and
severity of infection, response to therapy, and mortality. RESULTS: Fifteen
patients received tigecycline for 16 episodes of CPKP infection. The main
infections were pneumonia (31%), urinary tract infection (31%), peritonitis
(20%), catheter-related bacteraemia (12%), and meningitis (6%). Most infections
were complicated with severe sepsis (44%), septic shock (12%), and/or bacteraemia
(19%). The daily maintenance dose of tigecycline was 200 mg in 10 episodes and
100 mg in 6 episodes. The overall 30-day mortality rate was 25%. Univariate
analysis showed that mortality was significantly associated (p < 0.01) with mean
APACHE II and SOFA scores and the presence of immunosuppression, but not with the
tigecycline dose. CONCLUSIONS: Tigecycline appears to be an effective therapy for
severe infections due to CPKP in critically ill patients. Mortality is related to
the severity of the underlying disease. We observed no benefit from a higher
maintenance dose of tigecycline, although the number of patients included in the
study was too small to draw any general conclusions in this regard.
PMID- 24354961
TI - Behcet's disease associated with malignancy: a report of 41 Chinese cases.
AB - OBJECTIVE: To identify the clinical characteristics of Behcet's disease (BD)
associated with malignancies. METHOD: Among 651 BD patients sequentially
hospitalized in Peking Union Medical College Hospital from 1995 to 2012, 41
patients developed malignancies. Clinical characteristics were compared between
patients with and without malignancies, as well as between patients with
hematological and solid malignancies. RESULTS: The numbers of patients with
various types of malignancies were listed as follows: (i) 29 cases developed
hematologic malignancies which included myelodysplastic syndrome (MDS) as the
most common diagnosis in 20 cases, leukemia in seven cases, anaplastic anemia in
two cases and lymphoma in one case; (ii) 13 cases developed malignant solid
neoplasms which included colorectal cancer in three cases, urothelial carcinoma
of bladder in two cases, esophageal cancer, gastric cancer, pancreatic cancer,
thyroid cancer, breast cancer, cervical cancer, renal cell carcinoma and
metastatic adenocarcinoma of unknown primary in one case each. Female gender,
older age and gastrointestinal tract involvement were more frequently observed
among patients with malignancy than those without. Older age, longer disease
duration were more commonly seen in BD patients with solid neoplasms than in
those with hematologic malignancies. Exacerbation of BD manifestations during the
emergence of malignancy was more frequently observed among patients with
hematologic malignancies than among those with malignant solid neoplasms.
CONCLUSION: This study demonstrated that MDS and colorectal cancer were the most
common hematologic malignancy and malignant solid neoplasm associated with BD,
respectively. Gastrointestinal involvement is likely to be a risk factor for BD
patients to develop malignancy. Further studies will be required to ascertain the
pathogenic link between these two entities.
PMID- 24354962
TI - Particle characterization in retail environments: concentrations, sources, and
removal mechanisms.
AB - Particles in retail environments can have consequences for the occupational
exposures of retail workers and customers, as well as the energy costs associated
with ventilation and filtration. Little is known about particle characteristics
in retail environments. We measured indoor and outdoor mass concentrations of
PM10 and PM2.5 , number concentrations of submicron particles (0.02-1 MUm), size
resolved 0.3-10 MUm particles, as well as ventilation rates in 14 retail stores
during 24 site visits in Pennsylvania and Texas. Overall, the results were
generally suggestive of relatively clean environments when compared to
investigations of other building types and ambient/occupational regulatory
limits. PM10 and PM2.5 concentrations (mean +/- s.d.) were 20 +/- 14 and 11 +/-
10 MUg/m(3), respectively, with indoor-to-outdoor ratios of 1.0 +/- 0.7 and 0.88
+/- 1.0. Mean submicron particle concentrations were 7220 +/- 7500
particles/cm(3) with an indoor-to-outdoor ratio of 1.18 +/- 1.30. The median
contribution to PM10 and PM2.5 concentrations from indoor sources (vs. outdoors)
was 83% and 53%, respectively. There were no significant correlations between
measured ventilation rates and particle concentrations of any size. When
examining options to lower PM2.5 concentrations below regulatory limits, the
required changes to ventilation and filtration efficiency were site specific and
depended on the indoor and outdoor concentration, emission rate, and infiltration
level. PRACTICAL IMPLICATIONS: Little is known about particle concentrations,
contribution of indoor sources, and emission rates in retail environments.
Knowledge of these particle characteristics informs health scientists with input
parameters to include in exposure modeling. The predicted concentration change in
response to different ventilation rates and filtration efficiencies may be used
for guidance to develop control strategies to lower particulate matter
concentrations in retail environments.
PMID- 24354963
TI - Paxillin and carbonic anhydrase IX are prognostic markers in gallbladder squamous
cell/adenosquamous carcinomas and adenocarcinomas.
AB - AIMS: Squamous cell/adenosquamous carcinomas (SC/ASC) are rare subtypes of
gallbladder cancers (GBCs). Clinical characteristics of SC/ASC have not been well
documented, and no biological markers of GBC carcinogenesis, progression and
prognosis are available. METHODS AND RESULTS: We measured paxillin and CAIX
expression in 46 SC/ASCs and 80 adenocarcinomas (ACs) with immunohistochemistry
and correlated these data with clinicopathological characteristics. Both paxillin
expression and CAIX expression were associated significantly with larger tumours,
a higher tumour-node-metastasis (TNM) stage, lymph node metastasis and
invasiveness of SC/ASC and AC. Univariate Kaplan-Meier analysis confirmed that
paxillin and CAIX expression were associated closely with decreased overall
survival in SC/ASC (both P < 0.001) and AC (both P < 0.001). Multivariate Cox
regression analysis confirmed that paxillin expression and CAIX expression both
independently predicted poor prognosis in SC/ASC and AC patients. We also noted
correlations with survival and tumour differentiation, tumour size, TNM stage,
lymph node metastasis, tumour invasiveness and sample procurement methods.
CONCLUSIONS: Paxillin expression and CAIX expression are both related to
clinical/biological behaviour and poor prognosis of GBC.
PMID- 24354960
TI - Cap-binding complex (CBC).
AB - The 7mG (7-methylguanosine cap) formed on mRNA is fundamental to eukaryotic gene
expression. Protein complexes recruited to 7mG mediate key processing events
throughout the lifetime of the transcript. One of the most important mediators of
7mG functions is CBC (cap-binding complex). CBC has a key role in several gene
expression mechanisms, including transcription, splicing, transcript export and
translation. Gene expression can be regulated by signalling pathways which
influence CBC function. The aim of the present review is to discuss the
mechanisms by which CBC mediates and co-ordinates multiple gene expression
events.
PMID- 24354964
TI - Clinical validation of a non-heteronormative version of the Social Interaction
Anxiety Scale (SIAS).
AB - INTRODUCTION: Despite welcomed changes in societal attitudes and practices
towards sexual minorities, instances of heteronormativity can still be found
within healthcare and research. The Social Interaction Anxiety Scale (SIAS) is a
valid and reliable self-rating scale of social anxiety, which includes one item
(number 14) with an explicit heteronormative assumption about the respondent's
sexual orientation. This heteronormative phrasing may confuse, insult or alienate
sexual minority respondents. A clinically validated version of the SIAS featuring
a non-heteronormative phrasing of item 14 is thus needed. METHODS: 129
participants with diagnosed social anxiety disorder, enrolled in an Internet
based intervention trial, were randomly assigned to responding to the SIAS
featuring either the original or a novel non-heteronormative phrasing of item 14,
and then answered the other item version. Within-subject, correlation between
item versions was calculated and the two scores were statistically compared. The
two items' correlations with the other SIAS items and other psychiatric rating
scales were also statistically compared. RESULTS: Item versions were highly
correlated and scores did not differ statistically. The two items' correlations
with other measures did not differ statistically either. CONCLUSIONS: The SIAS
can be revised with a non-heteronormative formulation of item 14 with
psychometric equivalence on item and scale level. Implications for other
psychiatric instruments with heteronormative phrasings are discussed.
PMID- 24354965
TI - Specific cancer rates may differ in patients with hereditary haemorrhagic
telangiectasia compared to controls.
AB - BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is inherited as an
autosomal dominant trait, affects ~1 in 5,000, and causes multi-systemic vascular
lesions and life-limiting complications. Life expectancy is surprisingly good,
particularly for patients over 60ys. We hypothesised that individuals with HHT
may be protected against life-limiting cancers. METHODS: To compare specific
cancer rates in HHT patients and controls, we developed a questionnaire capturing
data on multiple relatives per respondent, powered to detect differences in the
four most common solid non skin cancers (breast, colorectal, lung and prostate),
each associated with significant mortality. Blinded to cancer responses, reports
of HHT-specific features allowed assignment of participants and relatives as HHT
subjects, unknowns, or controls. Logistic and quadratic regressions were used to
compare rates of specific cancer types between HHT subjects and controls.
RESULTS: 1,307 participants completed the questionnaire including 1,007 HHT
subjects and 142 controls. The rigorous HHT diagnostic algorithm meant that 158
(12%) completed datasets were not assignable either to HHT or control status. For
cancers predominantly recognised as primary cancers, the rates in the controls
generally matched age-standardised rates for the general population. HHT subjects
recruited through the survey had similar demographics to controls, although the
HHT group reported a significantly greater smoking habit. Combining data of
participants and uniquely-reported relatives resulted in an HHT-arm of 2,161 (58%
female), and control-arm of 2,817 (52% female), with median ages of 66ys [IQR 53
77] and 77ys [IQR 65-82] respectively. In both crude and age-adjusted regression,
lung cancers were significantly less frequent in the HHT arm than controls (age
adjusted odds ratio 0.48 [0.30, 0.70], p = 0.0012). Breast cancer prevalence was
higher in HHT than controls (age-adjusted OR 1.52 [1.07, 2.14], p = 0.018).
Overall, prostate and colorectal cancer rates were equivalent, but the pattern of
colorectal cancer was modified, with a higher prevalence in younger HHT patients
than controls. CONCLUSIONS: These preliminary survey data suggest clinically
significant differences in the rates of lung, breast and colorectal cancer in HHT
patients compared to controls. For rare diseases in which longitudinal studies
take decades to recruit equivalent datasets, this type of methodology provides a
good first-step method for data collection.
PMID- 24354966
TI - The role of total parenteral nutrition in inflammatory bowel disease: current
aspects.
AB - Total parenteral nutrition (TPN) represents a therapeutic modality that could
save the life of a patient with inflammatory bowel disease (IBD) facing severe
nutritional problems, by restoring the patient's impaired nutritional status. TPN
does not compete with enteral nutrition (EN), the latter being the first choice
for all patients having anatomically intact and functionally normal digestive
tract. TPN allows bowel rest while supplying adequate calorific intake and
essential nutrients, and removes antigenic mucosal stimuli. The value of TPN in
malnourished patients with intestinal failure due to CD is beyond doubt. However,
it is difficult to suggest TPN as a sole treatment for active CD. An increased
rate of remission could not be expected by applying TPN. The utility of TPN is
restricted to certain cases involving efforts to close enterocutaneous or other
complicated fistulas in patients with fistulizing CD, the treatment of short
bowel syndrome following extensive resections for CD, or when EN is impractical
for other reasons. There are no advantages of TPN therapy over EN therapy
regarding fistula healing. TPN has no influence on the surgical intervention rate
and little benefit by bypassing the intestinal passage could be expected. Also
TPN shows no advantage if the disease is chronically active. However, an optimal
supply of nutrients improves bowel motility, intestinal permeability and
nutritional status, and reduces inflammatory reactions. TPN might be associated
with an increased risk of adverse events, although TPN undertaken by experienced
teams does not cause more complications than does EN.
PMID- 24354967
TI - Trends in cholecystectomy rates in a defined population during and after the
period of transition from open to laparoscopic surgery.
AB - OBJECTIVE: To evaluate cholecystectomy rates in a Norwegian county during the
transition time from open to laparoscopic surgery, with focus on the incident
rate of laparoscopic operations, sex differences, age at operation, and
indications for cholecystectomy. MATERIAL AND METHODS: All 2615 patients living
in North Trondelag County and operated with cholecystectomy for benign biliary
disease between 1990 and 2011 were identified. Poisson regression was used to
analyze factors associated with cholecystectomy incidence rate ratios (IRRs).
RESULTS: The proportion of completed laparoscopic cholecystectomies was 8% in
1992, 50% in 1994, 94% in 2003 and 99% in 2011. The incidence of cholecystectomy
increased from 6.2 per 10 000 person-years in 1990-1992, 8.0 in 1993-1997, to
10.0 in 1998-2003 and remained at this level with a rate of 10.7 during 2004
2011. Adjusting for age at each year of surgery the IRR for females compared with
males was 2.3(2.1-2.5) p < 0.001. The median age at operation was 60.2 years (13
90) in males, 50.1 years (12-93) in females p < 0.001. The median age diminished
by 5 years in both males and females. A conversion from laparoscopic to open
surgery decreased significantly by calendar year of surgery, increased with age
of the patient, and was less often in surgery for gallstone colic than for other
indications. CONCLUSIONS: During the introduction of laparoscopic surgery, the
rates of cholecystectomy increased and remained stable at a higher level during
the later years of the study. The rate of completed laparoscopic operations
increased from 8% in 1992 to 99% in 2011.
PMID- 24354968
TI - Heroin use impairs smoking cessation among Australian prisoners.
AB - BACKGROUND: Prisoners have extremely high rates of smoking with rates 3-4 times
higher than the general community. Many prisoners have used heroin. The aims of
this study were to investigate the impact of heroin use on smoking cessation and
the social determinants of health among prisoners. METHODS: Secondary analysis of
data from a randomised controlled trial of a multi-component smoking cessation
intervention involving 425 Australian male prisoners. Inmates who, prior to
imprisonment, used heroin regularly were compared to those who did not use heroin
regularly. Self-reported smoking status was validated at baseline and each follow
up by measuring carbon monoxide levels. Readings exceeding 10 ppm were defined as
indicating current smoking. RESULTS: Over half (56.5%) of the participants had
ever used heroin while 37.7% regularly (daily or almost daily) used heroin in the
year prior to entering prison. Prisoners who regularly used heroin had
significantly worse social determinants of health and smoking behaviours,
including lower educational attainment, more frequent incarceration and earlier
initiation into smoking. Prisoners who regularly used heroin also used and
injected other drugs significantly more frequently. At 12-month follow-up, the
smoking cessation of prisoners who had regularly used heroin was also
significantly lower than prisoners who did not regularly use heroin, a finding
confirmed by logistic regression. CONCLUSIONS: Regular heroin use prior to
imprisonment is an important risk factor for unsuccessful attempts to quit
smoking among prisoners and is also associated with worse social determinants of
health, higher drug use, and worse smoking behaviours. More effective and earlier
smoking cessation interventions are required for particularly disadvantaged
groups. TRIAL REGISTRATION: This trial is registered with the Australian New
Zealand Clinical Trials Registry 12606000229572.
PMID- 24354969
TI - Economic and health consequences of COPD patients and their spouses in Denmark-
1998-2010.
AB - OBJECTIVE: Chronic Obstructive Pulmonary Disease (COPD) is among the leading
causes of morbidity and mortality worldwide, but longitudinal studies of the
economic consequences of COPD are scarce. This study evaluated the economic
consequences of COPD patients in Denmark and their spouses at a national level
before and after initial diagnosis. METHODS: Using records from the Danish
National Patient Registry (1998-2010), 171,557 patients with COPD and 86,260
spouses were identified; patients were compared with 664,821, and the spouses
with 346,524, all controls were randomly selected and matched for age, gender and
residence. Direct and indirect costs, including frequency of primary and
secondary sector contacts and procedures, medication, unemployment benefits and
social transfer payments were extracted from national databases for patients,
spouses and controls. RESULTS: COPD patients are earning approximately half of
that of controls before diagnosis. After diagnosis this effect diminishes due to
people getting older and retiring from work (65 years). Total health expenses are
more than twice as high in the COPD group regardless of age and gender compared
to controls. Spouses of COPD patients had significantly higher rates of health
related contacts, medication use and higher socioeconomic costs compared to
controls. The employment and income rates of employed spouses of COPD patients
were significantly lower compared to controls. CONCLUSION: This study provides
unique data on the economic consequences of COPD patients in Denmark and their
spouses as well as displaying the serious health consequences for the individual
spouse and society. Second, data shows substantial impact of COPD on income level
and health expenses regardless of age and gender. It could be speculated that
early identification and intervention might contribute to more health and
economic equality between patients and controls.
PMID- 24354971
TI - The future of prenatal molecular diagnostics: impact of the changing patent
landscape.
PMID- 24354970
TI - Using radiology reports to encourage evidence-based practice in the evaluation of
small, incidentally detected pulmonary nodules. A preliminary study.
AB - RATIONALE: Standard radiology report forms do not guide ordering clinicians
toward evidence-based practice. OBJECTIVES: To test an enhanced radiology report
that estimates the probability that a pulmonary nodule is malignant and provides
explicit, professional guideline recommendations. METHODS: Anonymous,
institutional review board-approved, internet-based survey of all clinicians with
privileges at the Dartmouth-Hitchcock Medical Center comparing a standard versus
an enhanced chest computed tomography report for a 65-year-old former smoker with
an incidentally detected 7-mm pulmonary nodule. MEASUREMENTS AND MAIN RESULTS: A
total of 43% (n = 447) of 1045 eligible clinicians answered patient management
questions after reading a standard and then an enhanced radiology report (which
included the probability of malignancy and Fleischner Society guideline
recommendations). With the enhanced report, more clinicians chose the correct
management strategy (72% with enhanced versus 32% with standard report [40%
difference; 95% confidence interval (CI) = 35-45%]), appropriately made fewer
referrals to pulmonary for opinions or biopsy (21 vs. 41% [-40% difference; 95%
CI = -25 to -16%]), ordered fewer positron emission tomography scans (3 versus
13%; -10% difference; 95% CI = -13 to -7%), and fewer computed tomography scans
outside the recommended time interval (2 versus 7%; -5% difference; 95% CI = -7
to -2%). Most clinicians preferred or strongly preferred the enhanced report, and
thought they had a better understanding of the nodule's significance and
management. CONCLUSIONS: An enhanced radiology report with probability estimates
for malignancy and management recommendations was associated with improved
clinicians' response to incidentally detected small pulmonary nodules in an
internet-based survey of clinicians at one academic medical center, and was
strongly preferred. The utility of this approach should be tested next in
clinical practice.
PMID- 24354972
TI - Nature, nurture and DNA sequences.
PMID- 24354973
TI - The many means to an end: training methods in pharmaceutical and medical IP law.
PMID- 24354974
TI - EU deal allows patent-term restoration for Canada.
PMID- 24354975
TI - Patent quality.
AB - Against a backdrop of a rising generics market and increasing patent expiries,
the 'quality' of patents has become an ever more significant topic of debate.
Pharmaceutical Patent Analyst has brought together a group of leading attorneys
and IP specialists to disentangle the issue of patent quality, including its
definition and importance to the field of pharmaceutical and medical science, and
what steps could be taken to improve understanding of this important yet fluid
concept. Interviews conducted by Alexandra Sklan, Commissioning Editor.
PMID- 24354978
TI - Olfactory neuroepithelium as a cellular model for the diagnosis of
neuropsychiatric diseases.
AB - The neuroepithelium has been used as an experimental model to find biological
markers for neuropsychiatric disease diagnosis. Patent information permits
understanding of the state of the art of neuroepithelium in neuropsychiatric
disease diagnosis, as well as the identification of trends in research and
development on this theme. In this article, we discuss diverse methods for
obtaining primary cultures of olfactory neurons obtained by animal dissection or
by postmortem biopsy of human cadavers. The principal owners of patents related
to olfactory neuroepithelia are universities such as John Hopkins and Bristol
Myers Squibb. The USA has the most research lines and approved patents in the
world, while Rutgers, the State University of New Jersey, provides composition
and methods related to the diagnoses and treatment of neuropsychiatric disorders.
PMID- 24354979
TI - P2X3 and P2X2/3 receptor antagonists.
AB - This review provides a concise summary of the molecular properties of the ligand
gated P2X receptors, in particular those containing the X3 subunit, as well as an
overview comprising the most important patent applications on P2X3 and P2X2/3
receptor antagonists published since 2001. This review is mainly focused on small
molecules with P2X3 and/or P2X2/3 antagonist properties. The most important
classes of the patented compounds and conditions frequently claimed as their
therapeutic targets are also discussed. Moreover, biological activity data from
the cited patents and general prediction of druglikeness of the claimed compounds
are also provided.
PMID- 24354980
TI - Small-molecule arginase inhibitors.
AB - Arginase is an enzyme that metabolizes L-arginine to L-ornithine and urea. In
addition to its fundamental role in the hepatic ornithine cycle, it also
influences the immune systems in humans and mice. Arginase participates in many
inflammatory disorders by decreasing the synthesis of nitric oxide and inducing
fibrosis and tissue regeneration. L-arginine deficiency, which is modulated by
myeloid cell arginase, suppresses T-cell immune response. This mechanism plays a
fundamental role in inflammation-associated immunosuppression. Pathogens can
synthesize their own arginase to elude immune reaction. Small-molecule arginase
inhibitors are currently described as promising therapeutics for the treatment of
several diseases, including allergic asthma, inflammatory bowel disease,
ulcerative colitis, cardiovascular diseases (atherosclerosis and hypertension),
diseases associated with pathogens (e.g., Helicobacter pylori, Trypanosoma cruzi,
Leishmania, Mycobacterium tuberculosis and Salmonella), cancer and induced or
spontaneous immune disorders. This article summarizes recent patents in the area
of arginase inhibitors and discusses their properties.
PMID- 24354981
TI - New antibacterial agents: patent applications published in 2011.
AB - This article reviews 101 patent applications published in 2011 that disclosed
small-molecule antibacterials and reported bacterial growth inhibition, in which
the compounds were not similarly disclosed to be toxic to fungal or mammalian
cells. The patent applications were analyzed according to their biological target
and/or antibacterial class. Protein synthesis inhibitors included ligands of the
50S ribosome subunit (oxazolidinones, macrolides/ketolides and pleuromutilins),
the 30S ribosome subunit (aminoglycosides and tetracyclines) and nonribosomal
targets. DNA synthesis inhibitors included ligands of topoisomerase type II and
type IV. Inhibitors directed at the bacterial cell envelope included those that
act on cell envelope synthesis (LpxC inhibitors, penicillin-binding protein
inhibitors and glycopeptides) as well as membrane disruptors (lantibiotics).
Other antibacterial targets included cell division (FtsZ and WalR) and fatty acid
biosynthesis (FabH/I). Compounds for which the targets are unknown or undisclosed
are also covered, as are compounds aimed at overcoming resistance mechanisms
(efflux inhibitors, beta-lactamase inhibitors).
PMID- 24354984
TI - Regulation of alpha-endosulfine, an inhibitor of protein phosphatase 2A, by
multisite phosphorylation.
AB - Progression into M phase requires inhibition of heterotrimeric PP2A containing
the regulatory B55 subunit (PP2A-B55) as well as the activation of cyclin
dependent kinase 1 (Cdk1). alpha-endosulfine (ENSA)/cyclic AMP-regulated 19 kDa
phosphoprotein (ARPP-19) family proteins phosphorylated at S67 by Greatwall
kinase bind and inhibit PP2A-B55. This study shows that endogenous kinases
phosphorylate not only S67 but also two additional sites in ENSA (T28 and S109)
with different kinetics at different cell-cycle stages in Xenopus laevis intact
cells and cell-free egg extracts. When assayed in vitro, these phosphorylations
had qualitatively and/or quantitatively different effects on inhibition of PP2A
B55 by ENSA. Structural analyses revealed that the most-conserved middle region
of ENSA containing S67 physically interacts with PP2A-B55 at the interface of the
B55 and C subunits, where the catalytic centre of PP2A is located. As non
phosphorylated ENSA has an intrinsic potential for PP2A-B55 inhibition, these
three phosphorylations differentially affect physical interaction of the middle
region of ENSA with PP2A-B55. These results suggest that the two additional
phosphorylation sites together with S67 allow ENSA to function as a 'stepwise
tuner' for PP2A-B55, which may be regulated by multiple cellular signals, rather
than a simple 'on/off' switch.
PMID- 24354985
TI - Left ventricular endocardial dysfunction in patients with preserved ejection
fraction after receiving anthracycline.
AB - BACKGROUND: Anthracycline chemotherapy generates progressive dose-dependent left
ventricular (LV) dysfunction associated with a poor prognosis. Early detection of
minor LV myocardial dysfunction caused by the cardiotoxicity of anthracycline is
thus important for predicting global LV dysfunction. METHODS: Fifty patients with
preserved ejection fraction (all >=55%) after receiving anthracycline
chemotherapy were recruited for this study. Two-dimensional speckle tracking was
used to assess global radial and circumferential strains from mid-LV short-axis
views and global longitudinal strain from the apical four- and two-chamber view
as peak global strain curves. Three-dimensional (3D) radial, circumferential, and
longitudinal myocardial function was quantified as a peak global strain curve
using 3D speckle tracking from all 16 LV segments. 3D speckle tracking imaging
was used to evaluate LV endocardial area change ratio (area strain) quantified as
peak global area strain curve (3D-GAS) to determine LV endocardial function.
Twenty age-, gender-, and EF-matched normal volunteers were studied for
comparisons. RESULTS: Only 3D-GAS and peak 3D global circumferential strains of
the anthracycline group were significantly worse than those of the control group
(-43.3 +/- 3.1 vs. -45.8 +/- 4.3% and -31.6 +/- 3.5% vs. -34.4 +/- 4.2%,
respectively; P = 0.008, P = 0.004) even though global LV systolic and diastolic
functions were similar. 3D-GAS correlated significantly with the cumulative
doxorubicin dose (r = 0.316, P = 0.026). It was noteworthy that multivariate
analysis showed only 3D-GAS (beta = 0.323, P = 0.025) was independently
associated with cumulative doxorubicin dose. CONCLUSIONS: Three-dimensional
speckle tracking area strain was found useful for early detection of minor LV
endocardial dysfunction associated with the use of anthracycline, and may thus
prove to be clinically useful for predicting global LV dysfunction.
PMID- 24354986
TI - Deficient spontaneous in vitro apoptosis and increased tmTNF reverse signaling
induced apoptosis of monocytes predict suboptimal therapeutic response of
rheumatoid arthritis to TNF inhibition.
AB - INTRODUCTION: In vitro apoptosis of peripheral monocytes in rheumatoid arthritis
(RA) is disturbed and influenced by cytokine production and transmembrane TNF
(tmTNF) reverse signaling. The goal of the study was the analysis of the
predictive value of the rate of in vitro apoptosis for the therapeutic response
to anti-TNF treatment. METHODS: Spontaneous and tmTNF reverse signaling-induced
apoptosis were determined in vitro in monocytes from 20 RA patients prior to
initiation of therapeutic TNF inhibition with etanercept, and the subsequent
clinical response was monitored. RESULTS: Spontaneous in vitro apoptosis was
significantly reduced in RA patients compared to controls. Deficiency in
spontaneous apoptosis was associated with an insufficient therapeutic response
according to the European League Against Rheumatism (EULAR) response criteria and
less reduction of the disease activity determined by disease activity score (DAS)
28. High susceptibility to reverse signaling-induced apoptosis was also
associated with less efficient reduction in the DAS28. Of note, a strong negative
correlation between the two apoptotic parameters was discernible, possibly
indicative of two pathogenetically relevant processes counter-regulating each
other. tmTNF reverse signaling induced in vitro production of soluble IL1-RI and
IL-1RII only in monocytes not deficient in spontaneous apoptosis, and the levels
of soluble IL1-RII were found to be predictive of a good clinical response to
Etanercept. CONCLUSION: Although tmTNF reverse signaling is able to induce
apoptosis of RA monocytes in vitro, this process appears to occur in vitro
preferentially in patients with suboptimal therapeutic response. Resistance to
spontaneous in vitro apoptosis, in contrast, is a predictor of insufficient
response to treatment.
PMID- 24354987
TI - Dentistry for Jordanians with special needs.
AB - There are thousands of residents with disabilities in Jordan. Despite national
legislation to assure individuals with disabilities needed services, including
education and employment, social inclusion of these individuals is difficult
since societal views exclude them from functioning as members of a community.
While there are no national studies of the dental needs of individuals with
disabilities in Jordan, local reports indicates limited use of dental services
and the need for increased oral hygiene and restorative services. Examples of
dental education accreditation standards in other countries are used as models
for the improvement in the preparation of dental students to provide services for
individuals with special needs.
PMID- 24354988
TI - Education and Imaging. Gastrointestinal: sessile serrated adenoma/polyps with a
minute T1 colorectal carcinoma.
PMID- 24354989
TI - Education and Imaging. Gastrointestinal: challenging case of Whipple's disease
with remarkable abdominal lymphadenopathy.
PMID- 24354990
TI - Education and Imaging. Gastrointestinal: painful anal mass in a young patient
with rectal bleeding.
PMID- 24354991
TI - Education and Imaging. Hepatobiliary and pancreatic: choledochal cyst with
involvement of the cystic duct.
PMID- 24354992
TI - Education and Imaging. Hepatobiliary and pancreatic: peliosis hepatis associated
with multiple myeloma.
PMID- 24354993
TI - Use of capsule endoscopy in patients with Crohn's disease in Japan: a multicenter
survey.
AB - BACKGROUND AND AIM: Until the approval of patency capsule, capsule endoscopy (CE)
has not been routinely applied for the diagnosis of Crohn's disease (CD) in
Japan. We aimed to survey current situation of CE use for patients with CD in
Japan. METHODS: The nationwide survey of 40 Japanese institutions identified 94
patients with established CD (eCD) and 80 patients with suspected CD (sCD), who
were examined by CE. Types and positive rates of mucosal injury under CE and
capsule retention rate were investigated. In sCD, final diagnosis after CE was
also analyzed. RESULTS: Patients with eCD comprised 82 patients of ileitis or
ileocolitis type, while 12 patients had CD of colitis type. CE identified mucosal
injuries in 83 of 94 patients. Eight of 12 patients with eCD of colitis type had
ileal lesions under CE, thereby being reclassified as ileocolitis type. In
patients with sCD, CE detected mucosal injuries in 58 patients. Linear ulceration
and cobblestone appearance were depicted in 22 and 3 patients, respectively,
thereby resulting in established diagnosis of CD in 23 patients. Mucosal lesion
was not found in 22 patients with sCD, who were diagnosed as not having CD.
Capsule retention rate was not statistically different between patients with eCD
and those with sCD (7.4% vs 6.3%, P = 1.0). CONCLUSIONS: CE is useful for the
evaluation of small bowel mucosal injuries in Japanese patients with sCD and eCD.
Possible intestinal stricture needs to be carefully evaluated before CE even in
patients with sCD.
PMID- 24354994
TI - Evaluation of alpha-fetoprotein in detecting hepatocellular carcinoma recurrence
after radiofrequency ablation.
AB - BACKGROUND AND AIM: The performance of alpha-fetoprotein (AFP) in the detection
of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation was
analyzed. METHODS: One hundred and forty-six solitary HCC lesions treated by
radiofrequency ablation were evaluated. Using the AFP cutoff level at >= 20
ng/mL, tumors were categorized into AFP or non-AFP-producing HCC. Factors
associated with true and false interpretations for cancer recurrence including
analysis of elevated alanine aminotransferase (ALT) were evaluated. The
performance of AFP using different cutoff levels adjusted for abnormal ALT was
compared. RESULTS: Of 146 HCCs, 103 demonstrated no HCC recurrence while 43 had
local recurrence. In non-recurrence HCC cases, increased AFP levels (false
positive) were associated with concomitant ALT elevations, while those with
normal AFP (true negative) had correspondingly normal ALT values (P < 0.001). The
AFP false positive rate in cases of elevated ALT was significantly higher than
those with normal ALT levels (31.9% vs 5.4%, P = 0.001). Among all positive AFP
tests, those with false positive values (non-recurrence) had a significantly
lower AFP level than the true positive (recurrence) HCC cases (39.8 ng/mL vs 372
ng/mL, P < 0.001). At the 20 ng/mL cutoff level, the sensitivities of AFP for
detecting recurrence in non-AFP-producing HCC and AFP-producing HCC were 12.0%,
and 72.2%, respectively. Using a modified AFP criteria of >= 100 ng/mL for cases
where ALT >= 40 U/L, the sensitivity and specificity in AFP-producing tumors
increased from 72.2% and 56% to 100% and 85%, respectively. CONCLUSION: Serum AFP
is a useful test in the detection of HCC recurrence in AFP-producing HCC. The
performance in AFP-producing HCC was significantly improved after adjusting for
elevation of serum ALT.
PMID- 24354995
TI - Higher adherence with 3-year entecavir treatment than lamivudine or telbivudine
in treatment-naive Taiwanese patients with chronic hepatitis B.
AB - BACKGROUND AND AIMS: Oral nucleos(t)ide analogs (NAs) are effective in
suppressing hepatitis B virus (HBV) replication in treatment naive chronic
hepatitis B (CHB) patients. However, little is known about the treatment
modification and adherence on such patients with prolonged NA treatment. METHODS:
In this multicenter observational study, a total of 600 NA-naive Taiwanese CHB
patients aged 16 years and older were enrolled. The 600 patients were
retrospectively identified by their NA treatment history from August 2008 to July
2009; this cohort was prospectively followed up over 3 years. During the 3-year
period, incidence of treatment modifications, reasons for modification, and rate
of adherence were evaluated. RESULTS: Among the 583 evaluable patients, the
initial NA treatment included entecavir (ETV) in 468 patients, telbivudine (LdT)
in 67, and lamivudine (LVD) in 48. During the 3-year treatment, 9.0% of ETV
treated patients, 38.8% of LdT-treated patients, and 54.2% of LVD-treated
patients had treatment modification. The main reasons for treatment modification
were fulfilling stopping criteria in the ETV group (40.5%) and virological
breakthrough in both the LdT (61.5%) and LVD (46.2%) groups. The proportion of
patients with adherence rate (> 90%) at year 3 was 90.8% in the ETV group, 83.9%
in the LdT group, and 83.9% in the LVD group. CONCLUSIONS: Treatment-naive CHB
patients with a 3-year ETV treatment in Taiwan have the lower likelihood of
treatment modification and better rate of adherence compared with those with LdT
or LVD treatment.
PMID- 24354996
TI - Systematic review or meta-analysis? Their place in the evidence hierarchy.
PMID- 24354997
TI - A patient-focused framework integrating self-management and informatics.
AB - PURPOSE: This article introduces a framework to (a) guide chronic illness self
management interventions through the integration of self-management and nursing
informatics, (b) focus self-management research, and (c) promote ethical, patient
empowering technology use by practicing nurses. METHODS: Existing theory and
research focusing on chronic illness, self-management, health-enabling
technology, and nursing informatics were reviewed and examined and key concepts
were identified. A care paradigm focusing on concordance, rather than compliance,
served as the overall guiding principle. FINDINGS: This framework identifies key
relationships among self-management (patient behaviors), health force (patient
characteristics), and patient-defined goals. The role of health-enabling
technology supporting these relationships is explored in the context of nursing
informatics. CONCLUSIONS: The Empowerment Informatics framework can guide
intervention design and evaluation and support practicing nurses' ethical use of
technology as part of self-management support. CLINICAL RELEVANCE: Nurses
worldwide provide support to patients who are living with chronic illnesses. As
pressures related to cost and access to care increase, technology-enabled self
management interventions will become increasingly common. This patient-focused
framework can guide nursing practice using technology that prioritizes patient
needs.
PMID- 24354998
TI - Quality of life before and after cosmetic surgery.
AB - This article reviews the literature regarding the impact of cosmetic surgery on
health-related quality of life (QOL). Studies were identified through
PubMed/Medline and PsycINFO searches from January 1960 to December 2011. Twenty
eight studies were included in this review, according to specific selection
criteria. The procedures and tools employed in cosmetic surgery research studies
were remarkably diverse, thus yielding difficulties with data analysis. However,
data indicate that individuals undergoing cosmetic surgery began with lower
values on aspects of QOL than control subjects, and experienced significant QOL
improvement post-procedurally, an effect that appeared to plateau with time.
Despite the complexity of measuring QOL in cosmetic surgery patients, most
studies showed an improvement in QOL after cosmetic surgery procedures. However,
this finding was clouded by measurement precision as well as heterogeneity of
procedures and study populations. Future research needs to focus on refining
measurement techniques, including developing cosmetic surgery-specific QOL
measures.
PMID- 24354999
TI - Interaction of Al(2)O(3) nanoparticles with Escherichia coli and their cell
envelope biomolecules.
AB - AIMS: The aim of this study is to investigate the antibacterial activity of
aluminium oxide nanoparticles (Al2 O3 NPs) against multidrug-resistant clinical
isolates of Escherichia coli and their interaction with cell envelope
biomolecules. METHODS AND RESULTS: Al2 O3 NPs were characterized by scanning
electron microscope (SEM), high-resolution transmission electron microscope (HR
TEM) and X-ray diffraction (XRD) analyses. Antibacterial activity and interaction
of Al2 O3 NPs with E. coli and its surface biomolecules were assessed by
spectrophotometry, SEM, HR-TEM and attenuated total reflectance/Fourier transform
infrared (ATR-FTIR). Of the 80 isolates tested, about 64 (80%) were found to be
extended spectrum beta-lactamase (ESBL) positive and 16 (20%) were non-ESBL
producers. Al2 O3 NPs at 1000 MUg ml(-1) significantly inhibited the bacterial
growth. SEM and HR-TEM analyses revealed the attachment of NPs to the surface of
cell membrane and also their presence inside the cells due to formation of
irregular-shaped pits and perforation on the surfaces of bacterial cells. The
intracellular Al2 O3 NPs might have interacted with cellular biomolecules and
caused adverse effects eventually triggering the cell death. ATR-FTIR studies
suggested the interaction of lipopolysaccharide (LPS) and L-alpha-Phosphatidyl
ethanolamine (PE) with Al2 O3 NPs. Infrared (IR) spectral changes revealed that
the LPS could bind to Al2 O3 NPs through hydrogen binding and ligand exchange.
The Al2 O3 NPs-induced structural changes in phospholipids may lead to the loss
of amphiphilic properties, destruction of the membrane and cell leaking.
CONCLUSIONS: The penetration and accumulation of NPs inside the bacterial cell
cause pit formation, perforation and disorganization and thus drastically disturb
its proper function. The cell surface biomolecular changes revealed by ATR-FTIR
spectra provide a better understanding of the cytotoxicity of Al2 O3 NPs.
SIGNIFICANCE AND IMPACT OF THE STUDY: Al2 O3 NPs may serve as broad-spectrum
bactericidal agents to control the emergent pathogens regardless of their drug
resistance mechanisms.
PMID- 24355000
TI - Changes in decisional conflict and decisional regret in patients with localised
prostate cancer.
AB - AIMS AND OBJECTIVES: To identify the changes and associated factors in decisional
conflict and regret in patients with localised prostate cancer up to six months
postprimary treatment. BACKGROUND: Various treatments of differing qualities can
be used for patients with localised prostate cancer; these treatments may cause
conflicts in treatment decision-making and post-treatment regret. DESIGN: A
quantitative longitudinal study. METHODS: A total of 48 patients were recruited
from a 3700-bed medical centre in northern Taiwan and assessed at pretreatment
and one and six months post-treatment. Demographic characteristics, clinical
information and results from the psychosocial adjustment to illness scale,
decisional conflict scale and decision regret scale were collected. Data were
analysed based on the generalised estimating equations models. RESULTS: The
overall decisional conflict substantially improved over time. However, the
feeling of being less informed was high and did not improve considerably during
the study period. Education level, decision preferences and psychosocial
adjustment were associated with decisional conflict and influenced decision
making. The feeling of ineffective decision-making and decisional regret was low,
post-treatment. Psychosocial adjustment was associated with effective decision
making and decisional regret. CONCLUSION: In patients with localised prostate
cancer, decisional conflict reduced considerably up to six months post-treatment.
Moreover, the patients were satisfied with their treatment decision-making and
believed that they had made the correct choice up to six months post-treatment.
However, patients may have experienced feelings of being less informed pre- and
post-treatment, particularly those with lower education levels, a preference for
passive roles, or inferior psychosocial adjustment. Consequently, health
professionals must provide adequate medical information and psychosocial
intervention to help patients in the decision-making process. RELEVANCE TO
CLINICAL PRACTICE: Nurses and healthcare providers must provide localised
prostate cancer patients with adequate information and psychosocial intervention
to reduce decisional conflict.
PMID- 24355001
TI - Comparative analysis of curative effect of CT-guided stem cell transplantation
and open surgical transplantation for sequelae of spinal cord injury.
AB - BACKGROUND: This study compared the clinical efficacies, advantages and
disadvantages of two transplantation approaches for treating spinal cord injury:
open surgical exploration combined with local stem cell transplantation (referred
to as open surgical transplantation) and local stem cell transplantation by CT
guided puncture (referred to as CT-guided transplantation). METHODS: The patients
were divided into the following three groups to perform a retrospective
controlled study: Group A included nine patients who underwent open surgical
transplantation, Group B included nine patients who underwent CT-guided
transplantation, and Group C included nine patients who did not receive stem cell
transplantation. The Abbreviated Injury Scale (AIS), the American Spinal Injury
Association (ASIA) score and the motor evoked potentials (MEP) examination were
utilized to compare the differences in the clinical efficacies. The advantages
and disadvantages of the two transplantation approaches were also compared,
including the surgical risks, the possibility of repeating the operation, the
interval between surgery and rehabilitation exercises and the scope of conditions
suitable for the operation. RESULTS: Whether evaluated by the AIS grading scale,
the ASIA score or the MEP results, there were significant differences in the
clinical efficacy among the three patient groups. Group B exhibited the best
clinical outcome, followed by Group A, and Group C fared the worst. The CT-guided
transplantation had the advantages of lower surgical risk, the potential to
repeat the operations within a short time-frame and a short interval between
surgery and rehabilitation exercise compared with the open surgical
transplantation. The conditions that are suitable for CT-guided transplantation
versus the conditions suitable for open surgical transplantation are not
identical. The application scopes for the two approaches had their respective
strengths. CONCLUSIONS: CT-guided stem cell transplantation was confirmed as a
safe and effective approach to treat sequelae of spinal cord injury with the
advantages of simpler operation, minimal invasion, less adverse reaction and
quicker recovery. TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION NUMBER:
ChiCTR-TNRC-12002477.
PMID- 24355002
TI - Experiments by nature: lessons on type 1 diabetes.
AB - The etiology and pathogenesis of type 1 diabetes (T1D) - one of the most frequent
chronic, life-debilitating diseases in humans - have long fascinated
endocrinologists, pathologists and biologists alike. Currently conventional
wisdom portrays T1D as a chronic T cell-mediated autoimmune disease that leads to
the specific destruction of pancreatic insulin-producing beta cells. The process
of beta cell destruction is accompanied (or preceded) by the production of
autoantibodies (autoAb) to beta cell antigens (i.e. insulin, GAD65, IA-2 and
ZnT8). These autoAb have proved to be instrumental in identifying subjects at
risk of developing the disease prior to overt hyperglycemia, and they help to
distinguish T1D from T2D patients (who have no autoAb), but are not deemed to be
pathogenic. This review will examine to which extent this well-established
disease-dogmas are sustained by experiments by nature, which should not suffer
from the common biases and errors of experiments by humans.
PMID- 24355003
TI - HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by
long range PCR and high-throughput sequencing.
AB - Super high-resolution single molecule sequence-based typing (SS-SBT) is a human
leukocyte antigen (HLA) DNA typing method to the field 4 level of allelic
resolution (formerly known as eight-digit typing) to efficiently detect new and
null alleles without phase ambiguity by combination of long ranged polymerase
chain reaction (PCR) amplification and next-generation sequencing (NGS)
technologies. We previously reported the development and application of the SS
SBT method for the eight classical HLA loci, A, B, C, DRB1, DQA1, DQB1, DPA1 and
DPB1. In this article, we describe the development of the SS-SBT method for three
DRB1 linked loci, DRB3, DRB4 and DRB5 (DRB3/4/5) and characterization of DRB1
DRB3/4/5 haplotype structures to the field 4 level. Locus specific PCR primers
for DRB3/4/5 were designed to amplify the gene regions from intron 1 to exon 6
[3' untranslated region (3'UTR)]. In total 20 DRB1 and 13 DRB3/4/5 allele
sequences were determined by the SS-SBT to the field 4 level without phase
ambiguity using 19 DR51, DR52 and DR53 positive genomic DNA samples obtained from
Japanese. Moreover, 18 DRB1-DRB3/4/5 haplotypes were estimated to the field 4
level by the SS-SBT method in contrast to 10 haplotypes estimated by conventional
methods to the field 1 level (formerly known as two digit typing). Therefore,
DRB1-DRB3/4/5 haplotyping by SS-SBT is expected to provide informative data for
improved HLA matching in medical research, transplantation procedures, HLA
related disease studies and human population diversity studies.
PMID- 24355004
TI - HLA phenotypes of candidates for HSCT: comparing transplanted versus non
transplanted candidates, resulting in the predictive estimation of the
probability to find a 10/10 HLA matched donor.
AB - In order to study the impact of human leucocyte antigen (HLA) polymorphism
distribution in identifying a matched haematopoietic stem cells unrelated donor
(UD), we performed a multi-centric retrospective analysis with the aim of
comparing the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 phenotypes of 2126
patients (772 patients for whom a donor search failed to identify a matched UD,
and 1354 patients who received a 10/10 allele level matched UD). Our results
showed that rare HLA-C is often responsible for difficulty in identifying a
donor. This locus may add a degree of complexity to a supposed 'frequent' HLA-A
HLA-B and HLA-DRB1 phenotype, turning this phenotype into a less frequent one.
For example, 32.5% of the phenotypes in the non-transplanted patients could not
be explained by any of the pairs of known HLA-A, HLA-B, HLA-C and HLA-DRB1
haplotypes while this percentage dropped to less than 2% if combinations of only
HLA-A, HLA-B and HLA-DRB1 haplotypes were considered. Such situations can be
anticipated by computing an index, based on HLA haplotype frequency, the average
registry sample size (ARS). ARS is defined as the inverse of the phenotype
frequency computed using all corresponding pairs of haplotype frequencies. ARS
confirmed that the most significant difference between transplanted and non
transplanted patients was correlated with the introduction of the locus HLA-C in
the analysis (median: 8.3e + 4 vs 3.1e + 6, P < 0.0001). The higher the ARS the
lower the likelihood of finding a 10/10 match UD reflecting the rareness of the
patient's HLA. The area under receiver operator characteristics (AUROC) values of
the ARS computation for HLA-A, HLA-B and HLA-DRB1 was 0.82 (0.80; 0.84) at a low
resolution level (two digits). Overall, our study promotes the use of haplotype
frequency-based computations to develop computer-assisted donor search.
PMID- 24355005
TI - HLA frequencies and associations in cystic fibrosis.
AB - Cystic fibrosis (CF) is classically attributed to the dysfunction of the single
CF transmembrane conductance regulator gene. The incidence of human leukocyte
antigen (HLA) polymorphisms in different CF-associated diseases raises the
question of an unequal distribution of HLA genotypes in CF. This study aimed to
evaluate HLA gene frequencies and possible associations in CF patients compared
with a control population. Frequencies of HLA-DRB1, HLA-DQA1 and HLA-DQB1,
performed by intermediate resolution typing using Luminex sequence-specific
oligonucleotide, and epitope counts were similar in 340 CF patients when compared
with 400 control subjects. In conclusion, HLA-DRB1, -DQA1 and -DQB1 do not seem
to influence susceptibility to CF. Whether HLA plays a role in the severity of CF
disease needs to be investigated.
PMID- 24355006
TI - Next-generation sequencing can reveal in vitro-generated PCR crossover products:
some artifactual sequences correspond to HLA alleles in the IMGT/HLA database.
AB - The high-resolution human leukocyte antigen (HLA) genotyping assay that we
developed using 454 sequencing and Conexio software uses generic polymerase chain
reaction (PCR) primers for DRB exon 2. Occasionally, we observed low abundance
DRB amplicon sequences that resulted from in vitro PCR 'crossing over' between
DRB1 and DRB3/4/5. These hybrid sequences, revealed by the clonal sequencing
property of the 454 system, were generally observed at a read depth of 5%-10% of
the true alleles. They usually contained at least one mismatch with the IMGT/HLA
database, and consequently, were easily recognizable and did not cause a problem
for HLA genotyping. Sometimes, however, these artifactual sequences matched a
rare allele and the automatic genotype assignment was incorrect. These
observations raised two issues: (1) could PCR conditions be modified to reduce
such artifacts? and (2) could some of the rare alleles listed in the IMGT/HLA
database be artifacts rather than true alleles? Because PCR crossing over occurs
during late cycles of PCR, we compared DRB genotypes resulting from 28 and (our
standard) 35 cycles of PCR. For all 21 cell line DNAs amplified for 35 cycles,
crossover products were detected. In 33% of the cases, these hybrid sequences
corresponded to named alleles. With amplification for only 28 cycles, these
artifactual sequences were not detectable. To investigate whether some rare
alleles in the IMGT/HLA database might be due to PCR artifacts, we analyzed four
samples obtained from the investigators who submitted the sequences. In three
cases, the sequences were generated from true alleles. In one case, our 454
sequencing revealed an error in the previously submitted sequence.
PMID- 24355007
TI - Genetic polymorphism in IFNL4 and response to pegylated interferon-alpha and
ribavirin in Japanese chronic hepatitis C patients.
AB - A genetic polymorphism of the newly discovered interferon-lambda 4 (IFNL4) gene
was associated with hepatitis C virus (HCV) clearance in individuals of African
ancestry. To assess whether a dinucleotide variant of IFNL4 (ss469415590) also
affected treatment outcome of antiviral therapy in Japan, we genotyped 213
patients with chronic genotype 1 HCV infection and 176 healthy subjects. The
DeltaG allele was associated with treatment failure [odds ratio (OR) 4.73, P =
0.019], as was the IFL3 rs8099917 single nucleotide polymorphism (SNP) (OR 5.06,
P = 0.068). The correlation between ss469415590 and rs8099917 was high (r(2) =
0.92, D' = 0.98). Multivariate analysis revealed that the rs8099917 SNP was
independently associated with treatment failure (OR 5.28, P = 0.009). Therefore,
ss469415590 may be another predictive marker of antiviral therapy outcome in the
Japanese population.
PMID- 24355008
TI - Group-specific amplification of HLA-DQA1 revealed a number of genomic full-length
sequences including the novel HLA alleles DQA1*01:10 and DQA1*01:11.
AB - In this article, we describe a subgroup-specific amplification assay for HLA-DQA1
that encompasses the whole coding region and allows us to sequence full-length
HLA-DQA1 genes. We introduce the novel alleles HLA-DQA1*01:10 and HLA-DQA1*01:11.
Moreover, we were able to confirm the full-length genomic sequence data of the
alleles HLA-DQA1*01:07, HLA-DQA1*03:01:01, HLA-DQA1*03:02, HLA-DQA1*04:01:02, HLA
DQA1*04:02, HLA-DQA1*05:03, HLA-DQA1*05:05:01:02 and HLA-DQA1*06:01:01. A
complete genomic overview of all six HLA-DQA1 allele groups is now available from
the submission of our data to the IMGT/HLA database. Because our approach
facilitates the analysis of all HLA-DQA1 allele sequences, HLA-DQA1 may become
the first HLA locus from which all subgroup members will be known in detail in
the near future.
PMID- 24355009
TI - Description and molecular modeling of four novel HLA-B alleles identified in
Brazilian individuals.
AB - Four novel HLA-B alleles, B*42:20, B*51:151, B*57:64 and B*58:42 were identified
in Brazilian individuals.
PMID- 24355010
TI - Detection of a novel HLA-B allele, HLA-B*08:111, in an Italian bone marrow donor.
AB - The newly detected HLA-B*08:111 allele shows two nucleotide differences from
B*08:01:01 in codons 113 and 114.
PMID- 24355011
TI - A new HLA-C allele, C*06:99, identified by sequence-based typing in a Korean
individual.
AB - The C*06:99 allele substitutes one nucleotide of C*06:02:01:01 at codon 50 (CCG
>CTG), Pro to Leu.
PMID- 24355012
TI - Identification of a novel HLA-C*08 allele, HLA-C*08:78, by sequence-based typing
in a Korean individual.
AB - HLA-C*08:78 differs from C*08:01:01 by a nonsynonymous mutation at codon 239 (GGA
to AGA) in exon 4.
PMID- 24355013
TI - Kinetic and isotherm studies of adsorption and biosorption processes in the
removal of phenolic compounds from aqueous solutions: comparative study.
AB - The phenolic compounds are known by their carcinogenicity and high toxicity as
well as creating unpleasant taste and odor in water resources. The present study
develops a cost-effective technology for the treatment of water contaminated with
phenolic compounds, including Phenol (Ph), 2-chlorophenol (2-CP), and 4
chlorophenol (4-CP). So, two sorbents, rice bran ash (RBA) and biomass of brown
algae, Cystoseiraindica, were used and results were compared with the
commercially granular activated carbon (GAC). The phenolic compounds were
determined using a high performance liquid chromatography (HPLC) under batch
equilibrium conditions. The effects of contact time, pH, initial adsorbate
concentration, and adsorbent dosages on the removal efficiency were studied. The
adsorption data were simulated by isotherm and kinetic models. Results indicated
that RBA and GAC had the lowest efficiency for the removal of 2-CP, while the
order of removal efficiency for C. indica biomass was as follows: 2-CP > 4-CP >
phenol. The efficiency of GAC was higher than those of other adsorbents for all
of the phenolic compounds. Furthermore, the adsorption capacity of RBA was found
to be higher than that of C. indica biomass. The optimal initial pH for the
removal of phenol, 2-CP and 4-CP was determined to be 5, 7, and 7 for RBA, GAC,
and algal biomass, respectively. Kinetic studies suggested that the pseudo-second
order best fitted the kinetic data.
PMID- 24355015
TI - Inhaled allergen challenge in assessment of biologics for asthma.
PMID- 24355016
TI - As strong as an OX or as weak as a kitten?
PMID- 24355017
TI - Rhinoviral infection and asthma: the detection and management of rhinoviruses by
airway epithelial cells.
AB - Human rhinoviruses (HRV) have been linked to the development of childhood asthma
and recurrent acute asthma exacerbations throughout life, and contribute
considerably to the healthcare and economic burden of this disease. However, the
ability of HRV infections to trigger exacerbations, and the link between allergic
status and HRV responsiveness, remains incompletely understood. Whilst the
receptors on human airway cells that detect and are utilized by most HRV group A
and B, but not C serotypes are known, how endosomal pattern recognition receptors
(PRRs) detect HRV replication products that are generated within the cytoplasm
remains somewhat of an enigma. In this article, we explore a role for autophagy,
a cellular homeostatic process that allows the cell to encapsulate its own
cytosolic constituents, as the crucial mechanism controlling this process and
regulating the innate immune response of airway epithelial cells to viral
infection. We will also briefly describe some of the recent insights into the
immune responses of the airway to HRV, focusing on neutrophilic inflammation that
is a potentially unwanted feature of the acute response to viral infection, and
the roles of IL-1 and Pellinos in the regulation of responses to HRV.
PMID- 24355018
TI - Activity and expression of histone acetylases and deacetylases in inflammatory
phenotypes of asthma.
AB - BACKGROUND: Histone acetyltransferases (HATs) and histone deacetylases (HDACs)
regulate gene expression, yet differences in the activity of these enzymes in the
inflammatory phenotypes of asthma are unknown. We hypothesized that neutrophilic
asthma (NA) would be associated with increased HAT and decreased HDAC activity.
OBJECTIVE: To investigate total HAT/HDAC activity and gene expression in isolated
blood monocytes and sputum macrophages from healthy and patients with asthma.
METHODS: Peripheral blood and induced sputum were collected from adults with
asthma (n = 52) and healthy controls (n = 9). Sputum inflammatory cell counts
were performed and asthma inflammatory phenotypes were classified according to
sputum eosinophil and neutrophil cut-off's of > 3% and > 61% respectively.
Peripheral blood monocytes were isolated (n = 61) and sputum macrophages were
isolated from a subgroup of patients with asthma (n = 14), using immunomagnetic
cell separation. RNA and nuclear proteins were extracted and quantified. Enzyme
activity was assessed using fluorescent assays and gene expression of EP300,
KAT2B, CREBBP, and HDACs 1, 2 and 3 were measured by qPCR. RESULTS: There was a
significant inverse association between blood monocyte HAT and HDAC activity (r =
-0.58, P < 0.001). NA was associated with increased blood monocyte HAT enzyme
activity (P = 0.02), decreased HDAC activity (P = 0.03), and increased HAT: HDAC
ratio (P < 0.01) compared with eosinophilic asthma. There were no differences in
gene expression of EP300, KAT2B, CREBBP, or HDACs 1, 2 and 3 in blood monocytes
from subjects with asthma or inflammatory phenotypes of asthma. There was no
effect of inhaled corticosteroid use, poor asthma control, or asthma severity on
HAT/HDAC activities. Sputum macrophages had increased expression of KAT2B in
eosinophilic compared with paucigranulocytic asthma. CONCLUSIONS AND CLINICAL
RELEVANCE: Neutrophilic airway inflammation is associated with increased HAT and
reduced HDAC activity in blood monocytes, demonstrating further systemic
manifestations relating to the altered inflammatory gene transcription profile of
neutrophilic asthma.
PMID- 24355019
TI - Baseline specific IgE levels are useful to predict safety of oral immunotherapy
in egg-allergic children.
AB - BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy
but dose-related reactions are common. OBJECTIVE: To evaluate safety of egg-OIT.
To identify predictors of dose-related reactions. METHODS: Fifty children aged 5
18 underwent egg-OIT after confirming IgE-mediated egg allergy by double-blind
placebo-controlled challenge (DBPCFC). All dose-related reactions over a median
period of 18 months on-OIT (range: 12-28) were registered. Children were
retrospectively divided into three subgroups: (1) children who stopped reacting
to OIT-doses over time (RR, Resolved Reactions); (2) children with ongoing dose
related reactions over the whole period on-OIT (PR, Persistent Reactions); (3)
children who discontinued OIT within induction phase due to frequent reactions
not improved by protocol re-adaptation and medication (ED, Early
Discontinuation). Baseline clinical/immunological parameters associated with
subgroups were investigated. RESULTS: Reactions occurred in 7.6% of doses.
Adrenaline was required in 26% of children. The three subgroups corresponded to
three different safety phenotypes: (1) twenty-four children (48%, RR) experienced
infrequent and mainly mild reactions that resolved over time. None required
adrenaline; (2) seventeen children (34%, PR) experienced more frequent and severe
ongoing reactions over time; (3) nine children (18%, ED) discontinued OIT due to
very frequent and mainly moderate reactions. Early discontinuation was associated
with underlying asthma, higher specific IgE (sIgE) and lower threshold at DBPCFC.
In contrast, lower sIgE and less severe reactions at DBPCFC were associated with
subgroup RR. sIgE showed excellent performance in predicting belonging to
subgroup RR. Levels below the optimal cut-off (ovomucoid-sIgE 8.85 kU/L)
indicated 77% probability of belonging to subgroup RR, whereas levels above it
indicated 95% probability of early discontinuation or ongoing reactions over
time. CONCLUSIONS AND CLINICAL RELEVANCE: Egg-OIT involves substantial risks.
However, baseline parameters, particularly sIgE, may help identify children in
whom the procedure is more likely to be safe. Egg-OIT safety needs improvement in
children with more severe and persistent egg allergy.
PMID- 24355020
TI - Viral respiratory tract infections and asthma in early life: cause and effect?
AB - Interactions between viral respiratory tract infections in infancy and childhood,
and asthma development and exacerbation, are complex and intriguing. This review
aims to unravel some of these complexities. Does severe respiratory viral
infection early in life predispose to later asthma development, or is it
indicative of a predisposition to allergic respiratory disease? How could
variables such as age and severity of viral infection affect the interaction
between respiratory viral infections and asthma? How could respiratory viral
infection drive allergic sensitization? Here, we review the evidence surrounding
these questions, and discuss current and future research and therapeutic
approaches targeting the interplay between viral respiratory tract infection and
asthma.
PMID- 24355021
TI - Triage performance of Swedish physicians using the ATLS algorithm in a simulated
mass casualty incident: a prospective cross-sectional survey.
AB - BACKGROUND: In a mass casualty situation, medical personnel must rapidly assess
and prioritize patients for treatment and transport. Triage is an important tool
for medical management in disaster situations. Lack of common international and
Swedish triage guidelines could lead to confusion. Attending the Advanced Trauma
Life Support (ATLS) provider course is becoming compulsory in the northern part
of Europe. The aim of the ATLS guidelines is provision of effective management of
single critically injured patients, not mass casualties incidents. However, the
use of the ABCDE algorithms from ATLS, has been proposed to be valuable, even in
a disaster environment. The objective for this study was to determine whether the
mnemonic ABCDE as instructed in the ATLS provider course, affects the ability of
Swedish physician's to correctly triage patients in a simulated mass casualty
incident. METHODS: The study group included 169 ATLS provider students from 10
courses and course sites in Sweden; 153 students filled in an anonymous test just
before the course and just after the course. The tests contained 3 questions
based on overall priority. The assignment was to triage 15 hypothetical patients
who had been involved in a bus crash. Triage was performed according to the ABCDE
algorithm. In the triage, the ATLS students used a colour-coded algorithm with
red for priority 1, yellow for priority 2, green for priority 3 and black for
dead. The students were instructed to identify and prioritize 3 of the most
critically injured patients, who should be the first to leave the scene. The same
test was used before and after the course. RESULTS: The triage section of the
test was completed by 142 of the 169 participants both before and after the
course. The results indicate that there was no significant difference in triage
knowledge among Swedish physicians who attended the ATLS provider course. The
results also showed that Swedish physicians have little experience of real mass
casualty incidents and exercises. CONCLUSION: The mnemonic ABCDE doesn't
significantly affect the ability of triage among Swedish physicians. Actions to
increase Swedish physicians' knowledge of triage, within the ATLS context or
separately, are warranted.
PMID- 24355022
TI - Laparoscopic surgery for rectal cancer: current status and future perspective.
AB - Although laparoscopic surgery for colon cancer is accepted in the treatment
guidelines, the laparoscopic approach for rectal cancer is recommended only in
clinical trials. Thus far, several trials have shown favorable short-term results
such as early recovery and short hospital stay, but long-term results remain a
critical concern for laparoscopic rectal cancer surgery. To date, no randomized
control trials have shown an increased local recurrence after laparoscopic
surgery for rectal cancer. Additionally, according to previous studies, open
conversion, which is more frequent in laparoscopic rectal surgery than in
laparoscopic colon surgery, may affect short-term and long-term survival. The
evidence on male sexual function has been contradictory. Long-term results from
ongoing multicenter trials will be available within several years. Based on
accumulated evidence from well-organized clinical trials, laparoscopic surgery
will likely be accepted as a treatment choice for rectal cancer. In the future,
extended laparoscopic rectal surgery might be feasible for additional procedures
such as laparoscopic lateral pelvic lymph node dissection and laparoscopic total
pelvic exenteration for rectal cancer invading the adjacent pelvic organ.
PMID- 24355023
TI - Histological and molecular characterization of the femoral attachment of the
human ligamentum capitis femoris.
AB - The ligamentum capitis femoris (LCF) has increased in clinical significance
through the development of hip arthroscopy. The histological pathologies and
molecular composition of the femoral attachment of the LCF and the degeneration
caused by LCF disruption were investigated in the human hip joint. Twenty-four
LCFs were retrieved at surgery for femoral neck fracture (age range: 63-87
years). In the "intact" (i.e., intact throughout its length, n = 12) group, the
attachment consisted of rich fibrocartilage. Fibrocartilage cells were present in
the midsubstance. In contrast, the construction of the attachment in the
"disrupted" (i.e., ligament no longer attached to the femoral head, n = 12) group
had disappeared. The attachment in the disrupted group was not labeled for type
II collagen or aggrecan, while that in the intact group was labeled for types I,
II and III collagen, chondroitin 4-sulfate, chondroitin 6-sulfate, aggrecan, and
versican. The percentage of single-stranded DNA-positive chondrocytes was
significantly higher in the disrupted group than in the intact group. We conclude
that the femoral attachment of the LCF has a characteristic fibrocartilaginous
structure that is likely to adjust to the mechanical load, and suggest that its
degeneration is advanced by disruption and should be regarded as a clinical
pathology.
PMID- 24355024
TI - A wake-up call for polio eradication.
PMID- 24355025
TI - Open source clinical science for emerging infections.
PMID- 24355026
TI - Vector control to eliminate artemisinin resistant malaria in the Greater Mekong
subregion.
PMID- 24355028
TI - Lyme disease vaccination: safety first.
PMID- 24355029
TI - Lyme disease vaccination: safety first - authors' reply.
PMID- 24355030
TI - Lyme disease vaccination: safety first - author's reply.
PMID- 24355031
TI - Atazanavir-based therapy with pegylated interferon and ribavirin for patients
with hepatitis C and HIV.
PMID- 24355032
TI - Towards national and global measurement of antiretroviral therapy effectiveness.
PMID- 24355033
TI - A tribute to Professor Peter Martins Ndumbe.
PMID- 24355034
TI - Clustering patterns of human papillomavirus infections among HIV-positive women
in Kenya.
AB - BACKGROUND: HIV-positive women are at increased risk of human papillomavirus
(HPV) infection, and, especially, multiple infections compared to HIV-negative
women. Whether certain HPV types have a tendency to cluster in multiple
infections beyond or below what would be expected by shared risk factors (e.g.,
sexual behavior and the degree of immunosuppression) is unclear. We, therefore,
investigated clustering patterns of 44 HPV types in HIV-positive women from
Kenya. FINDINGS: HPV status was assessed on cervical scrapings from 498 women
using GP5+/6+ PCR and reverse line blot. Logistic regression was used to model
type-specific HPV positivity, adjusted for age, specific HPV type prevalence,
CD4, combination antiretroviral therapy, and, in the Full Model, individual-level
random effects that represent unobservable risk factors common to all HPV types.
We found a modest excess of women with co-infections with 2 HPV types (1.12; 95%
credible intervals: 1.03-1.21) in the Full Model but no significant associations
of individual types. No significant deviations of observed/expected counts were
observed for any 2-way combination of HPV types at either the chosen level of
significance, p = 0.00005, or at p = 0.01. Findings were substantially similar
when women with CIN2/3 were excluded and when they were stratified by use of anti
retroviral therapy or CD4 count. CONCLUSIONS: HPV co-infections occurred at
random in the cervix of HIV-positive women as previously found in HIV-negative
women. The removal of HPV types through vaccination should not result, therefore,
in an increase or decrease in the prevalence of HPV types not targeted by
vaccination in immunosuppressed women.
PMID- 24355035
TI - Pancreatic ductal adenocarcinoma radiology reporting template: consensus
statement of the society of abdominal radiology and the american pancreatic
association.
AB - Pancreatic ductal adenocarcinoma is an aggressive malignancy with a high
mortality rate. Proper determination of the extent of disease on imaging studies
at the time of staging is one of the most important steps in optimal patient
management. Given the variability in expertise and definition of disease extent
among different practitioners as well as frequent lack of complete reporting of
pertinent imaging findings at radiologic examinations, adoption of a standardized
template for radiology reporting, using universally accepted and agreed on
terminology for solid pancreatic neoplasms, is needed. A consensus statement
describing a standardized reporting template authored by a multi-institutional
group of experts in pancreatic ductal adenocarcinoma that included radiologists,
gastroenterologists, and hepatopancreatobiliary surgeons was developed under the
joint sponsorship of the Society of Abdominal Radiologists and the American
Pancreatic Association. Adoption of this standardized imaging reporting template
should improve the decision-making process for the management of patients with
pancreatic ductal adenocarcinoma by providing a complete, pertinent, and accurate
reporting of disease staging to optimize treatment recommendations that can be
offered to the patient. Standardization can also help to facilitate research and
clinical trial design by using appropriate and consistent staging by means of
resectability status, thus allowing for comparison of results among different
institutions.
PMID- 24355036
TI - Manufacturer changes lead to clinically important differences between two
editions of the TNO stereotest.
AB - PURPOSE: Stereoacuity tests used in clinical practice should be repeatable and
reproducible. However, it has been observed in a clinical setting that new
editions of the TNO stereotest appear to give different values from those
obtained using previous versions. The purpose of the present research was to
investigate this observation. METHODS: One hundred and twenty-one Dutch subjects,
88 (73%) females and 33 (27%) males, with an average age of 34.0 years (range 18
55) had their stereoacuity measured using two different versions of the TNO
stereoacuity test (TNO 13 and TNO 15). The TNO was tested in a counterbalanced
order so that consecutive subjects started with alternate editions to avoid bias.
RESULTS: There was a significant difference (p < 0.001) between the median value
for stereoacuity measured with TNO 13 (30 s of arc) and TNO 15 (60 s of arc). The
bias between the two test versions was -0.23 Log arcseconds (95% limits of the
differences: 0.15 to -0.60 Log arcseconds). CONCLUSION: This study reveals that
results obtained with two different editions of a commonplace stereoacuity test
are not comparable. New versions come on the market at regular intervals and the
assumption that they will give the same results as previous versions may not be
valid. Besides the statistically significant difference between the TNO 13 and
TNO 15, the Bland-Altman plot also showed a considerable bias and the 95% limits
of the differences between the TNO 13 and TNO 15 are more than two steps on the
Log arcsecond scale. This difference between two editions of the TNO stereotests
is not clinically acceptable and therefore it is inappropriate to use the two
versions of the test interchangeably. It is important in both research and
clinical records to specify the edition of the TNO test used.
PMID- 24355037
TI - Usefulness of matrix-assisted laser desorption ionisation-time-of-flight mass
spectrometry for identifying clinical Trichosporon isolates.
AB - Trichosporon spp. have recently emerged as significant human pathogens.
Identification of these species is important, both for epidemiological purposes
and for therapeutic management, but conventional identification based on
biochemical traits is hindered by the lack of updates to the species databases
provided by the different commercial systems. In this study, 93 strains, or
isolates, belonging to 16 Trichosporon species were subjected to both molecular
identification using IGS1 gene sequencing and matrix-assisted laser desorption
ionisation-time-of-flight (MALDI-TOF) analysis. Our results confirmed the limits
of biochemical systems for identifying Trichosporon species, because only 27
(36%) of the isolates were correctly identified using them. Different protein
extraction procedures were evaluated, revealing that incubation for 30 min with
70% formic acid yields the spectra with the highest scores. Among the six
different reference spectra databases that were tested, a specific one composed
of 18 reference strains plus seven clinical isolates allowed the correct
identification of 67 of the 68 clinical isolates (98.5%). Although until recently
it has been less widely applied to the basidiomycetous fungi, MALDI-TOF appears
to be a valuable tool for identifying clinical Trichosporon isolates at the
species level.
PMID- 24355038
TI - Information asymmetry, social networking site word of mouth, and mobility effects
on social commerce in Korea.
AB - The purpose of this research is to examine the issues that affect customers'
behavioral character and purchasing behavior. The study proposes a research
hypothesis with independent variables that include social presence, trust, and
information asymmetry, and the dependent variable purchase decision making, to
explain differentiated customer decision making processes in social commerce (S
commerce). To prove the hypothesis, positive verification was performed by
focusing on mediating effects through a customer uncertainty variable and
moderating effects through mobility and social networking site word of mouth (SNS
WOM) variables. The number of studies on customer trends has rapidly increased
together with the market size of S-commerce. However, few studies have examined
the negative variables that make customers hesitant to make decisions in S
commerce. This study investigates the causes of customer uncertainty and focuses
on deducing the control variables that offset this negative relationship. The
study finds that in customers' S-commerce purchasing actions, the SNS WOM and
mobility variables show control effects between information asymmetry and
uncertainty and between trust and uncertainty. Additionally, this research
defines the variables related to customer uncertainty that are hidden in S
commerce, and statistically verifies their relationship. The research results can
be used in Internet marketing practices to establish marketing mix strategies for
customer demand or as research data to predict customer behavior. The results are
scientifically meaningful as a precedent for research on customers in S-commerce.
PMID- 24355039
TI - Effects of the body mass index on menopausal symptoms among Asian American
midlife women using two different classification systems.
AB - OBJECTIVE: To explore the effects of the body mass index (BMI) on menopausal
symptoms among Asian American midlife women using two different classification
systems: the international classification and the BMI classification for public
health action among Asian populations. DESIGN: Secondary analysis using data from
two large Internet survey studies. SETTING: Communities and groups of midlife
women on the Internet. PARTICIPANTS: A total of 223 Asian American midlife women
who were recruited over the Internet. METHODS: The Midlife Women's Symptom Index
and self-reports of height and weight were used to collect data. The data were
analyzed using multiple analyses of covariance. RESULTS: No significant
differences in the prevalence and severity scores among three subscales and total
menopausal symptoms according to the international classification were found.
When the BMI classification for public health action among Asian populations was
used as an independent variable, significant differences were found in the
severity scores of three subscales and total menopausal symptoms. Results of the
post-hoc analyses showed that Asian American midlife women who were in the BMI
classification for high risk had significantly more severe menopausal symptoms
than those who were in the BMI classification for increased risk. CONCLUSION: For
Asian American women, BMI categorized using the BMI classification for Asian
populations is more closely related to the severity of menopausal symptoms than
BMI categorized using the international classification. Nurses need to consider
the BMI classification for Asian populations when they develop interventions to
prevent and alleviate menopausal symptoms among Asian American midlife women.
PMID- 24355040
TI - The response to testosterone undecanoate in men with type 2 diabetes is dependent
on achieving threshold serum levels (the BLAST study).
AB - BACKGROUND: The association between testosterone deficiency and insulin
resistance in men with type 2 diabetes is well established. Current Endocrine
Society and European Association of Urology guidelines recommend the measurement
of testosterone levels in all men with type 2 diabetes and in men suffering from
erectile dysfunction. It is recognised that a range of physical symptoms appear
as the testosterone level falls but few studies have addressed the threshold at
which symptoms improve with physiological replacement. We report the first double
blind placebo-controlled study conducted exclusively in a male type 2 diabetes
population to assess the metabolic changes with testosterone replacement.
METHODS: The type 2 diabetes registers of seven general practices were screened
to establish the prevalence of low testosterone and the associations with
diabetes control. Of 550 eligible patients approached, 488 men (mean age 62.6)
consented to take part in screening with a morning testosterone level, assessed
between 8 and 11 am. This identified 211 patients for a double-blind placebo
controlled study of long acting testosterone undecanoate (TU) 1000 mg lasting 30
weeks followed by 52 weeks of open label use. The population was divided into a
SEVERE group with either total testosterone (TT) of 8 nmol/l or less or free
testosterone (FT) 180 pmol/l or less or a MILD group with TT 8.1-12 nmol/l or FT
181-250 pmol/l. RESULTS: Men in the SEVERE group increased mean through TT from
7.73 nmol/l at baseline to 9.93 at 30 weeks and the MILD group from 10.47 to
11.94. The SEVERE group showed marked improvement in sexual function, but no
significant improvement in metabolic parameters. The MILD group showed no
improvement in sexual function, but significant improvement in weight, body mass
index, waist circumference and Hospital Anxiety and Depression Scale. Improvement
was seen in all parameters during 52 weeks open label treatment where trough TT
levels approached 15 nmol/l. Baseline prostate-specific antigen (PSA) was lower
in the SEVERE group and increased with TU for 30 weeks and then stabilised. There
was no increase in PSA with treatment in the MILD group. CONCLUSIONS:
Testosterone undecanoate significantly improves sexual parameters and Ageing Male
Symptom Score, but not metabolic factors at 30 weeks in men with SEVERE
testosterone deficiency syndrome (TDS). In men with MILD TDS, significant
improvements in metabolic but not sexual parameters were seen, suggesting that
there are threshold levels for response to testosterone replacement therapy and
that trials of therapy need to achieve sustained therapeutic levels to be
effective. PSA showed minor rises, but only for 30 weeks in the SEVERE group.
PMID- 24355042
TI - Association of five common polymorphisms in the plasminogen activator inhibitor-1
gene with primary ovarian insufficiency.
AB - OBJECTIVE: To investigate the association between potentially functional
plasminogen activator inhibitor-1 (PAI-1) genetic polymorphisms and primary
ovarian insufficiency (POI). DESIGN: Case-control study. SETTING: Urban
university-based hospital. PATIENT(S): A cohort of 137 POI patients and 227
controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotyping of five PAI
1 polymorphisms (-844G>A [rs2227631], -675 4G/5G [rs1799889], 43G>A (Ala>Thr)
[rs6092], 9785G>A [rs2227694], and 11053T>G [rs7242]) was assessed by polymerase
chain reaction-restriction fragment length polymorphism assay. RESULT(S): PAI-1
polymorphisms 9785GA+AA, -844A/9785A, 4G/9785A, and 9785A/11053G were associated
with POI occurrence. Moreover, -844GA+AA and 11053TG+GG were associated with
lower serum E2 levels in controls. CONCLUSION(S): We have identified an
association between five PAI-1 polymorphisms and POI occurrence. However, the
mechanism underlying the function of these polymorphisms in POI remains to be
determined. Further studies are needed to improve understanding of the roles of
PAI-1 polymorphisms and genes in related pathways, using a larger and more
heterogeneous cohort.
PMID- 24355041
TI - Integrative analyses of gene expression and DNA methylation profiles in breast
cancer cell line models of tamoxifen-resistance indicate a potential role of
cells with stem-like properties.
AB - INTRODUCTION: Development of resistance to tamoxifen is an important clinical
issue in the treatment of breast cancer. Tamoxifen resistance may be the result
of acquisition of epigenetic regulation within breast cancer cells, such as DNA
methylation, resulting in changed mRNA expression of genes pivotal for estrogen
dependent growth. Alternatively, tamoxifen resistance may be due to selection of
pre-existing resistant cells, or a combination of the two mechanisms. METHODS: To
evaluate the contribution of these possible tamoxifen resistance mechanisms, we
applied modified DNA methylation-specific digital karyotyping (MMSDK) and digital
gene expression (DGE) in combination with massive parallel sequencing to analyze
a well-established tamoxifen-resistant cell line model (TAM(R)), consisting of 4
resistant and one parental cell line. Another tamoxifen-resistant cell line model
system (LCC1/LCC2) was used to validate the DNA methylation and gene expression
results. RESULTS: Significant differences were observed in global gene expression
and DNA methylation profiles between the parental tamoxifen-sensitive cell line
and the 4 tamoxifen-resistant TAM(R) sublines. The 4 TAM(R) cell lines exhibited
higher methylation levels as well as an inverse relationship between gene
expression and DNA methylation in the promoter regions. A panel of genes,
including NRIP1, HECA and FIS1, exhibited lower gene expression in resistant vs.
parental cells and concurrent increased promoter CGI methylation in resistant vs.
parental cell lines. A major part of the methylation, gene expression, and
pathway alterations observed in the TAM(R) model were also present in the
LCC1/LCC2 cell line model. More importantly, high expression of SOX2 and
alterations of other SOX and E2F gene family members, as well as RB-related
pocket protein genes in TAMR highlighted stem cell-associated pathways as being
central in the resistant cells and imply that cancer-initiating cells/cancer stem
like cells may be involved in tamoxifen resistance in this model. CONCLUSION: Our
data highlight the likelihood that resistant cells emerge from cancer-initiating
cells/cancer stem-like cells and imply that these cells may gain further
advantage in growth via epigenetic mechanisms. Illuminating the expression and
DNA methylation features of putative cancer-initiating cells/cancer stem cells
may suggest novel strategies to overcome tamoxifen resistance.
PMID- 24355043
TI - Angled vas cutter for vasovasostomy: technique and results.
AB - OBJECTIVE: To describe the technique and results of bilateral vasovasostomy using
a 3-mm vas cutting forceps angled at 15 degrees (catalog no. NHF-3.15; ASSI) for
vasal transection. DESIGN: Retrospective chart review. Institutional review board
approval was granted by Western Institutional Review Board. SETTING: Single
vasectomy reversal center. PATIENT(S): Men who underwent a bilateral
vasovasostomy at a single institution by a single surgeon between 2001 and 2012
and had a minimum of one semen analysis postoperatively or a reported natural
conception. INTERVENTION(S): Before September 14, 2010, a straight-edge vas
cutter was used on all vasovasostomy connections; 375 men received a bilateral
vasovasostomy and met follow-up criteria. Beginning on September 14, 2010, an
angled cutter was used on all vasovasostomy patients, with 194 men meeting the
exclusion criteria. MAIN OUTCOME MEASURE(S): A minimum of 1 * 10(6) sperm
reported on a postoperative semen analysis, or a reported natural conception was
used to establish patency. RESULT(S): The overall vasovasostomy patency rate
using the angled vas cutter was 99.5% and was 95.7% using the straight vas
cutter. CONCLUSION(S): The development of an angled vas cutter provides an
increased surface area for vasal wound healing to allow for larger tissue
diameter for better healing, resulting in high patency rates after vasovasostomy.
PMID- 24355044
TI - Rat bone marrow mesenchymal stem cells improve regeneration of thin endometrium
in rat.
AB - OBJECTIVE: To investigate whether bone marrow mesenchymal stem cell (BMSC)
treatment could improve the regeneration of endometrium and improve the
endometrial receptivity in an experimental model of thin endometrium. DESIGN:
Randomized, control trial, animal research. SETTING: National key laboratory.
ANIMAL(S): Sprague-Dawley rats. INTERVENTION(S): Bone marrow mesenchymal stem
cell transplantation by tail vein IV injection. MAIN OUTCOME MEASURE(S):
Endometrial thickness, the expression of mark proteins for endometrial cell, and
endometrial receptivity. RESULT(S): The endometrium was significantly thicker and
the expression of cytokeratin, vimentin, integrin alphagammabeta3, and leukemia
inhibitor factor were significantly stronger compared with the control group.
Some proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha)
messenger RNA (mRNA) and interleukin-1beta mRNA, were significantly down
regulated, and anti-inflammatory cytokines, such as fibroblast growth factor-beta
(bFGF) mRNA and interleukin-6 mRNA, were significantly up-regulated in the
experimental group compared with the control group. CONCLUSION(S): The BMSCs have
beneficial effect on thin endometrium, and may play a role through migration and
immunomodulatory of BMSCs.
PMID- 24355045
TI - The nature of aneuploidy with increasing age of the female partner: a review of
15,169 consecutive trophectoderm biopsies evaluated with comprehensive
chromosomal screening.
AB - OBJECTIVE: To determine the relationship between the age of the female partner
and the prevalence and nature of human embryonic aneuploidy. DESIGN:
Retrospective. SETTING: Academic. PATIENT(S): Trophectoderm biopsies.
INTERVENTION(S): Comprehensive chromosomal screening performed on patients with
blastocysts available for biopsy. MAIN OUTCOME MEASURE(S): Evaluation of the
impact of maternal age on the prevalence of aneuploidy, the probability of having
no euploid embryos within a cohort, the complexity of aneuploidy as gauged by the
number of aneuploid chromosomes, and the trisomy/monosomy ratio. RESULT(S):
Aneuploidy increased predictably after 26 years of age. A slightly increased
prevalence was noted at younger ages, with >40% aneuploidy in women 23 years and
under. The no euploid embryo rate was lowest (2% to 6%) in women aged 26 to 37,
was 33% at age 42, and was 53% at age 44. Among the biopsies with aneuploidy, 64%
involved a single chromosome, 20% two chromosomes, and 16% three chromosomes,
with the proportion of more complex aneuploidy increasing with age. Finally, the
trisomy/monosomy ratio approximated 1 and increased minimally with age.
CONCLUSION(S): The lowest risk for embryonic aneuploidy was between ages 26 and
30. Both younger and older age groups had higher rates of aneuploidy and an
increased risk for more complex aneuploidies. The overall risk did not measurably
change after age 43. Trisomies and monosomies are equally prevalent.
PMID- 24355046
TI - Fertility in patients with congenital adrenal hyperplasia.
AB - Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic
steroid disorder affecting fertility. Steroid hormones play a crucial role in
sexual development and reproductive function; patients with either 21-
hydroxylase or 11beta-hydroxylase deficiency thus face immense challenges to
their fertility. Given the relevance of CAH in reproductive medicine as well as
the diagnostic challenges posed by the phenotypic overlap with polycystic ovary
syndrome, we review the reproductive pahophysiology of both classic and
nonclassic CAH and present contemporary treatment options.
PMID- 24355047
TI - Unilateral oophorectomy results in compensatory follicular recruitment in the
remaining ovary at time of ovarian stimulation for in vitro fertilization.
AB - OBJECTIVE: To assess the effect of unilateral oophorectomy (UO) by assessing
ovarian reserve (OVR) and the response to gonadotropin stimulation in women with
UO undergoing in vitro fertilization (IVF) compared with the response of the
ipsilateral ovary of women without UO. DESIGN: Historical cohort study. SETTING:
Academic fertility clinic. PATIENT(S): Fifty-one women with single ovary compared
with a referent group with both ovaries in a 1:2 fashion. INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Day-3 follicle-stimulating hormone (FSH), estradiol, and
antral follicle counts as measures of OVR, and IVF outcomes including number of
follicles aspirated and oocytes retrieved. RESULT(S): The baseline demographics
and serum markers of OVR were not different. Referent women had greater
follicular yield and oocyte numbers when compared with women with UO; however,
when compared with the ipsilateral ovary of the referents, women with UO had a
higher antral follicle count and greater follicle and oocyte numbers. In
multivariate analyses, the ovary from women with UO was more likely to yield more
than the median number of follicles and oocytes than the ipsilateral ovary in
referent women. Live-birth rates in both groups were similar. CONCLUSION(S): Our
results suggest that the remaining ovary appears to compensate in follicular
yield after UO in women, confirming the animal data. Women with UO can be
reassured and appropriately counseled regarding IVF.
PMID- 24355048
TI - Complete method to obtain, culture, and transfer mouse blastocysts nonsurgically
to study implantation and development.
AB - OBJECTIVE: To illustrate an efficient, complete, step-by-step protocol for
studying implantation in mice. DESIGN: Video presentation of an animal model for
research in reproductive biology. ANIMAL(S): Mouse (Mus musculus).
INTERVENTION(S): A nonsurgical embryo transfer system very similar to that used
for human embryo transfer. MAIN OUTCOME MEASURE(S): The protocols with recipient
and donor mice are performed in parallel in the same week. For the donor mice:
the first step is ovarian stimulation, followed by ovulation induction and
mating; finally, the mice are sacrificed, and the embryos are collected and
cultured. For recipient mice: first estrous synchrony is induced, followed by
mating with a vasectomized male, visualization of the vaginal plug, and
nonsurgical transfer of the embryos. Finally (optionally), the implantation sites
can be visualized on day 7.5 of development. (All animal experiments were
performed with the approval of the institutional review board.) RESULT(S):
Implantation is an essential step in human reproduction although, because of
technical and ethics considerations, still relatively little is known about human
implantation and early development. Conversely, mouse models are well established
and can be used for preliminary experiments. However, there are various
bottlenecks in the procedure for obtaining and transferring murine embryos, which
makes experimentation with this model more difficult. These difficulties include
pseudopregnancy, ovarian hyperstimulation, and embryo collection, culture, and
transfer. We have proposed a complete, efficient method for obtaining, culturing,
and transferring mouse blastocysts that can be easily applied in research.
Potential applications include testing new media components that do not affect
preimplantation but do affect implantation and early development. The embryo
transfer method proposed here has been demonstrated to achieve embryo
implantation easier and faster than, and in approximately similar rates as other
traditional surgery methods. CONCLUSION(S): This workflow is the first set of
complete step-by-step instructions available that incorporate advances such as
nonsurgical mouse embryo transfer. This will facilitate research into different
reproduction events such as embryo development, embryo implantation, or
contraception.
PMID- 24355049
TI - Progesterone level at oocyte retrieval predicts in vitro fertilization success in
a short-antagonist protocol: a prospective cohort study.
AB - OBJECTIVE: To evaluate the distribution of P levels on the day of oocyte
retrieval as it relates to pregnancy outcome in an antagonist protocol, which may
be at higher risk for elevated P levels. DESIGN: Prospective cohort study.
SETTING: Academic IVF center. PATIENT(S): One hundred eighty-six women undergoing
controlled ovarian hyperstimulation with an antagonist protocol. INTERVENTION(S):
None. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and spontaneous abortion
rates were collected. RESULT(S): Implantation rate (positive hCG 14 days after
ET) and pregnancy rate were significantly higher when the P level was <12 ng/mL
on the day of oocyte retrieval. Miscarriage rates were higher when the P level
was >=12 ng/mL, although this did not reach statistical significance.
CONCLUSION(S): Elevated P on the day of oocyte retrieval is associated with
significantly lower implantation and ongoing pregnancy rates. This is the first
study to date to both uncover the distribution of P on the day of oocyte
retrieval in an antagonist cycle and determine the impact an elevation may have
on pregnancy outcome.
PMID- 24355051
TI - Type 2 deiodinase Thr92Ala polymorphism is associated with disrupted placental
activity but not with dysglycemia or adverse gestational outcomes: a genetic
association study.
AB - OBJECTIVE: To study whether the D2 Thr92Ala polymorphism-a genetic marker that is
associated with reduced thyroid type 2 deiodinase (D2) activity, increased
insulin resistance, and risk for type 2 diabetes-is associated with disrupted
placental D2 activity and with glycemic control and gestational outcomes. DESIGN:
Cross-sectional study. SETTING: Tertiary hospital in Brazil. PATIENT(S):
Consecutive singleton-pregnancy patients, 18-45 years old. INTERVENTION(S):
Clinical examination and genotyping of the D2 Thr92Ala polymorphism, with
placental samples collected and assayed for D2 mRNA and activity. MAIN OUTCOME
MEASURE(S): Glucose homeostasis and gestational outcomes. RESULT(S): A total of
294 patients were included in the study. The clinical and laboratory
characteristics were similar among the D2 genotypes. No differences were observed
in D2 placental mRNA levels, but D2 activity was decreased in patients with the
Ala92Ala genotype (0.35 +/- 0.15 vs. 1.96 +/- 1.02 fmol/mg/min.). Newborn serum
thyroid-stimulating hormone levels (TSHneo) did not differ according to maternal
D2 Thr92Ala genotype. Also, maternal glucose control, insulin resistance
evaluated by the homeostasis model assessment (HOMA-IR), and gestational outcomes
did not differ across D2 genotypes. CONCLUSION(S): The D2 Ala92Ala genotype is
associated with reduced placental D2 activity but is not associated with
dysglycemia, increased insulin resistance, or worse gestational outcomes.
PMID- 24355052
TI - Methotrexate treatment of ectopic pregnancies does not affect ovarian reserve in
in vitro fertilization patients.
PMID- 24355050
TI - Female dietary antioxidant intake and time to pregnancy among couples treated for
unexplained infertility.
AB - OBJECTIVE: To determine whether increased antioxidant intake in women is
associated with shorter time to pregnancy (TTP) among a cohort of couples being
treated for unexplained infertility. DESIGN: Secondary data analysis of a
randomized controlled trial. SETTING: Academic medical center associated with a
private infertility center. PATIENTS: Females with unexplained infertility.
INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The time it took to establish a
pregnancy that led to a live birth. RESULT(S): Mean nutrient intake exceeded the
estimated average requirement (EAR) for vitamins C and E. No differences in mean
intake of any of the antioxidants were noted between women who delivered a live
born infant during the study period vs. those who did not. In multivariable
models, intake of beta-carotene from dietary supplements was associated with
shorter TTP among women with body mass index (BMI) >=25 kg/m(2) (hazard ratio
[HR] 1.29, 95% confidence interval [CI] 1.09-1.53) and women <35 y (HR 1.19, 95%
CI 1.01-1.41). Intake of vitamin C from dietary supplements was associated with
shorter TTP among women with BMI <25 kg/m(2) (HR 1.09, 95% CI 1.03-1.15) and
women <35 y (HR 1.10, 95% CI 1.02-1.18). Intake of vitamin E from dietary
supplements among women >=35 y also was associated with shorter TTP (HR 1.07, 95%
CI 1.01-1.13). CONCLUSION(S): Shorter TTP was observed among women with BMI <25
kg/m(2) with increasing vitamin C, women with BMI >=25 kg/m(2) with increasing
beta-carotene, women <35 y with increasing beta-carotene and vitamin C, and women
>=35 y with increasing vitamin E. CLINICAL TRIAL REGISTRATION NUMBER:
NCT00260091.
PMID- 24355053
TI - Chromosome size, morphology, and gene density determine bivalent positioning in
metaphase I human spermatocytes.
AB - OBJECTIVE: To determine whether there is a preferential bivalent distribution
pattern in metaphase I human spermatocytes and to analyze whether this
positioning is influenced by chiasmata count, chromosome size, gene density,
acrocentric morphology, and heterochromatic blocks. DESIGN: Proximity frequencies
of bivalents were evaluated with the analysis of meiotic preparations combining
sequentially standard techniques and multiplex fluorescence in situ
hybridization. SETTING: University. PATIENT(S): Twenty-five men consulting for
fertility problems. INTERVENTION(S): Unilateral testicular biopsies. MAIN OUTCOME
MEASURE(S): Proximity analyses were performed for each bivalent considering as
nearby bivalents those that were part of the first ring around the bivalent
studied. Data were analyzed using Poisson regression models, multidimensional
scaling, and cluster analysis. RESULT(S): Some bivalents have a preferential
relative position. Significant associations among bivalents related to chromosome
size, high gene density, and acrocentric morphology were observed. Chiasmata
count and heterochromatic blocks were nonconditioning parameters of the bivalent
organization. CONCLUSION(S): This study demonstrates that distribution in
metaphase I is nonrandom and influenced by chromosome size, gene density, and
acrocentric chromosome morphology. Results support that some features defining
chromosome territories are maintained during meiosis.
PMID- 24355054
TI - Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy
outcomes after in vitro fertilization.
AB - OBJECTIVE: To determine whether serum hyperglycosylated human chorionic
gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict
ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF
ET). DESIGN: Cohort SETTING: Academic assisted reproduction center. PATIENT(S):
Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels
measured 9 (D9) and 16 (D16) days after egg retrieval MAIN OUTCOME MEASURE(S):
Ongoing pregnancy beyond 9 weeks of gestation. RESULT(S): Ongoing pregnancy (62
of 112 participants) was associated with higher D9 levels of hhCG and hCG.
However, hhCG was detectable in all D9 OP samples, while hCG was detectable in
only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing
pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG
levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs.
0.67, respectively). The diagnostic test characteristics were similar between the
D16 hhCG and hCG levels. CONCLUSION(S): In patients undergoing assisted
reproduction, a test to detect pregnancy early and predict outcomes is highly
desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET
cycles. In this early assessment, hhCG was superior to traditional hCG and highly
predictive of ongoing pregnancies.
PMID- 24355055
TI - Measurement of antimullerian hormone: not as straightforward as it seems.
PMID- 24355056
TI - Exploring facilitating factors and barriers to the nationwide dissemination of a
Dutch school-based obesity prevention program "DOiT": a study protocol.
AB - BACKGROUND: The evidence-based Dutch Obesity Intervention in Teenagers (DOiT)
program is a school-based obesity prevention program for 12 to 14-year olds
attending the first two years of prevocational education. This paper describes
the study protocol applied to evaluate (a) the nationwide dissemination process
of DOiT in the Netherlands, and (b) the relationship between quality of
implementation and effectiveness during nationwide dissemination of the program
in the Netherlands. METHODS: In order to explore facilitating factors and
barriers for dissemination of DOiT, we monitored the process of adoption,
implementation and continuation of the DOiT program among 20 prevocational
schools in the Netherlands. The study was an observational study using
qualitative (i.e. semi-structured interviews) and quantitative methods (i.e.
questionnaires and logbooks). Eight process indicators were assessed:
recruitment, context, reach, dosage, fidelity, satisfaction, effectiveness and
continuation. All teachers, students and parents involved in the implementation
of the program were invited to participate in the study. As part of the process
evaluation, a cluster-controlled trial with ten control schools was conducted to
evaluate the effectiveness of the program on students' anthropometry and energy
balance-related behaviours and its association with quality of implementation.
DISCUSSION: The identified impeding and facilitating factors will contribute to
an adjusted strategy promoting adoption, implementation and continuation of the
DOiT program to ensure optimal use and, thereby, prevention of obesity in Dutch
adolescents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92755979.
PMID- 24355057
TI - Carotid sinus massage in the echocardiography laboratory.
AB - Proper interpretation of the spectral Doppler signal and elucidation of the
underlying hemodynamics can at times be problematic due to confounding factors,
one of them being a rapid heart rate. In this article, we discuss the use of
carotid sinus massage (CSM) in the echocardiography laboratory as a maneuver to
reduce the resting heart rate and thus render the transmitral Doppler signal more
amenable to analysis. We provide examples of the value of the CSM in the
assessment of left ventricular filling pressure.
PMID- 24355058
TI - Exploring the frequency of blood pressure documentation in emergency departments.
AB - PURPOSE: One of the most commonly performed task in the emergency department (ED)
is reported as the monitoring of vital signs, yet there are no published
standards of care that provide guidelines for the frequency of obtaining vital
signs in the ED. The purpose of this exploratory study was to determine the
frequency of documentation of vital signs recorded during ED visits across
Veterans Health Administration (VHA) facilities. METHODS: Deidentified patient
level data from the VHA electronic health record (EHR) were abstracted for
emergency department visits for 12 randomly selected days in calendar year 2011.
The dataset included vital signs data, associated time stamps, facility, length
of stay, triage category based on the Emergency Severity Index (ESI), and patient
disposition for all patients. Descriptive statistics were used to describe the
frequency of the specific vital sign measures, and parametric and nonparametric
tests were used to examine study variables by ESI. FINDINGS: The sample consisted
of over 43,232 unique patient visits to 94 VHA EDs with a median length of stay
of 173.3 min (interquartile range [IQR], 96.1-286.9). The mean number of times
that blood pressure (BP) was recorded per visit was 1.23 (SD 1.175). For the
entire sample, median time between blood pressure measurements was 139.7 min
(IQR, 81.6-230.1). There was a significant difference in median length of stay
and median time between blood pressure by ESI category. CONCLUSIONS: In this
dataset, median time between documentation of BP in the ED was every 2.3 hr for
all patients. While the median time was statistically significant between ESI
categories, these times may not be clinically relevant. More important was the
inconsistent documentation of vital signs of ED patients in the designated fields
in the EHR. Most facilities (84.1%) documented BP for >75% of patient visits.
However, eight facilities (9.1%) had BP documented in <50% of patient visits.
CLINICAL RELEVANCE: It seems unlikely that vital signs are not monitored in the
ED; nurses anecdotally report that vital signs are recorded on a paper chart and
later scanned as an image into the EHR. However, lack of consistent process in
documentation of vital signs may decrease the care team's ability to note early
warning signs of physiological instability or deterioration.
PMID- 24355059
TI - Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates.
AB - Bulged DNA structures are of general biological significance because of their
important roles in a number of biochemical processes. Compounds capable of
targeting bulged DNA sequences can be used as probes for studying their role in
nucleic acid function, or could even have significant therapeutic potential. The
interaction of [Fe(2)L(3)](4+) metallosupramolecular helicates (L =
C(25)H(20)N(4)) with DNA duplexes containing bulges has been studied by
measurement of the DNA melting temperature and gel electrophoresis. This study
was aimed at exploring binding affinities of the helicates for DNA bulges of
various sizes and nucleotide sequences. The studies reported herein reveal that
both enantiomers of [Fe(2)L(3)](4+) bind to DNA bulges containing at least two
unpaired nucleotides. In addition, these helicates show considerably enhanced
affinity for duplexes containing unpaired pyrimidines in the bulge and/or
pyrimidines flanking the bulge on both sides. We suggest that the bulge creates
the structural motif, such as the triangular prismatic pocket formed by the
unpaired bulge bases, to accommodate the [Fe(2)L(3)](4+) helicate molecule, and
is probably responsible for the affinity for duplexes with a varying number of
bulge bases. Our results reveal that DNA bulges represent another example of
unusual DNA structures recognized by dinuclear iron(II) ([Fe(2)L(3)](4+))
supramolecular helicates.
PMID- 24355061
TI - Investigating the historic long-term population health impact of the US National
School Lunch Program.
AB - OBJECTIVE: The present research aimed to compare historic participation in the US
National School Lunch Program (NSLP) during childhood and subsequent prevalence
of overweight and obesity among adults at the population level. DESIGN:
Regression models examined cross-sectional, state- and age-based panel data
constructed from multiple sources, including the Behavioural Risk Factor
Surveillance System, US Congressional Record, US Census and the US Department of
Agriculture. Models controlled for cohorts' racial/ethnic composition and state
poverty rates. SUBJECTS: Adult-age cohorts (18-34, 35-49, 50-64 and 18-64 years)
by US state over a 25-year period (1984-2008). SETTING: The cohorts' prevalence
of overweight and obesity was compared with the cohorts' estimated NSLP
participation during schooling (1925-2007; the NSLP began in 1946). RESULTS:
Among adults aged 18-64 years, a one percentage-point increase in estimated NSLP
participation during schooling between 1925 and 2007 was significantly associated
with a 0.29 percentage-point increase in the cohort's later prevalence of
overweight and obesity. Analysis of narrower age cohorts and different schooling
periods produced mixed results. CONCLUSIONS: The NSLP might have influenced
population health historically. Longitudinal analysis of individuals from studies
now underway will likely facilitate more robust conclusions about the NSLP's long
term health impact based on more recent experiences.
PMID- 24355060
TI - A single-item self-report medication adherence question predicts hospitalisation
and death in patients with heart failure.
AB - AIMS AND OBJECTIVES: To determine whether a single-item self-report medication
adherence question predicts hospitalisation and death in patients with heart
failure. BACKGROUND: Poor medication adherence is associated with increased
morbidity and mortality. Having a simple means of identifying suboptimal
medication adherence could help identify at-risk patients for interventions.
DESIGN: We performed a prospective cohort study in 592 participants with heart
failure within a four-site randomised trial. METHODS: Self-report medication
adherence was assessed at baseline using a single-item question: 'Over the past
seven days, how many times did you miss a dose of any of your heart medication?'
Participants who reported no missing doses were defined as fully adherent, and
those missing more than one dose were considered less than fully adherent. The
primary outcome was combined all-cause hospitalisation or death over one year and
the secondary endpoint was heart failure hospitalisation. Outcomes were assessed
with blinded chart reviews, and heart failure outcomes were determined by a
blinded adjudication committee. We used negative binomial regression to examine
the relationship between medication adherence and outcomes. RESULTS: Fifty-two
percent of participants were 52% male, mean age was 61 years, and 31% were of New
York Heart Association class III/IV at enrolment; 72% of participants reported
full adherence to their heart medicine at baseline. Participants with full
medication adherence had a lower rate of all-cause hospitalisation and death
(0.71 events/year) compared with those with any nonadherence (0.86 events/year):
adjusted-for-site incidence rate ratio was 0.83, fully adjusted incidence rate
ratio 0.68. Incidence rate ratios were similar for heart failure
hospitalisations. CONCLUSION: A single medication adherence question at baseline
predicts hospitalisation and death over one year in heart failure patients.
RELEVANCE TO CLINICAL PRACTICE: Medication adherence is associated with all-cause
and heart failure-related hospitalisation and death in heart failure. It is
important for clinicians to assess patients' medication adherence on a regular
basis at their clinical follow-ups.
PMID- 24355062
TI - Radical-assisted chemical doping for chemically derived graphene.
AB - Carrier doping of graphene is one of the most challenging issues that needs to be
solved to enable its use in various applications. We developed a carrier doping
method using radical-assisted conjugated organic molecules in the liquid phase
and demonstrated all-wet fabrication process of doped graphene films without any
vacuum process. Charge transfer interaction between graphene and dopant molecules
was directly investigated by spectroscopic studies. The resistivity of the doped
graphene films was drastically decreased by two orders of magnitude. The
resistivity was improved by not only carrier doping but the improvement in
adhesion of doped graphene flakes. First-principles calculation supported the
model of our doping mechanism.
PMID- 24355063
TI - Quality of post-operative patient handover in the post-anaesthesia care unit: a
prospective analysis.
AB - BACKGROUND: Anaesthesiology plays a key role in promoting safe perioperative
care. This includes the perioperative phase in the post-anaesthesia care unit
(PACU) where problems with incomplete information transfer may have a negative
impact on patient safety and can lead to patient harm. The objective of this
study was to analyse information transfer during post-operative handovers in the
PACU. METHODS: With a self-developed checklist including 59 items the information
transfer during post-operative handovers was documented and subsequently compared
with patient information in anaesthesia records during a 2-month period. RESULTS:
A total number of 790 handovers with duration of 73 +/- 49 s was analysed. Few
items were transferred in most of the cases such as type of surgery (97% of the
cases), regional anaesthesia (94% of the cases) and cardiac instability (93% of
the cases). However, some items were rarely transferred, such as American Society
of Anesthesiologists physical status (7% of the cases), initiation of post
operative pain management (12% of the cases), antibiotic therapy (14% of the
cases) and fluid management (15% of the cases). There was a slight correlation
between amount of information transferred and duration of post-operative
handovers (r = 0.5). CONCLUSION: The study shows that post-operative handovers in
the PACU are in most cases incomplete. It appears useful to optimise the post
operative handover process, for example by implementing a standardised handover
checklist.
PMID- 24355064
TI - HEMA-induced cytotoxicity: oxidative stress, genotoxicity and apoptosis.
AB - Dental resin composites consist of organic polymers with inorganic fillers used
as bonding resins and direct filling materials in dentine adhesives and as
sealing agents for inlays, crowns and orthodontic brackets. Despite various
modifications in the formulation, the chemical composition of composite resins
includes inorganic filler particles and additives, which are incorporated into a
mixture of an organic resin matrix. Among them, 2-hydroxyethylmethacrylate (HEMA)
is one of the most frequently used. Several studies have attempted to clarify the
mechanisms underlying HEMA cytotoxicity. Most of them support the hypothesis that
this compound, once released in the oral environment, increases reactive oxygen
species (ROS) production and oxidative DNA damage through double-strand breaks
evidenced by in vitro presence of micronuclei. As a consequence, the glutathione
detoxifying intracellular pool forms adducts with HEMA through its cysteine motif
and inflammation begins to occur: transcription of early genes of inflammation
such as tumour necrosis factor alpha or inducible cyclooxygenase up to the
secretion of prostaglandins 2. These phenomena are counteracted by N
acetylcysteine (NAC), a nonenzymatic antioxidant, but not by vitamin E or other
antioxidant. Consequently, NAC prevents HEMA-induced apoptosis acting as a direct
ROS scavenger. This minireview collects the most significant papers on HEMA and
tries to make an overview of its cytotoxicity on different cell types and
experimental models.
PMID- 24355065
TI - Fungal air quality in hospital rooms: a case study in Tehran, Iran.
AB - Fungi are usually presented in indoor environments and cause of many diseases.
The aim of this descriptive study was to investigate the level of fungal
contamination in hospital rooms. Sampling was conducted with an Andersen one
stage viable impactor (Quick Take-30) and counting plates containing a fungus
selective medium. A total of 120 air samples from ten hospital environments were
performed. Airborne fungi concentrations were determined 72-120 hours after
sampling. Total mean concentration of detected fungi in the hospital rooms was 55
+/- 56 (mean +/- SD) cfu/m3. The findings of the fungal concentration in the
various hospital rooms revealed different levels of contamination: the lowest
mean counts (37 +/- 17 cfu/m3) were observed in NS 1 (Nursing Stations 1), and
the highest (97 +/- 217 cfu/m3) were reported in Orthopedics Operating Room
(OOR). The most common fungal genus isolated were Penicillium (70%), Aspergillus
(14%), Cladosporium (12%), Alternaria (2%) and others (2%). The obtained results
showed that fungal concentrations in the present study were nearly high and these
conditions should be considered as a risk factor for patients and other persons
in the hospital.
PMID- 24355066
TI - An analysis of conjunctival and periocular venous malformations:
clinicopathologic and immunohistochemical features with a comparison of racemose
and cirsoid lesions.
AB - Vascular tumors (in contrast to dilations or ectasias) of the conjunctiva and
other adnexal tissues are rare, with no previous convincing example of a
congenital, purely venous conjunctival malformation having been described. A 33
year-old man with a previously well-tolerated racemose conjunctival lesion
present from birth developed bothersome symptoms when it underwent multifocal
thrombosis with papillary endothelial cell hyperplasia as part of the process of
thrombotic organization. Conservative subtotal excision with placement of an
amniotic graft led to an acceptable cosmetic appearance, abatement of symptoms,
and retention of full ocular function. Histopathologically, the lesion was
composed of patulous vascular channels with thin walls displaying a negligible
and irregular muscularis, diffuse supportive mural fibrosis, and the absence of
an elastic lamina. Immunohistochemically the endothelial cells were CD31- and
CD34-positive (vascular origin) but D2-40-negative (lymphatic origin). An
associated neovascular capillary bed was not detected. Venous (racemose or grape
like) malformations should be distinguished from: arteriovenous (cirsoid or
twisted) malformations in which the vessels possess thicker and more uniform
muscular walls, some of which are endowed with an elastica; varices (hemorrhoidal
dilations typically of a pre-existent vein); and venous angiomas (noncongenital
lesions acquired in middle life) composed of regularly structured muscular
channels devoid of an elastic lamina. Other conditions not to be confused with
congenital venous malformations include hemorrhagic lymphangiectasia (of Leber),
hemorrhagic lymphangiomas, and complex lymphaticovenous malformations.
PMID- 24355067
TI - Periodic change in phase relationship between target and hand motion during visuo
manual tracking task: behavioral evidence for intermittent control.
AB - When one performs visuo-manual tracking tasks, velocity profile of hand movements
shows discontinuous patterns even if the target moves smoothly. A crucial factor
of this "intermittency" is considerable delay in the sensorimotor feedback loop,
and several researchers have suggested that the cause is intermittent correction
of motor commands. However, when and how the brain monitors task performance and
updates motor commands in a continuous motor task is uncertain. We examined how
tracking error was affected by the timing of target disappearance during a
tracking task. Results showed that tracking error, defined as the average phase
difference between target and hand, varied periodically in all conditions. Hand
preceded target at one specific phase but followed it at another, implying that
motor control was not performed in a temporally uniform manner. Tracking
stability was evaluated by the variance in phase difference, and changed
depending on the timing of target-removal. The variability was larger when target
disappeared around turning points than that when it disappeared around the center
of motion. This shows that visual information at turning points is more
effectively exploited for motor control of sinusoidal target tracking, suggesting
that our brain controls hand movements with intermittent reference to visual
information.
PMID- 24355068
TI - Restoration of degraded agricultural terraces: rebuilding landscape structure and
process.
AB - The restoration of severely degraded cropland to productive agricultural capacity
increases food supply, improves soil and water conservation, and enhances
environmental and ecological services. This article examines the key roles that
long-term maintenance plays in the processes of repairing degraded agricultural
land. Field measurements from Tlaxcala, Mexico stress that restoring agricultural
structures (the arrangements of landforms and vegetation) is alone insufficient.
Instead, an effective monitoring and maintenance regime of agricultural
structures is also crucial if the efforts are to be successful. Consequently,
methods of wildland restoration and agricultural restoration may differ in the
degree to which the latter must plan for and facilitate a sustained human
involvement. An improved understanding of these distinctions is critical for
environmental management as restoration programs that employ the technologies of
intensive agriculture continue to grow in number and scope.
PMID- 24355069
TI - Endocrine autoimmunity in Turner syndrome.
AB - BACKGROUND: Turner syndrome is caused by numeric and structural abnormalities of
the X chromosome. An increased frequency of autoimmunity as well as an elevated
incidence of autoantibodies was observed in Turner patients. The aim of this
study was to conduct a retrospective analysis of the incidence of autoimmunity in
66 Italian patients affected by Turner syndrome. METHODS: Sixty-six unselected
and consecutive Italian Turner patients were recruited. The association between
age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and
of autoantibodies was examined. RESULTS: Out of the 66 Turner patients, 26 had
thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto's thyroiditis
with clinical or subclinical hypothyroidism (21.2%) and 12 patients had
circulating anti-thyroid antibodies, echographic pattern of diffuse
hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by
Graves' disease. We analyzed the overall incidence of thyroid autoimmunity within
the 3 different age groups 0-9.9, 10-19.9 and 20-29.9 years. No statistically
significant difference was observed in the incidence of thyroid autoimmunity
within the age-groups (chi2-test p > 0.05).Out of the 66 patients, 31 patients
had the 45,X karyotype; within this first group 14 out of 31 patients were
affected by autoimmune thyroid disease. A second group of 29 patients included 19
patients with mosaicism, 5 patients with deletions and 5 patients with ring
chromosome; out of these 29 patients 7 were affected by autoimmune thyroid
disease. A third group included 6 patients with X isochromosome; 5 out of 6 were
affected by autoimmune thyroid disease. A statistically significant difference in
the frequency of thyroid autoimmunity within the different karyotype groups was
observed (chi2-test p = 0.0173).When comparing the X isochromosome group with the
pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity
was statistically higher in the X isochromosome group (Fisher exact test p =
0.0315). CONCLUSIONS: Our data confirm a high frequency of thyroid autoimmunity
in Italian Turner patients. Patients with X isochromosome are more prone to
develop thyroid autoimmunity. Further, an early assay of autoantibodies and
monitoring thyroid hormones is fundamental for detecting hypothyroidism earlier
and start adequate replacement therapy.
PMID- 24355070
TI - Feasibility and safety of laparoscopic and endoscopic cooperative surgery for
gastric submucosal tumors, including esophagogastric junction tumors.
AB - BACKGROUND AND AIM: Recently, the use of endoscopic submucosal dissection (ESD)
for gastric submucosal tumor (gSMT) and the development of laparoscopic and
endoscopic cooperative surgery (LECS) have enabled either preservation of the
stomach or minimization of the extent of partial resection. In the present study,
the outcomes following the recent introduction of LECS for gSMT are presented.
The aim of this retrospective study was to evaluate the feasibility and safety of
LECS for gSMT, including esophagogastric junction (EGJ) SMT. METHODS: LECS is
indicated for lesions that have an intragastric growth pattern, or for which
fundusectomy can be avoided despite an extragastric growth pattern. We
retrospectively evaluated the outcome of LECS carried out in 25 patients
including five EGJ SMT. RESULTS: Surgery was completed achieving an R0 resection
rate of 100% with no postoperative complications. Mean tumor size was 32.3 +/-
13.5 mm and mean resected specimen size was 37.6 +/- 13.5 mm. Resection margins
were tumor-free in all cases, with adequate minimum surgical margins, and precise
conclusive diagnosis was achieved with perfect operative specimens. Endoscopic
confirmation of the EGJ enabled the extent of resection to be minimized and the
stomach to be preserved, avoiding fundusectomy. Although there were significant
differences in tumor size and resected specimen size between EGJ SMT and non-EGJ
SMT, there were no significant differences in outcomes of the LECS procedure.
CONCLUSION: LECS is feasible and safe for cases with gSMT including lesions
adjacent to the EGJ.
PMID- 24355071
TI - Persistent enhancement of ethanol drinking following a monosodium glutamate
substitution procedure in C57BL6/J and DBA/2J mice.
AB - Inbred mouse strains such as C57BL/6J (B6) and DBA/2J (D2) and related strains
have been used extensively to help identify genetic controls for a number of
ethanol-related behaviors, including acute intoxication and sensitivity to
repeated exposures. The disparate ethanol drinking behaviors of B6 mice
expressing high-drinking/preference and D2 mice expressing low
drinking/preference have yielded considerable insight into the heritable control
of alcohol drinking. However, the B6-high and D2-low drinking phenotypes are
contrasted with ethanol-conditioned reward-like behaviors, which are robustly
expressed by D2 mice and considerably less expressed by B6 mice. This suggests
that peripheral factors, chiefly ethanol taste, may help drive ethanol drinking
by these and related strains, which complicates mouse genetic studies designed to
understand the relationships between reward-related behaviors and ethanol
drinking. Traditional approaches such as the sucrose/saccharin-substitution
procedure that normally accentuate ethanol drinking in rodents have had limited
success in low drinking/preferring mice such as the D2 line. This may be due to
allelic variations of the sweet taste receptor subunit, expressed by many ethanol
low-drinking/preferring strains, which would limit the utility of these types of
substitution approaches. We have recently shown (McCool & Chappell, 2012) that
monosodium glutamate (MSG), the primary component of umami taste, can be used in
a substitution procedure to initiate ethanol drinking in both B6 and D2 mice that
greatly surpasses that initiated by a more traditional sucrose-substitution
procedure. In this study, we show that ethanol drinking initiated by MSG
substitution in D2 mice, but not sucrose substitution, can persist for several
weeks following removal of the flavor. These findings further illustrate the
utility of MSG substitution to initiate ethanol drinking in distinct mouse
strains.
PMID- 24355072
TI - Prenatal exposure to ethanol during late gestation facilitates operant self
administration of the drug in 5-day-old rats.
AB - Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the
probability of ethanol use and abuse. The present study tested developing rats (5
day-old) in a novel operant technique to assess the degree of ethanol self
administration as a result of prenatal exposure to low ethanol doses during late
gestation. On a single occasion during each of gestational days 17-20, pregnant
rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On
postnatal day 5, pups were tested on a novel operant conditioning procedure in
which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5%
ethanol. Immediately after a 15-min training session, a 6-min extinction session
was given in which operant behavior had no consequence. Pups were positioned on a
smooth surface and had access to a touch-sensitive sensor. Physical contact with
the sensor activated an infusion pump, which served to deliver an intraoral
solution as reinforcement (Paired group). A Yoked control animal evaluated at the
same time received the reinforcer when its corresponding Paired pup touched the
sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal
exposure to ethanol during late gestation. In contrast, operant learning
reflecting ethanol reinforcement did not occur in control animals prenatally
exposed to water only. Similarly, saccharin reinforcement was not affected by
prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal
exposure to a low ethanol dose facilitates operant learning reinforced by
intraoral administration of a low-concentration ethanol solution. This emphasizes
the importance of intrauterine experiences with ethanol in later susceptibility
to drug reinforcement. The present operant conditioning technique represents an
alternative tool to assess self-administration and seeking behavior during early
stages of development.
PMID- 24355073
TI - DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro
inflammatory phenotype that is attenuated by rasagiline.
AB - DJ-1 is an oxidative stress sensor that localizes to the mitochondria when the
cell is exposed to oxidative stress. DJ-1 mutations that result in gene
deficiency are linked to increased risk of Parkinson's disease (PD). Activation
of microglial stress conditions that are linked to PD may result in neuronal
death. We postulated that DJ-1 deficiency may increase microglial neurotoxicity.
We found that down-regulation of DJ-1 in microglia using an shRNA approach
increased cell sensitivity to dopamine as measured by secreted pro-inflammatory
cytokines such as IL-1beta and IL-6. Furthermore, we discovered that DJ-1
deficient microglia had increased monoamine oxidase activity that resulted in
elevation of intracellular reactive oxygen species and nitric oxide leading to
increased dopaminergic neurotoxicity. Rasagaline, a monoamine oxidase inhibitor
approved for treatment of PD, reduced the microglial pro-inflammatory phenotype
and significantly reduced neurotoxicity. Moreover, we discovered that DJ-1
deficient microglia have reduced expression of triggering receptor expressed on
myeloid cells 2 (TREM2), previously suggested as a risk factor for pro
inflammation in neurodegenerative diseases. Further studies of DJ-1-mediated
cellular pathways in microglia may contribute useful insights into the
development of PD providing future avenues for therapeutic intervention
PMID- 24355074
TI - Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis:
analyses of exonic splicing enhancer inactivating mutation.
AB - Farber lipogranulomatosis is a rare autosomal recessive lysosomal storage
disorder caused by mutations in the ASAH1 gene. In the largest ever study, we
identified and characterized ASAH1 mutations from 11 independent Farber disease
(FD) families. A total of 13 different mutations were identified including 1
splice, 1 polypyrimidine tract (PPT) deletion and 11 missense mutations. Eleven
mutations were exclusive to the Indian population. The IVS6+4A>G splice and IVS5
16delTTTTC PPT deletion mutations resulted in skipping of exon 6 precluding
thereby the region responsible for cleavage of enzyme precursor. A missense
mutation (p.V198A) resulted in skipping of exon 8 due to inactivation of an
exonic splicing enhancer (ESE) element. This is the first report of mutations
affecting PPT and ESE in the ASAH1 gene resulting in FD.
PMID- 24355075
TI - Impact of bioaugmentation on biochemical methane potential for wheat straw with
addition of Clostridium cellulolyticum.
AB - Hydrolysis is usually the rate-limited step for methane production from
lignocellulosic substrate. Two bioaugmentation strategies, using the cellulolytic
anaerobic bacteria Clostridium cellulolyticum, were adopted to enhance the
hydrolysis of wheat straw with the purpose of improving the biochemical methane
potential (BMP). Namely, the 24-h-incubated seed (C24S) with cellobiose as carbon
source and the 60-h-incubated seed (WS60S) with wheat straw as carbon source were
respectively used as the bioaugmentation agents. As a result, the BMPs were
respectively 342.5 and 326.3 ml g(-1) VS of wheat straw, with an increase of
13.0% and 7.6% comparing to the no-bioaugmentation BMP of 303.3 ml g(-1) VS. The
result indicates that the anaerobic digestion efficiency can be improved by
bioaugmentation, which therefore may be a promising method for improving methane
production from lignocellulosic substrate.
PMID- 24355077
TI - Hemiconvulsion-Hemiplegia-Epilepsy syndrome associated with inflammatory
degenerative hystopathological findings in child with congenital adrenal
hyperplasia.
AB - Hemiconvulsion-Hemiplegia (HH) syndrome represents an uncommon consequence of
prolonged unilateral clonic or hemiconvulsive status epilepticus in childhood,
usually occurring during a febrile illness, followed by ipsilateral hemiplegia.
The subsequent appearance of focal seizures configures the so called
Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome. The pathogenesis of HH/HHE
syndrome is still unclear. We describe the case of a 4 year-old girl with
congenital adrenal hyperplasia (CAH) whom developed HH/HHE syndrome with drug
resistant seizures at the age of 21 months and underwent left cerebral
hemispherotomy at the age of 3 years and 6 months. Histopathological findings
showed the presence of an underlying inflammatory-degenerative process.
Disregulation of the inflammatory cascade has been proposed as one of the
possible pathogenetic mechanisms underlying HH/HHE syndrome. To our knowledge
however, this is the first report of an association with a histologically
documented inflammatory process. The clinical and histopathological findings of
our reported case lend support to the possible role of inflammation in the
pathogenesis of HH/HHE syndrome.
PMID- 24355078
TI - The association between quality of care and quality of life in long-stay nursing
home residents with preserved cognition.
AB - OBJECTIVES: To assess the overall quality of life of long-stay nursing home
residents with preserved cognition, to examine whether the Centers for Medicare
and Medicaid Service's Nursing Home Compare 5-star quality rating system reflects
the overall quality of life of such residents, and to examine whether residents'
demographics and clinical characteristics affect their quality of life.
DESIGN/MEASUREMENTS: Quality of life was measured using the Participant Outcomes
and Status Measures-Nursing Facility survey, which has 10 sections and 63 items.
Total scores range from 20 (lowest possible quality of life) to 100 (highest).
SETTING/PARTICIPANTS: Long-stay nursing home residents with preserved cognition
(n = 316) were interviewed. RESULTS: The average quality- of-life score was 71.4
(SD: 7.6; range: 45.1-93.0). Multilevel regression models revealed that quality
of life was associated with physical impairment (parameter estimate = -0.728; P =
.04) and depression (parameter estimate = -3.015; P = .01) but not Nursing Home
Compare's overall star rating (parameter estimate = 0.683; P = .12) and not pain
(parameter estimate = -0.705; P = .47). CONCLUSION: The 5-star quality rating
system did not reflect the quality of life of long-stay nursing home residents
with preserved cognition. Notably, pain was not associated with quality of life,
but physical impairment and depression were.
PMID- 24355080
TI - Gut instinct.
AB - Barriers to the use of selective digestive decontamination include concerns about
emergence of resistant organisms, over-estimation of current performance in
preventing ventilator-associated pneumonia (VAP), alternative methods of
preventing VAP, and misunderstanding of mechanisms of action. A definitive
cluster-randomised trial should be undertaken that incorporates practitioner
concerns and effect-size preferences.
PMID- 24355079
TI - A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of
aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis.
AB - BACKGROUND: This study sought to identify the maximum tolerated dose (MTD) of
AT9283, an inhibitor of Aurora kinases A and B, in patients with relapsed or
refractory leukemias. Other endpoints included pharmacokinetics, safety and
tolerability, pharmacodynamics, and preliminary evidence of efficacy. PATIENTS
AND METHODS: AT9283 was administered as a continuous 72-hour infusion every 21
days. Doses were escalated by a standard 3 + 3 design. After the MTD for the 72
hour infusion was identified, infusion duration was increased incrementally to 96
hours and 120 hours. In total, 48 patients received >= 1 cycle of AT9283. Median
age was 61 years (range, 22-86 years); 56% were men; 75% were diagnosed with AML;
and 89% had received >= 3 (up to 16) prior lines of therapy. RESULTS: 324
mg/m(2)/72 h AT9283 was determined to be the MTD. Dose-limiting toxicities (DLTs)
were myocardial infarction, hypertension, cardiomyopathy, tumor lysis syndrome,
pneumonia, and multiorgan failure. Other AT9283-related toxicities (non-DLT)
included myelosuppression, predominantly leukopenia and mucositis. Bone marrow
blasts decreased >= 38% after AT9283 treatment in approximately one-third of
patients with relapsed/refractory AML; however, this effect was transient and no
objective responses were achieved, despite evidence of Aurora kinase B
inhibition. Two patients with accelerated-phase chronic myeloid leukemia showed
evidence of benefit, manifested as a cytogenetic response in 1 case; 1 patient
completed 6 cycles of treatment. Exposure to AT9283 was generally dose
proportional. CONCLUSION: AT9283 tolerability was strongly dose-dependent, with
reversible myelosuppression predominating at lower doses and events such as
cardiovascular toxicities manifesting at higher doses. Clinical trials with
AT9283 are ongoing in alternative patient populations.
PMID- 24355081
TI - Obesity dilemma in the global burden of cardiovascular diseases.
AB - AIM: Obesity is a well-known risk factor in the cardiovascular disease continuum.
However, its clinical effects are multimodal, perplexed and non-unanimously
understood. Our aim was to assess the prevalence and effects of obesity on the
cardiometabolic risk factors and systolic function of left ventricle ejection
fraction (LVEF) in patients scheduled for cardiovascular rehabilitation. METHODS:
A cohort of 302 consecutive patients recently treated for ischaemic or valvular
heart disease was matched according to the existence of obesity, defined with
body mass index (BMI >= 30 kg/m(2) ; n = 90 vs. 212), and the advanced grade of
obesity (BMI >= 35 kg/m(2) ; n = 19 vs. 283). Nutritional risk screening was
performed using the standardised NRS-2002 tool. RESULTS: The mean age of patients
was 62.4 +/- 11.2 (range 23-86) years; there were more men than women 244 (80.8%)
: 58 (19.2%). Group of obese conveyed higher prevalence of ischaemic heart
disease than non-obese (OR = 2.69; 95% CI: 1.01-7.20; p = 0.048); while the
difference was insignificant for the advanced grade of obesity (n = 17; 89.5%)
vs. controls (n = 233; 82.3%; p > 0.05). There was no significant difference in
prevalence of other comorbidities (diabetes, glucose intolerance,
hypercholesterolaemia, chronic renal and chronic obstructive pulmonary disease)
between studied groups (p > 0.05). Utilisation of lipid-lowering drugs was of
similar range between the studied groups (p > 0.05), respectively. LVEF (%) was
50.5 +/- 8.2 vs. 50.7 +/- 7.7 (p > 0.05) and 50.6 +/- 7.8 vs. 49.6 +/- 10.9 (p >
0.05; Rho = 0.001; p > 0.05), respectively. CONCLUSION: In studied set of
patients, BMI positively correlated with left ventricle dimension and thickness.
No significant connection of obesity was found with the prevalence of chronic
comorbidities, increased nutritional risk, laboratory diagnostics or systolic
function of left ventricle. Existence of obesity paradox in clinical practice was
in part reaffirmed with our study.
PMID- 24355082
TI - The oral health of heroin drug users: case study in Bosnia and Herzegovina.
AB - BACKGROUND: Injection drug use is a major public health problem. Oral health
problems and the appearance of dental disease among injection drug users (IDUs)
are caused by their lifestyle. The aim of the present study was to examine the
relations between socioeconomic factors, drug use, and oral hygiene habits on the
oral health of heroin drug users. METHODS: A cross-sectional survey on oral
health was carried out as part of UNICEF's research on the biological and
behaviours survey among injection drug users in Sarajevo, Banja Luka and Zenica
in Bosnia and Herzegovina. A sample of 519 IDUs participated in the survey.
Respondent Driven Sampling (RDS) was used to obtain the sample. The data were
obtained through face-to-face interviews using a structured questionnaire related
to socio-demographic characteristics, duration of drug injection, frequency of
drug injection in the last month and oral health. RESULTS: Older participants (OR
= 1.06; 95% CI = 1.02 -1.10), part-time employment (OR = 3.57; 95% CI = 1.02 -
12.20) and unemployment (OR = 3.23; 95% CI = 1.23 - 8.33) in comparison to full
time employment as the referent category, and longer duration of drug injection
(OR = 1.06; 95% CI = 1.003 - 1.12) were predictors of bad oral health. A higher
level of education (OR = 0.56; 95% CI = 0.39 - 0.79), more frequent tooth
brushing (OR = 0.59; 95% CI = 0.49 - 0.71), and regular dental checkups (OR =
3.30; 95% CI = 1.42 - 7.67) were predictors of good oral health. CONCLUSIONS:
Socioeconomic characteristics of IDUs as well as their lifestyles may contribute
to oral health problems. Heroin drug users have specific dental needs, and
programmes to improve their oral health should be an integral part of strategies
to prevent addictions including treatments and harm reduction programmes.
PMID- 24355083
TI - Echocardiographic particle image velocimetry for the evaluation of diastolic
function in hypertrophic nonobstructive cardiomyopathy.
AB - AIMS: To use particle image velocimetry (PIV) echocardiography for the evaluation
of diastolic dysfunction (DD) in patients with hypertrophic nonobstructive
cardiomyopathy (HNCM). METHODS: This study included 50 individuals, thereof 30
patients with DD due to HNCM and 20 healthy individuals who served as controls.
HNCM patients were divided into 3 groups according to DD severity. All subjects
underwent clinical assessment, exercise testing, and standard as well as PIV
echocardiography. RESULTS: Energy dissipation was higher in DD patients than in
the control group. The severity of flow pattern disturbance corresponded to the
degree of DD. In a subgroup of 20 HNCM patients we found significant correlations
between invasive measured left ventricular end-diastolic pressure and noninvasive
PIV parameters for intraventricular pressure differences and filling. Inter
observer variability (mean difference +/- 1.96 SD) for all tested PIV
measurements was good. CONCLUSION: According to DD severity, patients with HNCM
have disturbed intraventricular flow and reduced intraventricular pressure
differences, consistent with a reduced intraventricular suction. PIV
echocardiography appears to be feasible for detailed analysis of ventricular
vortex flow in DD conditions. Further research using PIV echocardiography in
different cardiac pathologies seems warranted.
PMID- 24355084
TI - Valuing narrative in the care of older people: a framework of narrative practice
for older adult residential care settings.
AB - AIMS AND OBJECTIVES: To report on the development of a framework of narrative
practice, in residential care settings for older people. BACKGROUND: Residential
care settings for older people provide care for people who are no longer able to
live in their own home. To date, the impact and structure of nursing practice on
care provision in these settings has proved difficult to conceptualise within a
specific nursing theory framework. DESIGN: A hermeneutic approach incorporating
narrative methods was used. METHODS: Forty-six narrative interviews with older
people in residential care were secondary-analysed for key themes through a three
stage process: by the first author, four focus groups of 12 clinical nurse
managers and two independent experts. Themes were also derived from a focus group
of eight residents who explored person-centredness and narrative. Finally, the
combined findings were used to derive a single set of themes. RESULTS: The
secondary data analysis process led to the development of a framework of
narrative practice for the care of older people in residential settings. The
framework is influenced by narrative enquiry, person-centred practice and
practice development. It has four pillars, prerequisites, care processes, care
environment and narrative aspects of care. To operationalise the framework of
narrative practice, three narrative elements, narrative knowing, narrative being
and narrative doing, need to be considered. Working with the foundational pillars
and the narrative elements would enable staff to 'work in a storied way' and
provide person-centred outcomes and a narrative informed philosophy of care for
older adults in residential care. CONCLUSION: This framework provides nurses with
a template that confirms the identity of the older person taking account of their
biography. RELEVANCE TO CLINICAL PRACTICE: The framework outlines an approach
that provides staff with a template on how to provide person-centred care in a
narrative way.
PMID- 24355085
TI - Fatigue life enhancement of NiTi rotary endodontic instruments by progressive
reciprocating operation.
AB - AIM: To evaluate the effect of reciprocating amplitude and progressive angular
increment on fatigue life enhancement of NiTi rotary endodontic instruments.
METHODOLOGY: ProTaper F2 instruments were operated in steel artificial canals
with both stationary reciprocating (SR) and progressive reciprocating (PR)
motions. The SR motions involved symmetric to and fro reciprocation of +/- 180(o)
, +/- 135(o) , +/- 90(o) , +/- 60(o) and +/- 45(o) . The PR motions were +/-
45(o) stationary motion superimposed with angular increments of 7(o) , 11(o) ,
22.5(o) or 31(o) whenever an instrument completed 1, 10 or 30 reciprocating
cycles (rc). The fatigue lives were compared with those under continuous rotation
(CR) and a reciprocating operation with a forward 144(o) and backward 72(o)
motion proposed by Yared (2008). The statistical significance of these operating
modes on fatigue life was examined using one way anova and post hoc Tukey's tests
at P = 0.05. Fractographic analysis was also applied to probe the fracture
mechanisms of different rotation motions. RESULTS: Fatigue life increased with
decreasing reciprocating amplitude. Operating in the SR increased fatigue life by
355% over that in the CR. Except for the 22.5(o) increment, all PR motions
yielded longer fatigue lives than the SR motion. A progressive reciprocating
operation with a +/- 45(o) reciprocating amplitude and a + 7(o) progressive
angular increment every 10 reciprocating cycles (+/- 45(o) /10rc/+7(o) )
increased fatigue life by 990% over that in the CR motion. In terms of life
enhancement over the CR motion, the larger the curvature the less are the
differences between different movements. Single crack initiation sites were found
in the CR and SR motions, while three crack initiation sites were typical in the
+/- 45(o) /10rc/+7(o) motion. CONCLUSIONS: Fatigue life increased with decreasing
reciprocating amplitude in stationary reciprocation. A progressive reciprocating
operation with +/- 45(o) /10rc/+7(o) motion led to significant fatigue life
enhancement and multiple fatigue crack initiation in NiTi endodontic instruments.
PMID- 24355086
TI - One-pot hydrothermal synthesis of Mn3O4 nanorods grown on Ni foam for high
performance supercapacitor applications.
AB - Mn3O4/Ni foam composites were synthesized by a one-step hydrothermal method in an
aqueous solution containing only Mn(NO3)2 and C6H12N4. It was found that Mn3O4
nanorods with lengths of 2 to 3 MUm and diameters of 100 nm distributed on Ni
foam homogeneously. Detailed reaction time-dependent morphological and component
evolution was studied to understand the growth process of Mn3O4 nanorods. As
cathode material for supercapacitors, Mn3O4 nanorods/composite exhibited superior
supercapacitor performances with high specific capacitance (263 F . g-1 at 1A . g
1), which was more than 10 times higher than that of the Mn3O4/Ni plate. The
enhanced supercapacitor performance was due to the porous architecture of the Ni
foam which provides fast ion and electron transfer, large reaction surface area,
and good conductivity.
PMID- 24355087
TI - Decolorization and COD removal from real textile wastewater by chemical and
electrochemical Fenton processes: a comparative study.
AB - BACKGROUND: Due to the presence of non-biodegradable and toxic compounds, textile
wastewater is difficult to treat by conventional methods. In the present study,
Electrochemical Fenton (EF) and Chemical Fenton (CF) processes were studied and
compared for the treatment of real textile wastewater. The effects of electrical
current, ferrous ion, hydrogen peroxide concentration and reaction time on the
removal efficiencies of COD and color were investigated. All the experiments were
carried out at pH = 3. RESULTS: Both EF and CF processes were mostly efficient
within hydrogen peroxide concentration of 1978 mg/L (H2O2: COD ~ 1.1). The
highest COD and color removal efficiencies were 70.6% and 72.9% respectively
which were obtained through the EF process in 350 mA electrical current, 1978
mg/L hydrogen peroxide and 60 minutes reaction time. Furthermore, the operational
costs of EF and CF processes were 17.56 and 8.6 US$ per kilogram of the removed
COD respectively. CONCLUSION: It was concluded that the electrochemical Fenton
process was more efficient than the chemical Fenton process in the degradation of
textile wastewater. Likewise, Although EF process imposed higher operational
costs than the CF; it dramatically decreased the reaction time to gain the
highest degradation efficiency.
PMID- 24355088
TI - Cooperative binding of LysM domains determines the carbohydrate affinity of a
bacterial endopeptidase protein.
AB - Cellulose, chitin and peptidoglycan are major long-chain carbohydrates in living
organisms, and constitute a substantial fraction of the biomass. Characterization
of the biochemical basis of dynamic changes and degradation of these beta,1-4
linked carbohydrates is therefore important for both functional studies of
biological polymers and biotechnology. Here, we investigated the functional role
of multiplicity of the carbohydrate-binding lysin motif (LysM) domain that is
found in proteins involved in bacterial peptidoglycan synthesis and remodelling.
The Bacillus subtilis peptidoglycan-hydrolysing NlpC/P60 D,L-endopeptidase, cell
wall-lytic enzyme associated with cell separation, possesses four LysM domains.
The contribution of each LysM domain was determined by direct carbohydrate
binding studies in aqueous solution with microscale thermophoresis. We found that
bacterial LysM domains have affinity for N-acetylglucosamine (GlcNac) polymers in
the lower-micromolar range. Moreover, we demonstrated that a single LysM domain
is able to bind carbohydrate ligands, and that LysM domains act additively to
increase the binding affinity. Our study reveals that affinity for GlcNAc
polymers correlates with the chain length of the carbohydrate, and suggests that
binding of long carbohydrates is mediated by LysM domain cooperativity. We also
show that bacterial LysM domains, in contrast to plant LysM domains, do not
discriminate between GlcNAc polymers, and recognize both peptidoglycan fragments
and chitin polymers with similar affinity. Finally, an Ala replacement study
suggested that the carbohydrate-binding site in LysM-containing proteins is
conserved across phyla.
PMID- 24355089
TI - Optimal timing of influenza vaccination in patients with human immunodeficiency
virus: a Markov cohort model based on serial study participant hemoagglutination
inhibition titers.
AB - BACKGROUND: Seasonal influenza vaccination offers one of the best population
level protections against influenza-like illness (ILI). For most people, a single
dose prior to the flu season offers adequate immunogenicity. HIV+ patients,
however, tend to exhibit a shorter period of clinical protection, and therefore
may not retain immunogenicity for the entire season. Building on the work of
Nosyk et al. (2011) that determined a single dose is the optimal dosing strategy
for HIV+ patients, we investigate the optimal time to administer this
vaccination. METHODS: Using data from the "single dose" treatment arm of an RCT
conducted at 12 CIHR Canadian HIV Trials Network sites we estimated semimonthly
clinical seroprotection levels for a cohort (N=93) based on HAI titer levels.
These estimates were combined with CDC attack rate data for the three main
strains of seasonal influenza to estimate instances of ILI over different
vaccination timing strategies. Using bootstrap resampling of the cohort, nine
years of CDC data, and parameter distributions, we developed a Markov cohort
model that included probabilistic sensitivity analysis. Cost, quality adjusted
life-years (QALYs), and net monetary benefits are presented for each timing
strategy. RESULTS: The beginning of December is the optimal time for HIV+
patients to receive the seasonal influenza vaccine. Assuming a willingness-to-pay
threshold of $50,000, the net monetary benefit associated with a Dec 1
vaccination date is $19,501.49 and the annual QALY was 0.833744. INTERPRETATION:
Our results support a policy of administering the seasonal influenza vaccination
for this population in the middle of November or beginning of December, assuming
nothing is know about the upcoming flu season. But because the difference in
between this strategy and the CDC guideline is small-12 deaths averted per year
and a savings of $60 million across the HIV+ population in the US-more research
is needed concerning strategies for subpopulations.
PMID- 24355090
TI - Overcoming barriers to HPV vaccination: non-inferiority of antibody response to
human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs.
a three-dose schedule at 21 months.
AB - For middle and low-income countries, the cost of HPV vaccines remains
challenging. We conducted an open-label nonrandomized clinical trial evaluating
immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a
standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72
and 120 months post-vaccination. Participants were females recruited in Morelos,
Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a
standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule
(currently the girls in the extended schedule had received only the first 2
doses). This report presents the interim analysis results for non-inferiority
between the regimes conducted with the current available data at 21 months after
the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of
non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio
(upper 95% confidence interval [CI]<=2.0) between the standard and the two-dose
schedule in girls at month 21. Immune response to the vaccine was strongest in
adolescent girls and in the 3-dose group. Statistical non-inferiority of the two
dose versus three-dose groups was demonstrated. At 21 months, comparing the
adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55
1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen
was non-inferior when compared to the three-dose response in same-age girls and
with women aged 18-24 years after 21 months of follow-up. The reduction in the
number of doses from the current three-dose schedule may lower overall costs
associated with the vaccination and increase accessibility and compliance with
the recommended dosing of the HPV vaccine.
PMID- 24355092
TI - Endoscopic ultrasound description of liver segmentation and anatomy.
AB - Endoscopic ultrasound (EUS) can demonstrate the detailed anatomy of the liver
from the transgastric and transduodenal routes. Most of the liver segments can be
imaged with EUS, except the right posterior segments. The intrahepatic vascular
landmarks include the major hepatic veins, portal vein radicals, hepatic arterial
branches, and the inferior vena cava, and the venosum and teres ligaments are
other important intrahepatic landmarks. The liver hilum and gallbladder serve as
useful surface landmarks. Deciphering liver segmentation and anatomy by EUS
requires orienting the scan planes with these landmarkstructures, and is
different from the static cross-sectional radiological images. Orientation during
EUS requires appreciation of the numerous scan planes possible in real-time, and
the direction of scanning from the stomach and duodenal bulb. We describe EUS
imaging of the liver with a curved linear probe in a step-by-step approach, with
the relevant anatomical details, potential applications, and pitfalls of this
novel EUS application.
PMID- 24355091
TI - Co-colonization by Haemophilus influenzae with Streptococcus pneumoniae enhances
pneumococcal-specific antibody response in young children.
AB - BACKGROUND: Streptococcus pneumoniae (Spn), Haemophilus influenzae (Hi) and
Moraxella catarrhalis (Mcat) are common bacterial pathogens of respiratory
infections and common commensal microbes in the human nasopharynx (NP). The
effect of interactions among theses bacteria during co-colonization of the NP on
the host immune response has not been evaluated. The objective of this study was
to assess the impact of co-colonization by Hi or Mcat on the systemic antibody
response to vaccine protein candidate antigens of Spn and similarly the impact of
co-colonization by Spn and Mcat on antibody responses to Hi vaccine protein
candidate antigens. METHODS: Serum samples were collected from healthy children
at 6, 9, 15, 18, and 24 months of age when they were colonized with Spn, Hi, Mcat
or their combinations. Quantitative ELISA was used to determine serum IgA and IgG
against three Spn antigens and three Hi antigens, and as well as whole cells of
non-typeable (NT) Spn and Hi. RESULTS: NP colonization by Spn increased serum IgA
and IgG titers against Spn antigens PhtD, PcpA and PlyD and whole cells of NTSpn,
and co-colonization of Hi or Mcat with Spn resulted in further increases of serum
pneumococcal-specific antibody levels. NP colonization by Hi increased serum IgA
and IgG titers against Hi antigens P6, Protein D and OMP26 and whole cells of
NTHi, but co-colonization of Spn or Mcat with Hi did not result in further
increase of serum NTHi-specific antibody levels. CONCLUSION: Co-colonization of
Hi or Mcat with Spn enhances serum antibody response to NTSpn whole cells and Spn
vaccine candidate antigens PhtD, PcPA and PlyD1. Co-colonization appears to
variably modulate pathogen species-specific host adaptive immune response.
PMID- 24355093
TI - "Head to Head": pneumocephalus as a complication of soccer.
AB - BACKGROUND: Pneumocephalus is uncommon in craniofacial trauma and a rare
occurrence in non-contact sports. It may be asymptomatic or present with signs of
increased intracranial pressure and the majority of cases will resolve with
conservative management. However, there should be a high index of clinical
suspicion to recognise, diagnose, and manage it appropriately, as complications
may be fatal. FINDINGS: To our knowledge, this is the first case report of
pneumocephalus secondary to a "minor" head injury during a soccer match.
CONCLUSION: We outline the management of this condition and highlight signs that
should generate a high index of suspicion.
PMID- 24355094
TI - Communication and technology in genetic counseling for familial cancer.
AB - When a cancer predisposing germline mutation is detected in an index case, the
presence of the underlying syndrome is confirmed and the potential for predictive
testing of at-risk relatives is established. However, the reporting of a positive
family history does not routinely lead to communication of information about risk
to close, much less distant relatives. This review summarizes information
technology utilized to address penetration or 'reach' of knowledge of risk within
extended families, including the use of telephone and video counseling to reach
distant patients, and anticipate novel internet-based processes for communication
between investigators and relatives.
PMID- 24355095
TI - Effectiveness of interventions to promote healthy diet in primary care:
systematic review and meta-analysis of randomised controlled trials.
AB - BACKGROUND: A diet rich in fruit, vegetables and dietary fibre and low in fat is
associated with reduced risk of chronic disease. This review aimed to estimate
the effectiveness of interventions to promote healthy diet for primary prevention
among participants attending primary care. METHODS: A systematic review of trials
using individual or cluster randomisation of interventions delivered in primary
care to promote dietary change over 12 months in healthy participants free from
chronic disease or defined high risk states. Outcomes were change in fruit and
vegetable intake, consumption of total fat and fibre and changes in serum
cholesterol concentration. RESULTS: Ten studies were included with 12,414
participants. The design and delivery of interventions were diverse with respect
to grounding in behavioural theory and intervention intensity. A meta-analysis of
three studies showed an increase in fruit consumption of 0.25 (0.01 to 0.49)
servings per day, with an increase in vegetable consumption of 0.25 (0.06 to
0.44) serving per day. A further three studies that reported on fruit and
vegetable consumption together showed a pooled increment of 0.50 (0.13 to 0.87)
servings per day. The pooled effect on consumption of dietary fibre, from four
studies, was estimated to be 1.97 (0.43 to 3.52) gm fibre per day. Data from five
studies showed a mean decrease in total fat intake of 5.2% of total energy (1.5
to 8.8%). Data from three studies showed a mean decrease in serum cholesterol of
0.10 (-0.19 to 0.00) mmol/L. CONCLUSION: Presently-reported interventions to
promote healthy diet for primary prevention in primary care, which illustrate a
diverse range of intervention methods, may yield small beneficial changes in
consumption of fruit, vegetables, fibre and fat over 12 months. The present
results do not exclude the possibility that more effective intervention
strategies might be developed.
PMID- 24355097
TI - A comparison of suit dresses and summer clothes in the terms of thermal comfort.
AB - BACKGROUND: Fanger's PMV equation is the result of the combined quantitative
effects of the air temperature, mean radiant temperature, relative air velocity,
humidity, activity level and clothing insulation. METHODS: This paper contains a
comparison of suit dresses and summer clothes in terms of thermal comfort,
Fanger's PMV equation. Studies were processed in the winter for an office, which
locates in Ankara, Turkey. The office was partitioned to fifty square cells.
Humidity, relative air velocity, air temperature and mean radiant temperature
were measured on the centre points of these cells. Thermal comfort analyses were
processed for suit dressing (Icl = 1 clo) and summer clothing (Icl = 0.5 clo).
RESULTS: Discomfort/comfort in an environment for different clothing types can be
seen in this study. The relationship between indoor thermal comfort distribution
and clothing type was discussed. Graphics about thermal comfort were sketched
according to cells. CONCLUSIONS: Conclusions about the thermal comfort of
occupants were given by PMV graphics.
PMID- 24355096
TI - Estrogen receptors mediate estradiol's effect on sensitization and CPP to cocaine
in female rats: role of contextual cues.
AB - Preclinical studies show that estradiol enhances sensitization to cocaine in
females by mechanisms not fully understood. These studies consistently show that
ovariectomized (OVX) rats exhibit little or no sensitization to cocaine compared
to OVX rats administered estradiol. In this study we varied the dose of cocaine
(10, 15, and 30mg/kg), the length of cocaine treatment (from 5 to 10days) and the
context of cocaine injections to determine if these factors play a role on
estradiol's effects on cocaine sensitization. Because OVX rats are hormonally
compromised, they are not representative of the natural state of the animal, and
thus the physiological context of these studies remains unclear. To address this
issue, we blocked ERs in gonadally intact females by icv administration of the
antiestrogen ICI-182,780. Varying the dose or length of exposure to cocaine does
not alter estradiol's effect on cocaine sensitization. In contrast, a highly
context-dependent sensitization protocol results in robust sensitization even in
OVX rats. Interestingly, using this protocol, sensitization in OVX rats
diminished with time, suggesting that estradiol is necessary for the maintenance
of cocaine sensitization. Blocking brain ERs with ICI completely abolishes the
development and expression of cocaine sensitization in gonadally intact female
rats, even when tested in a highly context-dependent sensitization protocol.
Given these findings, we propose that activation of brain ERs is required for the
development and maintenance of sensitization and CPP.
PMID- 24355098
TI - Benefit of physical fitness against inflammation in obesity: role of beta
adrenergic receptors.
AB - Evidence shows that both poor physical fitness and obesity are linked to low
grade inflammation and inflammatory diseases. However, their relative roles on
inflammation and underlying mechanisms remain unclear. Given the inhibitory
effect of catecholamines on inflammatory cytokine production, we speculated that
compromised responsiveness of immune cells' beta adrenergic receptors (beta-ARs)
to agonists may be associated with constitutively elevated levels of inflammatory
cytokines. We examined circulating levels of inflammatory cytokines TNF, IL
1beta, IL-6 and beta-AR sensitivity of, 70 overweight or obese compared to 26
normal-weight, otherwise healthy individuals in order to investigate the
associations among obesity, physical fitness, and low-grade inflammation and to
examine the role of beta-ARs in these relationships. Cardiorespiratory fitness
was determined by VO2peak (ml/kg/min) via a treadmill exercise. Beta-AR
sensitivity was evaluated by measuring the degree of inhibition in
lipopolysaccharides-stimulated monocytic intracellular TNF production by
isoproterenol. In all participants, BMI, which was initially a predictor of IL
1beta and IL-6 levels independent of demographic characteristics, no longer
significantly predicted them after controlling for fitness levels. Among the
overweight or obese participants, greater cardiorespiratory fitness was a strong
predictor of lower levels of TNF and IL-1beta after controlling for the
covariates. When beta-AR sensitivity was controlled for, however, fitness was no
longer a significant predictor of those cytokines. Monocytic beta-AR sensitivity
was negatively associated with inflammatory marker levels and diminished in obese
individuals; however, when fitness was controlled for, the significant weight
group differences in beta-AR sensitivity disappeared. Our findings indicate that
better cardiorespiratory fitness protects against obesity-related low-grade
inflammation and beta-AR desensitization. Given the significance of beta-AR
function in pathogenesis of various diseases, clinical implications of its role
in the fitness-inflammation association among the obese are profound.
PMID- 24355099
TI - Modification of energy balance induced by the food contaminant T-2 toxin: a
multimodal gut-to-brain connection.
AB - T-2 toxin is one of the most toxic Fusarium-derived trichothecenes found on
cereals and constitutes a widespread contaminant of agricultural commodities as
well as commercial foods. Low doses toxicity is characterized by reduced weight
gain. To date, the mechanisms by which this mycotoxin profoundly modifies feeding
behavior remain poorly understood and more broadly the effects of T-2 toxin on
the central nervous system (CNS) have received limited attention. Through an
extensive characterization of sickness-like behavior induced by T-2 toxin, we
showed that its per os (p.o.) administration affects not only feeding behavior
but also energy expenditure, glycaemia, body temperature and locomotor activity.
Using c-Fos expression mapping, we identified the neuronal structures activated
in response to T-2 toxin and observed that the pattern of neuronal populations
activated by this toxin resembled that induced by inflammatory signals.
Interestingly, part of neuronal pathways activated by the toxin were NUCB
2/nesfatin-1 expressing neurons. Unexpectedly, while T-2 toxin induced a strong
peripheral inflammation, the brain exhibited limited inflammatory response at a
time point when anorexia was ongoing. Unilateral vagotomy partly reduced T-2
toxin-induced brainstem neuronal activation. On the other hand,
intracerebroventricular (icv) T-2 toxin injection resulted in a rapid (<1h)
reduction in food intake. Thus, we hypothesized that T-2 toxin could signal to
the brain through neuronal and/or humoral pathways. The present work provides the
first demonstration that T-2 toxin modifies feeding behavior by interfering with
central neuronal networks devoted to central energy balance. Our results, with a
particular attention to peripheral inflammation, strongly suggest that
inflammatory mediators partake in the T-2 toxin-induced anorexia and other
symptoms. In view of the broad human and breeding animal exposure to T-2 toxin,
this new mechanism may lead to reconsider the impact of the consumption of this
toxin on human health.
PMID- 24355100
TI - DNA testing and molecular screening for colon cancer.
AB - Colon cancer develops and progresses as a consequence of abnormal cellular
molecular changes, many of which result in mutant DNA. Modern molecular
techniques allow examination of individual patient genetic data that ascribe
risk, predict outcome, and/or modify an approach to therapy. DNA testing and
molecular screening are in use today and are becoming a critical and necessary
part of routine patient care. Assessing at-risk patients for hereditary colon
cancer is predicted to move from individual gene testing that is commonly
performed today to whole exome or whole genome sequencing, providing additional
vast information of the patient's genome that might not be related to the colon
cancer syndrome. Detecting mutant DNA from shed tumor cells in fecal material for
colon cancer screening will increase in diagnostic accuracy over time, with
improvements in the panel of mutant DNA being examined and through clinical
testing. DNA mutations and other molecular changes detected directly from within
the colon cancer help to inform and guide the physician for the best approach for
optimal patient care and outcome. The use of epidermal growth factor receptor
targeted therapy in advanced colon cancer patients requires knowledge of the
mutation status for KRAS and BRAF genes, and knowing the mutational status of
PIK3CA may predict how patients respond to aspirin to prevent colon cancer
recurrence. Biologically driven decision-making, or precision medicine, is
becoming increasingly adopted for optimal care and outcome for colon cancer
patients. Gastroenterologists will need to be increasingly aware.
PMID- 24355103
TI - Stakeholders' interest in and challenges to implementing farm-to-school programs,
Douglas County, Nebraska, 2010-2011.
AB - INTRODUCTION: Schools are uniquely positioned to influence the dietary habits of
children, and farm-to-school programs can increase fruit and vegetable
consumption among school-aged children. We assessed the feasibility of, interest
in, and barriers to implementing farm-to-school activities in 7 school districts
in Douglas County, Nebraska. METHODS: We used a preassessment and postassessment
survey to obtain data from 3 stakeholder groups: school food service directors,
local food producers, and food distributors. We had a full-time farm-to-school
coordinator who was able to engage multiple stakeholders and oversee the
development and dissemination of a toolkit. We used descriptive statistics to
make comparisons. RESULTS: Seven food service directors, 5 distributors
identified by the food service directors, and 57 local producers (9 completed
only the preassessment survey, 16 completed only the postassessment survey, and
32 completed both) completed various components of the assessment. Interest in
pursuing farm-to-school activities to incorporate more local foods in the school
lunch program increased during the 2-year project; mean interest in purchasing
local foods by food service directors for their districts increased from 4.4 to
4.7 (on a scale of 1 to 5). CONCLUSION: Implementing farm-to-school programming
in Douglas County, Nebraska, is feasible, although food safety and distribution
is a main concern among food service directors. Additional research on
feasibility, infrastructure, and education is recommended.
PMID- 24355101
TI - Enhanced activity of an angiotensin-(1-7) neuropeptidase in glucocorticoid
induced fetal programming.
AB - We previously identified angiotensin converting enzyme (ACE) and an endopeptidase
activity that degraded angiotensin-(1-7) [Ang-(1-7)] to Ang-(1-5) and Ang-(1-4),
respectively, in the cerebrospinal fluid (CSF) of 6-month old male sheep. The
present study undertook a more comprehensive analysis of the CSF peptidase that
converts Ang-(1-7) to Ang-(1-4) in control and in utero betamethasone-exposed
sheep (BMX). Characterization of the Ang-(1-7) peptidase revealed that the thiol
agents 4-aminophenylmercuric acetate (APMA) and p-chloromercuribenzoic acid
(PCMB), as well as the metallo-chelators o-phenanthroline and EDTA essentially
abolished the enzyme activity. Additional inhibitors for serine, aspartyl, and
cysteine proteases, as well as selective inhibitors against the endopeptidases
neprilysin, neurolysin, prolyl and thimet oligopeptidases did not attenuate
enzymatic activity. Competition studies against the peptidase revealed similar
IC50s for Ang-(1-7) (5MUM) and Ang II (3MUM), but lower values for Ala(1)-Ang-(1
7) and Ang-(2-7) of 1.8 and 2.0MUM, respectively. In contrast, bradykinin
exhibited a 6-fold higher IC50 (32MUM) than Ang-(1-7) while neurotensin was a
poor competitor. Mean arterial pressure (78+/-1 vs. 94+/-2mmHg, N=4-5, P<0.01)
and Ang-(1-7) peptidase activity (14.2+/-1 vs 32+/-1.5fmol/min/ml CSF, N=5,
P<0.01) were higher in the BMX group, and enzyme activity inversely correlated
with Ang-(1-7) content in CSF. Lower Ang-(1-7) expression in brain is linked to
baroreflex impairment in hypertension and aging, thus, increased activity of an
Ang-(1-7) peptidase may contribute to lower CSF Ang-(1-7) levels, elevated blood
pressure and impaired reflex function in this model of fetal programming.
PMID- 24355102
TI - Adaptation changes in dynamic postural control and contingent negative variation
during repeated transient forward translation in the elderly.
AB - BACKGROUND: Adaptation changes in postural control and contingent negative
variation (CNV) for the elderly were investigated during repeated forward floor
translation. METHODS: Fifteen healthy elderly persons, living in the suburban
area of Kanazawa City, Japan, underwent backward postural disturbance by a
forward-floor translation (S2) 2 s after an auditory warning signal (S1). A set
with 20 trials was repeated until a negative peak of late CNV was recognized in
the 600-ms period before S2, and the last set was defined as the final set.
Electroencephalograms, center of foot pressure in the anteroposterior direction
(CoPap), and electromyograms of postural muscles were analyzed. RESULTS: CoPap
displacement generated by the floor translation was significantly decreased until
the twelfth trial in the first set, and mean CoPap displacement was smaller in
the second and final sets than in the first set. The mean displacement was
significantly smaller in the final set than the previous set. A late CNV with a
negative peak was not recognized in the first and second sets. However, most
subjects (13/15) showed a negative peak by the fourth set, when the late CNV
started to increase negatively from about 1,000 ms after S1 and peaked at about
300 ms before S2. At about 160 ms before the CNV peak, the CoPap forward shift
started. The increase in timing of the gastrocnemius activity related to the
CoPap shift was significantly correlated with the CNV peak timing (r = 0.64).
After S2, peak amplitudes of the anterior postural muscles were significantly
decreased in the final set compared to the first set. CONCLUSIONS: It was
demonstrated that even for the elderly, with so many repetitions of postural
disturbance, a late CNV with a negative peak was recognized, leading to accurate
postural preparation. This suggests the improvement of frontal lobe function
(e.g., anticipatory attention and motor preparation) in the elderly.
PMID- 24355104
TI - Clustering of risk factors with smoking habits among adults, Sousse, Tunisia.
AB - INTRODUCTION: In Tunisia, few studies have assessed the association between
tobacco use and other lifestyle risk factors for chronic disease (eg, unhealthy
diet, physical inactivity). We studied 1,880 adults to determine the association
between tobacco use and other lifestyle risk factors in Tunisia. METHODS: This
study was part of an assessment of the prevalence of chronic disease risk factors
in a community-based trial conducted in 2009 to implement a chronic disease
prevention program. The study population was randomly selected from 3 districts
of the region of Sousse. The questionnaires were administered by personal
interview and included the assessment of tobacco use and other chronic disease
risk factors such as unhealthful diet habits and physical inactivity. RESULTS: Of
the 1,880 study participants, 64% were women. The mean age of the participants
was 37.9 (standard deviation, 13.5 y). The prevalence of tobacco use in our
population was 50.4% for men and 3.1% for women. Among men, the proportion of
alcohol consumption was significantly higher among smokers (25.3% vs 5.7% [P
<.001]). Smokers consumed fewer fruits and vegetables and more high-fat, high
salt, and high-sugar foods than did nonsmokers. There was no significant
difference between male smokers and nonsmokers regarding physical activity (P =
.36). CONCLUSION: Physical activity and dietary characteristics may be important
areas for physicians to assess during smoking-cessation interventions.
PMID- 24355105
TI - Overweight, obesity, and perception of body image among slum residents in
Nairobi, Kenya, 2008-2009.
AB - INTRODUCTION: The increase in cardiovascular diseases in sub-Saharan Africa has
been attributed in part to the changes in lifestyle, and the prevalence of risk
factors for cardiovascular disease is higher among urban populations than among
nonurban populations. The objective of this study was to determine the prevalence
of overweight and obesity and examine perceptions of body size differentiated by
sex and other determinants among slum dwellers in Nairobi, Kenya. METHODS:
Analysis included 4,934 adults randomly selected from the Korogocho and Viwandani
slums of Nairobi. Height and weight were measured during interviews; body mass
index (BMI) was calculated. Perceptions of current and ideal body image were
determined by using 18 silhouette drawings of body sizes ranging from very thin
to very obese. We used multivariate logistic regression analysis to determine
predictors of underestimation of body weight among overweight and obese
respondents. RESULTS: Overall, 43.4% of women and 17.3% of men in the study
population were overweight or obese. More than half (53%) of those who were
overweight or obese underestimated their weight; 34.6% of women and 16.9% of men
did so. In all BMI categories, more than one-third of women and men preferred
body sizes classified as overweight or obese. CONCLUSION: This study highlights
the prevalence of overweight and obesity and the strong preference for larger
body size among adults in the slums of Nairobi. Interventions to educate
residents on the health risks associated with excess body weight are necessary as
a part of strategies to reduce the prevalence of risk factors for cardiovascular
disease in these settlements.
PMID- 24355106
TI - Trends in tobacco smoke exposure and blood lead levels among youths and adults in
the United States: the National Health and Nutrition Examination Survey, 1999
2008.
AB - INTRODUCTION: Tobacco smoke is a source of exposure to thousands of toxic
chemicals including lead, a chemical of longstanding public health concern. We
assessed trends in blood lead levels in youths and adults with cotinine-verified
tobacco smoke exposure by using 10 years of data from the National Health and
Nutrition Examination Survey. METHODS: Geometric mean levels of blood lead are
presented for increasing levels of tobacco smoke exposure. Regression models for
lead included age, race/ethnicity, poverty, survey year, sex, age of home, birth
country, and, for adults, alcohol consumption. Lead levels were evaluated for
smokers and nonsmokers on the basis of age of residence and occupation. RESULTS:
Positive trend tests indicate that a linear relationship exists between smoke
exposure and blood lead levels in youths and adults and that secondhand smoke
exposure contributes to blood lead levels above the level caused by smoking.
CONCLUSION: Youths with secondhand smoke exposure had blood lead levels
suggestive of the potential for adverse cognitive outcomes. Despite remediation
efforts in housing and the environment and declining smoking rates and secondhand
smoke exposure in the United States, tobacco smoke continues to be a substantial
source of exposure to lead in vulnerable populations and the population in
general.
PMID- 24355109
TI - Effect of nitrogen, phosphorus and potassium availability on emergence,
nodulation and growth of Trifolium medium L. in alkaline soil.
AB - Little is known about the effects of nutrient availability on the growth of
Trifolium medium in alkaline soil. In 2010, a pot experiment (10 N, P and K
fertiliser treatments) with seeding of T. medium into alkaline soil was performed
and emergence of seedlings, survival, aboveground and belowground organs were
studied. The positive effects of increased nutrient availability on seedling
emergence ranged from 5% in the control to 17% in the high P treatment. The
lowest mortality was in treatments with P and K supply and the highest in
treatments with N supply, due to the sensitivity of young plants to high N
availability. The highest values of most measured aboveground plant traits were
recorded in treatments with simultaneous application of N, P and K. There were
highly positive effects of P supply alone or in combination with N and K on the
development of belowground organs. Taproot length ranged from 11.5 in high N to
40.2 cm in P treatment. There was a negative effect of N application on
nodulation, especially in N treatments, where growth of T. medium was limited by
insufficient P supply. The number of nodules per plant ranged from 0.8 to 4.5 in
the high N and P treatments. As demonstrated in this study, T. medium is a
potentially suitable legume for alkaline soils. It requires a relatively high P
and K supply as well as moderate mineral N supply to achieve its maximum growth
potential.
PMID- 24355110
TI - Harmful metals concentration in sediments and fishes of biologically important
estuary, Bay of Bengal.
AB - Study on the accumulation level of heavy metals was conducted on sediment and
fishes from estuaries of Bay of Bengal. Heavy metals were determined by using
Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) and the
results were compared to permissible limits of WHO/USEPA. The accumulation
patterns of Fe and Cd were found predominantly in all samples tested when
correlated with other metals. It was found that the concentration of metals such
as Cd (3.90 +/- 0.25 MUg/g), Cr (0.44 +/- 0.05 MUg/g), Ni (0.33 +/- 0.01 MUg/g),
and Mn (1.1 +/- 0.11 MUg/g) were exceeding the permissible limit, whereas Fe, Co,
Pb, and Zn were found within the limit of WHO/USEPA at station 1. In station 2,
Cd (16.5 +/- 0.4 MUg/g), Mn (0.67 +/- 0.11 MUg/g), and Cr (0.80 +/- 0.01 MUg/g)
were exceeding the permissible limit, whereas Fe, Co, Pb, Ni, and Zn were found
within the limit. This study emphasizes that Cd and Mn levels in both stations,
are far higher than the acceptable values set by WHO/USEPA and may therefore
present human health hazards. It is therefore mandatory to carry out extensive
research to evaluate the possible environmental risk factors in the vicinity of
both estuaries with respect to heavy metals.
PMID- 24355111
TI - Synthesis and psychobiological evaluation of modafinil analogs in mice.
AB - BACKGROUND AND THE PURPOSE OF THE STUDY: Modafinil, a novel wake-promoting agent
with low potential for abuse and dependence, has a reliable structure to find
some novel derivatives with better activity and lower potential for abuse and
risk of dependency. This study was designed to evaluate psychobiological activity
of some novel N-aryl modafinil derivatives. METHODS: Seven novel N-aryl modafinil
derivatives were synthesized through three reactions: a) preparation of
benzhydrylsulfanyl acetic acid through reaction of benzhydrol with thioglycolic
acid, b) formation of desired amide by adding the substituted aniline to
activated acid with EDC (1-ethyl-3-(3-dimethyl amino propyl) carbodiimide). This
reaction was catalyzed by HOBt (N- hydroxylbenzotriazole), and c) oxidation of
sulfur to sulfoxide group with H2O2. Then, their psychobiological effect on the
performance of male albino mice were compared to that of modafinil as following:
wakefulness by determining the effects of derivatives on phenobarbital-induced
loss of the righting reflex (LOPR); exploratory activity by measuring activity in
the open field test (OFT); depression by measuring immobility time (IT) during
forced swimming test (FST) and the anxiogenic and anxiolytic like effects by
using elevated plus-maze test (EPM). All tests were videotaped and analyzed for
the frequency and duration of the behaviors during the procedures. CONCLUSIONS: 2
(Benzhydrylsulfonyl)-N-(4-chlorophenyl)acetamide (4c) showed comparable result in
LOPR test. However, all analogs were found to be stimulant except 2
(benzhydrylsulfinyl)-N-phenylacetamide (4a). Also 4c led the most exploratory
activity in mice among derivatives. FST results showed that 4a had the longest IT
while modafinil, 2-(benzhydrylsulfinyl)-N-(3-chlorophenyl) acetamide (4b) and 2
(benzhydrylsulfinyl)-N-(4-ethylphenyl) acetamide (4d) had the shortest IT. In
EPM, all derivatives showed anxiogenic-like behavior since they decreased open
arms time and open arms entries and simultaneously increased close arms time.
PMID- 24355112
TI - Left main coronary artery stenosis: a meta-analysis of drug-eluting stents versus
coronary artery bypass grafting.
AB - OBJECTIVES: The goal of this study was to provide a systematic review comparing
the long-term outcomes of percutaneous coronary intervention (PCI) with drug
eluting stents (DES) versus coronary artery bypass graft surgery (CABG) for
unprotected left main coronary artery (UPLM) stenosis. BACKGROUND: One-year
outcomes from randomized controlled trials, observational studies, and pooled
analyses have demonstrated the safety and efficacy of PCI of the UPLM when
compared with CABG. However, there remain concerns over the sustainability of PCI
with DES at longer follow-up. METHODS: Studies published between January 2000 and
December 2012 of PCI versus CABG for UPLM stenosis were identified using an
electronic search and reviewed using meta-analytical techniques. RESULTS: Twenty
four studies comprising 14,203 patients were included in the analysis. There was
no significant difference for all-cause mortality between PCI or CABG at 1 year
(odds ratio [OR]: 0.792, 95% confidence interval [CI]: 0.53 to 1.19), 2 years
(OR: 0.920, 95% CI: 0.67 to 1.26), 3 years (OR: 0.94, 95% CI: 0.60 to 1.48), 4
years (OR: 0.84, 95% CI: 0.53 to 1.33), and 5 years (OR: 0.79, 95% CI: 0.57 to
1.08). The need for target vessel revascularization (TVR) was significantly
higher in patients undergoing PCI at all time points. The occurrence of stroke,
however, was significantly less frequent in patients treated with PCI. The
occurrence of nonfatal myocardial infarction showed a statistically significant
trend towards a lower incidence in CABG patients at 1 year (OR: 1.62, 95% CI:
1.05 to 2.50), 2 years (OR: 1.60, 95% CI: 1.09 to 2.35), and 3 years (OR: 2.06,
95% CI: 1.36 to 3.1). There was no significant difference in combined major
adverse cardiovascular and cerebrovascular events between the 2 groups.
CONCLUSIONS: Our findings suggest that PCI with DES is a safe and durable
alternative to CABG for the revascularization of UPLM stenosis in select patients
at long-term follow-up.
PMID- 24355113
TI - What is the standard of care for patients with left main stenosis?
PMID- 24355114
TI - Long-term clinical outcomes after percutaneous coronary intervention for
ostial/mid-shaft lesions versus distal bifurcation lesions in unprotected left
main coronary artery: the DELTA Registry (drug-eluting stent for left main
coronary artery disease): a multicenter registry evaluating percutaneous coronary
intervention versus coronary artery bypass grafting for left main treatment.
AB - OBJECTIVES: The aim of this study was to compare, in a large all-comer registry,
the long-term clinical outcomes after percutaneous coronary intervention (PCI)
with drug-eluting stents (DES) for ostial/mid-shaft lesions versus distal
bifurcation lesions in unprotected left main coronary artery (ULMCA) stenosis.
BACKGROUND: Limited data are available regarding clinical outcomes following DES
implantation at the different ULMCA sites. METHODS: Patients with ULMCA stenosis
treated by PCI with DES were analyzed in this multinational registry. RESULTS: A
total of 1,612 patients were included: 482 were treated for ostial/mid-shaft
lesions versus 1,130 for distal bifurcation lesions. At a median follow-up period
of 1,250 (interquartile range: 987 to 1,564) days, PCI for distal bifurcation
lesions was associated with a higher incidence of major adverse cardiac events
(propensity-score adjusted hazard ratio [HR]: 1.48, 95% confidence interval [CI]:
1.16 to 1.89; p = 0.001), largely because of the higher target vessel
revascularization rate observed in this group as compared to the ostial/mid-shaft
lesions group (propensity-score adjusted HR: 1.68, 95% CI: 1.19 to 2.38; p =
0.003). These results were sustained following propensity-score matched analysis.
With regard to all-cause death and the composite endpoint of all-cause death and
myocardial infarction, propensity-score adjusted analysis suggested a trend
toward higher rates of these in the distal ULMCA PCI group, although this was not
observed in the propensity-score matched analysis. CONCLUSIONS: This study
demonstrates that PCI for ostial/mid-shaft lesions is associated with better
clinical outcomes than are distal bifurcation lesions in ULMCA, largely because
there is a lower need for repeat revascularization in ostial/mid-shaft lesions.
PMID- 24355115
TI - Impact of 3-dimensional bifurcation angle on 5-year outcome of patients after
percutaneous coronary intervention for left main coronary artery disease: a
substudy of the SYNTAX trial (synergy between percutaneous coronary intervention
with taxus and cardiac surgery).
AB - OBJECTIVES: This study sought to investigate the impact of left main coronary
artery (LMCA) 3-dimensional (3D) bifurcation angle (BA) parameters on 5-year
clinical outcomes of patients randomized to LMCA percutaneous coronary
intervention (PCI) in the SYNTAX (Synergy Between Percutaneous Coronary
Intervention With Taxus and Cardiac Surgery) trial. BACKGROUND: BA can affect
outcome after bifurcation PCI; 3D angiographic analysis provides reliable BA
measurements. METHODS: The diastolic distal BA (between left anterior descending
and left circumflex) and its systolic-diastolic range were explored. A stratified
post-hoc survival analysis was performed for 5-year major adverse cardiac and
cardiovascular events (MACCE) (all-cause death, cerebrovascular accident,
myocardial infarction, or repeat revascularization), a safety endpoint (all-cause
death, cerebrovascular accident, or myocardial infarction), and repeat
revascularization. Analysis was performed in patients where 3D BA was available
pre- and post-PCI. RESULTS: Of 266 patients eligible for analysis, 185 underwent
bifurcation PCI (group B); 1 stent was used in 75 patients (group B1), whereas
>=2 stents were used in 110 patients (group B2). Stratification across pre-PCI
diastolic distal BA tertiles (<82 degrees , 82 degrees to 106 degrees , >=107
degrees ) failed to show any difference in MACCE rates either in the entire study
population (p = 0.99) or in group B patients (p = 0.78). Group B patients with
post-PCI systolic-diastolic range <10 degrees had significantly higher MACCE
rates (50.8% vs. 22.7%, p < 0.001); repeat revascularization and safety endpoint
rates were also higher (37.4% vs. 15.5%, p = 0.002, and 25.4% vs. 14.1%, p=0.055,
respectively). Post-PCI systolic-diastolic range <10 degrees was an independent
predictor of MACCE (hazard ratio: 2.65; 95% confidence interval: 1.55 to 4.52; p
< 0.001) in group B patients. CONCLUSIONS: A restricted post-procedural systolic
diastolic distal BA range resulted in higher 5-year adverse event rates after
LMCA bifurcation PCI. Pre-PCI BA value did not affect the clinical outcome.
PMID- 24355116
TI - Left main percutaneous coronary intervention: growing in maturity.
PMID- 24355117
TI - Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting
stents, and second-generation drug-eluting stents: results from a registry of
18,334 patients.
AB - OBJECTIVES: This study sought to compare the risk of stent thrombosis among
patients treated with bare-metal stents (BMS), first-generation drug-eluting
stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period
of 3 years. BACKGROUND: In patients undergoing coronary stenting, there is a
scarcity of long-term follow-up data on cohorts large enough to compare rates of
stent thrombosis across the stent generations. METHODS: A total of 18,334
patients undergoing successful coronary stent implantation from 1998 to 2011 at 2
centers in Munich, Germany, were included in this study. Patients were stratified
into 3 groups according to treatment with BMS, G1-DES, and G2-DES. RESULTS: The
cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS,
2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared
with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]:
2.05; 95% confidence interval [CI]: 1.47 to 2.86; p < 0.001). G2-DES were
associated with a similar risk of stent thrombosis compared with BMS (OR: 0.82;
95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was
significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to
11.1; p < 0.001), but not with G2-DES compared with BMS (OR: 1.01; 95% CI: 0.32
to 3.25; p = 0.98). CONCLUSIONS: In a large cohort of unselected patients
undergoing coronary stenting, compared with BMS, there was a significant excess
risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of
stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk
of stent thrombosis compared with BMS.
PMID- 24355118
TI - Drug-eluting stents for revascularization of infrapopliteal arteries: updated
meta-analysis of randomized trials.
AB - OBJECTIVES: This study sought to undertake an updated meta-analysis of randomized
trials investigating the outcomes of percutaneous revascularization with primary
drug-eluting stenting in patients with atherosclerotic disease of infrapopliteal
arteries. BACKGROUND: In atherosclerotic disease of infrapopliteal arteries, drug
eluting stents (DESs) improve patency rates compared with plain balloon
angioplasty or bare-metal stents (BMSs). However, the clinical impact of DES
placement in this vascular territory still remains uncertain. METHODS: We
searched MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled
Trials), scientific session abstracts, and relevant Websites. The keywords used
were "below the knee," "infrapopliteal artery," "angioplasty," "drug-eluting
stent(s)," "bare metal stent(s)," "trial," and "randomized trial." Inclusion
criteria were randomized design, intention-to-treat analysis, and a minimum of 6
month follow-up. Exclusion criteria were vessels treated other than
infrapopliteal arteries; devices used other than DESs, plain balloons, or BMSs;
and duplicated data. The primary endpoint was target lesion revascularization;
secondary endpoints were restenosis, amputation, death, and improvement in
Rutherford class. RESULTS: A total of 611 patients from 5 trials were randomly
assigned to DESs (n = 294) versus control therapy (plain balloon angioplasty/BMS
implantation, n = 307). Overall, the median lesion length was 26.8 mm
(interquartile range [IQR]: 18.2 to 30.0 mm) with a reference vessel diameter of
2.86 mm (IQR: 2.68 to 3.00 mm). At a median follow-up of 12 months (IQR: 12 to 36
months), DESs reduced the risk of target lesion revascularization (odds ratio
[OR]: 0.31; 95% confidence interval [CI]: 0.18 to 0.54; p < 0.001), restenosis
(OR: 0.25; 95% CI: 0.15 to 0.43; p < 0.001), and amputation (OR: 0.50; 95% CI:
0.26 to 0.97); p = 0.04) without a significant difference in terms of death (OR:
0.81; 95% CI: 0.45 to 1.49; p = 0.50) and Rutherford class improvement (OR: 1.36;
95% CI: 0.91 to 2.04; p = 0.13) versus control therapy. CONCLUSIONS: In focal
disease of infrapopliteal arteries, DES therapy reduces the risk of
reintervention and amputation compared with plain balloon angioplasty or BMS
implantation without any impact on mortality and Rutherford class at 1-year
follow-up.
PMID- 24355119
TI - Leaving nothing behind.
PMID- 24355121
TI - Where there is smoke, there is fire.
PMID- 24355120
TI - Prevalence and clinical implications of newly revealed, asymptomatic abnormal
ankle-brachial index in patients with significant coronary artery disease.
AB - OBJECTIVES: This study sought to evaluate the association between newly revealed
abnormal ankle-brachial index (ABI) and clinical outcomes in patients with
significant coronary artery stenosis. BACKGROUND: Little is known about the
prevalence and clinical implications of ABI in patients with no claudication or
previous history of peripheral artery disease who undergo diagnostic coronary
angiography. METHODS: Between January 1, 2006, and December 31, 2009, ABI was
evaluated in 2,543 consecutive patients with no clinical history of claudication
or peripheral artery disease who underwent diagnostic coronary angiography.
Abnormal ABI was defined as <=0.9 or >=1.4. The primary endpoint was the
composite of death, myocardial infarction, and stroke over 3 years. RESULTS: Of
the 2,543 patients, 390 (15.3%) had abnormal ABI. Of the 2,424 patients with at
least 1 significant stenosis (>=50%) in a major epicardial coronary artery, 385
(15.9%) had abnormal ABI, including 348 (14.4%) with ABI <=0.9 and 37 (1.5%) with
ABI >=1.4. During a median follow-up of 986 days, the 3-year major adverse event
rate was significantly higher in patients with abnormal than normal ABI (15.7%
vs. 3.3%, p < 0.001). After multivariate analysis, abnormal ABI was identified as
a predictor of primary endpoint (hazard ratio [HR]: 1.87; 95% confidence interval
[CI]: 1.23 to 2.84; p = 0.004). After adjustment by propensity-score matching,
abnormal ABI could predict adverse clinical events in patients with established
coronary artery disease (HR: 2.40; 95% CI: 1.41 to 4.10; p = 0.001). CONCLUSIONS:
The prevalence of newly revealed abnormal, asymptomatic ABI among patients who
have significant CAD on coronary angiography was 15.9%. The presence of abnormal
ABI was associated with a higher incidence of adverse clinical outcomes over 3
years.
PMID- 24355122
TI - Frequency-domain optical coherence tomography assessment of unfavorable kissing
balloon result in unprotected left main intervention.
PMID- 24355123
TI - Optical coherence tomography of a bifurcation lesion treated with bioresorbable
vascular scaffolds with the "mini-crush" technique.
PMID- 24355124
TI - Reply: relationship between myocardial reperfusion, infarct size, and mortality.
PMID- 24355125
TI - Relationship between myocardial reperfusion, infarct size, and mortality.
PMID- 24355126
TI - Back to the future.
PMID- 24355127
TI - A rare cause of acute bowel obstruction in adult.
PMID- 24355128
TI - Morphological characterization of testicular cells, spermatogenesis and formation
of spermatophores in a fish ectoparasite Argulus bengalensis Ramakrishna, 1951
(Crustacea: Branchiura).
AB - The present study has been carried out to describe the cell morphology of the
developing male gametes in a fish ectoparasite, Argulus bengalensis Ramakrishna,
1951. With respect to cell volume and nucleoplasmic index, spermatogonia are the
smallest and primary spermatocytes are the largest in this lineage. The
spermatogonia and the differentiating spermatogenic cells are in separate niches
and confined to different enclaves within each testicular lobe. Spermiogenesis
occurs within the inner enclave of each testicular lobe. During this process the
nucleus becomes streamlined; an acrosome is formed, axoneme is originated, and
residual cytoplasm is discarded through the flagellum. The sperm cell morphology
displays a general pattern comprising head, mid-piece, and a full length
flagellum. In the axoneme 9+2 arrangement of the microtubule is conserved. In
addition to the axoneme, some more singlet microtubules are found surrounding a
fiber sheath and around one of the mitochondria adjacent to the axoneme. This
arrangement indicates a close phylogenetic relationship with pentastomida. In the
present study, structure and formation of spermatophore are described in this
branchiuran parasite.
PMID- 24355129
TI - The identification of AF38469: an orally bioavailable inhibitor of the VPS10P
family sorting receptor Sortilin.
AB - The identification of the novel, selective, orally bioavailable Sortilin
inhibitor AF38469 is described. Structure-activity relationships and syntheses
are reported, along with an X-ray crystal structure of the sortilin-AF38469
protein-inhibitor complex.
PMID- 24355130
TI - Identification of quinones as HER2 inhibitors for the treatment of trastuzumab
resistant breast cancer.
AB - HER2 overexpression is associated with aggressive breast cancer with high
recurrence rate and poor patient prognosis. Treatment of HER2 overexpressing
patients with the HER2 targeting therapy trastuzumab results in acquired
resistance within a year. The HER2/EGFR dual kinase inhibitor lapatinib was shown
to inhibit some trastuzumab resistant breast cancer cell lines and is currently
in clinical trials. Our group has found two new quinone compounds that show
excellent inhibition of breast tumor cells expressing HER2 or the trastuzumab
resistant HER2 oncogenic isoform, HER2Delta16. Compound 4 ((1R,2S,3S)-1,2,3,5,8
pentahydroxy-1,2,3,4-tetrahydroanthracene-9,10-dione) and compound 5 (5,8
dihydroxy-2,3-bis(hydroxymethyl)naphthalene-1,4-dione) showed sub-micromolar
inhibition potency against these cell lines. These compounds also inhibit auto
phosphorylation of the Y1248 and Y1068 residues of HER2 and EGFR, respectively.
PMID- 24355131
TI - Participatory surveillance of diabetes device safety: a social media-based
complement to traditional FDA reporting.
AB - BACKGROUND AND OBJECTIVE: Malfunctions or poor usability of devices measuring
glucose or delivering insulin are reportable to the FDA. Manufacturers submit
99.9% of these reports. We test online social networks as a complementary source
to traditional FDA reporting of device-related adverse events. METHODS:
Participatory surveillance of members of a non-profit online social network,
TuDiabetes.org, from October 2011 to September 2012. Subjects were volunteers
from a group within TuDiabetes, actively engaged online in participatory
surveillance. They used the free TuAnalyze app, a privacy-preserving method to
report detailed clinical information, available through the network. Network
members were polled about finger-stick blood glucose monitors, continuous glucose
monitors, and insulin delivery devices, including insulin pumps and insulin pens.
RESULTS: Of 549 participants, 75 reported device-related adverse events, nearly
half (48.0%) requiring intervention from another person to manage the event. Only
three (4.0%) of these were reported by participants to the FDA. All TuAnalyze
reports contained outcome information compared with 22% of reports to the FDA.
Hypoglycemia and hyperglycemia were experienced by 48.0% and 49.3% of
participants, respectively. DISCUSSION: Members of an online community readily
engaged in participatory surveillance. While polling distributed online
populations does not yield generalizable, denominator-based rates, this approach
can characterize risk within online communities using a bidirectional
communication channel that enables reach-back and intervention. CONCLUSIONS:
Engagement of distributed communities in social networks is a viable
complementary approach to traditional public health surveillance for adverse
events related to medical devices.
PMID- 24355132
TI - A hybrid radioactive and fluorescent tracer for sentinel node biopsy in penile
carcinoma as a potential replacement for blue dye.
AB - BACKGROUND: Sentinel node (SN) biopsy in penile cancer is typically performed
using a combination of radiocolloid and blue dye. Recently, the hybrid
radioactive and fluorescent tracer indocyanine green (ICG)-(99m)Tc-nanocolloid
was developed to combine the beneficial properties of both radio-guidance and
fluorescence imaging. OBJECTIVE: To explore the added value of SN biopsy using
ICG-(99m)Tc-nanocolloid in patients with penile carcinoma. DESIGN, SETTING, AND
PARTICIPANTS: Sixty-five patients with penile squamous cell carcinoma were
prospectively included (January 2011 to December 2012). Preoperative SN mapping
was performed using lymphoscintigraphy and single-proton emission computed
tomography supplemented with computed tomography (SPECT/CT) after peritumoural
injection of ICG-(99m)Tc-nanocolloid. During surgery, SNs were initially
approached using a gamma probe, followed by patent blue dye and/or fluorescence
imaging. A portable gamma camera was used to confirm excision of all SNs.
SURGICAL PROCEDURE: Patients underwent SN biopsy of the cN0 groin and treatment
of the primary tumour. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number
and location of preoperatively identified SNs were documented. Intraoperative SN
identification rates using radio- and/or fluorescence guidance were assessed and
compared with blue dye. Statistical evaluation was performed using a two-sample
test for equality of proportions with continuity correction. RESULTS AND
LIMITATIONS: Preoperative imaging after injection of ICG-(99m)Tc-nanocolloid
enabled SN identification in all patients (a total of 183 SNs dispersed over 119
groins). Intraoperatively, all SNs identified by preoperative SN mapping were
localised using combined radio-, fluorescence-, and blue dye guidance.
Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was
stained by blue dye (p<0.0001). The tissue penetration of the fluorescent signal,
and the rapid flow of blue dye limited the detection sensitivity. A tumour
positive SN was found in seven patients. CONCLUSIONS: ICG-(99m)Tc-nanocolloid
allows for both preoperative SN mapping and combined radio- and fluorescence
guided SN biopsy in penile carcinoma patients and significantly improves optical
SN detection compared with blue dye.
PMID- 24355133
TI - Preparation, characterization and optimization of sildenafil citrate loaded PLGA
nanoparticles by statistical factorial design.
AB - BACKGROUND AND THE AIM OF THE STUDY: The objective of the present study was to
formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co
glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The
relationship between design factors and experimental data was evaluated using
response surface methodology. METHOD: A Box-Behnken design was made considering
the mass ratio of drug to polymer (D/P), the volumetric proportion of the water
to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the
independent agents. PLGA-NPs were successfully prepared and the size (nm),
entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from
NPs post 1 and 8 hrs were assessed as the responses. RESULTS: The NPs were
prepared in a spherical shape and the sizes range of 240 to 316 nm. The
polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied
between 14-62% and 2-6%, respectively. The optimized formulation with a
desirability factor of 0.9 was selected and characterized. This formulation
demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative
drug release of 79% after 12 hrs. In vitro release studies showed a burst release
at the initial stage followed by a sustained release of sildenafil from NPs up to
12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi
model. CONCLUSIONS: Sildenafil citrate NPs with small particle size, lipophilic
feature, high entrapment efficiency and good loading capacity is produced by this
method. Characterization of optimum formulation, provided by an evaluation of
experimental data, showed no significant difference between calculated and
measured data.
PMID- 24355134
TI - Re: efficacy and safety of low dose desmopressin orally disintegrating tablet in
women with nocturia: results of a multicenter, randomized, double-blind, placebo
controlled, parallel group study: P. K. Sand, R. R. Dmochowski, J. Reddy and E.
A. van der Meulen J Urol 2013; 190: 958-964.
PMID- 24355135
TI - Re: re: early detection of prostate cancer: AUA guideline: J. W. Moul, P. C.
Walsh, M. S. Rendell, H. T. Lynch, S. W. Leslie, O. Kosoko-Lasaki, W. P.
Fitzgibbons, I. Powell, A. V. D'Amico and W. J. Catalona J Urol 2013; 190: 1134
1139.
PMID- 24355136
TI - Ultrasensitive electrochemical aptasensor for ochratoxin A based on two-level
cascaded signal amplification strategy.
AB - Ochratoxin A (OTA) has a number of toxic effects to both humans and animals, so
developing sensitive detection method is of great importance. Herein, we describe
an ultrasensitive electrochemical aptasensor for OTA based on the two-level
cascaded signal amplification strategy with methylene blue (MB) as a redox
indicator. In this method, capture DNA, aptamers, and reporter DNA functionalized
gold nanoparticles (GNPs) were immobilized on the electrode accordingly, where
GNPs were used as the first-level signal enhancer. To receive the more sensitive
response, a larger number of guanine (G)-rich DNA was bound to the GNPs' surface
to provide abundant anchoring sites for MB to achieve the second-level signal
amplification. By employing this novel strategy, an ~8.5 (+/-0.3) fold
amplification in signal intensity was obtained. Afterward, OTA was added to force
partial GNPs/G-rich DNA to release from the sensing interface and thus decreased
the electrochemical response. An effective sensing range from 2.5pM to 2.5nM was
received with an extremely low detection limit of 0.75 (+/-0.12) pM. This
amplification strategy has the potential to be the main technology for aptamer
based electrochemical biosensor in a variety of fields.
PMID- 24355137
TI - The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5
HTTVNTR gene polymorphisms and borderline personality disorder in female heroin
dependent Chinese subjects.
AB - OBJECTIVE: To explore the association between the 5-HTR2A-1438A/G, COMTVal158Met,
MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with co-morbid borderline
personality disorder (BPD) in female heroin-dependent patients. SUBJECTS AND
METHODS: In a case control study, we compared the polymorphic distributions of 5
HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 296 female
heroin-dependent patients (including 61 patients with BPD and 235 without BPD)
and 101 normal females by genotypes, alleles, and interaction between genes.
RESULTS: Female heroin-dependent subjects with BPD have lower frequency of the
high activity allele (L: 4 repeats (4R)) of MAOA-LPR than those female heroin
dependent subjects without BPD, and have higher 5-HTTVNTR 10R/10R genotype
frequency than normal female controls, with adjusted P-value<0.05 (after adjusted
for multiple testing by 1000-fold permutation tests) respectively. By MDR
(Multifactor Dimensionality Reduction) analyses, the interactive effects between
MAOA-LPR and 5-HTTVNTR, and among MAOA-LPR, 5-HTTVNTR and rs6311 were close to
the significance level (P=0.05) in predicting the risk of co-morbidity of BPD and
heroin dependence relative to normal female controls, with 1000-fold permutation
testing P-value<0.06 however >0.05 respectively. CONCLUSION: 5-HTTVNTR and MAOA
LPR may have independent predictive effects on co-morbid BPD in female heroin
dependent patients; the gene-gene interactions between MAOA-LPR and 5-HTTVNTR,
and among MAOA-LPR, 5-HTTVNTR and rs6311 might also be involved in the etiology
of this co-morbidity.
PMID- 24355138
TI - Extending the clinical benefit of endocrine therapy for women with hormone
receptor-positive metastatic breast cancer: differentiating mechanisms of action.
AB - Principal goals of therapy for women with hormone receptor (HR)-positive
metastatic breast cancer (MBC) are to maintain a good quality of life and to
prolong survival; another important goal is to delay initiation of chemotherapy.
Most women with tumors that are estrogen receptor (ER)-positive, progesterone
receptor (PR)-positive, or both are treated initially with endocrine therapy
because of its effectiveness and relatively low toxicity. Several classes of
single-agent endocrine therapies are available for postmenopausal women,
including the nonsteroidal aromatase inhibitors (AIs), steroidal AIs, selective
ER modulators, selective ER downregulators, progestins, androgens, and high-dose
estrogen. In addition, combination therapy, either with 2 different endocrine
agents or with endocrine therapy plus newer targeted therapies, provides some
relatively new strategies for the treatment of these patients. Nevertheless,
disease resistance ultimately develops with each endocrine regimen, and many
questions remain regarding the optimal timing and sequencing of these treatments.
This article reviews the efficacy and safety of endocrine therapy regimens in
women with HR-positive MBC, and it addresses the effect of prior endocrine
therapies and the mechanisms of action of the different endocrine regimens within
the context of overall treatment goals.
PMID- 24355139
TI - [Complications of peripheral parenteral nutrition. Clinical observations of 2
cases].
AB - INTRODUCTION: Peripheral parenteral nutrition (PPN) is artificial nutrition used
when digestive absorption is insufficient. It supplies the nutritional needs of
the patient and permits administration through a peripheral catheter. WE PRESENT
2 CLINICAL CASES: The first one entails an epidermolisis through extravasation
masked by temporo-spatial disorientation of the patient with appearance of
flictenes (blisters). Prolonged treatment and consultation with plastic surgery
were required. The second case entails a chemical phlebitis with early detection
by nursing professionals. It was resolved with short term treatment and did not
require consultation with the plastic surgeon. PLANNING CARE: We elaborated a
care plan aimed at identifying real or potential problems related with possible
complications of intravenous PPN administration, such as phlebitis and
extravasation. The aim of this research was prevention, early detection and
treatment. DISCUSSION: Phlebitis is related with catheter characteristics, in
dwelling time and high osmolarity of PPN. Early action decreases injury of the
affected tissue. In case 1, the patient requires 19 days of curing. This was only
72 h in case 2. CONCLUSION: The nursing staff plays an essential role in catheter
election, localization, administration and preventing complications. Staff
training and a procedure protocol greatly reduce the incidence of phlebitis,
avoid discomfort for the patient and reduce health care cost.
PMID- 24355140
TI - Short and long-term antinutritional effect of the trypsin inhibitor ApTI for
biological control of sugarcane borer.
AB - Plant-derived trypsin inhibitors have been shown to have potent anti-insect
effects and are a promising alternative for the biological control of pests. In
this work, we tested the anti-insect activity of Adenanthera pavonina trypsin
inhibitor (ApTI) against Diatraea saccharalis larvae, a major insect pest in
sugarcane. The addition of 0.1% ApTI in short-term assays resulted in 87% and 63%
decreased trypsin and chymotrypsin activities respectively. ApTI was not digested
after 60h incubation with D. saccharalis midgut proteases. The chronic effects of
ApTI on F0 and F1 generations of D. saccharalis were also analyzed. The larvae
from the F0 generation showed 55% and 21% decreased larval and pupal viability,
respectively. ApTI-fed larvae from the F1 generation showed a decrease of 33% in
survival rate and 23% in the average larval weight. Moreover, ApTI treatment
reduced trypsin and chymotrypsin activities in F1 larvae. Thus, the anti-insect
effects of ApTI on consecutive generations (F0 and F1) of D. saccharalis larvae
demonstrate its potential for long-term control of this pest.
PMID- 24355141
TI - Bilateral persistent sciatic artery diagnosed by multidetector-row CT
angiography.
PMID- 24355142
TI - Endovascular biopsy: evaluating the feasibility of harvesting endothelial cells
using detachable coils.
AB - The absence of safe and reliable methods to harvest vascular tissue in situ
limits the discovery of the underlying genetic and pathophysiological mechanisms
of many vascular disorders such as aneurysms. We investigated the feasibility and
comparable efficacy of endothelial cell collection using a spectrum of
endovascular coils. Nine detachable coils ranging in k coefficient (0.15-0.24),
diameter (4.0 mm-16.0 mm), and length (8.0 cm-47.0 cm) were tested in pigs. All
coils were deployed and retrieved within the iliac artery of pigs (three
coils/pig). Collected coils were evaluated under light microscopy. The total and
endothelial cells collected by each coil were quantified. The nucleated cells
were identified by Wright-Giemsa and DAPI stains. Endothelial and smooth muscle
cells were identified by CD31 and alpha-smooth muscle actin antibody staining.
Coils were deployed and retrieved without technical difficulty. Light microscopy
demonstrated sheets of cellular material concentrated within the coil winds. All
coils collected cellular material while five of nine (55.6%) coils retrieved
endothelial cells. Coils collected mean endothelial cell counts of 89.0+/-101.6.
Regression analysis demonstrated a positive correlation between increasing coil
diameter and endothelial cell counts (R(2)=0.52, p = 0.029). Conventional
detachable coils can be used to harvest endothelial cells. The number of
endothelial cells collected by a coil positively correlated with its diameter.
Given the widespread use of coils and their well-described safety profile their
potential as an endovascular biopsy device would expand the availability of
tissue for cellular and molecular analysis.
PMID- 24355143
TI - Feasibility study of perfusion imaging using flat detector CT with an intra
arterial injection protocol compared to conventional multi-slice perfusion CT
with an intravenous injection protocol.
AB - This study investigated the feasibility of using intra-arterial injection-based
cerebral blood volume (CBV) imaging with flat detector computed tomography (CT,
IAFD-CBV). It is proven that this new method could provide comparable physiologic
information as standard intravenous injection-based multi-slice computed
tomography CBV imaging (IVCT-CBV). Twelve patients were examined using both IAFD
CBV and IVCT-CBV. An experienced neuroradiologist read both sets of generated CBV
maps. If a physiologic perfusion disorder was detected in standard IVCT-CBV, the
focus was to check whether IAFD-CBV indicated the same disorder or not.
Otherwise, if no disorder was detected, relative CBV (rCBV) values at different
basal ganglia regions were measured for both CBV maps and then compared. For
three patients with lesions, IAFD-CBV and IVCT-CBV showed similar perfusion
disorders in the corresponding regions. For nine patients without lesions, both
CBV maps showed good symmetry of contrast agent (CA) distribution for left/right
hemisphere, the total average of rCBV was found to be 0.94 -/+0.18 and 1.01
/+0.14 (1.0 for perfect symmetry) in IAFD-CBV and IVCT-CBV, respectively.
However, compared to IVCT-CBV, IAFD-CBV imaging required 70% less contrast agent
(CA). In general, a good correlation between IAFD-CBV and IVCT-CBV was found for
all 12 patients. Minor deviations of IAFD-CBV were only detected at regions
supplied by the middle cerebral artery. IAFD-CBV imaging, which can be directly
performed in a catheterization laboratory, was proven to be technically feasible
for real-time CBV assessment of the whole brain with good accuracy, and minimized
CA usage.
PMID- 24355144
TI - Evaluation of the Solitaire system in a canine arterial thromboembolic occlusion
model: is it safe for the endothelium?
AB - The Solitaire system has recently been increasingly used for acute stroke
treatment in which the endothelial safety immediately after its use has not been
evaluated. This study was performed to evaluate the endothelial status when using
a Solitaire system in a canine arterial occlusion model. Thromboembolic occlusion
of both internal maxillary arteries was achieved in five mongrel dogs. In each
animal, the Solitaire system (ev3, Irvine, CA, USA) was used for primary
thrombectomy on the right side and for temporary stenting on the left side.
Efficacy was assessed by comparing the recanalization rates, and safety was
assessed using angiographic and microscopic assessments. Endothelial injuries
were evaluated with light microscopy (LM) and scanning electron microscopy (SEM).
Successful revascularizations were observed following primary thrombectomy in all
five animals (100%) and after temporary stenting in two (40%). There was no
incidence of vasospasm or vessel perforation in either group. Distal migration of
the clot occurred in two animals that underwent primary thrombectomy. Endothelial
injury was seen after primary thrombectomy in two animals (40%) and after
temporary stenting in one (20%). The lesions presented as defects of the internal
elastic lamina on LM and denudation of the wavy endothelial surface on SEM.
During mechanical thrombectomy, the Solitaire system can cause endothelial injury
both in primary thrombectomy and temporary stenting. Primary thrombectomy is
likely to have a higher recanalization rate with increased endothelial injury.
PMID- 24355145
TI - Vertebral artery position in the setting of cervical degenerative disease:
implications for selective cervical transforaminal epidural injections.
AB - Cervical transforaminal epidural injections (C-TfEI) are commonly performed in
patients with cervical radiculopathy/pain. C-TfEIs are typically performed
without incident but adverse events can occur. Using CT-fluoroscopy-guided C
TfEI, we commonly observe the vertebral artery in proximity to the target
injection site. The purpose of this study was to assess the position of the
vertebral artery relative to the typical C-TfEI injection point. CT-fluoroscopy
guided C-TfEIs were performed at 70 levels in 68 patients with radiculopathy/neck
pain (age range 19-83 yrs, mean 50.6 yrs). Degenerative neural foraminal
narrowing at each level was characterized (normal-to-mild, moderate, severe).
Vertebral artery position was categorized as: anterior (normal), partially
covering neural foramen, complete/near-complete covering the neural foramen.
Additional measured variables included angle of needle trajectory, foraminal
angle, and whether or not needle trajectory intersected with the vertebral
artery. Foraminal vertebral artery covering correlated with severity of foraminal
degenerative narrowing (p=0.003). Complete/near-complete covering was seen in:
65% severely narrowed foramina, 30% moderately narrowed foramina and 10%
normal/mildly-narrowed foramina. Needle trajectory intersected with the vertebral
artery in 30 of 70 injections (46%) by CT-fluoroscopy, frequently associated with
shallow (lateral) approaches. Foraminal angle, approximating oblique fluoroscopic
technique, suggests needle trajectory intersection with the vertebral artery in
27 of 70 foramina (39%). Vertebral artery position is commonly displaced into the
foramen in patients with advanced cervical degenerative disease. Operator
awareness of altered vertebral artery position is important for determination of
optimal needle trajectory and tip placement prior to injection in patients
undergoing C-TfEI.
PMID- 24355146
TI - In vitro reproduction of device deformation leading to thrombotic complications
and failure of flow diversion.
AB - Flow diverters (FDs) are increasingly used for complex intracranial aneurysms. As
these self-expanding devices are deployed across an aneurysm neck, they can
undergo deformations. The potential clinical consequences of FD deformations
remain unclear. We describe an immediate thrombotic complication attributed to a
stereotypical stenotic deformation of an FD extremity that can occur when landing
zones are of insufficient length. This case is supplemented with in vitro studies
showing the relationship between i) the length of the landing zones and ii)
discrepancies between the diameter of the device and recipient vessel, and the
severity of FD stenosis. In vitro, a shorter landing zone was associated with a
progressive stenotic deformation of the terminal ends of all FDs studied. This
deformation was more pronounced when the diameter of the device was oversized
compared to the size of the recipient tube. In our clinical case, the presence of
this deformation led to an immediate thrombotic complication, requiring
deployment of a second stent to correct the observed stenosis. In addition,
treatment failure ultimately led to a fatal rupture, a failure that can be
explained by residual flows through a more porous transition zone, another
characteristic FD deformation which occurs when they are oversized as compared to
the parent vessel, but free to expand at the level of the aneurysm. Proper
selection of device diameter and length of the landing zone is important, and may
decrease the incidence of deformation-related complications.
PMID- 24355147
TI - Susceptibility-weighted imaging in carotido-cavernous fistulas. A case control
study.
AB - This study determined the utility and accuracy of susceptibility-weighted MRI
(SWI) for the detection of carotid cavernous fistulas. We retrospectively
compared SWI images in nine patients (Group 1, case group) of DSA-proved carotid
cavernous fistula (CCF) and 19 DSA negative cases for CCF as a control group
(Group 2). Group 1 was again sub-grouped into direct and indirect types. Using
uniform region-of-interest measurements, signal intensity within the superior
ophthalmic vein (SOV) and the superior sagittal sinus (SSS) were measured on
magnitude images of SWI. The SOV/SSS signal intensity ratio was calculated in
each case and the mean values of the two groups were compared. Eleven SOV/SSS
signal intensity ratios in Group 1 (7 unilateral and two bilateral CCF), 38 in
Group 2 (both sides in 19 control subjects) were included. Median +/-
interquartile range of SOV/SSS ratios for Group 1, Group 2, indirect and direct
type CCFs were 1.07 +/- 0.43, 0.39 +/- 0.23, 0.83 +/-0.29, 1.4 +/-0.38
respectively. Mann-Whitney test between Groups 1 and 2 was statistically
significant with P<0.0001. All cases and controls were reliably distinguished
with SOV/SSS signal intensity ratio of 0.64 as cut-off. Direct CCF cases had
consistently higher ratios than indirect CCF. SWI was highly sensitive for
detection and differentiation of both direct and indirect CCF. Only one case of
corticovenous reflux was missed by SWI. SWI is useful for detection of CCF and to
differentiate between direct and indirect CCF.
PMID- 24355148
TI - Endovascular treatment of traumatic carotid cavernous fistula with balloon
assisted sinus coiling. A technical description and initial results.
AB - This study aimed to propose an alternative treatment for carotid cavernous
fistula (CCF) using the balloon-assisted sinus coiling (BASC) technique and to
describe this procedure in detail. Under general anesthesia, we performed the
BASC procedure to treat five patients with traumatic CCF. Percutaneous access was
obtained via the right femoral artery, and a 7F sheath was inserted, or
alternatively, a bifemoral 6F approach was accomplished. A microcatheter was
inserted into the cavernous sinus over a 0.014-inch microwire through the
fistulous point; the microcatheter was placed distal from the fistula point, and
a "U-turn" maneuver was performed. Through the same carotid access, a compliant
balloon was advanced to cross the point of the fistula and cover the whole
carotid tear. Large coils were inserted using the microcatheter in the cavernous
sinus. Coils filled the adjacent cavernous sinus, respecting the balloon.
Immediate complete angiographic resolution was achieved, and an early
angiographic control (mean = 2.6 months) indicated complete stability without
recanalization. The clinical follow-up has been uneventful without any recurrence
(mean = 15.2 months). An endovascular approach is optimal for direct CCF. Because
the detachable balloon has been withdrawn from the market, covered stenting
requires antiplatelet therapy and its patency is unconfirmed, but cavernous sinus
coiling remains an excellent treatment option. Currently, there is no detailed
description of the BASC procedure. We provide detailed angiograms with suitable
descriptions of the exact fistula point, and venous drainage pathways.
Familiarity with these devices makes this technique effective, easy and safe.
PMID- 24355149
TI - Y-crossing of braided stents with stents and flow diverters does not cause
significant stenosis in bench-top studies.
AB - Y-stent placement to treat bifurcation aneurysms requires the second device to
cross the confines of the first stent, with concerns regarding the formation of
stenosis of the second device at the site of crossing. Various braided stents and
flow diverters (FDs) were deployed to cross through a high porosity braided
stent, in a Y configuration, with the ends of the devices inserted in plastic
tubes of various diameters, leaving the mid-portion free to expand. The ensuing
constructs were photographed, paying attention to the degree of stenosis, if any,
created where the second device crosses the first stent. Experiments were
repeated selecting different zones of the first stent as the site of crossing for
the second device, different tube diameters, and changing the angle of the
bifurcation. Crossing the first stent did not cause the second stent to become
significantly stenosed in any case. Crossing through the transition or expansion
zone of the first device had no influence on results. Different bifurcation
angles had no influence on the occurrence of stenosis. Y-stent placement to treat
arterial bifurcations using braided self-expanding stents and FDs does not lead
to significant stenosis in bench-top studies.
PMID- 24355150
TI - Fenestrations of the basilar artery demonstrated on magnetic resonance
angiograms: an analysis of 212 cases.
AB - Fenestration of the basilar artery (BA) is a rare variant of the intracranial
artery, well demonstrated in autopsy and angiographic studies. Some angiographic
series show a high incidence of associated aneurysms at the basilar fenestration
site. The purpose of this study is to report the incidence of BA fenestration,
its configurations, associated aneurysms, and arterial anomalies in a large
series of intracranial MR angiograms (MRAs). A total of 16,416 MRAs were
retrospectively reviewed to identify the location, size and associated
intracranial arterial anomalies of BA fenestrations. All images were obtained
with the time-of-flight (TOF) technique. Of the 16,416 MRAs, 215 fenestrations
were found in 212 cases (1.29%). Most fenestrations were located in the proximal
BA. The average length of the fenestration was 4.6 mm; the largest was 15.6 mm.
No aneurysm was found at the site of the fenestration. Thirteen aneurysms were
found in nine cases at locations other than the BA: seven in the middle cerebral
artery (MCA), one in the anterior cerebral artery (ACA), one in the anterior
communicating artery (Acom), one in the vertebral artery (VA), one at the carotid
siphon, and two at the internal carotid-posterior communicating artery (IC-PC).
Arterial anomalies in other locations were found in 26 cases. BA fenestrations
were found in 1.29% of the 16,416 cases studied. There were no aneurysms at the
BA fenestration site. Aneurysms at the BA fenestration site may be an exceedingly
rare phenomenon.
PMID- 24355151
TI - Onyx embolization of an intracranial hemangiopericytoma by direct transcranial
puncture.
AB - Intracranial hemangiopericytomas are uncommon but highly vascular dural-based
tumors which commonly derive arterial blood supply from both intracranial and
extracranial circulations. Microsurgical resection of these lesions may result in
excessive blood loss without the aid of pre-operative embolization. We describe a
case of a large tentorial hemangiopericytoma for which initial resection was
aborted due to excessive blood loss. After failed endovascular access, we
performed a direct transcranial puncture of the hemangiopericytoma through the
craniotomy defect and successfully embolized the tumor with Onyx. Post
embolization gross total resection was achieved with a limited amount of
operative blood loss. Direct puncture embolization provides several advantages
over traditional endovascular embolization including decreased procedural
duration, circumventing challenging arterial anatomy, and a lower risk of stroke
in the presence of extracranial-to-intracranial anastamoses. While direct
puncture embolization has been described for tumors of the neck and skull base,
this is the first reported case of an intracranial hemangiopericytoma
successfully devascularized by direct transcranial puncture Onyx embolization.
PMID- 24355152
TI - Endovascular exclusion of the anterior communicating artery with flow-diverter
stents as an emergency treatment for blister-like intracranial aneurysms. A case
report.
AB - Blood blister-like aneurysms (BLAs) are rare lesions, associated with diffuse
subarachnoid hemorrhage (SAH). BLAs tend to rebleed quickly after first bleeding
and must be treated as an emergency. Acute treatment is challenging using
surgical and endovascular approaches due to the fragile aneurysm wall and small
sac. Flow-diverter stents (FDSs) may offer a new option for the treatment of
difficult small aneurysms. We describe a case of a ruptured BLA on the anterior
communicating artery (AComA) treated in the acute phase of SAH by endovascular
exclusion of the AComA with deployment of two FDSs in the A1/A2 junctions of both
anterior cerebral arteries (ACAs). A 61-year-old man was admitted for diffuse SAH
with a focal interhemispheric hematoma. Angiography revealed multiple arterial
wall irregularities on the AComA and both ACAs. We performed an endovascular
shunt of the AComA by deploying two FDSs in both A1/A2 junctions. Immediate
control injections confirmed flow diversion in the A1/A2 segments of the ACAs
with decreased blood flow in the AComA. The patient's course in hospital was
uneventful. A three-month follow-up angiogram confirmed complete exclusion of the
aneurysms, complete exclusion of the AComA, and patency of the two ACAs without
any persistent arterial wall irregularity. Endovascular bypass using an FDS for a
ruptured BLA has never been described. It establishes a new therapeutic option
despite the need for antiplatelet therapy. Endovascular AComA exclusion using an
FDS may be a solution when no other treatment is available for a ruptured BLA.
PMID- 24355153
TI - Stent placement to treat ruptured vertebral dissecting aneurysms.
AB - Conventional endovascular treatment may have limitations for vertebral dissecting
aneurysm involving the origin of the posterior inferior cerebellar artery (PICA).
We report our experiences of treating vertebral dissecting aneurysm with PICA
origin involvement by placing a stent from the distal vertebral artery (VA) to
the PICA to save the patency of the PICA. Stenting from the distal VA to the PICA
was attempted to treat ruptured VA dissecting aneurysm involving the PICA origin
with sufficient contralateral VA in eight patients. The procedure was
successfully performed in seven patients with one failure because of PICA origin
stenosis, which was treated with two overlapping stents. In the seven patients,
PICAs had good patency on postoperative angiography and transient lateral
brainstem ischemia represents a procedure-related complication. Follow-up
angiographies were performed in seven patients and showed recanalization of the
distal VA in three patients without evidence of aneurysmal filling. There was no
evidence of aneurysm rupture during the follow-up period, and eight patients had
favorable outcomes (mRS, 0 - 1). Placing a stent from the distal VA to the PICA
with VA occlusion may present an alternative to conventional endovascular
treatment for vertebral dissecting aneurysm with PICA origin involvement with
sufficient contralateral VA.
PMID- 24355155
TI - Variability in evolution and course of gunshot injuries to the neck and impact on
management. A case report.
AB - This study reports the differences in evolution and course of multiple
pseudoaneurysms (PAs) and an axillary arteriovenous fistula (AVF) after
penetrating vascular trauma due to shotgun injury to the head and neck. We
describe the unusual case of a young man who, following penetrating shotgun
injuries to the head and neck, developed multiple PAs of the common carotid,
vertebral and superficial temporal arteries as well as an axillary AVF. Serial
angiographic follow-up studies documented differences in time of occurrence,
evolution and course of these lesions. This allowed for tailored management using
endovascular (AVF, superficial temporal artery PAs) and conservative (carotid and
vertebral PAs) treatment. No complication occurred and complete cure of all
lesions was achieved and documented after seven months. Time of occurrence,
evolution and regression of penetrating vascular injuries can differ
significantly even in the same patient. Close angiographic follow-up helps not
only detect a lesion with delayed occurrence, but also provides a practical basis
for decision-making for optimal therapeutic management.
PMID- 24355154
TI - Bilateral cervical spinal dural arteriovenous fistulas with intracranial venous
drainage mimicking a foramen magnum dural arteriovenous fistula.
AB - We describe a unique case of bilateral cervical spinal dural arteriovenous
fistulas mimicking an intracranial dural arteriovenous fistula near the foramen
magnum. We review its detection via MRI and digital subtraction angiography and
subsequent management through surgical intervention. Pitfalls in diagnostic
angiography are discussed with reference to accurate location of the fistula
site. The venous anastomotic connections of the posterior midline spinal vein to
the medial posterior medullary vein, posterior fossa bridging veins, and dural
venous sinuses of the skull base are discussed with reference to problem-solving
in this complex case. The mechanism of myelopathy through venous hypertension
produced by spinal dural fistulas is also emphasized.
PMID- 24355156
TI - Pseudomeningocele after traumatic nerve root avulsion. A novel technique to close
the fistula.
AB - Traumatic brachial plexus complete avulsions and the subsequent formation of
pseudomeningoceles are a well-known entity that usually remains asymptomatic.
Pseudomeningocele is due to the dural sleeve encasing the damaged roots and the
spinal liquid that may accumulate locally or in the supraclavicular soft tissues.
The pseudomeningocele, added to the associated lesion of the plexus and usually
the surrounding vessels, may become difficult to manage. We describe the novel
management of a traumatic pseudomeningocele using an endovascular technique.
PMID- 24355157
TI - Spinal cord infarction is an unusual complication of intracranial
neuroendovascular intervention.
AB - Spinal cord infarction is an unusual complication of intracranial
neuroendovascular intervention. The authors report on two cases involving spinal
cord infarction after endovascular coil embolization for large basilar-tip
aneurysms. Each aneurysm was sufficiently embolized by the stent/balloon
combination-assisted technique or double catheter technique. However,
postoperatively, patients presented neurological symptoms without cranial nerve
manifestation. MRI revealed multiple infarctions at the cervical spinal cord. In
both cases, larger-sized guiding catheters were used for an adjunctive technique.
Therefore, guiding catheters had been wedged in the vertebral artery (VA). The
wedge of the VA and flow restriction may have caused thromboemboli and/or
hemodynamic insufficiency of the spinal branches from the VA (radiculomedullary
artery), resulting in spinal cord infarction. Spinal cord infarction should be
taken into consideration as a complication of endovascular intervention for
lesions of the posterior circulation.
PMID- 24355160
TI - Editorial: "Interventional Neuroradiology: a Neuroscience sub-specialty?".
AB - Interventional Neuroradiology (INR) is not bound by the classical limits of a
speciality, and is not restricted by standard formats of teaching and education.
Open and naturally linked towards neurosciences, INR has become a unique source
of novel ideas for research, development and progress allowing new and improved
approaches to challenging pathologies resulting in better anatomo-clinical
results. Opening INR to Neurosciences is the best way to keep it alive and
growing. Anchored in Neuroradiology, at the crossroad of neurosciences, INR will
further participate to progress and innovation as it has often been in the past.
PMID- 24355158
TI - Endovascular therapy in hyperacute ischaemic stroke: history and current status.
AB - This is a literature review on to the use of endovascular therapy in hyperacute
ischaemic stroke secondary to large vessel occlusion (LVO). The prognosis for LVO
is generally poor and the efficacy of intravenous tissue plasminogen activator
(IV TPA) in the treatment of this subtype of stroke is questionable. It is well
documented that recanalisation is associated with improved outcomes but IV TPA
has limited efficacy in LVO recanalisation and the complication rates are higher
for IV TPA in this stroke subset. Improved recanalisation rates have been
demonstrated with intra-arterial TPA and first and second generation mechanical
techniques but the rate of favourable outcome has not overtly mirrored this
improvement. Several controversial trials using these early techniques have
recently been published but fail to reflect modern practice which centres on the
use of stent-retriever technology. This has been proven to be superior to older
techniques. Not only are recanalisation rates higher, but the speed of
recanalisation is greater and clinical results are improved. Multiple
observational studies demonstrate consistently high rates of LVO recanalisation;
TICI 2b/3 in the order of 65-95% and, rates of favourable outcome (mRS 0-2) in
the order of 55% (42.5-77%) in clinically moderate to severe stroke with
complicating symptomatic haemorrhage in the order of 1.5-15%. A major factor
determining outcome is time to treatment but success has been demonstrated using
these devices with bridging therapy, after IV TPA failure or as a stand-alone
treatment.
PMID- 24355161
TI - The vascular surgeon's experience with adrenal venous sampling for the diagnosis
of primary hyperaldosteronism.
AB - BACKGROUND: Adrenal venous sampling (AVS) is used to distinguish between
bilateral idiopathic hyperplasia and a functional adrenal tumor in patients with
hyperaldosteronism. Successful sampling from both adrenal veins is necessary for
lateralization and may require more than 1 procedure. AVS has traditionally been
performed by interventional radiologists; however, our goal was to examine the
outcomes when performed by a vascular surgeon. METHODS: All patients with a
diagnosis of hyperaldosteronism were referred for AVS regardless of imaging
findings. Cortisol and aldosterone levels were measured in blood samples from
both adrenal veins. Postoperative analysis of intraoperative laboratory values
before and after cosyntropin administration determined successful cannulation and
sampling of each vein. RESULTS: Between 2007 and 2012, 53 patients underwent AVS
by one vascular surgeon. The average age was 54 and 63% were men. Our success
rate increased with experience, because during the earlier years (2007-2010)
primary and secondary success rates were 58% and 68%, respectively compared with
later years (2011-2012) when primary and secondary success rates were 82% and
95%, respectively (P<0.05). Results of AVS altered localization of disease
compared with what had been anticipated based on preoperative imaging and thus
influenced surgical decision making in 47% of cases. CONCLUSIONS: AVS is an
important procedure in the work up of hyperaldosteronism to help identify and
localize metabolically active tumors. It is an additional area in medicine where
a vascular surgeon can lend expertise. Success with the procedure improves with
experience and should be performed by high volume surgeons.
PMID- 24355162
TI - Household task participation of children and adolescents with cerebral palsy,
Down syndrome and typical development.
AB - This cross-sectional study compared patterns of household task participation
(e.g., performance, assistance and independence) of youth with cerebral palsy
(CP), Down syndrome (DS) and typical development (TD). Parents of 75 children and
adolescents were interviewed to report on their youths' active engagement in
daily self-care and family-care tasks, using the children helping out:
responsibilities, expectations and supports (CHORES) questionnaire. Groups were
equivalent in age (mean=9.3 years; SD=2.2 years), sex (male=39; female=36),
respondent education, presence of maid, and number of siblings at home, but
differed on child cognitive function and family socioeconomic status, with the DS
and the CP groups scoring lower than the TD group but not different from each
other. ANOVA revealed group differences on CHORES performance of self-care tasks
(p=0.004), on total participation score (p=0.04) and on assistance scores
(p<0.02). Post hoc comparisons showed that TD group scored higher than CP and DS
groups on performance and assistance in self-care tasks and total assistance; TD
and CP groups were similar on total performance and assistance in family-care
tasks. The groups also differed on independence indices; the TD index was greater
than the CP and DS, and the CP index was greater than the DS. Parents from the
three groups did not differ on ratings of importance regarding their children's
household participation (p=0.416). In spite of observed differences, children and
adolescents with CP and DS are actively engaged in daily self-care and family
care tasks; their participation at home is not prevented by the presence of their
disabilities.
PMID- 24355164
TI - The molecular properties of nitrobenzanthrone isomers and their mutagenic
activities.
AB - The mutagenic activity of five mono-substituted nitrobenzanthrones (NBA) has been
determined in the Ames assay (Takamura-Enya et al., 2006). In the present study,
a theoretical investigation of the electronic properties of all mono-substituted
NBA isomers and their relation to mutagenic activity are presented. Equilibrium
geometries, vertical ionization potentials (VIP), vertical electron affinities
(VEA), relative energies, dipole moments and electronic dipole polarizabilities,
and the IR and Raman spectra of NBA isomers calculated by Density Functional
Theory (DFT) methods are presented. The position of the nitro group affects the
spectral features of the IR and Raman spectra of the NBA isomers. The results
show that a good linear relationship exists between the summation of Raman
activities (?ARaman) over all the 3N-6 vibrational modes and the mutagenic
activity of the NBA isomers in Salmonella typhimurium strains. The spectroscopic
results suggest that the unknown mutagenic activities of 4-NBA, 5-NBA, 6-NBA, 8
NBA and 10-NBA are predicted to follow the order 4-NBA>10-NBA>5-NBA>8-NBA>6-NBA.
PMID- 24355163
TI - Theranostic tumor homing nanocarriers for the treatment of lung cancer.
AB - The drugs/strategies to selectively inhibit tumor blood supply have generated
interest in recent years for enhancement of cancer therapeutics. The objective of
this study was to formulate tumor homing PEGylated CREKA peptide conjugated
theranostic nanoparticles of DIM-C-pPhC6H5 (DIM-P) and investigate in vivo
antitumor activity as well as evaluate the targeted efficiency to lung tumors
using imaging techniques. DIM-P loaded Nanoparticles (NCs-D) were prepared using
lipids, and DOGS-NTA-Ni and the surface of NCs-D were modified with PEGylated
CREKA peptide (PCNCs-D). PCNCs-D showed 3 fold higher binding to clotted plasma
proteins in tumor vasculature compared to NCs-D. PCNCs-D showed 26%+/-4% and
22%+/-5% increase in tumor reduction compared to NCs-D in metastatic and
orthotopic models respectively. In-vivo imaging studies showed ~40 folds higher
migration of PCNCs-Di in tumor vasculature than NCs-Di. Our studies demonstrate
the role of PCNCs-D as theranostic tumor homing drug delivery and imaging systems
for lung cancer diagnosis and treatment. FROM THE CLINICAL EDITOR: This study
demonstrates a very efficient delivery system to address lung cancer growth
through blood supply inhibition.
PMID- 24355165
TI - A yeast bioassay for direct measurement of thyroid hormone disrupting effects in
water without sample extraction, concentration, or sterilization.
AB - The present study introduces an improved yeast bioassay for rapid yet sensitive
evaluation of thyroid hormone disruption at the level of thyroid receptor (TR) in
environmental water samples. This assay does not require water sample preparation
and thus requires very little hands-on time. Based on different beta
galactosidase substrates, two modified bioassays, a colorimetric bioassay and a
chemiluminescent bioassay, were developed. The compounds tested included the
known thyroid hormone 3,3',5-triiodo-l-thyronine (T3), the specific TR antagonist
amiodarone hydrochloride (AH) and phthalate esters (PAEs), which potentially
disrupt thyroid hormone signaling. The EC50 values for T3 were similar to those
previously obtained using a 96-well plate bioassay. TR antagonism by AH was
studied in the presence of 2.5 * 10(-7)M T3, and the concentration producing 20%
of the maximum effect (RIC20) for AH was 3.1 * 10(-7)M and 7.8 * 10(-9)M for the
colorimetric bioassay and chemiluminescent bioassay, respectively. None of the
tested PAEs induced beta-galactosidase expression, but diethylhexyl phthalate,
benzyl butyl phthalate and dibutyl phthalate demonstrated TR antagonism.
Furthermore, water samples collected from Guanting reservoir in Beijing were
evaluated. Although TR agonism was not observed, antagonism was detected in all
water samples and is expressed as AH equivalents. The toxicology equivalent
quantity values obtained by the chemiluminescent bioassay ranged from 21.2 +/-
1.6 to 313.9 +/- 28.8 MUg L(-1) AH, and similar values were obtained for the
colorimetric bioassay. The present study shows that the modified yeast bioassay
can be used as a valuable tool for quantification of thyroid hormone disrupting
effects in environmental water samples.
PMID- 24355166
TI - Pharmaceutical supply chain risks: a systematic review.
AB - INTRODUCTION: Supply of medicine as a strategic product in any health system is a
top priority. Pharmaceutical companies, a major player of the drug supply chain,
are subject to many risks. These risks disrupt the supply of medicine in many
ways such as their quantity and quality and their delivery to the right place and
customers and at the right time. Therefore risk identification in the supply
process of pharmaceutical companies and mitigate them is highly recommended.
OBJECTIVE: In this study it is attempted to investigate pharmaceutical supply
chain risks with perspective of manufacturing companies. METHODS: Scopus, PubMed,
Web of Science bibliographic databases and Google scholar scientific search
engines were searched for pharmaceutical supply chain risk management studies
with 6 different groups of keywords. All results found by keywords were reviewed
and none-relevant articles were excluded by outcome of interests and researcher
boundaries of study within 4 steps and through a systematic method. RESULTS: Nine
articles were included in the systematic review and totally 50 main risks based
on study outcome of interest extracted which classified in 7 categories. Most of
reported risks were related to supply and supplier issues. Organization and
strategy issues, financial, logistic, political, market and regulatory issues
were in next level of importance. CONCLUSION: It was shown that the majority of
risks in pharmaceutical supply chain were internal risks due to processes, people
and functions mismanagement which could be managed by suitable mitigation
strategies.
PMID- 24355167
TI - The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced
bladder calculus in mice.
AB - Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine
induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was
investigated. One experiment, comprising untreated, melamine and recovery groups,
was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed
normal-diet in untreated or a melamine-diet in other groups. The melamine-diet
was then substituted with normal-diet in recovery group. Both of BC and BEH were
observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at
the same melamine-diet durations. The BEH was diffuse with many mitotic figures,
4-7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked
differences in BEH degree were observed in the two different melamine-diet
durations. On 4-42 days after melamine withdrawal, BC was not found, as the
progressive regression with complete regression of BEH was observed, along with
well-defined ageing/apoptotic cells in the superficial regions of BEH regression
tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self
limiting in rows of nuclei, and can return to normal. Melamine withdrawal
duration is critical for the BEH regression. Tissue of the BEH and its regression
is ideal for exploring the renewal as well as growth biology of mammalian
urothelium.
PMID- 24355168
TI - Deoxynivalenol induced oxidative stress and genotoxicity in human peripheral
blood lymphocytes.
AB - Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study
consists in using diverse cellular and molecular assays to evaluate cytotoxicity,
genotoxicity as well as oxidative damage and to investigate their mechanisms in
human peripheral blood lymphocytes. The human lymphocytes were cultured in eight
different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6,
12 and 24 h. DON was able to decrease cell viability and cause damage to the
membrane, the chromosomes or the DNA at all times of culture. It was also able to
induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24
h. The results of the RT-PCR and the Western Blot indicated that DON is able to
enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to
inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human
lymphocytes. This mechanism is probably related to depletion of antioxidase and
oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting
the ability of DNA repair.
PMID- 24355169
TI - Transesterification of a series of 12 parabens by liver and small-intestinal
microsomes of rats and humans.
AB - Hydrolytic transformation of parabens (4-hydroxybenzoic acid esters; used as
antibacterial agents) to 4-hydroxybenzoic acid and alcohols by tissue microsomes
is well-known both in vitro and in vivo. Here, we investigated
transesterification reactions of parabens catalyzed by rat and human microsomes,
using a series of 12 parabens with C1-C12 alcohol side chains.
Transesterification of parabens by rat liver and small-intestinal microsomes
occurred in the presence of alcohols in the microsomal incubation mixture. Among
the 12 parabens, propylparaben was most effectively transesterified by rat liver
microsomes with methanol or ethanol, followed by butylparaben. Relatively low
activity was observed with longer-side-chain parabens. In contrast, small
intestinal microsomes exhibited higher activity towards moderately long side
chain parabens, and showed the highest activity toward octylparaben. When
parabens were incubated with liver or small-intestinal microsomes in the presence
of C1-C12 alcohols, ethanol and decanol were most effectively transferred to
parabens by rat liver microsomes and small-intestinal microsomes, respectively.
Human liver and small-intestinal microsomes also exhibited significant
transesterification activities with different substrate specificities, like rat
microsomes. Carboxylesterase isoforms, CES1b and CES1c, and CES2, exhibited
significant transesterification activity toward parabens, and showed similar
substrate specificity to human liver and small-intestinal microsomes,
respectively.
PMID- 24355170
TI - The safety of beta-carotene from Yarrowia lipolytica.
AB - Crystalline beta-carotene from genetically modified Yarrowia lipolytica is an
alternative source of beta-carotene for use as a nutritional supplement. To
support the use of beta-carotene from Y. lipolytica as a food ingredient, the
genotoxic and subchronic toxicity potential of this compound was determined.
Genotoxicity was examined using Salmonella typhimurium and Escherichia coli (Ames
test), a chromosomal aberration assay in Chinese Hamster Ovary WBL cells, and the
micronucleus test in CD-1 mice. All three assays showed no significant results
due to beta-carotene from Y. lipolytica. In a subchronic toxicity study in SD
rats, beta-carotene from Y. lipolytica was administered by oral gavage for
13weeks at 0, 125, 250 or 500mg/kg per day. Adverse effects were not observed
following clinical, clinical pathology and gross- and histopathological
evaluations of dosed rats; thus, the no-observed-adverse effect level (NOAEL) for
beta-carotene from Y. lipolytica was 500mg/kg, the highest dose used in the
study. In conclusion, beta-carotene derived from Y. lipolytica was shown in
genotoxicity models and a standard rat subchronic rat study to have a safety
profile similar to that of the current commercial products (synthetic and
natural) with no unexpected finding attributable to the alternative source.
PMID- 24355172
TI - How to form alliances with families and communities: the provision of informal
supports to families keeps kids safe.
PMID- 24355171
TI - Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE
activation: Akt and AMPKalpha as upstream targets.
AB - Thymoquinone (TQ), an active constituent of Nigella sativa, possesses anti
inflammatory and anticancer properties. Multiple lines of evidence suggest that
the induction of heme oxygenase-1 (HO-1) suppresses inflammation and
carcinogenesis. In the present study, we examined the effect of TQ on HO-1
expression in human keratinocytes (HaCaT) and elucidated its underlying molecular
mechanisms. TQ induced the expression of HO-1 in HaCaT cells in a concentration-
and time-dependent manner. Treatment with TQ increased the localization of
nuclear factor (NF)-erythroid2-(E2)-related factor-2 (Nrf2) in the nucleus and
elevated the antioxidant response element (ARE)-reporter gene activity. Knockdown
of Nrf2 abrogated TQ-induced HO-1 expression and the ARE luciferase activity. TQ
induced the phosphorylation of extracellular signal-regulated kinase (ERK), Akt
and cyclic AMP-activated protein kinase-alpha (AMPKalpha). Pharmacological
inhibition of Akt or AMPKalpha, but not that of ERK, abrogated TQ-induced nuclear
localization of Nrf2, the ARE-luciferase activity and the expression of HO-1. TQ
also generated reactive oxygen species (ROS) and pretreatment with N-acetyl
cysteine (NAC) abrogated TQ-induced ROS accumulation, Akt and AMPKalpha
activation, Nrf2 nuclear localization, the ARE-luciferase activity, and HO-1
expression in HaCaT cells. Taken together, TQ induces HO-1 expression in HaCaT
cells by activating Nrf2 through ROS-mediated phosphorylation of Akt and
AMPKalpha.
PMID- 24355173
TI - Traditional and alternative metrics: the full story of impact.
PMID- 24355174
TI - The signaling pathway for aldosterone-induced mitochondrial production of
superoxide anion in the myocardium.
AB - Mineralocorticoid receptor (MR) antagonists decrease morbidity and mortality in
heart failure patients for whom oxidative stress is usual; however, the
underlying mechanism for this protection is unclear. Since aldosterone stimulates
reactive oxygen species (ROS) production in several tissues, we explored its
effect and the intracellular pathway involved in the rat myocardium. Aldosterone
dose-dependently increased O2(-) production in myocardial slices. At 10 nmol/L,
aldosterone increased O2(-) to 165 +/- 8.8% of control, an effect prevented not
only by the MR antagonists eplerenone and spironolactone (107 +/- 7.8 and 103 +/-
5.3%, respectively) but also by AG1478 (105 +/- 8.0%), antagonist of the EGF
receptor (EGFR). Similar results were obtained by silencing MR expression through
the direct intramyocardial injection of a lentivirus coding for a siRNA against
the MR. The aldosterone effect on O2(-) production was mimicked by the mKATP
channel opener diazoxide and blocked by preventing its opening with 5-HD and
glibenclamide, implicating the mitochondria as the source of O2(-). Inhibiting
the respiratory chain with rotenone or mitochondrial permeability transition
(MPT) with cyclosporine A or bongkrekic acid also canceled aldosterone-induced
O2(-) production. In addition, aldosterone effect depended on NADPH oxidase and
phosphoinositide 3-kinase activation, as apocynin and wortmannin, respectively,
inhibited it. EGF (0.1 MUg/mL) similarly increased O2(-), although in this case
MR antagonists had no effect, suggesting that EGFR transactivation occurred
downstream from MR activation. Inhibition of mKATP channels, the respiratory
chain, or MPT did not prevent Akt phosphorylation, supporting that it happened
upstream of the mitochondria. Importantly, cardiomyocytes were confirmed as a
source of aldosterone induced mitochondrial ROS production in experiments
performed in isolated cardiac myocytes. These results allow us to speculate that
the beneficial effects of MR antagonists in heart failure may be related to a
decrease in oxidative stress.
PMID- 24355175
TI - [Adding value to the care at the final stage of chronic diseases].
AB - There is a growing number of people with advanced chronic health conditions and
with palliative care needs who die without their health and social needs
satisfied. This is enough to redefine the traditional models of care in order to
focus on the person, rather than on the disease. In these new models, the
important role of nursing is unquestionably to promote an approach based on
comprehensive care, coordination and continuity, and at a social health level
appropriate to respond to the care of patients who require complex long-term
care. The nurse contribution in the end stages of chronic conditions must be in
the value of care. Taking care of someone is to be concerned about them. And this
is related to attitude, commitment and responsibility. In the care of patients
who live in a situation of extreme vulnerability, it is possible to help them
feel warmth, confident, relieve their suffering, respect their autonomy, and help
them them find sense and hope, through daily tasks. With gestures, words and
facial expressions that go with this care, it is possible to preserve patient
dignity.
PMID- 24355177
TI - How to offer precious "gifts" to young investigators and increase self
satisfaction.
PMID- 24355176
TI - Eye-specific gene expression following embryonic ethanol exposure in zebrafish:
roles for heat shock factor 1.
AB - The mechanisms through which ethanol exposure results in developmental defects
remain unclear. We used the zebrafish model to elucidate eye-specific mechanisms
that underlie ethanol-mediated microphthalmia (reduced eye size), through time
series microarray analysis of gene expression within eyes of embryos exposed to
1.5% ethanol. 62 genes were differentially expressed (DE) in ethanol-treated as
compared to control eyes sampled during retinal neurogenesis (24-48 h post
fertilization). The EDGE (extraction of differential gene expression) algorithm
identified >3000 genes DE over developmental time in ethanol-exposed eyes as
compared to controls. The DE lists included several genes indicating a mis
regulated cellular stress response due to ethanol exposure. Combined treatment
with sub-threshold levels of ethanol and a morpholino targeting heat shock factor
1 mRNA resulted in microphthalmia, suggesting convergent molecular pathways.
Thermal preconditioning partially prevented ethanol-mediated microphthalmia while
maintaining Hsf-1 expression. These data suggest roles for reduced Hsf-1 in
mediating microphthalmic effects of embryonic ethanol exposure.
PMID- 24355178
TI - CT brain findings in a patient with elevated brain cesium levels.
AB - We describe the CT findings in the brain of a woman with pathologically proven
elevated levels of blood and tissue cesium. The 42-year-old woman had been
receiving cesium chloride as a non-mainstream treatment for metastatic breast
carcinoma. She presented to hospital following a seizure, and died 48 hours after
admission. A brain CT performed on hospital admission showed a diffuse increase
in attenuation of brain parenchyma. Autopsy revealed elevated levels of cesium in
blood and solid organs including the brain. We hypothesize that the imaging
findings are attributable to the abnormally elevated level of brain cesium at the
time of the CT scan. To our knowledge, this is the first reported case of this
imaging finding.
PMID- 24355180
TI - Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic
perivascular disease process to blame?
AB - CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement
responsive to steroids) is a recently described chronic inflammatory disorder
involving the brainstem with characteristic imaging findings. Since it was
originally described in 2002, only a handful of cases have been reported in the
literature. We describe two additional cases of CLIPPERS with characteristic
clinical and radiological findings. Besides the previously described MR findings,
one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a
finding which has not been previously reported. We hypothesize that the lacunar
infarcts are caused by this chronic infiltrative perivascular disease process.
PMID- 24355181
TI - Subdural B cell lymphoma. Imaging features, histopathology. Literature review.
AB - Dural-based B cell lymphomas are rare and have a female preponderance. A 60-year
old Asian man with a history of trivial trauma presented with generalised tonic
clonic seizures and headache. Imaging and clinical work-up was done. A
temporoparietal subdural lesion with no evidence of systemic lymphoma was
detected. Intraoperatively, a dural-based mass lesion was seen with thickened
dura and biopsy-proven B cell lymphoma, and the patient was then kept on
chemotherapy. A suspicion of this rare entity should be considered in imaging of
dural-based lesions.
PMID- 24355182
TI - Primary gliosarcoma of the brain: radiologic and histopathologic features.
AB - Gliosarcoma is a rare central nervous system (CNS) neoplasm with biphasic glial
and non-glial malignant components. Here we describe the radiologic and
histopathologic features observed in five cases of primary gliosarcoma. The mean
age at diagnosis in the studied patients was 54.2 years; these patients were
predominantly males (male:female ratio = 4:1). At diagnosis all patients had
several clinical deterioration. The most common symptoms of presentation were:
headache (5/5 cases), seizures (4/5 cases) and hemiparesis (1/5 cases). All the
tumors were large (mean major diameter= 4.12+/-1.64 cm) at diagnosis as evidenced
in computer tomography (CT) scans and magnetic resonance images (MRIs), with
preferential involvement of the temporal lobe and frequent associated deviation
of the midline structures. Other common characteristics identified on CT scans
and MRIs were partial contrast medium uptake with annular pattern (5/5 cases),
peripheral edema (5/5 cases), and central calcification (3/5 cases). In
additional a peak of dye uptake was observed (4/5 cases) on MRI spectrometry. In
the histopathology, the glial component showed malignant astrocytes, with high
Ki67 (>60%) and p53 positivity; the sarcomatous components displayed pleomorphic
spindle cells similarly with p53 positivity and high Ki67 (75-90%) in all cases.
Dedifferentiation to pleomorphic sarcoma (two cases), fibrosarcoma (one case),
leiomyosarcoma (one case) and MPNST (one case) were documented. All patients
received radiotherapy/chemotherapy and had a median overall survival of ten
months. The study of radiologic and histopathologic features in primary
gliosarcomas of the brain is a priority to achieve early diagnosis that can be
translated to better outcomes. Here we describe the radiologic and
histopathologic features observed in a group of gliosarcoma patients with
variable histopathologic dedifferentiation.
PMID- 24355179
TI - Brain ischemia in patients with intracranial hemorrhage: pathophysiological
reasoning for aggressive diagnostic management.
AB - Patients with intracranial hemorrhage have to be managed aggressively to avoid or
minimize secondary brain damage due to ischemia, which contributes to high
morbidity and mortality. The risk of brain ischemia, however, is not the same in
every patient. The risk of complications associated with an aggressive
prophylactic therapy in patients with a low risk of brain ischemia can outweigh
the benefits of therapy. Accurate and timely identification of patients at
highest risk is a diagnostic challenge. Despite the availability of many
diagnostic tools, stroke is common in this population, mostly because the
pathogenesis of stroke is frequently multifactorial whereas diagnosticians tend
to focus on one or two risk factors. The pathophysiological mechanisms of brain
ischemia in patients with intracranial hemorrhage are not yet fully elucidated
and there are several important areas of ongoing research. Therefore, this review
describes physiological and pathophysiological aspects associated with the
development of brain ischemia such as the mechanism of oxygen and carbon dioxide
effects on the cerebrovascular system, neurovascular coupling and respiratory and
cardiovascular factors influencing cerebral hemodynamics. Consequently, we review
investigations of cerebral blood flow disturbances relevant to various
hemodynamic states associated with high intracranial pressure, cerebral embolism,
and cerebral vasospasm along with current treatment options.
PMID- 24355183
TI - Desmoplastic infantile ganglioglioma with late presentation. A clinical,
radiological and histopathological analysis.
AB - Desmoplastic infantile ganglioglioma (DIG) is a rare supratentorial tumor in the
central nervous system. Definitive diagnosis of this neoplasm is based on
histopathologic analysis evaluating distinctive findings such as the fibroblastic
differentiation. Here we present a clinical case of DIG with a long follow-up in
an eight-year-old boy with a six-month history of recurrent emesis, psychomotor
hyperactivity and generalized tonic-clonic seizures. Computed tomography scan and
magnetic resonance imaging (MRI) showed a cystic, heterogeneous, mass on the
right temporal uncus. A histopathological diagnosis of late presentation DIG was
made. We documented the immunohistochemical expression of a molecular soft tissue
/ muscle differentiation marker (h-CaD) in addition to a low proliferative index
(Ki-67) in this case. After surgical intervention, a control MRI showed changes
of right frontal-temporal craniotomy and a persistent mass in the anterior and
medial temporal lobe with basal extension. Further surgical intervention was
performed, completely removing the tumor, which had the same characteristics. The
patient is asymptomatic while receiving anticonvulsant therapy (phenytoin) with
no evidence of tumor recurrence on MRI after a follow-up of five years. The low
grade and soft tissue appearance in images are correlated with the
histopathologic and immunohistochemical profile of this tumor, but the rarity of
this tumor makes a presumptive diagnosis by images a challenge. The above
mentioned molecular markers or new ones could be used as molecular targets for
molecular imaging studies to increase the probability of a pre-operative
diagnosis based on molecular features through images.
PMID- 24355184
TI - Lhermitte-Duclos disease. A case report.
AB - Lhermitte-Duclos disease is a rare pathologic condition consisting of a
dysplastic gangliocytoma of the cerebellum. Its association with phacomatosis and
an autosomal dominant neoplastic syndrome, Cowden's syndrome is also known.
Modern neuroimaging contributes to a correct diagnosis and pre- and postoperative
evaluation. Here we describe the morphologic and metabolic aspects of the disease
as shown by conventional MRI, diffusion imaging and spectroscopy in a 31-year-old
woman. In addition, the specific neuroradiologic characteristics are presented
and discussed in the light of the main pathologic and clinical features, such as
hypertrophy of the cerebellar folia associated with white matter atrophy.
PMID- 24355185
TI - Arteriovenous malformation in the brain: a theoretical study explaining the
behavior of liquid embolic agents during endovascular treatment.
AB - There is no theoretical study on blood flow in brain arteriovenous malformation
(AVM). We present a numerical theory on AVM and liquid embolic agent AVM
embolization. Darcy's law was used to compute flow relations for brain AVMs.
Maag's formula was used to explain the diffuse patterns of N-butyl-2
cyanoacrylate (NBCA) and ethylene-vinyl alcohol copolymer (EVOH) in brain AVMs.
According to Darcy's law, the instantaneous blood flow rate through an AVM is
directly proportional to the pressure drop between two places in the AVM and
indirectly proportional to the distance between them. The greater the pressure
gradient (through the AVM), the greater the discharge rate, and the discharge
rate of blood will often differ through different AVM (or even through the same
AVM, in a different direction) even if the same pressure gradient exists in both
cases. Subsequent to Darcy's initial discovery, Maag found that the radius of
NBCA or EVOH diffusion is inversely proportional to their viscosity. Darcy's Law
and Maag's formula could be used to analyze flow patterns of brain AVM and liquid
embolic agent behavior in AVM near ideal.
PMID- 24355186
TI - Treatment of wide-neck basilar tip aneurysms using the Web II device.
AB - Endovascular treatment has assumed a major role in the management of intracranial
aneurysms. Although current techniques have proven extremely effective in the
embolization of a large number of intracranial aneurysms, wide-necked basilar tip
aneurysms represent a subset that continues to pose technical challenges in
treatment. This study reports our experience with WEB II, a new embolization
device employed in four patients with this type of aneurysm.
PMID- 24355187
TI - Preoperative embolization of carotid chemodectoma: a technical challenge that can
be customized according to angioarchitecture. Illustrative cases.
AB - Preoperative embolization of carotid paraganglioma is increasingly used to reduce
the risk of surgical bleeding obtaining a more precise and extensive tumor
resection. Currently the technique can be customized in consideration of the
different tumor angioarchitecture, thanks to embolic materials with different
vascular penetration: solid particles of polyvinyl-alcohol (PVA), histoacryl
glue, and liquid polymer (Onyx((r))). Two cases of swelling dissection with
volume progression over time came to our observation. Both patients (45 and 70
year-old women) were studied with neck ultrasound imaging and computed tomography
(CT) and/or magnetic resonance (MR). In both cases the radiological
investigations confirmed the clinical suspicion of carotid paraganglioma. Both
patients were sent for angiography control and preoperative devascularization of
the lesion. The treatment was performed under general anesthesia using, depending
on the type of tumor vasculature, in case 1 solid particles of PVA and histoacryl
glue, and in case 2 Onyx((r)) (Covidien, Irvine). The patients successfully
underwent excision of the lesion via cervicotomy within a week from the
embolization procedure, without any complications. The histological findings
confirmed the diagnosis of chemodectoma, and macrophage infiltrates were seen in
the regions previously embolized. At one-year follow-up, there was no evidence of
recurrent disease. The preoperative embolization of vascular lesions of the neck
represents a safe technique that yields the best results when customized over the
type of vascularization of the lesion, enabling the use of the most appropriate
materials, depending on the case to be treated.
PMID- 24355188
TI - Relationship between multidetector CT imaging of the vestibular aqueduct and
inner ear pathologies.
AB - This study investigated the relationships between morphological changes in the
vestibular aqueduct (VA) in different inner ear pathologies. Eighty-eight
patients (34 males and 54 females, ranging from seven to 88 years of age; average
age 49.2 years) with cochleovestibular disorders underwent temporal bone CT (with
a 64-channel helical CT system according to temporal bone protocol parameters;
0.6 mm slice thickness, 0.6 mm collimation, bone reconstruction algorithm). All
patients with cochleovestibular disorders who underwent temporal bone CT had been
previously divided into six different suspected clinical classes: A) suspected
pathology of the third window; B) suspected retrocochlear hearing loss; C)
defined Meniere's disease; D) labyrinth lithiasis; E) recurrent vertigo. On CT
images we analyzed the length, width and morphology of the VA, contact between
the VA and the jugular bulb (JB), the thickness of the osseous capsule covering
the semicircular canals, the pneumatization rate of the temporal bone and the
diameter of the internal auditory canal. At the end of the diagnostic work-up all
patients were grouped into six pathological classes, represented as follow: 1)
benign paroxysmal positional vertigo (BPPV), 2) recurrent vertigo (RV), 3)
enlarged vestibular aqueduct syndrome (EVAS), 4) sudden or progressive unilateral
sensorineural hearing loss (SNHL), 5) superior semicircular canal dehiscence
syndrome (SSCD), 6) recurrent vestibulocochlear symptoms in Meniere's disease. We
evaluated 176 temporal bones in 88 patients. The VA was clearly visualized in
166/176 temporal bones; in ten ears the VA was not visualized. In 14 ears (11
patients, in three of whom bilaterally) we found an enlarged VA while in 31 ears
the VA was significantly narrower. In 16 ears a dehiscence of the JB with the
vestibular or cochlear aqueduct was noted. In all six patients with suspected
EVAS we found a AV wider than 1.5 mm on CT scans; moreover CT identified four
patients with large VA and ill-defined clinical symptoms. Most patients with BPPV
(11 patients, Class 1) we did not find any VA abnormalities on CT scans,
confirming the clinical diagnosis in ten patients; in the remaining patients we
found an enlarged VA, not clinically suspected. In the RV class (eight patients,
Class 2) we found three patients with negative CT scans, two patients with narrow
aqueduct and subsequently reclassified as Meniere's disease patients, and three
patients with ectasic JB dehiscence with the VA. In patients suffering from SNHL
we found no statistically significant correlation with the morphological
abnormalities. The clinical suspicion of SSCD was confirmed by CT in 11/13
patients (84.6 %); in addition another seven patients showed a thinning or
dehiscence of the superior semicircular canals as the prevailing alteration on CT
scans, and were reclassified in this group. Meniere's disease symptoms were
correlated with a VA alteration in more than half of the cases; the most striking
finding in this class was that the VA was significantly narrower (21 patients).
Our study demonstrates that alterations of the VA morphology are not only related
to EVAS but are also found in other inner ear pathologies such as Meniere's
disease. Furthermore, MDCT may confirm the presence of correlations between the
morphology of inner ear structures such as VA, semicircular canals or JB
dehiscence, and alterations of vestibulocochlear function.
PMID- 24355189
TI - Delayed post-traumatic fronto-ethmoidal sinus mucocele evaluated with short and
long TE MR spectroscopy.
AB - Mucoceles are slow-growing, benign, expansile, mucoid-filled masses developing
after obstruction of the sinus ostium. Late post-traumatic mucoceles are
relatively rare entities and the literature is limited to single case reports. We
describe an unusual case of post-traumatic fronto-ethmoidal mucocele, evaluated
with computed tomography (CT), magnetic resonance imaging (MRI) and proton MR
spectroscopy ((1)H-MRS). As a contribution to the diagnostic work-up of the
mucocele, (1)H-MRS demonstrates a dominant peak at 2.0 ppm at long echo time (TE)
and an additional component at 3.8 ppm at short TE due to mucus glycoprotein
compounds of the mucocele.
PMID- 24355190
TI - MRI of the brachial plexus: modified imaging technique leading to a better
characterization of its anatomy and pathology.
AB - Magnetic resonance imaging (MRI) is the imaging modality of choice for the
evaluation of the brachial plexus due to its superior soft tissue resolution and
multiplanar capabilities. The evaluation of the brachial plexus however
represents a diagnostic challenge for the clinician and the radiologist. The
imaging assessment of the brachial plexus, in particular, has been traditionally
challenging due to the complexity of its anatomy, its distribution in space and
due to technical factors. Herein, we describe a modified technique used in our
institution for the evaluation of the brachial plexus which led to a substantial
decrease in scanning time and to better visualization of all the segments of the
brachial plexus from the roots to the branches, in only one or two images,
facilitating therefore the understanding of the anatomy and the interpretation of
the study. To our knowledge, we are the first group to describe this technique of
imaging the brachial plexus. We illustrate the benefit of this modified technique
with an example of a patient with a lesion in the proximal branches of the left
brachial plexus that was clinically suspected but missed on conventional brachial
plexus imaging for six consecutive years. In addition, we review the common and
infrequent benign and malignant pathology that can affect the brachial plexus.
PMID- 24355193
TI - Topical 0.2% rapamycin to treat facial angiofibromas and hypomelanotic macules in
tuberous sclerosis.
PMID- 24355194
TI - Prevalence, distribution, and viral burden of all 15 high-risk human
papillomavirus types in adenosquamous carcinoma of the uterine cervix: a
multiplex real-time polymerase chain reaction-based study.
AB - Human papillomavirus (HPV) 16 and 18 are the types most commonly found in
cervical adenosquamous carcinoma. Multiple HPV types have been found in cervical
adenocarcinoma but not in the adenosquamous variant. Type-specific detection of
high-risk (HR) HPV allows the detection of co-infection by multiple HPV types and
assessment of viral load per cell. Our aim was to identify and quantify all HR
HPV types in cervical adenosquamous carcinoma and to correlate viral loads with
prognosis-related histologic features. All 15 HR HPV types were tested for by
multiplex real-time polymerase chain reaction, and standard curves were created
for each type. Viral loads were determined retrospectively. Prognosis-related
histologic features were correlated with specific HPV types and the viral loads.
A total of 80% of the tumors examined expressed HPV. Types 16/18 were detected in
86% of these cases, whereas the remaining 14% of the positive cases were infected
by other types. A single type of virus was detected in 67% of cases, 2 in 29%,
and 3 in 4%. Poor prognostic features were seen in 84.6% of the tumors infected
with HPV 16, 46% of those infected with HPV 18, and 100% of those infected with
other types. As expected, HPV 16, HPV 18, or both were the most frequent viral
types; HPV 73 was the next most frequent type. Multiple HPV types were detected
in 33% of the tumors. Non-HPV 16/18 cases had low viral loads, but all of these
had poor prognosis-related histologic features. Two of the three recurrent cases
had multiple viral types.
PMID- 24355195
TI - African Americans with oropharyngeal carcinoma have significantly poorer outcomes
despite similar rates of human papillomavirus-mediated carcinogenesis.
AB - We examined racial disparities among 102 oropharyngeal carcinoma (OPC) patients
(30 African Americans and 72 whites) comparing rates of transcriptionally active
human papillomavirus (HPV)16/18 and p16(INK4a) overexpression, with times to
disease progression and disease-specific survival (DSS). Expression of HPV16/18
transcripts was assessed by reverse transcription and polymerase chain reaction
using type-specific E6/E7 primers; p16(INK4a) was evaluated by
immunohistochemistry. African Americans were significantly more likely to present
with high T stage disease and receive nonsurgical treatment. HPV16/18 was present
in 63% of patients; no racial differences were observed. Silenced p16(INK4a) in
OPC was significantly more common in African Americans (15/24) than in whites
(20/69) (P = .004) and in HPV16+ African Americans (6/24) than in HPV+ whites
(2/42) (P = .023). Kaplan-Meier analysis for DSS revealed a protective effect for
p16(INK4a) overexpression (P = .0028; hazard ratio [HR], 0.23), HPV16+ (P = .036;
HR, 0.38), and whites (P = .0039; HR, 0.27). Shorter DSS was associated with
primary definitive chemoradiation (P = .019; HR, 3.49) and T3/T4 disease (P =
.0001; HR, 7.75). A protective effect with respect to disease progression was
observed for HPV16+ (P = .007; HR, 0.27), whites (P = .0006; HR, 0.197), and
p16(INK4a) overexpression (P = .0001; HR, 0.116). African Americans with OPC
experience poorer outcomes likely due to p16(INK4a) silencing, higher T stage,
and nonsurgical treatment but not lower rates of transcriptionally active
HPV16/18.
PMID- 24355196
TI - High-stage urachal adenocarcinoma can be associated with microsatellite
instability and KRAS mutations.
AB - Urachal adenocarcinoma (UAC) is a rare tumor of the urinary bladder, which can
show intestinal, mucinous, and signet ring cell histology. The morphology is
similar to that of colorectal adenocarcinoma (CAC). Microsatellite instability
(MSI), KRAS, and BRAF have been more extensively studied in CAC. What is not
known is whether UAC in its morphologic similarity to CAC could show
immunohistochemical features of MSI along with KRAS- and BRAF-activating
mutations. A retrospective review of institutional archives for UAC cases found 7
cases, all of which were high stage. Most (6/7) of our UAC cases showed evidence
of MSI or mutations of KRAS. No cases showed a BRAF mutation at codon 600. Of the
cases that demonstrated MSI, 1 showed mutS homolog 2 and mutS homolog 6 loss, and
2 showed PMS2 (postmeiotic segregation increased 2) loss. Of the remaining 4
cases, 3 showed KRAS mutations at codon 12. Our UAC series showed mutual
exclusivity of MSI and KRAS mutations. Furthermore, our UAC cases with KRAS
mutations showed markedly better overall survival (mean, 101.7 versus 6.5 months;
P = .035). Thus, our study justifies ancillary testing for MSI and KRAS in UAC,
particularly when there is high-stage and mucinous histology, but a larger multi
institutional accruement of UAC cases is necessary to further validate our novel
findings.
PMID- 24355198
TI - Fracture near press-on interlocking enhances callus mineralisation in a sheep
midshaft tibia osteotomy model.
AB - INTRODUCTION: Factors which impair fracture healing after intramedullary (IM)
nailing of long bone fractures range from surgical and biological factors to
mechanical parameters. Mechanical parameters known to prolong bony consolidation
are share forces at the site of the fracture. Fracture near press-on interlocking
reduces share forces directly at the fracture site and is hypothesised to enhance
callus mineralisation. A sheep model of midshaft tibia osteotomies evaluates the
technique. MATERIALS AND METHODS: Fracture near interlocking was achieved by
surfacing a custom made nail with special hutches that enable firm screw seating
on top of the nail ("golf ball" structure). Virtual (fine element analysis (FEA))
and biomechanical pilot tests were completed before in vivo application in 12
adult female German black sheep. Midshaft tibia osteotomy was performed creating
a subcritical 7 mm gap for delay in union. One group (n=6) was treated with
reamed IM nailing employing the custom made nail and in addition to proximal and
distal standard interlocking a fracture near press on interlocking was employed.
A second group of six sheep without additional press on interlocking served as
control. 10 weeks after operation the quality of fracture healing was determined
by micro-CT. RESULTS: The FEA showed that axial loading up to 4000N did not lead
to implant fatigue. Fracture near press on interlocking led to significantly more
callus mineralisation compared to the conventional interlocking procedure (0.567
g/cm(3) +/- 0.106 g/cm(3) versus 0.434 g/cm(3) +/- 0.0836 g/cm(3), p=0.043).
CONCLUSIONS: Fracture near press on interlocking increases callus mineralisation
in a subcritical osteotomy model in sheep. The results indicate that the
reduction of share forces at the fracture site after nailing procedures may be
effective in reducing the time until bony consolidation.
PMID- 24355197
TI - Characteristics associated with informed consent for genetic studies in the
ACCORD trial.
AB - BACKGROUND: Prior studies found that some groups have lower genetic consent rates
than others. Participant consent for genetic studies enables randomized trials to
examine effects of interventions compared to control in participants with
different genotypes. METHODS: Unadjusted and multivariate associations between
genetic consent rates and participant, study, and consent characteristics in 9573
participants approached for genetics consent in the multicenter Action to Control
Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics
consent. RESULTS: Eighty-nine percent of eligible participants consented to
genetic studies ("Any Consent") and 64.7% consented to studies of any genes by
any investigator ("Full Consent"), with similar rates in randomized groups.
Controlling for multiple characteristics, African-Americans had lower consent
rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR
= 0.67, p < 0.0001). Those with high school or higher education level had higher
rates than less than high school graduates (Full Consent ORs 1.41-1.69, p-values
< 0.0001). Consent rates were lower when genetics consent was separate from the
main trial consent on the same day (Any Consent OR 0.30; Full Consent OR 0.52, p
values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full
Consent OR 0.76, p = 0.0002). CONCLUSION: High rates of consent for genetic
studies can be obtained in complex randomized trials, with lower consent rates in
African-Americans, in participants with less than high-school education, and for
sharing samples with other investigators. A genetics consent separated from the
main trial consent was associated with lower consent rates.
PMID- 24355199
TI - Evaluation of membrane bioreactor for advanced treatment of industrial wastewater
and reverse osmosis pretreatment.
AB - The evaluation of a membrane bioreactor (MBR) for pretreatment of reverse osmosis
(RO) in order to reuse and reclamation of industrial town wastewater treatment
plant was investigated in this study. Performance of MBR effluent through water
quality in term of parameters such as chemical oxygen demand (COD), total
suspended solids (TSS), total nitrogen (TN) and total coliform (TC) were
measured. Also Silt density index (SDI) was used as indicator for RO feed water.
The results of this study demonstrated that MBR produce a high quality permeate
water. Approximately 75%, 98%, 74% and 99.9% removal of COD, TSS, TN and TC were
recorded, respectively. Also SDI of the permeate effluent from membrane was below
3 for most of the times. It means that pilot yield a high quality treated
effluent from the membrane module which can be used as RO feed water.
PMID- 24355200
TI - Ethnic disparities in the association of impaired fasting glucose with the 10
year cumulative incidence of type 2 diabetes.
AB - AIMS: Evidence of ethnic disparities in the conversion of prediabetes to type 2
diabetes is scarce. We studied the association of impaired fasting glucose (IFG)
and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2
diabetes in three ethnic groups. METHODS: We analyzed data for 90 South-Asian
Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in
the periods 2001-2003 and 2011-2012. We excluded those with type 2 diabetes or
missing FPG data. We defined baseline IFG as FPG of 5.7-6.9 mmol/L. We defined
type 2 diabetes at follow-up as FPG >= 7.0 mmol/L, HbA1c >= 48 mmol/mol (6.5%),
or self-reported type 2 diabetes. RESULTS: 10-Year cumulative incidences of type
2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic
Dutch, 4.5% (p<0.05). The adjusted association of baseline IFG and FPG with the
10-year cumulative incidence of type 2 diabetes was stronger for South-Asian
Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to
normoglycaemia) ORs were 11.1 [3.0-40.8] for South-Asian Surinamese, 5.1 [2.0
13.3] for African-Surinamese, and 2.2 [0.5-10.1] for ethnic Dutch. CONCLUSIONS:
The 10-year cumulative incidence of type 2 diabetes was higher and associations
with baseline IFG and FPG were stronger among South-Asian Surinamese and African
Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2
diabetes in South-Asians and suggest more rapid conversion in populations of
South-Asian origin and (to a lesser extent) African origin than European origin.
PMID- 24355201
TI - Effect of Lon protease knockdown on mitochondrial function in HeLa cells.
AB - ATP-dependent proteases are currently emerging as key regulators of mitochondrial
functions. Among these proteolytic systems, Lon protease is involved in the
control of selective protein turnover in the mitochondrial matrix. In the absence
of Lon, yeast cells have been shown to accumulate electron-dense inclusion bodies
in the matrix space, to loose integrity of mitochondrial genome and to be
respiratory deficient. In order to address the role of Lon in mitochondrial
functionality in human cells, we have set up a HeLa cell line stably transfected
with a vector expressing a shRNA under the control of a promoter which is
inducible with doxycycline. We have demonstrated that reduction of Lon protease
results in a mild phenotype in this cell line in contrast with what have been
observed in other cell types such as WI-38 fibroblasts. Nevertheless, deficiency
in Lon protease led to an increase in ROS production and to an accumulation of
carbonylated protein in the mitochondria. Our study suggests that Lon protease
has a wide variety of targets and is likely to play different roles depending of
the cell type.
PMID- 24355202
TI - Effect of environmental conditions on various enzyme activities and
triacylglycerol contents in cultures of the freshwater diatom, Asterionella
formosa (Bacillariophyceae).
AB - A detailed analysis of triacylglycerols (TAGs) contents, fatty acid patterns and
key enzyme activities in the freshwater diatom Asterionella formosa was performed
under various conditions, including nitrate, iron and silicon limitation (stress
conditions), or bicarbonate and phytohormones supplementation (stimulation
conditions). Of all the conditions tested, the addition of bicarbonate produced
the greatest increase (5-fold) in TAGs contents compared to the control while the
biomass increased. The addition of phytohormones also allowed a significant
increase in TAGs of about 3-fold while the biomass increased. Silicon, unlike
iron and nitrate limitation, also triggered a significant increase in TAGs
contents of 3.5-fold but negatively affected the biomass. Analysis of fatty acid
profiles showed that the mono-unsaturated C16:1 fatty acid was the most abundant
in A. formosa, followed by C16:0, C14:0 and eicosapentaenoic acid (EPA; C20:5 n
3). EPA levels were found to increase under nitrate and iron limitation.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoribulokinase (PRK),
phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH) and malate
dehydrogenase (MDH) activities differed with growth conditions. Most enzymes were
up-regulated in stimulated cells while in the case of stressed cells, the pattern
of activities was more variable. Detailed analysis of all enzyme activities
showed that the most important enzyme among those tested was GAPDH which could be
a good candidate for genetic engineering of high lipid-producing algae. This
study provides a better understanding of key enzymes and biochemical pathways
involved in lipid accumulation processes in diatoms.
PMID- 24355203
TI - Cytotoxic effects of dillapiole on MDA-MB-231 cells involve the induction of
apoptosis through the mitochondrial pathway by inducing an oxidative stress while
altering the cytoskeleton network.
AB - Breast cancer is the world's leading cause of death among women. This situation
imposes an urgent development of more selective and less toxic agents. The use of
natural molecular fingerprints as sources for new bioactive chemical entities has
proven to be a quite promising and efficient method. Here, we have demonstrated
for the first time that dillapiole has broad cytotoxic effects against a variety
tumor cells. For instance, we found that it can act as a pro-oxidant compound
through the induction of reactive oxygen species (ROS) release in MDA-MB-231
cells. We also demonstrated that dillapiole exhibits anti-proliferative
properties, arresting cells at the G0/G1 phase and its antimigration effects can
be associated with the disruption of actin filaments, which in turn can prevent
tumor cell proliferation. Molecular modeling studies corroborated the biological
findings and suggested that dillapiole may present a good pharmacokinetic
profile, mainly because its hydrophobic character, which can facilitate its
diffusion through tumor cell membranes. All these findings support the fact that
dillapiole is a promising anticancer agent.
PMID- 24355205
TI - Fungal inhibitors of proteolytic enzymes: classification, properties, possible
biological roles, and perspectives for practical use.
AB - Peptidase inhibitors are ubiquitous regulatory proteins controlling catalytic
activity of proteolytic enzymes. Interest in these proteins increased
substantially after it became clear that they can be used for therapy of various
important diseases including cancer, malaria, and autoimmune and
neurodegenerative diseases. In this review we summarize available data on
peptidase inhibitors from fungi, emphasizing their properties, biological role,
and possible practical applications of these proteins in the future. A number of
fungal peptidase inhibitors with unique structure and specificity of action have
no sequence homology with other classes of peptidase inhibitors, thus
representing new and specific candidates for therapeutic use. The main
classifications of inhibitors in current use are considered. Available data on
structure, mechanisms and conditions of action, and diversity of functions of
peptidase inhibitors of fungi are analyzed. It is mentioned that on one side the
unique properties of some inhibitors can be used for selective inhibition of
peptidases responsible for initiation and development of pathogenic processes. On
the other side, general inhibitory activity of other inhibitors towards
peptidases of various catalytic classes might be able to provide efficient
defense of transgenic plants against insect pests by overcoming compensatory
synthesis of new peptidases by these pests in response to introduction of a
fungal inhibitor. Together, the data analyzed in this review reveal that fungal
inhibitors extend the spectrum of known peptidase inhibitors potentially suitable
for use in medicine and agriculture.
PMID- 24355204
TI - The molecular genetics of coenzyme Q biosynthesis in health and disease.
AB - Coenzyme Q, or ubiquinone, is an endogenously synthesized lipid-soluble
antioxidant that plays a major role in the mitochondrial respiratory chain.
Although extensively studied for decades, recent data on coenzyme Q have painted
an exciting albeit incomplete picture of the multiple facets of this molecule's
function. In humans, mutations in the genes involved in the biosynthesis of
coenzyme Q lead to a heterogeneous group of rare disorders, with most often
severe and debilitating symptoms. In this review, we describe the current
understanding of coenzyme Q biosynthesis, provide a detailed overview of human
coenzyme Q deficiencies and discuss the existing mouse models for coenzyme Q
deficiency. Furthermore, we briefly examine the current state of affairs in non
mitochondrial coenzyme Q functions and the latter's link to statin.
PMID- 24355206
TI - Primary leptomeningeal melanocytosis presenting as chronic meningitis.
AB - We report a patient with primary leptomeningeal melanocytosis presenting as
chronic meningitis. A previously healthy 27-year-old man presented with 2 months
of severe headaches and photophobia. A lumbar puncture was notable for a highly
elevated cerebrospinal fluid (CSF) protein level without pleocytosis. Imaging at
the time of admission suggested only meningitis without the presence of
parenchymal lesions. On the basis of the CSF findings, early meningeal biopsy was
performed, leading to the diagnosis of a meningeal melanocytic neoplasm. Early
meningeal biopsy should be considered in patients with meningitis when the CSF
profile suggests the possibility of a central nervous system neoplasm.
PMID- 24355207
TI - Effectiveness of radiotherapy for elderly patients with anaplastic gliomas.
AB - Postoperative radiotherapy (RT) is utilized routinely in the management of
anaplastic World Health Organization Grade III gliomas (AG), including anaplastic
astrocytoma (AA) and anaplastic oligodendroglioma (AO). However, the optimal role
of RT in elderly AG patients remains controversial. We evaluated the
effectiveness of RT in elderly AG patients using a national cancer registry. The
USA Surveillance, Epidemiology, and End Results database (1990-2008) was used to
query patients over 70 years of age with AA or AO. Independent predictors of
overall survival were determined using a multivariate Cox proportional hazards
model. Among 390 elderly patients with AG, 333 (85%) had AA and 57 (15%) had AO.
Approximately two-thirds of AA patients (64%) and AO patients (65%) received RT.
Most AO patients (58%) and many AA patients (41%) underwent surgical resection;
the remainder had biopsy. The median overall survival for all patients who
underwent RT was 6 months (95% confidence interval [CI], 5-7 months) versus 2
months (95% CI 1-6) in patients who did not have RT. Patients who had gross total
resection (GTR) plus RT had a median overall survival of 11 months (95% CI 7-14).
Multivariate analysis for all patients showed that undergoing RT was
significantly associated with improved survival (hazard ratio [HR] 0.52,
p<.0001). AA tumor type (HR 1.37, p=.03) was associated with worse survival than
AO tumor type; female sex (HR 0.59, p<.0001) and being married (HR 0.66, p=.002)
significantly improved survival. Patients that underwent GTR had a significant
reduction in the hazards of mortality compared to biopsy (HR 0.72, p=.04).
Elderly AG patients undergoing RT had better overall survival compared to
patients who did not receive RT. Treatment strategies involving maximal safe
resection plus RT should be considered in the optimal management of AG in elderly
patients.
PMID- 24355208
TI - Effects of CO2 on the tolerance of photosynthesis to heat stress can be affected
by photosynthetic pathway and nitrogen.
AB - PREMISE OF THE STUDY: Determining effects of elevated CO2 and N on photosynthetic
thermotolerance is critical for predicting plant responses to global warming.
METHODS: We grew Hordeum vulgare (barley, C3) and Zea mays (corn, C4) at current
or elevated CO2 (370, 700 ppm) and limiting or optimal soil N (0.5, 7.5 mmol/L).
We assessed thermotolerance of net photosynthesis (Pn), photosystem II efficiency
in the light (Fv'/Fm'), photochemical quenching (qp), carboxylation efficiency
(CE), and content of rubisco activase and major heat-shock proteins (HSPs). KEY
RESULTS: For barley, elevated CO2 had no effect on Pn, qp, and CE at both high
and low N and only a positive effect on Fv'/Fm' at high N. However, for corn, Pn,
Fv'/Fm', qp, and CE were decreased substantially by elevated CO2 under high and
low N, with greater decreases at high N for all but qp. The negative effects of
high CO2 during heat stress on photosynthesis were correlated with rubisco
activase and HSPs content, which decreased with heat stress, especially for low-N
corn. CONCLUSION: These results indicate that stimulatory effects of elevated CO2
at normal temperatures on photosynthesis and growth (only found for high-N
barley) may be partly offset by neutral or negative effects during heat stress,
especially for C4 species. Thus, CO2 and N effects on photosynthetic
thermotolerance may contribute to changes in plant productivity, distribution,
and diversity in future.
PMID- 24355209
TI - Synthesis and molecular modeling of six novel monastrol analogues: evaluation of
cytotoxicity and kinesin inhibitory activity against HeLa cell line.
AB - BACKGROUND AND THE PURPOSE OF THE STUDY: A common approach in cancer chemotherapy
is development of drugs that interrupt the mitosis phase of cell division.
Dimethylenastron is a known kinesin inhibitor. In this study, six novel
dimethylenastron analogues (4a-f), in which 3-hydroxyphenyl substituent has been
replaced with substituted benzylimidazolyl, were synthesized through Biginelli
reaction. METHODS: Six novel Biginelli compounds (4a-f) were synthesized through
one step Biginelli reaction of imidazole aldehydes (3a-c), dimedone and urea or
thioura. In vitro cytotoxicities of prepared compounds were investigated using
MTT assay. Furthermore the ELIPA kit was implemented to study inhibitory effects
of synthesized compounds on ATPase activity of kinesin by measuring of organic
phosphate. RESULTS: Our results indicated that analogue 4c is the most toxic and
analogues 4f, 4b and dimethylenasteron were less cytotoxic in compare with other
analogues. On the other hand, analogue 4a, 4b, 4c and 4e showed stronger Kinesin
inhibition as compared with analogue 4f and dimethylenasteron. None of
synthesized compounds were as potent kinesin inhibitor as Taxol. Docking analysis
revealed that hydrogen bond formation and hydrophobic interactions were the key
factors affecting inhibitory effects of these compounds. CONCLUSION: Newly
synthesized compounds were found to have moderate to good cytotoxicity against
HeLa cancer cell. Our results may be helpful in further design of
dihydropyrimidine as potential anticancer agents.
PMID- 24355210
TI - Correlation of lactate dehydrogenase isoenzyme profile with outcome in patients
with advanced colorectal cancer treated with chemotherapy and bevacizumab or
cediranib: Retrospective analysis of the HORIZON I study.
AB - INTRODUCTION: Bevacizumab improves outcome for patients with advanced colorectal
cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar
outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor
of vascular endothelial growth factor (VEGF) receptor, as treatment of advanced
CRC. The spectrum of lactate dehydrogenase (LDH) isoenzyme expression was
examined in serum samples of HORIZON I participants to identify biomarkers
predictive of efficacy of VEGF pathway inhibitors. MATERIALS AND METHODS: Total
LDH levels, as well as LDH isoenzyme levels in frozen baseline serum samples,
were retrospectively evaluated. Total LDH serum levels measured during the study,
progression-free survival (PFS), and overall survival (OS) were available from
the HORIZON I study data. RESULTS: Total LDH levels measured in the frozen serum
samples correlated with those measured in fresh samples. The expected reciprocal
correlation was found between hypoxic and oxic LDH isoenzymes. High total LDH
correlated with shorter PFS, and high hypoxia-related LDH isoenzymes correlated
with shorter PFS and OS. The difference in outcome of the cediranib-treated
patients vs. those treated with bevacizumab was not substantially different in
the various LDH isoform expression subgroups. In patients with a hypoxic LDH
pattern of expression, there was a nonsignificant trend of better outcome in
cediranib-treated patients. CONCLUSION: Evaluation of total LDH and its isoforms
in frozen serum samples is feasible. High total LDH and high hypoxic LDH
isoenzymes were associated with poor prognosis. Further studies are needed to
evaluate the predictive value of LDH isoenzyme expression pattern for VEGF
pathway inhibition efficacy.
PMID- 24355212
TI - Signaling steps in the induction of genomic damage by insulin in colon and kidney
cells.
AB - Diabetes mellitus (DM), a disease with almost 350 million people affected
worldwide, will be the seventh leading cause of death by 2030. Diabetic patients
develop various types of complications, among them an increased rate of
malignancies. Studies reported the strong correlation between DM and several
cancer types, of which colon and kidney cancers are the most common.
Hyperinsulinemia, the high insulin blood level characteristic of early diabetes
type 2, was identified as a risk factor for cancer development. In previous
studies, we showed that an elevated insulin level can induce oxidative stress,
resulting in DNA damage in colon cells in vitro and in kidney cells in vitro and
in vivo. In the present study, we elucidate the signaling pathway of insulin
mediated genotoxicity, which is effective through oxidative stress induction in
colon and kidney. The signaling mechanism is starting by phosphorylation of the
insulin and insulin-like growth factor-1 receptors, followed by activation of
phosphatidylinositide 3-kinase (PI3K), which in turn activates AKT. Subsequently,
mitochondria and nicotinamide adenine dinucleotide phosphate oxidase (NADPH)
isoforms (Nox1 and Nox4 in colon and kidney, respectively) are activated for
reactive oxygen species (ROS) production, and the resulting excess ROS can attack
the DNA, causing DNA oxidation. We conclude that hyperinsulinemia represents an
important risk factor for cancer initiation or progression as well as a target
for cancer prevention in diabetic patients.
PMID- 24355213
TI - Simultaneous determination of SYL-1119 and SYL-1119-P in rat plasma using HPLC
coupled with tandem mass spectrometry.
AB - SYL-1119 is a sphingosine-1-phosphate receptor 1 modulator for the treatment of
autoimmune disease with better selectivity, while SYL-1119-P is its active
phosphate. A sensitive and specific liquid chromatography-tandem mass
spectrometry method was developed and validated for the simultaneous
determination of SYL-1119 and SYL-1119-P in rat plasma. SYL-1110, an analogue of
SYL-1119, was used as the internal standard. Plasma samples were prepared by
protein precipitation using acetonitrile. The analytes and internal standard were
separated on a Zorbax SB-C18 column (3.5MUm, 100mm*2.1mm) with a gradient mobile
phase consisting of methanol and water containing 0.1% formic acid at a flow rate
of 0.2ml/min with an operating temperature of 20 degrees C. The detection was
performed on a triple quadrupole tandem mass spectrometer with positive
electrospray ionization in multiple reaction monitoring mode of the transitions
at m/z 364->259 for SYL-1119, m/z 444->259 for SYL-1119-P, and m/z 378->273 for
the IS. Calibration curves were linear in the range of 0.2-50ng/ml for SYL-1119
and 10-1000ng/ml for SYL-1119-P. The lower limit of quantification (LLOQ) was
0.2ng/ml for SYL-1119 and 10ng/ml for SYL-1119-P. The intra- and inter-day
precisions were 5.4-12.8% for two analytes with accuracies within +/-10%. The
recoveries for two compounds were 91.3-104.5%. The analytes were proved to be
stable during all sample storage, preparation, and analytic procedures. The
method was successfully applied to the pharmacokinetic study of SYL-1119 and SYL
1119-P in rats after oral administration of SYL-1119.
PMID- 24355211
TI - Antisense oligonucleotide against GSK-3beta in brain of SAMP8 mice improves
learning and memory and decreases oxidative stress: Involvement of transcription
factor Nrf2 and implications for Alzheimer disease.
AB - Glycogen synthase kinase (GSK)-3beta is a multifunctional protein that has been
implicated in the pathological characteristics of Alzheimer's disease (AD),
including the heightened levels of neurofibrillary tangles, amyloid-beta (Abeta),
and neurodegeneration. In this study we used 12-month-old SAMP8 mice, an AD
model, to examine the effects GSK-3beta may cause regarding the cognitive
impairment and oxidative stress associated with AD. To suppress the level of GSK
3beta, SAMP8 mice were treated with an antisense oligonucleotide (GAO) directed
at this kinase. We measured a decreased level of GSK-3beta in the cortex of the
mice, indicating the success of the antisense treatment. Learning and memory
assessments of the SAMP8 mice were tested post-antisense treatment using an
aversive T-maze and object recognition test, both of which observably improved.
In cortex samples of the SAMP8 mice, decreased levels of protein carbonyl and
protein-bound HNE were measured, indicating decreased oxidative stress. Nuclear
factor erythroid-2-related factor 2 (Nrf2) is a transcription factor known to
increase the level of many antioxidants, including glutathione-S transferase
(GST), and is negatively regulated by the activity of GSK-3beta. Our results
indicated the increased nuclear localization of Nrf2 and level of GST, suggesting
the increased activity of the transcription factor as a result of GSK-3beta
suppression, consistent with the decreased oxidative stress observed. Consistent
with the improved learning and memory, and consistent with GSK-3b being a tau
kinase, we observed decreased tau phosphorylation in brain of GAO-treated SAMP8
mice compared to that of RAO-treated SAMP8 mice. Lastly, we examined the ability
of GAO to cross the blood-brain barrier and determined it to be possible. The
results presented in this study demonstrate that reducing GSK-3 with a
phosphorothionated antisense against GSK-3 improves learning and memory, reduces
oxidative stress, possibly coincident with increased levels of the antioxidant
transcriptional activity of Nrf2, and decreases tau phosphorylation. Our study
supports the notion of GAO as a possible treatment for AD.
PMID- 24355214
TI - Separation of steroids using vegetable oils in microemulsion electrokinetic
capillary chromatography.
AB - The steroids, hydrocortisone, androstenedione, 17-alpha-hydroxyprogesterone,
testosterone, 17-alpha-methyltestosterone, and progesterone were separated with
microemulsion electrokinetic chromatography (MEEKC) and detected with UV
absorption. The microemulsion phases were prepared from both artificial and
vegetable oils, from them the first was made of alkane and alcohol and the latter
from colza, olive, linseed, and walnut oils. The electrolyte solutions were made
to emulsions using sodium dodecyl sulfate and alkaline tetraborate. The solution
mixtures made from ethyl acetate, sodium dodecyl sulfate, 1-butanol,
acetonitrile, and sodium tetraborate were used as the reference solutions to
evaluate the performance of the vegetable oil emulsions. Our study showed that
the lipophilic organic phase in the microemulsion did provide resolution
improvements but not selectivity changes. The results also correlate with real
interactions of the steroids with the lipophilic organic microemulsion phase. The
quality of the oils between the manufacturers did not have importance, which was
noticed from the equal behavior of the steroids in the vegetable oil emulsions.
Detection limits of the steroids in vegetable oil emulsions were at the level of
0.20-0.43MUg/L. Thus, they were 2-10 times higher than the concentrations in the
partial filling micellar electrokinetic chromatography (PF-MEKC), which we have
obtained earlier. The repeatability (RSD%) of the electrophoretic mobilities of
the steroids was between 0.50 and 3.70. The RSD% values between the inter-day
separations were below 1%, but when walnut and olive oils were used the values
exceeded even 10%.
PMID- 24355216
TI - Modeling the morphodynamic galectin patterning network of the developing avian
limb skeleton.
AB - We present a mathematical model for the morphogenesis and patterning of the
mesenchymal condensations that serve as primordia of the avian limb skeleton. The
model is based on the experimentally established dynamics of a multiscale
regulatory network consisting of two glycan-binding proteins expressed early in
limb development: CG (chicken galectin)-1A, CG-8 and their counterreceptors that
determine the formation, size, number and spacing of the "protocondensations"
that give rise to the condensations and subsequently the cartilaginous elements
that serve as the templates of the bones. The model, a system of partial
differential and integro-differential equations containing a flux term to
represent local adhesion gradients, is simulated in a "full" and a "reduced" form
to confirm that the system has pattern-forming capabilities and to explore the
nature of the patterning instability. The full model recapitulates qualitatively
and quantitatively the experimental results of network perturbation and leads to
new predictions, which are verified by further experimentation. The reduced model
is used to demonstrate that the patterning process is inherently morphodynamic,
with cell motility being intrinsic to it. Furthermore, subtle relationships
between cell movement and the positive and negative interactions between the
morphogens produce regular patterns without the requirement for activators and
inhibitors with widely separated diffusion coefficients. The described mechanism
thus represents an extension of the category of activator-inhibitor processes
capable of generating biological patterns with repetitive elements beyond the
morphostatic mechanisms of the Turing/Gierer-Meinhardt type.
PMID- 24355217
TI - A relaxed modification of the Rappaport model for cytokinesis.
PMID- 24355215
TI - Rapid and simultaneous quantitation of prostanoids by UPLC-MS/MS in rat brain.
AB - The metabolites of arachidonic acid (AA) produced from the cyclooxygenase (COX)
pathway, collectively termed as prostanoids, and from the CYP 450 pathway,
eicosanoids, have been implicated in various neuro-degenerative and
neuroinflammatory diseases. This study developed a quantitative UPLC-MS/MS method
to simultaneously measure 11 prostanoids including prostaglandins and
cyclopentenone metabolites in the rat brain cortical tissue. Linear calibration
curves ranging from 0.104 to 33.3ng/ml were validated. The inter-day and intra
day variance for all metabolites was less than 15%. The extraction recovery
efficiency and matrix (deionized water) effects measured at 12.5ng/ml (750pg on
column) ranged from 88 to 100% and 3 to 14%, respectively, with CV% values below
20%. Additionally, applying the processing and extraction conditions of this
method to our previous CYP450 eicosanoids method resulted in overall improvement
in extraction recovery and reduction in matrix effects at low (0.417ng/ml) and
high (8.33ng/ml) concentrations. In rat brain cortical tissue samples,
concentrations of prostanoids ranged from 10.2 to 937pmol/g wet tissue and
concentration of eicosanoids ranged from 2.23 to 793pmol/g wet tissue. These data
demonstrate that the successive measurement of prostanoids and eicosanoids from a
single extracted sample of rat brain tissue can be achieved with a UPLC-MS/MS
system and that this method is necessary for evaluation of these metabolites to
delineate their role in various neuroinflammatory and cerebrovascular disorders.
PMID- 24355218
TI - Second European multi-disciplinary conference of national strategies for
Chlamydia trach. and human papillomavirus NSCP conf. in Berlin, 2013 enhanced
detection, management and surveillance of sexually transmitted infections in
Europe are essential!
AB - There is a need for updated guidance on detection, management and surveillance of
sexually transmitted infections (STIs). Chlamydia, gonorrhoea and
syphilisreporting needs to be mandatory in more European countries to aid
collection of data. More widespread Chlamydia screening is needed in many
countries as this is the only way to reduce complications. The role of Human
Papillomavirus (HPV) screening in a situation where the prevalence of HPV
infection has dropped significantly was also discussed in the context of the high
cost of screening, the need for a relatively complex infrastructure, particularly
in developing countries, and falling vaccination costs. An integrated HPV
vaccination and screening policy could be the most appropriate with vaccination
at 9-13 years as recommended by WHO and a single HPV screen at 35-39 years,
possibly repeated thereafter every 10 years. Female and male HPV vaccination
programmes could lead to near elimination of genital warts in both females and
males. Surveillance of STIsshould be intensified where needed; additional or
better quality data should be collected including reasons for testing,
denominator data to estimate positivity rates, diagnostic methods, concurrent
STIs, sexual orientation and country of acquisition; more analytical rather than
descriptive epidemiology is needed.
PMID- 24355219
TI - Anti-hemorrhagic agents in oral and dental practice: an update.
AB - Many oral surgeons in their daily practice have the problem of controlling
postoperative bleeding. In surgical, oral and maxillofacial practice, standard
anti-hemorrhagic protocols, especially in high risk patients, are obviously
required and need to be continuously updated. The purpose of this review is to
give a rational insight into the management of bleeding in oral and dental
practice through modern drugs and medical devices such as lysine analogues and
serine protease inhibitors, desmopressin, fibrin sealants, cyanoacrylates,
gelatins, collagen and foams, protein concentrates, recombinant factors,
complementary and alternative medicine and other compounds.
PMID- 24355220
TI - Impact of mast cells on the skin.
AB - When through the skin a foreign antigen enters it provokes an immune response and
inflammatory reaction. Mast cells are located around small vessels that are
involved in vasaldilation. They mature under the influence of local tissue to
various cytokines. Human skin mast cells play an essential role in diverse
physiological and pathological processes and mediate immediate hypersensitive
reaction and allergic diseases. Injection of anti-IgE in the skin or other agents
that directly activate mast cells may cause the decrease in vascular tone,
leakage of plasma and may lead to a fall in blood pressure with fatal
anaphylactic shock. Skin mast cells are also implicated as effector cells in
response to multiple parasites such as Leishmania which is primarily
characterized by its tissue cutaneous tropism. Activated macrophages by IFNgamma,
cytotoxic T cells, activated mast cells and several cytokines are involved in the
elimination of the parasites and immunoprotection. IL-33 is one of the latest
cytokines involved in IgE-induced anaphylaxis and in the pathogenesis of allergic
skin disorders. IL-33 has been shown in epidermis of patients with psoriasis and
its skin expression causes atopic dermatitis and it is crucial for the
development of this disease. Here we review the impact of mast cells on the skin.
PMID- 24355221
TI - Establishment of a low dose canine endotoxemia model to test anti-inflammatory
drugs: effects of prednisolone.
AB - Infusion of low doses of lipopolysaccharide (LPS) in human volunteers provides a
standardised model to study novel anti-inflammatory drugs. However, low dose
endotoxemia is not well characterised in animals larger than rodents and trials
with immunomodulating substances are scarce. We conducted a dose-finding study to
establish a canine endotoxemia model combining optimal cytokine response with
minimal burden for the animals. We thereafter evaluated the pharmacodynamics and
pharmacokinetics (PK) of prednisolone. For dose-finding, dogs randomly received a
single bolus of 0.03, 0.1 or 1.0 microg/kg BW LPS i.v. The second part was a
randomised, placebo controlled trial with 4 parallel groups. Either 0.25, 0.5 or
5mg/kgBW prednisolone or placebo were given for 3 days. On day 3, all animals
received 0.1microg/kg BW LPS i.v. Blood was sampled to measure interleukin 6 (IL
6) and tumor necrosis factor-alpha, C-reactive protein, prednisolone and cortisol
concentrations. In accordance with human endotoxemia, LPS substantially and dose
dependently increased IL-6 and TNF-alpha several 1000-fold. Prednisolone
significantly attenuated the LPS-induced IL-6 and TNF-alpha responses by a
maximum of 96 percent (p less than 0.03 for all treatment groups) and
significantly reduced peak cortisol concentrations in a dose-dependent way (p
less than 0.004 for all treatment groups). PK showed a non-linear kinetic. In
conclusion, this dog model could provide a reliable setting to test experimental
drugs for canine or human use.
PMID- 24355222
TI - Protective effect of alpha-lipoic acid on cypermethrin-induced oxidative stress
in Wistar rats.
AB - Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control
insects in the household and in agriculture. Despite beneficial roles, its
uncontrolled and repetitive application leads to unintended effects in non-target
organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid
(ALA), in the work described herein we tested the effect of a commercially
available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar
rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg
of CY for 60 days. The treatment with CY did not induce changes in either
locomotor activities or in body weight. Differences were observed on superoxide
dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established
by ALA treatment at similar levels of the placebo group. Furthermore, ALA
formulation increased glutathione (GSH) level and glutathione peroxidase (GPx)
activity. Because of the widespread use of CY, higher amounts of pesticide
residues are present in food, and a diet supplementation with ALA could be an
active free radical scavenger protecting against diseases associated with
oxidative stress.
PMID- 24355223
TI - Ambroxol inhibits neutrophil respiratory burst activated by alpha chain integrin
adhesion.
AB - The purpose of the present study was to investigate the possible anti-oxidant
effect(s) of Ambroxol on neutrophils activated by ligand-binding of the drug with
membrane-associated adhesion integrin CD11a and to estimate dose-response changes
in oxygen free radical production. The amount of free radical production by anti
CD11a- and anti-CD4-coated neutrophils stimulated with N-formyl-methionyl-leucyl
phenylalanine (FMLP) and challenged with increasing concentration of Ambroxol,
was evaluated within a time frame of 90 minutes. A significant dose-dependent
effect response of Ambroxol on O2‾ production by cells coated with anti
CD11a antibody was observed. This preliminary study opens a new perspective on
the therapeutic role of Ambroxol as an antioxidant drug and for its potential use
in controlling oxidative stress, particularly in leukocyte-dependent
inflammation.
PMID- 24355224
TI - Differential expression of immune-modulatory molecule HLA-E in non-neoplastic and
neoplastic lesions of the thyroid.
AB - Human leukocyte antigen (HLA)?E is a non-classical molecule of the
histocompatibility complex that functions as one of the main ligands of the
Natural Killer (NK) cell inhibitory receptor CD94/NKG2A and inhibits its potent
cytotoxic activity. Due to the important role of NK cells in combating neoplasm,
we hypothesized that the differential expression of HLA-E could favor the
progression of heterogeneous thyroid tumors.Using an immunohistochemistry
technique in 143 biopsies of thyroid tumors, including benign and malignant
neoplasms and goiters, we evaluated the expression of HLA-E among various tumor
types and its association with the clinicopathological factors of diseases. We
verified high HLA-E expression in all types of neoplastic tumors, although no
significant differences between the groups were found. Low expression was
observed in 95 percent of the goiter samples, showing significant differences
between neoplastic and non-neoplastic lesions. Furthermore, a significant result
was found with regard to the tumor size, with high HLA-E expression being related
to smaller tumors. Therefore, our data suggest that an increase in HLA-E may be
associated with the establishment of thyroid neoplasms, with either benign or
malignant features.
PMID- 24355225
TI - Decreased expression of protease inhibitor 9, a granzyme B inhibitor, in celiac
disease: a potential mechanism in enterocyte destruction and villous atrophy.
AB - The objective of this study was to assess the expression of protease inhibitor 9,
a granzyme B inhibitor, in human small intestine, and to evaluate its
cytoprotective role in the celiac disease of children. Twelve subjects with
untreated celiac disease and thirteen healthy controls were examined by
endoscopy. The expression of protease inhibitor 9 was analyzed
immunohistochemically from duodenal biopsies and compared to granzyme B
expression, apoptosis rate, number of intraepithelial lymphocytes and villus and
crypt height data from the biopsies. We discovered that protease inhibitor 9 is
expressed in the cytoplasm of the duodenal epithelial cells in the majority of
cases. The enterocyte expression of protease inhibitor 9 was lower in celiac
disease patients than in controls. Protease inhibitor 9 expression also showed a
negative correlation with the number of apoptotic cells, overall density of
granzyme B expressing intraepithelial lymphocytes, the height of the crypts and
the severity of villous atrophy in duodenum. Therefore, we conclude that the
protease inhibitor 9 is constantly expressed in the enterocytes of normal
duodenum and the expression is decreased in celiac disease. These findings
suggest that protease inhibitor 9 has a role in duodenal homeostasis and in the
protection of enterocytes from misdirected granzyme B. Indeed, observed
associations of lowered protease inhibitor 9 expression together with increased
granzyme B expression, apoptosis rate and severity of villous atrophy suggest
that impaired balance between granzyme B mediated cytotoxicity and its inhibition
by protease inhibitor 9 forms an important factor in the pathogenesis of villous
atrophy in celiac disease.
PMID- 24355226
TI - Cerebrospinal fluid T-regulatory cells recognize Borrelia burgdorferi NAPA in
chronic Lyme borreliosis.
AB - The NapA protein of B. burgdorferi is essential for the persistence of
spirochetes in ticks. One of the most intriguing aspects of NapA is its potential
to interfere with the host immune system. Here, we investigated the role of the
acquired immune responses induced by NapA in the cerebrospinal fluids (CSF) of
patients with chronic Lyme borreliosis. We evaluated the cytokine profile induced
in microglia cells and CSF T cells following NapA stimulation. We report here
that NapA induced a regulatory T (Treg) response in the CSF of patients with
chronic Lyme borreliosis and it is able to expand this suppressive response by
promoting the production of TGF-beta and IL-10 by microglia cells. Collectively,
these data strongly support a central role of NapA in promoting both Treg
response and immune suppression in the CSF of patients with chronic Lyme
borreliosis and suggest that NapA and the Treg pathway may represent novel
therapeutic targets for the prevention and treatment of the disease.
PMID- 24355227
TI - Mixed type I and type II collagen scaffold for cartilage repair: ultrastructural
study of synovial membrane response and healing potential versus microfractures
(a pilot study).
AB - The association between microfracture of the subchondral plate and a coverage
scaffold has emerged as a promising strategy to treat cartilage lesions in a one
step procedure. Between different types of scaffolds (e.g. collagen, hyaluronic
acid, polyglycolic acid) currently studied, type I collagen scaffold is the most
used for this purpose, and is currently adopted for humans. The aim of this study
was to test a novel scaffold made of mixed type I and II collagen (I-IICS) in
order to define the immunological reaction of the synovial tissue and the repair
capabilities induced by the collagen membrane when associated with microfracture.
Eight New Zealand White rabbits, aged 180 days, were operated on bilaterally on
the medial femoral condyle. A circular cartilage lesion was performed up to the
calcified layer of the medial femoral condyle, and the centre of the lesion was
microfractured. Randomly, one of the two lesions was covered with the I-IICS
(treated), and the other was left uncovered (control). The synovial membrane
reaction and the quality of the cartilage tissue repair were investigated at 2,
90, 180 and 270 days macroscopically, histomorphologically and ultrastructurally.
Expression of tumor necrosis factor-alpha (TNF-alpha) in synovial tissue by
immunocytochemistry analyses was also investigated. In the control group, at 2
days gold particles were localized mainly on synoviocyte type A, less on
synoviocytes type B and on collagen bundles; in the treated group the reaction is
more intense in cells in the matrix, but at 180 days controls and treated joints
were very similar. The synovial membranes of the joints receiving the I-IICS did
not reveal significant changes compared to the age-matched controls. Signs of
inflammation were present at the 90-day time-point, and became less evident at
afterwards. The degradation of the scaffolds was already evident at the 90-day
time-point. The quality of the cartilage repair of the rabbits treated with the I
IICS was slightly better in 5 cases out of 6 in comparison to the controls.
However, a statistically significant difference was not detected (p=0.06).
Scaffolds made of mixed type I and II collagen exhibited good biocompatibility
properties in vivo and favoured cartilage restoration when associated with
microfracture, as shown in this pilot study.
PMID- 24355228
TI - Periodontal bacteria in the genital tract: are they related to adverse pregnancy
outcome?
AB - One of the most important factors implicated in preterm birth (PTB) is acute
genitourinary tract infection. The bacteria causing chronic periodontal
inflammation include Gram-negative rods and anaerobes similar to those found in
women with bacterial vaginosis. The aim of this prospective study is to
investigate the relationship between oral and vaginal microflora and preterm low
birth weight. Real-time polymerase chain reaction was used to detect both the
presence and level of six periodontitis-related species: Aggregatibacter
actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia
(Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella
intermedia (Pi) for both oral samples of subgingival plaque and cervical samples,
obtained from 80 patients, during gynaecological examinations. The more
representative oral pathogen (less than 60 percent) species in oral samples of
preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women
presented periodontal pathogens in vaginal swab; the most representative species
with a percentage over 0.1 percent of total bacteria in genital tract of preterm
group were Tf, Td, and Piwith a positive correlation (less than 0.5). The
presence of the bacterium T. denticolain the vagina, regardless of the amount,
adversely affects preterm delivery.
PMID- 24355229
TI - Salso-sulphide thermal water in the prevention of recurrent respiratory
infections in children.
AB - Recurrent respiratory infections (RRI) represent a social problem for both the
pharmaco-economic impact and the burden on the family. Thermal water is popularly
well accepted. However, there is no scientific evidence of its preventive
activity on recurrent respiratory tract infections (RRI). Therefore, the purpose
of this study was to evaluate the effects of Agnano thermal water nasal
irrigation on RRI prevention in children.A total of 107 children (70 males, mean
age 4.5 plus minus1.2 years) with RRI were enrolled in the study. At baseline,
children were randomly assigned to the treatment with: A) inhaled crenotherapy
with salso-sulphide water or B) isotonic saline (NaCl 0.9 percent). Inhaled
therapy was performed using nasal washing by Rino-jet (ASEMA srl, Milan, Italy)
b.i.d. for 12 days. Nasal washing lasted 2 minutes per nostril. Immediately
before washing, children inhaled 1 l of water by stream inhalation per 2 minutes.
Crenotherapy was capable of significantly reducing: the number of respiratory
infections, nasal symptoms, neutrophil and bacteria count, turbinate and
adenoidal hypertrophy, presence of biofilm, and blockage of ostiomeatal complex
(OCM). In conclusion, this study provides the first evidence that Agnano
crenotherapy may be capable of preventing RRI in children as it exerts some
positive effects, such as reduction of nasal obstruction, OCM blockage, biofilm,
and inflammatory events.
PMID- 24355230
TI - Ink spot lentigo: singular clinical features in a case series of patients.
AB - Ink spot lentigo, also known as reticulated black solar lentigo, is a melanotic
macula commonly described in fair-skinned individuals on sun-exposed areas of the
body. Clinically it is a darkly pigmented type of solar lentigo; herein the term
ink spot lentigo. In contrast to common solar lentigines, ink spot lentigo is
reported as a unique lesion. However usually ink spot lentigo appears among
several common solar lentigines. We report a series of 5 patients who presented
ink spot lentigo with typical dermoscopic pattern but singular clinical features.
PMID- 24355231
TI - Clinically-irrelevant positivity for serum proteinase 3-ANCA in HIV disease.
AB - Diagnosis of small-vessel vasculitides (granulomatosis with polyangiitis,
microscopic polyangiitis, Churg-Strauss syndrome, and their localized forms) is
aided by the detection of serum antineutrophil cytoplasmic antibodies (ANCA).
However, serum ANCA positivity does not always mean vasculitis. Here, we report
on a 61-year-old female patient with very high serum levels of proteinase 3 ANCA,
marked hypergammaglobulinemia, low complement levels, and a 16-mm lung nodule on
chest CT scan, who was referred to our Institution with a provisional diagnosis
of possible granulomatosis with polyangiitis. On admission, history-taking
disclosed two recent episodes of viral reactivation (namely, cytomegalovirus and
Varicella-Zoster virus), while physical examination revealed lingual and nail
involvement suggestive of Candida infection. An immunodeficiency disorder was
eventually suspected. Search for antibodies against human immunodeficiency virus
(HIV) 1 and 2 turned positive. Western blot analysis confirmed HIV infection.
Thus, although ANCA detection may be helpful in diagnosing small-vessel
vasculitis in the appropriate clinical scenario, screening for HIV infection
should sometimes be considered to discriminate clinically irrelevant serum ANCA
positivity.
PMID- 24355232
TI - Anaesthesia management in patients with multiple chemical sensitivity syndrome.
AB - Multiple Chemical Sensitivity (MCS) is characterised by the appearance of
numerous and sometimes severe symptoms, when subjects are in contact with various
chemicals and medicinal substances. Currently there are no useful guidelines for
managing clinical issues and, specifically, anaesthesia for patients with MCS.
This case report describes anaesthesia management in a patient affected by
clinically documented MCS and a latex allergy, a candidate for a laparoscopic
cholecystectomy operation.
PMID- 24355233
TI - Preoperative assessment of salivary gland neoplasms with fine needle aspiration
cytology and echography: a retrospective analysis of 357 cases.
AB - Fine-needle aspiration cytology (FNAC) is a minimally invasive procedure usually
well tolerated, easy to perform, quick, cheap and easy to repeat in case of
doubts or non-diagnostic results. Echography is also a fast, cheap and non
invasive tool; however, the role of FNAC and echography in the diagnosis of
salivary gland pathology is not universally recognised. Three hundred and fifty
seven patients with a cytological diagnosis at FNAC, and 247 of these who were
also studied with echography, were enrolled for this retrospective study. The
final histopathological diagnoses, obtained after surgery, were then compared to
the preoperative FNAC diagnoses and echographic findings. From the analysis of
our data, the overall FNAC specificity resulted 93 percent, sensitivity 83
percent, and diagnostic accuracy 92 percent. Echography sensibility was 57.1
percent specificity 98.2 percent, while positive and negative predictive value
were respectively 80 percent and 94.8 percent. While echography can be useful in
order to provide a better characterization of salivary gland lesions, FNAC can
then be considered a safe diagnostic tool with reliable sensitivity and
specificity for the assessment of salivary gland pathology and thus for selecting
patients and indicating the best surgical treatment.
PMID- 24355234
TI - Pharmacological management of pediatric Kerion celsi.
AB - We report a case of severe tinea capitis, treated successfully with griseofulvin.
In our opinion, the treatment of this severe dermatophytosis with griseofulvin is
safe and effective. Other treatments, such as itraconazole pulsed therapy,
failed, despite an initial improvement, leading to an aggressive recurrence of
the lesion. We chose griseofulvin for its well-known large spectrum activity,
also against uncommon species, like Microsporum Gypseum, which are responsible
for the most severe cases.
PMID- 24355235
TI - Tanshinone VI inhibits the expression of intercellular adhesion molecule-1 and
vascular cell adhesion molecule-1.
AB - This study investigated the possible antitumor mechanisms of action of Tanshinone
VI, one of the components of Salvia miltiorrhiza Bunge, which is used in
traditional Chinese herbal medicine. To this end, the expression of intercellular
adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were
evaluated in-vitroin tumor necrosis factor-alpha (TNF-alpha)-stimulated
endothelial cells, with, or without the addition of Tanshinone VI (10, 20, 30, or
40 mM) in the culture medium; the effects of Tanshinone VI on angiogenesis was
also evaluated with an epithelial cell tube formation assay and its toxicity was
evaluated with a colorimetric (MTT) cell viability assay. The results showed that
the up-regulation of ICAM-1 and VCAM-1 induced by TNF-alpha was dose-dependently
inhibited by Tanshinone VI, with restoration of control levels at the dose of 40
mM; Tanshinone VI also had a remarkable anti-angiogenesis effect, already at the
dose of 10 mM, while none of the doses tested had significant effects on cell
viability. These results indicate that the antitumor properties of Tanshinone VI
can be ascribed to the inhibition of cell adhesion, due to blockage of the up
regulation of cell adhesion molecules, with the consequent inhibition of
metastases formation and/or angiogenesis. The lack of toxic effects at the dosage
used makes Tanshinone VI a good candidate for its therapeutic use in humans.
PMID- 24355236
TI - Latent virus reactivation risk and biological drugs: chronic inflammatory and
immune-mediated disorders.
AB - Psoriasis vulgaris, psoriatic arthritis and rheumatoid arthritis are chronic
inflammatory and immune-mediated disorders, widely distributed in the population
and induced by several environmental factors in genetically predisposed
individuals. Different therapies are currently used to treat these diseases.
Since these pathologies are characterized by an altered production of
proinflammatory cytokines and chemokines, and biological therapy is based on the
development of monoclonal antibodies or recombinant proteins against these
molecules, this therapy represents an important option. Nevertheless, it was
recently reported that biological agents have been associated with serious life
threatening infections. This article aims to summarize literature data on viral
reactivation risk that clinicians need to take into account when selecting the
most appropriate biological therapy for such patients.
PMID- 24355237
TI - Management of biofilm control in an elderly patient suffering from rheumatoid
arthritis: a case report.
AB - The increase in the average age of the population forces dentists and dental
hygienists to deal with clinical scenarios typical of the elderly. In old people
deep changes present both in systemic and oral health. These changes affect the
anatomical and functional integrity of many tissues, such as the mouth.
Impairment of patients' oral hygiene becomes manifested by local infections and
promotes the pathogenesis of periodontal diseases. There is also a significant
increase in autoimmune diseases, which are defined as disorders of the immune
system that result in abnormal immune responses. Among the autoimmune diseases of
medical interest we report a case of rheumatoid arthritis (RA) strictly related
to periodontal disease.
PMID- 24355238
TI - Hospitalization rates of complicated pneumococcal community-acquired pneumonia is
increasing in Tuscan children.
AB - To provide epidemiological data on community-acquired pneumonia (CAP) and
complicated CAP, a retrospective study was conducted on a partially vaccinated
paediatric population. Data from children hospitalized for CAP in Tuscan
hospitals between January 1st, 1999 and December 31st, 2009 were analysed. A
total of 5,450 children with CAP were hospitalized. Annual hospitalization rates
for CAP did not change significantly over the study period (X2 for trend= 0.652;
p=0.419). The total annual hospitalization rate for pneumococcal CAP varied
according to age (28.04 per 100,000 children aged less than 5 years, 10.06 per
100,000 children aged 6-12 years and 0.98 per 100,000 children aged greater
than13years). Hospitalization rates for pneumococcal CAP increased from12.84 (95
percent CI:7.35-18.34) in 2001 to 45.4 (95 percent CI:35.93-54.90) per 100,000
children aged less than 5 years in 2009 (p less than 0.0001). In addition, a
significant increase of hospitalization rates for complicated CAP (from 6.07 in
1999 to 13.66 in 2009 per 100,000 children; P less than 0.0001) and pneumococcal
complicated CAP (from 0.19 in 1999 to 3.41 in 2009 per 100,000 children) over the
study period were highlighted. Our epidemiological data confirm the decision to
introduce the PCV13 vaccine, to satisfy the need to prevent a wider group of
pneumococcal serotypes.
PMID- 24355239
TI - Doppler ultrasound study of penis in men with systemic sclerosis: a correlation
with Doppler indices of renal and digital arteries.
AB - Erectile dysfunction (ED) prevalence in male systemic sclerosis (SSc) is high and
its pathogenesis is unclear. The aim of the study is to assess correlation
between Doppler ultrasound indices of penis and kidneys or digital arteries in
male systemic sclerosis. Fourteen men with systemic sclerosis were enrolled in
this study. Erectile function was investigated by the International Index of
Erectile Function-5. Peak systolic velocity, end diastolic velocity, resistive
index, pulsative index, and systolic/diastolic ratio were measured on the
cavernous arteries at the peno-scrotal junction in the flaccid state, on the
interlobar artery of both kidneys and all ten proper palmar digital arteries. Ten
(71 percent) patients have an International Index of Erectile Function-5 less
than 21. Reduction of penis peak systolic velocity was observed in all SSc
subjects. Doppler indices of cavernous arteries correlate with the International
Index of Erectile Function-5. The renal and digital arteries resistive index
demonstrated a good correlation (p less than 0.0001) with International Index of
Erectile Function-5. A positive correlation exists between penis and kidney
arteries Doppler indices: end diastolic velocity (p less than 0.05, r=0.54),
resistive index (p less than 0.0001, r=0.90), systolic/diastolic ratio (p less
than 0.01, r=0.69). A positive correlation was observed between penis and digital
arteries Doppler indices: peak systolic velocity (p less than 0.01, r=0.68), end
diastolic velocity (p less than 0.01, r=0.75), resistive index (p less than
0.001, r=0.79), systolic/diastolic ratio (p less than 0.05, r=0.59). A
correlation exists between arterial impairment of penis and renal or digital
arteries.
PMID- 24355240
TI - Role of steroid therapy in pseudoxanthoma elasticum-like papillary dermal
elastolysis.
AB - Pseudoxanthoma Elasticum-like Papillary Dermal Elastolysis (PXE-PDE) is a
peculiar idiopathic elastolytic disorder that clinically resembles Psudoxanthoma
elasticum(PXE). It is histologically characterized by a total or partial loss of
elastic fibers in the papillary dermis. It more often affects elderly women and
is characterized by asymptomatic and symmetrical yellowish papules localized
predominantly on the neck, supraclavicular regions, and flexural areas. After
analyzing a series of cases and the recent literature suggesting that
glucocorticoids may down-regulate the elastin gene expression and elastin mRNA,
in cultured human skin fibroblasts, we think that high dose and prolonged steroid
therapy may contribute to the appearance of PXE-PDE lesions.
PMID- 24355241
TI - Intranasal administration of hyaluronan as a further resource in olfactory
performance in multiple chemical sensitivity syndrome.
AB - Multiple chemical sensitivity (MCS) is a relatively common clinical diagnosis in
western populations and its symptoms (i.e. dysosmia) are mainly triggered by
chemical compounds, such as common odorants. The aim of this study was to test
the effect of intranasal administration of hyaluronic acid (HA) on odour
threshold and related quality of life in MCS syndrome. Two randomized groups of
MCS patients received 30 days? administration of either a nasal spray
(Ialumar(r)) containing HA [HA group (HAG); n=29] or only physiological
solution[PS group (PG); n=30]. Both groups were investigated using the Sniffin?
Sticks test (SST) battery, Questionnaire of Olfactory Disorder (QOD) and Zung
Anxiety Scale (SAS) before randomization and after treatment. Paired t-test
analysis found a statistically significant reduction in odour threshold (OT) and
an improvement in QOD and SAS between pre- and post-treatment results only in the
HAG. Furthermore, positive correlations were found between the OT reduction, SAS
and QOD improvement. Thus, intranasal administration of HA could be suggested as
a further well-tolerated resource in alleviating MCS olfactory discomfort.
PMID- 24355242
TI - Combined clinical, capillaroscopic and ultrasound evaluation during treatment of
plaque psoriasis with oral cyclosporine.
AB - Imaging techniques have only recently been utilized in combination with clinical
observation to objectively quantify psoriasis severity and evaluate therapeutic
response. This study evaluated the sensitivity of videodermatoscopy (VD) and
ultrasound (US) imaging to assess the therapeutic effect of cyclosporine (Cs) in
patients with moderate-to-severe psoriasis. Twenty patients with moderate-to
severe psoriasis were divided into two groups (A and B) based on PASI score.
Group A (PASI greater than 16) was treated with 5 mg/Kg/day Cs for 4 weeks and
another 4 weeks with 3 mg/Kg/day Cs. Group B (PASI 10-16) received 3 mg/Kg/day Cs
for 8 weeks. A target plaque was selected for each subject and evaluated using a
Target Lesion Score (TLS) for erythema, scaling and degree of infiltration, in
addition to VD and US at baseline, 2, 4 and 8 weeks. At the end of the study,
improvement rate was quicker in group A vsgroup B after 8 weeks of Cs therapy.
All three parameters (TLS, VD and US) strongly correlated with one another. Skin
thickness was the first parameter that improved, followed by TLS. In contrast,
improvement in VD was delayed. Normalization rate of vascular pattern (assessed
by VD) was low in both groups but higher in group A vs group B (46 vs 22
percent), despite virtually complete normalization by clinical and US assessment.
In conclusion, while both TLS and US can be utilized in the evaluation of
therapeutic efficacy in patients with plaque psoriasis, VD can provide
information on vascular response to treatment, which may likely affect the
duration of therapy and the relapse rates.
PMID- 24355243
TI - Influence of alcohol on social anxiety: an investigation of attentional,
physiological and behavioral effects.
AB - Social anxiety disorder and alcohol use disorders are highly comorbid. It remains
unclear, however, if and how alcohol influences attentional processes and
physical symptoms in social anxiety. In a balanced-placebo-design, high and
normally socially anxious participants gave a speech while performing a task,
which simultaneously measures internal and external attention. Only high anxious
participants showed a preferential processing of external probes, which was
eliminated by alcohol or the mere expectation of drinking alcohol. Furthermore,
alcohol reduced facial blushing as well as self-reported social anxiety during
public speaking. Decreases in anxiety were significantly associated with a
reduction of the external focus in the high anxious group. Understanding alcohol
as a substance influencing cognitive processes as well as physiological symptoms
of anxiety further contributes to our understanding of alcohol use as a safety
behavior in social anxiety disorder.
PMID- 24355244
TI - The impact of cognitive control, incentives, and working memory load on the P3
responses of externalizing prisoners.
AB - The P3 amplitude reduction is one of the most common correlates of externalizing.
However, few studies have used experimental manipulations designed to challenge
different cognitive functions in order to clarify the processes that impact this
reduction. To examine factors moderating P3 amplitude in trait externalizing, we
administered an n-back task that manipulated cognitive control demands, working
memory load, and incentives to a sample of male offenders. Offenders with high
trait externalizing scores did not display a global reduction in P3 amplitude.
Rather, the negative association between trait externalizing and P3 amplitude was
specific to trials involving inhibition of a dominant response during infrequent
stimuli, in the context of low working memory load, and incentives for
performance. In addition, we discuss the potential implications of these findings
for externalizing-related psychopathologies. The results complement and expand
previous work on the process-level dysfunction contributing to externalizing
related deficits in P3.
PMID- 24355246
TI - Evaluating regional workshops on strengthening the capacity of healthcare
professional associations to achieve Millennium Development Goals 4 and 5.
AB - OBJECTIVE: In 2007-2008, the Partnership for Maternal, Newborn and Child Health
(PMNCH), Geneva, organized capacity-building workshops in Malawi, Burkina Faso,
and Bangladesh. Their aim was to strengthen the role of healthcare professional
associations (HCPAs) in national reproductive, maternal, newborn, and child
health (RMNCH) planning and programs. The present cross-sectional study evaluated
the outcomes of these regional workshops. METHODS: In 2010, a structured survey,
telephone interviews of workshop participants, and a document review were used to
analyze the impact of these workshops. RESULTS: Overall, HCPAs in only 2 of the
17 participating countries (11.8%) were able to increase their impact on RMNCH
planning. Although all countries developed action plans, 15 (88.2%) were unable
to fully implement them despite increased interactions among HCPAs and with the
Ministry of Health (MOH). Nine countries (52.9%) implemented their action plans
partly. Engagement of the MOH emerged as a strong indicator of HCPA contribution
toward RMNCH planning. CONCLUSION: Strong and sustained follow-up by PMNCH, a
clear sense of ownership by HCPAs, designated staff, and financial resources
emerged as important determinants for the implementation of action plans. These
workshops were generally successful in both encouraging HCPA collaboration and
marching toward Millennium Development Goals 4 and 5.
PMID- 24355247
TI - Natural product based leads to fight against leishmaniasis.
AB - The growing incidence of parasitic resistance against generic pentavalent
antimonials, specifically for visceral disease in Indian subcontinent, is a
serious issue in Leishmania control. Notwithstanding the two treatment
alternatives, that is amphotericin B and miltefosine are being effectively used
but their high cost and therapeutic complications limit their use in endemic
areas. In the absence of a vaccine candidate, identification, and
characterization of novel drugs and targets is a major requirement of leishmanial
research. This review describes current drug regimens, putative drug targets,
numerous natural products that have shown promising antileishmanial activity
alongwith some key issues and strategies for future research to control
leishmaniasis worldwide.
PMID- 24355245
TI - Epidemiologic and genetic characteristics of mumps viruses isolated in China from
1995 to 2010.
AB - The epidemiologic and genetic characteristics of mumps viruses detected in China
from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China
with a high overall incidence rate. The incidence of mumps in Western China was
higher than that in other regions of the country. Each year, most of mumps cases
occurred between April and July, but a small peak also occurred in November and
December. Mumps cases primarily affected the under 15 year old age group.
Virologic data demonstrated that genotype F was the predominant circulating
genotype throughout China for at least 15 years and no other genotype was
detected between 1995 and 2010. Analysis of sequence data from the small
hydrophobic (SH) gene indicated that multiple transmission chains of genotype F
were found in various provinces of China, with no apparent chronologic and
geographic restriction. This is the first report describing the epidemiology of
mumps and genetic characterization of mumps viruses at the national level in
China.
PMID- 24355248
TI - Resource use of low-income households--approach for defining a decent lifestyle?
AB - A decent, or sufficient, lifestyle is largely considered an important objective
in terms of a sustainable future. However, there can be strongly varying
definitions of what a decent lifestyle means. From a social sustainability point
of view, a decent lifestyle can be defined as the minimum level of consumption
ensuring an acceptable quality of life. From an ecological sustainability point
of view, a decent lifestyle can be defined as a lifestyle that does not exceed
the carrying capacity of nature in terms of natural resource use. The paper
presents results of a study on the natural resource use of 18 single households
belonging to the lowest income decile in Finland. The yearly "material footprint"
of each household was calculated on the basis of the data gathered in a
questionnaire and two interviews. The results show that the natural resource use
of the participating households was lower than the one of the average consumer.
Furthermore, 12 of 18 households had a smaller material footprint than the
"decent minimum" reference budget defined by a consumer panel. However, the
resource use of all the households and lifestyles studied is still higher than
long-term ecological sustainability would require. The paper concludes that the
material footprint is a suitable approach for defining and measuring a decent
lifestyle and provides valuable information on how to dematerialize societies
towards sustainability.
PMID- 24355249
TI - Electro-chemical arsenic remediation: field trials in West Bengal.
AB - Millions of people in rural South Asia are exposed to high levels of arsenic
through groundwater used for drinking. Many deployed arsenic remediation
technologies quickly fail because they are not maintained, repaired, accepted, or
affordable. It is therefore imperative that arsenic remediation technologies be
evaluated for their ability to perform within a sustainable and scalable business
model that addresses these challenges. We present field trial results of a 600 L
Electro-Chemical Arsenic Remediation (ECAR) reactor operating over 3.5 months in
West Bengal. These results are evaluated through the lens of a community scale
micro-utility business model as a potential sustainable and scalable safe water
solution for rural communities in South Asia. We demonstrate ECAR's ability to
consistently reduce arsenic concentrations of ~266 MUg/L to <5 MUg/L in real
groundwater, simultaneously meeting the international standards for iron and
aluminum in drinking water. ECAR operating costs (amortized capital plus
consumables) are estimated as $0.83-$1.04/m(3) under realistic conditions. We
discuss the implications of these results against the constraints of a
sustainable and scalable business model to argue that ECAR is a promising
technology to help provide a clean water solution in arsenic-affected areas of
South Asia.
PMID- 24355252
TI - Deriving the colloidal synthesis of crystalline nanosheets to create self
assembly monolayers of nanoclusters.
AB - Two-dimensional (2D) nanomaterials with the thickness at atomic level are
promising candidates for a wide range of applications, and now reach the point to
create diversified 2D architectures. The colloidal synthesis route is powerful to
produce crystalline nanosheets, nanoribbons and nanoplatelets, and the self
assembly strategy is robust to integrate the functionalities of different nano
objects. In this review, we bridge the colloidal synthesis of nanosheets and the
2D self-assembly of nanoclusters (NCs) with the aim to further optimize the
physical and chemical properties of 2D nanomaterials. Ultrasmall NCs, the
intermediate for synthesizing nanosheets, are highlighted to show the similarity
of 2D crystallization and 2D self-assembly. The modification of conventional 2D
colloidal synthesis route greatly permits the controlled self-assembly of NCs
into free-standing monolayers in colloidal solutions.
PMID- 24355250
TI - Investigation of temporal and spatial variations in atmospheric concentrations of
PCDDs and PCDFs in Istanbul.
AB - In this study, temporal and spatial variations of the atmospheric concentrations
of polychlorinated-p-dibenzo dioxin (PCDDs) and polychlorinated dibenzofuran
(PCDFs) congeners were investigated in Istanbul at three different locations. The
highest average concentration (3481 fg/m(3)) was observed at the sampling
location which is characterized by mixed source groups during colder months. The
lowest average concentration (749 fg/m(3)) was observed at sampling station which
is characterized by semi-urban characteristics. ?PCDD/F concentration showed
seasonal variation in this study. The highest average concentration was
determined to be 4373 fg/m(3) in winter while the lowest average concentration
was determined to be 498 fg/m(3) in summer.
PMID- 24355253
TI - The Block Relevance (BR) analysis supports the dominating effect of solutes
hydrogen bond acidity on DeltalogP(oct-tol).
AB - The role of hydrogen bond acidity, i.e., the ability of chemicals to act as
hydrogen bond donors (HBD), is a crucial element in pharmaceutical sciences and
medicinal chemistry. It has been shown that the difference between logP values
(DeltalogP) obtained in two different biphasic systems is informative of the
solutes HBD properties and thus useful in the prediction of drugs human fate. In
this study, we collected from literature more than 200 experimental logPtol (the
logarithm of the partition coefficient P in the toluene/water system) values
along with their corresponding logPoct (the logarithm of the partition
coefficient P in the octanol/water system) values. The dataset was processed
using a purposely-built in-house software to remove molecules that are
potentially able to form IMHBs. On the remaining structures the DeltalogPoct-tol
(=logPoct - logPtol) have been calculated and correlated with 82
VolSurf+descriptors through a PLS model. Finally the Block Relevance (BR)
analysis has been used to group the descriptors in six easy-to-interpret blocks
and to show graphically the relevance of a certain block in the PLS model. BR
analysis showed that the hydrogen bond donor (HBD) properties of the solutes
mainly govern DeltalogPoct-tol. This supports the use of DeltalogPoct-tol to
estimate HBD properties of solutes and its role in the intramolecular hydrogen
bonding (IMHB) interpretation scheme recently reported in the literature.
PMID- 24355254
TI - Are other fluorescent tags used instead of ethidium bromide safer?
AB - Ethidium bromide (EtBr) is a well-known fluorescent tag usually applied in
molecular biological techniques like agarose gel electrophoresis. The mechanism
of action for such compounds is known, in which these compounds are able to bind
to the kinetoplastid DNA and to alter their conformation to Z-DNA molecules that
stop replication of kinetoplastid DNA leading to Trypanosoma death. Although the
usual amounts used in laboratories are considered as below the level required to
cause toxicity (LD50 in oral administration in rat is 1.5 g/Kg), the mentioned
concentrations are high enough to involve in replication of mitochondrial DNA in
some human cell lines. Regarding the points that EtBr is very stable in the
environment and if degraded especially by use of bleaches that result in
formation of mutagenic compounds, there is a big concern about its use. Although
application of EtBr is going to be restricted and replaced with other tags such
as SYBR(r) products, the safety of the new substituted compounds are still in
doubt and except a few data, there is no essential evidence available to confirm
that they are safer than EtBr. Further investigations are recommended to compare
their relative biosafety hazards.
PMID- 24355255
TI - A comparison of variable angle versus fixed angle distal femoral resection in
primary total knee arthroplasty.
AB - This study assessed whether using a variable distal valgus resection angle
improved post-operative coronal lower limb alignment in total knee arthroplasty
(TKA). Two groups were compared: Fixed (n = 124), where a fixed distal valgus
resection angle of 7 degrees was used; Variable (n = 87), where the resection
angle was adjusted to the measured femoral mechanical anatomical (FMA) angle of
the patient. FMA and mechanical femoro-tibial (MFT) angles were measured on pre
operative and post-operative hip-knee-ankle radiographs. 85% of patients in the
Variable group had a post-operative MFT angle within 0 degrees +/- 3 degrees
compared to 69% in the Fixed group (P = 0.006). The use of a fixed distal femoral
resection angle for all patients is not appropriate. Setting the resection to an
individual patient's FMA angle can significantly improve the post-operative MFT
angle.
PMID- 24355256
TI - Perioperative antibiotics.
PMID- 24355257
TI - Cementless total knee arthroplasty in obese patients: a prospective matched study
with follow-up of 5-10 years.
AB - A prospective matched cohort study was performed to compare outcomes of
cementless total knee arthroplasties between 171 knees in obese patients (BMI >=
30) and 171 non-obese patients (BMI < 30). Mean follow-up was 7 years. There were
no significant differences in overall functional outcomes or components
alignment. In the obese group, there were 14 perioperative complications, 9
revisions, and 5 other patients were considered clinical failures, whereas in the
non-obese group there were 3, 5, and 7, respectively. There were no significant
differences between obese class I-II and class III (morbid) subgroups. The obese
and non-obese groups had similar implant survivorship at 7 years. Although TKA
outcome in obese was satisfactory, these patients should be informed of the
perioperative risks, and advised to lose weight prior to surgery.
PMID- 24355258
TI - Urinary biomarkers for the early diagnosis of retinopathy and nephropathy in type
1 diabetes mellitus: a "steady stream" of information using proteomics.
PMID- 24355260
TI - Thoracic tumor effects on plasmatic coagulation: role of hemeoxygenase-1.
AB - OBJECTIVES: Lung cancer is an important health threat worldwide, and is
associated with a 3.8-13.9% incidence of thrombophilia. Of interest, patients
with lung tumors have been noted to have an increase in endogenous carbon
monoxide production via upregulation of hemeoxygenase-1 activity. Given that it
has been demonstrated that carbon monoxide enhances plasmatic coagulation in
vitro and in vivo via formation of carboxyhemefibrinogen, we sought to determine
if patients with thoracic tumors undergoing lung resection/pneumonectomy had an
increase in endogenous carbon monoxide and concurrent plasmatic
hypercoagulability. MATERIALS AND METHODS: Nonsmoking patients with thoracic
tumors (n=19) had preoperative carboxyhemoglobin (a measure of carbon monoxide
production) determined, and a thromboelastometric method to assess citrated
plasma coagulation kinetics and the formation of carboxyhemefibrinogen was
utilized. Thoracic tumor patient coagulation kinetics was compared with normal
subject (n=30) plasma samples. RESULTS AND CONCLUSION: Patients with thoracic
tumors were determined to have an abnormally increased carboxyhemoglobin
concentration of 2.1+/-0.6%, indicative of hemeoxygenase-1 upregulation. It was
found that 84% of thoracic tumor patients had plasma clot strength that exceeded
the 95% confidence interval value observed in normal subjects, and 44% of this
hypercoagulable subgroup had carboxyhemefibrinogen formation. Future
investigation of the role played by plasmatic hypercoagulability and
hemeoxygenase-1 derived carboxyhemefibrinogen in the pathogenesis of thoracic
tumor related thrombophilia is warranted.
PMID- 24355259
TI - NF-kappaB protein expression associates with (18)F-FDG PET tumor uptake in non
small cell lung cancer: a radiogenomics validation study to understand tumor
metabolism.
AB - INTRODUCTION: We previously demonstrated that NF-kappaB may be associated with
(18)F-FDG PET uptake and patient prognosis using radiogenomics in patients with
non-small cell lung cancer (NSCLC). To validate these results, we assessed NF
kappaB protein expression in an extended cohort of NSCLC patients. METHODS: We
examined NF-kappaBp65 by immunohistochemistry (IHC) using a Tissue Microarray.
Staining intensity was assessed by qualitative ordinal scoring and compared to
tumor FDG uptake (SUVmax and SUVmean), lactate dehydrogenase A (LDHA) expression
(as a positive control) and outcome using ANOVA, Kaplan Meier (KM), and Cox
proportional hazards (CPH) analysis. RESULTS: 365 tumors from 355 patients with
long-term follow-up were analyzed. The average age for patients was 67+/-11
years, 46% were male and 67% were ever smokers. Stage I and II patients comprised
83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET
scans available, average SUVmax and SUVmean were 8.3+/-6.6, and 3.7+/-2.4
respectively. Increasing NF-kappaBp65 expression, but not LDHA expression, was
associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF
kappaBp65 and positive FDG uptake were significantly associated with more
advanced stage, tumor histology and invasion. Higher NF-kappaBp65 expression was
associated with death by KM analysis (p=0.06) while LDHA was strongly associated
with recurrence (p=0.04). Increased levels of combined NF-kappaBp65 and LDHA
expression were synergistic and associated with both recurrence (p=0.04) and
death (p=0.03). CONCLUSIONS: NF-kappaB IHC was a modest biomarker of prognosis
that associated with tumor glucose metabolism on FDG PET when compared to
existing molecular correlates like LDHA, which was synergistic with NF-kappaB for
outcome. These findings recapitulate radiogenomics profiles previously reported
by our group and provide a methodology for studying tumor biology using
computational approaches.
PMID- 24355261
TI - Correlative cryogenic tomography of cells using light and soft x-rays.
AB - Correlated imaging is the process of imaging a specimen with two complementary
modalities, and then combining the two data sets to create a highly informative,
composite view. A recent implementation of this concept has been the combination
of soft x-ray tomography (SXT) with fluorescence cryogenic microscopy (FCM). SXT
FCM is used to visualize cells that are held in a near-native, cryopreserved. The
resultant images are, therefore, highly representative of both the cellular
architecture and molecular organization in vivo. SXT quantitatively visualizes
the cell and sub-cellular structures; FCM images the spatial distribution of
fluorescently labeled molecules. Here, we review the characteristics of SXT-FCM,
and briefly discuss how this method compares with existing correlative imaging
techniques. We also describe how the incorporation of a cryo-rotation stage into
a cryogenic fluorescence microscope allows acquisition of fluorescence cryogenic
tomography (FCT) data. FCT is optimally suited for correlation with SXT, since
both techniques image the specimen in 3-D, potentially with similar, isotropic
spatial resolution.
PMID- 24355262
TI - Biological nitrate removal processes from drinking water supply-a review.
AB - This paper reviews both heterotrophic and autotrophic processes for the removal
of nitrate from water supplies. The most commonly used carbon sources in
heterotrophic denitrification are methanol, ethanol and acetic acid. Process
performance for each feed stock is compared with particular reference nitrate and
nitrite residual and to toxicity potential. Autotrophic nitrate removal has the
advantages of not requiring an organic carbon source; however the slow growth
rate of autotrophic bacteria and low nitrate removal rate have contributed to the
fact that relatively few full scale plants are in operation at the present time.
PMID- 24355263
TI - Development, reliability, and validity of a novel Epidermolysis Bullosa Disease
Activity and Scarring Index (EBDASI).
AB - BACKGROUND: There is a lack of validated standardized outcome measures for
epidermolysis bullosa (EB) that can separate activity from damage. OBJECTIVE: We
sought to develop and validate an instrument for inherited EB of all ages and
subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores
activity responsive to therapy separately from scarring. METHODS: The EBDASI was
validated by comparing its reliability and validity against the Birmingham EB
Severity (BEBS) score (partially validated with activity mixed with scarring),
using the Physician Global Assessment (PGA) scale as a reference measurement.
Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2
junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using
the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad
hoc basis during routine patient clinic were also included. RESULTS: For
interrater reliability, the overall total score intraclass correlation
coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS
0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the
intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926
(0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation
with PGA (rho = 0.871) than BEBS with PGA (rho = 0.852). Intraclass correlation
coefficients scatterplots showed the EBDASI was better at distinguishing milder
forms of EB, with better correlations at higher severity scores than the BEBS.
LIMITATIONS: A limited number of patients were recruited for this study. An
independent study will be required to demonstrate the responsiveness of the
EBDASI. CONCLUSION: The EBDASI demonstrated excellent reliability and validity,
as compared with 2 other outcome measures.
PMID- 24355264
TI - Clinical and cytologic features of antibiotic-resistant acute paronychia.
AB - BACKGROUND: Acute paronychia usually is treated as a bacterial infection, but
antibiotic-resistant acute paronychia may be caused by other infectious and
noninfectious problems. OBJECTIVE: We sought to describe the clinical, etiologic,
cytologic, and therapeutic features of antibiotic-resistant acute paronychia.
METHODS: A retrospective review of medical records and cytology was performed in
58 patients (age, 1 month-91 years; 36 children and adolescents [62%] and 22
adults [38%]) who had antibiotic-resistant acute paronychias. RESULTS: Causes of
paronychia included bacteria (25 patients [43%]), viruses (21 patients [36%]),
fungi (5 patients [9%]), drugs (3 patients [5%]), pemphigus vulgaris (3 patients
[5%]), and trauma (1 patient [2%]). Diagnostic cytologic findings were noted in
54 patients (93%); no diagnostic cytologic findings were present with drug
induced (3 patients) or traumatic (1 patient) paronychia. The most common
predisposing factors were the habits of finger- or thumb-sucking (14 patients
[24%]) and nail-biting (11 patients [19%]). Complications included id reaction
with erythema multiforme in 3 patients (5%). LIMITATIONS: Limitations include
retrospective study design from 1 treatment center. CONCLUSION: Antibiotic
resistant acute paronychia may be infectious or noninfectious. Cytologic
examination with Tzanck smear may be useful diagnostically and may prevent
unnecessary use of antibiotics and surgical drainage.
PMID- 24355265
TI - Aspirin use and melanoma risk: a review of the literature.
AB - In view of the increasing incidence of melanoma, it is critical to find effective
preventive approaches. Contradictory evidence has been reported with regard to
the possible association of aspirin use and the risk of melanoma. We review these
studies and seek to elucidate the mechanism by which aspirin may produce a
chemoprotective effect against melanoma.
PMID- 24355266
TI - Sunlight is the best disinfectant: legal and ethical analysis of a Mohs referral
gone awry.
PMID- 24355267
TI - Reply to: Pityriasis rosea and pityriasis rosea-like eruptions.
PMID- 24355268
TI - Pityriasis rosea and pityriasis rosea-like eruptions.
PMID- 24355269
TI - Letter to the editor.
PMID- 24355270
TI - Pityriasis rosea and activation of latent herpesvirus infections.
PMID- 24355271
TI - Predictors of thick and lethal melanoma in white young adults in the United
States.
PMID- 24355272
TI - Reply: To PMID 23317980.
PMID- 24355273
TI - IgA pemphigus: case series with emphasis on therapeutic response.
PMID- 24355274
TI - Primary nonadherence (failure to obtain prescribed medicines) among dermatology
patients.
PMID- 24355275
TI - Diabetic foot ulcers: Part I. Pathophysiology and prevention.
AB - Diabetes mellitus is a serious, life-long condition that is the sixth leading
cause of death in North America. Dermatologists frequently encounter patients
with diabetes mellitus. Up to 25% of patients with diabetes mellitus will develop
diabetic foot ulcers. Foot ulcer patients have an increased risk of amputation
and increased mortality rate. The high-risk diabetic foot can be identified with
a simplified screening, and subsequent foot ulcers can be prevented. Early
recognition of the high-risk foot and timely treatment will save legs and improve
patients' quality of life. Peripheral arterial disease, neuropathy, deformity,
previous amputation, and infection are the main factors contributing to the
development of diabetic foot ulcers. Early recognition of the high-risk foot is
imperative to decrease the rates of mortality and morbidity. An interprofessional
approach (ie, physicians, nurses, and foot care specialists) is often needed to
support patients' needs.
PMID- 24355276
TI - Diabetic foot ulcers: Part II. Management.
AB - The management of diabetic foot ulcers can be optimized by using an
interdisciplinary team approach addressing the correctable risk factors (ie, poor
vascular supply, infection control and treatment, and plantar pressure
redistribution) along with optimizing local wound care. Dermatologists can
initiate diabetic foot care. The first step is recognizing that a loss of skin
integrity (ie, a callus, blister, or ulcer) considerably increases the risk of
preventable amputations. A holistic approach to wound assessment is required.
Early detection and effective management of these ulcers can reduce
complications, including preventable amputations and possible mortality.
PMID- 24355278
TI - Rapidly growing nodule on the cheek of a 12-year-old boy.
PMID- 24355279
TI - The introduction of skin self-photography as a supplement to skin self
examination for the detection of skin cancer.
PMID- 24355280
TI - Acute transverse myelitis during treatment with etanercept for severe plaque
psoriasis.
PMID- 24355281
TI - Ostomy associated cutaneous colonic metaplasia.
PMID- 24355282
TI - Hypersensitivity to romidepsin.
PMID- 24355284
TI - Dermoscopy of acral fibromyxoma.
PMID- 24355285
TI - Macular eruption revealing hypomelanotic cutaneous melanoma metastases:
diagnostic role of dermoscopy.
PMID- 24355286
TI - Lysis of Chlamydomonas reinhardtii by high-intensity focused ultrasound as a
function of exposure time.
AB - Efficient lysis of microalgae for lipid extraction is an important concern when
processing biofuels. Historically, ultrasound frequencies in the range of 10-40
kHz have been utilized for this task. However, greater efficiencies might be
achievable if higher frequencies could be used. In our study, we evaluated the
potential of using 1.1 MHz ultrasound to lyse microalgae for biofuel production
while using Chlamydomonas reinhardtii as a model organism. The ultrasound was
generated using a spherically focused transducer with a focal length of 6.34 cm
and an active diameter of 6.36 cm driven by 20 cycle sine-wave tone bursts at a
pulse repetition frequency of 2 kHz (3.6% duty cycle). The time-average acoustic
power output was 26.2 W while the spatial-peak-pulse-average intensity (ISPPA)
for each tone burst was 41 kW/cm(2). The peak compressional and rarefactional
pressures at the focus were 102 and 17 MPa, respectively. The exposure time was
varied for the different cases in the experiments from 5s to 9 min and cell lysis
was assessed by quantifying the percentage of protein and chlorophyll release
into the supernate as well as the lipid extractability. Free radical generation
and lipid oxidation for the different ultrasound exposures were also determined.
We found that there was a statistically significant increase in lipid
extractability for all of the exposures compared to the control. The longer
exposures also completely fragmented the cells releasing almost all of the
protein and chlorophyll into the supernate. The cavitation activity did not
significantly increase lipid oxidation while there was a minor trend of increased
free radical production with increased ultrasound exposure.
PMID- 24355287
TI - Simulation of the spatial distribution of the acoustic pressure in sonochemical
reactors with numerical methods: a review.
AB - Numerical methods for the calculation of the acoustic field inside sonoreactors
have rapidly emerged in the last 15 years. This paper summarizes some of the most
important works on this topic presented in the past, along with the diverse
numerical works that have been published since then, reviewing the state of the
art from a qualitative point of view. In this sense, we illustrate and discuss
some of the models recently developed by the scientific community to deal with
some of the complex events that take place in a sonochemical reactor such as the
vibration of the reactor walls and the nonlinear phenomena inherent to the
presence of ultrasonic cavitation. In addition, we point out some of the upcoming
challenges that must be addressed in order to develop a reliable tool for the
proper designing of efficient sonoreactors and the scale-up of sonochemical
processes.
PMID- 24355288
TI - Photodegradation of iodinated trihalomethanes in aqueous solution by UV 254
irradiation.
AB - Photodegradation of 6 iodinated trihalomethanes (ITHMs) under UV irradiation at
254 nm was investigated in this study. ITHMs underwent a rapid photodegradation
process through cleavage of carbon-halogen bond with first-order rate constants
in the range of 0.1-0.6 min(-1). The effects of matrix species including nitrate,
humic acid (HA), bicarbonate, sulfate, and chloride were evaluated. The
degradation rate increased slightly in the presence of nitrate possibly due to
generation of HO at a low quantum yield via direct photolysis of nitrate, while
HA lowered the photodegradation rate of ITHMs due to its competitive UV
absorption. Moreover, bicarbonate, sulfate, and chloride had no significant
effect on photodegradation kinetics, as there is no UV absorption for these 3
species. In the study using surface water, treated water, and secondary effluent
from a wastewater treatment plant, high turbidity and natural organic matters
present in the water inhibited the photodegradation of ITHMs. The degradation
rates of 6 ITHMs in UV/H2O2 system were rather comparable and significantly
higher than those achieved in the UV system without H2O2. To develop a
quantitative structure-reactivity relationship (QSAR) model, the logarithm of
measured first-order rate constants was correlated with a number of molecular
descriptors. The best correlation was obtained with a combination of 3 molecular
descriptors, namely the bond strength of carbon-halogen to be broken in the rate
determining step, steric and electronic effects of all substituents to the carbon
center.
PMID- 24355289
TI - Modeling the sustainability of a ceramic water filter intervention.
AB - Ceramic water filters (CWFs) are a point-of-use water treatment technology that
has shown promise in preventing early childhood diarrhea (ECD) in resource
limited settings. Despite this promise, some researchers have questioned their
ability to reduce ECD incidences over the long term since most effectiveness
trials conducted to date are less than one year in duration limiting their
ability to assess long-term sustainability factors. Most trials also suffer from
lack of blinding making them potentially biased. This study uses an agent-based
model (ABM) to explore factors related to the long-term sustainability of CWFs in
preventing ECD and was based on a three year longitudinal field study. Factors
such as filter user compliance, microbial removal effectiveness, filter cleaning
and compliance declines were explored. Modeled results indicate that broadly
defined human behaviors like compliance and declining microbial effectiveness due
to improper maintenance are primary drivers of the outcome metrics of household
drinking water quality and ECD rates. The model predicts that a ceramic filter
intervention can reduce ECD incidence amongst under two year old children by
41.3%. However, after three years, the average filter is almost entirely
ineffective at reducing ECD incidence due to declining filter microbial removal
effectiveness resulting from improper maintenance. The model predicts very low
ECD rates are possible if compliance rates are 80-90%, filter log reduction
efficiency is 3 or greater and there are minimal long-term compliance declines.
Cleaning filters at least once every 4 months makes it more likely to achieve
very low ECD rates as does the availability of replacement filters for purchase.
These results help to understand the heterogeneity seen in previous intervention
control trials and reemphasize the need for researchers to accurately measure
confounding variables and ensure that field trials are at least 2-3 years in
duration. In summary, the CWF can be a highly effective tool in the fight against
ECD, but every effort should be made by implementing agencies to ensure
consistent use and maintenance.
PMID- 24355290
TI - Assessment of the application of bioanalytical tools as surrogate measure of
chemical contaminants in recycled water.
AB - The growing use of recycled water in large urban centres requires comprehensive
public health risk assessment and management, an important aspect of which is the
assessment and management of residual trace chemical substances. Bioanalytical
methods such as in vitro bioassays may be ideal screening tools that can detect a
wide range of contaminants based on their biological effect. In this study, we
applied thirteen in vitro assays selected explicitly for their ability to detect
molecular and cellular effects relevant to potential chemical exposure via
drinking water as a means of screening for chemical contaminants from recycled
water at 9 Australian water reclamation plants, in parallel to more targeted
direct chemical analysis of 39 priority compounds. The selected assays provided
measures of primary non-specific (cytotoxicity to various cell types), specific
(inhibition of acetylcholinesterase and endocrine receptor-mediated effects) and
reactive toxicity (mutagenicity and genotoxicity), as well as markers of adaptive
stress response (modulation of cytokine production) and xenobiotic metabolism
(liver enzyme induction). Chemical and bioassay analyses were in agreement and
complementary to each other: the results show that source water (treated
wastewater) contained high levels of biologically active compounds, with positive
results in almost all bioassays. The quality of the product water (reclaimed
water) was only marginally better after ultrafiltration or dissolved air
floatation/filtration, but greatly improved after reverse osmosis often reducing
biological activity to below detection limit. The bioassays were able to detect
activity at concentrations below current chemical method detection limits and
provided a sum measure of all biologically active compounds for that bioassay,
thus providing an additional degree of confidence in water quality.
PMID- 24355291
TI - Successful application of nitritation/anammox to wastewater with elevated organic
carbon to ammonia ratios.
AB - The nitritation/anammox process has been mainly applied to high-strength
nitrogenous wastewaters with very low biodegradable organic carbon content (<0.5
g COD?g N(-1)). However, several wastewaters have biodegradable organic carbon to
nitrogen (COD/N) ratios between 0.5 and 1.7 g COD?g N(-1) and thus, contain
elevated amounts of organic carbon but not enough for heterotrophic
denitrification. In this study, the influence of elevated COD/N ratios was
studied on a nitritation/anammox process with suspended sludge. In a step-wise
manner, the influent COD/N ratio was increased to 1.4 g COD?g N(-1) by
supplementing digester supernatant with acetate. The increasing availability of
COD led to an increase of the nitrogen removal efficiency from around 85% with
pure digester supernatant to >95% with added acetate while the nitrogen
elimination rate stayed constant (275 +/- 40 mg N?L(-1)?d(-1)). Anammox activity
and abundance of anammox bacteria (AMX) were strongly correlated, and with
increasing influent COD/N ratio both decreased steadily. At the same time,
heterotrophic denitrification with nitrite and the activity of ammonia oxidising
bacteria (AOB) gradually increased. Simultaneously, the sludge retention time
(SRT) decreased significantly with increasing COD loading to about 15 d and
reached critical values for the slowly growing AMX. When the SRT was increased by
reducing biomass loss with the effluent, AMX activity and abundance started to
rise again, while the AOB activity remained unaltered. Fluorescent in-situ
hybridisation (FISH) showed that the initial AMX community shifted within only 40
d from a mixed AMX community to "Candidatus Brocadia fulgida" as the dominant AMX
type with an influent COD/N ratio of 0.8 g COD?g N(-1) and higher. "Ca. Brocadia
fulgida" is known to oxidise acetate, and its ability to outcompete other types
of AMX indicates that AMX participated in acetate oxidation. In a later phase,
glucose was added to the influent instead of acetate. The new substrate
composition did not significantly influence the nitrogen removal nor the AMX
activity, and "Ca. Brocadia fulgida" remained the dominant type of AMX. Overall,
this study showed that AMX can coexist with heterotrophic bacteria at elevated
influent COD/N ratios if a sufficiently high SRT is maintained.
PMID- 24355292
TI - Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out
induce different pathological responses in the heart of male and female mice.
AB - AIMS: The nitric oxide and endothelin systems are key components of a local
paracrine hormone network in the heart. We previously reported that diastolic
dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS
/-) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have
been reported in both ET-1 and NO systems. Particularly, eNOS-/- mice present sex
related phenotypic differences. MAIN METHODS: We used the ET-1 transgenic
(ET+/+), eNOS-/-, and crossbred ET+/+eNOS-/- mice, and wild type controls. We
measured cardiac function by heart catheterization. Cardiac ventricles were
collected for histological and molecular profiling. KEY FINDINGS: We report here
that (i) the level of ET-1 expression in eNOS-/- mice was elevated in males but
not in females. (ii) Left ventricular end-diastolic blood pressure was higher in
male eNOS-/- mice than in females. (ii) eNOS-/- males but not females developed
cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intracardiac arteries
developed in female ET+/+ and eNOS-/- mice but not in males. Additionally, (v)
the cardiac expression of metalloprotease-9 was higher in eNOS-/- males compared
to females. Finally, (vi) cardiac proteome analysis revealed that the protein
abundance of the oxidative stress related enzyme superoxide dismutase presented
with sexual dimorphism in eNOS-/- and ET+/+ mice. SIGNIFICANCE: These results
indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout
mice are sex specific. Since both systems are key players in the pathogenesis of
cardiovascular diseases, our findings might be important in the context of gender
differences in patients with such diseases.
PMID- 24355293
TI - Antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H
Pyrazole-3-carbohydrazide, a new heterocyclic pyrazole derivative.
AB - AIMS: Heterocyclic pyrazole derivative has been described for the treatment of
pain and inflammatory diseases. This study evaluated the in vivo,
antinociceptive, anti-inflammatory and antipyretic effects of 1.5-diphenyl-1H
Pyrazole-3-carbohydrazide (1.5-DHP) and the in vivo or in vitro mechanism of
action. MAIN METHODS: Acetic acid-induced writhing, hot-plate and formalin
induced nociception tests were used to evaluate the antinociceptive effect, while
the rota-rod test was used to assess the motor activity. Croton oil-induced ear
edema and carrageenan-induced peritonitis tests were used to investigate the anti
inflammatory effect of 1.5-DHP. The antipyretic effect was assessed using the LPS
induced fever model. The mechanism of action was evaluated by PGE2 and TNF-alpha
measurement and cyclooxygenase inhibition assay. KEY FINDINGS: Oral
administration (p.o.) of 1.5-DHP (1, 3, 10 mg/kg) caused a dose-related
inhibition of the acetic acid-induced writhing, however the highest dose was not
effective on the hot-plate and rota-rod. In the formalin-induced nociception, 1.5
DHP (10mg/kg, p.o.) inhibited only the late phase of nociception. This same dose
of 1.5-DHP also reduced the croton oil-induced ear edema. 1.5-DHP (3, 10, 30
mg/kg, p.o.) produced a dose-related reduction of leukocyte migration on the
carrageenan-induced peritonitis. 1.5-DHP (60 mg/kg, p.o.) reduced the fever and
the increase of PGE2 concentration in the cerebrospinal fluid induced by LPS. 1.5
DHP inhibited both COXs in vitro. Finally, 1.5-DHP (10 mg/kg, p.o.) reduced the
TNF-alpha concentration in peritoneal exudates after carrageenan injection.
SIGNIFICANCE: These results indicate that 1.5-DHP produces anti-inflammatory,
antinociceptive and antipyretic effects by PGE2 synthesis reduction through COX
1/COX-2 inhibition and by TNF-alpha synthesis/release inhibition.
PMID- 24355294
TI - Ascorbic acid reverses the prolonged anesthetic action of pentobarbital in Akr1a
knockout mice.
AB - AIMS: Aldehyde reductase (AKR1A), a member of the aldo-keto reductase
superfamily, is highly expressed in the liver and is involved in both the
detoxification of carbonyl compounds and ascorbic acid biosynthesis. By
comparison with wild-type mice, Akr1a-knockout (Akr1a(-/-)) mice and human Akrla
transgenic (Akr1a(tg/+)) mice experience different anesthetic actions from
pentobarbital-prolonged in Akr1a-knockout (Akr1a(-/-)) mice and shortened in
human Akrla-transgenic (Akr1a(tg/+)) mice. MAIN METHODS: We investigated this
alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically
modified mice. KEY FINDINGS: Neither the cytosolic protein of wild-type mouse
liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid
administration neutralized the prolonged duration of the loss of the righting
reflex (LORR) in Akr1a(-/-) mice, but preincubation of pentobarbital with
ascorbic acid prior to administration did not change the anesthetic effect. Those
results indicated that ascorbic acid does not directly reduce pentobarbital.
Enzymatic activities and levels of the proteins of some cytochrome P450s that
make up a potent detoxification system for pentobarbital showed no changes in the
genetically modified mice examined. Thus, ascorbic acid also had no effect on the
detoxification system in the liver. The prolonged duration of LORR in the Akr1a(
/-) mice caused by pentobarbital and the neutralization of the anesthetic effect
by ascorbic acid together with other results imply that ascorbic acid alters the
responses of the neuronal system to anesthetics. SIGNIFICANCE: Pentobarbital
action is increased under conditions of ascorbic acid deficiency, and this may
have to be taken into account when anesthetizing malnourished patients.
PMID- 24355295
TI - Relic excavated in western India is probably of Georgian Queen Ketevan.
AB - History has well documented the execution of Queen Ketevan of Georgia by the
Persian Emperor of modern day Iran. Based on historical records, in 1624 two
Augustinian friars unearthed the queen's remains and one of them brought the
relic to the St. Augustine convent in Goa, India. We carried out ancient DNA
analysis on the human bone remains excavated from the St. Augustine convent by
sequencing and genotyping of the mitochondrial DNA. The investigations of the
remains revealed a unique mtDNA haplogroup U1b, which is absent in India, but
present in Georgia and surrounding regions. Since our genetic analysis
corroborates archaeological and literary evidence, it is likely that the
excavated bone belongs to Queen Ketevan of Georgia.
PMID- 24355297
TI - Mechanisms which help explain implementation of evidence-based practice in
residential aged care facilities: a grounded theory study.
AB - BACKGROUND: The context for the study was a nation-wide programme in Australia to
implement evidence-based practice in residential aged care, in nine areas of
practice, using a wide range of implementation strategies and involving 108
facilities. The study drew on the experiences of those involved in the programme
to answer the question: what mechanisms influence the implementation of evidence
based practice in residential aged care and how do those mechanisms interact?
METHODS: The methodology used grounded theory from a critical realist
perspective, informed by a conceptual framework that differentiates between the
context, process and content of change. People were purposively sampled and
invited to participate in semi-structured interviews, resulting in 44 interviews
involving 51 people during 2009 and 2010. Participants had direct experience of
implementation in 87 facilities, across nine areas of practice, in diverse
locations. Sampling continued until data saturation was reached. The quality of
the research was assessed using four criteria for judging trustworthiness:
credibility, transferability, dependability and confirmability. RESULTS: Data
analysis resulted in the identification of four mechanisms that accounted for
what took place and participants' experiences. The core category that provided
the greatest understanding of the data was the mechanism On Common Ground,
comprising several constructs that formed a 'common ground' for change to occur.
The mechanism Learning by Connecting recognised the ability to connect new
knowledge with existing practice and knowledge, and make connections between
actions and outcomes. Reconciling Competing Priorities was an ongoing mechanism
whereby new practices had to compete with an existing set of constantly shifting
priorities. Strategies for reconciling priorities ranged from structured
approaches such as care planning to more informal arrangements such as
conversations during daily work. The mechanism Exercising Agency bridged the gap
between agency and action. It was the human dimension of change, both
individually and collectively, that made things happen. CONCLUSIONS: The findings
are consistent with the findings of others, but fit together in a novel way and
add to current knowledge about how to improve practices in residential aged care.
Each of the four mechanisms is necessary but none are sufficient for
implementation to occur.
PMID- 24355296
TI - A histone deacetylase inhibitor YCW1 with antitumor and antimetastasis properties
enhances cisplatin activity against non-small cell lung cancer in preclinical
studies.
AB - Many histone deacetylase (HDAC) inhibitors show limited therapeutic effects for
solid tumors. Here, we develop a novel HDAC inhibitor YCW1 and verify the
combination effect of YCW1 and cisplatin in lung cancer pre-clinical models. YCW1
exerted cancer-specific cytotoxicity via mitochondria-mediated apoptosis. YCW1
and cisplatin showed synergistic anti-tumor effects through impairment of DNA
damage repair. YCW1 inhibited tumor growth in lung orthotopic and subcutaneously
implanted xenograft models. YCW1 significantly suppressed lung metastases via
inhibition of focal adhesion complex. Our findings suggested that YCW1 is a
potential HDAC inhibitor for lung cancer treatment as single and in combination
regimens with cisplatin.
PMID- 24355298
TI - GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2.
AB - Osteoblasts are specialized mesenchymal cells that are responsible for bone
formation. In this study, we examine the role of GATA4 in osteoblast
differentiation. GATA4 was abundantly expressed in preosteoblast cells and
gradually down-regulated during osteoblast differentiation. Overexpression of
GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule
formation in osteogenic conditioned cell culture system. In addition,
overexpression of GATA4 attenuated expression of osteogenic marker genes,
including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of
which are important for osteoblast differentiation and function. Overexpression
of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased
Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently
decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that
GATA4 acts as a negative regulator in osteoblast differentiation by
downregulation of Runx2.
PMID- 24355299
TI - Evidence of complex formation between FADD and c-FLIP death effector domains for
the death inducing signaling complex.
AB - Adaptor protein FADD forms the death inducing signaling complex (DISC) by
recruiting the initiating caspases-8 and -10 through homotypic death effector
domain (DED) interactions. Cellular FLICE-inhibitory protein (c-FLIP) is an
inhibitor of death ligand-induced apoptosis downstream of death receptors, and
FADD competes with procaspase-8/10 for recruitment for DISC. However, the
mechanism of action of FADD and c-FLIP proteins remain poorly understood at the
molecular level. In this study, we provide evidence indicating that the death
effector domain (DED) of FADD interacts directly with the death effector domain
of human c-FLIP. In addition, we use homology modeling to develop a molecular
docking model of FADD and c-FLIP proteins. We also find that four structure-based
mutants (E80A, L84A, K169A and Y171A) of c-FLIP DEDs disturb the interaction with
FADD DED, and that these mutations lower the stability of the c-FLIP DED.
PMID- 24355301
TI - Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy
(BNCT).
AB - The first BNCT trials took place in the USA in the early 1960's, yet BNCT is
still far from mainstream medicine. Nonetheless, in recent years, reported
results in the treatment of head and neck cancer and recurrent glioma, coupled
with the progress in developing linear accelerators specifically for BNCT
applications, have given some optimism to the future of BNCT. This article
provides a brief reminder on the ups and downs of the history of BNCT and
supports the view that controlled and prospective clinical trials with a modern
design will make BNCT an evidence-based treatment modality within the coming
decade.
PMID- 24355300
TI - Microorganism lipid droplets and biofuel development.
AB - Lipid droplet (LD) is a cellular organelle that stores neutral lipids as a source
of energy and carbon. However, recent research has emerged that the organelle is
involved in lipid synthesis, transportation, and metabolism, as well as mediating
cellular protein storage and degradation. With the exception of multi-cellular
organisms, some unicellular microorganisms have been observed to contain LDs. The
organelle has been isolated and characterized from numerous organisms.
Triacylglycerol (TAG) accumulation in LDs can be in excess of 50% of the dry
weight in some microorganisms, and a maximum of 87% in some instances. These
microorganisms include eukaryotes such as yeast and green algae as well as
prokaryotes such as bacteria. Some organisms obtain carbon from CO2 via
photosynthesis, while the majority utilizes carbon from various types of biomass.
Therefore, high TAG content generated by utilizing waste or cheap biomass,
coupled with an efficient conversion rate, present these organisms as bio-tech
'factories' to produce biodiesel. This review summarizes LD research in these
organisms and provides useful information for further LD biological research and
microorganism biodiesel development.
PMID- 24355302
TI - A simple method for determining the activity of large-area beta sources
constructed from anodized aluminum foils.
AB - A simple method has been developed for determining the activity of large-area
beta reference sources in anodized aluminum foils. It is based on the modeling of
the transmission of beta rays through thin foils in planar geometry using Monte
Carlo simulation. The method was checked experimentally and measurement results
show that the activity of large-area beta reference sources in anodized aluminum
foils can be measured with standard uncertainties smaller than the limit of 10%
required by ISO 8769.
PMID- 24355303
TI - Multi-layer 235UF4-6LiF-Au targets for high-resolution fission fragment
measurements.
AB - Multi-layer (235)UF4-(6)LiF-Au targets have been produced by vacuum deposition on
thin polyimide foils with an areal density, measured by spectrophotometry, of
about 33ugcm(-2). The foils were first covered with an Au-layer and then, with a
second layer of (6)LiF, both by vapour deposition. The (235)UF4 layer was
prepared by fluoride sublimation. Each deposited mass was characterized
separately by means of differential weighing for the Au and (6)LiF layers and by
low-geometry alpha-particle counting for the (235)UF4 layer. The atomic
abundances of the uranium base material have been measured by thermal ionization
mass spectrometry. The targets were prepared for measuring fission-fragment
emission yields with high mass-resolution.
PMID- 24355304
TI - High-resolution alpha-particle spectrometry of 238U.
AB - The alpha-particle emission probabilities associated with the three main alpha
transitions of (238)U were measured by high-resolution alpha-particle
spectrometry. Highly enriched (238)U material was used and its isotopic
composition characterised by mass spectrometry. Source production through
electrodeposition was optimised to reconcile conflicting demands for good
spectral resolution and statistical precision. Measurements were performed at
IRMM and CIEMAT for 1-2 years in three different set-ups. A new magnet system was
put into use to largely eliminate true coincidence effects with low-energy
conversion electrons. Finally the accuracy and precision of the relative emission
probabilities for the three transitions - 77.01 (10)%, 22.92 (10)% and 0.068
(10)%, respectively - have been improved significantly.
PMID- 24355305
TI - Calibration of an air monitor prototype for a radiation surveillance network
based on gamma spectrometry.
AB - The objective of this work is to present the improvements that have been made in
quasi-real-time air radioactivity concentration monitors which were initially
based on overall activity determinations, by incorporating gamma spectrometry
into the current prototype. To this end it was necessary to develop a careful
efficiency calibration procedure for both the particulate and the gaseous
fractions of the air being sampled. The work also reports the values of the
minimum detectable activity calculated for different isotopes and acquisition
times.
PMID- 24355306
TI - Critical remarks on gross alpha/beta activity analysis in drinking waters:
conclusions from a European interlaboratory comparison.
AB - The most common gross alpha/beta standard methods used for drinking water
analysis are discussed, and sources of interferences are reviewed from a
metrological point of view. Our study reveals serious drawbacks of gross methods
on the basis of an interlaboratory comparison analyzing commercial mineral water
samples with the participation of 71 laboratories. A proposal is made to obtain
comparable measurement results using true standardized methods.
PMID- 24355307
TI - A portable TDCR system.
AB - The triple-to-double-coincidence ratio method (TDCR) is an important method for
activity standardization in metrology institutes worldwide. There is an
increasing interest in portable systems that allow activity determination outside
of specialized laboratories with high accuracy. Within the framework of the EMRP
"MetroFission" project, several portable systems using different designs were
developed. The PTB system described here is based on channel photomultipliers
incorporated in a portable detection module, a separate electronics bin and a
computer for data acquisition and storage. This miniature TDCR system was
extensively tested and compared to the PTB reference TDCR system that is very
well characterized and has been used in several intercomparisons.
PMID- 24355308
TI - "Realisation of the becquerel"--reducing the impact of equipment failure.
AB - The goal of the CCRI(II) "Realisation of the becquerel" project is to design a
reproducible radioactivity standard which will increase the robustness of the
current international reference system for radioactivity measurements. Tests
performed with a first prototype ionisation chamber of this project, built in
2005, are presented. Based on experience with the first prototype, a new design
was proposed in 2010 aiming at achieving the very ambitious project goals. The
article discusses the status of the project and the advantages of the new design.
PMID- 24355309
TI - Trends in major entry site complications from percutaneous coronary intervention
(from the Dynamic Registry).
AB - Several factors contribute to the risk of percutaneous coronary intervention
related major entry site (MES) complications. We sought to examine the trends in
MES among unselected patients during the stent era. Data from the Dynamic
Registry including 5 distinct recruitment waves from 1997 to 2006 (n = 10,932)
were used to assess baseline characteristics and MES among consecutive patients
undergoing percutaneous coronary intervention. MES was defined as bleeding
requiring transfusion, pseudoaneurysm, arterial thrombosis or dissection,
vascular complication requiring surgery, or retroperitoneal bleed. Uncomplicated
hematomas were not included. Several trends were observed in baseline
characteristics including an increase from wave 1 to wave 5 in body mass index
>30 kg/m(2) (30.2% to 40.4%), renal disease (3.5% to 9.1%), diabetes (28.0% to
34.1%), and hypertension (59.4% to 78%; ptrend <0.001 for all). The use of a
thienopyridine increased significantly from wave 1 (49.7%) to wave 5 (84%),
whereas glycoprotein IIb/IIIa inhibitor use peaked in wave 3 (53.1%) and then
decreased (p <0.001). Access site was predominately femoral, but radial access
increased over time (0.3% wave 1, 6.6% wave 5, p <=0.0001). The rates of MES
(2.8% to 2.2%, ptrend = 0.01) and MES requiring transfusion (2.0% to 0.74%,
ptrend <0.001) were low and decreased with time. The trend in less risk for MES
in later time periods remained after adjustment. In conclusion, MES has decreased
over time; however, opportunity for bleeding avoidance strategies still exists.
PMID- 24355310
TI - Restarting anticoagulation and outcomes after major gastrointestinal bleeding in
atrial fibrillation.
AB - Data regarding the outcomes of restarting anticoagulation in patients who develop
gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized
that restarting anticoagulation in these patients is associated with better
outcomes. This is a retrospective cohort study that enrolled subjects who
developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was
defined by history and electrocardiography on presentation. GIB was defined as a
decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic
evaluation. Time-to-event adjusted analyses were performed to find an association
of restarting warfarin and recurrent GIB, arterial thromboembolism, and
mortality. Stratified analysis by duration of interruption of warfarin was also
performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major
GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was
associated with decreased thromboembolism (hazard ratio [HR] 1.18, 95% confidence
interval [CI] 0.75 to 1.84, p = 0.47) [corrected] and reduced mortality (HR 0.67,
95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to
1.10, p = 0.47). When the outcomes were stratified by duration of warfarin
interruption, restarting warfarin after 7 days was not associated with increased
risk of GIB but was associated with decreased risk of mortality and
thromboembolism compared with resuming after 30 days of interruption. Decision to
restart warfarin after an episode of major GIB is associated with improved
survival and decreased thromboembolism without increased risk of GIB after 7 days
of interruption.
PMID- 24355311
TI - Effect of right ventricular outflow tract obstruction on right ventricular
volumes and exercise capacity in patients with repaired tetralogy of fallot.
AB - Patients with tetralogy of Fallot and combined right ventricular outflow tract
obstruction (RVOTO) and pulmonary regurgitation (PR) have a less dilated right
ventricular (RV) and better RV function compared with patients without RVOTO. It
is not known whether RVOTO is associated with improved exercise capacity. We
compared cardiac magnetic resonance imaging, echocardiography, and exercise tests
in 12 patients with RVOTO (Doppler peak RVOT gradient >=30 mm Hg) and 30 patients
without RVOTO. RV end-systolic and end-diastolic volumes were smaller in patients
with RVOTO compared with patients without RVOTO (50 +/- 16 vs 64 +/- 18 ml/m(2)
and 117 +/- 24 vs 135 +/- 28 ml/m(2), respectively) and patients with RVOTO had a
higher RV mass (52 +/- 14 vs 42 +/- 11 ml/m(2)), p <0.05. RV ejection fraction
was marginally significantly different between both groups (58 +/- 8% vs 53 +/-
7%), p = 0.051. Degree of PR, left ventricular volumes, and function did not
differ significantly between both groups. Peak oxygen uptake in patients with
RVOTO was significantly lower (25 +/- 3 vs 32 +/- 8 ml/kg/min) than in patients
without RVOTO, as was the percentage of predicted peak oxygen uptake (63 +/- 7%
vs 79 +/- 14%), p <0.001. Multivariate analysis showed that the peak RVOT
gradient was the only independent predictor of exercise capacity. In conclusion,
exercise capacity is lower in patients with RVOTO compared with those without
RVOTO despite a less dilated RV and comparable degree of PR. Therefore, exercise
capacity may be of importance and should additionally be taken in consideration
to RV volumes and function in patients with tetralogy of Fallot and PR.
PMID- 24355312
TI - Meta-analysis of global left ventricular function comparing multidetector
computed tomography with cardiac magnetic resonance imaging.
AB - We compare the diagnostic accuracy of multidetector row computed tomography
(MDCT) to cardiac magnetic resonance imaging (CMR) for evaluating global left
ventricular function. We systematically searched PubMed, CINAHL, Cochrane
CENTRAL, Scopus, and the Web of Science databases for studies published between
1966 to January 2013 that compared left ventricle (LV) volumes, ejection fraction
(EF) and LV mass measured by MDCT and CMR. We performed meta-analyses and used
random-effects model with inverse variance weighting test to determine the
overall bias and limits of agreement of LV end-diastolic volume, end-systolic
volume, stroke volume, and EF measured by MDCT and CMR. Furthermore, subgroup
analyses were performed to compare 16-slice and 64-slice MDCT with CMR. Two study
authors independently reviewed the 90 articles originally identified and selected
27 studies (n = 831) for analysis. Excellent correlation and a linear relation
were seen between MDCT and CMR for LV end-diastolic volume (r = 0.93; p <0.001),
LV end-systolic volume (r = 0.95; p <0.001), LV stroke volume (r = 0.85; p
<0.001), LV ejection fraction (r = 0.93; p <0.001), and LV mass (r = 0.86; p
<0.001). Subgroup analyses showed strong positive correlations for both 16- and
64-slice MDCT. In conclusion, although not the first-line test for LV function
assessment in most patients, when appropriate, retrospectively gated MDCT
provides an accurate and valid assessment of LV function compared with CMR.
PMID- 24355313
TI - Antiproliferative activity of methanolic extracts from two green algae,
Enteromorpha intestinalis and Rizoclonium riparium on HeLa cells.
AB - BACKGROUND: Natural compounds can be alternative sources for finding new lead
anti-cancer molecules. Marine algae have been a traditional source for bioactive
compounds. Enteromorpha intestinalis and Rhizoclonium riparium are two well
distributed saline/brackish water algae from Sundarbans. There's no previous
report of these two for their anti-proliferative activities. METHODS:
Cytotoxicity of the algal methanolic extracts (AMEs) on HeLa cells were assayed
by 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (MTT)
reduction assay. Morphological examinations were done by Haematoxylin, Hoechst
33258 and Acridine orange staining. DNA fragmentation was checked. Gene
expressions of Cysteine aspartate protease (Caspase) 3, Tumor protein (TP) 53,
Bcl-2 associated protein X (Bax) were studied by Reverse transcription-
polymerase chain reaction (RT-PCR) keeping Glyceraldehyde 3-phosphate
dehydrogenase (GAPDH) as internal control. Protein expressions were studied for
Caspase 3, phospho-p53, Bax, Microtubule associated proteins-1/ light chain B
(MAP1/LC3B) by western blot. RESULTS: The AMEs were found to be cytotoxic with
Inhibitory concentration 50 (IC50) values 309.048 +/- 3.083 MUg/ml and 506.081 +/
3.714 MUg/ml for E. intestinalis and R. riparium extracts respectively. Treated
cells became round with blebbings with condensed nuclei. Acidic lysosomal
vacuoles formation occurred in treated cells. Expression of apoptotic genes in
both mRNA and protein level was lowered. Expression of LC3B-II suggested
occurrence of autophagy in treated cells. CONCLUSIONS: These two algae can be
potent candidates for isolating new lead anticancer molecules. So they need
further characterization at both molecular and structural levels.
PMID- 24355314
TI - Differential trigeminovascular nociceptive responses in the thalamus in the
familial hemiplegic migraine 1 knock-in mouse: a Fos protein study.
AB - Familial hemiplegic migraine type 1 (FHM-1) is a monogenic subtype of migraine
with aura caused by missense mutations in the CACNA1A gene, which encodes the
pore-forming alpha1 subunit of voltage-gated neuronal CaV2.1 (P/Q-type) calcium
channels. Transgenic knock-in mice expressing the CACNA1A R192Q mutation that
causes FHM-1 in patients show a greater susceptibility to cortical spreading
depression, the likely underlying mechanism of typical human migraine aura. The
aim of this study was to compare neuronal activation within the trigeminal pain
pathways in response to nociceptive trigeminovascular stimulation in wild-type
and R192Q knock-in mice. After sham surgery or electrical stimulation of the
superior sagittal sinus for 2h, or stimulation preceded by treatment with
naratriptan, mice underwent intracardiac perfusion, and the brain, including the
brainstem, was removed. Fos expression was measured in the trigeminocervical
complex (TCC) and the lateral (ventroposteromedial, ventrolateral), medial
(parafascicular, centromedian) and posterior thalamic nuclei. In the TCC of wild
type animals, the number of Fos-positive cells increased significantly following
dural stimulation compared to the sham control group (P<0.001) and decreased
after naratriptan treatment (P<0.05). In R192Q knock-in mice, there was no
significant difference between the stimulated and sham (P=0.10) or naratriptan
pre-treated groups (P=0.15). The number of Fos-positive cells in the R192Q
stimulated group was significantly lower compared to the wild-type stimulated
mice (P<0.05). In the thalamus, R192Q mice tended to be more sensitive to
stimulation compared to the sham control in the medial and posterior nuclei, and
between the two strains of stimulated animals there was a significant difference
in the centromedian (P<0.005), and posterior nuclei (P<0.05). The present study
suggests that the FHM-1 mutation affects more rostral brain structures in this
experimental paradigm, which offers a novel perspective on possible differential
effects of mutations causing migraine in terms of phenotype-genotype
correlations.
PMID- 24355315
TI - Evolution in an acidifying ocean.
AB - Ocean acidification poses a global threat to biodiversity, yet species might have
the capacity to adapt through evolutionary change. Here we summarize tools
available to determine species' capacity for evolutionary adaptation to future
ocean change and review the progress made to date with respect to ocean
acidification. We focus on two key approaches: measuring standing genetic
variation within populations and experimental evolution. We highlight benefits
and challenges of each approach and recommend future research directions for
understanding the modulating role of evolution in a changing ocean.
PMID- 24355316
TI - Two stage treatment of dairy effluent using immobilized Chlorella pyrenoidosa.
AB - BACKGROUND: Dairy effluents contains high organic load and unscrupulous discharge
of these effluents into aquatic bodies is a matter of serious concern besides
deteriorating their water quality. Whilst physico-chemical treatment is the
common mode of treatment, immobilized microalgae can be potentially employed to
treat high organic content which offer numerous benefits along with waste water
treatment. METHODS: A novel low cost two stage treatment was employed for the
complete treatment of dairy effluent. The first stage consists of treating the
diary effluent in a photobioreactor (1 L) using immobilized Chlorella pyrenoidosa
while the second stage involves a two column sand bed filtration technique.
RESULTS: Whilst NH4+-N was completely removed, a 98% removal of PO43--P was
achieved within 96 h of two stage purification processes. The filtrate was tested
for toxicity and no mortality was observed in the zebra fish which was used as a
model at the end of 96 h bioassay. Moreover, a significant decrease in biological
oxygen demand and chemical oxygen demand was achieved by this novel method. Also
the biomass separated was tested as a biofertilizer to the rice seeds and a 30%
increase in terms of length of root and shoot was observed after the addition of
biomass to the rice plants. CONCLUSIONS: We conclude that the two stage treatment
of dairy effluent is highly effective in removal of BOD and COD besides nutrients
like nitrates and phosphates. The treatment also helps in discharging treated
waste water safely into the receiving water bodies since it is non toxic for
aquatic life. Further, the algal biomass separated after first stage of treatment
was highly capable of increasing the growth of rice plants because of nitrogen
fixation ability of the green alga and offers a great potential as a
biofertilizer.
PMID- 24355317
TI - Design and validation of an in vitro loading system for the combined application
of cyclic compression and shear to 3D chondrocytes-seeded agarose constructs.
AB - Physiological loading is essential for the maintenance of articular cartilage by
regulating tissue remodelling, in the form of both catabolic and anabolic
processes. To promote the development of tissue engineered cartilage which
closely matches the long term functionality of native tissue, bioreactors have
been developed to provide a combination of loading modalities, which reflect the
nature of normal physiological loads. This study describes the design and
validation of an in vitro mechanical system for the controlled application of bi
axial loading regimes to chondrocyte-seeded agarose constructs. The computer
controlled system incorporates a robust gripping system, which ensures the
delivery of precise values of cyclic compressive and shear strain to 3D cell
seeded constructs. Sample prototypes were designed, optimised using finite
element analysis and validated performing compressive and shear fatigue
mechanical tests. The horizontal and vertical displacements within the bioreactor
are precisely controlled by a dedicated programme that can be easily implemented.
The synchronisation of the orthogonal displacements was shown to be accurate and
reproducible. Constructs were successfully loaded with a combined compressive and
shear loading regimen at 1 Hz for up to 48 h with no appreciable loss of cell
viability or mechanical integrity. These features along with the demonstrated
high consistency make the system ideally suitable for a systematic investigation
of the response of chondrocytes to a complex physiologically relevant deformation
profile.
PMID- 24355318
TI - The role of drainage after Roux-en-Y gastric bypass for morbid obesity: a
systematic review.
AB - BACKGROUND: Intraperitoneal drainage after gastrointestinal surgery is still
routinely used in many hospitals. The objective of this study was to determine
the evidence-based value of routine drainage after Roux-en-Y gastric bypass
(RYGB). METHODS: An electronic search of the MEDLINE, Cochrane, and Embase
databases from 2002 to 2012 was performed to identify articles analyzing the use
of drainage after RYGB, its efficacy in determining the presence of an
anastomotic leak, and its role in nonoperative treatment of the leakage. RESULTS:
Eighteen articles were identified: 6 nonrandomized prospective cohort studies, 1
cohort retrospective study that compared routine drainage versus no drainage, 11
retrospective cohort studies, and no randomized controlled trials (RCTs). The
sensitivity of drainage in detecting postoperative leakage varied between 0% and
94.1% in 10 articles (3 prospective and 6 retrospective) reporting data about
this matter. The efficacy of drainage for the nonoperative treatment of
postoperative leakage could be estimated in 11 articles (5 prospective and 6
retrospective) and varied between 12.5% and 100%. Only 2 studies reported data
about nonoperative treatment of leakage without drainage, which was pursued in 0%
and 33% of patients, respectively. CONCLUSION: Evidence-based recommendations on
the use of drainage after RYGB cannot be given. Without RCTs, the value of
routine drainage cannot be ascertained.
PMID- 24355319
TI - Gastric cancer: a de novo diagnosis after laparoscopic sleeve gastrectomy.
PMID- 24355320
TI - Predictors of bariatric surgery among an interested population.
AB - BACKGROUND: Severely obese patients considering bariatric surgery face a
difficult decision given the tradeoff between the benefits and risks of surgery.
The objectives of this study was to study the forces driving this decision and
improve our understanding of the decision-making process. METHODS: A 64-item
survey was developed to assess factors in the decision-making process for
bariatric surgery. The survey included the decisional conflict scale, decision
self-efficacy scale, EuroQol 5D, and the standard gamble. Patients were recruited
from a regularly scheduled bariatric surgery interest group meeting associated
with a large, university-based bariatric practice and administered a survey at
the conclusion of the interest group. Logistic regression models were used to
predict who pursued or still planned to pursue surgery at 12 months. RESULTS: 200
patients were recruited over an 8-month period. Mean age was 45 years; mean BMI
was 48 kg/m(2), and 77% were female. The 12-month follow-up rate was 95%. At 12
months, 33 patients (17.6%) had surgery and 30 (16.0%) still planned to have
surgery. There was no association between age, gender, or obesity-associated
conditions and surgery or plan to have surgery. Patients having surgery or still
planning to have surgery had significantly worse scores for quality of life and
better scores for decisional conflict (indicating readiness to make a decision).
CONCLUSION: The decision to have bariatric surgery is strongly associated with
patients' perceptions of their current quality of life. In addition, lower
decisional conflict and higher self-efficacy are predictive of surgery.
Interestingly, factors that clinicians might consider important, such as gender,
age, and the presence of obesity-associated co-morbidities did not influence
patients' decisions.
PMID- 24355322
TI - Laparoscopic sleeve gastrectomy in patients with NASH-related cirrhosis: a case
matched study.
AB - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a validated procedure for the
surgical treatment of morbid obesity. Cirrhosis is often considered a relative
contraindication to elective extrahepatic surgery. The objective of this study
was to evaluate the morbidity related to SG performed in cirrhotic patients
compared with noncirrhotic patients. METHODS: Between March 2004 and January
2013, we included all patients with cirrhosis undergoing SG (13 patients). These
patients (SG-cirrhosis group) were matched in terms of preoperative data (age,
gender, body mass index, and co-morbidities) on a 1:2 basis, with 26 noncirrhotic
patients (SG group) selected from a population of 750 patients. Cirrhosis was
diagnosed postoperatively on histologic exam. The primary endpoint was the
overall postoperative complication rate. Secondary endpoints were operating time,
revisional surgery rate, gastric fistula and bleeding rates, postoperative
mortality, and weight loss over a 24-month period. RESULTS: The SG-cirrhosis
group consisted of 13 patients with a median age of 52 years. All patients in the
SG-cirrhosis group were Child A. Etiology of cirrhosis was related to NASH in
93.3%. Median operating time in the SG-cirrhosis group and SG group was 75
minutes versus 80 minutes (P = .59). No postoperative mortality was observed in
either group. The overall postoperative complication rate was 7.7% versus 7.7% (P
= 1). The major complication rate was 0% versus 7.7% (P = .22), and the
postoperative gastric fistula rate was 0% versus 3.8% (P = .47). No complications
related to cirrhosis were reported. CONCLUSION: SG can be performed in Child A
cirrhosis with no increased risk of postoperative complications and no specific
complications related to cirrhosis. Weight loss for patients with cirrhosis
undergoing SG is similar to that observed in noncirrhotic patients.
PMID- 24355321
TI - The Mini-Mental State Exam (MMSE) is not sensitive to cognitive impairment in
bariatric surgery candidates.
AB - BACKGROUND: Cognitive dysfunction is common among bariatric surgery candidates
and associated with poorer weight loss outcomes. Identification of a brief
screening measure to detect cognitive impairment in this population is needed,
because comprehensive neuropsychological evaluations may not be available in all
clinical settings. METHODS: The present study examined the utility of the Mini
Mental State Examination (MMSE) for detecting cognitive impairment in 30
bariatric surgery candidates by comparing impairment on the MMSE (at varying
cutoffs) to impairment on a comprehensive neuropsychological test battery.
RESULTS: Results indicated that the MMSE showed low sensitivity and specificity
in identifying impairment, even at the more stringent MMSE cutoffs of 27 and 28.
CONCLUSION: These findings suggest that the MMSE is a poor screener for cognitive
impairment in bariatric surgery candidates. Future research is needed to identify
or develop cognitive screeners for use in this population.
PMID- 24355323
TI - Total weight loss associated with increased physical activity after bariatric
surgery may increase the need for total joint arthroplasty.
AB - BACKGROUND: Retrospectively, our institution noticed an increased number of
patients undergoing total joint arthroplasty (TJA) after bariatric surgery.
Considering that bariatric surgery is a proven modality to reduce osteoarthritic
pain, we sought to identify a reason some patients may later require TJA. The
objective of this study was to investigate the hypothesis that rapid or increased
weight loss after bariatric surgery may be a risk factor for TJA. METHODS: Weight
loss parameters were retrospectively assessed in 15 bariatric surgery patients
who subsequently received a primary TJA and compared with matched bariatric
controls. RESULTS: Patients who required a TJA lost 27.9% more of their body mass
index (BMI) compared with controls (P = .049). Furthermore, patients who
underwent TJA 25-48 months postbariatric surgery lost 78.2% more of their BMI
compared with controls (P<.001). Total knee arthroplasty patients lost 43.9% more
of their BMI compared with controls (P = .02), and the difference in BMI change
for total hip arthroplasty patients was not significant versus controls.
CONCLUSION: These results contradict the tenant that weight loss is universally
protective against arthritis and merit larger prospective investigations.
PMID- 24355324
TI - The effect of laparoscopic sleeve gastrectomy with or without hiatal hernia
repair on gastroesophageal reflux disease in obese patients.
AB - BACKGROUND: Obesity is an independent risk factor for gastroesophageal reflux
disease (GERD), which is often associated with the presence of a hiatal hernia
(HH). Despite increasing popularity of laparoscopic sleeve gastrectomy (LSG) in
bariatric surgery, its effect on GERD is still unclear. The objective of this
study was to evaluate the effect of LSG with or without hiatal hernia repair
(HHR) on GERD in obese patients. METHODS: Seventy-eight patients with HH
underwent LSG with concomitant HHR (LSG+HHR group). Their data were compared with
that of 102 patients without HH, who underwent only LSG (LSG-group). All patients
underwent a standardized questionnaire, a double-contrast barium swallow, and an
upper-gastrointestinal endoscopy before the surgical procedure and at least 6
months later. RESULTS: At baseline, the prevalence of GERD symptoms and their
frequency-intensity scores did not differ between groups. At follow up, there was
a significant decrease in the prevalence of typical GERD symptoms only in the LSG
group (P = .003). LSG+HHR patients showed a significantly higher heartburn
frequency-intensity score compared with LSG patients (P = .009). CONCLUSION: This
finding confirms that LSG has a beneficial effect on relieving GERD symptoms,
although the underlying mechanisms are still unclear; conversely, the procedure
of HHR did not produce any improvement in GERD symptoms.
PMID- 24355325
TI - Comment on: the early use of Roux limb as surgical treatment for proximal
postsleeve gastrectomy leaks.
PMID- 24355326
TI - Effects of laparoscopic sleeve gastrectomy on attentional processing of food
related information: evidence from eye-tracking.
AB - BACKGROUND: Weight loss after laparoscopic sleeve gastrectomy (LSG) might be
associated partially with changes in reward system functioning and altered
appetitive responses to food cues. Food cue processing refers to motivational,
affective, and cognitive responses to stimuli that are associated with food. We
investigated if food cue processing is altered 6 months after weight loss that is
induced by LSG. We expected patients after LSG to show reduced appetitive
responses to food cues. METHODS: In an experimental longitudinal exploratory
study, 17 severely obese patients (body mass index [BMI]: 48.3 +/- 6.5 kg/m2)
were investigated presurgery and 6 months postsurgery. We used eye-tracking to
assess attentional biases during free viewing of food versus nonfood cues,
assessed pleasantness ratings of food cues, and self-reported food craving.
RESULTS: After LSG, the mean BMI of patients was 36.4 +/- 6.0 kg/m2, and the
percentage of excess weight loss (%EWL) was 46.6% +/- 14.0%. Six months after
LSG, patients showed an attentional bias toward nonfood cues compared with
presurgery, reported lower food craving, and rated presented food stimuli as less
pleasant. CONCLUSION: Evidence of altered food cue processing was found in
patients after LSG, which may be interpreted as reduced food reward associated
with increased cognitive control. Surgery-induced physiologic, cognitive
motivational, and behavioral changes may lead to a desensitization of the reward
system and enhanced cognitive control.
PMID- 24355327
TI - Frequency of laboratory testing among gastric bypass patients.
AB - BACKGROUND: Long-term laboratory monitoring is recommended after gastric bypass
surgery to prevent the development of micronutrient deficiencies. The objective
of this study was to characterize patterns of laboratory monitoring after
surgery. METHODS: We used a large insurance claims database to assess the
frequency of laboratory testing after gastric bypass surgery. We assessed the
tests recommended by an expert panel on bariatric surgery, including tests
recommended routinely as well as second-line tests for specific clinical
scenarios (e.g., tests for anemia when iron deficiency is not present). RESULTS:
With the exception of testing for diabetes, most gastric bypass patients did not
undergo routine laboratory testing in the first year after their surgery, ranging
from 54% (electrolytes) to 95% (zinc). However, for first-line tests,
significantly more gastric bypass patients underwent testing in the first
year,compared with gastric banding patients. Differences in testing frequency
between gastric bypass and gastric banding patients were larger for tests of
micronutrient deficiency than for common metabolic panels and complete blood
counts. For second-line tests, much smaller percentages of both groups of
patients underwent testing, either in the first year or after year 1. CONCLUSION:
Patients undergoing gastric bypass do not routinely undergo recommended
laboratory tests, although they are undergoing more monitoring than gastric
banding patients. Efforts must be made by patients, surgeons, and primary care
providers to ensure that routine testing is done to lower the risk of adverse
health outcomes.
PMID- 24355328
TI - Anti-apoptotic and pro-survival effect of protocatechuic acid on hypertensive
hearts.
AB - Cardiac apoptosis was found in hearts from hypertensive animals, therefore in
this study we aimed to evaluate the anti-apoptotic and pro-survival effects of
protocatechuic acid (PCA) on hypertensive hearts. At first we found that,
sedentary group (SHR)-PCA group's decreased TUNEL-positive apoptotic cells than
SHR group alone. Protein levels of Fas ligand, Fas death receptor, Fas-associated
death domain (FADD), Bid, t-Bid, Bax, cytochrome c, activated caspase-8,
activated caspase 9 and activated caspase-3 were decreased in SHR-PCA group
compared with SHR group. Moreover, SHR-PCA groups increased pro-survival pathway
proteins like IGF1, pIGF1R, pPI3K, p-Akt, Bcl-xL, and Bcl-2 than SHR and
sedentary normotensive group (WKY). All these finding suggest us that,
Protocatechuic acid prevented hypertension-enhanced cardiac Fas-dependent and
mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival
pathway in rat models.
PMID- 24355329
TI - Where are signal molecules likely to be located in anaerobic granular sludge?
AB - Quorum sensing is a concentration-sensing mechanism that plays a vital role in
sludge granulation. In this study, the regularities of distribution of different
signal molecules, including intra- and interspecific signal molecules (diffusible
signal factor, DSF), interspecific signal molecules (autoinducter-2, AI-2) and
intraspecific signal molecules (acyl-homoserine lactones, AHLs), from three types
of anaerobic granular sludge were investigated. The results showed that 70-90% of
DSF was distributed in sludge, while AI-2 in the Water phase accounted for over
80% of the total content. Interestingly, there was a positive correlation between
DSF and AI-2, which played opposite roles in granulation. Moreover, more than 55%
of short and medium acyl chain AHLs tended to spread in aqueous water, while the
long acyl chain AHLs were closer to granular sludge than the short and medium
acyl chain AHLs. With the exception of one type of sludge, the percentage of long
acyl chain AHLs in the sludge phase was greater than 70%. The different
distributions of signal molecules were primarily determined based on their
physicochemical properties, including molecular weight and solubility in water or
organic solutions. In addition, the basic properties of sludge, such as the
granular level or the production of EPS, were closely related to the diversity,
distribution and concentration of signal molecules. As a medium in granulation,
extracellular polymeric substances production was regulated by different signal
molecules from different parts of anaerobic granular sludge. This study provides
a foundation for investigation of quorum sensing in the system of anaerobic
granular sludge.
PMID- 24355330
TI - The role of temperature and CaCl2 in activated sludge dewatering under
hydrothermal treatment.
AB - Dewatering is important for activated sludge disposal. The dewaterability of
activated sludge was first deteriorated and then ameliorated when the temperature
was raised from 100 to 200 degrees C with a threshold temperature of 130
degrees C under hydrothermal treatment. Calcium chloride assisted hydrothermal
treatment to improve the dewaterability of activated sludge, and eliminated the
threshold temperature at as less as 20 mg/g dry solid (DS). An increase in
temperature and dosage of CaCl2 till 60 mg/g DS allowed a continuous improvement
of dewaterability. It is found that the charge neutralization resulted from
biopolymers solubilization dominated the dewaterability evolution below 160
degrees C, while the decomposition of water-binding components played a more
important role at higher temperatures. The variation of molecular weight of
soluble protein and polysaccharides implies that CaCl2 interacted with the
component of sludge and altered the constituent during the hydrothermal
treatment. The integration of soluble biopolymers into the floc matrix by CaCl2
contributed to the compacted floc structure and thus improved the dewaterability.
This work presents an insight into the floc variation in both the composition and
structure associated with the dewaterability and offers a new understanding to
the role of temperature and CaCl2 in hydrothermal treatment on activated sludge
dewatering.
PMID- 24355331
TI - Birth weight, physical morbidity, and mortality: a population-based sibling
comparison study.
AB - Associations between low birth weight (<=2,500 g) and increased risk of mortality
and morbidity provided the foundation for the "developmental origins of health
and disease" hypothesis. Previous between-family studies could not control for
unmeasured confounders. Therefore, we compared differentially exposed siblings to
estimate the extent to which the associations were due to uncontrolled factors.
Our population cohort included 3,291,773 persons born in Sweden from 1973 to
2008. Analyses controlled for gestational age, among other covariates, and
considered birth weight as both an ordinal and a continuous variable. Outcomes
included mortality after 1 year, cardiac-related death, hypertension, ischemic
heart disease, pulmonary circulation problems, stroke, and type 2 diabetes
mellitus. We fitted fixed-effects models to compare siblings and conducted
sensitivity analyses to test alternative explanations. Across the population, the
lower the birth weight, the greater the risk of mortality (e.g., cardiac-related
death (low birth weight hazard ratio = 2.69, 95% confidence interval: 2.05,
3.53)) and morbidity (e.g., type 2 diabetes mellitus (low birth weight hazard
ratio = 1.79, 95% confidence interval: 1.50, 2.14)) outcomes in comparison with
normal birth weight. All associations were independent of shared familial
confounders and measured covariates. Results emphasize the importance of birth
weight as a risk factor for subsequent mortality and morbidity.
PMID- 24355333
TI - Invited commentary: is it time to retire the "pack-years" variable? Maybe not!
AB - Cumulative exposure--the product of intensity and duration for a constant
exposure rate or its integral over time if variable--has been widely used in
epidemiologic analyses of extended exposures, for example, the "pack-years"
variable for tobacco smoking. Although the effects of intensity and duration are
known to differ for exposures like smoking and ionizing radiation and simple
cumulative exposure does not explicitly allow for modification by other time
related variables, such as age at exposure or time since exposure, the cumulative
exposure variable has the merit of simplicity and has been shown to be one of the
best predictors for many exposure-response relationships. This commentary
discusses recent refinements of the pack-years variable, as discussed in this
issue of the Journal by Vlaanderen et al. (Am J Epidemiol. 2014;179(3):290-298),
in the broader context of general exposure-time-response relationships.
PMID- 24355332
TI - Effect modification of the association of cumulative exposure and cancer risk by
intensity of exposure and time since exposure cessation: a flexible method
applied to cigarette smoking and lung cancer in the SYNERGY Study.
AB - The indiscriminate use of the cumulative exposure metric (the product of
intensity and duration of exposure) might bias reported associations between
exposure to hazardous agents and cancer risk. To assess the independent effects
of duration and intensity of exposure on cancer risk, we explored effect
modification of the association of cumulative exposure and cancer risk by
intensity of exposure. We applied a flexible excess odds ratio model that is
linear in cumulative exposure but potentially nonlinear in intensity of exposure
to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our
model accommodated modification of the excess odds ratio per pack-year of
cigarette smoking by time since smoking cessation among former smokers. We
observed negative effect modification of the association of pack-years of
cigarette smoking and lung cancer by intensity of cigarette smoke for persons who
smoked more than 20-30 cigarettes per day. Patterns of effect modification were
similar across individual studies and across major lung cancer subtypes. We
observed strong negative effect modification by time since smoking cessation.
Application of our method in this example of cigarette smoking and lung cancer
demonstrated that reducing a complex exposure history to a metric such as
cumulative exposure is too restrictive.
PMID- 24355334
TI - Computerized medical imaging and graphics. Editorial note.
PMID- 24355335
TI - Are there more positive alternative celebration opportunities to Schoolies Week?
PMID- 24355336
TI - Building health promotion capacity in a primary health care workforce in the
Northern Territory: some lessons from practice.
AB - ISSUES ADDRESSED: Reorientation of the workforce in primary health care is a
complex process and requires specific strategies and interventions. Primary
health care providers are a key health care workforce that is expected to deliver
tangible outcomes from disease prevention and health promotion strategies. This
paper describes a training intervention that occurred as part of a broader
participatory action research process for building health promotion capacity in
the primary health care workforce. METHODS: Participatory action research (PAR)
was conducted over six action and reflection cycles in a two-year period (2001
02) in an urban community health setting in the Northern Territory. One of the
PAR cycles was a training intervention that was identified as a need from a
survey in the first action and reflection cycle. This training was facilitated by
a health promotion specialist, face-to-face and comprised five 3.5-h sessions
over a 5-month period. A pre-post questionnaire was used to measure the knowledge
and skills components of the training intervention. RESULTS: The results
reinforced the importance of using a participatory approach that involved the
primary health care providers themselves. Multiple strategies such as workforce
development within capacity building frameworks assisted in shifting work
practice more upstream. Additionally, these strategies encouraged more reflective
practice and built social capital within the primary health care workforce.
CONCLUSION: Lessons from practice reinforce that workforce development influenced
work practice change and is an important element in building the health promotion
capacity of primary health care centres. SO WHAT?: Workforce development is
critical for reorienting health services. Health promotion specialists play an
important role in reorienting practice, which is only effective when combined
with other strategies, and driven and led by the primary health care workforce.
PMID- 24355337
TI - Academic and personal problems among Australian university students who drink at
hazardous levels: web-based survey.
AB - ISSUE ADDRESSED: Australian university students consume large amounts of alcohol.
There is little published information about personal and academic problems
associated with this behaviour. We sought to estimate the prevalence, and
identify variables associated with, alcohol-related problems among undergraduate
hazardous drinkers. METHODS: The control group members (942 undergraduates, 53.3%
male, mean age 19.4 years) of an internet-based intervention trial, who scored
>=8 on the Alcohol Use Disorders Identification Test, completed two validated
questionnaires about their experience of alcohol-related problems in the
preceding 4 weeks. Regression models were used to identify associations between
individual characteristics and alcohol-related problems. RESULTS: One-quarter of
participants had missed a class (25.6%) and/or had been unable to concentrate in
class (25.7%), and 45% reported that their drinking had impacted negatively on
their learning or grades. The most frequent non-academic problems were hangovers
(74.8%), blackouts (44.8%), emotional outbursts (30.5%), vomiting (28.1%),
arguments (20.2%) and drink-driving (23.2%). Male gender, lower age, being a
smoker, being in the Faculty of Health (versus Humanities) and living in shared
housing (versus with parents/guardians) were each associated with alcohol-related
problems, whereas year of study had no association. CONCLUSIONS: There is a high
prevalence of preventable alcohol-related problems among undergraduates drinking
at hazardous levels and a need for restriction of the availability and promotion
of alcohol as well as intervention for individuals at high risk. SO WHAT?:
Universities have a duty of care to large populations of young people drinking at
hazardous levels and should make greater efforts to address hazardous alcohol
consumption.
PMID- 24355338
TI - The vocational education setting for health promotion: a survey of students'
health risk behaviours and preferences for help.
AB - BACKGROUND: Adolescence and young adulthood is a time of risky health behaviour
initiation and experimentation. Smoking, risky drinking, poor nutrition and
physical activity, and a lack of sun protection behaviour, often become
established in early adulthood. Levels of health risk behaviours occurring
amongst tertiary education and training students and their preferences for types
of on-campus health promotion programs were examined. METHOD: A cross-sectional
pen-and-paper classroom survey was conducted at one Sydney-based TAFE New South
Wales Institute campus in May 2010. The survey assessed demographics, smoking,
alcohol use, sun protection, nutrition, physical activity and health promotion
program preferences. RESULTS: Two hundred and twenty-four students participated
(97% consent); the majority were aged 16-24 years (59%) and female (51%). Current
smoking (35%), risky drinking (49%) and inadequate physical activity (88%) rates
were high. Adequate vegetable intake (3.6%) and sun protection behaviours (5.4%)
were low and 33% of students were overweight or obese. Popular health promotion
programs included food and activity subsidies, practical skills classes and
social outings. CONCLUSION: Participation in health risk behaviours among this
sample was high. The setting of tertiary education and workplace training
represents an opportunity for early intervention into risky health behaviours
among young people. SO WHAT?: This study is the first to provide information on
the prevalence of health risk behaviours and preferences for types of health
promoting programs among students of an Australian community college. The results
show that young adults regularly participate in multiple health risk behaviours,
such as smoking, drinking, poor nutrition, physical activity and lack of sun
protection.
PMID- 24355339
TI - Can small stores have a big impact? A qualitative evaluation of a store fruit and
vegetable initiative.
AB - ISSUE ADDRESSED: The aim of this evaluation was to explore the quality, barriers,
enablers and outcomes of a retail fresh fruit and vegetable initiative in rural
communities identified to have poor geographic access to healthy food. METHODS: A
qualitative evaluation using in-depth interviews was conducted with rural store
retailers across Victoria involved in the implementation of a retail fruit and
vegetable initiative. Data were analysed using a thematic approach. RESULTS: Six
of the 13 store retailers that were engaged in the initiative identified a range
of qualities, barriers, enablers and outcomes. They reported that effective
communication is essential for engaging retailers and sustaining participation.
The choice and use of retail incentives may influence the community's purchase of
fruit and vegetables. The community's attitude to fruit and vegetables, the
staff's ability to promote produce and the capacity of the store to stock and
sell fresh fruit and vegetables influenced perceived success. Barriers included
difficulties receiving a regular supply of fresh fruit and vegetables, time
constraints and storage facilities. CONCLUSIONS: This qualitative evaluation of a
retail fruit and vegetable initiative found that effective leadership and
communication from project workers, a range of retail incentives and the capacity
of the store to promote, stock and sell fresh fruit and vegetables influenced
perceived success. SO WHAT?: Fruit and vegetable retail initiatives in small
rural community stores may have a role in supporting consumption of fruit and
vegetables.
PMID- 24355340
TI - Young adult perceptions of Australia's physical activity recommendations for
adults.
AB - ISSUES ADDRESSED: Physical activity recommendations for adults worldwide advise
participation in moderate-intensity physical activity, such as walking, on most
days of the week. Younger adults report the lowest prevalence of walking. This
mixed-methods study explores the salience of Australia's activity recommendations
around moderate-intensity physical activity, particularly walking, for young
Australian adults. METHODS: Semistructured interviews were conducted with 24
young Australians aged 17-25 years. During interviews, Australia's physical
activity recommendations for adults were explained to participants, highlighting
the inclusion of moderate-intensity physical activity such as walking.
Participants were asked to comment on the recommendations and walking for
physical activity and exercise. Data from interviews underwent an iterative
thematic form of analysis. Participants also completed the International Physical
Activity Questionnaire (IPAQ) and were asked to complete a pedometer diary.
RESULTS: No participant was classified as sedentary; twenty three participants
reported walking for transport and nine for leisure (IPAQ). During interviews,
the majority of participants (n=20) did not identify walking as physical activity
or exercise. Participants focussed on the cardiorespiratory (fitness) benefits
associated with physical activity and believed walking was of insufficient
intensity to achieve these benefits at their age. CONCLUSIONS: Walking was
considered an everyday activity and of insufficient intensity to achieve any
health or fitness benefits. SO WHAT?: The belief that only vigorous physical
activity conveys any fitness benefits may act as a barrier to participation in
moderate-intensity physical activity such as walking, particularly among
sedentary young people.
PMID- 24355341
TI - Edible gardens in early childhood education settings in Aotearoa, New Zealand.
AB - ISSUE ADDRESSED: This paper aims to explore the presence and role of edible
gardens in Aotearoa/New Zealand Early Childhood Education Services (ECES).
METHODS: Participant ECES providers were identified from the Ministry of
Education database of Early Childhood Education Services (March 2009). These
include Education and Care and Casual Education and Care, Kindergarten, Home
based Education and Care services, Playcentres, Te Kohanga Reo. A structured,
self-administered questionnaire was sent to the Principal or Head Teacher of the
service. RESULTS: Of the 211 ECES that responded (55% response rate), 71% had
edible gardens, incorporating vegetables, berry fruit, tree fruit, edible flowers
and nut trees. Garden activities were linked with teaching across all strands of
the New Zealand early childhood curriculum. In addition, 34% provided guidance on
using garden produce and 30% linked the garden with messages on fruit and
vegetable consumption. Most gardens were established recently (past 2 years) and
relied on financial and non-financial support from parents, teachers and
community organisations. Barriers included a lack of funding, space, time and
staff support. CONCLUSIONS/IMPLICATIONS: Study findings suggest that gardens are
already being used as a versatile teaching tool in many ECES settings. Most
gardens are new, with a need to support the sustainability and workforce
development among teachers and parents in order to be able to maintain these
resources for future generations. SO WHAT?: Given the inherent links between
gardening and healthy food and exercise, there seem to be extensive opportunities
for health promotion aligned with the edible garden movement.
PMID- 24355342
TI - Sitting time, physical activity and cervical intraepithelial neoplasia in
Australian women: a preliminary investigation.
AB - ISSUE ADDRESSED: Physical activity affects the immune system, which in turn may
modify the risk of cervical intraepithelial neoplasia (CIN). The effect of
sitting on CIN is unknown. This study investigated the relationship between
sitting time, physical activity and the risk of CIN. METHODS: Community-dwelling
adult women within metropolitan Perth, Western Australia, who had had a
Papanicolaou (Pap) smear test at any of five clinics and medical centres, were
approached by their general practitioners. In total, 348 women were recruited and
interviewed for information on sitting time, physical activity level and lifetime
physical activity exposure using the International Physical Activity
Questionnaire (IPAQ)--short form. Associations of exposure variables with CIN
risk were assessed by unconditional logistic regression analyses. RESULTS: The
prevalence of abnormal Pap smear status indicating CIN was found to be 15.8%.
Women with prolonged sitting duration (>=42 h per week) had significantly
increased risk of CIN (adjusted OR 3.49, 95% CI 1.12-10.88) than women who sat
less than 24.5h per week. Although the effect of total physical activity level
was non-significant (P=0.408), being always involved in physical activity during
the entire life appeared to be inversely associated with the CIN risk (P=0.036).
CONCLUSIONS: Prolonged sitting time was significantly associated with increased
risk of abnormal Pap smear status indicating CIN. SO WHAT?: This preliminary
investigation highlights a new prospect for health-promotion intervention to
reduce the risk of CIN. Health practitioners should encourage women to reduce
their sitting time and maintain physically active throughout their life course.
PMID- 24355344
TI - Key influences on motivations for utility cycling (cycling for transport to and
from places).
AB - ISSUE ADDRESSED: Although increases in cycling in Brisbane are encouraging,
bicycle mode share to work (the proportion of people travelling to work by
bicycle) in the state of Queensland remains low. The aim of this qualitative
study was to draw upon the lived experiences of Queensland cyclists to understand
the main motivators for utility cycling (cycling as a means to get to and from
places) and compare motivators between utility cyclists (those who cycle for
utility as well as for recreation) and non-utility cyclists (those who cycle only
for recreation). METHODS: For an online survey, members of a bicycle group (831
utility cyclists and 931 non-utility cyclists, aged 18-90 years) were asked to
describe, unprompted, what would motivate them to engage in utility cycling (more
often). Responses were coded into themes within four levels of an ecological
model. RESULTS: Within an ecological model, built environment influences on
motivation were grouped according to whether they related to appeal (safety),
convenience (accessibility) or attractiveness (more amenities) and included
adequate infrastructure for short trips, bikeway connectivity, end-of-trip
facilities at public locations and easy and safe bicycle access to destinations
outside of cities. A key social-cultural influence related to improved
interactions among different road users. CONCLUSIONS: The built and social
cultural environments need to be more supportive of utility cycling before even
current utility and non-utility cyclists will be motivated to engage (more often)
in utility cycling. SO WHAT?: Additional government strategies and more and
better infrastructure that support utility cycling beyond commuter cycling may
encourage a utility cycling culture.
PMID- 24355343
TI - A randomised controlled trial of an active telephone-based recruitment strategy
to increase childcare-service staff attendance at a physical activity and
nutrition training workshop.
AB - ISSUE ADDRESSED: Centre-based childcare services represent a promising setting to
target the prevention of excessive weight gain in preschool-aged children. Staff
training is a key component of multi-strategy interventions to improve
implementation of effective physical activity and nutrition promoting practices
for obesity prevention in childcare services. This randomised controlled trial
aimed to examine whether an active telephone-based strategy to invite childcare
service staff to attend a training workshop was effective in increasing the
proportion of services with staff attending training, compared with a passive
strategy. METHODS: Services were randomised to an active telephone-based or a
passive-recruitment strategy. Those in the active arm received an email
invitation and one to three follow-up phone calls, whereas services in the
passive arm were informed of the availability of training only via newsletters.
The proportion of services with staff attending the training workshop was
compared between the two arms. RESULTS: One hundred and twenty-eight services
were included in this study. A significantly larger proportion (52%) of services
in the active arm compared with those in the passive-strategy arm (3.1%) attended
training (d.f.=1, chi2=34.3; P<0.001). CONCLUSIONS: An active, telephone-based
recruitment strategy significantly increased the proportion of childcare services
with staff attending training. Further strategies to improve staff attendance at
training need to be identified and implemented. SO WHAT?: Active-recruitment
strategies including follow-up telephone calls should be utilised to invite staff
to participate in training, in order to maximise the use of training as an
implementation strategy for obesity prevention in childcare services.
PMID- 24355346
TI - Unusual new signs of pneumothorax at lung ultrasound.
AB - BACKGROUND: The diagnosis of pneumothorax with a bedside lung ultrasound is a
powerful methodology. The conventional lung ultrasound examination consists of a
step-by-step procedure targeted towards the detection of four classic ultrasound
signs, the lung sliding, the B lines, the lung point and the lung pulse. In most
cases, a combination of these signs allows a safe diagnosis of pneumothorax.
However, the widespread application of sonographic methodology in clinical
practice has brought out unusual cases which raise new sonographic signs. The
purpose of this article was to introduce some of these new signs that are
described after the analysis of unusual and complex cases encountered during the
clinical daily practice in an emergency department. FINDINGS: The double lung
point consists of the alternating patterns of sliding and non-sliding lung
intermittently appearing at the two opposite sides of the scan. The septate
pneumothorax allows B lines and lung pulse to be still visible in a condition of
pneumothorax with absent sliding. In hydropneumothorax, the air/fluid border is
imaged by lung ultrasound as the interposition between an anechoic space and a
non-sliding A-pattern, a sign that may be named hydro-point. CONCLUSIONS: In
bedside lung ultrasound, the operator should be aware and interpret double lung
point, septate pneumothorax and hydro-point. The conventional diagnostic protocol
of bedside lung ultrasound for pneumothorax should be occasionally adapted to
such complex cases.
PMID- 24355347
TI - Matrix metalloproteinase enzymes and their naturally derived inhibitors: novel
targets in photocarcinoma therapy.
AB - The continuous exposure of skin to ultraviolet radiations generates reactive
oxygen species leading to photoaging in which degradation of dermal collagen and
degeneration of elastic fibers occurs. Matrix metalloproteinase [MMP] enzymes are
the proteolytic enzymes which have significant potentiality of cleaving
extracellular matrix [ECM] against Ultraviolet [UV] radiation. The important MMPs
are MMP1, MMP2 and MMP7 which promote skin cancer when irradiated by UV rays. In
lieu of this, the investigation of MMPs and their inhibitors are constantly being
studied for successive results. Recent researches have focused on some
traditionally used bioactive moieties as natural matrix metalloproteinases
inhibitors (MMPIs) and emphasized on the need of more extensive and specific
studies on MMPIs, so that a good combination of natural or synthetic MMPIs with
the conventional drugs can be evolved for cancer chemotherapy. In this review, we
discuss the current view on the feasibility of MMPs as targets for therapeutic
intervention in cancer. This review also summarizes the role of small molecular
weight natural MMPIs and a clinical update of those natural MMPIs that are under
clinical trial stage.
PMID- 24355348
TI - 4-Thiazolidinones: the advances continue....
AB - The diversity in the biological response of 4-thiazolidinones has attracted the
attention of many researchers to explore this framework for its potential. It is,
therefore, of prime importance that the study of this topic and the development
of new synthetic strategies should be based on the most recent knowledge,
emerging from the latest research. This review is an endeavor to highlight the
progress in the chemistry and biological activity of the 4-thiazolidinones,
predominantly after 2006. The last section of the review encompasses the various
patents granted on 4-thiazolidinone analogs/derivatives with World Intellectual
Proprietary Organization (WIPO) and United State Patent Trademark Office (USPTO),
particularly in the duration of the year 2000 to the year 2012.
PMID- 24355349
TI - Stern but illuminating words on imaging: an internist replies.
PMID- 24355350
TI - Reading fiction.
PMID- 24355351
TI - Wandering acute myocardial infarction.
PMID- 24355352
TI - Beware of underlying malignancy: acquired ichthyosis.
PMID- 24355353
TI - D-dimer to rule out pulmonary embolism in renal insufficiency.
AB - BACKGROUND: D-dimer levels are often elevated in renal insufficiency. The
diagnostic accuracy of D-dimer to rule out pulmonary embolism in patients with
renal insufficiency is unclear. METHODS: We evaluated the data of patients
presenting to our Emergency Department and receiving computed tomography
angiography to rule out pulmonary embolism with measurement of D-dimer and
creatinine. Glomerular filtration rate was calculated using the Chronic Kidney
Disease Epidemiology Collaboration formula. RESULTS: There were 1305 patients
included; 1067 (82%) had an estimated glomerular filtration rate (eGFR) exceeding
60 mL/min, 209 (16%) 30-60 mL/min, and 29 (2%) <30 mL/min. One hundred fifty-two
patients (12%) had D-dimer below 500 MUg/L. eGFR (R = -0.1122) correlated
significantly with D-dimer (P <.0001). One hundred sixty-nine patients (13%) were
found to have pulmonary embolism. Sensitivity of D-dimer for patients with an
eGFR >60 mL/min was 96% (confidence interval [CI], 0.93-0.99) and 100% (CI, 100
100) for those with 30-60 mL/min, while specificity decreased significantly with
impaired renal function. Area under the curve of the receiver operating
characteristic for D-dimer was 0.734 in patients with an eGFR of >60 mL/min, and
0.673 for 30-60 mL/min. CONCLUSIONS: D-dimer levels were elevated in patients
with an eGFR <60 mL/min, but proved to be highly sensitive for the exclusion of
pulmonary embolism. However, because almost all patients with impaired renal
function had elevated D-dimer irrespective of the presence of pulmonary embolism,
studies should be performed to determine renal function-adjusted D-dimer cutoffs.
PMID- 24355354
TI - Patent foramen ovale and migraine attacks: a systematic review.
AB - BACKGROUND: Migraine headache and the presence of a patent foramen ovale have
been associated with each other, although the precise pathophysiological
mechanism(s) are uncertain. The purpose of this systematic review was to identify
the extent of patent foramen ovale prevalence in migraineurs and to determine
whether closure of a patent foramen ovale would improve migraine headache.
METHODS: An electronic literature search was performed to select studies between
January 1980 and February 2013 that were relevant to the prevalence of patent
foramen ovale and migraine, and the effects of intervention(s) on migraine
attacks. Of the initial 368 articles presented by the initial search, 20
satisfied the inclusion criteria assessing patent foramen ovale prevalence in
migraineurs and 21 presented data on patent foramen ovale closure. RESULTS: In
case series and cohort studies, patent foramen ovale prevalence in migraineurs
ranged from 14.6% to 66.5%. Case-control studies reported a prevalence ranging
from 16.0% to 25.7% in controls, compared with 26.8% to 96.0% for migraine with
aura. The extent of improvement or resolution of migraine headache attack
symptoms was variable. In case series, intervention ameliorated migraine headache
attack in 13.6% to 92.3% of cases. One single randomized trial did not show any
benefit from patent foramen ovale closure. The data overall do not exclude the
possibility of a placebo effect for resolving migraine following patent foramen
ovale closure. CONCLUSION: This systematic review demonstrates firstly that
migraine headache attack is associated with a higher prevalence of patent foramen
ovale than among the general population. Observational data suggest that some
improvement of migraine would be observed if the patent foramen ovale were to be
closed. A proper assessment of any interventions for patent foramen ovale closure
would require further large randomized trials to be conducted given uncertainties
from existing trial data.
PMID- 24355355
TI - The effect of new duty hours on resident academic performance and adult
resuscitation outcomes.
AB - BACKGROUND: From July 2011, the Accreditation Council for Graduate Medical
Education implemented new resident duty hours throughout the US. This study aimed
to determine whether changes to call schedules due to these new duty hours
achieved the intended goals of excellent patient care and improved resident
learning. METHODS: We conducted a retrospective cohort study at an academic
hospital. For patient outcomes, we used the hospital registry for code blues and
rapid responses to compare the proportion of deaths and transfers to an intensive
care unit (July 2010 to June 2011; July 2011 to June 2012). For resident
learning, we compared delta percentage scores for annual in-service training
examinations (2009 to 2010; 2010 to 2011; 2011 to 2012). RESULTS: We recorded 187
code blues and 469 rapid responses during the 2-year period: 48 (7.3%) deaths,
374 (57.0%) transfers to the intensive care unit, and 234 (35.7%) stabilizations
on the floor. Of all transfers to the intensive care unit, those due to a code
blue decreased after implementation of the new duty hours (36% [63/174] vs 25%
[49/200], P = .02; adjusted odds ratio = 0.59; 95% confidence interval, 0.37
0.92). The median (interquartile range) delta percentage scores for annual in
service training examinations decreased significantly from the first time-period
(2009 to 2010: 7 [4-11]) to the third time-period (2011 to 2012: 5 [2-8], P =
.02). CONCLUSION: We observed a reduced proportion of transfers to the intensive
care unit with a code blue after implementation of new resident duty hours.
Resident academic performance experienced a small but significant decrease in in
service training examination delta percentage score. We need large, multicenter
studies to corroborate these findings.
PMID- 24355356
TI - Cannabinoid hyperemesis syndrome: cyclical vomiting behind the cloud of smoke.
PMID- 24355357
TI - Longest survival of lung metastatic ameloblastoma with a rare cause of malignant
hypercalcemia.
PMID- 24355358
TI - Nerve lesions following apical extrusion of non-setting calcium hydroxide: a
systematic case review and report of two cases.
AB - We present two cases of apical extrusion of non-setting, calcium hydroxide paste
which had been placed as an interappointment root canal dressing during routine
endodontic treatment resulting in tissue necrosis of a large part of the
mandible. Surgical intervention consisted of resections in both instances. In
relation to the cases presented, a systematic review of similar cases in the
literature between 1980 and April 2013 was conducted which resulted in eight
cases meeting the criteria outlined. As with the two presented cases, half of
these eight cases showed serious adverse effects and the use of an injectable
system had most often been related to apical extrusion. Consequently, great care
should be taken when applying the paste into the canal system.
PMID- 24355359
TI - Learning deficits and suppression of the cell proliferation in the hippocampal
dentate gyrus of offspring are attenuated by maternal chewing during prenatal
stress.
AB - Prenatal stress in dams induces learning deficits and suppresses neurogenesis in
the hippocampal dentate gyrus (DG) of offspring via increasing corticosterone
levels in the dam. Chewing under stressful conditions prevents stress-induced
behavioral impairments and morphologic changes. Here, we examined whether chewing
during prenatal stress prevents the stress-induced learning deficits and the
suppression of cell proliferation in the hippocampal DG in adult offspring.
Pregnant mice were exposed to restraint stress beginning on day 12 of pregnancy
and continuing until delivery. Half of the dams were given a wooden stick to chew
on during restraint. The pups were raised to adulthood, and learning ability and
cell proliferation in the hippocampal DG were assessed. In dams, chewing during
prenatal stress attenuated the stress-induced increase in plasma corticosterone
levels. In the adult offspring, prenatal stress impaired learning and decreased
cell proliferation in the DG, whereas maternal chewing during prenatal stress
significantly attenuated the prenatal stress-induced learning deficits and
decreased cell proliferation in the DG in their offspring. These findings suggest
that maternal chewing during prenatal stress is an effective stress-coping method
for the dam to prevent learning deficits and suppression of cell proliferation in
offspring.
PMID- 24355360
TI - Cerebrovascular perfusion among older adults is moderated by strength training
and gender.
AB - Cerebral perfusion is important in older adults as it is linked to cognitive
declines. Physical activity can improve blood flow in the body but little is
known about the relationship between physical activity and cerebral perfusion in
older adults. In particular, no study has investigated the relation between
strength training and cerebral perfusion. We examined whether different types of
physical activity (assessed with the Rapid Assessment of Physical Activity
questionnaire) were associated with MRI cerebrovascular perfusion in 59 older
adults. There was a significant interaction between gender and strength training,
such that women who engaged in strength training (weight lifting or calisthenics)
at least once per week exhibited significantly greater cerebrovascular perfusion
than women who did not. This interaction remained significant after controlling
for other physical activity, demographics, and health variables. These findings
suggest that regular strength training can be beneficial for cerebrovascular
health in women.
PMID- 24355361
TI - The kinin B1 receptor mediates alloknesis in a murine model of inflammation.
AB - Noxious stimuli and non-noxious mechanical stimuli elicit itch (alloknesis)
instead of pain on skin lesions of patients with atopic dermatitis. We previously
found that bradykinin evokes an itch-related scratching response through
activation of kinin B1 receptor in skin inflamed using complete Freund's
adjuvant. In this study we investigated whether alloknesis is evoked in CFA
inflamed skin and the involvement of kinin receptors. In our results, alloknesis
was elicited four days after CFA-inflammation. Furthermore, pretreatment with a
B1 receptor antagonist or MU-opioid receptor antagonist significantly reduced
alloknesis. In contrast, treatment with a B2 receptor antagonist significantly
increased alloknesis. These results suggest that the alloknesis response is
mediated by the activation of kinin B1 receptor but antagonized by the B2
receptor in CFA-inflamed mice.
PMID- 24355363
TI - Sensorimotor gating deficits in multiple system atrophy: comparison with
Parkinson's disease and idiopathic REM sleep behavior disorder.
AB - BACKGROUND: Prepulse inhibition (PPI) of the auditory blink reflex is a measure
of sensorimotor gating, which reflects an organism's ability to filter out
irrelevant sensory information. PPI has never been studied in patients with
multiple system atrophy (MSA), although sensorimotor deficits are frequently
associated with synucleinopathies. We investigated whether alterations in PPI
were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic
rapid eye movement sleep behavior disorder (iRBD) and healthy controls. METHODS:
10 patients with MSA, 12 patients with iRBD, 40 patients with PD, and 20 healthy
controls completed the study. A passive acoustic prepulse inhibition paradigm was
applied with prepulses 5 dB and 15 dB above background noise at 30-, 60-, 120-
and 300-ms intervals. RESULTS: Non-parametric analyses showed that MSA patients
had significantly lower prepulse inhibition, as measured with max-amplitude, than
PD patients and iRBD patients on the 60 ms-85 dB and 120 ms-85 dB inter-stimulus
intervals. The same relation was found when using area under the curve. No
differences were found between groups for the 30 ms-85 dB and 300 ms-85 dB.
Furthermore, blink reflex characteristics such as habituation did not differ
between patients and controls. CONCLUSIONS: The present study showed that
sensorimotor gating, as measured with PPI, is markedly reduced in MSA. This may
be due to the pronounced severity of striatal and brainstem dysfunction, as well
as the degeneration of other structures related to the PPI modulating pathways in
MSA. PPI may be a non-invasive neurophysiological measure that can aid in the
differential diagnosis between PD and MSA.
PMID- 24355362
TI - Thymic neoplasms: an update on the use of chemotherapy and new targeted
therapies. A literature review.
AB - Thymic malignancies represent a wide range of clinical, histological and
molecular entities, with probably considerable heterogeneity even among tumors of
the same histotype. Systemic chemotherapy with cisplatin-based regimens continues
to represent the standard of care in metastatic or inoperable
refractory/recurrent diseases and ADOC regimen (including cisplatin, doxorubicin,
vincristine and cyclophosphamide) demonstrated the longer overall response rate
and median survival in the first line setting, although no randomized trial is
available; and there is still a lack of standard treatment after first-line
failure. To date research efforts are focused on translational studies on
molecular pathways involved in thymic tumors carcinogenesis, aimed to better
understand and predict the efficacy of chemotherapy and targeted therapy. Recent
molecular characterization includes identification of a number of oncogenes,
tumor suppressor genes, chromosomal aberrations, angiogenic factors, and tumor
invasion factors involved in cellular survival and proliferation and in tumor
growth. The use of biologic drugs is currently not recommended in a routine
practice because there are limited data on their therapeutic role in thymic
epitelial tumors. Because of the lack of data from adequate-sized, prospective
trials are required for validation and the enrolment of patients with advanced
disease into available clinical trials has to be encouraged.
PMID- 24355364
TI - Targeting opioid receptors with pharmacological chaperones.
AB - G protein-coupled receptors (GPCRs) are polytopic membrane proteins that have a
pivotal role in cellular signaling. Like other membrane proteins, they fold in
the endoplasmic reticulum (ER) before they are transported to the plasma
membrane. The ER quality control monitors the folding process and misfolded
proteins and slowly folding intermediates are targeted to degradation in the
cytosol via the ubiquitin-proteasome pathway. The high efficiency of the quality
control machinery may lead to the disposal of potentially functional receptors.
This is the major underlying course for loss-of-function conformational diseases,
such as retinitis pigmentosa, nephrogenic diabetes insipidus and early onset
obesity, which involve mutant GPCRs. During the past decade, it has become
increasingly evident that small-molecular lipophilic and pharmacologically
selective receptor ligands, called pharmacological chaperones (PCs), can rescue
these mutant receptors from degradation by stabilizing newly synthesized
receptors in the ER and enhancing their transport to the cell surface. This has
raised the interesting prospect that PCs might have therapeutic value for the
treatment of conformational diseases. At the same time, accumulating evidence has
indicated that wild-type receptors might also be targeted by PCs, widening their
therapeutic potential. This review focuses on one GPCR subfamily, opioid
receptors that have been useful models to unravel the mechanism of action of PCs.
In contrast to most other GPCRs, compounds that act as PCs for opioid receptors,
including widely used opioid drugs, target wild-type receptors and their common
natural variants.
PMID- 24355365
TI - Lung cancer neovascularisation: Cellular and molecular interaction between
endothelial and lung cancer cells.
AB - BACKGROUND: Novel vascular-independent conduits have been observed in some
cancers. These have been variously described as vasculogenic mimicry, mosaic
vessel formation, vascular co-option and intratumour embryonic-like
vasculogenesis. Despite lung cancer being the most common cancer worldwide, there
is little information on its neovascularisation or the pathways involved.
METHODS: An in vitro model involving co-cultures of microvascular lung
endothelial cells and squamous or adenocarcinoma lung cancer cells was developed
to assess their angiogenic interaction. Cells were incubated and examined by
phase contrast microscopy and by immunocytochemistry in both mono- and co
cultures. Cultured cells and lung cancer tissue sections were assessed for new
tumour vessel formation, expression of the endothelial marker CD31 and
morphology. RESULTS: Lung tumour cells and endothelial cells interacted
morphologically via pseudopodia and used alternative pathways to generate new
vessels. Co-culturing microvascular endothelial and squamous carcinoma cells led
to endothelial cells surrounding tumour cells and the tumour cells being
incorporated into vessel walls. Co-culturing endothelial and adenocarcinoma cells
resulted in cellular contact and the formation of tumour cell bridges around
clusters of endothelial cells. These adencocarcinoma cells became strongly
positive for CD31. Tumour tissue section studies supported the in vitro findings.
CONCLUSION: Lung carcinoma cells when co-cultured with lung endothelial cells
modify their cellular and molecular features that encourage alternative means of
providing blood supply. The mechanisms underpinning these non-angiogenic
processes need to be further investigated and should be considered when anti
tumour therapeutic interventions are being considered.
PMID- 24355366
TI - Images in emergency medicine. Man with air below the right diaphragm.
Chilaiditi's sign.
PMID- 24355367
TI - Infectious disease/CDC update. Detection of acute HIV infection in two
evaluations of a new HIV diagnostic testing algorithm--United States, 2011-2013.
PMID- 24355368
TI - Getting through together: an emergency physician's perspective on the February
2011 Christchurch earthquake.
PMID- 24355369
TI - Do more rules make us safer? Clinical decision rules, patient safety, and the
role of emergency physicians in health care: January 2014 Annals of Emergency
Medicine Journal Club.
PMID- 24355370
TI - Images in emergency medicine. A healthy young man with neck sprain.
Retropharyngeal tendonitis.
PMID- 24355372
TI - In reply.
PMID- 24355371
TI - Response to circulatory death determination in uncontrolled organ donors: a panel
viewpoint.
PMID- 24355373
TI - Ischemia complications after calcium channel blocker poisoning.
PMID- 24355374
TI - In reply.
PMID- 24355375
TI - Critical care management of verapamil and diltiazem overdose with a focus on
vasopressors: a 25-year experience at a single center.
PMID- 24355376
TI - Insulin for calcium channel toxicity.
PMID- 24355377
TI - In reply.
PMID- 24355378
TI - The study of potable water treatment process in Algeria (boudouaou station) -by
the application of life cycle assessment (LCA).
AB - Environmental impact assessment will soon become a compulsory phase in future
potable water production projects, in algeria, especially, when alternative
treatment processes such sedimentation ,coagulation sand filtration and
Desinfection are considered. An impact assessment tool is therefore developed for
the environmental evaluation of potable water production. in our study The
evaluation method used is the life cycle assessment (LCA) for the determination
and evaluation of potential impact of a drink water station ,near algiers (SEAL
Boudouaoua).LCA requires both the identification and quantification of materials
and energy used in all stages of the product's life, when the inventory
information is acquired, it will then be interpreted into the form of potential
impact " eco-indicators 99" towards study areas covered by LCA, using the
simapro6 soft ware for water treatment process is necessary to discover the
weaknesses in the water treatment process in order for it to be further improved
ensuring quality life. The main source shown that for the studied water treatment
process, the highest environmental burdens are coagulant preparation (30% for all
impacts), mineral resource and ozone layer depletion the repartition of the
impacts among the different processes varies in comparison with the other
impacts. Mineral resources are mainly consumed during alumine sulfate solution
preparation; Ozone layer depletion originates mostly from tetrachloromethane
emissions during alumine sulfate production. It should also be noted that,
despite the small doses needed, ozone and active Carbone treatment generate
significant impacts with a contribution of 10% for most of the impacts.Moreover
impacts of energy are used in producing pumps (20-25 GHC) for plant operation and
the unitary processes (coagulation, sand filtration decantation) and the most
important impacts are localized in the same equipment (40-75 GHC) and we can
conclude that:- Pre-treatment, pumping and EDR (EDR: 0.-6 0 kg CO2 eq. /produced
m3) are the process-units with higher environmental impacts.- Energy consumption
is the main source of impacts on climate change.- Chemicals consumption (e.g.
coagulants, oxidants) are the principle cause of impacts on the ozone layer
depletion.- Conventional plants: pre-treatment has high GHG emissions due to
chemicals consumption.
PMID- 24355379
TI - Development and evaluation of pictograms on medication labels for patients with
limited literacy skills in a culturally diverse multiethnic population.
AB - BACKGROUND: Much of the migrant workforce in Qatar is of low literacy level and
does not understand Arabic or English, presenting a significant challenge to
health care professionals. Medicine labels are typically in Arabic and English
and are therefore poorly understood by these migrant workers. OBJECTIVE: To
develop pictograms illustrating selected medicine label instructions and to
evaluate comprehension of the pictograms or conventional text supported with
verbal instructions in foreign workers with low literacy skills. METHODS: A range
of common labeling instructions were identified and pictograms depicting these
were developed using visual concepts and ideas from the literature. The process
involved a consultative approach with input from the researchers, a local graphic
artist, and members of the target population. The final set was evaluated for
comprehension in participants who were randomized to one of three study groups:
text plus verbal instructions, pictogram-only label, and pictogram with verbal
instructions. One-way ANOVA and Chi-square tests were used to assess differences
between group variables. Statistical significance was set at P <= 0.05. RESULTS:
Of 23 label instructions screened, 11 were selected for the study. A total of 123
participants took part in this study. Pictogram plus verbal instructions group
achieved better results in interpreting the majority of the label instructions (P
<= 0.05). The best interpreted pictograms with verbal instructions included:
"Take two tablets three times a day," "Take one tablet in the morning and one
tablet at night," and "Instill one drop in the eye." The worst interpreted
pictograms with verbal instructions were: "Do not take with dairy products" and
"Do not use by mouth." Some pictograms were difficult to interpret even when
accompanied with verbal instructions, suggesting the need to thoroughly pilot
them among users prior to implementation. CONCLUSION: Medication labels
consisting of simple pictorials supported by verbal instructions were better
comprehended by individuals with low literacy skills than labels with written
plus verbal instructions in a language that the individual did not understand.
Further, pictogram-only labels were the least comprehended types of medicine
labels among the participants.
PMID- 24355380
TI - Quality of psychopharmacological medication use in nursing home residents.
AB - BACKGROUND: Despite well-documented evidence regarding antipsychotic use in older
adults residing in nursing homes (NHs), there is a lack of evidence-based use and
quality benchmarks for other psychopharmacological medications (PPMs), including
antidepressants, anxiolytics, and sedative-hypnotics. OBJECTIVE: To estimate the
prevalence and patterns of use of PPMs and to measure the quality of PPM use.
METHODS: Using a 5% random sample of 2007 Medicare claims data linked to the
Minimum Data Set 2.0, this cross-sectional study identified a nationally
representative sample of 69,832 NH residents with >=3 months of
institutionalization. This study measured 1-year prevalence and quality of PPM
use, as assessed by indication, dose, and duration of use defined and
operationalized according to the current Centers for Medicare and Medicaid
Services Unnecessary Medication Guidance for Surveyors and relevant practice
guidelines. RESULTS: Over two-thirds of residents (72.1%, n=50,349) used >=1 PPM
in 2007, with the highest prevalence seen in antidepressants (59.4%), and the
lowest in anxiolytics (8.9%). Almost two-thirds (61.0%) of PPM users used >=2 PPM
classes. Compared to other PPM therapeutic classes, antipsychotic users had
greatest evidence of guideline adequate use by indication (95.8%) and dose
(78.7%). In addition, longer duration of adequate treatment was observed among
antipsychotic users (mean = 208 days, standard deviation [SD] = 118) as compared
to anxiolytic (mean = 159 days, SD = 118) and sedative-hypnotic users (mean = 183
days, SD = 117). CONCLUSIONS: This study found that PPM use remains highly
prevalent among long-stay Medicare NH residents. While antipsychotic use remained
high (31.5%), little antipsychotic use was deemed inadequate by indication.
However, the 1-year prevalence of use, dose, and duration of use of other PPMs
remain high and potentially inadequate. Practitioners and policy-makers should
heed both the high use and lower prescribing quality of antidepressants,
anxiolytics, and sedative-hypnotics in NH residents.
PMID- 24355381
TI - National antidepressant prescribing in children and adolescents with mental
health disorders after an FDA boxed warning.
AB - BACKGROUND: In October 2004, the U.S. Food and Drug Administration (FDA) issued a
boxed warning about an increased risk of suicidality (i.e., suicidal ideation,
behavior, or attempts) related to all antidepressants in children and
adolescents. OBJECTIVE: To describe national antidepressant prescribing patterns
in children and adolescents before, during, and after the introduction of the FDA
boxed warning. METHODS: Cross-sectional data from the 2002-2009 National
Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical
Care Survey (NHAMCS) were used to describe antidepressant prescribing patterns
within a nationally-representative sample of 4035 physician visits for children
and adolescents diagnosed with depression or other psychiatric disorder(s) [i.e.,
anxiety disorders or attention deficit/hyperactivity disorder (ADHD)]. RESULTS:
In 2002-2003, antidepressants were prescribed in 4.1 million (36.1%) visits,
followed by 3.2 million (28.8%) visits in 2004-2005 and 2.8 million (26.8%)
visits in 2006-2007. However, antidepressant prescribing patterns reversed during
2008-2009, with an increase to 3.6 million (32.5%) visits. Compared to the period
preceding the FDA boxed warning (2002-2003), a significant decline in visits
related to antidepressant prescribing detected in the immediate post-FDA boxed
warning period (2006-2007) (AOR = 0.67, 95% CI: 0.47-0.96). No association
between the FDA boxed warning and antidepressant prescribing visits was detected
during the FDA boxed warning period (2004-2005) (AOR = 0.80, 95% CI: 0.53-1.21)
and in the late post-FDA boxed warning period (2008-2009) (AOR = 1.01, 95% CI:
0.63-1.60). CONCLUSIONS: After a 2-year lag period, antidepressant prescribing
for visits of children and adolescents diagnosed with depression or other
psychiatric disorder(s) in community-based and outpatient clinic settings
declined when compared to the period preceding the FDA boxed warning. This
decline was not sustained in the period of five years after implementation of the
FDA boxed warning.
PMID- 24355382
TI - High-resolution mechanical imaging of the kidney.
AB - The objective of this study was to test the feasibility and reproducibility of in
vivo high-resolution mechanical imaging of the asymptomatic human kidney. Hereby
nine volunteers were examined at three different physiological states of urinary
bladder filling (a normal state, urinary urgency, and immediately after urinary
relief). Mechanical imaging was performed of the in vivo kidney using three
dimensional multifrequency magnetic resonance elastography combined with
multifrequency dual elastovisco inversion. Other than in classical elastography,
where the storage and loss shear moduli are evaluated, we analyzed the magnitude
|G(*)| and the phase angle phi of the complex shear modulus reconstructed by
simultaneous inversion of full wave field data corresponding to 7 harmonic drive
frequencies from 30 to 60Hz and a resolution of 2.5mm cubic voxel size.
Mechanical parameter maps were derived with a spatial resolution superior to that
in previous work. The group-averaged values of |G(*)| were 2.67+/-0.52kPa in the
renal medulla, 1.64+/-0.17kPa in the cortex, and 1.17+/-0.21kPa in the hilus. The
phase angle phi (in radians) was 0.89+/-0.12 in the medulla, 0.83+/-0.09 in the
cortex, and 0.72+/-0.06 in the hilus. All regional differences were significant
(P<0.001), while no significant variation was found in relation to different
stages of bladder filling. In summary our study provides first high-resolution
maps of viscoelastic parameters of the three anatomical regions of the kidney.
|G(*)| and phi provide novel information on the viscoelastic properties of the
kidney, which is potentially useful for the detection of renal lesions or
fibrosis.
PMID- 24355383
TI - Biosensor based on nanocomposite material for pathogenic virus detection.
AB - This paper introduces a DNA biosensor based on a DNA/chitosan/multi-walled carbon
nanotube nanocomposite for pathogenic virus detection. An easy, cost-effective
approach to the immobilization of probe DNA sequences on the sensor surface was
performed. Cyclic voltammograms were used to characterize the probe DNA sequence
immobilization. Complementary sequence hybridization was examined by
electrochemical impedance spectroscopy. Results revealed that the developed DNA
sensor can detect a target DNA concentration as low as 0.01*10(-12) M. The
sensitivity of the prepared sensor was 52.57 kOmega/fM. The reusability and
storage stability of the DNA sensor were also investigated. Results showed that
the electron-transfer resistance decreased to approximately 35% after 8 weeks and
to approximately 80% after 12 weeks of storage.
PMID- 24355384
TI - Influence of lecithin-lipid composition on physico-chemical properties of
nanoliposomes loaded with a hydrophobic molecule.
AB - In this work, we studied the effect of nanoliposome composition based on
phospholipids of docosahexaenoic acid (PL-DHA), salmon and soya lecithin, on
physico-chemical characterization of vector. Cinnamic acid was encapsulated as a
hydrophobic molecule in nanoliposomes made of three different lipid sources. The
aim was to evaluate the influence of membrane lipid structure and composition on
entrapment efficiency and membrane permeability of cinnamic acid. These
properties are important for active molecule delivery. In addition, size,
electrophoretic mobility, phase transition temperature, elasticity and membrane
fluidity were measured before and after encapsulation. The results showed a
correlation between the size of the nanoliposome and the entrapment. The
entrapment efficiency of cinnamic acid was found to be the highest in liposomes
prepared from salmon lecithin. The nanoliposomes composed of salmon lecithin
presented higher capabilities as a carrier for cinnamic acid encapsulation. These
vesicles also showed a high stability which in turn increases the membrane
rigidity of nanoliposome as evaluated by their elastic properties, membrane
fluidity and phase transition temperature.
PMID- 24355385
TI - Quantifying adhesion of acidophilic bioleaching bacteria to silica and pyrite by
atomic force microscopy with a bacterial probe.
AB - The adhesion of acidophilic bacteria to mineral surfaces is an important
phenomenon in bioleaching processes. In this study, functionalized colloidal
probes covered by bioleaching bacterial cells (Acidithiobacillus thiooxidans and
Leptospirillum ferrooxidans) were developed and used to sense specific adhesion
forces to a silica surface and a pyrite surface in various solutions.
Experimentally, recorded retraction curves of A. thiooxidans revealed sawtooth
features that were in good agreement with the wormlike chain model, while that of
L. ferrooxidans exhibited stair-step separation. The magnitudes of adhesion
forces and snap-off distances were strongly influenced by the ionic strength and
pH. Macroscopic surface properties including hydrophobicity and surface potential
for bacterial cells and substrata were measured by a sessile drop method and
microelectrophoresis. The ATR-FTIR spectra indicated the presence of different
types of biopolymers on two strains of bacteria.
PMID- 24355386
TI - Drugs for neuropathic pain.
PMID- 24355387
TI - The robotic surgery monopoly is a poor deal.
PMID- 24355388
TI - Volunteer doctors start a clinic for the marginalized of New York City.
PMID- 24355389
TI - Stop sitting on the fence: recommendations are essential to informed decision
making.
PMID- 24355390
TI - Lack of funding could undermine UK antibiotic resistance strategy, say experts.
PMID- 24355391
TI - Two Staffordshire hospitals to remain open under rescue plan.
PMID- 24355392
TI - Synthesis and biological evaluation of dehydroepiandrosterone-fused thiazole,
imidazo[2,1-b]thiazole, pyridine steroidal analogues.
AB - A series of steroidal[17,16-d]thiazole, steroidal[1,2-b]pyridine and
steroidal[17,16-d]thiazole[2,1-b]imidazo products were synthesized through a
convenient and productive method. Anti-proliferation activity against EC109
(human esophageal carcinoma), EC9706 (human esophageal carcinoma) and MGC-803
(human gastric carcinoma) cell lines was examined in vitro. Among the screened
compounds, several highly potential compounds were located.
PMID- 24355393
TI - Influence of phosphate and solution pH on the mobility of ZnO nanoparticles in
saturated sand.
AB - The mobility of nanoparticles (NPs) strongly depends on the chemical
characterization of the environmental medium. However, the influence of phosphate
on NPs mobility was ignored by scientists despite the serious phosphate
contamination in natural environments. Hence, the influence of phosphate and
solution pH on the mobility of zinc oxide nanoparticles (ZnO-NPs) was
investigated in water-saturated sand representative of groundwater aquifers,
which encompassed a range of P/Zn molar ratios (P/Zn: 0-4) and pH (4.8-10.0). The
transport of ZnO-NPs was dramatically enhanced in the presence of phosphate, even
at a low P/Zn molar ratio namely 0.25, and the retention of ZnO-NPs in the
saturated sand decreased with increasing P/Zn molar ratio. Moreover, attachment
efficiencies (alpha) and deposition rates (kd) of ZnO-NPs rapidly decreased with
increasing P/Zn molar ratio. In contrast, the solution pH had negligible effects
on ZnO-NP transport behavior under phosphate-abundant condition (P/Zn: 4). The
distinct effects may be explained by the energy interaction between ZnO-NPs and
sand surface under different conditions. Interestingly, under phosphate-abundant
condition (P/Zn: 4), solution pH could strongly affect the transport of Zn(2+) in
the water-saturated sand. Overall, this study outlines the importance of taking
account of phosphate into risk assessment of NPs in the environment.
PMID- 24355394
TI - Trace metal in surface water and groundwater and its transfer in a Yellow River
alluvial fan: evidence from isotopes and hydrochemistry.
AB - Metals are ubiquitous in the environment. The aim of sustainable management of
the agro-ecosystem includes ensuring that water continues to fulfill its function
in agricultural production, cycling of elements, and as a habitat of numerous
organisms. There is no doubt that the influence of large-scale irrigation
projects has impacted the regional surface-groundwater interactions in the North
China Plain (NCP). Given these concerns, the aim of this study is to evaluate the
pollution, identify the sources of trace metals, analyze the influence of surface
groundwater interactions on trace metal distribution, and to propose urgent
management strategies for trace metals in the agriculture area in China. Trace
metals, hydrochemical indicators (EC, pH, concentrations of Na(+), K(+), Mg(2+),
Ca(2+), Cl(-), SO4(2-), and HCO3(-)) and stable isotopic composition (delta(18)O
and delta(2)H) were determined for surface water (SW) and groundwater (GW)
samples. Trace metals were detected in all samples. Concentrations of Fe, Se, B,
Mn, and Zn in SW exceeded drinking water standards by 14.8%, 29.6%, 25.9%, 11.1%,
and 14.8% higher, respectively, and by 3.8%, 23.1%, 11.5%, 11.5%, and 7.7% in GW.
The pollution of trace metals in surface water was more serious than that in
groundwater, and was also higher than in common irrigation areas in NCP. Trace
metals were found to have a combined origin of geogenic and agriculture and
industrial activities. Their distribution varied greatly and exhibited a certain
relationship with the water flow direction, with the exception of a number of
singular sites. Hydrochemical and environmental isotopic evidence indicates
surface-groundwater interactions influence the spatial distribution of trace
metal in the study area. Facing the ongoing serious pollution, management
practices for source control, improved control technologies, and the construction
of a monitoring net to warn of increased risk are urgently needed.
PMID- 24355395
TI - Delving into the environmental aspect of a Sardinian white wine: from partial to
total life cycle assessment.
AB - The aim of this study was to deepen the assessment of the environmental impacts
of a white wine produced in Sardinia (FU 750 ml), performing an attributional
LCA. The system boundaries were extended, from 'cradle to gate' (partial LCA) of
a previous study, to 'cradle to grave' (total LCA), in order to identify the
environmental impacts occurring along the wine life cycle stages (vine planting,
grape production, wine production, bottling and packaging, distribution, final
disposal of the glass bottle). Some assumptions were made in order to quantify
the environmental impact of the transportation phase, regarding the few data
which were available. Inventory data were mainly collected through direct
communication with the Company involved in the study. Results showed that the
environmental performance of wine was mostly determined by the glass bottle
production (for all impact categories except ozone layer depletion). The second
contributor was the agricultural phase, which included two sub-phases: vine
planting and grape production. Results showed that the vine planting sub-phase
was not negligible given its contribution to the agricultural phase, mainly due
to diesel fuel consumption. Transportation impact was found to be relevant for
long distance distribution (USA); the impact categories more affected by
transport were acidification, eutrophication, photochemical oxidation and global
warming potential. Suggested opportunities to reduce the overall environmental
impact were the introduction of a lighter glass bottle or the substitution of the
glass bottle with a polylaminate container.
PMID- 24355396
TI - Routine screening of harmful microorganisms in beach sands: implications to
public health.
AB - Beaches worldwide provide recreational opportunities to hundreds of millions of
people and serve as important components of coastal economies. Beach water is
often monitored for microbiological quality to detect the presence of indicators
of human sewage contamination so as to prevent public health outbreaks associated
with water contact. However, growing evidence suggests that beach sand can harbor
microbes harmful to human health, often in concentrations greater than the beach
water. Currently, there are no standards for monitoring, sampling, analyzing, or
managing beach sand quality. In addition to indicator microbes, growing evidence
has identified pathogenic bacteria, viruses, and fungi in a variety of beach
sands worldwide. The public health threat associated with these populations
through direct and indirect contact is unknown because so little research has
been conducted relating to health outcomes associated with sand quality. In this
manuscript, we present the consensus findings of a workshop of experts convened
in Lisbon, Portugal to discuss the current state of knowledge on beach sand
microbiological quality and to develop suggestions for standardizing the
evaluation of sand at coastal beaches. The expert group at the "Microareias 2012"
workshop recommends that 1) beach sand should be screened for a variety of
pathogens harmful to human health, and sand monitoring should then be initiated
alongside regular water monitoring; 2) sampling and analysis protocols should be
standardized to allow proper comparisons among beach locations; and 3) further
studies are needed to estimate human health risk with exposure to contaminated
beach sand. Much of the manuscript is focused on research specific to Portugal,
but similar results have been found elsewhere, and the findings have worldwide
implications.
PMID- 24355397
TI - Transcriptome profiling in engrailed-2 mutant mice reveals common molecular
pathways associated with autism spectrum disorders.
AB - BACKGROUND: Transcriptome analysis has been used in autism spectrum disorder
(ASD) to unravel common pathogenic pathways based on the assumption that distinct
rare genetic variants or epigenetic modifications affect common biological
pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took
advantage of the En2-/- mouse model and performed transcriptome profiling on
cerebellar and hippocampal adult tissues. METHODS: Cerebellar and hippocampal
tissue samples from three En2-/- and wild type (WT) littermate mice were assessed
for differential gene expression using microarray hybridization followed by
RankProd analysis. To identify functional categories overrepresented in the
differentially expressed genes, we used integrated gene-network analysis, gene
ontology enrichment and mouse phenotype ontology analysis. Furthermore, we
performed direct enrichment analysis of ASD-associated genes from the SFARI
repository in our differentially expressed genes. RESULTS: Given the limited
number of animals used in the study, we used permissive criteria and identified
842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/-
hippocampus. Our functional analysis revealed that the molecular signature of En2
/- cerebellum and hippocampus shares convergent pathological pathways with ASD,
including abnormal synaptic transmission, altered developmental processes and
increased immune response. Furthermore, when directly compared to the repository
of the SFARI database, our differentially expressed genes in the hippocampus
showed enrichment of ASD-associated genes significantly higher than previously
reported. qPCR was performed for representative genes to confirm relative
transcript levels compared to those detected in microarrays. CONCLUSIONS: Despite
the limited number of animals used in the study, our bioinformatic analysis
indicates the En2-/- mouse is a valuable tool for investigating molecular
alterations related to ASD.
PMID- 24355398
TI - Amniocentesis for fetal lung maturity testing.
PMID- 24355399
TI - Reply: To PMID 24139938.
PMID- 24355400
TI - RORB gene and 9q21.13 microdeletion: report on a patient with epilepsy and mild
intellectual disability.
AB - Copy number variants represent an important cause of neurodevelopmental disorders
including epilepsy, which is genetically determined in 40% of cases. Epilepsy is
caused by chromosomal imbalances or mutations in genes encoding subunits of
neuronal voltage- or ligand-gated ion channels or proteins related to neuronal
maturation and migration during embryonic development. Here, we report on a girl
with mild intellectual disability and idiopathic partial epilepsy. Array-CGH
analysis showed a 1.040 Mb de novo interstitial deletion at 9q21.13 band
encompassing only four genes, namely RORB, TRPM6, NMRK1, OSTF1, two open reading
frames (C9orf40, C9orf41), and a microRNA (MIR548H3). RORB encodes a nuclear
receptor highly expressed in the retina, cortex, and thalamus. We hypothesize its
role in producing the phenotype of our patient and compare this case with other
ones previously reported in the literature to better identify a genotype
phenotype correlation.
PMID- 24355401
TI - Who benefits from extended continuing care for cocaine dependence?
AB - The goal of this study was to determine which cocaine dependent patients engaged
in an intensive outpatient program (IOP) were most likely to benefit from
extended continuing care (24 months). Participants (N=321) were randomized to:
IOP treatment as usual (TAU), TAU plus Telephone Monitoring and Counseling (TMC),
or TAU plus TMC plus incentives for session attendance (TMC+). Potential
moderators examined were gender, stay in a controlled environment prior to IOP,
number of prior drug treatments, and seven measures of progress toward IOP goals.
Outcomes were: (1) abstinence from all drugs and heavy alcohol use, and (2)
cocaine urine toxicology. Follow-ups were conducted at 3, 6, 9, 12, 18, and 24
months post-baseline. Results indicated that there were significant effects
favoring TMC+ over TAU on the cocaine urine toxicology outcome for participants
in a controlled environment prior to IOP and for those with no days of depression
early in IOP. Trends were obtained favoring TMC over TAU for those in a
controlled environment (cocaine urine toxicology outcome) or with high
family/social problem severity (abstinence composite outcome), and TMC+ over TAU
for those with high family/social problem severity or high self-efficacy (cocaine
urine toxicology outcome). None of the other potential moderator effects examined
reached the level of a trend. These results generally do not suggest that
patients with greater problem severity or poorer performance early in treatment
on the measures considered in this report will benefit to a greater degree from
extended continuing care.
PMID- 24355402
TI - Regulation of photosynthetic performance and antioxidant capacity by 60Co gamma
irradiation in Zizania latifolia plants.
AB - The aim of the present work was to investigate the photosynthetic performance and
antioxidant enzyme activities in response to gamma-irradiation of an aquatic
plant Zizania latifolia. The Z. latifolia seedlings at 6-leaf stage were exposed
to 25, 50 and 100 Gy of gamma rays from a (60)Co source. The growth parameters,
chlorophyll contents, photosynthetic gas exchange, chlorophyll fluorescence,
malondialdehyde (MDA) content, antioxidant enzyme activities and antioxidant
contents were examined at 1-5 weeks post-irradiation (WPI). The results showed
that plant height, leaf number and tiller (branch close to ground) number were
significantly suppressed by 50 and 100 Gy irradiation at 5, 3-5 and 4-5 WPI,
respectively, but they were not significantly different from control by 25 Gy
irradiation. Chlorophyll a, chlorophyll b, and total chlorophyll contents were
also found to be significantly decreased by irradiation. The net photosynthetic
rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci) and
transpiration rate (Tr) generally declined in a dose-dependent manner. As for the
chlorophyll fluorescence parameters, maximum quantum efficiency of PSII
photochemistry (Fv/Fm), actual photochemical efficiency of PSII (Phi(PSII)) and
photochemical quenching (qP) were observed to be significantly decreased compared
to the control at 3 WPI, while non-photochemical quenching (NPQ) significantly
increased by 100 Gy. gamma-irradiation induced substantial increase in MDA
content, ascorbate peroxidase (APX) activity, reduced ascorbate (AsA) content and
reduced glutathione (GSH) content, suggesting a protective mechanism of Z.
latifolia plant against oxidative stress when exposed to gamma-irradiation.
PMID- 24355403
TI - Supplementation with omega-3 fatty acids during gestation and lactation to a
vitamin B12-deficient or -supplemented diet improves pregnancy outcome and
metabolic variables in Wistar rats.
AB - Maternal vitamin B12 deficiency leads to an adverse pregnancy outcome and
increases the risk for developing diabetes and metabolic syndrome in mothers in
later life. Our earlier studies have demonstrated that vitamin B12 and n-3
polyunsaturated fatty acids (PUFA) are interlinked in the one carbon cycle. The
present study for the first time examines the effect of maternal n-3 PUFA
supplementation to vitamin B12 deficient or supplemented diets on pregnancy
outcome, fatty-acid status and metabolic variables in Wistar rats. Pregnant dams
were assigned to one of the following groups: control, vitamin B12 deficient,
vitamin B12 supplemented, vitamin B12 deficient + n-3 PUFA or vitamin B12
supplemented + n-3 PUFA. The amount of vitamin B12 in the supplemented group was
0.50 MUg kg(-1) diet and n-3 PUFA was alpha linolenic acid (ALA) 1.68,
eicosapentaenoic acid 5.64, docosahexaenoic acid (DHA) 3.15 (g per 100g fatty
acids per kg diet). Our findings indicate that maternal vitamin B12
supplementation did not affect the weight gain of dams during pregnancy but
reduced litter size and weight and was ameliorated by n-3 PUFA supplementation.
Vitamin B12 deficiency or supplementation resulted in a low percentage
distribution of plasma arachidonic acid and DHA. n-3 PUFA supplementation to
these diets improved the fatty-acid status. Vitamin B12 deficiency resulted in
higher homocysteine and insulin levels, which were normalised by supplementation
with either vitamin B12 or n-3 PUFA. Our study suggests that maternal vitamin B12
status is critical in determining pregnancy outcome and metabolic variables in
dams and that supplementation with n-3 PUFA is beneficial.
PMID- 24355404
TI - Floral scent in natural hybrids of Ipomopsis (Polemoniaceae) and their parental
species.
AB - BACKGROUND AND AIMS: Floral traits, such as floral volatiles, can contribute to
pre-zygotic reproductive isolation by promoting species-specific pollinator
foraging. When hybrid zones form, floral traits could also influence post-zygotic
isolation. This study examined floral volatiles in parental species and natural
hybrids in order to explore potential scent mediation of pre-zygotic and post
zygotic isolation. METHODS: Floral bouquets were analysed for the sister species
Ipomopsis aggregata and I. tenuituba and their natural hybrids at two contact
sites differing in both hybridization rate and temporal foraging pattern of
hawkmoth pollinators. Floral volatiles were quantified in diurnal and nocturnal
scent samples using gas chromatography-mass spectrometry. KEY RESULTS: The
bouquets of parental species and hybrids showed qualitative overlap. All flowers
emitted similar sets of monoterpenoid, sesquiterpenoid, aliphatic and benzenoid
compounds, but separated into groups defined by multivariate analysis of
quantitative emissions. The parental species differed most strikingly in the
nitrogenous compound indole, which was found almost exclusively in nocturnal
bouquets of I. tenuituba. Natural hybrid bouquets were highly variable, and
showed emission rates of several compounds that appeared transgressive. However,
indole emission rates were intermediate in the hybrids compared with rates in the
parents. Volatile bouquets at the contact site with lower hybridization did not
show greater species specificity in overall scent emission, but I. tenuituba
presented a stronger indole signal during peak hawkmoth activity at that site.
CONCLUSIONS: The two species of Ipomopsis differed in patterns of floral
bouquets, with indole emitted in nocturnal I. tenuituba, but not in I. aggregata.
Natural hybrid bouquets were not consistently intermediate between the parents,
although hybrids were intermediate in indole emission. The indole signal could
potentially serve as a hawkmoth attractant that mediates reproductive isolation
both before and after hybrid formation.
PMID- 24355405
TI - Phenoloxidase from the sea cucumber Apostichopus japonicus: cDNA cloning,
expression and substrate specificity analysis.
AB - Phenoloxidase (PO) is a crucial component of the immune system of echinoderms. In
the present study, the full-length cDNA of PO (AjPO) was cloned from coelomocytes
of the sea cucumber Apostichopus japonicus using 3'- and 5'-rapid amplification
of cDNA ends (RACE) PCR method, which is 2508 bp, with an open reading frame
(ORF) of 2040 bp encoding 679 amino acids. AjPO contains a transmembrane domain,
and three Cu-oxidase domains with copper binding centers formed by 10 histidines,
one cysteine and one methionine respectively. Phylogenetic analysis revealed that
AjPO was clustered with laccase-type POs of invertebrates. Using the isolated
membrane proteins as crude AjPO, the enzyme could catalyze the substrates
catechol, L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine and hydroquinone, but
failed to oxidize tyrosine. The results described above collectively proved that
AjPO was a membrane-binding laccase-type PO. The quantitative real-time PCR (qRT
PCR) analysis revealed that AjPO mRNA was expressed in muscle, body wall,
coelomocytes, tube feet, respiratory tree and intestine with the highest
expression level in coelomocytes. AjPO could be significantly induced by
lipopolysaccharide (LPS), peptidoglycan (PGN), Zymosan A and polyinosinic
polycytidylic acid (PolyI:C), suggesting AjPO is closely involved in the defense
against the infection of bacteria, fungi and double-stranded RNA viruses.
PMID- 24355406
TI - The physiological performance and immune responses of juvenile Amur sturgeon
(Acipenser schrenckii) to stocking density and hypoxia stress.
AB - Stocking density and hypoxia are considered priority issues in aquaculture
research. In this study, two experiments were carried out in order to investigate
the effects of chronic stress (stocking density) and acute stress (hypoxia) on
the immune physiology responses (hematology, serum cortisol, glucose, total
protein and the mRNA expression of CYP 1A) of juvenile Amur sturgeon (Acipenser
schrenckii). In the chronic stress study, three triplicate groups of Amur
sturgeon (42.0 +/- 2.3 g) were reared in nine square concrete ponds (4.4 * 4.4 *
0.45 m3) at three stocking densities (3.7, 6.9 and 9.0 kg/m3) for 50 days. In the
acute stress study, three triplicate groups: normal group (7 mg/l), hypoxia group
1 (5 mg/l) and hypoxia group 2 (3 mg/l) were used in nine 100 L indoor tanks.
Sampling was performed at the end of the stocking density experiment (50 days)
and at 0, 0.5, 1.5, 3 and 6 h after hypoxia stress. The results showed that
increased stocking density reduced the morphological indexes (hepatosomatic
index, spleen-somatic index and kidney-somatic index), while total protein and
hemoglobin increased significantly in the stressed group. In response to hypoxia,
the levels of cortisol, glucose and hematological parameters elevated
significantly after this stress. As for spleen-somatic index, there was a decline
after hypoxia though H1 group returned to the normal level at 3 h and 6 h after
hypoxia stress. Additionally, In order to better understand the immune response
of Amur sturgeon to chronic and acute stressors, we cloned the complete coding
sequence of Amur sturgeon CYP 1A for the first time and investigated its tissue
specific expression and stress-induced expression. CYP 1A mRNA in liver showed
over expressions both in crowding condition and in hypoxia stress. The same trend
was also found in spleen and kidney which may provide evidence that CYP 1A could
serve as a good indicator of immune response in Amur sturgeon. In addition, the
result suggested a typical immune response both in high stocking density and
hypoxia stress. But the chronically stressed fish might have an adaptation
capability to survive under a stable crowding condition without a change in some
immune parameters (cortisol, glucose, WBCs and RBCs).
PMID- 24355407
TI - Comparison of clinicopathological characteristics and prognosis between early and
late recurrence after curative surgery for colorectal cancer.
AB - BACKGROUND: Despite curative surgery for colorectal cancer, some patients
experience tumor recurrence. Whether early recurrence is associated with a
shorter postrecurrence survival period compared with late recurrence remains
unknown. METHODS: A total of 395 patients with tumor recurrence after curative
surgery for colorectal cancer were enrolled and divided into early (<3 years) and
late (>=3 years) recurrence groups. Clinicopathologic characteristics, recurrence
patterns, and postrecurrence survival were compared. RESULTS: For stage I and II
colorectal cancer, patients with T4 lesions tended to experience early
recurrence. For stage III colorectal cancer, early recurrence was more common in
patients with N2 disease. Patients with older age, mucinous-type tumors, poorly
differentiated histology, the presence of lymphovascular invasion, or multiple
site recurrence tended to die <2 years after recurrence. Median postrecurrence
survival was similar for the 2 groups. Patients undergoing resection of liver or
lung metastases demonstrated longer postrecurrence survival compared with those
who did not undergo resection. CONCLUSIONS: Compared with late recurrence, early
recurrence does not indicate a worse outcome in colorectal cancer.
PMID- 24355408
TI - Cutaneous manifestations of anti-angiogenic therapy in oncology: Review with
focus on VEGF inhibitors.
AB - The role of the VEGF signaling pathway in angiogenesis has been extensively
investigated, and many new targeted anti-angiogenic drugs have evolved from this
knowledge. The recent approval and introduction of these anti-neoplastic drugs
has revolutionized the treatment of many types of cancers, but has also revealed
numerous toxicities to the skin and its adnexae. Since these cutaneous side
effects may have a significant impact on the physical, emotional and psychosocial
health of patients, it is important for dermatologists and oncologists alike to
be aware of the cutaneous complications of these drugs in order to properly
diagnose and treat them. This review will detail the presentation of the
cutaneous complications of the anti-angiogenic drugs, most notably bevacizumab,
sorafenib and sunitinib, and shed light on the management of such adverse
reactions.
PMID- 24355409
TI - Targeting the MET gene for the treatment of non-small-cell lung cancer.
AB - Recently, a better understanding of the specific mechanisms of oncogene addiction
has led to the development of antitumor strategies aimed at blocking these
abnormalities in different malignancies, including lung cancer. These
abnormalities trigger constitutive activation of tyrosine kinase receptors (RTKs)
involved in fundamental cell mechanisms such as proliferation, survival,
differentiation and migration, and consequently the aberrant signaling of RTKs
leads to cancer growth and survival. The inhibition of aberrant RTKs and
downstream signaling pathways has opened the door to the targeted therapy era. In
non-small-cell lung cancer (NSCLC), molecular research has allowed the
discrimination of different aberrant RTKs in lung cancer tumorigenesis and
progression, and thus the identification of several targetable oncogenic drivers.
Following the development of small molecules (gefitinib/erlotinib and crizotinib)
able to reversibly inhibit the epidermal growth factor receptor (EGFR) and
signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively,
the MET signaling pathway has also been recognized as a potential target.
Moreover, according to current knowledge, MET could be considered both as a
secondary oncogenic mechanism and as a prognostic factor. Several therapeutic
strategies for inhibiting activated hepatocyte growth factor receptor (HGFR) and
the subsequent downstream signaling transduction have been improved in order to
block tumor growth. This review will focus on the MET pathway and its role in
resistance to EGFR TK (tyrosine kinase) inhibitors, the different strategies of
its inhibition, and the potential approaches to overcoming acquired resistance.
PMID- 24355411
TI - Clinical characteristics of chemotherapy-induced alopecia in childhood.
AB - BACKGROUND: Chemotherapy-induced alopecia (CIA) is a frequent complication in
patients with cancer. There are an increasing number of reports of permanent CIA.
OBJECTIVE: We investigated the clinical characteristics of CIA, including
permanent CIA in childhood. METHODS: We collected data on 159 pediatric patients
who had undergone high-dose conditioning chemotherapy followed by hematopoietic
stem cell transplantation and 167 control subjects, using a questionnaire,
medical record reviews, and phototrichograms. RESULTS: Alopecia began at 1.5 +/-
1.4 months and was sustained until 2.2 +/- 1.6 months after chemotherapy
initiation. Hair regrowth started 2.6 +/- 1.6 months after chemotherapy ceased
and lasted for 7.3 +/- 4.9 months. The mean hair density and thickness were 198.3
+/- 47.4/cm(2) and 76.3 +/- 18.4 MUm in the patient group and 229.6 +/-
34.5/cm(2) and 79.5 +/- 12.4 MUm in the control group, respectively (both, P <
.001). In all, 19 (12%) patients experienced permanent CIA. Thiotepa use was
identified as a significant risk factor for permanent CIA (odds ratio 7.57, P =
.002). LIMITATIONS: Cross-sectional study in a single-center is a limitation.
CONCLUSION: CIA is common in pediatric patients. Use of thiotepa is strongly
associated with permanent CIA.
PMID- 24355413
TI - Risk assessment for cardiovascular and respiratory mortality due to air pollution
and synoptic meteorology in 10 Canadian cities.
AB - Synoptic weather and ambient air quality synergistically influence human health.
We report the relative risk of mortality from all non-accidental, respiratory-,
and cardiovascular-related causes, associated with exposure to four air
pollutants, by weather type and season, in 10 major Canadian cities for 1981
through 1999. We conducted this multi-city time-series study using Poisson
generalized linear models stratified by season and each of six distinctive
synoptic weather types. Statistically significant relationships of mortality due
to short-term exposure to carbon monoxide, nitrogen dioxide, sulphur dioxide, and
ozone were found, with significant modifications of risk by weather type, season,
and mortality cause. In total, 61% of the respiratory-related mortality relative
risk estimates were significantly higher than for cardiovascular-related
mortality. The combined effect of weather and air pollution is greatest when
tropical-type weather is present in the spring or summer.
PMID- 24355414
TI - Performance of single mechanoluminescent particle as ubiquitous light source.
AB - In this study, we have investigated mechanoluminescent (ML) performance of single
ML particle as ubiquitous light source. When using high-speed CCD camera with
image intensifier and microscopic equipment, mechanoluminescence from single
particle was observed. As to the quantitative ML evaluation of the single ML
particle was carried out using photomultiplier, and successfully estimated the
performance of the single ML particle as an intensity controllable light source
in nW order.
PMID- 24355412
TI - Systemic dexmedetomidine augments inhibitory synaptic transmission in the
superficial dorsal horn through activation of descending noradrenergic control:
an in vivo patch-clamp analysis of analgesic mechanisms.
AB - alpha2-Adrenoceptors are widely distributed throughout the central nervous system
(CNS) and the systemic administration of alpha2-agonists such as dexmedetomidine
produces clinically useful, centrally mediated sedation and analgesia; however,
these same actions also limit the utility of these agents (ie, unwanted sedative
actions). Despite a wealth of data on cellular and synaptic actions of alpha2
agonists in vitro, it is not known which neuronal circuits are modulated in vivo
to produce the analgesic effect. To address this issue, we made in vivo
recordings of membrane currents and synaptic activities in superficial spinal
dorsal horn neurons and examined their responses to systemic dexmedetomidine. We
found that dexmedetomidine at doses that produce analgesia (<10 MUg/kg) enhanced
inhibitory postsynaptic transmission within the superficial dorsal horn without
altering excitatory synaptic transmission or evoking direct postsynaptic membrane
currents. In contrast, higher doses of dexmedetomidine (>10 MUg/kg) induced
outward currents by a direct postsynaptic action. The dexmedetomidine-mediated
inhibitory postsynaptic current facilitation was not mimicked by spinal
application of dexmedetomidine and was absent in spinalized rats, suggesting that
it acts at a supraspinal site. Furthermore, it was inhibited by spinal
application of the alpha1-antagonist prazosin. In the brainstem, low doses of
systemic dexmedetomidine produced an excitation of locus coeruleus neurons. These
results suggest that systemic alpha2-adrenoceptor stimulation may facilitate
inhibitory synaptic responses in the superficial dorsal horn to produce analgesia
mediated by activation of the pontospinal noradrenergic inhibitory system. This
novel mechanism may provide new targets for intervention, perhaps allowing
analgesic actions to be dissociated from excessive sedation.
PMID- 24355415
TI - Challenges of conducting experimental studies within a clinical nursing context.
AB - In recent years, several distinguished scholars have advocated for nursing
research that may carry strong evidence for practice. Their advocacy have
highlighted that nursing science has reached a point where as nurse researchers
we need to develop the questions we ask and design studies that have the power to
produce solid, translational, evidence-based knowledge. To do so, we need to
carry out experimental tests on complex, everyday nursing interventions and
activities. We also need to create public space to present accounts of our
endeavours pursuing this type of design in clinical practice. This paper will
discuss some of the most important insights gained from conducting a quasi
experimental study in which the aim was to investigate the effect of a theory
based intervention, targeting knowledge and attitudes among registered nurses
regarding cancer pain management. The importance of careful practical and
methodological planning is emphasised, and the need for participation-friendly
interventions is discussed.
PMID- 24355416
TI - HBV-related health behaviors in a socio-cultural context: perspectives from
Khmers and Koreans.
AB - PURPOSE: The aim of this study is to explore factors influencing health and
health care within the sociocultural context of Cambodian Americans (CAs or
Khmers) and Korean Americans (KA) and to examine intergroup similarities and
differences between CAs and KAs, focusing on hepatitis B virus (HBV) and liver
cancer prevention behaviors. METHODS: The study used a qualitative design guided
by the revised Network Episode Model (NEM) and informed by ethnographic analysis.
Focus group interviews with key informants among CA community health leaders
(CHLs, n=14) and individual interviews with key informants of KA CHLs (n=9) were
audiotaped and transcribed. RESULTS: Three categories that influenced HBV and
liver cancer prevention emerged from both CAs and KAs: the socio-cultural,
individual, and behavioral. Four additional subcategories (sub-themes) of
sociocultural were identified as socio-history, socio-medicine, socio-linguistic,
and socio-health resources. Both CAs and KAs, however, have low levels of
knowledge and significant misunderstandings about HBV infection. CONCLUSIONS: The
study identifies and compares the social-cultural determinant for HBV and liver
cancer and highlights the factors of education, intercultural communication, and
interactions within socio-cultural contexts of CA and KA subgroups. In general,
conceptual overlaps are apparent between Khmers (from now on, the terms, CA and
Khmer, will be used interchangeably) and Koreans except for the sub-theme of
socio-history. However, differences in concept-specific attributes point to the
need to account for differing conceptualizations and implications of specific
ethnic groups' sociocultural contexts, and to design contextually-relevant
outreach and educational interventions for targeted AAPI subgroups.
PMID- 24355417
TI - Resourcefulness training intervention: a promising approach to improve mental
health of mothers with technology-dependent children.
AB - The population of children dependent on medical technology such as mechanical
ventilation, feeding tubes, and supplemental oxygen continues to grow in the
United States. These children are frequently cared for by their mothers at home
following hospital discharge. Research indicates that these mothers are at high
risk for negative mental health outcomes that affect both caregiver and care
recipient. The purpose of this randomized controlled pilot trial was to determine
the feasibility, acceptability, and efficacy of resourcefulness training (RT), a
cognitive-behavioral intervention, among mothers of technology-dependent
children. RT was found to be a feasible and acceptable intervention with this
population during the 6 week study. The effect size in this pilot study
demonstrates initial efficacy and indicates areas for strengthening the
intervention protocol. RT is a promising intervention that can be employed by
pediatric nurses to assist mothers in the home management of technology-dependent
children.
PMID- 24355418
TI - Cisplatin-ineligible and chemotherapy-ineligible patients should be the focus of
new drug development in patients with advanced bladder cancer.
PMID- 24355410
TI - Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis:
results from the Italian Psocare registry.
AB - BACKGROUND: Some studies have shown that switching patients from one tumor
necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have
an inadequate response or an adverse event. OBJECTIVE: We sought to assess the
variables predicting the efficacy of the second TNF-alfa inhibitor in patients
discontinuing the first TNF-alfa inhibitor. METHODS: Data from all 5423
consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between
September 2005 and September 2010 who were included in the Italian Psocare
registry were analyzed. RESULTS: In 105 patients who switched to a second TNF
alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis
Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by
45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy
(loss of initial PASI 75 response) or adverse events/intolerance were more likely
to reach PASI 75 than those who switched as a result of primary inefficacy (PASI
75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard
ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). LIMITATIONS:
There was a small number of patients with complete follow-up data. CONCLUSION:
PASI 75 response in patients who switched from one anti-TNF-alfa agent to another
was significantly reduced in patients who showed primary inefficacy of the first
anti-TNF-alfa.
PMID- 24355419
TI - TCDD dysregulation of 13 AHR-target genes in rat liver.
AB - Despite several decades of research, the complete mechanism by which 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD) and other xenobiotic agonists of the aryl
hydrocarbon receptor (AHR) cause toxicity remains unclear. While it has been
shown that the AHR is required for all major manifestations of toxicity, the
specific downstream changes involved in the development of toxic phenotypes
remain unknown. Here we examine a panel of 13 genes that are AHR-regulated in
many species and tissues. We profiled their hepatic mRNA abundances in two rat
strains with very different sensitivities to TCDD: the TCDD-sensitive Long-Evans
(Turku/AB; L-E) and the TCDD-resistant Han/Wistar (Kuopio; H/W). We evaluated
doses ranging from 0 to 3000MUg/kg at 19h after TCDD exposure and time points
ranging from 1.5 to 384h after exposure to 100MUg/kg TCDD. Twelve of 13 genes
responded to TCDD in at least one strain, and seven of these showed statistically
significant inter-strain differences in the time course analysis (Aldh3a1,
Cyp1a2, Cyp1b1, Cyp2a1, Fmo1, Nfe2l2 and Nqo1). Cyp2s1 did not respond to TCDD in
either rat strain. Five genes exhibited biphasic responses to TCDD insult (Ahrr,
Aldh3a1, Cyp1b1, Nfe2l2 and Nqo1), suggesting a secondary event, such as
association with additional transcriptional modulators. Of the 12 genes that
responded to TCDD during the dose-response analysis, none had an ED50 equivalent
to that of Cyp1a1, the most sensitive gene in this study, while nine genes
responded to doses at least 10-100 fold higher, in at least one strain (Ahrr (L
E), Aldh3a1 (both), Cyp1a2 (both), Cyp1b1 (both), Cyp2a1 (L-E), Inmt (both),
Nfe2l2 (L-E), Nqo1 (L-E) and Tiparp (both)). These data shed new light on the
association of the AHR target genes with TCDD toxicity, and in particular the
seven genes exhibiting strain-specific differences represent strong candidate
mediators of Type-II toxicities.
PMID- 24355420
TI - Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression
induced by PCB 126 in human skin and liver-derived cell lines.
AB - The aryl hydrocarbon receptor (AhR) is an important mediator of toxic responses
after exposure to xenobiotics including 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) and dioxin-like polychlorinated biphenyls (PCBs). Activation of AhR
responsive genes requires AhR dimerization with the aryl hydrocarbon receptor
nuclear translocator (ARNT), a heterodimeric partner also shared by the hypoxia
inducible factor-1alpha (HIF-1alpha) protein. TCDD-stimulated AhR transcriptional
activity can be influenced by hypoxia; however, it less well known whether
hypoxia interferes with AhR transcriptional transactivation in the context of PCB
mediated AhR activation in human cells. Elucidation of this interaction is
important in liver hepatocytes which extensively metabolize ingested PCBs and
experience varying degrees of oxygen tension during normal physiologic function.
This study was designed to assess the effect of hypoxia on AhR transcriptional
responses after exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126). Exposure
to 1% O2 prior to PCB 126 treatment significantly inhibited CYP1A1 mRNA and
protein expression in human HepG2 and HaCaT cells. CYP1A1 transcriptional
activation was significantly decreased upon PCB 126 stimulation under conditions
of hypoxia. Additionally, hypoxia pre-treatment reduced PCB 126 induced AhR
binding to CYP1 target gene promoters. Importantly, ARNT overexpression rescued
cells from the inhibitory effect of hypoxia on XRE-luciferase reporter activity.
Therefore, the mechanism of interference of the signaling crosstalk between the
AhR and hypoxia pathways appears to be at least in part dependent on ARNT
availability. Our results show that AhR activation and CYP1A1 expression induced
by PCB 126 were significantly inhibited by hypoxia and hypoxia might therefore
play an important role in PCB metabolism and toxicity.
PMID- 24355421
TI - An oligofluorene truxene based distributed feedback laser for biosensing
applications.
AB - The first example of an all-organic oligofluorene truxene based distributed
feedback laser for the detection of a specific protein-small molecule interaction
is reported. The protein avidin was detected down to 1 MUg mL(-1) using our
biotin-labelled biosensor platform. This interaction was both selective and
reversible when biotin was replaced with desthiobiotin. Avidin detection was not
perturbed by Bovine Serum Albumin up to 50,000 MUg mL(-1). Our biosensor offers a
new detection platform that is both highly sensitive, modular and potentially re
usable.
PMID- 24355422
TI - Acute microcirculatory effects of medium frequency versus high frequency
neuromuscular electrical stimulation in critically ill patients - a pilot study.
AB - BACKGROUND: Intensive care unit-acquired weakness (ICUAW) is a common
complication, associated with significant morbidity. Neuromuscular electrical
stimulation (NMES) has shown promise for prevention. NMES acutely affects
skeletal muscle microcirculation; such effects could mediate the favorable
outcomes. However, optimal current characteristics have not been defined. This
study aimed to compare the effects on muscle microcirculation of a single NMES
session using medium and high frequency currents. METHODS: ICU patients with
systemic inflammatory response syndrome (SIRS) or sepsis of three to five days
duration and patients with ICUAW were studied. A single 30-minute NMES session
was applied to the lower limbs bilaterally using current of increasing intensity.
Patients were randomly assigned to either the HF (75 Hz, pulse 400 MUs, cycle 5
seconds on - 21 seconds off) or the MF (45 Hz, pulse 400 MUs, cycle 5 seconds on
12 seconds off) protocol. Peripheral microcirculation was monitored at the
thenar eminence using near-infrared spectroscopy (NIRS) to obtain tissue O2
saturation (StO2); a vascular occlusion test was applied before and after the
session. Local microcirculation of the vastus lateralis was also monitored using
NIRS. RESULTS: Thirty-one patients were randomized. In the HF protocol (17
patients), peripheral microcirculatory parameters were: thenar O2 consumption
rate (%/minute) from 8.6 +/- 2.2 to 9.9 +/- 5.1 (P = 0.08), endothelial
reactivity (%/second) from 2.7 +/- 1.4 to 3.2 +/- 1.9 (P = 0.04), vascular
reserve (seconds) from 160 +/- 55 to 145 +/- 49 (P = 0.03). In the MF protocol:
thenar O2 consumption rate (%/minute) from 8.8 +/- 3.8 to 9.9 +/- 3.6 (P = 0.07),
endothelial reactivity (%/second) from 2.5 +/- 1.4 to 3.1 +/- 1.7 (P = 0.03),
vascular reserve (seconds) from 163 +/- 37 to 144 +/- 33 (P = 0.001). Both
protocols showed a similar effect. In the vastus lateralis, average muscle O2
consumption rate was 61 +/- 9%/minute during the HF protocol versus 69 +/-
23%/minute during the MF protocol (P = 0.5). The minimum amplitude in StO2 was 5
+/- 4 units with the HF protocol versus 7 +/- 4 units with the MF protocol (P =
0.3). Post-exercise, StO2 increased by 6 +/- 7 units with the HF protocol versus
5 +/- 4 units with the MF protocol (P = 0.6). These changes correlated well with
contraction strength. CONCLUSIONS: A single NMES session affected local and
systemic skeletal muscle microcirculation. Medium and high frequency currents
were equally effective.
PMID- 24355423
TI - A multimodal Darwinian strategy for alleviating the atherosclerosis pandemic.
AB - The conflict between our 'primitive' genes and 'modern' lifestyle probably lies
at the root of several disorders that afflict modern man. Atherosclerosis, which
is relatively unknown among contemporary hunter-gatherer populations, has reached
pandemic proportions in recent times. Being an evolutionary problem with several
inter-related pathologies, current therapeutic strategy for treating
atherosclerosis has inherent limitations. Reviewing evolution-linked risk factors
suggests that there are four aspects to the etiology of atherosclerosis namely,
decreased intestinal parasitism, oversensitivity of evolutionarily redundant mast
cells, chronic underactivation of AMPK (cellular energy sensor) and a deficiency
of vitamin D. A combination of these four causes appear to have precipitated the
atherosclerosis pandemic in modern times. Man and worms co-existed symbiotically
in the past. Massive de-worming campaigns could have disrupted this symbiosis,
increasing nutritional availability to man (pro-obesity) at the cost of decreased
immunotolerance (pro-atherogenicity). A reduction in helminth-induced chronic TH2
activation could also have enhanced TH1 polarization, eventually disrupting the
reciprocal regulation of TH1/TH2 balance and resulting in atherosclerosis. The
riddance of helminth infestations may have rendered mast cells immunologically
redundant, making them oversensitive to inflammatory stimuli, thereby playing a
pro-atherogenic role. AMPK activation exerts pleiotropic anti-atherogenic
effects, such as suppression of fatty acid, cholesterol, protein synthesis,
reduction of vascular smooth muscle proliferation, etc. As energy deficit is the
chief stimulus for AMPK activation, the over-nourished modern man appears to be
suffering from chronic underactivation of AMPK, legitimising the unrivalled
supremacy of metformin, the oldest prescribed antidiabetic drug. The fact that
humans evolved in the sunny tropics suggests that humans are selected for high
vitamin D levels. Vitamin D deficiency is now linked to several conditions
including increased risk of CV disorders, diabetes, etc. The manifold decrease in
vitamin D levels in modern man justifies a need for supplementation. We therefore
hypothesize that a judicious combination of mast cell stabilization, AMPK
activation, vitamin D supplementation, and moderation in hygiene practices could
be an evolution-based multimodal strategy for both preventing and mitigating the
pandemic of atherosclerosis.
PMID- 24355424
TI - The search for a new paradigm to study micronutrient and phytochemical
bioavailability: from reductionism to holism.
AB - The study of micronutrient and phytochemical (MaP, i.e., non-energy nutrients)
bioavailability has been mainly studied through a reductionist and
pharmacological approach. This has led to associate one health effect to one MaP.
However, human interventional studies have given conflicting and disappointing
results about MaP supplementation. This is because the health effect is the
result of the synergetic action of numerous MaPs supplied by foods and/or diets
at nutritional doses. A food is not a drug. Therefore, there is a need for more
holistic approach to study MaP bioavailability, then their health effect to
achieve general recommendations. This paper aims to hypothesize for such a
paradigm shift in this topic and to lay new foundations for research in MaP
bioavailability.
PMID- 24355425
TI - Paramedics on the job: dynamic trunk motion assessment at the workplace.
AB - Many paramedics' work accidents are related to physical aspects of the job, and
the most affected body part is the low back. This study documents the trunk
motion exposure of paramedics on the job. Nine paramedics were observed over 12
shifts (120 h). Trunk postures were recorded with the computer-assisted CUELA
measurement system worn on the back like a knapsack. Average duration of an
emergency call was 23.5 min. Sagittal trunk flexion of >40 degrees and twisting
rotation of >24 degrees were observed in 21% and 17% of time-sampled postures.
Medical care on the scene (44% of total time) involved prolonged flexed and
twisted postures (~ 10s). The highest extreme sagittal trunk flexion (63 degrees
) and twisting rotation (40 degrees ) were observed during lifting activities,
which lasted 2% of the total time. Paramedics adopted trunk motions that may
significantly increase the risk of low back disorders during medical care and
patient-handling activities.
PMID- 24355426
TI - Diagnosis from functional perspectives: usefulness of a manual tactile test for
predicting precision pinch performance and disease severity in subjects with
carpal tunnel syndrome.
AB - OBJECTIVES: To investigate how the severity levels revealed in a nerve conduction
study (NCS) affect the results of the Manual Tactile Test (MTT) for patients with
carpal tunnel syndrome (CTS), and to examine the relationships between the
results of the MTT and precision pinch performance. DESIGN: Case-control studies.
SETTING: Hospital and local community. PARTICIPANTS: Patients with CTS (N=70)
with 119 affected hands were studied. A control group matched by age, sex, and
hand dominance was also recruited. INTERVENTION: Not applicable. MAIN OUTCOME
MEASURES: CTS severity was determined based on NCS findings. The MTT, traditional
sensory tests, and precision pinch performance were used to examine the
functional sensory status of the hand from different perspectives. RESULTS: The
patients with CTS exhibited deterioration in all of the sensibility tests
(P<.001). The results showed that the MTT could classify subgroups of severity in
CTS (P<.001). A moderate correlation was found between the results of the MTT and
precision pinch performance (r=.526-.585, P<.001). Multiple linear regression
analysis showed that the MTT results were useful indicators for predicting
precision pinch performance and differentiating severity in subjects with CTS
(r(2)=.376 and .323, respectively). CONCLUSIONS: The findings indicate that the
MTT could be a valid and useful assessment for hand sensibility and prehensile
pinch performance in patients with CTS.
PMID- 24355428
TI - Microbial fixation of CO2 in water bodies and in drylands to combat climate
change, soil loss and desertification.
AB - The growing concern for the increase of the global warming effects due to
anthropogenic activities raises the challenge of finding novel technological
approaches to stabilize CO2 emissions in the atmosphere and counteract impinging
interconnected issues such as desertification and loss of biodiversity.
Biological-CO2 mitigation, triggered through biological fixation, is considered a
promising and eco-sustainable method, mostly owing to its downstream benefits
that can be exploited. Microorganisms such as cyanobacteria, green algae and some
autotrophic bacteria could potentially fix CO2 more efficiently than higher
plants, due to their faster growth. Some examples of the potential of biological
CO2 mitigation are reported and discussed in this paper. In arid and semiarid
environments, soil carbon sequestration (CO2 fixation) by cyanobacteria and
biological soil crusts is considered an eco-friendly and natural process to
increase soil C content and a viable pathway to soil restoration after one
disturbance event. Another way for biological-CO2 mitigation intensively studied
in the last few years is related to the possibility to perform carbon dioxide
sequestration using microalgae, obtaining at the same time bioproducts of
industrial interest. Another possibility under study is the exploitation of
specific chemotrophic bacteria, such as Ralstonia eutropha (or picketii) and
related organisms, for CO2 fixation coupled with the production chemicals such as
polyhydroxyalkanoates (PHAs). In spite of the potential of these processes,
multiple factors still have to be optimized for maximum rate of CO2 fixation by
these microorganisms. The optimization of culture conditions, including the
optimal concentration of CO2 in the provided gas, the use of metabolic
engineering and of dual purpose systems for the treatment of wastewater and
production of biofuels and high value products within a biorefinery concept, the
design of photobioreactors in the case of phototrophs are some of the issues
that, among others, have to be addressed and tested for cost-effective CO2
sequestration.
PMID- 24355427
TI - Peripheral nerve function and lower extremity muscle power in older men.
AB - OBJECTIVE: To assess whether sensorimotor peripheral nerve function is associated
with muscle power in community-dwelling older men. DESIGN: Longitudinal cohort
study with 2.3+/-0.3 years of follow-up. SETTING: One clinical site.
PARTICIPANTS: Participants (n=372; mean age +/- SD, 77.2+/-5.1y; 99.5% white;
body mass index, 27.9+/-3.7kg/m(2); power, 1.88+/-0.6W/kg) at 1 site of the
Osteoporotic Fractures in Men Study (N=5994). INTERVENTIONS: Not applicable. MAIN
OUTCOME MEASURES: A nerve function ancillary study was performed 4.6+/-0.4 years
after baseline. Muscle power was measured using a power rig. Peroneal motor nerve
conduction amplitude, distal motor latency, and mean f-wave latency were
measured. Sensory nerve function was assessed using 10-g and 1.4-g monofilaments
and sural sensory nerve conduction amplitude and distal latency. Peripheral
neuropathy symptoms at the leg and feet were assessed by self-report. RESULTS:
After adjustments for age, height, and total body lean and fat mass, 1 SD lower
motor (beta=-.07, P<.05) and sensory amplitude (beta=-.09, P<.05) and 1.4-g
(beta=-.11, P<.05) and 10-g monofilament insensitivity (beta=-.17, P<.05) were
associated with lower muscle power/kg. Compared with the effect of age on muscle
power (beta per year, -.05; P<.001), this was equivalent to aging 1.4 years for
motor amplitude, 1.8 years for sensory amplitude, 2.2 years for 1.4-g
monofilament detection, and 3.4 years for 10-g detection. Baseline 1.4-g
monofilament detection predicted a greater decline in muscle power/kg. Short-term
change in nerve function was not associated with concurrent short-term change in
muscle power/kg. CONCLUSIONS: Worse sensory and motor nerve function were
associated with lower muscle power/kg and are likely important for impaired
muscle function in older men. Monofilament sensitivity was associated with a
greater decline in muscle power/kg, and screening may identify an early risk for
muscle function decline in late life, which has implications for disability.
PMID- 24355429
TI - Serum levels of irisin in gestational diabetes mellitus during pregnancy and
after delivery.
AB - OBJECTIVE: Irisin has recently been introduced as a novel an exercise-inducible
myokine which improves glucose metabolism in mice. However, regulation of
circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal
period has not been assessed so far. METHODS: Circulating irisin was quantified
in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls.
In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data
were also available. In a second study population of 40 healthy women with
singleton pregnancies undergoing elective Cesarean section, irisin was assessed
in maternal serum before and within 24h after delivery, as well as in umbilical
cord blood and in placental tissue. RESULTS: In the first study population,
median [interquartile range] irisin levels were significantly higher in GDM
patients as compared to controls after delivery (previous GDM: 446.3
[146.9]MUg/l; controls: 378.0 [111.4]MUg/l) but not during pregnancy (GDM: 482.1
[132.1]MUg/l; controls: 466.6 [178.0]MUg/l). Interestingly, fasting insulin (FI)
was independently and positively associated with serum irisin in multivariate
analysis during pregnancy. In agreement with these findings, relative changes
(ratio) of FI independently and positively predicted relative changes of irisin
(ratio) in the second study population. CONCLUSIONS: The myokine irisin is
independently associated with FI in pregnancy. The physiological significance of
these findings needs to be assessed in future experiments.
PMID- 24355430
TI - Neutrophil microparticles modulate cytokine production by natural killer cells.
AB - Neutrophil microparticles (NMs) are scarce in the circulation but are highly
enriched at sites of inflammation and exert profound effects on immune cells. In
the present study, we addressed whether NMs modulate cytokine-producing capacity
of natural killer (NK) cells. NMs inhibited the production of IFN-gamma and TNF
alpha but enhanced the release of TGF-beta1 by IL-2/IL-12-activated NK cells. The
inhibitory effect of NMs was strongly attenuated by blockade of
phosphatidylserine exposed on NMs. Thus, NMs skew the cytokine profile of NK
cells from pro-inflammatory toward anti-inflammatory, potentially favoring the
resolution of inflammation.
PMID- 24355431
TI - Screening for delirium in the emergency department: a systematic review.
AB - Older adults who visit emergency departments (EDs) often experience delirium, but
it is infrequently recognized. A systematic review was therefore conducted to
identify what delirium screening tools have been used in ED-based epidemiologic
studies of delirium, whether there is a validated set of screening instruments to
identify delirium among older adults in the ED or prehospital environments, and
an ideal schedule during an older adult's visit to perform a delirium evaluation.
MEDLINE/EMBASE, Cochrane, PsycINFO, and CINAHL databases were searched from
inception through February 2013 for original, English-language research articles
reporting on the assessment of older adults' mental status for delirium. Twenty
two articles met all study inclusion criteria. Overall, 7 screening instruments
were identified, though only 1 has undergone initial validation for use in the ED
environment and a second instrument is currently undergoing such validation.
Minimal information was identified to suggest the ideal scheduling of a delirium
assessment process to maximize the recognition of this condition in the ED. Study
results indicate that several delirium screening tools have been used in
investigations in the ED, though validation of these instruments for this
particular environment has been minimal to date. The ideal interval(s) during
which a delirium screening process should take place has yet to be determined.
Research will be needed both to validate delirium screening instruments to be
used for investigation and clinical care in the ED and to define the ideal timing
and form of the delirium assessment process for older adults.
PMID- 24355432
TI - Depression and reduced heart rate variability after cardiac surgery: the
mediating role of emotion regulation.
AB - BACKGROUND: Heart rate variability (HRV), as an index of autonomic nervous system
(ANS) functioning, is reduced by depression after cardiac surgery, but the
underlying mechanisms of this relationship are poorly understood. Poor emotion
regulation as a core symptom of depression has also been associated with altered
ANS functioning. The present study aimed to examine whether emotion dysregulation
could be a mediator of the depression-reduced HRV relationship observed after
cardiac surgery. METHODS: Self-reported emotion regulation and four-minute HRV
were measured in 25 depressed and 43 nondepressed patients after cardiac surgery.
Mediation analysis was conducted to evaluate emotion regulation as a mediator of
the depression-reduced HRV relationship. RESULTS: Compared to nondepressed
patients, those with depression showed lower standard deviation of normal-to
normal (NN) intervals (p<.05), root mean square successive difference of NN
intervals (p<.004), and number of interval differences of successive NN intervals
greater than 50ms (NN50) (p<.05). Increased low frequency (LF) in normalized
units (n.u.) and reduced high frequency (HF) n.u. were also found in depressed
compared to nondepressed patients (p's<.01). Mediation analysis revealed that
suppression of emotion-expressive behavior partially mediated the effect of
depression on LF n.u. and HF n.u. CONCLUSIONS: Results confirmed previous
findings showing that depression is associated with reduced HRV, especially a
reduced vagal tone and a sympathovagal imbalance, after cardiac surgery. This
study also provides preliminary evidence that increased trait levels of
suppression of emotion-expressive behavior may mediate the depression-related
sympathovagal imbalance after cardiac surgery.
PMID- 24355433
TI - Diversity and evolution of membrane intrinsic proteins.
AB - BACKGROUND: Membrane intrinsic proteins (MIPs) are the proteins in charge of
regulating water transport into cells. Because of this essential function, the
MIP family is ancient, widespread, and highly diverse. SCOPE OF REVIEW: The
rapidly accumulating genomic and transcriptomic data from previously poorly known
groups such as unicellular eukaryotes, fungi, green algae, mosses, and non
vertebrate animals are contributing to expand our view of MIP evolution
throughout the diversity of life. Here, by analyzing more than 1700 sequences, we
provide an updated and comprehensive phylogeny of MIPs MAJOR CONCLUSIONS: The
reconstructed phylogeny supports (i) deep orthology of X intrinsic proteins
(XIPs; present from unicellular eukaryotes to plants); (ii) that the origin of
small intrinsic proteins (SIPs) traces back to the common ancestor of all plants;
and (iii) the expansion of aquaglyceroporins (GLPs) in Oomycetes, as well as
their loss in vascular plants and in the ancestor of endopterygote insects.
Additionally, conserved positions in the protein, and residues involved in
glycerol selectivity are reviewed within a phylogenetic framework. Furthermore,
functional diversification of human and Arabidopsis paralogs are analyzed in an
evolutionary genomic context. GENERAL SIGNIFICANCE: Our results show that while
bacteria and archaea generally function with one copy of each a water channel
(aquaporin or AQP) and a GLP, recurrent independent expansions have greatly
diversified the structures and functions of the different members of both MIP
paralog subfamilies throughout eukaryote evolution (and not only in flowering
plants and vertebrates, as previously thought). This article is part of a Special
Issue entitled Aquaporins.
PMID- 24355435
TI - Reduced glutathione prevents camphorquinone-induced apoptosis in human oral
keratinocytes.
AB - OBJECTIVES: Camphorquinone (CQ) is a widely used photoinitiator in dental visible
light (VL)-cured resinous materials. However, little is known about the toxicity
of CQ in human cells. This study was designed to investigate CQ induced oxidative
strain and apoptosis in cultured human oral keratinocytes (OKF6/TERT 2).
Furthermore, the effects of visible-light (VL)-irradiation and the reducing agent
N,N-dimethyl-p-toluidine (DMT) were investigated. In addition, the preventive
potential of the antioxidant glutathione (GSH) against CQ induced toxicity was
analyzed as well. METHODS: The fluorescent DNA-staining dye Hoechst 33342 was
used to quantify total cell numbers. Intracellular levels of reactive oxygen
species (ROS) were measured by the fluorescent probe 2',7'-dichlorofluorescein
diacetate (DCFH-DA). Apoptosis was determined by FACS analysis (Annexin V
FITC/propidium iodide), by measuring caspase-3/7 activity (ELISA) and by DNA
laddering. RESULTS: Our data show that CQ was dose-dependent cytotoxic and caused
oxidative stress by inducing reactive oxygen species (ROS). The redistribution of
phosphatidylserine (PS) to the outer layer of the plasma membrane, induction of
caspase-3 enzyme activity and DNA fragmentation were also observed in CQ exposed
cells. Interestingly, CQ-induced ROS generation enhanced by VL irradiation or a
simultaneous treatment with DMT showed no quantitative effect on apoptosis.
However, co-exposure of cells with GSH significantly reduced the intracellular
ROS generation as well as apoptosis caused by CQ. SIGNIFICANCE: This is the first
report showing that ROS-induced apoptosis, which is caused by CQ, is prevented by
GSH.
PMID- 24355434
TI - Isoflurane modulates cardiac mitochondrial bioenergetics by selectively
attenuating respiratory complexes.
AB - Mitochondrial dysfunction contributes to cardiac ischemia-reperfusion (IR) injury
but volatile anesthetics (VA) may alter mitochondrial function to trigger
cardioprotection. We hypothesized that the VA isoflurane (ISO) mediates
cardioprotection in part by altering the function of several respiratory and
transport proteins involved in oxidative phosphorylation (OxPhos). To test this
we used fluorescence spectrophotometry to measure the effects of ISO (0, 0.5, 1,
2mM) on the time-course of interlinked mitochondrial bioenergetic variables
during states 2, 3 and 4 respiration in the presence of either complex I
substrate K(+)-pyruvate/malate (PM) or complex II substrate K(+)-succinate (SUC)
at physiological levels of extra-matrix free Ca(2+) (~200nM) and Na(+) (10mM). To
mimic ISO effects on mitochondrial functions and to clearly delineate the
possible ISO targets, the observed actions of ISO were interpreted by comparing
effects of ISO to those elicited by low concentrations of inhibitors that act at
each respiratory complex, e.g. rotenone (ROT) at complex I or antimycin A (AA) at
complex III. Our conclusions are based primarily on the similar responses of ISO
and titrated concentrations of ETC. inhibitors during state 3. We found that with
the substrate PM, ISO and ROT similarly decreased the magnitude of state 3 NADH
oxidation and increased the duration of state 3 NADH oxidation, DeltaPsim
depolarization, and respiration in a concentration-dependent manner, whereas with
substrate SUC, ISO and ROT decreased the duration of state 3 NADH oxidation,
DeltaPsim depolarization and respiration. Unlike AA, ISO reduced the magnitude of
state 3 NADH oxidation with PM or SUC as substrate. With substrate SUC, after
complete block of complex I with ROT, ISO and AA similarly increased the duration
of state 3 DeltaPsim depolarization and respiration. This study provides a
mechanistic understanding in how ISO alters mitochondrial function in a way that
may lead to cardioprotection.
PMID- 24355436
TI - Penetration and encapsulation of the larval endoparasitoid Exorista larvarum
(Diptera: Tachinidae) in the factitious host Galleria mellonella (Lepidoptera:
Pyralidae).
AB - The tachinid fly Exorista larvarum (L.) (Diptera: Tachinidae) is a polyphagous
larval endoparasitoid that deposits its eggs on the host exoskeleton of
lepidopteran and tenthredinid larvae. The attachment of larval E. larvarum and
the formation of the respiratory funnel were studied during infestation in the
last larval instar of the wax moth, Galleria mellonella (L.) (Lepidoptera:
Pyralidae). The tachinid larvae burrow through the host integument after
hatching, using their robust cephalopharyngeal skeleton, leaving a dark spot at
the point of their penetration as a result of host cuticle melanization.
Endoparasitoid penetration induces the host cellular defence, resulting in the
formation of a haemocyte capsule consisting of multi-cellular sheaths. This
enveloping capsule later undergoes melanization, which is mostly obvious towards
the posterior part of the endoparasitoid. The endoparasitoid uses the host
encapsulation response to build a respiratory funnel from the modified host
integument, leading to the host surface. The encapsulated larva remains attached
to the respiratory funnel via an anal hook and cuticular spines until fully
developed. Additional immunohistochemical analyses were used to study host
parasitoid interactions. Indirect immunofluorescence showed no labelling of
potential tachinid antigens and confirmed no effect on the surrounding host
tissues. A simulated parasitization with coated polybead microspheres revealed
the mortal impact of tachinid antigens to the host. Hosts injected with antigen
coated polybeads died as a consequence of an acute and extensive immunological
response to the tachinid antigens and not due to the trauma caused by foreign
objects inside their body.
PMID- 24355437
TI - Increased hepatic blood flow during enteral immune-enhancing diet gavage requires
intact enterohepatic bile cycling.
AB - OBJECTIVES: Total hepatic blood flow (HBF) via the hepatic artery and portal vein
is highly dependent on gastrointestinal perfusion. During postprandial hyperemia,
intestinal blood flow depends on nutrient composition, gastrointestinal location,
and time. Immune-enhancing diets (IEDs) containing n-3 polyunsaturated fatty
acids (PUFAs) selectively augment blood flow in the ileum at 60-120 min via a
bile-dependent mechanism. My colleagues and I hypothesized that liver blood flow
would be similarly affected by IEDs containing n-3 PUFAs. METHODS: Mean arterial
blood pressure, heart rate, and effective HBF (galactose clearance) were measured
in anesthetized male Sprague-Dawley rats after gastric gavage of either a control
diet (CD, Boost, Novartis) or an IED (Impact, Nestle Nutrition), with or without
bile-duct ligation (BDL), and with or without supplemental bile (bovine, dried,
unfractionated). Significance was assessed by 2-way ANOVA for repeated measures
with the Tukey-Kramer honestly significant difference test. RESULTS: Compared
with baseline levels, a CD increased HBF (peak at 40 min , *P < 0.05) whereas an
IED increased HBF in two distinct peaks at 40 min (*P < 0.05) and 120 min (*P <
0.05), but BDL prevented both the early (CD and IED, ?P < 0.05) and late peaks
(IED, ?P < 0.05). Bile supplementation in the CD + BDL or IED + BDL groups
restored neither the CD peak nor the early or late IED peaks. CONCLUSIONS: HBF
during absorptive intestinal hyperemia is modulated by a mechanism that requires
an intact enterohepatic circulation. The early peaks at 40 min (CD or IED) were
prevented by BDL, even though fat absorption in the proximal gut occurs by bile
independent direct absorption. Bile supplementation with the diet (CD + BDL or
IED + BDL) was insufficient to restore HBF hyperemia, which implies that a
relationship exists between intestinal and hepatic blood flow that is not solely
dependent on bile-mediated intestinal fat absorption and bile recirculation.
PMID- 24355438
TI - Long-lasting improved amino acid bioavailability associated with protein pulse
feeding in hospitalized elderly patients: a randomized controlled trial.
AB - OBJECTIVE: Aging is associated with a blunted anabolic response to dietary
intake, possibly related to a decrease in systemically available amino acids
(AAs), which in turn may stem from increased splanchnic AA metabolism. Splanchnic
sequestration can be saturated by pulse feeding (80% of daily protein intake in a
single meal), enabling increased protein synthesis. The aim of this study was to
explore whether protein pulse feeding increased postprandial AA concentrations,
and if so whether this increase persisted after 6 wk of dietary treatment.
METHODS: This prospective randomized study enrolled 66 elderly malnourished or at
risk patients in an inpatient rehabilitation unit. All were given a controlled
diet for 6 wk. In a spread diet (SD) group (n = 36), dietary protein was spread
over the four daily meals. In a pulse diet (PD) group (n = 30), 72% of dietary
protein (averaging 1.31 g/kg body weight daily) was consumed in one meal at noon.
The patients were evaluated on day 1 and at 6 wk for plasma postprandial (five
times from 0 to +180 min) AA concentrations (expressed as area under the curve
above baseline). RESULTS: Protein pulse feeding was more efficient than protein
spread feeding at increasing plasma postprandial AA concentrations, notably of
essential AAs. This increased postprandial AA bioavailability was maintained
after 6 wk. CONCLUSIONS: This study demonstrates that increased postprandial AA
bioavailability induced by protein pulse feeding persists after 6 wk (i.e., that
there is no metabolic adaptation blunting AA bioavailability).
PMID- 24355439
TI - Probiotic supplementation improves inflammatory status in patients with
rheumatoid arthritis.
AB - OBJECTIVES: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in
which the gut microbiota is altered. Probiotics are microorganisms that can
normalize gut microbiota; thus, they may help to alleviate RA symptoms. The
objective of the present clinical trial was to assess the effects of probiotic
supplementation on disease activity and inflammatory cytokines in patients with
RA. METHODS: Forty-six patients with RA were assigned into two groups in this
randomized, double-blind, placebo-controlled clinical trial. The patients in the
probiotic group received a daily capsule that contained a minimum of 10(8) colony
forming units of Lactobacillus casei 01 for 8 wk. The placebo group took capsules
filled with maltodextrin for the same time period. Questionnaires, anthropometric
measurements, and fasting blood samples were collected, and the participants were
assessed by a rheumatologist at baseline and at the end of the trial. RESULTS:
Disease activity score was significantly decreased by the intervention, and there
was a significant difference between the two groups at the end of the study (P <
0.01). Three of the assessed serum proinflammatory cytokines (tumor necrosis
factor-alpha, interleukin-6, and interleukin-12) significantly decreased in the
probiotic group (P < 0.05); however, serum levels of interleukin-1 beta were not
significantly affected by the probiotic (P = 0.22). The serum level of regulatory
cytokine (interleukin-10) was increased by the supplementation (P < 0.05). The
proportion of interleukin-10 to interleukin-12 was significantly increased in the
probiotic group as well. CONCLUSIONS: L. casei 01 supplementation improved the
disease activity and inflammatory status of patients with RA. Further studies are
warranted to confirm these results, and such confirmation may lead to the
introduction of probiotics as adjunctive therapy for this population.
PMID- 24355440
TI - Intratumoral distribution of EGFR-amplified and EGFR-mutated cells in pulmonary
adenocarcinoma.
AB - Alterations in the epidermal growth factor receptor (EGFR) gene are associated
with carcinogenesis in non-small cell lung cancer. However, the intratumoral
distribution of these abnormalities has not been elucidated. This study included
patients with surgically resected lung adenocarcinoma. The predominant
histological growth pattern was determined. Chromogenic in situ hybridization
(CISH) and EGFR-mutation specific-antibodies were used for analysis of changes in
gene copy number and EGFR mutations, respectively. EGFR mutation detected
immunohistochemistry (IHC) and amplification were identified in 31 (53%) and 30
(52%) cases, respectively. The predominant growth patterns in the 58 tumors
evaluated were papillary (28, 48%), lepidic (8, 14%), acinar (15, 26%), and solid
(7, 12%). EGFR mutations were the least common in cases with a solid predominant
pattern. The incidence of EGFR amplification did not differ among predominant
patterns. Analyzing each histological subtype, no differences were noted between
the prevalence of EGFR-IHC positive and CISH-positive rates. In the analysis of
EGFR amplification, CISH-positive status was more prevalent in IHC-positive cases
than in IHC-negative cases. All 19 cases that were both IHC and CISH positive
were analyzed. In 17 cases (90%), the IHC-positive area was equal to or larger
than the CISH-positive area. Among the histological subtypes of lung
adenocarcinoma, the solid predominant subtype was distinguishable by its
infrequent EGFR mutations. EGFR gene mutations preceded changes in oncogenic
drive, more so than did EGFR gene number alterations during the developmental
process of lung adenocarcinoma.
PMID- 24355441
TI - EBV associated lymphomas in 2008 WHO classification.
AB - Epstein-Barr virus (EBV) is a ubiquitous gamma-herpes virus that asymptomatically
infects more than 90% of the world's population. The exact mechanism of EBV in
oncogenesis is an area of active debate. However, EBV has been implicated in the
pathogenesis of several kinds of lymphomas and lymphoproliferative disorders,
including B-, T- and NK-cell derived. Subsequent studies have proven that the EBV
gene expression product plays an activating and/or promoting role on
lymphomagenesis, and paves the way for novel cellular therapies of EBV-associated
lymphomas. This review concentrates on the pathology, morphology, treatment and
prognosis of EBV-associated lymphomas in the 2008 WHO classification of tumors of
hematopoietic and lymphoma tissues.
PMID- 24355442
TI - Evaluation of five DNA extraction methods for detection of H. pylori in formalin
fixed paraffin-embedded (FFPE) liver tissue from patients with hepatocellular
carcinoma.
AB - Since Helicobacter spp. DNA was identified in liver tissue resected from patients
with hepatocelullar carcinoma (HCC), researchers have suggested a role of this
bacterium in hepatic carcinogenesis. Archives of formalin-fixed, paraffin
embedded (FFPE) tissues represent an extraordinary source for clinical studies
providing many advantages. However, DNA extraction from FFPE tissues is
laborious, time-consuming and still remains a challenge. The aim of this study
was to evaluate five protocols for DNA extraction from FFPE liver obtained from
patients with HCC in order to detect Helicobacter pylori DNA. These methods were:
(1) QIAamp FFPE Tissue Kit, (2) QIAamp DNA Mini Kit, (3) Wizard SV Genomic DNA
Purification System, (4) RealiaPrep FFPE gDNA Miniprep System and (5) phenol
chloroform. H. pylori detection was performed using 16S rRNA gene amplification
by PCR. The highest total amount of DNA was obtained using the phenol-chloroform
method. Analyses of 16S rRNA gene amplification did not show statistically
significant differences among the methods (p=0.466), although the highest
percentage of positive cases (70%) was found in samples extracted with phenol
chloroform. We suggest that of the five methods evaluated, phenol/chloroform is
the most suitable for detection of H. pylori in FFPE liver from patients with
HCC.
PMID- 24355443
TI - Occurrence and profiles of bisphenol analogues in municipal sewage sludge in
China.
AB - Extensive use of bisphenol A and its analogues has caused increasing concern over
the potential adverse health impacts of these chemicals. In this study, the
presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal
sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A
was the most frequently observed analogue (geometric mean: 20.5 ng/g dw).
Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84
ng/g dw) were found with similar frequency. Other BP analogues such as
tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were
identified for the first time in sewage sludge in China. Significant correlations
were found among BP concentrations, but no relationships were found with
wastewater treatment plant characteristics. Profiles of the relative estradiol
equivalents suggested that the estrogenic potential of BP mixtures may be
associated with the occurrence and contributions of specific analogues.
PMID- 24355444
TI - Corneal cross-linking for Acanthamoeba keratitis in an orthokeratology patient
after swimming in contaminated water.
AB - PURPOSE: To report a case of Acanthamoeba keratitis diagnosed using confocal
microscopy in a patient corrected by orthokeratology and treated with corneal
crosslinking (CXL) after failure to respond to medical treatment. METHODS: After
diagnosis, the patient was treated with several medications until CXL was applied
during one 30-min session using ultraviolet A radiation and application of
riboflavin. The clinical signs of the disease observed using slit-lamp
biomicroscopy and confocal microscopy were evaluated and the visual acuity was
measured during the course of the infection and treatment over a period of 30
months including 12 months of medical treatment, 9 months after cross-linking and
amniotic membrane transplant and 9 months after penetrating keratoplasty and
cataract extraction. RESULTS: In this case, confocal microscopy facilitated early
diagnosis of an Acanthamoeba infection even if other signs and symptoms might be
confounding. CXL was more effective than aggressive medication against the
microorganism. After CXL, the symptoms and the corneal appearance improved
significantly but the ulcer did not heal completely. After amniotic membrane
transplantation, the patient underwent penetrating keratoplasty (PK) with no
rejection, and the visual function substantially improved over 9 months of follow
up. CONCLUSIONS: Swimming in contaminated water might represent a risk for
orthokeratology patients. CXL was effective for treating Acanthamoeba keratitis
in an orthokeratology patient to eliminate active and cystic forms of the
microorganism. Confocal microscopy was useful to confirm the diagnosis in the
presence of confounding clinical signs observed during a conventional slit-lamp
examination. Both CXL and confocal microscopy are essential to the outcome of PK.
PMID- 24355445
TI - Differences in the pattern of anastomotic leakage after oesophagectomy in two
high-volume centres.
AB - INTRODUCTION: Complications to oesophageal and junctional cancer surgery are
common and have not diminished much during the past ten years. An unusually high
occurrence of anastomotic dehiscence occurred in Denmark in 2009 and 2010 as seen
in the national database for oesophagus, cardiac and gastric (ECV) cancer.
MATERIAL AND METHODS: In accordance with national guidelines, all patients
resected for oesophageal and junctional cancer in Denmark from 2003 were
prospectively entered into a national database. Data concerning anaesthesia, peri
and post-operative course, complications, re-operations and time spent in
intensive care unit were obtained retrospectively from hospital records. An in
depth analysis of data from two high-volume centres performing ECV cancer surgery
according to national guidelines was performed. RESULTS: A total of 881 patients
(Centre 1: 438; Centre 2: 443) were resected for oesophageal and junctional
cancer. A total of 79 patients with anastomotic insufficiency (AI) were detected
(Centre 1: 36; Centre 2: 43). By using a grading system, it was shown that AI was
more severe and occurred earlier in one centre than in the other. Possible
factors of influence are discussed, including neoadjuvant oncological therapy,
use of thoracoscopically performed anastomosis and perioperative inotrophic
drugs. CONCLUSION: Thanks to the establishment of a nationwide database in
pursuance of national guidelines, it was possible to detect variations in quality
of surgery over time, evaluate serious complications early and undertake an in
depth analysis of possible aetiological factors. Particularly, comparison was
facilitated by the use of a standardised grading system for complications.
FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
PMID- 24355446
TI - Early results after robot-assisted colorectal surgery.
AB - INTRODUCTION: Implementation of robotic technology in surgery is challenging in
many ways. The aim of this study was to present the implementation process and
results of the first two years of consecutive robot-assisted laparoscopic (RAL)
colorectal procedures. MATERIAL AND METHODS: The study was a retrospective study
of a consecutive, unselected patient population. All outcome parameters were
predefined and all patients completed 30-day follow-up. All parameters were
reported, including complication rate, reoperation rate and mortality. RESULTS:
From April 2010 to April 2012, a total of 223 elective RAL colorectal procedures
were performed. The procedures were grouped as follows: left colectomy/sigmoid
resection (n = 65), low anterior resection (n = 50), abdominoperineal resection
(n = 10), right colectomy (n = 56), rectopexia (n = 21), colectomy (n = 8),
palliative procedure (n = 8) and stoma reversal (n = 8). The overall mortality
rate was 0.4%; intra- and post-operative complication rates were 5.4% and 16%,
respectively; and the reoperation rate was 9%. Conversion to open surgery was
necessary in 9% of cases. A positive learning curve was found for low anterior
resections with a significant decrease in duration of surgery over the course of
the study period. CONCLUSION: RAL colorectal surgery can be performed as a
standard procedure for most colorectal procedures. Appropriate staff education,
surgical plan and quality assessment are necessary and we recommend a
credentialing system for robotic surgery certification. Future randomized
clinical trials should be performed to evaluate the short- and long-term results
in these patients. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
PMID- 24355447
TI - Reduced specialist time with direct computed tomography for suspected lung cancer
in primary care.
AB - INTRODUCTION: Lung cancer (LC) is the most common cause of cancer death in
Denmark, and triaging patients through fast-track diagnostic pathways is
recommended to improve patient outcome. Data on the most efficient triage
organisation of such pathways are limited. The aim of this study was to test a
strategy of a straight-to-test model for patients referred to the fast-track
pathway. Outcomes were number of computed tomographies (CT) performed, use of
specialist time and staff acceptability. MATERIAL AND METHODS: We performed a
randomised controlled study enrolling 493 patients who were referred from general
practice to fast-track LC evaluation (1 January-1 December 2012). Half of the
patients were randomly assigned to the intervention and went straight to a chest
CT before chest-physician evaluation. Time was measured for patients at random
days. Acceptability was examined in a focus group interview. RESULTS: In the
intervention group, 95.5% of patients had a CT performed compared with 97.2% in
the control group. There was no difference in the number of CTs between the
groups (risk difference (RD) = 1.3% (95% confidence interval (CI): 4.4-2.0; p =
0.454)). In the intervention group, chest-physician time was 13.3 min. (min.
max.: 7.7-19.5 min.) lower per referred patient than in the control group.
CONCLUSION: Giving general practitioners direct access to a CT did not change the
number of CTs performed and significantly reduced chest-physician time per
patient. In addition, the strategy was associated with high levels of staff
acceptability. FUNDING: The project was supported by the Danish Cancer Research
Foundation, the Danish Cancer Society and the Novo Nordisk Foundation. TRIAL
REGISTRATION: ClinicalTrials.gov: NCT01779726.
PMID- 24355448
TI - Patients with severe acquired brain injury show increased arousal in tilt-table
training.
AB - INTRODUCTION: Patients with severe acquired brain injury (ABI) are often
mobilised using a tilt-table. Complications such as orthostatic intolerance have
been reported. The primary objective of this study was to investigate if using a
tilt-table was feasible for mobilising patients with severe ABI admitted for sub
acute rehabilitation. We also investigated change in arousal, treatment duration
before termination due to orthostatic reactions and change in muscle tone.
MATERIAL AND METHODS: A total of 16 patients with severe ABI were included. The
patients were tilted head-up, and blood pressure, heart rate, breathing frequency
and eye opening were recorded before and during the intervention. Furthermore,
muscle tone was recorded before and after the intervention. RESULTS: Fifteen of
the 16 patients did not complete the 20-min. session of tilt training due to
orthostatic intolerance. There was a significant increase in the proportion of
time that the patients had open eyes during treatment as compared with before
treatment (p < 0.01). The mean time to occurrence of symptoms at the first,
second and third tilt was 244 (standard deviation (SD) = +/- 234) sec., 277 (SD =
+/- 257) sec. and 155 (SD = +/- 67) sec., respectively. CONCLUSION: Patients with
severe sub-acute ABI show orthostatic intolerance when mobilised on a tilt-table
which results in a low mobilisation intensity. However, the patients showed a
significant increase in arousal during mobilisation. FUNDING: No external funding
was received for this study. All resources were provided by the Department of
Neurorehabilitation, Traumatic Brain Injury Unit, Glostrup University Hospital.
TRIAL REGISTRATION: not relevant.
PMID- 24355449
TI - Difficulties in reaching therapeutic goals for hypertension and dysplipidaemia in
patients with type 2 diabetes in general practice.
AB - INTRODUCTION: National guidelines recommend strict control of blood pressure (BP)
and plasma low-density lipoprotein cholesterol (LDL) in type 2 diabetes (T2DM),
aiming at a BP <= 130/80 mmHg and an LDL concentration <= 2.5 mmol/l. Angiotensin
converting enzyme inhibitors (ACEI) or angiotensin II-receptor blockers (ARB) are
recommended as primary antihypertensive therapy (AHT). To which extent these
targets are met in Danish primary care is unknown. MATERIAL AND METHODS: This
study was based on data from 2,057 patients with T2DM who were randomly selected
from 64 general practitioners (GPs) from different regions of Denmark. Data were
collected from the GPs' electronic records. RESULTS: The mean age +/- standard
deviation was 66.2 +/- 11.6 years; 58.7% were male. The mean systolic BP +/-
standard deviation was 132.6 +/- 14.6 mmHg and the mean diastolic BP +/- standard
deviation was 78.1 +/- 9.0 mmHg. 47.7% of the patients met the BP target. 79.5%
of the patients were on AHT. 55.1% of the untreated and 46.0% of the treated
patients met the BP target. 83.4% of the treated patients received ACEI or ARB.
The median LDL was 2.2 (1.7-2.7) mmol/l. 63.7% of the patients met the LDL
target. 73.7% of the patients received lipid-lowering therapy. 32.8% of the
untreated and 74.4% of the treated patients met the LDL target. CONCLUSION: AHT
including ACEI and ARB and lipid-lowering therapy are widely used in T2DM in
Danish primary care, but only half of the patients are at target for BP and two
thirds are at target for LDL. Increased use of diuretics may improve BP control.
FUNDING: This study was funded by a grant from Boehringer Ingelheim, Denmark. The
grant covered costs related to data collection, time spent by the general
practitioners and data analysis by the DTU. TRIAL REGISTRATION: not relevant.
PMID- 24355450
TI - Effects of telemedicine in the treatment of patients with type 2 diabetes--a
study protocol.
AB - INTRODUCTION: Despite rehabilitation programmes offered to all patients with
newly diagnosed type 2 diabetes in Denmark, a number of patients either never
accomplish good diabetes regulation or the regulation deteriorates with time.
Therefore, new approaches are needed. The aim of the present study is to examine
whether telemedicine conferences with a nurse can contribute to achieving good
diabetes control among patients with poorly regulated type 2 diabetes. MATERIAL
AND METHODS: A total of 165 patients with type 2 diabetes who have formerly
undergone a rehabilitation programme are randomized to either telemedicine
intervention or usual care. The intervention lasts for 32 weeks and consists of
monthly videoconferences with a nurse from a health-care centre as an add-on to
usual care. Blood sugar, blood pressure and weight are regularly self-monitored
and measurements are automatically transferred to a database. Glycaemic control
(HbA1c level) is examined at baseline, 16 weeks, 32 weeks and 58 weeks (six
months post intervention). Blood pressure, weight, waist/hip ratio, quality of
life, physical activity, lipids, creatinine and haemoglobin are examined at
baseline and after 32 weeks. CONCLUSION: The study will examine whether
telemedicine technology can contribute to achieving good diabetes regulation.
FUNDING: The City of Copenhagen and the Prevention Fund of the Capital Region of
Denmark funded the project. Also "Smedemester Niels Hansen og Hustru Johanne F.
Frederiksens Legat" has supported the study. TRIAL REGISTRATION:
ClinicalTrials.gov registration number: NCT01688778.
PMID- 24355451
TI - Increased risk of complications in acute onset intestinal malrotation.
AB - INTRODUCTION: Intestinal malrotation is a potentially life-threatening illness
which presents in many different ways and the symptoms span from acute to
chronic. The purpose of this study was to determine the clinical presentation of
intestinal malrotation at all ages. MATERIAL AND METHODS: This was a
retrospective study of all patients operated for intestinal malrotation at Odense
University Hospital in the period from 1/1/1990 to 1/4/2012. The following
information was recorded in the hospital records: demographics, presentation,
duration of symptoms, diagnostic imaging and outcome. Patients were classified
into two age groups: children (0-15 years) and adults (over 15 years). RESULTS: A
total of 54 patients were identified - 47 children and seven adults. Children
frequently presented with acute symptoms, while adults mostly had chronic
symptoms. The mortality rate was 6% and 14% for children and adults, respectively
(p = 0.44). Deaths were due to volvulus. CONCLUSION: Intestinal malrotation may
have an acute and a chronic form in both children and adults. Complications and
death only occurred in patients with an acute onset. Proper knowledge about
symptoms is important for a good outcome. FUNDING: not relevant. TRIAL
REGISTRATION: not relevant.
PMID- 24355452
TI - Successful breast reconstruction using acellular dermal matrix can be recommended
in healthy non-smoking patients.
AB - INTRODUCTION: We present Scandinavia's first series of immediate alloplastic
breast reconstructions with an acellular dermal matrix. MATERIAL AND METHODS:
Data were collected retrospectively in 76 cases of immediate breast
reconstruction using an acellular dermal matrix (ADM) and an implant. RESULTS: A
total of 59 women were reconstructed between June 2011 and January 2013. Cases
included 42 unilateral and 17 bilateral reconstructions. A large number of
patients had adjuvant therapy, hormone therapy (34), radiation therapy (27) or
chemotherapy (38). The median age was 51 years (30-70 years) and the median
follow-up period was 326 days (68-624 days). The co-morbidity factors included
hypertension (n = 11), diabetes (n = 2) and 19 patients were smokers.
Unsuccessful reconstructions counted ten cases (13%), eight of these due to
necrosis and/or wound dehiscence (10%) and two due to infection (3%). The failure
rate in non-smokers was 2/52 (4%) compared with 8/24 (33%) in smokers, p = 0.001.
In hypertensive patients, the failure rate was 6/12 (50%) compared with 4/64
(6%)in normotensive patients, p = 0.001. 70% of the failed reconstructions
occurred in patients older than 65 years of age. CONCLUSION: Immediate
alloplastic breast reconstruction using an ADM can be recommended to healthy non
smoking patients. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
PMID- 24355453
TI - Only carefully selected patients may have a beneficial effect of salvage
cryoablation in recurrent prostate cancer after radiotherapy.
AB - INTRODUCTION: In Denmark, salvage cryoablation of locally recurrent prostate
cancer (sCAP) after curatively intended radiation therapy (RT) is the only
potentially curable option, and this experimental treatment has only been offered
at Aarhus University Hospital. This study presents our experiences with the
treatment. MATERIAL AND METHODS: sCAP procedures were performed from 2006 to
2012. Cases were registered prospectively. Recurrent disease was defined by the
Phoenix criterion (prostate-specific antigen (PSA) level > PSA nadir + 2 ng/ml).
RESULTS: A total of 39 sCAP treatments were performed in 37 patients. Four
patients had previously been treated with brachytherapy and 33 with external
radiation. There were two cases of hemiablations; the remaining cases were total
ablations. The median follow-up period was 42 (0-69) months and the age at the
time of treatment was 66 (53-78) years. Stratified according to D'Amico et al's
2003 risk definition, five patients had pre-RT intermediate-risk disease, and 31
had high-risk disease. Three cases could not be classified. Biochemical
recurrence was found in 27 cases, and the 12-month disease-free survival was
18.2% overall. No patient in the intermediate group had recurrence. In high-risk
patients, there were 25 cases of recurrence and the 12-month disease-free
survival was 10.7%. There were five (13%) cases of fistula formation and seven
(19%) cases of severe post-operative incontinence, all in previous high-risk
patients. Information on potency was deficient. CONCLUSION: In this limited
study, sCAP was very infrequently a curable treatment in high-risk patients, and
the treatment carried a high risk of severe morbidity. It seems, however, that
sCAP could be beneficial to patients, primarily in the intermediate-risk group.
FUNDING: The Central Denmark Region's Health Research Foundation and the Danish
Cancer Society financed the salary of the primary investigator. TRIAL
REGISTRATION: not relevant.
PMID- 24355454
TI - Radical prostatectomy for clinically localised prostate cancer at Rigshospitalet
1995-2011 - an analysis of surgical and oncological outcome.
AB - BACKGROUND: RP for localized PCa was introduced at Rigshospitalet in 1995. Since
then, the incidence of PCa and number of RPs performed every year has increased
enormously. Presently, RP is performed a six different hospitals in Denmark. No
previous studies have meticulously described outcomes of RP in Denmark. This PhD
thesis focuses on surgical and oncological outcome after RP at Rigshospitalet.
The primary purpose was to describe biochemical outcome, risk factors associated
with positive surgical margins, and the impact of margin location on risk of
biochemical recurrence. MATERIAL AND METHODS: The PhD-thesis is based on results
from approximately 1,300 men who underwent RP between 1995 and 2011 at
Rigshospitalet. The patients have been followed prospectively in a local
database. BR was defined as the first PSA >= 0.2 ng/ml and time to BR was
calculated from the date of surgery. Analysis of time to BR was done using Kaplan
Meier estimation and Cox regression analysis including both pre- and
postoperative parameters. The association between preoperative and surgical
parameters, including surgeon and nerve-sparing surgery, and PSM was analysed
using logistic regression analysis. RESULTS: The 10-year estimated BRFS was 75%,
60% and 39% for low-, intermediate-, and high-risk patients, respectively. An in
depth analysis of high-risk patients demonstrated a 10-year metastasis-free and
cancer-specific survival of 85% and 90%, respectively. A PSM was demonstrated to
increase the risk of BR up to 3 fold. The location of PSM was found to be
associated with the risk of BR, i.e. non-apical PSM had the highest risk of BR
compared to margin negative and apical PSM, especially in pT2 tumours. A number
of factors were found to correlate with the risk of PSM, especially preoperative
PSA, surgeon and nerve-sparing surgery. CONCLUSIONS: This thesis demonstrates
that outcome of RP at Rigshospitalet is comparable to international results. Our
studies confirm the prognostic importance of PSM, also in pT2 disease, and
indicate that location of PSM in pT2 may influence future selection of patients
for adjuvant treatment. Further, the selection of candidates for nerve-sparing
surgery seems to be associated with an increased risk of PSM and subsequent BR.
Therefore, the selection for nerve-sparing surgery remains unclear.
PMID- 24355455
TI - Diagnosis and treatment of haemorrhoids.
AB - These guidelines provide a review of diagnosis, conservative and surgical
treatment of haemorrhoids with primary focus on the surgical treatment. In
symptomatic hemorrhoids it is recommended, that conservative treatment is used as
basic treatment regardless of grading. The vast majority of grade II haemorrhoids
are treated conservatively, but surgery may be considered in a few cases with
pronounced symptoms. In these cases chirurgia minor, Doppler guided
dearterilization procedures or stapled haemorrhoidopexy are recommended. In grade
III and IV Doppler guided dearterilization procedures, stapled haemorrhoidopexy
(Grade III) or conventional Milligan Morgan haemorrhoidectomy are recommended.
PMID- 24355456
TI - Von Hippel-Lindau disease (vHL). National clinical guideline for diagnosis and
surveillance in Denmark. 3rd edition.
AB - These clinical guidelines outline the criteria and recommendations for diagnostic
and genetic work-up of families suspected of von Hippel-Lindau disease (vHL), as
well as recommendations for prophylactic surveillance for vHL patients. The
guideline has been composed by the Danish Coordination Group for vHL which is
comprised of Danish doctors and specialists interested in vHL. The
recommendations are based on longstanding clinical experience, Danish original
research, and extensive review of the international literature. vHL is a
hereditary multi-tumour disease caused by germline mutations in the VHL gene. vHL
is inherited in an autosomal dominant manner. Predisposed individuals are advised
to undergo prophylactic examinations, as they are at lifelong risk of developing
multiple cysts and tumours, especially in the cerebellum, the spinal cord, the
retina (hemangioblastomas), the kidneys (renal cell carcinoma), the adrenal
glands (pheochromocytoma), the pancreas, as well as in other organs. As many
different organs can be affected, several medical specialities often take part in
both diagnosis and treatment of manifestations. vHL should be suspected in
individuals with a family history of the disease, and/or in individuals with a
vHL-associated manifestation; i.e. a hemangioblastoma in the retina or the
central nervous system, familial or bilateral pheochromocytomas, familial,
multiple, or early onset renal cell carcinomas, and in individuals with an
endolymphatic sac tumour in the inner ear. Individuals suspected of vHL should be
referred to a department of clinical genetics for genetic work-up and counselling
as well as have a clinical work-up to identify any undiagnosed vHL-associated
manifestations. This guideline describes the elements of the clinical diagnostic
work-up, as well as the genetic work-up, counselling, and mutation screening.
Individuals who are affected with vHL, individuals at risk of vHL, and VHL
mutation carriers are advised to follow the surveillance program which consists
of regular prophylactic examinations relevant to different age groups. The
examinations are recommended to start in infancy with annual paediatric
examinations and ophthalmoscopy until the age of five years. From five to 14
years, annual plasma-metanephrine and plasma-normetanephrine tests, as well as
annual hearing examinations are added. Also, an MRI (Magnetic Resonance Imaging)
examination of the CNS and abdomen should be done between the ages of eight and
14 years. After the age of 15 years, individuals should be referred to: a) annual
ophthalmoscopy in dilation, b) annual neurological examination, c) every two
years: MRIs of the CNS, including the inner ear, d) annual ultrasound/MRI of the
abdomen, e) annual plasma-metanephrine, plasma-normetanephrine, and plasma
chromogranin A tests, and f) annual hearing examination at a department of
audiology. It is advised that one doctor takes on the responsibility of
coordination of and referral to the many examinations, and the communication with
the patient. To facilitate the coordination, and especially for the patients' own
use, a mobile chart can be used. In 2012, the Danish vHL Coordination Group
established a national vHL database comprising individuals with vHL and their
relatives, as well as individuals examined for vHL. The database is designated to
be a treatment and diagnostic instrument, as well as a tool in future vHL
research in Denmark.
PMID- 24355457
TI - Immune modulations during chemoimmunotherapy & novel vaccine strategies--in
metastatic melanoma and non small-cell lung cancer.
AB - This thesis describes the treatment of metastatic melanoma (MM) and non small
cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the
first part of the thesis was to assess how treatment with Temozolomide (TMZ)
chemotherapy affects the immune system in patients with metastatic MM. Our
results showed that the number of T lymphocytes was significantly reduced after 3
treatment cycles. Furthermore, the induced lymphopenia was positive correlated to
achievement of clinical benefit. We demonstrated that the proportion of CD4+ and
Treg lymphocytes decreased whereas the CD8+ T cells increased. In particular, we
demonstrated that mature CD8+ T cells increased during treatment. Analyses of
peripheral blood before and after treatment showed that T cell responses against
common viral epitopes were conserved despite chemotherapy. Surprisingly, we found
a significant increase in T cell responses against well-known MM tumour specific
antigens. Overall, we have verified that TMZ in addition to being an alkylating
and cytotoxic chemotherapy, also possess immune modulatory effect in MM patients
treated with standard dosage of TMZ. In the second part of the thesis we examined
how treatment with Interferon alfa-2b and Interleukin 2 (IFNalpha/IL2) affects
the immune system. We demonstrated a significant induced lymphocytosis during
treatment. Furthermore, we showed that the percentage increase in lymphocytes was
positively correlated to clinical outcome. Moreover, we have seen that
IFNalpha/IL2 leads to significant increase in NK and Treg cells in both patients
with and without clincal effect. In general, T cell responses against common
viral epitopes and well-known melanoma tumour specific antigens were low.
Furthermore, the study confirmed that elevated LDH is negatively correlated with
both treatment response and median overall survival. Overall, we have
characterized changes of immune cells and correlated them with clinical efficacy
during the couse of IFNalpha/IL2 used in standard dosage. In the third part we
investigated if vaccination with a peptide derived from IDO was feasible in
patients with metastatic NSCLC. This "First in Man" trial was safe and showed
modest side effects only. Since IDO was expressed in NSCLC tissues it was found
to be a relevant target. One patient achieved significant regression of liver
metastases (confirmed partial response) and another 6/15 patients achieved
prolonged disease stabilization. Furthermore, median overall survival was 25.9
months demonstrating a better survival in vaccinated compared to non-vaccinated
comparable NSCLC patients. The presence of IDO specific CD8+ T cells were
detected by IFNy Elispot. In patients with clinical effect of the vaccine IDO
specific CD8+ T cells at pre-treatment was significanctly increased. Moreover,
low-frequent IDO positive tetramer CD8+ T cells were detected and led to
effective killing of an IDO+ HLA-A2 positive cancer cell line (SW480) in 1
patient. Moreover, flow cytometry was performed and in general no significant
changes in CD8+ and CD4+ T cells were seen, although patients with clinical
response showed a trend towards increased mature CD8+ T cells during treatment.
In addition, we found lower levels of Tregs as well as an increased level of NK
cells after 6 vaccinations. Elevated Kyn/Trp ratio is suggested to mirror IDO
activity. In 8/11 patients the level after the 6th vaccine was stable compared to
baseline. No differences between patients with clinical benefit (4/5) and
patients with progressive disease (4/6) were demonstrated. Two patients had an
increase in Kyn/Trp ration meanwhile demonstrating a high expression of IDO. In 2
patients with clinical response long-term stabilization of Kyn/Trp was observed.
Overall, the vaccine was well tolerated with no adverse toxicity. Median overall
survival was 25.9 months with long term disease stabilization achieved in 47% of
the treated patients. Based on the promising clinical results achieved in the
vaccine trial for NSCLC patients, we launched a new clinical trial for MM
patients (ongoing patient recruitment) in June 2012. In order to enhance the
immune response the vaccine comprises IDO plus Survivin peptide as well as the
adjuvants Montanide, Aldara and GM-CSF. Finally, the vaccine is given in
combination with TMZ. Patients are evaluated every 3rd month with PET-CT scan.
Preliminary clinical data from the first 7/30 evaluable patients are presented.
Two patients demonstrated a patial response with 57% and 45% tumour regression
lasting for 10 months and 6+ months respectively, corresponding to a preliminary
objective response rate of 29%. The vaccine has been manageable and without
significant side effects.
PMID- 24355458
TI - Development of stable and reproducible biosensors based on electrochemical
impedance spectroscopy: three-electrode versus two-electrode setup.
AB - This work focuses on the development of electrochemical impedance biosensors
based on capacitance readout, for the detection of biomolecules in small sample
volumes. We performed electrochemical impedance spectroscopy (EIS) measurements
of DNA hybridization in electrochemical cells with microfabricated gold
electrodes. The time stability of the device was tested in two different
configurations: two microelectrodes in a microfluidic channel; two
microelectrodes plus a reference electrode in an electrochemical cell. Our
results demonstrate that the three-electrode setup is more stable, more
reproducible, and suitable for real-time measurements. In the last part of the
work we perform a test study of DNA hybridization in real time, and we show that
the three-electrode configuration can measure the process in situ and in real
time.
PMID- 24355459
TI - Ultra-sensitive electrical immunoassay biosensors using nanotextured zinc oxide
thin films on printed circuit board platforms.
AB - This study demonstrates the development of nanotextured zinc oxide (ZnO) thin
films sputter deposited on printed circuit boards (PCB) to enhance the capability
in detecting low concentrations of the protein troponin-T. The presence of this
particular biomarker in the bloodstream is a direct indicator of current and/or
future risk of various forms of cardiovascular diseases. Electrical transduction
through impedance spectroscopy was used to detect troponin-T functionalized
immunoassays on nanotextured ZnO surfaces. Calibration of the immunoassay was
performed by measuring the impedance changes resulting from the binding of
increasing concentrations of troponin-T to the immobilized antibodies on the ZnO
surface in (i) phosphate buffered saline (PBS) and (ii) human serum. The limit of
detection achieved using this platform was 10 fg/mL and 100 fg/mL in PBS and
human serum, respectively. Enhanced detection of troponin-T was found to
correlate to the oxygen vacancies in the ZnO thin film. PCB was chosen as the
substrate for ease of integration with microelectronic device manufacturing.
PMID- 24355460
TI - A simple biofuel cell cathode with human red blood cells as electrocatalysts for
oxygen reduction reaction.
AB - A red blood cell (RBC) from human exhibited direct electron transfer (DET)
activity on a bare indium tin oxide (ITO) electrode. A formal potential of -0.152
V vs. a silver-silver chloride saturated potassium chloride (Ag|AgCl|KCl(satd.))
was estimated for the human RBC (type AB) from a pair of redox peaks at around
0.089 and -0.215 V (vs. Ag|AgCl|KCl(satd.)) on cyclic voltammetric (CV)
measurements in a phosphate buffered saline (PBS; 39 mM; pH 7.4) solution. The
results agreed well with those of a redox couple for iron-bearing heme groups in
hemoglobin molecules (HbFe(II)/HbFe(III)) on the bare ITO electrodes, indicated
that DET active species were hemoglobin (Hb) molecules encapsulated by a
phospholipid bilayer membrane of the human RBC. The quantity of electrochemically
active Hb in the human RBC was estimated to be 30 pmol cm(-2). In addition, the
human RBC exhibited oxygen reduction reaction (ORR) activity in the dioxygen (O2)
saturated PBS solution at the negative potential from ca. -0.15 V (vs.
Ag|AgCl|KCl(satd.)). A single cell test proved that a biofuel cell (BFC) with an
O2|RBC|ITO cathode showed the open-circuit voltage (OCV) of ca. 0.43 V and the
maximum power density of ca. 0.68 MUW cm(-2).
PMID- 24355461
TI - Highly sensitive and selective optofluidics-based immunosensor for rapid
assessment of Bisphenol A leaching risk.
AB - Bisphenol A (BPA), a xenoestrogenic endocrine-disrupting chemical, is used in
many consumer products worldwide and is widely detected in the environment and in
food. Combining the advantages of evanescent wave fiber optic sensor and
microfluidic technology, an all-fiber optofluidics-based bioassay platform (AFOB)
was developed for the rapid immunoassay and assessment of BPA. The captured
molecular BPA-bovine serum albumin was covalently immobilized on the surface of
the fiber optic sensor. A mixture of different concentrations of BPA and a
certain concentration of fluorescence-labeled anti-BPA monoclonal antibodies
after pre-reaction was introduced to the optofluidic cell. A higher concentration
of BPA reduced the fluorescence-labeled antibodies bound to the sensor surface
and thus reduced fluorescence signals. Under optimal conditions, the BPA
quantified as 0.5-100 MUg/L, with a detection limit of 0.06 MUg/L. The high
selectivity of the sensor was evaluated in terms of its response to several
potentially interfering chemicals. The potential interference of an environmental
sample matrix was assessed by spiked samples, and the recovery of BPA ranged from
90% to 120% with relative standard deviation values of <9.1%. The AFOB and high
performance liquid chromatography had a desired correlation (R(2)=0.9958). The
sensing platform was successfully used to assess BPA leaching from polycarbonate
bottles at 45 degrees C and 80 degrees C, indicating that more BPA was
substantially leached at elevated temperature and extend time. Thus, the
developed sensing strategy can be an alternative method to rapidly analyze and
assess the migration mechanism and fate of BPA or other pollutants.
PMID- 24355462
TI - Coiled-coil peptide based sensor for ultra-sensitive thrombin detection.
AB - Comb structured gold microelectrode array (CSGMA) functionalized with self
assembled monolayer of thiol terminated coiled-coil peptide (CCP) linked together
by the thrombin specific cleavage site (Leu-Val-Pro-Arg-Gly-Ser) has been used to
fabricate an ultrasensitive, disposable, electrochemical thrombin biosensor. CCP
with thiol at one end provides the ease of CSGMA functionalization and the
presence of thrombin specific peptide in the middle of coiled-coil peptide
provides site for thrombin capture and detection. CCP/CSGMA electrodes were
characterized using label-free electrochemical impedance (EIS) technique and
exposed to solutions with different thrombin concentrations for its estimation.
Results reveal that CCP/CSGMA electrodes have a limit of detection (LOD) of 10
fg/ml (28 fM) and are able to detect catalytic activity of thrombin within 30 min
time frame. CCP/CSGMA electrodes were found to be selective against other IgG
anti-bodies such as DO1 and HA. Thus, CCP/CSGMA electrodes provide high
specificity toward thrombin detection and mechanistic details of binding and
cleavage process.
PMID- 24355463
TI - Improved activity of immobilized antibody by paratope orientation controller:
probing paratope orientation by electrochemical strategy and surface plasmon
resonance spectroscopy.
AB - Electrochemical method and surface plasmon resonance (SPR) spectroscopic analysis
are utilized herein to investigate antibody immobilization without and with
orientation control for site-positioning paratopes (antigen binding site) of the
antibody molecules. Biotin and its antibody were selected in current study as
model. Such an approach employed thiophene-3-boronic acid (T3BA) as paratope
orientation controller, (i) enabled site orientation of the antibody molecules
reducing the hiding of paratopes, and (ii) maintained the activity of the
captured antibodies, as confirmed by electrochemical and SPR analysis. Anti
biotin antibody (a glycoprotein) was covalently bound to a self-assembled
monolayer of T3BA modified on a nanogold-electrodeposited screen-printed
electrode through boronic acid-saccharide interactions, with the boronic acid
units specifically binding to the glycosylation sites of the antibody molecules.
The immunosensor functioned based on competition between the analyte biotin and
biotin-tagged, potassium hexacyanoferrate(II)-encapsulated liposomes. The current
signal produced by the released liposomal Fe(CN)6(4-), measured using square wave
voltammetry, yielded a sigmoidally shaped dose-response curve that was linear
over eight orders of magnitude (from 10(-11) to 10(-3)M). Furthermore this
biosensing system fabricated based on T3BA approach was found to possess
significantly improved sensitivity, and the limit of detection toward biotin was
calculated as 0.102 ng mL(-1) (equivalent to 6 MUL of 4.19 * 10(-10)M biotin).
PMID- 24355464
TI - Neighbourhood amenities and health: examining the significance of a local park.
AB - This paper reports the results of a qualitative study that examines the links
between neighbourhood spaces and quality of life for nine formerly homeless women
who live in a supportive housing development in Ottawa, Ontario. It explores a
local park that participants subjectively identified as the most meaningful place
influencing their health and quality of life. Looking at the neighbourhood from
the participants' perspectives, this paper discusses the links between access to
nearby urban green space, feelings of well-being, and having a sense of belonging
to the broader community. The primary methods used in our study were photovoice,
whereby participants were asked to take pictures of both healthy and unhealthy
aspects of their neighbourhood, and participant observation of the women's
interactions with their immediate and neighbourhood living environments. The
participants used photographs as a tool to help describe their experiences of the
park as not only a therapeutic or health-promoting place, but also an un
therapeutic or health-denying place. Participant observation helped fill the gaps
that women were unable to articulate in the interviews. The results reveal that
participants placed more emphasis on inclusive (free of charge) social events and
the ability to interact with others at the park than on its aesthetics. This
finding supports the notion that while beautification certainly has value,
resources to support free community events in public spaces are at least equally
important for establishing feelings of inclusion in the community among
marginalized populations.
PMID- 24355465
TI - Political, cultural and economic foundations of primary care in Europe.
AB - This article explores various contributing factors to explain differences in the
strength of the primary care (PC) structure and services delivery across Europe.
Data on the strength of primary care in 31 European countries in 2009/10 were
used. The results showed that the national political agenda, economy, prevailing
values, and type of healthcare system are all important factors that influence
the development of strong PC. Wealthier countries are associated with a weaker PC
structure and lower PC accessibility, while Eastern European countries seemed to
have used their growth in national income to strengthen the accessibility and
continuity of PC. Countries governed by left-wing governments are associated with
a stronger PC structure, accessibility and coordination of PC. Countries with a
social-security based system are associated with a lower accessibility and
continuity of PC; the opposite is true for transitional systems. Cultural values
seemed to affect all aspects of PC. It can be concluded that strengthening PC
means mobilising multiple leverage points, policy options, and political will in
line with prevailing values in a country.
PMID- 24355466
TI - Perceptions of susceptibility to pregnancy among U.S. women obtaining abortions.
AB - More than half (52%) of unintended pregnancies in the United States (U.S.) occur
among the 10.7% of women using no contraceptive method. We interviewed a sample
of women obtaining abortions in the U.S. in 2008 (n = 49) and explored their
attitudes toward and beliefs about their risk of pregnancy. We found that most
respondents perceived themselves to have a low likelihood of becoming pregnant at
the time that the index pregnancy occurred. Respondents' reasons for this
perceived low likelihood fell into four categories: perceived invulnerability to
pregnancy without contraceptive use, perceptions of subfecundity, self-described
inattention to the possibility of conception and perceived protection from their
current use of contraception (although the majority in this subgroup were using
contraception inconsistently or incorrectly). About half of the women discussed
more than one reason when explaining why they perceived themselves to have a low
risk of pregnancy at that time. We propose a modified Health Belief Model to
account for women's low perceived susceptibility to pregnancy based on our
results. Further research is needed to quantify the proportion of women who are
at risk of pregnancy who do not believe they are at risk and their reasons why,
so as to be able to better address women's misconceptions about fecundity and
conception with the goal of preventing unintended pregnancy.
PMID- 24355467
TI - Subjective well-being and the measurement of quality in healthcare.
AB - Quality continues to be placed at the heart of discussions about healthcare. This
raises important questions about precisely what quality care is, and how it
should be measured. An overall measure of subjective well-being (SWB) that
assesses and joins up different stages of the treatment process, and the
different people affected, could potentially be used to capture the full impact
of quality care throughout the entire treatment process. This article presents a
temporal model through which SWB links all stages in the treatment and care
process, thus allowing the overall quality of care to be determined and valued
according to its direct effect on people's lives. Drawing on existing medical and
behavioural studies, we populate this model with evidence that demonstrates how
SWB is affected at different points along the patient pathway. SWB is shown to
have an effect on outcomes at all stages of the treatment experience and improved
health and quality outcomes are shown to consistently enhance SWB. Furthermore,
SWB measures are shown to be a suitable method to value the impact of healthcare
on the families and carers of patients and, in this way, can join up health
outcomes to show wider effects of treatment on patients' lives. Measuring an
individual's SWB throughout his or her treatment experience can enable a full
appraisal of the quality of care that they receive. This will facilitate service
improvements at the micro level and help value treatments for resource allocation
purposes at the macro level.
PMID- 24355469
TI - Prospective study on the reciprocal relationship between intimate partner
violence and depression among women in Korea.
AB - This study aimed to examine the bi-directional relationship between intimate
partner violence (IPV) and depression using prospective data. Data from the
Korean Welfare Panel Study (KOWEPS) were used to test whether IPV was associated
with an increased overall level of depression and with the rate of change over
time in depressive symptoms and whether this model of change in depressive
symptoms was associated with subsequent incidences of IPV. This study utilized
data from 3153 married women who participated in the KOWEPS from 2006 through
2009. The KOWEPS is a panel study of a nationally representative sample of Korean
households. The women's responses to multiple questions adopted from the Conflict
Tactics Scale (CTS) were used to create a dichotomous IPV variable at Wave1 and
Wave4. The CESD-11 was used to measure the women's level of depression. We
utilized a latent growth model (LGM) of depression using IPV at Wave1 as a
predictor and IPV at Wave4 as an outcome predicted by the model parameters of the
LGM of depression. We found that after controlling for the effects of age,
education, social support and income, IPV at Wave1 was positively associated with
overall depression levels and negatively associated with the growth rate of
depression. Further, IPV at Wave4 was associated with the intercept and the slope
of the depression LGM and with IPV at Wave1. The overall model fit the data well.
This study indicated that experiencing IPV influences a woman's level of
depression in terms of its overall level and rate of change, which, in turn,
influences the victim's likelihood of experiencing subsequent IPV.
PMID- 24355468
TI - Stakeholder perceptions of thoracic rapid tissue donation: An exploratory study.
AB - Rapid autopsy or rapid tissue donation (RTD) is a novel method of tissue
procurement in which 'fresh' tissue is collected within 2-6 h following the death
of a patient. While the use of RTD offers many opportunities to develop new
therapies for lung cancer patients, it raises ethical concerns. The purpose of
this study was to examine knowledge, perceptions and ethical concerns about
recruiting patients for an RTD program. To achieve research goals, we conducted
six focus groups, each containing 5-10 participants (N = 38). Participants were
cancer patients (n = 17) their caregivers (n = 6), physicians (n = 6) and clinic
staff (n = 9) from the Thoracic Oncology Program at Moffitt Cancer Center, in
Tampa, Florida, USA. All focus groups were audio-recorded and conducted using a
semi-structured focus group guide. The transcripts were analyzed using hand
coding methods. Data were coded independently by at least two researchers, and an
inter-rater reliability rate of >=90% was achieved. Knowledge about RTD was low
among all groups, with physicians having slightly higher knowledge; all groups
agreed that RTD offered major benefits to cancer research; physicians and clinic
staff were mainly concerned about making a patient feel uncomfortable and
reducing hope, while, patients and family members were more concerned about
logistics and how the family would be affected during tissue retrieval. All
groups agreed the physician was the appropriate person to begin a discussion
about RTD and that recruitment should be individualized. All groups reported that
physician training is necessary, as well as an awareness campaign for patients
and families to be more receptive about RTD. The results of this study suggested
more education is needed for all stakeholders to learn about RTD prior to the
initiation of a research program. Our approach of querying all stakeholders
provides a firm foundation for future training modules regarding RTD programs in
lung cancer.
PMID- 24355470
TI - "I was pretty sure I had the 'flu": qualitative description of confirmed
influenza symptoms.
AB - Influenza is a common infectious disease, yet its diagnosis is rarely confirmed,
rather is presumed in the presence of non-specific clinical symptoms. Public
health organisations enlist the lay person in the diagnostic process, as
infection containment initiatives focus on encouraging individuals with influenza
like illness to stay at home, seeking medical attention only in the presence of
complications. While lay self-diagnosis of influenza has been confirmed to be
neither specific nor sensitive, little is known about how people with confirmed
influenza infection describe their illness. In this article we report the
descriptions of influenza by 21 individuals with rapid antigen test-kit
confirmation of influenza A or B and we discuss their recommendations for
management of future influenza infection. Semi-structured interviews reveal that
the variability in symptoms and severity of disease makes a standard description
of influenza elusive. Almost all participants had a cough, sweats, runny nose and
muscle aches, but the prominence of these symptoms varied significantly between
participants. Most participants were preoccupied with diagnostic certainty, and
would seek medical attention in a future similar illness episode. This study
underlined a conditioned recourse to medical authority for confirmation of
diagnosis which challenges current public health strategies and should be further
explored in order to determine its wider impact.
PMID- 24355472
TI - Making families: organizational boundary work in US egg and sperm donation.
AB - Egg and sperm donation can create distinct issues for designating family
boundaries. These issues come to the forefront as relations between donors,
recipients, and donor-conceived children have been shifting from anonymous to
more open arrangements in the US and other western countries. In this study, I
address US organizational practices and family boundary construction. Fertility
clinics, egg donation agencies, and sperm banks are central providers of US
gamete donation services. Given the disruptive potential of gamete donation, how
do they manage relationships between parties? Through a content analysis of
materials from twenty fertility clinics, twenty egg donation agencies, and thirty
one sperm banks, I address three major strategies of organizational boundary
work: 1) creating identity categories, 2) managing information, and 3) managing
interaction. I ultimately argue that even as many organizations offer
opportunities for connections between parties, they exercise social control over
donation arrangements through bounded relationships.
PMID- 24355471
TI - Neighborhood Hispanic composition and depressive symptoms among Mexican-descent
residents of Texas City, Texas.
AB - Substantial research shows that increased Hispanic neighborhood concentration is
associated with several beneficial health outcomes including lower adult
mortality, better self-rated health, and fewer respiratory problems. Literature
on the relationship of Hispanic composition and depressive symptoms is more
equivocal. In addition, few studies have directly investigated hypothesized
mechanisms of this relationship. This study uses data from a probability sample
of 1238 Mexican-descent adults living in 48 neighborhoods in Texas City, Texas.
Multilevel regression models investigate whether Hispanic neighborhood
composition is associated with fewer depressive symptoms. This study also
investigates whether social support, perceived discrimination, and perceived
stress mediate or moderate the relationship, and whether results differ by
primary language used at home. We find that individuals living in high Hispanic
composition neighborhoods experience fewer depressive symptoms than individuals
in low Hispanic composition neighborhoods. In addition, we find that these
beneficial effects only apply to respondents who speak English. Social support,
perceived discrimination, and perceived stress mediate the Hispanic composition
depressive symptoms relationship. In addition, discrimination and stress moderate
the relationship between Hispanic composition and depressive symptoms. Our
findings support theories linking higher neighborhood Hispanic composition and
better mental health, and suggest that Spanish language use, social support,
discrimination and stress may play important roles in the Hispanic composition
depressive symptoms relationship.
PMID- 24355473
TI - A matter of perception: exploring the role of income satisfaction in the income
mortality relationship in German survey data 1995-2010.
AB - Individual- and community-level income has been shown to be linked to social
inequalities in health and mortality. On the individual level, social comparisons
and relative deprivation resulting from them have been identified as relevant
mechanisms involved in the relationship between income and health, but it is
mainly income-based measures of relative deprivation that have been considered in
previous studies. Using income satisfaction, this study employs a perception
based indicator of relative deprivation. The study, covering the period between
1995 and 2010, utilized the German Socio-Economic Panel. The follow-up included
11,056 men and 11,512 women at employment age 25-64. Discrete-time survival
analysis with Cox regression was performed to estimate the effects of relative
income position and income satisfaction on all-cause mortality. The univariate
analysis revealed an income gradient on mortality and further showed a strong
association between income satisfaction and survival. After education and
employment status were adjusted for, the effect of discontent with income on
mortality was still present in the female sample, whereas in the male sample only
the income gradient prevailed. When self-rated health was controlled for, the
hazard ratios of income satisfaction attenuated and turned non-significant for
both men and women while the effects of income position remained stable. In
conclusion, the findings suggest that income satisfaction and income position
measure different aspects of income inequality and complement one another. Income
satisfaction appeared to be a possible contributing component to the causal
pathway between income and mortality.
PMID- 24355474
TI - Between surveillance and subjectification: professionals and the governance of
quality and patient safety in English hospitals.
AB - Two understandings of the dynamics of power developed by Foucault have been
extensively used in analyses of contemporary healthcare: disciplinary power and
governmentality. They are sometimes considered alternative or even contradictory
conceptual frameworks. Here, we seek to deploy them as complementary ways of
making sense of the complexities of healthcare organisation today. We focus on
efforts to improve quality and safety in three UK hospitals. We find a prominent
role for disciplinary power, including a panoptic gaze that is to some extent
internalised by professionals. We suggest, however, that the role of disciplinary
power relies for its impact on complementary strategies that are more akin to
governmentality. These strategies foster organisational contexts that are
receptive to disciplinary work. More fundamentally, we find that both
disciplinary power and governmentality work on subjectivities in rather a
different manner from that suggested by conventional accounts. We offer an
alternative, less individualised and more socialised, understanding of the way in
which power acts upon subjectivity and behaviour in professional contexts.
PMID- 24355476
TI - Dealing with moral dilemma raised by adaptive preferences in health technology
assessment: the example of growth hormones and bilateral cochlear implants.
AB - The aim of this article is to assess dilemma raised by adaptive preferences in
the economic evaluation of growth hormone (GH) treatment for non-GH-deficient
short children, and of bilateral cochlear implants for deaf children. Early
implementation of both technologies and their irreversible consequences increase
the potential conflicts faced by the assessors of health-related quality of life
(HRQoL) states (on behalf of patients) who could be interviewed (parents,
individuals with an experience of the same disability, or representative samples
of the general public). Indeed, assessors' preferences may be influenced by their
own situation and they are likely to vary according to age and the experience of
disability. Three options are put forward which aim to resolve these moral
dilemma and help economists make methodological choices that cannot be avoided in
order to carry out this assessment. They are grounded on three specific
egalitarian theories of social justice. The main contribution of this article is
to show that a dialogue between ethics and economics, prior to an assessment,
makes it possible to redefine the choice of effectiveness criteria (subjective
well-being, capabilities or social outcomes), the choice of perspective (patients
or the able-bodied), as well as the scope of assessment (medical and non-medical
care).
PMID- 24355475
TI - "I'm thrilled that you see that": guiding parents to see success in interactions
with children with deafness and autistic spectrum disorder.
AB - Children with deafness who are also on the autistic spectrum are a group with
complex support needs. Carers worry about their ability to communicate with them,
and are often uncertain about what constitutes 'good' communication in this
context. This paper analyses the use of a therapeutic intervention, Video
Interaction Guidance (VIG), which originates in developmental psychology and
focuses on the relational foundations of communication. We draw on a single case
using an ethnomethodological/conversation analytic framework, and in particular
Goodwin's (1994) work on 'professional vision', to show how the ability to see
'success' is a socially situated activity. Since what counts as success in this
setting is often far removed from everyday ideas of good communication, how
guiders facilitate particular 'ways of seeing' are critical for both the support
of carers and the impact of the intervention. We argue that this work has
implications in three areas: for the practice of VIG itself; for the role of
qualitative, interactional research addressing the way in which interaction-based
interventions are protocolised, enacted and assessed; and for the way in which
expertise is conceptualised in professional/client interactions in health and
social care.
PMID- 24355477
TI - Online and in-person health-seeking for infertility.
AB - Using data from Wave 1 (2004-2006) of the National Survey of Fertility Barriers
(NSFB), a national probability sample of women ages 25-45, we examine online
information-seeking among ever-infertile women. Of the 1352 women who met
criteria for infertility, 459 (34%) neither talked to a doctor nor went online
for information, 9% went online only for information, 32% talked to a doctor but
did not go online, and 25% did both. Guided by Chrisman's Health-Seeking Model
and previous research on Internet use to obtain health information, we employ
multinomial logistic regression to compare these four groups of ever-infertile
women. Findings generally support Chrisman's model. Infertile women tend to seek
information online as a complement to, rather than as a substitute for, in-person
health-seeking. Greater faith in the ability of medical science to treat
infertility and greater perceived stigma were associated with higher odds of
using the Internet to obtain information about infertility. In general, women who
perceived the symptoms of infertility as more salient had higher odds of using
both online and in-person or only in-person health-seeking compared to online
health-seeking. Women with greater resources had higher odds of using online
sources of information. Strong network encouragement to seek treatment was
associated with higher odds of in-person health-seeking and combining in-person
and online health-seeking compared to only going online or doing nothing.
PMID- 24355478
TI - Entangled ethnography: imagining a future for young adults with learning
disabilities.
AB - Our article draws on one aspect of our multi-sited long-term ethnographic
research in New York City on cultural innovation and Learning Disabilities (LD).
We focus on our efforts to help create two innovative transition programs that
also became sites for our study when we discovered that young adults with
disabilities were too often "transitioning to nowhere" as they left high school.
Because of our stakes in this process as parents of children with learning
disabilities as well as anthropologists, we have come to think of our method as
entangled ethnography, bringing the insights of both insider and outsider
perspectives into productive dialog, tailoring a longstanding approach in
critical anthropology to research demedicalizing the experience of disability.
PMID- 24355479
TI - Frequency and genetic spectrum of maturity-onset diabetes of the young (MODY) in
southern New Zealand.
AB - Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes,
consisting of a heterogeneous group of autosomal dominant inherited disorders.
Typical onset is in individuals prior to twenty five years, and presentation can
mimic type 1 or 2 diabetes. Molecular genetic testing can allow precise
identification of the different MODY sub-types. Making a specific diagnosis of
MODY can have important implications for the guidance of appropriate treatment,
prognosis and genetic counselling.We present the cases of three children and
their families diagnosed with MODY over the past two years. These families
highlight the features of three of the more common MODY subtypes, including two
with novel mutations, one of which segregates in a kindred that is strongly
affected by both MODY and classic autoimmune mediated diabetes. To date, we have
identified a prevalence of MODY in the paediatric diabetes population of the
lower South Island, New Zealand, of approximately 2.5%. This prevalence, along
with increasing access to molecular genetic testing, highlights the importance of
consideration of MODY in atypical diabetes presentations in the
paediatric/adolescent population.
PMID- 24355480
TI - Comparative proteomic study in serum of patients with primary open-angle glaucoma
and pseudoexfoliation glaucoma.
AB - Alterations in the sera proteins between patients with Primary Open-Angle
Glaucoma (POAG), Pseudoexfoliation Glaucoma (PEXG), and healthy controls were
identified through a proven approach utilizing equalization of high-abundance
serum proteins with ProteoMinerTM, two-dimensional fluorescent difference gel
electrophoresis (2D-DIGE), MALDI-TOF/TOF, and nanoLC-MS-MS. Quantitative
immunoassays of the 17 most-differentially-altered proteins identified in this
analysis confirmed that they were also over expressed in the intact serum of
newly recruited glaucoma patients. Overall, this report identifies a panel of
candidates for glaucoma biomarkers and supports their further validation in large
population studies. Additionally, functional pathway analysis of these candidate
proteins suggested that they are part of a network linked to regulating immune
and inflammatory-related processes. The data have been deposited to the
ProteomeXchange with identifier PXD000198. BIOLOGICAL SIGNIFICANCE: POAG and PEXG
are major causes of age-related blindness in the world; however, treatment can be
very effective if they are identified early on in the progression. Genetic
linkage studies can only explain a limited number of cases, suggesting that these
forms of glaucoma are multigenic in nature. Other important factors, such as
modifier genes, epigenetic influences, environmental and dietary agents, and
inflammatory and oxidative effects are also believed to affect the development of
these diseases. The characterization of metabolic and/or proteins changes, for
example in bodily fluids, before the clinical manifestation of glaucoma is of
considerable relevance for its early diagnosis. In the present work,
identification of over-expressed proteins in serum of glaucoma patients (POAG and
PEXG) linked to immune and inflammatory processes supports the finding that
changes in these pathways also manifest systemically in patients with these
pathologies. This study provides a new basis to validate the identified proteins
as biomarkers of glaucoma in a large-scale-multiplexed screening in sera.
PMID- 24355481
TI - Variation in the salivary proteomes of differentially virulent greenbug
(Schizaphis graminum Rondani) biotypes.
AB - Greenbug (Schizaphis graminum Rondani) biotypes are classified by their
differential virulence to wheat, barley, and sorghum varieties possessing
greenbug resistance genes. Virulent greenbug biotypes exert phytotoxic effects
upon their hosts during feeding, directly inducing physiological and metabolic
alterations and accompanying foliar damage. Comparative analyses of the salivary
proteomes of four differentially virulent greenbug biotypes C, E, G, and H showed
significant proteomic divergence between biotypes. Thirty-two proteins were
identified by LC-MS/MS; the most prevalent of which were three glucose
dehydrogenase paralogs (GDH), lipophorin, complementary sex determiner, three
proteins of unknown function, carbonic anhydrase, fibroblast growth factor
receptor, and abnormal oocyte (ABO). Seven nucleotide-binding proteins were
identified, including ABO which is involved in mRNA splicing. Quantitative
variation among greenbug biotypes was detected in six proteins; two GDH paralogs,
carbonic anhydrase, ABO, and two proteins of unknown function. Our findings
reveal that the greenbug salivary proteome differs according to biotype and
diverges substantially from those reported for other aphids. The proteomic
profiles of greenbug biotypes suggest that interactions between aphid salivary
proteins and the plant host result in suppression of plant defenses and cellular
transport, and may manipulate transcriptional regulation in the plant host,
ultimately allowing the aphid to maintain phloem ingestion. BIOLOGICAL
SIGNIFICANCE: Greenbug (Schizaphis graminum Rondani, GB) is a major phytotoxic
aphid pest of wheat, sorghum, and barley. Unlike non-phytotoxic aphids, GB
directly damages its host, causing uniformly characteristic symptoms leading to
host death. As saliva is the primary interface between the aphid and its plant
host, saliva is also the primary aphid biotypic determinant, and differences in
biotypic virulence are the result of biotypic variations in salivary content.
This study analyzed the exuded saliva of four distinct Greenbug biotypes with a
range of virulence to crop lines containing greenbug resistance traits in order
to identify differences between salivary proteins of the examined biotypes. Our
analyses confirmed that the salivary proteomes of the examined greenbug biotypes
differ widely, identified 32 proteins of the greenbug salivary proteome, and
found significant proteomic variation between six identified salivary proteins.
The proteomic variation identified herein is likely the basis of biotypic
virulence, and the proteins identified can serve as the basis for functional
studies into both greenbug-induced phytotoxic damage and into the molecular basis
of virulence in specific GB biotypes. This article is part of a Special Issue
entitled: SI: Proteomics of non-model organisms.
PMID- 24355482
TI - EEG signatures of arm isometric exertions in preparation, planning and execution.
AB - The electroencephalographic (EEG) activity patterns in humans during motor
behaviour provide insight into normal motor control processes and for diagnostic
and rehabilitation applications. While the patterns preceding brisk voluntary
movements, and especially movement execution, are well described, there are few
EEG studies that address the cortical activation patterns seen in isometric
exertions and their planning. In this paper, we report on time and time-frequency
EEG signatures in experiments in normal subjects (n=8), using multichannel EEG
during motor preparation, planning and execution of directional centre-out arm
isometric exertions performed at the wrist in the horizontal plane, in response
to instruction-delay visual cues. Our observations suggest that isometric force
exertions are accompanied by transient and sustained event-related potentials
(ERP) and event-related (de-)synchronisations (ERD/ERS), comparable to those of a
movement task. Furthermore, the ERPs and ERD/ERS are also observed during
preparation and planning of the isometric task. Comparison of ear-lobe-referenced
and surface Laplacian ERPs indicates the contribution of superficial sources in
supplementary and pre-motor (FC(z)), parietal (CP(z)) and primary motor cortical
areas (C1 and FC1) to ERPs (primarily negative peaks in frontal and positive
peaks in parietal areas), but contribution of deep sources to sustained time
domain potentials (negativity in planning and positivity in execution). Transient
and sustained ERD patterns in MU and beta frequency bands of ear-lobe-referenced
and surface Laplacian EEG indicate the contribution of both superficial and deep
sources to ERD/ERS. As no physical displacement happens during the task, we can
infer that the underlying mechanisms of motor-related ERPs and ERD/ERS patterns
do not only depend on change in limb coordinate or muscle-length-dependent
ascending sensory information and are primary generated by motor preparation,
direction-dependent planning and execution of isometric motor tasks. The results
contribute to our understanding of the functions of different brain regions
during voluntary motor tasks and their activity signatures in EEG can shed light
on the relationships between large-scale recordings such as EEG and other
recordings such as single unit activity and fMRI in this context.
PMID- 24355483
TI - Characterization and reduction of cardiac- and respiratory-induced noise as a
function of the sampling rate (TR) in fMRI.
AB - It has recently been shown that both high-frequency and low-frequency cardiac and
respiratory noise sources exist throughout the entire brain and can cause
significant signal changes in fMRI data. It is also known that the brainstem,
basal forebrain and spinal cord areas are problematic for fMRI because of the
magnitude of cardiac-induced pulsations at these locations. In this study, the
physiological noise contributions in the lower brain areas (covering the
brainstem and adjacent regions) are investigated and a novel method is presented
for computing both low-frequency and high-frequency physiological regressors
accurately for each subject. In particular, using a novel optimization algorithm
that penalizes curvature (i.e. the second derivative) of the physiological
hemodynamic response functions, the cardiac- and respiratory-related response
functions are computed. The physiological noise variance is determined for each
voxel and the frequency-aliasing property of the high-frequency cardiac waveform
as a function of the repetition time (TR) is investigated. It is shown that for
the brainstem and other brain areas associated with large pulsations of the
cardiac rate, the temporal SNR associated with the low-frequency range of the
BOLD response has maxima at subject-specific TRs. At these values, the high
frequency aliased cardiac rate can be eliminated by digital filtering without
affecting the BOLD-related signal.
PMID- 24355484
TI - Exposure of fallopian tube epithelium to follicular fluid mimics carcinogenic
changes in precursor lesions of serous papillary carcinoma.
AB - OBJECTIVES: Ovulation-related inflammation is suspected to have a causal role in
ovarian carcinogenesis, but there are no human models to study the molecular
pathways. Our aim is to develop such an ex-vivo model based on human fallopian
tube (FT) epithelium exposed to human follicular fluid (FF). METHODS: FT
epithelium was dissociated from normal surgical specimens. FF was obtained from
donors undergoing in-vitro fertilization. The cells were cultured on collagen
coated Transwells and incubated with FF for various periods of time. The
transcriptomic changes resulting from FF treatment were profiled using Affymetrix
expression arrays. Specific characteristics of the FT pre-cancerous lesions were
studied using immunohistochemistry, immunofluorescence, RT-PCR and XTT assay.
RESULTS: We show that FF exposure causes up-regulation of inflammatory and DNA
repair pathways. Double stranded DNA breaks are induced. There is a minor
increase in cell proliferation. TP53, which is the hallmark of the precursor
lesion in-vivo, is accumulated. Levels of expression and secretion of Interleukin
8 are significantly increased. CONCLUSIONS: Our model addresses the main non
genetic risk factor for ovarian cancer, namely the impact of ovulation. This
study demonstrates the biological implications of in-vitro exposure of human FT
epithelial cells to FF. The model replicates elements characterizing the
precursor lesions of ovarian cancer, and warrants further investigation of the
linkage between repeated exposure to ovulation-related damage and accumulation of
neoplastic changes.
PMID- 24355485
TI - Risk management options elected by women after testing positive for a BRCA
mutation.
AB - OBJECTIVE: To assess the uptake of risk-reducing options for the management of
ovarian and breast cancer risk in BRCA mutation carriers in a large community
based integrated health system in Northern California. METHODS: A retrospective
cohort of deleterious BRCA mutation carriers (1995-2012) was evaluated for
consistency with NCCN guidelines for risk reducing salpingo-oophorectomy (RRSO)
by age of 35-40, risk reducing mastectomy (RRM), as well as surveillance
practices, including pelvic ultrasound, CA 125, mammogram, and breast MRI.
Secondary outcomes included the use of chemoprevention and hormone replacement.
RESULTS: Of the 305 eligible women, 170 were BRCA1 positive, and 135 were BRCA2
positive. Seventy four percent underwent RRSO with only 17% under age 40, while
44% underwent RRM. The median time from the test to both RRSO and RRM was 6
months. In the first year after BRCA diagnosis, 45% underwent a pelvic
ultrasound, dropping to 2.3% by year 5. In year 1, 47% had a CA 125, dropping to
2% by year 5. The number of women undergoing annual MRI and mammogram fell
similarly over time. Sixteen percent of BRCA carriers used oral contraceptives
(OCPs) and only one patient used tamoxifen for chemoprevention. CONCLUSION:
Uptake of RRSO in BRCA carriers in a population based health system is high,
however the majority of women do not have RRSO by the NCCN recommended age.
Compliance with surveillance is low and rapidly declines even 1 year out from
testing. Attention needs to be focused on the earlier identification of BRCA
mutation carriers with consolidated and standardized care to improve risk
reduction.
PMID- 24355486
TI - Biology of IL-36 cytokines and their role in disease.
AB - IL-36alpha, IL-36beta, IL-36gamma, and IL-36Ra, collectively called IL-36
cytokines, are part of the IL-1 family. IL-36alpha, IL-36beta, and IL-36gamma are
IL-36 receptor (IL-36R) agonists, while IL-36Ra is a receptor antagonist that
blocks the activation of IL-36R signaling. IL-36 cytokines require processing in
order to become fully active, however the protease(s) responsible for this are
currently not known. The IL-36 receptor pathway activates dendritic cells and
plays a role in polarizing T-helper responses. The skin is the predominant site
where IL-36 cytokines are expressed and several reports have established that
they play a significant role in the pathogenesis of skin diseases. In this review
the discovery and biological function of the cytokines IL-36alpha, IL-36beta, IL
36gamma and IL-36Ra will be discussed, and their role in the pathogenesis of a
wide variety of diseases.
PMID- 24355487
TI - COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the
incidence of arthralgia, and compliance within the first year of adjuvant
anastrozole therapy.
AB - BACKGROUND: This prospective study evaluated the relationship between arthralgia
and compliance during the first year of adjuvant anastrozole therapy in
postmenopausal women with hormone receptor-positive early breast cancer. PATIENTS
AND METHODS: COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open
label, multicenter, noninterventional study conducted in Germany. Patients had
started adjuvant anastrozole 3-6 months before the study start. The primary end
points were arthralgia, compliance, and the relationship between compliance and
arthralgia, assessed at specific time points. RESULTS: Overall, 1916 patients
received upfront anastrozole. Mean arthralgia scores were increased from baseline
at each visit up to 9 months. Compliance with anastrozole therapy gradually
decreased over time from baseline to 9 months (P<0.001). At 9 months,
investigators estimated that >95% of patients were compliant versus patient
reports of <70%. There was a significant association between arthralgia mean
scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall
(P<0.0001). Over time, new events or impairment of existing arthralgias were
reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients.
CONCLUSION: Arthralgia is important in the clinical management of women with
early breast cancer and may contribute to noncompliance and clinical outcomes.
CLINICALTRIALSGOV IDENTIFIER: NCT00857012.
PMID- 24355488
TI - Stereotactic radiotherapy for oligometastatic cancer: a prognostic model for
survival.
AB - BACKGROUND: Stereotactic radiotherapy (SRT) is a safe and locally effective
treatment for patients with inoperable oligometastases. The challenge remains
identifying subsets of patients that benefit in terms of overall survival (OS).
PATIENTS AND METHODS: Between 2005 and 2011, 309 patients with <=5 metastases
were treated by stereotactic body radiotherapy (n=209) and/or by intracranial
single or fractionated stereotactic radiotherapy (n=107). We analyzed OS and
carried out a risk factor analysis. RESULTS: The median survival of all patients
was 24 months. The 3-, 4- and 5-year OS rates were 32%, 25% and 19%,
respectively. The following four risk factors were independently associated with
impaired OS: nonadenocarcinoma histology (P<0.01), intracranial metastases
(P<0.01), synchronous oligometastatic disease (P<0.01) and male gender (P=0.02).
Patients with 0, 1 and 2 risk factors displayed a median survival (95% CI) of 40
(24-63), 29 (23-35) and 23 (16-29) months, respectively, and are defined as
patients with good prognosis. Patients with 3 and 4 risk factors had a median
survival of 9 (6-11) and 4 (1-7) months only and are defined as bad prognostic
patients. CONCLUSIONS: We identified subsets of oligometastatic cancer patients
with good prognosis after SRT. These patients are candidates for inclusion in
prospective randomized trials for defining the role of SRT in the management of
oligometastases.
PMID- 24355489
TI - A multi-modality platform to image stem cell graft survival in the naive and
stroke-damaged mouse brain.
AB - Neural stem cell implantations have been extensively investigated for treatment
of brain diseases such as stroke. In order to follow the localization and
functional status of cells after implantation noninvasive imaging is essential.
Therefore, we developed a comprehensive multi-modality platform for in vivo
imaging of graft localization, density, and survival using 19F magnetic resonance
imaging in combination with bioluminescence imaging. We quantitatively analyzed
cell graft survival over the first 4 weeks after transplantation in both healthy
and stroke-damaged mouse brain and correlated our findings of graft vitality with
the host innate immune response. The multi-modality imaging platform will help to
improve cell therapy also in context other than stroke and to gain indispensable
information for clinical translation.
PMID- 24355490
TI - Application of a theoretical framework for behavior change to hospital workers'
real-time explanations for noncompliance with hand hygiene guidelines.
AB - BACKGROUND: Insufficient use of behavioral theory to understand health care
workers' (HCWs) hand hygiene compliance may result in suboptimal design of hand
hygiene interventions and limit effectiveness. Previous studies examined HCWs'
intended, rather than directly observed, compliance and/or focused on just 1
behavioral model. This study examined HCWs' explanations of noncompliance in
"real time" (immediately after observation), using a behavioral theory framework,
to inform future intervention design. METHODS: HCWs were directly observed and
asked to explain episodes of noncompliance in "real-time." Explanations were
recorded, coded into 12 behavioral domains, using the Theory Domains Framework,
and subdivided into themes. RESULTS: Over two-thirds of 207 recorded explanations
were explained by 2 domains. These were "Memory/Attention/Decision Making" (87,
44%), subdivided into 3 themes (memory, loss of concentration, and distraction by
interruptions), and "Knowledge" (55, 26%), with 2 themes relating to specific
hand hygiene indications. No other domain accounted for more than 18 (9%)
explanations. CONCLUSION: An explanation of HCW's "real-time" explanations for
noncompliance identified "Memory/Attention/Decision Making" and "Knowledge" as
the 2 behavioral domains commonly linked to noncompliance. This suggests that
hand hygiene interventions should target both automatic associative learning
processes and conscious decision making, in addition to ensuring good knowledge.
A theoretical framework to investigate HCW's "real-time" explanations of
noncompliance provides a coherent way to design hand hygiene interventions.
PMID- 24355491
TI - The role of infection prevention conferences to build and maintain knowledge
sharing networks: a longitudinal evaluation.
AB - Well-connected knowledge-sharing networks (KSNs) of infection preventionists are
vital to the profession. Face-to-face networking during conferences is considered
critical to build and maintain KSNs; however, this has never been formally
studied. We used a pre-post survey design to evaluate the effect of a regional
infection prevention meeting on the KSNs. We found that the meeting did not alter
the KSNs of infection preventionists. Current meeting structures should be re
evaluated with a goal to improve KSNs.
PMID- 24355492
TI - Accuracy of a radiofrequency identification (RFID) badge system to monitor hand
hygiene behavior during routine clinical activities.
AB - BACKGROUND: Hand hygiene (HH) is a critical part of infection prevention in
health care settings. Hospitals around the world continuously struggle to improve
health care personnel (HCP) HH compliance. The current gold standard for
monitoring compliance is direct observation; however, this method is time
consuming and costly. One emerging area of interest involves automated systems
for monitoring HH behavior such as radiofrequency identification (RFID) tracking
systems. METHODS: To assess the accuracy of a commercially available RFID system
in detecting HCP HH behavior, we compared direct observation with data collected
by the RFID system in a simulated validation setting and to a real-life clinical
setting over 2 hospitals. RESULTS: A total of 1,554 HH events was observed.
Accuracy for identifying HH events was high in the simulated validation setting
(88.5%) but relatively low in the real-life clinical setting (52.4%). This
difference was significant (P < .01). Accuracy for detecting HCP movement into
and out of patient rooms was also high in the simulated setting but not in the
real-life clinical setting (100% on entry and exit in simulated setting vs 54.3%
entry and 49.5% exit in real-life clinical setting, P < .01). CONCLUSION: In this
validation study of an RFID system, almost half of the HH events were missed.
More research is necessary to further develop these systems and improve accuracy
prior to widespread adoption.
PMID- 24355493
TI - White matter correlates of cognitive inhibition during development: a diffusion
tensor imaging study.
AB - Inhibitory control and cognitive flexibility are two key executive functions that
develop in childhood and adolescence, increasing one's capacity to respond
dynamically to changing external demands and refrain from impulsive behaviors.
These gains evolve in concert with significant brain development. Magnetic
resonance imaging studies have identified numerous frontal and cingulate cortical
areas associated with performance on inhibition tasks, but less is known about
the involvement of the underlying anatomical connectivity, namely white matter.
Here we used diffusion tensor imaging (DTI) to examine correlations between a DTI
derived parameter, fractional anisotropy (FA) of white matter, and performance on
the NEPSY-II Inhibition test (Naming, Inhibition and Switching conditions) in 49
healthy children aged 5-16years (20 females; 29 males). First, whole brain voxel
based analysis revealed several clusters in the frontal projections of the corpus
callosum, where higher FA was associated with worse inhibitory performance, as
well as several clusters in posterior brain regions and one in the brainstem
where higher FA was associated with better cognitive flexibility (in the
Switching task), suggesting a dichotomous relationship between FA and these two
aspects of cognitive control. Tractography through these clusters identified
several white matter tracts, which were then manual traced in native space.
Pearson's correlations confirmed associations between higher FA of frontal
projections of the corpus callosum with poorer inhibitory performance
(independent of age), though associations with Switching were not significant.
Post-hoc evaluation suggested that FA of orbital and anterior frontal projections
of the corpus callosum also mediated performance differences across conditions,
which may reflect differences in self-monitoring or strategy use. These findings
suggest a link between the development of inhibition and cognitive control with
that of the underlying white matter, and may help to identify deviations of
neurobiology in adolescent psychopathology.
PMID- 24355494
TI - Single unit activity of the suprachiasmatic nucleus and surrounding neurons
during the wake-sleep cycle in mice.
AB - The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a
circadian clock for timing of diverse neuronal, endocrine, and behavioral
rhythms, such as the cycle of sleep and wakefulness. Using extracellular single
unit recordings, we have determined, for the first time, the discharge activity
of individual SCN neurons during the complete wake-sleep cycle in non
anesthetized, head restrained mice. SCN neurons (n=79) were divided into three
types according to their regular (type I; n=38) or irregular (type II; n=19)
discharge activity throughout the wake-sleep cycle or their quiescent activity
during waking and irregular discharge activity during sleep (type III; n=22). The
type I and II neurons displayed a long-duration action potential, while the type
III neurons displayed either a short-duration or long-duration action potential.
The type I neurons discharged exclusively as single isolated spikes, whereas the
type II and III neurons fired as single isolated spikes, clusters, or bursts. The
type I and II neurons showed wake-active, wake/paradoxical (or rapid eye
movement) sleep-active, or state-unrelated activity profiles and were,
respectively, mainly located in the ventral or dorsal region of the SCN. In
contrast, the type III neurons displayed sleep-active discharge profiles and were
mainly located in the lateral region of the SCN. The majority of type I and II
neurons tested showed an increase in discharge rate following application of
light to the animal's eyes. Of the 289 extra-SCN neurons recorded, those
displaying sleep-active discharge profiles were mainly located dorsal to the SCN,
whereas those displaying wake-active discharge profiles were mainly located
lateral or dorsolateral to the SCN. This study shows heterogeneity of mouse SCN
and surrounding anterior hypothalamic neurons and suggests differences in their
topographic organization and roles in mammalian circadian rhythms and the
regulation of sleep and wakefulness.
PMID- 24355495
TI - Modulation of synaptic transmission by adenosine in layer 2/3 of the rat visual
cortex in vitro.
AB - Adenosine is a wide-spread endogenous neuromodulator. In the central nervous
system it activates A1 and A2A receptors (A1Rs and A2ARs) which have differential
distributions, different affinities to adenosine, are coupled to different G
proteins, and have opposite effects on synaptic transmission. Although effects of
adenosine are studied in detail in several brain areas, such as the hippocampus
and striatum, the heterogeneity of the effects of A1R and A2AR activation and
their differential distribution preclude generalization over brain areas and cell
types. Here we study adenosine's effects on excitatory synaptic transmission to
layer 2/3 pyramidal neurons in slices of the rat visual cortex. We measured
effects of bath application of adenosine receptor ligands on evoked excitatory
postsynaptic potentials (EPSPs), miniature excitatory postsynaptic potentials
(mEPSPs), and membrane properties. Adenosine reduced the amplitude of evoked
EPSPs and excitatory postsynaptic currents (EPSCs), and reduced frequency of
mEPSPs in a concentration-dependent and reversible manner. Concurrent with EPSP/C
amplitude reduction was an increase in the paired-pulse ratio. These effects were
blocked by application of the selective A1R antagonist DPCPX (8-cyclopentyl-1,3
dipropylxanthine), suggesting that activation of presynaptic A1Rs suppresses
excitatory transmission by reducing release probability. Adenosine (20MUM)
hyperpolarized the cell membrane from -65.3+/-1.5 to -67.7+/-1.8mV, and reduced
input resistance from 396.5+/-44.4 to 314.0+/-36.3MOhm (~20%). These effects were
also abolished by DPCPX, suggesting postsynaptic A1Rs. Application of the
selective A2AR antagonist SCH-58261 (2-(2-furanyl)-7-(2-phenylethyl)-7H
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-a-mine) on the background of
high adenosine concentrations revealed an additional decrease in EPSP amplitude.
Moreover, application of the A2AR agonist CGS-21680 (4-[2-[[6-amino-9-(N-ethyl
beta-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid
hydrochloride) led to an A1R-dependent increase in mEPSP frequency. Dependence of
the A2AR effects on the A1R availability suggests interaction between these
receptors, whereby A2ARs exert their facilitatory effect on synaptic transmission
by inhibiting the A1R-mediated suppression. Our results demonstrate functional
pre and postsynaptic A1Rs and presynaptic A2ARs in layer 2/3 of the visual
cortex, and suggest interaction between presynaptic A2ARs and A1Rs.
PMID- 24355496
TI - Protection of granulocyte-colony stimulating factor to hemorrhagic brain injuries
and its involved mechanisms: effects of vascular endothelial growth factor and
aquaporin-4.
AB - Granulocyte-colony stimulating factor (G-CSF) has protective effects on many
neurological diseases. Here, we aimed to test G-CSF's effects on perihematomal
tissue injuries following intracerebral hemorrhage (ICH) and examine whether the
effects were functionally dependent on vascular endothelial growth factor (VEGF)
and aquaporin-4 (AQP4). We detected the expression of perihematomal VEGF, VEGF
receptors (VEGFRs) and AQP4 at 1, 3 and 7days after ICH. Also, we examined the
effects of G-CSF on tissue injuries by ICH in wild type mice, and tested whether
such effects were VEGF and AQP4 dependent by using VEGFR inhibitor - SU5416 and
AQP4 knock-out (AQP4(-/-)) mice. Furthermore, we assessed the related signal
transduction pathways via astrocyte cultures. We found G-CSF highly increased
perihematomal VEGF, VEGFR-2 and AQP4. Importantly, G-CSF led to neurological
functional improvement in both types of mice by associating with reduction of
brain edema, blood-brain barrier (BBB) permeability and neuronal death and
apoptosis and statistical analysis suggested AQP4 was required for these effects.
Besides, except BBB leakage alleviation, the above effects were attenuated but
not counteracted by SU5416, suggesting involvement of VEGF. G-CSF up-regulated
phosphorylation of extracellular signal-regulated kinase (ERK) and signal
transducer and activator of transcription 3 (STAT3) as well as VEGF and AQP4
proteins in cultured astrocytes. The latter was inhibited by ERK and STAT3
inhibitors respectively. Our data suggest the protective effects of G-CSF on
perihematomal tissue injuries after ICH are highly associated with the increased
levels of VEGF and AQP4, possibly act through C-Jun amino-terminal kinase and ERK
pathways respectively.
PMID- 24355498
TI - Targeted interventions of ultra-poor women in rural Rangpur, Bangladesh: do they
make a difference to appropriate cooking practices, food habits and sanitation?
AB - This study aimed to assess whether teaching good cooking practices, food habits
and sanitation to ultra-poor rural women in four rural communities of Rangpur
district, Bangladesh, with a high density of extremely poor households, would
improve the overall health of the community. The sample size was 200 respondents
combined from the target and control areas. In the target area, twelve in-depth
interviews and four focus group discussions were undertaken for knowledge
dissemination. Descriptive and mixed-model analyses were performed. The results
show that washing hands with soap was 1.35 times more likely in the target than
the control group (p<0.01). Further, after intervention, there was a significant
improvement in hand-washing behaviour: before cutting vegetables, preparing food,
feeding a child and eating, and after defecating and cleaning a baby (p<0.05).
Also, the target group was more likely to moderately and briefly boil their
vegetables and were 19% less likely to use maximum heat when cooking vegetables
than the control group (p<0.01). Improved knowledge and skills training of ultra
poor women reduces the loss of nutrients during food preparation and increases
their hygiene through hand-washing in every-day life.
PMID- 24355499
TI - Mutual structural effect of bilirubin and model membranes by vibrational circular
dichroism.
AB - In this study, vibrational circular dichroism (VCD) spectroscopy was employed for
the first time to study the bilirubin (BR) interaction with model membranes and
models for membrane proteins. An enantioselective interaction of BR with
zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and sphingomyelin
(SPM) liposomes was observed by VCD and electronic circular dichroism (ECD)
complemented by absorption and fluorescence spectroscopy. The M-form of BR was
preferentially recognized in the BR/DMPC system at concentration above 1*10(-4)M,
for lower concentrations the P-form of BR was recognized by the DMPC liposomes.
The VCD spectra also showed that the SPM liposomes, which represent the main
component of nerve cell membrane, were significantly more disturbed by the
presence of BR than the DMPC liposomes-a stable association with a strong VCD
signal was observed providing the explanations for the supposed BR neurotoxicity.
The effect of time and pH on the BR/DMPC or SPM liposome systems was shown to be
essential while the effect of temperature in the range of 15-70 degrees C was
negligible demonstrating the surprisingly high temperature stability of BR when
interacting with the studied membranes. The influence of a membrane protein was
tested on a model consisting of poly-l-arginine (PLAG) bound in the alpha-helical
form to the surface of 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol)
liposomes and sodium dodecyl sulfate micelles. VCD and also ECD spectra showed
that a variety of BR diastereoisomers interacted with PLAG in such systems. In a
system of PLAG with micelles composed of sodium dodecyl sulfate, the M-form of
bound BR was observed.
PMID- 24355500
TI - Sequential anaerobic-aerobic treatment of pharmaceutical wastewater with high
salinity.
AB - In this study, pharmaceutical wastewater with high total dissolved solids (TDSs)
and chemical oxygen demand (COD) content was treated through a sequential
anaerobic-aerobic treatment process. For the anaerobic process, an up-flow
anaerobic sludge blanket (UASB) was applied, and a COD removal efficiency of
41.3+/-2.2% was achieved with an organic loading rate of 8.11+/-0.31gCOD/L/d and
a hydraulic retention time of 48h. To evaluate the salinity effect on the
anaerobic process, salts in the wastewater were removed by ion exchange resin,
and adverse effect of salinity was observed with a TDS concentration above
14.92g/L. To improve the anaerobic effluent quality, the UASB effluent was
further treated by a membrane bioreactor (MBR) and a sequencing batch reactor
(SBR). Both the UASB+MBR and UASB+SBR systems achieved excellent organic removal
efficiency, with respective COD removal of 94.7% and 91.8%. The UASB+MBR system
showed better performance in both organic removal and nitrification.
PMID- 24355501
TI - Process energy comparison for the production and harvesting of algal biomass as a
biofuel feedstock.
AB - Harvesting and drying are often described as the most energy intensive stages of
microalgal biofuel production. This study analyzes two cultivation and eleven
harvest technologies for the production of microalgae biomass with and without
the use of drying. These technologies were combined to form 122 different
production scenarios. The results of this study present a calculation methodology
and optimization of total energy demand for the production of algal biomass for
biofuel production. The energetic interaction between unit processes and total
process energy demand are compared for each scenario. Energy requirements are
shown to be highly dependent on final mass concentration, with thermal drying
being the largest energy consumer. Scenarios that omit thermal drying in favor of
lipid extraction from wet biomass show the most promise for energy efficient
biofuel production. Scenarios which used open ponds for cultivation, followed by
settling and membrane filtration were the most energy efficient.
PMID- 24355497
TI - Adipokines: a link between obesity and cardiovascular disease.
AB - Obesity is a risk factor for various cardiovascular diseases including
hypertension, atherosclerosis, and myocardial infarction. Recent studies aimed at
understanding the microenvironment of adipose tissue and its impact on systemic
metabolism have shed light on the pathogenesis of obesity-linked cardiovascular
diseases. Adipose tissue functions as an endocrine organ by secreting multiple
immune-modulatory proteins known as adipokines. Obesity leads to increased
expression of pro-inflammatory adipokines and diminished expression of anti
inflammatory adipokines, resulting in the development of a chronic, low-grade
inflammatory state. This adipokine imbalance is thought to be a key event in
promoting both systemic metabolic dysfunction and cardiovascular disease. This
review will focus on the adipose tissue microenvironment and the role of
adipokines in modulating systemic inflammatory responses that contribute to
cardiovascular disease.
PMID- 24355502
TI - A new hybrid treatment system of bioreactors and electrocoagulation for superior
removal of organic and nutrient pollutants from municipal wastewater.
AB - This paper evaluated a novel pilot scale hybrid treatment system which combines
rotating hanging media bioreactor (RHMBR), submerged membrane bioreactor (SMBR)
along with electrocoagulation (EC) as post treatment to treat organic and
nutrient pollutants from municipal wastewater. The results indicated that the
highest removal efficiency was achieved at the internal recycling ratio as 400%
of the influent flow rate which produced a superior effluent quality with
0.26mgBOD5L(-1), 11.46mgCODCrL(-1), 0.00mgNH4(+)-NL(-1), and 3.81mgT-NL(-1),
0.03mgT-PL(-1). During 16months of operation, NH4(+)-N was completely eliminated
and T-P removal efficiency was also up to 100%. It was found that increasing in
internal recycling ratio could improve the nitrate and nitrogen removal
efficiencies. Moreover, the TSS and coliform bacteria concentration after
treatment was less than 5mgL(-1) and 30MPNmL(-1), respectively, regardless of
internal recycling ratios and its influent concentration.
PMID- 24355503
TI - Digestion and dewatering characteristics of waste activated sludge treated by an
anaerobic biofilm system.
AB - Immobilization of microorganisms for sludge anaerobic digestion was investigated
in this study. The effects of filler properties on anaerobic digestion and
dewaterability of waste activated sludge were assessed at mesophilic temperature
in batch mode. The results showed that the duration of the methanogenic stage of
reactors without filler, with only filler, and with pre-incubated filler was
39days, 19days and 13days, respectively, during which time the protein was
degraded by 45.0%, 29.4% and 30.0%, and the corresponding methane yield was
193.9, 107.2 and 108.2mL/g volatile suspended solids added, respectively. On day
39, the final protein degradation efficiency of the three reactors was 45.0%,
40.9% and 42.0%, respectively. The results of normalized capillary suction time
and specific resistance to filtration suggested that the reactor incorporating
pre-incubated filler could improve the dewaterability of digested sludge, while
the effect of the reactor incorporating only filler on sludge dewaterability was
uncertain.
PMID- 24355504
TI - Mining and assessment of catabolic pathways in the metagenome of a common
effluent treatment plant to induce the degradative capacity of biomass.
AB - Metagenome analysis was used to understand the microbial community in activated
sludge treating industrial wastewaters at a Common Effluent Treatment Plant
(CETP) in South India. The taxonomic profile mapped onto National Center for
Biotechnology Information (NCBI) taxonomy using MEtaGenome ANalyzer (MEGAN),
demonstrated that the most abundant domain belonged to prokaryotes, dominated by
bacteria. Bacteria representing nine phyla were identified from the sequence data
including representatives from two new phyla, Synergistetes and Elusimicrobia.
Functional analysis of the metagenome, with specific reference to the metabolism
of aromatic compounds, revealed the dominance of genes of the central meta
cleavage pathway. This information was used to improve the degradative efficiency
in the wastewater treatment plant. A pilot scale plant was set up with 200L of
activated sludge using salicylate induced sludge and results demonstrated 52%
removal in chemical oxygen demand (COD) against non-induced biomass.
PMID- 24355506
TI - Denture stomatitis and salivary vascular endothelial growth factor in immediate
complete denture wearers with type 2 diabetes.
AB - STATEMENT OF PROBLEM: Diabetes mellitus type 2 is associated with a variety of
oral mucosal changes, including an altered level of salivary vascular endothelial
growth factor. However, the authors identified no studies concerning denture
stomatitis and salivary vascular endothelial growth factor in immediate denture
wearers with diabetes mellitus type 2. PURPOSE: The purpose of this study was to
investigate the incidence of and risk factors for denture stomatitis in immediate
complete denture wearers with and without diabetes mellitus type 2 and to
investigate the relationship between levels of salivary vascular endothelial
growth factor and clinical forms of denture stomatitis in both groups. MATERIAL
AND METHODS: Individuals without diabetes (n=42) or with diabetes mellitus type 2
(n=36) who were candidates for complete immediate dentures were included in the
study. After 1 year of wearing relined immediate dentures, participants were
evaluated for denture stomatitis and potential contributing factors. Salivary
vascular endothelial growth factor levels were measured with enzyme-linked
immunosorbent assays. Data were analyzed with the chi(2) test or the Student t
test where appropriate, as well as with binary logistic regression analysis.
RESULTS: The incidence of denture stomatitis was 61% in participants with
diabetes mellitus type 2 and 38% in those without diabetes. Low denture stability
and diabetes mellitus type 2 were risk factors for denture stomatitis. Salivary
vascular endothelial growth factor concentrations at the beginning of the study
were 557.6 +/-94.7 pg/mL in participants with diabetes mellitus type 2 and 103.5
+/-21.6 pg/mL in those without diabetes. In Newton Type I and Newton Type II
denture stomatitis, vascular endothelial growth factor levels were 460.9 +/-55.4
pg/mL and 1445.2 +/-422.1 pg/mL in individuals with diabetes and 73.2 +/-10.0
pg/mL and 306.5 +/-22.6 pg/mL in those without diabetes. CONCLUSIONS: Perceived
denture stability and diabetes mellitus type 2 are independent risk factors for
the occurrence of denture stomatitis. Altered salivary vascular endothelial
growth factor levels and denture stomatitis are more prevalent in denture wearers
with diabetes mellitus type 2.
PMID- 24355505
TI - Shear bond strength of self-adhesive resin cements to base metal alloy.
AB - STATEMENT OF PROBLEM: Many self-adhesive cements have been introduced in the past
few years, with little or no data regarding their clinical performance. This
study investigated the shear bond strength of some recently introduced self
adhesive resin cements. PURPOSE: The purpose of this study was to evaluate the
shear bond strength of self-adhesive and conventional resin-based cements to a
base metal alloy. MATERIAL AND METHODS: Four groups (10-12 each) that comprised 3
self-adhesive cements (SmartCem2; RelyX Unicem; seT SDI) and a conventional resin
based cement (RelyX ARC) were tested. Cylindrical cement specimens (diameter, 3
mm; height, 3 mm) were applied to nickel-free base metal alloy (Sheradent) disks
with a diameter of 12 mm, and the surface was treated with airborne-particle
abrasion of 50 MUm aluminum oxide. The metal disks were fixed in brass molds
specifically designed for the shear bond test device. Test specimens were
incubated at 37 degrees C for 24 hours and then the shear bond was tested with a
Zwick Roll testing machine at a 0.8 mm/min cross-head speed. In addition, bond
failures were investigated and categorized as adhesive, cohesive, or mixed. Shear
bond strengths were calculated by dividing the maximum debonding force over the
cross-sectional area of each specimen. One-way ANOVA and the Tukey (honestly
significant difference) post hoc test were used to test statistical significant
differences among the groups (alpha=.05). RESULTS: Statistical analysis showed
significant differences among different resin cements (F=14.34, P<.001). The
highest mean shear bond strength was observed for SmartCem2 (14.18 MPa), and the
lowest was reported for seT (3.52 MPa). The observed failure mode in all the
materials was adhesive in nature, which occurred at the resin-metal interface.
CONCLUSIONS: The early bond strength of self-adhesive resin cements varied
significantly among the tested materials. SmartCem2 showed the highest bond
strength, which was 4 times the strength observed for seT SDI.
PMID- 24355507
TI - Effect of storage times and mechanical load cycling on dentin bond strength of
conventional and self-adhesive resin luting cements.
AB - STATEMENT OF PROBLEM: The lack of long-term bond stability between resin cements
and dentin may compromise the success of indirect restorations. PURPOSE: The
purpose of this study was to evaluate the effects of long-term storage in
artificial saliva and mechanical load cycling on the microtensile bond strength
of conventional and self-adhesive resin cements to dentin. MATERIAL AND METHODS:
The occlusal dentin surfaces of 128 human molars were exposed and flattened. The
teeth were assigned to 16 groups (n=8) according to resin cement and in vitro
aging strategy. Two self-adhesive resin cements (RelyX Unicem and Clearfil SA
Cement) and 2 conventional cementing systems (RelyX ARC and Clearfil Esthetic
Cement) were used. Resin cements were applied to prepolymerized indirect resin
disks, which were bonded to the dentin surfaces and light polymerized. The
control groups were represented by immediate microtensile bond strength (24
hours) and aging methods were performed with mechanical load cycling or storage
in artificial saliva (1 year and 2 years). Bonded beams were tested in tension
until failure. Data (MPa) were analyzed by Proc Mixed for repeated measures and
the Tukey-Kramer test (alpha=.05). RESULTS: The self-adhesive resin cements
exhibited higher microtensile bond strength than conventional cementing systems
for all conditions studied. The microtensile bond strength of RelyX ARC and self
adhesive resin cements did not decrease after storage in artificial saliva and
mechanical load cycling. The Clearfil Esthetic Cement showed the lowest
microtensile bond strength and a significant reduction after 2 years of storage
in artificial saliva. CONCLUSIONS: The storage times and mechanical load cycling
did not affect the microtensile bond strength of self-adhesives and RelyX ARC
resin cements. The highest microtensile bond strength was obtained for self
adhesive resin cements, with no significant difference between them.
PMID- 24355508
TI - Risk factors for denture-related oral mucosal lesions in a geriatric population.
AB - STATEMENT OF PROBLEM: Denture-related mucosal lesions have been broadly studied.
However, no consensus has been reached regarding the risk factors associated with
these lesions, and few studies have used multivariable analysis to determine the
relative significance of different risks. PURPOSE: The purpose of this study was
to determine the relationship between systemic, local, and denture factors on the
risk of denture-related oral mucosal lesions in an elderly population by using
multivariable analysis. MATERIAL AND METHODS: Eighty-four elderly denture wearers
recruited from geriatric residences and day care centers participated in this
cross-sectional study. All data were obtained by means of a questionnaire
interview, a physical examination, and complementary tests. Bivariate
relationship and multiple logistic regression analyses were performed
(alpha=.05). RESULTS: Angular cheilitis (34%), traumatic ulcers (15%), and
denture stomatitis (14%) were the 3 most common lesions, and the prevalence of at
least 1 denture-related mucosal lesion was 54%. The presence of denture
stomatitis was related to low saliva pH, never having smoked, and regular sugar
consumption. Angular cheilitis was associated with age, complete edentulism, the
presence of oral Candida, a lack of denture stability, and a reduced occlusal
vertical dimension. The presence of traumatic ulcers was related to a resorbed
residual alveolar ridge. The presence of at least 1 lesion was associated with
poor masticatory efficiency, being resident in a care facility, oral Candida, and
a lack of denture stability. CONCLUSIONS: Several systemic, local, and denture
related characteristics are independent risk factors for denture-related mucosal
lesions in an elderly population.
PMID- 24355509
TI - Experimental study of the removal force in tapered implant-abutment interfaces: a
pilot study.
AB - STATEMENT OF PROBLEM: Conically tapered interface fits (TIF) provide a reliable
and strong self-locking mechanism between a dental implant and its matching
abutment. On occasion, it may be necessary to remove the abutment for maintenance
purposes. The removal of an indexed implant with a TIF-type connection requires
the application of a (removal) force to overcome the friction force due to
preload. PURPOSE: The purpose of this study was to measure the removal force
needed to extract the abutment from the implant in TIF-type connections. MATERIAL
AND METHODS: A workbench was designed and built to measure the forces involved in
the abutment removal process. Experiments were conducted to test the removal
force (F(R)) for 20 conical interfaces specifically built for the study. The
effects of the preload magnitude (F(P)) and the difference between the taper
angles of the implant and the abutment (taper mismatch) were investigated
experimentally and theoretically. A 2-way factorial ANOVA and regression analysis
was used to evaluate the variability in the process and the influence of the 2
variables considered in the experiments (alpha=.05). RESULTS: Experiments
revealed that the (F(R)-F(P)) ratio decreases with the preload F(P), whereas the
influence of the taper mismatch cannot be clearly stated. CONCLUSIONS: The
removal force increases with increasing preload and the F(R)-F(P) ratio varies
widely. This variability is attributed to the variability of the friction
coefficient, and it can influence implant-removal applications because the
removal force can be, in some restorations, as large as 40% of the preload.
PMID- 24355510
TI - Mechanical behavior of dental implants in different positions in the
rehabilitation of the anterior maxilla.
AB - STATEMENT OF PROBLEM: In dental rehabilitations that involve implants, the number
of implants is sometimes smaller than the number of lost teeth. This fact can
affect the biomechanical behavior and success of the implants. PURPOSE: The
purpose of this study was to investigate the mechanical behavior of different
implant positions in the rehabilitation of the anterior maxilla. MATERIAL AND
METHODS: Three-dimensional models of the maxilla were created based on computed
tomography images for 3 different anterior prosthetic rehabilitations. In group
IL, the implants were placed in the lateral incisor positions with pontics in the
central incisor positions; in group IC, the implants were in the central incisor
positions with cantilevers in the lateral incisor positions; and, in group ILIC,
one implant was in a lateral incisor position and one was in a central incisor
position, with a pontic and a cantilever in the remaining positions. A 150 N load
was distributed and applied at the center of the palatal surface of each tooth at
a 45-degree angle to the long axis of the tooth. The resulting stress-strain
distribution was analyzed for each group. RESULTS: The lowest displacement of the
prosthetic structure was observed in group IC, although the same group exhibited
the largest displacement of the bone tissue. In the bone tissue, the von Mises
stress was mainly observed in the cortical bone in all groups. The maximum value
of the von Mises stress shown in the cortical tissue was 35 MPa in the implant
that neighbors the cantilever in group ILIC. The maximum von Mises stress in the
trabecular bone was 3.5 MPa. CONCLUSION: The prosthetic configuration of group IC
limited the displacement of the prosthetic structure but led to greater
displacement of the bone structure. The use of a cantilever increased the stress
concentration in the implant and in the bone structure adjacent to the cantilever
under the conditions studied here.
PMID- 24355511
TI - An approach to biomimetics: the natural CAD/CAM restoration: a clinical report.
AB - Those in the dental field have always pursued the perfect dental material for the
treatment of compromised teeth. Gold, amalgam, composite resin, glass ionomer,
and porcelain have been used. Tooth-like restorative materials (composite resin
and porcelain) combined with an effective hard tissue bond have met the growing
demand for esthetic or metal-free restorations in the past 15 to 20 years.
However, none of those materials can fully mimic the unique properties of dentin
(compliance and crack-stopping behavior) and enamel (wear resistance, function).
The aim of this article is to report the restoration of an extensively damaged
tooth with a natural restoration obtained by milling an extracted third molar
tooth with a computer-aided design and computer-aided manufacturing (CAD/CAM)
system. The main benefit of this novel technique is the replacement of lost
tissues by actual enamel and dentin, with the potential to recover mechanical,
esthetic, and biologic properties. The indication for extracting third molars and
premolars because of impaction or for orthodontic reasons makes these posterior
teeth readily available. The innovation of the method presented here is the
optimal use of the extracted tooth substrate thanks to its positioning technique
in the CAD/CAM milling chamber.
PMID- 24355512
TI - Multi-technique approach to assess the effects of microbial biofilms involved in
copper plumbing corrosion.
AB - Microbially influenced corrosion (MIC) is recognized as an unusual and severe
type of corrosion that causes costly failures around the world. A microbial
biofilm could enhance the copper release from copper plumbing into the water by
forming a reactive interface. The biofilm increases the corrosion rate, the
mobility of labile copper from its matrix and the detachment of particles
enriched with copper under variable shear stress due to flow conditions. MIC is
currently considered as a series of interdependent processes occurring at the
metal-liquid interface. The presence of a biofilm results in the following
effects: (a) the formation of localized microenvironments with distinct pH,
dissolved oxygen concentrations, and redox conditions; (b) sorption and
desorption of labile copper bonded to organic compounds under changing water
chemistry conditions; (c) change in morphology by deposition of solid corrosion
by-products; (d) diffusive transport of reactive chemical species from or towards
the metal surface; and (e) detachment of scale particles under flow conditions.
Using a multi-technique approach that combines pipe and coupon experiments this
paper reviews the effects of microbial biofilms on the corrosion of copper
plumbing systems, and proposes an integrated conceptual model for this phenomenon
supported by new experimental data.
PMID- 24355513
TI - Corrosion of low carbon steel by microorganisms from the 'pigging' operation
debris in water injection pipelines.
AB - Present in all environments, microorganisms develop biofilms adjacent to the
metallic structures creating corrosion conditions which may cause production
failures that are of great economic impact to the industry. The most common
practice in the oil and gas industry to annihilate these biofilms is the
mechanical cleaning known as "pigging". In the present work, microorganisms from
the "pigging" operation debris are tested biologically and electrochemically to
analyse their effect on the corrosion of carbon steel. Results in the presence of
bacteria display the formation of black corrosion products allegedly FeS and a
sudden increase (more than 400mV) of the corrosion potential of electrode
immersed in artificial seawater or in field water (produced water mixed with
aquifer seawater). Impedance tests provided information about the mechanisms of
the interface carbon steel/bacteria depending on the medium used: mass transfer
limitation in artificial seawater was observed whereas that in field water was
only charge transfer phenomenon. Denaturing Gradient Gel Electrophoresis (DGGE)
results proved that bacterial diversity decreased when cultivating the debris in
the media used and suggested that the bacteria involved in the whole set of
results are mainly sulphate reducing bacteria (SRB) and some other bacteria that
make part of the taxonomic order Clostridiales.
PMID- 24355514
TI - Ketoacidosis at diagnosis of type 1 diabetes in children and adolescents:
frequency and clinical characteristics.
AB - BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening acute
complication of type 1 diabetes mellitus (T1DM). Although the frequency of DKA as
first manifestation of T1DM is higher in developing compared developed countries,
there is paucity of information on its characteristics in developing countries.
METHODS: This retrospective study determined the frequency of ketoacidosis at
diagnosis of new-onset type 1 diabetes and described the clinical characteristics
of the patients seen between 1996 and 2011 by auditing the hospital records of
all cases. The diagnosis of diabetic ketoacidosis (DKA) was based on the presence
of hyperglycaemia (blood glucose > 11 mmol/L), acidosis (serum bicarbonate < 15
mmol/L) and ketonuria (urine ketone >=1+). RESULTS: At diagnosis of new-onset
type 1 diabetes mellitus, three-quarter (77.1%) of the children and adolescents
presented with DKA. Comparing the frequency of DKA during the initial 8 years
(1996-2003) with the later 8 years (2004-2011), it was 81.8% vs 73.1%; p > 005.
The frequency has not shown any significant declined over a 16-year period. The
frequency of re-admission in ketoacidosis was 24.3%. CONCLUSION: Three-quarter of
children and adolescents present with DKA as first manifestation of T1DM with no
significant decline in frequency over a 16-year period in our hospital.
PMID- 24355515
TI - Nonhomeomorphic topological transformations and the challenge of collision
detection in virtual reality simulation in neurosurgery.
PMID- 24355516
TI - Inflammation, macrophages, and targeted imaging in intracranial aneurysms.
PMID- 24355518
TI - Concussion: neurosurgery's mission in social awareness.
PMID- 24355517
TI - Proximal versus distal protection during carotid artery stenting: analysis of the
two treatment approaches and associated clinical outcomes.
AB - OBJECTIVE: Cerebral protection device utilization during carotid artery stenting
(CAS) has been shown to decrease risk of perioperative stroke. The two most
commonly used devices are distal filters and proximal protection devices, which
allow blood flow cessation or flow reversal. The goal of the present study was to
examine anatomic and morphologic characteristics of the treated lesions using
each type of cerebral protection device and compare clinical 30-day adverse event
rates between the two cerebral protection groups. METHODS: We conducted a single
center, retrospective review of consecutive CAS cases with proximal protection
devices that were matched with CAS cases using distal filter protection devices
based on indication (symptomatic vs. asymptomatic), age, and gender. We reviewed
clinical, anatomic, and morphologic characteristics of the stented lesions in
cases of proximal or distal protection and also studied the rate of major adverse
events within the first 30 days after the procedure. RESULTS: We identified a
total of 70 patients treated with proximal protection devices who were matched in
a blinded fashion to 70 cases with distal protection. There was a significantly
higher number of high-risk lesions in patients who had CAS using proximal
protection devices (P = 0.009). There was no significant difference in overall
frequency of 30-day adverse outcomes (transient ischemic
attack/stroke/reperfusion hemorrhage/death) between the two groups (P = 1.0).
CONCLUSIONS: Our study is the first attempt (to our knowledge) to review and
compare anatomic and morphologic characteristics of the stented lesions in cases
of proximal versus distal protection for CAS. Our data indicate that in properly
selected patients both approaches could be equally safe and effective.
PMID- 24355519
TI - Arterial recanalization benefits even neurologically improving stroke patients
after intravenous tissue-type plasminogen activator.
PMID- 24355520
TI - Therapeutic potential of anti-IL-1beta IgY in guinea pigs with allergic asthma
induced by ovalbumin.
AB - BACKGROUND: Interleukin-1 beta (IL-1beta) plays pivotal roles in the progression
of allergic airway inflammation. This study aims to determine whether the
blockade of IL-1beta can inhibit airway inflammation in guinea pigs with allergic
asthma induced by the inhalation of aerosolized ovalbumin (OVA). METHODS: Healthy
guinea pigs treated with saline were used as normal controls (group C). The
guinea pigs with allergic asthma induced by the inhalation of aerosolized OVA
were randomly divided into three groups: (1) the M group containing negative
control animals treated with saline; (2) the Z1 group containing animals treated
by the inhalation of atomized 0.1% anti-IL-1beta immunoglobulin yolk (IgY); and
(3) the Z2 group containing positive control animals that were treated with
budesonide. The inflammatory cells in the peripheral blood (PB) and
bronchoalveolar lavage fluid (BALF) were evaluated using methylene blue and eosin
staining. Cytokine concentrations were measured using an enzyme-linked
immunosorbent assay. Pulmonary sections were examined using hematoxylin-eosin
staining. RESULTS: Allergic inflammation and damage to the pulmonary tissues were
decreased in the Z1 group compared to the M group. Eosinophils and neutrophils in
the PB and BALF were significantly decreased in the Z1 group compared to the M
group (P<0.05). Treatment with anti-IL-1beta IgY significantly reduced the levels
of IL-1beta, IL-4, IL-8, IL-13, TNF-alpha, TGF-beta1 and IgE in the BALF
(P<0.05). CONCLUSION: The inhalation of aerosolized anti-IL-1beta IgY inhibits
pathological responses in the pulmonary tissues of guinea pigs with allergic
asthma. The inhibitory activity may be due to the decrease in the numbers of
eosinophils and neutrophils and the reduced levels of inflammatory cytokines and
IgE in the PB and BALF.
PMID- 24355521
TI - Symptom distress predicts long-term health and well-being in allogeneic stem cell
transplantation survivors.
AB - The number of survivors after allogeneic hematopoietic stem cell transplantation
(HSCT) continues to increase, yet their survivorship experience has not been
fully characterized. This study examines the health status and health-related
quality of life (HRQL) of HSCT survivors. The aims of the study were to: (1)
explore the baseline and change over time in these health outcomes, and (2)
characterize subgroups experiencing adverse outcomes. In this longitudinal study,
adults who survived >3 years from date of allogeneic HSCT completed a series of
patient-reported outcome measures annually, including measures of health status,
HRQL, and symptoms. Data were analyzed using hierarchical linear modeling.
Subjects (N = 171) were on average 44 (+/-13.5) years of age and primarily male
(62.6%); 40% were Hispanic. Mean scores for physical and mental health and HRQL
were preserved relative to population norms. Hierarchical linear modeling
revealed no significant change in the mean trajectories of these outcomes,
although significant between-individual variability was observed. When
controlling for demographic and clinical factors, physical symptom distress
negatively affected all outcomes. The impact of symptom distress on physical
health varied based on time since HSCT; impairment in physical health was
greatest in survivors experiencing high symptom distress and who were within the
first decade post transplantation. Extended treatment with systemic
immunosuppressive therapy also predicted inferior physical health. These findings
suggest that patient-centered outcomes are preserved relative to normative values
and are generally stable after allogeneic HSCT, although survivors with
persistent symptoms and those receiving systemic immunosuppression experience
impairments in health status and HRQL.
PMID- 24355522
TI - Performance of a new rapid test for the detection of hepatitis B surface antigen
in various patient populations.
AB - BACKGROUND: Rapid diagnostic tests (RDT) have been developed for the detection of
hepatitis B surface antigen (HBsAg). They represent a promising alternative to
enzyme immunoassays and a powerful tool for large-scale screening and diagnosis
of HBV infection, especially in regions without easy access to serological and
molecular testing. OBJECTIVES: The aims of the present study were to evaluate the
characteristics and clinical performance of a new CE-marked HBsAg RDT, DRW-HBsAg
v2.0 assay (Diagnostics for the Real WorldTM, Ltd., USA), in various patient
populations, including those chronically infected with HBV, patients with severe
acute hepatitis of unknown origin and pregnant women with unknown HBV serological
status at delivery. RESULTS: The lower limit of detection of the assay, evaluated
in 21 clinical samples, ranged from 0.30 +/- 0.07 to 0.97 +/- 0.26 international
units/mL (using Abbott Architect as a reference), depending on the HBV genotype.
The assay tested positive in 100% of patients with chronic hepatitis B, 96.3% of
HBsAg-positive acute hepatitis patients, and 95.2% of HBsAg-positive pregnant
women. Its specificity was 98.8% in HBsAg-negative patients, 98.7% in HBsAg
negative patients with acute hepatitis of unknown origin and 97.8% in HBsAg
negative pregnant women. Amino acid substitutions in the HBsAg major hydrophilic
region did not affect HBsAg detection by DRW-HBsAg v2.0. CONCLUSIONS: The new DRW
HBsAg v2.0 assay is a simple, rapid, easy-to-run and highly sensitive assay that
can be used in both high- and low-risk populations for the diagnosis of HBsAg
carriage. It appears to be a promising new tool for large-scale screening and
diagnosis of HBV infection.
PMID- 24355524
TI - Stathmin 1 is involved in the highly proliferative phenotype of high-risk
myelodysplastic syndromes and acute leukemia cells.
AB - Stathmin 1 is an important cytoplasmic microtubule-destabilizing protein that
plays critical roles in proliferation and accurate chromosome segregation through
regulation of microtubule dynamics. High levels of Stathmin 1 expression have
been reported in leukemia and solid tumors. However, Stathmin 1 has not been
studied in myelodysplastic syndrome cells. We, herein, report that significantly
higher Stathmin 1 levels were observed in proliferating hematopoietic cells, in
high-risk MDS and acute leukemia cells. In addition, Stathmin 1 silencing in U937
and Namalwa leukemia cells reduced cell proliferation and clonogenicity. Our data
suggest that Stathmin 1 expression may be related to the highly proliferative
phenotype of hematopoietic cells and add new insights into the participation of
Stathmin 1 in hematological malignancies.
PMID- 24355525
TI - Social interactions and their connection to aggression and ovarian development in
orphaned worker bumblebees (Bombus impatiens).
AB - This study examines the social dynamics of reproductive conflict. Orphaned worker
bumblebees (Bombus impatiens) with comparatively high or low levels of social
activity were paired to determine whether aggression and reproduction could be
traced to earlier social interactions. The workers were paired according to their
levels of social activity (a socially active+another socially active worker,
socially active+socially inactive, and two socially inactive workers). The
presence or absence of brood was also manipulated. The absence of brood increased
both aggression and ovarian development, suggesting that aggression and
reproduction are associated or that there is a third variable that affects both.
Socially active pairs were significantly more aggressive: here, social activity
can be taken as an early indicator of aggression. No such effect, however, was
obtained on ovarian development as the socially active pairs did not differ on
their degree of ovarian development compared to the others. Within the socially
active+socially inactive pairs, the socially active worker did not have more
developed ovaries and was not more aggressive than her socially inactive partner.
Results highlight that environmental conditions (the absence of brood) can
predict ovarian development and although social activity can be observed prior to
aggression, differences in aggression do not translate into differences in
ovarian development under these conditions.
PMID- 24355526
TI - C9ORF72 repeat expansion not detected in patients with multiple sclerosis.
AB - A hexanucleotide repeat expansion in the chromosome 9 Open Reading Frame 72 gene
(C9ORF72) has recently been reported to be cause of familial amyotrophic lateral
sclerosis and frontotemporal lobar degeneration. Nevertheless, in the last few
years this mutation has been found to be associated with heterogeneous
phenotypes, including multiple sclerosis (MS) in concurrence with amyotrophic
lateral sclerosis. In this study, we sought to evaluate the presence of the
C9ORF72 repeat expansion in a cohort consisting of 314 patients with MS and 222
control subjects. No pathogenic expansion was found in MS and control
populations, suggesting that C9ORF72 does not play a major role in MS
pathogenesis.
PMID- 24355527
TI - Comparative study of Parkinson's disease and leucine-rich repeat kinase 2
p.G2019S parkinsonism.
AB - Parkinson disease is a progressive neurodegenerative disease for which leucine
rich repeat kinase 2 (LRRK2 carriers) p.G2019S confers substantial genotypic and
population attributable risk. With informed consent, we have recruited clinical
data from 778 patients from Tunisia (of which 266 have LRRK2 parkinsonism) and
580 unaffected subjects. Motor, autonomic, and cognitive assessments in
idiopathic Parkinson disease and LRRK2 patients were compared with regression
models. The age-associated cumulative incidence of LRRK2 parkinsonism was also
estimated using case-control and family-based designs. LRRK2 parkinsonism
patients had slightly less gastrointestinal dysfunction and rapid eye movement
sleep disorder. Overall, disease penetrance in LRRK2 carriers was 80% by 70 years
but women become affected a median 5 years younger than men. Idiopathic Parkinson
disease patients with younger age at diagnosis have slower disease progression.
However, age at diagnoses does not predict progression in LRRK2 parkinsonism.
LRRK2 p.G2019S mutation is a useful aid to diagnosis and modifiers of disease in
LRRK2 parkinsonism may aid in developing therapeutic targets.
PMID- 24355528
TI - Health-related quality of life and metabolic risk in patients with psychosis.
AB - Improved Health-related quality of life (HRQoL) is an alternative treatment goal
for individuals with psychosis, who have up to two times greater prevalence of
type 2 diabetes, hypertension and obesity than the general population. AIM: to
compare HRQoL in patients with psychosis, especially schizophrenia, with a
reference sample and explore the relationship between HRQoL and metabolic risk
factors in these patients. METHODS: a prospective cohort study was carried out in
specialized psychiatric outpatient departments in Sweden. The patients were
invited consecutively. A prospective population-based study of public health in
the south-east of Sweden served as reference group. Patients were assessed with
psychiatric questionnaires that included Global Assessment of Functioning (GAF).
Health-related quality of life was assessed using the questionnaire EQ5D, both
for patients and the population, and several other health status outcomes were
used. RESULTS: At 73%, schizophrenia and schizoaffective disorder were the most
common diagnoses in the patient group. The results in patients (n=903) and
population (n=7238) showed significant differences in lower EQ5D among patients.
According to the definition by the International Diabetes Federation (IDF),
elevated blood pressure was the only metabolic risk associated with lower HRQoL
in patients. Raised LDL-cholesterol levels were also significantly related to
lower HRQoL. CONCLUSION: patients suffering from psychosis had significantly
lower HRQoL regarding all components in EQ5D, except for the pain/discomfort
component. Almost half of the patient group met the criteria for metabolic
syndrome. According to the IDF criteria, elevated blood pressure was the only
metabolic risk factor that had an impact on HRQoL.
PMID- 24355529
TI - Relationship between cognition, clinical and cognitive insight in psychotic
disorders: a review and meta-analysis.
AB - The neurocognitive theory of insight posits that poor insight in psychotic
illnesses is related to cognitive deficits in cognitive self-appraisal
mechanisms. In this paper we perform a comprehensive meta-analysis examining
relationships between clinical insight and neurocognition in psychotic disorders.
We have also completed a meta-analysis of studies examining 'cognitive insight',
as measured by the Beck Cognitive Insight Scale (BCIS), and its relationship with
neurocognitive function in patients with psychosis. The clinical insight analysis
included data from 72 studies and a total population of 5429 patients. We found
that insight in psychosis was significantly associated with total cognition
(r=0.16, p<0.001), IQ (r=0.16, p<0.001), memory (r=0.13, p<0.001) and executive
function (r=0.14, p<0.001). All of these correlations were stronger when examined
in patients with schizophrenia only. In the BCIS analysis we included 7 studies
and 466 patients in total. We found that no significant associations were found
between the self-reflectiveness sub-component and neurocognition. By contrast
there were significant correlations between the self-certainty subcomponent and
memory (r=-0.23, p<0.001), IQ (r=-0.19, p<0.001) and total cognition (r=-0.14,
p=0.01). We did not find evidence of significant publication bias in any
analyses. Overall, our results indicate that there is a small but significant
relationship between clinical insight, some aspects of cognitive insight and
neurocognition. These findings reflect the complexity of the insight construct
and indicate that while the neurocognitive model is important it is likely to be
one of many which contribute to the understanding of this phenomenon.
PMID- 24355523
TI - Disruption of fetal hormonal programming (prenatal stress) implicates shared risk
for sex differences in depression and cardiovascular disease.
AB - Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD)
represents the fourth leading cause of morbidity and mortality worldwide, and
women have a two times greater risk than men. Thus understanding the
pathophysiology has widespread implications for attenuation and prevention of
disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from
alterations in fetal programming consequent to the prenatal maternal environments
that produce excess glucocorticoids, which then drive sex-dependent developmental
alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry
impacting mood, stress regulation, autonomic nervous system (ANS), and the
vasculature in adulthood. Evidence is consistent with the hypothesis that
disruptions of pathways associated with gamma aminobutyric acid (GABA) in
neuronal and vascular development and growth factors have critical roles in key
developmental periods and adult responses to injury in heart and brain.
Understanding the potential fetal origins of these sex differences will
contribute to development of novel sex-dependent therapeutics.
PMID- 24355530
TI - Further evidence for genetic association of CACNA1C and schizophrenia: new risk
loci in a Han Chinese population and a meta-analysis.
AB - CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia
by several replicated genome wide association studies. While these results have
been consistent among studies in European populations, the findings in East Asian
populations have varied. To test whether CACNA1C is a risk gene for
schizophrenia, we conducted a case-control study in 5897 schizophrenic patients
and 6323 healthy control subjects selected from Han Chinese population. Our study
replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI:
1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a
novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta
analysis of rs1006737 combining our study and previous studies was conducted in a
total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta
analysis, the association between rs1006737 and schizophrenia remained
significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no
heterogeneity between East Asian and European ancestries (chi(2)[1]=0.07,
P=0.795), and the difference in pooled ORs between ancestries was not significant
(Z=0.25, P=0.801). Our results provide further support for associations of
rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044
in a Han Chinese population, and further establish CACNA1C as an important
susceptibility gene for the disease across world populations.
PMID- 24355531
TI - Genomic characteristics of a novel reovirus from Muscovy duckling in China.
AB - A new reovirus was isolated from a sick Muscovy duckling with hemorrhagic
necrotic lesions in the liver in Zhejiang, China in 2000 and was tentatively
denoted a new type of Muscovy duck reovirus (N-MDRV ZJ00M). This reovirus was
propagated in a chicken fibroblast cell line (DF-1) with obvious cytopathic
effects. The reovirus's genome was 23,419 bp in length with an approximately 50%
G+C content and 10 dsRNA segments encoding 12 proteins. The length of the genomic
segments was similar to those of avian reoviruses (ARVs), which range from 3959
nt (L1) to 1191 nt (S4) in size. All of the segments have the conserved terminal
sequences 5'-GCUUUUU...UUCAUC-3', and all of the genome segments, with the
exception of S1, apparently encoded one single primary translation product. The
genome analysis revealed that the S1 segment of N-MDRV is a tricistronic gene
that encodes the overlapping ORFs for p10, p18, and sigmaC. This finding is
similar to that found for ARVs but distinct from that found for classical MDRV
and GRV, which have a bicistronic S4 segment that encodes p10 and sigmaC and do
not encode p18. The amino acid (aa) alignments of the putative proteins encoded
by the main ORF in each segment revealed a high similarity (14.1-100%) to the
counterpart proteins encoded by other ARV species from the avian orthoreoviruses
(e.g., ARV, classical MDRV and N-MDRV) in the Orthoreovirus genus, particularly
with N-MDRV (94.6-100%). The phylogenetic analysis of the nucleotide sequences of
all 10 genome segments revealed that N-MDRV ZJ00M is distinct from all other
described reovirus species groups but is a separated from the ARV (including MDRV
and GRV) species within orthoreovirus species group II and grouped into the
classical MDRV and GRV genogroup with the N-MDRV isolates. The MDRV genogroup can
be further divided into two genotype clusters. The morphological and pathological
analyses and the genetic characterization of N-MDRV ZJ00M suggest that it belongs
to genotype 2 (N-MDRV). In addition, the RT-PCR assays of DRV diseased duckling
and gosling samples collected from different regions of China during 2000-2013
indicate that N-MDRV is currently the prevalent genotype in China.
PMID- 24355532
TI - Virulence determinants of Salmonella Gallinarum biovar Pullorum identified by PCR
signature-tagged mutagenesis and the spiC mutant as a candidate live attenuated
vaccine.
AB - Salmonella Gallinarum biovar Pullorum (S. Gallinarum biovar Pullorum) is the
causative agent of pullorum disease (PD) in chickens which results in
considerable economic losses to the poultry industries in developing countries.
PCR-Signature Tagged Mutagenesis was used to identify virulence determinants of
S. Gallinarum biovar Pullorum and novel attenuated live vaccine candidates for
use against this disease. A library of 1800 signature-tagged S. Gallinarum biovar
Pullorum mutants was constructed and screened for virulence-associated genes in
chickens. The attenuation of 10 mutants was confirmed by in vivo and in vitro
competitive index (CI) studies. The transposons were found to be located in SPI-1
(2/10 mutants), SPI-2 (3/10), the virulence plasmid (1/10) and non-SPI genes
(4/10). One highly attenuated spiC mutant persisted in spleen and liver for less
than 10 days and induced high levels of circulating antibody and protective
immunity against oral challenge in young broiler chickens. The spiC mutant is a
potential new vaccine candidate for use with chickens against this disease.
PMID- 24355533
TI - Illumina sequencing of the V4 hypervariable region 16S rRNA gene reveals
extensive changes in bacterial communities in the cecum following carbohydrate
oral infusion and development of early-stage acute laminitis in the horse.
AB - In the equine carbohydrate overload model of acute laminitis, disease progression
is associated with changes in bacteria found in the cecum. To date, research has
focused on changes in specific Gram-positive bacteria in this portion of the
intestinal tract. Metagenomic methods are now available making it possible to
interrogate microbial communities using animal protocols that sufficiently power
a study. In this study, the microbiota in cecal fluid collected from control, non
laminitic horses (n=8) and from horses with early-stage acute laminitis induced
with either oligofructan (n=6) or cornstarch (n=6) were profiled. The microbiota
were identified based on sequencing the V4 hypervariable region of the 16S rRNA
gene. The results of the study show that the relative abundance of Lactobacillus
sp. and Streptococcus sp. increased significantly (p<0.05) following OF and CS
infusion. Other significant changes included an increase (p<0.05) in relative
abundance of Veillonella sp. and Serratia sp., two potentially pathogenic, Gram
negative bacteria. Significant decreases in the relative abundance of presumptive
normal flora were detected as well. Although changes in cecal microbiota
described in this communication are from a pilot study, it is hypothesized that
an overgrowth of pathogenic Gram-negative bacteria develops and contributes to
enterocolitis, pyrexia and lameness in the carbohydrate overload model of acute
laminitis.
PMID- 24355534
TI - Brachyspira and its role in avian intestinal spirochaetosis.
AB - The fastidious, anaerobic spirochaete Brachyspira is capable of causing enteric
disease in avian, porcine and human hosts, amongst others, with a potential for
zoonotic transmission. Avian intestinal spirochaetosis (AIS), the resulting
disease from colonisation of the caeca and colon of poultry by Brachyspira leads
to production losses, with an estimated annual cost of circa L 18 million to the
commercial layer industry in the United Kingdom. Of seven known and several
proposed species of Brachyspira, three are currently considered pathogenic to
poultry; B. alvinipulli, B. intermedia and B. pilosicoli. Currently, AIS is
primarily prevented by strict biosecurity controls and is treated using
antimicrobials, including tiamulin. Other treatment strategies have been
explored, including vaccination and probiotics, but such developments have been
hindered by a limited understanding of the pathobiology of Brachyspira. A lack of
knowledge of the metabolic capabilities and little genomic information for
Brachyspira has resulted in a limited understanding of the pathobiology. In
addition to an emergence of antibiotic resistance amongst Brachyspira, bans on
the prophylactic use of antimicrobials in livestock are driving an urgent
requirement for alternative treatment strategies for Brachyspira-related
diseases, such as AIS. Advances in the molecular biology and genomics of
Brachyspira heralds the potential for the development of tools for genetic
manipulation to gain an improved understanding of the pathogenesis of
Brachyspira.
PMID- 24355535
TI - Butcherbird polyomavirus isolated from a grey butcherbird (Cracticus torquatus)
in Queensland, Australia.
AB - A novel avian polyomavirus was detected in peri-ocular skin lesions collected
from a grey butcherbird (Cracticus torquatus), using a combination of multiply
primed rolling circle amplification, nested PCR and long range PCR. The sequence
of Butcherbird polyomavirus was determined by combining next generation
sequencing and primer walking techniques. The circular double-stranded DNA genome
of Butcherbird polyomavirus consisted of 5084 bp, and encoded six open reading
frames (ORF-X, VP2, VP3, VP1, small T-antigen and large T-antigen). Phylogenetic
analysis placed it amongst other members of the genus Avipolyomavirus, most
closely related to Crow polyomavirus. Next generation sequencing enabled the
detection of DNA fragments similar to, but distinct from, Canarypox virus within
the same lesion from which Butcherbird polyomavirus was amplified, thus
confirming an avipolyomavirus-avipoxvirus co-infection in the peri-ocular skin
lesions of this grey butcherbird.
PMID- 24355536
TI - Poultry as a possible source of non-typhoidal Salmonella enterica serovars in
humans in Bangladesh.
AB - We investigated Salmonella enterica isolates from human clinical cases of
gastroenteritis to determine the distribution of non-typhoidal Salmonella
serovars in the human population, and compared them to isolates originating from
poultry by serotyping, phage typing, plasmid profiling, pulsed-field gel
electrophoresis (PFGE) and multi-locus sequence typing (MLST) to evaluate the
potential role of poultry in human non-typhoidal salmonellosis in Bangladesh.
Nine different serovars were identified among the human isolates of which
Salmonella Paratyphi B var Java (S. Java), S. Kentucky, S. Enteritidis, S.
Virchow and S. Weltevreden also were commonly isolated from poultry. The poultry
isolates belonging to S. Java, S. Kentucky and S. Enteritidis were
indistinguishable from human isolates or genetically closely related, based on
PFGE profiles and MLST. S. Kentucky clone ST198 and S. Java clone ST43 both well
known cause of human infections were also isolated from poultry.
PMID- 24355537
TI - Dietary fibre intake and risk of cardiovascular disease: systematic review and
meta-analysis.
AB - OBJECTIVE: To investigate dietary fibre intake and any potential dose-response
association with coronary heart disease and cardiovascular disease. DESIGN:
Systematic review of available literature and dose-response meta-analysis of
cohort studies using random effects models. DATA SOURCES: The Cochrane Library,
Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS,
and hand searching. ELIGIBILITY CRITERIA FOR STUDIES: Prospective studies
reporting associations between fibre intake and coronary heart disease or
cardiovascular disease, with a minimum follow-up of three years and published in
English between 1 January 1990 and 6 August 2013. RESULTS: 22 cohort study
publications met inclusion criteria and reported total dietary fibre intake,
fibre subtypes, or fibre from food sources and primary events of cardiovascular
disease or coronary heart disease. Total dietary fibre intake was inversely
associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95%
confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to
0.94)). There was evidence of some heterogeneity between pooled studies for
cardiovascular disease (I(2)=45% (0% to 74%)) and coronary heart disease
(I(2)=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable
sources were inversely associated with risk of coronary heart disease and
cardiovascular disease. Fruit fibre intake was inversely associated with risk of
cardiovascular disease. CONCLUSIONS: Greater dietary fibre intake is associated
with a lower risk of both cardiovascular disease and coronary heart disease.
Findings are aligned with general recommendations to increase fibre intake. The
differing strengths of association by fibre type or source highlight the need for
a better understanding of the mode of action of fibre components.
PMID- 24355538
TI - Primary hip replacement prostheses and their evidence base: systematic review of
literature.
AB - OBJECTIVE: To determine the extent to which prostheses with no readily available
evidence to support their use are being implanted in primary total hip
arthroplasty. DESIGN: Systematic review of the literature. DATA SOURCES: The 9th
annual report of the National Joint Registry of England and Wales (NJR) was
analysed to identify prostheses with an Orthopaedic Data Evaluation Panel rating
of "unclassified" or "pre-entry" used in primary total hip arthroplasty in 2011.
A systematic review of those prostheses was carried out using PubMed, Cochrane,
Embase, OVID, and Google databases. STUDY SELECTION: Prostheses used in primary
total hip arthroplasty as published in the NJR's 9th annual report were analysed.
Only literature that included the name of the prosthesis was included. Literature
yielded in the search results was excluded if it reported animal, non
orthopaedic, non-total hip arthroplasty, or non-device related studies. RESULTS:
The systematic review found that 24% (57/235) of all hip replacement implants
available to surgeons in the UK have no evidence for their clinical
effectiveness. It also shows that 10,617 (7.8%) of the 136,593 components used in
primary hip replacements in 2011 were implanted without readily identifiable
evidence of clinical effectiveness. These comprised 157 cemented stems (0.5% of
34,655 implanted), 936 (2.8% of 33,367) uncemented stems, 1732 (7.1% of 24,349)
cemented cups, and 7577 (17.1% of 44,222) uncemented cups. CONCLUSIONS: This
study shows that a considerable proportion of prostheses available to orthopaedic
surgeons have no readily available evidence of clinical effectiveness to support
their use. Concern exists about the current system of device regulation, and the
need for a revised process for introducing new orthopaedic devices is
highlighted.
PMID- 24355539
TI - Hospital food can be improved only by legislation.
PMID- 24355540
TI - Eat more fibre.
PMID- 24355541
TI - New and unproved medical devices.
PMID- 24355543
TI - Bronchopleural fistula and the role of contemporary imaging.
AB - One of the most morbid postoperative complications after a lobectomy or a
pneumonectomy is a bronchopleural fistula (BPF). The diagnosis and identification
of BPF may be challenging, often requiring repeat imaging and invasive tests,
including bronchoscopy, thoracoscopic exploration, or even open exploration. The
purpose of this article is to review the types and presentations of BPF and to
describe the role of noninvasive imaging for diagnosis and surgical treatment
planning. We focused on multidetector computed tomography and advanced
postprocessing applications such as multiplanar reconstructions, virtual
bronchoscopy, and volume rendering images, including minimum-intensity and
maximum-intensity projections. Both multidetector computed tomography and nuclear
scintigraphy are reliable noninvasive imaging modalities that can be used
expeditiously in an outpatient setting and may prove to be a more cost-effective
strategy to identify the fistula as well as conduct postoperative surveillance.
These modalities can be used for accurate and efficient testing for earlier
diagnosis and treatment planning, thereby significantly improving patient
outcome. Additional advanced postprocessing techniques using already acquired
imaging data can provide complementary information that is both visually
accessible and anatomically meaningful for the surgeon. Better understanding of
the potential uses and benefits of these techniques will eventually improve the
diagnostic accuracy, optimize preoperative planning, and facilitate follow-up for
patients with BPF with improved patient outcomes.
PMID- 24355542
TI - Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in
human lung cancer cells from the NCI-60 panel.
AB - Tyrosyl-DNA-phosphodiesterase 1 (TDP1) repairs 3'-blocking DNA lesions by
catalytically hydrolyzing the tyrosyl-DNA-phosphodiester bond of trapped
topoisomerase I (Top1) cleavage complexes (Top1cc). It also removes 3'-blocking
residues derived from oxidative damage or incorporation of chain terminating
anticancer and antiviral nucleosides. Thus, TDP1 is regarded as a determinant of
resistance to Top1 inhibitors and chain terminating nucleosides, and possibly of
genomic stability. In the 60 cell lines of the NCI Developmental Therapeutic
Anticancer Screen (the NCI-60), whose whole genome transcriptome and mutations
have recently been characterized, we discovered two human lung cancer cell lines
deficient for TDP1 (NCI_H522 and HOP_62). HOP_62 shows undetectable TDP1 mRNA and
NCI_H522 bears a homozygous deleterious mutation of TDP1 at a highly conserved
amino acid residue (K292E). Absence of TDP1 protein and lack of TDP1 catalytic
activity were demonstrated in cell lysates from both cell lines. Lack of TDP1
expression in HOP_62 was shown to be due to TDP1 promoter hypermethylation. Our
study provides insights into the possible inactivation of TDP1 in cancers and its
relationship to cellular response to Top1-targeted drugs. It also reveals two
TDP1 knockout lung cancer cell lines for further TDP1 functional analyses.
PMID- 24355544
TI - Diagnostic value of three-dimensional magnetic resonance imaging of inner ear
after intratympanic gadolinium injection, and clinical application of magnetic
resonance imaging scoring system in patients with delayed endolymphatic hydrops.
AB - OBJECTIVE: Three-dimensional fluid-attenuated inversion recovery magnetic
resonance imaging of the inner ear after intratympanic injection of gadolinium,
together with magnetic resonance imaging scoring of the perilymphatic space, were
used to investigate the positive identification rate of hydrops and determine the
technique's diagnostic value for delayed endolymphatic hydrops. METHODS: Twenty
five patients with delayed endolymphatic hydrops underwent pure tone audiometry,
bithermal caloric testing, vestibular-evoked myogenic potential testing and three
dimensional magnetic resonance imaging of the inner ear after bilateral
intratympanic injection of gadolinium. The perilymphatic space of the scanned
images was analysed to investigate the positive identification rate of
endolymphatic hydrops. RESULTS: According to the magnetic resonance imaging
scoring of the perilymphatic space and the diagnostic standard, 84 per cent of
the patients examined had endolymphatic hydrops. In comparison, the positive
identification rates for vestibular-evoked myogenic potential and bithermal
caloric testing were 52 per cent and 72 per cent respectively. CONCLUSION: Three
dimensional magnetic resonance imaging after intratympanic injection of
gadolinium is valuable in the diagnosis of delayed endolymphatic hydrops and its
classification. The perilymphatic space scoring system improved the diagnostic
accuracy of magnetic resonance imaging.
PMID- 24355546
TI - Neuroscience, quantum indeterminism and the Cartesian soul.
AB - Quantum indeterminism is frequently invoked as a solution to the problem of how a
disembodied soul might interact with the brain (as Descartes proposed), and is
sometimes invoked in theories of libertarian free will even when they do not
involve dualistic assumptions. Taking as example the Eccles-Beck model of
interaction between self (or soul) and brain at the level of synaptic exocytosis,
I here evaluate the plausibility of these approaches. I conclude that
Heisenbergian uncertainty is too small to affect synaptic function, and that
amplification by chaos or by other means does not provide a solution to this
problem. Furthermore, even if Heisenbergian effects did modify brain functioning,
the changes would be swamped by those due to thermal noise. Cells and neural
circuits have powerful noise-resistance mechanisms, that are adequate protection
against thermal noise and must therefore be more than sufficient to buffer
against Heisenbergian effects. Other forms of quantum indeterminism must be
considered, because these can be much greater than Heisenbergian uncertainty, but
these have not so far been shown to play a role in the brain.
PMID- 24355545
TI - Left-hemisphere activation is associated with enhanced vocal pitch error
detection in musicians with absolute pitch.
AB - The ability to process auditory feedback for vocal pitch control is crucial
during speaking and singing. Previous studies have suggested that musicians with
absolute pitch (AP) develop specialized left-hemisphere mechanisms for pitch
processing. The present study adopted an auditory feedback pitch perturbation
paradigm combined with ERP recordings to test the hypothesis whether the neural
mechanisms of the left-hemisphere enhance vocal pitch error detection and control
in AP musicians compared with relative pitch (RP) musicians and non-musicians
(NM). Results showed a stronger N1 response to pitch-shifted voice feedback in
the right-hemisphere for both AP and RP musicians compared with the NM group.
However, the left-hemisphere P2 component activation was greater in AP and RP
musicians compared with NMs and also for the AP compared with RP musicians. The
NM group was slower in generating compensatory vocal reactions to feedback pitch
perturbation compared with musicians, and they failed to re-adjust their vocal
pitch after the feedback perturbation was removed. These findings suggest that in
the earlier stages of cortical neural processing, the right hemisphere is more
active in musicians for detecting pitch changes in voice feedback. In the later
stages, the left-hemisphere is more active during the processing of auditory
feedback for vocal motor control and seems to involve specialized mechanisms that
facilitate pitch processing in the AP compared with RP musicians. These findings
indicate that the left hemisphere mechanisms of AP ability are associated with
improved auditory feedback pitch processing during vocal pitch control in tasks
such as speaking or singing.
PMID- 24355547
TI - Long-term intrathecal baclofen: outcomes after more than 10 years of treatment.
AB - OBJECTIVE: To report outcomes of intrathecal baclofen (ITB) therapy for
spasticity management in a cohort of patients who had received this treatment for
at least 10 years. DESIGN: A cross-sectional survey and retrospective chart
review. SETTING: An academic rehabilitation outpatient clinic. PARTICIPANTS:
Adult patients with spasticity treated with ITB for at least 10 years. MAIN
OUTCOME MEASUREMENTS: Surveys included the Brief Pain Inventory, Penn Spasm
Frequency Scale, Epworth Sleepiness Scale, Fatigue Severity Scale, Diener
Satisfaction with Life, Life Satisfaction Questionnaire, and Intrathecal Baclofen
Survey. RESULTS: Twenty-four subjects completed the surveys. The subjects had
been treated with ITB from 10.0-28.4 years, with a mean (standard deviation) of
14.7 +/- 4.2 years. The mean (standard deviation) dose of ITB was 627.9 +/- 306.7
MUg/d, with only 6 subjects averaging daily dose changes of more than 10%
compared with 3 years earlier. The mean (standard deviation) scores on outcomes
surveys were the following: 2.6 +/- 2.3 for pain severity on the Brief Pain
Inventory, 1.4 +/- 0.7 for spasm severity on the Penn Spasm Frequency Scale, 7.9
+/- 5.4 on the Epworth Sleepiness Scale, 4.1 +/- 1.6 on the Fatigue Severity
Scale, 19.4 +/- 8.1 on the Diener Satisfaction with Life, 3.9 +/- 0.9 on the Life
Satisfaction Questionnaire, and 8.8 +/- 1.9 for overall satisfaction with ITB on
the Intrathecal Baclofen Survey. On the Brief Pain Inventory, the mean scores for
pain severity and interference of pain with life showed moderate inverse
correlations with ITB dose (r = -0.386, P = .115; and r = -0.447, P = .062,
respectively). On the Life Satisfaction Questionnaire, the mean scores for life
satisfaction showed statistically significant positive correlation with ITB dose
(r = 0.549, P = .021). CONCLUSIONS: The subjects reported low levels of pain,
moderate levels of life satisfaction, normal levels of sleepiness, low-to
moderate levels of fatigue, infrequent spasms at mild-to-moderate severity, and
high levels of satisfaction. The efficacy and favorable adverse effect profile of
ITB therapy was sustained in this cohort of subjects with more than a decade of
treatment.
PMID- 24355548
TI - An observational 7-year study of continuous subcutaneous insulin infusion for the
treatment of type 1 diabetes mellitus.
AB - This work reports the experience with use of continuous subcutaneous insulin
infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and
previously treated with multiple daily insulin injections (MDII). MATERIAL AND
METHODS: A retrospective, observational study in 112 patients with diabetes
mellitus treated with CSII from 2005 to 2012, previously treated with MDII and
receiving individualized diabetic education with a specific protocol. Variables
analyzed included: prevalence of the different indications of pump treatment;
mean annual HbA1c and fructosamine values before and after CSII treatment; and
hypoglycemia frequency and symptoms. RESULTS: The most common reason for pump
treatment was brittle diabetes (74.1%), followed by frequent or severe
hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were
irregular food intake times for professional reasons (20.2%), dawn phenomenon
(15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and
gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and
fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced
hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia
occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia
unawareness was found in 21%. Hypoglycemia was more common at treatment start,
and its frequency rapidly decreased thereafter. CONCLUSION: CSII therapy provides
a better glycemic control than MDII treatment. Specific patient training and fine
adjustment of insulin infusion doses are required to prevent hypoglycemic
episodes, which are the most common complications, mainly at the start of
treatment.
PMID- 24355549
TI - Results of repeated transsphenoidal surgery in Cushing's disease. Long-term
follow-up.
AB - OBJECTIVE: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's
disease (CD). However, the best treatment option when hypercortisolism persists
or recurs remains unknown. The aim of this study was to analyze the short and
long-term outcome of repeat TSS in this situation and to search for response
predictors. PATIENTS AND METHODS: Data from 26 patients with persistent (n=11) or
recurrent (n=15) hypercortisolism who underwent repeat surgery by a single
neurosurgeon between 1982 and 2009 were retrospectively analyzed. Remission was
defined as normalization of urinary free cortisol (UFC) levels, and recurrence as
presence of elevated UFC levels after having achieved remission. The following
potential outcome predictors were analyzed: adrenal status (persistence or
recurrence) after initial TSS, tumor identification in imaging tests, degree of
hypercortisolism before repeat TSS, same/different surgeon in both TSS, and time
to repeat surgery. RESULTS: Immediate postoperative remission was achieved in 12
patients (46.2%). Five of the 10 patients with available follow-up data relapsed
after surgery (median time to recurrence, 13 months). New hormone deficiencies
were seen in seven patients (37%), and two patients had cerebrospinal fluid
leakage. No other major complications occurred. None of the preoperative factors
analyzed was predictive of surgical outcome. CONCLUSIONS: When compared to
initial surgery, repeat TSS for CD is associated to a lower remission rate and a
higher risk of recurrence and complications. Further studies are needed to define
outcome predictors.
PMID- 24355550
TI - Selection and dynamic metabolic response of rat biomarkers by metabonomics and
multivariate statistical analysis combined with GC-MS.
AB - Depression is a common complex psychiatric disorder but its pathophysiological
mechanism is not yet fully understood. Metabonomics by GC-MS and multivariate
statistical analysis were used to select potential biomarkers associated with
CUMS (chronic unpredictable mild stress) depression. The dynamic metabolic
changes in rat serum were investigated to find potential disease biomarkers and
to investigate the pathology of depression induced by the CUMS depression model.
The changes in behavior and serum metabolic profiles were investigated during a
three-week CUMS exposure. Serum samples were collected on days 0, 6, 9, 12, 15
and 21, and the serum metabolic profiling was carried out using GC-MS, followed
by multivariate analysis. The potential biomarkers were screened from metabolites
by principal component analysis and correlation analysis. The peak area of
potential biomarkers was used to identify changes in depression in rats and
describe their dynamics. Exposure to CUMS for three weeks caused depression-like
behavior in rats, as indicated by significant decreases in weight gain, sucrose
consumption, ambulation number and rearing numbers. Six potential biomarkers in
serum, including glycine (Gly), glutamic acid (Glu), fructose, citric acid,
glucose and hexadecanoic acid, were subjected to screening by metabonomics and
multivariate statistical analysis. It was found that fructose, glucose and Gly
were increased in the model group, while hexadecanoic acid, Glu and citric acid
were reduced in the model group. According to the results of principal component
analysis and correlation analysis, the correlation coefficient between the
behavior scores and potential biomarkers in serum were all more than 0.9. This
result suggests that the progression of depression may be associated with
perturbation of glycometabolism, amino acid metabolism and energy metabolism.
Gly, Glu, fructose, citric acid, glucose and hexadecanoic acid appear to be
suitable quantitative diagnostic biomarkers for depression. The representative
and unique nature of these biomarkers needs to be verified by pharmacological
experiments, including molecular pharmacology investigations of enzymes or genes.
PMID- 24355551
TI - Withdrawal induces distinct patterns of FosB/?FosB expression in outbred Swiss
mice classified as susceptible and resistant to ethanol-induced locomotor
sensitization.
AB - Chronic drug exposure and drug withdrawal induce expressive neuronal plasticity
which could be considered as both functional and pathological responses. It is
well established that neuronal plasticity in the limbic system plays a pivotal
role in relapse as well as in compulsive characteristics of drug addiction.
Although increases in FosB/DeltaFosB expression constitute one of the most
important forms of neuronal plasticity in drug addiction, it is unclear whether
they represent functional or pathological plasticity. It is of noteworthy
importance the individual differences in the transition from recreational use to
drug addiction. These differences have been reported in studies involving the
ethanol-induced locomotor sensitization paradigm. In the present study we
investigated whether sensitized and non-sensitized mice differ in terms of
FosB/DeltaFosB expression. Adult male outbred Swiss mice were daily treated with
ethanol or saline for 21 days. According to the locomotor activity in the
acquisition phase, they were classified as sensitized (EtOH_High) or non
sensitized (EtOH_Low). After 18 h or 5 days, their brains were processed for
FosB/DeltaFosB immunohistochemistry. On the 5th day of withdrawal, we could
observe increased FosB/DeltaFosB expression in the EtOH_High group (in the motor
cortex), in the EtOH_Low group (in the ventral tegmental area), and in both
groups (in the striatum). Differences were more consistent in the EtOH_Low group.
Therefore, behavioral variability observed in the acquisition phase of ethanol
induced locomotor sensitization was accompanied by differential neuronal
plasticity during withdrawal period. Furthermore, distinct patterns of
FosB/DeltaFosB expression detected in sensitized and non-sensitized mice seem to
be more related to withdrawal period rather than to chronic drug exposure.
Finally, increases in FosB/DeltaFosB expression during withdrawal period could be
considered as being due to both functional and pathological plasticity.
PMID- 24355553
TI - FACS selection of valuable mutant mouse round spermatids and strain rescue via
round spermatid injection.
AB - Round spermatid injection (ROSI) into mammalian oocytes can result in the
development of viable embryos and offspring. One current limitation to this
technique is the identification of suitable round spermatids. In the current
paper, round spermatids were selected from testicular cells with phase contrast
microscopy (PCM) and fluorescence-activated cell sorting (FACS), and ROSI was
performed in two strains of mice. The rates of fertilization, embryonic
development and offspring achieved were the same in all strains. Significantly,
round spermatids selected by PCM and FACS were effectively used to rescue the
infertile Pten-null mouse. The current results indicate that FACS selection of
round spermatids can not only provide high-purity and viable round spermatids for
use in ROSI, but also has no harmful effects on the developmental capacity of
subsequently fertilized embryos. It was concluded that round spermatids selected
by FACS are useful for mouse strain rederivation and rescue of infertile males;
ROSI should be considered as a powerful addition to the armamentarium of assisted
reproduction techniques applicable in the mouse.
PMID- 24355552
TI - Changes in gene expression within the extended amygdala following binge-like
alcohol drinking by adolescent alcohol-preferring (P) rats.
AB - The objective of this study was to determine changes in gene expression within
the extended amygdala following binge-like alcohol drinking by male adolescent
alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given
concurrent access to 15 and 30% ethanol for 3 one-h sessions/day for 5
consecutive days/week for 3 weeks. Rats were killed by decapitation 3 h after the
first ethanol access session on the 15th day of drinking. RNA was prepared from
micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of
the amygdala (CeA). Ethanol intakes were 2.5-3.0 g/kg/session. There were 154 and
182 unique named genes that significantly differed (FDR=0.2) between the water
and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO)
analyses indicated that adolescent binge drinking produced changes in biological
processes involved with cell proliferation and regulation of cellular structure
in the Acb-sh, and in neuron projection and positive regulation of cellular
organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb
sh, there were several major intracellular signaling pathways (e.g., cAMP
mediated and protein kinase A signaling pathways) altered by adolescent drinking,
with 3-fold more genes up-regulated than down-regulated in the alcohol group. The
cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol
group. Weighted gene co-expression network analysis indicated significant G
protein coupled receptor signaling and transmembrane receptor protein kinase
signaling categories in the Acb-sh and CeA, respectively. Overall, the results of
this study indicated that binge-like alcohol drinking by adolescent P rats is
differentially altering the expression of genes in the Acb-sh and CeA, some of
which are involved in intracellular signaling pathways and may produce changes in
neuronal function.
PMID- 24355554
TI - Cumulative teen birth rates among girls in foster care at age 17: an analysis of
linked birth and child protection records from California.
AB - This study used linked foster care and birth records to provide a longitudinal,
population-level examination of the incidence of first and repeat births among
girls who were in foster care at age 17. Girls in a foster care placement in
California at the age of 17 between 2003 and 2007 were identified from statewide
child protection records. These records were probabilistically matched to vital
birth records spanning the period from 2001 to 2010. Linked data were used to
estimate the cumulative percentage of girls who had given birth before age 20.
Birth rates and unadjusted risk ratios were generated to characterize foster care
experiences correlated with heightened teen birth rates. Between 2003 and 2007 in
California, there were 20,222 girls in foster care at age 17. Overall, 11.4% had
a first birth before age 18. The cumulative percentage who gave birth before age
20 was 28.1%. Among girls who had a first birth before age 18, 41.2% had a repeat
teen birth. Significant variations by race/ethnicity and placement-related
characteristics emerged. Expanded data and rigorous research are needed to
evaluate prevention efforts and ensure parenting teens are provided with the
needed services and supports.
PMID- 24355555
TI - Identification and characterization of microRNAs in the crab-eating macaque
(Macaca fascicularis) using transcriptome analysis.
AB - MicroRNAs (miRNAs), with an average length between 16 nt and 26 nt, are small non
coding RNAs that can repress gene expression on the post-transcriptional level.
Macaca fascicularis (M. fascicularis), one of the most important nonhuman primate
animal models, is widely used in basic and applied preclinical research,
especially in studies that involve neuroscience and disease. However, due to the
lack of a complete genome sequence, the miRNAs in M. fascicularis have not been
completely characterized. In this study, 86 putative M. fascicularis miRNAs were
identified using a strategy of our design. The expression of some of these miRNAs
in the tissue was confirmed by qRT-PCR. The function and pathway of their
targeted genes were analyzed to reveal the potential relevance of miRNA
regulation on diseases and physiological processes. The current study provides
insight into potential miRNAs and forms a useful knowledge base for the future
understanding of the function of miRNAs in M. fascicularis.
PMID- 24355556
TI - A novel homozygous no-stop mutation in G6PC gene from a Chinese patient with
glycogen storage disease type Ia.
AB - Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive genetic
disorder resulting in hypoglycemia, hepatomegaly and growth retardation. It is
caused by mutations in the G6PC gene encoding Glucose-6-phosphatase. To date,
over 80 mutations have been identified in the G6PC gene. Here we reported a novel
mutation found in a Chinese patient with abnormal transaminases, hypoglycemia,
hepatomegaly and short stature. Direct sequencing of the coding region and
splicing-sites in the G6PC gene revealed a novel no-stop mutation, p.*358Yext*43,
leading to a 43 amino-acid extension of G6Pase. The expression level of mutant
G6Pase transcripts was only 7.8% relative to wild-type transcripts. This mutation
was not found in 120 chromosomes from 60 unrelated healthy control subjects using
direct sequencing, and was further confirmed by digestion with Rsa I restriction
endonuclease. In conclusion, we revealed a novel no-stop mutation in this study
which expands the spectrum of mutations in the G6PC gene. The molecular genetic
analysis was indispensable to the diagnosis of GSD-Ia for the patient.
PMID- 24355557
TI - Investigating GSTT1 and GSTM1 null genotype as the risk factor of diabetes type 2
retinopathy.
AB - BACKGROUND: Diabetes is one of the multifactorial disorders with genetics and
environmental factors playing important role in its cause. In diabetes, the
defects in cellular metabolism results in increasing free radicals. These
radicals react with other vital cellular molecules which are responsible in
diabetes side effects. Human glutathione S-transferases (GST) are a family of
enzymes that catalyses conjugation of electrophilic substances with glutathione.
In this research the deletion of two of the most important genes of this family;
GSTT1 and GSTM1 genes was investigated as the risk factor for diabetes mellitus
type II and one of its most important complications; retinopathy. MATERIAL AND
METHODS: In this study deletion of GSTT1 and GSTM1 genes in 57 diabetics'
patients with retinopathy and 58 diabetic peoples without retinopathy was
examined. DNA was extracted from peripheral blood and then multiplex PCR was
performed following agarose gel electrophoresis to detect GSTT1 and GSTM1 null
genotypes. Data were analyzed with SPSS v16 software. RESULTS: The results
indicated that there was significant relationship between GSTM1 null genotype
with retinopathy side effect of diabetes type 2. While there was no significant
relationship between GSTT1 null genotypes with retinopathy in diabetes type 2.
CONCLUSION: Significant correlation between GSTM1 null genotype and retinopathy
in this and other studies could indicate this fact that impair cellular
metabolism result in increase free radicals and oxidative pressure. Therefore,
GST null genotypes may result in decrease antioxidant capacity which causes side
effects of diabetes. Considering the performance of different classes of GST null
genotypes additional studies are required to confirm this study.
PMID- 24355558
TI - [Update on gastroesophageal reflux disease].
AB - Gastroesophageal reflux disease is a highly frequent disorder classically
characterized by the presence of heartburn and/or acid regurgitation that
improves with drug therapy that reduces acid content in the stomach. However,
especially in patients with non-erosive disease, response to proton pump
inhibitors is unsatisfactory in approximately 1 out of 3 patients, and
consequently, in these patients, it is important to establish a definitive
diagnosis and an alternative therapeutic strategy. In the last few years,
advances have been made in knowledge of the physiopathology of reflux, such as
identification of the role of the acid pocket in producing reflux, technological
advances that allow differentiation among acid reflux, non-acid reflux and
slightly acid reflux, and advances in the treatment of reflux with drugs that
attempt to act on the barrier function of the esophagogastric junction.
PMID- 24355559
TI - Peer influence on speeding behaviour among male drivers aged 18 and 28.
AB - Despite extensive research, preventive efforts and general improvements in road
safety levels, the accident risk of young male drivers remains increased. Based
on a standardized survey of a random sample of 2018 male drivers at the age of 18
and 28, this study looked into attitudes and behaviours related to traffic
violations of male drivers. More specifically, the role of peer influence on
speeding was examined in both age groups. In regression analyses it could be
shown that the descriptive subjective norm, i.e., the perception of friends'
speeding, was the most important predictor of speeding in both age groups. Other
significant factors were: negative attitude towards speed limits, injunctive
subjective norm, and the perceived risk of having an accident when speeding. In
the older age group it was more common to drive faster than allowed and their
speeding was largely in line with the perceived level of their friends' speeding.
In the younger age group a higher discrepancy between own and friends' speeding
was found indicating that young male drivers are socialized into increased
speeding behaviour based on peer pressure. By contrast for the 28-year-olds peer
pressure mainly seems to maintain or justify individual speeding behaviour. It is
suggested that preventive measures should take these different influences of peer
pressure into account by using a peer-based approach for the 18-year-olds and a
more individual approach for the 28-year-olds.
PMID- 24355561
TI - [Crohn's disease and erythema nodusum: is exclusive enteral nutrition useful?].
PMID- 24355560
TI - Molecular patterning of the mammalian dentition.
AB - Four conserved signaling pathways, including the bone morphogenetic proteins
(Bmp), fibroblast growth factors (Fgf), sonic hedgehog (Shh), and wingless
related (Wnt) pathways, are each repeatedly used throughout tooth development.
Inactivation of any of these resulted in early tooth developmental arrest in
mice. The mutations identified thus far in human patients with tooth agenesis
also affect these pathways. Recent studies show that these signaling pathways
interact through positive and negative feedback loops to regulate not only
morphogenesis of individual teeth but also tooth number, shape, and spatial
pattern. Increased activity of each of the Fgf, Shh, and canonical Wnt signaling
pathways revitalizes development of the physiologically arrested mouse diastemal
tooth germs whereas constitutive activation of canonical Wnt signaling in the
dental epithelium is able to induce supernumerary tooth formation even in the
absence of Msx1 and Pax9, two transcription factors required for normal tooth
development beyond the early bud stage. Bmp4 and Msx1 act in a positive feedback
loop to drive sequential tooth formation whereas the Osr2 transcription factor
restricts Msx1-mediated expansion of the mesenchymal odontogenic field along both
the buccolingual and anteroposterior axes to pattern mouse molar teeth in a
single row. Moreover, the ectodermal-specific ectodysplasin (EDA) signaling
pathway controls tooth number and tooth shape through regulation of Fgf20
expression in the dental epithelium, whereas Shh suppresses Wnt signaling through
a negative feedback loop to regulate spatial patterning of teeth. In this
article, we attempt to integrate these exciting findings in the understanding of
the molecular networks regulating tooth development and patterning.
PMID- 24355562
TI - [Complete vascular ring: prenatal diagnosis of double aortic arch].
PMID- 24355563
TI - Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer
cells via inhibition of canonical Wnt signaling.
AB - Research on existing drugs often discovers novel mechanisms of their action and
leads to the expansion of their therapeutic scope and subsequent remarketing. The
Wnt signaling pathway is of the immediate therapeutic relevance, as it plays
critical roles in cancer development and progression. However, drugs which
disrupt this pathway are unavailable despite the high demand. Here we report an
attempt to identify antagonists of the Wnt-FZD interaction among the library of
the FDA-approved drugs. We performed an in silico screening which brought up
several potential antagonists of the ligand-receptor interaction. 14 of these
substances were tested using the TopFlash luciferase reporter assay and four of
them identified as active and specific inhibitors of the Wnt3a-induced signaling.
However, further analysis through GTP-binding and beta-catenin stabilization
assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the
signaling at downstream levels. We further describe the previously unknown
inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and
provide data demonstrating its efficiency in suppressing growth of Wnt-dependent
triple-negative breast cancer cells. These data provide a basis for further
investigations of the efficiency of clofazimine in treatment of Wnt-dependent
cancers.
PMID- 24355564
TI - (R,R')-4'-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand
internalization and impairs cancer cell motility.
AB - (R,R')-4'-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and
apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR)
activation. The synthetic CB1R inverse agonist, AM251, has been shown to block
the anti-mitogenic effect of MNF in these cells; however, AM251 is also an
agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose
upregulation contributes to carcinogenesis. Here, we investigated the role of MNF
in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by
focusing first on internalization of the fluorescent ligand Tocrifluor 1117
(T1117). Initial results indicated that cell pretreatment with GPR55 agonists,
including the atypical cannabinoid O-1602 and l-alpha-lysophosphatidylinositol,
dose-dependently reduced the rate of cellular T1117 uptake, a process that was
sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O
1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2
and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2
phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a
coordinated negative regulation of AM251 and O-1602 inducible processes,
including changes in cellular morphology and cell migration using scratch wound
healing assay. This study shows for the first time that MNF impairs GPR55
mediated signaling and, therefore, may have therapeutic potential in the
management of cancer.
PMID- 24355566
TI - TREM2 and the neuroimmunology of Alzheimer's disease.
AB - Late-onset Alzheimer's disease (AD) is a sporadic disorder with increasing
prevalence in aging. The E4 allele of Apolipoprotein E(ApoEE4) was the only known
major risk factor for late onset AD. Recently, two groups of investigators
independently identified variants of the TREM2 gene, encoding triggering receptor
expressed on myeloid cells 2 as causing increased susceptibility to late onset AD
with an odds ratio similar to that of ApoEE4. TREM2 is a receptor expressed on
innate immune cells. Using a novel technology called Direct RNA Sequencing
wedetermined the quantitative transcriptome of microglia, the principal innate
neuroimmune cells and confirmed that TREM2 is a major microglia-specific gene in
the central nervous system. Over the past several years we have shown that
microglia play a dichotomous role in AD. Microglia can be protective and promote
phagocytosis, degradation and ultimately clearance of Abeta, the pathogenic
protein deposited in the brains of Alzheimer's patients. However, with disease
progression, microglia become dysfunctional, release neurotoxins, lose their
ability to clear Abeta and produce pro-inflammatory cytokines that promote Abeta
production and accumulation. TREM2 has been shown to regulate the phagocytic
ability of myeloid cells and their inflammatory response. Here we propose that
the mechanism(s) by which TREM2 variants cause Alzheimer's disease are via down
regulation of the Abeta phagocytic ability of microglia and by dysregulation of
the pro-inflammatory response of these cells. Based on our discussion we propose
that TREM2 is a potential therapeutic target for stopping ordelaying progression
of AD.
PMID- 24355567
TI - PGE2/EP4 signaling in peripheral immune cells promotes development of
experimental autoimmune encephalomyelitis.
AB - Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory
autoimmune disease model of multiple sclerosis (MS). The inflammatory process is
initiated by activation and proliferation of T cells and monocytes and by their
subsequent migration into the central nervous system (CNS), where they induce
demyelination and neurodegeneration. Prostaglandin E2 (PGE2) - synthesized by
cyclooxygenase 2 (COX-2) - has both pro- and anti-inflammatory potential, which
is translated via four different EP receptors. We hypothesized that PGE2
synthesized in the preclinical phase by peripheral immune cells exerts pro
inflammatory properties in the EAE model. To investigate this, we used a bone
marrow transplantation model, which enables PGE2 synthesis or EP receptor
expression to be blocked specifically in peripheral murine immune cells. Our
results reveal that deletion of COX-2 or its EP4 receptor in bone marrow-derived
cells leads to a significant delay in the onset of EAE. This effect is due to an
impaired preclinical inflammatory process indicated by a reduced level of the T
cell activating interleukin-6 (IL-6), reduced numbers of T cells and of the T
cell secreted interleukin-17 (IL-17) in the blood of mice lacking COX-2 or EP4 in
peripheral immune cells. Moreover, mice lacking COX-2 or EP4 in bone marrow
derived cells show a reduced expression of matrix metalloproteinase 9 (MMP9),
which results in decreased infiltration of monocytes and T cells into the CNS. In
conclusion, our data demonstrate that PGE2 synthesized by monocytes in the early
preclinical phase promotes the development of EAE in an EP4 receptor dependent
manner.
PMID- 24355565
TI - Role of metabotropic glutamate receptors in the regulation of pancreatic
functions.
AB - The pancreas consists of two major divisions, the exocrine and the endocrine
pancreas. Recent data from our laboratory have shown that the functions of the
two divisions are under modulatory regulation by separate neurocircuits that
originate in the dorsal motor nucleus of the vagus (DMV). Metabotropic glutamate
receptors (mGluRs) are expressed throughout the central nervous system and have
been implicated in the modulation of synaptic transmission. mGluRs consist of
three groups of receptors, which can be distinguished based on their
pharmacological properties and second messenger systems. Group I mGluRs
predominantly increase, whereas group II and III mGluRs decrease synaptic
transmission. Group II and group III mGluRs are present on excitatory and
inhibitory synaptic terminals impinging on pancreas-projecting DMV neurons. We
have shown that group II mGluRs regulate both exocrine pancreatic secretions and
insulin release, whereas group III mGluRs only regulate insulin release. Several
mGluR agonists and antagonists have been shown to have clinical uses for
disorders accompanied by abnormal synaptic transmission, including anxiety and
Parkinson's disease. Moreover, a negative allosteric modulator of Group I mGluRs
is effective in alleviating symptoms of gastro-esophageal reflux disease (GERD).
Since the role of the three mGluR groups in mediating different gastrointestinal
(GI) functions appears to be highly specific, the use of agonists or antagonists
directed at a single receptor group could potentially provide highly selective
targets for the treatment of GI disorders including GERD, functional dyspepsia
and acute pancreatitis.
PMID- 24355568
TI - Ipsilateral intracranial edema associated with drainage patterns of dural
arteriovenous fistula.
AB - BACKGROUND: Massive ipsilateral edema in patients with cerebral dural
arteriovenous fistula (DAVF) is poorly documented. The present study better
characterizes this condition through assessment of venous anatomy and potential
underlying mechanisms. METHODS: One hundred and two consecutive patients
diagnosed with DAVF and admitted to the Huashan Hospital from 2006 to 2012 were
retrospectively reviewed for the clinical and radiologic data, and those with
ipsilateral edema were recruited. An edema scale was calculated from the
locations with edema on magnetic resonance imaging. We created a reflux anatomic
venous scale (RAVS, including veins of Labbe, Sylvian, and Troland) based on DSA.
Two experienced interventional neuroradiologists independently assessed the
images and then reached consensus. The Spearman nonparametric rank correlation
was performed to analyze the correlation between edema scale and RAVS. RESULTS:
Seven patients (mean 61 +/- 13 years; 4 men:3 women) with ipsilateral
intracranial edema were finally included. DAVF in transverse sinus with reflux
flow initially in vein of the Labbe was seen in all patients. Increased edema
scale was significantly correlated with increased RAVS (Spearman rho = .856, P =
.014). CONCLUSION: The present study indicated that severe ipsilateral edema,
with reflux flow initially in vein of the Labbe, was associated with the
increased number of reflux anatomic veins in transverse sinus DAVF.
PMID- 24355569
TI - Accumulation of trace metals in grey mangrove Avicennia marina fine nutritive
roots: the role of rhizosphere processes.
AB - Mangrove sediment has long been recognized as being important in restricting the
mobility of contaminants in estuarine environments. To investigate the role of
rhizosphere processes in the accumulation of trace metals in mangrove fine
nutritive roots, the mangrove sediments and associated fine nutritive roots are
collected from five major embayments of Sydney estuary (Australia) for
geochemical studies. In this estuary Avicennia marina sediments are accumulating
large quantities of trace metals due to presence of abundant fine sediment (<62.5
MUm) and organic matter as well as anthropogenic input. Accumulation of trace
metals in fine nutritive roots responds to total sediment chemistry mainly due to
rhizosphere sediment geochemical processes resulting in a strong linear
correlation between metal concentrations in fine nutritive roots vs. total and
bio-available contents in sediments. Accumulation of trace metals in fine
nutritive roots is almost always exceeds rhizosphere total sediment metal
concentrations.
PMID- 24355570
TI - Impact of total organic carbon (in sediments) and dissolved organic carbon (in
overlying water column) on Hg sequestration by coastal sediments from the central
east coast of India.
AB - Total organic carbon (TOC) (in sediment) and dissolved organic matter (DOM) (in
water column) play important roles in controlling the mercury sequestration
process by the sediments from the central east coast of India. This toxic metal
prefers to associate with finer size particles (silt and clay) of sediments.
Increasing concentrations of DOM in overlying water column may increase
complexation/reduction processes of Hg(2+) within the water column and decrease
the process of Hg sequestration by sediments. However, high concentrations of DOM
in water column may increase Hg sequestration process by sediments.
PMID- 24355571
TI - Assessment of photochemical processes in marine oil spill fingerprinting.
AB - Understanding weathering processes plays a critical role in oil spill forensics,
which is based on the comparison of the distributions of selected compounds
assumed to be recalcitrant and/or have consistent weathering transformations.
Yet, these assumptions are based on limited laboratory and oil-spill studies.
With access to additional sites that have been oiled by different types of oils
and exposures, there is a great opportunity to expand on our knowledge about
these transformations. Here, we demonstrate the effects of photooxidation on the
overall composition of spilled oils caused by natural and simulated sunlight, and
particularly on the often used polycyclic aromatic hydrocarbons (PAHs) and the
biomarker triaromatic steranes (TAS). Both laboratory and field data from oil
released from the Macondo well oil following the Deepwater Horizon disaster
(2010), and heavy fuel-oil from the Prestige tanker spill (2002) have been
obtained to improve the data interpretation of the typical fingerprinting
methodology.
PMID- 24355572
TI - Endosomal transport of septin mRNA and protein indicates local translation on
endosomes and is required for correct septin filamentation.
AB - Endosomes transport lipids and proteins over long distances by shuttling along
microtubules. They also carry mRNAs on their surface, but the precise molecular
function of this trafficking process is unknown. By live cell imaging of
polarized fungal hyphae, we show microtubule-dependent transport of septin mRNA
and encoded septin protein on the same shuttling endosomes. Consistent with the
hypothesis that septin mRNA is translated on endosomes, the accumulation of
septin protein on endosomes requires the recruitment of septin mRNA. Furthermore,
ribosomal proteins co-localise with shuttling endosomes, but only if mRNA is
present. Importantly, endosomal trafficking is essential for an efficient
delivery of septin protein to filaments at growth poles, a process necessary to
establish unipolar growth. Thus, we propose that local mRNA translation loads
endosomes with septins for assembly and efficient delivery to septin filaments.
PMID- 24355573
TI - Emergence of OXA-72-producing Acinetobacter pittii clinical isolates.
PMID- 24355574
TI - Galactosylation of human erythropoietin produced by chimeric chickens expressing
galactosyltransferase.
AB - Human erythropoietin produced in the egg white of chimeric chicken contains N
glycan with lower amounts of terminal galactose and sialic acid; therefore, the
chicken galactosyltransferase gene was introduced together with the human
erythropoietin gene by a retroviral vector. We found that erythropoietin
accumulated in the egg white was partially galactosylated.
PMID- 24355575
TI - Associations between building design, point-of-decision stair prompts, and stair
use in urban worksites.
AB - OBJECTIVE: Incidental forms of physical activity such as stair use offer frequent
opportunities for energy expenditure and may contribute to the prevention and
control of chronic diseases. This study analyzes the associations between
building characteristics, stair prompts, and stair use in large urban worksites.
METHODS: Bootstrapped generalized mixed models were used to analyze self-reported
stair use, using data from 1348 surveys of city employees and fourteen building
assessments conducted in New York City in 2012. RESULTS: 57% of respondents
reported climbing >=1 flights of stairs daily at the workplace. Model results
show that stair prompts were associated with a 3.21 increased likelihood of stair
use. Naturally lit stairwells and stairwell visibility were also positively
associated. Higher floor residency and BMI were negatively related, as were
gender, stairwell distance from lobby entrances, the total number of floors in
each building, and building averages for BMI and gender. Residual heterogeneity
measured by adjusted median odds ratios indicates that buildings can have a
moderate effect on the likelihood of stair use beyond those of individual
characteristics. CONCLUSIONS: Specific building features and stair prompts may
potentially be leveraged to positively influence rates of incidental physical
activity and contribute to improvements in population health.
PMID- 24355576
TI - Long-term effects of a home-based smoking prevention program on smoking
initiation: a cluster randomized controlled trial.
AB - OBJECTIVE: The aims of the study were to evaluate the long-term effects of a home
based smoking prevention program 'Smoke-free Kids' during preadolescence on
smoking initiation during adolescence and to test the potential moderating role
of parental smoking, socioeconomic status, and asthma. METHOD: In 2008, 1478 9
11year old children and their mothers were recruited from 418 elementary schools
in the Netherlands. An independent statistician randomly allocated schools to one
of the two conditions using a 1:1 ratio (single blind): 728 children in the
intervention and 750 in the control condition. The intervention condition
received five activity modules, including a communication sheet for mothers, by
mail at four-week intervals and one booster module one year after baseline. The
control condition received a fact-based intervention only. Intention-to-treat
analysis was performed on 1398 non-smoking children at baseline. RESULTS: In the
intervention 10.8% of the children started smoking compared to 12% in the control
condition. This difference was non-significant (odds ratio=0.90, 95% confidence
interval=0.63-1.27). No moderating effects were found. CONCLUSION: No effects on
smoking initiation after 36months were found. Perhaps, the program was
implemented with children that were too young. Programs closer to the age of
smoking onset should be tested.
PMID- 24355577
TI - Contribution of different Ca2+ channels to the acrosome reaction-mediated
initiation of sperm motility in the newt Cynops pyrrhogaster.
AB - Initiation of sperm motility in urodeles, which is induced by a sperm motility
initiating substance (SMIS) in the sequestered granules on the surface of egg
jelly, is mediated by the acrosome reaction (AR), which is triggered by an AR
inducing substance (ARIS) on a sheet-like structure. Details of the unique
process of the interaction between egg jelly and sperm in these species is still
unclear. The current study showed the fine structure of egg jelly in the newt
Cynops pyrrhogaster, a urodele species, revealing that its outer surface was
covered by a sheet-like structure of approximately 0.29 MUm in thickness.
Granules of approximately 2 MUm in diameter with small particles of approximately
54 nm were attached to its surface and distributed inhomogeneously just beneath
the sheet-like structure. Emission spectrometry revealed that the Ca2+
concentration was maintained at a high level compared with that of the blood
plasma and the vas deferens fluid, suggesting that egg jelly is a reliable source
of Ca2+ for the sperm-egg interaction. Blockers of the T-type voltage-dependent
Ca2+ channel (VDCC), but not the L-type VDCC, inhibited both AR and initiation of
sperm motility. Conversely, Ni+, which affects the alpha1 H subunit of T-type
VDCC, only inhibited the initiation of sperm motility. These data suggest that,
in response to ARIS and SMIS, sequential gating of distinct Ca2+ channels occurs
in the AR, followed by the initiation of sperm motility on the surface of the egg
jelly in C. pyrrhogaster at fertilization.
PMID- 24355578
TI - Bad medicine: restless legs syndrome.
PMID- 24355579
TI - Cancer incidence and mortality continue to fall in US, report finds.
PMID- 24355580
TI - Deprivation is restored to funding formula for commissioning groups.
PMID- 24355581
TI - EU agrees rules to allow most e-cigarettes to be sold as consumer products.
PMID- 24355582
TI - [Have we moved on to the DSM-5? A debate with clinical, social and financial
implications].
PMID- 24355583
TI - Endoscopic microdebrider-assisted inferior turbinoplasty with and without
posterior nasal neurectomy.
AB - OBJECTIVE: Endoscopic microdebrider-assisted inferior turbinoplasty (EMAIT) has
been recognized as an efficient surgical technique in the management of
hypertrophied inferior turbinate. In an attempt to further increase surgical
successful outcomes, posterior nasal neurectomy (PNN) was developed. The aim of
this retrospective case-control study was to assess the position of PNN in the
surgery of hypertrophied turbinate. METHODS: Seventy patients were assigned to
the two treatment groups: Group A (EMAIT) and Group B (EMAIT and PNN). Subjective
outcomes were represented by symptom score and quality of life scores
(Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ). Objective outcomes
were nasal resistance, saccharin transit time and acoustic rhinometry parameters.
RESULTS: The survey demonstrated that symptoms and objective parameters improved
postoperatively in both groups, with no statistical significant differences in
objective and subjective outcomes between the surgical groups. CONCLUSION: The
addition of PNN appears to offer no additional benefit in the subjective and
objective outcome related with surgery of hypertrophied inferior turbinate.
However, longer follow-up studies and larger number of patients are required in
order to validate our results.
PMID- 24355584
TI - Middle ear malformations in identical twins.
AB - The majority of the congenital anomalies of middle ear are solitary and a non
hereditary. We report cases of identical twins with congenital incudo-stapedial
disconnection. Case 1 was an 8-year-old girl. Hearing impairment was identified
at the age of three. She was referred to our university hospital in April 2005.
Pure-tone audiogram showed conductive hearing impairments. Computed tomography
(CT) revealed the incudo-stapedial disconnections in both ears. The exploratory
tympanotomies on the right and left ears were performed in May and July 2005,
respectively. The surgical findings showed absence of the long process and
presence of the lenticular process of the incus in both ears. After the
reconstructions of ossicular chain, the hearing of both ears improved. Case 2 was
an 11-year-old girl. The hearing impairment of the right ear was identified in
May 2008. She was referred to our university hospital three months later. Pure
tone audiogram showed the conductive hearing impairment in the right ear. CT
revealed the incudo-stapedial disconnection in the right ear. The surgery showed
the same findings as those of case 1. Anomalies of both cases suggest that the
lenticular process of the incus and the stapes originate from a common
primordium.
PMID- 24355585
TI - Nicotine decreases the activity of glutamate transporter type 3.
AB - Nicotine, the main ingredient of tobacco, elicits seizures in animal models and
cigarette smoking is regarded as a behavioral risk factor associated with
epilepsy or seizures. In the hippocampus, the origin of nicotine-induced
seizures, most glutamate uptake could be performed primarily by excitatory amino
acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy
and EAAT3 downregulation has been reported. Therefore, we hypothesized that
nicotine may elicit seizures through the attenuation of EAAT3 activity. We
investigated chronic nicotine exposure (72 h) cause reduction of the activity of
EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp.
The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were
also determined. Nicotine (0.001-1 MUM) resulted in a time- and dose-dependent
decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of
0.03 MUM or higher and at an exposure time of 72 h. Vmax on the glutamate
response was significantly reduced in the nicotine group (0.03 MUM for 72 h), but
the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed
oocytes (0.03 MUM for 72 h) were pretreated with phorbol-12-myristate-13-acetate
(PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was
abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C)
significantly reduced basal EAAT3 activity, but there were no significant
differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine
groups. Similar response patterns were observed among PI3K inhibitors (wortmannin
and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study
suggests that nicotine decreases EAAT3 activity, and that this inhibition seems
to be dependent on PKC and PI3K. Our results may provide an additional mechanism
for nicotine-induced seizure.
PMID- 24355586
TI - Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular
carcinoma via Wnt/beta-catenin pathway.
AB - Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant, involved
in the progression of many cancers, including liver cancer. However, the
underlying mechanism(s) of DDT, especially how low doses DDT cause liver cancer,
is poorly understood. In this study, we evaluated the impact of p,p'-DDT on the
growth of hepatocellular carcinoma using both in vitro and in vivo models. The
present data indicated that the proliferation of HepG2 cells was strikingly
promoted after exposed to p,p'-DDT for 4 days. In addition, reactive oxygen
species (ROS) content was significantly elevated, accompanied with inhibitions of
gamma-glutamylcysteine synthetase (gamma-GCS) and superoxide dismutase (SOD)
activities. Interestingly, the levels of beta-catenin and its downstream target
genes (c-Myc and CyclinD1) were significantly up-regulated, and co-treatment of
NAC, the ROS inhibitor, inhibited these over-expressed proteins. Moreover, the
p,p'-DDT-stimulated proliferation of HepG2 cells could be reversed after NAC or
beta-catenin siRNA co-treatment. Likewise, p,p'-DDT treatment increased the
growth of tumor in nude mice, stimulated oxidative stress and Wnt/beta-catenin
pathway. Our study indicates that low doses p,p'-DDT exposure promote the growth
of hepatocellular carcinoma via Wnt/beta-catenin pathway which is activated by
oxidative stress. The finding suggests an association between low dose DDT
exposure and liver cancer growth.
PMID- 24355587
TI - Separating esterase targets of organophosphorus compounds in the brain by
preparative chromatography.
AB - Low level exposure to organophosphorus esters (OPs) may cause long-term
neurological effects and affect specific cognition domains in experimental
animals and humans. Action on known targets cannot explain most of these effects
by. Soluble carboxylesterases (EC 3.1.1.1) of chicken brain have been kinetically
discriminated using paraoxon, mipafox and phenylmethyl sulfonylfluoride as
inhibitors and phenyl valerate as a substrate. Three different enzymatic
components were discriminated and called Ealpha, Ebeta and Egamma. In this work,
a fractionation procedure with various steps was developed using protein native
separation methods by preparative HPLC. Gel permeation chromatography followed by
ion exchange chromatography allowed enriched fractions with different kinetic
behaviors. The soluble chicken brain fraction was fractionated, while total
esterase activity, proteins and enzymatic components Ealpha, Ebeta and Egamma
were monitored in each subfraction. After the analysis, 13 fractions were pooled
and conserved. Preincubation of the soluble chicken brain fraction of with the
organophosphorus mipafox gave rise to a major change in the ion exchange
chromatography profile, but not in the molecular exchanged chromatography
profile, which suggest that mipafox permanently modifies the ionic properties of
numerous proteins.
PMID- 24355588
TI - Transport assays in filamentous fungi: kinetic characterization of the UapC
purine transporter of Aspergillus nidulans.
AB - Transport assays allow the direct kinetic analysis of a specific transporter by
measuring apparent Km and Vmax values, and permit the characterization of
substrate specificity profiles through competition assays. In this protocol we
describe a rapid and easy method for performing uptake assays in the model
filamentous ascomycete Aspergillus nidulans. Our method makes use of A. nidulans
germinating conidiospores at a defined morphological stage in which most
transporters show maximal expression, avoiding technical difficulties associated
with the use of mycelia. In combination with the ease of construction of genetic
null mutants in A. nidulans, our method allows the rigorous characterization of
any transporter in genetic backgrounds that are devoid of other transporters of
similar specificity. Here, we use this method to characterize the kinetic
parameters and the specificity profile of UapC, a uric acid-xanthine transporter
present in all ascomycetes and member of the ubiquitous Nucleobase-Ascorbate
Transporter family, in specific genetic backgrounds lacking other relevant
transporters.
PMID- 24355589
TI - The C-CURE Randomized Clinical Trial (Cardiopoietic stem Cell therapy in heart
failURE).
PMID- 24355591
TI - Reply: The C-CURE Randomized Clinical Trial (Cardiopoietic stem Cell therapy in
heart failURE).
PMID- 24355592
TI - Trends in publication of evidence-based Traditional Iranian medicine in
endocrinology and metabolic disorders.
AB - Traditional Iranian medicine (TIM) is a main part of complementary and
alternative medicine (CAM). The popularity and use of alternative therapies are
increasing due to adverse effects and ineffectiveness of pharmacologic treatments
in some cases. Herbal medicine is one of the methods of traditional therapy that
plays a key role in the treatment of various diseases specifically in diabetes
mellitus, hyperlipidemia and obesity that are growing rapidly in the world. In
this article, trends of scientific publications of Iranian medicine in
endocrinology and metabolic disorders have been investigated. Our data show that
the numbers of related researches have uptrend from 2000 till now. These data are
valuable to pharmaceutical companies to get the idea to invest and produce
effective drugs.
PMID- 24355593
TI - Etiology of sicca syndrome in a consecutive series of 199 patients with chronic
fatigue syndrome.
PMID- 24355594
TI - Hard paracervical tumor in a patient with limited systemic sclerosis.
PMID- 24355595
TI - Case 3--2014: Cor triatriatum sinister presenting in adulthood.
PMID- 24355596
TI - C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading
enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study.
AB - BACKGROUND AND OBJECTIVE: In the last few decades we have witnessed an
interesting transformation of the population pyramids throughout the world. As
the population's life expectancy increases, there are more chronic diseases such
as diabetes mellitus and dementias, and both of them have shown an association.
GENERAL OBJETIVE: To determine the association between Alzheimer's disease in
diabetic patients and the insulin degrading enzyme in outpatients of a second
level Hospital in Monterrey, Mexico. MATERIALS AND METHODS: This was a case
control study in which we included outpatients from the Geriatrics Clinic of a
Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score
Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who
had MMSE scores greater than 24. RESULTS: Data from 97 patients were analyzed.
Regarding physical examination and the results of laboratory tests, there were no
differences between the two groups (p>0.05). A 98% prevalence of the insulin
degrading enzyme was documented in the sample studied. We found an association
between a homozygous status for the CC genotype and Dementia with an estimated
Odds Ratio (OR) of 2.5 (CI 95% 1.6-3.3) on the bivariate test, while, on the
multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3-8.2). CONCLUSIONS:
Evidence shows that cognitive impairment is more frequent among those exposed to
the C allele of the rs2209972 SNP of the insulin degrading enzyme gene.
PMID- 24355598
TI - The molecular link between inefficient GluA2 Q/R site-RNA editing and TDP-43
pathology in motor neurons of sporadic amyotrophic lateral sclerosis patients.
AB - TAR DNA-binding protein (TDP-43) pathology and reduced expression of adenosine
deaminase acting on RNA 2 (ADAR2), which is the RNA editing enzyme responsible
for adenosine-to-inosine conversion at the GluA2 glutamine/arginine (Q/R) site,
concomitantly occur in the same motor neurons of amyotrophic lateral sclerosis
(ALS) patients; this finding suggests a link between these two ALS-specific
molecular abnormalities. AMPA receptors containing Q/R site-unedited GluA2 in
their subunit assembly are Ca(2+)-permeable, and motor neurons lacking ADAR2
undergo slow death in conditional ADAR2 knockout (AR2) mice, which is a
mechanistic ALS model in which the ADAR2 gene is targeted in cholinergic neurons.
Moreover, deficient ADAR2 induced mislocalization of TDP-43 similar to TDP-43
pathology seen in the sporadic ALS patients in the motor neurons of AR2 mice. The
abnormal mislocalization of TDP-43 specifically resulted from activation of the
Ca(2+)-dependent serine protease calpain that specifically cleaved TDP-43 at the
C-terminal region, and generated aggregation-prone N-terminal fragments. Notably,
the N-terminal fragments of TDP-43 lacking the C-terminus were demonstrated in
the brains and spinal cords of ALS patients. Because normalization of either the
Ca(2+)-permeability of AMPA receptors or the calpain activity in the motor
neurons normalized the subcellular localization of TDP-43 in AR2 mice, it is
likely that exaggerated calpain-dependent TDP-43 fragments played a role at least
in the initiation of TDP-43 pathology. Elucidation of the molecular cascade of
neuronal death induced by ADAR2 downregulation could provide a new specific
therapy for sporadic ALS. In this review, we summarized the work from our group
on the role of inefficient GluA2 Q/R site-RNA editing and TDP-43 pathology in
sporadic ALS, and discussed possible effects of inefficient ADAR2-mediated RNA
editing in general.
PMID- 24355597
TI - REEP1 and REEP2 proteins are preferentially expressed in neuronal and neuronal
like exocytotic tissues.
AB - The six members of the Receptor Expression Enhancing Protein (REEP) family were
originally identified based on their ability to enhance heterologous expression
of olfactory receptors and other difficult to express G protein-coupled
receptors. Interestingly, REEP1 mutations have been linked to neurodegenerative
disorders of upper and lower motor neurons, hereditary spastic paraplegia (HSP)
and distal hereditary motor neuropathy type V (dHMN-V). The closely related REEP2
isoform has not demonstrated any such disease linkage. Previous research has
suggested that REEP1 mRNA is ubiquitously expressed in brain, muscle, endocrine,
and multiple other organs, inconsistent with the neurodegenerative phenotype
observed in HSP and dHMN-V. To more fully examine REEP1 expression, we developed
and characterized a new REEP1 monoclonal antibody for both immunoblotting and
immunofluorescent microscopic analysis. Unlike previous RT-PCR studies,
immunoblotting demonstrated that REEP1 protein was not ubiquitous; its expression
was restricted to neuronal tissues (brain, spinal cord) and testes. Gene
expression microarray analysis demonstrated REEP1 and REEP2 mRNA expression in
superior cervical and stellate sympathetic ganglia tissue. Furthermore,
expression of endogenous REEP1 was confirmed in cultured murine sympathetic
ganglion neurons by RT-PCR and immunofluorescent staining, with expression
occurring between Day 4 and Day 8 of culture. Lastly, we demonstrated that REEP2
protein expression was also restricted to neuronal tissues (brain and spinal
cord) and tissues that exhibit neuronal-like exocytosis (testes, pituitary, and
adrenal gland). In addition to sensory tissues, expression of the REEP1/REEP2
subfamily appears to be restricted to neuronal and neuronal-like exocytotic
tissues, consistent with neuronally restricted symptoms of REEP1 genetic
disorders.
PMID- 24355599
TI - Selective distribution and dynamic modulation of miRNAs in the synapse and its
possible role in Alzheimer's Disease.
AB - MicroRNAs (miRNAs) are small non-coding RNAs that control a wide range of
functions in the cell. They act as post-transcriptional gene regulators
throughout in development and in adulthood, although recent evidence suggests
their potential role in the onset and development of various diseases and
neuropathologies. In neurons miRNAs seem to play a key role as regulators of
synaptic function. Synapses are vulnerable structures in neurodegenerative
diseases. In particular, synaptic loss has been described as an early event in
the pathogenesis of Alzheimer's Disease (AD). MicroRNA-mediated gene silencing
represents a candidate event for the repression of specific mRNAs and protein
synthesis that could account for synaptic dysfunction. In this work, we review
the participation of miRNAs in synaptic function and consider their possible role
in synaptic alterations in AD. First we review the biogenesis of miRNAs and their
role as post-transcriptional regulators. Then we discuss recently published data
on the distribution of miRNAs in the brain as well as their role in dynamic
regulation at the synapse. In the second part, we briefly introduce the reader to
AD, focusing on synaptic alterations in the progression of the pathology. Then we
discuss possible implications of miRNAs in the associated synaptic dysfunction.
PMID- 24355601
TI - Daily life impairments associated with self-reported childhood/adolescent
attention-deficit/hyperactivity disorder and experiences of diagnosis and
treatment: results from the European Lifetime Impairment Survey.
AB - The Lifetime Impairment Survey assessed impairment and symptoms of attention
deficit/hyperactivity disorder (ADHD) in children/adolescents from six European
countries. Parents/caregivers of children/adolescents aged<20 years with ADHD
(ADHD group; n = 535) and without ADHD (control group; n=424) participated in an
online survey. History of ADHD diagnosis was self-reported. ADHD and control
groups were compared using impairment and symptom scales; higher scores indicate
greater impairment. Mean (SD) age at ADHD diagnosis was 7.0 (2.8) years,
following consultation of 2.7 (2.6) doctors over 20.4 (23.9) months.
Parents/caregivers (64%; 344/535) reported frustration with some aspect of the
diagnostic procedure; 74% (222/298) were satisfied with their child's current
medication. ADHD had a negative impact on children/adolescents in all aspects of
life investigated. The ADHD group had a higher mean (SD) school impairment score
(2.7 [0.7]) compared with the control group (2.1 [0.7]; P<0.001) and were more
likely to be in the bottom of their class (P<0.001). These data provide insights
into impairments associated with ADHD in childhood/adolescence, and identify
areas for improvement in its management and treatment.
PMID- 24355602
TI - [Pruritic maculopapular rash and diarrhea syndrome in a patient with acute
lymphoblastic leukemia in relapse].
PMID- 24355603
TI - [Water for infant bottles and pathogenic parasites].
PMID- 24355600
TI - Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral
nerve injury.
AB - Pathophysiological responses to peripheral nerve injury include alterations in
the activity, intrinsic membrane properties and excitability of spinal neurons.
The intrinsic excitability of alpha-motoneurons is controlled in part by the
expression, regulation, and distribution of membrane-bound ion channels. Ion
channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium
currents and afterhyperpolarization respectively, are localized in high-density
clusters at specific postsynaptic sites (Deardorff et al., 2013; Muennich and
Fyffe, 2004). Previous work has indicated that Kv2.1 channel clustering and
kinetics are regulated by a variety of stimuli including ischemia, hypoxia,
neuromodulator action and increased activity. Regulation occurs via channel
dephosphorylation leading to both declustering and alterations in channel
kinetics, thus normalizing activity (Misonou et al., 2004; Misonou et al., 2005;
Misonou et al., 2008; Mohapatra et al., 2009; Park et al., 2006). Here we
demonstrate using immunohistochemistry that peripheral nerve injury is also
sufficient to alter the surface distribution of Kv2.1 channels on motoneurons.
The dynamic changes in channel localization include a rapid progressive decline
in cluster size, beginning immediately after axotomy, and reaching maximum within
one week. With reinnervation, the organization and size of Kv2.1 clusters do not
fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully
recover. Moreover, unilateral peripheral nerve injury evokes parallel, but
smaller effects bilaterally. These results suggest that homeostatic regulation of
motoneuron Kv2.1 membrane distribution after axon injury is largely independent
of axon reinnervation.
PMID- 24355604
TI - [Surgical site infections: antibiotic prophylaxis in surgery].
AB - Surgical site infections (SSI) are very common, and represent more than 20% of
all hospital-acquired infections. SSIs are associated with a higher mortality, as
well as to an extended hospital stay and costs, depending on the surgical
procedure and type of SSI. Advances in control practices for these infections
include improvement in operating room ventilation, sterilization methods,
barriers, and surgical techniques, as well as in surgical antimicrobial
prophylaxis. For the latter, the antimicrobial agent should: be active against
the most common pathogens, be administered in an appropriate dosage and in a time
frame to ensure serum and tissue concentrations over the period of potential
contamination, be safe, and be administered over the shortest effective time
period to minimize adverse events, development of resistances, and cost.
PMID- 24355605
TI - First detection and characterization of an OXA-48-producing Enterobacter
aerogenes isolate.
PMID- 24355606
TI - [Sudden onset of distal bullae and splinter hemorraghes].
PMID- 24355607
TI - [Carbapenem antibiotics in hospitalised paediatric patients. Adherence to a
therapeutic protocol].
AB - OBJECTIVE: To describe the use of carbapenems in children hospitalised outside
intensive care and onco-haematology units, and assess adherence to a therapeutic
protocol. PATIENTS AND METHODS: A retrospective observational study was conducted
on the use of carbapenems between January 2009 and December 2010. The study
included children with a community-acquired infectious disease or a health care
associated infectious disease, and who were admitted to paediatric areas of the
Vall d'Hebron University Hospital (Barcelona, Spain), other than intensive care,
neonatology and onco-haematology units. Clinical data were collected and
antibiotic consumption data were provided by the Pharmacy Department. RESULTS: A
total of 51 episodes fulfilled the inclusion criteria. Carbapenem as initial
empirical treatment was indicated in 31.4%, and applied as rescue therapy in the
remainder. The instructions of the protocol were adhered to in 70.6% of the
empirical and 87.5% of the targeted prescriptions (77.6% overall). A better match
was found for empirical carbapenem in patients with a previous admission or
underlying condition. Factors such as diagnosis, age or antibiotic use prior to
admission did not affect the empirical indication of carbapenem. CONCLUSIONS: The
establishment of a treatment protocol with carbapenem indications in our centre
since 2007 has yielded significantly better results on the appropriateness of the
prescription than those obtained in other studies.
PMID- 24355608
TI - Cataplectic attacks during rapid eye movement sleep behavior disorder episodes in
a narcoleptic patient.
PMID- 24355609
TI - Biased competition between Lgr5 intestinal stem cells driven by oncogenic
mutation induces clonal expansion.
AB - The concept of 'field cancerization' describes the clonal expansion of
genetically altered, but morphologically normal cells that predisposes a tissue
to cancer development. Here, we demonstrate that biased stem cell competition in
the mouse small intestine can initiate the expansion of such clones. We
quantitatively analyze how the activation of oncogenic K-ras in individual
Lgr5(+) stem cells accelerates their cell division rate and creates a biased
drift towards crypt clonality. K-ras mutant crypts then clonally expand within
the epithelium through enhanced crypt fission, which distributes the existing
Paneth cell niche over the two new crypts. Thus, an unequal competition between
wild-type and mutant intestinal stem cells initiates a biased drift that leads to
the clonal expansion of crypts carrying oncogenic mutations.
PMID- 24355611
TI - Characteristics of hepatocellular carcinoma with stem/progenitor cell phenotypes.
PMID- 24355610
TI - Brilliant cresyl blue staining negatively affects mitochondrial functions in
porcine oocytes.
AB - The aim of the present study was to examine the effects of brilliant cresyl blue
(BCB) staining on mitochondrial functions in porcine oocytes. Cumulus-oocyte
complexes (COCs) collected from slaughterhouse-derived porcine ovaries were
cultured with (13 MUM) or without (0 MUM, control) BCB for 60 min. Mitochondrial
functions in oocytes were examined immediately after staining or after in vitro
maturation. The BCB-stained oocytes produced reactive oxygen species (ROS) at
higher levels than control oocytes immediately after staining (2.2-fold, P <
0.001) and after maturation (1.7-fold, P < 0.001). The adenosine triphosphate
(ATP) content and mitochondrial membrane potential (MMP) in oocytes were similar
for the two groups immediately after staining. However, ATP and relative MMP
levels were significantly (P < 0.05) lower in BCB-treated oocytes than in the
control (2.18 versus 2.83 pM and 0.82 versus 1.0, respectively). There was no
difference in mitochondrial DNA copy number between the two groups after
maturation. The ATP content in early developmental stage embryos (3 days after
parthenogenetic activation) was lower in the BCB-stained group than that in the
control group but the difference was not significant. In conclusion, BCB staining
of oocytes at the immature stage compromises mitochondrial functions throughout
oocyte maturation, but function is restored during early embryo development.
PMID- 24355612
TI - Dedicated outreach is effective in increasing uptake of colorectal cancer
screening in an underserved population.
PMID- 24355613
TI - Intravenous hydration for the prevention of post-endoscopic retrograde
cholangiopancreatography pancreatitis.
PMID- 24355615
TI - [Endothelial function: role, assessment and limits].
AB - For several years, detecting and preventing cardiovascular diseases have become a
major issue. Different methods have been developed to evaluate endothelial
function. Endothelial dysfunction is one of the first steps leading to
atherosclerosis. This review presents an insight into endothelial function, the
interests of its assessment and methods for studying endothelial function. To
date, the vascular endothelium must be considered as a specific organ with its
own functions that contribute to the homeostasis of the cardiovascular system.
Endothelial dysfunction typically corresponds to a decrease of nitric oxide NO
bioavailability. Biological or physico-chemical methods may be used to assess
dysfunction. Biological methods allow measuring NO metabolites and pro
inflammatory and vasoconstrictor mediators released by the endothelium. The
physico-chemical methods include intra-coronary injections, plethysmography, flow
mediated dilation (FMD), digital plethysmography and optical techniques using
laser (laser Doppler single-point, laser Doppler imager, laser speckle contrast
imaging) that can be coupled with provocation tests (iontophoresis,
microdialysis, post-ischemic hyperemia, local heating). The principle of each
technique and its use in clinical practice are discussed. Studying endothelial
dysfunction is a particularly promising field because of new drugs being
developed. Nevertheless, assessment methodology still needs further development
to enable reliable, non-invasive, reproducible, and inexpensive ways to analyze
endothelial dysfunction.
PMID- 24355614
TI - Effect of socioeconomic disparities on incidence of dementia among biracial older
adults: prospective study.
AB - OBJECTIVE: To examine whether observed differences in dementia rates between
black and white older people living in the community could be explained by
measures of socioeconomic status (income, financial adequacy, education, and
literacy) and health related factors. DESIGN: Prospective cohort study. SETTING:
General community from two clinic sites in the United States (Pittsburgh,
Pennsylvania and Memphis, Tennessee). PARTICIPANTS: 2457 older people (mean age
73.6 years; 1019 (41.5%) black; 1233 (50.2%) women), dementia-free at baseline,
in the Health, Aging, and Body Composition study. MAIN OUTCOME MEASURE: Dementia
was determined over 12 years (ending January 2011) by prescribed dementia drugs,
hospital records, and decline in global cognitive scores. The influence of
socioeconomic status and health related factors on dementia rates was examined in
a series of Cox proportional hazard models in which these variables were added
sequentially in covariate blocks. RESULTS: Over follow-up, 449 (18.3%)
participants developed dementia. Black participants were more likely than white
participants to develop dementia (211 (20.7%) v 238 (16.6%), P<0.001; unadjusted
hazard ratio 1.44, 95% confidence interval 1.20 to 1.74). The hazard ratio
lessened somewhat after adjustment for demographics, apolipoprotein E e4,
comorbidities, and lifestyle factors (1.37, 1.12 to 1.67) but was greatly reduced
and no longer statistically significant when socioeconomic status was added
(1.09, 0.87 to 1.37). CONCLUSION: These findings suggest that differences in the
burden of risk factors, especially socioeconomic status, may contribute to the
higher rates of dementia seen among black compared with white older people.
Strategies aimed at reducing these disparities may favorably affect the incidence
of dementia.
PMID- 24355616
TI - [Traumatic dissection of the innominate artery. A case report].
AB - INTRODUCTION: Lesions affecting the supra-aortic arterial trunks often occur in a
contest of severe chest trauma. They are rarely isolated and can be life
threatening. We report a case of surgery for an isolated traumatic dissection of
the innominate artery. CASE REPORT: A 48-year-old patient had a road accident
causing head injury, trauma of the left lower limb and blunt chest trauma. At the
physical exam, the pulse at the upper right limb was weak compared to the
contralateral member. A pressure gradient of 50mm Hg was recorded between the two
upper limbs. A whole body scan revealed a dissection of the innominate artery
sparing its origin and bifurcation. Cervicotomy and sternotomy was necessary to
achieve control. After heparinization and clamping, a prosthetic bypass was
inserted to replace the innominate artery. The postoperative course was
uneventful and the pressure gradient between the two upper limbs disappeared.
CONCLUSION: Lesions of the brachiocephalic arterial trunk are not frequent but
they are serious. A careful physical exam at admission helps detect them.
Prognosis is directly linked to early diagnosis and management. Conventional
surgery provides good results and remains the standard treatment for these
lesions.
PMID- 24355617
TI - Relation between carotid intima media thickness and oxidative stress markers in
type 1 diabetic children and adolescents.
AB - BACKGROUND: Carotid intima media thickness (CIMT) is a non invasive marker of
subclinical atherosclerosis. Hyperglycemia, oxidatively modified atherogenic
lipoproteins and advanced glycation end products are linked to increased
oxidative stress in diabetes. We aimed to find out the relation between carotid
intima media thickness in type 1 diabetic children and adolescents and plasma
nitric oxide and total antioxidant capacity levels as markers of oxidative
stress. METHODS: This study included 50 children and adolescents with type 1
diabetes mellitus with mean age (9.7 +/- 3.4 years) and 50 healthy age and sex
matched controls. They were subjected to assessment of hemoglobin A1c, total
cholesterol and triglycerides, serum total antioxidant capacity, serum nitric
oxide (NO) by colorimetric method and carotid intima media thickness by B-mode
ultrasound. RESULTS: There was significant elevation in serum nitric oxide (17.07
+/- 6.4 vs 12.6 +/- 4.7 MUmol/L; p < 0.001), CIMT (0.47 +/- 0.04 vs 0.39 +/- 0.02
mm; p < 0.001) and significant reduction in serum total antioxidant capacity
(0.41 +/- 0.29 vs 0.87 +/- 0.23 mmol/L; p < 0.001) in diabetic patients compared
to controls. Carotid intima media thickness was correlated positively with nitric
oxide (r = 0.402, p = 0.01) and negatively with total antioxidant capacity (r =
0.341, p = 0.02). Carotid intima media thickness was also correlated positively
with age, duration of diabetes but not correlated with glycemic control or lipid
profile. CONCLUSION: The significant elevation in nitric oxide and reduction in
total antioxidant capacity in children and adolescents with type 1 diabetes
mellitus with their correlation with carotid intima media thickness may reflect
the role of oxidative stress in the development of atherosclerosis in young type
1 diabetic subjects.
PMID- 24355618
TI - Towards better modeling of chitosan nanoparticles production: screening different
factors and comparing two experimental designs.
AB - The aim of this study is to utilize statistical designs and mathematical modeling
to end the continuous debate about the different variables that influence the
production of nanoparticles using the ionic gelation method between the
biopolymer chitosan (CS) and tripolyphosphate (TPP) ion. Preliminary experiments
were adopted to extract the optimum conditions for the nanoparticles preparation
and model construction. Critical process parameters were screened using the one
factor-at-a-time (OFAT) approach to select optimum experimental regions. Finally,
these factors were optimized using two different methods of response surface
modeling; the Box-Behnken and the D-optimal. The significant models showed
excellent fitting of the data. The two methods were validated using a set of
check points and were subsequently compared. Good agreement between actual and
predicted values was obtained though the D-optimal model was more successful in
predicting the particle size of the prepared nanoparticles with percentage bias
as small as 1.49%. Nanoparticles were produced with diameters ranging from 52.21
nm to 400.30 nm, particle polydispersity from 0.06 to 0.40 and suitable
morphology. This work provides an overview on the production of chitosan
nanoparticles with desirable size enabling their successful use in drugs delivery
and targeting or in any nanotechnology or interfacial application.
PMID- 24355619
TI - Modifying theophylline microparticle surfaces via the sequential deposition of
poly(vinyl alcohol-co-vinyl acetate) copolymers.
AB - The aim of this study was to investigate the manner in which amphiphilic
poly(vinyl alcohol-co-vinyl acetate) copolymers (PVA-Ac) assembled on drug
surfaces and use this information to generate a novel bi-layer polymer coating
for a theophylline microparticle. Three grades of PVA-Ac, differing in hydrolysis
degree and monomer distribution, were synthesised, characterised by nuclear
magnetic resonance and shown to interact with theophylline when suspended in
water. PVA-Ac deposition at the solid/liquid interface was driven by polymer
hydrogen bond formation in a process that induced consequential structural
changes in the macromolecule architecture. The most hydrophobic grades of the
copolymer appeared to adsorb in a multistage process that passed through a series
of equilibrium points. The PVA-Ac surface allowed two grades of the copolymer to
be sequentially adsorbed and this resulted in the fabrication of a microparticle
with desirable characteristics for pharmaceutical formulation production.
PMID- 24355620
TI - Liposome encapsulation of curcumin: physico-chemical characterizations and
effects on MCF7 cancer cell proliferation.
AB - The role of curcumin (diferuloylmethane), for cancer treatment has been an area
of growing interest. However, due to its low absorption, the poor bioavailability
of curcumin limits its clinical use. In this study, we reported an approach of
encapsulation a curcumin by nanoliposome to achieve an improved bioavailability
of a poorly absorbed hydrophobic compound. We demonstrated that liposomal
preparations to deliver curcumin increase its bioavailability. Liposomes composed
of salmon's lecithin also improved curcumin bioavailability compared to those
constituted of rapeseed and soya lecithins. A real-time label-free cell analysis
system based on real-time cell impedance monitoring was used to investigate the
in vitro cytotoxicity of liposomal preparations.
PMID- 24355621
TI - A system for accurate and automated injection of hyperpolarized substrate with
minimal dead time and scalable volumes over a large range.
AB - Over recent years hyperpolarization by dissolution dynamic nuclear polarization
has become an established technique for studying metabolism in vivo in animal
models. Temporal signal plots obtained from the injected metabolite and daughter
products, e.g. pyruvate and lactate, can be fitted to compartmental models to
estimate kinetic rate constants. Modeling and physiological parameter estimation
can be made more robust by consistent and reproducible injections through
automation. An injection system previously developed by us was limited in the
injectable volume to between 0.6 and 2.4ml and injection was delayed due to a
required syringe filling step. An improved MR-compatible injector system has been
developed that measures the pH of injected substrate, uses flow control to reduce
dead volume within the injection cannula and can be operated over a larger volume
range. The delay time to injection has been minimized by removing the syringe
filling step by use of a peristaltic pump. For 100MUl to 10.000ml, the volume
range typically used for mice to rabbits, the average delivered volume was 97.8%
of the demand volume. The standard deviation of delivered volumes was 7MUl for
100MUl and 20MUl for 10.000ml demand volumes (mean S.D. was 9 ul in this range).
In three repeat injections through a fixed 0.96mm O.D. tube the coefficient of
variation for the area under the curve was 2%. For in vivo injections of
hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the
input femoral vein cannula at 3-4s post-injection trigger signal and at 9-12s in
tumor tissue. The pH of the injected pyruvate was 7.1+/-0.3 (mean+/-S.D., n=10).
For small injection volumes, e.g. less than 100MUl, the internal diameter of the
tubing contained within the peristaltic pump could be reduced to improve
accuracy. Larger injection volumes are limited only by the size of the receiving
vessel connected to the pump.
PMID- 24355622
TI - Sensitivity enhancement and contrasting information provided by free radicals in
oriented-sample NMR of bicelle-reconstituted membrane proteins.
AB - Elucidating structure and topology of membrane proteins (MPs) is essential for
unveiling functionality of these important biological constituents. Oriented
sample solid-state NMR (OS-NMR) is capable of providing such information on MPs
under nearly physiological conditions. However, two dimensional OS-NMR
experiments can take several days to complete due to long longitudinal relaxation
times combined with the large number of scans to achieve sufficient signal
sensitivity in biological samples. Here, free radicals 5-DOXYL stearic acid,
TEMPOL, and CAT-1 were added to uniformly (15)N-labeled Pf1 coat protein
reconstituted in DMPC/DHPC bicelles, and their effect on the longitudinal
relaxation times (T1Z) was investigated. The dramatically shortened T1Z's allowed
for the signal gain per unit time to be used for either: (i) up to a threefold
reduction of the total experimental time at 99% magnetization recovery or (ii)
obtaining up to 74% signal enhancement between the control and radical samples
during constant experimental time at "optimal" relaxation delays. In addition,
through OS-NMR and high-field EPR studies, free radicals were able to provide
positional constraints in the bicelle system, which provide a description of the
location of each residue in Pf1 coat protein within the bicellar membranes. This
information can be useful in the determination of oligomerization states and
immersion depths of larger membrane proteins.
PMID- 24355623
TI - Effects of a metabolic syndrome induced by a fructose-rich diet on bone
metabolism in rats.
AB - OBJECTIVE: The aims of this study were: first, to evaluate the possible effects
of a fructose rich diet (FRD)-induced metabolic syndrome (MS) on different
aspects of long bone histomorphometry in young male rats; second, to investigate
the effects of this diet on bone tissue regeneration; and third, to correlate
these morphometric alterations with changes in the osteogenic/adipogenic
potential and expression of specific transcription factors, of marrow stromal
cells (MSC) isolated from rats with fructose-induced MS. MATERIALS/METHODS: MS
was induced in rats by treatment with a FRD for 28 days. Halfway through
treatment, a parietal wound was made and bone healing was evaluated 14 days
later. After treatments, histomorphometric analysis was performed in dissected
femoral and parietal bones. MSC were isolated from the femora of control or
fructose-treated rats and differentiated either to osteoblasts (evaluated by type
1 collagen, Alkaline phosphatase and extracellular nodule mineralization) or to
adipocytes (evaluated by intracellular triglyceride accumulation). Expression of
Runx2 and PPARgamma was assessed by Western blot. RESULTS: Fructose-induced MS
induced deleterious effects on femoral metaphysis microarchitecture and impaired
bone regeneration. Fructose treatment decreased the osteogenic potential of MSC
and Runx2 expression. In addition, it increased the adipogenic commitment of MSC
and PPARgamma expression. CONCLUSIONS: Fructose-induced MS is associated with
deleterious effects on bone microarchitecture and with a decrease in bone repair.
These alterations could be due to a deviation in the adipogenic/osteogenic
commitment of MSC, probably by modulation of the Runx2/PPARgamma ratio.
PMID- 24355624
TI - Bone metabolism in obese rats programmed by early weaning.
AB - OBJECTIVE: Obesity and osteoporosis seem to have a common pathogenesis,
especially because bone and adipose tissue have common origins. Since early
weaning (EW) decreases adipogenesis and osteogenesis in neonate, further
programming for obesity and hyperleptinemia, we hypothesized that these changes
in adipogenesis could affect bone metabolism. MATERIALS/METHODS: Lactating rats
were separated into 3 groups: control - dams whose pups ate milk throughout
lactation; mechanical EW (MEW) - dams were involved with a bandage interrupting
suckling in the last 3days of lactation; pharmacological EW (PEW) - dams were
bromocriptine-treated (0.5mg/twice a day via intraperitoneal injection) 3days
before weaning. The adult offspring was subjected to dual-energy X-ray
absorptiometry and bone tissue was also evaluated by computed tomography,
microcomputed tomography and biomechanical tests, beyond serum analyses. RESULTS:
MEW and PEW presented higher total bone mineral density (BMD), total bone mineral
content, spine BMD and bone area in postnatal day 150 (PN150). In PN180, both
groups also presented increase of these parameters and higher femur BMD and
fourth lumbar vertebra (LV4) BMD, femoral head radiodensity and LV4 vertebral
body radiodensity, trabecular number, stiffness and break load; lower trabecular
separation, maximal deformation and break deformation, and also hyperleptinemia
and higher visceral fat mass and 25-hydroxivitamin D, whereas parathyroid hormone
was unchanged. Serum C-terminal cross-linked telopeptide of type I collagen was
lower for both groups. CONCLUSIONS: Since both models program for obesity and
increased bone mass, and leptin increases plasma vitamin D levels, probably
leptin is the link between obesity and higher bone mass.
PMID- 24355625
TI - Effects of exercise on C-reactive protein, inflammatory cytokine and adipokine in
patients with type 2 diabetes: a meta-analysis of randomized controlled trials.
AB - OBJECTIVE: C-reactive protein (CRP), inflammatory cytokines, and adipokines
contribute to atherosclerosis, insulin resistance, and development of late-onset
complication in patients with type 2 diabetes. We performed a systematic review
to assess effects of exercise interventions on inflammatory markers/cytokines and
adipokines. MATERIALS/METHODS: We searched electronic databases (MEDLINE, EMBASE,
and Cochrane Controlled Trials Registry) and reference lists in relevant papers
for articles published in 1966-2013. We selected studies that evaluated the
effects of exercise intervention on inflammatory markers/cytokines and adipokines
in adult patients with type 2 diabetes. Weighted mean differences of exercise on
outcomes were derived using fixed or random effect models; factors influencing
heterogeneity were identified using meta-regression analysis. RESULTS: Fourteen
randomized controlled trials (824 patients) were included in our meta-analysis.
Exercise was associated with a significant in CRP=-0.66mg/l (95% CI, -1.09 to
0.23mg/l; -14% from baseline) and interleukin-6 (IL-6)=-0.88pg/ml (95% CI, -1.44
to -0.32pg/ml; -18% from baseline) but did not alter adiponectin or resistin
levels; aerobic exercise program was associated with a significant change in
leptin=-3.72ng/ml (95% CI, -6.26 to -1.18ng/ml; -24% from baseline). For IL-6,
exercise was more effective in those with a longer duration in the program and
larger number of sessions during study (p=0.001). CONCLUSIONS: Exercise decreases
inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise
could be a therapeutic option for improving abnormalities in inflammation levels
in patients with diabetes.
PMID- 24355626
TI - How does support from peers compare with support from adults as students
transition to secondary school?
AB - PURPOSE: Understanding how young people navigate the transition from primary to
secondary school is critical for preventing the adverse mental health, social,
and academic outcomes associated with a difficult transition. This study sought
to determine from whom young people receive support before the transition period
to help inform the development of future intervention research testing, as well
as peer, school, and family-based supports during transition. METHODS: Data were
collected from 1,974 primary school students prior to the transition and again in
Term 1 of the first year of secondary school. Students were asked about their
expectation of the transition as well as their support from peers, family, and
the school. Just over half (52%) of the sample were females with a mean age of 12
years. RESULTS: Peer, school, and family supports all predicted positive student
transition experiences. When in Grade 7 and considering all predictors together,
a high level of perceived peer support was the most significant predictor of an
expectation of an easy or somewhat easy transition. In Grade 8, again after
considering all sources of support, parental presence was the most significant
protective predictor of an easy or somewhat easy transition experience.
CONCLUSIONS: Students who expect and experience a positive transition to
secondary school are generally well-supported by their peers, school, and family.
The most stable influence for young people over the transition period is the
presence of families before and after school and future intervention efforts to
support young people during transition need to build support from families.
PMID- 24355627
TI - Factors influencing abstinence, anticipation, and delay of sex among adolescent
boys in high-sexually transmitted infection prevalence communities.
AB - PURPOSE: Abstinence is a core pregnancy and sexually transmitted infection (STI)
prevention strategy. We explore the attitudinal, behavioral, and family contexts
relating to abstinence and the decision to delay sex among adolescent boys.
METHODS: Adolescent boys ages 14-17 years were recruited from community sites
using a venue-based sampling method. All eligible boys at venues were invited to
participate in an electronic survey. Question items included sexual behaviors,
attitudes related to sex, relationships, masculine values, and family contextual
items. RESULTS: We enrolled 667 participants, mean age 15.7 years, of diverse
ethnicity. A total of 252 were abstinent (38%). Abstinent participants were
younger and less likely to report non-coital behaviors, and reported lower
conventional masculine values. Among abstinent participants, 62% planned to delay
sex, whereas 38% anticipated sex in the next year. Participants with lower
conventional masculine values and more religious or moral motivations for
abstinence were more likely to plan to delay sex. CONCLUSIONS: Abstinence among
boys is common, even in high-STI risk communities. For these boys, abstinence
appears to be a complex behavioral decision influenced by demographic,
behavioral, attitudinal, and contextual factors such as age, race, non-coital
sexual behaviors, and masculine values. Understanding the attitudes and contexts
of abstinence, including plans to delay sex, can inform the development of public
health programs for early fatherhood and STI prevention.
PMID- 24355628
TI - Prevalence of diagnosed depression in adolescents with history of concussion.
AB - PURPOSE: Previous studies in adults have suggested concussion and other brain
injury presents a risk factor for depression. The goal of our study was to
analyze the association between previous concussion and current depression
diagnosis in a large nationally representative adolescent data set. METHODS:
Retrospective cohort study using the National Survey of Children's Health 2007
2008, a nationally representative survey conducted via random digit dialing. Data
were obtained by parental report. We included youth 12-17 years old without a
current concussion (N = 36,060), and evaluated the association between previous
concussion (binary) and current depression diagnosis (binary) using multiple
logistic regression to control for age, sex, parental mental health, and
socioeconomic status. RESULTS: After controlling for age, sex, parental mental
health, and socioeconomic status, history of concussion was associated with a 3.3
fold greater risk for depression diagnosis (95% CI: 2.0-5.5). Other factors
significantly associated with depression diagnosis included poor or fair parental
mental health (OR: 3.7, 95% CI: 2.8-4.9), and older age (15-17 years vs. 12-14
years, OR: 1.4, 95% CI: 1.1-1.8). Sex of the subject was not significantly
related to depression diagnosis. Being above 200% of the poverty level was
associated with approximately a 50% decreased risk of depression diagnosis (95%
CI: 35%-70%). CONCLUSIONS: History of concussion was associated with a higher
prevalence of diagnosed depression in a large nationally representative
adolescent data set. Clinicians should screen for depression in their adolescent
patients with concussion. Future studies should confirm this association using
prospective methodology and examine potential treatment approaches.
PMID- 24355629
TI - Prevalence and clinical characteristics of chronic venous disease in patients
seen in primary care in Spain: results of the international study Vein Consult
Program.
AB - INTRODUCTION: The aim of this study was to evaluate the prevalence, clinical
characteristics and management of chronic venous disease (CVD) in patients seen
at primary care clinics PATIENTS AND METHODS: This cross-sectional study was
carried-out in Spain by 999 primary care physicians. They recruited 20
consecutive patients who were attending their clinics for any reason except for a
medical emergency. The following Information was collected: demographic data, CVD
risk factors, physical examination, clinical characteristics of the CVD and how
it was managed. RESULTS: 19,800 patients were included, predominantly women
(63%), with a mean age of 53.7 +/- 20 years. The prevalence of CVD (CEAP
categories C1 to C6) was 48.5% (95% CI, 47.8 to 49.2), significantly higher in
women (58.5%; 95% CI, 57.6 to 59.4) than in men (32.1%; 95% CI, 31.0 to 33.1).
The greater the age the higher the prevalence and the more advanced the CVD.
Ninety-nine percent of the patients required some form of treatment, with a
greater proportion among women (72% vs. 39%, P<.0001). Sclerotherapy, endothermal
ablation or surgery was required by 4% of the patients. Referral to the
specialist was considered for 7% of the patients. CONCLUSION: Chronic venous
disease is highly prevalent among patients seen at primary care clinics in Spain,
especially in women and elderly patients. Referral to a specialist and/or the use
of the more invasive treatment procedures is uncommon.
PMID- 24355630
TI - Mixed Choledochal Cyst (type I and II) Associated With a Malformation of the
Pancreatobiliary Junction. A Case Report and Review of the Literature.
PMID- 24355631
TI - Heparin-derived supersulfated disaccharide inhibits allergic airway responses in
sheep.
AB - The tetrasaccharide sequence of heparin oligosaccharides is the minimum chain
length possessing anti-allergic activity, as the disaccharide fraction is
inactive. Since sulfation pattern can modify the biological actions of heparin,
we hypothesized that "supersulfation" of the inactive heparin disaccharide could
confer anti-allergic activity to this molecule. To test this, we produced a
supersulfated heparin disaccharide (Hep-SSD) and evaluated its anti-allergic
activity in sheep with documented antigen-induced early and late airway responses
(EAR and LAR) and airway hyperresponsiveness (AHR). Porcine intestinal heparin
was depolymerized with nitrous acid, the disaccharide fraction separated by size
exclusion chromatography, and then treated with pyridine-sulfur trioxide complex
to yield Hep-SSD. Its chemical structure [IdoU2',3',4'S (1->4) AMan1,3,6S] was
confirmed by HPLC, Mass Spectrometry and NMR analysis. Inhaled doses of 5 mg, 10
mg and 20 mg Hep-SSD produced inhibition of EAR (8%, 35% and 35%), LAR (50%, 80%,
and 77%) and AHR (67%, 100% and 75%), respectively. A single oral dose of 2 mg/kg
Hep-SSD given 90 min before challenge significantly inhibited EAR, LAR and AHR,
but 1 mg/kg was ineffective. Multi dose oral treatment with Hep-SSD had a
cumulative effect, as a once daily dose of 2 mg/kg for 3 days (last dose, 16 h
before antigen) inhibited EAR, LAR and AHR by 30%, 75% and 74%, respectively.
Finally, the oral activity of Hep-SSD could be enhanced 4 fold by formulating it
with Carbopol((r))934P, in an enteric coated capsule. These data demonstrate that
"supersulfation" can confer biological activity to the inactive heparin
disaccharide. Both inhaled and oral Hep-SSD demonstrate significant anti-allergic
activity and, therefore, may have therapeutic potential.
PMID- 24355632
TI - The number processing and calculation system: evidence from cognitive
neuropsychology.
AB - INTRODUCTION: Cognitive neuropsychology focuses on the concepts of dissociation
and double dissociation. The performance of number processing and calculation
tasks by patients with acquired brain injury can be used to characterise the way
in which the healthy cognitive system manipulates number symbols and quantities.
The objective of this study is to determine the components of the numerical
processing and calculation system. METHODS: Participants consisted of 6 patients
with acquired brain injuries in different cerebral localisations. We used Bateria
de evaluacion del procesamiento numerico y el calculo, a battery assessing number
processing and calculation. Data was analysed using the difference in proportions
test. RESULTS: Quantitative numerical knowledge is independent from number
transcoding, qualitative numerical knowledge, and calculation. Recodification is
independent from qualitative numerical knowledge and calculation. Quantitative
numerical knowledge and calculation are also independent functions. CONCLUSIONS:
The number processing and calculation system comprises at least 4 components that
operate independently: quantitative numerical knowledge, number transcoding,
qualitative numerical knowledge, and calculation. Therefore, each one may be
damaged selectively without affecting the functioning of another. According to
the main models of number processing and calculation, each component has
different characteristics and cerebral localisations.
PMID- 24355633
TI - The Fifth World Symposium on Pulmonary Hypertension.
PMID- 24355634
TI - Pulmonary hypertension due to left heart diseases.
AB - Pulmonary hypertension (PH), a common complication of left heart diseases (LHD),
negatively impacts symptoms, exercise capacity, and outcome. Although the true
prevalence of PH-LHD is unknown, a subset of patients might present significant
PH that cannot be explained by a passive increase in left-sided filling
pressures. The term "out-of-proportion" PH has been used to identify that
population without a clear definition, which has been found less than ideal and
created confusion. We propose a change in terminology and a new definition of PH
due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish
"isolated post-capillary PH" from "post-capillary PH with a pre-capillary
component" on the basis of the pressure difference between diastolic pulmonary
artery pressure and pulmonary artery wedge pressure. Although there is no
validated treatment for PH-LHD, we provide insights into management and discuss
completed and randomized trials in this condition. Finally, we provide
recommendations for future clinical trials to establish safety and efficacy of
novel compounds to target this area of unmet medical need.
PMID- 24355635
TI - Pulmonary hypertension in chronic lung diseases.
AB - Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases
(DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are
associated with a high incidence of pulmonary hypertension (PH), which is linked
with exercise limitation and a worse prognosis. Patients with combined pulmonary
fibrosis and emphysema (CPFE) are particularly prone to the development of PH.
Echocardiography and right heart catheterization are the principal modalities for
the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients
with concomitant respiratory abnormalities and group 3 PH patients (PH caused by
lung disease), patients should be transferred to a center with expertise in both
PH and lung diseases for comprehensive evaluation. The task force encompassing
the authors of this article provided criteria for this discrimination and
suggested using the following definitions for group 3 patients, as exemplified
for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure
[mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP >=25 mm Hg); PH-COPD, PH-IPF, and
PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP >=35 mm Hg or mPAP >=25 mm Hg with
low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe
PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease
patients who are suspected of having strong general vascular abnormalities
(remodeling) accompanying the parenchymal disease and with evidence of an
exhausted circulatory reserve rather than an exhausted ventilatory reserve
underlying the limitation of exercise capacity. Exertional dyspnea
disproportionate to pulmonary function tests, low carbon monoxide diffusion
capacity, and rapid decline of arterial oxygenation upon exercise are typical
clinical features of this subgroup with poor prognosis. Studies evaluating the
effect of pulmonary arterial hypertension drugs currently not approved for group
3 PH patients should focus on this severe PH group, and for the time being, these
patients should be transferred to expert centers for individualized patient care.
PMID- 24355636
TI - Pediatric pulmonary hypertension.
AB - Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children
that is associated with significant morbidity and mortality. In the majority of
pediatric patients, PH is idiopathic or associated with congenital heart disease
and rarely is associated with other conditions such as connective tissue or
thromboembolic disease. Incidence data from the Netherlands has revealed an
annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary
arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension,
respectively, associated with congenital heart disease (CHD) cases per million
children. The updated Nice classification for PH has been enhanced to include a
greater depth of CHD and emphasizes persistent PH of the newborn and
developmental lung diseases, such as bronchopulmonary dysplasia and congenital
diaphragmatic hernia. The management of pediatric PH remains challenging because
treatment decisions continue to depend largely on results from evidence-based
adult studies and the clinical experience of pediatric experts.
PMID- 24355637
TI - Genetics and genomics of pulmonary arterial hypertension.
AB - Major discoveries have been obtained within the last decade in the field of
hereditary predisposition to pulmonary arterial hypertension (PAH). Among them,
the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the
major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1,
also known as ALK1) as the major gene when PAH is associated with hereditary
hemorrhagic telangiectasia. The mutation detection rate for the known genes is
approximately 75% in familial PAH, but the mutation shortfall remains unexplained
even after careful molecular investigation of these genes. To identify additional
genetic variants predisposing to PAH, investigators harnessed the power of next
generation sequencing to successfully identify additional genes that will be
described in this report. Furthermore, common genetic predisposing factors for
PAH can be identified by genome-wide association studies and are detailed in this
paper. The careful study of families and routine genetic diagnosis facilitated
natural history studies based on large registries of PAH patients to be set up in
different countries. These longitudinal or cross-sectional studies permitted the
clinical characterization of PAH in mutation carriers to be accurately described.
The availability of molecular genetic diagnosis has opened up a new field for
patient care, including genetic counseling for a severe disease, taking into
account that the major predisposing gene has a highly variable penetrance between
families. Molecular information can be drawn from the genomic study of affected
tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain
insight into the mechanisms leading to the development of the disease. High
throughput genomic techniques, on the basis of next-generation sequencing, now
allow the accurate quantification and analysis of ribonucleic acid, species,
including micro-ribonucleic acids, and allow for a genome-wide investigation of
epigenetic or regulatory mechanisms, which include deoxyribonucleic acid
methylation, histone methylation, and acetylation, or transcription factor
binding.
PMID- 24355638
TI - Right heart adaptation to pulmonary arterial hypertension: physiology and
pathobiology.
AB - Survival in patients with pulmonary arterial hypertension (PAH) is closely
related to right ventricular (RV) function. Although pulmonary load is an
important determinant of RV systolic function in PAH, there remains a significant
variability in RV adaptation to pulmonary hypertension. In this report, the
authors discuss the emerging concepts of right heart pathobiology in PAH. More
specifically, the discussion focuses on the following questions. 1) How is right
heart failure syndrome best defined? 2) What are the underlying molecular
mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and
function and their prognostic implications best assessed? 4) What is the role of
targeted RV therapy? Throughout the report, the authors highlight differences
between right and left heart failure and outline key areas of future
investigation.
PMID- 24355639
TI - Updated clinical classification of pulmonary hypertension.
AB - In 1998, a clinical classification of pulmonary hypertension (PH) was
established, categorizing PH into groups which share similar pathological and
hemodynamic characteristics and therapeutic approaches. During the 5th World
Symposium held in Nice, France, in 2013, the consensus was reached to maintain
the general scheme of previous clinical classifications. However, modifications
and updates especially for Group 1 patients (pulmonary arterial hypertension
[PAH]) were proposed. The main change was to withdraw persistent pulmonary
hypertension of the newborn (PPHN) from Group 1 because this entity carries more
differences than similarities with other PAH subgroups. In the current
classification, PPHN is now designated number 1. Pulmonary hypertension
associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group
5, unclear/multifactorial mechanism. In addition, it was decided to add specific
items related to pediatric pulmonary hypertension in order to create a
comprehensive, common classification for both adults and children. Therefore,
congenital or acquired left-heart inflow/outflow obstructive lesions and
congenital cardiomyopathies have been added to Group 2, and segmental pulmonary
hypertension has been added to Group 5. Last, there were no changes for Groups 2,
3, and 4.
PMID- 24355640
TI - Relevant issues in the pathology and pathobiology of pulmonary hypertension.
AB - Knowledge of the pathobiology of pulmonary hypertension (PH) continues to
accelerate. However, fundamental gaps remain in our understanding of the
underlying pathological changes in pulmonary arteries and veins in the different
forms of this syndrome. Although PH primarily affects the arteries, venous
disease is increasingly recognized as an important entity. Moreover, prognosis in
PH is determined largely by the status of the right ventricle, rather than the
levels of pulmonary artery pressures. It is increasingly clear that although
vasospasm plays a role, PH is an obstructive lung panvasculopathy. Disordered
metabolism and mitochondrial structure, inflammation, and dysregulation of growth
factors lead to a proliferative, apoptosis-resistant state. These abnormalities
may be acquired, genetically mediated as a result of mutations in bone
morphogenetic protein receptor-2 or activin-like kinase-1, or epigenetically
inherited (as a result of epigenetic silencing of genes such as superoxide
dismutase-2). There is a pressing need to better understand how the pathobiology
leads to severe disease in some patients versus mild PH in others. Recent
recognition of a potential role of acquired abnormalities of mitochondrial
metabolism in the right ventricular myocytes and pulmonary vascular cells
suggests new therapeutic approaches, diagnostic modalities, and biomarkers.
Finally, dissection of the role of pulmonary inflammation in the initiation and
promotion of PH has revealed a complex yet fascinating interplay with pulmonary
vascular remodeling, promising to lead to novel therapeutics and diagnostics.
Emerging concepts are also relevant to the pathobiology of PH, including a role
for bone marrow and circulating progenitor cells and microribonucleic acids.
Continued interest in the interface of the genetic basis of PH and cellular and
molecular pathogenetic links should further expand our understanding of the
disease.
PMID- 24355641
TI - Definitions and diagnosis of pulmonary hypertension.
AB - Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure >= 25
mm Hg at rest, measured during right heart catheterization. There is still
insufficient evidence to add an exercise criterion to this definition. The term
pulmonary arterial hypertension (PAH) describes a subpopulation of patients with
PH characterized hemodynamically by the presence of pre-capillary PH including an
end-expiratory pulmonary artery wedge pressure (PAWP) <= 15 mm Hg and a pulmonary
vascular resistance >3 Wood units. Right heart catheterization remains essential
for a diagnosis of PH or PAH. This procedure requires further standardization,
including uniformity of the pressure transducer zero level at the midthoracic
line, which is at the level of the left atrium. One of the most common problems
in the diagnostic workup of patients with PH is the distinction between PAH and
PH due to left heart failure with preserved ejection fraction (HFpEF). A normal
PAWP does not rule out the presence of HFpEF. Volume or exercise challenge during
right heart catheterization may be useful to unmask the presence of left heart
disease, but both tools require further evaluation before their use in general
practice can be recommended. Early diagnosis of PAH remains difficult, and
screening programs in asymptomatic patients are feasible only in high-risk
populations, particularly in patients with systemic sclerosis, for whom recent
data suggest that a combination of clinical assessment and pulmonary function
testing including diffusion capacity for carbon monoxide, biomarkers, and
echocardiography has a higher predictive value than echocardiography alone.
PMID- 24355642
TI - Pulmonary arterial hypertension: epidemiology and registries.
AB - Registries of patients with pulmonary arterial hypertension (PAH) have been
instrumental in characterizing the presentation and natural history of the
disease and provide a basis for prognostication. Since the initial accumulation
of data conducted in the 1980s, subsequent registry databases have yielded
information about the demographic factors, treatment, and survival of patients
and have permitted comparisons between populations in different eras and
environments. Inclusion of patients with all subtypes of PAH has also allowed
comparisons of these subpopulations. We describe herein the basic methodology by
which PAH registries have been conducted, review key insights provided by
registries, summarize issues related to interpretation and comparison of the
results, and discuss the utility of data to predict survival outcomes. Potential
sources of bias, particularly related to the inclusion of incident and/or
prevalent patients and missing data, are addressed. A fundamental observation of
current registries is that survival in the modern treatment era has improved
compared with that observed previously and that outcomes among PAH subpopulations
vary substantially. Continuing systematic clinical surveillance of PAH will be
important as treatment evolves and as understanding of mechanisms advance.
Considerations for future directions of registry studies include enrollment of a
broader population of patients with pulmonary hypertension of all clinical types
and severity and continued globalization and collaboration of registry databases.
PMID- 24355643
TI - Updated treatment algorithm of pulmonary arterial hypertension.
AB - The demands on a pulmonary arterial hypertension (PAH) treatment algorithm are
multiple and in some ways conflicting. The treatment algorithm usually includes
different types of recommendations with varying degrees of scientific evidence.
In addition, the algorithm is required to be comprehensive but not too complex,
informative yet simple and straightforward. The type of information in the
treatment algorithm are heterogeneous including clinical, hemodynamic, medical,
interventional, pharmacological and regulatory recommendations. Stakeholders (or
users) including physicians from various specialties and with variable expertise
in PAH, nurses, patients and patients' associations, healthcare providers,
regulatory agencies and industry are often interested in the PAH treatment
algorithm for different reasons. These are the considerable challenges faced when
proposing appropriate updates to the current evidence-based treatment
algorithm.The current treatment algorithm may be divided into 3 main areas: 1)
general measures, supportive therapy, referral strategy, acute vasoreactivity
testing and chronic treatment with calcium channel blockers; 2) initial therapy
with approved PAH drugs; and 3) clinical response to the initial therapy,
combination therapy, balloon atrial septostomy, and lung transplantation. All
three sections will be revisited highlighting information newly available in the
past 5 years and proposing updates where appropriate. The European Society of
Cardiology grades of recommendation and levels of evidence will be adopted to
rank the proposed treatments.
PMID- 24355644
TI - Treatment goals of pulmonary hypertension.
AB - With significant therapeutic advances in the field of pulmonary arterial
hypertension, the need to identify clinically relevant treatment goals that
correlate with long-term outcome has emerged as 1 of the most critical tasks.
Current goals include achieving modified New York Heart Association functional
class I or II, 6-min walk distance >380 m, normalization of right ventricular
size and function on echocardiograph, a decreasing or normalization of B-type
natriuretic peptide (BNP), and hemodynamics with right atrial pressure <8 mm Hg
and cardiac index >2.5 mg/kg/min(2). However, to more effectively prognosticate
in the current era of complex treatments, it is becoming clear that the "bar"
needs to be set higher, with more robust and clearer delineations aimed at
parameters that correlate with long-term outcome; namely, exercise capacity and
right heart function. Specifically, tests that accurately and noninvasively
determine right ventricular function, such as cardiac magnetic resonance imaging
and BNP/N-terminal pro-B-type natriuretic peptide, are emerging as promising
indicators to serve as baseline predictors and treatment targets. Furthermore,
studies focusing on outcomes have shown that no single test can reliably serve as
a long-term prognostic marker and that composite treatment goals are more
predictive of long-term outcome. It has been proposed that treatment goals be
revised to include the following: modified New York Heart Association functional
class I or II, 6-min walk distance >= 380 to 440 m, cardiopulmonary exercise test
measured peak oxygen consumption >15 ml/min/kg and ventilatory equivalent for
carbon dioxide <45 l/min/l/min, BNP level toward "normal," echocardiograph and/or
cardiac magnetic resonance imaging demonstrating normal/near-normal right
ventricular size and function, and hemodynamics showing normalization of right
ventricular function with right atrial pressure <8 mm Hg and cardiac index >2.5
to 3.0 l/min/m(2).
PMID- 24355646
TI - Chronic thromboembolic pulmonary hypertension.
AB - Since the last World Symposium on Pulmonary Hypertension in 2008, we have
witnessed numerous and exciting developments in chronic thromboembolic pulmonary
hypertension (CTEPH). Emerging clinical data and advances in technology have led
to reinforcing and updated guidance on diagnostic approaches to pulmonary
hypertension, guidelines that we hope will lead to better recognition and more
timely diagnosis of CTEPH. We have new data on treatment practices across
international boundaries as well as long-term outcomes for CTEPH patients treated
with or without pulmonary endarterectomy. Furthermore, we have expanded data on
alternative treatment options for select CTEPH patients, including data from
multiple clinical trials of medical therapy, including 1 recent pivotal trial,
and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have
garnered more experience, and on a larger international scale, with pulmonary
endarterectomy, which is the treatment of choice for operable CTEPH. This report
overviews and highlights these important interval developments as deliberated
among our task force of CTEPH experts and presented at the 2013 World Symposium
on Pulmonary Hypertension in Nice, France.
PMID- 24355645
TI - New trial designs and potential therapies for pulmonary artery hypertension.
AB - A greater understanding of the epidemiology, pathogenesis, and pathophysiology of
pulmonary artery hypertension (PAH) has led to significant advances, but the
disease remains fatal. Treatment options are neither universally available nor
always effective, underscoring the need for development of novel therapies and
therapeutic strategies. Clinical trials to date have provided evidence of
efficacy, but were limited in evaluating the scope and duration of treatment
effects. Numerous potential targets in varied stages of drug development exist,
in addition to novel uses of familiar therapies. The pursuit of gene and cell
based therapy continues, and device use to help acute deterioration and chronic
management is emerging. This rapid surge of drug development has led to
multicenter pivotal clinical trials and has resulted in novel ethical and global
clinical trial concerns. This paper will provide an overview of the opportunities
and challenges that await the development of novel treatments for PAH.
PMID- 24355647
TI - Depression, subthreshold depression and comorbid anxiety symptoms in older
Europeans: results from the EURODEP concerted action.
AB - BACKGROUND: In the epidemiology of late life depression, few insights are
available on the co-occurrence of subthreshold depression and comorbid symptoms
of anxiety. The current study aims to describe prevalence patterns of comorbid
anxiety symptoms across different levels of depression in old age, and to
describe the burden of depressive symptoms and functional disability across
patterns of comorbidity. METHODS: Respondents were older adults in the community,
age 65-104 (N=14,200), from seven European countries, with in total nine study
centres, collaborating in the EURODEP concerted action. Depression and anxiety
were assessed using the Geriatric Mental State examination (GMS-AGECAT package),
providing subthreshold level and case-level diagnoses. Presence of anxiety
symptoms was defined as at least three distinct symptoms of anxiety. Number of
depressive symptoms was assessed with the EURO-D scale. RESULTS: The prevalence
of anxiety symptoms amounts to 32% for respondents without depression, 67% for
those with subthreshold depression, and 87% for those with case-level depression.
The number of depressive symptoms is similar for those with subthreshold-level
depression with comorbid anxiety, compared to case-level depression without
symptoms of anxiety. In turn, at case level, comorbid symptoms of anxiety are
associated with higher levels of depressive symptoms and more functional
disability. LIMITATIONS: GMS-AGECAT is insufficiently equipped with diagnostic
procedures to identify specific types of anxiety disorders. CONCLUSIONS: Anxiety
symptoms in late life depression are highly prevalent, and are likely to
contribute to the burden of symptoms of the depression, even at subthreshold
level.
PMID- 24355648
TI - Maintenance electroconvulsive therapy up to 12 years.
AB - BACKGROUND: Maintenance electroconvulsive therapy (m-ECT) is effective in
preventing recurrences of depressive episodes. There is little information on
long-term m-ECT extending over several years and its impact on cognitive
functions. This study was an attempt to determine the efficacy and side effects
of long-term m-ECT. METHOD: Depressive episodes and admissions before m-ECT for a
period equal to the duration of m-ECT and during m-ECT were compared using
medical records. Cognitive functions assessed by Mini-Mental State Examination
(MMSE) before and after m-ECT were compared along with the review of
Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). RESULTS: 17 patients had
m-ECT that extended from 6 to 153 months (mean 39, SD=44.46). The average number
of episodes before and during m-ECT was 2.47 (SD=2.23) and 0.88 (SD=1.31)
respectively (Wilcoxon ranked test Z=3.06, r=0.55, two-tailed p=0.002). Average
number of admissions dropped from 2.05 (SD=1.88) to 0.23 (SD=0.43) during m-ECT
(Z=3.471, r=0.71, p=0.001). The average time to recurrence was 24.24 months
(SD=25.20) with longest depression free survival of 105 months. There was no
significant difference in MMSE score before and after the commencement m-ECT or
progressive deterioration in NUCOG score. LIMITATIONS: This study was limited by
retrospective nature of data collection, small sample size, confounding effects
of antidepressants along with m-ECT and absence of a highly sensitive cognitive
screening tool that can capture all types of cognitive impairments following m
ECT. CONCLUSIONS: In a naturalistic setting the efficacy of m-ECT may extend over
several years while cognitive functions remain largely unaffected.
PMID- 24355649
TI - The impact of indiscriminate media coverage of a celebrity suicide on a society
with a high suicide rate: epidemiological findings on copycat suicides from South
Korea.
AB - BACKGROUND: This study examines the extent to which the indiscriminate media
coverage of the famous young actress Lee Eun-ju's suicide in 2005 affected
suicides overall and in specific subgroups (by age, gender, and suicide method)
in a suicide-prone society, South Korea. METHODS: South Korea's 2003-2005 suicide
data (n=34,237) were obtained from death certificate records of the National
Statistical Office (NSO). Data was analyzed with Poisson time series auto
regression models. RESULTS: After adjusting for confounding factors (such as
seasonal variation, calendar year, temperature, humidity, and unemployment rate),
there was a significant increase in suicide (RR=1.40, 95%, CI=1.30-1.51, no. of
excess mortalities=331; 95% CI=267-391) during the 4 weeks after Lee's suicide.
This increase was more prominent in subgroups with similar characteristics to the
celebrity. In particular, the relative risk of suicide during this period was the
largest (5.24; 95% CI=3.31-8.29) in young women who used the same suicide method
as the celebrity. Moreover, the incidence of these copycat suicides during the
same time significantly increased in both genders and in all age subgroups among
those who committed suicide using the same method as the celebrity (hanging).
LIMITATIONS: It is difficult to prove conclusively that the real motivation of
the suicides was Lee's death. CONCLUSIONS: The findings from this study imply
that, if the media indiscreetly reports the suicide of a celebrity in a suicide
prone society, the copycat effect can be far-reaching and very strong,
particularly for vulnerable people.
PMID- 24355650
TI - Post-natal oogenesis: a concept for controversy that intensified during the last
decade.
AB - For decades, scientists have considered that female mammals are born with a
lifetime reserve of oocytes in the ovary, irrevocably fated to decline after
birth. However, controversy in the matter of the possible presence of oocytes and
granulosa cells that originate from stem cells in the adult mammalian ovaries has
been expanded. The restricted supply of oocytes in adult female mammals has been
disputed in recent years by supporters of neo-oogenesis, who claim that germline
stem cells (GSCs) exist in the ovarian surface epithelium (OSE) or the bone
marrow (BM). Differentiation of ovarian stem cells (OSCs) into oocytes,
fibroblast-like cells, granulosa phenotype, neural and mesenchymal type cells and
generation of germ cells from OSCs under the contribution of an OSC niche that
consists of immune system-related cells and hormonal signalling has been claimed.
Although these arguments have met with intense suspicion, their confirmation
would necessitate the revision of the current classic knowledge of female
reproductive biology.
PMID- 24355651
TI - [Variables determining the amount of care for very preterm neonates: the concept
of medical stance].
AB - OBJECTIVE: To compare the amount of medical interventions on very preterm
neonates (24-31 weeks of gestation) in two French university tertiary care
centers, one of which is involved in a Neonatal Developmental Care program. A
secondary objective is to assess whether this difference in medical interventions
can be linked to a difference in mortality and morbidity rates. METHODS: We
prospectively included all very preterm neonates free from lethal malformation
born live in these two centers between 2006 and 2010. These inclusion criteria
were met by 1286 patients, for whom we compared the rate of five selected medical
interventions: birth by caesarean section, chest intubation in the delivery room,
surfactant therapy, pharmacological treatment of patent ductus arteriosus, and
red blood cell transfusion. RESULTS: The rates of the five medical interventions
were systematically lower in the center that is involved in Neonatal
Developmental Care. There was no significant difference in survival at discharge
with no severe cerebral ultrasound scan abnormalities between the two centers.
There were, however, significantly higher rates of bronchopulmonary dysplasia and
nosocomial sepsis and longer hospital stays when the patients were not involved
in a Neonatal Developmental Care program. DISCUSSION: This benchmarking study
shows that in France, in the first decade of the 21st century, there are as many
ways to handle very preterm neonates as there are centers in which they are born.
This brings to light the concept of medical stance, which is the general care
approach prior to the treatment itself. This medical stance creates the overall
framework for the staff's decision-making regarding neonate care. The different
parameters structuring medical stance are discussed. Moreover, this study raises
the problematic issue of the aftermath of benchmarking studies when the
conclusion is an increase of morbidity in cases where procedure leads to more
interventions.
PMID- 24355652
TI - Thrombosis of the renal artery in a young woman of 23 years.
PMID- 24355653
TI - Sustained attention, selective attention and cognitive control in deaf and
hearing children.
AB - Deaf children have been characterized as being impulsive, distractible, and
unable to sustain attention. However, past research has tested deaf children born
to hearing parents who are likely to have experienced language delays. The
purpose of this study was to determine whether an absence of auditory input
modulates attentional problems in deaf children with no delayed exposure to
language. Two versions of a continuous performance test were administered to 37
deaf children born to Deaf parents and 60 hearing children, all aged 6-13 years.
A vigilance task was used to measure sustained attention over the course of
several minutes, and a distractibility test provided a measure of the ability to
ignore task irrelevant information - selective attention. Both tasks provided
assessments of cognitive control through analysis of commission errors. The deaf
and hearing children did not differ on measures of sustained attention. However,
younger deaf children were more distracted by task-irrelevant information in
their peripheral visual field, and deaf children produced a higher number of
commission errors in the selective attention task. It is argued that this is not
likely to be an effect of audition on cognitive processing, but may rather
reflect difficulty in endogenous control of reallocated visual attention
resources stemming from early profound deafness.
PMID- 24355655
TI - Diagnostic value of whole-body diffusion-weighted magnetic resonance imaging for
detection of primary and metastatic malignancies: a meta-analysis.
AB - PURPOSE: To perform a meta-analysis to evaluate the diagnostic performance of
whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) technique in
detection of primary and metastatic malignancies compared with that of whole-body
positron emission tomography/computed tomography (WB-PET/CT). MATERIALS AND
METHODS: Search Pubmed, MEDLINE, EMBASE and Cochrane Library database from
January 1984 to July 2013 for studies comparing WB-DWI with WB-PET/CT for
detection of primary and metastatic malignancies. Methodological quality was
assessed by the quality assessment of diagnostic studies (QUADAS) instrument.
Sensitivities, specificities, predictive values, diagnostic odds ratio (DOR) and
areas under the summary receiver operator characteristic curve (AUC) were
calculated. Potential threshold effect, heterogeneity and publication bias were
investigated. RESULT: Thirteen eligible studies were included, with a total of
1067 patients. There was no significant threshold effect. WB-DWI had a similar
AUC (0.966 (95% CI, 0.940-0.992) versus 0.984 (95% CI, 0.965-0.999)) with WB
PET/CT. No significant difference was detected between AUC of WB-DWI and WB
PET/CT. WB-DWI had a pooled sensitivity of 0.897 (95% CI, 0.876-0.916) and a
pooled specificity of 0.954 (95% CI, 0.944-0.962). WB-PET/CT had a pooled
sensitivity of 0.895 (95% CI, 0.865-0.920) and a pooled specificity of 0.975 (95%
CI, 0.966-0.981). Heterogeneity was found to stem primarily from data type (per
lesion versus per patient), MR sequence (DWIBS only and DWIBS with other
sequence), and primary lesion type (single type and multiple type). The Deeks's
funnel plots suggested the absence of publication bias. CONCLUSION: WB-DWI has
similar, good diagnostic performance for the detection of primary and metastatic
malignancies compared with WB-PET/CT. DWIBS with other MR sequences could further
improve the diagnostic performance. More high-quality studies regarding
comparison of WB-DWI and WB-PET/CT and combination of them in detecting
malignancies are still needed to be conducted.
PMID- 24355656
TI - Screening and detection of blunt vertebral artery injury in patients with upper
cervical fractures: the role of cervical CT and CT angiography.
AB - OBJECTIVE: To evaluate the clinical utility of nonenhanced CT (NECT)-based
screening criteria and CTA in detection of blunt vertebral artery injury (BVAI)
in trauma patients with C1 and/or C2 fractures. METHODS: We retrospectively
reviewed the clinical records of all blunt trauma patients with C1 and/or C2
fractures between 8/2006 and 9/2011. Cervical CTA was prompted by cervical
fractures involving/adjacent to a transverse foramen, and/or subluxation on NECT.
Two neuroradiologists independently reviewed the CTA studies, and graded the
BVAI. RESULTS: 210 patients were included; of these, 124 underwent CTA (21/124
with digital subtraction angiography, DSA), and 2 underwent DSA only. Overall,
30/126 suffered BVAI. Among 21 patients who underwent both CTA and DSA, there was
1 false negative and 1 false positive (both grade 1). There was strong
interobserver agreement regarding CTA-based BVAI detection (kappa=0.93, p<0.001)
and grading (kappa=0.90, p<0001). Only 3/30 BVAI patients suffered a posterior
circulation stroke; none of the patients who had a negative CTA or were not
selected for CTA, based on NECT screening criteria, suffered symptomatic stroke.
While C1/C2 comminuted fracture was more common in patients with high grade BVAI
(p=0.039), simultaneous C3-C7 comminuted fracture increased the overall BVAI risk
(p=0.011). CONCLUSION: CTA reliably detects symptomatic BVAI in patients with
upper cervical fractures. Utilization of NECT-based screening criteria such as
transverse foraminal involvement or subluxation may be adequate in deciding
whether to perform CTA, as no patients who were not selected for CTA suffered a
symptomatic stroke. However, CTA may miss lower grade, asymptomatic BVAI.
PMID- 24355657
TI - Diagnostic performance of using effervescent powder for detection and grading of
esophageal varices by multi-detector computed tomography.
AB - PURPOSE: To investigate the effect of using effervescent powder (EP) on the
efficacy of multi-detector computed tomography (MDCT) in detection and grading of
esophageal varices in cirrhotic patients by considering endoscopy as the gold
standard. MATERIALS AND METHODS: Ninety-two cirrhotic patients undergoing
biphasic liver MDCT followed by upper gastrointestinal endoscopy within 4 weeks
of MDCT were prospectively evaluated. The patients were divided into two groups
before MDCT. The first group (n=50) received effervescent powder (EP) before and
during MDCT procedure and the second group did not receive (n=42). The presence,
size and grade of the esophageal varices were evaluated. MDCT findings were
compared with endoscopic results. The sensitivity, specificity, positive
predictive value (PPV), negative predictive value (NPV) and accuracy of MDCT with
EP and without EP were calculated and compared. Correlations between the grades
of the varices for each group based on MDCT imaging and endoscopic grading were
also evaluated. RESULTS: The sensitivity, specificity, accuracy, PPV, and NPV of
MDCT were 100%, 88%, 96%, 94%, and 100%, respectively, in the EP group, whereas
they were 76%, 67%, 74%, 89%, and 43%, respectively, in the non-EP group.
Correlations between the grades of the esophageal varices on MDCT and endoscopy
were significant in both groups (r=0.94, p<0.001 for EP group and r=0.70, p<0.001
for non-EP group). CONCLUSION: During periodic CT scanning of cirrhotic patients,
use of EP increases the success rate of MDCT for detection and grading of
esophageal varices.
PMID- 24355654
TI - Autoimmune N-methyl-D-aspartate receptor encephalitis is a differential diagnosis
of infectious encephalitis.
AB - BACKGROUND: For 60% of acute febrile encephalitis cases, the cause is unknown.
Autoantibodies directed against different synaptic proteins or receptors in
patients with autoimmune encephalitis have recently been described and could
indicate a differential diagnosis of infectious encephalitis. OBJECTIVE: The aim
of this study was to retrospectively investigate the presence of autoantibodies
directed against synaptic proteins or receptors in patients with acute febrile
encephalitis. Samples were collected in France in 2007 during a national
prospective study. METHODS: A total of 253 patients with acute febrile
encephalitis were enrolled in 2007. Clinical data were collected with a
standardized questionnaire. When possible, cerebrospinal fluid CSF was collected
and stored at -80 degrees C. A total of 108 CSF samples were available for
retrospective autoantibody screening. Among the 108 patients, infectious etiology
had been detected in 38 cases (35%); of these 38 patients, 29 (27%) had viral
encephalitis, and 9 (8%) had bacterial encephalitis. No specific diagnosis was
indicated for the other 70 patients (65%). Autoantibodies were detected using a
cell-based assay in which HEK293 cells were transfected with plasmids coding for
different synaptic proteins or receptors. RESULTS: Two patients had anti-NMDA
receptor antibodies (NMDAR-Abs), and all patients were negative for anti-Lgi1,
CASPR2, GABABR, AMPAR, and mGluR5 antibodies. The two patients with NMDAR-Abs
presented neurological and psychiatric symptoms typical of NMDAR-Abs
encephalitis. CONCLUSIONS: Autoimmune etiology seems to be rare (less than 2%) in
patients with acute febrile encephalitis. However, patients should be
systematically screened for the presence of NMDAR-Abs, particularly patients
presenting with psychiatric symptoms.
PMID- 24355658
TI - Oxygen-enhanced MRI for patients with connective tissue diseases: comparison with
thin-section CT of capability for pulmonary functional and disease severity
assessment.
AB - PURPOSE: To prospectively and directly compare oxygen-enhanced (O2-enhanced) MRI
with thin-section CT for pulmonary functional loss and disease severity
assessment in connective tissue disease (CTD) patients with interstitial lung
disease (ILD). MATERIALS AND METHODS: Thin-section CT, O2-enhanced MRI, pulmonary
function test and serum KL-6 were administered to 36 CTD patients with ILD (23
men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men,
and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map
was generated from O2-enhanced MRI and mean relative enhancement ratio (MRER) for
each subject was calculated from all ROI measurements. CT-assessed disease
severity was evaluated with a visual scoring system from each of the thin-section
CT data. MRER and CT-assessed disease severities of CTD patients with and without
ILD were then statistically compared. To assess capability for pulmonary
functional loss and disease severity assessment in CTD patients, correlations of
MRER and CT-assessed disease severity with pulmonary functional parameters and
serum KL-6 in all subjects were statistically determined. RESULTS: MRER and CT
assessed disease severity showed significant differences between CTD patients
with (MRER: 0.15 +/- 0.08, CT-assessed disease severity: 13.0 +/- 7.4%) and
without ILD (MRER: 0.25 +/- 0.06, p=0.0011; CT-assessed disease severity: 1.6 +/-
1.6%, p<0.0001). MRER and CT-assessed disease severity correlated significantly
with pulmonary functional parameters and serum KL-6 in all subjects (0.61 <= r <=
0.79, p<0.05). CONCLUSION: O2-enhanced MRI was found to be as useful as thin
section CT for pulmonary functional loss and disease severity assessment of CTD
patients with ILD.
PMID- 24355659
TI - Whole-body CT for lymphoma staging: feasibility of halving radiation dose and
risk by iterative image reconstruction.
AB - OBJECTIVES: Patients with lymphoma are at higher-risk of secondary malignancies
mainly due to effects of cancer therapy as well as frequent radiological
surveillance. We thus aimed to investigate the objective and subjective image
quality as well as radiation exposure and risk of full-dose standard (FDS), full
dose iterative (FDI), and half-dose iterative (HDI) image reconstruction in
patients with lymphoma. MATERIAL AND METHODS: In 100 lymphoma patients, contrast
enhanced whole-body staging was performed on a dual-source CT. To acquire full
dose and half-dose CT data simultaneously, the total current-time product was
equally distributed on both tubes operating at 120 kV. HDI reconstructions were
calculated by using only data from one tube. Quantitative image quality was
assessed by measuring image noise in different tissues of the neck, thorax, and
abdomen. Overall diagnostic image quality was assessed using a 5-point Likert
scale. Radiation doses and risks were estimated for a male and female reference
person. RESULTS: For all anatomical regions apart from the lungs image noise was
significantly lower and the overall subjective image quality significantly better
when using FDI and HDI instead of FDS reconstruction (p<0.05). For the half-dose
protocol, the risk to develop a radiation-induced cancer was estimated to be less
than 0.11/0.19% for an adult male/female. CONCLUSIONS: Image quality of FDI and
more importantly of HDI is superior to FDS reconstruction, thus enabling to halve
radiation dose and risk to lymphoma patients.
PMID- 24355660
TI - Sonographic and clinical features of collateral vessels at the splenic hilum in
cirrhosis.
AB - AIM: To examine the sonographic features of shunt vessels derived from the
splenic vein at splenic hilum (SS), and explore the relationship between the SS
pattern and clinical presentations. MATERIALS AND METHODS: This prospective study
in cirrhotic patients consisted of study I (n = 15), which compared the
anatomical features of SS at ultrasonography versus angiography, and study II (n
= 233), which examined the incidence/haemodynamics of SS and SS-related
presentations. RESULTS: Study I showed that SS1 (running toward the upper pole of
the spleen) corresponded to short gastric veins, and SS2 (running toward the
lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In
study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111),
SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence
of gastric cardia varices was significantly higher in patients with SS2 (6/19)
than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric
fundal varices was significantly higher in patients with SS1 (44/86) than in
those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no
difference in the incidence of oesophageal varices among the three SS groups. The
Child-Pugh score and grade of ascites was significantly worse in patients with
SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade
was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001)
compared to SS1. CONCLUSION: The SS pattern facilitates estimation of the
possible manifestations, indicating the direction of clinical management of
cirrhosis patients. Potential poor liver function is noted in patients with SS3.
PMID- 24355661
TI - Association between visceral, cardiac and sensorimotor polyneuropathies in
diabetes mellitus.
AB - AIMS: Gastrointestinal complaints are common in diabetes mellitus. However, its
association to peripheral sensorimotor and autonomic neuropathies is not well
investigated. The aim was to assess skin, muscle, bone and visceral sensitivity
in diabetes patients with sensorimotor neuropathy, and correlate these with
gastrointestinal symptoms and degree of cardiac autonomic neuropathy. METHODS:
Twenty patients with sensorimotor neuropathy (65% type 2 diabetes, aged 58.3+/
12.0 years, diabetes duration 15.8+/-10.0 years) and 16 healthy controls were
recruited. Cutaneous sensitivity to von Frey filaments, mechanical allodynia,
muscle/bone/rectosigmoid sensitivities, and heart rate variability were examined.
Gastrointestinal symptom scores (PAGI-SYM) and health-related quality of life (SF
36) were also recorded. RESULTS: Patients displayed hypesthesia to von Frey
filaments (p=0.028), but no difference to muscle and bone pain sensitivities.
Also, patients were hyposensitive to multimodal rectal stimulations (all p<0.05),
although they suffered more gastrointestinal complaints. Heart rate variability
was reduced in the patient cohort. Rectal mechanical and cutaneous sensitivities
correlated (p<0.001), and both were associated with heart rate variability as
well as PAGI-SYM and SF-36 scores (p<0.01). CONCLUSIONS: In diabetic sensorimotor
neuropathy there is substantial evidence of concomitant cutaneous, cardiac and
visceral autonomic neuropathies. The neuropathy may reduce quality of life and
explain the higher prevalence of gastrointestinal complaints.
PMID- 24355662
TI - Parental brevity linked to cardiometabolic risk in diabetic descendants.
AB - BACKGROUND: Non-diabetic offspring from long-lived parents benefit from lowered
CV risk. No study investigated the effects of parental lifespan on their progeny
when offspring have T2DM. This study assessed CV and metabolic features of T2DM
offspring according to parental lifespan. PATIENTS & METHODS: 558 T2DM patients
were questioned on parental longevity (paternal and/or maternal lifespan >= 80
years); mean age 66 (11) years; male:female 66:34; divided into 6 groups: long
lived father [LLF] (n = 143); short-lived father [SLF] (n = 262); long-lived
mother [LLM] (n = 229); short-lived mother [SLM] (n = 176); long-lived father and
long-lived mother [LLF & LLM] (n = 82); and short-lived father and/or short-lived
mother [SLF &/or SLM] (n = 323). RESULTS: Age was similar in [LLF & LLM] and [SLF
&/or SLM]. Diabetes duration was longer in [SLF &/or SLM] (p 0.0073). Body
composition, hypertension, hepatic steatosis and metabolic syndrome (MetS) were
similar in both groups, [SLF &/or SLM] having a higher MetS score: 3.79 (1.12)
vs. 3.48 (1.12) (p 0.0257). Fasting insulinemia was higher in [SLF &/or SLM] (p
0.0001), who were more insulin resistant (+10%: p 0.0440). HbA1c was higher
(+0.36%) in [SLF &/or SLM] (p 0.0138). LDL-C; non-HDL-C; and apoB100 were similar
in both groups, whereas HDL-C and apoA-I were higher in [LLF & LLM] (p 0.0233 and
p 0.0179). Prevalence and severity of atherogenic dyslipidemia were raised in
[SLF &/or SLM], by 53% (prevalence) and 13% (log[TG]/HDL-C) (p 0.0172 and p
0.0067). CONCLUSION: Bilateral reductions in parental longevity are linked to
unfavorable cardiometabolic phenotype in T2DM descendants, with worsened insulin
resistance and atherogenic dyslipidemia among 1st-degree offspring.
PMID- 24355663
TI - Diabetes status differentiates endothelial function and plasma nitrite response
to exercise stress in peripheral arterial disease following supervised training.
AB - AIMS: To determine if type 2 diabetes mellitus (T2D) differentiates endothelial
function and plasma nitrite response (a marker of nitric oxide bioavailability)
during exercise in peripheral arterial disease (PAD) subjects prior to and
following 3 months supervised exercise training (SET). METHODS: In subjects with
T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using
brachial artery flow-mediated dilation. On a separate day, venous blood draws
were performed at rest and 10 min following a symptom-limited graded treadmill
test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by
reductive chemiluminescence. All testing was repeated following 3 months of SET.
RESULTS: Prior to training both groups demonstrated endothelial dysfunction,
which was correlated with a net decrease in plasma nitrite following a SL-GXT (p
<= 0.05). Following SET, the PAD-only group demonstrated an improvement in
endothelial function (p <= 0.05) and COT (p <= 0.05), which was related to a net
increase in plasma nitrite following the SL-GXT (both p <= 0.05). The T2D+PAD
group had none of these increases. CONCLUSIONS: T2D in the presence of PAD
attenuated improvements in endothelial function, net plasma nitrite, and COT
following SET. This suggests that T2D maybe associated with an inability to
endogenously increase vascular NO bioavailability to SET.
PMID- 24355664
TI - MiR-568 inhibits the activation and function of CD4+ T cells and Treg cells by
targeting NFAT5.
AB - CD4(+) T cells play critical roles in orchestrating adaptive immune responses.
Their activation and proliferation are critical steps that occur before they
execute their biological functions. Despite the important role of this process,
the underlying molecular events are not fully understood. MicroRNAs (miRNAs) have
been shown to play important roles in lymphocyte development and function.
However, the miRNAs that regulate T-cell differentiation, activation and
proliferation are still largely unknown. In our previous study, using a miRNA
array, we found that several miRNAs (including miR-202, 33b, 181c, 568 and 576)
are differentially expressed between resting and activated CD4(+) T cells. In
this study, we focused on the function of miR-568 during CD4(+) T-cell
activation. We showed that the expression level of miR-568 decreased during the
activation of T cells, including Jurkat cells and human peripheral blood CD4(+) T
cells. When Jurkat or human peripheral blood CD4(+) T cells were transfected with
miR-568 mimics, cell activation was significantly inhibited, as shown by the
inhibited expression of activation markers such as CD25, CD69 and CD154;
decreased IL-2 production; and inhibited cell proliferation. Using software
predictions and confirmatory experiments, we demonstrated that nuclear factor of
activated T cells 5 (NFAT5) is a target of miR-568. Treg cells are an important
CD4(+) T-cell subpopulation, so we also evaluated the function of miR-568 in Treg
cell activation and differentiation. We showed that the miR-568 level decreased,
while the NFAT5 protein level increased during CD4(+)CD25(+) Treg-cell
activation, and the transfection of miR-568 mimics inhibited the NFAT5
expression, inhibited the production of both TGF-beta and IL-10 and also
inhibited the proliferation of Treg cells. Our further study showed that over
expression of miR-568 can inhibit Treg-cell differentiation and can inhibit the
suppressive effect of these cells on effector cells. In addition, inhibition of
NFAT5 by siRNA-mediated knockdown can inhibit the activation and differentiation
of Treg cells. These findings reveal that miR-568 can inhibit the activation and
function of both CD4(+) T cells and Treg cells by targeting NFAT5. Since miR-568
plays an important role in both CD4(+) T cells and Treg cells, these findings may
provide leads for the development of novel treatments for human inflammatory and
autoimmune diseases.
PMID- 24355665
TI - Seasonal influenza vaccination at school: a randomized controlled trial.
AB - BACKGROUND: Influenza vaccination coverage for U.S. school-aged children is below
the 80% national goal. Primary care practices may not have the capacity to
vaccinate all children during influenza vaccination season. No real-world models
of school-located seasonal influenza (SLV-I) programs have been tested. PURPOSE:
Determine the feasibility, sustainability, and impact of an SLV-I program
providing influenza vaccination to elementary school children during the school
day. DESIGN: In this pragmatic randomized controlled trial of SLV-I during two
vaccination seasons, schools were randomly assigned to SLV-I versus standard of
care. Seasonal influenza vaccine receipt, as recorded in the state immunization
information system (IIS), was measured. SETTING/PARTICIPANTS: Intervention and
control schools were located in a single western New York county. Participation
(intervention or control) included the sole urban school district and suburban
districts (five in Year 1, four in Year 2). INTERVENTION: After gathering
parental consent and insurance information, live attenuated and inactivated
seasonal influenza vaccines were offered in elementary schools during the school
day. MAIN OUTCOME MEASURES: Data on receipt of >=1 seasonal influenza vaccination
in Year 1 (2009-2010) and Year 2 (2010-2011) were collected on all student grades
K through 5 at intervention and control schools from the IIS in the Spring of
2010 and 2011, respectively. Additionally, coverage achieved through SLV-I was
compared to coverage of children vaccinated elsewhere. Preliminary data analysis
for Year 1 occurred in Spring 2010; final quantitative analysis for both years
was completed in late Fall 2012. RESULTS: Results are shown for 2009-2010 and
2010-2011, respectively: Children enrolled in suburban SLV-I versus control
schools had vaccination coverage of 47% vs 36%, and 52% vs 36% (p<0.0001 both
years). In urban areas, coverage was 36% vs 26%, and 31% vs 25% (p<0.001 both
years). On multilevel logistic analysis with three nested levels (student,
school, school district) during both vaccination seasons, children were more
likely to be vaccinated in SLV-I versus control schools; ORs were 1.6 (95%
CI=1.4, 1.9; p<0.001) and 1.5 (95% CI=1.3, 1.8; p<0.001). CONCLUSIONS: Delivering
influenza vaccine during school is a promising approach to improving pediatric
influenza vaccination coverage. TRIAL REGISTRY: ClinicalTrials.govNCT01224301.
PMID- 24355667
TI - Weight-loss maintenance for 10 years in the National Weight Control Registry.
AB - BACKGROUND: The challenge of weight-loss maintenance is well known, but few
studies have followed successful weight losers over an extended period or
evaluated the effect of behavior change on weight trajectories. PURPOSE: To study
the weight-loss trajectories of successful weight losers in the National Weight
Control Registry (NWCR) over a 10-year period, and to evaluate the effect of
behavior change on weight-loss trajectories. METHODS: A 10-year observational
study of self-reported weight loss and behavior change in 2886 participants (78%
female; mean age 48 years) in the NWCR who at entry had lost at least 30 lbs
(13.6 kg) and kept it off for at least one year. Data were collected in 1993
2010; analysis was conducted in 2012. MAIN OUTCOME MEASURES: Weight loss
(kilograms; percent weight loss from maximum weight). RESULTS: Mean weight loss
was 31.3 kg (95% CI=30.8, 31.9) at baseline, 23.8 kg (95% CI=23.2, 24.4) at 5
years and 23.1+/-0.4 kg (95% CI=22.3, 23.9) at 10 years. More than 87% of
participants were estimated to be still maintaining at least a 10% weight loss at
Years 5 and 10. Larger initial weight losses and longer duration of maintenance
were associated with better long-term outcomes. Decreases in leisure-time
physical activity, dietary restraint, and frequency of self-weighing and
increases in percentage of energy intake from fat and disinhibition were
associated with greater weight regain. CONCLUSIONS: The majority of weight lost
by NWCR members is maintained over 10 years. Long-term weight-loss maintenance is
possible and requires sustained behavior change.
PMID- 24355666
TI - A new scale of the U.S. alcohol policy environment and its relationship to binge
drinking.
AB - BACKGROUND: Of outcomes related to excessive drinking, binge drinking accounts
for approximately half of alcohol-attributable deaths, two thirds of years of
potential life lost, and three fourths of economic costs. The extent to which the
alcohol policy environment accounts for differences in binge drinking in U.S.
states is unknown. PURPOSE: The goal of the study was to describe the development
of an Alcohol Policy Scale (APS) designed to measure the aggregate state-level
alcohol policy environment in the U.S. and assess the relationship of APS scores
to state-level adult binge drinking prevalence in U.S. states. METHODS: Policy
efficacy and implementation ratings were developed with assistance from a panel
of policy experts. Data on 29 policies in 50 states and Washington DC from 2000
2010 were collected from multiple sources and analyzed between January 2012 and
January 2013. Five methods of aggregating policy data to calculate APS scores
were explored; all but one was weighted for relative policy efficacy and/or
implementation. Adult (aged >=18 years) binge drinking prevalence data from 2001
2010 was obtained from the Behavioral Risk Factor Surveillance System surveys.
APS scores from a particular state-year were used to predict binge drinking
prevalence during the following year. RESULTS: All methods of calculating APS
scores were significantly correlated (r >0.50), and all APS scores were
significantly inversely associated with adult binge drinking prevalence.
Introducing efficacy and implementation ratings optimized goodness of fit in
statistical models (e.g., unadjusted beta=-3.90, p<0.0001, R(2)=0.31).
CONCLUSIONS: The composite measure(s) of the alcohol policy environment have
internal and construct validity. Higher APS scores (representing stronger policy
environments) were associated with less adult binge drinking and accounted for a
substantial proportion of the state-level variation in binge drinking among U.S.
states.
PMID- 24355668
TI - Daily self-weighing and adverse psychological outcomes: a randomized controlled
trial.
AB - BACKGROUND: Despite evidence that daily self-weighing is an effective strategy
for weight control, concerns remain regarding the potential for negative
psychological consequences. PURPOSE: The goal of the study was to examine the
impact of a daily self-weighing weight-loss intervention on relevant
psychological constructs. DESIGN: A 6-month RCT. SETTING/PARTICIPANTS: The study
sample (N=91) included overweight men and women in the Chapel Hill NC area.
INTERVENTION: Between February and August 2011, participants were randomly
assigned to a daily self-weighing intervention or delayed-intervention control
group. The 6-month intervention included daily self-weighing for self-regulation
of diet and exercise behaviors using an e-scale that transmitted weights to a
study website. Weekly e-mailed lessons and tailored feedback on daily self
weighing adherence and weight-loss progress were provided. MAIN OUTCOME MEASURES:
Self-weighing frequency was measured throughout the study using e-scales. Weight
was measured in-clinic at baseline, 3 months, and 6 months. Psychological
outcomes were assessed via self-report at the same time points. RESULTS: In 2012,
using linear mixed models and generalized estimating equation models, there were
no significant differences between groups in depressive symptoms, anorectic
cognitions, disinhibition, susceptibility to hunger, and binge eating. At 6
months, there was a significant group X time interaction for body dissatisfaction
(p=0.007) and dietary restraint (p<0.001), with the intervention group reporting
lower body dissatisfaction and greater dietary restraint compared to controls.
CONCLUSIONS: Results indicate that a weight-loss intervention that focuses on
daily self-weighing does not cause adverse psychological outcomes. This suggests
that daily self-weighing is an effective and safe weight-control strategy among
overweight adults attempting to lose weight. TRIAL REGISTRATION: This study is
registered at clinicaltrials.gov NCT01369004.
PMID- 24355669
TI - Workplace sitting and height-adjustable workstations: a randomized controlled
trial.
AB - BACKGROUND: Desk-based office employees sit for most of their working day. To
address excessive sitting as a newly identified health risk, best practice
frameworks suggest a multi-component approach. However, these approaches are
resource intensive and knowledge about their impact is limited. PURPOSE: To
compare the efficacy of a multi-component intervention to reduce workplace
sitting time, to a height-adjustable workstations-only intervention, and to a
comparison group (usual practice). DESIGN: Three-arm quasi-randomized controlled
trial in three separate administrative units of the University of Queensland,
Brisbane, Australia. Data were collected between January and June 2012 and
analyzed the same year. SETTING/PARTICIPANTS: Desk-based office workers aged 20
65 (multi-component intervention, n=16; workstations-only, n=14; comparison,
n=14). INTERVENTION: The multi-component intervention comprised installation of
height-adjustable workstations and organizational-level (management consultation,
staff education, manager e-mails to staff) and individual-level (face-to-face
coaching, telephone support) elements. MAIN OUTCOME MEASURES: Workplace sitting
time (minutes/8-hour workday) assessed objectively via activPAL3 devices worn for
7 days at baseline and 3 months (end-of-intervention). RESULTS: At baseline, the
mean proportion of workplace sitting time was approximately 77% across all groups
(multi-component group 366 minutes/8 hours [SD=49]; workstations-only group 373
minutes/8 hours [SD=36], comparison 365 minutes/8 hours [SD=54]). Following
intervention and relative to the comparison group, workplace sitting time in the
multi-component group was reduced by 89 minutes/8-hour workday (95% CI=-130, -47
minutes; p<0.001) and 33 minutes in the workstations-only group (95% CI=-74, 7
minutes, p=0.285). CONCLUSIONS: A multi-component intervention was successful in
reducing workplace sitting. These findings may have important practical and
financial implications for workplaces targeting sitting time reductions. CLINICAL
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 00363297.
PMID- 24355670
TI - Effectiveness of a multimodal online well-being intervention: a randomized
controlled trial.
AB - BACKGROUND: Well-being encompasses physical, psychological, and social aspects of
health and predicts healthcare utilization and expenditures. Despite their
potential clinical impact, interventions that leverage social network effects to
target well-being are uncommon. PURPOSE: Using a pragmatic design, to evaluate
the effectiveness of an online well-being intervention as part of ongoing program
development. DESIGN: Randomized, placebo-controlled, parallel-group trial with
longitudinal outcome measurements at baseline, 30 days, and 90 days.
PARTICIPANTS/SETTING: A total of 1503 U.S.-based adults were enrolled.
Recruitment, eligibility verification, and baseline data collection were
conducted entirely online; follow-up took place online or by phone. The study was
conducted in 2012. INTERVENTION: A multimodal e-mail-, web-, and mobile-based
intervention (Daily Challenge), in which participants receive daily suggestions
of small health actions that they complete in a social environment. A traditional
weekly health newsletter served as control. MAIN OUTCOME MEASURE: Overall well
being as measured by the Individual-level Well-Being Assessment and Scoring
Method (scale: 0 to 100). RESULTS: Follow-up rates reached 68.7% (n=1032) at 30
days and 62.6% (n=940) at 90 days. Overall, 84.6% of treatment group participants
visited the website, and 76.5% opened program e-mails (vs 51.1% in the control
group). Daily Challenge improved well-being significantly more than control at 30
days (2.27 points, p=0.004) and at 90 days (2.35 points, p=0.004). A dose
response for intensity of use was observed at 30 days (p=0.001) and 90 days
(p=0.003). Well-being improvement was greater in participants with than without
social ties in the program (at 30 days: p=0.02; at 90 days: p=0.003).
CONCLUSIONS: A multimodal online intervention leveraging social network effects
significantly improved well-being over control. Higher levels of participation as
well as increasing levels of social integration were associated with greater
improvement in well-being. TRIAL REGISTRATION: www.clinicaltrials.gov
(NCT01586949).
PMID- 24355672
TI - Overestimated crash risks of young and elderly drivers.
AB - BACKGROUND: Young and elderly drivers are reported to have markedly greater crash
rates than drivers of other ages, but they travel less frequently and represent a
minority of road users. Consequently, many crashes involving young or elderly
drivers also involve drivers of middle age ranges who travel more frequently.
PURPOSE: To examine crash rates of young and elderly drivers, controlling for
ages of all drivers involved in collisions. METHODS: A retrospective longitudinal
study conducted on population-wide two-vehicle crashes reported in Great Britain
from 2002 through 2010 for driver age ranges (17-20, 21-29, 30-39, 40-49, 50-59,
60-69, >=70 years) and individual driver ages among those aged 17-20 years.
Annual trips made, recorded as part of a National Travel Survey, were used to
estimate trip-based driver crash rates. RESULTS: Crash rates of drivers aged 17
20 years were not significantly different from crash rates of drivers aged 21-29
years (rate ratio=1.14; 95% CI=0.96, 1.33) when controlling for ages of both
drivers involved in two-car collisions, and drivers aged 17 years had the lowest
crash rate among drivers aged 17-20 years. Crash rates of drivers aged >=70 years
equaled crash rates of drivers aged 60-69 years (rate ratio=1.00; 95% CI=0.77,
1.32) and were 1.40 times (95% CI=1.10, 1.78) lower than crash rates of drivers
aged 50-59 years. CONCLUSIONS: The current findings are in contrast with reports
of high crash risks among young and elderly drivers, and suggest that previous
reports may have overestimated the crash risks of these drivers by failing to
control for ages of all drivers involved in collisions.
PMID- 24355671
TI - Understanding administrative evidence-based practices: findings from a survey of
local health department leaders.
AB - BACKGROUND: There are sparse data showing the extent to which evidence-based
public health is occurring among local health departments. PURPOSE: The purpose
of the study was to describe the patterns and predictors of administrative
evidence-based practices (structures and activities that are associated with
performance measures) in a representative sample of local health departments in
the U.S. METHODS: A cross-sectional study of 517 local health department
directors was conducted from October through December 2012 (analysis in January
March 2013). The questions on administrative evidence-based practices included 19
items based on a recent literature review (five broad domains: workforce
development, leadership, organizational climate and culture, relationships and
partnerships, financial processes). RESULTS: There was a wide range in
performance among the 19 individual administrative evidence-based practices,
ranging from 35% for providing access to current information on evidence-based
practices to 96% for funding via a variety of sources Among the five domains,
values were generally lowest for organizational climate and culture (mean for the
domain=49.9%) and highest for relationships and partnerships (mean for the
domain=77.1%). Variables associated with attaining the highest tertile of
administrative evidence-based practices included having a population jurisdiction
of 25,000 or larger (adjusted ORs [aORs] ranging from 4.4 to 7.5) and state
governance structure (aOR=3.1). CONCLUSIONS: This research on the patterns and
predictors of administrative evidence-based practices in health departments
provides information on gaps and areas for improvement that can be linked with
ongoing quality improvement processes.
PMID- 24355673
TI - Completion of advance directives among U.S. consumers.
AB - BACKGROUND: Current, ongoing national surveys do not include questions about end
of-life (EOL) issues. In particular, population-based data are lacking regarding
the factors associated with advance directive completion. PURPOSE: To
characterize U.S. adults who did and did not have an advance directive and
examine factors associated with their completion, such as the presence of a
chronic condition and regular source of health care. METHODS: Data were analyzed
in 2013 from adults aged 18 years and older who participated in the 2009 or 2010
HealthStyles Survey, a mail panel survey designed to be representative of the
U.S. population. Likelihood ratio tests were used to examine the associations
between advance directive completion and demographic and socioeconomic variables
(education, income, employment status); presence of a chronic condition; regular
source of health care; and self-reported EOL concerns or discussions. Multiple
logistic regression analyses identified independent predictors related to advance
directive completion. RESULTS: Of the 7946 respondents, 26.3% had an advance
directive. The most frequently reported reason for not having one was lack of
awareness. Advance directive completion was associated with older age, more
education, and higher income and was less frequent among non-white respondents.
Respondents with advance directives also were more likely to report having a
chronic disease and a regular source of care. Advance directives were less
frequent among those who reported not knowing if they had an EOL concern.
CONCLUSIONS: These data indicate racial and educational disparities in advance
directive completion and highlight the need for education about their role in
facilitating EOL decisions.
PMID- 24355674
TI - Health and economic impact of breast cancer mortality in young women, 1970-2008.
AB - BACKGROUND: Breast cancer is the second-leading cause of cancer-related deaths
among women aged <50 years. Studies on the effects of breast cancer mortality
among young women are limited. PURPOSE: To assess trends in breast cancer
mortality rates among women aged 20-49 years, estimate years of potential life
lost (YPLL), and the value of productivity losses due to premature mortality.
METHODS: Age-adjusted rates and rate ratios (RRs) were calculated using 1970-2008
U.S. mortality data. Breast cancer mortality rates over time were assessed using
Joinpoint regression modeling. YPLL was calculated using number of cancer deaths
and the remaining life expectancy at the age of death. Value of productivity
losses was estimated using the number of deaths and the present value of future
lifetime earnings. RESULTS: From 1970 to 2008, the age-adjusted breast cancer
mortality rate among young women was 12.02/100,000. Rates were higher in the
Northeast (RR=1.03, 95% CI, 1.02-1.04). The annual decline in breast cancer
mortality rates among blacks was smaller (-0.68%) compared with whites (-2.02%).
The total number of deaths associated with breast cancer was 225,866, which
accounted for an estimated 7.98 million YPLL. The estimated total productivity
loss in 2008 was $5.49 billion and individual lifetime lost earnings were $1.10
million. CONCLUSIONS: Considering the effect of breast cancer on women of working
age and the disproportionate impact on black women, more age-appropriate
interventions with multiple strategies are needed to help reduce these
substantial health and economic burdens, improve survival, and in turn reduce
productivity costs associated with premature death.
PMID- 24355676
TI - Parents' knowledge, attitude, and use of child restraints, Shantou, China.
AB - BACKGROUND: China has not adopted national policies for child safety restraints
in cars, although children are increasingly traveling in cars. OBJECTIVE: To
describe child restraint use, and parents' knowledge of and attitude toward child
restraint in Shantou, China. METHODS: An observational study and driver survey on
child restraint use was conducted in the Southeast China city of Shantou in 2012.
Observational sites included 22 middle schools, 31 primary schools, 24
kindergartens, and 4 hospitals. Drivers were asked about their knowledge of and
attitude toward the use of child restraints. In September 2012, multivariate
regression was used to evaluate the factors associated with increased child
restraint use. RESULTS: Of 3333 children observed in vehicles, only 22 (0.6%)
children were secured in child safety seats or booster seats and 292 (8.7%)
children were wearing seatbelts. More than half (n=508, 56.1%) of the infants or
toddlers were riding on the laps of adults. Of 1069 drivers who responded to the
survey, more than 62% thought it was necessary to use child restraint while
traveling in a car. The drivers' higher education status (OR=1.56, 95% CI=1.07,
2.27) and seatbelt use (OR=4.00, 95% CI=2.56, 6.25) were associated with
increased child restraint use. Parents (OR=0.55, 95% CI=0.34, 0.88) and male
drivers (OR=0.61, 95% CI=0.46, 0.81) had reduced odds of children properly rear
seated. CONCLUSIONS: Child restraint use is very low in China, although the
majority of drivers had positive attitudes about child restraint. These findings
indicate that child restraint policies and educational approaches are urgently
needed in China.
PMID- 24355675
TI - Physicians' human papillomavirus vaccine recommendations, 2009 and 2011.
AB - BACKGROUND: Physician recommendation is a key predictor of human papillomavirus
(HPV) vaccine uptake. Understanding factors associated with recommendation is
important for efforts to increase current suboptimal vaccine uptake. PURPOSE:
This study aimed to examine physician recommendations to vaccinate female
patients aged 11-26 years, in 2009 and 2011, at 3 and 5 years postvaccine
licensure, respectively. A second aim was to identify trends in factors
associated with vaccine recommendation for ages 11 and 12 years. METHODS:
Nationally representative samples of physicians practicing family medicine,
pediatrics, and obstetrics and gynecology were randomly selected from the
American Medical Association Physician Masterfile (n=1538 in 2009, n=1541 in
2011). A mailed survey asked physicians about patient and clinical practice
characteristics; immunization support; and frequency of HPV vaccine
recommendation ("always" >=75% of the time vs other). Analyses were conducted in
2012. RESULTS: Completed surveys were received from 1013 eligible physicians (68%
response rate) in 2009 and 928 (63%) in 2011. The proportion of physicians who
reported always recommending HPV vaccine increased significantly from 2009 to
2011 for patients aged 11 or 12 years (35% vs 40%, respectively; p=0.03), but not
for patients aged 13-17 years (53% vs 55%; p=0.28) or 18-26 years (50% vs 52%;
p=0.52). Physician specialty, age, and perceived issues/barriers to vaccination
were associated with vaccine recommendation for patients aged 11 or 12 in both
years. CONCLUSIONS: Results suggest a modest increase in recommendations for HPV
vaccination of girls aged 11 or 12 years over a 2-year period; however,
recommendations remain suboptimal for all age groups despite national
recommendations for universal immunization.
PMID- 24355677
TI - Family emergency preparedness plans in severe tornadoes.
AB - BACKGROUND: Tornadoes, with warnings usually issued just minutes before their
touchdowns, pose great threats to properties and people's physical and mental
health. Few studies have empirically investigated the association of family
emergency preparedness planning and observed protective behaviors in the context
of tornadoes. PURPOSE: The purpose of this study was to examine predictors for
the action of taking shelter at the time of tornadoes. Specifically, this study
investigated whether having a family emergency preparedness plan was associated
with higher likelihood of taking shelter upon receiving tornado warnings. This
study also examined the effects of socioeconomic status and functional
limitations on taking such actions. METHODS: A telephone survey based on random
sampling was conducted in 2012 with residents in Tuscaloosa AL and Joplin MO.
Each city experienced considerable damages, injuries, and casualties after severe
tornadoes (EF-4 and EF-5) in 2011. The working sample included 892 respondents.
Analysis was conducted in early 2013. RESULTS: Logistic regression identified
emergency preparedness planning as the only shared factor that increased the
likelihood of taking shelter in both cities and the only significant factor in
Joplin. In Tuscaloosa, being female and white also increased the likelihood of
taking shelter. Disability was not found to have an effect. CONCLUSIONS: This
study provided empirical evidence on the importance of having a family emergency
preparedness plan in mitigating the risk of tornadoes. The findings could be
applied to other rapid-onset disasters.
PMID- 24355678
TI - Dietary assessment in food environment research: a systematic review.
AB - CONTEXT: The existing evidence on food environments and diet is inconsistent,
potentially because of heterogeneity in measures used to assess diet. The
objective of this review, conducted in 2012-2013, was to examine measures of
dietary intake utilized in food environment research. EVIDENCE ACQUISITION:
Included studies were published from January 2007 through June 2012 and assessed
relationships between at least one food environment exposure and at least one
dietary outcome. Fifty-one articles were identified using PubMed, SCOPUS, Web of
Knowledge, and PsycINFO; references listed in the papers reviewed and relevant
review articles; and the National Cancer Institute's Measures of the Food
Environment website. The frequency of the use of dietary intake measures and
assessment of specific dietary outcomes were examined, as were patterns of
results among studies using different dietary measures. EVIDENCE SYNTHESIS: The
majority of studies used brief instruments, such as screeners or one or two
questions, to assess intake. Food frequency questionnaires were used in about a
quarter of studies, one in ten used 24-hour recalls, and fewer than one in 20
used diaries. Little consideration of dietary measurement error was evident.
Associations between the food environment and diet were more consistently in the
expected direction in studies using less error-prone measures. CONCLUSIONS: There
is a tendency toward the use of brief dietary assessment instruments with low
cost and burden rather than more detailed instruments that capture intake with
less bias. Use of error-prone dietary measures may lead to spurious findings and
reduced power to detect associations.
PMID- 24355680
TI - Author response.
PMID- 24355679
TI - Childhood obesity policy research and practice: evidence for policy and
environmental strategies.
AB - Investigators developed a review system to evaluate the growing literature on
policy and environmental strategies to prevent childhood obesity. More than 2000
documents published between January 2000 and May 2009 in the scientific and grey
literature were identified (2008-2009) and systematically analyzed (2009-2012).
These focused on policy or environmental strategies to reduce obesity/overweight,
increase physical activity, and/or improve nutrition/diet among youth (aged 3-18
years). Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and
Maintenance) framework, investigators abstracted studies of 24 intervention
strategies and assessed evidence for their effectiveness (i.e., study design,
intervention duration, and outcomes) and population impact (i.e., effectiveness
and reach--participation or exposure, and representativeness) in 142 evaluation
study groupings and 254 associational study groupings (n=396 groupings of 600
peer-reviewed studies). The 24 strategies yielded 25 classifications (school
wellness policies yielded nutrition and physical activity classifications): 1st
tier effective (n=5); 2nd-tier effective (n=6); "promising" (n=5); or "emerging"
(n=9). Evidence for intervention effectiveness was reported in 56% of the
evaluation, and 77% of the associational, study groupings. Among the evaluation
study groupings, only 49% reported sufficient data for population impact ratings,
and only 22% qualified for a rating of high population impact. Effectiveness and
impact ratings were summarized in graphic evidence maps, displaying
effects/associations with behavioral and obesity/overweight outcomes. This paper
describes the results and products of the review, with recommendations for policy
research and practice.
PMID- 24355681
TI - U.S. Preventive Services Task Force diabetes screening.
PMID- 24355682
TI - Mass gathering-related mask use during 2009 pandemic influenza A (H1N1) and
Middle East respiratory syndrome coronavirus.
PMID- 24355683
TI - Vaccines and pregnancy: past, present, and future.
AB - Vaccination during pregnancy with certain vaccines can prevent morbidity and
mortality in pregnant women and their infants. However, previous recommendations
often focused on the potential risks of vaccines to the fetus when used during
pregnancy. In recent years, additional data have become available on the absence
of increased risks for adverse events associated with vaccines when administered
during pregnancy and on their benefits to mothers and infants. Currently two
vaccines - (i) inactivated influenza, and (ii) tetanus toxoid, reduced diphtheria
toxoid and acellular pertussis (Tdap) - are recommended for use by all pregnant
women by the United States Advisory Committee on Immunization Practices. Here we
review the history of vaccination during pregnancy, the current status of
recommendations for vaccination during pregnancy in the USA, and the potential
for future advances in this area, including key barriers that must be overcome to
accommodate these advances.
PMID- 24355684
TI - Mineralocorticoid receptor and heat shock protein expression levels in peripheral
lymphocytes from war trauma-exposed men with and without PTSD.
AB - Alterations in the number and functional status of mineralocorticoid (MR) and
glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic
stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock
proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor
and heat shock protein expression levels, and related them with war trauma
exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70
were determined by immunoblotting in lymphocytes from war trauma-exposed men with
current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD
group, n=61) and without PTSD (trauma control group, n=88), and from non
traumatized healthy controls (healthy control group, n=85). Between-group
differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed.
The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control
and healthy control groups. On the other hand, GR level was correlated only with
Hsp90 level, and this correlation was evident in current PTSD and trauma control
groups. In conclusion, PTSD and exposure to trauma are not related to changes in
lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in
corticosteroid receptors interaction with heat shock proteins.
PMID- 24355685
TI - The relationship between taste sensitivity to phenylthiocarbamide and anhedonia.
AB - It has been proposed that taste sensitivity to bitter compounds such as,
phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), represents a genetic
marker for an increased vulnerability to depressive illness. Previous
explorations of this idea have proven equivocal. This study refines and further
explores this idea by focusing specifically on anhedonia (diminished hedonic
capacity), a key symptom in some depressive illness, linked also with sensory
pleasure. It is hypothesized that diminished PTC taste sensitivity will be
associated with more general decrements in hedonic capacity (anhedonia). An
opportunity sample of 198 university students were assessed using paper strips
impregnated with PTC, the same participants also completed a widely used
assessment of hedonic capacity, the Snaith-Hamilton Pleasure Scale (SHAPS).
Hedonic capacity scores positively correlated with PTC taste sensitivity;
specifically, heightened hedonic capacity was associated with heightened
sensitivity to the bitter taste of PTC. Furthermore, modest differences were
observed between those least (non-tasters) and most (supertasters) sensitive to
PTC, with non-tasters reporting significantly lower hedonic capacity scores than
supertasters. PTC taste sensitivity may represent a peripheral risk factor for
anhedonia.
PMID- 24355686
TI - Sex differences in first-episode psychosis and in people at ultra-high risk.
AB - Sex-related differences in the clinical expression and outcome of schizophrenia
have long been recognized; this study set out to evaluate whether they extend to
those subjects who are at high risk of developing psychosis. In a sample enrolled
in two early intervention programs in northern Italy, patients with first-episode
psychosis (FEP; n=152) were compared to patients at ultra-high risk of psychosis
(UHR; n=106) on a series of sex-related clinical characteristics of
schizophrenia. In both the FEP and the UHR samples, males outnumbered females. In
FEP patients, women had been referred at an older age than men and had a shorter
duration of untreated illness (DUI) and of untreated psychosis. In UHR patients
no sex differences were found in age of onset or DUI. There was no diagnosis by
sex interaction on symptoms severity or level of functioning at presentation. The
limited number of women in both samples, and the exclusion of people who were
older than 30 and of those with substance dependence may have reduced the extent
of sex-related differences in this study. Sex differences of precipitating
factors for psychosis might be worthy of further investigation.
PMID- 24355687
TI - Fate of the naturally occurring radioactive materials during treatment of acid
mine drainage with coal fly ash and aluminium hydroxide.
AB - Mining of coal is very extensive and coal is mainly used to produce electricity.
Coal power stations generate huge amounts of coal fly ash of which a small amount
is used in the construction industry. Mining exposes pyrite containing rocks to
H2O and O2. This results in the oxidation of FeS2 to form H2SO4. The acidic
water, often termed acid mine drainage (AMD), causes dissolution of potentially
toxic elements such as, Fe, Al, Mn and naturally occurring radioactive materials
such as U and Th from the associated bedrock. This results in an outflow of AMD
with high concentrations of sulphate ions, Fe, Al, Mn and naturally occurring
radioactive materials. Treatment of AMD with coal fly ash has shown that good
quality water can be produced which is suitable for irrigation purposes. Most of
the potentially toxic elements (Fe, Al, Mn, etc) and substantial amounts of
sulphate ions are removed during treatment with coal fly ash. This research
endeavours to establish the fate of the radioactive materials in mine water with
coal fly ash containing radioactive materials. It was established that coal fly
ash treatment method was capable of removing radioactive materials from mine
water to within the target water quality range for drinking water standards. The
alpha and beta radioactivity of the mine water was reduced by 88% and 75%
respectively. The reduced radioactivity in the mine water was due to greater than
90% removal of U and Th radioactive materials from the mine water after treatment
with coal fly ash as ThO2 and UO2. No radioisotopes were found to leach from the
coal fly ash into the mine water.
PMID- 24355688
TI - Fragmentation patterns of evergreen oak woodlands in Southwestern Iberia:
identifying key spatial indicators.
AB - Mediterranean evergreen oak woodlands (composed of Quercus suber L. and Quercus
rotundifolia Lam.) are becoming increasingly fragmented in the human-modified
landscapes of Southwestern Portugal and Spain. Previous studies have largely
neglected to assess the spatial changes of oak woodlands in relation to their
surrounding landscape matrix, and to characterize and quantify woodland
boundaries and edges. The present study aims to fill this gap by analyzing
fragmentation patterns of oak woodlands over a 50-year period (1958-2007) in
three landscapes. Using archived aerial imagery from 1958, 1995 and 2007, for two
consecutive periods (1958-1995 and 1995-2007), we calculated a set of landscape
metrics to compare woodland fragmentation over time. Our results indicated a
continuous woodland fragmentation characterized by their edge dynamics. From 1958
to 2007, the replacement of open farmland by shrubland and by new afforestation
areas in the oak woodland landscape surrounding matrix, led to the highest values
for edge contrast length trends of 5.0 and 12.3, respectively. Linear
discriminant analysis was performed to delineate fragmented woodland structures
and identify metric variables that characterize woodland spatial configuration.
The edge contrast length with open farmland showed a strong correlation with F1
(correlations ranging between 0.55 and 0.98) and may be used as a proxy for oak
woodland mixedness in landscape matrix. The edge dynamics of oak woodlands may
result in different patterns of oak recruitment and therefore, its study may be
helpful in highlighting future baselines for the sustainable management of oak
woodlands.
PMID- 24355689
TI - Addressing structural and observational uncertainty in resource management.
AB - Most natural resource management and conservation problems are plagued with high
levels of uncertainties, which make good decision making difficult. Although some
kinds of uncertainties are easily incorporated into decision making, two types of
uncertainty present more formidable difficulties. The first, structural
uncertainty, represents our imperfect knowledge about how a managed system
behaves. The second, observational uncertainty, arises because the state of the
system must be inferred from imperfect monitoring systems. The former type of
uncertainty has been addressed in ecology using Adaptive Management (AM) and the
latter using the Partially Observable Markov Decision Processes (POMDP)
framework. Here we present a unifying framework that extends standard POMDPs and
encompasses both standard POMDPs and AM. The approach allows any system variable
to be observed or not observed and uses any relevant observed variable to update
beliefs about unknown variables and parameters. This extends standard AM, which
only uses realizations of the state variable to update beliefs and extends
standard POMDP by allowing more general stochastic dependence among the
observable variables and the state variables. This framework enables both
structural and observational uncertainty to be simultaneously modeled. We
illustrate the features of the extended POMDP framework with an example.
PMID- 24355690
TI - Left ventricular dimensions, systolic functions, and mass in term neonates with
symmetric and asymmetric intrauterine growth restriction.
AB - BACKGROUND: Previous studies have demonstrated structural changes in the heart
and cardiac dysfunction in foetuses with intrauterine growth restriction. There
are no available data that evaluated left ventricular dimensions and mass in
neonates with symmetric and asymmetric intrauterine growth restriction.
Therefore, we aimed to evaluate left ventricular dimensions, systolic functions,
and mass in neonates with symmetric and asymmetric intrauterine growth
restriction. We also assessed associated maternal risk factors, and compared
results with healthy appropriate for gestational age neonates. METHODS: In all,
62 asymmetric intrauterine growth restriction neonates, 39 symmetric intrauterine
growth restriction neonates, and 50 healthy appropriate for gestational age
neonates were evaluated by transthoracic echocardiography. RESULTS: The
asymmetric intrauterine growth restriction group had significantly lower left
ventricular end-systolic and end-diastolic diameters and posterior wall diameter
in systole and diastole than the control group. The symmetric intrauterine growth
restriction group had significantly lower left ventricular end-diastolic diameter
than the control group. All left ventricular dimensions were lower in the
asymmetric intrauterine growth restriction neonates compared with symmetric
intrauterine growth restriction neonates (p>0.05), but not statistically
significant except left ventricular posterior wall diameter in diastole (3.08+/
0.83 mm versus 3.54 +/-0.72 mm) (p<0.05). Both symmetric and asymmetric
intrauterine growth restriction groups had significantly lower relative posterior
wall thickness (0.54+/-0.19 versus 0.48+/-0.13 versus 0.8+/-0.12), left
ventricular mass (9.8+/-4.3 g versus 8.9+/-3.4 g versus 22.2+/-5.7 g), and left
ventricular mass index (63.6+/-29.1 g/m2 versus 54.5+/-24.4 g/m2 versus 109+/
28.8 g/m2) when compared with the control group. CONCLUSIONS: Our study has
demonstrated that although neonates with both symmetric and asymmetric
intrauterine growth restriction had lower left ventricular dimensions, relative
posterior wall thickness, left ventricular mass, and mass index when compared
with appropriate for gestational age neonates, left ventricular systolic
functions were found to be preserved. In our study, low socio-economic level,
short maternal stature, and low maternal weight were found to be risk factors to
develop intrauterine growth restriction. To our knowledge, our study is the first
to evaluate left ventricular dimensions, wall thicknesses, mass, and systolic
functions in neonates with intrauterine growth restriction and compare results
with respect to asymmetric or symmetric subgroups.
PMID- 24355691
TI - Is leptin a predictive factor in patients with lung cancer?
AB - OBJECTIVES: The aim of this study was to evaluate the expression and clinical
significance of leptin in lung cancer. METHODS: 126 patients with lung cancer
ranged from 30 to 83years of age were studied. Serum leptin levels were
determined by ELISA. The mRNA and protein levels of leptin in normal and lung
cancer tissues were measured by RT-PCR and immunohistochemistry. The
relationships between leptin levels and clinicopathological factors were
evaluated by Wilcoxon rank sum or Kruskal-Wallis H test. RESULTS: Serum leptin
levels in lung cancer patients were significantly higher compared to those in
controls and leptin expression in lung cancer tissue was markedly increased than
that in normal lung tissue (both P<0.050). CONCLUSIONS: Determination of leptin
levels might provide useful predictive information for lung cancer.
PMID- 24355692
TI - The chaperone role of the pyridoxal 5'-phosphate and its implications for rare
diseases involving B6-dependent enzymes.
AB - The biologically active form of the B6 vitamers is pyridoxal 5'-phosphate (PLP),
which plays a coenzymatic role in several distinct enzymatic activities ranging
from the synthesis, interconversion and degradation of amino acids to the
replenishment of one-carbon units, synthesis and degradation of biogenic amines,
synthesis of tetrapyrrolic compounds and metabolism of amino-sugars. In the
catalytic process of PLP-dependent enzymes, the substrate amino acid forms a
Schiff base with PLP and the electrophilicity of the PLP pyridine ring plays
important roles in the subsequent catalytic steps. While the essential role of
PLP in the acquisition of biological activity of many proteins is long
recognized, the finding that some PLP-enzymes require the coenzyme for refolding
in vitro points to an additional role of PLP as a chaperone in the folding
process. Mutations in the genes encoding PLP-enzymes are causative of several
rare inherited diseases. Patients affected by some of these diseases (AADC
deficiency, cystathionuria, homocystinuria, gyrate atrophy, primary hyperoxaluria
type 1, xanthurenic aciduria, X-linked sideroblastic anaemia) can benefit,
although at different degrees, from the administration of pyridoxine, a PLP
precursor. The effect of the coenzyme is not limited to mutations that affect the
enzyme-coenzyme interaction, but also to those that cause folding defects,
reinforcing the idea that PLP could play a chaperone role and improve the folding
efficiency of misfolded variants. In this review, recent biochemical and cell
biology studies highlighting the chaperoning activity of the coenzyme on folding
defective variants of PLP-enzymes associated with rare diseases are presented and
discussed.
PMID- 24355693
TI - Testosterone Deficiency Syndrome: an overview with emphasis on the diagnostic
conundrum.
AB - OBJECTIVES: To review the controversial issues of the Testosterone Deficiency
Syndrome (TDS) with an emphasis on the concerns about the diagnosis. DESIGN AND
METHODS: The relevant literature was reviewed with particular attention to
matters related to the clinical manifestations of the syndrome, the need for
biochemical assessment and questions of biological and analytical variation that
have to be taken into account. Therapeutic options were also appraised. RESULTS:
There are numerous difficulties with the clinical diagnosis of TDS due to the
lack of specificity and subtlety of the manifestations when the degree of
deficiency is not severe. Confirmation of the clinical impression requires
laboratory evaluation but the choice of assays remains an unsettled issue
although there is a general consensus that both free testosterone and
bioavailable testosterone best reflect the degree of androgenicity. The
laboratory diagnosis enjoys a great deal of credibility among clinicians but
shortcomings in the interpretation of the assays need to be reiterated and the
need for close collaboration between the clinician and the clinical biochemist is
important for diagnostic accuracy. Even when the clinical picture is convincing,
the laboratory may produce inconclusive results. The option of a therapeutic
trial should be contemplated in this situation. Treatment options should be
decided between the physician and the patient considering issues of availability,
tolerance, efficacy and cost. CONCLUSIONS: TDS is a prevalent condition but a
matter of persistent controversy due to the vagaries of the clinical and
laboratory diagnosis. Symptomatic men with documented T deficiency deserve
treatment to improve their quality of life.
PMID- 24355695
TI - Polyketide synthesis in tobacco plants transformed with a Plumbago zeylanica type
III hexaketide synthase.
AB - A type III polyketide synthase from Plumbago zeylanica (PzPKS) was cloned and
expressed in tobacco plants to study whether the transgenic tobacco plants
expressing PzPKS synthesize the pharmacologically important polyketide,
plumbagin. High resolution mass spectrometry based metabolite profiling of two
transgenic events and wild type tobacco plants was carried out to investigate
changes in polyketides, including plumbagin. Ten polyketides, which included six
pyrones and four naphthalene derivatives, were identified in PzPKS transgenic
plants. While one pyrone, styryl-2-pyranone, was detected in both, wild type and
transgenic tobacco plants, three pyrones were expressed only in the leaves of
transgenic tobacco plants. The transgenic tobacco plants did not accumulate
plumbagin, but showed accumulation of isoshinanolone in the roots, which is
postulated to be the reduction product of plumbagin. In addition, leaves of
transgenic tobacco plants accumulated 3-methyl-1,8-naphthalenediol, a postulated
precursor of plumbagin. The results indicated the requirement of additional
Plumbago-specific components in the biosynthetic pathway of this polyketide.
PMID- 24355694
TI - Clinical and prognostic role of circulating MMP-2 and its inhibitor TIMP-2 in HCC
patients prior to and after trans-hepatic arterial chemo-embolization.
AB - BACKGROUND AND AIMS: Trans-hepatic arterial chemo-embolization is the most
commonly used treatment for unresectable hepatocellular carcinoma. The prognostic
impact of tumor biomarkers has not therefore been evaluated in this treatment.
Imbalance between matrix metalloproteinase-2 and tissue inhibitor
metalloproteinase-2 is considered to play an important role in extracellular
matrix remodeling and degradation. Higher serum levels of MMP-2 have been shown
to predict a poor prognosis and shorter overall survival in HCC after TACE. The
objective of this study was to evaluate the serum levels of MMP-2 and TIMP-2 in
HCC patients before and after TACE to evaluate their clinical significance and
usefulness as prognostic biomarkers. METHODS: MMP-2 and TIMP-2 levels were
measured by ELISA in 75 HCC patients and 30 healthy controls. Sera MMP-2 and TIMP
2 were correlated with clinico-pathological features. RESULTS: The mean serum MMP
2 and TIMP-2 levels of HCC patients before TACE were 1700+/-71ng/mL and 89+/
45ng/mL respectively, significantly higher than that of the control group: 771+/
60ng/mL (p<0.0001, t-test) and 25.7+/-20ng/mL respectively (p<0.0001, t-test). A
significant decrease of MMP-2 levels after 1 and 3months compared to baseline
time was observed (p<0.0001), while with TIMP-2 a gradual increase in serum
before and after TACE (p<0.01) was detected. No significant correlation between
serum MMP-2 levels and other clinico-pathological features was observed. Patients
with serum MMP-2 >1500ng/mL (median value) had worse overall and recurrence-free
survival compared with those with serum MMP-2 levels <1500ng/mL before treatment.
CONCLUSION: Higher serum MMP-2 levels and MMP-2/TIMP-2 ratio could predict poor
prognosis after TACE, suggesting prognostic role of these biomarkers in HCC.
PMID- 24355696
TI - Alternative purification method for recombinant measles viral nucleoprotein
expressed in insect cells by ion-exchange chromatography.
AB - Recombinant measles virus nucleoproteins (rMeV N) and fusion (F) proteins were
characterized as major antigenic proteins expressed in insect cells mediated by
recombinant baculoviruses (rBVs). Band intensities were analyzed by Western
blotting to recognize IgG and IgM antibodies against the rMeV N and F proteins in
human sera and cerebrospinal fluids (CSFs) from patients with measles infections.
Positive results from the blots using the rMeV N were consistent with the results
of enzyme-linked immunosorbent assays (ELISAs) in which whole viral proteins were
used as antigens. Human sera and CSFs reacted more strongly with the rMeV N than
with the rMeV F proteins prepared in an identical expression system. For
efficient and reliable purification, ion-exchange chromatography using Source Q
anion resin was applied, and high-purity rMeV N protein was harvested. To
characterize the similarity with the native viral protein to purified N protein,
structural mimicry of purified recombinant proteins with intact rMeV N was shown
through transmission electron microscopy, and the truncation and the
phosphorylation status of the expressed protein were analyzed. These results
suggest that the rMeV N purified by ion-exchange chromatography has features
similar to those of naive N including a self-assembled structure, phosphorylation
and antigenic function. Thus, these expression and purification methods can be
applied to the large-scale production of the rMeV N, which is essential for the
development of new diagnostic tools and vaccines for acute and chronic MeV
infections.
PMID- 24355698
TI - Herbal teas and the continuum of the food-medicine complex: field methods,
contextualisation and cultural consensus.
PMID- 24355697
TI - Classification of small lesions on dynamic breast MRI: Integrating dimension
reduction and out-of-sample extension into CADx methodology.
AB - OBJECTIVE: While dimension reduction has been previously explored in computer
aided diagnosis (CADx) as an alternative to feature selection, previous
implementations of its integration into CADx do not ensure strict separation
between training and test data required for the machine learning task. This
compromises the integrity of the independent test set, which serves as the basis
for evaluating classifier performance. METHODS AND MATERIALS: We propose,
implement and evaluate an improved CADx methodology where strict separation is
maintained. This is achieved by subjecting the training data alone to dimension
reduction; the test data is subsequently processed with out-of-sample extension
methods. Our approach is demonstrated in the research context of classifying
small diagnostically challenging lesions annotated on dynamic breast magnetic
resonance imaging (MRI) studies. The lesions were dynamically characterized
through topological feature vectors derived from Minkowski functionals. These
feature vectors were then subject to dimension reduction with different linear
and non-linear algorithms applied in conjunction with out-of-sample extension
techniques. This was followed by classification through supervised learning with
support vector regression. Area under the receiver-operating characteristic curve
(AUC) was evaluated as the metric of classifier performance. RESULTS: Of the
feature vectors investigated, the best performance was observed with Minkowski
functional 'perimeter' while comparable performance was observed with 'area'. Of
the dimension reduction algorithms tested with 'perimeter', the best performance
was observed with Sammon's mapping (0.84+/-0.10) while comparable performance was
achieved with exploratory observation machine (0.82+/-0.09) and principal
component analysis (0.80+/-0.10). CONCLUSIONS: The results reported in this study
with the proposed CADx methodology present a significant improvement over
previous results reported with such small lesions on dynamic breast MRI. In
particular, non-linear algorithms for dimension reduction exhibited better
classification performance than linear approaches, when integrated into our CADx
methodology. We also note that while dimension reduction techniques may not
necessarily provide an improvement in classification performance over feature
selection, they do allow for a higher degree of feature compaction.
PMID- 24355699
TI - Improved resection in lesional temporal lobe epilepsy surgery using
neuronavigation and intraoperative MR imaging: favourable long term surgical and
seizure outcome in 88 consecutive cases.
AB - PURPOSE: To investigate the value of intraoperative MR imaging (iopMRI) combined
with neuronavigation to avoid intraoperative underestimation of the resection
amount during surgery of lesional temporal lobe epilepsy (LTLE) patients.
METHODS: We retrospectively investigated 88 patients (40 female, 48 male, mean
age 37.2 yrs, from 12 to 69 yrs, 41 left sided lesions) with LTLE operated at our
department, including 40.9% gangliogliomas (GG), 26.1% cavernomas (CM), 10.2%
dysembryoplastic neuroepithelial tumours (DNT) and 11.4% focal cortical
dysplasias (FCD), excluding hippocampal sclerosis. RESULTS: Complete resection
was achieved in 85 of 88 patients (96.6%), as proven by postoperative MRI 6
months after surgery. In contrast, the routine first iopMR imaging before closure
revealed radical resection in only 66 of these 88 patients (75%). After re
intervention, the second iopMR imaging demonstrated complete resection in 19 more
patients. Thus, as a direct effect of iopMRI and neuronavigation, overall
resection rate was increased by 21.6%. An excellent seizure outcome Engel Class I
was found in 76.1% of patients during a mean follow-up of 26.4 months,
irrespective of histological entity (74% in CM, 75% in GG, 78% in DNT and 60% in
FCD). No severe postoperative complications occurred; permanent superior visual
field defects were detected in 10.2% and permanent dysphasia/dyscalculia in 1.1%.
CONCLUSION: Refined surgery using neuronavigation combined with iopMR imaging in
LTLE surgery led to radical resection in 96.6% of the patients, due to immediate
correction of underestimated resection in 21.6% of patients. This protocol
resulted in a favourable seizure outcome and a low complication rate.
PMID- 24355700
TI - Utilization of care among drug resistant epilepsy patients with symptoms of
anxiety and depression.
AB - PURPOSE: Epilepsy patients have a significantly higher rate of anxiety and
depression than the general population, and psychiatric disease is particularly
prevalent among drug resistant epilepsy patients. Symptoms of anxiety and
depression might serve as a barrier to appropriate epilepsy care. The aim of this
study was to determine if drug resistant epilepsy patients with symptoms of
anxiety and/or depression receive different epilepsy management than controls.
METHOD: We identified 83 patients with drug resistant focal epilepsy seen at the
Penn Epilepsy Center. Upon enrollment, all patients completed 3 self-report
scales and a neuropsychiatric inventory and were grouped into those with symptoms
of anxiety and/or depression and controls. Each patient's medical records were
retrospectively reviewed for 1-2 years, and objective measures of outpatient and
inpatient epilepsy management were assessed. RESULTS: At baseline, 53% (n=43) of
patients screened positive for symptoms of anxiety and/or depression. The
remaining 47% (n=38) served as controls. Patients with anxiety and/or depression
symptoms had more missed outpatient visits per year compared to controls (median
0.84 vs. 0.48, p=0.02). Patients with symptoms of both anxiety and depression
were more likely to undergo an inpatient admission or procedure (56% vs. 24%,
p=0.02). CONCLUSION: For most measures of epilepsy management, symptoms of
anxiety and/or depression do not alter epilepsy care; however, drug resistant
epilepsy patients with anxiety and/or depression symptoms may be more likely to
miss outpatient appointments, and those with the highest burden of psychiatric
symptoms may be admitted more frequently for inpatient services compared to
controls.
PMID- 24355701
TI - Whooping cough in South-East Romania: a 1-year study.
AB - The incidence of whooping cough in Romania is substantially underestimated, and,
as noted by the health authorities, this is mostly due to the lack of both
awareness and biological diagnosis. We conducted a 1-year study in Bucharest in
order to assess the circulation of Bordetella pertussis, the main etiological
agent of whooping cough. Fifty-one subjects suspected of whooping cough were
enrolled. Culture, real-time PCR, and enzyme-linked immunosorbent assay were used
for laboratory diagnosis. Whooping cough patients (63%) were distributed among
all age groups, and most were unvaccinated, incompletely vaccinated, or had been
vaccinated more than 5 years previously. Bordetella holmesii DNA was detected in
22% of the bordetellosis cases; these patients included adults; teenagers; and,
surprisingly, young children. B. pertussis isolates were similar to the clinical
isolates currently circulating elsewhere in Europe. One isolate does not express
pertactin, an antigen included in some acellular pertussis vaccines.
PMID- 24355702
TI - Changes to level ground transtibial amputee gait with a weighted backpack.
AB - BACKGROUND: Many occupations and hobbies require the use of a weighted pack. To
date there has been limited backpack gait studies performed on the amputee
population. It is important that we address this knowledge gap in order to
further improve individual's quality of living through changes in rehabilitation,
and prosthesis development. METHODS: The study population was ten male,
unilateral, traumatic, K4-level (ability for prosthetic ambulation with high
impact, stress, or energy levels), transtibial amputees. Ten walking trials were
collected on level ground; five with a 24.5 kg backpack and five without a
backpack. Temporal-spatial parameters and kinematic and kinetic peak values for
the ankle, knee, hip, pelvis, and trunk were collected and analyzed for
significant differences. FINDINGS: Temporal-spatial parameters incurred changes
that were congruent with the literature on able bodied individuals. Pelvis speeds
and range of motion decreased with the pack. Knee flexion during weight
acceptance increased, and was supported on the intact limb by increased eccentric
knee power during weight acceptance. Hip flexion on both limbs also increased
during weight acceptance while wearing the backpack. INTERPRETATION: The backpack
load can be accommodated by people at a K4 functional level for level ground
walking. At the prosthetic limb, greater deformation was found at the foot-ankle
and further increases in pack weight and higher impact tasks (i.e., jogging)
could lead to decreased performance for some prosthetic feet. Gait training
programs should focus on removing any gait asymmetries and increasing the
strength of both the hip and knee flexors.
PMID- 24355703
TI - Mechanical properties of the human hand digits: age-related differences.
AB - BACKGROUND: Mechanical properties of human digits may have significant
implications for the hand function. We quantified several mechanical
characteristics of individual digits in young and older adults. METHODS: Digit
tip friction was measured at several normal force values using a method of
induced relative motion between the digit tip and the object surface. A modified
quick-release paradigm was used to estimate digit apparent stiffness, damping,
and inertial parameters. The subjects grasped a vertical handle instrumented with
force/moment sensors using a prismatic grasp with four digits; the handle was
fixed to the table. Unexpectedly, one of the sensors yielded leading to a quick
displacement of the corresponding digit. A second-order, linear model was used to
fit the force/displacement data. FINDINGS: Friction of the digit pads was
significantly lower in older adults. The apparent stiffness coefficient values
were higher while the damping coefficients were lower in older adults leading to
lower damping ratio. The damping ratio was above unity for most data in young
adults and below unity for older adults. Quick release of a digit led to force
changes in other digits of the hand, likely due to inertial hand properties.
These phenomena of "mechanical enslaving" were smaller in older adults although
no significant difference was found in the inertial parameter in the two groups.
INTERPRETATIONS: The decreased friction and damping ratio present challenges for
the control of everyday prehensile tasks. They may lead to excessive digit forces
and low stability of the grasped object.
PMID- 24355704
TI - Blood, sex and trust: The limits of the population-based risk management
paradigm.
AB - Blood screening is imperfect so Donor Health Check questionnaires (DHC) are used
to defer those whose 'behaviour' suggests disproportionate risk of Blood Borne
Infection (BBI). Taking the UK case, we compare deferment of three sub
populations with different HIV prevalence; Men-who-have-Sex-with-Men (4.7%),
black-Africans (3.7%) and 'the-general-(heterosexual)-population' (c.0.09%)
arguing that, with respect to STIs, DHC assesses risk based on broad population
level risk-groups not behaviour. This approach relies on an imaginative geography
that distances heterosexual risk from the domestic population. Most DHCs
knowingly commit the ecological fallacy allowing population-level statistics to
obscure within-group diversity, inadequately identifying the risk posed by 'low
risk-groups'. The disjuncture between ontological risk phenomenon (diverse sexual
practice) and the epistemological grid used to map risk (homogenised risk-groups)
needs examination. Unpacking the category 'heterosexual' would both better
differentiate risk within this group and change the relative-risk calculated for
'high-risk groups'. We call for piloting of practice-based questions and a mixed
method approach to DHCs to more accurately assess all potential donors.
PMID- 24355705
TI - Between self-clarity and recovery in schizophrenia: reducing the self-stigma and
finding meaning.
AB - Although there are extensive theoretical reviews regarding the self-experience
among persons with schizophrenia, there is limited research that addresses the
implications of self-clarity on the recovery of persons with schizophrenia while
exploring the role of possible mediators within this process. Accordingly, the
current study explored the relationship between self-clarity and recovery while
examining the possible mediating role of self-stigma and sense of meaning in
life. 80 persons with schizophrenia or schizoaffective disorder were administered
four scales: self-concept clarity, self-stigma, meaning in life, and recovery.
Results confirmed the hypothesized model in which self-clarity affects self
stigma, self-stigma affects meaning in life, and meaning in life affects
recovery. No direct relationship was uncovered between self-clarity and recovery.
Implications of the current study for future research and clinical practice are
discussed with the emphasis on the importance of the self-experience with regard
to the process of recovery.
PMID- 24355706
TI - Schizophrenia and the paranormal: more psi belief and superstition, and less deja
vu in medicated schizophrenic patients.
AB - OBJECTIVE: The present study examined the relation between deja vu experiences
and paranormal beliefs in schizophrenic patients. METHODS: A total of 522
participants (54.5% female; mean age=33.3, SD=16.02) were recruited, including
422 healthy adults (60.9% female; mean age=29.48, SD=15.07) and 100 medicated
adult schizophrenic patients (27.3% female; mean age=48.98, SD=8.57). The Chinese
version of the Inventory of Deja-vu Experiences Assessment was created via back
translation. Chinese versions of the Revised Paranormal Belief Scale (CRPB), Beck
Anxiety Inventory (CBAI), and Perceived Stress Scale (CPSS) were also used.
RESULTS AND CONCLUSION: After controlling for age, gender, education, and
anxiety, the results supported the following three hypotheses. Schizophrenic
persons have fewer deja vu experiences than normal persons. These experiences are
positively related to paranormal beliefs in healthy adults but not in
schizophrenic patients. Schizophrenic patients have higher scores than healthy
adults on the psi and superstitious subscales of the CRPB.
PMID- 24355707
TI - The year in review.
PMID- 24355709
TI - Thymosin beta 4 gene silencing decreases stemness and invasiveness in
glioblastoma.
AB - Thymosin beta 4 is a pleiotropic actin-sequestering polypeptide that is involved
in wound healing and developmental processes. Thymosin beta 4 gene silencing
promotes differentiation of neural stem cells whereas thymosin beta 4
overexpression initiates cortical folding of developing brain hemispheres. A role
of thymosin beta 4 in malignant gliomas has not yet been investigated. We
analysed thymosin beta 4 staining on tissue microarrays and performed
interrogations of the REMBRANDT and the Cancer Genome Atlas databases. We
investigated thymosin beta 4 expression in seven established glioma cell lines
and seven glioma-initiating cell lines and induced or silenced thymosin beta 4
expression by lentiviral transduction in LNT-229, U87MG and GS-2 cells to study
the effects of altered thymosin beta 4 expression on gene expression, growth,
clonogenicity, migration, invasion, self-renewal and differentiation capacity in
vitro, and tumorigenicity in vivo. Thymosin beta 4 expression increased with
grade of malignancy in gliomas. Thymosin beta 4 gene silencing in LNT-229 and
U87MG glioma cells inhibited migration and invasion, promoted starvation-induced
cell death in vitro and enhanced survival of glioma-bearing mice. Thymosin beta 4
gene silencing in GS-2 cells inhibited self-renewal and promoted differentiation
in vitro and decreased tumorigenicity in vivo. Gene expression analysis suggested
a thymosin beta 4-dependent regulation of mesenchymal signature genes and
modulation of TGFbeta and p53 signalling networks. We conclude that thymosin beta
4 should be explored as a novel molecular target for anti-glioma therapy.
PMID- 24355708
TI - PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a
broad neurodegenerative spectrum.
AB - Boucher-Neuhauser and Gordon Holmes syndromes are clinical syndromes defined by
early-onset ataxia and hypogonadism plus chorioretinal dystrophy (Boucher
Neuhauser syndrome) or brisk reflexes (Gordon Holmes syndrome). Here we uncover
the genetic basis of these two syndromes, demonstrating that both clinically
distinct entities are allelic for recessive mutations in the gene PNPLA6. In five
of seven Boucher-Neuhauser syndrome/Gordon Holmes syndrome families, we
identified nine rare conserved and damaging mutations by applying whole exome
sequencing. Further, by dissecting the complex clinical presentation of Boucher
Neuhauser syndrome and Gordon Holmes syndrome into its neurological system
components, we set out to analyse an additional 538 exomes from families with
ataxia (with and without hypogonadism), pure and complex hereditary spastic
paraplegia, and Charcot-Marie-Tooth disease type 2. We identified four additional
PNPLA6 mutations in spastic ataxia and hereditary spastic paraplegia families,
revealing that Boucher-Neuhauser and Gordon Holmes syndromes in fact represent
phenotypic clusters on a spectrum of neurodegenerative diseases caused by
mutations in PNPLA6. Structural analysis indicates that the majority of mutations
falls in the C-terminal phospholipid esterase domain and likely inhibits the
catalytic activity of PNPLA6, which provides the precursor for biosynthesis of
the neurotransmitter acetylcholine. Our findings show that PNPLA6 influences a
manifold of neuronal systems, from the retina to the cerebellum, upper and lower
motor neurons and the neuroendocrine system, with damage of this protein causing
an extraordinarily broad continuous spectrum of associated neurodegenerative
disease.
PMID- 24355710
TI - Rewiring of the corticospinal tract in the adult rat after unilateral stroke and
anti-Nogo-A therapy.
AB - Adult Long Evans rats received a photothrombotic stroke that destroyed >90% of
the sensorimotor cortex unilaterally; they were subsequently treated
intrathecally for 2 weeks with a function blocking antibody against the neurite
growth inhibitory central nervous system protein Nogo-A. Fine motor control of
skilled forelimb grasping improved to 65% of intact baseline performance in the
anti-Nogo-A treated rats, whereas control antibody treated animals recovered to
only 20% of baseline scores. Bilateral retrograde tract tracing with two
different tracers from the intact and the denervated side of the cervical spinal
cord, at different time points post-lesion, indicated that the intact
corticospinal tract had extensively sprouted across the midline into the
denervated spinal hemicord. The original axonal arbours of corticospinal tract
fibres that had recrossed the midline were subsequently withdrawn, leading to a
complete side-switch in the projection of a subpopulation of contralesional
corticospinal tract axons. Anterograde tracing from the contralesional cortex
showed a 2-3-fold increase of midline crossing fibres and additionally a massive
sprouting of the pre-existing ipsilateral ventral corticospinal tract fibres
throughout the entire cervical enlargement of the anti-Nogo-A antibody-treated
rats compared to the control group. The laminar distribution pattern of the
ipsilaterally projecting corticospinal tract fibres was similar to that in the
intact spinal cord. These plastic changes were paralleled by a somatotopic
reorganization of the contralesional motor cortex where the formation of an
ipsilaterally projecting forelimb area was observed. Intracortical
microstimulation of the contralesional motor cortex revealed that low threshold
currents evoked ipsilateral movements and electromyography responses at frequent
cortical sites in the anti-Nogo-A, but not in the control antibody-treated
animals. Subsequent transection of the spared corticospinal tract in chronically
recovered animals, treated with anti-Nogo-A, led to a reappearance of the initial
lesion deficit observed after the stroke lesion. These results demonstrate a
somatotopic side switch anatomically and functionally in the projection of adult
corticospinal neurons, induced by the destruction of one sensorimotor cortex and
the neutralization of the CNS growth inhibitory protein Nogo-A.
PMID- 24355711
TI - Can the dual-functional capability of CIK cells be used to improve antitumor
effects?
AB - Cytokine-induced killer (CIK) cells, which display both potent anti-tumor ability
of T lymphocytes and non-major histocompatibility complex (MHC) restricted
killing tumor cells capacity of natural killer (NK) cells are capable of
recognizing and lysing a broad array of tumor targets. They have begun to be used
in clinical care with good prospects for treatment success. CIK cells are a
heterogeneous cell population that contain CD3(+)CD56(+) cells, CD3(-)CD56(+)
natural killer (NK) cells and CD3(+)CD56(-) T cells on which much attention has
been focused. This review will summarize the connections and differences among
CD3(+)CD56(+)CIK cells, CD3(-)CD56(+) NK cells and CD3(+)CD56(-) T cells in the
following aspects: the main cell surface molecule, killing mechanism, and
clinical applications so that treatment with CIK cells can be optimized and
further to enhance the antitumor effect.
PMID- 24355712
TI - Mutated HLA-G3 localizes to the cell surface but does not inhibit cytotoxicity of
natural killer cells.
AB - HLA-G plays an important role in the induction of immune tolerance. Various
attempts to produce good manufacturing practice levels of HLA-G as a therapeutic
molecule have failed to date partly due to the complicated structure of full
length HLA-G1. Truncated HLA-G3 is simpler and easier to produce than HLA-G1 and
contains the expected functional epitope in its only alpha1 monomorphic domain.
In this study, we engineered the ER retrieval and retention signal on HLA-G3's
cytoplasmic tail by replacing its RKKSSD motif with RAASSD. We observed that
mutated HLA-G3 was highly expressed on the cell surface of transduced K562 cells
but did not inhibit cytotoxicity of natural killer cells.
PMID- 24355713
TI - Socially disadvantaged women's views of barriers to feeling safe to engage in
decision-making in maternity care.
AB - BACKGROUND: Although midwifery literature suggests that woman-centred care can
improve the birthing experiences of women and birth outcomes for women and
babies, recent research has identified challenges in supporting socially
disadvantaged women to engage in decision-making regarding care options in order
to attain a sense of control within their maternity care encounters. OBJECTIVE:
The objective of this paper is to provide an understanding of the issues that
affect the socially disadvantaged woman's ability to actively engage in decision
making processes relevant to her care. RESEARCH DESIGN: The qualitative approach
known as Interpretative Phenomenological Analysis was used to gain an
understanding of maternity care encounters as experienced by each of the
following cohorts: socially disadvantaged women, registered midwives and student
midwives. This paper focuses specifically on data from participating socially
disadvantaged women that relate to the elements of woman-centred care-choice and
control and their understandings of capacity to engage in their maternity care
encounters. FINDINGS: Socially disadvantaged women participants did not feel safe
to engage in discussions regarding choice or to seek control within their
maternity care encounters. Situations such as inadequate contextualised
information, perceived risks in not conforming to routine procedures, and the
actions and reactions of midwives when these women did seek choice or control
resulted in a silent compliance. This response was interpreted as a consequence
of women's decisions to accept responsibility for their baby's wellbeing by
delegating health care decision-making to the health care professional.
CONCLUSION: This research found that socially disadvantaged women want to engage
in their care. However without adequate information and facilitation of choice by
midwives, they believe they are outsiders to the maternity care culture and
decision-making processes. Consequently, they delegate responsibility for
maternity care choices to those who do belong; midwives. These findings suggest
that midwives need to better communicate a valuing of the woman's participation
in decision-making processes and to work with women so they do have a sense of
belonging within the maternity care environment. Midwives need to ensure that
socially disadvantaged women do feel safe about having a voice regarding their
choices and find ways to give them a sense of control within their maternity care
encounters.
PMID- 24355714
TI - Proteomic analysis and immune properties of exosomes released by macrophages
infected with Mycobacterium avium.
AB - The role of exosomes shed from Mycobacterium avium sp. paratuberculosis-infected
macrophages in intercellular communication processes was examined. We compared
the responses of resting macrophages infected with M. avium sp. paratuberculosis
with those of resting macrophages treated with exosomes previously released from
macrophages infected with M. avium sp. paratuberculosis. Some proteins components
of exosomes released from resting macrophages infected with M. avium sp.
paratuberculosis showed a significantly differential expression compared with
exosomes from uninfected-macrophages. Both M. avium sp. paratuberculosis and
exosomes from infected-cells enhanced the expression of CD80 and CD86 and the
secretion of TNF-alpha and IFN-gamma by macrophages. This suggests that exosomes
from infected macrophages may be carriers of molecules, e.g. bacterial antigens
and/or components from infected macrophages, that can elicit responses in resting
cells. Two-dimensional analysis of the proteins present in exosomes from M. avium
sp. paratuberculosis-infected macrophages compared with those from resting cells
resulted in the identification by MALDI-TOF/TOF mass spectrometry of the
following differentially expressed proteins: two actin isoforms, guanine
nucleotide-binding protein beta-1, cofilin-1 and peptidyl-prolyl cis-trans
isomerase A. The possible relevance of the changes observed and the biological
functions of the proteins differentially present are discussed.
PMID- 24355716
TI - Simplified and safe method of sutureless intrascleral posterior chamber
intraocular lens fixation: Y-fixation technique.
AB - We report a new surgical technique that allows intrascleral fixation of a
posterior chamber intraocular lens (IOL) without sutures. The Y-fixation
technique does not involve complicated intraocular manipulation and achieves safe
sutureless fixation. A Y-shaped incision is made in the sclera and a 24-gauge
microvitreoretinal (MVR) knife is used to create the sclerotomy instead of a
needle. The Y-shaped incision eliminates the need to raise a large lamellar
scleral flap and to use fibrin glue because the haptic can be fixed both inside
the tunnel and in the groove, and performing the sclerotomy with the 24-gauge MVR
knife simplifies extraction of the haptic and improves wound closure. There is no
risk of infection from exposure of the haptic on the sclera and no use of fibrin
glue. There was significantly less IOL decentration and tilt than with suture
fixation.
PMID- 24355717
TI - Bean-shaped ring segments for capsule stretching and centration of bag-in-the
lens cataract surgery.
AB - The bag-in-the-lens (BIL) is a unique approach to IOL placement in cataract
surgery. The BIL intraocular lens (IOL) is suspended centrally, supported by the
anterior and posterior capsulorhexes. The placement confers a high degree of
centration and stability; however, it is dependent on capsular and zonular
integrity. In this report, we describe a patient with posttraumatic cataract
featuring a sector of iris and suspensory zonule loss. The insertion of custom
designed bean-shaped segments provides capsular tension over the area of defect
and a central aperture designed to support the BIL IOL.
PMID- 24355718
TI - Minimum amount of astigmatism that should be corrected.
AB - PURPOSE: To evaluate how small amounts of astigmatism affect visual acuity and
the minimum astigmatism values that should be corrected to achieve maximum visual
performance. SETTING: Optics Laboratory, University of Murcia, Murcia, Spain.
DESIGN: Case series. METHODS: A wavefront sensor was used to measure astigmatism
and higher-order aberrations (HOAs) in normal young eyes with astigmatism ranging
from 0.0 to 0.5 diopter (D). Astigmatism was corrected for natural pupil
diameters using a purpose-designed cross-cylinder device. Visual acuity was
measured for high-contrast and low-contrast stimuli at best subjective focus with
the natural and corrected astigmatism. From the aberrations, optical image
quality metrics were calculated for 3 conditions: natural astigmatism, corrected
astigmatism, and astigmatism only (with all HOAs removed). RESULTS: The study
evaluated 54 eyes. There was no significant correlation between the amount of
astigmatism and visual acuity. The correction of astigmatism improved visual
acuity for only high-contrast letters from 0.3 D, but with a high variability
between subjects. Low-contrast visual acuity changed randomly as astigmatism was
corrected. The correction of astigmatism increased the mean image-quality values;
however, there was no significant correlation with visual performance. The
deterioration in image quality given by astigmatism higher than 0.3 D was limited
by HOAs. CONCLUSIONS: In most subjects, astigmatism less than 0.5 D did not
degrade visual acuity. This suggests that under clinical conditions, the visual
benefit of precise correction of astigmatism less than 0.5 D would be limited.
PMID- 24355719
TI - Complications of femtosecond laser-assisted cataract surgery.
AB - PURPOSE: To analyze complications of femtosecond lasers used for cataract
surgery. SETTING: Department of Ophthalmology Semmelweis University, Budapest,
Hungary. DESIGN: Retrospective analysis. METHODS: Intraoperative complications of
the first 100 femtosecond laser-assisted (Alcon-Lensx, Inc.) cataract surgeries
were collected. Possible complications of femtosecond capsulotomies and their
management were also assessed. RESULTS: The complications were as follows:
suction break (2%), conjunctival redness or hemorrhage (34%), capsule tags and
bridges (20%), anterior tear (4%), miosis (32%), and endothelial damage due to
cut within the endothelial layer (3%). There were no cases of capsule blockage or
posterior capsule tear. During the learning curve, there was no complication that
would require vitrectomy. All complications occurred during the first 100 cases.
CONCLUSIONS: Femtosecond laser cataract surgery had a learning curve during the
first 100 cases. With cautious surgical technique, the complications can be
avoided. The femtosecond laser-assisted method was efficient and safe for
cataract surgery.
PMID- 24355720
TI - Clinical outcomes after bilateral implantation of an apodized +3.0 D toric
diffractive multifocal intraocular lens.
AB - PURPOSE: To assess visual outcomes after bilateral implantation of an apodized
+3.0 diopter (D) addition power toric diffractive multifocal intraocular lens
(IOL). SETTING: Five study sites in Europe and South America. DESIGN: Cohort
study. METHODS: Patients had bilateral implantation of the AcrySof((r)) IQ
ReSTOR((r))+3.0 D toric multifocal IOL. Inclusion criteria were age from 21 to 70
years, need for bilateral cataract extraction or refractive lens exchange, and
regular corneal astigmatism from 0.75 to 2.5 D. Six-month evaluations included
spherical equivalent (SE), refractive and corneal cylinder, visual acuity at
various distances, defocus testing, reading speed, and IOL rotation. RESULTS:
Forty-four of 49 patients completed the 6-month visit. The mean SE (88 eyes) was
0.09 D +/- 0.49 (SD) at 6 months (+/- 1.00 D in 95.2%). The mean refractive
cylinder decreased from 1.07 +/- 0.71 D to 0.33 +/- 0.44 D (<= 0.50 D in 78.6%
and <= 1.00 D in 92.9%). The mean binocular uncorrected visual acuity was 0.04 +/
0.08 logMAR at preferred near (~ 39 cm), 0.07 +/- 0.09 logMAR at 40 cm, 0.09 +/-
0.11 logMAR at 60 cm, and 0.05 +/- 0.10 logMAR at 4 m. The mean corrected reading
speed increased from 125.43 +/- 33.58 words per minute (wpm) to 132.68 +/- 23.69
wpm. The mean IOL rotation was 2.20 +/- 4.34 degrees. CONCLUSION: Six months
after implantation of the toric multifocal IOL, patients had significantly
reduced SE and refractive cylinder, good visual acuity across distances,
increased reading speed, and minimal IOL rotation.
PMID- 24355721
TI - Outcomes of a new diffractive trifocal intraocular lens.
AB - PURPOSE: To evaluate refractive and visual parameters related to distance,
intermediate, and near vision after cataract surgery and the optical quality of a
new diffractive trifocal intraocular lens (IOL). SETTING: Vissum Instituto
Oftalmologico de Alicante, Alicante, Spain. DESIGN: Case series. METHODS:
Patients had bilateral refractive lens exchange and multifocal diffractive IOL
(AT Lisa tri 839 MP) implantation. A complete ophthalmology examination was
performed preoperatively and postoperatively. The follow-up was 6 months. The
main outcome measures were uncorrected distance (UDVA) and corrected distance
(CDVA), intermediate, and near visual acuities; keratometry; manifest refraction;
and aberrations (total, corneal, internal). RESULTS: The study comprised 60 eyes
of 30 patients (mean age 57.9 years +/- 7.8 [SD]; range 42 to 76 years). There
was significant improvement in UDVA, uncorrected intermediate visual acuity,
uncorrected near visual acuity, CDVA, and distance-corrected intermediate and
near visual acuity. The postoperative refractive status was within the range of
+1.00 to -1.00 diopter. Total internal aberrations decreased significantly
(P<.001). CONCLUSIONS: The trifocal IOL improved near, intermediate, and distance
vision in presbyopic patients. The use of 3 foci provided significant
intermediate visual results without sacrificing near or distance vision.
PMID- 24355722
TI - Evaluation of the impact of light scatter from glistenings in pseudophakic eyes.
AB - PURPOSE: To study the impact of light scatter from glistenings in pseudophakic
eyes using ray tracing in a model eye SETTING: Department of Research, Advanced
Vision Science, Inc., Goleta, California, USA. DESIGN: Mathematical modeling and
simulation. METHODS: A pseudophakic eye model was constructed in Zemax using the
Arizona eye model as the basis. The Mie scattering theory was used to describe
the intensity and direction of light as it scatters for a spherical particle
immersed in a given media (intraocular lens [IOL]). The modeling and evaluation
of scatter and modulation transfer function (MTF) were performed for several
biomaterials with various size and density of glistenings under scotopic,
mesopic, and photopic conditions. RESULTS: As predicted by the Mie theory, the
amount of scatter was a function of the relative difference in refractive index
between the media and the scatterer, the size of the scatterer, and the volume
fraction of the scatterer. The simulation demonstrated that an increase in
density of glistenings can lead to a significant drop in the MTF of the IOL and
the pseudophakic eye. This effect was more pronounced in IOLs with smaller
cavitations, and the observation was consistent for all tested biomaterials.
CONCLUSIONS: Mathematical modeling demonstrated that glistenings in IOLs will
lead to reduction in the MTF of the IOL and the pseudophakic eye. The loss in MTF
was more pronounced at high densities and small cavitation sizes across all
biomaterials. Inconsistent and poor clinical quantification of glistenings in
IOLs may explain some inconsistencies in the literature.
PMID- 24355723
TI - Optical performance of hydrophobic acrylic intraocular lenses with surface light
scattering.
AB - PURPOSE: To evaluate the potential effect of surface light scattering on the
optical performance of hydrophobic acrylic intraocular lenses (IOLs) made of
Acrysof material. SETTING: Alcon Laboratories, Inc., Fort Worth, Texas, USA.
DESIGN: Experimental study. METHODS: Explanted IOLs from cadaver eyes with more
than 50 computer-compatible tape (CCT) units of scatter were selected, yielding 7
IOLs. Clinically explanted IOLs (n = 4) were obtained after IOLs had been
implanted 8.5 to 10.5 years. Explanted IOLs were matched to unused control IOLs.
After proteins were removed, scatter was measured for IOLs dry, wetted (2 minutes
in a balanced salt solution), and hydrated (24 hours). Badal imaging, ultraviolet
visible transmission, and modulation transfer function (MTF) measurements were
performed with hydrated IOLs. RESULTS: Hydrated scatter values ranged from 80 to
221 CCT for explanted IOLs and 2 to 7 CCT for controls. No differences in Badal
image resolution were observed between explanted IOLs and controls. The mean MTF
values at 100 line pairs per mm (representing 20/20 visual acuity) were similar
between explanted IOLs and controls. Over the range of 400 to 700 nm, a small
reduction (mean 2.1% +/- 1.4% [SD]) in transmission was observed. CONCLUSIONS:
Surface light scattering of explanted IOLs did not affect image resolution or MTF
values. Although light transmission was slightly decreased, the magnitude
appeared to be inconsequential for optical performance.
PMID- 24355724
TI - Light scattering and light transmittance of cadaver eye-explanted intraocular
lenses of different materials.
AB - PURPOSE: To evaluate light scattering and light transmittance in cadaver eye
explanted intraocular lenses (IOLs) manufactured from different materials.
SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.
DESIGN: Experimental study. METHODS: Forty-nine pseudophakic cadaver eyes were
selected according to IOL material/type and implantation duration, and the IOLs
were explanted. Hydrophobic acrylic, hydrophilic acrylic, poly(methyl
methacrylate) (PMMA), and silicone IOLs were included. Gross and light microscopy
was performed for all IOLs. Light scattering was measured with an EAS 1000
Scheimpflug camera, and light transmittance was assessed using a Lambda 35 UV/Vis
spectrophotometer (single-beam configuration with an RSA PE-20 integrating
sphere). Analyses were performed at room temperature in the hydrated state and
compared with analyses of controls. RESULTS: The highest levels of surface light
scattering were measured for 3-piece hydrophobic acrylic, which was also the IOL
type with the longest implantation duration among the Acrysof hydrophobic acrylic
IOLs. Hydrophilic acrylic, PMMA, and silicone IOLs exhibited relatively low light
scattering levels. The lowest light-scattering levels were observed with PMMA
IOLs (1-piece looped and 3-piece) and plate silicone IOLs, which represent the
IOL types with the longest implantation duration in this series. Light
transmittance values measured for all IOL types appeared to be similar to the
values of the corresponding control IOLs. CONCLUSIONS: The phenomenon of surface
light scattering (nanoglistenings) is more particularly related to hydrophobic
acrylic IOLs and increases with implantation time. No significant effect of
surface light scattering on IOL light transmittance was found.
PMID- 24355725
TI - Adoption of intracameral antibiotic prophylaxis of endophthalmitis following
cataract surgery: update on the ESCRS Endophthalmitis Study.
AB - To determine the use of intracameral cefuroxime at the end of cataract surgery
since the beneficial results were first reported by the European Society of
Cataract and Refractive Surgeons Endophthalmitis Study Group in 2006, 250
ophthalmic surgeons affiliated with both public and private hospitals and clinics
across Europe were surveyed. The questions regarded their awareness of the
results of the ESCRS endophthalmitis study and their current use or non-use of
intracameral antibiotics in their cataract procedures. Seventy-four percent of
respondents said they always or usually use intracameral antibiotics in their
cataract surgery procedures. The most frequently cited reasons for not using
cefuroxime or other intracameral antibiotics was the lack of an approved
commercial preparation and related anxieties regarding the risk of dilution
errors and contamination. More than 90% of respondents said they would use
cefuroxime if an approved single-unit dose product were commercially available.
PMID- 24355726
TI - Combined corneal collagen crosslinking and secondary intraocular lens
implantation for keratectasia after radial keratotomy.
AB - We describe a case of corneal ectasia in a patient with previous radial
keratotomy (RK). The uncorrected distance visual acuity (UDVA) was 20/400, the
corrected visual acuity (CDVA) 20/50, and the spherical equivalent (SE) -5.125
diopters (D). Corneal topography revealed inferior corneal ectasia with corneal
astigmatism of 9.2 D. Six months after corneal collagen crosslinking (CXL), the
UDVA improved to 20/200, the CDVA to 20/40, and the SE to -4.625 D. Corneal
astigmatism was reduced to 8.7 D. An add-on IOL was implanted to correct the
residual cylindrical refractive error (-9.25 * 60; Torica-sPB IOL, Humanoptics),
after which the UDVA improved to 20/32, the CDVA to 20/30, and the SE to -0.50 D.
This case is the first to document the efficacy of CXL in corneal ectasia as a
complication of primary RK in a nonkeratoconic or a keratoconus-suspect eye with
an add-on IOL used to correct the residual refractive error.
PMID- 24355727
TI - Capsulorhexis phimosis with anterior flexing of an accommodating IOL: case report
and histopathological analyses.
AB - We describe the case of a patient who had cataract surgery with implantation of
an accommodating hydrophilic acrylic intraocular lens (IOL) that exhibited
capsulorhexis phimosis and in-the-bag IOL luxation leading to explantation of the
IOL-capsular bag complex 10 years after implantation. Constriction of the
capsular bag secondary to fibrosis caused significant anterior flexing of the
haptic elements of the IOL. Histopathological analysis revealed dense anterior
subcapsular fibrosis and fibrous metaplasia of the anterior lens epithelial
cells. No signs suggestive of pseudoexfoliation were found. This case raises
concerns related to the continuously evolving indications for implantation of
accommodating and other highly flexible IOLs (eg, microincision IOLs),
particularly in patients with no clear predisposition to zonular weakness and,
accordingly, excessive capsular bag contraction.
PMID- 24355728
TI - Femtosecond laser-assisted capsulotomy after penetrating injury of the cornea and
lens capsule.
AB - We present a 39-year-old patient with a penetrating injury of the cornea and
anterior lens capsule containing an intralenticular foreign body. One week after
the accident, the patient consulted our emergency unit. Clinical examination
showed no Seidel II phenomenon. A femtosecond laser-assisted capsulotomy was
performed followed by lens removal and intraocular lens implantation. The
capsulotomy diameter was increased to 6.7 mm to include the foreign-body area and
the break in the anterior capsule. The procedure was uneventful, and the capsule
leaf, including the foreign body, was extracted safely.
PMID- 24355729
TI - Benefits of the European Registry of Quality Outcomes for Cataract and Refractive
Surgery to an ophthalmology trainee: how an ophthalmology trainee used EUREQUO to
audit their surgical training.
PMID- 24355730
TI - Qualitative analysis of Web-based refractive surgery information sessions.
PMID- 24355731
TI - January consultation # 2.
PMID- 24355732
TI - Glaucoma surgical problem: January consultation # 1.
PMID- 24355733
TI - January consultation # 4.
PMID- 24355734
TI - January consultation # 3.
PMID- 24355735
TI - January consultation # 6.
PMID- 24355736
TI - January consultation # 5.
PMID- 24355737
TI - January consultation # 7.
PMID- 24355738
TI - Reply: To PMID 23692885.
PMID- 24355739
TI - Intracameral steroids versus subconjunctival and systemic steroids: prevention of
postoperative inflammation in cataract with anterior uveitis.
PMID- 24355740
TI - Lateral canthotomy for femtosecond laser-assisted cataract surgery in infants.
PMID- 24355741
TI - Reply: To PMID 23608565.
PMID- 24355742
TI - Flawed culture method in povidone-iodine cataract surgery prep study.
PMID- 24355743
TI - Reply: To PMID 23680628.
PMID- 24355744
TI - Safety of extended use of hypoosmolar riboflavin in crosslinking.
PMID- 24355745
TI - Child mortality patterns in rural Tanzania: an observational study on the impact
of malaria control interventions.
AB - BACKGROUND: Between 1997 and 2009, a number of key malaria control interventions
were implemented in the Kilombero and Ulanga Districts in south central Tanzania
to increase insecticide-treated nets (ITN) coverage and improve access to
effective malaria treatment. In this study we estimated the contribution of these
interventions to observed decreases in child mortality. METHODS: The local Health
and Demographic Surveillance Site (HDSS) provided monthly estimates of child
mortality rates (age 1 to 5 years) expressed as cases per 1000 person-years
(c/1000py) between 1997 and 2009. We conducted a time series analysis of child
mortality rates and explored the contribution of rainfall and household food
security. We used Poisson regression with linear and segmented effects to explore
the impact of malaria control interventions on mortality. RESULTS: Child
mortality rates decreased by 42.5% from 14.6 c/1000py in 1997 to 8.4 c/1000py in
2009. Analyses revealed the complexity of child mortality patterns and a strong
association with rainfall and food security. All malaria control interventions
were associated with decreases in child mortality, accounting for the effect of
rainfall and food security. CONCLUSIONS: Reaching the fourth Millenium
Development Goal will require the contribution of many health interventions, as
well as more general improvements in socio-environmental and nutritional
conditions. Distinguishing between the effects of these multiple factors is
difficult and represents a major challenge in assessing the effect of routine
interventions. However, this study suggests that credible estimates can be
obtained when high-quality data on the most important factors are available over
a sufficiently long time period.
PMID- 24355746
TI - Measures of socioeconomic position are not consistently associated with ethnic
differences in cardiovascular disease in Scotland: methods from the Scottish
Health and Ethnicity Linkage Study (SHELS).
AB - BACKGROUND: Ethnic health inequalities are substantial. One explanation relates
to socioeconomic differences between groups. However, socioeconomic variables
need to be comparable across ethnic groups as measures of socioeconomic position
(SEP) and indicators of health outcomes. METHODS: We linked self-reported SEP and
ethnicity data on 4.65 million individuals from the 2001 Scottish Census to
hospital admission and mortality data for cardiovascular disease (CVD). We
examined the direction, strength and linearity of association between eight
individual, household and area socioeconomic measures and CVD in 10 ethnic groups
and the impact of SEP adjustment. RESULTS: There was wide socioeconomic variation
between groups. All eight measures showed consistent, positive associations with
CVD in White populations, as did educational qualification in non-White ethnic
groups. For other SEP measures, associations tended to be consistent with those
of White groups though there were one or two exceptions in each non-White group.
Multiple SEP adjustment had little effect on relative risk of CVD for most
groups. Where it did, the effect varied in direction and magnitude (for example
increasing adjusted risk by 23% in Indian men but attenuating it by 11% among
Pakistani women). CONCLUSIONS: Across groups, SEP measures were inconsistently
associated with CVD hospitalization or death, with effect size and direction of
effect after adjustment varying across ethnic groups. We recommend that
researchers systematically explore the effect of their choice of SEP indicators,
using standard multivariate methods where appropriate, to demonstrate their cross
ethnic group validity as potential confounding variables for the specific groups
and outcomes of interest.
PMID- 24355747
TI - The Arabidopsis thaliana GRF-INTERACTING FACTOR gene family plays an essential
role in control of male and female reproductive development.
AB - Reproductive success of angiosperms relies on the precise development of the
gynoecium and the anther, because their primary function is to bear and to
nurture the embryo sac/female gametophyte and pollen, in which the egg and sperm
cells, respectively, are generated. It has been known that the GRF-INTERACTING
FACTOR (GIF) transcription co-activator family of Arabidopsis thaliana
(Arabidopsis) consists of three members and acts as a positive regulator of cell
proliferation. Here, we demonstrate that GIF proteins also play an essential role
in development of reproductive organs and generation of the gamete cells. The
gif1 gif2 gif3 triple mutant, but not the single or double mutants, failed to
establish normal carpel margin meristem (CMM) and its derivative tissues, such as
the ovule and the septum, resulting in a split gynoecium and no observable embryo
sac. The gif triple mutant also displayed severe structural and functional
defects in the anther, producing neither microsporangium nor pollen grains.
Therefore, we propose that the GIF family of Arabidopsis is a novel and essential
component required for the cell specification maintenance during reproductive
organ development and, ultimately, for the reproductive competence.
PMID- 24355748
TI - Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of
the piRNA pathway.
AB - To preserve genome integrity, an evolutionarily conserved small RNA-based
silencing mechanism involving PIWI proteins and PIWI-interacting RNAs (piRNAs)
represses potentially deleterious transposons in animals. Although there has been
extensive research into PIWI proteins in bilaterians, these proteins remain to be
examined in ancient phyla. Here, we investigated the PIWI proteins Hywi and Hyli
in the cnidarian Hydra, and found that both PIWI proteins are enriched in
multipotent stem cells, germline stem cells, and in the female germline. Hywi and
Hyli localize to the nuage, a perinuclear organelle that has been implicated in
piRNA-mediated transposon silencing, together with other conserved nuage and
piRNA pathway components. Our findings provide the first report of nuage protein
localization patterns in a non-bilaterian. Hydra PIWI proteins possess
symmetrical dimethylarginines: modified residues that are known to aid in PIWI
protein localization to the nuage and proper piRNA loading. piRNA profiling
suggests that transposons are the major targets of the piRNA pathway in Hydra.
Our data suggest that piRNA biogenesis through the ping-pong amplification cycle
occurs in Hydra and that Hywi and Hyli are likely to preferentially bind primary
and secondary piRNAs, respectively. Presumptive piRNA clusters are
unidirectionally transcribed and primarily give rise to piRNAs that are antisense
to transposons. These results indicate that various conserved features of PIWI
proteins, the piRNA pathway, and their associations with the nuage were likely
established before the evolution of bilaterians.
PMID- 24355749
TI - Deletion of MgcRacGAP in the male germ cells impairs spermatogenesis and causes
male sterility in the mouse.
AB - MgcRacGAP (RACGAP1) is a GTPase Activating Protein (GAP), highly produced in the
mouse embryonic brain and in the human and mouse post-natal testis. MgcRacGAP
negatively controls the activity of Rac and Cdc42, which are key molecular
switches acting on the microtubule and actin cytoskeleton and controlling various
cell processes such as proliferation, adhesion and motility. Previous studies
demonstrated that MgcRacGAP plays a critical role in the cytokinesis of somatic
cells; hence homozygous inactivation of the gene in the mouse and mutation in
Caenorhabditis elegans led to embryonic lethality due to the inability of
MgcRacGAP-null embryos to assemble the central spindle and to complete
cytokinesis. In the testis, the germ cells do not complete cytokinesis and remain
connected as a syncytium throughout the entire process of spermatogenesis.
Interestingly, MgcRacGAP was shown to locate to the intercellular bridges,
connecting these germ cells. In order to determine the function(s) of MgcRacGAP
in the male germline, we generated a conditional knock-out mouse using Stra8
promoter driven Cre recombinase to induce the specific deletion of MgcRacGAP in
the pre-meiotic germ cells. We found that the absence of MgcRacGAP induced a
germline depletion and male sterility. Consistent with the role of MgcRacGAP in
the establishment of the cytoplasm constriction during cytokinesis of the somatic
cells, we observed that MgcRacGAP deletion in the germ cells prevented the
formation of the intercellular bridges and induced a proliferation arrest. While
we assume that inherited homozygous loss of function mutations in MgcRacGAP would
be lethal in human, de novo mutations in the testis might account for some cases
of non-obstructive oligo- and/or azoo-spermia syndromes, whose genetic causes are
altogether still poorly defined.
PMID- 24355750
TI - Multiple sclerosis-associated retrovirus and related human endogenous retrovirus
W in patients with multiple sclerosis.
PMID- 24355751
TI - Sensory deprivation: visual experience alters the mental number line.
AB - Early studies on numeric cognition reported that numbers are spatially organised
according to a left-to-right small-to-large 'number line'. We investigated
whether this spatial-number organisation is dictated by visual experience. We
tested congenitally and late blind, and blindfolded sighted participants in a
random number generation task where in one block their heads were alternately
turned left or right before uttering the number. We found that the 'random'
number generation was biased according to the side where the head was turned to.
Consistent with the standard number line, participants with visual experience
generated smaller numbers for left turns, and larger numbers for right turns. In
contrast, participants without any visual experience showed the opposite pattern
of results. These results suggest a role for visual experience in the development
of spatial and numerical representations, which is supported by cultural
differences in number representation, and provide converging evidence for
visually driven organisation of the parietal cortex.
PMID- 24355752
TI - Investigation of decision-making under uncertainty in healthy subjects: a multi
centric fMRI study.
AB - Decision-making is an everyday routine that entails several subprocesses.
Decisions under uncertainty occur when either prior information is incomplete or
the outcomes of the decision are unclear. The aim of the present study was to
disentangle the neural correlates of information gathering as well as reaching a
decision and to explore effects of uncertainty acceptance or avoidance in a large
sample of healthy subjects. Sixty-four healthy volunteers performed a decision
making under uncertainty task in a multi-center approach while BOLD signal was
measured with fMRI. Subjects either had to indicate via button press from which
of two bottles red or blue balls were drawn (decision-making under uncertainty
condition), or they had to indicate whether 8 red balls had been presented
(baseline condition). During the information gathering phase (contrasted against
the counting phase) a widespread network was found encompassing (pre-)frontal,
inferior temporal and inferior parietal cortices. Reaching a decision was
correlated with activations in the medial frontal cortex as well as the posterior
cingulate and the precuneus. Effects of uncertainty acceptance were found within
a network comprising of the superior frontal cortex as well as the insula and
precuneus while uncertainty avoidance was correlated with activations in the
right middle frontal cortex. The results depict two distinct networks for
information gathering and the indication of having made a decision. While
information-gathering networks are modulated by uncertainty avoidance and -
acceptance, underlying networks of the decision itself are independent of these
factors.
PMID- 24355753
TI - Acute exposure to ethanol on gestational day 15 affects social motivation of
female offspring.
AB - Alterations in social behavior are a hallmark of many neurodevelopmental
disorders in humans. In rodents, social behavior is affected by prenatal insults.
The outcomes are dependent on the timing of the insult as well as the sex and age
of the animal tested. The limbic system is particularly important for social
behavior, and a peak of neurogenesis within this system occurs on gestational day
(G)15. Neurons appear particularly vulnerable to ethanol insult around the time
they become post-mitotic. We tested the hypothesis that acute exposure to ethanol
on G15 would result in significant social behavior deficits. Accordingly, Long
Evans pregnant females were injected with ethanol (2.9 g/kg) or an equivalent
volume of saline on G15. Offspring were assessed in a modified social interaction
test on postnatal day (P) 28, P42, or P75, i.e., during early adolescence, late
adolescence, or young adulthood. Prenatal ethanol exposure decreased social
investigation in P28 females and transformed social preference into social
avoidance in 75-day-old females. Contact behavior, play fighting, and locomotor
activity differed as a function of age, but were not significantly affected by
ethanol exposure. Males demonstrated significantly more contact behavior and play
fighting at P42 than at P28 or P70, whereas there were no age-related changes in
females. Adult females showed more locomotor activity than adult males. Overall,
prenatal ethanol exposure on G15 enhanced social anxiety in females, with these
effects seen in adulthood only.
PMID- 24355754
TI - Smoking behaviour trends among Portuguese physicians: are they role models? A
conference-based survey.
PMID- 24355755
TI - Comorbidities impacting on prognosis after lung transplant.
AB - The aim of this review is to give an overview of the clinical circumstances
presenting before lung transplant that may have negative repercussions on the
long and short-term prognosis of the transplant. Methods for screening and
diagnosis of common comorbidities with negative impact on the prognosis of the
transplant are proposed, both for pulmonary and extrapulmonary diseases, and
measures aimed at correcting these factors are discussed. Coordination and
information exchange between referral centers and transplant centers would allow
these comorbidities to be detected and corrected, with the aim of minimizing the
risks and improving the life expectancy of transplant receivers.
PMID- 24355756
TI - The evolving use of non-invasive mechanical ventilation in chronic obstructive
pulmonary disease.
PMID- 24355757
TI - A characterization of the ZFL cell line and primary hepatocytes as in vitro liver
cell models for the zebrafish (Danio rerio).
AB - The zebrafish (Danio rerio) is a widely used model species in biomedical
research. The ZFL cell line, established from zebrafish liver, and freshly
isolated primary hepatocytes from zebrafish have been used in several
toxicological studies. However, no previous report has compared and characterized
these two systems at the level of gene expression. The aim of this study was to
evaluate the ZFL cell line in comparison to primary hepatocytes as in vitro
models for studying effects of environmental contaminants in zebrafish liver.
Using quantitative real-time PCR, the basal level and transcriptional induction
potential of key genes involved in toxic responses in the ZFL cell line, primary
hepatocytes and whole liver from zebrafish were compared. The study showed that
the ZFL cells have lower levels of mRNA of most selected genes compared to
zebrafish liver. The induced gene transcription following exposure to ligand was
much lower in ZFL cells compared to zebrafish primary hepatocytes at the doses
tested. Importantly, oestrogen receptor and vitellogenin genes showed low basal
transcription and no induction response in the ZFL cell line. In conclusion, it
appears that primary hepatocytes are well suited for studying environmental
contaminants including xenoestrogens, but may show large sex-dependent
differences in gene transcription. The ZFL cell line shows potential in
toxicological studies involving the aryl hydrocarbon receptor pathway. However,
low potential for transcriptional induction of genes in general should be
expected, especially notable when studying estrogenic responses.
PMID- 24355758
TI - Tissue-specific gene silencing monitored in circulating RNA.
AB - Pharmacologic target gene modulation is the primary objective for RNA antagonist
strategies and gene therapy. Here we show that mRNAs encoding tissue-specific
gene transcripts can be detected in biological fluids and that RNAi-mediated
target gene silencing in the liver and brain results in quantitative reductions
in serum and cerebrospinal fluid mRNA levels, respectively. Further,
administration of an anti-miRNA oligonucleotide resulted in decreased levels of
the miRNA in circulation. Moreover, ectopic expression of an adenoviral transgene
in the liver was quantified based on measurement of serum mRNA levels. This
noninvasive method for monitoring tissue-specific RNA modulation could greatly
advance the clinical development of RNA-based therapeutics.
PMID- 24355759
TI - ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use
criteria for the detection and risk assessment of stable ischemic heart disease:
a report of the American College of Cardiology Foundation Appropriate Use
Criteria Task Force, American Heart Association, American Society of
Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society
of America, Heart Rhythm Society, Society for Cardiovascular Angiography and
Interventions, Society of Cardiovascular Computed Tomography, Society for
Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
AB - The American College of Cardiology Foundation along with key specialty and
subspecialty societies, conducted an appropriate use review of common clinical
presentations for stable ischemic heart disease (SIHD) to consider use of stress
testing and anatomic diagnostic procedures. This document reflects an updating of
the prior Appropriate Use Criteria (AUC) published for radionuclide imaging
(RNI), stress echocardiography (Echo), calcium scoring, coronary computed
tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and
invasive coronary angiography for SIHD. This is in keeping with the commitment to
revise and refine the AUC on a frequent basis. A major innovation in this
document is the rating of tests side by side for the same indication. The side-by
side rating removes any concerns about differences in indication or
interpretation stemming from prior use of separate documents for each test.
However, the ratings were explicitly not competitive rankings due to the limited
availability of comparative evidence, patient variability, and range of
capabilities available in any given local setting. The indications for this
review are limited to the detection and risk assessment of SIHD and were drawn
from common applications or anticipated uses, as well as from current clinical
practice guidelines. Eighty clinical scenarios were developed by a writing
committee and scored by a separate rating panel on a scale of 1 to 9, to
designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a
modified Delphi process following the recently updated AUC development
methodology. The use of some modalities of testing in the initial evaluation of
patients with symptoms representing ischemic equivalents, newly diagnosed heart
failure, arrhythmias, and syncope was generally found to be Appropriate or May Be
Appropriate, except in cases where low pre-test probability or low risk limited
the benefit of most testing except exercise electrocardiogram (ECG). Testing for
the evaluation of new or worsening symptoms following a prior test or procedure
was found to be Appropriate. In addition, testing was found to be Appropriate or
May Be Appropriate for patients within 90 days of an abnormal or uncertain prior
result. Pre-operative testing was rated Appropriate or May Be Appropriate only
for patients who had poor functional capacity and were undergoing vascular or
intermediate risk surgery with 1 or more clinical risk factors or an organ
transplant. The exercise ECG was suggested as an Appropriate test for cardiac
rehabilitation clearance or for exercise prescription purposes. Testing in
asymptomatic patients was generally found to be Rarely Appropriate, except for
calcium scoring and exercise testing in intermediate and high-risk individuals
and either stress or anatomic imaging in higher-risk individuals, which were all
rated as May Be Appropriate. All modalities of follow-up testing after a prior
test or percutaneous coronary intervention (PCI) within 2 years and within 5
years after coronary artery bypass graft (CABG) in the absence of new symptoms
were rated Rarely Appropriate. Pre-operative testing for patients with good
functional capacity, prior normal testing within 1 year, or prior to low-risk
surgery also were found to be Rarely Appropriate. Imaging for an exercise
prescription or prior to the initiation of cardiac rehabilitation was Rarely
Appropriate except for cardiac rehabilitation clearance for heart failure
patients.
PMID- 24355760
TI - [Anesthesiology treatment of an "open book" pelvic fracture due to an explosion].
PMID- 24355761
TI - TDP-43-mediated neurodegeneration: towards a loss-of-function hypothesis?
AB - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are
clinically distinct fatal neurodegenerative disorders. Increasing molecular
evidence indicates that both disorders are linked in a continuous spectrum (ALS
FTD spectrum). Neuronal cytoplasmic inclusions consisting of the nuclear TAR DNA
binding protein 43 (TDP-43) are found in the large majority of patients in the
ALS-FTD spectrum and dominant mutations in the TDP-43 gene cause ALS. A major
unresolved question is whether TDP-43-mediated neuronal loss is caused by toxic
gain of function of cytoplasmic aggregates, or by a loss of its normal function
in the nucleus. Here we argue that based on recent genetic studies in worms,
flies, fish, and rodents, loss of function of TDP-43, rather than toxic
aggregates, is the key factor in TDP-43-related proteinopathies.
PMID- 24355762
TI - How pregnancy at early age protects against breast cancer.
AB - Pregnancy at an early age has a strong protective effect against breast cancer in
humans and rodents. Postulated mechanisms underlying this phenomenon include
alterations in the relative dynamics of hormone and growth factor-initiated cell
fate-determining signaling pathways within the hierarchically organized mammary
gland epithelium. Recent studies in epithelial cell subpopulations isolated from
mouse and human mammary glands have shown that early pregnancy decreases the
proportion of hormone receptor-positive cells and causes pronounced changes in
gene expression as well as decreased proliferation in stem/progenitor cells. The
changes include downregulation of Wnt and transforming growth factor beta
(TGFbeta) signaling. These new findings highlight the importance of cell-cell
interactions within the mammary gland epithelium in modulating cancer risk and
provide potential targets for breast cancer prevention strategies.
PMID- 24355763
TI - The molecular path to in vitro shoot regeneration.
AB - Plant regeneration through de novo shoot organogenesis in tissue culture is a
critical step in most plant transformation and micropropagation procedures.
Establishing an efficient regeneration protocol is an empirical process and
requires optimization of multiple factors that influence the regeneration
capacity. Here, we review the molecular process of shoot induction in a two-step
regeneration protocol and focus on the role of auxins and cytokinins. First,
during incubation on an auxin-rich callus induction medium (CIM), organogenic
callus is produced that exhibits characteristics of a root meristem. Subsequent
incubation on a cytokinin-rich shoot induction medium (SIM) induces root to shoot
conversion. Through a detailed analysis of the different aspects of shoot
regeneration, we try to reveal hinge points and novel candidate genes that may be
targeted to increase shoot regeneration capacity in order to improve
transformation protocols.
PMID- 24355764
TI - Spotted fever group rickettsiae in ticks in Turkey.
AB - One hundred twenty-six ticks belonging to 12 tick species were collected from
humans, domestic and wild animals, and from the ground as unfed (questing ticks)
from distinct localities in Turkey in 2011. Ticks were individually tested by
polymerase chain reaction (PCR) for Rickettsia spp., amplifying citrate synthase
(gltA), and outer membrane protein (ompA) genes. Twenty-five ticks (19.8%) were
found to be infected with Rickettsia species. Five SFG rickettsiae were
identified, including 4 pathogens: Ri. aeschlimannii in Hyalomma marginatum, Hy.
aegyptium, Hyalomma sp. (nymph), and Rhipicephalus turanicus; Ri. africae in Hy.
excavatum, Hy. aegyptium, and Hyalomma sp. (nymph); Ri. slovaca and Ri. raoultii
in Dermacentor marginatus; and one species with unknown pathogenicity, Ri.
hoogstraalii, in Haemaphysalis parva. Rickettsia slovaca and Ri. hoogstraalii
were reported for the first time from Turkey. In addition, Ri. hoogstraalii and
Ri. africae were detected for the first time in Ha. parva and Hy. excavatum
ticks, respectively.
PMID- 24355765
TI - Fetal hemoglobin in sickle cell anemia.
PMID- 24355766
TI - Identification of four SLC19A2 mutations in four Chinese thiamine responsive
megaloblastic anemia patients without diabetes.
PMID- 24355767
TI - Efficacy of Curcumin in the healing of paracentesis in rats.
AB - OBJECTIVES: The present study was designed to investigate the possible beneficial
effect of Curcumin (CMN) in healing of paracentesis in terms of wound thickness,
sclerosis and closure by histological evaluation. To evaluate the efficacy of
CMN, paracentesis was performed experimentally in the rats; and the results were
presented histologically. METHODS: Sixteen, each 270-310g weighted, healthy
Sprague-Dawley female rats were included into the study. In both groups,
paracentesis was performed into the eardrum bilaterally. In Group 1
(Paracentesis+Saline Group), saline drop was applied; and in Group 2
(Paracentesis+Curcumin group), Curcumin drop treatment was applied. Paracentesis
area did not healed bilaterally in two rats (one in Group 1 and one in Group 2).
Therefore, these two rats were excluded from the study. Histological examination
performed in 14 rats and 28 temporal bones on the 15th day after the completion
of drop treatment and closure of the paracentesis-area and wound healing were
evaluated according to the histological examination criteria: Thickening of the
tympanic membrane (ThicTM); and sclerosis. RESULTS: Both tympanic membrane
thickening and sclerosis values of Paracentesis+Curcumin Group (Group 2) were
significantly lower than those of the Paracentesis+Saline Group's (median: 2.0)
(p=0.001). Histological examination by light microscopy showed that in
Paracentesis+Curcumin Group (Group 2), the structure of the tympanic membrane is
near to the normal and decreased sclerosis was observed in connective tissue.
Whereas in Paracentesis+Saline Group (Group 1), tympanic membrane thickening and
connective tissue sclerosis were observed. CONCLUSIONS: Curcumin improves wound
healing process in paracentesis of TM. By using Curcumin drops, the closured
paracentesis area was observed near to the normal eardrum; and thickness of the
TM and sclerosis were less than the control, showing the improved healing at 15th
day. The possible mechanisms may be anti-inflammatory effect, improving collagen
deposition, and increasing fibroblast and vascular density in wounds thereby
enhancing impaired wound healing.
PMID- 24355768
TI - The effects of antimicrobials and exposure to smoking on bacterial interference
in the upper respiratory tract of children.
AB - Interactions between micro-organisms that include antagonism (interference) and
synergism maintain balance between members of the normal endogenous flora, and
play a role in preventing colonization by potential pathogens. Bacteria with
interference capability of potential respiratory tract pathogens include alpha
hemolytic streptococci, non-hemolytic streptococci, Prevotella spp. and
Peptostreptococcus spp. The role of bacterial interference in the occurrence of
upper respiratory tract infections and its effect on their eradication is
discussed. The infections include otitis media, sinusitis and pharyngo
tonsillitis. Treatment with antimicrobial agents and direct and indirect exposure
to smoking, can affect the balance between the interfering organisms and
potential pathogens. Introduction into the indigenous microflora of low virulence
bacterial strains that are capable of interfering with colonization and infection
with virulent organisms has been used to prevent the failure of antimicrobials in
the treatment of pharyngo-tonsillitis and otitis media.
PMID- 24355769
TI - Conventional protein kinase C isoforms mediate phorbol ester-induced
lysophosphatidic acid LPA1 receptor phosphorylation.
AB - Using C9 cells stably expressing LPA1 receptors fused to the enhanced green
fluorescent protein, it was observed that activation of protein kinase C induced
a rapid and strong increase in the phosphorylation state of these receptors.
Overnight incubation with phorbol esters markedly decreased the amount of
conventional (alpha, betaI, betaII and gamma) and novel (delta) but not atypical
(zeta) immunodetected PKC isoforms, this treatment blocks the action of protein
kinase on receptor function and phosphorylation. Bis-indolylmaleimide I a
general, non-subtype selective protein kinase C inhibitor, and Go 6976, selective
for the isoforms alpha and beta, were also able to block LPA1 receptor
desensitization and phosphorylation; hispidin, isoform beta-selective blocker
partially avoided receptor desensitization. Expression of dominant-negative
protein kinase C alpha or beta II mutants and knocking down the expression of
these kinase isozymes markedly decreased phorbol ester-induced LPA1 receptor
phosphorylation without avoiding receptor desensitization. This effect was
blocked by bis-indolyl-maleimide and Go 6976, suggesting that these genetic
interventions were not completely effective. It was also observed that protein
kinase C alpha and beta II isozymes co-immunoprecipitate with LPA1 receptors and
that such an association was further increased by cell treatments with phorbol
esters or lysophosphatidic acid. Our data suggest that conventional protein
kinase C alpha and beta isozymes modulate LPA1 receptor phosphorylation state.
Receptor desensitization appears to be a more complex process that might involve
additional elements.
PMID- 24355770
TI - Does adoption of a regional sepsis protocol reduce mortality?
PMID- 24355771
TI - Sigmoid volvulus in pregnancy: early diagnosis and intervention are important.
AB - Bowel obstruction is rare in pregnancy, and delay in recognition can lead to
serious maternal and fetal complications. Most reported causes of bowel
obstruction in pregnancy (adhesions, intussusception, hernia, and carcinoma)
require surgical intervention. Sigmoid volvulus is an acute surgical cause that
can now be managed successfully without surgery. We report the case of 33-year
old lady who presented with a sigmoid volvulus that was successfully managed with
urgent endoscopic decompression.
PMID- 24355772
TI - Acute abdominal pain due to spontaneous rupture of the right gastric artery.
AB - Abdominal apoplexy was reported by Barber in 1909, and the occurrence rate of the
apoplexy is known to be quite rare, but the mortality is high if untreated. We
report an unusual case of abdominal apoplexy due to spontaneous rupture of
gastric artery. A male patient in his fifth decade with recently diagnosed liver
cirrhosis history arrived to the emergency department with severe abdominal pain,
which led to abdominal computer tomography indicating spontaneous rupture of
gastric artery. Celiac angiogram and embolization were conducted, and exploratory
laparotomy was followed. The outcome of the patient was poor, and he died on the
second day of admission. As in our case, the mortality can be high, so prompt
restoration of circulation volume and early diagnosis should be made in similar
cases.
PMID- 24355773
TI - The evaluation of four recent culture-based methods for the isolation and
enumeration of Vibrio vulnificus bacteria from oyster meat.
AB - The most common cause of seafood-borne death in the United States is the
bacterium Vibrio vulnificus which can be concentrated into high numbers in the
tissues of oysters or other shellfish. The ability to quickly, accurately, and
inexpensively isolate living strains of this organism from oyster tissues is
crucial for effective research on this pathogen. In this report, we evaluate four
methods for isolating and quantifying V. vulnificus from oyster tissues, the
solid media CPC+ (a refined version of cellobiose-polymyxin B-colistin medium),
CHROMagar Vibrio, VVX (Vibrio vulnificus X-gal), and a method termed "Triple
plating". Up to 1225 presumptive isolates were detected by each method, and 335
were subjected to molecular typing. The selectivity and sensitivity of each
method was examined and VVX was found to be the most accurate method, with each
of the other methods being recommended for task-specific uses. CHROMagar Vibrio
is recommended for ease of use and relative accuracy, CPC+ is best used to
differentiate between clinically associated and environmental strains.
PMID- 24355775
TI - Effective decoration of Pd nanoparticles on the surface of SnO2 nanowires for
enhancement of CO gas-sensing performance.
AB - Decoration of noble metal nanoparticles (NPs) on the surface of semiconducting
metal oxide nanowires (NWs) to enhance material characteristics,
functionalization, and sensing abilities has attracted increasing interests from
researchers worldwide. In this study, we introduce an effective method for the
decoration of Pd NPs on the surface of SnO2 NWs to enhance CO gas-sensing
performance. Single-crystal SnO2 NWs were fabricated by chemical vapor
deposition, whereas Pd NPs were decorated on the surface of SnO2 NWs by in situ
reduction of the Pd complex at room temperature without using any linker or
reduction agent excepting the copolymer P123. The materials were characterized by
advanced techniques, such as high-resolution transmission electron microscopy,
scanning transmission electron microscopy, and energy-dispersive X-ray
spectroscopy. The Pd NPs were effectively decorated on the surface of SnO2 NWs.
As an example, the CO sensing characteristics of SnO2 NWs decorated with Pd NPs
were investigated at different temperatures. Results revealed that the gas sensor
exhibited excellent sensing performance to CO at low concentration (1-25ppm) with
ultrafast response-recovery time (in seconds), high responsivity, good stability,
and reproducibility.
PMID- 24355774
TI - The rod-driven a-wave of the dark-adapted mammalian electroretinogram.
AB - The a-wave of the electroretinogram (ERG) reflects the response of photoreceptors
to light, but what determines the exact waveform of the recorded voltage is not
entirely understood. We have now simulated the trans-retinal voltage generated by
the photocurrent of dark-adapted mammalian rods, using an electrical model based
on the in vitro measurements of Hagins et al. (1970) and Arden (1976) in rat
retinas. Our simulations indicate that in addition to the voltage produced by
extracellular flow of photocurrent from rod outer to inner segments, a
substantial fraction of the recorded a-wave is generated by current that flows in
the outer nuclear layer (ONL) to hyperpolarize the rod axon and synaptic
terminal. This current includes a transient capacitive component that contributes
an initial negative "nose" to the trans-retinal voltage when the stimulus is
strong. Recordings in various species of the a-wave, including the peak and
initial recovery towards the baseline, are consistent with simulations showing an
initial transient primarily related to capacitive currents in the ONL. Existence
of these capacitive currents can explain why there is always a substantial
residual transient a-wave when post-receptoral responses are pharmacologically
inactivated in rodents and nonhuman primates, or severely genetically compromised
in humans (e.g. complete congenital stationary night blindness) and nob mice. Our
simulations and analysis of ERGs indicate that the timing of the leading edge and
peak of dark-adapted a-waves evoked by strong stimuli could be used in a simple
way to estimate rod sensitivity.
PMID- 24355776
TI - Automated evaluation of pharmaceutically active ionic liquids' (eco)toxicity
through the inhibition of human carboxylesterase and Vibrio fischeri.
AB - The toxicity of 16 pharmaceutical active ionic liquids (IL-APIs) was evaluated by
automated approaches based on sequential injection analysis (SIA). The
implemented bioassays were centered on the inhibition of human carboxylesterase 2
and Vibrio fischeri, in the presence of the tested compounds. The inhibitory
effects were quantified by calculating the inhibitor concentration required to
cause 50% of inhibition (EC50). The EC50 values demonstrated that the
cetylpyridinium group was one of the most toxic cations and that the imidazolium
group was the less toxic. The obtained results provide important information
about the safety of the studied IL-APIs and their possible use as pharmaceutical
drugs. The developed automated SIA methodologies are robust screening bioassays,
and can be used as a generic tools to identify the (eco)toxicity of the
structural elements of ILs, contributing to a sustainable development of drugs.
PMID- 24355777
TI - Polyandry.
PMID- 24355778
TI - Physarum.
PMID- 24355779
TI - Ants use a predictive mechanism to compensate for passive displacements by wind.
PMID- 24355780
TI - Parental misperception of youngest child size.
PMID- 24355781
TI - Robust orienting to protofacial stimuli in autism.
PMID- 24355782
TI - Sensory cell fates: four defaults for the price of one.
AB - The specification of different subtypes of olfactory sensilla, which harbor the
olfactory receptor neurons (ORNs) in the Drosophila antennae, is poorly
understood. Loss of the transcription factor Rotund (Rn) leads to a simultaneous
mis-specification of several ORN classes, transforming them into different
'default' cell fates.
PMID- 24355783
TI - Olfactory neuroscience: normalization is the norm.
AB - A recent study shows that neural circuits from vertebrates and invertebrates use
common strategies to stabilize odor representations across a wide range of
concentrations.
PMID- 24355784
TI - Evolution: unveiling early alveolates.
AB - The isolation and characterisation of a novel protist lineage enables the
reconstruction of early evolutionary events that gave rise to ciliates, malaria
parasites, and coral symbionts. These events include dramatic changes in
mitochondrial genome content and organisation.
PMID- 24355785
TI - Early vision: where (some of) the magic happens.
AB - A recent study provides new insights into how the very different response
characteristics of the main visual pathways from the eye to the brain may
directly result from the presence or absence of a 'spike trigger-zone' in retinal
bipolar cells.
PMID- 24355786
TI - Conservation: forest fragments, facts, and fallacies.
AB - Most of the world's remaining habitats are split into small fragments that lose
species quickly. Knowledge of this fact can guide practical actions to prevent
extinctions.
PMID- 24355787
TI - Development: getting into the groove, or evolving off the rails?
AB - Canalization, the robust buffering against fluctuations, is often regarded as an
essential feature of development. A new study identifies a genetic circuit
dedicated to canalization in Drosophila melanogaster and shows striking
variability in its use in different fly species.
PMID- 24355788
TI - Evolution: a new cat species emerges.
AB - The complex ongoing process of species development is highlighted by the
description of a new felid species, Leopardus guttulus, from Brazil. Broad
molecular genetic assessments affirm reproductive isolation and separation in
nature, the hallmark of species recognition.
PMID- 24355789
TI - Meiosis: cohesin's hidden role in the checkpoint revealed.
AB - The spindle assembly checkpoint prevents aneuploidy by ensuring that chromosomes
are properly distributed during cell division. A new study shows that the
integrity of the checkpoint response depends on centromeric cohesin in mammalian
oocytes.
PMID- 24355790
TI - Neuroethology: lemon-fresh scent makes flies lay eggs.
AB - A new study reveals how Drosophila uses their sense of smell to decide on where
to lay their eggs. These results have exciting implications for the evolution of
fruit preference and parasitoid avoidance in fruit flies.
PMID- 24355791
TI - Visual attention: a rhythmic process?
AB - Vision involves constant exploration of the environment by eye movements. Recent
evidence suggests that a rhythmic form of exploration also occurs under covert
attention, in the absence of eye movements. Sustained attention naturally
fluctuates, with a periodicity in the theta (4-8 Hz) frequency range.
PMID- 24355793
TI - Influence of dietary fat on intestinal microbes, inflammation, barrier function
and metabolic outcomes.
AB - Recent studies using germ-free, gnotobiotic microbial
transplantation/conventionalization or antibiotic treatment in rodent models have
highlighted the critical role of intestinal microbes on gut health and metabolic
functions of the host. Genetic and environmental factors influence the abundance
and type of mutualistic vs. pathogenic bacteria, each of which has preferred
substrates for growth and unique products of fermentation. Whereas some
fermentation products or metabolites promote gut function and health, others
impair gut function, leading to compromised nutrient digestion and barrier
function that adversely impact the host. Such products may also influence food
intake, energy harvest and expenditure, and insulin action, thereby influencing
adiposity and related metabolic outcomes. Diet composition influences gut
microbiota and subsequent fermentation products that impact the host, as
demonstrated by prebiotic studies using oligosaccharides or other types of
indigestible fiber. Recent studies also show that dietary lipids affect specific
populations of gut microbes and their metabolic end products. This review will
focus on studies examining the influence of dietary fat amount and type on the
gut microbiome, intestinal health and positive and negative metabolic
consequences. The protective role of omega-3-rich fatty acids on intestinal
inflammation will also be examined.
PMID- 24355792
TI - Nuclear mechanics and mechanotransduction in health and disease.
AB - The nucleus is the defining feature of eukaryotic cells and often represents the
largest organelle. Over the past decade, it has become apparent that the nucleus
is tightly integrated into the structural network of the cell through so-called
LINC (linker of the nucleoskeleton and cytoskeleton) complexes, which enable
transmission of forces between the nucleus and cytoskeleton. This physical
connection between the nucleus and the cytoskeleton is essential for a broad
range of cellular functions, including intracellular nuclear movement and
positioning, cytoskeletal organization, cell polarization, and cell migration.
Recent reports further indicate that forces transmitted from the extracellular
matrix to the nucleus via the cytoskeleton may also directly contribute to the
cell's ability to probe its mechanical environment by triggering force-induced
changes in nuclear structures. In addition, it is now emerging that the physical
properties of the nucleus play a crucial role during cell migration in three
dimensional (3D) environments, where cells often have to transit through narrow
constrictions that are smaller than the nuclear diameter, e.g., during
development, wound healing, or cancer metastasis. In this review, we provide a
brief overview of how LINC complex proteins and lamins facilitate nucleo
cytoskeletal coupling, highlight recent findings regarding the role of the
nucleus in cellular mechanotransduction and cell motility in 3D environments, and
discuss how mutations and/or changes in the expression of these nuclear envelope
proteins can result in a broad range of human diseases, including muscular
dystrophy, dilated cardiomyopathy, and premature aging.
PMID- 24355794
TI - A study on circadian rhythm disorder of rat lung tissue caused by mechanical
ventilation induced lung injury.
AB - Ventilator-induced lung injury (VILI), the most serious complication of
mechanical ventilation therapy, is an excessive inflammatory response in lung
tissue characterized by infiltration of inflammatory cells and overproduction of
inflammatory mediators. The pathogenesis of VILI is very complex. It is becoming
increasingly evident that disruption of circadian rhythm affects the immune
response. Whether the pathogenesis of VILI is associated with circadian rhythm
disruption has not been reported. In this study, we establish VILI model in SD
rat by performing an endotracheal intubation and placing the rat on a mechanical
ventilator (tidal volume of 40 ml/kg or 10 ml/kg without positive end-expiratory
pressure). To examine the effect of VILI on clock gene expression, real-time
quantitative PCR was performed to measure bmal1, clock, per2 and Rev-erbalpha
mRNA expression. We found that Rev-erbalpha mRNA was significantly decreased in
high tide volume mechanical ventilation group compared with spontaneous group,
the same as REV-ERBalpha protein product which was tested by Western blot
approach. Stimulation of REV-ERBalpha activity by SR9009 greatly diminished VILI
induced lung edema, inflammatory cell infiltration and the production of the pro
inflammatory cytokine TNF-alpha. Collectively, our findings are the first to show
that REV-ERBalpha plays an important role in VILI and inflammation, and circadian
rhythm disorder in inflammation response may be a novel pathogenesis of VILI.
PMID- 24355795
TI - Inflammatory cytokines in Paget's disease of bone.
AB - This study was undertaken to evaluate the expression of inflammatory cytokines in
patients with Paget's disease of bone (PDB). Serum levels of tumoral necrosis
factor-alpha, interleukin 1beta, interleukin-6 and interleukin-17 were measured
in 51 patients with PDB and in 24 controls with primary osteoarthritis. Compared
to controls, patients with Paget's disease of bone presented higher levels of
interleukin 6 and reduced interleukin 17, but levels of tumoral necrosis factor
alpha and interleukin 1 beta did not differ significantly. We found no
significant differences when patients were compared according to disease activity
or current treatment. There were no correlations between cytokine levels and bone
specific alkaline phosphatase or extension of Paget's disease of bone on bone
scintigraphs. In conclusion, patients with PDB present significant differences on
levels of certain cytokines in comparison to primary osteoarthritis patients, but
these alterations did not appear to have a clear correlation with parameters of
disease activity or severity.
PMID- 24355796
TI - Aspartame-induced apoptosis in PC12 cells.
AB - Aspartame is an artificial sweetner added to many low-calorie foods. The safety
of aspartame remains controversial even though there are many studies on its
risks. In this study, to understand the physiological effects of trace amounts of
artificial sweetners on cells, the effects of aspartame on apoptosis were
investigated using a PC12 cell system. In addition, the mechanism of apoptosis
induced by aspartame in PC12 cells and effects on apoptotic factors such as
cytochrome c, apoptosis-inducing factor, and caspase family proteins were studied
by Western blotting and RT-PCR. Aspartame-induced apoptosis in PC12 cells in a
dose-dependent manner. In addition, aspartame exposure increased the expressions
of caspases 8 and 9, and cytochrome c. These results indicate that aspartame
induces apoptosis mainly via mitochondrial pathway involved in apoptosis due to
oxigen toxicity.
PMID- 24355797
TI - Oxidation of siloxanes during biogas combustion and nanotoxicity of Si-based
particles released to the atmosphere.
AB - Siloxanes have been detected in the biogas produced at municipal solid waste
landfills and wastewater treatment plants. When oxidized, siloxanes are converted
to silicon oxides. The objectives of this study were to evaluate the
transformation of siloxanes and potential nanotoxicity of Si-based particles
released to the atmosphere from the gas engines which utilize biogas. Data
available from nanotoxicity studies were used to assess the potential health
risks associated with the inhalation exposure to Si-based nanoparticles. Silicon
dioxide formed from siloxanes can range from 5 nm to about 100 nm in diameter
depending on the combustion temperature and particle clustering characteristics.
In general, silicon dioxide particles formed during from combustion process are
typically 40-70 nm in diameter and can be described as fibrous dusts and as
carcinogenic, mutagenic, astmagenic or reproductive toxic (CMAR) nanoparticles.
Nanoparticles deposit in the upper respiratory system, conducting airways, and
the alveoli. Size ranges between 5 and 50 nm show effective deposition in the
alveoli where toxic effects are higher. In this study the quantities for the SiO2
formed and release during combustion of biogas were estimated based on biogas
utilization characteristics (gas compositions, temperature). The exposure to Si
based particles and potential effects in humans were analyzed in relation to
their particle size, release rates and availability in the atmosphere. The
analyses showed that about 54.5 and 73 kg/yr of SiO2 can be released during
combustion of biogas containing D4 and D5 at 14.1 mg/m(3) (1 ppm) and 15.1
mg/m(3) (1ppm), respectively, per MW energy yield.
PMID- 24355799
TI - Electronic properties of site-controlled (111)-oriented zinc-blende InGaAs/GaAs
quantum dots calculated using a symmetry-adapted k.p Hamiltonian.
AB - In this work, we present and evaluate a (111)-rotated eight-band k ?p Hamiltonian
for the zinc-blende crystal lattice to investigate the electronic properties of
site-controlled InGaAs/GaAs quantum dots grown along the [111] direction. We
derive the rotated Hamiltonian including strain and piezoelectric potentials. In
combination with our previously formulated (111)-oriented continuum elasticity
model, we employ this approach to investigate the electronic properties of a
realistic site-controlled (111)-grown InGaAs quantum dot. We combine these
studies with an evaluation of single-band effective mass and eight-band k ?p
models, to investigate the capabilities of these models for the description of
electronic properties of (111)-grown zinc-blende quantum dots. Moreover, the
influence of second-order piezoelectric contributions on the polarization
potential in such systems is studied. The description of the electronic structure
of nanostructures grown on (111)-oriented surfaces can now be achieved with
significantly reduced computational costs in comparison to calculations performed
using the conventional (001)-oriented models.
PMID- 24355798
TI - Oral supplementation with troxerutin (trihydroxyethylrutin), modulates lipid
peroxidation and antioxidant status in 1,2-dimethylhydrazine-induced rat colon
carcinogenesis.
AB - The present study was aimed to investigate the chemopreventive potential of
troxerutin on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by
evaluating the antioxidant and lipid peroxidation (LPO) status. Rats were
randomly divided into six groups. Group I rats served as control. Group II rats
received troxerutin (50 mg/kgb.w., p.o.) for 16 weeks. Groups III-VI rats
received subcutaneous injections of DMH (20 mg/kgb.w., s.c.) once a week, for the
first 4 weeks. In addition to DMH, groups IV-VI rats received troxerutin at the
doses of 12.5, 25 and 50 mg/kgb.w., respectively. In DMH treated rats, our
results showed decreased activities of antioxidants and increased levels of LPO
in the liver. Moreover, LPO and antioxidants in the colon were found to be
significantly diminished in DMH the treated rats. Furthermore, enhanced activity
of colonic vitamin C and vitamin E levels were observed in DMH alone treated rats
(group III), which was significantly reversed on troxerutin supplementation.
Troxerutin at the dose of 25 mg/kgb.w. had shown profound beneficial effects by
exhibiting near normal biochemical profile and well-preserved colon histology as
compared to the other two tested doses (12.5 and 50 mg/kgb.w.). These findings
suggest that troxerutin could serve as a novel agent for colon cancer
chemoprevention.
PMID- 24355800
TI - Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft
vasculopathy.
AB - OBJECTIVES: This study sought to evaluate the diagnostic performance of
multiparametric cardiovascular magnetic resonance (CMR) for detecting cardiac
allograft vasculopathy (CAV) using contemporary invasive epicardial artery and
microvascular assessment techniques as reference standards, and to compare the
performance of CMR with that of angiography. BACKGROUND: CAV continues to limit
the long-term survival of heart transplant recipients. Coronary angiography has a
Class I recommendation for CAV surveillance and annual or biannual surveillance
angiography is performed routinely in most centers. METHODS: All transplant
recipients referred for surveillance angiography at a single UK center over a 2
year period were prospectively screened for study eligibility. Patients
prospectively underwent coronary angiography followed by coronary intravascular
ultrasound, fractional flow reserve, and index of microcirculatory resistance.
Within 1 month, patients underwent multiparametric CMR, including assessment of
regional and global ventricular function, absolute myocardial blood flow
quantification, and myocardial tissue characterization. In addition, 10 healthy
volunteers underwent CMR. RESULTS: Forty-eight patients were recruited, median
7.1 years (interquartile range: 4.6 to 10.3 years) since transplantation. The CMR
myocardial perfusion reserve was the only independent predictor of both
epicardial (beta = -0.57, p < 0.001) and microvascular disease (beta = -0.60, p <
0.001) on stepwise multivariable regression. The CMR myocardial perfusion reserve
significantly outperformed angiography for detecting moderate CAV (area under the
curve, 0.89 [95% confidence interval (CI): 0.79 to 1.00] vs. 0.59 [95% CI: 0.42
to 0.77], p = 0.01) and severe CAV (area under the curve, 0.88 [95% CI: 0.78 to
0.98] vs. 0.67 [95% CI: 0.52 to 0.82], p = 0.05). CONCLUSIONS: CAV, including
epicardial and microvascular components, can be detected more accurately using
noninvasive CMR-based absolute myocardial blood flow assessment than with
invasive coronary angiography, the current clinical surveillance technique.
PMID- 24355801
TI - Surgical approach for patients with unusually located hydatid cyst.
AB - INTRODUCTION: Hydatid cyst is a parasitic disease caused by Echinococcus
granulosus whose people is the intermediate host. Although this parasite can
settle in any part of the human body, it is frequently seen in liver and lungs.
The rate of unusual located hydatid cyst outside of liver and lungs is 13,9%. In
this study, we aimed presenting unusual located hydatic cysts regarding 51
patients. MATERIAL AND METHOD: In this retrospective study, the files of the
patients operated in our department between 2005 and 2012 with the diagnosis of
hydatid cyst, characterized be an additional location besides liver and lung
involvement and located outside of liver and lung were controlled. FINDINGS: We
had a total of 51 patients between the ages of 6-79 (average age 35,34), 20 of
them were men (39%) and the others were women (61%) (men/women = 1.56). The cysts
outside of liver and lung were frequently seen in spleen (24/51), ovarium (9/51),
intraabdominal (8/51), brain (8/51), kidney (6/51), psoas muscle (1/51), bladder
(1/51), cervical lymph node (1/51), the heart(1/51) respectively. The most
frequent symptom in our patients was stomachache. Besides, symptoms of cough,
fever, respiratory disorder were present; only one patient suffered from
hemophtysis. While 32 patient out of 51 were treated by laparotomy, 8 patients
were operated with laparotomy and thoracotomy in the same session; the patient
with 2 ovarian cysts was submitted to cystectomy through laparoscopic surgery. As
a patient had a cyst both in brain and liver, he was submutted to laparotomy and
craniotomy. 46 cysts in 9 patients with lung involvement were treated with lung
resections: 7 wedges resection and 2 segmentectomies. The other lung cysts of the
analysed patients were treated by cystectomy and capitonnage. Bile leakage was
detected in a total of 7 patients: 3 of them were treated with T tube drainage
and the others were endoscopically healed by means of ERCP. CONCLUSION: The
incidence of hydatid cyst, which is an important health problem in endemic areas,
can be reduced by means of simple preventive measures. Its basic treatment is
surgery. Main objective of the surgery should be parenchyma sparing while taking
off completely the cysts. Although the disease is frequently seen in liver and
lung, other organ involvements should be considered. Thus, it does not matter
where hydatid cyst is seen, abdomen and thorax should be attentively controlled
by the simplest imaging method also outside of clinical symptoms. Abdomen and
thorax imaging should be carried out at least once in the two following years to
have an early detection of an eventual recurrence.
PMID- 24355802
TI - Nursing students' assessment of the learning environment in different clinical
settings.
AB - INTRODUCTION: Nursing students perform their clinical practice in different types
of clinical settings. The clinical learning environment is important for students
to be able to achieve desired learning outcomes. Knowledge is lacking about the
learning environment in different clinical settings. AIM: The aim was to compare
the learning environment in different clinical settings from the perspective of
the nursing students. DESIGN: A cross-sectional study with comparative design was
conducted. METHOD: Data was collected from 185 nursing students at three
universities by means of a questionnaire involving the Clinical Learning
Environment, Supervision and Nurse Teacher (CLES + T) evaluation scale. An open
ended question was added in order to ascertain reasons for dissatisfaction with
the clinical placement. RESULTS: The nursing students' satisfaction with the
placement did not differ between clinical settings. However, those with clinical
placement in hospital departments agreed more strongly that sufficient meaningful
learning situations occurred and that learning situations were multi-dimensional.
Some students reported that the character of the clinical setting made it
difficult to achieve the learning objectives. CONCLUSION: In the planning of the
clinical placement, attention must be paid to whether the setting offers the
student a meaningful learning situation where the appropriate learning outcome
may be achieved.
PMID- 24355803
TI - Caring For Kids Where They Live: interprofessional collaboration in teaching and
learning in school settings.
AB - Across North America, educators are challenged with finding learning
opportunities for students in the health professions. Faculty members with a
pediatric specialization in nursing recognized that schools were an ideal setting
to provide children with care from the health continuum including health
promotion, assessment and treatment, and chronic disease management. The faculty
of nursing at a Western Canadian University established a unique educational
approach by creating an interprofessional pediatric clinical learning experience
titled, Caring For Kids Where They Live. This practicum brings together students
in the health professions (nurses, dentists, and kinesiologists) and students and
their families from three urban schools; one elementary school and two high
schools. The primary goals of this partnership were to create an
interprofessional clinical learning experience and to promote health and wellness
of children and youth. This initiative far exceeded the initial goals. This
descriptive article with the use of reflective elements from student journals,
identifies learning that occurred in an environment whereby students from the
health professions had the opportunity to meet and interact, to collaborate, and
to gain experience in caring for children and youth.
PMID- 24355804
TI - Constructing the foundations for compassionate care: how service-learning affects
nursing students' attitudes towards the poor.
AB - When nurses possess negative attitudes toward people with low socio-economic
status it can negatively influence patient care. This study examines whether
providing care in a service-learning environment positively affects nursing
students' world views and empathy toward the poor. Using a pre-post design, the
Attitudes about Poverty and Poor People Scale and the Just World Scale were
administered to both a control group and nursing students engaged in a clinical
rotation at a low-income housing facility or homeless shelter in spring and fall
2010. Findings show the service learning treatment modestly enhanced empathy and
students' views on justice, while not improving superficial perceptions of the
poor.
PMID- 24355805
TI - Synthetic fusion-protein containing domains of Bt Cry1Ac and Allium sativum
lectin (ASAL) conferred enhanced insecticidal activity against major lepidopteran
pests.
AB - Different transgenic crop plants, developed with delta-endotoxins of Bacillus
thuringiensis (Bt) and mannose-specific plant lectins, exhibited significant
protection against chewing and sucking insects. In the present study, a synthetic
gene (cry-asal) encoding the fusion-protein having 488 amino acids, comprising DI
and DII domains from Bt Cry1Ac and Allium sativum agglutinin (ASAL), was cloned
and expressed in Escherichia coli. Ligand blot analysis disclosed that the fusion
protein could bind to more number of receptors of brush border membrane vesicle
(BBMV) proteins of Helicoverpa armigera. Artificial diet bioassays revealed that
0.025 MUg/g and 0.50 MUg/g of fusion-protein were sufficient to cause 100%
mortality in Pectinophora gossypiella and H. armigera insects, respectively. As
compared to Cry1Ac, the fusion-protein showed enhanced (8-fold and 30-fold)
insecticidal activity against two major lepidopteran pests. Binding of fusion
protein to the additional receptors in the midgut cells of insects is
attributable to its enhanced entomotoxic effect. The synthetic gene, first of its
kind, appears promising and might serve as a potential candidate for engineering
crop plants against major insect pests.
PMID- 24355806
TI - Neural differentiation of mouse embryonic and mesenchymal stem cells in a simple
medium containing synthetic serum replacement.
AB - Neural differentiation of embryonic and adult stem cells has been reported
previously. Several studies have used different proportions of serum or a
cocktail of growth and differentiation factors for this purpose. In the present
study, we examined neural differentiation of mouse embryonic stem (ES) cells in
KoSR-containing media. We also investigated neural differentiation of mouse
adipose tissue-derived stem cells (ADSCs) in a medium containing KoSR, a
synthetic serum replacement, and compared it with neural differentiation in low
serum condition. Meanwhile, effect of beta-ME on neural differentiation was
investigated in both conditions. As revealed by RT-PCR and immunocytochemistry
analyses, KoSR-containing medium induced neural differentiation of mouse ES
cells. Moreover, under the culture conditions we tested, ADSCs were
differentiated to neuron-like cells and expressed some neuronal markers. Low
concentration of beta-ME improved neuron-like differentiation of the ADSCs in the
4% FBS-supplemented medium, while addition of beta-ME in KoSR condition decreased
neural differentiation. KoSR-containing medium without any additional factor
improved generation of neuron-like cells, upregulated the expression of mature
neuronal markers and led to the formation of cytoplasmic processes. In summary,
our findings are indicating that mouse embryonic and mesenchymal stem cells are
capable of neural development in KoSR-containing media.
PMID- 24355807
TI - Next generation 1536-well oligonucleotide synthesizer with on-the-fly dispense.
AB - Here we report the development of our Next Generation Automated Multiplexed
Oligonucleotide Synthesizer (NG-1536-AMOS), capable of producing 1536 samples in
a single run using a multi-well filtered titer plate. With the potential to
synthesize up to 3456 samples per plate, we converted the BioRAPTR Flying Reagent
Dispenser into an open-well system where spent reagents are drained to waste
under vacuum. During synthesis, reagents are delivered on-the-fly to each micro
titer well at volumes <=5 MUl with plate speeds up to 150 mm/s. Using gas-phase
cleavage and deprotection, a full plate of 1536 60 mers may be processed with
same-day turnaround with an average yield per well at 3.5 nmol. Final product at
only $0.00277/base is eluted into a low-volume collection plate for immediate use
in downstream application (e.g. Biomek FX for versatile sample handling). Also,
crude oligonucleotide quality is comparable to that of commercial synthesis
instrumentation, with an error rate on the NG-1536-AMOS platform of 1.53/717
bases. Furthermore, mass spectral analysis on strands synthesized up to 80 bases
showed high purity with an average coupling efficiency of 99.5%.
PMID- 24355808
TI - Staphylococcal enterotoxin C2 promotes osteogenesis and suppresses
osteoclastogenesis of human mesenchymal stem cells.
AB - As a super-antigen, staphylococcal enterotoxin C2 (SEC2) stimulates the release
of massive inflammatory cytokines such as interferon-gamma (IFN-gamma),
interleukin-1 (IL-1) and interleukin-2 (IL-2) which are documented to implicate
osteoblast differentiation. In the present study, SEC2 was found to significantly
improve the osteoblast differentiation by up-regulating BMP2 and Runx2/Cbfa1
expression. Interferon (IFN)-inducible gene IFI16, a co-activator of Runx2/Cbfa1,
was also activated by SEC2 in the osteoblast differentiation. In addition,
exogenous introduction of SEC2 stimulated OPG expression and suppressed RANKL,
suggesting suppression of osteoclastogenesis in hMSCs. Therefore, our results
displayed that SEC2 plays an important role in the commitment of MSC to the
osteoblast and it might be a potential new therapeutic candidate for bone
regeneration.
PMID- 24355809
TI - BH3-mimetic drugs prevent tumour onset in an orthotopic mouse model of
hepatoblastoma.
AB - Drug resistance and metastasis remain major challenges in the treatment of high
risk hepatoblastoma (HB) and require the development of alternative therapeutic
strategies. Modulation of apoptosis in HB cells enhances the sensitivity of these
cells towards various drugs and has been discussed to enforce treatment. We
investigated the impact of apoptosis sensitisers, BH3-mimetics, on the
interaction between the host and HB to reduce tumour growth and dissemination
while enhancing immunity. BH3-mimetics, such as obatoclax and ABT-737, enhanced
the apoptosis-inducing effect of TRAIL and TNF-alpha resistant HB cells (HepT1
and HUH6). Tumour cell migration was inhibited by ABT-737 and more markedly by
obatoclax. In an orthotopic model of HB, tumour uptake was reduced when the cells
were pretreated with low concentrations of obatoclax. Only 1 of 7 mice developed
HB in the liver, compared with an incidence of 0.8 in the control group. In
summary, our study showed that apoptosis sensitisers had broader effects on HB
cells than expected including migration and susceptibility to cytokines in
addition to the known effects on drug sensitization. Sensitising HB to apoptosis
may also allow resistant HB to be targeted by immune cells and prevent tumour
cell dissemination.
PMID- 24355810
TI - Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the
original tumor growth behavior and are suitable for preclinical drug and
radiation sensitivity screening.
AB - Identification of new drugs and predicting drug response are major challenges in
oncology, especially for brain tumors, because total surgical resection is
difficult and radiation therapy or chemotherapy is often ineffective. With the
aim of developing a culture system close to in vivo conditions for testing new
drugs, we characterized an ex vivo three-dimensional culture system based on a
hyaluronic acid-rich hydrogel and compared it with classical two-dimensional
culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of
human glioblastomas were subjected to radiation therapy and chemotherapy drugs.
It appears that 3D hydrogel preserves the original cancer growth behavior and
enables assessment of the sensitivity of malignant gliomas to radiation and drugs
with regard to inter-tumoral heterogeneity of therapeutic response. It could be
used for preclinical assessment of new therapies.
PMID- 24355811
TI - Climate for innovation, 12-step orientation, and tobacco cessation treatment.
AB - This study examined the relationship between (1) three indicators of climate for
innovation (clinician skills, absence of program obstacles, policy-related
incentives) and adoption extensiveness of both behavioral treatments for tobacco
cessation (TC) and system-level support for TC in substance use disorder
treatment programs, (2) a program's 12-step treatment orientation and adoption
extensiveness, and (3) whether 12-step treatment orientation moderates the
relationship between climate for innovation and adoption extensiveness. Data were
obtained from a random sample of 1006 program administrators. Hierarchical
regression results showed that both absence of program obstacles and policy
related incentives are positively related to adoption extensiveness. Twelve-step
treatment orientation is neither related to adoption extensiveness nor a
moderator of the relationship between climate for innovation and adoption
extensiveness. Although the adoption of both behavioral treatments for TC and
system-level support for TC is not extensive, we conclude that a 12-step
treatment orientation neither hampers nor promotes adoption extensiveness.
PMID- 24355814
TI - The effect of a spot-on formulation containing polyunsaturated fatty acids and
essential oils on dogs with atopic dermatitis.
AB - Recent studies have shown that immunological aberrations and epidermal barrier
defects could be important in the pathogenesis of canine atopic dermatitis (CAD)
and that oral polyunsaturated fatty acids (PUFAs) might influence the epidermal
barrier. The aim of this study was to evaluate the effects of a spot-on
formulation containing PUFAs and essential oils on pruritus and lesions caused by
CAD. Forty-eight privately owned dogs of different breeds, ages and genders
diagnosed with atopic dermatitis were included in a randomized, double-blinded,
placebo-controlled, multicentre clinical trial. Dogs were treated with a spot-on
formulation containing PUFAs and essential oils or placebo on the dorsal neck
once weekly for 8weeks. Before and after the study, CAD extent and severity index
03 (CADESI-03) and pruritus scores were determined by veterinarians and owners,
respectively. There was significantly more improvement in CADESI-03 and pruritus
scores in the treatment group than in the placebo group (P=0.011 and P=0.036,
respectively). Additionally, more dogs improved by at least 50% in CADESI-03 and
pruritus scores in the treatment group than in the placebo group (P=0.008 and
P=0.070, respectively). No adverse reactions were observed. The topical
preparation containing PUFAs and essential oils was a safe treatment and
beneficial in ameliorating the clinical signs of CAD.
PMID- 24355812
TI - alpha1-antitrypsin deficiency and the hepatocytes - an elegans solution to drug
discovery.
AB - Hepatocytes are metabolically active cells of the liver that play an important
role in the biosynthesis of proteins including alpha1-antitrypsin. Mutations in
the alpha1-antitrypsin gene can lead to protein misfolding,
polymerization/aggregation and retention of protein within the endoplasmic
reticulum of hepatocytes. The intracellular accumulation of alpha1-antitrypsin
aggregates can lead to liver disease and increased likelihood of developing
hepatocellular carcinomas. Of note, only ~10% of individuals with alpha1
antitrypsin-deficiency develop severe liver disease suggesting that there are
other genetic and/or environmental factors that determine disease outcome. The
nematode, Caenorhabditis elegans, is a powerful genetic model organism to study
molecular aspects of human disease. In this review, we discuss the functional
similarities between the intestinal cells of C. elegans and human hepatocytes and
how a C. elegans model of alpha1-antitrypsin-deficiency can be used as a tool for
identifying genetic modifiers and small molecule drugs.
PMID- 24355815
TI - Allele frequency of hereditary equine regional dermal asthenia in American
Quarter horses in Brazil determined by quantitative real-time PCR with high
resolution melting analysis.
AB - Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder that
occurs in the American Quarter horse (AQH) and is caused by a c.115G>A missense
mutation in the peptidylprolyl isomerase B (PPIB) gene. Using a quantitative real
time PCR high resolution melting analysis genotyping assay for the PPIB mutation,
the estimated HERDA allele and carrier frequencies in a sample of Brazilian AQHs
were 2.9% and 5.8%, respectively.
PMID- 24355813
TI - Inflammatory pathways of seizure disorders.
AB - Epilepsy refers to a cluster of neurological diseases characterized by seizures.
Although many forms of epilepsy have a well-defined immune etiology, in other
forms of epilepsy an altered immune response is only suspected. In general, the
hypothesis that inflammation contributes to seizures is supported by experimental
results. Additionally, antiepileptic maneuvers may act as immunomodulators and
anti-inflammatory therapies can treat seizures. Triggers of seizure include a
bidirectional communication between the nervous system and organs of immunity.
Thus, a crucial cellular interface protecting from immunological seizures is the
blood-brain barrier (BBB). Here, we summarize recent advances in the
understanding and treatment of epileptic seizures that derive from a non
neurocentric viewpoint and suggest key avenues for future research.
PMID- 24355816
TI - Odors are expressible in language, as long as you speak the right language.
AB - From Plato to Pinker there has been the common belief that the experience of a
smell is impossible to put into words. Decades of studies have confirmed this
observation. But the studies to date have focused on participants from urbanized
Western societies. Cross-cultural research suggests that there may be other
cultures where odors play a larger role. The Jahai of the Malay Peninsula are one
such group. We tested whether Jahai speakers could name smells as easily as
colors in comparison to a matched English group. Using a free naming task we show
on three different measures that Jahai speakers find it as easy to name odors as
colors, whereas English speakers struggle with odor naming. Our findings show
that the long-held assumption that people are bad at naming smells is not
universally true. Odors are expressible in language, as long as you speak the
right language.
PMID- 24355817
TI - Ecological parameters influencing microbial diversity and stability of
traditional sourdough.
AB - The quality of some leavened, sourdough baked goods is not always consistent,
unless a well propagated sourdough starter culture is used for the dough
fermentation. Among the different types of sourdough used, the traditional
sourdough has attracted the interest of researchers, mainly because of its large
microbial diversity, especially with respect to lactic acid bacteria. Variation
in this diversity and the factors that cause it will impact on quality and is the
subject of this review. Sourdough microbial diversity is mainly caused by the
following factors: (i) sourdough is obtained through spontaneous, multi-step
fermentation; (ii) it is propagated using flour, whose nutrient content may vary
according to the batch and to the crop, and which is naturally contaminated by
microorganisms; and (iii) it is propagated under peculiar technological
parameters, which vary depending on the historical and cultural background and
type of baked good. In the population dynamics leading from flour to mature
sourdough, lactic acid bacteria (several species of Lactobacillus sp.,
Leuconostoc sp., and Weissella sp.) and yeasts (mainly Saccharomyces cerevisiae
and Candida sp.) outcompete other microbial groups contaminating flour, and
interact with each other at different levels. Ecological parameters qualitatively
and quantitatively affecting the dominant sourdough microbiota may be classified
into specific technological parameters (e.g., percentage of sourdough used as
inoculum, time and temperature of fermentation) and parameters that are not fully
controlled by those who manage the propagation of sourdough (e.g., chemical,
enzyme and microbial composition of flour). Although some sourdoughs have been
reported to harbour a persistent dominant microbiota, the stability of sourdough
ecosystem during time is debated. Indeed, several factors may interfere with the
persistence of species and strains associations that are typical of a given
sourdough: metabolic adaptability to the stressing conditions of sourdough,
nutritional and antagonistic interactions among microorganisms, intrinsic
robustness of microorganisms, and existence of a stable house microbiota. Further
studies have to be performed in order to highlight hidden mechanisms underlying
the microbial structure and stability of sourdough. The comprehension of such
mechanisms would be helpful to assess the most appropriate conditions that allow
keeping a given traditional sourdough as a stable microbial ecosystem, thus
preserving, during time, the typical traits of the resulting product.
PMID- 24355818
TI - Contribution of food additives to sodium and phosphorus content of diets rich in
processed foods.
AB - OBJECTIVE: Phosphorus-based food additives increase the total phosphorus content
of processed foods. However, the extent to which these additives augment total
phosphorus intake per day is unclear. DESIGN AND METHODS: To examine the
contribution of phosphorus-based food additives to the total phosphorus content
of processed foods, separate 4-day menus for a low-additive and additive-enhanced
diet were developed using Nutrition Data System for Research (NDSR) software. The
low-additive diet was designed to conform to U.S. Department of Agriculture
guidelines for energy and phosphorus intake (~2,000 kcal/day and 900 mg of
phosphorus per day), and it contained minimally processed foods. The additive
enhanced diet contained the same food items as the low-additive diet except that
highly processed foods were substituted for minimally processed foods. Food items
from both diets were collected, blended, and sent for measurement of energy and
nutrient intake. RESULTS: The low-additive and additive-enhanced diet provided
approximately 2,200 kcal, 700 mg of calcium, and 3,000 mg of potassium per day on
average. Measured sodium and phosphorus content standardized per 100 mg of food
was higher each day of the additive-enhanced diet as compared with the low
additive diet. When averaged over the 4 menu days, the measured phosphorus and
sodium contents of the additive-enhanced diet were 606 +/- 125 and 1,329 +/- 642
mg higher than the low-additive diet, respectively, representing a 60% increase
in total phosphorus and sodium content on average. When comparing the measured
values of the additive-enhanced diet to NDSR-estimated values, there were no
statistically significant differences in measured versus estimated phosphorus
contents. CONCLUSION: Phosphorus and sodium additives in processed foods can
substantially augment phosphorus and sodium intake, even in relatively healthy
diets. Current dietary software may provide reasonable estimates of the
phosphorus content in processed foods.
PMID- 24355820
TI - Time to revisit the role of renal dietitian in the dialysis unit.
PMID- 24355819
TI - Development of a predictive energy equation for maintenance hemodialysis
patients: a pilot study.
AB - OBJECTIVE: The study objectives were to explore the predictors of measured
resting energy expenditure (mREE) among a sample of maintenance hemodialysis
(MHD) patients, to generate a predictive energy equation (MHDE), and to compare
such models to another commonly used predictive energy equation in nutritional
care, the Mifflin-St. Jeor equation (MSJE). DESIGN AND METHODS: The study was a
retrospective, cross-sectional cohort design conducted at the Vanderbilt
University Medical Center. Study subjects were adult MHD patients (N = 67). Data
collected from several clinical trials were analyzed using Pearson's correlation
and multivariate linear regression procedures. Demographic, anthropometric,
clinical, and laboratory data were examined as potential predictors of mREE.
Limits of agreement between the MHDE and the MSJE were evaluated using Bland
Altman plots. The a priori alpha was set at P < .05. The main outcome measure was
mREE. RESULTS: The mean age of the sample was 47 +/- 13 years. Fifty participants
(75.6%) were African American, 7.5% were Hispanic, and 73.1% were males. Fat-free
mass (FFM), serum albumin (ALB), age, weight, serum creatinine (CR), height, body
mass index, sex, high-sensitivity C-reactive protein (CRP), and fat mass (FM)
were all significantly (P < .05) correlated with mREE. After screening for multi
collinearity, the best predictive model (MHDE-lean body mass [LBM]) of mREE
included (R(2) = 0.489) FFM, ALB, age, and CRP. Two additional models (MHDE-CRP
and MHDE-CR) with acceptable predictability (R(2) = 0.460 and R(2) = 0.451) were
derived to improve the clinical utility of the developed energy equation (MHDE
LBM). Using Bland-Altman plots, the MHDE over- and underpredicted mREE less often
than the MSJE. CONCLUSIONS: Predictive models (MHDE) including selective
demographic, clinical, and anthropometric data explained less than 50% variance
of mREE but had better precision in determining energy requirements for MHD
patients when compared with MSJE. Further research is necessary to improve
predictive models of mREE in the MHD population and to test its validity and
clinical application.
PMID- 24355821
TI - Vitamin D and anemia.
PMID- 24355822
TI - Add some spice to your life: the Caribbean way for dialysis patients.
PMID- 24355823
TI - Perimetric measurements with flicker-defined form stimulation in comparison with
conventional perimetry and retinal nerve fiber measurements.
AB - PURPOSE: We compared the results of flicker-defined form (FDF) perimetry with
standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness
measurements using spectral domain optical coherence tomography (OCT). METHODS: A
total of 64 healthy subjects, 45 ocular hypertensive patients, and 97 "early"
open-angle glaucoma (OAG) patients participated in this study. Definition of
glaucoma was based exclusively on glaucomatous optic disc appearance. All
subjects underwent FDF perimetry, SAP, and peripapillary measurements of the RNFL
thickness. The FDF perimetry and SAP were performed at identical test locations
(G1 protocol). Exclusion criteria were subjects younger than 34 years, SAP mean
defect (SAP MD) > 5 dB, eye diseases other than glaucoma, or nonreliable FDF
measurements. The correlations between the perimetric data on one hand and RNFL
thicknesses on the other hand were analyzed statistically. RESULTS: The age
corrected sensitivity values and the local results from the controls were used to
determine FDF mean defect (FDF MD). The FDF perimetry and SAP showed high
concordance in this cohort of experienced patients (MD values, R = -0.69, P <
0.001). Of a total of 42 OAG patients with abnormal SAP MD, 38 also displayed
abnormal FDF MD. However, FDF MD was abnormal in 28 of 55 OAG patients with
normal SAP MD. The FDF MD was significantly (R = -0.61, P < 0.001) correlated
with RNFL thickness with a (nonsignificantly) larger correlation coefficient than
conventional SAP MD (R = -0.48, P < 0.001). CONCLUSIONS: The FDF perimetry is
able to uncover functional changes concurrent with the changes in RNFL thickness.
The FDF perimetry may be an efficient functional test to detect early
glaucomatous nerve atrophy. (ClinicalTrials.gov number, NCT00494923.).
PMID- 24355824
TI - Continuous response of optic nerve head blood flow to increase of arterial blood
pressure in humans.
AB - PURPOSE: This study investigates the effect of increased ocular perfusion
pressure (OPP) on optic nerve head (ONH) hemodynamics. METHODS: In 21 healthy
subjects, the increase in arterial blood pressure (BP), measured continuously
using a pneumatic transcutaneous sensor, was produced by isometric exercise
consisting of 2 minutes of hand-gripping. ONH blood flow parameters-namely the
velocity (Vel), number (Vol), and flux (F) of red blood cells-were measured using
the laser Doppler flowmeter (LDF). RESULTS: In those 14 healthy subjects who
exhibited a similar increase in BP to handgrip superior to 30% of baseline BP,
group average increases of BP and OPP amounted to 34% +/- 3% (SEM) and 43% +/-
3%, respectively. The increase in F of 19% +/- 8%, resulting from an increase in
Vel (17% +/- 7%) and Vol (6% +/- 7%), was significantly less than predicted for a
passive autoregulatory response, as revealed also by the increase in vascular
resistance (R = OPP/F). Spearman test of linear correlations between F and time
during handgrip led to the identification of one group of eight subjects (with a
stable F) and one group of six subjects (with an increase in F). A closed-loop
gain (G) of the regulatory process, defined as G = 1 - {(F - Fbl)/Fbl}/{(OPP -
OPPbl)/OPPbl}, was found to be rather independent from the OPP, with an average
value 0.7 +/- 0.07. G was 0.83 +/- 0.06 for the group of eight subjects with
stable F and 0.3 +/- 0.15 for the group of six subjects with F increasing with
the OPP. CONCLUSIONS: The continuous recording of both BP and LDFs represents a
novel and more precise approach to the characterization of ONH hemodynamics
during isometric exercise, especially useful in the future for patients with
ocular diseases. The efficiency of the ONH blood flow autoregulation appears to
vary significantly between healthy subjects. (ClinicalTrials.gov number,
NCT00874913.).
PMID- 24355826
TI - Dynamic expiratory airway collapse and evaluation of collateral ventilation with
Chartis.
PMID- 24355825
TI - Development and validation of a lung transplant-specific disability
questionnaire.
AB - BACKGROUND: Lung transplant (LT) aims to extend survival and improve patient
centred outcomes (PCOs) by reducing disability and improving health-related
quality of life (HRQL). Few PCO instruments have been validated in LT
populations. We aimed to develop and validate a shortened version of the valued
life activities (VLA) disability scale specific to LT. METHODS: We used data from
140 subjects participating in an ongoing cohort study of LT. Subjects completed a
survey battery, including VLA items, and physical assessments before LT. To
develop a shortened LT-specific VLA (LT-VLA), we iteratively deleted items from a
longer 32-item VLA battery, retaining the instrument's conceptual framework,
scoring and performance characteristics. We evaluated LT-VLA validity by testing
correlations with a HRQL measure (Short Form-12 Physical Function (SF-12 PF)
subscale), forced vital capacity % (FVC%) predicted and 6 minute walk distance
(6MWD). Responsiveness was evaluated in 84 subjects who completed assessments
before and after LT. RESULTS: The 15-item LT-VLA scoring closely matched the
longer VLA (correlations >=0.96) and had excellent internal consistency
(Cronbach's alpha 0.92). The LT-VLA required only 3 min or less to administer.
The LT-VLA, measured as mean difficulty in performing each of the 15 activities
queried, correlated with FVC% predicted (r=-0.30), 6MWD (r=-0.38) and SF-12 PF
(r=-0.47) (all p<0.01). The LT-VLA mean difficulty was responsive to change from
before to after LT (63% improvement; effect size=1.60). CONCLUSIONS: The LT-VLA
is a short, easy to administer, valid and responsive disease-specific PCO
instrument that may be useful in clinical and research applications for lung
transplantation.
PMID- 24355827
TI - Emotions and memory in borderline personality disorder.
AB - Memory processes such as encoding, storage, and retrieval of information are
influenced by emotional content. Because patients with borderline personality
disorder (BPD) are particularly susceptible to emotional information, it is
relevant to understand whether such memory processes are altered in this patient
group. This systematic literature review collects current evidence on this issue.
Research suggests that emotional information interferes more strongly with
information processing and learning in BPD patients than in healthy controls. In
general, BPD patients do not seem to differ from healthy control subjects in
their ability to memorize emotional information, but they tend to have specific
difficulties forgetting negative information. Also, BPD patients seem to recall
autobiographical, particularly negative events with stronger arousal than healthy
controls, while BPD patients also show specific temporo-prefrontal alterations in
neural correlates. No substantial evidence was found that the current affective
state influences learning and memory in BPD patients any differently than in
healthy control subjects. In general, a depressive mood seems to both deteriorate
and negatively bias information processing and memories, while there is evidence
that dissociative symptoms impair learning and memory independently of stimulus
valence. This review discusses methodological challenges of studies on memory and
emotions in BPD and makes suggestions for future research and clinical
implications.
PMID- 24355828
TI - Ground-state and spin-wave dynamics in brownmillerite SrCoO(2.5)--a combined
hybrid functional and LSDA + U study.
AB - We theoretically investigate the ground-state magnetic properties of the
brownmillerite phase of SrCoO2.5. Strong correlations between Co d electrons are
treated within the local spin density approximations of density functional theory
(DFT) with Hubbard U corrections (LSDA+U), and results are compared with those
using the Heyd-Scuseria-Ernzerhof (HSE) functional. The parameters computed with
a U value of 7.5 eV are found to match closely to those computed within the HSE
functional. A G-type antiferromagnetic structure is found to be the most stable
one, consistent with experimental observation. By mapping the total energies of
different magnetic configurations onto a Heisenberg Hamiltonian, we compute the
magnetic exchange interaction parameters, J, between the nearest-neighbor Co
atoms. The J values obtained are then used to compute the spin-wave frequencies
and inelastic neutron scattering intensities. Among four spin-wave branches, the
lowest energy mode was found to have the largest scattering intensity at the
magnetic zone center, while the other modes become dominant at different momenta.
These predictions can be tested experimentally.
PMID- 24355829
TI - Development of a testing method for asbestos fibers in treated materials of
asbestos containing wastes by transmission electron microscopy.
AB - Appropriate treatment of asbestos-containing wastes is a significant problem. In
Japan, the inertization of asbestos-containing wastes based on new treatment
processes approved by the Minister of the Environment is promoted. A highly
sensitive method for testing asbestos fibers in inertized materials is required
so that these processes can be approved. We developed a method in which fibers
from milled treated materials are extracted in water by shaking, and are counted
and identified by transmission electron microscopy. Evaluation of this method by
using asbestos standards and simulated slag samples confirmed that the
quantitation limits are a few million fibers per gram and a few MUg/g in a sample
of 50mg per filter. We used this method to assay asbestos fibers in slag samples
produced by high-temperature melting of asbestos-containing wastes. Fiber
concentrations were below the quantitation limit in all samples, and total fiber
concentrations were determined as 47-170*10(-6) f/g. Because the evaluation of
treated materials by TEM is difficult owing to the limited amount of sample
observable, this testing method should be used in conjunction with bulk
analytical methods for sure evaluation of treated materials.
PMID- 24355830
TI - Flotability and flotation separation of polymer materials modulated by wetting
agents.
AB - The surface free energy, surface tension and contact angles were performed to
investigate the properties of wetting agents. Adsorption of wetting agents
changes wetting behavior of polymer resins. Flotability of polymer materials
modulated by wetting agents was studied, and wetting agents change significantly
flotability of polymer materials. The flotability decreases with increasing the
concentration of wetting agents, and the wetting ability is lignin sulfonate
(LS)>tannic acid (TA)>methylcellulose (MC)>triton X-100 (TX-100) (from strong to
weak). There is significant difference in the flotability between polymer resins
and plastics due to the presence of additives in the plastics. Flotation
separation of two-component and multicomponent plastics was conducted based on
the flotability modulated by wetting agents. The two-component mixtures can be
efficiently separated using proper wetting agent through simple flotation
flowsheet. The multicomponent plastic mixtures can be separated efficiently
through multi-stage flotation using TA and LS as wetting agents, and the purity
of separated component was above 94%, and the recovery was more than 93%.
PMID- 24355831
TI - Higher operating tables provide better laryngeal views for tracheal intubation.
AB - BACKGROUND: The present study was conducted to investigate the influence of
different operating table heights on the quality of laryngeal view and the
discomfort of the anaesthetist during enodotracheal intubation. METHODS: Eight
anaesthetists participated, to each of whom 20 patients were allocated. Before
induction of anaesthesia, the height of the operating table was adjusted to place
the patient's forehead at one of four landmarks on the anaesthetist's body (the
order being determined by block randomization with eight blocks): umbilicus
(Group U), lowest rib margin (Group R), xiphoid process (Group X), and nipple
(Group N). Next, the anaesthetist began the laryngoscopy and evaluated the grade
of laryngeal view. For this 'initial posture', the anaesthetist was not allowed
to adjust his or her posture (flexion or extension of the neck, lower back, knee,
and ankle). This laryngeal view was then re-graded after these constraints were
relaxed. At each posture, the anaesthetist's joint movements and discomfort
during mask ventilation or intubation were evaluated. RESULTS: The laryngeal view
before postural changes was better in Group N than in Group U (P=0.003). The
objective and subjective measurements of neck or lower back flexion during
intubation were higher in Group U than in Groups X and N (P<0.01 for each). The
improvement of laryngeal view resulting from postural changes correlated with the
anaesthetist's discomfort score before the postural change (P<0.01). CONCLUSIONS:
Higher operating tables (at the xiphoid process and nipple level of the
anaesthetist) can provide better laryngeal views with less discomfort during
tracheal intubation. TRIAL REGISTRY NUMBER: NCT01649973 (clinicaltrials.gov).
PMID- 24355832
TI - Radial artery applanation tonometry for continuous non-invasive arterial pressure
monitoring in intensive care unit patients: comparison with invasively assessed
radial arterial pressure.
AB - BACKGROUND: Radial artery applanation tonometry technology can be used for
continuous non-invasive measurement of arterial pressure (AP). The purpose of
this study was to evaluate this AP monitoring technology in intensive care unit
(ICU) patients in comparison with invasive AP monitoring using a radial arterial
catheter. METHODS: In 24 ICU patients (German university hospital), AP values
were simultaneously recorded on a beat-to-beat basis using radial artery
applanation tonometry (T-Line system; Tensys Medical, San Diego, CA, USA) and a
radial arterial catheter (contralateral arm). The primary endpoint of the study
was to investigate the accuracy and precision of the non-invasively assessed AP
measurements with the Bland-Altman method based on averaged 10 beat AP epochs
(n=2993 10 beat epochs). RESULTS: For mean AP (MAP), systolic AP (SAP), and
diastolic AP (DAP), we observed a bias (+/-standard deviation of the bias; 95%
limits of agreement; percentage error) of +2 mm Hg (+/-6; -11 to +15 mm Hg; 15%),
-3 mm Hg (+/-15; -33 to +27 mm Hg; 23%), and +5 mm Hg (+/-7; -9 to +19 mm Hg;
22%), respectively. CONCLUSIONS: In ICU patients, MAP and DAP measurements
obtained using radial artery applanation tonometry show clinically acceptable
agreement with invasive AP determination with a radial arterial catheter. While
the radial artery applanation tonometry technology also allows SAP measurements
with high accuracy, its precision for SAP measurements needs to be further
improved.
PMID- 24355833
TI - II. Retrograde cerebral venous gas embolism: are we missing too many cases?
PMID- 24355834
TI - Atlas of coronavirus replicase structure.
AB - The international response to SARS-CoV has produced an outstanding number of
protein structures in a very short time. This review summarizes the findings of
functional and structural studies including those derived from cryoelectron
microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray
crystallography, and incorporates bioinformatics predictions where no structural
data is available. Structures that shed light on the function and biological
roles of the proteins in viral replication and pathogenesis are highlighted. The
high percentage of novel protein folds identified among SARS-CoV proteins is
discussed.
PMID- 24355836
TI - Application of artificial neural network, fuzzy logic and decision tree
algorithms for modelling of streamflow at Kasol in India.
AB - The prediction of streamflow is required in many activities associated with the
planning and operation of the components of a water resources system. Soft
computing techniques have proven to be an efficient alternative to traditional
methods for modelling qualitative and quantitative water resource variables such
as streamflow, etc. The focus of this paper is to present the development of
models using multiple linear regression (MLR), artificial neural network (ANN),
fuzzy logic and decision tree algorithms such as M5 and REPTree for predicting
the streamflow at Kasol located at the upstream of Bhakra reservoir in Sutlej
basin in northern India. The input vector to the various models using different
algorithms was derived considering statistical properties such as auto
correlation function, partial auto-correlation and cross-correlation function of
the time series. It was found that REPtree model performed well compared to other
soft computing techniques such as MLR, ANN, fuzzy logic, and M5P investigated in
this study and the results of the REPTree model indicate that the entire range of
streamflow values were simulated fairly well. The performance of the naive
persistence model was compared with other models and the requirement of the
development of the naive persistence model was also analysed by persistence
index.
PMID- 24355835
TI - Studying Culicoides vectors of BTV in the post-genomic era: resources,
bottlenecks to progress and future directions.
AB - Culicoides biting midges (Diptera: Ceratopogonidae) are a major vector group
responsible for the biological transmission of a wide variety of globally
significant arboviruses, including bluetongue virus (BTV). In this review we
examine current biological resources for the study of this genus, with an
emphasis on detailing the history of extant colonies and cell lines derived from
C. sonorensis, the major vector of BTV in the USA. We then discuss the rapidly
developing area of genomic and transcriptomic analyses of biological processes in
vectors and introduce the newly formed Culicoides Genomics and Transcriptomics
Alliance. Preliminary results from these fields are detailed and finally likely
areas of future research are discussed from an entomological perspective
describing limitations in our understanding of Culicoides biology that may impede
progress in these areas.
PMID- 24355838
TI - Comparison of four types of membrane bioreactor systems in terms of shear stress
over the membrane surface using computational fluid dynamics.
AB - Membrane bioreactors (MBRs) have been used successfully in biological wastewater
treatment to solve the perennial problem of effective solids-liquid separation. A
common problem with MBR systems is clogging of the modules and fouling of the
membrane, resulting in frequent cleaning and replacement, which makes the system
less appealing for full-scale applications. It has been widely demonstrated that
the filtration performances in MBRs can be greatly improved with a two-phase flow
(sludge-air) or higher liquid cross-flow velocities. However, the optimization
process of these systems is complex and requires knowledge of the membrane
fouling, hydrodynamics and biokinetics. Modern tools such as computational fluid
dynamics (CFD) can be used to diagnose and understand the two-phase flow in an
MBR. Four cases of different MBR configurations are presented in this work, using
CFD as a tool to develop and optimize these systems.
PMID- 24355837
TI - Performance of sanitary sewer collection system odour control devices operating
in diverse conditions.
AB - Controlling odours from sanitary sewer systems is challenging as a result of the
expansive nature of these systems. Addition of oxidizing chemicals is often
practiced as a mitigation strategy. One alternative is to remove odorous
compounds in the gases vented from manholes using adsorptive media. In this
study, odour control devices located at manholes were observed to determine the
ability of these systems to reduce hydrogen sulphide from vented gases. The odour
control devices incorporated pressure regulation to control gas flow out of
manhole covers and adsorptive media to remove hydrogen sulphide in the vented
gases prior to release. Pressure regulation was accomplished using a variable
volume bladder and two pressure relief valves that permitted gas flow when
pressures exceeded 1.3 to 2.5 cm water column. The reduction in gas flow vented
from manholes was intended to extend the service life of the adsorptive media, as
compared with odour control devices that do not incorporate pressure modulation.
Devices were deployed at four locations and three adsorptive media were tested.
Although measured collection system hydrogen sulphide concentrations varied from
zero to over 1,000 ppm, the removal rates observed using odour control devices
were typically above 90%. The lower removal rates observed at one of the sites
(50.5 +/- 36.1%) appeared related to high gas flow rates being emitted at this
location. Activated carbon was used in most of the tests, although use of iron
media resulted in the highest removal observed: 97.8 +/- 3.6%. The expected
service life of the adsorptive media contained within the odour control devices
is a function of site-specific hydrogen sulphide concentrations and gas flow
rates. The units used in this study were in service for more than 8 to 12 months
prior to requiring media replacement.
PMID- 24355839
TI - Analytical solution for soil water redistribution during evaporation process.
AB - Simulating the dynamics of soil water content and modeling soil water evaporation
are critical for many environmental and agricultural strategies. The present
study aims to develop an analytical solution to simulate soil water
redistribution during the evaporation process. This analytical solution was
derived utilizing an exponential function to describe the relation of hydraulic
conductivity and water content on pressure head. The solution was obtained based
on the initial condition of saturation and an exponential function to model the
change of surface water content. Also, the evaporation experiments were conducted
under a climate control apparatus to validate the theoretical development.
Comparisons between the proposed analytical solution and experimental result are
presented from the aspects of soil water redistribution, evaporative rate and
cumulative evaporation. Their good agreement indicates that this analytical
solution provides a reliable way to investigate the interaction of evaporation
and soil water profile.
PMID- 24355840
TI - Odour reduction strategies for biosolids produced from a Western Australian
wastewater treatment plant: results from Phase I laboratory trials.
AB - This study investigated sources of odours from biosolids produced from a Western
Australian wastewater treatment plant and examined possible strategies for odour
reduction, specifically chemical additions and reduction of centrifuge speed on a
laboratory scale. To identify the odorous compounds and assess the effectiveness
of the odour reduction measures trialled in this study, headspace solid-phase
microextraction gas chromatography-mass spectrometry (HS SPME-GC-MS) methods were
developed. The target odour compounds included volatile sulphur compounds (e.g.
dimethyl sulphide, dimethyl disulphide and dimethyl trisulphide) and other
volatile organic compounds (e.g. toluene, ethylbenzene, styrene, p-cresol, indole
and skatole). In our laboratory trials, aluminium sulphate added to anaerobically
digested sludge prior to dewatering offered the best odour reduction strategy
amongst the options that were investigated, resulting in approximately 40%
reduction in the maximum concentration of the total volatile organic sulphur
compounds, relative to control.
PMID- 24355841
TI - Analysis on LID for highly urbanized areas' waterlogging control: demonstrated on
the example of Caohejing in Shanghai.
AB - Although a commonly applied measure across the United States and Europe for
alleviating the negative impacts of urbanization on the hydrological cycle, low
impact development (LID) has not been widely used in highly urbanized areas,
especially in rapidly urbanizing cities in developing countries like China. In
this paper, given five LID practices including Bio-Retention, Infiltration
Trench, Porous Pavement, Rain Barrels, and Green Swale, an analysis on LID for
highly urbanized areas' waterlogging control is demonstrated using the example of
Caohejing in Shanghai, China. Design storm events and storm water management
models are employed to simulate the total waterlogging volume reduction, peak
flow rate reduction and runoff coefficient reduction of different scenarios. Cost
effectiveness is calculated for the five practices. The aftermath shows that LID
practices can have significant effects on storm water management in a highly
urbanized area, and the comparative results reveal that Rain Barrels and
Infiltration Trench are the two most suitable cost-effective measures for the
study area.
PMID- 24355842
TI - A study to estimate the fate and transport of bacteria in river water from birds
nesting under a bridge.
AB - To investigate the effect of input parameters, such as the number of bridge
dwelling birds, decay rate of the bacteria, flow at the river, water temperature,
and settling velocity, a parametric study was conducted using a water quality
model developed with QUAL2Kw. The reach of the bacterial-impaired section from
the direct droppings of bridge-nesting birds at the Guadalupe River near
Kerrville, Texas was estimated using the model. The concentration of Escherichia
coli bacteria were measured upstream, below the bridge, and downstream of the
river for one-and-a-half years. The decay rate of the indicator bacteria in the
river water was estimated from the model using measured data, and was found to be
6.5/day. The study suggests that the number of bridge-dwelling birds, the decay
rate, and flow at the river have the highest impact on the fate and transport of
bacteria. The water temperature moderately affects the fate and transport of
bacteria, whereas, the settling velocity of bacteria did not show any significant
effect. Once the decay rates are estimated, the reach of the impaired section was
predicted from the model using the average flow of the channel. Since the decay
rate does not vary significantly in the ambient environment at this location, the
length of the impaired section primarily depends on flow.
PMID- 24355843
TI - Influences on the establishment and dominance of vegetation in stormwater
infiltration basins.
AB - Infiltration basins are widely used in urban environments as a technique for
managing and reducing the volume of stormwater. These basins can be spontaneously
colonized by wild plants, which can be used as bioindicators of edaphic
characteristics. As the basins are anthropogenic environments, the description of
plant biodiversity allows the determination of which species colonize such
environments and identification of the relationships between plants, basin type
and operation. Nineteen infiltration basins were selected according to their
catchment types (industrial, urban, agricultural). The dominant species were
identified and sampled. Rumex sp., Taraxacum sp. and Artemisia sp. are the three
types most represented (88, 61 and 55% respectively of the basins studied). Their
families and their respective orders are those most commonly found
(Caryophyllales, Asterales and Polygonaceae, Asteraceae). Poaceae is the family
grouping with the largest number of different species (11). Although each species
occupies only 1 or 2 basins, plants of this family occupy 61% of the basins.
Although the catchment characteristics of the 19 basins do not play a direct role
in the diversity of plant families, they can influence the presence or absence of
certain species. Thus, these plants can be used as bio-indicators of basin soil
and operating characteristics, such as sediment depths, inundation frequency and
duration.
PMID- 24355844
TI - Controlling chemical dosing for sulfide mitigation in sewer networks using a
hybrid automata control strategy.
AB - Chemicals such as magnesium hydroxide (Mg(OH)2) and iron salts are widely used to
control sulfide-induced corrosion in sewer networks composed of interconnected
sewer pipe lines and pumping stations. Chemical dosing control is usually non
automatic and based on experience, thus often resulting in sewage reaching the
discharge point receiving inadequate or even no chemical dosing. Moreover,
intermittent operation of pumping stations makes traditional control theory
inadequate. A hybrid automata-based (HA-based) control method is proposed in this
paper to coordinate sewage pumping station operations by considering their
states, thereby ensuring suitable chemical concentrations in the network
discharge. The performance of the proposed control method was validated through a
simulation study of a real sewer network using real sewage flow data. The
physical, chemical and biological processes were simulated using the well
established SeweX model. The results suggested that the HA-based control strategy
significantly improved chemical dosing control performance and sulfide mitigation
in sewer networks, compared to the current common practice.
PMID- 24355845
TI - Methodology of functionality selection for water management software and examples
of its application.
AB - When developing new software products and adapting existing software, project
leaders have to decide which functionalities to keep, adapt or develop. They have
to consider that the cost of making errors during the specification phase is
extremely high. In this paper a formalised approach is proposed that considers
the main criteria for selecting new software functions. The application of this
approach minimises the chances of making errors in selecting the functions to
apply. Based on the work on software development and support projects in the area
of water resources and flood damage evaluation in economic terms at CH2M HILL
(the developers of the flood modelling package ISIS), the author has defined
seven criteria for selecting functions to be included in a software product. The
approach is based on the evaluation of the relative significance of the functions
to be included into the software product. Evaluation is achieved by considering
each criterion and the weighting coefficients of each criterion in turn and
applying the method of normalisation. This paper includes a description of this
new approach and examples of its application in the development of new software
products in the are of the water resources management.
PMID- 24355846
TI - Performance of microbial fuel cells on removal of metronidazole.
AB - The microbial fuel cells (MFCs) are the focus of extensive investigation as one
of the promising technologies for renewable energy generation and wastewater
treatment. Two-chambered MFCs were designed to investigate the removal of
metronidazole and to quantify the effect of antibiotic on the efficacy of energy
generation. Using 1,000 mg glucose L(-1) containing different concentrations of
metronidazole (0, 10, 30, 50 mg L(-1)) as the fuels, the corresponding power
densities were 141.94, 99.23, 25.44, 16.26 mW m(-2), respectively. The adverse
effect on the performance of the MFCs was reversible. The removal of
metronidazole achieved 85.4% within 24 hours in MFCs, while only 35.2% in open
circuit. Current generation could account for the improved removal efficiency at
these tested concentration levels. The findings of this paper indicated that
antibiotics such as metronidazole could be removed in MFCs, which has
implications for general wastewater treatment.
PMID- 24355847
TI - Raising discharge standards leads to environmental problem shifting in China.
AB - The discharge standards for wastewater treatment plants (WWTPs) in China are
trending towards increasingly stringent nutrient removal requirements over recent
decades. However, the current paradigm for WWTPs has a singular focus on effluent
quality, seldom considering the broader environmental consequences of the
treatment required to meet these more stringent limits. In this article, the
operating data of 17 WWTPs with three different discharge standards were
collected. Using an inventory-type approach, greenhouse gas (GHG) emissions and
eutrophication potential (EP) of each plant were calculated. Results show
diminishing marginal returns in terms of pollution reduction as the level of
treatment increases, taking environmental influences into consideration.
Therefore, the strictest standards are not the most cost-effective ones in
current China. Rather than focusing strictly on point source dischargers and
requiring advanced treatments, regulatory agencies should reconsider their water
quality protection strategies.
PMID- 24355848
TI - Treatment on low carbon-to-nitrogen micro-polluted water by layered biological
aerated filter with floating and sunken media.
AB - In order to improve the TN removal efficiency on low carbon-to-nitrogen micro
polluted water, in this study, a layered biological aerated filter (L-BAF) was
built. The results showed that the removal efficiency for CODMn, NH3-N, and TN
was 71.6-90.3%, 99.8-99.9%, and 57.8-65.7%, respectively, when the C/N ratio was
kept at 3 and the volumetric flow rate was 0.072 m(3) d(-1). The L-BAF could
improve the TN removal efficiency by about 20% compared to a traditional process.
The L-BAF and traditional process removal efficiency for NH3-N and CODMn were
similar. The kinetic performance of the L-BAF indicated that the relationship of
CODMn removal efficiency with the influent CODMn concentration could be described
by ln(C/C0) = -(0.0023/Q0C0(0.9398))H.
PMID- 24355849
TI - Development of exobiopolymer-based biosensor for detection of phosphate in water.
AB - The present study was conducted to develop a biosensor by exploiting phosphate
binding capacity of exobiopolymer (EBP) produced by Acinetobacter sp. An
environmental isolate of EBP-producing Acinetobacter sp. was subjected to
transposon (Tn5) mutagenesis to overproduce EBP and afford improved phosphate
selectivity. A mutant producing the highest amount of EBP with high phosphate
binding capacity was selected for biosensor probe fabrication. Phosphate samples
were filtered through EBP-coated membranes and phosphate retained on membranes
was determined by molybdenum blue method. The color produced was read using a LED
690 nm/photodiode detection system linked to an amplifier and signals were
converted to appropriate phosphate concentrations. The biosensor had a limit of
detection of 0.5 mg/L and a limit of quantification 1 mg/L. The biosensor as well
as the probe were found to be stable for at least 28 days. In conclusion, we
believe that the biosensor may have applications in monitoring of wastewater and
environmental samples. Further, the enrichment of phosphate levels by EBP can
help in analysis of very low phosphate concentrations.
PMID- 24355850
TI - Hydrogen sulfide removal from sediment and water in box culverts/storm drains by
iron-based granules.
AB - A renewable granular iron-based technology for hydrogen sulfide removal from
sediment and water in box culverts and storm drains is discussed. Iron granules,
including granular ferric hydroxide (GFH), granular ferric oxide (GFO) and rusted
waste iron crusts (RWIC) embedded in the sediment phase removed aqueous hydrogen
sulfide formed from sedimentary biological sulfate reduction. The exhausted iron
granules were exposed to dissolved oxygen and this regeneration process recovered
the sulfide removal capacities of the granules. The recovery is likely
attributable to the oxidation of the ferrous iron precipitates film and the
formation of new reactive ferric iron surface sites on the iron granules and sand
particles. GFH and RWIC showed larger sulfide removal capacities in the sediment
phase than GFO, likely due to the less ordered crystal structures on their
surfaces. This study demonstrates that the iron granules are able to remove
hydrogen sulfide from sediment and water in box culverts and storm drains and
they have the potential to be regenerated and reused by contacting with dissolved
oxygen.
PMID- 24355851
TI - Nitrogen patterns in subsurface waters of the Yzeron stream: effect of combined
sewer overflows and subsurface-surface water mixing.
AB - Urbanization subjects streams to increased nitrogen loads. Therefore studying
nitrogen forms at the interface between urban stream and groundwater is important
for water resource management. In this study we report results on water
delta(18)O and nitrogen forms in subsurface waters of a stream (Yzeron, France).
The sites studied were located upstream and downstream of combined sewer
overflows (CSO) in a rural area and a periurban area, respectively. Water
delta(18)O allowed us to follow the mixing of subsurface water with surface
water. Dissolved organic nitrogen and organic carbon of fine sediment increased
by 20-30% between rural and periurban subsurface waters in the cold season, under
high flow. The highest nitrate levels were observed in rural subsurface waters in
the cold season. The lowest nitrate levels were found in periurban subsurface
waters in the warm season, under low flow. They corresponded to slow exchange of
subsurface waters with channel water. Thus reduced exchange between surface and
subsurface waters and organic-matter-rich input seemed to favor nitrate reduction
in the downstream, periurban, subsurface waters impacted by CSO.
PMID- 24355852
TI - Peracetic acid for secondary effluent disinfection: a comprehensive performance
assessment.
AB - The paper is a review of previous research on secondary effluent disinfection by
peracetic acid (PAA) integrated with new data about the effect of a preliminary
flash-mixing step. The process was studied at bench and pilot scale to assess its
performance for discharge in surface water and agricultural reuse (target
microorganisms: Escherichia coli and faecal coliform bacteria). The purposes of
the research were: (1) determining PAA decay and disinfection kinetics as a
function of operating parameters, (2) evaluating PAA suitability as a
disinfectant, (3) assessing long-term disinfection efficiency, (4) investigating
disinfected effluent biological toxicity on some aquatic indicator organisms
(Vibrio fischeri, Daphnia magna and Selenastrum capricornutum), (5) comparing PAA
with conventional disinfectants (sodium hypochlorite, UV irradiation). PAA
disinfection was capable of complying with Italian regulations on reuse (10
CFU/100 mL for E. coli) and was competitive with benchmarks. No regrowth
phenomena were observed, as long as needed for agricultural reuse (29 h after
disinfection), even at negligible concentrations of residual disinfectant. The
toxic effect of PAA on the aquatic environment was due to the residual
disinfectant in the water, rather than to chemical modification of the effluent.
PMID- 24355853
TI - Application of the analytic hierarchy process to the analysis of wastewater
nutrient recycling options: a case based on a group study of residents in the
city of Zurich.
AB - The recycling of anthropogenic nutrients derived from the wastewater management
systems is often characterized by a complex and uncertain scenario, due not only
to the nature of the process but also to the involvement of different stakeholder
groups. Over the past 10 years in Switzerland, policies regarding the use of
sewage sludge as fertilizer have gradually shifted to a ban on use in
agriculture. As a result, alternative methods for the recycling of anthropogenic
nutrients may play a relevant role in the near future. This paper uses the
analytic hierarchy process (AHP) to examine more closely the nutrient-recycling
dilemma by analysing the preferences of a group of German-speaking residents in
the city of Zurich for various management scenarios. Nutrient recycling by the
use of urine separation toilets and the BioCon treatment process are presented as
possible management alternatives in addition to current practice. The study shows
that AHP can incorporate the respondents' preferences and multiple objectives
when evaluating alternatives with different attributes.
PMID- 24355854
TI - Comparison of imidazolium ionic liquids and traditional organic solvents: effect
on activated sludge processes.
AB - Data concerning the biodegradability and ecotoxicity of ionic liquids (ILs)
obtained so far are insufficient in the context of IL removal from wastewater in
activated sludge systems. Thus, in this work the selected imidazolium ionic
liquids and two organic solvents (methanol and acetone) were tested with respect
to their influence on activated sludge processes, particularly on the morphology
of sludge flocs. The presence of ionic liquids with the chemical structure of 1
alkyl-3-methyl imidazolium bromide in wastewater did not deteriorate biological
wastewater treatment processes if their concentration was not higher than 5 mg l(
1). Regarding the structure of the ILs studied, the longer the alkyl substituent
was, the stronger the effect on sludge flocs. The highest decrease in activated
sludge floc area and biomass concentration was exerted by the ionic liquid with
the longest alkyl chain, i.e. 1-decyl-3-methylimidazolium bromide. The action of
both methanol and acetone on floc size, activated sludge concentration and
efficiency of organic pollutants removal was weaker compared to all tested 1
alkyl-3-methyl imidazolium bromides.
PMID- 24355856
TI - Desalination of oil sands process-affected water and basal depressurization water
in Fort McMurray, Alberta, Canada: application of electrodialysis.
AB - The high content of inorganic species in water used to extract bitumen from the
Alberta oil sands and in the groundwater below the oil sands is an increasing
environmental concern. These water matrices require treatment before they can be
reused or safely discharged. Desalination of the oil sands process-affected water
(OSPW) and groundwater, or basal depressurization water (BDW), can be
accomplished with deionization techniques such as electrodialysis (ED). In order
to achieve the effective ED treatment, OSPW and BDW were pretreated with
coagulation-flocculation-sedimentation to remove solid species and turbidity. We
demonstrated that a conductivity range for industrial reuse of OSPW and BDW can
be achieved with the ED treatment and showed the possibility of applying ED in
the oil sands industry. A continuous ED system that reuses the diluate stream as
a source for the concentrate stream was designed. The cost of a hypothetical ED
water treatment plant in Fort McMurray, Alberta, was estimated to be C$10.71 per
cubic meter of treated water.
PMID- 24355855
TI - Ammonium removal from wastewater via struvite pyrolysate recycling with Mg(OH)2
addition.
AB - Magnesium ammonium phosphate (MAP) pyrolysate recycling technology was
investigated with Mg(OH)2-mediated pyrolysis. The results revealed that the
removal ratio of ammonium was stable at about 75%, and could be increased to 79%
after additional acidolysis. The phosphate concentration in the supernate was low
at 2 mg/L. The optimum conditions for ammonia release were a 1:1 molar ratio of
Mg(OH)2:NH4(+), a heating temperature of 110 degrees C and a heating time of 3
h. With continual additions of Mg(OH)2 to release ammonia, magnesium phosphate
(Mg3(PO4)2) was suggested as a possible derivative. However, with Mg(OH)2
mediated pyrolysis, the growth and nucleation of MAP was inhibited during MAP
pyrolysate recycling.
PMID- 24355857
TI - Bacterial diversity in antibiotic wastewater treatment.
AB - The bacterial diversity of an antibiotic industrial wastewater treatment system
was analyzed to provide the information required for further optimization of this
process and for identification of bacterial strains that perform improved
degradation of antibiotic industrial wastewater. The total bacterial DNA of
samples collected at three stages (aeration, precipitation, and idle) during the
sequencing batch reactor (SBR) process were analyzed by polymerase chain reaction
denaturing gradient gel electrophoresis (PCR-DGGE) of the 16 s rDNA V3 regions.
Community analysis was conducted in terms of the richness value (S), the
dominance degree and the Shannon-Wiener diversity index (H). Rich bacterial
diversity was apparent in the aeration stage of the SBR process, and the number
of bands in the aeration stage was more abundant than that in the precipitation
and idle stages. The DGGE analysis showed 15 bands, six of which were uncultured
bacteria, and included one anaerobic and five aerobic bacteria. The microbial
community in the aeration stage was the most complex of the whole SBR process,
while the dominant bacteria differed in each reaction stage. These results
demonstrate the cyclical dynamic changes in the bacterial population during the
SBR process for the treatment of antibiotic industrial wastewater.
PMID- 24355858
TI - The evaluation of rainfall influence on combined sewer overflows characteristics:
the Berlin case study.
AB - The present study aims to explore the relationship between rainfall variables and
water quality/quantity characteristics of combined sewer overflows (CSOs), by the
use of multivariate statistical methods and online measurements at a principal
CSO outlet in Berlin (Germany). Canonical correlation results showed that the
maximum and average rainfall intensities are the most influential variables to
describe CSO water quantity and pollutant loads whereas the duration of the
rainfall event and the rain depth seem to be the most influential variables to
describe CSO pollutant concentrations. The analysis of partial least squares
(PLS) regression models confirms the findings of the canonical correlation and
highlights three main influences of rainfall on CSO characteristics: (i) CSO
water quantity characteristics are mainly influenced by the maximal rainfall
intensities, (ii) CSO pollutant concentrations were found to be mostly associated
with duration of the rainfall and (iii) pollutant loads seemed to be principally
influenced by dry weather duration before the rainfall event. The prediction
quality of PLS models is rather low (R2 < 0.6) but results can be useful to
explore qualitatively the influence of rainfall on CSO characteristics.
PMID- 24355859
TI - A field study to evaluate the impact of different factors on the nutrient
pollutant concentrations in green roof runoff.
AB - The objectives of this study are to investigate the impact of different factors
on the nutrient pollutant concentrations in green roof runoff and to provide
reference data for the engineering design of dual substrate layer green roofs.
The data were collected from eight different trays under three kinds of
artificial rains. The results showed that except for total phosphorus, dual
substrate layer green roofs behaved as a sink for most of the nutrient pollutants
(significant at p < 0.05), and the first-flush effect did not occur during the 27
simulated rain events. The results also revealed that the concentration of these
nutrient pollutants in the runoff strongly depended on the features of the
nutrient substrates used in the green roof and the depth of the adsorption
substrates. Compared with the influence of the substrates, the influence of the
plant density and drainage systems was small.
PMID- 24355860
TI - Taenia eggs in a stabilization pond system with poor hydraulics: concern for
human cysticercosis?
AB - The objective of this study is to compare the removal of Taenia eggs to the
removal of Ascaris eggs in a wastewater stabilization pond system consisting of
three ponds in series, where the hydraulic residence time distribution has been
characterized via a tracer study supported by computational fluid dynamics
modeling. Despite a theoretical hydraulic retention time of 30 days, the peak dye
concentration was measured in the effluent of the first pond after only 26 hours.
The smaller-sized Taenia eggs were detected in higher concentrations than Ascaris
eggs in the raw wastewater. Ascaris eggs were not detected in the pond system
effluent, but 45 Taenia eggs/L were detected in the system effluent. If some of
these eggs were of the species Taenia solium, and if the treated wastewater were
used for the irrigation of crops for human consumption, farmers and consumers
could potentially be at risk for neurocysticercosis. Thus, limits for Taenia eggs
in irrigation water should be established, and precautions should be taken in
regions where pig taeniasis is endemic. The results of this study indicate that
the theoretical hydraulic retention time (volume/flow) of a pond is not always a
good surrogate for helminth egg removal.
PMID- 24355861
TI - Removal of PCP-Na from aqueous systems using monodispersed pompon-like magnetic
nanoparticles as adsorbents.
AB - Novel monodispersed pompon-like magnetite/chitosan (Fe3O4/CS) composite
nanoparticles were synthesized by a solvothermal method and used as adsorbents
for the removal of toxic sodium pentachlorophenate (PCP-Na) from aqueous media.
The adsorption behavior of PCP-Na on Fe3O4/CS obeyed the Langmuir isotherm and
fitted the pseudo-second-order kinetics model. Thermodynamic parameters showed
that the adsorption process was exothermic and spontaneous. Moreover, the
adsorption was strongly pH-dependent. The results of XPS, thermodynamics, pH
dependent and desorption studies suggested that electrostatic attraction,
hydrogen bonding and pi-pi interactions were all believed to play a role in PCP
Na adsorption on Fe3O4/CS. Having a saturation magnetization of 22.2 emu . g(-1),
the Fe3O4/CS can be easily separated from water with magnets within 2 min. The
adsorption equilibrium was achieved quite rapidly (within 30 min) and the maximum
removal of PCP-Na (91.5%) was obtained at 25 degrees C and pH 6.5. The Fe3O4/CS
investigated can be used to remove PCP-Na and other contaminants from wastewater.
PMID- 24355862
TI - Ozone pretreatment of olive mill wastewaters (OMW) and its effect on OMW
biochemical methane potential (BMP).
AB - The possibility of coupling a physicochemical pretreatment (ozonation) with a
biological treatment (anaerobic digestion) was investigated for the case of olive
mill wastewaters (OMW). Batch ozonation experiments were performed in a glass
bubble reactor. The parameters which were tested included the ozone concentration
in the inlet gas stream, the reactor temperature and the composition of the
liquid medium in terms of raw or fractionated OMW used. In the sequel, ozone
pretreated OMW samples were tested for their biochemical methane potential (BMP)
under mesophilic conditions and these results were compared to the BMP of
untreated OMW. The ozonation process alone resulted in a 57-76% decrease of total
phenols and a 5-18% decrease of total carbohydrates contained in OMW, depending
on the experimental conditions. Nevertheless, the ozone-pretreated OMW exhibited
lower chemical oxygen demand removal and methane production during BMP testing
compared to the untreated OMW.
PMID- 24355863
TI - Improving calibration of two key parameters in Hydrologic Engineering Center
hydrologic modelling system, and analysing the influence of initial loss on flood
peak flows.
AB - Parameter calibration is a key and difficult issue for a hydrological model.
Taking the Jinjiang Xixi watershed of south-east China as the study area, we
proposed methods to improve the calibration of two very sensitive parameters,
Muskingum K and initial loss, in the Hydrologic Engineering Center hydrologic
modelling system (HEC-HMS) model. Twenty-three rainstorm flood events occurring
from 1972 to 1977 were used to calibrate the model using a trial-and-error
approach, and a relationship between initial loss and initial discharge for these
flood events was established; seven rainstorm events occurring from 1978 to 1979
were used to validate the two parameters. The influence of initial loss change on
different return-period floods was evaluated. A fixed Muskingum K value, which
was calibrated by assuming a flow wave velocity at 3 m/s, could be used to
simulate a flood hydrograph, and the empirical power-function relationship
between initial loss and initial discharge made the model more applicable for
flood forecasting. The influence of initial loss on peak floods was significant
but not identical for different flood levels, and the change rate of peak floods
caused by the same initial loss change was more remarkable when the return period
increased.
PMID- 24355864
TI - Myeloperoxidase directs properdin-mediated complement activation.
AB - Neutrophils and complement are key members of innate immunity. The alternative
pathway (AP) of complement consists of C3, factor B, factor D and properdin,
which amplifies AP activation. AP has been implicated in many neutrophil-mediated
diseases, such as anti-neutrophil cytoplasmic antibody-associated vasculitis. The
exact mechanism by which the AP and neutrophils interact remains largely
unstudied. We investigated the ability of the AP to interact with neutrophil
components which can be exposed and released upon activation. Our studies focused
on neutrophil enzymes, including myeloperoxidase (MPO), proteinase 3 (PR3),
azurocidin, elastase, lysozyme and cathepsin G. All enzymes except for azurocidin
were able to bind properdin. However, only MPO could induce C3 activation. MPO
mediated AP complement activation in the presence of MgEGTA compared to the EDTA
control. This activation resulted in C3 deposition and required properdin to
occur. Furthermore, we could show that MPO binds properdin directly, which then
serves as a focus for AP activation. In summary, properdin can directly interact
with neutrophil components. MPO demonstrates the ability to activate the AP which
is dependent on properdin. Finally, MPO is capable of inducing properdin
initiated C3 and C5b-9 deposition in vitro.
PMID- 24355865
TI - Effect of cabergoline on metabolism in prolactinomas.
AB - INTRODUCTION: Hyperprolactinemia has been implicated in the pathogenesis of
obesity and glucose intolerance and is reportedly associated with an impaired
metabolic profile. The current study aimed at investigating the effects of 12-
and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in
patients with prolactinomas. PATIENTS AND METHODS: 61 patients with prolactinomas
(13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 +/-
10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic
parameters were assessed at diagnosis and after 12 and 60 months of continuous
CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. RESULTS:
Compared to baseline, CAB induced a significant decrease in PRL with complete
normalization in 93% of patients after the 60-month treatment. At baseline, MetS
prevalence was significantly higher in patients with PRL above (34.5%) than in
those with PRL lower (12.5%) than the median (129 MUg/l, p = 0.03). MetS
prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p =
0.001) months compared to baseline (28.0%). At both evaluations the lipid profile
significantly improved compared to baseline. Fasting insulin and homeostatic
model assessment of insulin resistance significantly decreased after 1 year of
CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months
(p = 0.000). The visceral adiposity index significantly decreased after the 60
month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB
dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p =
0.022). CONCLUSIONS: CAB significantly reduces MetS prevalence and improves the
adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and
other metabolic parameters might reflect the direct effect of CAB.
PMID- 24355866
TI - Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak
investigation.
AB - BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe
lower respiratory tract infection in people. Previous studies suggested dromedary
camels were a reservoir for this virus. We tested for the presence of MERS-CoV in
dromedary camels from a farm in Qatar linked to two human cases of the infection
in October, 2013. METHODS: We took nose swabs, rectal swabs, and blood samples
from all camels on the Qatari farm. We tested swabs with RT-PCR, with
amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading
frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific
PCRs and obtained sequences were used for phylogentic analysis together with
sequences from the linked human cases and other human cases. We tested serum
samples from the camels for IgG immunofluorescence assay, protein microarray, and
virus neutralisation assay. FINDINGS: We obtained samples from 14 camels on Oct
17, 2013. We detected MERS-CoV in nose swabs from three camels by three
independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment
(940 nucleotides) and a 4.2 kb concatenated fragment were very similar to the
MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr
Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs,
but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding
antibodies that correlated well with the presence of neutralising antibodies to
MERS-CoV. INTERPRETATION: Our study provides virological confirmation of MERS-CoV
in camels and suggests a recent outbreak affecting both human beings and camels.
We cannot conclude whether the people on the farm were infected by the camels or
vice versa, or if a third source was responsible. FUNDING: European Union
projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and
the VIRGO consortium.
PMID- 24355867
TI - Identification of MERS-CoV in dromedary camels.
PMID- 24355868
TI - Development of a quantitative PCR (qPCR) for Giardia and analysis of the
prevalence, cyst shedding and genotypes of Giardia present in sheep across four
states in Australia.
AB - A novel quantitative PCR (qPCR) for Giardia at the glutamate dehydrogenase (gdh)
locus was developed and validated. The qPCR was used to screen a total of 3412
lamb faecal samples collected from approximately 1189 lambs at three sampling
periods (weaning, post-weaning and pre-slaughter) from eight farms across South
Australia (SA), New South Wales (NSW), Victoria (Vic) and Western Australia (WA).
The overall prevalence was 20.2% (95% CI 18.9-21.6) and of the 690 positives, 473
were successfully typed. In general, the prevalence of Giardia varied widely
across the different farms with the highest prevalence in one WA farm (42.1%) at
pre-slaughter sampling and the lowest prevalence in one Victorian farm (7.2%) at
weaning. The range of cyst shedding at weaning, post-weaning and pre-slaughter
overall across all states was 63-1.3*10(9) cysts g(-1) (median=1.7*10(4)), 63
1.1*10(9) cysts g(-1) (median=9.6*10(3)), 63-4.7*10(9) cysts g(-1)
(median=8.1*10(4)) respectively. Assemblage specific primers at the triose
phosphate isomerase (tpi) locus identified assemblage A in 22.4% (106/473) of
positive samples typed, assemblage E in 75.9% (359/473) and mixed A and E
assemblages in 1.7% (8/473) of samples. A subset of representative samples from
the 8 farms (n=32) were typed at both the gdh and beta-giardin loci and confirmed
these results and identified sub-assemblage AII in 16 representative assemblage A
isolates across the 8 farms. This demonstrates a prevalence of Giardia previously
not recognised in Australian sheep, highlighting a need for further research to
quantify the production impacts of this protozoan parasite.
PMID- 24355869
TI - Social perceptions of orthodontic retainer wear.
AB - SUMMARY BACKGROUND/OBJECTIVES: Social perceptions are influenced by dental
appearance. The aim of this study was to determine whether social perceptions of
a young adult are influenced by orthodontic retainer design and appearance.
MATERIALS AND METHODS: Following ethical approval, a pilot-tested questionnaire
study was conducted with 402 third-level students from the Republic of Ireland.
Each participant was invited to look at one randomly allocated colour full-face
smiling photograph of a young adult male or a young adult female wearing one of
five maxillary retainers and asked to make judgements on a Likert scale
concerning the subject's social competence (SC), psychological adjustment (PA),
intellectual ability (IA), and attractiveness. Five computer-modified
standardized photographs of each subject wearing each of the following retainers
were used: Essix, conventional Hawley, acrylated Hawley, and Begg; an image with
no retainer simulated a bonded retainer (BR) appearance. Statistical analyses
were performed in SAS(r) (Version 9.2). RESULTS: No significant differences were
found between the retainers for SC (P = 0.6741) and PA (P = 0.7217). In the male
subject only, greater perceived IA was found with the BR appearance compared to
that of the conventional Hawley (P = 0.0018) or the acrylated Hawley (P =
0.0016). The BR appearance was perceived as more attractive than that of the Begg
retainer (P = 0.0103). LIMITATIONS: In this study, participants were required to
make arbitrary judgements on a single image, which may not be a complete
representation of a person. CONCLUSIONS/IMPLICATIONS: Social perceptions were
found to be influenced by retainer design and appearance. This may be a factor in
determining retainer choice.
PMID- 24355870
TI - A comparison of tapered and cylindrical miniscrew stability.
AB - OBJECTIVES: This study compared the stability of tapered miniscrews with
cylindrical miniscrews. MATERIALS/METHODS: One hundred and five tapered and 122
cylindrical self-drilling miniscrews were placed into the maxillary and
mandibular buccal alveolar areas of 132 patients (43 males and 89 females). The
insertion torque and removal torque were measured and Periotest values (PTVs)
were recorded at implantation. RESULTS: The success rates of the tapered and
cylindrical miniscrews examined were similar. In the maxilla, the insertion
torque of the tapered miniscrews (8.3 Ncm) was significantly higher than that of
the cylindrical miniscrews (6.3 Ncm) (P < 0.05). The PTVs of the tapered
miniscrews were statistically significantly lower in the maxilla (P < 0.05). The
removal torque values showed no significant difference between the tapered and
cylindrical miniscrews in the upper and lower buccal areas (P > 0.05).
CONCLUSIONS: Tapered miniscrews had higher initial stability when compared to
cylindrical miniscrews, whereas the clinical success rates and removal torques
were similar between the two designs. The long-term stability is not directly
affected by the miniscrew design.
PMID- 24355871
TI - Radiographic assessment of external root resorption associated with jackscrew
based maxillary expansion therapies: a systematic review.
AB - OBJECTIVE: To evaluate in adolescents and young adults if jackscrew-based
maxillary expansion therapies result in external root resorption as measured in
vivo via any radiological method. METHODS: The authors conducted a systematic
search of several electronic databases (MEDLINE, EMBASE, PubMed, Scopus, CINAHL,
Evidence Based Medicine Reviews, LILACS) with the assistance of a senior
librarian specialized in Health Sciences database searches through 25 August
2013, as well as a limited grey-literature search (Google Scholar). Human, in
vivo studies of adolescents or young adults with transverse maxillary deficiency
undergoing non-surgical maxillary expansion therapy through the use of a
jackscrew-based maxillary expander with a radiographical assessment of root
resorption were selected for full article review. Additionally, manual searches
of reference lists of relevant articles were completed to identify additional
publications not identified by electronic searches. The lowest levels of evidence
accepted for inclusion were case-control studies or consecutively treated series
of cases. Two authors independently reviewed and extracted data from selected
studies. RESULTS: A total of 83 original articles were identified from the
electronic database and limited grey-literature searches. Once selection criteria
were applied, only three articles satisfied all inclusion criteria, and
individual analysis of the selected articles was undertaken. CONCLUSIONS: Two
dimensional periapical radiographs do not fully reveal the amount of external
root resorption associated with maxillary expansion therapy, except for frank
apical root resorption. Three-dimensional cone-beam computed tomography
radiography displays statistically significant root volume loss associated with
maxillary expansion therapy. However, when considering volume-loss percentages,
no statistical significance was found.
PMID- 24355872
TI - A histomorphometric and radiographic study of replanted human premolars.
AB - SUMMARY OBJECTIVES: The purpose of this study was to investigate time-related
dental tissue reactions to tooth replantation in mature and immature human
premolars by histomorphometric and radiographic methods. MATERIAL AND METHODS:
Sixty premolars were extracted, immediately replanted (T0), and left without
intervention for 1, 2, 3, 6, 12, and 24 weeks before re-extraction (T1).
Periapical radiographs were taken at T0 and T1 in all groups except for the 24
week group. Paraffin-embedded teeth were sectioned buccolingually at 5 um,
stained with haematoxylin-eosin, and prepared for histological analysis. Root
resorption, tertiary dentine, and root and crown length were recorded and
compared on both radiographs and paraffin sections. RESULTS: Initial degeneration
of the odontoblast layer and disturbance of vasculature and normal architecture
of the pulp were seen in both mature and immature teeth within the first 3 weeks.
Revascularization and tertiary dentine formation was visible on histological
sections in immature teeth at 6 weeks. After 24 weeks, most immature teeth had
pulps partly or completely obliterated. Abundant tertiary dentine observed on
histological slides was not easily seen on periapical radiographs. Likewise,
surface root resorption found in both immature and mature teeth was not visible
on the radiographs up to 6 weeks after replantation. CONCLUSION: Within the
limits of this study it can be concluded that the dental pulp of immature teeth
has the ability to regenerate and produce tertiary dentine after replantation.
Root resorptions and tertiary dentine seen on histological sections are not
visible on corresponding radiographs 6 and 12 weeks after replantation.
PMID- 24355873
TI - Thrombolysis in acute stroke patients with cerebral small vessel disease.
AB - BACKGROUND: Thrombolytic treatment is of proven benefit in acute ischemic stroke.
The term cerebral small vessel disease (SVD) refers to a group of pathological
processes affecting the small arteries, arterioles, venules and capillaries of
the brain, and encompasses both ischemic and hemorrhagic lesions. Lacunar stroke,
an expression of SVD, is associated with an unfavorable long-term prognosis for
an increased risk of death, recurrent stroke and cognitive dysfunction.
Nonetheless, the efficacy and safety of intravenous thrombolysis in patients with
lacunar stroke has been debated for two main reasons. First, among all ischemic
stroke subtypes, lacunar strokes have been considered the most benign. Second,
the efficacy of a pharmacological reperfusion has been questioned given the
absence of a clear demonstration of thrombosis. Intracerebral hemorrhage (ICH)
remains the most devastating and unpredictable complication related to
thrombolysis, and neuroimaging evidence of SVD is nowadays recognized as one of
the risk factors for thrombolysis-related ICH. SUMMARY: This review is structured
in two parts dealing with the questions whether or not patients with lacunar
stroke or SVD should be treated with thrombolysis. In the first part, we revised
the literature concerning the efficacy of thrombolysis in patients with acute
lacunar stroke. We included two types of studies: those in which patients with
lacunar stroke receiving recombinant human tissue plasminogen activator (rt-PA)
were compared with lacunar stroke patients receiving placebo, and those in which
a comparison was made among different stroke subtype patients treated with rt-PA.
In the second part, we reviewed the available evidence on the risk of ICH in
patients treated with thrombolysis for ischemic stroke and presenting with
neuroimaging evidence of SVD such as white matter lesions (WML) and cerebral
microbleeds. We further questioned the extent to which WML and microbleeds could
be used as reliable predictors of ICH and the feasibility of their detection in
an acute setting. KEY MESSAGES: The studies herein reviewed show that
thrombolysis is an effective treatment in acute lacunar stroke, and that the
presence of cerebral SVD increases the risk of ICH during thrombolysis but does
not represent an absolute exclusion criterion. In the future, it can be assumed
that the use of MRI on a routine basis might lead to a better quantitative
definition of SVD and its correlates, permitting a step forward in thrombolysis
decision making.
PMID- 24355874
TI - Early angiopoietin-2 levels after onset predict the advent of severe
pancreatitis, multiple organ failure, and infectious complications in patients
with acute pancreatitis.
AB - BACKGROUND: Acute pancreatitis is a severe condition that requires early
identification of patients at risk of developing potentially lethal
complications. Current clinical scoring systems and biochemical parameters are
insufficient. In this study, we aimed to assess whether early plasma Angiopoietin
2 (Ang-2) is associated with adverse outcomes in patients with predicted severe
acute pancreatitis (SAP). STUDY DESIGN: This analysis is a substudy of the
PROPATRIA trial (probiotics vs placebo in patients with predicted SAP). The Ang-2
levels were measured prospectively in plasma in the first 5 days after admission
in 115 patients. RESULTS: Early Ang-2 levels were higher in patients who
developed SAP: 6.4 vs 3.1 MUg/L (p < 0.001) and also were higher in patients who
developed multiorgan failure in the first week (p = 0.001) and after the first
week (p = 0.049). Furthermore, high Ang-2 levels were associated with infectious
complications in the first week (p < 0.001) and after the first week (p < 0.001).
Finally, plasma Ang-2 was significantly higher in patients who died (p < 0.001)
and in patients who developed bowel ischemia (p < 0.001). As a predictor of
adverse outcomes, plasma Ang-2 was superior to a number of current scores, such
as the APACHE II score, the Imrie score, C-reactive protein, lipopolysaccharide
binding protein, and procalcitonin. CONCLUSIONS: In the setting of this
randomized controlled trial, early plasma Ang-2 was found to be an accurate
predictor of SAP, multiorgan failure, and infectious complications. As a
biomarker, it did outperform all of the investigated conventional predictors that
are currently used in clinical practice.
PMID- 24355875
TI - The electronic Trauma Health Record: design and usability of a novel tablet-based
tool for trauma care and injury surveillance in low resource settings.
AB - BACKGROUND: Ninety percent of global trauma deaths occur in under-resourced or
remote environments, with little or no capacity for injury surveillance. We
hypothesized that emerging electronic and web-based technologies could enable
design of a tablet-based application, the electronic Trauma Health Record (eTHR),
used by front-line clinicians to inform trauma care and acquire injury
surveillance data for injury control and health policy development. STUDY DESIGN:
The study was conducted in 3 phases: 1. Design of an electronic application
capable of supporting clinical care and injury surveillance; 2. Preliminary
feasibility testing of eTHR in a low-resource, high-volume trauma center; and 3.
Qualitative usability testing with 22 trauma clinicians from a spectrum of high-
and low-resource and urban and remote settings including Vancouver General
Hospital, Whitehorse General Hospital, British Columbia Mobile Medical Unit, and
Groote Schuur Hospital in Cape Town, South Africa. RESULTS: The eTHR was designed
with 3 key sections (admission note, operative note, discharge summary), and 3
key capabilities (clinical checklist creation, injury severity scoring, wireless
data transfer to electronic registries). Clinician-driven registry data
collection proved to be feasible, with some limitations, in a busy South African
trauma center. In pilot testing at a level I trauma center in Cape Town, use of
eTHR as a clinical tool allowed for creation of a real-time, self-populating
trauma database. Usability assessments with traumatologists in various settings
revealed the need for unique eTHR adaptations according to environments of
intended use. In all settings, eTHR was found to be user-friendly and have ready
appeal for frontline clinicians. CONCLUSIONS: The eTHR has potential to be used
as an electronic medical record, guiding clinical care while providing data for
injury surveillance, without significantly hindering hospital workflow in various
health-care settings.
PMID- 24355876
TI - Emergency access to neurosurgical care for patients with traumatic brain injury.
AB - BACKGROUND: Traumatic brain injury (TBI) is one of the most common causes of
injury-related morbidity and mortality. Access to neurosurgical services is
critical to optimal outcomes through reduction of secondary injury. We sought to
evaluate variations in access to neurosurgical care across a regional trauma
system. STUDY DESIGN: This is a population-based retrospective cohort study of
patients who sustained isolated severe TBI from 2005 to 2009. Administrative
datasets capturing all emergency department visits and hospitalizations were
linked deterministically. Differences between access to a trauma center (TC),
defined as direct transport from scene or transfer from a nontrauma center (NTC)
as opposed to no access, were evaluated; this included patient level determinants
of access to TC and delineation of mortality differences between TC and NTC care.
Transfer patterns from NTC to TC were also evaluated. RESULTS: We identified
9,448 patients with isolated severe TBI. Almost two-thirds (60%, n = 5,701)
received initial care at an NTC. Of these patients, 30% (n = 1,737) were
subsequently transferred to a TC. Thirty-day mortality rates of patients treated
at a TC vs NTC were 19% vs 18%, respectively (p = 0.19). Among patients younger
than 65 years, 67% received TC care; only 41% of patients older than 65 were
treated at a TC (p < 0.01). Mechanism, age, brain hemorrhage, and injury severity
were associated with TC care. CONCLUSIONS: Considerable variation in delivery of
initial care to TBI patients was identified. Factors such as age and injury
characteristics were associated with TC access. Because early TC care in TBI
confers survival benefits, the demonstrated variability necessitates improvements
in access to care for patients with severe head injuries.
PMID- 24355877
TI - Complications of pediatric cholecystectomy: impact from hospital experience and
use of cholangiography.
AB - BACKGROUND: Complications after cholecystectomy in children are poorly
characterized. The aim of this study was to assess risk factors for major
surgical complications for children undergoing cholecystectomy. STUDY DESIGN: All
children 4 to 18 years old with gallbladder disease who underwent cholecystectomy
from 1999 to 2006 were identified from the California Patient Discharge Database.
Patient, hospital, and surgical factors were analyzed using multivariate logistic
regression analysis to identify factors predictive of bile duct injury (BDI) and
postoperative ERCP. RESULTS: A cohort of 6,931 children treated at 360 hospitals
was evaluated. Most children underwent cholecystectomy at a non-children's
hospital (84%). Intraoperative cholangiogram (IOC) was performed in 2,053 (30%)
children. Of 5,101 children tracked through the year after cholecystectomy, 153
(3%) required readmission for surgical complications. Bile duct injury occurred
in 25 (0.36%) children, and postoperative ERCP was performed in 711 (10%)
children. Older age (odds ratio = 0.80; 99% CI, 0.67-0.95) was associated with
decreased risk of BDI. Increased hospital tendency for routine IOC use was
associated with increased likelihood of BDI (odds ratio = 12.92; 99% CI, 1.31
127.15). Receiving surgical care at a children's hospital was associated with a
decreased likelihood of postoperative ERCP (odds ratio = 0.39; 99% CI, 0.23
0.66). As anticipated, choledocholithiasis, cholecystitis, IOC, and laparoscopic
cholecystectomy were associated with increased risk of postoperative ERCP (p <
0.01). CONCLUSIONS: Serious complications and readmissions from pediatric
cholecystectomy are uncommon. Surgeons performing cholecystectomy in young
children must have an elevated concern about BDI. Routine IOC or surgical volume
might not be helpful in lowering BDI rates.
PMID- 24355878
TI - Noise or silence in the operating room?
PMID- 24355879
TI - Choosing a better technique for midline abdominal closure.
PMID- 24355881
TI - Estrogen receptor beta-mediated proliferative inhibition and apoptosis in human
breast cancer by calycosin and formononetin.
AB - BACKGROUND: Calycosin and formononetin are two main components of isoflavones. In
our previous studies, we have respectively reported their antitumor activities on
breast cancer cell MCF-7. To further investigate the feasibility of isoflavones
in clinically treating breast carcinoma, here we specifically focused on the
comparison between calycosin and formononetin, along with the relevant mechanism.
METHODS: ER-positive (MCF-7, T-47D) and ER-negative breast cancer cells (MDA-231,
MDA-435) were respectively treated with calycosin or formononetin. Cell
proliferation and apoptosis were measured by MTT assay and flow cytometry. mRNA
levels of ER beta (ERbeta) and miR-375 were quantifed by real-time PCR.
Expression of ERbeta and insulin-like growth factor 1 receptor (IGF-1R), and
activation of poly (ADP-ribose) polymerase 1 (PARP-1) were determined by Western
blotting. RESULTS: Both calycosin and formononetin impaired proliferation and
triggered apoptosis of ER-positive breast cancer cells (MCF-7, T-47D) in a time-
and dose-dependent manner, especially in the treatment with calycosin. However,
no such effect was observed in ER-negative breast cancer cells, indicating the
correlation between isoflavones-induced inhibitory effect and ERs. Thus calycosin
and most sensitive MCF-7 cells were used to study the relevant signaling pathway.
After the treatment of calycosin, ERbeta expression was significantly increased
in MCF-7 cells, followed by decrease of IGF-1R, activation of PARP-1 cleavage and
downregulation of miR-375. CONCLUSION: Calycosin has an advantage on inhibiting
breast cancer growth in comparison with formononetin, which is obtained by ERbeta
mediated regulation of IGF-1R signaling pathways and miR-375 expression.
PMID- 24355882
TI - Tunable magnetic orders in CePd2As2-xPx.
AB - We report the successful synthesis of the polycrystalline compounds CePd2As2-xPx
(0 <= x <= 2) and their physical properties by measuring transport, magnetic and
thermodynamic behaviors as a function of temperature and/or magnetic field.
Powder x-ray diffraction indicates that CePd2As2-xPx crystallizes in the ThCr2Si2
type tetragonal structure. CePd2As2 exhibits a moderate Sommerfeld coefficient of
gamma ~ 88 mJ mol(-1) K(-2), and undergoes an antiferromagnetic (AFM) transition
at the Neel temperature TN ~ 15 K. Upon substituting As with P, the TN is nearly
unchanged up to x ? 0.6, while a ferromagnetic (FM) transition develops below TN
for x ? 0.4. The Curie temperature TC increases with increasing x and eventually
merges with the AFM transition at x ? 0.6. With further increase of x, the system
follows typical FM behaviors and its TC monotonically increases and reaches TC ~
28 K in CePd2P2. Moreover, a metamagnetic transition is observed in the As-rich
samples, but vanishes for x >= 0.4. Such a tunable magnetic ground state may
provide an opportunity to explore the possible quantum critical behavior in
CePd2As2-xPx.
PMID- 24355884
TI - Elimination of admission hypothermia in preterm very low-birth-weight infants by
standardization of delivery room management.
AB - CONTEXT: Temperature instability is a serious but potentially preventable
morbidity in preterm infants. Admission temperatures below 36 degrees C are
associated with increased mortality and late onset sepsis. OBJECTIVE: The goal of
our quality-improvement effort was to increase preterm infants' admission
temperatures to above 36 degrees C by preventing heat loss in the immediate
postnatal period. DESIGN: This quality-improvement initiative used the rapid
cycle Plan-Do-Study-Act approach. Preterm infants born at less than 33 weeks'
gestation with very low birth weight less than 1500 g who were born at a Regional
Level III Neonatal Intensive Care Unit (NICU) in San Jose, CA, were enrolled. Our
intervention involved standardizing the management of thermoregulation from
predelivery through admission to the NICU. Data on admission temperature were
collected prospectively. MAIN OUTCOME MEASURES: The primary outcome measure was
hypothermia, defined as temperature below 36 degrees C on admission to the NICU.
RESULTS: The hypothermia rate was reduced from 44% in early 2006 to 0% by 2009.
There was a slight increase to 6% in 2010. Subsequently, with further real-time
feedback, we were able to sustain 0% hypothermia through 2011. Our hypothermia
rate remained substantially lower than state and national hypothermia benchmarks
that have shown moderate improvement over the same period. CONCLUSION: We reduced
hypothermia in very low-birth-weight infants using a standardized protocol,
multidisciplinary team approach, and continuous feedback. Sustaining improvement
is a challenge that requires real-time progress evaluation of outcomes and
ongoing staff education.
PMID- 24355883
TI - Accuracy and implications of percutaneous renal biopsy in the management of renal
masses.
AB - INTRODUCTION: Percutaneous renal biopsy in patients with renal masses is
increasing. We investigated the accuracy of percutaneous renal mass biopsy
results in patients undergoing evaluation of solid renal masses. METHODS: A
retrospective review was performed of patients in the Kaiser Permanente Southern
California Region who underwent computed tomography or ultrasound-guided
percutaneous renal biopsy of a solid renal mass between January 2005 and December
2009. Patients were stratified by size of mass (<= 4 cm vs > 4 cm). Initial
biopsy results were correlated with final pathology specimens after extirpation.
RESULTS: Medical records of 126 patients (129 renal units with 132 biopsies) were
reviewed. Initial diagnostic biopsies revealed 87 (66%) malignant, 38 (29%)
benign, and 7 (5%) nondiagnostic lesions. Sixty-three patients (50%) ultimately
underwent extirpative surgery (23 partial and 40 radical nephrectomies). Of these
patients, the diagnostic accuracy of the initial percutaneous renal mass biopsy
was 76%, with an overall sensitivity and specificity of 75.4% and 100%,
respectively. The biopsy concordance to final histologic tumor subtype was 93%.
Larger tumor size (odds ratio [OR], 2.20; 95% confidence interval [CI], 0.55 to
8.88) and increasing number of biopsies (OR, 2.50; 95% CI, 0.59 to 10.69) were
associated with increasing accuracy of a biopsy result to predict cancer;
however, these associations were not statistically significant. CONCLUSION:
Percutaneous renal mass biopsy is diagnostically accurate and has good
sensitivity, specificity, and concordance with final pathologic renal cell
carcinoma subtype. This diagnostic modality can assist in management of select
renal masses as treatment options are expanding.
PMID- 24355885
TI - Mental health practice and attitudes of family physicians can be changed!
AB - OBJECTIVES: An adult mental health module was developed in British Columbia to
increase the use of evidence-based screening and cognitive behavioral self
management tools as well as medications that fit within busy family physician
time constraints and payment systems. Aims were to enhance family physician
skills, comfort, and confidence in diagnosing and treating mental health patients
using the lens of depression; to improve patient experience and partnership; to
increase use of action or care plans; and to increase mental health literacy and
comfort of medical office assistants. METHODS: The British Columbia Practice
Support Program delivered the module using the Plan-Do-Study-Act cycle for
learning improvement. Family physicians were trained in adult mental health, and
medical office assistants were trained in mental health first aid. Following
initial testing, the adult mental health module was implemented across the
province. RESULTS: More than 1400 of the province's 3300 full-service family
physicians have completed or started training. Family physicians reported high to
very high success implementing self-management tools into their practices and the
overall positive impact this approach had on patients. These measures were
sustained or improved at 3 to 6 months after completion of the module. An Opening
Minds Survey for health care professionals showed a decrease in stigmatizing
attitudes of family physicians. CONCLUSIONS: The adult mental health module is
changing the way participants practice. Office-based primary mental health care
can be improved through reimbursed training and support for physicians to
implement practical, time-efficient tools that conform to payment schemes. The
module provided behavior-changing tools that seem to be changing stigmatizing
attitudes towards this patient population. This unexpected discovery has piqued
the interest of stigma experts at the Mental Health Commission of Canada.
PMID- 24355886
TI - Use of portable ultrasound machine for outpatient orthopedic diagnosis: an
implementation study.
AB - INTRODUCTION: Ultrasonography and magnetic resonance imaging (MRI) are used to
evaluate shoulder disorders. This implementation study investigated outpatient
ultrasonography at an orthopedic practice in a managed care setting. METHODS: A
portable ultrasound machine was introduced at an orthopedic clinic in a group
practice. An orthopedic surgeon who primarily treated shoulder disorders received
15 hours of training. The impact of physician-performed ultrasonography on
subsequent MRI and other outcomes of patients with shoulder disorders from
January 2011 through October 2011 was determined using automated administrative
and clinical data. Comparisons were made to patients who did not undergo
ultrasonography at the experimental practice and 2 orthopedic clinics in the same
practice. RESULTS: During the study, 146 ultrasound examinations were
administered. Compared with patients who did not undergo ultrasonography,
patients who received ultrasonography had significantly higher comorbidity.
However, they were significantly less likely to have MRI (9.7% with
ultrasonography vs 14.4% without; p = 0.03) although equally likely to undergo
surgery (33.6% with ultrasonography vs 22.1% without, p = 0.77). Mean time to
surgery was 89.3 +/- 49.3 days for patients with ultrasonography vs 32.9 +/- 43.3
days for patients without (p < 0.05). No ultrasonography-examined patients had an
incorrect diagnosis at surgery. For patients receiving ultrasonography, an
estimated 35 MRIs were avoided, saving a predicted $17,603, a 50% return in less
than 1 year on a $34,897 investment for an ultrasound machine and supplies.
CONCLUSION: Outpatient ultrasonography by an orthopedic surgeon can be useful for
diagnosing shoulder disorders and might reduce MRI utilization.
PMID- 24355887
TI - Nonbeneficial treatment and conflict resolution: building consensus.
AB - INTRODUCTION: We established a fair and explicit nonbeneficial treatment and
conflict resolution policy at our medical center. The policy was designed to help
us acknowledge and respect both patients and clinicians involved in treatment
planning and decision making. OBJECTIVE: To qualitatively describe how our
hospitalwide nonbeneficial treatment and conflict resolution policy was used.
DESIGN: Retrospective evaluation of all bioethics consultations from November 6,
2009, when the policy was adopted, through August 6, 2012. Case-specific data
were obtained when nonconsensus occurred involving withholding or withdrawing of
nonbeneficial treatment. MAIN OUTCOME MEASURES: Rates of resolution of conflicts
and treatment plan consensus when nonbeneficial treatment was withheld or
withdrawn. RESULTS: We identified 146 (39.4%) cases where there was a treatment
level conflict between patients/surrogates and the treatment teams responsible
for their care. In 54 (37.0%) of the cases, resolution occurred. In 92 (63.0%) of
the cases, nonbeneficial treatment was eventually withheld or withdrawn. In 87
(94.6%) of the cases where treatment was withheld or withdrawn, the treatment
teams and patients/surrogates reached consensus by the conclusion of the
bioethics consultation process using the fair and explicit nonbeneficial
treatment and conflict resolution policy. CONCLUSION: A fair and explicit
nonbeneficial treatment and conflict resolution policy can result in a high level
of consensus between patients/surrogates and the treatment teams responsible for
their care when treatment is withheld or withdrawn.
PMID- 24355888
TI - Ambulatory treatment gaps in patients with ischemic stroke or transient ischemic
attack.
AB - BACKGROUND: This study evaluated goal attainment for patients with a history of
non-cardioembolic ischemic stroke (NCIS) or transient ischemic attack (TIA).
METHODS: A cross-sectional study was conducted in patients aged 18 to 85 years
with a history of validated NCIS or TIA. Data collected were demographics,
comorbidities, blood pressure (BP), low-density lipoprotein cholesterol (LDL-C)
values, and medications within 365 days and most proximal to December 31, 2010.
Goal LDL-C and BP were defined as < 100 mg/dL and < 140/90 mm Hg, respectively.
Differences in sex and age (< 65 vs >= 65 years) were evaluated. RESULTS: There
were 1731 patients evaluated (mean age: 73.6 years; 58% women). Stroke type was
NCIS in 51.9% and TIA in 48.1%. The LDL-C and BP were measured in 75.4% and 50.3%
of patients, respectively. No difference in LDL-C screening rates existed for sex
or age. Men and patients younger than age 65 years were significantly more likely
to have BP measured. Overall, LDL-C and BP goals were attained by 48.9% and 43.3%
of patients, respectively. Men and patients age 65 years or older were likelier
than women and patients younger than age 65 years to attain LDL-C goals (p <
0.01). Men were also likelier than women to attain BP < 140/90 mm Hg (p < 0.01),
but more patients younger than age 65 years vs older than age 65 years attained
this goal (p < 0.01). Statins and antihypertensives were received by 51.9% and
46.9% of the patients, respectively. CONCLUSION: Although attaining guideline
recommended goals for LDL-C and BP may present challenges, future research should
focus on innovative methods to help patients attain optimal treatment goals.
PMID- 24355889
TI - Identification of internal and external stressors in parents of newborns in
intensive care.
AB - The purpose of this study was to identify parents' self-reported stressors as
they experience their baby's course in the neonatal intensive care unit (NICU).
Miles, Funk & Carlson (1993) Parental Stressor Scale: Neonatal Intensive Care
Unit was used to survey 119 parents of neonatal infants, born at 24 weeks to full
term, in the 28-bed level 3 NICU of a mid-Atlantic, Magnet-designated acute care
hospital with 665 licensed beds. The newly developed Grosik, Snyder, Cleary and
Tidwell NICU External Stressors and Stress Reduction Scale (2006), a 5-point
Likert scale, was also used. Intrapersonal and interpersonal stressors were
categorized as internal (occurring within the NICU) and extrapersonal (occurring
outside the NICU) as external stressors. The findings were used to develop a new
practice in the NICU to help reduce parental stressors.
PMID- 24355890
TI - Acute uterine bleeding unrelated to pregnancy: a Southern California Permanente
Medical Group practice guideline.
AB - Acute uterine bleeding unrelated to pregnancy has been defined as bleeding
"sufficient in volume as to, in the opinion of the treating clinician, require
urgent or emergent intervention." The Southern California Permanente Medical
Group updated its guidelines for the management of this condition on the basis of
the best available evidence, as identified in a systematic review of the
available literature. Given the paucity of studies evaluating this condition, the
guidelines, by necessity, include recommendations largely based on opinion or
other sources such as case series that are, in general, categorized as low
quality evidence. Medical interventions with single or combined gonadal steroidal
agents administered parenterally or orally show promise, but more high-quality
studies are needed to better define the appropriate drugs, dose, and
administrative scheduling. There is also some evidence that intrauterine
tamponade may be useful in at least selected cases. Special attention must be
paid to both diagnosing and treating inherited disorders of hemostasis, such as
von Willebrand disease, that may otherwise be underdiagnosed in both adolescent
and adult women.
PMID- 24355891
TI - The readmission reduction program of Kaiser Permanente Southern California
knowledge transfer and performance improvement.
AB - In 2011, Kaiser Permanente Northwest Region (KPNW) won the Lawrence Patient
Safety Award for its innovative work in reducing hospital readmission rates. In
2012, Kaiser Permanente Southern California (KPSC) won the Transfer Projects
Lawrence Safety Award for the successful implementation of the KPNW Region's
"transitional care" bundle to a Region that was almost 8 times the size of KPNW.
The KPSC Transition in Care Program consists of 6 KPNW bundle elements and 2
additional bundle elements added by the KPSC team. The 6 KPNW bundle elements
were risk stratification, standardized discharge summary, medication
reconciliation, a postdischarge phone call, timely follow-up with a primary care
physician, and a special transition phone number on discharge instructions. The 2
additional bundle elements added by KPSC were palliative care consult if
indicated and a complex-case conference. KPSC has implemented most of the KPNW
and KPSC bundle elements during the first quarter of 2012 for our Medicare risk
population at all of our 13 medical centers. Each year, KPSC discharges
approximately 40,000 Medicare risk patients. After implementation of bundle
elements, KPSC Medicare risk all-cause 30-day Healthcare Effectiveness Data and
Information Set readmissions observed-over-expected ratio and readmission rates
from December 2010 to November 2012 decreased from approximately 1.0 to 0.80 and
12.8% to 11%, respectively.
PMID- 24355892
TI - Current management of fecal incontinence.
AB - OBJECTIVE: To review the management of fecal incontinence, which affects more
than 1 in 10 people and can have a substantial negative impact on quality of
life. METHODS: The medical literature between 1980 and April 2012 was reviewed
for the evaluation and management of fecal incontinence. RESULTS: A comprehensive
history and physical examination are required to help understand the severity and
type of symptoms and the cause of incontinence. Treatment options range from
medical therapy and minimally invasive interventions to more invasive procedures
with varying degrees of morbidity. The treatment approach must be tailored to
each patient. Many patients can have substantial improvement in symptoms with
dietary management and biofeedback therapy. For younger patients with large
sphincter defects, sphincter repair can be helpful. For patients in whom
biofeedback has failed, other options include injectable medications,
radiofrequency ablation, or sacral nerve stimulation. Patients with
postdefecation fecal incontinence and a rectocele can benefit from rectocele
repair. An artificial bowel sphincter is reserved for patients with more severe
fecal incontinence. CONCLUSION: The treatment algorithm for fecal incontinence
will continue to evolve as additional data become available on newer
technologies.
PMID- 24355893
TI - Preventing type 2 diabetes mellitus: a call for personalized intervention.
AB - In parallel with the rising prevalence of obesity worldwide, especially in
younger people, there has been a dramatic increase in recent decades in the
incidence and prevalence of metabolic consequences of obesity, in particular
prediabetes and type 2 diabetes mellitus (DM2). Although approximately one-third
of US adults now meet one or more diagnostic criteria for prediabetes, only a
minority of those so identified as being at risk for DM2 actually progress to
diabetes, and some may regress to normal status. Given the uncertain prognosis of
prediabetes, it is not clear who is most likely to benefit from lifestyle change
or medication interventions that are known to reduce DM2 risk. We review the many
factors known to influence risk of developing DM2 and summarize treatment trials
demonstrating the possibility of preventing DM2. Applying the concepts of
personalized medicine and the potential of "big data" approaches to analysis of
massive amounts of routinely gathered clinical and laboratory data from large
populations, we call for the development of tools to more precisely estimate
individual risk of DM2.
PMID- 24355894
TI - Telepsychiatry in correctional facilities: using technology to improve access and
decrease costs of mental health care in underserved populations.
AB - OBJECTIVE: It is unclear if telepsychiatry, a subset of telemedicine, increases
access to mental health care for inmates in correctional facilities or decreases
costs for clinicians or facility administrators. The purpose of this
investigation was to determine how utilization of telepsychiatry affected access
to care and costs of providing mental health care in correctional facilities.
METHODS: A literature review complemented by a semistructured interview with a
telepsychiatry practitioner. Five electronic databases, the National Bureau of
Justice, and the American Psychiatric Association Web sites were searched for
this research, and 49 sources were referenced. The literature review examined
implementation of telepsychiatry in correctional facilities in Arizona,
California, Georgia, Kansas, Ohio, Texas, and West Virginia to determine the
effect of telepsychiatry on inmate access to mental health services and the costs
of providing mental health care in correctional facilities. RESULTS:
Telepsychiatry provided improved access to mental health services for inmates,
and this increase in access is through the continuum of mental health care, which
has been instrumental in increasing quality of care for inmates. Use of
telepsychiatry saved correctional facilities from $12,000 to more than $1
million. The semistructured interview with the telepsychiatry practitioner
supported utilization of telepsychiatry to increase access and lower costs of
providing mental health care in correctional facilities. CONCLUSIONS: Increasing
access to mental health care for this underserved group through telepsychiatry
may improve living conditions and safety inside correctional facilities.
Providers, facilities, and state and federal governments can expect increased
savings with utilization of telepsychiatry.
PMID- 24355896
TI - Simple rules that reduce hospital readmission.
AB - To overcome system failures, health care organizations must implement a few
simple rules of complex adaptive systems. I describe Transition in Care, Kaiser
Permanente Southern California's program to reduce hospital readmissions, as an
example of a program design that meets the principles of complex adaptive systems
and enumerate five rules, which must be followed if a health system is to create
value for their stakeholders.
PMID- 24355895
TI - What does professionalism mean to the physician?
AB - Professionalism, which is a core competency for physicians, can be described as a
spectrum of behaviors and may have a significant impact on the problems in
today's changing health care climate. In this article, we discuss the meaning of
professionalism and its role in the Southern California Permanente Medical Group
(SCPMG) and consider how it may be applied to integrated care delivery systems
such as Kaiser Permanente. To understand professionalism, one must consider
Stern's definition, which consists of four principles: excellence, humanism,
accountability, and altruism. SCPMG has taken three of these principles
excellence, accountability, and altruism-and divided the fourth, humanism, into
another three principles similar to those identified by the University of
California Los Angeles Task Force on Professionalism: humanitarianism, respect
for others, and honor and integrity. SCPMG has a rich history and culture of
promoting clinical excellence and professionalism, as evidenced by the programs
and initiatives described throughout this article. Indeed, the SCPMG experience
validates professionalism as a core physician competency comprising a set of
behaviors that are continually refined.
PMID- 24355897
TI - Death wish of a cardiac transplant patient.
PMID- 24355898
TI - Unraveling the devil in disguise: how I dodged a bullet and turned the worst
possible patient experience into the greatest achievement of my medical career.
PMID- 24355899
TI - Mixed cryoglobulinemia: an unusual presentation of hepatitis C.
AB - A 50-year-old man with a history of hepatitis C presented with recurrent episodes
of abdominal pain, arthralgia, and weakness. Although these symptoms seemed
rather non-specific, a purpuric rash of the lower extremities was the final clue
to diagnosis. The diagnosis was then confirmed by histopathologic and serologic
testing.
PMID- 24355900
TI - Infection control practice in the operating room: staff adherence to existing
policies in a developing country.
AB - CONTEXT: Infection control interventions are important for containing surgery
related infections. For this reason, the modern operating room (OR) should have
well-developed infection control policies. The efficacy of these policies depends
on how well the OR staff adhere to them. There is a lack of available data
documenting adherence to infection control policies. OBJECTIVE: To evaluate OR
staff adherence to existing infection control policies in Jamaica. METHODS: We
administered a questionnaire to all OR staff to assess their training, knowledge
of local infection control protocols, and practice with regard to 8 randomly
selected guidelines. Adherence to each guideline was rated with fixed-choice
items on a 4-point Likert scale. The sum of points determined the adherence
score. Two respondent groups were defined: adherent (score > 26) and nonadherent
(score <= 26). We evaluated the relationship between respondent group and age,
sex, occupational rank, and time since completion of basic medical training. We
used chi(2) and Fisher exact tests to assess associations and t tests to compare
means between variables of interest. RESULTS: The sample comprised 132
participants (90 physicians and 42 nurses) with a mean age of 36 (standard
deviation +/- 9.5) years. Overall, 40.1% were adherent to existing protocols.
There was no significant association between the distribution of adherence scores
and sex (p = 0.319), time since completion of basic training (p = 0.595),
occupational rank (p = 0.461), or age (p = 0.949).Overall, 19% felt their
knowledge of infection control practices was inadequate. Those with working
knowledge of infection control practices attained it mostly through informal
communication (80.4%) and self-directed research (62.6%). CONCLUSION: New
approaches to the problem of nonadherence to infection control guidelines are
needed in the Caribbean. Several unique cultural, financial, and environmental
factors influence adherence in this region, in contrast to conditions in
developed countries.
PMID- 24355901
TI - Image diagnosis: a curious case of causeless clubbing.
PMID- 24355902
TI - Image diagnosis: headache and an isolated oculomotor nerve palsy.
PMID- 24355903
TI - Leadership in surgery for public sector hospitals in Jamaica: strategies for the
operating room.
AB - The barriers to health care delivery in developing nations are many:
underfunding, limited support services, scarce resources, suboptimal health care
worker attitudes, and deficient health care policies are some of the challenges.
The literature contains little information about health care leadership in
developing nations. This discursive paper examines the impact of leadership on
the delivery of operating room (OR) services in public sector hospitals in
Jamaica.Delivery of OR services in Jamaica is hindered by many unique cultural,
financial, political, and environmental barriers. We identify six leadership
goals adapted to this environment to achieve change. Effective leadership must
adapt to the environment. Delivery of OR services in Jamaica may be improved by
addressing leadership training, workplace safety, interpersonal communication,
and work environment and by revising existing policies. Additionally, there
should be regular practice audits and quality control surveys.
PMID- 24355904
TI - Reversal of acute complex regional pain syndrome using the practical application
of neurodiagnostic evaluation process: a case study.
AB - In 2005, a patient in my practice developed complex regional pain syndrome type 1
(CRPS 1) after bunion surgery. The condition was properly diagnosed within 4
weeks with a diagnostic technique that I routinely use to diagnose chronic
musculoskeletal pain, and it was successfully treated. The tests, which are based
on primitive and postural reflexes in infants, were adapted to reflect normal and
abnormal motor behaviors in adults after provocation of reflexes of the autonomic
nervous system (afferent C fibers in peripheral nerves). Approximately 60 days
after my patient's operation, the tests indicated a positive reflex at the
posterior tibial nerve in the operated foot. Surgery to remove an accessory
ossicle from the talus adjacent to this nerve resolved the CRPS 1 within 2 weeks.
Since CRPS 1 is a dysfunctional state of the autonomic regulatory control of
pain, it was postulated that a test based on autonomic nerve function could
isolate the source of CRPS 1. The Practical Application of Neurodiagnostic
Evaluation process was shown to be diagnostic for the cause of acute CRPS 1 and
to allow its reversal. Further evaluation of the test for diagnosis and treatment
of CRPS is needed.
PMID- 24355906
TI - Training patient and family storytellers and patient and family faculty.
AB - Narrative medicine has become a prominent method of developing more empathetic
relationships between medical clinicians and patients, on the basis of a deeper
understanding of the patient experience. Beyond its usefulness during clinical
encounters, patient storytelling can inform processes and procedures in Advisory
Councils, Committee Meetings, and Family as Faculty settings, leading to improved
quality and safety in health care. Armed with a better understanding of the
patient experience, clinicians and administrators can make decisions, hopefully
in collaboration with patients, that will enrich the patient experience and
increase satisfaction among patients, families, and staff. Patient and family
storytelling is a key component of the collaboration that is ideal when an
organization seeks to deliver patient- and family-centered care. Providing
patients and families with training will make the narratives they share more
powerful. Health care organizations will find that purposeful storytelling can be
an invaluable aspect of a patient- and family-centered culture. Well-delivered
storytelling will support quality- and safety-improvement efforts and contribute
to improved patient satisfaction. This article provides instruction for teaching
patients and families how to tell stories with purpose and offers advice about
how to support patients, families, and clinicians participating in this effort.
PMID- 24355905
TI - Adverse childhood experiences and psychosocial well-being of women who were in
foster care as children.
AB - BACKGROUND AND OBJECTIVE: Research has shown that many children in foster care
later have psychosocial problems as adults; this is often attributed to
cumulative adversities and a lack of supportive caregivers. The risk factors
associated with foster care, such as maternal separation and multiple placements,
often counteract many protective factors that can ameliorate the effects of
childhood adversities. This study assessed the relationship between adverse
childhood experiences (ACEs) and psychosocial well-being in women who were in
foster care as children. METHODS: A total of 101 women aged 18-71 years (mean,
36.83 [12.95] years) completed an anonymous online survey based on the 10-item
ACE Questionnaire, the Sense of Coherence questionnaire, and the General Health
Questionnaire. RESULTS: More than 56% of respondents were identified as
experiencing current psychological distress. Sense of coherence scores (mean,
54.26 [15.35]) showed a significant inverse association with both General Health
Questionnaire (mean, 14.83 [5.88]) and ACE (mean, 5.68 [2.90]) scores (r = -0.64
and -0.31, respectively) and 97% reported at least 1 ACE, 70% reported >= 5 and
33% reported >= 8. Linear regressions indicated that ACEs reported to occur
before foster care were associated with lower levels of sense of coherence (8%)
and higher levels of psychological distress (6%). Physical neglect and living in
a dysfunctional household (parental loss, maternal abuse, or household member
associated with substance abuse or prison) significantly decreased during foster
care by 16 and 19 percentage points, respectively. Rates of emotional and
physical abuse did not change. CONCLUSION: The number of ACEs was associated with
the level of psychological distress. Our findings suggest that children entering
the foster care system are already vulnerable and at risk of experiencing ACEs
during foster care and psychological distress during adulthood. Measures
implemented to protect children must not cause more harm than good. Social
services that preserve and strengthen the family unit and reduce the number of
ACEs both before and during foster care are recommended. Social workers and
clinicians who are trained to address and manage the unique developmental needs
of children in foster care may help reduce the effects of ACEs and optimize
developmental health.
PMID- 24355907
TI - Reported consumption of takeaway food and its contribution to socioeconomic
inequalities in body mass index.
AB - The aim of this study was to examine whether takeaway food consumption mediated
(explained) the association between socioeconomic position and body mass index
(BMI). A postal-survey was conducted among 1500 randomly selected adults aged
between 25 and 64years in Brisbane, Australia during 2009 (response rate 63.7%,
N=903). BMI was calculated using self-reported weight and height. Participants
reported usual takeaway food consumption, and these takeaway items were
categorised into "healthy" and "less healthy" choices. Socioeconomic position was
ascertained by education, household income, and occupation. The mean BMI was
27.1kg/m(2) for men and 25.7kg/m(2) for women. Among men, none of the
socioeconomic measures were associated with BMI. In contrast, women with
diploma/vocational education (beta=2.12) and high school only (beta=2.60), and
those who were white-collar (beta=1.55) and blue-collar employees (beta=2.83) had
significantly greater BMI compared with their more advantaged counterparts.
However, household income was not associated with BMI. Among women, the
consumption of "less healthy" takeaway food mediated BMI differences between the
least and most educated, and between those employed in blue collar occupations
and their higher status counterparts. Decreasing the consumption of "less
healthy" takeaway options may reduce socioeconomic inequalities in overweight and
obesity among women but not men.
PMID- 24355908
TI - Product reformulation in the food system to improve food safety. Evaluation of
policy interventions.
AB - The objective of this study is to understand the level of attention that the
consumer awards to a balanced diet and to product ingredients, with a twofold
purpose: to understand whether food product reformulation can generate a
competitive advantage for companies that practice it and to evaluate the most
appropriate policy interventions to promote a healthy diet. Reformulation
strategy, in the absence of binding rules, could be generated by consumers.
Results from qualitative research and from empirical analysis have shown that the
question of health is a latent demand influenced by two main factors: a general
lack of information, and the marketing strategies adopted by companies which
bring about an increase in the information asymmetry between producers and
consumers. In the absence of binding rules, it is therefore necessary that the
government implement information campaigns (food education) aimed at increasing
knowledge regarding the effects of unhealthy ingredients, in order to inform and
improve consumer choice. It is only by means of widespread information campaigns
that food product reformulation can become a strategic variable and allow
companies to gain a competitive advantage. This may lead to virtuous results in
terms of reducing the social costs related to an unhealthy diet.
PMID- 24355909
TI - The role of sphingomyelin and sphingomyelin synthases in cell death,
proliferation and migration-from cell and animal models to human disorders.
AB - Sphingomyelin constitutes membrane microdomains such as lipid raft, caveolae, and
clathrin-coated pits and implicates in the regulation of trans-membrane
signaling. On the other hand, sphingomyelin emerges as an important molecule to
generate bioactive sphingolipids through ceramide. Sphingomyelin synthase is an
enzyme that generates sphingomyelin and diacylglycerol from phosphatidylcholine
and ceramide. Although ceramide has a well-known role as a lipid mediator to
regulate cell death and survival, the only known biological role of sphingomyelin
regulated by sphingomyelin synthases was limited to being a source of bioactive
lipids. Here, we describe the basic characters of sphingomyelin synthases and
discuss additional roles for sphingomyelin and sphingomyelin synthase in
biological functions including cell migration, apoptosis, autophagy, and cell
survival/proliferation as well as in human disorders such as cancer and
cardiovascular disorders. It is expected that a better understanding of the role
of sphingomyelin regulated by sphingomyelin synthase will shed light on new
mechanisms in cell biology, physiology and pathology. In the future, novel
therapeutic procedures for currently incurable diseases could be developed
through modifying the function of not only sphingolipids, such as sphingomyelin
and ceramide, but also of their regulatory enzymes. This article is part of a
Special Issue entitled New Frontiers in Sphingolipid Biology.
PMID- 24355910
TI - Answer to the letter to the editor by N. Sethi Eur Neurol, DOI:
10.1159/000356342.
PMID- 24355911
TI - Bolus-dependent dosimetric effect of positioning errors for tangential scalp
radiotherapy with helical tomotherapy.
AB - The dosimetric effect of errors in patient position is studied on-phantom as a
function of simulated bolus thickness to assess the need for bolus utilization in
scalp radiotherapy with tomotherapy. A treatment plan is generated on a
cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing
primarily tangential beamlets. A planning target volume with embedded scalplike
clinical target volumes (CTVs) is planned to a uniform dose of 200cGy.
Translational errors in phantom position are introduced in 1-mm increments and
dose is recomputed from the original sinogram. For each error the maximum dose,
minimum dose, clinical target dose homogeneity index (HI), and dose-volume
histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10mm.
Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range,
increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0
to 2mm of bolus is used. Utilizing 5mm of bolus resulted in a maximum HI value of
9.5 for the largest positioning errors. Using 0 to 2mm of bolus resulted in
minimum and maximum dose values of 85% to 94% and 118% to 125% of the
prescription dose, respectively. When using 5mm of bolus these values were 98.5%
and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5mm of
bolus, even for the largest positioning errors. CTV dose homogeneity becomes
increasingly sensitive to errors in patient position as bolus thickness decreases
when treating the scalp with primarily tangential beamlets. Performing a radial
expansion of the scalp CTV into 5mm of bolus material minimizes dosimetric
sensitivity to errors in patient position as large as 5mm and is therefore
recommended.
PMID- 24355912
TI - Congenital dermal sinus with an infected dermoid cyst in the cervico-thoracic
spinal cord.
AB - Congenital dermal sinuses (CDS) are epithelium-lined tracts that result from
incomplete separation of cutaneous ectoderm from the underlying neuroectoderm.
CDS may be associated with dermoid cysts and can cause complications by mass
effect and by functioning as a pathway for infection. Cervical and thoracic
tracts are rare, making up 1 and 10% of all CDS, respectively. We present an
unusual case of a cervico-thoracic CDS with concomitant infected dermoid leading
to neurological dysfunction. A 1-year-old male with a normal developmental
history presented with a several-week history of progressive weakness. Previous
visits to two outside emergency departments diagnosed the patient with acute
otitis media. After another episode of fever and worsening of neurological
symptoms, the patient was correctly diagnosed as having CDS with an infected
dermoid cyst. Antibiotics were initiated, the lesion was resected, and the
patient improved neurologically. Although cervical and thoracic CDS with infected
dermoids are rare, one should have a high index of suspicion when cutaneous
stigmata of spinal dysraphism are identified. Due to the risk of neurological
deterioration, the recommended treatment of CDS with or without a concomitant
intraspinal dermoid is prompt administration of antibiotics and definitive
surgical intervention.
PMID- 24355913
TI - Acute stroke thrombolysis in end-stage renal disease: a national survey of
nephrologist opinion.
AB - BACKGROUND/AIMS: Systemic thrombolysis for acute ischaemic stroke is the standard
of care in the UK. In the absence of trial data on the safety and efficacy of
this treatment in patients with end-stage renal disease, we captured the views of
UK nephrologists to highlight health care policy and research objectives.
METHODS: Consultant nephrologists participated in an internet-based
questionnaire. Respondents were asked about their involvement in thrombolysis
decisions, safety concerns in dialysis patients, views on stroke rehabilitation
and opinions on antiplatelet and warfarin use for stroke prevention. RESULTS:
122/433 (28%) clinicians responded. 75% wanted involvement in thrombolysis
decisions although just 10% gave input in practice. 64% expressed a high degree
of concern (>=7/10) regarding intracranial bleeding risk in haemodialysis (HD).
Overall risks of intra- and extracranial bleeding were rated lower in peritoneal
dialysis (PD; p < 0.001). 85% felt the HD schedule impacted negatively on
rehabilitation, whereas 63% felt this was the case in the context of PD (p =
0.001). More clinicians favoured warfarin for stroke prevention in PD patients
with atrial fibrillation in comparison with HD patients (79 vs. 66%, p = 0.04).
CONCLUSION: The majority of nephrologists want involvement in thrombolysis
decisions relevant to their patients. Concerns about bleeding risks with
thrombolysis are high and we identify a vital need to improve access to stroke
rehabilitation in the UK, especially in HD patients.
PMID- 24355914
TI - More than skin deep: connecting melanocyte pigmentation and angiogenic diseases.
AB - Epidemiological studies have identified racial differences in susceptibility to
numerous diseases, including several ocular and skin diseases characterized by
increased vascular growth. In most cases, the specific mechanisms and genetic
variants responsible for these differences have remained elusive. In this issue
of the JCI, Adini et al. explore a direct connection between skin pigmentation
and susceptibility to angiogenic diseases and identify an extracellular matrix
protein that is regulated by melanogenesis and potently modulates angiogenesis.
PMID- 24355915
TI - Toward postnatal reversal of ocular congenital malformations.
AB - Aniridia is a panocular disorder that severely affects vision in early life. Most
cases are caused by dominantly inherited mutations or deletions of the PAX6 gene,
which encodes a transcription factor that is essential for the development of the
eye and the central nervous system. In this issue of the JCI, Gregory-Evans and
colleagues demonstrate that early postnatal topical administration of an ataluren
based formulation reverses congenital malformations in the postnatal mouse eye,
providing evidence that manipulation of PAX6 after birth may lead to corrective
tissue remodeling. These findings offer hope that ataluren administration could
be a therapeutic paradigm applicable to some major congenital eye defects.
PMID- 24355916
TI - Hostile takeover: fungal protein promotes host cell invasion.
AB - The ability to suppress the immune system has lead to great advances in
transplant technology and treatment of autoimmune diseases. Unfortunately, the
immunosuppression of these patients has led to the rise of opportunistic
infections by organisms that are recalcitrant to current prophylactic strategies.
One such example is the increase of mucormycosis, an invasive infection caused by
filamentous fungi of the order Mucorales. In this issue of the JCI, Gebremariam
and colleagues determined that spore coat homolog (CotH) proteins are required
for angioinvasion and that these proteins are unique to Mucorales. Their findings
provide a potential therapeutic target for prevention and treatment of
mucormycosis.
PMID- 24355917
TI - Aortic aneurysms in Loeys-Dietz syndrome - a tale of two pathways?
AB - Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized
by skeletal abnormalities, craniofacial malformations, and a high predisposition
for aortic aneurysm. In this issue of the JCI, Gallo et al. developed transgenic
mouse strains harboring missense mutations in the genes encoding type I or II TGF
beta receptors. These mice exhibited several LDS-associated phenotypes. Despite
being functionally defective, the mutated receptors enhanced TGF-beta signaling
in vivo, inferred by detection of increased levels of phosphorylated Smad2.
Aortic aneurysms in these LDS mice were ablated by treatment with the Ang II type
1 (AT1) receptor antagonist losartan. The results from this study will foster
further interest into the potential therapeutic implications of AT1 receptor
antagonists.
PMID- 24355918
TI - The search for treatments to reduce chemotherapy-induced peripheral neuropathy.
AB - Oxaliplatin, a commonly used chemotherapeutic agent, is associated with both
acute and chronic neurotoxicity. Chronic sensory neuropathy can be dose limiting
and may have detrimental effects on patients' quality of life. Preclinical
studies provide an understanding of the pathophysiology of chemotherapy-induced
peripheral neuropathy (CIPN) and may be important for developing effective
preventative interventions. In this issue of the JCI, Coriat and colleagues used
an animal model and a human pilot trial to evaluate the use of mangafodipir to
reduce CIPN. Although many pilot clinical studies have reported promising data,
larger clinical trials have repeatedly been unable to confirm these preliminary
results. Thus, no agents are currently clinically recommended for the prevention
of CIPN.
PMID- 24355919
TI - Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver
disease in mice.
AB - Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results from
mutations in the alpha-1 antitrypsin (AAT) gene. The mutant AAT protein
aggregates and accumulates in the liver leading to AATD liver disease, which is
only treatable by liver transplant. The PiZ transgenic mouse strain expresses a
human AAT (hAAT) transgene that contains the AATD-associated Glu342Lys mutation.
PiZ mice exhibit many AATD symptoms, including AAT protein aggregates, increased
hepatocyte death, and liver fibrosis. In the present study, we systemically
treated PiZ mice with an antisense oligonucleotide targeted against hAAT (AAT
ASO) and found reductions in circulating levels of AAT and both soluble and
aggregated AAT protein in the liver. Furthermore, AAT-ASO administration in these
animals stopped liver disease progression after short-term treatment, reversed
liver disease after long-term treatment, and prevented liver disease in young
animals. Additionally, antisense oligonucleotide treatment markedly decreased
liver fibrosis in this mouse model. Administration of AAT-ASO in nonhuman
primates led to an approximately 80% reduction in levels of circulating normal
AAT, demonstrating potential for this approach in higher species. Antisense
oligonucleotides thus represent a promising therapy for AATD liver disease.
PMID- 24355920
TI - Treatment of oxaliplatin-induced peripheral neuropathy by intravenous
mangafodipir.
AB - BACKGROUND: The majority of patients receiving the platinum-based chemotherapy
drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity
involves ROS production, we investigated the efficacy of mangafodipir, a molecule
that has antioxidant properties and is approved for use as an MRI contrast
enhancer. METHODS: The effects of mangafodipir were examined in mice following
treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced
oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23
cancer patients with grade >= 2 oxaliplatin-induced neuropathy in a phase II
study, with 22 patients receiving i.v. mangafodipir following oxaliplatin.
Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and
mangafodipir. RESULTS: Mangafodipir prevented motor and sensory dysfunction and
demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of
mangafodipir treatment. In 77% of patients treated with oxaliplatin and
mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles,
neurotoxicity was downgraded to grade >= 2 in 6 of 7 patients. Prior to
enrollment, patients received an average of 880 +/- 239 mg/m2 oxaliplatin.
Patients treated with mangafodipir tolerated an additional dose of 458 +/- 207
mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed
a cumulative dose of 1,426 +/- 204 mg/m2 oxaliplatin. Serum AOPPs were lower in
responders compared with those in nonresponders. CONCLUSION: Our study suggests
that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in
cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding.
Universite Paris Descartes, Ministere de la Recherche et de l'Enseignement
Superieur, and Assistance Publique-Hopitaux de Paris.
PMID- 24355921
TI - Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin
receptor sorting.
AB - Defective neurogenesis in the postnatal brain can lead to many neurological and
psychiatric disorders, yet the mechanism behind postnatal neurogenesis remains to
be investigated. Huntingtin-associated protein 1 (HAP1) participates in
intracellular trafficking in neurons, and its absence leads to postnatal death in
mice. Here, we used tamoxifen-induced (TM-induced) Cre recombination to deplete
HAP1 in mice at different ages. We found that HAP1 reduction selectively affects
survival and growth of postnatal mice, but not adults. Neurogenesis, but not
gliogenesis, was affected in HAP1-null neurospheres and mouse brain. In the
absence of HAP1, postnatal hypothalamic neurons exhibited reduced receptor
tropomyosin-related kinase B (TRKB) levels and decreased survival. HAP1
stabilized the association of TRKB with the intracellular sorting protein
sortilin, prevented TRKB degradation, and promoted its anterograde transport. Our
findings indicate that intracellular sorting of neurotrophin receptors is
critical for postnatal neurogenesis and could provide a therapeutic target for
defective postnatal neurogenesis.
PMID- 24355922
TI - Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
AB - Studies have established that pigmentation can provide strong, protective effects
against certain human diseases. For example, angiogenesis-dependent diseases such
as wet age-related macular degeneration and infantile hemangioma are more common
in light-skinned individuals of mixed European descent than in African-Americans.
Here we found that melanocytes from light-skinned humans and albino mice secrete
high levels of fibromodulin (FMOD), which we determined to be a potent angiogenic
factor. FMOD treatment stimulated angiogenesis in numerous in vivo systems,
including laser-induced choroidal neovascularization, growth factor-induced
corneal neovascularization, wound healing, and Matrigel plug assays.
Additionally, FMOD enhanced vascular sprouting during normal retinal development.
Deletion of Fmod in albino mice resulted in a marked reduction in the amount of
neovascularization induced by retinal vein occlusion, corneal growth factor
pellets, and Matrigel plugs. Our data implicate the melanocyte-secreted factor
FMOD as a key regulator of angiogenesis and suggest an underlying mechanism for
epidemiological differences between light-skinned individuals of mixed European
descent and African-Americans. Furthermore, inhibition of FMOD in humans has
potential as a therapeutic strategy for treating angiogenesis-dependent diseases.
PMID- 24355923
TI - Angiotensin II-dependent TGF-beta signaling contributes to Loeys-Dietz syndrome
vascular pathogenesis.
AB - Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized
by a high risk for aneurysm and dissection throughout the arterial tree and
phenotypically resembles Marfan syndrome. LDS is caused by heterozygous missense
mutations in either TGF-beta receptor gene (TGFBR1 or TGFBR2), which are
predicted to result in diminished TGF-beta signaling; however, aortic surgical
samples from patients show evidence of paradoxically increased TGF-beta
signaling. We generated 2 knockin mouse strains with LDS mutations in either
Tgfbr1 or Tgfbr2 and a transgenic mouse overexpressing mutant Tgfbr2. Knockin and
transgenic mice, but not haploinsufficient animals, recapitulated the LDS
phenotype. While heterozygous mutant cells had diminished signaling in response
to exogenous TGF-beta in vitro, they maintained normal levels of Smad2
phosphorylation under steady-state culture conditions, suggesting a chronic
compensation. Analysis of TGF-beta signaling in the aortic wall in vivo revealed
progressive upregulation of Smad2 phosphorylation and TGF-beta target gene
output, which paralleled worsening of aneurysm pathology and coincided with
upregulation of TGF-beta1 ligand expression. Importantly, suppression of Smad2
phosphorylation and TGF-beta1 expression correlated with the therapeutic efficacy
of the angiotensin II type 1 receptor antagonist losartan. Together, these data
suggest that increased TGF-beta signaling contributes to postnatal aneurysm
progression in LDS.
PMID- 24355924
TI - Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation
defects.
AB - Aniridia is a congenital and progressive panocular condition with poor visual
prognosis that is associated with brain, olfactory, and pancreatic abnormalities.
Development of aniridia is linked with nonsense mutations that result in paired
box 6 (PAX6) haploinsufficiency. Here, we used a mouse model of aniridia to test
the hypothesis that manipulation of Pax6 dosage through a mutation-independent
nonsense mutation suppression strategy would limit progressive, postnatal damage
in the eye. We focused on the nonsense suppression drugs 3-[5-(2-fluorophenyl)
1,2,4-oxadiazol-3-yl]benzoic acid (ataluren) and gentamicin. Remarkably, we
demonstrated that nonsense suppression not only inhibited disease progression but
also stably reversed corneal, lens, and retinal malformation defects and restored
electrical and behavioral responses of the retina. The most successful results
were achieved through topical application of the drug formulation START (0.9%
sodium chloride, 1% Tween 80, 1% powdered ataluren, 1% carboxymethylcellulose),
which was designed to enhance particle dispersion and to increase suspension
viscosity. These observations suggest that the eye retains marked developmental
plasticity into the postnatal period and remains sensitive to molecular
remodeling. Furthermore, these data indicate that other neurological
developmental anomalies associated with dosage-sensitive genetic mutations may be
reversible through nonsense suppression therapeutics.
PMID- 24355926
TI - CotH3 mediates fungal invasion of host cells during mucormycosis.
AB - Angioinvasion is a hallmark of mucormycosis. Previously, we identified
endothelial cell glucose-regulated protein 78 (GRP78) as a receptor for Mucorales
that mediates host cell invasion. Here we determined that spore coat protein
homologs (CotH) of Mucorales act as fungal ligands for GRP78. CotH proteins were
widely present in Mucorales and absent from noninvasive pathogens. Heterologous
expression of CotH3 and CotH2 in Saccharomyces cerevisiae conferred the ability
to invade host cells via binding to GRP78. Homology modeling and computational
docking studies indicated structurally compatible interactions between GRP78 and
both CotH3 and CotH2. A mutant of Rhizopus oryzae, the most common cause of
mucormycosis, with reduced CotH expression was impaired for invading and damaging
endothelial cells and CHO cells overexpressing GRP78. This strain also exhibited
reduced virulence in a diabetic ketoacidotic (DKA) mouse model of mucormycosis.
Treatment with anti-CotH Abs abolished the ability of R. oryzae to invade host
cells and protected DKA mice from mucormycosis. The presence of CotH in Mucorales
explained the specific susceptibility of DKA patients, who have increased GRP78
levels, to mucormycosis. Together, these data indicate that CotH3 and CotH2
function as invasins that interact with host cell GRP78 to mediate pathogenic
host-cell interactions and identify CotH as a promising therapeutic target for
mucormycosis.
PMID- 24355925
TI - Heparan sulfate deficiency disrupts developmental angiogenesis and causes
congenital diaphragmatic hernia.
AB - Congenital diaphragmatic hernia (CDH) is a common birth malformation with a
heterogeneous etiology. In this study, we report that ablation of the heparan
sulfate biosynthetic enzyme NDST1 in murine endothelium (Ndst1ECKO mice)
disrupted vascular development in the diaphragm, which led to hypoxia as well as
subsequent diaphragm hypoplasia and CDH. Intriguingly, the phenotypes displayed
in Ndst1ECKO mice resembled the developmental defects observed in slit homolog 3
(Slit3) knockout mice. Furthermore, introduction of a heterozygous mutation in
roundabout homolog 4 (Robo4), the gene encoding the cognate receptor of SLIT3,
aggravated the defect in vascular development in the diaphragm and CDH. NDST1
deficiency diminished SLIT3, but not ROBO4, binding to endothelial heparan
sulfate and attenuated EC migration and in vivo neovascularization normally
elicited by SLIT3-ROBO4 signaling. Together, these data suggest that heparan
sulfate presentation of SLIT3 to ROBO4 facilitates initiation of this signaling
cascade. Thus, our results demonstrate that loss of NDST1 causes defective
diaphragm vascular development and CDH and that heparan sulfate facilitates
angiogenic SLIT3-ROBO4 signaling during vascular development.
PMID- 24355927
TI - Misalignment of a novel single-piece acrylic intraocular lens in the first three
months after surgery.
AB - PURPOSE: To evaluate the misalignment of a new single-piece microincisional
hydrophobic acrylic intraocular lens (IOL) in emmetropic, myopic and hyperopic
eyes within the first 3 months after surgery. SETTING: Vienna Institute for
Research in Ocular Surgery, Karl Landsteiner Institute, Hanusch Hospital,
Department of Ophthalmology, Vienna, Austria. METHODS: Patients with age-related
cataract were included in this prospective study. Each patient received a single
piece microincisional hydrophobic acrylic IOL (AF-1 NY-60, Hoya) in the study
eye. Subgroups of emmetropic, myopic and hyperopic eyes were defined according to
IOL power calculation. Anterior chamber depth (ACD) measurements were performed
with an AC-Master. Tilt and decentration of the IOL were measured with a Purkinje
meter. Follow-up assessments were performed 1 h, 3 weeks and 3 months after
surgery. RESULTS: Forty-two eyes of 42 patients (21 emmetropic, 10 myopic and 11
hyperopic eyes) were included. The mean ACD 1 h, 3 weeks and 3 months after
surgery was 4.597 +/- 0.533, 4.483 +/- 0.347 and 4.438 +/- 0.398 mm,
respectively. Differences in ACD between follow-ups and between subgroups were
not statistically significant (both p > 0.05). On average, 3 months after surgery
IOLs were tilted 0.81 +/- 2.86 degrees nasally and 0.70 +/- 3.13 degrees
inferiorly and decentered 0.06 +/- 0.24 mm nasally and 0.15 +/- 0.29 mm
superiorly. Differences in tilt and decentration were not statistically
significant (both p > 0.05). We observed 1 case of severe capsular fibrosis.
CONCLUSIONS: The single-piece microincisional hydrophobic acrylic IOL showed good
axial stability and only little, clinically not relevant tilt and decentration in
the first 3 months after surgery.
PMID- 24355928
TI - Walking habits and health-related factors in 75-year-old Iranian women and men.
AB - An active life style can postpone the aging process, prevent many aspects of
functional decline and improve health and quality of life. The aim of this study
was to compare elderly people who walked at least 30 min a day with others who
walked less, from a gender perspective, regarding perceived health and fitness,
physiological capacity and functional performance. A representative sample of 75
year-olds born 1932-33 and living in Tehran, in 2007-2008 was included by
randomly selecting 1100 subjects from the latest Iranian census records (1996) by
the Statistical Centre of Iran using computerized methods. Participants answered
questions regarding health status and physical activity and performed functional
tests. Better results for Walkers were observed in most subjective and objective
outcome measures. Walkers were less likely to feel generally tired, more likely
to have better physical fitness and to have the maximum score on the Falls
Efficacy Scale, less likely to feel unstable during walking outdoors and less
likely to be dependent or unsafe in ADL. Walkers of both genders performed better
in the following tests: chair stand, one leg stance, maximal walking speed and
six min walking. The difference between Walkers and Non-Walkers was greater in
men. In general, older women and men who walked at least 30 min daily/almost
daily showed better results in most health-related outcomes, ADL and functional
performance than people who walked less. This study showed gender differences in
the level of physical activity and functioning that must be taken into account
when planning intervention programs.
PMID- 24355929
TI - Manipulation of arthropod sex determination by endosymbionts: diversity and
molecular mechanisms.
AB - Arthropods exhibit a large variety of sex determination systems both at the
chromosomal and molecular level. Male heterogamety, female heterogamety, and
haplodiploidy occur frequently, but partially different genes are involved.
Endosymbionts, such as Wolbachia, Cardinium,Rickettsia, and Spiroplasma, can
manipulate host reproduction and sex determination. Four major reproductive
manipulation types are distinguished: cytoplasmic incompatibility, thelytokous
parthenogenesis, male killing, and feminization. In this review, the effects of
these manipulation types and how they interfere with arthropod sex determination
in terms of host developmental timing, alteration of sex determination, and
modification of sexual differentiation pathways are summarized. Transitions
between different manipulation types occur frequently which suggests that they
are based on similar molecular processes. It is also discussed how mechanisms of
reproductive manipulation and host sex determination can be informative on each
other, with a special focus on haplodiploidy. Future directions on how the study
of endosymbiotic manipulation of host reproduction can be key to further studies
of arthropod sex determination are shown.
PMID- 24355930
TI - Variations in the management of asymptomatic adolescent grade 2 or 3 left
varicoceles: a survey of practitioners.
AB - OBJECTIVE: Our study aims to evaluate variations in management of asymptomatic
adolescent grade 2 and 3 varicoceles by pediatric urologists. SUBJECTS AND
METHODS: Electronic survey of all 267 current members of AAP Urology with 74
(28%) responding. RESULTS: When managing patients with positive examination
findings, 49% of surveyed practitioners use scrotal sonography as initial
screening, while 38% use only manual orchidometry and 11% observation with serial
examinations. If significant testicular size discrepancy is identified, 32%
immediately intervene surgically, while 59% repeat measurements in 6-12 months.
When no discrepancy is identified, 36.6% of practitioners discharge their
patients with no follow-up, 22.5% refer to an infertility specialist, and 31%
evaluate with semen analysis. Fifty-seven percent of practitioners have never
sent patients for semen analysis; only 4% send >50% of patients. Of these, 52%
and 27% analyzed semen at 17-18 years and 19-20 years, respectively, and 10% send
for semen analysis at <17 years. CONCLUSIONS: Our survey demonstrates that there
does not appear to be a consensus among pediatric urologists managing
asymptomatic grade 2 and 3 varicoceles. Better understanding of which adolescent
patients with varicoceles will go on to develop male infertility is necessary to
identify pediatric patients who could benefit from early intervention.
PMID- 24355932
TI - OPN gene polymorphism and the serum OPN levels confer the susceptibility and
prognosis of ischemic stroke in Chinese patients.
AB - AIM: To investigate the association of Osteopontin (OPN) gene polymorphism and
serum thrombin-cleaved OPN level with the susceptibility to ischemic stroke (IS)
and its prognosis. METHODS: A total of 377 patients with IS and 551 healthy
individuals were recruited. The OPN gene polymorphisms at -156 G>GG, -443 C>T and
-66 T>G were genotyped. Serum full-length and the thrombin-cleaved OPN were
determined. RESULTS: We found that only the -443 C>T polymorphism was
significantly associated with the susceptibility to IS. The -443 CC represented a
near 2 time higher risk for IS incidence than TT carriers. Also, the -443 CC
genotype had significantly poorer outcome and they significantly had higher
occurrence for bad recovery as determined by modified Rankin Scale (mRS)
(OR=2.18, p=0.043) and Barthel Index (BI) (OR=2.12, p=0.05). The mean serum
thrombin-cleaved OPN level in IS group were significantly higher than that in
control group. ROC analysis showed that the thrombin-cleaved OPN level (cut-off
value, 166.8 ng/ml) can discriminate IS patients from controls with a specificity
of 86.3% and a sensitivity of 57.7%. The serum thrombin-cleaved OPN was
significantly associated with the clinical outcome at 12 months after discharge
from hospital. CONCLUSION: These results suggest that the -443 C>T polymorphism
of OPN gene and serum thrombin-cleaved OPN can be used as a biomarker for the
susceptibility and prognosis of IS patients.
PMID- 24355931
TI - Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV
spike protein with deglycosylated forms as a SARS vaccine candidate.
AB - Development of vaccines for preventing a future pandemic of severe acute
respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV) and for
biodefense preparedness is urgently needed. Our previous studies have shown that
a candidate SARS vaccine antigen consisting of the receptor-binding domain (RBD)
of SARS-CoV spike protein can induce potent neutralizing antibody responses and
protection against SARS-CoV challenge in vaccinated animals. To optimize
expression conditions for scale-up production of the RBD vaccine candidate, we
hypothesized that this could be potentially achieved by removing glycosylation
sites in the RBD protein. In this study, we constructed two RBD protein variants:
1) RBD193-WT (193-aa, residues 318-510) and its deglycosylated forms (RBD193-N1,
RBD193-N2, RBD193-N3); 2) RBD219-WT (219-aa, residues 318-536) and its
deglycosylated forms (RBD219-N1, RBD219-N2, and RBD219-N3). All constructs were
expressed as recombinant proteins in yeast. The purified recombinant proteins of
these constructs were compared for their antigenicity, functionality and
immunogenicity in mice using alum as the adjuvant. We found that RBD219-N1
exhibited high expression yield, and maintained its antigenicity and
functionality. More importantly, RBD219-N1 induced significantly stronger RBD
specific antibody responses and a higher level of neutralizing antibodies in
immunized mice than RBD193-WT, RBD193-N1, RBD193-N3, or RBD219-WT. These results
suggest that RBD219-N1 could be selected as an optimal SARS vaccine candidate for
further development.
PMID- 24355934
TI - Arterial spin labeling perfusion MRI in children and young adults with previous
ischemic stroke and unilateral intracranial arteriopathy.
AB - BACKGROUND: Little is known about cerebral blood flow (CBF) in young patients
with ischemic stroke caused by an intracranial arteriopathy. Arterial spin
labeling (ASL) perfusion is a noninvasive technique for measuring CBF. We aimed
to investigate whether, in young patients with unilateral intracranial
arteriopathy and previous ischemic stroke, CBF is compromised in noninfarcted
brain areas of the symptomatic hemisphere and whether this is related to the
severity of the arteriopathy. METHODS: Patients aged 5-50 years, with previous
middle cerebral artery (MCA) territory infarction and a unilateral intracranial
arteriopathy, underwent magnetic resonance imaging (MRI), MR angiography and
pseudocontinuous ASL perfusion MRI. We assessed the severity of stenosis of
arteries that fed the symptomatic MCA territory, quantified CBF in the
noninfarcted cortex of both MCA territories and generated CBF maps for visual CBF
interpretation. RESULTS: A total of 17 patients were included (median age 29
years, range 5-49, 29% male). We found a similar median quantified CBF in the
symptomatic and asymptomatic MCA territories (86 ml.100 g(-1).min(-1)). CBF maps
showed hypoperfusion in the symptomatic MCA territory in 59% of patients compared
to 18% based on quantified CBF. Patients with a severe arteriopathy more often
showed hypoperfusion on CBF maps than patients with a mild arteriopathy. In 53%
of patients, small foci of increased signal intensity were visible on CBF maps
around an area of hypoperfusion, indicating vascular artifacts. In these
patients, we found large intraindividual variation in the quantified CBF in the
symptomatic hemisphere. In 47% of patients, the visual interpretation of
perfusion did not correspond with the quantified CBF. CONCLUSIONS: This study
shows that more than half of young patients with previous ischemic stroke in the
MCA territory and a unilateral intracranial arteriopathy have hypoperfusion in
the noninfarcted cortex of the symptomatic hemisphere when CBF is visually
assessed using a CBF map, in particular in patients with a severe arteriopathy.
In the same patients, quantification of CBF shows hypoperfusion in the
symptomatic hemisphere in only 18%. This discrepancy is caused by labeled blood
within the arteries that has not yet reached the tissue at the time of imaging.
Visual assessment can show hypoperfusion, while the quantified CBF in a similar
region appears higher when the intravascular labeled blood is included in the
region of interest. Further research should focus on elucidating whether cerebral
perfusion deficits in young stroke patients with intracranial arteriopathy might
help to identify patients who are at risk of poor outcome or stroke recurrence.
PMID- 24355935
TI - The management of thyroid nodules: a retrospective analysis of health insurance
data.
AB - BACKGROUND: In Germany, about 59 000 thyroid operations are performed each year
for uni- or multinodular goiter, most of them for diagnostic purposes. The rate
of detection of thyroid cancer in such operations is relatively low, at 1:15.
Evidence suggests that the preoperative tests recommended in guidelines for
estimating the risk of cancer are not being performed as often as they should. In
the present study, we determined the measures that were actually taken to
diagnose and treat thyroid nodules and compared the findings with the guideline
recommendations. METHOD: We retrospectively analyzed data from a single, large
statutory healthinsurance carrier in Germany (AOK), determining the diagnostic
and therapeutic measures that were reimbursed for 25 600 patients in whom a uni-
or multinodular goiter was newly diagnosed in the second quarter of 2006 (none of
these patients had carried such a diagnosis 1 year previously). We recorded the
diagnostic measures performed in the preceding 9 months and all other tests and
treatments, including surgery and radioactive iodine treatment, in the 2 years
thereafter. RESULTS: Among patients who underwent surgery for uninodular goiter,
the preoperative diagnostic studies included ultrasonography (in 100% of
patients), scintigraphy (94%), measurement of thyroid-stimulating hormone (95%),
measurement of calcitonin (9%), and fine-needle aspiration cytology (FNAC)(21%).
An ultrasonographic examination was billed for only 28% of patients with
uninodular goiter in the two years after the diagnosis was made. 13% of patients
with uninodular goiter who were not operated on were given L-thyroxine, even
though this is against guideline recommendations. CONCLUSION: Inadequate
preoperative risk stratification of thyroid nodules may explain the large number
of thyroid operations that are performed for diagnostic purposes, resulting in a
low percentage of malignancies detected. Preoperative FNAC and calcitonin
measurement should be used in the diagnostic evaluation of thyroid nodules far
more often than this is now done. As a rule, follow-up ultrasonography should be
performed for all thyroid nodules that are not operated on. Patients with non
operated thyroid nodules should not be given thyroxine. A limitation of this
study is that diagnostic measures were only recorded if they were performed in
the 9 months before surgery, with earlier diagnostic measures (if any) being
missed.
PMID- 24355936
TI - The diagnosis and treatment of celiac disease.
AB - BACKGROUND: Celiac disease is an inflammatory disease of, the small intestine
with a prevalence of roughly 0.5%-1%. Its symptoms arise in response to gluten
consumption by genetically predisposed persons (HLA-DQ2/8). The autoantigen
tissue transglutaminase (TG2) plays an important role in the pathogenesis of
celiac disease. METHOD: Selective review of pertinent literature, including
guidelines from Germany and abroad. RESULTS: Celiac disease can present at any
age with gastrointestinal or extraintestinal manifestations (e.g., malabsorption
or Duhring's dermatitis herpetiformis); it can also be found in association with
other (auto-)immune diseases, such as type 1 diabetes. Most cases are
oligosymptomatic. The wide differential diagnosis includes food intolerances,
intestinal infections, and irritable bowel syndrome, among other conditions. The
definitive diagnosis requires the demonstration of celiac disease-specific
autoantibody to TG2 (endomysium), which is over 90% sensitive and far over 90%
specific, and the characteristic histologic lesions of the small-bowel mucosa and
remission on a gluten-free diet. CONCLUSION: An understanding of celiac disease
ought to inform everyday clinical practice in all medical disciplines, because
this is a common condition with diverse manifestations that can be effectively
diagnosed and easily treated for the prevention of both acute and long-term
complications. Patients should follow a strictly gluten-free diet for life.
PMID- 24355938
TI - The role of equilibrium volume and magnetism on the stability of iron phases at
high pressures.
AB - The present study provides new insights into the pressure dependence of magnetism
by tracking the hybridization between crystal orbitals for pressures up to 600
GPa in the known hcp, bcc and fcc iron. The Birch-Murnaghan equation of state
parameters are; bcc: V0 = 11.759 A(3)/atom, K0 = 177.72 GPa; hcp: V0 = 10.525
A(3)/atom, K0 = 295.16 GPa; and fcc: V0 = 10.682 A(3)/atom, K0 = 274.57 GPa.
These parameters compare favorably with previous studies. Consistent with
previous studies we find that the close-packed hcp and fcc phases are non
magnetic at pressures above 50 GPa and 60 GPa, respectively. The principal
features of magnetism in iron are predicted to be invariant, at least up to ~6%
overextension of the equilibrium volume. Our results predict that magnetism for
overextended fcc iron disappears via an intermediate spin state. This feature
suggests that overextended lattices can be used to stabilize particular magnetic
states. The analysis of the orbital hybridization shows that the magnetic bcc
structure at high pressures is stabilized by splitting the majority and minority
spin bands. The bcc phase is found to be magnetic at least up to 600 GPa;
however, magnetism is insufficient to stabilize the bcc phase itself, at least at
low temperatures. Finally, the analysis of the orbital contributions to the total
energy provides evidence that non-magnetic hcp and fcc phases are likely more
stable than bcc at core earth pressures.
PMID- 24355937
TI - IQGAP1 is a key node within the small GTPase network.
AB - Coordination of the activity of multiple small GTPases is required for the
regulation of many physiological processes, including cell migration. There are
now several examples of functional interplay between small GTPase pairs, but the
mechanisms that control GTPase activity in time and space are only partially
understood. Here, we build on the hypothesis that small GTPases are part of a
large, integrated network and propose that key proteins within this network
integrate multiple signaling events and coordinate multiple small GTPase
activities. Specifically, we identify the scaffolding protein IQGAP1 as a master
regulator of multiple small GTPases, including Cdc42, Rac1, Rap1, and RhoA. In
addition, we demonstrate that IQGAP1 promotes Arf6 activation downstream of beta1
integrin engagement. Furthermore, following literature-curated searches and
recent mass spectrometric analysis of IQGAP1-binding partners, we report that
IQGAP1 recruits other small GTPases, including RhoC, Rac2, M-Ras, RhoQ, Rab10,
and Rab5, small GTPase regulators, including Tiam1, RacGAP1, srGAP2 and HERC1,
and small GTPase effectors, including PAK6, N-WASP, several sub-units of the
Arp2/3 complex and the formin mDia1. Therefore, we propose that IQGAP1 acts as a
small GTPase scaffolding platform within the small GTPase network, and recruits
and/or regulates small GTPases, small GTPase regulators and effectors to
orchestrate cell behavior. Finally, to identify other putative key regulators of
small GTPase crosstalk, we have assembled a small GTPase network using protein
protein interaction databases.
PMID- 24355939
TI - Transcribed oxygen saturation vs oximeter recordings in very low birth weight
infants.
AB - OBJECTIVE: The objective of this study was to compare hand-transcribed oxygen
saturation (SpO2) with electronic oximeter data in very low birth weight infants
(VLBWI, <1500 g). STUDY DESIGN: Oximeter data were downloaded from birth through
36 weeks postmenstrual age (PMA) for VLBWI before and after interventions to
improve neonatal intensive care unit oxygen management. Transcribed SpO2 values
were obtained by chart review. Proportions of transcribed and oximetry data in
target (85 to 93%), hypoxemic (80 to 84%), and hyperoxemic (>=98%) ranges before
and after intervention were compared. RESULT: There were 30,441 oximetry hours
before intervention and 54,538 oximetry hours after intervention. Transcribed
SpO2 values correlated strongly with oximeter overall. However, during hours on
supplemental oxygen, transcribed values significantly overdocumented target range
and underdocumented values 80 to 84 and >=98%. This finding varied by respiratory
support and PMA, and increased after intervention. CONCLUSION: Transcribed SpO2
values overdocumented target range and underdocumented hyperoxemic and hypoxemic
ranges compared with electronic oximeter data. These results support
incorporating electronic oximeter data into medical records.
PMID- 24355940
TI - Obesity during pregnancy alters maternal oxidant balance and micronutrient
status.
AB - OBJECTIVE: Little is known about the effect of obesity on inflammatory status in
pregnant women. The objective of this study was to determine the effect of
obesity on markers of inflammation, oxidative stress and micronutrient status in
obese pregnant women and their infants compared with lean controls (Lc). STUDY
DESIGN: This was a prospective case-control study. A total of 15 obese (Ob; body
mass index (BMI) >30 kg m(-2)) and 15 lean (BMI 18-25 kg m(-2)) women were
recruited based on prepregnancy BMI. Vitamins A, B6, C, E and 25-hydroxyvitamin D
(25(OH)D), zinc, red blood cell (RBC) folate, C-reactive protein (CRP),
interleukin-6 (IL-6), tumor necrosis factor-alpha and oxidized and reduced
glutathione were measured from maternal blood between 24 and 28 weeks of
gestation. Vitamins A, B6, C and E, 25(OH)D, zinc, red blood cell folate, CRP and
IL-6 were measured from cord blood at delivery. RESULT: Ob pregnant women have
statistically significantly lower levels of vitamin B6, vitamin C, vitamin E, RBC
folate, higher CRP and IL-6 levels and higher ratio of oxidized to reduced
glutathione compared with Lc pregnant women. Infants born to Ob mothers did not
have statistically significantly higher measures of inflammation or oxidative
stress. There were no differences in micronutrient concentrations between Lc and
Ob infants, but folate, vitamin B6 and zinc levels correlated strongly between
mother and infant. There was no statistically significant difference in any
parameter between Ob and Lc cord blood. CONCLUSION: Ob pregnant women have
increased inflammation and oxidative stress, and lower levels of nutritional
antioxidant defenses compared with Lc pregnant women. We speculate that lower
antioxidant defenses combined with increased oxidative stress and inflammation
may contribute to the adverse outcomes associated with pregnancy in Ob women.
PMID- 24355942
TI - Coagulase-negative staphylococcus sepsis in preterm infants and long-term
neurodevelopmental outcome.
AB - OBJECTIVE: The objective of this study was to examine the impact of Coagulase
negative staphylococcus (CoNS) sepsis in preterm infants on the
neurodevelopmental outcomes at 30 to 42 months corrected age (CA). STUDY DESIGN:
This is a retrospective cohort study. All preterm infants born at <29 weeks
gestational age between 1995 and 2008 and had a neurodevelopmetnal assessment at
30 to 42 months CA were eligible. The neurodevelopmetnal outcomes of infants
exposed to CoNS sepsis were compared with infants unexposed to any type of
neonatal sepsis. RESULT: A total of 105 eligible infants who were exposed to CoNS
sepsis were compared with 227 infants with no neonatal sepsis. In univariate
analysis, infants with CoNS sepsis were more likely to have total major
disability (odds ratio (OR)=1.9; 95% CI: 1.07 to 3.38) and cognitive delay
(OR=2.53; 1.26 to 5.14).There was no significant difference in the incidence of
cerebral palsy, blindness and deafness between the two groups. After correcting
for potential confounders, CoNS sepsis was associated with increased risk of
cognitive delay (adjusted odds ratio (aOR)= 2.23; 95% CI 1.01 to 4.9), but not
with the total major disability (aOR=1.14; 95% CI: 0.55 to 2.34). CONCLUSION: Our
study suggests that CoNS sepsis in preterm infants might be associated with
increased risk for cognitive delay at 36 months CA.
PMID- 24355941
TI - Acute pancreatitis during pregnancy: a review.
AB - This article aims to draw together recent thinking on pregnancy and acute
pancreatitis (AP), with a particular emphasis on pregnancy complications, birth
outcomes and management of AP during pregnancy contingent on the etiology. AP
during pregnancy is a rare but severe disease with a high maternal-fetal
mortality, which has recently decreased thanks to earlier diagnosis and some
maternal and neonatal intensive care improvement. AP usually occurs during the
third trimester or the early postpartum period. The most common causes of AP are
gallstones (65 to 100%), alcohol abuse and hypertriglyceridemia. Although the
diagnostic criteria for AP are not specific for pregnant patients, Ranson and
Balthazar criteria are used to evaluate the severity and treat AP during
pregnancy. The fetal risks from AP during pregnancy are threatened preterm labor,
prematurity and in utero fetal death. In cases of acute biliary pancreatitis
during pregnancy, a consensual strategy could be adopted according to the
gestational age, and taking in consideration the high risk of recurrence of AP
(70%) with conservative treatment and the specific risks of each treatment. This
could include: conservative treatment in first trimester and laparoscopic
cholecystectomy in second trimester. During the third trimester, conservative
treatment or endoscopic retrograde cholangiopancreatography with biliary
endoscopic sphincterotomy, and laparoscopic cholecystectomy in early postpartum
period are recommended. A multidisciplinary approach, including
gastroenterologists and obstetricians, seems to be the key in making the best
choice for the management of AP during pregnancy.
PMID- 24355944
TI - Superior vena cava isolation by right pulmonary vein ablation.
PMID- 24355945
TI - Instrumental exams performance can be a contributing factor to the delay in
diagnosis of migraine.
AB - BACKGROUND: Diagnostic delay is a recognized drawback for a correct management of
migraine patients. The aim of this study was to investigate the possible
relationship among number and type of examinations performed and diagnostic delay
in migraine diagnosis. METHODS: We enrolled 500 subjects referred to our Headache
Center for a migraine without aura. We analyzed the relationship among diagnostic
delay, number of examinations performed and performance of each single test by a
Cox regression model and an ordinal logistic regression model. RESULTS: Each
individual exam increased a diagnostic delay of at least 12 months (p < 0.05, Cox
regression model). Brain CT as the first diagnostic approach had a reduced risk
of delay of more than 5 years (OR 0.632, 95% CI 0.71-0.56, p < 0.05, ordinal
regression model). CONCLUSIONS: The number of instrumental examinations seems to
significantly influence the diagnostic delay. This aspect contributes to increase
health care costs, the risk of pain chronicization and pharmacological treatment
misuse.
PMID- 24355943
TI - Angiogenic cytokines profile in smoldering multiple myeloma: no difference
compared to MGUS but altered compared to symptomatic myeloma.
AB - BACKGROUND: Symptomatic multiple myeloma (MM) evolves from an asymptomatic
precursor state termed monoclonal gammopathy of undetermined significance (MGUS)
and smoldering myeloma (SMM). Angiogenesis plays a key role in the pathogenesis
of MM but there are very limited data for angiogenesis in SMM. MATERIAL AND
METHODS: We measured the circulating levels of angiopoietin-1 (Ang-1),
angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and angiogenin
in 54 patients with SMM. The results were compared with those of 27 MGUS
patients, 55 MM patients, and 22 healthy controls. The expression of VEGF-A gene
was also evaluated in 10 patients with SMM, 10 with symptomatic MM, and 10 with
MGUS. RESULTS: The ratio of circulating Ang-1/Ang-2 was reduced in MM patients
with symptomatic disease due to a dramatic increase of Ang-2 (p<0.001), but not
in patients with SMM or MGUS, in whom it did not differ compared to controls.
VEGF and angiogenin were increased in all patients compared to controls. However,
circulating VEGF was higher in symptomatic MM compared to SMM and MGUS, while
angiogenin was reduced. There were no differences in the expression of VEGF-A
among the 3 patients categories. CONCLUSIONS: SMM has a circulating angiogenic
cytokine profile similar to that of MGUS, but has altered profile compared to
symptomatic MM. Thus, in the progression of MGUS to SMM, circulating angiogenic
cytokines seem to be the same. On the contrary, in symptomatic myeloma, the
alterations of angiopoietins along with VEGF contribute to myeloma cell growth,
supporting the target of these molecules for the development of novel anti
myeloma agents.
PMID- 24355946
TI - FDI: From research representation to action.
PMID- 24355947
TI - From the Editor's desk--STAR program.
PMID- 24355948
TI - Filling lateral canals: influence of calcium hydroxide paste as a root canal
dressing.
AB - CONTEXT: The use of intracanal medication aims to provide antimicrobial activity
in the root canal system, leading to a more satisfactory condition for root canal
obturation. However, it is important to evaluate whether such medication would
affect the sealing-off from the main root canal of ramifications such as lateral
canals. AIM: Evaluate the influence of calcium hydroxide [Ca(OH)2] paste on the
filling of lateral canals. SETTINGS AND DESIGN: Ex vivo quantitative laboratory
study. MATERIALS AND METHODS: Sixty single-rooted teeth with lateral canals
created were used, 10 teeth per group. Group A was described respectively as
lateral condensation technique (subgroup 1), thermomechanical compaction
(subgroup 2), and continuous wave of condensation (subgroup 3). In Group B,
subgroups 4, 5, and 6 were filled with Ca(OH)2 for 7 days before filling using
the techniques applied in subgroups 1, 2, and 3. Radiographic evaluation was
performed to count the number of filled lateral canals in each group. The teeth
were cross-sectioned over the lateral canals; thus, 180 specimens were obtained.
Each specimen was immersed in a polyester resin. Digital images were obtained and
specific software (Image Tool; ) was used to evaluate the number of obturated
lateral canals and the filling length in each lateral canal of groups.
STATISTICAL ANALYSIS USED: Data were statistically analyzed using SPSS 12.0 for
Windows (Descriptive statistical analysis and Newman-Keuls test). RESULTS: A
greater number of simulated lateral canals were filled in Group A (91.1%). Group
B had less filled lateral canals (33.3%). The sealing of lateral canals was
statistically different between Group B (26.15%) and Group A (74.43%).
CONCLUSIONS: According to the radiographic analysis and the linear filling
measurement, the use of Ca(OH)2 decreased the number and the length of sealed
lateral canals.
PMID- 24355950
TI - Antibacterial efficacy of sodium hypochlorite with a novel sonic agitation
device.
AB - OBJECTIVE: The aim of this study is to evaluate the antibacterial efficacy of 3%
sodium hypochlorite (NaOCl) with sonic agitation devices. MATERIALS AND METHODS:
Fifty extracted human single-rooted teeth were collected. Canals were prepared up
to Profile #35/0.06. Forty teeth were inoculated with Enterococcus faecalis and
incubated for 24 hours. The teeth were then divided into five groups based on the
agitation device used. Group 1- was agitated with EndoActivator. Group 2 was
agitated with Waterpik Power Flosser. In Group 3, Waterpik flosser was used with
a nickel-titanium file. Group 4 (positive control) was not subjected to any
agitation, and Group 5 -was the negative control. Superficial and deep dentinal
shavings were collected from coronal and apical halves and sowed in brain heart
infusion (BHI) agar to evaluate colony-forming units (CFU/mL). RESULTS: Krusal
Wallis, analysis of variance (ANOVA) and Mann-Whitney U test showed that Group 3
showed a smaller number of CFUs/mL Group 2 showed a relatively greater number of
CFU/mL. The deep apical dentin areas showed more number of CFUs relative to other
sites. CONCLUSION: The nickel-titanium file attached to the Waterpik Power
Flosser system was found to be as effective as the EndoActivator in antibacterial
efficacy against E.faecalis.
PMID- 24355949
TI - Effect of Lippia sidoides in mouthrinses on de novo plaque formation: a double
blind clinical study in humans.
AB - AIM: The aim of this study was to evaluate the antiplaque effect of Lippia
sidoides (LS) by in vivo investigation. MATERIALS AND METHODS: Ten healthy
volunteers participated in a cross-over, double-blind clinical study, using a 3
day partial-mouth plaque accumulation model. The participants abolished any
method of mechanical oral hygiene and they were randomly assigned initially to
use just the following mouth rinses: Distilled water (negative control group),
0.12% chlorhexidine digluconate (positive control group) or 10% LS (test group).
The plaque index was recorded in the six anterior upper teeth at the end of the
trial and the one-way ANOVA and Bonferroni tests were used to estimate the
difference among groups. RESULTS: The clinical results did show statistically
significant difference among three groups (P < 0.05), favoring the positive
control group and test group, however, no difference in efficacy was found
between them (P > 0.05). CONCLUSIONS: The mouth rinses containing 0.12%
chlorhexidine digluconate and 10% LS were equally able to inhibit plaque re
growth.
PMID- 24355951
TI - Evaluation of accuracy of portable fingertip pulse oximeter, as compared to that
of a hospital oximeter with digital sensor.
AB - CONTEXT: The pulse oximeter is a device that noninvasively provides continuous
information about the peripheral oxygen saturation (SpO2) rate. This device is
utilized in the detection of hypoxemia, due to its able to sense changes in
hemoglobin oxygen saturation. AIMS: The objective of this study was to verify the
accuracy of the Choice(r) Medical MD300C3 Fingertip Pulse Oximeter, as compared
to that of a hospital oximeter coupled with a Drager(r) Infinity Delta monitor,
with the purpose of using this first methodology in dental procedures to monitor
the peripheral oxygen saturation (SpO2) of patients submitted to dental
treatments. MATERIALS AND METHODS: Fifty-five adult patients, both genders, were
selected in the Santa Casa Hospital of Maringa, Brazil. The volunteers did not
present cardiac problems, prosthetic cardiac valves, pacemakers, or pulmonary
diseases, and were not pregnant or children. Each patient received a portable
fingertip pulse oximeter (PPO) on the middle finger of the left hand and the
hospital oximeter (control device) on the forefinger of the same hand. A total of
six measurements were developed. The Pearson correlation coefficient and the
Bland and Altman method was used to calculate the statistical analysis. RESULTS:
No statistically significant difference was found between the measurements taken
by the utilized devices. The average of comparative analysis presented by the
devices was 0.2337 +/- 0.4355 (mean +/- SD), suggesting a strong correlation
between the obtained results. CONCLUSION: According to the methodology of the
research, the PPO has similar accuracy to the conventional hospital oximeter with
digital sensor. The PPO can be used in dental treatments.
PMID- 24355952
TI - Probiotics for future caries control: a short-term clinical study.
AB - OBJECTIVES: To compare mutans streptococci levels in saliva, before and after
consumption of probiotic ice-cream and curds. MATERIALS AND METHODS: Forty caries
free children in the age group of 12-14 years were selected and equally divided
into four groups I, II, III, IV. Children in group I and II were given 100 ml
probiotic ice-cream and plain ice cream respectively and group III and IV were
given 100 ml probiotic curd and plain curd respectively for a period of 7 days.
Saliva samples were assessed at baseline, 1 hour after consumption and after 7
days intervention period using Mitis salivarius Bacitracin agar. The number of
colonies was counted and subjected to statistical analysis. RESULTS: The study
revealed a reduction in salivary mutans streptococci (MS) counts after 1 hour in
all the groups. However after 7 days, probiotic ice-cream and curd showed a
statistically significant (P < 0.001) reduction in MS counts as compared to the
control ice cream and curd. The difference in the reduction of MS counts with
probiotic ice-cream and probiotic curd at 1 hour and 7 days was not statistically
significant. CONCLUSION: The use of probiotic products could be an alternative
strategy of displacing pathogenic microorganisms by probiotic bacteria and can
thus be exploited for the prevention of enamel demineralization.
PMID- 24355953
TI - A study to correlate the incidence of cross arch balance and working side
occlusal wear facets among different age groups: an in vivo study.
AB - INTRODUCTION: The prevalence of group function and canine guided occlusion is
common in natural dentition, but cross arch balance is not often seen. Hence, a
study was carried out with following objectives: Analysis of incidence of cross
arch balance in different age groups and working side occlusal wear facets in
following subjects. MATERIALS AND METHODS: A total of 200 patients with natural
dentition were included in the study. Subjects with cross arch balance were
analyzed for working side occlusal wear facets. Data were analyzed statistically
by Chi-square test. RESULTS: The incidence of cross arch balance in the study
group was 0.7%. On examination, subjects with group function on the working side
and cross arch balance on the non-working side had more occlusal wear facets.
CONCLUSION: From the study, it was observed that there was no significant
variation in the number and extent of wear facets between the cross arch and
without cross arch subjects due the smaller sample size hence it was difficult to
conclude the relationship non-working side contact as interference and its
influence in wearing of dentition in this study.
PMID- 24355954
TI - Radiological analysis of the relationship between occlusal tooth wear and
mandibular alveolar bone density and height.
AB - AIM: The aim of this study was to examine the relationship between occlusal tooth
wear and mandibular alveolar bone density (ABD) and alveolar bone height (ABH)
using computer-assisted densitometric image analysis (CADIA) program. MATERIALS
AND METHODS: The study was comprised of 134 mandibular first molar teeth in 90
patients with various degrees of occlusal tooth wear. The degree of tooth wear
was classified according to the tooth wear index (TWI). Periodontal examinations
were performed on all patients and included plaque index, gingival index, probing
depth, and clinical attachment loss measurements. ABD and ABH were measured from
intraoral digital periapical radiographs and analyzed using CADIA. RESULTS: No
increases in ABD were observed between TWI 0 and TWI 1 or between TWI 0 and TWI 2
(P > 0.05). However, increases in ABD were observed between TWI 0 and TWI 3 (P <
0.01), TWI 1 and TWI 3 (P < 0.01), TWI 1 and TWI 2 (P < 0.05) and TWI 2 and TWI 3
(P < 0.05). In addition, ABH was found to increase with increase in wear, with
the exception of the interval between TWI 0 and TWI 1. CONCLUSIONS: Occlusal
tooth wear does not result in any radiologically identifiable changes in the
alveolar bone during the initial stages of wear; however, significant increases
in both ABD and ABH may be observed as tooth wear progresses.
PMID- 24355955
TI - Risk of musculoskeletal disorders in upper limbs in dental students: concordance
of different methods for estimation of body angle.
AB - AIMS: The purpose of this paper was to evaluate the agreement among different
methods used to estimate angular deviation of the body to determine the risk for
development of upper limb musculoskeletal disorders in dentistry undergraduates.
MATERIALS AND METHODS: Students (n = 79) enrolled in the final year undergraduate
course of the Araraquara School of Dentistry-Syo Paulo State University-UNESP
were evaluated. Photographs were taken of students performing clinical
procedures. The work postures adopted by each student were evaluated by means of
rapid upper limb assessment (RULA). The basis used to obtain the individual's
final risk score is the measurement of the angular deviations in the neutral
positions of the regions evaluated. Two methods were used to estimate the angular
deviation of the body: Visual exam and Image Tool software. A RULA final risk
score was attributed to each procedure the student performed (n = 333). Study of
the agreement between the methods about risk of musculoskeletal disorders was
conducted by means of Kappa (kappa) statistics. The level of significance adopted
was 5%. RESULTS: Fair agreement (kappa = 0.32) between the evaluated methods was
verified. CONCLUSION: The risk for development of upper limb musculoskeletal
disorders by dentistry undergraduates evaluated by using RULA was not in
agreement with the results obtained by use of visual exam and Image Tool.
PMID- 24355956
TI - Effect of sialagogue on bleeding on probing in Sjogren's syndrome.
AB - BACKGROUND: Bleeding on probing (BOP) is a frequent observation in patients with
Sjogren's syndrome and a sialagogue is routinely prescribed for these patients.
OBJECTIVE: The objective of this study was to evaluate the effect of sialagogue
(muscarinic cholinergic agonists) on BOP in patients with Sjogren's syndrome.
MATERIALS AND METHODS: This observational study included 57 subjects. Study
population was divided into two groups: Subjects on sialagogue (n = 32) and
subjects not on sialagogue due to their side-effects (non-sialagogue, n = 25).
The number of sites with BOP was recorded on all teeth. RESULTS: The subjects on
sialagogue had a significantly lower mean (standard error) number of sites with
BOP 22.97 (2.65) as compared with the non-sialagogue group 46.59 (6.20), P <
0.001. After adjusting for the use of remineralizing rinse the subjects on
sialagogue had a significantly lower number of sites with BOP (P < 0.001).
CONCLUSION: In this observational study treatment with sialagogue may prevent BOP
in patients with Sjogren's syndrome.
PMID- 24355957
TI - An insight into dentin desensitizing agents--in vivo study.
AB - AIMS: It is widely accepted that dentin hypersensitivity is an uncomfortable
condition, which affects the function and quality of life. This study determines
the difference in efficacy of four desensitizing agents. SUBJECTS AND METHODS: An
in vivo study was conducted to compare four dentin desensitizing agents on 40
patients. Age, sex, and place of the patient were recorded. Hydroxyapatite
containing agent, potassium nitrate containing, sodium fluoride containing, and
natural resin containing agents were used for the study. The baseline measurement
for pain perceived due to hypersensitivity was recorded by visual analog scale
(VAS). Then after application of the respective desensitizing agent, the last
score was taken after 7 days. STATISTICAL ANALYSIS USED: The agents were compared
in terms of mean differences in their VAS scale readings. Kruskall-Wallis test
and Mann-Whitney tests were used to compare the efficacies of the four agents.
RESULTS: The four desensitizing agents which contain different active agents were
effective in relieving dentin hypersensitivity. Not much significant difference
was found among the four. However, propolis (natural resin-containing agent)
showed better clinical response in patients among the four, followed by sodium
fluoride-containing agent. CONCLUSIONS: Propolis proves to be a good natural and
nontoxic option for treatment of dentin sensitivity.
PMID- 24355958
TI - Efficacy of silver diamine fluoride as an antibacterial as well as antiplaque
agent compared to fluoride varnish and acidulated phosphate fluoride gel: an in
vivo study.
AB - BACKGROUND: Silver diamine fluoride (SDF) is already proven as an antibacterial
agent in vitro. Present study was formulated to compare the efficacy of SDF as an
antibacterial as well as antiplaque agent in vivo with fluoride varnish and
acidulated phosphate fluoride (APF) gel. STUDY DESIGN: Total 123 children (male =
82, female = 41) were included in the study for a period of 18 months. Children
were divided into three different groups-Group 1: SDF; Group 2: fluoride varnish;
and Group 3: APF gel. All subjects were evaluated via plaque score at 6 th, 12
th, and 18 th months as well as Streptococcus mutans counts in saliva at 72 h, 6
th, 12 th, and 18 th months of follow-up. RESULTS: Significant reduction was
found in plaque score as well as S. mutans counts irrespective of group division.
On intergroup comparison, no statistically significant difference was found in
plaque score, but significant reduction in S. mutans counts was found in Group 1
as compared with Groups 2 and 3, while no significant difference was found
between Groups 2 and 3. CONCLUSION: In vivo application of SDF on enamel
significantly decreases S. mutans counts as compared to fluoride varnish and APF
gel.
PMID- 24355959
TI - Comparative analysis of gingival crevicular fluid neopterin levels in health and
periodontal disease: a biochemical study.
AB - BACKGROUND: Periodontitis involves intricate interactions of the biofilm with the
host immunoinflammatory response and subsequent alterations in bone and
connective tissue homeostasis. Neopterin is a marker, belonging to the class of
pteridines, which is associated with cell-mediated immunity. It is produced by
interferon-gamma stimulated macrophages. The levels of neopterin in body fluids
are elevated in infections, autoimmune diseases, malignancies and allograft
rejections. This investigation was designed to estimate the levels of neopterin
in gingival crevicular fluid (GCF) in health, chronic gingivitis and chronic
periodontitis. MATERIALS AND METHODS: Thirty subjects were divided into three
groups of ten subjects each as with healthy periodontium (Group 1), chronic
gingivitis (Group 2) and chronic periodontitis (Group 3). The GCF samples were
obtained from the subjects by placing color-coded calibrated, volumetric, micro
capillary pipettes extracrevicularly. The samples were placed in plastic vials
and stored at -70 degrees C until the time of neopterin estimation using enzyme
immunoassay. RESULTS: The mean neopterin level in Group 3 (126.28 +/- 37.70
nmol/L) is significantly higher than the mean neopterin level in Group 1 (48.66
+/- 18.82 nmol/L) and Group 2 (70.68 +/- 18.26 nmol/L) (P < 0.05). However, there
is no significant relationship between neopterin levels and various clinical
parameters in each study group (P > 0.05). CONCLUSIONS: The results of our study
indicate that the neopterin levels in GCF are positively associated with
periodontal disease, which may provide a useful tool in monitoring its
progression. Nevertheless, further longitudinal studies are required with larger
sample sizes in which neopterin levels are progressively estimated and compared
to baseline values.
PMID- 24355960
TI - Photography versus lateral cephalogram: role in facial diagnosis.
AB - CONTEXT: In a developing country like India, where expensive cephalometric
apparatus is unavailable everywhere, photography assumes importance for
diagnostic and treatment planning procedures as it is low cost and less technique
sensitive. AIMS AND OBJECTIVES: The aim of this study was to compare and
correlate craniofacial measurements from cephalometric radiographs with analogous
measurements from standardized facial photographs in the Gujarati population.
MATERIALS AND METHODS: The study was carried out using standardized cephalometric
radiographs and photographs of 60 Gujarati subjects (30 males, 30 females). Eight
facial landmarks were identified on both the photograph and cephalogram. Five
angular and three linear measurements were created from these landmarks and
planes. STATISTICAL ANALYSIS USED: The Pearson correlation coefficient was used
to estimate the correlations between the photographic and cephalometric
variables. The intraclass correlation coefficient (ICC) was estimated to measure
the reliability of the repeated tracings. RESULTS: On comparing the cephalometric
and photographic variables for the entire sample, positive and significant
correlations were found for all the variables studied (r > 0, P < 0.05). The ICCs
for all of the angular measurements were higher than those for linear
measurements. CONCLUSION: Photographs may be used reliably for epidemiological
purposes, screening, initial consultations and cases where irradiation is
contraindicated or needs to be avoided.
PMID- 24355961
TI - A clinical evaluation of 5% amlexanox oral paste in the treatment of minor
recurrent aphthous ulcers and comparison with the placebo paste: a randomized,
vehicle controlled, parallel, single center clinical trial.
AB - OBJECTIVES: The primary objective of the following study is to determine and
secondary objective is to compare the efficacy and safety of 5% amlexanox oral
paste in the treatment of recurrent minor aphthous ulcers and also to evaluate
the recurrence rate of aphthous ulcers over a period of 1 year. MATERIALS AND
METHODS: The present study was conducted on 100 patients diagnosed to have
recurrent minor aphthous ulcers of which, 50 patients were advised to apply 5%
amlexanox oral paste directly on the ulcer 4 times a day for 6 days and the other
50 patients were given placebo paste for the same duration. The baseline
parameters were recorded on the first visit which includes ulcer size, pain,
erythema and exudation. Efficacy and safety evaluations were made on the 4 th day
and 6 th day. In total 30 patients with increased frequency of ulcers were
advised to use 5% amlexanox paste for one whole year and the number of ulcers per
month was recorded to evaluate any decrease in the recurrence rate. RESULTS: Male
patients dominated the study with 73 males and 27 females. The mean age of the
total sample was 26.6 years. The amlexanox group showed marked reduction in ulcer
size (P < 0.001), significant reduction in the visual analog scale scores of pain
(P < 0.001), significant lower scores of erythema and exudation (P < 0.001) when
compared to the placebo group on the 6 th day of follow-up. The incidence of
recurrence of ulcers was significantly reduced up to the 6 th month, but
thereafter recurrence rate slowly increased. CONCLUSIONS: Almost 5% of Amlexanox
oral paste is clinically beneficial in reducing the pain, erythema, exudation and
size of the ulcer over a period of 6 days. There was no definite conclusion drawn
with respect to its effect on the recurrence rate of aphthous ulcers over a
period of 1 year.
PMID- 24355962
TI - Cervical lymph node metastasis in oral squamous cell carcinoma: a correlative
study between histopathological malignancy grading and lymph node metastasis.
AB - BACKGROUND: Histologic grading has been used as a prognostic factor and for
clinical behavior evaluation of oral squamous cell carcinoma for the past several
decades. At the same time, the prognostic value of different grading
classifications remains controversial. A major problem for most histopathological
grading systems is the intraobserver and interobserver disagreement. AIMS AND
OBJECTIVES: To validate the prognostic efficiency of the histologic assessment of
the primary tumor in predicting cervical metastasis, to identify those histologic
features in the tumor most closely associated with cervical metastasis and to
evaluate the reliability of the multifactorial grading (MFG) system by measuring
intraobserver and interobserver agreement using kappa statistic. MATERIALS AND
METHODS: A set of 60 cases were chosen at random out of the 292 squamous cell
carcinoma cases reported in our institution from 2007 to 2010. All cases were
graded according to: Modified Broders' descriptive system and Anneroth et al.,
MFG system. Two Pathologists independently graded the tumor forefront blinded to
the node metastasis. RESULTS: The MFG showed a significant relation between the
degree of histologic malignancy and presence of metastasis in the nodes. Among
the components of grading, a significant difference was observed in the nuclear
polymorphism and the pattern of invasion between the metastatic and non
metastatic patients. Intraobserver and interobserver agreement was acceptable and
satisfactory. CONCLUSIONS: Moderate to good agreement between observers greatly
increases the validity of the MFG system. The multifactorial malignancy grading
could serve as a predictor for metastasis in the cervical lymph nodes.
PMID- 24355963
TI - Color change of composite resins subjected to accelerated artificial aging.
AB - AIM: The aim of this study was to evaluate the influence of accelerated
artificial aging (AAA) on the color change of composite resins used in dentistry.
MATERIALS AND METHODS: Three composite resins were evaluated: Two microhybrids
and one hybrid of higher viscosity, with different amounts and sizes of filler
particles, shades C2 and B2. A total of 54 specimens were obtained (18 for each
composite resin), made of a Teflon matrix (15 mm in diameter and 2 mm in height).
The color measurements were obtained with a Spectrophotometer, (PCB 6807 BYK
Gardner) before and after AAA. Data were submitted to the Kolmogorov-Smirnov test
(alpha >0.05), ANOVA and Tukey test (alpha <0.05). After statistical analysis,
the color difference among composite resins with the same shades was analyzed.
RESULTS: All composite resins showed unacceptable color changes after AAA (DeltaE
> 3). Considering the variable ?E, it was observed that the color tone C2 was
already statistically different for the microhybrid composite resin prior to AAA
(P < 0.05) and in shade B2 for hybrid of higher viscosity and microhybrid with
barium glass fluoride aluminum and silica dioxide (P < 0.01). After this process,
a statistically significant difference was observed only for shade B2 between
microhybrid composite resins (P < 0.01) and for hybrid of higher viscosity and
microhybrid with barium glass fluoride aluminum and silica dioxide (P < 0.05).
Regarding the color difference within a same composite resin group, before aging
the composite resin hybrid of higher viscosity B2 showed the highest color
variation rate and microhybrid with zirconium/silica C2 showed the lowest.
CONCLUSIONS: All composite resins presented unacceptable color changes after 382
h of aging and different composite resins with same hue, presented different
colors before being subjected to the aging process (B2 and C2) and after (B2). It
was also observed color difference within a group of the same composite resin and
same hue.
PMID- 24355964
TI - Comparative evaluation of effect of laser on shear bond strength of ceramic
bonded with two base metal alloys: an in-vitro study.
AB - The most common clinical failure in metal ceramic restoration is at the ceramo
metal interface. For the clinical longevity, metal-ceramic prostheses must have
satisfactory bond strength between metal and ceramic. AIM AND OBJECTIVE: The aim
of this study is to evaluate the effect of Laser etching on shear bond strength
between base metal alloys and ceramic. MATERIALS AND METHODS: A total of 60
specimens were made (Base 5 mm diameter and 1 mm thickness, step with 4 mm
diameter and 4 mm in length). They were divided into three groups. Group A
control, Group B-sand blasting, and Group C-laser etching. The Surface
morphology, surface roughness, and wettability of the specimens were observed
under scanning electron microscope (SEM) Ceramic application was carried out
layer by layer for an optimal height of 4 mm. The shear bond strength test was
performed using a universal testing machine and the nature of the fracture was
examined under SEM. RESULTS: The mean shear bond strength values for laser etched
(Group C) Nickel-chromium (Ni-Cr) alloy bonded with ceramic was (49.12 +/- 7.12
MPa) and ceramic bonded with Cobalt-chromium (Co-Cr) was (50.04 +/- 4.27 MPa),
sand blasted (Group B) Ni-Cr alloy bonded with ceramic was (26.00 +/- 5.22 MPa),
and ceramic bonded with Co-Cr was 24.54 +/- 4.78 MPa. The SEM image after
debonding showed 10% of adhesive failure and 70% cohesive failure and 20% of both
adhesive and cohesive failure for Laser etching. However, there was no
significant difference in the values of shear bond strength between the two base
metal alloys in Group C. CONCLUSION: The s hear bond strength between ceramic
bonded with Ni-Cr alloys using the Laser etching as surface treatment was 49.12
+/- 7.12 MPa and for Co-Cr alloys 50.04 +/- 4.27 MPa. Laser surface treatment
produces an excellent surface roughness and achieved good shear bond strength
values and aid in achieving a better bond strength between metals and ceramic.
PMID- 24355965
TI - Effect of various commercially available mouthrinses on shear bond strength of
orthodontic metal brackets: an in vitro study.
AB - CONTEXT: Alcohol is known to degrade and dissolve the bisphenol A glycidyl
methacrylate present in the composite resin. The effect of alcohol containing
mouthrinses on the shear bond strength of orthodontic metal brackets bonded with
composite resin has not been verified until date and is the purpose of this
study. AIMS: The aims and objectives of the present study were to evaluate (1)
Whether there is a significant difference in the shear bond strength of metal
orthodontic brackets after the 1 year (12 h) and 2 years simulation (24 h) of
mouth rinsing with 4 different commercially available mouthrinses (2 alcoholic
and 2 alcohol-free mouthrinses) when compared to the control. (2) Whether alcohol
containing mouthrinses have more adverse effect on the shear bond strength when
compared with alcohol-free mouthrinses. (3) To assess the site of bond failure
using adhesive remnant index. SETTING AND DESIGN: Experimental - laboratory
based. MATERIALS AND METHODS: A total of 100 upper premolars extracted for
orthodontic purpose were collected immediately after extraction, cleared soft
tissue debris and blood and immediately stored in distilled water with 0.1%
thymol crystals added to inhibit bacterial growth. Two alcohol containing
mouthrinses and two alcohol-free mouthrinses were used and the bonded teeth were
placed in the mouthrinses for a stipulated period of time (1 year simulation and
2 years simulation) and shear bond strength were tested using Lloyd Universal
Testing Machine. STATISTICAL ANALYSIS USED: The data were analyzed using analysis
of variance and paired samples t-test. RESULTS: After the 1 year and 2 years
simulation time, samples stored in alcohol containing mouthrinses showed lower
bond strength (P < 0.05) when compared to samples stored in alcohol free
mouthrinses and distilled water (control). CONCLUSION: Alcohol containing
mouthrinses affect the shear bond strength of the metal orthodontic brackets
bonded with composite resin (Transbond XT in the present study), more when
compared with alcohol-free mouthrinses. It is, therefore, highly advisable to
avoid alcohol containing mouthrinses in patients undergoing orthodontic treatment
and use alcohol-free mouthrinses as adjuncts to regular oral hygiene procedures
for maintaining good enamel integrity and periodontal health, without
compromising the shear bond strength of the bonded metal brackets.
PMID- 24355966
TI - A simplified technique for custom made overdenture semi-precision attachments.
AB - CONTEXT: Overdentures are the choice of treatment for most of them, but the only
snag is its cost. In India, the rural areas are still deprived of quality
treatment. This manuscript is showcasing a study, which is a cheaper, but
effective way to provide the best to the patient. AIMS: The aim of this study was
to develop a custom made system, which can be used as an alternative treatment
for the management of patients who need overdentures. The primary objective of
this study was to provide a cost-effective attachment with the best functional
efficacy. MATERIALS AND METHODS: The semi-precision attachments were made by
using the conventional technique of preparation of post space. The patterns were
prepared by using the pattern resin material and the rest of the male and female
attachments were fabricated by using innovative methods fulfilling the criteria.
RESULTS: The attachments were successfully used in patients with remarkably good
function and comfort. CONCLUSION: It was a successful attempt to provide the
specialized treatment in affordable cost. There is a need of innovative work to
make the sophisticated systems more economical and readily available.
PMID- 24355967
TI - Platelet rich fibrin: a new hope for regeneration in aggressive periodontitis
patients: report of two cases.
AB - The purpose of this study was to evaluate the effectiveness of platelet rich
fibrin (PRF) in periodontal regeneration in generalized aggressive periodontitis
(GAgP) patients. Two patients diagnosed with GAgP were selected for this study.
Baseline clinical and radiographic examination was performed and patients were
treated by surgical periodontal therapy along with PRF. Post-surgical re
evaluation was carried out at regular intervals to evaluate clinical and
radiographic changes. Surgical periodontal therapy accompanying the placement of
PRF in angular defects of GAgP patients showed decreased probing pocket depth,
increased attachment level and radiographic bone fill when baseline and 9 month
follow-up data was compared. Surgical reconstructive therapy with placement of
PRF in angular defects of GAgP patients can be an effective approach to enhance
the periodontal regeneration.
PMID- 24355969
TI - Benign fibrous histiocytoma of the tongue.
AB - Benign fibrous histiocytoma (BFH) is a benign fibrohistiocytic neoplasm. It is
documented to occur in all anatomic sites with a strong predilection for sun
exposed skin surfaces. Intra oral occurrence of BFH comprises a lesser percentage
of cases with tongue being the least reported site. We report a case of BFH of
the tongue with an emphasis on its histogenesis and a review of the literature.
PMID- 24355968
TI - A guise of osteosarcoma: chondroblastoma-like.
AB - Osteosarcoma (OS) is a rare tumor arising from immature bone forming cells or
through neoplastic differentiation of other immature mesenchymal cells into
osteoblasts. Chondroblastoma-like OS is one of the rare forms of OS to be seen in
jaw bones. Aggressive clinical behavior, osteolytic areas in the radiograph and
histological presentation of chondroblastoma such as cells with grooved nuclei,
typical chicken-wire calcification along with areas of tumor osteoid, implied the
diagnosis as chondroblastoma-like OS. Use of reticulin stain further confirmed
the diagnosis. A case of chondroblastoma-like OS is reported, emphasizing the
importance of early diagnosis of aggressive jaw lesions with the help of routine
radiography, histopathology, and special stains.
PMID- 24355970
TI - Alternaria alternata infection associated osteomyelitis of maxilla: a rare
disease entity.
AB - Alternaria alternata is one of the rarest fungi associated with paranasal
sinusitis. Alternaria species are pigmented (also known as dematiaceous or
phaeoid) filamentous fungi, which are well-known soil saprophytes and plant
pathogens that infrequently cause infection in humans mainly, cutaneous lesions.
We present a case of osteomyelitis of maxilla caused by a rare fungus- A.
alternata in a diabetic patient with poor glycemic control who was successfully
treated with antifungal and surgical debridement over the period of 6 months.
PMID- 24355971
TI - Characterization of different verrucous mucosal lesions.
AB - Oral lesions indicative of biopsy represent unique presentation either in the
form of proliferations/ulcerations of the squamous lining epithelium. These
lesions have similar appearance clinically and histopathologically hence are
excised for microscopic evaluation to rule out early or hidden malignancy.
Verrucous mucosal lesions clinically present a diagnostic dilemma, which makes
histopathological examination a significant one in the differentiation of the
lesion to ascertain the nature. This short communication aims to discuss the
different histological characterization of oral verrucous mucosal lesions.
PMID- 24355972
TI - Clinical and genetic aspects of generalized aggressive periodontitis in families
of Tumkur district of Karnataka, India.
AB - BACKGROUND: Aggressive periodontitis (AP) is a complex disease whose phenotype is
determined by genetic and environmental influences on the affected individuals.
About 45% of the adult population in India has periodontitis. In Tumkur district
of Karnataka, India, consanguineous first cousin and uncle-niece marriages are
common, with a high incidence of AP. These discrepancies in the expression of
periodontal disease directed us to find genetic etiology with respect to the
Tumkur population. The clinical and genetic aspects of AP from this area have
been presented in this paper. MATERIALS AND METHODS: A total of nine families
were ascertained at the Department of Periodontics, Sri Siddhartha Dental College
and Hospital (Sri Siddhartha University), Tumkur. The clinical and radiographic
data were gathered according to 1999 Consensus Classification of Periodontal
Diseases. Peripheral blood samples were collected for total genomic DNA isolation
using a Wizard TM Genomic Purification Kit (Promega, USA). The homozygosity
mapping was carried out in a large consanguineous family to map a novel locus
using autosomal markers from the CHLC/Weber Human Screening Set 10 (Research
Genetics Inc., USA) at Indian Institute of Sciences, Bangalore. RESULTS: The
pedigree analysis suggested that the disorder is segregating as an autosomal
trait. The homozygosity mapping failed to identify a locus for generalized AP in
the family. CONCLUSION: The disorder may not be segregating as an autosomal
recessive trait and we could have been misled by consanguinity in the family. It
could be a multifactorial trait, or it could be still segregating as an autosomal
recessive trait, but the region of homozygosity could be small and we failed to
detect it using microsatellite markers. Therefore, SNP-marker-based analysis is
warranted in future.
PMID- 24355973
TI - An in vitro study on effect of Delmopinol application on Candida albicans
adherence on heat cured denture base acrylic resin: a thorough study.
AB - BACKGROUND: Denture-related stomatitis is probably the most common form of oral
candidiasis and its reported prevalence varies widely ranging up to 65%. In this
thorough study, we evaluate the effect of Delmopinol application on Candida
albicans adherence on heat cured denture base acrylic resin. MATERIALS AND
METHODS: A total of 40 specimens of heat-cured acrylic resin were made, 20
specimens were contaminated before Delmopinol treatment and 20 specimens were
contaminated after Delmopinol treatment. The each specimen in each tube was
individually transferred to a spectrophotometer at 530 nm wavelength in order to
measure the turbidity degree, through the transmittance. Aliquots of 10 MUL of
each tube was then collected and inoculated into agar sabouraud plates containing
500 mMol/L of sucrose, which was incubated for 24 hours at 37 degrees C, in order
to check microbial growth. RESULTS: Mean of the turbidity Degree of contamination
after Delmopinol application (1440.80, colony-forming unit [CFU] [*10 6 /ml]) was
significantly higher than the mean of the turbidity degree of contamination
before Delmopinol application (550.85 CFU [*10 6 /ml]). CONCLUSION: Heat-cured
acrylic resin shows greater reduction in adherence of Candida albicans by
contamination after Delmopinol application as compared with contamination before
Delmopinol application.
PMID- 24355974
TI - Filed and granted Indian Patents in dentistry from 2005-2009: a critical analysis
and review.
AB - BACKGROUND: Patent policies have proved to be extremely important for several
countries to develop. India has achieved its global status since 2005; a critical
analysis of the patents at IPO will help us to identify the potential, available
for patents with Indian Dental Fraternity. AIM: The aim of this study is to
critically analyze and review Indian Patents in the field of Dentistry from 2005
2009 for evaluation of status of Indian Patents in Dentistry. MATERIALS AND
METHODS: A total of 110 patents were scrutinized from 2005-2009 available by IPO
on www.patentoffice.nic.in. Following which a preliminary data were collected
from individual patents and recorded in a record sheet. STATISTICAL ANALYSIS: The
data collected were analyzed using SPSS 16.0 software and were subjected to ANOVA
test. RESULTS: All patents scrutinized were applied for dental materials (100%).
Company applicants (70%) were the maximum followed by the individual applicants
(27.2%). A total of 87.3% of patents had enrolled for International Application.
Priority country had maximum favor with USA (39.2%) followed by Europe (36.1%).
Single inventors (44.5%) were the maximum followed by two inventors (22.7%).
Europe (37.3%) had the maximum first inventor, followed by United States of
America (30%) and India (10.9%). Individual inventors were maximum in Europe
(38.8%) followed by USA (20.4%) and India (16.3%). CONCLUSION: Contribution from
Indian Nationals as inventors for patents in the field of Dentistry is limited,
thus reducing the pace of progress and development. Indian inventors in the field
of Dentistry have to go a long way to compete with the fellow mates of developed
countries like USA and Europe. Continuing Dental Education programs on
Intellectual property rights should be conducted on regular basis especially for
Dentist's involved in research.
PMID- 24355975
TI - Limited positron emission tomography-computed tomography for restaging of
lymphoma: a strategy for reducing radiation exposure among patients with early
stage curable lymphoma.
AB - Repeated imaging with positron emission tomography-computed tomography (PET-CT)
is associated with cumulative exposure to substantial doses of radiation.
Furthermore, PET-CT is an expensive and limited resource in many institutions. We
conducted a retrospective analysis to evaluate whether limited PET-CT focused on
the initially involved field of view (FOV) at diagnosis, corresponding to an
above- or below-the-diaphragm scan, is sufficient for follow-up of patients with
Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL). One hundred thirty-one
examinations of 44 patients with early-stage (I-II) HL (n = 27) and aggressive
NHL (n = 17) who had PET-CT performed as part of their initial staging and at
follow-up were analyzed. Regardless of the extent of response to treatment, there
was no single case in which the disease progressed outside of the initially
involved FOV (0/44, 95% CI 0-0.08). This was true even in cases of disease
progression, including in the setting of relapse. Our findings suggest that
limited PET-CT analysis of the initially involved FOV in patients with early
stage curable lymphoma may be satisfactory for response assessment.
PMID- 24355976
TI - Perfusion disturbances of kidney graft parenchyma evaluated with contrast
enhanced ultrasonography in the immediate period following kidney
transplantation.
AB - PURPOSE: Graft parenchyma perfusion disturbances (GPPD) in transplanted kidneys
are common in the early postoperative period. Rapid and accurate diagnosis can
guide proper treatment, preventing graft dysfunction. METHODS: One hundred and
eighty patients, who underwent kidney transplantation (KTx), were examined in the
immediate postoperative period using real-time ultrasonography (B-mode) with
color and power Doppler (US-CD/PD) and B-flow ultrasound, as well as with an
additional protocol of contrast-enhanced ultrasonography (CE-US). Regions of GPPD
were localized and measured. The number and size of these areas were compared
between the two acquisition techniques. Follow-up examinations were carried out 6
months postoperatively. RESULTS: CE-US revealed more GPPDs and showed them more
precisely than the B+US-CD/PD/B-flow technique. Moreover, in the CE-US
examination, ischemic foci had statistically significant higher echogenicity in
comparison to normal parenchyma, were larger and better visualized (better
circumscribed) than in B+US-CD/PD/B-flow. CONCLUSION: CE-US allows the
visualization of GPPD caused by occlusion of small arteries. It is a noninvasive,
safe, real-time method, which has many advantages over standard B+US-CD/PD/B-flow
examinations, and we recommend it as a routine diagnostic procedure in the early
postoperative period following KTx.
PMID- 24355977
TI - Antiproliferative and apoptotic effects of indomethacin on human retinoblastoma
cell line Y79 and the involvement of beta-catenin, nuclear factor-kappaB and Akt
signaling pathways.
AB - BACKGROUND: To determine in vitro if indomethacin inhibits proliferation and
induces apoptosis in human retinoblastoma cell line Y79, and to explore possibly
involved signaling pathways. METHODS: The human retinoblastoma cell line Y79 was
cultured with indomethacin at various concentrations (0, 25, 50, 100, 200 and 400
umol/l). The effect of indomethacin on cell proliferation and apoptosis was
examined by the Cell Counting Kit-8 and TUNEL test, respectively. The mRNA level
of survivin, beta-catenin and Bcl-2 was detected by RT-PCR. The protein level of
survivin was measured by ELISA. Western blot was used to analyze beta-catenin,
nuclear factor (NF)-kappaB/p65, phosphorylated Akt (pAkt) and total Akt (tAkt)
expression in cultured cells. RESULTS: Indomethacin treatment inhibits
proliferation (at concentrations from 25 to 400 umol/l) and induces apoptosis (at
concentrations from 100 to 400 umol/l) of human retinoblastoma cell line Y79 in a
dose-dependent manner. RT-PCR showed that the mRNA expression of Bcl-2 (F =
20.497; p < 0.001) and of beta-catenin (F = 14.835; p < 0.001) was significantly
different among the treated groups. Survivin mRNA levels remained steady, but its
protein levels decreased significantly as measured by ELISA (F = 67.633; p <
0.001). Western blot analysis showed a dose-dependent downregulation of beta
catenin (F = 37.411; p < 0.001), NF-kappaB/p65 (F = 16.302; p < 0.001) and of
pAkt (F = 27.700; p < 0.001) after indomethacin treatment, while tAkt protein
expression was steady among the groups. CONCLUSIONS: Treatment with indomethacin
can potently suppress proliferation and induce apoptosis in the retinoblastoma
Y79 cell line. Wnt/beta-catenin, NF-kappaB and Akt/PKB pathways might be
implicated in the process.
PMID- 24355978
TI - Decision support from local data: creating adaptive order menus from past
clinician behavior.
AB - OBJECTIVE: Reducing care variability through guidelines has significantly
benefited patients. Nonetheless, guideline-based Clinical Decision Support (CDS)
systems are not widely implemented or used, are frequently out-of-date, and
cannot address complex care for which guidelines do not exist. Here, we develop
and evaluate a complementary approach - using Bayesian Network (BN) learning to
generate adaptive, context-specific treatment menus based on local order-entry
data. These menus can be used as a draft for expert review, in order to minimize
development time for local decision support content. This is in keeping with the
vision outlined in the US Health Information Technology Strategic Plan, which
describes a healthcare system that learns from itself. MATERIALS AND METHODS: We
used the Greedy Equivalence Search algorithm to learn four 50-node domain
specific BNs from 11,344 encounters: abdominal pain in the emergency department,
inpatient pregnancy, hypertension in the Urgent Visit Clinic, and altered mental
state in the intensive care unit. We developed a system to produce situation
specific, rank-ordered treatment menus from these networks. We evaluated this
system with a hospital-simulation methodology and computed Area Under the
Receiver-Operator Curve (AUC) and average menu position at time of selection. We
also compared this system with a similar association-rule-mining approach.
RESULTS: A short order menu on average contained the next order (weighted average
length 3.91-5.83 items). Overall predictive ability was good: average AUC above
0.9 for 25% of order types and overall average AUC .714-.844 (depending on
domain). However, AUC had high variance (.50-.99). Higher AUC correlated with
tighter clusters and more connections in the graphs, indicating importance of
appropriate contextual data. Comparison with an Association Rule Mining approach
showed similar performance for only the most common orders with dramatic
divergence as orders are less frequent. DISCUSSION AND CONCLUSION: This study
demonstrates that local clinical knowledge can be extracted from treatment data
for decision support. This approach is appealing because: it reflects local
standards; it uses data already being captured; and it produces human-readable
treatment-diagnosis networks that could be curated by a human expert to reduce
workload in developing localized CDS content. The BN methodology captured
transitive associations and co-varying relationships, which existing approaches
do not. It also performs better as orders become less frequent and require more
context. This system is a step forward in harnessing local, empirical data to
enhance decision support.
PMID- 24355979
TI - RNA: The (methylation) reader.
PMID- 24355980
TI - Cytoskeleton: Remodelling the FtsZ network.
PMID- 24355987
TI - Cell death: E2Ffects on mitochondria.
PMID- 24355988
TI - Cell intercalation from top to bottom.
AB - Animal development requires a carefully orchestrated cascade of cell fate
specification events and cellular movements. A surprisingly small number of
choreographed cellular behaviours are used repeatedly to shape the animal body
plan. Among these, cell intercalation lengthens or spreads a tissue at the
expense of narrowing along an orthogonal axis. Key steps in the polarization of
both mediolaterally and radially intercalating cells have now been clarified. In
these different contexts, intercalation seems to require a distinct combination
of mechanisms, including adhesive changes that allow cells to rearrange,
cytoskeletal events through which cells exert the forces needed for cell
neighbour exchange, and in some cases the regulation of these processes through
planar cell polarity.
PMID- 24355990
TI - Melanoma associated with the use of melanotan-II.
AB - BACKGROUND: Unlicensed use of melanotan-II (MT-II) to promote skin pigmentation
has become prevalent amongst young people attending fitness centres. We present a
case where the melanocyte stimulation of MT-II in combination with the use of sun
tanning beds coincided with cutaneous melanoma. OBSERVATION: A 20-year-old woman
with Fitzpatrick skin type II was referred to a dermatology clinic. Clinical
examination revealed a suspicious black melanocytic lesion in her left gluteal
region. Furthermore, her skin was universally intensely pigmented. The
melanocytic lesion was excised, and histology confirmed the diagnosis of
melanoma. Three months prior to the excision the patient had conducted a 3- to 4
week course of self-injections with MT-II, intending an augmentation of sunbed
tanning. CONCLUSIONS AND RELEVANCE: This observation brings attention to the
potential risks related to the use of the cyclic alpha-melanocyte-stimulating
hormone analogue MT-II. There are several hazardous aspects of the possible
widespread use of MT-II. As the drug is unlicensed and incompletely tested, the
extent and types of adverse effects are unknown. Clinicians are advised to be
aware of the problem, and counsel their at-risk patients regarding the potential
hazards related to the use of MT-II.
PMID- 24355991
TI - Detection of structural abnormalities in the first trimester using ultrasound.
AB - During the past 25 years, embryonic and early fetal ultrasound and diagnosis have
increasingly gained attention in pregnancy care. Modern high-frequency ultrasound
transducers make it possible to obtain detailed images of the early conceptus and
its organs, and thus move part of the anatomy and anomaly scan from the second to
the first trimester. Today, detection of embryonic and fetal structural
abnormalities in the first trimester has frequently been reported. One has to
distinguish between diagnosis during the early period until about 10 weeks when
the embryo or early fetus is small and transvaginal ultrasound is applied, and
diagnosis during the late period at the nuchal translucency screening, usually
carried out using transabdominal ultrasound. Early first-trimester abnormalities
are often diagnosed by chance on clinical indications, whereas late first
trimester diagnoses are the result of systematic screening using ultrasound
markers.
PMID- 24355992
TI - Early pregnancy assessment in multiple pregnancies.
AB - Early ultrasound assessment and accurate determination of chorionicity is crucial
so that appropriate care of multiple pregnancy can be provided. It is best
achieved in the first trimester of pregnancy using the Lambda 'lambda' and 'T'
signs. Accurate labelling of the twins is needed to ensure that the same
individual fetus is measured through the pregnancy so that the longitudinal
growth pattern can be correctly assessed. Discrepancy in crown-rump length
indicates a possibility for future development of selective intrauterine growth
restriction. Careful early ultrasound assessment is needed to identify structural
and chromosomal anomalies, as twin pregnancies are at increased risk. Twin-to
twin transfusion syndrome, selective intrauterine growth restriction and
congenital abnormalities represent the major determinants of perinatal loss in
monochorionic pregnancies, and diagnosis and prognosis are discussed in detail.
Treatment of twin reverse arterial perfusion sequence is more effective in early
pregnancy, so early identification is needed. Outcome of conjoined twins is
guarded, and is dependent on the extent of fusion, degree of sharing of organs,
associated anomalies, and presence of cardiac failure in utero.
PMID- 24355993
TI - Exercise interventions, gait, and balance in older subjects with distal symmetric
polyneuropathy: a three-group randomized clinical trial.
AB - OBJECTIVE: Older patients with a distal symmetric polyneuropathy are at markedly
increase risk for falls and fall-related injuries. Despite this, few studies have
investigated the effect of exercise regimens on gait and balance in this high
risk group. DESIGN: One hundred older patients with distal symmetric
polyneuropathy were randomized to one of three interventions: functional balance
training, Tai Chi, or education-only control. The subjects in each group received
instruction in ten 1-hr weekly sessions. Outcome measures were determined at
baseline and the end of the 10-wk intervention. Gait, balance, and falls self
efficacy were assessed with various well established clinical (Berg Balance
Scale, 8 Foot Up and Go Test, and Modified Falls Efficacy Scale) and laboratory
based measures (three-dimensional gait analysis and NeuroCom limits of stability
and sensory organization tests). RESULTS: The Tai Chi subjects demonstrated a
decreased (faster) Timed Up and Go and increased stride length and time spent in
single limb support at the end of intervention as compared with baseline. The
functional balance training group demonstrated a significant increase in ankle
plantar flexor power and near significant decreases in step width and step width
variability. No changes in the education-only control group were observed.
CONCLUSIONS: Older patients with distal symmetric polyneuropathy may benefit from
Tai Chi and/or functional balance training, with the former improving functional
mobility and gait and the latter possibly improving trunk stabilization and
forward progression (Lythgo N, Cofre LE: Relationship between ankle plantar
flexor power and EMG muscle activity during gait. 30th Annual Conference of
Biomechanics in Sports [Melbourne, 2012]. Available at: https://ojs.ub.uni
konstanz.de/cap/article/viewFile/5320/4891). Whether these laudable changes can
be maintained or translate into decreased risk for falls and fall-related
injuries is unknown.
PMID- 24355989
TI - Control of apoptosis by the BCL-2 protein family: implications for physiology and
therapy.
AB - The BCL-2 protein family determines the commitment of cells to apoptosis, an
ancient cell suicide programme that is essential for development, tissue
homeostasis and immunity. Too little apoptosis can promote cancer and autoimmune
diseases; too much apoptosis can augment ischaemic conditions and drive
neurodegeneration. We discuss the biochemical, structural and genetic studies
that have clarified how the interplay between members of the BCL-2 family on
mitochondria sets the apoptotic threshold. These mechanistic insights into the
functions of the BCL-2 family are illuminating the physiological control of
apoptosis, the pathological consequences of its dysregulation and the promising
search for novel cancer therapies that target the BCL-2 family.
PMID- 24355994
TI - Peripheral nerve stimulation compared with usual care for pain relief of
hemiplegic shoulder pain: a randomized controlled trial.
AB - OBJECTIVE: This study sought to establish the efficacy of single-lead, 3-wk
peripheral nerve stimulation (PNS) therapy for pain reduction in stroke survivors
with chronic hemiplegic shoulder pain. DESIGN: This study is a single-site,
pilot, randomized controlled trial of adults with chronic shoulder pain after
stroke. Participants were randomized to receive a 3-wk treatment of single-lead
PNS or usual care. The primary outcome was the worst pain in the last week (Brief
Pain Inventory, Short Form, question 3) measured at baseline and weeks 1, 4, 12,
and 16. The secondary outcomes included pain interference (Brief Pain Inventory,
Short Form, question 9), pain measured by the ShoulderQ Visual Graphic Rating
Scales, and health-related quality-of-life (Short-Form 36 version 2). RESULTS:
Twenty-five participants were recruited, 13 to PNS and 12 to usual care. There
was a significantly greater reduction in pain for the PNS group compared with the
controls, with significant differences at 6 and 12 wks after treatment. Both PNS
and usual care were associated with significant improvements in pain interference
and physical health-related quality-of-life. CONCLUSIONS: Short-term PNS is a
safe and efficacious treatment of shoulder pain. Pain reduction is greater
compared with usual care and is maintained for at least 12 wks after treatment.
PMID- 24355995
TI - Effects of resistance training and aerobic training on ambulation in chronic
stroke.
AB - OBJECTIVE: The aim of this study was to directly compare the effects of aerobic
training (AT) with progressive resistance training (RT) after stroke to determine
whether AT-induced fitness gains or RT-induced strength gains translate into
improved ambulation across a 12-wk intervention and whether gains are retained 1
yr after cessation of formal training. DESIGN: This study is a randomized
controlled 12-wk intervention trial with a 1-yr follow-up. Forty-three community
dwelling independent walkers with a chronic ischemic hemiparetic stroke were
allocated to AT using a cycle ergometer (n = 13), RT using training machines (n =
14), or low-intensity sham training of the arms (n = 16). The main outcome
measures were 6-min walk distance and fast 10-m walking speed. RESULTS:
Comparisons between AT, RT, and sham training revealed no clinically relevant
effects on walking velocity or walking distance. Muscle strength improved after
RT (P < 0.0001) and was preserved at 1-yr follow-up (P < 0.001). Aerobic capacity
increased after AT (P < 0.001) but was lost during the follow-up observation
period. CONCLUSIONS: Improvement of muscle strength or aerobic capacity using non
task-specific training methods does not result in improved ambulation in patients
with chronic stroke. Muscle strength gains were maintained at follow-up, whereas
all improvements of aerobic capacity were lost, indicating a long-lasting effect
of intensive RT even without maintenance training.
PMID- 24355996
TI - Computerized dynamic posturography: the influence of platform stability on
postural control.
AB - OBJECTIVE: Postural stability can be quantified using posturography systems,
which allow different foot platform stability settings to be selected. It is
unclear, however, how platform stability and postural control are mathematically
correlated. DESIGN: Twenty subjects performed tests on the Biodex Stability
System at all 13 stability levels. Overall stability index, medial-lateral
stability index, and anterior-posterior stability index scores were calculated,
and data were analyzed using analysis of variance and linear regression analysis.
RESULTS: A decrease in platform stability from the static level to the second
least stable level was associated with a linear decrease in postural control. The
overall stability index scores were 1.5 +/- 0.8 degrees (static), 2.2 +/- 0.9
degrees (level 8), and 3.6 +/- 1.7 degrees (level 2). The slope of the regression
lines was 0.17 for the men and 0.10 for the women. CONCLUSIONS: A linear
correlation was demonstrated between platform stability and postural control. The
influence of stability levels seems to be almost twice as high in men as in
women.
PMID- 24355997
TI - Development and psychometric assessment of the function-neutral health-related
quality of life measure.
AB - OBJECTIVE: The aim of this study was to determine the conceptual framework, item
pool, and psychometric properties of a new function-neutral measure of health
related quality-of-life (HRQOL). DESIGN: This is an expert panel review of
existing measures of HRQOL and development of a conceptual model, core
constructs, and item pool and a validation by experts in specific disabilities
and in cultural competence. Items were cognitively tested, pilot tested for
functional bias, field tested with a national sample of adults with various
limitations, and reliability tested via repeat administration. Final item
selection was based on analyses of factor structure, demographic bias, variance
in likelihood of endorsement, and item-total correlation. Psychometric properties
were demonstrated through differential item functioning analyses, factor
analyses, correlations, and item response theory analyses. RESULTS: The results
supported a four-domain conceptual model of HRQOL (physical health, mental
health, social health, and life satisfaction and beliefs) for a 42-item HRQOL
measure with an ancillary 15-item environment scale. The measure has strong
internal consistency (alpha = 0.88-0.97), known-groups validity, and test-retest
reliability (r = 0.83-0.91). Tests of convergent and divergent validity confirmed
the ability of the Function-Neutral Health-Related Quality of Life to measure
health while being relatively free of content assessing function. CONCLUSIONS: A
conceptually grounded four-domain, function-neutral measure of HRQOL that is
appropriate for use with persons with and without various functional limitations
was developed.
PMID- 24355998
TI - The authors respond.
PMID- 24355999
TI - Trends in stroke treatment and outcome between 1995 and 2010: observations from
Riks-Stroke, the Swedish stroke register.
AB - BACKGROUND: Continuous changes in stroke treatment and care, as well as changes
in stroke characteristics, may alter stroke outcome over time. The aim of this
paper is to describe time trends for treatment and outcome data, and to discuss
if any such changes could be attributed to quality changes in stroke care.
METHODS: Data from Riks-Stroke, the Swedish stroke register, were analyzed for
the time period of 1995 through 2010. The total number of patients included was
320,181. The following parameters were included: use of computed tomography (CT),
stroke unit care, thrombolysis, medication before and after the stroke, length of
stay in hospital, and discharge destination. Three months after stroke, data
regarding walking, toileting and dressing ability, as well social situation, were
gathered. Survival status after 7, 27 and 90 days was registered. RESULTS: In
1995, 53.9% of stroke patients were treated in stroke units. In 2010 this
proportion had increased to 87.5%. Fewer patients were discharged to geriatric or
rehabilitation departments in later years (23.6% in 2001 compared with 13.4% in
2010), but more were discharged directly home (44.2 vs. 52.4%) or home with home
rehabilitation (0 vs. 10.7%). The need for home help service increased from 18.2%
in 1995 to 22.1% in 2010. Regarding prevention, more patients were on warfarin,
antihypertensives and statins both before and after the stroke. The functional
outcome measures after 3 months did improve from 2001 to 2010. In 2001, 83.8% of
patients were walking independently, while 85.6% were independent in 2010. For
toileting, independence increased from 81.2 to 84.1%, and for dressing from 78.0
to 80.4%. Case fatality (CF) rates after 3 months increased from 18.7% (2001) to
20.0% (2010). This trend is driven by patients with severe strokes. CONCLUSIONS:
Stroke outcomes may change over a relatively short time period. In some ways, the
quality of care has improved. More stroke patients have CT, more patients are
treated in stroke units and more have secondary prevention. Patients with milder
strokes may have benefited more from these measures than patients with severe
strokes. Increased CF rates for patients with severe stroke may be caused by
shorter hospital stays, shorter in-hospital rehabilitation periods and lack of
suitable care after discharge from hospital.
PMID- 24356000
TI - Free radicals: how do we stand them? Anaerobic and aerobic free radical (chain)
reactions involved in the use of fluorogenic probes and in biological systems.
AB - Biologically significant conclusions have been based on the use of fluorogenic
and luminogenic probes for the detection of reactive species. The basic
mechanisms of the processes involved have not been satisfactorily elucidated. In
the present work, the mechanism of the enzyme and photosensitized oxidation of
NAD(P)H by resorufin is analyzed and appears to involve both aerobic and
anaerobic free radical chain reactions. There are two major fallouts of this
analysis. Many of the conclusions about the participation of radicals based on
the use of probes such as resorufin and Amplex red need reevaluation. It is also
concluded that anaerobic free radical reactions may be biologically significant,
and the possible existence of enzymatic systems to eliminate certain free
radicals is discussed.
PMID- 24356001
TI - miR-375 inhibits proliferation of mouse pancreatic progenitor cells by targeting
YAP1.
AB - BACKGROUND/AIMS: The Hippo signaling pathway regulates expansion and
differentiation of stem cells and tissue progenitor cells during organ
development and tissue regeneration. Previous studies have shown that YAP1, a
potent effector of the Hippo signaling pathway, plays a crucial role in pancreas
development, but the function of YAP1 in pancreatic progenitor cells is less
known. METHODS: The spatio-temporal expression pattern of YAP1 in mouse
developing pancreata was detected by in situ hybridization. The effect of
silencing YAP1 on the proliferation of pancreatic progenitor cells was analyzed
by CCK-8 assay and Ki67 immunostaining. The regulation of miR-375 on YAP1
expression was determined by dual luciferase reporter assay, QRT-PCR and western
blot. Finally, the influence of miR-375 on proliferation of pancreatic progenitor
cells was analyzed by CCK-8 assay and Ki67 immunostaining. RESULTS: We found that
YAP1 was highly expressed in embryonic and adult pancreatic progenitor cells.
Knocking down YAP1 by siRNA inhibited the proliferation of pancreatic progenitor
cells. The mouse YAP1 was a target gene of miR-375, and miR-375 could target the
3' UTR of YAP1 mRNA to decrease its protein and mRNA levels. Similar to silencing
YAP1 by siRNA, the proliferation of pancreatic progenitor cells was inhibited
significantly by miR-375. CONCLUSION: Our results indicate that YAP1 is necessary
for the proliferation of pancreatic progenitor cells and miR-375 participates in
regulating YAP1 expression during pancreatic progenitor cells differentiation.
PMID- 24356002
TI - Complex and strongly anisotropic magnetism in the pure spin system EuRh2Si2.
AB - In divalent Eu systems, the 4f local moment has a pure spin state J = S = 7/2.
Although the absence of orbital moment precludes crystal electric field effects,
we report a sizable magnetic anisotropy in single crystals of EuRh2Si2. We
observed a surprisingly complex magnetic behavior with three successive phase
transitions. The Eu(2+) moments order in a probably amplitude-modulated structure
below 24.5 K, undergoing a further transition to a structure that is possibly of
the equal-moment type, and a first order transition at lower temperatures,
presumably into a spin spiral structure. The sharp metamagnetic transition
observed at low fields applied perpendicular to the hard axis is consistent with
a change from a spiral to a fan structure. These magnetic structures are
presumably formed by ferromagnetic planes perpendicular to the c axis, stacked
antiferromagnetically along c but not of type I, at least just below the ordering
temperature. Since EuRh2Si2 is isoelectronic and isostructural to EuFe2As2 at
room temperature, our results are also relevant for the complex Eu-magnetism
observed there, especially for the transition from an antiferromagnetic to a
ferromagnetic state observed in EuFe2P2 upon substituting As by P.
PMID- 24356004
TI - Chilly mice confound cancer studies.
PMID- 24356005
TI - Fruit flies in space.
PMID- 24356007
TI - Male reproduction contribution down to two genes.
PMID- 24356008
TI - Copper promotes tumor growth.
PMID- 24356010
TI - 64th AALAS National Meeting.
PMID- 24356011
TI - Venomous but not villainous.
PMID- 24356012
TI - Response to protocol review scenario: right info, wrong place.
PMID- 24356013
TI - Changing a protocol form to list animal number by strain.
PMID- 24356014
TI - Response to protocol review scenario: when strain matters.
PMID- 24356015
TI - Response to protocol review scenario: change to ensure compliance.
PMID- 24356016
TI - All the information on animal lab accreditation.
PMID- 24356017
TI - An erythematous mass on the lip of a guinea pig (Cavia porcellus).
PMID- 24356018
TI - Short-term variability in biomarkers of bone metabolism in sheep.
AB - Changes in bone remodeling during pathological states and during their treatment
can be assessed noninvasively by measuring biomarkers of bone metabolism. Their
application is limited, however, by the potential biological variability in the
levels of these biomarkers over time. To determine the short-term variability in
biomarkers of bone metabolism in adult sheep, the authors measured serum levels
of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP),
osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP),
deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and
phosphorus intermittently over a 12-week period. There were significant
differences in mean ALP activity and in phosphorus concentrations over time, but
all other biomarkers showed no significant short-term variability. The results
suggest that biomarkers of bone metabolism in sheep, especially the bone
resorption marker DPD and the bone formation marker BALP, can be used reliably to
detect changes in bone cellular activity.
PMID- 24356019
TI - Building the human component into contingency plans.
AB - In the 'who, what, when, where and how' approach to disaster and contingency
planning, the 'who' component often receives less attention than it should. It is
relatively easy to determine the appropriate amounts of feed and bedding to store
for emergencies or how to stage a replacement generator for electricity, whereas
planning for the people who will respond to the emergency is more difficult.
Understanding the issues involving 'who' designs and implements the contingency
plan for disaster response can help facility managers to build a more effective
plan, ultimately ensuring faster recovery and long-term success.
PMID- 24356020
TI - Teaching technicians about animal research.
PMID- 24356021
TI - Dollars and demographics.
PMID- 24356022
TI - Taking the pain away.
PMID- 24356023
TI - Infant crying, colic, and gastrointestinal discomfort in early childhood: a
review of the evidence and most plausible mechanisms.
PMID- 24356037
TI - Metabolic syndrome and chronic kidney disease as risk factors of osteoporosis.
AB - AIMS: Osteoporosis is a significant cause of morbidity and mortality, and is
often accompanied by metabolic syndrome (MetS) and chronic kidney disease (CKD).
We demonstrated the relationship among MetS, CKD and osteoporosis, and
investigated the roles of MetS and CKD in the occurrence of osteoporosis in a
healthy Korean population. METHODS: The estimated glomerular filtration rate
(eGFR) was calculated using the modification of diet in renal disease study
equation. The diagnosis of MetS was made according to the updated guidelines from
the American Heart Association/ National Heart, Lung, and Blood Institute. Bone
mineral density (BMD) values were measured. A decreased BMD level was defined as
either osteopenia or osteoporosis. RESULTS: The subjects comprised 38.9% men and
61.1% women; 6.6% had CKD, 19.4% had MetS, and 12.2% had osteoporosis. In
females, the prevalence of MetS and CKD was higher in those with decreased BMD (p
= 0.034 and p = 0.114, respectively). The risks for decreased BMD increased with
fewer MetS components and lower eGFR in a simple logistic analysis. However, the
correlation disappeared when adjusted for age. In males, the prevalence of MetS
and CKD was lower in decreased BMD (p = 0.034 and p = 0.157, respectively). Both
the presence of MetS components and lower eGFR had protective effects on BMD
values in simple and multiple logistic analyses. CONCLUSIONS: In females,
decreased BMD was positively related with both MetS and CKD. But, this
relationship was not seen by adjustment for age. In males, lower BMD was
negatively related to both MetS and CKD in unadjusted and adjusted models.
PMID- 24356038
TI - Relationship between heart rate variability and pulse wave velocity and their
association with patient outcomes in chronic kidney disease.
AB - BACKGROUND: Arterial stiffness and low heart rate variability (HRV) have each
been associated with increased cardiovascular risk in a variety of patient
populations. We explored the relationship between HRV and pulse wave velocity
(PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD
prior to ESRD) along with examining their association with the outcomes of
cardiovascular disease (CVD), death, and progression to end stage renal disease
(ESRD). METHODS: The RRI-CKD Study is a 4-center prospective cohort study of CKD
stages 3 - 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and
carotid-femoral PWV (n = 240). Multiple linear regression was used to assess
predictors of PWV and Cox regression to investigate the association of HRV and
PWV with time to first CVD event or death and ESRD. RESULTS: Although several HRV
measures were inversely correlated with PWV, this association was attenuated
after adjustment for age and/or diabetes and no longer significant after
adjustment for C-reactive protein. Low HRV and high PWV were individually
associated with increased risk of the composite endpoint of CVD/death in
multivariable analysis. The risk of the composite of CVD/death was highest for
patients with both low HRV and high PWV. CONCLUSION: Age, diabetes, and
inflammation together explained the inverse association between HRV and PWV.
Inflammation may play a role in the pathogenesis of both low HRV and high PWV.
The combination of low HRV and high PWV showed the strongest association with a
composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and
the role of these measures as intermediate outcomes in future trials in CKD
patients, merit further study.
PMID- 24356039
TI - Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following
"bath salts" injection.
AB - "Bath salts" is a well known street drug which can cause several cardiovascular
and neuropsychiatric symptoms. However, only one case of acute kidney injury has
been reported in the literature. We present a case with sympathomimetic syndrome,
choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury
following the use of bath salts. A 37-year-old man with past medical history of
hypertension and depression was brought to the emergency center with body
shaking. Three days before admission he injected 3 doses of bath salts
intravenously and felt eye pain with blurry vision followed by a metallic taste,
strange smells, profuse sweating, and body shaking. At presentation he had a
sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea,
and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed
leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of
15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for
amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his
ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters
of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved
his symptoms and his renal failure. Bath salts contain 3,4
methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake
inhibitor. Choreoathetosis in this patient could be explained through
dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for
acute kidney injury from bath salts may involve direct drug effects though
norepinephrine and dopamine-induced vasoconstriction (renal ischemia),
rhabdomyolysis, hyperthermia, and/or volume contraction.
PMID- 24356040
TI - Prognostic impact of intratumoral C-reactive protein expression in patients with
clear cell renal cell carcinoma.
AB - BACKGROUND: Elevated serum C-reactive protein (CRP) level has been demonstrated
to predict poorer survival of both localized and metastatic renal cell carcinoma.
However, the prognostic value of intratumoral CRP expression has not been
sufficiently studied. PATIENTS AND METHODS: In the present study, the expression
of CRP was evaluated with immunohistochemical analysis in 127 patients who had
undergone curative surgery for clear cell renal cell carcinoma. CRP staining was
scored using the immunoreactivity score. An immunoreactivity score of 4 (median
value) or lower was considered negative, a score higher than 4 was considered
positive CRP expression. RESULTS: Univariate analysis revealed that Fuhrman
grade, necrosis, vascular invasion, TNM stage and CRP expression were associated
with tumor-specific survival. Multivariate analysis using the Cox proportional
hazards regression method revealed only TNM stage as an independent predictor of
tumor-specific survival (p = 0.001). A trend towards significance (p = 0.066) was
observed with CRP expression, but it did not reach significance. Patients with a
positive CRP score were 3.46 times more likely to die than patients with a
negative CRP score. CONCLUSION: Our results suggest that the assessment of
intratumoral CRP expression may be a useful tool for predicting the prognosis in
patients with clear cell renal cell carcinoma.
PMID- 24356041
TI - Planning for EVAR: the role of modern software.
AB - Endovascular intervention has revolutionized the treatment of aortic disease,
extending the cohort of patients eligible for repair. Accurate planning for
endovascular aortic repair is essential. Recent advances in modern software have
demonstrated potential for improving outcomes and enhancing the decision making
process beyond 3D measurements and intraoperative navigation techniques. With
increasing uptake and complexity of endovascular therapies requiring
multidisciplinary collaborations, it has become apparent that planning must
extend to the preparation of entire interventional teams and support the early
identification and prevention of potentially harmful events. This paper will
examine recent advances not only in morphological planning and computational
modelling, but also the role of software in the preparation of teams and
prevention of error.
PMID- 24356042
TI - Current results of total endovascular repair of thoracoabdominal aortic
aneurysms.
AB - Minimally invasive surgical solutions for patients with extensive aortic disease
are eagerly awaited, since open repair is often associated with high rates of
morbidity and mortality. In the last decade, the development of fenestrated and
branched aortic endografts has offered a therapeutic option to patients deemed
unsuitable for major surgery. Preliminary studies showed promising early results,
while mid- and long- term data are scarce. The aim of this paper was to review
current results of total endovascular repair of thoracoabdominal aortic aneurysms
(TAAA) with a single model of endograft in the published literature. A literature
search was conducted, and our two-center experience with fenestrated and branched
endografts in the treatment of TAAA, with the Cook Zenith endograft, is
presented. Early results show perioperative mortality rates ranging from 0% to
21%, spinal cord ischemia from 0% to 33.3%. At a mean follow up ranging from 9 to
19 months, reinterventions are needed in 3.3% to 25% of the cases, with a mid
term visceral branch patency of 90% to 100%. Current experiences with total
endovascular TAAA repair show promising results, in selected centers with large
experience in complex aortic endografting. With increasing follow- up times, need
for reintervention is growing, while aneurysm-related deaths remain rare. Long
term results are still lacking, but these encouraging data and further
technological developments will support wider adoption of the technique.
PMID- 24356043
TI - Early mid-term results of the first 103 cases of multilayer flow modulator stent
done under indication for use in the management of thoracoabdominal aortic
pathology from the independent global MFM registry.
AB - AIM: We report mid-term results from the Global Independent multilayer flow
modulator (MFM) registry using a uni-modular multilayer flow modulator stent
technology. METHODS: We present the first 103 cases out of the 380 cases
implanted in Europe under indications for use. All were done on a compassionate
basis, in 12 countries, and were fully analyzed through the MFM registry. Primary
endpoints were: one-year freedom from rupture and aneurysm-related death, one
year all cause mortality, patency of visceral branches at one year, and one year
incidence of stroke and paraplegia. Primary technical endpoints were aneurysm sac
volume modulation at one year. Secondary technical endpoints were technical
success and one-year freedom from reintervention. Mean age of 69.2 years (16-93
years), mean aneurysm diameter was 6.4+/-1.66 cm and mean length was 12.96 cm.
They were 75 Crawford thoracoabdominal aortic aneurysms (TAAA) (11 Type I, 14
Type II, 26 Type III, and 24 Type IV), 7 arch aneurysms, 15 suprarenal aortic
aneurysms and 6 type B dissections. The mean number of side branches covered for
a total number of 378 branches is 3.7 side branches per case. Total numbers of
stents used was 176 with a mean of 1.71 MFM stents per case; 77.77 were ASA IV E,
72.7% had previous thoracic endovascular aortic repair or open TAAA repair.
RESULTS: Thirty-day morbidity was 5.4% with zero mortality. Aneurysm related
survival was 91.7% at one year. No rupture occurred. Four cases of consumptive
coagulopathy were observed, two of which resulted in death from hemorrhagic
cerebrovascular stroke and one of which resulted in death from a gastrointestinal
bleed. Technical success was 97.3%. One-year all-cause survival was 86.8%. At 12
months 95.1% of all visceral branches were patent. There were no stent fractures.
One-year intervention free survival was 89.4%. At six months the mean rate of sac
volume increase was 0.57%% per month, resulting in a mean volume increase of
2.56%. At 12 months the rate of increase had slowed to 0.33% per month, resulting
in a total average increase in sac volume of 5.07%. Mean base line thrombus
volume was 297.54 cm3. At one year the mean thrombus volume was 361.38 cm3 with
mean volume change of 63.45 cm3. However, mean base line total volume was 332.79
cm3. At one year the mean total volume was 355.4 cm3 with a mean total volume
change of 22.61 cm3. The mean base line maximum diameter was 6.27 cm. At one year
mean maximum diameter was 7.06 cm with mean total change of 0.79 cm3. The mean
baseline residual flow volume was 71.75 cm3. At one year, mean residual flow
volume had decreased to 63.3cm3 with mean volume change of 8.4 cm3. CONCLUSION:
Increasing sac volume, thrombus or diameter size was not associated with rupture.
MFM implantation instigates a process of aortic remodeling involving initial
thrombus deposition, which slows between six and twelve months. This Global MFM
Registry data has demonstrated the proof of concept of this disruptive
technology.
PMID- 24356044
TI - Ultra-low profile Ovation device: is it the definitive solution for EVAR?
AB - When Juan Parodi implanted an endograft in a human body for the first time on
September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade
device was primitive, extremely rigid, and had a bulky profile of 27 French (F).
Since then, stent-graft technology has evolved rapidly, limitations of earlier
generation devices have been overtaken, and endovascular aneurysm repair (EVAR)
eligibility has increased enormously. Nevertheless (still) challenging aortoiliac
anatomy such as short and complex proximal aortic neck seal zones and narrow
access vessels are responsible for EVAR ineligibility in up to 50% of cases. The
Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA,
USA) is a trimodular device designed with the aortic body delivered via a
flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter -
OD). The aortic body is provided with a suprarenal nitinol stent with anchors
that provide active fixation, while a network of rings and channels that are
inflated with a low-viscosity radiopaque polymer during stent-graft deployment,
provides effective sealing. The previous EVAR technology aimed to both anchor and
seal using stents combined with fabric, with neither optimized for their roles
and each forced to compete for the same space within their delivery catheters,
which inevitably led to larger profile of the delivery system. The technical
revolution of the Ovation endograft includes the idea to truly uncouple the
stages of stent-graft fixation and seal during the procedure. In the Ovation
endograft platform, stent and fabric are not competing the same space within the
delivery system and an ultra-low profile delivery can be achieved without
compromise. With such a low-profile delivery catheter, approximately 90% of men
and 70% of women with abdominal aortic aneurysm have access vessel diameters
considered fit for endovascular repair. The aim of this review paper was to
analyze the main properties of Ovation endograft, to emphasize the advantage of
the ultra-low profile device, and to sum up current literature.
PMID- 24356045
TI - The Gore Excluder AAA endoprosthesis with C3 delivery system: results in high
volume centers.
AB - The use of endovascular aortic aneurysm repair (EVAR) has increased dramatically,
chiefly because of its low perioperative morbidity compared with open surgery.
Challenges to the success of EVAR remain, however, with the most important being
features of the patient's infrarenal aortic neck anatomy that make optimal
placement of the endoprosthesis difficult. These features include a short, wide,
severely angulated, or reverse-tapered neck and the presence of calcifications or
thrombus. Suboptimal endograft positioning may necessitate use of aortic cuffs,
thereby increasing the time and cost of an EVAR procedure, or increase the
likelihood of graft migration, which can lead to endoleaks and additional
interventions. Efforts to improve outcomes of EVAR and expand its application in
patients with challenging aortic neck anatomy have focused on the development of
endografts and delivery systems with innovative designs. The low-permeability
Gore Excluder AAA endoprosthesis with C3 delivery system, which became available
in Europe and the United States in 2010, represents one such design. The C3
system allows the proximal end of the endoprosthesis to be reconstrained after
insertion so that the device can, if necessary, be rotated or moved cranially or
caudally. Repositioning may facilitate contralateral gate cannulation and
placement of the endograft closer to the lowest renal artery (without covering
its orifice), thereby possibly decreasing the risk of inadequate sealing and
consequent graft migration and endoleaks. Early clinical studies of the Gore
Excluder AAA endoprosthesis with C3 delivery system have yielded promising
results.
PMID- 24356046
TI - INCRAFT(r) Stent-Graft System: one-year outcome of the INNOVATION Trial.
AB - AIM: Endovascular repair has surpassed open surgical treatment as the most common
procedure in patients with abdominal aortic aneurysms (AAA), yet its
applicability remains limited to those with aortoiliac anatomy suitable for the
introduction and deployment of the devices. The current study was performed to
assess the safety and efficacy of INCRAFT(r) (Cordis Corporation, Bridgewater,
NJ), an ultra-low-profile device for the treatment of AAA. METHODS: The
INNOVATION study is a first in human prospective, multicenter trial involving 6
centers in Europe. From March 2010 to June 2011 60 patients with asymptomatic AAA
were treated with the INCRAFT(r) bifurcated Stent-Graft System. The main
inclusion criteria were a proximal aortic neck of 15 mm or more in length and up
to 27 mm in diameter; iliac landing zones greater than 10 mm in length and
between 9 and 18 mm in diameter; an access vessel large enough to accept the 14F
outer diameter of the delivery system; and an aortic bifurcation >18 mm in
diameter. The primary endpoint was technical success at one-month; one-year
safety endpoints included the absence of device- or procedure-related major
adverse events; absence of type I or III endoleaks; and maintenance of device
integrity through one year of follow-up. RESULTS: Among 60 patients treated at
six centers, the primary endpoint was met in 56 of 58 patients (97%; 95% CI, 88
100%) who came back for one month follow-up, two patients did not come back for
their one month follow-up assessments but remained enrolled in the study. Fifty
six had one-year follow-up data showing 100% freedom from aneurysm enlargement
with absence of type I and III endoleaks in all patients. There were two patients
(3.6%) with a type Ia endoleak which was successfully treated with secondary
endovascular intervention in both occasions. Core laboratory evaluation of the
postoperative imaging studies documented absence of endograft migration, stent
fracture, or limb occlusion. A single patient (1.8%) died within one year due to
sepsis unrelated to the AAA. CONCLUSION: The results of the INNOVATION study with
the INCRAFT(r) Stent-Graft are encouraging, with satisfactory clinical outcome
and device durability through one-year of follow-up. The INCRAFT(r) device is a
novel ultra-low-profile endograft that holds promise to broaden the patient
population eligible for endovascular aneurysm repair.
PMID- 24356047
TI - AorfixTM device for abdominal aortic aneurysm with challenging anatomy.
AB - Anatomical characteristics of abdominal aortic aneurysms (AAA) are the most
critical factors for successful endovascular aortic repair (EVAR). Of these,
severe proximal aortic neck angulation and iliac axis tortuosity increase the
complexity of EVAR. Neck angulation seems to have a pivotal potential for
fixation failure, a situation that may lead to complications, including endoleak
and late rupture. Bench-test studies identified that the relative stiffness of a
stent-graft was responsible for its inability to conform to neck angulation,
therefore creating leaks through gaps between the stent graft and the neck.
AorfixTM stent graft (Lombard Medical, Didcot, UK) is a flexible stent-graft
designed and manufactured with the purpose of overcoming the issue of stent-graft
stiffness. Many studies have shown good results in term of procedural success and
mid-term type-I endoleak. PYTHAGORAS trial evaluated mainly patients with highly
angulated infrarenal neck and showed that high performance of AorfixTM stent
graft did not present any significant difference between neck >60 degrees and
<60 degrees . In the series of 27 patients treated at our Institution we had a
primary technical success of 96.3% and an assisted primary technical success of
100%. In this review we will analyze the available data in literature regarding
AorfixTM stent graft and will discuss the outcome of the patients treated with
AorfixTM stent graft at our centre.
PMID- 24356048
TI - New possibility of AAA treatment with E-vita abdominal device.
AB - The most dramatic shift in the management of abdominal aortic aneurysms (AAAs)
occurred in 1991, when the first endovascular AAA repair was reported.
Endovascular aneurysm repair has revolutionized the treatment of infrarenal AAAs.
In the last few years, the companies have developed renewed models of grafts and
have modified delivery systems tending to make them more atraumatic and flexible
in order to deal with difficult anatomies and severely atheromatous and tortuous
vessels. The aim of the present paper was to analyze the technical
characteristics and properties of the new stent-graft system E-vita abdominal XT
and to review the current literature. The E-vita abdominal XT stent-graft seems
to be safe and reliable; however, long-term results are needed.
PMID- 24356049
TI - The Bolton Treovance endograft: single center experience.
AB - AIM: In the last two decades, results of endovascular aortic repair (EVAR) for
the treatment of infrarenal abdominal aortic aneurysms (AAAs) have significantly
improved thanks to the evolution of stent-grafts and endovascular delivery
systems. However, further development is still needed to reduce the incidence of
complications and secondary reinterventions. We present our initial experience
with the Treovance abdominal aortic stent-graft (Bolton Medical, Barcelona,
Spain), a new-generation trimodular endovascular device, developed to increase
flexibility, lower profile, improve deployment and sealing mechanisms. METHODS:
We treated 8 patients with anatomically suitable non-ruptured AAA. RESULTS:
Primary technical success was obtained in all patients, and no 30-day device
related complications nor deaths were reported. One patient experienced graft
limb occlusion at 3 months, and underwent surgical conversion. At 1-year follow
up (completed in 6 patients), no device-related complications nor type I or III
endoleak were observed. CONCLUSION: Initial personal experience with the
Treovance abdominal stent-graft was satisfactory with regard to technical success
and short-term clinical results. This new-generation endovascular device
performed well even in angulated or heavily calcified anatomies.
PMID- 24356050
TI - Two-year-results of Endurant stent-graft in challenging aortic neck morphologies
versus standard anatomies.
AB - AIM: The aim of this paper was to evaluate the influence of a challenging neck on
mid-term results using the Endurant I stent-graft system in high risk patients.
METHODS: A retrospective study was conducted on a prospectively compiled database
of 72 elective patients with challenging neck treated with the Endurant I system
(Endurant Stent Graft, Medtronic AVE, Santa Rosa, CA, USA). These patients were
compared to a control group (65 patients) without significant neck problems. The
endpoints were mid-term 2-years technical, clinical success and the event free
survival of all treated patients. RESULTS: Mean age was 76.12 years; 76.6% of
patients were males. Risk factors and preoperative variables did not differ
significantly between the two groups. Only 4 (5.5%) patients of the study group
vs. 2 (3.1%) in the control group developed type I endoleak during the follow-up.
Three (4.1%) study group patients developed type III endoleak vs. 2 (3.1%) in the
control group. All these patients required an adjunct procedure of relining with
a new endograft. No type II endoleaks requiring adjunctive endovascular
procedures were detected in our series. The 2-year event free survival rate did
not differ statistically between the two groups (P=0.425). CONCLUSION: Treatment
with the Endurant stent-graft is technically feasible and safe, yielding
satisfactory results even in challenging anatomies. Mid-term results are
promising and challenge current opinion concerning the negative influence of
challenging neck anatomy on EVAR especially after a longer follow-up.
PMID- 24356051
TI - Novel sealing concept in the Endologix AFX unibody stent-graft.
AB - A major ongoing challenge for the endograft industry has been to create an
endograft that assures the same reliable aneurysm seal afforded by surgical
resection and suturing of a prosthetic graft to the abdominal aortic wall. The
focus of these developmental efforts has always been the proximal neck, where the
endo-graft must be firmly affixed to the aorta to prevent device movement and
seal against leakage. The two mechanisms of fixation and seal, however, apply to
both the proximal and the distal landing zones. Today's bifurcated stent-graft is
configured much as it was two decades ago, with a short main body and long limbs,
one of which must be mated to the main body after its deployment. The unibody
Powerlink endograft made by Endologix, with its long main body and two innate
limbs, is deployed so that it rests on the native aortoiliac bifurcation, the
first and still only bifurcated endograft design to use anatomical fixation for
stabilization and separate seal from fixation. The original Powerlink stent-graft
has several design features that have allowed engineers to evolve new sealing
technology that is featured on the company's latest iteration, the AFX
Endovascular AAA System. This article reviews the approaches taken to enhance the
device's ability to reduce type I endoleaks and provides some insight into the
challenges of creating the perfect seal for an aortic stent-graft.
PMID- 24356052
TI - Rationale of EndoAnchors in abdominal aortic aneurysms with short or angulated
necks.
AB - Diseased pararenal aortic anatomy including thrombus, calcification, and
progressive dilatation, may impact the long-term durability of endovascular
aortic aneurysm repair. EndoAnchors have been shown to mimic the security of a
hand sewn aortic anastomosis. Several investigators have evaluated the use of
EndoAnchors to repair endograft problems or repair type 1 endoleaks in the
abdominal or the thoracic position. The ANCHOR Registry is designed to evaluate
up to 2000 patients at multiple sites in North America and Europe who have been
treated with the Aptus Heli-FX EndoAnchor System to secure an aortic endograft.
The registry collects important clinical characteristics of patients (1000) who
are treated at the initial endograft implant (PRIMARY ARM) due to the presence of
an endoleak or the concern about late failure due to a hostile aortic neck. An
additional 1000 patients, who undergo a secondary procedure for treatment of an
endoleak or other proximal graft failure (e.g., migration, aortic dilatation)
will also be evaluated and followed (REVISION ARM). Currently, more than 290
patients have been entered and will be followed to evaluate the long-term
efficacy of this treatment.
PMID- 24356053
TI - Type II endoleak: a problem to be solved.
AB - Type II endoleak is a common phenomenon after endovascular aortic aneurysm repair
(EVAR). The majority of type II endoleaks are considered benign, since
approximately one third of them resolve spontaneously and they have no influence
on mortality and rupture rate after EVAR. Thus, type II endoleak without sac
expansion is recommended to be observed conservatively. Treatment for type II
endoleak with sac expansion is still controversial. It has been reported that a
certain type II endoleak causes sac expansion and late aneurysm rupture. Type II
endoleak is often treated with solid agents as coils and vascular plugs or with
liquid agents as different glues and thrombin. OnyxTM is a relatively new liquid
embolic agents and it seems promising due to its capability to be injected in
controlled manner with good visualization. Perisac embolization is another novel
technique and it deals with all patent arterial branches, yet it requires further
long-term studies. There are several access routes in treatment for type II
endoleak. Translumbar approach seems more successful and safe than transarterial
approach, and transcaval approach reduces the risk for infection compared to
translumbar embolization. However, success rate of intervention for type II
endoleak is unsatisfactory and recurrence rate is high. Endovascular treatment
for type II endoleak is dependent on its nature and sometimes it can be
challenging. Therefore, treatment for type II endoleak, including preventive
embolization should be considered carefully and development of embolization
methods is essential.
PMID- 24356054
TI - Guidelines on the diagnosis and treatment of extracranial carotid artery stenosis
from the Italian Society for Vascular and Endovascular Surgery.
PMID- 24356055
TI - A new temporal bone and cadaver head holder for temporal bone surgical technique
training.
AB - OBJECTIVE: To design a new temporal bone and cadaver head holder, overcoming the
drawbacks of the bowl-type holder and other existing holders for dissection, and
thereby benefiting training and research on temporal bone surgery. MATERIALS AND
METHODS: We designed and fabricated a novel holder with a horizontal arm that can
be connected with an object holder specific for the temporal bone or a three-pin
fixture specific for cadaver heads. A separate hand support helps to stabilize
the hand during examinations on the temporal bone and skull base. RESULTS: The
use of the temporal bone and cadaver head holder by 30 trainees during our
temporal bone surgical technique courses held by the Department of
Otolaryngology, Peking Union Medical College Hospital (PUMCH) worked better than
other holders and saved laboratory time. It has become the standard equipment of
the Temporal Bone Laboratory of PUMCH. CONCLUSIONS: The temporal bone and cadaver
head holder we describe is compact, stable and easily adjustable. It offers
considerable advantages to trainees.
PMID- 24356056
TI - Romidepsin overcomes cell adhesion-mediated drug resistance in multiple myeloma
cells.
PMID- 24356057
TI - Worsening of Wilson disease following penicillamine therapy.
AB - BACKGROUND: Penicillamine is a standard therapy for Wilson disease (WD) but some
patients have paradoxical worsening. Predictors of such deterioration have not
been evaluated. This study documents frequency and predictors of deterioration
following treatment in WD. METHODS: 59 consecutive patients with neurologic WD
and 4 asymptomatic siblings were prospectively evaluated. Their clinical,
laboratory, ultrasound abdomen and cranial MRI findings with and without
worsening were compared. Patients were treated with oral penicillamine and/or
zinc and followed up at 1, 3 and 6 months or earlier if needed. Deterioration was
defined by >10% worsening in baseline Burke-Fahn-Marsden score or appearance of
new neurological sign. RESULTS: Patients' median age was 13 years and 13 were
females. 19 patients (30.2%) worsened following treatment; 10 within 1 month, 7
in 1-3 months, and 2 after 3 months of treatment. Deterioration was associated
with drooling, leukopenia, thrombocytopenia, splenomegaly and evidence of chronic
liver disease. None of the asymptomatic patients following zinc therapy
deteriorated. CONCLUSIONS: In the deteriorating group, withdrawal of
penicillamine resulted in improvement/stabilization in 11 patients, 2 improved by
trientine therapy and 4 continued to deteriorate till 3 months. 30.2% patients
with WD deteriorated following penicillamine, especially those with chronic liver
disease, leukopenia and thrombocytopenia.
PMID- 24356058
TI - Systematic reviews and meta-analyses in neuroepidemiological research:
applications and issues.
PMID- 24356059
TI - Methodological difficulties in the conduct of neuroepidemiological studies in low
and middle-income countries.
AB - BACKGROUND: The majority of people with epilepsy (PWE) live in low- and middle
income countries (LMICs). However, they remain largely untreated and the bulk of
resources are used to treat patients in the developed world. This disparity
constitutes a challenge for neuroepidemiological studies on a global scale. In
the past, several studies have focused on diverse populations in disparate
countries at various periods of time and for particular purposes. The specificity
of different contexts and circumstances makes it difficult to analyse PWE as a
group either qualitatively or quantitatively. Such methodological limitations are
further complicated by a lack of logistical support. There is a lack of interest
in conducting studies, which results in inadequate funding and, in addition,
there is the considerable challenge of publishing research reports from LMICs in
peer-reviewed international journals. METHODS: This paper focuses on
methodological problems related to studies in LMICs and attempts to give the
reasons for their limitations using epilepsy as an example. RESULTS: Regional
conditions and environmental factors must be given careful consideration in the
research design because of the importance of understanding the challenges of
living in these environments. There are further limitations to the successful
implementation of studies. Existing information on epilepsy is often not readily
accessible; there is a lack of census data, and migratory patterns into cities
make enumeration and sampling even more challenging. As there is usually no well
developed healthcare system a door-to-door screening process is often the only
way to identify those with convulsive epilepsy. The questionnaire and study
design should preferably be adapted from standardized protocols, and pre-tested
and validated in local conditions. CONCLUSIONS: Systematic reviews and meta
analyses of studies in LMICs can provide data on the burden, risk factors,
treatment and outcome of epilepsy only if the primary studies used are properly
conducted using uniform and comparable methodology. The use of consistent
replicable neuroepidemiological methods in primary studies and systematic reviews
enable reduction of the treatment gap and better epilepsy care.
PMID- 24356060
TI - The role of systematic reviews and meta-analyses of incidence and prevalence
studies in neuroepidemiology.
AB - BACKGROUND: Systematic reviews and meta-analyses on the incidence and prevalence
of neurological conditions are important methods of quantifying the burden and
risk of disease. METHODS: The rigorous methodology required in order to minimize
publication bias, account for study heterogeneity, and variation in study quality
are described. When appropriate, a meta-analysis is a powerful statistical tool
that can help synthesize a vast literature quantitatively, taking into account
study heterogeneity. As the epidemiology of neurological conditions continue to
be widely studied internationally, systematic reviews and meta-analyses have
become essential. RESULTS: If not conducted carefully, systematic reviews and
meta-analyses in neuroepidemiology may lead to erroneous conclusions. It is
important to consider various methodological, clinical and statistical factors at
all stages of the review and analysis process. Detailed documentation should be
kept to assist in the reporting process. CONCLUSIONS: Published reporting
standards should be consulted when conducting systematic reviews and meta
analyses of the incidence and prevalence of neurological conditions, though
reporting standards specific to neuroepidemiology are urgently needed.
PMID- 24356061
TI - Vitamin A and carotenoids and the risk of Parkinson's disease: a systematic
review and meta-analysis.
AB - BACKGROUND: Vitamin A and carotenoids are involved in signalling pathways
regulating gene expression in many organs, including the brain. The dopaminergic
system is a target of retinoic acid action in the central nervous system. The aim
of this review is to assess the epidemiological evidence on the association
between blood levels or dietary intakes of vitamin A and carotenoids and risk of
Parkinson's disease (PD). METHODS: PubMed and ISI Web of Science were searched
for relevant papers from 1990 to April 2013. Data reported in epidemiological
studies assessing the association between vitamin A and/or carotenoids (alpha
carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, zeaxanthin and
canthaxanthin) and PD were extracted for a narrative synthesis and meta-analysis.
RESULTS: Thirteen papers were included out of a total of 362 potentially
relevant; of these, eight contributed to the meta-analysis. No statistically
significant pooled estimate between micronutrient and PD was detected. Forest
plots suggest possible non-significant inverse pooled estimates of alpha-carotene
and beta-carotene and risk of PD. A significant association between lutein intake
and PD risk was detected in case-control studies only. CONCLUSIONS: Data
published to date are insufficient for drawing definite conclusions about the
epidemiological evidence on the association between blood levels or dietary
intakes of vitamin A and carotenoids and the risk of PD. Results should be
interpreted particularly cautiously given the limitation of the present meta
analysis and the potential publication bias. Authors are urged to follow more
closely the recommendations for reporting epidemiological studies in order to
enhance the capacity for synthesising the evidence.
PMID- 24356062
TI - Meta-analyses to investigate gene-environment interactions in neuroepidemiology.
AB - BACKGROUND: Most chronic neurological diseases are caused by a combination of
multiple genetic and environmental factors. Increasingly, gene-environment
interactions (GxE) are being examined, providing opportunities to combine studies
systematically using meta-analysis. METHODS: Systematic review of the literature
on how to examine GxE using observational study designs, and how to conduct a
meta-analysis of studies on GxE. RESULTS: Most methods and challenges related to
a standard meta-analysis apply to a GxE meta-analysis. There are, however, some
substantive differences. With GxE, there is the capability of using a case-only
design. Research on GxE interactions may be more prone to publication bias, since
interactions are usually not the primary hypothesis and only 'exciting'
significant GxE findings are reported out of a range of secondary analyses. In
disease aetiology research, there has been debate whether to measure interaction
on a multiplicative or additive scale. There are some significant challenges
associated with measuring interaction on an additive scale, and thus the uptake
of the measures of additive interaction has been limited. As a result, the
methods of analysing interaction have been less consistent and reporting has been
highly variable. We suggest using the STROBE/STREGA reporting guidelines to allow
evaluation of interaction on both scales. CONCLUSIONS: We identified a number of
differences of a GxE meta-analysis over a standard meta-analysis. Awareness of
these issues is important. Using established reporting guidelines for GxE studies
is recommended. The development of consortia for neurological disorders that
include both genetic and environmental data might offer benefits for GxE meta
analyses in the future.
PMID- 24356063
TI - Overview of systematic reviews and meta-analyses of acupuncture for stroke.
AB - BACKGROUND: We aimed to systematically overview published systematic reviews and
meta-analyses in order to identify whether and when acupuncture is an effective
treatment for stroke and stroke-related disorders. We also hoped to identify the
best directions for future research in this area. METHODS: Systematic reviews and
meta-analyses of randomized controlled trials (RCTs) and quasi-RCTs evaluating
the efficacy of acupuncture to treat stroke or stroke-related conditions were
included. Electronic searches were conducted in the Cochrane Database of
Systematic Reviews, Ovid MEDLINE, CINAHL, Ovid EMBASE, EBSCO Allied and
Complementary Medicine (AMED) database, Chinese Biological Medicine Database, and
Chinese National Knowledge Infrastructure Database. Two authors independently
assessed the compliance of studies with eligibility criteria, and extracted data
from included studies. The quality of systematic reviews was assessed according
to the Overview Quality Assessment Questionnaire. RESULTS: A total of 24
systematic reviews were included, of which 4 (16.7%) were Cochrane systematic
reviews and 20 (83.3%) were non-Cochrane reviews. Acupuncture was analyzed as an
acute stroke intervention in 3 reviews (12.5%), as an approach to stroke
rehabilitation in 6 (25%), and as an intervention to treat various stroke-related
disorders in the remaining 15 (62.5%). Reviews analyzing death or
dependency/disability as the primary outcome reported no statistically
significant difference between acupuncture and nonacupuncture control treatments.
In contrast, reviews in which the outcome was improvement in global neurological
deficit scores or performance on the video-fluoroscopic swallowing study test or
water-swallowing test often reported that acupuncture was superior to control
treatment. The quality of 10 reviews was 'poor', 6 reviews were 'moderate' and 8
were 'good'. CONCLUSIONS: The available evidence suggests that acupuncture may be
effective for treating poststroke neurological impairment and dysfunction such as
dysphagia, although these reported benefits should be verified in large, well
controlled studies. On the other hand, the available evidence does not clearly
indicate that acupuncture can help prevent poststroke death or disability, or
ameliorate other aspects of stroke recovery, such as poststroke motor
dysfunction. These findings suggest that researchers should focus on the
potential application of acupuncture to treat poststroke neurological impairment
and dysfunction and on the development of more precise tools to assess these
improvements after stroke.
PMID- 24356064
TI - Advances in meta-analysis: examples from internal medicine to neurology.
AB - OBJECTIVE: We review the state of the art in meta-analysis and data pooling
following the evolution of the statistical models employed. METHODS: Starting
from a classic definition of meta-analysis of published data, a set of apparent
antinomies which characterized the development of the meta-analytic tools are
reconciled in dichotomies where the second term represents a possible
generalization of the first one. Particular attention is given to the generalized
linear mixed models as an overall framework for meta-analysis. Bayesian meta
analysis is discussed as a further possibility of generalization for sensitivity
analysis and the use of priors as a data augmentation approach. RESULTS: We
provide relevant examples to underline how the need for adequate methods to solve
practical issues in specific areas of research have guided the development of
advanced methods in meta-analysis. CONCLUSIONS: We show how all the advances in
meta-analysis naturally merge into the unified framework of generalized linear
mixed models and reconcile apparently conflicting approaches. All these complex
models can be easily implemented with the standard commercial software available.
PMID- 24356065
TI - Epigenetics: a lingering smell?
PMID- 24356071
TI - Sensory neurons and circuits mediating itch.
AB - Chemicals that are used experimentally to evoke itch elicit activity in diverse
subpopulations of cutaneous pruriceptive neurons, all of which also respond to
painful stimuli. However, itch is distinct from pain: it evokes different
behaviours, such as scratching, and originates from the skin or certain mucosae
but not from muscle, joints or viscera. New insights regarding the neurons that
mediate the sensation of itch have been gained from experiments in which gene
expression has been manipulated in different types of pruriceptive neurons as
well as from comparisons between psychophysical measurements of itch and the
neuronal discharges and other properties of peripheral and central pruriceptive
neurons.
PMID- 24356072
TI - Transcranial Doppler ultrasonography CO2 reactivity does not predict recurrent
ischaemic stroke in patients with symptomatic carotid artery occlusion.
AB - BACKGROUND: Patients with transient ischaemic attacks (TIAs) or minor disabling
ischaemic stroke associated with an internal carotid artery (ICA) occlusion have
a high risk of recurrent stroke in case of compromised cerebral blood flow.
Recent studies showed that increased oxygen extraction fraction measured by
positron emission tomography (PET) is still an independent predictor of
subsequent stroke under current medical treatment, but PET facilities are not
widely available. Transcranial Doppler (TCD) ultrasonography CO2 reactivity is a
cheap and non-invasive alternative to measure haemodynamic compromise. The aim of
our study was to investigate whether TCD CO2 reactivity is an independent
predictor of recurrent ischaemic stroke in a large cohort of patients with
symptomatic ICA occlusion in a time where rigorous control of vascular risk
factors has been widely implemented in clinical practice. METHODS: Between July
1995 and December 2009, we included consecutive patients with TIAs or minor
disabling ischaemic stroke (modified Rankin Scale <=3) associated with ICA
occlusion who were referred to the University Medical Centre Utrecht, The
Netherlands. All patients were treated with antiplatelet therapy and received
rigorous control of vascular risk factors, including statins, treatment for
diabetes and hypertension and lifestyle advices. CO2 reactivity was measured with
TCD within 3 months after presentation. We determined the predictive value of TCD
CO2 reactivity for recurrent ischaemic stroke using Cox proportional hazard
analysis. RESULTS: We included 201 patients with a median follow-up time of 7.1
years. Mean CO2 reactivity was 15% (+/-20 standard deviation). The annual rate
for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2]
and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant
relationship between CO2 reactivity and the risk of ipsilateral [hazard ratio
(HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any
recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis
showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0)
for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI
1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent
stroke. CONCLUSIONS: In patients with TIAs or non-disabling stroke associated
with occlusion of the carotid artery, the long-term annual risk of stroke is
generally low with careful control of vascular risk factors. Impaired CO2
reactivity measured within 3 months after presentation does not identify the
subgroup of patients at high risk of recurrent ischaemic stroke.
PMID- 24356073
TI - Evaluation of a specialist nurse-led hypertension clinic with consultant backup
in two inner city general practices: randomized controlled trial.
AB - BACKGROUND: Although practice nurses are increasingly involved in hypertension
management, there is little robust evidence of effectiveness. OBJECTIVE: To
evaluate the effect of a specialist nurse-led hypertension clinic with consultant
backup on change in systolic blood pressure. DESIGN: Randomized trial. SETTING:
Two inner city general practices. Participants. Three hundred and fifty-three
patients, mean age 62 years (range 18-99), with last recorded blood pressure >=
British Hypertension Society audit standard were randomly allocated to the nurse
led clinic or usual care. Intervention. Patients received a letter informing them
that their last blood pressure was over target and inviting them to the clinic.
After assessment at the clinic, the nurse discussed any changes in anti
hypertensive treatment with a visiting consultant and the patient's GP, and
followed up the patient over 6 months until blood pressure targets were achieved.
MAIN OUTCOME MEASURE: Reduction in systolic blood pressure, assessed using two
audits of the practices' computerized records where blood pressure was measured
independently by practice staff before and after the intervention period.
RESULTS: Follow-up was 89% (313/353). There was greater reduction in systolic
blood pressure in the clinic group (n = 144) than usual care group (n = 169,
adjusted difference 4.4 mmHg; 95% CI 0.7 to 8.2). Of 167 patients randomly
selected for the clinic, 91 (55%) attended, 49 had blood pressure above target
when measured according to protocol and 26 had their anti-hypertensive treatment
intensified by their GP. CONCLUSION: Invitation to a specialist nurse-led
hypertension clinic with consultant back up was associated with reduced systolic
blood pressure.
PMID- 24356070
TI - Branch management: mechanisms of axon branching in the developing vertebrate CNS.
AB - The remarkable ability of a single axon to extend multiple branches and form
terminal arbors enables vertebrate neurons to integrate information from
divergent regions of the nervous system. Axons select appropriate pathways during
development, but it is the branches that extend interstitially from the axon
shaft and arborize at specific targets that are responsible for virtually all of
the synaptic connectivity in the vertebrate CNS. How do axons form branches at
specific target regions? Recent studies have identified molecular cues that
activate intracellular signalling pathways in axons and mediate dynamic
reorganization of the cytoskeleton to promote the formation of axon branches.
PMID- 24356074
TI - Bimonthly ranibizumab for neovascular age-related macular degeneration.
AB - BACKGROUND/PURPOSE: Recently, aflibercept was proposed with a protocol of a
bimonthly fixed regimen. Our purpose was to evaluate the results of this regimen
in patients treated with ranibizumab. METHOD: We conducted a retrospective
analysis of consecutive patients with naive neovascular age-related macular
degeneration treated with a bimonthly fixed regimen of intravitreal injections of
ranibizumab after 3 monthly injections. Examination was performed every 4 weeks
for 52 weeks, with the possibility of unscheduled rescue injections of
ranibizumab. RESULTS: A total of 27 patients, 24 women and 3 men, aged from 68 to
90 years (mean: 81.2) were analyzed; 25 eyes (92.5%) lost <15 letters. Mean BCVA
rose from 58.3 (range +/- 12.9) to 66.7 (range +/- 14.3) letters. The mean visual
gain was 8.40 (range +/- 13.2) letters; 11 patients (40.7%) gained >= 15 letters.
The mean number of injections of ranibizumab was 8.77. CONCLUSION: Bimonthly
intravitreal ranibizumab achieved satisfactory visual results. However, patients
who required additional injections did not experience significant visual gain.
PMID- 24356075
TI - Correlations between lithium local structure and electrochemistry of layered
LiCo(1-2x)Ni(x)Mn(x)O2 oxides: 7Li MAS NMR and EPR studies.
AB - Advanced (7)Li MAS NMR technologies and high frequency EPR are combined to
identify structural motifs and their relation to electrochemical properties of
layered lithium-cobalt-nickel-manganese oxides LiCo1-2xNixMnxO2 (0 < x <= 0.5)
used as cathode materials in lithium ion batteries. Structural-chemical shift
regularities were established by systematic variation of the ratio of diamagnetic
Co(3+) to paramagnetic Ni/Mn ions with variable valences. While EPR allows
identifying the oxidation state of transition metal ions inside the layers, (7)Li
NMR probes the local structure of Li with respect to transition metal ions
located in two adjacent layers. For assignment of the lithium chemical shifts, we
examine first magnetically diluted LiCo1-2xNixMnxO2 with x = 0.02, where
paramagnetic ions are stabilized only in Mn(4+) and Ni(3+) form. Then the studies
are extended towards the intermediate compositions with x = 0.10 and 0.33,
containing simultaneously paramagnetic Mn(4+), Ni(3+) and Ni(2+) ions and
diamagnetic Co(3+) ions. The benefit of using NMR with ultrafast spinning rates
is demonstrated for the end composition LiNi0.5Mn0.5O2 having only paramagnetic
Ni(2+) and Mn(2+) ions. The local structure of Li is quantified in respect of the
number of Ni(2+) and Mn(4+) neighbors. It has been demonstrated that Ni(2+) and
Mn(4+) are non-randomly distributed around Li and their distribution depends on
the method of synthesis. The extent of local cationic order and its effect on the
electrochemical properties of LiNi0.5Mn0.5O2 are discussed.
PMID- 24356076
TI - MicroRNAs contribute to promyelocyte apoptosis in As2O3-treated APL cells.
AB - BACKGROUND: Arsenic trioxide (As2O3), an ancient drug used in traditional Chinese
medicine, has substantial anticancer activities, especially in the treatment of
patients suffering from acute promyelocytic leukemia (APL); however the
underlying mechanisms are not well understood. METHODS: MTT assay was used to
detect the cell viability. Flow Cytometry analysis and caspase-3 activity assay
were used to measure apoptosis of APL cells. Caspase-3 and Bax levels were
analyzed by western blot and let-7d and miR-766 levels were determined by real
time RT-PCR. RESULTS: As2O3 significantly inhibited cell viability and induced
apoptosis in APL cells. Several microRNAs, including let-7d and miR-766, were
dysregulated in APL cells treated with As2O3. The expression of caspase-3 and
Bax, which are targets of let-7d and miR-766, respectively, were up-regulated in
As2O3 treated cells. Transfection of let-7d and miR-766 into NB4 cells decreased
the expression of caspase-3 and Bax, respectively. Correspondingly, transfection
of these microRNAs increased NB4 cell viability. As2O3 induced degradation of
promyelocytic leukemia (PML), and then induced the down-regulation of both let-7d
and miR-766 in NB4 cells. CONCLUSIONS: We construct a dysregulated microRNA
network involved in As2O3-induced apoptosis in APL. Targeting this network may be
a new strategy for the prevention of side effects associated with APL treatment
with As2O3.
PMID- 24356077
TI - An exchange of ideas on the World Report on Disability.
PMID- 24356078
TI - Analysis and implementation of a World Health Organization health report:
methodological concepts and strategies.
AB - A long-standing scientific discourse on the use of health research evidence to
inform policy has come to produce multiple implementation theories, frameworks,
models, and strategies. It is from this extensive body of research that the
authors extract and present essential components of an implementation process in
the health domain, gaining valuable guidance on how to successfully meet the
challenges of implementation. Furthermore, this article describes how
implementation content can be analyzed and reorganized, with a special focus on
implementation at different policy, systems and services, and individual levels
using existing frameworks and tools. In doing so, the authors aim to contribute
to the establishment and testing of an implementation framework for reports such
as the World Health Organization World Report on Disability, the World Health
Organization International Perspectives on Spinal Cord Injury, and other health
policy reports or technical health guidelines.
PMID- 24356079
TI - The United States' response to the World Report on Disability.
AB - The 2011 Annual Disability Status Report notes a disability prevalence rate of
12.1% in the United States. People with disabilities of all ages are increasing
in prevalence, and the prevalence increases with age. People with disabilities
are high users of health care, have less social participation, and have a higher
risk for poverty. Although the United States has a robust history of policy and
legislation related to disability and rehabilitation, the ratification of the
United Nations Conventions on the Rights of People with Disabilities recently
failed in the United States Congress. However, in general, the United States is
positioned fairly well regarding most aspects of rehabilitation including a
strong rehabilitation science providing a sound base for evidence-based practice.
Three key areas of further development emerge: education about disability and
benefits of rehabilitation to decision makers and administrators who are
concerned with the implementation of the Affordable Care Act, advocacy for a more
robust organized presence and acknowledgement of rehabilitation science and
research, and advocacy for education about disability and rehabilitation for
physicians-in-training.
PMID- 24356080
TI - Disability and rehabilitation in Mexico.
AB - Recent disability-related data are available from the 13th National Census of
Population and Housing, which was performed in 2010. Disability assessment
followed the recommendations of the Washington Group on Disability Statistics and
identified 5,739,270 (5.1%) persons with disability, 51.1% of whom were women.
Almost 60% of all persons 85 yrs or older reported disabilities. Policies and
legislation endorse the rights of persons with disabilities. However, little is
known about the real-life situation of persons with disabilities in Mexico as
well as the met and unmet needs for rehabilitation. Rehabilitation services in
Mexico are mainly organized by the Mexican Institute of Social Security. Because
of the increasing need for rehabilitation, an innovative model of small first
level rehabilitation services has been designed and successfully implemented.
This model has increased the capacity of rehabilitation services by 60% since
2003.
PMID- 24356081
TI - The World Report on Disability: a challenge for rehabilitation medicine.
AB - To analyze the life situation of people with disabilities and to summarize the
evidence of measures to support their participation, the World Health Assembly
requested the World Health Organization to produce a World Report on Disability.
This article highlights some of the main contents of the World Report on
Disability, with a special focus on the rehabilitation chapter. It starts by
presenting epidemiologic findings on the global disability prevalence, views on
the role of rehabilitation medicine, discrepancies between met and unmet needs,
and challenges for the quality of rehabilitation services and ends with an
outlook on the report's recommendations and efforts toward their implementation.
PMID- 24356082
TI - Reflecting the World Report on Disability: a report from Sweden.
AB - There is a range of statistics in Sweden regarding people with functional
limitations available from different authorities presenting diverging
information. Although healthcare and social welfare legislations aim for equal
access and treatment, surveys about unmet needs show that opportunities for
rehabilitation are unequal among diagnoses and around the country and
insufficient in the long-term. There is also a law granting certain supports and
services to those people who are considered to be in need of having someone to
speak for them. Disability-related services are tax financed with a symbolic fee.
Rehabilitation is performed by not only physical and rehabilitation medicine
specialists. Rehabilitation research is mainly within healthcare science but also
in social science. Disability services need better coordination, and an agency
has recently been founded with this responsibility. More politicians should
engage in disability-related issues, and more people with disability should get
into politics.
PMID- 24356083
TI - Implementing the World Report on Disability in West Africa: challenges and
opportunities for Ghana.
AB - Disability issues have taken a prominent role on international stages in recent
years. Beginning with the May 2005 World Health Assembly Resolution 58.23 and
culminating in the June 2011 World Bank and World Health Organization World
Report on Disability, comprehensive disability analyses from nations at various
stages of development can now be accessed and used by relevant stakeholders in
health, policy, and aide arenas. The implementation of this landmark report is
critical for the advancement of social inclusion in diverse countries, including
those with limited resources. However, activating the World Report on Disability
in resource-limited countries remains a significant challenge because of
threadbare data and cultural, institutional, and physical barriers to social
inclusion. This review summarizes current national disability data and describes
challenges and opportunities for the implementation of the World Report on
Disability in Ghana. As a structural point of departure, the article uses the
three broad categories of challenges outlined by the World Health Organization:
attitudinal, physical, and institutional.
PMID- 24356084
TI - The World Report on Disability and recent developments in South Korea.
AB - The latest National Survey on Persons with Disabilities estimated 2,683,400
persons with disabilities in South Korea, of whom 58% were men and 42% were
women. People with physical disability represent approximately 50% of the entire
population with disability. Disability-related policies and services to improve
the participation of persons with disabilities have been expanded in the last
decades, guided by 5-yr plans. The number of physiatrists has increased, although
it still varies significantly by location. As part of the comprehensive measures
to expand rehabilitation services, several regional rehabilitation centers have
been established. In addition, a community-based rehabilitation program has been
implemented that comprises Strong Point Public Health Centers, which provide
local health promotion programs for persons with disabilities, family support
programs, and community participation programs. As the aged population increases,
it is predicted that the population of persons with disabilities in South Korea
will also increase. A long-term and innovative financial model will be required
to meet the corresponding needs. A recent milestone of evidence-based practice is
the publication of Clinical Practice Guideline for Stroke Rehabilitation in
Korea.
PMID- 24356085
TI - The problems of people with disability in Indonesia and what is being learned
from the World Report on Disability.
AB - Recent epidemiologic findings indicate that 1.8% of the Indonesian population
"have extreme problems" and 19.5% "have problems" in various aspects of their
ability to carry out daily activities. People with disability (PWD) have a high
risk for poverty in Indonesia, and there are strong prejudices that presume
unproductivity and dependency. Disability policies are integrated through a
National Plan of Action. However, the existing number of human resources in the
field of medical rehabilitation is still too low compared with the existing
needs. This is true also for the budget for rehabilitation services. Several
issues are identified that need action to improve the inclusion of PWD and to
ensure their dignity including supporting a perception of PWD as active and equal
citizens, assessing accurate data about the disability prevalence, strengthening
organizations of PWD, building educational capacities for PWD, developing
preventive strategies, and international cooperation.
PMID- 24356086
TI - Dissemination, analysis, and implementation of the World Report on Disability:
the roadmap of the International Society for Physical and Rehabilitation
Medicine.
AB - The International Society for Physical and Rehabilitation Medicine has recognized
the World Report on Disability as a guide for its future activities and endorsed
its responsibility to disseminate, to analyze, and to implement the report's
recommendations. The activities of the International Society for Physical and
Rehabilitation Medicine on the global stage are embedded in a strategy that
includes national and regional associations. This article reports on recent and
forthcoming activities of the International Society for Physical and
Rehabilitation Medicine regarding the World Report on Disability and identifies
five major challenges that will impact future International Society for Physical
and Rehabilitation Medicine activities. These challenges relate to (1) education
and training, (2) the support of strong role models, (3) disaster management, (4)
the development of innovative rehabilitation services, and (5) rehabilitation
research.
PMID- 24356088
TI - Anisotropy of electromigration-induced void and island drift.
AB - By means of our novel self-learning kinetic Monte Carlo model (Latz et al 2012 J.
Phys.: Condens. Matter 24 485005) we study the electromigration-induced drift of
monolayer voids and islands on unpassivated surfaces of single crystalline
Ag(111) and Ag(001) films at the atomic scale. Regarding the drift velocity, we
find a non-monotonic size dependence for small voids. The drift direction is
aligned with the electromigration force only along high symmetry directions,
while halfway between, the angle enclosed by them is maximal. The magnitude of
these directional deviations strongly depends on the system parameter, which are
investigated in detail. The simulation results are in accordance with void motion
observed in experiments performed on Ag(111).
PMID- 24356087
TI - Twitter and public health.
AB - Twitter can serve as a powerful communication modality to both "push" and "pull"
public health data; each user is a potential public health sensor and actor.
However, in 2012, only 8% of local health departments had Twitter accounts. We
outline how Twitter works, describe how to access public tweets for public health
surveillance purposes, review the literature on Twitter's current and potential
role supporting public health's essential services, summarize Twitter's
limitations, and make recommendations for health department use.
PMID- 24356089
TI - Toll-like receptor 4 is required for the cytotoxicity of cytokine-induced killer
cells.
AB - Cytokine-induced killer (CIK) cells are heterogeneous effector T cells with
diverse T-cell receptor specificities with non-major histocompatibility complex
restricted cytolytic activities against tumor cells and are considered a
promising therapeutic approach against hematologic malignancy. Recently, it has
been reported that IL-15-activated CIK cells are superior to cells generated
according to the standard protocol; however, the underlying mechanism remains to
be elucidated. In the present study, we found that in IL-15-stimulated CIK cells,
Toll-like receptor 4 (TLR4) expression was upregulated. Upon knockdown of TLR4,
the cytolytic activity was considerably compromised. Re-expression of TLR4 in CIK
cells restored their function, confirming the essential role of TLR4 in CIK cell
cytotoxicity. Collectively, our study demonstrated that TLR4 was essential for
the cytotoxicity of CIK cells against tumor cells, which might provide a novel
approach to promote the therapeutic efficacy of CIK cells against hematologic
malignancy.
PMID- 24356090
TI - Clinical significance of downstaging in patients with limited-disease small-cell
lung cancer.
AB - BACKGROUND: We investigated the effect of downstaging on OS in LD-SCLC patients
treated with first-line treatment. PATIENTS AND METHODS: We retrospectively
reviewed 210 LD-SCLC patients who were treated with first-line treatment at Seoul
National University Hospital between April 1999 and November 2012. Compared with
initial tumor, node, metastases (TNM) stage, cases that showed a lower TNM stage
after treatment were defined as 'downstaging.' The relationship between
downstaging and OS was analyzed, and a subgroup analysis on the responders was
performed. RESULTS: After first-line treatment, 78 (37.1%) patients achieved
complete response, 97 (46.2%) achieved PR, and 35 (16.7%) experienced stable
disease or progressive disease. A hundred and fifty one patients (71.9%) showed
downstaging of their diseases, and the remaining 59 patients (28.1%) showed no
change or upstaging. The median OS for patients achieving downstaging and no
change/upstaging were 32.8 months and 13.1 months, respectively (P < .001). Of
the 97 patients who achieved PR, the OS was significantly longer in patients who
showed downstaging than those who did not (25.8 months vs. 13.8 months,
respectively; P = .004). In multivariate analyses, female sex, downstaging, lower
initial TNM stage, and prophylactic cranial irradiation were independent good
prognostic factors for OS. CONCLUSION: Downstaging might be an independent good
prognostic factor in LD-SCLC. Specifically, downstaging is expected to be useful
for stratification of patients achieving PR. Further prospective studies are
warranted to verify whether patients who achieved PR without downstaging can be
candidates for consolidation treatments after first-line treatment.
PMID- 24356091
TI - Whole ceramic-like microreactors from inorganic polymers for high temperature
or/and high pressure chemical syntheses.
AB - Two types of whole ceramic-like microreactors were fabricated from inorganic
polymers, polysilsesquioxane (POSS) and polyvinylsilazane (PVSZ), that were
embedded with either perfluoroalkoxy (PFA) tube or polystyrene (PS) film
templates, and subsequently the templates were removed by physical removal (PFA
tube) or thermal decomposition (PS). A POSS derived ceramic-like microreactor
with a 10 cm long serpentine channel was obtained by an additional "selective
blocking of microchannel" step and subsequent annealing at 300 degrees C for 1
h, while a PVSZ derived ceramic-like microreactor with a 14 cm long channel was
yielded by a co-firing process of the PVSZ-PS composite at 500 degrees C for 2 h
that led to complete decomposition of the film template leaving a microchannel
behind. The obtained whole ceramic-like microfluidic devices revealed excellent
chemical and thermal stabilities in various solvents, and they were able to
demonstrate unique chemical performance at high temperature or/and high pressure
conditions such as Michaelis-Arbuzov rearrangement at 150-170 degrees C, Wolff
Kishner reduction at 200 degrees C, synthesis of super-paramagnetic Fe3O4
nanoparticles at 320 degrees C and isomerisation of allyloxybenzene to 2
allylphenol (250 degrees C and 400 psi). These economic ceramic-like
microreactors fabricated by a facile non-lithographic method displayed excellent
utility under challenging conditions that is superior to any plastic
microreactors and comparable to glass and metal microreactors with high cost.
PMID- 24356092
TI - Occupational radiation exposure among the staff of departments of nuclear
medicine and diagnostic radiology in Kuwait.
AB - OBJECTIVES: To investigate radiation exposure among the staff of departments of
nuclear medicine (NM) and diagnostic radiology (DR) during 2008 and 2009 and to
compare the mean doses received with the limit of 20 mSv/year of the
International Commission of Radiological Protection (ICRP). MATERIALS AND
METHODS: The whole-body dose or effective dose, i.e. Hp(10), and the skin dose,
i.e. Hp(0.07), of the staff of departments of NM and DR in Kuwait for the period
of 2008 and 2009 were taken from the national thermoluminescent dosimetry
database. A total of 1,780 radiation workers, grouped as NM physicians,
radiologists, NM technologists, and DR technologists, from 7 departments of NM
and 12 departments of DR were included. The annual average Hp(10) and Hp(0.07)
were calculated for each group and comparisons were made between the groups and
the years. A two-sided Mann-Whitney test was carried out, at the p = 0.05 level,
to compare the means. The mean Hp(10) was compared with the limits of the ICRP.
RESULTS: Of the 16 distributions of Hp(10) and Hp(0.07), 10 were normal, with a
mean annual Hp (10) in 2008 of 1.06, 1.03, 1.07, and 1.05 mSv for NM physicians,
radiologists, NM technologists, and DR technologists, respectively. The
corresponding Hp(0.07) values for 2008 were 1.03, 1.00, 1.05, and 1.03 mSv,
respectively. Small but significant (p < 0.001) reductions in Hp(10) and Hp(0.07)
were observed in 2009 for NM technologists and DR technologists. In all other
cases, no significant (p > 0.072) differences were found. CONCLUSION: The annual
average Hp(10) was well below the limit of the ICRP.
PMID- 24356093
TI - External validation of nomogram predicting the probability of specimen-confined
disease (pT2-3a, R0N0) in patients undergoing radical prostatectomy and pelvic
lymph node dissection.
AB - INTRODUCTION: Before radical prostatectomy (RP), a nomogram [Briganti et al., Eur
Urol 2012;61:584-592] permits to measure the probability of specimen-confined
(SC) disease (pT2-pT3a, node negative with negative margins) in high-risk
prostate cancer (PCa). The aim of our study was to perform an external validation
of this nomogram. MATERIALS AND METHODS: Between 2007 and 2011, 623 patients with
high-risk PCa (prostate-specific antigen (PSA) >20 ng/ml and/or biopsy Gleason
score >=8 and/or clinical stage T3) underwent RP and pelvic lymph node dissection
at tertiary referral centers. Multivariable logistic regression models predicting
the presence of SC disease were built in; we then used the area under curve of
the receiver operating characteristic analysis to quantify accuracy of the
nomogram to predict SC disease. The extent of over- or underestimation was
evaluated within calibration plots. RESULTS: 29% (181/623) of men had SC disease
at RP. Preoperative PSA, biopsy Gleason score and stage differed significantly
(all p < 0.001) between men with SC disease and those without. External
validation of the nomogram showed an acceptable accuracy (area under curve: 66.3,
95% CI 62.4-70%) and a perfect calibration plot. CONCLUSIONS: The external cohort
validates the original nomogram, with perfect calibration characteristics. The
adequate although reduced accuracy may reflect the wide spectrum and behavior of
the so-called high-risk PCa.
PMID- 24356094
TI - Molecular classification of metaplastic carcinoma using surrogate
immunohistochemical staining.
AB - OBJECTIVE: The purpose of this study is to investigate molecular subtyping and
its implications on metaplastic carcinoma according to surrogate
immunohistochemical (IHC) staining. METHODS: Following tissue microarray analysis
of 34 cases of metaplastic carcinoma, IHC staining for cytokeratin (CK) 5/6,
epidermal growth factor receptor (EGFR), claudin-3, claudin-4, claudin-7, E
cadherin, STAT-1, androgen receptor and GGT was performed and classified into
basal-like, molecular apocrine, claudin-low, immune-related, mixed and null
types. RESULTS: Among the 34 cases of metaplastic carcinoma, 13 were of the basal
like type (35.2%), 9 of the mixed type (26.5%), 8 of the null type (23.5%), 3 of
the claudin-low type (8.8%), and 1 was of the molecular apocrine type (2.9%).
Depending on the cell type, there were differences between molecular subtypes,
with the matrix-producing type occupying the largest proportion in the basal
like, null and mixed types. The spindle cell type represented the largest
proportion in the claudin-low and molecular apocrine types, and the squamous cell
type characterized the largest proportion in the basal-like type. CONCLUSION:
Following molecular subtyping of metaplastic carcinomas using surrogate IHC
markers, the largest number of cases was of the basal-like type, followed by the
mixed, null, claudin-low and molecular apocrine types. There were differences
between molecular subtypes according to the cell type.
PMID- 24356095
TI - Effects of uric acid levels on outcome in severe ischemic stroke patients treated
with intravenous recombinant tissue plasminogen activator.
AB - Uric acid (UA) has been known to be a neuroprotective antioxidant because of its
free radical scavenger activity. We studied the influence of UA in patients with
acute ischemic stroke after thrombolytic therapy. Two hundred eighteen
consecutive patients treated with intravenous thrombolysis were included in this
analysis. We analyzed the relationship between serum UA levels obtained at the
emergency department and clinical outcomes. Early improvement and excellent
functional outcomes were measured using the National Institutes of Health Stroke
Scale (NIHSS) 24 h after onset and the modified Rankin scale after 3 months.
There was no significant relationship between serum UA levels and early
improvement or excellent functional outcome in the total patients (p = 0.583 and
p = 0.082, respectively). However, in patients with severe baseline stroke
deficits (NIHSS score >=15), higher-tertile UA levels were significantly
associated with excellent functional outcomes (p = 0.003). Excellent functional
outcomes in patients with severe baseline disability might have a significant
association with serum UA levels particularly in men but not in women (p = 0.007
in men and p = 0.621 in women). Increased serum UA levels might be associated
with better outcomes in ischemic stroke patients treated with intravenous
thrombolysis, but the effectiveness of UA can differ by initial stroke severity
and gender.
PMID- 24356096
TI - Molecular profiling of the residual disease of triple-negative breast cancers
after neoadjuvant chemotherapy identifies actionable therapeutic targets.
AB - Neoadjuvant chemotherapy (NAC) induces a pathologic complete response (pCR) in
approximately 30% of patients with triple-negative breast cancers (TNBC). In
patients lacking a pCR, NAC selects a subpopulation of chemotherapy-resistant
tumor cells. To understand the molecular underpinnings driving treatment
resistant TNBCs, we performed comprehensive molecular analyses on the residual
disease of 74 clinically defined TNBCs after NAC, including next-generation
sequencing (NGS) on 20 matched pretreatment biopsies. Combined NGS and digital
RNA expression analysis identified diverse molecular lesions and pathway
activation in drug-resistant tumor cells. Ninety percent of the tumors contained
a genetic alteration potentially treatable with a currently available targeted
therapy. Thus, profiling residual TNBCs after NAC identifies targetable molecular
lesions in the chemotherapy-resistant component of the tumor, which may mirror
micrometastases destined to recur clinically. These data can guide biomarker
driven adjuvant studies targeting these micrometastases to improve the outcome of
patients with TNBC who do not respond completely to NAC. SIGNIFICANCE: This study
demonstrates the spectrum of genomic alterations present in residual TNBC after
NAC. Because TNBCs that do not achieve a CR after NAC are likely to recur as
metastatic disease at variable times after surgery, these alterations may guide
the selection of targeted therapies immediately after mastectomy before these
metastases become evident.
PMID- 24356098
TI - Antiangiogenic therapies: going beyond their limits.
AB - Tumor growth requires induction of an angiogenic program, and targeting of this
program with antiangiogenic drugs shows an impact on tumor progression. However,
although they are effective at reducing angiogenesis, these therapies have not
produced widespread or enduring clinical benefit, which openly exposes their
limitations. Here, we describe the current limitations of these therapies,
including the known mechanisms and current controversies. Further, we present
some of the recent approaches to predict these limitations and strategies to
overcome them. With the development of meaningful predictive biomarkers and
effective treatments that impede these limitations, longer and more robust
efficacies will be achieved for a wider population of patients.
PMID- 24356097
TI - Evolution of DNA methylation is linked to genetic aberrations in chronic
lymphocytic leukemia.
AB - Although clonal selection by genetic driver aberrations in cancer is well
documented, the ability of epigenetic alterations to promote tumor evolution is
undefined. We used 450k arrays and next-generation sequencing to evaluate
intratumor heterogeneity and evolution of DNA methylation and genetic aberrations
in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient
differences in intratumor methylation heterogeneity, with genetically clonal
cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a
monoallelically methylated state. Increasing methylation heterogeneity correlates
with advanced genetic subclonal complexity. Selection of novel DNA methylation
patterns is observed only in cases that undergo genetic evolution, and
independent genetic evolution is uncommon and is restricted to low-risk
alterations. These results reveal that although evolution of DNA methylation
occurs in high-risk, clinically progressive cases, positive selection of novel
methylation patterns entails coevolution of genetic alteration(s) in CLL.
PMID- 24356099
TI - Dexamethasone intravitreal implant for treatment of patients with persistent
diabetic macular edema.
AB - PURPOSE: To report the 6-month anatomical and best-corrected visual acuity (BCVA)
response after primary intravitreal dexamethasone implantation (Ozurdex(r)) in
patients with refractory diabetic macular edema (DME). METHODS: Retrospective
review of the medical records of 58 patients with decreased visual acuity, due to
refractory DME, who underwent a single injection of Ozurdex between November 2010
and January 2012, at the Instituto de Microcirurgia Ocular, Barcelona, Spain.
RESULTS: At baseline, the mean foveal thickness (FT) was 543.24 +/- 156.51 MUm.
Mean (+/-SD) values of FT did decrease to 346.82 +/- 123.74 MUm at month 1 and
341.12 +/- 129.64 MUm at month 3. Data on the 6-month follow-up showed a mild
increase to 420.16 +/- 152.15 MUm. All of the FT reduction outcomes were
statistically significant, with respect to baseline data (p = 0.0001). The
baseline BCVA data was 0.66 +/- 0.36 logarithm of the minimum angle of resolution
(logMAR). The mean BCVA improved to 0.52 +/- 0.32 logMAR (p = 0.0001) and 0.44 +/
0.27 logMAR (p = 0.0001) after 1 and 3 months, respectively. At the last visit
(6-month follow-up), the mean BCVA increased to 0.51 +/- 0.31 logMAR (p =
0.0001). CONCLUSIONS: In this study, intravitreal treatment with a dexamethasone
implant safely reduced DME and improved visual acuity in a difficult-to-treat
patient population with long-standing refractory DME.
PMID- 24356101
TI - An estimation of molecular dynamic behaviour in a liquid using core-loss
spectroscopy.
AB - We report an effective approach for estimating the dynamic behaviour of molecules
in liquid from their core-loss spectra by combining molecular dynamics
simulations and first-principles band-structure calculations. The carbon K-edge
of the technologically important methanol was calculated, and the experimental
spectra were well reproduced using the presented calculation method, which
effectively included multiple-molecule interactions. Several peaks arose from the
methanol molecules with different C-O bonding modes, and the splitting of those
peaks was sensitively altered by the magnitude of the dynamic behaviour of
molecules. These findings allow for estimation of the dynamic behaviour of
molecules in liquids using core-loss spectroscopy, and the method offers the
potential to identify the dynamic behaviour of the molecules in liquids with high
spatial resolution, temporal resolution, and sensitivity.
PMID- 24356100
TI - Shunting in acute cerebral venous thrombosis: a systematic review.
AB - BACKGROUND AND PURPOSE: The efficacy of cerebrospinal fluid shunting to reduce
intracranial hypertension and prevent fatal brain herniation in acute cerebral
venous thrombosis (CVT) is unknown. METHOD: From the International Study on
Cerebral Vein and Dural Sinus Thrombosis (ISCVT) and a systematic literature
review, we retrieved acute CVT patients treated only with shunting (external
ventricular drain, ventriculoperitoneal or ventriculojugular shunt). Outcome was
classified at 6 months and final follow-up by the modified Rankin Scale (mRS).
RESULTS: 15 patients were collected (9 from the ISCVT and 6 from the review) who
were treated with a shunt (external ventricular drain in 6 patients, a
ventriculoperitoneal shunt in 8 patients or an unspecified type of shunt in
another one). Eight patients (53.3%) regained independence (mRS 0-2), while 2
patients (13.3%) were left with a severe handicap (mRS 4-6) and 4 (26.7%) died
despite treatment. Five patients with parenchymal lesions were shunted within 48
h from admission deterioration, 4 with an external ventricular drain: 2 (40%)
recovered to independence, 2 (40%) had a severe handicap and 1 (20%) died. In
contrast, all 3 patients with intracranial hypertension and no parenchymal
lesions receiving a ventriculoperitoneal shunt later than 48 h regained
independence. CONCLUSION AND IMPLICATIONS: A quarter of acute CVT patients
treated with a shunt died, and only half regained independence. With the
limitation of the small number of subjects, this review suggests that shunting
does not appear to be effective in preventing death from brain herniation in
acute CVT. We cannot exclude that shunting may benefit patients with sustained
intracranial hypertension and no parenchymal lesions.
PMID- 24356102
TI - Procedure-specific risk factor analysis for the development of severe
postoperative pain.
AB - BACKGROUND: Many studies have analyzed risk factors for the development of severe
postoperative pain with contradictory results. To date, the association of risk
factors with postoperative pain intensity among different surgical procedures has
not been studied and compared. METHODS: The authors selected precisely defined
surgical groups (at least 150 patients each) from prospectively collected
perioperative data from 105 German hospitals (2004-2010). The association of age,
sex, and preoperative chronic pain intensity with worst postoperative pain
intensity was studied with multiple linear and logistic regression analyses.
Pooled data of the selected surgeries were studied with random-effect analysis.
RESULTS: Thirty surgical procedures with a total number of 22,963 patients were
compared. In each surgical procedure, preoperative chronic pain intensity and
younger age were associated with higher postoperative pain intensity. A linear
decline of postoperative pain with age was found. Females reported more severe
pain in 21 of 23 surgeries. Analysis of pooled surgical groups indicated that
postoperative pain decreased by 0.28 points (95% CI, 0.26 to 0.31) on the numeric
rating scale (0 to 10) per decade age increase and postoperative pain increased
by 0.14 points (95% CI, 0.13 to 0.15) for each higher score on the preoperative
chronic pain scale. Females reported 0.29 points (95% CI, 0.22 to 0.37) higher
pain intensity. CONCLUSIONS: Independent of the type and extent of surgery,
preoperative chronic pain and younger age were associated with higher
postoperative pain. Females consistently reported slightly higher pain scores
regardless of the type of surgery. The clinical significance of this small sex
difference has to be analyzed in future studies.
PMID- 24356103
TI - miR-125b promotes cell proliferation by directly targeting Lin28 in glioblastoma
stem cells with low expression levels of miR-125b.
AB - MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein
expression by cleaving or repressing the translation of target mRNAs. Our
previous studies have revealed that miR-125b is a typical overexpressed miRNA in
human primary glioblastoma stem cells (GSCs). Here, we report that miR-125b was
also found to be significantly underexpressed in three primary GSCs.
Characterization of the effects of the underexpressed miR-125b in GSCs showed
that elevated levels of miR-125b inhibited cell growth and induced cell cycle
arrest in the G0/G1 phase in vitro; a reduction in miR-125b levels had the
opposite effect on tumour growth and progression. Further research into the
underlying mechanism demonstrated that miR-125b acts by targeting Lin28 to
regulate cell growth. Lin28 is highly expressed in human embryonic stem cells and
glioblastomas. We showed that the specific repression of Lin28 results in
decreased GSC proliferation, and that the overexpression of Lin28 accelerates
cell proliferation. Our results highlight a novel molecular interaction between
miR-125b and Lin28, and miR-125b may represent a potential novel therapeutic
agent for targeting the proliferation of GSCs. In view of our previous research
showing that miR-125b was overexpressed in GSCs and functioned as an oncogene,
here our finding was not in agreement with our previous report, which implies
that the personalized treatment on GSCs may be necessary and important.
PMID- 24356104
TI - Prognostic value of serum lipoprotein(a) levels in patients with acute ischemic
stroke.
AB - Inflammation plays a crucial role in the pathogenesis and prognosis of stroke.
This study aims to investigate the relationship between acute ischemic stroke
(AIS) and lipoprotein(a) [Lp(a)] levels and to determine the prognosis value of
Lp(a) to predict the functional outcome. A total of 153 patients with AIS and 120
controls were included in the study. Serum Lp(a) levels were examined in both
groups. Severity of the stroke was assessed using the National Institutes of
Health Stroke Scale. The modified Rankin Scale scores at discharge were
determined to establish the prognosis of stroke patients. The prognostic value of
Lp(a) to predict the functional outcome within the time of discharge was analyzed
by logistic regression analysis, after adjusting for the possible confounders.
The results indicated that the serum Lp(a) levels were significantly higher in
AIS patients as compared with normal controls [303 {interquartile range (IQR) 170
529 mg/l} and 144 (IQR 66-252 mg/l), respectively; P=0.000]. In the 52 patients
with an unfavorable functional outcome, serum Lp(a) levels were higher compared
with those in patients with a favorable outcome [213 (IQR 143-347 mg/l) and 559
(IQR 357-845 mg/l), respectively; P=0.000]. In multivariate analysis, there was
an increased risk of unfavorable outcome associated with Lp(a) levels 300 mg/l or
more (odds ratio 3.12; 95% confidence interval 1.55-5.28; P=0.001) after
adjusting for possible confounders. Serum Lp(a) can be considered as an
independent short-term prognostic marker of functional outcome in Chinese
patients with AIS even after correcting for possible confounding factors.
PMID- 24356105
TI - Activation of the medial prefrontal and posterior cingulate cortex during
encoding of negative material predicts symptom worsening in major depression.
AB - Considerable research indicates that depressed individuals have better memory for
negative material than do nondepressed individuals, and that this bias is
associated with differential patterns of neural activation. It is not known,
however, whether these aberrant activation patterns predict illness course. Using
functional neuroimaging, we examined whether change in depressive symptoms is
predicted by baseline patterns of neural activation that underlie negative memory
biases in major depressive disorder. Depressed participants viewed negative and
neutral pictures during functional MRI at baseline and completed an incidental
memory task for these pictures 1 week later. Depression severity was assessed by
administering the Beck Depression Inventory both at baseline (Time 1) and at Time
2, an average of 18 months later. Contrast maps of activation for subsequently
remembered negative versus subsequently remembered neutral pictures were
regressed against change in Beck Depression Inventory scores between Time 1 and
Time 2, controlling for initial symptom severity. Results from this analysis
revealed no associations between memory sensitivity for negative stimuli and
symptom change. In contrast, whole brain analyses revealed significant positive
associations between within-subject changes in depressive symptoms and baseline
neural activation to successfully recalled negative pictures in the posterior
cingulate cortex and medial prefrontal cortex. These findings indicate that
neural activation in cortical midline regions is a better predictor of long-term
symptomatic outcome than is memory sensitivity for negative material.
PMID- 24356106
TI - Early print-tuned ERP response with minimal involvement of linguistic processing
in Japanese Hiragana strings.
AB - The act of reading leads to the development of specific neural responses for
print, the most frequently reported of which is the left occipitotemporal N170
component of event-related potentials. However, it remains unclear whether this
electrophysiological response solely involves print-tuned neural activities. The
present study examined an early print-tuned event-related potential response with
minimal involvement of linguistic processing in a nonalphabetic language.
Japanese Hiragana words, nonwords, and alphanumeric symbol strings were presented
rapidly and the task was to detect the change in color of a fixation cross to
restrict linguistic processing. As a result, Hiragana words and nonwords elicited
a larger posterior N1 than alphanumeric symbol strings bilaterally, irrespective
of intercharacter spacing. The fact that this N1 was enhanced specifically for
rapidly presented Hiragana strings suggests the existence of print-tuned neural
processes that are relatively independent of the influence of linguistic
processing.
PMID- 24356107
TI - Creatine supports propagation and promotes neuronal differentiation of inner ear
progenitor cells.
AB - Long-term propagation of inner ear-derived progenitor/stem cells beyond the third
generation and differentiation into inner ear cell types has been shown to be
feasible, but challenging. We investigated whether the known neuroprotective
guanidine compound creatine (Cr) promotes propagation of inner ear
progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the
formation of spheres over passages. In addition, we studied whether Cr alone or
in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal
differentiation of inner ear progenitors. For this purpose, early postnatal rat
spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as
floating spheres in the absence (controls) or presence of Cr (5 mM) from passage
3 onward. Similarly, dissociated sphere-derived cultures were differentiated for
14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived
cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found
that the cumulative total number of spheres over all passages was significantly
higher after Cr supplementation as compared with controls in all the three inner
ear cultures. In contrast, sphere sizes were not affected by the administration
of Cr. Administration of Cr during differentiation of spiral ganglia cells
resulted in a significantly higher density of beta-III-tubulin-positive cells
compared with controls, whereas densities of myosin VIIa-positive cells in
cultures of utricle and organ of Corti were not affected by the treatment.
Importantly, a combination of Cr with the neurotrophin BDNF resulted in further
significantly increased densities of beta-III-tubulin-positive cells in cultures
of spiral ganglia cells as compared with single treatments. In sum, Cr promoted
continuing propagation of rat inner ear-derived progenitor cells and supported
specifically in combination with BDNF the differentiation of neuronal cell types
from spiral ganglion-derived spheres.
PMID- 24356108
TI - Time-dependent changes in motor cortical excitability by electrical stimulation
combined with voluntary drive.
AB - Prolonged changes in primary motor cortex excitability in response to combined
neuromuscular electrical stimulation (NMES) and voluntary contraction with motor
evoked potentials (MEPs) were investigated by transcranial magnetic stimulation
and recorded by mechanomyography. Participants included 22 healthy individuals.
NMES was applied to the extensor carpi radialis (ECR) by voluntary ECR
contraction with 20% maximum voluntary contraction (MVC) of wrist extension. MEPs
were recorded from the flexor carpi radialis (FCR) and ECR at rest with NMES, at
20% MVC with NMES (combined), and at 20% MVC alone. Significant conditional
effects were revealed in ECR and FCR. In the combined condition, MEPs showed
gradual enhancement, and those in FCR were more inhibited than those in the
control condition. Voluntary contraction with NMES increased primary motor cortex
excitability in the agonist muscle, whereas the antagonist muscle might affect
reciprocal modulation in the combined condition.
PMID- 24356109
TI - Clinical features of a new acid-labile subunit (IGFALS) heterozygous mutation:
anthropometric and biochemical characterization and response to growth hormone
administration.
AB - BACKGROUND: Homozygous mutations in acid-labile subunit (IGFALS) gene result in
short stature, very low circulating levels of acid-labile subunit (ALS), insulin
growth factor 1 (IGF1) and insulin growth factor binding protein 3 (IGFBP3) and a
poor response to growth hormone (GH). The impact of IGFALS mutations
heterozygosity on growth is unknown. PATIENT AND METHODS: We describe a 10-year
old girl with severe short stature (height -3.2 SDS), heterozygous for a new
IGFALS mutation. RESULTS: The girl showed low circulating IGF1, IGFBP3 and ALS
levels and normal GH secretion. We found a novel heterozygous frameshift IGFALS
mutation (c.1283delA, p.Gln428Argfs*14). Size-exclusion chromatography showed a
reduction of the IGF1, IGFBP3 and ALS 150-kDa ternary complex (by about 55%)
compared to a control. An IGF-1 generation test, with two different GH dosages,
showed a good response in term of increase in IGF1 and in formation of the
ternary complex at size-exclusion chromatography. Clinical response after 6
months of therapy with GH was satisfactory (height velocity increased from 3 to 8
cm/year). CONCLUSION: We suggest that (1) heterozygous IGFALS mutations can be
responsible for a subset of patients with severe short stature (below -2.5 SDS),
low IGF1 (below -2 SDS) and normal GH secretion, and (2) the identification by
IGFALS molecular screening of this subset of patients could help in the
administration of the appropriate therapy.
PMID- 24356110
TI - Ubiquitous interplay between charge ordering and high-temperature
superconductivity in cuprates.
AB - Besides superconductivity, copper-oxide high-temperature superconductors are
susceptible to other types of ordering. We used scanning tunneling microscopy and
resonant elastic x-ray scattering measurements to establish the formation of
charge ordering in the high-temperature superconductor Bi2Sr2CaCu2O(8+x).
Depending on the hole concentration, the charge ordering in this system occurs
with the same period as those found in Y-based or La-based cuprates and displays
the analogous competition with superconductivity. These results indicate the
similarity of charge organization competing with superconductivity across
different families of cuprates. We observed this charge ordering to leave a
distinct electron-hole asymmetric signature (and a broad resonance centered at
+20 milli-electron volts) in spectroscopic measurements, indicating that it is
likely related to the organization of holes in a doped Mott insulator.
PMID- 24356111
TI - Physics Probing the electron.
PMID- 24356112
TI - Mating induces shrinking and death in Caenorhabditis mothers.
AB - Interactions between the germ line and the soma help optimize reproductive
success. We discovered a phenomenon linking reproductive status to longevity: In
both hermaphroditic and gonochoristic Caenorhabditis, mating leads to female
shrinking and death, compressing postreproductive life span. Male sperm induces
germline- and DAF-9/DAF-12-dependent shrinking, osmotic stress susceptibility,
and subsequent life-span decrease, whereas seminal fluid induces DAF-16-dependent
life-span decrease and fat loss. Our study provides insight into the
communication between males and the female germ line and soma to regulate
reproduction and longevity, revealing a high-reproduction, low-life-span state
induced by mating. Postmating somatic collapse may be an example of the sexually
antagonistic influence that males in many species exert on female behavior to
maximize their own reproductive success.
PMID- 24356113
TI - IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively
infected with HIV.
AB - The progressive depletion of quiescent "bystander" CD4 T cells, which are
nonpermissive to HIV infection, is a principal driver of the acquired
immunodeficiency syndrome (AIDS). These cells undergo abortive infection
characterized by the cytosolic accumulation of incomplete HIV reverse
transcripts. These viral DNAs are sensed by an unidentified host sensor that
triggers an innate immune response, leading to caspase-1 activation and
pyroptosis. Using unbiased proteomic and targeted biochemical approaches, as well
as two independent methods of lentiviral short hairpin RNA-mediated gene
knockdown in primary CD4 T cells, we identify interferon-gamma-inducible protein
16 (IFI16) as a host DNA sensor required for CD4 T cell death due to abortive HIV
infection. These findings provide insights into a key host pathway that plays a
central role in CD4 T cell depletion during disease progression to AIDS.
PMID- 24356114
TI - Order of magnitude smaller limit on the electric dipole moment of the electron.
AB - The Standard Model of particle physics is known to be incomplete. Extensions to
the Standard Model, such as weak-scale supersymmetry, posit the existence of new
particles and interactions that are asymmetric under time reversal (T) and nearly
always predict a small yet potentially measurable electron electric dipole moment
(EDM), d(e), in the range of 10(-27) to 10(-30) e.cm. The EDM is an asymmetric
charge distribution along the electron spin (S(->)) that is also asymmetric under
T. Using the polar molecule thorium monoxide, we measured d(e) = (-2.1 +/-
3.7stat +/- 2.5syst) * 10(-29) e.cm. This corresponds to an upper limit of |d(e)|
< 8.7 * 10(-29) e.cm with 90% confidence, an order of magnitude improvement in
sensitivity relative to the previous best limit. Our result constrains T
violating physics at the TeV energy scale.
PMID- 24356115
TI - Charge order driven by Fermi-arc instability in Bi2Sr(2-x)La(x)CuO(6+delta).
AB - The understanding of the origin of superconductivity in cuprates has been
hindered by the apparent diversity of intertwining electronic orders in these
materials. We combined resonant x-ray scattering (REXS), scanning-tunneling
microscopy (STM), and angle-resolved photoemission spectroscopy (ARPES) to
observe a charge order that appears consistently in surface and bulk, and in
momentum and real space within one cuprate family, Bi2Sr(2-x)La(x)CuO(6+delta).
The observed wave vectors rule out simple antinodal nesting in the single
particle limit but match well with a phenomenological model of a many-body
instability of the Fermi arcs. Combined with earlier observations of electronic
order in other cuprate families, these findings suggest the existence of a
generic charge-ordered state in underdoped cuprates and uncover its intimate
connection to the pseudogap regime.
PMID- 24356116
TI - Scintigraphic evaluation of osseointegrative response around calcium phosphate
coated titanium implants in tibia bone: effect of platelet-rich plasma on bone
healing in dogs.
AB - Differential diagnoses for canine bone disease are commonly based on radiography.
However, scintigraphy is a nuclear scanning test to trace bone healing during
stress fracture and osteomyelitis and thus can be used to probe the
osseointegration process in vivo in the context of the dental implant. The
purpose of this study was to explore the possibility of using noninvasive
scintigraphy to probe the effect of platelet-rich plasma (PRP) to enhance
osseointegration of the implant and to confirm the result with a parallel
histological examination in adult beagle dogs. Two independent calcium phosphate
coated titanium screw implants 8 mm in length and 4 mm in diameter were inserted
into each tibia in 4 dogs (4 implants/animal, total = 16). The PRP-treated group
was deposited with 0.5 ml of PRP into the drill hole in the right tibia; the
control group was instilled with 0.5 ml of saline into the drill hole in the left
counterpart before titanium screw implantation. Radiography of the implanted
tibias showed complete osseointegration but no osteomyelitis. No difference in
the ossification of the peri-implant bone on the radiographs was observed between
the two groups during the experimental period. However, the scintigraphic
findings revealed obvious differences in bone uptake between the two groups. The
higher bone uptake in the PRP-treated group significantly increased bone activity
and faster bone regeneration compared to the control group (p < 0.05) at 4 weeks
after implantation. The percentage of the bone-to-implant contact on histological
examination in the PRP-treated group showed dense cortical bone formation in
close contact with the metallic surface of the titanium implant (p < 0.05).
Quantitative histological analysis correlated well with that of the scintigraphic
evaluation as revealed by Pearson correlation analysis (r = 0.72, p < 0.05).
Thus, scintigraphy is a sensitive and noninvasive method suitable for
osseointegration of the implant in vivo.
PMID- 24356117
TI - Caveat emptor: single nucleotide polymorphism reporting in pharmacogenomics.
AB - While it is arguably the most comprehensive source of genetic information, the
NCBI's dbSNP database (National Center for Biotechnology Information database of
single nucleotide polymorphisms; http://www.ncbi.nlm.nih.gov/projects/SNP/) is
imperfect. In this commentary, we highlight the issues surrounding this database,
while considering the great importance and utility of this resource for those in
the pharmacology and pharmacogenomics communities. We describe our experience
with the information in this database as a cautionary tale for those who will
utilize such information in the future. We also discuss several measures that
could render it more reliable.
PMID- 24356118
TI - Solved? The reductive radiation chemistry of alanine.
AB - The structural changes throughout the entire reductive radiation-induced pathway
of l-alpha-alanine are solved on an atomistic level with the aid of periodic DFT
and nudged elastic band (NEB) simulations. This yields unprecedented information
on the conformational changes taking place, including the protonation state of
the carboxyl group in the "unstable" and "stable" alanine radicals and the
internal transformation converting these two radical variants at temperatures
above 220 K. The structures of all stable radicals were verified by calculating
EPR properties and comparing those with experimental data. The variation of the
energy throughout the full radiochemical process provides crucial insight into
the reason why these structural changes and rearrangements occur. Starting from
electron capture, the excess electron quickly localizes on the carbon of a
carboxyl group, which pyramidalizes and receives a proton from the amino group of
a neighboring alanine molecule, forming a first stable radical species (up to 150
K). In the temperature interval 150-220 K, this radical deaminates and
deprotonates at the carboxyl group, the detached amino group undergoes inversion
and its methyl group sustains an internal rotation. This yields the so-called
"unstable alanine radical". Above 220 K, triggered by the attachment of an
additional proton on the detached amino group, the radical then undergoes an
internal rotation in the reverse direction, giving rise to the "stable alanine
radical", which is the final stage in the reductive radiation-induced decay of
alanine.
PMID- 24356122
TI - Recalling good memories.
PMID- 24356124
TI - Universal binding energy relation for cleaved and structurally relaxed surfaces.
AB - The universal binding energy relation (UBER), derived earlier to describe the
cohesion between two rigid atomic planes, does not accurately capture the
cohesive properties when the cleaved surfaces are allowed to relax. We suggest a
modified functional form of UBER that is analytical and at the same time
accurately models the properties of surfaces relaxed during cleavage. We
demonstrate the generality as well as the validity of this modified UBER through
first-principles density functional theory calculations of cleavage in a number
of crystal systems. Our results show that the total energies of all the relaxed
surfaces lie on a single (universal) energy surface, that is given by the
proposed functional form which contains an additional length-scale associated
with structural relaxation. This functional form could be used in modelling the
cohesive zones in crack growth simulation studies. We find that the cohesive law
(stress-displacement relation) differs significantly in the case where cracked
surfaces are allowed to relax, with lower peak stresses occurring at higher
displacements.
PMID- 24356123
TI - Modulation of HERG K+ channels by chronic exposure to activators and inhibitors
of PKA and PKC: actions independent of PKA and PKC phosphorylation.
AB - BACKGROUND: Human ether-a-go-go-related gene (HERG) channel is the major
molecular component of the native rapid delayed rectifier K(+) current (IKr) that
is a crucial determinant of cardiac repolarization. Impairment of IKr/HERG
function is commonly believed to be a mechanism causing long QT syndromes (LQTS),
a lethal ventricular tachyarrhythmia. The cAMP-dependent protein kinase A (PKA)
and PKC activities are markedly increased in some pathological conditions of the
heart such as heart failure. This study was designed to investigate the effects
of acute and chronic exposure to PKA or PKC activators and inhibitors on HERG
channel activities and to provide insight into the mechanisms for the
modulations. METHODS: Channel activity was measured in HEK293 cells stably
expressing HERG using whole-cell patch-clamp techniques. Intracellular reactive
oxygen species (ROS) were measured by CM-H2DFDA. Mitochondrial membrane potential
(DeltaPsim) was measured using JC-1 dye. HERG channel phosphorylation was assayed
by [(32)P]orthophosphate methods. RESULTS: Acute exposure of cells to PKA or PKC
activators by bath superfusion minimally affected IHERG, and so did the PKA or
PKC inhibitor. By comparison, prolonged exposure (chronic incubation) of cells to
PKA or PKC activators significantly impaired HERG K(+) channel function as
reflected by reduced IHERG density and positive shift of the steady-state
activation curve. Antioxidants vitamin E and MnTBAP both abolished the depressive
effects of PKA or PKC activators on HERG function. Further, both PKA and PKC
activators stimulated production of intracellular reactive oxygen species (ROS),
an effect efficiently prevented by antioxidants or by PKA and PKC inhibitors.
CONCLUSIONS: HERG function is insensitive to PKA or PKC phosphorylation
modulation per se, but can be impaired by the activators of PKA or PKC with long
exposure likely via generation of ROS. In view of the critical role of HERG K(+)
channel in regulating cardiac repolarization and the sustained activation of both
PKA and PKC in many pathological conditions of the heart such as heart failure,
it is conceivable that HERG impairment by ROS accumulation induced by PKA and PKC
contributes to the impaired cardiac repolarization.
PMID- 24356125
TI - Genomic imprinting and maternal effect genes in haplodiploid sex determination.
AB - The research into the Drosophila melanogaster sex-determining system has been at
the basis of all further research on insect sex determination. This further
research has made it clear that, for most insect species, the presence of
sufficient functional Transformer (TRA) protein in the early embryonic stage is
essential for female sexual development. In Hymenoptera, functional analysis of
sex determination by knockdown studies of sex-determining genes has only been
performed for 2 species. The first is the social insect species Apis mellifera,
the honeybee, which has single-locus complementary sex determination (CSD). The
other species is the parasitoid Nasonia vitripennis, the jewel wasp. Nasonia has
a non-CSD sex-determining system, described as the maternal effect genomic
imprinting sex determination system (MEGISD). Here, we describe the arguments
that eventually led to the formulation of MEGISD and the experimental data that
supported and refined this model. We evaluate the possibility that DNA
methylation lies at the basis of MEGISD and briefly address the role of genomic
imprinting in non-CSD sex determination in other Hymenoptera.
PMID- 24356127
TI - Dengue outbreaks: a constant risk for Reunion Island. Results from a
seroprevalence study among blood donors.
AB - BACKGROUND: Immunity against dengue virus (DENV) on Reunion Island could play an
important role in the risk of dengue outbreaks but is rather unknown. A study was
performed to estimate seroprevalence of antibodies against DENV among blood
donors. METHODS: An age- and sex-stratified sample of 1825 sera was randomly
selected. RESULTS: Overall seroprevalence was 3.1% (95% CI: 2.2-3.9%);
seroprevalence increased with age and was much higher in women than in men.
CONCLUSION: The low level of herd immunity is consistent with the absence of an
endemic circulation of DENV, and makes it probable that Reunion Island will face
future outbreaks.
PMID- 24356128
TI - [New challenges in multiple sclerosis treatment].
PMID- 24356129
TI - [HIV-associated cognitive disorders: tat perturbs neurosecretion].
PMID- 24356130
TI - [Moderation in all things: p53 deregulation, cancer and telomere syndromes].
PMID- 24356131
TI - [Lymphatic valve morphogenesis].
PMID- 24356132
TI - [Transcriptome complexity in germ cells].
PMID- 24356133
TI - [Influence of PD-1 on the immunological synapse: a facet of immune regulation ?].
PMID- 24356134
TI - [Leukotriene B(4): a lipid at the heart of inflammation].
PMID- 24356135
TI - [Red blood cell, a new player in the pathophysiology of Gaucher disease].
PMID- 24356136
TI - [Mechanics and cell division: temporal control of abscission].
PMID- 24356137
TI - [Mutations in succinate dehydrogenase and DNA methylation].
PMID- 24356138
TI - [Apoptosis and AIDS, a question of integration?].
PMID- 24356139
TI - [shrIL1R2, a potential candidate to treat endometriosis].
PMID- 24356140
TI - [New and emerging treatments for multiple sclerosis].
AB - A number of disease-modifying therapies have been recently approved for the
treatment of multiple sclerosis (MS). These molecules which prevent relapses and
new central nervous system lesions are more efficient than the "old" first line
therapies and/or more convenient, especially with oral agents. Their usefulness
in treating active MS is undeniable, but we have to be aware of their potentially
extremely severe side effects. The treatment algorithm in MS is constantly
evolving according to the long term safety profile of these new treatments. A
better knowledge of fundamental pathophysiology is associated with the
development of new molecules targeting the immunological cascade of the disease
as well as the mechanisms promoting remyelination and repair.
PMID- 24356141
TI - [The obsessive compulsive disorder].
AB - The obsessive compulsive disorder (OCD) is a frequent disease with a high
comorbidity. The usual treatment is a combination of pharmacological and
psychotherapeutic treatment. However, 30% of patients still have persistent and
severe symptoms, with an important functional impact. These last years, the
integration of the new neuroanatomical, neurochemical, neuropsychological,
genetic and phenomenological data, allows a better understanding of the
physiopathology and the development of new treatments for OCD, as neuromodulation
for the severe and refractory cases.
PMID- 24356142
TI - [Programmed cell death comes in many flavors].
AB - Apoptosis is nowadays what comes first to your scientist mind when someone
mentions cellular suicide. However this is not the sole form of programmed cell
death and many other alternative or atypical pathways have now been described.
These pathways are indeed rather preferred to apoptosis in some instances based
on tissue origin, cell type or development stage of the target cell. In this
review, we describe many different programmed cell death subtypes according to
their characteristics. Discrete, brutal, final or singular cell death pathways
all participate in the elimination of unwanted, damaged or dangerous cells in
organisms hence contributing to our knowledge of this particular feature of
living beings: dying! Through description of anoikis, necroptosis, entosis,
netosis, pyroptosis or ferroptosis, we have no choice but to realize that
programmed cell death comes in many flavors.
PMID- 24356143
TI - [Role of the p53 tumor suppressor in metabolism].
AB - The p53 tumor suppressor is an essential downstream effector of various cellular
stress response pathways that is functionally inactivated in most, if not all,
tumors. Since its discovery more than 30 years ago, its role in the control of
cell proliferation, senescence and cell survival has been widely described.
However, growing evidences from several laboratories indicate that p53 has
important transcriptional and non-transcriptional functions in the control of
metabolism, including the regulation of glycolysis, glutaminolysis or
mitochondrial respiration. Originally identified using in vitro cellular models,
this previously underestimated role of p53 has been confirmed in vivo in various
genetically engineered mouse models. These recent data suggest that p53 functions
in various metabolic pathways significantly contribute to its role in adult
tissue homeostasis, aging as well as tumor suppression.
PMID- 24356144
TI - [Role of thrombospondin-1 in the development of kidney diseases].
AB - Thrombospondin-1 (TSP-1) is a 450-kDa matricellar glycoprotein. By its various
domains, it can interact with various partners and exhibit anti-angiogenic, pro
apoptotic and immunomodulatory activities. TSP-1 is also a major endogenous
activator of the pro-fibrotic growth factor TGF-beta. In healthy adult renal
parenchyma, TSP-1 expression is very scarce and limited to Bowman's capsule and
interstitium. During nephropathies, many cell types can express or secrete TSP-1
(mesangial, endothelial, smooth muscle, tubular cells, podocytes and fibroblasts)
depending on the nature of injury and the evolutive stage of the disease.
Inhibition of the different domains of TSP-1 using specific antibodies or
peptides, blockade of TSP-1 expression by antisense oligonucleotides and use of
knock-out mice, allowed to identify the role of TSP-1 in various models of
experimental nephropathy. All these studies demonstrated a deleterious effect of
TSP-1 on renal repair by inducing TGF-beta and fibrosis, decreasing VEGF and
capillary density, and enhancing inflammatory cells recruitment. Thus, TSP-1
represents a potential therapeutic target for the management of chronic kidney
diseases.
PMID- 24356145
TI - [RTEL1 (regulator of telomere elongation helicase 1), a DNA helicase essential
for genome stability].
AB - RTEL1 (regulator of telomere length helicase 1) is a DNA helicase that has been
identified more than 10 years ago. Many works since, mainly in the nematode
Caenorhabditis elegans and the mouse, have highlighted its role in chromosomal
stability, maintenance of telomere length, and DNA repair. Recently, four
laboratories have characterized RTEL1 mutations in patients with dyskeratosis
congenita (DC) and Hoyeraal-Hreidarsson (HH) syndrome, a rare and severe variant
of DC. We here summarize the current knowledge on RTEL1 and discuss the possible
other functions that RTEL1 could play.
PMID- 24356146
TI - [Epithelial cell in intestinal homeostasis and inflammatory bowel diseases].
AB - Crohn's disease (CD) and ulcerative colitis (UC) are the principal inflammatory
bowel diseases (IBD) which physiopathology is currently poorly elucidated. During
these diseases, the participation of the epithelial cell in the installation and
the perpetuation of the intestinal inflammation is now clearly implicated. In
fact, the intestinal epithelium located at the interface between the internal
environment and the intestinal luminal, is key to the homeostatic regulation of
the intestinal barrier. This barrier can schematically be regarded as being three
barriers in one: a physical, chemical and immune barrier. The barrier function of
epithelial cell can be altered by various mechanisms as occurs in IBD. The goal
of this article is to review the literature on the role of the epithelial cell in
intestinal homeostasis and its implication in the IBD.
PMID- 24356147
TI - [Leishmania epidemiology, diagnosis, chemotherapy and vaccination approaches in
the international network of Pasteur Institutes].
AB - Protozoan parasites of the genus Leishmania generate severe human diseases termed
leishmaniases. Due to their frequency and the severity of certain clinical forms,
these diseases represent a major public health problem and limit the economic
growth in various developing countries. The presence of Pasteur Institutes in
countries with endemic leishmaniasis has provided important incentives to develop
a strong public health agenda in the Pasteur scientific community with respect to
this important disease. A concerted effort is now coordinated through the
recently created LeishRIIP platform (www.leishriip.org), which aims to identify
synergies and complementary expertise between the eleven members of the
international network of Pasteur Institutes working on various aspects of the
disease including epidemiology, diagnosis, chemotherapy and vaccination.
PMID- 24356148
TI - [Age for HPV vaccination: recommandations from the French high council of public
health].
AB - The French high council of public health has recently amended age for HPV
vaccination. The paper will describe reasons that have contributed to the
development of these new guidelines. Parental and adolescent acceptance of HPV
vaccination is reported as well as potential barriers among medical practices.
First results of immunogenicity of vaccines using alternative dosing schedules
are presented. Finally, preliminary data on clinical efficacy of the quadrivalent
vaccine on genital warts and cervical precancerous lesions are presented. A
decrease in the prevalence of infection with genotypes included in the vaccine
has now been reported in several studies. This decrease may be partly
attributable to herd immunity.
PMID- 24356149
TI - [A surprising commercial success].
AB - Direct-to-consumer (DTC) genetic tests have become quite popular in the USA. This
article explores the uses to which they are put and the motivations of the
customers.
PMID- 24356150
TI - Plagiarism is plagiarism is plagiarism.
PMID- 24356151
TI - Whose words in the textbook?
PMID- 24356152
TI - Yes, it's plagiarism, but it's complicated.
PMID- 24356153
TI - Anesthesia and cancer recurrence: improved understanding, but no reason for
change.
PMID- 24356154
TI - Search and rescue: think globally and act locally.
PMID- 24356155
TI - Nitrous oxide for labor pain: is it a laughing matter?
PMID- 24356156
TI - Anesthesia scholarship, research, and publication.
PMID- 24356157
TI - Guidelines for performing a comprehensive transesophageal echocardiographic
examination: recommendations from the American Society of Echocardiography and
the Society of Cardiovascular Anesthesiologists.
PMID- 24356158
TI - Transesophageal echocardiography examination for percutaneous right ventricular
assist device placement.
PMID- 24356159
TI - Use of intraoperative transesophageal echocardiography to evaluate positioning of
TandemHeart(r) percutaneous right ventricular assist device cannulae.
PMID- 24356160
TI - Turbulence in the left ventricular outflow tract caused by an eccentric mitral
inflow jet masquerades as aortic regurgitation.
PMID- 24356161
TI - Clot in bovine arch diagnosed by transesophageal echocardiography.
PMID- 24356162
TI - Consensus guidelines for the management of postoperative nausea and vomiting.
AB - The present guidelines are the most recent data on postoperative nausea and
vomiting (PONV) and an update on the 2 previous sets of guidelines published in
2003 and 2007. These guidelines were compiled by a multidisciplinary
international panel of individuals with interest and expertise in PONV under the
auspices of the Society for Ambulatory Anesthesia. The panel members critically
and systematically evaluated the current medical literature on PONV to provide an
evidence-based reference tool for the management of adults and children who are
undergoing surgery and are at increased risk for PONV. These guidelines identify
patients at risk for PONV in adults and children; recommend approaches for
reducing baseline risks for PONV; identify the most effective antiemetic single
therapy and combination therapy regimens for PONV prophylaxis, including
nonpharmacologic approaches; recommend strategies for treatment of PONV when it
occurs; provide an algorithm for the management of individuals at increased risk
for PONV as well as steps to ensure PONV prevention and treatment are implemented
in the clinical setting.
PMID- 24356163
TI - Noninvasive monitoring of lung recruitment maneuvers in morbidly obese patients:
the role of pulse oximetry and volumetric capnography.
AB - BACKGROUND: We conducted this study to determine whether pulse oximetry and
volumetric capnography (VCap) can determine the opening and closing pressures of
lungs of anesthetized morbidly obese patients. METHODS: Twenty morbidly obese
patients undergoing laparoscopic bariatric surgery with capnoperitoneum were
studied. A lung recruitment maneuver was performed in pressure control
ventilation as follows: (1) During an ascending limb, the lungs' opening pressure
was detected. After increasing positive end-expiratory pressure (PEEP) from 8 to
16 cm H2O, fraction of inspired oxygen (FIO2) was decreased until pulse oximetric
arterial saturation (SpO2) was <92%. Thereafter, end-inspiratory pressure was
increased in steps of 2 cm H2O, from 36 to a maximum of 50 cm H2O. The opening
pressure was attained when SpO2 exceeded 97%. (2) During a subsequent decreasing
limb, the lungs' closing pressure was identified. PEEP was decreased from 22 to
10 cm H2O in steps of 2 cm H2O. The closing pressure was determined as the PEEP
value at which respiratory compliance decreased from its maximum value. We
continuously recorded lung mechanics, SpO2, and VCap. RESULTS: The lungs' opening
pressures were detected at 44 (4) cm H2O (median and interquartile range) and the
closing pressure at 14 (2) cm H2O. Therefore, the level of PEEP that kept the
lungs without collapse was found to be 16 (3) cm H2O. Using respiratory
compliance as a reference, receiver operating characteristic analysis showed that
SpO2 (area under the curve [AUC] 0.80 [SE 0.07], sensitivity 0.65, and
specificity 0.94), the elimination of CO2 per breath (AUC 0.91 [SE 0.05],
sensitivity 0.85, and specificity 0.98), and Bohr's dead space (AUC 0.83 [SE
0.06], sensitivity 0.70, and specificity 0.95] were relatively accurate for
detecting lung collapse during the decreasing limb of a recruitment maneuver.
CONCLUSIONS: Lung recruitment in morbidly obese patients could be effectively
monitored by combining noninvasive pulse oximetry and VCap. SpO2, the elimination
of CO2, and Bohr's dead space detected the individual's opening and closing
pressures.
PMID- 24356164
TI - Time-delay when updating infusion rates in the Graseby 3400 pump results in
reduced drug delivery.
AB - Infusion pumps are commonly used for infusion of drugs for physiologic control,
and infusion rate has been demonstrated to affect the parameters of
pharmacokinetic models. In attempting to develop a model that explained this
behavior, we examined the behavior of the Graseby 3400 syringe pump under a range
of flow conditions and with variations in syringe characteristics. Two issues
were identified: start-up loss (the difference between actual and ideal delivery
on initial infusion) and update loss (the difference between actual and ideal
delivery when transmitting a command to change infusion rate). Under worst-case
conditions, this may result in a 20-second period of zero delivery during start
up, and when updating infusion rates once per second, zero output. These effects
are influenced by syringe characteristics and vary sufficiently as to make it
impossible to isolate this effect from the pharmacokinetic process being
controlled. The implications of this for previous published results and clinical
application of target-controlled infusions are discussed.
PMID- 24356165
TI - Nitrous oxide for the management of labor pain: a systematic review.
AB - BACKGROUND: We systematically reviewed evidence addressing the effectiveness of
nitrous oxide for the management of labor pain, the influence of nitrous oxide on
women's satisfaction with their birth experience and labor pain management, and
adverse effects associated with nitrous oxide for labor pain management. METHODS:
We searched the MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied
Health Literature (CINAHL) databases for articles published in English. The study
population included pregnant women in labor intending a vaginal birth, birth
attendees or health care providers who may be exposed to nitrous oxide during
labor, and the fetus/neonate. RESULTS: We identified a total of 58 publications,
representing 59 distinct study populations: 2 studies were of good quality, 11
fair, and 46 poor. Inhalation of nitrous oxide provided less effective pain
relief than epidural analgesia, but the quality of studies was predominately
poor. The heterogeneous outcomes used to assess women's satisfaction with their
birth experience and labor pain management made synthesis of studies difficult.
Most maternal adverse effects reported in the literature were unpleasant side
effects that affect tolerability, such as nausea, vomiting, dizziness, and
drowsiness. Apgar scores in newborns whose mothers used nitrous oxide were not
significantly different from those of newborns whose mothers used other labor
pain management methods or no analgesia. Evidence about occupational harms and
exposure was limited. CONCLUSIONS: The literature addressing nitrous oxide for
the management of labor pain includes few studies of good or fair quality.
Further research is needed across all of the areas examined: effectiveness,
satisfaction, and adverse effects.
PMID- 24356166
TI - A randomized controlled comparison between combined spinal-epidural and single
shot spinal techniques in morbidly obese parturients undergoing cesarean
delivery: time for initiation of anesthesia.
AB - BACKGROUND: There is no current consensus on the optimal technique for
subarachnoid anesthesia in morbidly obese parturients even though some providers
prefer the combined spinal-epidural (CSE) over single-shot spinal (SSS)
technique. In this randomized controlled study, we compared the time required for
initiation of subarachnoid anesthesia between SSS and CSE techniques in morbidly
obese parturients undergoing elective cesarean delivery. METHODS: Morbidly obese
parturients presenting for elective cesarean delivery were randomized to receive
subarachnoid anesthesia performed either with a SSS or a CSE technique. The
spinal procedure in the sitting position was attempted by an experienced resident
for up to 10 minutes, and if unsuccessful, the attending obstetric
anesthesiologist assumed control of the procedure. The primary outcome was the
time it took from the insertion of the introducer needle (SSS group) or insertion
of the epidural needle (CSE group) to the end of intrathecal injection of drugs
(procedure time). RESULTS: Forty-four patients were enrolled and completed the
study. Three were excluded due to protocol violations. Of the remaining, 21
patients were in the SSS group and 20 in the CSE group. Demographic variables and
mean (SD) body mass index (48.7 +/- 7.6 kg/m for SSS; 49.9 +/- 8.6 kg/m for CSE)
were not different between groups. The median [interquartile range] for procedure
time was 210 [116-692] seconds and 180 [75-450] seconds for SSS and CSE groups,
respectively (P = 0.36), while the 95% confidence interval (CI) of the difference
was -80 to +180 seconds. The first operator completed the procedure in <10
minutes in 71% of subjects in the SSS group and 95% of those in the CSE group (P
= 0.09) and the 95% CI of the difference was -2% to +45%. There were more
attempts to successful completion of the procedure in the SSS group (P = 0.007)
with its 95% CI of the difference being +1 to +6. CONCLUSION: Our results suggest
that the CSE technique is noninferior to the SS technique in morbidly obese
parturients for time of initiation of subarachnoid anesthesia and may be
accomplished with fewer attempts than the SSS technique with experienced
residents.
PMID- 24356167
TI - Brain electrical activity obeys Benford's law.
AB - BACKGROUND: Monitoring and automated online analysis of brain electrical activity
are frequently used for verifying brain diseases and for estimating anesthetic
depth in subjects undergoing surgery. However, false diagnosis with potentially
catastrophic consequences for patients such as intraoperative awareness may
result from unnoticed irregularities in the process of signal analysis. Here we
ask whether Benford's Law can be applied to detect accidental or intended
modulation of neurophysiologic signals. This law states that the first digits of
many datasets such as atomic weights or river lengths are distributed
logarithmically and not equally. In particular, we tested whether data obtained
from electrophysiological recordings of human patients representing global
activity and organotypic slice cultures representing pure cortical activity
follow the predictions of Benford's Law in the absence and in the presence of an
anesthetic drug. METHODS: Electroencephalographic (EEG) recordings from human
subjects and local field potential recordings from cultured cortical brain slices
were obtained before and after administration of sevoflurane. The first digit
distribution of the datasets was compared with the Benford distribution. RESULTS:
All datasets showed a Benford-like distribution. Nevertheless, distributions
belonging to different anesthetic levels could be distinguished in vitro and in
human EEGs. With sevoflurane, the first digit distribution of the in vitro data
becomes steeper, while it flattens for EEG data. In the presence of high
frequency noise, the Benford distribution falls apart. CONCLUSIONS: In vitro and
EEG data show a Benford-like distribution which is altered by sevoflurane or
destroyed by noise used to simulate artefacts. These findings suggest that
algorithms based on Benford's Law can be successfully used to detect sevoflurane
induced signal modulations in electrophysiological recordings.
PMID- 24356168
TI - Epidural lysis of adhesions for failed back surgery and spinal stenosis: factors
associated with treatment outcome.
AB - BACKGROUND: Failed back surgery syndrome (FBSS) is a challenging problem. One
treatment advocated to treat FBSS is epidural lysis of adhesions (LOA). The
results of studies examining LOA for FBSS have been mixed, but are limited
because no study has ever sought to identify factors associated with outcomes.
METHODS: We performed this multicenter, retrospective study in 115 patients who
underwent LOA for FBSS (n = 104) or spinal stenosis (n = 11) between 2004 and
2007. Twenty-seven demographic, clinical, and procedural variables were extracted
from medical records and correlated with the outcome, defined as >=50% pain
relief lasting >=1 month. Univariable analysis was performed, followed by
multivariable logistic regression. RESULTS: Overall, 48.7% (95% confidence
interval [CI], 39.3%-58.1%) of patients experienced a positive outcome. In
univariable analysis, those who had a positive outcome were older (mean age 64.1
years; 95% CI, 59.7-68.6 vs 57.2; 95% CI, 53.0-61.4 years; P = 0.02), while
higher baseline numerical rating scale pain scores were associated with a
negative outcome (mean 6.7 years; 95% CI, 6.0-7.3 vs 7.5; 95% CI, 6.9-8.0; P =
0.07). Use of hyaluronidase did not correlate with outcomes in univariable
analysis (odds ratio [OR], 1.2; 95% CI, 0.6-2.5; P = 0.65). In multivariable
analysis, age >=81 years (OR, 7.8; 95% CI, 1.4-53.7), baseline numerical rating
scale score <=9 (OR, 4.4; 95% CI, 1.4-16.3, P = 0.02), and patients on or seeking
disability or worker's compensation (OR, 4.4; 95% CI, 1.1-19.5, P = 0.04) were
significantly more likely to experience a positive outcome. CONCLUSIONS:
Considering our modest success rate, selecting patients for epidural LOA based on
demographic and clinical factors may help better select treatment candidates.
Procedural factors such as the use of hyaluronidase that increase risks and costs
did not improve outcomes, so further research is needed before these become
standard practice.
PMID- 24356169
TI - Safety of interlaminar and transforaminal epidural steroid injections.
PMID- 24356170
TI - In response.
PMID- 24356171
TI - Intraarticular steroids versus radiofrequency denervation of lumbar facets for
treatment of low back pain.
PMID- 24356172
TI - Intraarticular lumbar facet joint steroid injections and lumbar facet joint
radiofrequency denervation.
PMID- 24356173
TI - Noninvasive cardiac output monitoring with Nexfin: we really need impact studies.
PMID- 24356174
TI - In response.
PMID- 24356175
TI - A newly modified hemoglobin H inclusion test as a secondary screening for
alpha(0)-thalassemia in Southeast Asian populations.
AB - Screening for alpha(0)-thalassemia is usually associated with a high false
positive rate, leading to an unnecessary PCR workload for accurate diagnosis. We
have developed a modified Hb H inclusion test for use as a secondary screening.
This test was performed on young red blood cell enriched fractions using dextran
sedimentation. The study was performed in 100 subjects positive on initial
screening. Confirmatory tests included Hb analysis and a multiplex PCR assay to
identify alpha(0)-thalassemia deletions. A modified Hb H inclusion test was
positive in 31 cases, 30 of whom were alpha(0)-thalassemia carriers (97%). The
remaining case (3.0%) was homozygous for alpha(+)-thalassemia. The remaining 69
cases with a negative Hb H inclusion test included normal subjects, alpha(+)
thalassemia carriers and beta-thalassemia carriers. Two of them (2/69, 3.0%) were
found to be double heterozygotes for beta(0)-thalassemia and alpha(0)
thalassemia. The overall sensitivity and specificity of the modified Hb H
inclusion test for screening of alpha(0)-thalassemia were 94.0 and 99.0%,
respectively. Therefore, we recommend the use of this test in combination with Hb
analysis to exclude cases with alphabeta-thalassemia. This should lead to a
significant reduction in the number of cases referred for PCR analysis of
alpha(0)-thalassemia by about 50.0%.
PMID- 24356176
TI - Persisting hypoxaemia is an insufficient measure of adverse lung function in very
immature infants.
AB - BACKGROUND: Bronchopulmonary dysplasia (BPD), defined as protracted neonatal
hypoxaemia, is considered a risk factor for respiratory disease in adulthood. The
relationship between this diagnosis and the actual lung injury appearing in very
immature infants is, however, unknown. OBJECTIVES: To compare lung function at
term in very immature infants and full-term infants, and to determine how degree
and duration of neonatal hypoxaemia are related to other aspects of lung
function. DESIGN AND METHODS: All surviving, consecutive infants with gestational
age below 28 weeks from a geographically defined area were eligible. The alveolar
arterial oxygen pressure difference was assessed as a measure of oxygenation
failure. At term, functional residual capacity and gas-mixing efficiency were
measured by multiple-breath nitrogen washout, and compliance and conductance of
the respiratory system by the occlusion method. The results were compared to
those in 50 full-term controls. MAIN RESULTS: Thirty-seven of 46 eligible infants
were included. The preterm infants differed markedly from the full-term infants
in all lung functions tested. Infants diagnosed as having BPD had more
compromised lung function than those without, but the latter group differed
markedly from the full-term group in functional residual capacity, compliance and
gas-mixing efficiency. Only the mechanical variables were correlated to
hypoxaemia at 36 weeks postmenstrual age (PMA). CONCLUSIONS: Infants with
gestational age below 28 weeks at birth have remarkably impaired lung function at
term, regardless of whether they carry the diagnosis BPD or not. All very
immature infants may be at risk of future respiratory disease and should be
monitored appropriately.
PMID- 24356177
TI - Examining the effects of a targeted noise reduction program in a neonatal
intensive care unit.
AB - OBJECTIVES: To determine whether implementation of a noise reduction policy
followed by the addition of direct audit and feedback reduces noise levels in a
tertiary-level neonatal intensive care unit (NICU). STUDY DESIGN: Noise level
data was collected in three phases: (1) baseline (preintervention), (2)
immediately postimplementation of our noise reduction policy, (3) postunveiling
of direct audit and feedback mechanism. SETTING: A level 3 NICU in Ontario,
Canada. INTERVENTIONS: Noise reduction policy and a direct audit and feedback
mechanism. MAIN OUTCOME MEASURES: Average noise level. RESULTS: The baseline
level of noise in our unit consistently exceeds guidelines with an average
baseline noise of 49 dB (+/-1.4). Our intervention resulted in a significant
reduction in noise levels for one of the four areas in our NICU [-1.06 dB (-1.52,
-0.6)], with a trend towards reduction in a second area (-0.21 dB (-0.6, 0.18)).
Unexpectedly, two other areas experienced a significant increase in noise (2.05
dB (1.18, 2.94); 0.85 dB (0.11, 1.59)). CONCLUSIONS: The baseline noise in the
NICU consistently exceeds guidelines, but reductions in noise levels are
achievable. Nonetheless, more work is needed to find the optimal NICU design and
noise reduction strategy.
PMID- 24356178
TI - The trouble with informed consent.
PMID- 24356179
TI - Migrating granulomatous chronic reaction from hyaluronic acid skin filler
(Restylane): review and histopathological study with histochemical stainings.
AB - BACKGROUND: A unique case is presented in whom an allergic reaction to Restylane
filler, associated with migrating granulomas, persisted despite medical
interventions. A histopathological study was requested for evidence at court.
METHODS: Hematoxylin-eosin, alcian blue and colloidal iron staining were applied
to skin sample biopsies obtained 5 months and 3 years after the hyaluronic acid
(HA) injection. RESULTS: The histological staining highlighted the presence of
the filler inside the foreign body granuloma and in the derma of a biopsy
obtained after 5 months; a small amount of filler was discovered within a
granulomatous reaction 3 years after the injection. CONCLUSIONS: Smaller
fragments of HA display inflammatory, angiogenic and immune-stimulatory
activities. Intradermal skin testing before the start of HA filler therapy, and
before each subsequent injection, may prevent legal implications for the plastic
surgeon. Informed consent to skin tests should be obtained.
PMID- 24356181
TI - Male courtship vibrations delay predatory behaviour in female spiders.
AB - During courtship, individuals transfer information about identity, mating status
and quality. However, male web-building spiders face a significant problem: how
to begin courting female spiders without being mistaken for prey? Male Argiope
spiders generate distinctive courtship vibrations (shudders) when entering a
female's web. We tested whether courtship shudders delay female predatory
behaviour, even when live prey is present in the web. We presented a live cricket
to females during playbacks of shudder vibrations, or white noise, and compared
female responses to a control in which we presented a live cricket with no
playback vibrations. Females were much slower to respond to crickets during
playback of shudder vibrations. Shudder vibrations also delayed female predatory
behaviour in a related spider species, showing that these vibrations do not
simply function for species identity. These results suggest that male web
building spiders employ a phylogenetically conserved vibratory signal to
ameliorate the risk of pre-copulatory cannibalism.
PMID- 24356180
TI - Systemic thrombolysis for cerebral venous and dural sinus thrombosis: a
systematic review.
AB - BACKGROUND: The use of thrombolytics is frequently considered in patients with
cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite
anticoagulant therapy. PURPOSE: To collect all the published information about
the use of systemic thrombolysis in CVT in order to assess its efficacy and
safety. METHODS: We performed a PubMed search, checked all reference lists of
studies found and used data from the International Study on Cerebral Vein and
Dural Sinus Thrombosis (ISCVT). Outcome was classified at the last available
follow-up by the modified Rankin Scale (mRS). The cases were stratified according
to variables that might influence outcome. RESULTS: A total of 16 reports (26
patients, 2 from the ISCVT and 24 from the systematic review of the literature)
were included. No randomized clinical trial was found. Seven patients presented
with isolated intracranial hypertension syndrome (26.9%), 17 with encephalopathy
(65.4%) and 2 were comatose (7.7%). The superior sagittal sinus was the one most
often affected (n = 21; 80.8%), and there was thrombosis of the deep cerebral
venous system in 5 patients (19.2%). Urokinase was the thrombolytic agent most
frequently administered (n = 19; 73.1%), whereas streptokinase and recombinant
tissue plasminogen activator were used in 2 cases each (7.7%). Intracranial
hemorrhages occurred in 3 cases (11.5%). Extracranial hemorrhages occurred in 5
cases (19.2%), and overall there were 3 cases of serious bleeding (11.5%),
including 2 deaths (7.7%). Partial or complete recanalization was verified in
most patients (n = 16; 61.5%). The survival rate was 92.3% (24/26 patients). At
the last available follow-up, 22/25 patients regained independency (mRS scores 0
2; 88%), 2/25 died (mRS score 6; 8%) and 1/25 was severely dependent (mRS scores
3-5; 4%). CONCLUSIONS: In all, 88% of the CVT patients treated with systemic
thrombolysis regained their independency, but 2 deaths associated with
intracranial hemorrhage occurred. The mortality rate and disability at the last
available follow-up were similar to those found in 2 previous systematic reviews
concerning the use of thrombolytics in CVT. Due to the small sample size and lack
of controls, the efficacy of systemic thrombolysis in acute CVT cannot be
assessed from the published information. Concerning safety, a nonnegligible
proportion of bleedings was reported.
PMID- 24356182
TI - Fracture during intravenous bisphosphonate treatment in a child with osteogenesis
imperfecta: an argument for a more frequent, low-dose treatment regimen.
AB - BACKGROUND/AIMS: Intravenous bisphosphonate therapy is the mainstay of medical
treatment in osteogenesis imperfecta (OI) and has been shown to increase bone
mass, decrease bone pain, improve mobility, and reduce the incidence of
fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on
long bone radiographs following cyclical intravenous therapy. These areas create
stress risers within the bone that may act as foci for subsequent fractures as
exemplified in this clinical case. METHODS: An 8-year-old girl with OI sustained
a distal radial fracture following 3 years of treatment with 6-monthly
intravenous zoledronate. Her diagnosis, response to treatment, and subsequent
fracture at a sclerotic metaphyseal line is described. RESULTS: Peripheral
quantitative computer tomography was used to characterise the presence of
multiple stress risers at the distal forearm. Trabecular bone mineral density
fluctuated from 34 to 126% compared to neighbouring 2-mm regions. CONCLUSION:
There remain many unanswered questions about optimal bisphosphonate treatment
regimens in children with OI. The formation of stress risers following
intravenous bisphosphonate treatment raises the hypothesis that a more frequent
and low-dose bisphosphonate regimen would provide more uniform dosing of bone in
the growing child and reduce the likelihood of fractures compared to current
treatment practices.
PMID- 24356183
TI - The effect of montelukast and antiadhesion barrier solution on the capsule
formation after insertion of silicone implants in a white rat model.
AB - BACKGROUND AND PURPOSES: Capsular contracture is one of the most severe
complications that can occur in breast surgery following silicone implant
insertion. The purpose of this study was to investigate the effect of montelukast
and antiadhesion barrier solution (AABS) on reducing capsular formation and their
possible synergism. MATERIALS AND METHODS: This study was approved by the Animal
Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with
the Kyungpook National University - Institutional Animal Care and Use Committee,
Animal Ethics Committee. The experiments in this study were conducted in vivo in
4 groups of 24 rats. Following silicone implant insertion, the pocket was
injected with different agents. Group I (control group) was given normal saline
injections into the pocket and fed with pure water. Group II was given injections
of AABS and fed with pure water. Group III was given injections of normal saline
and the medication montelukast during the experimental period. Group IV was given
injections of AABS and montelukast as postoperative medication. Peri-implant
capsules were excised after 8 weeks and were evaluated for transparency,
inflammatory cell content, capsule thickness, collagen pattern and TGF-beta
expression. RESULTS: The capsules in the experimental groups (i.e., groups II-IV)
were significantly more transparent than those in group I (controls; p < 0.05,
Student's t test). The mean capsule thickness of the experimental groups II (296
+/- 14.76 MUm), III (280 +/- 14.77 MUm) and IV (276 +/- 39.28 MUm) was smaller
than that of the control group I (361 +/- 35.43 MUm). Compared to the control
group, the histologic findings in the experimental groups suggested a decreased
inflammatory response occurring in the peri-implant capsules as they exhibited
minor vascularization and a reduced number of mast cells and macrophages. The
collagen patterns in the experimental groups were of a lower density than in the
control group with the former showing a loose, tidy collagen pattern. The amounts
of TGF-beta and collagen I were higher in the control group than in the
experimental groups. Group IV (the synergic effect group) had a more pronounced
effect on all the parameters examined than that in groups II and III with
separate drug administration. CONCLUSIONS: Montelukast and AABS reduced the
thickness, the inflammatory cell infiltrate and the myofibroblast content of the
peri-implant capsules around silicone implants in this white rat model. They
lowered the expression of the fibrotic mediator, TGF-beta, and inhibited the peri
implant capsular fibrosis. Therefore, montelukast and AABS are effective in the
reduction of silicone-induced peri-implant capsular formation.
PMID- 24356184
TI - Variable range of the RKKY interaction in edged graphene.
AB - The indirect exchange interaction is one of the key factors in determining the
overall alignment of magnetic impurities embedded in metallic host materials. In
this work we examine the range of this interaction in magnetically doped graphene
systems in the presence of armchair edges using a combination of analytical and
numerical Green function approaches. We consider both a semi-infinite sheet of
graphene with a single armchair edge, and also quasi-one-dimensional armchair
edged graphene nanoribbons (GNRs). While we find signals of the bulk decay rate
in semi-infinite graphene and signals of the expected one-dimensional decay rate
in GNRs, we also find an unusually rapid decay for certain instances in both,
which manifests itself whenever the impurities are located at sites which are a
multiple of three atoms from the edge. This decay behavior emerges from both the
analytic and numerical calculations, and the result for semi-infinite graphene
can be interpreted as an intermediate case between ribbon and bulk systems.
PMID- 24356185
TI - Live human nasal epithelial cells (hNECs) on chip for in vitro testing of gaseous
formaldehyde toxicity via airway delivery.
AB - Cell models based on human nasal epithelial stem/progenitor cells (hNESPCs) are
developed to obtain functional ciliated cells on modified Transwell inserts. The
live hNECs are integrated into microfluidic platforms to mimic the 3D features of
the human upper airway for in vitro testing of gaseous formaldehyde toxicity via
airway delivery.
PMID- 24356186
TI - Mineral-organic hybrid nanotubes as highly sensitive solid state optical chemical
sensors.
AB - Hybrid materials represent one of the strategies of materials science for
accomplishing complex functionalities hardly encompassed by single-component
systems. The critical step in this approach is the mixing and/or bonding between
the two different components, which must preserve the original characteristics of
the materials or give rise to new functionalities originating from a proper and
controlled interaction between the two components. Here, we demonstrate the use
of the ionic self-assembly approach for fabricating functional nanomaterials
comprising an inorganic matrix constituted by synthetic geomimetic chrysotile
nanotubes and an organic superficial layer of a free-base porphyrin. The
resulting hybrid nanomaterial can be processed as colloidal solution and as thin
solid film. In both phases, the hybrid shows a bright red fluorescence under UV
blue excitation at ca. 400 nm. This fluorescence exhibits decreasing intensity
with decreasing pH, as a result of the porphyrin J-type aggregation strongly
catalyzed by the mineral surface. Simultaneously, the aggregation induces a neat
color change from red to green, serving as a fast direct visual test of pH
variations. These results open the route for the utilization of bio-compatible
and inert mineral nanomaterials with strong adsorbing properties as efficient and
cost-effective solid state vectors for functional molecules.
PMID- 24356187
TI - [Study of cross reactivity between proton pump inhibitors].
AB - Although rare, anaphylactic reactions induced by PPIs have been reported. The
presence of cross-reactivity between different members of the group is not clear.
We analyzed all cases of allergic skin reactions to PPIs notified in regional
pharmacovigilance center of Sfax during a 12 years period and assessed the
possibility of cross-reactions between different molecules of this class. An
enquiry of pharmacovigilance was conducted for each case according to the French
imputation method. We called then, all patients who developed an allergic
reaction to a PPI with a plausible or credible imputation. A patch test to all
the molecules was carried out to study the possibility of cross-reactivity
between PPIs. Thirty-seven patients have developed skin disease, with a total of
1 172 cutaneous adverse effects (3%) notified in our regional pharmacovigilance
center. The skin disease most frequently observed was maculopapular rash (19
cases or 51%), followed by urticaria in 9 cases (24%). The omeprazole was the
most implicated in the genesis of these adverse events (in 31 cases: 83.78%).
Lansoprazole was administered to 5 patients having allergy to omeprazole with
good tolerance. Patch tests were realized for6 patients having allergy to
omeprazole. They were positive with omeprazole at 72 h in all cases and negative
with lansoprazole in 5 cases. In one third of cases, lansoprazole was a good
alternative at patients developing allergy to omeprazole, esomeprazole or
pantoprazole. In one case we have contraindicated all PPIs. In the other cases we
have preconized surveillance for the use of lansoprazole.
PMID- 24356188
TI - [Adverse effects of sulfasalazine: discussion of mechanism and role of
sulfonamide structure].
AB - Sulfasalazine is widely used in the treatment of chronic inflammatory bowel
disease (IBD) and certain rheumatic diseases. However, its use is associated with
a high rate of adverse effects (AEs) which can be cutaneous, hematological,
renal, hepatic, gastrointestinal or neurological. The aim of our study was to
collect all cases of AEs suspected to be associated with the use of sulfasalazine
in patients hospitalized in the department of Gastroenterology from the Hospital
Hedi Chaker of Sfax (Tunisia) for a period of 5 years and to search the
incriminated fraction (sulfonamide or salicylate). Our study population included
69 patients who received sulfasalazine for the treatment of IBD. We collected, in
23 patients (33%), 25 AEs suspected to be related to sulfasalazine. Cutaneous and
hematological reactions are the most common. The subsequent administration of
mesalazine was performed in 15 patients. It was well tolerated in 14 patients. So
we were suspecting probably the responsibility of sulfonamide fraction in these
cases. The mechanism of sulfasalazine induced AEs may be toxic or immunoallergic
with the possibility of a cross-reaction with the other antimicroacterial
sulfonamides.
PMID- 24356189
TI - Prevalence and attitude towards smoking in first, third and fifth-year pharmacy
students in Spain: PRECOTABAC study.
AB - AIM OF THIS STUDY: The aim of this study is to calculate smoking prevalence among
first, third and fifth-year pharmacy students in Spain, and to describe their
attitude towards giving up smoking. METHODS: Cross-sectional multi-center study
using an ad hoc self-administered questionnaire in first, third and fifth-year
pharmacy students at seven Spanish universities. Bivariate analysis with chi
square and Student's t-test, statistical significance p<0.05. RESULTS: Smoking
prevalence: 34.92%. The smokers smoke 31.04 (SD=43.182) cigarettes/week on
average. Pharmacy students have a positive attitude towards giving up smoking,
with differences between year groups (p=0.036). CONCLUSIONS: Four in ten pharmacy
students in Spain smoke every day by the time they finish their degree. Smoking
prevalence is lower in the first few years of the degree and increases over time.
Students also have a positive attitude towards giving up smoking, and are in
favor of measures that can be taken to try to stop people smoking.
PMID- 24356190
TI - [Opioid therapy for chronic noncancer pain: retrospective analysis of patients
hospitalized for withdrawal].
AB - OBJECTIVE: The prescription of opioids for the treatment of chronic non-cancer
pain (CNCP) is not recommended for all of them, and can expose the patients to a
benefit/risk ratio unfavorable. The objective of this study was to evaluate the
management of patients hospitalized at the centre for evaluation and treatment of
pain for opioid withdrawal, their outcome during hospitalization. METHOD: This is
a retrospective descriptive study. The medical record of each patient was
consulted to identify relevant data (demographics, treatments at the entrance and
discharge of hospitalization, comorbidities, rating scale of pain). RESULTS:
During the study period (3 years), 53 patients (64% of women), with a median age
of 52 years, were included. Pain was mainly back pain and neck pain (52%).
Morphine (43%) and fentanyl (42%) were the most frequently used opioids. At
admission, 62% of patients had a depressive state. At hospital discharge,
withdrawal was total in 18 patients (34%) and a total improvement of pain was
observed for 19% of them. CONCLUSION: In this study, 57% of patients received, at
admission to hospital, an opioid other than morphine in the treatment of CNCP.
The management of pain offered by the pain clinic led to a total or partial
opioid withdrawal in 94% of patients.
PMID- 24356191
TI - Sulfasalazine-induced aseptic meningitis with positive rechallenge: a case report
and review of the literature.
PMID- 24356193
TI - Distribution of MLH1 foci in horse male synaptonemal complex.
AB - Advances in molecular cytogenetics have provided the opportunity to study events
during prophase I of meiosis. Immunofluorescent localization of different meiotic
protein components were used to characterize the early stages of the first
meiotic division in horse spermatocytes. The frequency and distribution of
recombination events during prophase I were investigated using the mutL homolog 1
(MLH1) protein that is known to be associated with these events. The frequency
and distribution of MLH1 foci were investigated in pachytene nuclei of 6 fertile
stallions, and the average relative synaptonemal complex length was found to be
highly correlated with the average number of MLH1 foci. The frequency and
distribution of MLH1 foci were found to closely correspond to the frequency and
distribution of chiasmata on metaphase I chromosomes, and genetic length,
calculated from MLH1 foci data, for the whole genome was 2,505.5 cM.
PMID- 24356192
TI - Differential expression of degradome components in cutaneous squamous cell
carcinomas.
AB - Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse
spectrum of squamous cell carcinoma has made it difficult for early diagnosis,
particularly the aggressive tumors that are highly associated with mortality.
Therefore, molecular markers are needed as an adjunct to current staging methods
for diagnosing high-risk lesions, and stratifying those patients with aggressive
tumors. To identify such biomarkers, we have examined a comprehensive set of 200
histologically defined squamous cell carcinoma and normal skin samples by using a
combination of microarray, QRT-PCR and immunohistochemistry analyses. A
characteristic and distinguishable profile including matrix metalloproteinase
(MMP) as well as other degradome components was differentially expressed in
squamous cell carcinoma compared with normal skin samples. The expression levels
of some of these genes including matrix metallopeptidase 1 (MMP1), matrix
metallopeptidase 10 (MMP10), parathyroid hormone-like hormone (PTHLH), cyclin
dependent kinase inhibitor 2A (CDKN2A), A disintegrin and metalloproteinase with
thrombospondin motifs 1 (ADAMTS1), FBJ osteosarcoma oncogene (FOS), interleukin 6
(IL6) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were
significantly differentially expressed (P<=0.02) in squamous cell carcinoma
compared with normal skin. Furthermore, based on receiver operating
characteristic analyses, the mRNA and protein levels of MMP1 are significantly
higher in aggressive tumors compared with non-aggressive tumors. Given that MMPs
represent the most prominent family of proteinases associated with tumorigenesis,
we believe that they may have an important role in modulating the tumor
microenvironment of squamous cell carcinoma.
PMID- 24356194
TI - Drug therapy in stroke: from preclinical to clinical studies.
AB - BACKGROUND: Stroke is one of the major challenges to health and the reason for
increasing disability-adjusted life years. Despite tremendous progress in
preclinical studies, none of the treatment options has proven efficacious in
clinical studies. The basic aim of neuroprotection is to interfere with the
events of the ischemic cascade, halt the pathological processes and prevent the
death of vulnerable nerve cells in the ischemic penumbra. SUMMARY: This review
will provide a brief overview of the current understanding of stroke, including
the global epidemiology of stroke, its pathophysiology, the targeting of specific
pathways and the success and failure of preclinical as well as clinical studies,
and it will discuss the emerging targets for novel therapeutic strategies under
investigation. KEY MESSAGES: New advancing investigational drugs for the
prevention and treatment of stroke are on the way and may someday give hope to
neuroscientists and clinicians. A novel approach should adopt preclinical
testing, advance the understanding of the pathophysiology of stroke and make it
possible to translate it from bench to bedside. We should learn from the past
failures and move on with more enthusiasm.
PMID- 24356196
TI - The monocarboxylate transporter inhibitor alpha-cyano-4-hydroxycinnamic acid
disrupts rat lung branching.
AB - BACKGROUND/AIMS: The human embryo develops in a hypoxic environment. In this way,
cells have to rely on the glycolytic pathway for energy supply, leading to an
intracellular accumulation of monocarboxylates such as lactate and pyruvate.
These acids have an important role in cell metabolism and their rapid transport
across the plasma membrane is crucial for the maintenance of intracellular pH
homeostasis. This transport is mediated by a family of transporters, designated
by monocarboxylate transporters (MCTs), namely isoforms 1 and 4. MCT1/4
expression is regulated by the ancillary protein CD147.The general aim of this
study was to characterize the expression pattern of MCT1/4, CD147 and the glucose
transporter GLUT1 during human fetal lung development and elucidate the role of
MCTs in lung development. METHODS: The expression pattern of MCT1/4 and GLUT1 was
characterized by immunohistochemistry and fetal lung viability and branching were
evaluated by exposing rat fetal lung explants to CHC, an inhibitor of MCT
activity. RESULTS: Our findings show that all the biomarkers are differently
expressed during fetal lung development and that CHC appears to have an
inhibitory effect on lung branching and viability, in a dose dependent way.
CONCLUSION: We provide evidence for the role of MCTs in embryo lung development,
however to prove the dependence of MCT activity further studies are waranted.
PMID- 24356197
TI - The comprehensive anatomical spinal osteotomy classification.
AB - BACKGROUND: Global sagittal malalignment is significantly correlated with health
related quality-of-life scores in the setting of spinal deformity. In order to
address rigid deformity patterns, the use of spinal osteotomies has seen a
substantial increase. Unfortunately, variations of established techniques and
hybrid combinations of osteotomies have made comparisons of outcomes difficult.
OBJECTIVE: To propose a classification system of anatomically-based spinal
osteotomies and provide a common language among spine specialists. METHODS: The
proposed classification system is based on 6 anatomic grades of resection (1
through 6) corresponding to the extent of bone resection and increasing degree of
destabilizing potential. In addition, a surgical approach modifier is added
(posterior approach or combined anterior and posterior approaches). Reliability
of the classification system was evaluated by an analysis of 16 clinical cases,
rated 2 times by 8 different readers, and calculation of Fleiss kappa
coefficients. RESULTS: Intraobserver reliability was classified as "almost
perfect"; Fleiss kappa coefficient averaged 0.96 (range, 0.92-1.0) for resection
type and 0.90 (0.71-1.0) for the approach modifier. Results from the
interobserver reliability for the classification were 0.96 for resection type and
0.88 for the approach modifier. CONCLUSION: This proposed anatomically based
classification system provides a consistent description of the various
osteotomies performed in spinal deformity correction surgery. The reliability
study confirmed that the classification is simple and consistent. Further
development of its use will provide a common frame for osteotomy assessment and
permit comparative analysis of different treatments.
PMID- 24356199
TI - In reply.
PMID- 24356200
TI - Commentary: magnetic resonance imaging assessment of cerebral arteriovenous
malformation obliteration after stereotactic radiosurgery.
PMID- 24356203
TI - Fanconi anemia founder mutation in Macedonian patients.
AB - BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive disorder clinically
characterized by developmental abnormalities, progressive bone marrow failure
(BMF) and profound cancer predisposition. Approximately 65% of all affected
individuals have mutation in the FANCA (Fanconi anemia complementation group A)
gene. The mutation spectrum of the FANCA gene is highly heterogeneous. FA-A is
usually associated with private FANCA mutations in individual families. METHODS:
We describe 3 unrelated patients with FA with a similar clinical presentation:
BMF, renal anomalies and cafe-au-lait pigmentation without major skeletal
abnormality. The molecular analysis of the FANCA gene using the FA MLPA kit P031
A2/P032 FANCA, showed homozygous deletion of exon 3 in all 3 patients. Molecular
analysis of the flanking regions of exon 3 precisely defined unique deletion of
2,040 bp and duplication of C (1788_3828dupC). DISCUSSION/CONCLUSIONS: These are
the first 3 patients homozygous for deletion of FANCA exon 3 described to date.
Although not related, the patients originated from the same Gypsy-like ethnic
population. We conclude that c.190-256_283 + 1680del2040 dupC mutation in the
FANCA gene is a founder mutation in Macedonian FA patients of Gypsy-like ethnic
origin. Our finding has very strong implications for these patients in
formulating diagnostic and carrier-screening strategy for BMF and FA and to
enable comprehensive genetic counseling.
PMID- 24356204
TI - Rana grylio virus (RGV) envelope protein 2L: subcellular localization and
essential roles in virus infectivity revealed by conditional lethal mutant.
AB - Rana grylio virus (RGV) is a pathogenic iridovirus that has resulted in high
mortality in cultured frog. Here, an envelope protein gene, 2L, was identified
from RGV and its possible role in virus infection was investigated. Database
searches found that RGV 2L had homologues in all sequenced iridoviruses and is a
core gene of iridoviruses. Western blotting detection of purified RGV virions
confirmed that 2L protein was associated with virion membrane. Fluorescence
localization revealed that 2L protein co-localized with viral factories in RGV
infected cells. In co-transfected cells, 2L protein co-localized with two other
viral envelope proteins, 22R and 53R. However, 2L protein did not co-localize
with the major capsid protein of RGV in co-transfected cells. Meanwhile,
fluorescence observation showed that 2L protein co-localized with endoplasmic
reticulum, but did not co-localize with mitochondria and Golgi apparatus.
Moreover, a conditional lethal mutant virus containing the lac repressor/operator
system was constructed to investigate the role of RGV 2L in virus infection. The
ability to form plaques and the virus titres were strongly reduced when
expression of 2L was repressed. Therefore, the current data showed that 2L
protein is essential for virus infection. Our study is the first report, to our
knowledge, of co-localization between envelope proteins in iridovirus and
provides new insights into the understanding of envelope proteins in iridovirus.
PMID- 24356205
TI - Validity of self-reported blood pressure control in people with hypertension
attending a primary care center.
AB - OBJECTIVES: The aim of this study was to estimate the validity of self-reported
blood pressure control and medication use in people with hypertension, with and
without diabetes. METHODS: In a sample of 161 patients with hypertension in a
family health team in Ontario, we applied questions from the 2009 Survey on
Living with Chronic Disease in Canada Hypertension Component and compared
responses against objectively measured and chart-abstracted clinical indicators.
Objective blood pressure control was defined as a blood pressure of less than
130/80 mmHg and less than 140/90 mmHg for individuals with and without diabetes,
respectively. RESULTS: Self-reported blood pressure control showed reasonable
sensitivity (83+/-11 and 78+/-10%) but low specificity (30+/-19 and 58+/-21%) in
people with and those without diabetes, respectively. In the subgroup with
diabetes, specificity improved to 88+/-11% when blood pressure control was
defined on the basis of a 140/90 mmHg target. Self-reported and chart-abstracted
numbers of prescribed antihypertensive medications showed fair agreement
(kappa=0.7); 9 and 14% of patients overestimated and underestimated the number of
prescribed medications, respectively. CONCLUSION: Although most individuals with
controlled hypertension reported having controlled blood pressure, a large
proportion of individuals with uncontrolled hypertension also reported that their
blood pressure was controlled. This level of misclassification suggests that in a
family medicine clinic population and in health survey contexts, a self-reported
measure of blood pressure control may not be useful for assessing hypertension
control.
PMID- 24356206
TI - Left heart structures in human neonates with congenital diaphragmatic hernia and
the effect of fetal endoscopic tracheal occlusion.
AB - BACKGROUND: Small left heart structures are observed in fetuses with left-sided
congenital diaphragmatic hernia (CDH). Fetoscopic tracheal occlusion (FETO) in
mid-gestation promotes lung growth in fetuses with CDH, however cardiac effects
of FETO are poorly described. We studied the effects of FETO on cardiac structure
size at birth, hypothesizing that left heart structures would be larger in
neonates who had undergone fetal intervention. METHODS/RESULTS: We performed
retrospective measurements of atrioventricular and semilunar valve and pulmonary
artery diameters, ventricular lengths, left ventricular end-diastolic volume
indexed (LVEDVi) to body surface area. 35 patients were studied (9 FETO, 26
controls). All fetuses had liver herniation and a lung-to-head ratio <1 at fetal
presentation. At birth the intervention group had larger LVEDVi (16.8 vs. 12.76
ml/m(2), p < 0.05), LV length Z-score (-2.05 vs. -4, p < 0.01), LV:RV length
ratio (1.43 vs. 1.04, p < 0.05), LPA diameter Z-score (+1.71 vs. -1.04, p <
0.05), and better growth of aortic valve (-2.18 FETO, -3.3 controls, p < 0.01).
There was a trend toward higher LV output in the FETO group. CONCLUSIONS: Left
heart structures and LPA were larger postnatally in patients with CDH who
underwent FETO than in those who did not. Hemodynamic alterations are introduced
with tracheal occlusion that are associated with alterations in ventricular
loading and may influence growth.
PMID- 24356207
TI - Viscous fingering and dendritic growth of surface crystallized Sr2TiSi2O8
fresnoite.
AB - During the quenching of a melt with the composition 2SrO.TiO2.2.75SiO2, cubic
SrTiO3- and tetragonal Sr2TiSi2O8-crystals are formed at the surface. Subsequent
crystal growth leads to dendritic fresnoite structures which become increasingly
finer until the mechanism changes to viscous fingering during further cooling. In
the final stages of this initial growth step, the crystal orientations of these
dendrites systematically change. Due to a complete absence of bulk nucleation in
this system, crystal growth is resumed upon reheating to 970 degrees C and
fractal growth with the c-axis tilted by about 45 degrees from the main growth
direction is observed. The results are interpreted to confirm the link between
viscous fingering and dendritic growth in the case of a true crystallization
process.
PMID- 24356208
TI - Oral sex, semen displacement, and sexual arousal: testing the ejaculate
adjustment hypothesis.
AB - Male Indian Flying Foxes (Pteropus giganteus) that spend more time performing
oral sex on a female also spend more time copulating with her. In humans, men who
spend more time copulating with their regular partner also perform more "semen
displacing" copulatory behaviors (e.g., deeper, more vigorous penile thrusting).
We investigated whether men who spend more time performing oral sex on their
regular partner also spend more time copulating with her and perform more semen
displacing copulatory behaviors. We proposed and tested the ejaculate adjustment
hypothesis for men's copulatory behaviors: Men adjust their copulatory behaviors
to increase their sexual arousal and consequent ejaculate quality, thereby
increasing their chances of success in sperm competition. Two hundred and thirty
three men in a committed, heterosexual relationship responded to questions about
their copulatory behavior and sexual arousal during their most recent sexual
encounter with their long-term partner. The results indicated that men who spend
more time performing oral sex on their partner also spend more time copulating
with her, perform more semen-displacing copulatory behaviors, and report greater
sexual arousal. We discuss limitations to the current research and highlight the
heuristic value of sperm competition theory for understanding human sexual
behaviors.
PMID- 24356209
TI - Returning incidental findings from genetic research to children: views of parents
of children affected by rare diseases.
AB - PURPOSE: To explore parental perceptions and experiences regarding the return of
genomic incidental research findings in children with rare diseases. METHODS:
Parents of children affected by various rare diseases were invited to participate
in focus groups or individual telephone interviews in Montreal and Ottawa.
Fifteen participants were interviewed and transcriptions were analysed using
thematic analysis. RESULTS: Four emergent themes underscored parental enthusiasm
for receiving incidental findings concerning their child's health: (1) right to
information; (2) perceived benefits and risks; (3) communication practicalities:
who, when, and how; and (4) service needs to promote the communication of
incidental findings. Parents believed they should be made aware of all results
pertaining to their child's health status, and that they are responsible for
transmitting this information to their child, irrespective of disease severity.
Despite potential negative consequences, respondents generally perceived a
favourable risk-benefit ratio in receiving all incidental findings. CONCLUSIONS:
Understanding how parents assess the risks and benefits of returning incidental
findings is essential to genomic research applications in paediatric medicine.
The authors believe the study findings will contribute to establishing future
best practices, although further research is needed to evaluate the impact of
parental decisions on themselves and their child.
PMID- 24356210
TI - New-onset dyspnea and right heart failure.
PMID- 24356211
TI - Electrical stimulation in treatment of pharyngolaryngeal dysfunctions.
AB - OBJECTIVE: Neuromuscular electrical stimulation (NMES) has been proposed in the
treatment of laryngopharyngeal dysfunctions (dysphonia, dyspnoea, dysphagia) for
more than 40 years. Several studies have investigated possible therapeutic
effects. Some researchers described favourable results, whereas others did not
find relevant benefits. This article aims to review available studies to give an
overview regarding the current state of knowledge. METHODS: We conducted a
selective literature search using PubMed. RESULTS: In total, 356 papers were
identified: 6 case reports, 11 reviews, 43 prospective clinical trials and 3
retrospective trials were found. CONCLUSION: Due to different stimulation
protocols, electrode positioning and various underlying pathological conditions,
summarizing the present studies appears to be difficult. However, there is
evidence that NMES is a valuable adjunct in patients with dysphagia and in
patients with vocal fold paresis. Nevertheless, more empirical data is needed to
fully understand the benefits provided by NMES. Further research suggestions are
put forward.
PMID- 24356212
TI - Excited states using the simplified Tamm-Dancoff-Approach for range-separated
hybrid density functionals: development and application.
AB - The recently introduced sTDA methodology [S. Grimme, J. Chem. Phys., 2013, 138,
244104] to compute excitation spectra of huge molecular systems is extended to
range-separated hybrid (RSH) density functionals. The three empirical parameters
of the method which describe a screened two-electron interaction are obtained for
some common RSH functionals (omegaB97 family, CAM-B3LYP, LC-BLYP) from a fit to
theoretical SCS-CC2 reference vertical excitation energies for a set of small to
medium-sized chromophores. The method is cross-validated on a set of inter- and
intramolecular charge transfer states and a set composed of typical valence
transitions. Overall small deviations from reference data of only about 0.2-0.4
eV are found with best performance for CAM-B3LYP and omegaB97X-D3. To demonstrate
versatility and robustness of the new methodology, applications (the UV/Vis
spectrum of the pyridine polymer and the ECD spectrum of (P)-[11]helicene) and
frequently used charge transfer examples are discussed. In one case, 11 000+
excited electronic states of a system containing 330 atoms were calculated. We
show that the asymptotically correct sTDA-RSH combination yields results often
superior to those based on global hybrids and that it opens up new possibilities
for the computation of excited states in materials science and bio-molecular
systems.
PMID- 24356213
TI - MD simulation of organics adsorption from aqueous solution in carbon slit-like
pores. Foundations of the pore blocking effect.
AB - The results of systematic studies of organics adsorption from aqueous solutions
(at the neutral pH level) in a system of slit-like carbon pores having different
sizes and oxygen groups located at the pore mouth are reported. Using molecular
dynamics simulations (GROMACS package) the properties of adsorbent-adsorbate
(benzene, phenol or paracetamol) as well as adsorbent-water systems are
discussed. After the introduction of surface oxygen functionalities, adsorption
of organic compounds decreases (in accordance with experimental data) and this is
caused by the accumulation of water molecules at pore entrances. The pore
blocking effect decreases with the diameter of slits and practically vanishes for
widths larger than approx. 0.68 nm. We observed the increase in phenol adsorption
with the rise in temperature. Moreover, adsorbed molecules occupy the external
surface of the slit pores (the entrances) in the case of oxidized adsorbents.
Among the studied molecules benzene, phenol and paracetamol prefer an almost flat
orientation and with the rise in the pore width the number of molecules oriented
in parallel decreases. The decrease or increase in temperature (with respect to
298 K) leads to insignificant changes of angular orientation of adsorbed
molecules.
PMID- 24356216
TI - Advances in the use of acidic potassium permanganate as a chemiluminescence
reagent: a review.
AB - We review the analytical applications of acidic potassium permanganate
chemiluminescence published since our previous comprehensive review in mid-2007
to early 2013. This includes a critical evaluation of evidence for the emitting
species, the influence of additives such as polyphosphates, formaldehyde,
sulfite, thiosulfate, lanthanide complexes and nanoparticles, the development of
a generalized reaction mechanism, and the use of this chemistry in
pharmaceutical, clinical, forensic, food science, agricultural and environmental
applications.
PMID- 24356215
TI - MALDI-target integrated platform for affinity-captured protein digestion.
AB - To address immunocapture of proteins in large cohorts of clinical samples high
throughput sample processing is required. Here a method using the proteomic
sample platform, ISET (integrated selective enrichment target) that integrates
highly specific immunoaffinity capture of protein biomarker, digestion and sample
cleanup with a direct interface to mass spectrometry is presented. The robustness
of the on-ISET protein digestion protocol was validated by MALDI MS analysis of
model proteins, ranging from 40 fmol to 1 pmol per nanovial. On-ISET digestion
and MALDI MS/MS analysis of immunoaffinity captured disease-associated biomarker
PSA (prostate specific antigen) from human seminal plasma are presented.
PMID- 24356217
TI - A partial least squares and wavelet-transform hybrid model to analyze carbon
content in coal using laser-induced breakdown spectroscopy.
AB - A partial least squares (PLS) and wavelet transform hybrid model are proposed to
analyze the carbon content of coal by using laser-induced breakdown spectroscopy
(LIBS). The hybrid model is composed of two steps of wavelet analysis procedures,
which include environmental denoising and background noise reduction, to pretreat
the LIBS spectrum. The processed wavelet coefficients, which contain the discrete
line information of the spectra, were taken as inputs for the PLS model for
calibration and prediction of carbon element. A higher signal-to-noise ratio of
carbon line was obtained after environmental denoising, and the best
decomposition level was determined after background noise reduction. The hybrid
model resulted in a significant improvement over the conventional PLS method
under different ambient environments, which include air, argon, and helium. The
average relative error of carbon decreased from 2.74 to 1.67% under an ambient
helium environment, which indicated a significantly improved accuracy in the
measurement of carbon in coal. The best results obtained under an ambient helium
environment could be partly attributed to the smallest interference by noise
after wavelet denoising. A similar improvement was observed in ambient air and
argon environments, thereby proving the applicability of the hybrid model under
different experimental conditions.
PMID- 24356218
TI - A strategy that iteratively retains informative variables for selecting optimal
variable subset in multivariate calibration.
AB - Nowadays, with a high dimensionality of dataset, it faces a great challenge in
the creation of effective methods which can select an optimal variables subset.
In this study, a strategy that considers the possible interaction effect among
variables through random combinations was proposed, called iteratively retaining
informative variables (IRIV). Moreover, the variables are classified into four
categories as strongly informative, weakly informative, uninformative and
interfering variables. On this basis, IRIV retains both the strongly and weakly
informative variables in every iterative round until no uninformative and
interfering variables exist. Three datasets were employed to investigate the
performance of IRIV coupled with partial least squares (PLS). The results show
that IRIV is a good alternative for variable selection strategy when compared
with three outstanding and frequently used variable selection methods such as
genetic algorithm-PLS, Monte Carlo uninformative variable elimination by PLS (MC
UVE-PLS) and competitive adaptive reweighted sampling (CARS). The MATLAB source
code of IRIV can be freely downloaded for academy research at the website:
http://code.google.com/p/multivariate-calibration/downloads/list.
PMID- 24356219
TI - Ultrasensitive electrochemical immunosensors for multiplexed determination using
mesoporous platinum nanoparticles as nonenzymatic labels.
AB - An ultrasensitive multiplexed immunoassay method was developed at a disposable
immunosensor array using mesoporous platinum nanoparticles (M-Pt NPs) as
nonenzymatic labels. M-Pt NPs were prepared by ultrasonic method and employed to
label the secondary antibody (Ab2) for signal amplification. The immunosensor
array was constructed by covalently immobilizing capture antibody (Ab1) on
graphene modified screen printed carbon electrodes (SPECs). After the sandwich
type immunoreactions, the M-Pt-Ab2 was bound to immunosensor surface to catalyze
the electro-reduction of H2O2 reaction, which produced detectable signals for
readout of analytes. Using breast cancer related panel of tumor markers (CA125,
CA153 and CEA) as model analytes, this method showed wide linear ranges of over 4
orders of magnitude with the detection limits of 0.002 U mL(-1), 0.001 U mL(-1)
and 7.0 pg mL(-1) for CA125, CA153 and CEA, respectively. The disposable
immunosensor array possessed excellent clinical value in cancer screening as well
as convenient point of care diagnostics.
PMID- 24356220
TI - Development of solid-phase microextraction to study dissolved organic matter-
polycyclic aromatic hydrocarbon interactions in aquatic environment.
AB - Solid-phase microextraction coupled with gas chromatography and mass spectrometry
(SPME-GC-MS) was developed for the study of interactions between polycyclic
aromatic hydrocarbons (PAHs) and dissolved organic matter (DOM). After the
determination of the best conditions of extraction, the tool was applied to
spiked water to calculate the dissolved organic carbon water distribution
coefficient (K(DOC)) in presence of different mixtures of PAHs and Aldrich humic
acid. The use of deuterated naphthalene as internal standard for freely dissolved
PAH quantification was shown to provide more accuracy than regular external
calibration. For the first time, K(DOC) values of 18 PAHs were calculated using
data from SPME-GC-MS and fluorescence quenching; they were in agreement with the
results of previous studies. Competition between PAHs, deuterated PAHs and DOM
was demonstrated, pointing out the non-linearity of PAH-DOM interactions and the
stronger interactions of light molecular weight PAHs (higher K(DOC) values) in
absence of high molecular weight PAHs.
PMID- 24356221
TI - Effervescence assisted dispersive liquid-liquid microextraction with extractant
removal by magnetic nanoparticles.
AB - In this article, effervescence assisted dispersive liquid-liquid microextraction
with extractant removal by magnetic nanoparticles is presented for the first
time. The extraction technique makes use of a mixture of 1-octanol and bare Fe3O4
magnetic nanoparticles (MNPs) in acetic acid. This mixture is injected into the
sample, which is previously fortified with carbonate, and as a consequence of the
effervescence reaction, CO2 bubbles are generated making possible the easy
dispersion of the extraction solvent. In addition, the MNPs facilitates the
recovery of the 1-octanol after the extraction thanks to the interaction between
hydroxyl groups present at the surface of the MNPs and the alcohol functional
group of the solvent. The extraction mode has been optimized and characterized
using the determination of six herbicides in water samples as model analytical
problem. The enrichment factors obtained for the analytes were in the range 21
185. These values permit the determination of the target analytes at the low
microgram per liter range with good precision (relative standard deviations lower
than 11.7%) using gas chromatography (GC) coupled to mass spectrometry (MS) as
analytical technique.
PMID- 24356222
TI - The use of coenzyme Q0 as a template in the development of a molecularly
imprinted polymer for the selective recognition of coenzyme Q10.
AB - In this work, a novel molecularly imprinted polymer (MIP) for use as a solid
phase extraction sorbent was developed for the determination of coenzyme Q10
(CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial
oxidative phosphorylation and a powerful antioxidant agent found in low
concentrations in biological samples. This fact and its high hydrophobicity make
the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised
using coenzyme Q0 as the template, methacrylic acid as the functional monomer,
acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker
and benzoyl peroxide as the initiator. Various parameters affecting the polymer
preparation and extraction efficiency were evaluated. Morphological
characterisation of the MIP and its proper comparison with C18 as a sorbent in
solid phase extraction were performed. The optimal conditions for the molecularly
imprinted solid phase extraction (MISPE) consisted of 400 MUL of sample mixed
with 30 mg of MIP and 600 MUL of water to reach the optimum solution loading. The
loading was followed by a washing step consisting of 1 mL of a 1-propanol
solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After
clean-up, the CoQ10 in the samples was analysed by high performance liquid
chromatography. The extraction recoveries were higher than 73.7% with good
precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5
MUg g(-1), respectively, and a linear range between 7.5 and 150 MUg g(-1) of
tissue was achieved. The new MISPE procedure provided a successful clean-up for
the determination of CoQ10 in a complex matrix.
PMID- 24356223
TI - Evaluation of matrix effect in isotope dilution mass spectrometry based on
quantitative analysis of chloramphenicol residues in milk powder.
AB - In the present study, we developed a comprehensive strategy to evaluate matrix
effect (ME) and its impact on the results of isotope dilution mass spectrometry
(IDMS) in analysis of chloramphenicol (CAP) residues in milk powder. Stable
isotope-labeled internal standards do not always compensate ME, which brings the
variation of the ratio (the peak area of analyte/the peak area of isotope). In
our investigation, impact factors of this variation were studied in the
extraction solution of milk powder using three mass spectrometers coupled with
different ion source designs, and deuterium-labeled chloramphenicol (D5-CAP) was
used as the internal standard. ME from mobile phases, sample solvents, pre
treatment methods, sample origins and instruments was evaluated, and its impact
on the results of IDMS was assessed using the IDMS correction factor (theta). Our
data showed that the impact of ME of mobile phase on the correction factor was
significantly greater than that of sample solvent. Significant ion suppression
and enhancement effects were observed in different pre-treated sample solutions.
The IDMS correction factor in liquid-liquid extraction (LLE) and molecular
imprinted polymer (MIP) extract with different instruments was greater or less
1.0, and the IDMS correction factor in hydrophilic lipophilic balance (HLB) and
mix-mode cation exchange (MCX) extract with different instruments was all close
to 1.0. To the instrument coupled with different ion source design, the impact of
ME on IDMS quantitative results was significantly different, exhibiting a large
deviation of 11.5%. Taken together, appropriate chromatographic conditions, pre
treatment methods and instruments were crucial to overcome ME and obtain reliable
results, when IDMS methods were used in the quantitative analysis of trace target
in complex sample matrix.
PMID- 24356224
TI - Deciphering the structure of isomeric oligosaccharides in a complex mixture by
tandem mass spectrometry: photon activation with vacuum ultra-violet brings
unique information and enables definitive structure assignment.
AB - Carbohydrates have a wide variety of structures whose complexity and
heterogeneity challenge the field of analytical chemistry. Tandem mass
spectrometry, with its remarkable sensitivity and high information content,
provides key advantages to addressing the structural elucidation of
polysaccharides. Yet, classical fragmentation by collision-activated dissociation
(CAD) in many cases fails to reach a comprehensive structural determination,
especially when isomers have to be differentiated. In this work, for the first
time, vacuum ultra-violet (VUV) synchrotron radiation is used as the activation
process in tandem mass spectrometry of large oligosaccharides. Compared to low
energy CAD (LE-CAD), photon activated dissociation brought more straightforward
and valuable structural information. The outstanding feature was that complete
series of informative ions were produced, with only minor neutral losses.
Moreover, systematic fragmentation rules could be drawn thus facilitating the
definitive assignments of fragment identities. As a result, most of the
structures present in a complex mixture of oligogalacturonans could be
comprehensively resolved, including many isomers differing in the position of
methyl groups along the galacturonic acid backbone.
PMID- 24356225
TI - Lipid characterization of embryo zones by silica plate laser desorption
ionization mass spectrometry imaging (SP-LDI-MSI).
AB - Lipid pathways play important biological roles in mammalian embryology, directing
early developmental pathways to differentiation. Phospholipids and triglycerides,
among others, are the main composing lipids of zona pellucida in several embryo
species. Lipid analysis in embryos by mass spectrometry usually requires sample
preparation and/or matrix application. This novel approach using silica plate
laser desorption/ionization mass spectrometry imaging (SP-LDI-MSI) allows direct
single-cell imaging and embryo region discrimination with no matrix coating. Its
application is herein described for two- and eight-cell embryos. Lipid biomarkers
for blastomere and intact zona pellucida are reported and corroborated by both
fragmentation reactions (MS/MS) and images. Results obtained in this work are
understood to be of great use for further developments on in vitro bovine
fertilization. Since much of the processes can be monitored by characteristic
biomarkers, it is now possible to precisely identify cell division errors during
early embryo stages, as well as evaluate pre-implantation conditions.
PMID- 24356226
TI - Multi-analyte quantification in bioprocesses by Fourier-transform-infrared
spectroscopy by partial least squares regression and multivariate curve
resolution.
AB - This paper presents the quantification of Penicillin V and phenoxyacetic acid, a
precursor, inline during Pencillium chrysogenum fermentations by FTIR
spectroscopy and partial least squares (PLS) regression and multivariate curve
resolution - alternating least squares (MCR-ALS). First, the applicability of an
attenuated total reflection FTIR fiber optic probe was assessed offline by
measuring standards of the analytes of interest and investigating matrix effects
of the fermentation broth. Then measurements were performed inline during four
fed-batch fermentations with online HPLC for the determination of Penicillin V
and phenoxyacetic acid as reference analysis. PLS and MCR-ALS models were built
using these data and validated by comparison of single analyte spectra with the
selectivity ratio of the PLS models and the extracted spectral traces of the MCR
ALS models, respectively. The achieved root mean square errors of cross
validation for the PLS regressions were 0.22 g L(-1) for Penicillin V and 0.32 g
L(-1) for phenoxyacetic acid and the root mean square errors of prediction for
MCR-ALS were 0.23 g L(-1) for Penicillin V and 0.15 g L(-1) for phenoxyacetic
acid. A general work-flow for building and assessing chemometric regression
models for the quantification of multiple analytes in bioprocesses by FTIR
spectroscopy is given.
PMID- 24356227
TI - A rapid fluorescence based method for the quantitative analysis of cell culture
media photo-degradation.
AB - Cell culture media are very complex chemical mixtures that are one of the most
important aspects in biopharmaceutical manufacturing. The complex composition of
many media leads to materials that are inherently unstable and of particular
concern, is media photo-damage which can adversely affect cell culture
performance. This can be significant particularly with small scale transparent
bioreactors and media containers are used for process development or research.
Chromatographic and/or mass spectrometry based analyses are often time-consuming
and expensive for routine high-throughput media analysis particularly during
scale up or development processes. Fluorescence excitation-emission matrix (EEM)
spectroscopy combined with multi-way chemometrics is a robust methodology
applicable for the analysis of raw materials, media, and bioprocess broths. Here
we demonstrate how EEM spectroscopy was used for the rapid, quantitative analysis
of media degradation caused by ambient visible light exposure. The primary
degradation pathways involve riboflavin (leading to the formation of lumichrome,
LmC) which also causes photo-sensitised degradation of tryptophan, which was
validated using high pressure liquid chromatography (HPLC) measurements. The use
of PARallel FACtor analysis (PARAFAC), multivariate curve resolution (MCR), and N
way partial least squares (NPLS) enabled the rapid and easy monitoring of the
compositional changes in tryptophan (Trp), tyrosine (Tyr), and riboflavin (Rf)
concentration caused by ambient light exposure. Excellent agreement between HPLC
and EEM methods was found for the change in Trp, Rf, and LmC concentrations.
PMID- 24356228
TI - A non-aggregation colorimetric assay for thrombin based on catalytic properties
of silver nanoparticles.
AB - In this paper, we developed a simple and rapid colorimetric assay for protein
detection based on the reduction of dye molecules catalyzed by silver
nanoparticles (AgNPs). Aptamer-modified magnetic particles and aptamer
functionalized AgNPs were employed as capture and detection probes, respectively.
Introduction of thrombin as target protein could form a sandwich-type complex
involving catalytically active AgNPs, whose catalytic activity was monitored on
the catalytic reduction of rhodamine B (RhB) by sodium borohydride (NaBH4). The
amount of immobilized AgNPs on the complex increased along with the increase of
the thrombin concentration, thus the detection of thrombin was achieved via
recording the decrease in absorbance corresponding to RhB. This method has
adopted several advantages from the key factors involved, i.e., the sandwich
binding of affinity aptamers contributed to the increased specificity; magnetic
particles could result in rapid capture and separation processes; the conjugation
of AgNPs would lead to a clear visual detection. It allows for the detection
limit of thrombin down to picomolar level by the naked eye, with remarkable
selectivity over other proteins. Moreover, it is possible to apply this method to
the other targets with two binding sites as well.
PMID- 24356229
TI - A new fluorescent turn-on chemodosimeter for mercury ions in solution and its
application in cells and organisms.
AB - Using the Hg(2+)-induced desulfurization reaction of thiosemicarbazide
derivative, we designed and synthesized a novel "turn on" coumarin-based
fluorescent probe L with a simple structure for detecting mercury ion (II).
Spectroscopy revealed that the probe responds selectively to mercury ions over
other metal ions with marked fluorescence enhancement. Detection of Hg(2+) was
effective at pH 7.0-9.5, with high selectivity and significant effect in HeLa
cells, human umbilical vein endothelial cells and Escherichia coli, but no
cytotoxicity. This probe could be an ideal and practical Hg(2+) probe with
important biological significance.
PMID- 24356231
TI - How to select equivalent and complimentary reversed phase liquid chromatography
columns from column characterization databases.
AB - Three RP-LC column characterization protocols [Tanaka et al. (1989), Snyder et
al. (PQRI, 2002), and NIST SRM 870 (2000)] were evaluated using both Euclidian
distance and Principal Components Analysis to evaluate effectiveness at
identifying equivalent columns. These databases utilize specific chromatographic
properties such as hydrophobicity, hydrogen bonding, shape/steric selectivity,
and ion exchange capacity of stationary phases. The chromatographic parameters of
each test were shown to be uncorrelated. Despite this, the three protocols were
equally successful in identifying similar and/or dissimilar stationary phases.
The veracity of the results has been supported by some real life pharmaceutical
separations. The use of Principal Component Analysis to identify
similar/dissimilar phases appears to have some limitations in terms of loss of
information. In contrast, the use of Euclidian distances is a much more
convenient and reliable approach. The use of auto scaled data is favoured over
the use of weighted factors as the former data transformation is less affected by
the addition or removal of columns from the database. The use of these free
databases and their corresponding software tools shown to be valid for
identifying similar columns with equivalent chromatographic selectivity and
retention as a "backup column". In addition, dissimilar columns with
complimentary chromatographic selectivity can be identified for method
development screening strategies.
PMID- 24356230
TI - Metabolic profiling of yeast culture using gas chromatography coupled with
orthogonal acceleration accurate mass time-of-flight mass spectrometry:
application to biomarker discovery.
AB - Yeast and yeast cultures are frequently used as additives in diets of dairy cows.
Beneficial effects from the inclusion of yeast culture in diets for dairy mammals
have been reported, and the aim of this study was to develop a comprehensive
analytical method for the accurate mass identification of the 'global'
metabolites in order to differentiate a variety of yeasts at varying growth
stages (Diamond V XP, Yea-Sacc and Levucell). Microwave-assisted derivatization
for metabolic profiling is demonstrated through the analysis of differing yeast
samples developed for cattle feed, which include a wide range of metabolites of
interest covering a large range of compound classes. Accurate identification of
the components was undertaken using GC-oa-ToFMS (gas chromatography-orthogonal
acceleration-time-of-flight mass spectrometry), followed by principal component
analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS
DA) for data reduction and biomarker discovery. Semi-quantification (fold changes
in relative peak areas) was reported for metabolites identified as possible
discriminative biomarkers (p-value <0.05, fold change >2), including D-ribose
(four fold decrease), myo-inositol (five fold increase), L-phenylalanine (three
fold increase), glucopyranoside (two fold increase), fructose (three fold
increase) and threitol (three fold increase) respectively.
PMID- 24356232
TI - Contactless conductivity detection for screening myrosinase substrates by
capillary electrophoresis.
AB - Myrosinase is a unique enzyme that catalyzes the hydrolysis of glucosinolates
(GLS) to isothiocyanate (ITC), glucose and sulfate. Isothiocyanates display a
diversified very interesting biological activity. In this study, capillary
electrophoresis (CE) was used for the first time for evaluating myrosinase
kinetics (maximum velocity Vmax and Michaelis-Menten constant Km) and to assess
the affinity of a variety of substrates toward this enzyme. The pre-capillary
approach was chosen since it is very simple to conduct. For this, the enzymatic
reaction was performed in a micro-vial. The reaction mixture volume was of only
100 MUL and the incubation lasted only 5 min at 37+/-1 degrees C. Short-end
injection of few tens of nanoliters (~25 nL) of the reaction mixture was
performed which decreased analysis time without using any electroosmotic
modifier. The sulfate produced was detected and quantified with a contactless
capacitively coupled conductivity detector (C(4)D) allowing the evaluation of
myrosinase kinetics. This study shows, that capillary electrophoresis with
contactless conductivity detection can be very useful for monitoring myrosinase
activity. Comparing to the conventional spectrophotometric method (1982), the CE
method developed here is simple, automated, economic, rapid (incubation for few
minutes) and robust. Results compared very well with those reported in literature
using the conventional method. Moreover, the affinity of a variety of natural and
synthetic glucosinolates toward this enzyme has been assessed for the first time.
PMID- 24356233
TI - An analytical method for determination of fullerenes and functionalized
fullerenes in soils with high performance liquid chromatography and UV detection.
AB - Fullerenes are carbon-based nanomaterials expected to play a major role in
emerging nanotechnology and produced at an increasing rate for industrial and
household applications. In the last decade a number of novel compounds (i.e.
fullerene derivatives) is being introduced into the market and specific
analytical methods are needed for analytical purposes as well as environmental
and safety issues. In the present work eight fullerenes (C60 and C70) and
functionalized fullerenes (C60 and C70 exohedral-derivatives) were selected and a
novel liquid chromatographic method was developed for their analysis with UV
absorption as a method of detection. The resulting HPLC-UV method is the first
one suitable for the analysis of all eight compounds. This method was applied for
the analysis of fullerenes added to clayish, sandy and loess top-soils at
concentrations of 20, 10 and 5 MUg kg(-1) and extracted with a combination of
sonication and shaking extraction. The analytical method limits of detection
(LoD) and limits of quantification (LoQ) were in the range of 6-10 MUg L(-1) and
15-24 MUg L(-1) respectively for the analytical solutions. The extraction from
soil was highly reproducible with recoveries ranging from 47+/-5 to 71+/-4%
whereas LoD and LoQ for all soils tested were of 3 MUg kg(-1) and 10 MUg kg(-1)
respectively. No significant difference in the extraction performance was
observed depending of the different soil matrices and between the different
concentrations. The developed method can be applied for the study of the fate and
toxicity of fullerenes in complex matrices at relatively low concentrations and
in principle it will be suitable for the analysis of other types of
functionalized fullerenes that were not included in this work.
PMID- 24356234
TI - Perinatal mortality and advanced maternal age.
AB - OBJECTIVE: To investigate the impact of advanced maternal age on the rate of
perinatal mortality. DESIGN: Retrospective cohort study including all 56,517
singleton hospital deliveries between 1999 and 2008. METHODS: Data were analyzed
according to maternal age at delivery in 3 groups of women, 25-34 years, 35-39
years and >= 40 years, using the youngest as the reference group. RESULTS: Odds
ratios (ORs) for antenatal deaths were 0.98 (CI: 0.67-1.43) and 2.57 (CI: 1.57
4.22) for age groups 35-39 years and >= 40 years, respectively. Significant
differences in neonatal mortality rates between the age groups were not found.
Significant amendable risk factors were attendance of <4 health care visits (OR =
15.55, CI: 9.47-25.51 in age group 35-39 years; OR = 16.38, CI: 9.78-27.43 in the
age group >= 40 years) and obesity (OR = 1.85, CI: 1.27-2.70 in age group 35-39
years; OR = 1.83, CI: 1.22-2.74 in the age group >= 40 years). In the
multivariate regression analysis, the adjusted ORs for perinatal mortality were
1.03 (95% CI: 0.77-1.39) and 1.66 (95% CI: 1.03-2.66) for age groups 35-39 and >=
40, respectively. CONCLUSIONS: Women older than 40 years carry an increased risk
for stillbirth. Important amendable risk factors are obesity and poor antenatal
care.
PMID- 24356235
TI - Understanding RPE lipofuscin.
PMID- 24356236
TI - Postural changes of 24-hour intraocular pressure in normal-tension glaucoma.
PMID- 24356237
TI - Author response: Postural changes of 24-hour intraocular pressure in normal
tension glaucoma.
PMID- 24356238
TI - Development of a quantitative approach using surface-enhanced Raman chemical
imaging: first step for the determination of an impurity in a pharmaceutical
model.
AB - This publication reports, for the first time, the development of a quantitative
approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical
model presented as tablets based on paracetamol, which is the most sold drug
around the world, was used to develop this approach. 4-Aminophenol is the main
impurity of paracetamol and is actively researched in pharmaceutical formulations
because of its toxicity. As its concentration is generally very low (<0.1%, w/w),
conventional Raman chemical imaging cannot be used. In this context, a SER-CI
method was developed to quantify 4-aminophenol assessing a limit of
quantification below its limit of specification of 1000 ppm. Citrate-reduced
silver nanoparticles were used as SERS substrate and these nanoparticles were
functionalized using 1-butanethiol. Different ways to cover the tablets surface
by butanethiol-functionalized silver nanoparticles were tested and a homogeneity
study of the silver nanoparticles covering was realized. This homogeneity study
was performed in order to choose the best way to cover the surface of tablets by
silver colloid. Afterwards, the optimization of the SER-CI approach was necessary
and different spectral intensity normalizations were tested. Finally, a
quantitative approach using SER-CI was developed enabling to quantify 4
aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative
approach was tested on two different series of tablets using different batches of
silver nanoparticles.
PMID- 24356239
TI - NOD2 deficiency protects against cardiac remodeling after myocardial infarction
in mice.
AB - BACKGROUND/AIMS: Although the pathogenesis of myocardial infarction (MI) is
multifactorial, activation of innate immune system to induce inflammation has
emerged as a key pathophysiological process in MI. NOD2, one member of the NOD
like receptor (NLR) family, plays an important role in the innate immune
response. This study was to examine the role of NOD2 during MI. METHODS: MI was
induced by permanent ligation of the left coronary artery in wild type and NOD2(
/-) mice and cardiac fibroblasts were isolated. RESULTS: NOD2 expression was
significantly increased in myocardium in post-MI mice. NOD2 deficiency improved
cardiac dysfunction and remodeling after MI as evidenced by echocardiographic
analysis, reduced the levels of cytokines, inflammatory cell infiltration and
matrix metalloproteinase-9 (MMP-9) activity. In vitro, we further found that NOD2
activation induced the activation of MAPK signaling pathways, production of
proinflammatory mediators and MMP-9 activity in cardiac fibroblasts. CONCLUSIONS:
Our studies demonstrate that NOD2 is a critical component of a signal
transduction pathway that links cardiac injury by exacerbation of inflammation
and MMP-9 activity. Pharmacological targeting of NOD2-mediated signaling pathways
may provide a novel approach to treatment of cardiovascular diseases.
PMID- 24356240
TI - Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a
Porcine Model of Meconium Aspiration Syndrome.
AB - BACKGROUND: Meconium displaces surfactant from the alveolar surface and inhibits
its function. The development of active synthetic surfactants is complicated,
especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A
synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed
to act similarly to the natural surfactant poractant alfa. OBJECTIVE: To test the
resistance to meconium inactivation of CHF5633 compared to poractant alfa.
Secondary outcome measurements were respiratory and inflammatory parameters.
METHODS: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to
receive either poractant alfa or CHF5633. After anesthesia, surgery and final
stabilization, meconium was instilled endotracheally followed by surfactant.
Bronchial lavage fluid was obtained before intervention and every second hour.
Respiratory parameters were registered and blood samples drawn before
intervention and every hour. RESULTS: Surfactant was inactivated in both groups 6
h after meconium instillation, but CHF5633 was more resistant than poractant alfa
in terms of lipid peroxidation. Respiratory parameters were similar in both
groups. Inflammatory and hemostatic parameters differed between groups,
suggesting that the surfactants may play different roles in the meconium-induced
inflammatory process. Due to the differential effects and complex pattern
observed, the data do not indicate that one of the surfactants was superior with
respect to inflammatory and hemostatic responses. CONCLUSION: This study
indicates that CHF5633 is as efficient as poractant alfa in experimental meconium
aspiration syndrome.
PMID- 24356241
TI - Autologous collagen-induced chondrogenesis using fibrin and atelocollagen
mixture.
AB - For articular cartilage defect treatment, many treatment modalities have been
developed. We evaluate the cartilage repair potential of an atelocollagen and
fibrin mixture transplanted to cartilage defects. A circular, articular cartilage
defect 4 mm in diameter was made in the trochlear region in each of 20 New
Zealand white rabbits. The 10 rabbits in the control group were kept without
treatment and the 10 rabbits in the experimental group underwent injection of
atelocollagen mixed with fibrin. At week 12 following surgery the cartilage was
observed and histologically compared in both groups. The surface of the newly
generated cartilage was very smooth and even, and we also noted that the entire
area was completely regenerated in the experimental group. The control group
showed incomplete and irregular cartilage formation in the defect. Regarding the
histological scoring, comparison of the two groups differed significantly (p <
0.001). Injection of a mixture of atelocollagen and fibrin used to treat
articular cartilage defects of the knee appears to be an effective method for
cartilage regeneration.
PMID- 24356242
TI - Nondeletional alpha-thalassemia (alpha2- IVS-1-116, A>G HBA2): an alpha2 gene
point mutation detected in an African-American female for the first time.
PMID- 24356243
TI - Cannabis finds its way into treatment of Crohn's disease.
AB - In ancient medicine, cannabis has been widely used to cure disturbances and
inflammation of the bowel. A recent clinical study now shows that the medicinal
plant Cannabis sativa has lived up to expectations and proved to be highly
efficient in cases of inflammatory bowel diseases. In a prospective placebo
controlled study, it has been shown what has been largely anticipated from
anecdotal reports, i.e. that cannabis produces significant clinical benefits in
patients with Crohn's disease. The mechanisms involved are not yet clear but most
likely include peripheral actions on cannabinoid receptors 1 and 2, and may also
include central actions.
PMID- 24356244
TI - Hong Kong domestic health spending: financial years 1989/90 to 2010/11.
AB - This report presents the latest estimates of Hong Kong domestic health spending
for financial years 1989/90 to 2010/11, cross-stratified and categorised by
financing source, provider, and function.Total expenditure on health (TEH) was
HK$93 433 million in financial year 2010/11, which represents an increase of
HK$5364 million or 6.1% over the preceding year. As a result of a gradual
recovery from the financial tsunami in 2008, gross domestic product (GDP) grew
faster relative to TEH leading to a drop in TEH as a percentage of GDP from 5.2%
in 2009/10 to 5.1% in 2010/11.During the period 1989/90 to 2010/11, TEH per
capita (at constant 2011 prices)grew at an average annual rate of 4.8%, which was
faster than the average annual growth rate of per capita GDP by 1.8 percentage
points.Compared to 2009/10, in 2010/11 public and private expenditure on health
increased by 3.7% and 8.5% and reached HK$45 491 million and HK$47 943 million,
respectively. Consequently, the public share of TEH dropped slightly from 49.8%
to 48.7% over the year. Regarding private spending, the most important source was
out-of-pocket payments by households (35.0% of TEH),followed by employer-provided
group medical benefits (7.4%), and private insurance (7.2%). It is worth noting
that private insurance will likely overtake employer benefits as the second
largest private payer if the insurance market continues to expand at the current
rate.Of the HK$93 433 million TEH in 2010/11, HK$88 987 million (95.2%) was
current expenditure and HK$4446 million (4.8%) was for capital expenses (ie
investment in medical facilities). Analysed by health care function, services for
curative care accounted for the largest share of TEH (65.8%), which was made up
of ambulatory services (34.0%), in-patient curative care (27.0%), day patient
hospital services (4.2%), and home care (0.5%). Notwithstanding its small
share,the total spending for day patient hospital services shows an increasing
trend over the period 1989/90 to 2010/11, which is likely due to shift of policy
directives from in-patient to day patient care, and the increasing demand for
dialysis and cataract surgery in an ageing population.Hospitals accounted for an
increasing share of TEH, from 28.2% in 1989/90 to 46.8% in 2002/03 and then
dropped slightly to 43% to 44%during the period 2005/06 to 2010/11, which was
primarily driven by reduced expenditure by the Hospital Authority. As a result of
several epidemics (e g avian flu, SARS, swine flu) and expansion of the private
health insurance market in the last two decades, spending on the provision and
administration of public health programmes, and general health administration and
insurance accounted for increasing, though less significant, shares of TEH over
that period.Without taking into account capital expenses (ie investment in
medical facilities), public current expenditure on health amounted to HK$42 264
million(47.5% of total current expenditure) in 2010/11. The remaining HK$46 723
million was from private sources. Public current expenditure was mostly incurred
at hospitals (74.7%), whereas private current expenditure was mostly incurred at
providers of ambulatory health care (51.0%). Although both public and private
spending were mostly expended on personal health care services and goods (91.4%of
total current spending), the distributional patterns among functional categories
differed. Public expenditure was targeted at in-patient care (47.6%) and
substantially less on out-patient care (27.5%). In comparison, private spending
was mostly concentrated on out-patient care (43.2%),whereas in-patient care
(24.5%) and medical goods outside the patient care setting (19.9%) accounted for
most of the remaining share. Compared to the Organisation for Economic
Cooperation and Development countries, Hong Kong has devoted a relatively low
percentage of GDP to healthcare in the last decade. As a share of TEH, public
funding(either general government revenue or social security funds) was also
lower than in most economies with comparable economic development and public
revenue collection base.
PMID- 24356245
TI - Genetics of growth.
PMID- 24356246
TI - Editorial: gloriously autumnal.
PMID- 24356247
TI - White grain mycetoma caused by Scedosporium apiospermum in North India: a case
report.
AB - Mycetoma is chronic granulomatous infection of skin and subcutaneous tissue
caused by both bacteria and fungi. We report a case of mycetoma caused by
Scedosporium apiospermum in the right foot of a 45-year-old farmer in north
India. The patient had a history of trauma in the sole of the right foot followed
by discharge of white granules along with proximal progression. Scedosporium
apiospermum was identified based on colony characteristics and microscopic
features on slide culture. Mycetoma is a progressive disease. Foot is commonly
affected in persons who walk barefoot, especially in south India. Untreated
mycetoma progress and involve the underlying fasciae and tissues along with bones
often resulting in loss of limb. By prompt and reliable diagnosis with
corresponding antimicrobial administration, we can prevent further progression
and limb disability.
PMID- 24356248
TI - Elephantasis nostras verrucosa and psoriasis: only a coincidence?
PMID- 24356249
TI - Lower extremity amputation: a complete series from a tertiary hospital.
PMID- 24356250
TI - Comprehensive overview of definitions for optical coherence tomography-based
plaque and stent analyses.
AB - Optical coherence tomography (OCT) is the current state-of-the-art intracoronary
imaging modality that allows visualization of detailed morphological
characteristics of both atherosclerotic plaque and stent. So far, three expert
review documents have been released for standardization of OCT image analysis. In
the real world, a variety of definitions are being used by different groups and
by different core laboratories to analyze OCT findings because of different
clinical/procedural contexts in which OCT research has been carried out. This
comprehensive overview is aimed to summarize different applicable definitions
used by different research groups in plaque and stent analysis using OCT. In
addition, it presents readers with a panoramic view to select the best definition
of OCT measurement for one's own study purpose. We divided this review article
into two parts: Part I - Plaque analysis, and Part II - Stent analysis. The
plaque analysis section summarizes the definitions of plaque composition,
rupture, erosion, protruding calcific nodules, macrophages, microvessels, and
cholesterol crystal. The stent analysis section includes the classification of
stent struts, features of neointimal hyperplasia, and other stent-related
findings such as tissue protrusion, thrombus, intrastent, and stent edge
dissections. In each case of controversy, an explanation for the specific context
is provided.
PMID- 24356251
TI - ALK is a MYCN target gene and regulates cell migration and invasion in
neuroblastoma.
AB - Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is
mutated or amplified in NBLs. To obtain a better understanding of the molecular
events associated with ALK in the pathogenesis of NBL, it is necessary to clarify
how ALK gene contributes to NBL progression. In the present study, we found that
ALK expression was significantly high in NBL clinical samples with amplified MYCN
(n = 126, P < 0.01) and in developing tumors of MYCN-transgenic mice. Indeed,
promoter analysis revealed that ALK is a direct transcriptional target of MYCN.
Overexpression and knockdown of ALK demonstrated its function in cell
proliferation, migration and invasion. Moreover, treatment with an ALK inhibitor,
TAE-684, efficiently suppressed such biological effects in MYCN amplified cells
and tumor growth of the xenograft in mice. Our present findings explore the
fundamental understanding of ALK in order to develop novel therapeutic tools by
targeting ALK for aggressive NBL treatment.
PMID- 24356253
TI - Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when
administered twice daily according to FDA weight bands.
AB - BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are
approved by the United States Food and Drug Administration (FDA) and European
Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is
based on body weight bands or body surface area under FDA approval and only body
surface area by the EMA. This can lead to a different recommended dose. In
addition, weight band-based dosing has not been formally studied in the target
population. We evaluated the pharmacokinetics (PK) of LPV/r in children,
administered twice daily according to the FDA weight bands, using pediatric
tablets. METHODS: Fifty-three HIV-infected children were included in the PK
substudy of the Paediatric European Network for the Treatment of AIDS 18 trial
(KONCERT). In this study, children were randomized to receive LPV/r twice or once
daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and
20 children in the 15-25 kg, >= 25-35 kg and >35 kg weight band, respectively,
while children took the tablets twice daily. Rich sampling was performed, and PK
parameters were calculated by noncompartmental analysis. Given the high
percentage of Asian children, it was also tested whether there was a difference
in PK parameters between Asian and non-Asian children. RESULTS: For the total
group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h * mg/L, 12.0 mg/L
and 4.9 mg/L, respectively. There were no significant differences in LPV PK
parameters between the weight bands. In addition, weight was not found to be
associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters.
CONCLUSIONS: FDA weight band-based dosing recommendations provide adequate
exposure to LPV when using LPV/r pediatric tablets.
PMID- 24356254
TI - Treatment trends and outcomes in US hospital stays of children with empyema.
AB - BACKGROUND: Recently published practice guidelines continue to reflect
uncertainty about the comparative effectiveness of various treatments for empyema
in children. We describe treatment trends and outcomes in pediatric empyema using
the most current nationally representative data. METHODS: Using survey methods
and Kids' Inpatient Databases from 1997 to 2009, we evaluated hospital stays in
children 0-18 years of age. We used 2009 data to compare transfer-out rates and
lengths of stay across various types of treatment, after adjusting for patient
and hospital factors. RESULTS: From 1997 to 2009, empyema discharges steadily
increased from 3.1 to 6.0 per 100,000 children (P < 0.001 for trend) and also
were increasingly likely (P < 0.01) to be coded for: (1) at least 1 pleural
drainage procedure (76.4-83.2%), (2) multiple drainage procedures (36.0-41.6%)
and (3) home health care (8.7-15.0%). By 2009, video-assisted thoracoscopic
surgery was more commonly coded than chest tube drainage and was associated with
a lower transfer-out rate (0.6% vs. 10.1%, adjusted P < 0.001) but no reduction
in mean length of stay [11.2 vs. 13.4 days, adjusted incidence rate ratio 0.95
(95% confidence interval: 0.88-1.04)] for children neither admitted nor
discharged by transfer. CONCLUSIONS: US hospital stays for empyema in children
not only continued to increase through 2009 but were also characterized by more
intense procedural management. Outcomes results in this population-based study
are consistent with practice guidelines and recommendations that recently
endorsed chest tube drainage as an acceptable first treatment option for most
children with empyema.
PMID- 24356252
TI - Parkinson's disease gene therapy: success by design meets failure by efficacy.
AB - Over the past decade, nine gene therapy clinical trials for Parkinson's disease
(PD) have been initiated and completed. Starting with considerable optimism at
the initiation of each trial, none of the programs has yet borne sufficiently
robust clinical efficacy or found a clear path toward regulatory approval.
Despite the immediately disappointing nature of the efficacy outcomes in these
trials, the clinical data garnered from the individual studies nonetheless
represent tangible and significant progress for the gene therapy field.
Collectively, the clinical trials demonstrate that we have overcome the major
safety hurdles previously suppressing central nervous system (CNS) gene therapy,
for none produced any evidence of untoward risk or harm after administration of
various vector-delivery systems. More importantly, these studies also
demonstrated controlled, highly persistent generation of biologically active
proteins targeted to structures deep in the human brain. Therefore, a renewed,
focused emphasis must be placed on advancing clinical efficacy by improving
clinical trial design, patient selection and outcome measures, developing more
predictive animal models to support clinical testing, carefully performing
retrospective analyses, and most importantly moving forward-beyond our past
limits.
PMID- 24356255
TI - Afebrile very young infants with urinary tract infection and the risk for
bacteremia.
AB - BACKGROUND: Some authors have assessed the utility of considering various risk
factors in predicting bacteremia in young infants with urinary tract infection
(UTI) in studies that included only febrile patients. Our aims were to determine
whether fever was a predictor for bacteremia and to identify other associated
risk factors. METHODS: A retrospective study was conducted that included infants
29 to 90 days of age with UTI attended in the Pediatric Emergency Department from
September 2006 through May 2013. UTI was defined as growth of >= 50,000 colony
forming units/mL of a single pathogen from a catheterized specimen in association
with an abnormal urinalysis. Patients without a blood culture were excluded.
Univariate testing was used to identify clinical and laboratory factors
associated with bacteremia. Receiver operating characteristic curves were
constructed for the laboratory markers associated with bacteremia. RESULTS: We
analyzed 350 patients; 77 (22%) were afebrile. Ten had bacteremia (2.9%, 95%
confidence interval: 1.6%-5.2%). No other adverse events were identified. No
differences were found in bacteremia rates between febrile and afebrile patients
(2.9% vs. 2.6%; P = 1.0). Risk factors detected for bacteremia were classified as
not well-appearing (25.0% vs. 2.1%; P = 0.003) and a procalcitonin value >= 0.7
ng/mL (6.4% vs. 0.5%; P = 0.001). These low-risk criteria yielded a sensitivity
of 88.9% for detecting bacteremia with a negative predictive value of 99.5%.
CONCLUSIONS: Afebrile young infants with UTI should not be classified a priori as
low risk for bacteremia. Well-appearing young infants with UTI and procalcitonin
value <0.7 ng/mL were at very low risk for bacteremia; outpatient management with
an appropriate follow-up could be considered.
PMID- 24356258
TI - Impact of obturation of palatal fistulae on speech quality and aerodynamic
parameters in patients with cleft palates.
AB - OBJECTIVES: The aim of this prospective study was to measure nasal and oral
airflow during speech, before and after obturation. PATIENTS AND METHODS:
Included were children aged 3-18 years with nonsyndromic clefts and palatal
fistulae. The corpus used was: syllable /pi/; a sentence containing stop
consonants and a nasal phoneme; and the description of a picture of a scene.
Analysis criteria were: percentage of nasality; value of average flow for the
explosion; perceived nasality and intelligibility; and tolerance of the proposed
device. RESULTS: Only 5 children were included due to the observation of an
increase in the percentage of nasality after obturation. The value of average
flow for the explosion increased in all patients. A decrease in perceived
nasality was noted in all but 1 patient. An improvement in intelligibility was
observed in 3 out of the 5 children. The tolerance of the device was good.
CONCLUSION: While the small number of patients studied does not permit firm
conclusions concerning the efficiency of the obturation, the method described, as
well as the introduction of 'speed of explosion' of stop consonants, offer new
perspectives to prospectively study obturator effects on speech.
PMID- 24356256
TI - Motavizumab treatment of infants hospitalized with respiratory syncytial virus
infection does not decrease viral load or severity of illness.
AB - BACKGROUND: This study was conducted to determine whether treatment with
motavizumab, an anti-respiratory syncytial virus (RSV) monoclonal antibody, would
decrease viral load and improve clinical outcomes in previously healthy term
infants hospitalized with RSV lower respiratory tract infection. METHODS: Infants
hospitalized with lower respiratory tract infection and a positive RSV test
performed locally were randomized to receive 1 intravenous dose of motavizumab
(30 or 100 mg/kg) or placebo. Nasal wash samples were tested by real-time reverse
transcriptase polymerase chain reaction at a central laboratory to determine
viral load. Clinical data were collected during RSV hospitalization and at 12
month follow up. RESULTS: Of 118 infants, 112 were confirmed RSV positive by real
time reverse transcriptase polymerase chain reaction. In each study group, median
(range) RSV load (log10 copies/mL) decreased at a similar rate from baseline to
study day 7 [motavizumab 30 mg/kg: 8.35 (2.5-9.5) to 5.03 (2.5-6.8); motavizumab
100 mg/kg: 8.22 (5.5-9.7) to 4.25 (2.5-8.0); placebo: 8.02 (6.7-9.8) to 5.17 (2.5
7.3)]. Median (range) duration of hospitalization was 3.05 (0.8-16.0), 2.99 (1.0
25.0) and 2.88 (0.8-11.7) days for the motavizumab 30 mg/kg, motavizumab 100
mg/kg and placebo groups, respectively. Six (8%) motavizumab and 0 placebo
recipients were admitted to the intensive care unit and 4 required mechanical
ventilation. The incidence of wheezing episodes during the 12-month follow up was
comparable for all 3 groups. CONCLUSIONS: Motavizumab had no appreciable effect
on RSV viral load measured in the upper respiratory tract of children
hospitalized for RSV lower respiratory tract infection. No differences were
observed for duration of hospitalization, severity of illness measures or
wheezing episodes during 12-month follow up in children treated with motavizumab
or placebo.
PMID- 24356259
TI - Sexual hormones modulate compensatory renal growth and function.
AB - The role played by sexual hormones and vasoactive substances in the compensatory
renal growth (CRG) that follows uninephrectomy (uNx) is still controversial.
Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx,
performed at 90 days age, were studied at age 150 days. Daily urine volume,
electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards,
glomerular filtration rate and blood pressure were measured, the kidneys weighed
and DNA, protein and RNA studied to determine nuclei content and cell size. When
the remnant kidney weight at age 150 days was compared with the weight of the
kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%)
while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized,
female and ovariectomized rats, respectively. The small CRG observed in the uNx
female rats was accompanied by the lowest glomerular filtration value, 0.56 +/-
0.02 ml/ min/g kwt compared, with the other uNx groups, p < 0.05. Cell size
(protein or RNA/DNA) was similar for all the groups except for uNx
orchidectomized rats. In this group the cytoplasmatic protein or RNA content was
lower than in the other groups while DNA (nuclei content) was similar. Some
degree of hyperplasia was determined by DNA content in the uNx groups. Male
sexual hormones positively influenced CRG and its absence modulated cell size.
Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein
kinin system may not be involved in CRG.
PMID- 24356260
TI - [Insulin and diabetes control in Argentina].
AB - As in the rest of the world, there is a significant gap between scientific
knowledge regarding diabetes mellitus and the daily practice outcome, in
Argentina. Inadequate diabetes control combined with associated cardiovascular
risk factors are responsible for an elevated morbid-mortality incidence and the
consequent raise in the socioeconomic burden. Some of the factors leading to this
situation are the late diagnosis of the disease, the clinical "inertia"
(reluctance to prescribe insulin) and the poor education given to the health care
team as well as the persons with diabetes. The implementation of a national
diabetologic education program targeting health care providers, the persons with
diabetes and their families, could contribute to optimize the appropriate insulin
prescription, and consequently improve their life quality, while reducing the
disease socioeconomic burden. In order to optimize the education program's
strategy outcome, insulinization cabinets should be incorporated, the
participation of all health systems (public health, social security and private
health insurance companies), the media, health sciences, schools and the
pharmaceutical industry are needed.
PMID- 24356261
TI - [Analysis of factors associated with chronic hypercapnia in patients with
myotonic dystrophy].
AB - Myotonic dystrophy (DM) is the most common dystrophy in adults. Several factors
may explain the chronic CO2 retention. The selection of patients, different
clinical stages and evaluation forms may explain the differing results obtained.
Our objectives were to characterize respiratory function and to evaluate factors
associated with chronic retention of CO2 in DM. We included 27 consecutive
ambulatory and stable patients who were allocated into normocapnic and
hypercapnic groups (PaCO2 >= 43 mmHg). Forced vital capacity (FVC), maximum
static pressure, voluntary apnea time, Epworth scale and arterial blood gases
were measured. The CO2 chemosensitivity was assessed using CO2 rebreathing (Read
method). The slope DeltaP0.1/DeltaPCO2 expressed the CO2 chemosensitivity. A
59.3% (16/27) presented hypercapnia. FVC and respiratory muscle strength were
normal or showed mild to moderate decrease. No significant differences in these
variables were found in both groups. Inadequate response to CO2 (slope
DeltaP0.1/DeltaPCO2 low (< 0.1 cm H2O/mmHg) or flat) was associated with
hypercapnia (p < 0.005). Chronic retention of CO2 represented 11.56 times higher
risk of inadequate response to CO2. The group with low-flat slope
DeltaP0.1/DeltaPCO2 showed higher PaCO2 (p = 0.0017) and more prolonged voluntary
apnea time (p = 0.002). We conclude that in our patients with DM, chronic CO2
retention was associated with the presence of abnormalities of the central
control of breathing. Our results allow explaining previous reports describing
the striking frequency of postoperative respiratory failure and difficulties in
the process of weaning from mechanical ventilation.
PMID- 24356262
TI - [Cytarabine and skin reactions in acute myeloid leukemia].
AB - Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia
(AML). It has many adverse effects as: myelosuppression, toxic reactions
involving central nervous system, liver, gastrointestinal tract, eyes or skin.
Dermatologic toxicity is often described as rare; nevertheless there are
differences in the reported frequency. We performed a retrospective study
including all AML treated with chemotherapy that involved cytarabine between 1st
July of 2006 and 1st July of 2012; 46 patients were included with a median age of
55 years. The overall incidence of skin reactions was 39% (n = 18). Sex, age,
history of atopy, history of drug reactions, or dose of cytarabine used, were not
associated with them. Skin reactions were observed from 2 to 8 days after
treatment started. Considering injury degree: 27.8% had grade 1, 38.9% grade 2
and 33.3% grade 3. We did not find any injury grade 4 or death associated with
skin toxicity. As for the type of injury: 55.6% presented macules, 22.2% papules
and 22.2% erythema. Lesions distribution was diffuse in 52% of patients, acral in
39.3%, and at flexural level in 8.7%. Adverse cutaneous reactions secondary to
the administration of cytarabine are frequent in our service and include some
cases with severe involvement. Although these reactions usually resolve
spontaneously, they determine an increased risk of infection and a compromise of
the patient quality of life.
PMID- 24356263
TI - Telementoring systems in the operating room: a new approach in medical training.
AB - This paper discusses the challenges and innovations related to the use of
telementoring systems in the operating room. Most of the systems presented
leverage on three types of interaction channels: audio, visual and physical. The
audio channel enables the mentor to verbally instruct the trainee, and allows the
trainee to ask questions. The visual channel is used to deliver annotations,
alerts and other messages graphically to the trainee during the surgery. These
visual representations are often displayed through a telestrator. The physical
channel has been used in laparoscopic procedures by partially controlling the
laparoscope through force-feedback. While in face to face instruction, the mentor
produces gestures to convey certain aspects of the surgical instruction, there is
not equivalent of this form of physical interaction between the mentor and
trainee in open surgical procedures in telementoring systems. Even that the trend
is to perform more minimally invasive surgery (MIS), trauma surgeries are still
necessary, where initial resuscitation and stabilization of the patient in a
timely manner is crucial. This paper presents a preliminary study conducted at
the Indiana University Medical School and Purdue University, where initial
lexicons of surgical instructive gestures (SIGs) were determined through
systematic observation when mentor and trainee operate together. The paper
concludes with potential ways to convey gestural information through surgical
robots.
PMID- 24356264
TI - [Multiple cerebral aneurysms in a patient with AIDS].
PMID- 24356265
TI - [Interhemispheric subdural hematoma].
PMID- 24356266
TI - [Science and art: tribute to Francois Jacob].
PMID- 24356267
TI - [The broad phenotypic spectrum of SCA-3: hereditary spastic paraplegia].
AB - Machado-Joseph disease (MJD) is the most frequent dominantly inherited
spinocerebellar ataxia. A marked phenotypic variability is a characteristic of
this disorder that could involve non-cerebellar presentations. Based on several
case reports describing pyramidal dysfunction as the main symptom at onset, a
clinical form resembling hereditary spastic paraplegia has been proposed. We
report here two further cases of MJD patients whose initial clinical presentation
suggested hereditary spastic paraplegia, and a summary of the main findings of
previously similar published reports. Our findings lent support to the proposal
of a MJD subtype distinguished by a marked pyramidal dysfunction at onset,
simulating a clinical picture of hereditary spastic paraplegia.
PMID- 24356268
TI - [Primary intra-osseous carcinoma].
AB - Primary intra-osseous carcinoma (PIOC) is a rare tumor, defined as squamous cell
carcinoma that develops in the jaw bones, having no initial connection to
adjacent skin or mucosa. It is locally aggressive, with metastases to regional
lymph nodes, (28% of cases) and lung (5% of cases) at the time of diagnosis. Its
origin may be di novo or from other odontogenic tumors. The maxillary bones have
epithelial tissues; therefore this neoplasm is located exclusively on this site,
predominantly in the jaw. PIOC diagnostic criteria are strict and include:
squamous cell carcinoma histopathology, lack of commitment and sinus mucosa,
ruling out the possibility of metastasis from a distant site with a thorough
clinical study and complementary methods. The treatment is, whenever possible,
oncologic resection, additional radio and / or chemotherapy. Reconstructive
surgery with graft and / or prostheses for aesthetic and functional are also
required. We report the case of a 72 years old man who consulted for sore jaw
three months after molar extraction. Curettage biopsy was performed and then
resected mandible with lymphadenectomy. Histopathological examination showed a
poorly differentiated squamous cell carcinoma, infiltrating jawbone with
morphological findings linking him to residual odontogenic cyst and metastatic
lymph nodes in 15 of 48 isolates. Postoperative radiotherapy was performed, he
died at 30 months of diagnosis by progressive deterioration.
PMID- 24356269
TI - [Foodborne dermatosis after traveling: gnathostomiasis].
AB - We describe a case of a 32-year-old man, resident in Buenos Aires, with
dermatologic manifestations compatible with gnathostomiasis. The patient had
traveled to Colombia in the month prior to the onset of symptoms. There, he
repeatedly ate ceviche (raw fish marinated in lemon juice). He presented with an
erythematous migratory panniculitis accompanied by eosinophilia. He underwent
skin biopsy of a lesion and pathological diagnosis was "eosinophilic
panniculitis". The triad of migratory panniculitis, eosinophilia and consume of
raw fish during the trip to Colombia was suggestive of gnathostomiasis.
Ivermectin treatment started out with good initial response but subsequent
relapse. We performed a new treatment with the same drug with good results and no
relapses during three years of follow up. The dermatological disease is common
upon return from a trip, and is the third leading cause of morbidity in
travelers. It is very important to recognize cutaneous manifestations of disease
as many of them are potentially serious and may compromise the patient's life if
not promptly diagnosed and treated.
PMID- 24356270
TI - [The endocrine heart and inflammation].
AB - The endocrine heart produces the polypeptide hormones Atrial Natriuretic Factor
(ANF or ANP) and Brain Natriuretic Peptide (BNP). Through the peripheral actions
of these hormones the heart contributes to the regulation of the cardiac preload
and afterload. More recently, new functions for these hormones have been
described including the modulation of the immune response. Plasma levels of BNP
but not those of ANF, increase following an acute rejection episode of a cardiac
allotransplant but return to levels pre-rejection with successful treatment. This
observation constitutes the first observation leading to characterizing the
interactions of BNP with the immune response. Several other pathologies with an
inflammatory component are now known to be associated with an increase in the
production of BNP. Such an increase is due to an increase in the transcriptional
activity of the BNP gene induced by cytokines and related substances. In vitro
investigations have shown that an increase in BNP directly modulates
immunological activity. Inflammation and hemodynamic changes co-exist in several
cardiovascular diseases and therefore it may be beneficial to measure circulating
levels of both ANF and BNP as biomarkers of changes in intravascular volume and
of changes in intravascular volume plus inflammation, respectively. Changes in
plasma ANF, that are relatively larger than those of BNP, might be an indication
of hemodynamic deterioration while important changes in circulating BNP could
indicate a worsening of the inflammatory process.
PMID- 24356271
TI - [Colorectal cancer screening with colonoscopy].
AB - Colorectal cancer is one of the leading causes of cancer death worldwide and also
in Argentina. In the past few years colorectal cancer screening has become more
popular and colonoscopy has been postulated as the gold standard. In this review
we analyzed the evidence supporting this method in contrast with its
complications and disadvantages.
PMID- 24356272
TI - [Amyotrophic lateral sclerosis: is the astrocyte the cell primarily involved?].
AB - So far, amyotrophic lateral sclerosis (ALS) is thought as due to a primary insult
of the motor neurons. None of its pathogenic processes proved to be the cause of
the illness, nor can be blamed environmental agents. Motor neurons die by
apoptosis, leaving the possibility that their death might be due to an unfriendly
environment, unable to sustain their health, rather than being directly targeted
themselves. These reasons justify an examination of the astrocytes, because they
have the most important role controlling the neurons' environment. It is known
that astrocytes are plastic, enslaving their functions to the requirements of the
neurons to which they are related. Each population of astrocytes is unique, and
if it were affected the consequences would reach the neurons that it normally
sustains. In regard to the motor neurons, this situation would lead to a
disturbed production and release of astrocytic neurotransmitters and
transporters, impairing nutritional and trophic support as well. For explaining
the spreading of muscle symptoms in ALS, correlated with the type of spreading
observed at the cortical and spinal motor neurons pools, the present hypotheses
suggests that the illness-causing process is spreading among astrocytes, through
their gap junctions, depriving the motor neurons of their support. Also it is
postulated that a normal astrocytic protein becomes misfolded and infectious,
inducing the misfolding of its wild type, travelling from one protoplasmatic
astrocyte to another and to the fibrous astrocytes encircling the pyramidal
pathway which joints the upper and lower motoneurones.
PMID- 24356273
TI - [A critical analysis of cortisol measurements: an update].
AB - Serum cortisol measurement is a very useful tool in the biochemical evaluation of
adrenocortical function. Since this hormone circulates in blood mainly linked to
binding globulins but is also partially free, it can be measured not only in the
blood but also in urine, saliva and other biological fluids and tissues. Basal
determinations as well as dynamic testing may be performed to evaluate the
circadian variations, to estimate the diurnal cortisol secretion and to analyze
its relations with other components of the hypothalamic-pituitary-adrenal axis.
Measurements of cortisol in blood, saliva and urine may reflect the cortisol
secretion at the time of sample collection or during a 24 h span. Recently, it
has been proposed the determination of cortisol in tissues such as hair and nails
like a means of evaluating the hormonal status during prolonged periods. The aim
of this paper is to update the methodology for measuring cortisol and its
usefulness for the clinical diagnosis of troubles of the hypothalamic-pituitary
adrenal axis.
PMID- 24356274
TI - [Human papillomavirus detection in cervical cancer prevention].
AB - Cervical cancer (CC), which is strongly associated to high-risk human
papillomavirus (hr-HPV) infection, continues being a significant health problem
in Latin America. The use of conventional cytology to detect precancerous
cervical lesions has had no major impact on reducing CC incidence and mortality
rates, which are still high in the region. New screening tools to detect
precancerous lesions became available, which provide great opportunities for CC
prevention, as do highly efficacious HPV vaccines able to prevent nearly all
lesions associated with HPV-16 and -18 when applied before viral exposure.
Currently, hr-HPV testing represents an invaluable component of clinical
guidelines for screening, management and treatment of CC and their precursor
lesions. Many testing strategies have been developed that can detect a broad
spectrum of hr-HPV types in a single assay; however, only a small subset of them
has documented clinical performance for any of the standard HPV testing
indications. HPV tests that have not been validated and lack proof of
reliability, reproducibility and accuracy should not be used in clinical
management. Once incorporated into the lab, it is essential to submit the whole
procedure of HPV testing to continuous and rigorous quality assurance to avoid
sub-optimal, potentially harmful practices. Recent progress and current status of
these methods are discussed in this article.
PMID- 24356275
TI - [Argentine scientific publications].
PMID- 24356276
TI - [The right to palliative care or "the day when death decided to return"].
PMID- 24356277
TI - [Groups C and G streptococcal pharyngitis].
PMID- 24356278
TI - [On the role of groups C and G streptococci in acute pharyngitis].
PMID- 24356279
TI - [Diarrhea and quadriparesis with dermatomyositis].
PMID- 24356280
TI - Significant enhancement in the thermoelectric performance of strained nanoporous
Si.
AB - Increasing demand for energy with fossil fuel supplies decreasing makes it an
urgent task to develop novel and cost-effective materials that can supply
environmentally benign and sustainable energy. To address this important issue,
in the present work we carry out a systematic study on the effect of external
strain on the room-temperature thermoelectric properties of Si containing
cylindrical pores in a periodic arrangement (nanoporous Si, or np-Si), based on
density functional theory and the Boltzmann transport equation. Within the
relaxation time approximation, it is demonstrated that the electrical
conductivity (sigma) and Seebeck coefficient (S) of np-Si remain unchanged from
the strain-free values under biaxial or shear strain. However, orthorhombic
strain increases sigma and S by as large as 68% and 110% compared to the
unstrained structure, respectively, which is found to originate from the broken
planar symmetry induced by the applied strain. Combined with the thermal
conductivity, the improvement in sigma and S of orthorhombically strained np-Si
can enhance the maximum value of the thermoelectric figure of merit to as high as
0.8, which makes strain engineering particularly attractive for high-performance
thermoelectrics.
PMID- 24356281
TI - Induction of apoptosis by the medium-chain length fatty acid lauric acid in colon
cancer cells due to induction of oxidative stress.
AB - BACKGROUND: Fatty acids are classified as short-chain (SCFA), medium-chain (MCFA)
or long-chain and hold promise as adjunctive chemotherapeutic agents for the
treatment of colorectal cancer. The antineoplastic potential of MCFA remains
underexplored; accordingly, we compared the MCFA lauric acid (C12:0) to the SCFA
butyrate (C4:0) in terms of their capacity to induce apoptosis, modify
glutathione (GSH) levels, generate reactive oxygen species (ROS), and modify
phases of the cell cycle in Caco-2 and IEC-6 intestinal cell lines. METHODS: Caco
2 and IEC-6 cells were treated with lauric acid, butyrate, or vehicle controls.
Apoptosis, ROS, and cell cycle analysis were determined by flow cytometry. GSH
availability was assessed by enzymology. RESULTS: Lauric acid induced apoptosis
in Caco-2 (p < 0.05) and IEC-6 cells (p < 0.05) compared to butyrate. In Caco-2
cells, lauric acid reduced GSH availability and generated ROS compared to
butyrate (p < 0.05). Lauric acid reduced Caco-2 and IEC-6 cells in G0/G1and
arrested cells in the S and G2/M phases. Lauric acid induced apoptosis in IEC-6
cells compared to butyrate (p < 0.05). Butyrate protected IEC-6 cells from ROS
induced damage, whereas lauric acid induced high levels of ROS compared to
butyrate. CONCLUSION: Compared to butyrate, lauric acid displayed preferential
antineoplastic properties, including induction of apoptosis in a CRC cell line.
PMID- 24356282
TI - Rituximab in previously treated primary immune thrombocytopenia patients:
evaluation of short- and long-term efficacy and safety.
AB - The anti-CD20 chimeric monoclonal antibody rituximab has been effectively used in
the treatment of patients with primary immune thrombocytopenia (pITP). We
retrospectively evaluated 19 patients affected by pITP resistant to 2 or more
lines of therapy who were treated with rituximab. Nine of the 19 patients showed
an initial response (47.4%). The sustained response rate was 31.6% (6/19). The
median follow-up of the patients was 53.2 months (range 9.2-92.9). Disease-free
survival at 48 months was 62.2%. Following rituximab treatment, a proportion of
patients (42%) recovered a normal B lymphocyte number. During the follow-up, no
opportunistic or severe infectious complications were observed. These data
confirm, over a long period of observation, the efficacy and safety of rituximab
treatment in the management of patients with resistant pITP.
PMID- 24356283
TI - Association of TSH concentrations and thyroid autoimmunity with IVF outcome in
women with TSH concentrations within normal adult range.
AB - BACKGROUND/AIMS: This study aimed to evaluate the association of thyroid
stimulating hormone (TSH) concentrations and presence of thyroid autoimmunity
(TAI) with the live birth rate in euthyroid women undergoing in vitro
fertilization (IVF). METHODS: This study of retrospective design included 158
euthyroid women (TSH 0.5-4.5 uIU/ml) who underwent IVF from January 2006 to
December 2010. Thyroid parameters were measured on day 3 of the previous
nontreatment cycle. Women were subgrouped and analyzed according to their TSH
concentrations (low: 0.5-2.5 vs. high: 2.6-4.5 uIU/ml) and TAI (present vs.
absent). RESULTS: No difference in the live birth rate was found between the TSH
(low: 34.2% vs. high: 36.8%, p = 0.763) or TAI (present: 26.7% vs. absent: 34.3%,
p = 0.568) subgroups. CONCLUSION: This study found no evidence that increased TSH
concentrations or the presence of TAI determined before IVF affect the live birth
rate in euthyroid women. A better insight into the role of thyroid function
during application of IVF is needed.
PMID- 24356284
TI - High-frequency oscillatory ventilation for early acute respiratory distress
syndrome in adults.
AB - PURPOSE OF REVIEW: High-frequency oscillatory ventilation (HFOV) has been
considered a potentially ideal mode of lung-protective ventilation. A recent meta
analysis suggested improved oxygenation and reduced mortality in adults and
children with acute respiratory distress syndrome (ARDS), but the use of outdated
control strategies and small numbers of patients in many of the studies rendered
these findings hypothesis-generating only. RECENT FINDINGS: During 2013, two
large randomized controlled trials comparing HFOV with a conventional lung
protective ventilation were published - the Oscillation for Acute Respiratory
Distress Syndrome Treated Early (OSCILLATE) and the Oscillation in ARDS (OSCAR)
trials. These trials suggested no benefit or even harm with HFOV in adults with
early moderate-to-severe ARDS. In this article, the major characteristics of
these two studies and the possible reasons for failure to achieve the expected
theoretical benefits are reviewed. Moreover, future directions with potential new
technical advances and the use of new bedside monitoring techniques are
addressed. SUMMARY: The OSCILLATE and OSCAR trials showed that the early
application of HFOV in moderate-to-severe adult ARDS does not reduce mortality
compared with conventional ventilation strategies. Future studies on HFOV will
need to identify those patients who might benefit most from HFOV and to determine
the best oscillator settings. Both goals require an improved capability of
monitoring recruitment and overdistension, and oscillatory volumes.
PMID- 24356285
TI - Influence of hypoxia in the intervertebral disc on the biological behaviors of
rat adipose- and nucleus pulposus-derived mesenchymal stem cells.
AB - Adipose-derived mesenchymal stem cells (ADMSCs) and nucleus pulposus-derived
mesenchymal stem cells (NPMSCs) are two cell candidates for cell-based therapies
for intervertebral disc (IVD) regeneration. However, little work has been done to
determine the influence of hypoxia in the IVD on the biological behaviors of
ADMSCs and NPMSCs. This study aimed to investigate the viability, proliferation
and differentiation of rat ADMSCs and NPMSCs in the hypoxic environment of IVD in
vitro. ADMSCs and NPMSCs isolated from 6 SD rats were cultured under normoxia
(20% O2) and hypoxia (2% O2) mimicking the standard condition and hypoxic
environment of the IVD for 14 days. Cell viability was determined by the annexin
V-FITC/propidium iodide double-staining assay and cell proliferation was measured
by MTT assay. The expression of hypoxia-inducible factor-1alpha, glucose
transporter (GLUT)-1, GLUT-3 and vascular endothelial growth factor-A at the mRNA
level was examined by RT-PCR. In cells cultured in three-dimensional micromass
and differentiation medium, aggrecan, collagen-II and Sox-9 expression at mRNA
and protein levels were examined by RT-PCR and Western blot. Hypoxia inhibited
the viability and proliferation of both ADMSCs and NPMSCs, but promoted the
chondrocytic differentiation of ADMSCs and NPMSCs. Compared to ADMSCs, NPMSCs
showed greater viability, proliferation and chondrocytic differentiation under
hypoxia. In conclusion, hypoxia in the IVD had a significant impact on the
viability, proliferation and chondrocytic differentiation of ADMSCs and NPMSCs.
NPMSCs exhibited more potent biological activity than ADMSCs in the hypoxic
environment of the IVD and may represent another candidate for cell-based therapy
for IVD regeneration.
PMID- 24356286
TI - [The Must of Endocrinology 2013. Editorial].
PMID- 24356287
TI - [Targeted therapies, prognostic and predictive factors in endocrine oncology].
AB - A better understanding of molecular mechanisms responsible for tumorigenesis has
allowed the development of targeted drugs designed to improve the outcome of
cancer. In endocrine tumors, several molecules have demonstrated efficacy in
terms of progression free survival during phase III trials such as vandetanib and
cabozantinib in medullary thyroid carcinoma, sorafenib in differentiated thyroid
carcinoma and everolimus or sunitinib for pancreatic neuroendocrine tumors. Rare
cancer network has allowed ongoing phase III trials in malignant pheochromocytoma
and adrenocortical carcinoma. However, to date no specific predictive biomarker
has yet been identified for a personalized cancer medicine. We review recent
advances in endocrine oncology concerning molecular targets identification,
targeted therapies and predictive or prognostic markers.
PMID- 24356288
TI - [Cushing's disease with negative imaging in adults].
AB - In more than one third of patients with Cushing's disease, pituitary MRI does not
identify a microadenoma. The diagnostic approach should be as rigorous as
possible in patients with ACTH-dependent Cushing's syndrome, to obtain a
definitive diagnosis. Improved pituitary MRI techniques, including dynamic
sequences, optimal T1-weighted spin-echo MRI protocol, MRI technique of spoiled
gradient recalled acquisition in the steady state, and using a 3-tesla magnet,
improved the tumor detection rate, parallel to the performance of endocrine
dynamic tests (CRH stimulation, desmopressin stimulation and high-dose
dexamethasone suppression tests). When a pituitary tumor is not convincingly
identified, inferior petrosal sinus sampling remains the gold standard for
diagnosis, and recently, new approaches (simultaneous prolactin measurement)
could improve its sensitivity and specificity. Transsphenoidal surgery is the
first-line treatment, with remission rates similar to those of patients with
preoperative positive MRI. However, medical therapies play an important role
after surgical failure or in a search for the onset of a visible tumor,
especially with development of new drugs targeting the pituitary gland.
PMID- 24356289
TI - [Aggressive and resistant-to-treatment pituitary tumors].
AB - Pituitary adenomas define slow growing tumors developing from anterior pituitary.
Most often benign, their treatment and subsequent management are based on
transphenoidal surgery and/or medical therapy, generally without difficulties in
clinical practice. However, 2 clinicopathological situations, more or less
intricated, may considerably complicate the management of these tumors and the
patient health condition. Firstly, when the tumor is characterized by an usual
aggressive behaviour with a possible extension within the cavernous sinus and a
high risk of recurence after well- conducted treatment. Otherwise, in some cases
of resistant prolactinomas and somatotropinomas, the specific medical treatment
may be unsuccessful for controlling the hormonal hypersecretion and/or the
tumoral growth, with subsequent complex therapeutic approach. Progress that have
been made in the understanding of aggressive as well as in resistant- to-
treatment pituitary tumors, both in histopathology and molecular fields, may
constitue new tools for improving knowledge on the profile of these atypical
tumors and optimizing their management.
PMID- 24356290
TI - [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].
AB - Normal human linear growth results from an evolutionary process expressing the
sum effect of multiple genes. The growth hormone (GH) - insulin like growth
factor (IGF)-I axis is one of the main actors in the growth process. Defects in
this axis can be responsible for short or tall stature. Short stature is defined
as smaller than - 2 standard deviations (SD). It is a very common reason for
consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple
causes make diagnosis difficult. In this article, we detail the most common
constitutional causes of small size, including those related to a defect in the
GH-IGF-I axis. Then, we report, the first results of the clinical and genetic
study conducted on 213 patients with gigantism. Tall stature is defined by a
height superior to 2 SD. Finally, recent work linking epigenetics and growth -
via signaling pathways of GH-IGF-I axis - will be presented.
PMID- 24356291
TI - [Hormonal dysnatremia].
AB - Because of antidiuretic hormone (ADH) disorder on production or function we can
observe dysnatremia. In the absence of production by posterior pituitary, central
diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal
dominant, autosomal recessive or X- linked forms. When ADH is secreted but there
is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in
acquired or hereditary form. We can make difference on AVP levels and/or on
desmopressine response which is negative in nephrogenic forms. Hyponatremia
occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar
hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate
secretion of ADH), a diagnostic of exclusion which is made after eliminating
corticotropin deficiency and hypothyroidism. In case of brain injury the
differential diagnosis of cerebral salt wasting (CSW) syndrome has to be
discussed, because its treatment is perfusion of isotonic saline whereas in
SIADH, the treatment consists in administration of hypertonic saline if
hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or
vaptans (antagonists of V2 receptors) can be used in some European countries.
Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome
of inappropriate antidiuresis) due to a constitutive activation of vasopressin
receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.
PMID- 24356292
TI - A prime time for trained immunity: innate immune memory in newborns and infants.
AB - The newborn and infant periods of early life are associated with heightened
vulnerability to infection. Limited antigen exposure and distinct adaptive immune
function compared to the adult places a greater burden on innate immunity for
host defense to microbial challenge during this time. Trained immunity describes
the phenomenon of augmented innate immune function following a stimulus that is
not specific to the original stimulus. We review the concept of trained immunity
in the context of the newborn's unique innate immune system function, the
preclinical and clinical evidence that supports the tenet of innate immune memory
in early life, and potential consequences of altered innate immune host
responses.
PMID- 24356293
TI - Fibroadenoma versus phyllodes tumor: distinguishing factors in patients diagnosed
with fibroepithelial lesions after a core needle biopsy.
AB - PURPOSE: We aimed to identify factors that might help differentiate phyllodes
tumors from fibroadenomas among cases in which a fibroepithelial breast lesion
was diagnosed from core needle biopsy (CNB) under imaging guidance. MATERIALS AND
METHODS: A retrospective review was performed on 213 lesions in 200 patients who
had undergone both CNB and excisional biopsy during a four-year period between
2008 and 2011. The final pathology revealed 173 fibroadenomas and 40 phyllodes
tumors. The data, including patient characteristics, clinical presentation, and
mammography, ultrasonography (US), and pathology findings were analyzed. RESULTS:
Upon univariable analysis, the factors that significantly helped to identify
phyllodes tumors consisted of the presenting symptoms (palpable mass or breast
pain), increased size on clinical examination, hyperdense mass on mammogram, and
the following three US features: heterogeneous echo, presence of round cysts
within the mass, and presence of clefts within the mass. The pathologist's
suggestion of a phyllodes tumor was also helpful. The factors that remained
statistically significant upon multivariable analysis consisted of symptoms of
breast pain, the presence of clefts on US, the presence of round cysts on US and
the pathologist's favoring of phyllodes tumors from a CNB specimen. CONCLUSION: A
multidisciplinary approach was needed to distinguish phyllodes tumors from
fibroadenomas in patients who had undergone CNB. US findings (clefts and round
cysts), suggestive pathological diagnoses, and clinical symptoms were all useful
for the decision to surgically remove the fibroepithelial lesions diagnosed from
CNB.
PMID- 24356294
TI - Follow-up of true visceral artery aneurysm after coil embolization by three
dimensional contrast-enhanced MR angiography.
AB - PURPOSE: We aimed to evaluate the outcomes of coil embolization of true visceral
artery aneurysms by three-dimensional contrast-enhanced magnetic resonance (MR)
angiography. MATERIALS AND METHODS: We used three-dimensional contrast-enhanced
MR angiography, which included source images, to evaluate 23 patients (mean age,
60 years; range, 28-83 years) with true visceral artery aneurysms (splenic, n=15;
hepatic, n=2; gastroduodenal, n=2; celiac, n=2; pancreaticoduodenal, n=1;
gastroepiploic, n=1) who underwent coil embolization. Angiographic aneurysmal
occlusion was revealed in all cases. Follow-up MR angiography was conducted with
either a 1.5 or 3 Tesla system 3-25 months (mean, 18 months) after embolization.
MR angiography was evaluated for aneurysmal occlusion, hemodynamic status, and
complications. RESULTS: Complete aneurysmal occlusion was determined in 22
patients (96%) on follow-up MR angiography (mean follow-up period, 18 months).
Neck recanalization, which was observed at nine and 20 months after embolization,
was confirmed in one of eight patients (13%) using a neck preservation technique.
In this patient, a small neck recanalization covered by a coil mass was
demonstrated. The complete hemodynamic status after embolization was determined
in 21 patients (91%); the visualization of several collateral vessels, such as
short gastric arteries, after parent artery occlusion was poor compared with that
seen on digital subtraction angiography in the remaining two patients (9%). An
asymptomatic localized splenic infarction was confirmed in one patient (4%).
CONCLUSION: Our study presents the follow-up results from three-dimensional
contrast-enhanced MR angiography, which confirmed neck recanalization, the
approximate hemodynamic status, and complications. This effective and less
invasive method may be suitable for serial follow-up after coil embolization of
true visceral aneurysms.
PMID- 24356295
TI - Feasibility of using vessel-detection software for the endovascular treatment of
visceral arterial bleeding.
AB - We aimed to investigate the feasibility of using vessel-detection software to
identify damaged arteries during endovascular embolization in five patients with
visceral arterial hemorrhages. We used a software program originally developed to
detect tumor feeder vessels in liver tumor embolization with C-arm computed
tomography datasets to detect the vessels responsible for the arterial
hemorrhages in patients with splenic artery pseudoaneurysms (n=2), lower
gastrointestinal bleeding (n=2), and bladder tumor bleeding (n=1). In all cases,
the injured vessel was identified accurately on a three-dimensional vascular map
at the optimal working angle with a relatively short mean processing time of 118
s (range, 107-136 s). The operating angiographers used this information to direct
the catheter into the damaged artery without sequential angiographic runs. The
software analysis was also used to plan coil delivery to the most appropriate
site in the injured artery. The results suggest that the vessel-detection
software for liver tumor embolization can also be used to detect damaged vessels
and to plan treatment strategies in endovascular embolization of visceral
arterial hemorrhage.
PMID- 24356297
TI - Clinical efficacy and safety of the combination of colistin plus vancomycin for
the treatment of severe infections caused by carbapenem-resistant Acinetobacter
baumannii.
AB - A potent synergy of a glycopeptide-colistin combination against Acinetobacter
baumannii has recently been described. We set out to assess the efficacy and
safety of this combination in a retrospective study including episodes of
ventilator-associated pneumonia or bacteremia caused by carbapenem-resistant A.
baumannii. We compared 29 patients (group I) treated with colistin plus
vancomycin with 28 patients treated with colistin alone (group II). Group I
received vancomycin (for empirical or targeted therapy) at the onset of colistin
administration and both antimicrobials coincided for at least 5 days. Baseline
characteristics, clinical cure, microbiological eradication, and mortality were
similar in both groups but the rate of acute kidney injury was higher in group I
(55.2 vs. 28%; p = 0.04). In critically ill patients with carbapenem-resistant A.
baumannii infections, clinical outcomes do not differ in patients treated with
colistin plus vancomycin from those receiving colistin without vancomycin. This
combination significantly increases the risk of renal failure.
PMID- 24356296
TI - Effect of the time to intervention on the outcome of thrombosed dialysis access
grafts managed percutaneously.
AB - PURPOSE: We aimed to investigate the effect of the time interval from the
clinical presentation of a thrombosed dialysis access graft to intervention on
procedure success. MATERIALS AND METHODS: Records from two academic institutions
for patients who underwent percutaneous thrombectomy of occluded surgical
hemodialysis graft access sites in interventional radiology from 2006 to 2011
were reviewed retrospectively. The following data were recorded: gender, age,
time and date of the initial request for a thrombectomy and the procedure, age of
the surgical access, angiographic outcome, and clinical outcome (successful or
unsuccessful postinterventional dialysis). Univariate and multivariate logistic
regression were used to evaluate whether the time to intervention significantly
affected the study endpoint. RESULTS: In total, 268 percutaneous thrombectomies
were performed in 139 patients. Of these 224 (83.5%) were categorized as
successful and 44 (16.4%) as unsuccessful. The time to intervention was 19.9+/
30.1 vs. 22+/-35 hours for successful and unsuccessful procedures, respectively.
The difference between the two was not significant, and there were also no
significant differences in covariate distributions between successful and
unsuccessful outcomes. CONCLUSION: During the first 72 hours following clinical
presentation of a thrombosed dialysis access graft, time to intervention may be
considered independent of procedure outcome.
PMID- 24356298
TI - Supramolecular catalysis. Part 1: non-covalent interactions as a tool for
building and modifying homogeneous catalysts.
AB - Supramolecular catalysis is a rapidly expanding discipline which has benefited
from the development of both homogeneous catalysis and supramolecular chemistry.
The properties of classical metal and organic catalysts can now be carefully
tailored by means of several suitable approaches and the choice of reversible
interactions such as hydrogen bond, metal-ligand, electrostatic and hydrophobic
interactions. The first part of these two subsequent reviews will be dedicated to
catalytic systems for which non-covalent interactions between the partners of the
reaction have been designed although mimicking enzyme properties has not been
intended. Ligand, metal, organocatalyst, substrate, additive, and metal
counterion are reaction partners that can be held together by non-covalent
interactions. The resulting catalysts possess unique properties compared to
analogues lacking the assembling properties. Depending on the nature of the
reaction partners involved in the interactions, distinct applications have been
accomplished, mainly (i) the building of bidentate ligand libraries (intra ligand
ligand), (ii) the building of di- or oligonuclear complexes (inter ligand
ligand), (iii) the alteration of the coordination spheres of a metal catalyst
(ligand-ligand additive), and (iv) the control of the substrate reactivity
(catalyst-substrate). More complex systems that involve the cooperative action of
three reaction partners have also been disclosed. In this review, special
attention will be given to supramolecular catalysts for which the observed
catalytic activity and/or selectivity have been imputed to non-covalent
interaction between the reaction partners. Additional features of these catalysts
are the easy modulation of the catalytic performance by modifying one of their
building blocks and the development of new catalytic pathways/reactions not
achievable with classical covalent catalysts.
PMID- 24356300
TI - AOPPs induce MCP-1 expression by increasing ROS-mediated activation of the NF
kappaB pathway in rat mesangial cells: inhibition by sesquiterpene lactones.
AB - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in
extracellular matrix accumulation through macrophage recruitment and activation
in the development and progression of diabetic nephropathy. Therefore, this study
examined whether advanced oxidation protein products (AOPPs) are involved in
nuclear factor-kappaB (NF-kappaB) activation and MCP-1 mRNA and protein
expression in mesangial cells (MCs) and evaluated the effects of derivatives of
sesquiterpene lactones (SLs) on AOPP-induced renal damage. METHODS: MCP-1 mRNA
and protein expression in MCs were determined by quantitative real-time PCR and
ELISA, respectively. The level of intracellular reactive oxygen species (ROS) was
determined by flow cytometry. The protein expression of tubulin, P47, NF-kappaB
p65, phospho-NF-kappaB p65, IkappaB, phospho-IkappaB, IKKbeta and phospho-IKKbeta
was evaluated by Western blot. RESULTS: AOPPs caused oxidative stress in MCs and
activated the NF-kappaB pathway by inducing IkappaBalpha phosphorylation and
degradation. Inhibition of ROS by SOD (ROS inhibitor) blocked the AOPP-mediated
NF-kappaB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP
1 mRNA and protein was associated with inhibition of IkappaBalpha degradation by
SLs. CONCLUSION: AOPPs induce MCP-1 expression by activating the ROS/NF-kappaB
pathway and can be inhibited by SLs. These findings may provide a novel approach
to treat inflammatory and immune renal diseases, including diabetic nephropathy.
PMID- 24356301
TI - A subclass B3 metallo-beta-lactamase found in Pseudomonas alcaligenes.
PMID- 24356302
TI - A natural prodrug activation mechanism in the biosynthesis of nonribosomal
peptides.
AB - Highlight describes the recently discovered prodrug activation mechanism found in
the biosynthesis of nonribosomally produced peptides and peptide/polyketide
hybrids as well as related mechanisms.
PMID- 24356303
TI - Prevalence and molecular characterization of Staphylococcus aureus colonization
among neonatal intensive care units in Taiwan.
AB - BACKGROUND: Staphylococcus aureus, particularly methicillin-resistant (MRSA), is
an important pathogen in neonatal intensive care units (NICUs). Carriage of S.
aureus is a significant risk factor for subsequent infection. OBJECTIVES: To
determine the current status of MRSA prevalence among NICU-hospitalized infants
in Taiwan, we conducted this pilot island-wide survey. METHODS: On two designated
dates in 2011, each patient who stayed in the NICUs of 7 participating hospitals
was included. Nasal and umbilical swabs were obtained and sent for detection of
S. aureus. The prevalence and risk factors for MRSA carriage were analyzed. MRSA
strains were tested for antimicrobial susceptibility and underwent molecular
characterization. RESULTS: A total of 251 subjects were included. The overall
prevalence of S. aureus and MRSA carriage was 13 and 4.4%, respectively. Previous
skin and soft tissue infection was the only predictor in multivariate analysis
(OR 40.36; 95% CI 2.32-702.64; p = 0.011). Among 11 MRSA isolates, 3 pulsotypes
were identified, with one major type (73%). Nine isolates carried a type IV
staphylococcal chromosomal cassette, and 2 carried the type VT. All but one MRSA
isolate belonged to linage sequence type 59, the community clone in Taiwan.
CONCLUSIONS: On a designated date, 4.4% of the infants staying in NICUs in Taiwan
carried almost genetically identical community strains of MRSA. MRSA colonization
in these infants was significantly associated with previous skin and soft tissue
infection.
PMID- 24356304
TI - A database and website for molecular defects of the GH-IGF axis:
www.growthgenetics.com.
AB - BACKGROUND/AIMS: Over the last decade, multiple molecular defects of the GH-IGF
axis have been identified and characterized, greatly expanding our appreciation
of the genotypic and phenotypic variability of endocrine growth disorders.
METHODS: In an effort to address the growing complexity of molecular defects and
their characteristic phenotypes, a Growth Genetics Consortium was established in
2008, with the goal of developing a repository of case information on all
patients with genetic variations in the GH-IGF axis. A database was established,
along with a publicly accessible website (www.growthgenetics.com), with
registration open to all potential users. RESULTS: The genes currently available
in the database include GHR, Stat5b, IGF1, IGF2, IGFALS and IGF1R. The data
collected include clinical details, auxology, family history, laboratory data,
identified molecular defects and, if relevant, treatment information.
CONCLUSIONS: It is planned for the database and website to eventually include all
identified genes in the GH-IGF axis.
PMID- 24356305
TI - Why are people afraid of the dentist? Observations and explanations.
AB - OBJECTIVE: The aim of this review was to explore the peer-reviewed literature to
answer the question: 'Why are people afraid of the dentist?' METHOD: Relevant
literature was identified by searching the following on-line databases: PubMed,
PsycInfo, the Cochrane Library and Google Scholar. Publications were extracted if
they explored the causes and consequences of dental fear, dental anxiety or
dental phobia. RESULTS: The research evidence suggests that the causes of dental
fear, dental anxiety or dental phobia are related to exogenous factors such as
direct learning from traumatic experiences, vicarious learning through
significant others and the media, and endogenous factors such as inheritance and
personality traits. Each individual aetiological factor is supported by the
evidence provided. CONCLUSIONS: The evidence suggests that the aetiology of
dental fear, anxiety or phobia is complex and multifactorial. The findings show
that there are clear practical implications indicated by the existing research in
this area: a better understanding of dental fear, anxiety and phobia may prevent
treatment avoidance.
PMID- 24356307
TI - Formant transitions in varied utterance positions.
AB - AIM: Acoustic characteristics associated with varied utterance positions were
examined to understand the acoustic consequences of potential articulatory
changes near utterance boundaries. METHODS: Second formant transition
characteristics, including transition duration (ms), transition extent (Hz), and
derived slope of transition (Hz/ms), of 12 healthy speakers of American English
were examined for two diphthong transitions in sew and sigh and one consonant
vowel transition in bee in utterance-initial, utterance-final, and utterance-end
positions. Speakers performed a task of contrastive stress variation that served
to demonstrate the changeability of acoustic characteristics as an index of
articulatory change in shaping the vocal tract. RESULTS: Contrastive stress, as
compared to words spoken without increased stress, was associated with longer
transition duration, greater transition extent, and a decreased slope. Although
some utterance position effects were present, no systematic differences
consistent with boundary strengthening or declination were found. CONCLUSION:
Findings suggest that varied utterance positions may be associated with stimulus
dependent variation in articulatory changes that is reflected in the acoustic
output. These results indicate the need to further understand the construct of
utterance-level speech materials, such as carrier phrases, in clinical practice
and research.
PMID- 24356306
TI - Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection.
AB - The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly
understood although apoptosis has been proposed as a key mechanism. We now show
that caspase-3-mediated apoptosis accounts for the death of only a small fraction
of CD4 T cells corresponding to those that are both activated and productively
infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase
1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis
corresponds to an intensely inflammatory form of programmed cell death in which
cytoplasmic contents and pro-inflammatory cytokines, including IL-1beta, are
released. This death pathway thus links the two signature events in HIV infection
CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious
cycle in which dying CD4 T cells release inflammatory signals that attract more
cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe
in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics
targeting the host rather than the virus.
PMID- 24356308
TI - C-terminal agrin fragment--a new fast biomarker for kidney function in renal
transplant recipients.
AB - BACKGROUND: The C-terminal agrin fragment (CAF) is a cleavage product of agrin,
the major proteoglycan of the glomerular basement membrane. This article studies
if CAF could serve as a biomarker for renal function in renal transplant
recipients. MATERIAL AND METHODS: We measured serum CAF and creatinine
concentrations and calculated estimated glomerular filtration rate (eGFR) (MDRD)
in 96 healthy individuals and in 110 end-stage renal disease patients undergoing
kidney transplantation before and after transplantation. Correlation between CAF
and creatinine concentrations/eGFR was calculated as within-patient (cWP) and
between-patient correlations (cBP). Moreover, we evaluated the association of CAF
with delayed graft function (DGF). The diagnostic value of CAF for early
detection of DGF compared to creatinine was evaluated by receiver operating
characteristics (ROC) analysis. RESULTS: CAF concentrations strongly correlated
with creatinine (r = 0.86 (cWP), r = 0.74 (cBP)) and eGFR (MDRD) (r = 0.86 (cWP),
r = 0.77 (cBP)). Pre-transplant (pre-Tx) CAF concentrations were 19-fold higher
than in healthy individuals (1,115.0 (258.4-3,990.0) vs. 56.6 (20.0-109.5) pM).
After transplantation, CAF decreased significantly faster than creatinine
(postoperative days 1-3 (POD 1-3): 562.8 (101.6-2,113.0) pM; creatinine: pre-Tx
6.9 (3.1-15.7), POD 1-3: 6.4 (1.7-12.7) mg/dl, p < 0.001). Stable concentrations
were reached 1-3 months after transplantation for CAF and creatinine (CAF 145.1
(6.7-851.0) pM; creatinine 1.6 (0.7-8.0) mg/dl). CAF concentrations at POD 1-3
were significantly associated with DGF and outperformed creatinine in early
detection of DGF (area under the curve (AUC) CAF 80.7% (95% CI 72.3-89.1%) vs.
AUC creatinine 71.3% (95% CI 61.8-81.1%), p = 0.061). CONCLUSION: CAF is a
promising new and fast biomarker for kidney function and may serve as a new tool
for the early detection of DGF.
PMID- 24356309
TI - Single domain SmCo5@Co exchange-coupled magnets prepared from core/shell
Sm[Co(CN)6].4H2O@GO particles: a novel chemical approach.
AB - SmCo5 based magnets with smaller size and larger maximum energy product have been
long desired in various fields such as renewable energy technology, electronic
industry and aerospace science. However, conventional relatively rough synthetic
strategies will lead to either diminished magnetic properties or irregular
morphology, which hindered their wide applications. In this article, we present a
facile chemical approach to prepare 200 nm single domain SmCo5@Co core/shell
magnets with coercivity of 20.7 kOe and saturation magnetization of 82 emu/g. We
found that the incorporation of GO sheets is responsible for the generation of
the unique structure. The single domain SmCo5 core contributes to the large
coercivity of the magnets and the exchange-coupled Co shell enhances the
magnetization. This method can be further utilized in the synthesis other Sm-Co
based exchange-coupled magnets.
PMID- 24356310
TI - Moving our agenda forward.
PMID- 24356311
TI - Perspectives on pediatric physical therapy education.
AB - PURPOSE: The Section on Pediatrics convened an Education Summit in July 2012 to
examine, discuss, and respond to documented inconsistencies and challenges in
teaching pediatric physical therapy content in entry-level professional education
programs. This lecture was designed to provide attendees with the history of
pediatric physical therapy education, stemming from the author's early
involvement with the Section on Pediatrics and as a long-standing academician.
SUMMARY OF KEY POINTS: The limited literature on pediatric physical therapy
education was reviewed and used to highlight the continued variability across
programs. The challenge was presented to build upon attendees' scholarship of
teaching and learning. STATEMENT OF CONCLUSIONS: These remarks were designed to
help understand the growth and development in pediatric physical therapy
education over the past 40 years and to encourage others to use what has been
learned to build a stronger foundation for the future.
PMID- 24356312
TI - Essential competencies in entry-level pediatric physical therapy education.
AB - BACKGROUND: The Section on Pediatrics (SoP) convened an Education Summit in July
2012 to examine, discuss, and respond to documented inconsistencies and
challenges in teaching pediatric physical therapy (PT) content in entry-level
professional education programs. Despite previous attempts by the SoP to provide
guidance around teaching pediatric PT, variability continued to be extensive
across programs. KEY POINTS: This article presents the core competencies
developed out of the Summit to inform pediatric content in the entry-level PT
curriculum. In addition, the core competencies were linked to teaching
strategies, learning activities, assessment outcomes, and curricular structures.
STATEMENT OF CONCLUSIONS: Consensus was reached on 5 core competencies that
represent a knowledge base essential to all graduates of PT programs. In contrast
to prior SoP documents, these competencies were specifically designed to focus on
knowledge and skills unique to pediatric practice but essential for all graduates
of accredited entry-level PT education programs. VIDEO ABSTRACT: For more
insights from the authors, see Supplemental Digital Content 1, at
http://links.lww.com/PPT/A50.
PMID- 24356313
TI - Physical activity of children with a mitochondrial disease compared to children
who are healthy.
AB - PURPOSE: To compare the physical activity of a group of children with
mitochondrial myopathy (MM) with children who are healthy and to evaluate the
suitability of different measurement tools. METHODS: The physical activity of 6
children with MM and 10 children who are healthy was measured using
accelerometry, heart rate monitoring, video observation, rating of their fatigue,
and 2 questionnaires about their physical activity and quality of life. RESULTS:
The children with MM spent less time in moderate to vigorous activity, and their
activity level measured with the accelerometer was lower than the children who
are healthy. Also, the children with MM indicated a higher level of fatigue and a
lower quality of life. CONCLUSIONS: Children with MM are on average less
physically active, report a higher level of fatigue, and a lower quality of life
than children who are healthy.
PMID- 24356314
TI - Commentary on "Physical activity of children with a mitochondrial disease
compared to children who are healthy".
PMID- 24356315
TI - Effect of body-scaled information on reaching in children with hemiplegic
cerebral palsy: a pilot study.
AB - PURPOSE: This study examined body-scaled information that specifies the reach
patterns of children with hemiplegic cerebral palsy and children with typical
development. METHODS: Nine children with hemiplegic cerebral palsy (3-5 years)
and 9 age-matched children with typical development participated in the study.
They were required to reach and grasp 10 different pairs of cubes. Reach data
were coded as either a 1-handed reach or a 2-handed reach. Dimensionless ratios
were calculated by dividing the cube size by the maximal aperture between the
index finger and thumb. A critical ratio was used to establish the shift from a 1
handed to an exclusive 2-handed reach. RESULTS: The critical ratio was not
significantly different for either preferred or nonpreferred arms within and
between groups. All children used an exclusive 2-handed reach at a similar
dimensionless ratio. CONCLUSION: Our study provides evidence of the "fit" between
environment (cube size) and the individual's capabilities (finger aperture) for
reaching for both groups.
PMID- 24356316
TI - Commentary on "Effect of body-scaled information on reaching in children with
hemiplegic cerebral palsy: a pilot study".
PMID- 24356317
TI - Efficacy of orthoses for children with hypotonia: a systematic review.
AB - PURPOSE: The purpose of this systematic review of the literature was to determine
the efficacy of orthoses for children with hypotonia and provide a concise
summary of the state of the evidence in this area. METHODS: Fifteen search terms
were used to find articles addressing children with hypotonia, orthotic use, and
physical therapy. RESULTS: Ten articles met the inclusion criteria, but no level
I evidence was found. Data were reported for body structure and activity
components, but not participation outcomes. Current evidence suggests that foot
orthoses and supramalleolar orthoses may benefit children with hypotonia;
however, the evidence is low level. CONCLUSION: The evidence for efficacy of
orthoses for children with hypotonia continues to have gaps with the following
questions still unanswered: When is the optimal time to introduce orthoses? Are
foot orthoses or supramalleolar orthoses more efficacious? Should orthoses be
combined with physical therapy?
PMID- 24356318
TI - Assessing gross motor development of Brazilian infants.
AB - PURPOSE: To determine whether the Alberta Infant Motor Scale (AIMS) requires
reference values specific for Brazilian infants. METHODS: A total of 660 (330
girls) healthy full-term infants from Belo Horizonte were assessed using the
AIMS. Scores and percentile curves were compared with the Canadian reference
values. RESULTS AND DISCUSSION: Differences were found in the 5th percentile (9
<10 and 10-<11 months) and the 10th percentile (4-<5, 9-<10, and 10-<11 months)
curves. No significant differences were found between sexes on the basis of the
economic classification or the criteria of the Human Development Index.
CONCLUSION: Primarily because of the corrections made to the 5th and 10th
percentile curves, we recommend the use of the Brazilian infant data curves
reported here for further studies conducted in Brazil. Because the Human
Development Index of Belo Horizonte is similar to that for Brazil as a whole, the
results of this study should be relevant for clinicians throughout Brazil.
PMID- 24356319
TI - Commentary on "Assessing gross motor development of Brazilian infants".
PMID- 24356320
TI - Accommodating the Bayley-III for motor and/or visual impairment: a comparative
pilot study.
AB - PURPOSE: This study assessed the validity and usefulness of the Bayley Scales of
Infant and Toddler Development, Third Edition (Bayley-III) Low Motor/Vision
accommodated version. Accommodations are adaptations to minimize impairment bias,
without altering what the test measures. Of the items, 66% have Low Motor
accommodations like enlarged materials; 62% have Low Vision accommodations.
METHODS: Using a within-subject design, we tested 19 children with the
accommodated and standard Bayley-III, in a randomly counterbalanced order. The
children had motor and/or visual impairment and a chronological age between 22
and 90 months. The test administrators completed an evaluation form. RESULTS: A
subgroup of children benefited from the accommodations; 2 children obtained a
large raw score difference. Test administrators considered the accommodations as
practical, and advantageous for most children. CONCLUSION: The Low Motor/Vision
accommodated version seems to validly assess the development of this population.
Future, larger-scale research should study whether the accommodations improve the
construct validity of the Bayley-III.
PMID- 24356321
TI - Commentary on "Accommodating the Bayley-III for motor and/or visual impairment: a
comparative pilot study".
PMID- 24356322
TI - Motor competence and physical fitness in adolescents.
AB - PURPOSE: In this study we examined the relationship between physical fitness and
motor competence in adolescents aged 15 to 16 years. METHODS: A sample of 94
adolescents participated in the study. To test motor competence, the Movement
Assessment Battery for Children-2 was used. Physical fitness was assessed using
the following test items: standing broad jump, 20-m dash, reduced Cooper test,
and sit-and-reach test. RESULTS: The results revealed a significant but weak
relationship (0.248) between motor competence and physical fitness for the whole
sample. More specifically, the correlation between the 2 variables was
significant for girls (0.353) but not for boys (0.248). CONCLUSIONS: The
relatively weak relationship between motor competence and physical fitness
suggests that motor competence might not be critical in adolescents to maintain
their physical fitness.
PMID- 24356323
TI - Commentary on "Motor competence and physical fitness in adolescents".
PMID- 24356324
TI - Physical therapy for a child with sudden-onset choreoathetosis: a case report.
AB - PURPOSE: This case report describes the physical therapy examination,
intervention, and outcomes for a 5-year-old girl who developed choreoathetosis
following mitral valve repair. CASE DESCRIPTION: This child was admitted to an
inpatient short-term rehabilitation program with marked choreoathetosis and
dependence for all functional mobility. She received physical therapy twice a day
for 5 weeks. Physical therapy intervention included therapeutic exercise
emphasizing stabilization and closed chain exercises, aquatic therapy, and
functional training to improve gross motor skills and mobility. Tests and
measures included the Selective Control Assessment of the Lower Extremity, 66
item Gross Motor Function Measure, and Pediatric Evaluation of Disability
Inventory. OUTCOMES: At discharge, this child demonstrated improvements in her
Selective Control Assessment of the Lower Extremity, Gross Motor Function
Measure, and Pediatric Evaluation of Disability Inventory scores. She was
independent in all functional mobility tasks. SUMMARY: This case study describes
physical therapy tests and measures, intervention, and positive outcomes for a
child with sudden-onset choreoathetosis.
PMID- 24356326
TI - Age-related macular degeneration screening using a nonmydriatic digital color
fundus camera and telemedicine.
AB - PURPOSE: To investigate the use of a nonmydriatic digital color fundus camera and
telemedicine as screening tools for age-related macular degeneration (AMD).
METHODS: Nonmydriatic color fundus photography was performed on patients
consulting health examination centers and transmitted by telemedicine to an
ophthalmology department. Rates for different grades of AMD were calculated and
also statistically related to the presence or absence of risk factors. RESULTS:
Among the 1,022 patients screened, a total of 1,363 color fundus photographs were
interpreted, with 80% gradable images, allowing a diagnosis of AMD in 178
photographs. Among all the gradable images, 83.7% had no AMD (grade 0). The rates
of AMD at grades 1, 2, 3 and 4 were 8%, 5.6%, 2.3% and 0.4%, respectively. A
statistical odds ratio was found between the presence of AMD on fundus
photographs and age, familial history of AMD or prior cataract surgery.
CONCLUSIONS: Nonmydriatic color fundus photography and telemedicine succeeded in
screening for AMD.
PMID- 24356325
TI - CCK1-receptor stimulation protects against gut mediator-induced lung damage
during endotoxemia.
AB - BACKGROUND/AIMS: Cholecystokinin 1-receptor (CCK1-R) activation by long chain
fatty acid (LCFA) absorption stimulates vago-vagal reflex pathways in the brain
stem. The present study determines whether this reflex also activates the
cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine
release during endotoxemia. METHODS: Mesenteric lymph was obtained from wild type
(WT) and CCK1-R knockout (CCK1-R(-/-)) mice intraperitoneally challenged with
Lipopolysaccharid (LPS) (endotoxemic lymph, EL) and intestinally infused with
vehicle or LCFA-enriched solution. The lymph was analyzed for TNFalpha, IL-6 and
IL-10 concentration and administered to healthy recipient mice via jugular
infusion. Alveolar wall thickness, myeloperoxidase (MPO) and TUNEL positive cells
were determined in lung tissue of recipient mice. RESULTS: LCFA infusion in WT
mice reduced TNFalpha concentration in EL by 49% compared to vehicle infusion,
but had no effect in CCK1-R(-/-) mice. EL significantly increased the alveolar
wall thickness, the number of MPO-positive and TUNEL-positive cells compared to
control lymph administration. LCFA infusion in WT, but not in CCK1R(-/-) mice,
significantly reduced these pathological effects of EL. CONCLUSION: During
endotoxemia enteral LCFA absorption reduces TNFalpha release into mesenteric
lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to
elicit this effect in CCK1R(-/-) mice demonstrates that anti-inflammatory
properties of LCFAs are mediated through CCK1-Rs.
PMID- 24356327
TI - Epidemiology of HIV in Latin America and the Caribbean.
AB - PURPOSE OF REVIEW: The aim of the present review is to update HIV/AIDS
Epidemiology in Latin America and the Caribbean highlighting the concentrated
aspect of epidemic in the region. RECENT FINDINGS: Among general population, HIV
prevalence in Latin America is at stable levels (0.2-0.7%). The Caribbean still
has one of the highest HIV prevalence rates in the world (<0.1-3%), but
incidences have declined around 49%. This is not the current situation for high
risk key populations; most incident cases occur among MSM. Available data on
transgender women suggest that they are the most-at-risk group. Female sex
workers still have a 12-fold the chance of being HIV positive compared with other
women. IDU prevalence was revised to 0.45%, but non-IDU has been suggested as a
mediator between sexual risk and HIV. SUMMARY: The increase in treatment coverage
(mean is at 63%) resulted in modifications of HIV/AIDS epidemiology. New
strategies to seek, test and link key populations to care are urgently needed and
targeted interventions to prevent HIV expansion among them must be adopted. These
strategies should consider the particular situation regarding social
inequalities, discrimination and violence that pervade the HIV epidemic among key
populations.
PMID- 24356328
TI - Concentrated HIV subepidemics in generalized epidemic settings.
AB - PURPOSE OF REVIEW: A relatively neglected topic to date has been the occurrence
of concentrated epidemics within generalized epidemic settings and the potential
role of targeted interventions in such settings. We review recent studies in high
risk groups as well as findings relating to geographical heterogeneity and the
potential for targeting 'high-transmission zones' in the 10 countries with
highest HIV prevalence. RECENT FINDINGS: Our review of recent studies confirmed
earlier findings that, even in the context of generalized epidemics, MSM have a
substantially higher prevalence than the general population. Estimates of
prevalence of HIV among people who inject drugs (PWID) in sub-Saharan African
countries are rarely available and, when they are, often outdated. We identified
recent studies of sex workers in Kenya and Uganda. In all three cases - MSM,
PWID, and sex workers - HIV prevalence estimates are mostly based on convenience.
Moreover, good estimates of the total size of these populations are not
available. Our review of recent studies of high-risk populations defined on the
basis of geography showed high levels of both new and existing infections in
Kenya (slums), South Africa (peri-urban communities), and Uganda (fishing
villages). SUMMARY: Recent empirical findings combined with evidence from
phylogenetic studies and supported by mathematical models provide a clear
rationale for testing the feasibility, acceptability, and effectiveness of
targeted HIV prevention approaches in hyperendemic populations to supplement
measures aimed at the general population.
PMID- 24356330
TI - Time resolved emission at 1.3 MUm of a single InAs quantum dot by using a tunable
fibre Bragg grating.
AB - Photoluminescence and time resolved photoluminescence from single metamorphic
InAs/GaAs quantum dots (QDs) emitting at 1.3 MUm have been measured by means of a
novel fibre-based characterization set-up. We demonstrate that the use of a
wavelength tunable fibre Bragg grating filter increases the light collection
efficiency by more than one order of magnitude as compared to a conventional
grating monochromator. We identified single charged exciton and neutral biexciton
transitions in the framework of a random population model. The QD recombination
dynamics under pulsed excitation can be understood under the weak quantum
confinement potential limit and the interaction between carriers at the wetting
layer and QD states.
PMID- 24356329
TI - Use of a text message program to raise type 2 diabetes risk awareness and promote
health behavior change (part I): assessment of participant reach and adoption.
AB - BACKGROUND: There are an estimated 25.8 million American children and adults,
equivalent to 8.3% of the US population, living with diabetes. Diabetes is
particularly burdensome on minority populations. The use of mobile technologies
for reaching broad populations is a promising approach, given its wide footprint
and ability to deliver inexpensive personalized messages, to increase awareness
of type 2 diabetes and promote behavior changes targeting risk factors associated
with type 2 diabetes. As a part of the Beacon Community Cooperative Agreement
Program, txt4health, a public-facing mobile health information service, was
launched in 3 Beacon Communities: the Southeast Michigan Beacon Community in
Detroit, MI, the Greater Cincinnati Beacon Community in Cincinnati, OH, and the
Crescent City Beacon Community in New Orleans, LA. Txt4health is a mobile health
information service designed to help people understand their risk for type 2
diabetes and become more informed about the steps they can take to lead healthy
lives. OBJECTIVE: The purpose of this investigation was to use the RE-AIM
framework to document txt4health reach and adoption by focusing on enrollment and
participant engagement in program pilots in Southeast Michigan and Greater
Cincinnati. METHODS: We conducted a retrospective records analysis of individual
level txt4health system data from participants in Southeast Michigan and Greater
Cincinnati to determine participant usage of txt4health and engagement with the
program. RESULTS: Results from the retrospective records analysis revealed that
5570 participants initiated the 2-step enrollment process via 1 of 3 enrollment
strategies: text message, website, or directly with Beacon staff who signed
participants up via the website. In total, 33.00% (1838/5570) of participants
completed the 2-step enrollment process and were fully enrolled in the program.
All participants (100.00%, 1620/1620) who enrolled via text message completed the
entire 2-step enrollment process versus 5.52% (218/3950) of participants who
enrolled via website or a Beacon staff member. Of those who fully enrolled,
71.00% (1305/1838) completed the diabetes risk assessment and 74.27% (1365/1838)
set an initial weight loss goal. Overall, 39.06% (718/1838) of participants
completed all 14 weeks of the program and 56.26% (1034/1838) dropped out before
completing all 14 weeks, with the bulk of dropouts occurring in the first 4
weeks. Length of participation varied greatly, ranging from 0-48.7 weeks (median
8.6, mean 15.8, SD 15.8). Wide variability of participant engagement in regards
to weekly weight and physical activity was documented. CONCLUSIONS: Although
broadly focused public health text message interventions may have the potential
to reach large populations and show high levels of engagement among some users,
the level of individual engagement among participants varies widely, suggesting
that this type of approach may not be appropriate for all.
PMID- 24356331
TI - ADHD symptoms across the lifespan: a comparison of symptoms captured by the
Wender and Barkley Scales and DSM-IV criteria in a population-based Swedish
sample aged 65 to 80.
AB - OBJECTIVE: The aim was to compare different scales capturing ADHD symptoms for
older individuals' self-reports about childhood and current ADHD symptomatology.
An additional aim was relating these results to the Diagnostic and Statistical
Manual of Mental Disorders (4th ed.; DSM-IV) ADHD criteria. METHOD: The 25-item
Wender Utah Rating Scale (WURS) administered in a population-based sample of
1,599 individuals aged 65 to 80. Two subsamples each with 30 individuals were
randomly drawn based on their Wender Utah Rating Scale (WURS) scores, and studied
using the Wender Riktad ADHD Symtom Skala (WRASS), interview assessed Barkley
Scales, and DSM-IV ADHD criteria. RESULTS: Higher WURS and WRASS scores were
related to higher Barkley Childhood and Current Symptoms Scales Scores. Also,
reporting more symptoms on these scales was related to meeting DSM-IV criteria
for childhood and current ADHD. CONCLUSION: The results support significant
persistence of ADHD symptoms when using different scales designed for the capture
of childhood and current ADHD symptomatology. Further studies of ADHD in a
lifespan perspective are encouraged.
PMID- 24356332
TI - Perinatal outcomes of pregnancies complicated by maternal depression with or
without selective serotonin reuptake inhibitor therapy.
AB - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly
prescribed psychotropics for major depressive disorder during pregnancy and are
used in up to 6.2% of pregnancies. OBJECTIVE: To compare the perinatal outcomes
of pregnancies complicated by maternal depression with or without SSRI therapy
versus nondepressed pregnancies. METHODS: International Classification of
Diseases (ICD)-9 codes for depression were identified among women who delivered
at the University of Iowa from April 2009 to March 2011. Data were extracted from
linked maternal-neonatal records for all charts with an ICD-9 code for depression
and an equal number of women without ICD-9 codes for depression. RESULTS: Of the
3,695 women who delivered between 2009 and 2011, 238 had an ICD-9 code for
depression. Sixteen women had depression listed in their records but did not have
an ICD-9 code for depression. Their data were combined with those of the women
with ICD-9 codes for depression, and it was found that 126 women (50%) in this
combined depression cohort received an SSRI. Women with depression had increased
alcohol and tobacco use, BMI and premature delivery rates (p < 0.01). Maternal
depression was associated with an increased frequency of neonatal intensive care
unit (NICU) admission (p < 0.001). In addition to depression, maternal SSRI use,
obesity and smoking were univariate predictors of NICU admission. CONCLUSIONS:
Among women with depression, the use of an SSRI was not associated with
significant differences in any of the measured maternal or neonatal parameters,
but further studies are needed to evaluate the specific effects of SSRI exposure
in early or late gestation. Despite SSRI utilization, women with depression
continue to have increased risks during pregnancy.
PMID- 24356334
TI - Transcriptomic analysis of sexual differentiation in somatic tissues of
Drosophila melanogaster: successes and caveats.
AB - The advent of high-throughput technologies to analyze RNA expression levels and
transcript structure has brought renewed attention to the age-old question of
what differentiates males from females. In Drosophila, the characterized somatic
sex determination cascade includes proteins implicated in the regulation of pre
mRNA splicing as well as at least 2 transcription factors at its base. Both DNA
microarrays and RNA-Seq have been applied in a number of studies to determine the
identities, expression levels and structure of transcripts expressed
differentially in the 2 sexes, with remarkably divergent results in the number,
structure and identity of affected transcripts. We briefly summarize these
reports and discuss the reasons for the apparent discrepancies based upon the
different conditions used for sample preparation and data analysis.
PMID- 24356333
TI - Gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line
chemotherapy for advanced biliary tract cancer: a retrospective cohort study.
AB - BACKGROUND AND AIM: Gemcitabine plus cisplatin (GP) is a standard chemotherapy
option for patients with advanced biliary tract cancer (BTC). We compared the
efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced
BTC. METHODS: The records of all patients treated with GP or XP chemotherapy for
unresectable, metastatic, or recurrent BTC at the National Cancer Center between
December 2001 and August 2012 were reviewed retrospectively. Patients with
histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or
extrahepatic cholangiocarcinoma were enrolled. RESULTS: Of the 344 patients
enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9
months, the median time to progression was longer in the GP group than in the XP
group (5.6 vs. 4.7 months), but the difference was not statistically significant
(p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in
the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with
statistical significance retained following multivariate analysis (HR 0.72; 95%
CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent
in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). CONCLUSIONS: GP
was superior to XP in prolonging OS, despite increasing the rate of grade 3/4
adverse events.
PMID- 24356335
TI - Morphology-dependent nanocatalysts: rod-shaped oxides.
AB - Nanocatalysts are characterised by the unique nanoscale properties that originate
from their highly reduced dimensions. Extensive studies over the past few decades
have demonstrated that the size and shape of a catalyst particle on the nanometre
scale profoundly affect its reaction performance. In particular, controlling the
catalyst particle morphology allows a selective exposure of a larger fraction of
the reactive facets on which the active sites can be enriched and tuned. This
desirable surface coordination of catalytically active atoms or domains
substantially improves catalytic activity, selectivity, and stability. This
phenomenon is called morphology-dependent nanocatalysts: catalyst particles with
anisotropic morphologies on the nanometre scale greatly affect the reaction
performance by selectively exposing the desired facets. In this review, we
highlight important progress in morphology-dependent nanocatalysts based on the
use of rod-shaped metal oxides with characteristic redox and acid-base features.
The correlation between the catalytic properties and the exposed facets verifies
the chemical nature of the morphology effect. Moreover, we provide an overview of
the interactions between the rod-shaped oxides and the metal nanoparticles in
metal-oxide catalyst systems, involving crystal-facet-selective deposition of
metal particles onto different crystal facets in the oxide supports. A
fundamental understanding of active sites in morphologically tuneable oxides
enclosed by the desired reactive facets is expected to direct the development of
highly efficient nanocatalysts.
PMID- 24356336
TI - Male germ cell development in humans.
AB - BACKGROUND: Germ cells are unique cells that possess the ability to transmit
genetic information between generations. Detailed knowledge about the molecular
and cellular mechanisms determining the fate of human male germ cells still
remains sparse. This is partially due to ethical issues limiting the access to
research material. Therefore, the mechanisms of proliferation, differentiation
and apoptosis of human male germ cells still remain challenging study objectives.
METHODS: This review focuses on using English articles accessible in PubMed as
well as personal files on the current knowledge of the molecular and cellular
mechanisms connected with human testicular germ cell development, maturation
failure and the possibility of fertility preservation in patients in whom there
is a risk of gonadal failure. However, since rodents, particularly mice, offer
the possibility of studying germ cell development by use of genetic modification
techniques, some studies using animal models are also discussed. CONCLUSION: This
mini review focuses on the current knowledge about male germ cells. However, the
reader is referred to two previous mini reviews focusing on testicular somatic
cells, i.e. on Sertoli cells and Leydig cells.
PMID- 24356338
TI - Effects of age and gender in normal-speaking children on the nasality severity
index: an objective multiparametric approach to hypernasality.
AB - OBJECTIVE: Since resonance disorders have a multidimensional nature and occur in
several craniofacial pathologies, the aim of the present study was to determine
the influence of age and gender in normal-speaking children without resonance
disorders on an objective multiparametric index of hypernasality. PATIENTS AND
METHODS: A total of 74 Flemish children (37 boys and 37 girls), aged 4-12 years,
without resonance disorders were included. A Nasometer was used to obtain
nasalance scores (1 phoneme, 2 reading passages). An aerodynamic value was
calculated using maximum duration time, and the mirror-fogging test by Glatzel
was applied to visualize nasality as measured by condensation. With the obtained
results, a 'Nasality Severity Index' (NSI) was calculated. RESULTS: A significant
age effect was found, in which the NSI increased with increasing age (p < 0.001).
No significant difference for the NSI was detected concerning gender (p > 0.05).
Unfortunately, considerable standard deviations from the mean NSI were found.
CONCLUSION: Although a multiparametric index can form a more powerful approach in
the assessment of and treatment planning for individuals with hypernasality, the
present study revealed large interindividual differences in the current NSI.
Therefore, adaptation of the current NSI is recommended, by which the influences
of personal and environmental variables are taken into account.
PMID- 24356337
TI - pH dependent transfer of nano-pores into membrane of cancer cells to induce
apoptosis.
AB - Proper balance of ions in intracellular and extracellular space is the key for
normal cell functioning. Changes in the conductance of membranes for ions will
lead to cell death. One of the main differences between normal and cancerous
cells is the low extracellular pHe and the reverse pH gradient: intracellular pHi
is higher than extracellular pHe. We report here pH-selective transfer of nano
pores to cancer cells for the dis-regulation of balance of monovalent cations to
induce cell death at mildly acidic pHe as it is in most solid tumors. Our
approach is based on the pH-sensitive fusion of cellular membrane with the
liposomes containing gramicidin A forming cation-conductive beta-helix in the
membrane. Fusion is promoted only at low extracellular pH by the pH (Low)
Insertion Peptide (pHLIP(r)) attached to the liposomes. Gramicidin channels
inserted into the cancer cells open flux of protons into the cytoplasm and
disrupt balance of other monovalent cations, which induces cell apoptosis.
PMID- 24356339
TI - Low integrated DNA repair score and lung cancer risk.
AB - DNA repair is a prime mechanism for preventing DNA damage, mutation, and cancers.
Adopting a functional approach, we examined the association with lung cancer risk
of an integrated DNA repair score, measured by a panel of three enzymatic DNA
repair activities in peripheral blood mononuclear cells. The panel included
assays for AP endonuclease 1 (APE1), 8-oxoguanine DNA glycosylase (OGG1), and
methylpurine DNA glycosylase (MPG), all of which repair oxidative DNA damage as
part of the base excision repair pathways. A blinded population-based case
control study was conducted with 96 patients with lung cancer and 96 control
subjects matched by gender, age (+/-1 year), place of residence, and ethnic group
(Jews/non-Jews). The three DNA repair activities were measured, and an integrated
DNA repair OMA (OGG1, MPG, and APE1) score was calculated for each individual.
Conditional logistic regression analysis revealed that individuals in the lowest
tertile of the integrated DNA repair OMA score had an increased risk of lung
cancer compared with the highest tertile, with OR = 9.7; 95% confidence interval
(CI), 3.1-29.8; P < 0.001, or OR = 5.6; 95% CI, 2.1-15.1; P < 0.001 after cross
validation. These results suggest that pending validation, this DNA repair panel
of risk factors may be useful for lung cancer risk assessment, assisting
prevention and referral to early detection by technologies such as low-dose
computed tomography scanning.
PMID- 24356340
TI - The role of physical activity in chronic kidney disease in the presence of
diabetes mellitus: a prospective cohort study.
AB - BACKGROUND/AIMS: Although the effect of exercise on health is well established,
nephrologists seldom consider physical activity in the treatment of chronic
kidney disease (CKD) or CKD in the presence of diabetes mellitus (DM/CKD). The
aim of the present study was to analyze the benefits of leisure-time physical
activity (LTPA) in DM/CKD. METHODS: A total of 445,075 adult participants who
underwent a medical screening program between 1996 and 2008 were prospectively
recruited. Of these, 7,863 DM/CKD subjects were identified. Each participant was
categorized according to LTPA level (a product of duration and intensity) as
inactive, low-active or fully active. Hazard ratios (HRs) for mortality risk were
calculated. RESULTS: Fully active LTPA was associated with lower odds of DM/CKD
development and lower risk of mortality among patients with DM/CKD in a dose
response relationship. The fully active and low-active DM/CKD groups had a 26%
(HR 0.74, 95% CI 0.66-0.85) and 13% (HR 0.87, 95% CI 0.75-1.01) lower risk of all
cause mortality, respectively, in comparison to the inactive group. The
association of exercise with mortality rate reduction was more pronounced among
DM/CKD subjects (mortality rate reduction of 446.5 per 100,000 person-years) than
among subjects with diabetes alone or CKD alone. CONCLUSION: Exercise, at the
recommended level or more, is associated not only with lower odds of DM/CKD but
also with a 26% lower mortality risk among DM/CKD patients. Nephrologists should
encourage all DM/CKD subjects to be physically active
PMID- 24356342
TI - Development of an ultra-thin film comprised of a graphene membrane and carbon
nanotube vein support.
AB - Graphene, exhibiting superior mechanical, thermal, optical and electronic
properties, has attracted great interest. Considering it being one-atom-thick,
and the reduced mechanical strength at grain boundaries, the fabrication of large
area suspended chemical vapour deposition graphene remains a challenge. Here we
report the fabrication of an ultra-thin free-standing carbon nanotube/graphene
hybrid film, inspired by the vein-membrane structure found in nature. Such a
square-centimetre-sized hybrid film can realize the overlaying of large-area
single-layer chemical vapour deposition graphene on to a porous vein-like carbon
nanotube network. The vein-membrane-like hybrid film, with graphene suspended on
the carbon nanotube meshes, possesses excellent mechanical performance, optical
transparency and good electrical conductivity. The ultra-thin hybrid film
features an electron transparency close to 90%, which makes it an ideal gate
electrode in vacuum electronics and a high-performance sample support in
transmission electron microscopy.
PMID- 24356341
TI - Combination of the clock drawing test with the physical phenotype of frailty for
the prediction of mortality and other adverse outcomes in older community
dwellers without dementia.
AB - BACKGROUND: Cognitive assessment is thought to increase the ability of the
physical phenotype of frailty to identify older persons at a higher risk for
adverse outcomes. OBJECTIVE: Data from a cohort of dementia-free community
dwellers were used to investigate whether the clock drawing test (CDT), a quick
and easy cognitive screening test, is associated with adverse health outcomes
independently of the physical phenotype of frailty. METHODS: This was a
prospective population-based cohort study of 766 dementia-free Italian community
dwellers aged 65 years or older. Baseline assessment included the physical
phenotype of frailty, 3 different CDT protocols [Sunderland, Shulman, and the
clock drawing interpretation scale (CDIS)], and several health confounders.
Hazard ratios (HR) and odds ratio (OR) along with their corresponding 95%
confidence intervals (CI) from models adjusted for frailty and sociodemographic
and health confounders were used to estimate the independent association of the
CDT with the 7-year risk of all-cause mortality and the 3-year risk of new and
worsening disability, hospitalization, and fractures. RESULTS: After adjustment
for confounders, the Sunderland CDT was significantly associated with all-cause
mortality independently of the physical phenotype of frailty (HR = 1.44, 95% CI
1.03-2.01, p = 0.031). However, compared to all nonfrail participants with a
normal Sunderland CDT, the HR was 1.57 (95% CI 1.09-2.26, p = 0.016) for those
with impairment on the Sunderland CDT only, 2.48 (95% CI 1.46-4.20, p = 0.001)
for those with frailty only, and 2.52 (95% CI 1.34-4.77, p = 0.004) for those
with both frailty and impairment on the Sunderland CDT. Mortality was unrelated
to the CDIS CDT (p = 0.359) and the Shulman CDT (p = 0.281). No statistically
significant relationship was found between nonlethal outcomes and any CDT
protocol, although trends were found for an association of both the Sunderland
CDT (p = 0.118) and the CDIS CDT with worsening disability (p = 0.154).
CONCLUSIONS: In older persons, depending on the scoring system, the CDT may
predict the mortality risk independently of the physical phenotype of frailty.
However, combining the two measurements does not improve their individual
prognostic abilities.
PMID- 24356343
TI - Socioeconomic factors and the risk for sarcoma.
AB - Sarcomas are a heterogeneous group of rare malignancies arising from mesenchymal
tissue. Although several occupational exposures have been evaluated in
association with sarcoma, little is known about the role of socioeconomic
indicators such as education. Socioeconomic status has been found to be
associated with risk of development of several types of cancers, primarily lung,
gastric, and cervical cancers. We conducted a hospital-based case-control study
to evaluate the association of socioeconomic level with the risk for sarcoma. A
total of 371 incident cases of sarcoma were matched in terms of age, sex, and
year of enrollment in the study with 742 cancer-free controls. Education and
income levels were evaluated as the indicators of socioeconomic status. Higher
education (college level) was associated with a significantly lower risk for
sarcoma [odds ratio (OR)=0.48, 95% confidence interval (CI)=0.29-0.80], even
after adjusting for important confounders. After stratifying by sex,
significantly lower risk for sarcoma was observed among men who had college level
education compared with men with a level of education of eighth grade or lower
(OR=0.38, 95% CI=0.19-0.74). A significant association between education and the
risk for sarcoma remained after stratifying by income (OR=0.49, 95% CI=0.28-0.86,
among the low income group). When analyzed as a composite exposure, individuals
with high education and high income status had significantly lower risk for
sarcoma compared with those with low income and low education status (OR=0.41,
95% CI=0.23-0.71). Thus, socioeconomic factors may play a significant role in
determining the risk for sarcoma and should be explored further to elucidate the
underlying factors that may explain these sociodemographic inequalities related
to sarcoma.
PMID- 24356344
TI - A physically-based approach to reflection separation: from physical modeling to
constrained optimization.
AB - We propose a physically-based approach to separate reflection using multiple
polarized images with a background scene captured behind glass. The input
consists of three polarized images, each captured from the same view point but
with a different polarizer angle separated by 45 degrees. The output is the high
quality separation of the reflection and background layers from each of the input
images. A main technical challenge for this problem is that the mixing
coefficient for the reflection and background layers depends on the angle of
incidence and the orientation of the plane of incidence, which are spatially
varying over the pixels of an image. Exploiting physical properties of
polarization for a double-surfaced glass medium, we propose a multiscale scheme
which automatically finds the optimal separation of the reflection and background
layers. Through experiments, we demonstrate that our approach can generate
superior results to those of previous methods.
PMID- 24356345
TI - Category-independent object proposals with diverse ranking.
AB - We propose a category-independent method to produce a bag of regions and rank
them, such that top-ranked regions are likely to be good segmentations of
different objects. Our key objectives are completeness and diversity: Every
object should have at least one good proposed region, and a diverse set should be
top-ranked. Our approach is to generate a set of segmentations by performing
graph cuts based on a seed region and a learned affinity function. Then, the
regions are ranked using structured learning based on various cues. Our
experiments on the Berkeley Segmentation Data Set and Pascal VOC 2011 demonstrate
our ability to find most objects within a small bag of proposed regions.
PMID- 24356346
TI - Covariate shift adaptation for discriminative 3D pose estimation.
AB - Discriminative, or (structured) prediction, methods have proved effective for
variety of problems in computer vision; a notable example is 3D monocular pose
estimation. All methods to date, however, relied on an assumption that training
(source) and test (target) data come from the same underlying joint distribution.
In many real cases, including standard data sets, this assumption is flawed. In
the presence of training set bias, the learning results in a biased model whose
performance degrades on the (target) test set. Under the assumption of covariate
shift, we propose an unsupervised domain adaptation approach to address this
problem. The approach takes the form of training instance reweighting, where the
weights are assigned based on the ratio of training and test marginals evaluated
at the samples. Learning with the resulting weighted training samples alleviates
the bias in the learned models. We show the efficacy of our approach by proposing
weighted variants of kernel regression (KR) and twin Gaussian processes (TGP). We
show that our weighted variants outperform their unweighted counterparts and
improve on the state-of-the-art performance in the public (HumanEva) data set.
PMID- 24356347
TI - Efficient space-time sampling with pixel-wise coded exposure for high-speed
imaging.
AB - Cameras face a fundamental trade-off between spatial and temporal resolution.
Digital still cameras can capture images with high spatial resolution, but most
high-speed video cameras have relatively low spatial resolution. It is hard to
overcome this trade-off without incurring a significant increase in hardware
costs. In this paper, we propose techniques for sampling, representing, and
reconstructing the space-time volume to overcome this trade-off. Our approach has
two important distinctions compared to previous works: 1) We achieve sparse
representation of videos by learning an overcomplete dictionary on video patches,
and 2) we adhere to practical hardware constraints on sampling schemes imposed by
architectures of current image sensors, which means that our sampling function
can be implemented on CMOS image sensors with modified control units in the
future. We evaluate components of our approach, sampling function and sparse
representation, by comparing them to several existing approaches. We also
implement a prototype imaging system with pixel-wise coded exposure control using
a liquid crystal on silicon device. System characteristics such as field of view
and modulation transfer function are evaluated for our imaging system. Both
simulations and experiments on a wide range of scenes show that our method can
effectively reconstruct a video from a single coded image while maintaining high
spatial resolution.
PMID- 24356348
TI - Half-quadratic-based iterative minimization for robust sparse representation.
AB - Robust sparse representation has shown significant potential in solving
challenging problems in computer vision such as biometrics and visual
surveillance. Although several robust sparse models have been proposed and
promising results have been obtained, they are either for error correction or for
error detection, and learning a general framework that systematically unifies
these two aspects and explores their relation is still an open problem. In this
paper, we develop a half-quadratic (HQ) framework to solve the robust sparse
representation problem. By defining different kinds of half-quadratic functions,
the proposed HQ framework is applicable to performing both error correction and
error detection. More specifically, by using the additive form of HQ, we propose
an l1-regularized error correction method by iteratively recovering corrupted
data from errors incurred by noises and outliers; by using the multiplicative
form of HQ, we propose an l1-regularized error detection method by learning from
uncorrupted data iteratively. We also show that the l1-regularization solved by
soft-thresholding function has a dual relationship to Huber M-estimator, which
theoretically guarantees the performance of robust sparse representation in terms
of M-estimation. Experiments on robust face recognition under severe occlusion
and corruption validate our framework and findings.
PMID- 24356349
TI - Hashing hyperplane queries to near points with applications to large-scale active
learning.
AB - We consider the problem of retrieving the database points nearest to a given
hyperplane query without exhaustively scanning the entire database. For this
problem, we propose two hashing-based solutions. Our first approach maps the data
to 2-bit binary keys that are locality sensitive for the angle between the
hyperplane normal and a database point. Our second approach embeds the data into
a vector space where the euclidean norm reflects the desired distance between the
original points and hyperplane query. Both use hashing to retrieve near points in
sublinear time. Our first method's preprocessing stage is more efficient, while
the second has stronger accuracy guarantees. We apply both to pool-based active
learning: Taking the current hyperplane classifier as a query, our algorithm
identifies those points (approximately) satisfying the well-known minimal
distance-to-hyperplane selection criterion. We empirically demonstrate our
methods' tradeoffs and show that they make it practical to perform active
selection with millions of unlabeled points.
PMID- 24356350
TI - Learning discriminant face descriptor.
AB - Local feature descriptor is an important module for face recognition and those
like Gabor and local binary patterns (LBP) have proven effective face
descriptors. Traditionally, the form of such local descriptors is predefined in a
handcrafted way. In this paper, we propose a method to learn a discriminant face
descriptor (DFD) in a data-driven way. The idea is to learn the most discriminant
local features that minimize the difference of the features between images of the
same person and maximize that between images from different people. In
particular, we propose to enhance the discriminative ability of face
representation in three aspects. First, the discriminant image filters are
learned. Second, the optimal neighborhood sampling strategy is soft determined.
Third, the dominant patterns are statistically constructed. Discriminative
learning is incorporated to extract effective and robust features. We further
apply the proposed method to the heterogeneous (cross-modality) face recognition
problem and learn DFD in a coupled way (coupled DFD or C-DFD) to reduce the gap
between features of heterogeneous face images to improve the performance of this
challenging problem. Extensive experiments on FERET, CAS-PEAL-R1, LFW, and HFB
face databases validate the effectiveness of the proposed DFD learning on both
homogeneous and heterogeneous face recognition problems. The DFD improves POEM
and LQP by about 4.5 percent on LFW database and the C-DFD enhances the
heterogeneous face recognition performance of LBP by over 25 percent.
PMID- 24356351
TI - Learning multimodal latent attributes.
AB - The rapid development of social media sharing has created a huge demand for
automatic media classification and annotation techniques. Attribute learning has
emerged as a promising paradigm for bridging the semantic gap and addressing data
sparsity via transferring attribute knowledge in object recognition and
relatively simple action classification. In this paper, we address the task of
attribute learning for understanding multimedia data with sparse and incomplete
labels. In particular, we focus on videos of social group activities, which are
particularly challenging and topical examples of this task because of their
multimodal content and complex and unstructured nature relative to the density of
annotations. To solve this problem, we 1) introduce a concept of semilatent
attribute space, expressing user-defined and latent attributes in a unified
framework, and 2) propose a novel scalable probabilistic topic model for learning
multimodal semilatent attributes, which dramatically reduces requirements for an
exhaustive accurate attribute ontology and expensive annotation effort. We show
that our framework is able to exploit latent attributes to outperform
contemporary approaches for addressing a variety of realistic multimedia sparse
data learning tasks including: multitask learning, learning with label noise, N
shot transfer learning, and importantly zero-shot learning.
PMID- 24356352
TI - Matching by tone mapping: photometric invariant template matching.
AB - A fast pattern matching scheme termed matching by tone mapping (MTM) is
introduced which allows matching under nonlinear tone mappings. We show that,
when tone mapping is approximated by a piecewise constant/linear function, a fast
computational scheme is possible requiring computational time similar to the fast
implementation of normalized cross correlation (NCC). In fact, the MTM measure
can be viewed as a generalization of the NCC for nonlinear mappings and actually
reduces to NCC when mappings are restricted to be linear. We empirically show
that the MTM is highly discriminative and robust to noise with comparable
performance capability to that of the well performing mutual information, but on
par with NCC in terms of computation time.
PMID- 24356353
TI - Neighborhood repulsed metric learning for kinship verification.
AB - Kinship verification from facial images is an interesting and challenging problem
in computer vision, and there are very limited attempts on tackle this problem in
the literature. In this paper, we propose a new neighborhood repulsed metric
learning (NRML) method for kinship verification. Motivated by the fact that
interclass samples (without a kinship relation) with higher similarity usually
lie in a neighborhood and are more easily misclassified than those with lower
similarity, we aim to learn a distance metric under which the intraclass samples
(with a kinship relation) are pulled as close as possible and interclass samples
lying in a neighborhood are repulsed and pushed away as far as possible,
simultaneously, such that more discriminative information can be exploited for
verification. To make better use of multiple feature descriptors to extract
complementary information, we further propose a multiview NRML (MNRML) method to
seek a common distance metric to perform multiple feature fusion to improve the
kinship verification performance. Experimental results are presented to
demonstrate the efficacy of our proposed methods. Finally, we also test human
ability in kinship verification from facial images and our experimental results
show that our methods are comparable to that of human observers.
PMID- 24356354
TI - On Bayesian adaptive video super resolution.
AB - Although multiframe super resolution has been extensively studied in past
decades, super resolving real-world video sequences still remains challenging. In
existing systems, either the motion models are oversimplified or important
factors such as blur kernel and noise level are assumed to be known. Such models
cannot capture the intrinsic characteristics that may differ from one sequence to
another. In this paper, we propose a Bayesian approach to adaptive video super
resolution via simultaneously estimating underlying motion, blur kernel, and
noise level while reconstructing the original high-resolution frames. As a
result, our system not only produces very promising super resolution results
outperforming the state of the art, but also adapts to a variety of noise levels
and blur kernels. To further analyze the effect of noise and blur kernel, we
perform a two-step analysis using the Cramer-Rao bounds. We study how blur kernel
and noise influence motion estimation with aliasing signals, how noise affects
super resolution with perfect motion, and finally how blur kernel and noise
influence super resolution with unknown motion. Our analysis results confirm
empirical observations, in particular that an intermediate size blur kernel
achieves the optimal image reconstruction results.
PMID- 24356355
TI - Scene-specific pedestrian detection for static video surveillance.
AB - The performance of a generic pedestrian detector may drop significantly when it
is applied to a specific scene due to the mismatch between the source training
set and samples from the target scene. We propose a new approach of automatically
transferring a generic pedestrian detector to a scene-specific detector in static
video surveillance without manually labeling samples from the target scene. The
proposed transfer learning framework consists of four steps. 1) Through exploring
the indegrees from target samples to source samples on a visual affinity graph,
the source samples are weighted to match the distribution of target samples. 2)
It explores a set of context cues to automatically select samples from the target
scene, predicts their labels, and computes confidence scores to guide transfer
learning. 3) The confidence scores propagate among target samples according to
their underlying visual structures. 4) Target samples with higher confidence
scores have larger influence on training scene-specific detectors. All these
considerations are formulated under a single objective function called confidence
encoded SVM, which avoids hard thresholding on confidence scores. During test,
only the appearance-based detector is used without context cues. The
effectiveness is demonstrated through experiments on two video surveillance data
sets. Compared with a generic detector, it improves the detection rates by 48 and
36 percent at one false positive per image (FPPI) on the two data sets,
respectively. The training process converges after one or two iterations on the
data sets in experiments.
PMID- 24356356
TI - Toward integrated scene text reading.
AB - The growth in digital camera usage combined with a worldly abundance of text has
translated to a rich new era for a classic problem of pattern recognition,
reading. While traditional document processing often faces challenges such as
unusual fonts, noise, and unconstrained lexicons, scene text reading amplifies
these challenges and introduces new ones such as motion blur, curved layouts,
perspective projection, and occlusion among others. Reading scene text is a
complex problem involving many details that must be handled effectively for
robust, accurate results. In this work, we describe and evaluate a reading system
that combines several pieces, using probabilistic methods for coarsely binarizing
a given text region, identifying baselines, and jointly performing word and
character segmentation during the recognition process. By using scene context to
recognize several words together in a line of text, our system gives state-of-the
art performance on three difficult benchmark data sets.
PMID- 24356357
TI - Trinary-projection trees for approximate nearest neighbor search.
AB - We address the problem of approximate nearest neighbor (ANN) search for visual
descriptor indexing. Most spatial partition trees, such as KD trees, VP trees,
and so on, follow the hierarchical binary space partitioning framework. The key
effort is to design different partition functions (hyperplane or hypersphere) to
divide the points so that 1) the data points can be well grouped to support
effective NN candidate location and 2) the partition functions can be quickly
evaluated to support efficient NN candidate location. We design a trinary
projection direction-based partition function. The trinary-projection direction
is defined as a combination of a few coordinate axes with the weights being 1 or
1. We pursue the projection direction using the widely adopted maximum variance
criterion to guarantee good space partitioning and find fewer coordinate axes to
guarantee efficient partition function evaluation. We present a coordinate-wise
enumeration algorithm to find the principal trinary-projection direction. In
addition, we provide an extension using multiple randomized trees for improved
performance. We justify our approach on large-scale local patch indexing and
similar image search.
PMID- 24356358
TI - Video event detection: from subvolume localization to spatiotemporal path search.
AB - Although sliding window-based approaches have been quite successful in detecting
objects in images, it is not a trivial problem to extend them to detecting events
in videos. We propose to search for spatiotemporal paths for video event
detection. This new formulation can accurately detect and locate video events in
cluttered and crowded scenes, and is robust to camera motions. It can also well
handle the scale, shape, and intraclass variations of the event. Compared to
event detection using spatiotemporal sliding windows, the spatiotemporal paths
correspond to the event trajectories in the video space, thus can better handle
events composed by moving objects. We prove that the proposed search algorithm
can achieve the global optimal solution with the lowest complexity. Experiments
are conducted on realistic video data sets with different event detection tasks,
such as anomaly event detection, walking person detection, and running detection.
Our proposed method is compatible with different types of video features or
object detectors and robust to false and missed local detections. It
significantly improves the overall detection and localization accuracy over the
state-of-the-art methods.
PMID- 24356360
TI - A whole surface approach to crowd simulation on arbitrary topologies.
AB - Recent crowd simulation algorithms do path planning on complex surfaces by
breaking 3D surfaces into a series of 2.5D planes. This allows for path planning
on surfaces that can be mapped from 3D to 2D without distortion, such as
multistory buildings. However, the 2.5D approach does not handle path planning on
curved surfaces such as spheres, asteroids, or insect colonies. Additionally, the
2.5D approach does not handle the complexity of dynamic obstacle avoidance when
agents can walk on walls or ceilings. We propose novel path planning and obstacle
avoidance algorithms that work on surfaces as a whole instead of breaking them
into a 2.5D series of planes. Our "whole surfacea approach simulates crowds on
both multistory structures and highly curved topologies without changing
parameters. We validate our work on a suite of 30 different meshes, some with
over 100,000 triangles, with crowds of 1,000 agents. Our algorithm always
averaged more than 40 FPS with virtually no stalling.
PMID- 24356359
TI - Use of a text message program to raise type 2 diabetes risk awareness and promote
health behavior change (part II): assessment of participants' perceptions on
efficacy.
AB - BACKGROUND: Although there is great enthusiasm in both the public and private
sector for the further development and use of large-scale consumer-facing public
health applications for mobile platforms, little is known about user experience
and satisfaction with this type of approach. As a part of the Beacon Community
Cooperative Agreement Program, txt4health, a public-facing, mobile phone-based
health information service targeting type 2 diabetes, was launched in 3 Beacon
Communities: the Southeast Michigan Beacon Community in Detroit, MI, the Greater
Cincinnati Beacon Community in Cincinnati, OH, and the Crescent City Beacon
Community in New Orleans, LA. This program was marketed via large public health
campaigns and drew many users within the respective communities. OBJECTIVE: The
purpose of this investigation was to use the RE-AIM framework to document
txt4health efficacy by focusing on perceptions of satisfaction, usage, and
behavior change among individuals who used txt4health in pilot studies in
Southeast Michigan and Greater Cincinnati. METHODS: We conducted a multimodal
user survey with txt4health users recruited via text message through the program
to understand participant perceptions of program use and satisfaction, as well as
self-reported perceptions of behavior change as a result of using txt4health.
RESULTS: Txt4health users reported very high levels of program satisfaction, with
67.1% (108/161) reporting satisfaction scores of >=8 on a 10-point scale, with 10
equivalent to most satisfied (mean 8.2, SD 1.6). All survey participants
agreed/strongly agreed that the messages included in txt4health were clear and
easy to understand (100.0%, 160/160), and most found txt4health made them
knowledgeable about their risk for type 2 diabetes (88.1%, 140/159) and made them
conscious of their diet and physical activity (88.8%, 142/160). Most participants
reported that txt4health helped them to make behavior changes related to diet;
after having completed txt4health, most agreed/strongly agreed that they are more
likely to replace sugary drinks, such as juice or soda, with water (78.0%,
124/159), have a piece of fresh fruit instead of dessert (74.2%, 118/159),
substitute a small salad for chips or fries when dining out (76.1%, 121/159), buy
healthier foods when grocery shopping (79.7%, 126/158), and eat more grilled,
baked, or broiled foods instead of fried (75.5%, 120/159). CONCLUSIONS: Results
from this study suggest that participants in txt4health, a large-scale, public
health-focused text message program targeting type 2 diabetes, have positive
perceptions of the program and that participation has led to positive behavior
change.
PMID- 24356361
TI - Affine arithmetic-based B-spline surface intersection with GPU acceleration.
AB - Because the B-spline surface intersection is a fundamental operation in geometric
design software, it is important to make the surface intersection operation
robust and efficient. As is well known, affine arithmetic is robust for
calculating the surface intersection because it is able to not only find every
branch of the intersection, but also deal with some singular cases, such as
surface tangency. However, the classical affine arithmetic is defined only for
the globally supported polynomials, and its computation is very time consuming,
thus hampering its usefulness in practical applications, especially in geometric
design. In this paper, we extend affine arithmetic to calculate the range of
recursively and locally defined B-spline basis functions, and we accelerate the
affine arithmetic-based surface intersection algorithm by using a GPU. Moreover,
we develop efficient methods to thin the strip-shaped intersection regions
produced by the affine arithmetic-based intersection algorithm, calculate the
intersection points, and further improve their accuracy. The many examples
presented in this paper demonstrate the robustness and efficiency of this method.
PMID- 24356362
TI - Content-aware photo collage using circle packing.
AB - In this paper, we present a novel approach for automatically creating the photo
collage that assembles the interest regions of a given group of images naturally.
Previous methods on photo collage are generally built upon a well-defined
optimization framework, which computes all the geometric parameters and layer
indices for input photos on the given canvas by optimizing a unified objective
function. The complex nonlinear form of optimization function limits their
scalability and efficiency. From the geometric point of view, we recast the
generation of collage as a region partition problem such that each image is
displayed in its corresponding region partitioned from the canvas. The core of
this is an efficient power-diagram-based circle packing algorithm that arranges a
series of circles assigned to input photos compactly in the given canvas. To
favor important photos, the circles are associated with image importances
determined by an image ranking process. A heuristic search process is developed
to ensure that salient information of each photo is displayed in the polygonal
area resulting from circle packing. With our new formulation, each factor
influencing the state of a photo is optimized in an independent stage, and
computation of the optimal states for neighboring photos are completely
decoupled. This improves the scalability of collage results and ensures their
diversity. We also devise a saliency-based image fusion scheme to generate
seamless compositive collage. Our approach can generate the collages on
nonrectangular canvases and supports interactive collage that allows the user to
refine collage results according to his/her personal preferences. We conduct
extensive experiments and show the superiority of our algorithm by comparing
against previous methods.
PMID- 24356363
TI - Feature-based analysis of plasma-based particle acceleration data.
AB - Plasma-based particle accelerators can produce and sustain thousands of times
stronger acceleration fields than conventional particle accelerators, providing a
potential solution to the problem of the growing size and cost of conventional
particle accelerators. To facilitate scientific knowledge discovery from the ever
growing collections of accelerator simulation data generated by accelerator
physicists to investigate next-generation plasma-based particle accelerator
designs, we describe a novel approach for automatic detection and classification
of particle beams and beam substructures due to temporal differences in the
acceleration process, here called acceleration features. The automatic feature
detection in combination with a novel visualization tool for fast, intuitive,
query-based exploration of acceleration features enables an effective top-down
data exploration process, starting from a high-level, feature-based view down to
the level of individual particles. We describe the application of our analysis in
practice to analyze simulations of single pulse and dual and triple colliding
pulse accelerator designs, and to study the formation and evolution of particle
beams, to compare substructures of a beam, and to investigate transverse particle
loss.
PMID- 24356364
TI - Interactive formation control in complex environments.
AB - The degrees of freedom of a crowd is much higher than that provided by a standard
user input device. Typically, crowd-control systems require multiple passes to
design crowd movements by specifying waypoints, and then defining character
trajectories and crowd formation. Such multi-pass control would spoil the
responsiveness and excitement of real-time control systems. In this paper, we
propose a single-pass algorithm to control a crowd in complex environments. We
observe that low-level details in crowd movement are related to interactions
between characters and the environment, such as diverging/merging at cross
points, or climbing over obstacles. Therefore, we simplify the problem by
representing the crowd with a deformable mesh, and allow the user, via multitouch
input, to specify high-level movements and formations that are important for
context delivery. To help prevent congestion, our system dynamically reassigns
characters in the formation by employing a mass transport solver to minimize
their overall movement. The solver uses a cost function to evaluate the impact
from the environment, including obstacles and areas affecting movement speed.
Experimental results show realistic crowd movement created with minimal high
level user inputs. Our algorithm is particularly useful for real-time
applications including strategy games and interactive animation creation.
PMID- 24356365
TI - Lattice cleaving: a multimaterial tetrahedral meshing algorithm with guarantees.
AB - We introduce a new algorithm for generating tetrahedral meshes that conform to
physical boundaries in volumetric domains consisting of multiple materials. The
proposed method allows for an arbitrary number of materials, produces high
quality tetrahedral meshes with upper and lower bounds on dihedral angles, and
guarantees geometric fidelity. Moreover, the method is combinatoric so its
implementation enables rapid mesh construction. These meshes are structured in a
way that also allows grading, to reduce element counts in regions of homogeneity.
Additionally, we provide proofs showing that both element quality and geometric
fidelity are bounded using this approach.
PMID- 24356366
TI - Memory-hazard-aware k-buffer algorithm for order-independent transparency
rendering.
AB - The (k)-buffer algorithm is an efficient GPU-based fragment level sorting
algorithm for rendering transparent surfaces. Because of the inherent massive
parallelism of GPU stream processors, this algorithm suffers serious read-after
write memory hazards now. In this paper, we introduce an improved (k)-buffer
algorithm with error correction coding to combat memory hazards. Our algorithm
results in significantly reduced artifacts. While preserving all the merits of
the original algorithm, it requires merely OpenGL 3.x support from the GPU,
instead of the atomic operations appearing only in the latest OpenGL 4.2
standard. Our algorithm is simple to implement and efficient in performance.
Future GPU support for improving this algorithm is also proposed.
PMID- 24356367
TI - Moving least-squares reconstruction of large models with GPUs.
AB - Modern laser range scanning campaigns produce extremely large point clouds, and
reconstructing a triangulated surface thus requires both out-of-core techniques
and significant computational power. We present a GPU-accelerated implementation
of the moving least-squares (MLS) surface reconstruction technique. We believe
this to be the first GPU-accelerated, out-of-core implementation of surface
reconstruction that is suitable for laser range-scanned data. While several
previous out-of-core approaches use a sweep-plane approach, we subdivide the
space into cubic regions that are processed independently. This independence
allows the algorithm to be parallelized using multiple GPUs, either in a single
machine or a cluster. It also allows data sets with billions of point samples to
be processed on a standard desktop PC. We show that our implementation is an
order of magnitude faster than a CPU-based implementation when using a single
GPU, and scales well to 8 GPUs.
PMID- 24356368
TI - Personal photograph enhancement using internet photo collections.
AB - Given the growth of Internet photo collections, we now have a visual index of all
major cities and tourist sites in the world. However, it is still a difficult
task to capture that perfect shot with your own camera when visiting these
places, especially when your camera itself has limitations, such as a limited
field of view. In this paper, we propose a framework to overcome the
imperfections of personal photographs of tourist sites using the rich information
provided by large-scale Internet photo collections. Our method deploys state-of
the-art techniques for constructing initial 3D models from photo collections. The
same techniques are then used to register personal photographs to these models,
allowing us to augment personal 2D images with 3D information. This strong
available scene prior allows us to address a number of traditionally challenging
image enhancement techniques and achieve high-quality results using simple and
robust algorithms. Specifically, we demonstrate automatic foreground
segmentation, mono-to-stereo conversion, field-of-view expansion, photometric
enhancement, and additionally automatic annotation with geolocation and tags. Our
method clearly demonstrates some possible benefits of employing the rich
information contained in online photo databases to efficiently enhance and
augment one's own personal photographs.
PMID- 24356369
TI - Surface and contour-preserving origamic architecture paper pop-ups.
AB - Origamic architecture (OA) is a form of papercraft that involves cutting and
folding a single sheet of paper to produce a 3D pop-up, and is commonly used to
depict architectural structures. Because of the strict geometric and physical
constraints, OA design requires considerable skill and effort. In this paper, we
present a method to automatically generate an OA design that closely depicts an
input 3D model. Our algorithm is guided by a novel set of geometric conditions to
guarantee the foldability and stability of the generated pop-ups. The generality
of the conditions allows our algorithm to generate valid pop-up structures that
are previously not accounted for by other algorithms. Our method takes a novel
image-domain approach to convert the input model to an OA design. It performs
surface segmentation of the input model in the image domain, and carefully
represents each surface with a set of parallel patches. Patches are then modified
to make the entire structure foldable and stable. Visual and quantitative
comparisons of results have shown our algorithm to be significantly better than
the existing methods in the preservation of contours, surfaces, and volume. The
designs have also been shown to more closely resemble those created by real
artists.
PMID- 24356370
TI - Turbulence simulation by adaptive multi-relaxation lattice boltzmann modeling.
AB - This paper presents a novel approach to simulating turbulent flows by developing
an adaptive multirelaxation scheme in the framework of lattice Boltzmann equation
(LBE). Existing LBE methods in graphics simulations are usually insufficient for
turbulent flows since the collision term disturbs the underlying stability and
accuracy. We adopt LBE with the multiple relaxation time (MRT) collision model
(MRT-LBE), and address this issue by enhancing the collision-term modeling.
First, we employ renormalization group analysis and formulate a new turbulence
model with an adaptive correction method to compute more appropriate eddy
viscosities on a uniform lattice structure. Efficient algebraic calculations are
retained with small-scale turbulence details while maintaining the system
stability. Second, we note that for MRT-LBE, predicting single eddy viscosity per
lattice node may still result in instability. Hence, we simultaneously predict
multiple eddy viscosities for stress-tensor-related elements, thereby
asynchronously computing multiple relaxation parameters to further enhance the
MRT-LBE stability. With these two new strategies, turbulent flows can be
simulated with finer visual details even on coarse grid configurations. We
demonstrate our results by simulating and visualizing various turbulent flows,
particularly with smoke animations, where stable turbulent flows with high
Reynolds numbers can be faithfully produced.
PMID- 24356371
TI - Vortical inviscid flows with two-way solid-fluid coupling.
AB - Vortex methods increasingly receive attention from the computer graphics
community for simple and direct modeling of complex flow phenomena such as
turbulence. The coupling between free-form solids, represented by arbitrary
surface meshes, and fluids simulated with vortex methods, leads to visually rich
simulations. In this paper, we introduce a novel approach for simulating the
interaction between solids and inviscid fluids for high-quality simulations using
Lagrangian vortex particles. The key aspect of our method is simulating the
creation of vorticity at a solid's surface. While previous vortex simulators only
focus on modeling the solid as a boundary for the fluid, our approach allows the
accurate simulation of two processes of visual interest. The first is the
introduction of surface vorticity in the main flow as turbulence (vortex
shedding). The second is the motion of the solid induced by fluid forces. We also
introduce to computer graphics the concept of source panels to model nonturbulent
flow around objects. To the best of our knowledge, this is the first work on two
way coupling of 3D solids and fluids using Lagrangian vortex methods in computer
graphics.
PMID- 24356372
TI - Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and
cytotoxicity by inhibiting p38MAPK/NFkappaB pathway in H9c2 cardiac cells.
AB - BACKGROUND/AIM: We have demonstrated that exogenous hydrogen sulfide (H2S)
protects H9c2 cardiac cells against the doxorubicin (DOX)-induced injuries by
inhibiting p38 mitogen-activated protein kinase (MAPK) pathway and that the p38
MAPK/nuclear factor-kappaB (NF-kappaB) pathway is involved in the DOX-induced
inflammatory response and cytotoxicity. The present study attempts to test the
hypothesis that exogenous H2S might protect cardiomyocytes against the DOX
induced inflammation and cytotoxicity through inhibiting p38 MAPK/NF-kappaB
pathway. METHODS: H9c2 cardiac cells were exposed to 5MUM DOX for 24 h to
establish a model of DOX cardiotoxicity. The cells were pretreated with NaHS( a
donor of H2S) or other drugs before exposure to DOX. Cell viability was analyzed
by cell counter kit 8 ( CCK-8), The expression of NF-kappaB p65 and inducible
nitric oxide synthase (iNOS) was detected by Western blot assay. The levels of
interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha)
were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings
demonstrated that pretreatment of H9c2 cardiac cells with NaHS for 30 min before
exposure to DOX markedly ameliorated the DOX-induced phosphorylation and nuclear
translocation of NF-kappaB p65 subunit. Importantly, the pretreatment with NaHS
significantly attenuated the p38 MAPK/NF-kappaB pathway-mediated inflammatory
responses induced by DOX, as evidenced by decreases in the levels of IL-1beta, IL
6 and TNF-alpha. In addition, application of NaHS or IL-1beta receptor antagonist
(IL-1Ra) or PDTC (an inhibitor of NF-kappaB) attenuated the DOX-induced
expression of iNOS and production of nitric oxide (NO), respectively.
Furthermore, IL-1Ra also dramatically reduced the DOX-induced cytotoxicity and
phosphorylation of NF-kappaB p65. The pretreatment of H9c2 cells with N-acetyl-L
cysteine (NAC), a scavenger of reactive oxygen species (ROS) prior to exposure to
DOX depressed the phosphorylation of NF-kappaB p65 induced by DOX. CONCLUSION:
The present study has demonstrated the new mechanistic evidence that exogenous
H2S attenuates the DOX-induced inflammation and cytotoxicity by inhibiting p38
MAPK/NF-kappaB pathway in H9c2 cardiac cells. We also provide novel data that the
interaction between NF-kappaB pathway and IL-1beta is important in the induction
of DOX-induced inflammation and cytotoxicity in H9c2 cardiac cells.
PMID- 24356373
TI - Recent advances in solution-processed inorganic nanofilm photodetectors.
AB - As important opto-electronical devices, nanofilm photodetectors constructed from
inorganic low-dimensional nanostructures have drawn prime attention due to their
significance in basic scientific research and potential technological
applications. This review highlights a selection of important topics pertinent to
inorganic nanofilm photodetectors processed via solution strategies. This article
begins with a description of the advantages and drawbacks of nanofilm-based
photodetectors versus 1D nanostructure-based ones, and then introduces rational
design and controlled syntheses of various nanofilms via different wet-chemical
routes, and then mainly focuses on their optoelectronic properties and
applications in photodetectors based on the different types of nanofilms.
Finally, the general challenges and the potential future directions of this
exciting research and technology area are presented.
PMID- 24356374
TI - A FIB induced boiling mechanism for rapid nanopore formation.
AB - Focused ion beam (FIB) technology is widely used to fabricate nanopores in solid
state membranes. These nanopores have desirable thermomechanical properties for
applications such as high-throughput DNA sequencing. Using large scale molecular
dynamics simulations of the FIB nanopore formation process, we show that there is
a threshold ion delivery rate above which the mechanism underlying nanopore
formation changes. At low rates nanopore formation is slow, with the rate
proportional to the ion flux and therefore limited by the sputter rate of the
target material. However, at higher fluxes nanopores form via a thermally
dominated process, consistent with an explosive boiling mechanism. In this case,
mass is rapidly rearranged via bubble growth and coalescence, much more quickly
than would occur during sputtering. This mechanism has the potential to greatly
speed up nanopore formation.
PMID- 24356375
TI - The relative dose response test based on retinol-binding protein 4 is not
suitable to assess vitamin A status in very low birth weight infants.
AB - BACKGROUND: The relative dose response (RDR) test, which quantifies the increase
in serum retinol after vitamin A administration, is a qualitative measure of
liver vitamin A stores. Particularly in preterm infants, the feasibility of the
RDR test involving blood is critically dependent on small sample volumes.
OBJECTIVES: This study aimed to assess whether the RDR calculated with retinol
binding protein 4 (RBP4) might be a substitute for the classical retinol-based
RDR test for assessing vitamin A status in very preterm infants. METHODS: This
study included preterm infants with a birth weight below 1,500 g (n = 63, median
birth weight 985 g, median gestational age 27.4 weeks) who were treated with
5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3
(first vitamin A injection) and day 28 of life (last vitamin A injection), the
RDR was calculated and compared using serum retinol and RBP4 concentrations.
RESULTS: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased
significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was
27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5%
(-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR
and RBP4-RDR revealed no significant correlation. The agreement between retinol
RDR and RBP4-RDR was poor (day 3: Cohen's kappa = 0.12; day 28: Cohen's kappa =
0.18). CONCLUSION: The RDR test based on circulating RBP4 is unlikely to reflect
the hepatic vitamin A status in preterm infants.
PMID- 24356376
TI - Interaction between MAOA and FOXP2 in association with autism and verbal
communication in a Korean population.
AB - Expression levels of monoamine oxidase A (MAOA), the enzyme that related to
monoamine neurotransmitters metabolism such as serotonin, are related to
schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a
transcription factor, is associated with abnormal language development and is
expressed in several areas of the central nervous system in response to
serotonin. For this reason, we undertook interaction analysis between MAOA and
FOXP2 in autism spectrum disorder, including testing the verbal communication
score of the childhood autism rating scale. In interaction analysis, the FOXP2
TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323
rs1801291-rs3027407) haplotype were significantly associated with autism spectrum
disorder in males. However, when the interaction term was omitted, neither MAOA
nor FOXP2 was associated with autism spectrum disorder or verbal communication.
These results indicate that language and speech ability is affected by an
interaction between FOXP2 and MAOA, but not by either gene separately.
PMID- 24356378
TI - Gap junction signalling is a stress-regulated component of adrenal neuroendocrine
stimulus-secretion coupling in vivo.
AB - Elucidating the mechanisms whereby neuroendocrine tissues coordinate their input
and output signals to ensure appropriate hormone secretion is currently a topical
issue. In particular, whether a direct communication mediated by gap junctions
between neurosecretory cells contributes to hormone release in vivo still remains
unknown. Here we address this issue using a microsurgical approach allowing
combined monitoring of adrenal catecholamine secretion and splanchnic nerve
stimulation in anaesthetised mice. Pharmacological blockade of adrenal gap
junctions by the uncoupling agent carbenoxolone reduces nerve stimulation-evoked
catecholamine release in control mice and to a larger extent in stressed mice. In
parallel, the gap junction-coupled cell network is extended in stressed mice.
Altogether, this argues for a significant contribution of adrenomedullary gap
junctions to catecholamine secretion in vivo. As such, gap junctional signalling
appears to be a substantial component for neuroendocrine function in the adrenal
medulla, as it may represent an additional lever regulating hormone release.
PMID- 24356379
TI - Should omentectomy be a part of surgical staging in patients with endometrioid
adenocarcinoma of the uterine corpus?
AB - BACKGROUND: The purpose of the study was to determine the prevalence of omental
metastasis in endometrioid adenocarcinoma and to correlate risk variables with
this spread. METHODS: A retrospective analysis of patients with endometrioid
adenocarcinoma who underwent omentectomy in addition to staging laparotomy was
performed. RESULTS: Omental metastases were noted in 11 of the 322 patients with
endometrioid adenocarcinoma (3.4%). Multivariate analyses showed that there was a
significant correlation between omental metastasis and positive peritoneal
cytology, adnexal involvement, and grade 3 tumor (p = 0.028, p = 0.001, and p =
0.01, respectively). There was no statistical relationship between omental
metastasis and lymphovascular space involvement, deep myometrial invasion, and
lymph node metastasis (p = 0.087, p = 0.97, and p = 0.92, respectively).
CONCLUSION: Grade 3 endometrioid adenocarcinomas, especially those that are
complicated by deep myometrial invasion, have a pattern of intra-abdominal spread
similar to more aggressive endometrial cancers, with frequent involvement of the
omentum. Overall, we conclude that 37.5% (3/8) of patients who had a grade 3
tumor and omental metastasis stage IV disease would have been missed if a staging
operation similar to that employed for ovarian cancer had not been performed.
PMID- 24356377
TI - Heart rate variability is a predictor of mortality in chronic kidney disease: a
report from the CRIC Study.
AB - BACKGROUND/AIMS: Low heart rate variability (HRV) is a risk factor for adverse
outcomes in the general population. We aimed to determine the factors associated
with HRV and evaluate the association between low HRV and clinical outcomes in
patients with chronic kidney disease (CKD). METHODS: A 10-second
electrocardiogram was obtained at baseline in the Chronic Renal Insufficiency
Cohort (CRIC) Study. HRV was measured by the standard deviation of all R-R
intervals (SDNN) and the root mean square of successive differences between R-R
intervals (RMSSD). RESULTS: In 3,245 CRIC participants with available baseline
SDNN and RMSSD, lower HRV was associated with older age, lack of exercise, heart
failure, elevated phosphorus and hemoglobin A1c, and low estimated glomerular
filtration rate. After a median follow-up of 4.2 years, in fully adjusted models,
lower HRV was not associated with renal [SDNN: hazard rate, HR = 0.96 (95%
confidence interval, CI 0.88-1.05); RMSSD: HR = 0.97 (95% CI 0.88-1.07)] or
cardiovascular outcomes [SDNN: HR = 1.02 (95% CI 0.92-1.13); RMSSD: HR = 1.00
(95% CI 0.90-1.10)]. There was a nonlinear relationship between RMSSD and all
cause mortality with increased risk with both low and high RMSSD (p = 0.04).
CONCLUSIONS: In a large cohort of patients with CKD, multiple risk factors for
renal and cardiovascular diseases were associated with lower HRV. Lower HRV was
not associated with increased risk for renal or cardiovascular outcomes, but both
low and high RMSSD were associated with increased risk for all-cause mortality.
In conclusion, HRV measured by RMSSD may be a novel and independent risk factor
for mortality in CKD patients.
PMID- 24356380
TI - Editorial.
PMID- 24356382
TI - Frameless stereotactic functional neuronavigation combined with intraoperative
magnetic resonance imaging as a strategy in highly eloquent located tumors
causing epilepsy.
AB - BACKGROUND: Intractable epilepsy due to tumors located in highly eloquent brain
regions is often considered surgically inaccessible because of a high risk of
postoperative neurological deterioration. Intraoperative MRI and functional
navigation contribute to overcome this problem. OBJECTIVES: To retrospectively
investigate the long-term results and impact of functional neuronavigation and
1.5-tesla intraoperative MRI on patients who underwent surgery of tumors
associated with epilepsy located close to or within eloquent brain areas.
METHODS: Nineteen patients (9 female, 10 male, mean age 41.4 +/- 13.4 years, 11
low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD
imaging, diffusion-tensor imaging tractography and magnetoencephalography.
Functional data were implemented into neuronavigation in this multimodal
approach. RESULTS: In 14 of 19 patients (74%), complete resection was achieved,
and in 5 patients significant tumor volume reduction was accomplished. Eight of
14 (57%) complete resections were achieved only by performing an intraoperative
image update. Neurological deterioration was found permanently in 2 patients.
After a mean follow-up of 43.8 +/- 23.8 months, 15 patients (79%) became seizure
free (Engel class Ia). CONCLUSIONS: Despite the highly eloquent location of
tumors causing intractable epilepsy, our multimodal approach led to complete
resection in more than two-thirds of patients with an acceptable neurological
morbidity and excellent long-term seizure control.
PMID- 24356381
TI - Computational assay of H7N9 influenza neuraminidase reveals R292K mutation
reduces drug binding affinity.
AB - The emergence of a novel H7N9 avian influenza that infects humans is a serious
cause for concern. Of the genome sequences of H7N9 neuraminidase available, one
contains a substitution of arginine to lysine at position 292, suggesting a
potential for reduced drug binding efficacy. We have performed molecular dynamics
simulations of oseltamivir, zanamivir and peramivir bound to H7N9, H7N9-R292K,
and a structurally related H11N9 neuraminidase. They show that H7N9 neuraminidase
is structurally homologous to H11N9, binding the drugs in identical modes. The
simulations reveal that the R292K mutation disrupts drug binding in H7N9 in a
comparable manner to that observed experimentally for H11N9-R292K. Absolute
binding free energy calculations with the WaterSwap method confirm a reduction in
binding affinity. This indicates that the efficacy of antiviral drugs against
H7N9-R292K will be reduced. Simulations can assist in predicting disruption of
binding caused by mutations in neuraminidase, thereby providing a computational
'assay.'
PMID- 24356383
TI - Prenatal diagnosis and management of monozygotic twins discordant for turner
syndrome.
AB - Discordance for Turner syndrome in monozygotic (MZ) twins, which is known as
heterokaryotypia, is very rare in MZ pregnancies. The combined effect of
idiochromosome loss due to an anaphase lag and the relocation of discordant
blastomeres may trigger the twinning procedure and discordance of Turner
syndrome. We present 2 cases of MZ twins discordant for Turner syndrome that were
diagnosed prenatally by ultrasound and cytogenetic studies (one fetus was 45,X
and the other 46,XX). Both cases, which involved monochorionic (MC) diamniotic
twins, underwent selective feticide and had favorable outcomes for the remaining
twin. Ultrasound, amniocentesis of both sacs (dual amniocentesis) and zygosity
determination are indispensable in diagnosing heterokaryotypia. Selective
feticide is a treatment option in cases of heterokaryotypic MC diamniotic twins,
and in our cases, it resulted in favorable outcomes for the remaining twin.
PMID- 24356384
TI - Graphyne as the membrane for water desalination.
AB - Permeation through membrane with pores is important in the choice of materials
for filtration and separation techniques. Here, we report by the molecular
dynamics simulations that a single-layer graphyne membrane can be impermeable to
salt ions, while it allows the permeation of water molecules. The salt rejection
and water permeability of graphyne are closely related to the hydrostatic
pressure, type of graphyne membrane, and the salt concentration of solution,
respectively. By analyzing hydration shell structure, we found that the average
coordination number of ions plays a key role in water purification. Our
calculation showed that the salt rejection of the graphyne-3 membrane is the best
and it can keep an ideal rate of 100% in consideration cases. In comprehensive
evaluation of both salt rejection and permeability, the graphyne-4 is a perfect
purification membrane. To sum up, our results indicated that the graphynes
(graphyne-3 and -4) not only have higher salt rejection but also possess higher
water permeability which is several orders of magnitude higher than conventional
reverse osmosis membranes. The single-layer graphyne membrane may have a great
potential application as a membrane for water purification.
PMID- 24356385
TI - Targeting interleukins for the treatment of inflammatory bowel disease-what lies
beyond anti-TNF therapy?
AB - : Inflammatory bowel disease accounts for significant patient morbidity in the
Western world. Several immunosuppressive therapies are available but are
associated with potential significant adverse effects. In addition, there remains
a cohort of patients with refractory or relapsing disease. Therefore, the search
for novel therapeutic agents continues. In this review, we evaluate the role of a
number of designated cytokines that are candidates in the pathogenesis of
inflammatory bowel disease and discuss how their manipulation has been explored
as a therapeutic strategy for this disease. The interleukins (ILs) chosen for
discussion reflect those that currently show most promise as future therapeutic
targets, as well as discussing the role of some of the most recently identified
ILs, such as IL-27, IL-33, IL-35, and IL-22, in this context.
PMID- 24356386
TI - Interaction of oxovanadium(IV)-salphen complexes with bovine serum albumin and
their cytotoxicity against cancer.
AB - Vanadyl compounds of clinical significance are recommended as drugs against
diseases such as tuberculosis, diabetes, cancer, etc. In order to check the
potential of the salphen ligands and oxovanadium(IV)-salphen complexes as drugs
their binding with bovine serum albumin (BSA) is investigated. The binding
constants measured at pH 7.4 using UV-vis absorption and fluorescence techniques
are in the range of 10(3)-10(5) M(-1). The quenching of the fluorescence of BSA
and appearance of enhanced luminescence of the salphen ligand/vanadium(IV)
complex at the increased [quencher] show efficient FRET from the protein to the
quencher and the distance of energy transfer estimated using Forster's theory is
in the range of 1.4-3.5 nm. Molecular docking studies (DFT) utilizing
oxovanadium(IV)-salphen derivatives show strong binding with BSA and give insight
into the binding modes, interaction pattern and stability of synthesized
complexes in the target site. The cytotoxicity study shows the ability of these
V(IV) complexes to inhibit the growth of AGS gastric cell lines.
PMID- 24356387
TI - Influence of bio-coatings on the recording performance of neural electrodes.
AB - Neural probes are complex devices consisting of metallic (often Pt based)
electrodes, spread over an insolating/dielectric backbone. Their functionality is
often limited in time because of the formation of scaring tissues around the
implantation tracks. Functionalization of the probes surface can be used to limit
the glial scar reaction. This is however challenging, as this treatment has to be
equally efficient on all probe surfaces (metallic as well as dielectric) and
should not influence the electrodes performances. This paper presents a novel
technique to functionalize recording neural probes with hyaluronic acid (HyA), a
major component of the extracellular matrix (ECM). HyA and the probe surface are
both modified to make the reaction feasible: HyA is chemically functionalized
with SS-pyridine groups while the probe surfaces are silanized. The thiol groups
thus introduced on the probe surface can then react with the HyA SS-pyridine
group, resulting in a covalent bonding of the latter on the former. The
electrodes are protected by introducing a pretreatment step, namely an additional
hyaluronic acid layer on the platinum electrode, prior to the silanization
process, which was found to be effective in reducing electrode impedance under
optimized conditions.
PMID- 24356389
TI - Associations between sleep disturbance and suicidal ideation in adolescents
admitted to an inpatient psychiatric unit.
AB - The goals of our study were to: 1) describe the incidence of disturbances in
sleep quality, sleep hygiene, sleep-related cognitions and nightmares; and 2)
investigate the association between these sleep-related disturbances and suicidal
ideation (SI), in adolescents admitted to a psychiatric inpatient unit. Our
sample consisted of 50 adolescents between the ages of 12 and 17 years (32
females and 18 males; 41 Caucasian and nine African American). Our cross
sectional design involved the administration of the Adolescent Sleep Wake Scale
(ASWS), the Adolescent Sleep Hygiene Scale (ASHS), the Dysfunctional Beliefs and
Attitudes about Sleep-Short version for use with children (DBAS-C10), the
Disturbing Dreams and Nightmare Scale (DDNSI), and the Suicidal Ideation
Questionnaire Jr (SIQ-JR). Analyses were conducted using Pearson correlations, as
well as univariate and multivariate regression. Results indicated that our sample
experienced sleep disturbances and SI to a greater degree than non-clinical
samples. Sleep quality was correlated with nightmares, while sleep quality and
nightmares were each correlated with SI. Sleep quality, dysfunctional beliefs,
and nightmares each independently predicted SI. Our study was the first to use
the four sleep measures with an adolescent psychiatric inpatient sample. It is
important to develop sleep-related assessment tools in high-risk populations
given the link between sleep disturbances and suicidality. Furthermore, a better
understanding of the relationships between SI and sleep quality, sleep-related
cognitions, and nightmares is needed to develop potential prevention and
treatment options for suicidality in adolescents.
PMID- 24356390
TI - Absence of WNT4 gene mutation in a patient with MURCS association.
AB - MURCS (Mullerian duct aplasia, Renal anomalies, and Cervicothoracic Somite
dysplasia) association is a group of congenital genito-urinary and skeletal
malformations. We report an adolescent girl with the cardinal features of MURCS
association, obesity, and clinical findings of hyperandrogenism who did not show
any exonic mutation of the WNT4 gene. Our finding excludes WNT4 gene as a
candidate for MURCS association and suggests the need for further genetic
studies.
PMID- 24356388
TI - Cervical strain determined by ultrasound elastography and its association with
spontaneous preterm delivery.
AB - OBJECTIVE: To determine if there is an association between cervical strain,
evaluated using ultrasound elastography, and spontaneous preterm delivery (sPTD)
<37 weeks of gestation. METHODS: One hundred and eighty nine (189) women at 16-24
weeks of gestation were evaluated. Ultrasound elastography was used to estimate
cervical strain in three anatomical planes: one mid-sagittal in the same plane
used for cervical length measurement, and two cross sectional images: one at the
level of the internal cervical os, and the other at the level of the external
cervical os. In each plane, two regions of interest (endocervix and entire
cervix) were examined; a total of six regions of interest were evaluated.
RESULTS: The prevalence of sPTD was 11% (21/189). Strain values from each of the
six cervical regions correlated weakly with cervical length (from r=-0.24,
P<0.001 to r=-0.03, P=0.69). Strain measurements obtained in a cross sectional
view of the internal cervical os were significantly associated with sPTD. Women
with strain values <=25th centile in the endocervical canal (0.19) and in the
entire cervix (0.14) were 80% less likely to have a sPTD than women with strain
values >25th centile [endocervical: odds ratio (OR) 0.2; 95% confidence interval
(CI), 0.03-0.96; entire cervix: OR 0.17; 95% CI, 0.03-0.9]. Additional adjustment
for gestational age, race, smoking status, parity, maternal age, pre-pregnancy
body mass index, and previous preterm delivery did not appreciably alter the
magnitude or statistical significance of these associations. Strain values
obtained from the external cervical os and from the sagittal view were not
associated with sPTD. CONCLUSION: Low strain values in the internal cervical os
were associated with a significantly lower risk of spontaneous preterm delivery
<37 weeks of gestation.
PMID- 24356391
TI - Antipsychotic property of solvent-partitioned fractions of Lonchocarpus
cyanescens leaf extract in mice.
AB - BACKGROUND: This study was carried out to evaluate the antipsychotic property of
solvent-partitioned fractions of the leaf extract of Lonchocarpus cyanescens
(LC), a reputable medicinal plant used in folk medicine for the treatment of
mental illnesses in Nigeria. METHODS: The n-hexane fraction, ethyl acetate
fraction (EAF), and aqueous ethanol fraction (AEF) of LC were tested for
antipsychotic property based on the antagonism of stereotypy induced by
apomorphine (APO). Antagonism of hyperactivity and lethality in aggregated mice
induced by amphetamine (AMPH) were further employed for screening the
antipsychotic effect of the fractions. EAF was tested for catalepsy utilising the
horizontal plane paradigm. Thin-layer chromatography (TLC) was used to screen EAF
for the presence of secondary metabolites. RESULTS: AEF (100-400 mg/kg)
significantly (p<0.05) suppressed stereotypy induced by APO (2 mg/kg,
intraperitoneal [IP]) in comparison with control, suggesting antipsychotic
activity. However, EAF (200 mg/kg, IP) was most potent in inhibiting the
stereotypic effect of APO. EAF was also the most active in antagonising AMPH
induced hyperactivity and in protecting against death caused by AMPH in grouped
mice. However, in contrast to haloperidol, EAF did not produce cataleptic
behaviour in the horizontal plane paradigm. The TLC analysis revealed that EAF
contains several compounds, with some of them having Rf values similar to that of
haloperidol, which suggests the presence of active substances with the same
chemical structural identity. CONCLUSIONS: These findings suggest that EAF
contains the major active constituent(s) mediating the antipsychotic property of
LC and further support its use for the management of psychosis in traditional
medicine.
PMID- 24356392
TI - Underestimation of platelet count on magnesium salt-anticoagulated samples.
PMID- 24356393
TI - Rapid effects of Kikyo-to on sore throat pain associated with acute upper
respiratory tract infection.
AB - BACKGROUND: Kikyo-to is used empirically for relieving sore throat pain
associated with acute upper respiratory tract infection (URTI) in Japan. However,
few studies have demonstrated its clinical effect. This study was conducted to
investigate the efficacy of Kikyo-to on sore throat pain associated with acute
URTI. METHODS: Patients with sore throat pain who were diagnosed with URTI in
General Medicine Department Office, Tsukuba Medical Center Hospital from January
to March 2012 were enrolled. Patients received 2.5 g of Kikyo-to diluted in a cup
of hot water. The primary outcome was the change in sore throat score on the
visual analog scale (VAS) 10 min after Kikyo-to administration. Secondary
outcomes were change in sore throat score on VAS after 30 min and impact of sore
throat pain on daily life (none, mild, moderate, and severe) after 10 and 30 min.
RESULTS: Forty patients were eligible. Mean VAS score was 48.2+/-18.2 before
treatment and reduced significantly to 35.4+/-18.1 after 10 min and 30.7+/-19.3
after 30 min (p<0.001 in both periods). The proportion of patients with moderate
or more impact of sore throat pain on daily life was 67.5% and was reduced
significantly to 37.5% after 10 min and 30% after 30 min (p<0.001 in both
periods). The patients reported no side effects. CONCLUSIONS: Kikyo-to relieves
sore throat pain associated with acute URTI.
PMID- 24356394
TI - Specific management of anemia and hypertension in renal transplant recipients:
influence of renin-angiotensin system blockade.
AB - BACKGROUND: Renin-angiotensin system (RAS) inhibition has proven to be helpful in
reducing cardiovascular and kidney disease progression in the general population;
whether kidney transplant patients would derive similar benefits is unknown. RAS
inhibition also reduces posttransplantation erythrocytosis in kidney transplant
recipients, but its effect on hemoglobin (Hb) levels in patients without
posttransplantation erythrocytosis is unclear. METHODS: The Specific Management
of Anemia and Hypertension in Renal Transplant (SMAhRT) recipients study was
designed to examine the cardiovascular benefits of RAS blockade with telmisartan
80 mg versus placebo, and Hb management with darbepoetin alpha in a randomized,
double-blind, single-center controlled trial in 2,000 patients over 3 years. The
primary efficacy variable was a composite of all-cause mortality, myocardial
infarction or stroke. RESULTS: The SMAhRT study was stopped prematurely due to a
lower than expected event rate. At that point, 136 patients were enrolled and
were followed for a mean duration of 15 months. The use of RAS blockade was not
associated with an increased risk of adverse events such as worsening anemia or
hyperkalemia. Likewise, the correction of Hb with darbepoetin was not associated
with any increase in thrombotic events. CONCLUSIONS: This study provides insight
into the safety of RAS inhibition and Hb correction with an erythrocyte
stimulating agent in kidney transplant recipients.
PMID- 24356395
TI - 11 nm hard X-ray focus from a large-aperture multilayer Laue lens.
AB - The focusing performance of a multilayer Laue lens (MLL) with 43.4 MUm aperture,
4 nm finest zone width and 4.2 mm focal length at 12 keV was characterized with X
rays using ptychography method. The reconstructed probe shows a full-width-at
half-maximum (FWHM) peak size of 11.2 nm. The obtained X-ray wavefront shows
excellent agreement with the dynamical calculations, exhibiting aberrations less
than 0.3 wave period, which ensures the MLL capable of producing a diffraction
limited focus while offering a sufficient working distance. This achievement
opens up opportunities of incorporating a variety of in-situ experiments into
ultra high-resolution X-ray microscopy studies.
PMID- 24356396
TI - Human mesenchymal stem cells promote cancer motility and cytokine secretion in
vitro.
AB - Interactions of human mesenchymal stem cells (hMSC) with tumors are
controversially discussed since there is evidence for both tumor progression as
well as tumor inhibition by hMSC. The objective of the present study is to
investigate whether hMSC support cell motility and cytokine secretion in a head
and neck squamous cell carcinoma cell line (HLaC 78). A spheroid model was
generated in which the ultrastructure of spheroids was analyzed using scanning
electron microscopy (SEM). The migration capability was monitored in a monolayer
as well as in a spheroid model. The variation in migration and secretion of
interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF), as well
as the expression of the multidrug resistance gene (MDR-1) was investigated.
Finally, the alteration in the cell cycle was analyzed by flow cytometry. SEM
showed a tight cell-cell contact with extensive secretion of extracellular
matrix. The migration and invasion capability of HLaC 78 was enhanced by hMSC.
Cancer cell motility was also increased by hMSC as well as secretion of the
cytokines IL-6, IL-8 and VEGF. hMSC did not induce the expression of MDR-1 in
HLaC 78, and there was no alteration in the cell cycle of HLaC 78 after
cocultivation with hMSC. Our results confirm the important role of hMSC in cancer
biology since both an enhancement of cell motility as well as cytokine secretion
could be shown. However, based on these findings and those in the current
literature, caution must be applied when using hMSC as a carrier for tumor
therapy in cancer treatment.
PMID- 24356397
TI - Exogenous nerve growth factor promotes the repair of cardiac sympathetic
heterogeneity and electrophysiological instability in diabetic rats.
AB - OBJECTIVES: Diabetic cardiac autonomic neuropathy can lead to an increased
incidence of ventricular arrhythmias (VAs). However, few data are available
regarding the pathogenesis and therapy of the VAs accompanying diabetic cardiac
autonomic neuropathy. We aimed to explore whether or not exogenous nerve growth
factor (NGF) can reduce the sympathetic heterogeneity and the incidence of VAs in
diabetes mellitus (DM). METHODS: Male Wistar rats were randomly divided into 3
groups: controls, rats with DM with saline infused into the left stellate
ganglion (LSG), i.e. the DS group and rats with DM with NGF infused into the LSG,
i.e. the DN group. After 28 weeks, all rats were subjected to
electrophysiological experiments. Sympathetic innervations and NGF were studied
by immunostaining, RT-PCR or Western blot analysis. RESULTS: The incidence of
inducible VAs was significantly higher in the DS group than in the control group,
but was markedly decreased in the DN group. In the DS group, the tyrosine
hydroxylase (TH) and NGF expression were significantly lower than in the other
groups, and significant proximal-distal heterogeneities existed regarding the TH
and NGF expression in the left ventricle, but were markedly repaired in the DN
group. CONCLUSIONS: NGF intervention in the LSG can reduce the heterogeneity of
cardiac sympathetic innervations and the incidence of VAs in diabetic rats.
PMID- 24356398
TI - Effect of periodontal treatment in renal transplant recipients.
AB - OBJECTIVE: To evaluate the effect of periodontal treatment on gingival overgrowth
in a group of renal transplant patients. SUBJECTS AND METHODS: Twenty-five renal
transplant recipients receiving immunosuppressive therapy with cyclosporine A
(CsA) were randomly assigned to 2 groups. Group 1 (n = 15) included patients who
had been specifically referred to a dental clinic to prevent gingival overgrowth
and were given full periodontal therapy. Group 2 (n = 10) was comprised of
patients who did not receive any professional periodontal cleaning. Patients from
both groups were examined to determine their periodontal status before and after
3, 6 and 12 months in terms of their plaque index, gingival index and gingival
overgrowth. During the examination, their overall health was stable. RESULTS: For
group 1, the scores were 1.89 (baseline), 0.98 (6 months) and 0.56 (12 months),
and hence there were significant reductions (p = 0.0001). The gingival indices
were 1.71 (baseline), 0.76 (6 months) and 0.35 (12 months), and the reductions
were also significant (p = 0.0001). A significant association was observed
between poor oral hygiene and the degree of gingival overgrowth. The 1-year post
treatment follow-up showed that patients in group 1 did not develop gingival
overgrowth due to the use of CsA as group 2 did without prior periodontal
therapy. CONCLUSION: Oral hygiene status was the most important variable related
to the development and degree of gingival overgrowth due to the use of CsA.
PMID- 24356399
TI - Repeated administration of bone marrow-derived cells prevents disease progression
in experimental silicosis.
AB - BACKGROUND/AIMS: Bone marrow-derived cells (BMDCs) reduced mechanical and
histologic changes in the lung in a murine model of silicosis, but these
beneficial effects did not persist in the course of lung injury. We hypothesized
that repeated administration of BMDCs may decrease lung inflammation and
remodeling thus preventing disease progression. METHODS: One hundred and two
C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT])
and control (C) groups (saline, IT). C and SIL groups were further randomized to
receive BMDCs (2*10(6) cells) or saline IT 15 and 30 days after the start of the
protocol. RESULTS: By day 60, BMDCs had decreased the fractional area of
granuloma and the number of polymorphonuclear cells, macrophages (total and M1
phenotype), apoptotic cells, the level of transforming growth factor (TGF)-beta'
and types I and III collagen fiber content in the granuloma. In the alveolar
septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-beta, and the
number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1beta, IL-1R1,
caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung
mechanics improved after BMDC therapy. The presence of male donor cells in lung
tissue was not observed using detection of Y chromosome DNA. CONCLUSION: repeated
administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis,
thus improving lung mechanics through the release of paracrine factors.
PMID- 24356400
TI - Do we need new guidelines for interventional pain procedures in patients on
anticoagulants?
PMID- 24356401
TI - Evolving safe practices for chronic opioid therapy through regulation.
PMID- 24356402
TI - Adductor canal block is useful but does not achieve a complete block of the knee.
PMID- 24356403
TI - Reply to Drs Egeler, Jayakumar, and Ford.
PMID- 24356404
TI - Aberrant vein within common connective tissue sheath of the sciatic nerve at the
popliteal fossa.
PMID- 24356405
TI - Reply to "A confirmed case of injury to the long thoracic nerve following a
posterior approach to an interscalene nerve block".
PMID- 24356406
TI - Cervical paravertebral block for forearm and hand anesthesia: the jury is still
out.
PMID- 24356408
TI - Plasmonic dye-sensitized solar cells incorporated with Au-TiO2 nanostructures
with tailored configurations.
AB - We developed plasmonic dye-sensitized solar cells (DSSCs) with tailor-designed Au
TiO2 nanostructures integrated into the photoanode. Mutually antagonistic Au-TiO2
core-shell structures supported on SiO2 spheres (SiO2@TiO2@AuNP and
SiO2@AuNP@TiO2) were prepared and incorporated as additives into the photoanodes
of the DSSCs. The DSSCs employing the nanocrystalline-TiO2 (nc
TiO2)/SiO2@TiO2@AuNP and nc-TiO2/SiO2@AuNP@TiO22 as photoanodes showed remarkably
enhanced power conversion efficiencies up to about 14% and 10%, respectively,
with respect to a reference cell containing an nc-TiO2/SiO2@TiO2 photoanode. This
can be mainly attributed to the enhanced dye absorption by the intensified near
field effect of AuNPs and plasmon-enhanced photocurrent generation.
PMID- 24356407
TI - Early end-tidal carbon monoxide levels, patency of the ductus arteriosus and
regional cerebral oxygenation in preterm infants.
AB - BACKGROUND: Carbon monoxide (CO), a relaxant regulator of muscle tone and marker
of oxidative stress and inflammation, can be measured in exhaled air by
determination of end-tidal CO corrected for CO in ambient air (ETCOc). OBJECTIVE:
Increased endogenous production of CO may influence patency of the ductus
arteriosus, cerebral perfusion and, subsequently, cerebral oxygenation. The aim
was to study the relation between early ETCOc levels, hemodynamically significant
patent ductus arteriosus (hsPDA) and cerebral oxygenation (rScO2) in preterm
infants <32 weeks' gestational age and determine predictive values of ETCOc for
hsPDA. METHODS: ETCOc was measured in 91 infants within the first 24 h after
birth. A hsPDA was diagnosed according to echocardiographic indices. In 78/91
infants, rScO2 was monitored with near-infrared spectroscopy to assess cerebral
oxygenation. RESULTS: ETCOc values were significantly higher in infants who
subsequently developed hsPDA (2.3 +/- 0.7 ppm) vs. no-hsPDA (1.7 +/- 0.6 ppm), p
< 0.001. With a cut-off value of 2.5 ppm, positive and negative predictive values
of ETCOc for hsPDA were 55 and 88%, respectively. rScO2 values were not different
between the two groups (64 +/- 1 vs. 65 +/- 3%, NS). CONCLUSIONS: The higher
ETCOc values in hsPDA infants early after birth reflect the early relaxant state
of ductal muscular tone. ETCOc <2.5 ppm within 24 h after birth may predict the
subsequent absence of hsPDA. ETCOc showed no correlation with cerebral
oxygenation in both groups.
PMID- 24356409
TI - My friend and colleague, Marie Plante, drew my attention to the fact that
currently, the positions of president of the most distinguished societies of
gynecologic oncology are held by women. Introduction.
PMID- 24356410
TI - Concerning the feasibility of obtaining biopsies for research in relapsed ovarian
cancer.
PMID- 24356411
TI - Prognostic relevance of celiac lymph node involvement in ovarian cancer.
AB - OBJECTIVE: The aim of the study was to report on the oncologic outcome of the
disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer
patients. METHODS: All patients who had CLN resection as part of their
cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal
cancer were identified. Patient demographic data with particular emphasis on
operative records to detail the extent and distribution of the disease spread,
lymphadenectomy procedures, pathologic data, and follow-up data were included.
RESULTS: The median follow-up was 26.3 months. The median overall survival values
in the group with positive CLNs and in the group with negative CLNs were 26.9
months and 40.04 months, respectively. The median progression-free survival
values in the group with metastatic CLNs and in the group with negative CLNs were
8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were
associated with progression during or within 6 months after the completion of
chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were
significantly associated with poor progression-free survival, short-term
progression, and overall survival. In multivariate analysis, only the CLN status
was independently associated with short-term progression. CONCLUSIONS: Disease in
the CLN is a marker of disease severity, which is associated to a high-risk group
of patients with presumed adverse tumor biology, increased risk of lymph node
progression, and worst oncologic outcome.
PMID- 24356412
TI - The role of liver resection at the time of secondary cytoreduction in patients
with recurrent ovarian cancer.
AB - OBJECTIVE: The aim of this study is to determine the role of liver metastatectomy
in the morbidity and survival of patients with recurrent ovarian carcinoma.
METHODS: We retrospectively reviewed the records of all patients who had
undergone hepatic resection for liver metastases from ovarian carcinoma at the
time of cytoreductive surgery at our institution from 1988 to 2012. The Kaplan
Meier method was used for survival analysis. A total of 76 patients met the
inclusion criteria and had undergone liver resection as part of cytoreductive
surgery for ovarian carcinoma during the study period. Of these 76 patients, 27
underwent liver resection at the time of secondary cytoreduction, and these
patients that are the focus of this analysis. RESULTS: Median overall survival
for the study group from the time of diagnosis to the last follow-up or death was
56 months (range, 12-249 months). Twenty died of the disease with an overall
median survival of 12 months from the time of the liver resection (2-190 months),
and 7 patients were alive with the disease at the time of the last follow-up.
Based on Kaplan-Meier survival analysis, the factors associated with the longest
survival after the liver resection (2-190 months) were the interval from the
primary surgery of less than 24 months versus more than 24 months (P = 0.044) and
secondary cytoreduction to residual disease of less than 1 cm (P = 0.014).
CONCLUSIONS: Based on our analysis of a single institution's series of ovarian
cancer patients with hepatic metastasis, liver resection is feasible and safe and
should be considered as an option in selected patients at the time of secondary
cytoreduction.
PMID- 24356413
TI - Mapping the evolution of hierarchical microstructures in a Ni-based superalloy.
AB - Phase separation of gamma' precipitates determines the microstructure and
mechanical properties of nickel-based superalloys. In the course of ageing,
disordered gamma spheres form inside ordered (L12) gamma' precipitates, undergo a
morphological change to plates and finally split the gamma' precipitates. The
presence of gamma particles inside gamma' affects coarsening kinetics and
increases alloy hardness. Here we use atom probe tomography to visualize phase
separation in a Ni86.1Al8.5Ti5.4 alloy in three dimensions and to quantify the
composition of all the phases with near-atomic resolution. We find that gamma'
precipitates are supersaturated in nickel, thereby driving the formation of gamma
particles and observe a compositional evolution of the gamma particles, which
accompanies their morphological change. Our results suggest that by controlling
nickel supersaturation we can tailor the phase separation and thereby the
properties of nickel-based superalloys.
PMID- 24356414
TI - Calcium phosphate nanoparticles: a study of their synthesis, characterization and
mode of interaction with salmon testis DNA.
AB - Calcium phosphate nanoparticles (CPNPs) are presently emerging as a second
generation vector for efficient delivery and stabilization of nucleic acids
inside cells, although the detailed mode of interaction between CPNPs and DNA is
still obscure. This study discloses some features of the interaction. For this
study, we synthesized CPNPs by a modified co-precipitation method and
characterized the particles by different techniques such as dynamic light
scattering, X-ray diffraction, electron dispersive spectroscopy, Fourier
transform infra-red spectroscopy, differential thermal and thermo-gravimetric
analysis, and atomic force, scanning and transmission electron microscopy. The
characterization studies showed that the nanoparticles were spherical in shape,
about 45 nm in size and were composed of the hydroxyapatite form of calcium
phosphate; almost 90% of the starting materials were converted to nanoparticles
(NPs). The different aspects of the interaction between CPNPs and salmon testis
DNA were investigated using techniques such as UV-Vis spectrophotometry, circular
dichroism, Fourier transform infra-red spectrometry, thermal denaturation,
microviscometry, agarose gel electrophoresis, cyclic voltammetry and atomic force
microscopy. The results revealed that CPNPs interacted with DNA with ~1 : 3.3
stoichiometry with a binding constant of the order of 10(4) M(-1) through groove
interacting mode and a single nanoparticle covered about 6.2 base pairs of the
DNA chain. Moreover, the binding interaction was spontaneous, cooperative,
exothermic and enthalpy-driven and some electrostatic nature of the binding was
also evident; however, the non-polyelectrolyte contribution was dominant. The
binding interaction finally caused an increase in the melting temperature of DNA
from 70.8 degrees C to 75 degrees C and alteration of its secondary structure
from the naturally occurring B-form to C-form.
PMID- 24356415
TI - Sensitization to beer ingredients in Chinese individuals with beer allergy: a
clinical study of 20 cases.
AB - BACKGROUND: Rare case reports of allergic reactions to beer have been published,
but the nature of the eliciting substances in beer ingredients is often unknown.
OBJECTIVE: It was the aim of this study to identify sensitization patterns
against various beer ingredients in Chinese individuals with beer allergy.
METHODS: Twenty-seven Chinese individuals with a clear-cut history of beer
allergy were prescreened to answer a specific questionnaire related to the
history and symptoms of beer allergy. Twenty individuals underwent allergy
diagnostics with different food allergens and extracts of beer ingredients using
the skin prick test (SPT) and the open oral provocation test (OPT) with beer.
RESULTS: Fifteen patients (75%) showed positive reactions to one or more beer
ingredients. Of these, 9 individuals, reactive to sorghum and/or sorghum malt
also showed positive reactions to other ingredients. Seventeen individuals showed
variable symptoms after the OPT. Cutaneous erythema and urticaria were the most
common symptoms and usually persisted for over 2 h. There were no significant
differences in SPT reactivity to beer ingredients between male and female
individuals. Single patients reacted to barley, hops or yeast. CONCLUSIONS:
Sensitization to sorghum and/or sorghum malt was the most common finding in
Chinese individuals with beer allergy.
PMID- 24356417
TI - The neuroprotection exerted by memantine, minocycline and lithium, against
neurotoxicity of CSF from patients with amyotrophic lateral sclerosis, is
antagonized by riluzole.
AB - In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic
lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary
cultures of rat embryo motor cortex neurons. We also found that the antioxidant
resveratrol protected against such damaging effects and that, surprisingly,
riluzole antagonized its protecting effects. Here we have extended this study to
the interactions of riluzole with 3 other recognized neuroprotective agents,
namely memantine, minocycline and lithium. We found: (1) by itself riluzole
exerted neurotoxic effects at concentrations of 3-30 uM; this cell damage was
similar to that elicited by 30 uM glutamate and a 10% dilution of ALS/CSF; (2)
memantine (0.1-30 uM), minocycline (0.03-1 uM) and lithium (1-80 ug/ml) afforded
10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 uM,
riluzole antagonized the protection afforded by the 3 agents. These results
strongly support the view that at the riluzole concentrations reached in the
brain of patients, the neurotoxic effects of this drug could be masking the
potential neuroprotective actions of new compounds being tested in clinical
trials. Therefore, in the light of the present results, the inclusion of a group
of patients free of riluzole treatment may be mandatory in future clinical trials
performed in ALS patients with novel neuroprotective compounds.
PMID- 24356416
TI - Predicting the glomerular filtration rate in bariatric surgery patients.
AB - BACKGROUND/AIMS: Identifying the best method to estimate the glomerular
filtration rate (GFR) in bariatric surgery patients has important implications
for the clinical care of obese patients and research into the impact of obesity
and weight reduction on kidney health. We therefore performed such an analysis in
patients before and after surgical weight loss. METHODS: Fasting measured GFR
(mGFR) by plasma iohexol clearance before and after bariatric surgery was
obtained in 36 severely obese individuals. Estimated GFR was calculated using the
Modification of Diet in Renal Disease equation, the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation using serum creatinine only, the
CKD-EPI equation using serum cystatin C only and a recently derived equation that
uses both serum creatinine and cystatin C (CKD-EPIcreat-cystC) and then compared
to mGFR. RESULTS: Participants were primarily middle-aged white females with a
mean baseline body mass index of 46 +/- 9, serum creatinine of 0.81 +/- 0.24
mg/dl and mGFR of 117 +/- 40 ml/min. mGFR had a stronger linear relationship with
inverse cystatin C before (r = 0.28, p = 0.09) and after (r = 0.38, p = 0.02)
surgery compared to the inverse of creatinine (before: r = 0.26, p = 0.13; after:
r = 0.11, p = 0.51). mGFR fell by 17 +/- 35 ml/min (p = 0.007) following surgery.
The CKD-EPIcreat-cystC was unquestionably the best overall performing estimating
equation before and after surgery, revealing very little bias and a capacity to
estimate mGFR within 30% of its true value over 80% of the time. This was true
whether or not mGFR was indexed for body surface area. CONCLUSIONS: In severely
obese bariatric surgery patients with normal kidney function, cystatin C is more
strongly associated with mGFR than is serum creatinine. The CKD-EPIcreat-cystC
equation best predicted mGFR both before and after surgery.
PMID- 24356418
TI - Construction of self-supported three-dimensional TiO2 sheeted networks with
enhanced photocatalytic activity.
AB - The degradation of toxic gases and liquids using a catalyst and solar energy is
an ideal method, compared with landfill and combustion methods. The search for
active semiconductor photocatalysts that efficiently decompose contaminations
under light irradiation remains one of the most challenging tasks for solar
energy utilization. In this work, free-supporting three-dimensional (3D)
nanosheeted hierarchical porous tungsten, titanium, and tin oxide networks were
obtained by a facile Lewis acid catalytic binary template route. These networks
possess large macroscopic scale (millimeter-sized) and hierarchical
macro/mesoporous nanostructure with high surface area and large pore volume.
Photocatalytic degradation of Azo dyes demonstrated that the nanosheets
constructed hierarchical porous networks have high photocatalytic activity and
stability. The present synthetic route can serve as the new design concept for
functional 3D layered porous nanostructures.
PMID- 24356419
TI - Phospholipid scramblase 1 functionally interacts with angiogenin and regulates
angiogenin-enhanced rRNA transcription.
AB - BACKGROUND: Angiogenin (ANG) can translocate to the target cell nucleus and
accumulate in the nucleolus to enhance rRNA transcription, thus promoting cell
proliferation. However, the regulation of ANG-enhanced rRNA transcription remains
unknown. Previously we identified phospholipid scramblase 1 (PLSCR1) as a
potential ANG-interacting protein in yeast two-hybrid screening. METHODS: The
interaction was re-confirmed in yeast cells and further verified by in vitro pull
down, in vivo co-immunoprecipitation (Co-IP), fluorescent resonance energy
transfer (FRET) and immunofluorescence analyses. The rRNA transcription level was
determined by real-time quantitative PCR and Northern blot. RESULTS: PLSCR1 was
identified as a novel ANG-interacting protein. Notably, PLSCR1 interacted with
ANG in the cell nucleus and regulated rRNA transcription. Furthermore, depletion
of cellular ANG expression abolished PLSCR1-enhanced rRNA transcription, which
could be rescued by exogenous ANG. CONCLUSION: Our data suggest that PLSCR1
positively regulates rRNA transcription through interacting with ANG, thus
deepening our understanding on rRNA transcription regulation.
PMID- 24356420
TI - High fidelity patient-derived xenografts for accelerating prostate cancer
discovery and drug development.
AB - Standardized and reproducible preclinical models that recapitulate the dynamics
of prostate cancer are urgently needed. We established a bank of transplantable
patient-derived prostate cancer xenografts that capture the biologic and
molecular heterogeneity currently confounding prognostication and therapy
development. Xenografts preserved the histopathology, genome architecture, and
global gene expression of donor tumors. Moreover, their aggressiveness matched
patient observations, and their response to androgen withdrawal correlated with
tumor subtype. The panel includes the first xenografts generated from needle
biopsy tissue obtained at diagnosis. This advance was exploited to generate
independent xenografts from different sites of a primary site, enabling
functional dissection of tumor heterogeneity. Prolonged exposure of
adenocarcinoma xenografts to androgen withdrawal led to castration-resistant
prostate cancer, including the first-in-field model of complete
transdifferentiation into lethal neuroendocrine prostate cancer. Further analysis
of this model supports the hypothesis that neuroendocrine prostate cancer can
evolve directly from adenocarcinoma via an adaptive response and yielded a set of
genes potentially involved in neuroendocrine transdifferentiation. We predict
that these next-generation models will be transformative for advancing
mechanistic understanding of disease progression, response to therapy, and
personalized oncology.
PMID- 24356421
TI - GPR56 inhibits melanoma growth by internalizing and degrading its ligand TG2.
AB - Excessive accumulation of extracellular matrix (ECM) is a hallmark of tumor
microenvironment and plays active roles during tumor progression. How this
process is regulated and whether it is reversible for cancer treatment are
outstanding questions. The adhesion G protein-coupled receptor GPR56 inhibits
melanoma growth and binds to tissue transglutaminase (TG2), a major crosslinking
enzyme in ECM. To understand the function of TG2 in GPR56-mediated melanoma
inhibition, we performed xenograft studies in immunodeficient Tg2(-/-) mice. Our
results revealed an antagonistic relationship between GPR56 and TG2 in melanoma,
although TG2 and its crosslinking activity promote melanoma growth, GPR56
antagonizes this effect by internalizing and degrading it. The negative
regulation of TG2 by GPR56 associates with the decreased deposition of a major
ECM protein, fibronectin, and impaired accumulation of focal adhesion kinase,
indicating that the GPR56-TG2 interaction regulates ECM deposition and cell-ECM
adhesion. Taken together, our findings establish the roles of TG2 in GPR56
mediated melanoma inhibition. The uncovered antagonistic relationship between
GPR56 and TG2 proposes a mechanism by which ECM accumulation/crosslinking in
tumors may be reversed, and thus could have therapeutic potential for cancer
control and treatment.
PMID- 24356422
TI - Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.
AB - Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable
due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC)
that are likely responsible for relapses and drug resistance. In this study, we
investigated the preclinical activity of patient-derived cytokine-induced killer
(CIK) cells against autologous bone sarcoma and STS, including against putative
sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient
mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone
sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP
under the control of the human promoter for OCT4, a stem cell gene activated in
putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK
cells efficiently killed allogeneic and autologous sarcoma cells in vitro.
Intravenous infusion of CIK cells delayed autologous tumor growth in
immunodeficient mice. Further in vivo analyses established that CIK cells could
infiltrate tumors and that tumor growth inhibition occurred without an enrichment
of sCSCs relative to control-treated animals. These results provide preclinical
proof-of-concept for an effective strategy to attack autologous sarcomas,
including putative sCSCs, supporting the clinical development of CIK cells as a
novel class of immunotherapy for use in settings of untreatable metastatic
disease.
PMID- 24356424
TI - Fit for purpose? Dementia and the healthcare professions.
PMID- 24356423
TI - Cadherin-11 expression patterns in heart valves associate with key functions
during embryonic cushion formation, valve maturation and calcification.
AB - Proper fibroblast cell migration and differentiation are critical for valve
formation and homeostasis, but uncontrolled myofibroblastic activation may
precede osteogenic differentiation and calcification. Cadherin-11 (cad-11) is a
cell-cell adhesion protein classically expressed at mesenchymal-osteoblast
interfaces that participates in mesenchymal differentiation to osteochondral
lineages. This suggests cad-11 may have an important role in heart valve
development and pathogenesis, but its expression patterns in valves are largely
unknown. In this study, we profiled the spatial and temporal expression patterns
of cad-11 in embryonic chick and mouse heart development. We determined that cad
11 is expressed in both endocardial and mesenchymal cells of the atrioventricular
and outflow tract cushions (pre-HH30/E14), but becomes restricted to the valve
endocardial/endothelial cells during late fetal remodeling and throughout
postnatal life. We then investigated changes in cad-11 expression in a murine
aortic valve disease model (the ApoE(-/-)). Unlike wild-type mice, cad-11 becomes
dramatically re-expressed in the interstitium. Similarly, in calcified human
aortic valve leaflets, cad-11 loses endothelial confinement and becomes
significantly re-expressed in the valve interstitium. Double labeling identified
that 91% of myofibroblastic and 96% of osteoblastic cells in calcified aortic
valves were also cad-11 positive. Collectively, our results suggest that cad-11
is important for proper embryonic cushion formation and remodeling, but may also
participate in aortic valve pathogenesis if re-expressed in adulthood.
PMID- 24356425
TI - A new age approach to an age old problem: using simulation to teach geriatric
medicine to medical students.
AB - BACKGROUND: simulation-based teaching is increasingly used in medical education,
but no studies have evaluated its impact on learning in geriatric medicine. We
developed and delivered a simulation teaching session on delirium, falls, elder
abuse and breaking bad news. Simulation mannequins, professional role-players and
simulated clinical documentation were all incorporated into scenarios. We
evaluated the effect of this intervention on student learning and on students'
attitudes towards geriatric medicine. METHODS: third year Newcastle University
MBBS students at Northumbria base unit received the simulation-based teaching
session. Students' knowledge was assessed using a three question test mapped to
learning outcomes for the elder abuse, delirium and falls stations. Each student
undertook the test on three occasions: the day before the teaching session,
immediately after the session and ~1 month later, allowing evaluation of learning
over time. Test scores were also compared with those achieved by another cohort
of third year MBBS students at a different base unit, who received traditional
ward-based and didactic teaching but no simulation teaching. RESULTS: student
knowledge improved significantly after the simulation session and this was
maintained when reassessed a month later. Students who received the simulation
based training outperformed those who received usual teaching. Student feedback
was overwhelmingly positive and the vast majority of students agreed that the
session had a positive impact on their perceptions of geriatric medicine.
DISCUSSION: our findings demonstrate the efficacy of simulation-based teaching in
undergraduate geriatric medicine, its acceptability to students and its positive
influence on students' perceptions of the specialty.
PMID- 24356426
TI - A prognostic indicator of survival in metastatic colorectal cancer patients in
the era of molecular-targeted agents: the modified Glasgow Prognostic Score.
PMID- 24356427
TI - The future of cardiothoracic care: policy, politics, and performance.
PMID- 24356428
TI - Results of endoscopic radial artery harvesting in 1577 patients.
AB - OBJECTIVE: We reviewed 1577 consecutive patients undergoing coronary artery
bypass grafting (CABG) using endoscopic harvesting of the radial artery (RA) to
define our current results. METHODS: Since 2000, we have performed endoscopic RA
harvest on 1577 consecutive patients; 1476 patients had isolated CABG, and 101
patients had CABG and other procedures. The mean +/- SD age was 59.4 +/- 9.0
years; 80.2% were men and 40% had diabetes mellitus. All data were prospectively
collected. All-cause mortality was determined using the Social Security Death
Index. RESULTS: There were nine in-hospital or 30-day deaths, for an operative
mortality of 0.57%: mortality was 0.34% in isolated CABG and 3.85% in
CABG/combined procedures. The overall estimated Kaplan-Meier survival at 1, 5,
and 10 years was 99%, 95%, and 88%. In 37 patients, the RAs were not harvested or
were not used for grafting because of a positive Allen test, extensive
calcification or dissection, intramural hematoma, and scarring from previous
arterial lines or catheterization. During postoperative follow-up, five patients
(0.32%) were treated for incisional infection, and there were no ischemic hand
complications. Three patients had a perioperative myocardial infarction in the RA
graft distribution, and 15 patients had a coronary artery reintervention in the
RA graft distribution. Two other patients had a percutaneous coronary
intervention of their RAs. The overall RA patency at 10 years was 82%.
CONCLUSIONS: Endoscopic harvest of the RA is an excellent minimally invasive
conduit harvesting technique with minimal morbidity.
PMID- 24356429
TI - Can minimally invasive coronary artery bypass grafting be initiated and practiced
safely?: a learning curve analysis.
AB - OBJECTIVE: We examined the effects of learning curve on clinical outcomes and
operative time in minimally invasive coronary artery bypass grafting (MICS CABG).
METHODS: We studied 210 consecutive MICS CABG cases performed by the same
surgeon, composed of 3 cardiopulmonary bypass (CPB)-assisted single-vessel small
thoracotomy (SVST), 87 off-pump SVST, 51 CPB-assisted multivessel small
thoracotomy (MVST), and 69 off-pump MVST. For each MICS CABG technique, the
frequency of early clinical events (mortality, reopening, stroke, myocardial
infarction, and revascularization) was compared between the first 25 cases and
the remainder. Logarithmic curve regression analysis and a cumulative summation
technique were performed to assess the correlation between operative time and the
performed number of each technique. RESULTS: There was no mortality, and there
were 10 conversions to standard sternotomy, all of which were intended as off
pump MVST (P < 0.001, vs other procedures). Experience was otherwise not
associated with perioperative outcome. However, experience numbers correlated
with operative time in off-pump SVST and off-pump MVST (122 +/- 30 minutes, R =
0.18, P < 0.001, and 241 +/- 80 minutes, R = 0.38, P < 0.001, respectively) but
not in CPB-assisted MVST (258 +/- 44 minutes, R = 0.004, P = 0.7). No
complications occurred as a result of CPB assistance. CONCLUSIONS: Minimally
invasive coronary artery bypass grafting can be safely initiated, with a very low
perioperative risk. Pump assistance is a good strategy to alleviate some of the
learning curve and avoid conversions to sternotomy when initiating a multivessel
MICS CABG program.
PMID- 24356430
TI - Surgical minimally invasive pulmonary vein isolation for lone atrial
fibrillation: midterm results of a multicenter study.
AB - OBJECTIVE: Minimally invasive surgical pulmonary vein isolation (SMI-PVI) is an
emerging therapy for the treatment of symptomatic drug-refractory atrial
fibrillation (AF). Nevertheless, the midterm and long-term results of SMI-PVI
remain unknown. The aim of this retrospective multicenter study was to report on
midterm efficacy and safety of SMI-PVI. METHODS: The study design was
retrospective, multicentric, and observational. From July 2005 to November 2011,
a total of 86 patients with drug-refractory paroxysmal or persistent AF underwent
SMI-PVI in three centers. Patients were eligible for SMI-PVI if they had
symptomatic, drug-refractory AF or after failed transcatheter pulmonary vein
isolation. Success was defined as absence of AF on 24- or 96-hour Holter
monitoring during follow-up, in the absence of antiarrhythmic drugs (AADs).
RESULTS: The mean +/- SD age was 54 +/- 11 years, and 78% were men. The median AF
duration was 30 months (range, 2-203); paroxysmal AF was present in 86% of the
patients, persistent in 14%. Fifteen patients (17%) underwent previous
transcatheter ablations. After a median follow-up of 24 months (range, 6-78), 72%
of all patients were free from atrial arrhythmias without the use of AADs. With
AADs, this was 83%. Major perioperative adverse events occurred in 7 patients
(8%). CONCLUSIONS: This retrospective multicenter study shows that SMI-PVI is
effective at a median follow-up of 24 months for the treatment of mostly
paroxysmal drug-refractory AF. Perioperative adverse events do remain a point of
caution.
PMID- 24356431
TI - The accuracy of transit time flow measurement in predicting graft patency after
coronary artery bypass grafting.
AB - OBJECTIVE: Transit time flow measurement (TTFM) is a method used to assess
intraoperative blood flow after vascular anastomoses. Angiography represents the
criterion standard for the assessment of graft patency after coronary artery
bypass grafting (CABG). The purpose of this study was to compare flow
measurements from TTFM to diagnostic angiography. METHODS: From October 9, 2009,
to April 30, 2012, a total of 259 patients underwent robotic-assisted CABG
procedures at a single institution. Of these, 160 patients had both TTFM and
either intraoperative or postoperative angiography of the left internal mammary
artery to the left anterior descending coronary artery graft. Transit time flow
measurements were obtained after completion of the anastomosis and after
administration of protamine before chest closure. Transit time flow measurement
assessment included pulsatility index, diastolic fraction, and flow (milliliters
per minute). Angiograms were graded according to the Fitzgibbon criteria. The
patients were grouped according to angiographic findings, with perfect grafts
defined as FitzGibbon A and problematic grafts defined as either Fitzgibbon B or
O. RESULTS: Overall, there were 152 (95%) of 160 angiographically perfect grafts
(FitzGibbon A). Of the eight problematic grafts, five were occluded (Fitzgibbon
O) and three had significant flow-limiting lesions (FitzGibbon B). Two patients
had intraoperative graft revision after completion angiography, one had redo CABG
during the same hospitalization, and five were treated with percutaneous coronary
intervention. A significant difference was seen in mean +/- SD flow (34.3 +/-
16.8 mL/min vs 23.9 +/- 12.5 mL/min, P = 0.033) between patent and nonpatent
grafts but not in pulsatility index (1.98 +/- 0.76 vs 1.65 +/- 0.48, P = 0.16) or
diastolic fraction (73.5% +/- 8.45% vs 70.9% +/- 6.15%, P = 0.13). CONCLUSIONS:
Although TTFM can be a useful tool for graft assessment after CABG, false
negatives can occur. Angiography remains the criterion standard to assess graft
patency and quality of the anastomosis after CABG.
PMID- 24356432
TI - Minimally invasive coronary bypass using internal thoracic arteries via a left
minithoracotomy: "the Nambiar Technique".
AB - OBJECTIVE: Harvesting of the right internal thoracic artery (RITA) under direct
vision, through a left minithoracotomy, without robotic or thoracoscopic
assistance has never been done or described before. Bilateral internal thoracic
arteries (BITAs) in coronary artery bypass grafting (CABG) have shown greater
survival and freedom from reintervention. The aim was to develop a multivessel
minimally invasive CABG technique in which the BITAs are harvested under direct
vision and complete revascularization of the myocardium is done by the off-pump
method, using only BITAs (left internal thoracic artery [LITA]-RITA Y) through a
2-in left minithoracotomy, without robotic/thoracoscopic assistance-the "Nambiar
Technique." METHODS: From August 2011 to December 2012, a total of 150 patients
underwent off-pump minimally invasive multivessel CABG using BITAs, through a 2
in left minithoracotomy incision. Both internal thoracic arteries were harvested
directly under vision, and complete revascularization of the myocardium was done
using the LITA-RITA Y composite conduit, followed by flow study of the grafts.
Coronary artery stabilization for anastomoses was done by using epicardial
stabilizers introduced through the minithoracotomy. RESULTS: One hundred fifty
patients had minimally invasive total arterial myocardial revascularization using
BITAs (LITA-RITA Y composite conduit) via a left minithoracotomy. The mean number
of grafts was 2.8. A total of 81.6% of the patients had three grafts. Ejection
fraction was 34.5 +/- 5.2. There was one mortality but no major morbidity. The
RITA and LITA harvest times were 39.5 +/- 11.2 and 35.2 +/- 8.6 minutes,
respectively. The total time in the operating room (including extubation) was
331.5 +/- 42.5 minutes, and operating time was 240.8 +/- 24.6 minutes. One
hundred twenty-six patients (87.7%) were extubated on the table. The mean
hospital stay was 3.1 days. One patient (0.6%) had an elective conversion to
sternotomy because the flow in the LITA-RITA Y composite conduit was inadequate
and had saphenous vein grafts. Coronary angiograms were done in 37 patients
(25%); and computed tomographic angiograms, in 33 patients (22%), and the grafts
were patent. Stress test was done in 80 patients (53%), which had normal
findings. CONCLUSIONS: The Nambiar Technique encompassed using a 2-in left
minithoracotomy incision through which the BITAs were conveniently harvested in a
skeletonized manner under direct vision without robotic or thoracoscopic
assistance. Multivessel total arterial revascularization was then done using the
LITA-RITA Y composite conduit by the off-pump methodology. The early outcomes
have been excellent, and coronary angiograms showed widely patent grafts. This
technique is reproducible and can be done on an empty beating heart to aid in
training.
PMID- 24356433
TI - How does the surgeon's experience of abdominal operations influence the learning
curves for robot-assisted vascular anastomosis?
AB - OBJECTIVE: Endoscopic vascular anastomosis of abdominal aortic aneurysms is
rarely performed and requires standardization. Here, we examined the impact of
the surgeon's experience of abdominal aortic aneurysm surgery on the learning
curve for robot-assisted endoscopic vascular anastomosis. METHODS: Three vascular
surgeons with more than 10 years' experience (group A), three vascular surgeons
with less than 10 years' experience (group B), and three medical students with no
experience (group C) of performing vascular surgery used the da Vinci surgical
system to anastomose 8-mm-diameter vascular prostheses in an end-to-end manner
with continuous 5-0 Prolene sutures. The procedure was performed five times by
each participant. Outcomes were anastomosis time, number of actions, visual
score, and pressure test. Snapping of the prolene thread was recorded as a
procedural failure. RESULTS: Procedural failure occurred only in group C (3/15
trials, 20%; P < 0.0001). Learning curves were apparent in all three groups for
anastomosis time and in groups A and C for the number of actions. Between trials
1 and 5, learning curves were apparent in all three groups for anastomosis time
and in groups A and C for the number of actions but were not apparent for leakage
or visual score in any group. Visual score and leakage were not significantly
different among the three groups in each trial (P = 0.10 and P = 0.45,
respectively). CONCLUSIONS: By using the da Vinci surgical system, experienced
vascular surgeons and surgically naive students showed marked improvements in
vascular anastomosis techniques with a short period of training.
PMID- 24356434
TI - Minimally invasive valve surgery with bypass to the right coronary artery.
AB - Herein, we report the case of a 60-year-old woman who presented with increasing
dyspnea on exertion. Echocardiography revealed significant aortic and mitral
regurgitation, which were most likely secondary to previous radiation therapy for
breast cancer. On cardiac catheterization a 90% ostial right coronary artery
lesion was found and treated with a drug-eluting stent. During minimally invasive
valve surgery, via a right anterior thoracotomy, it was noted that the stent had
restenosed. Therefore, the right coronary artery was bypassed with a segment of
venous graft through the same incision.
PMID- 24356435
TI - Premeasured neochordae loop maker: a new technology in mitral valve repair.
AB - The exact length of neochordae loops plays the major role in the success of
mitral valve repair. The Neochordae Loop Maker is a novel device that models the
left ventricular structure in an individual patient. Preoperative transthoracic
echocardiography is used to identify the geometry of each papillary muscle and
set up the device for the patient. All required neochordae loops are made in the
operating room before initiating the cardiopulmonary bypass. In the calibration
phase, seven consecutive patients who were candidates for mitral valve
replacement underwent transthoracic echocardiography. The device was set up for
each patient, and the length of their normal chordae and their respective
neochordae was compared by the Bland-Altman analysis. From seven excised mitral
valves, 21 chordae were considered normal (gold standard). The length of these
gold standards (1.92 +/- 0.67 cm) and their respective neochordae (1.93 +/- 0.69
cm) showed agreement by the Bland-Altman analysis. The proposed technology showed
satisfactory preliminary results in creating the premeasured neochorda loops
inasmuch as it reduced the complexity of minimally invasive surgeries.
PMID- 24356436
TI - Editorial.
PMID- 24356437
TI - Free-standing and binder-free sodium-ion electrodes with ultralong cycle life and
high rate performance based on porous carbon nanofibers.
AB - Free-standing and binder-free porous carbon nanofibers (P-CNFs) electrodes were
prepared by pyrolysis of PAN-F127/DMF nanofibers via an electrospinning process
as potential anodes for Na-ion batteries (NIB). The P-CNFs delivers a reversible
capacity of 266 mA h g(-1) after 100 cycles at 0.2 C, corresponding to ~80% of
the initial charge capacity. When cycled at a current density as high as 500 mA
g(-1) (2 C), it still delivers a reversible capacity of ~140 mA h g(-1) after
1000 cycles. The improvement of electrochemical performance is attributed to the
special design and microstructure of P-CNFs, which conferred a variety of
advantages: hierarchical porous channels enabling short transport length for ions
and electrons, 3D interconnected structure resulting in low contact resistances,
good mechanical properties leading to the excellent morphology stability.
PMID- 24356438
TI - Fetal fraction estimate in twin pregnancies using directed cell-free DNA
analysis.
AB - OBJECTIVE: To estimate fetal fraction (FF) in monozygotic and dizygotic twin
pregnancies. METHODS: Maternal plasma samples were obtained from 35 monochorionic
twin pregnancies with male fetuses (monozygotic) and 35 dichorionic pregnancies
discordant for fetal sex (dizygotic) at 11-13 weeks' gestation. Cell-free DNA was
extracted and chromosome-selective sequencing with digital analysis of selected
regions (DANSRTM) was carried out. The fetal-fraction optimized risk of trisomy
evaluation (FORTETM) algorithm was used to estimate FF using polymorphic alleles.
In dizygotic twins the FORTE algorithm was modified to estimate the smallest FF
contribution of the 2 fetuses. In both types of twins, FF was also determined by
analysis of Y-chromosome sequences. RESULTS: In monozygotic twins, the median
total FF was 14.0% (range 8.2-27.0%) and in dizygotic twins the median smallest
FF was 7.9% (4.9-14.0%). There were significant associations in FF between the
methods using polymorphic alleles and Y-chromosome sequences for both monozygotic
(r=0.951, p<0.0001) and dizygotic (r=0.743, p<0.0001) twins. CONCLUSIONS: The
study demonstrates the feasibility of an approach for cfDNA testing in twin
pregnancies. This involves estimation of total FF in monozygotic twins and
estimation of the lower FF of the 2 fetuses in dizygotic twins.
PMID- 24356440
TI - Abundance of MMPs and cysteine cathepsins in caries-affected dentin.
AB - Degradation of dentin matrix components within caries dentin has been correlated
with the activity of host-derived proteases, such as matrix metalloproteases
(MMPs) and cysteine cathepsins (CTs). Since this relationship has not been fully
established, we hypothesized that the abundance of MMPs and CTs in caries
affected dentin must be higher than in intact dentin. To test this premise, we
obtained 5 slices (200 um) from 5 intact teeth and from 5 caries-affected teeth
(1 slice/tooth) and individually incubated them with primary antibodies for CT-B,
CT-K, MMP-2, or MMP-9. Negative controls were incubated with pre-immune serum.
Specimens were washed and re-incubated with the respective fluorescent secondary
antibody. Collagen identification, attained by the autofluorescence capture
technique, and protease localization were evaluated by multi-photon confocal
microscopy. The images were analyzed with ZEN software, which also quantitatively
measured the percentages of collagen and protease distribution in dentin
compartments. The abundance of the test enzymes was markedly higher in caries
affected than in intact dentin. CT-B exhibited the highest percentage of co
localization with collagen, followed by MMP-9, MMP-2, and CT-K. The high
expression of CTs and MMPs in caries-affected teeth indicates that those host
derived enzymes are intensely involved with caries progression.
PMID- 24356439
TI - Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth.
AB - Glioblastoma (GBM) is the most common and deadly malignant brain cancer, with a
median survival of <2 years. GBM displays a cellular complexity that includes
brain tumour-initiating cells (BTICs), which are considered as potential key
targets for GBM therapies. Here we show that the transcription factors FOXG1 and
Groucho/TLE are expressed in poorly differentiated astroglial cells in human GBM
specimens and in primary cultures of GBM-derived BTICs, where they form a
complex. FOXG1 knockdown in BTICs causes downregulation of neural stem/progenitor
and proliferation markers, increased replicative senescence, upregulation of
astroglial differentiation genes and decreased BTIC-initiated tumour growth after
intracranial transplantation into host mice. These effects are phenocopied by
Groucho/TLE knockdown or dominant inhibition of the FOXG1:Groucho/TLE complex.
These results provide evidence that transcriptional programmes regulated by FOXG1
and Groucho/TLE are important for BTIC-initiated brain tumour growth, implicating
FOXG1 and Groucho/TLE in GBM tumourigenesis.
PMID- 24356441
TI - Maternal oral bacterial levels predict early childhood caries development.
AB - OBJECTIVE: To calculate the association of maternal salivary bacterial challenge
(mutans streptococci [MS] and lactobacilli [LB]) from pregnancy through 24
months' postpartum with child caries incidence (>=1 cavitated or restored teeth)
at 36 months. MATERIALS & METHODS: Dental, salivary bacterial, sociodemographic,
and behavioral measures were collected at three- to six-month intervals from a
birth cohort of low-income Hispanic mother-child dyads (N = 243). We calculated
the relative child caries incidence, adjusted for confounding, following higher
maternal challenge of MS (>4500 colony-forming units per milliliter of saliva
[CFU/mL]) and LB (>50 CFU/mL) based on multivariable models. RESULTS: Salivary MS
and LB levels were greater among mothers of caries-affected children versus
caries-free children. Mothers with higher salivary MS challenge were more likely
to have MS-positive children (>0 CFU/mL), but maternal LB challenge was not a
statistically significant predictor of child LB-positive status. Adjusting for
sociodemographics, feeding and care practices, and maternal dental status, higher
maternal salivary challenge of both MS and LB over the study period predicted
nearly double the child caries incidence versus lower MS and LB (cumulative
incidence ratio: 1.9; 95% confidence interval: 1.1, 3.8). CONCLUSION: Maternal
salivary bacterial challenge not only is associated with oral infection among
children but also predicts increased early childhood caries occurrence.
PMID- 24356443
TI - Apropos "Vaccination for safe travel to India".
PMID- 24356442
TI - Sal k 5, a member of the widespread Ole e 1-like protein family, is a new
allergen of Russian thistle (Salsola kali) pollen.
AB - BACKGROUND: Salsola kali is an Amaranthaceae weed with important repercussions
for pollinosis in temperate areas. Ole e 1-like members are relevant allergens in
pollen from different species. We aimed to characterize and produce as
recombinant allergen S. kali Ole e 1-like protein. METHODS: The natural allergen
was purified at homogeneity after three chromatographic steps. Specific cDNA was
sequenced and expressed in Pichia pastoris yeast. Structural relationships of
natural and recombinant forms were carried out by 2D electrophoresis and
spectroscopic analyses. Its immunological relevance was analyzed by ELISA and
immunoblotting using an IgG antiserum and monoclonal antibodies specific to Ole e
1, as well as sera from 57 allergic patients recruited from two Spanish regions
where this pollinosis is frequent. RESULTS: The purified allergen, Sal k 5, is an
acidic glycoprotein of 151 amino acid residues and 17,628 Da of molecular mass.
Its amino acid sequence exhibits 68 and 32% identity with the allergens of Che a
1 and Ole e 1, respectively. The recombinant protein was correctly processed and
its structural and immunologic equivalence to the natural form was proven. A
sensitization frequency between 30 and 40% was observed in pollinic patients from
the center and east coast of Spain. CONCLUSIONS: Sal k 5 is a member of the Ole e
1-like protein family which can be considered an important allergen from S. kali.
Its inclusion in diagnosis protocols would allow the accurate defining of
patients allergic to this pollen.
PMID- 24356444
TI - pH luminescence switching, dihydrogen phosphate sensing, and cellular uptake of a
heterobimetallic ruthenium(II)-rhenium(I) complex.
AB - A new heterobimetallic ruthenium(II)-rhenium(I) complex of
[Ru(bpy)2(HL)Re(CO)3Cl](ClO4)2.6H2O (RuHLRe) {bpy = 2,2'-bipyridine and HL = 2-(4
(2,6-di(pyridin-2-yl)pyridin-4-yl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}
was synthesised and characterised by elemental analysis, proton nuclear magnetic
resonance spectroscopy, and mass spectrometry. The ground- and excited-state acid
base properties of RuHLRe were studied using UV-Vis absorption spectrophotometric
and spectrofluorimetric titrations in a 100 : 1 (v/v) Britton-Robinson buffer
CH3CN solution combined with luminescence lifetime measurements. The complex
exhibited two-step separate protonation-deprotonation processes in both the
ground and excited states. The complex acted as pH-induced "off-on-off"
luminescence switches (I(on)/I(off) = 31.0 and 14.6), with one of the switching
actions being driven by pH variations over the physiological pH range (5.3-8.0).
Importantly, cellular imaging and cytotoxicity experiments demonstrated that
RuHLRe rapidly and selectively illuminated the membrane of HeLa cells over fixed
cells and exhibited reduced cytotoxicity at the imaging concentration compared to
the Re(I)-free parent Ru(II) complex. In addition, RuHLRe acted as an efficient
"turn on" emission sensor for H2PO4(-) and "turn off" emission sensor for F(-)
and OAc(-).
PMID- 24356445
TI - Annexin V-TRAIL fusion protein is a more sensitive and potent apoptotic inducer
for cancer therapy.
AB - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
promising cancer therapeutic agent, which kills cancer cells selectively, while
leaving normal cells unharmed. However, the emerging resistance of tumor cells
and patients to TRAIL-induced apoptosis limits its further application. In this
study, we developed a chimeric protein Annexin V-TRAIL (designated as TP8) with
higher efficacy than TRAIL both in vitro and in vivo. In vitro, the EC50 of TP8
on a series of tumor cells was much lower than wild-type TRAIL. Annexin V
provided this recombinant protein with higher efficacy, while leaving tumor
specificity of TRAIL unchanged since TP8 had no effects on normal cells. In vivo,
TP8 effectively suppressed tumor growth and prolonged tumor doubling time and
tumor growth delay time in mouse xenografts involving multiple cancer cell types
including A549, Colo205 and Bel7402. This study provides a new rational strategy
to treat TRAIL-resistant cancers.
PMID- 24356446
TI - Uncovering the role of APC-Cdh1 in generating the dynamics of S-phase onset.
AB - Cdh1, a coactivator of the anaphase-promoting complex (APC), is a potential tumor
suppressor. Cdh1 ablation promotes precocious S-phase entry, but it was unclear
how this affects DNA replication dynamics while contributing to genomic
instability and tumorigenesis. We find that Cdh1 depletion causes early S-phase
onset in conjunction with increase in Rb/E2F1-mediated cyclin E1 expression, but
reduced levels of cyclin E1 protein promote this transition. We hypothesize that
this is due to a weakened cyclin-dependent kinase inhibitor (CKI)-cyclin
dependent kinase 2 positive-feedback loop, normally generated by APC-Cdh1
mediated proteolysis of Skp2. Indeed, Cdh1 depletion increases Skp2 abundance
while diminishing levels of the CKI p27. This lowers the level of cyclin E1
needed for S-phase entry and delays cyclin E1 proteolysis during S-phase
progression while corresponding to slowed replication fork movement and reduced
frequency of termination events. In summary, using both experimental and
computational approaches, we show that APC-Cdh1 establishes a stimulus-response
relationship that promotes S phase by ensuring that proper levels of p27
accumulate during G1 phase, and defects in its activation accelerate the timing
of S-phase onset while prolonging its progression.
PMID- 24356447
TI - SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE
promoter elements.
AB - Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein
contributing to genome stability via repair of DNA lesions via the base excision
repair pathway. It also plays a role in gene expression regulation and RNA
metabolism. Another, poorly characterized function is its ability to bind to
negative calcium responsive elements (nCaRE) of some gene promoters. The presence
of many functional nCaRE sequences regulating gene transcription can be
envisioned, given their conservation within ALU repeats. To look for functional
nCaRE sequences within the human genome, we performed bioinformatic analyses and
identified 57 genes potentially regulated by APE1. We focused on sirtuin-1
(SIRT1) deacetylase due to its involvement in cell stress, including senescence,
apoptosis, and tumorigenesis, and its role in the deacetylation of APE1 after
genotoxic stress. The human SIRT1 promoter presents two nCaRE elements stably
bound by APE1 through its N-terminus. We demonstrate that APE1 is part of a
multiprotein complex including hOGG1, Ku70, and RNA Pol II, which is recruited on
SIRT1 promoter to regulate SIRT1 gene functions during early response to
oxidative stress. These findings provide new insights into the role of nCaRE
sequences in the transcriptional regulation of mammalian genes.
PMID- 24356448
TI - A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a
new mechanism to regulate water permeability.
AB - Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue.
Here we report the identification and functional analysis of an alternatively
spliced transcript of human AQP4, AQP4-Delta4, that lacks exon 4. In transfected
cells AQP4-Delta4 is mainly retained in the endoplasmic reticulum and shows no
water transport properties. When AQP4-Delta4 is transfected into cells stably
expressing functional AQP4, the surface expression of the full-length protein is
reduced. Furthermore, the water transport activity of the cotransfectants is
diminished in comparison to transfectants expressing only AQP4. The observed down
regulation of both the expression and water channel activity of AQP4 is likely to
originate from a dominant-negative effect caused by heterodimerization between
AQP4 and AQP4-Delta4, which was detected in coimmunoprecipitation studies. In
skeletal muscles, AQP4-Delta4 mRNA expression inversely correlates with the level
of AQP4 protein and is physiologically associated with different types of
skeletal muscles. The expression of AQP4-Delta4 may represent a new regulatory
mechanism through which the cell-surface expression and therefore the activity of
AQP4 can be physiologically modulated.
PMID- 24356449
TI - The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary
transition zone.
AB - In differentiated human cells, primary cilia fulfill essential functions in
converting mechanical or chemical stimuli into intracellular signals. Formation
and maintenance of cilia require multiple functions associated with the centriole
derived basal body, from which axonemal microtubules grow and which assembles a
gate to maintain the specific ciliary proteome. Here we characterize the function
of a novel centriolar satellite protein, synovial sarcoma X breakpoint
interacting protein 2 (SSX2IP), in the assembly of primary cilia. We show that
SSX2IP localizes to the basal body of primary cilia in human and murine ciliated
cells. Using small interfering RNA knockdown in human cells, we demonstrate the
importance of SSX2IP for efficient recruitment of the ciliopathy-associated
satellite protein Cep290 to both satellites and the basal body. Cep290 takes a
central role in gating proteins to the ciliary compartment. Consistent with that,
loss of SSX2IP drastically reduces entry of the BBSome, which functions to target
membrane proteins to primary cilia, and interferes with efficient accumulation of
the key regulator of ciliary membrane protein targeting, Rab8. Finally, we show
that SSX2IP knockdown limits targeting of the ciliary membrane protein and BBSome
cargo, somatostatin receptor 3, and significantly reduces axoneme length. Our
data establish SSX2IP as a novel targeting factor for ciliary membrane proteins
cooperating with Cep290, the BBSome, and Rab8.
PMID- 24356450
TI - Rab11 facilitates cross-talk between autophagy and endosomal pathway through
regulation of Hook localization.
AB - During autophagy, double-membrane autophagosomes deliver sequestered cytoplasmic
content to late endosomes and lysosomes for degradation. The molecular mechanism
of autophagosome maturation is still poorly characterized. The small GTPase Rab11
regulates endosomal traffic and is thought to function at the level of recycling
endosomes. We show that loss of Rab11 leads to accumulation of autophagosomes and
late endosomes in Drosophila melanogaster. Rab11 translocates from recycling
endosomes to autophagosomes in response to autophagy induction and physically
interacts with Hook, a negative regulator of endosome maturation. Hook anchors
endosomes to microtubules, and we show that Rab11 facilitates the fusion of
endosomes and autophagosomes by removing Hook from mature late endosomes and
inhibiting its homodimerization. Thus induction of autophagy appears to promote
autophagic flux by increased convergence with the endosomal pathway.
PMID- 24356451
TI - CAPS and Munc13 utilize distinct PIP2-linked mechanisms to promote vesicle
exocytosis.
AB - Phosphoinositides provide compartment-specific signals for membrane trafficking.
Plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) is required for
Ca(2+)-triggered vesicle exocytosis, but whether vesicles fuse into PIP2-rich
membrane domains in live cells and whether PIP2 is metabolized during Ca(2+)
triggered fusion were unknown. Ca(2+)-dependent activator protein in secretion 1
(CAPS-1; CADPS/UNC31) and ubMunc13-2 (UNC13B) are PIP2-binding proteins required
for Ca(2+)-triggered vesicle exocytosis in neuroendocrine PC12 cells. These
proteins are likely effectors for PIP2, but their localization during exocytosis
had not been determined. Using total internal reflection fluorescence microscopy
in live cells, we identify PIP2-rich membrane domains at sites of vesicle fusion.
CAPS is found to reside on vesicles but depends on plasma membrane PIP2 for its
activity. Munc13 is cytoplasmic, but Ca(2+)-dependent translocation to PIP2-rich
plasma membrane domains is required for its activity. The results reveal that
vesicle fusion into PIP2-rich membrane domains is facilitated by sequential PIP2
dependent activation of CAPS and PIP2-dependent recruitment of Munc13. PIP2
hydrolysis only occurs under strong Ca(2+) influx conditions sufficient to
activate phospholipase Ceta2 (PLCeta2). Such conditions reduce CAPS activity and
enhance Munc13 activity, establishing PLCeta2 as a Ca(2+)-dependent modulator of
exocytosis. These studies provide a direct view of the spatial distribution of
PIP2 linked to vesicle exocytosis via regulation of lipid-dependent protein
effectors CAPS and Munc13.
PMID- 24356453
TI - Efficiency improvement of silicon nanostructure-based solar cells.
AB - Solar cells based on a high-efficiency silicon nanostructure (SNS) were developed
using a two-step metal-assisted electroless etching (MAEE) technique, phosphorus
silicate glass (PSG) doping and screen printing. This process was used to produce
solar cells with a silver nitrate (AgNO3) etching solution in different
concentrations. Compared to cells produced using the single MAEE technique, SNS
based solar cells produced with the two-step MAEE technique showed an increase in
silicon surface coverage of ~181.1% and a decrease in reflectivity of ~144.3%.
The performance of the SNS-based solar cells was found to be optimized (~11.86%)
in an SNS with a length of ~300 nm, an aspect ratio of ~5, surface coverage of
~84.9% and a reflectivity of ~6.1%. The ~16.8% increase in power conversion
efficiency (PCE) for the SNS-based solar cell indicates good potential for mass
production.
PMID- 24356452
TI - Mutations that disrupt Ca2+-binding activity endow Doc2beta with novel functional
properties during synaptic transmission.
AB - Double C2-domain protein (Doc2) is a Ca(2+)-binding protein implicated in
asynchronous and spontaneous neurotransmitter release. Here we demonstrate that
each of its C2 domains senses Ca(2+); moreover, the tethered tandem C2 domains
display properties distinct from the isolated domains. We confirm that
overexpression of a mutant form of Doc2beta, in which two acidic Ca(2+) ligands
in the C2A domain and two in the C2B domain have been neutralized, results in
markedly enhanced asynchronous release in synaptotagmin 1-knockout neurons.
Unlike wild-type (wt) Doc2beta, which translocates to the plasma membrane in
response to increases in [Ca(2+)](i), the quadruple Ca(2+)-ligand mutant does not
bind Ca(2+) but is constitutively associated with the plasma membrane; this
effect is due to substitution of Ca(2+) ligands in the C2A domain. When
overexpressed in wt neurons, Doc2beta affects only asynchronous release; in
contrast, Doc2beta Ca(2+)-ligand mutants that constitutively localize to the
plasma membrane enhance both the fast and slow components of synaptic
transmission by increasing the readily releasable vesicle pool size; these
mutants also increase the frequency of spontaneous release events. Thus,
mutations in the C2A domain of Doc2beta that were intended to disrupt Ca(2+)
binding result in an anomalous enhancement of constitutive membrane-binding
activity and endow Doc2beta with novel functional properties.
PMID- 24356454
TI - New reference values for calcium.
AB - The nutrition societies of Germany, Austria and Switzerland are the joint editors
of the 'reference values for nutrient intake'. They have revised the reference
values for the intake of calcium and published them in June 2013. The reference
values for the calcium intake for infants are derived from the calcium content of
breast milk. For infants from 4 to <12 months of age, the calcium intake from
solid foods is included in addition to the calcium intake from breast milk. Thus,
the reference values for infants are estimated values; they are 220 mg/day for
infants to <4 months and 330 mg/day for infants from 4 to <12 months of age. As a
parameter for determining the calcium requirement in children and adolescents,
calcium retention is taken into account. The average requirement is calculated by
the factorial method. A balanced calcium metabolism is calculated based upon
calcium balance studies and used as a parameter for the determination of the
calcium requirement in adults. On the basis of the average requirement,
recommended calcium intake levels for children, adolescents and adults are
derived. Depending on age, the recommended calcium intake ranges between 600
mg/day for children aged 1 to <4 years and 1,200 mg/day for adolescents aged 13
to <19 years; for adults, it is 1,000 mg/day.
PMID- 24356455
TI - Demethylation of miR-9-3 and miR-193a genes suppresses proliferation and promotes
apoptosis in non-small cell lung cancer cell lines.
AB - BACKGROUND: MicroRNAs miR-9-3 and miR-193a have recently been found to be
hypermethylated in a variety of non-small cell lung cancer (NSCLC) cells and
primary human tumors. The objectives of this study were to investigate the role
of demethylation of miR-9-3 and miR-193a genes in regulating proliferation and
apoptosis in NSCLCs, and to decipher the potential mechanisms underlying the
properties. METHODS: MTT and population doubling time by flow cytometry were used
to assess cell proliferation. Enzyme-Linked Immunosorbent Assay and caspase-3
activity assay were employed to evaluate apoptosis. Real-time RT-PCR and Western
blot were used to quantify gene expression at mRNA and protein levels,
respectively. Methylation-specific PCR was utilized to assess methylation status.
RESULTS: We found that demethylation agent 5-Aza-2'-deoxycytidine (5-AzaC)
reduced cell numbers and prolonged population doubling time (PDT), and promoted
doxorubicin-induced apoptosis in seven NSCLC cell lines with different
methylation statuses on miR-9-3 and miR-193a promoter regions: NCI-H1993/NCI
H1915 (miR-9-3(+)/miR-193a(+)), NCI-H1975/NCI-H200 (miR-9-3(+)/miR-193a(-)),
A427/NCI-H2073 (miR-9-3(-)/miR-193a(+)), and NCI-H1703 (miR-9-3(-)/miR-193a(-)).
Treatment with 5-AzaC concomitantly upregulated expression of miR-9-3 and miR
193a, and downregulated their respective target genes NF-kappaB and Mcl-1. The
effects of 5-AzaC were abolished by concomitant knockdown of miR-9-3 and miR-193a
using the complex antisense technique, whereas forced ectopic expression of miR-9
3 and miR-193a mimicked the effects of 5-AzaC. We further observed that the
strength of proliferation inhibition and apoptosis promotion elicited by 5-AzaC
was in the order of NCI-H1993/NCI-H1915 > A427/NCI-H2073 > NCI-H1975/NCI-H200 >
NCI-H1703. CONCLUSIONS: Methylation-silencing of miR-9-3 and miR-193a may be an
important epigenetic mechanisms favoring NSCLC cell growth and survival for
carcinogenesis and cancer progression, and demethylation to reactivate expression
of miR-9-3 and miR-193a genes contributes, at least partially, to the anti-cancer
properties of 5-AzaC and thereby may be worthy of future studies for the
possibility of being a new therapeutic strategy for the treatment of human
NSCLCs.
PMID- 24356456
TI - Moderately severe acute pancreatitis associated with riluzole.
PMID- 24356457
TI - Occult hepatitis B virus infection in Chinese cryptogenic intrahepatic
cholangiocarcinoma patient population.
AB - BACKGROUND: There is no information available about occult hepatitis B virus
(HBV) infection (OBI) in individuals with intrahepatic cholangiocarcinoma (ICC).
GOALS: To investigate the correlation between OBI and ICC. STUDY: A retrospective
case-control study was conducted. The cases were 183 cryptogenic ICC patients
(group I), and the controls were 549 healthy individuals (group II). The cases
and controls were matched for age, sex, and inhabitancy. Adjusted odds ratios and
95% confidence intervals were calculated. Intrahepatic total HBV DNA in 63
paraffin-embedded samples was collected from patients in group I (n=44), HBV
associated ICC patients (n=3), and hepatic cavernous hemangioma patients with
seronegative HBsAg (hepatitis B S antigen) (group III; n=16). We determined the
levels of serum and intrahepatic HBV DNA and compared the level of intrahepatic
HBV DNA in 44 cryptogenic patients from group I with the level in the patients
from group III. RESULTS: Compared with group II, group I had a lower prevalence
of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe
(antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis
B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc
positivity were associated with ICC. The odds ratios and 95% confidence intervals
for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066,
respectively. Compared with group III, cryptogenic ICC cases showed more frequent
detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002).
CONCLUSIONS: OBI may represent an important risk factor for ICC. HBsAg
seroclearance does not signify eradication of HBV and may not entirely prevent
the development of ICC.
PMID- 24356458
TI - Self-efficacy and adherence to antiviral treatment for chronic hepatitis C.
AB - GOALS: To investigate the role of self-efficacy (SE) during hepatitis C virus
(HCV) treatment. BACKGROUND: Adherence to chronic HCV treatment is critical. SE
is an important predictor of medication adherence in a number of chronic disease
populations and medication regimens, but its role during HCV treatment remains
unknown. STUDY: Data from the prospective Virahep-C study were analyzed to
examine relationships between SE and patient-driven deviations (ie, missed doses
measured using electronic pill caps, and nonpersistence) from adherence to HCV
antiviral treatment. SE was measured using the 17-item HCV Treatment Self
Efficacy scale. This measure provides a global estimate of a patient's confidence
to undergo and adhere to HCV treatment, and can estimate SE in 4 underlying
domains: communication SE (ie, confidence to communicate with health care
provider), physical coping SE (ie, confidence to cope with physical side
effects), psychological coping SE (ie, confidence to cope with psychiatric side
effects), and treatment adherence SE (ie, confidence to take all medications as
prescribed and attend doctor visits). Generalized estimating equations and Cox
proportional hazards models were used to assess associations between SE and
missed doses and nonpersistence, respectively. RESULTS: SE was associated with
being in a relationship, educated, privately insured, and less depressed. Higher
communication SE at TW24 reduced the risk of missed doses between TW24 and TW48.
Higher baseline treatment adherence SE reduced the likelihood of nonpersistence
between baseline and TW24. CONCLUSIONS: SE's relationship to HCV treatment
adherence has promising clinical and research implications.
PMID- 24356459
TI - Long-term follow-up of asymptomatic pancreatic neuroendocrine tumors in multiple
endocrine neoplasia type I syndrome.
AB - BACKGROUND AND AIMS: Pancreatic neuroendocrine tumors (PNETs) in asymptomatic
patients may contribute to mortality. Endoscopic ultrasound (EUS) is the most
accurate test to identify and monitor tumor size. The aim of this study was to
examine the rate of growth and development of new tumors in multiple endocrine
neoplasia type I (MEN 1). MATERIALS AND METHODS: A retrospective cohort study in
a tertiary academic center. Patients identified in endoscopic databases were
included if they had 2 or more EUS examinations with untreated asymptomatic
tumors identified. The growth rate and incidence of new lesions was analyzed.
RESULTS: A total of 11 patients were studied (7 female, 4 male). Initially, 18
lesions with an average size of 10.3 mm (range, 5 to 24 mm) were found. Mean
surveillance was 79 months (range, 18 to 134 mo). The growth rate of index
lesions was 1.32 mm/y; 11 lesions exhibited stability or a decrease in size.
Twelve new lesions were identified in 7 patients during the surveillance period
with an average growth rate of 3.0 mm/y. The earliest new lesion was identified
at 12 months and the latest at 70 months after index EUS. New lesions had a
faster growth rate than those seen on initial EUS (P=0.01). CONCLUSIONS: Multiple
endocrine neoplasia type I patients exhibit an overall low rate of growth of
pancreatic neuroendocrine tumors. Growth rate of newly diagnosed lesions was
significantly faster, suggesting a variation in phenotypic expression of the
disease. Therapy should be individualized based upon the tumor size and location,
symptoms, overall clinical status, and operative risk.
PMID- 24356460
TI - Organ donation and transplantation in the UK-the last decade: a report from the
UK national transplant registry.
AB - Over the decade between 2003 and 2012, the UK has seen major changes in how organ
donation and transplantation is delivered. The number of deceased organ donors
has increased from 709 (12.0 per million population [pmp]) to 1,164 (18.3 pmp);
this increase has been predominantly a result of an increase in donors after
circulatory death (DCD) (from 1.1 pmp to 7.9 pmp) while the numbers of donors
after brain death (DBD) has remained broadly stable (around 10.5 pmp). The donor
population has become older (from 14% 60 years or over to 35%) and heavier (from
14% with body mass index >=30 kg/m2 to 23%). Despite these changes in demographic
factors, the number of organs retrieved from DBD donors has risen from a mean of
3.6 to 4.0 per donor and for DCD donors from 2.2 to 2.6. The number of
transplants in adults in 2012 was 2,709 (967 DBD, 708 DCD, and 1,034 living) for
kidney alone, 246 pancreas (including 172 kidney and pancreas), 792 (611 DBD, 142
DCD, 36 living, and 3 domino) for liver, 136 for heart only, and 179 (145 DBD and
34 DCD) for lung only. Median waiting times to transplant for adult patients were
1,167, 339, 141, 293, and 311 days, respectively. The proportion of adult non
urgent registrants in 2009 (2007 for kidneys) who were removed from the waiting
list or died awaiting a graft within 1 year was 3% for kidneys, 6% for pancreas,
19% for liver, 27% for heart, and 24% for lung. Outcomes after solid organ
transplants are improving; for adult patients grafted between 2003 and 2005, 5
year graft survival for kidney is 84% (DBD), 87% (DCD), and 92% (living donor),
for simultaneous kidney and pancreas 72%, and for pancreas alone 50% (DBD). Five
year patient survival for liver is 77% (DBD) and 68% (DCD), heart 67%, and lung
52% (DBD). Although rates of organ donation and transplantation have increased in
the UK, this has been almost solely because of a rise in DCD donation. Although
donor age and weight is increasing, graft survival has generally improved.
Despite a recent fall in the number of patients on the transplant waiting list,
there remains a significant gap between the need for transplantation and the
number of organs available from deceased and living donors. The implementation of
a new strategy following the recommendations of the Organ Donation Task Force in
2008 has had a major impact in bringing together clinicians involved in both
organ donation and transplantation, and these changes and clinical enthusiasm
have been instrumental in achieving success. With an emphasis on the need to
increase the family consent rate for organ donation, which has failed to show any
improvement over the last 5 years, a new UK strategy for organ donation and
transplantation, introduced in 2013, will further increase organ transplantation
in the UK.
PMID- 24356461
TI - Associations between initial change in physical activity level and subsequent
change in regional body fat distributions.
AB - BACKGROUND: Few studies have examined which lifestyle factors relate to the
development of fat distribution. Therefore, the identification of the
determinants of changes in fat deposition is highly relevant. METHODS: The
association between the change in physical activity (PA) and the subsequent
changes in regional body fat distributions was examined. In total, 1,236 men and
1,201 women were included at baseline and participated in the Danish MONICA
(MONItoring Trends and Determinants in CArdiovascular Disease) study. A
questionnaire was used to assess PA at 5 and 11 years after baseline examination,
while waist circumference (WC) and hip circumference (HC) were measured at both
follow-ups. RESULTS: Among men, WC increased in the constant active group to a
lesser extent than in the non-constant active group (3.4 vs. 4.1 cm; p = 0.03)
concerning leisure time physical activities (LTPA). A similar pattern was
observed for both WC and HC in relation to occupational physical activities (OPA)
(p = 0.02). Among women, the results went in the same direction for LTPA, whereas
the associations with OPA were in the opposite direction (p = 0.001). CONCLUSION:
LTPA and OPA were associated with reduced subsequent 6-year changes in regional
fat distribution for men. For women, no associations were observed in relation to
WC; however, OPA seemed to increase HC among women.
PMID- 24356462
TI - First-trimester screening for trisomies 21, 18 and 13 by ultrasound and
biochemical testing.
AB - OBJECTIVE: To examine the performance of screening for trisomies 21, 18 and 13 at
11-13 weeks' gestation using specific algorithms for these trisomies based on
combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR),
ductus venosus pulsatility index for veins (DV PIV), and serum free beta-human
chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein A (PAPP
A), placental growth factor (PLGF) and alpha-fetoprotein (AFP). METHODS: Model
based estimates of screening performance were produced for the distribution of
maternal ages in England and Wales in 2011, and prospectively collected data on
fetal NT, FHR, DV PIV, beta-hCG, PAPP-A, PLGF and AFP from singleton pregnancies
undergoing aneuploidy screening. RESULTS: In screening by NT, FHR, free beta-hCG
and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at
the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy
21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%.
Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and
95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. CONCLUSIONS: Effective
screening for trisomies can be achieved using specific algorithms based on NT,
FHR, DV PIV, beta-hCG, PAPP-A, PLGF and AFP.
PMID- 24356463
TI - Analysis of facial skin-resident microbiota in Japanese acne patients.
AB - OBJECTIVES: We investigated the facial skin microbiota of Japanese acne patients.
METHODS: Skin swab samples were obtained from 100 acne patients and 28 healthy
controls to evaluate Propionibacterium and Staphylococcus spp. using a culture
method. Malassezia spp. were evaluated using a nonculture method. Antibiotic
resistance of Propionibacterium spp. was also examined. RESULTS: Acne patients
and controls did not show significant differences in Propionibacterium and
Staphylococcus spp. populations. However, the number of Malassezia globosa from
patients was greater than that from controls. Moreover, the number of
Propionibacterium spp. from patients carrying antibiotic-resistant strains was
significantly greater than that from patients not carrying them. CONCLUSIONS: The
present study characterized the facial skin microbiota of Japanese acne patients,
suggesting a correlation between acne and quantitative differences in Malassezia
microbiota. It was also found that the antibiotic resistance of Propionibacterium
spp. may affect its abundance in the skin.
PMID- 24356464
TI - Measuring life space in older adults with mild-to-moderate Alzheimer's disease
using mobile phone GPS.
AB - BACKGROUND: As an indicator of physical and cognitive functioning in community
dwelling older adults, there is increasing interest in measuring life space,
defined as the geographical area a person covers in daily life. Typically
measured through questionnaires, life space can be challenging to assess in
amnestic dementia associated with Alzheimer's disease (AD). While global
positioning system (GPS) technology has been suggested as a potential solution,
there remains a lack of data validating GPS-based methods to measure life space
in cognitively impaired populations. OBJECTIVE: The purpose of the study was to
evaluate the construct validity of a GPS system to provide quantitative
measurements of global movement for individuals with mild-to-moderate AD.
METHODS: Nineteen community-dwelling older adults with mild-to-moderate AD (Mini
Mental State Examination score 14-28, age 70.7 +/- 2.2 years) and 33 controls
(CTL; age 74.0 +/- 1.2 years) wore a GPS-enabled mobile phone during the day for
3 days. Measures of geographical territory (area, perimeter, mean distance from
home, and time away from home) were calculated from the GPS log. Following a log
transformation to produce symmetrical distributions, group differences were
tested using two-sample t tests. Construct validity of the GPS measures was
tested by examining the correlation between the GPS measures and indicators of
physical function [steps/day, gait velocity, and Disability Assessment for
Dementia (DAD)] and affective state (Apathy Evaluation Scale and Geriatric
Depression Scale). Multivariate regression was performed to evaluate the relative
strength of significantly correlated factors. RESULTS: GPS-derived area (p <
0.01), perimeter (p < 0.01), and mean distance from home (p < 0.05) were smaller
in the AD group compared to CTL. The correlation analysis found significant
associations of the GPS measures area and perimeter with all measures of physical
function (steps/day, DAD, and gait velocity; p < 0.01), symptoms of apathy (p <
0.01), and depression (p < 0.05). Multivariate regression analysis indicated that
gait velocity and dependence were the strongest variables associated with GPS
measures. CONCLUSION: This study demonstrated that GPS-derived area and
perimeter: (1) distinguished mild-to-moderate AD patients from CTL and (2) were
strongly correlated with physical function and affective state. These findings
confirm the ability of GPS technology to assess life space behaviour and may be
particularly valuable to continuously monitor functional decline associated with
neurodegenerative disease, such as AD.
PMID- 24356465
TI - Structural, magnetic and electrical properties of one-dimensional
tetraamidatodiruthenium compounds.
AB - The first bromo and iodo tetraamidatodiruthenium compounds of the type [Ru2X(MU
NHOCC6H4-R)4]n [X = Br, R = o-Me (1), m-Me (2), p-Me (3); X = I, R = o-Me (4), m
Me (5), p-Me (6)] have been prepared using solvothermal or microwave activation
procedures. In these reactions ethanol or methanol as solvents have been used to
make the synthesis procedures more environment-friendly. Solvothermal synthesis
has allowed us to isolate single crystals of these extremely insoluble compounds
and the crystal structures of all of them have been determined using single
crystal X-ray diffraction. The change of the bridging halide ligand permits us to
discuss the properties of these complexes on the basis of their structure.
Complex 1 shows a Ru-Br-Ru angle of 180.0 degrees whereas in complexes 2-6 the
Ru-X-Ru angle varies from 110.16(2) to 115.39(4) degrees . In all compounds the
ruthenium atom has a cis-RuN2O2 environment except in compound 1 that shows a
positional disorder of N and O atoms. The bromide complex 1 shows a linear
arrangement of the paddlewheel units in the resulting 1D coordination polymer.
The fit of the magnetic data indicates that these compounds have non-negligible
values of zero-field splitting with D values ranging from 41.10 to 60.10 cm(-1)
and antiferromagnetic coupling constants from 0.00 to -4.13 cm(-1). Compound 1 is
the first linear paddlewheel diruthenium compound that does not show a maximum in
the representation of the magnetic susceptibility towards temperature. The
electrical conductivity measurements in the temperature range 300-400 K of
compounds 1, 4 and [Ru2Cl(MU-NHOCC6H4-o-Me)4]n (7) show that these compounds
present semiconducting behaviours with conductivity values at 400 K in the range
0.3-3.0 * 10(-8) S cm(-1) for the Cl derivative (7), 7-18 * 10(-8) S cm(-1) for
the Br derivative (1) and 27-68 * 10(-8) S cm(-1) for the I derivative (4) with
average values of 1.4 * 10(-8), 13 * 10(-8) and 47 * 10(-8) S cm(-1),
respectively.
PMID- 24356466
TI - GSK-3beta inhibition attenuates LPS-induced death but aggravates radiation
induced death via down-regulation of IL-6.
AB - BACKGROUND: Exposure of high dose ionizing radiation is lethal. Signal pathways
involved in radiation biology reaction still remain illdefined.
Lipopolysaccharides (LPS), the ligands of Toll-like receptor 4(TLR4), could
elicit strong immune responses. Glycogen synthase kinase-3beta(GSK-3beta)
promotes the production of inflammatory molecules and cell migration. Inhibition
of GSK-3beta provides protection against inflammation in animal models. The aim
of the study was to investigate role of GSK-3beta in LPS shock and ionizing
radiation. METHODS: WT or IL-6(-/-)mice or cells were pretreated with SB216763, a
GSK-3beta inhibitor, and survival of the mice was determined. Cell viability was
assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double
staining. Serum concentrations of IL-6 and TNF-alpha were determined by ELISA.
RESULTS: SB216763 attenuated LPS induced mice or cell death but aggravated
radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-alpha
levels in vivo. IL-6(-/-) mice were more resistant to LPS-induced death but less
resistant to radiation-induced death than wild type mice. CONCLUSIONS: Inhibition
of GSK-3beta conferred resistance to LPS shock but fostered death induced by
ionizing radiation. Inhibition of GSK-3beta was effective by reducing IL-6.
PMID- 24356467
TI - Unveiling the gating mechanism of ECF transporter RibU.
AB - Energy-coupling factor (ECF) transporters are responsible for uptake of
micronutrients in prokaryotes. The recently reported crystal structure of an ECF
transporter RibU provided a foundation for understanding the structure and
transport mechanism of ECF transporters. In the present study, molecular dynamics
(MD) was carried out to study the conformational changes of the S component RibU
upon binding by riboflavin. Our result and analysis revealed a critically
important gating mechanism, in which part of loop5 (L5') (eleven residues,
missing in the crystal structure) between TM5 and TM6 is dynamically flexible and
serves as a gate. Specifically, the L5' opens a large cavity accessible to
riboflavin from the extracellular space in Apo-RibU and closes the cavity upon
riboflavin binding through hydrophobic packing with riboflavin. Thus, L5'is
proposed to be the gate for riboflavin binding. In addition, steered molecular
dynamics (SMD) simulation is employed to investigate the translocation dynamics
of RibU during riboflavin transport. The simulation result does not show evidence
that the S component alone can carry out the transport function. Since loop
regions are very flexible and therefore could not be resolved by crystallography,
their dynamics are hard to predict based on crystal structure alone.
PMID- 24356470
TI - Carbon nanotube network film directly grown on carbon cloth for high-performance
solid-state flexible supercapacitors.
AB - Carbon nanotubes (CNTs) have received increasing attention as electrode materials
for high-performance supercapacitors. We herein present a straightforward method
to synthesize CNT films directly on carbon cloths as electrodes for all-solid
state flexible supercapacitors (AFSCs). The as-made highly conductive electrodes
possess a three-dimensional (3D) network architecture for fast ion diffusion and
good flexibility, leading to an AFSC with a specific capacitance of 106.1 F g-1,
an areal capacitance of 38.75 mF cm-2, an ultralong cycle life of 100,000 times
(capacitance retention: 99%), a good rate capability (can scan at 1000 mV s-1, at
which the capacitance is still ~37.8% of that at 5 mV s-1), a high energy density
(2.4 MUW h cm-2) and a high power density (19 mW cm-2). Moreover, our AFSC
maintains excellent electrochemical attributes even with serious shape
deformation (bending, folding, etc), high mechanical pressure (63 kPa) and a wide
temperature window (up to 100 degrees C). After charging for only 5 s, three
such AFSC devices connected in series can efficiently power a red round LED for
60 s. Our work could pave the way for the design of practical AFSCs, which are
expected to be used for various flexible portable/wearable electronic devices in
the future.
PMID- 24356469
TI - Comparison of the interleukin-1beta-inducing potency of allergenic spores from
higher fungi (basidiomycetes) in a cryopreserved human whole blood system.
AB - BACKGROUND: Spores from basidiomycete fungi (basidiospores) are highly prevalent
in the atmosphere of urban and rural settings. Studies have confirmed their
potential to affect human health as allergens. Less is known about their
potential to serve as stimuli of the innate immune system and induce
proinflammatory reactions. METHODS: In this study, we evaluated the
proinflammatory potential of spores from 11 allergenic basidiomycete species
(gilled: Pleurotus ostreatus,Oudemansiella radicata,Armillaria tabescens,Coprinus
micaceus,Pluteus cervinus, and Chlorophyllum molybdites, and nongilled:
Pisolithus arhizus,Merulius tremellosus,Calvatia cyathiformis,Lycoperdon
pyriforme, andBoletus bicolor) based on their potency to induce the release of
the proinflammatory cytokine interleukin (IL)-1beta in a cryopreserved human
whole blood system. In addition, the roles of morphological features of the
spores (surface area, shape, and pigmentation) were examined for their role in
the IL-1beta-including potency of spores. Peripheral blood from healthy
volunteers was collected, pooled, and cryopreserved. After stimulating the
cryopreserved pooled blood with 10(6) to 10(3) basidiospores/ml, the
concentration of IL-1beta in culture supernatants was determined with ELISA.
RESULTS: Basidiospores manifested concentration-dependent IL-1beta-inducing
potency, which was more marked among basidiospores from gilled basidiomycetes. At
higher concentrations of basidiospores, the IL-1beta-inducing potency could be
differentiated in the cryopreserved human whole blood system. Morphological
features did not correlate with the IL-1beta-inducing potency of the
basidiospores, suggesting that nonmorphological properties modulate the IL-1beta
inducing potency. CONCLUSION: Our data provide evidence of the proinflammatory
potential of basidiospores, and the utility of cryopreserved human whole blood as
a human-based in vitro system to study the immune reactivity of allergenic
basidiospores.
PMID- 24356468
TI - Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase.
AB - One of the hallmarks of cancers is the silencing of tumour suppressor genes and
pathways. The Hippo tumour suppressor pathway is inactivated in many types of
cancers, leading to tumour progression and metastasis. However, the mechanisms of
pathway inactivation in tumours remain unclear. Here we demonstrate that integrin
linked kinase (ILK) plays a critical role in the suppression of the Hippo pathway
via phospho-inhibition of MYPT1-PP1, leading to inactivation of Merlin.
Inhibition of ILK in breast, prostate and colon tumour cells results in the
activation of the Hippo pathway components MST1 and LATS1 with concomitant
inactivation of YAP/TAZ (Yes-associated protein/transcriptional co-activator with
PDZ-binding motif) transcriptional co-activators and TEAD-mediated transcription.
Genetic deletion of ILK suppresses ErbB2-driven YAP/TAZ activation in mammary
tumours, and its pharmacological inhibition suppresses YAP activation and tumour
growth in vivo. Our data demonstrate a role for ILK as a multiple receptor
proximal regulator of Hippo tumour suppressor pathway and as a cancer therapeutic
target.
PMID- 24356471
TI - Monitoring the obesity epidemic into the 21st century--weighing the evidence.
PMID- 24356473
TI - Ultrasound nail imaging on patients with psoriasis and psoriatic arthritis
compared with rheumatoid arthritis and control subjects.
AB - OBJECTIVE: The objective of this study was too show findings at finger nails
level revealed by high-frequency gray-scale ultrasound (US) and power Doppler in
patients with psoriatic arthritis (PsA),and cutaneous psoriasis compared with
rheumatoid arthritis and control subjects. METHODS: We studied 35 patients with
PsA, 20 with cutaneous psoriasis, and control groups (28 control subjects and 27
patients with rheumatoid arthritis). All nails of both hands were observed (1097
nails, 3 excluded because of trauma). In every patient, we classified the
morphologic abnormalities disclosed in ventral and dorsal nail plates. We also
measured the distance between ventral plate and the bone margin of the distal
phalanx at the right index finger. RESULTS: All patients and control subjects
presented abnormalities in the US imaging. Those with psoriatic arthritis and
cutaneous psoriasis showed a higher number of compromised nails. When classifying
those abnormalities using the typology of Wortsman et al, patients with psoriatic
arthritis showed loosening of the borders of the ventral plate (type II), whereas
patients with cutaneous psoriasis showed focal hyperechoic involvement of the
ventral plate without involvement of the dorsal plate (type I). Patients of the
control group could not be classified, although 31 of 55 showed thinning of the
ventral plate without hyperechoic deposits. Nineteen of 35 patients with
psoriatic arthritis, and 10 of 20 patients with cutaneous psoriasis did not show
any nail clinical alterations. Nevertheless, the US detected type II alterations
in the first group and type I in the second group. Patients with psoriatic
arthropathy had power Doppler increases in distal interphalangeal joints and nail
beds in a statistically significant form (P = 0.0001).When measuring the distance
between the ventral plate and the bone margin of the distal phalanx, there was
homogeneity among samples in patients and control subjects. A receiver operating
characteristic curve analysis determined that a cut point of 2 mm clearly defined
these 2 groups. There was a significant difference (P < 0.0001) between the mean
distance ventral plate-osseous margin of the distal phalanx in psoriatic
arthritis patients (P = 0.001) and patients with cutaneous psoriasis (P = 0.005)
versus rheumatoid arthritis patients (P = 0.548). CONCLUSIONS: As a predominant
finding in our study, we observed abnormalities of the ventral plate in patients
with PsA (type II) and abnormalities (type I) in patients with cutaneous
psoriasis. We found a significant difference between the mean distance ventral
plate-osseous margin of the distal phalanx in patients with PsA and patients with
cutaneous psoriasis versus control subjects. Ultrasound imaging could be a
feasible and sensitive tool to describe, measure, and follow morphologic
characteristics and changes of the nail in psoriatic and/ or psoriatic arthritis
patients with or without clinical nail lesions.
PMID- 24356474
TI - Open-label observation of addition of etanercept versus a conventional disease
modifying antirheumatic drug in subjects with active rheumatoid arthritis despite
methotrexate therapy in the Latin American region.
AB - BACKGROUND: Previous global studies examined etanercept (ETN) + methotrexate
(MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from
Latin America. OBJECTIVE: The objective of this study was to compare the safety
and efficacy of ETN + MTX versus a standard-of-care disease-modifying
antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to
severe active RA despite MTX therapy. METHODS: This open-label, active-comparator
study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator
selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281;
DMARD + MTX, n = 142). The primary end point was the proportion achieving
American College of Rheumatology (ACR) 50 at week 24. Secondary end points
included ACR20/70, disease activity score (DAS) 28 measures, and mean change in
modified total Sharp score. Patient-reported outcomes were the Health Assessment
Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work
Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and
Resource Utilization. Statistical analyses were stratified by country; chi test
and analysis of covariance were used. Adverse events were monitored. RESULTS:
More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs
23%, respectively), in addition to secondary end points (P < 0.0001 for all);
mean change in modified total Sharp score was lower for the ETN + MTX group (0.4
vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes
favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form,
Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver
Burden and Resource Utilization emergency department visits for RA (P < 0.01).
Overall, adverse events were similar between the groups (69% vs 68%,); serious
adverse events were also similar (4% vs 1%). The rate of overall infections was
higher with ETN + MTX (38%) than DMARD + MTX (22%, P <= 0.001). CONCLUSIONS:
Consistent with published global data among RA patients with inadequate response
to MTX, adding ETN to MTX demonstrated better efficacy than adding one other
conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided
favorable benefit-risk profile among RA patients from LA region.
PMID- 24356475
TI - Acute herpes simplex virus 1 pneumonitis in a patient with systemic lupus
erythematosus.
AB - A woman with severe and longstanding systemic lupus erythematosus presented with
a 1-week history of fever up to 38 degrees C and pain in her right flank.
Computed tomography scan of the chest revealed interstitial infiltrates and
multiple nodules. Bronchoalveolar lavage did not show any inflammatory cells.
Gram stain and cultures for aerobic and anaerobic bacteria, fungi, and Nocardia;
acid-fast staining; polymerase chain reaction for tuberculosis, cytomegalovirus,
herpesvirus 6, and parvovirus B19; and IF staining for pneumocystic and
Legionella antigen were all negative. Transbronchial biopsy was nondiagnostic.
Open lung biopsy with polymerase chain reaction and immunohistochemistry analyses
revealed herpes simplex virus 1 infection. Acyclovir therapy was initiated and
was followed by significant improvement. Herpes simplex virus 1 infection
(although unusual) should be considered in patients with systemic lupus
erythematosus with an atypical clinical presentation.
PMID- 24356476
TI - Critical hand ischemia caused by true arterial thoracic outlet syndrome.
PMID- 24356477
TI - Complex regional pain syndrome type I following tetanus toxoid injection.
PMID- 24356478
TI - Kimura disease complicated with bowel infarction and multiple arterial thromboses
in the extremities.
AB - Kimura disease (KD) is a chronic inflammatory disease characterized by slowly
growing subcutaneous nodules in the face and the neck region. Although a
concomitant hypercoagulable state can accompany KD, massive thromboses in
patients with KD have rarely been reported. Here, we report a case of KD
complicated with bowel infarction and multiple arterial thromboses in the upper
and lower extremities. The patient underwent bowel resection and was successfully
treated with corticosteroid and anticoagulation.
PMID- 24356479
TI - Cryofibrinogenemia triggered by a monoclonal paraprotein successfully treated
with cyclophosphamide.
AB - Cryofibrinogenemia is a rare clinical finding with a yet unknown physiopathogenic
mechanism. We describe the case of a woman with cold-induced extensive necrotic
lesions that responded poorly to initial corticosteroid and anticoagulant
therapies. Serum cryoglobulin determinations were persistently negative. After
several years of evolution, she developed severe cold-related skin lesions that
required left-leg amputation. Further analysis disclosed the presence of
cryofibrinogen and an apparently insignificant serum monoclonal immunoglobulin
Gkappa peak. We additionally demonstrate that the cold precipitation of
fibrinogen was directly related to the monoclonal paraprotein presence. The
lesions responded dramatically to a B cell-targeted therapy with intravenous
cyclophosphamide and dexamethasone.
PMID- 24356480
TI - Complementary and alternative medicine use in patients with gout: a longitudinal
observational study.
AB - BACKGROUND: Complementary and alternative medicine (CAM) is frequently used by
patients with arthritis. OBJECTIVES: The objectives of this study were to
determine the frequency and type of CAM used for gout, to understand the clinical
and psychological factors associated with CAM use in people with gout, and to
determine whether patients using CAM have different clinical outcomes over 1
year. METHODS: A total of 276 patients with gout for less than 10 years' duration
were recruited into a longitudinal observational study. Complementary and
alternative medicine information including frequency, type, and cost of therapies
were recorded at baseline. Gout disease activity (including flare frequency,
tophus count, Health Assessment Questionnaire II, and serum urate) was assessed
at baseline and after 1 year. RESULTS: Complementary and alternative medicine use
was reported by 23.9% of patients. A diverse range of CAM was used, most commonly
dietary supplements and vitamins. Patients using CAM reported higher levels of
concern about their gout but did not differ from those not taking CAM with
respect to age, sex, years of formal education, ethnicity, illness perceptions,
or gout disease activity measures at baseline or after 1 year. Total costs at
baseline related to gout therapy were higher in the CAM users compared with those
not using CAM (mean [SD] cost per month NZ $35.7 [NZ $69.0] vs NZ $7.1 [NZ
$22.8]; P = 0.001). CONCLUSIONS: Complementary and alternative medicine use is
not uncommon in patients with gout, albeit less than is reported in other
rheumatic diseases. Inquiry about CAM use should be incorporated into the
clinical assessment of patients with gout, to develop treatment plans that best
suit the individual patient's health beliefs.
PMID- 24356481
TI - Effect of golimumab on carotid atherosclerotic disease measures and
cardiovascular events in inflammatory arthritides.
AB - OBJECTIVE: The objective of this study was to assess the effect of golimumab on
carotid ultrasound measures and cardiovascular serious adverse events (SAEs) in
patients with inflammatory arthritides. METHODS: An exploratory carotid artery
ultrasound substudy was performed in the GO-BEFORE study of methotrexate (MTX)
naive rheumatoid arthritis patients, with ultrasounds performed at weeks 0, 24,
and 52 to measure common carotid artery intima-media thickness, distensibility
coefficient, interadventitial diameter, and plaque count. Cardiovascular SAEs
reported over 2 years of follow-up were assessed in 5 golimumab phase 3 clinical
trials of patients with rheumatoid arthritis (GO-BEFORE, GO-FORWARD, and GO
AFTER), psoriatic arthritis (GO-REVEAL), and ankylosing spondylitis (GO-RAISE).
In GO-BEFORE and GO-FORWARD, patients received placebo + MTX, golimumab 50 mg +
MTX, or golimumab 100 mg +/- MTX at baseline and every 4 weeks; in the other 3
trials, patients received placebo or golimumab 50 or 100 mg. RESULTS: The carotid
ultrasound substudy showed inconsistent changes in common carotid artery intima
media thickness in the golimumab + MTX groups over time, and there was large
variability in the measurements. Increases in interadventitial diameter were
observed in the golimumab 100 mg + placebo group, but not in the golimumab + MTX
groups. There were no significant differences in the distensibility coefficient
and plaque count between the golimumab and placebo groups. Very few patients
overall experienced a cardiovascular SAE, and the incidence of cardiovascular
SAEs was not statistically different between the golimumab and placebo groups.
CONCLUSIONS: The results of the carotid ultrasound substudy were inconclusive,
and no increase or decrease in cardiovascular SAEs was observed following 2 years
of treatment with golimumab with or without MTX.
PMID- 24356482
TI - Sustained remission of pediatric relapsing polychondritis with adalimumab.
PMID- 24356483
TI - Exercise as an adjuvant treatment in persistent active polymyositis.
AB - OBJECTIVES: A growing number of studies have suggested that exercise may promote
therapeutic effects in patients with idiopathic inflammatory myopathy. This
prospective case series study aimed to report on the effects of exercise in
patients with persistent active myositis. METHODS: Three patients with persistent
active polymyositis were submitted to a 12-week supervised exercise program
comprising both aerobic and strength exercises. RESULTS: After the intervention,
the patients presented improvements in selected parameters of muscle function and
aerobic conditioning. In addition, an overall improvement was detected in the
quality of life, as measured by both the 36-item Short-Form Health Survey and the
Health Assessment Questionnaire questionnaires. Importantly, exercise did not
increase serum levels of creatine kinase and aldolase. CONCLUSIONS: The findings
herein suggest that a combined aerobic and strength training program may be
tolerable and potentially effective in improving muscle function, aerobic
conditioning, and quality of life in patients with persistent active
polymyositis.
PMID- 24356484
TI - The utility of serum aldolase in normal creatine kinase dermatomyositis.
PMID- 24356485
TI - Tuberculous peritonitis in a patient with rheumatoid arthritis.
PMID- 24356486
TI - Use of herbal supplements with undeclared drug ingredients masking giant cell
arteritis.
PMID- 24356488
TI - Falling off the bandwagon? Exploring the challenges to sustained digital
engagement by older people.
AB - OBJECTIVES: This study examines older people's use of information and
communication technologies (ICTs) and identifies the factors which can prevent or
promote their sustained use. METHODS: A mixed methods approach was adopted.
Quantitative and qualitative data were collected by a survey of 323 older ICT
users (aged >=50 years) between 2011 and 2012. These data were supplemented by
qualitative data obtained through in-depth interviews, focus groups and
storytelling. Quantitative data were analysed using PASW including bivariate and
multivariate analyses. Qualitative data were analysed using an inductive,
thematic approach. RESULTS: The findings show that, contrary to some stereotypes,
many older people are enthusiastic, competent and confident users of ICTs.
However, they report a range of challenges in reaching and maintaining this
situation. These include technological complexity and change, age-related
capability changes and a lack of learning and support mechanisms. Intrinsic
motivation and social support are important in enabling older people to overcome
these challenges. DISCUSSION: Getting older people online has been a high
priority in many countries over the past decade. However, little attention has
been paid to whether and how their usage can be sustained over time. We discuss
the implications of the findings for policy and practice.
PMID- 24356489
TI - Up-regulated expression of miR-23a/b targeted the pro-apoptotic Fas in radiation
induced thymic lymphoma.
AB - BACKGROUND: MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs, which
usually bind to the 3'-untranslated region of target mRNAs and are capable of
inducing posttranscriptional gene regulation by blocking translation or by
degrading the target mRNA. However, the expression level of miR-23 in radiation
induced carcinogenesis is largely unknown. METHODS: Radiation induced thymic
lymphoma model in BALB/c mice was set up. miR-23a & miR-23b miRNA levels in
different tissues and cells were detected by real-time qPCR. miR-23a/b inhibitor
and miR-23a/b mimics were transfected to lymphoma cells and the target of miR
23a/b was identified by microRNA target prediction and Luciferase assays.
RESULTS: We found that miR-23a & miR-23b were up-regulated in radiation induced
thymic lymphoma tissue samples. Cell death and apoptosis were increased by miR
23a/b inhibitor and decreased by miR-23a/b mimics in lymphoma cells.
Computational analysis found a putative target site of miR-23a/b in the 3'UTR of
Fas mRNA, which was verified by luciferase reporter assay. Forced over-expression
of miR-23a/b decreased the level of Fas protein. Moreover, over-expression of Fas
rescued the pro-proliferation effect of miR-23, indicating Fas is a direct
mediator of miR-23 functions. Furthermore, contrast to miR-23a/b which was up
regulated, the Fas expression level was down-regulated and inversely correlated
with miR-23 in split radiation induced lymphoma tissue samples. Finally, our data
also indicates that miR-23a could repress Fas much more potent than miR-23b and
the additional region besides conserved seed pairing enables miR-23a's higher
regulation. CONCLUSIONS: In this study, using a radiation induced thymic lymphoma
model in BALB/c mice, We conclude that the expression of miR-23a/b is up
regulated in radiation-induced thymic lymphoma and it maybe a novel therapeutic
target of that cancer.
PMID- 24356490
TI - Appreciating David Barker (1938-2013).
PMID- 24356492
TI - The 'sparing phenomenon' of purpuric rash over tattooed skin.
AB - Cutaneous complications associated with decorative tattooing are well known.
However, the inhibition of a purpuric reaction by a tattoo is a fact that, as far
as the authors know, has not been described before, fitting the definition of a
'sparing phenomenon', the absence of manifesting a particular skin disease in an
area previously affected by another condition. From the clinical observation of
purpuric lesions apparently inhibited by a tattoo in a 26-year-old patient, we
performed an exact binomial test on the observed and expected proportion of
purpuric lesions inside (0%, 95% confidence interval, CI, 0-2.6%) and outside
(100%, 95% CI 97.4-100%) the tattooed skin, demonstrating a nonrandom
distribution respecting the tattooed area (p < 0.001) and identifying the
composition of the ink used in the tattoo (color pigment, glycerine, Hamamelis
virginiana extract, water and alcohol). Moreover, we reviewed the cases of
sparing phenomenon described in the literature. In conclusion this is the first
report of a sparing phenomenon of purpuric lesions over tattooed skin.
PMID- 24356493
TI - Vascular endothelial growth factor in acute lung injury and acute respiratory
distress syndrome.
AB - Acute respiratory distress syndrome (ARDS) is the most severe form of lung
injury, characterised by alveolar oedema and vascular permeability, in part due
to disruption of the alveolar capillary membrane integrity. Vascular endothelial
growth factor (VEGF) was originally identified as a vascular permeability factor
and has been implicated in the pathogenesis of acute lung injury/ARDS. This
review describes our current knowledge of VEGF biology and summarises the
literature investigating the potential role VEGF may play in normal lung
maintenance and in the development of lung injury.
PMID- 24356491
TI - RNA transport and long-term memory storage.
AB - Several studies have shown that synthesis of new proteins at the synapse is a
prerequisite for the storage of long-term memories. Relatively little is known
about the availability of distinct mRNA populations for translation at specific
synapses, the process that determines mRNA localization, and the temporal
designations of localized mRNA translation during memory storage. Techniques such
as synaptosome preparation and microdissection of distal neuronal processes of
cultured neurons and dendritic layers in brain slices are general approaches used
to identify localized RNAs. Exploration of the association of RNA-binding
proteins to the axonal transport machinery has led to the development of a
strategy to identify RNAs that are transported from the cell body to synapses by
molecular motor kinesin. In this article, RNA localization at the synapse, as
well as its mechanisms and significance in understanding long-term memory
storage, are discussed.
PMID- 24356494
TI - Understanding Masculinity in Undergraduate African American Men: A Qualitative
Study.
AB - This study reports findings on views of masculinity with undergraduate Black men,
which included interviews and focus groups (N = 46) with participants ranging in
age from 18 to 22 years. Specifically, this study explored how Black men define
being a man and being a Black man. Undergraduate Black males at a historically
Black college and university (N = 25) and a predominately White institution (N =
21) in the Southeastern United States were recruited to participate in this
study. Through the use of thematic analysis, findings indicated that three levels
of masculinity exist for Black men: what it means to be a man, what it means to
be a Black man, and who influences male development. Implications and
recommendations for future research and practice are discussed.
PMID- 24356495
TI - Patterns of Caribbean Masculinities and Condom Compliance Among Males in Grenada.
AB - The construction of Caribbean male identities based on ideas of masculinity has
raised widespread concerns across the island states, and in a region with such
high rates of teenage pregnancy (18%), stigmatizing safe sex, contraception, and
HIV/AIDS prevalence can only exacerbate the problem. The purpose of this study
was to examine the extent to which males use condoms and to explore the
association of condom use with their concern with acquiring and transmission of
sexually transmitted infections.
PMID- 24356496
TI - Principal component analysis of the Norwegian version of the quality of life in
late-stage dementia scale.
AB - AIMS: To investigate which factors the Quality of Life in Late-Stage Dementia
(QUALID) scale holds when used among people with dementia (pwd) in nursing homes
and to find out how the symptom load varies across the different severity levels
of dementia. METHODS: We included 661 pwd [mean age +/- SD, 85.3 +/- 8.6 years;
71.4% women]. The QUALID and the Clinical Dementia Rating (CDR) scale were
applied. A principal component analysis (PCA) with varimax rotation and Kaiser
normalization was applied to test the factor structure. Nonparametric analyses
were applied to examine differences of symptom load across the three CDR groups.
RESULTS: The mean QUALID score was 21.5 (+/-7.1), and the CDR scores of the three
groups were 1 in 22.5%, 2 in 33.6% and 3 in 43.9%. The results of the statistical
measures employed were the following: Crohnbach's alpha of QUALID, 0.74;
Bartlett's test of sphericity, p <0.001; the Kaiser-Meyer-Olkin measure, 0.77.
The PCA analysis resulted in three components accounting for 53% of the variance.
The first component was 'tension' ('facial expression of discomfort', 'appears
physically uncomfortable', 'verbalization suggests discomfort', 'being irritable
and aggressive', 'appears calm', Crohnbach's alpha = 0.69), the second was 'well
being' ('smiles', 'enjoys eating', 'enjoys touching/being touched', 'enjoys
social interaction', Crohnbach's alpha = 0.62) and the third was 'sadness'
('appears sad', 'cries', 'facial expression of discomfort', Crohnbach's alpha
0.65). The mean score on the components 'tension' and 'well-being' increased
significantly with increasing severity levels of dementia. CONCLUSION: Three
components of quality of life (qol) were identified. Qol decreased with
increasing severity of dementia.
PMID- 24356497
TI - Associations between adult attachment style, emotion regulation, and preschool
children's food consumption.
AB - OBJECTIVE: The goal of this study was to test 3 serial mediation models of how
caregiver adult attachment style influences children's food consumption through
its influence on emotion regulation. Three mediators that have been shown to
increase the risk for pediatric obesity and that are likely to be influenced by
negative emotion regulation strategies in everyday family interactions were
chosen: (1) caregiver feeding practices (2) family mealtime routines, and (3)
child television (TV) viewing. METHOD: A total of 497 primary caregivers of 2.5-
to 3.5-year-old children reported on their own attachment style, typical
responses to their children's negative affect, feeding styles, mealtime and TV
viewing routines, and their children's consumption of healthful and unhealthful
foods. RESULTS: Insecure mothers were more likely to use punishing or dismissing
responses to their children's negative affect, and negative emotion regulation
predicted the increased use of emotion-related feeding styles and fewer mealtime
routines. These variables, in turn, were found to predict children's unhealthful
food consumption, documenting serial mediational influences. With respect to TV
viewing, caregiver insecurity influenced child food consumption indirectly
through its direct effect on child TV viewing. CONCLUSION: Taken together, these
data suggest that insecure attachment may put parents at a risk for using
negative emotion regulation strategies in response to their children's distress,
which may also have important implications for the interpersonal environment
surrounding food and the development of children's early eating behaviors.
PMID- 24356498
TI - Disparities in Canadian indigenous health research on neurodevelopmental
disorders.
AB - OBJECTIVE: To map the landscape of research on autism (ASD), cerebral palsy (CP),
and fetal alcohol spectrum disorder (FASD) in Canadian Aboriginal children.
METHOD: The authors used a detailed search strategy to identify and access
publications on ASD, CP, and FASD involving Canadian Aboriginal children,
families, and communities from online databases. They analyzed these materials
for the type of research, stated objectives, methodologies, and the level of
engagement of Aboriginal Peoples. RESULTS: The authors found a total of 52
reports published since 1981 relevant to Aboriginal children. Of these, 51
focused exclusively on FASD. They also found a near-complete failure to
acknowledge community involvement in research decisions or dissemination of
results in any of the publications. CONCLUSIONS: The focus on FASD in Aboriginal
children and the absence of research on the other 2 major childhood disorders are
at odds with rates of these disorders across Canadian children. The authors argue
that this trend violates fundamental principles ensuring equitable representation
of all children regardless of background in research and access to benefits of
research in health care and perpetuates stigma in an already marginalized
population.
PMID- 24356499
TI - A direct anchoring of Anderson-type polyoxometalates in aqueous media with
tripodal ligands especially containing the carboxyl group.
AB - Polyoxometalate-based organic-inorganic hybrids were synthesized by direct
modification of the parent Anderson cluster with both the traditional tripodal
ligand, CH3C(CH2OH)3, and a novel one containing a carboxyl group,
CH3C(CH2OH)2(COOH), which was inaccessible from the traditional self-assembly
protocol.
PMID- 24356500
TI - Caring for frail older people: are we ready for the challenge?
PMID- 24356501
TI - Feedback from African palliative care practitioners on the use of the APCA POS.
PMID- 24356502
TI - Achieving effective control in cancer pain: a review of current guidelines.
AB - Pain is one of the most common and distressing elements of suffering related to
cancer and cancer treatment. Progress in cancer treatment means people will live
longer with the sequelae of cancer and disease-directed treatments, and both the
short- and long-term effects of opioid use must be considered. Skilled
practitioners caring for individuals with cancer help to alleviate cancer-related
pain by using the World Health Organization (WHO) step-wise approach to pain
management as well as recently updated national and international guidelines.
Current guidelines go beyond the unidimensional WHO model by addressing
comprehensive assessment, pharmacological management of opioids and adverse
effects associated with opioid use, the role of adjuvants, and the application of
non-pharmacological treatments. By following current guidelines promoting a
multifaceted approach to the management of cancer-related pain and advocating for
patient-centered care, nurses are uniquely positioned to champion effective
cancer pain management.
PMID- 24356503
TI - Nurses' experiences caring for patients and families dealing with malignant bowel
obstruction.
AB - Malignant bowel obstruction (MBO) is a well-recognised complication of advanced
abdominal and pelvic cancers. Often surgical intervention is not feasible,
resulting in complex symptoms and an unpredictable course. Although symptom
management is a crucial part of nursing care, psychosocial and emotional issues
frequently emerge for patients and families. This qualitative study explored the
perspectives of nurses from a palliative care unit, in-patient acute care
oncology units, ambulatory cancer setting, and the community on their experiences
of caring for patients with MBO and their families. Six individual interviews and
two focus groups were conducted. Eight overarching messages were identified
related to nurses' experiences. Highlights include aspects of patients' and
families' emotional distress, and the nurse-patient relationship in relieving
suffering. Nurses have an important and privileged role that involves identifying
MBO signs and symptoms, having knowledge of treatment and symptom management
options, and helping patients transition from a curative to a palliative
philosophy of care.
PMID- 24356504
TI - Spiritual support interventions in nursing care for patients suffering death
anxiety in the final phase of life.
AB - PURPOSE: To investigate which activities from the 'Spiritual Support'
intervention of the Nursing Interventions Classification (NIC) are used in
patients with the nursing diagnosis 'Death Anxiety' in the Czech Republic, and
which activities could feasibly be implemented into practice. METHOD: The study
surveyed 468 Czech nurses using a quantitative questionnaire with Likert scales.
RESULTS: The most frequently used activity was 'Treat individual with dignity and
respect' and the least frequently used was 'Pray with the individual'. 'Treat
individual with dignity and respect' was also thought to be the most feasible
activity for Czech nursing practice. Significant differences were found between
nurses working in hospices and those in other sites and between religious
believers and non-believers. CONCLUSION: Even in the secularised Czech Republic,
nurses can make use of the NIC Spiritual Support intervention in end-of-life
care.
PMID- 24356505
TI - Care managers' views on death and caring for older cancer patients in Japan.
AB - Care managers (CMs) have an important role in coordinating care for cancer
patients who are in the end-of-life stage; however, little is known about their
views of death and their experiences while caring for older cancer patients. This
study was conducted to examine CMs' views of death and caring for older cancer
patients in a home care setting in Japan. Convenience sampling was undertaken,
and 35 offices from 43 approached services agreed to participate. The final valid
sample included responses from 136 CMs (90.7%). Most CMs, including nurses, care
workers, home helpers, and social workers in home care settings, experienced
difficulty in managing the care of cancer patients in the end-of-life stage.
Respondents reported a wide array of experiences with end-of-life care, care
management, and seminar attendance, and their ages and Frommelt Attitude Toward
Care of the Dying (FATCOD) scores were associated factors. Moreover, multiple
regression analysis indicated that better attitudes toward caring for the dying
were positively associated with seminar attendance. These results suggest that
CMs need education about palliative and end-of-life care in order to promote good
home care for cancer patients.
PMID- 24356506
TI - The development of a 7-day community specialist palliative care service.
AB - The author worked as a clinical nurse specialist (CNS) in community palliative
care in the Central Lancashire area of England when the CNS service was extended
to a 9am-to-5pm 7-day service. A project group was set up to canvas some of the
key stakeholders for their views on the extension of the service. The group
undertook a literature search, a telephone survey of services in other areas that
were providing this level of service, and interviews to ascertain the views of
district nurses in the locality of the proposed service extension. The extension
of service has long been advocated and was one of the key recommendations in the
UK Department of Health's peer-review process. Such an extension was implemented
following the research phase and was then evaluated by the project lead and the
community services manager. The extension was found to be effective in the
ongoing monitoring and support of patients. Anecdotally, the CNS team also felt
it had been proactive in preventing unnecessary hospital admissions, although
this specific aspect is difficult to quantify. This article looks at how the
service was developed, how it has evolved over time, and how it works today.
Consideration is also given to benefits and limitations.
PMID- 24356510
TI - Directed self-assembled crystalline oligomer domains on graphene and graphite.
AB - We observe the formation of thin films of fibre-like aggregates from the
prototypical organic semiconductor molecule para-hexaphenylene (p-6P) on graphite
thin flakes and on monolayer graphene. Using atomic force microscopy, scanning
electron microscopy, x-ray diffraction, polarized fluorescence microscopy, and
bireflectance microscopy, the molecular orientations on the surface are deduced
and correlated to both the morphology as well as to the high-symmetry directions
of the graphitic surface: the molecules align with their long axis at +/-11
degrees with respect to a high-symmetry direction. The results show that the
graphene surface can be used as a growth substrate to direct the self-assembly of
organic molecular thin films and nanofibres, both with and without lithographical
processing.
PMID- 24356509
TI - Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding
to specific motifs.
AB - Exosomes are released by most cells to the extracellular environment and are
involved in cell-to-cell communication. Exosomes contain specific repertoires of
mRNAs, microRNAs (miRNAs) and other non-coding RNAs that can be functionally
transferred to recipient cells. However, the mechanisms that control the specific
loading of RNA species into exosomes remain unknown. Here we describe sequence
motifs present in miRNAs that control their localization into exosomes. The
protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) specifically
binds exosomal miRNAs through the recognition of these motifs and controls their
loading into exosomes. Moreover, hnRNPA2B1 in exosomes is sumoylated, and
sumoylation controls the binding of hnRNPA2B1 to miRNAs. The loading of miRNAs
into exosomes can be modulated by mutagenesis of the identified motifs or changes
in hnRNPA2B1 expression levels. These findings identify hnRNPA2B1 as a key player
in miRNA sorting into exosomes and provide potential tools for the packaging of
selected regulatory RNAs into exosomes and their use in biomedical applications.
PMID- 24356511
TI - Wide range tuning of resonant frequency for a vortex core in a regular triangle
magnet.
AB - A magnetic vortex structure stabilized in a micron or nano-sized ferromagnetic
disk has a strong potential as a unit cell for spin-based nano-electronic devices
because of negligible magnetostatic interaction and superior thermal stability.
Moreover, various intriguing fundamental physics such as bloch point reversal and
symmetry breaking can be induced in the dynamical behaviors in the magnetic
vortex. The static and dynamic properties of the magnetic vortex can be tuned by
the disk dimension and/or the separation distance between the disks. However, to
realize these modifications, the preparations of other devices with different
sample geometries are required. Here, we experimentally demonstrate that, in a
regular-triangle Permalloy dot, the dynamic properties of a magnetic vortex are
greatly modified by the application of the in-plane magnetic field. The obtained
wide range tunability based on the asymmetric position dependence of the core
potential provides attractive performances in the microwave spintronic devices.
PMID- 24356512
TI - All of ARIA in one puff?
PMID- 24356513
TI - Human platelets express functional thymic stromal lymphopoietin receptors: a
potential role in platelet activation in acute coronary syndrome.
AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP) has been shown to be expressed in
various inflammatory tissues, such as human atherosclerotic plaques. Many types
of myeloid cells involved in atherosclerosis, including mast cells, lymphocytes,
dendritic cells and monocytes/macrophages, present TSLP receptors (TSLPR).
However, it is unknown whether platelets, which also play important roles in
atherothrombosis, express TSLPR. METHODS AND RESULTS: We applied flow cytometry
and western blotting to show that TSLPR was expressed on the surface of human
platelets. Following the addition of TSLP to platelets, the expression of CD62P,
CD63, PAC-1 and p-Akt as well as aggregation and ATP release were increased
significantly. A TSLPR antibody and a PI3K (phosphatidylinositol 3-kinase) enzyme
inhibitor (LY294002) significantly inhibited the platelet activation induced by
TSLP. The expression of TSLPR, CD62P and CD63 and the increment of the expression
of CD62P and CD63 induced by TSLP in the acute coronary syndrome (ACS) group were
markedly higher than those in the control group and the stable angina pectoris
(SAP) group. The expression and the increment of the expression of CD62P and CD63
induced by TSLP were positively correlated with the expression of TSLPR.
CONCLUSION: Human platelets express functional TSLPR, which can be activated by
TSLP to promote platelet activation. TSLP/TSLPR functions via activating the
PI3K/AKT pathway, and this signalling pathway may be one of the mechanisms
involved in thrombosis in ACS. In coronary disease patients, the determination of
TSLPR in platelets may help to identify the risk of ACS.
PMID- 24356514
TI - Availability of binaural cues for bilateral implant recipients and bimodal
listeners with and without preserved hearing in the implanted ear.
AB - The purpose of this study was to examine the availability of binaural cues for
adult, bilateral cochlear implant (CI) patients, bimodal patients and hearing
preservation patients using a multiple-baseline, observational study design.
Speech recognition was assessed using the Bamford-Kowal-Bench Speech-in-Noise
(BKB-SIN) test as well as the AzBio sentences [Spahr AJ, et al: Ear Hear
2012;33:112-117] presented in a multi-talker babble at a +5 dB signal-to-noise
ratio (SNR). Test conditions included speech at 0 degrees with noise presented
at 0 degrees (S0N0), 90 degrees (S0N90) and 270 degrees (S0N270). Estimates of
summation, head shadow (HS), squelch and spatial release from masking (SRM) were
calculated. Though nonwwe of the subject groups consistently showed access to
binaural cues, the hearing preservation patients exhibited a significant
correlation between summation and squelch whereas the bilateral and bimodal
participants did not. That is to say, the two effects associated with binaural
hearing - summation and squelch - were positively correlated only for the
listeners with bilateral acoustic hearing. This finding provides evidence for the
supposition that implant recipients with bilateral acoustic hearing have access
to binaural cues, which should, in theory, provide greater benefit in noisy
listening environments. It is likely, however, that the chosen test environment
negatively affected the outcomes. Specifically, the spatially separated noise
conditions directed noise toward the microphone (mic) port of the behind-the-ear
(BTE) hearing aid and implant processor. Thus, it is possible that in more
realistic listening environments for which the diffuse noise is not directed
toward the processor/hearing aid mic, hearing preservation patients have binaural
cues for improved speech understanding.
PMID- 24356515
TI - The effect of supine exercise on the distribution of regional pulmonary blood
flow measured using proton MRI.
AB - The Zone model of pulmonary perfusion predicts that exercise reduces perfusion
heterogeneity because increased vascular pressure redistributes flow to
gravitationally nondependent lung, and causes dilation and recruitment of blood
vessels. However, during exercise in animals, perfusion heterogeneity as measured
by the relative dispersion (RD, SD/mean) is not significantly decreased. We
evaluated the effect of exercise on pulmonary perfusion in six healthy supine
humans using magnetic resonance imaging (MRI). Data were acquired at rest, while
exercising (~27% of maximal oxygen consumption) using a MRI-compatible ergometer,
and in recovery. Images were acquired in most of the right lung in the sagittal
plane at functional residual capacity, using a 1.5-T MR scanner equipped with a
torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and
regional proton density using a fast multiecho gradient-echo sequence. Perfusion
images were corrected for coil-based signal heterogeneity, large conduit vessels
removed and quantified (in ml.min(-1).ml(-1)) (perfusion), and also normalized
for density and quantified (in ml.min(-1).g(-1)) (density-normalized perfusion,
DNP) accounting for tissue redistribution. DNP increased during exercise (11.1 +/
3.5 rest, 18.8 +/- 2.3 exercise, 13.2 +/- 2.2 recovery, ml.min(-1).g(-1), P <
0.0001), and the increase was largest in nondependent lung (110 +/- 61% increase
in nondependent, 63 +/- 35% in mid, 70 +/- 33% in dependent, P < 0.005). The RD
of perfusion decreased with exercise (0.93 +/- 0.21 rest, 0.73 +/- 0.13 exercise,
0.94 +/- 0.18 recovery, P < 0.005). The RD of DNP showed a similar trend (0.82 +/
0.14 rest, 0.75 +/- 0.09 exercise, 0.81 +/- 0.10 recovery, P = 0.13). In
conclusion, in contrast to animal studies, in supine humans, mild exercise
decreased perfusion heterogeneity, consistent with Zone model predictions.
PMID- 24356517
TI - It's about numbers, not pictures.
PMID- 24356516
TI - Right ventricular dysfunction in chronic thromboembolic obstruction of the
pulmonary artery: a pressure-volume study using the conductance catheter.
AB - Pressure-volume loops describe dynamic ventricular performance, relevant to
patients with and at risk of pulmonary hypertension. We used conductance catheter
derived pressure-volume loops to measure right ventricular (RV) mechanics in
patients with chronic thromboembolic pulmonary arterial obstruction at different
stages of pathological adaptation. Resting conductance catheterization was
performed in 24 patients: 10 with chronic thromboembolic pulmonary hypertension
(CTEPH), 7 with chronic thromboembolic disease without pulmonary hypertension
(CTED), and 7 controls. To assess the validity of conductance measurements, RV
volumes were compared in a subset of 8 patients with contemporaneous cardiac
magnetic resonance (CMR). Control, CTED, and CTEPH groups showed different
pressure-volume loop morphology, most notable during systolic ejection. Prolonged
diastolic relaxation was seen in patients with CTED and CTEPH [tau = 56.2 +/- 6.7
(controls) vs. 69.7 +/- 10.0 (CTED) vs. 67.9 +/- 6.2 ms (CTEPH), P = 0.02].
Control and CTED groups had lower afterload (Ea) and contractility (Ees) compared
with the CTEPH group (Ea = 0.30 +/- 0.10 vs. 0.52 +/- 0.24 vs. 1.92 +/- 0.70
mmHg/ml, respectively, P < 0.001) (Ees = 0.44 +/- 0.20 vs. 0.59 +/- 0.15 vs. 1.13
+/- 0.43 mmHg/ml, P < 0.01) with more efficient ventriculoarterial coupling
(Ees/Ea = 1.46 +/- 0.30 vs. 1.27 +/- 0.36 vs. 0.60 +/- 0.18, respectively, P <
0.001). Stroke volume assessed by CMR and conductance showed closest agreement
(mean bias +9 ml, 95% CI -1 to +19 ml) compared with end-diastolic volume (+48
ml, -16 to 111 ml) and end-systolic volume (+37 ml, -21 to 94 ml). RV conductance
catheterization detects novel alteration in pressure-volume loop morphology and
delayed RV relaxation in CTED, which distinguish this group from controls. The
observed agreement in stroke volume assessed by CMR and conductance suggests RV
mechanics are usefully measured by conductance catheter in chronic thromboembolic
obstruction.
PMID- 24356518
TI - Nitric oxide-mediated vasodilation increases blood flow during the early stages
of stress fracture healing.
AB - Despite the strong connection between angiogenesis and osteogenesis in skeletal
repair conditions such as fracture and distraction osteogenesis, little is known
about the vascular requirements for bone formation after repetitive mechanical
loading. Here, established protocols of damaging (stress fracture) and
nondamaging (physiological) forelimb loading in the adult rat were used to
stimulate either woven or lamellar bone formation, respectively. Positron
emission tomography was used to evaluate blood flow and fluoride kinetics at the
site of bone formation. In the group that received damaging mechanical loading
leading to woven bone formation (WBF), (15)O water (blood) flow rate was
significantly increased on day 0 and remained elevated 14 days after loading,
whereas (18)F fluoride uptake peaked 7 days after loading. In the group that
received nondamaging mechanical loading leading to lamellar bone formation (LBF),
(15)O water and (18)F fluoride flow rates in loaded limbs were not significantly
different from nonloaded limbs at any time point. The early increase in blood
flow rate after WBF loading was associated with local vasodilation. In addition,
Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs.
The nitric oxide (NO) synthase inhibitor N(omega)-nitro-l-arginine methyl ester
was used to suppress NO generation, resulting in significant decreases in early
blood flow rate and bone formation after WBF loading. These results demonstrate
that NO-mediated vasodilation is a key feature of the normal response to stress
fracture and precedes woven bone formation. Therefore, patients with impaired
vascular function may heal stress fractures more slowly than expected.
PMID- 24356520
TI - AltitudeOmics: enhanced cerebrovascular reactivity and ventilatory response to
CO2 with high-altitude acclimatization and reexposure.
AB - The present study is the first to examine the effect of high-altitude
acclimatization and reexposure on the responses of cerebral blood flow and
ventilation to CO2. We also compared the steady-state estimates of these
parameters during acclimatization with the modified rebreathing method. We
assessed changes in steady-state responses of middle cerebral artery velocity
(MCAv), cerebrovascular conductance index (CVCi), and ventilation (V(E)) to
varied levels of CO2 in 21 lowlanders (9 women; 21 +/- 1 years of age) at sea
level (SL), during initial exposure to 5,260 m (ALT1), after 16 days of
acclimatization (ALT16), and upon reexposure to altitude following either 7
(POST7) or 21 days (POST21) at low altitude (1,525 m). In the nonacclimatized
state (ALT1), MCAv and V(E) responses to CO2 were elevated compared with those at
SL (by 79 +/- 75% and 14.8 +/- 12.3 l/min, respectively; P = 0.004 and P =
0.011). Acclimatization at ALT16 further elevated both MCAv and Ve responses to
CO2 compared with ALT1 (by 89 +/- 70% and 48.3 +/- 32.0 l/min, respectively; P <
0.001). The acclimatization gained for V(E) responses to CO2 at ALT16 was
retained by 38% upon reexposure to altitude at POST7 (P = 0.004 vs. ALT1),
whereas no retention was observed for the MCAv responses (P > 0.05). We found
good agreement between steady-state and modified rebreathing estimates of MCAv
and V(E) responses to CO2 across all three time points (P < 0.001, pooled data).
Regardless of the method of assessment, altitude acclimatization elevates both
the cerebrovascular and ventilatory responsiveness to CO2. Our data further
demonstrate that this enhanced ventilatory CO2 response is partly retained after
7 days at low altitude.
PMID- 24356519
TI - Skeletal muscle morphology and contractile function in relation to muscle
denervation in diabetic neuropathy.
AB - The objective of the study was to assess the effects of diabetic polyneuropathy
(DPN) on muscle contractile properties in humans, and how these changes are
related to alterations in muscle morphology and denervation. Patients with DPN (n
= 12) were compared with age- and sex-matched controls (n = 12). Evoked and
voluntary contractile properties, including stimulated twitch responses and
maximal voluntary contractions, of the dorsiflexor muscles were assessed using an
isometric ankle dynamometer. Motor unit number estimates (MUNE) of the tibialis
anterior (TA) were performed via quantitative electromyography and decomposition
enhanced spike-triggered averaging. Peak tibialis anterior (TA) cross-sectional
area (CSA; cm(2)), and relative proportion of contractile to noncontractile
tissue (%) was determined from magnetic resonance images. Patients with DPN
demonstrated decreased strength (-35%) and slower (-45%) dorsiflexion contractile
properties for both evoked and voluntary contractions (P < 0.05). These findings
were not accounted for by differences in voluntary activation (P > 0.05) or
antagonist coactivation (P > 0.05). Additionally, patients with DPN were weaker
when strength was normalized to TA total CSA (-30%; P < 0.05) or contractile
tissue CSA (-26%; P < 0.05). In the DPN patient group, TA MUNEs were negatively
related to both % noncontractile tissue (P < 0.05; r = 0.72) and twitch half
relaxation time (P < 0.05; r = 0.60), whereas no relationships were found between
these variables in controls (P > 0.05). We conclude that patients with DPN
demonstrated reduced strength and muscle quality as well as contractile slowing.
This process may contribute to muscle power loss and functional impairments
reported in patients with DPN, beyond the loss of strength commonly observed.
PMID- 24356521
TI - The human upper airway: more than a floppy tube.
PMID- 24356522
TI - Fatigue-related firing of distal muscle nociceptors reduces voluntary activation
of proximal muscles of the same limb.
AB - With fatiguing exercise, firing of group III/IV muscle afferents reduces
voluntary activation and force of the exercised muscles. These afferents can also
act across agonist/antagonist pairs, reducing voluntary activation and force in
nonfatigued muscles. We hypothesized that maintained firing of group III/IV
muscle afferents after a fatiguing adductor pollicis (AP) contraction would
decrease voluntary activation and force of AP and ipsilateral elbow flexors. In
two experiments (n = 10) we examined voluntary activation of AP and elbow flexors
by measuring changes in superimposed twitches evoked by ulnar nerve stimulation
and transcranial magnetic stimulation of the motor cortex, respectively.
Inflation of a sphygmomanometer cuff after a 2-min AP maximal voluntary
contraction (MVC) blocked circulation of the hand for 2 min and maintained firing
of group III/IV muscle afferents. After a 2-min AP MVC, maximal AP voluntary
activation was lower with than without ischemia (56.2 +/- 17.7% vs. 76.3 +/-
14.6%; mean +/- SD; P < 0.05) as was force (40.3 +/- 12.8% vs. 57.1 +/- 13.8%
peak MVC; P < 0.05). Likewise, after a 2-min AP MVC, elbow flexion voluntary
activation was lower with than without ischemia (88.3 +/- 7.5% vs. 93.6 +/- 3.9%;
P < 0.05) as was torque (80.2 +/- 4.6% vs. 86.6 +/- 1.0% peak MVC; P < 0.05).
Pain during ischemia was reported as Moderate to Very Strong. Postfatigue firing
of group III/IV muscle afferents from the hand decreased voluntary drive and
force of AP. Moreover, this effect decreased voluntary drive and torque of
proximal unfatigued muscles, the elbow flexors. Fatigue-sensitive group III/IV
muscle nociceptors act to limit voluntary drive not only to fatigued muscles but
also to unfatigued muscles within the same limb.
PMID- 24356523
TI - Surfactant before the first inflation at birth improves spatial distribution of
ventilation and reduces lung injury in preterm lambs.
AB - The interrelationship between the role of surfactant and a sustained inflation
(SI) to aid ex utero transition of the preterm lung is unknown. We compared the
effect of surfactant administered before and after an initial SI on gas exchange,
lung mechanics, spatial distribution of ventilation, and lung injury in preterm
lambs. Gestational-age lambs (127 days; 9 per group) received 100 mg/kg of a
surfactant (Curosurf) either prior (Surf+SI) or 10 min after birth (SI+Surf). At
birth, a 20-s, 35 cmH2O SI was applied, followed by 70 min of positive pressure
ventilation. Oxygenation, carbon dioxide removal, respiratory system compliance,
end-expiratory thoracic volume (via respiratory inductive plethysmography), and
distribution of end-expiratory volume and ventilation (via electrical impedance
tomography) were measured throughout. Early markers of lung injury were analyzed
using quantitative RT-PCR. During the first 15 min, oxygenation, carbon dioxide
removal, and compliance were better in the Surf+SI group (all P < 0.05). End
expiratory volume on completion of the sustained inflation was higher in the
Surf+SI group than the SI+Surf group; 11 +/- 1 ml/kg vs. 7 +/- 1 ml/kg (mean +/-
SE) (P = 0.043; t-test), but was not different at later time points. Although
neither achieved homogenous aeration, spatial ventilation was more uniform in the
Surf+SI group throughout; 50.1 +/- 10.9% of total ventilation in the left
hemithorax at 70 min vs. 42.6 +/- 11.1% in the SI+Surf group. Surf+SI resulted in
lower mRNA levels of CYR61 and EGR1 compared with SI+Surf (P < 0.001, one-way
ANOVA). Surfactant status of the fetal preterm lung at birth influences the
mechanical and injury response to a sustained inflation and ventilation by
changing surface tension of the air/fluid interface.
PMID- 24356524
TI - Physiological mechanisms of dyspnea during exercise with external thoracic
restriction: role of increased neural respiratory drive.
AB - We tested the hypothesis that neuromechanical uncoupling of the respiratory
system forms the mechanistic basis of dyspnea during exercise in the setting of
"abnormal" restrictive constraints on ventilation (VE). To this end, we examined
the effect of chest wall strapping (CWS) sufficient to mimic a "mild" restrictive
lung deficit on the interrelationships between VE, breathing pattern, dynamic
operating lung volumes, esophageal electrode-balloon catheter-derived measures of
the diaphragm electromyogram (EMGdi) and the transdiaphragmatic pressure time
product (PTPdi), and sensory intensity and unpleasantness ratings of dyspnea
during exercise. Twenty healthy men aged 25.7 +/- 1.1 years (means +/- SE)
completed symptom-limited incremental cycle exercise tests under two randomized
conditions: unrestricted control and CWS to reduce vital capacity (VC) by 21.6 +/
0.5%. Compared with control, exercise with CWS was associated with 1) an
exaggerated EMGdi and PTPdi response; 2) no change in the relationship between
EMGdi and each of tidal volume (expressed as a percentage of VC), inspiratory
reserve volume, and PTPdi, thus indicating relative preservation of
neuromechanical coupling; 3) increased sensory intensity and unpleasantness
ratings of dyspnea; and 4) no change in the relationship between increasing EMGdi
and each of the intensity and unpleasantness of dyspnea. In conclusion, the
increased intensity and unpleasantness of dyspnea during exercise with CWS could
not be readily explained by increased neuromechanical uncoupling but likely
reflected the awareness of increased neural respiratory drive (EMGdi) needed to
achieve any given VE during exercise in the setting of "abnormal" restrictive
constraints on tidal volume expansion.
PMID- 24356526
TI - Prenatal prediction of surgical approach for coarctation of the aorta repair.
AB - OBJECTIVE: To evaluate the capacity of fetal echocardiography for predicting the
more likely surgical approach in newborns with coarctation of the aorta (CoAo)
(left thoracotomy vs. median sternotomy). MATERIAL AND METHODS: We selected all
cases of suspected CoAo prenatally diagnosed in 2003-2012 (n = 95). 49/95 were
considered at high-risk and 46/95 at low-risk of CoAo, and 38/49 and 7/46 were
postnatally confirmed, respectively. We firstly evaluated in 40 cases of CoAo
surgically repaired (24 thoracotomy, 16 sternotomy) whether there were
differences in fetal echocardiographic parameters between both groups. Secondly,
we assessed the performance of these parameters for predicting the surgical
approach in fetuses at high risk of CoAo. RESULTS: Sternotomy approach was
associated with higher rate of postoperative complications and longer hospital
stay compared with thoracotomy (81.3 vs. 41.7%, p = 0.014; 30.5 vs. 15.4 days, p
= 0.0004, respectively). The Z-score of the aortic isthmus, measured in the
sagittal plane, was significantly smaller in the sternotomy group. In fetuses at
high-risk of having CoAo a cut-off value of the isthmus Z-score <= -2.5 had
sensitivity of 78% and specificity of 82% for predicting sternotomy approach,
with 9% false positive cases in which CoAo was not confirmed. DISCUSSION: The
surgical approach for CoAo repair may be prenatally predicted by means of the Z
score of aortic isthmus, measured in the sagittal plane.
PMID- 24356525
TI - Validation of lower body negative pressure as an experimental model of
hemorrhage.
AB - Lower body negative pressure (LBNP), a model of hemorrhage (Hem), shifts blood to
the legs and elicits central hypovolemia. This study compared responses to LBNP
and actual Hem in sedated baboons. Arterial pressure, pulse pressure (PP),
central venous pressure (CVP), heart rate, stroke volume (SV), and +dP/dt were
measured. Hem steps were 6.25%, 12.5%, 18.75%, and 25% of total estimated blood
volume. Shed blood was returned, and 4 wk after Hem, the same animals were
subjected to four LBNP levels which elicited equivalent changes in PP and CVP
observed during Hem. Blood gases, hematocrit (Hct), hemoglobin (Hb), plasma renin
activity (PRA), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE)
were measured at baseline and maximum Hem or LBNP. LBNP levels matched with
6.25%, 12.5%, 18.75%, and 25% hemorrhage were -22 +/- 6, -41 +/- 7, -54 +/- 10,
and -71 +/- 7 mmHg, respectively (mean +/- SD). Hemodynamic responses to Hem and
LBNP were similar. SV decreased linearly such that 25% Hem and matching LBNP
caused a 50% reduction in SV. Hem caused a decrease in Hct, Hb, and central
venous oxygen saturation (ScvO2). In contrast, LBNP increased Hct and Hb, while
ScvO2 remained unchanged. Hem caused greater elevations in AVP and NE than LBNP,
while PRA, EPI, and other hematologic indexes did not differ between studies.
These results indicate that while LBNP does not elicit the same effect on blood
cell loss as Hem, LBNP mimics the integrative cardiovascular response to Hem, and
validates the use of LBNP as an experimental model of central hypovolemia
associated with Hem.
PMID- 24356527
TI - Functional, anatomical, and molecular investigation of the cardiac conduction
system and arrhythmogenic atrioventricular ring tissue in the rat heart.
AB - BACKGROUND: The cardiac conduction system consists of the sinus node, nodal
extensions, atrioventricular (AV) node, penetrating bundle, bundle branches, and
Purkinje fibers. Node-like AV ring tissue also exists at the AV junctions, and
the right and left rings unite at the retroaortic node. The study aims were to
(1) construct a 3-dimensional anatomical model of the AV rings and retroaortic
node, (2) map electrical activation in the right ring and study its action
potential characteristics, and (3) examine gene expression in the right ring and
retroaortic node. METHODS AND RESULTS: Three-dimensional reconstruction (based on
magnetic resonance imaging, histology, and immunohistochemistry) showed the
extent and organization of the specialized tissues (eg, how the AV rings form the
right and left nodal extensions into the AV node). Multiextracellular electrode
array and microelectrode mapping of isolated right ring preparations revealed
robust spontaneous activity with characteristic diastolic depolarization. Using
laser microdissection gene expression measured at the mRNA level (using
quantitative PCR) and protein level (using immunohistochemistry and Western
blotting) showed that the right ring and retroaortic node, like the sinus node
and AV node but, unlike ventricular muscle, had statistically significant higher
expression of key transcription factors (including Tbx3, Msx2, and Id2) and ion
channels (including HCN4, Cav3.1, Cav3.2, Kv1.5, SK1, Kir3.1, and Kir3.4) and
lower expression of other key ion channels (Nav1.5 and Kir2.1). CONCLUSIONS: The
AV rings and retroaortic node possess gene expression profiles similar to that of
the AV node. Ion channel expression and electrophysiological recordings show the
AV rings could act as ectopic pacemakers and a source of atrial tachycardia.
PMID- 24356528
TI - Perceived stress is associated with incident coronary heart disease and all-cause
mortality in low- but not high-income participants in the Reasons for Geographic
And Racial Differences in Stroke study.
AB - BACKGROUND: Perceived stress may increase risk for coronary heart disease (CHD)
and death, but few studies have examined these relationships longitudinally. We
sought to determine the association of perceived stress with incident CHD and all
cause mortality. METHODS AND RESULTS: Data were from a prospective study of 24
443 participants without CHD at baseline from the national Reasons for Geographic
And Racial Differences in Stroke (REGARDS) study cohort. Outcomes were expert
adjudicated acute CHD and all-cause mortality. Over a mean follow-up of 4.2
(maximum 6.9) years, there were 659 incident CHD events and 1320 deaths. Analyses
were stratified by income level because of significant interactions with stress.
For individuals with low income, 3529 (35.4%) reported high stress, and for those
with high income, 2524 (22.1%) did so. Compared with reporting no stress, those
reporting the highest stress had higher risk for incident CHD if they reported
low income (sociodemographic-adjusted HR 1.36, 95% CI: 1.04, 1.78) but not high
income (sociodemographic-adjusted HR 0.82, 95% CI: 0.57, 1.16); the finding in
low income individuals attenuated with adjustment for clinical and behavioral
factors (HR 1.29, 95% CI: 0.99, 1.69, P=0.06). After full adjustment, the highest
stress category was associated with higher risk for death among those with low
income (HR 1.55, 95% CI: 1.31, 1.82) but not high income (HR 1.13, 95% CI: 0.88,
1.46). CONCLUSIONS: High stress was associated with greater risks of CHD and
death for individuals with low but not high income.
PMID- 24356531
TI - Surveillance and Countermeasures in Innate Immunity.
PMID- 24356530
TI - Adolescent overweight, obesity and chronic disease-related health practices:
mediation by body image.
AB - BACKGROUND/AIMS: To examine whether body image mediates the association between
overweight/obesity and chronic disease-related health practices (CDRHP),
including lack of physical activity (PA), infrequent breakfast consumption (IBC),
screen-based media use (SBM), and smoking. METHODS: The 2006 Health Behaviors in
School-Age Children survey was administered to a nationally representative sample
of US students (n = 8,028) in grades 6-10 (mean age = 14.3 years). Outcome
variables included self-reported measures of PA, SBM, IBC, and smoking. Body
image was assessed with 5 items from the Body Investment Scale (alpha = 0.87)
asking for agreement/disagreement with statements about one's body. Stratifying
on gender, an initial regression model estimated the association between
overweight/obesity and CDRHP. Mediation models that included body image were then
compared to the initial model to determine the role of body image in the
relationship between overweight/obesity and CDRHP. RESULTS: Among boys, body
image mediated the relationships of overweight/obesity with SBM, and of obesity
with IBC. Among girls, it mediated the relationships of obesity with PA, IBC, and
smoking, and of overweight with SBM. CONCLUSION: As the prevalence of
overweight/obesity among adolescent boys and girls remains high, efforts to
improve their body image could result in less frequent engagement in CDRHP.
PMID- 24356532
TI - (enH2)(4.5)[In(As(V)S4)3][As2(III)(MU-S2)S3]Cl and (enH2)MnAs(III)As(V)S6: two
thioarsenates(III, V) with mixed-valent optical properties.
AB - Two mixed-valent thioarsenates, namely (enH2)(4.5)[In(As(V)S4)3][As2(III)(MU
S2)S3]Cl (1) and (enH2)MnAs(III)As(V)S6 (2) (en = ethylenediamine), have been
solvothermally synthesized and characterized. Thermal stability, magnetic and
mixed-valent optical properties, as well as theoretical band structures and DOSs,
of 1 and 2 have also been studied.
PMID- 24356534
TI - Nano-CdS confined within titanate nanotubes for efficient photocatalytic hydrogen
production under visible light illumination.
AB - CdS nanoparticles were confined within titanate nanotubes (TNTs) by an ion
exchange reaction and a subsequent sulfurization process. Prior to the ion
exchange reaction, the exterior surfaces of the TNTs were modified by a silane
coupling agent to make CdS nanoparticles selectively deposit on the inner wall.
The composites were characterized by high-resolution transmission electron
microscopy, powder x-ray diffraction, inductively coupled plasma atomic emission
spectrometry, N2 adsorption-desorption and UV-vis absorption spectra. The results
confirm that CdS in the range of 2-3 nm in diameter are confined within the inner
cavity of the TNTs. CdS confined within TNTs shows a significant blue-shift of
the absorption band edge compared with CdS nanoparticles deposited on the
exterior surface of TNTs. Also the TNTs-confined CdS composite exhibits enhanced
photocatalytic activity and photostability for hydrogen evolution under visible
light illumination due to the quantum size effect of CdS as a result of the
spatial confinement effect of the TNTs.
PMID- 24356533
TI - Implementing panel management for hypertension in a low-income, urban, primary
care setting.
AB - OBJECTIVE: Panel management is a system of care that targets groups of patients
with similar needs to improve their quality of care. The purpose of this pilot
was to determine whether panel management could improve blood pressure control in
patients with previously uncontrolled hypertension and to explore how panel
management can be integrated in an urban, low-income, primary care setting.
METHODS: The practice coach model was used to assist a clinical site in forming a
quality improvement team to implement panel management. The team created a
patient registry to track hypertensive patients over time and to recall patients
with uncontrolled hypertension for planned care visits during which evidence
based interventions for hypertension were delivered. Percent of patients gaining
control of blood pressure and change in blood pressure were measured between 6
and 9 months after enrollment. Qualitative interviews of clinic staff were
completed to explore strengths and weaknesses of program implementation. RESULTS:
Forty patients with uncontrolled hypertension were enrolled in the pilot, and
27.5% gained blood pressure control by 9 months after enrollment (P < .001). The
average systolic blood pressure decreased by 16 mm Hg from 156.5 to 140.5 mm Hg
(P < .001), and the average diastolic blood pressure decreased by 3.8 mm Hg from
85 to 81.2 mm Hg (P = .03). Staff interviews were generally positive; however,
several areas for improvement were identified. CONCLUSION: Panel management for
hypertension can be effective and can be implemented in a low-income, urban,
primary care clinic setting given appropriate staffing allocation.
PMID- 24356535
TI - Hierarchical nanocomposites of polyaniline nanowire arrays on reduced graphene
oxide sheets for supercapacitors.
AB - Here we reported a novel route to synthesize a hierarchical nanocomposite (PANI
frGO) of polyaniline (PANI) nanowire arrays covalently bonded on reduced graphene
oxide (rGO). In this strategy, nitrophenyl groups were initially grafted on rGO
via C-C bond, and then reduced to aminophenyl to act as anchor sites for the
growth of PANI arrays on rGO. The functionalized process was confirmed by atomic
force microscopy, scanning electron microscopy, Fourier transform infrared
spectroscopy, Raman spectroscopy and thermogravimetric analysis. The
electrochemical properties of the PANI-frGO as supercapacitor materials were
investigated. The PANI-frGO nanocomposites showed high capacitance of 590 F g(-1)
at 0.1 A g(-1), and had no loss of capacitance after 200 cycles at 2 A g(-1). The
improved electrochemical performance suggests promising application of the PANI
frGO nanocomposites in high-performance supercapacitors.
PMID- 24356536
TI - Dermoscopic rosettes as a clue for pigmented incipient melanoma.
AB - The rosette structure is a dermoscopic sign visible under polarized light,
characterized by 4 white points arranged as a 4-leaf clover. It has been mainly
described in facial sun-damaged skin and actinic keratosis, although it has also
been found in squamous and basal cell carcinomas, and in 2 cases of hypomelanotic
melanomas. We describe 2 different cases of pigmented incipient melanomas with
the presence of multiple rosettes and shiny white structures on dermoscopy. In
the reflectance confocal microscope they exhibit a disarranged epidermal
architecture with atypical and dendritic cells. Histological examination showed
focal hyperkeratosis and a normal corneal layer presented alternatively. To our
knowledge this is the first description of rosette structures in pigmented
melanomas. Based on a proper dermoscopic- confocal-histopathological correlation,
we hypothesize that rosettes could correspond to optic phenomena due to changes
in the superficial epidermal reaction and in the acrosyringia.
PMID- 24356537
TI - Early diagnosis of Alzheimer's disease and Parkinson's disease associated with
dementia using cerebral perfusion SPECT.
AB - BACKGROUND: Since patterns of cognitive dysfunction in mild Parkinson's disease
associated with dementia (PDD) are similar to those in mild Alzheimer's disease
(AD), it is difficult to accurately differentiate between these two types of
dementia in their early phases using neuropsychological tests. The purpose of the
current study was to investigate differences in cerebral perfusion patterns of
patients with AD and PDD at the earliest stages using single photon emission
computed tomography (SPECT). METHODS: We consecutively recruited 31 patients with
mild PDD, 32 patients with mild probable AD and 33 age-matched healthy subjects.
All subjects underwent (99m)Tc-hexamethylpropyleneamine oxime perfusion SPECT and
completed general neuropsychological tests. RESULTS: We found that both mild PDD
and AD patients showed distinct hypoperfusion in frontal, parietal and temporal
regions, compared with healthy subjects. More importantly, hypoperfusion in
occipital and cerebellar regions was observed only in mild PDD. CONCLUSION: The
observation of a significant decrease in cerebral perfusion in occipital and
cerebellar regions in patients with mild PDD is likely useful to differentiate
between PDD and AD at the earliest stages.
PMID- 24356539
TI - Osthole exhibits anti-cancer property in rat glioma cells through inhibiting
PI3K/Akt and MAPK signaling pathways.
AB - AIMS: The purpose of this study was to investigate how Osthole affects glioma
cell proliferation, apoptosis, invasion and migration. METHODS: Rat glioma cells
were treated with different concentrations of Osthole (0 uM, 25 uM, 50 uM, and
100 uM). Cell proliferation was assessed by measuring PCNA expression and CCK8
assay at different time points. Apoptosis was evaluated by measuring the
expression of pro-apoptotic protein including Bax, Bcl2, PARP, and cleaved
Caspase3, and of anti-apoptotic protein Survivin. Cell migration and invasion
were assessed using different methods. Signaling pathways such as PI3K/Akt and
MAPK, which are involved in the development of glioma cells, were also
investigated in this study. RESULTS: Treatment with Osthole markedly inhibits
glioma cell proliferation, as assessed by western blot with the PCNA antibody.
Osthole also induces cell apoptosis by upregulating the expression of pro
apoptotic proteins, and by reducing the expression of anti-apoptotic factors.
Moreover, C6 cell migration and invasion were efficiently inhibited in groups
treated with Osthole, compared to the control group. Additionally, inhibition of
PI3K/Akt and MAPK signaling pathway was also observed in C6 cells treated with
Osthole. CONCLUSIONS: Our findings showed an anti-cancer effect of Osthole on
glioma cells, including the proliferation inhibition, apoptosis induction, and
migration/invasion inhibition. Further investigation in C6 glioma cells
implicated the role of Osthole in essential pathways controlling glioma cell
progression. Taken together, our data suggested that Osthole may have a potential
application in glioma therapy.
PMID- 24356538
TI - Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation.
AB - Atopic asthma is an inflammatory pulmonary disease associated with Th2 adaptive
immune responses triggered by innocuous antigens. While dendritic cells (DCs) are
known to shape the adaptive immune response, the mechanisms by which DCs promote
Th2 differentiation remain elusive. Herein we demonstrate that Th2-promoting
stimuli induce DC expression of IRF4. Mice with conditional deletion of Irf4 in
DCs show a dramatic defect in Th2-type lung inflammation, yet retain the ability
to elicit pulmonary Th1 antiviral responses. Using loss- and gain-of-function
analysis, we demonstrate that Th2 differentiation is dependent on IRF4 expression
in DCs. Finally, IRF4 directly targets and activates the Il-10 and Il-33 genes in
DCs. Reconstitution with exogenous IL-10 and IL-33 recovers the ability of Irf4
deficient DCs to promote Th2 differentiation. These findings reveal a regulatory
module in DCs by which IRF4 modulates IL-10 and IL-33 cytokine production to
specifically promote Th2 differentiation and inflammation.
PMID- 24356540
TI - Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive
patients.
AB - OBJECTIVE: p63RhoGEF, a guanine nucleotide exchange factor, has been reported 'in
vitro' as key mediator of the angiotensin II-induced RhoA/Rho kinase activation
leading to vasoconstriction and cardiovascular remodeling. We assessed p63RhoGEF
gene and protein expression and RhoA/Rho kinase activity in essential
hypertensive and Bartter's and Gitelman's syndrome patients, a human model
opposite to hypertension; the latter have, in fact, increased plasma angiotensin
II, activation of the renin-angiotensin system, yet normotension/hypotension,
reduced peripheral resistance and lack of cardiovascular remodeling due to an
endogenously blunted angiotensin II type 1 receptor signaling. METHODS:
Mononuclear cell p63RhoGEF gene and protein expression and the phosphorylation
status of the myosin phosphatase target protein-1 (MYPT-1), marker of Rho kinase
activity, were assessed in essential hypertensive patients, Bartter's/Gitelman's
patients and healthy individuals by quantitative real-time PCR and western blot.
RESULTS: p63RhoGEF mRNA and protein level and MYPT-1 phosphorylation status were
higher in hypertensive patients and lower in Bartter's/Gitelman's patients
compared with healthy individuals: p63RhoGEF mRNA level: 0.59 +/- 0.17
DeltaDeltaCt vs. 0.37 +/- 0.17 vs. 0.20 +/- 0.19, analysis of variance (ANOVA): P
<0.016; p63RhoGEF protein level 1.35 +/- 0.14 vs. 1.09 +/- 0.05 vs. 0.90 +/- 0.09
densitometric units, ANOVA: P <0.0001; MYPT-1: 1.39 +/- 0.34 vs. 1.01 +/- 0.12
vs. 0.81 +/- 0.06, ANOVA: P < 0.0001. p63RhoGEF mRNA was significantly correlated
with both SBP and DBP in both hypertensive patients (R = 0.79, P < 0.02 and R =
0.78, P < 0.02) and in Bartter's syndrome/Gitelman's syndrome patients (R = 0.87,
P < 0.001 and R = 0.86, P < 0.001), respectively. CONCLUSION: Increased p63RhoGEF
mRNA and protein level and Rho kinase activity are shown for the first time in
essential hypertensive patients, whereas the opposite was found in
Bartter's/Gitelman's patients, a human model opposite to hypertension. These
results combined with other 'in-vitro' studies strongly support the crucial
importance of p63RhoGEF in Ang II-mediated signaling involved in the regulation
of blood pressure and its long-term complications in humans.
PMID- 24356541
TI - Increased stiffness and cell-matrix interactions of abdominal aorta in two
experimental nonhypertensive models: long-term chemically sympathectomized and
sinoaortic denervated rats.
AB - RATIONALE: Sinoaortic denervated (SAD) and chemically sympathectomized (SNX) rats
are characterized by a decrease in arterial distensibility without hypertension
and would, thus, be relevant for analyzing arterial wall stiffening independently
of blood pressure level. The fibronectin network, which plays a pivotal role in
cell-matrix interactions, is a major determinant of arterial stiffness. We
hypothesized that in SAD and SNX rats, arterial stiffness is increased, due to
alterations of cell-matrix anchoring leading to spatial reorganization of the
extracellular matrix. METHODS: The intrinsic elastic properties of the arterial
wall were evaluated in vivo by the relationship between incremental elastic
modulus determined by echotracking and circumferential wall stress. The changes
of cell-extracellular matrix links in the abdominal aorta were evaluated by
studying fibronectin, vascular integrin receptors, and ultrastructural features
of the aorta by immunochemistry. RESULTS: In both experimental conditions, wall
stiffness increased, associated with different modifications of cell
extracellular matrix adhesion. In SAD rats, increased media cross-sectional area
was coupled with an increase of muscle cell attachments to its extracellular
matrix via fibronectin and its alpha5-beta1 integrin. In SNX rats, reduced media
cross-sectional area was associated with upregulation of alphav-beta3 integrin
and more extensive connections between dense bands and elastic fibers despite the
disruption of the elastic lamellae. CONCLUSION: In aorta of SNX and SAD rats, a
similar arterial stiffness is associated to different structural alterations. An
increase in alphavbeta3 or alpha5beta1 integrins together with the already
reported increase in the proportion of less distensible (collagen) to more
distensible (elastin) components in both models contributes to remodeling and
stiffening of the abdominal aorta.
PMID- 24356542
TI - Report of the 3rd annual International Society of Hypertension New Investigator
Symposium.
PMID- 24356543
TI - Validation method of a middle ear mechanical model to develop a surgical
simulator.
AB - Ossicular surgery requires a high dexterity for the manipulation of the fragile
and small middle ear components. Currently, the only efficient technique for
training residents in otological surgery is through the use of temporal bone
specimens, where any existing surgical simulator does not provide useful
feedback. The objective of this study was to develop a finite-element model of
the human ossicular chain dedicated to surgical simulation and to propose a
method to evaluate its behavior. A model was developed based on human middle ear
micromagnetic resonance imaging. The mechanical parameters were determined
according to published data. To assess its performance, the middle ear transfer
function was analyzed. The robustness of our model and the influence of different
middle ear components were also evaluated at low frequency by static force
pressure simulations. The mechanical behavior of our model in nominal and
pathological conditions was in good agreement with published human temporal bone
measurements. We showed that the cochlea influences the transfer function only at
high frequency and could be omitted from a surgical simulator. In addition,
surgeons were able to manipulate the validated middle ear model with a real-time
haptic feedback. The computational efficiency of our approach allowed real-time
interactions, making it suitable for use in a training simulator.
PMID- 24356544
TI - Activin B promotes initiation and development of hair follicles in mice.
AB - Activin B has been reported to promote the regeneration of hair follicles during
wound healing. However, its role in the development and life cycle of hair
follicles has not been elucidated. In our study, the effect of activin B on mouse
hair follicles of cultured and neonatal mouse skin was investigated. In these
models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle
development was monitored. Hair follicle initiation and development was examined
using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil
Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling
cell apoptosis. Activin B was found to efficiently induce the initiation of hair
follicles in the skin of both cultured and neonatal mice and to promote the
development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated
hair follicles were observed to enter the anagen stage from the telogen stage and
to remain in the anagen stage. These results demonstrate that activin B promotes
the initiation and development of hair follicles in mice.
PMID- 24356545
TI - Effects of the degree of obesity on achieving target blood pressure and metabolic
deterioration in obese individuals: a population-based study.
AB - BACKGROUND/AIMS: This study aimed to evaluate the severity of obesity and its
impact on achieving target blood pressure and metabolic derangement in obese
individuals. METHODS: This cross-sectional and population-based study was
conducted between January and December 2012. A total of 1837 consecutive obese
patients admitted to our outpatient clinic were enrolled. The anthropometric and
blood pressure measurements, bioelectrical impedance fat analysis, blood sample
analysis, impaired glucose status, metabolic syndrome, and insulin resistance of
1265 obese patients were compared between groups of patients separated by
severity of obesity. RESULTS: Only approximately one-third of patients with
previous hypertension achieved normal blood pressure. In addition, the majority
of patients without previous hypertension had higher blood pressure at the end of
the study compared with baseline. The percent of patients with an impaired
fasting blood glucose >=100 mg/dL was 38.5%. The frequency of impaired glucose
tolerance was 39.1% in the patients who underwent OGTT Body mass index (BMI) was
associated with impaired blood glucose, hypertension, insulin resistance, and the
development of metabolic syndrome. The incidences of metabolic syndrome, insulin
resistance, impaired glucose tolerance, and uncontrolled blood pressure were
significantly different between groups of differing obesity severity (p<0.001,
p<0.001, p=0.041, and p<0.001, respectively). CONCLUSION: The severity of obesity
was associated with the failure to achieve target blood pressure and metabolic
syndrome. Based on our data, blood pressure and metabolic parameters in obese
patients should be monitored frequently and treated with caution.
PMID- 24356546
TI - Adult renal size is not a suitable marker for nephron numbers: an individual
patient data meta-analysis.
AB - BACKGROUND: Renal size is often used as a marker for nephron numbers as
estimation of glomerular numbers is not yet possible in vivo. However, the
validity of an association between the two is questionable. As a proper marker
for nephron number in an individual is needed in clinical practice, this study
was designed to assess the association between renal size and nephron numbers.
METHODS: An individual patient data meta-analysis was performed on data retrieved
with a PubMed and Embase search. Only studies were included that described
individual human data on kidney size and nephron numbers determined by
stereology, the gold standard methodology to estimate nephron numbers. As renal
size increases until the end of puberty, and nephron numbers decline after the
age of 60 years, only data from individuals aged 18-60 years without renal
disease were included. RESULTS: Six papers were identified that provided data on
renal weight and nephron numbers from 114 individuals. Backward linear regression
identified kidney weight and race as the only 2 significant factors explaining
nephron numbers (R square 0.085, p=0.007). Controlling for race, there was a
significant correlation between nephron number and kidney weight (r=0.231, r
square=0.053, p=0.01). CONCLUSION: These data indicate that only ~5% of the
variation in nephron numbers is explained by differences in renal size. Renal
size in adulthood should not be used as a marker for nephron numbers in an
individual.
PMID- 24356547
TI - Down-regulation of the Na+-coupled phosphate transporter NaPi-IIa by AMP
activated protein kinase.
AB - BACKGROUND/AIMS: The Na(+)-coupled phosphate transporter NaPi-IIa is the main
carrier accomplishing renal tubular phosphate reabsorption. It is driven by the
electrochemical Na(+) gradient across the apical cell membrane, which is
maintained by Na(+) extrusion across the basolateral cell membrane through the
Na(+)/K(+) ATPase. The operation of NaPi-IIa thus requires energy in order to
avoid cellular Na(+) accumulation and K(+) loss with eventual decrease of cell
membrane potential, Cl(-) entry and cell swelling. Upon energy depletion, early
inhibition of Na(+)-coupled transport processes may delay cell swelling and thus
foster cell survival. Energy depletion is sensed by the AMP-activated protein
kinase (AMPK), a serine/threonine kinase stimulating several cellular mechanisms
increasing energy production and limiting energy utilization. The present study
explored whether AMPK influences the activity of NAPi-IIa. METHODS: cRNA encoding
NAPi-IIa was injected into Xenopus oocytes with or without additional expression
of wild-type AMPK (AMPK(alpha1)-HA+AMPK(beta1)-Flag+AMPK(gamma1)-HA), of inactive
AMPK(alphaK45R) (AMPK(alpha1K45R)+AMPK(beta1)-Flag+AMPK(gamma1)-HA) or of
constitutively active AMPK(gammaR70Q) (AMPK(alpha1)-HA+AMPK(beta1)
Flag+AMPKgamma1(R70Q)). NaPi-IIa activity was estimated from phosphate-induced
current in dual electrode voltage clamp experiments. RESULTS: In NaPi-IIa
expressing, but not in water-injected Xenopus oocytes, the addition of phosphate
(1 mM) to the extracellular bath solution generated a current (Ip), which was
significantly decreased by coexpression of wild-type AMPK and of AMPK(gammaR70Q)
but not of AMPK(alphaK45R). The phosphate-induced current in NaPi-IIa- and AMPK
expressing Xenopus ooocytes was significantly increased by AMPK inhibitor
Compound C (20 uM). Kinetic analysis revealed that AMPK significantly decreased
the maximal transport rate. CONCLUSION: The AMP-activated protein kinase AMPK is
a powerful regulator of NaPi-IIa and thus of renal tubular phosphate transport.
(c) 2013 S. Karger AG, Basel.
PMID- 24356548
TI - Anxiety in children and adolescents with chronic kidney disease--multicenter
national study results.
AB - BACKGROUND/AIMS: Chronic medical illness is a significant risk factor for the
development of psychiatric disorders. The aims of the study were: to investigate
the level of anxiety in children with chronic kidney disease (CKD) and to
identify factors associated with the presence of that emotional problem. METHODS:
CKD children on hemodialysis (HD, n=22), peritoneal dialysis (PD, n=20,) and on
conservative treatment (CT, n=95) were enrolled in the study. We used State-Trait
Anxiety Inventory (STAI) for adolescents and STAI-C for children. Socio
demographic and physical factors were assessed. RESULTS: There was a
significantly higher level of anxiety-state among HD children (8-12 years)
compared with other groups of participants of the same age and Polish population
norms. The level of anxiety among adolescents (13-18 years), both anxiety-state
and anxiety-trait, was significantly higher in the HD group compared with other
groups, which did not differ among themselves. In the HD adolescents, there was a
correlation between the anxiety-state and the duration of the disease as well as
with the number of hospitalizations. PD adolescents in the mainstream education
had higher levels of anxiety-state and anxiety-trait compared with home schooled
patients. CONCLUSIONS: Even though children and adolescents with CKD are at risk
of developing a variety of emotional disorders, the level of anxiety among the
researched group, with the exception of HD patients, was not significantly
different than the level of anxiety among healthy subjects. Adolescents on HD who
present a high level of anxiety should undergo long-term psychological treatment.
PMID- 24356549
TI - Hepatorenal syndrome and novel advances in its management.
AB - Hepatorenal syndrome is a complication of end stage liver disease. It is a unique
form of functional renal failure related to kidney vasoconstriction in the
absence of underlying kidney pathology. Hepatorenal syndrome is classified into 2
types: type-1 HRS shows a rapid and progressive decline in renal function with a
very poor prognosis (median survival of about 2 weeks); type-2 HRS has a more
stable kidney failure, with a median survival of 6 months; its main clinical
manifestation is refractory ascites. The most appropriate therapy for HRS is
liver transplantation but only a minority of HRS patients undergo the procedure
due to the high mortality; survival among liver transplant recipients is lower in
HRS than among their counterparts without HRS. A large body of evidence, based on
observational studies and randomized controlled trials, has been accumulated in
the last decade showing that terlipressin represents a milestone in the
management of HRS. According to our meta-analysis of randomized trials comparing
terlipressin vs. placebo (five trials, n=243 patients), the pooled rate of
patients who reversed HRS by terlipressin was 8.09 (95% CI, 3.52; 18.59)
(P<0.001). Among vasoconstrictors, terlipressin (a V1 vasopressin agonist) is the
most widely used; however, noradrenaline is another good choice. Vasoconstrictor
drugs alone or with albumin reduce mortality compared with no intervention or
albumin (RR of mortality, 0.82; 95% Confidence Intervals, 0.70; 0.96) (P<0.01).
Two series of patients with HRS recurrence after the first treatment have
recently shown that long-term therapy with terlipressin and albumin is beneficial
as a bridge to liver transplant. Nevertheless, recovery of renal function can be
achieved in less than 50% of patients with HRS after terlipressin use and the
recovery of renal function may also be partial in patients who are defined full
responders. Renal replacement therapy should not be considered a first-line
therapy for HRS Clinical trials are under way in order to assess efficacy and
safety of novel therapeutic agents for the treatment of type-1 and type-2 HRS.
PMID- 24356550
TI - Profile of human beta-defensins 1,2 and proinflammatory cytokines (TNF-alpha, IL
6) in patients with chronic kidney disease.
AB - BACKGROUND/AIM: Our aim was to determine whether altered human beta-defensin
(HBD), pro-inflammatory cytokines including interleukin (IL)-6 and tumor necrotic
factor (TNF)-alpha could increase the risk of developing and exacerbation of
chronic kidney disease (CKD), especially for patients with diabetic nephropathy
(DN). METHODS: Serum samples were obtained from 338 CKD patients and 88 sex, age
matched healthy controls. The concentrations of HBD-1 were assayed using an RIA
kit. Serum levels of HBD-2, IL-6 and TNF-alpha were assayed using an ELISA kit.
RESULTS: Serum levels of HBD-1, IL-6 and TNF-alpha were significantly higher in
CKD patients compared to healthy controls (P<0.05). HBD-1 levels were inversely
related to estimated glomerular filtration rate (eGFR), which was the coefficient
factor (beta = -0.357, P = 0.035) explaining the variability in HBD-1 in CKD.
Diabetic nephropathy (DN) patients at stage 3-5 had significantly higher serum
HBD-1 levels than non DN patients (P=0.00). CONCLUSION: Our data support the view
that there is increased inflammation in CKD and DN. The inverse correlation
between eGFR and serum HBD-1 which we observed is suggestive of a relationship
between innate immunity and renal function and should be further investigated.
PMID- 24356551
TI - Associations of smoking with alterations in renal hemodynamics may depend on sex-
investigations in potential kidney donors.
AB - BACKGROUND/AIMS: Cigarette smoking is a risk factor for renal damage, but little
is known about subclinical effects of smoking on renal hemodynamics and
parameters of renal function in humans. We examined the associations of smoking
with systemic and renal hemodynamics and renal function parameters in healthy
individuals. METHODS: Data from 196 potential living kidney donors were analysed
retrospectively. Mean arterial blood pressure (MAP), effective renal plasma flow
(ERPF) and creatinine clearance had been measured. We additionally calculated
parameters of renal hemodynamics. Data were analyzed for the effects of smoking
and sex dependent on age and MAP. RESULTS: Systemic and renal hemodynamic
parameters did not differ between smokers and non-smokers. In non-smokers of both
sexes MAP was negatively correlated with ERPF, and higher MAP was associated with
increased renal vascular resistance and with afferent arteriolar resistance, with
glomerular pressure (PG) remaining constant. However, in male, but not in female
smokers, ERPF and PG increased with MAP. A correlation of age with a steeper
decline in ERPF in male smokers was lost in multiple regression analysis.
CONCLUSIONS: As compared to women, smoking men may exhibit an increased
glomerular hydrostatic pressure, which is a known promoter of kidney damage.
PMID- 24356552
TI - The effects of a single dialysis session on atrial electromechanical conduction
times and functions.
AB - BACKGROUND/AIMS: Abnormalities in atrial electromechanical delay (EMD) times and
mechanical functions are considered as independent predictors of atrial
fibrillation. However, to date, effects of a single hemodialysis (HD) session and
acute volume-preload changes on atrial-EMD functions have not been investigated
by Tissue Doppler Echocardiography (TDE). The aim of the present study was to
evaluate atrial-EMD times and mechanical functions in HD patients. METHODS:
Thirty-five non-diabetic, normotensive HD patients and 35 healthy control
subjects were enrolled in the study. Standard and TDE performed before mid-week
dialysis session for hemodialysis group and on admission for control group.
RESULTS: Interatrial and left-right intraatrial-EMD intervals and left atrial
mechanical volumes were significantly longer in hemodialysis group compared to
controls (all p<0.01) and were reduced after HD session. Furthermore, removed
ultrafiltration volume was associated with reduction in atrial-EMD intervals and
functional volumes. LA-passive emptying volume, ultrafiltration volume, LV-E/E'
ratio, and Vp were independent predictors of interatrial-EMD. CONCLUSIONS: The
present study confirms negative effects in HD patients of structural remodeling
and reveals negative effects of electrical remodeling. Prolonged inter and
intraatrial-EMD intervals should be the underlying pathophysiological factors of
increased rate of atrial fibrillation in the HD population.
PMID- 24356553
TI - Kruppel-like factor 15 modulates renal interstitial fibrosis by ERK/MAPK and
JNK/MAPK pathways regulation.
AB - BACKGROUND/AIMS: Renal interstitial fibrosis is a hallmark of progressive chronic
kidney disease (CKD). Previous studies reported that kruppel-like factor 15
(KLF15) is an important regulator of cardiac fibrosis and could reduce the
expression of extracellular matrix in mesangial cells. However, the role of this
transcription factor in renal interstitial fibrosis has not been reported.
METHODS: In this study, we examined KLF15 expression in the remnant kidney of 5/6
nephrectomized rats 12 or 24 weeks after operation. In vitro we examined the
effect of altered KLF15 expression on the production of extracellular matrix and
the pro-fibrotic factor CTGF in rat renal fibroblasts (NRK-49F), and further
explored the related mechanisms. RESULTS: The level of KLF15 was drastically
decreased in the renal interstitium of 5/6 nephrectomized rats with progressive
interstitial fibrosis, especially at 24 weeks. Our in vitro evidence showed that
overexpression of KLF15 repressed basal and transforming growth factor-beta1 (TGF
beta1)-induced extracellular matrix and CTGF in NRK-49F cells. In addition, TGF
beta1-mediated activation of extracellular-regulated kinase (ERK) / mitogen
activated protein kinase (MAPK) and Jun N-terminal kinase (JNK) /MAPK
downregulated KLF15 expression and increased the level of extracellular matrix
and CTGF, and all these effects were completely abolished by ERK1/2 inhibitor and
JNK inhibitor in NRK-49F cells. CONCLUSIONS: Our findings implicate that KLF15
plays an important role and may prove to be an antifibrotic factor in renal
interstitial fibrosis through regulation of ERK/MAPK and JNK/MAPK signaling
pathways.
PMID- 24356554
TI - A candidate gene approach to ANCA-associated vasculitis reveals links to the C3
and CTLA-4 genes but not to the IL1-Ra and Fcgamma-RIIa genes.
AB - BACKGROUND/AIMS: The aim of the study is to search for associations between
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and
polymorphisms in the genes of four key molecules possibly involved in different
pathogenic pathways; complement C3, CTLA-4, Fcgamma-RIIa and IL1-Ra. PATIENTS AND
METHODS: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or
granulomatosis with polyangiitis (Wegener's granulomatosis) and myeloperoxidase
(MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200
blood donors. Polymorphisms in the genes were analysed with PCR amplification of
DNA. RESULTS: The diagnosis of AAV was confirmed in the 105 cases. The gene
frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in
the control group. The number of patients homozygous for the shortest 86 bp
allele of CTLA-4 was significantly decreased in the whole group of patients
(p=0.049). No differences were evident in the Fcgamma-RIIa and IL1-Ra
polymorphisms when compared to controls, neither in the whole group of patients,
nor in any of the sub-groups. CONCLUSION: The aberrant gene frequency of the C3F
allele among PR3-ANCA positive patients and the findings with the CTLA-4
polymorphism indicates that complement may be involved in pathogenesis and that T
cell activation also is of importance in these diseases.
PMID- 24356555
TI - Long-term survival of patients with IgA nephropathy after dialysis therapy.
AB - BACKGROUND/AIMS: How dialysis affects the survival of patients with biopsy-proven
IgA nephropathy (IgAN) is not fully understood. The present long-term cohort
study quantifies the survival rates and incidence of cardio-cerebrovascular
diseases (CCVDs) among such patients in Japan. METHODS: Fifty-two of 433 patients
with IgAN who had reached end-stage kidney disease underwent renal replacement
therapy (RRT) between 1981 and 2010. The overall survival rate and incidence of
CCVDs in these patients were evaluated during follow-up for 11.3 +/- 6.4 years.
RESULTS: The mean age at starting RRT was 42.8 +/- 13.3 years. Only seven
patients died during follow-up (mortality rate, 1.2/100 person-years) and Kaplan
Meier analysis revealed favorable survival rates of 93.3% and 65.1% at 10 and 20
years, respectively, compared with that of patients with glomerulonephritis in
the registry of the Japanese Society for Dialysis Therapy who required RRT.
Malignancy and CCVDs were causes of death at 13.6 +/- 4.8 and 3.9 +/- 1.3 years,
respectively, after starting RRT. Fatal and non-fatal CCVDs developed in 15
(incidence, 2.7/100 person-years) patients and acute coronary syndrome and
cerebral hemorrhage developed relatively soon after starting RRT. Cox
proportional hazards models revealed that age at the time of starting RRT was a
significant factor affecting the onset of CCVDs. Meanwhile, a history of having
had corticosteroid as an initial treatment did not affect the onset of events.
CONCLUSION: Although the survival of patients with IgAN is favorable after
dialysis, the onset of CCVDs during the early phase of dialysis should be
carefully monitored.
PMID- 24356556
TI - Brain natriuretic peptides in atherosclerotic renal artery stenosis and effects
of renal angioplasty.
AB - BACKGROUND: We hypothesized that plasma levels of brain natriuretic peptide (BNP)
and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin
concentrations reduced, in patients with atherosclerotic renal artery stenosis
(ARAS) and that BNPs might be used to identify patients who would benefit from
percutaneous transluminal renal angioplasty (PTRA). METHODS: Data were collected
before renal angiography in 91 patients with hypertension and suspected ARAS
(significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In
ARAS patients analyses were repeated four weeks after PTRA. RESULTS: Ambulatory
systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs.
both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were
significantly elevated, and adiponectin concentrations reduced, in the ARAS group
vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs.
baseline (149+/-16 to 139+/-15 mm p<0.01). Brain natriuretic peptides were not
significantly affected by PTRA. CONCLUSIONS: Patients with ARAS showed elevated
of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared
to healthy controls but not vs. hypertensive individuals without RAS. Our data do
no support the use of BNP analyses in the identification of ARAS patients who
will have a beneficial blood pressure response to PTRA.
PMID- 24356557
TI - New insights on the role of vitamin D in the progression of renal damage.
AB - Several studies indicate a relationship between hypovitaminosis D, survival,
vascular calcification and inflammation. In addition to its central role in the
regulation of bone mineral metabolism, vitamin D also contributes to other
systems, including the immune, cardiovascular and endocrine systems. Vitamin D
analogs reduces proteinuria, in particular through suppression of the renin
angiotensin-aldosterone system (RAAS) and exerts anti-inflammatory and
immunomodulatory effects. In particular vitamin D deficiency contribute to an
inappropriately activated RAAS, as a mechanism for progression of chronic kidney
disease (CKD) and/or cardiovascular disease. Human and sperimental models of CKD
showed that vitamin D may interact with B and T lymphocytes and influence the
phenotype and function of the antigen presenting cells and dendritic cells,
promoting properties that favor the induction of tolerogenic T regulators rather
than T effectory. Interstitial fibrosis may be prevented through vitamin D
supplementation. Renal myofibroblast, an activated fibroblast with expression of
a molecular hallmark alpha-smooth muscle actin (alpha-SMA), is generally
considered the principal matrix-producing effector cells that are responsible for
the excess production of extracellular matrix (ECM) components in the fibrotic
tissues. It turns out that calcitriol effectively blocks myofibroblast activation
from interstitial fibroblasts, as evidenced by suppression of TGF-beta1-mediated
alpha-SMA expression.
PMID- 24356559
TI - Butterfly-like enantiomerically homochiral {Co(II)6Co(III)4} clusters exhibiting
both slow magnetic relaxation and ferroelectric property.
AB - A pair of enantiomerically homochiral {Co(II)6Co(III)4} clusters featuring a
butterfly-like structure, [Co(II)6Co(III)4(MU3-OH)(MU3-X)(S
pa)4(pdm)6(pdmH)2](ClO4)4.3.5H2O (S-1) and [Co(II)6Co(III)4(MU3-OH)(MU3-X)(R
pa)4(pdm)6(pdmH)2](ClO4)4.3.5H2O (R-1) (X = OH or OMe, S- or R-paH = S- or R
phenylalaninol and pdmH2 = pyridine-2,6-diyldimethanol), have been synthesized
and structurally characterized. They are the second largest homochiral Co
clusters constructed by chiral ligands. They are also the first example of high
nuclearity homochiral Co clusters having both slow magnetic relaxation behaviour
and ferroelectric property.
PMID- 24356558
TI - Idiopathic pulmonary fibrosis: from epithelial injury to biomarkers--insights
from the bench side.
AB - Idiopathic pulmonary fibrosis (IPF) is the most frequent fibrotic diffuse
parenchymal lung disease. Its prognosis is devastating: >50% of the patients die
within 3 years after diagnosis. Options for the treatment of IPF are limited and
lung transplantation is the only 'curative' therapy. Currently, in the absence of
validated indicators of disease progression/activity and diagnostic tools, the
clinical management of IPF remains a major challenge. A better understanding of
the pathogenesis of IPF is critical for the identification of new therapeutic
targets as well as molecules that may serve as surrogate markers for clinically
significant endpoints. The current paradigm on the mechanisms leading from a
normal to a fibrotic lung postulates that chronic epithelial lesion leads to
aberrant wound healing activation, which is characterized by deregulated
fibroblast proliferation and activation together with an uncontrolled
extracellular matrix synthesis. In this review, we shed light on the role of
epithelial cell damage in the pathogenesis of fibrosis. Finally, we examine the
markers of epithelial damage and their potential use as biomarkers and the future
of this continuously expanding field.
PMID- 24356561
TI - Fabrication and microwave absorption properties of carbon-coated cementite
nanocapsules.
AB - By utilizing a simple and low-cost arc-discharge method in either liquid nitrogen
or ethanol at ambient temperature and pressure, carbon-coated cementite (Fe3C)
nanocapsules, with size ranges of 10-60 nm and 10-20 nm, respectively, have been
synthesized on a large scale. The Fe3C/C nanocapsules synthesized in different
media possess similar permeability but different permittivity, which results from
the different defect amounts within the carbon shell. It has been found that the
as-prepared products exhibit different electromagnetic wave absorption abilities:
for the ones prepared in liquid nitrogen, the optimal reflection loss is above
10 dB in the range of 1-18 GHz with the thickness ranging from 1 to 10 mm;
meanwhile, for those fabricated in ethanol, the reflection loss could be below
20 dB within the thickness range of 1.5-2.4 mm in the frequency range of 10-15
GHz, and reach -38 dB at a thickness of 1.9 mm with a matching frequency of 12.9
GHz. This indicates that the nanocapsules prepared in ethanol exhibit good
electromagnetic wave absorption properties. These results provide a new way to
fabricate carbon-coated Fe3C nanocapsules with the ability of electromagnetic
wave absorption.
PMID- 24356560
TI - Discovery and expression analysis of alternative splicing events conserved among
plant SR proteins.
AB - The high frequency of alternative splicing among the serine/arginine-rich (SR)
family of proteins in plants has been linked to important roles in gene
regulation during development and in response to environmental stress. In this
article, we have searched and manually annotated all the SR proteins in the
genomes of maize and sorghum. The experimental validation of gene structure by
reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed, with
few exceptions, that SR genes produced multiple isoforms of transcripts by
alternative splicing. Despite sharing high structural similarity and conserved
positions of the introns, the profile of alternative splicing diverged
significantly between maize and sorghum for the vast majority of SR genes. These
include many transcript isoforms discovered by RT-PCR and not represented in
extant expressed sequence tag (EST) collection. However, we report the occurrence
of various maize and sorghum SR mRNA isoforms that display evolutionary
conservation of splicing events with their homologous SR genes in Arabidopsis and
moss. Our data also indicate an important role of both 5' and 3' untranslated
regions in the regulation of SR gene expression. These observations have
potentially important implications for the processes of evolution and adaptation
of plants to land.
PMID- 24356562
TI - Evaluation of cardiotoxicity via speckle-tracking echocardiography in patients
treated with anthracyclines.
AB - BACKGROUND: The aim of this study was to examine the cardiac effects of
anthracycline therapy based on speckle-tracking echocardiography (STE) and to
identify patients at risk for cardiotoxicity. PATIENTS AND METHODS: The study
included 35 breast cancer (BC) and 15 lymphoma patients who were treated with
anthracycline-based chemotherapy. Conventional echocardiography and STE were
performed 1 month prior to and 1 month after chemotherapy. Longitudinal strain
analysis was performed via STE using automated functional imaging. RESULTS: The
ejection fraction (EF) and the fractional shortening values were significantly
lower in the lymphoma group. There was a positive correlation between
anthracycline dose and subclinical heart failure (p = 0.024). There was an
increase in the myocardial performance index in both groups. After therapy, STE
showed regional decreases in the longitudinal strain values in the BC group, but
the global strain values did not differ. In the lymphoma group, the apical long
axis, the 4-chamber, and the global longitudinal strain values were significantly
lower after therapy (p = 0.002, 0.041, and 0.004, respectively). The long-axis
and global longitudinal strain values were significantly lower in the lymphoma
patients with normal EF values (p = 0.01 and 0.05, respectively). CONCLUSION:
Cardiotoxicity during the early phase of anthracycline treatment can be detected
via STE prior to the observation of systolic function deterioration.
PMID- 24356563
TI - RAS, BRAF, and TP53 gene mutations in Taiwanese colorectal cancer patients.
AB - BACKGROUND: Colorectal cancer (CRC) plays an important role in cancer mortality
and morbidity. This study examined colorectal tissues for RAS, BRAF, and TP53
gene mutations to assess their value as indicators of outcomes of CRC therapy.
MATERIAL AND METHODS: DNA was extracted from tissues taken from 165 patients with
CRC. RAS gene mutations (exons 2 and 3) were detected by primer extension
analysis. BRAF gene mutations (V600E) were detected by high resolution melting
(HRM) analysis. TP53 gene mutations (exons 5-8) were detected by direct
sequencing. RESULTS: RAS, BRAF, and TP53 mutations occurred in 36.97% (61/165),
4.24% (7/165), and 37.58% (62/165), respectively. The KRAS mutation is a
predictor for poor 5-year survival (p = 0.05), and the co-presence of KRAS and
TP53 mutations correlates with lymph node involvement (p = 0.029), tumor stage (p
= 0.029), and poor survival (p = 0.021). Multivariate analysis adjusted for tumor
size, histologic grade, lymph node metastasis, sex, and age also indicated that
KRAS mutations correlate significantly with overall survival (p = 0.036).
CONCLUSION: The KRAS mutation is not present in about one-third of CRC patients,
and therefore other gene mutations need to be investigated to better understand
the molecular mechanisms of CRC and its treatment.
PMID- 24356564
TI - Treatment of primary breast cancer at the surgical unit of the Charite 1984-1998.
AB - BACKGROUND: We have analyzed the patient population of one clinic (Charite) over
a period of 15 years. Besides the changes in the technical facilities and
therapeutical guidelines during these years, this period also reflects the
changes in the health system attributable to the reunification of East and West
Germany. Until now only few analyses for breast cancer patients from the German
speaking area have been reported. PATIENTS AND METHODS: All 2,062 patients
undergoing surgical treatment for breast cancer between 1984 and 1998 were
documented and followed up until 2007. The analysis included 1,560 patients with
a primary breast cancer who fulfilled certain inclusion criteria. The treatment
strategies applied to this population are presented in 3 time periods (1984-1990,
1991-1993, and 1994-1998). The effects of prognostic factors on overall survival
were investigated using univariate analyses. RESULTS: The percentage of pT1
tumors changed from 50.7% in the first period to 63.1% in the third period. The
percentage of node-negative patients hardly changed with time (on average 61.6%).
However, the percentage of patients with less than 10 assessed nodes decreased
from 48.4% to 6.7% and 2.5% for the 3 periods, respectively. Therapeutic
strategies changed drastically. Survival rate increased substantially, most
likely due to improved therapeutic strategies, but also for other reasons not
considered in the analysis.
PMID- 24356565
TI - Patient-related delay in presentation for cutaneous squamous cell carcinoma. A
cross-sectional clinical study.
AB - BACKGROUND: Delayed diagnosis of squamous cell carcinoma (SCC) increases
recurrence, metastatic potential, and management costs. This study aims to
identify risk factors of patient-related delayed presentation in cutaneous SCC.
PATIENTS AND METHODS: A total of 513 patients, who first sought care for
cutaneous lesions that were subsequently removed and histologically confirmed as
SCCs, were included. Attitude to symptoms, psychosocial profile, and reasons for
delayed presentation were obtained via a structured questionnaire-based
interview. First presentation > 3 months from the onset of symptoms was
considered as delayed. RESULTS: Mean presentation time was 3.90 +/- 2.05 months,
while 186 patients delayed presentation. Multivariate logistic regression
analysis revealed that serious co-morbidity (p = 0.003), low education level (p <
0.001), non-recognition of the seriousness of symptoms (p < 0.001), a 'wait and
see' attitude (p < 0.001), and fatalism (p = 0.005) were independent determinants
of significantly higher risk for delayed presentation. In contrast, female sex (p
= 0.006), new lesion (p = 0.012), accessible topography (p = 0.019), size
increase (p = 0.002), color change (p = 0.017), non-healing wound (p = 0.048),
and presence of social support/advice (p < 0.001) were independent determinants
significantly associated with early presentation. CONCLUSION: Recognition of
symptom seriousness and elimination of factors hindering self-referral may
increase awareness and promote early patient presentation and diagnosis of
cutaneous SCC.
PMID- 24356566
TI - A meta-analysis of internal mammary lymph node metastasis in breast cancer
patients.
AB - BACKGROUND: Knowing the status of the internal mammary lymph (IML) nodes is
important for accurate staging and appropriate selection of subsequent treatment
in breast cancer. We conducted a meta-analysis to clarify the rate of IML node
metastasis in breast cancer patients and discussed the importance of this
finding. METHODS: We retrieved articles from the literature that reported
positive rates of IML node metastasis in breast cancer patients. The quality of
the selected articles was assessed using the 'Methodological Index for Non
Randomized Studies'. The heterogeneity was tested, and publication bias was
assessed using a funnel plot. Finally, the positive rate of IML node metastasis
in breast cancer patients was calculated using the random-effects model. RESULTS:
15 articles met the inclusion criteria and a total of 4,248 patients were
included in the analysis. Heterogeneity across the studies was statistically
significant (p = 0.014); thus, the random-effects model was used and the
calculated positive rate of IML node metastasis was 23% (95% confidence interval
(CI), 0.21-0.25). CONCLUSIONS: Approximately 23% of the breast cancer patients
had IML node metastases, for which the prognosis is generally poor. Accurate
staging and integrated treatment are necessary to improve the survival of these
patients.
PMID- 24356567
TI - miR-145 inhibits proliferation and invasion of esophageal squamous cell carcinoma
in part by targeting c-Myc.
AB - BACKGROUND: Accumulating evidence has shown that microRNAs (miRNAs) are
aberrantly expressed in human esophageal cancer and crucial to tumorigenesis.
Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma
(ESCC) development in vitro and in vivo. MATERIAL AND METHODS: miR-145 expression
was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time
polymerase chain reaction. Crystal violet and transwell assays were conducted to
explore the effects of miR-145 on the proliferation and invasion of human ESCC
cell lines, respectively. The impact of overexpression of miR-145 on putative
target c-Myc was subsequently confirmed via Western blot. RESULTS: miR-145
expression was frequently downregulated in ESCC specimens and cell lines compared
with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p
< 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft
tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the
protein level of c-Myc which has previously been identified as a direct target of
miR-145. CONCLUSION: Our results demonstrate that overexpression of miR-145
inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR
145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved
in the initiation and development of human ESCC.
PMID- 24356568
TI - Metastatic germ cell tumour following renal transplantation.
AB - BACKGROUND: Treatment of germ cell tumours with cisplatin-based chemotherapy
results in cure for the majority of patients. There is, however, a small but
significant mortality rate, reported to be higher in patients with multiple co
morbidities. CASE REPORT: We report our management of a renal transplant patient
with spina bifida, who was diagnosed with stage IIIC, poor-risk, non-seminomatous
germ cell carcinoma. A marker-negative partial response, which has been
maintained more than 2 years following completion of treatment, was seen
following chemotherapy with cisplatin and etoposide. Performance status has been
preserved at pre-treatment levels. CONCLUSION: Administration of cisplatin-based
chemotherapy is feasible for treatment of renal transplant patients with advanced
non-seminomatous germ cell tumours. Treatment strategies require careful planning
and monitoring. Dose modifications may be required. This case highlights a
favourable outcome in spite of multiple obstacles to ideal management.
PMID- 24356569
TI - Successful treatment with nab-paclitaxel and gemcitabine after FOLFIRINOX failure
in a patient with metastasized pancreatic adenocarcinoma.
AB - BACKGROUND: Advanced pancreatic adenocarcinoma still remains associated with a
desperate prognosis. Nevertheless, treatment options for patients with
metastasized disease have improved considerably over the last few years.
Recently, cytotoxic combination therapies such as the FOLFIRINOX regimen and
combined nab-paclitaxel/gemcitabine have shown improved overall survival compared
to gemcitabine alone. There is still no standard of care in second-line therapy
for patients with disease progression. CASE REPORT: We report the case of a 47
year-old patient who dramatically responded to second-line treatment with nab
paclitaxel and gemcitabine after primary progression to the FOLFIRINOX protocol.
CONCLUSION: Second-line treatment after FOLFIRINOX is feasible for patients with
good performance status. Our case report supports preclinical findings that
suggest that pancreatic cancer is a heterogeneous disease. Further studies that
characterize possible subgroups and identify predictive molecular markers to
guide therapy are warranted.
PMID- 24356570
TI - Anti-HPV-E7 seropositivity and risk of esophageal squamous cell carcinoma in a
high-risk population in China.
AB - Results of previous serologic studies on the association of human papillomavirus
(HPV) with esophageal squamous cell carcinoma (ESCC) have been inconsistent. From
2007 to 2010, the authors collected blood samples and relevant demographic data
from 1435 patients with ESCC and 2071 age- and sex-matched normal controls from
Anyang, China. HPV-16, 18 and 57 E7 antibodies were evaluated with the
glutathione-S-transferase capture ELISA. The proportions of subjects who were
positive for antibodies against these three HPV antigens in the case group were
all significantly higher than those in the control group. In multivariate
analysis, the presence of HPV-16 E7 antibody was associated with an increased
risk of ESCC [odds ratio (OR) = 3.6, 95% confidence interval (CI): 2.5-5.0],
whereas the presence of HPV-18 (OR = 1.1, 95% CI: 0.7-1.7) and HPV-57 (OR = 1.3,
95% CI: 0.9-1.9) antibodies were not significant after adjustment for HPV-16. In
multiple cutoff value analysis, the lowest OR for HPV-16 was obtained with the
standard cut point mean + 3 SD. This study provides serological evidence in
support of HPV-16 infection playing a role in the occurrence of ESCC in a high
incidence area of China.
PMID- 24356571
TI - A Comment on Qi et al. An Estimation of Radiobiological Parameters for Head-and
Neck Cancer Cells and the Clinical Implications-Authors' Reply.
AB - We appreciate the thoughtful comments from Dr. Jack Fowler on our recent
manuscript of an estimation of radiobiological parameters for head and neck
cancer (HNC) and the clinical implications [1]. [...].
PMID- 24356573
TI - Response to "Salt: the dying echoes of the food industry".
PMID- 24356574
TI - Salt: the dying echoes of the food industry.
PMID- 24356572
TI - Regulatory RNAs: charming gene management styles for synthetic biology
applications.
AB - RNAs have many important functional properties, including that they are
independently controllable and highly tunable. As a result of these advantageous
properties, their use in a myriad of sophisticated devices has been widely
explored. Yet, the exploitation of RNAs for synthetic applications is highly
dependent on the ability to characterize the many new molecules that continue to
be discovered by large-scale sequencing and high-throughput screening techniques.
In this review, we present an exhaustive survey of the most recent synthetic
bacterial riboswitches and small RNAs while emphasizing their virtues in gene
expression management. We also explore the use of these RNA components as
building blocks in the RNA synthetic biology toolbox and discuss examples of
synthetic RNA components used to rewire bacterial regulatory circuitry. We
anticipate that this field will expand its catalog of smart devices by mimicking
and manipulating natural RNA mechanisms and functions.
PMID- 24356575
TI - The effect of silymarin on mesenteric ischemia-reperfusion injury.
AB - OBJECTIVE: To examine the effect of silymarin (SM), a mixture of flavonoids and
polyphenols extracted from Silybum marianum, on mesenteric ischemia-reperfusion
(I-R) injury in a rat model. MATERIALS AND METHODS: Fifty rats were randomly
divided into 5 groups (n = 10). Group 1 was sham operated, while groups 2-5 were
subjected to mesenteric I-R lasting 1 h. Group 2 received isotonic sodium
chloride, group 3 received SM (100 mg/kg/day) for 7 days before I-R, group 4
received SM for 7 days after I-R, and group 5 received SM for 7 days both before
and after I-R. The rats were sacrificed by exsanguination in groups 1-3 at the
24th hour and groups 4 and 5 were sacrificed on the 7th day of reperfusion. Blood
and intestinal specimens were taken for biochemical and pathological evaluations.
RESULTS: Serum superoxide dismutase (SOD) and heat shock protein 70 levels were
significantly higher in group 2 (5.24 +/- 1.76 U/l and 261.4 +/- 16.8 ng/ml)
compared to the sham group (2.08 +/- 1.76 U/l and 189.9 +/- 28.7 ng/ml) (p <
0.001 and p < 0.0001, respectively). However, SOD activity and the extent and
severity of the histopathological lesions were significantly less in groups 3
[3.11 +/- 1.18 U/l, 1.0 (range 0.0-2.0)], 4 [2.15 +/- 0.87 U/l, 1.0 (range 1.0
3.0)], and 5 [1.80 +/- 0.61 U/l, 0.5 (range 0.0-2.0)], treated with SM, than in
group 2 [5.24 +/- 1.76 U/l, 2.0 (range 2.0-3.0)] (p = 0.002, p < 0.001, and p =
0.0001; p < 0.001, p = 0.007, and p = 0.0001, respectively). Also, TNF-alpha
levels were lower in the SM-supplemented groups compared to group 2. Serum
thiobarbituric acid-reactive substance concentrations were low in the pre
/posttreatment groups treated with SM compared to group 2. No statistical
difference was observed for protein carbonyls between the groups. CONCLUSION: Our
findings suggest that SM therapy may attenuate the oxidative and intestinal
damage induced by I-R injuries.
PMID- 24356576
TI - Hedgehog and Notch signaling in enteric nervous system development.
AB - The enteric nervous system (ENS) in mammals is derived from a small pool of
progenitor cells, namely enteric neural crest cells (NCCs). These precursor cells
proliferate extensively to expand, migrate over a long distance to fully colonize
the developing gut and differentiate into millions of neurons and glia to form a
functional ENS for regulating the complex behaviors of the gut. This
developmental process relies on a precise regulation of the neuronal and glial
differentiation and requires an appropriate balance between the migration,
proliferation and differentiation of enteric NCCs and their progeny. Hedgehog
(Hh) and Notch signalings are essential for almost every aspect of ENS
development, and they confer both the long- and short-range signals to coordinate
these seemingly diverse cellular processes. In this review, we summarize the
roles of Hh and Notch signaling, particularly in the context of gut organogenesis
and ENS development and emphasize how combinatory Hh and Notch signaling renders
functional diversity as well as specificity.
PMID- 24356577
TI - Overlapped optics induced perfect coherent effects.
AB - For traditional coherent effects, two separated identical point sources can be
interfered with each other only when the optical path difference is integer
number of wavelengths, leading to alternate dark and bright fringes for different
optical path difference. For hundreds of years, such a perfect coherent condition
seems insurmountable. However, in this paper, based on transformation optics, two
separated in-phase identical point sources can induce perfect interference with
each other without satisfying the traditional coherent condition. This shifting
illusion media is realized by inductor-capacitor transmission line network.
Theoretical analysis, numerical simulations and experimental results are
performed to confirm such a kind of perfect coherent effect and it is found that
the total radiation power of multiple elements system can be greatly enhanced.
Our investigation may be applicable to National Ignition Facility (NIF), Inertial
Confined Fusion (ICF) of China, LED lighting technology, terahertz communication,
and so on.
PMID- 24356578
TI - Alteration of mevalonate pathway related enzyme expressions in pressure overload
induced cardiac hypertrophy and associated heart failure with preserved ejection
fraction.
AB - BACKGROUND: Abnormalities of the mevalonate pathway, an important cellular
metabolic pathway, are common in many diseases including cardiovascular disease.
The mevalonate pathway related enzyme expressions in pressure overload-induced
cardiac hypertrophy and associated diastolic dysfunction remains largely unknown.
This study aims to investigate whether the expression of mevalonate pathway
related enzyme is altered during the progression of cardiac hypertrophy and
associated diastolic dysfunction induced by pressure overload. METHODS: Male
Sprague-Dawley (SD) rats were randomly divided into two groups: the suprarenal
abdominal aortic coarctation (AAC) group and the sham group. RESULTS:
Histological and echocardiographic assessments showed that there was a
significant cardiovascular remodeling in the AAC group compared with the sham
group after 3 weeks post-operatively, and the left ventricular (LV) diastolic
function was reduced at 8 and 14 weeks post-operatively in the AAC group, without
any change in systolic function during the study. The tissue of the heart and the
abdominal aorta proximal to the coarctation showed over-expression of several
enzymes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR),
farnesyl diphosphate synthase (FDPS), farnesyltransferase-alpha (FNTA),
farnesyltransferase-beta (FNTB), geranylgeranyltransferase type I (GGTase-I) and
the activation of their downstream proteins was enhanced. CONCLUSIONS: AAC
induced compensatory LV hypertrophy to decompensatory diastolic dysfunction,
accompanied by altered expression of several key enzymes in the mevalonate
pathway.
PMID- 24356579
TI - The relationship of bedside nurses' emotional intelligence with quality of care.
AB - Emotional intelligence, a predictor of productivity and success, may impact
behaviors responsible for quality of care. This study examined if emotional
intelligence of units' bedside nurses is related to the quality of care delivered
to the patients. In this study, emotional intelligence was found to be correlated
to the number of Clostridium difficile infections, MRSA infections, patient falls
with injury, and pressure ulcer screenings (P < .001) in the inpatient acute care
setting.
PMID- 24356580
TI - Hypovitaminosis D and executive dysfunction in older adults with memory
complaint: a memory clinic-based study.
AB - BACKGROUND: Hypovitaminosis D is associated with executive dysfunction as a
whole. The purpose of this cross-sectional study was to determine whether lower
vitamin D levels were associated with mental flexibility, information updating,
or cognitive and motor inhibition among older adults. METHODS: One hundred
Caucasian older community dwellers with memory complaint (mean, 71.02 +/- 0.74
years; 52.0% female) were divided into 3 groups according to serum 25
hydroxyvitamin D (25-OHD) concentration (deficiency <25 nmol/l, insufficiency 25
50 nmol/l, sufficiency >50 nmol/l). Executive functions were assessed with error
rates by executing the Trail Making Test-B (TMT-B) for mental flexibility, the N
Back Test for information updating, the Stroop Interference Test for cognitive
inhibition, and the Go/No-Go score for motor inhibition. Age, gender, BMI,
education level, number of morbidities, depressive symptoms, Mini-Mental State
Examination score, calcemia, estimated glomerular filtration rate and season
tested were considered as potential confounders. RESULTS: Compared to
participants with vitamin D insufficiency and sufficiency, those with vitamin D
deficiency had a poorer TMT-B performance (p = 0.019 and p = 0.017, respectively)
but similar N-Back (p = 0.175), Stroop (p = 0.135) and Go/No-Go (p = 0.224)
scores. Cognitive performance did not differ between participants with
insufficient and sufficient vitamin D levels. Vitamin D deficiency was associated
with poorer performance on TMT-B (adjusted beta = 1.48, p = 0.011), but not on N
Back (p = 0.665), Stroop (p = 0.817) or Go/No-Go (p = 0.971). CONCLUSION: Vitamin
D deficiency was associated with poorer mental flexibility among older community
dwellers with memory complaint.
PMID- 24356581
TI - The role of neurokinin B signalling in reproductive neuroendocrinology.
AB - The KNDy neuropeptides, kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn),
have been implicated in regulating pulsatile luteinising hormone (LH) secretion.
Studies of the interactions between KNDy signalling systems, however, are
currently few. Although the stimulatory effect of kisspeptin and the inhibitory
effect of Dyn on the gonadotropin-releasing hormone pulse generator are widely
accepted, the effects of NKB in rodents are variable and sometimes controversial.
Literature describing increased LH secretion in response to NKB receptor agonism
predominates and is in line with human physiology, as well as the pathophysiology
of pubertal failure associated with disruption of NKB signalling. However, the
robust suppression of the LH pulse, induced by the same treatment under
hypoestrogenic conditions, may hold clues as to the mechanisms of reproductive
inhibition under pathological conditions. This review discusses the recent
evidence for this paradox and outlines a revised working model incorporating the
mechanisms by which KNDy neuropeptides modulate the reproductive axis.
PMID- 24356582
TI - Poly(ADP-ribose) binding to Chk1 at stalled replication forks is required for S
phase checkpoint activation.
AB - Damaged replication forks activate poly(ADP-ribose) polymerase 1 (PARP1), which
catalyses poly(ADP-ribose) (PAR) formation; however, how PARP1 or poly(ADP
ribosyl)ation is involved in the S-phase checkpoint is unknown. Here we show that
PAR, supplied by PARP1, interacts with Chk1 via a novel PAR-binding regulatory
(PbR) motif in Chk1, independent of ATR and its activity. iPOND studies reveal
that Chk1 associates readily with the unperturbed replication fork and that PAR
is required for efficient retention of Chk1 and phosphorylated Chk1 at the fork.
A PbR mutation, which disrupts PAR binding, but not the interaction with its
partners Claspin or BRCA1, impairs Chk1 and the S-phase checkpoint activation,
and mirrors Chk1 knockdown-induced hypersensitivity to fork poisoning. We find
that long chains, but not short chains, of PAR stimulate Chk1 kinase activity.
Collectively, we disclose a previously unrecognized mechanism of the S-phase
checkpoint by PAR metabolism that modulates Chk1 activity at the replication
fork.
PMID- 24356583
TI - APEX (Aqueous Photochemistry of Environmentally occurring Xenobiotics): a free
software tool to predict the kinetics of photochemical processes in surface
waters.
AB - The APEX software predicts the photochemical transformation kinetics of
xenobiotics in surface waters as a function of: photoreactivity parameters
(direct photolysis quantum yield and second-order reaction rate constants with
transient species, namely OH, CO3(-), (1)O2 and the triplet states of
chromophoric dissolved organic matter, (3)CDOM*), water chemistry (nitrate,
nitrite, bicarbonate, carbonate, bromide and dissolved organic carbon, DOC), and
water depth (more specifically, the optical path length of sunlight in water). It
applies to well-mixed surface water layers, including the epilimnion of
stratified lakes, and the output data are average values over the considered
water column. Based on intermediate formation yields from the parent compound via
the different photochemical pathways, the software can also predict intermediate
formation kinetics and overall yield. APEX is based on a photochemical model that
has been validated against available field data of pollutant phototransformation,
with good agreement between model predictions and field results. The APEX
software makes allowance for different levels of knowledge of a photochemical
system. For instance, the absorption spectrum of surface water can be used if
known, or otherwise it can be modelled from the values of DOC. Also the direct
photolysis quantum yield can be entered as a detailed wavelength trend, as a
single value (constant or average), or it can be defined as a variable if
unknown. APEX is based on the free software Octave. Additional applications are
provided within APEX to assess the sigma-level uncertainty of the results and the
seasonal trend of photochemical processes.
PMID- 24356585
TI - Transplantation of N -acetyl aspartyl-glutamate synthetase-activated neural stem
cells after experimental traumatic brain injury significantly improves
neurological recovery.
AB - BACKGROUND/AIMS: Neural stem cells (NSCs) hold considerable potential as a
therapeutic tool for repair of the damaged nervous system. In the current study,
we examined whether transplanted N-acetyl aspartyl-glutamate synthetase (NAAGS)
activated NSCs (NAAGS/NSCs) further improve neurological recovery following
traumatic brain injury (TBI) in Sprague-Dawley rats. METHODS: Animals received
TBI and stereotactic injection of NSCs, NAAGS/NSCs or phosphate buffered saline
without cells (control) into the injured cortex. NAAGS protein expression was
detected through western blot analysis. Dialysate NAAG levels were analyzed with
radioimmunoassay. Cell apoptosis was detected via TUNEL staining. The expression
levels of specific pro-inflammatory cytokines were detected with enzyme-linked
immunosorbent assay. RESULTS: Groups with transplanted NSCs and NAAGS/NSCs
displayed significant recovery of the motor behavior, compared to the control
group. At 14 and 21 days post-transplantation, the motor behavior in NAAGS/NSC
group was significantly improved than that in NSC group (p<0.05). Additionally,
transplanted NAAGS/NSCs inhibited cell apoptosis and the expression levels of
specific pro-inflammatory cytokines, including interleukin-1beta, interleukin-6
and tumor necrosis factor-alpha. CONCLUSION: Our results collectively demonstrate
that NAAGS/NSCs provide a more powerful autoplastic therapy for the injured
nervous system.
PMID- 24356586
TI - Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity
to suppress hepatitis C virus replication.
AB - First-generation adenovirus vectors (FG AdVs) expressing short-hairpin RNA
(shRNA) effectively downregulate the expressions of target genes. However, this
vector, in fact, expresses not only the transgene product, but also virus
associated RNAs (VA RNAs) that disturb cellular RNAi machinery. We have
established a production method for VA-deleted AdVs lacking expression of VA
RNAs. Here, we showed that the highest shRNA activity was obtained when the shRNA
was inserted not at the popularly used E1 site, but at the E4 site. We then
compared the activities of shRNAs against hepatitis C virus (HCV) expressed from
VA-deleted AdVs or conventional AdVs. The VA-deleted AdVs inhibited HCV
production much more efficiently. Therefore, VA-deleted AdVs were more effective
than the currently used AdVs for shRNA downregulation, probably because of the
lack of competition between VA RNAs and the shRNAs. These VA-deleted AdVs might
enable more effective gene therapies for chronic hepatitis C.
PMID- 24356587
TI - MiR-193b and miR-365-1 are not required for the development and function of brown
fat in the mouse.
AB - Generating heat and maintaining body temperature is the primary function of brown
adipose tissue (BAT). Previous studies have implicated microRNAs, including miR
193b and miR-365-1, in BAT differentiation. We used mouse genetics to further
understand the specific contributions of these two miRs. BAT function in mice
with an inactivated miR-193b-365-1 locus, as determined by their response to the
selective beta3 adrenergic receptor agonist CL316.243 and their tolerance to cold
exposure, was normal and expression of genes associated with functional BAT,
including Prdm16 and Ucp1, was unaffected. In addition, genome-wide expression
profiles of miRNAs and mRNAs in BAT in the presence and absence of miR-193b-365-1
were determined. In summary, these data demonstrate, in contrast to earlier work,
that the development, differentiation, and function of BAT do not require the
presence of miR-193b and miR-365-1.
PMID- 24356589
TI - Self-mixed/split insulin regimen: a serious omission in the ADA/EASD position
statement.
PMID- 24356590
TI - The diabetes control and complications trial/epidemiology of diabetes
interventions and complications study at 30 years: the "gift" that keeps on
giving!
PMID- 24356591
TI - The diabetes control and complications trial/epidemiology of diabetes
interventions and complications study: 30th anniversary presentations.
PMID- 24356592
TI - The diabetes control and complications trial/epidemiology of diabetes
interventions and complications study at 30 years: overview.
AB - OBJECTIVE The Diabetes Control and Complications Trial (DCCT) was designed to
test the glucose hypothesis and determine whether the complications of type 1
diabetes (T1DM) could be prevented or delayed. The Epidemiology of Diabetes
Interventions and Complications (EDIC) observational follow-up determined the
durability of the DCCT effects on the more-advanced stages of diabetes
complications including cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS
The DCCT (1982-1993) was a controlled clinical trial in 1,441 subjects with T1DM
comparing intensive therapy (INT), aimed at achieving levels of glycemia as close
to the nondiabetic range as safely possible, with conventional therapy (CON),
which aimed to maintain safe asymptomatic glucose control. INT utilized three or
more daily insulin injections or insulin pump therapy guided by self-monitored
glucose. EDIC (1994-present) is an observational study of the DCCT cohort.
RESULTS The DCCT followed >99% of the cohort for a mean of 6.5 years and
demonstrated a 35-76% reduction in the early stages of microvascular disease with
INT, with a median HbA1c of 7%, compared with CONV, with a median HbA1c of 9%.
The major adverse effect of INT was a threefold increased risk of hypoglycemia,
which was not associated with a decline in cognitive function or quality of life.
EDIC showed a durable effect of initial assigned therapies despite a loss of the
glycemic separation (metabolic memory) and demonstrated that the reduction in
early-stage complications during the DCCT translated into substantial reductions
in severe complications and CVD. CONCLUSIONS DCCT/EDIC has demonstrated the
effectiveness of INT in reducing the long-term complications of T1DM and
improving the prospects for a healthy life span.
PMID- 24356593
TI - Diabetic retinopathy and other ocular findings in the diabetes control and
complications trial/epidemiology of diabetes interventions and complications
study.
AB - OBJECTIVE To evaluate whether intensive treatment (INT) with the goal of
achieving blood glucose levels as close to the nondiabetic range as safely
possible reduced the risk of onset and progression of diabetic retinopathy (DR)
in subjects with type 1 diabetes (T1D) compared with conventional therapy (CON).
RESEARCH DESIGN AND METHODS The Diabetes Control and Complications Trial (DCCT)
(1982-1993) was a multicenter, controlled clinical trial comparing INT with CON
for onset and progression of DR. The Epidemiology of Diabetes Interventions and
Complications (EDIC) study (1994-present) is an observational follow-up of the
DCCT cohort. RESULTS Of the 1,441 DCCT subjects, 726 had no DR (primary
prevention cohort) and 715 had mild DR (secondary intervention cohort) at
baseline. Subjects were followed for a mean of 6.5 years. INT median HbA1c was 7%
compared with CON median of 9%. INT reduced the adjusted mean risk for the
development of DR by 76% and slowed progression of DR by 54% compared with CON.
Following DCCT, the HbA1c levels in the original INT and CON groups converged
(year 8, INT 7.98%; CON 8.07%); nevertheless, the groups continued to have a
durable effect of initial assigned therapy with significantly lower incidence of
further DR progression in the INT group (hazard reduction 53-56%). Severe retinal
outcomes and procedures to treat them were reduced by 50% in the original INT
group. CONCLUSIONS INT delays the onset and slows the progression of DR.
Furthermore, the early effects of metabolic control continue to accrue over many
years despite subsequent comparable glycemic control (metabolic memory). These
results emphasize the need for optimizing glycemic control as early as possible
in patients with diabetes.
PMID- 24356594
TI - Kidney disease and related findings in the diabetes control and complications
trial/epidemiology of diabetes interventions and complications study.
AB - OBJECTIVE Kidney disease manifests clinically as elevated albumin excretion rate
(AER), impaired glomerular filtration rate (GFR), or both, and is a cause of
substantial morbidity and mortality in type 1 diabetes (T1D). The Diabetes
Control and Complications Trial/Epidemiology of Diabetes Interventions and
Complications (DCCT/EDIC) study tested whether intensive diabetes therapy (INT)
aimed at lowering glucose concentrations as close as safely possible to the
normal range reduces the risks of kidney disease and other diabetes
complications. RESEARCH DESIGN AND METHODS In the DCCT, 1,441 participants with
T1D were randomly assigned to INT or conventional diabetes therapy (CON) for a
mean duration of 6.5 years. Subsequently, participants have been followed for 18
years in the ongoing observational EDIC. Standardized longitudinal measurements
of AER, estimated GFR, and blood pressure were made throughout the DCCT/EDIC.
RESULTS During the DCCT, INT reduced the risks of incident microalbuminuria (AER
>=40 mg/24 h) and macroalbuminuria (AER >=300 mg/24 h) by 39% (95% CI 21-52%) and
54% (29-74%), respectively. During EDIC years 1-8, participants previously
assigned to DCCT INT continued to experience lower rates of incident
microalbuminuria and macroalbuminuria, with risk reductions of 59% (39-73%) and
84% (67-92%), respectively. Beneficial effects of INT on the development of
impaired GFR (sustained estimated GFR <60 mL/min/1.73 m(2)) and hypertension
became evident during combined DCCT/EDIC follow-up, with risk reductions of 50%
(18-69%) and 20% (6-21%), respectively, compared with CON. CONCLUSIONS In the
DCCT/EDIC, INT resulted in clinically important, durable reductions in the risks
of microalbuminuria, macroalbuminuria, impaired GFR, and hypertension.
PMID- 24356595
TI - Neuropathy and related findings in the diabetes control and complications
trial/epidemiology of diabetes interventions and complications study.
AB - OBJECTIVE To describe the development and progression of neuropathy and related
findings among patients with type 1 diabetes who participated in the Diabetes
Control and Complications Trial/Epidemiology of Diabetes Interventions and
Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS The main diabetic
peripheral neuropathy (DPN) outcome was assessed using clinical symptoms, signs,
and nerve conduction study results during DCCT and repeated in EDIC year 13/14.
Cardiovascular autonomic neuropathy (CAN) was assessed by R-R response to paced
breathing, Valsalva ratio, and blood pressure response to standing during DCCT
and in EDIC years 13/14 and 16/17. Additionally, symptoms reflecting neuropathic
pain and autonomic function (including hypoglycemia awareness) were collected
yearly in EDIC using standardized questionnaires; peripheral neuropathy was also
assessed annually using the Michigan Neuropathy Screening Instrument. Assessments
of genitourinary function were collected at EDIC year 10. RESULTS Intensive
therapy during the DCCT significantly reduced the risk of DPN and CAN at DCCT
closeout (64% and 45%, respectively, P < 0.01). The prevalence and incidence of
DPN and CAN remained significantly lower in the DCCT intensive therapy group
compared with the DCCT conventional therapy group through EDIC year 13/14.
CONCLUSIONS The persistent effects of prior intensive therapy on neuropathy
measures through 14 years of EDIC largely mirror those observed for other
diabetes complications. DCCT/EDIC provides important information on the influence
of glycemic control, and the clinical course of diabetic neuropathy, and, most
important, on how to prevent neuropathy in type 1 diabetes.
PMID- 24356596
TI - Update on cardiovascular outcomes at 30 years of the diabetes control and
complications trial/epidemiology of diabetes interventions and complications
study.
AB - OBJECTIVE To describe the beneficial long-term effects of an average of 6.5 years
of intensive diabetes therapy (INT) in type 1 diabetes on measures of
atherosclerosis, cardiac structure and function, and clinical cardiovascular
events observed in the Diabetes Control and Complications Trial (DCCT) and the
Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH
DESIGN AND METHODS The DCCT was a randomized clinical trial of 1,441 participants
assigned to receive INT or conventional therapy (CON). It was conducted between
1983-1993 with an average follow-up of 6.5 years. EDIC (1994-present) is an
observational follow-up of the DCCT cohort. Cardiovascular events have been
recorded throughout. During EDIC common carotid intima-media thickness (IMT) was
measured with ultrasound, coronary artery calcification with computed tomography,
and cardiac structure and function with cardiac magnetic resonance imaging.
RESULTS DCCT INT and lower levels of HbA1c during DCCT/EDIC were associated with
thinner carotid IMT, less coronary calcification, and a lower incidence of
clinical cardiovascular events including myocardial infarction, stroke, and
cardiac death. While there were no significant differences in cardiac structure
and function between the former INT and CON groups, they were significantly
associated with higher HbA1c during DCCT/EDIC. CONCLUSIONS DCCT INT and the
attendant 6.5 years of lower HbA1c had long-term salutary effects on the
development and progression of atherosclerosis and cardiovascular disease during
the subsequent follow-up during EDIC.
PMID- 24356597
TI - The diabetes control and complications trial/epidemiology of diabetes
interventions and complications study at 30 years: summary and future directions.
AB - OBJECTIVE The Diabetes Control and Complications Trial/Epidemiology of Diabetes
Interventions and Complications (DCCT/EDIC) study continues to address knowledge
gaps in our understanding of type 1 diabetes and the effects of intensive therapy
on its long-term complications. RESEARCH DESIGN AND METHODS During the DCCT (1982
1993), a controlled clinical trial of 1,441 subjects with type 1 diabetes, and
the EDIC (1994-present), an observational study of the DCCT cohort, core data
collection has included medical history questionnaires, surveillance health
exams, and frequent laboratory and other evaluations for microvascular and
macrovascular disease. Numerous collaborations have expanded the outcome data
with more detailed investigations of cardiovascular disease, cognitive function,
neuropathy, genetics, and potential biological pathways involved in the
development of complications. RESULTS The longitudinal follow-up of the DCCT/EDIC
cohort provides the opportunity to continue monitoring the durability of
intensive treatment as well as to address lingering questions in type 1 diabetes
research. Future planned analyses will address the onset and progression of
microvascular triopathy, evidence-based screening for retinopathy and
nephropathy, effects of glycemic variability and nonglycemic risk factors on
outcomes, long-term impact of intensive therapy on cognitive decline, and health
economics. Three new proposed investigations include an examination of residual C
peptide secretion and its impact, prevalence of hearing impairment, and
evaluation of gastrointestinal dysfunction. CONCLUSIONS With the comprehensive
data collection and the remarkable participant retention over 30 years, the
DCCT/EDIC continues as an irreplaceable resource for understanding type 1
diabetes and its long-term complications.
PMID- 24356600
TI - Very-low-calorie diet increases myocardial triglyceride content and decreases
diastolic left ventricular function in type 2 diabetes with cardiac
complications.
PMID- 24356598
TI - Prospective study on the incidences of cardiovascular-renal complications in
Chinese patients with young-onset type 1 and type 2 diabetes.
AB - OBJECTIVE We examined metabolic profiles and cardiovascular-renal outcomes in a
prospective cohort of Chinese patients with young-onset diabetes defined by
diagnosis age <40 years. Patients with type 1 diabetes and normal-weight (BMI <23
kg/m(2)) and overweight (BMI >=23 kg/m(2)) patients with type 2 diabetes were
compared. RESEARCH DESIGN AND METHODS Between 1995 and 2004, 2,323 patients (type
1 diabetes, n = 209; normal-weight type 2 diabetes, n = 636; and overweight type
2 diabetes, n = 1,478) underwent detailed clinical assessment. Incident
cardiovascular disease (CVD) including coronary heart disease, stroke, and
peripheral vascular disease were identified using hospital discharge diagnoses.
End-stage renal disease (ESRD) was defined by glomerular filtration rate <15
mL/min/1.73 m(2) or dialysis. RESULTS Overweight patients with type 2 diabetes
had the worst metabolic profile and highest prevalence of microvascular
complications. Over a median follow-up of 9.3 years, incidences of CVD were 0.6,
5.1, and 9.6 per 1,000 person-years in patients with type 1 diabetes, normal
weight patients with type 2 diabetes, and overweight patients with type 2
diabetes. The respective figures for ESRD were 2.2, 6.4, and 8.4 per 1,000 person
years. Compared with type 1 diabetes, the overweight type 2 diabetes group had a
greater hazard of progression to CVD (hazard ratio [HR] 15.3 [95% CI 2.1-112.4])
and ESRD (HR 5.4 [95% CI 1.8-15.9]), adjusted for age, sex, and disease duration.
The association became nonsignificant upon additional adjustment for BMI, blood
pressure, and lipid. CONCLUSIONS Young patients with type 2 diabetes had greater
risks of developing cardiovascular-renal complications compared with patients
with type 1 diabetes. The increased risk was driven primarily by accompanying
metabolic risk factors.
PMID- 24356601
TI - C-peptide levels in latent autoimmune diabetes in adults treated with linagliptin
versus glimepiride: exploratory results from a 2-year double-blind, randomized,
controlled study.
PMID- 24356602
TI - Personal health record design: qualitative exploration of issues inhibiting
optimal use.
PMID- 24356603
TI - Raised circulating fetuin-a after 28-day overfeeding in healthy humans.
PMID- 24356604
TI - Prevalence of muscle cramps in patients with diabetes.
PMID- 24356605
TI - Comment on Hong et al. Effects of metformin versus glipizide on cardiovascular
outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes
care 2013;36:1304-1311.
PMID- 24356606
TI - Response to comment on Hong et al. Effects of metformin versus glipizide on
cardiovascular outcomes in patients with type 2 diabetes and coronary artery
disease. Diabetes care 2013;36:1304-1311.
PMID- 24356607
TI - Glycated hemoglobin in 14,850 adolescent blood donors: a pilot screening program.
PMID- 24356608
TI - The association between conventional risk factors and diabetes is weak among
urban Tanzanians.
PMID- 24356609
TI - The ratio of serum eicosapentaenoic acid to arachidonic acid is associated with
renal impairment and diabetic macroangiopathies in elderly patients with type 2
diabetes.
PMID- 24356610
TI - Nationwide survey of prevalence and risk factors for diabetes and prediabetes in
Bangladeshi adults.
PMID- 24356612
TI - The cost of care of systemic lupus erythematosus (SLE) in the UK: annual direct
costs for adult SLE patients with active autoantibody-positive disease.
AB - OBJECTIVES: The aim of the Systemic LUpus Erythematosus Cost of Care In Europe
(LUCIE) study was to evaluate the annual direct medical costs of managing adults
with active autoantibody-positive disease on medication for SLE in secondary
care. This paper presents the UK analyses only. METHODS: A cost-of-illness study
was conducted from the perspective of the National Health Service. Health
resource utilization data were retrieved over a two-year period from four centres
in England and unit cost data were taken from published sources. RESULTS: At
baseline, 86 patients were included, 38 (44.2%) had severe SLE and 48 (55.8%) had
non-severe SLE. The mean (SD) SELENA-SLEDAI score was 7.7 (5.7). The mean (SD)
annual direct medical cost of was estimated at L3231 (L2333) per patient and was
2.2 times higher in patients with severe SLE compared with patients with non
severe SLE (p < 0.001). Multivariate model analyses showed that renal disease
involvement (p = 0.0016) and severe flares (p = 0.0001) were associated with
higher annual direct costs. CONCLUSIONS: Improvement of the overall stability of
SLE and early intervention to minimize the impact of renal disease may be two
approaches to mitigate the long-term direct cost of managing SLE patients in the
UK.
PMID- 24356611
TI - Podocyte injury in pure membranous and proliferative lupus nephritis: distinct
underlying mechanisms of proteinuria?
AB - Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte
injury. Analysis of podocyte biomarkers was performed attempting to identify if
podocyte phenotype is distinct in pure membranous and proliferative LN.
Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial
protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by
immunohistochemistry. Preserved synaptopodin expression was observed in only 10
(19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had
comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean
follow-up of four years there was a tendency toward lower mean levels of
proteinuria in patients with preserved synaptopodin staining (0.26+/-0.23 vs.
0.84+/-0.90 g/24 h, p = 0.05) compared with those with diminished expression.
Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure
membranous. Comparison of podocyte biomarkers demonstrated a predominance of
preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and
nephrin (60%) in the pure membranous group whereas only <10% of the proliferative
showed preserved expression. Our data suggest that in proliferative forms there
seems to occur structural podocyte damage, whereas in the pure membranous the
predominant preserved pattern suggests a dysfunctional podocyte lesion that may
account for the better long-term prognosis of proteinuria outcome.
PMID- 24356613
TI - Extremely hypotrophic newborn of mother with systemic lupus erythematosus and
antiphospholipid syndrome.
AB - The case presented describes a high-risk pregnancy of a woman with systemic lupus
erythematosus (SLE) with multiple lesions of central nervous system (CNS),
vasculitis, secondary epilepsy and antiphospholipid syndrome (APS). At
gestational age 28 weeks and 3 days the pregnancy was urgently terminated via
caesarean section and an extremely hypotrophic immature newborn with a birth
weight of 580 g was born. The high disease activity in the mother at the time of
conception and the histologically proven chronic placental insufficiency due to
APS are presumably the causes for the extensive hypotrophy of the neonate. The
significant comorbidity of the newborn, including respiratory distress syndrome,
bronchopulmonary dysplasia, necrotizing enterocolitis, osteopathy of prematurity,
transient hypothyroidism and hypocortisolism, vesicoureteral reflux, and
hypertonic-hyperexcitation syndrome complicated his three-month stay in NICU. A
positive titre of transplacentally transferred anticardiolipin and anti-beta2
glycoprotein antibody was detected in the child and persisted through the
following 30 months. During the three-year follow-up, significantly delayed
neuropsychological development with microcephaly (-4 SD) and short stature of the
child was observed. Finally, the authors discuss possible causes of
neuropsychological consequences in children of mothers with SLE and APS and
emphasize the need for long-term monitoring and specialized care to improve
development of these children.
PMID- 24356614
TI - Subacute lupus erythematosus during treatment with golimumab for seronegative
rheumatoid arthritis.
AB - We report on a 52-year-old woman with a history of severe seronegative rheumatoid
arthritis. Several conventional therapies and biological therapy with etanercept
and infliximab had been unsuccessful. In 2010 she was given golimumab
subcutaneously at a monthly dose of 50 mg. She had a negative ANA titre. After 16
months of uninterrupted therapy and sustained response, she developed skin
lesions on the upper trunk, back and upper extremities, which worsened on
exposure to the sun. The skin biopsy was compatible with subacute lupus
erythematosus. Laboratory findings included an ANA titre 1:640, negative anti
Ro/SSA and anti-DNA antibodies. Topical corticosteroid therapy proved inadequate.
The patient's condition improved only after discontinuation of golimumab. The
causal relationship between subacute cutaneous lupus erythematosus and golimumab
is not dose-related and occurs with some delay (a typical feature of
immunological adverse reactions). The association is likely, but not confirmed
(because re-challenge was not performed). However, a clear improvement was noted
after withdrawal. Based on this case, we hypothesized the aetiological role of
golimumab-associated immunogenicity. TNF-alpha antagonist-induced lupus-like
syndrome (TAILS) is a well-known side effect of this class of substances. The
British Society of Rheumatology recommends discontinuation of the causal anti-TNF
alpha treatment in patients with TAILS.
PMID- 24356615
TI - Enhanced optical properties and (Zn, Mg) interdiffusion in vapour transport grown
ZnO/MgO core/shell nanowires.
AB - ZnO/MgO (core/shell) nanowires (NWs) grown by a two-step vapour transport method
under different MgO shell growth conditions are examined by x-ray diffraction,
photoluminescence (PL) excitation and temperature (10-300 K) dependent PL. The
excitonic-to-defect PL ratio is increased by more than two orders of magnitude in
the core/shell as compared to bare ZnO NWs. Concomitantly, a strong depression of
the PL thermal quenching, most particularly for the visible part of the PL
spectrum, occurs. Using a semi-quantitative model, results are interpreted as a
strong radiative to non-radiative lifetime ratio reduction due to defect
passivation at the ZnO NW walls and photocarrier confinement within the ZnO core
by the MgO shell. These beneficial effects are, however, significantly weakened
when metal interdiffusion across the core/shell interface is favoured during the
shell growth. Non-radiative recombination lifetime in the sample with sharp
core/shell interface is described by a single activation energy of 15 meV (bound
exciton release). For interdiffused cases and bare ZnO an additional activation
energy of 60 meV (free exciton breakup) is observed.
PMID- 24356617
TI - Annals of Oncology: an editorial perspective.
PMID- 24356618
TI - Accelerated chemotherapy for germ cell cancer.
PMID- 24356619
TI - A critical review of the analytical approaches for circulating tumor biomarker
kinetics during treatment.
AB - Changes in serum tumor biomarkers may indicate treatment efficacy. Traditional
tumor markers may soon be replaced by novel serum biomarkers, such as circulating
tumor cells (CTCs) or circulating tumor nucleic acids. Given their promising
predictive values, studies of their kinetics are warranted. Many methodologies
meant to assess kinetics of traditional marker kinetics during anticancer
treatment have been reported. Here, we review the methodologies, the advantages
and the limitations of the analytical approaches reported in the literature.
Strategies based on a single time point were first used (baseline value,
normalization, nadir, threshold at a time t), followed by approaches based on two
or more time points [half-life (HL), percentage decrease, time-to-events...].
Heterogeneities in methodologies and lack of consideration of inter- and intra
individual variability may account for the inconsistencies and the poor utility
in routine. More recently, strategies based on a population kinetics approach and
mathematical modeling have been reported. The identification of equations
describing individual kinetic profiles of biomarkers may be an alternative
strategy despite its complexity and higher number of necessary measurements.
Validation studies are required. Efforts should be made to standardize biomarker
kinetic analysis methodologies to ensure the optimized development of novel serum
biomarkers and avoid the pitfalls of traditional markers.
PMID- 24356620
TI - Final results from the prospective phase III WSG-ARA trial: impact of adjuvant
darbepoetin alfa on event-free survival in early breast cancer.
AB - BACKGROUND: WSG-ARA plus trial evaluated the effect of adjuvant darbepoetin alfa
(DA) on outcome in node positive primary breast cancer (BC). PATIENTS AND
METHODS: One thousand two hundred thirty-four patients were randomized to
chemotherapy either with DA (DA+; n = 615) or without DA (DA-; n = 619). DA (500
ug q3w) was started at hemoglobin (Hb) levels <13.0 g/dl (<12 g/dl after DA label
amendment) and stopped at Hb levels >=14.0 g/dl (12 g/dl after label amendment).
Primary efficacy end point was event-free survival (EFS); secondary end points
were toxicity, quality of life (QoL) and overall survival (OS). RESULTS: Venous
thrombosis (DA+: 3.0%, DA-: 1.0%; P = 0.013) was significantly higher for DA+,
but not pulmonary embolism (0.3% in both arms). Median Hb levels were stable in
DA+ (12.6 g/dl) and decreased in DA- (11.7 g/dl). Hb levels >15 g/dl were
reported in 0.8% of cycles. QoL parameters did not significantly differ between
arms. At 39 months, DA had no significant impact on EFS (DA+: 89.3%, DA-: 87.5%;
Plog-rank = 0.55) or OS (DA+: 95.5%, DA-: 95.4%; Plog-rank = 0.77). CONCLUSIONS:
DA treatment did not impact EFS or OS in routine adjuvant BC treatment.
PMID- 24356621
TI - Construction of novel immune-related signature for prediction of pathological
complete response to neoadjuvant chemotherapy in human breast cancer.
AB - BACKGROUND: The aim of this study was to construct a novel prediction model for
the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) using
immune-related gene expression data. PATIENTS AND METHODS: DNA microarray data
were used to perform a gene expression analysis of tumor samples obtained before
NAC from 117 primary breast cancer patients. The samples were randomly divided
into the training (n = 58) and the internal validation (n = 59) sets that were
used to construct the prediction model for pCR. The model was further validated
using an external validation set consisting of 901 patients treated with NAC from
six public datasets. RESULTS: The training set was used to construct an immune
related 23-gene signature for NAC (IRSN-23) that is capable of classifying the
patients as either genomically predicted responders (Gp-R) or non-responders (Gp
NR). IRSN-23 was first validated using an internal validation set, and the
results showed that the pCR rate for Gp-R was significantly higher than that
obtained for Gp-NR (38 versus 0%, P = 1.04E-04). The model was then tested using
an external validation set, and this analysis showed that the pCR rate for Gp-R
was also significantly higher (40 versus 11%, P = 4.98E-23). IRSN-23 predicted
pCR regardless of the intrinsic subtypes (PAM50) and chemotherapeutic regimens,
and a multivariate analysis showed that IRSN-23 was the most important predictor
of pCR (odds ratio = 4.6; 95% confidence interval = 2.7-7.7; P = 8.25E-09).
CONCLUSION: The novel prediction model (IRSN-23) constructed with immune-related
genes can predict pCR independently of the intrinsic subtypes and
chemotherapeutic regimens.
PMID- 24356622
TI - Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for
second-line treatment of metastatic colorectal cancer.
AB - BACKGROUND: The study 20050181 demonstrated significant improvements in
progression-free survival (PFS), objective response, and a nonsignificant trend
toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI
alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC).
Updated long-term data from a prespecified descriptive analysis are reported.
PATIENTS AND METHODS: Patients receiving one prior mCRC treatment were randomly
assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks.
Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS
status. RESULTS: One thousand one hundred and eighty-six patients were randomly
assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly
improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82
[95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS
was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P =
0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc
analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI
improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P =
0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0
1 or FOLFIRI. Safety results were as previously reported and consistent with the
known toxicities with anti-epidermal growth factor receptor therapy. CONCLUSIONS:
These data confirm the primary efficacy and safety findings of this trial and
support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.
PMID- 24356623
TI - Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with
concurrent external beam radiation therapy in locally advanced rectal cancer.
AB - BACKGROUND: To determine the maximal tolerated dose of erlotinib when added to 5
fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of
this combination in patients with locally advanced rectal cancer. PATIENTS AND
METHODS: Patients with Magnetic resonance imaging (MRI) or ultrasound defined T3
or T4 adenocarcinoma of the rectum and without evidence of metastatic disease
were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously,
along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was
administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg
orally daily and advanced by 50 mg increments in the subsequent cohort. Open
total mesorectal excision was carried out 6-9 weeks following the completion of
chemoradiation. RESULTS: Thirty-two patients received one of three dose levels of
erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally
tolerated dose. Thirty-one patients underwent resection of the primary tumor, one
refused resection. Twenty-seven patients completed study therapy, all of whom
underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of
patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response
(pCR) for all patients completing study therapy was 33%. With a median follow-up
of 2.9 years, there are no documented local recurrences. Disease-free survival at
3 years is 75.5% (confidence interval: 55.1-87.6%). CONCLUSIONS: Erlotinib added
to infusional 5-FU, bevacizumab and radiation in patients with locally advanced
rectal cancer is relatively well tolerated and associated with an encouraging
pCR.
PMID- 24356624
TI - Randomised phase II study of axitinib or bevacizumab combined with
paclitaxel/carboplatin as first-line therapy for patients with advanced non-small
cell lung cancer.
AB - BACKGROUND: Efficacy and safety of first-line axitinib/paclitaxel/carboplatin
versus bevacizumab/paclitaxel/carboplatin in advanced non-squamous non-small-cell
lung cancer (NSCLC) was evaluated. PATIENTS AND METHODS: Patients with stage
IIIB/IV disease stratified by adjuvant therapy and gender were randomised 1 : 1
to axitinib (5 mg twice daily) or bevacizumab [15 mg/kg every 3 weeks (Q3W)],
both with paclitaxel (200 mg/m(2) Q3W)/carboplatin (AUC 6 mg min/ml Q3W).
RESULTS: The trial was discontinued after preliminary analysis. Median
progression-free survival (primary end point) for axitinib (N = 58) and
bevacizumab (N = 60), respectively, was 5.7 and 6.1 months [hazard ratio (HR)
1.09, 95% confidence interval (CI) 0.68-1.76; one-sided stratified P = 0.64];
median overall survival was 10.6 and 13.3 months (HR 1.12, 95% CI 0.74-1.69; one
sided stratified P = 0.70). Objective response rates (95% CI) were 29.3% (18.1
42.7) and 43.3% (30.6-56.8), respectively; risk ratio 0.676 (95% CI 0.41-1.11;
one-sided stratified P = 0.94). The most common grade 3/4 adverse events included
neutropenia (28% versus 20%), fatigue (14% versus 7%), and hypertension (14%
versus 5%). Patient-reported outcomes based on the EORTC QLQ-C30 were similar
between arms. CONCLUSIONS: In patients with advanced non-squamous NSCLC,
axitinib/paclitaxel/carboplatin did not improve efficacy versus
bevacizumab/paclitaxel/carboplatin, and was less well tolerated.
PMID- 24356625
TI - Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by
the Australian and New Zealand Urogenital and Prostate Cancer Trials Group
(ANZUP).
AB - BACKGROUND: This Australian single-arm, multicenter, phase II trial evaluated
feasibility, tolerability and activity of accelerated bleomycin, etoposide and
cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours.
PATIENTS AND METHODS: Patients were planned to receive cisplatin 20 mg/m(2) and
etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every
2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at
30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end
point was feasibility, defined as the proportion of patients able to complete the
etoposide and cisplatin components of BEP and be eligible to receive a fourth
cycle of BEP by day 50. RESULTS: Twelve poor, 16 intermediate and 15 good
prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years
were ineligible and excluded from analyses. The regimen was feasible in 86%, not
feasible in 7% and not assessable in 7% of patients. Most common grade 3/4
adverse events were non-neutropenic infection (16%) and febrile neutropenia
(12%). Complete response (CR) to chemotherapy and surgery was achieved in 33%
poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At
median follow-up of 27 months (range 6-42), the 2-year progression-free survival
was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good
prognosis patients. CONCLUSION: Accelerated BEP is feasible and tolerable.
Efficacy data appear to be promising. This trial and a similar UK study provide
the rationale for a randomised trial comparing accelerated versus standard BEP.
Australian New Zealand Clinical Trials Registry Registration number. ACTRN
12607000294459.
PMID- 24356627
TI - A cohort study investigating aspirin use and survival in men with prostate
cancer.
AB - BACKGROUND: Aspirin use has been associated with reduced mortality from cancer
including prostate cancer in some studies. A number of anti-cancer mechanisms of
aspirin have been proposed, including the inhibition of the cyclooxygenase
enzymes, through which aspirin mediates both anti-platelet and anti-inflammatory
activities. This cohort study examines associations between pre-diagnostic
aspirin use (overall and by dose and dosing intensity) and mortality in men with
localised prostate cancer. PATIENTS AND METHODS: Men with stage I-III prostate
cancer were identified from Irish National Cancer Registry records, which have
been linked to national prescribing data from the Irish General Medical Services
scheme. Aspirin use in the year preceding prostate cancer diagnosis was
identified from this linked prescription-claims data. Adjusted hazard ratios
(HRs) and 95% confidence intervals (CIs) were estimated for associations between
aspirin use and all-cause and prostate cancer-specific mortality. Associations
between prescribed dose and dosing intensity were examined. The presence of
effect modification by the type of treatment received and tumour characteristics
was also assessed. RESULTS: Two thousand nine hundred and thirty-six men with a
diagnosis of stage I-III prostate cancer (2001-2006) were identified (aspirin
users, n = 1131). The median duration of patient follow-up was 5.5 years. In
adjusted analyses, aspirin use was associated with a small, but non-significant,
reduced risk of prostate cancer-specific mortality (HR = 0.88, 95% CI 0.67-1.15).
In dose-response analyses, stronger associations with prostate cancer-specific
mortality were observed in men with higher aspirin dosing intensity (HR = 0.73,
95% CI 0.51-1.05) and in men receiving >75 mg of aspirin (HR = 0.61, 95% CI 0.37
0.99). Analyses of effect modification by treatment type or tumour
characteristics were non-significant. CONCLUSIONS: Consistent with prior studies,
aspirin use was associated with a non-significant reduced risk of prostate cancer
specific mortality in men with localised prostate cancer. Men receiving higher
doses of aspirin had a statistically significant reduced risk of prostate cancer
specific mortality. These findings regarding an aspirin dose require further
investigation.
PMID- 24356626
TI - Outcomes of patients with metastatic renal cell carcinoma that do not meet
eligibility criteria for clinical trials.
AB - BACKGROUND: Targeted therapies in metastatic renal cell carcinoma (mRCC) have
been approved based on registration clinical trials that have strict eligibility
criteria. The clinical outcomes of patients treated with targeted agents but are
ineligible for trials are unknown. PATIENTS AND METHODS: mRCC patients treated
with vascular endothelial growth factor-targeted therapy were retrospectively
deemed ineligible for clinical trials (according to commonly used
inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS)
<70%, nonclear-cell histology, brain metastases, hemoglobin <=9 g/dl, creatinine
>2* the upper limit of normal, corrected calcium >=12 mg/dl, platelet count of
<100 * 10(3)/uL, or neutrophil count <1500/mm(3). RESULTS: Overall, 768 of 2210
(35%) patients in the International Metastatic RCC Database Consortium (IMDC)
were deemed ineligible for clinical trials by the above criteria. Between
ineligible versus eligible patients, the response rate, median progression-free
survival (PFS) and median overall survival of first-line targeted therapy were
22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months
(both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months
in the trial ineligible versus 4.3 months in the trial eligible patients (P =
0.0039). When adjusted by the IMDC prognostic categories, the HR for death
between trial ineligible and trial eligible patients was 1.55 (95% confidence
interval 1.378-1.751, P < 0.0001). CONCLUSIONS: The number of patients that are
ineligible for clinical trials is substantial and their outcomes are inferior.
Specific trials addressing the unmet needs of protocol ineligible patients are
warranted.
PMID- 24356628
TI - The impact of activated p-AKT expression on clinical outcomes in diffuse large B
cell lymphoma: a clinicopathological study of 262 cases.
AB - BACKGROUND: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase
(PI3K/AKT) pathway plays a critical role in cell proliferation and growth.
Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and
to have poor prognostic impact in solid tumors. PATIENTS AND METHODS: To define
the clinical implications of p-AKT expression in diffuse large B-cell lymphoma
(DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the
proportion of p-AKT expression and investigated the impact of p-AKT expression on
clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value
of the upper limit of the third quartile of AUs, 56 patients were classified as
high p-AKT and the remaining 206 patients were classified as low p-AKT. RESULTS:
The high p-AKT group was closely associated with more advanced stage (stage III
IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic
dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk
groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P =
0.01). The high p-AKT group showed substantially worse overall survival (OS)
(median OS, 115.0 months versus not reached, P = 0.004) and progression-free
survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with
the low p-AKT group. Multivariate analysis revealed that high p-AKT expression
retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95%
confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression
and concurrent Epstein-Barr virus positivity showed worst prognosis with the
median OS and PFS of 15.2 and 7.4 months. CONCLUSION: DLBCL patients with high p
AKT expression showed distinct clinical features and followed a more rapidly
deteriorating clinical course with worse OS and PFS. Thus, a more effective
treatment option should be developed for this subset of DLBCL patients, and
targeting PI3K/AKT pathway may be a promising therapeutic strategy.
PMID- 24356629
TI - Autologous stem cell transplantation for elderly patients with newly diagnosed
multiple myeloma in the era of novel agents.
AB - BACKGROUND: High-dose therapy (HDT) with autologous stem cell transplantation
(ASCT) is considered the standard of care for multiple myeloma (MM) patients <65
years. Safety and outcome of ASCT for patients >65 years is currently uncertain,
especially since the introduction of novel agents for induction and maintenance
therapy. Furthermore, there are no conclusive data available on risk assessment
in elderly patients treated with HDT. PATIENTS AND METHODS: We retrospectively
analyzed 202 patients >=60 years with newly diagnosed MM who underwent ASCT at
our institution. Patients were stratified by age into three groups (60-64, 65-69
and 70-75 years). For safety assessment, we compared data about hospitalization,
hematopoetic reconstitution and early mortality. Remission before and after ASCT
was analyzed according to age and application of novel agents. Event-free (EFS)
and overall survival (OS) were analyzed to identify impact of age, remission
before/after ASCT and maintenance therapy as well as ISS score and cytogenetic
aberrations on outcome in elderly patients. RESULTS: The assessment of safety,
remission before/after ASCT as well as EFS and OS showed no significant
differences between the three groups (median EFS: 60-64 years: 27 months; 65-69
years: 23 months; 70-75 years: 23 months; median OS: not reached). Patients
receiving novel agents as part of induction therapy achieved significantly higher
nCR + CR rates than patients treated without novel agents. In Cox regression
analysis, ISS and cytogenetics as well as remission after ASCT had the highest
prognostic impact on EFS and OS. Maintenance therapy was associated with longer
EFS in uni- and multivariate analyses. CONCLUSION: ASCT is feasible for selected
patients >65 and >70 years without increased mortality. Age at transplantation
has no prognostic significance on outcome after ASCT. Novel agents during
induction therapy and maintenance therapy improves outcome of older patients
eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely
for risk assessment.
PMID- 24356630
TI - Significant improvement in the survival of patients with multiple myeloma
presenting with severe renal impairment after the introduction of novel agents.
AB - BACKGROUND: Renal impairment (RI) is a common presenting complication of multiple
myeloma (MM); the availability of new treatments has improved the outcomes of
patients with MM; however, their impact on the survival of patients who present
with RI has not been extensively studied. PATIENTS AND METHODS: We analyzed the
characteristics and outcomes of 1773 consecutive unselected patients who were
treated for symptomatic myeloma since January 1990. RESULTS: Although there was a
significant increase in the proportion of patients of advanced age in the more
recent periods, the frequency of RI as well as the proportion of patients who
presented with severe RI (eGFR < 30 ml/min/1.73 m(2)) remained unchanged around
18%. Thus, after adjustment for age, there was a decrease in the risk of severe
RI at presentation after 2000. Myeloma response rates (>=PR) to frontline therapy
have substantially increased, and this was translated in a significant increase
in the median survival. Specifically for patients with severe RI, the median OS
has improved from 18 and 19.5 months in the 1990-1994 and 1995-1999 to 29 and 32
months for the periods 2000-2004 and after 2005 (P = 0.005). Severe RI was
associated with a high risk of early death (12% versus 7% for patients with
moderate RI versus 3% for patients with mild or no RI (P < 0.001), especially
among older patients, and has remained unchanged over time. CONCLUSIONS: There
has been a major improvement in the survival of patients with severe RI in the
past decade, despite the increasing numbers of patients of advanced age. However,
the risk of early death remains high in patients with severe RI, especially in
the elderly.
PMID- 24356631
TI - The impact of allogeneic stem cell transplantation on the natural course of poor
risk chronic lymphocytic leukemia as defined by the EBMT consensus criteria: a
retrospective donor versus no donor comparison.
AB - BACKGROUND: In a single-center retrospective donor versus no-donor comparison, we
investigated if allogeneic stem cell transplantation (alloSCT) can improve the
dismal course of poor-risk chronic lymphocytic leukemia (CLL). PATIENTS AND
METHODS: All patients with CLL who were referred for evaluation of alloSCT within
a 7-year time frame and had a donor search indication according to the EBMT
criteria or because of Richter's transformation were included. Patients for whom
a matched donor could be found within 3 months (matches) were compared with
patients without such a donor (controls). Primary end point was overall survival
measured from the 3-month landmark after search initiation. RESULTS: Of 105
patients with donor search, 97 (matches 83; controls 14) were assessable at the 3
month landmark. Matches and controls were comparable for age, gender, time from
diagnosis, number of previous regimens, and remission status. Disregarding if
alloSCT was actually carried out or not, survival from the 3-month landmark was
significantly better in matches versus controls [hazard ratio 0.38, 95%
confidence interval (CI) 0.17-0.85; P = 0.014]. The survival benefit of matches
remained significant on multivariate analysis. CONCLUSION: This study provides
first comparative evidence that alloSCT may have the potential to improve the
natural course of poor-risk CLL as defined by the EBMT criteria.
PMID- 24356632
TI - Transformation and additional malignancies are leading risk factors for an
adverse course of disease in marginal zone lymphoma.
AB - BACKGROUND: Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as
extra nodal, nodal, or splenic. While MZL is generally considered an indolent
disease, a substantial percentage of patients follow an unfavorable course. The
objective of this retrospective analysis was to identify predictors for a reduced
overall survival (OS), or conversely an increased OS. PATIENTS AND METHODS: One
hundred and ninety-seven MZL patients were analyzed. Apart from assessing
previously published risk factors, concomitant morbidity at diagnosis,
transformation into aggressive lymphoma, and occurrence of additional
malignancies were evaluated. RESULTS: Next to the known risk factors, i.e. above
60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate
that transformation into aggressive lymphoma, as well as additional malignancies,
are important independent risk factors for a shortened OS in a multivariate
analysis, irrespective of the MZL localization. Impressively, in the group of
patients lacking LDH elevation, transformation, and/or additional malignancies,
only 1 of 63 patients died during follow-up compared with 37 of 87 patients in
the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002).
CONCLUSIONS: Our analysis proposes novel risk factors and warrants for a
continuous follow-up to detect the occurrence of transformation and additional
malignancies early on.
PMID- 24356633
TI - Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis
from North American and European cooperative groups.
AB - BACKGROUND: Parameningeal (PM) site is a well-known adverse prognostic factor in
children with localized rhabdomyosarcoma (RMS). To identify risk factors
associated with outcome at this site, we pooled data from 1105 patients treated
in 10 studies conducted by European and North American cooperative groups between
1984 and 2004. PATIENTS AND METHODS: Clinical factors including age, histology,
size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS)
clinical group, site, risk factors for meningeal involvement (MI), study group,
and application of radiotherapy (RT) were studied for their impact on event-free
and overall survival (EFS and OS). RESULTS: Ten-year EFS and OS were 62.6 and
66.1% for the whole group. Patients without initial RT showed worse survival (10
year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis
focusing on 862 patients who received RT as part of their initial treatment
revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI,
unfavorable site, and tumor size. Utilizing these prognostic factors, patients
could be classified into different risk groups with 10-year OS ranging between
51.1 and 80.9%. CONCLUSIONS: While, in general, PM localization is regarded as an
adverse prognostic factor, the current analysis differentiates those with good
prognosis (36% patients with 0-1 risk factor: 10-year OS 80.9%) from high-risk PM
patients (28% with 3-4 factors: 10-year OS 51.1%). Furthermore, this analysis
reinforces the necessity for RT in PM RMS.
PMID- 24356634
TI - A multicenter phase II study of pazopanib in patients with advanced
gastrointestinal stromal tumors (GIST) following failure of at least imatinib and
sunitinib.
AB - BACKGROUND: Advanced GISTs are incurable, but often treatable for years with
tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic
activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with
TKIs most often leads to durable disease control for many patients. However,
almost all patients develop resistance to these TKIs, typically due to the
development of secondary mutations, heralding the need for new therapeutic
options. We conducted a phase II study evaluating the efficacy and toxicity of
pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and
PDGFR (-alpha and-beta) in patients with advanced GIST following failure of at
least imatinib and sunitinib. METHODS: Patients received pazopanib 800 mg orally
once daily. All patients were assessed for efficacy with CT scans every 8 weeks
(two cycles). Patients continued pazopanib until progression or unacceptable
toxicity. The primary end point was the 24-week nonprogression [complete
response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1.
Secondary end points included PFS, OS, and toxicity. RESULTS: Between August 2011
and September 2012, a total of 25 patients were treated at two institutions.
Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of
pazopanib were administered, with a median of two cycles (range 1 to 17+) per
patient. Best response of SD at any time was observed in 12 (48%) patients. The
NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient
discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One
patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing
disease control after 17 cycles. The median PFS for the entire cohort was 1.9
months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR).
CONCLUSIONS: Pazopanib was reasonably well tolerated with no unexpected
toxicities. Pazopanib as a single agent has marginal activity in unselected
heavily pretreated patients with advanced GIST.
PMID- 24356635
TI - The number of excised lymph nodes is associated with survival of melanoma
patients with lymph node metastasis.
AB - BACKGROUND: Although the number of excised LNs has been associated with patient
prognosis in many solid tumors, this association has not been widely investigated
in cutaneous melanoma. This study aims to evaluate the association between the
number of excised regional lymph nodes (LNs) and melanoma-specific survival.
PATIENT AND METHODS: Clinico-pathological data from 2507 patients with LN
metastasis treated at nine Italian centers were retrospectively collected.
RESULTS: The number of excised LNs correlated with younger age (P < 0.001), male
sex (P < 0.001), neck LN field (P < 0.001), LN micrometastasis (P < 0.001) and
number of positive LNs (P < 0.001). The number of excised LNs was an independent
prognostic factor (HR = 0.85; P = 0.002) after adjustment for other staging
features. Upon subgroup analysis, the number of excised LNs had a significant
prognostic value in patients bearing 1.01-2.00 mm (HR = 0.79; P = 0.032) and 2.01
4.00 mm (HR = 0.71; P < 0.001) thick melanomas, primary tumors showing ulceration
(HR = 0.86; P = 0.033) and Clark level V of invasion (HR = 0.86; P = 0.010), LN
micrometastasis (HR = 0.83; P = 0.014) and two to three positive LNs (HR = 0.71;
P = 0.001). Finally, this study investigated the influence of the number of
excised LNs on patient staging: only when >=11 nodes were excised the AJCC N
stage could stratify prognosis (P < 0.001). Considering the number of excised LNs
for each lymphatic field, at least 14, 11, 10 and 12 LNs were needed to stage
patients according to the AJCC N stage after a lymphadenectomy of the neck,
axilla, inguinal and ilioinguinal LN fields, respectively. CONCLUSIONS: The
number of excised LNs can be considered for risk stratification of patients with
regional LN metastasis from cutaneous melanoma. We demonstrated that a minimum
number of LNs is required for the correct staging of patients. Further research
is needed to evaluate the effectiveness of the minimum number of LNs to be
dissected.
PMID- 24356636
TI - Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly
paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin
as a first-line treatment for stage II-IV ovarian cancer: Japanese Gynecologic
Oncology Group Trial (JGOG3016).
AB - BACKGROUND: Dose-dense weekly paclitaxel (Taxol) and carboplatin (dd-TC) improved
survival compared with conventional tri-weekly paclitaxel and carboplatin (c-TC)
as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in
the Japanese Gynecologic Oncology Group 3016 trial. We report the quality-of-life
(QoL) results from this trial. PATIENTS AND METHODS: A total of 637 patients were
randomly assigned to receive c-TC or dd-TC (c-TC, n = 319; dd-TC, n = 312) and
were asked to complete a QoL assessment at baseline, just after the third and
sixth chemotherapy cycles, and at 12 months after randomization. QoL was assessed
using Functional Assessment of Cancer Therapy (FACT)-general (FACT-G), FACT
taxane subscale (FACT-T), and FACT-ovary subscale (FACT-Ov). The overall QoL and
that according to each subscale were analyzed using mixed-effects models adjusted
for treatment and time. RESULTS: Baseline QoL assessment was completed by 204 out
of 319 (63.9%) and 200 out of 312 (64.1%) patients in the c-TC and dd-TC groups,
respectively. In these groups, the compliance rates with regard to QoL assessment
were 74.5% and 73.0%, respectively, after three chemotherapy cycles; 86.8% and
86.9%, respectively, after six chemotherapy cycles; and 74.2% and 71.6%,
respectively, at 12 months after randomization. The overall QoL did not differ
significantly between the two treatment groups up to 12 months after
randomization (P = 0.46). However, QoL according to the FACT-T subscale was
significantly lower in the dd-TC group than in the c-TC group (P = 0.02).
CONCLUSION: dd-TC does not decrease overall QoL compared with c-TC.
PMID- 24356637
TI - How do the EMA and FDA decide which anticancer drugs make it to the market? A
comparative qualitative study on decision makers' views.
AB - BACKGROUND: The process leading to a regulatory outcome is guided by factors both
related and unrelated to the data package, defined in this analysis as 'formal
and informal factors', respectively. The aim of this qualitative study was to
analyse which formal and informal factors drive the decision-making process of
the European Medicines Agency (EMA) and Food and Drug Administration (FDA)
regulators with regard to anticancer drugs, using in-depth semi-structured
interviews with regulators of the two agencies. METHODS: In line with the theory
and practice of qualitative research, no set sample size was defined a priori.
Respondent enrolment continued until saturation and redundancy were reached. Data
were collected through means of in-depth semi-structured interviews conducted
either in a face-to-face setting or via Skype((r)) with each regulator. The
interviews were audio-recorded and verbatim transcribed. The analysis was
manually carried out on the transcribed text. Data were independently coded and
categorized by two researchers. Interpretation of the findings emerged through a
process of triangulation between the two. RESULTS: Seven EMA and six FDA
regulators, who had extensive experience with making decisions about anticancer
medicines, were interviewed between April and June 2012. There is an open
dialogue between the FDA and EMA, with the two moving closer and exchanging
information, not opinions. Differences in decision-making between the agencies
may be due to a different evaluation of end points. Different interaction
modalities with industry and patients represent an additional source of
divergence with a potential impact on decision-making. The key message of our
respondents was that the agencies manage uncertainty in a different way: unlike
the EMA, the FDA has a prevailing attitude to take risks in order to guarantee
quicker access to new treatments. CONCLUSIONS: Although formal factors are the
main drivers for regulatory decisions, the influence of informal factors plays an
important role in the drug evaluation process.
PMID- 24356638
TI - Selection of oncology medicines in low- and middle-income countries.
AB - BACKGROUND: High cancer mortality rates in low- and middle-income countries
(LMICs) have raised concerns regarding access to oncology medicines. Essential
medicines are those which satisfy the primary health care needs and provide a
basis for public procurement or reimbursement decisions in LMICs. We explored
selection of oncology medicines in LMICs through investigating national essential
medicines lists (NEMLs) for cancer treatments. METHODS: Recently updated NEMLs
were retrieved for 76 countries. Oncology medicines were classified based on
therapeutic categories. Countries were clustered based on geographic regions,
income levels and burden of cancer (mortality and morbidity). Indicators of
frequency (number of medicines), diversity (number of therapeutic
(sub)categories) and more importantly absence were measured and compared across
countries using parametric and nonparametric tests. RESULTS: The overall median
number of oncology medicines on NEMLs was 16 (interquartile range = 23) chosen
predominantly from subcategories of 'antineoplastic agents', with substantial
variation across regions and income groups. Five countries did not select any
oncology medicine and 68% did not have any 'hormones and related agents' on their
NEMLs. Newer technologies like targeted therapies were infrequently incorporated.
The cluster of countries suffering most from the burden of cancer selected more
essential oncology medicines and diversified further. CONCLUSION: The observed
selection of oncology essential medicines can reflect insufficiencies and
inequalities in access to cancer treatments at least in the public sector of
LMICs. Further resources need to be allocated from governments and international
organizations to tackle the problem of access to oncology medicines in these
countries.
PMID- 24356640
TI - Patterns and trends in esophageal cancer mortality and incidence in Europe (1980
2011) and predictions to 2015.
AB - BACKGROUND: Over the last few decades, esophageal cancer incidence and mortality
trends varied substantially across Europe, with important differences between
sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and
adenocarcinoma (EAC). PATIENTS AND METHODS: To monitor recent esophageal cancer
mortality trends and to compute short-term predictions in the European Union (EU)
and selected European countries, we analyzed data provided by the World Health
Organization (WHO) for 1980-2011. We also analyzed incidence trends and relative
weights of ESCC and EAC across Europe using data from Cancer Incidence in Five
Continents. RESULTS: Long-term decreasing trends were observed for male
esophageal cancer mortality in several southern and western European countries,
whereas in central Europe mortality increased until the mid-1990s and started to
stabilize or decline over the last years. In some eastern and northern countries,
the rates were still increasing. Mortality among European women remained
comparatively low and showed stable or decreasing trends in most countries.
Between 2000-2004 and 2005-2009, esophageal cancer mortality declined by 7% (from
5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU
women. Predictions to 2015 show persistent declines in mortality rates for men in
the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000
men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern
Europe, EAC is now the predominant histological type among men, while for
European women ESCC is more common and corresponding rates are still increasing
in several countries. CONCLUSION(S): The observed trends reflect the variations
in alcohol drinking, tobacco smoking and overweight across European countries.
PMID- 24356639
TI - The prognostic significance of left ventricular ejection fraction in patients
with advanced cancer treated in phase I clinical trials.
AB - BACKGROUND: New targeted agents may cause acute cardiac events. The purpose of
our study was to investigate the incidence and the prognostic significance of
left ventricular ejection fraction (LVEF) in phase I trials. PATIENTS AND
METHODS: Between October 2008 and September 2011, the records of 1166 consecutive
patients with advanced cancer treated in the Phase I Clinic who underwent
echocardiography were retrospectively reviewed. RESULTS: Most of the patients
were White (78%), and the most common tumor types were colorectal cancer and
melanoma. Of 1166 patients, 177 (15.2%) patients had an LVEF of <50%. No
difference in overall survival (OS) between patients with LVEF >= 50% and
patients with LVEF < 50% was seen (median OS 7.4 versus 7.0 months, P = 0.84).
Patients with LVEF <= 35% had shorter survival compared with those with LVEF
between 35% and 50% (median 4.2 versus 8.0 months; P = 0.005). In multivariate
analysis of patients with LVEF < 50%, independent factors predicting longer
survival were LVEF > 35%, <=2 prior systemic therapies, <=2 metastatic sites, and
normal lactate dehydrogenase and albumin levels. CONCLUSION: Echocardiography
would improve patient selection for enrollment in phase I clinical trials. These
data suggest that it is safe to treat patients with LVEF between 35% and 50%.
PMID- 24356642
TI - Concurrent unilateral or bilateral native nephrectomy in kidney transplant
recipients.
AB - BACKGROUND: The aim of this study is to present results of patients who have
undergone renal transplantation concurrent with bilateral or unilateral native
nephrectomy, with a special focus on polycystic kidney disease (PKD). MATERIAL
AND METHODS: We presented the outcome of renal transplantation patients who have
undergone native nephrectomy unilaterally (n=38) and bilaterally (n=125) and
compared the results of patients with PKD and other nephrectomy indications.
RESULTS: Overall graft survival in the 1st, 3rd, and 5th years were 93%, 90%, and
89%, respectively, in transplantation with concomitant nephrectomy patients.
Overall patient survival in the 1st, 3rd, and 5th years were 97%, 94%, and 94%,
respectively. Overall surgical complications rate was 17.7% and medical
complication rate was 19%. Patients with PKD had more frequent complications.
CONCLUSIONS: Despite additional surgery, the long-term results of patients with
complications were not affected negatively by early diagnosis and treatment. We
believe that native nephrectomy concurrent with transplantation can be
successfully performed when indicated in selected patients at experienced
centers.
PMID- 24356643
TI - Caries prevalence, oral hygiene, and oral health habits of Kuwaiti infants and
toddlers.
AB - OBJECTIVE: The purpose of this study was to describe the oral health, oral
hygiene, and oral health habits of Kuwaiti infants and toddlers. SUBJECTS AND
METHODS: This cross-sectional study of a convenience sample included 336 infants
and toddlers (156 females and 180 males). The teeth of the infants and toddlers
were examined using a mirror and a light source. Oral hygiene was recorded, and
then all teeth were cleaned with gauze and examined for caries. Parents were
interviewed regarding their children's feeding habits, brushing or tooth
cleaning, and night feeding. The evaluation criteria for caries were sound teeth,
noncavitated lesions, cavitated lesions, filled teeth, and missing teeth.
RESULTS: The mean age was 11.1 +/- 2.4 months (range 2-23). Of the 336 subjects,
247 (73%) had good oral hygiene, 64 (19%) had parents who brushed or cleaned
their infants' and toddlers' teeth; 288 (86%) were bottle-fed, and 290 (86%) were
also night fed. The mean number of teeth upon examination was 4.6 +/- 2.7 (range
2-8). Three percent of the infants and toddlers had caries. Cavitated lesions
were present in 6 patients (1.8%), while 4 (1.2%) had noncavitated lesions. The
mean d1d2t (caries teeth: noncavitated lesions and cavitated lesions) was 0.03 +/
0.3, and the mean d1d2s (carious surfaces) was 0.07 +/- 0.5. CONCLUSION: The
caries prevalence and severity was low in infants and toddlers. However, poor
oral health practices and habits as well as unhealthy feeding practices that
could affect the future caries prevalence were noted.
PMID- 24356644
TI - Organic matrix effects on the formation of light-absorbing compounds from alpha
dicarbonyls in aqueous salt solution.
AB - Aqueous-phase reactions of organic compounds are of general importance in
environmental systems. Reactions of alpha-dicarbonyl compounds in the aqueous
phase of atmospheric aerosols can impact their climate-relevant physical
properties including hygroscopicity and absorption of light. Less-reactive water
soluble organic compounds may contribute an organic matrix component to the
aqueous environment, potentially impacting the reaction kinetics. In this work we
demonstrate the effects of organic matrices on the self-reactions of glyoxal
(Gly) and methylglyoxal (mGly) in aqueous solutions containing ammonium sulfate.
At an organic-to-sulfate mass ratio of 2 : 1, carbohydrate-like matrices
resembling oxidized organic aerosol material reduce the rate of formation of
light-absorbing products by up to an order of magnitude. The greatest decreases
in the reaction rates were observed for organic matrices with smaller, more
linear molecular structures. Initial UV-Vis spectra, product studies, relative
rate data, acidity changes, and viscosity measurements suggest that shifts in
carbonyl equilibria, due in part to (hemi)acetal formation with the matrix,
reduce the rate of formation of light-absorbing imidazole and oligomer species.
PMID- 24356645
TI - Lamivudine treatment failure risks in chronic hepatitis B patients with low viral
load.
AB - AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the
long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In
this multicenter study, 548 antiviral naive noncirrhotic adult patients with LVL
(for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg-patients HBV DNA <10 7
copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients
with high viral load (HVL) were included. Primary outcome was switching to or
adding on another antiviral drug as a consequence of primary nonresponse, partial
response, viral breakthrough or adverse events. Secondary outcomes included LTF
rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS:
Among 594 patients, 294 had to change lamivudine at the follow-up. Primary
nonresponse, partial response, viral breakthrough or adverse events frequencies
were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and
84.2% in patients with LVL and HVL, respectively. Among patients with LVL,
patients with <100,000 copies/ml and >= 100,000 copies/ ml had 54.8 and 67.3% LTF
rates at the end of the 5th year, respectively. Logistic regression analysis of
risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response
at 6 months and duration of follow-up were independent predictors for LTF (p
values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION:
Similar to patients with HVL, first-line lamivudine therapy is not efficient for
long-term use in patients with LVL. LTF risk is so high even in the absence of
worse predictive factors.
PMID- 24356646
TI - Sequence, structure, and stacking: specifics of tRNA anchoring to the T box
riboswitch.
AB - The term riboswitch usually refers to small molecule sensing regulatory modules
in the 5' untranslated regions of a mRNA. They are typically comprised of
separate ligand binding and regulatory domains. The T box riboswitch is unique
from other identified riboswitches because its effector is an essential
macromolecule, tRNA. It senses the aminoacylation state of tRNA to regulate genes
involved in a variety of functions relating to amino acid metabolism and tRNA
aminoacylation. T box riboswitches performs an intuitively simple process using a
complex structured RNA element and, until recently, the underlying mechanisms
were poorly understood. Only two sequence-specific contacts had been previously
identified: (1) between the specifier sequence (codon) and the tRNA anticodon and
(2) between an anti-terminator stem loop and the tRNA acceptor arm CCA tail. tRNA
aminoacylation blocks the latter interaction and therefore serves as the switch
between termination and anti-termination. Outside of these two contacts, the
structure and functions of T box riboswitches have come to light in some recent
studies. We recently described the X-ray crystal structure of the highly
conserved T box riboswitch distal Stem I region and demonstrated that this region
interacts with the tRNA elbow to anchor it to the riboswitch. Independently,
Lehmann et al. used sequence homology search to arrive at a similar model for
Stem I-tRNA interactions. The model was further supported by two recent
structures of the Stem I-tRNA complex, determined independently by our group and
by Zhang and Ferre-D'Amare. This article highlights some of these contributions
to synthesize an updated model for tRNA recognition by the T box riboswitch.
PMID- 24356647
TI - Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with
visible or near-infrared fluorescent dyes for imaging pancreatic cancer in
orthotopic nude mouse models.
AB - The aim of this study was to evaluate a set of visible and near-infrared dyes
conjugated to a tumor-specific chimeric antibody for high-resolution tumor
imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer
was orthotopically implanted into pancreata of nude mice. Mice received a single
intravenous injection of a chimeric anti-carcinoembryonic antigen antibody
conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or
DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa
Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755).
After 24 h, the Olympus OV100 small-animal imaging system was used for
noninvasive and intravital fluorescence imaging of mice. Dyes were compared with
respect to depth of imaging, resolution, tumor-to-background ratio (TBR),
photobleaching, and hemoglobin quenching. The longer wavelength dyes had
increased depth of penetration and ability to detect the smallest tumor deposits
and provided the highest TBRs, resistance to hemoglobin quenching, and
specificity. The shorter wavelength dyes were more photostable. This study showed
unique advantages of each dye for specific cancer imaging in a clinically
relevant orthotopic model.
PMID- 24356648
TI - Enucleation and limited pancreatic resection provide long-term cure for
insulinoma in multiple endocrine neoplasia type 1.
AB - AIM: To assess the characteristics and long-term outcome after surgery in
patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma.
METHODS: Retrospective analysis of prospectively collected data of MEN1 patients
with organic hyperinsulinism at a tertiary referral center. RESULTS: Thirteen
(17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at
diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first
manifestation of the syndrome. All patients had at least one pancreatic
neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic
ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had
one dominant tumor with coexisting multiple small pNENs, and 2 patients had
multiple lesions without dominance. Eight patients had limited resections (1
segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1
patient a partial duodenopancreatectomy. There was no postoperative mortality.
Six patients experienced complications, including pancreatic fistula in 5
patients. Pathological examination revealed median three (range 1-14) macro-pNENs
sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were
detected in the 13 patients. After median follow-up of 156 months, only 1 patient
developed recurrent hyperinsulinism after initial enucleation. Twelve patients
developed new pNENs in the pancreatic remnant and 4 patients underwent
reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5
patients with an initial extended pancreatic resection developed insulin
dependent diabetes mellitus. CONCLUSION: Enucleation and limited resection
provide long-term cure for MEN1 insulinoma in patients with solitary or dominant
tumors. Subtotal distal pancreatectomy should thus be preserved for patients with
multiple pNENs without dominance given the risk of exocrine and endocrine
pancreas insufficiency in the mostly young patients.
PMID- 24356650
TI - Creativity and innovation in medical education: it's time to let the trees grow
freely.
PMID- 24356651
TI - Neurophobia in medical students and junior doctors--blame the GIK.
AB - INTRODUCTION: We aimed to create a definition of neurophobia, and determine its
prevalence and educational risk factors amongst medical students and junior
doctors in Singapore. MATERIALS AND METHODS: We surveyed medical students and
junior doctors in a general hospital using electronic and paper questionnaires.
We asked about knowledge, interest, perceived difficulty in neurology, and
confidence in managing neurology patients compared to 7 other internal medicine
specialties; quality and quantity of undergraduate and postgraduate neuroscience
teaching, clinical neurology exposure, and postgraduate qualifications.
Neurophobia was defined as <=4 composite score of difficulty and confidence with
neurology. RESULTS: One hundred and fifty-eight medical students (63.5%) and 131
junior doctors (73.2%) responded to the questionnaire. Neurophobia prevalence was
47.5% in medical students, highest amongst all medical subspecialties, and 36.6%
in junior doctors. Multivariate analysis revealed that for medical students,
female gender (OR 3.0, 95% CI, 1.3 to 6.7), low interest (OR 2.5, 95% CI, 1.0 to
6.2), low knowledge (OR 10.1, 95% CI, 4.5 to 22.8), and lack of clinical teaching
by a neurologist (OR 2.8, 95% CI, 1.2 to 6.6) independently increased the risk of
neurophobia. For doctors, low interest (OR 3.0, 95% CI, 1.3 to 7.0) and low
knowledge (OR 2.7, 95% CI, 1.2 to 6.2) independently increased the risk of
neurophobia, and female gender was of borderline significance (OR 2.0, 95% CI,
0.9 to 4.6). CONCLUSION: Neurophobia is highly prevalent amongst Singapore
medical students and junior doctors. Low interest and knowledge are independent
risk factors shared by both groups; female gender may also be a shared risk
factor. The mnemonic GIK (Gender, Interest, Knowledge) identifies the risk
factors to mitigate when planning teaching strategies to reduce neurophobia.
PMID- 24356649
TI - Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in
tumorigenesis.
AB - The tumour suppressor p53 is frequently mutated in tumours. Mutant p53 (Mutp53)
proteins often gain new activities in promoting tumorigenesis, defined as gain-of
function (GOF). Mutp53 can accumulate to high levels in tumours, which promotes
mutp53 GOF in tumorigenesis. The mechanism of mutp53 accumulation is poorly
understood. Here we find that MDM2 isoforms promote mutp53 accumulation in
tumours. MDM2 isoform B (MDM2-B), the MDM2 isoform most frequently over-expressed
in human tumours, interacts with full-length MDM2 to inhibit MDM2-mediated mutp53
degradation, promoting mutp53 accumulation and GOF in tumorigenesis. Furthermore,
MDM2-B overexpression correlates with mutp53 accumulation in human tumours. In
mutp53 knock-in mice, a MDM2 isoform similar to human MDM2-B is overexpressed in
the majority of tumours, which promotes mutp53 accumulation and tumorigenesis.
Thus, overexpression of MDM2 isoforms promotes mutp53 accumulation in tumours,
contributing to mutp53 GOF in tumorigenesis. This may be an important mechanism
by which MDM2 isoforms promote tumorigenesis.
PMID- 24356652
TI - Attitudes and Practices on the Consent Process and Decision-making for
Intravenous Stroke Thrombolysis: Physicians' Perspective.
AB - INTRODUCTION: Earlier treatment with intravenous stroke thrombolysis improves
outcomes and lowers risk of bleeding complications. The decision-making and
consent process is one of the rate-limiting steps in the duration between
hospital arrival and treatment initiation. We aim to describe the attitudes and
practices of neurologists in Singapore on the consent and decision-making
processes for stroke thrombolysis. MATERIALS AND METHODS: A survey of
neurologists and neurologists-in-training in 2 large tertiary public hospitals in
Singapore was conducted. RESULTS: Among 46 respondents, 94% of them considered
stroke thrombolysis an emergency treatment and 67% of them indicated there is a
need for written informed consent. The majority (87%) knew that from a legal
perspective, the doctor should be the decision-maker in an emergency treatment
for a mentally incapacitated patient. However, 63% of respondents reported that
it is the next-of-kin who usually makes the decision in actual practice. If
confronted with a mentally incapacitated stroke patient, 57% of them were willing
to be the proxy decision-maker and 13% of them were not. In 3 commonly
encountered vignettes when a mentally incapacitated patient was being considered
for stroke thrombolysis, there was no clear consensus on the respondents'
practices. CONCLUSION: The next-of-kin is usually the decision-maker for stroke
thrombolysis in practice for a mentally incapacitated patient despite most
doctors considering thrombolysis an emergency treatment. This, together with the
lack of consensus and variance in decision-making and consent practice amongst
neurologists for stroke thrombolysis, demonstrates the need to develop best
practice guidelines to standardise healthcare practices for greater consistency
in health service delivery.
PMID- 24356653
TI - An Outbreak of Community Associated Methicillin Resistant Staphylococcus aureus
Subtype USA300 at an International School in Singapore.
AB - Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
subtype USA300 remains relatively well confined within North American shores.
Between August and November 2010, a large international school in Singapore
recorded 27 skin and soft tissue infections, 8 of which were confirmed USA 300.
This study reports the outbreak investigation and the interventions instituted.
PMID- 24356654
TI - Integrated care pathway for hip fractures in a subacute rehabilitation setting.
AB - INTRODUCTION: The effectiveness of integrated care pathways for hip fractures in
subacute rehabilitation settings is not known. The study objective was to assess
if a hip fracture integrated care pathway at a subacute rehabilitation facility
would result in better functional outcomes, shorter length of stay and fewer
institutionalisations. MATERIALS AND METHODS: A randomised controlled trial on an
integrated care pathway for hip fracture patients in a subacute rehabilitation
setting. Modified Barthel Index, ambulatory status, SF-12, length of stay,
discharge destination, hospital readmission and mortality were measured. Followup
assessments were up to 1 year post-hip fracture. RESULTS: There were no
significant differences in Montebello Rehabilitation Factor Scores and
proportions achieving premorbid ambulatory status at discharge, 6 months and 12
months respectively. There was a significant reduction in the median length of
stay between the control group at 48.0 days and the intervention group at 35.0
days (P = 0.009). The proportion of readmissions to acute hospitals was similar
in both groups up to 1 year. There were no significant differences for nursing
home stay up to 1 year post-discharge and mortality at 1 year. CONCLUSION: Our
study supports the use of integrated care pathways in subacute rehabilitation
settings to reduce length of stay whilst achieving the same functional gains.
PMID- 24356655
TI - C-arm Cone Beam Computed Tomography: A New Tool in the Interventional Suite.
AB - INTRODUCTION: C-arm Cone Beam CT (CBCT) is a technology that is being integrated
into many of the newer angiography systems in the interventional suite. Due to
its ability to provide cross sectional imaging, it has opened a myriad of
opportunities for creating new clinical applications. We review the technical
aspects, current reported clinical applications and potential benefits of this
technology. MATERIALS AND METHODS: Searches were made via PubMed using the string
"CBCT", "Cone Beam CT", "Cone Beam Computed Tomography" and "C-arm Cone Beam
Computed Tomography". All relevant articles in the results were reviewed.
RESULTS: CBCT clinical applications have been reported in both vascular and non
vascular interventions. They encompass many aspects of a procedure including
preprocedural planning, intraprocedural guidance and postprocedural assessment.
As a result, they have allowed the interventionalist to be safer and more
accurate in performing image guided procedures. There are however several
technical limitations. The quality of images produced is not comparable to
conventional computed tomography (CT). Radiation doses are also difficult to
quantify when compared to CT and fluoroscopy. CONCLUSION: CBCT technology in the
interventional suite has contributed significant benefits to the patient despite
its current limitations. It is a tool that will evolve and potentially become an
integral part of imaging guidance for intervention.
PMID- 24356656
TI - Consensus recommendations for preventing and managing bleeding complications
associated with novel oral anticoagulants in singapore.
AB - INTRODUCTION: Novel oral anticoagulants (NOACs) have at least equivalent efficacy
compared to standard anticoagulants with similar bleeding risk. Optimal
management strategies for bleeding complications associated with NOACs are
currently unestablished. MATERIALS AND METHODS: A working group comprising
haematologists and vascular medicine specialists representing the major
institutions in Singapore was convened to produce this consensus recommendation.
A Medline and EMBASE search was conducted for articles related to the 3 available
NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management.
Additional information was obtained from the product monographs and bibliographic
search of articles identified. RESULTS: The NOACs still has substantial
interactions with a number of drugs for which concomitant administration should
best be avoided. As they are renally excreted, albeit to different degrees, NOACs
should not be prescribed to patients with creatinine clearance of <30 mLs/min.
Meticulous consideration of risk versus benefits should be exercised before
starting a patient on a NOAC. In patients presenting with bleeding, risk
stratification of the severity of bleeding as well as identification of the
source of bleeding should be performed. In life-threatening bleeds, recombinant
activated factor VIIa and prothrombin complex may be considered although their
effectiveness is currently unsupported by firm clinical evidence. The NOACs have
varying effect on the prothrombin time and activated partial thromboplastin time
which has to be interpreted with caution. Routine monitoring of drug level is not
usually required. CONCLUSION: NOACs are an important advancement in
antithrombotic management and careful patient selection and monitoring will
permit optimisation of their potential and limit bleeding events.
PMID- 24356657
TI - Observer-Reporter-Interpreter-Manager-Educator (ORIME) Framework to Guide
Formative Assessment of Medical Students.
AB - The Observer-Reporter-Interpreter-Manager-Educator (ORIME) is adapted from RIME,
an intuitive, self-explanatory and "synthetic" framework that assesses
formatively, a student's ability to synthesise knowledge, skills and attitude
during a clinical encounter with a patient. The "O" refers to a student's ability
to pay attention and perceive with open-mindedness, people and events around him
or her. The framework is suitable for definition of interim outcomes in a 5-year
undergraduate programme. To align students' and clinical teachers' expectations
further, selection of case complexity that is commensurate with student's
seniority and competence should be guided and an adapted version of the Minnesota
Complexity Assessment Tool is proposed.
PMID- 24356658
TI - Molecular biomarkers at the interface of basic and clinical dengue research.
PMID- 24356659
TI - Surgeons Take on End-of-Life Care.
PMID- 24356660
TI - Ramadan and eye drops: attitudes and practices of Malay Muslims in Singapore.
PMID- 24356661
TI - Outcome of extracorporeal membrane oxygenation for neonatal refractory
respiratory failure.
PMID- 24356662
TI - Painful Nodular Lesions over the Hands.
PMID- 24356663
TI - An unusual cause of bronchiectasis and asthma.
PMID- 24356664
TI - Conflict of Interest in Research--The Clinician Scientist's Perspective.
AB - Conflict of interest (COI) in research represents situations that pose risks of
undue influence on scientific objectivity and judgment because of secondary
interests. This is complex but is inherent to biomedical research. The role of a
clinician scientist can be conflicted when scientific objectivity is perceived to
compete with scientific success (publications, grants), partiality to patients
(clinical trials), obligations to colleagues (allowing poor scholarship to pass),
research sponsors (industry), and financial gains (patents, royalties). While
there are many ways which COIs can occur in research, COI mitigations remain
reliable. Collaborations between investigators and industry are valuable to the
development of novel therapies and undue discouragement of these relationships
may inadvertently harm the advancement of healthcare. As a result, proper
management of COI is fundamental and crucial to the maintenance of long-term,
mutually beneficial relationships between industry and academia. The nature of
COI in research and methods of mitigation are discussed from the perspective of a
clinician scientist.
PMID- 24356665
TI - The impact of shell host (NaYF4/CaF2) and shell deposition methods on the up
conversion enhancement in Tb3+, Yb3+ codoped colloidal alpha-NaYF4 core-shell
nanoparticles.
AB - Lanthanide doped, up-converting nanoparticles have found considerable interest as
luminescent probes in the field of bio-detection. Although the nanoparticles
(NPs) have already been successfully applied for fluorescent bio-imaging and bio
assays, the efficiency of the up-conversion process seems to be the bottle-neck
in rigorous applications. In this work, we have shown enhancement of the up
conversion in colloidal alpha-NaYF4:Yb(3+), Tb(3+) doped nanocrystals owing to
passivation of their surface. We have studied quantitatively the influence of the
shell type (NaYF4 and CaF2), its thickness, as well as the shell deposition
method (i.e. single thick shell vs. multi-layer shell) on the luminescent
properties of the nanoparticles. The results showed that up to 40-fold up
conversion intensity enhancement may be obtained for the core-shell nanoparticles
in comparison with the bare core nanoparticles, irrespective of the shell type
and deposition method. Moreover, the suitability of the NaYF4:Yb(3+), Tb(3+) core
shell NPs for multi-color emission and spectral multiplexing has been presented.
PMID- 24356666
TI - Quantifying the relationship between financial news and the stock market.
AB - The complex behavior of financial markets emerges from decisions made by many
traders. Here, we exploit a large corpus of daily print issues of the Financial
Times from 2(nd) January 2007 until 31(st) December 2012 to quantify the
relationship between decisions taken in financial markets and developments in
financial news. We find a positive correlation between the daily number of
mentions of a company in the Financial Times and the daily transaction volume of
a company's stock both on the day before the news is released, and on the same
day as the news is released. Our results provide quantitative support for the
suggestion that movements in financial markets and movements in financial news
are intrinsically interlinked.
PMID- 24356667
TI - Pharmacological approach to diabetic macular edema.
AB - Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a
remarkable impact on public health, and on the quality of life of diabetic
patients. Even though laser photocoagulation has been the standard of care for
decades, a substantial group of patients are unresponsive and fail to improve
after laser treatment. Recently, new pharmacological approaches based on the use
of intravitreal drugs, such as corticosteroids and anti-vascular endothelial
growth factor, have revolutionized the treatment of DME. The use of intravitreal
drugs is supported by the improvement in visual acuity reported by several
clinical trials and can limit the potentially destructive effects of the laser
treatment. Encouraging results also emerged from studies evaluating the use of a
combination therapy, or the association of intravitreal drugs and laser
treatment. This review aims at providing a brief synopsis of the main
investigations regarding the current pharmacological approach to DME.
PMID- 24356668
TI - Optimization of growth and ordering of Ag nanoparticle arrays on ripple patterned
alumina surfaces for strong plasmonic coupling.
AB - Low-energy ion beam sputtering of alumina thin films followed by growth of
metallic nanoparticles by glancing angle deposition is optimized in order to
produce arrays of silver nanoparticle chains with a strong plasmonic dichroism. A
systematic study is undertaken in order to establish the influence of the angle
of silver deposition and the ordering of the pre-patterned rippled surface on the
morphology and organization of the nanoparticles, and on their associated optical
properties. High ion fluence for ripple formation and low glancing angle for
metal deposition favor the formation of aligned and elongated particles with sub
nanometer gaps. Numerical simulations show that these nanoparticle arrays
generate high electric field enhancements for an excitation parallel to the
particle chains, and therefore can be used for surface enhanced spectroscopies.
PMID- 24356669
TI - Embryo reduction in dichorionic triplets to dichorionic twins by intrafetal
laser.
AB - OBJECTIVE: To describe a new technique for embryo reduction (ER) in dichorionic
triplet (DCT) pregnancies. METHODS: In 22 DCT pregnancies, ER to dichorionic
twins was carried out at 11.3-13.9 weeks' gestation by ultrasound-guided laser
ablation of the pelvic vessels of one of the monochorionic twins. RESULTS:
Intrafetal laser was successfully carried out in all cases, but ultrasound
examination within 2 weeks of the procedure demonstrated that the co-twin had
died in 11 cases and was alive in the other 11. In the dichorionic group there
was one miscarriage at 23 weeks due to cervical incompetence and in the other 10
cases there were two live births at a median gestational age of 35.0 (range 32.2
37.1) weeks. In the 11 cases where both monochorionic fetuses died the separate
triplet was live born at a median gestation of 38.0 (range 32.2-40.5) weeks.
CONCLUSIONS: In the management of DCT pregnancies, ER to dichorionic twins by
intrafetal laser is an additional option to the traditional ones of expectant
management, ER by intrafetal injection of potassium chloride (KCl) to
monochorionic twins or ER by KCl to singleton.
PMID- 24356670
TI - In situ chemical probing of the electrode-electrolyte interface by ToF-SIMS.
AB - A portable vacuum interface allowing direct probing of the electrode-electrolyte
interface was developed. A classical electrochemical system consisting of a gold
working electrode, platinum counter electrode, platinum reference electrode, and
potassium iodide electrolyte was used to demonstrate real-time observation of the
gold iodide adlayer on the electrode and chemical species as a result of redox
reactions using cyclic voltammetry (CV) and time-of-flight secondary ion mass
spectrometry (ToF-SIMS, a vacuum-based surface technique) simultaneously. This
microfluidic electrochemical probe provides a new way to investigate the surface
region with adsorbed molecules and the region of the diffused layer with chemical
speciation in liquids in situ by surface sensitive techniques.
PMID- 24356672
TI - Chronic NSAID use and long-term decline of renal function in a prospective
rheumatoid arthritis cohort study.
AB - OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause kidney
damage. This study assessed the impact of prolonged NSAID exposure on renal
function in a large rheumatoid arthritis (RA) patient cohort. METHODS: Renal
function was prospectively followed between 1996 and 2007 in 4101 RA patients
with multilevel mixed models for longitudinal data over a mean period of 3.2
years. Among the 2739 'NSAID users' were 1290 patients treated with
cyclooxygenase type 2 selective NSAIDs, while 1362 subjects were 'NSAID naive'.
Primary outcome was the estimated glomerular filtration rate according to the
Cockroft-Gault formula (eGFRCG), and secondary the Modification of Diet in Renal
Disease and Chronic Kidney Disease Epidemiology Collaboration formula equations
and serum creatinine concentrations. In sensitivity analyses, NSAID dosing
effects were compared for patients with NSAID registration in <=/>50%, <=/>80% or
<=/>90% of assessments. FINDINGS: In patients with baseline eGFRCG >30 mL/min,
eGFRCG evolved without significant differences over time between 'NSAID users'
(mean change in eGFRCG -0.87 mL/min/year, 95% CI -1.15 to -0.59) and 'NSAID
naive' (-0.67 mL/min/year, 95% CI -1.26 to -0.09, p=0.63). In a multivariate Cox
regression analysis adjusted for significant confounders age, sex, body mass
index, arterial hypertension, heart disease and for other insignificant factors,
NSAIDs were an independent predictor for accelerated renal function decline only
in patients with advanced baseline renal impairment (eGFRCG <30 mL/min). Analyses
with secondary outcomes and sensitivity analyses confirmed these results.
CONCLUSIONS: NSAIDs had no negative impact on renal function estimates but in
patients with advanced renal impairment.
PMID- 24356674
TI - The fraud and retraction epidemic.
PMID- 24356673
TI - High-resolution MRI evaluation of neonatal brachial plexus palsy: A promising
alternative to traditional CT myelography.
AB - BACKGROUND AND PURPOSE: Despite recent improvements in perinatal care, the
incidence of neonatal brachial plexus palsy remains relatively common. CT
myelography is currently considered to be the optimal imaging technique for
evaluating nerve root integrity. Recent improvements in MR imaging techniques
have made it an attractive alternative to evaluate nerve root avulsions
(preganglionic injuries). We aim to demonstrate utility of MR imaging in the
evaluation of normal and avulsed spinal nerve roots. MATERIALS AND METHODS: All
study patients with clinically diagnosed neonatal brachial plexus palsy underwent
MR imaging by use of a high-resolution, heavily T2-weighted (driven equilibrium)
sequence. MR imaging findings were reviewed for presence of nerve root avulsion
from C5-T1 and for presence of pseudomeningocele. The intraoperative findings
were reviewed and compared with the preoperative MR imaging findings. RESULTS:
Thirteen patients (9 male, 4 female) underwent MR imaging; 6 patients underwent
nerve reconstruction surgery, during which a total of 19 nerve roots were
evaluated. Eight avulsions were noted at surgery and in the remainder, the nerve
injury was more distal (rupture/postganglionic injury). Six of the 8 nerve root
avulsions identified at surgery were at C5-6 level, whereas 1 nerve root avulsion
was identified at C7 and C8 levels, respectively. The overall sensitivity and
specificity of MR imaging for nerve root avulsions was 75% and 82%, respectively.
CONCLUSIONS: Our preliminary results demonstrate that high-resolution MR imaging
offers an excellent alternative to CT myelography for the evaluation of neonatal
brachial plexus palsy with similar sensitivity compared with CT myelography.
PMID- 24356675
TI - Treatment of cavernous sinus aneurysms with flow diversion: results in 44
patients.
AB - BACKGROUND AND PURPOSE: Aneurysms of the cavernous segment of the ICA are
difficult to treat with standard endovascular techniques, and ICA sacrifice
achieves a high rate of occlusion but carries an elevated level of surgical
complications and risk of de novo aneurysm formation. We report rates of
occlusion and treatment-related data in 44 patients with cavernous sinus
aneurysms treated with flow diversion. MATERIALS AND METHODS: Patients with
cavernous segment aneurysms treated with flow diversion were selected from a
prospectively maintained data base of patients from 2009 to the present.
Demographic information, treatment indications, number/type of flow diverters
placed, outcome, complications (technical or clinical), and clinical/imaging
follow-up data were analyzed. RESULTS: We identified 44 patients (37 females, 7
males) who had a flow diverter placed for treatment of a cavernous ICA aneurysm
(mean age, 57.2; mean aneurysm size, 20.9 mm). The mean number of devices placed
per patient was 2.2. At final angiographic follow-up (mean, 10.9 months), 71% had
complete occlusion, and of those with incomplete occlusion, 40% had minimal
remnants (<3 mm). In symptomatic patients, complete resolution or significant
improvement in symptoms was noted in 90% at follow-up. Technical complications
(which included, among others, vessel perforation in 4 patients, groin hematoma
in 2, and asymptomatic carotid occlusion in 1) occurred in approximately 36% of
patients but did not result in any clinical sequelae immediately or at follow-up.
CONCLUSIONS: Our series of flow-diversion treatments achieved markedly greater
rates of complete occlusion than coiling, with a safety profile that compares
favorably with that of carotid sacrifice.
PMID- 24356676
TI - Coil occlusion of wide-neck bifurcation aneurysms assisted by a novel intra- to
extra-aneurysmatic neck-bridging device (pCONus): initial experience.
AB - BACKGROUND AND PURPOSE: The pCONus is a new stentlike self-expanding nitinol
implant with 4 distal petals, which is fully retrievable and electrolytically
detachable. The distal end is implanted inside the aneurysm at the neck. The
shaft is anchored in the parent vessel. In selected wide-neck bifurcation
aneurysms, the pCONus was used to assist coiling. The device was evaluated for
its safety and efficacy. MATERIAL AND METHODS: Twenty-eight patients with 28 wide
neck aneurysms (9 recently ruptured) were treated with pCONus-assisted coiling at
the discretion of the operator. Other treatment options were considered but were
discarded due to anticipated difficulties. Technical issues, immediate
posttreatment angiographic findings, clinical outcome, and follow-up imaging were
assessed. RESULTS: There were 11 MCA, 7 anterior communicating artery, 1
posterior cerebral artery, 1 A2, and 8 basilar artery aneurysms. Insertion and
deployment of the pCONus and subsequent coiling were possible in all cases. There
were no clinically evident complications associated with the use of the device.
Initial anatomic outcome showed 8 complete occlusions, 9 neck remnants, and 11
incomplete occlusions. Neurologic status remained unchanged at follow-up.
Angiographic controls were obtained in 22 patients (mean, 7.5 months). Of these,
13 had complete occlusion, 9 showed improvement, and 7 were unchanged. Four died
from SAH sequelae or other diseases, and 2 have not yet undergone follow-up. No
intimal hyperplasia was observed. CONCLUSIONS: The pCONus facilitates coil
occlusion of unruptured and ruptured wide-neck bifurcation aneurysms. The device
can be deployed safely. Coil retention is sufficient to protect the efferent
vessels. So far, no intimal hyperplasia in the shaft has been observed.
PMID- 24356677
TI - Changes in the thalamus in atypical parkinsonism detected using shape analysis
and diffusion tensor imaging.
AB - BACKGROUND AND PURPOSE: The thalamus is interconnected with the nigrostriatal
system and cerebral cortex and has a major role in cognitive function and
sensorimotor integration. The purpose of this study was to determine how regional
involvement of the thalamus differs among Parkinson disease, progressive
supranuclear palsy, and corticobasal syndrome. MATERIALS AND METHODS: Nine
patients with Parkinson disease, 5 with progressive supranuclear palsy, and 6
with corticobasal syndrome underwent 3T MR imaging along with 12 matched,
asymptomatic volunteers by using a protocol that included volumetric T1 and
diffusion tensor imaging. Acquired data were automatically processed to delineate
the margins of the motor and nonmotor thalamic nuclear groups, and measurements
of ADC were calculated from the DTI data within these regions. Thalamic volume,
shape, and ADC were compared across groups. RESULTS: Thalamic volume was smaller
in the progressive supranuclear palsy and corticobasal syndrome groups compared
with the Parkinson disease and control groups. Shape analysis revealed that this
was mainly due to the diminished size of the lateral thalamus. Overall, ADC
measurements were higher in the progressive supranuclear palsy group compared
with both the Parkinson disease and control groups, and anatomic subgroup
analysis demonstrated that these changes were greater within the motor regions of
the thalamus in progressive supranuclear palsy and corticobasal degeneration.
CONCLUSIONS: Reduced size and increased ADC disproportionately involve the
lateral thalamus in progressive supranuclear palsy and corticobasal syndrome,
consistent with selective neurodegeneration and atrophy in this region. Because
these findings were not observed in Parkinson disease, they may be more specific
markers of tau-related neurodegeneration.
PMID- 24356678
TI - Application of the A.S.P.E.N. clinical guideline for nutrition support of
hospitalized adult patients with obesity: a case study of home parenteral
nutrition.
AB - An A.S.P.E.N. clinical guideline addressing the nutrition support of hospitalized
adult patients with obesity was recently published in the Journal of Parenteral
and Enteral Nutrition. Among the patient presentations for which this guideline
might be used is those who have a gastrointestinal complication after bariatric
surgery. A case study is discussed of a 43-year-old woman with a long history of
severe obesity who had a bowel obstruction approximately 2 weeks after her
laparoscopic sleeve gastrectomy surgery. The patient's treatment plan for bowel
rest and home parenteral nutrition was based on the A.S.P.E.N. clinical guideline
for patients with obesity. She tolerated the course well and resumed the expected
diet advancement and weight loss patterns expected of her weight-loss surgery.
PMID- 24356680
TI - Effects and therapeutic potentials of kisspeptin analogs: regulation of the
hypothalamic-pituitary-gonadal axis.
AB - The hypothalamic peptide kisspeptin (metastin), the endogenous ligand of the G
protein-coupled receptor KISS1R, plays a critical role in controlling GnRH
release from hypothalamic GnRH neurons and thereby regulates hypothalamic
pituitary-gonadal functions. Although the therapeutic potential of kisspeptin is
attractive, its susceptibility to proteolytic degradation limits its utility. To
overcome this, KISS1R agonists or antagonists as peptide analogs or small
molecules have been investigated. Kisspeptin analogs have been most extensively
studied by reducing the length of the peptide from the original 54 amino acids to
10 amino acids or less and by substituting key amino acid residues. Also, 2
investigational kisspeptin agonist analogs have been evaluated in clinical
studies in men; in agreement with animal studies, abrupt elevations in
gonadotropin and testosterone levels were observed as an acute effect, followed
by rapid reductions in these hormones as a chronic effect. Some studies of small
molecule KISS1R antagonists have also been published. In this review, we present
a brief overview on kisspeptin/KISS1R physiology in reproductive functions and
summarize the available knowledge of both agonists and antagonists. We also focus
on the kisspeptin agonist analogs by summarizing key pharmacological findings
from both clinical and preclinical studies, and discuss their potential
therapeutic utility.
PMID- 24356679
TI - Changes in the clinical characteristics, treatment options, and therapy outcomes
in patients with phyllodes tumor of the breast during 55 years of experience.
AB - BACKGROUND: Data from the literature suggests that the clinical picture of
phyllodes tumor (PT) of the breast, as well as treatment options and perhaps
therapy outcomes, have significantly changed. The aim of this work was to review
these changes by analysis of consecutive patients with PT over a 55-year period
at a single institution. MATERIAL AND METHODS: From 1952 to 2007, 280 women with
PT were treated surgically at the Maria Sklodowska-Curie Memorial Institute of
Oncology, Cancer Center in Cracow. Age, size of breast tumor, microscopic type,
extent of surgery, and therapy outcomes were compared between 2 groups: 190
patients treated from 1952 to 1991 vs 90 patients treated from 1992 to 2007.
RESULTS: The results show that the 1992-2007 group compared to the 1952-1991
included more patients <50 years of age, with tumor <5 cm in diameter, undergoing
breast-conserving therapy, as well as no evidence of disease at 5-year survival
had increased and this change was statistically significant. In addition,
malignant PT cases had decreased in frequency. CONCLUSIONS: The results of this
study show that patients with PT are increasingly younger, the breast tumors at
diagnosis are smaller, malignant PT is becoming less frequent, and BCT is now the
treatment of choice. Most importantly, the general treatment outcomes are
significantly better.
PMID- 24356681
TI - Dielectric response of pentagonal defects in multilayer graphene nano-cones.
AB - The dielectric response of pentagonal defects in multilayer graphene nano-cones
has been studied by electron energy loss spectroscopy and ab initio simulations.
At the cone apex, a strong modification of the dielectric response is observed
below the energy of the pi plasmon resonance. This is attributed to pi -> pi*
interband transitions induced by topology-specific resonant pi bonding states as
well as pi*-sigma* hybridization. It is concluded that pentagonal defects
strongly affect the local electronic structure in such a way that multi-walled
graphene nano-cones should show great promise as field emitters.
PMID- 24356683
TI - Clinical trials and the pharmaceutical industry.
PMID- 24356684
TI - [Health and the good life: contributions by Amartya Sen's capability approach to
ethical reasoning in public health].
AB - The aim of this article is to analyze the contribution by Amartya Sen's
capability approach to ethical reasoning in public health. Based on critiques by
the capability approach towards utilitarianism, the article proposes a concept of
health based on four characteristics: a pluralistic notion of good life,
expansion of freedom as the ethical foundation for health actions, a concept of
person as agent, and recognition of the inner view of health based on positional
objectivity. The contribution by the capability approach to ethical reasoning in
public health can be summarized in four points: insufficiency of healthcare as a
criterion for individual advantage, health equity as a part of social justice,
the relevance of individual self-rated health, and the development of capability
as an ultimate goal of public policies in public health.
PMID- 24356685
TI - [Social representations of the body: a study of adolescents in the city of Rio de
Janeiro, Brazil].
AB - Body changes are central to adolescence as a stage of life. To approach conflicts
experienced by adolescents with body changes, this study aimed to identify social
representations of the body among adolescents in the last year of primary school
in private and municipal schools in Rio de Janeiro, Brazil. Participants were 13
to 18 years of age and studied in schools in neighborhoods with the highest and
lowest scores on the Social Development Index. Focus groups were used to produce
social representation of the body. Groups began by evoking five words that came
to mind when hearing the word "body". The EVOC program was used to treat evoked
words, complemented by thematic content analysis. Many teenagers spoke of
"beauty" as synonymous with "beautiful body" and described a model of beauty: a
muscular body for teenage boys and a slender and shapely body for teenage girls.
PMID- 24356686
TI - Intimate partner violence and unintended pregnancy: prevalence and associated
factors.
AB - This study investigated the association between unintended pregnancy and intimate
partner violence before pregnancy. A cross-sectional study was carried out with
1,054 women, aged 18 to 49, in Recife, Northeastern Brazil, from July 2005 to
March 2006. Non-conditional logistic regression analysis was performed with a
hierarchical strategy for entering variables into the model, according to the
conceptual framework defined. Unintended pregnancy was reported by 60.3% (636)
women. Intimate partner violence prior to the pregnancy was associated with
unintended pregnancy (OR adj = 1.57; 95%CI: 1.17-2.11), even when adjusted for
the women's sociodemographic characteristics, the partner's behaviour, and the
relationship dynamic. When the association was adjusted for the use of
contraception and the partner's refusal to use contraception, the association was
no longer significant, suggesting that the effect of partner violence on
unintended pregnancy may be mediated by these variables. The findings point to
the need of screening for intimate partner violence in reproductive health
services.
PMID- 24356687
TI - [A comprehensive study on suicide among older women in seven Brazilian cities].
AB - This article is based on a multicenter study in Brazil, analyzing 51 cases of
suicide in elderly individuals (40 men and 11 women) based on psychosocial
autopsies. A more in-depth study was conducted on the 11 cases in women. Data
interpretation was based on classical authors and the recent national and
international literature on the phenomenon. Women's motives for committing
suicide differed partially from those of men. Like men, women committed suicide
mainly by hanging themselves, and their suicide was frequently associated with
degenerative illnesses and comorbidities. The main differences were due to
cultural gender issues. The results agree largely with the literature and show
that in Brazil the main factors associated with suicide in women are: gender and
intra-family violence, suffering due to loss of significant others and the
traditional role of wife and mother, and depression. The study highlights the
importance of greater attention to the cumulative effect of problems with aging
in women, especially those related to gender specificities.
PMID- 24356688
TI - [Dietary patterns and associated factors among children one to six years of age
in a city in southern Brazil].
AB - This study aimed to describe dietary patterns and to investigate associations
with demographic and socioeconomic factors among children one to six years of age
in the city of Pelotas, Rio Grande do Sul State, Brazil. Pearson correlation was
used to group different foods. Dietary patterns were constructed using principal
components analysis (PCA). Associations were established with the Kruskal Wallis
test (alpha = 0.05). The study evaluated 667 children. Five dietary patterns were
identified: "vegetables", "traditional" (bread, butter/margarine, rice/pasta,
coffee, sugar), "sweets and sausages", "snacks" (dairy products, chocolate,
cookies, and juice), and "fruits". Children of mothers with more schooling and
higher income showed greater adherence to "vegetables" and "fruits". The
"traditional" pattern was more common in children of mothers with less education
and lower family income. The "vegetables" and "traditional" patterns showed
greater variance. Families' socioeconomic status played a key role in determining
children's dietary patterns.
PMID- 24356689
TI - [A comparative study of social representations of diabetes mellitus and diabetic
foot].
AB - The study aimed to investigate social representations of the terms "diabetes" and
"diabetic foot" in different populations. Participants were divided into groups:
diabetics (GD); non- diabetics (GN); and non-diabetic healthcare professionals
(GP). Personal data were collected, and subjects answered two questions that were
expected to evoke five words that came to mind when they thought of "diabetes"
and then "diabetic foot". The evoked material was analyzed with the software
Ensemble de Programmes Permettant l'Analyse des Evocations. A total of 161
subjects participated, including GD (n = 72) with a mean age of 56.12 +/- 5.49
years; GN (n = 38) with a mean age of 54.29 +/- 7.91 years; and GP (n = 51) with
34.95 +/- 7.52 years. The term "diabetes" evoked 297 words in GD, 172 in GN, and
235 words in GP. The term "diabetic foot" evoked 180 words in GD, 90 in GN, and
236 in GP. The groups proved to be anxious for more information, thus confirming
the need for awareness-raising and educational programs on diabetes, covering
comprehensive issues concerning the disease.
PMID- 24356690
TI - [Women's narratives on care received in a birthing center].
AB - Women's perception of childbirth care in a birthing center, the focus of this
study, should be considered to assess and improve quality of care. The study
method was narrative analysis. Inductive and interpretative analysis of
narratives by 17 women produced the following descriptive categories: distinct
experiences with care received upon arrival at the hospital; diversity of
experiences with patient's self-care and procedures performed by healthcare
staff; conflicting opinions on the husband or partner's presence during
childbirth; and degree of satisfaction with follow-up, interpersonal relations,
and orientation by the healthcare team. Childbirth care was evaluated positively
by mothers, and this result supports the current Brazilian public policy
recommending expansion of birthing centers.
PMID- 24356691
TI - Factors associated with low life life satisfaction in community-dwelling elderly:
FIBRA Study.
AB - The objectives were to identify factors associated with decreased life
satisfaction in community-dwelling elderly and describe such factors according to
gender and age bracket. The study interviewed 2,472 elderly individuals 65 years
or older without cognitive deficits suggestive of dementia, in probabilistic
samples from seven Brazilian cities. All measures were self-reported except for
functional performance, indicated by handgrip and gait speed. Women had more
chronic diseases, worse functional performance, and greater social involvement
when compared to men. The oldest participants showed worse functional performance
and less social involvement when compared to the youngest. Low satisfaction was
associated with three or more diseases, memory problems, low social involvement,
low handgrip strength, and urinary incontinence. The authors conclude that
health, functional performance, and social involvement interact with well-being,
so interventions targeting these areas can favor quality of life for the elderly.
PMID- 24356692
TI - Cost-effectiveness of prevention strategies for American tegumentary
leishmaniasis in Argentina.
AB - The aim of this study was to estimate the cost-effectiveness of reducing
tegumentary leishmaniasis transmission using insecticide-impregnated clothing and
curtains, and implementing training programs for early diagnosis. A societal
perspective was adopted, with outcomes assessed in terms of costs per disability
adjusted life years (DALY). Simulation was structured as a Markov model and costs
were expressed in American dollars (US$). The incremental cost-effectiveness
ratio of each strategy was calculated. One-way and multivariate sensitivity
analyses were performed. The incremental cost-effectiveness ratio for early
diagnosis strategy was estimated at US$ 156.46 per DALY averted, while that of
prevention of transmission with insecticide-impregnated curtains and clothing was
US$ 13,155.52 per DALY averted. Both strategies were more sensitive to the
natural incidence of leishmaniasis, to the effectiveness of mucocutaneous
leishmaniasis treatment and to the cost of each strategy. Prevention of vectorial
transmission and early diagnosis have proved to be cost-effective measures.
PMID- 24356693
TI - [Working conditions on public buses and common mental disorders among drivers and
fare collectors: Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil,
2012].
AB - Common mental disorders (CMD) contribute to overall burden of disease. The
current study aimed to describe the prevalence of CMD among a sample of bus
drivers and fare collectors in Greater Metropolitan Belo Horizonte, Minas Gerais
State, Brazil, and investigate whether traffic conditions and conditions inside
buses were associated with the outcome. This non-probabilistic sample of 1,607
workers was estimated from the size of the effective workforce (n = 17,470). Face
to-face interviews used a digital questionnaire with online data processing.
Overall prevalence of CMD was 23.6%. Bad traffic conditions lost statistical
significance in the multivariate analysis, while higher income and adverse
working conditions and inadequate safety remained associated with the outcome.
Harmful behavior and vulnerable health situations were associated with CMD. This
study of urban bus workers' health is a unique contribution that can provide
backing for public policies targeting metropolitan populations.
PMID- 24356694
TI - [Analysis of barriers to the use of thrombolytics in ischemic stroke in a private
hospital in Rio de Janeiro, Brazil].
AB - Ischemic stroke is a major cause of neurological sequelae and death. The correct
use of thrombolytic therapy faces several barriers. The objective was to discuss
barriers to thrombolytic therapy in a private hospital. This was a retrospective
cohort study of patients with symptoms of acute ischemic stroke entering the
emergency department of a private hospital in Rio de Janeiro, Brazil, from 2009
to 2011. 257 patients were admitted with suspected ischemic stroke. Among the 156
patients with confirmed diagnosis of ischemic stroke, 18 (11.5%) received
thrombolytic therapy. Of the 30 patients with ischemic stroke within the
therapeutic window and meeting NIHSS criteria for thrombolysis, 20 were not
thrombolysed. Nine of these were due to administrative barriers (45%). In the
current study, the thrombolysis rate was higher than in the United States, but
barriers prevented treating 47.6% of patients with indication for thrombolysis.
Importantly, this study was conducted in a private hospital, and the situation
may be even more unfavorable in the public health system.
PMID- 24356695
TI - [Malaria in the triple border region between Brazil, Colombia and Peru].
AB - This article aims to analyze the malaria surveillance situation on the triple
border between Brazil, Colombia, and Peru. This was a qualitative study using
questionnaires in the border towns in 2011. The results were analyzed with the
SWOT matrix methodology, pointing to significant differences between the malaria
surveillance systems along the border. Weaknesses included lack of linkage
between actors, lack of trained personnel, high turnover in teams, and lack of
malaria specialists in the local hospitals. The study also showed lack of
knowledge on malaria and its prevention in the local population. The strengths
are the inclusion of new institutional actors, improvement of professional
training, distribution of insecticide-treated bed nets, and possibilities for
complementary action between surveillance systems through cooperation between
health teams on the border. Malaria control can only be successful if the region
is dealt with as a whole.
PMID- 24356696
TI - [A professional approach to family violence against the elderly in a primary
health clinic].
AB - This article aims to describe a professional approach in a primary health clinic
towards family violence against the elderly. This qualitative study collected
data through participant observation recorded in a field diary, in addition to
semi-structured interviews. Ten health workers from the clinic participated in
the interviews. Data were analyzed according to Grounded Theory, and two
categories were discussed: professional approach to domestic violence against the
elderly and the clinic's management of situations involving such violence. The
data point to professionals' difficulties in identifying violent situations and
beliefs related to the inability to cope with it. In institutional terms, the
data also highlight factors that hinder detection of cases, such as limited
emphasis on interdisciplinary work and routines focused on physical health. The
study suggests the need to offer health workers the opportunity to reflect on
domestic violence and possibilities for intervention.
PMID- 24356697
TI - [Health situation assessment by primary care workers based on geographic
information systems].
AB - Primary healthcare has made little use of information systems to assess the
population's health situation due to the difficulty in understanding the reports.
Generic definitions of actions are common, based on empirical observations. The
current study aimed to evaluate whether the introduction of georeferenced
indicators can serve to better identify individuals' health situation, which
would help planning actions by health teams. Healthcare workers from eight teams
answered a questionnaire at three different moments: the first, before reading
the information system's reports; the second after reading; and the third after
using georeferencing. The results showed a significant difference in the
classification of the health situation using georeferencing when compared to the
previous moments (p < 0.05). Georeferencing facilitated analysis of the health
situation, fostering better monitoring of work processes. Finally, use of the
data points to rationalization of actions and possible upgrading of healthcare.
The study suggests the use of georeferencing in the work agenda to become an
effective tool for orienting actions.
PMID- 24356698
TI - Ecological study on mortality from influenza and pneumonia before and after
influenza vaccination in the Northeast and South of Brazil.
AB - The study compared mortality from influenza and pneumonia in elderly people (65
years or older) before and since implementation of influenza vaccination in the
South and Northeast regions of Brazil. Official population and mortality data
were retrieved from government agencies to estimate weekly mortality rates. The
Serfling model was used to identify influenza outbreaks and estimate the
mortality attributable to them. In the South, the vaccination period showed a
major reduction in mortality from influenza and pneumonia and in the number and
duration of influenza outbreaks. These results were interpreted as consistent
with the hypothesis of the vaccination program's effectiveness. In the Northeast,
there was an increase in mortality from influenza and pneumonia during
vaccination, which was associated with a quality improvement in recording causes
of death in the elderly. An increase was also seen in mortality attributable to
influenza outbreaks, suggesting a mismatch between the period in which
vaccination is conducted and the relevant climatic characteristics for influenza
transmission.
PMID- 24356699
TI - [Semantic, item, and conceptual equivalence of the Brazilian version of the
Neighborhood Environment Walkability Scale for Youth (NEWS-Y)].
AB - The objective of this study was to describe the process of translation and
cultural adaptation of the Brazilian version of the Neighborhood Environment
Walkability Scale for Youth (NEWS-Y). The original and the Portuguese versions
were independently translated and back-translated into English. An expert panel
performed semantic analysis and conceptual adaptations. The translated version of
the NEWS-Y was applied to a sample of eight adolescents and showed adequate
understanding. After minor changes identified in the translation processes, the
expert panel considered the Brazilian version of the NEWS-Y semantically and
conceptually equivalent. The translated version of the NEWS-Y required a few
adjustments to ensure conceptual, item, and semantic adaptation. Further studies
are recommended to examine other steps in the cross-cultural adaptation of the
Portuguese-language NEWS-Y version in the Brazilian context.
PMID- 24356700
TI - [Cross-cultural adaptation of an instrument to evaluate older people's
involvement in pleasant activities].
AB - The sense of pleasure that arises from engagement in activities is a fundamental
factor for wellbeing in the elderly. Brazil lacks an instrument to evaluate older
people's involvement in pleasant activities. An American instrument was located
in the international literature (The California Older Person's Pleasant Events
Schedule - COPPES), evaluating the frequency with which older people engage in
pleasant activities and the degree of pleasure they associate with each activity.
This study's main objective was to conduct a cross-cultural adaptation (semantic,
conceptual, cultural, idiomatic, operational, and measurement equivalence) to
prepare COPPES for use in Brazil. The main results show that: (a) semantic
equivalence of the translated versus original version is satisfactory and (b) the
items are relevant to the Brazilian cultural context and evaluate the dimensions
identified by the original instrument. The new version of COPPES may contribute
to actions focused on promoting older Brazilians' wellbeing.
PMID- 24356701
TI - [Academic productivism and quantitative evaluation in graduation studies in
health: a view of harmful effects on professional training].
PMID- 24356702
TI - [The author replies].
PMID- 24356704
TI - Galectin-3 enhances epithelial cell adhesion and wound healing in rat cornea.
AB - BACKGROUND/AIMS: To investigate if galectin-3: (1) enhances adhesion of rat
corneal epithelial cells onto a collagen IV substrate and (2) promotes wound
healing in rat corneal explants. METHODS: Primary cultures of rat corneal
epithelial cells were fixed and immunostained with galectin-3 antibody. To test
cellular adherence onto plates coated with collagen type IV, isolated corneal
epithelial cells from rats were cultured for 24 h with or without recombinant
galectin-3. The attached cells were counted after fixing and staining with 0.1%
crystal violet. Direct binding of galectin-3 to collagen IV was tested using a
biotin label transfer method. To evaluate wound healing, explants with a 3.5-mm
diameter wound in the central corneal epithelium from rats were incubated for 16
h with or without recombinant galectin-3. Changes in the size of the wound were
measured with a digital microscope after staining with 5% fluorescein sodium.
RESULTS: In rat corneal epithelial cells, galectin-3 was stained throughout the
cytoplasm, with increasing density adjacent to the plasma membrane. Exogenous
galectin-3, but not epidermal growth factor (EGF), significantly promoted
adhesion of corneal epithelial cells onto the collagen IV substrate. Galectin-3
directly bound to collagen IV in vitro. Exogenous galectin-3 significantly
enhances wound healing in the corneal explants, which was partially inhibited by
beta-lactose. CONCLUSION: Galectin-3 promotes adhesion of corneal epithelial
cells onto collagen IV and enhances wound healing in corneal explants. Since
galectin-3 functions in promoting wound healing by a different mechanism than
that used by EGF, exogenous galectin-3 may be a candidate drug for enhancing
epithelial cell wound healing in disorders of the cornea.
PMID- 24356705
TI - Ten-year trend of the cumulative Helicobacter pylori eradication rate for the
'Japanese eradication strategy'.
AB - BACKGROUND/AIMS: In Japan, a systematic eradication strategy for Helicobacter
pylori has been constructed, and consists of a proton pump inhibitor/amoxicillin
and clarithromycin (PPI/AC) therapy as the first-line regimen and proton pump
inhibitor/amoxicillin and metronidazole (PPI/AM) therapy as the second-line
regimen. The cumulative rate of H. pylori eradication has not been reported.
Therefore, we investigated the annual and cumulative eradication rate to verify
the efficacy of the 'Japanese eradication strategy'. METHODS: Patients who
received first-line PPI/AC therapy and, if necessary, second-line PPI/AM therapy
between 2000 and 2009 were retrospectively analyzed. The annual cumulative
eradication rate was calculated. Data were subjected to intention-to-treat
analysis. RESULTS: PPI/AC was administered to 1973 patients (male n = 1,162,
female n = 811; mean age: 55.8 years, range: 15-87), and 250 patients received
PPI/ AM. The eradication rate for the PPI/AC regimen was 65.3%, and it gradually
but significantly decreased over 10 years (p < 0.05). For the PPI/AM regimen, the
eradication rate was 84.0%, with no change in the annual eradication rate. The
cumulative eradication rates were 76.0% in intention-to-treat analysis and 98.4%
in per-protocol analysis, respectively, which provided a consistent annual
eradication rate without decreases in effectiveness. CONCLUSION: Although the
eradication rate for the first-line PPI/AC regimen decreased over time, the
'Japanese eradication strategy' provided a sufficient eradication rate.
PMID- 24356711
TI - Non-destructive handling of individual chromatin fibers isolated from single
cells in a microfluidic device utilizing an optically driven microtool.
AB - We report a novel method for the non-destructive handling of, and biochemical
experiments with, individual intact chromatin fibers, as well as their isolation
from single cells, utilizing a specifically designed microfluidic device with an
optically driven microtool under the microscope. Spheroplasts of recombinant
fission yeast cells expressing fluorescent protein-tagged core histones were
employed, and isolation of chromatin fibers was conducted by cell bursting via
changing from isotonic conditions to hypotonic conditions in the microfluidic
device. The isolation of chromatin fibers was confirmed by the fluorescent
protein-tagged core histones involved in the chromatin fibers. For the non
destructive handling of the isolated chromatin fibers in the microfluidic device,
we developed antibody-conjugated microspheres, which had affinity to the
fluorescent protein-tagged core histones, and the microspheres were manipulated
using optical tweezers, which functioned as optically driven microtools. With the
aid of the microtool, isolated chromatin fibers were handled non-destructively
and were tethered at the microstructures fabricated in the microfluidic device
with straightened conformation by the flow. Immunofluorescence staining was
carried out as a demonstrative biochemical experiment with the individual native
chromatin fibers isolated in the microfluidic device, and specific fluorescent
spots were visualized along the tethered chromatin fibers. Thus, the potential
application of this method for epigenetic analyses of intact chromatin fibers
isolated from single cells is demonstrated.
PMID- 24356710
TI - beta-cell dedifferentiation in diabetes is important, but what is it?
AB - This commentary discusses the concept of beta-cell dedifferentiation in diabetes,
which is important but not well defined. A broad interpretation is that a state
of differentiation has been lost, which means changes in gene expression as well
as in structural and functional elements. Thus, a fully mature healthy beta cell
will have its unique differentiation characteristics, but maturing cells and old
beta cells will have different patterns of gene expression and might therefore be
considered as dedifferentiated. The meaning of dedifferentiation is now being
debated because beta cells in the diabetic state lose components of their
differentiated state, which results in severe dysfunction of insulin secretion.
The major cause of this change is thought to be glucose toxicity (glucotoxicity)
and that lowering glucose levels with treatment results in some restoration of
function. An issue to be discussed is whether dedifferentiated beta cells return
to a multipotent precursor cell phenotype or whether they follow a different
pathway of dedifferentiation.
PMID- 24356712
TI - Validation of a new objective index to measure spinal mobility: the University of
Cordoba Ankylosing Spondylitis Metrology Index (UCOASMI).
AB - Spinal mobility measures are subject to high variability and subjectivity.
Automated motion capture allows an objective and quantitative measure of mobility
with high levels of precision. To validate the University of Cordoba Ankylosing
Spondylitis Metrology Index (UCOASMI), an index measure of spinal mobility, based
on automated motion capture, validation studies included the following: (1)
validity, tested by correlation--Pearson's r--between the UCOASMI and the
mobility index Bath Ankylosing Spondylitis Metrology Index (BASMI), and a measure
of structural damage, the modified Stoke Ankylosing Spondylitis Spinal Score
(mSASSS); (2) reliability, with internal consistency tested by Cronbach's alpha,
test-retest by intraclass correlation coefficient (ICC) after 2 weeks, and error
measurement, by variation coefficient (VC) and smallest detectable difference
(SDD); and (3) responsiveness, by effect size (ES) in a clinical trial of anti
TNF. Patients for the different studies all had ankylosing spondylitis. Validity
studies show correlation between the BASMI (r = 0.881) and the mSASSS (r =
0.780). Reliability studies show an internal consistency of Cronbach's alpha =
0.894, intra-observer ICC = 0.996, test-retest ICC = 0.996, and a measurement
error of VC = 2.80% and SDD = 0.25 points. Responsiveness showed an ES after 24
weeks of treatment of 0.48. In all studies, the UCOASMI's performance was better
than that of the BASMI. The UCOASMI is a validated index to measure spinal
mobility with better metric properties than previous indices.
PMID- 24356713
TI - [Sleep medicine differential diagnostics in psychiatry and psychotherapy].
AB - Complaints about disturbed sleep or increased daytime sleepiness are among the
most frequent symptoms reported to psychiatrists by patients. Such complaints can
be symptoms of an underlying psychiatric disorder or indicative of a separate or
comorbid sleep disorder. Hence, basic knowledge in the differential diagnosis of
sleep medicine pathologies is pivotal for psychiatrists and psychotherapists. In
the present overview following a description of the diagnostic methods, the
diagnostic work-up according to the major symptomatic clusters, namely
disturbances in initiating and maintaining sleep, abnormal nocturnal movements
and excessive daytime sleepiness will be presented.
PMID- 24356714
TI - The knockout of secretin in cerebellar Purkinje cells impairs mouse motor
coordination and motor learning.
AB - Secretin (SCT) was first considered to be a gut hormone regulating
gastrointestinal functions when discovered. Recently, however, central actions of
SCT have drawn intense research interest and are supported by the broad
distribution of SCT in specific neuronal populations and by in vivo physiological
studies regarding its role in water homeostasis and food intake. The direct
action of SCT on a central neuron was first discovered in cerebellar Purkinje
cells in which SCT from cerebellar Purkinje cells was found to potentiate
GABAergic inhibitory transmission from presynaptic basket cells. Because Purkinje
neurons have a major role in motor coordination and learning functions, we
hypothesize a behavioral modulatory function for SCT. In this study, we
successfully generated a mouse model in which the SCT gene was deleted
specifically in Purkinje cells. This mouse line was tested together with SCT
knockout and SCT receptor knockout mice in a full battery of behavioral tasks. We
found that the knockout of SCT in Purkinje neurons did not affect general motor
ability or the anxiety level in open field tests. However, knockout mice did
exhibit impairments in neuromuscular strength, motor coordination, and motor
learning abilities, as shown by wire hanging, vertical climbing, and rotarod
tests. In addition, SCT knockout in Purkinje cells possibly led to the delayed
development of motor neurons, as supported by the later occurrence of key neural
reflexes. In summary, our data suggest a role in motor coordination and motor
learning for SCT expressed in cerebellar Purkinje cells.
PMID- 24356715
TI - 12-week, placebo-controlled trial of add-on riluzole in the treatment of
childhood-onset obsessive-compulsive disorder.
AB - Many children with childhood-onset obsessive-compulsive disorder (OCD) fail to
respond adequately to standard therapies. Evidence from preclinical and clinical
studies suggests that the glutamatergic neurotransmitter system might be an
alternative treatment target. This study examined the efficacy of riluzole, a
glutamatergic modulator, as an adjunctive therapy for children with treatment
resistant OCD. In a 12-week, double-blind, placebo-controlled study, 60 treatment
resistant children and adolescents (mean age=14.5 +/- 2.4 years), with moderate
to severe OCD (mean Children's Yale-Brown Obsessive-Compulsive Scale (CY
BOCS)=28.2 +/- 3.7), 17 of whom also had concomitant autism spectrum disorder,
were randomized to receive riluzole (final dose of 100 mg/day) or placebo in
addition to the existing treatment regimen. Fifty-nine subjects completed the
randomized trial. Primary outcome measures were changes on the CY-BOCS, the
Clinical Global Impressions Scale, and the Children's Global Assessment Scale.
Riluzole was fairly well tolerated, although it was associated with one case of
pancreatitis and five instances of slight increases in transaminases. All
subjects showed significant reductions in CY-BOCS scores during treatment;
however, there was no significant difference between placebo and riluzole on any
of the primary or secondary outcome measures. The study failed to demonstrate
superiority of riluzole over placebo as an adjunctive treatment for children with
childhood-onset OCD. However, future studies may show benefits for less treatment
refractory children with fewer concomitant medications.
PMID- 24356716
TI - Shape-related optical and catalytic properties of wurtzite-type CoO nanoplates
and nanorods.
AB - In this paper, we report the anisotropic optical and catalytic properties of
wurtzite-type hexagonal CoO (h-CoO) nanocrystals, an unusual nanosized indirect
semiconductor material. h-CoO nanoplates and nanorods with a divided morphology
have been synthesized via facile solution methods. The employment of flash
heating and surfactant tri-n-octylphosphine favors the formation of plate-like
morphology, whereas the utilization of cobalt stearate as a precursor is critical
for the synthesis of nanorods. Structural analyses indicate that the basal plane
of the nanoplates is (001) face and the growth direction of the nanorods is along
the c axis. Moreover, the UV-vis absorption spectra, the corresponding energy gap
and the catalytic properties are found to vary with the crystal shape and the
dimensions of the as-prepared h-CoO nanocrystals. Furthermore, remarkable
catalytic activities for H2 generation from the hydrolysis of alkaline NaBH4
solutions have been observed for the as-prepared h-CoO nanocrystals. The
calculated Arrhenius activation energies show a decreasing trend with increasing
extension degree along the <001> direction, which is in agreement with the
variation of the charge-transfer energy gap. Finally the maximum hydrogen
generation rate of the h-CoO nanoplates exceeds most of the reported values of
transition metal or noble metal containing catalysts performing in the same
reaction system, which makes them a low-cost alternative to commonly used noble
metal catalysts in H2 generation from the hydrolysis of borohydrides, and might
find potential applications in the field of green energy.
PMID- 24356717
TI - Oncolytic adenovirus-induced autophagy: tumor-suppressive effect and molecular
basis.
AB - Autophagy is a catabolic process that produces energy through lysosomal
degradation of intracellular organelles. Autophagy functions as a cytoprotective
factor under physiological conditions such as nutrient deprivation, hypoxia, and
interruption of growth factors. On the other hand, infection with pathogenic
viruses and bacteria also induces autophagy in infected cells. Oncolytic
virotherapy with replication-competent viruses is thus a promising strategy to
induce tumor-specific cell death. Oncolytic adenoviruses induce autophagy and
subsequently contribute to cell death rather than cell survival in tumor cells.
We previously developed a telomerase-specific replication-competent oncolytic
adenovirus, OBP-301, which induces cell lysis in tumor cells with telomerase
activities. OBP-301-mediated cytopathic activity is significantly associated with
induction of autophagy biomarkers. In this review, we focus on the tumor
suppressive role and molecular basis of autophagic machinery induced by oncolytic
adenoviruses. Addition of tumor-specific promoters and modification of the fiber
knob of adenoviruses supports the oncolytic adenovirus-mediated autophagic cell
death. Autophagy is cooperatively regulated by the E1-dependent activation
pathway, E4-dependent inhibitory pathway, and microRNA-dependent fine-tuning.
Thus, future exploration of the functional role and molecular mechanisms
underlying oncolytic adenovirus-induced autophagy would provide novel insights
and improve the therapeutic potential of oncolytic adenoviruses.
PMID- 24356718
TI - Factors predicting clinical impairment after surgery for cervical spinal
schwannoma.
AB - Cervical spinal schwannoma is benign, and outcomes after surgical resection are
generally excellent. A surgical dilemma sometimes arises as to whether to perform
total tumor removal, which carries a risk of sacrificing the nerve root, or
subtotal removal, where the risk can be tumor recurrence. The purpose of this
study was to identify factors with the potential to predict clinical impairment
after surgery for cervical spinal schwannomas. Thirty cases of cervical
schwannomas treated surgically in our institute were retrospectively
reviewed;initial symptoms, tumor location, Eden classification, surgical method,
functional outcome, and tumor recurrence were investigated. All permanent motor
deficits were the result of resecting functionally relevant nerve roots (i.e., C5
8). The rate of permanent sensory deficit was 11% after C1-4 nerve root
resection, and 67% after C5-8 nerve root resection. Permanent neurological
deficits occurred in 14% of patients younger than 40 years and 38% of those older
than 40. Dumbbell tumors were associated with the need for total or ventral nerve
root transection, as well as with a high incidence of tumor recurrence. The
incidence of permanent neurological deficit was significantly higher in patients
undergoing C5-8 nerve root resection, and tended to be higher in those over 40.
PMID- 24356719
TI - A new navigation system for minimally invasive total knee arthroplasty.
AB - A computer-assisted navigation system to be used for total knee arthroplasties
(TKAs) was reported to improve the accuracy of bone resection and result in
precise implant placement, but the concomitant surgical invasion and time
consumption are clinical problems. We developed a computed tomography (CT)-based
navigation system (NNS) to be used for minimally invasive TKA. It requires only
the reference points from a small limited area of the medial femoral condyle and
proximal tibia through a skin incision to obtain optical images. Here we
evaluated the usefulness and accuracy of the NNS in comparison with the
commercially available BrainLAB image-free navigation system (BLS). In a clinical
experiment, the registration times obtained with the NNS tended to be shorter
than those obtained with the BLS, but not significantly so. The NNS group tended
to be in the extended position in the sagittal plane of the distal femur within 3
degrees, and the BLS group showed rather flexed deviation in the sagittal plane
of the anterior femur.
PMID- 24356720
TI - In vitro assessment of factors affecting the apparent diffusion coefficient of
Jurkat cells using bio-phantoms.
AB - It is well known that many tumor tissues show lower apparent diffusion
coefficient (ADC) values, and that several factors are involved in the reduction
of ADC values. The aim of this study was to clarify how much each factor
contributes to decreases in ADC values. We investigate the roles of cell density,
extracellular space, intracellular factors, apoptosis and necrosis in ADC values
using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were
encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance
imaging device with constant diffusion time of 30sec. Heating at 42C was used to
induce apoptosis while heating at 48C was used to induce necrosis. Cell death
after heating was evaluated by flow cytometric analysis and electron microscopy.
The ADC values of bio-phantoms including non-heated cells decreased linearly with
increases in cell density, and showed a steep decline when the distance between
cells became less than 3MUm. The analysis of ADC values of cells after
destruction of cellular structures by sonication suggested that approximately two
thirds of the ADC values of cells originate from their cellular structures. The
ADC values of bio-phantoms including necrotic cells increased while those
including apoptotic cells decreased. This study quantitatively clarified the role
of the cellular factors and the extracellular space in determining the ADC values
produced by tumor cells. The intermediate diffusion time of 30msec might be
optimal to distinguish between apoptosis and necrosis.
PMID- 24356721
TI - High level of CXCR4 in triple-negative breast cancer specimens associated with a
poor clinical outcome.
AB - Despite high sensitivity to chemotherapy, the prognosis for triple-negative
breast cancer (TNBC) remains poor because of its high rate of metastasis and low
sensitivity to endocrine therapy. CXCR4 expression has been reported in many
subtypes of human breast cancers, but it remains unknown whether CXCR4 is
expressed in TNBC and whether CXCR4 expression in TNBC could be a prognostic
indicator. TNBCs tissues were formalin fixed, paraffin embedded and hematoxylin
eosin (H&E) stained. Immunohistochemical staining was utilized to determine the
CXCR4 expression in those specimens. Statistical analyses were performed using
SPSS16.0 software to reveal the correlation of CXCR4 expression in TNBC specimens
and cancer recurrence and cancer-related death. Our results showed that there was
a strong association between CXCR4 overexpression and both menopause and the
histological cancer grade of TNBC patients (p values were separately 0.004 and
0.001). The 5-y disease-free survival (DFS) and the 5-y overall survival (OS)
were 57.69% and 58.33% for the low-CXCR4 group versus 42.11% and 44.74% for the
high-CXCR4 group, respectively (p=0.031 and 0.048). CXCR4 overexpression plays an
important role in triple-negative breast cancers, and may be a predictor of poor
prognosis.
PMID- 24356722
TI - Coverage of the humeral head by the coracoacromial arch: relationship with
rotator cuff tears.
AB - The pathogenetic roles of the coracoacromial arch in the development of rotator
cuff tears are still controversial. This study compared the anteroposterior
coverage of the humeral head by the coracoacromial arch between shoulders with
and without full-thickness rotator cuff tears. Forty-two shoulders from 21
embalmed cadaveric specimens were macroscopically examined. Specimens were
divided into 2 groups:shoulders with full-thickness cuff tears (tear group) and
those with intact cuff tendons (normal group). The coverage angle of each
component of the coracoacromial arch was measured using true lateral photographs.
We also measured the angle of the total arc of the coracoacromial arch, as well
as the angle of the anterior acromial projection. These data were compared
between the tear group and the normal group. Although no significant differences
were observed in the total arc of the coracoacromial arch between the groups, the
tear group had significantly less coverage by the coracoacromial ligament than
did the normal group (p<0.05). Moreover, greater anterior acromial projection was
observed in the tear group (p<0.05). These results suggest that greater coverage
of the bony structures on the rotator cuff may correlate with the development of
rotator cuff tears.
PMID- 24356723
TI - Chiari type I malformation caused by craniometaphyseal dysplasia.
AB - Craniometaphyseal dysplasia is a rare genetic condition characterized by
progressive thickening of bones in the skull and metaphyseal abnormalities in the
long bones. This disorder often causes progressively symptomatic cranial nerve
compression, but in rare cases foramen magnum stenosis may lead to quadriplegia.
Chiari I malformation with craniometaphyseal dysplasia is extremely rare. The
authors report on a 25-year-old woman with myelopathy due to Chiari I
malformation along with craniometaphyseal dysplasia. There are only four previous
case reports of this condition. The authors present here the fifth case report of
this rare condition and summarize its characteristics.
PMID- 24356724
TI - Thumb polydactyly with a floating ulnar thumb.
AB - Thumb polydactyly is reported to be the most common congenital anomaly of the
hand in Japan. The floating type is not particularly rare, accounting for 0.9 to
15% of all cases of thumb polydactyly. However, to the best of our knowledge,
there has been only one case of thumb polydactyly with a floating ulnar thumb,
reported by Onizuka. Herein, we report a case very similar to that reported by
Onizuka. In our case, the vessels feeding the floating ulnar thumb branched from
the superficial palmar arterial arch, and X-rays revealed triphalangism. In
surgery, we not only reconstructed the morphology of the thumb, but also tried to
preserve the sensation in the reconstructed thumb by transposing the digital
nerve of the floating ulnar thumb to the radial thumb. In addition to thumb
polydactyly, our case also showed hypoplasia of the thenar muscles.
PMID- 24356725
TI - A case of acute superior mesenteric artery embolism with severe ischemic liver
injury successfully treated by endovascular treatment.
AB - We describe an interesting clinical course of a patient who developed severe
ischemic liver injury due to acute embolism of the superior mesenteric artery
(SMA) and celiac artery. A 70-year-old man was hospitalized for abdominal pain
and diarrhea. Abdominal computed tomography demonstrated a variant common hepatic
artery arising from the SMA and multiple thromboembolic occlusions of visceral
arteries, including the SMA and celiac artery. Laboratory data showed markedly
elevated hepatic enzymes, which increased after admission despite the initiation
of systemic anticoagulant and thrombolytic therapy. The patient was successfully
treated by endovascular recanalization of the SMA occlusion via transcatheter
embolus aspiration, thrombolysis, balloon angioplasty, and stent placement.
Severe ischemic liver injury may occur in the setting of synchronous embolism of
the SMA and celiac artery, and these phenomena may have a critical impact on the
choice of treatment strategies and prognosis. Endovascular treatment appears to
an effective treatment option.
PMID- 24356726
TI - Austrian National CathLab Registry (ANCALAR): cardiac catheterization, coronary
angiography (CA), and percutaneous coronary intervention (PCI) in Austria during
the year 2011 (Registry Data with Audit including 2012).
AB - Concerning international comparison for the year 2011, Austria is situated under
the top nations with 6,383 diagnostic coronary angiographies (CA), 2,407
percutaneous coronary interventions (PCI), and 47 transarterial aortic valve
implantations (TAVI) per 1 million inhabitants in Europe. Although the number of
TAVI increases rapidly since its first introduction in 2007 (47 TAVI per 1
million inhabitants in 2011, not including surgical cases from the transapical
route), the data for CA and PCI remained constant during the past years.The rates
of stent (91%) and drug-eluting stent implantations (78% of stents) also remained
constant on a high level. Little fluctuation is also reflected in the
complication data (including mortality evaluation). An increased morality is well
known, especially in patients with the so-called ST-segment elevation myocardial
infarction and consecutive shock (19-35% in the past years).The application of
certain special devices increased (clot catcher) or decreased (glycoprotein
IIb/IIIa receptor antagonist) in 2011 or were finally unused
(Laser).Interestingly, not only in Austria, it was observed several times that
scientific knowledge, recommended as Class I Indications in the guidelines, takes
several years to establish itself nationwide.Our independent, purely academic
activity is located in the area of health services research, and has also the
option to generate benchmarks for individual centers. Participation in our
surveys is voluntary. Since 1992, every year, without interruption (no missing
center!), 90-100 parameters are applicable. The questionnaire will be optimized
and adapted to current conditions. This is done in cooperation with the
participating centers. To provide comparability, we make only minimal and
absolutely most necessary modifications.The data are collected and summarized at
the end of the year by each center itself. During the year, the centers are
visited to perform audits and to keep personal contact to them.The data for 2011
were presented in Linz (November 23, 2012) at the autumn meeting of the working
group "Interventional Cardiology of the Austrian Society of Cardiology" (OKG), as
a basis for discussion. The presentation can be viewed by using private access
code to the OKG video presentation page ( http://oekg.medroom.at/ ); the
publication will also be placed under the website http://iik.i-med.ac.at.
PMID- 24356727
TI - Alcohol-induced changes in methylation status of individual CpG sites, and serum
levels of vasopressin and atrial natriuretic peptide in alcohol-dependent
patients during detoxification treatment.
AB - Disturbances of volume-regulating peptides like vasopressin (AVP) and atrial
natriuretic peptide (ANP) have been described in early abstinent alcohol
dependent patients. In a longitudinal approach, we investigated whether changes
in AVP and ANP serum levels correlated to cytosine-phosphatidyl-guanine (CpG)
methylation of the respective gene promoters on days 1, 7 and 14 of alcohol
withdrawal. We analyzed the blood samples of 99 patients suffering from alcohol
dependence alongside age- and BMI-matched controls. Concerning AVP promoter
methylation, we observed an interaction between time of measurement and CpG loci
with CpG 2 showing a significant increase in methylation from day 1 to 14. Serum
levels of AVP were significantly decreased in the patient group. Compared to
healthy controls, promoter-related DNA methylation of the ANP promoter was
significantly reduced on days 7 and 14. Moreover, we detected a significant
interaction between CpG position and group. In both cases the difference was
mainly observed at CpG 1. The present study shows significant changes in the
methylation status of individual CpG sites of AVP and ANP. Observing respective
alterations of AVP serum protein levels in alcohol-dependent patients during
detoxification treatment, we consider methylation as a possible mode of
regulation for these proteins during alcohol detoxification.
PMID- 24356728
TI - Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma
cell differentiation mediated by XBP-1.
AB - The unfolded protein response (UPR) is an essential pathway for both normal and
malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in
response to the large amount of immunoglobulin (Ig) output. The inositol
requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway
has been shown to play crucial roles not only in relieving the ER stress by up
regulating a series of genes favoring ER-associated protein degradation and
protein folding, but in mediating terminal plasmacytic differentiation and
maturation. Myeloma cells comprise various subsets arrested in diverse
differentiated phases, and the immaturity of myeloma cells has been taken as a
marker for poor prognosis, suggesting that differentiation induction would be a
promising therapeutic strategy for myeloma. Herein, we used low-dose
pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to
efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by
transcriptional expression increase in spliced XBP-1 and molecular chaperons,
accompanied by significant differentiation and maturation of these myeloma cells,
without concomitant cytotoxicity. These differentiated myeloma cells exhibited a
more mature appearance with well-developed cytoplasm and a reduced
nucleocytoplasmic ratio, and a further differentiated phenotype with markedly
increased expression of CD49e together with significantly elevated cellular
secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to
the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown
of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and
maturation. Our study, for the first time, validated that the modest activation
of the UPR pathway enables myeloma cells to further differentiate, and identified
that XBP-1 plays an indispensable role in UPR-mediated myeloma cell
differentiation and maturation. Thus, we provided the rationale and feasibility
for the exploration of the novel therapeutic strategy of differentiation
induction for plasmacytic malignancies.
PMID- 24356730
TI - [Teaching of clinical reasoning to medical students using prototypical clinical
cases].
AB - BACKGROUND: Clinical reasoning is the most important competente in the training
process of a physician. AIM: To develop a method for teaching clinical reasoning
based on prototypes of clinical cases. MATERIAL AND METHODS: The study was
conducted on sixty-four third year medical students. The study and control groups
attended lectures and tutorial sessions with patients. The study group attended
additionally discussion seminars of prototypical clinical cases. A clinical
reasoning test was applied at the start and end of the learning period to both
groups. At the end of the study, the opinions of students of the study group were
collected in a focus group. RESULTS: After the learning period, both groups
significantly increased their clinical reasoning skills. However, the improvement
in the study group was more than double than that of the control group. The
absolute improvement in the study group was 30.9%. Students interviewed in the
focus group were unanimous in expressing their satisfaction in each and every
aspect discussed. CONCLUSIONS: The teaching of clinical reasoning to third year
medical students by means of pattern recognition in seminars with clinical cases
improved significantly their skills.
PMID- 24356729
TI - Are healthcare workers immune to rubella?
AB - Healthcare workers (HCW) have high exposure to infectious diseases, some of
which, such as rubella, are vaccine-preventable. The aim of this study was to
determine the immunity of HCW against rubella. We performed a seroprevalence
study using a self-administered survey and obtained blood samples to determine
rubella Immunoglobulin G (IgG) antibody levels in HCW during preventive
examinations by five Primary Care Basic Prevention Units and six tertiary
hospitals in Catalonia. Informed consent was obtained. IgG was determined using
an antibody capture microparticle direct chemiluminometric technique. The odss
ratio (OR) and 95% confidence intervals (CI) were calculated. Logistic regression
was made to calculate adjusted OR. Of 642 HCW who participated (29.9% physician,
38.8% nurses, 13.3% other health workers and 18% non-health workers), 46.6% were
primary care workers and 53.4% hospital workers. Of total, 97.2% had rubella
antibodies. HCW aged 30-44 years had a higher prevalence of antibodies (98.4%)
compared with HCW aged<30 years (adjusted OR 3.92; 95% CI 1.04-14.85). The
prevalence was higher in nurses than in other HCW (adjusted OR: 5.57, 95% CI 1.21
25.59). Antibody prevalence did not differ between females and males (97.4% vs.
97.1%, P 0.89), type of center (97.7% vs. 96.8%, P 0.51) or according to history
of vaccination (97.3% vs. 96.8%, P 0.82). Seroprevalence of rubella antibodies is
high in HCW, but workers aged<30 years have a higher susceptibility (5.5%).
Vaccination should be reinforced in HCW in this age group, due to the risk of
nosocomial transmission and congenital rubella.
PMID- 24356731
TI - [Long-term survival of immunocompetent patients older than 60 years hospitalized
for community-acquired pneumonia].
AB - BACKGROUND: A reduction in long-term survival of adult patients hospitalized with
community-acquired pneumonia (CAP), especially older people with multiple
comorbidities, has been reported. AIM: To examine the clinical variables
associated to mortality at 72 months of adult patients older than 60 years
hospitalized with CAP and compare their mortality with a control group matched
for age, gender and place of admission. MATERIAL AND METHODS: Prospective
assessment of 465 immunocompetent patients aged 61 to 101 years, hospitalized for
CAP in a teaching hospital. Hospital and 30 day mortality was obtained from
medical records. Seventy two months survival of the 424 patients who were
discharged olive, was compared with a group of 851 patients without pneumonia
paired for gender and age. Mortality at 72 months was obtained from death
certificates. RESULTS: Eighty seven percent of patients had comorbidity. The
median hospital length of stay was 10 days, 8.8% died in the hospital, 29.7% at
one year follow-up and 61.9%o at 6 years. The actuarial survival at six years was
similar in the cohort of adults hospitalized with CAP and the control group
matched for age, gender and site of care. In a multivariate analysis, the
clinical variables associated with increased risk of dying during long-term
follow-up were older age, chronic cardiovascular and neurological diseases,
malignancy, absence of fever, low C-reactive protein at hospital admission and
high-risk parameters of the Fine index. CONCLUSIONS: Advanced age, some specific
comorbidities, poor systemic inflammatory response at admission and high risk
parameters of the Fine Index were associated to increased risk of dying on long
term follow-up among older adults hospitalized for CAP.
PMID- 24356732
TI - [Comparison between CHOP-like and R-CHOP in diffuse large B cell and follicular
lymphoma].
AB - BACKGROUND: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large
B cell (DLBCL) and follicular (FL). AIM: To analyze the benefit of Rituxi-mab in
overall survival (OS) of patients with NHL. MATERIAL AND METHODS: Review of
medical record of 230 adult patients with a first episode of NHL admitted between
2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL.
RESULTS: The overall response (OR) was 64% with 39% complete remissions (CR) in
DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with
CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a
statistically significant difference in median event-free survival (EvFS) in
favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p =
0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%)
with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36
months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures
for patients treated with CHOP-like were 80 and 66%> respectively. The
progression free survival (PFS) was 21 months with CHOP-like versus not attained
with R-QT (p = 0,043). CONCLUSIONS: When Rituximab was added to CHOP, there was a
higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.
PMID- 24356733
TI - [Opinion survey on the use of assisted reproductive technologies applied to
inhabitants of Santiago, Chile].
AB - BACKGROUND: Advances in reproductive medicine and the use of assisted
reproductive technologies (ART) have a great impact in the lives of people and
the conformation of their families. AIM: To report the results of an opinion
survey applied to inhabitants of Santiago, Chile about the use of ART to
conceive. MATERIAL AND METHODS: A survey was designed and applied to a random
representative sample of 1.500 people between the ages of 18 and 65 in the 34
municipalities of Santiago. RESULTS: Eighty eight percent of respondents support
the use of medical assistance to conceive children. Wide approval exists for the
use of in vitro fertilization (IVF) by heterosexual couples, even when not
married (85.9%) and by single women (70.4%), by both mole and female participants
of every socioeconomic level, age group and religious affiliation. Support
decreases significantly when the use of IVF is considered for post-menopausal
women (35.1 %) and by same-sex couples (26.6%). CONCLUSIONS: Results of this
survey indicate that the majority of inhabitants in Santiago favor the use of
ART, including IVF. This support decreases significantly for elderly women and
homosexual couples.
PMID- 24356734
TI - [Influence of the referring health care systems and other factors on the results
of mitral valve replacement].
AB - BACKGROUND: There is no consensus regarding which risk factors influence the
outcome of mitral valve replacement. AIM: To study the effects of the referring
health care system and other factors on the results of mitral replacement.
PATIENTS AND METHODS: We included 632 patients operated between 1990 and 2010
receiving the St Jude prosthesis. Patients were divided into three groups, group
1 composed by 180 patients coming from the Public System, group 2 composed by 182
patients coming from the University System and group 3 composed by 270 patients
coming from the Private System. RESULTS: Overall operative mortality was 4.3%.
There was no difference between groups in mortality. Factors responsible for
operative mortality were: emergency operation (Odds Patio (OR): 5.6 P < 0.01) and
left ventricular function (according to ejection fraction) grade III to IV (OR:
2.5 p = 0.048). Actuarial survival rates at 1, 5, 10, 15 and 20 years were 95%,
87%, 76%, 61% and 41%, respectively. Risk factors for long-term mortality were
diabetes (OR: 3.3 p < 0.01), left ventricular function grades III-IV (OR: 2.6 p <
0.01), New York Heart Association functional class III to PV (OR: 2.1 p < 0.005)
and male sex (OR: 1.5 p < 0.032). CONCLUSIONS: Referring health care system and
type of surgery do not constitute a risk factor for mitral replacement. Risk
factors were: emergency surgery, ventricular function grades III-IV, diabetes,
functional capacity class III-IV and male sex. Integration of public and private
health care systems in a university hospital setting achieves excellent outcomes
for complex pathology.
PMID- 24356735
TI - [Achievement of cardiovascular prevention goals, pharmacologic prescription and
major cardiovascular events among patients with coronary disease].
AB - BACKGROUND: Implementation of health programs to reduce cardiovascular risk, are
needed for secondary prevention of cardiovascular diseases. AIM: To evaluate
achievements of secondary prevention goals, pharmacologic prescription and major
cardiovascular events in patients with coronary artery disease. MATERIAL AND
METHODS: Patients who had a first event of acute coronary syndrome, angioplasty
or revascularization surgery, between January 2008 and June 2010, were contacted
for a clinical and laboratory evaluation between June and October 2011. RESULTS:
Seven hundred and two medical records were reviewed and 245 eligible patients
were identified. Of these, we assessed 202 patients aged 64 +/- 10 years (70%
males). Sixty seven percent had two or more cardiovascular risk factors. A goal
of HDL cholesterol level over 40 mg/dL was achieved in 91 % of patients, smoking
cessation in 84% and a total cholesterol < 200 mg/dL in 66%. A blood pressure
below 130/85 mm Hg was achieved in 30% of patients, a normal BMI in 19% and LDL
cholesterol levels below 70 mg/dL in 18%. At the moment of assessment, 87%> were
using aspirin, 78%> statins, 74% angiotensin converting enzyme inhibitors or
angiotensin II receptor antagonists and 66%o were using beta--blockers. Twenty
two percent of patients had a major cardiovascular event during the follow up,
which lasted 28 +/- 8 months. CONCLUSIONS: A low percentage of cardiovascular
goals achievement was observed in this sample of patients, with a high prevalence
of overweight and obesity. A high percentage quit smoking after their first
cardiovascular event. Despite the high percentage of drug prescription,
hypertension and dyslipidemia were not fully controlled.
PMID- 24356736
TI - [Receiving the diagnosis of Down syndrome: what do the parents think?].
AB - BACKGROUND: Having a child with Down syndrome (DS) is usually unexpected and
stressful. AIM: To describe the experiences of parents of children with DS at the
time of diagnosis. MATERIAL AND METHODS: A self-administered survey was answered
by 345 parents (62% women) with an offspring with DS. RESULTS: Eighty four
percent of parents received a postnatal diagnosis of DS, 32.3% were informed of
the diagnosis in the presence of his or her partner and 19.3%o received some form
of printed material regarding DS. Fifty six percent of respondents considered
that the delivery of the diagnosis was inadequate. Factors associated with an
overall positive experience were prenatal diagnosis (Odds Ratio (OR) 3.91 (95%
Confidence Intervals (CI) 2.06-7.44)) and the presence of both parents at the
time of the delivery of the diagnosis (OR 1.84 (95%> CI 1.16-2.91)). Fifty three
percent of respondents believe that prenatal diagnosis of DS is preferable.
CONCLUSIONS: The majority of parents are unsatisfied with the way the diagnosis
of DS is delivered. Efforts should be made to educate health personnel regarding
the delivery of the diagnosis of SD, to foster opportunities for prenatal
diagnosis and to improve the delivery of printed material.
PMID- 24356737
TI - [Hepcidin as a central mediator of anemia of chronic diseases associated with
obesity].
AB - Recent evidence suggests that obesity-related inflammation may play a central
role in hepcidin regulation. Hepcidin is a key regulator ofiron homeostasis and
has now been suggested as a central mediator ofiron metabolism disorders involved
in the pathogenesis of anemia of chronic disease. In this review, we focus on
subclinical inflammation in obesity and its effect on hepcidin levels, as the
most plausible explanation for the relationship between anemia of chronic disease
and obesity.
PMID- 24356738
TI - [Uric acid and purine plasma levels as plausible markers for placental
dysfunction in pre-eclampsia].
AB - Uric acid is the final metabolite of purine break down, such as ATP, ADP, AMP,
adenosine, inosine and hypoxanthine. The metabolite has been used broadly as a
renal failure marker, as well as a risk factor for maternal and neonatal
morbidity during pre-eclamptic pregnancies. High purine levels are observed in
pre-eclamptic pregnancies, but the sources of these purines are unknown. However,
there is evidence that pre-eclampsia (mainly severe pre-eclampsia) is associated
with an increased release of cellular fragments (or microparticles) from the
placenta to the maternal circulation. These in fact could be the substrate for
purine metabolism. Considering this background, we propose that purines and uric
acid are part of the same physiopathological phenomenon in pre-eclampsia (i.e.,
placental dysfunction) and could become biomarkers for placental dysfunction and
postnatal adverse events.
PMID- 24356739
TI - [The manuscripts' review process in Revista Medica de Chile and its peer
reviewers during the year 2012].
PMID- 24356740
TI - [Serum levels of alanine aminotransferase in Chilean population: analysis of
results of the national health survey 2009-2010].
AB - BACKGROUND: Determination of Alanine aminotransferase serum levels ([ALT]s) is a
sensitive ana reliable test for liver diseases. AIM: To report the prevalence of
abnormal [ALT]s in Chilean population and to identify associated variables.
METHODS: We analyzed data from a random sub-sample of 2,794 adults surveyed
during the second Chilean National Health Survey. Abnormal [ALT]s were defined by
using three different cut-off values (COV), two fixed COV (COV1: > 30 IU/L in men
and > 19 IU/L in women and COV2 pre-defined by the performing laboratory) and a
COV adjusted by age, weight and sex (COV3 > 31 IU/L for women and > 44 IU/L and
men > 42 IU/L and > 66 IU/L with a BMI > 23). Logistic regression analysis was
performed to determine risk factors for elevated [ALT]s. RESULTS: Mean [ALT]s
values were 30.14 I U/L in men and 22.03 IU/L in women. The observed prevalence
of abnormal [ALT]s defined by different COV were 38%, 11.5%, and 8.1% for COV1,
COV2 and COV3 respectively. Variables independently associated to abnormal [ALT]s
in a multivariate analysis were the following: serum gamma-glutamyl
transpeptidase (OR: 1.055 [95% CI 1.033-1.078]) and body mass index (OR:1.13 [95%
CI 1.09-1.17]). Variables inversely associated with abnormal [ALT]s (COV1) were
mole gender (OR-.0.976 [95% CI 0.96-0.99) and HDL-cholesterol (OR:0979 [95% CI
0.96-0.99]). CONCLUSIONS: Independently of the COV used, Chilean population
exhibits a high prevalence of abnormal [ALT]s which may reflect a significant
burden of liver disease. Non-alcoholic fatty liver disease could be a major
contributor to elevated [ALT]s considering the association of abnormal [ALT]s and
metabolic variables.
PMID- 24356741
TI - [Acute hepatitis due to infectious mononucleosis in a 21-year-old-man].
AB - A 21-year-old mole was admitted because of fever, fatigue, headache, pharyngitis,
abdominal pain, loss of appetite, vomiting and dark urine for three days. The
patient denied recent use of medicines or any other drug. His physical
examination disclosed jaundice, hepato-splenomegaly, whitish-yellow covered
tonsils, bilateral anterior and posterior cervical lymph node enlargement
associated with edema on the face and neck. Routine blood tests detected
abnormalities in serum bilirubins and liver enzymes (total bilirubin: 14.5 mg/dl,
direct-reacting bilirubin: 12.9 mg/dl, AST: 697 U/l, ALT: 619 U/l, alkaline
phosphatases: 260 U/l, and GGT: 413 U/l). Serological tests showed negative
results for viral hepatitis, cytomegalovirus, HIV-1 and HIV-2, and toxoplasmosis
markers, while serology for recent infection by EBV was positive (IgM: 70 and 29
U/ml; EBV IgG: 25 and 156 U/ml). Although infrequently, EBV infection can cause
acute hepatitis with accentuated cholestatic jaundice (5% of cases), which may
constitute an additional diagnostic challenge for primary care physicians. The
patient improved with supportive management and was discharged after 12 days.
This case study might contribute to increase the suspicion index about acute
hepatitis related to EBV.
PMID- 24356742
TI - [Hughes-Stovin syndrome: report of one case].
AB - We report a 25 year old mole admitted to a critical care unit for fever, lung
opacities and acute respiratory failure. A chest angio-CAT sean showed multiple
pulmonary artery aneurysms. A deep venous thrombosis of both lower limbs was also
documented. A Hughes-Stovin syndrome was postulated. An inferior vena cava filter
was placed. The patient received antimicrobial therapy subsiding fever and
respiratory failure. Subsequently, he was treated with intravenous and oral
steroids and one dose of cyclophosphamide. The patient was discharged in good
conditions fifteen days after admission.
PMID- 24356743
TI - [Gastric lipoma removed by laparoscopic subtotal gastrectomy: report of one
case].
AB - Gastric lipoma is a rare benign gastric tumor. We report a 62-year-old man, who
presented with abdominal pain, vomiting and weight loss. An upper
gastrointestinal endoscopy showed a gastric antral, submucosal tumor. Abdominal
ultrasound and computed tomography revealed a large antral lesion with content of
high echogenicity and fat density, measuring 11 x 6 cm. The patient was treated
with a laparoscopic distal subtotal gastrectomy, and a Roux-en-Y reconstruction.
The patient had no postoperative morbidity, was started on a liquid diet on the
third postoperative day and was discharged on the third postoperative day. The
pathological study revealed a gastric lipoma with clear margins. This
laparoscopic procedure represents a good alternative in the treatment of this
benign gastric tumor.
PMID- 24356744
TI - [Effectiveness of mesh inguinal hernia repair: a systematic review].
AB - There is controversy about the effectiveness of mesh techniques for inguinal
hernia repair (IHR) when compared with non-mesh procedures. The aim of this study
was to systematically review the available evidence on the effectiveness of mesh
compared to non-mesh IHR techniques. Cochrane Central and MEDLINE databases and
the TRIP Database engine were reviewed looking for systematic reviews (SR) and
clinical trials (CT) published from 1990 to 2012, comparing the effectiveness, in
terms of operative time, postoperative pain, morbidity, hospital stay, return to
work, costs and recurrence, of mesh and non-mesh IHR techniques. We retrieved
3,069 articles, 17 of which met the selection criteria (3 SR and 14 RCT),
representing a population of 15,124 subjects (7361 mesh and 7763 non-mesh IHR).
According to these studies, mesh IHR techniques are associated with less surgical
time, pain, hospital stay, recurrence and sooner return to work than non-mesh
techniques. It is concluded that mesh techniques are more effective than those
not using a mesh.
PMID- 24356745
TI - [The papers' pilgrimage].
PMID- 24356746
TI - [Hipolito Unanue, M.D. A father of Peruvian medicine and science].
PMID- 24356747
TI - Droplet array on local redox cycling-based electrochemical (LRC-EC) chip device.
AB - We have previously reported a local redox cycling-based electrochemical (LRC-EC)
system for the incorporation of many electrochemical sensors into a small chip
device. In the present study, a new type of LRC-EC chip device was fabricated for
the detection of a droplet array. To detect electrochemically redox compounds in
droplets, Pt pseudo-reference/counter electrodes were incorporated into the
individual sensors of the LRC-EC chip device. Cyclic voltammetry for the LRC-EC
chip device with internal Pt pseudo-reference electrodes indicated well-defined
voltammograms based on redox cycling for the individual sensor points. The device
was successfully applied to the addressable detection of alkaline phosphatase
(ALP) activity of HeLa cells in single droplets on the sensor points. Therefore,
the LRC-EC chip device is considered to be a useful device for the bioanalysis of
droplet systems.
PMID- 24356748
TI - Role of vesicle-associated membrane protein 2 in exocytosis of glucagon-like
peptide-1 from the murine intestinal L cell.
AB - AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1), secreted by the enteroendocrine
L cell, is an incretin hormone that potently stimulates insulin secretion.
Although signalling pathways promoting GLP-1 release are well characterised, the
mechanisms by which GLP-1-containing granules fuse to the L cell membrane are
unknown. As soluble NSF attachment proteins (SNAREs) are known to mediate granule
membrane fusion, the role of vesicle-associated membrane proteins (VAMPs) in GLP
1 exocytosis was examined. METHODS: SNARE expression was determined in murine
GLUTag L cells by RT-PCR and immunoblot and in primary murine L cells by
immunofluorescence. Co-immunoprecipitation was used to examine SNARE
interactions, while tetanus toxin (TetX)-mediated cleavage of VAMP was used with
a GLP-1 secretion assay and total internal reflection fluorescence microscopy to
determine the role of VAMP2 in exocytosis. RESULTS: VAMP2 was expressed in murine
L cells and localised to secretory granules in GLUTag cells. VAMP1/3 and the core
membrane proteins syntaxin1a and synaptosomal-associated protein 25 kDa (SNAP25)
were also detected. TetX cleaved VAMPs in GLUTag cells. However, only VAMP2
interacted with syntaxin1a, as did SNAP25 and Munc18-1. TetX treatment of GLUTag
cells prevented glucose-dependent insulinotrophic peptide- and oleic-acid
stimulated GLP-1 secretion (p < 0.05-0.01), as well as K(+)-stimulated single
cell exocytosis (p < 0.05-0.001), while TetX-resistant VAMP2 expression rescued
GLP-1 secretion (p < 0.01-0.001). CONCLUSIONS/INTERPRETATION: Together, these
findings indicate an essential role for VAMP2 in GLP-1 exocytosis from the GLUTag
L cell in response to a variety of established secretagogues. An improved
understanding of the mechanisms governing the release of GLP-1 may lead to new
therapeutic approaches to enhance the levels of this incretin hormone in patients
with type 2 diabetes.
PMID- 24356750
TI - Insomnia in the community.
AB - Insomnia is the most common sleep complaint encountered in primary care. It
affects both the individual and society through the burden of medical,
psychiatric, interpersonal and social consequences. The management of patients
affected by insomnia depends on the accurate diagnosis of the condition,
consideration of the possible aetiologies, the duration of the insomnia and its
impact on both the individual and society. Herein, we discuss the appropriate
management of insomnia in the community.
PMID- 24356749
TI - Search for genetic determinants of sulfonylurea efficacy in type 2 diabetic
patients from China.
AB - AIMS/HYPOTHESIS: The aim of this study was to investigate whether genetic
variance can influence the efficacy of glibenclamide in patients with type 2
diabetes. METHODS: A total of 747 patients with type 2 diabetes was enrolled from
the Xiaoke Pills Clinical Trial, which is a double-blind, randomised controlled
trial. All the patients had been treated with glibenclamide for 48 weeks, with
strict drug dose adjustment and data collection. Treatment failure was confirmed
when patients reached the criteria for terminating their participation in the
study (fasting blood glucose level >= 7.0 mmol/l on two consecutive tests 4 weeks
after reaching the pre-set maximal dose or maximal tolerated dose). Using this
cohort, we tested 44 single-nucleotide polymorphisms (SNPs) in 27 gene regions.
The genes in our study were involved in the metabolism of sulfonylureas, islet
beta cell function, insulin resistance and beta cell growth and differentiation.
A logistic regression model was used to evaluate the relationship between genetic
variants and treatment failure over a period of 48 weeks. RESULTS: We found that
no SNP reached the significance level of p < 0.00125 if Bonferroni correction was
performed for multiple testing in the logistic regression model used in this
pharmacogenetic study. Participants with the minor allele C of rs10811661 in
CDKN2A/CDKN2B showed a significantly greater reduction in fasting blood glucose
(TT vs TC vs CC: 9.3% (0-20.0%) vs 9.2% (0.9-20.5%) vs 12.7% (5.2-24.4%), p =
0.008) after the initial 4 weeks of treatment independent of age, sex and BMI.
There was a significant difference in beta cell function among carriers of
different genotypes of rs10811661. CONCLUSIONS/INTERPRETATION: Our study
demonstrated that the CDKN2A/CDKN2B gene may be nominally associated with the
efficacy of glibenclamide, and that CDKN2A/CDKN2B is associated with beta cell
function.
PMID- 24356751
TI - Clinics in diagnostic imaging (150).
AB - Spontaneous spinal epidural haematoma is a rarely encountered cause of back pain.
It often leads to cauda equina syndrome, necessitating emergency spinal surgery.
We report the case of a 19-year-old Chinese man who presented with pain in the
lower back, which started after he had carried some heavy boxes. He denied a
history of fall or trauma. Magnetic resonance (MR) imaging showed a hyperintense
biconvex-shaped lesion in the posterior epidural space on both T1- and T2
weighted sequences, diagnostic of a spinal epidural haematoma. The patient, who
was admitted and managed conservatively, had gradual resolution of his pain. No
neurological deficit was detected on discharge or on follow-up. Repeat MR imaging
showed total resolution of the lumbar spinal epidural haematoma. The clinical
characteristics, MR imaging features, diagnosis and management of spontaneous
spinal epidural haematoma are discussed.
PMID- 24356752
TI - Re-emergence of chronic obstructive pulmonary disease: it is time to think
COPDifferently.
AB - Knowledge of chronic obstructive pulmonary disease (COPD) as a common,
preventable and treatable condition has advanced in the last two decades, as
evidenced by the increase in scientific literature. Tobacco smoking still remains
a predominant risk factor for COPD. Thus smoking cessation management should be
obligatory in every case. Although spirometry is integral to the diagnosis of
COPD, one should also be aware of its limitations. COPD is a chronic disease
associated with comorbidities that define its extrapulmonary manifestations.
Systemic inflammation provides the biological link, while exacerbations play a
prominent role in the current approach to disease evaluation. This paper reviews
the latest Global Initiative for Chronic Obstructive Pulmonary Disease revision,
focusing on the paradigm shift in assessment that would directly influence
therapeutic decisions. Also discussed are the newer drugs and combinations of
existing inhaler therapies that now present clinicians with more options, as well
as bronchoscopic interventions that may perhaps offer a lower-morbidity
alternative than surgical lung volume reduction. Finally, this review highlights
how integrated care models can bridge the gap between components and complete a
comprehensive sphere of COPD care.
PMID- 24356753
TI - Compliance with noninvasive home ventilation in children with obstructive sleep
apnoea.
AB - INTRODUCTION: This study aimed to determine compliance with noninvasive home
ventilation in children with obstructive sleep apnoea and the factors affecting
this compliance. METHODS: We retrospectively reviewed 51 children who were
prescribed noninvasive home ventilation for the management of obstructive sleep
apnoea from 1 January 2000 until 31 May 2008. Noninvasive ventilation was started
based on positive polysomnogram, i.e. obstructive apnoea hypopnea index >= 1/hr.
Compliance was defined as the use of noninvasive ventilation >= 4 days/week.
RESULTS: Noninvasive home ventilation was started at a median age of 11.5 years.
In all, 21 (41.2 %) children were reported to be compliant with treatment.
Univariate analysis revealed that the female gender (p = 0.017), presence of
asthma (p = 0.023), presence of genetic syndromes (p = 0.023), use of bi-level
ventilation versus continuous positive airway pressure (p = 0.027), and funding
from the social work department (p = 0.049) were associated with compliance with
noninvasive home ventilation. Logistic regression revealed the presence of asthma
(p = 0.008) and female gender (p = 0.047) to be significantly associated with
compliance with treatment. However, factors such as counselling prior to
initiation of treatment, severity of obstructive sleep apnoea before initiation
of treatment, obesity, use of humidification, and polysomnogram indices were not
found to be associated with treatment compliance. CONCLUSION: Only 41.2% of the
children in this study were reported to be compliant with noninvasive home
ventilation. The female gender and the presence of asthma were associated with
treatment compliance. Future research focusing on effective methods to improve
compliance with noninvasive home ventilation in children should be undertaken.
PMID- 24356754
TI - Total laparoscopic Wertheim's radical hysterectomy versus Wertheim's radical
abdominal hysterectomy in the management of stage I cervical cancer in Singapore:
a pilot study.
AB - INTRODUCTION: For many decades, Wertheim's radical hysterectomy via laparotomy,
also known as Wertheim's radical abdominal hysterectomy (RAH), has been the
traditional surgical approach for operable stage IB cervical cancer. However,
many established cancer centres worldwide have recently shown total laparoscopic
Wertheim's radical hysterectomy (TLRH) to be a safe and feasible alternative to
the conventional abdominal route for early cervical cancer management. This
technique was introduced in Singapore in 2009. METHODS: This was a prospective
pilot study comparing TLRH with RAH in a single large tertiary institution in
Singapore. Inclusion criteria included surgically fit patients with early
cervical cancer and no radiological evidence of regional or distant metastases.
RESULTS: From November 2009 to February 2011, a total of 18 TLRHs and 30 RAHs
were performed. The median blood loss in the TLRH group was significantly lower
than that in the RAH group (300 mL vs. 500 mL; p = 0.04). However, there was no
statistically significant difference found between the two techniques in terms of
operative time, hospital stay, bladder recovery, total lymph node yield or
adjuvant treatment. No intraoperative bladder, ureteric or bowel complications
were observed in the two groups. Postoperative complications occurred in 2
(11.1%) TLRH patients and 4 (13.3%) RAH patients. With a median follow-up of 37.3
(range 10-68) weeks, the rate of recurrence was found to be 5.6% for the TLRH
group and 10.0% for the RAH group. CONCLUSION: The results of our study suggest
that with appropriate patient selection and increased experience, TLRH can be a
safe and effective procedure for the management of early cervical cancer in
Singapore.
PMID- 24356755
TI - Efficacy of target-controlled infusion of propofol and remifentanil with high
frequency jet ventilation in fibre-optic bronchoscopy.
AB - INTRODUCTION: Sedation or anaesthesia is recommended for all patients undergoing
bronchoscopy unless absolute contraindications exist. However, the widely used
combination of propofol and opiates for moderate sedation (MS) in bronchoscopy
results in a high incidence of hypoxaemia and a relatively high cough score
during the procedure. In this study, we evaluated the efficacy and safety of
target-controlled infusion (TCI) of propofol and remifentanil, together with the
use of high frequency jet ventilation (HFJV), to achieve general anesthesia (GA)
in diagnostic fibre-optic bronchoscopy. METHODS: A total of 92 consecutive
patients scheduled for flexible bronchoscopy were randomly assigned to receive
either MS using TCI-delivered propofol and remifentanil (n = 46), or GA using TCI
delivered propofol and remifentanil with HFJV (n = 46). The following were
compared between the MS and GA groups: incidence of hypoxaemia, cough score,
haemodynamic parameters, partial pressure of carbon dioxide in arterial blood,
duration of bronchoscopy and patient satisfaction score. RESULTS: The average and
minimum oxygen saturation values in the MS group were lower than those in the GA
group. The MS group showed a higher incidence of hypoxaemia. There was no
significant difference in the partial pressure of carbon dioxide between the two
groups. Cough score and duration of the bronchoscopy were markedly lower in the
GA group, and patient satisfaction score was higher in the GA group. CONCLUSION:
GA, achieved via TCI-delivered propofol and remifentanil with HFJV, provides
better conditions for diagnostic bronchoscopy - it decreases the occurrence of
hypoxaemia, shortens the duration of bronchoscopy and increases patient
satisfaction.
PMID- 24356756
TI - Determinants of sexual intercourse initiation among incarcerated adolescents: a
mixed-method study.
AB - INTRODUCTION: This study aimed to investigate the determinants of sexual
intercourse initiation among incarcerated adolescents aged 12-19 years in
Malaysia. METHODS: This was a sequential mixed-method research project that was
conducted in two phases. Quantitative and qualitative methods were used in the
first and second phases, respectively. Data was collected via a survey using self
reported questionnaires from 1,082 adolescents, and from in-depth interviews and
the written essays of 29 participants. The participants were recruited from 22
welfare institutions in peninsular Malaysia. RESULTS: Among the study
participants, 483 were male and 599 were female. Overall, 62.3% of the
incarcerated adolescents had initiated sexual intercourse at least once. The mean
age at first sexual intercourse for both genders was 14.0 years. Individual
factors found to be associated with previous sexual intercourse were the female
gender (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.11-2.74), previous
alcohol use (OR 1.80; 95% CI 1.10-2.94), previous illicit drug use (OR 1.85; 95%
CI 1.07-3.22), permissive attitude toward premarital sex (OR 4.34; 95% CI 2.17
8.70), and sexual abuse during childhood (OR 5.41; 95% CI 3.52-8.32). Qualitative
findings revealed that the reasons for initiation of sexual intercourse among
these adolescents were partner influence, inability to control sex drive, family
issues, and the perception of sex as an expression of love. CONCLUSION: The
determinants of sexual intercourse initiation among incarcerated Malaysian
adolescents are comparable to those of developed countries. However, in Malaysia,
sexual and reproductive health programmes for such adolescents should be tailored
to address their specific needs.
PMID- 24356757
TI - Changes in the serum cartilage biomarker levels of healthy adults in response to
an uphill walk.
AB - INTRODUCTION: To prevent long-term unfavourable consequences to the articular
cartilage of weight-bearing joints, serum biomarkers can be used to identify
optimum loading of activities. This study aimed to investigate the circulation
pattern of serum cartilage biomarkers in healthy adults in response to an uphill
walk. METHODS: This study recruited 58 healthy participants for the experimental
group and 24 matched participants for the control group. Participants in the
experimental group walked continuously for 14 km on a pathway with a 5.97 degrees
incline, while participants from the control group walked on a horizontal
pathway. Serum was collected from both groups preactivity (i.e. T1), immediately
after activity (i.e. T2) and 24 hours after T1 (i.e. T3). The serum cartilage
oligomeric matrix protein (COMP), chondroitin sulfate-WF6 (WF6) and hyaluronic
acid (HA) levels at each time point were quantified using enzyme-linked
immunosorbent assays, and the results analysed. RESULTS: Both groups shared
similar demographic characteristics and activity duration. At T2, the serum COMP
level of the experimental group was significantly higher than that of the control
group, but the serum HA level of the experimental group was significantly lower
than that of the control group. No significant difference between the serum WF6
levels of the experimental and control groups was observed at T2. CONCLUSION:
Increasing levels of serum COMP demonstrate articular cartilage susceptibility to
the increasing load. An unsustainable, high serum COMP level and an undetectable
change in WF6 level were considered to be a reversible physiological change of
the cartilage. A change in ser um HA level could be related to intensive physical
activity and dynamic clearance rather than a change in cartilage structure.
PMID- 24356758
TI - Vascular endothelial growth factor and insulin-like growth factor-1 in preterm
infants with retinopathy of prematurity.
AB - INTRODUCTION: Retinopathy of prematurity (ROP) can lead to severe visual
impairment. This study was conducted to determine the levels of biochemical
mediators (i. e. vascular endothelial growth f actor [ VEGF] and insulin- like
growth factor-1 [IGF-1]) in the blood of premature infants with proliferative
ROP. METHODS: Blood samples from 71 preterm infants born at or before 32 weeks of
gestation were obtained 6-8 weeks after birth. These infants were classified into
two groups according to their eye examination results. The control group
consisted of 41 infants who had no evidence of ROP, and the study group consisted
of 30 infants with proliferative ROP at stage III or higher. Blood VEGF and IGF-1
levels were measured using enzyme-linked immunosorbent assay. RESULTS: The mean
gestational ages of the infants at birth were 28.4 +/- 1.6 and 28.8 +/- 1.6 weeks
in the study and control groups, respectively (p = 0.259). The mean postmenstrual
age of the infants at the time of blood sampling was 34.9 +/- 1.2 weeks in the
study group and 34.6 +/- 1.3 weeks in the control group (p = 0.339). The mean
blood IGF-1 (18.48 +/- 11.79 ug/L and 16.75 +/- 13.74 ug/L in the study and
control groups, respectively; p = 0.580) and VEGF (267.35 +/- 103.43 pg/mL and
237.52 +/- 130.92 pg/mL in the study and control groups, respectively; p = 0.305)
levels of the infants were not significantly different between the two groups.
CONCLUSION: At 6-8 weeks after birth, blood IGF-1 and VEGF levels were not found
to be significantly different between premature infants with proliferative ROP
and those without.
PMID- 24356759
TI - Comment on: the evolution of sports medicine in Singapore.
PMID- 24356760
TI - Author's reply on comment on the evolution of sports medicine in Singapore.
PMID- 24356761
TI - Comment on: paediatric inflammatory bowel disease in a multiracial Asian country.
PMID- 24356762
TI - Acute unilateral submandibular gland swelling associated with the laryngeal mask
airway.
AB - We describe a rare complication of acute unilateral submandibular gland swelling
following the use of laryngeal mask airway (LMA) in two patients with otherwise
uneventful perioperative airway management. This is likely to be a consequence of
the pressure exerted by the airway cuff on the tissues within the submandibular
triangle. As this complication is rarely reported, its true incidence may in fact
be higher, suggesting a need for greater attention on LMA cuff pressures and
degree of cuff inflation. We discuss the presenting clinical features,
pathophysiology and utilisation of ultrasonographic confirmation of
sialadenopathy, and review the current anaesthetic literature to raise awareness
of this unusual and under-reported complication of LMA. This complication can be
mitigated by incorporating routine manometric checks and limiting intracuff
pressures to < 60 cmH2O, potentially avoiding LMA insertions in patients with
sialolithiasis and avoiding the use of nitrous oxide.
PMID- 24356763
TI - Secondary stent-in-stent self-expanding metallic stent placement for early stent
occlusion due to mucosal oedema in the gastrojejunal anastomosis after palliative
subtotal gastrectomy for locally advanced gastric cancer.
AB - Herein, we report a case of early in-stent occlusion due to the ingrowth of soft
oedematous mucosal tissue through the lattices of an uncovered stent, which was
used for palliation of a postoperative gastrojejunal anastomotic stricture. The
in-stent occulsion was treated with the deployment of a second stent, which was
covered, within the first stent. This led to successful resolution of the
occlusion.
PMID- 24356764
TI - Gastric tuberculosis presenting with a huge abdominal mass.
AB - Tuberculosis of the stomach is extremely rare. We report the case of a 38-year
old woman who presented with epigastric discomfort and a palpable mass that
persisted for a period of one month. We also report our findings from the
abdominal computed tomographic, upper endoscopic and endoscopic ultrasonographic
examinations of the patient. Abdominal computed tomography (CT) showed the
presence of a large mass with an irregularly contoured low attenuation lesion.
Upper endoscopy and endoscopic ultrasonography revealed a protruding ulcerative
mass with an ill-defined heteroechoic subepithelial lesion originating from the
gastric submucosal layer. This was previously misdiagnosed as a gastrointestinal
stromal tumour. Endoscopic biopsy specimen was positive on acid-fast bacillus
staining, and polymerase chain reaction for Mycobacterium tuberculosis was also
positive. Abdominal CT and endoscopy at the patient's three-month follow-up
showed near complete resolution of the lesion.
PMID- 24356765
TI - Lactating breast abscess: a rare presentation of adenosquamous breast carcinoma.
AB - We report the case of a 33-year-old lactating woman who presented with a 10-cm
breast abscess. Biopsy of the abscess wall revealed a poorly differentiated
invasive ductal carcinoma. The patient had no family history of breast cancer or
other risk factors for breast cancer. The disease was considered to be a large
noninflammatory invasive breast cancer, for which the patient received
neoadjuvant chemotherapy, breast-conserving surgery using axillary dissection
(the patient did not consent to a mastectomy), and postoperative radiotherapy.
Final histologic examination revealed a 4-cm, triple negative, high-grade
adenosquamous carcinoma. At follow-up four years after surgery, the patient was
doing well with no signs of recurrence. Adenosquamous carcinoma is an extremely
rare disease that mainly presents in low-grade forms. High-grade forms are
aggressive and frequently present with axillary involvement. To the best of our
knowledge, there has been no report of adenosquamous carcinoma presenting as a
breast abscess in the literature. The case we report highlights that, although
rare, cancer should be considered in lactating breast abscesses.
PMID- 24356766
TI - Anaesthetic management of a patient with Leigh's syndrome with central
hypoventilation and obstructive sleep apnoea.
AB - Leigh's syndrome, which is characterised by progressive neurodegeneration
involving the brainstem and basal ganglia, belongs to a family of disorders
classified as mitochondrial myopathies. It is most commonly transmitted by an
autosomal recessive mode of inheritance, but can sometimes occur in a
mitochondrial pattern. It typically presents during infancy with developmental
delay and deterioration of brainstem function. Respiratory failure is the common
cause of death and postoperative morbidity in patients with Leigh's disease.
Herein, we report the case of a 17-year-old female patient with Leigh's syndrome
who underwent general anaesthesia for a tracheostomy, which was performed in view
of the patient's requirement for long-term ventilation and frequent toileting for
secretions. Her respiratory complications included central hypoventilation
secondary to brainstem involvement, and obstructive sleep apnoea due to obesity
and muscle dystonia. She was hospitalised for acute respiratory decompensation
secondary to hospital-acquired pneumonia. We review the anaesthetic implications
of this disease and discuss its impact on preoperative, intraoperative and
postoperative management.
PMID- 24356767
TI - Enhanced reversible lithium storage in germanium nano-island coated 3D hexagonal
bottle-like Si nanorod arrays.
AB - The rapid development of numerous microscale electronic devices, such as smart
dust, micro or nano bio-sensors, medical implants and so on, has induced an
urgent demand for integratable micro or nano battery supplies with high energy
and power densities. In this work, 3D hexagonal bottle-like Si/Ge composite
nanorod (NR) array electrodes with good uniformity and mechanical stability
potentially used in micro or nano rechargeable Li-ion batteries (LIBs) were
fabricated on Si substrates by a cost-effective, wafer scale and Si-compatible
process. The optimized Ge nano-islands coated Si NR composite arrays as anode
materials exhibit superior areal capacities and cycling performances by virtue of
their favourable structural and improved conductivity features. The unique Si
based composite electrode in nanostructures can be technically and fundamentally
employed to configurate all-solid-state Li-ion micro-batteries as on-chip power
systems integrated into micro-electronic devices such as M/NEMS devices or
autonomous wireless microsystems.
PMID- 24356768
TI - Efficacy of liver parenchymal enhancement and liver volume to standard liver
volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function.
AB - OBJECTIVE: We aimed to develop and assess the efficacy of a liver function index
that combines liver enhancement and liver volume to standard liver volume
(LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd
EOB-DTPA)-enhanced MRI. METHODS: In all, 111 patients underwent a Gd-EOB-DTPA
enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA
administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver
function indices: relative enhancement of the liver, corrected enhancement of the
liver-to-spleen ratio, LSC_N20, increase rate of the liver-to-muscle ratio,
reduction rate of T1 relaxation time of the liver, DeltaR1 of the liver and K
Hep; the indices were multiplied by the LV/SLV ratio. We calculated the
correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA
enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by
using Pearson correlation analysis. RESULTS: There were significant correlations
between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG
clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based
liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P <
0.001) were more strongly correlated with the ICG clearance than those without
multiplication by the LV/SLV ratio. CONCLUSIONS: Gd-EOB-DTPA-enhanced MRI-based
liver function indices that combine liver enhancement and the LV/SLV ratio may
more reliably estimate liver function. KEY POINTS: * Gd-EOB-DTPA-enhanced MRI is
useful for assessing liver function. * Liver enhancement on Gd-EOB-DTPA-enhanced
MRI correlates with indocyanine green (ICG) clearance. * Liver volume to standard
liver volume (LV/SLV) ratio correlates with ICG clearance. * Liver enhancement
and LV/SLV ratio help to estimate liver function.
PMID- 24356769
TI - Obesity does not influence hepcidin and hemojuvelin levels in hemodialysis
patients.
AB - BACKGROUND/AIMS: Clinical studies have shown increased levels of hepcidin causing
functional iron deficiency in obese individuals. This study examined whether
obesity contributes to increased hepcidin and hemojuvelin levels in adult
hemodialysis patients. METHODS: In a case-control design, 37 obese [body mass
index (BMI) >30 kg/m(2)] stable hemodialysis patients and 37 patients with normal
BMI (20-25 kg/m(2)), matched for age, gender and race, who fulfilled a strict set
of inclusion and exclusion criteria were included in the study. Serum hepcidin
and hemojuvelin, markers of iron status and inflammation, and routine
hematological and biochemical variables were measured on samples obtained prior
to the midweek hemodialysis session. RESULTS: Obese and nonobese patients (BMI
35.1 +/- 3.4 vs. 22.8 +/- 1.4 kg/m(2); p < 0.001) were similar with regard to
basic comorbidities and use of erythropoietin and iron. Levels of hemoglobin,
hypochromic red cells and reticulocytes were similar in the two groups. Serum
iron and transferrin saturation levels were on the low side and not different
between obese and lean individuals; total iron-binding capacity showed a trend
towards higher levels in obese patients (48.4 +/- 8.3 vs. 44.9 +/- 7.4 MUmol/l; p
= 0.065). Levels of serum ferritin (651 +/- 302 vs. 705 +/- 327 MUg/l; p = 0.46),
hepcidin (118.3 +/- 67.7 vs. 119.3 +/- 78.0 ng/ml; p = 0.95) and hemojuvelin
(1.90 +/- 1.11 vs. 1.94 +/- 1.24 mg/l; p = 0.90) were high but similar between
the two groups. Serum hepcidin showed a significant correlation only with
ferritin (r = 0.287, p = 0.013). CONCLUSIONS: Hepcidin and hemojuvelin levels are
already considerably elevated in dialysis patients, but obesity does not have an
additional impact. Further studies should examine whether increased weight
contributes towards hepcidin elevation in predialysis individuals, in whom there
is a lesser burden of systemic inflammation.
PMID- 24356770
TI - A plate-based electrochromic approach for the high-throughput detection of
electrochemically active bacteria.
AB - Electrochemically active bacteria (EAB) have the ability to transfer electrons to
electron acceptors located outside the cell, and they are widely present in
diverse environments. In spite of their important roles in geochemical cycles,
environmental remediation and electricity generation, so far, only a limited
number and types of EAB have been isolated and characterized. Thus, effective and
rapid EAB identification methods are highly desirable. In this protocol, we
describe a photometric protocol for the visualization and high-throughput
identification and isolation of EAB. The protocol relies on the fast electron
acquisition and color change ability of an electrochromic material, namely a
tungsten trioxide (WO3) nanorod assembly. The extracellular electron transfer
(EET) from EAB to the WO3 nanorod assembly probe is accompanied by a
bioelectrochromic reaction made evident by the color change of the probe. This
protocol enables researchers to rapidly identify EAB and evaluate their EET
ability either qualitatively with the naked eye or quantitatively by image
analysis. We have also successfully used this protocol to isolate EAB from
environmental samples. The time needed to complete this protocol is ~2 d, with
the actual EAB identification process taking about 5 min.
PMID- 24356771
TI - Lysine-specific chemical cross-linking of protein complexes and identification of
cross-linking sites using LC-MS/MS and the xQuest/xProphet software pipeline.
AB - Chemical cross-linking in combination with LC-MS/MS (XL-MS) is an emerging
technology to obtain low-resolution structural (distance) restraints of proteins
and protein complexes. These restraints can also be used to characterize protein
complexes by integrative modeling of the XL-MS data, either in combination with
other types of structural information or by themselves, to establish spatial
relationships of subunits in protein complexes. Here we present a protocol that
has been successfully used to generate XL-MS data from a multitude of native
proteins and protein complexes. It includes the experimental steps for performing
the cross-linking reaction using disuccinimidyl suberate (a homobifunctional,
lysine-reactive cross-linking reagent), the enrichment of cross-linked peptides
by peptide size-exclusion chromatography (SEC; to remove smaller, non-cross
linked peptides), instructions for tandem MS analysis and the analysis of MS data
via the open-source computational software pipeline xQuest and xProphet
(available from http://proteomics.ethz.ch). Once established, this robust
protocol should take ~4 d to complete, and it is generally applicable to purified
proteins and protein complexes.
PMID- 24356772
TI - Using 5-deoxy-5-[18F]fluororibose to glycosylate peptides for positron emission
tomography.
AB - So far seven peptide-based (18)F-radiopharmaceuticals for diagnostic applications
with positron emission tomography (PET) have entered into clinical trials. Three
candidates out of these seven are glycosylated peptides, which may be explained
by the beneficial influence of glycosylation on in vivo pharmacokinetics of
peptide tracers. This protocol describes the method for labeling peptides with 5
deoxy-5-[(18)F]fluororibose ([(18)F]FDR) as a prosthetic group. The synthesis of
[(18)F]FDR is effected by a nucleophilic fluorination step by using dried
Kryptofix 2.2.2-K2CO3-K(18)F complex and a subsequent HCl-catalyzed hydrolysis.
The conjugation of [(18)F]FDR to the N-terminus aminooxy (-ONH2)-functionalized
peptides is carried out in anilinium buffer at pH 4.6 and at room temperature
(RT, 21-23 degrees C), with the concentration of peptide precursors being 0.3
mM. The procedure takes about 120 min and includes two cartridge isolation steps
and two reversed-phase (RP) HPLC purification steps. The quaternary methyl amine
(QMA) anion exchange cartridge and the hydrophilic-lipophilic balanced (HLB)
cartridge are used for the isolation of (18)F-fluoride and [(18)F]FDR-conjugated
peptides, respectively. The first HPLC purification provides the (18)F
fluorinated precursor of [(18)F]FDR and the second HPLC purification is to
separate labeled peptides from their unlabeled precursors. The final product is
formulated in PBS ready for injection, with a radiochemical purity of >98% and a
radiochemical yield (RCY) of 27-37% starting from the end of bombardment (EOB).
The carbohydrate nature of [(18)F]FDR and the operational convenience of this
protocol should facilitate its general use.
PMID- 24356773
TI - Using Spinach-based sensors for fluorescence imaging of intracellular metabolites
and proteins in living bacteria.
AB - Genetically encoded fluorescent sensors can be valuable tools for studying the
abundance and flux of molecules in living cells. We recently developed a novel
class of sensors composed of RNAs that can be used to detect diverse small
molecules and untagged proteins. These sensors are based on Spinach, an RNA mimic
of GFP, and they have successfully been used to image several metabolites and
proteins in living bacteria. Here we discuss the generation and optimization of
these Spinach-based sensors, which, unlike most currently available genetically
encoded reporters, can be readily generated to any target of interest. We also
provide a detailed protocol for imaging ADP dynamics in living Escherichia coli
after a change from glucose-containing medium to other carbon sources. The entire
procedure typically takes ~4 d including bacteria transformation and image
analysis. The majority of this protocol is applicable to sensing other
metabolites and proteins in living bacteria.
PMID- 24356774
TI - Validation of metal-binding sites in macromolecular structures with the
CheckMyMetal web server.
AB - Metals have vital roles in both the mechanism and architecture of biological
macromolecules. Yet structures of metal-containing macromolecules in which metals
are misidentified and/or suboptimally modeled are abundant in the Protein Data
Bank (PDB). This shows the need for a diagnostic tool to identify and correct
such modeling problems with metal-binding environments. The CheckMyMetal (CMM)
web server (http://csgid.org/csgid/metal_sites/) is a sophisticated, user
friendly web-based method to evaluate metal-binding sites in macromolecular
structures using parameters derived from 7,350 metal-binding sites observed in a
benchmark data set of 2,304 high-resolution crystal structures. The protocol
outlines how the CMM server can be used to detect geometric and other
irregularities in the structures of metal-binding sites, as well as how it can
alert researchers to potential errors in metal assignment. The protocol also
gives practical guidelines for correcting problematic sites by modifying the
metal-binding environment and/or redefining metal identity in the PDB file.
Several examples where this has led to meaningful results are described in the
ANTICIPATED RESULTS section. CMM was designed for a broad audience--biomedical
researchers studying metal-containing proteins and nucleic acids--but it is
equally well suited for structural biologists validating new structures during
modeling or refinement. The CMM server takes the coordinates of a metal
containing macromolecule structure in the PDB format as input and responds within
a few seconds for a typical protein structure with 2-5 metal sites and a few
hundred amino acids.
PMID- 24356775
TI - Spiritual support of cancer patients and the role of the doctor.
AB - PURPOSE: Spiritual care is reported as important for cancer patients, but the
role of the doctor in its provision is unclear. We undertook to understand the
nature of spiritual support for Australian cancer patients and their preferences
regarding spiritual care from doctors. METHODS: Using grounded theory,
semistructured interviews were conducted with 15 cancer patients with advanced
disease in a variety of care settings. Patients were asked about the source of
their spiritual support and how they would like their doctors to engage with them
on spiritual issues. RESULTS: Three themes were identified as follows: (1)
sources of spiritual support which helped patients cope with illness and meet
spiritual needs, (2) facilitators of spiritual support, and (3) role of the
doctor in spiritual support. Regardless of religious background, the majority of
patients wanted their doctor to ask about their source of spiritual support and
facilitate access to it. Patients did not want spiritual guidance from their
doctors, but wanted to be treated holistically and to have a good relationship,
which allowed them to discuss their fears. Doctors' understanding of the
spiritual dimension of the patient was part of this. CONCLUSIONS: Spirituality is
a universal phenomenon. Patients in a secular society want their doctor to take
an interest in their spiritual support and facilitate access to it during
illness.
PMID- 24356776
TI - Cannula dacryocystorhinostomy: a simple, innovative and cost-effective method of
lacrimal surgery.
AB - To compare our innovative, cost-effective method of lacrimal surgery with other
methods. A prospective cohort study. The study included 80 eyes of 80 consecutive
patients who presented to our clinic between January 2009 and December 2011. The
patients underwent surgery using a new technique with a specially designed
cannula and were followed according to our protocol. Patency on irrigation. Of
the 80 cases enrolled, the procedure was successful in 52.5 % with a mean follow
up of 247.2 days. The success rate was significantly affected by the preoperative
conditions (p = 0.001) and follow-up duration (p = 0.006). This simple innovative
technique was cost-effective and the results were comparable with those of other
techniques.
PMID- 24356777
TI - Where to build it?
PMID- 24356778
TI - Passive smoking exposure is associated with increased risk of COPD in never
smokers.
AB - BACKGROUND: Passive smoking, or environmental tobacco smoke (ETS), is a risk
factor for lung cancer, cardiovascular disease, and childhood asthma, but a
relationship with COPD has not been fully established. Our aim was to study ETS
as a risk factor for COPD in never smokers. METHODS: Data from three cross
sectional studies within the Obstructive Lung Disease in Northern Sweden (OLIN)
database were pooled. Of the 2,182 lifelong never smokers, 2,118 completed
structured interviews and spirometry of acceptable quality. COPD was defined
according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease)
criteria using postbronchodilator spirometry. The association of COPD with ETS in
single and multiple settings was calculated by multivariate logistic regression
adjusting for known risk factors for COPD. RESULTS: COPD prevalence was
associated with increased ETS exposure: 4.2% (no ETS), 8.0% (ETS ever at home),
8.3% (ETS at previous work), and 14.7% (ETS ever at home and at both previous and
current work), test for trend P = .003. Exclusion of subjects aged >= 65 years
and subjects reporting asthma yielded similar results. ETS in multiple settings,
such as ever at home and at both previous and current work, was strongly
associated to COPD (OR, 3.80; 95% CI, 1.29-11.2). CONCLUSIONS: In this population
based sample of never smokers, ETS was independently associated with COPD. The
association was stronger for ETS in multiple settings. ETS in multiple settings
was, after age, the strongest risk factor for COPD and comparable to personal
smoking of up to 14 cigarettes/d in comparable materials. The findings strongly
advocate measures against smoking in public places.
PMID- 24356779
TI - Violent behavior and driving under the influence of alcohol: prevalence and
association with impulsivity among individuals in treatment for alcohol
dependence in Poland.
AB - BACKGROUND: Driving while intoxicated or under the influence (DUI; for the
purposes of this paper, we use the following terms synonymously: driving under
the influence, driving while intoxicated, and drunk driving) and engaging in
interpersonal violence are two injury-related problems of high public health
importance that have both been linked to alcohol consumption. This study sought
to estimate the prevalence of DUI and violence in a sample of individuals in
treatment for alcohol dependence in Poland. Patient characteristics associated
with DUI and violence involvement, with a particular focus on impulsivity, were
examined. METHODS: Three hundred and sixty-four patients consecutively admitted
to four alcohol treatment programs in Warsaw, Poland participated in this study.
Questions concerning history of interpersonal violence as well as those about DUI
were derived from the Michigan Alcoholism Screening Test. Impulsivity level was
measured using the Barratt Impulsiveness Scale 11, the Revised NEO Personality
Inventory, and the stop-signal task. RESULTS: Among all participants in the
study, 148 (40.1%) had been arrested in the past for DUI, and 196 (55%) reported
involvement in a fight under the influence of alcohol (FUI). The DUI group had a
significantly earlier onset of alcohol problems, a longer period of heavy alcohol
use, and fewer women in comparison to participants without a DUI history. FUI
patients were significantly younger, with a younger average age of onset of
drinking problems, longer period of heavy drinking, and lower percentage of women
than the non-FUI group. CONCLUSION: Both of the self-reported measures of
impulsivity indicated a higher level of impulsivity among participants from the
FUI group than those from the non-FUI group.
PMID- 24356780
TI - Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with
activated Wnt signaling: further evidence for the existence of a tumor stem cell
niche?
AB - INTRODUCTION: Early disease onset, clinical manifestation, histomorphology, and
increased tendency to relapse distinguish the adamantinomatous craniopharyngioma
(adaCP) from the more favorable papillary variant (papCP). A molecular hallmark
of adaCP is the activated Wnt signaling pathway indicated by nuclear beta-catenin
accumulation in a subset of tumor cells. A mouse model recently illustrated that
these cells are the driving force in tumorigenesis of adaCP. This observation and
the peculiar growth pattern points to the existence of a specific tumor stem cell
(TSC) population in human CP. MATERIALS AND METHODS: To prove this hypothesis,
the TSC markers CD133 (Prominin1) and CD44 were examined in papCP (n = 8) and
adaCP (n = 25) on mRNA level using quantitative real time PCR of total tumor RNA.
Furthermore, we investigated protein expression performing immunohistochemical
analyses of formalin-fixed paraffin embedded tumor samples. RESULTS: PapCP
revealed a homogenous CD44 expression pattern predominantly at the cell membrane,
whereas CD133 labeling was hardly detectable. In adaCP, on the other hand all
markers were consistently and predominantly co-expressed in nuclear beta-catenin
accumulating cell clusters, which was confirmed by double immunofluorescence
staining. Overall expression of CD44 was significantly decreased in adaCP versus
papCP, whereas CD133 showed significantly higher protein and mRNA levels in
adaCP. CONCLUSIONS: Our results indicate tumor stem cell-like characteristics of
beta-catenin accumulating cell clusters in adaCP, which may represent a tumor
stem cell niche and might contribute to tumor recurrence. The potential impact of
these special cell groups in regard to future CP management, including
postoperative follow-up and additional treatment remains to be explored.
PMID- 24356781
TI - Evaluation of hypothalamic-pituitary function in children following acute
bacterial meningitis.
AB - BACKGROUND: Previous studies in adults and case reports in children have shown
increased frequency of hypothalamo-pituitary dysfunction after infectious
diseases of the central nervous system. The aim of this study was to evaluate the
function of hypothalamo-pituitary axis in children with a history of bacterial
meningitis. METHODS: Patients diagnosed with bacterial meningitis between April
2000 and June 2011 was included. Baseline and stimulated hormonal tests were
performed as required for hormonal evaluations following a diagnosis of
meningitis. RESULTS: Pituitary function was assessed following a period of 8-135
months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male,
15 pubertal) with mean age of 11.1 +/- 4.4 years were included. Mean height SDS
was 0.01 +/- 1.07 and mean BMI SDS was 0.54 +/- 1.15 all patients had a SDS above
-2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal
functions in all patients. Gonadotropin deficiency was not detected in any of the
pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD)
according to age, sex and Tanner stage, but peak GH response in clonidin test was
>10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these
cases. The fourth case has died before the test. No one had TSH deficiency and
diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our
findings suggest that hypothalamo-pituitary dysfunction is not as common in
childhood as in adulthood. The most remarkable finding was neurosecretary
dysfunction of GH in some cases.
PMID- 24356782
TI - Morphological and inflammatory changes in visceral adipose tissue during obesity.
AB - Obesity is a major health burden worldwide and is a major factor in the
development of insulin resistance and metabolic complications such as type II
diabetes. Chronic nutrient excess leads to visceral adipose tissue (VAT)
expansion and dysfunction in an active process that involves the adipocytes,
their supporting matrix, and immune cell infiltrates. These changes contribute to
adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death.
Accumulation of lymphocytes, macrophages, and other immune cells around dying
adipocytes forms the so-called "crown-like structure", a histological hallmark of
VAT in obesity. Cross talk between immune cells in adipose tissue dictates the
overall inflammatory response, ultimately leading to the production of pro
inflammatory mediators which directly induce insulin resistance in VAT. In this
review, we summarize recent studies demonstrating the dramatic changes that occur
in visceral adipose tissue during obesity leading to low-grade chronic
inflammation and metabolic disease.
PMID- 24356783
TI - Papillary thyroid carcinoma with predominant spindle cell component: report of
two rare cases and discussion on the differential diagnosis with other spindled
thyroid neoplasm.
AB - Spindle cell transformation or metaplasia has been so far demonstrated in the
context of both benign and malignant conditions. Spindle cell lesions of the
thyroid gland of either primary or secondary origin to metastatic disease
represent rare entities. We describe two patients with papillary thyroid
carcinoma (PTC) showing spindle cell metaplasia, submitted to thyroidectomy due
to euthyroid bilateral nodular thyroid disease. Cytological examination of fine
needle aspiration biopsy performed in the dominant nodules was consistent with
follicular neoplasm in one case and with a hyperplastic/adenomatous nodule in the
other patient. Histological examination disclosed unencapsulated follicular
variant of PTC with spindle cell metaplasia in either cases. Both patients are
doing well without clinical or laboratory evidence of PTC recurrence at 3- and 1
year follow-up, respectively. We present the clinical, pathological, and
immunohistochemical aspects of these unusual cases and thoroughly discuss the
differential diagnosis with other spindle cell lesions of the thyroid gland.
PMID- 24356784
TI - Treatment of movement disorder emergencies.
AB - Movement disorder emergencies are defined as clinical scenarios where a movement
disorder develops over hours to days, and in which morbidity and even mortality
can result from failure to appropriately diagnose and manage the patient. The
last decade has seen increasing recognition of various movement disorder
emergencies, including acute parkinsonism, neuroleptic malignant syndrome,
respiratory compromise in multiple system atrophy, dystonic storm, oculogyric
crisis, and hemiballism, among others. This article will review the major
movement disorder emergencies encountered in the hospital and office, emphasizing
practical management and treatment.
PMID- 24356786
TI - Ample active acoustic space of a frog from the South American temperate forest.
AB - The efficiency of acoustic communication depends on the power generated by the
sound source, the attributes of the environment across which signals propagate,
the environmental noise and the sensitivity of the intended receivers. Eupsophus
emiliopugini, an anuran from the temperate austral forest communicates by means
of an advertisement call of moderate intensity within the range for anurans. To
estimate the range over which these frogs communicate effectively, we conducted
measurements of call sound levels and of auditory thresholds to pure tones and to
synthetic conspecific calls. The results show that E. emiliopugini produces
advertisement calls of about 84 dB SPL at 0.25 m from the caller. The signals are
affected by attenuation as they propagate, reaching average values of about 47 dB
SPL at 8 m from the sound source. Midbrain multi-unit recordings show quite
sensitive audiograms within the anuran range, with thresholds of about 44 dB SPL
for synthetic imitations of conspecific calls, which would allow communication at
distances beyond 8 m. This is an extended range as compared to E. calcaratus, a
related syntopic species for which a previous study has shown to be restricted to
active acoustic spaces shorter than 2 m. The comparison reveals divergent
strategies for related taxa communicating amid the same environment.
PMID- 24356785
TI - Treatment of functional (psychogenic) movement disorders.
AB - Functional (psychogenic) movement disorders are a common source of disability and
distress. Despite this, little systematic evidence is available to guide
treatment decisions. This situation is likely to have been influenced by the "no
man's land" that such patients occupy between neurologists and psychiatrists,
often with neither side feeling a clear responsibility or ability to direct
management. The aim of this narrative review is to provide an overview of the
current state of the evidence regarding management of functional movement
disorders. This reveals that there is some evidence to support the use of
specific forms of cognitive behavioral therapy and physiotherapy. Such treatments
may be facilitated in selected patients with the use of antidepressant
medication, and may be more effective for those with severe symptoms when given
as part of inpatient multidisciplinary rehabilitation. Other treatments, for
example hypnosis and transcranial magnetic stimulation, are of interest, but
further evidence is required regarding mechanism of effect and long-term benefit.
Though prognosis is poor in general, improvement in symptoms is possible in
patients with functional movement disorders, and there is a clear challenge to
clinicians and therapists involved in their care to conduct and advocate for high
quality clinical trials.
PMID- 24356788
TI - Hollow/porous nanostructures derived from nanoscale metal-organic frameworks
towards high performance anodes for lithium-ion batteries.
AB - Lithium-ion batteries (LIBs), owing to their high energy density, light weight,
and long cycle life, have shown considerable promise for storage devices. The
successful utilization of LIBs depends strongly on the preparation of
nanomaterials with outstanding lithium storage properties. Recent progress has
demonstrated that hollow/porous nanostructured oxides are very attractive
candidates for LIBs anodes due to their high storage capacities. Here, we aim to
provide an overview of nanoscale metal-organic frameworks (NMOFs)-templated
synthesis of hollow/porous nanostructured oxides and their LIBs applications. By
choosing some typical NMOFs as examples, we present a comprehensive summary of
synthetic procedures for nanostructured oxides, such as binary, ternary and
composite oxides. Hollow/porous structures are readily obtained due to volume
loss and release of internally generated gas molecules during the calcination of
NMOFs in air. Interestingly, the NMOFs-derived hollow/porous structures possess
several special features: pores generated from gas molecules release will connect
to each other, which are distinct from "dead pores"; pore size often appears to
be <10 nm; in terms of surface chemistry, the pore surface is hydrophobic. These
structural features are believed to be the most critical factors that determine
LIBs' performance. Indeed, it has been shown that these NMOFs-derived
hollow/porous oxides exhibit excellent electrochemical performance as anode
materials for LIBs, including high storage capacity, good cycle stability, and so
on. For example, a high charge capacity of 1465 mA h g(-1) at a rate of 300 mA g(
1) was observed after 50 cycles for NMOFs-derived Co3O4 porous nanocages, which
corresponds to 94.09% of the initial capacity (1557 mA h g(-1)), indicating
excellent stability. The capacity of NMOFs-derived Co3O4 is higher than that of
other Co3O4 nanostructures obtained by a conventional two-step route, including
nanosheets (1450 mA h g(-1) at 50 mA g(-1)), nanobelts (1400 mA h g(-1) at 40 mA
g(-1)) and nanoflowers (694 mA h g(-1) at 100 mA g(-1)). The capacity is also
better than Co3O4 octahedra obtained by a one-step hydrothermal method (946 mA h
g(-1) at 100 mA g(-1)). In this review, we will summarize the recent research
advances on NMOFs-derived hollow/porous oxides as LIBs anodes. The enhanced
lithium storage properties have been discussed in relation to their special
structural parameters. Moreover, remarks on the current challenges and
perspectives for future NMOFs applications are proposed. Through this systematic
review, we aim to stress the importance of NMOFs templates for the fabrication of
hollow/porous functional materials that would result in improved physicochemical
properties and provide insights to guide future research for LIBs applications.
PMID- 24356787
TI - Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus
influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster
dose and 2-dose catch-up regimens in the second year of life.
AB - In a previous study, 3-dose primary vaccination of Nigerian infants with the 10
valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate
vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with
comparable tolerability between PHiD-CV and control groups. In an open-label
study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV
booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa)
booster dose at 15-21 months and 36 children unprimed for pneumococcal
vaccination received two PHiD-CV catch-up doses (first dose co-administered with
DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and
immune responses were measured before and one month after vaccination. In both
groups, pain was the most frequent solicited local symptom and fever was the most
frequent solicited general symptom after the booster dose and each catch-up dose.
Few grade 3 solicited symptoms and no vaccine-related serious adverse events were
reported. After booster vaccination, for each vaccine serotype, at least 98.5% of
children had an antibody concentration >= 0.2 ug/ml and at least 94.0% had an
opsonophagocytic activity (OPA) titer >= 8. After 2-dose catch-up, for each
vaccine serotype, at least 97.1% had an antibody concentration >= 0.2 ug/ml,
except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA
titer >=8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced
antibody responses against protein D in both groups. In conclusion, PHiD-CV
administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well
tolerated and immunogenic for vaccine pneumococcal serotypes and protein D.
PMID- 24356789
TI - Background concentrations of heavy metals in benthos from transboundary rivers of
the Transbaikalia region, Russia.
AB - The concentrations (mg/kg dry weight) of Cu, Zn, As, Cd, Hg, and Pb were measured
in benthic macroalgae and invertebrates collected in the upper transboundary
tributaries of the Onon River, Transbaikalia, Russia. The background
concentration ranges in Cladophora fracta, Ulothrix zonata and Zygnemataceae
were: 6.4-9.1 for Cu, 27.2-73.1 for Zn, 0.4-0.9 for Cd, 6.7-35.3 for As, 0.01
0.02 for Hg, and 1.9-4.3 for Pb. In Brachycentrus americanus and Lymnaea media
the concentration ranges were: 9.0-25.5 for Cu, 21.4-96.0 for Zn, 0.1-0.3 for Cd,
1.7-5.6 for As, 0.004-0.02 for Hg, and 0.4-2.2 for Pb. The concentrations of Cu,
Zn, Pb, and Hg were consistent with data for uncontaminated areas. Under
contamination conditions the concentrations in C. fracta were: 938 for Zn, 513
for Pb, and 9.5 for Cd; in Lymnaea media were: 46.8 for Cu, 176 for Zn, 52.3 for
Pb, and 3.0 for Cd. All the organisms showed a common response to contamination,
and consequently can be used as biomonitors of contamination by heavy metals.
PMID- 24356790
TI - Quasi-one-dimensional electronic states induced by an extended line defect in
graphene: an analytic solution.
AB - Analytic solutions of the quasi-one-dimensional (q1D) electron states around an
extended line defect in a graphene lattice are derived within the tight-binding
model. Then, the electronic properties of this kind of boundary state in graphene
are studied in detail. It is found that one subband composed of the even-parity
boundary states emerges in the vicinity of the Dirac point. In particular, when
the bulk band is gapped, such a one-dimensional subband remains in the bandgap,
spanning two inequivalent valleys. In addition, this boundary state subband
exhibits nontrivial dispersion, which can carry the valley polarized charge
current flowing along the extended line defect. As a result, the line defect
behaves like a one-dimensional channel for electronic transport. Moreover, its
appearance in graphene or a hexagonal boron nitride sheet provides a promising
way to print electric circuits in these two-dimensional materials.
PMID- 24356791
TI - Encapsulation status of papillary thyroid microcarcinomas is associated with the
risk of lymph node metastases and tumor multifocality.
AB - The management of papillary microcarcinoma (PMC) of the thyroid is controversial,
especially after partial thyroid resection for benign thyroid disease. In order
to detect prognostic factors for PMC, we analyzed 116 patients with PMC for
encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116
patients with PMC have been operated in our department (87 females, 29 males,
median age 49 years). Eighty per cent of PMCs were diagnosed postoperatively.
Seventy-six patients (66%) received a more extended resection with either
thyroidectomy, near total thyroidectomy, or Dunhill operation either primarily or
after completion operation, whereas 40 patients (34%) had only partial resection.
Fifty patients (43%) received radioiodine (RIA) ablation. Lymph node metastases
were found in 21 patients (18%). Univariate analysis showed four risk factors to
be significantly associated with the risk of lymph node metastasis (p<0.05): male
gender, younger age, age group<50 years and nonencapsulation of the tumor.
Multivariate analysis demonstrated statistical significance for gender and tumor
capsulation status. The tumor capsulation status also correlated with tumor
multifocality. Our data show that the risk of lymph node metastases is
significantly higher in partially or nonencapsulated PMC than in encapsulated
specimens. We therefore suggest that the WHO classification should be extended to
a compulsory notification of the encapsulation status in PMC.
PMID- 24356792
TI - The glucose and lipid effects of colesevelam as monotherapy in drug-naive type 2
diabetes.
AB - Colesevelam has shown efficacy in adults with type 2 diabetes mellitus (T2DM) in
combination with metformin-, sulfonylurea-, or insulin-based therapy, lowering
hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol levels. A study
was conducted to evaluate colesevelam as monotherapy in drug-naive patients with
T2DM. In this randomized, double-blind, placebo-controlled, parallel-group study,
adults with T2DM who had inadequate glycemic control (HbA1c >=7.5% and <=9.5%)
with diet and exercise alone were randomized to receive colesevelam 3.75 g/day
(n=176) or placebo (n=181) for 24 weeks. The primary efficacy variable was HbA1c
at week 24. Colesevelam as compared to placebo showed significant reductions from
baseline in HbA1c (-2.92 mmol/mol [0.3%]; p=0.01) and fasting plasma glucose (
10.3 mg/dl; p=0.04) at week 24 with last observation carried forward. Colesevelam
also significantly reduced low-density lipoprotein cholesterol (-11.2%;
p<0.0001), total cholesterol (-5.1%; p=0.0005), non-high-density lipoprotein
cholesterol (-7.4%; p=0.0001), and apolipoprotein B (-6.5%; p=0.0001) and
increased apolipoprotein A-I (+ 2.4%; p=0.04), and triglycerides (+ 9.7%;
p=0.03). Colesevelam monotherapy resulted in statistically significant
improvements in glycemic and most lipid parameters in subjects with type 2
diabetes, with no new or unexpected safety and tolerability issues. Modest
reductions in HbA1c and low-density lipoprotein cholesterol levels with
colesevelam further support its use in combination with other antidiabetes agents
when treatment targets for these parameters are close but are not quite
achieved.ClinicalTrials.gov identifier: NCT00789737.
PMID- 24356793
TI - Mouse plasma progesterone levels are affected by different dietary omega6/omega3
ratios.
AB - An imbalance in the dietary polyunsaturated fatty acids (PUFAs) omega6/omega3
ratio, could influence negatively the reproductive performance. The aim of the
study was to assess the effects of chronic administration of diets enriched with
soybean or sunflower oils with different omega6/omega3 ratios on the reproductive
parameters of adult female mice. Mice were fed different diets for 90 days: a
commercial diet (CD), a 5 or 10% soy oil-enriched diet (SOD5 and SOD10,
respectively), and a 5 or 10% sunflower oil-enriched diet (SFOD5 and SFOD10,
respectively). The parameters evaluated were: body weight and food intake,
estrous cycle, plasma progesterone concentration, ovulation rate, and oocyte
quality. Progesterone concentrations (ng/ml) were significantly higher in the
SFOD10: 14.9+/-2.8 vs CD: 5.4+/-1.2; SOD5: 5.6+/-1.1 and SFOD5: 4.6+/-1.4.
Additional parameters evaluated were not affected. However, metestrous and luteal
phases were shorter in subjects receiving SOD and longer in those under SFOD
diets. In SFOD, there was a trend towards a smaller number of recruited oocytes
compared to CD and SOD and a higher percentage of cleaved oocytes were quantified
in SOD diets. A 3-month supply of a diet with elevated LA omega6/ALA omega3 ratio
to adult female mice affects their reproductive physiology, modifying
progesterone production, ovulation rate, and/or oocyte quality. Although some
differences in the response to diets have been observed in several mammalian
species, the present findings must be taken into consideration when a diet for
optimizing reproductive capability is indicated.
PMID- 24356794
TI - Novel mutation p.A64D in the Serpina7 gene as a cause of partial thyroxine
binding globulin deficiency associated with increases affinity in transthyretin
by a known p.A109T mutation in the TTR gene.
AB - Partial thyroxine-binding globulin deficiency (TBG-PD) is an endocrine defect
with a prevalence of 1:4 000 in newborns. Due to the presence of a single TBG
gene on the X chromosome, most familial TBG defects follow an X-linked
inheritance pattern. Abnormal T4 binding to T4-binding prealbumin (TTR) is a rare
cause of euthyroid hyperthyroxinemia, which is transmitted by autosomal dominant
inheritance. The purpose of the present study was to identify and characterize
new mutations in the Serpina7 and TTR genes in a complete family with typical TBG
PD. All patients underwent clinical and biochemical evaluation. Sequencing of
DNA, population screening by (SSCP) analysis, and bioinformatics studies were
performed. Molecular studies revealed a novel p.A64D mutation in the exon 1 of
Serpina7 gene associated with the previously reported p.A109T mutation in the
exon 4 of TTR gene. To our knowledge, this is the first report of a patient with
a TBG-PD by a mutation in Serpina7 that was coincident with a mutation in TTR
gene that increased affinity of TTR for T4. This work contributes to elucidate
the molecular basis of the defects of thyroid hormone transport in serum and the
improvement of the diagnosis avoiding unnecessary therapy.
PMID- 24356795
TI - Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and
leptin in subjects with type 2 diabetes mellitus.
AB - Recent evidence suggests that omega-3 polyunsaturated fatty acids [n-3 PUFAs:
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], improve insulin
sensitivity in humans. In a double-blind, placebo-controlled, randomized,
crossover study, we investigated the effects of EPA/DHA on paraoxonase-1 activity
as well as fasting and postprandial levels of circulating adiponectin and leptin
in 34 subjects with type 2 diabetes mellitus who received daily for 6 weeks
either 2 g purified EPA/DHA or olive oil (placebo), separated by a 6 weeks
washout. At the end of each treatment, measurements were performed in fasting
state and 2, 4, and 6 h following a standardized high-fat meal (600 kcal). No
significant differences in fasting and postprandial circulating adiponectin,
leptin, and paraoxonase-1 activity were seen between n-3 PUFAs and placebo. Our
data do not support an insulin sensitizing effect of n-3 PUFAs by means of
influencing circulating adipocytokines in this population. Clinical Trial
Register Number: NCT00328536.
PMID- 24356796
TI - Selectivity and specificity of small molecule fluorescent dyes/probes used for
the detection of Zn2+ and Ca2+ in cells.
AB - Fluorescent dyes are widely used in the detection of labile (free or
exchangeable) Zn(2+) and Ca(2+) in living cells. However, their specificity over
other cations and selectivity for detection of labile vs. protein-bound metal in
cells remains unclear. We characterized these important properties for commonly
used Zn(2+) and Ca(2+) dyes in a cellular environment. By tracing the
fluorescence emission signal along with UV-Vis and size exclusion chromatography
inductively coupled plasma mass spectrometry (SEC-ICP-MS) in tandem, we
demonstrated that among the dyes used for Zn(2+), Zinpyr-1 fluoresces in the low
molecular mass (LMM) region containing labile Zn(2+), but also fluoresces in
different molecular mass regions where zinc ion is detected. However, FluoZinTM-3
AM, Newport GreenTM DCF and Zinquin ethyl ester display weak fluorescence, lack
of metal specificity and respond strongly in the high molecular mass (HMM)
region. Four Ca(2+) dyes were studied in an unperturbed cellular environment, and
two of these were tested for binding behavior under an intracellular Ca(2+)
release stimulus. A majority of Ca(2+) was in the labile form as tested by SEC
ICP-MS, but the fluorescence from Calcium Green-1TM AM, Oregon Green(r) 488 BAPTA
1, Fura redTM AM and Fluo-4 NW dyes in cells did not correspond to free Ca(2+)
detection. Instead, the dyes showed non-specific fluorescence in the mid- and
high-molecular mass regions containing Zn, Fe and Cu. Proteomic analysis of one
of the commonly seen fluorescing regions showed the possibility for some dyes to
recognize Zn and Cu bound to metallothionein 2. These studies indicate that
Zn(2+) and Ca(2+) binding dyes manifest fluorescence responses that are not
unique to recognition of labile metals and bind other metals, leading to
suboptimal specificity and selectivity.
PMID- 24356797
TI - Positive and negative family emotional climate differentially predict youth
anxiety and depression via distinct affective pathways.
AB - A socioaffective specificity model was tested in which positive and negative
affect differentially mediated relations of family emotional climate to youth
internalizing symptoms. Participants were 134 7(th)-9(th) grade adolescents (65
girls; 86 % Caucasian) and mothers who completed measures of emotion-related
family processes, experienced affect, anxiety, and depression. Results suggested
that a family environment characterized by maternal psychological control and
family negative emotion expressiveness predicted greater anxiety and depression,
and was mediated by experienced negative affect. Conversely, a family emotional
environment characterized by low maternal warmth and low positive emotion
expressiveness predicted only depression, and was mediated through lowered
experienced positive affect. This study synthesizes a theoretical model of
typical family emotion socialization with an extant affect-based model of shared
and unique aspects of anxiety and depression symptom expression.
PMID- 24356798
TI - Comparison of sentinel lymph node biopsy guided by the multimodal method of
indocyanine green fluorescence, radioisotope, and blue dye versus the
radioisotope method in breast cancer: a randomized controlled trial.
AB - PURPOSE: This study aimed to evaluate the identification rate and surgery time of
sentinel lymph node biopsy (SLNB) by a multimodal method (MMM) using a mixture of
indocyanine green (ICG), radioisotope (RI), and blue dye (BD) compared with the
RI alone. METHODS: In this phase II randomized study, 86 patients with clinically
node-negative breast cancer were enrolled and received SLNB with either MMM or
RI. We compared the identification rate, number of sentinel lymph nodes (SLNs),
and detection time of SLNB and evaluated the safety. RESULTS: The mean age of the
MMM group and RI group was 48.2 and 51.0 years (p = 0.12), respectively. There
were no differences in histopathologic factors, including tumor size, node
positivity, and hormone receptor positivity between groups. SLNs were identified
in all patients of both groups (100 % in the MMM group and 100 % in the RI
group). The average number of SLNs in the MMM group was more than that in the RI
group (3.4 +/- 1.37 vs. 2.3 +/- 1.04, respectively; p < 0.001). The time to
detect the first sentinel lymph node was similar in each group (6.5 +/- 5.16 vs.
8.0 +/- 4.35 min; p = 0.13). In the MMM group, percutaneous lymphatic drainage
was visualized by fluorescent imaging in 90.7 % (39 of 43 patients). During and
after the operation, there were no complications, including allergic reactions,
skin staining, or necrosis. CONCLUSIONS: This study is the first randomized trial
that compared MMM using ICG, RI, and BD and the conventional RI method for SLNB.
MMM is a feasible and safe method for SLNB.
PMID- 24356799
TI - Outcome data of patients with peritoneal carcinomatosis from gastric origin
treated by a strategy of bidirectional chemotherapy prior to cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy in a single specialized
center in Japan.
AB - BACKGROUND: Management of peritoneal disseminated gastric cancer (GC) remains a
challenging problem. The purpose of our study was to evaluate the outcome of
bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic
induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC)
arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic
intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Overall, 194 patients
with PC arising from GC were treated with BIPSC comprising intraperitoneal
docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed
by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed
in responders to BIPSC. RESULTS: Of these 194 patients, 152 (78.3 %) underwent
CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality
was 3.9 %, and major complications occurred in 23.6 % of patients. The median
survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32
and 10.7 %, respectively, in the patients treated with combined treatment.
Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low
tumor burden [peritoneal cancer index (PCI) <= 6] (p = 0.001), and completeness
of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis.
CONCLUSION: As a viable option, BIPSC with CRS and HIPEC for patients with PC
arising from GC may be performed safely, with acceptable morbidity and mortality,
in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal
dissemination seem to be essential to achieve the best outcomes in these
patients.
PMID- 24356800
TI - Molecular imaging of tumor-associated angiogenesis using a novel magnetic
resonance imaging contrast agent targeting alphavbeta 3 integrin.
AB - BACKGROUND: The recent introduction of biological anticancer therapy has renewed
the interest in functional imaging of tumor-associated angiogenesis (TAA) as a
tool to monitor early therapy response. The present study evaluated imaging of
TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe
targeting alphavbeta3 integrin. METHODS: HT29 human colorectal cancers were grown
in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE
sequence up to 110 min after injection of P1227 or gadolinium
tetraazacyclododecane tetraacetic acid (Gd-DOTA). Specificity was assessed by
using P1227 1 h after intravenous administration of the alphavbeta3 inhibitor
cilengitide. Regions of interest were drawn encompassing the tumor rim and normal
muscle. Imaging data were compared with microvessel density and alphavbeta3
expression. RESULTS: Using P1227, specific enhancement of the angiogenic tumor
rim, but not of normal muscle, was observed, whereas Gd-DOTA enhanced tumor and
normal muscle. After administering cilengitide, enhancement with P1227, but not
with DOTA, was significantly suppressed during the first 20 min. When using
P1227, a significant correlation was observed between normalized enhancement of
the tumor rim and immunohistochemical alphavbeta3 integrin expression.
CONCLUSIONS: Molecular MRI using a small monogadolinated tracer targeting
alphavbeta3 integrin and moderate magnetic field strength holds promise in
assessing colorectal TAA.
PMID- 24356801
TI - Perceived usability and use of custom-made footwear in diabetic patients at high
risk for foot ulceration.
AB - OBJECTIVE: To assess the perceived usability and use of custom- made footwear in
diabetic patients who are at high-risk for foot ulceration, and to elucidate the
determinants of usability and use. DESIGN: Survey. SUBJECTS: A total of 153
patients with diabetes, peripheral neuropathy, prior plantar foot ulceration and
newly prescribed custom-made footwear, recruited from 10 Dutch multidisciplinary
foot clinics. METHODS: The Questionnaire of Usability Evaluation was used to
assess the patients' perception of weight, appearance, comfort, durability,
donning/doffing, stability, benefit and overall appreciation of their
prescription footwear (all expressed as visual analogue scores). Data on
priorities for usability and footwear use (in h/day) were obtained from patient
reports. Multivariate logistic regression analysis was used to assess
determinants of usability and use. RESULTS: Median (interquartile range) score
for overall appreciation was 8.3 (7.1-9.1). Scores ranged from 6.5 (4.5-8.6) for
weight to 9.6 (6.3-9.9) for donning/doffing. Footwear comfort was listed most
often (33.3%) as the highest priority. Footwear use was <60% of daytime (where
daytime was defined as 16 h out of bed) in 58% of patients. The only significant
determinant of footwear use was the perceived benefit of the footwear (p =
0.045). CONCLUSION: Perceived usability of footwear was mostly positive, although
individual scores and priorities varied considerably. Footwear use was low to
moderate and dependent only on the perceived benefit of the footwear. Therefore,
practitioners should focus on enhancing the patient's ap-preciation of the
therapeutic benefit of custom-made footwear.
PMID- 24356802
TI - Does applying technology throughout the medication use process improve patient
safety with antineoplastics?
AB - PURPOSE: Medical errors, in particular medication errors, continue to be a
troublesome factor in the delivery of safe and effective patient care.
Antineoplastic agents represent a group of medications highly susceptible to
medication errors due to their complex regimens and narrow therapeutic indices.
As the majority of these medication errors are frequently associated with
breakdowns in poorly defined systems, developing technologies and evolving
workflows seem to be a logical approach to provide added safeguards against
medication errors. SUMMARY: This article will review both the pros and cons of
today's technologies and their ability to simplify the medication use process,
reduce medication errors, improve documentation, improve healthcare costs and
increase provider efficiency as relates to the use of antineoplastic therapy
throughout the medication use process. Several technologies, mainly computerized
provider order entry (CPOE), barcode medication administration (BCMA), smart
pumps, electronic medication administration record (eMAR), and telepharmacy, have
been well described and proven to reduce medication errors, improve adherence to
quality metrics, and/or improve healthcare costs in a broad scope of patients.
The utilization of these technologies during antineoplastic therapy is weak at
best and lacking for most. Specific to the antineoplastic medication use system,
the only technology with data to adequately support a claim of reduced medication
errors is CPOE. In addition to the benefits these technologies can provide, it is
also important to recognize their potential to induce new types of errors and
inefficiencies which can negatively impact patient care. CONCLUSION: The
utilization of technology reduces but does not eliminate the potential for error.
The evidence base to support technology in preventing medication errors is
limited in general but even more deficient in the realm of antineoplastic
therapy. Though CPOE has the best evidence to support its use in the
antineoplastic population, benefit from many other technologies may have to be
inferred based on data from other patient populations. As health systems begin to
widely adopt and implement new technologies it is important to critically assess
their effectiveness in improving patient safety.
PMID- 24356803
TI - Dosing of carboplatin in a patient with amputated legs: A case report.
AB - Carboplatin is a platinum derivative that is commonly used in combination
chemotherapy for treatment of several malignancies, including small-cell lung
carcinoma (SCLC). Because the estimated glomerular filtration rate, and therefore
the carboplatin dose, is based on the serum creatinine level, dosing of
carboplatin for amputees is a challenge. This case report describes how serum
carboplatin levels were used to determine the most suitable carboplatin dose for
an amputee. The patient received four cycles of etoposide in combination with
carboplatin area under the curve = 5 mg.min/ml, with a dose reduction of 25% and
concurrent radiotherapy. The measured area under the curve was found to be 3.41
mg.min/ml, while the target area under the curve was 3.75 mg.min/ml (75% of 5
mg.min/ml). Therefore, for the next cycles, the carboplatin dose was calculated
using the Calvert formula. No recurrence of disease was seen within two years
after completion of therapy. This case demonstrates that therapeutic drug
monitoring can successfully be used to determine the carboplatin dose for an
amputee.
PMID- 24356804
TI - Acute puerperal uterine inversion.
PMID- 24356805
TI - Posterior reversible encephalopathy syndrome in children: report of three cases.
AB - PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is a condition
characterized by varying degrees of headache, nausea, vomiting, visual
disturbances, focal neurologic deficit, and seizures due to severe systemic
hypertension. The knowledge of secondary hypertension in children is most
commonly due to renal abnormalities, suggesting that the leading cause of PRES in
childhood is renal diseases. METHODS: Three pediatric patients who developed PRES
due to various underlying renal diseases were reviewed. RESULTS: The etiology of
hypertension of our patients was all renal problems including atrophic kidney,
hydronephrosis secondary to reflux nephropathia, nephrotic syndrome, and acute
poststreptococcal glomerulonephritis. While two of them had typical of the
parieto-occipital and frontoparietal involvement, the other had brain stem
involvement. All of the patients were recovered by the control of high blood
pressure. CONCLUSION: Primary involvement of the brain stem is rare in children.
PRES should be taken into account, especially in children with renal disease in
the appropriate clinical settings.
PMID- 24356806
TI - Attitudes towards vaccination against group B streptococcus in pregnancy.
PMID- 24356807
TI - Towards evidence-based dosing regimens in children on the basis of population
pharmacokinetic pharmacodynamic modelling.
AB - When growing up, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of
drugs change, which may alter the effect of drugs. To ensure optimal drug
efficacy and safety in paediatric care, PK and PD relationships of drugs need to
be explored in children. This article presents an outline on performing a
population PK/PD study and translating these results into rational dosing
regimens, with the development and prospective evaluation of PK/PD derived
evidence-based dosing regimen being discussed. Examples on amikacin, morphine and
busulfan are provided, showing how PK(/PD) modelling not only led to optimization
and individualization in paediatric clinical care for the specific drugs but also
to insight in maturation of organ systems involved. It is shown that the latter
results can subsequently be used as a basis for dosing of other drugs eliminated
through the same pathway. Ultimately, these efforts should lead to predictable
drug efficacy and safety across all age groups.
PMID- 24356808
TI - The influence of comedication on tacrolimus blood concentration in patients
subjected to kidney transplantation: a retrospective study.
AB - Tacrolimus is an immunosuppressant used for the prevention of kidney allograft
rejection. The effects of comedication on tacrolimus trough concentrations (TTC)
in kidney transplant recipients, subjected to basic immunosuppressant regime
consisting of tacrolimus, corticosteroids and mycophenolate mofetil were
investigated. This retrospective case series study involved 208 of these
patients, with the outpatient examination recorded in the database of patients,
at the unit of monitoring, with a total of 5,011 such examinations. Binary
logistic regression analysis has shown that calcium channel blockers, diuretics
and proton pump inhibitors (PPIs) significantly affected TTC (p < 0.001). PPIs
significantly increased the number of examinations in which the TTC were in the
recommended therapeutic range (from 5 to 15 ng/ml), as well as over the
therapeutic range (p < 0.0001). When calcium channel blockers were added to PPIs,
even more pronounced effect was obtained in comparison to triple-drug therapy
only (p < 0.0001). In case a diuretic was given with a PPI, a significantly
increased number of examinations with subtherapeutic TTC was observed when
compared with PPI only (p = 0.0203). The combination of calcium channel blockers,
diuretics and PPIs resulted in the number of examinations with TTC in the
recommended therapeutic range not being different from the number of examinations
with TTC in the triple-drug therapy only (p = 0.3829). beta-adrenergic
antagonists can be administered without fear of affecting the tacrolimus optimal
therapeutic concentrations. This was confirmed with all combinations of the
examined drugs used in patients subjected to kidney transplantation concomitantly
with beta blockers.
PMID- 24356809
TI - Turpentine oil induced inflammation decreases absorption and increases
distribution of phenacetin without altering its elimination process in rats.
AB - Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were
determined in normal and experimentally induced inflamed rats by turpentine oil
to know the role of inflammation on the pharmacokinetics of phenacetin and
formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats,
weighing about 200-250 g that were randomly divided into two groups consisting
six in each group. Rats in group I (control) received phenacetin (150 mg kg(-1),
PO) where as group II received phenacetin 12 h after induction of inflammation by
turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital
plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5,
2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and
analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on
plasma concentrations of phenacetin and its metabolite paracetamol, the
pharmacokinetic parameters were determined by compartmental methods. C(max) of
phenacetin was significantly (p < 0.01) decreased to 19.50 +/- 2.74 MUg mL(-1) in
inflamed conditions compared to 38.13 +/- 2.20 MUg mL(-1) obtained in normal
rats. Except, for significant (p < 0.001) increase in volume of distribution at
steady state (V(dss)) from 2.87 +/- 0.37 to 8.03 +/- 1.26 L kg(-1) and increased
the rate of absorption with shorter absorption half-life (t(1/2ka)) for
phenacetin in inflammation. None of the pharmacokinetic parameters of either
phenacetin or its metabolite paracetamol were affected. It can be concluded that
turpentine oil induced inflammation has no role on the activity of CYP1A2 in
rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol
were found unaltered.
PMID- 24356810
TI - Regulation of anergy-related ubiquitin E3 ligase, GRAIL, in murine models of
colitis and patients with Crohn's disease.
AB - BACKGROUND: Abrogating tolerance is a critical step in the pathogenesis of
Crohn's disease (CD). T cell-anergy is one of the main mechanisms of tolerance
and is regulated by the gene related to anergy in lymphocytes (GRAIL). This study
investigated the expressions and regulation of GRAIL in CD and murine colitis
models. METHODS: Expressions of GRAIL mRNA and protein in CD4+ T cells were
investigated in the peripheral blood and mucosal tissues of patients with CD,
mice with dextran sodium salt (DSS)-induced colitis, and Il-10-deficient mice.
MicroRNAs responsible for the regulation of GRAIL were examined by miRNA
microarray. GRAIL-overexpressing T cells were intravenously injected in mice with
DSS-induced colitis. RESULTS: The GRAIL expression was higher in the lamina
propria (LP) CD4+ T cells of CD patients than of the control subjects, while it
was lower in the peripheral blood CD4+ T cells of the CD patients than of the
control subjects. The GRAIL mRNA expression was lower, but the GRAIL protein
expression was higher in the LP of colitic mice than that of non-colitic mice.
The miRNA microarray identified miR-290-5p as an miRNA that inhibits expression
of the GRAIL protein and that is highly expressed in the LP of non-colitic mice.
GRAIL-expressing T cells expressed regulatory T cell markers and showed
suppressive effects in murine DSS-induced colitis. CONCLUSIONS: Our results show
that expression of GRAIL is uniquely regulated by the specific miRNA in the
intestinal mucosa, and suggest that GRAIL may associate with the pathophysiology
of CD.
PMID- 24356811
TI - Once-daily simeprevir in combination with pegylated-interferon and ribavirin: a
new horizon in the era of direct-acting antiviral agent therapy for chronic
hepatitis C.
PMID- 24356812
TI - A proteomics-driven assay defines specific plasma protein signatures in different
stages of Meniere's disease.
AB - Meniere's disease (MD) is a common disorder of the inner ear whose hallmarks are
vertigo, tinnitus, aural fullness, and progressive hearing loss. The degree of
severity of the disease is quite heterogeneous, and so is its pathogenesis. A
multifactorial inheritance of intrinsic and extrinsic factors has been described,
but there is not a common agreement on the molecular basis of MD. In a recent
article, we have demonstrated that patients suffering from MD share a common
plasma proteomic signature, characterized by the presence of several up- and down
regulated proteins. In this study, we have further extended our analysis and show
that the differential expression of plasma proteins can identify specific subsets
of MD-affected individuals, depending on their stage. Our findings confirm our
plasma proteomics-driven approach as a powerful tool for early diagnosis of MD
and uncover a potentially starring role for some proteins in the development and
fate of this frustrating disease, whose pathogenesis still remains unclear.
PMID- 24356814
TI - Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38
MAPK with antitumor activity.
AB - p38alpha mitogen-activated protein kinase (MAPK) is activated in cancer cells in
response to environmental factors, oncogenic stress, radiation, and chemotherapy.
p38alpha MAPK phosphorylates a number of substrates, including MAPKAP-K2 (MK2),
and regulates the production of cytokines in the tumor microenvironment, such as
TNF-alpha, interleukin-1beta (IL-1beta), IL-6, and CXCL8 (IL-8). p38alpha MAPK is
highly expressed in human cancers and may play a role in tumor growth, invasion,
metastasis, and drug resistance. LY2228820 dimesylate (hereafter LY2228820), a
trisubstituted imidazole derivative, is a potent and selective, ATP-competitive
inhibitor of the alpha- and beta-isoforms of p38 MAPK in vitro (IC(50) = 5.3 and
3.2 nmol/L, respectively). In cell-based assays, LY2228820 potently and
selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated
HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse
RAW264.7 macrophages (IC(50) = 35.3 nmol/L) with no changes in phosphorylation of
p38alpha MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc <= 10 MUmol/L. LY2228820 also
reduced TNF-alpha secretion by lipopolysaccharide/IFN-gamma-stimulated
macrophages (IC(50) = 6.3 nmol/L). In mice transplanted with B16-F10 melanoma,
tumor phospho-MK2 (p-MK2) was inhibited by LY2228820 in a dose-dependent manner
[threshold effective dose (TED)(70) = 11.2 mg/kg]. Significant target inhibition
(>40% reduction in p-MK2) was maintained for 4 to 8 hours following a single 10
mg/kg oral dose. LY2228820 produced significant tumor growth delay in multiple in
vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma,
myeloma, breast). In summary, LY2228820 is a p38 MAPK inhibitor, which has been
optimized for potency, selectivity, drug-like properties (such as oral
bioavailability), and efficacy in animal models of human cancer.
PMID- 24356813
TI - Stereospecific PARP trapping by BMN 673 and comparison with olaparib and
rucaparib.
AB - Anti-PARP drugs were initially developed as catalytic inhibitors to block the
repair of DNA single-strand breaks. We recently reported that several PARP
inhibitors have an additional cytotoxic mechanism by trapping PARP-DNA complexes,
and that both olaparib and niraparib act as PARP poisons at pharmacologic
concentrations. Therefore, we have proposed that PARP inhibitors should be
evaluated based both on catalytic PARP inhibition and PARP-DNA trapping. Here, we
evaluated the novel PARP inhibitor, BMN 673, and compared its effects on PARP1
and PARP2 with two other clinical PARP inhibitors, olaparib and rucaparib, using
biochemical and cellular assays in genetically modified chicken DT40 and human
cancer cell lines. Although BMN 673, olaparib, and rucaparib are comparable at
inhibiting PARP catalytic activity, BMN 673 is ~100-fold more potent at trapping
PARP-DNA complexes and more cytotoxic as single agent than olaparib, whereas
olaparib and rucaparib show similar potencies in trapping PARP-DNA complexes. The
high level of resistance of PARP1/2 knockout cells to BMN 673 demonstrates the
selectivity of BMN 673 for PARP1/2. Moreover, we show that BMN 673 acts by
stereospecific binding to PARP1 as its enantiomer, LT674, is several orders of
magnitude less efficient. BMN 673 is also approximately 100-fold more cytotoxic
than olaparib and rucaparib in combination with the DNA alkylating agents methyl
methane sulfonate (MMS) and temozolomide. Our study demonstrates that BMN 673 is
the most potent clinical PARP inhibitor tested to date with the highest
efficiency at trapping PARP-DNA complexes.
PMID- 24356815
TI - Activation of AR sensitizes breast carcinomas to NVP-BEZ235's therapeutic effect
mediated by PTEN and KLLN upregulation.
AB - NVP-BEZ235 is a newly developed dual PI3K/mTOR inhibitor, being tested in
multiple clinical trials, including breast cancer. NVP-BEZ235 selectively induces
cell growth inhibition in a subset, but not all, breast cancer cell lines.
However, it remains a challenge to distinguish between sensitive and resistant
tumors, particularly in the pretreatment setting. Here, we used ten breast cancer
cell lines to compare NVP-BEZ235 sensitivity and in the context of androgen
receptor (AR) activation during NVP-BEZ235 treatment. We also used female SCID
mice bearing breast tumor xenografts to investigate the beneficial effect of
dihydrotestosterone/NVP-BEZ235 combination treatment compared with each alone. We
found that AR-positive breast cancer cell lines are much more sensitive to NVP
BEZ235 compared with AR-negative cells, regardless of PTEN or PI3KCA status.
Reintroducing AR expression in NVP-BEZ235 nonresponsive AR-negative cells
restored the response. DHT/NVP-BEZ235 combination not only resulted in a more
significant growth inhibition than either drug alone, but also achieved tumor
regression and complete responses for AR(+)/ER(+) tumors. This beneficial effect
was mediated by dihydrotestosterone (DHT)-induced PTEN and KLLN expression.
Furthermore, DHT could also reverse NVP-BEZ235-induced side effects such as skin
rash and weight loss. Our data suggest that AR expression may be an independent
predictive biomarker for response to NVP-BEZ235. AR induction could add benefit
during NVP-BEZ235 treatment in patients, especially with AR(+)/ER(+) breast
carcinomas.
PMID- 24356816
TI - Cancer-associated CD43 glycoforms as target of immunotherapy.
AB - CD43 is a sialoglycosylated membrane protein that is involved in cell
proliferation and differentiation. CD43 glycoforms that are recognized by the UN1
monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid
tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while
unexpressed in the normal counterparts. The cancer association of UN1/CD43
epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and
therapy. In this study, we show that the UN1 mAb was endowed with antitumor
activity in vivo because its passive transfer inhibited the growth of UN1
positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that
tumor inhibition was due to UN1 mAb-dependent natural killer-mediated
cytotoxicity. By screening a phage-displayed random peptide library, we
identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a
peptide sequence that was specifically recognized by the UN1 mAb and inhibited
the binding of the UN1 mAb to UN1-positive tumor cells. On the basis of sequence
homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165
peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope.
When used as vaccine in mice, the 2/165 phagotope raised antibodies against the
UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen
structure, and could represent a novel immunogen for cancer immunotherapy. These
findings support the feasibility of using monoclonal antibodies to identify
cancer-associated mimotopes for immunotherapy.
PMID- 24356817
TI - Glioblastoma cells containing mutations in the cohesin component STAG2 are
sensitive to PARP inhibition.
AB - Recent data have identified STAG2, a core subunit of the multifunctional cohesin
complex, as a highly recurrently mutated gene in several types of cancer. We
sought to identify a therapeutic strategy to selectively target cancer cells
harboring inactivating mutations of STAG2 using two independent pairs of isogenic
glioblastoma cell lines containing either an endogenous mutant STAG2 allele or a
wild-type STAG2 allele restored by homologous recombination. We find that
mutations in STAG2 are associated with significantly increased sensitivity to
inhibitors of the DNA repair enzyme PARP. STAG2-mutated, PARP-inhibited cells
accumulated in G2 phase and had a higher percentage of micronuclei, fragmented
nuclei, and chromatin bridges compared with wild-type STAG2 cells. We also
observed more 53BP1 foci in STAG2-mutated glioblastoma cells, suggesting that
these cells have defects in DNA repair. Furthermore, cells with mutations in
STAG2 were more sensitive than cells with wild-type STAG2 when PARP inhibitors
were used in combination with DNA-damaging agents. These data suggest that PARP
is a potential target for tumors harboring inactivating mutations in STAG2, and
strongly recommend that STAG2 status be determined and correlated with
therapeutic response to PARP inhibitors, both prospectively and retrospectively,
in clinical trials.
PMID- 24356818
TI - The effect of photoimmunotherapy followed by liposomal daunorubicin in a mixed
tumor model: a demonstration of the super-enhanced permeability and retention
effect after photoimmunotherapy.
AB - In general, de novo solid tumors are composed of phenotypically and functionally
heterogeneous malignant cells. This heterogeneity interferes with the
effectiveness of targeted molecular cancer therapies. Even if most of the tumor
is killed by a targeted treatment, recurrences are common and can be lethal. In
this study, a mixed tumor model, which is predominantly a population of epidermal
growth factor receptor (EGFR)-positive A431 cells combined with a smaller
population of EGFR-negative Balb3T3/DsRed cells, was established. This mixed
tumor was then treated with photoimmunotherapy, a newly developed target-cell
selective cancer therapy using a monoclonal antibody (mAb)-photosensitizer (IR700
fluorescence dye) conjugate and exposure of near-infrared light. Although
photoimmunotherapy successfully treated EGFR-positive A431 cells in the mixed
tumor, EGFR-negative Balb/DsRed cells were not responsive. However,
photoimmunotherapy also induced a large increase in tumor permeability, known as
the super-enhanced permeability and retention (SUPR) effect, which allowed a 5
fold increase in the accumulation of a liposomal chemotherapy (DaunoXome) and
resulted in more effective therapy than either photoimmunotherapy or liposomal
daunorubicin alone. The liposomal daunorubicin, administered 1 hour after EGFR
targeted photoimmunotherapy, was homogeneously distributed, allowing delivery to
tiny surviving nests of EGFR-negative Balb3T3/DsRed cells, resulting in prolonged
survival of mice.
PMID- 24356819
TI - [Complications after hip osteotomy].
AB - Complex deformities of the acetabulum are one of the most common reasons for
secondary pelvic osteoarthritis. One option of treatment is osteotomy of the
acetabulum close to the joint. The correction of the spatially reduced roof of
the femoral head resulting from pelvic dysplasia can minimize the risk of
developing secondary osteoarthritis or reduce the progression of an already
existing osteoarthritis. The Ganz periacetabular osteotomy (PAO) and Tonnis
triple osteotomy procedures are the predominant methods used to correct hip
dysplasia in adolescents. Both are complex procedures which bear specific risks
and complications, thus requiring very experienced surgeons.
PMID- 24356821
TI - Complete genome sequences of two waterfowl-origin tembusu virus strains isolated
in shandong province, china.
AB - Here, we report the complete genome sequences of two tembusu virus strains, ZC-1
and LQ-1, isolated from ducks and geese, respectively, in 2012. Phylogenetic
analysis showed that the nucleotide and amino acid sequences of the two strains
are closely related to those of the TMUV isolates around Shandong province. The
full-length genome sequences of two waterfowl-origin TMUVs provided herein will
help to understand the molecular epidemiology of tembusu virus in China, which
deserves further investigation.
PMID- 24356822
TI - Complete Genome of Salmonella enterica Serovar Typhimurium Myophage Maynard.
AB - Salmonella enterica serovar Typhimurium is a pathogenic bacterium that has been a
major concern for food and public safety. Phages infecting S. Typhimurium may
prove to be useful therapeutics against this harmful bacterium. Here, we announce
the complete genome of S. Typhimurium T4-like myophage Maynard and describe its
features.
PMID- 24356820
TI - [Complications of metal-on-metal tribological pairing].
AB - BACKGROUND: Metal-on-metal (MoM) tribological pairing results in less volumetric
abrasion than pairing with the conventionally used polyethylene and is associated
with a lower risk of material failure compared to other hard-hard pairings. An
increased frequency of problem cases in recent years has led to a great increase
in uncertainty. Against this background in this article the current aspects of
epidemiology, etiology, diagnostics and treatment of complications in MoM hip
joint endoprostheses will be discussed. EPIDEMIOLOGY AND ETIOLOGY: Based on the
results from national endoprosthesis registers and selected clinical studies an
evaluation of the rate of local complications from MoM tribological pairings was
undertaken. A differentiation was made between MoM pairings in pedicled small
head prostheses (<= 32 mm), large head (> 32 mm) and surface replacement (OFE)
endoprostheses. Each year MoM endoprostheses release on average 10(12)-10(14)
cobalt (Co) and chromium (Cr) nanoparticles per patient. This release of metal
ions and particles can lead to a variety of tissue reactions. DIAGNOSTICS: A
differentiation must be made between regular routine diagnostics within the
framework of implant follow-up screening and specific investigations due to the
occurrence of complaints. The diagnostics for patients treated with MoM hip
endoprostheses consists of a standardized step-wise approach considering possible
differential diagnoses and the utilization of modern laboratory chemical and
radiological methods. When problems occur, a differentiation should
preferentially be made between complaints not caused by metal and mechanical
problems (e.g. prosthesis loosening and impingement) and symptoms due to
periprosthetic infections. THERAPY OF COMPLICATIONS: The normal standards for hip
endoprosthetics are also valid for periprosthetic infections, fractures and other
general complications. Specific measures are, however, necessary for
complications due to metal-specific risks.
PMID- 24356823
TI - Draft Genome Sequence of Ralstonia solanacearum Race 4 Biovar 4 Strain SD54.
AB - Ralstonia solanacearum is an important etiological agent that can cause serious
bacterial wilt in a very wide range of potential host plants, including ginger.
Here, we report the complete genome sequence of R. solanacearum SD54, a race 4
biovar 4 (R4B4) strain from a diseased ginger plant in China.
PMID- 24356824
TI - Draft Genome Sequence of Pseudozyma brasiliensis sp. nov. Strain GHG001, a High
Producer of Endo-1,4-Xylanase Isolated from an Insect Pest of Sugarcane.
AB - Here, we present the nuclear and mitochondrial genome sequences of Pseudozyma
brasiliensis sp. nov. strain GHG001. P. brasiliensis sp. nov. is the closest
relative of Pseudozyma vetiver. P. brasiliensis sp. nov. is capable of growing on
xylose or xylan as a sole carbon source and has great biotechnological potential.
PMID- 24356825
TI - Complete Genome of Bacillus subtilis Myophage CampHawk.
AB - The study of bacteriophages infecting the model organism Bacillus subtilis has
provided an abundance of general knowledge and a platform for advances in
biotechnology. Here, we announce the annotated genome of CampHawk, a B. subtilis
phage. CampHawk was found to be an SPO1-like phage with similar gene content and
arrangement.
PMID- 24356826
TI - Draft genome sequences for oil-degrading bacterial strains from beach sands
impacted by the deepwater horizon oil spill.
AB - We report the draft genome sequences of 10 proteobacterial strains isolated from
beach sands contaminated with crude oil discharged from the Deepwater Horizon
spill, which were cultivated under aerobic and anaerobic conditions with crude
oil as the sole carbon source. All strains contain multiple putative genes
belonging to hydrocarbon degradation pathways.
PMID- 24356827
TI - Draft Genome Sequence of a Multidrug-Resistant New Delhi Metallo-beta-Lactamase-1
(NDM-1)-Producing Escherichia coli Isolate Obtained in Singapore.
AB - We report the draft genome sequence of a New Delhi metallo-beta-lactamase-1 (NDM
1)-positive Escherichia coli isolate obtained from a surgical patient. The
assembled data indicate the presence of 3 multidrug resistance plasmids, 1 of
which shares 100% identity with an NDM-1 plasmid isolated previously from a
nearby hospital, suggesting possible local transmission.
PMID- 24356828
TI - Draft Genome Sequence of Sodium-Independent Alkaliphilic Microbacterium sp.
Strain TS-1.
AB - Alkaliphilic Microbacterium sp. strain TS-1, newly isolated from the jumping
spider, showed Na(+)-independent growth and motility. Here, we report the draft
genome sequence of this bacterium, which may provide beneficial information for
Na(+)-independent alkaline adaptation mechanisms.
PMID- 24356829
TI - Draft Genome Sequences of Human Pathogenic Fungus Geomyces pannorum Sensu Lato
and Bat White Nose Syndrome Pathogen Geomyces (Pseudogymnoascus) destructans.
AB - We report the draft genome sequences of Geomyces pannorum sensu lato and Geomyces
(Pseudogymnoascus) destructans. G. pannorum has a larger proteome than G.
destructans, containing more proteins with ascribed enzymatic functions. This
dichotomy in the genomes of related psychrophilic fungi is a valuable target for
defining their distinct saprobic and pathogenic attributes.
PMID- 24356830
TI - Full-Length Genome Sequence of a Plaque-Cloned Virulent Porcine Epidemic Diarrhea
Virus Isolate (USA/Iowa/18984/2013) from a Midwestern U.S. Swine Herd.
AB - Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time
in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013)
was obtained from a diarrheic piglet. The isolate is genetically close to other
previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when
inoculated into neonatal pigs.
PMID- 24356831
TI - Complete Genome Sequence of Exiguobacterium sp. Strain MH3, Isolated from
Rhizosphere of Lemna minor.
AB - We report the complete genome sequence of Exiguobacterium sp. strain MH3,
isolated from the rhizosphere of duckweed. The genome assembly is 3.16 Mb, with a
G+C content of 47.24%, and it may provide useful information about plant-microbe
interactions and the genetic basis for the tolerance of the strain to various
environmental stresses.
PMID- 24356832
TI - Genome Sequence of Strain MOLA814, a Proteorhodopsin-Containing Representative of
the Betaproteobacteria Common in the Ocean.
AB - Strain MOLA814 is a marine betaproteobacterium that was isolated from seawater in
the Beaufort Sea. Here, we present its genome sequence and annotation. Genome
analysis revealed the presence of a proteorhodopsin-encoding sequence together
with its retinal-producing pathway, indicating that this strain might generate
energy by using light.
PMID- 24356833
TI - Complete Genome Sequence of Bacteroidales Strain CF from a Chloroform
Dechlorinating Enrichment Culture.
AB - Bacteroidales strain CF is the most abundant nondechlorinating organism in a
Dehalobacter-containing enrichment culture that consistently reductively
dechlorinates >50 mg/liter chloroform or 1,1,1-trichloroethane (methyl
chloroform). We assembled and closed the complete genome sequence of this
organism from the metagenomic sequencing data for enrichment cultures. This
organism is predicted to ferment l-lactate and ethanol.
PMID- 24356834
TI - Complete Genome Sequence of a Multidrug-Resistant Salmonella enterica Serovar
Typhimurium var. 5- Strain Isolated from Chicken Breast.
AB - Salmonella enterica subsp. enterica serovar Typhimurium is a leading cause of
salmonellosis. Here, we report a closed genome sequence, including sequences of 3
plasmids, of Salmonella serovar Typhimurium var. 5- CFSAN001921 (National
Antimicrobial Resistance Monitoring System [NARMS] strain ID N30688), which was
isolated from chicken breast meat and shows resistance to 10 different
antimicrobials. Whole-genome and plasmid sequence analyses of this isolate will
help enhance our understanding of this pathogenic multidrug-resistant serovar.
PMID- 24356835
TI - Draft Genome Sequence of NDM-1-Producing Klebsiella pneumoniae Clinical Isolate
303K.
AB - Multidrug-resistant New Delhi metallo-beta-lactamase 1 (NDM-1)-producing bacteria
have spread globally and become a major clinical and public health threat. We
report here the draft genome sequence of the Klebsiella pneumoniae clinical
isolate 303K, harboring an NDM-1 coding sequence.
PMID- 24356836
TI - Draft Genome Sequence of Lactobacillus crispatus EM-LC1, an Isolate with
Antimicrobial Activity Cultured from an Elderly Subject.
AB - Here we report the 1.86-Mb draft genome sequence of Lactobacillus crispatus EM
LC1, a fecal isolate with antimicrobial activity. This genome sequence is
expected to provide insights into the antimicrobial activity of L. crispatus and
improve our knowledge of its potential probiotic traits.
PMID- 24356837
TI - Draft Genome Sequences of Two Strains of Propionibacterium acnes Isolated from
Radical Prostatectomy Specimens.
AB - Propionibacterium acnes is a Gram-positive bacterium that is closely associated
with various parts of the human body, in particular with sebaceous follicles of
the skin. It has also been frequently isolated from diseased human prostates.
Here, we report draft genome sequences of two P. acnes strains, P6 and PA2,
isolated from radical prostatectomy specimens.
PMID- 24356838
TI - Draft Genome Sequence of the Arsenite-Oxidizing Strain Aliihoeflea sp. 2WW,
Isolated from Arsenic-Contaminated Groundwater.
AB - Here, we report the draft genome sequence of the arsenite-oxidizing bacterium
Aliihoeflea sp. strain 2WW, which consists of a 4.15-Mb chromosome and contains
different genes that are involved in arsenic transformations.
PMID- 24356839
TI - Genome Sequences of 28 Bordetella pertussis U.S. Outbreak Strains Dating from
2010 to 2012.
AB - Despite the availability of highly effective vaccines, Bordetella pertussis
incidence has been rapidly rising in highly vaccinated populations. Recent
outbreaks have received media attention, feeding concerns about the emergence of
dangerous new strains with increased virulence or that escape vaccine-induced
immunity. To accelerate the study of this reemerging pathogen, we sequenced the
genomes of 28 B. pertussis strains isolated during outbreaks from 2010 through
2012, making both strains and sequence data available to the scientific
community.
PMID- 24356840
TI - Complete genome sequence of a novel pigeon torque teno virus in china.
AB - Torque teno virus is a nonenveloped single-stranded DNA virus infecting humans
and nonprimate species. We report the complete genome sequence of a pigeon torque
teno virus isolated from pigeons in Jiangsu Province, China, in 2012. This genome
sequence will be useful for viral diagnostics and disease control.
PMID- 24356841
TI - Draft Genome Sequence of the Methanotrophic Gammaproteobacterium Methyloglobulus
morosus DSM 22980 Strain KoM1.
AB - Here, we report the draft genome sequence of the methanotrophic
gammaproteobacterium Methyloglobulus morosus DSM 22980 strain KoM1, which is
proposed to be the type species for the novel genus Methyloglobulus. The genome
(4.143 Mb) consists of a single circular chromosome and harbors genes for 2
aminoethylphosphonate (ciliatine) biosynthesis.
PMID- 24356842
TI - Draft genome sequence of pseudomonas strain p818, isolated from glyphosate
polluted soil.
AB - Pseudomonas strain P818 was isolated from glyphosate-polluted soil in China. This
bacterium presents a capacity for high glyphosate tolerance. We present the draft
genome sequence of the strain Pseudomonas P818. The genes involved in the
glyphosate tolerance were identified. This genomic information will facilitate
the study of glyphosate tolerance mechanisms.
PMID- 24356843
TI - Complete Genome Sequence of Bacillus toyonensis BCT-7112T, the Active Ingredient
of the Feed Additive Preparation Toyocerin.
AB - Strain BCT-7112, previously identified as Bacillus cereus var. toyoi, is the type
strain of the species Bacillus toyonensis, a novel species of the B. cereus
group. The complete genome of this strain, which is the active ingredient of the
feed additive preparation Toyocerin, has been sequenced and annotated to reveal
the genetic properties of this probiotic organism with a long history of safe use
in animal nutrition.
PMID- 24356844
TI - Draft Genome Sequence of Klebsiella pneumoniae Strain KP-1.
AB - Klebsiella pneumoniae is ubiquitous in the environment and is a member of a three
species biofilm model. We compared the genome sequence of an environmental
isolate, K. pneumoniae strain KP-1, to those of two clinical strains (NTUH-K2044
and MGH 78578). KP-1 possesses strain-specific prophage sequences that
distinguish it from the clinical strains.
PMID- 24356845
TI - High-Quality Draft Genome Sequence of Bifidobacterium longum E18, Isolated from a
Healthy Adult.
AB - Bifidobacteria are important gastrointestinal commensals of a number of animals,
including humans, and various beneficial effects on host health have been
attributed to them. Here, we announce the noncontiguous finished genome sequence
of Bifidobacterium longum E18, isolated from a healthy adult, which reveals
traits involved in its interaction with the host.
PMID- 24356846
TI - Complete Genome Sequence of Bacillus subtilis Strain PY79.
AB - Bacillus subtilis is a Gram-positive soil-dwelling and endospore-forming
bacterium in the phylum Firmicutes. B. subtilis strain PY79 is a prototrophic
laboratory strain that has been highly used for studying a wide variety of
cellular pathways. Here, we announce the complete whole-genome sequence of B.
subtilis PY79.
PMID- 24356847
TI - Draft Genome Sequence of Strain X47-2AL, a Feline Helicobacter pylori Isolate.
AB - Helicobacter pylori is a human-specific pathogen that exclusively inhabits the
human gastric mucosa. However, occasionally, humans transmit H. pylori to
susceptible animal hosts bred in colonies. Here, we report the genome sequence of
strain X47-2AL, isolated from a domestic cat and used in anti-H. pylori
immunization studies.
PMID- 24356848
TI - Draft Genome Sequence of the Obligate Halophilic Bacillus sp. Strain NSP22.2,
Isolated from a Seasonal Salt Marsh of the Great Rann of Kutch, India.
AB - Here, we report the 4.0-Mbp draft genome of an obligate halophile, Bacillus sp.
strain NSP22.2, isolated from a seasonal salt marsh of the Great Rann of Kutch,
India. To understand the mechanism(s) of obligate halophilism and to isolate the
relevant gene(s), the genome of Bacillus sp. NSP22.2 was sequenced.
PMID- 24356850
TI - Induction of skin lesions by ultraviolet B irradiation in a case of pemphigus
erythematosus.
PMID- 24356849
TI - Paternal autistic traits are predictive of infants visual attention.
AB - Since subthreshold autistic social impairments aggregate in family members, and
since attentional dysfunctions appear to be one of the earliest cognitive markers
of children with autism, we investigated in the general population the
relationship between infants' attentional functioning and the autistic traits
measured in their parents. Orienting and alerting attention systems were measured
in 8-month-old infants using a spatial cueing paradigm. Results showed that only
paternal autistic traits were linked to their children's: (1) attentional
disengagement; (2) rapid attentional orienting and (3) alerting. Our findings
suggest that an early dysfunction of orienting and alerting systems might alter
the developmental trajectory of future ability in social cognition and
communication.
PMID- 24356851
TI - New 2,6-distyryl-substituted BODIPY isomers: synthesis, photophysical properties,
and theoretical calculations.
AB - A 2,6-distyryl-substituted boradiazaindacene (BODIPY) dye and a new series of 2,6
p-dimethylaminostyrene isomers containing both alpha- and beta-position styryl
substituents were synthesized by reacting styrene and p-dimethylaminostyrene with
an electron-rich diiodo-BODIPY. The dyes were characterized by X-ray
crystallography and NMR spectroscopy and their photophysical properties were
investigated and analyzed by carrying out a series of theoretical calculations.
The absorption spectra contain markedly redshifted absorbance bands due to
conjugation between the styryl moieties and the main BODIPY fluorophore. Very low
fluorescence quantum yields and significant Stokes shifts are observed for 2,6
distyryl-substituted BODIPYs, relative to analogous 3,5-distyryl- and 1,7
distyryl-substituted BODIPYs. Although the fluorescence of the compound with beta
position styryl substituents on both pyrrole moieties and one with both beta- and
alpha-position substituents was completely quenched, the compound with only alpha
position substituents exhibits weak emission in polar solvents, but moderately
intense emission with a quantum yield of 0.49 in hexane. Protonation studies have
demonstrated that these 2,6-p-dimethylaminostyrene isomers can be used as sensors
for changes in pH. Theoretical calculations provide strong evidence that styryl
rotation and the formation of non-emissive charge-separated S1 states play a
pivotal role in shaping the fluorescence properties of these dyes. Molecular
orbital theory is used as a conceptual framework to describe the electronic
structures of the BODIPY core and an analysis of the angular nodal patterns
provides a reasonable explanation for why the introduction of substituents at
different positions on the BODIPY core has markedly differing effects.
PMID- 24356852
TI - Molecular sequelae of topographically guided peripheral nerve repair.
AB - Peripheral nerve injuries cause severe disability with decreased nerve function
often followed by neuropathic pain that impacts the quality of life. Even though
use of autografts is the current gold standard, nerve conduits fabricated from
electrospun nanofibers have shown promise to successfully bridge critical length
nerve gaps. However, in depth analysis of the role of topographical cues in the
context of spatio-temporal progression of the regenerative sequence has not been
elucidated. Here, we explored the influence of topographical cues (aligned,
random, and smooth films) on the regenerative sequence and potential to
successfully support nerve regeneration in critical size gaps. A number of key
findings emerged at the cellular, cytokine and molecular levels from the study.
Higher quantities of IL-1alpha and TNF-alpha were detected in aligned fiber based
scaffolds. Differential gene expression of BDNF, NGFR, ErbB2, and ErbB3 were
observed suggesting a role for these genes in influencing Schwann cell migration,
myelination, etc. that impact the regeneration in various topographies. Fibrin
matrix stabilization and arrest of nerve-innervated muscle atrophy was also
evident. Taken together, our data shed light on the cascade of events that favor
regeneration in aligned topography and should stimulate research to further
refine the strategy of nerve regeneration using topographical cues.
PMID- 24356853
TI - Influence of spreading and contractility on cell detachment.
AB - Cell adhesion is a key phenomenon that affects fundamental cellular processes
such as morphology, migration, and differentiation. In the current study, an
active modelling framework incorporating actin cytoskeleton remodelling and
contractility, combined with a cohesive zone model to simulate debonding at the
cell-substrate interface, is implemented to investigate the increased resistance
to detachment of highly spread chondrocytes from a substrate, as observed
experimentally by Huang et al. (J. Orthop. Res. 21: 88-95, 2003). 3D finite
element meshes of the round and spread cell geometries with the same material
properties are created. It is demonstrated that spread cells with a flattened
morphology and a larger adhesion area have a more highly developed actin
cytoskeleton than rounded cells. Rounded cells provide less support for tension
generated by the actin cytoskeleton; hence, a high level of dissociation is
predicted. It is revealed that the more highly developed active contractile actin
cytoskeleton of the spread cell increases the resistance to shear deformation,
and subsequently increases the shear detachment force. These findings provide new
insight into the link between cell geometry, cell contractility, and cell
substrate detachment.
PMID- 24356854
TI - Substance P and neurokinin 1 receptors as potential therapeutic targets in
children with OSA.
AB - BACKGROUND: Increased substance P (SP) levels and abundant expression of
neurokinin (NK) 1 receptor in adenotonsillar tissues of children with OSA but not
recurrent tonsillar infection (RI) suggest that NK1 antagonists could be useful
in treating OSA. METHODS: The effects of SP and the NK1 antagonist GR-82334 were
examined on mixed cell cultures prepared from dissociated tonsils harvested
intraoperatively from children with OSA and RI. Proliferation was assessed by
[3H]-thymidine or 5-ethynyl-2'-deoxyuridine incorporation, and inflammatory
cytokine production (tumor necrosis factor [TNF]-alpha, IL-6, IL-1beta) was
assessed in supernatants by enzyme-linked immunosorbent assay. RESULTS: SP
elicited dose-dependent increases in tonsillar cell proliferation in mixed cell
cultures from children with OSA but not with RI (P < .0001). The NK1 antagonist
exhibited dose-dependent reductions in cellular proliferative rates in OSA
derived cell cultures but not in RI-derived mixed cell cultures (P < .00001). SP
treatment was associated with increased TNF-alpha and IL-6 production, and GR
82334 abrogated SP effects, as well as reduced basal cytokine release (P <
.0001). CONCLUSIONS: SP pathways appear to underlie intrinsic proliferative and
inflammatory signaling pathways in tonsillar tissues from children with OSA but
not with RI. Selective disruption of these pathways may provide nonsurgical
alternatives for prevention and treatment of pediatric OSA.
PMID- 24356855
TI - Application of magnetic resonance spectroscopy in patients with alternating
hemiplegia of childhood: findings on metabolic dysfunctions.
AB - OBJECTIVE: Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental
syndrome of uncertain etiology. Although the use of magnetic resonance
spectroscopy (MRS) for the study of neurologic diseases has grown rapidly over
the past decade, its use for AHC patients is quite new. This study was aimed at
investigating changes of brain metabolites in patients with alternating
hemiplegia of childhood (AHC) during the hemiplegic ictal phases and interictal
phases by proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: (1)H-MRS
was used in AHC patients during the hemiplegic ictal phases and interictal phases
to evaluate functional activity in certain brain regions. A total of 10
unmedicated, healthy volunteers served as controls. RESULTS: N-acetylaspartate
(NAA)/Creatine(Cr) ratio of the frontal lobes, basal ganglia, and temporal lobes
in contralateral hemiplegic hemisphere of AHC patients during the ictal phases
was significantly lower than that in AHC patients during interictal phases and
control subjects. Significantly increased choline-containing compounds (Cho)/Cr
were obtained in corresponding regions. CONCLUSIONS: These findings suggest
neuronal metabolic dysfunctions in frontal lobes, temporal lobes and basal
ganglia in AHC patients during ictal phases that perhaps are involved in the
pathogenesis of AHC.
PMID- 24356856
TI - Secondary pediatric encephalocele after ventriculosubgaleal shunting for
posthemorrhagic hydrocephalus.
AB - Intraventricular hemorrhage and posthemorrhagic hydrocephalus continue to be
common complications in very low-birth-weight premature infants, often requiring
ventricular shunting for cerebrospinal fluid diversion. We report on two infants
with posthemorrhagic hydrocephalus that developed a secondary encephalocele after
ventriculosubgaleal shunting. Encephaloceles can act as a source of seizure
activity and can result in various additional complications including meningitis,
abscess formation, and infarction of herniated brain parenchyma. With continued
improvements in neonatal intensive care, the survival of infants with significant
medical comorbidities-including those that develop posthemorrhagic hydrocephalus
requiring ventricular shunting-continues to increase. It is thus important for
the radiologist and treating physician to be aware of this rare, potential
complication.
PMID- 24356857
TI - Novel mediators and biomarkers of thrombosis.
AB - Spurred by advances in understanding the molecular basis of thrombosis, this
issue of the Journal of Thrombosis and Thrombolysis is devoted to exploring
aspects of novel paradigms and their potential impact on diagnosis and treatment.
Complex interplay between blood and vascular cells, inflammation, and pro- and
anti-coagulant pathways determines the formation and stability of arterial and
venous thrombosis. A causal role for inflammation in coronary artery disease is
currently being tested in large clinical trials. Basic science observations
implicate inflammation in venous thromboembolic disorders and inflammatory
processes, may have a similar influence on device thrombosis. In this article and
throughout this issue of the Journal, we discuss biomarkers and mediators
associated with arterial and venous thrombosis, atrial fibrillation, and other
clinical scenarios.
PMID- 24356858
TI - Improvement of NMDA encephalitis by active lymph node removal.
PMID- 24356859
TI - Failed ventilation through the laryngeal mask airway.
PMID- 24356861
TI - Altered Tbx1 gene expression is associated with abnormal oesophageal development
in the adriamycin mouse model of oesophageal atresia/tracheo-oesophageal fistula.
AB - INTRODUCTION: Oesophageal atresia/tracheo-oesophageal atresia (OA/TOF) frequently
arises with associated anomalies and has been clinically linked with 22q11
deletion syndromes, a group of conditions due to Tbx1 gene mutation which include
Di George syndrome. Tbx1 and Tbx2 genes modulate pharyngeal and cardiac
development, but are also expressed in the developing foregut and are known to
interact with key signalling pathways described in oesophageal formation
including bone morphogenic proteins. The adriamycin mouse model (AMM) reliably
displays OA/TOF-like foregut malformations providing a powerful system for
investigating the disturbances in gene regulation and morphology involved in
tracheo-oesophageal malformations. We hypothesised that foregut abnormalities
observed in the AMM are associated with altered Tbx1 and Tbx2 gene expression.
METHODS: Time-mated CBA/Ca mice received intra-peritoneal injection of adriamycin
(for treated) or saline (for controls) on embryonic days (E)7 and 8. Untreated
Cd1 embryos were used to establish normal expression patterns. Embryos harvested
on E9-E11 underwent whole-mount in situ hybridization with labelled RNA probes
for Tbx1 and Tbx2. Optical projection tomography was used to visualise expression
in whole embryos by 3D imaging. RESULTS: Tbx1 expression was visualised in a
highly specific pattern in the proximal oesophageal endoderm in normal and
control embryos. In the AMM, extensive ectopic expression of Tbx1 was detected in
the dorsal foregut and adjacent to the TOF. The focally restricted oesophageal
expression pattern persisted in the AMM, but was posteriorly displaced in
relation to the tracheal bifurcation. Tbx2 was widely expressed in the ventral
foregut mesoderm of controls, lacking specific endoderm localisation. In the AMM,
altered Tbx2 expression in the foregut was only seen in severely affected
embryos. CONCLUSION: Highly specific Tbx1 expression in the proximal oesophageal
endoderm suggests that Tbx1 may be an important regulator of normal oesophageal
development. Altered Tbx1 expression in dorsal foregut and adjacent to the TOF in
the AMM suggests that Tbx1 gene disruption may contribute to the pathogenesis of
tracheo-oesophageal malformations.
PMID- 24356862
TI - Therapeutic drug monitoring-based dose optimisation of piperacillin and
meropenem: a randomised controlled trial.
AB - PURPOSE: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in
critically ill patients. Therapeutic drug monitoring (TDM) could overcome this
variability and increase PK target attainment. The objective of this study was to
analyse the effect of a dose-adaption strategy based on daily TDM on target
attainment. METHODS: This was a prospective, partially blinded, and randomised
controlled trial in patients with normal kidney function treated with meropenem
(MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily
TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic
(PK/PD) target was 100% fT>4MIC [percentage of time during a dosing interval that
the free (f) drug concentration exceeded 4 times the MIC]. The control group
received conventional treatment. The primary endpoint was the proportion of
patients that reached 100% fT>4MIC and 100 % fT>MIC at 72 h. RESULTS: Forty-one
patients (median age 56 years) were included in the study. Pneumonia was the
primary infectious diagnosis. At baseline, 100% fT>4MIC was achieved in 21% of
the PTZ patients and in none of the MEM patients; 100% fT>MIC was achieved in 71%
of the PTZ patients and 46 % of the MEM patients. Of the patients in the
intervention group, 76 % needed dose adaptation, and five required an additional
increase. At 72 h, target attainment rates for 100% fT>4MIC and 100% fT>MIC were
higher in the intervention group: 58 vs. 16%, p = 0.007 and 95 vs. 68%, p =
0.045, respectively. CONCLUSIONS: Among critically ill patients with normal
kidney function, a strategy of dose adaptation based on daily TDM led to an
increase in PK/PD target attainment compared to conventional dosing.
PMID- 24356863
TI - Gas-phase arylmethyl transfer and cyclodeamination of argentinated N-arylmethyl
pyridin-2-ylmethanimine.
AB - In collisional activation of argentinated N-arylmethyl-pyridin-2-ylmethanimine, a
neutral molecule of AgNH2 is eliminated, carrying one hydrogen from the methylene
and the other one from the ortho position (relative to the ipso carbon) of the
aryl ring. Taking argentinated N-benzyl-pyridin-2-ylmethanimine for example, the
proposition that the AgNH2 loss results from intramolecular arylmethyl transfer
combined with cyclodeamination is rationalized by deuterium labeling experiments,
blocking experiments, and theoretical calculations. The structure of the final
product ion from loss of AgNH2 was confirmed further by multistage mass
spectrometry.
PMID- 24356865
TI - Increased expression of S100A6 in malignant granular cell tumours.
PMID- 24356864
TI - Recognition of cytosolic DNA by cGAS and other STING-dependent sensors.
AB - The presence of DNA in the cytoplasm of mammalian cells is perceived as a danger
signal, alerting the host to the presence of microbial infection. In response to
the detection of cytoplasmic DNA, the immune system mounts a programed response
that involves the transcription of anti-viral genes such as type I interferons
and production of inflammatory cytokines such as IL-1beta. The recent discovery
of the cGAS-cGAMP second messenger pathway as well as IFI16 and additional
sensors collectively provide critical insights into the molecular basis behind
the sensing of cytoplasmic DNA. The insights obtained from these important
discoveries could unveil new avenues to understand host-immunity, improve vaccine
adjuvancy, and allow development of new treatments for inflammatory diseases
associated with abberrant sensing of DNA.
PMID- 24356866
TI - Catalytic and asymmetric fluorolactonisations of carboxylic acids through anion
phase transfer.
AB - Catalytic fluorolactonisations of aromatic carboxylic acids have been developed.
The reactions proceed under mild conditions using the commercially available
reagent Selectfluor. A weak phase transfer of the reagent mediated by Na2CO3
allows the reaction to be conducted in non-polar solvents. Furthermore, by the
use of a catalytic amount of (DHQ)2PHAL (hydroquinine 1,4-phthalazinediyl
diether), the first asymmetric fluorolactonisation has been achieved. The
corresponding isobenzofuran core can be found in many biologically active
molecules.
PMID- 24356867
TI - Intracellular glutathione content, developmental competence and expression of
apoptosis-related genes associated with G6PDH-activity in goat oocyte.
AB - PURPOSE: To associate glucose-6-phosphate dehydrogenase (G6PDH) activity in goat
oocytes with intracellular glutathione (GSH) content, meiotic competence,
developmental potential, and relative abundance of Bax and Bcl-2 genes
transcripts. METHODS: Goat oocytes were exposed to brilliant cresyl blue (BCB)
staining test and categorized into BCB(+) (blue-cytoplasm), and BCB(-) (colorless
cytoplasm) groups. A group of oocytes were not exposed to BCB test and was
considered as a control group. After maturation in vitro, a group of oocytes were
used for determination of nuclear status and intracellular GSH content while
another group was subjected to parthenogenetic activation followed by in vitro
embryo culture. RESULTS: We found that BCB(+) oocytes not only yielded higher
rate of maturation, but also showed an increased level of intracellular GSH
content than BCB(-) and control oocytes. Furthermore, BCB(+) oocytes produced
more blastocysts than BCB(-) and control oocytes. Our data revealed that the
expression of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes were
interacted with G6PDH-activity in mature oocyte, their surrounding cumulus cells,
and blastocyst-stage embryos. CONCLUSIONS: The results of this study demonstrate
that selection of goat oocytes based on G6PDH-activity through the BCB test
improves their developmental competence, increases intracellular GSH content, and
affects the expression of the apoptosis-related genes.
PMID- 24356868
TI - Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid
screening with high sensitivity.
AB - As an important biomarker and therapeutic target, telomerase has attracted
considerable attention concerning its detection and monitoring. Here, we present
a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase
activity detection method, which has several distinctive advantages. First,
colorimetric functionality allows rapid preliminary discrimination of telomerase
activity by the naked eye. Second, the employment of SERS technique results in
greatly improved detection sensitivity. Third, the combination of colorimetry and
SERS into one detection system can ensure highly efficacious and sensitive
screening of numerous samples. Besides, the avoidance of polymerase chain
reaction (PCR) procedures further guarantees fine reliability and simplicity.
Generally, the presented method is realized by an "elongate and capture"
procedure. To be specific, gold nanoparticles modified with Raman molecules and
telomeric repeat complementary oligonucleotide are employed as the colorimetric
SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized
with telomerase substrate oligonucleotide are used as the capturing substrate.
Telomerase can synthesize and elongate telomeric repeats onto the capturing
substrate. The elongated telomeric repeats subsequently facilitate capturing of
the reporting nanotag via hybridization between telomeric repeat and its
complementary strand. The captured nanotags can cause a significant difference in
the color and SERS intensity of the magnetically separated sediments. Thus both
the color and SERS can be used as indicators of the telomerase activity. With
fast screening ability and outstanding sensitivity, we anticipate that this
method would greatly promote practical application of telomerase-based early
stage cancer diagnosis.
PMID- 24356869
TI - Early male partnership patterns, social support, and sexual risk behavior among
young men who have sex with men.
AB - Few data exist on the early sexual behavior patterns of contemporary young men
who have sex with men (YMSM), the social context of these patterns, and which of
these factors influence risk for HIV and other sexually transmitted infections
(STI). We enrolled 94 YMSM (age 16-30) into a 1-year cohort study with serial
online retrospective surveys and HIV/STI testing. The first three partnerships of
YMSM were characterized by relatively high rates of unprotected anal sex and a
rapidly expanding sexual repertoire, but also increasing rates of HIV status
disclosure. During follow-up, 17 % of YMSM reported any nonconcordant unprotected
anal intercourse (NCUAI) and 15 % were newly diagnosed with HIV/STI. Sex
education in high school and current maternal support were protective against
HIV/STI, while isolation from family and friends was associated with recent
NCUAI. Social support-including from parents, peers, and school-based sex
education-may help mitigate HIV/STI risk in this population.
PMID- 24356870
TI - Further lignans from Saururus chinensis.
AB - Three new sauchinone analogues, sauchinones B-D (1-3), together with sauchinone
(4), were isolated from the aerial part of Saururus chinensis. Structures of the
new compounds were determined by extensive spectroscopic data as well as X-ray
analysis. Compounds 3 and 4 inhibited nitric oxide production in
lipopolysaccharide stimulated RAW 264.7 cells with IC50 values of 13.0 and 14.2
uM, respectively.
PMID- 24356871
TI - Isolation of major components from the roots of Godmania aesculifolia and
determination of their antifungal activities.
AB - From the methanol root extract of Godmania aesculifolia, a species selected in a
multinational OAS program aimed at discovering antifungal compounds from Latin
American plants, a new chavicol diglycoside (1), the known 3,4-dihydroxy-2-(3
methylbut-2-en-1-yl)-3,4-dihydronaphthalen-1(2H)-one (2), and lapachol (3) were
isolated and characterized by 1D and 2D NMR and MS techniques. Only 3 exhibited
fairly good activity against a panel of clinical isolates of Cryptococcus
neoformans (MIC50 between 7.8 and 31.2 ug/mL) and moderate activities against
Candida spp. and non-albicans Candida spp.
PMID- 24356872
TI - Alienusolin, a new 4alpha-deoxyphorbol ester derivative, and crotonimide C, a new
glutarimide alkaloid from the Kenyan Croton alienus.
AB - Two novel compounds, alienusolin, a 4alpha-deoxyphorbol ester (1), crotonimide C,
a glutarimide alkaloid derivative (2), and ten known compounds, julocrotine (3),
crotepoxide (4), monodeacetyl crotepoxide (5), dideacetylcrotepoxide, (6), beta
senepoxide (7), alpha-senepoxide (8), (+)-(2S,3R-diacetoxy-1
benzoyloxymethylenecyclohex-4,6-diene (9), benzyl benzoate (10), acetyl
aleuritolic (11), and 24-ethylcholesta-4,22-dien-3-one (12) were isolated from
the Kenyan Croton alienus. The structures of the compounds were determined using
NMR, GCMS, and HRESIMS studies.
PMID- 24356873
TI - Chemical constituents from Trichilia connaroides and their nitric oxide
production and alpha-glucosidase inhibitory activities.
AB - Phytochemical investigation of the stem and bark of Trichilia connaroides led to
the isolation of eight new nortriterpenoids (1-8), along with fifteen known
compounds (9-23). Their structures were established based on extensive
spectroscopic analysis. The absolute configuration of 2 was confirmed by X-ray
crystallographic study. The nitric oxide production and alpha-glucosidase
inhibitory effects for these isolates were evaluated: moderate to strong nitric
oxide production inhibitory activities were found for 5, 6, and 11-15, with IC50
values ranging from 7.5 to 26.3 uM; marked alpha-glucosidase inhibitory effects
were observed for 22 and 23, with IC50 values of 2.3 and 0.4 uM, respectively.
PMID- 24356874
TI - A new bis-labdanic diterpene from the rhizomes of Alpinia pahangensis.
AB - The rhizomes of Alpinia pahangensis yielded a new bis-labdanic diterpene for
which the name pahangensin C (1) was proposed along with twelve known analogues
(2-13). The structure of 1 was elucidated via spectroscopic methods including 1D
and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 2 and 12 were isolated
for the first time from the genus Alpinia. This is the second occurrence of
compounds 2 and 12 in the Zingiberaceae family. Selected analogues exhibited
moderate to strong inhibitory activity against Staphylococcus aureus and Bacillus
cereus.
PMID- 24356875
TI - A prospective study of estimated glomerular filtration rate and outcomes in
patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project.
AB - BACKGROUND: Atrial fibrillation (AF) is more likely to develop in patients with
chronic kidney disease (CKD) than in individuals with normal renal function, and
patients with CKD are more likely to suffer ischemic stroke (IS)/thromboembolism
(TE). To our knowledge, no prior study has considered the impact of estimated
glomerular filtration rate (eGFR) on bleeding. We investigated the relationship
of eGFR to IS/TE, mortality, and bleeding in an AF population unrestricted by age
or comorbidity. METHODS: Patients with nonvalvular AF (NVAF) were stratified into
five categories according to eGFR (>= 90, 60-89, 30-59, 15-29, and < 15
mL/min/1.73 m2), analyzing risk factors, all-cause mortality, bleeding, and
IS/TE. Of 8,962 eligible individuals, 5,912 had NVAF and available serum
creatinine data, with 14,499 patient-years of follow-up. RESULTS: The incidence
rates of IS/TE were 7.4 and 7.2 per 1,000 person-years in individuals not
receiving and receiving anticoagulation therapy, respectively. Rates of all-cause
mortality were 13.4 and 9.4 per 1,000 person-years, respectively, and of major
bleeding, 6.2 and 9.0 per 1,000 person-years, respectively. Rates increased with
decreasing eGFR, with IS/TE rates being lower in individuals receiving oral
anticoagulation (OAC) therapy. eGFR was not an independent predictor of IS/TE on
multivariate analyses. When the benefit of IS reduction is balanced against the
increased risk of hemorrhagic stroke, the net clinical benefit (NCB) was clearly
positive in favor of OAC use. CONCLUSIONS: Incidence rates of IS/TE, mortality,
and bleeding increased with reducing eGFR across the whole range of renal
function. OAC use was associated with a lower incidence of IS/TE and mortality at
1 year compared with individuals not receiving anticoagulants in all categories
of renal function as measured by eGFR. The NCB balancing IS against serious
bleeding was positive in favor of OAC use among patients with renal impairment.
PMID- 24356876
TI - Human uterine and placental arteries exhibit tissue-specific acute responses to
17beta-estradiol and estrogen-receptor-specific agonists.
AB - The discrete regulation of vascular tone in the human uterine and placental
circulations is a key determinant of appropriate uteroplacental blood perfusion
and pregnancy success. Humoral factors such as estrogen, which increases in the
placenta and maternal circulation throughout human pregnancy, may regulate these
vascular beds as studies of animal arteries have shown that 17beta-estradiol, or
agonists of estrogen receptors (ER), can exert acute vasodilatory actions. The
aim of this study was to compare how acute exposure to ER-specific agonists, and
17beta-estradiol, altered human placental and uterine arterial tone in vitro.
Uterine and placental arteries were isolated from biopsies obtained from women
with uncomplicated pregnancy delivering a singleton infant at term. Vessels were
mounted on a wire myograph, exposed to the thromboxane receptor agonist U46619
(10(-6) M), and then incubated with incremental doses (5 min, 0.03-30 uM) of
either 17beta-estradiol or agonists specific for the ERs ERalpha (PPT), ERbeta
(DPN) or the G-protein-coupled estrogen receptor GPER-1 (G1). ERalpha and ERbeta
mRNA expression was assessed. 17beta-estradiol, PPT and DPN each relaxed
myometrial arteries (P < 0.05) in a manner that was partly endothelium-dependent.
In contrast, 17beta-estradiol or DPN relaxed placental arteries (maximum
relaxation to 42 +/- 1.1 or 47.6 +/- 6.53% of preconstriction, respectively) to a
lesser extent than myometrial arteries (to 0.03 +/- 0.03 or 8.0 +/- 1.0%) and in
an endothelial-independent manner whereas PPT was without effect. G1 exposure did
not inhibit the constriction of myometrial nor placenta arteries. mRNA expression
of ERalpha and ERbeta was greater in myometrial arteries than placental arteries.
ER-specific agonists, and 17beta-estradiol, differentially modulate the tone of
uterine versus placental arteries highlighting that estrogen may regulate human
uteroplacental blood flow in a tissue-specific manner.
PMID- 24356877
TI - Regional differences in gender promotion and scholarly productivity in
otolaryngology.
AB - OBJECTIVES: To identify whether regional differences exist in gender disparities
in scholarly productivity and faculty rank among academic otolaryngologists.
STUDY DESIGN AND SETTING: Academic otolaryngologists' bibliometric data analyses.
METHODS: Online faculty listings from 98 otolaryngology departments were
organized by gender, academic rank, fellowship training status, and institutional
location. The Scopus database was used to assess bibliometrics of these
otolaryngologists, including the h-index, number of publications, and publication
experience. RESULTS: Analysis included 1127 otolaryngologists, 916 men (81.3%)
and 211 women (18.7%). Female faculty comprised 15.4% in the Midwest, 18.8% in
the Northeast, 21.3% in the South, and 19.0% in the West (P = .44). Overall, men
obtained significantly higher senior academic ranks (associate professor or
professor) compared to women (59.8% vs. 40.2%, P < .0001). Regional gender
differences in senior faculty were found in the South (59.8% men vs. 37.3% women,
P = .0003) and Northeast (56.4% men vs. 24.1% women, P < .0001) with concomitant
gender differences in scholarly impact, as measured by the h-index (South, P =
.0003; Northeast, P = .0001). Among geographic subdivisions, female
representation at senior ranks was lowest in the Mid-Atlantic (22.0%), New
England (30.8%), and West South Central (33.3%), while highest in Pacific (60.0%)
and Mountain (71.4%) regions. No regional gender differences were found in
fellowship training patterns (P-values > .05). CONCLUSION: Gender disparities in
academic rank and scholarly productivity exist most notably in the Northeast,
where women in otolaryngology are most underrepresented relative to men at senior
academic ranks and in scholarly productivity.
PMID- 24356878
TI - 1D nanorod-planted 3D inverse opal structures for use in dye-sensitized solar
cells.
AB - The effectiveness of the 1D nanorod (NR)-planted 3D inverse opal (IO) structure
as an electrode for dye-sensitized solar cells (DSSCs) is demonstrated here. The
NRs were grown on the surface of a macroporous IO structure and their
longitudinal growth increased the surface area of the structure proportional to
the growth duration. NR/IO electrodes with various NR growth times were compared.
A remarkable JSC was obtained for the DSSCs utilizing a NR/IO electrode. The
improvement of the JSC was analyzed in terms of its efficiency in light
harvesting and electron transport. The growth of the NRs improved the dye
adsorption density and scattering property of the electrode, resulting in an
improvement in the light harvesting efficiency. Electrochemical impedance
analysis revealed that the NRs also improved its electron transport properties.
Further growth of the NRs tended to limit the increase of the JSC, which could be
attributed to an overlap between them.
PMID- 24356879
TI - Sequence diversity of Pan troglodytes subspecies and the impact of WFDC6
selective constraints in reproductive immunity.
AB - Recent efforts have attempted to describe the population structure of common
chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P.
t. troglodytes, and P. t. schweinfurthii. However, few studies have pursued the
effects of natural selection in shaping their response to pathogens and
reproduction. Whey acidic protein (WAP) four-disulfide core domain (WFDC) genes
and neighboring semenogelin (SEMG) genes encode proteins with combined roles in
immunity and fertility. They display a strikingly high rate of amino acid
replacement (dN/dS), indicative of adaptive pressures during primate evolution.
In human populations, three signals of selection at the WFDC locus were
described, possibly influencing the proteolytic profile and antimicrobial
activities of the male reproductive tract. To evaluate the patterns of genomic
variation and selection at the WFDC locus in chimpanzees, we sequenced 17 WFDC
genes and 47 autosomal pseudogenes in 68 chimpanzees (15 P. t. troglodytes, 22 P.
t. verus, and 31 P. t. ellioti). We found a clear differentiation of P. t. verus
and estimated the divergence of P. t. troglodytes and P. t. ellioti subspecies in
0.173 Myr; further, at the WFDC locus we identified a signature of strong
selective constraints common to the three subspecies in WFDC6-a recent paralog of
the epididymal protease inhibitor EPPIN. Overall, chimpanzees and humans do not
display similar footprints of selection across the WFDC locus, possibly due to
different selective pressures between the two species related to immune response
and reproductive biology.
PMID- 24356880
TI - Involvement of the mitochondrial permeability transition pore in chronic ethanol
mediated liver injury in mice.
AB - Chronic ethanol consumption increases sensitivity of the mitochondrial
permeability transition (MPT) pore induction in liver. Ca(2+) promotes MPT pore
opening, and genetic ablation of cyclophilin D (CypD) increases the Ca(2+)
threshold for the MPT. We used wild-type (WT) and CypD-null (CypD(-/-)) mice fed
a control or an ethanol-containing diet to investigate the role of the MPT in
ethanol-mediated liver injury. Ca(2+)-mediated induction of the MPT and
mitochondrial respiration were measured in isolated liver mitochondria. Steatosis
was present in WT and CypD(-/-) mice fed ethanol and accompanied by increased
terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive
nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed
CypD(-/-) mice, as reflected by an increase in the ratio of microtubule protein 1
light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62
were measured in CypD(-/-) than WT mice. Ethanol decreased mitochondrial
respiratory control ratios and select complex activities in WT and CypD(-/-)
mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from
control- and ethanol-fed WT mice were more sensitive to Ca(2+)-mediated MPT pore
induction than mitochondria from their CypD(-/-) counterparts. Mitochondria from
ethanol-fed CypD(-/-) mice were also more sensitive to Ca(2+)-induced swelling
than mitochondria from control-fed CypD(-/-) mice but were less sensitive than
mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated
with impaired autophagy and did not prevent ethanol-mediated steatosis.
Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol
fed WT and CypD(-/-) mice. We conclude that chronic ethanol consumption likely
lowers the threshold for CypD-regulated and -independent characteristics of the
ethanol-mediated MPT pore in liver mitochondria.
PMID- 24356881
TI - Brain-derived neurotrophic factor enhances cholinergic contraction of
longitudinal muscle of rabbit intestine via activation of phospholipase C.
AB - Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of
proteins best known for its role in neuronal survival, differentiation,
migration, and synaptic plasticity in central and peripheral neurons. BDNF is
also widely expressed in nonneuronal tissues including the gastrointestinal
tract. The role of BDNF in intestinal smooth muscle contractility is not well
defined. The aim of this study was to identify the role of BDNF in carbachol
(CCh)- and substance P (SP)-induced contraction of intestinal longitudinal smooth
muscle. BDNF, selective tropomyosin-related kinase B (TrkB) receptor agonists,
and pharmacological inhibitors of signaling pathways were examined for their
effects on contraction of rabbit intestinal longitudinal muscle strips induced by
CCh and SP. BDNF activation of intracellular signaling pathways was examined by
Western blot in homogenates of muscle strips and isolated muscle cells. One-hour
preincubation with BDNF enhanced intestinal muscle contraction induced by CCh but
not by SP. The selective synthetic TrkB agonists LM 22A4 and 7,8-dihydroxyflavone
produced similar effects to BDNF. The Trk antagonist K-252a, a TrkB antibody but
not p75NTR antibody, blocked the effect of BDNF. The enhancement of CCh-induced
contraction by BDNF was blocked by the phospholipase C (PLC) antagonist U73122,
but not by ERK1/2 or Akt antagonists. Direct measurement in muscle strips and
isolated muscle cells showed that BDNF caused phosphorylation of TrkB receptors
and PLC-gamma, but not ERK1/2 or Akt. We conclude that exogenous BDNF augments
the CCh-induced contraction of longitudinal muscle from rabbit intestine by
activating TrkB receptors and subsequent PLC activation.
PMID- 24356883
TI - Inhibition of Toll-like receptor 4 suppresses liver injury induced by biliary
obstruction and subsequent intraportal lipopolysaccharide injection.
AB - The objective of this study was to elucidate the role of Toll-like receptor 4
(TLR4) in liver injury induced by biliary obstruction and subsequent intraportal
lipopolysaccharide (LPS) infusion in rats. Biliary obstruction often leads to the
development of bacterial translocation. Rats were subjected to either a sham
operation (Sham group) or bile duct ligation for 7 days (BDL group). Seven days
after each operation, LPS (0.5 MUg) was injected through the ileocecal vein. In
other experiments, rats that had undergone BDL were pretreated, before LPS
challenge, with internal biliary drainage (Drainage group); intravenous TAK-242,
a TLR4 inhibitor (TAK group); or intravenous GdCl3, a Kupffer cell deactivator
(GdCl3 group). The expression of the TLR4 protein and the number of Kupffer cells
in the liver were significantly increased in the BDL group compared with the Sham
group. These changes were normalized after biliary drainage. The expression of
TLR4 colocalized with Kupffer cells, which was confirmed by double
immunostaining. Serum levels of liver enzymes and proinflammatory cytokines after
intraportal LPS injection were significantly higher in the BDL group than in the
Sham group. However, pretreatment with TAK-242 or GdCl3 strongly attenuated these
changes to levels similar to those seen with biliary drainage. These results
imply that blocking TLR4 signaling effectively attenuates liver damage to the
same level as that observed with biliary drainage in rats with BDL and subsequent
intraportal LPS infusion. TAK-242 treatment may be used for patients who are
susceptible to liver damage by biliary obstruction and endotoxemia.
PMID- 24356882
TI - Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat
mesenteric venules by intervening in both trans- and paracellular pathway.
AB - Lipopolysaccharide (LPS) is one of the common pathogens that causes mesentery
hyperpermeability- and intestinal edema-related diseases. This study evaluated
whether ginsenoside Rb1 (Rb1), an ingredient of a Chinese medicine Panax ginseng,
has beneficial effects on mesentery microvascular hyperpermeability induced by
LPS and the underlying mechanisms. Male Wistar rats were continuously infused
with LPS (5 mg . kg(-1) . h(-1)) via the left jugular vein for 90 min. In some
rats, Rb1 (5 mg . kg(-1) . h(-1)) was administrated through the left jugular vein
30 min after LPS infusion. The dynamics of fluorescein isothiocynate-labeled
albumin leakage from mesentery venules was assessed by intravital microscopy.
Intestinal tissue edema was evaluated by hematoxylin and eosin staining. The
number of caveolae in endothelial cells of microvessels was examined by electron
microscopy. Confocal microscopy and Western blotting were applied to detect
caveolin-1 (Cav-1) expression and phosphorylation, junction-related proteins, and
concerning signaling proteins in intestinal tissues and human umbilical vein
endothelial cells. LPS infusion evoked an increased albumin leakage from
mesentery venules that was significantly ameliorated by Rb1 posttreatment.
Mortality and intestinal edema around microvessels were also reduced by Rb1. Rb1
decreased caveolae number in endothelial cells of microvessels. Cav-1 expression
and phosphorylation, VE-Cadherin phosphorylation, ZO-1 degradation, nuclear
factor-kappaB (NF-kappaB) activation, and Src kinase phosphorylation were
inhibited by Rb1. Rb1 ameliorated microvascular hyperpermeability after the onset
of endotoxemia and improved intestinal edema through inhibiting caveolae
formation and junction disruption, which was correlated to suppression of NF
kappaB and Src activation.
PMID- 24356884
TI - Key role of endothelial importin-alpha in VEGF expression and gastric
angiogenesis: novel insight into aging gastropathy.
AB - Recent in vivo studies demonstrated that aging gastric mucosa has impaired
angiogenesis and reduced expression of vascular endothelial growth factor (VEGF).
Angiogenesis is triggered by hypoxia and VEGF gene activation, and the latter
requires transport of transcription factor(s) into endothelial cell nuclei. We
focused on gastric mucosal endothelial cells (GMEC), which are key targets and
effectors of gastric angiogenesis, and determined whether and to what extent
importin-alpha, a nuclear transport protein, regulates VEGF gene activation and
gastric angiogenesis and the possible role of importin-alpha in aging
gastropathy. GMEC were isolated from rats 3 and 24 mo of age, young (YGEC) and
aging (AGEC), respectively. We examined in these cells 1) in vitro angiogenesis,
2) expression of VEGF and importin-alpha, 3) nuclear transport of hypoxia
inducible factor (HIF)-1alpha by importin-alpha, 4) binding of HIF-1alpha to the
VEGF gene promoter, and 5) effects of importin-alpha silencing in YGEC and its
upregulation in AGEC on angiogenesis and VEGF expression. AGEC exhibited
significantly impaired in vitro angiogenesis by fourfold and decreased expression
of VEGF, importin-alpha, and nuclear HIF-1alpha by 1.4-fold, 1.6-fold, and 2.9
fold, respectively, vs. YGEC. Upregulation of importin-alpha in AGEC
significantly reversed all these abnormalities. In YGEC, knockdown of importins
alpha1 and -alpha3 significantly reduced in vitro angiogenesis by 93% and 73% and
VEGF expression by 48% and 52%, respectively. The above findings demonstrate that
importin-alpha is a novel and critical regulator of gastric angiogenesis. Its
reduced expression in AGEC is the key mechanism for impaired angiogenesis and
reduced VEGF.
PMID- 24356885
TI - Therapeutic role of niacin in the prevention and regression of hepatic steatosis
in rat model of nonalcoholic fatty liver disease.
AB - Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage,
comprises a spectrum of liver abnormalities including the early fat deposition in
the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin
decreases plasma triglycerides, but its effect on hepatic steatosis is elusive.
To examine the effect of niacin on steatosis, rats were fed either a rodent
normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin
in the diet for 4 wk. For regression studies, rats were first fed the HF diet for
6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the
diet) while on the HF diet for 6 wk. The findings indicated that inclusion of
niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat
content, liver weight, hepatic oxidative products, and prevented hepatic
steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by
the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA
expression of fatty acid synthesis or oxidation genes (including sterol
regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid
synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA
levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a
key enzyme in triglyceride synthesis. These novel findings suggest that niacin
effectively prevents and causes the regression of experimental hepatic steatosis.
Approved niacin formulation(s) for other indications or niacin analogs may offer
a very cost-effective opportunity for the clinical development of niacin for
treating NAFLD and fatty liver disease.
PMID- 24356887
TI - Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-beta/Smad3
pathway.
AB - TGF-beta signaling plays an important role in the pathogenesis and progression of
chronic kidney disease (CKD). Smad3, a transcription factor, is a critical
fibrogenic mediator of TGF-beta. Sirt1 is a NAD(+) -dependent deacetylase that
has been reported to modify a number of transcription factors to exert certain
beneficial health effects. This study examined the effect of Sirt1 on Smad3 and
its role in CKD. Resveratrol attenuated the expression of extracelluar matrix
proteins in both the remnant kidney of 5/6th nephrectomized rats and cultured
mesangial cells (MMCs) exposed to TGF-beta1. The effect of resveratrol was
substantially attenuated in cultured MMCs for which Sirt1 had been knocked down
by an shRNA lentivirus. Overexpression of Sirt1 attenuated TGF-beta1-induced
extracelluar matrix expression in cultured cells. Co-immunoprecipitation studies
suggested that Sirt1 could bind with Smad3. Resveratrol treatment enhanced this
binding and reduced acetylation levels of Smad3. Resveratrol inhibited the
transcription activity of Smad3. Knockdown of Sirt1 increased acetylated Smad3
and substantially enhanced the transcriptional activity following TGF-beta1.
Finally, Sirt1 deficiency aggravated renal function damage and markedly enhanced
fibrosis in the remnant kidney of 5/6 nephrectomized mice. Taken together, these
results identify Sirt1 as an important protective factor for renal fibrosis in a
CKD rodent model, and the protective function of Sirt1 is attributable to its
action on TGF-beta/Smad3 signaling. Therefore, we suggest that Sirt1 may be a
potential therapeutic target for the treatment of CKD.
PMID- 24356886
TI - Xenin-25 delays gastric emptying and reduces postprandial glucose levels in
humans with and without type 2 diabetes.
AB - Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose
dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In
animals, Xen regulates gastrointestinal function and glucose homeostasis,
typically by initiating neural relays. However, little is known about Xen action
in humans. This study determines whether exogenously administered Xen modulates
gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion.
Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2
diabetes mellitus (T2DM; n = 10-14 per group) ingested a liquid mixed meal plus
acetaminophen (ACM; to assess gastric emptying) at time zero. On separate
occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen)
or 12 (Hi-Xen) pmol . kg(-1) . min(-1) was administered from zero until 300 min.
Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM,
glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP
1) levels were measured and ISRs calculated. Areas under the curves were compared
for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed
gastric emptying and reduced postprandial glucose levels in all groups. Infusions
for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma
GLP-1, but not GIP, levels without altering the insulin secretory response to
glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve
fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric
emptying in humans with and without T2DM, probably via a neural relay. Moreover,
endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy
humans under physiological conditions.
PMID- 24356889
TI - In situ growth of hierarchical SnO(2) nanosheet arrays on 3D macroporous
substrates as high-performance electrodes.
AB - Finding out how to overcome the self-aggregation of nanostructured electrode
materials is a very important issue in lithium-ion battery technology. Herein, by
an in situ construction strategy, hierarchical SnO2 nanosheet architectures have
been fabricated on a three-dimensional macroporous substrate, and thus the
aggregation of the SnO2 nanosheets was effectively prevented. The as-prepared
hierarchical SnO2 nanoarchitectures on the nickel foam can be directly used as an
integrated anode for lithium-ion batteries without the addition of other
ancillary materials such as carbon black or binder. In view of their apparent
advantages, such as high electroactive surface area, ultrathin sheet, robust
mechanical strength, shorter ion and electron transport path, and the specific
macroporous structure, the hierarchical SnO2 nanosheets exhibit excellent lithium
storage performance. Our present growth approach offers a new technique for the
design and synthesis of metal oxide hierarchical nanoarrays that are promising
for electrochemical energy-storage electrodes without carbon black and binder.
PMID- 24356888
TI - CD5 enhances Th17-cell differentiation by regulating IFN-gamma response and
RORgammat localization.
AB - Mechanisms that modulate the generation of Th17 cells are incompletely
understood. We report that the activation of casein kinase 2 (CK2) by CD5 is
essential for the efficient generation of Th17 cells in vitro and in vivo. In our
study, the CD5-CK2 signaling pathway enhanced TCR-induced activation of AKT and
promoted the differentiation of Th17 cells by two independent mechanisms:
inhibition of glycogen synthase kinase 3 (GSK3) and activation of mTOR. Genetic
ablation of the CD5-CK2 signaling pathway attenuated TCR-induced AKT activation
and consequently increased activity of GSK3 in Th17 cells. This resulted in
increased sensitivity of Th17 cells to IFN-gamma-mediated inhibition. In the
absence of CD5-CK2 signaling, we observed decreased activity of S6K and
attenuated nuclear translocation of RORgammat (ROR is retinoic acid receptor
related orphan receptor). These results reveal a novel and essential function of
the CD5-CK2 signaling pathway and GSK3-IFN-gamma axis in regulating Th-cell
differentiation and provide a possible means to dampen Th17-type responses in
autoimmune diseases.
PMID- 24356890
TI - Tuberculosis prevalence and risk factors for water buffalo in Para, Brazil.
AB - The prevalence of and possible risk factors for tuberculosis were studied in
water buffalo from Para, Brazil. In this study, 3,917 pregnant and nonpregnant
female Murrah and Mediterranean buffaloes were studied; 2,089 originated from
Marajo Island, and 1,108 were from the mainland. The comparative cervical
tuberculin test was used as a diagnostic test for tuberculosis in these animals.
The prevalence of positive buffaloes was 3.5 % (100/2,809) on Marajo Island and
7.2 % (80/1,108) on the mainland. The municipalities with the highest
tuberculosis prevalence rates in animals were Ipixuna do Para (10.1 %), Marapanim
(9.8 %), Chaves (9.4 %), Paragominas (8.6 %), and Cachoeira do Arari (6.7 %). The
tuberculosis prevalence was not significantly different between the Murrah (4.3
%) and Mediterranean (4.8 %) breeds or between pregnant (5 %) and nonpregnant
(4.3 %) buffaloes. Tuberculosis was detected in water buffaloes from Para,
Brazil; the mainland buffalo exhibited the highest tuberculosis prevalence. These
results indicate that this disease is dangerous to public health and buffalo
farming in Para.
PMID- 24356891
TI - Potato-associated arbuscular mycorrhizal fungal communities in the Peruvian
Andes.
AB - The world's fourth largest food crop, potato, originates in the Andes. Here, the
community composition of arbuscular mycorrhizal fungi (AMF) associated with
potato in Andean ecosystems is described for the first time. AMF were studied in
potato roots and rhizosphere soil at four different altitudes from 2,658 to 4,075
m above mean sea level (mamsl) and in three plant growth stages (emergence,
flowering, and senescence). AMF species were distinguished by sequencing an
approx. 1,500 bp nuclear rDNA region. Twenty species of AMF were identified, of
which 12 came from potato roots and 15 from rhizosphere soil. Seven species were
found in both roots and soil. Interestingly, altitude affected species
composition with the highest altitude exhibiting the greatest species diversity.
The three most common colonizers of potato roots detected were Funneliformis
mosseae, an unknown Claroideoglomus sp., and Rhizophagus irregularis. Notably,
the potato-associated AMF diversity observed in this Andean region is much higher
than that reported for potato in other ecosystems. Potato plants were colonized
by diverse species from 8 of the 11 Glomeromycota families. Identification of the
AMF species is important for their potential use in sustainable management
practices to improve potato production in the Andean region.
PMID- 24356893
TI - Surface-based analysis reveals regions of reduced cortical magnetization transfer
ratio in patients with multiple sclerosis: a proposed method for imaging subpial
demyelination.
AB - The in vivo detection of subpial cortical gray matter lesions in multiple
sclerosis is challenging. We quantified the spatial extent of subpial decreases
in the magnetization transfer ratio (MTR) of cortical gray matter in subjects
with multiple sclerosis, as such reductions may indicate regions of cortical
demyelination. We exploited the unique geometry of cortical lesions by using two
dimensional parametric surface models of the cortex instead of traditional three
dimensional voxel-wise analyses. MTR images were mapped onto intermediate
surfaces between the pial and white matter surfaces and were used to compute
differences between secondary-progressive MS (n = 12), relapsing-remitting MS (n
= 12), and normal control (n = 12) groups as well as between each individual
patient and the normal controls. We identified large regions of significantly
reduced cortical MTR in secondary-progressive patients when compared with normal
controls. We also identified large regions of reduced cortical MTR in 11
individual patients (8 secondary-progressive, 3 relapsing-remitting). The
secondary-progressive patients showed larger areas of abnormally low MTR compared
with relapsing-remitting patients both at the group level and on an individual
basis. The spatial distributions of abnormal MTR preferentially involved
cingulate cortex, insula, and the depths of sulci, in agreement with pathological
descriptions of subpial gray matter lesion distribution. These findings suggest
that our method is a plausible in vivo imaging technique for quantifying subpial
cortical demyelinating lesions in patients with multiple sclerosis and,
furthermore, can be applied at the typical clinical field strength of 1.5 T.
PMID- 24356892
TI - Resonance assignments of a membrane protein in phospholipid bilayers by combining
multiple strategies of oriented sample solid-state NMR.
AB - Oriented sample solid-state NMR spectroscopy can be used to determine the three
dimensional structures of membrane proteins in magnetically or mechanically
aligned lipid bilayers. The bottleneck for applying this technique to larger and
more challenging proteins is making resonance assignments, which is
conventionally accomplished through the preparation of multiple selectively
isotopically labeled samples and performing an analysis of residues in regular
secondary structure based on Polarity Index Slant Angle (PISA) Wheels and Dipolar
Waves. Here we report the complete resonance assignment of the full-length
mercury transporter, MerF, an 81-residue protein, which is challenging because of
overlapping PISA Wheel patterns from its two trans-membrane helices, by using a
combination of solid-state NMR techniques that improve the spectral resolution
and provide correlations between residues and resonances. These techniques
include experiments that take advantage of the improved resolution of the MSHOT4
Pi4/Pi pulse sequence; the transfer of resonance assignments through frequency
alignment of heteronuclear dipolar couplings, or through dipolar coupling
correlated isotropic chemical shift analysis; (15)N/(15)N dilute spin exchange
experiments; and the use of the proton-evolved local field experiment with
isotropic shift analysis to assign the irregular terminal and loop regions of the
protein, which is the major "blind spot" of the PISA Wheel/Dipolar Wave method.
PMID- 24356894
TI - Bladder exstrophy combined with uterovaginal prolapse and its surgical
management: case report and literature review.
AB - We describe a case of a postmenopausal woman with a corrected bladder exstrophy
(BE) who presented with a uterovaginal prolapse complicated by calcified fibroids
and discuss its surgical management. A 51-year-old woman presented with a
uterovaginal prolapse. She had previously had one full term delivery by caesarean
section 20 years ago. She had an ileal conduit performed for her BE at birth. A
computed tomography scan revealed significant pelvic anomaly and the uterus
contained multiple calcified fibroids. Due to the complexity of her condition the
surgical management was planned in two stages: initial examination under
anaesthetic in conjunction with a consultant urologist and then the definitive
planned reconstructive surgery. This case describes the need for careful
evaluation and planning of complex surgery and the successful surgical management
option for correction of uterovaginal prolapse in patients with BE. A vaginal
approach seemed to be a most sensible route to correct the prolapse in view of
her previous multiple abdominal surgeries.
PMID- 24356895
TI - Bladder perforation during sling procedures: diagnosis and management of injury.
AB - INTRODUCTION AND HYPOTHESIS: Midurethral slings are an effective and minimally
invasive treatment for stress urinary incontinence. One of the most common
intraoperative complications is bladder perforation, complicating between 2 and
10% of all operations, and on average 4.7%. It is usually corrected during
surgery, with repositioning of the trocars. The purpose of this video is to
demonstrate a method of replacing the trocars under direct vision. METHODS: This
video exhibits a bladder perforation during insertion of a retropubic midurethral
sling (Advantage Fit; Boston Scientific) and gives a step-by step guide to the
removal and repositioning of the sling under direct visualisation. CONCLUSION:
Repositioning of the trocars under direct vision in cases of bladder perforation
may have numerous advantages. It may prevent damage to the urethra, possibly
reduce the risk of postoperative infection and may be beneficial for trainees.
PMID- 24356896
TI - QM/MM study of the C-C coupling reaction mechanism of CYP121, an essential
cytochrome p450 of Mycobacterium tuberculosis.
AB - Among 20 p450s of Mycobacterium tuberculosis (Mt), CYP121 has received an
outstanding interest, not only due to its essentiality for bacterial viability
but also because it catalyzes an unusual carbon-carbon coupling reaction. Based
on the structure of the substrate bound enzyme, several reaction mechanisms were
proposed involving first Tyr radical formation, second Tyr radical formation, and
C-C coupling. Key and unknown features, being the nature of the species that
generate the first and second radicals, and the role played by the protein
scaffold each step. In the present work we have used classical and quantum based
computer simulation methods to study in detail its reaction mechanism. Our
results show that substrate binding promotes formation of the initial oxy
complex, Compound I is the responsible for first Tyr radical formation, and that
the second Tyr radical is formed subsequently, through a PCET reaction, promoted
by the presence of key residue Arg386. The final C-C coupling reaction possibly
occurs in bulk solution, thus yielding the product in one oxygen reduction cycle.
Our results thus contribute to a better comprehension of MtCYP121 reaction
mechanism, with direct implications for inhibitor design, and also contribute to
our general understanding of these type of enzymes.
PMID- 24356897
TI - Beware of false-negative CT scan for anastomotic leakage after colonic surgery.
AB - BACKGROUND: Anastomotic leakage is one of the most life-threatening complications
after colonic surgery. Correct diagnosis and treatment is important to reduce
morbidity and mortality. An abdominal CT scan is one of the main diagnostic tools
in diagnosing anastomotic leaks. The aim of this study was to examine the
accuracy of abdominal CT scanning to detect anastomotic leakage and to evaluate
the consequences of a false-negative CT outcome. METHODS: All consecutive
patients who underwent colonic resection for malignant disease between 2009 and
2011 or for benign disease in 2010 were reviewed. Patients in whom a
postoperative abdominal CT scan was performed to detect anastomotic leakage were
included. RESULTS: In 97 of 524 patients who underwent colonic surgery, an
abdominal CT scan was performed for the suspicion of anastomotic leakage. Overall
leakage rate was 10.9 % (n = 57). Mortality rate after leakage was 21.1 % (n =
12). Results from all abdominal CT scans revealed an overall sensitivity of 0.59
(95 % CI 0.43-0.73), a specificity of 0.88 (95 % CI 0.75-0.95), positive
predictive value 0.82 (95 % CI 0.64-0.92), negative predictive value 0.70 (95 %
CI 0.57-0.81), and an accuracy of 74 %. Delayed reintervention for anastomotic
leakage due to a false-negative CT outcome resulted in death in 62.5 % (n = 5).
CONCLUSION: The sensitivity of abdominal CT scanning after colonic surgery is
relatively low. A negative CT scan does not rule out anastomotic leakage. Even
with a negative CT scan, we should remain equally alert at clinical deterioration
as an argument for timely intervention.
PMID- 24356898
TI - Chaperone therapy for GM2 gangliosidosis: effects of pyrimethamine on beta
hexosaminidase activity in Sandhoff fibroblasts.
AB - Sphingolipidoses are inherited genetic diseases due to mutations in genes
encoding proteins involved in the lysosomal catabolism of sphingolipids. Despite
a low incidence of each individual disease, altogether, the number of patients
involved is relatively high and resolutive approaches for treatment are still
lacking. The chaperone therapy is one of the latest pharmacological approaches to
these storage diseases. This therapy allows the mutated protein to escape its
natural removal and to increase its quantity in lysosomes, thus partially
restoring the metabolic functions. Sandhoff disease is an autosomal recessive
inherited disorder resulting from beta-hexosaminidase deficiency and
characterized by large accumulation of GM2 ganglioside in brain. No enzymatic
replacement therapy is currently available, and the use of inhibitors of
glycosphingolipid biosynthesis for substrate reduction therapy, although very
promising, is associated with serious side effects. The chaperone pyrimethamine
has been proposed as a very promising drug in those cases characterized by a
residual enzyme activity. In this review, we report the effect of pyrimethamine
on the recovery of beta-hexosaminidase activity in cultured fibroblasts from
Sandhoff patients.
PMID- 24356900
TI - Examining relational empowerment for elementary school students in a yPAR
program.
AB - This paper joins relational empowerment, youth empowerment, and Bridging Multiple
Worlds frameworks to examine forms of relational empowerment for children in two
intermediary institutions-school and a youth participatory action research after
school program (yPAR ASP). Participants were twelve children, most of whom were
Latina/o and from im/migrant families, enrolled in a yPAR ASP for 2 years. A
mixed-method approach was utilized; we analyzed children's interviews, self
defined goals, and their social networks to examine their experiences of
relational empowerment. We conclude that children experienced each of the five
relational empowerment factors-collaborative competence, bridging social
divisions, facilitating others' empowerment, mobilizing networks, and passing on
a legacy-in the yPAR ASP setting, and some factors in school. These experiences,
however, were more pronounced in the yPAR ASP setting. Additionally, social
network analyses revealed that a small but meaningful percentage of actors
bridged worlds, especially home and family, but by year 2, also school and the
yPAR ASP. Finally, most helpers for school-based goals came from school, but a
sizable number came from family, friends, and home worlds, and by year 2, also
came from the yPAR ASP. Implications range from theoretical to methodological
development, including the use of social network analysis as a tool to
descriptively examine relational power in context.
PMID- 24356899
TI - (-)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by
adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice.
AB - Alzheimer's disease (AD) is pathologically characterized by deposition of beta
amyloid (Abeta) peptides, which closely correlates with the balance of nerve
growth factor (NGF)-related TrkA/p75NTR signaling. (-)-Epigallocatechin-3-gallate
(EGCG) is used for prevention and treatment of many neurodegenerative diseases,
including AD. However, whether the neuroprotective effects of EGCG treatment were
via modulating the balance of TrkA/p75NTR signaling was still unknown. In this
study, we found that EGCG treatment (2 mg.kg(-1).day(-1)) dramatically
ameliorated the cognitive impairments, reduced the overexpressions of Abeta(1-40)
and amyloid precursor protein (APP), and inhibited the neuronal apoptosis in the
APP/PS1 mice. Interestingly, the EGCG treatment enhanced the relative expression
level of NGF by increasing the NGF/proNGF ratio in the APP/PS1 mice. Moreover,
after EGCG treatment, TrkA signaling was activated by increasing the
phosphorylation of TrkA following the increased phosphorylation of c-Raf, ERK1/2,
and cAMP response element-binding protein (CREB), simultaneously the p75NTR
signaling was significantly inhibited by decreasing the p75ICD expression, JNK2
phosphorylation, and cleaved-caspase 3 expression, so that the Abeta deposits and
neuronal apoptosis in the hippocampus were inhibited.
PMID- 24356901
TI - Perceivers vary in their capacity to benefit from feedback in learning to
perceive length by dynamic touch.
AB - Earlier ecologically motivated studies have revealed substantial individual
differences in perceptual learning: Individuals varied in their ability to attune
to a specifying variable. A possible source of these individual differences is
between-subjects variation in the capacity to benefit from feedback. Although
this hypothesis was postulated by Withagen & van Wermeskerken (2009), their
experiment could not exclude other factors that might be involved. The aim of the
present experiment was to provide a more critical test of their hypothesis. To
this end, we trained two groups of participants in length perception by dynamic
touch in two different learning environments. In one environment, it was easier
for a perceiver to separate the perceptual noise from the error that resulted
from the detection of a nonspecifying variable. This separation was more
difficult to make in the other learning environment. All of the participants
responded to the feedback in the easy environment, but not all of them did in the
difficult environment. This indicates that individuals indeed differ in their
capacities to benefit from feedback. The implications of these results for recent
debates on individual differences are discussed.
PMID- 24356902
TI - Segmented heterochromia in a single scalp hair.
PMID- 24356903
TI - The RING domain of the scaffold protein Ste5 adopts a molten globular character
with high thermal and chemical stability.
AB - Ste5 is a scaffold protein that controls the pheromone response of the MAP-kinase
cascade in yeast cells. Upon pheromone stimulation, Ste5 (through its RING-H2
domain) interacts with the beta and gamma subunits of an activated heterodimeric
G protein and promotes activation of the MAP-kinase cascade. With structural and
biophysical studies, we show that the Ste5 RING-H2 domain exists as a molten
globule under native buffer conditions, in yeast extracts, and even in denaturing
conditions containing urea (7 M). Furthermore, it exhibits high thermal stability
in native conditions. Binding of the Ste5 RING-H2 domain to the physiological
Gbeta/gamma (Ste4/Ste18) ligand is accompanied by a conformational transition
into a better folded, more globular structure. This study reveals novel insights
into the folding mechanism and recruitment of binding partners by the Ste5 RING
H2 domain. We speculate that many RING domains may share a similar mechanism of
substrate recognition and molten-globule-like character.
PMID- 24356904
TI - Prognostic relevance of pulmonary arterial compliance in patients with chronic
heart failure.
AB - BACKGROUND: Reduced pulmonary arterial compliance (Ca) is a marker of poor
prognosis in idiopathic pulmonary arterial hypertension. We tested the hypothesis
that pulmonary arterial Ca could be a predictor of outcome in patients with
chronic heart failure (CHF). METHODS: We enrolled 306 patients with CHF due to
systolic left ventricular dysfunction (sLVD) who underwent a clinically driven
right-sided heart catheterization. Pulmonary arterial Ca was measured by the
ratio between stroke volume and pulse pressure (SV/PP). The primary end point was
cardiovascular death; secondary end point was the composite of cardiovascular
death, urgent heart transplantation, and appropriately detected and treated
episode of ventricular fibrillation. RESULTS: An inverse relationship was
observed between SV/PP and pulmonary vascular resistance, the mean resistance
compliance product (RC-time) being 0.30 +/- 0.2 s. In patients with pulmonary
capillary wedge pressure (PCWP) < 15 mm Hg, the mean RC-time was 0.34 +/- 0.14 s,
and in patients with PCWP >= 15 mm Hg it was 0.28 +/- 0.22 s. Eighty-seven
patients died in a follow-up period of 50 +/- 32 months. At receiver operating
characteristic curve analysis, the optimal prognostic cutoff point of SV/PP was
2.15 mL/mm Hg. An elevated (> 2.15) SV/PP was more strongly associated with
survival than any other hemodynamic variable; it was associated with poor
prognosis both in patients with high (P = .003) and in patients with normal
pulmonary vascular resistance (P = .005). CONCLUSIONS: Pulmonary arterial Ca is a
strong prognostic indicator in patients with CHF with sLVD. Most importantly, its
prognostic role is retained in patients with normal pulmonary vascular
resistance.
PMID- 24356905
TI - Inhibition of hepatitis C virus replication in vitro by xanthohumol, a natural
product present in hops.
AB - Hepatitis C virus is a major cause of chronic liver disease worldwide.
Xanthohumol, a prenylated flavonoid from hops, has various biological activities
including an antiviral effect. It was previously characterized as a compound that
inhibits bovine viral diarrhea virus, a surrogate model of hepatitis C virus. In
the present work, xanthohumol was examined for its ability to inhibit hepatitis C
virus replication in a cell culture system carrying replicating hepatitis C virus
RNA replicon. 0.2 % DMSO and 500 units/mL interferon-alpha treatments were set as
a negative and positive control, respectively. The inhibitory effect by
xanthohumol was determined by the luciferase activity of the infected Huh7.5 cell
lysates and the hepatitis C virus RNA levels in the culture. Xanthohumol at 3.53
uM significantly decreased the luciferase activity compared to the negative
control (p < 0.01). Xanthohumol at 7.05 uM further decreased the luciferase
activity compared to xanthohumol at 3.53 uM (p = 0.015). Xanthohumol at 7.05 uM
or 14.11 uM achieved an inhibitory effect similar to that of interferon-alpha 2b
(p > 0.05). Xanthohumol at 3.53 uM significantly reduced the hepatitis C virus
RNA level compared to the negative control (p = 0.001). Although the results of
xanthohumol at 7.05 uM had a higher variation, xanthohumol at the 7.05 uM and
14.11 uM decreased the hepatitis C virus RNA level to that achieved by interferon
alpha (p > 0.05). In conclusion, xanthohumol displays anti-hepatitis C virus
activity in a cell culture system and may be potentially used as an alternative
or complementary treatment against the hepatitis C virus.
PMID- 24356906
TI - Xanthones from Swertia mussotii and their alpha-glycosidase inhibitory
activities.
AB - Two new xanthones, 1,8-dihydroxy-3-methoxyxanthone 7-O-[alpha-L-rhamnopyranosyl(1
-> 2)-beta-D-glucopyranoside] (1) and 1,8- dihydroxy-3-methoxyxanthone 7-O-[alpha
L-rhamnopyranosyl(1 -> 3)-alpha-L-rhamno-pyranosyl (1 -> 2)-beta-D
xylopyranoside] (2), together with 26 known xanthones (3-28), were isolated from
the aqueous ethanol extract of the traditional Chinese herb Swertia mussotii.
Their structures were elucidated via spectroscopic analyses including 2D NMR. The
inhibition of alpha-glucosidase by the isolated xanthones was evaluated by an in
vitro high-throughput screening assay. Our results indicated that 1,3,5,8
tetrahydroxyxanthone is the best inhibitor with an IC50 value of 5.33 +/- 0.09
uM, while the O-glycosylated xanthones were poor alpha-glycosidase inhibitors.
PMID- 24356907
TI - Hepatoprotective triterpenoids and saponins of Schefflera kwangsiensis.
AB - Seven new triterpenoid saponins, schekwangsiensides A-G (1-7), and a new
triterpenoid, schekwangsienin (8), together with nine known triterpenoids and
saponins (9-17), were isolated from the aerial parts of Schefflera kwangsiensis.
The structures of these compounds were elucidated on the basis of spectroscopic
data analysis and chemical evidence. Furthermore, in in vitro assays, compounds
4, 8, 9, and 15 (10 uM) exhibited moderate hepatoprotective activities against D
galactosamine-induced HL-7702 cell damage.
PMID- 24356908
TI - Quadrangular prism: a unique self-assembly from amphiphilic hyperbranched PMA-b
PAA.
AB - The novel hyperbranched poly(methyl acrylate)-block-poly(acrylic acid)s (HBPMA-b
PAAs) are successfully synthesized via single-electron transfer-living radical
polymerization (SET-LRP), followed with hydrolysis reaction. The copolymer
solution could spontaneously form unimolecular micelles composed of the
hydrophobic core (PMA) and the hydrophilic shell (PAA) in water. Results show
that the size of spherical particles increases from 8.18 to 19.18 nm with
increased pH from 3.0 to 12.0. Most interestingly, the unique regular
quadrangular prisms with the large microstructure (5.70 MUm in length, and 0.47
MUm in width) are observed by the self-assembly of unimolecular micelles when pH
value is below 2. Such self-assembly behavior of HBPMA-b-PAA in solution is
significantly influenced by the pH cycle times and concentration, which show that
increased polymer concentration favors aggregate growth.
PMID- 24356910
TI - Identification of 4"-isovaleryl-spiramycin III produced by Bacillus sp. fmbJ.
AB - The production of secondary metabolites with antibiotic properties is a common
characteristic to Bacillus spp. These metabolites not only have diverse chemical
structures but also have a wide range of bioactivities with medicinal and
agricultural interests such as antibiotic. Bacillus sp. fmbJ has been found to
produce lipopeptides fengycin and surfactin in accordance with our previous
report. In this study, another antimicrobial substance was separated and purified
from the culture supernatant of strain fmbJ using the silica gel column
chromatography and preparative reversed-phase high-performance liquid
chromatography. By means of electrospray ionization mass spectroscopy, infrared
spectroscopy, and nuclear magnetic resonance, the antagonistic compound was
determined to be 4"-isovaleryl-spiramycin III with the molecular weight of 982
Da. This report is the first to introduce the finding of spiramycin produced from
Bacillus sp. The study provides a novel source for the production of spiramycin
in pharmaceutical industries.
PMID- 24356909
TI - Poincare plot analysis of autocorrelation function of RR intervals in patients
with acute myocardial infarction.
AB - The Poincare plot of RR intervals (RRI) is obtained by plotting RRIn+1 against
RRIn. The Pearson correlation coefficient (rhoRRI), slope (SRRI), Y-intercept
(YRRI), standard deviation of instantaneous beat-to-beat RRI variability (SD1RR),
and standard deviation of continuous long-term RRI variability (SD2RR) can be
defined to characterize the plot. Similarly, the Poincare plot of autocorrelation
function (ACF) of RRI can be obtained by plotting ACFk+1 against ACFk. The
corresponding Pearson correlation coefficient (rhoACF), slope (SACF), Y-intercept
(YACF), SD1ACF, and SD2ACF can be defined similarly to characterize the plot. By
comparing the indices of Poincare plots of RRI and ACF between patients with
acute myocardial infarction (AMI) and patients with patent coronary artery (PCA),
we found that the rhoACF and SACF were significantly larger, whereas the
RMSSDACF/SDACF and SD1ACF/SD2ACF were significantly smaller in AMI patients. The
rhoACF and SACF correlated significantly and negatively with normalized high
frequency power (nHFP), and significantly and positively with normalized very low
frequency power (nVLFP) of heart rate variability in both groups of patients. On
the contrary, the RMSSDACF/SDACF and SD1ACF/SD2ACF correlated significantly and
positively with nHFP, and significantly and negatively with nVLFP and low-/high
frequency power ratio (LHR) in both groups of patients. We concluded that the
rhoACF, SACF, RMSSDACF/SDACF, and SD1ACF/SD2ACF, among many other indices of ACF
Poincare plot, can be used to differentiate between patients with AMI and
patients with PCA, and that the increase in rhoACF and SACF and the decrease in
RMSSDACF/SDACF and SD1ACF/SD2ACF suggest an increased sympathetic and decreased
vagal modulations in both groups of patients.
PMID- 24356911
TI - Dynamics of hydrogen-producing bacteria in a repeated batch fermentation process
using lake sediment as inoculum.
AB - In this study, we evaluated the effectiveness of lake sediment as inoculum for
hydrogen production through dark fermentation in a repeated batch process. In
addition, we investigated the effect of heat treatment, applied to enrich
hydrogen-producing bacteria, on the bacterial composition and metabolism.
Denaturing gradient gel electrophoresis and molecular cloning, both performed
using the 16S rDNA gene as target gene, were used to monitor the structure of the
bacterial community. Hydrogen production and bacterial metabolism were analysed
via gas chromatography and high-performance liquid chromatography. Both treated
and non-treated inocula were able to produce high amounts of hydrogen. However,
statistical analysis showed a clear difference in their bacterial composition and
metabolism. The heat treatment favoured the growth of different Clostridia sp.,
in particular of Clostridium bifermentans, allowing the production of a constant
amount of hydrogen over prolonged time. These cultures showed both butyrate and
ethanol fermentation types. Absence of heat treatment allowed species belonging
to the genera Bacillus, Sporolactobacillus and Massilia to outgrow Clostridia sp.
with a reduction in hydrogen production and a significant metabolic change. Our
data indicate that lake sediment harbours bacteria that can efficiently produce
hydrogen over prolonged fermentation time. Moreover, we could show that the heat
treatment stabilizes the bacterial community composition and the hydrogen
production.
PMID- 24356912
TI - Crk at the quarter century mark: perspectives in signaling and cancer.
AB - The Crk adaptor protein, discovered 25 years ago as the transforming gene (v-crk)
product encoded by the CT10 avian retrovirus, has made a great impact on the
field of signal transduction. By encoding an oncoprotein that contained a viral
gag protein fused to only SH2 and SH3 domains, v-Crk demonstrated the
significance of SH2 and SH3 domains in oncogenic signaling by their virtue of
binding in a sequence-specific context to organize and assemble protein networks.
In more recent years, the cellular homologs of Crk (Crk II, Crk I, and CrkL) have
been extensively studied, and shown to have critical functions in a wide spectrum
of biological and pathological processes that include cell motility, invasion,
survival, bacterial pathogenesis, and the efferocytosis of apoptotic cells.
Clinically, Crk proteins are implicated in the aggressive behavior of human
cancers, including adenocarcinomas of the lung, breast, and stomach, as well as
in sarcomas and gliomas. Over-expression of Crk proteins in human cancers has led
to a renewed interest in both their signal transduction pathways and mechanisms
of up-regulation. This prospect summarizes recent developments in Crk biology,
including new structural and biochemical roles for the atypical carboxyl-terminal
SH3 (SH3C) domain, revelations regarding the molecular differences between Crk II
and Crk L, and the significance of Crk expression in stratified human tumor
samples.
PMID- 24356913
TI - Towards ideal synthesis: alkenylation of aryl C-H bonds by a Fujiwara-Moritani
reaction.
AB - An overview of recent progress in the Fujiwara-Moritani reaction, which is the
palladium-catalyzed oxidative coupling of arenes with olefins to afford alkenyl
arenes, is described. It is emphasized that regioselectivity on aryl ortho- or
meta-C?H activation could be controlled very well in the presence of Pd, Rh, or
Ru catalysts with the assistance of various chelation groups on aromatic rings in
this coupling reaction. Catalytic alkenylation of aryl C?H bonds from simple
arenes is also discussed, especially from electron-deficient arenes. These
advanced protocols would not only make the Fujiwara-Moritani reaction more useful
and applicable in organic synthesis but also light the way for the further
development of the functionalization of normal C?H bonds.
PMID- 24356916
TI - The C-terminal domain of the transcriptional regulator BldD from Streptomyces
coelicolor A3(2) constitutes a novel fold of winged-helix domains.
AB - BldD regulates transcription of key developmental genes in Streptomyces
coelicolor. While the N-terminal domain is responsible for both dimerization and
DNA binding, the structural and functional roles of the C-terminal domain (CTD)
remain largely unexplored. Here, the solution structure of the BldD-CTD shows a
novel winged-helix domain fold not compatible with DNA binding, due to the
negatively charged surface and presence of an additional helix. Meanwhile, a
small elongated groove with conserved hydrophobic patches surrounded by charged
residues suggests that the BldD-CTD could be involved in protein-protein
interactions that provide transcriptional regulation.
PMID- 24356917
TI - Stereocontrolled syntheses of tetralone- and naphthyl-type lignans by a one-pot
oxidative [3,3] rearrangement/Friedel-Crafts arylation.
AB - The development of a stereoselective one-pot oxidative [3,3] sigmatropic
rearrangement/Friedel-Crafts arylation that provides enantioenriched benzhydryl
compounds is reported. The utility of this new transformation is demonstrated by
the concise synthesis of several tetralone- and naphthyl-type lignan natural
products, many of which display anti-malarial activity.
PMID- 24356918
TI - Association between hyperlactatemia and occult cardiac failure in diabetic
patients on maintenance hemodialysis.
AB - PURPOSE: Lactic acidosis as a consequence of high serum lactate levels may deepen
the metabolic acidosis in patients with end-stage renal failure. Besides, certain
antidiabetic may also cause raised lactate levels in diabetic patients.
Therefore, it is obvious that the risk of hyperlactatemia is increased by folds
in diabetic patients on chronic hemodialysis program. In this study, it is aimed
to evaluate the frequency and the impact of increased serum lactate levels in
prevalent diabetic hemodialysis patients. METHODS: A total of 100 diabetic
patients who were under maintenance hemodialysis in five different dialysis
centers were included in this study. All biochemical parameters, blood gas
measurements, echocardiographic data and antidiabetic treatments were
statistically analyzed in terms of serum lactate levels. RESULTS: Out of 100
patients, 12 patients had serum lactate levels over normal limits. When the
patients with normal or high serum lactate levels were defined as two different
groups, statistical significance was detected between serum lactate levels and
serum sodium (p = 0.019), potassium (p = 0.037) and bicarbonate levels (p =
0.028). Moreover, in patients with hyperlactatemia, the ejection fraction value
was found significantly low (p = 0.005). CONCLUSIONS: The frequency of
hyperlactatemia was not rare in prevalent diabetic hemodialysis patients. We
additionally found that serum lactate level measurement may particularly help to
diagnose the occult cardiac failure. However, further large scale studies are
required to define the clinical significance of hyperlactatemia in the end-stage
renal failure patients with diabetes mellitus.
PMID- 24356919
TI - A feasibility study of peritoneum preservation in radical cystectomy with
extraperitonealization of orthotopic neobladder for invasive high-grade bladder
cancer: a preliminary analysis.
AB - OBJECTIVE: To describe a technique for radical cystectomy with
extraperitonealization of orthotopic neobladder (RCEN) that reduces bowel-related
complications by preservation of the peritoneum. MATERIALS AND METHODS: Fifteen
patients with non-metastatic bladder cancer underwent RCEN by a peritoneum
preserving technique. The study included 13 patients with T1 high-grade bladder
cancer and 2 with T2a bladder cancer. To compare perioperative outcomes including
bowel-related complications, we also reviewed 15 patients who underwent
traditional cystectomy with ileal Studer neobladder who were matched for age,
sex, body mass index, American Society of Anesthesiologists (ASA) score, tumor
stage, tumor grade, tumor size, and location. Female genital organs were
preserved in five female patients who underwent the RCEN technique. RESULTS:
There was no significant difference between the two cohorts (RECN vs. traditional
technique) with respect to age, body mass index, ASA score, or tumor
characteristics. The mean operative time was similar between the two groups. The
patients who underwent RECN exhibited earlier recovery of normal gas pattern on
plain abdominal X-ray during the postoperative period and an earlier resumption
of normal diet. The mean hospital stay was shorter in the RECN group than the
traditional group. CONCLUSIONS: The RECN technique preserving the whole
peritoneum is a feasible approach that significantly reduces bowel-related
complications in selected patients.
PMID- 24356920
TI - Efficacy of tegafur-uracil (UFT) administration in castration-resistant prostate
cancer patients with a history of both alternative antiandrogen therapy and
estramustine phosphate sodium hydrate therapy.
AB - PURPOSE: The purpose of this study was to evaluate the efficacy of tegafur-uracil
(UFT) administration as a fourth-line therapy in patients with castration
resistant prostate cancer (CRPC) who had already received combined androgen
blockade (CAB) therapy (first-line), alternative antiandrogen therapy (second
line), and estramustine phosphate sodium hydrate (EMP) therapy (third-line), in
order to determine who would benefit from UFT therapy. METHODS: UFT was
administered at a daily dose of 300 mg/m(2) to 26 patients, and the response to
UFT 4 weeks after its induction and its toxicity were evaluated. RESULTS: A
reduction in the serum prostate-specific antigen (PSA) value was observed in 12
patients (46.2 %), while two cases (7.7 %) achieved more than 50 % reduction in
PSA. Two patients (7.7 %) required discontinuation of UFT administration because
of side effects (grade 2 exanthema in one patient and grade 2 nausea in one
patient). A PSA response to UFT was observed, especially in patients older than
75 years and/or whose Gleason score was 8 or less. CONCLUSIONS: Our data indicate
that UFT administration as a fourth-line therapy was tolerable and effective to
some degree in patients with CRPC who had already received CAB therapy,
alternative antiandrogen therapy, and EMP therapy. It can be used, even in
patients aged more than 75 years old, without any loss of efficacy or effect on
their activities of daily life, and can be regarded as a treatment option for
patients with advanced prostate cancer.
PMID- 24356921
TI - Comparison of tick-borne microorganism communities in Ixodes spp. of the Ixodes
ricinus species complex at distinct geographical regions.
AB - Characterizing the tick-borne microorganism communities of Ixodes ricinus (sheep
tick) and Ixodes persulcatus (taiga tick) from the I. ricinus species complex in
distinct geographical regions of Eastern Europe and European Russia, we
demonstrated differences between the two ticks. Taiga ticks were more frequently
mono- and co-infected than sheep ticks: 24.4 % (45/184 tested ticks) versus 17.5
% (52/297) and 4.3 % (8/184) versus 3.4 % (10/297), respectively. Ginsberg co
infection index values were significant at the various sites. Diversity of the
tick-borne microorganism communities was estimated by the Shannon index, reaching
values of 1.71 +/- 0.46 and 1.20 +/- 0.15 at the sheep-tick and the taiga-tick
harbored sites, respectively. Richness of the tick-borne microorganism community
in the sheep tick collection sites was about twice the value of the taiga tick
collection sites. Future investigations are warranted to further characterize the
peculiarities of the tick-borne microorganism communities among the ticks of the
Ixodes ricinus complex.
PMID- 24356922
TI - Oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate
in acute bone fracture pain control: a double-blind placebo-controlled randomized
clinical trial.
AB - OBJECTIVES: Bone fracture is a common cause of acute pain in emergency and
orthopedics departments. Targeting the multifaceted mechanisms of pain with
combinations of multiple analgesics (multimodal analgesia) can increase the pain
control efforts efficacy and decrease the adverse effects of each medication.
METHODS: One hundred and fifty-three patients with acute bone fracture were
randomly allocated to two groups receiving intravenous morphine sulfate (74
patients) or oral oxycodone plus intravenous acetaminophen (79 patients). Pain
scores and drugs' adverse effects were assessed 10, 30 and 60 min after
treatment. RESULTS: Pain scores were similar between groups before, 30 and 60 min
after medication but patients in morphine sulfate group experienced less pain 10
min after medication. Eight (10.8%) patients in morphine sulfate group and 26
(32.9%) patients in acetaminophen/oxycodone group experienced nausea that was
statistically significant higher (P value = 0.001). Itching was seen in 12
(15.1%) patients of acetaminophen/oxycodone group and three (4.0%) patients of
patients in morphine sulfate group (P value = 0.02). CONCLUSION: Intravenous
acetaminophen plus oral oxycodone is as effective as intravenous morphine sulfate
in acute pain control in emergency department but with a less desirable safety
profile.
PMID- 24356923
TI - A cascade leading to premature aging phenotypes including abnormal tumor profiles
in Werner syndrome (review).
AB - This perspective review focused on the Werner syndrome (WS) by addressing the
issue of how a single mutation in a WRN gene encoding WRN DNA helicase induces a
wide range of premature aging phenotypes accompanied by an abnormal pattern of
tumors. The key event caused by WRN gene mutation is the dysfunction of
telomeres. Studies on normal aging have identified a molecular circuit in which
the dysfunction of telomeres caused by cellular aging activates the TP53 gene.
The resultant p53 suppresses cell growth and induces a shorter cellular lifespan,
and also compromises mitochondrial biogenesis leading to the overproduction of
reactive oxygen species (ROS) causing multiple aging phenotypes. As an analogy of
the mechanism in natural aging, we described a hypothetical mechanism of
premature aging in WS: telomere dysfunction induced by WRN mutation causes
multiple premature aging phenotypes of WS, including shortened cellular lifespan
and inflammation induced by ROS, such as diabetes mellitus. This model also
explains the relatively late onset of the disorder, at approximately age 20.
Telomere dysfunction in WS is closely correlated with abnormality in
tumorigenesis. Thus, the majority of wide and complex pathological phenotypes of
WS may be explained in a unified manner by the cascade beginning with telomere
dysfunction initiated by WRN gene mutation.
PMID- 24356924
TI - Concise review: Regulation of stem cell proliferation and differentiation by
essential fatty acids and their metabolites.
AB - Stem cell therapy holds great promise for regenerative medicine and the treatment
of numerous diseases. A key issue of stem cell therapy is the control of stem
cell fate, but safe and practical methods are limited. Essential fatty acids,
namely omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA), and
their metabolites are critical components of cell structure and function, and
could therefore influence stem cell fate. The available evidence demonstrates
that n-6 and n-3 PUFA and their metabolites can act through multiple mechanisms
to promote the proliferation and differentiation of various stem cell types.
Therefore, elucidating the role of PUFA and their metabolites in stem cell fate
regulation is both a challenge and an opportunity for stem cell biology as well
as stem cell therapy. PUFA-based interventions to create a favorable environment
for stem cell proliferation or differentiation may thus be a promising and
practical approach to controlling stem cell fate for clinical applications.
PMID- 24356925
TI - Viral inoculum dose impacts memory T-cell inflation.
AB - Memory T-cell inflation develops during certain persistent viral infections and
is characterized by the accumulation and maintenance of large numbers of effector
memory T cells, albeit with varying degrees in size and phenotype among infected
hosts. The underlying mechanisms that control memory T-cell inflation are not yet
fully understood. Here, we dissected CMV-specific memory T-cell formation and its
connection to the initial infectious dose by varying the inoculum size. After low
dose inoculum with mouse CMV, the accumulation of inflationary memory T cells was
severely hampered and correlated with reduced reservoirs of latent virus in
nonhematopoietic cells and diminished antigen-driven T-cell proliferation.
Moreover, lowering of the initial viral dose turned the characteristic effector
memory-like inflationary T cells into more central memory-like cells as evidenced
by the cell-surface phenotype of CD27(high) , CD62L(+) , CD127(+) , and KLRG1(-)
, and by improved secondary expansion potential. These data show the impact of
the viral inoculum on the degree of memory T-cell inflation and provide a
rationale for the observed variation of human CMV-specific T-cell responses in
terms of magnitude and phenotype.
PMID- 24356926
TI - Divergent dendrimer synthesis via the Passerini three-component reaction and
olefin cross-metathesis.
AB - The combination of the Passerini reaction and olefin cross-metathesis is shown to
be a very useful approach for the divergent synthesis of dendrimers. Castor oil
derived platform chemicals, such as 10-undecenoic acid and 10-undecenal, are
reacted in a Passerini reaction with an unsaturated isocyanide to obtain a core
unit having three terminal double bonds. Subsequent olefin cross-metathesis with
tert-butyl acrylate, followed by hydrogenation of the double bonds and hydrolysis
of the tert-butyl ester, leads to an active core unit bearing three carboxylic
acid groups as reactive sites. Iterative steps of the Passerini reaction with 10
undecenal and 10-isocyanodec-1-ene for branching, and olefin cross-metathesis
with tert-butyl acrylate, followed by hydrogenation and hydrolysis allow the
synthesis of a third-generation dendrimer. All steps of the synthesis are
carefully characterized by NMR, GPC, MS, and IR.
PMID- 24356927
TI - Contingent orienting or contingent capture: a size singleton matching the target
distractor size relation cannot capture attention.
AB - In the present study, we examined whether a peripheral size-singleton distractor
that matches the target-distractor size relation can capture attention and
disrupt central target identification. Three experiments consistently showed that
a size singleton that matches the target-distractor size relation cannot capture
attention when it appears outside of the attentional window, even though the same
size singleton produces a cuing effect. In addition, a color singleton that
matches the target color, instead of a size singleton that matches the target
distractor size relation, captures attention when it is outside of the
attentional window. Thus, a size-relation-matched distractor is much weaker than
a color-matched distractor in capturing attention and cannot capture attention
when the distractor appears outside of the attentional window.
PMID- 24356928
TI - Pathological gambling induced by dopamine antagonists: a case report.
AB - Pathological gambling is defined as inappropriate, persistent, and maladaptive
gambling behaviour. It is a non-pharmacological addiction classified as an
impulse control disorder. However, pathological gambling has been associated with
dopamine agonist use. Here we report of a 28-year-old man with a first major
depressive episode and a post-traumatic stress disorder who has been treated with
a combination of the serotonine/noradrenaline reuptake inhibitor duloxetine and
the tricyclic antidepressant maprotiline. The administration of antipsychotic
flupentixole (up to 7 mg) turned this slight online poker gambler into an
excessive gambler. Only after the discontinuation of the antidopaminergic agents
and the switch to bupropion did this gambling behaviour stop which suggests a
causal relationship between dopamine antagonists and pathological gambling.
PMID- 24356929
TI - Analysis of collagen organization in mouse achilles tendon using high-frequency
ultrasound imaging.
AB - Achilles tendon ruptures are traumatic injuries, and techniques for assessing
repair outcomes rely on patient-based measures of pain and function, which do not
directly assess tendon healing. Consequently, there is a need for a quantitative,
in vivo measure of tendon properties. Therefore, the purpose of this study was to
validate ultrasound imaging for evaluating collagen organization in tendons. In
this study, we compared our novel, high-frequency ultrasound (HFUS) imaging and
analysis method to a standard measure of collagen organization, crossed polarizer
(CP) imaging. Eighteen mouse Achilles tendons were harvested and placed into a
testing fixture where HFUS and CP imaging could be performed simultaneously in a
controlled loading environment. Two experiments were conducted: (1) effect of
loading on collagen alignment and (2) effect of an excisional injury on collagen
alignment. As expected, it was found that both the HFUS and CP methods could
reliably detect an increase in alignment with increasing load, as well as a
decrease in alignment with injury. This HFUS method demonstrates that structural
measures of collagen organization in tendon can be determined through ultrasound
imaging. This experiment also provides a mechanistic evaluation of tissue
structure that could potentially be used to develop a targeted approach to aid in
rehabilitation or monitor return to activity after tendon injury.
PMID- 24356930
TI - New insights into the role of erythrocytes in thrombus formation.
AB - The role of erythrocytes in thrombus formation has previously been regarded as
passive by their influence on rheology. Erythrocytes are known, due to their
abundance and size, to push platelets to the vascular wall (laminar shearing).
This results in an increased platelet delivery at the vascular wall enabling
platelets to seal off a vascular damage preventing excessive blood loss.
Recently, there is new evidence for erythrocytes to influence thrombus formation
in multiple ways besides their effect on rheology. Several groups have shown that
besides platelets, erythrocytes are the main suppliers of phosphatidylserine
exposing membranes needed for coagulation resulting in fibrin formation. In
addition, our group has found that the intercellular adhesion molecule 4
alphaIIbbeta3 interaction mediates erythrocyte-platelet interaction in flowing
blood. By inhibiting this interaction, we found decreased thrombin formation and
decreased incorporation of erythrocytes into a thrombus. This review will provide
more in-detail information of existing and new hypotheses regarding the role of
erythrocytes in thrombus formation.
PMID- 24356931
TI - Contraception-related venous thromboembolism in adolescents.
AB - Venous thromboembolism (VTE) is a rare but serious complication of combined
hormonal contraception. While the absolute risk of VTE is low in adolescents,
thrombotic events in contraception users younger than the age of 20 years account
for 5 to 10% of total contraception-related VTE events in population studies,
because of the high frequency of contraception use in adolescents. An increased
risk of VTE exists not only with oral contraceptives, but also the contraceptive
patch and vaginal ring. Most adolescents who experience contraception-related VTE
have additional transient or inherited thrombotic risk factors at the time of
VTE. Although the presence of inherited thrombophilia impacts the risk of
contraception-related VTE, thrombophilia screening before contraception
prescribing should be targeted only to high-risk populations. Pediatric
institutions, caregivers, and young women need to be aware of the risk of VTE
with estrogen-containing contraception, and maintain a high index of suspicion
for this complication in women using these agents.
PMID- 24356932
TI - Novel functional magnetic resonance imaging biomarkers for assessing response to
therapy in hepatocellular carcinoma.
AB - The established and adapted image biomarkers based on size for tumor burden
measurement continue to be applied to hepatocellular carcinoma (HCC) as size
measurement can easily be used in clinical practice. However, in the setting of
novel targeted therapies and liver directed treatments, simple tumor anatomical
changes can be less informative and usually appear later than biological changes.
Functional magnetic resonance imaging (MRI) has a potential to be a promising
technique for assessment of HCC response to therapy. In this review, we discuss
various functional MRI biomarkers that play an increasingly important role in
evaluation of HCC response after treatment.
PMID- 24356933
TI - Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal
junction adenocarcinoma.
AB - PURPOSE: The poor prognosis of gastroesophageal junction (GEJ) adenocarcinoma is
largely associated with metastasis. We here report the first study to investigate
the expression of epithelial-mesenchymal transition (EMT) markers Snail1 and E
cadherin in GEJ adenocarcinoma. METHODS: Snail1 and E-cadherin were detected by
immunohistochemistry in a cohort of 128 patients with surgically resected GEJ
adenocarcinoma. We assessed the pathologic and prognostic relevance in all
patients and within clinically different preserved E-cadherin and reduced E
cadherin-expressing sub-groups. RESULTS: Immunoreactivity for Snail1 and E
cadherin was positive in 68 and 43 % of tumors, respectively. Snail1-positive
tumors had more frequent lymph node metastasis and advanced tumor stage. E
cadherin expression was highly associated with histological differentiation,
tumor size, advanced stage, presence of lymph node metastasis and distant
metastasis. Patients with positive E-cadherin expression or negative Snail1
expression had significantly favorable overall survival rate. In E-cadherin
preserved tumors, the expression of Snail1 was related to lymph node metastasis,
advanced stage and poor patient outcome. However, Snail1 expression had no
statistically significant relationship with clinicopathologic parameters or
prognosis in the reduced E-cadherin-expressing sub-group. Multivariate survival
analysis identified that tumor stage [hazard ratio (HR) 2.440; 95 % confidence
interval (CI) 1.216-4.896; P = 0.012], lymph node metastasis (HR 2.404; 95 % CI
1.188-4.867; P = 0.015) and gender (HR 3.244; 95 % CI 1.568-6.714; P = 0.002)
were independent prognostic markers for overall survival. CONCLUSIONS: Snail1 may
act more critically in E-cadherin-positive tumors. Evaluation of Snail1 and E
cadherin in GEJ adenocarcinoma may help in assessing malignant properties and
stratifying patients.
PMID- 24356934
TI - Characterization of mechanism involved in acquired resistance to sorafenib in a
mouse renal cell cancer RenCa model.
AB - PURPOSE: The objective of this study was to investigate the mechanism mediating
the acquisition of a resistant phenotype to sorafenib in renal cell carcinoma
(RCC). METHODS: A parental mouse RCC cell line, RenCa (RenCa/P), was continuously
exposed to increasing doses of sorafenib, and a cell line resistant to sorafenib
(RenCa/R), showing an approximately sixfold higher IC(50) than that of RenCa/P,
was established. Changes in the expression of several molecules in these cell
lines following sorafenib treatment were evaluated by western blotting, and the
effects of sorafenib treatment on the in vivo growth patterns were compared.
RESULTS: There were no significant differences in sensitivities to potential
agents against RCC between RenCa/P and RenCa/R. Among several apoptosis-related
proteins, the expression of clusterin in RenCa/R was significantly greater than
that in RenCa/P. Following treatment with sorafenib, the expression level of
phosphorylated p44/42 mitogen-activated protein kinase (MAPK) in RenCa/P, but not
that in RenCa/R, was significantly decreased. Furthermore, additional treatment
with a specific inhibitor of the MAPK signaling pathway significantly increased
the sensitivity of RenCa/R to sorafenib, but not that of RenCa/P. There was no
significant difference between the in vivo growth patterns of RenCa/P and RenCa/R
in mice without sorafenib treatment; however, the growth inhibitory effect of
sorafenib on the RenCa/P tumor was significantly greater than that on the RenCa/R
tumor. CONCLUSIONS: These findings suggest that the upregulation of clusterin and
continuous activation of the MAPK pathway during sorafenib treatment may be
involved in the acquisition of a resistance to sorafenib in RCC.
PMID- 24356935
TI - Sulfated glycosaminoglycans support osteoblast functions and concurrently
suppress osteoclasts.
AB - In order to improve bone regeneration, development and evaluation of new adaptive
biomaterials is warranted. Glycosaminoglycans (GAGs) such as hyaluronan (HA) and
chondroitin sulfate (CS) are major extracellular matrix (ECM) components of bone,
and display osteogenic properties that are potentially useful for biomaterial
applications. Using native and synthetic sulfate-modified GAGs, we manufactured
artificial collagen/GAG ECM (aECMs) coatings, and evaluated how the presence of
GAGs and their degree of sulfation affects the differentiation of murine
mesenchymal stem cells to osteoblasts (OB) cultivated on these aECMs. GAG
sulfation regulated osteogenesis at all key steps of OB development. Adhesion,
but not migration, was diminished by 50% (P < 0.001). Proliferation and metabolic
activity were slightly (P < 0.05) and cell death events strongly (P < 0.001) down
regulated due to a switch from proliferative to matrix synthesis state. When
exposed to sulfated GAGs, OB marker genes, such as alkaline phosphatase,
osteoprotegerin (OPG), and osteocalcin increased by up to 28-fold (P < 0.05) and
calcium deposition up to 4-fold (P < 0.05). Furthermore, GAG treatment of OBs
suppressed their ability to support osteoclast (OC) differentiation and
resorption. In conclusion, GAG sulfation controls bone cell homeostasis by
concurrently promoting osteogenesis and suppressing their paracrine support of OC
functions, thus displaying a favorable profile on bone remodeling. Whether these
cellular properties translate into improved bone regeneration needs to be
validated in vivo.
PMID- 24356936
TI - Luminescent iron clusters in solution.
AB - Metal clusters, composed of a few atoms at the core, exhibit unique properties
and have potential applications. Although atomically precise clusters of noble
metals have been synthesized, analogous systems of reactive metals, such as iron,
have not been realized in solution due to high reactivity. Here we report the
synthesis and characterization of novel iron clusters in the hemoglobin matrix
that are highly luminescent (quantum yield 10% at 565 nm). The super-paramagnetic
iron clusters, after successful ligand exchange from protein and phase transfer
from water to chloroform using tri-octylphosphineoxide (TOPO), were detected as
[Fe10(TOPO)3(H2O)3](+), [Fe13(TOPO)2(H2O)](+) and [Fe8(TOPO)(H2O)2](+) by mass
spectrometry. This study lays the groundwork for exploiting unique properties of
soluble iron clusters.
PMID- 24356937
TI - Heart rate is associated with increased risk of major cardiovascular events,
cardiovascular and all-cause death in patients with stable chronic cardiovascular
disease: an analysis of ONTARGET/TRANSCEND.
AB - AIMS: Heart rate was proposed as an emergent cardiovascular (CV) risk factor.
Previous studies have shown associations between increased heart rate and CV risk
in various populations. We aimed to evaluate the prognostic relevance of heart
rate in a large contemporaneous medically optimized cohort of patients with
stable chronic CV disease. METHODS AND RESULTS: In a post hoc analysis of the
ONTARGET/TRANSCEND trials, we evaluated associations between baseline and average
heart rate in trial with CV risk in 31, 531 patients followed for a median of 5
years. The primary outcome, major vascular events (MVE), was a composite of CV
death, myocardial infarction (MI), stroke, and congestive heart failure (CHF).
Pre-specified secondary outcomes included all-cause death and the individual
components of the primary outcome. Associations between heart rate and outcomes
were computed with heart rate as a continuous variable, baseline heart rate >70
vs <= 70 bpm, and across heart rate quintiles, adjusting for other markers of
risk, beta-blocker and non-dihydropyridine calcium channel blocker use. For each
10 bpm increase in baseline and average heart rate, we observed a significant
increase in risk of MVE, CV death, CHF and all-cause death. There was a
continuous relationship between MVE and baseline and, more importantly, average
in-trial heart rate, with no observed threshold. MVE, CV death, stroke, CHF, and
all-cause death increased across heart rate quintiles. There was no association
between MI and HR. Results were consistent in clinically relevant subgroups.
There were modest but significant improvements in C-statistic and in statistical
measures of model calibration for models that included heart rate for MVE, CV
death, CHF and all-cause death. CONCLUSIONS: This large study examined and
quantitated associations between heart rate and CV events in a contemporary
medically optimized population with stable CV disease. Resting and, in
particular, in-trial average heart rate are independently associated with
significant increases in CV events and all-cause death.
PMID- 24356938
TI - Percutaneous closure of a gigantic patent ductus arteriosus (PDA) with pulmonary
hypertension with an atrial septal defect occluder in a 35-year-old woman.
PMID- 24356939
TI - Transcriptome-based functional classifiers for direct immunotoxicity.
AB - Current screening methods for direct immunotoxic chemicals are mainly based on
general toxicity studies with rodents. The present study aimed to identify
transcriptome-based functional classifiers that can eventually be exploited for
the development of in vitro screening assays for direct immunotoxicity. To this
end, a toxicogenomics approach was applied in which gene expression changes in
human Jurkat lymphoblastic T cells were investigated in response to a wide range
of compounds, including direct immunotoxicants, immunosuppressive drugs, and non
immunotoxic control chemicals. On the basis of DNA microarray data previously
obtained by the exposure of Jurkat cells to 31 test compounds (Shao et al. in
Toxicol Sci 135(2):328-346, 2013), we identified a set of 93 genes, of which 80
were significantly regulated (|numerical ratio| >=1.62) by at least three
compounds and the other 13 genes were significantly regulated by either one
single compound or compound class. A total of 28 most differentially regulated
genes were selected for qRT-PCR verification using a training set of 44 compounds
consisting of the above-mentioned 31 compounds (23 immunotoxic and 8 non
immunotoxic) and 13 additional immunotoxicants. Good correlation between the
results of microarray and qRT-PCR (Pearson's correlation, R >= 0.69) was found
for 27 out of the 28 genes. Redundancy analysis of these 27 potential classifiers
led to a final set of 25 genes. To assess the performance of these genes, Jurkat
cells were exposed to 20 additional compounds (external verification set)
followed by qRT-PCR. The classifier set of 25 genes gave a good performance in
the external verification: accuracy 85 %, true positive rate (sensitivity) 88 %,
and true negative rate (specificity) 67 %. Furthermore, on the basis of the gene
ontology annotation of the 25 classifier genes, the immunotoxicants examined in
this study could be categorized into distinct functional subclasses. In
conclusion, we have identified and validated classifier genes that can be used
for the development of an in vitro assay for the identification and initial
characterization of hazards for direct immunotoxicity of chemicals and drugs.
This assay promises to complement animal-free toxicity testing approaches within
the field of direct immunotoxicity.
PMID- 24356940
TI - Synthesis of the pluramycins 2: total synthesis and structure assignment of
saptomycin B.
AB - A concise, highly convergent total synthesis of saptomycin B, a member of the
pluramycin class of antitumor antibiotics, is reported. The target compound was
assembled from four building blocks (a tricyclic platform, two sugars, and an
alkynal) in 15% yield through 10 synthetic operations. The key steps included the
regioselective installation of two amino sugars (L-vancosamine and D
angolosamine) on the tricycle and the efficient construction of the tetracyclic
skeleton by an aldol reaction followed by formation of the pyranone. The unknown
configuration at C14 was assigned as R.
PMID- 24356941
TI - Ab initio protein folding simulations using atomic burials as informational
intermediates between sequence and structure.
AB - The three-dimensional structure of proteins is determined by their linear amino
acid sequences but decipherment of the underlying protein folding code has
remained elusive. Recent studies have suggested that burials, as expressed by
atomic distances to the molecular center, are sufficiently informative for
structural determination while potentially obtainable from sequences. Here we
provide direct evidence for this distinctive role of burials in the folding code,
demonstrating that burial propensities estimated from local sequence can indeed
be used to fold globular proteins in ab initio simulations. We have used a
statistical scheme based on a Hidden Markov Model (HMM) to classify all heavy
atoms of a protein into a small number of burial atomic types depending on
sequence context. Molecular dynamics simulations were then performed with a
potential that forces all atoms of each type towards their predicted burial
level, while simple geometric constraints were imposed on covalent structure and
hydrogen bond formation. The correct folded conformation was obtained and
distinguished in simulations that started from extended chains for a selection of
structures comprising all three folding classes and high burial prediction
quality. These results demonstrate that atomic burials can act as informational
intermediates between sequence and structure, providing a new conceptual
framework for improving structural prediction and understanding the fundamentals
of protein folding.
PMID- 24356942
TI - Biomechanics of the posterior eye: a critical role in health and disease.
AB - The posterior eye is a complex biomechanical structure. Delicate neural and
vascular tissues of the retina, choroid, and optic nerve head that are critical
for visual function are subjected to mechanical loading from intraocular
pressure, intraocular and extraorbital muscles, and external forces on the eye.
The surrounding sclera serves to counteract excessive deformation from these
forces and thus to create a stable biomechanical environment for the ocular
tissues. Additionally, the eye is a dynamic structure with connective tissue
remodeling occurring as a result of aging and pathologies such as glaucoma and
myopia. The material properties of these tissues and the distribution of stresses
and strains in the posterior eye is an area of active research, relying on a
combination of computational modeling, imaging, and biomechanical measurement
approaches. Investigators are recognizing the increasing importance of the role
of the collagen microstructure in these material properties and are undertaking
microstructural measurements to drive microstructurally-informed models of ocular
biomechanics. Here, we review notable findings and the consensus understanding on
the biomechanics and microstructure of the posterior eye. Results from
computational and numerical modeling studies and mechanical testing of ocular
tissue are discussed. We conclude with some speculation as to future trends in
this field.
PMID- 24356943
TI - RhoBTB2 gene in breast cancer is silenced by promoter methylation.
AB - Mutation analysis in breast cancer has failed to explain the inactivation of
RhoBTB2, a candidate breast cancer tumor suppressor gene on chromosome 8p. Some
breast cancer-related genes in this region become inactivated by
hypermethylation, and hypermethylation of RhoBTB2 abrogates its expression in
bladder cancers. The aim of the present study was to determine whether RhoBTB2
was silenced by methylation in breast cancer. Nested methylation-specific PCR
(nMSP) and quantitative reverse transcription PCR were used to analyze the
methylation status and mRNA levels of RhoBTB2 in 50 paired breast cancer and
normal tissues and the results were correlated with clinicopathological
characteristics. Promoter methylation and the downregulation of RhoBTB2 mRNA was
observed in tumor tissues (P<0.001). mRNA levels were decreased in samples with
methylation (chi2 = 15.751, P<0.001). RhoBTB2 methylation was observed
preferentially in progesterone receptor (PR)-negative samples (P<0.05). The
results demonstrated that aberrant methylation of RhoBTB2 may be responsible for
the suppression of RhoBTB2 mRNA expression in breast cancer, a significant event
during the genesis of breast cancer that correlated with PR status.
PMID- 24356944
TI - Endovascular treatment with primary stenting of inferior cava vein torsion
following orthotopic liver transplantation with modified piggyback technique.
AB - PURPOSE: This study was undertaken to evaluate primary stenting in patients with
inferior vena cava torsion after orthotopic liver transplantation performed with
modified piggyback technique. MATERIALS AND METHODS: From November 2003 to
October 2010, six patients developed clinical, laboratory and imaging findings
suggestive of caval stenosis, after a mean period of 21 days from an orthotopic
liver transplantation performed with modified piggyback technique. Vena
cavography showed stenosis due to torsion of the inferior vena cava at the
anastomoses and a significant caval venous pressure gradient. All patients were
treated with primary stenting followed by in-stent angioplasty in three cases.
RESULTS: In all patients, the stents were successfully positioned at the caval
anastomosis and the venous gradient pressure fell from a mean value of 10 to 2
mmHg. Signs and symptoms resolved in all six patients. One patient died 3 months
after stent placement due to biliary complications. No evidence of recurrence or
complications was noted during the follow-up (mean 49 months). CONCLUSIONS:
Primary stenting of inferior vena cava stenosis due to torsion of the anastomoses
in patients receiving orthotopic liver transplantation with modified piggyback
technique is a safe, effective and durable treatment.
PMID- 24356945
TI - Ionising radiation awareness among resident doctors, interns, and radiographers
in a university hospital emergency department.
AB - PURPOSE: In emergency medicine practice, radiological investigations relying on
ionising radiation are increasingly used to diagnose a wide range of diseases and
injuries. The aim of this study was to investigate the knowledge of radiation
exposure doses and risks among interns, resident doctors, and radiographers.
MATERIALS AND METHODS: A questionnaire, consisting of 14 questions in multiple
choice format, was distributed to 300 participants (100 interns, 100
radiographers, 100 resident doctors) working in the emergency department. The
participants were asked to estimate the radiation dose that patients received
during the different radiological procedures. The questionnaire was designed to
determine the participants' knowledge about radiation-related hazards. RESULTS:
None of the radiation doses delivered by the imaging modalities was 100%
correctly estimated. A total of 41.4% of all participants and 46.3% of resident
doctors underestimated the radiation doses. The frequency of answers
underestimating doses was found to be significantly higher (p < 0.001). Resident
doctors, with a 39.4% correct answer rate, were found to be significantly less
knowledgeable when compared with the interns and radiographers (p = 0.003).
Emergency resident doctors had a statistically significantly higher rate of
correct answers for the lowest and highest radiation sources for a foetus when
compared with other groups (p = 0.001, p = 0.008). CONCLUSION: Our study showed
that the resident doctors', interns', and radiographers' knowledge of radiation
exposure from radiological investigations and the associated risks was poor. This
result could imply that we are not aware of the radiation risks, and we are
inattentive in informing our patients about the radiation exposure related to the
different imaging modalities.
PMID- 24356946
TI - Diethyl fluoronitromethylphosphonate: synthesis and application in nucleophilic
fluoroalkyl additions.
AB - Diethyl fluoronitromethylphosphonate (3), a previously unknown compound, was
synthesized by electrophilic fluorination of diethyl nitromethylphosphonate with
Selectfluor. Base-induced decomposition of 3 was studied by NMR spectroscopy,
which identified diethyl fluorophosphate and fluoronitromethane as the main
decomposition products. C-H acidities [pK(a) values in dimethyl sulfoxide (DMSO)]
of 3, 1-fluoro-1-phenylsulfonylmethanephosphonate (1; McCarthy's reagent),
tetraethyl fluoromethylenebisphosphonate (2), and some nonfluorinated
phosphonates were computed, and a good correlation between calculated and
experimental pK(a) values was found. The calculated C-H acidities increased in
the sequence 2<1<3. Diethyl fluoronitromethylphosphonate (3) was applied in the
Horner-Wadsworth-Emmons reaction with aldehydes and trifluoromethyl ketones to
provide new 1-fluoro-1-nitroalkenes with good to high stereoselectivities.
Alkylation of 3 was successful only with iodomethane, however, conjugate
additions of 3 to Michael acceptors such as alpha,beta-unsaturated carbonyl
compounds, sulfones, and nitro compounds allowed access to variously modified
diethyl 1-fluoro-1-nitrophosphonates.
PMID- 24356947
TI - Rebound sex: Sexual motives and behaviors following a relationship breakup.
AB - The present study used a longitudinal, online diary method to examine
trajectories of psychological recovery and sexual experience following a romantic
relationship breakup among 170 undergraduate students. Consistent with popular
beliefs about rebound and revenge sex, having sex to cope with distress and to
get over or get back at the ex-partner were elevated immediately following the
breakup and then declined over time, as did the probability of having sex with a
new partner. Also consistent with popular lore, those who were "dumped" by their
partners were more distressed and angry and more likely to have sex to cope and
to get back at or get over their ex-partner. Finally, individuals who reported
having sex to cope with negative feelings or to get over their ex-partner at the
beginning of the study were more likely to have sex with a stranger and to
continue having sex with new partners over time. Results were discussed in terms
of widely held but largely untested beliefs about rebound and revenge sex.
PMID- 24356948
TI - Sociosexual orientation and 2D:4D ratios in women: Relationship to men's
desirability ratings as a long-term pair bond.
AB - The current study examined whether men's ratings of women's desirability as a
long-term pairbond, based on static photographs, were related to the women's
second-to-fourth digit (2D:4D) ratio and their sexual attitudes and behavior. The
2D:4D ratio was measured in 164 women and facial photographs were taken of 55 of
these women. All women completed the Sociosexual Orientation Inventory (SOI).
Male participants (n = 89), masked to this information, rated the 55 female
participants on their desirability as a long-term sexual partner, specifically
along dimensions of faithfulness, youthfulness, and attractiveness. Ten
independent judges rated women's photographed faces on masculinity. Results
indicated a significant negative relationship between women's SOI scores and
men's faithfulness ratings (more unrestricted sociosexuality was associated with
lower faithfulness ratings). There was also a significant positive relationship
between right (but not left) 2D:4D ratio and faithfulness ratings (women with
female-like ratios were rated as being more faithful). The SOI scores of the
women were not related to 2D:4D ratios. These results suggest that the potential
for sexual infidelity can be gleaned from static facial cues.
PMID- 24356949
TI - Sex and cultural differences in spatial performance between Japanese and North
Americans.
AB - Previous studies have suggested that Asians perform better than North Americans
on spatial tasks but show smaller sex differences. In this study, we evaluated
the relationship between long-term experience with a pictorial written language
and spatial performance. It was hypothesized that native Japanese Kanji (a
complex pictorial written language) educated adults would show smaller sex
differences on spatial tasks than Japanese Americans or North Americans without
Kanji education. A total of 80 young healthy participants (20 native Japanese
speakers, 20 Japanese Americans-non Japanese speaking, and 40 North Americans-non
Japanese speaking) completed the Rey Complex Figure Test (RCFT), the Mental
Rotations Test (MRT), and customized 2D and 3D spatial object location memory
tests. As predicted, main effects revealed men performed better on the MRT and
RCFT and women performed better on the spatial object location memory tests.
Also, as predicted, native Japanese performed better on all tests than the other
groups. In contrast to the other groups, native Japanese showed a decreased
magnitude of sex differences on aspects of the RCFT (immediate and delayed
recall) and no significant sex difference on the efficiency of the strategy used
to copy and encode the RCFT figure. This study lends support to the idea that
intensive experience over time with a pictorial written language (i.e., Japanese
Kanji) may contribute to increased spatial performance on some spatial tasks as
well as diminish sex differences in performance on tasks that most resemble
Kanji.
PMID- 24356950
TI - Effect of mechanical strain on the collagen VI pericellular matrix in anterior
cruciate ligament fibroblasts.
AB - Cell-extracellular matrix interaction plays a major role in maintaining the
structural integrity of connective tissues and sensing changes in the
biomechanical environment of cells. Collagen VI is a widely expressed non
fibrillar collagen, which regulates tissues homeostasis. The objective of the
present investigation was to extend our understanding of the role of collagen VI
in human ACL. This study shows that collagen VI is associated both in vivo and in
vitro to the cell membrane of knee ACL fibroblasts, contributing to the
constitution of a microfibrillar pericellular matrix. In cultured cells the
localization of collagen VI at the cell surface correlated with the expression of
NG2 proteoglycan, a major collagen VI receptor. The treatment of ACL fibroblasts
with anti-NG2 antibody abolished the localization of collagen VI indicating that
collagen VI pericellular matrix organization in ACL fibroblasts is mainly
mediated by NG2 proteoglycan. In vitro mechanical strain injury dramatically
reduced the NG2 proteoglycan protein level, impaired the association of collagen
VI to the cell surface, and promoted cell cycle withdrawal. Our data suggest that
the injury-induced alteration of specific cell-ECM interactions may lead to a
defective fibroblast self-renewal and contribute to the poor regenerative ability
of ACL fibroblasts.
PMID- 24356951
TI - Population impact of increased body mass index and attenuated beta-cell function
on worsening of glucose metabolism in subjects with normal glucose tolerance: a
pilot study.
AB - The population attributable fraction (PAF) of risk factors for the worsening of
glucose metabolism in subjects with normal glucose tolerance (NGT) has not been
calculated. Our aim was to obtain the PAF of increased body mass index (BMI) and
attenuated beta-cell function (BCF) on worsening of glucose metabolism in
subjects with NGT. We longitudinally analyzed 604 Japanese adults. The follow-up
glucose tolerance status was determined 3.7 years later: 430 participants
remained in the NGT category and 102 had progressed to impaired fasting glucose,
67 to impaired glucose tolerance, and 5 to diabetes mellitus. A product of
ISIMatsuda and Stumvoll-1, i.e., oral disposition index (DIO), was used as a
measure of BCF. The optimal cutoff baseline BMI and DIO values for the prediction
of the worsening of glucose metabolism were > 23.1 and < 7.299 kg/m(2),
respectively. Isolated increased BMI (iBMIHIGH), isolated low DI (iDIOLOW), and
"BMIHIGH and DIOLOW (BMIHIGH/DIOLOW)" were all independently related to the
worsening, and the PAF values (95 % CI) for worsening due to iBMIHIGH, iDIOLOW,
and BMIHIGH/DIOLOW were 12.9 (3.2-18.4) %, 10.9 (5.0-13.9) %, and 31.4 (22.7
36.3) %, respectively. As much as 55 % of the worsening of glucose metabolism in
the NGT subjects was attributable to increased BMI and/or attenuated BCF. The
optimal cutoff for BMI was as low as 23.1 kg/m(2) in this population. We believe
that these data should form the basis of future public health strategies for the
prevention of diabetes in Japan.
PMID- 24356952
TI - Vitamin D deficiency, serum leptin and osteoprotegerin levels in older diabetic
patients: an input to new research avenues.
AB - The aim of this study was to assess the effects of single oral bolus of 300,000
IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic
patients. This study is a Phase IV, randomized, double-blind, placebo-controlled,
monocenter clinical trial. Thirty patients, 60 years or older, with type 2
diabetes mellitus, and diabetic foot complications, were enrolled and monitored
for 24 weeks: 14 were treated with Vitamin D3 and 16 with placebo. Parameters
including glucose, adiponectin, leptin, osteoprotegerin (OPG), 25-hydroxyvitamin
D [25(OH)D], beta-CrossLaps, osteocalcin, bone-specific isoenzyme of alkaline
phosphatase, tumor necrosis factor-alpha and parathyroid hormone were measured at
screening and baseline and 12 and 24 weeks after treatment. Analysis of
covariance was used to compare treatment groups. Analysis of the data detected a
significant increase in 25(OH)D serum levels both at 12 and 24 weeks with respect
to baseline values only in the treated patients. Significant variations with
respect to baseline values were noted in OPG (P = 0.0085) and in leptin (P =
0.0442) levels: these were lower in the placebo group at week 24 but higher in
the treated group. Vitamin D3 supplementation significantly increased serum
leptin and OPG levels. Further, large-scale clinical trials are warranted to
confirm these results.
PMID- 24356953
TI - A missense mutation in Rev7 disrupts formation of Polzeta, impairing mouse
development and repair of genotoxic agent-induced DNA lesions.
AB - Repro22 is a mutant mouse produced via N-ethyl-N-nitrosourea-induced mutagenesis
that shows sterility with germ cell depletion caused by defective proliferation
of primordial germ cells, decreased body weight, and partial lethality during
embryonic development. Using a positional cloning strategy, we identified a
missense mutation in Rev7/Mad2l2 (Rev7(C70R)) and confirmed that the mutation is
the cause of the defects in repro22 mice through transgenic rescue with normal
Rev7. Rev7/Mad2l2 encodes a subunit of DNA polymerase zeta (Polzeta), 1 of 10
translesion DNA synthesis polymerases known in mammals. The mutant REV7 did not
interact with REV3, the catalytic subunit of Polzeta. Rev7(C70R/C70R) cells
showed decreased proliferation, increased apoptosis, and arrest in S phase with
extensive gammaH2AX foci in nuclei that indicated accumulation of DNA damage
after treatment with the genotoxic agent mitomycin C. The Rev7(C70R) mutation
does not affect the mitotic spindle assembly checkpoint. These results
demonstrated that Rev7 is essential in resolving the replication stalls caused by
DNA damage during S phase. We concluded that Rev7 is required for primordial germ
cell proliferation and embryonic viability and development through the
translesion DNA synthesis activity of Polzeta preserving DNA integrity during
cell proliferation, which is required in highly proliferating embryonic cells.
PMID- 24356954
TI - Role of stearoyl-CoA desaturase-1 in skin integrity and whole body energy
balance.
AB - The skin is the single largest organ in humans, serving as a major barrier to
infection, water loss, and abrasion. The functional diversity of skin requires
the synthesis of large amounts of lipids, such as triglycerides, wax esters,
squalene, ceramides, free cholesterol, free fatty acids, and cholesterol and
retinyl esters. Some of these lipids are used as cell membrane components,
signaling molecules, and a source of energy. An important class of lipid
metabolism enzymes expressed in skin is the Delta(9)-desaturases, which catalyze
the synthesis in Delta(9)-monounsaturated lipids, primarily oleoyl-CoA (18:1n-9)
and palmitoyl-CoA (16:1n-7), the major monounsaturated fatty acids in cutaneous
lipids. Mice with a deletion of the Delta(9)-desaturase-1 isoform (SCD1) either
globally (Scd1(-/-)) or specifically in the skin (skin-specific Scd1-knockout;
SKO) present with marked changes in cutaneous lipids and skin integrity.
Interestingly, these mice also exhibit increased whole body energy expenditure,
protection against diet-induced adiposity, hepatic steatosis, and glucose
intolerance. The increased energy expenditure in skin-specific Scd1-knockout
(SKO) mice is a surprising phenotype, as it links cutaneous lipid homeostasis
with whole body energy balance. This minireview summarizes the role of skin SCD1
in regulating skin integrity and whole body energy homeostasis and offers a
discussion of potential pathways that may connect these seemingly disparate
phenotypes.
PMID- 24356955
TI - The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating
enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the
ventral nerve cord of Caenorhabditis elegans.
AB - Ubiquitin-mediated endocytosis and degradation of glutamate receptors controls
their synaptic abundance and is implicated in modulating synaptic strength. The
deubiquitinating enzymes (DUBs) that function in the nervous system are beginning
to be defined, but the mechanisms that control DUB activity in vivo are
understood poorly. We found previously that the DUB USP-46 deubiquitinates the
Caenorhabditis elegans glutamate receptor GLR-1 and prevents its degradation in
the lysosome. The WD40-repeat (WDR) proteins WDR20 and WDR48/UAF1 have been shown
to bind to USP46 and stimulate its catalytic activity in other systems. Here we
identify the C. elegans homologs of these WDR proteins and show that C. elegans
WDR-20 and WDR-48 can bind and stimulate USP-46 catalytic activity in vitro.
Overexpression of these activator proteins in vivo increases the abundance of GLR
1 in the ventral nerve cord, and this effect is further enhanced by coexpression
of USP-46. Biochemical characterization indicates that this increase in GLR-1
abundance correlates with decreased levels of ubiquitin-GLR-1 conjugates,
suggesting that WDR-20, WDR-48, and USP-46 function together to deubiquitinate
and stabilize GLR-1 in neurons. Overexpression of WDR-20 and WDR-48 results in
alterations in locomotion behavior consistent with increased glutamatergic
signaling, and this effect is blocked in usp-46 loss-of-function mutants.
Conversely, wdr-20 and wdr-48 loss-of-function mutants exhibit changes in
locomotion behavior that are consistent with decreased glutamatergic signaling.
We propose that WDR-20 and WDR-48 form a complex with USP-46 and stimulate the
DUB to deubiquitinate and stabilize GLR-1 in vivo.
PMID- 24356956
TI - Endothelial lineage differentiation from induced pluripotent stem cells is
regulated by microRNA-21 and transforming growth factor beta2 (TGF-beta2)
pathways.
AB - Finding a suitable cell source for endothelial cells (ECs) for cardiovascular
regeneration is a challenging issue for regenerative medicine. In this paper, we
describe a novel mechanism regulating induced pluripotent stem cells (iPSC)
differentiation into ECs, with a particular focus on miRNAs and their targets. We
first established a protocol using collagen IV and VEGF to drive the functional
differentiation of iPSCs into ECs and compared the miRNA signature of
differentiated and undifferentiated cells. Among the miRNAs overrepresented in
differentiated cells, we focused on microRNA-21 (miR-21) and studied its role in
iPSC differentiation. Overexpression of miR-21 in predifferentiated iPSCs induced
EC marker up-regulation and in vitro and in vivo capillary formation;
accordingly, inhibition of miR-21 produced the opposite effects. Importantly, miR
21 overexpression increased TGF-beta2 mRNA and secreted protein level, consistent
with the strong up-regulation of TGF-beta2 during iPSC differentiation. Indeed,
treatment of iPSCs with TGFbeta-2 induced EC marker expression and in vitro tube
formation. Inhibition of SMAD3, a downstream effector of TGFbeta-2, strongly
decreased VE-cadherin expression. Furthermore, TGFbeta-2 neutralization and
knockdown inhibited miR-21-induced EC marker expression. Finally, we confirmed
the PTEN/Akt pathway as a direct target of miR-21, and we showed that PTEN
knockdown is required for miR-21-mediated endothelial differentiation. In
conclusion, we elucidated a novel signaling pathway that promotes the
differentiation of iPSC into functional ECs suitable for regenerative medicine
applications.
PMID- 24356957
TI - Characterization of the deubiquitinating activity of USP19 and its role in
endoplasmic reticulum-associated degradation.
AB - Deubiquitinating enzymes (DUBs) regulate various cellular processes ranging from
protein degradation to cellular signaling. USP19, the only DUB containing a
carboxyl-terminal transmembrane domain, was proposed to function in endoplasmic
reticulum-associated degradation (ERAD). Here we characterize the function and
regulation of USP19. We identify Hsp90 as a specific partner that binds the
catalytic domain of USP19 to promote substrate association. Intriguingly,
although overexpressed USP19 interacts with Derlin-1 and other ERAD machinery
factors in the membrane, endogenous USP19 is mostly in the cytosol where it binds
Hsp90. Accordingly, we detect neither interaction of endogenous USP19 with Derlin
1 nor significant effect on ERAD by USP19 depletion. The USP19 transmembrane
domain appears to be partially stabilized in the cytosol by an interaction with
its own catalytic domain, resulting in auto-inhibition of its deubiquitinating
activity. These results clarify the role of USP19 in ERAD and suggest a novel DUB
regulation that involves chaperone association and membrane integration.
Moreover, our study indicates that the localization of tail-anchored membrane
proteins can be subject to regulation in cells.
PMID- 24356958
TI - The fibrinogen-binding M1 protein reduces pharyngeal cell adherence and
colonization phenotypes of M1T1 group A Streptococcus.
AB - Group A Streptococcus (GAS) is a leading human pathogen producing a diverse array
of infections from simple pharyngitis ("strep throat") to invasive conditions,
including necrotizing fasciitis and toxic shock syndrome. The surface-anchored
GAS M1 protein is a classical virulence factor that promotes phagocyte resistance
and exaggerated inflammation by binding host fibrinogen (Fg) to form
supramolecular networks. In this study, we used a virulent WT M1T1 GAS strain and
its isogenic M1-deficient mutant to examine the role of M1-Fg binding in a
proximal step in GAS infection-interaction with the pharyngeal epithelium.
Expression of the M1 protein reduced GAS adherence to human pharyngeal
keratinocytes by 2-fold, and this difference was increased to 4-fold in the
presence of Fg. In stationary phase, surface M1 protein cleavage by the GAS
cysteine protease SpeB eliminated Fg binding and relieved its inhibitory effect
on GAS pharyngeal cell adherence. In a mouse model of GAS colonization of nasal
associated lymphoid tissue, M1 protein expression was associated with an average
6-fold decreased GAS recovery in isogenic strain competition assays. Thus, GAS M1
protein-Fg binding reduces GAS pharyngeal cell adherence and colonization in a
fashion that is counterbalanced by SpeB. Inactivation of SpeB during the shift to
invasive GAS disease allows M1-Fg binding, increasing pathogen phagocyte
resistance and proinflammatory activities.
PMID- 24356959
TI - Defects in mitochondrial clearance predispose human monocytes to interleukin
1beta hypersecretion.
AB - Most hereditary periodic fever syndromes are mediated by deregulated IL-1beta
secretion. The generation of mature IL-1beta requires two signals: one that
induces synthesis of inflammasome components and substrates and a second that
activates inflammasomes. The mechanisms that mediate autoinflammation in
mevalonate kinase deficiency, a periodic fever disease characterized by a block
in isoprenoid biosynthesis, are poorly understood. In studying the effects of
isoprenoid shortage on IL-1 beta generation, we identified a new inflammasome
activation signal that originates from defects in autophagy. We find that
hypersecretion of IL-1beta and IL-18 requires reactive oxygen species and is
associated with an oxidized redox status of monocytes but not lymphocytes. IL
1beta hypersecretion by monocytes involves decreased mitochondrial stability,
release of mitochondrial content into the cytosol and attenuated autophagosomal
degradation. Defective autophagy, as established by ATG7 knockdown, results in
prolonged cytosolic retention of damaged mitochondria and increased IL-1beta
secretion. Finally, activation of autophagy in healthy but not mevalonate kinase
deficiency patient cells reduces IL-1beta secretion. Together, these results
indicate that defective autophagy can prime monocytes for mitochondria-mediated
NLRP3 inflammasome activation, thereby contributing to hypersecretion of IL-1beta
in mevalonate kinase deficiency.
PMID- 24356960
TI - Chronic high glucose and pyruvate levels differentially affect mitochondrial
bioenergetics and fuel-stimulated insulin secretion from clonal INS-1 832/13
cells.
AB - Glucotoxicity in pancreatic beta-cells is a well established pathogenetic process
in type 2 diabetes. It has been suggested that metabolism-derived reactive oxygen
species perturb the beta-cell transcriptional machinery. Less is known about
altered mitochondrial function in this condition. We used INS-1 832/13 cells
cultured for 48 h in 2.8 mm glucose (low-G), 16.7 mm glucose (high-G), or 2.8 mm
glucose plus 13.9 mm pyruvate (high-P) to identify metabolic perturbations. High
G cells showed decreased responsiveness, relative to low-G cells, with respect to
mitochondrial membrane hyperpolarization, plasma membrane depolarization, and
insulin secretion, when stimulated acutely with 16.7 mm glucose or 10 mm
pyruvate. In contrast, high-P cells were functionally unimpaired, eliminating
chronic provision of saturating mitochondrial substrate as a cause of
glucotoxicity. Although cellular insulin content was depleted in high-G cells,
relative to low-G and high-P cells, cellular functions were largely recovered
following a further 24-h culture in low-G medium. After 2 h at 2.8 mm glucose,
high-G cells did not retain increased levels of glycolytic or TCA cycle
intermediates but nevertheless displayed increased glycolysis, increased
respiration, and an increased mitochondrial proton leak relative to low-G and
high-P cells. This notwithstanding, titration of low-G cells with low
protonophore concentrations, monitoring respiration and insulin secretion in
parallel, showed that the perturbed insulin secretion of high-G cells could not
be accounted for by increased proton leak. The present study supports the idea
that glucose-induced disturbances of stimulus-secretion coupling by
extramitochondrial metabolism upstream of pyruvate, rather than exhaustion from
metabolic overload, underlie glucotoxicity in insulin-producing cells.
PMID- 24356961
TI - GCN5-like protein 1 (GCN5L1) controls mitochondrial content through coordinated
regulation of mitochondrial biogenesis and mitophagy.
AB - Cellular mitochondrial content is governed by the competing processes of
organelle biogenesis and degradation. It is proposed that these programs are
tightly regulated to ensure that the cell maintains sufficient organelles to meet
its biosynthetic, energetic, and other homeostatic requirements. We recently
reported that GCN5L1, a putative nutrient-sensing regulator, controls
mitochondrial removal by autophagy. Here we show that genetic deletion of GCN5L1
has a direct positive effect on the expression and activity of Transcriptional
Factor EB (TFEB), which acts as a master regulator of autophagy. Surprisingly,
the induction of TFEB-mediated autophagy pathways does not diminish cellular
mitochondrial content, as its activity is countered by induction of the
mitochondrial biogenesis transcriptional co-activator PPARgamma coactivator
1alpha (PGC-1alpha). Concurrent induction of the TFEB and PGC-1alpha pathways
results in an increased mitochondrial turnover rate in GCN5L1(-/-) cells.
Finally, we show that genetic knockdown of either TFEB or PGC-1alpha leads to a
corresponding decrease in the expression of the other gene, indicating that these
proteins act coordinately, and in opposition, to maintain cellular mitochondrial
content in response to the modulation of nutrient-sensing signatures.
PMID- 24356963
TI - Tracing primordial protein evolution through structurally guided stepwise segment
elongation.
AB - The understanding of how primordial proteins emerged has been a fundamental and
longstanding issue in biology and biochemistry. For a better understanding of
primordial protein evolution, we synthesized an artificial protein on the basis
of an evolutionary hypothesis, segment-based elongation starting from an
autonomously foldable short peptide. A 10-residue protein, chignolin, the
smallest foldable polypeptide ever reported, was used as a structural support to
facilitate higher structural organization and gain-of-function in the development
of an artificial protein. Repetitive cycles of segment elongation and subsequent
phage display selection successfully produced a 25-residue protein, termed
AF.2A1, with nanomolar affinity against the Fc region of immunoglobulin G. AF.2A1
shows exquisite molecular recognition ability such that it can distinguish
conformational differences of the same molecule. The structure determined by NMR
measurements demonstrated that AF.2A1 forms a globular protein-like conformation
with the chignolin-derived beta-hairpin and a tryptophan-mediated hydrophobic
core. Using sequence analysis and a mutation study, we discovered that the
structural organization and gain-of-function emerged from the vicinity of the
chignolin segment, revealing that the structural support served as the core in
both structural and functional development. Here, we propose an evolutionary
model for primordial proteins in which a foldable segment serves as the evolving
core to facilitate structural and functional evolution. This study provides
insights into primordial protein evolution and also presents a novel methodology
for designing small sized proteins useful for industrial and pharmaceutical
applications.
PMID- 24356962
TI - Relationship between intracellular Na+ concentration and reduced Na+ affinity in
Na+,K+-ATPase mutants causing neurological disease.
AB - The neurological disorders familial hemiplegic migraine type 2 (FHM2),
alternating hemiplegia of childhood (AHC), and rapid-onset dystonia parkinsonism
(RDP) are caused by mutations of Na(+),K(+)-ATPase alpha2 and alpha3 isoforms,
expressed in glial and neuronal cells, respectively. Although these disorders are
distinct, they overlap in phenotypical presentation. Two Na(+),K(+)-ATPase
mutations, extending the C terminus by either 28 residues ("+28" mutation) or an
extra tyrosine ("+Y"), are associated with FHM2 and RDP, respectively. We
describe here functional consequences of these and other neurological disease
mutations as well as an extension of the C terminus only by a single alanine. The
dependence of the mutational effects on the specific alpha isoform in which the
mutation is introduced was furthermore studied. At the cellular level we have
characterized the C-terminal extension mutants and other mutants, addressing the
question to what extent they cause a change of the intracellular Na(+) and K(+)
concentrations ([Na(+)]i and [K(+)]i) in COS cells. C-terminal extension mutants
generally showed dramatically reduced Na(+) affinity without disturbance of K(+)
binding, as did other RDP mutants. No phosphorylation from ATP was observed for
the +28 mutation of alpha2 despite a high expression level. A significant rise of
[Na(+)]i and reduction of [K(+)]i was detected in cells expressing mutants with
reduced Na(+) affinity and did not require a concomitant reduction of the maximal
catalytic turnover rate or expression level. Moreover, two mutations that
increase Na(+) affinity were found to reduce [Na(+)]i. It is concluded that the
Na(+) affinity of the Na(+),K(+)-ATPase is an important determinant of [Na(+)]i.
PMID- 24356964
TI - The beta-prism lectin domain of Vibrio cholerae hemolysin promotes self-assembly
of the beta-pore-forming toxin by a carbohydrate-independent mechanism.
AB - Vibrio cholerae cytolysin/hemolysin (VCC) is an amphipathic 65-kDa beta-pore
forming toxin with a C-terminal beta-prism lectin domain. Because deletion or
point mutation of the lectin domain seriously compromises hemolytic activity, it
is thought that carbohydrate-dependent interactions play a critical role in
membrane targeting of VCC. To delineate the contributions of the cytolysin and
lectin domains in pore formation, we used wild-type VCC, 50-kDa VCC (VCC(50))
without the lectin domain, and mutant VCC(D617A) with no carbohydrate-binding
activity. VCC and its two variants with no carbohydrate-binding activity moved to
the erythrocyte stroma with apparent association constants on the order of 10(7)
M(-1). However, loss of the lectin domain severely reduced the efficiency of self
association of the VCC monomer with the beta-barrel heptamer in the synthetic
lipid bilayer from ~83 to 27%. Notably, inactivation of the carbohydrate-binding
activity by the D617A mutation marginally reduced oligomerization to ~77%.
Oligomerization of VCC(50) was temperature-insensitive; by contrast, VCC self
assembly increased with increasing temperature, suggesting that the process is
driven by entropy and opposed by enthalpy. Asialofetuin, the beta1-galactosyl
terminated glycoprotein inhibitor of VCC-induced hemolysis, promoted
oligomerization of 65-kDa VCC to a species that resembled the membrane-inserted
heptamer in stoichiometry and morphology but had reduced global amphipathicity.
In conclusion, we propose (i) that the beta-prism lectin domain facilitated toxin
assembly by producing entropy during relocation in the heptamer and (ii) that
glycoconjugates inhibited VCC by promoting its assembly to a water-soluble, less
amphipathic oligomer variant with reduced ability to penetrate the bilayer.
PMID- 24356965
TI - Characterization and structure of the vaccinia virus NF-kappaB antagonist A46.
AB - Successful vaccinia virus (VACV) replication in the host requires expression of
viral proteins that interfere with host immunity, such as antagonists of the
activation of the proinflammatory transcription factor NF-kappaB. Two such VACV
proteins are A46 and A52. A46 interacts with the Toll-like receptor/interleukin
1R (TIR) domain of Toll-like receptors and intracellular adaptors such as MAL
(MyD88 adapter-like), TRAM (TIR domain-containing adapter-inducing interferon
beta (TRIF)-related adaptor molecule), TRIF, and MyD88, whereas A52 binds to the
downstream signaling components TRAF6 and IRAK2. Here, we characterize A46
biochemically, determine by microscale thermophoresis binding constants for the
interaction of A46 with the TIR domains of MyD88 and MAL, and present the 2.0 A
resolution crystal structure of A46 residues 87-229. Full-length A46 behaves as a
tetramer; variants lacking the N-terminal 80 residues are dimeric. Nevertheless,
both bind to the Toll-like receptor domains of MAL and MyD88 with KD values in
the low MUm range. Like A52, A46 also shows a Bcl-2-like fold but with
biologically relevant differences from that of A52. Thus, A46 uses helices alpha4
and alpha6 to dimerize, compared with the alpha1-alpha6 face used by A52 and
other Bcl-2 like VACV proteins. Furthermore, the loop between A46 helices alpha4
alpha5 is flexible and shorter than in A52; there is also evidence for an
intramolecular disulfide bridge between consecutive cysteine residues. We used
molecular docking to propose how A46 interacts with the BB loop of the TRAM TIR
domain. Comparisons of A46 and A52 exemplify how subtle changes in viral proteins
with the same fold lead to crucial differences in biological activity.
PMID- 24356966
TI - The crystal structure of the streptococcal collagen-like protein 2 globular
domain from invasive M3-type group A Streptococcus shows significant similarity
to immunomodulatory HIV protein gp41.
AB - The arsenal of virulence factors deployed by streptococci includes streptococcal
collagen-like (Scl) proteins. These proteins, which are characterized by a
globular domain and a collagen-like domain, play key roles in host adhesion, host
immune defense evasion, and biofilm formation. In this work, we demonstrate that
the Scl2.3 protein is expressed on the surface of invasive M3-type strain MGAS315
of Streptococcus pyogenes. We report the crystal structure of Scl2.3 globular
domain, the first of any Scl. This structure shows a novel fold among collagen
trimerization domains of either bacterial or human origin. Despite there being
low sequence identity, we observed that Scl2.3 globular domain structurally
resembles the gp41 subunit of the envelope glycoprotein from human
immunodeficiency virus type 1, an essential subunit for viral fusion to human T
cells. We combined crystallographic data with modeling and molecular dynamics
techniques to gather information on the entire lollipop-like Scl2.3 structure.
Molecular dynamics data evidence a high flexibility of Scl2.3 with remarkable
interdomain motions that are likely instrumental to the protein biological
function in mediating adhesive or immune-modulatory functions in host-pathogen
interactions. Altogether, our results provide molecular tools for the
understanding of Scl-mediated streptococcal pathogenesis and important structural
insights for the future design of small molecular inhibitors of streptococcal
invasion.
PMID- 24356967
TI - First step of glycosylphosphatidylinositol (GPI) biosynthesis cross-talks with
ergosterol biosynthesis and Ras signaling in Candida albicans.
AB - Candida albicans is a leading cause of fungal infections worldwide. It has
several glycosylphosphatidylinositol (GPI)-anchored virulence factors. Inhibiting
GPI biosynthesis attenuates its virulence. Building on our previous work, we
explore the interaction of GPI biosynthesis in C. albicans with ergosterol
biosynthesis and hyphal morphogenesis. This study is also the first report of
transcriptional co-regulation existing between two subunits of the multisubunit
enzyme complex, GPI-N-acetylglucosaminyltransferase (GPI-GnT), involved in the
first step of GPI anchor biosynthesis in eukaryotes. Using mutational analysis,
we show that the accessory subunits, GPI2 and GPI19, of GPI-GnT exhibit opposite
effects on ergosterol biosynthesis and Ras signaling (which determines hyphal
morphogenesis). This is because the two subunits negatively regulate one another;
GPI19 mutants show up-regulation of GPI2, whereas GPI2 mutants show up-regulation
of GPI19. Two different models were examined as follows. First, the two GPI-GnT
subunits independently interact with ergosterol biosynthesis and Ras signaling.
Second, the two subunits mutually regulate one another and thereby regulate
sterol levels and Ras signaling. Analysis of double mutants of these subunits
indicates that GPI19 controls ergosterol biosynthesis through ERG11 levels,
whereas GPI2 determines the filamentation by cross-talk with Ras1 signaling.
Taken together, this suggests that the first step of GPI biosynthesis talks to
and regulates two very important pathways in C. albicans. This could have
implications for designing new antifungal strategies.
PMID- 24356968
TI - Dysregulated D-dopachrome tautomerase, a hypoxia-inducible factor-dependent gene,
cooperates with macrophage migration inhibitory factor in renal tumorigenesis.
AB - Clear cell renal cell carcinomas (ccRCCs) are characterized by biallelic loss of
the von Hippel-Lindau tumor suppressor and subsequent constitutive activation of
the hypoxia-inducible factors, whose transcriptional programs dictate major
phenotypic attributes of kidney tumors. We recently described a role for the
macrophage migration inhibitory factor (MIF) in ccRCC as an autocrine-signaling
molecule with elevated expression in tumor tissues and in the circulation of
patients that has potent tumor cell survival effects. MIF is a pleiotropic
cytokine implicated in a variety of diseases and cancers and is the target of
both small molecule and antibody-based therapies currently in clinical trials.
Recent work by others has described D-dopachrome tautomerase (DDT) as a
functional homologue of MIF with a similar genomic structure and expression
patterns. Thus, we sought to determine a role for DDT in renal cancer. We find
that DDT expression mirrors MIF expression in ccRCC tumor sections with high
correlation and that, mechanistically, DDT is a novel hypoxia-inducible gene and
direct target of HIF1alpha and HIF2alpha. Functionally, DDT and MIF demonstrate a
significant overlap in controlling cell survival, tumor formation, and tumor and
endothelial cell migration. However, DDT inhibition consistently displayed more
severe effects on most phenotypes. Accordingly, although dual inhibition of DDT
and MIF demonstrated additive effects in vitro, DDT plays a dominant role in
tumor growth in vivo. Together, our findings identify DDT as a functionally
redundant but more potent cytokine to MIF in cancer and suggest that current
attempts to inhibit MIF signaling may fail because of DDT compensation.
PMID- 24356969
TI - Rbm24, an RNA-binding protein and a target of p53, regulates p21 expression via
mRNA stability.
AB - p21, a cyclin-dependent kinase inhibitor, is necessary for proper control of the
cell cycle and premature senescence. Thus, p21 expression needs to be tightly
controlled. In this study, we found that Rbm24, an RNA-binding protein and a
target gene of the p53 protein, can regulate p21 expression via mRNA stability.
Specifically, we showed that Rbm24 is induced by DNA damage and Mdm2 inhibitor
Nutlin-3. We also found that p53 protein binds to and activates the promoter of
the Rbm24 gene. Moreover, we found that overexpression of Rbm24 increases,
whereas knockdown of Rbm24 decreases, p21 mRNA and protein expression. In
addition, we demonstrated that overexpression of Rbm24 enhances the half-life of
p21 transcript. Consistent with this, we provided evidence that Rbm24 binds to
the 3'-untranslated region (3'-UTR) of p21 transcript and an AU/U-rich element in
the p21 3'-UTR is necessary for Rbm24 to increase p21 expression. Finally, we
showed that the RNA recognition motif in Rbm24 is required for binding to p21
transcript and subsequently for inducing p21 expression. Altogether, we uncovered
that Rbm24 is a novel player in the p53 pathway, which may be explored to restore
proper cell cycle control in p53-deficient tumors via p21.
PMID- 24356970
TI - Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors
targeting the ATP-binding pocket.
AB - Pyruvate dehydrogenase kinase isoforms (PDKs 1-4) negatively regulate activity of
the mitochondrial pyruvate dehydrogenase complex by reversible phosphorylation.
PDK isoforms are up-regulated in obesity, diabetes, heart failure, and cancer and
are potential therapeutic targets for these important human diseases. Here, we
employed a structure-guided design to convert a known Hsp90 inhibitor to a series
of highly specific PDK inhibitors, based on structural conservation in the ATP
binding pocket. The key step involved the substitution of a carbonyl group in the
parent compound with a sulfonyl in the PDK inhibitors. The final compound of this
series, 2-[(2,4-dihydroxyphenyl)sulfonyl]isoindoline-4,6-diol, designated PS10,
inhibits all four PDK isoforms with IC50 = 0.8 MUM for PDK2. The administration
of PS10 (70 mg/kg) to diet-induced obese mice significantly augments pyruvate
dehydrogenase complex activity with reduced phosphorylation in different tissues.
Prolonged PS10 treatments result in improved glucose tolerance and notably
lessened hepatic steatosis in the mouse model. The results support the
pharmacological approach of targeting PDK to control both glucose and fat levels
in obesity and type 2 diabetes.
PMID- 24356972
TI - Concise review: The plasticity of stem cell niches: a general property behind
tissue homeostasis and repair.
AB - Stem cell activity is tightly regulated during development and in adult tissues
through the combined action of local and systemic effectors. While stem cells and
their microenvironments are capable of sustaining homeostasis in normal
physiological circumstances, they also provide host tissues with a remarkable
plasticity to respond to perturbations. Here, we review recent discoveries that
shed light on the adaptive response of niches to systemic signals and aging, and
on the ability of niches to modulate signaling upon local perturbations. These
characteristics of stem cells and their niches give organs an essential advantage
to deal with aging, injury or pathological conditions.
PMID- 24356971
TI - Role of guanine nucleotide exchange factor-H1 in complement-mediated RhoA
activation in glomerular epithelial cells.
AB - Visceral glomerular epithelial cells (GEC), also known as podocytes, are vital
for the structural and functional integrity of the glomerulus. The actin
cytoskeleton plays a central role in maintaining GEC morphology. In a rat model
of experimental membranous nephropathy (passive Heymann nephritis (PHN)),
complement C5b-9-induced proteinuria was associated with the activation of the
actin regulator small GTPase, RhoA. The mechanisms of RhoA activation, however,
remained unknown. In this study, we explored the role of the epithelial guanine
nucleotide exchange factor, GEF-H1, in complement-induced RhoA activation. Using
affinity precipitation to monitor GEF activity, we found that GEF-H1 was
activated in glomeruli isolated from rats with PHN. Complement C5b-9 also induced
parallel activation of GEF-H1 and RhoA in cultured GEC. In GEC in which GEF-H1
was knocked down, both basal and complement-induced RhoA activity was reduced. On
the other hand, GEF-H1 knockdown augmented complement-mediated cytolysis,
suggesting a role for GEF-H1 and RhoA in protecting GEC from cell death. The
MEK1/2 inhibitor, U0126, and mutation of the ERK-dependent phosphorylation site
(T678A) prevented complement-induced GEF-H1 activation, indicating a role for the
ERK pathway. Further, complement induced GEF-H1 and microtubule accumulation in
the perinuclear region. However, both the perinuclear accumulation and the
activation of GEF-H1 were independent of microtubules and myosin-mediated
contractility, as shown using drugs that interfere with microtubule dynamics and
myosin II activity. In summary, we have identified complement-induced ERK
dependent GEF-H1 activation as the upstream mechanism of RhoA stimulation, and
this pathway has a protective role against cell death.
PMID- 24356973
TI - Facile synthesis of beta-diketone alcohols for combined functionality:
initiation, catalysis, and luminescence.
AB - Primary alcohol-functionalized beta-diketones (bdks) are successfully synthesized
via facile one-step Claisen condensation between aromatic monoketones and epsilon
caprolactone (epsilon-CL). To demonstrate application potentials, these bdk
alcohols are used to chelate with various Lewis acids, including Tb (III), Eu
(III), and B (III). It is discovered that the resulting Tb (III) and Eu (III)
diketonate complexes can serve as both catalysts and initiators for ring-opening
polymerization (ROP) under solvent-free conditions, using lactide monomer as an
example. The polylactides (PLAs) thus obtained exhibit luminescence properties
characteristic of Tb (III) and Eu (III), respectively. On the other hand, boron
chelated diketone can initiate ROP of lactide in the presence of Sn(oct)2 , and
affords a PLA material with dual-emission, i.e., fluorescence and room
temperature phosphorescence. The synthesis described here represents a shortcut
for the preparation of bdk-based macroligands and subsequent functional
materials.
PMID- 24356974
TI - Performance of a novel sieving matrix of poly(vinyl alcohol)/acrylamide copolymer
in electrophoretic separations of high molecular weight proteins from red cell
membrane.
AB - The analysis of high molecular weight (HMW) proteins from complex mixtures is
still a challenge in proteomics. This work introduces a novel hydrogel obtained
by the copolymerization of an allyl-PVA derivative with acrylamide and
bisacrylamide and applies this matrix to the electrophoretic separation of HMW
proteins. By inducing gelation of polyacrylamide in the presence of variable
amounts of allyl-PVA, it is possible to control and vary the average gel
porosity. This gel is easy to produce and handle and offers the advantage of
being highly mechanically resistant and macroporous. The new matrix was tested in
mono-dimensional separations of complex protein mixtures extracted from red cell
membranes with different detergents. The improved performance of this macroporous
matrix allowed to identify new proteins by MS and immunoblot analysis using
specific antibodies. In particular, the resolution of proteins ranging in size
between 97 and 279 kDa was greatly improved here compared to standard
polyacrylamide gels, suggesting that this matrix can be a useful tool in routine
analysis of HMW proteins in cell biology.
PMID- 24356976
TI - Family cohesion moderates the relationship between acculturative stress and
depression in Japanese adolescent temporary residents.
AB - Acculturative stress is a risk factor for depression, and may be important in the
risk for depression among acculturating Japanese adolescents. However, little to
no research has been published on the mental health of acculturating Japanese
adolescents. Further, although family cohesion has been shown to be protective
against depression across ethnic groups, no prior research has examined family
cohesion as a protective factor for Japanese adolescents. To examine these
relationships, 26 Japanese temporary resident adolescents and 76 parents in the
Midwest were recruited to participate. Moderate to strong correlations between
acculturative stress, depression, likelihood for and seriousness of family
conflict were found. A regression analysis found that likelihood for family
conflict moderated the relationship between acculturative stress and depression.
Findings broaden our understanding of the role of acculturative stress and family
conflict on depression risk for Japanese adolescent immigrants.
PMID- 24356977
TI - Solution structure of a G-quadruplex bound to the bisquinolinium compound Phen
DC(3).
AB - Phen-DC3 is a highly promising compound that specifically targets G-quadruplexes,
with potent biological effects observed in vivo. We used NMR spectroscopy to
solve the structure of the complex formed between Phen-DC3 and an intramolecular
G-quadruplex derived from the c-myc promoter. Structural information revealed
that Phen-DC3 interacts with the quadruplex through extensive pi-stacking with
guanine bases of the top G-tetrad. On the basis of our structure, modifications
are proposed for the development of this compound for selective targeting of a
specific G-quadruplex conformation.
PMID- 24356978
TI - Structural characterization of a ligand-bound form of Bacillus subtilis FadR
involved in the regulation of fatty acid degradation.
AB - Bacillus subtilis FadR (FadR(Bs)), a member of the TetR family of bacterial
transcriptional regulators, represses five fad operons including 15 genes, most
of which are involved in beta-oxidation of fatty acids. FadR(Bs) binds to the
five FadR(Bs) boxes in the promoter regions and the binding is specifically
inhibited by long-chain (C14-C20 ) acyl-CoAs, causing derepression of the fad
operons. To elucidate the structural mechanism of this regulator, we have
determined the crystal structures of FadR(Bs) proteins prepared with and without
stearoyl(C18)-CoA. The crystal structure without adding any ligand molecules
unexpectedly includes one small molecule, probably dodecyl(C12)-CoA derived from
the Escherichia coli host, in its homodimeric structure. Also, we successfully
obtained the structure of the ligand-bound form of the FadR(Bs) dimer by co
crystallization, in which two stearoyl-CoA molecules are accommodated, with the
binding mode being essentially equivalent to that of dodecyl-CoA. Although the
acyl-chain-binding cavity of FadR(Bs) is mainly hydrophobic, a hydrophilic patch
encompasses the C1-C10 carbons of the acyl chain. This accounts for the previous
report that the DNA binding of FadR(Bs) is specifically inhibited by the long
chain acyl-CoAs but not by the shorter ones. Structural comparison of the ligand
bound and unliganded subunits of FadR(Bs) revealed three regions around residues
21-31, 61-76, and 106-119 that were substantially changed in response to the
ligand binding, and particularly with respect to the movements of Leu108 and
Arg109. Site-directed mutagenesis of these residues revealed that Arg109, but not
Leu108, is a key residue for maintenance of the DNA-binding affinity of FadR(Bs).
PMID- 24356979
TI - Cystic diseases of the liver and bile ducts.
PMID- 24356981
TI - Community structure and PAH ring-hydroxylating dioxygenase genes of a marine
pyrene-degrading microbial consortium.
AB - Marine microbial consortium UBF, enriched from a beach polluted by the Prestige
oil spill and highly efficient in degrading this heavy fuel, was subcultured in
pyrene minimal medium. The pyrene-degrading subpopulation (UBF-Py) mineralized 31
% of pyrene without accumulation of partially oxidized intermediates indicating
the cooperation of different microbial components in substrate mineralization.
The microbial community composition was characterized by culture dependent and
PCR based methods (PCR-DGGE and clone libraries). Molecular analyses showed a
highly stable community composed by Alphaproteobacteria (84 %, Breoghania,
Thalassospira, Paracoccus, and Martelella) and Actinobacteria (16 %, Gordonia).
The members of Thalasosspira and Gordonia were not recovered as pure cultures,
but five additional strains, not detected in the molecular analysis, that
classified within the genera Novosphingobium, Sphingopyxis, Aurantimonas
(Alphaproteobacteria), Alcanivorax (Gammaproteobacteria) and Micrococcus
(Actinobacteria), were isolated. None of the isolates degraded pyrene or other
PAHs in pure culture. PCR amplification of Gram-positive and Gram-negative
dioxygenase genes did not produce results with any of the cultured strains.
However, sequences related to the NidA3 pyrene dioxygenase present in
mycobacterial strains were detected in UBF-Py consortium, suggesting the
representative of Gordonia as the key pyrene degrader, which is consistent with a
preeminent role of actinobacteria in pyrene removal in coastal environments
affected by marine oil spills.
PMID- 24356980
TI - Prevalence of systemic inflammation and micronutrient imbalance in patients with
complex abdominal hernias.
AB - OBJECTIVE: To determine the prevalence of low-grade inflammation, micronutrient
imbalances and associated clinical profiles in patients being evaluated for
complex abdominal hernia repair. METHODS: Review of 127 consecutive adult
patients for evaluation of complex ventral hernias from January 2012 to March
2013. Records were analyzed to determine the prevalence and correlations of
clinical risk factors, attributes of hernias identified by computerized
tomography, and laboratory indices of metabolism, inflammation and micronutrient
imbalances. RESULTS: Strong correlations (p < 0.001) were established for body
mass index (BMI) with volume of hernia content and C-reactive protein (CRP)
level. CRP levels correlated strongly with red cell distribution width and
inversely with zinc (p < 0.01). Evidence of micronutrient imbalance (abnormal
zinc or red cell distribution width [RDW]) was observed in 48%. CONCLUSIONS: In
this comorbidity-rich population with known variability in surgical outcomes, the
prevalence of chronic inflammation and micronutrient deficiency are high enough
to warrant systemic preoperative evaluation given their possible effect on wound
healing and convalescence. Simple repletion is unlikely to improve outcomes
without attention to the biological stresses that are associated with
micronutrient imbalance.
PMID- 24356983
TI - Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro
inflammation.
AB - Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked
by the invasion of the central nervous system by monocyte-derived macrophages and
autoreactive T cells across the brain vasculature. Data from experimental animal
models recently implied that the passage of leukocytes across the brain
vasculature is preceded by their traversal across the blood-cerebrospinal fluid
barrier (BCSFB) of the choroid plexus. The correlation between the presence of
leukocytes in the CSF of patients suffering from MS and the number of
inflammatory lesions as detected by magnetic resonance imaging suggests that
inflammation at the choroid plexus contributes to the disease, although in a yet
unknown fashion. We here provide first insights into the involvement of the
choroid plexus in the onset and severity of the disease and in particular address
the role of the tight junction protein claudin-3 (CLDN3) in this process.
Detailed analysis of human post-mortem brain tissue revealed a selective loss of
CLDN3 at the choroid plexus in MS patients compared to control tissues.
Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more
rapid onset and exacerbated clinical signs of experimental autoimmune
encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes
in their CSF. Together, this study highlights a profound role for the choroid
plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be
regarded as a crucial and novel determinant of BCSFB integrity.
PMID- 24356984
TI - The neuropathology associated with repeat expansions in the C9ORF72 gene.
AB - An abnormal expansion of a GGGGCC hexanucleotide repeat in a non-coding region of
the chromosome 9 open reading frame 72 gene (C9ORF72) is the most common genetic
abnormality in familial and sporadic FTLD and ALS and the cause in most families
where both, FTLD and ALS, are inherited. Pathologically, C9ORF72 expansion cases
show a combination of FTLD-TDP and classical ALS with abnormal accumulation of
TDP-43 into neuronal and oligodendroglial inclusions consistently seen in the
frontal and temporal cortex, hippocampus and pyramidal motor system. In addition,
a highly specific feature in C9ORF72 expansion cases is the presence of ubiquitin
and p62 positive, but TDP-43 negative neuronal cytoplasmic and intranuclear
inclusions. These TDP-43 negative inclusions contain dipeptide-repeat (DPR)
proteins generated by unconventional repeat-associated translation of C9ORF72
transcripts with the expanded repeats and are most abundant in the cerebellum,
hippocampus and all neocortex regions. Another consistent pathological feature
associated with the production of C9ORF72 transcripts with expanded repeats is
the formation of nuclear RNA foci that are frequently observed in the frontal
cortex, hippocampus and cerebellum. Here, we summarize the complexity and
heterogeneity of the neuropathology associated with the C9ORF72 expansion. We
discuss implications of the data to the current classification of FTLD and
critically review current insights from clinico-pathological correlative studies
regarding the fundamental questions as to what processes are required and
sufficient to trigger neurodegeneration in C9ORF72 disease pathogenesis.
PMID- 24356982
TI - Cognitive and social lifestyle: links with neuropathology and cognition in late
life.
AB - Many studies report an association of cognitive and social experiential factors
and related traits with dementia risk. Further, many clinical-pathologic studies
find a poor correspondence between levels of neuropathology and the presence of
dementia and level of cognitive impairment. The poor correspondence suggests that
other factors contribute to the maintenance or loss of cognitive function, with
factors associated with the maintenance of function referred to as neural or
cognitive reserve. This has led investigators to examine the associations of
cognitive and social experiential factors with neuropathology as a first step in
disentangling the complex associations between these experiential risk factors,
neuropathology, and cognitive impairment. Despite the consistent associations of
a range of cognitive and social lifestyle factors with cognitive decline and
dementia risk, the extant clinical-pathologic data find only a single factor from
one cohort, linguistic ability, related to AD pathology. Other factors, including
education, harm avoidance, and emotional neglect, are associated with
cerebrovascular disease. Overall, the associations are weak. Some factors, such
as education, social networks, and purpose in life, modify the relation of
neuropathology to cognition. Finally, some factors such as cognitive activity
appear to bypass known pathologies altogether suggesting a more direct
association with biologic indices that promote person-specific differences in
reserve and resilience. Future work will first need to replicate findings across
more studies to ensure the veracity of the existing data. Second, effort is
needed to identify the molecular substrates of neural reserve as potential
mediators of the association of lifestyle factors with cognition.
PMID- 24356985
TI - Development of the mechanical properties of engineered skin substitutes after
grafting to full-thickness wounds.
AB - Engineered skin substitutes (ESSs) have been reported to close full-thickness
burn wounds but are subject to loss from mechanical shear due to their
deficiencies in tensile strength and elasticity. Hypothetically, if the
mechanical properties of ESS matched those of native skin, losses due to shear or
fracture could be reduced. To consider modifications of the composition of ESS to
improve homology with native skin, biomechanical analyses of the current
composition of ESS were performed. ESSs consist of a degradable biopolymer
scaffold of type I collagen and chondroitin-sulfate (CGS) that is populated
sequentially with cultured human dermal fibroblasts (hF) and epidermal
keratinocytes (hK). In the current study, the hydrated biopolymer scaffold (CGS),
the scaffold populated with hF dermal skin substitute (DSS), or the complete ESS
were evaluated mechanically for linear stiffness (N/mm), ultimate tensile load at
failure (N), maximum extension at failure (mm), and energy absorbed up to the
point of failure (N-mm). These biomechanical end points were also used to
evaluate ESS at six weeks after grafting to full-thickness skin wounds in athymic
mice and compared to murine autograft or excised murine skin. The data showed
statistically significant differences (p <0.05) between ESS in vitro and after
grafting for all four structural properties. Grafted ESS differed statistically
from murine autograft with respect to maximum extension at failure, and from
intact murine skin with respect to linear stiffness and maximum extension. These
results demonstrate rapid changes in mechanical properties of ESS after grafting
that are comparable to murine autograft. These values provide instruction for
improvement of the biomechanical properties of ESS in vitro that may reduce
clinical morbidity from graft loss.
PMID- 24356986
TI - Sub-classification of Stage II colorectal cancer based on clinicopathological
risk factors for recurrence.
AB - PURPOSE: To make a Stage II colorectal cancer (CRC) sub-classification based on
clinicopathological factors. METHODS: The subjects of this study were 422
patients with Stage II CRC, who underwent curative surgery with dissection of
more than 12 lymph nodes. We used the logistic regression analysis or model and
Cox's proportional hazard regression model for analysis. RESULTS: Preoperative
carcinoembryonic antigen (CEA) level (p = 0.0057), macroscopic type (p = 0.0316),
and depth of invasion (p = 0.0401) were extracted as independent risk factors for
recurrence, whereas the preoperative CEA level (p = 0.0045) and depth of invasion
(p = 0.0395) were extracted as independent predictors of 5-year disease-free
survival. We defined depth of invasion (pT4) and the preoperative CEA level
(abnormal) as risk factors for recurrence, and classified Grade A as a normal CEA
level regardless of depth invasion, Grade B as depth of invasion to pT3 and an
elevated CEA level, and Grade C as depth of invasion to pT4 and an elevated CEA
level. There were significant differences in cumulative 5-year disease-free
survival rates among each grade (Grade A vs. Grade B, p = 0.0474; Grade A vs.
Grade C, p < 0.0001; Grade B vs. Grade C, p = 0.0134). CONCLUSION: The sub
classification of Stage II CRC, according not only to depth of invasion but also
to preoperative CEA level, is important for predicting the prognosis.
PMID- 24356987
TI - Peptide conjugates for directing the morphology and assembly of 1D nanoparticle
superstructures.
AB - Designed peptide conjugates molecules are used to direct the synthesis and
assembly of gold nanoparticles into complex 1D nanoparticle superstructures with
various morphologies. Four peptide conjugates, each based on the gold-binding
peptide (AYSSGAPPMPPF; PEPAu ), are prepared: C12H23O-AYSSGAPPMPP (1), C12H23O
AYSSGAPPMPPF (2), C12H23O-AYSSGAPPMPPFF (3), and C12H23O-AYSSGAPPMPPFFF (4). The
affect that C-terminal hydrophobic F residues have on both the soft-assembly of
the peptide conjugates and the resulting assembly of gold nanoparticle
superstructures is examined. It is shown that the addition of two C-terminal F
residues (3) leads to thick, branched 1D gold nanoparticle superstructures,
whereas the addition of three C-terminal F residues (4) leads to bundling of thin
1D nanoparticle superstructures.
PMID- 24356989
TI - Growth behavior and electrical performance of Ga-doped ZnO nanorod/p-Si
heterojunction diodes prepared using a hydrothermal method.
AB - The incorporation of foreign elements into ZnO nanostructures is of significant
interest for tuning the structure and optical and electrical properties in
nanoscale optoelectronic devices. In this study, Ga-doped 1-D ZnO nanorods were
synthesized using a hydrothermal route, in which the doping content of Ga was
varied from 0% to 10%. The pn heterojunction diodes based on the n-type Ga-doped
ZnO nanorod/p-type Si substrates were constructed, and the effect of the Ga
doping on the morphology, chemical bonding structure, and optical properties of
the ZnO nanorods was systematically investigated as well as the diode
performance. With increasing Ga content, the average diameter of the ZnO nanorods
was increased, whereas the amount of oxygen vacancies was reduced. In addition,
the Ga-doped ZnO nanorod/p-Si diodes showed a well-defined rectifying behavior in
the I-V characteristics and an improvement in the electrical conductivity (diode
performance) by the Ga doping, which was attributed to the increased charge
carrier (electron) concentration and the reduced defect states in the nanorods by
incorporating Ga. The results suggest that Ga doping is an effective way to
tailor the morphology, optical, electronic, and electrical properties of ZnO
nanorods for various applications such as field-effect transistors (FETs), light
emitting diodes (LEDs), and laser diodes (LDs).
PMID- 24356988
TI - A novel method for detecting uniparental disomy from trio genotypes identifies a
significant excess in children with developmental disorders.
AB - Exome sequencing of parent-offspring trios is a popular strategy for identifying
causative genetic variants in children with rare diseases. This method owes its
strength to the leveraging of inheritance information, which facilitates de novo
variant calling, inference of compound heterozygosity, and the identification of
inheritance anomalies. Uniparental disomy describes the inheritance of a
homologous chromosome pair from only one parent. This aberration is important to
detect in genetic disease studies because it can result in imprinting disorders
and recessive diseases. We have developed a software tool to detect uniparental
disomy from child-mother-father genotype data that uses a binomial test to
identify chromosomes with a significant burden of uniparentally inherited
genotypes. This tool is the first to read VCF-formatted genotypes, to perform
integrated copy number filtering, and to use a statistical test inherently robust
for use in platforms of varying genotyping density and noise characteristics.
Simulations demonstrated superior accuracy compared with previously developed
approaches. We implemented the method on 1057 trios from the Deciphering
Developmental Disorders project, a trio-based rare disease study, and detected
six validated events, a significant enrichment compared with the population
prevalence of UPD (1 in 3500), suggesting that most of these events are
pathogenic. One of these events represents a known imprinting disorder, and exome
analyses have identified rare homozygous candidate variants, mainly in the
isodisomic regions of UPD chromosomes, which, among other variants, provide
targets for further genetic and functional evaluation.
PMID- 24356990
TI - Efficient computation of root mean square deviations under rigid transformations.
AB - The computation of root mean square deviations (RMSD) is an important step in
many bioinformatics applications. If approached naively, each RMSD computation
takes time linear in the number of atoms. In addition, a careful implementation
is required to achieve numerical stability, which further increases runtimes. In
practice, the structural variations under consideration are often induced by
rigid transformations of the protein, or are at least dominated by a rigid
component. In this work, we show how RMSD values resulting from rigid
transformations can be computed in constant time from the protein's covariance
matrix, which can be precomputed in linear time. As a typical application
scenario is protein clustering, we will also show how the Ward-distance which is
popular in this field can be reduced to RMSD evaluations, yielding a constant
time approach for their computation.
PMID- 24356991
TI - Alternatives to switch-cost scoring in the task-switching paradigm: their
reliability and increased validity.
AB - In the task-switching paradigm, the latency switch-cost score-the difference in
mean reaction time between switch and nonswitch trials-is the traditional measure
of task-switching ability. However, this score does not reflect accuracy, where
switch costs may also emerge. In two experiments that varied in response
deadlines (unlimited vs. limited time), we evaluated the measurement properties
of two traditional switch-cost scoring methods (the latency switch-cost score and
the accuracy switch-cost score) and three alternatives (a rate residual score, a
bin score, and an inverse efficiency score). Scores from the rate residual, bin
score, and inverse efficiency methods had comparable reliability for latency
switch-cost scores without response deadlines but were more reliable than latency
switch-cost scores when higher error rates were induced with a response deadline.
All three alternative scoring methods appropriately accounted for differences in
accuracy switch costs when higher error rates were induced, whereas pure latency
switch-cost scores did not. Critically, only the rate residual and bin score
methods were more valid indicators of task-switching ability; they demonstrated
stronger relationships with performance on an independent measure of executive
functioning (the antisaccade analogue task), and they allowed the detection of
larger effect sizes when examining within-task congruency effects. All of the
three alternative scoring methods provide researchers with a better measure of
task-switching ability than do traditional scoring methods, because they each
simultaneously account for latency and accuracy costs. Overall, the three
alternative scoring methods were all superior to the traditional latency switch
cost scoring method, but the strongest methods were the rate residual and bin
score methods.
PMID- 24356992
TI - The Centre for Speech, Language and the Brain (CSLB) concept property norms.
AB - Theories of the representation and processing of concepts have been greatly
enhanced by models based on information available in semantic property norms.
This information relates both to the identity of the features produced in the
norms and to their statistical properties. In this article, we introduce a new
and large set of property norms that are designed to be a more flexible tool to
meet the demands of many different disciplines interested in conceptual knowledge
representation, from cognitive psychology to computational linguistics. As well
as providing all features listed by 2 or more participants, we also show the
considerable linguistic variation that underlies each normalized feature label
and the number of participants who generated each variant. Our norms are highly
comparable with the largest extant set (McRae, Cree, Seidenberg, & McNorgan,
2005) in terms of the number and distribution of features. In addition, we show
how the norms give rise to a coherent category structure. We provide these norms
in the hope that the greater detail available in the Centre for Speech, Language
and the Brain norms should further promote the development of models of
conceptual knowledge. The norms can be downloaded at
www.csl.psychol.cam.ac.uk/propertynorms.
PMID- 24356993
TI - A low-cost visual occlusion device.
AB - In this article, we propose a method to develop a low-cost visual occlusion
device. This device is modified using three-dimensional (3-D) glasses (used to
watch 3-D TV) that are operated via the active shutter technique. Because 3-D
glasses are sold worldwide, they are readily available; moreover, the price of 3
D glasses is lower than that of other types of equipment used as the basis for
visual occlusion devices. Three-dimensional glasses employing the active shutter
technique have the same structure as do commercial visual occlusion devices; the
modification of a voltage-driven liquid crystal display is fairly simple. In this
study, we evaluated the response time and transparency of the proposed low-cost
visual occlusion device; the experiments yielded reasonable results. The proposed
visual occlusion device can be fabricated under a price of $100.
PMID- 24356994
TI - An integrated ball projection technology for the study of dynamic interceptive
actions.
AB - Dynamic interceptive actions, such as catching or hitting a ball, are important
task vehicles for investigating the complex relationship between cognition,
perception, and action in performance environments. Representative experimental
designs have become more important recently, highlighting the need for research
methods to ensure that the coupling of information and movement is faithfully
maintained. However, retaining representative design while ensuring systematic
control of experimental variables is challenging, due to the traditional tendency
to employ methods that typically involve use of reductionist motor responses such
as buttonpressing or micromovements. Here, we outline the methodology behind a
custom-built, integrated ball projection technology that allows images of
advanced visual information to be synchronized with ball projection. This
integrated technology supports the controlled presentation of visual information
to participants while they perform dynamic interceptive actions. We discuss
theoretical ideas behind the integration of hardware and software, along with
practical issues resolved in technological design, and emphasize how the system
can be integrated with emerging developments such as mixed reality environments.
We conclude by considering future developments and applications of the integrated
projection technology for research in human movement behaviors.
PMID- 24356995
TI - A comparison of sequential and nonsequential specification searches in testing
factorial invariance.
AB - The purpose of this study was to examine the performance of modification indices
(MIs) in finding correct partial invariance models when testing factorial
invariance across groups of interest. In the present study, we examined the two
commonly used approaches in this area-namely, nonsequential search and sequential
search. Using the nonsequential search procedure, partial invariance models can
be found by relaxing at once all the MIs larger than a certain cutoff value
(usually, 3.84) at the first place, whereas in the sequential search method, the
models are modified by relaxing one constrained parameter (usually the parameter
with the largest MI) at a time and reanalyzing the models after each parameter
has been relaxed. Our simulation results showed that the nonsequential search can
lead to extremely high false positive rates and that it is highly likely that
some invariant items will be incorrectly identified as noninvariant. In
consequence, the nonsequential search method will likely lead to inadequately
modifying scales. However, the sequential search method using MIs performed well
and produced good true positive and false positive rates across all simulation
conditions. Recommendations based on the findings are provided, and limitations
of the study are discussed.
PMID- 24356996
TI - Reputation as a sufficient condition for data quality on Amazon Mechanical Turk.
AB - Data quality is one of the major concerns of using crowdsourcing websites such as
Amazon Mechanical Turk (MTurk) to recruit participants for online behavioral
studies. We compared two methods for ensuring data quality on MTurk: attention
check questions (ACQs) and restricting participation to MTurk workers with high
reputation (above 95% approval ratings). In Experiment 1, we found that high
reputation workers rarely failed ACQs and provided higher-quality data than did
low-reputation workers; ACQs improved data quality only for low-reputation
workers, and only in some cases. Experiment 2 corroborated these findings and
also showed that more productive high-reputation workers produce the highest
quality data. We concluded that sampling high-reputation workers can ensure high
quality data without having to resort to using ACQs, which may lead to selection
bias if participants who fail ACQs are excluded post-hoc.
PMID- 24356997
TI - UVB-induced anti-survival and pro-apoptotic effects on HaCaT human keratinocytes
via caspase- and PKC-dependent downregulation of PKB, HIAP-1, Mcl-1, XIAP and ER
stress.
AB - Evidence suggests that solar ultraviolet B (UVB) radiation inhibits growth and/or
induces apoptosis of human skin cells. However, mechanisms underlying the UVB
induced anti-survival and pro-apoptotic effects on human skin cells remain
unclear. In this study, we investigated the effect of UVB radiation on survival
and apoptosis of HaCaT human keratinocytes and determined possible molecular,
cellular and signaling mechanisms including cross-regulation, which are
responsible for the UVB's anti-survival and/or pro-apoptotic effects. The results
showed that UVB radiation at 400 mJ/cm2 for 8 h largely decreased cell survival
and induced DNA fragmentation, an index of apoptosis, in HaCaT human
keratinocytes. On a mechanistic level, UVB radiation triggered the activation of
caspase-9, cleavage of poly(ADP-ribose) polymerase, and downregulation of myeloid
cell leukemia-1 (Mcl-1), human inhibitor of apoptosis protein-1 (HIAP-1), X
linked IAP (XIAP), and protein kinase B (PKB), but did not affect the expression
of B-cell lymphoma-2 in HaCaT cells. UVB radiation also upregulated the
expression of glucose-regulated protein 78 (GRP78), an endoplasmic reticulum (ER)
stress marker, in HaCaT cells. Of note, results of pharmacological inhibition
studies have demonstrated that pretreatment with z-VAD-fmk, a pan-caspase
inhibitor strongly attenuated UVB-induced apoptosis, the activation of caspase-9,
downregulation of Mcl-1, XIAP and PKB (but not HIAP-1), and upregulation of
GRP78, while pretreatment with GF109203 or GO6983, pan-PKC inhibitors,
substantially blocked the UVB-induced reduction of cell survival, activation of
caspase-9, downregulation of HIAP-1, XIAP, and PKB (but not Mcl-1), and GRP78
upregulation in HaCaT cells. Collectively, these results demonstrated that UVB
has strong anti-survival and pro-apoptotic effects on HaCaT cells and the effects
were largely mediated via the activation of caspase-9 and protein kinase Cs,
which subsequently downregulated PKB, XIAP, HIAP-1 and Mcl-1, and triggered ER
stress.
PMID- 24356998
TI - HtrA1 downregulation induces cisplatin resistance in lung adenocarcinoma by
promoting cancer stem cell-like properties.
AB - Cisplatin (CDDP) resistance usually develops during lung adenocarcinoma (LAC)
therapy. However, the comprehensive mechanisms remain largely unclear. In this
study, we first established a CDDP-resistant LAC cell line-A549/CDDP from its
parental cell line-A549. The results showed that CDDP resistance in A549/CDDP
cells correlates with acquirement of cancer stem cell-like properties (increased
percentage of CD133-expressing subpopulation, sphere formation and levels of some
pluripotency-associated markers). HtrA1 expression at both mRNA and protein
levels was reduced in CDDP-resistant A549/CDDP cells compared with that in A549
cells. Ectopic expression of HtrA1 in A549/CDDP cells reversed cancer stem cell
like properties and CDDP resistance. In A549 cells, stable knockdown of HtrA1
expression promoted cancer stem cell-like properties and CDDP insensitivity,
however, these effects were blocked by inhibition of PI3K/Akt pathway using
LY294002. Furthermore, HtrA1 knockdown could significantly stimulate PI3K/Akt
signaling in A549 cells. In vivo studies, HtrA1 knockdown promoted tumorigenesis
and conferred CDDP resistance in xenograft A549 tumors, which were reversed by
intraperitoneal injection of LY294002. In conclusion, these results indicate that
HtrA1 downregulation confers CDDP resistance by inducing cancer stem cell-like
properties via PI3K/Akt-dependent pathway in A549 cells. Therefore, HtrA1 may be
a potential target for overcoming CDDP resistance in LAC.
PMID- 24356999
TI - Munich lung transplant group: waiting list during the first 9 months of the lung
allocation score era.
AB - OBJECTIVE AND METHODS: The Eurotransplant Foundation introduced the lung
allocation score (LAS) in Germany on December 10, 2011. We analyzed
characteristics of the Munich Lung Transplant Group (MLTG) waiting list during
the first 9 months after the introduction of the LAS. RESULTS: A mean number of
39 +/- 1 patients were constantly listed for lung transplantation and 60
transplants were performed by the MLTG during the observation period. While the
majority (42 +/- 0%) of patients waiting for transplant comprised chronic
obstructive pulmonary disease (COPD)/emphysema patients, only 26% of transplanted
patients suffered from COPD/emphysema. Instead, the majority (42%) of
transplanted patients suffered from interstitial lung disease. Waiting times did
not markedly change in the LAS era. Notably, patients with interstitial lung
disease had shorter waiting times when compared with patients suffering from
COPD/emphysema and cystic fibrosis, both on the waiting list and at the time of
transplant. CONCLUSION: The MLTG lung transplant waiting list has not markedly
changed during the first 9 months after the introduction of the LAS. Our data
indicate that the LAS accommodates disease-specific patient statuses well.
Although patients with interstitial lung disease are preferably transplanted, the
LAS system provides a very reasonable basis to also list and transplant
COPD/emphysema patients.
PMID- 24357000
TI - Turning the digital page at ChemBioChem.
AB - Chemical biology has been in the spotlight for numerous reasons lately.
ChemBioChem has had a productive year at the forefront of these advances and is
looking forward to many changes in 2014. Advances in digital publishing promise
to increase the visibility and functionality of ChemBioChem for our worldwide
readership.
PMID- 24357003
TI - E1-catalyzed ubiquitin C-terminal amidation for the facile synthesis of
deubiquitinase substrates.
AB - Will Ub my partner? The ubiquitin (Ub)-activating enzyme (E1) was used to
catalyze an amidation reaction to functionalize the C terminus of Ub with unique
functional groups, such as thiol, azide, alkyne, and alkene groups, with high
efficiency and yield (>90 %). These groups were then applied for the facile
synthesis of fluorophore-conjugated ubiquitin and specifically conjugated
diubiquitin substrates for deubiquitinases.
PMID- 24357004
TI - Chemoenzymatic bio-orthogonal chemistry for site-specific double modification of
recombinant thrombomodulin.
AB - Best of both worlds: A one-pot strategy for site-specific PEGylation through
strain-promoted alkyne-azide cycloaddition (SPAAC) and fluorescent labeling
through sortase A-mediated ligation (SML) of recombinant thrombomodulin without
prior chemical modification and without diminishing the protein activity has been
developed.
PMID- 24357005
TI - Real time hybridization studies by resonant waveguide gratings using nanopattern
imaging for Single Nucleotide Polymorphism detection.
AB - 2D imaging of biochips is particularly interesting for multiplex biosensing.
Resonant properties allow label-free detection using the change of refractive
index at the chip surface. We demonstrate a new principle of Scanning Of
Resonance on Chip by Imaging (SORCI) based on spatial profiles of nanopatterns of
resonant waveguide gratings (RWGs) and its embodiment in a fluidic chip for real
time biological studies. This scheme allows multiplexing of the resonance itself
by providing nanopattern sensing areas in a bioarray format. Through several chip
designs we discuss resonance spatial profiles, dispersion and electric field
distribution for optimal light-matter interaction with biological species of
different sizes. Fluidic integration is carried out with a black anodized
aluminum chamber, advantageous in term of mechanical stability, multiple uses of
the chip, temperature control and low optical background. Real-time hybridization
experiments are illustrated by SNP (Single Nucleotide Polymorphism) detection in
gyrase A of E. coli K12, observed in evolution studies of resistance to the
antibiotic ciprofloxacin. We choose a 100 base pairs (bp) DNA target (~30 kDa)
including the codon of interest and demonstrate the high specificity of our
technique for probes and targets with close affinity constants. This work
validates the safe applicability of our unique combination of RWGs and simple
instrumentation for real-time biosensing with sensitivity in buffer solution of
~10 pg/mm2. Paralleling the success of RWGs sensing for cells sensing, our work
opens new avenues for a large number of biological studies.
PMID- 24357007
TI - Fenretinide induces ubiquitin-dependent proteasomal degradation of stearoyl-CoA
desaturase in human retinal pigment epithelial cells.
AB - Stearoyl-CoA desaturase (SCD, SCD1), an endoplasmic reticulum (ER) resident
protein and a rate-limiting enzyme in monounsaturated fatty acid biosynthesis,
regulates cellular functions by controlling the ratio of saturated to
monounsaturated fatty acids. Increase in SCD expression is strongly implicated in
the proliferation and survival of cancer cells, whereas its decrease is known to
impair proliferation, induce apoptosis, and restore insulin sensitivity. We
examined whether fenretinide, (N-(4-hydroxyphenyl)retinamide, 4HPR), which
induces apoptosis in cancer cells and recently shown to improve insulin
sensitivity, can modulate the expression of SCD. We observed that fenretinide
decreased SCD protein and enzymatic activity in the ARPE-19 human retinal pigment
epithelial cell line. Increased expression of BiP/GRP78, ATF4, and GADD153
implicated ER stress. Tunicamycin and thapsigargin, compounds known to induce ER
stress, also decreased the SCD protein. This decrease was completely blocked by
the proteasome inhibitor MG132. In addition, PYR41, an inhibitor of ubiquitin
activating enzyme E1, blocked the fenretinide-mediated decrease in SCD.
Immunoprecipitation analysis using anti-ubiquitin and anti-SCD antibodies and the
blocking of SCD loss by PYR41 inhibition of ubiquitination further corroborate
that fenretinide mediates the degradation of SCD in human RPE cells via the
ubiquitin-proteasome dependent pathway. Therefore, the effect of fenretinide on
SCD should be considered in its potential therapeutic role against cancer, type-2
diabetes, and retinal diseases.
PMID- 24357009
TI - International interlaboratory study for sizing and quantification of Ag
nanoparticles in food simulants by single-particle ICPMS.
AB - This publication describes the first international intercomparison of particle
size determination by single-particle inductively coupled plasma mass
spectrometry (sp-ICPMS). Concentrated monodisperse silver nanoparticle
suspensions with particle diameters of 20, 40 and 100 nm and a blank solution
were sent to 23 laboratories in Europe, the USA and Canada. Laboratories prepared
eight nanoparticle preparations in two food simulants (distilled water; 10%
ethanol) and reported median particle size, Ag particle mass concentration and Ag
particle number concentrations. Average repeatability and reproducibility
standard deviation (sr and sR) for the median particle diameter were 1 and 14 nm,
respectively. Relative precision was worse for Ag particle number concentrations
(RSD r = 11%; RSD R = 78%). While further improvements of the method, especially
with respect to software tools for evaluation, hardware options for shorter dwell
times, calibration standards for determining nebuliser efficiency and further
experience by laboratories are certainly desirable, the results of this study
demonstrate the suitability of sp-ICPMS for the detection and quantification of
certain kinds of nanoparticles.
PMID- 24357008
TI - Sizing up large protein complexes by electrospray ionisation-based
electrophoretic mobility and native mass spectrometry: morphology selective
binding of Fabs to hepatitis B virus capsids.
AB - The capsid of hepatitis B virus (HBV) is a major viral antigen and important
diagnostic indicator. HBV capsids have prominent protrusions ('spikes') on their
surface and are unique in having either T = 3 or T = 4 icosahedral symmetry.
Mouse monoclonal and also human polyclonal antibodies bind either near the spike
apices (historically the 'alpha-determinant') or in the 'floor' regions between
them (the 'beta-determinant'). Native mass spectrometry (MS) and gas-phase
electrophoretic mobility molecular analysis (GEMMA) were used to monitor the
titration of HBV capsids with the antigen-binding domain (Fab) of mAb 3120, which
has long defined the beta-determinant. Both methods readily distinguished Fab
binding to the two capsid morphologies and could provide accurate masses and
dimensions for these large immune complexes, which range up to ~8 MDa. As such,
native MS and GEMMA provide valuable alternatives to a more time-consuming cryo
electron microscopy analysis for preliminary characterisation of virus-antibody
complexes.
PMID- 24357010
TI - A high-throughput method for GMO multi-detection using a microfluidic dynamic
array.
AB - The ever-increasing production of genetically modified crops generates a demand
for high-throughput DNA-based methods for the enforcement of genetically modified
organisms (GMO) labelling requirements. The application of standard real-time PCR
will become increasingly costly with the growth of the number of GMOs that is
potentially present in an individual sample. The present work presents the
results of an innovative approach in genetically modified crops analysis by DNA
based methods, which is the use of a microfluidic dynamic array as a high
throughput multi-detection system. In order to evaluate the system, six test
samples with an increasing degree of complexity were prepared, preamplified and
subsequently analysed in the Fluidigm system. Twenty-eight assays targeting
different DNA elements, GM events and species-specific reference genes were used
in the experiment. The large majority of the assays tested presented expected
results. The power of low level detection was assessed and elements present at
concentrations as low as 0.06 % were successfully detected. The approach proposed
in this work presents the Fluidigm system as a suitable and promising platform
for GMO multi-detection.
PMID- 24357011
TI - The role of religion and spirituality in coping with type 2 diabetes: a
qualitative study among Black men.
AB - Religion and spirituality are instrumental to coping with health; however, there
is limited literature on the use of religion and spirituality among Black men
with type 2 diabetes. The purpose of this study is to explore how Black men use
religion or spirituality to cope with diabetes management. We conducted in-depth
interviews with 30 Black men recruited from a diabetes clinic in Atlanta, Georgia
as part of a larger study. This article reports on data from 12 of the 30 Black
men who reported the use of religion and spirituality as a coping strategy for
diabetes management. The following coping strategies were reported: prayer and
belief in God, keeping me alive, turning things over to God, changing my
unhealthy behaviors, supplying my needs, reading the Bible, and religious or
spiritual individuals helping me. Healthcare professionals and researchers
involved in diabetes management among Black men should consider these findings in
their efforts.
PMID- 24357012
TI - Capsule commentary on Michaelidis et al., Cost-effectiveness of procalcitonin
guided antibiotic therapy for outpatient management of acute respiratory tract
infections in adults.
PMID- 24357013
TI - Capsule commentary on Gallagher et al., Internists' attitudes about assessing and
maintaining clinical competence.
PMID- 24357014
TI - Defined human pluripotent stem cell culture enables highly efficient
neuroepithelium derivation without small molecule inhibitors.
AB - The embryonic neuroepithelium gives rise to the entire central nervous system in
vivo, making it an important tissue for developmental studies and a prospective
cell source for regenerative applications. Current protocols for deriving
homogenous neuroepithelial cultures from human pluripotent stem cells (hPSCs)
consist of either embryoid body-mediated neuralization followed by a manual
isolation step or adherent differentiation using small molecule inhibitors. Here,
we report that hPSCs maintained under chemically defined, feeder-independent, and
xeno-free conditions can be directly differentiated into pure neuroepithelial
cultures ([mt]90% Pax6(+)/N-cadherin(+) with widespread rosette formation) within
6 days under adherent conditions, without small molecule inhibitors, and using
only minimalistic medium consisting of Dulbecco's modified Eagle's medium/F-12,
sodium bicarbonate, selenium, ascorbic acid, transferrin, and insulin (i.e., E6
medium). Furthermore, we provide evidence that the defined culture conditions
enable this high level of neural conversion in contrast to hPSCs maintained on
mouse embryonic fibroblasts (MEFs). In addition, hPSCs previously maintained on
MEFs could be rapidly converted to a neural compliant state upon transfer to
these defined conditions while still maintaining their ability to generate all
three germ layers. Overall, this fully defined and scalable protocol should be
broadly useful for generating therapeutic neural cells for regenerative
applications.
PMID- 24357016
TI - Bedside to bench: a look at experimental research with a clinical trial
checklist.
PMID- 24357015
TI - Efficacy and safety of dasatinib versus imatinib in Japanese patients with newly
diagnosed chronic-phase chronic myeloid leukemia (CML-CP): Subset analysis of the
DASISION trial with 2-year follow-up.
AB - Dasatinib is a highly potent BCR-ABL kinase inhibitor with established efficacy
and safety in imatinib-resistant or -intolerant patients with chronic myeloid
leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia.
In the global phase III DASISION trial in patients with newly diagnosed chronic
phase CML (CML-CP), dasatinib was found to have an acceptable safety profile and
demonstrated significantly faster and higher rates of complete cytogenetic
response (CCyR) and major molecular response (MMR) compared with imatinib. Here,
we report the results of a subset analysis of Japanese patients enrolled in the
DASISION trial, showing safety and efficacy profiles generally consistent with
patients enrolled worldwide, including higher response rates (CCyR, MMR) with
dasatinib compared with imatinib and similar high rates of progression-free and
overall survival with both therapies. However, the small sample size of the
present study limits the strength of these conclusions, and further exploration
is needed to confirm any differences observed in Japanese patients compared with
the total treated population. These findings support the use of dasatinib 100 mg
QD as a first-line treatment in Japanese patients with newly diagnosed CML-CP.
PMID- 24357019
TI - Extraventricular neurocytoma, a comprehensive review.
AB - AIMS AND OBJECTIVE: Extra ventricular neurocytoms (EVN) are a rare parenchymal
brain tumour distinct from central neurocytomas. This review attempts to analyze
a series of seven cases of EVN from a single institute against the background of
available literature. METHOD: Retrospective analysis of the clinical
manifestation, pathological features, imaging findings, microsurgical treatment
effectiveness and progression free survival of seven cases of EVN operated
between 2000-2012. RESULTS: The study group included five females and two males
in the age group 7-65 years (mean 30.71 yrs). The distribution of the lesion was
as follows Lobar 4, Cerebellum 1, Pineal 1, spinal 1. The duration of clinical
symptoms ranged from three months to seven years and the presentation was site
and size specific. Cystic Changes (71 %), perilesional oedema (57 %) and
heterogeneous contrast enhancement (85.7 %), and calcification (42 %) were a few
distinct imaging characteristics. Increased perfusion correlated with atypical
histology in two patients. Surgical resection remains the main management
strategy for longer outcome and patients with STR + RT and GTR had comparable
follow-up. Extremes of age and atypical histological features were adverse
prognostic factors. CONCLUSION: EVN are rare tumors with either glial or neuronal
differentiation or a potential for atypical changes. Both, GTR and STR combined
with RT, offer reasonably good outcome with overall comparable survival. The
available literature of EVN is limited, larger series with long term follow-ups
are needed to dictate the management protocol. The role of adjuvant therapy is
still debatable and needs further validation.
PMID- 24357020
TI - Nardostachys chinensis induces the differentiation of human promyelocytic
leukemic cells through the activation of the protein kinase C-dependent
extracellular signal-regulated kinase signaling pathway.
AB - The underground parts of Nardostachys chinensis (N. chinensis), which belongs the
genus Valerianaceae, have been used as sedative and analgesic agents in
traditional Korean medicine for centuries. The mitogen-activated protein kinases
(MAPKs) are serine/threonine kinases involved in the regulation of various
cellular responses, such as cell proliferation, differentiation and apoptosis.
Protein kinase C (PKC) plays a key role in the regulation of proliferation and
differentiation. In this study, we investigated the signaling pathways involved
in the differentiation of the HL-60 human leukemic cells induced by N. chinensis
extract. Treatment with N. chinensis extract resulted in the activation of the
extracellular signal-regulated kinase (ERK) pathway and induced the
differentiation of HL-60 cells into granulocytes. The activation of p38 MAPK was
also observed 24 h after treatment; however, the activation of c-Jun N-terminal
kinase (JNK) was unaffected. Treatment with an inhibitor of ERK (PD98059) blocked
the nitrotetrazolium blue chloride (NBT) reducing activity and CD11b expression
in the N. chinensis-treated HL-60 cells, whereas treatment with an inhibitor of
p38 MAPK (SB203580) had no significant effect on NBT reducing activity and CD11b
expression. In addition, N. chinensis extract increased PKC activity and the
protein levels of PKCalpha, PKCbetaI and PKCbetaII isoforms, without a
significant change in the protein levels of the PKCgamma isoform. PKC inhibitors
(GF 109203X, chelerythrine and H-7) inhibited the differentiation of HL-60 cells
into granulocytes, as well as ERK activation in the N. chinensis-treated HL-60
cells. These results indicate that the PKC and ERK signaling pathways may be
involved in the induction, by N. chinensis extract, of the differentiation of HL
60 cells into granulocytes.
PMID- 24357021
TI - A message from the new editor.
PMID- 24357022
TI - Safety and efficacy of Bixa orellana (achiote, annatto) leaf extracts.
AB - Bixa orellana leaf preparations have been used for many years by indigenous
people for a variety of medicinal applications. Published research studies in
animals indicate that various extracts of Bixa leaves exhibit antioxidant, broad
antimicrobial (antibacterial and antifungal), anti-inflammatory, analgesic,
hypoglycemic, and antidiarrheal activities. No studies have specifically assessed
the ability of leaf extracts to inhibit urogenital infections although Bixa
products have been used in folkloric medicine to treat gonorrhea and other
infections. Few human studies have been conducted and published using Bixa leaf
preparations. Many more studies have been conducted and published involving Bixa
seed (annatto) extracts than with leaf extracts. No subchronic safety (toxicity)
studies have been conducted in animals. A 6 month study in humans given 750 mg of
leaf powder per day demonstrated no significant or serious adverse effects. Bixa
leaf extracts appear to be safe when given under current conditions of use.
However, additional human and animal controlled safety and efficacy studies are
needed. In addition, detailed chemical analyses are required to establish
structure-function relationships.
PMID- 24357024
TI - Lateral ligament reconstruction with allograft in patients with severe chronic
ankle instability.
AB - INTRODUCTION: Chronic ankle instability is a condition of perception of giving
way and persistent pain usually following multiple ankle sprains. In case of
severe joint laxity, surgical treatment with reconstruction of the lateral
ligamental complex is recommended. The aim of this study was to evaluate the
functional outcome of patients treated with lateral ligament reconstruction with
allograft for severe chronic lateral ankle instability. MATERIALS AND METHODS: We
performed a retrospective cohort study of ten patients who underwent allograft
external non-anatomic ligamentoplasty for severe chronic lateral ankle
instability between 2009 and 2011, with an average follow-up of 16.3 months (SD
8.2). Median age at surgery was 29 years (range 25-35). All patients presented
both ATFL and CFL lesion. Patients were evaluated using American Orthopaedic Foot
and Ankle Society score, Karlsson-Peterson score, Tegner activity level, Sefton
stability scale, and objective examination comprehending range of motion,
anterior drawer sign and talar tilt test. Telos stress equipment was used for pre
and post-operative radiographic laxity testing. RESULTS: Follow-up examination
at an average of 16.3 months (SD 8.2) after surgery showed significant
improvement of all variables compared to pre-operative values (p < 0.001). Most
patients rated their outcome as good/excellent. Telos stress radiographs
documented improvement in joint stability. CONCLUSIONS: Lateral ligament
reconstruction with allograft represents a valid treatment option in patients
with severe chronic lateral ankle instability.
PMID- 24357025
TI - Pregnancy-associated osteoporosis with eight fractures in the vertebral column
treated with kyphoplasty and bracing: a case report.
AB - Pregnancy-associated osteoporosis is a rare condition, which imposes multiple
symptoms in the musculoskeletal system. Common complaints announced by patients
are severe pain in the lower back, hips and the joints of the lower extremities
with a reduced and less mobility status in general. Most of the patients'
problems occur in the last trimester of pregnancy or postpartum and are often not
diagnosed as side effects of osteoporosis but as problems associated with
pregnancy. Although vertebral fractures are rare complications of pregnancy
associated osteoporosis, they should be always considered in women presenting
with an acute pain syndrome in peripregnancy period. This case presents a 40-year
old primagravid woman who developed pain in hips and severe pain in the lower
back causing an immobilization diagnosed with a pregnancy-associated osteoporosis
with eight compression fractures in the thoracic and lumbar spine. Because of
sagittal imbalance of the spine, she was treated with kyphoplasty at the four
lumbar fractures and with bracing for the upper, thoracic ones, additional to the
conservative anti-osteoporotic therapy. The authors discuss pregnancy-associated
osteoporosis and its clinical presentation, as well as the indications of
kyphoplasty, spinal alignment and the risk of single conservative treatment.
PMID- 24357023
TI - Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel
sequencing of maternal plasma DNA in twin pregnancies.
AB - OBJECTIVE: The objective of this study is to assess the performance of
noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively
parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies.
METHOD: A double-blind study was performed over 12 months. A total of 189
pregnant women carrying twins were recruited from seven hospitals. Maternal
plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal
karyotype was used as gold standard to estimate the sensitivity and specificity
of sequencing-based noninvasive prenatal test. RESULTS: There were nine cases of
trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA
sequencing correctly identified nine cases of trisomy 21 and one case of trisomy
18. The discordant case of trisomy 18 was an unusual case of monozygotic twin
with discordant fetal karyotype (one normal and the other trisomy 18). The
sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy
21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively.
CONCLUSION: Our study further supported that sequencing-based noninvasive
prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high
accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis
procedures.
PMID- 24357026
TI - Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients
with late-onset multiple acyl-CoA dehydrogenase deficiency.
AB - The major cause of lipid storage myopathies (LSM) in China is multiple acyl-CoA
dehydrogenase deficiency (MADD) caused by ETFDH mutations. We here present an
analysis of the spectrum of ETFDH mutations in the largest cohort of patients
with MADD (90 unrelated patients). We identified 61 ETFDH mutations, including 31
novel mutations, which were widely distributed within the coding sequence. Three
frequent mutations were identified: c.250G > A (most common in South China),
c.770A > G and c.1227A > C (most common in both South and North China). Regional
differences of allele frequency and further haplotype analysis suggest the
possibility of founder effects of c.250G > A and c.770A > G. These findings
promise to provide the basis for implementing a rapid and economical strategy for
diagnosing MADD.
PMID- 24357029
TI - The importance of scientific peer review at SETAC.
PMID- 24357027
TI - Paradoxical effects of minocycline in the developing mouse somatosensory cortex.
AB - Minocycline, a tetracycline derivative, is known to exert neuroprotective effects
unrelated to its antimicrobial action. In particular, minocycline prevents
microglial activation in pathological conditions and consequently reduces the
production of proinflammatory factors contributing to the propagation of
diseases. Accumulative evidence indicates that microglial cells contribute to the
maturation of neuronal and synaptic networks during the normal development of the
central nervous system (CNS) and that perinatal inflammation is a known risk
factor for brain lesions. Although minocycline has been used to infer microglia
functions during development, mechanisms by which this tetracycline derivative
affect the immature CNS have not been analyzed in detail. In this study, we
demonstrate that minocycline administration during the first postnatal week of
development has paradoxical effects on microglia phenotype and on neuronal
survival in the mouse somatosensory cortex. Using a combination of
immunohistochemistry and electrophysiology, we show that intraperitoneal
injections of minocycline between postnatal days 6 and 8 affect distribution,
morphology, and functional properties of microglia cells of the whisker-related
barrel cortex, leading to the development of a phenotype resembling that of
microglia activated in pathological conditions. Minocyline also induced a massive
cell death that developed faster than changes in microglia phenotype, suggesting
that the latter is a consequence of the former. Finally, cell death and
microglial activation were not observed when minocycline treatment was postponed
by only 2 days (i.e., between postnatal days 8 and 10). These observations call
into question the use of tetracycline derivatives during CNS development to study
microglia or to reduce perinatal inflammation.
PMID- 24357031
TI - Plastics in the marine environment.
PMID- 24357032
TI - Age-related polychlorinated biphenyl dynamics in immature bull sharks
(Carcharhinus leucas).
AB - Polychlorinated biphenyls (PCBs) were quantified in liver tissues of bull sharks
(Carcharhinus leucas) ranging in age from <4 wk to >3 yr. Summed values of PCBs
(SigmaPCBs) ranged from 310 ng/g to 22 070 ng/g (lipid wt) across age classes
with SigmaPCB concentrations for the youngest sharks in the present study (<4 wk;
5230 +/- 2170 ng/g lipid wt) determined to not significantly differ from those
quantified in >3-yr-old sharks, highlighting the extent of exposure of this young
life stage to this class of persistent organic pollutants (POPs). Age
normalization of PCB congener concentrations to those measured for the youngest
sharks demonstrated a significant hydrophobicity (log octanol/water partition
coefficient [KOW ]) effect that was indicative of maternal offloading of highly
hydrophobic (log KOW >=6.5) congeners to the youngest individuals. A distinct
shift in the PCB congener profiles was also observed as these young sharks grew
in size. This shift was consistent with a transition from the maternally
offloaded signal to the initiation of exogenous feeding and the contributions of
mechanisms including growth dilution and whole-body elimination. These results
add to the growing pool of literature documenting substantially high
concentrations of POPs in juvenile sharks that are most likely attributable to
maternal offloading. Collectively, such results underscore the potential
vulnerability of young sharks to POP exposure and pose additional concerns for
shark-conservation efforts.
PMID- 24357033
TI - Effects of Cylindrospermopsis raciborskii (cyanobacteria) on the swimming
behavior of Daphnia (cladocera).
AB - The present study aimed to test the effects of raw water samples from a eutrophic
reservoir and of a saxitoxin-producing strain of Cylindrospermopsis raciborskii
on the swimming behavior of 2 key herbivore species of Daphnia. Two complementary
approaches were used, acute bioassays and behavioral assays using an automated
movement tracking system for measuring the following activity parameters:
swimming time, resting time, distance traveled, and mean velocity. In both
assays, animals were exposed to field samples or to toxic filaments in different
concentrations and observed for 2 h to 3 h. In the acute bioassays, there was a
decrease in the number of swimming individuals during the exposure period and a
recovery following removal from toxic algae. A significant relationship was found
between median effective concentration and the saxitoxin content of seston (r(2)
= 0.998; p = 0.025) in the acute bioassays with raw water samples. Behavioral
assays also showed significant effects in the activity parameters with both field
samples and the strain of C. raciborskii, with some recovery during the exposure
period. Both approaches corroborated previous research on the effects of
neurotoxic C. raciborskii on the swimming activity of Daphnia, and these effects
are compatible with the mechanism of action of saxitoxins. The present study
showed that activity parameters of aquatic organisms may be a useful tool in the
evaluation of sublethal toxicity and detection of neurotoxins in raw water.
PMID- 24357035
TI - Comparative investigation of the use of various commercial microcarriers as a
substrate for culturing mammalian cells.
AB - Microcarriers provide large adhesion area allowing high cell densities in
bioreactor systems. This study focused on the investigation of cell adhesion and
cell growth characteristics of both anchorage-dependent CHO-K1 and anchorage
independent Ag8 myeloma cell lines cultivated on four different microcarriers
(Biosilon(r), Microhex(r), Cytodex 3(r), Cytoline 2(r)) by considering the cell
kinetics and physiological data. Experiments were performed in both static and
agitated cell culture systems by using 24-well tissue culture plates and then 50
ml spinner flasks. In agitated cultures, the highest specific growth rates (0.026
h for CHO-K1 and 0.061 h for Ag8 cell line) were obtained with Cytodex 3(r) and
Cytoline 2(r) microcarriers for CHO-K1 and Ag8 cell line, respectively. Metabolic
characteristics showed some variation among the cultures with the four
microcarriers. The most significant being the higher production of lactate with
microcarriers with CHO-K1 cells relative to the Ag8 cells. SEM analyses revealed
the differences in the morphology of the cells along with microcarriers. On
Cytodex 3(r) and Cytoline 2(r), CHO-K1 cells attached to the substratum through
long, slender filopodia, whereas the cells showed a flat morphology by covering
the substratum on the Biosilon(r) and Microhex(r). Ag8 cells maintained their
spherical shapes throughout the culture for all types of microcarriers. In an
attempt to scale-up, productions were carried out in 50-ml spinner flasks.
Cytodex 3(r) (for CHO-K1 cells) and Cytoline 2(r) (for Ag8 cells) were evaluated.
The results demonstrate that high yield of biomass could be achieved through the
immobilization of the cells in each culture system. And cell cultures on
microcarriers, especially on Cytodex 3(r) and Cytoline 2(r), represented a good
potential as microcarriers for larger scale cultures of CHO-K1 and Ag8,
respectively. Moreover, owing to the fact that the cell lines and culture media
are specific, outcomes will be applicable for other clones derived from the same
host cell lines.
PMID- 24357036
TI - Development of primary cell cultures from mud crab, Scylla serrata, and their
potential as an in vitro model for the replication of white spot syndrome virus.
AB - Primary cell cultures were developed from haemocytes and testis of Scylla
serrata. Haemocytes were collected from live animals and cultured in double
strength L-15 medium (2* L-15) prepared in crab saline, supplemented with 5%
foetal bovine serum and antibiotic-antimycotic solution (penicillin 100 U/mL,
streptomycin 100 MUg/mL and amphotericin B 0.25 MUg/mL) with osmolality adjusted
to 894 mOsm/kg. The haemocytes adhered within 2 h after seeding and showed
proliferation up to 72 h. The disaggregated testis tissue fragments were seeded
in 3* L-15 supplemented with non-essential amino acid mixture, lipid concentrate
and antibiotic-antimycotic solution, with osmolality adjusted to 1,035 mOsm/kg
with crab saline. Cells from the testis could be subcultured and maintained up to
21 d as suspension culture. Different dilutions of white spot syndrome virus
(WSSV) inoculum (known virus copy number) prepared from infected Penaeus monodon
were inoculated in the cultured cells, and the cytopathic effects like
detachment, rounding of cells and clear areas of depleted cells were observed
after 48 h in haemocyte cultures. However, WSSV-exposed testis cells did not show
any obvious change until 72 h post-infection. WSSV was detected in both haemocyte
and testis cultures at different time-points of infection by conventional and
real-time PCR using WSSV-specific primers. The transcripts of WSSV were found to
be much higher in haemocytes than in testis culture. The virus harvested from the
cultured haemocytes after three passages could infect healthy P. monodon. The
present study showed that mud crab haemocyte culture can support WSSV
replication, and it can be used as an in vitro tool for WSSV replication.
PMID- 24357037
TI - Cytotoxicity evaluation of silica nanoparticles using fish cell lines.
AB - Nanoparticles (NPs) have extensive industrial, biotechnological, and
biomedical/pharmaceutical applications, leading to concerns over health risks to
humans and biota. Among various types of nanoparticles, silica nanoparticles
(SiO2 NPs) have become popular as nanostructuring, drug delivery, and optical
imaging agents. SiO2 NPs are highly stable and could bioaccumulate in the
environment. Although toxicity studies of SiO2 NPs to human and mammalian cells
have been reported, their effects on aquatic biota, especially fish, have not
been significantly studied. Twelve adherent fish cell lines derived from six
species (rainbow trout, fathead minnow, zebrafish, goldfish, haddock, and
American eel) were used to comparatively evaluate viability of cells by measuring
metabolic impairment using Alamar Blue. Toxicity of SiO2 NPs appeared to be size
, time-, temperature-, and dose-dependent as well as tissue-specific. However,
dosages greater than 100 MUg/mL were needed to achieve 24 h EC50 values
(effective concentrations needed to reduce cell viability by 50%). Smaller SiO2
NPs (16 nm) were relatively more toxic than larger sized ones (24 and 44 nm) and
external lining epithelial tissue (skin, gills)-derived cells were more sensitive
than cells derived from internal tissues (liver, brain, intestine, gonads) or
embryos. Higher EC50 values were achieved when toxicity assessment was performed
at higher incubation temperatures. These findings are in overall agreement with
similar human and mouse cell studies reported to date. Thus, fish cell lines
could be valuable for screening emerging contaminants in aquatic environments
including NPs through rapid high-throughput cytotoxicity bioassays.
PMID- 24357039
TI - Hashimoto's encephalopathy: South Korean experiences.
AB - Hashimoto's encephalopathy (HE) is a rare neurological disorder. Early diagnosis
and treatment are critical to prevent irreversible brain damage. In the present
study, we aimed to describe and classify HE on the basis of clinical,
neuroimaging, and EEG findings. We retrospectively reviewed the clinical,
radiological, and electrophysiological findings in patients who showed both
neurological symptoms and high titers of anti-thyroid antibodies, and who were
admitted between 2006 and 2012. Our patients were classified into two groups:
those presenting seizures (group 1) and those with diffuse encephalopathies
(group 2). Group 1 contained two patients. Patient 1, who showed verbal memory
disturbance, focal MRI lesions, and partial seizure activity on EEG, recovered
with antiepileptic and steroid treatments. Five of six patients assigned to group
2 were treated with steroids and showed significant improvement. One patient
treated with azathioprine showed moderate improvement. Four of these patients had
accompanying metabolic disturbances. HE is a treatable neurologic disorder with
different subtypes, each with its own clinical manifestations and treatment
options. HE can be difficult to identify and requires careful and attentive
clinical observation for diagnosis.
PMID- 24357038
TI - Aerobic exercise plus weight loss improves insulin sensitivity and increases
skeletal muscle glycogen synthase activity in older men.
AB - The purpose of this study was to determine the effects of 6-month aerobic
exercise training + weight loss (AEX + WL) on basal and insulin activation of
glycogen synthase, basal citrate synthase activity, and Akt and AS160
phosphorylation in older, overweight/obese insulin-resistant men (n = 14; 63 +/-
2 years; body mass index, 32 +/- kg/m(2)). Muscle samples of the vastus lateralis
were collected before and during a 3-hour 80 mU/m(2)/min hyperinsulinemic
euglycemic clamp. AEX + WL increased VO2max by 11% (p < .05) and decreased body
weight (-9%, p < .001). AEX + WL increased basal citrate synthase activity by 46%
(p < .01) and insulin activation of independent (2.9-fold) and fractional (2.3
fold) activities (both p < .001) of glycogen synthase. AEX + WL had no effect on
phosphorylation of Akt or AS160. Glucose utilization (M) improved 25% (p < .01),
and the change tended to be related to the increase in insulin activation of
glycogen synthase fractional activity (r = .50, p = .08) following AEX + WL. In
summary, AEX + WL has a robust effect on insulin activation of skeletal muscle
glycogen synthase activity that likely contributes to improved glucose
utilization in older insulin-resistant men.
PMID- 24357040
TI - Imaging predictors of outcome following intravenous thrombolysis in acute stroke.
AB - Intravenous tissue plasminogen activator is the only approved medical treatment
for patients with acute ischemic stroke. While it is associated with excellent
clinical outcome in about 30 %, even with timely thrombolysis administration,
certain strokes continue to evolve and lead to poor outcomes. Several studies
have attempted to identify predictors of outcome despite timely thrombolysis.
Persistence of a proximal clot burden and large vessel occlusion following
thrombolysis are markers for patients who may potentially benefit from advanced
treatment modalities like intra-arterial thrombolysis and thrombectomy. Timely
brain imaging and interpretation play a crucial role in providing these treatment
decisions. In this review, various imaging predictors of poor outcome among
patients with acute ischemic stroke treated with intravenous thrombolysis are
outlined. Despite identification of these imaging predictors, thrombolysis should
not be withheld, as it may still be beneficial in a subset of patients. Knowledge
of these predictors may set benchmarks for selecting candidates who may
potentially benefit from advanced management strategies in future trials.
PMID- 24357041
TI - Polarimetry as a tool for the study of solutions of chiral solutes.
AB - Optical rotation of aqueous solutions of D-levoglucosan was studied
experimentally in the 0.03-4.0 mol L(-1) concentration range and a nonlinear
concentration dependence of specific optical rotation (SR) was revealed.
Discontinuities observed in the concentration plot of SR (at 0.1, 0.3, 0.5, 1.0,
and 2.0 mol L(-1)) are well correlated with those found by static and dynamic
light scattering and identify concentration ranges in which different solution
domains (supramers) may exist. The average SR experimental value for a D
levoglucosan aqueous solution ([alpha]D(28) -58.5+/-8.7 deg dm(-1) cm(-3) g(-1))
was found to be in good agreement with values obtained by theoretical calculation
(TD-DFT/GIAO) of SR for 15 different conformers revealed by conformational
sampling at the PCM/B3LYP/6-311++G(2d,2p)//B3LYP/6-31+G(d,p) level, which were
shown to be strongly affected by the solvation microenvironment (0, 1, 2, and 3
explicit solvent molecules considered) due to local geometrical changes induced
in the solute molecule. This exceptionally high sensitivity of SR makes
polarimetry a unique method capable of sensing changes in the structure of
supramers detected in this study.
PMID- 24357042
TI - The impact of future expectations on adolescent sexual risk behavior.
AB - Rates of STIs, HIV, and pregnancy remain high among adolescents in the US, and
recent approaches to reducing sexual risk have shown limited success. Future
expectations, or the extent to which one expects an event to actually occur, may
influence sexual risk behavior. This prospective study uses longitudinal data
from the National Longitudinal Survey of Youth 1997 (n = 3,205 adolescents; 49.8%
female) to examine the impact of previously derived latent classes of future
expectations on sexual risk behavior. Cox regression and latent growth models
were used to determine the effect of future expectations on age at first
biological child, number of sexual partners, and inconsistent contraception use.
The results indicate that classes of future expectations were uniquely associated
with each outcome. The latent class reporting expectations of drinking and being
arrested was consistently associated with the greatest risks of engaging in
sexual risk behavior compared with the referent class, which reported
expectations of attending school and little engagement in delinquent behaviors.
The class reporting expectations of attending school and drinking was associated
with having greater numbers of sexual partners and inconsistent contraception use
but not with age at first biological child. The third class, defined by
expectations of victimization, was not associated with any outcome in adjusted
models, despite being associated with being younger at the birth of their first
child in the unadjusted analysis. Gender moderated specific associations between
latent classes and sexual risk outcomes. Future expectations, conceptualized as a
multidimensional construct, may have a unique ability to explain sexual risk
behaviors over time. Future strategies should target multiple expectations and
use multiple levels of influence to improve individual future expectations prior
to high school and throughout the adolescent period.
PMID- 24357043
TI - Management of soft tissue injuries associated with tibial plateau fractures.
AB - Tibial plateau fractures or knee fracture-dislocations often result from trauma
or sporting injuries. Given the subcutaneous position of the knee and upper
tibia, without much intervening soft tissue, any such injury can be associated
with significant soft tissue damage. Thus, consideration of the degree of soft
tissue injury must be part of the treatment plan. Specific management decisions
regarding blisters, open wounds, and compartment syndrome are discussed, as well
as the timing of surgery, role of provisional external fixation, and placement of
incisions for definitive internal fixation.
PMID- 24357044
TI - Surgical approaches for tibial plateau fractures.
AB - Tibial plateau fractures are common yet complex injuries, and include a wide
variety of fracture patterns. They are also potentially associated with
significant soft tissue injury. Thus, the surgeon preparing to operate on one of
these fractures must choose from a variety of surgical approaches that have been
described. The choice of approach is dictated principally by the fracture
pattern, with consideration of the soft tissue envelope, patient factors, and
associated injuries. Occasionally, associated intra-articular injuries may also
need to be addressed. Commonly used approaches to the proximal tibia, which
together allow for the treatment of any proximal tibia fracture, will be
described in this article.
PMID- 24357045
TI - Hal Oscar Anger, D.Sc. (hon.) (1920-2005): a pioneer in nuclear medicine
instrumentation.
PMID- 24357046
TI - Negative pressure wound therapy in head and neck surgery.
AB - IMPORTANCE Negative pressure wound therapy has been shown to accelerate healing.
There is a paucity of literature reporting its use as a tool to promote wound
healing in head and neck reconstruction. OBJECTIVE To review 1 institution's
experience with negative pressure dressings to further describe the indications,
safety, and efficacy of this technique in the head and neck. DESIGN, SETTING, AND
PARTICIPANTS Retrospective case series at a tertiary care academic hospital. One
hundred fifteen patients had negative pressure dressings applied between April
2005 and December 2011. Data were gathered, including indications, details of
negative pressure dressing use, adverse events, wound healing results, potential
risk factors for compromised wound healing (defined as previous radiation
therapy, hypothyroidism, or diabetes mellitus), and wound characteristics
(complex wounds included those with salivary contamination, bone exposure, great
vessel exposure, in the field of previous microvascular free tissue transfer, or
in the case of peristomal application in laryngectomy). EXPOSURE Negative
pressure wound therapy utilized after head and neck reconstruction. MAIN OUTCOMES
AND MEASURES Indications for therapy, length and number of dressing applications,
identification of wound healing risk factors, classification of wound complexity,
wound healing results, and adverse events related to the use of the device.
RESULTS Negative pressure wound therapy was used primarily for wounds of the neck
(94 of 115 patients [81.7%]) in addition to other head and neck locations (14 of
115 patients [12.2%]), and free tissue transfer donor sites (7 of 115 patients
[6.1%]). The mean (SD) wound size was 5.6 (5.0) cm. The mean number of negative
pressure dressing applications was 1.7 (1.2), with an application length of 3.7
(1.4) days. Potential risk factors for compromised wound healing were present in
82 of 115 patients (71.3%). Ninety-one of 115 patients (79.1%) had complex
wounds. Negative pressure dressings were used in wounds with salivary
contamination (n = 64), bone exposure (n = 40), great vessel exposure (n = 25),
previous free tissue transfer (n = 55), and peristomal application after
laryngectomy (n = 32). Adverse events occurred in 4 of 115 patients (3.5%).
CONCLUSIONS AND RELEVANCE Negative pressure wound therapy in head and neck
surgery is safe and has potential to be a useful tool for complex wounds in
patients with a compromised ability to heal. LEVEL OF EVIDENCE 4.
PMID- 24357048
TI - Phospholipase C epsilon-1 inhibits p53 expression in lung cancer.
AB - The pathogenesis of lung cancer is to be further investigated. Recent reports
indicate that phospholipase C epsilon-1 (PLCE1) is a critical molecule involved
in tumour growth. This study aims to investigate the role of PLCE1 in the
regulation of apoptosis in lung cancer cells. In this study, the surgically
removed non-small-cell lung cancer (NSCLC) tissue was collected from 36 patients.
Single NSCLC cells were prepared from the tissue, in which immune cells of CD3(+)
, CD11c(+) , CD19(+) , CD68(+) and CD14(+) were eliminated by magnetic cell
sorting. The expression of PLCE1 and p53 was assessed by quantitative real-time
polymerase chain reaction and Western blotting. Apoptosis of NSCLC cells was
analysed by flow cytometry. The results showed that, in cultured NSCLC cells,
high levels of PLCE1 and low levels p53 were detected; the two molecules showed a
negative correlation (p < 0.01). The addition of anti-PLCE1 antibody increased
the expression of p53 in NSCLC cells, which increased the frequency of apoptotic
NSCLC cells. We conclude that NSCLC cells express high levels of PLCE1, which
suppresses the expression of p53 in NSCLC cells. PLCE1 can be a therapeutic
target of NSCLC.
PMID- 24357047
TI - Effects of dried plum supplementation on bone metabolism in adult C57BL/6 male
mice.
AB - Dietary supplementation of dried plum (DP) prevents bone loss and restores bone
mass in osteopenic animal models. This study was designed to determine the
effects of DP supplementation on bone metabolic activity over time using adult (6
month-old) male C57BL/6 mice (n = 40) receiving control (CON = AIN93 M) or CON+DP
25 % (w/w) diets for 4 or 12 weeks. After 4 weeks of treatment, animals consuming
the DP diet had a higher whole-body bone mineral density, vertebral trabecular
bone volume (BV/TV), and femoral cortical thickness compared to the CON animals.
In the distal metaphysis of the femur, BV/TV was increased in the DP-treated
animals, but only after 12 weeks. Bone histomorphometric analyses revealed that
DP decreased osteoblast surface (67 %) and osteoclast surface (62 %) at 4 weeks,
but these surfaces normalized to the CON animals by 12 weeks. Coincident with
these changes, the mineralizing surface (MS/BS) and cancellous bone formation
rate (BFR/BS) were reduced at 4 weeks in the DP group compared to the CON, but by
12 weeks of DP supplementation, BFR/BS (~twofold) and MS/BS (~1.7-fold) tended to
be increased (p < 0.10). The relative abundance of RNA for key regulators of
osteoblast and osteoclast differentiation and indicators of osteoblast activity
were reduced in the DP group at 4 weeks with no difference between groups at 12
weeks. These results indicate that supplementing the diet with DP initially
suppressed cancellous bone turnover, but a biphasic response occurs over time,
resulting in a positive effect on bone mass and structure.
PMID- 24357049
TI - The longitudinal age and birth cohort trends of smoking in Sweden: a 24-year
follow-up study.
AB - OBJECTIVES: The aim of this study is to analyse longitudinally, the annual
effects of age group and birth cohort on smoking in the Swedish population during
a 24-year period and to analyse the smoking trends for different levels of
education. METHODS: A random sample of adult, non-institutionalized persons aged
16-71 years was interviewed every 8 years by professional interviewers. In
addition to three time-related variables--year of interview, age at the time of
the interview, and year of birth--we included the following explanatory variables
in the analyses: sex, educational level, and urbanization. RESULTS: We found
significant decreases in smoking prevalence in all studied subgroups. The
adjusted odds ratios for age were 0.89 (95 % CI 0.88-0.90) and 0.92 (95 % CI 0.91
0.93) for men and women, respectively. The decreases in smoking over time were
significant in all levels of education, except for in women with low educational
level. CONCLUSIONS: In Sweden, the prevalence of smoking has decreased in most
age groups and cohorts, and in persons in most levels of education, albeit less
so in women with low educational level.
PMID- 24357050
TI - A long-term prospective follow-up study of incident RLS in the course of chronic
DAergic therapy in newly diagnosed untreated patients with Parkinson's disease.
AB - It is currently controversial if and in which terms Parkinson's disease (PD) and
restless legs syndrome (RLS) are linked in co-morbid association. In a cohort of
106 de novo PD patients (67 male and 39 female, aged 42-83 years), 15 of them
developed RLS, which was prospectively assessed at 6-month intervals from the
starting of dopamine(DA)ergic therapy. The incidence rate of total RLS was 47 per
1,000 case/person per year and 37 per 1,000 case/person per year after the
exclusion of possible "secondary" forms of the disorder (n = 3). These figures
are higher than those reported in an incidence study conducted in German general
population (Study of Health in Pomerania), in which the method of ascertainment
of RLS similar to ours has been used. An incidence rate of total RLS
significantly higher than that reported in the above-mentioned study was found in
the age ranges 55-64 years and in the age range 45-74 years standardized to
European general population 2013 (70 and 53 per 1,000 case/person per year,
respectively, p < 0.01). Ten out of 12 patients (83.3 %) developed RLS within 24
months from the starting of DAergic medication (median latency 7.5 months). These
findings support the view that sustained DAergic therapy could represent the
critical factor inducing an increased incidence of RLS in patients with PD and
that the latter disease should be regarded as the condition predisposing to the
occurrence of the former and not viceversa as previously hypothesized. The
mechanism underlying the increased incidence of RLS remains unclear and deserves
further investigation.
PMID- 24357052
TI - Botulinum toxin in myotonia congenita: it does not help against rigidity and
pain.
AB - Botulinum toxin (BT) is a potent local muscle relaxant with analgetic properties.
Myotonia congenita (MC) is a genetic disorder producing muscle rigidity and pain.
BT injected into the trapezius produced mild paresis, but no effect on rigidity
and pain. There were no signs of systemic effects. Lack of BT efficacy on MC
rigidity confirms its origin from muscle membrane dysfunction rather than from
inappropriate neuromuscular activation. Lack of BT efficacy on pain could be
caused by lack of anti-rigidity effect. It could also be due to separate non
muscular pain mechanisms unresponsive to BT.
PMID- 24357053
TI - Elastin-derived peptides potentiate atherosclerosis through the immune Neu1
PI3Kgamma pathway.
AB - AIMS: Elastin is degraded during vascular ageing and its products, elastin
derived peptides (EP), are present in the human blood circulation. EP binds to
the elastin receptor complex (ERC) at the cell surface, composed of elastin
binding protein (EBP), a cathepsin A and a neuraminidase 1. Some in vitro
functions have clearly been attributed to this binding, but the in vivo
implications for arterial diseases have never been clearly investigated. METHODS
AND RESULTS: Here, we demonstrate that chronic doses of EP injected into mouse
models of atherosclerosis increase atherosclerotic plaque size formation. Similar
effects were observed following an injection of a VGVAPG peptide, suggesting that
the ERC mediates these effects. The absence of phosphoinositide 3-kinase gamma
(PI3Kgamma) in bone marrow-derived cells prevented EP-induced atherosclerosis
development, demonstrating that PI3Kgamma drive EP-induced arterial lesions.
Accordingly, in vitro studies showed that PI3Kgamma was required for EP-induced
monocyte migration and ROS production and that this effect was dependent upon
neuraminidase activity. Finally, we showed that degradation of elastic lamellae
in LDLR(-/-) mice fed an atherogenic diet correlated with atherosclerotic plaque
formation. At the same time, the absence of the cathepsin A-neuraminidase 1
complex in cells of the haematopoietic lineage abolished atheroma plaque size
progression and decreased leucocytes infiltration, clearly demonstrating the role
of this complex in atherogenesis and suggesting the involvement of endogenous EP.
CONCLUSION: Altogether, this work identifies EP as an enhancer of atherogenesis
and defines the Neuraminidase 1/PI3Kgamma signalling pathway as a key mediator of
this function in vitro and in vivo.
PMID- 24357051
TI - The potential of biomarkers in psychiatry: focus on proteomics.
AB - The etiology and pathogenesis of many psychiatric disorders are unclear with many
signaling pathways and complex interactions still unknown. Primary information
provided from gene expression or brain activity imaging experiments is useful,
but can have limitations. There is a current effort focusing on the discovery of
diagnostic and prognostic proteomic potential biomarkers for psychiatric
disorders. Despite this work, there is still no biological diagnostic test
available for any mental disorder. Biomarkers may advance the care of psychiatric
illnesses and have great potential to knowledge of psychiatric disorders but
several drawbacks must be considered. Here, we describe the potential of
proteomic biomarkers for better understanding and diagnosis of psychiatric
disorders and current putative biomarkers for schizophrenia, depression, autism
spectrum disorder and attention deficit/hyperactivity disorder.
PMID- 24357054
TI - Simultaneous MRI of lung structure and perfusion in a single breathhold.
AB - PURPOSE: To develop and demonstrate a breathheld 3D radial ultrashort echo time
(UTE) acquisition to visualize co-registered lung perfusion and vascular
structure. MATERIALS AND METHODS: Nine healthy dogs were scanned twice at 3 Tesla
(T). Contrast-enhanced pulmonary perfusion scans were acquired with a temporally
interleaved three-dimensional (3D) radial UTE (TE = 0.08 ms) sequence in a
breathhold (1 s time frames over a 33 s breathhold). The 3D breathheld volume was
reconstructed into time-resolved perfusion datasets, and a composite vascular
structure dataset. For structural comparison, a 5 min respiratory-gated 3D radial
UTE scan was acquired. Data were analyzed by quantitative metrics and radiologist
scoring. RESULTS: Appropriate time-course of contrast was seen in all subjects.
Right ventricle to aorta transit times were 7.4 +/- 2.0 s. Relative lung
enhancement was a factor of 8.4 +/- 1.5. Radiologist scoring showed similarly
excellent visualization of the pulmonary arteries to the subsegmental level in
breathheld (94% of cases) and respiratory-gated (100% of cases) acquisitions (P =
0.33) despite the aggressive under sampling in the breathheld scan. Similarly,
differentiation of lung tissue and airways was achieved by both acquisition
methods. CONCLUSION: A time-resolved 3D radial UTE sequence for simultaneous
imaging of pulmonary perfusion and co-registered vascular structure is feasible.
PMID- 24357055
TI - Bone metastases in hepatocellular carcinoma: an emerging issue.
AB - The nature and the characteristics of bone metastases (BMs) in hepatocellular
carcinoma (HCC) have not been fully explored in literature, presumably because
HCC skeletal involvement was rarely diagnosed until a few years ago. Recently,
the prognosis and the management of HCC clinical progression have been improved
thanks to novel imaging techniques and multidisciplinary treatment approaches. As
in other osteotropic cancers, both angiogenesis and the epithelial-to-mesenchymal
transition play a crucial role in skeletal colonization, with the cooperation of
additional factors including vascular endothelial growth factor, transforming
growth factor beta, platelet-derived growth factor, insulin-like growth factors I
and II, bone morphogenetic proteins, secretory protein clusterin, and others. BMs
from HCC are often characterized by soft-tissue expansion with an abundant
vascular component and elevated tumor burden. As the majority of metastatic bone
lesions from HCC are osteolytic, they are detectable by computerized tomography
only at a late stage and not usually visualized by traditional bone scintigraphy.
For this reason, new imaging tools are currently being investigated, such as dual
tracer positron emission computerized tomography. HCC is frequently complicated
by liver failure, resulting in a lower tolerance to opioids used for pain
control, but radiotherapy and other local-regional treatments are useful in the
treatment of BMs from HCC.
PMID- 24357056
TI - Ovarian cancer microenvironment: implications for cancer dissemination and
chemoresistance acquisition.
AB - Ovarian adenocarcinoma is characterized by a late detection, dissemination of
cancer cells into the whole peritoneum, and the frequent acquisition of
chemoresistance. If these particularities can be explained in part by intrinsic
properties of ovarian cancer cells, an increased number of studies show the
importance of the tumor microenvironment in tumor progression. Ovarian cancer
cells can regulate the composition of their stroma in promoting the formation of
ascitic fluid, rich in cytokines and bioactive lipids, and in stimulating the
differentiation of stromal cells into a pro-tumoral phenotype. In return, cancer
associated fibroblasts, cancer-associated mesenchymal stem cells, tumor
associated macrophages, or other peritoneal cells, such as adipocytes and
mesothelial cells can regulate tumor growth, angiogenesis, dissemination, and
chemoresistance. This review focuses on the current knowledge about the roles of
stromal cells and the associated secreted factors on tumor progression. We also
summarize the different studies showing that targeting the microenvironment
represents a great potential for improving the prognosis of patients with ovarian
adenocarcinoma.
PMID- 24357057
TI - Gastroenteropancreatic neuroendocrine tumors: current perspectives and future
challenges.
PMID- 24357058
TI - Cystathionine gamma-lyase accelerates osteoclast differentiation: identification
of a novel regulator of osteoclastogenesis by proteomic analysis.
AB - OBJECTIVE: Clinical evidence has linked vascular calcification in advanced
atherosclerotic plaques with overt cardiovascular disease and mortality. Bone
resorbing monocyte-derived osteoclast-like cells are sparse in these plaques,
indicating that their differentiation capability could be suppressed. Here, we
seek to characterize the process of osteoclastogenesis by identifying novel
regulators and pathways, with the aim of exploring possible strategies to reduce
calcification. APPROACH AND RESULTS: We used a quantitative mass spectrometry
strategy, tandem mass tagging, to quantify changes in the proteome of osteoclast
like cells differentiated from RAW264.7 cells in response to, receptor activator
of nuclear factor kappa-B ligand induction, a common in vitro model for
osteogenesis. More than 4000 proteins were quantified, of which 138 were
identified as novel osteoclast-related proteins. We selected 5 proteins for
subsequent analysis (cystathionine gamma-lyase [Cth/CSE], EGF-like repeat and
discoidin I-like domain-containing protein 3, integrin alpha FG-GAP repeat
containing 3, adseverin, and serpinb6b) and show that gene expression levels are
also increased. Further analysis of the CSE transcript profile reveals an early
onset of an mRNA increase. Silencing of CSE by siRNA and dl-propargylglycine, a
CSE inhibitor, attenuated receptor activator of nuclear factor kappa-B ligand
induced tartrate-resistant acid phosphatase type 5 activity and pit formation,
suggesting that CSE is a potent inducer of calcium resorption. Moreover,
knockdown of CSE suppressed expression of osteoclast differentiation markers.
CONCLUSIONS: Our large-scale proteomics study identified novel candidate
regulators or markers for osteoclastogenesis and demonstrated that CSE may act in
early stages of osteoclastogenesis.
PMID- 24357059
TI - Insulin-regulated protein palmitoylation impacts endothelial cell function.
AB - OBJECTIVE: Defects in insulin signaling are associated with abnormal endothelial
cell function, which occurs commonly in cardiovascular disease. Targets of
insulin signaling in endothelial cells are incompletely understood. Protein S
palmitoylation, the reversible modification of proteins by the lipid palmitate,
is a post-translational process relevant to cell signaling, but little is known
about the role of insulin in protein palmitoylation. APPROACH AND RESULTS: To
test the hypothesis that insulin alters protein palmitoylation in endothelial
cells, we combined acyl-biotin exchange chemistry with stable isotope labeling by
amino acids in cell culture to perform quantitative proteomic profiling of human
endothelial cells. We identified ~380 putative palmitoylated proteins, of which
>200 were not known to be palmitoylated; ~10% of the putative palmitoylated
proteins were induced or suppressed by insulin. Of those potentially affected by
insulin, <10 have been implicated in vascular function. For one, platelet
activating factor acetylhydrolase IB subunit gamma (PAFAH1b3; not previously
known to be palmitoylated), we confirmed that insulin stimulated palmitoylation
without affecting PAFAH1b3 protein abundance. Chemical inhibition of
palmitoylation prevented insulin-induced angiogenesis in vitro; knockdown of
PAFAH1b3 had the same effect. PAFAH1b3 knockdown also disrupted cell migration.
Mutagenesis of cysteines at residues 56 and 206 prevented palmitoylation of
PAFAH1b3, abolished its capacity to stimulate cell migration, and inhibited its
association with detergent-resistant membranes, which are implicated in cell
signaling. Insulin promoted the association of wild-type PAFAH1b3 with detergent
resistant membranes. CONCLUSIONS: These findings provide proof of principle for
using proteomics to identify novel insulin-inducible palmitoylation targets
relevant to endothelial function.
PMID- 24357060
TI - Novel lipid droplet-associated serine hydrolase regulates macrophage cholesterol
mobilization.
AB - OBJECTIVE: Lipid-laden macrophages or foam cells are characterized by massive
cytosolic lipid droplet (LD) deposition containing mostly cholesterol ester (CE)
derived from the lipoproteins cleared from the arterial wall. Cholesterol efflux
from foam cells is considered to be atheroprotective. Because cholesterol is
effluxed as free cholesterol, CE accumulation in LDs may limit free cholesterol
efflux. Our objective was to identify proteins that regulate cholesterol
trafficking through LDs. APPROACH AND RESULTS: In a proteomic analysis of the LD
fraction of RAW 264.7 macrophages, we identified an evolutionarily conserved
protein with a canonical GXSXG lipase catalytic motif and a predicted alpha/beta
hydrolase fold, the RIKEN cDNA 1110057K04 gene, which we named LD-associated
hydrolase (LDAH). LDAH association with LDs was confirmed by immunoblotting and
immunocytochemistry. LDAH was labeled with a probe specific for active serine
hydrolases. LDAH showed relatively weak in vitro CE hydrolase activity. However,
cholesterol measurements in intact cells supported a significant role of LDAH in
CE homeostasis because LDAH upregulation and downregulation decreased and
increased, respectively, intracellular cholesterol and CE in human embryonic
kidney-293 cells and RAW 264.7 macrophages. Mutation of the putative nucleophilic
serine impaired active hydrolase probe binding, in vitro CE hydrolase activity,
and cholesterol-lowering effect in cells, whereas this mutant still localized to
the LD. LDAH upregulation increased CE hydrolysis and cholesterol efflux from
macrophages, and, interestingly, LDAH is highly expressed in macrophage-rich
areas within mouse and human atherosclerotic lesions. CONCLUSIONS: The data
identify a candidate target to promote reverse cholesterol transport from
atherosclerotic lesions.
PMID- 24357061
TI - Associations between dietary patterns and skin microcirculation in healthy
subjects.
AB - OBJECTIVE: Microvascular dysfunction is suggested to be a marker of common
pathophysiological mechanisms in the development of insulin resistance,
cardiovascular diseases, and type 2 diabetes mellitus. Given the established
relationship of diet with the macrovascular disease, the aim of this study was to
investigate for the first time the possible associations between dietary patterns
and microcirculation. APPROACH AND RESULTS: Two hundred ninety-one healthy men
and women selected from the Supplementation en Vitamines et Mineraux Antioxydants
2' cohort were assessed for anthropometric, nutritional, biochemical, and
microcirculation parameters using finger skin capillaroscopy. Dietary intake was
assessed cross-sectionally using a food frequency questionnaire, and principal
component analysis was used to identify dietary patterns from 40 food groups. Six
dietary patterns were identified. A dietary pattern characterized by increased
consumption of vegetable oils, poultry, and fish and seafood was positively
associated with both functional and anatomic capillary density after adjusting
for confounders (beta=0.13, P=0.05 and beta=0.20, P=0.00, respectively). A second
dietary pattern with increased consumption of sweets was inversely associated
with functional and anatomic capillary density in all multivariate models (beta=
0.14, P=0.03 and beta=-0.17, P=0.01). There were no associations between any of
the derived dietary patterns and capillary recruitment. CONCLUSIONS: In healthy
subjects, a dietary pattern characterized by an increased consumption of
vegetable oils, poultry, and fish and seafood and low consumption of sweets was
associated with better microvascular function. Further prospective studies are
needed to confirm the present association.
PMID- 24357062
TI - Inhibition of arthritis in the Lewis rat by apolipoprotein A-I and reconstituted
high-density lipoproteins.
AB - OBJECTIVE: This study questions whether high-density lipoproteins (HDLs) and
apolipoprotein A-I inhibit joint inflammation in streptococcal cell wall
peptidoglycan-polysaccharide (PG-PS)-induced arthritis in female Lewis rats.
APPROACH AND RESULTS: Administration of PG-PS to female Lewis rats caused acute
joint inflammation after 4 days, followed by remission by day 8. The animals
subsequently developed chronic joint inflammation that persisted until euthanasia
at day 21. Treatment with apolipoprotein A-I 24 hours before and 24 hours after
PG-PS administration reduced the acute and chronic joint inflammation. Treatment
with apolipoprotein A-I at days 7, 9, and 11 after PG-PS administration reduced
the chronic joint inflammation. Treatment with apolipoprotein A-I or
reconstituted HDLs consisting of apolipoprotein A-I complexed with
phosphatidylcholine 24 hours before and at days 1, 7, 9, and 11 after PG-PS
administration reduced acute and chronic joint inflammation. Treatment with
apolipoprotein A-I also reduced the inflammatory white blood cell count, synovial
fluid proinflammatory cytokine levels, synovial tissue macrophage accumulation,
as well as toll-like receptor 2, and inflammatory cytokine expression. At the
molecular level, preincubation of human monocyte-derived macrophages with
apolipoprotein A-I or reconstituted HDLs before PG-PS stimulation inhibited the
PG-PS-induced increase in toll-like receptor 2 and myeloid differentiation
primary response gene (88) mRNA levels, nuclear factor-kappaB activation, and
proinflammatory cytokine production. The effects of apolipoprotein A-I and
reconstituted HDLs were abolished by transfecting the human monocyte-derived
macrophages with ATP-binding cassette transporter A1 or G1 siRNA. CONCLUSIONS:
Apolipoprotein A-I and reconstituted HDLs attenuate PG-PS-induced arthritis in
the rat. Studies in human monocyte-derived macrophages indicate that this benefit
may be because of the inhibition of toll-like receptor 2 expression and decreased
nuclear factor-kappaB activation in macrophages.
PMID- 24357063
TI - Carboxyl terminus of ADAMTS13 directly inhibits platelet aggregation and ultra
large von Willebrand factor string formation under flow in a free-thiol-dependent
manner.
AB - OBJECTIVE: ADAMTS13 (A Disintegrin And Metalloprotease with Thrombospondin type 1
repeats, 13) cleaves von Willebrand factor (VWF), thereby inhibiting thrombus
formation. Proteolytic cleavage relies on the amino-terminal (MDTCS) domains, but
the role of the more distal carboxyl-terminal domains of ADAMTS13 is not fully
understood. A previous study demonstrated the presence of multiple surface
exposed free sulfhydryls on ADAMTS13 that seemed to interact with those on VWF
under shear. Here, we determined the physiological relevance of such an
interaction in antithrombotic responses under flow. APPROACH AND RESULTS: A
microfluidic assay demonstrated that a carboxyl-terminal fragment of ADAMTS13,
comprising either 2 to 8 thrombospondin type 1 (TSP1) repeats and CUB domains
(T2C) or 5 to 8 Thrombospondin type 1 (TSP1) repeats and CUB domains (T5C),
directly inhibited platelet adhesion/aggregation on a collagen surface under
arterial shear. In addition, an intravital microscopic imaging analysis showed
that the carboxyl-terminal fragment of ADAMTS13 (T2C or T5C) was capable of
inhibiting the formation and elongation of platelet-decorated ultra large (UL)
VWF strings and the adhesion of platelets/leukocytes on endothelium in mesenteric
venules after oxidative injury. The inhibitory activity of T2C and T5C on
platelet aggregation and ULVWF string formation were dependent on the presence of
their surface free thiols; pretreatment of T2C and T5C or full-length ADAMTS13
with N-ethylmaleimide that reacts with free sulfhydryls abolished or
significantly reduced its antithrombotic activity. CONCLUSIONS: Our results
demonstrate for the first time that the carboxyl terminus of ADAMTS13 has direct
antithrombotic activity in a free-thiol-dependent manner. The free thiols in the
carboxyl-terminal domains of ADAMTS13 may also contribute to the overall
antithrombotic function of ADAMTS13 under pathophysiological conditions.
PMID- 24357065
TI - Sarcopenia is a prognostic factor in living donor liver transplantation.
AB - The aims of this study were to investigate sarcopenia as a novel predictor of
mortality and sepsis after living donor liver transplantation (LDLT) and to
evaluate the effects of early enteral nutrition on patients with sarcopenia. Two
hundred four patients undergoing preoperative computed tomography within the
month before LDLT were retrospectively evaluated. The lengths of the major and
minor axes of the psoas muscle were simply measured at the caudal end of the
third lumbar vertebra, and the area of the psoas muscle was calculated. A psoas
muscle area lower than the 5th percentile for healthy donors of each sex was
defined as sarcopenia. Ninety-six of the 204 patients (47.1%), including 58.3%
(60/103) of the male patients and 35.6% (36/101) of the female patients, were
diagnosed with sarcopenia. Sarcopenia was independently and significantly
associated with overall survival: there was an approximately 2-fold higher risk
of death for patients with sarcopenia versus patients without sarcopenia (hazard
ratio = 2.06, P = 0.047). Sarcopenia was an independent predictor of
postoperative sepsis (hazard ratio = 5.31, P = 0.009). Other independent
predictors were a younger recipient age (P < 0.001) and a higher body mass index
(P = 0.02). Early enteral nutrition within the first 48 hours after LDLT was
performed for 24.2% in 2003-2007 and for 100% in 2008-2011, and the incidence of
postoperative sepsis for patients with sarcopenia (n = 96) was 28.2% (11/39) in
2003-2007 and 10.5% (6/57) in 2008-2011 (P = 0.03). In conclusion, sarcopenia is
an independent predictor of mortality and sepsis after LDLT. The incidence of
postoperative sepsis was reduced even in patients with sarcopenia after the
routine application of early enteral nutrition.
PMID- 24357064
TI - Spino-olivary projections in the rat are anatomically separate from postsynaptic
dorsal column projections.
AB - The gracile nucleus (GN) and lateral part of rostral dorsal accessory olive
(rDAO) are important relays for indirect, postsynaptic dorsal column, and direct
ascending pathways, respectively, that terminate as climbing fibers in the
"hindlimb-receiving" parts of the C1 and C3 zones in the cerebellar cortex. While
the spinal cells of origin of that project to GN and rDAO are from largely
separate territories in the spinal cord, previous studies have indicated that
there could be an area of overlap between these two populations in the medial
dorsal horn. Given the access of these two ascending tracts to sensory (thalamic)
versus sensorimotor (precerebellar) pathways, the present study therefore
addresses the important question of whether or not individual neurons have the
potential to contribute axons to both ascending pathways. A double-fluorescent
tracer strategy was used in rats (red Retrobeads and Fluoro-Ruby or green
Retrobeads and Fluoro-Emerald) to map the spatial distribution of cells of origin
of the two projections in the lumbar spinal cord. The two pathways were found to
receive input from almost entirely separate territories within the lumbar cord
(levels L3-L5). GN predominantly receives input from lamina IV, while rDAO
receives its input from three cell populations: medial laminae V-VI, lateral
lamina V, and medial laminae VII-VIII. Cells that had axons that branched to
supply both GN and rDAO represented only about 1% of either single-labeled cell
population. Overall, the findings therefore suggest functional independence of
the two ascending pathways.
PMID- 24357067
TI - Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the
inflammatory response of resident and peripheral immune cells and by suppressing
remyelination.
AB - Astrocytes respond to insult with a process of cellular activation known as
reactive astrogliosis. One of the key signals regulating this phenomenon is the
transcription factor nuclear factor-kappa B (NF-kappaB), which is responsible for
modulating inflammation, cell survival, and cell death. In astrocytes, following
trauma or disease, the expression of NF-kappaB-dependent genes is highly
activated. We previously demonstrated that inactivation of astroglial NF-kappaB
in vivo (GFAP-IkappaBalpha-dn mice) leads to improved functional outcome in
experimental autoimmune encephalomyelitis (EAE), and this is accompanied by
reduction of pro-inflammatory gene expression in the CNS. Here we extend our
studies to show that recovery from EAE in GFAP-IkappaBalpha-dn mice is associated
with reduction of peripheral immune cell infiltration into the CNS at the chronic
phase of EAE. This is not dependent on a less permeable blood-brain barrier, but
rather on a reduced immune cell mobilization from the periphery. Furthermore,
once inside the CNS, the ability of T cells to produce pro-inflammatory cytokines
is diminished during acute disease. In parallel, we found that the number of
total and activated microglial cells is reduced, suggesting that functional
improvement in GFAP-IkappaBalpha-dn mice is dependent upon reduction of the
overall inflammatory response within the CNS sustained by both resident and
infiltrating cells. This results in preservation of myelin compaction and
enhanced remyelination, as shown by electron microscopy analysis of the spinal
cord. Collectively our data indicate that astrocytes are key players in driving
CNS inflammation and are directly implicated in the pathophysiology of EAE, since
blocking their pro-inflammatory capability results in protection from the
disease.
PMID- 24357068
TI - Function of Jam-B/Jam-C interaction in homing and mobilization of human and mouse
hematopoietic stem and progenitor cells.
AB - The junctional adhesion molecules Jam-b and Jam-c interact together at
interendothelial junctions and have been involved in the regulation of immune
response, inflammation, and leukocyte migration. More recently, Jam-c has been
found to be expressed by hematopoietic stem and progenitor cells (HSPC) in mouse.
Conversely, we have reported that Jam-b is present on bone marrow stromal cells
and that Jam-b-deficient mice have defects in the regulation of hematopoietic
stem cell pool. In this study, we have addressed whether interaction between Jam
b and Jam-c participates to HSPC mobilization or hematopoietic reconstitution
after irradiation. We show that a blocking monoclonal antibody directed against
Jam-c inhibits hematopoietic reconstitution, progenitor homing to the bone
marrow, and induces HSPC mobilization in a Jam-b dependent manner. In the latter
setting, antibody treatment over a period of 3 days does not alter hematopoietic
differentiation nor induce leukocytosis. Results are translated to human
hematopoietic system in which a functional adhesive interaction between JAM-B and
JAM-C is found between human HSPC and mesenchymal stem cells. Such an interaction
does not occur between HSPC and human endothelial cells or osteoblasts. It is
further shown that anti-JAM-C blocking antibody interferes with CD34(+)
hematopoietic progenitor homing in mouse bone marrow suggesting that monoclonal
antibodies inhibiting JAM-B/JAM-C interaction may represent valuable therapeutic
tools to improve stem cell mobilization protocols.
PMID- 24357069
TI - Natural cycle IVF: evaluation of 463 cycles and summary of the current
literature.
AB - PURPOSE: Natural cycle (NC) IVF/ICSI has proven to be an alternative to
conventional IVF/ICSI cycles. METHODS: Within our retrospective, observational
study (n = 159) infertile couples underwent (n = 463) cycles of NC-IVF/ICSI from
May 2007 until December 2011. Oocyte pick-up was performed within a pure natural
cycle excluding any hormonal stimulation except of hCG for ovulation induction.
Oocytes were fertilized by IVF/ICSI and embryo transfer took place 2 or 3 days
later. In addition, the current literature was analysed concerning pregnancy
rates in NC-IVF/ICSI cycles. RESULTS: Oocyte pick-up was performed in n = 463 NC
and was successful in n = 342 cases (IVF n = 135, ICSI n = 207). 203 oocytes were
fertilized (IVF n = 87, ICSI n = 116, FR 59.4 %) and lead to 192 embryo
transfers. Finally, 25 pregnancies were reached (PR 13.0 % per transfer)
resulting in four biochemical pregnancies, 7 (33.3 %) miscarriages, one pregnancy
of unknown outcome and 13 live births. Within the current literature (n = 27
studies), PR in NC-IVF/ICSI cycles varied between 10.2 and 50 %. CONCLUSIONS:
Within our study, pregnancy rates in pure NC-IVF/ICSI remained below 15 %.
Although this may be linked to unfavourable preconditions like patients' age >40
years, low ovarian reserve or long duration of infertility, further improvement
is necessary to increase pregnancy rates.
PMID- 24357070
TI - Dissociated language functions: a matter of atypical language lateralization or
cerebral plasticity?
AB - BACKGROUND AND STUDY AIMS: The left hemisphere is generally considered to harbor
language functions. Atypical cortical language lateralization is mainly
demonstrated in left-handed and ambidextrous individuals, whereas dissociated
language functions have been reported in association with brain injuries as a
part of the reorganization process. We present a thoughtful discussion on the
underlying mechanisms of dissociated language functions through an illustrative
case of dissociated expressive language. CASE REPORT: A 31-year-old left-handed
woman presented with a recurrent left frontal glioma. Preoperative language
functional magnetic resonance imaging (fMRI) panel revealed right-sided dominance
for two different language tasks (verbal fluency and visual naming), and the word
chain task demonstrated maximal activation in the left hemisphere at the
posterior margin of the tumor. The patient was operated on awake to assess
language functions intraoperatively. Preoperative fMRI findings were confirmed
revealing a task-specific dissociation of expressive language functions. Surgical
resection was taken to the functional boundaries. Postoperatively, no language
dysfunction occurred. CONCLUSIONS: Dissociated language functions are prone to
occur in long-standing lesions. Different patterns of dissociation may be
encountered due to interindividual particularities and cerebral plasticity. The
presented patient is unique by demonstrating new insight into expressive language
dissociation, emphasizing the role of a preoperative language fMRI panel and the
capability of intraoperative language mapping for identifying special language
networks.
PMID- 24357071
TI - Management of low-grade third ventricular ependymomas in adults by endoscopic
biopsy followed by gamma knife radiosurgery.
AB - BACKGROUND: Third ventricular ependymomas in adults are rare lesions for which
the optimal management strategy has not been determined. OBJECTIVES: We describe
our results using a strategy of endoscopic biopsy followed by gamma knife
radiosurgery in two patients with low-grade (World Health Organization [WHO]
grade II) third ventricular ependymomas. METHODS: A retrospective analysis of
clinical notes, operative records, and neuroimaging was performed for the two
patients in this study. The patients both presented with obstructive
hydrocephalus and had endoscopic third ventriculostomy performed along with
endoscopic tumor biopsy. In both patients the pathology revealed papillary
ependymoma WHO grade II. In one patient the endoscopic third ventriculostomy
failed, and ventriculoperitoneal shunt placement was necessary. Postoperatively,
gamma knife radiosurgery was performed at 1 and 4 months, respectively. RESULTS:
Both patients in the study experienced symptom resolution following treatment of
the hydrocephalus. They returned to their preoperative level of social and
occupational function. There was tumor enlargement in one patient in the interval
between the initial surgery and the gamma knife treatment. However, neither tumor
has enlarged since gamma knife treatment with follow-up of 35 and 41 months,
respectively. CONCLUSIONS: The strategy of endoscopic biopsy followed by gamma
knife radiosurgery for adult WHO grade II third ventricular ependymomas has
produced acceptable clinical results 3 years posttreatment. Stereotactic
radiosurgery without prior microsurgical resection has not previously been
reported in these tumors. Longer follow-up is required to evaluate the durability
of this treatment.
PMID- 24357072
TI - Can recurrence of chronic subdural hematoma be predicted?
PMID- 24357073
TI - Drugs, money, and power: the Canadian drug shortage.
AB - This article describes the shortage of generic injectable medications in Canada
that affected hospitals in 2012. It traces the events leading up to the drug
shortage, the causes of the shortage, and the responses by health administrators,
pharmacists, and ethicists. The article argues that generic drug shortages are an
ethical problem because health care organizations and governments have an
obligation to avoid exposing patients to resource scarcity. The article also
discusses some options governments could pursue in order to secure the drug
supply and thereby fulfill their ethical obligations.
PMID- 24357074
TI - Making sense of child welfare when regulating human reproductive technologies.
AB - Policy-makers have attempted to frame the ethical requirements that are relevant
to the creation of human beings via reproductive technologies. Various reports
and laws enacted in New Zealand, Canada, Australia, and Britain have introduced
tests for how we should weigh child welfare when using these technologies. A
number of bioethicists have argued that child welfare should be interpreted as a
"best interests" test. Others have argued that there are ethical reasons why we
should abandon this kind of test. I will argue that at least some of the relevant
policy can be interpreted as requiring those wishing to exercise their
procreative liberty to have a reasonable plan to care and nurture any resulting
child, thereby respecting the internal preconditions of that liberty. This
interpretation of child welfare requirements answers some of the ethical worries
about a child welfare test.
PMID- 24357075
TI - High-resolution anatomy of the human brain stem using 7-T MRI: improved detection
of inner structures and nerves?
AB - INTRODUCTION: The purpose of this paper is to assess the value of 7 Tesla (7 T)
MRI for the depiction of brain stem and cranial nerve (CN) anatomy. METHODS: Six
volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D
SPACE T2, T2, and PD images to establish scanning parameters targeted at
optimizing spatial resolution. Direct comparisons between 3 and 7 T were
performed in two additional subjects using the finalized sequences (3 T: T2, PD,
MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of
structures were evaluated by two neuroradiologists using a standardized score
sheet. RESULTS: Sequences could be established for high-resolution 7 T imaging
even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images
provided depiction of inner brain stem structures such as pons fibers, raphe,
reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE
provided clear depiction of the CNs. 3D T2 images improved depiction of inner
brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence
provided improved contrast to some inner structures, extended areas were
influenced by artifacts due to image disturbances from susceptibility
differences. CONCLUSIONS: Seven-tesla imaging of basal brain areas is feasible
and might have significant impact on detection and diagnosis in patients with
specific diseases, e.g., trigeminal pain related to affection of the nerve root.
Some inner brain stem structures can be depicted at 3 T, but certain sequences at
7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo
images of deep brain stem structures.
PMID- 24357076
TI - Refinement of the critical region of 1q41q42 microdeletion syndrome identifies
FBXO28 as a candidate causative gene for intellectual disability and seizures.
AB - A clinically recognizable syndrome associated with 1q41q42 microdeletion has
recently been described in the literature (OMIM 612530). Patients with
microdeletions in this region of chromosome 1 typically have developmental delay,
characteristic dysmorphic features, and a predisposition to seizures.
Malformations such as congenital diaphragmatic hernia and cleft lip have also
been described. There has been considerable interest in mapping the smallest
region of overlap for this syndrome in order to identify the critical pathogenic
genes. The smallest region of overlap has recently been refined to a region
encompassing four genes. Using array comparative genome hybridization (array
CGH), we have identified a female with a 590-kB deletion within
chromosome1q41q42. This patient's deletion further refines the previously defined
region of overlap to a single gene, FBXO28. We propose that FBXO28 is a possible
candidate causative gene contributing to the intellectual disability and seizure
phenotype observed in 1q41q42 microdeletion syndrome.
PMID- 24357077
TI - Simultaneous determination of imperatorin and its metabolites in vitro and in
vivo by a GC-MS method: application to a bioavailability and protein binding
ability study in rat plasma.
AB - In this study, a simple and sensitive gas chromatography-mass spectrometry method
was developed for the study of bioavailability and protein binding and the
metabolism of imperatorin in rat. The results showed that the pharmacokinetics of
imperatorin after intravenous and oral administration in rats exhibited linear
characteristics. The absolute bioavailability of imperatorin was calculated as
~3.85, ~33.51 and ~34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low
bioavailability of imperatorin may be attributed to the poor absorption or
extensive metabolism. The phase I metabolites of imperatorin formed in vitro by
rat liver microsomes were studied, and two metabolites were isolated and
identified as xanthotoxol and heraclenin. Following oral administration of
imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two
potential metabolites (xanthotoxol and heraclenin) were detected in rat urine.
However, none of potential metabolites was detected in rat feces and bile. The
results showed that the metabolites of imperatorin were excreted by kidney, and
heraclenin was associated with an active component. Demethylation and
oxygenization were the main metabolic pathways. In vitro plasma protein binding
of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0
and 50.0 ug/mL, respectively, indicating that imperatorin showed slow
distribution into the intra- and extracellular space.
PMID- 24357078
TI - BOLD MRI in the brain of fetal sheep at 3T during experimental hypoxia.
AB - PURPOSE: To calculate regional fetal brain oxygen saturation (sO2) during hypoxia
in sheep. MATERIALS AND METHODS: Eight pregnant ewes were examined at a 3T MR
scanner using blood oxygenation level-dependent magnetic resonance imaging (BOLD
MRI) to measure signal intensity changes of the fetal brain during a control
period and a period of induced hypoxia. Regions of interest were placed in the
fetal cerebrum to assess DeltaR2* from GRE signal intensity plateaus (S(control),
S(hypoxia)) and the relation between DeltaR2* and DeltapO2 was analyzed. A probe
was placed surgically in the fetal brain to directly measure local pO2 as a
reference standard. Baseline and hypoxic pO2 values were recorded and compared
(DeltapO2). RESULTS: Mean fetal brain pO2 decreased from 14.3 mmHg (95%
confidence interval [CI]: 10-19) to 3.4 mmHg (95% CI: 2-5) during hypoxia (mean
DeltapO2 = 10.9 mmHg and DeltaR2* = -5s(-1)). A significant correlation between
DeltaR2* and DeltapO2 was noted (r = 0.93, P < 0.001), and conversion of pO2 into
sO2 resulted in a linear regression coefficient of (-0.14 +/- 0.01)s(-1)/% (r(2)
= 0.91). CONCLUSION: Measured fetal brain BOLD-MRI was compared and converted to
pO2, followed by calculation of cerebral sO2.
PMID- 24357079
TI - Right atrial compression due to diaphragmatic eventration after liver
transplantation: successful treatment by diaphragmatic plication.
PMID- 24357080
TI - Location and architecture of an antibody-binding site of influenza A virus
nucleoprotein.
AB - Amino acid positions recognized by monoclonal antibodies (MAbs) in the influenza
A virus nucleoprotein (NP) have been reported. As these residues were scattered
in the three-dimensional (3D) structure of NP, no patterns of the architecture of
antibody-binding sites could be inferred. Here, we used site-specific mutagenesis
and ELISA to screen the amino acids surrounding position 470 recognized by the
MAb 3/1 as a linear epitope. Ten amino acid residues involved in the reaction of
NP with the MAb 3/1 and the MAb 469/6 were identified. Our data are the first to
outline a compact site recognized by MAbs in the 3D structure of the influenza
virus NP.
PMID- 24357081
TI - Adjuvant effect of CD40 on H5N1 DNA vaccine in mice.
AB - H5N1 viruses cause severe and often fatal disease in humans. DNA vaccines have
been shown to provide some protection in many animal models against H5N1
influenza virus infection, but this protection is not complete. To enhance the
immunogenicity of an H5N1 DNA vaccine, we constructed the eukaryotic expression
systems pcD-CD40 and pcD-HA. The expression of pcD-HA or pcD-CD40 in transfected
BHK cells was confirmed by reverse transcription polymerase chain reaction (RT
PCR). The constructs were then used to immunize BALB/c mice intramuscularly three
times at two-week intervals. The titers of serum HA-specific antibodies were
determined by ELISA, and the expression levels of the cytokines IL-2, IL-4, IL-6
and TNF-alpha were determined by real-time PCR. The results showed that CD40 as a
molecular adjuvant significantly enhanced the production of serum anti-HA
antibodies and increased the levels of the Th2 cytokines IL-4 and IL-6,
suggesting that co-immunization with CD40 upregulated the humoral immune
responses to the DNA vaccine in BALB/c mice. This study will provide important
information for the selection of adjuvants for DNA vaccines against HPAI H5N1
viruses or other subtypes of human influenza viruses.
PMID- 24357082
TI - Impact of a Web-based intervention on maternal caries transmission and prevention
knowledge, and oral health attitudes.
AB - Poor oral health knowledge is thought to significantly contribute to the
incidence of early childhood caries, the most common childhood disease in the
U.S. This study assessed the effectiveness of a web-based educational program in
increasing oral health and caries transmission knowledge, attitudes and planned
behavior among mothers and primary caregivers. Study participants were recruited
from subscribers to an online health information newsletter distributed by a
national dental insurance company and from visitors to a health information
website sponsored by the same company. Participants completed pre- and post
intervention surveys and viewed a brief educational program. Results were
analyzed for pre- to post-test changes in knowledge and attitudes. Planned
behavior change was also assessed. 459 participants completed pre-and post-test
surveys. The sample was typically more insured (91.3 %), and college educated
(76.9 %), than the general population. At baseline, respondents were
knowledgeable about caries and its prevention; however, their specific knowledge
about caries transmission was limited. There was a significant increase in caries
knowledge from baseline to follow-up, particularly regarding caries transmission.
At baseline less than half of the participants (48.8 %) knew that mothers/primary
caregivers play a large role in passing cavity causing germs to children and 43.1
% knew that there is a defined period of time when the risk of transmission of
cariogenic bacteria is greatest; however in post-testing 99.6 % and 98.3 %
answered these question correctly respectively (p < 0.001). Results indicate that
a web-delivered oral health intervention can increase dental knowledge and
increase participants' plans to prevent maternal caries transmission. The
provision of web-delivered education to primary caregivers can be an effective
and low cost strategy for promoting maternal and infant oral health.
PMID- 24357083
TI - Unhealthy weight control behaviors and related risk factors in Massachusetts
middle and high school students.
AB - Unhealthy weight control behaviors may be precursors to clinical eating
disorders; therefore, it is important to identify these actions, and what may
trigger them, as early as possible. We used 2009 and 2011 Massachusetts Youth
Health Survey data for middle and high school students. We studied age, sex, and
race disparities related to unhealthy weight control behaviors in conjunction
with other risk factors such as body mass index (BMI), body weight perception,
involvement in bullying, and depressive symptoms. The surveys were completed in
public schools. Bivariate and multinomial regression analyses were conducted to
assess associations between weight control behaviors and BMI categories, body
weight perception, bullying involvement, and depressive symptoms. Poor body
weight perception, bullying involvement, and depressive symptoms were associated
with significantly elevated odds of reporting unhealthy weight control behaviors
in both middle and high school students. Most patterns were consistent for middle
and high school students, with obesity and bullying involvement being prevailing
risks for high school students. Though females were more likely to report
unhealthy weight control behaviors we also showed the rarely presented prevalence
of male involvement in disordered eating behaviors including those who perceived
themselves to be underweight. Health education classes and school-based
interventions may be two strategies to help prevent the development of unhealthy
weight control behaviors. Continuation of youth surveys that gather data on
weight control behaviors and known risk factors is essential for observing
changes in behaviors over time.
PMID- 24357084
TI - The pharmacology of imepitoin: the first partial benzodiazepine receptor agonist
developed for the treatment of epilepsy.
AB - Although benzodiazepines (BZDs) offer a wide spectrum of antiepileptic activity
against diverse types of epileptic seizures, their use in the treatment of
epilepsy is limited because of adverse effects, loss of efficacy (tolerance), and
development of physical and psychological dependence. BZDs act as positive
allosteric modulators of the inhibitory neurotransmitter GABA by binding to the
BZD recognition site ("BZD receptor") of the GABAA receptor. Traditional BZDs
such as diazepam or clonazepam act as full agonists at this site, so that one
strategy to resolve the disadvantages of these compounds would be the development
of partial agonists with lower intrinsic efficacy at the BZD site of the GABAA
receptor. Several BZD site partial or subtype selective compounds, including
bretazenil, abecarnil, or alpidem, have been developed as anxioselective
anxiolytic drugs, but epilepsy was not a target indication for such compounds.
More recently, the imidazolone derivatives imepitoin (ELB138) and ELB139 were
shown to act as low-affinity partial agonists at the BZD site of the GABAA
receptor, and imepitoin was developed for the treatment of epilepsy. Imepitoin
displayed a broad spectrum of anticonvulsant activity in diverse seizure and
epilepsy models at tolerable doses, and, as expected from its mechanism of
action, lacked tolerance and abuse liability in rodent and primate models. The
more favorable pharmacokinetic profile of imepitoin in dogs versus humans led to
the decision to develop imepitoin for the treatment of canine epilepsy. Based on
randomized controlled trials that demonstrated antiepileptic efficacy and high
tolerability and safety in epileptic dogs, the drug was recently approved for
this indication in Europe. Hopefully, the favorable profile of imepitoin for the
treatment of epilepsy in dogs will reactivate the interest in partial BZD site
agonists as new treatments for human epilepsy.
PMID- 24357085
TI - A cell of origin gene signature indicates human bladder cancer has distinct
cellular progenitors.
AB - There are two distinct forms of urothelial (bladder) cancer: muscle-invasive (MI)
and nonmuscle invasive (NMI) disease. Since it is currently believed that bladder
cancer arises by transformation of urothelial cells of the basal layer, bladder
cancer stem cells (CSCs) have been isolated based on expression markers found in
such cells. However, these CSCs have only been identified in MI tumors raising
the intriguing hypothesis that NMI tumor progenitors do not arise from the basal
compartment. To test this hypothesis, we carried out genome-wide expression
profiling of laser capture microdissected basal and umbrella cells, the two most
histologically distinct cell types in normal urothelium and developed a cell of
origin (COO) gene signature that distinguishes these. The COO signature was a
better predictor of stage and survival than other bladder, generic, or breast CSC
signatures and bladder cell differentiation markers in multiple patient cohorts.
To assess whether NMI and MI tumors arise from a distinct progenitor cell (DPC)
or common progenitor cell, we developed a novel statistical framework that
predicts COO score as a function of known genetic alterations (TP53, HRAS, KDM6A,
and FGFR3) that drive either MI or NMI bladder cancer and compared this to the
observed COO score of the tumor. Analysis of 874 patients in five cohorts
established the DPC model as the best fit to the available data. This observation
supports distinct progenitor cells in NMI and MI tumors and provides a paradigm
shift in our understanding of bladder cancer biology that has significant
diagnostic and therapeutic implications.
PMID- 24357087
TI - Are all tissue donors recognised? A cohort study in three Dutch hospitals.
AB - Nowadays, the demand for tissue transplantation has significantly increased. To
optimize donor recruitment, the potential availability of tissue donors has to be
evaluated. In 2011 we conducted a cohort study in three Dutch hospitals in the
Netherlands. The potential amount of eligible tissue donors found, based on
medical records in these hospitals is compared to the physician's donation form
report. In total 1,342 patient records were analysed. From these records, the
donation officers considered 484 patients as a potential tissue donor (36.1 %).
Despite the absence of contra-indication, the physician did not recognise 25 % (n
= 123/484) of potential tissue donors. Physicians' lack of sufficient knowledge
of tissue donation was the main cause of adequately identifying tissue donors. A
higher percentage of tissue donors in these Dutch hospitals should be feasible
through creating awareness and education regarding tissue donation.
PMID- 24357086
TI - Management of pediatric subglottic cysts using the Bugbee fulgurating electrode.
AB - IMPORTANCE: Subglottic cysts are an important cause of pediatric airway
obstruction. We describe the typical presentation and management of subglottic
cysts, with historical recurrence rates between 12.5% and 71.0%, and treatment
using the Bugbee fulgurating diathermy electrode as a technique to successfully
manage subglottic cysts with a low recurrence rate. OBSERVATIONS: A retrospective
review was performed on 16 consecutive patients treated for subglottic cysts at a
single tertiary-care facility. The mean gestational age was 26.9 weeks, with a
male to female ratio of 4.3:1. All patients had at least 1 prior intubation, with
a mean of 1.8 prior intubations per patient. Biphasic stridor was the most common
presenting symptom, occurring at a mean of 7.3 months after the last extubation.
At the time of diagnosis, patients were found to have a mean of 1.6 cysts, and
the left lateral subglottic wall was the most common location of unilateral
cysts. Nine patients (56%) had an associated laryngeal pathologic condition.
Symptomatic cyst recurrence occurred in only 6% of patients, and no major
complications were reported. CONCLUSIONS AND RELEVANCE: This review presents a
treatment method for subglottic cysts that is safe and effective and has a
symptomatic recurrence rate lower than previously reported.
PMID- 24357089
TI - Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide
in Taiwanese subjects.
AB - To understand the genetic makeup and impact on pharmacokinetics (PK) in the
Taiwanese population, we analyzed the pharmacogenetic (PG) profile and
demonstrated its effects on enzyme metabolism using indapamide as an example. A
multiplex mass spectrometry method was used to examine the single nucleotide
polymorphism (SNP) profile of eight major phases I and II metabolic enzymes in
1,038 Taiwanese subjects. A PG/PK study was conducted in 24 healthy subjects to
investigate the possible effects of 28 SNPs on drug biotransformation. Among the
genetic profile analyzed, eight SNPs from CYP2A6, CYP2C19, CYP2D6, CYP2E1,
CYP3A5, and UGT2B7 showed higher variant frequencies than those previously
reported in Caucasians or Africans. For instance, we observed 14.7% frequency of
the SNP rs5031016 (I471T) from CYP2A6 in Taiwanese, whereas 0% variation was
reported in Caucasians and Africans. The PG/PK study of indapamide demonstrated
that the polymorphic SNPs CYP2C9 rs4918758 and CYP2C19 rs4244285 appeared to
confer lowered enzyme activity, as indicated by increased C max (25% ~ 64%),
increased area under the plasma level-time curves (30~76%), increased area under
the time infinity (43% ~ 80%), and lower apparent clearance values than PK for
wild-type indapamide. Our results reinforce the biochemical support of CYP2C19 in
indapamide metabolism and identify a possible new participating enzyme CYP2C9.
The PG/PK approach contributed toward understanding the genetic makeup of
different ethnic groups and associations of enzymes in drug metabolism. It could
be used to identify two genetic markers that enable to differentiate subjects
with varied PK outcomes of indapamide.
PMID- 24357090
TI - Bidirectional global spontaneous network activity precedes the canonical
unidirectional circuit organization in the developing hippocampus.
AB - Spontaneous network activity is believed to sculpt developing neural circuits.
Spontaneous giant depolarizing potentials (GDPs) were first identified with
single-cell recordings from rat CA3 pyramidal neurons, but here we identify and
characterize a large-scale spontaneous network activity we term global network
activation (GNA) in the developing mouse hippocampal slices, which is measured
macroscopically by fast voltage-sensitive dye imaging. The initiation and
propagation of GNA in the mouse is largely GABA-independent and dominated by
glutamatergic transmission via AMPA receptors. Despite the fact that signal
propagation in the adult hippocampus is strongly unidirectional through the
canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA
in the developing hippocampus originates in distal CA3 and propagates both
forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows
prominent backward propagation in the developing hippocampus from CA3 to DG.
Mouse GNA is strongly correlated to electrophysiological recordings of highly
localized single-cell and local field potential events. Photostimulation mapping
of neural circuitry demonstrates that the enhancement of local circuit
connections to excitatory pyramidal neurons occurs over the same time course as
GNA and reveals the underlying pathways accounting for GNA backward propagation
from CA3 to DG. The disappearance of GNA coincides with a transition to the adult
like unidirectional circuit organization at about 2 weeks of age. Taken together,
our findings strongly suggest a critical link between GNA activity and maturation
of functional circuit connections in the developing hippocampus.
PMID- 24357091
TI - Link between angiographic extent and severity of coronary artery disease and
degree of sensorineural hearing loss.
AB - AIMS: Atherosclerosis is a systemic disease that can affect the whole arterial
tree. An important cause of neuronal degeneration is atherosclerosis, which may
lead to sensorineural hearing loss. We aimed to investigate the relationship
between the angiographic severity and extent of coronary artery disease, which is
a surrogate of atherosclerotic burden, and the degree of sensorineural hearing
loss. PATIENTS AND METHODS: Out of 381 consecutive patients who underwent
coronary angiography for symptoms suggesting ischemic heart disease and who had
ischemia detected by a noninvasive stress test, 265 patients [mean age, 61.5 +/-
13.0 years; median age (25th-75th percentile), 59 years (50.5-67)], including 146
male (55.1 %) subjects met the eligibility criteria and were enrolled.
Audiological measurements (hearing levels and discrimination scores) were
performed before the coronary angiography. The Gensini score was calculated for
each angiogram. RESULTS: There was a statistically significant positive
correlation between the degree of hearing loss at all frequencies analyzed (250,
500, 1,000, 2,000, 4,000 Hz) and the Gensini score (p < 0.05 for all
frequencies), which remained significant after adjustment according to age and
other risk factors. A statistically significant negative correlation was observed
between the Gensini score and the speech discrimination score (p < 0.05).
CONCLUSION: The findings of this study suggest that the angiographic severity and
extent of coronary artery disease are significantly and independently correlated
with the degree of hearing loss. Sensorineural hearing loss was more prominent in
patients with higher Gensini scores. We propose that the findings of this study
warrant further research and should be verified in large-scale studies.
PMID- 24357092
TI - Predictive value of plasma asymmetric dimethylarginine, homocysteine, and high
sensitive CRP levels in occult coronary artery disease: A multidetector-row
computed tomography study.
AB - BACKGROUND: Multidetector-row computed tomography (MDCT) is an attractive
noninvasive imaging modality for detecting coronary atherosclerotic plaques,
which may be underestimated by conventional angiography. The aim of our study was
to determine the predictive value of plasma asymmetric dimethylarginine (ADMA),
homocysteine, and high-sensitivity C-reactive protein (hsCRP) levels for occult
coronary artery disease (CAD). PATIENTS AND METHODS: Thirty-five patients with
angiographically normal coronary arteries (NCA) were consecutively included in
our study. They underwent MDCT including indications and were divided into an NCA
group (18 subjects, 8 male, 46 +/- 8 years) and an occult CAD group (17 subjects,
11 male, 48 +/- 9 years), with respect to the presence of coronary plaque. Plasma
ADMA, homocysteine, and hsCRP levels were measured in blood samples. RESULTS:
Plasma ADMA and homocysteine levels of the occult CAD group were significantly
higher than those of the NCA group. A nonsignificant trend was observed for
higher serum hsCRP levels in the occult CAD group. Receiver operating
characteristics analysis revealed that an ADMA level of > 0.71 MUmol/l could
predict patients with occult CAD (sensitivity, 76 %; specificity, 67 %). The
discriminative power of ADMA in distinguishing the occult CAD group from the NCA
group was high (area under the curve, 0.80; CI, 0.66-0.95, p = 0.002), while it
was not sufficiently high for homocysteine and hsCRP (p > 0.05). CONCLUSION:
Plasma ADMA is a useful parameter for predicting subclinical atherosclerosis,
whereas homocysteine and hsCRP are not, and it may be complementary to the
conventional cardiovascular risk factors for the selection of individuals at high
risk for CAD before undertaking MDCT procedures in clinical practice.
PMID- 24357093
TI - Left ventricular hypertrabeculation/noncompaction as a cause of juvenile embolic
stroke.
PMID- 24357094
TI - Transesophageal echocardiographic evaluation of a giant intracardiac mass
originating from the left superior pulmonary vein: Transvenous metastasis of a
rare pulmonary carcinoma.
PMID- 24357095
TI - Surgical anatomy of round window and its implications for cochlear implantation.
AB - The objective of this work was to study the morphometry and morphology of the
round window (RW) and its relationships with the internal carotid artery, jugular
bulb (JB), facial nerve and oval window (OW). Fifty cadaveric temporal bones were
microdissected to expose the medial wall of the middle ear. The areas around the
RW were cleared and its shape, height and width were noted. Its distances from
the carotid canal (CC), jugular fossa (JF), facial canal (FC), and OW were
measured. Oval, round, triangular, comma, quadrangular, and pear shapes of RW
were observed. The average height and width of the RW were 1.62 +/- 0.77 mm and
1.15 +/- 0.39 mm, respectively. There was a statistically significant correlation
(r = 0.4, P < 0.01) between the height and width. The distances between the RW
and the CC, JF, FC, and OW were in the ranges 4.39-11.05 mm, 0.38-8.65 mm, 2.99
6.3 mm, and 1.39-3.57 mm, respectively. In 8% of cases, the distance between the
RW and the JF was <1 mm. There were no statistically significant differences with
regard to age group, gender, or side. Electrode insertion can be challenging in
cases where the height and width of the RW are <1 mm. The thin bone separating
the roof of the JF from the RW (<1 mm in 8%) highlights a potential risk of
injury to the JB during cochleostomy placement. This information could be useful
for selecting cochlear implant electrodes in order to avoid potential risks to
vital neurovascular structures during implant surgery.
PMID- 24357097
TI - Occurrence and removal of selected pharmaceuticals and personal care products in
three wastewater-treatment plants.
AB - Residues of pharmaceuticals and personal care products (PPCPs) have been detected
in surface waters. Incomplete removal of these compounds by wastewater-treatment
plants (WWTPs) results in their presence in effluents and finally in surface
waters. The occurrence and removal of four PPCPs was investigated in three WWTPs
in Mississippi, USA, during a period of 1 year. Influent and effluent were
sampled from the three WWTPs. Upstream and downstream samples of the WWTPs were
also collected. All four PPCPs were detected in all influents where
sulfamethoxazole showed the highest concentration levels with a median
concentration of 1,640 ng/L, and carbamazepine was detected at the lowest level
with a median concentration of 132 ng/L. Different PPCPs were removed to
different extents varying from 99 to 100 %. Gemfibrozil showed the highest
removal rates (73-100 %), whereas carbamazepine showed the lowest (-99 to -30 %).
Secondary activated sludge in oxidation-ditch process showed remarkable PPCP
specific removal rates. Galaxolide was removed more than the other PPCPs, and
sulfamethoxazole showed the least removal. Galaxolide was found to be a
predominant PPCP in effluent among the PPCPs studied, and it was detected in all
downstream (14.1-428.2 ng/L) and upstream (4.1-60.0 ng/L) samples.
Sulfamethoxazole was removed more during the summer than the winter season. A
clear increase of PPCP concentrations was observed in most downstream samples
compared with upstream samples suggesting that discharges from WWTPs are the
major source of PPCPs in surface waters.
PMID- 24357096
TI - Genetic susceptibility to lung cancer based on candidate genes in a sample from
the Mexican Mestizo population: a case-control study.
AB - BACKGROUND: Lung cancer (LC) is the leading cause of mortality caused by
neoplasias worldwide. Although cigarette smoking is the primary cause, not all
smokers develop LC. Polymorphic variations in genes associated with carcinogen
metabolism, DNA repair, and cell-cycle dysregulation may alter an individual risk
of developing LC. A polygenic cancer model was proposed, which considers genetic
susceptibility to cancer is a global mechanism and suggests that it might be
defined by the contributions of low-risk alleles in several candidate genes. This
study focused on the analysis of 15 polymorphisms in 12 low-penetrance genes in a
case-control study of a sample of Mexican Mestizo population. METHODS: A case
control study was performed with a total of 572 unrelated individuals, including
190 cases with a primary LC diagnosis and 382 healthy controls. The polymorphic
status of the individuals was determined by TaqMan probe and RFLP techniques. The
association between LC and genotype score (GS) was assessed by logistic
regression. RESULTS: The results suggests a protective effect of the genotypes
Arg/Lys of AhR rs2066853 (odds ratio [OR] 0.55, p = 0.03), Ile/Val of CYP1A1
rs1048943 (OR 0.49, p = 0.009), Tyr/His of EPHX1 rs1051740 (OR 0.53, p = 0.03),
and A/A of CCND1 rs603965 (OR 0.44, p = 0.02). Analyses using the GS suggest that
average cases have a larger number of risk alleles than controls (Student's t
test -4.85, p = 0.001; OR 1.25, p < 0.001). CONCLUSIONS: Our results suggest
significant differences between the GS for the cases and controls, which support
the hypothesis underlying the additive and polygenic models for lung cancer risk
depending on the polymorphisms in low-penetrance genes.
PMID- 24357099
TI - Functional anatomic dissociation of description and picture naming in the left
temporal lobe.
AB - Functional magnetic resonance imaging (fMRI) was used in a non-patient
experimental sample to assess the neuroanatomical dissociation of picture and
description naming (PN and DN) in temporal lobe (TL). The purpose was to
determine the generalizability of findings in semantic organization in the
epilepsy patient population to the broader population. It was hypothesized that,
akin to patient derived findings, DN would uniquely activate left TL regions
anterior to those associated with PN, while overlapping in middle and posterior
left TL. Participants (n = 16) underwent fMRI while silently naming target words
during a picture naming task (PNT; line drawings) and description naming task
(DNT; orthographic phrases). Analysis was a priori restricted to the left TL.
Group results of direct contrasts (DNT > PNT and PNT > DNT) confirmed the
hypothesized dissociation with DNT > PNT activating anterior left TL. Within
condition contrasts (DNT and PNT alone) yielded additional support, revealing
areas of shared and unique activation in each condition. This is the first
imaging study to contrast DN and PN in the same sample. The results suggest DN
and PN are meaningfully different constructs subserved by converging and
diverging TL neuroanatomy and may be differentially affected by disease.
PMID- 24357100
TI - The influence of ambient noise on maternal behavior in a Bornean sun bear
(Helarctos malayanus euryspilus).
AB - Anthropogenic noise has become a pervasive feature of both marine and terrestrial
habitats worldwide. While a comprehensive understanding of the biologically
significant impacts of noise on wildlife is lacking, concerns regarding its
influence persist. Noise is also a common feature in the zoological setting, and
much can be learned regarding the species-typical response to ambient noise by
studying animals in captivity. Here we correlate behavioral and vocal patterns in
a Bornean sun bear (Helarctos malayanus euryspilus) mother and cub with ambient
noise levels during the 6-month post-partum period. We hypothesized that loud
ambient noise would be correlated with changes in behavior, and predicted that
noise would be negatively correlated with maternal care behavior, potentially
masking cub vocalizations or providing a distraction to the mother. Contrary to
expectation, we found that the mother spent significantly more time attending to
her cub (P=0.03) on loud days. We also found that she tended to spend less time
feeding (P=0.08); however her time spent resting was not affected. The cub was
approximately twice as vocal on loud days, although these results were not
statistically significant (humming: P=0.10; squawks/cries: P=0.14). Taken
together, these results suggest that the behavioral response to ambient noise may
have potential energetic costs, and as a result efforts should be made to reduce
ambient noise exposure during the post-partum period.
PMID- 24357101
TI - A sensitive LC-MS/MS method for simultaneous determination of R-bambuterol and
its active metabolite R-terbutaline in human plasma and urine with application to
a clinical pharmacokinetic study.
AB - A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for
simultaneous determination of R-bambuterol and its active metabolite R
terbutaline in human plasma and urine was established. The inhibition for the
biotransformation of R-bambuterol in plasma was fully investigated. Plasma
samples were prepared on ice and neostigmine metilsulfate added as a
cholinesterase inhibitor immediately after sample collection. All samples were
extracted with ethyl acetate and separated on a C18 column under gradient elution
with a mobile phase consisting of methanol and water containing 5 mm ammonium
acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000
tandem mass spectrometer with positive electrospray ionization in multiple
reaction monitoring mode. The established method was highly sensitive with the
lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma.
In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R-bambuterol and R
terbutaline, respectively. The intra- and inter-day precisions were <12.7 and
<8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min
per sample made this method suitable for high-throughput determination. The
validated method has been successfully applied to the human pharmacokinetic study
of R-bambuterol involving 10 healthy volunteers.
PMID- 24357102
TI - Enhancing case ascertainment of Parkinson's disease using Medicare claims data in
a population-based cohort: the Cardiovascular Health Study.
AB - PURPOSE: We sought to improve a previous algorithm to ascertain Parkinson's
disease (PD) in the Cardiovascular Health Study by incorporating additional data
from Medicare outpatient claims. We compared our results to the previous
algorithm in terms of baseline prevalence and incidence of PD, as well as
associations with baseline smoking characteristics. METHODS: Our original case
ascertainment used self-reported diagnosis, antiparkinsonian medication, and
hospitalization discharge International Classification of Diseases-Ninth version
code. In this study, we incorporated additional data from fee-for-service
Medicare claims, extended follow-up time, review of hospitalization records, and
adjudicated cause of death. Two movement disorders specialists adjudicated final
PD status. We used logistic regression models and controlled for age, sex,
African American race, and education. RESULTS: We identified 75 additional cases
but reclassified 80 previously identified cases as not having PD. We observed
significant inverse association with smoking status (odds ratio = 0.42; 95%
confidence interval (CI) = 0.22, 0.79), and inverse linear trends with pack-years
(p = 0.005), and cigarettes per day (p = 0.019) with incident PD. All estimates
were stronger than those from the previous algorithm. CONCLUSIONS: Our enhanced
method did not alter prevalence and incidence estimates compared with our
previous algorithm. However, our enhanced method provided stronger estimates of
association, potentially due to reduced level of disease misclassification.
PMID- 24357103
TI - Heat shock protein 70 is required for optimal liver regeneration after partial
hepatectomy in mice.
AB - Liver regeneration is a complex process that restores functional tissue after
resection or injury, and it is accompanied by transient adenosine triphosphate
depletion and metabolic stress in hepatic parenchymal cells. Heat shock protein
70 (Hsp70) functions as a chaperone during periods of cellular stress and induces
the expression of several inflammatory cytokines identified as key players during
early liver regeneration. We, therefore, hypothesized that Hsp70 is required for
the initiation of regeneration. Investigations were carried out in a 70% partial
hepatectomy mouse model with mice lacking inducible Hsp70 (Hsp70(-/-)). Liver
regeneration was assessed postoperatively with the liver weight/body weight
(LW/BW) ratio, and sera and tissues were collected for analysis. In addition, the
expression of Hsp-related genes was assessed in a cohort of 23 human living donor
liver transplantation donors. In mice, the absence of Hsp70 was associated with a
reduced postoperative LW/BW ratio, Ki-67 staining, and tumor necrosis factor
alpha (TNF-alpha) expression in comparison with wild-type mice. TNF-alpha
expression was also reduced in livers from Hsp70(-/-) mice after induction with
lipopolysaccharide (1 mg/kg). Clinically, the transcription of multiple Hsp genes
(especially Hsp70 family members) was up-regulated after donor hepatectomy.
Together, these results suggest that the early phase of successful liver
regeneration requires the presence of Hsp70 to induce TNF-alpha. Further studies
are required to determine whether Hsp70 contributes to liver regeneration as a
chaperone by stabilizing specific interactions required for growth signaling or
as a paracrine inflammatory signal, as can occur in models of shock.
PMID- 24357104
TI - Frequency-specific hearing outcomes in pediatric type I tympanoplasty.
AB - IMPORTANCE: Middle ear disease is the primary cause of hearing loss in children
and has a significant impact on language development and academic performance.
Multiple prognostic factors have previously been examined, but there is little
published data regarding frequency-specific hearing outcomes. OBJECTIVE: To
examine the relationship between type I tympanoplasty in a pediatric population
and frequency-specific hearing changes, as well as the relationship between
several prognostic factors and graft retention. DESIGN, SETTING, AND
PARTICIPANTS: Retrospective medical chart review (February 2006 to October 2011)
of 492 consecutive pediatric otolaryngology patients undergoing type I
tympanoplasty for tympanic membrane (TM) perforation of any etiology at a
tertiary-care pediatric otolaryngology practice. INTERVENTIONS: Type I
tympanoplasty. MAIN OUTCOMES AND MEASURES: Preoperative and postoperative
audiometric data were collected for patients undergoing successful TM repair. It
was hypothesized before data collection that conductive hearing would improve at
all frequencies with no significant change in sensorineural hearing. Data
collected included air conduction at 250 to 8000 Hz, speech reception thresholds,
bone conduction at 500 to 4000 Hz, and air-bone gap at 500 to 4000 Hz.
Demographic data obtained included sex, age, size, mechanism, location of
perforation, and operative repair technique. RESULTS: Of 492 patients, 320 were
excluded; results were thus examined for 172 patients. Surgery was successful for
73.8% of patients. Perforation size was significantly associated with repair
success (mean [SD] surgical success rate of 38.6% [15.3%] vs surgical failure
rate of 31.4% [15.0%]; P < .01); however, mean (SD) age (9.02 [3.89] years
[surgical success] vs 8.52 [3.43] years [surgical failure]; P > .05) and repair
technique (medial [73.08%] vs lateral [76.47%] graft success; P > .99) were not.
Air conduction significantly improved from 250 to 2000 Hz (P < .001), did not
significantly improve at 4000 Hz (P = .08), and there was a nonsignificant
decline at 8000 Hz (P = .12). Speech reception threshold significantly improved
(20 vs 15 dB; P < .001). CONCLUSIONS AND RELEVANCE: This large review found an
association of TM perforation size with surgical success and an improvement in
speech reception threshold, air conduction at 250 to 2000 Hz, air-bone gap at 500
to 2000 Hz, and worsening bone conduction at 4000 Hz. Patients with high
frequency hearing loss due to TM perforation should not anticipate significant
recovery from type I tympanoplasty. Hearing loss at higher frequencies may
require postoperative hearing rehabilitation.
PMID- 24357105
TI - Urinary 3,3'-diindolylmethane: a biomarker of glucobrassicin exposure and indole
3-carbinol uptake in humans.
AB - BACKGROUND: Brassica vegetable consumption may confer a protective effect against
cancer, possibly attributable to their glucosinolates. Glucobrassicin is a
predominant glucosinolate and is the precursor of indole-3-carbinol (I3C), a
compound with anticancer effects. However, objective assessments of I3C uptake
from Brassica vegetables have not been successful. METHODS: We conducted a
randomized, crossover trial to test whether 3,3'-diindolylmethane (DIM, a
metabolite of I3C) excreted in the urine after consumption of raw Brassica
vegetables with divergent glucobrassicin concentrations is a marker of I3C uptake
from such foods. Twenty-five subjects were fed 50 g of either raw "Jade Cross"
Brussels sprouts (high glucobrassicin concentration) or "Blue Dynasty" cabbage
(low glucobrassicin concentration) once daily for 3 days. All urine was collected
for 24 hours after vegetable consumption each day. After a washout period,
subjects crossed over to the alternate vegetable. Urinary DIM was measured using
a novel liquid chromatography-electrospray ionization-tandem mass spectrometry
selected reaction monitoring (LC-ESI-MS/MS-SRM) method with [(2)H2]DIM as
internal standard. RESULTS: Urinary DIM was consistently and significantly higher
after Brussels sprouts feeding than after cabbage feeding, as evidenced by an
average difference of 8.73 pmol/mg creatinine (95% confidence interval, 5.36
12.10; P = 0.00002). CONCLUSION: We have successfully quantified urinary DIM
after uptake of I3C from food, and demonstrated that differences in
glucobrassicin exposure are reflected in urinary DIM levels. IMPACT: Our LC-ESI
MS/MS-SRM method and the results of our study indicate urinary DIM is a measure
of I3C uptake from Brassica vegetables, a finding that can be utilized in
prospective epidemiologic and chemoprevention studies.
PMID- 24357107
TI - Post-approval evaluation of effectiveness of risk minimisation: methods,
challenges and interpretation.
AB - Evaluation of the effectiveness of drug risk-minimisation measures is mandatory
for both risk evaluation and mitigation strategies (REMS) in the United States
and risk management plans in the European Union (EU-RMPs). Such evaluations aim
to assess the impact of risk-minimisation measures on the knowledge, attitudes or
behaviours of healthcare professionals or patients, the incidence of safety
concerns, and their impact on the overall benefit-risk balance. Although many
effectiveness evaluation models and methods are available, regulatory guidance
and policy are still evolving. This paper considers evaluation strategies,
challenges in evaluating risk minimisation post-authorisation, possible outcome
measures and their interpretation, and potential emerging regulatory policy
issues. Particular challenges include appropriate data collection, perceived and
real burdens of performing evaluation on clinical practice, lack of comparators
and benchmarking, and uncertainty about the best outcome measures.
PMID- 24357106
TI - Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer
risk.
AB - BACKGROUND: Imbalances in tryptophan metabolism have been linked to cancer
related immune escape and implicated in several cancers, including lung cancer.
METHODS: We conducted a nested case-control study within the European Prospective
Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung
cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six
of its metabolites were measured and evaluated in relation to lung cancer risk.
RESULTS: Tryptophan (Ptrend = 2 * 10(-5)) and the kynurenine/tryptophan ratio
(KTR; Ptrend = 4 * 10(-5)) were associated with lung cancer risk overall after
adjusting for established risk factors. The ORs comparing the fifth and first
quintiles (OR5th vs. 1st) were 0.52 [95% confidence interval (CI), 0.37-0.74] for
tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma
methionine (available from previous work, which was strongly correlated with
tryptophan), the associations of tryptophan (adjusted Ptrend = 0.13) and KTR
(Ptrend = 0.009) were substantially attenuated. KTR was positively associated
with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94,
Ptrend = 3 * 10(-5)) that was only marginally affected by adjusting for
methionine. CONCLUSIONS: This study indicates that biomarkers of tryptophan
metabolism are associated with subsequent lung cancer risk. Although this result
would seem consistent with the immune system having a role in lung cancer
development, the overall associations were dependent on methionine, and further
studies are warranted to further elucidate the importance of these metabolites in
lung cancer etiology. IMPACT: This is the first prospective study investigating
the tryptophan pathway in relation to lung cancer risk.
PMID- 24357108
TI - [Angiopoietin-2: prognostic parameter in cardiogenic shock].
PMID- 24357110
TI - Advances in metered dose inhaler technology: hardware development.
AB - Pressurized metered dose inhalers (MDIs) were first introduced in the 1950s and
they are currently widely prescribed as portable systems to treat pulmonary
conditions. MDIs consist of a formulation containing dissolved or suspended drug
and hardware needed to contain the formulation and enable efficient and
consistent dose delivery to the patient. The device hardware includes a canister
that is appropriately sized to contain sufficient formulation for the required
number of doses, a metering valve capable of delivering a consistent amount of
drug with each dose delivered, an actuator mouthpiece that atomizes the
formulation and serves as a conduit to deliver the aerosol to the patient, and
often an indicating mechanism that provides information to the patient on the
number of doses remaining. This review focuses on the current state-of-the-art of
MDI hardware and includes discussion of enhancements made to the device's core
subsystems. In addition, technologies that aid the correct use of MDIs will be
discussed. These include spacers, valved holding chambers, and breath-actuated
devices. Many of the improvements discussed in this article increase the ability
of MDI systems to meet regulatory specifications. Innovations that enhance the
functionality of MDIs continue to be balanced by the fact that a key advantage of
MDI systems is their low cost per dose. The expansion of the health care market
in developing countries and the increased focus on health care costs in many
developed countries will ensure that MDIs remain a cost-effective crucial
delivery system for treating pulmonary conditions for many years to come.
PMID- 24357109
TI - Antisocial behavior, psychopathic features and abnormalities in reward and
punishment processing in youth.
AB - A better understanding of what leads youth to initially engage in antisocial
behavior (ASB) and more importantly persist with such behaviors into adulthood
has significant implications for prevention and intervention efforts. A
considerable number of studies using behavioral and neuroimaging techniques have
investigated abnormalities in reward and punishment processing as potential
causal mechanisms underlying ASB. However, this literature has yet to be
critically evaluated, and there are no comprehensive reviews that systematically
examine and synthesize these findings. The goal of the present review is twofold.
The first aim is to examine the extent to which youth with ASB are characterized
by abnormalities in (1) reward processing; (2) punishment processing; or (3) both
reward and punishment processing. The second aim is to evaluate whether aberrant
reward and/or punishment processing is specific to or most pronounced in a
subgroup of antisocial youth with psychopathic features. Studies utilizing
behavioral methods are first reviewed, followed by studies using functional
magnetic resonance imaging. An integration of theory and research across multiple
levels of analysis is presented in order to provide a more comprehensive
understanding of reward and punishment processing in antisocial youth. Findings
are discussed in terms of developmental and contextual considerations, proposed
future directions and implications for intervention.
PMID- 24357111
TI - A prospective analysis of co-processed non-ionic surfactants in enhancing
permeability of a model hydrophilic drug.
AB - Paracellular route is a natural pathway for the transport of many hydrophilic
drugs and macromolecules. The purpose of this study was to prospectively evaluate
the ability of novel co-processed non-ionic surfactants to enhance the
paracellular permeability of a model hydrophilic drug metformin using Caco-2
(human colonic adenocarcinoma) cell model. A three-tier screen was undertaken to
evaluate the co-processed blends based on cytotoxicity, cellular integrity, and
permeability coefficient. The relative contribution of the paracellular and the
transcellular route in overall transport of metformin by co-processed blends was
determined. Immunocytochemistry was conducted to determine the distribution of
tight-junction protein claudin-1 after incubation with the co-processed blends.
It was found that novel blends of Labrasol and Transcutol-P enhanced metformin
permeability by approximately twofold with transient reduction in the
transepithelia electrical resistance (TEER) and minimal cytotoxicity compared
with the control, with the paracellular pathway as the major route of metformin
transport. Maximum permeability of metformin (~10-fold) was mediated by Tween-20
blends along with >75% reduction in the TEER which was irreversible over 24-h
period. A shift in metformin transport from the paracellular to the transcellular
route was observed with some Tween-20 blends. Immunocytochemical analysis
revealed rearrangement of the cellular borders and fragmentation on treatment
with Tween-20 blends. In conclusion, cytotoxicity, cellular integrity, and
permeability of the hydrophilic drugs can be greatly influenced by the
polyoxyethylene residues and medium chain fatty acids in the non-ionic
surfactants at clinically relevant concentrations and therefore should be
thoroughly investigated prior to their inclusion in formulations.
PMID- 24357114
TI - Interaction of methionine-enkephalins with raft-forming lipids: monolayers and
BAM experiments.
AB - Enkephalins (Tyr-Gly-Gly-Phe-Met/Leu) are opioid peptides with proven
antinociceptive action in organism. They interact with opioid receptors belonging
to G-protein coupled receptor superfamily. It is known that these receptors are
located preferably in membrane rafts composed mainly of sphingomyelin (Sm),
cholesterol (Cho), and phosphatidylcholine. In the present work, using Langmuir's
monolayer technique in combination with Wilhelmy's method for measuring the
surface pressure, the interaction of synthetic methionine-enkephalin and its
amidated derivative with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC),
Sm, and Cho, as well as with their double and triple mixtures, was studied. From
the pressure/area isotherms measured, the compressional moduli of the lipids and
lipid-peptide monolayers were determined. Our results showed that the addition of
the synthetic enkephalins to the monolayers studied led to change in the lipid
monolayers characteristics, which was more evident in enkephalinamide case. In
addition, using Brewster angle microscopy (BAM), the surface morphology of the
lipid monolayers, before and after the injection of both enkephalins, was
determined. The BAM images showed an increase in surface density of the mixed
surface lipids/enkephalins films, especially with double and triple component
lipid mixtures. This effect was more pronounced for the enkephalinamide as well.
These observations showed that there was an interaction between the peptides and
the raft-forming lipids, which was stronger for the amidated peptide, suggesting
a difference in folding of both enkephalins. Our research demonstrates the
potential of lipid monolayers for elegant and simple membrane models to study
lipid-peptide interactions at the plane of biomembranes.
PMID- 24357115
TI - Influence of MLS laser radiation on erythrocyte membrane fluidity and secondary
structure of human serum albumin.
AB - The biostimulating activity of low level laser radiation of various wavelengths
and energy doses is widely documented in the literature, but the mechanisms of
the intracellular reactions involved are not precisely known. The aim of this
paper is to evaluate the influence of low level laser radiation from an multiwave
locked system (MLS) of two wavelengths (wavelength = 808 nm in continuous
emission and 905 nm in pulsed emission) on the human erythrocyte membrane and on
the secondary structure of human serum albumin (HSA). Human erythrocytes
membranes and HSA were irradiated with laser light of low intensity with surface
energy density ranging from 0.46 to 4.9 J cm(-2) and surface energy power density
195 mW cm(-2) (1,000 Hz) and 230 mW cm(-2) (2,000 Hz). Structural and functional
changes in the erythrocyte membrane were characterized by its fluidity, while
changes in the protein were monitored by its secondary structure. Dose-dependent
changes in erythrocyte membrane fluidity were induced by near-infrared laser
radiation. Slight changes in the secondary structure of HSA were also noted. MLS
laser radiation influences the structure and function of the human erythrocyte
membrane resulting in a change in fluidity.
PMID- 24357116
TI - Neurotensin receptor1 antagonist SR48692 reduces proliferation by inducing
apoptosis and cell cycle arrest in melanoma cells.
AB - Malignant melanoma is highly aggressive, and always resistant to conventional
chemo-radiotherapy, which results in poor prognosis. As a specific antagonist of
neurotensin receptor 1 (NTSR1), emerging evidences confirmed that SR48692 can
reverse the pro-growth effect of neurotensin (NTS) by interrupting the
interaction between NTS and NTSR1. A375 melanoma cell line was used in this
experiment, and SR48692 was employed as the inhibitor of NTS/NTSR1 pathway. We
detected the expression of NTSR1 by NTSR1 immunofluorescence and Western blot.
After SR48692 treatment, cell proliferation was determined by cell counting, MTT
assay and BrdU incorporation study, the cell cycle and apoptosis were performed
by flow cytometry. At last Soft Agar Clonogenic assay and xenograft cancer mice
model in vivo were used to confirm our result. In this study, we showed that
NTSR1 is commonly high expressed in melanoma cells, but low expressed in normal
immortalized human keratinocyte line HaCaT. SR48692 not only reduced cell
proliferation and self-renewal potential in vitro, but also inhibited the tumor
growth derived from A375 cells in NOD/SCID mice in vivo. Further, we originally
reported that SR48692 inhibited cell proliferation through cell cycle arrest and
apoptosis. Considering the favorable toxicity profile in vitro and in vivo though
targeting NTS/NTSR1, SR48692 is worthy of further study and exploitation in
melanoma treatment.
PMID- 24357118
TI - Megakaryocytes contribute to the bone marrow-matrix environment by expressing
fibronectin, type IV collagen, and laminin.
AB - Megakaryocytes associate with the bone marrow vasculature where they convert
their cytoplasm into proplatelets that protrude through the vascular endothelium
into the lumen and release platelets. The extracellular matrix (ECM)
microenvironment plays a critical role in regulating these processes. In this
work we demonstrate that, among bone marrow ECM components, fibronectin, type IV
collagen, and laminin are the most abundant around bone marrow sinusoids and
constitute a pericellular matrix surrounding megakaryocytes. Most importantly, we
report, for the first time, that megakaryocytes express components of the
basement membrane and that these molecules contribute to the regulation of
megakaryocyte development and bone marrow ECM homeostasis both in vitro and in
vivo. In vitro, fibronectin induced a threefold increase in the proliferation
rate of mouse hematopoietic stem cells leading to higher megakaryocyte output
with respect to cells treated only with thrombopoietin or other matrices.
However, megakaryocyte ploidy level in fibronectin-treated cultures was
significantly reduced. Stimulation with type IV collagen resulted in a 1.4-fold
increase in megakaryocyte output, while all tested matrices supported proplatelet
formation to a similar extent in megakaryocytes derived from fetal liver
progenitor cells. In vivo, megakaryocyte expression of fibronectin and basement
membrane components was upregulated during bone marrow reconstitution upon 5
fluorouracil induced myelosuppression, while only type IV collagen resulted
upregulated upon induced thrombocytopenia. In conclusion, this work demonstrates
that ECM components impact megakaryocyte behavior differently during their
differentiation and highlights a new role for megakaryocyte as ECM-producing
cells for the establishment of cell niches during bone marrow regeneration.
PMID- 24357117
TI - The potential of Cystatin C and small dense LDL as biomarkers of coronary artery
disease risk in a young Indian population.
AB - Coronary artery disease (CAD) affects Indians 5-6 years earlier than in the west,
is diffuse and malignant, and poses a heavy burden on India's developing economy.
Traditional risk factors have failed to explain this high incidence of premature
CAD and hence this study investigated the association of two novel risk
biomarkers, cystatin C and small dense LDL (sdLDL) with the presence and severity
of CAD. Cystatin C and sdLDL were estimated in 204 CAD patients <=45 years of age
and compared with 161 age-matched healthy controls. The traditional lipid profile
parameters, i.e., cholesterol, LDL, HDL, triglycerides, apolipoproteins A1 and B,
and Lp(a) were also measured in both groups. Cystatin C was significantly raised
and mean LDL particle size significantly reduced in CAD patients as compared to
controls. 62.7 % of CAD patients showed pattern B while 37.3 % patients showed
pattern A. Of the traditional lipid tests, only HDL and apolipoprotein A1 showed
a significant decrease in the CAD group. sdLDL was significantly associated with
the severity of CAD, while cystatin C was not. Both cystatin C and sdLDL emerged
as independent risk factors, however, of the two, sdLDL was a more sensitive
predictor of CAD events. Cystatin C and mean LDL particle size are significantly
and independently associated with the presence of CAD events in patients <=45
years with normal kidney function. Hence, these novel risk biomarkers can be
useful tools in reducing the morbidity and mortality associated with CAD in the
productive Indian workforce.
PMID- 24357119
TI - Influences on anatomical knowledge: The complete arguments.
AB - Eight factors are claimed to have a negative influence on anatomical knowledge of
medical students: (1) teaching by nonmedically qualified teachers, (2) the
absence of a core anatomy curriculum, (3) decreased use of dissection as a
teaching tool, (4) lack of teaching anatomy in context, (5) integrated curricula
(problem-based learning or systems-based curricula), (6) inadequate assessment of
anatomical knowledge, (7) decreased anatomy teaching time, and (8) neglect of
vertical integration of anatomy teaching. A recent review revealed a lack of
evidence underpinning any of the claims owing to the poor quality of papers, and
recommendations were made for education and research on teaching in context and
the implementation of vertical integration and of assessment strategies. In this
article, we will describe the alleged factors fully, revealing additional
recommendations for improving anatomy education by promoting recognition for
teaching in institutions, by enhancing the professional recognition of anatomists
through the implementation of a national postgraduate training program, and by
encouraging anatomists to participate in educational research.
PMID- 24357120
TI - Integrated Laplacian-based phase unwrapping and background phase removal for
quantitative susceptibility mapping.
AB - Quantitative susceptibility mapping (QSM) is a recently developed MRI technique
that provides a quantitative measure of tissue magnetic susceptibility. To
compute tissue magnetic susceptibilities based on gradient echoes, QSM requires
reliable unwrapping of the measured phase images and removal of contributions
caused by background susceptibilities. Typically, the two steps are performed
separately. Here, we present a method that simultaneously performs phase
unwrapping and HARmonic (background) PhasE REmovaL using the LAplacian operator
(HARPERELLA). Both numerical simulations and in vivo human brain images show that
HARPERELLA effectively removes both phase wraps and background phase, whilst
preserving all low spatial frequency components originating from brain tissues.
When compared with other QSM phase preprocessing techniques, such as path-based
phase unwrapping followed by background phase removal, HARPERELLA preserves the
tissue phase signal in gray matter, white matter and cerebrospinal fluid with
excellent robustness, providing a convenient and accurate solution for QSM. The
proposed algorithm is provided, together with QSM and susceptibility tensor
imaging (STI) tools, in a shared software package named 'STI Suite'.
PMID- 24357121
TI - Patients' journeys through total joint replacement: patterns of medication use.
AB - OBJECTIVE: Medication is used to manage pain that results from both
osteoarthritis and total joint replacement (TJR). Research has provided insight
into how people living with osteoarthritis use pain relief medication. However,
it is not known whether elective TJR affects existing attitudes and behaviours
with regard to pain medications. Using qualitative methods, the present study
explored patterns of pain relief use around the time of TJR. METHOD: In-depth
face-to-face qualitative interviews were carried out with 24 patients two to four
weeks after they had undergone TJR for hip or knee osteoarthritis. Participants
were asked to reflect on their use of pain medication pre-surgery, while in
hospital and while recovering from their operation at home. Transcripts of the
audio-recorded interviews were imported into Atlas.ti(r) and thematic analysis
was used. RESULTS: Attitudes to pain relief medication and their use are not
static. Many participants change their use of pain medication around the time of
surgery. This shift was influenced by interactions with health professionals and
changing views on the acceptability, necessity and value of pain relief in
helping to manage an altered pain experience. DISCUSSION: Understanding reasons
for medication-taking behaviour during the journey through joint replacement may
be helpful to health professionals. Health professionals have a fundamental role
to play in challenging or reinforcing different treatment beliefs, which is the
basis for effective use of pain relief over the pre- to postoperative period.
PMID- 24357122
TI - An advanced and novel one-pot synthetic method for diverse benzo[c]chromen-6-ones
by transition-metal free mild base-promoted domino reactions of substituted 2
hydroxychalcones with beta-ketoesters and its application to polysubstituted
terphenyls.
AB - Novel and efficient one-pot syntheses of a variety of benzo[c]chromen-6-one
derivatives were accomplished using Cs2CO3-promoted reactions between substituted
2-hydroxychalcones and beta-ketoesters. These reactions involved domino Michael
addition/intramolecular aldol/oxidative aromatization/lactonization and provided
a rapid synthetic route for the production of biologically interesting novel
benzo[c]chromen-6-one molecules bearing several different substituents on benzene
rings. As an application of this methodology, several synthesized benzo[c]chromen
6-ones were transformed into highly functionalized novel terphenyls.
PMID- 24357123
TI - Using the dGEMRIC technique to evaluate cartilage health in the presence of
surgical hardware at 3T: comparison of inversion recovery and saturation recovery
approaches.
AB - OBJECTIVE: To evaluate the effect of metal artifact reduction techniques on
dGEMRIC T(1) calculation with surgical hardware present. MATERIALS AND METHODS:
We examined the effect of stainless-steel and titanium hardware on dGEMRIC T(1)
maps. We tested two strategies to reduce metal artifact in dGEMRIC: (1)
saturation recovery (SR) instead of inversion recovery (IR) and (2) applying the
metal artifact reduction sequence (MARS), in a gadolinium-doped agarose gel
phantom and in vivo with titanium hardware. T(1) maps were obtained using custom
curve-fitting software and phantom ROIs were defined to compare conditions
(metal, MARS, IR, SR). RESULTS: A large area of artifact appeared in phantom IR
images with metal when T(I) <= 700 ms. IR maps with metal had additional artifact
both in vivo and in the phantom (shifted null points, increased mean T(1) (+151 %
IR ROI(artifact)) and decreased mean inversion efficiency (f; 0.45 ROI(artifact),
versus 2 for perfect inversion)) compared to the SR maps (ROI(artifact): +13 %
T(1) SR, 0.95 versus 1 for perfect excitation), however, SR produced noisier T(1)
maps than IR (phantom SNR: 118 SR, 212 IR). MARS subtly reduced the extent of
artifact in the phantom (IR and SR). CONCLUSIONS: dGEMRIC measurement in the
presence of surgical hardware at 3T is possible with appropriately applied
strategies. Measurements may work best in the presence of titanium and are
severely limited with stainless steel. For regions near hardware where IR
produces large artifacts making dGEMRIC analysis impossible, SR-MARS may allow
dGEMRIC measurements. The position and size of the IR artifact is variable, and
must be assessed for each implant/imaging set-up.
PMID- 24357124
TI - Subchondral insufficiency fracture of the femoral head in a patient with
alkaptonuria.
AB - We report a patient with alkaptonuria accompanied by bilateral rapidly
destructive arthrosis of the hip. The destruction of the left hip joint with its
severe functional impairment necessitated total hip arthroplasty (THA). The
outcome was satisfactory. Both magnetic resonance imaging (MRI) and pathologic
findings were compatible with a subchondral insufficiency fracture. A year and
half later, during a follow-up visit, the patient complained of right coxalgia.
Radiography showed that the right femoral head had already disappeared, requiring
THA of the right hip. Although there have been a few reports of rapid destructive
hip osteoarthritis associated with ochronotic arthropathy, the pathogenesis of
the destructive change is not clear. Subchondral insufficiency fracture was
diagnosed on MR imaging and pathologically confirmed in our patient with
alkaptonuria, suggesting that subchondral insufficiency fracture is one of the
causes of ochronotic hip destruction.
PMID- 24357125
TI - Deletions in 14q24.1q24.3 are associated with congenital heart defects,
brachydactyly, and mild intellectual disability.
AB - Interstitial deletions of chromosome band 14q24.1q24.3 are apparently very rare.
We report on three unrelated patients with overlapping de novo deletions of sizes
5.4, 2.8, and 2.3 Mb in this region. While some clinical problems such as
intestinal malrotation, cryptorchidism, and ectopic kidney were only observed in
single patients, all three patients had mild intellectual disability, congenital
heart defects (truncus arteriosus, pulmonary atresia, atrial septal defect,
and/or ventricular septal defect), brachydactyly, hypertelorism, broad nasal
bridge, and thin upper lips. Likely haploinsufficiency of one or several of the
19 genes in the common deleted interval (ACTN1, DCAF5, EXD2, GALNTL1, ERH,
SLC39A9, PLEKHD1, CCDC177, KIAA0247, LOC100289511, SRSF5, SLC10A1, SMOC1, SLC8A3,
ADAM21P1, COX16, SYNJ2BP, SYNJ2BP-COX16, ADAM21) was responsible for these
manifestations, but apart from SMOC1, mutations in which cause autosomal
recessive Waardenburg anophthalmia syndrome, and ACTN1, mutations in which are
associated with congenital macrothrombocytopenia, no disease associations have so
far been reported for the other genes. Functional studies and a systematic search
for mutations or chromosome aberrations in this region will elucidate the role of
individual genes in the clinical manifestations and will provide insight into the
underlying biological mechanisms.
PMID- 24357126
TI - Enhanced recovery after bariatric surgery (ERABS): clinical outcomes from a
tertiary referral bariatric centre.
AB - There is paucity of data on Enhanced Recovery After Bariatric Surgery (ERABS)
protocols. This feasibility study reports outcomes of this protocol utilized
within a tertiary-referral bariatric centre. Data on consecutive primary
procedures (laparoscopic gastric bypasses, sleeve gastrectomies and gastric
bands) performed over 9 months within an ERABS protocol were prospectively
recorded. Interventions utilized included shortened preoperative fasts, intra
operative humidification, early mobilization and feeding, avoidance of fluid
overload, incentive spirometry, use of prokinetics and laxatives. Data collected
included demographics, co-morbidities, morbidity, mortality, length of stay (LOS)
and re-admissions. A total of 226 procedures (age [mean +/- SD], 45 +/- 11 years,
median [interquartile range] BMI 44.9 [41.0-49.0] kg/m2) were undertaken: 150
(66%) bypasses, 47 (21%) sleeves and 29 (13%) bands. Hypertension, diabetes
mellitus, sleep apnea and limited mobility were present in 40%, 34%, 24% and 9%
of patients, respectively. No anastomotic or staple line leaks/bleeds were
encountered. Ten (4.4%) patients developed postoperative morbidity (mainly
respiratory complications). One death occurred from massive pulmonary embolus in
a high-risk patient (despite insertion of preoperative-IVC filter). Respective
mean +/- SD LOS for bypasses, sleeves and bands were 1.88 +/- 1.12, 2.30 +/- 1.69
and 0.69 +/- 0.81 days. Successful discharge on the first postoperative day was
achieved in 37% and 28% of bypasses and sleeves, respectively. Day-case gastric
bands were performed in 48%. Thirty-day hospital re-admission occurred in six
(2.7%) patients. Applying an ERABS protocol was feasible, safe, associated with
low morbidity, acceptable LOS and low 30-day re-admission rates. The presence of
multiple medical co-morbidities should not preclude use of an ERABS protocol
within bariatric patients.
PMID- 24357127
TI - Six months of treatment with the endoscopic duodenal-jejunal bypass liner does
not lead to decreased systemic inflammation in obese patients with type 2
diabetes.
AB - Obesity is associated with chronic low-grade systemic inflammation. Bariatric
surgery has been shown to reduce this inflammation. Here, the effect of a
nonsurgical bariatric technique, the duodenal-jejunal bypass liner (DJBL), on
systemic inflammation was investigated. Seventeen obese patients with type 2
diabetes were treated with the DJBL for 6 months. Plasma C-reactive protein
(CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor
alpha (TNF-alpha) were determined prior to and during DJBL treatment. Three
months after initiation of DJBL treatment, TNF-alpha levels had increased from
1.8 +/- 0.1 to 2.1 +/- 0.1 pg/mL, whereas IL-6 increased from 2.7 +/- 0.3 to 4.0
+/- 0.5 pg/mL (both p < 0.05). CRP and MPO also increased, though the differences
were not significant. After 6 months, the levels of all parameters were similar
to baseline levels (CRP, 4.2 +/- 0.6 mg/L; TNF-alpha, 2.0 +/- 0.1 pg/mL; IL-6,
3.5 +/- 0.5 pg/mL; MPO, 53.6 +/- ng/mL; all p = ns compared to baseline). In the
current study, 6 months of endoscopic DJBL treatment did not lead to decreased
systemic inflammation.
PMID- 24357128
TI - The impact of preoperative weight loss before laparoscopic gastric bypass.
AB - BACKGROUND: The impact of preoperative weight loss on outcomes following
laparoscopic Roux-en-Y gastric bypass (LRYGB) is a controversial issue. We
evaluated our outcomes of LRYGB in patients who lost different amount of weight
prior to surgery. METHODS: Patients who underwent primary LRYGB were divided in
three groups on the basis of preoperative weight loss percentage. Group A
comprised 166 patients, who lost <5% of their weight preoperatively; group B
comprised 239 patients who lost >5 to 10% and group C included 143 patients who
lost >10%. Intra- and postoperative complications at 30 days, hospital stay, and
outcomes were evaluated. RESULTS: Significant difference was found in operative
(mean +/- SD) time [104.43 +/- 36.40 min in group A, 80.08 +/- 23.07 min in group
B, and 76.99 +/- 23.23 min in group C; p < 0.001 in group A versus group B or
group C; p = 0.210 in group B versus group C]. Difference in hospital stay was
significant (3.33 +/- 3.22 days in group A, 2.10 +/- 2.77 in group B, and 1.87 +/
1.44 in group C; p < 0.001 in group A versus groups B or C). Overall
postoperative morbidity rate was 33.13% in group A, 19.25% in group B, and 11.89%
in group C, with significant difference in group A versus groups B or C (p =
0.002 and p < 0.001). Mean excess weight loss was significantly higher (72.7%) in
group C versus group A (63.1%) (p = 0.015) at 12 months. CONCLUSIONS: Weight loss
>5% prior to LRYGB may reduce morbidity, and preoperative weight loss >10% may
improve weight loss outcomes at 1-year follow-up.
PMID- 24357129
TI - Selective expression of CSPG receptors PTPsigma and LAR in poorly regenerating
reticulospinal neurons of lamprey.
AB - Disability following spinal cord injury is due to failure of axon regeneration,
which has been ascribed to environmental factors in the central nervous system
and a developmental loss of intrinsic growth capacity in neurons. Recently, the
receptor-like protein tyrosine phosphatases, protein tyrosine phosphatase sigma
(PTPsigma) and leukocyte common antigen-related phosphatase (LAR), have been
identified as specific receptors for the regeneration-inhibiting matrix molecules
chondroitin sulfate proteoglycans (CSPGs). After spinal cord transection in
lampreys, axons of the large, identified reticulospinal neurons have
heterogeneous regenerative abilities. The bad-regenerating neurons also undergo a
delayed form of axotomy-induced apoptosis. In the present study, a lamprey
genomic database was used to identify homologs of CSPGs, clone PTPsigma and LAR,
and examine their mRNA expression. CSPG immunoreactivity was increased
significantly near the lesion at 2 weeks post transection, and decreased
thereafter. Both receptors were expressed selectively in the bad-regenerating
neurons and had overlapping cellular distributions. PTPsigma was upregulated with
age (LAR was not evaluated). By 2 weeks post transection, neurons expressing
PTPsigma also showed caspase activation, suggesting apoptosis. The probability of
axon regeneration for individual identified neurons was negatively correlated
with the expression level of PTPsigma in both control and spinal cord-transected
lampreys. In an animal 7 weeks post transection, regenerated axons were labeled
retrogradely from beyond the transection. PTPsigma expression and caspase
labeling was seen only in neurons whose axon had not regenerated. These results
are consistent with a possible role for PTPsigma (and LAR) in both retrograde
neuronal death and the poor intrinsic regenerative ability of bad-regenerating
neurons.
PMID- 24357131
TI - Prospecting in Huckel-space: from hinokitiol to non-benzenoid organic
electronics.
PMID- 24357132
TI - Factors influencing report of common mental health problems among psychologically
distressed adults.
AB - This study investigates the sociodemographic factors associated with self-report
of common mental problems by the psychologically distressed in order to gain
insight into the profile of the population subgroups least likely to receive
mental health support whenever needed. Data from the 2006-2008 french National
Survey on Health, Health Care and Insurance, were used, measuring psychological
distress based on the Mental Health Inventory MHI-5. The patterns associated with
education, employment situation and living arrangement were investigated in a
sample of 11,543 subjects aged 30-54 years. Men with lower educational level were
found to be doubly disadvantaged, as they were more subjected to distress than
those with higher educational level and at the same time less likely to report
common mental problems whenever distressed. While in both genders subjects not
living with a spouse and non-employed subjects were also more subjected to
distress, they were more likely than the others to report common mental problems
in presence of distress. The findings were discussed in terms of living
conditions, stigma, mental health literacy and help-seeking behaviour. Mental
health promotion programmes should aim at educating the public, and particularly
men and the lower educated public, on the signs of distress and their
significance.
PMID- 24357133
TI - Medication for Alzheimer's disease and associated fall hazard: a retrospective
cohort study from the Alzheimer's Disease Neuroimaging Initiative.
AB - BACKGROUND: Falls are common in the elderly, especially in those with cognitive
impairment. The elderly are often treated with several medications, which may
have both beneficial and deleterious effects. The use and type of medication in
Alzheimer's disease (AD) patients and association with falls is limited.
OBJECTIVE: We examined the association between falls and medication use in the
Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Diagnosis,
demographics, medication use, apolipoprotein E4 allele status and functional
activity level at baseline were gathered for 810 participants enrolled in the
ADNI, including healthy controls and subjects with mild cognitive impairment or
Alzheimer's. Reports detailing adverse event falls were tabulated. Baseline
characteristics were compared between subjects with and without one or more
falls. Cox proportional hazards models were conducted to evaluate the association
between subject characteristics and hazard of the first fall. RESULTS: Age (p <
0.0001), Functional Activities Questionnaire (p = 0.035), Beers List (p = 0.0477)
and medications for treating cognitive symptoms of Alzheimer's (p = 0.0019) were
associated with hazard of fall in the univariate model. In the final multivariate
model, after adjusting for covariates, Alzheimer's medication use (p = 0.0005)
was associated with hazard of fall. Medication was changed by the clinician after
an adverse fall event in 9% of the falls. About 7% of the falls were reported as
serious adverse events and 6% were reported to be severe. CONCLUSION: We found a
significant association between the use of symptomatic medication treating
cognitive symptoms in AD and hazard of fall after adjusting for age and Beers
List medication use. Additional pharmacovigilance of the association between
falls and Alzheimer's medication use is warranted.
PMID- 24357134
TI - Managing therapeutic competition in patients with heart failure, lower urinary
tract symptoms and incontinence.
AB - Up to 50% of heart failure patients suffer from lower urinary tract symptoms.
Urinary incontinence has been associated with worse functional status in patients
with heart failure, occurring three times more frequently in patients with New
York Heart Association Class III and IV symptoms compared with those with milder
disease. The association between heart failure and urinary symptoms may be
directly attributable to worsening heart failure pathophysiology; however,
medications used to treat heart failure may also indirectly provoke or exacerbate
urinary symptoms. This type of drug-disease interaction, in which the treatment
for heart failure precipitates incontinence, and removal of medications to
relieve incontinence worsens heart failure, can be termed therapeutic
competition. The mechanisms by which heart failure medication such as diuretics,
angiotensin-converting enzyme (ACE) inhibitors and beta-blockers aggravate lower
urinary tract symptoms are discussed. Initiation of a prescribing cascade,
whereby antimuscarinic agents or beta3-agonists are added to treat symptoms of
urinary urgency and incontinence, is best avoided. Recommendations and practical
tips are provided that outline more judicious management of heart failure
patients with lower urinary tract symptoms. Compelling strategies to improve
urinary outcomes include titrating diuretics, switching ACE inhibitors, treating
lower urinary tract infections, appropriate fluid management, daily weighing, and
uptake of pelvic floor muscle exercises.
PMID- 24357135
TI - Influence of urban residence on use of psychotropic medications in Pennsylvania,
USA: cross-sectional comparison of older adults attending senior centers.
AB - BACKGROUND: Differences in medication use by geographic region may indicate
differences in access to specialist medical care, especially in the case of
prescriptions for psychotropic medications. We assessed the effect of more or
less urbanized residence on likelihood of psychotropic medication use in a large
cohort of older adults in Pennsylvania, USA. METHODS: Community-dwelling older
adults were recruited from senior centers across Pennsylvania. Participant
residences were geocoded and categorized according to US Department of
Agriculture Rural-Urban Continuum Codes. We used the codes to identify
respondents who live in relatively urban counties with 250,000 or more residents
(n = 1,360) or less urban counties with fewer than 250,000 residents (n = 401).
Participants reported prescription medications in a clinical interview.
Psychotropic medications were categorized by class. Logistic regression models
were estimated to assess the independent effect of residence on likelihood of
psychotropic medication use. RESULTS: Geographic region was significantly
associated with use of psychotropic medications. Psychotropic medication use was
higher in less urban areas (19.7%) relative to more urban areas (14.2%), p =
0.007. In adjusted models, degree of urban residence was a significant correlate
in models that adjusted for sociodemographic features and medical status (odds
ratio 1.62; 95% confidence interval 1.13-2.31, p < 0.01). Use of psychotropic
medications on the Beers list also increased with less urban residence (13.0 vs.
8.3%, p = 0.005). CONCLUSIONS: Older adults living in less urbanized areas are
more likely to be prescribed psychotropic drugs. This difference may indicate a
health disparity based on access to geriatric specialists or mental health care.
PMID- 24357136
TI - Quantitative determination of myricetin in rat plasma by ultra performance liquid
chromatography tandem mass spectrometry and its absolute bioavailability.
AB - Myricetin is a widely distributed bioactive flavonoid with scientific interest
attributed to its anti-oxidant, antitumor, and anti-inflammatory properties. A
specific and sensitive ultra performance liquid chromatography-tandem mass
spectrometry (UPLC-MS/MS) method has been developed and validated for
identification and quantification of myricetin in rat plasma after oral and
intravenous administrations. Kaempferol was used as an internal standard.
Followed by beta-glucuronidase and sulfatase hydrolysis and liquid-liquid
extraction with ethyl acetate, the analytes were separated on an Acquity UPLC BEH
C18 column (2.1*50 mm, 1.7 MUm) and analyzed in the selected ion recording with a
negative electrospray ionization mode. The developed method was validated for
selectivity, accuracy, precision, linearity, recovery, stability and matrix
effect. The assay was validated over a wide concentration range of 2-4,000 ng/mL.
Intra- and inter-day precisions were all less than 13.49% and accuracy ranged
from 95.75 to 109.80%. The present method was successfully applied to investigate
a pharmacokinetic study of myricetin following intravenous and oral
administrations to rats. The absolute bioavailability was found to be 9.62% and
9.74% at 2 oral doses (50 mg/kg and 100 mg/kg, respectively), which indicated
myricetin was poorly absorbed after oral administration. To our knowledge, this
is the first pharmacokinetic evaluation of myricetin as a single active
pharmaceutical ingredient in preclinical studies.
PMID- 24357137
TI - Natural honey: a new and potent anti-angiogenic agent in the air-pouch model of
inflammation.
AB - Despite reports indicating anti-inflammatory effects of honey, the anti
angiogenic effect of honey and its impact on inflammatory mediators in the air
pouch model of inflammation have not yet been studied. The aims of present study
were to investigate the effects of honey on angiogenesis, inflammatory cytokine
vascular endothelial growth factor (VEGF) level as an important marker of
angiogenesis and prostaglandin E2 (PGE2) in the rat air pouch model of
inflammation. Male Wistar rats were anesthetized, and then 20 ml and 10 ml of
sterile air were injected subcutaneously in the back on days 0 and 3,
respectively. On day 6, inflammation was induced by injection of 1 ml of
carrageenan 1% into pouches. After 72 h, the rats were sacrificed; pouch fluid
was collected in order to determine PGE2 concentration and VEGF level. The
Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was
assayed using a hemoglobin kit. Honey was able to reduce granulation tissue
weight and angiogenesis as well as showing potent inhibitory activities against
PGE2 and VEGF in air pouch model of inflammation. The decrease in angiogenesis
correlates with the inhibition of PGE2 and VEGF. Honey is potentially useful in
the treatment of granulomatous inflammatory conditions. It seems that the anti
angiogenic activities of honey are mediated through modulation of PGE2 and VEGF
production.
PMID- 24357138
TI - Main metabolic pathways of TAK-802, a novel drug candidate for voiding
dysfunction, in humans: the involvement of carbonyl reduction by 11beta
hydroxysteroid dehydrogenase 1.
AB - To investigate species differences in the metabolism of TAK-802, in vitro and in
vivo metabolic profiles were compared between humans and animals. TAK-802 was
mainly metabolized to M-I, M-II, M-III and M-IV in human and animal liver
microsomes. Especially the M-IV formation in humans was greater than that in
animals. Likewise, M-IV was detected to a lower extent in the plasma and excreta
of animals administered with TAK-802, whereas the AUC0-48 h of M-IV was
approximately five-fold higher than that of TAK-802 in human plasma. These
results indicate that the in vitro metabolic profile reflects the in vivo
condition. Thus, to identify the metabolic pathway of TAK-802 in humans, the
responsible enzyme to form M-IV was elucidated in vitro. Since M-IV is a
reductive metabolite formed in microsomes, the possibility of involvement of
11beta-hydroxysteroid dehydrogenase (11beta-HSD), a carbonyl reductase located in
microsomes, was first investigated. Consequently, M-IV formation was confirmed by
incubation with human 11beta-HSD1-expressing microsomes and was concentration
dependently inhibited by glycyrrhetinic acid, an inhibitor for 11beta-HSD
enzymes, indicating the involvement of 11beta-HSD1 in the M-IV formation. In
contrast, little M-IV formation was observed using rat 11beta-HSD1, suggesting
species differences between humans and rats. In addition, M-II was formed via M
IV, not via M-I and the CYP identification studies revealed that both M-I
formation from TAK-802 and M-II formation from M-IV were mainly catalyzed by
CYP3A4. In conclusion, 11beta-HSD1 and CYP3A4 are principally responsible for the
metabolism of TAK-802 in humans and 11beta-HSD1 may be responsible for the
observed species difference.
PMID- 24357139
TI - Thyroid hormone modulates food intake and glycemia via ghrelin secretion in
Zucker fatty rats.
AB - Hyperthyroidism is known to increase food intake and central administration of
thyroid hormone shows acute orexigenic effects in rodents. We investigated
whether T3 influences appetite and glucose homeostasis by modulating circulating
ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute
anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained
for fasting induced food intake. The serum concentration of T3, ghrelin, glucose,
triglycerides, and liver glycogen were estimated. The involvement of sympathetic
nervous system was evaluated by conducting similar experiments in vagotomized
rats. T3 increased food intake and glucose in rats over 4 h, with increase in
serum T3 and decrease in liver glycogen. T3 treatment was associated with
increase in serum ghrelin. An additive effect on appetite and glucose was
observed when T3 (oral) was administered with central (intracerebroventricular)
administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a,
antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats,
T3 did not show increase in appetite as well as glucose. Serum ghrelin levels
were unchanged in these animals after T3 treatment. However, T3 showed increase
in serum triglyceride levels indicating its peripheral lipolytic effect, in
vagotomized as well as sham treated animals. To conclude, acute orexigenic and
hyperglycemic effects of T3 are associated with ghrelin secretion and activity.
This effect seems to be mediated via vagus nerves, and is independent of
glucoregulatory hormones.
PMID- 24357140
TI - Antimutagenic effects of vitamin E on oncology and non oncology hospital nurses
by comet assay.
AB - Vitamin E is a natural antioxidant and its most common biologically active form
is alpha-tocopherol. The antiproliferative effects of alpha-tocopherol have been
previously demonstrated. In this study the antimutagenic effects of vitamin E on
oncology and non oncology hospital nurses was investigated. A total of 138 female
nurses from oncology and non oncology hospitals participated in the study. They
received 200 mg/day vitamin E for 2 weeks. The urine samples before and after
intake of vitamin E were collected and the nucleus of urothelial cells were
evaluated with comet assay. The length of epithelial cells nuclei correlated with
increased fracture rate of DNA. Nucleolus length of urine epithelial cells of all
nursing staff before and after vitamin E treatment were measured and the data
were evaluated by student t-test and SPSS. Our study showed that 20% of nursing
staff have apoptosis and DNA fracture in the nucleolus of their urine epithelial
cells and DNA damage in the urothelial cells of exposed nurses was significantly
higher than the control group (P<0.05).The antimutagenic activity of vitamin E
had significant effects on oncology hospital nurses effectively in repairing DNA
damage and decreasing their nucleus length in urine epithelial cells.We propose
that the higher therapeutic doses of vitamin E and increasing the length of
treatment period will be effective against DNA strand breakage and may have more
effect on oncology nurses.
PMID- 24357141
TI - Effects of normal aging and SCN1A risk-gene expression on brain metabolites:
evidence for an association between SCN1A and myo-inositol.
AB - Previously reported MRS findings in the aging brain include lower N
acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and
choline-containing compound (Cho) concentrations. Alterations in the sodium
channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been
reported to be associated with several neurological disorders with cognitive
deficits. MRS studies in SCN1A-related diseases have reported striking
differences in the mI concentrations between patients and controls. In a study on
'healthy aging', we investigated metabolite spectra in a sample of 83 healthy
volunteers and determined their age dependence. We also investigated a potential
link between SCN1A and mI. We observed a significantly negative association of
NAA (p = 0.004) and significantly positive associations of mI (p <= 0.001), Cr (p
<= 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear
association of Cho ends at the age of about 50 years and is followed by an
inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the
SCN1A variant rs10930201. Our results corroborated the age-related changes in
metabolite concentrations, and found evidence for a link between SCN1A and
frontal white matter mI in healthy subjects.
PMID- 24357142
TI - Endoscopic cauterization of congenital pyriform fossa sinus tracts: an 18-year
experience.
AB - IMPORTANCE: Congenital pyriform fossa sinus tracts predispose to neck masses and
neck abscesses in pediatric and occasionally adult patients. Traditional
management involves open excision with substantial potential morbidity.
Endoscopic management allows an alternative, less morbid treatment approach.
OBJECTIVE: To evaluate the long-term effectiveness of endoscopic cauterization as
definitive treatment for pyriform fossa sinus tracts. DESIGN, SETTING, AND
PATIENTS: Retrospective review of the medical records of 23 children (aged 7
months to 14 years) with pyriform fossa sinus tracts treated with endoscopic
cauterization between 1995 and 2013 at a tertiary care children's hospital.
INTERVENTION: Endoscopic electrocauterization of pyriform fossa sinus tract
opening. MAIN OUTCOMES AND MEASURES: Recurrence of symptoms after endoscopic
treatment. RESULTS: Twenty-one of 23 patients experienced no recurrence after
their first endoscopic electrocauterization of the sinus tract. The 2 patients
with recurrence experienced symptoms within 1 month of cauterization and were
treated with either open excision or recauterization. Endoscopic cauterization
was able to definitively treat 9 patients whose treatments with incision and
drainage or open excision had failed. Mean (range) follow-up for the 15 patients
with follow-up was 7.4 (0.10-14.2) years. No procedure-related morbidity was
reported. CONCLUSIONS AND RELEVANCE: Endoscopic cauterization seems to be an
effective and potentially permanent treatment for congenital pyriform fossa sinus
tracts.
PMID- 24357143
TI - Compressive manifold learning: estimating one-dimensional respiratory motion
directly from undersampled k-space data.
AB - PURPOSE: To present and validate a manifold learning (ML)-based method that
estimates the respiratory signal directly from undersampled k-space data and that
can be applied for respiratory self-gated liver MRI. METHODS: ML methods embed
high-dimensional space data in a low-dimensional space while preserving their
characteristic properties. These methods have been used to estimate one
dimensional respiratory motion (low-dimensional manifold) from a set of high
dimensional free-breathing abdominal MR images. These approaches require MR
images to be reconstructed first from the acquired undersampled data. Recently,
the concept of compressive manifold learning (CML) has been introduced that
combines compressed sensing with ML by learning low-dimensional manifolds
directly from a partial set of compressed measurements, provided that the
sampling satisfies the restricted isometry property. We propose to use the CML
concept to extract the respiratory signal directly from undersampled k-space
data. RESULTS: Simulation results from free-breathing abdominal MR data show that
CML can accurately estimate respiratory motion from highly retrospectively
undersampled k-space (up to 25-fold acceleration under ideal assumptions).
Prospective free-breathing golden-angle radial two-dimensional (2D) acquisitions
further demonstrate the feasibility of the CML method for respiratory self-gating
acquisition, estimating the respiratory motion from up to 15-fold accelerated MR
data. CONCLUSION: The proposed method performs accurate respiratory signal
estimation from highly undersampled k-space data and can be used for respiratory
self-navigated 2D liver MRI.
PMID- 24357144
TI - Risedronate improves bone architecture and strength faster than alendronate in
ovariectomized rats on a low-calcium diet.
AB - Clinical evidence suggests that, compared with alendronate, risedronate reduces
fracture risk faster and more potently, with less bone mass gain. We tested the
hypothesis that risedronate improves bone quality faster than alendronate using
calcium-deficient, ovariectomized (OVX) rats. Female Sprague-Dawley rats at 24
weeks of age were divided into sham-operated and OVX groups and fed a low-calcium
(0.05%) diet under paired feeding. After 12 weeks, OVX rats were divided into
five groups and treated with vehicle, risedronate (3.5 and 17.5 MUg/kg/week,
s.c.) or alendronate (7 and 35 MUg/kg/week, s.c.). Rats were killed 6-8 weeks
later and the bone architecture and strength of the left femur were evaluated by
micro-computed tomography and a three-point bending test. Trabecular bone mineral
density (BMD), number and thickness were significantly lower in OVX rats than in
the sham-operated group. Cortical BMD, bone area (Ct.Ar), and thickness (Ct.Th)
were similarly decreased. Risedronate significantly improved Ct.Ar (+8%) and
Ct.Th (+9%) at 6 weeks, while alendronate only caused a significant improvement
in Ct.Ar (+8% at 6 weeks) and only at the higher dose. At 8 weeks, both
risedronate and alendronate significantly increased trabecular BMD compared with
the vehicle. Bone strength parameters showed a significant correlation between
Ct.Ar and Ct.Th. Risedronate significantly improved maximum load at 6 weeks,
while alendronate failed to produce any significant changes. Our results suggest
that risedronate is superior to alendronate at improving cortical bone
architecture and strength, and that enhanced bone quality partly accounts for
risedronate's efficacy.
PMID- 24357145
TI - Bioremediation of mine water.
AB - Caused by the oxidative dissolution of sulfide minerals, mine waters are often
acidic and contaminated with high concentrations of sulfates, metals, and
metalloids. Because the so-called acid mine drainage (AMD) affects the
environment or poses severe problems for later use, treatment of these waters is
required. Therefore, various remediation strategies have been developed to remove
soluble metals and sulfates through immobilization using physical, chemical, and
biological approaches. Conventionally, iron and sulfate-the main pollutants in
mine waters-are removed by addition of neutralization reagents and subsequent
chemical iron oxidation and sulfate mineral precipitation. Biological treatment
strategies take advantage of the ability of microorganisms that occur in mine
waters to metabolize iron and sulfate. As a rule, these can be grouped into
oxidative and reductive processes, reflecting the redox state of mobilized iron
(reduced form) and sulfur (oxidized form) in AMD. Changing the redox states of
iron and sulfur results in iron and sulfur compounds with low solubility, thus
leading to their precipitation and removal. Various techniques have been
developed to enhance the efficacy of these microbial processes, as outlined in
this review.
PMID- 24357146
TI - Type I interferons induced by radiation therapy mediate recruitment and effector
function of CD8(+) T cells.
AB - The need for an intact immune system for cancer radiation therapy to be effective
suggests that radiation not only acts directly on the tumor but also indirectly,
through the activation of host immune components. Recent studies demonstrated
that endogenous type I interferons (type I IFNs) play a role in radiation
mediated anti-tumor immunity by enhancing the ability of dendritic cells to cross
prime CD8(+) T cells. However, it is still unclear to what extent endogenous type
I IFNs contribute to the recruitment and function of CD8(+) T cells. Little is
also known about the effects of type I IFNs on myeloid cells. In the current
study, we demonstrate that type I and type II IFNs (IFN-gamma) are both required
for the increased production of CXCL10 (IP-10) chemokine by myeloid cells within
the tumor after radiation treatment. Radiation-induced intratumoral IP-10 levels
in turn correlate with tumor-infiltrating CD8(+) T cell numbers. Moreover, type I
IFNs promote potent tumor-reactive CD8(+) T cells by directly affecting the
phenotype, effector molecule production, and enhancing cytolytic activity. Using
a unique inducible expression system to increase local levels of IFN-alpha
exogenously, we show here that the capacity of radiation therapy to result in
tumor control can be enhanced. Our preclinical approach to study the effects of
local increase in IFN-alpha levels can be used to further optimize the
combination therapy strategy in terms of dosing and scheduling, which may lead to
better clinical outcome.
PMID- 24357147
TI - Enhanced therapeutic anti-tumor immunity induced by co-administration of 5
fluorouracil and adenovirus expressing CD40 ligand.
AB - Bystander immune activation by chemotherapy has recently gained extensive
interest and provided support for the clinical use of chemotherapeutic agents in
combination with immune enhancers. The CD40 ligand (CD40L; CD154) is a potent
regulator of the anti-tumor immune response and recombinant adenovirus (RAd)
mediated CD40L gene therapy has been effective in various cancer models and in
man. In this study we have assessed the combined effect of local RAd-CD40L and 5
fluorouracil (5-FU) administration on a syngeneic MB49 mouse bladder tumor model.
Whereas MB49 cells implanted into immunocompetent mice responded poorly to RAd
CD40L or 5-FU alone, administration of both agents dramatically decreased tumor
growth, increased survival of the mice and induced systemic MB49-specific
immunity. This combination treatment was ineffective in athymic nude mice,
highlighting an important role for T cell mediated anti-tumor immunity for full
efficacy. 5-FU up-regulated the expression of Fas and immunogenic cell death
markers in MB49 cells and cytotoxic T lymphocytes from mice receiving RAd-CD40L
immunotherapy efficiently lysed 5-FU treated MB49 cells in a Fas ligand-dependent
manner. Furthermore, local RAd-CD40L and 5-FU administration induced a shift of
myeloid-derived suppressor cell phenotype into a less suppressive population.
Collectively, these data suggest that RAd-CD40L gene therapy is a promising
adjuvant treatment to 5-FU for the management of bladder cancer.
PMID- 24357148
TI - Frequencies of circulating MDSC correlate with clinical outcome of melanoma
patients treated with ipilimumab.
AB - Metastatic melanoma has a poor prognosis with high resistance to chemotherapy and
radiation. Recently, the anti-CTLA-4 antibody ipilimumab has demonstrated
clinical efficacy, being the first agent to significantly prolong the overall
survival of inoperable stage III/IV melanoma patients. A major aim of patient
immune monitoring is the identification of biomarkers that predict clinical
outcome. We studied circulating myeloid-derived suppressor cells (MDSC) in
ipilimumab-treated patients to detect alterations in the myeloid cell compartment
and possible correlations with clinical outcome. Lin(-) CD14(+) HLA-DR(-)
monocytic MDSC were enriched in peripheral blood of melanoma patients compared to
healthy donors (HD). Tumor resection did not significantly alter MDSC
frequencies. During ipilimumab treatment, MDSC frequencies did not change
significantly compared to baseline levels. We observed high inter-patient
differences. MDSC frequencies in ipilimumab-treated patients were independent of
baseline serum lactate dehydrogenase levels but tended to increase in patients
with severe metastatic disease (M1c) compared to patients with metastases in skin
or lymph nodes only (M1a), who had frequencies comparable to HD. Interestingly,
clinical responders to ipilimumab therapy showed significantly less lin(-)
CD14(+) HLA-DR(-) cells as compared to non-responders. The data suggest that the
frequency of monocytic MDSC may be used as predictive marker of response, as low
frequencies identify patients more likely benefitting from ipilimumab treatment.
Prospective clinical trials assessing MDSC frequencies as potential biomarkers
are warranted to validate these observations.
PMID- 24357149
TI - Mosaic microdeletion of 17p11.2-p12 and duplication of 17q22-q24 in a girl with
Smith-Magenis phenotype and peripheral neuropathy.
AB - We report on a girl with a de novo mosaic derivative chromosome 17 involving a
7.4 Mb deletion of chromosome region 17p11.2 to 17p12 and a duplication of a
12.35 Mb region at 17q22 to 17q24. She was ascertained because of developmental
delay, peripheral neuropathy, brachydactyly and minor anomalies. The derivative
chromosome was present in approximately 12% of lymphocytes based on FISH studies,
and was detected by array comparative genomic hybridization. To our knowledge,
this is the third case of mosaicism involving deletion of the 17p11.2 region and
the lowest level of mosaicism reported in a patient with Smith-Magenis syndrome
(SMS).
PMID- 24357150
TI - Immunophenotypic comparison of heterogenous non-sorted versus sorted mononuclear
cells from human umbilical cord blood: a novel cell enrichment approach.
AB - Human umbilical cord blood (hUCB) has been the preferred source of stem cells for
the treatment of haematological malignancies and genetic disorders. This is
primarily due to its non-invasiveness, high accessibility with relative ease of
isolation. Still failures do prevail due to its heterogeneity and lesser
frequency of MSC identified in UCB. This study, thus, employs a cell enrichment
technology to improve its therapeutic efficacy. This was achieved by
immunophenotypic comparison of stem cells isolated from the heterogenous non
sorted mononuclear cells (MNCs), linage depleted (Lin+ and Lin-) fractions
obtained from magnetic activated cell sorter (MACS) and sorted MNCs obtained by
fluorescent activated cell sorter (FACS). The markers under consideration were
CD29, CD44, CD34, CD45, CD133, CD90 and CD117. FACS sorted MNCs were rich in
naive stem cell population, whereas non-sorted MNCs and lineage depleted
fractions were found to be rich in progenitors. Thus, we suggest that a
combination therapy of both sorted population might serve as an alternative
valuable tool in treating haematologic/genetic disorders. However, further
research on cell enrichment technology might give a clue for improved cell based
therapy in regenerative medicine.
PMID- 24357151
TI - Evaluation of acid-labile S-protecting groups to prevent Cys racemization in Fmoc
solid-phase peptide synthesis.
AB - Phosphonium and uronium salt-based reagents enable efficient and effective
coupling reactions and are indispensable in peptide chemistry, especially in
machine-assisted SPPS. However, after the activating and coupling steps with
these reagents in the presence of tertiary amines, Fmoc derivatives of Cys are
known to be considerably racemized during their incorporation. To avoid this side
reaction, a coupling method mediated by phosphonium/uronium reagents with a
weaker base, such as 2,4,6-trimethylpyridine, than the ordinarily used DIEA or
that by carbodiimide has been recommended. However, these methods are appreciably
inferior to the standard protocol applied for SPPS, that is, a 1 min
preactivation procedure of coupling with phosphonium or uronium reagents/DIEA in
DMF, in terms of coupling efficiency, and also the former method cannot reduce
racemization of Cys(Trt) to an acceptable level (<1.0%) even when the
preactivation procedure is omitted. Here, the 4,4'-dimethoxydiphenylmethyl and 4
methoxybenzyloxymethyl groups were demonstrated to be acid-labile S-protecting
groups that can suppress racemization of Cys to an acceptable level (<1.0%) when
the respective Fmoc derivatives are incorporated via the standard SPPS protocol
of phosphonium or uronium reagents with the aid of DIEA in DMF. Furthermore,
these protecting groups significantly reduced the rate of racemization compared
to the Trt group even in the case of microwave-assisted SPPS performed at a high
temperature.
PMID- 24357153
TI - Artificial gametes: perspectives of geneticists, ethicists and representatives of
potential users.
AB - Several threads of research towards developing artificial gametes are ongoing in
a number of research labs worldwide. The development of a technology that could
generate gametes in vitro has significant potential for human reproduction, and
raises a lot of interest, as evidenced by the frequent and extensive media
coverage of research in this area. We have asked researchers involved in work
with artificial gametes, ethicists, and representatives of potential user groups,
how they envisioned the use of artificial gametes in human reproduction. In the
course of three focus groups, the participants commented on the various aspects
involved. The two recurring themes were the strength of the claim of becoming a
parent genetically, and the importance of responsible communication of science.
The participants concurred that (a) the desire or need to have genetic offspring
of one's own does not warrant the investment of research resources into these
technologies, and that (b) given the minefield in terms of moral controversy and
sensitivity that characterises the issues involved, how information is
communicated and handled is of great importance.
PMID- 24357154
TI - Fryns syndrome without diaphragmatic hernia, DOOR syndrome or Fryns-like
syndrome? Report on patients from Indian Ocean islands.
AB - We report on six patients (five unpublished patients) from the Indian Ocean
islands, with coarse face, cleft lip or palate, eye anomalies,
brachytelephalangy, nail hypoplasia, various malformations (genitourinary or
cerebral), abnormal electroencephalograms with impaired neurological examination
and lethal outcome. Massive polyhydramnios was noted in the third trimester of
pregnancy and neonatal growth was normal or excessive. The combination of the
features is consistent with the diagnosis of Fryns syndrome (FS) without
congenital diaphragmatic hernia. Besides chromosomal aberrations and
microdeletion syndrome, differential diagnoses include conditions overlapping
with FS such as Simpson-Golabi-Behmel, and conditions with hypoplasia/absence of
the distal phalanges such as DOOR syndrome, Schinzel-Giedion syndrome, and
Rudiger syndrome.
PMID- 24357155
TI - Antidepressant use among survivors of childhood, adolescent, and young adult
cancer: letter to the editor response.
PMID- 24357156
TI - A physics-based algorithm for real-time simulation of electrosurgery procedures
in minimally invasive surgery.
AB - BACKGROUND: High-frequency electricity is used in the majority of surgical
interventions. However, modern computer-based training and simulation systems
rely on physically unrealistic models that fail to capture the interplay of the
electrical, mechanical and thermal properties of biological tissue. METHODS: We
present a real-time and physically realistic simulation of electrosurgery by
modelling the electrical, thermal and mechanical properties as three iteratively
solved finite element models. To provide subfinite-element graphical rendering of
vaporized tissue, a dual-mesh dynamic triangulation algorithm based on isotherms
is proposed. The block compressed row storage (BCRS) structure is shown to be
critical in allowing computationally efficient changes in the tissue topology due
to vaporization. RESULTS: We have demonstrated our physics-based electrosurgery
cutting algorithm through various examples. Our matrix manipulation algorithms
designed for topology changes have shown low computational cost. CONCLUSIONS: Our
simulator offers substantially greater physical fidelity compared to previous
simulators that use simple geometry-based heat characterization.
PMID- 24357157
TI - Expressions of CD147, MMP-2 and MMP-9 in laryngeal carcinoma and its correlation
with poor prognosis.
AB - The objectives of this study are to investigate the expressions of matrix
metalloproteinase inducing factor (CD147), matrix metalloproteinase-2 (MMP-2),
matrix metalloproteinase-9 (MMP-9) in laryngeal tumor tissues and its significant
correlation with tumor infiltration, metastasis and prognosis. Laryngeal tumor
tissue from 48 laryngeal cancer patients with complete clinical information was
collected. The laryngitis tissue from 15 patients were collected as control
group. Immunohistochemical analysis for CD147, MMP-2 and MMP-9 was performed for
all the tissue. The results showed the expression rates of CD147, MMP-2 and MMP-9
in laryngeal carcinoma were 87.5 %, 75.0 % and 79.2 % respectively, significantly
higher than those (26.7 %, 6.7 %, and 33.3 % respectively) in the control group
are (P < 0.01). High expression of CD147, MMP-2 and MMP-9 related to the clinical
stages and lymphatic metastasis of laryngeal carcinoma. Univariate survival
analysis showed that the 5-year survival of laryngeal carcinoma patients with low
expression of CD147, MMP-2 and MMP-9was 83.3 %, 83.3 % and 90 % respectively,
while the patients with high expression had 5-year survival at 25 %, 7.7 % and
18.2 % respectively (P < 0.05). Multiple regression analysis showed that high
expression of MMP-9 was independently associated with poor prognosis (P < 0.05).
High expression of CD147, MMP-2 and MMP-9 were related with laryngeal carcinoma
invasion and metastasis. High expressions of CD147, MMP-2 and MMP-9 were all
predictive factors of poor prognosis of laryngeal carcinoma.
PMID- 24357159
TI - Clinicopathological features and prognosis of pregnancy associated breast cancer
a matched case control study.
AB - Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a
year following delivery. We sought to investigate differences in management,
outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics
of PABC and matched controls in a retrospective case control study. PABC and
control patients were selected from breast cancer cases of women <=45 years,
diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest,
Hungary between 1998 and 2012. Histopathology information on tumor type, grade,
size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI),
associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were
recorded, IHC-based subtype was assessed, clinical, management and outcome data
were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical
management data did not differ in cases and controls. Histopathology of disease
at presentation was not significantly different, but NPI assessed the PABC group
as having poor, whereas controls as having intermediate prognosis. Associated in
situ lesion was more often high grade Extensive Intraductal Carcinoma Component
(EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC.
Disease-free and overall survival was inferior compared to controls. PABC
patients with LuminalB prol and Triple negative tumors had inferior outcomes. On
multivariate analysis inferior prognosis of PABC was associated with pregnancy.
Our study has demonstrated inferior outcome of PABC. Difference in tumor biology
is reflected by the predominance of triple negative and LuminalB tumors in PABC.
The strength of the study is the analysis of complete pathology and IHC data.
PMID- 24357160
TI - Review of models used in economic analyses of new oral treatments for type 2
diabetes mellitus.
AB - BACKGROUND: Economic models are considered to be important, as they help evaluate
the long-term impact of diabetes treatment. To date, it appears that no article
has reviewed and critically appraised the cost-effectiveness models developed to
evaluate new oral treatments [glucagon-like peptide-1 (GLP-1) receptor agonists
and dipeptidyl peptidase-4 (DPP-4) inhibitors] for type 2 diabetes mellitus
(T2DM). OBJECTIVES: This study aimed to provide insight into the utilization of
cost-effectiveness modelling methods. The focus of our study was aimed at the
applicability of these models, particularly around the major assumptions related
to the clinical parameters (glycated haemoglobin [A1c], systolic blood pressure
[SBP], lipids and weight) used in the models, and subsequent clinical outcomes.
METHODS: MEDLINE and EMBASE were searched from 1 January 2004 to 14 February 2013
in order to identify published cost-effectiveness evaluations for the treatment
of T2DM by new oral treatments (GLP-1 receptor agonists and DPP-4 inhibitors).
Once identified, the articles were reviewed and grouped together according to the
type of model. The following data were captured for each study: comparators;
country; evaluation and key cost drivers; time horizon; perspective; discounting
rates; currency/year; cost-effectiveness threshold, sensitivity analysis; and
cost-effectiveness analysis curves. RESULTS: A total of 15 studies were
identified in our review. Nearly all of the models utilized a health care payer
perspective and provided a lifetime horizon. The CORE Diabetes Model, UK
Prospective Diabetes Study (UKPDS) Outcomes Model, Cardiff Diabetes Model,
Centers for Disease Control and Prevention (CDC) Diabetes Cost-Effectiveness
Group Model and Diabetes Mellitus Model were cited. With the exception of two
studies, all of the studies made significant assumptions surrounding the impact
of GLP-1 receptor agonists or DPP-4 inhibitors on clinical parameters and
subsequent short- and long-term outcomes. Moreover, often the differences in the
clinical parameters were relatively small (e.g. 1 or 2 mmHg in blood pressure)
and would not be considered by many as clinically important. Yet, the impact of
these small clinical changes often resulted in large lifetime changes in health
outcomes in the models. In particular, many studies assumed that changes in
weight associated with the therapies would equate to improved outcomes, despite
limited evidence for this assumption. Although the new oral treatments were
regarded as cost effective in most studies based upon the studies reviewed, the
validity of these projections, particularly for the longer time frames, is
questionable. Indeed, although most of these studies have been conducted in the
last 5 years, recent trial evidence has already questioned the validity of most
of these studies. CONCLUSION: It is clear that a number of changes are required
in the evaluation of diabetes therapies. First and foremost, the basic models
need to be updated to include contemporary important clinical trial data
assessing hard clinical outcomes in patients with diabetes. Second, there should
be less emphasis on 40-year or lifetime costs and consequences of the therapies
and a greater focus on short-term (5-year) and intermediate-term (10-year)
outcomes. Practice is continually evolving, and the probability that these models
would provide any valid predictions beyond 10 years is remote. Third, all
modellers should immediately remove the basic assumption that small clinically
inconsequential changes in A1c, SBP, lipids and weight result in major clinical
improvements in patients. Future models should aim to include all relevant
treatment outcomes, whether these relate to effects on underlying diabetes and
its complications or to short- or long-term side effects of treatment. We need to
explore why cost-saving interventions could benefit further from adding patient
characteristics, which may be able to better predict the use of lower-cost
alternatives. Moreover, the vast array of different clinical, cost and utility
data used in the different models reviewed makes it apparent that a uniform
methodology should be developed for diabetes economic models. In this manner,
future models could be run using the same data, which would allow for more
acceptable comparability between studies.
PMID- 24357161
TI - A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis
in non-small-cell lung cancer.
AB - In more recent years, long non-coding RNAs (lncRNAs) have been investigated as a
new class of regulators of cellular processes, such as cell growth, apoptosis,
and carcinogenesis. Although lncRNAs are dysregulated in numerous cancer types,
limited data are available on the expression profile and functional role of
lncRNAs in non-small cell lung cancer (NSCLC). In the present study, we
determined the expression pattern of the growth arrest-specific transcript 5
(GAS5) in 72 NSCLC specimens by qRT-PCR and assess its biological functions in
the development and progression of NSCLC. The results revealed that GAS5
expression was down-regulated in cancerous tissues compared to adjacent
noncancerous tissues (P < 0.05) and was highly related to tumor size and TNM
stage (P < 0.05). This correlation between GAS5 and clinicopathological
parameters indicates that GAS5 might function as a tumor suppressor. Furthermore,
GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in
vitro and in vivo. Meanwhile, siRNA-mediated knockdown of GAS5 promoted tumor
cell growth. Importantly, through western blot analysis, we found that ectopic
expression of GAS5 significantly up-regulated p53 expression and down-regulated
transcription factor E2F1 expression. Taken together, these findings suggest that
GAS5 is a tumor suppressor in NSCLC, and the action of GAS5 is mediated by p53
dependent and p53-independent pathways. GAS5 could serve as a potential
diagnostic marker for NSCLC and may be a novel therapeutic target in patients
with NSCLC.
PMID- 24357158
TI - Stimuli-induced organ-specific injury enhancement of organotropic metastasis in a
spatiotemporal regulation.
AB - The relationship between inflammation and tumorigenesis has been established.
Recently, inflammation is also reported to be a drive force for cancer
metastasis. Further evidences show that various stimuli directly induced-injury
in a specific organ can also promote metastasis in this organ, which include
epidemiological reports, clinical series and experimental studies. Each type of
cancer has preferential sites for metastasis, which is also due to inflammatory
factors that are released by primary cancer to act on these sites and indirectly
induce injuries on them. Host factors such as stress,fever can also influence
distant metastasis in a specific site through stimulation of immune and
inflammatory effects. The five aspects support an idea that specific-organ injury
directly induced by various stimuli or indirectly induced by primary tumor or
host factors activation of proinflammatory modulators can promote metastasis in
this organ through a spatiotemporal regulation, which has important implications
for personalized prediction, prevention and management of cancer metastasis.
PMID- 24357162
TI - Optimal coronary artery bypass grafting strategy for acute coronary syndrome.
AB - OBJECTIVE: Conventional coronary artery bypass grafting (CABG) using
cardiopulmonary bypass and cardiac arrest is associated with higher mortality and
morbidity rates in acute coronary syndrome (ACS) patients undergoing surgery.
Although off-pump CABG (OPCAB) is beneficial for high-risk patients, its efficacy
for ACS is unknown, with on-pump beating CABG an adjunctive method. We
investigated the effects of OPCAB and on-pump beating CABG for ACS. METHODS: We
evaluated 121 consecutive patients with ACS (91 males, 30 females; mean age 69.5
+/- 10.3 years) who underwent CABG since 2000. Seventy-five had unstable angina
(UA) and 46 acute myocardial infarction (AMI) [non-ST elevation (NSTEMI): 22, ST
elevation (STEMI): 24]. We assessed CABG for acute coronary syndrome under our
primary OPCAB strategy, and compared perioperative status between UA and AMI
patients. RESULTS: (1) Sixty-five (87 %) with UA underwent OPCAB, 8 on-pump
beating CABG, and 2 conventional CABG. Conversion from OPCAB was seen in 4
patients. In-hospital mortality was 1.3 %. (2) All UA patients who had intra
aortic balloon pumping (IABP) underwent OPCAB. No patients with preoperative IABP
experienced conversion from OPCAB. (3) In AMI patients, hospital mortality was
higher (8.9 %) and the ratios for OPCAB, on-pump beating CABG, and conventional
CABG were 39, 57, and 4 %, respectively. Mortality was exclusively seen in
patients with STEMI who underwent conventional CABG. CONCLUSIONS: OPCAB might
have beneficial effects for ACS patients with UA, while IABP was found essential
for completing OPCAB. In AMI patients, on-pump beating CABG might be reasonable
for avoiding conversion from OPCAB and ischemic perfusion injury.
PMID- 24357163
TI - Chitosan nanoparticles are efficient carriers for delivering biodegradable drugs
to neuronal cells.
AB - Chitosan nanoparticles (NPs) are biocompatible drug carriers able to cross the
blood-brain barrier and represent a promising drug delivery system to the central
nervous system. We used chitosan NPs to deliver the D-Ala2-D-Leu5-enkephalin
(DADLE) to neuronal cells in vitro. DADLE is a hypometabolising synthetic opioid
potentially useful for biomedical applications, but its short plasmatic half-life
makes its in vivo administration ineffective. Here, we demonstrate by
immunoelectron microscopy that (1) chitosan NPs are capable to deliver the opioid
to neuronal cells; (2) DADLE is released from the internalised, opioid-loaded NPs
up to 48 h; (3) in the nucleus, DADLE binds the transcription/splicing sites; (4)
cells treated with DADLE-loaded NPs undergo a decrease in transcription factor
amounts and proliferation rate without damage to cell organelles. In this model,
chitosan NPs protected the loaded opioid from degradation, thereby prolonging its
intracellular effects. These findings suggest that these NPs are efficient for
the systemic and tissue administration of opioids in vivo.
PMID- 24357164
TI - A novel post-ligation thioesterification device enables peptide ligation in the N
to C direction: synthetic study of human glycodelin.
AB - Human glycodelin consists of 162 amino acid residues and two N-linked glycans at
Asn(28) and Asn(63) . In this study, we synthesized it by a fully convergent
strategy using native chemical ligation (NCL) in N to C direction. The four
peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were
synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. At
the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was
attached as a post-ligation thioesterification device. The N-terminal two
segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the
product was methylated to convert homocysteine to methionine. After deprotection
of acetamidomethyl group on the N-ethylcysteine residue, the peptide was
thioesterified by N-alkylcysteine-assisted method. The product was then ligated
with the C-terminal half, which was obtained by the NCL of third and fourth
segments, to give the full-length glycodelin.
PMID- 24357165
TI - [Epidemiological cancer registration in Germany: an impressive research
resource].
PMID- 24357166
TI - [Epidemiological cancer registries in Germany: history from a legal point of
view].
AB - Despite decades of efforts, the establishment of a satisfactory nationwide,
population-based cancer registry for Germany was very slow. The reason for this
until 1990 was the lack of coverage or the-apart from the Saarland-inadequate
degree of coverage in the old federal states. The former East Germany, however,
had a comprehensive cancer registry. Starting in 1990, decisive obstacles
especially when considering data protection needs and the distribution of powers
between federal and state governments-could be overcome. On the basis of an open
ended federal law and state requirements, a nationwide cancer registry with
analysis of the collected data for epidemiological purposes has been achieved.
PMID- 24357167
TI - [Nationwide statements from regional data: methods of the Center for Cancer
Registry Data].
AB - Despite having achieved nationwide registry coverage in addition to substantial
improvements in data on the epidemiology of cancer in Germany, the Centre for
Cancer Registry Data continues to estimate national statistics on incidence,
survival, and prevalence instead of calculating these directly from available
data. The methods used for evaluations are based initially on estimates of
registration completeness or, for survival analyses, an assessment of the quality
of follow-up data. The completeness of incident case registration is estimated on
the basis of the mortality/incidence procedure, which assumes a largely constant
relationship between the mortality and incidence of a cancer type among people of
the same age and sex across federal states. Inclusion criteria for consideration
of registry data in national survival analyses are less than 15% of death
certificate only (DCO) cases and plausible survival for patients with pancreatic
cancer or metastatic lung cancer. Of the 477,300 incident cancer cases estimated
for 2010, 429,900 were reported by the cancer registries (90%), and ten federal
states contributed data to national survival estimates.
PMID- 24357168
TI - [Epidemiological cancer data online: an overview of information service in
Germany and Europe].
AB - Finding reliable data about cancer epidemiology on the World Wide Web is not an
easy task. Information is often scattered, and sources are not always clear. This
article gives a short overview of the most important websites that provide
reliable data for Germany and Europe. Four internet sites are presented: The
German Centre for Cancer Registry Data (ZfKD), the Association of Population
Based Cancer Registries in Germany (GEKID), and two different websites created by
the International Agency for Research on Cancer (IARC). In combination, they
provide comprehensive information about the distribution of cancer in Germany and
Europe.
PMID- 24357169
TI - [Clinical and epidemiological cancer registries: two complementary sources of
information on cancer incidence].
AB - The law for the development of early cancer detection and quality assurance by
clinical cancer registries regulates the duties, the funding, and the functions
of the clinical cancer registries and thereby the cooperation between
epidemiological and clinical registries. The necessary regulations and interfaces
are described here. The progress in new concepts of cancer registration is
triggered by fundamental changes in oncological care such as the increasing use
of high-quality guidelines and the certification of oncological health-care
units.
PMID- 24357170
TI - [Active surveillance of small-scale spatial cancer clusters: presentation of a
new monitoring approach for the epidemiological Cancer Registry of Lower Saxony].
AB - BACKGROUND: Cancer registries often receive inquiries on possible cancer
clusters. In 2010, the Cancer Registry of Lower Saxony reported on a spatial
leukemia accumulation in the community of Asse. As a result, the Cancer Registry
was engaged in developing an approach for a regional cancer monitoring program by
the federal government. The modular approach involves a two-stage process. First,
all regional monitoring areas are under surveillance, and in the second phase,
noticeable areas only are observed further. A positive confirmation test is
regarded as an initial concern and may lead to further investigations. METHODS:
The standardized incidence ratio (SIR) is used in the first stage. For
confirmation, the Sequential Probability Ratio Test (SPRT) is applied in the
second stage. All new observations are tested at a given time. The SPRT tests the
null hypothesis (no increase) and an alternative hypothesis (increase) leading to
three possible conclusions: warning, all-clear, or further surveillance
necessary. RESULTS: A high false alarm rate due to clustering by chance is to be
considered with multiple statistical testing. The number of false alarms depends
on the number of tested areas, diagnoses, subgroup analyses, and time periods.
Preliminary considerations comprise 400 spatial areas, three diagnosis groups, no
subgroup analyses, and a biannual first-stage testing. Guidelines for the level
of significance and for detecting an increase in incidence will be necessary for
the assessment of the monitoring parameters. DISCUSSION: Before running the
monitoring program, a number of questions have to handled politically; e.g., how
many false alarms can be handled, the impact on the population involved, and
existing risk communication structures.
PMID- 24357171
TI - [Active monitoring of cancer clusters: comments from an epidemiological
perspective].
AB - Epidemiological cancer registries are responsible for the description of the
occurrence of cancers in time and space in the respective Federal State(s). Their
work also involves the work-up of suspected or obvious regional clusters of
cancer cases. The current sequence of action - (a) to confirm the cluster by a
statistical test, (b) to identify specific exposures as potential causes, (c) to
potentially conduct etiologic-epidemiological studies to confirm a suspected
association - fails because of methodological difficulties. This article outlines
a different approach that focuses on (a) the explanation of these methodological
limitations and (b) on the current epidemiological knowledge on cancer etiology
in order to rule out misunderstandings on potential causes of cancer clusters.
Collaboration with professional cancer registries is advised.
PMID- 24357172
TI - [Epidemiological research with data from cancer registries: a program financed by
the German Cancer Aid (Deutsche Krebshilfe, DKH)].
AB - In 2007, the German Cancer Aid started a program to promote epidemiological
research with data from cancer registries. Within this program, ten projects with
various epidemiological research questions were funded. The program was a major
boost for the use of data from population-based cancer registries and was an
important milestone for cancer epidemiology in Germany.
PMID- 24357173
TI - [Cohort study of cancer incidence in patients with type 2 diabetes: record
linkage of encrypted data from an external cohort with data from the
epidemiological Cancer Registry of North Rhine-Westphalia].
AB - INTRODUCTION: German epidemiologic cancer registries may store only encrypted
personal identifiers. Thus, record linkage with secondary databases needs to be
performed via procedures that are based on encrypted identifiers. In this paper,
we describe the linkage of patient data from a statutory health insurance company
(AOK NordWest) and from the Disease Management Program for diabetes mellitus type
2 with the database of the cancer registry. We report the cancer incidence in
patients with type 2 diabetes (T2D). METHODS: Personal identifying variables of
the patient cohort were encrypted before being sent electronically to the cancer
registry and submitted to a probabilistic record linkage with registry data. The
study included T2D patients who were residents of the Munster, Detmold, or
Arnsberg districts and who were aged 40-79 years. Only primary cancers occurring
between the date of enrolment and the censoring date (31 December 2010) were
included. The standardized incidence ratio (SIR) was calculated relative to the
number of incident cases expected on the basis of the averaged incidence rates in
the general population. RESULTS: The record linkage took about 3 weeks of
processing time. A total of 67,447 T2D (49.2 % men) cases were included for
analyses. Incident cancer was diagnosed in 2,086 men and 1,578 women. Cohort
members showed an elevated risk for cancer of the liver (SIR =1.86; 95% CI =1.47
2.31), pancreas (SIR = 1.62; 95 % CI =1.36-1.91), lung (SIR = 1.21; 95% CI 1.11
1.32), and uterus (SIR = 1.34; 95 % CI 1.08-1.65), and they were less likely to
be diagnosed with prostate cancer (SIR =0.72; 95% CI = 0.65-0.79). DISCUSSION:
The findings of this study suggest that record linkage of secondary databases
with cancer registry data for research purposes can be effectively carried out in
compliance with strict data-protection regulations.
PMID- 24357174
TI - [Evaluation of the impact of the mammography screening program on breast cancer
mortality: feasibility study on linking several data sources in North Rhine
Westphalia].
AB - BACKGROUND: In the German Mammography Screening Program (MSP), women aged 50-69
years are offered X-ray-based mammography for the early detection of breast
cancer (BC) every 2nd year. To maintain the licensing of the MSP, evidence of a
positive benefit-risk assessment of the radiation-related health risk has to be
provided. Therefore, long-term effects of the program have to be shown by
evaluating the BC mortality reduction based on the MSP. A current feasibility
study attempts to develop different data flow models to evaluate whether, based
on current legislations on data confidentiality, secondary data routinely
available in the German health system can be linked in such a way that they can
be used for epidemiological evaluation studies. We present the"NRW model," which
builds on procedures developed and evaluated in the Epidemiological Cancer
Registry of North Rhine-Westphalia (EKR-NRW). METHODS: Data of the Association of
Statutory Health Physicians in Westfalen-Lippe (KVWL) are used to enumerate the
cohort of women in WL who are entitled to MSP participation and their use of
curative mammography outside of the MSP. The EKR-NRW provides epidemiological and
medical data on all BC cases in WL, on cohort mortality, and on causes of death.
The central MSP database MaSc offers the screening history of all MSP
participants. The established uniform encryption methods employed in the EKR-NRW
are used for linking records from the three data sources in one data-merging
center (DZS). To this end, data are first captured in standardized formats,
variably aggregated and transferred in an encrypted format, checked for anonymity
and diversity level in an encrypted form, and eventually stored in a factually
anonymized manner in the evaluation center (ES). Researchers can obtain data sets
with plain text epidemiological-medical data from the ES for analyses.
PMID- 24357175
TI - [Determination of interval cancer rates in the German mammography screening
program using population-based cancer registry data].
AB - GOAL: The evaluation of interval cancers (ICA) and false-negative diagnoses (FND)
is important for the quality assurance of the mammography screening program (MSP)
for women aged 50-69 years. We aimed to investigate ICA in the states of Lower
Saxony (NDS) and North Rhine-Westphalia (NRW). ICA could be identified by record
linkage of data from screening attendees (TN) with data from population-based
cancer registries. The frequencies of ICA and FND are described, and problems in
the categorization of ICA according to EU guidelines are discussed. METHODS:
Record linkage in the cancer registries was performed with the encrypted data
from 83,724 TN in NDS and 885,940 TN in NRW. ICA were identified; in NDS, ICA
were categorized by the regional MSP reference center. RESULTS: In all, 208 ICA
in NDS and 2.018 ICA in NRW were ascertained. In relation to the regional
background incidence rate (IR), the relative ICA rates were 22.5%/26.7% in the
first year after screening (recommendation of EU guidelines <30% of IR) and
55.6%/54.2% in the second year after screening (recommendation of EU guidelines
<50% of IR). It was found that 17.3% of all categorized ICA in NDS were FND
(recommendation of EU guidelines <20%). DISCUSSION: The relative ICA rates for
the 2-year interval are consistent with the recommendations of the EU guidelines.
Unlike in NDS, the categorization of ICA was not possible in NRW. The MSP needs
the diagnostic mammograms of all ICA in order to identify FND. However, data
protection regulations are hindering this process and nationwide comparability of
FND is therefore not guaranteed. In NDS, the state government has enacted laws to
facilitate the transfer of diagnostic mammograms to the MSP. There is need for
this sort of action in other federal states too.
PMID- 24357176
TI - [Incidence of melanoma and changes in stage-specific incidence after
implementation of skin cancer screening in Schleswig-Holstein].
AB - A pilot project in skin cancer screening (SCREEN) was conducted in Schleswig
Holstein from July 2003 to June 2004. Although the impact of this screening on
the stage-specific incidence of melanoma is of great importance for screening
evaluation, it remains unknown. In theory, an effective skin cancer screening
program should result in a medium-term incidence decrease of melanomas with a
prognostically unfavorable stage. This is studied on a population-based level by
using cancer registry data. Based on data from the Cancer Registry of Schleswig
Holstein for 1999-2009, stage-specific (T-category of the TNM-classification
system) age-standardized incidence rates were calculated. After implementation of
the SCREEN project, the incidence of prognostically favorable melanomas (in situ
and T1) was higher than before, while the incidence of advanced melanomas (T2,
T3, and for women also T4) decreased considerably. The classification of tumor
stages changed during the project period, which may have contributed to an
artificial decrease of the stages with a poor prognosis. Nevertheless, the
results are in agreement with the observed decrease of melanoma mortality in the
screening region.
PMID- 24357177
TI - [Rising incidence of papillary thyroid carcinoma in Germany].
AB - BACKGROUND: The incidence of thyroid cancer (TC), a rare malignancy, has strongly
risen in recent decades. Possible causes of this rise include increasing
diagnostic activity, nuclear tests after World War II, and the Chernobyl
disaster. AIM: This article presents the time trends of TC incidence between 2003
and 2008 in Germany according to histological tumor type and sex, and provides a
description of TC incidence according to districts (Kreise) and sex in Germany.
METHODS: Data on persons newly diagnosed with thyroid cancer (ICD-10 code, C73)
between 2003 and 2008 were obtained from the Center of Cancer Registry Data at
the Robert Koch Institute. Official population and mortality data were used. Age
specific and age-standardized incidence rates (ASIR) were calculated according to
sex and tumor histology. RESULTS: Between 2003 and 2008, the ASIR of TC rose from
2.7 to 3.4 (men) and from 6.5 to 8.9 (women) per 100,000 per year. This rise can
be almost completely attributed to the rising incidence of papillary TC. The
steepest rise in frequency was observed in TNM-T1 tumors. A positive north-south
gradient of TC incidence was found. DISCUSSION: The cause of the marked rise of
TC incidence in recent decades is unknown. The positive north-south gradient of
the TC incidence may possibly be attributed in part to long-standing differences
of iodine intake between different German regions. CONCLUSION: An epidemiological
study of the possible causes of the rising TC incidence and of the regional
differences of TC incidence in Germany is recommended.
PMID- 24357178
TI - [Leukemia incidence and survival in Germany according to current standardized
categories].
AB - BACKGROUND: Leukemias include a large number of diverse malignancies concerning
the blood-forming system. Population-based comparisons and time trends are
complicated by inconsistent definitions and classifications. In the course of the
European HAEMACARE project, a consensus grouping system was created based on the
morphology codes of the ICD-O-3 (International Classification of Diseases
Oncology, third revision), consistent with the WHO classification published in
2008 and useful for epidemiologic and public health purposes. For the first time
leukemia incidence and survival in Germany are presented according to this system
on the basis of cancer registry data.. MATERIAL AND METHODS: A set of leukemia
cases diagnosed during 2001-2010 was extracted from the data submitted by German
population-based cancer registries to the Robert Koch Institute in early 2013 and
grouped according to the HAEMACARE system. Direct age-standardized incidence
rates were calculated. To estimate the prognosis of adult leukemia patients
diagnosed during 2008-2010, the 5-year relative survival was computed using the
period approach. RESULTS AND DISCUSSION: Based on 23,328 predominantly leukemic
malignancies ascertained for six federal states over a 10-year period, the age
standardized incidence rates were 4.1 (per 100,000) for chronic lymphocytic
leukemia, 3.1 for acute myeloid leukemia, and 2.4 for myeloproliferative
neoplasms, similar to other European regions. The 5-year relative survival of
leukemia in Germany currently ranges between 8 and 95% according to sex, age, and
category, and is thus considerably better compared with results derived from a
European data pool referring to 2000-2002.
PMID- 24357179
TI - [The future incidence of colorectal and lung cancers: results of the calculation
of different scenarios for the year 2020].
AB - BACKGROUND: Cancer is a common disease that places a large burden on health-care
systems. Although the rise of incident cancer cases over recent decades in
Germany can largely be explained by demographic ageing, other factors also affect
these numbers. The aim of this work was to calculate the incidence of colorectal
and lung cancers, two of the most common cancer sites, for the year 2020 under
different scenarios. MATERIALS AND METHODS: The calculations were based on
national incidence estimates by the Centre for Cancer Registry Data at the Robert
Koch Institute. Two scenarios were calculated for each of the two cancer sites
and by gender. The "status quo" scenario accounts only for demographic ageing,
assuming constant age-specific incidence rates. The second scenario additionally
assumes that trends in incidence rates observed from 2000 to 2009 continue up to
the year 2020. RESULTS: The "status quo" scenarios showed an increase in incident
cancer cases of between 12 and 24%, depending on gender and cancer site. The
"continuing trends" scenarios resulted in smaller increases for colorectal cancer
(+3 to + 17%), while the results for lung cancer differed widely between women (+
64%) and men (+ 2%). In general, large increases are expected for the highest age
groups and the age groups of the baby boomer generation. DISCUSSION: Changes in
the age structure of the German population will lead to an increase in incident
cancer cases and a higher portion of geriatric patients. Additionally, further
increasing incidence rates would result in a dramatic growth in the number of
female lung cancer patients.
PMID- 24357181
TI - Methods to enable the design of bioactive small molecules targeting RNA.
AB - RNA is an immensely important target for small molecule therapeutics or chemical
probes of function. However, methods that identify, annotate, and optimize RNA
small molecule interactions that could enable the design of compounds that
modulate RNA function are in their infancies. This review describes recent
approaches that have been developed to understand and optimize RNA motif-small
molecule interactions, including structure-activity relationships through
sequencing (StARTS), quantitative structure-activity relationships (QSAR),
chemical similarity searching, structure-based design and docking, and molecular
dynamics (MD) simulations. Case studies described include the design of small
molecules targeting RNA expansions, the bacterial A-site, viral RNAs, and
telomerase RNA. These approaches can be combined to afford a synergistic method
to exploit the myriad of RNA targets in the transcriptome.
PMID- 24357182
TI - Distinct effects of nuclear volume fraction and cell diameter on high b-value
diffusion MRI contrast in tumors.
AB - PURPOSE: While many recent studies have demonstrated improved detection and
characterization of malignant lesions using high b-value diffusion imaging
techniques, little is known about the underlying physical characteristics of
tumor cells that modulate the restricted water signal at high b on clinical
scanners. METHODS: Monte Carlo simulations of diffusion in a synthetic tumor cell
environment were used to study the specific effects of tumor cell diameter and
nuclear volume fraction (nu) on high b diffusion contrast. RESULTS: Results
indicate that clinical pulsed-gradient spin-echo diffusion-weighted signals
measured at high b (~4000 s/mm(2)), long diffusion time (Delta ~40-60 ms), and
long echo time (TE ~60-140 ms) are generally insensitive to tumor cell diameter,
but increase exponentially with nu. Moreover, these results are predicted by a
simple analytic expression for the intracellular restricted water signal with
elevated T2 for the intranuclear versus cytosolic compartment. CONCLUSION:
Nuclear volume fraction is an important characteristic of cancer cells that
modulates the apparent restriction of water at high b on clinical scanners. This
model offers a possible explanation for the apparent unreliable correlation
between tumor cell density (cellularity) and traditional ADC.
PMID- 24357183
TI - Respiratory dysfunction is common in patients with achalasia and improves after
pneumatic dilation.
AB - BACKGROUND: Dysphagia, regurgitation, and chest pain are common achalasia, with a
variable report of pulmonary symptoms possibly due to micro-aspiration. Pneumatic
dilation (PD) may improve pulmonary function. Data on pulmonary dysfunction among
achalasia patients are scanty, and the effect of PD is unknown. AIM: To evaluate
pulmonary dysfunction in patients with achalasia based on clinical and radiologic
evaluation and spirometry and to study the effect of PD at 1-month follow-up.
METHODS: Patients with achalasia (diagnosed using high-resolution manometry and
the Chicago classification) were evaluated prospectively by spirometry before (n
= 38) and 1 month after PD (n = 31). All patients received a chest X-ray, and
patients with respiratory abnormality before PD received high-resolution computed
tomography of the thorax. RESULTS: Of the 38 patients, 17 and 21 had type I and
II achalasia, respectively. The respiratory symptoms, such as pharyngeal symptoms
[27/38 (71 %) vs. 8/31 (26 %); P = 0.0001], cough [23/38 (60.5 %) vs. 5/31 (16
%), P = 0.0001], and dyspnea [8/38 (21 %) vs. 0/31 (0 %), P = 0.006], improved
after treatment with PD. Spirometry showed abnormalities in 17/38 (45 %) patients
before and in 8/15 (53 %) after PD. Median FEV(1), FVC, PEFR, and percentage of
predicted MEF(25-75), improved from 78 % (36-85), 74 % (48-100), 62 % (18-72),
and 48 % (15-66) before to 83 % (58-94), 86 % (55-99), 69 % (38-81), and 59 % (33
78) after PD, respectively (P < 0.05 for all). CONCLUSION: Respiratory symptoms
and spirometry abnormalities are common in patients with achalasia and improved
after successful PD.
PMID- 24357184
TI - Cyclooxygenase-2 and inflammation mediators have a crucial role in reflux-related
esophageal histological changes and Barrett's esophagus.
AB - BACKGROUND: Gastroesophageal reflux (GER) causes injury of the esophageal
squamous epithelium, a condition called reflux esophagitis. The sequence reflux
esophagitis-intestinal metaplasia-dysplasia-invasive cancer is widely accepted as
the main adenocarcinogenetic pathway in the esophagus; however, the mechanisms of
this progression need to be better defined. AIMS: We evaluated COX-2 expression
and activity in biopsies from patients affected with GER, and these parameters
have been correlated with the stage of the disease, ceramide expression,
apoptotic process, and angiogenesis. The effects of celecoxib on bile acid- and
EGF-induced mucosal proliferation, apoptosis and angiogenesis have been also
investigated. METHODS: Four groups of patients were distinguished: non
esophagitis, non erosive esophagitis, erosive esophagitis, and Barrett's
esophagus. COX-2 expression, basal PGE2 levels, proliferative activity, VEGF
expression and apoptosis were evaluated in esophageal biopsies. RESULTS: COX-2
expression, basal PGE2 levels, proliferative activity, VEGF expression and
apoptosis progressively increase from non esophagitis patients to patients with
non erosive and erosive esophagitis, to those with BE. Incubation of the cells
with DCA/EGF increases PGE2 production, proliferative activity and VEGF
production, effects prevented by celecoxib pretreatment. Ceramide expression
increased from non esophagitis patients to patients with non erosive and erosive
esophagitis, and decreased in BE; caspase-3 activity progressively decreased from
non esophagitis to BE patients, suggesting an impairment of the apoptotic process
with disease progression. CONCLUSION: These results stand for a close
relationship between progression of initial steps of gastroesophageal reflux
disease (GERD) and COX-2, proliferative activity and EGF/VEGF expression and
could have implications in GERD treatment in order to prevent its neoplastic
evolution.
PMID- 24357185
TI - A diagnostic approach to patients with suspected lactose malabsorption.
AB - BACKGROUND: The lactose breath test (LBT) is the standard technique for diagnosis
of lactose malabsorption. However, it is time-consuming, strenuous for the
patient and has been reported to have low sensitivity. The lactose intolerance
quick test (LIQT) measures lactase activity in duodenal biopsies and may be
performed as part of upper gastrointestinal endoscopy. AIM: The purpose of this
study was to assess the role of the LBT and LIQT in the case management of
suspected lactose malabsorption. METHODS: The study group included 69 consecutive
patients evaluated by the LBT followed by the LIQT. The test results were
compared, and the sensitivity, specificity, and predictive values of the LBT were
calculated. RESULTS: Mean age of the patients was 54.4 years, male/female ratio
was 1:3, and mean body mass index was 25.2. None had celiac disease on duodenal
biopsy. The LIQT was positive for hypolactasia in 55 patients (80 %): mild in 14
(25 %) and severe in 41 (75 %); 10 (18 %) were symptomatic during the LBT. The
LBT was positive for lactose malabsorption in 32 patients (46 %). Of the 37
patients with normal findings on the LBT, 24 (65 %) had positive findings on the
LIQT: 11 (30 %) mild hypolactasia, 13 (35 %) severe hypolactasia. In one case,
the LBT was positive and the LIQT was negative. The LBT had a sensitivity of 56
%, specificity 93 %, positive predictive value 97 %, and negative predictive
value 35 %. CONCLUSIONS: The LBT may serve as a diagnostic screening tool for
lactose malabsorption. Symptomatic patients with negative LBT results should be
referred for second-line testing with the LIQT.
PMID- 24357186
TI - Molecular evolution of genetic susceptibility to hepatocellular carcinoma.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cancer-related cause of
death worldwide. There are widespread global differences in HCC risk. Although
the impact of geographic prevalence of specific causes of chronic liver disease
on HCC is recognized, the contribution of the underlying genetic architecture to
the risk of HCC remains undefined. Our aim was to characterize evolutionary
trends in genetic susceptibility to HCC. METHODS: We examined the genetic risk
associated with HCC risk alleles identified from genome-wide association studies
and correlated these with geographic location and temporal and spatial patterns
of human migration. RESULTS: A moderate increase in differentiation was noted for
rs2596542 (F st = 0.106) and rs17401966 (F st = 0.116), single nucleotide
polymorphisms (SNPs) associated with an increased risk of HCC in patients with
chronic HCV and HBV, respectively. Both of these SNPs show a recent increase in
allelic frequency with the most recent human migrations into East Asia, Oceania
and the Americas. In contrast another SNP associated with an increased risk of
HCC, rs9275572, showed a lack of differentiation (F st = 0.09) with stable
allelic expression across populations. The genetic risk score for HCC, based on
the allelic frequency and risk odds ratio of five SNPs associated with increased
risk of HCC, was greatest in populations from Africa and decreased with
subsequent migration into Europe and Asia. However, a major increase was noted
with the most recent migrations into Oceania and the Americas. CONCLUSIONS: There
are differences in directional differentiation of HCC risk alleles across human
populations that can contribute to population-based differences in HCC
prevalence.
PMID- 24357187
TI - Low prevalence of microsatellite instability in interval gastric cancers.
AB - BACKGROUND AND AIM: Esophagogastroduodenoscopy (EGD) is recommended at 2-year
intervals in countries with a high prevalence of gastric cancer. The aim of this
study was to determine whether interval gastric cancers that develop within 2
years of a previous complete screening are associated with microsatellite
instability (MSI). METHODS: Newly diagnosed gastric cancer patients who had
undergone gastrectomy were included. Of these 459 patients, 177 were classified
as interval gastric cancer since they were diagnosed within 2 years of a previous
EGD. Noninterval gastric cancer patients were subclassified into 65 patients who
underwent previous EGD between the past 2 and 10 years and 217 patients without
EGD during the last 10 years. Analysis for MSI was conducted using two
mononucleotide and three dinucleotide markers. RESULTS: MSI was found more
frequently in noninterval gastric cancers than in interval gastric cancers (p =
0.009). Interval gastric cancers were associated with a higher prevalence of
early gastric cancer (p = 0.006), smaller size (p < 0.001), and lower TNM stages
(p = 0.006). On logistic regression analysis, noninterval gastric cancers were
related to MSI (p = 0.010) and larger size (>=4 cm) (p = 0.009). Subjects with
interval gastric cancer showed better survival than those with noninterval
gastric cancer (p = 0.006). CONCLUSIONS: During a 2-year screening interval,
noninterval gastric cancers tend to be larger, more advanced, and associated with
MSI. Biannual EGD screening is effective for detecting small gastric cancers at
an early stage, but is not useful in detecting gastric cancers with MSI.
PMID- 24357188
TI - Gastric sarcoidosis in the setting of chronic lymphocytic leukemia.
PMID- 24357189
TI - Symptomatic C2-3 instability in an elderly man with a longstanding atlantoaxial
immobility.
PMID- 24357190
TI - Osteosarcoma of the pelvis treated successfully with repetitive intra-arterial
chemotherapy and radiation therapy: a report of a case with a 21-year follow-up.
PMID- 24357191
TI - A retropharyngeal mass in a young boy.
PMID- 24357193
TI - Bone dust and diced cartilage combined with blood glue: a practical technique for
dorsum enhancement.
AB - The combination of dorsal nasal reconstruction and camouflage of surface
irregularities is an important step in rhinoplasty. We hereby present our
technique of delivering diced cartilage in combination with bone dust to the
nasal dorsum using the patient's blood as a carrier. We advocate use of an
autologous material (blood) as a scaffold for graft delivery, dismissing the use
of a foreign material or fascial wrapping of the graft. Using the patient's blood
for this purpose not only stabilizes the graft into a malleable structure that is
easily applicable to the nasal dorsum, it also decreases the potential for
reaction against foreign material. LEVEL OF EVIDENCE V: This journal requires
that authors assign a level of evidence to each article. For a full description
of these Evidence-Based Medicine ratings, please refer to the Table of Contents
or the online Instructions to Authors www.springer.com/00266 .
PMID- 24357192
TI - Synthesis of new 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones under catalyst
free and solvent-free conditions.
AB - Several new 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones were synthesized via
the three-component condensation reaction of aldehydes, aromatic amines, and
ethyl pyruvate under catalyst-free and solvent-free conditions. Also, 5-(4
hydroxyl-3-nitrophenyl)-1-(4-methoxy-phenyl)-3-(4-methoxyphenylamino)-1,5-dihydro
pyrrol-2-one was synthesized using oxime instead of aldehyde. The eco-friendly,
simple procedure, green procedure, catalyst-free and solvent-free conditions,
short reaction times, and high yields of the products are the advantages of this
method.
PMID- 24357194
TI - Are grafts necessary in rhinoplasty? Cartilage flaps with cartilage-saving
rhinoplasty concept.
AB - BACKGROUND: Cartilage grafts are used routinely in rhinoplasty, but are they
necessary? Can we support the normal anatomy by preserving and transposing the
adjacent tissues? In this study we hypothesize that during rhinoplasty, cartilage
flaps can give adequate support and may decrease the need for cartilage grafts.
METHODS: Included in this study were 147 patients who underwent an open
rhinoplasty technique under general anesthesia between January 2010 and May 2012.
Mean operative time was 73 min (range=44-120 min). After dissection and
septoplasty (if needed), we performed dorsal bone and septal reductions.
Following reduction, upper lateral cartilage superior segments were preserved and
turned inward as cartilage flaps to replace the spreader grafts. Lower lateral
cartilage cranial parts were not excised and were slid over the caudal part to
replace the alar strut grafts. Cartilage from the caudal nasal septum was not
excised; instead, lower lateral cartilages were cephaloposteriorly displaced with
a tongue-in-groove technique to support the nasal tip. RESULTS: Mean follow-up
time was 19.6 months (6-30 months). All patients but 12 were satisfied or
completely satisfied with the results. Among the 12 unsatisfied patients, four
complained of a one-sided inverted-V deformity (secondary spreader grafts were
added), three had supratip deformity (secondary additional dorsal septal
excisions), two demanded extra tip definition (secondary tipoplasty), two were
unhappy with the bone symmetry (secondary osteotomies), and one complained of
hanging columella (secondary excision from the caudal septum). CONCLUSIONS:
Cartilage flaps have some advantages over cartilage grafts. First, graft harvest
is not needed in the former; second, because flaps are a part of the normal
anatomy, they provide a good tissue match, making fixation easier. However, the
tongue-in-groove technique cannot be used in patients who do not need caudal
excision, and cartilage flaps can be inadequate in some patients who may need
additional grafts. EBM LEVEL IV: This journal requires that authors assign a
level of evidence to each article. For a full description of these Evidence-Based
Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 24357197
TI - Utilization of focused antenatal care in Zambia: examining individual- and
community-level factors using a multilevel analysis.
AB - OBJECTIVES: We examine the individual- and community-level factors associated
with the utilization of antenatal care, following the adoption of the focused
antenatal care (FANC) approach in Zambia. METHODS: Using the 2007 Zambia
Demographic and Health Survey, linked with administrative and health facility
census data, we specify two multilevel logistic models to assess the factors
associated with (1) the inadequate use of antenatal care (ANC) (defined as three
or fewer visits) and (2) the non-use of ANC in the first trimester of pregnancy.
RESULTS: Although all women in the selected sample had at least one ANC visit,
40% did not have the minimum number required (four), whereas more than 80% of the
initial check-ups did not occur in the first trimester. At the individual level,
the woman's employment status, quality of ANC received and the husband's
educational attainment are negatively associated, while parity, the household
childcare burden and wealth are positively associated with inadequate utilization
of ANC. Both individual- and community-level characteristics influence inadequate
use and non-use of ANC in the first trimester; however, community-level factors
are relatively stronger in rural areas. CONCLUSION: The results suggest that
improving the content of care during ANC visits may foster adequate use of ANC
and encourage early initiation of ANC visits. Furthermore, health promotion
programmes need to further encourage male involvement in pregnant women's
decision to seek ANC to encourage adequate use of services.
PMID- 24357196
TI - A description of spina bifida cases and co-occurring malformations, 1976-2011.
AB - Mandatory folic acid fortification in the United States corresponded with a
decline in the prevalence of spina bifida (SB). The aim of this study was to
describe the epidemiologic characteristics of isolated versus non-isolated SB
cases in both pre- and post-fortification periods. SB cases in the Slone
Epidemiology Center Birth Defects Study from 1976 to 2011 without chromosomal
anomalies and syndromes were included. A maternal interview, conducted within 6
months of delivery, collected information on demographics, reproductive history,
diet, and supplement use. Daily folic acid intake in the periconceptional period
was calculated using both dietary and supplement information and categorized as
low intake (<400 ug/day) or high intake (>=400 ug/day). SB cases (n = 1170) were
classified as isolated (80.4%) or non-isolated (19.1%). Non-isolated cases were
further divided into subgroups based on accompanying major malformations
(midline, renal, genital, heart, laterality). Compared to non-isolated cases,
isolated cases were more likely to be white, non-Hispanic and have more than 12
years of education. Cases in the renal, genital, and heart subgroups had the
lowest proportions of mothers with a high folic acid intake. The change from pre-
to post-fortification was associated with a decrease in the proportion of
isolated cases from 83% to 72%, though in both periods isolated cases were more
likely to be female and their mothers were more likely to have high folic acid
intake. These findings highlight the importance of separating isolated and non
isolated cases in etiologic research of SB.
PMID- 24357195
TI - The Role of Sdf-1alpha signaling in Xenopus laevis somite morphogenesis.
AB - BACKGROUND: Stromal derived factor-1alpha (sdf-1alpha), a chemoattractant
chemokine, plays a major role in tumor growth, angiogenesis, metastasis, and in
embryogenesis. The sdf-1alpha signaling pathway has also been shown to be
important for somite rotation in zebrafish (Hollway et al., 2007). Given the
known similarities and differences between zebrafish and Xenopus laevis
somitogenesis, we sought to determine whether the role of sdf-1alpha is conserved
in Xenopus laevis. RESULTS: Using a morpholino approach, we demonstrate that
knockdown of sdf-1alpha or its receptor, cxcr4, leads to a significant disruption
in somite rotation and myotome alignment. We further show that depletion of sdf
1alpha or cxcr4 leads to the near absence of beta-dystroglycan and laminin
expression at the intersomitic boundaries. Finally, knockdown of sdf-1alpha
decreases the level of activated RhoA, a small GTPase known to regulate cell
shape and movement. CONCLUSION: Our results show that sdf-1alpha signaling
regulates somite cell migration, rotation, and myotome alignment by directly or
indirectly regulating dystroglycan expression and RhoA activation. These findings
support the conservation of sdf-1alpha signaling in vertebrate somite
morphogenesis; however, the precise mechanism by which this signaling pathway
influences somite morphogenesis is different between the fish and the frog.
PMID- 24357198
TI - Improving Chinese primary care providers' recruitment and retention: a discrete
choice experiment.
AB - INTRODUCTION: Local primary care facilities in China struggle to recruit and
retain doctors and nurses. Implementing policies to address this issue requires
detailed knowledge of the preferences of primary care workers. The aim of this
study is to find out which job attributes affect Chinese primary care providers'
choice of job and whether there are any differences in these job preferences
between doctors and nurses. METHODS: A discrete choice experiment was used to
analyse the job preferences of 517 primary care providers, including 282 doctors
and 235 nurses. RESULTS: Chinese primary care providers in Community Health
Organizations (CHOs) considered monetary factors and non-monetary factors when
choosing a job. Doctors' and nurses' preferences over job attributes were
similar. Though income was important, Chinese primary care providers had
strongest preferences for sufficient welfare benefits, sufficient essential
equipment and respect from the community. Younger primary care providers were
more likely to value training and career development opportunities. CONCLUSION:
In order to retain skilled primary care providers to work in CHOs, policymakers
in China need to improve primary care providers' income, benefits and working
conditions to fulfil their basic needs. Policymakers also need to invest in CHOs'
infrastructure and strengthen training programmes for primary care providers in
order to raise the community's confidence in the services provided by CHOs.
PMID- 24357199
TI - Training to maintain surgical skills during periods of robotic surgery
inactivity.
AB - BACKGROUND: The study was performed to establish a level of practice needed for
newly-trained residents to maintain robotic surgical skills during periods of
robotic inactivity. METHODS: Ten surgical residents were trained to a
standardized level of robotic surgery proficiency with inanimate models. At the
end of two, four and six weeks, the residents practiced with the models for a
total of one hour. Each resident performed a timed tissue closure task
immediately after reaching the proficiency standards and twice in succession at
eight weeks. Time to completion was compared between the three trials with a
repeated measures ANOVA and a post-hoc test. RESULTS: Average time to complete
the tissue closure task decreased by more than 25% over the period between
reaching the proficiency standards and the trials at eight weeks, with the
difference significant (P < 0.004). CONCLUSIONS: Biweekly practice for one hour
was sufficient to maintain robotic surgical skills.
PMID- 24357205
TI - Diabetes management in correctional institutions.
PMID- 24357206
TI - Diabetes and employment.
PMID- 24357207
TI - Third-party reimbursement for diabetes care, self-management education, and
supplies.
PMID- 24357208
TI - Nutrition therapy recommendations for the management of adults with diabetes.
PMID- 24357209
TI - Standards of medical care in diabetes--2014.
PMID- 24357212
TI - Diabetes Care. Introduction.
PMID- 24357213
TI - Summary of revisions to the 2014 Clinical Practice Recommendations.
PMID- 24357210
TI - National standards for diabetes self-management education and support.
PMID- 24357214
TI - Executive summary: Standards of medical care in diabetes--2014.
PMID- 24357215
TI - Diagnosis and classification of diabetes mellitus.
PMID- 24357216
TI - Diabetes care in the school and day care setting.
PMID- 24357217
TI - Diabetes and driving.
PMID- 24357218
TI - Mitoxantrone as a substitute for daunorubicin during induction in newly diagnosed
lymphoblastic leukemia and lymphoma.
AB - BACKGROUND: Daunorubicin, a component of the four-drug induction chemotherapy
regimen for de novo pediatric high-risk acute lymphoblastic leukemia (ALL) and
lymphoblastic lymphoma (LLy), was unavailable in 2011 due to a national drug
shortage. During this time, our institution substituted mitoxantrone 6.25 mg/m(2)
for daunorubicin 25 mg/m(2) on induction Days 1, 8, 15, and 22. While
mitoxantrone has been shown to be effective for relapsed ALL, it has not been
studied in de novo pediatric ALL/LLy. PROCEDURE: We conducted a retrospective
cohort study of newly diagnosed patients with ALL or LLy at our institution
1/2009-4/2013 to compare induction toxicity and response of patients treated with
mitoxantrone versus daunorubicin. RESULTS: Eleven patients received mitoxantrone,
121 patients received daunorubicin. Induction toxicities including deaths,
intensive care unit admissions, fever, bacteremia, and invasive fungal disease
were similar for the two groups. Mean number of days hospitalized during
induction was also similar (mitoxantrone 9.7 days vs. daunorubicin 11.2 days, P =
0.60). Minimal residual disease prevalence at the end of induction was not
significantly different (mitoxantrone 33.3% vs. daunorubicin 23.0%, P = 0.44).
The only significant difference between the groups was that a higher proportion
of patients who received mitoxantrone had consolidation delayed due to
myelosuppression (mitoxantrone 30.0% vs. daunorubicin 6.0%, P = 0.03).
CONCLUSION: Induction toxicity and response for new ALL/LLy patients treated with
mitoxantrone in place of daunorubicin were similar to the toxicity and response
seen with conventional daunorubicin. Mitoxantrone is a reasonable replacement for
daunorubicin in times of drug shortage.
PMID- 24357219
TI - A tool to enhance medical care, communication, and patients' understanding of
high-resolution anoscopy.
PMID- 24357220
TI - Prediction model for 30-day hospital readmissions among patients discharged
receiving outpatient parenteral antibiotic therapy.
AB - BACKGROUND: Factors associated with readmission for patients prescribed
outpatient parenteral antibiotic therapy (OPAT) at hospital discharge have not
been definitively identified. The study aim was to develop a model of 30-day
readmissions for OPAT patients. METHODS: A database comprising 782 OPAT patients
treated between 2009 and 2011 at a single academic center was created. Variables
collected included patient demographics, comorbidities, infections, and
antibiotic classes. Final model discrimination was assessed using the c
statistic, and calibration was examined graphically. RESULTS: Mean patient age
was 58 years (range, 18-95 years), 43% were women, and the most common diagnoses
were bacteremia (24%), osteomyelitis (20%), and pyelonephritis (13%). The
unplanned 30-day readmission rate was 26%. The leading indications for
readmission were non-infection related (30%), worsening infection (29%), and new
infection (19%). The final regression model consisted of age (odds ratio [OR],
1.09 per decade; 95% confidence interval [CI], 0.99-1.21), aminoglycoside use
(OR, 2.33; 95% CI, 1.17-4.57), resistant organisms (OR, 1.57; 95% CI, 1.03-2.36),
and number of prior hospital discharges without intravenous antibiotics in the
past 12 months (OR, 1.20 per prior admission; 95% CI, 1.09-1.32). The c-statistic
was 0.61 and the highest-risk quintile of patients had almost a 3-fold higher
rate of readmission compared to the lowest. CONCLUSIONS: Patients prescribed OPAT
are at risk for readmission. A subgroup of patients at especially high risk can
be identified using easily obtainable clinical characteristics at the time of
hospital discharge. More intensive interventions to prevent OPAT readmissions
should be targeted and tested with those at highest risk.
PMID- 24357221
TI - Exposure of neonatal rats to maternal cafeteria feeding during suckling alters
hepatic gene expression and DNA methylation in the insulin signalling pathway.
AB - Nutrition in early life is a determinant of lifelong physiological and metabolic
function. Diseases that are associated with ageing may, therefore, have their
antecedents in maternal nutrition during pregnancy and lactation. Rat mothers
were fed either a standard laboratory chow diet (C) or a cafeteria diet (O) based
upon a varied panel of highly palatable human foods, during lactation. Their
offspring were then weaned onto chow or cafeteria diet giving four groups of
animals (CC, CO, OC, OO n = 9-10). Livers were harvested 10 weeks post-weaning
for assessment of gene and protein expression, and DNA methylation. Cafeteria
feeding post-weaning impaired glucose tolerance and was associated with sex
specific altered mRNA expression of peroxisome proliferator activated receptor
gamma and components of the insulin signalling pathway (Irs2, Akt1 and IrB).
Exposure to the cafeteria diet during the suckling period modified the later
response to the dietary challenge. Post-weaning cafeteria feeding only down
regulated IrB when associated with cafeteria feeding during suckling (group OO,
interaction of diet in weaning and lactation P = 0.041). Responses to cafeteria
diet during both phases of the experiment varied between males and females.
Global DNA methylation was altered in the liver following cafeteria feeding in
the post-weaning period, in males but not females. Methylation of the IrB
promoter was increased in group OC, but not OO (P = 0.036). The findings of this
study add to a growing evidence base that suggests tissue function across the
lifespan a product of cumulative modifications to the epigenome and
transcriptome, which may be both tissue and sex-specific.
PMID- 24357222
TI - Efficacy of single-pill perindopril/indapamide in patients with hypertension and
type 2 diabetes.
AB - OBJECTIVE: Hypertension and type 2 diabetes in combination are associated with a
significantly higher level of cardiovascular events. The aim of this prospective
study was to evaluate the antihypertensive efficacy and tolerability of single
pill perindopril/indapamide in patients with hypertension and type 2 diabetes.
DESIGN AND METHODS: Patients with both hypertension and type 2 diabetes were
enrolled in this multicenter, prospective, open clinical study. Single-pill
perindopril/indapamide was either prescribed on its own (started or switched to
from previous treatment) or added to previous therapy. Perindopril/indapamide
dosage could be increased, from 5/1.25 mg to 10/2.5 mg once daily, if blood
pressure (BP) was uncontrolled. BP and tolerability were assessed at 4 visits
over a 6-month period. Microalbuminuria was assessed at baseline and 6 months in
a subgroup. RESULTS: 397 patients were analyzed (age 57.6 +/- 9.4 years, men 46
%). At baseline, systolic blood pressure (SBP) was 160.0 +/- 14.3 mmHg, diastolic
blood pressure (DBP) 95.2 +/- 8.3 mmHg, and pulse pressure 64.8 +/- 12.7 mmHg.
Nearly half (45 %) of patients received perindopril/indapamide alone and 55 %
added this single-pill combination to existing therapy. After 6 months, SBP fell
by 30 mmHg, DBP by 14 mmHg, and pulse pressure by 16 mmHg (all p < 0.0001). SBP
was normalized (<140 mmHg) in 84 % of patients who took perindopril/indapamide
5/1.25 mg alone and in 90 % of patients who took perindopril/indapamide 10/2.5 mg
alone. Tolerability was rated "good" or "better" by nearly all (99 %) patients.
In a microalbuminuria subgroup (n = 59; baseline microalbuminuria 20-200 mg/L;
average age 60.5 +/- 11.5 years; 28 men [47 %]), there was a significant decrease
in SBP (from 160.5 +/- 13.9 mmHg to 132.6 +/- 12.0 mmHg) and DBP (from 95.3 +/-
7.8 mmHg to 81.6 +/- 8.4 mmHg) (p < 0.001). Target SBP was reached by 71 % of
these patients. Microalbuminuria decreased in 75 % of the subgroup during the
follow-up period; levels fell significantly from 45 mg/L (30-88 mg/L) to 30 mg/L
(20-50 mg/L) (p < 0.0001). CONCLUSION: Treatment with single-pill
perindopril/indapamide 5/1.25 or 10/2.5 mg significantly reduced BP, improved BP
control, and enhanced kidney protection in patients with hypertension and type 2
diabetes in everyday clinical practice.
PMID- 24357223
TI - Life-long physical activity restores metabolic and cardiovascular function in
type 2 diabetes.
AB - PURPOSE: Short-to-moderate duration exercise training improves fitness and lowers
cardiovascular risk in type 2 diabetes (T2DM). However, the impact of long-term
compliance to an active lifestyle of T2DM patients on cardiovascular risk factors
has never been studied but could provide information on the maximal achievable
health effect of physical activity in T2DM. This study examined the impact of a
life-long active lifestyle by comparing physical fitness, cardiovascular risk and
vascular function between long-term physically active T2DM patients versus
sedentary T2DM patients and controls. METHODS: Fitness, HOMA-IR, brachial artery
flow-mediated dilation (FMD) and lifetime risk for cardiovascular disease were
assessed in 15 exercising T2DM patients, 12 age-, sex- and weight-matched
sedentary T2DM patients and 9 sedentary men free of established cardiovascular
and metabolic disease as controls. Long-term regular exercise was defined as self
reported participation of >2.5 h of (predominantly) endurance exercise per week,
which was performed for 18-47 years. RESULTS: Sedentary T2DM patients showed
lower fitness (21.8 +/- 2.3, 32.6 +/- 6.0 and 31.1 +/- 3.2 ml O2/kg/min), higher
HOMA-IR (8.3 +/- 5.0, 2.0 +/- 1.8 and 1.1 +/- 0.5 100/%S) and higher lifetime
risk scores (17.3 +/- 5.4, 9.3 +/- 5.0 and 8.9 +/- 3.9 %) compared to active
peers and controls, respectively. Brachial artery FMD was lower in sedentary T2DM
patients compared with active peers, but not in controls (3.3 +/- 1.2, 5.2 +/-
2.1 and 3.8 +/- 1.2%). CONCLUSIONS: Life-long active T2DM patients have superior
fitness levels, HOMA-IR, cardiovascular risk and FMD compared to sedentary peers,
whilst no differences were found when compared to controls. This study provides
evidence that a life-long active lifestyle, even in T2DM, may be able to
effectively normalize cardiovascular risk.
PMID- 24357224
TI - Blunted cutaneous vasoconstriction and increased frequency of presyncope during
an orthostatic challenge under moderate heat stress in the morning.
AB - PURPOSE: In normothermia, the tolerance time to presyncope during an orthostatic
challenge is shortened during the early morning. Heat stress reduces tolerance to
presyncope and the degree of cutaneous vasoconstriction prior to presyncope.
However, whether these changes show diurnal variations remains unknown.
Therefore, we examined diurnal changes in orthostatic tolerance and cutaneous
vascular conductance (CVC) during an orthostatic challenge under moderate heat
stress. METHODS: Each lower body negative pressure (LBNP) under normothermia and
whole body heat stress was applied for 7 min or until the appearance of
presyncopal symptoms in 16 males at both 08:00 (a.m.) and 17:00 hours (p.m.).
Measurements included internal and skin temperatures, forearm skin blood flow,
arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean
arterial pressure, normalized to CVC prior to LBNP and expressed as %CVC.
RESULTS: The average tolerance time in eight subjects exhibiting presyncopal
symptoms due to LBNP and moderate heat stress was significantly shorter in the
a.m. than in the p.m. (3.7 +/- 0.8 versus 6.7 +/- 0.3 min, respectively; P =
0.005). Neither %CVC during LBNP in these subjects under moderate heat stress nor
normothermia were significantly decreased in the a.m. (P > 0.05, respectively).
CONCLUSIONS: These findings indicate an orthostatic challenge even during
moderate heat stress that led to an increase in the frequency of presyncope,
especially in the morning. The reduction in tolerance was accompanied by blunted
cutaneous vasoconstriction prior to presyncope. Hence, diurnal changes in
cutaneous vascular responses during combined orthostatic and heat stresses should
contribute, at least partly, to heat-induced orthostatic intolerance in the
morning.
PMID- 24357225
TI - Engineering the oxyanion hole of trypsin for promoting the reverse of
proteolysis.
AB - Although proteases are capable of synthesizing peptide bonds via the reverse of
proteolysis, they are not proficient at peptide fragment ligation. Further
manipulations are needed to shift the native enzyme activity from the cleavage to
the synthesis of peptides especially when longer peptides or even proteins are
the target molecules of the reaction. This account reports on the synthetic
potential of trypsin variants with engineered oxyanion holes mutated by proline
mutations, which were designed to minimize proteolytic side reactions during
peptide bond synthesis. From the six single and double proline-mutated trypsins,
in particular, trypsinQ192P came out as the most promising biocatalyst enabling
not only the ligation of cleavage-sensitive peptide fragments but also the
selective N-terminal modification of a real protein substrate.
PMID- 24357226
TI - Oncology providers' evaluation of the use of an automatically generated cancer
survivorship care plan: longitudinal results from the ROGY Care trial.
AB - PURPOSE: Previous studies have merely investigated oncology providers' a priori
attitudes toward SCPs. The purpose of the current study was to longitudinally
evaluate oncology providers' expectations and actual experiences with the use of
an automatically generated Survivorship Care Plan (SCP) in daily clinical
practice. METHODS: Between April 2011 and October 2012, the participating
oncology providers (i.e., gynecologists, gynecologic oncologists, oncology
nurses) provided usual care or SCP care to 222 endometrial and 85 ovarian cancer
patients included in the Registrationsystem Oncological GYnecology (ROGY) Care
trial. All (n = 43) oncology providers in both arms were requested to complete a
questionnaire before and after patient inclusion regarding their expectations and
evaluation of SCP care. RESULTS: Before patient inclusion, 38 (88%; 21 SCP, 17
usual care), and after patient inclusion, 35 (83%; 20 SCP, 15 usual care)
oncology providers returned the questionnaire. After patient inclusion, oncology
providers were generally satisfied with the SCP (M = 7.1, SD = 1.3, with 1 = not
at all-10 = very much) and motivated to keep using the SCP (M = 7.9, SD = 1.5).
Most providers (64%) encountered barriers. Twenty-five percent felt they used
more time for consultations (M = 7.3 min, SD = 4.6). However, self-reported
consultation time did not differ between before (M = 21.8 min, SD = 11.6) and
after patient inclusion (M = 18.7, SD = 10.6; p = 0.22) or between SCP care (M =
18.5, SD = 10.3) and usual care (M = 22.0, SD = 12.2; p = 0.21). CONCLUSIONS:
Oncology providers using the SCP were generally satisfied and motivated to keep
using the SCP. However, the findings of the current study suggest that even when
the SCP can be generated automatically, oncology providers still have
difficulties with finding the time to discuss the SCP with their patients.
IMPLICATIONS FOR CANCER SURVIVORS: If SCP care is indeed effective, overcoming
the perceived barriers is needed before large-scale implementation in order for
cancer survivors to fully benefit from the potential advantages of SCPs.
PMID- 24357227
TI - Mutations in the Drosophila ortholog of the vertebrate Golgi pH regulator (GPHR)
protein disturb endoplasmic reticulum and Golgi organization and affect systemic
growth.
AB - Sorting of secretory cargo and retrieval of components of the biosynthetic
pathway occur in organelles such as the Golgi apparatus, the endoplasmic
reticulum and the endosomes. In order to perform their functions in protein
sorting, these organelles require a weakly acidified lumen. In vitro data have
shown that Golgi luminal pH is in part regulated by an anion channel called Golgi
pH Regulator (GPHR). Mammalian cells carrying a mutated GPHR version present an
increased luminal pH leading to delayed protein transport, impaired glycosylation
and Golgi disorganization. Using Drosophila as a model system, we present here
the first phenotypic consequences, at the organism level, of a complete lack of
GPHR function. We show that, although all individuals carrying complete loss-of
function mutations in the dGPHR gene can go through embryonic development, most
of them die at late larval stages. The dGPHR mutations are, however, sublethal
and can therefore generate escapers that are smaller than controls. Using
cellular and molecular readouts, we demonstrate that the effects of dGPHR
mutation on larval growth are not due to Insulin signaling pathway impairment and
can be rescued by providing dGPHR in only some of the larval tissues. We reveal
that, although functionally exchangeable, the invertebrate and vertebrate GPHRs
display not completely overlapping sub-cellular localization. Whereas the
mammalian GPHR is a Golgi-only associated protein whose inactivation disturbs the
Golgi apparatus, our data suggest that dGPHR is expressed in both the ER and the
Golgi and that dGPHR mutant flies have defects in both organelles that lead to a
defective secretory pathway.
PMID- 24357228
TI - Mesomere-derived glutamate decarboxylase-expressing blastocoelar mesenchyme cells
of sea urchin larvae.
AB - The ontogenetic origin of blastocoelar glutamate decarboxylase (GAD)-expressing
cells (GADCs) in larvae of the sea urchin Hemicentrotus pulcherrimus was
elucidated. Whole-mount in situ hybridisation (WISH) detected transcription of
the gene that encodes GAD in H. pulcherrimus (Hp-gad) in unfertilised eggs and
all blastomeres in morulae. However, at and after the swimming blastula stage,
the transcript accumulation was particularly prominent in clumps of ectodermal
cells throughout the embryonic surface. During the gastrula stage, the
transcripts also accumulated in the endomesoderm and certain blastocoelar cells.
Consistent with the increasing number of Hp-gad transcribing cells, immunoblot
analysis indicated that the relative abundance of Hp-Gad increased considerably
from the early gastrula stage until the prism stage. The expression pattern of
GADCs determined by immunohistochemistry was identical to the pattern of Hp-gad
transcript accumulation determined using WISH. In early gastrulae, GADCs formed
blastocoelar cell aggregates around the blastopore with primary mesenchyme cells.
The increase in the number of blastocoelar GADCs was inversely proportional to
the number of ectodermal GADCs ranging from a few percent of total GADCs in early
gastrulae to 80% in late prism larvae; this depended on ingression of ectodermal
GADCs into the blastocoel. Some of the blastocoelar GADCs were fluorescein
positive in the larvae that developed from the 16-cell stage chimeric embryos;
these comprised fluorescein-labeled mesomeres and unlabelled macromeres and
micromeres. Our finding indicates that some of the blastocoelar GADCs are derived
from the mesomeres and thus they are the new group of mesenchyme cells, the
tertiary mesenchyme cells.
PMID- 24357230
TI - Cell migration and division in amoeboid-like fission yeast.
AB - Yeast cells are non-motile and are encased in a cell wall that supports high
internal turgor pressure. The cell wall is also essential for cellular
morphogenesis and cell division. Here, we report unexpected morphogenetic changes
in a Schizosaccharomyces pombe mutant defective in cell wall biogenesis. These
cells form dynamic cytoplasmic protrusions caused by internal turgor pressure and
also exhibit amoeboid-like cell migration resulting from repeated protrusive
cycles. The cytokinetic ring responsible for cell division in wild-type yeast
often fails in these cells; however, they were still able to divide using a ring
independent alternative mechanism relying on extrusion of the cell body through a
hole in the cell wall. This mechanism of cell division may resemble an ancestral
mode of division in the absence of cytokinetic machinery. Our findings highlight
how a single gene change can lead to the emergence of different modes of cell
growth, migration and division.
PMID- 24357229
TI - Insulin signaling regulates neurite growth during metamorphic neuronal
remodeling.
AB - Although the growth capacity of mature neurons is often limited, some neurons can
shift through largely unknown mechanisms from stable maintenance growth to
dynamic, organizational growth (e.g. to repair injury, or during development
transitions). During insect metamorphosis, many terminally differentiated larval
neurons undergo extensive remodeling, involving elimination of larval neurites
and outgrowth and elaboration of adult-specific projections. Here, we show in the
fruit fly, Drosophila melanogaster (Meigen), that a metamorphosis-specific
increase in insulin signaling promotes neuronal growth and axon branching after
prolonged stability during the larval stages. FOXO, a negative effector in the
insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that
secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon
cell-targeted expression of dominant-negative constructs for other components of
the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K) also partially suppressed
the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast,
expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1,
Rheb, and TOR, as well as RNA interference for negative regulators of insulin
signaling (PTEN, FOXO), stimulated overgrowth. Interestingly, InR displayed
little effect on larval CCAP/bursicon neuron growth, in contrast to its strong
effects during metamorphosis. Manipulations of insulin signaling in many other
peptidergic neurons revealed generalized growth stimulation during metamorphosis,
but not during larval development. These findings reveal a fundamental shift in
growth control mechanisms when mature, differentiated neurons enter a new phase
of organizational growth. Moreover, they highlight strong evolutionarily
conservation of insulin signaling in neuronal growth regulation.
PMID- 24357232
TI - [Hemangioma and vascular malformations in the head and neck region as a prime
example of interdisciplinarity].
PMID- 24357231
TI - Stress granules and Plasmodium liver stage infection.
AB - Organisms have evolved numerous strategies to control infection by an array of
intracellular pathogens. One cell autonomous pathogen control strategy is global
inhibition of protein synthesis via stress granule (SG) formation. SGs are
induced by stressful stimuli such as oxidative stress and nutrient deprivation,
and are known to counteract both viral and bacterial infections. Pathogens, in
turn, may actively block an infected cell's ability to form SGs. In vitro and in
vivo, many liver stage malaria parasites are eliminated during development. We
show here that SG formation is not amongst the strategies used for elimination of
parasites from hepatocytes. Neither cell traversal, sporozoite invasion, nor
rapid parasite growth leads to the formation of SGs. Furthermore, Plasmodium
berghei infection does not compromise the ability of infected cells to assemble
SGs in response to oxidative or nutritional stress. Plasmodium infection is
therefore not detected by hepatocytes as a strong stressor necessitating global
translational repression in response, highlighting the idea that Plasmodium has
evolved strategies to ensure its remarkable growth in the hepatocyte while
maintaining host cell homeostasis.
PMID- 24357233
TI - [Potential and limitations of modern embolization therapy].
AB - Correct clinical and angiographic classification of vascular anomalies, including
consideration of their flow pattern (high-flow versus low-flow), is the basis of
accurate indications for minimally invasive therapy modalities such as
embolization. Technical advancements and miniaturization of catheter materials
(including steerable microwires, flow-directed microcatheters and detachable
tips) gained access for embolotherapy to lesions anywhere in the body. The aim of
embolization, which is mainly indicated for therapy of high-flow arteriovenous
malformations, is the complete, permanent occlusion of the lesion nidus.
Nowadays, embolotherapy is performed using permanent liquid embolization agents,
in multiple staged sessions. This technique reduces complications such as
ischemic necrosis and peripheral nerve lesions compared to alcohol embolization.
Sole occlusion of the arterial inflow by surgical resection or interventional
coil application is considered obsolete. The size of the lesion and the high
treatment costs limit the use of embolotherapy.
PMID- 24357234
TI - [Potential and limitations of dye laser therapy for capillary malformations].
AB - Capillary malformations (port-wine stains) are observed in less than 1 % of
neonates and may occur coincidentally with other vascular and nonvascular
malformations. Two thirds of lesions occur in the head and neck area and may have
important cosmetic and psychological implications for the patients. Treatment
with flashlamp-pumped pulsed dye lasers is still the therapy of choice for
capillary malformations and can be applied to infants. If the laser device is
used appropriately, the rate of persistent side effects is low. Although laser
treatment achieves good clearance in the majority of patients with capillary
malformations, complete clearance is rare. New therapeutic options are thus
urgently required.
PMID- 24357235
TI - Selective synthesis of indazoles and indoles via triazene-alkyne cyclization
switched by different metals.
AB - We described two orthogonal heterocycle syntheses, where an arene bearing both an
alkyne and a triazene functionality underwent two distinct cyclization pathways
mediated by different transition metals. Starting from the same substrates, a
synthesis of 2H-indazole was accomplished by a Cu(II) salt promoted oxidative
cyclization, while 2-substituted indoles could be accessed via a Ag(I) salt
mediated N-N bond cleavage. This method represents the first synthesis of indoles
from alkynyl triazenes. Computational analysis was performed for both reaction
pathways, supporting a Lewis acid role for Cu and a pi-acid catalysis for Ag.
PMID- 24357236
TI - Impacts of bioremediation schemes for the mitigation of a low-dose anthracene
contamination on free-living marine benthic nematodes.
AB - A microcosm experiment was used to examine (1) the effects of different
bioremediation schemes on degradation of anthracene and the structure of free
living marine nematodes in a lightly contaminated (4.5 MUg g(-1)) sediment from
Bizerte lagoon and (2) the responses of the nematode community upon an artificial
spiking of a low dose anthracene (1 MUg g(-1)). For that purpose sediment
microcosms were incubated in laboratory for 40 days. Bioremediation techniques
decreased the anthracene contamination, and interestingly, biodegradation were
more efficient when anthracene was artificial supplied into the sediment
suggesting that the addition of bioavailable anthracene stimulated the bacterial
community to adjust towards a PAH-degrading community. Spiking with this low dose
of anthracene provoked significant changes in the nematode community structure
and abundance, with the elimination of specific species such as Mesacanthion
diplechma, the decrease of the dominant species Oncholaimus campylocercoides and
the increase in abundance of opportunistic species such as Spirinia parasitifera.
This would suggest a low tolerance of the nematode community despite the presence
of a weak anthracene contamination in the sediment that could have allow
dominance of an anthracene tolerant nematode species. Anthracene toxicity was
alleviated in biostimulation treatments, leading to a strong increase in nematode
abundance, concomitantly with changes in the nematode community structure;
Prochromadorella neapolitana became the most abundant species.
PMID- 24357237
TI - Rapid adaptation of some phytoplankton species to osmium as a result of
spontaneous mutations.
AB - To understand the vulnerability of individual species to anthropogenic
contamination, it is important to evaluate the different abilities of
phytoplankton to respond to environmental changes induced by pollution. The
ability of a species to adapt, rather than its initial tolerance, is the basis
for survival under rapidly increasing levels of anthropogenic contamination. High
doses of osmium (Os) cause massive destruction of diverse phytoplankton groups.
In this study, we found that the coastal chlorophyte Tetraselmis suecica and the
continental chlorophyte Dictyosphaerium chlorelloides were able to adapt to a
lethal dose of Os. In these species, Os-resistant cells arose as a result of rare
spontaneous mutations (at rates of approximately 10(-6) mutants per cell
division) that occurred before exposure to Os. The mutants remained in the
microalgal populations by means of mutation-selection balance. The huge size of
phytoplankton populations ensures that there are always enough Os-resistant
mutants to guarantee the survival of the population under Os pollution. In
contrast, we observed that neither a haptophyte species from open ocean regions
nor a cyanobacterium from continental freshwater were able to adapt to the lethal
Os dose. Adaptation of phytoplankton to Os contamination is relevant because
industrial activities are leading to a rapid increase in Os pollution worldwide.
PMID- 24357238
TI - Laparoscopic inguinal hernioplasty after radical prostatectomy: is it safe?
Prospective clinical trial.
AB - INTRODUCTION: Despite inguinal hernia repair being one of the most common
elective operations performed in general surgical practice, there are many
controversies including indications for repair and selection of the surgical
technique. In recent years, laparoscopic repair has gained wider acceptance
because it is associated with fewer postoperative complications and less chronic
pain when compared with conventional approaches with similar recurrence rate.
However, patients with lower abdominal surgery are contraindicated for
laparoscopic approach. There are few studies that evaluated whether patients who
have been subjected to radical prostatectomy might be subjected to laparoscopic
hernia repair with the same benefits as those without previous radical
prostatectomy. METHODS: Between March 2010 and March 2013, 20 consecutive
patients, who had been subjected to prior radical prostatectomy, underwent
laparoscopic transabdominal inguinal repair and were followed prospectively.
Surgical procedure was performed using a standard technique. RESULTS: Mean
operative time was 67.5 min. There was only one (5%) intraoperative minor
complication, an injury to the inferior epigastric vessels, which was managed by
clipping of the vessels. There were no major postoperative complications. After
24 h and on the seventh postoperative day, 85 and 90% of patients had no pain or
only complained of discomfort, respectively. Nine patients (45%) did not need any
analgesics postoperatively. The mean time to return to leisure activities and to
work was 3.1 and 5.6 days, respectively. There was no conversion to open surgery.
All patients were discharged within 24 h. After a mean follow-up of 14 months,
none of the patients presented recurrence. CONCLUSION: TAPP after prostatectomy
is safe and effective. It seems that patients undergoing laparoscopic repair
after radical prostatic resection have the same benefits as those without
prostatectomy.
PMID- 24357239
TI - Proteome analysis of roots of wheat seedlings under aluminum stress.
AB - The root apex is considered the first sites of aluminum (Al) toxicity and the
reduction in root biomass leads to poor uptake of water and nutrients. Aluminum
is considered the most limiting factor for plant productivity in acidic soils.
Aluminum is a light metal that makes up 7 % of the earth's scab dissolving ionic
forms. The inhibition of root growth is recognized as the primary effect of Al
toxicity. Seeds of wheat cv. Keumkang were germinated on petridish for 5 days and
then transferred hydroponic apparatus which was treated without or with 100 and
150 MUM AlCl3 for 5 days. The length of roots, shoots and fresh weight of wheat
seedlings were decreased under aluminum stress. The concentration of K(+), Mg(2+)
and Ca(2+) were decreased, whereas Al(3+) and P2O5 (-) concentration was
increased under aluminum stress. Using confocal microscopy, the fluorescence
intensity of aluminum increased with morin staining. A proteome analysis was
performed to identify proteins, which are responsible to aluminum stress in wheat
roots. Proteins were extracted from roots and separated by 2-DE. A total of 47
protein spots were changed under Al stress. Nineteen proteins were significantly
increased such as sadenosylmethionine, oxalate oxidase, malate dehydrogenase,
cysteine synthase, ascorbate peroxidase and/or, 28 protein spots were
significantly decreased such as heat shock protein 70, O-methytransferase 4,
enolase, and amylogenin. Our results highlight the importance and identification
of stress and defense responsive proteins with morphological and physiological
state under Al stress.
PMID- 24357240
TI - Human whole-blood (1)H2O longitudinal relaxation with normal and high-relaxivity
contrast reagents: influence of trans-cell-membrane water exchange.
AB - PURPOSE: Accurate characterization of contrast reagent (CR) longitudinal
relaxivity in whole blood is required to predict arterial signal intensity in
contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal
relaxation rate constants (R1 ) over a concentration range for non-protein
binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0
Tesla (T) under physiologic arterial conditions. METHODS: Relaxivities of
gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from
0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be
expected in CE-MRA. RESULTS: In plasma, the (1) H2 O R1 [CR]-dependence was
nonlinear for gadobenate and gadofosveset secondary to CR interactions with the
serum macromolecule albumin, and was well described by an analytical expression
for effective 1:1 binding stoichiometry. In whole blood, the (1) H2 O R1 [CR]
dependence was markedly non-linear for all CRs, and was well-predicted by an
expression for equilibrium exchange of water molecules between plasma and
intracellular spaces using a priori parameter values only. CONCLUSION: In whole
blood, (1) H2 O R1 exhibits a nonlinear relationship with [CR] over 0 to 18 mM
CR. The nonlinearity is well described by exchange of water between erythrocyte
and plasma compartments, and is particularly evident for high relaxivity CRs.
PMID- 24357241
TI - Bilateral anterior thoracotomy (clamshell incision) is the ideal emergency
thoracotomy incision: an anatomical study: reply.
PMID- 24357242
TI - Management of thoracic esophageal perforation.
AB - BACKGROUND: The aim of this study was to characterize an optimal strategy in
managing thoracic esophageal perforation, focusing on the differential diagnosis
and treatment of patients with contained versus noncontained perforations and on
the importance of the time interval between injury and repair and how that
affects the outcome of a primary repair. METHODS: A retrospective study was
conducted. A strict definition of contained or noncontained perforation was based
on a combination of esophagography, chest CT scan, and endoscopy as well as
monitoring systemic symptoms. Management options for our cohort included
conservative therapy, primary repair and debridement, esophagectomy, and mesh
covered stents. Patients were stratified into two groups according to the time
interval after injury: <= 48-h group and >48-h group. RESULTS: Between January
1997 and January 2013, a total of 66 consecutive patients (47 males and 19
females, mean age = 49.1 +/- 16.2 years) were treated for thoracic esophageal
perforation. Perforation was confirmed by esophagography in 51 patients and by
endoscopy in 15 patients. Eighteen patients were assigned to the contained
perforation group. All these patients were successfully cured without surgery.
The noncontained group included 48 patients; its mortality rate was 7.7 % (3/39)
with surgery and 55.6 % (5/9) with stent placement. Compared with the contained
group, the noncontained group had a significantly longer length of stay (LOS) (16
+/- 3.2 vs. 26.3 +/- 18.7 days; p < 0.05) and a higher mortality rate (0 vs. 22.9
%, p < 0.05). In the two time-interval groups, patient characteristics, including
age, gender, and comorbidities, etiologic cause, length and location of the
perforation, and the incidence of using tissue buttress were similar (p > 0.05).
The incidence of postoperative leak was significantly higher in >48-h group (0 in
<= 48-h group vs. 37.5 % in >48-h group; p < 0.01). In addition, the >48-h group
had a significantly longer LOS (18.0 +/- 9.1 days in <= 48-h group vs. 31.5 +/-
18.6 days in >48-h group; p < 0.01). The two deaths occurred in the >48-h group
(0 in <= 48-h group vs. 12.5 % in >48-h group; p > 0.05) due to postoperative
leaks. CONCLUSIONS: Contained or noncontained perforation should be rigorously
differentiated. Then, for a contained perforation, conservative therapy coupled
with repeated imaging is reasonable treatment. For a noncontained perforation, a
primary repair can be safely performed within 48 h after injury. After that, a
primary repair is still reasonable but is associated with an increased risk of
postoperative leaks.
PMID- 24357243
TI - Comparison of two models of surgical care for patients with cleft lip and palate
in resource-challenged settings.
AB - BACKGROUND: The Peruvian health system is limited in providing specialized care
for patients with clefts because there are an insufficient number of hospitals
and few specially trained doctors in rural areas of the country. The most common
model of care in these areas is the surgical mission wherein experienced cleft
surgeons perform surgeries and teach local doctors. The purpose of this research
was to identify the differences in outcome between the surgical mission trip and
the referral center model of care provided by the same team. METHODS: A
retrospective analysis (2002-2012) was performed on data from surgical outcomes
provided by the Outreach Surgical Center Lima that utilized both models of care
(surgical mission and referral center). A total of 935 procedures were performed
in 680 patients with clefts who were treated by the Outreach Surgical Center
Program Lima since 2002. Patients in both groups were identified from our records
(medical records and screening-day registries). All patients underwent a physical
examination, had photographs taken, and any unfavorable results and complications
were documented. Comparison of categorical variables (including outcomes) between
care models was performed using Pearson's chi (2) test or Fisher's exact test
when appropriate. In all cases a two-tailed test was performed and the p value
for rejecting the null hypothesis (no difference or no association) was set at
0.05. RESULTS: We found significant differences between the two models of care
with respect to unilateral cleft lip and cleft palate dehiscence (p = 0.02 and p
= 0.04, respectively), palate postoperative hemorrhage (p < 0.01), and palatal
fistula (p < 0.01) outcomes. DISCUSSION: Differences in observed surgical
outcomes between the two models might be attributed to the surgeon's performance
and/or the patient's age, and these factors are also considered with respect to
the model of care. Limitations in long-term medical evaluation at each site
should be identified and strategies to improve surgical outcomes must be
developed to ensure that patients served by surgical missions obtain the same
results achieved at a referral center.
PMID- 24357244
TI - General and acute care surgical procedures in patients with left ventricular
assist devices.
AB - BACKGROUND: Left ventricular assist devices (LVADs) have become common as a
bridge to heart transplant as well as destination therapy. Acute care surgical
(ACS) problems in this population are prevalent but remain ill-defined.
Therefore, we reviewed our experience with ACS interventions in LVAD patients.
METHODS: A total of 173 patients who received HeartMate((r)) XVE or
HeartMate((r)) II (HMII) LVADs between December 2001 and March 2010 were studied.
Patient demographics, presentation of ACS problem, operative intervention, co
morbidities, transplantation, complications, and survival were analyzed. RESULTS:
A total of 47 (27 %) patients underwent 67 ACS procedures at a median of 38 days
after device implant (interquartile range 15-110), with a peri-operative
mortality rate of 5 % (N = 3). Demographics, device type, and acuity were
comparable between the ACS and non-ACS groups. A total of 21 ACS procedures were
performed emergently, eight were urgent, and 38 were elective. Of 29 urgent and
emergent procedures, 28 were for abdominal pathology. In eight patients, the
cause of the ACS problem was related to LVADs or anticoagulation. Cumulative
survival estimates revealed no survival differences if patients underwent ACS
procedures (p = 0.17). Among HMII patients, transplantation rates were unaffected
by an ACS intervention (p = 0.2). CONCLUSIONS: ACS problems occur frequently in
LVAD patients and are not associated with adverse outcomes in HMII patients. The
acute care surgeon is an integral member of a comprehensive approach to effective
LVAD management.
PMID- 24357246
TI - Trends in incidentally identified thyroid cancers over a decade: a retrospective
analysis of 2,090 surgical patients.
AB - BACKGROUND: The aim of this study was to describe trends in the incidence of
incidental thyroid cancers and compare their characteristics with clinically
presenting cancers. METHODS: We performed a retrospective review of patients with
thyroid cancer who underwent thyroid surgery from 2003 to 2012. Patients' initial
presentation was categorized as incidental (on imaging or final surgical
pathology) or clinical (palpable or symptomatic) cancer. Characteristics of
incidental and clinical cancers were compared. RESULTS: Of the 2,090 patients who
underwent thyroid surgery, 680 (33 %) were diagnosed with cancer. One hundred
ninety (28 %) were incidental cancer, of which 101 were detected on imaging
studies and 89 were detected on analysis of the surgical pathology specimens. The
incidence of thyroid cancer increased by 7.6-fold from 2003 to 2012. The
proportion of incidental cancers on imaging did not increase, but incidental
cancers found on pathology steadily increased from 6 % in 2003 to 20 % in 2012.
84 % of the cancers were papillary cancer, and the proportion of papillary cancer
was similar for both clinical and incidental cancers. Clinical cancers were
larger than incidental cancers on imaging (2.2 vs. 1.8 cm, p = 0.02). Incidental
cancers on imaging were less likely to have lateral compartment nodal metastases
(7 vs. 13 %, p < 0.001). CONCLUSIONS: Thyroid cancer diagnoses have increased at
our institution, but the proportion of incidental cancers identified on imaging
relative to clinical cancers has been stable over a decade and is not the sole
explanation for the observed increase in thyroid cancer diagnoses. Incidental
cancers on imaging are smaller in size and less likely to have lateral
compartment nodal metastases than clinical cancers.
PMID- 24357245
TI - Transumbilical single-incision laparoscopic distal pancreatectomy: primary
experience and review of the English literature.
AB - BACKGROUND: Single-incision laparoscopic surgery (SILS) may represent an
improvement over conventional laparoscopic surgery, and has been applied in many
surgical procedures. However, for pancreatic surgery, experience is rather
limited. METHODS: The clinical records of 11 cases in which transumbilical single
incision laparoscopic distal pancreatectomy (TUSI-LDP) was performed at our
institution since June 2009 were retrospectively analyzed, and all the
literatures concerning TUSI-LDP were retrospectively reviewed. RESULTS: All the
11 patients were female. The ages ranged from 20 to 73 years, with an average age
of 38.0 years. The average body mass index (BMI) was 22.67 (18.6-26.2). Most TUSI
LDPs were successfully performed, with only one conversion to multi-incision
surgery. Splenic preservation was performed in six cases. The mean operation time
was 163.18 +/- 63.18 minutes (range 95-300), and the mean intraoperative blood
loss was 159.09 +/- 181.02 ml (range 10-500 ml). The surgical wounds healed well,
with good cosmetic wound healing, and the patients were discharged from hospital
in a mean of 7.45 +/- 1.44 days (range 5-10). Only one patient developed
pancreatic leakage, which ceased spontaneously with only a drain for 61 days. The
parameters were comparable with those found in the English literature.
CONCLUSIONS: These recent experiences suggest that SILS in pancreatic surgery is
feasible for a select group of patients with relatively small lesions and low
BMI, and that, with the gradual accumulation of surgeons' experience with SILS
and improvement of laparoscopic instruments, it might become a safe option for
some patients.
PMID- 24357247
TI - Focused Assessment Sonography for Trauma (FAST) training: a systematic review.
AB - BACKGROUND: The aim of this study was to systematically review the different
methods for training Focused Assessment Sonography for Trauma (FAST), course
design, and requirements for hospital credentialing. METHODS: We searched
MEDLINE/PubMed, EMBASE, and the Cochrane database and performed a manual search
of selected papers. All papers and abstracts written in English that studied
training and education of FAST were included. Papers were critically evaluated,
looking into training methods and models of FAST, their advantages and
disadvantages, number and type of training hours, practice exams in the course,
and number of cases advised to achieve hospital credentialing. RESULTS: A total
of 52 studies were critically analyzed. The theoretical part of the courses
lasted over a median (range) of 4 (1-16) h (n = 35 studies), while the practical
part lasted over a median (range) of 4 (1-32) h (n = 34 studies). The
participants performed a median (range) of 10 (3-20) FAST exams during the
courses (n = 13 studies). The most commonly used model was the normal human model
(65 %), followed by peritoneal dialysis patients (27 %). The least used models
were animal (4 %) and cadaveric models (2 %). Each of these models had their
advantages and disadvantages. The median number (range) of FAST exams needed for
credentialing was 50 (10-200) (n = 19 studies). CONCLUSION: Standardization of
FAST training is important to improving the clinical impact of FAST. Different
models used in FAST training are complementary; each has its own advantages and
disadvantages. It is recommended that FAST courses be at least 2 days (16 h)
long. The first day should include 4 h of theory and 4 h of training on normal
human models. The second day should enforce learning using animal models, case
scenarios including video clips, or simulators.
PMID- 24357248
TI - Establishment, characterization and comparison of seven authentic anaplastic
thyroid cancer cell lines retaining clinical features of the original tumors.
AB - BACKGROUND: Anaplastic thyroid cancer (ATC) is thought to often be transformed
from pre-existing differentiated thyroid cancer. It is one of the most aggressive
malignancies and has a dismal prognosis due to its resistance to multimodal
therapies. Basic exploratory studies using authentic ATC cell lines that retain
its clinical features are necessary. We investigated the characteristics of seven
ATC cell lines newly established at our institute to confirm their possible
utility for basic studies. METHODS: Seven distinct cell lines from six patients
were established. Their molecular characteristics and sensitivities to cytotoxic
anti-cancer drugs were investigated and compared with each other, and with the
clinical features of the original tumors. RESULTS: All cells showed extensive
chromosomal abnormality and Pax8 expression, indicating human thyroid follicular
cell origin. Vascular endothelial growth factor was secreted from all cells,
suggesting possible candidacy for targeted therapy. Vimentin was expressed, but E
cadherin expression was lost in all cells but OCUT-1C, which showed different
features from those of OCUT-1F derived from the same tumor, suggesting a mixture
of cancer cell clones with various degrees of differentiation within a single ATC
tumor. Cells were likely to show sensitivity for taxanes, indicating the
usefulness of taxanes as the first-line chemotherapy. OCUT-2, a cell line with
both B-Raf and PI3 KCA mutation, demonstrated the importance of molecular target
oriented therapy. CONCLUSIONS: Basic studies using authentic ATC cell lines
retaining the clinical features of the original tumor are useful models for
investigating the mechanism of anaplastic transformation and exploring novel
therapeutic strategies.
PMID- 24357249
TI - Role of preoperative basal calcitonin levels in the timing of prophylactic
thyroidectomy in patients with germline RET mutations.
AB - BACKGROUND: The American Thyroid Association (ATA) published recommendations for
the timing of prophylactic surgery for medullary thyroid carcinoma based on the
specific mutation, patient age, family history, and serum calcitonin levels. The
aim of this study was to assess the role of preoperative basal calcitonin
(prebCt) levels in predicting the presence of medullary carcinoma of the thyroid
in patients with RET mutations. METHODS: We conducted a retrospective study in
two endocrine surgery departments. Between 1986 and 2012, a total of 32 patients
with RET mutations underwent prophylactic thyroidectomy. The patients were
stratified into four ATA risk levels: A, B, C, and D. RESULTS: All of the
patients were biologically cured. Microcarcinoma was observed in the final
pathology report for four of the 20 patients with normal prebCt (25 %) and for
nine of the 12 patients with elevated prebCt (75 %). In the level A group, four
patients with normal prebCt and one patient with elevated prebCt presented with
microcarcinoma. In the level C group, one patient with normal prebCt and six of
the seven patients with elevated prebCt (86 %) presented with microcarcinoma.
CONCLUSIONS: PrebCt can predict the presence of microcarcinoma according to
surgical pathological analysis. Patients with microcarcinoma can be biochemically
and clinically cured using prophylactic thyroidectomy.
PMID- 24357250
TI - Effect of azithromycin on lipid accumulation in immortalized human meibomian
gland epithelial cells.
PMID- 24357251
TI - Narrowing of the responsible region for severe developmental delay and autistic
behaviors in WAGR syndrome down to 1.6 Mb including PAX6, WT1, and PRRG4.
AB - Interstitial deletions of the 11p13 region are known to cause WAGR (Wilms tumor,
aniridia, genitourinary malformation, and "mental retardation") syndrome, a
contiguous gene deletion syndrome due to haploinsufficiencies of the genes in
this region, including WT1 and PAX6. Developmental delay and autistic features
are major complications of this syndrome. Previously, some genes located in this
region have been suggested as responsible for autistic features. In this study,
we identified two patients who showed the chromosomal deletions involving 11p13.
Patient 1, having an 8.6 Mb deletion of chr11p14.1p12:29,676,434-38,237,948,
exhibited a phenotype typical of WAGR syndrome and had severe developmental delay
and autistic behaviors. On the other hand, Patient 2 had a larger aberration
region in 11p14.1-p12 which was split into two regions, that is, a 2.2-Mb region
of chr11p14.1: 29,195,161-31,349,732 and a 10.5-Mb region of chr11p13p12:
32,990,627-43,492,580. As a consequence, 1.6 Mb region of the WAGR syndrome
critical region was intact between the two deletions. This patient showed no
symptom of WAGR syndrome and no autistic behaviors. Therefore, the region
responsible for severe developmental delay and autistic features on WAGR syndrome
can be narrowed down to the region remaining intact in Patient 2. Thus, the
unique genotype identified in this study suggested that haploinsufficiencies of
PAX6 or PRRG4 included in this region are candidate genes for severe
developmental delay and autistic features characteristic of WAGR syndrome.
PMID- 24357252
TI - Solid/Hollow depots for drug delivery, part 1: effect of drug characteristics and
polymer molecular weight on the phase-inversion dynamics, depot morphology, and
drug release.
AB - The objective of this research was to evaluate the effect of drug characteristics
and polymer molecular weight (MW) on phase-inversion dynamics, depot morphology,
and drug release in injectable in situ depot-forming drug delivery systems. Two
poly(lactide-co-glycolide) (50:50) polymers with different MW (RG502 and RG504)
and two drugs with different hydrophilicity (metoclopramide salt and
metoclopramide base) were studied here. The drug release from injectable depots,
the polymer MW changes, and the cross-sectional depot morphologies were
investigated, respectively. The results show that the initial drug release from
high-MW polymer RG504 was always faster than that from low-MW polymer RG502,
regardless of the drug type. Interestingly, depot morphology shows the
development of a hollow core for RG502, whereas RG504 forms a solid core. The
relationship of the depot morphology to release kinetics is proposed based on
these observations. The use of basic drug catalyzes polymer degradation, during
processing and over time. These affect starting MW and subsequent MW, and the
effect on release kinetics is consistent with the general effects of MW. This
research suggests that the polymer MW is an important effect on the polymer phase
inversion kinetics, and thus the resultant depot morphology.
PMID- 24357253
TI - Optical wavelength filters based on photonic confinement in semiconductor
nanowire homojunctions.
PMID- 24357254
TI - Impact of cigarette smoking on P2Y12 receptor binding activity before and after
clopidogrel therapy in patients with coronary artery disease.
AB - Smoking enhances the P2Y12 receptor inhibitory effects of clopidogrel. Nicotine
increases P2Y12 receptor expression in platelet lysates from healthy volunteers.
However, the impact of cigarette smoking on platelet P2Y12 receptor binding in
clopidogrel-treated patients with coronary artery disease (CAD) is unknown.
Clopidogrel-naive patients with stable CAD (n = 20) were enrolled and stratified
according to smoking status. P2Y12 receptor binding activity was determined by
radioligand receptor binding prior and 24 h after a 600-mg loading dose of
clopidogrel. Baseline P2Y12 receptor binding was 1.8-fold higher in smokers
compared with nonsmokers. After a 600-mg loading dose of clopidogrel, smokers
showed a 6.4-fold reduction in P2Y12 receptor binding indicative of marked
clopidogrel-mediated blockade, while there were minimal changes among nonsmokers.
Among patients with stable CAD, smokers have more P2Y12 receptor binding than
nonsmokers and have a higher degree of clopidogrel-mediated platelet inhibition.
PMID- 24357255
TI - A population estimate of chimpanzees (Pan troglodytes schweinfurthii) in the
Ugalla region using standard and spatially explicit genetic capture-recapture
methods.
AB - Population parameters such as size, density, and distribution of a species across
a landscape are important metrics that inform conservation science and are key to
management strategies. In this study, we used genetic capture-recapture methods
to estimate the population size and density of the little-studied chimpanzees in
the Ugalla region of western Tanzania. From 237 fecal samples collected non
invasively over a 10-month period, we identified a minimum of 113 individuals.
Based on the two-innate rate method (TIRM) modeled in the software capwire, we
obtained a maximum-likelihood estimate of 322 (CI 227-373) individuals over the
624 km(2) area surveyed. Using a spatially explicit capture-recapture (SECR)
method, we estimated a population density of 0.25 (CI 0.16-0.38)
individuals/km(2) . Observations of nests and search effort data revealed areas
of more intense usage. The findings of this study are an important step in the
characterization of the Ugalla chimpanzees, and substantially improve our
understanding of the number of chimpanzees that occupy this savanna-woodland
region at the easternmost extent of the geographic range of this endangered
subspecies.
PMID- 24357256
TI - Foreign bodies in the oral cavity of very young children are rare and difficult
to diagnose.
PMID- 24357257
TI - Cesarean scar pregnancy and early placenta accreta share common histology.
AB - OBJECTIVE: To determine, by evaluation of histological slides, images and
descriptions of early (second-trimester) placenta accreta (EPA) and placental
implantation in cases of Cesarean scar pregnancy (CSP), whether these are
pathologically indistinguishable and whether they both represent different stages
in the disease continuum leading to morbidly adherent placenta in the third
trimester. METHODS: The database of a previously published review of CSP and EPA
was used to identify articles with histopathological descriptions and electronic
images for pathological review. When possible, microscopic slides and/or paraffin
blocks were obtained from the original researchers. We also included from our own
institutions cases of CSP and EPA for which pathology specimens were available.
Two pathologists examined all the material independently and, blinded to each
other's findings, provided a pathological diagnosis based on microscopic
appearance. Interobserver agreement in diagnosis was determined. RESULTS: Forty
articles were identified, which included 31 cases of CSP and 13 cases of EPA
containing histopathological descriptions and/or images of the pathology. We
additionally included six cases of CSP and eight cases of EPA from our own
institutions, giving a total of 58 cases available for histological evaluation
(37 CSP and 21 EPA) containing clear definitions of morbidly adherent placenta.
In the 29 cases for which images/slides were available for histopathological
evaluation, both pathologists attested to the various degrees of myometrial
and/or scar tissue invasion by placental villi with scant or no intervening
decidua, consistent with the classic definition of morbidly adherent placenta.
Based on the reviewed material, cases with a diagnosis of EPA and those with a
diagnosis of CSP showed identical histopathological features. Interobserver
correlation was high (kappa = 0.93). CONCLUSIONS: EPA and placental implantation
in CSP are histopathologically indistinguishable and may represent different
stages in the disease continuum leading to morbidly adherent placenta in the
third trimester.
PMID- 24357258
TI - Fibrinolytic agents for peripheral arterial occlusion.
AB - BACKGROUND: Peripheral arterial thrombolysis is used in the management of
peripheral arterial ischaemia. Streptokinase was originally used but safety
concerns led to a search for other agents. Urokinase and recombinant tissue
plasminogen activator (rt-PA) have increasingly become established as first line
agents for peripheral arterial thrombolysis. Potential advantages of these agents
include improved safety, greater efficacy and a more rapid response. Recently
drugs such as pro-urokinase, recombinant staphylokinase and alfimperase have been
introduced. This is an update of a review first published in 2010. OBJECTIVES: To
determine which fibrinolytic agents are most effective in peripheral arterial
ischaemia. SEARCH METHODS: For this update the Cochrane Peripheral Vascular
Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register
(last searched March 2013) and CENTRAL (2013, Issue 3) for randomised controlled
trials (RCTs) comparing fibrinolytic agents to treat peripheral arterial
ischaemia. SELECTION CRITERIA: RCTs comparing fibrinolytic agents to treat
peripheral arterial occlusion. DATA COLLECTION AND ANALYSIS: Data were analysed
for the outcomes vessel patency, time to lysis, limb salvage, amputation, death,
complications including major haemorrhage, stroke, and distal embolization. MAIN
RESULTS: Five RCTs involving a total of 687 participants with a range of clinical
indications were included. No new studies were included in this update. In one
three-pronged study, vessel patency was greater with intra-arterial recombinant
tissue plasminogen activator (rt-PA) than with intra-arterial streptokinase (P <
0.04) or intravenous rt-PA (P < 0.01). In participants with peripheral arterial
occlusion there was no statistically significant difference in limb salvage at 30
days with either urokinase or rt-PA, though this may reflect the small numbers in
the studies. Incidences of haemorrhagic complications varied with fibrinolytic
regime but there was no statistically significant difference between intra
arterial urokinase and intra-arterial rt-PA. In the three-pronged study
intravenous rt-PA and intra-arterial streptokinase were associated with a
significantly higher risk of haemorrhagic complications than with intra-arterial
rt-PA (P < 0.05). AUTHORS' CONCLUSIONS: There is some evidence to suggest that
intra-arterial rt-PA is more effective than intra-arterial streptokinase or
intravenous rt-PA in improving vessel patency in people with peripheral arterial
occlusion. There was no evidence that rt-PA was more effective than urokinase for
patients with peripheral arterial occlusion and some evidence that initial lysis
may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic
complications were not statistically significantly greater with rt-PA than with
other regimes. However, all of the findings come from small studies and a general
paucity of results means that it is not possible to draw clear conclusions.
PMID- 24357259
TI - Comparison of self-reported physical activity in children and adolescents before
and during cancer treatment.
AB - BACKGROUND: Physical activities are important for the development of children and
increasing evidence suggests beneficial effects of physical activity promotion
during cancer treatment as well. The present study aimed at evaluating the
current need of exercise interventions in pediatric cancer patients undergoing
acute treatment and identifying risk factors for inactivity. PROCEDURE: Data
about self-reported physical activity before and during treatment was collected
in a cross-sectional design with the physical activity questionnaire from the
German Health Interview and Examination Survey for Children and Adolescents
(KiGGS) in a modified cancer specific version. RESULTS: One hundred thirty
pediatric cancer patients with various entities were questioned 3.0 +/- 1.6
months since diagnosis. Patients' activity levels before diagnosis mainly matched
reference values for healthy children in Germany. Reductions during treatment
affected all dimensions of daily physical activities and minutes of exercise per
week decreased significantly (P < 0.001). Largest reductions of physical
activities during treatment were identified for bone tumor patients and in
patient stays. CONCLUSIONS: Due to the well known importance of physical activity
during childhood and the identified risk of inactivity during cancer treatment,
supervised exercise interventions should be implemented into acute treatment
phase to enhance activity levels and ensure a continuously support by qualified
exercise professionals.
PMID- 24357260
TI - Secretion of interferon gamma from human immune cells is altered by exposure to
tributyltin and dibutyltin.
AB - Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants
found in food, beverages, and human blood samples. Both of these butyltins (BTs)
interfere with the ability of human natural killer (NK) cells to lyse target
cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor
alpha (TNFalpha) from human immune cells in vitro. The capacity of BTs to
interfere with secretion of other pro-inflammatory cytokines has not been
examined. Interferon gamma (IFNgamma) is a modulator of adaptive and innate
immune responses, playing an important role in overall immune competence. This
study shows that both TBT and DBT alter secretion of IFNgamma from human immune
cells. Peripheral blood cell preparations that were increasingly reconstituted
were used to determine if exposures to either TBT or DBT affected IFNgamma
secretion and how the makeup of the cell preparation influenced that effect.
IFNgamma secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200
- 2.5 nM) and DBT (5 - 0.05 uM) in highly enriched human NK cells, a monocyte
depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered
IFNgamma secretion from immune cells at most of the conditions tested (either
increasing or decreasing secretion). However, there was significant variability
among donors as to the concentrations and time points that showed changes as well
as the baseline secretion of IFNgamma. The majority of donors showed an increase
in IFNgamma secretion in response to at least one concentration of TBT or DBT at
a minimum of one length of exposure.
PMID- 24357263
TI - Kinin B1 receptor deficiency attenuates cisplatin-induced acute kidney injury by
modulating immune cell migration.
AB - Cisplatin is a chemotherapeutic agent that causes severe renal dysfunction. The
kinin B1 receptor has been associated with the migration of immune cells to
injured tissue as well as with renal inflammation. To examine the role of the
kinin B1 receptor in cisplatin-induced acute kidney injury, we used kinin B1
receptor knockout mice and treatment with a receptor antagonist before and after
cisplatin administration. Cisplatin injection caused exacerbation of renal
macrophage and neutrophil migration, higher levels of serum creatinine and blood
urea, upregulation of B1 receptor mRNA and an increase in pro-inflammatory
cytokines expression. B1 receptor knockout mice exhibited a reduction in serum
creatinine and blood urea levels, diminished apoptosis, and decreased cisplatin
induced upregulation of inflammatory components. Moreover, treatment with the B1
receptor antagonist prior to cisplatin administration normalized serum
creatinine, blood urea levels, protected from acute tubular necrosis, apoptosis
related genes, and prevented upregulation of pro-inflammatory cytokines. Thus, we
propose that kinins have an important role in cisplatin-induced acute kidney
injury by impairing immune cells migration to renal tissue during cisplatin
nephrotoxicity. KEY MESSAGE: Kinin B1 receptor is upregulated after cisplatin
exposure. Kinin B1 receptor deficiency diminishes the nephrotoxicity caused by
cisplatin. Kinin B1 receptor deficiency ameliorates the inflammatory response.
Kinin B1 receptor deficiency diminishes apoptosis caused by cisplatin. Kinin B1
receptor antagonism ameliorates renal function after cisplatin injection.
PMID- 24357264
TI - Intraperitoneal injection improves the uptake of nanoparticle-labeled high
density lipoprotein to atherosclerotic plaques compared with intravenous
injection: a multimodal imaging study in ApoE knockout mice.
AB - BACKGROUND: The aim of this study was to assess whether high-density lipoprotein
(HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum
dots was able to detect atherosclerotic lesions in mice after intravenous and
intraperitoneal injection by multimodal imaging. METHODS AND RESULTS:
Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light
scattering and size exclusion chromatography with subsequent cholesterol and
fluorescence measurements. For biodistribution and blood clearance studies, NP
HDL(SPIOs) radiolabeled with (59)Fe (NP-HDL(59Fe-SPIOs)) were injected
intravenously or intraperitoneally into ApoE knockout mice (n=6), and
radioactivity was measured using a gamma counter. NP-HDL accumulation within
atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex
vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and
histological analysis (n=3). Statistical analyses were performed using a 2-tailed
Student t-test. In vitro characterization of NP-HDL confirmed properties similar
to endogenous HDL. Blood concentration time curves showed a biexponential
decrease for the intravenous injection, whereas a slow increase followed by a
steady state was noted for intraperitoneal injection. Radioactivity measurements
showed predominant accumulation in the liver and spleen after both application
approaches. NP-HDL(59Fe-SPIOs) uptake into atherosclerotic plaques increased
significantly after intraperitoneal compared with intravenous injection (P<0.01).
In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions
after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray
fluorescence microscopy, confocal fluorescence microscopy, and histological
analysis. CONCLUSIONS: In vivo MRI and ex vivo multimodal imaging of
atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application
improves the uptake within vessel wall lesions compared with intravenous
injection.
PMID- 24357265
TI - Fish cholinesterases as biomarkers of sublethal effects of organophosphorus and
carbamates in tissues of Labeo rohita.
AB - Organophosphates and carbamates are major agrochemicals that strongly affect
different neuroenzymes and the growth of various fish species. Here, we study the
effect of sublethal concentrations of profenofos and carbofuran on the activity
of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and the
associated health risk in fish. Labeo rohita fingerlings were exposed to three
sublethal concentrations of profenofos and carbofuran. The minimum cholinesterase
activities in the brain, gills, muscle, kidney, liver, and blood were after
exposure to profenofos (0.06 mg/L). The minimum AChE and BuChE activities in the
brain, gills, muscle, kidney, liver, and blood were after exposure to carbofuran
(0.28 and 0.198 mg/L). Exposure to both types of pesticides affected the
functions of these organs, including metabolism and neurotransmission, to various
extents at different exposure concentrations. These findings suggest that they
are required to be properly monitored in the environment, to reduce their toxic
effects on nontarget organisms.
PMID- 24357266
TI - Mutation p.Leu128Pro in the 1A domain of K16 causes pachyonychia congenita with
focal palmoplantar keratoderma in a Chinese family.
AB - Pachyonychia congenita (PC), a rare autosomal dominant disorder characterized by
hypertrophic nail dystrophy, is classified into two main clinical subtypes: PC-1
and PC-2. PC-1 is associated with mutations in the KRT6A or KRT16 genes, whereas
PC-2 is linked to KRT6B or KRT17 mutations. Blood samples were collected from
three generations of a new Chinese PC-1 family, including three PC patients and
five unaffected family members. A novel missense mutation p.Leu128Pro (c.383T>C)
was identified in a highly conserved helix motif in domain 1A of K16. The disease
haplotype carried the mutation and cosegregated with the affection status.
PolyPhen2 and SIFTS analysis rated the substitution as probably damaging; Swiss
Model analysis indicated that the structure of the mutant protein contained an
unnormal alpha-helix. Overexpression of mutant protein in cultured cells led to
abnormal cell morphology. CONCLUSION: The wider spectrum of KRT16 mutations
suggests that changes in codons 125, 127, and 132 are most commonly responsible
for PC-1 and that proline substitution mutations at codons 127 or 128 may produce
more severe disease. This study extends the KRT16 mutation spectrum and adds new
information on the clinical and genetic diversity of PC.
PMID- 24357262
TI - The chick embryo as an expanding experimental model for cancer and cardiovascular
research.
AB - A long and productive history in biomedical research defines the chick as a model
for human biology. Fundamental discoveries, including the description of
directional circulation propelled by the heart and the link between oncogenes and
the formation of cancer, indicate its utility in cardiac biology and cancer.
Despite the more recent arrival of several vertebrate and invertebrate animal
models during the last century, the chick embryo remains a commonly used model
for vertebrate biology and provides a tractable biological template. With new
molecular and genetic tools applied to the avian genome, the chick embryo is
accelerating the discovery of normal development and elusive disease processes.
Moreover, progress in imaging and chick culture technologies is advancing real
time visualization of dynamic biological events, such as tissue morphogenesis,
angiogenesis, and cancer metastasis. A rich background of information, coupled
with new technologies and relative ease of maintenance, suggest an expanding
utility for the chick embryo in cardiac biology and cancer research.
PMID- 24357268
TI - Polycyclic aromatic hydrocarbons in urban soils of Hangzhou: status,
distribution, sources, and potential risk.
AB - Concentration, composition profile, spatial distribution, sources, and health
risk of 16 polycyclic aromatic hydrocarbons (PAHs) were analyzed in 69 surface
soil samples collected from Hangzhou urban districts. ?PAHs ranged from 180.77 to
1,981.45 MUg kg(-1) with a mean of 611.28 MUg kg(-1). Among different functional
areas, a higher level of PAHs was found in the roadsides, followed by commercial
districts, residential areas, parks, and greenbelts. The composition of PAHs was
characterized by high molecular weight PAHs (4 ~ 6 rings). Principal component
analysis (PCA) and PAH isomeric ratios indicated that PAHs mainly originated from
combustion, especially vehicle exhaust. The incremental lifetime cancer risks
(ILCRs) associated with exposures to PAHs in soil were calculated separately for
children and adults under normal and extreme conditions. The results showed that
ILCRs for urban soil of Hangzhou were acceptable. However, attentions should be
attracted on the sites of high PAH concentrations because the ILCRs were closed
to 10(-4) under extreme conditions, especially for children.
PMID- 24357267
TI - Thiamine-responsive megaloblastic anemia syndrome with Ebstein anomaly: a case
report.
AB - Thiamine-responsive megaloblastic anemia (TRMA) or Roger syndrome is a rare
autosomal recessive disorder characterized by the occurrence of multiple clinical
manifestations including megaloblastic anemia, diabetes mellitus, and
sensorineural deafness. A few patients have been also described with congenital
cardiac malformations. The patients usually respond to treatment with
pharmacological doses of thiamine. Mutations in the SLC19A2 gene, located at
chromosome 1q24.2, are responsible for this syndrome. Here, we present two new
Iranian TRMA patients who were homozygous for c.697C > T mutation in the SLC19A2
gene. On follow-up, one of the patients showed Ebstein anomaly. CONCLUSION: The
present study confirms the variability of the clinical manifestations caused by
the same mutation within patients with TRMA syndrome. Therefore, follow-up of the
affected children should be considered.
PMID- 24357269
TI - The fatty acid compositions of several plant seed oils belong to Leguminosae and
Umbelliferae families.
AB - In samples with 1,009, 7,723, 7,618, 7,618, 1,004 and 1,009 number, oleic acid
were found as 62.0, 77.0, 74.84, 71.55, 54.52 and 62.30 %, respectively. In other
samples, oleic acid content was determined between 17.43 % (1,589) and 34.86 %
(1,298). Linoleic acid content of seed oils ranged from 6.52 % (7,727) to 57.29 %
(1,501). In addition, linolenic acid content was found between 0.22 % (7,618) and
46.91 % (1,589). Palmitic acid content of samples changed between 2.03 % (7,727)
and 19.81 % (1,298). Capric acid was found at high level in 1,009 (8.53 %), 7,727
(37.31 %) and 1,004 (8.28 %) samples. Caproic acid was found in only 7,727 (3.38
%).
PMID- 24357271
TI - (31) P MR spectroscopic imaging combined with (1) H MR spectroscopic imaging in
the human prostate using a double tuned endorectal coil at 7T.
AB - PURPOSE: Improved diagnostic sensitivity could be obtained in cancer detection
and staging when individual compounds of the choline pool can be detected.
Therefore, a novel coil design is proposed, providing the ability to acquire both
(1) H and (31) P magnetic resonance spectroscopic imaging (MRSI) in patients with
prostate cancer. METHODS: A two-element (1) H/(31) P endorectal coil was designed
by adjusting a commercially available 3T endorectal coil. The two-element coil
setup was interfaced as a transceiver to a whole body 7T MR scanner. Simulations
and phantom measurements were performed to compare the efficiency of the coil.
(1) H MRSI and (31) P MRSI were acquired in vivo in prostate cancer patients.
RESULTS: The efficiency of the (1) H/(31) P coil is comparable to the dual
channel (1) H coil previously published. Individually distinguishable
phospholipid metabolites in the in vivo (31) P spectra were: phosphoethanolamine,
phosphocholine, phosphate, glycerophosphoethanolamine, glycerophosphocholine,
phosphocreatine, and adenosine triposphate. (1) H MRSI was performed within the
same scan session, visualizing choline, polyamines, creatine, and citrate.
CONCLUSION: (1) H MRSI and (31) P MRSI can be acquired in the human prostate at
7T within the same scan session using an endorectal coil matched and tuned for
(1) H (quadrature) and (31) P (linear) without the need of cable traps and with
negligible efficiency losses in the (1) H and (31) P channel.
PMID- 24357272
TI - Pd(0)-catalyzed regio- and stereoselective cyclization of alkynes: selective
synthesis of (E)-4-(isobenzofuran-1(3H)-ylidene)-1,2,3,4-tetrahydroisoquinolines
and aze/oxepinoindoles.
AB - Palladium-catalyzed highly regio- and stereoselective 6-exo-dig and 7-endo-dig
cyclization of functionalized propargylic compounds has been developed for the
synthesis of (E)-4-(isobenzofuran-1(3H)-ylidene)-1,2,3,4-tetrahydroisoquinolines
and aze/oxepinoindoles.
PMID- 24357270
TI - Dexamethasone for preventing postoperative sore throat: a meta-analysis of
randomized controlled trials.
AB - BACKGROUND: Postoperative sore throat (POST) is a common complication following
tracheal intubation. The effectiveness of prophylactic dexamethasone on POST
needs further elucidation. AIMS: To evaluate the effectiveness and safety of
intravenous dexamethasone for the prevention of POST in patients undergoing
endotracheal intubation. METHODS: Studies were identified by literature searches
of PubMed, Embase, and the Cochrane database. Systematic review was performed by
two independent investigators. RESULTS: We summarized 7 RCTs including 727
participants. Intravenous dexamethasone significantly reduced the risk of POST at
24 h [pooled risk ratio (RR) = 0.676; 95 % confidence interval (CI) 0.494-0.925;
P = 0.014; heterogeneity test, I (2) = 45.8 %], as well as alleviating its
severity [standardized mean difference (SMD) = -1.15; 95 % CI -1.86 to -0.45; P =
0.002; heterogeneity test, I (2) = 91.7 %]. Further sub-group analysis indicated
a significant relationship between dexamethasone and reduced risk of POST when
its dose was over 0.1 mg/kg. No severe adverse effects were reported.
CONCLUSIONS: Our results suggest that intravenous dexamethasone reduces the risk
and severity of POST from intubation at 24 h. The effective dosage of
dexamethasone for preventing the risk of POST appeared to be over 0.1 mg/kg.
PMID- 24357273
TI - Cancer immunotherapy.
PMID- 24357278
TI - Paleontology. Mega-eruptions drove the mother of mass extinctions.
PMID- 24357279
TI - Astronomy. Money woes cloud future of workhorse U.S. telescopes.
PMID- 24357281
TI - Materials science. Amid superconductor debate, clash of physics titans resumes.
PMID- 24357280
TI - Science funding. U.S. budget deal offers researchers some sequester relief.
PMID- 24357282
TI - Arms control. Scientists campaign against killer robots.
PMID- 24357283
TI - Immunology. Swine flu connection provides clues about narcolepsy.
PMID- 24357284
TI - Breakthrough of the year 2013. Cancer immunotherapy.
PMID- 24357285
TI - 2013 Runners-Up. Genetic microsurgery for the masses.
PMID- 24357286
TI - 2013 Runners-Up. CLARITY makes it perfectly clear.
PMID- 24357287
TI - 2013 Runners-Up. Human cloning at last.
PMID- 24357288
TI - 2013 Runners-Up. Dishing up mini-organs.
PMID- 24357289
TI - 2013 Runners-Up. Cosmic particle accelerators identified.
PMID- 24357290
TI - 2013 Runners-Up. Newcomer juices up the race to harness sunlight.
PMID- 24357291
TI - 2013 Runners-Up. To sleep, perchance to clean.
PMID- 24357292
TI - 2013 Runners-Up. Your microbes, your health.
PMID- 24357293
TI - 2013 Runners-Up. In vaccine design, looks do matter.
PMID- 24357294
TI - Breakthrough of the year 2013. How we did in 2013 and...
PMID- 24357295
TI - Breakthrough of the year 2013. ...Areas to watch in 2014.
PMID- 24357296
TI - Breakthrough of the year 2013. Notable developments.
PMID- 24357297
TI - Sea-level rise by 2100.
PMID- 24357298
TI - Credit for impact theory.
PMID- 24357300
TI - Social Security and Medicare in the black.
PMID- 24357301
TI - Mercury toxicity in children.
PMID- 24357302
TI - Education. Open learning at a distance: lessons for struggling MOOCs.
PMID- 24357303
TI - Evolution. How cooperation defeats cheats.
PMID- 24357304
TI - Medicine. A common pathway for a rare disease?
PMID- 24357305
TI - Microbiology. No barriers to cellulose breakdown.
PMID- 24357306
TI - Genomics. Genomic clues to the ancestral flowering plant.
PMID- 24357307
TI - Biochemistry. Enzyme kinetics, past and present.
PMID- 24357308
TI - Geochemistry. Reformulating table salt under pressure.
PMID- 24357309
TI - Cell Biology. Ronning after the adiponectin receptors.
PMID- 24357310
TI - IBI* series winner. DNA barcoding from NYC to Belize.
PMID- 24357312
TI - Constraining exoplanet mass from transmission spectroscopy.
AB - Determination of an exoplanet's mass is a key to understanding its basic
properties, including its potential for supporting life. To date, mass
constraints for exoplanets are predominantly based on radial velocity (RV)
measurements, which are not suited for planets with low masses, large semimajor
axes, or those orbiting faint or active stars. Here, we present a method to
extract an exoplanet's mass solely from its transmission spectrum. We find good
agreement between the mass retrieved for the hot Jupiter HD 189733b from
transmission spectroscopy with that from RV measurements. Our method will be able
to retrieve the masses of Earth-sized and super-Earth planets using data from
future space telescopes that were initially designed for atmospheric
characterization.
PMID- 24357311
TI - Horizontal transfer of entire genomes via mitochondrial fusion in the angiosperm
Amborella.
AB - We report the complete mitochondrial genome sequence of the flowering plant
Amborella trichopoda. This enormous, 3.9-megabase genome contains six genome
equivalents of foreign mitochondrial DNA, acquired from green algae, mosses, and
other angiosperms. Many of these horizontal transfers were large, including
acquisition of entire mitochondrial genomes from three green algae and one moss.
We propose a fusion-compatibility model to explain these findings, with Amborella
capturing whole mitochondria from diverse eukaryotes, followed by mitochondrial
fusion (limited mechanistically to green plant mitochondria) and then genome
recombination. Amborella's epiphyte load, propensity to produce suckers from
wounds, and low rate of mitochondrial DNA loss probably all contribute to the
high level of foreign DNA in its mitochondrial genome.
PMID- 24357313
TI - Detection of Berry's phase in a Bulk Rashba semiconductor.
AB - The motion of electrons in a solid has a profound effect on its topological
properties and may result in a nonzero Berry's phase, a geometric quantum phase
encoded in the system's electronic wave function. Despite its ubiquity, there are
few experimental observations of Berry's phase of bulk states. Here, we report
detection of a nontrivial pi Berry's phase in the bulk Rashba semiconductor BiTeI
via analysis of the Shubnikov-de Haas (SdH) effect. The extremely large Rashba
splitting in this material enables the separation of SdH oscillations, stemming
from the spin-split inner and outer Fermi surfaces. For both Fermi surfaces, we
observe a systematic pi-phase shift in SdH oscillations, consistent with the
theoretically predicted nontrivial pi Berry's phase in Rashba systems.
PMID- 24357314
TI - Relaxation mechanism of the hydrated electron.
AB - The relaxation dynamics of the photoexcited hydrated electron have been subject
to conflicting interpretations. Here, we report time-resolved photoelectron
spectra of hydrated electrons in a liquid microjet with the aim of clarifying
ambiguities from previous experiments. A sequence of three ultrashort laser
pulses (~100 femtosecond duration) successively created hydrated electrons by
charge-transfer-to-solvent excitation of dissolved anions, electronically excited
these electrons via the s->p transition, and then ejected them into vacuum. Two
distinct transient signals were observed. One was assigned to the initially
excited p-state with a lifetime of ~75 femtoseconds, and the other, with a
lifetime of ~400 femtoseconds, was attributed to s-state electrons just after
internal conversion in a nonequilibrated solvent environment. These assignments
support the nonadiabatic relaxation model.
PMID- 24357315
TI - Dynamical resonances accessible only by reagent vibrational excitation in the F +
HD->HF + D reaction.
AB - Experimental limitations in vibrational excitation efficiency have previously
hindered investigation of how vibrational energy might mediate the role of
dynamical resonances in bimolecular reactions. Here, we report on a high
resolution crossed-molecular-beam experiment on the vibrationally excited HD(v =
1) + F -> HF + D reaction, in which two broad peaks for backward-scattered HF(v'
= 2 and 3) products clearly emerge at collision energies of 0.21 kilocalories per
mole (kcal/mol) and 0.62 kcal/mol from differential cross sections measured over
a range of energies. We attribute these features to excited Feshbach resonances
trapped in the peculiar HF(v' = 4)-D vibrationally adiabatic potential in the
postbarrier region. Quantum dynamics calculations on a highly accurate potential
energy surface show that these resonance states correlate to the HD(v' = 1) state
in the entrance channel and therefore can only be accessed by the vibrationally
excited HD reagent.
PMID- 24357316
TI - Unexpected stable stoichiometries of sodium chlorides.
AB - Sodium chloride (NaCl), or rocksalt, is well characterized at ambient pressure.
As a result of the large electronegativity difference between Na and Cl atoms, it
has highly ionic chemical bonding (with 1:1 stoichiometry dictated by charge
balance) and B1-type crystal structure. By combining theoretical predictions and
diamond anvil cell experiments, we found that new materials with different
stoichiometries emerge at high pressures. Compounds such as Na3Cl, Na2Cl, Na3Cl2,
NaCl3, and NaCl7 are theoretically stable and have unusual bonding and electronic
properties. To test this prediction, we synthesized cubic and orthorhombic NaCl3
and two-dimensional metallic tetragonal Na3Cl. These experiments establish that
compounds violating chemical intuition can be thermodynamically stable even in
simple systems at nonambient conditions.
PMID- 24357317
TI - Brood parasitism and the evolution of cooperative breeding in birds.
AB - The global distribution of cooperatively breeding birds is highly uneven, with
hotspots in Australasia and sub-Saharan Africa. The ecological drivers of this
distribution remain enigmatic yet could yield insights into the evolution and
persistence of cooperative breeding. We report that the global distributions of
avian obligate brood parasites and cooperatively breeding passerines are tightly
correlated and that the uneven phylogenetic distribution of cooperative breeding
is associated with the uneven targeting of hosts by brood parasites. With a long
term field study, we show that brood parasites can acquire superior care for
their young by targeting cooperative breeders. Conversely, host defenses against
brood parasites are strengthened by helpers at the nest. Reciprocally selected
interactions between brood parasites and cooperative breeders may therefore
explain the close association between these two breeding systems.
PMID- 24357318
TI - C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine
response.
AB - The inbred mouse C57BL/6J is the reference strain for genome sequence and for
most behavioral and physiological phenotypes. However, the International Knockout
Mouse Consortium uses an embryonic stem cell line derived from a related C57BL/6N
substrain. We found that C57BL/6N has a lower acute and sensitized response to
cocaine and methamphetamine. We mapped a single causative locus and identified a
nonsynonymous mutation of serine to phenylalanine (S968F) in Cytoplasmic FMRP
interacting protein 2 (Cyfip2) as the causative variant. The S968F mutation
destabilizes CYFIP2, and deletion of the C57BL/6N mutant allele leads to acute
and sensitized cocaine-response phenotypes. We propose that CYFIP2 is a key
regulator of cocaine response in mammals and present a framework to use mouse
substrains to identify previously unknown genes and alleles regulating behavior.
PMID- 24357319
TI - Revealing nature's cellulase diversity: the digestion mechanism of
Caldicellulosiruptor bescii CelA.
AB - Most fungi and bacteria degrade plant cell walls by secreting free, complementary
enzymes that hydrolyze cellulose; however, some bacteria use large enzymatic
assemblies called cellulosomes, which recruit complementary enzymes to protein
scaffolds. The thermophilic bacterium Caldicellulosiruptor bescii uses an
intermediate strategy, secreting many free cellulases that contain multiple
catalytic domains. One of these, CelA, comprises a glycoside hydrolase family 9
and a family 48 catalytic domain, as well as three type III cellulose-binding
modules. In the saccharification of a common cellulose standard, Avicel, CelA
outperforms mixtures of commercially relevant exo- and endoglucanases. From
transmission electron microscopy studies of cellulose after incubation with CelA,
we report morphological features that suggest that CelA not only exploits the
common surface ablation mechanism driven by general cellulase processivity, but
also excavates extensive cavities into the surface of the substrate. These
results suggest that nature's repertoire of cellulose digestion paradigms remain
only partially discovered and understood.
PMID- 24357320
TI - Assembly and validation of the genome of the nonmodel basal angiosperm Amborella.
AB - Genome sequencing with next-generation sequence (NGS) technologies can now be
applied to organisms pivotal to addressing fundamental biological questions, but
with genomes previously considered intractable or too expensive to undertake.
However, for species with large and complex genomes, extensive genetic and
physical map resources have, until now, been required to direct the sequencing
effort and sequence assembly. As these resources are unavailable for most
species, assembling high-quality genome sequences from NGS data remains
challenging. We describe a strategy that uses NGS, fluorescence in situ
hybridization, and whole-genome mapping to assemble a high-quality genome
sequence for Amborella trichopoda, a nonmodel species crucial to understanding
flowering plant evolution. These methods are applicable to many other organisms
with limited genomic resources.
PMID- 24357321
TI - CRL4 complex regulates mammalian oocyte survival and reprogramming by activation
of TET proteins.
AB - The duration of a woman's reproductive period is determined by the size and
persistence of a dormant oocyte pool. Specific oocyte genes are essential for
follicle maintenance and female fertility. The mechanisms that regulate the
expression of these genes are poorly understood. We found that a cullin-ring
finger ligase-4 (CRL4) complex was crucial in this process. Oocyte-specific
deletion of the CRL4 linker protein DDB1 or its substrate adaptor VPRBP (also
known as DCAF1) caused rapid oocyte loss, premature ovarian insufficiency, and
silencing of fertility maintaining genes. CRL4(VPRBP) activates the TET
methylcytosine dioxygenases, which are involved in female germ cell development
and zygote genome reprogramming. Hence, CRL4(VPRBP) ubiquitin ligase is a
guardian of female reproductive life in germ cells and a maternal reprogramming
factor after fertilization.
PMID- 24357324
TI - Successful treatment of refractory aortitis in antineutrophil cytoplasmic
antibody-associated vasculitis using tocilizumab.
AB - A 47-year-old Japanese woman developed antineutrophil cytoplasmic antibody (ANCA)
associated vasculitis (AAV) complicated by a rare combination of aortitis and
hypertrophic pachymeningitis. Despite the therapy with prednisolone and
cyclophosphamide, the aortitis was not ameliorated. However, after
cyclophosphamide was replaced with intravenous tocilizumab, the aortitis was
improved, and the prednisolone dose was successfully tapered to 4 mg/day without
elevation in C-reactive protein and myeloperoxidase ANCA (MPO-ANCA) levels.
Several studies have reported that tocilizumab is effective for aortitis
associated with Takayasu's arteritis and giant cell arteritis. On the other hand,
we succeeded to improve the aortitis in AAV with monthly administration of
tocilizumab. Moreover, we successfully controlled disease activity and enabled
the tapering of prednisolone to 4 mg/day without relapses of AAV symptoms and
elevated MPO-ANCA levels. It indicates that tocilizumab may be therapeutically
beneficial for not only aortitis but also AAV itself. In conclusion, tocilizumab
was effective in treating glucocorticoid- and cyclophosphamide-resistant AAV
associated aortitis. This is the first report demonstrating the successful
treatment of AAV-associated aortitis using tocilizumab.
PMID- 24357322
TI - Serial femtosecond crystallography of G protein-coupled receptors.
AB - X-ray crystallography of G protein-coupled receptors and other membrane proteins
is hampered by difficulties associated with growing sufficiently large crystals
that withstand radiation damage and yield high-resolution data at synchrotron
sources. We used an x-ray free-electron laser (XFEL) with individual 50
femtosecond-duration x-ray pulses to minimize radiation damage and obtained a
high-resolution room-temperature structure of a human serotonin receptor using
sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as
lipidic cubic phase. Compared with the structure solved by using traditional
microcrystallography from cryo-cooled crystals of about two orders of magnitude
larger volume, the room-temperature XFEL structure displays a distinct
distribution of thermal motions and conformations of residues that likely more
accurately represent the receptor structure and dynamics in a cellular
environment.
PMID- 24357325
TI - Consensus opinion of a North American Working Group regarding the classification
of digital ulcers in systemic sclerosis.
AB - The objectives of this study were to develop a standard classification of digital
ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic
studies and to assess the reliability of these definitions as well as of the
measurement of ulcer area. Ten North American rheumatologists with expertise in
SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and
came to a consensus on the definitions for digital, active, healed, and
indeterminate ulcers. These ten raters then examined the right hand of ten SSc
subjects twice and the left hand once to classify ulcers and to measure ulcer
area. Weighted and Fleiss kappa were used to calculate intra- and interrater
agreement on classification of ulcers, and intraclass correlation coefficient
(ICC) was used to assess agreement on ulcer area. Because the traditional ICC
calculations relied on a small number of ulcers, ICCs were recalculated using the
results of linear mixed models to evaluate the variance components of
observations on all the data. Intrarater kappa for classifying DU as not an
ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and
interrater kappa was moderate (0.53). The ICC for ulcer area using the linear
mixed models was moderate both for intrarater (0.57) and interrater (0.48)
measurements. A consensus for the classification of DUs in SSc was developed, and
after a training session, rheumatologists with expertise in SSc are able to
reliably classify DUs and to measure ulcer area.
PMID- 24357323
TI - The Amborella genome and the evolution of flowering plants.
AB - Amborella trichopoda is strongly supported as the single living species of the
sister lineage to all other extant flowering plants, providing a unique reference
for inferring the genome content and structure of the most recent common ancestor
(MRCA) of living angiosperms. Sequencing the Amborella genome, we identified an
ancient genome duplication predating angiosperm diversification, without evidence
of subsequent, lineage-specific genome duplications. Comparisons between
Amborella and other angiosperms facilitated reconstruction of the ancestral
angiosperm gene content and gene order in the MRCA of core eudicots. We identify
new gene families, gene duplications, and floral protein-protein interactions
that first appeared in the ancestral angiosperm. Transposable elements in
Amborella are ancient and highly divergent, with no recent transposon radiations.
Population genomic analysis across Amborella's native range in New Caledonia
reveals a recent genetic bottleneck and geographic structure with conservation
implications.
PMID- 24357326
TI - Outcome and requirement for surgical repair following prenatal diagnosis of
ventricular septal defect.
AB - OBJECTIVE: To document outcome following prenatal diagnosis of ventricular septal
defects (VSDs), particularly associated anomalies and the requirement for
surgical closure of the defect. METHODS: All cases of prenatal diagnosis of a VSD
made by fetal cardiologists at a tertiary fetal medicine referral center in the
period January 2002 to December 2011 were extracted from our database. Data
regarding fetal cardiac diagnosis, extracardiac anomalies, nuchal translucency
thickness and karyotype were noted. RESULTS: A total of 171 cases fulfilled our
selection criteria. Of these, 69% were diagnosed with a perimembranous VSD and
31% with a muscular defect. The median gestational age at diagnosis was 21 + 6
(range, 12 + 0 to 37 + 3) weeks. Owing to severe extracardiac or genetic
conditions, pregnancy resulted in intrauterine death or termination in 49% cases,
and postnatal death occurred in 9% of cases. Seventy-two babies were liveborn,
and were regarded as potential surgical candidates if hemodynamics suggested that
surgery was indicated. Surgical closure of the VSD proved necessary in 50% of the
patients with a perimembranous VSD and 13% of those with a muscular VSD. All
patients operated on survived surgical repair. No karyotypic abnormalities were
identified in fetuses with VSDs that had normal first-trimester screening and no
other sonographic abnormalities. CONCLUSIONS: A high proportion of VSDs diagnosed
during fetal life (29%) require postnatal surgical intervention. The assessment
of hemodynamic significance from fetal echocardiography is imperfect. The
presence of extracardiac abnormalities or abnormal results on first-trimester
screening has a major impact on the incidence of karyotypic abnormalities in
affected fetuses. This should inform discussions with parents about invasive
testing.
PMID- 24357328
TI - Zebrafish ETV7 regulates red blood cell development through the cholesterol
synthesis pathway.
AB - ETV7 is a human oncoprotein that cooperates with EMU-MYC to promote pre-B-cell
leukemia in mice. It is normally expressed in the bone marrow and fetal liver and
is upregulated in primary leukemia, suggesting that it is involved in proper
hematopoiesis and leukemogenesis. ETV7 has been deleted in most rodents, but is
conserved in all other vertebrates, including the zebrafish, Danio rerio. In this
report, we characterize the function of the zebrafish etv7 gene during
erythropoiesis. Our results demonstrate that etv7 regulates the expression of the
zebrafish lanosterol synthase (lss) gene, an essential gene in the cholesterol
synthesis pathway. Furthermore, morpholino knockdown of etv7 leads to loss of
hemoglobin-containing red blood cells, a phenotype that can be rescued by
injection of exogenous cholesterol. We conclude that etv7 is essential for normal
red blood cell development through regulation of the lss gene and the cholesterol
synthesis pathway.
PMID- 24357329
TI - Enhanced energy transfer in quasi-quaternary nanocrystal superlattices.
AB - Quasi-quaternary nanocrystal superlattices are assembled by using exclusively
core-shell particles as building blocks. The assemblies show an enhancement of
energy-transfer from cadmium selenide-based core-shell quantum dots to gold-iron
oxide core-shell nanocrystals compared to random mixtures of the same components.
PMID- 24357327
TI - Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge
(22q11) deletion syndrome.
AB - We assessed feeding-related developmental anomalies in the LgDel mouse model of
chromosome 22q11 deletion syndrome (22q11DS), a common developmental disorder
that frequently includes perinatal dysphagia--debilitating feeding, swallowing
and nutrition difficulties from birth onward--within its phenotypic spectrum.
LgDel pups gain significantly less weight during the first postnatal weeks, and
have several signs of respiratory infections due to food aspiration. Most 22q11
genes are expressed in anlagen of craniofacial and brainstem regions critical for
feeding and swallowing, and diminished expression in LgDel embryos apparently
compromises development of these regions. Palate and jaw anomalies indicate
divergent oro-facial morphogenesis. Altered expression and patterning of
hindbrain transcriptional regulators, especially those related to retinoic acid
(RA) signaling, prefigures these disruptions. Subsequently, gene expression, axon
growth and sensory ganglion formation in the trigeminal (V), glossopharyngeal
(IX) or vagus (X) cranial nerves (CNs) that innervate targets essential for
feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia
anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1.
Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V
phenotype and returns expression levels or pattern of RA-sensitive genes to those
in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not
limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated
anterior-posterior hindbrain differentiation. These disruptions likely contribute
to dysphagia in infants and young children with 22q11DS.
PMID- 24357330
TI - Complex chromosomal rearrangements causing Langer-Giedion syndrome atypical
phenotype: genotype-phenotype correlation and literature review.
AB - Langer-Giedion syndrome (LGS) is caused by a deletion of chromosome 8q23.3
q24.11. The LGS clinical spectrum includes intellectual disability (ID), short
stature, microcephaly, facial dysmorphisms, exostoses. We describe a 4-year-old
girl with ID, short stature, microcephaly, distinctive facial phenotype, skeletal
signs (exostoses on the left fibula, coccyx agenesis, stubby and dysmorphic
sphenoid bone, osteoporosis), central nervous system malformations (hypoplastic
and dysmorphic corpus callosum and septum pellucidum), pituitary gland hypoplasia
and hyperreninemia. Array-CGH revealed complex chromosomal rearrangements. A
diagnosis of LGS was confirmed by the detection of a 8q23.3-q24.1 deletion.
Associated chromosomal abnormalities were a 21q22.1 deletion and a balanced
reciprocal translocation t(2;11)(p24;p15) de novo, confirmed by FISH analysis. We
document the patient's atypical findings, never described in LGS patients, in
order to update the genotype-phenotype correlation. We speculate that the
disruption of regulatory elements mapping upstream CYP11B2 involved in the
deleted region could cause hyperreninemia.
PMID- 24357331
TI - Poly(acrylic acid)-poly(ethylene glycol) nanoparticles designed for ophthalmic
drug delivery.
AB - Poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG), four-arm, amine
terminated particles with nanometer size and spherical shape were obtained by the
polymers cross-linking, via activation with 1-ethyl-3-(3-dimethyl aminopropyl)
carbodiimide hydrochloride, in a w/o emulsion. The morphology and surface charge
of the final particles are strongly dependent on the molar ratio of PAA-PEG and
the PAA concentration. The physicochemical characteristics correlated with the
drug-loading capacity, in vitro and ex vivo release kinetics of pilocarpine
hydrochloride and biocompatibility results indicate that these nanoparticles
exhibit the prerequisite behavior for use as carriers of ophthalmic drugs.
PMID- 24357332
TI - T cell avidity and tumor immunity: problems and solutions.
AB - A potent T cell response is an important component of durable anti-tumor
immunity. The quality of the T cell response can, in-part, be measured by the
avidity of the T cell for its tumor antigen-expressing target. While convention
suggests that raising the avidity of the responding T cells may make for a more
potent anti-tumor immune response, the threshold for effective tumor immunity
remains unclear, as do some of the adverse effects of an inappropriately high
avidity response. In this review, we discuss the relationship between T cell
avidity and anti-tumor immunity, considering both experimental model systems as
well as human clinical trials.
PMID- 24357333
TI - Urantide conformation and interaction with the urotensin-II receptor.
AB - Urotensin II (U-II) is a disulfide bridged peptide hormone identified as the
ligand of a G protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp-c[Cys-Phe
Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor
compound identified to date. We have previously identified the compound termed
urantide (H-Asp-c[Pen-Phe-DTrp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT
receptor (UTR) antagonist described to date. Urantide may have potential clinical
value in the treatment of atherosclerosis. In the present study, we studied the
conformational preferences of urantide in DPC micelles and developed a
urantide/UTR interaction model. This model can help the design of novel peptides
and small molecules as UTR antagonists.
PMID- 24357334
TI - Retinal vasoproliferative tumors in 6 patients with neurofibromatosis type 1.
AB - IMPORTANCE: Retinal vasoproliferative tumors (RVPTs) are an important ocular
finding in patients with neurofibromatosis type 1 (NF1), and early detection of
this association and prompt initiation of treatment may prevent vision loss and
blindness in affected patients. OBJECTIVES: To describe the clinical findings of
RVPTs in patients with NF1 and to underscore the risk of severe vision loss in
such patients. DESIGN, SETTING, AND PATIENTS We performed a retrospective medical
record review of 6 patients with RVPTs and NF1 treated at the Ocular Oncology
Service, Wills Eye Hospital. MAIN OUTCOMES AND MEASURES: The demographics,
clinical features, clinical course, and outcomes of the 6 patients with RVPTs
were recorded. RESULTS Of 275 patients with RVPTs, 6 (2.2%) had NF1. At the time
of diagnosis of RVPT, the median patient age was 12 years (range, 9-36 years).
Visual acuity was variable, ranging from 6/7.5 to light perception on initial
presentation to the oncology service. The RVPT was located between the equator
and ora serrata in all patients. The mean basal tumor diameter was 11 mm, and the
mean tumor thickness was 4 mm. Associated features included subretinal fluid (n =
6), subretinal exudation (n = 6), epiretinal membrane (n = 3), retinal hemorrhage
(n = 2), vitreous hemorrhage (n = 1), retinal neovascularization (n = 1), and
cystoid macular edema (n = 1). Fluorescein angiography revealed early
hyperfluorescence and late staining and leakage of each RVPT. B-scan
ultrasonography revealed acoustic solidity of the lesion. Initial management
included cryotherapy, intravitreal injection of bevacizumab, plaque radiotherapy,
and primary enucleation in 1 patient because of painful neovascular glaucoma.
CONCLUSIONS AND RELEVANCE: We found that RVPTs can develop in patients with NF1
and can cause exudative retinopathy, vitreous hemorrhage, and visual loss.
Patients with NF1 should undergo periodic ophthalmic examination for detection
and treatment of this tumor. It is important to recognize the occurrence of RVPT
in patients with NF1 because knowledge of this association and early treatment
can prevent severe loss of vision in affected patients.
PMID- 24357335
TI - Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in
a patient with behavioral disturbance, autism spectrum disorder, and epilepsy.
AB - We present a patient with a behavioral disorder, epilepsy, and autism spectrum
disorder who has a 520 kb chromosomal deletion at 15q26.1 encompassing three
genes: ST8SIA2, C15orf32, and FAM174B. Alpha-2,8-Sialyltransferase 2 (ST8SIA2) is
expressed in the developing brain and appears to play an important role in
neuronal migration, axon guidance and synaptic plasticity. It has recently been
implicated in a genome wide association study as a potential factor underlying
autism, and has also been implicated in the pathogenesis of bipolar disorder and
schizophrenia. This case provides supportive evidence that ST8SIA2
haploinsufficiency may play a role in neurobehavioral phenotypes.
PMID- 24357336
TI - Re-examination of chewing and spitting behavior: characteristics within and
across eating disorder diagnoses.
AB - Chewing and spitting (CS) out food is a relatively understudied eating disorder
behavior. The aim of this study was to examine lifetime and current frequencies
of CS across eating disorder diagnostic groups and to compare the severity of
eating disorder symptomatology between participants who did and did not endorse
CS. A total of 972 individuals presenting for outpatient eating disorder
treatment between 1985 and 1996 completed a questionnaire that included items
regarding current and lifetime eating disorder behaviors, including CS. Results
indicated that both lifetime and current prevalence estimates of CS varied cross
diagnostically, with CS being more common among those with anorexia nervosa and
bulimia nervosa compared to those with eating disorder not otherwise specified.
CS was significantly associated with several eating disorder symptoms, including
compensatory behaviors, meal restriction, and lower BMI. Those who reported CS
were also younger in age compared to those who did not report CS. These findings
indicate that CS is associated with more severe eating and weight pathology and
is not equally prevalent across eating disorder diagnoses. These results also
support the relatively high occurrence of CS and the importance of targeting this
behavior in eating disorder treatment. Future research should clarify the
correlates, mechanisms, and function of CS in eating disorders.
PMID- 24357337
TI - Safety and efficacy of aprepitant for chemotherapy-induced nausea and vomiting in
pediatric patients: a prospective, observational study.
AB - Pediatric patients between the ages of 12 months and 17 years with a confirmed
malignancy who were scheduled to receive aprepitant as part of triple therapy
antiemetic prophylaxis for a cycle of moderately- or highly emetogenic
chemotherapy were eligible for enrollment. Patients were evaluated for the
incidence of nausea, episodes of emesis, interference with activities of daily
living (ADLs), and appetite through utilization of a patient survey. Eleven
patients were enrolled for a total of 20 patient encounters, mean age 9.55 +/-
4.85 (range, 12 months-17 years). Aprepitant was well-tolerated and complete
response (CR) rate was 38.9%.
PMID- 24357338
TI - p38 and extracellular signal-regulated kinases activations have opposite effects
on primary-cultured rat cerebellar granule neurons exposed to sodium arsenite.
AB - Arsenic is a widespread environmental toxicant in the world and regarded as both
a carcinogen and an anticarcinogen. The present study was designed to evaluate
roles of mitogen-activated protein kinases in sodium arsenite-induced effects on
primary-cultured rat cerebellar granule neurons (CGNs). Results revealed a
decreased viability of the cells exposed to sodium arsenite (from 0 to 50 MUM) in
a dose-dependent manner. Annexin V-fluorescein isothiocyanate assay showed that
apoptosis was obviously induced by arsenite treatment. High phosphorylation
expressions of p38 and extracellular signal-regulated kinases (ERK1/2), but not
of c-Jun N-terminal kinases were observed due to arsenite treatment by western
blotting analysis. Furthermore, SB203580 (an inhibitor of p38) decreased the
percentage of apoptotic cells whereas arsenite-stimulated toxicity was enhanced
by U0126 (an inhibitor of ERK1/2). Taken together, these data suggest that p38
contributes to arsenite-induced apoptosis of rat CGNs, but ERK1/2 may involve in
cell growth and survival.
PMID- 24357339
TI - Use of a pocket-sized ultrasound machine (PUM) for routine examinations in the
third trimester of pregnancy.
AB - OBJECTIVES: To evaluate the application of a pocket-sized ultrasound machine
(PUM) in a routine antenatal third-trimester scan compared with a high
specification ultrasound machine (HSUM). METHODS: This was an observational
cohort study of 53 unselected women who came for their routine third-trimester
ultrasound scan. The first scan was performed by an experienced ultrasonographer
on an HSUM for fetal growth, fetal wellbeing and placental location. A second
experienced operator performed the measurements on the PUM. Both operators were
blinded to the other's findings and measurement results. RESULTS: Fifty-one
patients were eligible and scanned at a median gestational age of 31 + 1 (range,
27 + 2 to 36 + 0) weeks. Mean pregestational body mass index was 22.9 +/- 3.1
(range, 17.6-35.7) kg/m(2) . In the comparison between measurements made using
the PUM and HSUM, perfect agreement was found for fetal position, fetal bladder
and stomach visualization (all kappa 1.0) and very good agreement was found for
placental position (kappa 0.86). Measurements of deepest vertical pocket
correlated moderately (intraclass correlation coefficient (ICC) 0.38 (95% CI,
0.12-0.59); Bland-Altman bias, 2.43 (95% limits of agreement (LoA), -22.65 to
27.51)). For fetal growth measurements there was very good agreement for
biparietal diameter (ICC, 0.93 (95% CI, 0.88-0.96), Bland-Altman bias, -1.06 (95%
LoA, -5.07 to 2.95)), and good agreement for femur length (ICC, 0.66 (95% CI,
0.48-0.79), Bland-Altman bias 0.56 (95% LoA, -5.97 to 7.08)) and transcerebellar
diameter (ICC, 0.65 (95% CI, 0.46-0.78), Bland-Altman bias, -0.84 (95% LoA, -7.77
to 6.09)). CONCLUSION: A battery-driven PUM can be used in third-trimester
obstetrics for routine assessment of fetal growth (biparietal diameter,
transcerebellar diameter and femur length) and for assessment of fetal wellbeing.
PMID- 24357340
TI - Vitamin A and fish oils for retinitis pigmentosa.
AB - BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye
diseases characterized by progressive degeneration of retinal photoreceptors. It
results in severe visual loss that may lead to legal blindness. Symptoms may
become manifest during childhood or adulthood, and include poor night vision
(nyctalopia) and constriction of peripheral vision (visual field loss). This
field loss is progressive and usually does not reduce central vision until late
in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000
patients affected in the USA. At this time, there is no proven therapy for RP.
OBJECTIVES: The objective of this review was to synthesize the best available
evidence regarding the effectiveness and safety of vitamin A and fish oils
(docosahexaenoic acid (DHA)) in preventing the progression of RP. SEARCH METHODS:
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
Register) (2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non
Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August
2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health
Sciences Literature Database (LILACS) (January 1982 to August 2013), the
metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical
Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use
any date or language restrictions in the electronic searches for trials. We last
searched the electronic databases on 20 August 2013. SELECTION CRITERIA: We
included randomized controlled trials (RCTs) evaluating the effectiveness of
vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster
randomized trials and cross-over trials. DATA COLLECTION AND ANALYSIS: We pre
specified the following outcomes: mean change from baseline visual field, mean
change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as
measured by optical coherence tomography (OCT), at one year; as well as mean
change in visual acuity at five-year follow-up. Two authors independently
evaluated risk of bias for all included trials and extracted data from the
publications. We also contacted study investigators for further information on
trials with publications that did not report outcomes on all randomized patients.
MAIN RESULTS: We reviewed 394 titles and abstracts and nine ClinicalTrials.gov
records and included three RCTs that met our eligibility criteria. The three
trials included a total of 866 participants aged four to 55 years with RP of all
forms of genetic predisposition. One trial evaluated the effect of vitamin A
alone, one trial evaluated DHA alone, and a third trial evaluated DHA and vitamin
A versus vitamin A alone. None of the RCTs had protocols available, so selective
reporting bias was unclear for all. In addition, one trial did not specify the
method for random sequence generation, so there was an unclear risk of bias. All
three trials were graded as low risk of bias for all other domains. We did not
perform meta-analysis due to clinical heterogeneity of participants and
interventions across the included trials.The primary outcome, mean change of
visual field from baseline at one year, was not reported in any of the studies.
No toxicity or adverse events were reported in these three trials. No trial
reported a statistically significant benefit of vitamin supplementation on the
progression of visual field loss or visual acuity loss. Two of the three trials
reported statistically significant differences in ERG amplitudes among some
subgroups of participants, but these results have not been replicated or
substantiated by findings in any of the other trials. AUTHORS' CONCLUSIONS: Based
on the results of three RCTs, there is no clear evidence for benefit of treatment
with vitamin A and/or DHA for people with RP, in terms of the mean change in
visual field and ERG amplitudes at one year and the mean change in visual acuity
at five years follow-up. In future RCTs, since some of the studies in this review
included unplanned subgroup analysis that suggested differential effects based on
previous vitamin A exposure, investigators should consider examining this issue.
Future trials should take into account the changes observed in ERG amplitudes and
other outcome measures from trials included in this review, in addition to
previous cohort studies, when calculating sample sizes to assure adequate power
to detect clinically and statistically meaningful difference between treatment
arms.
PMID- 24357341
TI - Thricho-rhino-phalangeal syndrome and severe osteoporosis: a rare association or
a feature? An effective therapeutic approach with biphosphonates.
AB - Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation
syndrome characterized by hair, craniofacial and skeletal abnormalities, skin
laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias.
Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on
chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1
genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals,
and severe short stature, but without exostoses. We present the case of a 7-year
old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone
fractures, an association described only once in the literature, successfully
treated with biphosphonates. Bone mineral density (BMD) at dual-energy X-ray
Absorptiometry (DXA) was of 0.331 g/cm(2) at lumbar spine with. He had four
spontaneous femoral fractures in a year, and for this reason he was been operated
for positioning intramedullary osteosynthesis and orthopedic supports. Due to the
severity of the clinical and radiological pattern it was established, after
approval of the Ethical Committee, to begin off-label therapy with infusions of
neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this
patient, effective both in terms of clinical (absence of new fractures) and
mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that
treatment with biphosponates can be taken in account as a possible therapeutic
option in case of bone fragility in patients with TRPSI.
PMID- 24357342
TI - Multidrug-resistant endemic clonal strain of Candida auris in India.
AB - Candida auris is a recently described rare agent of fungemia. It is notable for
its antifungal resistance. A total of 15 C. auris isolates, originating from
seven cases of fungemia, three cases of diabetic gangrenous foot, and one case of
bronchopneumonia from a tertiary care hospital in south India, were investigated.
All of the 15 isolates were identified by sequencing and 14 of these along with
12 C. auris isolates previously reported from two hospitals in Delhi, north
India, two each from Japan and Korea were genotyped by amplified fragment length
polymorphism (AFLP). In vitro antifungal susceptibility testing (AFST) was done
by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution
method. Candida auris isolates were misidentified as Candida haemulonii by VITEK.
All were resistant to fluconazole [geometric mean minimum inhibitory
concentration (MIC) 64 MUg/ml] and 11 isolates were resistant to voriconazole
(MIC >=1 MUg/ml). Forty-seven percent of the C. auris isolates were resistant to
flucytosine (MIC >=64 MUg/ml) and 40% had high MIC (>=1 MUg/ml) of caspofungin.
Breakthrough fungemia developed in 28.6% of patients and therapeutic failure in 4
(66.7%) patients. Interestingly, the 26 Indian C. auris isolates from north and
south India were clonal and phenotypically and genotypically distinct from Korean
and Japanese isolates. The present study demonstrates that C. auris is a
potential emerging pathogen that can cause a wide spectrum of human mycotic
infections. The prevalence of a C. auris endemic clonal strain resistant to
azoles and other antifungals in Indian hospitals with high rates of therapeutic
failure in cases of fungemia is worrisome.
PMID- 24357343
TI - Interstitial deletion of 2q24.2: further delineation of an emerging syndrome
associated with intellectual disability, severe hypotonia and moderate
intrauterine growth restriction.
PMID- 24357344
TI - Outcome of adverse events and medical errors in the intensive care unit: a
systematic review and meta-analysis.
AB - Adverse events and medical errors (AEs/MEs) are more likely to occur in the
intensive care unit (ICU). Information about the incidence and outcomes of such
events is conflicting. A systematic review and meta-analysis were conducted to
examine the effects of MEs/AEs on mortality and hospital and ICU lengths of stay
among ICU patients. Potentially eligible studies were identified from 4 major
databases. Of 902 studies screened, 12 met the inclusion criteria, 10 of which
are included in the quantitative analysis. Patients with 1 or more MEs/AEs (vs no
MEs/AEs) had a nonsignificant increase in mortality (odds ratio = 1.5; 95%
confidence interval [CI] = 0.98-2.14) but significantly longer hospital and ICU
stays; the mean difference (95% CI) was 8.9 (3.3-14.7) days for hospital stay and
6.8 (0.2-13.4) days for ICU. The ICU environment is associated with a substantial
incidence of MEs/AEs, and patients with MEs/AEs have worse outcomes than those
with no MEs/AEs.
PMID- 24357345
TI - Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular
endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast
tumor model.
AB - Angiogenesis has been known to increase tumor growth and for its metastatic
potential in human tumors. Vascular endothelial growth factor (VEGF) plays an
important role in tumor angiogenesis and is a promising therapeutic target for
breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast
cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits
tumor growth and migration in rats. The purpose of the present study was to
improve therapeutic efficacy in breast cancer with the codelivery of siRNA
expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into
chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids
greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro
study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene
silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study
breast tumor model demonstrated that the administration of coencapsulation of
psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor
growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone.
These results indicate that chitosan NPs can be effectively used for the
codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy
against breast cancer.
PMID- 24357346
TI - Mediterranean diet and type 2 diabetes.
AB - Consumption of selected dietary components is favourably associated with
prevention of type 2 diabetes, but discordant results for some foods or single
nutrients continue to appear. The study of complete dietary patterns represents
the most adequate approach to assess the role of diet on the risk of diabetes.
The term 'Mediterranean diet' essentially refers to a primarily plant-based
dietary pattern whose greater consumption has been associated with higher
survival for lower all-cause mortality. At least five large prospective studies
report a substantially lower risk of type 2 diabetes in healthy people or at risk
patients with the highest adherence to a Mediterranean diet. Five randomized
controlled trials have evaluated the effects of a Mediterranean diet, as compared
with other commonly used diets, on glycaemic control in subjects with type 2
diabetes. Improvement of HbA1c levels was greater with a Mediterranean diet and
ranged from 0.1% to 0.6% for HbA1c . No trial reported worsening of glycaemic
control with a Mediterranean diet. Although no controlled trial specifically
assessed the role of a Mediterranean diet in reducing cardiovascular events in
type 2 diabetes, there is evidence that post-infarct or high-risk patients,
including diabetic patients, may have cardiovascular benefits from a
Mediterranean diet. The evidence so far accumulated suggests that adopting a
Mediterranean diet may help prevent type 2 diabetes; moreover, a lower
carbohydrate, Mediterranean-style diet seems good for HbA1c reduction in persons
with established diabetes.
PMID- 24357347
TI - A systematic exploration of high-temperature stress-responsive genes in potato
using large-scale yeast functional screening.
AB - Potato (S. tuberosum) is a highly heat-sensitive crop; a slight rise from optimal
temperature can lead to drastic decline in tuber yield. Despite several
advancements made in breeding for thermo-tolerant potato, molecular mechanisms
governing thermo-tolerance is poorly understood. The first step towards
understanding the thermo-tolerance mechanism is to identify the key genes
involved in it. Here we used a yeast-based functional screening method to
identify, characterize and classify potato genes with potentials to impart heat
tolerance. We constructed two cDNA expression libraries from heat-stressed potato
plants (35 degrees C) after 2 and 48 h of treatment. 95 potential candidate
genes were identified based on enhanced ability of yeast cells over-expressing
heterologous potato cDNA sequences to tolerate heat stress. Cross-resistance
analysis of these heat-tolerant yeast clones to other abiotic stresses indicated
that 20 genes were responsive to drought, 14 to salt and 11 to heat/drought/salt
stresses. Comparison of 95 genes with reported whole potato transcriptome data
showed that majority of them have varying expression patterns under heat, drought
and salt stresses. The expression pattern was validated by analyzing the
expression of 22 randomly selected genes under various stresses using qPCR. Gene
ontology (GO) enrichment analysis of these 95 genes indicated that most of them
are involved in various cellular metabolism, signal transduction, response to
stress and protein folding, suggesting possible role of these genes in heat
tolerance of potato. Genes identified from this study can be potential candidates
for engineering heat tolerance as well as broad-spectrum abiotic stress tolerance
of potato.
PMID- 24357348
TI - Useful tests for hepatic encephalopathy in clinical practice.
AB - Hepatic encephalopathy (HE) is a serious complication of liver disease and
portosystemic shunting that represents a continuum of neuropsychiatric changes
and altered consciousness. It is classified as overt HE (OHE) when clinically
apparent or as covert HE (CHE) in its mildest form. Progression of CHE to OHE and
its impact of quality of life make its early diagnosis imperative. Several
diagnostic techniques ranging from simple clinical scales to sophisticated
computerized tests exist, yet diagnosis remains a challenge, due to the time,
cost, and personnel involved. Psychometric tests appear promising due to their
high sensitivity and low cost, but results are variable depending on age and
education. The pros and cons of current diagnostic methods for OHE and CHE are
reviewed, along with strategy for CHE testing.
PMID- 24357349
TI - Update on ablation for Barrett's esophagus.
AB - Endoscopic ablation has dramatically changed the treatment algorithm for patients
with Barrett's esophagus. Studies clearly show the benefits of this approach for
patients with high-grade dysplasia and intramucosal carcinoma. Recent studies
also provide evidence in support of this approach for patients with low-grade
dysplasia but not for patients with nondysplastic Barrett's epithelium.
Endoscopic ablation is safe and efficacious in most but not all patients and
disease progression may occur during initial therapy as well as after successful
completion in a small difficult to identify subset of patients. Furthermore, the
past year has provided us with a better understanding of the durability of
endoscopic ablation with highly variable rates of disease recurrence. Studies are
underway to help determine predictors of response and recurrence.
PMID- 24357350
TI - Dietary fructose intolerance, fructan intolerance and FODMAPs.
AB - Dietary intolerances to fructose, fructans and FODMAPs (fermentable
oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet
poorly recognized and managed. Over the last decade, they have come to the
forefront because of new knowledge on the mechanisms and treatment of these
conditions. Patients with these problems often present with unexplained bloating,
belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined
the most up-to-date research on these food-related intolerances, discussed
controversies, and have provided some guidelines for the dietary management of
these conditions. Breath testing for carbohydrate intolerance appears to be
standardized and essential for the diagnosis and management of these conditions,
especially in the Western population. While current research shows that the
FODMAP diet may be effective in treating some patients with irritable bowel
syndrome, additional research is needed to identify more foods items that are
high in FODMAPs, and to assess the long-term efficacy and safety of dietary
interventions.
PMID- 24357351
TI - A tetramethylpyrazine piperazine derivate CXC137 prevents cell injury in SH-SY5Y
cells and improves memory dysfunction of rats with vascular Dementia.
AB - We investigated the effects of CXC137, a tetramethylpyrazine piperazine derivate,
on cell damage induced by N-methyl-D-aspartate (NMDA) in human derived
neuroblastoma cells (SH-SY5Y) and its effect on memory dysfunction of rats with
vascular dementia. It was found that the presence of CXC137 increased SH-SY5Y
cells viability by inhibition of cell apoptosis induced by NMDA. These effects of
CXC137 were accompanied by increases of the antioxidant superoxide dismutase
activity and the level of reduced glutathione, and a decrease of lipid
peroxidation product, malondialdehyde. The presence of CXC137 also showed to
produce strong inhibition of cellular lactate dehydrogenase leakage, cell
apoptosis and intracellular calcium overload. In a vascular dementia rat model
established by bilateral common carotid arteries occlusion, treatment with CXC137
from 2 to 35 day of post-operation significantly improves the motor performance,
spatial learning and memory capability of rats in both the prehensile traction
test and Morris water maze test, an effect that was companied by reductions of
the animal glutamic acid levels and the degree of brain mitochondrial swelling.
These results suggest that CXC137 can improve the memory dysfunction in dementia
and thus has important therapeutic potential for the treatment of dementia.
PMID- 24357352
TI - Immunomodulatory function of kappa-carrageenan oligosaccharides acting on LPS
activated microglial cells.
AB - The major neurodegenerative diseases are characterized by increasing of activated
microglial cells and inflammatory cytokines in the central nervous system.
Carrageenan extracted from red algae is a kind of polysaccharide with sulfate
groups. The oligosaccharides were obtained from carrageenan by enzymatic
degradation. To detect the immunomodulatory activity of kappa-carrageenan
oligosaccharides (KOS) on microglial cells and the relationship to the sulfate
group content, the desulfated derivatives of KOS (DSK) were obtained by dimethyl
sulfoxide-methanol-pyridine method. KOS was labeled with fluorescein
isothiocyanate. The effect of KOS and DSK on lipopolysaccharide (LPS)-activated
microglial cells was detected. Hematoxylin-eosin staining and flow cytometric
were used to detect the cell viability. The "scratch" migration assay, ornithine
analysis and RT-PCR were used to determine the cell migration, arginase and TNF
alpha released by microglial cells, respectively. The effect of LPS and KOS on
microglial cells was determined by flow cytometry and laser scanning confocal
microscopy. The results showed that KOS and DSK could inhibit the cell viability,
arginase and TNF-alpha released by LPS-activated microglia cell with
concentration dependent manner. But the effect of DSK was weaker than that of
KOS. KOS aggregated on the cell surface firstly, and then they enter into the
cell to the nucleus, spread over the entire cell finally. But the exist of LPS
could prevent the entrance of KOS. It could be concluded that KOS could protect
microglial cells from being activated by LPS, and its inhibition function had
relationship to the sulfate group content of KOS, while there were competition
between LPS and KOS.
PMID- 24357353
TI - A mildly inducible and selective cross-link methodology for RNA duplexes.
AB - We here report on the furan oxidation methodology for interstrand cross-linking
of RNA duplexes, which have a different structure and are more stiff, reactive
and labile than their DNA counterparts. Through this mildly inducible approach,
natural unmodified RNA can be selectively cross-linked in high yield. The method
therefore has direct applications in the increasing number of RNA based
technologies.
PMID- 24357354
TI - Evaluation of the surgical anatomy of sphenoid ostium with 3D computed
tomography.
AB - PURPOSE: To evaluate the anatomy of the sphenoid ostium (SO), which has so far
only been investigated with the aid of two-dimensional computed tomography (CT)
or using a cadaver, from a new point of view through the use of 3D CT for the
first time. METHODS: We have evaluated 50 patients who had CT angiography done
for different reasons. The sphenoid sinus types and the SO were evaluated three
dimensionally. The average diameters of the sphenoid ostia, and their distances
to the midline, as well as to each other and the choana have been measured. In
addition, the SO were categorized according to their shapes. RESULTS: The average
age of the patients was 48.5. No SO was found in seven cases (14 %). The average
distance of the SO to the midline was 2.78 mm on the right side and 2.77 on the
left. Four different shapes of SO were determined; round, oval, irregular and
linear. The average distance of the right and left SO to the choana was 15.22 +/-
0.95 and 14.87 +/- 1.11 mm, respectively. No statistically significant difference
was found between the male and female sexes with regard to the calculated
diameters and shapes of the SO (p > 0.05). CONCLUSION: The anatomy of the
sphenoid sinus and the SO varies widely from individual to individual. We have
demonstrated in our study that these anatomic variations could be evaluated pre
operatively. Using this imaging technique, surgeons can make a pre-operative 3D
evaluation of the sphenoid ostium, encountered in the surgery and thus achieve
better orientation.
PMID- 24357355
TI - Biophysical aspects of cyclodextrin interaction with paraoxon.
AB - Cyclodextrins are torus-shaped polymers of glucose that can bind
organophosphorous compounds such as nerve agents and pesticides. We demonstrate
here that cyclodextrin can bind up to two paraoxon molecules with a K(av) of 6775
M(-1). Molecular modeling shows that the paraoxon appears to bind in polar
opposite orientation and have an average binding energy of -89 Kcals/mol.
Published 2013. This article is a U.S. Government work and is in the public
domain in the USA.
PMID- 24357356
TI - Conventional specimen preparation techniques for transmission electron microscopy
of cultured cells.
AB - In this chapter, we discuss conventional methods for handling cells grown
suspended in liquid culture and on solid substrates. Protocols are given on how
to prepare cultures for transmission electron microscopy, including the most
commonly used buffers, fixatives, enrobement media, and embedding resins. These
methods are suitable for a wide variety of organisms, ranging from prokaryotic
bacteria to mammalian cells.
PMID- 24357357
TI - Microwave-assisted processing and embedding for transmission electron microscopy.
AB - Microwave processors can provide a means of rapid processing and resin embedding
for biological specimens that are to be sectioned and examined by transmission
electron microscopy. This chapter describes a microwave-assisted protocol for
processing, dehydrating and embedding biological material, taking them from
living specimens to blocks embedded in sectionable resin in 4 h or less.
PMID- 24357358
TI - Processing plant tissues for ultrastructural study.
AB - This chapter briefly describes conventional and microwave-assisted chemical
fixation methods, as well as cryo-specimen preparation techniques for studying
the cellular and organelle ultrastructure of plant tissues under transmission
electron microscopy. The general methods and procedures for the plant specimen
preparation (including fixation, dehydration, resin infiltration, and embedding)
are similar to those for animal tissues. However, certain special characteristic
features of plant tissues such as thick cellulosic cell wall, waxy substance in
the cuticle, large amount of gases in the intercellular spaces, and the presence
of vacuoles have created fixation and resin filtration difficulties. Specific
modifications of the protocols used for animal tissues are therefore required,
such as the application of vacuum during the initial fixation and resin
infiltration stage to remove gases from the tissues and resin. Microwave-assisted
procedure can reduce specimen preparation time, but both conventional and
microwave-assisted chemical fixation procedures produce artifacts. Cryo-specimen
preparation involves with high-pressure freezing and freeze-substitution can
minimize artifact formation, but their application to highly vacuolated, thick
walled plant cells is limited.
PMID- 24357359
TI - Staining sectioned biological specimens for transmission electron microscopy:
conventional and en bloc stains.
AB - Post-staining of ultrathin sections and/or en bloc staining of specimens is
necessary for differential contrast and improved resolution of cellular
structures. Often specimens are fixed and stained with osmium tetroxide during
fixation, but additional contrast is the result of additional heavy metal stains
on the sections. The most common post-staining of sections is done on grids by
aqueous uranyl acetate followed by lead citrate. When it is apparent that simple,
aqueous uranium and lead post-staining is not adequate, other stains are invoked.
These procedures can be as simple as en bloc staining with uranyl acetate after
primary fixation and osmication. Over the years, several other treatments have
been developed for use with the primary fixation or during dehydration. Tannic
acid, paraphenylenediamine (PPD), and malachite green can all serve as en bloc
stains and can contribute to overall improved visualization of ultrastructural
details in biological specimens. Tannic acid and PPD improve membrane
preservation, and malachite green is a phospholipid stain. All of these stains
are compatible with aqueous fixatives and should be considered when the usual
stains are not satisfactory. Marinozzi rings and microwave-assisted post-staining
offer alternatives to traditional grid staining. In addition, stain precipitates
on grids often can be removed by treatment with 10 % (v/v) acetic acid.
PMID- 24357360
TI - Metal shadowing for electron microscopy.
AB - Metal shadowing of bacteria, viruses, isolated molecules, and macromolecular
assemblies is another high-resolution method for observing the ultrastructure of
biological specimens. The actual procedure for producing a metal shadow is
relatively simple; a heavy metal is evaporated from a source at an oblique angle
to the specimen. The metal atoms pile up on the surfaces that face the source,
but the surfaces away from the source are shielded and receive little metal
deposit, creating a "shadow." However, the process of producing biological
specimens that are suitable for metal shadowing can be very complex. There are a
whole host of specimen preparation techniques that can precede metal shadowing,
and all provide superior preservation in comparison to air drying, a required
step in negative staining procedures. The physical forces present during air
drying (i.e., surface tension of the water-air interface) will literally crush
most biological specimens as they dry. In this chapter I explain the development
of and procedures for the production of biological specimens from macromolecular
assemblies (e.g., DNA and RNA), purified isolated molecules (e.g., proteins), and
isolated viruses and bacteria preparations suitable for metal shadowing. A
variation on this basic technique is to rotate the specimen during the metal
deposition to produce a high-resolution three-dimensional rendering of the
specimen.
PMID- 24357361
TI - Freeze fracture and freeze etching.
AB - Freeze fracture depends on the property of frozen tissues or cells, when cracked
open, to split along the hydrophobic interior of membranes, thus revealing broad
panoramas of membrane interior. These large panoramas reveal the three
dimensional contours of membranes making the methods well suited to studying
changes in membrane architecture. Freshly split membrane faces are visualized by
platinum or tungsten shadowing and carbon backing to form a replica that is then
cleaned of tissue and imaged by TEM. Etching, i.e., removal of ice from the
frozen fractured specimen by sublimation prior to shadowing, can also reveal the
true surfaces of the membrane as well as the extracellular matrix and
cytoskeletal networks that contact the membranes. Since the resolution of detail
in the metal replicas formed is 1-2 nm, these methods can also be used to
visualize macromolecules or macromolecular assemblies either in situ or displayed
on a mica surface. These methods are available for either specimens that have
been chemically fixed or specimens that have been rapidly frozen without chemical
intervention.
PMID- 24357362
TI - Conventional specimen preparation techniques for scanning electron microscopy of
biological specimens.
AB - In this chapter, methods are described for preparing biological specimens for
examination in the scanning electron microscope. Conventional procedures are
described for handling cells grown in liquid culture as well as on substrates
such as culture dishes, slide culture chambers, or agar. These protocols may be
used to process not only cultured organisms but also larger botanical and
zoological specimens.
PMID- 24357363
TI - High-pressure freezing: current state and future prospects.
AB - In this chapter we discuss the latest developments in the field of high-pressure
freezing (HPF). The Leica HPF machine EM HPM100 is discussed in detail due to
significant changes compared to its predecessor model. Its centerpiece is a
multipart polymer cartridge which holds the specimen carrier sandwich and guides
it automatically through the freezing process until immersed in liquid nitrogen.
The cartridge can be adapted to the specimen and carrier geometry to optimize the
flow of liquid nitrogen and hence rapid cooling. Dedicated cartridges are
available for a variety of different carriers, including carriers for samples of
up to 5 mm in diameter. Cartridge-specific handling and carrier assemblies are
described extensively for freezing samples in aluminum specimen carriers, cell
cultures grown on Sapphire discs, suspensions for freeze-fracturing, and
specimens for cryo-sectioning. Additionally, we include an advanced technique to
freeze monolayer cell cultures on Sapphire discs with the Leica EM PACT2 HPF
machine using a composite carrier.
PMID- 24357364
TI - Cryo-fixation by self-pressurized rapid freezing.
AB - High-pressure freeze fixation is the method of choice to arrest instantly all
dynamic and physiological processes inside cells, tissues, and small organisms.
Embedded in vitreous ice, such samples can be further processed by freeze
substitution or directly analyzed in their fully hydrated state by cryo-electron
microscopy of vitreous sections (CEMOVIS) to explore cellular ultrastructure as
close as possible to the native state. Here, we describe the procedure of self
pressurized rapid freezing as fast, easy-to-use, and low-cost freeze fixation
method, avoiding the usage of a high-pressure freezing (HPF) apparatus. Cells or
small organisms are placed in capillary metal tubes, which are tightly closed and
plunged directly into liquid ethane cooled by liquid nitrogen. In parts of the
tube, crystalline ice is formed and builds up pressure sufficient for the liquid
glass transition of the remaining specimen. The quality of samples is equivalent
to preparations by conventional HPF apparatus, allowing for high-resolution cryo
EM applications or for freeze substitution and plastic embedding.
PMID- 24357365
TI - Cryo-electron microscopy of vitreous sections.
AB - More than 30 years ago two groups independently reported the vitrification of
pure water, which was until then regarded as impossible without a cryoprotectant
[1, 2]. This opened the opportunity to cryo-electron microscopy (cryo-EM) to
observe biological samples at nanometer scale, close to their native state.
However, poor electron penetration through biological samples sets the limit for
sample thickness to less than the average size of the mammalian cell. In order to
image bulky specimens at the cell or tissue level in transmission electron
microscopy (TEM), a sample has to be either thinned by focused ion beam or
mechanically sectioned. The latter technique, Cryo-Electron Microscopy of
Vitreous Section (CEMOVIS), employs cryo-ultramicrotomy to produce sections with
thicknesses of 40-100 MUm of vitreous biological material suitable for cryo-EM.
CEMOVIS consists of trimming and sectioning a sample with a diamond knife,
placing and attaching the section onto an electron microscopy grid, transferring
the grid to the cryo-electron microscope and imaging. All steps must be carried
on below devitrification temperature to obtain successful results. In this
chapter we provide a step-by-step guide to produce and image vitreous sections of
a biological sample.
PMID- 24357366
TI - Negative staining and cryo-negative staining: applications in biology and
medicine.
AB - Negative staining is widely applicable to isolated viruses, protein molecules,
macromolecular assemblies and fibrils, subcellular membrane fractions, liposomes
and artificial membranes, synthetic DNA arrays, and also to polymer solutions and
a variety of nanotechnology samples. Techniques are provided for the preparation
of the necessary support films (continuous carbon and holey/perforated carbon).
The range of suitable negative stains is presented, with some emphasis on the
benefit of using ammonium molybdate and of negative stain-trehalose combinations.
Protocols are provided for the single droplet negative staining technique (on
continuous and holey carbon support films), the floating and carbon sandwich
techniques in addition to the negative staining-carbon film (NS-CF) technique for
randomly dispersed fragile molecules, 2D crystallization of proteins and for
cleavage of cells and organelles. Immuno-negative staining and negative staining
of affinity labeled complexes (e.g., biotin-streptavidin) are presented in some
detail. The formation of immune complexes in solution for droplet negative
staining is given, as is the use of carbon-plastic support films as an adsorption
surface on which to perform immunolabeling or affinity experiments, prior to
negative staining. Dynamic biological systems can be investigated by negative
staining, where the time period is in excess of a few minutes, but there are
possibilities to greatly reduce the time by rapid stabilization of molecular
systems with uranyl acetate or tannic acid. The more recently developed cryo
negative staining procedures are also included: first, the high concentration
ammonium molybdate procedure on holey carbon films and second, the carbon
sandwich procedure using uranyl formate. Several electron micrographs showing
examples of applications of negative staining techniques are included and the
chapter is thoroughly referenced.
PMID- 24357367
TI - Electron microscopy of microtubule cytoskeleton assembly in vitro.
AB - Cell-free cytoplasm isolated from meiotic Xenopus egg extracts reconstitutes
microtubule phenomena in vitro. These crude extracts assemble bipolar meiotic
spindles and are readily fractionated for biochemical assays, providing a good
tool to dissect molecular mechanism. We developed techniques for immunoelectron
microscopy of microtubule structures assembled in perfusion chambers and in
solution.
PMID- 24357368
TI - Cryosectioning fixed and cryoprotected biological material for
immunocytochemistry.
AB - Immunocytochemistry for electron microscopy provides important information on the
location and relative abundance of proteins inside cells. Gaining access to this
information without extracting or disrupting the location of target proteins
requires specialized preparation methods. Sectioning frozen blocks of chemically
fixed and cryoprotected biological material is one method for obtaining
immunocytochemical data. Once the cells or tissues are cut, the cryosections are
thawed, mounted onto coated grids, and labeled with specific antibodies and
colloidal gold probes. They are then embedded in a thin film of plastic
containing a contrasting agent. Subcellular morphology can then be correlated
with specific affinity labeling by examination in the transmission electron
microscope (TEM). The major advantage of using thawed cryosections for
immunolabeling is that the sections remain fully hydrated through the
immunolabeling steps, reducing the possibility of dehydration-induced antigen
modification. Modern technical advancements both in preparation protocols and
equipment design make cryosectioning a routine and rapid approach for
immunocytochemistry that may provide increased sensitivity for some antibodies.
PMID- 24357369
TI - Analysis of specificity in immunoelectron microscopy.
AB - Immunoelectron microscopy (immuno-EM) using gold labeling on sections is a
powerful technique for mapping the distribution of proteins, lipids,
carbohydrates, and nucleic acids in intact biological systems. The gold particles
comprise a useful and readily quantifiable digital readout. Simply applying a
labeling reagent (antibody or other affinity probe) to an ultrathin section
yields a pattern of gold signal over the biological structures displayed in the
section. This initial (raw) distribution of gold signal contains both specific
and nonspecific labeling. Here we describe a method for removing nonspecific
labeling to leave the target-specific signal. This specific labeling distribution
better reflects the "real" distribution of the cell component of interest.
PMID- 24357370
TI - Cryo-electron microscopy of membrane proteins.
AB - Electron crystallography is used to study membrane proteins in the form of
planar, two-dimensional (2D) crystals, or other crystalline arrays such as
tubular crystals. This method has been used to determine the atomic resolution
structures of bacteriorhodopsin, tubulin, aquaporins, and several other membrane
proteins. In addition, a large number of membrane protein structures were studied
at a slightly lower resolution, whereby at least secondary structure motifs could
be identified.In order to conserve the structural details of delicate crystalline
arrays, cryo-electron microscopy (cryo-EM) allows imaging and/or electron
diffraction of membrane proteins in their close-to-native state within a lipid
bilayer membrane.To achieve ultimate high-resolution structural information of 2D
crystals, meticulous sample preparation for electron crystallography is of
outmost importance. Beam-induced specimen drift and lack of specimen flatness can
severely affect the attainable resolution of images for tilted samples. Sample
preparations that sandwich the 2D crystals between symmetrical carbon films
reduce the beam-induced specimen drift, and the flatness of the preparations can
be optimized by the choice of the grid material and the preparation protocol.Data
collection in the cryo-electron microscope using either the imaging or the
electron diffraction mode has to be performed applying low-dose procedures. Spot
scanning further reduces the effects of beam-induced drift. Data collection using
automated acquisition schemes, along with improved and user-friendlier data
processing software, is increasingly being used and is likely to bring the
technique to a wider user base.
PMID- 24357371
TI - Tracking DNA and RNA sequences at high resolution.
AB - In this chapter, the basic principles and protocols of the electron microscopical
detections of specific DNA and RNA sequences are described. We focused primarily
on a comparison of various methods of electron microscopy in situ hybridization
(EM-ISH) with respect to their sensitivity and the structural preservation of the
sample with the aim of helping the readers select the appropriate hybridization
protocol. As the post-embedding EM-ISH most frequently represents the optimal
choice, the protocol for the post-embedding EM-ISH approach is described in
detail. Concurrently, the alternative methods based on the enzymatic synthesis of
the labeled nucleic acids chains that can be used for the detection of DNA or RNA
molecules in situ are mentioned. In this respect, the technique enabling the
enzymatic detection of the polyadenylated RNA sequences is described in detail.
PMID- 24357373
TI - Biological applications of phase-contrast electron microscopy.
AB - Here, I review the principles and applications of phase-contrast electron
microscopy using phase plates. First, I develop the principle of phase contrast
based on a minimal model of microscopy, introducing a double Fourier-transform
process to mathematically formulate the image formation. Next, I explain four
phase-contrast (PC) schemes, defocus PC, Zernike PC, Hilbert differential
contrast, and schlieren optics, as image-filtering processes in the context of
the minimal model, with particular emphases on the Zernike PC and corresponding
Zernike phase plates. Finally, I review applications of Zernike PC cryo-electron
microscopy to biological systems such as protein molecules, virus particles, and
cells, including single-particle analysis to delineate three-dimensional (3D)
structures of protein and virus particles and cryo-electron tomography to
reconstruct 3D images of complex protein systems and cells.
PMID- 24357372
TI - Visualization of DNA and protein-DNA complexes with atomic force microscopy.
AB - This article describes sample preparation techniques for AFM imaging of DNA and
protein-DNA complexes. The approach is based on chemical functionalization of the
mica surface with aminopropyl silatrane (APS) to yield an APS-mica surface. This
surface binds nucleic acids and nucleoprotein complexes in a wide range of ionic
strengths, in the absence of divalent cations, and in a broad range of pH. The
chapter describes the methodologies for the preparation of APS-mica surfaces and
the preparation of samples for AFM imaging. The protocol for synthesis and
purification of APS is also provided. The AFM applications are illustrated with
examples of images of DNA and protein-DNA complexes.
PMID- 24357375
TI - Electron tomography for organelles, cells, and tissues.
AB - Electron tomography (ET) is an emerging electron microscopy (EM) technique for
three-dimensional (3D) visualization of molecular arrangements and
ultrastructural architectures in organelles, cells, and tissues at 2-10 nm
resolution. The 3D tomogram is reconstructed from a series of 2D EM images taken
from a single specimen at different projecting orientations. The specimen for ET
must be specially prepared to meet the ET imaging requirements, i.e.,
ultrastructural preservation, specimen thickness, tolerance of electron dose and
vacuum, and image contrast. In this chapter, the strategies of specimen
preparation of organelles, cells, and tissues and the corresponding EM imaging
requirements for ET will be described in detail. In addition, the general
procedures tomographic reconstruction and tomogram interpretation will be
described.
PMID- 24357376
TI - Correlative light and electron microscopy: from live cell dynamic to 3D
ultrastructure.
AB - Correlative light and electron microscopy (CLEM) aims at combining data acquired
from the same sample through both imaging modalities. Many combinations can be
found in the literature where almost any kind of light microscopy (LM) has been
associated to different processing in electron microscopy (EM) and applied to a
wide variety of specimen, from cultured cells to multicellular organisms. In this
chapter, we focus on a technique that intends to combine LM acquisition on living
cells with transmission EM (TEM) analysis. A specific attention is given to the
description of a method to bring precise coordinates to the object of interest,
to allow a straightforward correlation between LM and EM. Moreover, we describe
how, by using high-pressure freezing as a fixation technique, dynamic events
observed at the LM are captured and studied at the ultrastructural level.
PMID- 24357374
TI - Single particle cryo-electron microscopy and 3-D reconstruction of viruses.
AB - With fast progresses in instrumentation, image processing algorithms, and
computational resources, single particle electron cryo-microscopy (cryo-EM) 3-D
reconstruction of icosahedral viruses has now reached near-atomic resolutions (3
4 A). With comparable resolutions and more predictable outcomes, cryo-EM is now
considered a preferred method over X-ray crystallography for determination of
atomic structure of icosahedral viruses. At near-atomic resolutions, all-atom
models or backbone models can be reliably built that allow residue level
understanding of viral assembly and conformational changes among different stages
of viral life cycle. With the developments of asymmetric reconstruction, it is
now possible to visualize the complete structure of a complex virus with not only
its icosahedral shell but also its multiple non-icosahedral structural features.
In this chapter, we will describe single particle cryo-EM experimental and
computational procedures for both near-atomic resolution reconstruction of
icosahedral viruses and asymmetric reconstruction of viruses with both
icosahedral and non-icosahedral structure components. Procedures for rigorous
validation of the reconstructions and resolution evaluations using truly
independent de novo initial models and refinements are also introduced.
PMID- 24357377
TI - Nanometer-resolution fluorescence electron microscopy (nano-EM) in cultured
cells.
AB - Nano-resolution fluorescence electron microscopy (nano-fEM) pinpoints the
location of individual proteins in electron micrographs. Plastic sections are
first imaged using a super-resolution fluorescence microscope and then imaged on
an electron microscope. The two images are superimposed to correlate the position
of labeled proteins relative to subcellular structures. Here, we describe the
method in detail and present five technical advancements: the use of uranyl
acetate during the freeze-substitution to enhance the contrast of tissues and
reduce the loss of fluorescence, the use of ground-state depletion instead of
photoactivation for temporal control of fluorescence, the use of organic
fluorophores instead of fluorescent proteins to obtain brighter fluorescence
signals, the use of tissue culture cells to broaden the utility of the method,
and the use of a transmission electron microscope to achieve sharper images of
ultrastructure.
PMID- 24357378
TI - Correlative fluorescence and electron microscopy of quantum dot labeled proteins
on whole cells in liquid.
AB - Correlative fluorescence microscopy and scanning transmission electron microscopy
(STEM) of cells fully immersed in liquid is a new methodology with many
application areas. Proteins, in live cells immobilized on microchips, are labeled
with fluorescent quantum dot (QD) nanoparticles. In this protocol, the epidermal
growth factor receptor (EGFR) is labeled. The cells are fixed after a selected
labeling time, for example, 5 min as needed to form EGFR dimers. The microchip
with cells is then imaged with fluorescence microscopy. Thereafter, the microchip
with the labeled cells and one with a spacer are assembled in a special
microfluidic device and imaged with STEM.
PMID- 24357379
TI - FIB-SEM tomography in biology.
AB - Three-dimensional information is much easier to understand than a set of two
dimensional images. Therefore a layman is thrilled by the pseudo-3D image taken
in a scanning electron microscope (SEM) while, when seeing a transmission
electron micrograph, his imagination is challenged. First approaches to gain
insight in the third dimension were to make serial microtome sections of a region
of interest (ROI) and then building a model of the object. Serial microtome
sectioning is a tedious and skill-demanding work and therefore seldom done. In
the last two decades with the increase of computer power, sophisticated display
options, and the development of new instruments, an SEM with a built-in microtome
as well as a focused ion beam scanning electron microscope (FIB-SEM), serial
sectioning, and 3D analysis has become far easier and faster.Due to the relief
like topology of the microtome trimmed block face of resin-embedded tissue, the
ROI can be searched in the secondary electron mode, and at the selected spot, the
ROI is prepared with the ion beam for 3D analysis. For FIB-SEM tomography, a thin
slice is removed with the ion beam and the newly exposed face is imaged with the
electron beam, usually by recording the backscattered electrons. The process,
also called "slice and view," is repeated until the desired volume is imaged.As
FIB-SEM allows 3D imaging of biological fine structure at high resolution of only
small volumes, it is crucial to perform slice and view at carefully selected
spots. Finding the region of interest is therefore a prerequisite for meaningful
imaging. Thin layer plastification of biofilms offers direct access to the
original sample surface and allows the selection of an ROI for site-specific FIB
SEM tomography just by its pronounced topographic features.
PMID- 24357380
TI - Correlative light and electron microscopy using immunolabeled sections.
AB - In correlative microscopy, light microscopy provides the overview and orientation
of the complex cells and tissue, while electron microscopy offers the detailed
localization and correlation of subcellular structures. In this chapter we offer
detailed high-quality electron microscopical preparation methods for optimum
preservation of the cellular ultrastructure. From such preparations serial thin
sections are collected and used for comparative histochemical,
immunofluorescence, and immunogold staining.In light microscopy histological
stains identify the orientation of the sample and immunofluorescence labeling
facilitates to find the region of interest, namely, the labeled cells expressing
the macromolecule under investigation. Sections, labeled with immunogold are
analyzed by electron microscopy in order to identify the label within the
cellular architecture at high resolution.
PMID- 24357381
TI - Correlative 3D imaging: CLSM and FIB-SEM tomography using high-pressure frozen,
freeze-substituted biological samples.
AB - Correlative light and electron microscopy aims at combining data from different
imaging modalities, ideally from the same area of the one sample, in order to
achieve a more holistic view of the hierarchical structural organization of cells
and tissues. Modern 3D imaging techniques opened up new possibilities to expand
morphological studies into the third dimension at the nanometer scale. Here we
present an approach to correlate 3D light microscopy data with volume data from
focused ion beam-scanning electron microscopy. An adapted sample preparation
method based on high-pressure freezing for structure preservation, followed by
freeze-substitution for multimodal en bloc imaging, is described. It is based on
including fluorescent labeling during freeze-substitution, which enables
histological context description of the structure of interest by confocal laser
scanning microscopy prior to high-resolution electron microscopy. This
information can be employed to relocate the respective structure in the electron
microscope. This approach is most suitable for targeted small 3D volume
correlation and has the potential to extract statistically relevant data of
structural details for systems biology.
PMID- 24357382
TI - Three-dimensional imaging of adherent cells using FIB/SEM and STEM.
AB - In this chapter we describe three different approaches for three-dimensional
imaging of electron microscopic samples: serial sectioning transmission electron
microscopy (TEM), scanning transmission electron microscopy (STEM) tomography,
and focused ion beam/scanning electron microscopy (FIB/SEM) tomography. With
these methods, relatively large volumes of resin-embedded biological structures
can be analyzed at resolutions of a few nm within a reasonable expenditure of
time. The traditional method is serial sectioning and imaging the same area in
all sections. Another method is TEM tomography that involves tilting a section in
the electron beam and then reconstruction of the volume by back projection of the
images. When the scanning transmission (STEM) mode is used, thicker sections (up
to 1 MUm) can be analyzed. The third approach presented here is focused ion
beam/scanning electron microscopy (FIB/SEM) tomography, in which a sample is
repeatedly milled with a focused ion beam (FIB) and each newly produced block
face is imaged with the scanning electron microscope (SEM). This process can be
repeated ad libitum in arbitrary small increments allowing 3D analysis of
relatively large volumes such as eukaryotic cells. We show that resolution of
this approach is considerably improved when the secondary electron signal is
used. However, the most important prerequisite for three-dimensional imaging is
good specimen preparation. For all three imaging methods, cryo-fixed (high
pressure frozen) and freeze-substituted samples have been used.
PMID- 24357383
TI - X-ray microanalysis in the scanning electron microscope.
AB - X-ray microanalysis conducted using the scanning electron microscope is a
technique that allows the determination of chemical elements in bulk or semi
thick specimens. The lowest concentration of an element that can be detected is
in the order of a few mmol/kg or a few hundred parts per million, and the
smallest amount is in the order of 10(-18) g. The spatial resolution of the
analysis depends on the thickness of the specimen. For biological specimen
analysis, care must be taken to prevent displacement/loss of the element of
interest (usually ions). Protocols are presented for the processing of frozen
hydrated and freeze-dried specimens, as well as for the analysis of small volumes
of fluid, cell cultures, and other specimens. Aspects of qualitative and
quantitative analysis are covered, including limitations of the technique.
PMID- 24357384
TI - Application of SEM and EDX in studying biomineralization in plant tissues.
AB - This chapter describes protocols using formalin-acetic acid-alcohol (FAA) to fix
plant tissues for studying biomineralization by means of scanning electron
microscopy (SEM) and qualitative energy-dispersive X-ray microanalysis (EDX).
Specimen preparation protocols for SEM and EDX mainly include fixation,
dehydration, critical point drying (CPD), mounting, and coating. Gold-coated
specimens are used for SEM imaging, while gold- and carbon-coated specimens are
prepared for qualitative X-ray microanalyses separately to obtain complementary
information on the elemental compositions of biominerals. During the specimen
preparation procedure for SEM, some biominerals may be dislodged or scattered,
making it difficult to determine their accurate locations, and light microscopy
is used to complement SEM studies. Specimen preparation protocols for light
microscopy generally include fixation, dehydration, infiltration and embedding
with resin, microtome sectioning, and staining. In addition, microwave processing
methods are adopted here to speed up the specimen preparation process for both
SEM and light microscopy.
PMID- 24357386
TI - Biological applications of energy-filtered TEM.
AB - The techniques of electron energy-loss spectroscopy (EELS) and energy-filtered
TEM (EFTEM) are routinely applied in the physical sciences to map the
distribution of elements at the nanoscale. EELS can also provide details of the
bonding/valence of elements through variations in the fine structure of elemental
peaks in the spectrum. While applications of these techniques in biology are less
prevalent, their ability to detect both the light elements (e.g., C, N, O, P, S)
that form the building blocks of biological systems and heavier elements (e.g.,
metals) makes them potentially important techniques for investigating local
chemical variations in tissues and cells. Successful application of EELS and
EFTEM in biology requires both an understanding of the techniques themselves and
expertise in specimen preparation. Care must be taken to avoid the diffusion of
elements during the preparation process to avoid artifacts in the resulting
element maps. The power of the techniques is demonstrated here using tissue from
a marine mollusc (chiton).
PMID- 24357385
TI - Freeze stabilization and cryopreparation technique for visualizing the water
distribution in woody tissues by X-ray imaging and cryo-scanning electron
microscopy.
AB - The protocol of freeze stabilization and cryopreparation techniques to examine
the distribution of water in living tree stems by X-ray imaging and cryo-scanning
electron microscopy have been developed and described. The brief procedures are
as follows. Firstly, a portion of transpiring stem is frozen in the standing
state with liquid nitrogen to stabilize the water that is present in the
conducting tissue. After filling with liquid nitrogen, discs are then collected
from the frozen portion of the stem and stored in liquid nitrogen. In a low
temperature room, the samples for X-ray imaging are sectioned with a fine
handsaw, and trimmed sample blokes for cryo-scanning electron microscopy are
cleanly planed using a sliding microtome. Finally, the frozen sections are
irradiated in a soft X-ray apparatus, and the small blocks are examined in cryo
scanning electron microscope after freeze-etching and metal coating.
PMID- 24357387
TI - Secondary ion mass spectrometry imaging of biological cells and tissues.
AB - Secondary ion mass spectrometry (SIMS) is capable of providing detailed atomic
and molecular characterization of the surface chemistry of (bio)molecular
samples. It is one of a range of mass spectrometry imaging techniques that
combine the high sensitivity and specificity of mass spectrometry with the
capability to view the distribution of analytes within solid samples. The
technique is particularly suited to the detection and imaging of small molecules
such as lipids and other metabolites. A limit of detection in the ppm range and
spatial resolution <1 MUm can be obtained. Recent progress in instrumental
developments, including new cluster ion beams, the implementation of tandem mass
spectrometry (MS/MS), and the application of multivariate data analysis protocols
promise further advances. This chapter presents a brief overview of the technique
and methodology of SIMS using exemplar studies of biological cells and tissue.
PMID- 24357388
TI - Elemental and isotopic imaging of biological samples using NanoSIMS.
AB - With its low detection limits and the ability to analyze most of the elements in
the periodic table, secondary ion mass spectrometry (SIMS) represents one of the
most versatile in situ analytical techniques available, and recent developments
have resulted in significant advantages for the use of imaging mass spectrometry
in biological and biomedical research. Increases in spatial resolution and
sensitivity allow detailed interrogation of samples at relevant scales and
chemical concentrations. Advances in dynamic SIMS, specifically with the advent
of NanoSIMS, now allow the tracking of stable isotopes within biological systems
at subcellular length scales, while static SIMS combines subcellular imaging with
molecular identification. In this chapter, we present an introduction to the SIMS
technique, with particular reference to NanoSIMS, and discuss its application in
biological and biomedical research.
PMID- 24357389
TI - 3D chemical mapping: application of scanning transmission (soft) X-ray microscopy
(STXM) in combination with angle-scan tomography in bio-, geo-, and environmental
sciences.
AB - The identification of environmental processes and mechanisms often requires
information on the organochemical and inorganic composition of specimens at high
spatial resolution. X-ray spectroscopy (XAS) performed in the soft X-ray range
(100-2,200 eV) provides chemical speciation information for elements that are of
high biogeochemical relevance such as carbon, nitrogen, and oxygen but also
includes transition metals such as iron, manganese, or nickel. Synchrotron-based
scanning transmission X-ray microscopy (STXM) combines XAS with high resolution
mapping on the 20-nm scale. This provides two-dimensional (2D) quantitative
information about the distribution of chemical species such as organic
macromolecules, metals, or mineral phases within environmental samples.
Furthermore, the combination of STXM with angle-scan tomography allows for three
dimensional (3D) spectromicroscopic analysis of bio-, geo-, or environmental
samples. For the acquisition of STXM tomography data, the sample is rotated
around an axis perpendicular to the X-ray beam. Various sample preparation
approaches such as stripes cut from TEM grids or the preparation of wet cells
allow for preparing environmentally relevant specimens in a dry or in a fully
hydrated state for 2D and 3D STXM measurements. In this chapter we give a short
overview about the principles of STXM, its application to environmental sciences,
different preparation techniques, and the analysis and 3D reconstruction of STXM
tomography data.
PMID- 24357390
TI - 25th anniversary article: MXenes: a new family of two-dimensional materials.
AB - Recently a new, large family of two-dimensional (2D) early transition metal
carbides and carbonitrides, called MXenes, was discovered. MXenes are produced by
selective etching of the A element from the MAX phases, which are metallically
conductive, layered solids connected by strong metallic, ionic, and covalent
bonds, such as Ti2 AlC, Ti3 AlC2 , and Ta4 AlC3 . MXenes -combine the metallic
conductivity of transition metal carbides with the hydrophilic nature of their
hydroxyl or oxygen terminated surfaces. In essence, they behave as "conductive
clays". This article reviews progress-both -experimental and theoretical-on their
synthesis, structure, properties, intercalation, delamination, and potential
applications. MXenes are expected to be good candidates for a host of
applications. They have already shown promising performance in electrochemical
energy storage systems. A detailed outlook for future research on MXenes is also
presented.
PMID- 24357392
TI - Succession.
PMID- 24357394
TI - No evidence for distinguishing bacterial from viral acute rhinosinusitis using
fever and facial/dental pain: a systematic review of the evidence base.
AB - OBJECTIVE: To assess the diagnostic value of fever and facial and dental pain in
adults suspected of acute bacterial rhinosinusitis. DATA SOURCES: PubMed, EMBASE,
and the Cochrane Library. REVIEW METHODS: A comprehensive systematic search was
performed on March 18, 2013. We included articles reporting studies on the
diagnostic value of fever or facial and dental pain in patients suspected of
acute bacterial rhinosinusitis. For included articles, the reported study design
was assessed for directness of evidence and risk of bias. Prevalences, positive
predictive values, and negative predictive values were extracted. RESULTS: Of
3171 unique records, we included 1 study with a high directness of evidence and a
moderate risk of bias. The prior probability of bacterial rhinosinusitis was 0.29
(95% confidence interval: 0.24 to 0.35). We could not extract posterior
probabilities with accompanying positive and negative predictive values. The
study reported an odds ratio from univariate analysis for fever of 1.02 (0.52 to
2.00) and 1.65 (0.83 to 3.28) for facial and dental pain. In subsequent
multivariate analysis, the odds ratio of facial and dental pain was 1.86 (1.06 to
3.29). CONCLUSION AND RECOMMENDATION: There is 1 study with moderate risk of
bias, reporting data in such a manner that we could not assess the value of fever
and facial and dental pain in adults suspected of an acute bacterial
rhinosinusitis. Therefore, these symptoms should not be used in clinical practice
to distinguish between a bacterial and viral source of acute rhinosinusitis or
for decision making about prescribing antibiotic treatment.
PMID- 24357391
TI - DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.
AB - The length of female reproductive lifespan is associated with multiple adverse
outcomes, including breast cancer, cardiovascular disease and infertility. The
biological processes that govern the timing of the beginning and end of
reproductive life are not well understood. Genetic variants are known to
contribute to ~50% of the variation in both age at menarche and menopause, but to
date the known genes explain <15% of the genetic component. We have used genome
wide association in a bivariate meta-analysis of both traits to identify genes
involved in determining reproductive lifespan. We observed significant genetic
correlation between the two traits using genome-wide complex trait analysis.
However, we found no robust statistical evidence for individual variants with an
effect on both traits. A novel association with age at menopause was detected for
a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 * 10(-9)), which
was also associated with altered expression levels of MSH6 mRNA in multiple
tissues. This study contributes to the growing evidence that DNA repair processes
play a key role in ovarian ageing and could be an important therapeutic target
for infertility.
PMID- 24357395
TI - AAO-HNSF CORE grant acquisition is associated with greater scholarly impact.
AB - OBJECTIVE: To determine whether receiving funding from the American Academy of
Otolaryngology--Head and Neck Surgery Foundation (AAO-HNSF) Centralized
Otolaryngology Research Efforts (CORE) grant program is associated with career
choice (in terms of practice setting) and scholarly impact. STUDY DESIGN AND
SETTING: Examination of bibliometrics among academic otolaryngologists, including
CORE grants funding history. METHODS: An Internet search was conducted to
determine the current practice setting and, for academic otolaryngologists,
academic rank of individuals receiving CORE grants since 1985. The Scopus
database was used to determine scholarly impact, as measured by the h-index, and
publication experience (in years) of these practitioners along with a "control"
cohort of nonfunded academic otolaryngologists. RESULTS: Of 432 unique
individuals receiving CORE grant funding since 1985, 44.4% are currently
academicians. This cohort had a higher h-index (mean, 11.9; median, 10;
interquartile range [IQR], 6-18) than their non-CORE grant-funded academic peers
(mean, 9.2; median, 7; IQR, 3-13; P = .002) and colleagues who are not currently
in academic practice (mean, 4.4; median, 3; IQR, 0-6; P < .001). CORE grant
funded academic otolaryngologists had a statistically higher scholarly impact on
controlling for academic rank and among practitioners with greater than 10 years
of publication experience. No statistical differences in academic promotion
patterns were noted between those with and those without a CORE grant funding
history. CONCLUSIONS: Procurement of an AAO-HNSF CORE grant is associated with
greater scholarly impact, as measured by the h-index. This relationship persists
among practitioners with more than 10 years of publication experience, as well as
upon comparison of CORE grant-funded and non-CORE grant-funded otolaryngologists
at all academic ranks. Practitioners awarded these grants may be more likely to
go into and remain in academic practice.
PMID- 24357396
TI - Endoscopic posterior cordotomy with microdissection radiofrequency electrodes for
bilateral vocal cord paralysis.
AB - The purpose of this study is to evaluate the results of endoscopic posterior
cordotomy using microdissection electrodes in patients with bilateral vocal cord
paralysis. Eleven patients underwent endoscopic posterior cordotomy using a
radiofrequency Arrowtip monopolar needle. Preoperative-postoperative exercise
tolerance, airway, and voice evaluation were performed in all patients. Two
patients required a secondary revision operation due to granulation and crust
formation and respiratory problems. No other complications were encountered. Two
patients with tracheotomy cannulas were decannulated on the third postoperative
day. All patients had an adequate functional airway and good exercise tolerance
compared with poor preoperative exercise tolerance. There was no significant
difference between preoperative and postoperative Voice Handicap Index values (P
> .05). The data indicated the safety, easy use, and efficiency of the
microdissection radiofrequency electrodes in patients with bilateral vocal fold
paralysis. This technique provides a reliable alternative to laser procedures.
PMID- 24357397
TI - Metformin reduces TGF-beta1-induced extracellular matrix production in nasal
polyp-derived fibroblasts.
AB - BACKGROUND AND OBJECTS: Metformin is widely used to treat type 2 diabetes
mellitus, and adenosine monophosphate-activated protein kinase (AMPK) is thought
to be the target that mediates its effects. Recently, it has been demonstrated
that metformin has antifibrotic effects beyond its antihyperglycemic action. The
purposes of this study were to investigate the effect of metformin on TGF-beta1
induced myofibroblast differentiation (alpha-smooth muscle actin [alpha-SMA]) and
extracellular matrix (ECM) production and to determine the underlying mechanism
of the action of metformin in nasal polyp-derived fibroblasts (NPDFs). STUDY
DESIGN: Basic research. SETTING: The rhinology laboratory of Korea University
Guro Hospital, Seoul, Korea. METHODS: NPDFs from 7 patients were incubated with
TGF-beta1 and treated with metformin or compound C, an inhibitor of AMPK. To
determine the proliferation rate of nasal fibroblasts, a 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyl tetrazolium bromide assay was performed. The expression levels
of alpha-SMA and fibronectin were determined by reverse transcription-polymerase
chain reaction (RT-PCR), Western blotting, and immunofluorescent staining.
Phosphorylation of AMPK and phosphorylation of Smad2/3 were evaluated by Western
blot analysis. RESULTS: In TGF-beta1-induced NPDFs, metformin inhibited the
expression of alpha-SMA and fibronectin, as confirmed by both RT-PCR and Western
blot analysis. Metformin increased the phosphorylation of AMPK and the expression
levels of alpha-SMA and fibronectin. However, compound C reversed these effects.
Metformin inhibited TGF-beta1-induced phosphorylation of Smad2/3. CONCLUSIONS:
This study showed that metformin inhibits TGF-beta1-induced myofibroblast
differentiation and ECM production in NPDFs via the Smad2/3 pathway. AMPK can be
a therapeutic target for the prevention of ECM remodeling in nasal polyps.
PMID- 24357398
TI - Outcome of fetuses with short femur length detected at second-trimester anomaly
scan: a national survey.
AB - OBJECTIVE: To assess the relationship between the finding of fetal femur
diaphysis length (FL) below the 5(th) percentile at the second-trimester scan and
pregnancy outcome, in a population in which more than 90% of women attend first
trimester screening. METHODS: This was a retrospective study of all Danish
singleton pregnancies with a 17-22-week anomaly scan between 1 January 2008 and
30 June 2011. Information on FL and gestational age (GA) at anomaly scan, on
birth weight and GA at delivery and on chromosomal abnormalities was obtained
from the Danish Fetal Medicine Database. RESULTS: Short FL was identified in 2718
(1.8%) of 147,766 fetuses and was present in 11 (16.2%) of the 68 fetuses
affected by trisomy 21 (positive likelihood ratio (LR+) 8.8 (95% CI, 5.1-15.2)).
Trisomy 13/18 and unbalanced autosomal structural abnormalities were also
associated with a short FL in three (12.0%, LR+ 6.5 (95% CI, 2.3-18.9)) and eight
(32.0%, LR+ 17.4 (95% CI, 9.8-30.9)) of the cases, respectively. The risk of a
fetus having trisomy 21, trisomy 18, trisomy 13 or an unbalanced autosomal
structural abnormality was 1 : 123 (95% CI, 79-192), given a short FL.
Pregnancies with a fetus with short FL were more often affected by early preterm
delivery (before 34 weeks) (5.6%; odds ratio (OR) = 4.2 (95% CI, 3.5-4.9)) and
small-for-gestational-age (SGA) infants (13.9%; OR = 4.3 (95% CI, 3.8-4.8)).
CONCLUSION: Short FL at the second-trimester anomaly scan is associated with a
significantly higher relative risk of chromosomal abnormalities, and a
substantially higher absolute risk for SGA and early preterm delivery.
PMID- 24357399
TI - Beyond Framingham and coronary calcium: predicted lifetime risk identifies
unfavorable risk trajectories.
PMID- 24357401
TI - For some groups traditionally considered to be 'high risk', the evidence of an
increased risk of severe influenza-associated illness is poor quality.
PMID- 24357402
TI - ACC/AHA/SCAI/AMA-Convened PCPI/NCQA 2013 Performance Measures for Adults
Undergoing Percutaneous Coronary Intervention: A Report of the American College
of Cardiology/American Heart Association Task Force on Performance Measures, the
Society for Cardiovascular Angiography and Interventions, the American Medical
Association-Convened Physician Consortium for Performance Improvement, and the
National Committee for Quality Assurance.
PMID- 24357403
TI - Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the
Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study.
AB - BACKGROUND: Percutaneous coronary interventions in patients with chronic kidney
disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the
rate of target vessel revascularization in comparison with bare-metal stents
(BMS) in patients with chronic kidney disease. However, given the multiple
concomitant individual variables present in such patients, the comparison of
neointimal growth after percutaneous coronary intervention is complex and
difficult to assess. METHODS AND RESULTS: Randomized Comparison of Xience V and
Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic
Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to
directly compare the efficacy in the prevention of clinical restenosis of
everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link
Vision), both implanted in the same patient with multivessel coronary artery
disease and chronic kidney disease (estimated glomerular filtration rate <60
mL/min). The primary end point of the study was the ischemia-driven target vessel
revascularization as detected with myocardial scintigraphy at 12 months. In 215
patients, 512 coronary vessels were successfully treated with the randomly
assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven
target vessel revascularization for DES and BMS groups was 2.7% (95% confidence
interval, 1.1%-5.6%) and 11.4% (95% confidence interval, 7.8% to 16%),
respectively, P<0.001. For the multivariate analysis, independent predictors of
the ischemia-driven target vessel revascularization were BMS implantation (odds
ratio, 4.95; 95% confidence interval, 2.1-11.6; P<0.001) and vessel size (odds
ratio, 0.32; 95% confidence interval, 0.1-0.7; P=0.006). CONCLUSIONS: This is the
first randomized trial showing a reduction of clinical restenosis with a new
generation DES in comparison with a BMS of equal design, in patients who have
chronic kidney disease with multivessel coronary artery disease. CLINICAL TRIAL
REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00818792.
PMID- 24357404
TI - Comparison of cardiovascular magnetic resonance and single-photon emission
computed tomography in women with suspected coronary artery disease from the
Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE
MARC) Trial.
AB - BACKGROUND: Coronary artery disease is the leading cause of death in women, and
underdiagnosis contributes to the high mortality. This study compared the sex
specific diagnostic performance of cardiovascular magnetic resonance (CMR) and
single-photon emission computed tomography (SPECT). METHODS AND RESULTS: A total
of 235 women and 393 men with suspected angina underwent CMR, SPECT, and x-ray
angiography as part of the Clinical Evaluation of Magnetic Resonance Imaging in
Coronary Heart Disease (CE-MARC) study. CMR comprised adenosine stress/rest
perfusion, cine imaging, late gadolinium enhancement, and magnetic resonance
coronary angiography. Gated adenosine stress/rest SPECT was performed with
(99m)Tc-tetrofosmin. For CMR, the sensitivity in women and men was similar (88.7%
versus 85.6%; P=0.57), as was the specificity (83.5% versus 82.8%; P=0.86). For
SPECT, the sensitivity was significantly worse in women than in men (50.9% versus
70.8%; P=0.007), but the specificities were similar (84.1% versus 81.3%; P=0.48).
The sensitivity in both the female and male groups was significantly higher with
CMR than SPECT (P<0.0001 for both), but the specificity was similar (P=0.77 and
P=1.00, respectively). For perfusion-only components, CMR outperformed SPECT in
women (area under the curve, 0.90 versus 0.67; P<0.0001) and in men (area under
the curve, 0.89 versus 0.74; P<0.0001). Diagnostic accuracy was similar in both
sexes with perfusion CMR (P=1.00) but was significantly worse in women with SPECT
(P<0.0001). CONCLUSIONS: In both sexes, CMR has greater sensitivity than SPECT.
Unlike SPECT, there are no significant sex differences in the diagnostic
performance of CMR. These findings, plus an absence of ionizing radiation
exposure, mean that CMR should be more widely adopted in women with suspected
coronary artery disease. CLINICAL TRIAL REGISTRATION URL: http://www.controlled
trials.com. Unique identifier: ISRCTN77246133.
PMID- 24357405
TI - Cross-sectional associations of medication and supplement use with retinal
vascular diameter in the Beaver Dam Eye Study.
AB - IMPORTANCE: Retinal vessel diameters are being measured to examine their
relationship with ocular and systemic disease and, in some studies, to calculate
the risk of disease. Important factors that directly affect retinal vessel
diameters, such as medication use, should be considered when estimating these
associations. OBJECTIVE: To quantify the association between selected medications
and supplements and retinal vessel diameters. DESIGN, SETTING, AND PARTICIPANTS:
In a prospective cohort investigation, 4926 participants (aged 43-86 years at
baseline) in the Beaver Dam Eye Study were evaluated every 5 years during 20
years of follow-up from 1988 to 2010. MAIN OUTCOMES AND MEASURES: Central retinal
arteriolar equivalent and central retinal venular equivalent measured from the
Early Treatment Diabetic Retinopathy Study fundus photograph field 1. RESULTS:
After Bonferroni correction, the use of any blood pressure medication (beta =
0.75; P = .04), specifically calcium channel blockers (beta = -1.02; P < .001),
was significantly associated with wider central retinal arteriolar equivalent
adjusting for refraction, photograph focus, age, systolic blood pressure, height,
examination phase, educational level, smoking and drinking histories, and
presence of diabetes mellitus and emphysema. Use of prostaglandin analogues was
marginally associated with narrower central retinal arteriolar equivalent (beta =
-2.04; P = .09); beta-blockers (beta = -1.02; P = .10) and oral corticosteroids
(beta = 2.13; P = .07) were marginally associated with changes in the central
retinal venular equivalent. CONCLUSIONS AND RELEVANCE: Several medications are
associated with central retinal arteriolar and venular equivalents. Prostaglandin
analogues, calcium channel blockers, and oral corticosteroids have the largest
relative effects. After Bonferroni correction was applied, the use of calcium
channel blockers was most strongly associated with change in the central retinal
arteriolar equivalent. The presence of factors that are associated with retinal
vessel diameters should be considered when using retinal vessel diameter as an
outcome or when using these measures to assess the risk of systemic or ocular
disease.
PMID- 24357406
TI - Transfection with follicular dendritic cell secreted protein to affect phenotype
expression of human periodontal ligament cells.
AB - Follicular dendritic cell secreted protein (FDC-SP), has been found to inhibit
osteogenic differentiation of human periodontal ligament cells (hPDLCs) in recent
studies. Based on these findings, we further investigate its effect on phenotype
expression of hPDLCs in the present study, aiming to contribute to a better
understanding of the biological functions governing FDC-SP-induced hPDLC
differentiation. hPDLCs were firstly identified with immunocytochemical staining,
followed by transfection with FDC-SP lentiviral vector. Western blot analysis was
used to confirm the expression of FDC-SP. Then the influence of FDC-SP
transfection on hPDLC proliferation, osteogenic and fibrogenic phenotype
expression was evaluated at the mRNA and protein level. Procollagen type I c
peptide production was measured and alizarin red staining was then conducted to
demonstrate effect of FDC-SP on functional differentiation. We found that hPDLCs
could be successfully transfected with FDC-SP. Cell proliferation and cell cycle
tests indicated that transfection with FDC-SP did not affect hPDLC proliferation.
Moreover, according to real-time PCR and Western blot results, expression levels
of type 1 collagen alpha 1, type 1 collagen alpha 2 and type 3 collagen were
upregulated while that of osteocalcin, osteopontin, and bone sialoprotein were
downregulated in FDC-SP transfected cells. In addition, hPDLCs overexpressing FDC
SP exhibited higher PIP production than the controls. Our findings demonstrate
that transfection with FDC-SP has negligible adverse effect on proliferation of
hPDLCs and imply the biological function of FDC-SP as a fibroblastic phenotype
stabilizer by inhibiting hPDLCs differentiation into mineralized tissue-forming
cells, thus regulating regeneration in periodontal tissue engineering.
PMID- 24357407
TI - Discovery and visualization of miRNA-mRNA functional modules within integrated
data using bicluster analysis.
AB - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene
expression at a post-transcriptional level. An miRNA may target many messenger
RNA (mRNA) transcripts, and each transcript may be targeted by multiple miRNAs.
Our understanding of miRNA regulation is evolving to consider modules of miRNAs
that regulate groups of functionally related mRNAs. Here we expand the model of
miRNA functional modules and use it to guide the integration of miRNA and mRNA
expression and target prediction data. We present evidence of cooperativity
between miRNA classes within this integrated miRNA-mRNA association matrix. We
then apply bicluster analysis to uncover miRNA functional modules within this
integrated data set and develop a novel application to visualize and query these
results. We show that this wholly unsupervised approach can discover a network of
miRNA-mRNA modules that are enriched for both biological processes and miRNA
classes. We apply this method to investigate the interplay of miRNAs and mRNAs in
integrated data sets derived from neuroblastoma and human immune cells. This
study is the first to apply the technique of biclustering to model functional
modules within an integrated miRNA-mRNA association matrix. Results provide
evidence of an extensive modular miRNA functional network and enable
characterization of miRNA function and dysregulation in disease.
PMID- 24357408
TI - Combining DGE and RNA-sequencing data to identify new polyA+ non-coding
transcripts in the human genome.
AB - Recent sequencing technologies that allow massive parallel production of short
reads are the method of choice for transcriptome analysis. Particularly, digital
gene expression (DGE) technologies produce a large dynamic range of expression
data by generating short tag signatures for each cell transcript. These tags can
be mapped back to a reference genome to identify new transcribed regions that can
be further covered by RNA-sequencing (RNA-Seq) reads. Here, we applied an
integrated bioinformatics approach that combines DGE tags, RNA-Seq, tiling array
expression data and species-comparison to explore new transcriptional regions and
their specific biological features, particularly tissue expression or
conservation. We analysed tags from a large DGE data set (designated as
'TranscriRef'). We then annotated 750,000 tags that were uniquely mapped to the
human genome according to Ensembl. We retained transcripts originating from both
DNA strands and categorized tags corresponding to protein-coding genes,
antisense, intronic- or intergenic-transcribed regions and computed their overlap
with annotated non-coding transcripts. Using this bioinformatics approach, we
identified ~34,000 novel transcribed regions located outside the boundaries of
known protein-coding genes. As demonstrated using sequencing data from human
pluripotent stem cells for biological validation, the method could be easily
applied for the selection of tissue-specific candidate transcripts. DigitagCT is
available at http://cractools.gforge.inria.fr/softwares/digitagct.
PMID- 24357409
TI - Dissecting the chromatin interactome of microRNA genes.
AB - Our knowledge of the role of higher-order chromatin structures in transcription
of microRNA genes (MIRs) is evolving rapidly. Here we investigate the effect of
3D architecture of chromatin on the transcriptional regulation of MIRs. We
demonstrate that MIRs have transcriptional features that are similar to protein
coding genes. RNA polymerase II-associated ChIA-PET data reveal that many groups
of MIRs and protein-coding genes are organized into functionally
compartmentalized chromatin communities and undergo coordinated expression when
their genomic loci are spatially colocated. We observe that MIRs display
widespread communication in those transcriptionally active communities. Moreover,
miRNA-target interactions are significantly enriched among communities with
functional homogeneity while depleted from the same community from which they
originated, suggesting MIRs coordinating function-related pathways at
posttranscriptional level. Further investigation demonstrates the existence of
spatial MIR-MIR chromatin interacting networks. We show that groups of spatially
coordinated MIRs are frequently from the same family and involved in the same
disease category. The spatial interaction network possesses both common and cell
specific subnetwork modules that result from the spatial organization of
chromatin within different cell types. Together, our study unveils an entirely
unexplored layer of MIR regulation throughout the human genome that links the
spatial coordination of MIRs to their co-expression and function.
PMID- 24357412
TI - Current status of molecular targeted therapy for hematologic malignancies:
introduction.
PMID- 24357410
TI - Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two
different complexes.
AB - Different pre-ribosomal complexes are formed during ribosome biogenesis, and the
composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA
helicase implicated in ribosome biogenesis, interacts with nucleolar proteins
Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the early
processing steps leading to the production of 18S ribosomal RNA. We also found
that Bfr2 and Enp2 associate with the U3 small nucleolar RNA (snoRNA), the U3
specific protein Mpp10 and various pre-18S ribosomal RNA species. Thus, we
propose that Bfr2, Dbp4 and Enp2 are components of the small subunit (SSU)
processome, a large complex of ~80S. Sucrose gradient sedimentation analyses
indicated that Dbp4, Bfr2 and Enp2 sediment in a peak of ~50S and in a peak of
~80S. Bfr2, Dbp4 and Enp2 associate together in the 50S complex, which does not
include the U3 snoRNA; however, they associate with U3 snoRNA in the 80S complex
(SSU processome). Immunoprecipitation experiments revealed that U14 snoRNA
associates with Dbp4 in the 50S complex, but not with Bfr2 or Enp2. The assembly
factor Tsr1 is not part of the '50S' complex, indicating this complex is not a
pre-40S ribosome. A combination of experiments leads us to propose that Bfr2,
Enp2 and Dbp4 are recruited at late steps during assembly of the SSU processome.
PMID- 24357411
TI - Novel therapeutic strategies using hypomethylating agents in the treatment of
myelodysplastic syndrome.
AB - Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm with high rates
of leukemic transformation. MDS had been an intractable disease for which the
mainstream of therapeutic approach was best supportive care. Recently, however,
treatment of hematological malignancies has benefited from advances in molecular
targeted drug discovery such as the revolutionary drug imatinib for chronic
myeloid leukemia, and from the reappraisal of forgotten drugs such as thalidomide
for multiple myeloma. Two azanucleotide drugs, azacitidine (AZA) and decitabine,
were created as anti-neoplastic drugs in the 1960s with little success. In the
1980s, they were reassessed as hypomethylating agents (HMAs), and the
introduction of low-dose schedules of them has shown dramatic effects in the
delay of leukemic evolution for high-risk MDS. AZA was approved in Japan in March
2011 and has become a standard drug of choice in the treatment of high-risk MDS.
Its position as a treatment for low-risk MDS remains to be established. Only half
of patients with high-risk MDS can gain benefit from AZA. For example, those with
complex karyotypes experience only a limited extension in survival. In addition,
AZA resistance develops sooner or later. To achieve a more sustained disease
control of high-risk MDS, the combined use of HMAs with other therapeutic
approaches will be inevitable. Clinical trials of histone deacetylase inhibitors,
lenalidomide, thrombopoietin agonists, or anticancer drugs in combination with
HMAs are ongoing. In addition, HMAs are being used as a bridging therapy prior to
allogeneic stem cell transplantation (AHSCT) and the salvage therapy of relapsed
disease after AHSCT. Thus, HMAs will continue to be key drugs for the management
of MDS.
PMID- 24357413
TI - Developmental expression and role of Kinesin Eg5 during Xenopus laevis
embryogenesis.
AB - BACKGROUND: The neural crest is a transient multipotent migratory cell population
unique to vertebrates. These cells undergo an epithelial-to-mesenchymal
transition and migrate extensively through the embryo. They differentiate into
numerous diverse derivatives including the peripheral nervous system,
melanocytes,and craniofacial cartilages. The development of the neural crest is
mediated by complex interactions of multiple signals and transcription factors.
The kinesin Eg5 is a plus end-directed microtubule-based motor protein that is
essential for bipolar spindle formation during mitosis and meiosis, axon growth,
and mammal embryonic development. RESULTS: We analyzed in detail the expression
pattern of eg5 and established that it is expressed at the prospective neural
fold, in the premigratory and migratory neural crest. Functional analysis
revealed that in Xenopus, early embryogenesis eg5 function is required during
neural crest induction, specification, and maintenance. eg5 is also required
during neural crest migration and for derivatives formation. Moreover, we
demonstrated a hierarchical relationship with the Indian Hedgehog signaling
pathway. CONCLUSIONS: Our results show that eg5 is essential for the
specification and maintenance of neural crest progenitors during Xenopus early
embryogenesis rather than cell proliferation and survival.
PMID- 24357414
TI - Synthesis, characterization and biodistribution studies of (125)I-radioiodinated
di-PEGylated bone targeting salmon calcitonin analogue in healthy rats.
AB - PURPOSE: The objective of this study was to prepare a bisphosphonate (BP)
mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as
a novel bone targeting pharmaceutical. METHODS: HPLC was used for isolation of
sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible
PEGylation sites by trypsin digestion. Stability of the compound over time, bone
mineral affinity using hydroxyapatite, and biodistribution in normal rats after
radiolabeling of sCT-2(PEG-BP) or control sCT with (125)I was evaluated. RESULTS:
PEGylated sCT analogues were synthesized, and sCT-2(PEG-BP) was isolated by HPLC
and confirmed by MALDI-TOF and ICP-MS. MALDI-TOF analysis of trypsinized
fragments suggested Cys(1) (or Lys(11)) and Lys(18) to be the two PEGylation
sites. Bone mineral affinity test showed sCT-2(PEG-BP) or (125)I-sCT-2(PEG-BP)
exhibited significantly increased bone mineral affinity over sCT or (125)I-sCT,
respectively. sCT-2(PEG-BP) remained stable for at least 1 month. In vivo
biodistribution study showed significantly increased bone retention and prolonged
plasma circulation time for sCT-2(PEG-BP) compared to the control sCT.
CONCLUSION: Those results support sCT-2(PEG-BP) as a promising new drug candidate
for the treatment of resorptive and/or maladaptive bone conditions, such as
Osteoporosis, Osteoarthritis, Rheumatoid Arthritis, Paget's disease and bone
cancers.
PMID- 24357415
TI - IL-21 is increased in peripheral blood of emphysema mice and promotes Th1/Tc1
cell generation in vitro.
AB - Interleukin-21 (IL-21) has been reported to be involved in many Th1-associated
diseases. However, the alteration and immune regulation of IL-21 in emphysema
remains unknown. In this study, we tested the levels of IFN-gamma and IL-21 and
the frequencies of Th1 and Tc1 in peripheral blood from cigarette smoke (CS)
exposed mice and air-exposed mice and explored the effect of IL-21 on generation
of Th1 and Tc1 cells in vitro. It was found that the levels of IFN-gamma and IL
21 and the frequencies of Th1, Tc1, CD4(+) IL-21(+), CD4(+) IL-21R(+), and CD8(+)
IL-21R(+) T cells were much higher in CS-exposed mice. Moreover, the levels of IL
21 were correlated positively with Th1 cells and with Tc1 cells. Finally, the in
vitro experiments showed that IL-21 could promote Th1/Tc1 cell generation in CS
exposed mice. These results indirectly provide evidence that IL-21 produced by
CD4(+) T cells could promote Th1/Tc1 response, leading to systemic inflammation
in emphysema.
PMID- 24357416
TI - Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound
healing and inhibits pro-inflammatory cytokines.
AB - The purpose of this study was to evaluate transcutaneous electrical nerve
stimulation (TENS) and other common treatment methods used in the process of
wound healing in terms of the expression levels of pro-inflammatory cytokines. In
the study, 24 female and 24 male adult Wistar-Albino rats were divided into five
groups: (1) the non-wounded group having no incision wounds, (2) the control
group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the
physiological saline (PS) group and (5) the povidone iodine (PI) group. In the
skin sections, interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and tumor
necrosis factor-alpha (TNF-alpha) were assessed with enzyme-linked immunosorbent
assay and immunohistochemical methods. In the non-wounded group, the expression
of IL-1beta, IL-6, and TNF-alpha signaling molecules was weaker in the whole
tissue; however, in the control group, significant inflammatory response
occurred, and strong cytokine expression was observed in the dermis, granulation
tissue, hair follicles, and sebaceous glands (P < 0.05). In the TENS group, the
decrease in TNF-alpha, IL-1beta, and IL-6 immunoreaction in the skin was
significant compared to the other forms of treatment (P < 0.05). Distinctive
decreases of pro-inflammatory cytokines observed in the dermis in the TENS group
suggest that TENS shortened the healing process by inhibating the inflammation
phase.
PMID- 24357417
TI - Nicotine mediates hypochlorous acid-induced nuclear protein damage in mammalian
cells.
AB - Activated neutrophils secrete hypochlorous acid (HOCl) into the extracellular
space of inflamed tissues. Because of short diffusion distance in biological
fluids, HOCl-damaging effect is restricted to the extracellular compartment. The
current study aimed at investigating the ability of nicotine, a component of
tobacco and electronic cigarettes, to mediate HOCl-induced intracellular damage.
We report, for the first time, that HOCl reacts with nicotine to produce nicotine
chloramine (Nic-Cl). Nic-Cl caused dose-dependent damage to proliferating cell
nuclear antigen (PCNA), a nuclear protein, in cultured mammalian lung and kidney
cells. Vitamin C, vitamin E analogue (Trolox), glutathione, and N-acetyl-L
cysteine inhibited the Nic-Cl-induced PCNA damage, implicating oxidation in PCNA
damage. These findings point out the ability of nicotine to mediate HOCl-induced
intracellular damage and suggest antioxidants as protective measures. The results
also raise the possibility that Nic-Cl can be created in the inflamed tissues of
tobacco and electronic cigarette smokers and may contribute to smoking-related
diseases.
PMID- 24357419
TI - Expanding the clinical phenotype of patients with a ZDHHC9 mutation.
AB - In 2007, 250 families with X-linked intellectual disability (XLID) were screened
for mutations in genes on the X-chromosome, and in 4 of these families, mutations
in the ZDHHC9 gene were identified. The ID was either isolated or associated with
a marfanoid habitus. ZDHHC9 encodes a palmitoyl transferase that catalyzes the
posttranslational modification of NRAS and HRAS. Since this first description, no
additional patient with a ZDHHC9 mutation has been reported in the literature.
Here, we describe a large family in which we identified a novel pathogenic ZDHHC9
nonsense mutation (p.Arg298*) by parallel sequencing of all X-chromosome exons.
The mutation cosegregated with the clinical phenotype in this family. An 18-year
old patient and his 40-year-old maternal uncle were evaluated. Clinical
examination showed normal growth parameters, lingual fasciculation, limited
extension of the elbows and metacarpophalangeal joints, and acrocyanosis. There
was neither facial dysmorphism nor marfanoid habitus. Brain MRI detected a
dysplastic corpus callosum. Neuropsychological testing showed mild intellectual
disability. They both displayed generalized anxiety disorder, and the younger
patient also suffered from significant behavior impairment that required
attention or treatment. Speech evaluation detected satisfactory spoken language
since both were able to provide information and to understand conversations of
everyday life. Occupational therapy examination showed impaired visual-spatial
and visual-motor performance with poor drawing/graphic skills. These
manifestations are not specific enough to guide ZDHHC9 screening in patients with
ID, and emphasize the value of next generation sequencing for making a molecular
diagnosis and genetic counseling in families with XLID.
PMID- 24357418
TI - Surgery for post-vitrectomy cataract.
AB - BACKGROUND: Cataract formation or acceleration can occur after intraocular
surgery, especially following vitrectomy, a surgical technique for removing the
vitreous which is used in the treatment of disorders that affect the posterior
segment of the eye. The underlying problem that led to vitrectomy may limit the
benefit from cataract surgery. OBJECTIVES: The objective of this review was to
evaluate the effectiveness and safety of surgery for post-vitrectomy cataract
with respect to visual acuity, quality of life, and other outcomes. SEARCH
METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group
Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE
in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid
OLDMEDLINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013, Latin
American and Caribbean Health Sciences Literature Database (LILACS) (January 1982
to May 2013), PubMed (January 1946 to May 2013), the metaRegister of Controlled
Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov
(www.clinicaltrial.gov) and the WHO International Clinical Trials Registry
Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or
language restrictions in the electronic searches for trials. We last searched the
electronic databases on 22 May 2013. SELECTION CRITERIA: We planned to include
randomized and quasi-randomized controlled trials comparing cataract surgery with
no surgery in adult patients who developed cataract following vitrectomy. DATA
COLLECTION AND ANALYSIS: Two authors screened the search results independently
according to the standard methodological procedures expected by The Cochrane
Collaboration. MAIN RESULTS: We found no randomized or quasi-randomized
controlled trials comparing cataract surgery with no cataract surgery for
patients who developed cataracts following vitrectomy surgery. AUTHORS'
CONCLUSIONS: There is no evidence from randomized or quasi-randomized controlled
trials on which to base clinical recommendations for surgery for post-vitrectomy
cataract. There is a clear need for randomized controlled trials to address this
evidence gap. Such trials should stratify participants by their age, the retinal
disorder leading to vitrectomy, and the status of the underlying disease process
in the contralateral eye. Outcomes assessed in such trials may include gain of
vision on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, quality
of life, and adverse events such as posterior capsular rupture. Both short-term
(six-month) and long-term (one-year or two-year) outcomes should be examined.
PMID- 24357420
TI - Comparison of intravenous and intraperitoneal lignocaine for pain relief
following laparoscopic cholecystectomy: a double-blind, randomized, clinical
trial.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is increasingly being performed as
a day-care surgery. Intraperitoneal (IP) instillation of lignocaine has been
proved to provide pain relief following LC. Of late, there is an increased
interest in using intravenous (IV) lignocaine to provide pain relief following
LC. There are no studies in the existing literature as to which form of
administration is more effective for pain relief. Hence, this study has been
undertaken. METHODS: Patients (n = 50) undergoing LC for symptomatic
cholelithiasis were randomized into two groups (n = 25 each) to receive IV 2 %
lignocaine from induction until 1 h after surgery or IP instillation of 0.2 %
lignocaine in the gallbladder fossa after removal of gallbladder. Postoperative
analgesic requirement, pain scores, time to return of bowel activity, and stress
response were assessed. RESULTS: The mean total morphine requirement (p = 0.001),
median VAS, first analgesic requirement time (p < 0.001), and total PCA demands
(p < 0.001) during the 24-h period were statistically significantly less in the
IV group compared with the IP group. Return of bowel activity was earlier in the
IV group, and it was statistically significant (p < 0.001). However, stress
response, respiratory function, and postoperative nausea and vomiting were not
significant statistically among the two groups. CONCLUSIONS: IV lignocaine is
superior to IP lignocaine in providing pain relief following LC. IV lignocaine
has an added advantage of bringing about the early return of bowel activity,
which will further facilitate surgeons to perform LC as a day-care procedure.
PMID- 24357421
TI - Performance analysis on physical simulator of four different instrument setups in
laparo-endoscopic single-site (LESS) surgery.
AB - BACKGROUND: Over the past decades, minimally invasive surgery has undergone
continuous development due to the demand for scarless results, with laparo
endoscopic single-site (LESS) surgery constituting one of today's most favored
alternatives. In this study, we aim to assess the relative technical difficulty
and performance benefits of dynamic articulating and pre-bent instruments, either
combined with conventional laparoscopic tools or not, during the completion of
two basic tasks hands-on simulator. METHODS: A total of 20 surgeons were included
and performed two basic simulator tasks-coordination and cutting-carried out
using four different combinations of LESS-designed and straight conventional
laparoscopy instruments. Assessment took place before and after the completion of
a 14-week training program. Performance data were objectively analyzed over video
recordings with an adapted global rating scale (a-GRS) for performance
evaluation, combined with a registry of total trial completion time. RESULTS: In
the coordination task, the worst performance scores (p < 0.001) and longest
completion times (p < 0.001 on first assessment and p < 0.01 on last assessment)
were obtained with the two dynamic articulating tip instruments. On the cut
trials, no significant differences between the different setups were found in a
GRS scores. The two dynamic articulating tip instruments also constituted the
most time-demanding setup on both assessment trials (p < 0.05). The use of two
dynamic articulating tip instruments showed significant improvement with training
in all measured parameters except for performance in the cut task, in which the
increase in a-GRS score was not significant. CONCLUSIONS: We conclude that the
least adequate instrument set for initiation in LESS surgery is the one that
combines two dynamic articulating tip instruments, as this has consistently
obtained the worst results in all trials. Further data on more complex tasks and
on a complete learning and skills-acquisition program must be obtained to confirm
these findings.
PMID- 24357422
TI - Review of robotic versus conventional laparoscopic surgery.
PMID- 24357423
TI - Prophylactic intraperitoneal mesh placement to prevent incisional hernia after
stoma reversal: a feasibility study.
AB - BACKGROUND: Incisional hernias in old stoma wounds occur in one-third of former
stoma patients and pose a significant clinical problem. Parastomal hernias can be
prevented by prophylactic mesh placement; however, no trial results are available
for incisional hernia prevention after stoma reversal. In this feasibility study,
we explore the safety of placing an intraperitoneal mesh to prevent incisional
herniation after temporary stoma reversal. METHODS: Ten patients who underwent a
low anterior resection with a deviating double-loop stoma for rectal cancer
received an intraperitoneal parastomal mesh at the time of stoma formation. At
stoma reversal, laparoscopy was performed and adhesions were scored. After
reversal, the mesh defect was closed. Mesh and stoma complications were closely
monitored. Incisional herniation was assessed at the 2-year follow-up after stoma
reversal using ultrasonography. RESULTS: No infections occurred after mesh
placement. After a median of 6 months, stomas were reversed. Laparoscopy could be
performed in seven patients; all patients had adhesions (median of 25 % of mesh
surface). In three patients, the bowel was involved; one required a laparotomy
for bowel mobilization during stoma reversal. No adhesion-related morbidity was
noted at any time. Except for one superficial wound infection after stoma
reversal, no infectious complications were observed. After a median follow-up of
26 months, no incisional herniations were demonstrated. CONCLUSIONS: Prophylactic
mesh placement in temporary stoma formations seems safe and feasible and prevents
incisional herniation 2 years after stoma reversal.
PMID- 24357425
TI - What should be the correct indications for laparoscopic inguinal hernia repair?
PMID- 24357424
TI - International consensus on safe techniques and error definitions in laparoscopic
surgery.
AB - BACKGROUND: Definitions of errors and poor technique in laparoscopic surgery are
lacking in modern clinical practice. As a result, educators often base their
teaching on personal experience and individual preferences. The objective of this
study was to achieve expert consensus regarding these definitions in order to
provide a framework for a standardized approach to teaching safe technique and
avoiding common errors in laparoscopic surgery. METHODS: A Delphi survey was
conducted with an international panel of experts in laparoscopic surgery. Survey
items for definitions and examples of errors and resulting injuries (events) were
derived from literature reviews and procedural observations. An online platform
was used to administer the survey. Experts were requested to rate their level of
agreement regarding survey items on a 5-point Likert-type scale; additional
comments were facilitated through free-text entries. Consensus was defined as
Cronbach's alpha > 0.70. Items that were rated >= 3 ("somewhat agree") by 75 % or
more of the panel were included in the consensus list. The Delphi process was
continued until all subsections of the survey met the defined consensus level.
RESULTS: Two survey rounds were completed with 33 experts from 12 countries
(round 1) and 25 experts from nine countries (round 2). Overall consensus was
high for both rounds (alpha = 0.9). Seventeen definitions and 39 examples of
errors and events were included in the final consensus list. CONCLUSIONS:
Standardized definitions and examples of technical errors in laparoscopic surgery
were established using a consensus-based approach. These definitions can serve as
uniform nomenclature and can be used by educators as a reference guide to ensure
standardization in surgical training and performance assessment.
PMID- 24357426
TI - Understanding the relationship between biotherapeutic protein stability and solid
liquid interfacial shear in constant region mutants of IgG1 and IgG4.
AB - Relative stability of therapeutic antibody candidates is currently evaluated
primarily through their response to thermal degradation, yet this technique is
not always predictive of stability in manufacture, shipping, and storage. A
rotating disk shear device is proposed that produces defined shear conditions at
a known solid-liquid interface to measure stability in this environment. Five
variants of IgG1 and IgG4 antibodies were created using combinations of two
discrete triple amino acid sequence mutations denoted TM and YTE. Antibodies were
ranked for stability based on shear device output (protein decay coefficient,
PDC), and compared with accelerated thermal stability data and the melting
temperature of the CH2 domain (Tm 1) from differential scanning calorimetry to
investigate technique complimentarity. Results suggest that the techniques are
orthogonal, with thermal methods based on intramolecular interaction and shear
device stability based on localized unfolding revealing less stable regions that
drive aggregation. Molecular modeling shows the modifications' effects on the
antibody structures and indicates a possible role for Fc conformation and Fab-Fc
docking in determining suspended protein stability. The data introduce the PDC
value as an orthogonal stability indicator, complementary to traditional thermal
methods, allowing lead antibody selection based on a more full understanding of
process stability.
PMID- 24357427
TI - Severe clinical presentation in monozygotic twins with 10p15.3 microdeletion
syndrome.
AB - Submicroscopic deletion of 10p15.3 is a rare genetic disorder, currently reported
in 21 unrelated patients. It is mainly associated with cognitive deficits, speech
disorders, motor delay and hypotonia. The size of the deleted region ranges
between 0.15 and 4 Mb and does not generally correlate with phenotype. A
monozygotic female twin pair with a de novo 2.7 Mb deletion of 10p15.3 is herein
reported. The girls presented at the age of 8 months with severe developmental
delay and failure to thrive since the first month of life. Their perinatal and
family history was unremarkable. On admission they both exhibited generalized
dystonia, microcephaly, complete absence of voluntary movements and
visual/auditory unresponsiveness. Their brain MRIs demonstrated dilatation of
ventricles, subarachnoid spaces and anterior interhemispheric fissure and sylvian
fissures bilaterally. Cranial radiography revealed partial fusion of both coronal
sutures. Visual and brainstem auditory evoked potentials were markedly abnormal,
indicating severe visual and sensorineural hearing impairment. The
electroencephalogram, as well as a screening for inborn errors of metabolism,
were unremarkable. Both patients required gastrostomy and tracheostomy before the
age of 1 year. They were, additionally, managed with physical therapy, as well as
baclofen and low-dose haloperidol. Their current state at the age of 2 years is
relatively stable. The index patients' phenotype includes features, such as
dystonic cerebral palsy, visual and sensorineural hearing impairment or
craniosynostosis, which have not been previously reported in individuals with
10p15.3 deletion. It is necessary to consider these novel clinical features and
investigate their possible relationship with the recently recognized syndrome.
PMID- 24357428
TI - Bruton's tyrosine kinase (BTK) inhibitors in clinical trials.
AB - BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a
variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue
homing receptors. Genetic BTK deletion causes B-cell immunodeficiency in humans
and mice, making this kinase an attractive therapeutic target for B-cell
disorders. The BTK inhibitor ibrutinib (PCI-32765, brand name: Imbruvica)
demonstrated high clinical activity in B-cell malignancies, especially in
patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and
Waldenstrom's macroglobulinemia (WM). Therefore, ibrutinib was granted a
'breakthrough therapy' designation for these indications and was recently
approved for the treatment of relapsed MCL by the U.S. Food and Drug
Administration. Other BTK inhibitors in earlier clinical development include CC
292 (AVL-292), and ONO-4059. In CLL and MCL, ibrutinib characteristically induces
redistribution of malignant B cells from tissue sites into the peripheral blood,
along with rapid resolution of enlarged lymph nodes and a surge in lymphocytosis.
With continuous ibrutinib therapy, growth- and survival-inhibitory activities of
ibrutinib result in the normalization of lymphocyte counts and remissions in a
majority of patients. This review discusses the clinical advances with BTK
inhibitor therapy, as well as its pathophysiological basis, and outlines
perspectives for future use of BTK inhibitors.
PMID- 24357429
TI - Cell wall structure suitable for surface display of proteins in Saccharomyces
cerevisiae.
AB - A display system for adding new protein functions to the cell surfaces of
microorganisms has been developed, and applications of the system to various
fields have been proposed. With the aim of constructing a cell surface
environment suitable for protein display in Saccharomyces cerevisiae, the cell
surface structures of cell wall mutants were investigated. Four cell wall mutant
strains were selected by analyses using a GFP display system via a GPI anchor.
beta-Glucosidase and endoglucanase II were displayed on the cell surface in the
four mutants, and their activities were evaluated. mnn2 deletion strain exhibited
the highest activity for both the enzymes. In particular, endoglucanase II
activity using carboxymethylcellulose as a substrate in the mutant strain was 1.9
fold higher than that of the wild-type strain. In addition, the activity of
endoglucanase II released from the mnn2 deletion strain by Zymolyase 20T
treatment was higher than that from the wild-type strain. The results of green
fluorescent protein (GFP) and endoglucanase displays suggest that the amounts of
enzyme displayed on the cell surface were increased by the mnn2 deletion. The
enzyme activity of the mnn2 deletion strain was compared with that of the wild
type strain. The relative value (mnn2 deletion mutant/wild-type strain) of
endoglucanase II activity using carboxymethylcellulose as a substrate was higher
than that of beta-glucosidase activity using p-nitrophenyl-beta-glucopyranoside
as a substrate, suggesting that the cell surface environment of the mnn2 deletion
strain facilitates the binding of high-molecular-weight substrates to the active
sites of the displayed enzymes.
PMID- 24357430
TI - Technical review: colocalization of antibodies using confocal microscopy.
PMID- 24357431
TI - Highly efficient non-precious metal electrocatalysts prepared from one-pot
synthesized zeolitic imidazolate frameworks.
AB - A facile synthesis of non-PGM ORR electrocatalysts through thermolysis of one-pot
synthesized ZIF is demonstrated. The electrocatalysts exhibit excellent activity,
with a maximum volumetric current density of 88.1 A cm(-3) measured at 0.8 V in
PEFC tests. This approach not only makes ZIFs-based electrocatalysts easy to
scale up, but also paves the way for the tailored synthesis of electrocatalysts.
PMID- 24357432
TI - Cost-effectiveness of prenatal screening strategies for congenital heart disease.
AB - OBJECTIVE: The economic implications of strategies to improve prenatal screening
for congenital heart disease (CHD) in low-risk mothers have not been explored.
The aim was to perform a cost-effectiveness analysis of different screening
methods. METHODS: We constructed a decision analytic model of CHD prenatal
screening strategies (four-chamber screen (4C), 4C + outflow, nuchal translucency
(NT) or fetal echocardiography) populated with probabilities from the literature.
The model included whether initial screens were interpreted by a maternal-fetal
medicine (MFM) specialist and different referral strategies if they were read by
a non-MFM specialist. The primary outcome was the incremental cost per defect
detected. Costs were obtained from Medicare National Fee estimates. A
probabilistic sensitivity analysis was undertaken on model variables commensurate
with their degree of uncertainty. RESULTS: In base-case analysis, 4C + outflow
referred to an MFM specialist was the least costly strategy per defect detected.
The 4C screen and the NT screen were dominated by other strategies (i.e. were
more costly and less effective). Fetal echocardiography was the most effective,
but most costly. On simulation of 10 000 low-risk pregnancies, 4C + outflow
screen referred to an MFM specialist remained the least costly per defect
detected. For an additional $580 per defect detected, referral to cardiology
after a 4C + outflow was the most cost-effective for the majority of iterations,
increasing CHD detection by 13 percentage points. CONCLUSIONS: The addition of
examination of the outflow tracts to second-trimester ultrasound increases
detection of CHD in the most cost-effective manner. Strategies to improve outflow
tract imaging and to refer with the most efficiency may be the best way to
improve detection at a population level.
PMID- 24357433
TI - Anger is associated with increased IL-6 stress reactivity in women, but only
among those low in social support.
AB - BACKGROUND: Social connections moderate the effects of high negative affect on
health. Affective states (anger, fear, and anxiety) predict interleukin-6 (IL-6)
reactivity to acute stress; in turn, this reactivity predicts risk of
cardiovascular disease progression. PURPOSE: Here, we examined whether perceived
social support mitigates the relationship between negative affect and IL-6 stress
reactivity. METHOD: Forty-eight postmenopausal women completed a standardized
mental lab stressor with four blood draws at baseline and 30, 50, and 90 min
after the onset of the stressor and anger, anxiety, and fear were assessed 10 min
after task completion. Participants self-rated levels of social support within a
week prior to the stressor. RESULTS: Only anger was related to IL-6 stress
reactivity-those experiencing high anger after the stressor had significant
increases in IL-6. IL-6 reactivity was marginally associated with perceived
support, but more strikingly, perceived support mitigated anger associations with
IL-6 stress reactivity. CONCLUSION: Supportive ties can dampen the relationship
of anger to pro-inflammatory reactivity to acute stress. Implications to
cardiovascular disease are discussed.
PMID- 24357434
TI - Clinical predictors of long-term outcomes in patients with critical limb ischemia
who have undergone endovascular therapy.
AB - Clinical predictors of long-term outcomes in patients with critical limb ischemia
(CLI) treated with endovascular therapy (EVT) remain unclear. In this study,
clinical predictors of long-term outcomes in EVT-treated patients with CLI were
investigated. In this prospective, observational study, we analyzed a total of
253 Taiwanese patients with CLI with 314 limbs who underwent EVT between 2005 and
2012. Cox models were used to estimate hazard ratios of death, limb loss, and
sustained clinical success (SCS). Multivariate analysis showed that age, atrial
fibrillation (AF), end-stage renal disease (ESRD), and albumin were significant
predictors of mortality. Patients with coronary artery disease and low albumin
levels had a significant risk of major limb amputation, while AF, ESRD, and
albumin were significant, independent predictors of SCS. In addition to
previously reported predictors, we showed that AF and malnutrition can be used to
predict long-term outcome in EVT-treated patients with CLI.
PMID- 24357436
TI - Mouse Models of Huntington's Disease.
AB - In this review, we explore the similarities and differences in the behavioural
neurobiology found in the mouse models of Huntington's disease (HD) and the human
disease state. The review is organised with a comparative focus on the functional
domains of motor control, cognition and behavioural disturbance (akin to
psychiatric disturbance in people) and how our knowledge of the underlying
physiological changes that are manifest in the HD mouse lines correspond to those
seen in the HD clinical population. The review is framed in terms of functional
circuitry and neurotransmitter systems and how abnormalities in these systems
impact on the behavioural readouts across the mouse lines and how these may
correspond to the deficits observed in people. In addition, interpretational
issues associated with the data from animal studies are discussed.
PMID- 24357435
TI - Updated assays for inhibin B and AMH provide evidence for regular episodic
secretion of inhibin B but not AMH in the follicular phase of the normal
menstrual cycle.
AB - STUDY QUESTION: What is the daily variation in serum inhibin B (InhB) and anti
Mullerian hormone (AMH) in relation to the LH surge in women of reproductive age.
SUMMARY ANSWER: AMH is secreted in a biphasic follicular/luteal pattern in women
with higher AMH secretion, while InhB secretion is episodic in the early to mid
follicular phase and immediately after the LH surge but not in the luteal phase.
WHAT IS KNOWN ALREADY: In women of reproductive age with a mean serum AMH >1
ng/ml, levels are highest in Days 2-7 of the cycle. InhB concentrations are
highest in the follicular phase of the cycle. STUDY DESIGN, SIZE, DURATION: In
this cohort study conducted in an academic center, blood samples were collected
daily from 20 women during one normal menstrual cycle. PARTICIPANTS/MATERIALS,
SETTING, METHODS: Regularly menstruating 30- to 40-year-old women had daily serum
InhB, AMH, LH and FSH levels measured. Intracycle variability of InhB and AMH
were assessed after aligning to the LH surge. MAIN RESULTS AND THE ROLE OF
CHANCE: When classified into quartiles of AMH concentration, the lowest AMH
levels did not vary across the cycle; the highest AMH levels showed a mid
follicular increase, mid-cycle decrease and mid-luteal increase. A surge of InhB
was noted following the LH surge in 16/20 cycles. Episodic increases in InhB
occurred in 17/20 cycles prior to the LH surge. In the luteal phase, InhB
decreased or became undetectable and did not demonstrate episodic secretion. Old
and new assays for AMH and InhB were compared in all samples, with the AMH assays
demonstrating good correlation (Rsq = 0.9625) but the InhB assays showing less
correlation (Rsq = 0.4903). LIMITATIONS, REASONS FOR CAUTION: The study
population is small and in the mid-to-late reproductive age group. Single daily
sampling may not detect more frequent variability (i.e. pulses) in hormone
levels. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest different
regulatory mechanisms for InhB and AMH secretion, and confirm an 'aging ovary'
pattern of AMH and InhB secretion, which is consistent with decreased ovarian
reserve. We also demonstrated comparability of the AMH Gen II assay with the
previous version in standard usage but our data raised concerns about
comparability of the InhB Gen II assay. STUDY FUNDING/COMPETING INTEREST(S):
General Clinical Research Center for phlebotomy work has been supported in part
by NIH grant UL1RR024986. Recruitment and data analyses were supported by the
Center for Integrated Approaches to Complex Diseases (SD Harlow, Director). The
authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
PMID- 24357437
TI - The neurobiology of childhood structural brain development: conception through
adulthood.
AB - The study of the function and structure of the human brain dates back centuries,
when philosophers and physicians theorized about the localization of specific
cognitive functions and the structure and organization of underlying brain
tissue. In more recent years, the advent of non-invasive techniques such as
Magnetic Resonance Imaging (MRI) has allowed scientists unprecedented
opportunities to further our understanding not only of structure and function,
but of trajectories of brain development in typical and a-typical child and adult
populations. In this chapter, we hope to provide a system-level approach to
introduce what we have learned about structural brain development from conception
through adulthood. We discuss important findings from MRI studies, and the
directions that future imaging studies can take in the concerted effort to
enhance our understanding of brain development, and thus to enhance our ability
to develop interventions for various neurodevelopmental disorders.
PMID- 24357438
TI - Antisocial and callous behaviour in children.
AB - Antisocial behaviour is one of the most common reasons for a childhood referral
to mental health and educational services and represents a substantial public
health cost. Callous-unemotional traits can be used to distinguish children who
are capable of pre-meditated antisocial behaviour and violence from those whose
antisocial behaviour and violence are primarily impulsive and threat reactive.
Decades of developmental psychopathology research have shown that children with
antisocial behaviour are thus a heterogeneous group and, for interventions to be
successful, it is critical that distinct subgroups of children receive services
that best match their profile of vulnerabilities and strengths. Recent advances
in genetic and brain imaging research in the field have made important
contributions to our understanding of the developmental vulnerability that
callous-unemotional traits represent. In this chapter, we provide an overview of
the current evidence base with regard to genetic and neuroscience findings of
callous-unemotional traits and antisocial behaviour with callous-unemotional
traits. We also discuss the implications of these findings for prevention and
intervention, and finish by outlining what we consider are necessary directions
for future research.
PMID- 24357439
TI - Focal nodular hyperplasia-like lesion in a cirrhotic liver mimicking a
cholangiocarcinoma.
PMID- 24357440
TI - Improved tissue sections for medical liver biopsies: a comparison of 16 vs 18 g
biopsy needles using digital pathology.
AB - BACKGROUND: Most medical liver biopsies in the UK are now taken in radiology
departments using 18 g biopsy needles. Subjectively, the resulting biopsies are
narrow and fragile. AIM: To compare the quality of liver biopsy tissue sections
obtained from 16 and 18 g biopsy needles. METHOD: Fifty consecutive routine
medical liver biopsies obtained with 16 and 18 g needles, processed identically
in the same laboratory, were measured using digital pathology software. We
recorded their fragmentation, length, width, area and number of portal tracts.
RESULTS: Biopsies obtained with 16 g needles more often resulted in an intact
core in tissue sections than those with 18 g needles (71% vs 24%, p<0.001) and
were significantly wider (average width of tissue 0.88 vs 0.53 mm, p<0.001). The
average total area of tissue per pass was 11.38 mm(2) compared with 8.34 mm(2)
(p<0.001). The number of complete portal tracts per length of biopsy was very
variable, but double for 16 vs 18 g biopsies. Routinely taking two passes with
the 18 g needle compensated for the reduced area, but the resulting liver in
tissue sections was fragmented and distorted. CONCLUSIONS: Our results support
the routine use of 16 g rather than 18 g biopsy needles for routine ultrasound
guided medical liver biopsies. A second pass should be considered if the first
biopsy core is short, especially for investigation of disease stage.
PMID- 24357441
TI - An intravascular large B-cell lymphoma with a t(3;14)(q27;q32) translocation.
AB - A 61-year-old man with no symptom was found with bilateral adrenal nodules on CT
scan during a routine physical check-up. The left nodule was removed by
adrenalectomy, and the patient was diagnosed with intravascular large B-cell
lymphoma (IVLBCL) on pathological and immunohistochemical examinations. Using a
set of dual-colour, break-apart probes and fluorescence in situ hybridisation, it
was revealed that the lymphoma cells have tetraploid karyotype, with a breakpoint
in BCL6 gene, which was further confirmed as a t(3;14)(q27;q32) translocation. To
the best of our knowledge, this is the first report of IVLBCL with such a
translocation.
PMID- 24357442
TI - Uric acid and xanthine oxidoreductase in wound healing.
AB - Chronic wounds are an important health problem because they are difficult to heal
and treatment is often complicated, lengthy and expensive. For a majority of
sufferers the most common outcomes are long-term immobility, infection and
prolonged hospitalisation. There is therefore an urgent need for effective
therapeutics that will enhance ulcer healing and patient quality of life, and
will reduce healthcare costs. Studies in our laboratory have revealed elevated
levels of purine catabolites in wound fluid from patients with venous leg ulcers.
In particular, we have discovered that uric acid is elevated in wound fluid, with
higher concentrations correlating with increased wound severity. We have also
revealed a corresponding depletion in uric acid precursors, including adenosine.
Further, we have revealed that xanthine oxidoreductase, the enzyme that catalyses
the production of uric acid, is present at elevated levels in wound fluid. Taken
together, these findings provide evidence that xanthine oxidoreductase may have a
function in the formation or persistence of chronic wounds. Here we describe the
potential function of xanthine oxidoreductase and uric acid accumulation in the
wound site, and the effect of xanthine oxidoreductase in potentiating the
inflammatory response.
PMID- 24357443
TI - Renal involvement in antiphospholipid syndrome.
AB - Renal involvement can be a serious problem for patients with antiphospholipid
syndrome (APS). However, this complication has been poorly recognized and
studied. It can be present in patients who have either primary or systemic lupus
erythematosus-associated APS. Clinical and laboratory features of renal
involvement in APS include hypertension, hematuria, acute renal failure, and
progressive chronic renal insufficiency with mild levels of proteinuria that can
progress to nephrotic-range proteinuria. The main lesions are renal artery
stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that
may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis,
arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar
occlusions, and focal cortical atrophy). APS can also cause end-stage renal
disease and allograft vascular thrombosis. This article reviews the range of
renal abnormalities associated with APS, and their diagnosis and treatment
options.
PMID- 24357444
TI - Role of modern imaging techniques in hand osteoarthritis research and clinical
practice.
AB - Hand osteoarthritis (OA) is a frequent disease, which may lead to considerable
pain and physical limitations. However, limited research has been performed in
hand OA. Lately, modern imaging techniques, such as ultrasonography (US) and
magnetic resonance imaging (MRI), have gained increasing attention in hand OA
clinical research. Both modalities may provide important knowledge about the
natural history and pathogenesis of the disease, in addition to serving as
potential outcome measures in clinical trials. In clinical practice, the
diagnosis of hand OA should be based on clinical examination and conventional
radiography, if necessary. However, US and MRI can provide information about the
degree of inflammation and exclude potential differential diagnoses.
PMID- 24357445
TI - The crystallization of monosodium urate.
AB - Gout is a common crystal-induced arthritis, in which monosodium urate (MSU)
crystals precipitate within joints and soft tissues and elicit an inflammatory
response. The causes of elevated serum urate and the inflammatory pathways
activated by MSU crystals have been well studied, but less is known about the
processes leading to crystal formation and growth. Uric acid, the final product
of purine metabolism, is a weak acid that circulates as the deprotonated urate
anion under physiologic conditions, and combines with sodium ions to form MSU.
MSU crystals are known to have a triclinic structure, in which stacked sheets of
purine rings form the needle-shaped crystals that are observed microscopically.
Exposed, charged crystal surfaces are thought to allow for interaction with
phospholipid membranes and serum factors, playing a role in the crystal-mediated
inflammatory response. While hyperuricemia is a clear risk factor for gout, local
factors have been hypothesized to play a role in crystal formation, such as
temperature, pH, mechanical stress, cartilage components, and other synovial and
serum factors. Interestingly, several studies suggest that MSU crystals may drive
the generation of crystal-specific antibodies that facilitate future MSU
crystallization. Here, we review MSU crystal biology, including a discussion of
crystal structure, effector function, and factors thought to play a role in
crystal formation. We also briefly compare MSU biology to that of uric acid
stones causing nephrolithasis, and consider the potential treatment implications
of MSU crystal biology.
PMID- 24357446
TI - Short term results of complete (D3) vs. standard (D2) mesenteric excision in
colon cancer shows improved outcome of complete mesenteric excision in patients
with TNM stages I-II.
AB - BACKGROUND: The aim of the present study was to investigate whether the new
method of complete mesocolic excision (CME) with a high (apical) vascular tie (D3
resection) had an immediate effect compared with a conventional (standard)
approach even in those patients without lymph node metastases. METHODS: A cohort
of 189 consecutive patients with tumour-nodal-metastasis (TNM) stages I-II and a
mean age of 73 years were operated on in the period from January 2007 to December
2008 in three community teaching hospitals. The CME approach (n = 89), used in
hospital A, was compared to the standard technique used (n = 105) in two other
hospitals, B and C. Lymph node yields from the specimens were used as a surrogate
measure of radical resections. Outcome was analysed after a median follow-up of
50.2 months. RESULTS: In-hospital mortality rate was 2.8 % in the CME group and
8.6 % in the standard group. The 3-year overall survival (OS) in the CME group
was 88.1 versus 79.0 % (p = 0.003) in the standard group, and the corresponding
disease-free survival (DFS) was 82.1 versus 74.3 % (p = 0.026). Cancer-specific
survival was 95.2 % in the CME group versus 90.5 % in the standard group (p =
0.067). Age, operative technique, and T category were significant in multiple Cox
regressions of OS and DFS. CONCLUSIONS: Compared with the standard (D2) approach,
introduction of CME surgical management of colon cancer resulted in a significant
immediate improvement of 3-year survival for patients with TNM stage I-II tumours
as assessed by OS and DFS.
PMID- 24357448
TI - Sex differences in pudendal somatosensory evoked potentials.
AB - BACKGROUND: Somatosensory evoked potentials (SEPs) of the pudendal nerve are a
well-established diagnostic tool for the evaluation of pelvic floor disorders.
However, the possible influence of sex differences on response latencies has not
been established yet. The aim of this study was to standardize the procedures and
to evaluate possible effects of gender differences on anal and penile/clitoral
SEPs. METHODS: The anal and dorsal penile/clitoral SEPs were recorded in 84
healthy subjects (40 males and 44 females; mean age 47.9 +/- 16.6 years, range 16
81 years; mean height 168.3 +/- 20.3 cm, range 155-187 cm). Pudendal SEPs were
evoked with a bipolar surface electrode stimulating the clitoris or the base of
the penis and the anal orifice and recorded using scalp electrodes. The latency
of the first positive component (P1) was measured. The effect and possible
interaction of (a) stimulation site and (b) gender on the two variables was
explored by multivariate analysis of variance (MANOVA). RESULTS: The examination
was well tolerated and a reproducible waveform of sufficient quality was obtained
in all the subjects examined. In the female subjects, a mean cortical P1 latency
of 37.0 +/- 2.6 and 36.4 +/- 3.2 ms for anal and clitoral stimulation,
respectively, was found. In the male subjects, the cortical latencies were 38.0
+/- 3.5 ms for the anal stimulation and 40.2 +/- 3.7 ms for the penile
stimulation. At MANOVA, a statistically significant main effect of stimulation
site and gender as well as a significant interaction between the two variables
was found. CONCLUSIONS: Anal and dorsal penile/clitoral SEPs represent a well
tolerated and reproducible method to assess the functional integrity of the
sensory pathways in male and female subjects. Obtaining sex-specific reference
data, by individual electrophysiological testing, is highly recommended because
of significant latency differences between males and females, at least as far as
penile/clitoral responses are concerned.
PMID- 24357449
TI - A contemporary review of venous adventitial cystic disease and three case
reports.
AB - Venous adventitial cystic disease is a rare vascular disease. The objective of
the study is to contemporarily review the literature of venous adventitial cystic
disease and report three other new cases of adventitial cystic disease in common
femoral vein. Articles published between 1947 and April 2013 were searched in
OVID and PubMed databases. The search yielded only 38 reported cases of venous
adventitial cystic disease. The general characteristics and disease management
information of the 41 cases (including our current 3 cases) were analyzed. Venous
adventitial cystic disease could develop late in life with an average age of
48.39 years (range, 5 to 77 years). Similar to arterial adventitial cystic
disease, venous adventitial cystic disease was also found to have a male
predominance (male to female ratio, 1.28:1). The common femoral vein was the most
likely vein to be involved (65.9%, 27 cases). Right and left sides were almost
equally affected. Extremity swelling (86.8%, 33 cases) was the main symptom of
patients presenting with venous adventitial cystic disease. Excision of cyst wall
in 30 patients (73.2%) was the main surgical procedure with a recurrence rate of
11.5%. Thirteen involved veins were resected; of which, 10 were reconstructed
with prosthetic or autologous graft. No recurrence was reported in these 13
patients. Postoperatively, nine cases received an anticoagulation therapy. In
conclusion, the etiology, treatment strategy, and outcomes of venous adventitial
cystic disease could not be well understood in the present review due to limited
numbers of cases. Studies with careful follow-up for at least up to first several
months are recommended.
PMID- 24357450
TI - Influence of perforating vein surgery in patients with venous ulceration.
AB - OBJECTIVES: The exact role of perforating vein surgery is still unclear. The aim
of this study is to analyze the influence of perforating vein surgery in patients
with venous ulceration. METHODS: This study was part of a randomized controlled
trial in which conservative and surgical treatment of venous ulceration was
compared. It is a secondary analysis of prospectively gathered data. Ninety-seven
active leg ulcers were surgically treated with a subfascial endoscopic
perforating vein surgery (SEPS) procedure. Concomitant superficial venous
incompetence was treated with flush saphenopopliteal ligation and/or
saphenofemoral ligation and limited stripping of the great saphenous vein. All
patients were also treated with ambulatory compression therapy. Ulcer healing and
recurrences are described in detail. To measure the completeness of the SEPS
procedure duplex ultrasonography was performed on each patient before and 6 weeks
and 12 months after surgery. Also newly formed perforators after surgery were
scored and their influence was analyzed. RESULTS: Analyses were performed on 94
ulcerated legs with a mean follow-up of 29 months. In all treated legs, only 45%
all perforators were treated. In 55% one (29%) or more (26%) perforators were
missed. Healing was not significantly influenced by the number of remaining
incompetent perforating veins, but recurrence was significantly higher in
patients who had incomplete SEPS procedure (p = 0.007 log-rank). New incompetent
perforating veins did not affect ulcer healing or recurrence. The plotted
location of new perforators did not show a pattern. Deep vein incompetence and
treatment of superficial venous incompetence had no significant influence on
healing or recurrence rates in a complete or incomplete SEPS procedure.
CONCLUSION: In this series a well-performed SEPS procedure lowers the venous
ulcer recurrence rate significantly, indicating the clinical importance of
incompetent perforating veins in patients with an active venous ulcer.
PMID- 24357451
TI - Optimal risk assessment of small-for-gestational-age fetuses using 31-34-week
biometry in a low-risk population.
AB - OBJECTIVE: To compare the performance of traditional growth charts for estimated
fetal weight (EFW) and a validated pragmatic probabilistic approach using
biometry at 31-34 weeks' gestation to screen for late pregnancy small-for
gestational age (SGA) fetuses in a low-risk population. METHODS: Records of
ultrasound biometry at 31-34 weeks were reviewed in 7755 consecutive low-risk
women between 2002 and 2011. Fetal malformations, Doppler anomalies and preterm
delivery before 37 weeks were excluded. SGA was defined by various percentile cut
offs of birth weight. The probability of SGA was modeled as a function of Z
scores of femur length, abdominal circumference and head circumference. The model
was validated on a second independent dataset of 1725 pregnancies from a
different screening unit. The screening performance of this probabilistic
approach was compared with those of traditional EFW growth charts. The additional
value of factoring in maternal characteristics was also ascertained. RESULTS:
Using national birth-weight charts, the proportions of newborns at 37-42 weeks
with birth weight<3(rd) , <5(th) and<10(th) centiles were 3%, 6% and 12%,
respectively, and there was a 2% rate of birth weight<2500 g. For a 10% false
positive rate, a direct probabilistic approach yielded a 51% detection rate of
neonates with birth weight<10(th) centile, compared to the 32% and 48% detection
rates given by the 10(th) centile cut-off of two reference charts for EFW. Adding
maternal characteristics significantly improved detection rate by 2% to 53%.
CONCLUSIONS: The suggested validated approach to screening for late SGA fetuses
outperforms traditional approaches using growth charts. By adding maternal
characteristics, this screening method offers a favorable alternative to
customized charts.
PMID- 24357452
TI - Breathing in a box: constraints on lung ventilation in giant pterosaurs.
AB - Pterosaurs were the first vertebrates to achieve active flight, with some derived
forms reaching enormous size. Accumulating fossil evidence confirms earlier
indications that selection for large size in these flying forms resulted in a
light, yet strong skeleton characterized by fusion of many bones of the trunk.
However, this process also added mechanical constraints on the mobility of the
thorax of large pterosaurs that likely limited the options available for lung
ventilation. We present an alternative hypothesis to recent suggestions of an
avian-like mechanism of costosternal pumping as the primary means of aspiration.
An analysis of the joints among the vertebrae, ribs, sternum, and pectoral girdle
of large pterosaurs indicates limited mobility of the ribcage and sternum.
Comparisons with modes of lung ventilation in extant amniotes suggests that the
stiffened thorax, coupled with mobile gastralia and prepubic bones, may be most
consistent with an extracostal mechanism for lung ventilation in large
pterodactyloids, perhaps similar to a crocodile-like visceral displacement
system.
PMID- 24357454
TI - The management of trauma in childhood and adolescence.
PMID- 24357453
TI - Struma ovarii: role of imaging?
AB - As clinical features in struma ovarii patients in the absence of thyrotoxicosis
are generally non-specific and resemble ovarian malignancy, preoperative
radiological diagnosis becomes all the more relevant in order to avoid ovarian
cancer type surgery (including bilateral salpingo-oophorectomy, hysterectomy,
omentectomy and occasionally appendectomy) for this usually benign and rare
ovarian mass. As struma ovarii is an uncommon entity, it is all the more
important to perform state-of-the-art magnetic resonance (MR) imaging, including
high-resolution imaging and diffusion-weighted imaging. The goal of this review
paper is to give an update of the key findings of both benign and malignant
struma ovarii and to present an unusual case of a purely cystic ovarian struma.
Key Points * Clinical features in struma ovarii are generally non-specific and
resemble ovarian malignancy.* Pre-operative radiological diagnosis is important
to avoid ovarian cancer type surgery (bilateral salpingo-oophorectomy,
hysterectomy, omentectomy and occasionally appendectomy).* State-of-the-art MR
imaging might help to characterise this unusual ovarian mass.* Struma ovarii can
occasionally present as a purely cystic lesion.* However, the role of imaging to
identify struma ovarii preoperatively remains limited.
PMID- 24357455
TI - An unusual cause of gross hematuria: questions and answers.
PMID- 24357456
TI - MicroRNA-198 inhibits proliferation and induces apoptosis of lung cancer cells
via targeting FGFR1.
AB - Lung cancer is the most common cause of death from cancer worldwide and recent
studies have revealed that microRNAs play critical roles to regulate lung
carcinogenesis. Here we present evidence to show the role of miR-198 in lung
cancer development. Our results showed that ectopic expression of miR-198
inhibits the viability and induces the apoptosis of human non-small cell lung
cancer cells A549 and NCI-H460, while miR-198 inhibition resulted in opposite
changes. In nude mice miR-198 inhibits A549 growth of tumor graft. We further
demonstrated that miR-198 directly targets fibroblast growth factor receptor 1
(FGFR1) in lung cancer cells. Restoring FGFR1 expression blocked the inhibitory
function of miR-198, while FGFR1 inhibition achieved the similar phenotypes of
miR-198 overexpression. Hence, our data delineates the molecular pathway by which
miR-198 inhibits lung cancer cellular proliferation and induces apoptosis, and
may have important implication for the treatment of lung carcinogenesis.
PMID- 24357457
TI - Radiofrequency (thermal) ablation versus no intervention or other interventions
for hepatocellular carcinoma.
AB - BACKGROUND: Hepatocellular carcinoma is the fifth most common cancer worldwide.
Percutaneous interventional therapies, such as radiofrequency (thermal) ablation
(RFA), have been developed for early hepatocellular carcinoma. RFA competes with
other interventional techniques such as percutaneous ethanol injection, surgical
resection, and liver transplantation. The potential benefits and harms of RFA
compared with placebo, no intervention, chemotherapy, hepatic resection, liver
transplantation, or other interventions are unclear. OBJECTIVES: To assess the
beneficial and harmful effects of RFA versus placebo, no intervention, or any
other therapeutic approach in patients with hepatocellular carcinoma. SEARCH
METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials
Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
EMBASE, and ISI Web of Science to September 2012. We handsearched meeting
abstracts from ASCO, ESMO, AASLD, EASL, APASL, and references of articles. We
also contacted researchers in the field (last search September 2012). SELECTION
CRITERIA: We considered for inclusion randomised clinical trials investigating
the effects of RFA versus placebo, no intervention, or any other therapeutic
approach on hepatocellular carcinoma patients regardless of blinding, language,
and publication status. DATA COLLECTION AND ANALYSIS: Two review authors
independently performed the selection of trials, assessment of risk of bias, and
data extraction. We contacted principal investigators for missing information. We
analysed hazard ratios (HR) as relevant effect measures for overall survival, two
year survival, event-free survival, and local recurrences with 95% confidence
intervals (CI). In addition, we analysed dichotomous survival outcomes using risk
ratios (RR). We used trial sequential analysis to control the risk of random
errors ('play of chance'). MAIN RESULTS: We identified no trials comparing RFA
versus placebo, no intervention, or liver transplantation. We identified and
included 11 randomised clinical trials with 1819 participants that included four
comparisons: RFA versus hepatic resection (three trials, 578 participants); RFA
versus percutaneous ethanol injection (six trials, 1088 participants) including
one three-armed trial that also investigated RFA versus acetic acid injection;
RFA versus microwave ablation (one trial, 72 participants); and RFA versus laser
ablation (one trial, 81 participants). Ten of the eleven included trials reported
on the primary outcome of this review, overall survival. Rates of major
complications or procedure-related deaths were reported in 10 trials. The overall
risk of bias was considered low in five trials and high in six trials. For a
subgroup analysis, we included only low risk of bias trials. Regarding the
comparison RFA versus hepatic resection, there was moderate-quality evidence from
two low risk of bias trials that hepatic resection seems more effective than RFA
regarding overall survival (HR 0.56; 95% CI 0.40 to 0.78) and two-year survival
(HR 0.38; 95% CI 0.17 to 0.84). However, if we included a third trial with high
risk of bias, the difference became insignificant (overall survival: HR 0.71; 95%
CI 0.44 to 1.15). With regards to the outcomes event-free survival and local
progression, hepatic resection also yielded better results than RFA. However, the
number of complications was higher in surgically treated participants (odds ratio
(OR) 8.24; 95% CI 2.12 to 31.95). RFA seemed superior to percutaneous ethanol or
acetic acid injection regarding overall survival (HR 1.64; 95% CI 1.31 to 2.07).
The RR for mortality was also in favour of RFA, but did not reach statistical
significance (150/490 (30.6%) people in the percutaneous ethanol or acetic acid
group versus 119/496 (24.0%) people in the RFA group; RR 1.76; 95% CI 0.97 to
3.22). The proportion of adverse events did not differ significantly between RFA
and percutaneous ethanol or acetic acid injection (HR 0.70; 95% CI 0.33 to 1.48).
Trial sequential analyses revealed that the number of participants in the
included trials was insufficient and that more trials are needed to assess the
effects of RFA versus other interventions. AUTHORS' CONCLUSIONS: The effects of
RFA versus no intervention, chemotherapeutic treatment, or liver transplantation
are unknown. We found moderate-quality evidence that hepatic resection is
superior to RFA regarding survival. However, RFA might be associated with fewer
complications and a shorter hospital stay than hepatic resection. We found
moderate-quality evidence showing that RFA seems superior to percutaneous ethanol
injection regarding survival. There were too sparse data to recommend or refute
ablation achieved by techniques other than RFA. More randomised clinical trials
with low risk of bias and low risks of random errors assessing the effect of RFA
are needed.
PMID- 24357458
TI - Sustained elevation of Snail promotes glial-mesenchymal transition after
irradiation in malignant glioma.
AB - BACKGROUND: Ionizing irradiation is an effective treatment for malignant glioma
(MG); however, a higher rate of recurrence with more aggressive phenotypes is a
vital issue. Although epithelial-mesenchymal transition (EMT) is involved in
irradiation-induced cancer progression, the role for such phenotypic transition
in MG remains unknown. METHODS: To investigate the mechanism of irradiation
dependent tumor progression in MG, we performed immunohistochemistry (IHC) and
qRT-PCR using primary and recurrent MG specimens, MG cell lines, and primary
culture cells of MG. siRNA technique was used for MG cell lines. RESULTS: In 22
cases of clinically recurrent MG, the expression of the mesenchymal markers
vimentin and CD44 was found to be increased by IHC. In paired identical MG of 7
patients, the expression of collagen, MMPs, and YKL-40 were also elevated in the
recurrent MGs, suggesting the The Cancer Genome Atlas-based mesenchymal subtype.
Among EMT regulators, sustained elevation of Snail was observed in MG cells at 21
days after irradiation. Cells exhibited an upregulation of migration, invasion,
numbers of focal adhesion, and MMP-2 production, and all of these mesenchymal
features were abrogated by Snail knockdown. Intriguingly, phosphorylation of
ERK1/2 and GSK-3beta were increased after irradiation in a Snail-dependent
manner, and TGF-beta was elevated in both fibroblasts and macrophages but not in
MG cells after irradiation. It was noteworthy that irradiated cells also
expressed stemness features such as SOX2 expression and tumor-forming potential
in vivo. CONCLUSIONS: We here propose a novel concept of glial-mesenchymal
transition after irradiation in which the sustained Snail expression plays an
essential role.
PMID- 24357460
TI - Carbaborane-substituted 1,2,3-triphospholanes and 1-aza-2,5-diphospholane: new
synthetic approaches.
AB - New phosphorus-containing, five-membered P,P,P and P,N,P heterocycles were
synthesized and fully characterized. The P,P,P heterocycles, 1,2,3
triphospholanes, can be synthesized by two different facile pathways, whereas the
P,N,P compound, a 1-aza-2,5-diphospholane, can only be obtained with silylamine.
PMID- 24357459
TI - A deletion causing NF2 exon 9 skipping is associated with familial autosomal
dominant intramedullary ependymoma.
AB - BACKGROUND: Intramedullary ependymomas are rare and benign tumors in the adult.
Little is known about their physiopathology, but the implication of the NF2 gene
is suspected because of their presence in a third of patients with type 2
neurofibromatosis (NF2), a disorder caused by mutation of the NF2 gene. METHODS:
We conducted a clinical and genetic study of a family in which 5 of 9 members
suffered from intramedullary ependymoma. Karyotyping and CGH array analysis were
performed on DNA from peripheral blood lymphocytes from affected participants.
The NF2 gene sequences were then determined in DNA from 3 nonaffected and all 5
affected members of the family. RESULTS: Karyotype and CGH array findings were
normal. Sequencing of NF2 revealed a heterozygous deletion, c.811-39_841del69bp,
at the intron 8/exon 9 junction, in all affected members that was absent from all
nonaffected members. RT-PCR analysis and sequencing revealed a novel NF2
transcript characterized by a skipping of exon 9 (75 bp). This deletion is
predicted to result in a 25-amino acid deletion in the N-terminal FERM domain of
neurofibromin 2. Modeling of this mutant domain suggests possible disorganization
of the subdomain C. CONCLUSION: We report the first family with an NF2 mutation
associated with intramedullary ependymomas without other features of NF2
syndrome. This mutation, which has not been described previously, may
particularly affect the function of neurofibromin 2 in ependymocytes leading to
the development of intramedullary WHO grade II ependymomas. We propose that
sporadic intramedullary ependymomas should also be analyzed for this region of
NF2 gene.
PMID- 24357461
TI - Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like
receptor 4 signaling in diabetic nephropathy.
AB - Dyslipidemia is an independent risk factor for the development and progression of
diabetic nephropathy (DN). In this review, we summarize mouse models with both
diabetes and dyslipidemia, and their associated complications. We then discuss
molecules potentially involved in deterioration of DN by dyslipidemia. We focus
especially upon toll-like receptor 4 (TLR4) and one of its endogenous ligands,
myeloid-related protein 8 (MRP8 or S100A8), since we have found that their mRNA
levels are commonly increased in glomeruli of type 1 (streptozotocin [STZ]
induced) and type 2 (A-ZIP/F-1 lipoatrophic) diabetic mice. Gene expression of
MRP8 and Tlr4 is further upregulated during worsening of STZ-induced DN by a high
fat diet (HFD). Moreover, these HFD-induced changes are accompanied by enhanced
gene expression of CCAAT element binding protein beta and phosphorylation of c
Jun N-terminal kinase in the kidney, which have also been reported in pancreatic
beta cells under diabetic-hyperlipidemic conditions. Effects of a HFD upon DN are
cancelled in Tlr4 knockout mice. Macrophages are the predominant source of MRP8
in glomeruli. In cultured macrophages, combinatorial treatment with high glucose
and palmitate amplifies MRP8 expression in a Tlr4-dependent manner, and
recombinant MRP8 protein markedly increases gene expression of the inflammatory
cytokines interleukin-1beta and tumor necrosis factor alpha. Here, we propose
'macrophage-mediated glucolipotoxicity' via activation of MRP8/TLR4 signaling as
a novel mechanism of pathophysiology for DN.
PMID- 24357462
TI - Tracheostomy in stroke patients.
AB - OPINION STATEMENT: Patients with severe ischemic and hemorrhagic stroke may
require tracheostomy in the course of their disease. This may apply to stroke
unit patients whose deficits include a severe dysphagia posing such risk of
aspiration as it cannot be sufficiently counteracted by tube feeding and
swallowing therapy alone. More often, however, tracheostomy is performed in
stroke patients so severely afflicted that they require intensive care unit
treatment and mechanical ventilation. In these, long-term ventilation and
prolonged insufficient airway protection are the main indications for
tracheostomy. Accepted advantages are less pharyngeal and laryngeal lesions than
with prolonged orotracheal intubation, better oral hygiene and nursing care, and
higher patient comfort. Optimal timing of tracheostomy is unclear, in general, as
in stroke intensive care unit patients. Potential benefits of early tracheostomy
concerning ventilation duration and length of stay, respirator weaning, airway
safety, rate of pneumonia, and other complications, outcome and mortality have
been suggested in studies on non-neurologic subgroups of critical care patients.
Stroke patients have hardly been investigated with regard to these aspects, and
mainly retrospectively. A single randomized pilot trial on early tracheostomy in
60 ventilated patients with severe hemorrhagic and ischemic stroke demonstrated
feasibility, safety, and less need of sedation. Regarding the technique, bedside
percutaneous dilational tracheostomy should be preferred over surgical
tracheostomy because of several reported advantages. As the procedural risk is
low and early tracheostomy does not seem to worsen the clinical course of the
ventilated stroke patient, it is reasonable to assess the need of further
ventilation at the end of the first week of intensive care and proceed to
tracheostomy if extubation is not feasible. Reliable prediction of prolonged
ventilation need and outcome benefits of early tracheostomy, however, await
further clarification. Decannulation of stroke patients after discontinued
ventilation has to follow reliable confirmation of swallowing ability, as by
endoscopy.
PMID- 24357463
TI - The Liverpool uveal melanoma liver metastases pathway: outcome following liver
resection.
AB - AIM: To determine the outcome of patients that underwent liver resection for
metastases from uveal melanoma. METHODS: Over a 9-year period, patients referred
with uveal melanoma metastases were included. Following treatment of primary
uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly
non-contrast liver magnetic resonance imaging (MRI) surveillance. Following
detection of liver metastases, patients were staged with a contrast-enhanced
(Primovist((r))) liver MRI, computer tomography (CT) of the thorax and staging
laparoscopy. RESULTS: 155 patients were referred with uveal melanoma liver
metastases, of which 17 (11.0%) patients had liver resection and one patient was
treated with percutaneous radio-frequency ablation. The majority of patients
undergoing liver resection were treated with multiple metastectomies (n = 8) and
three patients had major liver resections. The overall median survival for
patients treated with surgery/ablation was 27 (14-90) months, and this was
significantly better compared to patients treated palliatively [median = 8(1-30)
months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median
= 13(6-36) months]. Patients who had undergone a major liver resection had a
significantly poorer disease-free survival (P = 0.037). CONCLUSIONS: Patients who
can undergo surgical resection for metastatic uveal melanoma have a more
favorable survival compared to those who do not.
PMID- 24357464
TI - Interstitial deletion 14q22.3-q23.2: genotype-phenotype correlation.
AB - The increasing use of molecular tools in genetic diagnosis has produced a surge
in the detection of genomic imbalances. Among the growing number of newly
discovered chromosome alterations are the interstitial deletions 14q21-q23. In
previous reports of this deletion, the patients appear to share ocular defects,
pituitary alterations and hand/foot anomalies. Here, we present a 12-year-old
girl with dysmorphic face, choanal atresia, gastroesophageal reflux, and moderate
developmental delay, in whom an interstitial deletion 14q22.3-q23.2 was detected
using a 180k array comparative genome hybridization. The 6.5 Mb deletion contains
27 genes, including three genes of the SIX family: SIX1, SIX4, and SIX6. In
mammals, Six1 has been shown to be involved in ocular differentiation, whereas
Six4 and Six6 are primarily expressed in the hypothalamus, pituitary gland, and
facial bones. We used data on mouse embryos to evaluate the expression of the SIX
genes, as well as other representative genes lost in the current patient and a
previously published case with a similar phenotype, in order to correlate their
pattern of expression with the functional anomalies that constitute the patient's
phenotype. We also explored the possibility of other genetic influences, such as
the existence of an imprinted region in chromosome 14q, which may provide a
better understanding of the observed clinical variability.
PMID- 24357465
TI - Preparation and evaluation of PEO-coated materials for a microchannel
hemodialyzer.
AB - The marked increase in surface-to-volume ratio associated with microscale devices
for hemodialysis leads to problems with hemocompatibility and blood flow
distribution that are more challenging to manage than those encountered at the
conventional scale. In this work stable surface modifications with pendant
polyethylene oxide (PEO) chains were produced on polydimethylsiloxane (PDMS),
polycarbonate microchannel, and polyacrylonitrile membrane materials used in
construction of microchannel hemodialyzer test articles. PEO layers were prepared
by radiolytic grafting of PEO-polybutadiene-PEO (PEO-PB-PEO) triblock polymers to
the material surfaces. Protein repulsion was evaluated by measurement of surface
bound enzyme activity following contact of uncoated and PEO-coated surfaces with
beta-galactosidase. Protein adsorption was decreased on PEO-coated polycarbonate
and PDMS materials to about 20% of the level recorded on the uncoated materials.
Neither the triblocks nor the irradiation process was observed to have any effect
on protein interaction with the polyacrylonitrile membrane, or its permeability
to urea. This approach holds promise as a means for in situ application of safe,
efficacious coatings to microfluidic devices for blood processing that will
ensure good hemocompatibility and blood flow distribution, with no adverse
effects on mass transfer.
PMID- 24357466
TI - Osteological histology of the Pan-Alcidae (Aves, Charadriiformes): correlates of
wing-propelled diving and flightlessness.
AB - Although studies of osteological morphology, gross myology, myological histology,
neuroanatomy, and wing-scaling have all documented anatomical modifications
associated with wing-propelled diving, the osteohistological study of this highly
derived method of locomotion has been limited to penguins. Herein we present the
first osteohistological study of the derived forelimbs and hind limbs of wing
propelled diving Pan-Alcidae (Aves, Charadriiformes). In addition to detailing
differences between wing-propelled diving charadriiforms and nondiving
charadriiforms, microstructural modifications to the humeri, ulnae and femora of
extinct flightless pan-alcids are contrasted with those of volant alcids.
Histological thin-sections of four species of pan-alcids (Alca torda, ?Alca
grandis, ?Pinguinus impennis, ?Mancalla cedrosensis) and one outgroup
charadriiform (Stercorarius longicaudus) were compared. The forelimb bones of
wing-propelled diving charadriiforms were found to have significantly thicker
(~22%) cortical bone walls. Additionally, as in penguins, the forelimbs of
flightless pan-alcids are found to be osteosclerotic. However, unlike the pattern
documented in penguins that display thickened cortices in both forelimbs and hind
limbs, the forelimb and hind limb elements of pan-alcids display contrasting
microstructural morphologies with thickened forelimb cortices and relatively
thinner femoral cortices. Additionally, the identification of medullary bone in
the sampled ?Pinguinus impennis specimen suggests that further osteohistological
investigation could provide an answer to longstanding questions regarding sexual
dimorphism of Great Auks. Finally, these results suggest that it is possible to
discern volant from flightless wing-propelled divers from fragmentary fossil
remains.
PMID- 24357467
TI - Cognitive memory screening and referral program in community pharmacies in the
United States.
AB - INTRODUCTION: 12 chain community pharmacy sites located in two geographic areas
with the United States implemented easy-to-administer memory screening
assessments for patients with risk factors of cognitive memory decline and
referred at-risk patients to their physicians. AIM OF THE STUDY: To evaluate the
impact of a pharmacy-based cognitive memory screening and referral program,
measure patient satisfaction with these advanced clinical services, and assess
willingness to pay for cognitive memory screening services. SETTING: 12 chain
pharmacy sites located in two geographic areas--ten Fred Meyer Pharmacies located
in the Portland, Oregon area and two Kerr Drug Pharmacies located in North
Carolina. METHOD: Pharmacists were educated on Alzheimer's disease, trained on
how to provide cognitive memory screening exams, and equipped with screening and
documentation tools. Following each screening, pharmacist provided education and
counseling to the patients and referred at-risk patients to physicians for follow
up as appropriate. MAIN OUTCOME MEASURES: Results of screenings; satisfaction of
patients; willingness to pay. RESULTS: Pharmacists delivered cognitive memory
assessments to 161 patients from June to November 2008. 44.1 % of patients
experienced at least one cognitive deficiency that required referral to a
physician based on the screening conducted. The cognitive memory screening and
referral program was highly regarded by patients who completed the satisfaction
survey, with 98.4 % of respondents indicating that they were either very
satisfied or satisfied with the program. CONCLUSION: Cognitive memory screening
can be easily incorporated into clinical service offerings in community pharmacy
practice and provides a valuable opportunity to identify patients at-risk and
refer them to a physician for appropriate testing and diagnosis.
PMID- 24357468
TI - Synthesis and theoretical investigation of a 1,8
bis(bis(diisopropylamino)cyclopropeniminyl)naphthalene proton sponge derivative.
AB - We report herein the synthesis and characterization of a new proton sponge
derivative, 1,8-bis(bis(diisopropylamino)cyclopropeniminyl)naphthalene 4 (DACN),
as well as its bis-protonated counterpart 6. A crystal structure of 6 is
presented, along with variable temperature (1)H NMR data on the BF4(-) salt
(6?BF4). DFT calculations were performed to investigate the structure of the
monoprotonated species 7 and to gain insight into the structural and electronic
nature of all three species. The proton affinity (PA) of 4, calculated at the
B3LYP/6-311G++(d,p)//B3LYP/6-31G(d,p) level, taking into account thermal
corrections from the B3LYP/6-31G(d,p) method, was 282.3 kcal mol(-1), while its
pKa was estimated at 27.0. NICS calculations were performed to examine the
changes in aromaticity within these systems upon each successive protonation.
Lastly, homodesmotic reaction schemes were used in order to estimate the factors
contributing to the strong PA predicted for 4.
PMID- 24357469
TI - Flocculating Zymomonas mobilis is a promising host to be engineered for fuel
ethanol production from lignocellulosic biomass.
AB - Whereas Saccharomyces cerevisiae uses the Embden-Meyerhof-Parnas pathway to
metabolize glucose, Zymomonas mobilis uses the Entner-Doudoroff (ED) pathway.
Employing the ED pathway, 50% less ATP is produced, which could lead to less
biomass being accumulated during fermentation and an improved yield of ethanol.
Moreover, Z. mobilis cells, which have a high specific surface area, consume
glucose faster than S. cerevisiae, which could improve ethanol productivity. We
performed ethanol fermentations using these two species under comparable
conditions to validate these speculations. Increases of 3.5 and 3.3% in ethanol
yield, and 58.1 and 77.8% in ethanol productivity, were observed in ethanol
fermentations using Z. mobilis ZM4 in media containing ~100 and 200 g/L glucose,
respectively. Furthermore, ethanol fermentation bythe flocculating Z. mobilis
ZM401 was explored. Although no significant difference was observed in ethanol
yield and productivity, the flocculation of the bacterial species enabled biomass
recovery by cost-effective sedimentation, instead of centrifugation with
intensive capital investment and energy consumption. In addition, tolerance to
inhibitory byproducts released during biomass pretreatment, particularly acetic
acid and vanillin, was improved. These experimental results indicate that Z.
mobilis, particularly its flocculating strain, is superior to S. cerevisiae as a
host to be engineered for fuel ethanol production from lignocellulosic biomass.
PMID- 24357470
TI - Land-use conversion and changing soil carbon stocks in China's 'Grain-for-Green'
Program: a synthesis.
AB - The establishment of either forest or grassland on degraded cropland has been
proposed as an effective method for climate change mitigation because these land
use types can increase soil carbon (C) stocks. This paper synthesized 135 recent
publications (844 observations at 181 sites) focused on the conversion from
cropland to grassland, shrubland or forest in China, better known as the 'Grain
for-Green' Program to determine which factors were driving changes to soil
organic carbon (SOC). The results strongly indicate a positive impact of cropland
conversion on soil C stocks. The temporal pattern for soil C stock changes in the
0-100 cm soil layer showed an initial decrease in soil C during the early stage
(<5 years), and then an increase to net C gains (>5 years) coincident with
vegetation restoration. The rates of soil C change were higher in the surface
profile (0-20 cm) than in deeper soil (20-100 cm). Cropland converted to forest
(arbor) had the additional benefit of a slower but more persistent C
sequestration capacity than shrubland or grassland. Tree species played a
significant role in determining the rate of change in soil C stocks (conifer <
broadleaf, evergreen < deciduous forests). Restoration age was the main factor,
not temperature and precipitation, affecting soil C stock change after cropland
conversion with higher initial soil C stock sites having a negative effect on
soil C accumulation. Soil C sequestration significantly increased with
restoration age over the long-term, and therefore, the large scale of land-use
change under the 'Grain-for-Green' Program will significantly increase China's C
stocks.
PMID- 24357471
TI - Adrenalectomy for isolated metastasis from operable non-small-cell lung cancer.
AB - A best evidence topic in cardiothoracic surgery was written according to a
structured protocol. The question addressed was 'in [patients with isolated
adrenal metastasis from operable/operated non-small cell lung cancer] is
[adrenalectomy] superior [to chemo/radiotherapy alone for achieving long-term
survival]?' Altogether >160 papers were found using the reported search, of which
3 represented the best evidence to answer the clinical question. The authors,
journal, date and country of publication, patient group studied, study type,
relevant outcomes and results of these papers are tabulated. We conclude that the
body of evidence is small, retrospective and not formally controlled. As such
interpretation is limited by selection bias in assignment of patients. These
limitations notwithstanding, surgical resection is associated with prolonged
survival for patients with isolated adrenal metastasis from non-small cell lung
cancer (NSCLC). Patient selection is probably critical. Factors that are
important are: otherwise early tumour, node (TN) status of the lung primary and
R0 resection, long disease-free interval and confidence that there are no other
sites of metastasis. Patients with ipsilateral adrenal metastasis may derive the
greatest survival benefit from adrenalectomy, since spread to the ipsilateral
gland may occur via direct lymphatic channels in the retroperitoneum. Involvement
of the contralateral adrenal may signify haematogenous spread and therefore, a
more aggressive process. Adrenalectomy must be accompanied by regional lymph node
clearance to reduce the chance of further spread from the adrenal itself.
PMID- 24357473
TI - Protein intake protects against weight loss in healthy community-dwelling older
adults.
AB - Weight loss is prevalent in the elderly population, with deleterious health
consequences, notably loss of lean body mass and subsequent functional decline.
Protein intake below the current RDA [0.8 g/(kg . d)] is also common in older
adults; however, the link between the 2 has received little attention. Our
objective was to assess the relation between protein intake and incident 1-y
weight loss >=5% in community-dwelling older adults. We conducted a nested,
prospective, case-control study in 1793 community-living elderly participants of
the Quebec Longitudinal Study of Nutrition as a Determinant of Successful Aging
(NuAge). We studied 211 incident cases of 1-y weight loss (>=5%) and 211 weight
stable controls (+/-2%) matched by sex and age category (70 +/- 2, 75 +/- 2, and
80 +/- 2 y). Diet was measured by 3 nonconsecutive 24-h recalls. ORs (95% CIs)
for the association between protein intake and weight loss were computed by using
conditional logistic regression. After adjustment for body mass index, energy
intake, appetite, smoking status, physical activity level, physical function,
chronic diseases and medications, depressive symptoms, and serum albumin and
ultrasensitive C-reactive protein, the ORs of weight loss in participants with
low protein intakes [<0.8 g/(kg . d)] were 2.56 (95% CI: 1.01, 6.50) compared
with participants with very high protein intakes [>=1.2 g/(kg . d)].
Corresponding numbers were 2.15 (95% CI: 1.02, 4.56) in participants with
moderate protein intakes [0.8-<1.0 g/(kg . d)] and 1.33 (95% CI: 0.77, 2.28) in
participants with high protein intakes [1.0-1.2 g/(kg . d)]. Our results suggest
that protein intakes >1.0 g/(kg . d) are protective against weight loss in
healthy older adults. These findings add epidemiologic evidence in support of
higher optimal protein intakes than the current guidelines for healthy older
adults.
PMID- 24357472
TI - Effects of a screening and treatment protocol with haloperidol on post-cardiotomy
delirium: a prospective cohort study.
AB - OBJECTIVES: Post-cardiotomy delirium is common and associated with increased
morbidity and mortality. No gold standard exists for detecting delirium, and
evidence to support the choice of treatment is needed. Haloperidol is widely used
for treating delirium, but indication, doses and therapeutic targets vary.
Moreover, doubt has been raised regarding overall efficacy. The purpose of this
study was to assess the effect of a combination of early detection and
standardized treatment with haloperidol on post-cardiotomy delirium, with the
hypothesis that the proportion of delirium- and coma-free days could be
increased. Length of stay (LOS), complications and 180-day mortality are
reported. METHODS: Prospective interventional cohort study. One hundred and
seventeen adult patients undergoing cardiac surgery were included before
introduction of a screening and treatment protocol with haloperidol for delirium,
and 123 patients were included after. Nurses screened patients using validated
tools (the Delirium Observation Screening (DOS) scale and confusion assessment
method for the intensive care unit (CAM-ICU)). In case of delirium, a checklist
to eliminate precipitating/ inducing factors and a protocol for standardized
dosing with haloperidol was applied. Group comparison was done using non
parametric tests and analysis of fractions, and associations between delirium and
predefined covariates were analysed with logistic regression. RESULTS: Incidence
of delirium after cardiac surgery was 21 (14-29) and 22 (15-30) %, onset was on
postoperative day 1 (1-4) and 1 (1-3), duration was 1 (1-4) day and 3 (1-5) days,
respectively, with no significant difference (Period 1 vs 2, all values are given
as the median and 95% confidence interval). The proportion of delirium- and coma
free days was 67 (61-73) and 65 (60-70) %, respectively (ns). There was no
difference in LOS or complication rate. Delirium was associated to increasing
age, increased length of stay and complications. CONCLUSIONS: We observed no
increase in the proportion of delirium- and coma-free days after introduction of
a combination of early detection and standardized treatment with haloperidol on
post-cardiotomy delirium. Most patients were not severely affected, and the few
who were, proved difficult to treat, indicating that a simple treatment protocol
with haloperidol was ineffective.
PMID- 24357474
TI - ["Chances of a National Hand Trauma Center network"].
PMID- 24357475
TI - [Optimising care structures for severe hand trauma and replantation and chances
of launching a national network].
AB - Severe hand traumata have a significant impact on our health system and on
insurance companies, respectively. It is estimated that 33% of all occupational
injuries and 9% of all invalidity pensions are due to severe hand trauma.
Unfortunately, these high numbers are not only due to the severity of the trauma
but to organisational deficiencies. Usually, the patient is treated at the
general surgical emergency in the first place and only then forwarded to a
microsurgeon. This redirection increases the time that is required for the
patient to finally arrive at an expert for hand surgery. On the one hand, this
problem can be explained by the population's lack of awareness for distinguished
experts for hand and microsurgery, on the other hand, the emergency network, or
emergency doctors in particular are not well informed about where to take a
patient with a severe hand trauma - clearly a problem of communication between
the hospitals and the ambulance. It is possible to tackle this problem, but put
participating hand trauma centres have to work hand in hand as a network and thus
exploit synergy effects. The French system "FESUM" is a good example for such a
network and even comprises centres in Belgium and Switzerland. To improve the
treatment of severe hand trauma, a similar alliance was initiated in Germany just
recently. The pilot project "Hand Trauma Alliance" (www.handverletzung.com) was
started in April 2013 and currently comprises two hospitals within the region of
upper Bavaria. The network provides hand trauma replantation service on a 24/7
basis and aims at shortening the way from the accident site to the fully
qualified hand surgeon, to improve the therapy of severe hand injuries and to
optimise acute patient care in general. In order to further increase the
alliance's impact it is intended to extend the project's scope from regional to
national coverage - nevertheless, such an endeavour can only be done in
collaboration with the German Society for Hand Surgery (DGH). This article
comprises 2 parts. First, the state-of-the-art of acute severe hand trauma care
is summarised and explained. Subsequently, the above-mentioned pilot project is
described in every detail, including positive effects but also barriers that
still have to be overcome.
PMID- 24357476
TI - The role of the FESSH Hand Trauma Committee in Europe.
AB - In Europe the need for clear definitions of hand surgery facilities regarding
trauma is becoming really important to guarantee a correct and up-dated treatment
of lesions more and more frequent and complex. The goal for European patients
should be to have similar treatment based on appropriate referral and assistance
in centres officially accredited for hand surgery. The target for the European
countries, giving the correct support to the centres and surgeons treating these
problems, should also be to save the costs of residual invalidities. These are
some of the reasons for the European Federation of Societies for Surgery of the
Hand (FESSH) decided to form a committee (Hand Trauma Committee) devoted to study
this problem, trying to give common guidelines and forming an European net of
accredited centres. The first step was to collect data through a network of
national representatives. Covering a 487 millions population, 309 centres were
recorded, including 1 797 surgeons and 20 363 patients treated during January
2006, then having a clear situation of hand trauma treatment through Europe.
Next, the HTC worked on 3 definitions: hand trauma, hand trauma surgeons and hand
trauma centres and started to accredit centres applying to these well defined
criteria. The HTC is now working on scientific consensus on some traumatic
lesions but also on the important topic of prevention of hand traumas. This work
is expected to improve an homogenous situation throughout Europe focusing on the
better use of the given resources for the prevention and the treatment of these
traumatic lesions.
PMID- 24357477
TI - Experience of a national campaign for hand trauma prevention in France.
AB - INTRODUCTION: In France, hand injuries are the number one cause of all accidents
referred to our hospital casualty departments. Their human and economic
consequences are very serious. Two thirds of these accidents arise during
everyday living activities and a third of them happen at work. The specific
prevention of hand injuries in each of these domains has not been sufficiently
developed. The authors present the national prevention campaign recently set up
by the FESUM. MATERIALS AND METHODS: The campaign took place in the form of
events held in different towns in France. Each event, lasting from a minimum of 2
days to 10 days maximum, included press conferences, prevention workshops
specific to hand injuries, theatrical animation for youngsters, conferences for
the general public, meetings in industrial or training college environments,
photography and video exhibitions, and the publication of pamphlets and posters.
These manifestations were carried out in partnership with the association APAVC
and the voluntary involvement of surgeons from the FESUM hand centres in each
town visited. RESULTS: Over a period of 2 years, 22 large or medium-sized towns
were able to hold these campaign events. By this means, thousands of people -
adults, schoolchildren or young, professional apprentices - were made aware of
hand injuries and how to prevent them. We were able to reinforce the broadcasting
of simple prevention messages launched by the campaign, particularly with regard
to wearing gloves for all manual activities, with the help of heavy local,
regional and national media coverage. CONCLUSION: This campaign was the first
widespread action of its kind, aimed specifically at the prevention of hand
injuries. Furthermore, it was a way of strengthening the credibility of the FESUM
hand emergency centres with the health authorities and to promote the services
available to patients.
PMID- 24357478
TI - [Prevention of hand injuries - current situation in Europe].
AB - Hand injuries are a frequent occurrence and account for 41% of all occupational
injuries. In general such accidents are the result of stress, inattention,
tiredness, use of defective or poorly maintained machinery. However, artention
must equally be directed at the large number of accidents occurring in leisure
time activities since the inability to work due to a leisure time accident is
similarly cost-intensive. Throughout Europe attempts have been made in the past
10 years to improve prevention. At the initiative of the Hand Trauma Committee
(HTC) of FESSH prevention conferences were stated in 2009. These have in part
reduced the number of hand injuries in -Europe. In Austria a special controlling
committee was founded by the Austrian Workers' Compensation Board (AUVA) with the
specific objective of reducing the number of hand injuries. Similarly the "Circle
for Leisure Time Hand Injury Prevention" was created to specifically deal with
hand injuries occurring during leisure time activities. Through the cooperation
of these 2 committees and implementation of the thus decided measures, a
reduction in the number of accidents involving the hand is to be expected with a
concomitant reduction in the associated costs.
PMID- 24357479
TI - [Hand replantation: differences in functional outcome considering patient age and
sociomedical aspects].
AB - By presenting 2 cases of successful hand replantation with similar trauma
mechanism, level of amputation and ischaemia time of an 18-year-old female
patient and a 48-year-old depressive male patient, the influence of age and
sociomedical status on the postoperative outcome is discussed. DASH-
(disabilities of the arm, shoulder and hand) score and Biometrics E-LINK power
and sensitivity measurement were used to evaluate the outcomes.
PMID- 24357480
TI - [Economic profit of different injuries in a centre for hand surgery -
replantation vs. amputation].
AB - INTRODUCTION: The Institute for Reimbursements in Hospital (InEK) annually
provides an updated DRG system to ensure the medical service providers with a
cost-covering remunera-tion. However, the underlying cost data are often opaque
and disclosure of the basis of calculation does not take place. On the basis of
cost and revenue data from our clinic between 2010 and 2012, a profit statement
for amputations and replantation of one or more fingers was employed and compared
with the nationwide data of the calculation clinics. MATERIALS AND METHODS:
Inpatient days, the revenue and the costs incurred in our clinic based on the
cost matrix of InEK costing manual [4] were determined for amputation (DRG X05B),
replantation of one (DRG X07B) and several fingers (DRG X07A). The profit was
calculated as the difference between revenues and costs. Further-more, a
comparison of our data with the nationwide data of InEK was applied. RESULTS: For
each of the 3 DRGs the actual costs in our clinic were higher than the costs
generated by InEK. Only amputation appeared profitable, while all limb-preserving
interventions were associated with losses for our hospital. There was a clear
discrepancy between the data of cost of InEK GmbH to the data of our clinic.
CONCLUSION: In order not to create any monetary disincentives at the expense of
quality of care of individual patients, a cost-covering patient care for all case
groups mentioned above should be ensured. The general distrust in the InEK's data
that results from such a discrepancy in the cost data can only be rebutted by
increasing transparency and disclosure of the calculation basis.
PMID- 24357481
TI - [Compliance with ethical and professional guidelines in aesthetic surgery - a
task for institutional or national control?].
AB - In the future medicine will become more and more involved in fields that are not
principally concerned with curing illnesses. Against the background of an
obviously increasing demand for aesthetic interventions, questions arise
concerning the self-assessment of the physician and his/her ethical behaviour in
this segment of medical services. The necessary rules of behaviour have
frequently been formulated, in particular by the professional societies. In the
meantime the German chamber of physicians has established ethically founded
requirements on the basis of professionalism. These and the therein formulated
principles of medical responsibility provide a solid foundation for the ethically
justifiable and quality assured performance of aesthetic surgical interventions.
PMID- 24357482
TI - [Ethnic rhinoplasty - type changing or type preserving?].
AB - INTRODUCTION: We observe an annual augmentation of rhinoplasties to patients with
migration background. This article illustrates the special features of the design
and procedure of the operation considering the ethnic factors. METHODS: We
present a review of patients with Middle Eastern origin, their nasal
characteristics, their psychological specificities, specific expectations and
some surgical concepts referring to a selective literature review. RESULTS: The
Middle Eastern nose with a few exceptions offers a combination of specific
characteristics. This requires detailed discussions and a thorough preoperative
evaluation. More-over, both the psychological specificities and the expectations
of patients should not be disregarded. The treatment of patients with a Middle
Eastern background requires a particular empathy. In addition to the anatomic
characteristics, expectations, role models and the ethnic behaviour in the pre-
and postoperative period must all be considered. In the expectations of the
patients the surgeons should be familiar with the Middle Eastern role models. The
possibilities and the surgical limits can be discussed in detail with the patient
and unrealistic expectations should be avoided. CONCLUSION: The increased mix of
ethnic groups requires a new approach to aesthetic rhinoplasty, which aims
primarily to provide individual solutions. Middle Eastern noses represent one of
the most demanding challenges in rhinoplasty which lead to dramatic changes and
to deeply grateful patients for which a lot of experience is required. Therefore
the surgeon has to be highly specialised in Middle Eastern Nose rhinoplasty.
PMID- 24357483
TI - [Microvascular surgery fellowship at the Department of Plastic and Reconstructive
Surgery, Chang Gung Memorial University Hospital, Taipei-Linkou, Taiwan].
PMID- 24357484
TI - [Report from the annual meeting 2013 in Dusseldorf].
PMID- 24357488
TI - Impact of 900 MHz electromagnetic field exposure on main male reproductive
hormone levels: a Rattus norvegicus model.
AB - This work analyzes the effects of radiofrequency-electromagnetic field (RF-EMF)
exposure on the reproductive system of male rats, assessed by measuring
circulating levels of FSH, LH, inhibin B, activin B, prolactin, and testosterone.
Twenty adult male Sprague-Dawley rats (180 +/- 10 g) were exposed to 900 MHz RF
EMF in four equal separated groups. The duration of exposure was 1, 2, and 4
h/day over a period of 30 days and sham-exposed animals were kept under the same
environmental conditions as the exposed group except with no RF-EMF exposure.
Before the exposure, at 15 and 30 days of exposure, determination of the
abovementioned hormone levels was performed using ELISA. At the end of the
experiment, FSH and LH values of the long time exposure (LTE) group were
significantly higher than the sham-exposed group (p < 0.05). Serum activin B and
prolactin in the LTE group showed significant increase and inhibin B showed
significant decrease than sham and short time exposed (STE) groups after 30 days
RF-EMF exposure (p < 0.05). Also, a significant decrease in serum testosterone
levels in the LTE group was found compared to short and moderate time exposed
(MTE) groups after 30 days RF-EMF exposure (p < 0.05). Results suggest that
reproductive hormone levels are disturbed as a result of RF-EMF exposure and it
may possibly affect reproductive functions. However, testosterone and inhibin B
concentrations as a fertility marker and spermatogenesis were decreased
significantly.
PMID- 24357489
TI - Assessment of body mapping sportswear using a manikin operated in constant
temperature mode and thermoregulatory model control mode.
AB - Regional sweating patterns and body surface temperature differences exist between
genders. Traditional sportswear made from one material and/or one fabric
structure has a limited ability to provide athletes sufficient local wear
comfort. Body mapping sportswear consists of one piece of multiple knit structure
fabric or of different fabric pieces that may provide athletes better wear
comfort. In this study, the 'modular' body mapping sportswear was designed and
subsequently assessed on a 'Newton' type sweating manikin that operated in both
constant temperature mode and thermophysiological model control mode. The
performance of the modular body mapping sportswear kit and commercial products
were also compared. The results demonstrated that such a modular body mapping
sportswear kit can meet multiple wear/thermal comfort requirements in various
environmental conditions. All body mapping clothing (BMC) presented limited
global thermophysiological benefits for the wearers. Nevertheless, BMC showed
evident improvements in adjusting local body heat exchanges and local thermal
sensations.
PMID- 24357490
TI - Analysis of photosynthetically active radiation under various sky conditions in
Wuhan, Central China.
AB - Observations of photosynthetically active radiation (PAR) and global solar
radiation (G) at Wuhan, Central China during 2005-2012 were first reported to
investigate PAR variability at different time scales and its PAR fraction (F(p))
under different sky conditions. Both G irradiances (I(g)) and PAR irradiances
(I(p)) showed similar seasonal features that peaked in values at noon during
summer and reached their lower values in winter. F(p) reached higher values
during either sunrise or sunset; lower values of F p appeared at local noon
because of the absorption effects of water vapor and clouds on long-wave
radiation. There was an inverse relationship between clearness index (K(t)) and
F(p); the maximum I(p) decreased by 22.3 % (39.7 %) when sky conditions changed
from overcast to cloudless in summer (winter); solar radiation was more affected
by cloudiness than the seasonal variation in cloudy skies when compared with that
in clear skies. The maximum daily PAR irradiation (R(p)) was 11.89 MJ m-2 day-1
with an annual average of 4.85 MJ m-2 day-1. F p was in the range of 29-61.5 %
with annual daily average value being about 42 %. Meanwhile, hourly, daily, and
monthly relationships between R p and G irradiation (R g) under different sky
conditions were investigated. It was discovered that cloudy skies were the
dominated sky condition in this region. Finally, a clear-sky PAR model was
developed by analyzing the dependence of PAR irradiances on optical air mass
under various sky conditions for the whole study period in Central China, which
will lay foundations for ecological process study in the near future.
PMID- 24357491
TI - Development of personal pollen information-the next generation of pollen
information and a step forward for hay fever sufferers.
AB - Pollen allergies affect a large part of the European population and are
considered likely to increase. User feedback indicates that there are
difficulties in providing proper information and valid forecasts using
traditional methods of aerobiology due to a variety of factors. Allergen content,
pollen loads, and pollen allergy symptoms vary per region and year. The first
steps in challenging such issues have already been undertaken. A personalized
pollen-related symptom forecast is thought to be a possible answer. However,
attempts made thus far have not led to an improvement in daily forecasting
procedures. This study describes a model that was launched in 2013 in Austria to
provide the first available personal pollen information. This system includes
innovative forecast models using bi-hourly pollen data, traditional pollen
forecasts based on historical data, meteorological data, and recent symptom data
from the patient's hayfever diary. Furthermore, it calculates the personal
symptom load in real time, in particular, the entries of the previous 5 days, to
classify users. The personal pollen information was made available in Austria on
the Austrian pollen information website and via a mobile pollen application,
described herein for the first time. It is supposed that the inclusion of
personal symptoms will lead to major improvements in pollen information
concerning hay fever sufferers.
PMID- 24357493
TI - Dysspondyloenchondromatosis without COL2A1 mutation: possible genetic
heterogeneity.
AB - Dysspondyloenchondromatosis is a rare form of generalized enchondromatosis
associated with spinal involvement. This skeletal dysplasia is characterized by
multiple enchondromas present in vertebrae as well as in metaphyseal and
diaphyseal parts of the long tubular bones, post-natal short stature, and early
development of kyphoscoliosis. A novel heterozygous missense mutation in COL2A1
was recently identified in a patient with dysspondyloenchondromatosis. This
suggests that dysspondyloenchondromatosis might expand the already broad spectrum
of type II collagenopathies. Here, we report on a young girl with features of
dysspondyloenchondromatosis, specifically short stature, thoracoscoliosis, and
generalized enchondromas lesions. Sanger sequencing failed to detect a mutation
in COL2A1. We therefore suggest that dysspondyloenchondromatosis is a genetically
heterogeneous condition.
PMID- 24357492
TI - Increased dosage of RAB39B affects neuronal development and could explain the
cognitive impairment in male patients with distal Xq28 copy number gains.
AB - Copy number gains at Xq28 are a frequent cause of X-linked intellectual
disability (XLID). Here, we report on a recurrent 0.5 Mb tandem copy number gain
at distal Xq28 not including MECP2, in four male patients with nonsyndromic mild
ID and behavioral problems. The genomic region is duplicated in two families and
triplicated in a third reflected by more distinctive clinical features. The X
inactivation patterns in carrier females correspond well with their clinical
symptoms. Our mapping data confirm that this recurrent gain is likely mediated by
nonallelic homologous recombination between two directly oriented Int22h repeats.
The affected region harbors eight genes of which RAB39B encoding a small GTPase,
was the prime candidate since loss-of-function mutations had been linked to ID.
RAB39B is expressed at stable levels in lymphocytes from control individuals,
suggesting a tight regulation. mRNA levels in our patients were almost two-fold
increased. Overexpression of Rab39b in mouse primary hippocampal neurons
demonstrated a significant decrease in neuronal branching as well as in the
number of synapses when compared with the control neurons. Taken together, we
provide evidence that the increased dosage of RAB39B causes a disturbed neuronal
development leading to cognitive impairment in patients with this recurrent copy
number gain.
PMID- 24357494
TI - External validation of the OHTS-EGPS model for predicting the 5-year risk of open
angle glaucoma in ocular hypertensives.
AB - AIMS: To independently evaluate and compare the performance of the Ocular
Hypertension Treatment Study-European Glaucoma Prevention Study (OHTS-EGPS)
prediction equation for estimating the 5-year risk of open-angle glaucoma (OAG)
in four cohorts of adults with ocular hypertension. METHODS: Data from two
randomised controlled trials and two observational studies were analysed
individually to assess transferability of the prediction equation between
different geographical locations and settings. To make best use of the data and
to avoid bias, missing predictor values were imputed using multivariate
imputation by chained equations. Using the OHTS-EGPS risk prediction equation,
predicted risk was calculated for each patient in each cohort. We used the c
index, calibration plot and calibration slope to evaluate predictive ability of
the equation. RESULTS: Analyses were based on 393, 298, 188 and 159 patients for
the Rotterdam, Moorfields, Dunfermline, and Nottingham cohorts, respectively. The
discriminative ability was good, with c-indices between 0.69 and 0.83. In
calibration analyses, the risk of OAG was generally overestimated, although for
the Rotterdam cohort the calibration slope was close to 1 (1.09, 95% CI 0.72 to
1.46), the ideal value when there is perfect agreement between predicted and
observed risks. CONCLUSIONS: The OHTS-EGPS risk prediction equation has
predictive utility, but further validation in a population-based setting is
needed.
PMID- 24357495
TI - Anatomical and visual outcomes following ocriplasmin treatment for symptomatic
vitreomacular traction syndrome.
AB - OBJECTIVE: To evaluate the anatomical and visual outcomes of patients treated
with ocriplasmin for the treatment of symptomatic vitreomacular adhesion (sVMA),
including vitreomacular traction syndrome and macular holes. DESIGN:
Retrospective, interventional, single centre, case series. PARTICIPANTS: Patients
with sVMA. INTERVENTION: Patients were treated with a single intravitreal
injection of 0.125 mg ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis
EU) with the reconstitution technique recommended by the manufacturer. MAIN
OUTCOME MEASURES: The primary study endpoint was the resolution of sVMA by
spectral domain optical coherence tomography (SDOCT) at day 28. Secondary outcome
measures included time to vitreous release, visual acuity (VA), changes in the
optical coherence tomography (OCT) thickness and structure and macular hole
closure rate. RESULTS: 17 patients were included in the study and resolution of
vitreomacular adhesion (VMA) was verified by SDOCT in eight patients by day 28
(overall response rate of 47.1%, 8/17 eyes) with most patients experiencing VMA
release by 7 days (41.2%, 7/17 eyes). Those who did not have VMA resolution
showed no statistically significant change in VMA diameter as measured by
horizontal and vertical 5-line raster scans at final follow-up (p=0.82 and
p=0.75, respectively). The mean baseline Snellen VA was 20/49 and at final follow
up was 20/46 (p=0.59). The average central subfield thickness was 371 microns
prior to treatment and 324 microns at final follow-up (range 191-767 microns,
p=0.25). Patients meeting three of four positive predictors criteria (eg, no
epiretinal membrane (ERM) at baseline, VMA diameter <=1500 um and phakic lens
status) showed a response rate of 50.0% (seven of 14 patients); those meeting all
four criteria (eg, younger than 65, no ERM at baseline, VMA diameter <=1500 um
and phakic lens status) showed a response rate of 75.0% (three of four eyes).
Transient outer segment ellipsoid zone loss was documented in seven patients and
subretinal fluid presence following injection was noted in five patients. Four of
the five patients with macular holes at baseline experienced resolution of their
macular hole after injection. CONCLUSIONS: This is the first study to quantify
the extent of outer retinal changes seen in patients receiving ocriplasmin. Our
initial experience with ocriplasmin shows a significant anatomical effect and is
accompanied by transient changes in the outer retinal structures visualised by
SDOCT.
PMID- 24357496
TI - Ophthalmic statistics note 1: unit of analysis.
PMID- 24357497
TI - OCT for glaucoma diagnosis, screening and detection of glaucoma progression.
AB - Optical coherence tomography (OCT) is a commonly used imaging modality in the
evaluation of glaucomatous damage. The commercially available spectral domain
(SD)-OCT offers benefits in glaucoma assessment over the earlier generation of
time domain-OCT due to increased axial resolution, faster scanning speeds and has
been reported to have improved reproducibility but similar diagnostic accuracy.
The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible
registration, and advanced segmentation algorithms of macular and optic nerve
head regions. A review of the evidence to date suggests that retinal nerve fibre
layer remains the dominant parameter for glaucoma diagnosis and detection of
progression while initial studies of macular and optic nerve head parameters have
shown promising results. SD-OCT still currently lacks the diagnostic performance
for glaucoma screening.
PMID- 24357499
TI - Technique: imaging earliest tooth development in 3D using a silver-based tissue
contrast agent.
AB - Looking in microscopic detail at the 3D organization of initiating teeth within
the embryonic jaw has long-proved technologically challenging because of the
radio-translucency of these tiny un-mineralized oral tissues. Yet 3D image data
showing changes in the physical relationships among developing tooth and jaw
tissues are vital to understand the coordinated morphogenesis of vertebrate teeth
and jaws as an animal grows and as species evolve. Here, we present a new
synchrotron-based scanning solution to image odontogenesis in 3D and in
histological detail using a silver-based contrast agent. We stained fixed, intact
wild-type mice aged embryonic (E) day 10 to birth with 1% Protargol-S at 37
degrees C for 12-32 hr. Specimens were scanned at 4-10 um pixel size at 28 keV,
just above the silver K-edge, using micro-computed tomography (uCT) at the
Canadian Light Source synchrotron. Synchrotron uCT scans of silver-stained
embryos showed even the earliest visible stages of tooth initiation, as well as
many other tissue types and structures, in histological detail. Silver stain
penetration was optimal for imaging structures in intact embryos E15 and younger.
This silver stain method offers a powerful yet straightforward approach to
visualize at high-resolution and in 3D the earliest stages of odontogenesis in
situ, and demonstrates the important of studying the tooth organ in all three
planes of view.
PMID- 24357498
TI - A protocol for rheological characterization of hydrogels for tissue engineering
strategies.
AB - Hydrogels are studied extensively for many tissue engineering applications, and
their mechanical properties influence both cellular and tissue compatibility.
However, it is difficult to compare the mechanical properties of hydrogels
between studies due to a lack of continuity between rheological protocols. This
study outlines a straightforward protocol to accurately determine hydrogel
equilibrium modulus and gelation time using a series of rheological tests. These
protocols are applied to several hydrogel systems used within tissue engineering
applications: agarose, collagen, fibrin, MatrigelTM, and methylcellulose. The
protocol is outlined in four steps: (1) Time sweep to determine the gelation time
of the hydrogel. (2) Strain sweep to determine the linear-viscoelastic region of
the hydrogel with respect to strain. (3) Frequency sweep to determine the linear
equilibrium modulus plateau of the hydrogel. (4) Time sweep with values obtained
from strain and frequency sweeps to accurately report the equilibrium moduli and
gelation time. Finally, the rheological characterization protocol was evaluated
using a composite MatrigelTM-methylcellulose hydrogel blend whose mechanical
properties were previously unknown. The protocol described herein provides a
standardized approach for proper analysis of hydrogel rheological properties.
PMID- 24357500
TI - Effect of elicitors and precursors on azadirachtin production in hairy root
culture of Azadirachta indica.
AB - The present study involved strategies for enhancement in in vitro azadirachtin
(commercially used biopesticide) production by hairy root cultivation of
Azadirachta indica. Improvement in the azadirachtin production via triggering its
biosynthetic pathway in plant cells was carried out by the exogenous addition of
precursors and elicitors in the growth medium. Among the different abiotic stress
inducers (Ag(+), Hg(+2), Co(+2), Cu(+2)) and signal molecules (methyl jasmonate
and salicylic acid) tested, salicylic acid at 15 mg l(-1) of concentration was
found to enhance the azadirachtin yield in the hairy roots to the maximum (up to
4.95 mg g(-1)). Similarly, among the different biotic elicitors tested (filter
sterilized fungal culture filtrates of Phoma herbarium, Alternaria alternata,
Myrothecium sp., Fusarium solani, Curvularia lunata, and Sclerotium rolfsii;
yeast extract; and yeast extract carbohydrate fraction), addition of filter
sterilized fungal culture filtrate of C. lunata (1 % v/v) resulted in maximum
azadirachtin yield enhancement in hairy root biomass (up to 7.1 mg g(-1)) with
respect to the control (3.3 mg g(-1)). Among all the biosynthetic precursors
studied (sodium acetate, cholesterol, squalene, isopentynyl pyrophosphate,
mavalonic acid lactone, and geranyl pyrophosphate), the overall azadirachtin
production (70.42 mg l(-1) in 25 days) was found to be the highest with
cholesterol (50 mg l(-1)) addition as an indirect precursor in the medium.
PMID- 24357501
TI - Electrophilic alkylations of vinylsilanes: a comparison of alpha- and beta-silyl
effects.
AB - Kinetics of the reactions of benzhydrylium ions (Aryl2CH(+)) with the
vinylsilanes H2C=C(CH3)(SiR3), H2C=C(Ph)(SiR3), and (E)-PhCH=CHSiMe3 have been
measured photometrically in dichloromethane solution at 20 degrees C. All
reactions follow second-order kinetics, and the second-order rate constants
correlate linearly with the electrophilicity parameters E of the benzhydrylium
ions, thus allowing us to include vinylsilanes in the benzhydrylium-based
nucleophilicity scale. The vinylsilane H2C=C(CH3)(SiMe3), which is attacked by
electrophiles at the CH2 group, reacts one order of magnitude faster than
propene, indicating that alpha-silyl-stabilization of the intermediate carbenium
ion is significantly weaker than alpha-methyl stabilization because H2C=C(CH3)2
is 10(3) times more reactive than propene. trans-beta-(Trimethylsilyl)styrene,
which is attacked by electrophiles at the silylated position, is even somewhat
less reactive than styrene, showing that the hyperconjugative stabilization of
the developing carbocation by the beta-silyl effect is not yet effective in the
transition state. As a result, replacement of vinylic hydrogen atoms by SiMe3
groups affect the nucleophilic reactivities of the corresponding C=C bonds only
slightly, and vinylsilanes are significantly less nucleophilic than structurally
related allylsilanes.
PMID- 24357502
TI - Microenvironment is involved in cellular response to hydrostatic pressures during
chondrogenesis of mesenchymal stem cells.
AB - Chondrocytes integrate numerous microenvironmental cues to mount physiologically
relevant differentiation responses, and the regulation of mechanical signaling in
chondrogenic differentiation is now coming into intensive focus. To facilitate
tissue-engineered chondrogenesis by mechanical strategy, a thorough understanding
about the interactional roles of chemical factors under mechanical stimuli in
regulating chondrogenesis is in great need. Therefore, this study attempts to
investigate the interaction of rat MSCs with their microenvironment by imposing
dynamic and static hydrostatic pressure through modulating gaseous tension above
the culture medium. Under dynamic pressure, chemical parameters (pH, pO2, and
pCO2) were kept in homeostasis. In contrast, pH was remarkably reduced due to
increased pCO2 under static pressure. MSCs under the dynamically pressured
microenvironment exhibited a strong accumulation of GAG within and outside the
alginate beads, while cells under the statically pressured environment lost newly
synthesized GAG into the medium with a speed higher than its production. In
addition, the synergic influence on expression of chondrogenic genes was more
persistent under dynamic pressure than that under static pressure. This temporal
contrast was similar to that of activation of endogenous TGF-beta1. Taken
altogether, it indicates that a loading strategy which can keep a homeostatic
chemical microenvironment is preferred, since it might sustain the stimulatory
effects of mechanical stimuli on chondrogenesis via activation of endogenous TGF
beta1.
PMID- 24357503
TI - Kinetic properties of carbohydrate-lectin interactions: FimH antagonists.
AB - The lectin FimH is terminally expressed on type 1 pili of uropathogenic
Escherichia coli (UPEC), which is the main cause of urinary tract infections
(UTIs). FimH enables bacterial adhesion to urothelial cells, the initial step of
infection. Various mannose derivatives have been shown to antagonize FimH and are
therefore considered to be promising therapeutic agents for the treatment of
UTIs. As part of the preclinical development process, when the kinetic properties
of FimH antagonists were examined by surface plasmon resonance, extremely low
dissociation rates (k(off)) were found, which is uncommon for carbohydrate-lectin
interactions. As a consequence, the corresponding half-lives (t1/2) of the FimH
antagonist complexes are above 3.6 h. For a therapeutic application, extended
t1/2 values are a prerequisite for success, since the target occupancy time
directly influences the in vivo drug efficacy. The long t1/2 value of the tested
FimH antagonists further confirms their drug-like properties and their high
therapeutic potential.
PMID- 24357504
TI - Cardiac compression by massive mediastinal haematoma due to bleeding from the
ectopic bronchial artery.
PMID- 24357505
TI - Myocardial rupture: asymptomatic cover-up.
PMID- 24357506
TI - Highly sensitive troponins knocking at the door of primary prevention.
PMID- 24357507
TI - Biomarkers and acute coronary syndromes: an update.
AB - Biomarkers complement clinical assessment and the 12-lead ECG in the diagnosis,
risk stratification, triage, and management of patients with suspected acute
coronary syndrome (ACS). While there is broad consensus that cardiac troponin
(cTn) I or T is the preferred biomarker in clinical practice, important
uncertainties remain regarding the value of high-sensitivity cTn assays, their
best clinical use including the most appropriate timing of serial measurements,
as well as the added value of other biomarkers reflecting and quantifying other
pathophysiological signals including copeptin and natriuretic peptides. This
review will address these aspects with a focus on the diagnostic application of
biomarkers, as they are associated with immediate therapeutic consequences. In
addition, this review will briefly highlight that increased diagnostic accuracy
offered by high-sensitivity cTn assays has contributed to improve our
understanding of the incidence, pathophysiology, and mortality of the two
distinct components currently summarized under the term ACS: acute myocardial
infarction and unstable angina.
PMID- 24357508
TI - Endothelial nitric oxide: protector of a healthy mind.
AB - Endothelial nitric oxide (NO) is generated by constitutively active endothelial
nitric oxide synthase (eNOS), an essential enzyme responsible for cardiovascular
homeostasis. Historically, endothelial NO was first recognized as a major
vasodilator involved in control of vasomotor function and local blood flow. In
this review, our attention is focused on the emerging role of endothelial NO in
linking cerebrovascular function with cognition. We will discuss the recognized
ability of endothelial NO to modulate processing of amyloid precursor protein
(APP), influence functional status of microglia, and affect cognitive function.
Existing evidence suggests that the loss of NO in cultured human cerebrovascular
endothelium causes increased expression of APP and beta-site APP-cleaving enzyme
1 (BACE1) thereby resulting in increased secretion of amyloid beta peptides
(Abeta1-40 and Abeta1-42). Furthermore, increased expression of APP and BACE1 as
well as increased production of Abeta peptides was detected in the cerebral
microvasculature and brain tissue of eNOS-deficient mice. Since Abeta peptides
are considered major cytotoxic molecules responsible for the pathogenesis of
Alzheimer's disease, these observations support the concept that a loss of
endothelial NO might significantly contribute to the initiation and progression
of cognitive decline. In addition, genetic inactivation of eNOS causes activation
of microglia and promotes a pro-inflammatory phenotype in the brain. Behavioural
analysis revealed that eNOS-deficient mice exhibit impaired cognitive performance
thereby indicating that selective loss of endothelial NO has a detrimental effect
on the function of neuronal cells. Together with findings from prior studies
demonstrating the ability of endothelial NO to affect synaptic plasticity,
mitochondrial biogenesis, and function of neuronal progenitor cells, it is
becoming apparent that the role of endothelial NO in the control of central
nervous system function is very complex. We propose that endothelial NO
represents the key molecule linking cerebrovascular and neuronal function.
PMID- 24357509
TI - Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in
the mouse.
AB - Orofacial clefts are among the commonest birth defects. Among many genetic
contributors to orofacial clefting, Interferon Regulatory Factor 6 (IRF6) is
unique since mutations in this gene cause Van der Woude (VWS), the most common
clefting syndrome. Furthermore, variants in IRF6 contribute to increased risk for
non-syndromic cleft lip and/or palate (NSCL/P). Our previous work shows that
individuals with either VWS or NSCL/P may have cerebral anomalies (larger
anterior, smaller posterior regions), and a smaller cerebellum. The objective of
this study was to test the hypothesis that disrupting Irf6 in the mouse will
result in quantitative brain changes similar to those reported for humans with
VWS and NSCL/P. Male mice heterozygous for Irf6 (Irf6(gt1/+); n = 9) and wild
type (Irf6(+/+) ; n = 6) mice at comparable age underwent a 4.7-T MRI scan to
obtain quantitative measures of cortical and subcortical brain structures. There
was no difference in total brain volume between groups. However, the frontal
cortex was enlarged in the Irf6(gt1/+) mice compared to that of wild types (P =
0.028) while the posterior cortex did not differ. In addition, the volume of the
cerebellum of Irf6(gt1/+) mice was decreased (P = 0.004). Mice that were
heterozygous for Irf6 showed a similar pattern of brain anomalies previously
reported in humans with VWS and NSCL/P. These structural differences were present
in the absence of overt oral clefts. These results support a role for IRF6 in
brain morphometry and provide evidence for a potential genetic link to abnormal
brain development in orofacial clefting.
PMID- 24357510
TI - Sexual function, activity, and satisfaction among women receiving maintenance
hemodialysis.
AB - BACKGROUND AND OBJECTIVES: Past studies that demonstrated that sexual dysfunction
is common among women receiving chronic hemodialysis did not distinguish sexual
dysfunction/difficulty from sexual inactivity. This study sought to differentiate
these in order to elucidate the prevalence of true "sexual dysfunction" in this
population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: As part of a clinical
trial of symptom management strategies in patients receiving chronic
hemodialysis, female sexual function was prospectively assessed monthly for 6
months and quarterly thereafter using the Female Sexual Function Index, to which
questions were added differentiating sexual dysfunction/difficulty from sexual
inactivity. Beginning in month 7, patients were asked three questions about
sexual activity, difficulty, and satisfaction monthly. RESULTS: Of the women
enrolled in the clinical trial,125 participants completed 1721 assessments
between 2009 and 2011. Scores on 574 of 643 (89%) quarterly Female Sexual
Function Index assessments were consistent with sexual dysfunction, due largely
to sexual inactivity, which was reported on 525 (82%) quarterly assessments. When
reported (n=1663), the most frequently described reasons for sexual inactivity
were lack of interest in sex (n=715; 43%) and lack of a partner (n=647; 39%), but
rarely sexual difficulty (n=36; 2%). When reported (n=1582), women were
moderately to very satisfied with their sexual life on 1020 (64%) assessments and
on 513 of 671 (76%) assessments in which lack of interest was cited as a reason
for sexual inactivity. Women indicated an interest in learning about the causes
of and treatment for sexual dysfunction on just 5% of all assessments.
CONCLUSIONS: Although many women receiving chronic hemodialysis are sexually
inactive, few describe sexual difficulty. Most, including those with a lack of
interest in sex, are satisfied with their sexual life and few wish to learn about
treatment options. These findings suggest that true sexual dysfunction is
uncommon in this population and that treatment opportunities are rare.
PMID- 24357511
TI - Sexual Inactivity among hemodialysis patients: the patients' perspective.
PMID- 24357512
TI - Gelatinase B (-1562C/T) polymorphism in tumor progression and invasion of breast
cancer.
AB - Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor
invasion and progression. MMP-9 is a member of the MMP family and is also known
as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic
activity against type IV collagen, a major component of the basement membrane.
Our study aims to examine the association of Gelatinase B (-1562C > T) promoter
polymorphism with breast cancer invasion and progression. The study involves 200
breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T
(rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase
chain reaction and gel electrophoresis. The genotypes were determined and
compared between patients and controls, and the influence of the polymorphism on
clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9
polymorphism was detected more frequently in breast cancer patients than controls
(p < 0.001). Our results suggest the clinical importance of MMP-9 gene
polymorphism (-1562C > T) in breast cancer patients. The study may also help in
identifying individuals at risk of developing breast cancer.
PMID- 24357513
TI - The variant interleukin 1f7 rs3811047 G>A was associated with a decreased risk of
gastric cardiac adenocarcinoma in a Chinese Han population.
AB - To investigate the association between gastric cardiac adenocarcinoma (GCA) and
six functional single nucleotide polymorphisms (SNPs) including interleukin 1A
(IL1A) rs1800587 C>T, IL1B rs16944 G>A, IL1f7 rs3811047 G>A, IL3 rs40401 C>T, IL3
rs2073506 G>A, and IL7Ralpha rs6897932 A>G. We performed a hospital-based case
control study to evaluate the genetic effects of these SNPs. A total of 243 GCA
cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex
SNPscan(TM) kit was used to determine the genotypes. The IL1f7 rs3811047 G>A
polymorphism was significantly associated with a decreased risk of GCA either in
the single locus analyses or the recessive genetic model. However, there was no
significant association between the other five SNPs and GCA risk. These results
elucidated that the functional polymorphism, IL1f7 rs3811047 G>A, might
contribute to GCA susceptibility. However, the statistical power of our study was
limited, large well-designed studies and further functional investigations are
needed to confirm our findings.
PMID- 24357514
TI - MicroRNA218 inhibits glioma migration and invasion via inhibiting glioma
associated oncogene homolog 1 expression at N terminus.
AB - Glioma is characterized by high invasion, migration and proliferation abilities.
However, the molecular mechanism that triggers the development and recurrence of
this tumor is also elusive. This study aims to investigate the biological
function and molecular mechanism of microRNA218 in glioma. Human glioma samples
were obtained and employed to investigate the correlation between microRNA218 and
glioma pathological grading. Glioma cell viability was detected by the cell
counting kit-8 (CCK-8) cell counting assay. Transwell assay and wound-healing
assay were employed to examine the migration and invasion of the glioma cells.
The mRNA transcription and protein expression of glioma-associated oncogene
homolog 1 (GLI1) were analyzed by quantitative RT-PCR and Western blot analysis,
respectively. Southwestern blot assay was utilized to explore the possible
interaction site of GLI1 and microRNA218. The results indicated that microRNA218
is significantly down-regulated in glioma samples and negatively correlated with
the pathological grading. The cell viability was significantly decreased, and
migration and invasion were significantly inhibited in microRNA218 treated cells,
compared with un-treated cells. GLI1 was discovered acting as a functional
downstream target of microRNA218, by which microRNA218 inhibited glioma cell
migration and invasion. Southwestern blot result showed that microRNA218 targeted
directly the N terminus of GLI1 molecular, and repressed the GLI1 expression in
U87MG cells. In conclusion, microRNA218 could reduce the invasion and migration,
and inhibit proliferation of glioma cells by suppressing the expression of GLI1
protein at the interacting with the N terminus.
PMID- 24357515
TI - Increase in VEGF secretion from human fibroblast cells by bioactive glass S53P4
to stimulate angiogenesis in bone.
AB - Bioactive glasses (BAGs) are being investigated for the repair and reconstruction
of bone defects, as they exhibit osteoconductive and osteostimulatory potential.
However, successful bone regeneration requires also the neovascularization of the
construct which is, among other factors, guided by vascular endothelial growth
factor (VEGF). In this study, BAG S53P4 (53% SiO2 , 23% Na2 O, 20% CaO, 4% P2 O5
) is investigated in relation to VEGF-release and response of fibroblast cells.
Human CD-18CO fibroblasts were cultivated in contact with different granules of
different sizes (0.5-0.8 mm, 1.0-2.0 mm, and 2.0-3.15 mm) and at different
concentrations (0-1 wt/vol % of BAG) for 72 h. The analysis of morphology
revealed no toxic effect for all granule sizes and concentrations. Compared with
the reference, lactate dehydrogenase-activity of CCD-18CO cells increased in
contact with BAG samples. The VEGF release from CCD-18CO fibroblasts cultured on
different granule sizes and at different concentrations after 72 h of incubation
was quantified. It was found that particles of 0.5-0.8 mm and 1.0-2.0 mm in size
enhanced VEGF release, whereas BAG particle sizes of 2.0-3.15 mm led to
inhibition of VEGF release. The results are relevant to understand the influence
of the particle size and concentration of BAG S53P4 on VEGF expression and
neovascularization.
PMID- 24357516
TI - Bus stops and pedestrian-motor vehicle collisions in Lima, Peru: a matched case
control study.
AB - OBJECTIVE: To evaluate the relationship between bus stop characteristics and
pedestrian-motor vehicle collisions. METHODS: This was a matched case-control
study where the units of study were pedestrian crossings in Lima, Peru. We
performed a random sample of 11 police commissaries in Lima, Peru. Data
collection occurred from February 2011 to September 2011. A total of 97
intersection cases representing 1134 collisions and 40 mid-block cases
representing 469 collisions that occurred between October 2010 and January 2011,
and their matched controls, were included. The main exposures assessed were
presence of a bus stop and specific bus stop characteristics. The main outcome
measure was occurrence of a pedestrian-motor vehicle collision. RESULTS:
Intersections with bus stops were three times more likely to have a pedestrian
vehicle collision (OR 3.28, 95% CI 1.53 to 7.03), relative to intersections
without bus stops. Formal and informal bus stops were associated with higher odds
of a collision at intersections (OR 6.23, 95% CI 1.76 to 22.0 and OR 2.98, 1.37
to 6.49). At mid-block sites, bus stops on a bus-dedicated transit lane were also
associated with collision risk (OR 2.36, 95% CI 1.02 to 5.42). All bus stops were
located prior to the intersection, contrary to practices in most high-income
countries. CONCLUSIONS: In urban Lima, the presence of a bus stop was associated
with a threefold increase in risk of a pedestrian collision. The highly
competitive environment among bus companies may provide an economic incentive for
risky practices, such as dropping off passengers in the middle of traffic and
jockeying for position with other buses. Bus stop placement should be considered
to improve pedestrian safety.
PMID- 24357517
TI - Early frameshift mutation in PIGA identified in a large XLID family without
neonatal lethality.
AB - The phosphatidylinositol glycan class A (PIGA) protein is a member of the
glycosylphosphatidylinositol anchor pathway. Germline mutations in PIGA located
at Xp22.2 are thought to be lethal in males. However, a nonsense mutation in the
last coding exon was recently described in two brothers with multiple congenital
anomalies-hypotonia-seizures syndrome 2 (MCAHS2) who survived through birth
likely because of the hypomorphic nature of the truncated protein, but died in
their first weeks of life. Here, we report on a frameshift mutation early in the
PIGA cDNA (c.76dupT; p.Y26Lfs*3) that cosegregates with the disease in a large
family diagnosed with a severe syndromic form of X-linked intellectual
disability. Unexpectedly, CD59 surface expression suggested the production of a
shorter PIGA protein with residual functionality. We provide evidence that the
second methionine at position 37 may be used for the translation of a 36 amino
acids shorter PIGA. Complementation assays confirmed that this shorter PIGA cDNA
was able to partially rescue the surface expression of CD59 in a PIGA-null cell
line. Taken together, our data strongly suggest that the early frameshift
mutation in PIGA produces a truncated hypomorph, which is sufficient to rescue
the lethality in males but not the MCAHS2-like phenotype.
PMID- 24357518
TI - The influence of local spring temperature variance on temperature sensitivity of
spring phenology.
AB - The impact of climate warming on the advancement of plant spring phenology has
been heavily investigated over the last decade and there exists great variability
among plants in their phenological sensitivity to temperature. However, few
studies have explicitly linked phenological sensitivity to local climate
variance. Here, we set out to test the hypothesis that the strength of
phenological sensitivity declines with increased local spring temperature
variance, by synthesizing results across ground observations. We assemble ground
based long-term (20-50 years) spring phenology database (PEP725 database) and the
corresponding climate dataset. We find a prevalent decline in the strength of
phenological sensitivity with increasing local spring temperature variance at the
species level from ground observations. It suggests that plants might be less
likely to track climatic warming at locations with larger local spring
temperature variance. This might be related to the possibility that the frost
risk could be higher in a larger local spring temperature variance and plants
adapt to avoid this risk by relying more on other cues (e.g., high chill
requirements, photoperiod) for spring phenology, thus suppressing phenological
responses to spring warming. This study illuminates that local spring temperature
variance is an understudied source in the study of phenological sensitivity and
highlight the necessity of incorporating this factor to improve the
predictability of plant responses to anthropogenic climate change in future
studies.
PMID- 24357519
TI - Measuring the modified early warning score and the Rothman index: advantages of
utilizing the electronic medical record in an early warning system.
AB - Early detection of an impending cardiac or pulmonary arrest is an important focus
for hospitals trying to improve quality of care. Unfortunately, all current early
warning systems suffer from high false-alarm rates. Most systems are based on the
Modified Early Warning Score (MEWS); 4 of its 5 inputs are vital signs. The
purpose of this study was to compare the accuracy of MEWS against the Rothman
Index (RI), a patient acuity score based upon summation of excess risk functions
that utilize additional data from the electronic medical record (EMR). MEWS and
RI scores were computed retrospectively for 32,472 patient visits. Nursing
assessments, a category of EMR inputs only used by the RI, showed sharp
differences 24 hours before death. Receiver operating characteristic curves for
24-hour mortality demonstrated superior RI performance with c-statistics, 0.82
and 0.93, respectively. At the point where MEWS triggers an alarm, we identified
the RI point corresponding to equal sensitivity and found the positive likelihood
ratio (LR+) for MEWS was 7.8, and for the RI was 16.9 with false alarms reduced
by 53%. At the RI point corresponding to equal LR+, the sensitivity for MEWS was
49% and 77% for RI, capturing 54% more of those patients who will die within 24
hours.
PMID- 24357522
TI - Maternal deprivation decelerates postnatal morphological lung development of F344
rats.
AB - Intensive medical care at premature born infants is often associated with
separation of neonates from their mothers. Here, early artificial prolonged
separation of rat pups from their dams (Maternal Deprivation, MD) was used to
study potential impact on morphological lung maturation. Furthermore, we
investigated the influence of an endogenous deficiency of the neuropeptide
cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be
partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to
a retardation of postnatal lung development, DPP4-dependendly. We used wild type
and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate
cage for 2 h, while the pups remained in the nest on their own. Morphological
lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21
were determined morphometrically. Maternally deprived wild types showed a
retarded postnatal lung development compared with untreated controls in both
substrains. During alveolarization, an increased thickness of alveolar septa and
a decreased surface of septa about 50% were found. At the end of the
morphological lung maturation, the surface of the alveolar septa was decreased at
about 25% and the septal thickness remained increased about 20%. The
proliferation rate was also decreased about 50% on day 14. However, the MD
induced effects were less pronounced in DPP4-deficient rats, due to a significant
deceleration already induced by DPP4-deficiency. Thus, MD as a model for
postnatal stress experience influences remarkably postnatal development of rats,
which is significantly modulated by the DPP4-system.
PMID- 24357520
TI - The sclerostin-independent bone anabolic activity of intermittent PTH treatment
is mediated by T-cell-produced Wnt10b.
AB - Both blunted osteocytic production of the Wnt inhibitor sclerostin (Scl) and
increased T-cell production of the Wnt ligand Wnt10b contribute to the bone
anabolic activity of intermittent parathyroid hormone (iPTH) treatment. However,
the relative contribution of these mechanisms is unknown. In this study, we
modeled the repressive effects of iPTH on Scl production in mice by treatment
with a neutralizing anti-Scl antibody (Scl-Ab) to determine the contribution of T
cell-produced Wnt10b to the Scl-independent modalities of action of iPTH. We
report that combined treatment with Scl-Ab and iPTH was more potent than either
iPTH or Scl-Ab alone in increasing stromal cell production of OPG,
osteoblastogenesis, osteoblast life span, bone turnover, bone mineral density,
and trabecular bone volume and structure in mice with T cells capable of
producing Wnt10b. In T-cell-null mice and mice lacking T-cell production of
Wnt10b, combined treatment increased bone turnover significantly more than iPTH
or Scl-Ab alone. However, in these mice, combined treatment with Scl-Ab and iPTH
was equally effective as Scl-Ab alone in increasing the osteoblastic pool, bone
volume, density, and structure. These findings demonstrate that the Scl
independent activity of iPTH on osteoblasts and bone mass is mediated by T-cell
produced Wnt10b. The data provide a proof of concept of a more potent therapeutic
effect of combined treatment with iPTH and Scl-Ab than either alone.
PMID- 24357523
TI - A colorimetric and ratiometric fluorescent probe for sulfite based on an
intramolecular cleavage mechanism.
AB - A colorimetric and ratiometric fluorescent sulfite probe, the levulinate of 4
hydroxynaphthalimide, was successfully synthesized from 4-hydroxy-naphthalimide
and levulinic acid. Through sulfite-mediated intramolecular cleavage, the probe
was converted into 4-hydroxynaphthalimide, which when excited at 450 nm,
displayed a large Stokes shift due to the intramolecular charge transfer process.
The probe exhibited high selectivity and sensitivity towards sulfite over other
typical anionic species (F(-), Cl(-), Br(-), I(-), HPO(4)(2-), SO(4)(2-), NO(3)(
), AcO(-), ClO(4)(-), HCO(3)(-)) in HEPES-buffered solution (25 mm, pH 7.4, 50%
acetonitrile, v/v).
PMID- 24357524
TI - OA10 is a novel p38alpha mitogen-activated protein kinase inhibitor that
suppresses osteoclast differentiation and bone resorption.
AB - In search of anti-bone resorbing agents for the potential treatment of
osteoporosis, we synthesized a novel compound Tert-butyl 4-(3-[1H-indole-2
carboxamido]benzoyl)piperazine-1-carboxylate (OA10) and found that OA10 is
capable of inhibiting RANKL-mediated osteoclast formation and osteoclastic bone
resorption in a dose-dependent manner. This biological effect is further
supported by the fact that OA10 suppressed osteoclastic-specific gene expression,
including tartrate-resistant acid phosphatase, cathepsin K receptor, and
calcitonin receptor. Further molecular mechanism investigation revealed OA10
inhibited p38 phosphorylation, suppressed c-fos and NFATc1 expression without
affecting NF-kappaB or JNK signaling pathways. Taken together, this study
suggested that OA10 can inhibit osteoclastogenesis by suppressing p38-c-Fos
NFATc1 cascade. OA10 may be developed as a therapeutic drug for osteoclast
related osteolytic diseases.
PMID- 24357525
TI - Progress and controversies: radiation therapy for invasive breast cancer.
AB - Radiation therapy is a critical component of the multidisciplinary management of
invasive breast cancer. In appropriately selected patients, radiation not only
improves local control, sparing patients the morbidity and distress of local
recurrence, but it also improves survival by preventing seeding and reseeding of
distant metastases from persistent reservoirs of locoregional disease. In recent
years, considerable progress has been made toward improving our ability to select
patients most likely to benefit from radiotherapy and to administer treatment in
ways that maximize clinical benefit while minimizing toxicity and burden. This
article reviews the role of radiation therapy in invasive breast cancer
management, both after breast-conserving surgery and after mastectomy. It focuses
particularly on emerging evidence that helps to define the clinical situations in
which radiotherapy is indicated, the appropriate targets of treatment, and
optimal approaches for minimizing both the toxicity and the burden of treatment,
all in the context of the evolving surgical and systemic management of this
common disease. It includes a discussion of new approaches in breast cancer
radiotherapy, including hypofractionation and intensity modulation, as well as a
discussion of promising avenues for future research.
PMID- 24357526
TI - Virtual surgical planning improves surgical outcome measures in obstructive sleep
apnea surgery.
AB - OBJECTIVES/HYPOTHESIS: Determine the feasibility and accuracy of using virtual
surgical planning (VSP) to direct the surgical and polysomnography (PSG) outcomes
of patients with obstructive sleep apnea (OSA). STUDY DESIGN: Prospective case
series. METHODS: Skeletal and soft tissue dimensions were measured from computed
tomography (CT) to include posterior airway space (PAS) diameters at the occlusal
(PAS-O) and mandibular (PAS-M) plane, position of the maxilla, and tooth-to-lip
distance. All patients underwent an in-lab attended PSG whereby apnea-hypopnea
index (AHI), respiratory disturbance index (RDI), and lowest oxyhemoglobin
saturation percent (LSAT) were measured preoperatively and at least 9 months
postoperatively. RESULTS: Four patients with OSA demonstrated a mean AHI and RDI
of 60.1 and 69.5 events per hour, respectively. The mean preoperative LSAT was
76%. Mean CT-based measures for PAS-O and PAS-M were 3.08 mm and 9.03 mm,
respectively. VSP was used to direct the amount of advancement and impaction in
maxillomandibular advancement (MMA) surgery. The mean PAS-O and PAS-M
postoperative measures significantly increased to 8.15 and 14 mm (P < .004),
whereas the mean tooth-to-lip relationship stayed the same, 3.17 to 3.18, P =
.98. The AHI and RDI significantly improved to 2.83 and 4.5 events per hour,
respectively, P = .03, whereas the LSAT improved from 76% to 87%. CONCLUSIONS:
VSP for MMA in OSA patients is feasible and safe while offering improvements in
the predictability of airway change and tooth-to-lip measures.
PMID- 24357527
TI - An impairment of long distance SOX10 regulatory elements underlies isolated
Hirschsprung disease.
AB - A deletion encompassing several SOX10 enhancers was recently identified in a
patient presenting with Waardenburg syndrome type 4 (WS4), which is defined as a
combination of Hirschsprung disease (HSCR, intestinal aganglionosis) and WS
(deafness and pigmentation defects). The expression patterns of some of the known
SOX10 enhancers in animal models led to the speculation that endophenotypes of
WS4 may be linked to mutations within some of these sequences. The present study
investigated deletions and point mutations within four SOX10 enhancers in 144
unexplained isolated HSCR cases. One deletion and two point mutations affecting
binding sites for known neural crest transcription factors were identified. In
vitro functional analysis revealed that the first point mutation disrupts
autoregulation by SOX10, whereas the second affects AP2a and SOX10 synergistic
activity. The present findings suggest that the mutations within SOX10 enhancers
contribute to isolated HSCR.
PMID- 24357528
TI - Pediatric hospital discharge interventions to reduce subsequent utilization: a
systematic review.
AB - BACKGROUND: Reducing avoidable readmission and posthospitalization emergency
department (ED) utilization has become a focus of quality-of-care measures and
initiatives. For pediatric patients, no systematic efforts have assessed the
evidence for interventions to reduce these events. PURPOSE: We sought to
synthesize existing evidence on pediatric discharge practices and interventions
to reduce hospital readmission and posthospitalization ED utilization. DATA
SOURCES: PubMed and the Cumulative Index to Nursing and Allied Health Literature.
STUDY SELECTION: Studies available in English involving pediatric inpatient
discharge interventions with at least 1 outcome of interest were included. DATA
EXTRACTION: We utilized a modified Cochrane Good Practice data extraction tool
and assessed study quality with the Downs and Black tool. DATA SYNTHESIS: Our
search identified a total of 1296 studies, 14 of which met full inclusion
criteria. All included studies examined multifaceted discharge interventions
initiated in the inpatient setting. Overall, 2 studies demonstrated statistically
significant reductions in both readmissions and subsequent ED visits, 4 studies
demonstrated statistically significant reductions in either readmissions or ED
visits, and 2 studies found statistically significant increases in subsequent
utilization. Several studies were not sufficiently powered to detect changes in
either subsequent utilization outcome measure. CONCLUSIONS: Interventions that
demonstrated reductions in subsequent utilization targeted children with specific
chronic conditions, providing enhanced inpatient feedback and education
reinforced with postdischarge support. Interventions seeking to reduce subsequent
utilization should identify an individual or team to assume responsibility for
the inpatient-to-outpatient transition and offer ongoing support to the family
via telephone or home visitation following discharge.
PMID- 24357529
TI - A patient with Simpson-Golabi-Behmel syndrome, biliary cirrhosis and successful
liver transplantation.
AB - Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked
inherited overgrowth syndrome caused by a loss of function mutation in the GPC3
gene. Affected patients present a variable phenotype with pre- and post-natal
macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital
anomalies. Intellectual disability is not constant. About 10% of patients have an
increased risk of developing embryonic tumors in early childhood. Only one case
of biliary disease has been described so far. GPC3 is localized on Xq26. It
encodes for glypican 3, a heparan sulfate proteoglycan, which among its different
known roles, negatively regulates liver regeneration and hepatocyte
proliferation. This report concerns a male with a SGBS1, carrier of a GPC3
pathogenic mutation, and neonatal liver disease, who developed an early biliary
cirrhosis. Together with the associated risk of cancer and developmental delay,
liver transplantation was discussed and then successfully performed at the age of
19 months. A hypothesis on the role of GPC3 in the patient's liver disease is
also proposed.
PMID- 24357530
TI - Demographic consequences of climate change and land cover help explain a history
of extirpations and range contraction in a declining snake species.
AB - Developing conservation strategies for threatened species increasingly requires
understanding vulnerabilities to climate change, in terms of both demographic
sensitivities to climatic and other environmental factors, and exposure to
variability in those factors over time and space. We conducted a range-wide,
spatially explicit climate change vulnerability assessment for Eastern Massasauga
(Sistrurus catenatus), a declining endemic species in a region showing strong
environmental change. Using active season and winter adult survival estimates
derived from 17 data sets throughout the species' range, we identified
demographic sensitivities to winter drought, maximum precipitation during the
summer, and the proportion of the surrounding landscape dominated by agricultural
and urban land cover. Each of these factors was negatively associated with active
season adult survival rates in binomial generalized linear models. We then used
these relationships to back-cast adult survival with dynamic climate variables
from 1950 to 2008 using spatially explicit demographic models. Demographic models
for 189 population locations predicted known extant and extirpated populations
well (AUC = 0.75), and models based on climate and land cover variables were
superior to models incorporating either of those effects independently. These
results suggest that increasing frequencies and severities of extreme events,
including drought and flooding, have been important drivers of the long-term
spatiotemporal variation in a demographic rate. We provide evidence that this
variation reflects nonadaptive sensitivity to climatic stressors, which are
contributing to long-term demographic decline and range contraction for a species
of high-conservation concern. Range-wide demographic modeling facilitated an
understanding of spatial shifts in climatic suitability and exposure, allowing
the identification of important climate refugia for a dispersal-limited species.
Climate change vulnerability assessment provides a framework for linking
demographic and distributional dynamics to environmental change, and can thereby
provide unique information for conservation planning and management.
PMID- 24357531
TI - Lin28a--boost your energy for youthful regeneration.
AB - The regenerative capacity of most tissues declines dramatically after embryonic
development and during post-natal life. The underlying mechanisms of this
phenomenon are incompletely understood. In a recent issue of Cell, Shyh-Chang and
colleagues provide experimental evidence that Lin28 prolongs youthful
regenerative capacity by increasing oxidative glucose metabolism (Shyh-Chang et
al, 2013).
PMID- 24357532
TI - KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic
hypoglycemia.
AB - Patients with loss-of-function mutations in KCNQ1 have KCNQ1 long QT syndrome
(LQTS). KCNQ1 encodes a voltage-gated K(+) channel located in both cardiomyocytes
and pancreatic beta-cells. Inhibition of KCNQ1 in beta-cells increases insulin
secretion. Therefore KCNQ1 LQTS patients may exhibit increased insulin secretion.
Fourteen patients, from six families, diagnosed with KCNQ1 LQTS were individually
matched to two randomly chosen BMI-, age-, and sex-matched control participants
and underwent an oral glucose tolerance test (OGTT), a hypoglycemia
questionnaire, and continuous glucose monitoring. KCNQ1 mutation carriers showed
increased insulin release (area under the curve 45.6 +/- 6.3 vs. 26.0 +/- 2.8 min
? nmol/L insulin) and beta-cell glucose sensitivity and had lower levels of
plasma glucose and serum potassium upon oral glucose stimulation and increased
hypoglycemic symptoms. Prolonged OGTT in four available patients and matched
control subjects revealed hypoglycemia in carriers after 210 min (range 1.4-3.6
vs. 4.1-5.3 mmol/L glucose), and 24-h glucose profiles showed that the patients
spent 77 +/- 18 min per 24 h in hypoglycemic states (<3.9 mmol/L glucose) with 36
+/- 10 min (<2.8 mmol/L glucose) vs. 0 min (<3.9 mmol/L glucose) for the control
participants. The phenotype of patients with KCNQ1 LQTS, caused by mutations in
KCNQ1, includes, besides long QT, hyperinsulinemia, clinically relevant
symptomatic reactive hypoglycemia, and low potassium after an oral glucose
challenge, suggesting that KCNQ1 mutations may explain some cases of "essential"
reactive hypoglycemia.
PMID- 24357533
TI - "Lazy" nigrostriatal synapses in the heterozygous PINK1 mouse model of familial
Parkinson's disease.
PMID- 24357534
TI - Assessment of buccal aerosolized midazolam for pediatric conscious sedation.
AB - AIM: To assess the acceptance and efficacy of aerosolized midazolam through
buccal mucosa for conscious sedation. METHODS: Thirty-five children aged 2-6
years with Grade I and II Frankl behavior rating scale were selected for various
dental procedures under local anesthesia. Initially behavior-shaping procedures
were used and Houpt behavior scoring was recorded. Thereafter, midazolam was
administered using a spray through buccal mucosa and scores for acceptance of
drug and behavior after sedation were recorded. The data were compiled and a
Wilcoxon signed ranks test was used to assess the difference in behavior before
and after the sedation. RESULTS: Eighty-three percent of the patients accepted
the drug without any complaint. A statistically significant improvement was seen
in the Houpt scores before and after drug administration (P < 0.001).
CONCLUSIONS: Buccal aerosolized midazolam can be used successfully for pediatric
conscious sedation.
PMID- 24357535
TI - Solvent-free and catalysts-free chemistry: a benign pathway to sustainability.
AB - In the past decade, alternative benign organic methodologies have become an
imperative part of organic syntheses and chemical reactions. The various new and
innovative sustainable organic reactions and methodologies using no solvents or
catalysts and employing alternative energy inputs such as microwaves, sonication,
conventional and room temperature heating conditions, mechanochemical mixing, and
high-speed ball milling are discussed in detail. Environmentally benign and
pharmaceutically important reactions such as multicomponent, condensation, and
Michael addition reactions; ring opening of epoxides; and oxidation and other
significant organic reactions are discussed. An overview of benign reactions
through solvent- and catalyst-free (SF-CF) chemistry and a critical perspective
on emerging synergies between SF-CF organic reactions are discussed.
PMID- 24357536
TI - Unsaturated aldehydes induce CCK secretion via TRPA1 in STC-1 cells.
AB - SCOPE: Cholecystokinin (CCK) producing cells sense luminal contents to regulate
the exocrine pancreas, gastric motility, and appetite. Although long-chain fatty
acids (FAs, >= C12) are well known to stimulate CCK secretion, the CCK-releasing
activities of other aliphatic compounds, such as aldehydes (Alds) or alcohols
(Alcs), have not been studied. METHODS AND RESULTS: We tested the CCK-releasing
activities of various aliphatic compounds with various carbon chain lengths (C3
C13) and degrees of unsaturation in the enteroendocrine cell line STC-1. CCK
released from the cell was measured using an ELISA, and intracellular calcium
concentration was measured using Fura-2. Mono- and di-unsaturated Alds at 100
MUM, but not saturated Alds, induced CCK secretion in STC-1 cells. Alcs and FAs
failed to induce CCK secretion, regardless of carbon chain length or degree of
unsaturation. Unsaturated Alds increased intracellular calcium concentration, but
saturated Alds, Alcs, and FAs did not. Intracellular calcium mobilization and CCK
secretion induced by unsaturated Alds was abolished in the absence of
extracellular calcium. In addition, the inhibition of the transient receptor
potential ankyrin 1 (TRPA1) channel suppressed unsaturated Ald-induced CCK
secretion and intracellular calcium mobilization. CONCLUSION: Unsaturated Alds
are potent aliphatic stimulants for CCK secretion through the activation of
TRPA1.
PMID- 24357537
TI - Standardizing analysis of circulating microRNA: clinical and biological
relevance.
AB - Circulating microRNAs (c-miRNAs) provide a new dimension as clinical biomarkers
for disease diagnosis, progression, and response to treatment. However, the
discovery of individual miRNAs from biofluids that reliably reflect disease
states is in its infancy. The highly variable nature of published studies
exemplifies a need to standardize the analysis of miRNA in circulation. Here, we
show that differential sample handling of serum leads to inconsistent and
incomparable results. We present a standardized method of RNA isolation from
serum that eliminates multiple freeze/thaw cycles, provides at least three
normalization mechanisms, and can be utilized in studies that compare both
archived and prospectively collected samples. It is anticipated that serum
processed as described here can be profiled, either globally or on a gene by gene
basis, for c-miRNAs and other non-coding RNA in the circulation to reveal novel,
clinically relevant epigenetic signatures for a wide range of diseases.
PMID- 24357538
TI - The role of inner strength in quality of life and self-management in women
survivors of cancer.
AB - The role of inner strength in quality of life (QOL) and self-management, primary
variables in the Theory of Inner Strength, were examined with demographic and
clinical characteristics in 107 women with cancer. The strongest predictors of
QOL were depressive symptoms, inner strength, and time since diagnosis,
respectively, accounting for 82% of the variance in QOL. When depressive symptoms
were excluded due to multicollinearity, 64% of variance in QOL was explained by
inner strength, time since diagnosis, and comorbidities, with inner strength the
strongest predictor. The strongest predictors of self-management were depressive
symptoms and inner strength, accounting for 17% of the variance. Results
contribute to theory development and suggest the value of supporting inner
strength to enhance QOL in cancer survivors.
PMID- 24357539
TI - Interstitial deletion at chromosome 16p13.2 involving TMEM114 (transmembrane
protein 114) in a boy and his father without cataract.
PMID- 24357540
TI - Prevalence of cancer in Parkinson's disease related to R1441G and G2019S
mutations in LRRK2.
AB - An inverse relationship between Parkinson's disease (PD) and cancer has been
described. However, the association between cancers and genetic forms of PD, in
particular the R1441G mutation in the LRRK2 gene, is not well known. The
objective of this work was to analyze cancer prevalence in PD patients with
R1441G or G2019S mutations in LRRK2, and in idiopathic PD (iPD). A total of 732
patients with PD (70 and 25 carriers of R1441G or G2019S mutations,
respectively), and 177 controls, were linked using a population-based cancer
registry of the Spanish province of Gipuzkoa. Cancer prevalence was not
significantly higher in PD-G2019S carriers (20%) than in PD-R1441G carriers
(14.3%), iPD (13.8%), or controls (12.5%). With the exception of a high
prevalence of hematological cancers (crude odds ratio of 7.1) in the R1441G
group, specific cancer types were not increased in PD mutation carriers. In both
the carrier and iPD groups, cancers were diagnosed after the onset of PD. PD
patients had a similar prevalence of cancer to control subjects. There was no
increased association between G2019S or R1441G mutations and any type of cancer.
Although there was a higher prevalence of hematological cancers in the R1441G
group, the low number of such cancers overall makes this finding of uncertain
significance. There was a slightly higher but not statistically significant
prevalence of non-skin cancers in the G2019S group, suggesting that further study
to evaluate the association should be undertaken prior to ascribing an increased
cancer risk to this population.
PMID- 24357541
TI - Underuse of the health care system by persons with diabetes mellitus and diabetic
macular edema in the United States.
AB - IMPORTANCE: Thickening of the center of the retina, diabetic macular edema (DME),
is the most common cause of visual loss due to diabetes mellitus. Treatment of
DME has improved dramatically, and the prompt diagnosis of DME and referral of
these patients have become more critical. Nonetheless, awareness of and care for
DME in the US population is uncharacterized. OBJECTIVE: To characterize eye care
and awareness of eye disease among persons with DME in the general US population.
DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of data from
participants in the 2005 to 2008 National Health and Nutrition Examination Survey
40 years or older with diabetes mellitus and fundus photographs. MAIN OUTCOMES
AND MEASURES: Among persons with DME, (1) awareness that diabetes has affected
their eyes; (2) report on the last time they visited a diabetes specialist; (3)
report on their last eye examination with pupil dilation; and (4) prevalence of
visual impairment. RESULTS: In 2010, only 44.7% (95% CI, 27.0%-62.4%) of US
adults 40 years or older with DME reported being told by a physician that
diabetes had affected their eyes or that they had retinopathy; 46.7% (95% CI,
27.5%-66.0%), that they had visited a diabetes nurse educator, dietician, or
nutritionist for their diabetes mellitus more than 1 year ago or never; and 59.7%
(95% CI, 43.5%-75.9%), that they had received an eye examination with pupil
dilation in the last year. Among persons with DME, 28.7% (95% CI, 12.7%-44.7%)
were visually impaired (defined as visual acuity worse than 20/40 in the eye with
DME) based on visual acuity at the initial examination and 16.0% (95% CI, 2.5%
29.4%) based on best-corrected visual acuity. CONCLUSIONS AND RELEVANCE: Many
persons with diabetes mellitus in the United States are not getting care that can
prevent visual impairment and blindness. Strategies to increase awareness are
warranted, especially given the recent availability of improved therapies for
DME.
PMID- 24357542
TI - Polyols and polyurethanes from the liquefaction of lignocellulosic biomass.
AB - Polyurethanes (PUs), produced from the condensation polymerizations between
polyols and isocyanates, are one of the most versatile polymer families.
Currently, both polyols and isocyanates are largely petroleum derived. Recently,
there have been extensive research interests in developing bio-based polyols and
PUs from renewable resources. As the world's most abundant renewable biomass,
lignocellulosic biomass is rich in hydroxyl groups and has potential as a
feedstock to produce bio-based polyols and PUs. Lignocellulosic biomass can be
converted to liquid polyols for PU applications through acid- or base-catalyzed
atmospheric liquefaction processes using polyhydric alcohols as liquefaction
solvents. Biomass liquefaction-derived polyols can be used to prepare various PU
products, such as foams, films and adhesives. The properties of biomass
liquefaction-derived polyols and PUs depend on various factors, such as feedstock
characteristics, liquefaction conditions, and PU formulations.
PMID- 24357544
TI - Molecular and chemical investigations and comparisons of biomaterials for ocular
surface regeneration.
AB - This study investigated and compared the ultrastructural and chemical properties
of representative biomaterials for ocular surface regeneration: a human amniotic
membrane (AM) in a basal plate, a human AM in reflected chorion, a preserved AM,
and a human corneo-scleral tissue. Assessments of the morphological differences
in the extracellular matrices were evaluated by hematoxylin-eosin, Masson's
trichrome (for total collagen), and picrosirius-red (for newly synthesized
collagen) staining. Assessments of the changes in the molecular structures and
chemical compositions of the biomaterials for ocular surface regeneration were
evaluated by Raman spectroscopy. A placental AM (52 %) was a dense and thick
collagenous structure compared to a reflected AM (23 %). The spectroscopy did not
obtain any structural information for a preserved AM. The cornea group (100 %,
control) and sclera group (104 %) showed the collagen lamellae and interfibrillar
spacing, and a slight inflammatory reaction with more fibrous and granulomatous
tissues. There was a formation of newly synthesized collagen in a placental AM,
while there were few collagen components in a reflected AM. Human AM tissues
showed consistent Raman spectra and the characteristic collagen bands, similar to
the corneal and scleral tissues. Therefore, these findings suggest that human
placental AM and reflected AM are structurally suitable for scleral and corneal
surface regeneration, respectively, while human placental or preserved AM and
reflected AM are molecularly and chemically suitable for corneal and scleral
surface regeneration, respectively.
PMID- 24357543
TI - The resolution of neuroinflammation in neurodegeneration: leukocyte recruitment
via the choroid plexus.
AB - Inflammation is an integral part of the body's physiological repair mechanism,
unless it remains unresolved and becomes pathological, as evident in the
progressive nature of neurodegeneration. Based on studies from outside the
central nervous system (CNS), it is now understood that the resolution of
inflammation is an active process, which is dependent on well-orchestrated innate
and adaptive immune responses. Due to the immunologically privileged status of
the CNS, such resolution mechanism has been mostly ignored. Here, we discuss
resolution of neuroinflammation as a process that depends on a network of immune
cells operating in a tightly regulated sequence, involving the brain's choroid
plexus (CP), a unique neuro-immunological interface, positioned to integrate
signals it receives from the CNS parenchyma with signals coming from circulating
immune cells, and to function as an on-alert gate for selective recruitment of
inflammation-resolving leukocytes to the inflamed CNS parenchyma. Finally, we
propose that functional dysregulation of the CP reflects a common underlying
mechanism in the pathophysiology of neurodegenerative diseases, and can thus
serve as a potential novel target for therapy.
PMID- 24357545
TI - Cytokine profile in the gingival crevicular fluid of rheumatoid arthritis
patients with chronic periodontitis.
AB - The aim was to assess the cytokine profile in the gingival crevicular fluid (GCF)
of rheumatoid arthritis (RA) patients with chronic periodontitis (CP). Databases
were searched from 1991 to August 2013 using a combination of various keywords.
Eight studies were included. The GCF concentrations of interleukin (IL)-1beta, IL
4, IL-10, matrix metalloproteinase (MMP)-8, MMP-13 and tumor necrosis factor
alpha (TNF-alpha) were reported to be higher in patients with RA than in healthy
controls (HC) without CP. In one study, TNF-alpha levels in GCF were
significantly higher in HC than in RA patients receiving anti-TNF-alpha therapy.
One study reported no significant difference in GCF TNF-alpha levels among RA
patients and HC regardless of anti-TNF-alpha therapy. One study reported no
difference in IL-1beta and prostaglandin E2 levels among RA patients and HC with
CP. Raised levels of proinflammatory cytokines are exhibited in the GCF of RA
patients with CP.
PMID- 24357547
TI - Special section guest editorial: Optical elastography and measurement of tissue
biomechanics.
PMID- 24357546
TI - Heparan sulfate proteoglycans and human breast cancer epithelial cell
tumorigenicity.
AB - Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular
matrix that mediate cell proliferation, invasion, and cellular signaling. The
biological functions of HSPGs are linked to their co-stimulatory effects on
extracellular ligands (e.g., WNTs) and the resulting activation of transcription
factors that control mammalian development but also associated with
tumorigenesis. We examined the expression profile of HSPG core protein syndecans
(SDC1-4) and glypicans (GPC1-6) along with the enzymes that initiate or modify
their glycosaminoglycan chains in human breast cancer (HBC) epithelial cells.
Gene expression in relation to cell proliferation was examined in the HBC cell
lines MCF-7 and MDA-MB-231 following treatment with the HS agonist heparin.
Heparin increased gene expression of chain initiation and modification enzymes
including EXT1 and NDST1, as well as core proteins SDC2 and GPC6. With HS/Wnt
interactions established, we next investigated WNT pathway components and
observed that increased proliferation of the more invasive MDA-MB-231 cells is
associated with activation of the Wnt signaling pathway. Specifically, there was
substantial upregulation (>5-fold) of AXIN1, WNT4A, and MYC in MDA-MB-231 but not
in MCF-7 cells. The changes in gene expression observed for HSPG core proteins
and related enzymes along with the associated Wnt signaling components suggest
coordinated interactions. The influence of HSPGs on cellular proliferation and
invasive potential of breast cancer epithelial cells are cell and niche specific.
Further studies on the interactions between HSPGs and WNT ligands may yield
clinically relevant molecular targets, as well as new biomarkers for
characterization of breast cancer progression.
PMID- 24357548
TI - Viscosity measurement based on shear-wave laser speckle contrast analysis.
AB - Tissue viscosity is correlated with tissue pathological changes and provides
information for tissue characterization. In this study, we report an optical
method to track continuous shear-wave propagation at centimeter depths in an
optically turbid medium. Shear-wave attenuation coefficients were measured at
multiple frequencies using shear-wave laser speckle contrast analysis (SW-LASCA)
to quantitatively estimate tissue viscosity using the Voigt model. Shear waves
were generated within tissue-mimicking phantoms by an amplitude-modulated
ultrasound (modulation frequency: 100 to 600 Hz) and tracked by time-resolved
laser speckle contrast difference received on a charged-coupled device camera.
Averaged contrast difference over a selected time window was related to shear
wave amplitude and used to calculate the shear-wave attenuation coefficient.
Phantoms of varying viscosities (0.1 and 0.3 Pa s) were studied. Attenuation
coefficients for different shear-wave frequencies (100 to 600 Hz) were
calculated. Derived viscosity values had a maximum standard deviation of 9%, and
these values were consistent with the independent measurements reported in a
previous study using nonoptical methods.
PMID- 24357549
TI - From supersonic shear wave imaging to full-field optical coherence shear wave
elastography.
AB - Elasticity maps of tissue have proved to be particularly useful in providing
complementary contrast to ultrasonic imaging, e.g., for cancer diagnosis at the
millimeter scale. Optical coherence tomography (OCT) offers an endogenous
contrast based on singly backscattered optical waves. Adding complementary
contrast to OCT images by recording elasticity maps could also be valuable in
improving OCT-based diagnosis at the microscopic scale. Static elastography has
been successfully coupled with full-field OCT (FF-OCT) in order to realize both
micrometer-scale sectioning and elasticity maps. Nevertheless, static
elastography presents a number of drawbacks, mainly when stiffness quantification
is required. Here, we describe the combination of two methods: transient
elastography, based on speed measurements of shear waves induced by ultrasonic
radiation forces, and FF-OCT, an en face OCT approach using an incoherent light
source. The use of an ultrafast ultrasonic scanner and an ultrafast camera
working at 10,000 to 30,000 images/s made it possible to follow shear wave
propagation with both modalities. As expected, FF-OCT is found to be much more
sensitive than ultrafast ultrasound to tiny shear vibrations (a few nanometers
and micrometers, respectively). Stiffness assessed in gel phantoms and an ex vivo
rat brain by FF-OCT is found to be in good agreement with ultrasound shear wave
elastography.
PMID- 24357550
TI - Commentary.
PMID- 24357551
TI - Growth curves in Down syndrome: implications for clinical practice.
AB - Growth curves have been developed for individuals with Down syndrome (DS) in
several countries. However, in order to facilitate the preparation of clinical
guidelines it is necessary to verify the eligibility of these curves. The search
was conducted according to the PRISMA method (Preferred Reporting Items for
Systematic reviews and Meta-Analyses). It was conducted between July 2012 and
June 2013 in MEDLINE/PubMed and BIREME. The inclusion and exclusion criteria were
applied to identify the studies and a total of 16 relevant articles were
selected. The aspects analyzed in the articles consisted of sample size, number
of observations, age group, anthropometric variables, standard deviation scores
(SDS), type of study, collection and analysis of data, participants,
inclusion/exclusion criteria and outcomes. The mean, standard deviations (SDs)
and percentiles for sex and age were used to develop the curve of weight, height,
and head circumference. The individuals with DS presented growth between -0.4 and
-4.0 SDS in comparison to healthy controls. The variation in these observations
can be explained by genetic differences, secular trends in growth and disease
status. Regarding the limitations identified, it was observed that most of the
studies did not provide data concerning the number of individuals and
observations, mean values and respective SDs by sex and age. In addition, most
studies did not use LMS methods to evaluate asymmetry, the median and data
variability. In conclusion, the results of this review demonstrated that in order
to avoid false diagnoses in children and adolescents with DS new growth curves
must be developed.
PMID- 24357552
TI - Assessing the predictive performance of risk-based water quality criteria using
decision error estimates from receiver operating characteristics (ROC) analysis.
PMID- 24357553
TI - The adipokine profile of metabolically benign obese and at-risk normal weight
postmenopausal women: the Women's Health Initiative Observational Study.
AB - OBJECTIVE: Nearly, a third of obese individuals, termed metabolically benign
obese, have a low burden of adiposity-related cardiometabolic abnormalities,
whereas a substantial proportion of normal-weight individuals possess risk
factors. METHODS: In cross-sectional analyses of 699 normal weight and 1,294
overweight/obese postmenopausal women enrolled in a nested case-control stroke
study ancillary to the Women's Health Initiative Observational Study, we compared
levels of adiponectin, leptin, and resistin among metabolically benign normal
weight, at-risk normal weight, metabolically benign obese, and at-risk obese
women using components of the ATP III definition of the metabolic syndrome
(metabolically benign: <=1 of the four components; at-risk phenotype: >=2
components or diabetes). RESULTS: Overall, 382/699 normal-weight women (54.6%)
and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among
normal-weight women, at-risk women had higher leptin and lower adiponectin levels
compared to metabolically benign women; multivariate-adjusted odds ratios were
significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46;
1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81
3.84). Compared to metabolically benign overweight/obese women, at-risk obese
women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and
adiponectin in the bottom tertile (2.78; 2.04-3.77). CONCLUSIONS: Overall,
metabolically benign overweight/obese women had an intermediate adipokine profile
(between at-risk obese and metabolically benign normal-weight women), whereas at
risk normal-weight women had a less favorable profile compared to metabolically
benign normal-weight women. As adiponectin was the only adipokine independent of
BMI, it may be most likely to have a role in the etiological pathway of these
phenotypes.
PMID- 24357554
TI - Biodegradable, pH-responsive carboxymethyl cellulose/poly(acrylic acid) hydrogels
for oral insulin delivery.
AB - Biodegradable and pH-responsive carboxymethyl cellulose/poly(acrylic acid) hybrid
hydrogels are synthesized. The hydrogels deswell in acidic artificial gastric
fluid (AGF) but rapidly swell in neutral artificial intestinal fluid (AIF),
rendering selective enzymatic degradation of the gels as well as accelerated drug
release from insulin-loaded hydrogels in AIF. Oral administration of insulin
loaded hydrogels to streptozotocin-induced diabetic rats leads to a continuous
decline in the fasting blood glucose level within 6 h post-administration, and
the relative pharmacological availability increases more than 10 times compared
to oral administration of free insulin solution. The relative bioavailability of
hydrogel-encapsulated insulin after oral administration to healthy rabbits is
6.6%.
PMID- 24357555
TI - Permanent maxillary canines - review of eruption pattern and local etiological
factors leading to impaction.
AB - The position of the permanent maxillary canine at the angle of the mouth is
strategically significant in maintaining the harmony and symmetry of the occlusal
relationship. However, the maxillary canine is the second most frequently
impacted tooth, with prevalence reported to be between 1% and 2%. Moreover,
treatment of this condition is often complex and involves substantial time and
financial cost. Hence, it is only prudent to monitor the eruption and identify
the etiological factors that lead to impaction of the maxillary canine. Numerous
researchers have tried to identify specific and nonspecific etiological factors
responsible for displacement of canines. The purpose of this review was to track
the development processes of maxillary canines and determine the hindrances that
affect the eruption at different ages. Awareness of the eruption process and
etiology of noneruption will help to reduce the incidence of impacted canines by
allowing for early recognition and interceptive treatment.
PMID- 24357556
TI - Field type, trap type and field-edge characteristics affect Rhagoletis mendax
captures in lowbush blueberries.
AB - BACKGROUND: Blueberry maggot, Rhagoletis mendax Curran (Diptera: Tephritidae), is
the most important pest of blueberries in eastern North America. Insecticide use
in fruit-bearing lowbush blueberry fields could be reduced with management
strategies focused on vegetative fields. Fly distribution and fruit infestation
levels were assessed where fruit-bearing and vegetative fields adjoin and along
forested edges of vegetative fields. RESULTS: Along adjoining edges, immature
female flies were captured in fruiting fields and mature females in vegetative
fields throughout the season. Male fly captures and fruit infestation levels were
greater at 5 m than at 30 m from the edge. Along forested edges, fly captures
were best predicted by densities of ripe lowbush blueberries and large coniferous
trees. Maggot infestation level in lowbush blueberries was best predicted by
blueberry density and small deciduous trees. Bunchberry, Cornus canadensis L.,
was the only non-crop host in which blueberry maggot was found. CONCLUSIONS: We
have shown that relatively high numbers of flies occur in vegetative fields and
at edges of fruiting fields. Ripe blueberries and certain vegetation in forested
edges affect fly distribution and probably maintain populations. These results
may help to predict where controls for blueberry maggot should be targeted and
suggest that management strategies focused on vegetative fields and field edges
may be worthwhile.
PMID- 24357558
TI - Telling them to brush and floss is just not working.
PMID- 24357559
TI - Oral cancer screenings.
PMID- 24357557
TI - Mec1/ATR regulates the generation of single-stranded DNA that attenuates Tel1/ATM
signaling at DNA ends.
AB - Tel1/ATM and Mec1/ATR checkpoint kinases are activated by DNA double-strand
breaks (DSBs). Mec1/ATR recruitment to DSBs requires the formation of RPA-coated
single-stranded DNA (ssDNA), which arises from 5'-3' nucleolytic degradation
(resection) of DNA ends. Here, we show that Saccharomyces cerevisiae Mec1
regulates resection of the DSB ends. The lack of Mec1 accelerates resection and
reduces the loading to DSBs of the checkpoint protein Rad9, which is known to
inhibit ssDNA generation. Extensive resection is instead inhibited by the Mec1-ad
mutant variant that increases the recruitment near the DSB of Rad9, which in turn
blocks DSB resection by both Rad53-dependent and Rad53-independent mechanisms.
The mec1-ad resection defect leads to prolonged persistence at DSBs of the MRX
complex that causes unscheduled Tel1 activation, which in turn impairs checkpoint
switch off. Thus, Mec1 regulates the generation of ssDNA at DSBs, and this
control is important to coordinate Mec1 and Tel1 signaling activities at these
breaks.
PMID- 24357560
TI - Improving oral health literacy - the new standard in dental hygiene practice.
AB - PURPOSE: Oral diseases continue to burden a significant portion of the American
public, especially those in low-income groups. The misconception that oral health
is less important than general health exists among America's citizens even though
it has been 13 years since the Surgeon General's report affirmed oral health as
an essential component of general health. Research has shown that poor oral
health literacy (OHL) affects oral health, can negatively influence quality of
life and has a significant financial impact on society. National initiatives to
increase the OHL levels of American citizens include training health care
professionals about effective communication skills and disseminating oral health
information to groups outside of dentistry. This paper describes a new course on
OHL and communication techniques for dental hygiene students at the University of
Maryland, School of Dentistry.
PMID- 24357561
TI - Improving oral health outcomes from pregnancy through infancy.
AB - PURPOSE: The purpose of this paper is to provide an overview of current
professional guidelines regarding oral health care through pregnancy and infancy
stages, and to include risks associated with treatment, as well as health care
providers' beliefs and attitudes surrounding treatment of these specific
populations. Although dental treatment during the second trimester is ideal,
there is no indication that preventive or restorative dental treatment during any
trimester of pregnancy can cause harm to the mother or developing fetus. Despite
these recommendations, routine dental care is often voluntarily avoided or
postponed for the duration of pregnancy. Post-delivery, preventive oral care is
typically postponed for a child until 3 years of age, years after the first tooth
has erupted. While most health care professionals agree on the importance of good
oral health in every stage of life, it is not being addressed. Whether it is
based on misconceptions or lack of knowledge, health care providers are
performing inadequate oral care for these patients. Recommendations to increase
health care during pregnancy and infancy should include improved advocacy of the
established oral health care guidelines within each professional organization. In
addition, curriculum revision should occur at the university level, to ensure
future health care professionals will have a strong oral health foundation.
Lastly, a collaborative effort needs to occur between all health care providers
to better treat the patient's overall health, not only the specifics of one
professional discipline. As health care professionals we are all responsible for
the complete well-being of our patients, and an interdisciplinary approach will
better ensure we accomplish this task.
PMID- 24357562
TI - The relationship between postmenopausal osteoporosis and periodontal disease.
AB - PURPOSE: The purpose of this literature review is to summarize the scientific
evidence, examining the relationship between postmenopausal osteoporosis and
periodontal disease, and to determine if the relationship is causal or casual. A
total of 8 electronic databases were searched to identify studies that included
the following keywords: osteoporosis, periodontal disease, alveolar bone loss,
estrogen deficiency, tooth loss and postmenopausal. Relevant abstracts were
retrieved and critically evaluated. Based on the inclusion criteria of dentate
postmenopausal women, selected articles were identified to read for more thorough
examination. Of the 5 longitudinal studies reviewed, 4 (80%) showed an
association between osteoporosis and periodontal disease. A relationship between
the 2 diseases was demonstrated in 20 (80%) of the 25 cross-sectional studies.
All 3 of the case-control studies showed an association. These data suggest a
positive association between osteoporosis and periodontal disease. Determining
whether this relationship is causal will require more longitudinal studies. Based
on these findings, it is recommended that medical and dental professionals
enhance their collaborative actions for prevention, evaluation and treatment of
oral diseases and osteoporosis, in order to improve the health of these
postmenopausal women.
PMID- 24357563
TI - Teledentistry: a systematic review of clinical outcomes, utilization and costs.
AB - PURPOSE: The purpose of this systematic review is to identify clinical outcomes,
health care utilization and costs associated with teledentistry. Relevant
databases were searched for articles on teledentistry published until March 2012,
reference lists examined and key journals hand searched. Of a possible 58
articles, 19 studies met the inclusion criteria. Clinical outcomes were generally
improved following a teledentistry intervention and satisfaction with
teledentistry was consistently high. The few studies examining health care
utilization reported mixed findings, but preliminary evidence suggests cost
savings for health care facilities. There is a consistent trend in the literature
supporting the efficacy and effectiveness of teledentistry. Further research is
needed to identify the effectiveness, efficiency, utilization and costs of
teledentistry as it could provide the key to improving access to care.
PMID- 24357564
TI - Dental hygienists' knowledge, attitudes and practice behaviors regarding caries
risk assessment and management.
AB - PURPOSE: Lifelong control of disease processes associated with dental caries
should be an essential part of the process of care for practicing dental
hygienists. The purpose of this study was to identify the knowledge, attitudes
and practice behaviors among dental hygienists regarding caries risk assessment
(CRA) and management. METHODS: Utilizing the American Dental Hygienists'
Association (ADHA) Survey/Research Center database of all registered dental
hygienists in the U.S., 2,500 actively licensed dental hygienists were randomly
selected and sent a web-based survey via SurveyMonkeyTM. The survey included
items about practice characteristics and questions regarding knowledge, attitudes
and practice behaviors regarding CRA and management. Second and third emails were
sent to non-respondents. A 4-point Likert type scale (1=never, 2=sometimes,
3=frequently and 4=always) was used to rate the occurrence of caries management
recommendations used in the practice setting. Frequencies and percentiles were
used to evaluate demographic, knowledge and attitude information. RESULTS: The
response rate was 9% (n=219) - 87% were ADHA members. Participants reported a
high level of comfort (89%) in performing CRA, yet only 23% used an established
CRA/management instrument. Over-the-counter fluoride dentifrices (70.1%),
individualized oral hygiene instructions (86%) and individualized recare
intervals (73.7%) were most often used as caries management recommendations,
while low-dose fluoride rinses (45%) and prescription strength sodium fluoride
gel or paste (42%) were used less frequently. Dental hygienists scored high on
knowledge of CRA with the exception of white spot lesions as a risk factor (42%)
and efficacy of chlorhexidine in caries management (61%). CONCLUSION: There is a
need to improve practicing dental hygienists' knowledge and involvement in the
active management of caries. Focused training in the use of established
CRA/management tools should be designed to improve their knowledge and influence
practice behaviors.
PMID- 24357565
TI - Knowledge, attitude and practice regarding oral health among the rural government
primary school teachers of Mangalore, India.
AB - PURPOSE: This study was conducted to assess the knowledge, attitude and practice
regarding oral health among the Rural Government Primary school teachers of
Mangalore, Karnataka, India. METHODS: A self-administered close ended
questionnaire consisting of 16 items was distributed among the rural primary
school teachers of Mangalore (n=165). Comparison of knowledge and attitude
amongst the 3 age groups was done with Kruskal Wallis test. Comparison of mean
scores between the genders was done using Mann-Whitney-U test. Comparison of mean
scores across four educational qualification groups was done using Kruskal Wallis
test. RESULTS: Out of 165 primary school teachers to whom the questionnaires were
sent, 153 responded, yielding a 92.7% response rate. Results showed that
significant difference (p<0.01) was seen across the 3 age groups for the mean
practice scores. There was significant difference between the genders with
females scoring better for the mean knowledge, practice and the total scores.
Educational qualification did not make any significant difference in the
knowledge and practice on oral health. CONCLUSION: The study concluded that oral
health knowledge was lacking among the primary school teachers of rural
Mangalore, although practices were satisfactory. Oral health education program
targeting only the teachers is of utmost importance in the light of the present
study results.
PMID- 24357566
TI - Dental fluorosis and lumbar spine bone mineral density in adults, ages 20 to 49
years: results from the 2003 to 2004 National Health and Nutrition Examination
Survey.
AB - PURPOSE: Osteoporosis is an urgent public health concern. Many factors influence
bone mineral density (BMD), a criterion used to diagnose osteoporosis. The
purpose of this study was to determine if dental fluorosis may be a marker for
osteoporosis. The association between dental fluorosis and BMD at the lumbar
spine was examined. METHODS: Using a cross-sectional design with 1,805 adults,
ages 20 to 49 years, from the 2003 to 2004 National Health and Nutrition
Examination Survey, an analysis of the association between dental fluorosis and
BMD was performed, using chi-square and multivariable logistic regression. Other
variables included predisposing factors (gender, age and race/ethnicity),
enabling factors (marital status, education, poverty status and health insurance)
and lifestyle/behavioral factors (perceived health status, smoking, alcohol
intake, physical activity and body mass index). RESULTS: Overall, 13.5% had
fluorosis; 6.8% with fluorosis and 9.8% without fluorosis had low lumbar spine
BMD. Multivariable analysis found there was not a statistically significant
association between fluorosis and lumbar spine BMD (adjusted odds ratio=0.82; 95%
CI (0.43. 1.56)). CONCLUSION: Dental fluorosis and lumbar spine BMD were not
found to be associated in a sample of adults.
PMID- 24357569
TI - Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients
with Wolf-Hirschhorn syndrome.
AB - Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the
distal 4p chromosome, characterized by craniofacial features, growth impairment,
intellectual disability, and seizures. Although genotype-phenotype correlation
studies have previously been published, several important issues remain to be
elucidated including seizure severity. We present detailed clinical and molecular
cytogenetic findings from a microarray and fluorescence in situ hybridization
(FISH)-based genotype-phenotype analysis of 22 Japanese WHS patients, the first
large non-Western series. 4p deletions were terminal in 20 patients and
interstitial in two, with deletion sizes ranging from 2.06 to 29.42 Mb. The new
Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and
duplication of other chromosomal regions occurred in four. Complex mosaicism was
identified in two cases: two different 4p terminal deletions; a simple 4p
terminal deletion and an unbalanced translocation with the same 4p breakpoint.
Seizures began in infancy in 33% (2/6) of cases with small (<6 Mb) deletions and
in 86% (12/14) of cases with larger deletions (>6 Mb). Status epilepticus
occurred in 17% (1/6) with small deletions and in 87% (13/15) with larger
deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were
more prevalent in those with larger deletions. A new susceptible region for
seizure occurrence is suggested between 0.76 and 1.3 Mb from 4 pter, encompassing
CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The
usefulness of bromide therapy for seizures and additional clinical features
including hypercholesterolemia are also described.
PMID- 24357570
TI - Biological vulnerability to depression: linked structural and functional brain
network findings.
AB - BACKGROUND: Patients in recovery following episodes of major depressive disorder
(MDD) remain highly vulnerable to future recurrence. Although psychological
determinants of this risk are well established, little is known about associated
biological mechanisms. Recent work has implicated the default mode network (DMN)
in this vulnerability but specific hypotheses remain untested within the high
risk, recovered state of MDD. AIMS: To test the hypothesis that there is
excessive DMN functional connectivity during task performance within recovered
state MDD and to test for connected DMN cortical gyrification abnormalities.
METHOD: A multimodal structural and functional magnetic resonance imaging (fMRI)
study, including task-based functional connectivity and cortical folding
analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy
controls. RESULTS: The MDD group showed significant task-based DMN
hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral
precuneus). CONCLUSIONS: This is the first evidence of connected structural and
functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses
on biological-level vulnerability.
PMID- 24357571
TI - Lifetime affect and midlife cognitive function: prospective birth cohort study.
AB - BACKGROUND: Recurrent affective problems are predictive of cognitive impairment,
but the timing and directionality, and the nature of the cognitive impairment,
are unclear. AIMS: To test prospective associations between life-course affective
symptoms and cognitive function in late middle age. METHOD: A total of 1668 men
and women were drawn from the Medical Research Council National Survey of Health
and Development (the British 1946 birth cohort). Longitudinal affective symptoms
spanning age 13-53 years served as predictors; outcomes consisted of self
reported memory problems at 60-64 years and decline in memory and information
processing from age 53 to 60-64 years. RESULTS: Regression analyses revealed no
clear pattern of association between longitudinal affective symptoms and decline
in cognitive test scores, after adjusting for gender, childhood cognitive
ability, education and midlife socioeconomic status. In contrast, affective
symptoms were strongly, diffusely and independently associated with self-reported
memory problems. CONCLUSIONS: Affective symptoms are more clearly associated with
self-reported memory problems in late midlife than with objectively measured
cognitive performance.
PMID- 24357572
TI - Corpus callosum changes in euthymic bipolar affective disorder.
AB - BACKGROUND: Changes in corpus callosum area and thickness have been reported in
bipolar disorder. Imaging and limited neuropathological data suggest possible
abnormalities in myelination and/or glial function. AIMS: To compare corpus
callosum area, thickness and magnetic resonance imaging (MRI) T1 signal intensity
in patients with bipolar disorder and healthy controls. METHOD: A total of 48
patients with euthymic bipolar disorder and 46 healthy controls underwent MRI
analysis of callosal midsagittal area, callosal thickness and T1 signal
intensity. RESULTS: The bipolar group had smaller overall and subregional
callosal areas and correspondingly reduced callosal width than the control group.
Age correlated negatively with callosal area in the control group but not in the
bipolar group. Signal intensity was higher in women than in men in both groups.
Signal intensity was reduced in women, but not in men, in the bipolar group.
CONCLUSIONS: Observed differences probably relate to diagnosis rather than mood
state and bipolar disorder appears to result in morphometric change that
overrides changes seen in normal ageing. Intensity changes are consistent with
possible altered myelination or glial function. A gender-dependent factor appears
to operate and to interact with diagnosis.
PMID- 24357573
TI - Psychiatric assessment of mood instability: qualitative study of patient
experience.
AB - BACKGROUND: Mood instability is a common reason for psychiatric referral. Very
little is known about how patients with unstable mood experience assessment and
diagnosis. AIMS: To investigate the experiences of assessment and diagnosis among
patients with mood instability and to suggest improvements to this process.
METHOD: Qualitative study, gathering data through individual interviews with 28
people experiencing mood instability and receiving a psychiatric assessment in
secondary care. RESULTS: Participants described the importance of receiving an
explanation for their symptoms; the value of a good interpersonal relationship
with their clinician(s); being listened to and acknowledged; and being involved
in and informed about clinical decisions. These needs were not, however,
consistently met. Receiving a psychiatric diagnosis, including a diagnosis of
bipolar disorder or borderline personality disorder, evoked both positive and
negative responses among participants, relating to stigma, personal understanding
and responsibility, prognosis and treatment. CONCLUSIONS: Patients with mood
instability seek explanation for their symptoms and difficulties, empathetic care
and consistent support as much as cure. Clinicians may incorrectly assume what
patients' attitudes towards diagnosis are, a mismatch which may hamper the
development of a strong therapeutic relationship. Clear, patient-centred
communication, which acknowledges the patient's experience, may result in greater
patient engagement and satisfaction.
PMID- 24357574
TI - One-day cognitive-behavioural therapy self-confidence workshops for people with
depression: randomised controlled trial.
AB - BACKGROUND: Despite its high prevalence, help-seeking for depression is low.
AIMS: To assess the effectiveness and cost-effectiveness of 1-day cognitive
behavioural therapy (CBT) self-confidence workshops in reducing depression.
Anxiety, self-esteem, prognostic indicators as well as access were also assessed.
METHOD: An open randomised controlled trial (RCT) waiting list control design
with 12-week follow-up was used (trial registration: ISRCTN26634837). A total of
459 adult participants with depression (Beck Depression Inventory (BDI) scores of
>= 14) self-referred and 382 participants (83%) were followed up. RESULTS: At
follow-up, experimental and control participants differed significantly on the
BDI, with an effect size of 0.55. Anxiety and self-esteem also differed. Of those
who participated, 25% were GP non-consulters and 32% were from Black and minority
ethnic groups. Women benefited more than men on depression scores. The
intervention has a 90% chance of being considered cost-effective if a depression
free day is valued at L14. CONCLUSIONS: Self-confidence workshops appear
promising in terms of clinical effectiveness, cost-effectiveness and access by
difficult-to-engage groups.
PMID- 24357575
TI - Multidimensional Treatment Foster Care for Adolescents in English care:
randomised trial and observational cohort evaluation.
AB - BACKGROUND: Children in care often have poor outcomes. There is a lack of
evaluative research into intervention options. AIMS: To examine the efficacy of
Multidimensional Treatment Foster Care for Adolescents (MTFC-A) compared with
usual care for young people at risk in foster care in England. METHOD: A two-arm
single (assessor) blinded randomised controlled trial (RCT) embedded within an
observational quasi-experimental case-control study involving 219 young people
aged 11-16 years (trial registration: ISRCTN 68038570). The primary outcome was
the Child Global Assessment Scale (CGAS). Secondary outcomes were ratings of
educational attendance, achievement and rate of offending. RESULTS: The MTFC-A
group showed a non-significant improvement in CGAS outcome in both the randomised
cohort (n = 34, adjusted mean difference 1.3, 95% CI -7.1 to 9.7, P = 0.75) and
in the trimmed observational cohort (n = 185, adjusted mean difference 0.95, 95%
CI -2.38 to 4.29, P = 0.57). No significant effects were seen in secondary
outcomes. There was a possible differential effect of the intervention according
to antisocial behaviour. CONCLUSIONS: There was no evidence that the use of MTFC
A resulted in better outcomes than usual care. The intervention may be more
beneficial for young people with antisocial behaviour but less beneficial than
usual treatment for those without.
PMID- 24357576
TI - Transition to schizophrenia in acute and transient psychotic disorders.
AB - BACKGROUND: The diagnostic category of acute and transient psychotic disorders
(ATPD) was introduced in ICD-10. Subsequent studies have called into question its
validity and reliability. AIMS: To determine the pattern of diagnostic revision
to schizophrenia in first-ever diagnosed ATPD. METHOD: Using data drawn from the
Scottish Morbidity Record, we estimated incidence and diagnostic change in first
ever diagnosed ATPD in Scottish hospitals between January 1997 and December 2010
(n = 2923). RESULTS: The average incidence of ATPD was 4.1 per 100 000 population
per year. Diagnostic stability was estimated at 53.9% over an average of
approximately 4 years of observation. The most common diagnostic shift was to
schizophrenia (12.6%), over an average of 1.7 years. Estimates of the transition
risks for schizophrenia were 80% at 2.8 years and 90% at 4.6 years. Longer first
admission to hospital, younger age at onset and male gender were associated with
increased risk and earlier development of schizophrenia. CONCLUSIONS: Routinely
collected data suggest that approximately one in eight individuals with first
ever diagnosed ATPD will develop schizophrenia within 3-5 years. Those at high
risk of transition may benefit from monitoring for possible diagnostic change.
PMID- 24357577
TI - Self-assembling stereocomplex nanoparticles by enantiomeric poly(gamma-glutamic
acid)-poly(lactide) graft copolymers as a protein delivery carrier.
AB - Amphiphilic graft copolymers, poly(gamma-glutamic acid)-graft-poly(lactide)
(gamma-PGA-g-PLA) bearing pendent poly(L-lactide) (PLLA) or poly(D-lactide)
(PDLA) of different main chain lengths and grafting degrees, self-assemble in
aqueous solution to form monodispersed stereocomplex nanoparticles (NPs). The
mean diameter and degree of crystallinity of these stereocomplex NPs can be
controlled by changing the grafting degree of the copolymers or the preparation
methods. Moreover, the stereocomplex NPs exhibit a lower critical aggregation
concentration as well as stronger thermodynamic stability compared with the
corresponding isomer NPs. The surface-functionalized ability and protein
encapsulation capacity of the stereocomplex NPs as potential targeting protein
carriers are evaluated. Furthermore, these stereocomplex NPs have strong kinetic
stability and can be expected to serve as stable delivery vehicles for
pharmaceutical and biomedical applications.
PMID- 24357578
TI - Longitudinal assessment of cognition and T2-hyperintensities in NF1: an 18-year
study.
AB - The developmental course of cognitive deficits in individuals with
neurofibromatosis type 1 (NF1) is unclear. The objectives of this study were to
determine the natural history of cognitive function and MRI T2-hyperintesities
(T2H) from childhood to adulthood and to examine whether the presence of discrete
T2H in childhood can predict cognitive performance in adulthood. We present
cognitive and structural neuroimaging data from 18 patients with NF1 and five
sibling controls assessed prospectively across an 18-year period. Longitudinal
analyses revealed a significant increase in general cognitive function in
patients with NF1 over the study period. Improvements were limited to individuals
with discrete T2H in childhood. Patients without lesions in childhood exhibited a
stable profile. The number of T2H decreased over time, particularly discrete
lesions. Lesions located within the cerebral hemispheres and deep white matter
were primarily stable, whereas those located in the basal ganglia, thalamus and
brainstem tended to resolve. Our results support the hypothesis that resolution
of T2H is accompanied by an improvement in general cognitive performance,
possibly as a result of increased efficiency within white matter tracts.
PMID- 24357579
TI - Muscle mass and mortality in chronic liver disease: the impact of testosterone.
PMID- 24357580
TI - Diagnostic dilemma of unicystic ameloblastoma: novel parameters to differentiate
unicystic ameloblastoma from common odontogenic cysts.
AB - AIM: Diagnostic criteria that have been specified for unicystic ameloblastomas
(UAs) are not always helpful to differentiate these cystic tumors from common
odontogenic cysts. The aim of this study therefore was to identify additional
histopathological features (other than the features considered for the diagnosis
of UA at present) that would be helpful to differentiate UA from odontogenic
cysts. METHODS: One hundred histopathologically confirmed unicystic
ameloblastomas and 20 cases each of radicular, inflamed dentigerous and non
inflamed dentigerous cysts were selected. Histopathological features of the UAs
that are not used as diagnostic criteria at present were identified. RESULTS:
Hyperplastic arcading epithelial proliferations with stellate-reticulum-like and
vacuolated cells were always seen associated with inflammation in odontogenic
cysts, while in UA plexiform-like areas were also seen without inflammation (P <
0.001). In addition, a spiky rete pattern was observed in non-inflamed UA while
this pattern was observed only in inflamed odontogenic cysts. Furthermore, spiky
retes together with subepithelial hyalinization were usually observed in UAs
while only subepithelial hyalinization was observed in non-inflamed dentigerous
cysts. CONCLUSIONS: Combinations of histopathological features were identified to
differentiate non-inflamed UA from common odontogenic cysts. However, presence of
inflammatory changes in UA precludes the use of features identified in the
present study for diagnostic purposes.
PMID- 24357582
TI - Low-level mesodermal somatic mutation mosaicism: late-onset craniofacial and
cervical spinal hyperostoses.
AB - Craniofacial and cervical spinal hyperostoses are rarely seen in the absence of
other abnormalities. Only seven patients with isolated cranial hyperostoses have
been reported, and only a single patient with both calvarial and cervical
vertebral hyperostoses. We report on an adult with late-onset right-sided
asymmetrical hyperostoses of the cranium, mandible, and cervical vertebrae in the
absence of an AKT1 mutation. At presentation, the patient displayed neither
generalized overgrowth nor dysregulated adipose tissue. Standard polymerase chain
reaction and Sanger sequencing of DNA extracted from formalin-fixed paraffin
embedded frontal bone and mandibular angular bone was negative for an AKT1
mutation. Though the patient's clinical manifestations did not fulfill the
consensus diagnostic criteria of Proteus syndrome, the mosaic distribution of
lesions, the sporadic occurrence, and the patient's progressive course were
consistent with a somatic mosaicism similar to that syndrome. Hence, the
patient's phenotype may have been caused by a very late mesodermal somatic
mutation during embryogenesis.
PMID- 24357581
TI - The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of
lysosomes.
AB - TMEM106B is a major risk factor for frontotemporal lobar degeneration with TDP-43
pathology. TMEM106B localizes to lysosomes, but its function remains unclear. We
show that TMEM106B knockdown in primary neurons affects lysosomal trafficking and
blunts dendritic arborization. We identify microtubule-associated protein 6
(MAP6) as novel interacting protein for TMEM106B. MAP6 over-expression inhibits
dendritic branching similar to TMEM106B knockdown. MAP6 knockdown fully rescues
the dendritic phenotype of TMEM106B knockdown, supporting a functional
interaction between TMEM106B and MAP6. Live imaging reveals that TMEM106B
knockdown and MAP6 overexpression strongly increase retrograde transport of
lysosomes in dendrites. Downregulation of MAP6 in TMEM106B knockdown neurons
restores the balance of anterograde and retrograde lysosomal transport and
thereby prevents loss of dendrites. To strengthen the link, we enhanced
anterograde lysosomal transport by expressing dominant-negative Rab7-interacting
lysosomal protein (RILP), which also rescues the dendrite loss in TMEM106B
knockdown neurons. Thus, TMEM106B/MAP6 interaction is crucial for controlling
dendritic trafficking of lysosomes, presumably by acting as a molecular brake for
retrograde transport. Lysosomal misrouting may promote neurodegeneration in
patients with TMEM106B risk variants.
PMID- 24357583
TI - Adolescent mental health and subsequent parenting: a longitudinal birth cohort
study.
AB - BACKGROUND: Adolescent mental health problems are associated with a range of
adverse outcomes in adulthood but little is known about the effects on adult
parenting practices. This study aimed to examine prospective associations between
adolescent conduct and emotional problems and subsequent parenting behaviours in
adulthood. METHODS: The study sample comprised 1110 members from the MRC National
Survey of Health and Development. Prospective data were collected from teacher
reports of conduct and emotional problems at age 13 and 15 years and adult
outcome measures of parenting included intellectual environment, cognitive
stimulation, coercive discipline, parental interest and parental aspiration.
RESULTS: In regression models adjusted for the confounding effects of social
background, cognition and education, adolescent conduct problems predicted
coercive parenting behaviours in adulthood. The effects of adolescent emotional
problems on the development of coercive discipline practices were explained by
covariates. Likewise, the inability of parents who displayed conduct problems in
adolescence to provide an intellectually stimulating home environment was fully
explained by the adjustment for education. CONCLUSIONS: Adolescents who exhibit
conduct problems are more likely to develop coercive styles of parenting.
PMID- 24357584
TI - Looking ahead: what is scholarship?
PMID- 24357585
TI - Commentary on Rosen.
PMID- 24357586
TI - Reply to Stern.
PMID- 24357587
TI - Analyzing the children of immigrants. Panel reports.
PMID- 24357588
TI - Silence, now. Panel reports.
PMID- 24357589
TI - Hysterical and obsessive-compulsive symptom patterns: are they associated with
anaclitic and introjective interpersonal profiles?
PMID- 24357590
TI - Affective processing and affect regulation: a clinical interview study.
PMID- 24357591
TI - Anal and oral word use in relation to dependency and self-criticism.
PMID- 24357592
TI - The tongue ever turns to the aching tooth: a pilot study of depressed patients'
self-preoccupation.
PMID- 24357593
TI - Hysterical and obsessional transference patterns: do they underlie the field of
neurotic symptoms?
PMID- 24357594
TI - De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two
new cases and a clinical review.
AB - Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder
characterized by craniosynostosis, distinctive craniofacial features, skeletal
abnormalities, marfanoid body habitus, aortic dilatation, and intellectual
disability. Mutations in exon 1 of SKI have recently been identified as being
responsible for approximately 90% of reported individuals diagnosed clinically
with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFbeta signaling.
Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg
syndrome is likely caused by deregulated TGFbeta signals, explaining the
considerable phenotypic overlap between these three disorders. We describe two
additional patients with exon 1 SKI mutations and review the clinical features
and literature of Shprintzen-Goldberg syndrome.
PMID- 24357595
TI - Effect of phase 1 periodontal therapy on gingival crevicular fluid levels of
matrix metalloproteinases-3 and -13 in chronic periodontitis patients.
AB - AIM: The aim of the present study was to estimate the gingival crevicular fluid
(GCF) levels of matrix metalloproteinases (MMP)-3 and -13 in periodontally
healthy controls and chronic periodontitis (CP) patients, and also to investigate
the effect of phase 1 periodontal therapy on MMP-3 and -13 levels in CP patients.
METHODS: Fifty-five systemically-healthy patients were divided into two groups:
group 1 (healthy) and group 2 (CP). The recording of clinical parameters and GCF
sampling was done at baseline for both groups and again at 6 weeks post-therapy
for group 2. The MMP level was determined by ELISA. RESULTS: A significant
increase in the mean MMP-3 and -13 was found between healthy and CP patients.
There was a statistically-significant reduction of GCF MMP-3 and -13
concentration after periodontal therapy in the CP group. A positive correlation
was found between clinical parameters and GCF MMP-3 and -13 levels. CONCLUSIONS:
A lower concentration of GCF MMP-3 and -13 was found in healthy patients, and a
higher concentration was noted for CP patients, which was reduced after
periodontal therapy. This indicates the important role played by these MMP in
periodontal destruction. Thus, MMP-3 and -13 could be used as inflammatory
biomarkers in diagnosing periodontal disease severity.
PMID- 24357596
TI - Doctor, is a CT scan safe for my child?
PMID- 24357597
TI - Post-marketing surveillance study with iodixanol in 20 185 Chinese patients from
routine clinical practices.
AB - OBJECTIVE: To determine the incidence of immediate and delayed adverse drug
reactions (ADRs), and to assess patient discomfort following administration of
iodixanol during imaging examinations in routine clinical practice. METHODS: A
total of 20 185 patients across 95 clinical centres were enrolled in a
prospective post-marketing surveillance registry with iodixanol. Patients were
monitored for occurrence of ADRs immediately following iodixanol administration
and for up to 7 days after administration. RESULTS: The overall rate of ADRs was
1.52%, of which 0.58% was immediate and 0.97% was delayed onset. Two patients had
non-fatal serious ADRs (0.01%). The ADRs were significantly more common in
patients who underwent contrast-enhanced CT/coronary CT angiography vs others (p
< 0.001), in those receiving pre-heated iodixanol vs non-heating (p < 0.001), in
those aged 70 years or younger (p < 0.001), in those in whom a power injector was
used for contrast delivery (p < 0.001) and in those with a history of an allergic
reaction to contrast (p = 0.024). Multivariate analysis showed that female
gender, intravenous route of contrast injection, body weight >= 80 kg, age less
than 65 years, contrast flow rate >= 4 ml s-1 and prior reaction to iodinated
contrast medium were all significant and independent contributors to ADRs. Pre
treatment contrast volume and history of cardiac disease, gout, hypertension,
diabetes mellitus or asthma did not affect the rate of ADRs. Discomfort was
generally mild, with 94.8% of patients reporting a composite score of 0-3.
CONCLUSION: The safety of iodixanol in routine clinical practice was shown to be
similar to the published safety profiles of other non-ionic iodinated contrast
agents. Patient discomfort during administration was mild or absent in most
patients. ADVANCES IN KNOWLEDGE: The major strength of this study is that it
included 20 185 patients enrolled in various types of imaging examinations. The
safety profile of iodixanol was comparable to previously published work.
PMID- 24357598
TI - Novel association of neurofibromatosis type 1-causing mutations in families with
neurofibromatosis-Noonan syndrome.
AB - Neurofibromatosis-Noonan syndrome (NFNS) is a rare condition with clinical
features of both neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). All
three syndromes belong to the RASopathies, which are caused by dysregulation of
the RAS-MAPK pathway. The major gene involved in NFNS is NF1, but co-occurring
NF1 and PTPN11 mutations in NFNS have been reported. Knowledge about possible
involvement of additional RASopathy-associated genes in NFNS is, however, very
limited. We present a comprehensive clinical and molecular analysis of eight
affected individuals from three unrelated families displaying features of NF1 and
NFNS. The genetic etiology of the clinical phenotypes was investigated by
mutation analysis, including NF1, PTPN11, SOS1, KRAS, NRAS, BRAF, RAF1, SHOC2,
SPRED1, MAP2K1, MAP2K2, and CBL. All three families harbored a heterozygous NF1
variant, where the first family had a missense variant, c.5425C>T;p.R1809C, the
second family a recurrent 4bp-deletion, c.6789_6792delTTAC;p.Y2264Tfs*6, and the
third family a splice-site variant, c.2991-1G>A, resulting in skipping of exon 18
and an in-frame deletion of 41 amino acids. These NF1 variants have all
previously been reported in NF1 patients. Surprisingly, both c.6789_6792delTTAC
and c.2991-1G>A are frequently associated with NF1, but association to NFNS has,
to our knowledge, not previously been reported. Our results support the notion
that NFNS represents a variant of NF1, genetically distinct from NS, and is
caused by mutations in NF1, some of which also cause classical NF1. Due to
phenotypic overlap between NFNS and NS, we propose screening for NF1 mutations in
NS patients, preferentially when cafe-au-lait spots are present.
PMID- 24357599
TI - Translation elongation can control translation initiation on eukaryotic mRNAs.
AB - Synonymous codons encode the same amino acid, but differ in other biophysical
properties. The evolutionary selection of codons whose properties are optimal for
a cell generates the phenomenon of codon bias. Although recent studies have shown
strong effects of codon usage changes on protein expression levels and cellular
physiology, no translational control mechanism is known that links codon usage to
protein expression levels. Here, we demonstrate a novel translational control
mechanism that responds to the speed of ribosome movement immediately after the
start codon. High initiation rates are only possible if start codons are
liberated sufficiently fast, thus accounting for the observation that fast codons
are overrepresented in highly expressed proteins. In contrast, slow codons lead
to slow liberation of the start codon by initiating ribosomes, thereby
interfering with efficient translation initiation. Codon usage thus evolved as a
means to optimise translation on individual mRNAs, as well as global optimisation
of ribosome availability.
PMID- 24357600
TI - TAP46 plays a positive role in the ABSCISIC ACID INSENSITIVE5-regulated gene
expression in Arabidopsis.
AB - TAP46 is a protein phosphatase2A (PP2A)-associated protein that regulates PP2A
activity in Arabidopsis (Arabidopsis thaliana). To study how PP2A is involved in
abscisic acid (ABA) signaling in plants, we studied the function of TAP46 in ABA
regulated seed maturation and seedling development. Expression of TAP46 coincides
with the action of ABA in developing seeds and during seed germination, and the
TAP46 transcript reaches to the highest level in mature seeds. Real-time
polymerase chain reaction analysis indicates that external ABA can increase TAP46
transcript level transiently during seed germination. Overexpression of TAP46
increases plant sensitivity to ABA, while tap46 knockdown mutants are less
sensitive to ABA during seed germination, suggesting that TAP46 functions
positively in ABA signaling. Overexpression of TAP46 also leads to lower PP2A
activity, while tap46-1 knockdown mutant displays higher PP2A activity,
suggesting that TAP46 negatively regulates PP2A activity in Arabidopsis. Both
TAP46 and PP2A interact with the ABA-regulated transcription factor ABA
INSENSITIVE5 (ABI5) in vivo, and TAP46's binding to ABI5 can stabilize ABI5.
Furthermore, TAP46's binding to the phosphorylated ABI5 may prevent PP2A or PP2A
like protein phosphatases from removing the phosphate from ABI5, thereby
maintaining ABI5 in its active form. Overexpression of TAP46 and inhibition of
activities of PP2A or PP2A-like protein phosphatases can increase transcript
levels of several ABI5-regulated genes, suggesting that TAP46 is a positive
factor in the ABA-regulated gene expression in Arabidopsis.
PMID- 24357601
TI - Interaction of photoperiod and vernalization determines flowering time of
Brachypodium distachyon.
AB - Timing of flowering is key to the reproductive success of many plants. In
temperate climates, flowering is often coordinated with seasonal environmental
cues such as temperature and photoperiod. Vernalization is an example of
temperature influencing the timing of flowering and is defined as the process by
which a prolonged exposure to the cold of winter results in competence to flower
during the following spring. In cereals, three genes (VERNALIZATION1 [VRN1],
VRN2, and FLOWERING LOCUS T [FT]) have been identified that influence the
vernalization requirement and are thought to form a regulatory loop to control
the timing of flowering. Here, we characterize natural variation in the
vernalization and photoperiod responses in Brachypodium distachyon, a small
temperate grass related to wheat (Triticum aestivum) and barley (Hordeum
vulgare). Brachypodium spp. accessions display a wide range of flowering
responses to different photoperiods and lengths of vernalization. In addition, we
characterize the expression patterns of the closest homologs of VRN1, VRN2 (VRN2
like [BdVRN2L]), and FT before, during, and after cold exposure as well as in
different photoperiods. FT messenger RNA levels generally correlate with
flowering time among accessions grown in different photoperiods, and FT is more
highly expressed in vernalized plants after cold. VRN1 is induced by cold in
leaves and remains high following vernalization. Plants overexpressing VRN1 or FT
flower rapidly in the absence of vernalization, and plants overexpressing VRN1
exhibit lower BdVRN2L levels. Interestingly, BdVRN2L is induced during cold,
which is a difference in the behavior of BdVRN2L compared with wheat VRN2 during
cold.
PMID- 24357603
TI - Focal dermal hypoplasia without focal dermal hypoplasia.
AB - Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome) is an X-linked dominant
disorder affecting mainly tissues of ectodermal and mesodermal origin. The
phenotype is characterized by hypoplastic linear skin lesions, eye malformations,
hair and teeth anomalies, and multiple limbs malformations. The disorder is
caused by PORCN mutations. Here we describe a mother and daughter with FDH in
whom a c.938T>G in PORCN was detected. Neither of the two had FDH, but otherwise
the phenotype was classical. Focal skin hypoplasia is a hallmark of FDH but the
present family indicates that FDH should also be considered in absence of this
skin manifestation.
PMID- 24357602
TI - Analyses of tomato fruit brightness mutants uncover both cutin-deficient and
cutin-abundant mutants and a new hypomorphic allele of GDSL lipase.
AB - The cuticle is a protective layer synthesized by epidermal cells of the plants
and consisting of cutin covered and filled by waxes. In tomato (Solanum
lycopersicum) fruit, the thick cuticle embedding epidermal cells has crucial
roles in the control of pathogens, water loss, cracking, postharvest shelf-life,
and brightness. To identify tomato mutants with modified cuticle composition and
architecture and to further decipher the relationships between fruit brightness
and cuticle in tomato, we screened an ethyl methanesulfonate mutant collection in
the miniature tomato cultivar Micro-Tom for mutants with altered fruit
brightness. Our screen resulted in the isolation of 16 glossy and 8 dull mutants
displaying changes in the amount and/or composition of wax and cutin, cuticle
thickness, and surface aspect of the fruit as characterized by optical and
environmental scanning electron microscopy. The main conclusions on the
relationships between fruit brightness and cuticle features were as follows: (1)
screening for fruit brightness is an effective way to identify tomato cuticle
mutants; (2) fruit brightness is independent from wax load variations; (3) glossy
mutants show either reduced or increased cutin load; and (4) dull mutants display
alterations in epidermal cell number and shape. Cuticle composition analyses
further allowed the identification of groups of mutants displaying remarkable
cuticle changes, such as mutants with increased dicarboxylic acids in cutin.
Using genetic mapping of a strong cutin-deficient mutation, we discovered a novel
hypomorphic allele of GDSL lipase carrying a splice junction mutation, thus
highlighting the potential of tomato brightness mutants for advancing our
understanding of cuticle formation in plants.
PMID- 24357604
TI - Efficacy of tooth bleaching with the prior application of a desensitizing agent.
AB - AIM: In the present study, we evaluated the efficacy of bleaching on enamel and
opposite dentin surfaces using 35% hydrogen peroxide (HP) with the prior
application of a desensitizing agent. METHODS: Thirty bovine dental fragments,
with thicknesses of 1 mm enamel and 1.75 mm dentin, were stained in a solution of
black tea. The fragments were randomly divided into three groups (n = 10)
according to the following protocols: (a) 2% neutral fluoride + bleaching; (b)
desensitizing agent + bleaching; and (c) without desensitizer + bleaching. The
bleaching efficacy was evaluated four times: after staining with tea (baseline)
and after each of the 3 weeks of bleaching, by means of the CIE Lab method using
a reflectance spectrophotometer. The data coordinate L* was evaluated by an
analysis of repeated measures with PROC MIXED and Tukey-Kramer's test. The DeltaE
values were subjected to anova and Tukey's test (alpha = 0.05). RESULTS: The 35%
HP treatment showed greater efficacy on deep dentin after removal of the enamel
stains, with increasing means during all times in all treatments. CONCLUSION: The
use of a desensitizing agent prior to the bleaching session did not affect the
mechanism of action of 35% HP with regard to tooth depth.
PMID- 24357605
TI - Patient with three euchromatic supernumerary marker chromosomes derived from
chromosomes 1, 12, and 18: characterization and evaluation of the aberrations.
AB - The genetic relevance of small supernumerary marker chromosomes (sSMCs) depends
on their content of euchromatin. In case of mosaicism, the phenotype of the
carrier furthermore is influenced by the distribution of the marker in the body.
In the majority of reported cases no correlation of the degree of mosaicism in
the tissue(s) analyzed and the phenotype could be detected. In particular, non
acrocentric derived sSMCs show a strong tendency to appear in mosaic state
irrespective of the clinical picture. We present a patient with cognitive
disability and mild craniofacial dysmorphisms with mosaicism of three different
autosomal marker chromosomes. The extra chromosomes were analyzed by a
combination of SNP array and a variety of fluorescence in situ hybridization
(FISH) probes. All three markers were identified as ring chromosomes containing
different amounts of euchromatic material derived from chromosome 1 (1p12 ->
q21), 12 (12p13.1 -> q13.11) and 18 (18p11.21 -> q11.2). The size and the
frequency of the sSMCs were strikingly different, besides, we observed an unequal
combination of the three derivates.
PMID- 24357606
TI - Permethrin resistance variation and susceptible reference line isolation in a
field population of the mosquito, Culex quinquefasciatus (Diptera: Culicidae).
AB - This study examines the genetic variations and mechanisms involved in the
development of permethrin resistance in individual mosquitoes from a field
population of Culex quinquefasciatus, HAmCq(G0) , and characterizes susceptible
reference lines of mosquitoes with a similar genetic background to the field
HAmCq(G0) strain. Six upregulated cytochrome P450 genes, CYP9M10, CYP9J34,
CYP6P14, CYP9J40, CYP6AA7, and CYP4C52v1, previously identified as being
upregulated in the larvae of resistant HAmCq(G8) mosquitoes were examined in the
larvae of 3 strains (susceptible S-Lab, parental HAmCq(G0) and permethrin
selected highly resistant HAmCq(G8) ) and 8 HAmCq(G0) single-egg raft colonies,
covering a range of levels of susceptibility/resistance to permethrin and
exhibiting different variations in the expression of A and/or T alleles at the L
to-F kdr locus of the sodium channel. The 2 lines with the lowest tolerance to
permethrin and bearing solely the susceptible A allele at the L-to-F kdr locus of
the sodium channels, from colonies Cx_SERC5 and Cx_SERC8, showed lower or similar
levels of all 6 of the P450 genes tested compared with the S-Lab strain,
suggesting that these 2 lines could be used as the reference mosquitoes in future
studies characterizing insecticide resistance in HAmCq mosquitoes. This study
also provides a detailed investigation of the mechanisms involved in insecticide
resistance in individuals within a population: individuals with elevated levels
of resistance to permethrin all displayed one or more potential resistance
mechanisms-either elevated levels of P450 gene expression, or L-to-F mutations in
the sodium channel, or both.
PMID- 24357607
TI - Fraser syndrome due to mutations in GRIP1--clinical phenotype in two families and
expansion of the mutation spectrum.
PMID- 24357609
TI - "How often? How much? Where from?" knowledge, attitudes, and practices of mothers
and health workers to iron supplementation program for children under five in
rural Tamil Nadu, south India.
AB - Iron deficiency anemia (IDA) affects 70% of under-5 children in India. The
primary prevention strategy is regular iron supplementation. Little is known
about what helps families adhere to daily iron supplementation. Our study
explored the knowledge, attitudes, and practices of mothers and village health
workers (VHWs) involved in a community health program in one hill district of
Tamil Nadu. We conducted 30 semistructured interviews and 3 group discussions
involving mothers, VHWs, and community stakeholders. Knowledge of IDA was
widespread, yet no children were receiving the iron supplementation as
recommended. The main determinants to adherence included the perception of its
need, the ease of access, and the activity of VHWs. Preventive care requiring
daily supplements is challenging. Our study suggests that increasing community
awareness of mild anemia, simplifying dosage instructions, and further
strengthening the supportive environment for VHWs would help in reducing the
prevalence of IDA.
PMID- 24357608
TI - The Arabidopsis PEPR pathway couples local and systemic plant immunity.
AB - Recognition of microbial challenges leads to enhanced immunity at both the local
and systemic levels. In Arabidopsis, EFR and PEPR1/PEPR2 act as the receptor for
the bacterial elongation factor EF-Tu (elf18 epitope) and for the endogenous
PROPEP-derived Pep epitopes, respectively. The PEPR pathway has been described to
mediate defence signalling following microbial recognition. Here we show that
PROPEP2/PROPEP3 induction upon pathogen challenges is robust against jasmonate,
salicylate, or ethylene dysfunction. Comparative transcriptome profiling between
Pep2- and elf18-treated plants points to co-activation of otherwise antagonistic
jasmonate- and salicylate-mediated immune branches as a key output of PEPR
signalling. Accordingly, as well as basal defences against hemibiotrophic
pathogens, systemic immunity is reduced in pepr1 pepr2 plants. Remarkably,
PROPEP2/PROPEP3 induction is essentially restricted to the pathogen challenge
sites during pathogen-induced systemic immunity. Localized Pep application
activates genetically separable jasmonate and salicylate branches in systemic
leaves without significant PROPEP2/PROPEP3 induction. Our results suggest that
local PEPR activation provides a critical step in connecting local to systemic
immunity by reinforcing separate defence signalling pathways.
PMID- 24357610
TI - Mortality in Cambodia: an 18-month prospective community-based surveillance of
all-age deaths using verbal autopsies.
AB - To estimate the 2009-2010 death rates, causes, and patterns of mortality in rural
Cambodia, we conducted active, population-based death surveillance in 25 rural
villages of Cambodia from March 2009 to August 2010. Among the population of
28,053 under surveillance, 280 deaths were reported and explored by physician
certified verbal autopsies, using the International Classification of Diseases
10, yielding an overall mortality rate (MR) of 6.7/1000 persons-year (95% CI 5.74
7.68). The MR was 39.1/1000 live births for those younger than 5 years old.
Infants accounted for 5.4% of all deaths. In children younger than 5 years,
infectious and parasitic diseases were the leading causes of death. In children 5
to 14 years, 3 out of 4 deaths were due to injuries. Adult deaths were mainly
attributed to noncommunicable diseases (52%). We conclude that this rural
population is facing a substantial burden of noncommunicable diseases while still
struggling with infectious diseases, respiratory diseases in particular.
PMID- 24357611
TI - Mechanisms underlying subunit independence in pyramidal neuron dendrites.
AB - Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate
local spikes, which has led to the proposal that their dendrites act as
independent computational subunits within a multilayered processing scheme.
However, when a PN is strongly activated, back-propagating action potentials
(bAPs) sweeping outward from the soma synchronize dendritic membrane potentials
many times per second. How PN dendrites maintain the independence of their
voltage-dependent computations, despite these repeated voltage resets, remains
unknown. Using a detailed compartmental model of a layer 5 PN, and an improved
method for quantifying subunit independence that incorporates a more accurate
model of dendritic integration, we first established that the output of each
dendrite can be almost perfectly predicted by the intensity and spatial
configuration of its own synaptic inputs, and is nearly invariant to the rate of
bAP-mediated "cross-talk" from other dendrites over a 100-fold range. Then,
through an analysis of conductance, voltage, and current waveforms within the
model cell, we identify three biophysical mechanisms that together help make
independent dendritic computation possible in a firing neuron, suggesting that a
major subtype of neocortical neuron has been optimized for layered,
compartmentalized processing under in-vivo-like spiking conditions.
PMID- 24357613
TI - Report of a patient with Temple-Baraitser syndrome.
PMID- 24357612
TI - Knowledge of and attitudes towards HIV/AIDS: a survey among dental students in
Ajman, UAE.
AB - AIM: Encounters between dentists and patients with HIV/AIDS are bound to rise due
to increased prevalence and emerging new treatments. This study assessed dental
students' knowledge about transmission and oral manifestations of HIV/AIDS, and
their attitudes towards patients regarding obligations to treat. METHODS: Out of
109 students in 4 years of a 6-year dental undergraduate program, 106 responded
to a questionnaire on knowledge of and attitudes towards HIV/AIDS. Knowledge and
attitude scores were analyzed with Kruskal-Wallis one-way anova and the gender
differences with the Wilcoxon signed-rank test. RESULTS: The median score for
students' overall knowledge was 39.5 (67%; maximum possible 59). The median
knowledge scores for males and females were 38 and 40 respectively, although the
difference was not statistically significant. The knowledge levels in Year 4
(42.5 +/- 4.7), Year 3 (44 +/- 6.5), and Year 2 (42 +/- 5.8), were similar but
significantly higher than in Year 1 (33 +/- 7.9; P < 0.01). The median attitude
score was 14 out of 24, with no significant differences within genders and years
of study. Although the level of knowledge of the senior students was higher than
that of the first years, the negative attitudes remained largely unchanged.
CONCLUSIONS: Appropriate educational programs may alter the misconceptions and
the negative attitudes.
PMID- 24357614
TI - Loss attention in a dual-task setting.
AB - The positive effect of losses on performance has been explained as stemming from
the increased weighting of losses relative to gains. We examine an alternative
possibility whereby this effect is mediated by attentional processes. Using the
dual-task paradigm, we expected that positive effects of losses on performance
would emerge under attentional scarcity and diffuse to a concurrently presented
task. In Study 1, decision performance was compared for a task that involved
either gains or losses and was performed either alone or as a secondary task. The
results showed a significant 40% improvement in performance in the loss
condition, but only under conditions of resource scarcity, when the task was a
secondary one. In Study 2, the same task was presented as a primary task. Again,
losses were associated with improved performance in the secondary task. Given
that this secondary task did not include losses, these findings demonstrate an
attentional spillover effect.
PMID- 24357615
TI - Conditional automaticity in response selection: contingent involuntary response
inhibition with varied stimulus-response mapping.
AB - One aspect of effective cognitive control is the ability to withhold contextually
inappropriate responses. The inhibition of a response can be elicited by a goal
relevant stop signal, which has been characterized as a voluntary cognitive
process. Cases in which inhibition is triggered automatically by a stimulus have
been reported but are limited to instances in which the withholding of a response
is associated with the same stimulus over repeated trials, which reflects the
gradual emergence of automaticity through associative learning. Findings such as
these suggest that inhibitory control is driven by two dissociable mechanisms,
one that is flexible but deliberate and another that is automatic but inflexibly
learned. In the present study, we showed that response inhibition can be
involuntarily triggered when stimulus-response mapping varies unpredictably,
without contributions from associative learning. Our findings demonstrate that
automatic response inhibition can be flexibly conditioned on top-down goals,
which has broad implications for theories of cognitive control.
PMID- 24357616
TI - Saving in cycles: how to get people to save more money.
AB - Low personal savings rates are an important social issue in the United States. We
propose and test one particular method to get people to save more money that is
based on the cyclical time orientation. In contrast to conventional, popular
methods that encourage individuals to ignore past mistakes, focus on the future,
and set goals to save money, our proposed method frames the savings task in
cyclical terms, emphasizing the present. Across the studies, individuals who used
our proposed cyclical savings method, compared with individuals who used a linear
savings method, provided an average of 74% higher savings estimates and saved an
average of 78% more money. We also found that the cyclical savings method was
more efficacious because it increased implementation planning and lowered future
optimism regarding saving money.
PMID- 24357617
TI - Self-affirmation among the poor: cognitive and behavioral implications.
AB - The poor are universally stigmatized. The stigma of poverty includes being
perceived as incompetent and feeling shunned and disrespected. It can lead to
cognitive distancing, diminish cognitive performance, and cause the poor to
forego beneficial programs. In the present research, we examined how self
affirmation can mitigate the stigma of poverty through randomized field
experiments involving low-income individuals at an inner-city soup kitchen.
Because of low literacy levels, we used an oral rather than written affirmation
procedure, in which participants verbally described a personal experience that
made them feel successful or proud. Compared with nonaffirmed participants,
affirmed individuals exhibited better executive control, higher fluid
intelligence, and a greater willingness to avail themselves of benefits programs.
The effects were not driven by elevated positive mood, and the same intervention
did not affect the performance of wealthy participants. The findings suggest that
self-affirmation can improve the cognitive performance and decisions of the poor,
and it may have important policy implications.
PMID- 24357618
TI - Extremely rapid acclimation of Escherichia coli to high temperature over a few
generations of a fed-batch culture during slow warming.
AB - This study aimed to demonstrate that adequate slow heating rate allows two
strains of Escherichia coli rapid acclimation to higher temperature than upper
growth and survival limits known to be strain-dependent. A laboratory (K12-TG1)
and an environmental (DPD3084) strain of E. coli were subjected to rapid (few
seconds) or slow warming (1 degrees C 12 h(-1)) in order to (re)evaluate upper
survival and growth limits. The slow warming was applied from the ancestral
temperature 37 degrees C to total cell death 46-54 degrees C: about 30
generations were propagated. Upper survival and growth limits for rapid warming
(46 degrees C) were lower than for slow warming (46-54 degrees C). The thermal
limit of survival for slow warming was higher for DPD3084 (50-54 degrees C).
Further experiments conducted on DPD3084, showed that mechanisms involved in this
type of thermotolerance were abolished by a following cooling step to 37 degrees
C, which allowed to imply reversible mechanisms as acclimation ones. Acquisition
of acclimation mechanisms was related to physical properties of the plasma
membrane but was not inhibited by unavoidable appearance of aggregated proteins.
In conclusion, E.coli could be rapidly acclimated within few generations over
thermal limits described in the literature. Such a study led us to propose that
rapid acclimation may give supplementary time to the species to acquire a stable
adaptation through a random mutation.
PMID- 24357620
TI - Genetic regulation of flowering time in annual and perennial plants.
AB - Flowering time plays a significant role in the reproductive success of plants. So
far, five major pathways to flowering have been characterized in Arabidopsis,
including environmental induction through photoperiod, vernalization, and
gibberellins and autonomous floral iation, and aging by sequentially operating
miRNAs (typically miR156 and miR172) responding to endogenous cues. The balance
of signals from these pathways is integrated by a common set of genes (FLOWERING
LOCUS C, FLOWERING LOCUS T, LEAFY, and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS
1) that determine the flowering time. Recent studies have indicated that
epigenetic modification, alternative splicing, antisense RNA and chromatin
silencing regulatory mechanisms play an important role in this process by
regulating related flowering gene expression. In this review, we discuss the
current understanding in genetic regulation of the phase transition from
vegetative to reproductive growth by using Arabidopsis as a model. We also
describe how this knowledge has been successfully applied for identifying
homologous genes from perennial crops. Furthermore, detailed analysis of the
similarities and differences between annual and perennial plants flowering will
help elucidate the mechanisms of perennial plant maturation and regulation of
floral initiation.
PMID- 24357619
TI - PIAS1 SUMO ligase regulates the self-renewal and differentiation of hematopoietic
stem cells.
AB - The selective and temporal DNA methylation plays an important role in the self
renewal and differentiation of hematopoietic stem cells (HSCs), but the molecular
mechanism that controls the dynamics of DNA methylation is not understood. Here,
we report that the PIAS1 epigenetic pathway plays an important role in regulating
HSC self-renewal and differentiation. PIAS1 is required for maintaining the
quiescence of dormant HSCs and the long-term repopulating capacity of HSC. Pias1
disruption caused the abnormal expression of lineage-associated genes. Bisulfite
sequencing analysis revealed the premature promoter demethylation of Gata1, a key
myeloerythroid transcription factor and a PIAS1-target gene, in Pias1(-/-) HSCs.
As a result, Pias1 disruption caused the inappropriate induction of Gata1 in HSCs
and common lymphoid progenitors (CLPs). The expression of other myeloerythroid
genes was also enhanced in CLPs and lineage-negative progenitors, with a
concurrent repression of B cell-specific genes. Consistently, Pias1 disruption
caused enhanced myeloerythroid, but reduced B lymphoid lineage differentiation.
These results identify a novel role of PIAS1 in maintaining the quiescence of
dormant HSCs and in the epigenetic repression of the myeloerythroid program.
PMID- 24357621
TI - Association among depressive disorder, adjustment disorder, sleep disturbance,
and suicidal ideation in Taiwanese adolescent.
AB - INTRODUCTION: The aim of this study is to investigate the association among
depressive disorder, adjustment disorder, sleep disturbance, and suicidal
ideation in Taiwanese adolescent. METHODS: We recruited 607 students (grades 5-9)
to fill out the investigation of basic data and sleep disturbance. Psychiatrists
then used the Mini International Neuropsychiatric Interview-Kid to interview
these students to assess their suicidal ideation and psychiatric diagnosis.
Multiple logistic regression with forward conditionals was used to find the risk
factors for multivariate analysis. RESULTS: Female, age, depressive disorder,
adjustment disorder, and poor sleep all contributed to adolescent suicidal
ideation in univariate analysis. However, poor sleep became non-significant under
the control of depressive disorder and adjustment disorder. DISCUSSION: We found
that both depressive disorder and adjustment disorder play important roles in
sleep and adolescent suicidal ideation. After controlling both depressive
disorder and adjustment disorder, sleep disturbance was no longer a risk of
adolescent suicidal ideation. We also confirm the indirect influence of sleep on
suicidal ideation in adolescent.
PMID- 24357622
TI - Disassembly of the cystovirus phi6 envelope by montmorillonite clay.
AB - Prior studies of clay-virus interactions have focused on the stability and
infectivity of nonenveloped viruses, yielding contradictory results. We
hypothesize that the surface charge distribution of the clay and virus envelope
dictates how the components react and affect aggregation, viral stability, and
infectivity. The bacteriophage Cystoviridae species phi6 used in this study is a
good model for enveloped pathogens. The interaction between phi6 and
montmorillonite (MMT) clay (the primary component of bentonite) is explored by
transmission electron microscopy. The analyses show that MMT-phi6 mixtures
undergo heteroaggregation, forming structures in which virtually all the virions
are either sequestered between MMT platelet layers or attached to platelet edges.
The virions swell and undergo disassembly resulting in partial or total envelope
loss. Edge-attached viral envelopes distort to increase contact area with the
positively charged platelet edges indicating that the virion surface is
negatively charged. The nucleocapsid (NCs) remaining after envelope removal also
exhibit distortion, in contrast to detergent-produced NCs which exhibit no
distortion. This visually discernible disassembly is a mechanism for loss of
infectivity previously unreported by studies of nonenveloped viruses. The MMT
mediated sequestration and disassembly result in reduced infectivity, suggesting
that clays may reduce infectivity of enveloped pathogenic viruses in soils and
sediments.
PMID- 24357623
TI - Communicating mega-projects in the face of uncertainties: Israeli mass media
treatment of the Dead Sea Water Canal.
AB - Given the potential for uncertainties to influence mega-projects, this study
examines how mega-projects are deliberated in the public arena. The paper traces
the strategies used to promote the Dead Sea Water Canal. Findings show that the
Dead Sea mega-project was encumbered by ample uncertainties. Treatment of
uncertainties in early coverage was dominated by economics and raised primarily
by politicians, while more contemporary media discourses have been dominated by
ecological uncertainties voiced by environmental non-governmental organizations.
This change in uncertainty type is explained by the changing nature of the
project and by shifts in societal values over time. The study also reveals that
'uncertainty reduction' and to a lesser degree, 'project cancellation', are still
the strategies most often used to address uncertainties. Statistical analysis
indicates that although uncertainties and strategies are significantly
correlated, there may be other intervening variables that affect this
correlation. This research also therefore contributes to wider and ongoing
considerations of uncertainty in the public arena through various media
representational practices.
PMID- 24357625
TI - Fluorescent biosensors for high throughput screening of protein kinase
inhibitors.
AB - High throughput screening assays aim to identify small molecules that interfere
with protein function, activity, or conformation, which can serve as effective
tools for chemical biology studies of targets involved in physiological processes
or pathways of interest or disease models, as well as templates for development
of therapeutics in medicinal chemistry. Fluorescent biosensors constitute
attractive and powerful tools for drug discovery programs, from high throughput
screening assays, to postscreen characterization of hits, optimization of lead
compounds, and preclinical evaluation of candidate drugs. They provide a means of
screening for inhibitors that selectively target enzymatic activity,
conformation, and/or function in vitro. Moreover, fluorescent biosensors
constitute useful tools for cell- and image-based, multiplex and multiparametric,
high-content screening. Application of fluorescence-based sensors to screen large
and complex libraries of compounds in vitro, in cell-based formats or whole
organisms requires several levels of optimization to establish robust and
reproducible assays. In this review, we describe the different fluorescent
biosensor technologies which have been applied to high throughput screens, and
discuss the prerequisite criteria underlying their successful application.
Special emphasis is placed on protein kinase biosensors, since these enzymes
constitute one of the most important classes of therapeutic targets in drug
discovery.
PMID- 24357626
TI - Entering the second year of the transatlantic Andrology collaboration.
PMID- 24357624
TI - Physiologically relevant organs on chips.
AB - Recent advances in integrating microengineering and tissue engineering have
generated promising microengineered physiological models for experimental
medicine and pharmaceutical research. Here we review the recent development of
microengineered physiological systems, or also known as "ogans-on-chips", that
reconstitute the physiologically critical features of specific human tissues and
organs and their interactions. This technology uses microengineering approaches
to construct organ-specific microenvironments, reconstituting tissue structures,
tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical
stimuli found in specific organs, to direct cells to assemble into functional
tissues. We first discuss microengineering approaches to reproduce the key
elements of physiologically important, dynamic mechanical microenvironments,
biochemical microenvironments, and microarchitectures of specific tissues and
organs in microfluidic cell culture systems. This is followed by examples of
microengineered individual organ models that incorporate the key elements of
physiological microenvironments into single microfluidic cell culture systems to
reproduce organ-level functions. Finally, microengineered multiple organ systems
that simulate multiple organ interactions to better represent human physiology,
including human responses to drugs, is covered in this review. This emerging
organs-on-chips technology has the potential to become an alternative to 2D and
3D cell culture and animal models for experimental medicine, human disease
modeling, drug development, and toxicology.
PMID- 24357627
TI - Lessons Learned in Andrology: seeing is believing.
PMID- 24357629
TI - Posttreatment changes in cytokines induced by Schistosoma mansoni egg and worm
antigens: dissociation of immunity- and morbidity-associated type 2 responses.
AB - BACKGROUND: Human type 2 cytokine responsiveness to schistosome antigens
increases after treatment; due either to removal of the immunosuppressive effects
of active infection or immunological boosting by antigens released from dying
parasites. We determined the responsiveness to Schistosoma mansoni over a 2-year
period, when reinfection was restricted by interrupting transmission. METHODS:
The proinflammatory and type 2 responses of Kenyan schoolchildren were measured
before, and 1 year and 2 years posttreatment in whole blood cultures stimulated
with soluble egg antigen (SEA) or soluble worm antigen (SWA). The site of S.
mansoni transmission was molluscicided throughout. RESULTS: Pretreatment
proinflammatory responses to SEA were high but reduced 1 and 2 years
posttreatment, whereas type 2 responses were low pretreatment and increased 1 and
2 years posttreatment. Type 2 responses to SWA were high pretreatment and
increased at 1 year, with no further increases at 2 years posttreatment. Children
infected at follow-up had lower SEA, but not SWA, posttreatment type 2
responsiveness. Increases at 1 year in type 2 SWA, but not SEA, responsiveness
correlated with pretreatment egg counts. CONCLUSIONS: Removal of
immunosuppressive effects of active infection increases SEA type 2
responsiveness; long-term SWA type 2 responsiveness is due to treatment-induced
immunological boosting. Dissociation of type 2 responses potentially protects
against severe egg-associated immunopathology during infection, while allowing
worm-antigen derived immunity to develop.
PMID- 24357628
TI - EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal
microdeletions: state-of-the-art 2013.
AB - The molecular diagnosis of Y-chromosomal microdeletions is a common routine
genetic test which is part of the diagnostic workup of azoospermic and severe
oligozoospermic men. Since 1999, the European Academy of Andrology (EAA) and the
European Molecular Genetics Quality Network (EMQN) have been actively involved in
supporting the improvement of the quality of the diagnostic assays by publication
of the laboratory guidelines for molecular diagnosis of Y-chromosomal
microdeletions and by offering external quality assessment trials. The present
revision of the 2004 laboratory guidelines summarizes all the clinical novelties
related to the Y chromosome (classic, partial and gene-specific deletions,
genotype-phenotype correlations, methodological issues) and provides an update on
the results of the quality control programme. These aspects also reflect the
consensus of a large group of specialists present at a round table session during
the recent Florence-Utah-Symposium on 'Genetics of male infertility' (Florence,
19-21 September, 2013). During the last 10 years the gr/gr deletion has been
demonstrated as a significant risk factor for impaired sperm production. However,
the screening for this deletion type in the routine diagnostic setting is still a
debated issue among experts. The original basic protocol based on two multiplex
polymerase chain reactions remains fully valid and appropriate for accurate
diagnosis of complete AZF deletions and it requires only a minor modification in
populations with a specific Y chromosome background. However, in light of novel
data on genotype-phenotype correlations, the extension analysis for the AZFa and
AZFb deletions is now routinely recommended. Novel methods and kits with
excessively high number of markers do not improve the sensitivity of the test,
may even complicate the interpretation of the results and are not recommended.
Annual participation in an external quality control programme is strongly
encouraged. The 12-year experience with the EMQN/EAA scheme has shown a steep
decline in diagnostic (genotyping) error rate and a simultaneous improvement on
reporting practice.
PMID- 24357631
TI - Vaccination against Staphylococcus aureus pneumonia.
AB - BACKGROUND: Staphylococcus aureus causes serious infections in both hospital and
community settings. Attempts have been made to prevent human infection through
vaccination against bacterial cell-surface antigens; thus far all have failed.
Here we show that superantigens and cytolysins, when used in vaccine cocktails,
provide protection from S. aureus USA100-USA400 intrapulmonary challenge.
METHODS: Rabbits were actively vaccinated (wild-type toxins or toxoids) or
passively immunized (hyperimmune serum) against combinations of superantigens
(toxic shock syndrome toxin 1, enterotoxins B and C, and enterotoxin-like X) and
cytolysins (alpha-, beta-, and gamma-toxins) and challenged intrapulmonarily with
multiple strains of S. aureus, both methicillin-sensitive and methicillin
resistant. RESULTS: Active vaccination against a cocktail containing bacterial
cell-surface antigens enhanced disease severity as tested by infective
endocarditis. Active vaccination against secreted superantigens and cytolysins
resulted in protection of 86 of 88 rabbits when challenged intrapulmonarily with
9 different S. aureus strains, compared to only 1 of 88 nonvaccinated animals.
Passive immunization studies demonstrated that production of neutralizing
antibodies was an important mechanism of protection. CONCLUSIONS: The data
suggest that vaccination against bacterial cell-surface antigens increases
disease severity, but vaccination against secreted virulence factors provides
protection against S. aureus. These results advance our understanding of S.
aureus pathogenesis and have important implications in disease prevention.
PMID- 24357632
TI - HIV "elite controllers" are characterized by a high frequency of memory CD8+
CD73+ T cells involved in the antigen-specific CD8+ T-cell response.
AB - Human immunodeficiency virus type 1 (HIV-1) infection is characterized by chronic
immune activation and suppressed T-lymphocyte functions. Here we report that
CD73, both a coactivator molecule of T cells and an immunosuppressive ecto-enzyme
through adenosine production, is only weakly expressed by CD8+ T cells of HIV
infected patients and only partially restored after successful antiviral
treatment. CD73 expression on CD8+ T cells correlates inversely with cell
activation both ex vivo and in vitro. However, CD8+ T cells from HIV controllers
(HICs), which spontaneously control HIV replication, express CD73 strongly,
despite residual immune activation. Finally, we demonstrate that CD73 is involved
in the HIV-specific CD8+ T-cell expansion. Thus, we show that CD73 is central to
the functionality of HIV-specific CD8+ T cells and that the preservation of HIV
specific CD73+ CD8+ T cells is a characteristic of HICs. These observations
reveal a novel mechanism involved in the control of viral replication.
PMID- 24357630
TI - Protection against epithelial damage during Candida albicans infection is
mediated by PI3K/Akt and mammalian target of rapamycin signaling.
AB - BACKGROUND: The ability of epithelial cells (ECs) to discriminate between
commensal and pathogenic microbes is essential for healthy living. Key to these
interactions are mucosal epithelial responses to pathogen-induced damage.
METHODS: Using reconstituted oral epithelium, we assessed epithelial gene
transcriptional responses to Candida albicans infection by microarray. Signal
pathway activation was monitored by Western blotting and transcription factor
enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans
induced damage protection was determined using chemical inhibitors. RESULTS:
Transcript profiling demonstrated early upregulation of epithelial genes involved
in immune responses. Many of these genes constituted components of signaling
pathways, but only NF-kappaB, MAPK, and PI3K/Akt pathways were functionally
activated. We demonstrate that PI3K/Akt signaling is independent of NF-kappaB and
MAPK signaling and plays a key role in epithelial immune activation and damage
protection via mammalian target of rapamycin (mTOR) activation. CONCLUSIONS:
PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells
from damage during mucosal fungal infections independent of NF-kappaB or MAPK
signaling.
PMID- 24357633
TI - Newly engineered cyan fluorescent proteins with enhanced performances for live
cell FRET imaging.
AB - Cyan fluorescent proteins (CFPs) derived from Aequorea victoria green fluorescent
protein are the most widely used Forster resonant energy transfer (FRET) donors
in genetically encoded biosensors for live-cell imaging and bioassays. However,
the weak and complex fluorescence emission of cyan variants, such as enhanced
cyan fluorescent protein (ECFP) or Cerulean, has long remained a major bottleneck
in these FRET techniques. Recently, several CFPs with greatly improved
performances, including mTurquoise, mTurquoise2, mCerulean3, and Aquamarine, have
been engineered through a mixture of site-directed and large-scale random
mutagenesis. This review summarizes the engineering and relative merits of these
new cyan donors, which can readily replace popular CFPs in FRET imaging
protocols, while reaching fluorescence quantum yields close to 90%, and
unprecedented long, near-single fluorescence lifetimes of about 4 ns. These
variants display an increased general photostability and much reduced
environmental sensitivity, notably towards acid pH. These new, bright, and robust
CFPs now open up exciting outlooks for fluorescence lifetime imaging microscopy
and advanced quantitative FRET analyses in living cells. In addition, the
stepwise engineering of Aquamarine shows that only two critical mutations in
ECFP, and one in Cerulean, are required to achieve these performances, which
brings new insights into the structural bases of their photophysical properties.
PMID- 24357635
TI - Proper hepatic artery reconstruction with gastroduodenal artery transposition
during pancreaticoduodenectomy.
AB - INTRODUCTION: Vascular injuries to hepatic arterial blood flow present a
challenge in reconstruction. The location and extent of the injury dictate
intraoperative decision making, with repair being performed expeditiously to
preserve hepatic function. Formal arterial repair either primarily or with
interposition or transposition grafts is indicated in the majority of patients.
Special consideration should be made in patients with underlying liver disease
and those undergoing biliary reconstructions. This latter group of patients is at
high risk of complications following the injury secondary to bile duct ischemia.
METHODS: A case of proper hepatic artery (PHA) transection repaired with
gastroduodenal artery (GDA) transposition is presented with a relevant review of
limited literature available on the subject. RESULTS: During an elective
pancreaticoduodenectomy the PHA was inadvertently transected just distal to the
origin of the GDA. As the GDA had not been transected at this stage of the
operation, it was available for transposition. This was performed, restoring
arterial blood flow to the liver and the bile duct. The patient did well
postoperatively with no evidence of biliary or pancreatic leak or hepatic
dysfunction at both discharge and follow-up clinic visit. CONCLUSION: Injuries to
hepatic artery injury are uncommon in experienced hands. This case report is only
the second instance of such injury requiring reconstruction in 434 cases of
single operator experience pancreaticoduodenectomies. We present arterial
transposition of GDA as a feasible method to ensure adequate arterial supply to
the hepatobiliary system.
PMID- 24357634
TI - The mechanism of translation initiation on Type 1 picornavirus IRESs.
AB - Picornavirus Type 1 IRESs comprise five principal domains (dII-dVI). Whereas dV
binds eIF4G, a conserved AUG in dVI was suggested to stimulate attachment of 43S
ribosomal preinitiation complexes, which then scan to the initiation codon.
Initiation on Type 1 IRESs also requires IRES trans-acting factors (ITAFs), and
several candidates have been proposed. Here, we report the in vitro
reconstitution of initiation on three Type 1 IRESs: poliovirus (PV), enterovirus
71 (EV71), and bovine enterovirus (BEV). All of them require eIF2, eIF3, eIF4A,
eIF4G, eIF4B, eIF1A, and a single ITAF, poly(C) binding protein 2 (PCBP2). In
each instance, initiation starts with binding of eIF4G/eIF4A. Subsequent
recruitment of 43S complexes strictly requires direct interaction of their eIF3
constituent with eIF4G. The following events can differ between IRESs, depending
on the stability of dVI. If it is unstructured (BEV), all ribosomes scan through
dVI to the initiation codon, requiring eIF1 to bypass its AUG. If it is
structured (PV, EV71), most initiation events occur without inspection of dVI,
implying that its AUG does not determine ribosomal attachment.
PMID- 24357636
TI - History of carotid surgery: from ancient greeks to the modern era.
AB - A relationship between decreased carotid arterial flow and apoplectic
manifestations was already suspected by the ancient Greeks. Early attempts at
carotid surgery, however, were limited to emergency arterial ligation in patients
with neck trauma. Attempts to suture arterial stumps together to restore blood
flow paved the way for Carrel's revolutionary idea of reconstructing the resected
or injured arterial segment with an interposition vein graft. DeBakey and
Eastcott were the first to perform carotid endarterectomy in North America and
the United Kingdom, respectively. In 1959, DeBakey proposed a cooperative study
to assess the effectiveness of carotid endarterectomy in the treatment and
prevention of ischemic cerebrovascular disease. The study was officially
designated the Joint Study of Extracranial Arterial Occlusion and represented the
first trial in the United States in which large numbers of patients were randomly
allocated to surgical or nonsurgical therapy.
PMID- 24357637
TI - Cellular evidence for selfish spermatogonial selection in aged human testes.
AB - Owing to a recent trend for delayed paternity, the genomic integrity of
spermatozoa of older men has become a focus of increased interest. Older fathers
are at higher risk for their children to be born with several monogenic
conditions collectively termed paternal age effect (PAE) disorders, which include
achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused
by specific mutations originating almost exclusively from the male germline, in
genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling
pathway. These particular mutations, occurring randomly during mitotic divisions
of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth
advantage on the mutant SSC. This selective advantage leads to a clonal expansion
of the mutant cells over time, which generates mutant spermatozoa at levels
significantly above the background mutation rate. This phenomenon, termed selfish
spermatogonial selection, is likely to occur in all men. In rare cases, probably
because of additional mutational events, selfish spermatogonial selection may
lead to spermatocytic seminoma. The studies that initially predicted the clonal
nature of selfish spermatogonial selection were based on DNA analysis, rather
than the visualization of mutant clones in intact testes. In a recent study that
aimed to identify these clones directly, we stained serial sections of fixed
testes for expression of melanoma antigen family A4 (MAGEA4), a marker of
spermatogonia. A subset of seminiferous tubules with an appearance and
distribution compatible with the predicted mutant clones were identified. In
these tubules, termed 'immunopositive tubules', there is an increased density of
spermatogonia positive for markers related to selfish selection (FGFR3) and SSC
self-renewal (phosphorylated AKT). Here we detail the properties of the
immunopositive tubules and how they relate to the predicted mutant clones, as
well as discussing the utility of identifying the potential cellular source of
PAE mutations.
PMID- 24357638
TI - Toxic effects of maternal zearalenone exposure on uterine capacity and fetal
development in gestation rats.
AB - The objectives of this study were to determine the effects of high-dose and early
gestational exposure to zearalenone (ZEN) in female Sprague-Dawley (SD) rats, to
correlate the maternal uterus with the fetus, and to explore the development and
malformation of fetuses. Pregnant female SD rats were fed diets containing 0.3,
48.5, 97.6, or 146.0 mg/kg ZEN on gestational days (GDs) 0 through 7. All the
females survived until GD 20, at which point a cesarean section was performed to
harvest the organs, blood, and fetuses. The results indicated that exposure to
ZEN during early gestation can impact the maternal reproductive capability.
Delayed fetal development was directly linked to maternal toxicity. The toxic
effects of ZEN caused early deaths more frequently than late deaths, and the
deleterious effects lasted through the end of pregnancy.
PMID- 24357639
TI - Prevalence of male pelvic dysfunction: results from the Turkish society of
andrology male sexual health study group.
AB - The objective of this study was to determine the prevalence of male pelvic
dysfunction (MPD) and its correlation in men >=40 years of age in a population
based study. This study was designed as a non-interventional, observational,
cross-sectional field survey. Participating males of >=40 years were randomly
selected from 19 provinces of Turkey. All participants were asked to complete a
survey including data regarding demographics, socio-economic status, socio
cultural factors, medical and sexual history, current medications, comorbidities
and three validated questionnaires assessing lower urinary tract symptoms
(International Prostate Symptom Score), erectile dysfunction (International Index
of Erectile Function) and ejaculatory behaviour (Male Sexual Health Questionnaire
4). MPD was defined by combining abnormal scores calculated from all three
questionnaires. All data were analysed statistically and p < 0.05 was accepted as
significant. A total of 2730 males of >=40 years (mean, 54.2 +/- 10.6 years) were
enrolled in this study. The prevalence of MPD was calculated as 24.4% among all
participants. The prevalence of MPD was lowest at age between 40 and 49 years
(9.1%) and highest at >=70 years (76.6%), exhibiting correlation with age. Each
decade of increase in age was associated with a 3.4-fold increase in presence of
MPD. At logistic regression analyses; age, diabetes, hypertension, dyslipidemia,
cardiovascular disease, obesity and lower income were found to be independent
predictors for increased prevalence of MPD. This study reports prevalence of MPD
as 24.4% in males of >=40 years. Furthermore, age was found to be the main
independent predictor of having MPD.
PMID- 24357641
TI - Right ventricular adaptations and arrhythmias in amateur ultra-endurance
athletes.
AB - OBJECTIVE: Ultra-endurance sports are becoming increasingly popular in middle
aged amateur athletes. Right ventricular (RV) arrhythmogenic remodelling has been
described in high-level endurance athletes, like professional cyclists. The
clinical relevance for amateurs is unknown. DESIGN: We investigated male amateur
runners of the 2011 Grand Prix of Bern, a popular 10-mile race in Switzerland.
Participants were stratified according to their former participations in long
distance competitions: active controls (leisure-time runners), marathon runners
and ultra-endurance athletes (78 and 100 km runners, long-distance triathletes).
RV function and morphology were assessed by echocardiography, including two
dimensional speckle tracking. Primary endpoint was RV global strain. Ventricular
ectopy was assessed by 24 h ambulatory Holter monitoring. Results were adjusted
for lifetime training hours. RESULTS: 97 normotensive athletes were included in
the final analysis. The mean age was 42+/-8 years. Compared with active controls
and marathon runners, ultra-endurance athletes had significantly more lifetime
training hours and participated more often in competitions. Groups showed no
differences with regard to RV global strain (-21.8+/-2.9 vs -23.3+/-2.8 vs
21.7+/-2.3%; p=0.973) and RV end-diastolic area (22.1+/-2.9 vs 22.9+/-4.2 vs
23.2+/-3.5 cm(2); p=0.694). The number of premature ventricular contractions
(PVCs) was weakly associated with the RV size (r=0.208; p=0.042). Overall
ventricular ectopy was low (0-486 PVCs/24 h) and equally distributed between the
groups. CONCLUSIONS: In our small sample of amateur athletes, long-term ultra
endurance sport practice was not associated with RV dysfunction or complex
ventricular arrhythmias.
PMID- 24357642
TI - Examining injury risk and pain perception in runners using minimalist footwear.
AB - BACKGROUND: This study examines the effect of progressive increases in footwear
minimalism on injury incidence and pain perception in recreational runners.
METHODS: One hundred and three runners with neutral or mild pronation were
randomly assigned a neutral (Nike Pegasus 28), partial minimalist (Nike Free 3.0
V2) or full minimalist shoe (Vibram 5-Finger Bikila). Runners underwent baseline
testing to record training and injury history, as well as selected anthropometric
measurements, before starting a 12-week training programme in preparation for a
10 km event. Outcome measures included number of injury events, Foot and Ankle
Disability (FADI) scores and visual analogue scale pain rating scales for
regional and overall pain with running. RESULTS: 99 runners were included in
final analysis with 23 injuries reported; the neutral shoe reporting the fewest
injuries (4) and the partial minimalist shoe (12) the most. The partial
minimalist shoe reported a significantly higher rate of injury incidence
throughout the 12-week period. Runners in the full minimalist group reported
greater shin and calf pain. CONCLUSIONS: Running in minimalist footwear appears
to increase the likelihood of experiencing an injury, with full minimalist
designs specifically increasing pain at the shin and calf. Clinicians should
exercise caution when recommending minimalist footwear to runners otherwise new
to this footwear category who are preparing for a 10 km event.
PMID- 24357640
TI - Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast.
AB - Mammary epithelial stem cells are fundamental to maintain tissue integrity.
Cancer stem cells (CSCs) are implicated in both treatment resistance and disease
relapse, and the molecular bases of their malignant properties are still poorly
understood. Here we show that both normal stem cells and CSCs of the breast are
controlled by the prolyl-isomerase Pin1. Mechanistically, following interaction
with Pin1, Notch1 and Notch4, key regulators of cell fate, escape from
proteasomal degradation by their major ubiquitin-ligase Fbxw7alpha. Functionally,
we show that Fbxw7alpha acts as an essential negative regulator of breast CSCs'
expansion by restraining Notch activity, but the establishment of a Notch/Pin1
active circuitry opposes this effect, thus promoting breast CSCs self-renewal,
tumor growth and metastasis in vivo. In human breast cancers, despite Fbxw7alpha
expression, high levels of Pin1 sustain Notch signaling, which correlates with
poor prognosis. Suppression of Pin1 holds promise in reverting aggressive
phenotypes, through CSC exhaustion as well as recovered drug sensitivity carrying
relevant implications for therapy of breast cancers.
PMID- 24357643
TI - Regulatory forum opinion piece: Clarification and simplification of the pathology
peer review documentation process.
AB - The transparency and documentation of the peer review process have been discussed
recently. Our position is that transparency is best achieved when peer review is
a collaborative process, in which both parties are open-minded but both also
realize that the study pathologist retains complete control over the findings
(raw data) and over the content of the pathology report. For these reasons, we
believe that histopathology raw data should be defined as the observations made
by the study pathologist (printed and/or electronic formats) rather than as the
tissue slides recommended by the Organisation for Economic Co-operation and
Development (OECD). Also, because the study pathologist retains control over the
histopathology raw data, any notes or tabulations of findings by the study
pathologist and peer review pathologist during the peer review are interim notes
and should not be included as an appendix to the pathology report though they may
be retained if desired, as currently recommended. Because the histopathology raw
data have not been created until completion of the peer review, the performance
of a peer review should be documented in the study report, as currently
recommended, but that it not be a GLP-compliant process.
PMID- 24357644
TI - Regulatory forum opinion piece: Peer review documentation and pathology data
locking.
PMID- 24357645
TI - Adipose- and bone marrow-derived mesenchymal stem cells display different
osteogenic differentiation patterns in 3D bioactive glass-based scaffolds.
AB - Mesenchymal stem cells can be isolated from a variety of different sources, each
having their own peculiar merits and drawbacks. Although a number of studies have
been conducted comparing these stem cells for their osteo-differentiation
ability, these are mostly done in culture plastics. We have selected stem cells
from either adipose tissue (ADSCs) or bone marrow (BMSCs) and studied their
differentiation ability in highly porous three-dimensional (3D) 45S5 Bioglass(r)
based scaffolds. Equal numbers of cells were seeded onto 5 * 5 * 4 mm3 scaffolds
and cultured in vitro, with or without osteo-induction medium. After 2 and 4
weeks, the cell-scaffold constructs were analysed for cell number, cell
spreading, viability, alkaline phosphatase activity and osteogenic gene
expression. The scaffolds with ADSCs displayed osteo-differentiation even without
osteo-induction medium; however, with osteo-induction medium osteogenic
differentiation was further increased. In contrast, the scaffolds with BMSCs
showed no osteo-differentiation without osteo-induction medium; after application
of osteo-induction medium, osteo-differentiation was confirmed, although lower
than in scaffolds with ADSCs. In general, stem cells in 3D bioactive glass
scaffolds differentiated better than cells in culture plastics with respect to
their ALP content and osteogenic gene expression. In summary, 45S5 Bioglass-based
scaffolds seeded with ADSCs are well-suited for possible bone tissue-engineering
applications. Induction of osteogenic differentiation appears unnecessary prior
to implantation in this specific setting. Copyright (c) 2013 John Wiley & Sons,
Ltd.
PMID- 24357646
TI - Insulin sensitivity and brain reward activation in overweight Hispanic girls: a
pilot study.
AB - BACKGROUND: Insulin resistance is a link between obesity and the associated
disease risk. In addition to its role as an energy regulatory signal to the
hypothalamus, insulin also modulates food reward. OBJECTIVE: To examine the
relationship of insulin sensitivity (SI) and fasting insulin with cerebral
activation in response to food and non-food cues in children. METHODS: Twelve
overweight Hispanic girls (age: 8-11) participated in two study visits, a
frequently sampled intravenous glucose tolerance test and a functional
neuroimaging session (GE HDxt 3.0Tesla) with visual stimulation tasks. Blocks of
images (high calorie [HC], low calorie [LC] and non-food [NF]) were presented in
randomized order. RESULTS: Comparing HC with NF, SI was inversely associated with
activation in the anterior cingulate (r(2) = 0.65; P < 0.05), the insula (r(2)
= 0.69; P < 0.05), the orbitofrontal cortex (r(2) = 0.74; P < 0.05), and the
frontal and rolandic operculum (r(2) = 0.76; P < 0.001). Associations remained
significant after adjustment for body mass index. Association of fasting insulin
and cerebral activation disappeared after adjustment for waist circumference.
CONCLUSION: In addition to weight loss, insulin sensitivity may pose an important
target to regulate neural responses to food cues in the prevention of excessive
weight gain.
PMID- 24357647
TI - Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes
survival in sepsis.
AB - Incorporation of locally produced signaling molecules into cell-derived vesicles
may serve as an endogenous mediator delivery system. We recently reported that
levels alpha-2-macroglobulin (A2MG)-containing microparticles are elevated in
plasma from patients with sepsis. Herein, we investigated the immunomodulatory
actions of A2MG containing microparticles during sepsis. Administration of A2MG
enriched (A2MG-E)-microparticles to mice with microbial sepsis protected against
hypothermia, reduced bacterial titers, elevated immunoresolvent lipid mediator
levels in inflammatory exudates and reduced systemic inflammation. A2MG-E
microparticles also enhanced survival in murine sepsis, an action lost in mice
transfected with siRNA for LRP1, a putative A2MG receptor. In vitro, A2MG was
functionally transferred onto endothelial cell plasma membranes from
microparticles, augmenting neutrophil-endothelial adhesion. A2MG also modulated
human leukocyte responses: enhanced bacterial phagocytosis, reactive oxygen
species production, cathelicidin release, prevented endotoxin induced CXCR2
downregulation and preserved neutrophil chemotaxis in the presence of LPS. A
significant association was also found between elevated plasma levels of A2MG
containing microparticles and survival in human sepsis patients. Taken together,
these results identify A2MG enrichment in microparticles as an important host
protective mechanism in sepsis.
PMID- 24357649
TI - Pesticides and bees.
PMID- 24357648
TI - Self-management as a mediator of family functioning and depressive symptoms with
health outcomes in youth with type 1 diabetes.
AB - This study examined the relationship of family functioning and depressive
symptoms with self-management, glycemic control, and quality of life in a sample
of adolescents with type 1 diabetes. It also explored whether self-management
mediates family functioning, depressive symptoms, and diabetes-related outcomes.
Structural equation modeling was used to estimate parameters in the conceptual
causal pathway and test mediation effects. Adolescents (n = 320) were primarily
female (55%), younger adolescents (58%), and self-identified as White (63%). Self
management mediated the relationship between family conflict, family warmth
caring, parent guidance-control, and youth depressive symptoms with glycosylated
hemoglobin (A1C). In addition, self-management mediated the relationship between
family conflict and youth depressive symptoms with quality of life. Supporting
optimal family functioning and treating elevated depressive symptoms in
adolescents with type 1 diabetes has the potential to improve self-management,
glycemic control, and quality of life.
PMID- 24357651
TI - Walking with the IHS on basic mechanisms in headache research.
PMID- 24357652
TI - Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and
mitophagy.
AB - PINK1 is a mitochondrial kinase proposed to have a role in the pathogenesis of
Parkinson's disease through the regulation of mitophagy. Here, we show that the
PINK1 main cleavage product, PINK152, after being generated inside mitochondria,
can exit these organelles and localize to the cytosol, where it is not only
destined for degradation by the proteasome but binds to Parkin. The interaction
of cytosolic PINK1 with Parkin represses Parkin translocation to the mitochondria
and subsequent mitophagy. Our work therefore highlights the existence of two
cellular pools of PINK1 that have different effects on Parkin translocation and
mitophagy.
PMID- 24357654
TI - Cerebral venous thrombosis: diagnosis and management.
PMID- 24357653
TI - Education for nurses working in cardiovascular care: a European survey.
AB - BACKGROUND: Nurses represent the largest sector of the workforce caring for
people with cardiovascular disease in Europe. Little is known about the post
registration education provided to nurses working within this specialty. The aim
of this descriptive cross sectional survey was to describe the structure,
content, teaching, learning, assessment and evaluation methods used in post
registration cardiovascular nurse education programmes in Europe. METHOD: A 24
item researcher generated electronic questionnaire was sent to nurse
representatives from 23 European countries. Items included questions about
cardiovascular registered nurse education programmes. RESULTS: Forty-nine
respondents from 17 European countries completed questionnaires. Respondents were
typically female (74%) and educated at Masters (50%) or doctoral (39%) level.
Fifty-one percent of the cardiovascular nursing education programmes were offered
by universities either at bachelor or masters level. The most frequently reported
programme content included cardiac arrhythmias (93%), heart failure (85%) and
ischaemic heart disease (83%). The most common teaching mode was face-to-face
lectures (85%) and/or seminars (77%). A variety of assessment methods were used
with an exam or knowledge test being the most frequent. Programme evaluation was
typically conducted through student feedback (95%). CONCLUSION: There is
variability in the content, teaching, learning and evaluation methods in post
registration cardiovascular nurse education programmes in Europe. Cardiovascular
nurse education would be strengthened with a stronger focus upon content that
reflects current health challenges faced in Europe. A broader view of
cardiovascular disease to include stroke and peripheral vascular disease is
recommended with greater emphasis on prevention, rehabilitation and the impact of
health inequalities.
PMID- 24357655
TI - Carotid bifurcation geometry is an independent predictor of early wall thickening
at the carotid bulb.
AB - BACKGROUND AND PURPOSE: Lumen geometry has long been suspected as a risk factor
for atherosclerosis by virtue of its influence on blood flow disturbances.
Confirmation of this geometric risk hypothesis has, however, proved challenging
owing to possible effects of wall thickening on geometry and unproven links
between candidate geometric variables and disturbed flow. The purpose of this
study was to overcome these challenges. METHODS: The study relied on imaging and
risk factor data from progressively refined subsets of the Atherosclerosis Risk
in Communities (ARIC) Carotid MRI study. Group 1 (n=467) included only
nonstenotic cases having sufficient quality angiography for 3-dimensional
analysis. Group 2 (n=346) excluded cases from group 1 having common and internal
carotid artery wall thickness above previously identified thresholds for inward
remodeling. Group 3 (n=294) excluded cases from group 2 having lumen
irregularities and thus was least likely to include lumen geometries influenced
by wall thickening. RESULTS: Multiple linear regressions showed that for group 3,
bifurcation flare and proximal curvature were independent predictors of internal
carotid artery wall thickness, consistent with their previously demonstrated
roles in predicting disturbed flow. For the broadest group 1, flare was an
independent predictor of internal carotid artery wall thickness but with a sign
change in regression coefficient reflecting effects of wall thickening on lumen
geometry. CONCLUSIONS: Carotid bifurcation geometry is an independent, albeit
weak, predictor of its early wall thickening, but only when assumptions about
geometric factors, and the influence of disease on them, are confronted. This
highlights pitfalls of previous attempts to confirm geometric risk of
atherosclerosis.
PMID- 24357656
TI - Prospective study of anxiety and incident stroke.
AB - BACKGROUND AND PURPOSE: Higher levels of anxiety are associated with increased
risk for coronary heart disease. However, few studies have investigated whether
anxiety is associated with stroke risk. The purpose of this study was to examine
the association between anxiety symptoms and incident stroke in a nationally
representative longitudinal study of the US population. METHODS: Participants
(n=6019) in the First National Health and Nutrition Examination Survey were
assessed at baseline and followed for 16.29+/-4.75 years. Multivariate Cox
proportional hazards regression models were used to estimate hazard ratios and
95% confidence intervals of incident stroke associated with a 1 SD increase in
anxiety symptoms. Models were adjusted for standard cardiovascular risk factors
and additionally for depression. RESULTS: A total of 419 incident stroke cases
were identified from hospital/nursing home discharge reports and death
certificates. Reporting more anxiety symptoms at baseline was associated with
increased risk of incident stroke after adjusting for standard biological and
behavioral cardiovascular risk factors (hazard ratio, 1.14; 95% confidence
interval, 1.03-1.25). Findings persisted when additionally controlling for
depression. Exploratory analyses considering the role of potential confounding
versus pathway variables suggested that behavioral factors may be a key pathway
linking anxiety to stroke risk. CONCLUSIONS: Higher anxiety symptom levels were
associated prospectively with increased risk for incident stroke independent of
other risk factors, including depression. Anxiety is a modifiable experience that
is highly prevalent among the general population. Its assessment and treatment
may contribute to developing more effective preventive and intervention
strategies for improving overall cardiovascular health.
PMID- 24357657
TI - Awareness of the role of atrial fibrillation as a cause of ischemic stroke.
PMID- 24357658
TI - Non-ST-elevation myocardial infarction in patients undergoing carotid
endarterectomy or carotid artery stent placement.
AB - BACKGROUND AND PURPOSE: The significance of non-ST-elevation myocardial
infarction (NSTEMI) after carotid endarterectomy or carotid angioplasty and stent
placement is unknown. We performed this study to identify the frequency of NSTEMI
and impact on outcomes related to carotid endarterectomy or carotid artery stent
placement in patients treated in a large national cohort. METHODS: We determined
the frequency of NSTEMI and associated in-hospital outcomes including mortality
and composite of stroke, cardiac events, and mortality using data from the
Nationwide Inpatient Survey from 2002 to 2009. RESULTS: Of 1 083 688 patients who
underwent carotid endarterectomy or carotid artery stent placement, 11 341 (1%)
patients developed NSTEMI during hospitalization. After adjusting for
constitutional variables and risk factors, NSTEMI was associated with higher
rates of in-hospital mortality (odds ratio, 8.6; 95% confidence interval, 7.0
10.7; P<=0.0001) and composite end point of stroke, cardiac events, and death
(odds ratio, 14.6; 95% confidence interval, 13.0-16.5; P<=0.0001). CONCLUSIONS:
Our results contradict the notion that NSTEMI is a relatively benign entity after
carotid endarterectomy or carotid artery stent placement.
PMID- 24357659
TI - Perfusion of ischemic brain in young and aged animals: a laser speckle flowmetry
study.
AB - BACKGROUND AND PURPOSE: Aging is an important determinant of ischemic stroke
outcomes. Both clinical and experimental stroke studies have shown that aging
negatively correlates with infarct volumes but is associated with worsened
functional recovery after stroke. This may correspond to a differing cellular and
molecular response to stroke in the aged versus young brain. It was hypothesized
in this study that the smaller injury seen in the aged ischemic brain is because
of structural differences in microvasculature with aging or differences in
intraischemic tissue perfusion. METHODS: Both young and aged C57BL6 mice were
subject to middle cerebral artery occlusion modeling. Laser speckle flowmetry was
used to study the functional dynamics of cerebral perfusion, and fluorescein
isothiocyanate (FITC)-dextran staining was performed to examine the structural
change in microvasculature. In separate cohorts, cresyl violet staining and
immunohistochemistry with CD31 and IgG antibodies were applied to further assess
the microvascular density and blood-brain barrier breakdown after stroke.
RESULTS: No difference in cerebral blood flow was seen at the baseline,
intraischemically, and postreperfusion in young versus aged mice. FITC-dextran
and CD31 staining did not show significant differences in the microvascular
density between young and aged ischemic brains. More extravasation of IgG through
the blood-brain barrier was found in the young versus aged cohort at both 24 and
72 hours after stroke. CONCLUSIONS: Cerebrovascular dynamics and perfusion are
not responsible for the different stroke phenotypes seen in the young versus aged
animals, which may be more related to different levels of blood-brain barrier
breakdown.
PMID- 24357660
TI - Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta
glutamate receptors.
AB - The orphan GluD2 receptor belongs to the ionotropic glutamate receptor family but
does not bind glutamate. Ligand-gated GluD2 currents have never been evidenced,
and whether GluD2 operates as an ion channel has been a long-standing question.
Here, we show that GluD2 gating is triggered by type 1 metabotropic glutamate
receptors, both in a heterologous expression system and in Purkinje cells. Thus,
GluD2 is not only an adhesion molecule at synapses but also works as a channel.
This gating mechanism reveals new properties of glutamate receptors that emerge
from their interaction and opens unexpected perspectives regarding synaptic
transmission and plasticity.
PMID- 24357661
TI - Spermatogonial stem cells from domestic animals: progress and prospects.
AB - Spermatogenesis, an elaborate and male-specific process in adult testes by which
a number of spermatozoa are produced constantly for male fertility, relies on
spermatogonial stem cells (SSCs). As a sub-population of undifferentiated
spermatogonia, SSCs are capable of both self-renewal (to maintain sufficient
quantities) and differentiation into mature spermatozoa. SSCs are able to convert
to pluripotent stem cells during in vitro culture, thus they could function as
substitutes for human embryonic stem cells without ethical issues. In addition,
this process does not require exogenous transcription factors necessary to
produce induced-pluripotent stem cells from somatic cells. Moreover, combining
genetic engineering with germ cell transplantation would greatly facilitate the
generation of transgenic animals. Since germ cell transplantation into infertile
recipient testes was first established in 1994, in vivo and in vitro study and
manipulation of SSCs in rodent testes have been progressing at a staggering rate.
By contrast, their counterparts in domestic animals, despite the failure to reach
a comparable level, still burgeoned and showed striking advances. This review
outlines the recent progressions of characterization, isolation, in vitro
propagation, and transplantation of spermatogonia/SSCs from domestic animals,
thereby shedding light on future exploration of these cells with high value, as
well as contributing to the development of reproductive technology for large
animals.
PMID- 24357662
TI - Fetal-maternal communication: the role of Notch signalling in embryo
implantation.
AB - The establishment of a successful pregnancy requires the implantation of a
competent blastocyst into a 'receptive' endometrium, facilitating the formation
of a functional placenta. Inadequate or inappropriate implantation and
placentation is a major reason for infertility and is thought to lead to first
trimester miscarriage, placental insufficiency and other obstetric complications.
Blastocyst-endometrial interactions are critical for implantation and placental
formation. The Notch signalling family is a receptor-ligand family that regulates
cellular processes as diverse as proliferation, apoptosis, differentiation,
invasion and adhesion. Notch signalling is achieved via cell-cell interaction;
thus, via Notch, cells can have direct effects on the fate of their neighbours.
Recently, a number of studies have identified Notch receptors and ligands in the
endometrium, blastocyst and placenta. This review collates current knowledge of
this large receptor-ligand family and explores the role of Notch signalling
during implantation and placentation, drawing on information from both human and
animal studies. Overall, the evidence suggests that Notch signalling is a
critical component of fetal-maternal communication during implantation and
placentation and that abnormal Notch expression is associated with impaired
placentation and pre-eclampsia.
PMID- 24357663
TI - Short oestrous cycles in sheep during anoestrus involve defects in progesterone
biosynthesis and luteal neovascularisation.
AB - Anoestrous ewes can be induced to ovulate by the socio-sexual, 'ram effect'.
However, in some ewes, the induced ovulation is followed by an abnormally short
luteal phase causing a so-called 'short cycle'. The defect responsible for this
luteal dysfunction has not been identified. In this study, we investigated
ovarian and uterine factors implicated in male-induced short cycles in anoestrous
ewes using a combined endocrine and molecular strategy. Before ovulation, we were
able to detect a moderate loss of thecal expression of steroid acute regulatory
protein (STAR) in ewes that had not received progesterone priming (which prevents
short cycles). At and following ovulation, we were able to identify a significant
loss of expression of genes coding key proteins involved in the biosynthesis of
progesterone (STAR, CYP11A1 and HSD3B1 (HSD3B)) as well as genes coding proteins
critical for vascular development during early luteal development (VEGFA and KDR
(VEGFR2)), suggesting dysfunction in at least two pathways critical for normal
luteal function. Furthermore, these changes were associated with a significant
reduction of progesterone production and luteal weight. Additionally, we cast
doubt on the proposed uterus-mediated effect of prostaglandin F2alpha (PGF2alpha)
as a cause of short cycles by demonstrating the dysregulation of luteal
expression of the PGF receptor, which mediates the luteal effects of PGF2alpha,
and by finding no significant changes in the circulating concentrations of PGFM,
the principal metabolite of PGF2alpha in ewes with short cycles. This study is
the first of its kind to examine concurrently the endocrine and molecular events
in the follicular and early luteal stages of the short cycle.
PMID- 24357664
TI - Identification of differentially expressed proteins in fresh and frozen-thawed
boar spermatozoa by iTRAQ-coupled 2D LC-MS/MS.
AB - Cryodamage is a major problem in semen cryopreservation, causing changes in the
levels of proteins that influence the function and motility of spermatozoa. In
this study, protein samples prepared from fresh and frozen-thawed boar
spermatozoa were compared using the isobaric tags for relative and absolute
quantification (iTRAQ) labeling technique coupled to 2D LC-MS/MS analysis. A
total of 41 differentially expressed proteins were identified and quantified,
including 35 proteins that were present at higher levels and six proteins that
were present at lower levels in frozen-thawed spermatozoa by at least a mean of
1.79-fold (P<0.05). On classifying into ten distinct categories using
bioinformatic analysis, most of the 41 differentially expressed proteins were
found to be closely relevant to sperm premature capacitation, adhesions, energy
supply, and sperm-oocyte binding and fusion. The expression of four of these
proteins, SOD1, TPI1, ODF2, and AKAP3, was verified by western blot analysis. We
propose that alterations in these identified proteins affect the quality of
cryopreserved semen and ultimately lower its fertilizing capacity. This is the
first study to compare protein levels in fresh and frozen-thawed spermatozoa
using the iTRAQ technology. Our preliminary results provide an overview of the
molecular mechanisms of cryodamage in frozen-thawed spermatozoa and theoretical
guidance to improve the cryopreservation of boar semen.
PMID- 24357665
TI - Adherence reporting in randomized controlled trials.
AB - BACKGROUND: Treatment adherence may influence the therapeutic effect that is
observed in a randomized controlled trial (RCT). Adherence may also be an
indicator of research quality and treatment acceptance by participants. Despite
the importance of adherence in RCT research, little is known about current
practices for its measurement and reporting. PURPOSE: The objective of this study
was to determine and evaluate adherence measurement and reporting practices in
RCTs involving oral pharmacologic interventions published in high impact factor
journals. METHODS: We conducted a systematic review of RCTs involving oral
pharmacotherapy published during 2010 in 10 high-impact general medicine and
subspecialty journals. Two investigators independently abstracted data regarding
trial characteristics, adherence monitoring, and adherence reporting. Differences
were reconciled in conference. Descriptive statistics were calculated,
statistical comparisons were made using chi-square analysis, and associations
assessed using Spearman's rank correlation coefficient. RESULTS: Of 111 RCT
manuscripts included in the sample, 51 (45.9%) reported study-drug adherence
among participants. Studies that reported adherence results were more likely to
report negative findings (i.e., no significant treatment effect in a superiority
trial, non-equivalence in an equivalence trial) (p = 0.032). The most common
method for adherence monitoring was pill count-back on returned bottles. Among
the studies that reported adherence, the median adherence was 88.4% (range: 48%
100%), and trials with longer follow-up time reported lower adherence (r = -0.45;
p = 0.0015). A minority of the 51 studies described a strategy for calculating
adherence that accounted for participants who were lost to follow-up (11/51
studies; 21.6%), discontinued the study medication temporarily (6/51 studies;
11.8%), or discontinued the study drug permanently (1/51 study; 2%). LIMITATIONS:
This study is limited by the inclusion of a small set of journals with the
highest impact factors in specific fields of clinical medicine, including general
medicine. Although the analysis pertains to studies published in 2010, no new
guidelines in the field since the last Consolidated Standards of Reporting Trials
(CONSORT) statement have been issued that would be expected to change practices
for adherence monitoring, analysis, and reporting. CONCLUSIONS: Adherence
measurement methodology and results are underreported in published RCTs. In the
minority of RCTs that provided adherence information, there was substantial
heterogeneity in how adherence was defined, analyzed, and reported. Improved
reporting of adherence may enhance the interpretation of study quality and
results.
PMID- 24357666
TI - Dipeptidyl peptidase-4 inhibitor reduces infarct size and preserves cardiac
function via mitochondrial protection in ischaemia-reperfusion rat heart.
AB - AIM: We hypothesized that dipeptidyl peptidase (DPP)-4 inhibitor (vildagliptin)
reduces fatal arrhythmias, cardiac dysfunction and infarct size caused by
ischaemia-reperfusion (I/R) injury via its attenuation of cardiac mitochondrial
dysfunction. METHODS: In total, 26 rats were randomized to receive either 1 mL
normal saline solution or 2.0 mg/kg vildagliptin intravenously (n = 13/group) 30
min prior to a 30-min left anterior descending coronary artery occlusion,
followed by a 120-min reperfusion. Arrhythmia scores, cardiac functions, infarct
size and mitochondrial function were evaluated. RESULTS: Vildagliptin reduced the
infarct size by 44% and mitigated cardiac dysfunction by preserving cardiac
function without altering the incidence of cardiac arrhythmias. Vildagliptin
increased expression of Bcl-2 and pro-caspase3 in the ischaemic area, whereas Bax
and phosphorylated-connexin43/total-connexin43 were not altered. Vildagliptin
attenuated cardiac mitochondrial dysfunction by reducing the reactive oxygen
species level and mitochondrial swelling. CONCLUSIONS: DPP-4 inhibitor provides
cardioprotection by reducing the infarct size and ameliorating cardiac
dysfunction in I/R hearts by attenuating cardiac mitochondrial dysfunction and
cardiomyocyte apoptosis.
PMID- 24357667
TI - If oxidative stress is an appropriate and specific target, what reagent should we
choose?
PMID- 24357668
TI - Clinical findings, pathology, and outcomes of C3GN after kidney transplantation.
AB - C3 glomerulonephritis (C3GN) results from abnormalities in the alternative
pathway of complement, and it is characterized by deposition of C3 with absent or
scant Ig deposition. In many patients, C3GN progresses to ESRD. The clinical
features, pathology, and outcomes of patients with C3GN receiving kidney
transplantation are unknown. Between 1996 and 2010, we identified 21 patients at
our institution who received a kidney transplant because of ESRD from C3GN. The
median age at the time of initial diagnosis of C3GN at kidney biopsy was 20.8
years. The median time from native kidney biopsy to dialysis or transplantation
was 42.3 months. Of 21 patients, 14 (66.7%) patients developed recurrent C3GN in
the allograft. The median time to recurrence of disease was 28 months. Graft
failure occurred in 50% of patients with recurrent C3GN, with a median time of 77
months to graft failure post-transplantation. The remaining 50% of patients had
functioning grafts, with a median follow-up of 73.9 months. The majority of
patients had hematuria and proteinuria at time of recurrence. Three (21%)
patients were positive for monoclonal gammopathy and had a faster rate of
recurrence and graft loss. Kidney biopsy at the time of recurrence showed
mesangial proliferative GN in eight patients and membranoproliferative GN in six
patients. All allograft kidney biopsies showed bright C3 staining (2-3+), with
six biopsies also showing trace/1+ staining for IgM and/or IgG. To summarize,
C3GN recurs in 66.7% of patients, and one half of the patients experience graft
failure caused by recurrence.
PMID- 24357669
TI - Estimating podocyte number and density using a single histologic section.
AB - The reduction in podocyte density to levels below a threshold value drives
glomerulosclerosis and progression to ESRD. However, technical demands prohibit
high-throughput application of conventional morphometry for estimating podocyte
density. We evaluated a method for estimating podocyte density using single
paraffin-embedded formalin-fixed sections. Podocyte nuclei were imaged using
indirect immunofluorescence detection of antibodies against Wilms' tumor-1 or
transducin-like enhancer of split 4. To account for the large size of podocyte
nuclei in relation to section thickness, we derived a correction factor given by
the equation CF=1/(D/T+1), where T is the tissue section thickness and D is the
mean caliper diameter of podocyte nuclei. Normal values for D were directly
measured in thick tissue sections and in 3- to 5-MUm sections using calibrated
imaging software. D values were larger for human podocyte nuclei than for rat or
mouse nuclei (P<0.01). In addition, D did not vary significantly between human
kidney biopsies at the time of transplantation, 3-6 months after transplantation,
or with podocyte depletion associated with transplant glomerulopathy. In rat
models, D values also did not vary with podocyte depletion, but increased
approximately 10% with old age and in postnephrectomy kidney hypertrophy. A
spreadsheet with embedded formulas was created to facilitate individualized
podocyte density estimation upon input of measured values. The correction factor
method was validated by comparison with other methods, and provided data
comparable with prior data for normal human kidney transplant donors. This method
for estimating podocyte density is applicable to high-throughput laboratory and
clinical use.
PMID- 24357670
TI - Neonatal Fc receptor promotes immune complex-mediated glomerular disease.
AB - The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin
homeostasis systemically and in the kidneys. We investigated the role of FcRn in
the development of immune complex-mediated glomerular disease in mice. C57Bl/6
mice immunized with the noncollagenous domain of the alpha3 chain of type IV
collagen (alpha3NC1) developed albuminuria associated with granular capillary
loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte
injury. High-resolution imaging showed abundant IgG deposition in the expanded
glomerular basement membrane, especially in regions corresponding to
subepithelial electron dense deposits. FcRn-null and -humanized mice immunized
with alpha3NC1 developed no albuminuria and had lower levels of serum IgG anti
alpha3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and
complement. Our results show that FcRn promotes the formation of subepithelial
immune complexes and subsequent glomerular pathology leading to proteinuria,
potentially by maintaining higher serum levels of pathogenic IgG antibodies.
Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may
provide a novel approach for the treatment of immune complex-mediated glomerular
diseases. As proof of concept, we showed that a peptide inhibiting the
interaction between human FcRn and human IgG accelerated the degradation of human
IgG anti-alpha3NC1 autoantibodies injected into FCRN-humanized mice as
effectively as genetic ablation of FcRn, thus preventing the glomerular
deposition of immune complexes containing human IgG.
PMID- 24357671
TI - Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and
protects against tubulointerstitial fibrosis.
AB - Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with
a pivotal role in kidney fibrosis. The interaction of TG2 with the heparan
sulfate proteoglycan syndecan-4 (Sdc4) regulates the cell surface trafficking,
localization, and activity of TG2 in vitro but remains unstudied in vivo. We
tested the hypothesis that Sdc4 is required for cell surface targeting of TG2 and
the development of kidney fibrosis in CKD. Wild-type and Sdc4-null mice were
subjected to unilateral ureteric obstruction and aristolochic acid nephropathy
(AAN) as experimental models of kidney fibrosis. Analysis of renal scarring by
Masson trichrome staining, kidney hydroxyproline levels, and collagen
immunofluorescence demonstrated progressive fibrosis associated with increases in
extracellular TG2 and TG activity in the tubulointerstitium in both models.
Knockout of Sdc-4 reduced these effects and prevented AAN-induced increases in
total and active TGF-beta1. In wild-type mice subjected to AAN, extracellular TG2
colocalized with Sdc4 in the tubular interstitium and basement membrane, where
TG2 also colocalized with heparan sulfate chains. Heparitinase I, which
selectively cleaves heparan sulfate, completely abolished extracellular TG2 in
normal and diseased kidney sections. In conclusion, the lack of Sdc4 heparan
sulfate chains in the kidneys of Sdc4-null mice abrogates injury-induced
externalization of TG2, thereby preventing profibrotic crosslinking of
extracellular matrix and recruitment of large latent TGF-beta1. This finding
suggests that targeting the TG2-Sdc4 interaction may provide a specific
interventional strategy for the treatment of CKD.
PMID- 24357673
TI - Urinary biomarkers of AKI and mortality 3 years after cardiac surgery.
AB - Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but
little is known about their association with longer-term mortality after surgery.
We sought to assess the association between kidney injury biomarkers and all
cause mortality in an international, multicenter, prospective long-term follow-up
study from six clinical centers in the United States and Canada composed of 1199
adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in
the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative
days 1-3, we measured the following five urinary biomarkers: neutrophil
gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver
fatty acid binding protein, and albumin. During a median follow-up of 3.0 years
(interquartile range, 2.2-3.6 years), 139 participants died (55 deaths per 1000
person-years). Among patients with clinical AKI, the highest tertiles of peak
urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty
acid binding protein, and albumin associated independently with a 2.0- to 3.2
fold increased risk for mortality compared with the lowest tertiles. In patients
without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also
associated independently with long-term mortality (adjusted hazard ratios [95%
confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM
1, respectively), and yielded continuous net reclassification improvements of
0.26 and 0.37, respectively, for the prediction of 3-year mortality. In
conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in
the immediate postoperative period provide additional prognostic information for
3-year mortality risk in patients with and without clinical AKI.
PMID- 24357672
TI - Rapid and efficient differentiation of human pluripotent stem cells into
intermediate mesoderm that forms tubules expressing kidney proximal tubular
markers.
AB - Human pluripotent stem cells (hPSCs) can generate a diversity of cell types, but
few methods have been developed to derive cells of the kidney lineage. Here, we
report a highly efficient system for differentiating human embryonic stem cells
and induced pluripotent stem cells (referred to collectively as hPSCs) into cells
expressing markers of the intermediate mesoderm (IM) that subsequently form
tubule-like structures. Treatment of hPSCs with the glycogen synthase kinase
3beta inhibitor CHIR99021 induced BRACHYURY(+)MIXL1(+) mesendoderm
differentiation with nearly 100% efficiency. In the absence of additional
exogenous factors, CHIR99021-induced mesendodermal cells preferentially
differentiated into cells expressing markers of lateral plate mesoderm with
minimal IM differentiation. However, the sequential treatment of hPSCs with
CHIR99021 followed by fibroblast growth factor-2 and retinoic acid generated
PAX2(+)LHX1(+) cells with 70%-80% efficiency after 3 days of differentiation.
Upon growth factor withdrawal, these PAX2(+)LHX1(+) cells gave rise to apically
ciliated tubular structures that coexpressed the proximal tubule markers Lotus
tetragonolobus lectin, N-cadherin, and kidney-specific protein and partially
integrated into embryonic kidney explant cultures. With the addition of FGF9 and
activin, PAX2(+)LHX1(+) cells specifically differentiated into cells expressing
SIX2, SALL1, and WT1, markers of cap mesenchyme nephron progenitor cells. Our
findings demonstrate the effective role of fibroblast growth factor signaling in
inducing IM differentiation in hPSCs and establish the most rapid and efficient
system whereby hPSCs can be differentiated into cells with features
characteristic of kidney lineage cells.
PMID- 24357675
TI - EEG Database of Seizure Disorders for Experts and Application Developers.
AB - This article presents an online accessible electroencephalogram (EEG) database,
where the EEG recordings comprise abnormal patterns such as spikes, poly spikes,
slow waves, and sharp waves to help diagnose related disorders. The data, as of
now, are a collection of EEGs from a diagnostic center in Coimbatore, Tamil Nadu,
India, and the data samples pertain to an age-group ranging from 1 to 107 years.
Eventually, the EEG data concerning other disorders as well as those from other
institutions will be included. The present database provides information under
the following categories: major classification of the disorder, patient's record,
digitized EEG, and specific diagnosis; in addition, a search facility is
incorporated into the database. The mode of access by the domain experts,
application developers, and researchers, along with a few classical applications
are explained in this article. With the advance of clinical neuroscience, this
database will be helpful in developing software for applications such as
diagnosis and treatment.
PMID- 24357674
TI - Cubilin maintains blood levels of HDL and albumin.
AB - Cubilin is an endocytic receptor highly expressed in renal proximal tubules,
where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin
deficiency leads to urinary loss of albumin and apoA-I; however, the consequences
of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been
studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we
show that cubilin haploinsufficiency leads to reduced renal proximal tubular
uptake of albumin and apoA-I and significantly increased urinary loss of albumin
and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood
levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or
mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not
change significantly. The clearance rate of small HDL3 particles (density>1.13
g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the
rate of clearance of larger HDL2 particles from the blood did not change
significantly, indicating a decreased half-life for HDL particles capable of
filtering through the glomerulus. On the basis of these findings, we conclude
that cubilin deficiency reduces renal salvage and delivery back to the blood of
albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These
findings raise the possibility that therapeutic increase of renal cubilin
expression might reduce proteinuria and increase blood levels of albumin and HDL.
PMID- 24357676
TI - The safety and tolerability of different intravenous administrations of
levetiracetam, bolus versus infusion, in intensive care unit patients.
AB - This study reviews our experience with the safety and tolerability of
levetiracetam (LVM) with different methods of intravenous administration in
intensive care unit (ICU) patients. We used retrospective chart review to
identify 33 ICU patients who received intravenous LVM for treatment of seizures.
Collected data included age, gender, diagnosis on admission, dosing regimen,
documented seizure activity, adverse reactions, concomitant use of other
antiepileptic drugs, and condition on discharge. A total of 33 ICU patients were
given intravenous (IV) LVM as add-on treatment to standard regimen for treatment
of breakthrough seizures or status epilepticus or given as preventive medication
postoperatively. Among these 33 patients, 16 received intravenous LVM as bolus,
and 17 received intravenous LVM as continuous infusion. Safety and tolerability
of intravenous LVM were evaluated on the basis of the occurrence of adverse or
side effects reported in daily progress notes of the physicians and nurses. There
were no significant adverse or side effects reported in daily progress notes. The
addition of intravenous LVM to the standard regimen for controlling seizures in
ICU patients seems feasible and tolerable.
PMID- 24357677
TI - Epilepsy and electrophysiological findings in polish twins with glycogenosis type
IIIb.
AB - Glycogen storage diseases are rare genetic disorders, mostly autosomal
recessively inherited. Abnormal accumulation is because of the lack of one of the
enzymes involved in glycogen metabolism. Neurological manifestation of the
diseases involves muscle weakness and hypoglycemia-induced seizures. In this
article, we present a history of twin sisters with unusual coincidence of
glycogenosis type IIIb and epilepsy. Hypoglycemic background of seizures and
organic changes of the central nervous system were excluded. Since the
introduction of antiepileptic treatment, the patients have been seizure-free;
however, paroxysmal electroencephalographic (EEG) changes have persisted. A high
protein and low-carbohydrate diet has protected them against hypoglycemia.
PMID- 24357678
TI - Percutaneous osteotomy for irreducible or malunited tongue-type calcaneus
fractures.
PMID- 24357679
TI - Surgical technique, fusion rates, and planovalgus foot deformity correction with
naviculocuneiform fusion.
AB - BACKGROUND: Arthrodesis of the naviculocuneiform (NC) joints is not a common
procedure, as it is perceived by many to be less reliable or less predictable
than arthrodesis of proximal or distal joints in the medial column. There is a
subset of patients with planovalgus feet, cavovarus feet, and degenerative
arthritis who also have an apex of deformity at the NC joints in whom fusion is
indicated. The surgical technique, fusion rates, and deformity correction data
for NC fusion in planovalgus feet are evaluated in this report. METHODS: Twenty
eight patients (33 feet) who underwent surgery between October 2008 and November
2012 were identified who had NC fusion as their only arthrodesis procedure.
Medical records and radiographs were reviewed, and time to union was calculated.
Twenty patients from that group underwent NC fusion for symptomatic planovalgus
feet, and their preoperative and last postoperative weight-bearing radiographs
were reviewed and compared for deformity correction. All patients were operated
on by the senior author or a senior foot and ankle trainee during fellowship
using the same surgical technique, and all patients followed a standardized
postoperative rehabilitation protocol. RESULTS: Mean time to union for all 33 NC
fusions was 21.7 +/- 2 weeks (mean +/- SEM). One patient underwent revision for
nonunion, resulting in an arthrodesis rate of 97%. For NC fusions in those with
planovalgus feet, an improvement in mean lateral talus-first metatarsal angle
(Meary's line) from 12.3 +/- 1.3 degrees to 5.2 +/- 1.2 degrees (P < .05) was
found. There was also a mean improvement in talonavicular coverage angle from
14.1 +/- 1.8 degrees to 7.4 +/- 1.3 degrees (P < .05). There were 2 superficial
wound infections that were successfully treated with oral antibiotics, there were
no cases of deep vein thrombosis or pulmonary embolism, and all patients came out
of cast at 6 weeks into a fixed angle boot to commence weight bearing. Patients
were happy with 32 of the 33 procedures and required no further treatment for
their condition. CONCLUSIONS: NC fusion was a safe and predictable procedure for
any of its indications, with a fusion rate similar to that of other joints in the
foot albeit with a longer time to union. For patients with symptomatic and
flexible planovalgus feet, NC fusion resulted in deformity correction in multiple
planes and good symptomatic relief. LEVEL OF EVIDENCE: Level IV, retrospective
case series.
PMID- 24357680
TI - Trends in treatment of advanced ankle arthropathy by total ankle replacement or
ankle fusion.
AB - BACKGROUND: Total ankle replacement (TAR) and ankle fusion (AF) are the 2 major
operative options for treatment of advanced ankle arthropathy; there is, however,
no large epidemiologic study comparing nationwide trends of these 2 procedures.
The current study used a nationwide database to compare epidemiologic profiles of
TAR and AF. METHODS: Data collected for the Nationwide Inpatient Sample (NIS)
from 2000 to 2010 were reviewed. Procedures were identified by searching for ICD
9-CM codes 81.11 (AF) and 81.56 (TAR). Patients' demographics and comorbidities,
geographic distribution, and cost of procedures were compared. RESULTS: The NIS
analysis identified 2666 TAR and 16 419 AF cases which was extrapolated to 13 145
TAR and 80 426 AF nationwide. Spearman's rho showed an increase in the number of
AF per year while the number of TAR cases remained relatively flat per year until
2006, after which there was a steady increase in the number of TAR performed.
Patients receiving a TAR tended to be older, female, and white. Patients who
underwent AF were more likely to be obese or diabetic than TAR patients. Both TAR
and AF were performed more frequently in private urban hospitals through 2007.
However, in 2010, the number of TAR procedures was greater in academic centers
compared to private urban hospitals. CONCLUSIONS: Despite recent increases in the
number of TAR implanted, AF was still performed more than 6 times more frequently
for advanced ankle arthropathy. A trend was demonstrated toward an increasing
number of TAR being implanted in academic centers, and in patients with more
underlying comorbidities than was previously seen. LEVEL OF EVIDENCE: Level II,
prognostic study.
PMID- 24357681
TI - Is the Pill Questionnaire useless? Your move, MDS Task Force.
PMID- 24357682
TI - Guillain-Barre syndrome in Asia.
AB - Over the past 20 years, the most notable advance in understanding Guillain-Barre
syndrome (GBS) has been the identification of an axonal variant. This advance
arose chiefly through studies undertaken in East Asian countries and comprised
two major aspects: first, the immunopathogenesis of axonal GBS related to anti
ganglioside antibodies and molecular mimicry of Campylobacter jejuni; and second,
the observation that distinct electrophysiological patterns of axonal GBS
existed, reflecting reversible conduction failure (RCF). As a consequence, the
pathophysiology of acute motor axonal neuropathy (AMAN) has perhaps become better
understood than acute inflammatory demyelinating polyneuropathy. Despite these
more recent advances, a critical issue remains largely unresolved: whether axonal
GBS is more common in Asia than in Europe or North America. If it is more common
in Asia, then causative factors must be more critically considered, including
geographical differences, issues of genetic susceptibility, the role of
antecedent infections and other potential triggering factors. It has become
apparent that the optimal diagnosis of AMAN requires serial electrophysiological
testing, to better delineate RCF, combined with assessment for the presence of
anti-ganglioside antibodies. Recent collaborative approaches between Europe and
Asia have suggested that both the electrophysiological pattern of AMAN and the
seropositivity for anti-ganglioside antibodies develop similarly. Separately,
however, current electrodiagnostic criteria for AMAN limited to a single
assessment appear inadequate to identify the majority of cases. As such,
diagnostic criteria will need to be revised to improve the diagnostic sensitivity
for AMAN.
PMID- 24357683
TI - Appreciation of CT-negative, lumbar puncture-positive subarachnoid haemorrhage:
risk factors for presence of aneurysms and diagnostic yield of imaging.
AB - OBJECTIVE: Patients without a subarachnoid haemorrhage (SAH) on brain CT scan (CT
negative), but a lumbar puncture (LP)-proven SAH, are a challenging patient
category. The optimal diagnostic approach is still a matter of debate. Also,
there is little knowledge on the probability of finding an underlying vascular
lesion. DESIGN: In this observational study, a consecutive cohort of 94 patients
with CT-negative, LP-positive SAH was prospectively collected between 1998 and
2013. The yield of diagnostic modalities as well as patient outcome was studied.
In addition, risk factors for the presence of a vascular lesion were analysed.
RESULTS: In 40 patients (43%), an intracranial vascular abnormality was detected:
37 aneurysms and three arterial dissections. Female gender was significantly
associated with detection of a vascular lesion. Time between ictus and diagnosis
of SAH was not associated with the presence of vascular pathology. Overall, 99%
of patients had a modified Rankin Score of 0-2 after a median follow-up of 72
months. The yield of additional digital subtraction angiography in patients with
a negative CT angiography was zero. CONCLUSIONS: In this study, the chance of
finding a vascular lesion in a patient with CT-negative, LP-positive SAH was 43%,
underlining the need for an adequate diagnostic workup. In general, the patient
outcome was favourable. Female gender was found to be predictive for detecting a
vascular lesion. In contrast with previous reports, the interval between ictus
and LP was not associated with the presence of an aneurysm.
PMID- 24357684
TI - Central motor conduction time may predict response to fampridine in patients with
multiple sclerosis.
PMID- 24357685
TI - A practical approach to diagnosing adult onset leukodystrophies.
PMID- 24357686
TI - Multicenter harmonization of 89Zr PET/CT performance.
AB - This study investigated the feasibility of quantitative accuracy and harmonized
image quality in (89)Zr-PET/CT multicenter studies. METHODS: Five PET/CT scanners
from 3 vendors were included. (89)Zr activity was measured in a central dose
calibrator before delivery. Local activity assays were based on volume as well as
on the local dose calibrator. Accuracy and image noise were determined from a
cross calibration experiment. Image quality was assessed from recovery
coefficients derived from different volume-of-interest (VOI) methods (VOI A 50%,
based on a 3-dimensional isocontour at 50% of the maximum voxel value with local
background correction; VOI Max, based on the voxel with the highest uptake; and
VOI 3Dpeak, based on a spheric VOI of 1.2-cm diameter positioned so as to
maximize the enclosed average). PET images were analyzed before and after
postreconstruction smoothing, applied to match image noise. RESULTS: PET/CT
accuracy and image noise ranged from -3% to 10% and from 13% to 22%,
respectively. VOI 3Dpeak produced the most reproducible recovery coefficients.
After calibration of the local dose calibrator to the central dose calibrator,
differences between the local activity assays were within 6%. CONCLUSION: This
study showed that quantitative accuracy and harmonized image quality can be
reached in (89)Zr PET/CT multicenter studies.
PMID- 24357688
TI - The beta-cell/EC axis: how do islet cells talk to each other?
AB - Within the pancreatic islet, the beta-cell represents the ultimate biosensor. Its
central function is to accurately sense glucose levels in the blood and
consequently release appropriate amounts of insulin. As the only cell type
capable of insulin production, the beta-cell must balance this crucial workload
with self-preservation and, when required, regeneration. Evidence suggests that
the beta-cell has an important ally in intraislet endothelial cells (ECs). As
well as providing a conduit for delivery of the primary input stimulus (glucose)
and dissemination of its most important effector (insulin), intraislet blood
vessels deliver oxygen to these dense clusters of metabolically active cells.
Furthermore, it appears that ECs directly impact insulin gene expression and
secretion and beta-cell survival. This review discusses the molecules and
pathways involved in the crosstalk between beta-cells and intraislet ECs. The
evidence supporting the intraislet EC as an important partner for beta-cell
function is examined to highlight the relevance of this axis in the context of
type 1 and type 2 diabetes. Recent work that has established the potential of ECs
or their progenitors to enhance the re-establishment of glycemic control
following pancreatic islet transplantation in animal models is discussed.
PMID- 24357689
TI - Death and dysfunction of transplanted beta-cells: lessons learned from type 2
diabetes?
AB - beta-Cell replacement by islet transplantation is a potential curative therapy
for type 1 diabetes. Despite advancements in islet procurement and immune
suppression that have increased islet transplant survival, graft function
progressively declines, and many recipients return to insulin dependence within a
few years posttransplant. The progressive loss of beta-cell function in islet
transplants seems unlikely to be explained by allo- and autoimmune-mediated
mechanisms alone and in a number of ways resembles beta-cell failure in type 2
diabetes. That is, both following transplantation and in type 2 diabetes, islets
exhibit decreased first-phase glucose-stimulated insulin secretion, impaired
proinsulin processing, inflammation, formation of islet amyloid, signs of
oxidative and endoplasmic reticulum stress, and beta-cell death. These
similarities suggest common mechanisms may underlie loss of insulin production in
both type 2 diabetes and islet transplantation and point to the potential for
therapeutic approaches used in type 2 diabetes that target the beta-cell, such as
incretin-based therapies, as adjuncts for immunosuppression in islet
transplantation.
PMID- 24357691
TI - Red wine and diabetes health: getting skin in the game.
PMID- 24357690
TI - It's time to bring dendritic cell therapy to type 1 diabetes.
PMID- 24357692
TI - New thoughts in an old player: role of nitrite in the treatment of ischemic
revascularization.
PMID- 24357693
TI - Serum TAG analysis differentiates between genetic and obesity-associated NAFLD.
PMID- 24357694
TI - Implications for glucose measures in the diabetes control and complications
trial/epidemiology of diabetes interventions and complications study.
PMID- 24357695
TI - Endoplasmic reticulum: an interface between the immune system and metabolism.
PMID- 24357696
TI - The critical role of methylglyoxal and glyoxalase 1 in diabetic nephropathy.
PMID- 24357697
TI - Diabetes in South Asians: is the phenotype different?
PMID- 24357698
TI - A new tool for dissecting genetic control of type 1 diabetes.
PMID- 24357699
TI - Mitochondrial involvement in skeletal muscle insulin resistance.
PMID- 24357700
TI - Brain MRI in children with type 1 diabetes: snapshot or road map of developmental
changes?
PMID- 24357701
TI - The long and short of telomere length and diabetes.
PMID- 24357702
TI - A 5-day high-fat, high-calorie diet impairs insulin sensitivity in healthy, young
South Asian men but not in Caucasian men.
AB - South Asians (SAs) develop type 2 diabetes at a younger age and lower BMI
compared with Caucasians (Cs). The underlying cause is still poorly understood
but might result from an innate inability to adapt to the Westernized diet. This
study aimed to compare the metabolic adaptation to a high-fat, high-calorie
(HFHC) diet between both ethnicities. Twelve healthy, young lean male SAs and 12
matched Cs underwent a two-step hyperinsulinemic-euglycemic clamp with skeletal
muscle biopsies and indirect calorimetry before and after a 5-day HFHC diet.
Hepatic triglyceride content (HTG) and abdominal fat distribution were assessed
using magnetic resonance imaging and spectroscopy. At baseline, SAs had higher
insulin clamp levels than Cs, indicating reduced insulin clearance rate. Despite
the higher insulin levels, endogenous glucose production was comparable between
groups, suggesting lower hepatic insulin sensitivity in SAs. Furthermore, a 5-day
HFHC diet decreased the insulin-stimulated (nonoxidative) glucose disposal rate
only in SA. In skeletal muscle, no significant differences were found between
groups in insulin/mammalian target of rapamycin signaling, metabolic gene
expression, and mitochondrial respiratory chain content. Furthermore, no
differences in (mobilization of) HTG and abdominal fat were detected. We conclude
that HFHC feeding rapidly induces insulin resistance only in SAs. Thus, distinct
adaptation to Western food may partly explain their propensity to develop type 2
diabetes.
PMID- 24357703
TI - Multiple HLA epitopes contribute to type 1 diabetes susceptibility.
AB - Disease susceptibility for type 1 diabetes is strongly associated with the
inheritance of specific HLA alleles. However, conventional allele frequency
analysis can miss HLA associations because many alleles are rare. In addition,
disparate alleles that have similar peptide-binding sites, or shared epitopes,
can be missed. To identify the HLA shared epitopes associated with diabetes, we
analyzed high-resolution genotyping for class I and class II loci. The HLA
epitopes most strongly associated with susceptibility for disease were DQB1
A(57), DQA1 V(76), DRB1 H(13), and DRB1 K(71), whereas DPB1 YD(9,57), HLA-B
C(67), and HLA-C YY(9,116) were more weakly associated. The HLA epitopes strongly
associated with resistance were DQB1 D(57), DQA1 Y(80), DRB1 R(13), and DRB1
A(71). A dominant resistance phenotype was observed for individuals bearing a
protective HLA epitope, even in the presence of a susceptibility epitope. In
addition, an earlier age of disease onset correlated with significantly greater
numbers of susceptibility epitopes and fewer resistance epitopes (P < 0.0001).
The prevalence of both DQ and DR susceptibility epitopes was higher in patients
than in control subjects and was not exclusively a result of linkage
disequilibrium, suggesting that multiple HLA epitopes may work together to
increase the risk of developing diabetes.
PMID- 24357705
TI - IL-7Ralpha: Mr Hyde's twists and turns.
AB - In the current issue of Blood, Yokoyama et al demonstrate that an IL7R mutation
similar to those found in patients with acute lymphoblastic leukemia (ALL) can be
leukemogenic in vivo when expressed in normal hematopoietic progenitors.
PMID- 24357706
TI - Activated DDR1 increases RS cell survival.
AB - In this issue of Blood, Cader et al show that tumor microenvironment promotes
Epstein-Barr virus (EBV)-driven lymphomagenesis in Hodgkin lymphoma by a novel
pathway involving latent membrane protein 1 (LMP1) and discoidin domain receptor
1 (DDR1), which is activated by collagen(s) and contributes to the survival of
Reed-Sternberg (RS) cells.
PMID- 24357707
TI - A novel prognostic scoring system for NLPHL.
AB - In this issue of Blood, Hartmann and colleagues from the German Hodgkin Study
Group (GHSG) conducted a review of pathologic features and clinical data from 423
patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) treated
across 9 of their prospective clinical trials. First, they determined that
patients with histologic variants have a higher chance of having advanced-stage
disease and a greater risk for disease progression or relapse at 5 years. Second,
they were able to establish a prognostic scoring model that defines 3 discrete
risk groups based on the factors of variant histopathologic growth pattern, low
serum albumin, and male gender.
PMID- 24357708
TI - Cyclophosphamide for CLL: to be or not CYP2B activated?
PMID- 24357709
TI - A new view of integrin alphaIIbbeta3 bound to membrane.
AB - In this issue of Blood, Choi et al report a 3-dimensional (3D) reconstruction
model of integrin aIIbb3 in its latent state which challenges the existing
paradigm and provides new insights into the mechanism of integrin activation.
PMID- 24357710
TI - Superficial venous thrombosis: recognizing the risk.
AB - In this issue of Blood, Roach and colleagues show that individuals with prior
superficial venous thrombosis are at increased risk of developing venous
thromboembolism when exposed to acquired clinical risk factors.
PMID- 24357711
TI - Factor VIII inhibitor epitopes and an enigma.
AB - In this issue of Blood, Walter et al provide an x-ray crystallographic structure
of the factor VIII C2 domain in complex with 2 antibodies that illuminates how
inhibitory antibodies complicate hemophilia A therapy.
PMID- 24357712
TI - Resolution of thrombocytopenia with JAK2 mutation in a patient with Gaucher
disease.
PMID- 24357713
TI - Treatment of NLPHL.
PMID- 24357714
TI - Homozygosity by descent of a 3Mb chromosome 17 haplotype causes coinheritance of
Glanzmann thrombasthenia and primary ciliary dyskinesia.
PMID- 24357716
TI - Histone chaperone FACT regulates homologous recombination by chromatin remodeling
through interaction with RNF20.
AB - The E3 ubiquitin ligase RNF20 regulates chromatin structure through
ubiquitylation of histone H2B, so that early homologous recombination repair
(HRR) proteins can access the DNA in eukaryotes during repair. However, it
remains unresolved how RNF20 itself approaches the DNA in the presence of
chromatin structure. Here, we identified the histone chaperone FACT as a key
protein in the early steps of HRR. Depletion of SUPT16H, a component of FACT,
caused pronounced defects in accumulations of repair proteins and, consequently,
decreased HRR activity. This led to enhanced sensitivity to ionizing radiation
(IR) and mitomycin-C in a fashion similar to RNF20-deficient cells, indicating
that SUPT16H is essential for RNF20-mediated pathway. Indeed, SUPT16H directly
bound to RNF20 in vivo, and mutation at the RING-finger domain in RNF20 abolished
its interaction and accumulation, as well as that of RAD51 and BRCA1, at sites of
DNA double-strand breaks (DSBs), whereas the localization of SUPT16H remained
intact. Interestingly, PAF1, which has been implicated in transcription as a
mediator of FACT and RNF20 association, was dispensable for DNA-damage-induced
interaction of RNF20 with SUPT16H. Furthermore, depletion of SUPT16H caused
pronounced defects in RNF20-mediated H2B ubiquitylation and thereby, impaired
accumulation of the chromatin remodeling factor SNF2h. Consistent with this
observation, the defective phenotypes of SUPT16H were effectively counteracted by
enforced nucleosome relaxation. Taken together, our results indicate a primary
role of FACT in RNF20 recruitment and the resulting chromatin remodeling for
initiation of HRR.
PMID- 24357717
TI - Time-resolved quantitative proteomics implicates the core snRNP protein SmB
together with SMN in neural trafficking.
AB - The biogenesis of splicing snRNPs (small nuclear ribonucleoproteins) is a complex
process, beginning and ending in the nucleus of the cell but including key stages
that take place in the cytoplasm. In particular, the SMN (survival motor neuron)
protein complex is required for addition of the core Sm proteins to the snRNP.
Insufficiency of SMN results in the inherited neurodegenerative condition, spinal
muscular atrophy (SMA). Details of the physical organization of the cytoplasmic
stages of snRNP biogenesis are unknown. Here, we use time-resolved quantitative
proteomics to identify proteins that associate preferentially with either newly
assembled or mature splicing snRNPs. We identified highly mobile SmB protein
trafficking vesicles in neural cells, which are dependent on the cellular levels
of SMN and SmB for their morphology and mobility. We propose that these represent
a family of related vesicles, some of which play a role in snRNP biogenesis and
some that might play more diverse roles in cellular RNA metabolism.
PMID- 24357719
TI - Low-force transitions in single titin molecules reflect a memory of contractile
history.
AB - Titin is a giant elastomeric muscle protein that has been suggested to function
as a sensor of sarcomeric stress and strain, but the mechanisms by which it does
so are unresolved. To gain insight into its mechanosensory function we
manipulated single titin molecules with high-resolution optical tweezers.
Discrete, step-wise transitions, with rates faster than canonical Ig domain
unfolding occurred during stretch at forces as low as 5 pN. Multiple mechanisms
and molecular regions (PEVK, proximal tandem-Ig, N2A) are likely to be involved.
The pattern of transitions is sensitive to the history of contractile events.
Monte-Carlo simulations of our experimental results predicted that structural
transitions begin before the complete extension of the PEVK domain. High
resolution atomic force microscopy (AFM) supported this prediction. Addition of
glutamate-rich PEVK domain fragments competitively inhibited the viscoelastic
response in both single titin molecules and muscle fibers, indicating that PEVK
domain interactions contribute significantly to sarcomere mechanics. Thus, under
non-equilibrium conditions across the physiological force range, titin extends by
a complex pattern of history-dependent discrete conformational transitions,
which, by dynamically exposing ligand-binding sites, could set the stage for the
biochemical sensing of the mechanical status of the sarcomere.
PMID- 24357718
TI - Mitoneet mediates TNFalpha-induced necroptosis promoted by exposure to fructose
and ethanol.
AB - Fructose and ethanol are metabolized principally in the liver and are both known
to contribute to the development of hepatic steatosis that can progress to
hepatic steatohepatitis. The present study indentifies a synergistic interaction
between fructose and ethanol in promoting hepatocyte sensitivity to TNFalpha
induced necroptosis. Concurrent exposure to fructose and ethanol induces the
overexpression of the CDGSH iron-sulfur domain-containing protein 1 (CISD1 or
mitoneet), which is localized to the outer mitochondrial membrane. The increased
expression of mitoneet primes the hepatocyte for TNFalpha-induced cytotoxicity.
Treatment with TNFalpha induces the translocation of a Stat3-Grim-19 complex to
the mitochondria, which binds to mitoneet and promotes the rapid release of its
2Fe-2S cluster, causing an accumulation of mitochondrial iron. The dramatic
increase of mitochondrial iron provokes a surge in formation of reactive oxygen
species, resulting in mitochondrial injury and cell death. Additionally, mitoneet
is constitutively expressed at high levels in L929 fibrosarcoma cells and is
required for L929 cells to undergo TNFalpha-induced necroptosis in the presence
of caspase inhibition, indicating the importance of mitoneet to the necroptotic
form of cell death.
PMID- 24357720
TI - FGF2-induced Ras-MAPK signalling maintains lymphatic endothelial cell identity by
upregulating endothelial-cell-specific gene expression and suppressing TGFbeta
signalling through Smad2.
AB - The lymphatic endothelial cell (LEC) fate decision program during development has
been described. However, the mechanism underlying the maintenance of
differentiated LEC identity remains largely unknown. Here, we show that
fibroblast growth factor 2 (FGF2) plays a fundamental role in maintaining a
differentiated LEC trait. In addition to demonstrating the appearance of LECs
expressing alpha-smooth muscle actin in mouse lymphedematous skin in vivo, we
found that mouse immortalised LECs lose their characteristics and undergo
endothelial-to-mesenchymal transition (EndMT) when cultured in FGF2-depleted
medium. FGF2 depletion acted synergistically with transforming growth factor
(TGF) beta to induce EndMT. We also found that H-Ras-overexpressing LECs were
resistant to EndMT. Activation of H-Ras not only upregulated FGF2-induced
activation of the Erk mitogen activated protein kinases (MAPK3 and MAPK1), but
also suppressed TGFbeta-induced activation of Smad2 by modulating Smad2
phosphorylation by MAPKs. These results suggest that FGF2 regulates LEC-specific
gene expression and suppresses TGFbeta signalling in LECs through Smad2 in a Ras
MAPK-dependent manner. Taken together, our findings provide a new insight into
the FGF2-Ras-MAPK-dependent mechanism that maintains and modulates the LEC trait.
PMID- 24357721
TI - Annexin A2 mediates secretion of collagen VI, pulmonary elasticity and apoptosis
of bronchial epithelial cells.
AB - The annexins are an evolutionarily conserved family of phospholipid-binding
proteins of largely unknown function. We observed that the AnxA2(-/-) lung
basement membrane specifically lacks collagen VI (COL6), and postulated that
ANXA2 directs bronchial epithelial cell secretion of COL6, an unusually large
multimeric protein. COL6 serves to anchor cells to basement membranes and, unlike
other collagens, undergoes multimerization prior to secretion. Here, we show that
AnxA2(-/-) mice have reduced exercise tolerance with impaired lung tissue
elasticity, which was phenocopied in Col6a1(-/-) mice. In vitro, AnxA2(-/-)
fibroblasts retained COL6 within intracellular vesicles and adhered poorly to
their matrix unless ANXA2 expression was restored. In vivo, AnxA2(-/-) bronchial
epithelial cells underwent apoptosis and disadhesion. Immunoprecipitation and
immunoelectron microscopy revealed that ANXA2 associates with COL6 and the SNARE
proteins SNAP-23 and VAMP2 at secretory vesicle membranes of bronchial epithelial
cells, and that absence of ANXA2 leads to retention of COL6 in a late-Golgi,
VAMP2-positive compartment. These results define a new role for ANXA2 in the COL6
secretion pathway, and further show that this pathway establishes cell-matrix
interactions that underlie normal pulmonary function and epithelial cell
survival.
PMID- 24357723
TI - Sharp-1 regulates TGF-beta signaling and skeletal muscle regeneration.
AB - Sharp-1 is a basic helix-loop-helix (bHLH) transcriptional repressor that is
involved in a number of cellular processes. Our previous studies have
demonstrated that Sharp-1 is a negative regulator of skeletal myogenesis and it
blocks differentiation of muscle precursor cells by modulating the activity of
MyoD. In order to understand its role in pre- and post-natal myogenesis, we
assessed skeletal muscle development and freeze-injury-induced regeneration in
Sharp-1-deficient mice. We show that embryonic skeletal muscle development is not
impaired in the absence of Sharp-1; however, post-natally, the regenerative
capacity is compromised. Although the initial phases of injury-induced
regeneration proceed normally in Sharp-1(-/-) mice, during late stages, the
mutant muscle exhibits necrotic fibers, calcium deposits and fibrosis. TGF-beta
expression, as well as levels of phosphorylated Smad2 and Smad3, are sustained in
the mutant tissue and treatment with decorin, which blocks TGF-beta signaling,
improves the histopathology of Sharp-1(-/-) injured muscles. In vitro, Sharp-1
associates with Smad3, and its overexpression inhibits TGF-beta- and Smad3
mediated expression of extracellular matrix genes in myofibroblasts. These
results demonstrate that Sharp-1 regulates muscle regenerative capacity, at least
in part, by modulation of TGF-beta signaling.
PMID- 24357724
TI - Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid
receptor target genes in mouse embryonic fibroblasts.
AB - Nuclear retinoic acid (RA) receptors (RARalpha, beta and gamma) are ligand
dependent transcription factors that regulate the expression of a battery of
genes involved in cell differentiation and proliferation. They are also
phosphoproteins and we previously showed the importance of their phosphorylation
in their transcriptional activity. In the study reported here, we conducted a
genome-wide analysis of the genes that are regulated by RARs in mouse embryonic
fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We
found that in the absence of RA, RARs control the expression of several gene
transcripts associated with cell adhesion. Consequently the knockout MEFs are
unable to adhere and to spread on substrates and they display a disrupted network
of actin filaments, compared with the WT cells. In contrast, in the presence of
the ligand, RARs control the expression of other genes involved in signaling and
in RA metabolism. Taking advantage of rescue cell lines expressing the RARalpha
or RARgamma subtypes (either wild-type or mutated at the N-terminal
phosphorylation sites) in the null background, we found that the expression of RA
target genes can be controlled either by a specific single RAR or by a
combination of RAR isotypes, depending on the gene. We also selected genes that
require the phosphorylation of the receptors for their regulation by RA. Our
results increase the repertoire of genes that are regulated by RARs and highlight
the complexity and diversity of the transcriptional programs regulated by RARs,
depending on the gene.
PMID- 24357722
TI - Type VII collagen regulates expression of OATP1B3, promotes front-to-rear
polarity and increases structural organisation in 3D spheroid cultures of RDEB
tumour keratinocytes.
AB - Type VII collagen is the main component of anchoring fibrils, structures that are
integral to basement membrane homeostasis in skin. Mutations in the gene encoding
type VII collagen COL7A1 cause recessive dystrophic epidermolysis bullosa (RDEB)
an inherited skin blistering condition complicated by frequent aggressive
cutaneous squamous cell carcinoma (cSCC). OATP1B3, which is encoded by the gene
SLCO1B3, is a member of the OATP (organic anion transporting polypeptide)
superfamily responsible for transporting a wide range of endogenous and
xenobiotic compounds. OATP1B3 expression is limited to the liver in healthy
tissues, but is frequently detected in multiple cancer types and is reported to
be associated with differing clinical outcome. The mechanism and functional
significance of tumour-specific expression of OATP1B3 has yet to be determined.
Here, we identify SLCO1B3 expression in tumour keratinocytes isolated from RDEB
and UV-induced cSCC and demonstrate that SLCO1B3 expression and promoter activity
are modulated by type VII collagen. We show that reduction of SLCO1B3 expression
upon expression of full-length type VII collagen in RDEB cSCC coincides with
acquisition of front-to-rear polarity and increased organisation of 3D spheroid
cultures. In addition, we show that type VII collagen positively regulates the
abundance of markers implicated in cellular polarity, namely ELMO2, PAR3, E
cadherin, B-catenin, ITGA6 and Ln332.
PMID- 24357725
TI - Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta
mediated pregnancy complications.
AB - A 35-year-old woman with recurrent severe placenta-mediated pregnancy
complications in her 2 pregnancies asks: Will low-molecular-weight heparin help
prevent recurrent placenta-mediated pregnancy complications in my next pregnancy?
We performed a meta-analysis of randomized controlled trials (RCTs) comparing low
molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent
placenta-mediated pregnancy complications. We identified six RCTs that included a
total of 848 pregnant women with prior placenta-mediated pregnancy complications.
The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for
gestational-age (SGA) newborn (<10th percentile), placental abruption, or
pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given
prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications
compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction,
0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate
heterogeneity). We identified similar relative risk reductions with LMWH for
individual outcomes, including any PE, severe PE, SGA <10th percentile, SGA <5th
percentile, preterm delivery <37 weeks, and preterm delivery <34 weeks with
minimal heterogeneity. LMWH may be a promising therapy for recurrent, especially
severe, placenta-mediated pregnancy complications, but further research is
required.
PMID- 24357726
TI - Whole-genome integrative analysis reveals expression signatures predicting
transformation in follicular lymphoma.
AB - Transformation of follicular lymphoma (FL) to a more aggressive disease is
associated with rapid progression and death. Existing molecular markers for
transformation are few and their clinical impact is limited. Here, we report on a
whole-genome study of DNA copy numbers and gene expression profiles in serial FL
biopsies. We identified 698 genes with high correlation between gene expression
and copy number, and the molecular network most enriched for these cis-associated
genes. This network includes 14 cis-associated genes directly related to the
nuclear factor kappaB (NF-kappaB) pathway. For each of these 14 genes, the
correlated NF-kappaB target genes were identified and corresponding expression
scores were defined. The scores for 6 of the cis-associated NFkappaB pathway
genes (BTK, IGBP1, IRAK1, ROCK1, TMED7-TICAM2, and TRIM37) were significantly
associated with transformation. The results suggest that genes regulating B-cell
survival and activation are involved in transformation of FL.
PMID- 24357727
TI - A meta-analysis of genome-wide association studies identifies ORM1 as a novel
gene controlling thrombin generation potential.
AB - Thrombin, the major enzyme of the hemostatic system, is involved in biological
processes associated with several human diseases. The capacity of a given
individual to generate thrombin, called the thrombin generation potential (TGP),
can be robustly measured in plasma and was shown to associate with thrombotic
disorders. To investigate the genetic architecture underlying the interindividual
TGP variability, we conducted a genome-wide association study in 2 discovery
samples (N = 1967) phenotyped for 3 TGP biomarkers, the endogenous thrombin
potential, the peak height, and the lag time, and replicated the main findings in
2 independent studies (N = 1254). We identified the ORM1 gene, coding for
orosomucoid, as a novel locus associated with lag time variability, reflecting
the initiation process of thrombin generation with a combined P value of P = 7.1
* 10(-15) for the lead single nucleotide polymorphism (SNP) (rs150611042). This
SNP was also observed to associate with ORM1 expression in monocytes (P = 8.7 *
10(-10)) and macrophages (P = 3.2 * 10(-3)). In vitro functional experiments
further demonstrated that supplementing normal plasma with increasing orosomucoid
concentrations was associated with impaired thrombin generation. These results
pave the way for novel mechanistic pathways and therapeutic perspectives in the
etiology of thrombin-related disorders.
PMID- 24357728
TI - A mouse model of anemia of inflammation: complex pathogenesis with partial
dependence on hepcidin.
AB - Anemia is a common complication of infections and inflammatory diseases, but the
few mouse models of this condition are not well characterized. We analyzed in
detail the pathogenesis of anemia induced by an injection of heat-killed Brucella
abortus and examined the contribution of hepcidin by comparing wild-type (WT) to
iron-depleted hepcidin-1 knockout (Hamp-KO) mice. B abortus-treated WT mice
developed severe anemia with a hemoglobin nadir at 14 days and partial recovery
by 28 days. After an early increase in inflammatory markers and hepcidin, WT mice
manifested hypoferremia, despite iron accumulation in the liver. Erythropoiesis
was suppressed between days 1 and 7, and erythrocyte destruction was increased as
evidenced by schistocytes on blood smears and shortened red blood cell lifespan.
Erythropoietic recovery began after 14 days but was iron restricted. In B abortus
treated Hamp-KO compared with WT mice, anemia was milder, not iron restricted,
and had a faster recovery. Similarly to severe human anemia of inflammation, the
B abortus model shows multifactorial pathogenesis of inflammatory anemia
including iron restriction from increased hepcidin, transient suppression of
erythropoiesis, and shortened erythrocyte lifespan. Ablation of hepcidin relieves
iron restriction and improves the anemia.
PMID- 24357729
TI - Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice
injected with heat-killed Brucella abortus.
AB - Anemia of inflammation (AI) is commonly observed in chronic inflammatory states
and may hinder patient recovery and survival. Induction of hepcidin, mediated by
interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several
translational studies have been directed at neutralizing hepcidin overexpression
as a therapeutic strategy against AI. However, additional hepcidin-independent
mechanisms contribute to AI, which are likely mediated by a direct effect of
inflammatory cytokines on erythropoiesis. In this study, we used wild-type,
hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models
of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles
of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were
investigated. BA-treated wild-type mice showed increased expression of hepcidin
and inflammatory cytokines, as well as transitory suppression of erythropoiesis
and shortened red blood cell lifespan, all of which contributed to the severe
anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed
milder anemia and faster recovery compared with normal mice. Moreover, they
exhibited different patterns in the development and resolution of anemia,
supporting the notion that interleukin 6 and hepcidin play distinct roles in
modulating erythropoiesis in AI.
PMID- 24357730
TI - Reversal of in situ T-cell exhaustion during effective human antileukemia
responses to donor lymphocyte infusion.
AB - Increasing evidence across malignancies suggests that infiltrating T cells at the
site of disease are crucial to tumor control. We hypothesized that marrow
infiltrating immune populations play a critical role in response to donor
lymphocyte infusion (DLI), an established and potentially curative immune therapy
whose precise mechanism remains unknown. We therefore analyzed marrow
infiltrating immune populations in 29 patients (22 responders, 7 nonresponders)
with relapsed chronic myelogenous leukemia who received CD4(+) DLI in the pre
tyrosine kinase inhibitor era. Immunohistochemical analysis of pretreatment
marrow revealed that the presence of >4% marrow-infiltrating CD8(+) (but not
CD4(+)) T cells predicted DLI response, even in the setting of high leukemia
burden. Furthermore, mRNA expression profiling of marrow-infiltrating T cells of
a subset of responders compared with nonresponders revealed enrichment of T-cell
exhaustion-specific genes in pretreatment T cells of DLI responders and
significant downregulation of gene components in the same pathway in responders
in conjunction with clinical response. Our data demonstrate that response to DLI
is associated with quantity of preexisting marrow CD8(+) T cells and local
reversal of T-cell exhaustion. Our studies implicate T-cell exhaustion as a
therapeutic target of DLI and support the potential use of novel anti-PD1/PDL1
agents in lieu of DLI.
PMID- 24357731
TI - B-cell tolerance regulates production of antibodies causing heparin-induced
thrombocytopenia.
AB - Immune complexes consisting of heparin, platelet factor 4 (PF4), and PF4/heparin
reactive antibodies are central to the pathogenesis of heparin-induced
thrombocytopenia (HIT). It is as yet unclear what triggers the initial induction
of pathogenic antibodies. We identified B cells in peripheral blood of healthy
adults that produce PF4/heparin-specific antibodies following in vitro
stimulation with proinflammatory molecules containing deoxycytosine
deoxyguanosine (CpG). Similarly, B cells from unmanipulated wild-type mice
produced PF4/heparin-specific antibodies following in vitro or in vivo CpG
stimulation. Thus, both healthy humans and mice possess preexisting
inactive/tolerant PF4/heparin-specific B cells. The findings suggest that
breakdown of tolerance leads to PF4/heparin-specific B-cell activation and
antibody production in patients developing HIT. Consistent with this concept,
mice lacking protein kinase Cdelta (PKCdelta) that are prone to breakdown of B
cell tolerance produced anti-PF4/heparin antibodies spontaneously. Therefore,
breakdown of tolerance can lead to PF4/heparin-specific antibody production, and
B-cell tolerance may play an important role in HIT pathogenesis.
PMID- 24357733
TI - Metallic or bioabsorbable interference screw for graft fixation in anterior
cruciate ligament (ACL) reconstruction?
AB - BACKGROUND: Approximately 100,000 anterior cruciate ligament (ACL)
reconstructions are performed in the USA each year. Interference screw fixation
is considered the standard for rigid fixation of the graft and provides higher
fixation strength compared with other devices such as staples or buttons. The
present study summarizes the latest evidence comparing the effectiveness of the
available classes of interference screws for fixation of ACL grafts. SOURCES: A
comprehensive search of the CINAHL, PubMed, Google Scholar, Embase Biomedical
databases and the Cochrane Central Registry of Controlled Trials was performed in
March 2013. Twelve studies met our inclusion criteria. AREAS OF AGREEMENT: Most
studies showed no intergroup difference in terms of outcomes measured with
validated clinical scores such as IKDC (International Knee Documentation
Committee), Lysholm score and Tegner activity level. There was no significant
difference regarding range of motion. Knee stability as evaluated with pivot
shift and KT arthrometer showed a significant difference only in one study,
favouring metallic interference screws. Tunnel widening is much more evident and
marked patients who underwent ACL reconstruction with bioabsorbable screws, with
no influence on the final clinical results achieved. Complication rates between
the two screw classes were similar. The average modified Coleman methodology
score was 74.67. AREAS OF UNCERTAINTY/RESEARCH NEED: The data comparing the
outcomes achieved by two different materials for fixation, bioabsorbable and
metallic, to be used during single-bundle ACL reconstruction, showed no
significant difference in the final patient outcomes, in terms of clinical
scores, clinical evaluation and imaging.
PMID- 24357732
TI - Maternal supervision of children during their first 3 years of life: the
influence of maternal depression and child gender.
AB - OBJECTIVE: The present study examined the effect of child gender and maternal
depressive symptoms on routine supervisory practices of mothers longitudinally.
METHOD: Self-report supervision practices were obtained at various time points
from 3 months through 3 years of age. RESULTS: From 3 to 36 months, the quantity
of time mothers reported supervising decreased from 7.1 to 6.3 hours, and the
proportion of time spent in an intense style decreased from 63 to 46%, whereas
that spent in a peripheral style increased from 14 to 32%. Mothers reported more
time supervising girls and a greater proportion of this was in an intense style.
Mothers with elevated depressive symptoms reported more time supervising but a
lower proportion in an intense style. CONCLUSION: Over the first 36 months of
life, routine patterns of supervision change and these vary as a function of
maternal depression symptoms and child gender. Implications for child injury risk
are discussed.
PMID- 24357734
TI - Implementing tissue engineering and regenerative medicine solutions in medical
implants.
AB - BACKGROUND: Surgical implants are widely used in the medical field but their long
term performance is limited due to failure of integration with tissues. This
manuscript describes very well-known problems associated with implants and
discusses novel solutions used in tissue engineering and regenerative medicine
that can be implemented in this uncommonly discussed medical area. SOURCES OF
DATA: General and medical literature describing modifications of medical and
surgical implants, biofunctionalization, tissue engineering and regenerative
medicine. AREAS OF AGREEMENT: Procedures for surgical implantation have grown
substantially in the last few decades and provided improved quality of life for
patients, regardless of area of implantation and device type and purpose. AREAS
OF CONTROVERSY: In general, implants fail because of lack of long-term
integration with the surrounding tissues. Implant manufacturers have not
addressed implant failure from the point of view of biointegration. In addition,
some medical practitioners are inclined to treat implant failure by using anti
infection methods to prevent bacterial adhesion. However, both approaches are
conceptually limited, as discussed in this manuscript. GROWING POINTS:
Implantation in the future will not be limited to medically needed procedures but
also to a growing number of cosmetic body transformation procedures, which may
include perceived 'improved implant functions' over natural tissues or organs. An
additional trend is that implant procedures are being progressively performed in
younger individuals. AREAS TIMELY FOR DEVELOPING RESEARCH: Current implants
generally do not allow the physician to have controlled long-term access to
internal tissues in contact with the implants, for example to release specific
compounds when medically needed to the problem area.
PMID- 24357735
TI - Thoracic inspirations: advances in the diagnosis, staging, and treatment of non
small-cell lung cancer.
PMID- 24357737
TI - Minimally invasive mediastinal staging of non-small-cell lung cancer: emphasis on
ultrasonography-guided fine-needle aspiration.
AB - BACKGROUND: Mediastinal staging in patients with non-small-cell lung cancer
(NSCLC) is crucial in dictating surgical vs nonsurgical treatment. Cervical
mediastinoscopy is the "gold standard" in mediastinal staging but is invasive and
limited in assessing the posterior subcarinal, lower mediastinal, and hilar lymph
nodes. Less invasive approaches to NSCLC staging have become more widely
available. METHODS: This article reviews several of these techniques, including
noninvasive mediastinal staging of NSCLC, endobronchial ultrasound (EBUS) and
fine-needle aspiration (FNA), endoscopic ultrasound (EUS) and FNA, and the
combination of EBUS/EUS. RESULTS: Noninvasive mediastinal staging with computed
tomography and positron-emission tomography scans has significant false-negative
and false-positive rates and requires lymph node tissue confirmation. FNA
techniques, with guidance by EBUS and EUS, have become more widely available. The
combination of EBUS-FNA and EUS-FNA of mediastinal lymph nodes can be a viable
alternative to surgical mediastinal staging. Current barriers to the
dissemination of these techniques include initial cost of equipment, lack of
access to rapid on-site cytology, and the time required to obtain sufficient
skills to duplicate published results. CONCLUSIONS: Within the last decade, these
approaches to NSCLC staging have become more widely available. Continued study
into these noninvasive techniques is warranted.
PMID- 24357736
TI - Lung cancer screening: advantages, controversies, and applications.
AB - BACKGROUND: Lung cancer is the leading cause of cancer death in the United
States. Results from the National Lung Screening Trial (NLST) have shown that low
dose computed tomography (CT) is capable of detecting lung neoplasms in
individuals at high risk. However, whether it is advantageous to perform lung
cancer screening on these patients is a significant concern, as are the potential
adverse outcomes from screening. METHODS: A review of several randomized clinical
trials, focusing on the NLST, was undertaken. Adverse outcomes and costs related
to lung cancer screening were also examined. RESULTS: Lung cancer screening using
low-dose CT in high-risk individuals reduced lung cancer deaths by more than 20%
when compared with those screened by chest radiography. False-positive results
were seen in both groups, but the number of adverse events from the screening
test and subsequent diagnostic procedures was low. CONCLUSIONS: Lung cancer
screening is controversial, but the NLST has demonstrated that such testing may
reduce lung cancer deaths in high-risk individuals when performed with low-dose
CT rather than chest radiography. Guidelines should be established to not only
help identify an appropriate screening population, but also develop standards for
radiological testing.
PMID- 24357738
TI - Systemic and targeted therapies for early-stage lung cancer.
AB - BACKGROUND: Even with aggressive surgical treatment, relapse rates remain high
for patients with resectable non-small-cell lung cancer (NSCLC). In an effort to
improve survival in these patients, numerous clinical trials have evaluated
neoadjuvant and adjuvant chemotherapy. METHODS: The authors reviewed the results
of the prospective randomized clinical trials that have established adjuvant
chemotherapy as the standard of care for patients with surgically resected NSCLC.
In addition, the authors summarize data on predictive and prognostic markers for
patients with early-stage NSCLC and discuss novel therapies and clinical trials
currently underway in early-stage NSCLC. RESULTS: Three large randomized clinical
trials and two meta-analyses have demonstrated a survival benefit for adjuvant
cisplatin-based chemotherapy compared with surgery alone in patients with early
stage NSCLC. As a result, adjuvant cisplatin-based chemotherapy is recommended as
the standard of care in these patients. Numerous promising biomarkers and agents
have been developed in the metastatic setting and are currently being evaluated
in the adjuvant setting. CONCLUSIONS: While adjuvant chemotherapy has improved
survival for patients with early-stage NSCLC, the prognosis for early-stage lung
cancer remains poor. Incorporation of molecular markers and targeted therapies
into the management of patients with advanced NSCLC has improved outcomes.
Development of these strategies in the adjuvant setting offers the potential to
increase cure rates in patients with early-stage NSCLC.
PMID- 24357739
TI - Current clinical application of genomic and proteomic profiling in non-small-cell
lung cancer.
AB - BACKGROUND: Genomic or proteomic profiling of cancer can be broadly defined as a
systematic grouping of cancer based on its genetic or protein makeup. In the
management of non-small-cell lung cancer (NSCLC), genomic and proteomic profiling
applications have become useful in early disease detection, diagnosis, treatment,
and prognostication. METHODS: We reviewed the recent literature on the
applications of genomic and proteomic profiling in NSCLC. Important applications
were summarized into those already adopted as standard care and those still under
investigation. RESULTS: For genomic profiling, testing for EGFR mutation and ALK
rearrangement has become routine for adenocarcinoma. Multiplex assay and
malignancy-risk gene signature are both important applications in development. A
test to predict outcome after treatment with an epidermal growth factor
rector/tyrosine kinase inhibitor and a screening blood test for lung cancer are
being investigated for use in proteomic profiling. CONCLUSIONS: Genomic profiling
is routine in patients with NSCLC, and proteomic profiling shows promise.
Additional genomic and proteomic profiling applications may also prove to be
useful contributions in the care of these patients.
PMID- 24357740
TI - Survivorship issues for patients with lung cancer.
AB - BACKGROUND: Survivorship concerns for patients with lung and bronchus cancers
include quality of life and physical and psychological aspects. Recommendations
for follow-up care should incorporate a survivorship paradigm and practices for
these patients. METHODS: The authors conducted a literature review on lung cancer
survivorship and the late- and long-term effects of treatment, which can impair
quality of life in this patient population. RESULTS: Lung cancer is a diagnosis
associated with heavy disease burden, and patients may benefit from survivorship
care. High levels of physical and psychological distress leading to diminished
quality of life are common in those with lung cancer. Recognition of the
potential late- and long-term effects of treatment may help health care
professionals intervene early to minimize negative implications. CONCLUSIONS:
Survivorship care for patients with cancer requires a multidisciplinary effort
and team approach. Addressing the survivorship needs of these patients and their
caregivers, along with providing a continuum of cancer care, should improve their
quality of life. Further research on evidence-based practices on the long-term
effects of lung cancer survivorship care is necessary.
PMID- 24357741
TI - Temporal trends in demographics and overall survival of non-small-cell lung
cancer patients at Moffitt Cancer Center from 1986 to 2008.
AB - BACKGROUND: An assessment of historical trends in patient survival is important
to determine the progress toward patient outcomes and to reveal where
advancements must be made. The goal of this study was to assess changes in
demographics and overall survival of non-small-cell lung cancer (NSCLC) patients
who were seen at Moffitt Cancer Center spanning 22 years. METHODS: This analysis
included 4,997 NSCLC patients who were treated at our institute over 5 time
periods: 1986 to 1988, 1991 to 1993, 1996 to 1998, 2001 to 2003, and 2006 to
2008. Kaplan-Meier survival curves and the log-rank statistic were used to assess
changes in 5-year survival rates over the 5 time periods, and multivariable
hazard ratios were estimated from Cox proportional hazards models. RESULTS: From
1986 to 2008 we observed statistically significant increases in the percentage of
patients over the age of 70 years, women, never-smokers and former smokers, and
patients with stage I tumors. Over the same time period the median survival time
statistically significantly increased from 1.09 years (95% confidence interval
[CI], 0.95-1.34, P < .001) to 2.27 years (95% CI, 2.07-2.46, P < .001), and the
overall 5-year survival rate for all patients significantly increased from 14.7%
to 31.1% (P < .001). Among stage I patients, the 5-year survival rate increased
from 31.7% to 54.0% (P < .001), 13.3% to 36.0% for stage II (P < .001), 10.5% to
21.7% for stage III (P < .001), and 3.4% to 9.6% for stage IV (P < .001).
CONCLUSIONS: This analysis demonstrated important temporal changes in the
demographics and improvements in overall survival of NSCLC patients treated at
our institute from 1986 to 2008. The 5-year survival rates and median survival
time of patients diagnosed with NSCLC has significantly improved across all
stages, including patients with late-stage disease.
PMID- 24357742
TI - Multidisciplinary therapy of stage IIIA non-small-cell lung cancer: long-term
outcome of chemoradiation with or without surgery.
AB - BACKGROUND: Stage IIIA non-small-cell lung cancer (NSCLC) is highly heterogeneous
due to differences in the size of the primary tumor and the extent and location
of nodal disease. Although the addition of surgery to chemoradiation did not
improve overall survival (OS) for stage IIIA patients in a randomized intergroup
trial (INT 0139), subset analyses of the trial suggest that a trimodality
approach incorporating lobectomy may be superior to bimodality therapy with
chemoradiation alone. METHODS: We analyzed the outcomes of patients with stage
IIIA NSCLC (T3N1, T1-3N2) treated at our center between January 2000 and December
2008. We compared OS for those undergoing definitive chemoradiation to those
undergoing chemoradiation followed by either lobectomy or pneumonectomy.
Demographic variables were balanced by propensity score analysis method. RESULTS:
In our analysis of 249 patients, the median age was 65 years, 43% were men, and
96.5% had N2 disease. Chemoradiation followed by lobectomy yielded superior OS
compared with chemoradiation (median OS 39 months vs 22 months, P = .038 after
propensity score adjustment). There was no significant survival benefit for
pneumonectomy over chemoradiation (median survival 28 months vs 22 months, P =
.534). CONCLUSIONS: Our data corroborate the findings of the INT 0139 trial. We
propose that a formal randomized trial be performed comparing chemoradiation
followed by lobectomy vs definitive chemoradiation in patients with stage IIIA
disease whose tumors are resectable by lobectomy. Our data do not support the
incorporation of pneumonectomy in the management of stage IIIA patients with N2
disease.
PMID- 24357743
TI - Incidence and outcomes of chemotherapy and radiation in morbidly obese patients
with locally advanced lung and esophageal cancers: a single-institution
experience.
AB - BACKGROUND: In 2012, the American Society of Clinical Oncology issued a guideline
urging health care professionals to "routinely use an obese patient's actual body
weight, rather than an ideal body weight or other estimate, to calculate the
appropriate dose of nearly all chemotherapy drugs. " This guideline does not
address dosages for patients who are morbidly obese (body mass index >= 40) and
receiving concomitant chemotherapy and radiation. METHODS: This report describes
a single-institution experience intended to address the issue of appropriate
dosages for this patient population. RESULTS: Among 1,886 cancer patients who
received curative thoracic radiation at the Mayo Clinic, 16 (0.8%) were morbidly
obese and received concomitant chemotherapy and radiation. Charlson morbidity
scores for the cohort ranged from 2 to 9, and 10 patients had esophageal cancer.
Ten of 16 patients received an initial chemotherapy dose reduction, and 4 of
these patients experienced major adverse events, including 1 death. Similarly,
among the 6 patients who received full-dose chemotherapy at the beginning of
treatment, 2 had major adverse events. Nine patients went on to have their
cancers resected, but no differences in survival were apparent among patients who
received initial dose reductions and those who did not. CONCLUSIONS: This single
institution experience remains limited. However, in view of the severe toxicity
observed in this cohort, chemotherapy dose reductions seem appropriate in
specific instances. Clinicians should also consider prescribing newer
chemotherapy regimens that may be better tolerated in morbidly obese patients
with cancer.
PMID- 24357744
TI - Advanced EGFR mutation-positive non-small-cell lung cancer: case report,
literature review, and treatment recommendations.
AB - BACKGROUND: Lung cancer is the leading cause of cancer mortality. Non-small-cell
lung cancer (NSCLC) comprises up to 90% of all lung cancers. Conventional
treatment for advanced NSCLC consists of chemotherapy and has a small impact on
survival. Molecular targets, such as epidermal growth factor receptor (EGFR),
involved in cell signaling have led to the development of new, targeted therapies
over the past 15 years. METHODS: Using a case report from our clinical practice,
we review the literature and provide guidelines to the approach and management of
advanced EGFR mutation-positive NSCLC. RESULTS: Targeted and/or biologic (small
molecules or monoclonal antibodies) cancer therapies have vaulted to the
forefront of clinical research and therapeutic use. Our recommendation, backed by
strong scientific evidence, is to treat patients with advanced or recurrent NSCLC
harboring activating EGFR mutation with an EGFR tyrosine kinase inhibitor (TKI)
as early as possible. Erlotinib is currently the drug of choice in the United
States, although afatinib, due to its recent approval by the US Food and Drug
Administration, will soon be available. CONCLUSIONS: Improved understanding of
cell signaling pathways that control cellular proliferation, differentiation, and
survival combined with our increased ability to screen for specific mutations
that drive malignant transformation and oncogenic behavior, has altered our
treatment of advanced NSCLC. We can now provide a more individualized approach
associated with improved progression-free survival and quality of life.
PMID- 24357745
TI - Epidermal growth factor receptor inhibitors: coming of age.
AB - BACKGROUND: Agents targeting the epidermal growth factor (EGFR)-mediated
signaling pathway are used in the treatment of various solid tumors, including
lung, breast, pancreatic, colorectal, and head and neck cancers. METHODS:
Clinical evidence supporting the benefits of targeted agents directed against
EGFR/HER1 in various solid tumors is discussed, as well as the survival end
points used in the pivotal clinical trials, current applications, and future
research directions. Agents reviewed include the monoclonal antibodies cetuximab
and panitumumab, both of which block ligand binding to the extracellular domain,
and the small-molecule tyrosine kinase inhibitors gefitinib, erlotinib, and
afatinib that exert their effects at the intracellular portion of the receptor to
prevent tyrosine kinase phosphorylation and the activation of signal transduction
pathways. RESULTS: EGFR inhibitors have a mechanism of action distinct from
traditional cytotoxic therapies, and combining these agents with chemotherapy
produces synergistic anticancer activity without overlapping toxicity profiles.
The level of EGFR expression does not correlate with agent response, and many
tumors are resistant to treatment. Even if tumors are initially sensitive to
these agents, they inevitably acquire resistance through complex, poorly
understood molecular mechanisms. CONCLUSIONS: EGFR-directed therapies have
changed the treatment paradigms in metastatic lung, colorectal, and head and neck
cancers and improved outcomes. A better understanding of mechanisms of resistance
to these agents is crucial for effective drug development. Predictive biomarkers
are being developed to deliver personalized therapies.
PMID- 24357746
TI - Update on immune checkpoint inhibitors in lung cancer.
AB - BACKGROUND: The immune checkpoint proteins, including the B7/CD28 receptor
superfamily, have become increasingly important targets for pharmacologic
blockade. Several classes of new agents have impressive clinical activity, and
their eventual approval for treatment of lung cancer seems likely. METHODS: This
article discusses the current development of these agents, including the CTLA-4,
PD-1, and PD-L1 inhibitory pathways, killer immunoglobulin receptor (KIR )
inhibition, and other checkpoint proteins. RESULTS: Ipilimumab in combination
with chemotherapy has exhibited encouraging results in small-cell and non-small
cell lung cancer alike. Reported phase I trials of the monoclonal antibodies
nivolumab, MK-3475, MEDI4736, and MPDL3280A are demonstrating durable overall
radiological response rates in the 20% to 25% range in lung cancer. This
exceptional activity includes squamous lung cancers, a population historically
bereft of significant therapeutic advances. Retrospective examination of tumor PD
L1 expression suggests that PD-L1 may eventually be evaluable as a predictive
biomarker. Dual checkpoint blockade strategies, such as those combining anti-CTLA
4, anti-LAG-3, or anti-KIR, are being tested to increase the proportion and
durability of tumor responses. Examination of acquired immune resistance and post
immunotherapy relapse strategies are underway. CONCLUSIONS: These emerging
antibodies hold great potential for the systemic control of epithelial cancers
such as lung cancer.
PMID- 24357747
TI - Quality of care of patients with non-small-cell lung cancer: a report of a
performance improvement initiative.
AB - BACKGROUND: Lung cancer is the leading cause of cancer deaths in the United
States. In recent years, significant advancements have been made in the molecular
characterization of tumors, and the availability of new agents to treat non-small
cell lung cancer has increased. Despite these achievements, optimal care of
patients with this condition remains less than ideal. Although national quality
measures and guideline recommendations provide the necessary framework for
patient care, routine self-assessment of adherence to these measures is required
for physician practice improvement. To this end, a performance improvement
initiative that met national continuing medical education standards was designed.
METHODS: Focusing on non-small-cell lung cancer patient care, oncologists
underwent a three-step process that included a self-assessment of predetermined
performance measures, the development and implementation of an actionable plan
for improvement, and a second round of assessment to measure practice change.
RESULTS: A total of 440 unique patient charts were reviewed by 22 practicing
oncologists. Participants demonstrated high baseline performance levels of
established quality measures, such as inclusion of the patient's pathology report
and assessment of smoking history. Significant gains were observed in the areas
of supportive care, including assessment of the patient's emotional well-being
and the use of molecular markers in diagnostic and treatment decision making.
CONCLUSIONS: Data from this study support the value of performance improvement
initiatives to help increase physician delivery of evidence-based care to
patients.
PMID- 24357748
TI - A comparison of the IED-related eye injury rate in ANSF and ISAF forces at the UK
R3 Hospital, Camp Bastion, 2013.
PMID- 24357749
TI - Taking flight.
PMID- 24357750
TI - Treatment consent.
PMID- 24357751
TI - A warning from the past.
PMID- 24357752
TI - Symptom prescription.
PMID- 24357753
TI - Exuberant hypercementosis.
PMID- 24357754
TI - It's been said, stupid.
PMID- 24357756
TI - Leading speakers secured for Manchester.
PMID- 24357757
TI - Gum disease increases asthma risk.
PMID- 24357758
TI - Help slow the global growth of antibiotic resistance.
PMID- 24357762
TI - Dentists encouraged to support fostered children.
PMID- 24357763
TI - Direct access: lessons learnt from the Netherlands.
AB - OBJECTIVE: To use a qualitative approach to examine the perceptions of policy
makers, general dental practitioners, dental hygienists, dental students and
dental hygiene students in the Netherlands following the introduction of a direct
access policy in 2006. METHODS: Semi-structured interviews and focus groups were
undertaken with a variety of policy makers and clinicians in the Netherlands.
These were recorded and transcribed verbatim into MS Word documents. The
transcripts were line numbered and subjected to thematic analysis to develop a
coding frame using NVivo. RESULTS: Four main themes are reported, which represent
a subset of a policy analysis of direct access in the Netherlands. These were
entitled: 'The narrative of implementation', 'Working models of direct access',
'Relationship between old- and new-style hygienists' and 'Public attitudes'.
CONCLUSIONS: Working relationships within integrated practices in the Netherlands
are positive, but attitudes towards independent practice are mixed. Good examples
of collaborative working across practices were observed, but relationships
between the professional bodies remain difficult seven years on since the
introduction of the policy.
PMID- 24357764
TI - Do general dental practitioners leave teeth on 'open drainage'?
AB - OBJECTIVE: There is a need to ascertain the use of evidence-based dentistry in
both primary and secondary care in order to tailor education. This study aims to
evaluate the use of 'open drainage' as part of endodontic treatment in primary
care in South Yorkshire. METHODS: A questionnaire was circulated to 141 randomly
selected general dental practitioners in the South Yorkshire area between January
2012 and January 2013. RESULTS: The response rate was 79% (112/141). Five of the
returned questionnaires were incomplete and therefore not usable. Seventy-nine
percent of respondents were general dental practitioners (GDPs) working in mainly
NHS or mixed practices. The year of graduation varied between 1970 and 2011.
Forty-one percent (44/107) stated that they had never left a tooth on open
drainage. Twenty-nine percent (31/107) stated that they sometimes leave teeth on
open drainage. Of those respondents who currently leave teeth on open drainage,
most (68%) would leave teeth on open drainage for one to two days or less.
CONCLUSIONS: This survey revealed that the practice of leaving teeth on open
drainage is still present in general dental practice. Current guidelines do not
comment on the use of this treatment modality. There is a need to ascertain
further information about practices throughout the United Kingdom in order to
provide clear evidence-based guidelines.
PMID- 24357765
TI - An observational study to assess the association between osteoporosis and
periodontal disease.
AB - BACKGROUND: There is evidence to suggest osteoporosis may result in premature
tooth loss. The pathology behind this relationship is poorly understood. A
correlation with osteoporosis and greater susceptibility to periodontal disease
has been suggested. OBJECTIVES: To investigate the association between
osteoporosis and periodontal disease, accounting for the effect of confounding
variables of age, smoking status and oral hygiene.Setting Three hundred and fifty
nine postmenopausal women aged 45-70 years were recruited from the Greater
Manchester area between March 2008 and June 2010.Subjects and methods Data were
collected on osteoporosis status, smoking status, pocket probing depths,
suppuration, plaque, bleeding and calculus indices. Dental panoramic tomographs
were taken and periodontal bone support assessed on all teeth. Data were analysed
using SPSS software (version 20). RESULTS: Complete data were available for 348
patients. Twenty-six percent (91) of individuals were osteoporotic. Logistic
regression was used. The relationship between osteoporosis status and moderate to
severe periodontal disease of both molar teeth and the whole mouth was not
significant (p = 0.088 and p = 0.296 respectively). CONCLUSIONS: Osteoporosis is
not a causal factor in the development of moderate to severe chronic
periodontitis.
PMID- 24357792
TI - Liverpool care pathway was made a scapegoat, says palliative care consultant.
PMID- 24357793
TI - Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene
among petroleum workers.
AB - BACKGROUND: High benzene exposure causes acute myeloid leukaemia (AML). Three
petroleum case-control studies identified 60 cases (241 matched controls) for AML
and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL).
METHODS: Cases were classified and scored regarding uncertainty by two
haematologists using available diagnostic information. Blinded quantitative
benzene exposure assessment used work histories and exposure measurements
adjusted for era-specific circumstances. Statistical analyses included
conditional logistic regression and penalised smoothing splines. RESULTS: Benzene
exposures were much lower than previous studies. Categorical analyses showed
increased ORs for AML with several exposure metrics, although patterns were
unclear; neither continuous exposure metrics nor spline analyses gave increased
risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No
relationship was found between benzene exposure and risk of CLL, although the
Australian study showed increased risks in refinery workers. CONCLUSION: Overall,
this study does not persuasively demonstrate a risk between benzene and AML. A
previously reported strong relationship between myelodysplastic syndrome (MDS)
(potentially previously reported as AML) at our study's low benzene levels
suggests that MDS may be the more relevant health risk for lower exposure. Higher
CLL risks in refinery workers may be due to more diverse exposures than benzene
alone.
PMID- 24357794
TI - The derived neutrophil to lymphocyte ratio is an independent prognostic factor in
patients with diffuse large B-cell lymphoma.
AB - BACKGROUND: With growing evidence on the role of inflammation in cancer biology,
the systemic inflammatory response has been postulated as having prognostic
significance in a wide range of different cancer types. Recently, the derived
neutrophil to lymphocyte ratio (dNLR) has been proposed as an easily determinable
prognostic factor in cancer patients. Nevertheless, its prognostic significance
in diffuse large B-cell lymphoma (DLBCL) patients has never been explored.
METHODS: Data from 290 consecutive DLBCL patients, diagnosed between 2004 and
2013 at a single Austrian centre, were evaluated retrospectively. The prognostic
influence of the dNLR and other clinico-pathological factors including age,
lactate dehydrogenase, cell of origin category and Ann Arbor stage on 5-year
overall- (OS) and disease-free (DFS) survival was studied by Kaplan-Meier curves.
To evaluate the independent prognostic relevance of dNLR, univariate and
multivariate Cox regression models were applied. RESULTS: An independent
significant association between high dNLR and poor clinical outcome in
multivariate analysis for OS (HR=2.02, confidence interval (CI) 95%=1.17-3.50,
P=0.011), as well as DFS (HR=2.15, CI 95%=1.04-4.47, P=0.038), was identified.
CONCLUSION: In the present study, we showed that a high dNLR at diagnosis of
DLBCL represents an independent poor prognostic factor for clinical outcome. Our
data encourage the further validation of this easily available parameter in
prospective studies and as a potential stratification tool in clinical trials.
PMID- 24357795
TI - Endothelin B receptor expression correlates with tumour angiogenesis and
prognosis in oesophageal squamous cell carcinoma.
AB - BACKGROUND: The endothelin axis has been shown to have a pivotal role in several
human malignancies. The aim of this study was to clarify the clinical importance
of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma
(OSCC). METHODS: We evaluated ETBR expression in 107 patients with OSCC by
immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were
assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8,
and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically
analysed. RESULTS: Sixty-one (57%) cases showed high expression of ETBR.
Endothelin receptor type B expression was correlated with several
clinicopathological factors including tumour differentiation, tumour depth, and
lymph node metastasis. The overall and disease-specific survival rates were
significantly lower in patients with high ETBR expression than patients with low
expression. Furthermore, multivariate analysis revealed that ETBR status was an
independent prognostic factor for patient survival. Mechanistic analysis
indicated that MVD was significantly higher in tumour tissues with high ETBR
expression compared with those with low expression, suggesting that angiogenesis
may be a key mechanism in tumour progression and metastasis of OSCC mediated by
ETBR expression. By contrast, there were no significant correlations between TILs
and ETBR expression. CONCLUSION: Endothelin receptor type B has a pivotal role in
oesophageal cancer and may be therapeutic target for this intractable malignancy.
PMID- 24357796
TI - The preoperative lymphocyte to monocyte ratio predicts clinical outcome in
patients with stage III colon cancer.
AB - BACKGROUND: Inflammation has a critical role in the pathogenesis and progression
of cancer. The lymphocyte to monocyte ratio (LMR) could be shown to be prognostic
in haematologic neoplasia. In this study, we analysed the LMR with clinical
outcome in stage II and III colon cancer patients. METHODS: Three hundred and
seventy-two patients with stage II and III colon cancer were included in this
retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses
were calculated for time to recurrence (TTR) and overall survival (OS). RESULTS:
Including all patients, the elevated preoperative LMR was significantly
associated with increased TTR and OS in multivariate analysis (HR: 0.47, 95%CI:
0.29-0.76, P=0.002; HR: 0.51, 95%CI: 0.31-0.83, P=0.007; respectively). In
subanalyses, the association was limited to patients with stage III (HR: 0.40,
95%CI: 0.22-0.72, P=0.002), in contrast to patients with stage II (HR: 0.40,
95%CI: 0.28-1.66, P=0.397). When the subgroup of patients with 'high-risk'
LMR<=2.83 was analysed, no benefit of adjuvant 5-FU-based chemotherapy could be
found (HR: 0.99; 95%CI: 0.60-1.63; P=0.953). CONCLUSION: The LMR might be an
independent prognostic marker for TTR in stage III colon cancer patients. Our
results further suggest that high-risk patients based on the LMR do not benefit
from adjuvant chemotherapy. Independent validation of our findings is warranted.
PMID- 24357797
TI - IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is
regulated by promoter DNA methylation.
AB - BACKGROUND: We examined whether silencing of IGFBP7 was associated with survival
in patients with oesophageal adenocarcinoma. METHODS: Protein expression of
IGFBP7 was determined using immunohistochemistry in a tissue microarray
representing tumours from 65 patients with oesophageal adenocarcinoma who had not
had neoadjuvant therapy. DNA methylation of the IGFBP7 promoter was determined
with the melt curve analysis in cell lines and patient tissues. RESULTS:
Expression of IGFBP7 was observed in the oesophageal adenocarcinoma of 34 out of
65 (52%) patients and was associated with significantly reduced median (11 vs 92
months) and 5-year survival (25% vs 52%). Multivariate analysis identified
expression as an independent prognostic indicator for survival (hazard
ratio=3.24, 95% confidence interval=1.58-6.67, P-value=0.0014). Hypermethylation
of IGFBP7 was associated with silencing of gene expression in cell lines and
patient tissues (P-value=0.0225). Methylation was observed in the squamous mucosa
of 2 out of 15 (13%) patients with Barrett's oesophagus and 3 out of 17 (18%)
with oesophageal adenocarcinoma. Methylation was observed in 14 out of 18 (78%)
of biopsies of Barrett's mucosa and 23 out of 34 (68%) patients with oesophageal
adenocarcinoma. CONCLUSION: Reduced IGFBP7 protein expression was associated with
longer survival in patients with oesophageal adenocarcinoma. Methylation of the
IGFBP7 promoter was associated with silencing of gene expression and was frequent
in Barrett's oesophagus and oesophageal adenocarcinoma.
PMID- 24357798
TI - Intermediate-risk grouping of cervical cancer patients treated with radical
hysterectomy: a Korean Gynecologic Oncology Group study.
AB - BACKGROUND: In this study, we sought to identify a criterion for the intermediate
risk grouping of patients with cervical cancer who exhibit any intermediate-risk
factor after radical hysterectomy. METHODS: In total, 2158 patients with
pathologically proven stage IB-IIA cervical cancer with any intermediate-risk
factor after radical hysterectomy were randomly assigned to two groups, a
development group and a validation group, at a ratio of 3 : 1 (1620 patients:538
patients). To predict recurrence, multivariate models were developed using the
development group. The ability of the models to discriminate between groups was
validated using the log-rank test and receiver operating characteristic (ROC)
analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion
(DSI), and lymphovascular space involvement (LVSI)) were significantly associated
with disease recurrence and included in the models. Among the nine possible
combinations of the four variables, models consisting of any two of the four
intermediate-risk factors (tumour size >=3 cm, DSI of the outer third of the
cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology)
demonstrated the best performance for predicting recurrence. CONCLUSION: This
study identified a 'four-factor model' in which the presence of any two factors
may be useful for predicting recurrence in patients with cervical cancer treated
with radical hysterectomy.
PMID- 24357799
TI - ERO1alpha-dependent endoplasmic reticulum-mitochondrial calcium flux contributes
to ER stress and mitochondrial permeabilization by procaspase-activating compound
1 (PAC-1).
AB - Procaspase-activating compound-1 (PAC-1) is the first direct caspase-activating
compound discovered; using an in vitro cell-free system of caspase activation.
Subsequently, this compound was shown to induce apoptosis in a variety of cancer
cells with promising in vivo antitumor activity in canine lymphoma model.
Recently, we have reported its ability to kill drug-resistant, Bcl-2/Bcl-xL
overexpressing and Bax/Bak-deficient cells despite the essential requirement of
mitochondrial cytochrome c (cyt. c) release for caspase activation, indicating
that the key molecular targets of PAC-1 in cancer cells are yet to be identified.
Here, we have identified Ero1alpha-dependent endoplasmic reticulum (ER) calcium
leakage to mitochondria through mitochondria-associated ER membranes (MAM) and ER
luminal hyper-oxidation as the critical events of PAC-1-mediated cell death. PAC
1 treatment upregulated Ero1alpha in multiple cell lines, whereas silencing of
Ero1alpha significantly inhibited calcium release from ER and cell death. Loss of
ER calcium and hyper-oxidation of ER lumen by Ero1alpha collectively triggered ER
stress. Upregulation of GRP78 and splicing of X-box-binding protein 1 (XBP1) mRNA
in multiple cancer cells suggested ER stress as the general event triggered by
PAC-1. XBP1 mRNA splicing and GRP78 upregulation confirmed ER stress even in
Bax/Bak double knockout and PAC-1-resistant Apaf-1-knockout cells, indicating an
induction of ER stress-mediated mitochondrial apoptosis by PAC-1. Furthermore, we
identified BH3-only protein p53 upregulated modulator of apoptosis (PUMA) as the
key molecular link that orchestrates overwhelmed ER stress to mitochondria
mediated apoptosis, involving mitochondrial reactive oxygen species, in a p53
independent manner. Silencing of PUMA in cancer cells effectively reduced cyt. c
release and cell death by PAC-1.
PMID- 24357800
TI - Chloride channels are necessary for full platelet phosphatidylserine exposure and
procoagulant activity.
AB - Platelets enhance thrombin generation at sites of vascular injury by exposing
phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is
required for Ca(2+)-dependent phosphatidylserine exposure and is defective in
patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-)
channels, though the role of Cl(-) fluxes in platelet procoagulant activity has
not been explored. We found that Cl(-) channel blockers or removal of
extracellular Cl(-) inhibited agonist-induced phosphatidylserine exposure.
However, this was not due to direct inhibition of Ca(2+)-dependent scrambling
since Ca(2+) ionophore-induced phosphatidylserine exposure was normal. This
implies that the role of Ano6 in Ca(2+-)dependent PS exposure is likely to differ
from any putative function of Ano6 as a Cl(-) channel. Instead, Cl(-) channel
blockade inhibited agonist-induced Ca(2+) entry. Importantly, Cl(-) channel
blockers also prevented agonist-induced membrane hyperpolarization, resulting in
depolarization. We propose that Cl(-) entry through Cl(-) channels is required
for this hyperpolarization, maintaining the driving force for Ca(2+) entry and
triggering full phosphatidylserine exposure. This demonstrates a novel role for
Cl(-) channels in controlling platelet death and procoagulant activity.
PMID- 24357801
TI - In serum veritas-in serum sanitas? Cell non-autonomous aging compromises
differentiation and survival of mesenchymal stromal cells via the oxidative
stress pathway.
AB - Even tissues capable of complete regeneration, such as bone, show an age-related
reduction in their healing capacity. Here, we hypothesized that this decline is
primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic
environment. We demonstrate that culture of mesenchymal stromal cells (MSCs) in
serum from aged Sprague-Dawley rats negatively affects their survival and
differentiation ability. Proteome analysis and further cellular investigations
strongly suggest that serum from aged animals not only changes expression of
proteins related to mitochondria, unfolded protein binding or involved in stress
responses, it also significantly enhances intracellular reactive oxygen species
production and leads to the accumulation of oxidatively damaged proteins.
Conversely, reduction of oxidative stress levels in vitro markedly improved MSC
function. These results were validated in an in vivo model of compromised bone
healing, which demonstrated significant increase regeneration in aged animals
following oral antioxidant administration. These observations indicate the high
impact of extrinsic aging on cellular functions and the process of endogenous
(bone) regeneration. Thus, addressing the cell environment by, for example,
systemic antioxidant treatment is a promising approach to enhance tissue
regeneration and to regain cellular function especially in elderly patients.
PMID- 24357802
TI - Turning up the heat: heat stress induces markers of programmed cell death in
Plasmodium falciparum in vitro.
AB - Malaria is characterised by cyclical febrile episodes that result from the
rupture of mature schizont-infected erythrocytes releasing merozoites. In
patients infected with Plasmodium falciparum, fever may reach peak temperatures
as high as 41 degrees C. Febrile episodes typically have a deleterious effect on
parasites and probably benefit the host by aiding parasite clearance; however,
the parasite may also gain advantage from limiting its burden on the host and
prolonging infection to ensure development and transmission of slow-maturing
gametocytes. Programmed cell death (PCD) may provide the parasite with a
mechanism of self-limitation, although the occurrence and phenotype of PCD in the
erythrocytic stages remain controversial due to conflicting data. This study
aimed to characterise the cell death phenotype of P. falciparum in response to in
vitro heat stress. A variety of biochemical markers of PCD, including DNA
fragmentation, mitochondrial dysregulation and phosphatidylserine
externalisation, as well as morphological studies of Giemsa-stained thin smears
and real-time microscopy were utilised to characterise the phenotype. Heat stress
decreased P. falciparum growth and development in vitro. Late-stage parasites
were more susceptible, although early stages were more affected than expected.
Early-stage parasites exposed to 41 degrees C exhibited markers of an apoptosis
like PCD phenotype, including DNA fragmentation and mitochondrial depolarisation.
Heat-stressed late-stage parasites showed no significant DNA fragmentation or
mitochondrial dysregulation; however, cytoplasmic vacuolisation was suggestive of
an autophagy-like form of PCD. Our results therefore showed that biochemical and
morphological markers of PCD varied with intra-erythrocytic parasite development
and that P. falciparum exhibited facets of both apoptosis- and autophagy-like
phenotypes after exposure to febrile temperatures, which may reflect a unique PCD
phenotype.
PMID- 24357803
TI - Identification of the NF-kappaB inhibitor A20 as a key regulator for human
adipogenesis.
AB - The zinc-finger protein A20 is a key player in the negative feedback regulation
of the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-kappaB)
pathway in response to multiple stimuli. Tumor necrosis factor alpha (TNFalpha),
a cytokine with pleiotropic effects on cellular proliferation and
differentiation, dramatically increases A20 expression in all tissues. As
TNFalpha inhibits adipocyte differentiation, we have determined the contribution
of A20 to the adipogenic capacity of human mesenchymal stromal cells (MSCs). Here
we show that A20 is constitutively expressed in MSCs, which previously has been
observed only in cells that are either tumor or immune cells (T/B lymphocytes).
TNFalpha stimulation induced a rapid degradation of A20 protein mediated
exclusively by the proteasome in MSCs and not by caspases. This degradation is
concomitant to the induction of its own mRNA, which suggests that a tight
regulation of NF-kappaB signaling in MSCs is fundamental. On one hand, we
demonstrate that the knockdown of A20-mediated transcript dramatically decreases
the adipogenic capacity of MSCs, which correlates with the phenotype observed in
the presence of TNFalpha. On the other hand, A20 overexpression blocks NF-kappaB
activation and drives to increased adipogenesis, even in the presence of TNFalpha
treatment. In conclusion, our data demonstrate that the presence of A20 allows
MSCs to differentiate into adipocytes by maintaining NF-kappaB signaling at a
basal state.
PMID- 24357804
TI - The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest
and apoptosis in vitro and in vivo.
AB - It has previously been shown that selenite can act as an antitumor agent and
inhibit cancer cell growth, although the mechanism responsible for this effect is
not well understood. In this study, we have shown that selenite can induce cell
cycle arrest and apoptosis in NB4 cells. Selenite treatment of these cells also
inhibited the JNK/ATF2 axis. Further experiments demonstrated that selenite
induced production of reactive oxygen species (ROS) worked as an upstream of the
JNK/ATF2 axis, cell cycle arrest and apoptosis. Inactivation of ATF2 resulted in
decreased affinity of this transcription factor for the promoters of cyclin A,
cyclin D3 and CDK4, which led to the arrest of the NB4 cells in the G0/G1 phase.
Finally, in vivo experiments confirmed the antitumor activity of selenite and the
mechanisms that were described in vitro. Taken together, our results indicate
that selenite-induced ROS arrest NB4 cells at G0/G1 phase through inhibiting the
JNK/ATF2 axis in vitro and in vivo.
PMID- 24357805
TI - Cystatin SN neutralizes the inhibitory effect of cystatin C on cathepsin B
activity.
AB - Cystatin SN (CST1) is one of the several salivary cystatins that form tight
equimolar complexes with cysteine proteases, such as the cathepsins. High
expression of CST1 is correlated with advanced pTNM stage in gastric cancer.
However, the functional role of CST1 in tumorigenesis has not been elucidated. In
this study, we showed that CST1 was highly expressed in colon tumor tissues,
compared with nontumor regions. Increased cell proliferation and invasiveness
were observed in HCT116 cell lines stably transfected with CST1 cDNA (HCT116
CST1) but not in CST3-transfected cells. We also demonstrated that CST1
overexpressing cell lines exhibited increased tumor growth as well as metastasis
in a xenograft nude mouse model. Interestingly, CST1 interacted with cystatin C
(CST3), a potent cathepsin B (CTSB) inhibitor, with a higher affinity than the
interaction between CST3 and CTSB in the extracellular space of HCT116 cells.
CTSB-mediated cellular invasiveness and proteolytic activities were strongly
inhibited by CST3, but in the presence of CST1 CTSB activities recovered
significantly. Furthermore, domain mapping of CST1 showed that the disulfide
bonded conformation, or conserved folding, of CST1 is important for its secretion
and for the neutralization of CST3 activity. These results suggest that CST1
upregulation might be involved in colorectal tumorigenesis and acts by
neutralizing the inhibition of CTSB proteolytic activity by CST3.
PMID- 24357806
TI - Oligomeric amyloid beta induces IL-1beta processing via production of ROS:
implication in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by
progressive neuronal loss and cognitive decline. Oligomeric amyloid beta (oAbeta)
is involved in the pathogenesis of AD by affecting synaptic plasticity and
inhibiting long-term potentiation. Although several lines of evidence suggests
that microglia, the resident immune cells in the central nervous system (CNS),
are neurotoxic in the development of AD, the mechanism whether or how oAbeta
induces microglial neurotoxicity remains unknown. Here, we show that oAbeta
promotes the processing of pro-interleukin (IL)-1beta into mature IL-1beta in
microglia, which then enhances microglial neurotoxicity. The processing is
induced by an increase in activity of caspase-1 and NOD-like receptor family,
pyrin domain containing 3 (NLRP3) via mitochondrial reactive oxygen species (ROS)
and partially via NADPH oxidase-induced ROS. The caspase-1 inhibitor Z-YVAD-FMK
inhibits the processing of IL-1beta, and attenuates microglial neurotoxicity. Our
results indicate that microglia can be activated by oAbeta to induce
neuroinflammation through processing of IL-1beta, a pro-inflammatory cytokine, in
AD.
PMID- 24357807
TI - TRIM32-dependent transcription in adult neural progenitor cells regulates
neuronal differentiation.
AB - In the adult mammalian brain, neural stem cells in the subventricular zone
continuously generate new neurons for the olfactory bulb. Cell fate commitment in
these adult neural stem cells is regulated by cell fate-determining proteins.
Here, we show that the cell fate-determinant TRIM32 is upregulated during
differentiation of adult neural stem cells into olfactory bulb neurons. We
further demonstrate that TRIM32 is necessary for the correct induction of
neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts
differentiate slower and show gene expression profiles that are characteristic of
immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor
cell proliferation and less cell death. Both effects accumulate in an
overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice.
These results highlight the function of the cell fate-determinant TRIM32 for a
balanced activity of the adult neurogenesis process.
PMID- 24357808
TI - The Gout Assessment Questionnaire 2.0: cross-cultural translation into Dutch,
aspects of validity and linking to the International Classification of
Functioning, Disability and Health.
AB - OBJECTIVES: The Gout Assessment Questionnaire 2.0 (GAQ2.0) is a disease-specific
patient-reported outcome measure for gout that distinguishes five different
subscales and comprises overall 31 questions. The aims of this study were to
translate the GAQ2.0 into Dutch and to test clinimetric properties. METHODS:
Recommendations for translation and cross-cultural adaptation were followed and
no cultural adaptations were needed. The resulting Dutch GAQ2.0 was administered
to patients registered at the rheumatology outpatient clinic diagnosed with gout.
Internal consistency was tested using Cronbach's alpha, reliability using
intraclass correlation coefficient (ICC), content validity by linkage to the
International Classification of Functioning, Disability and Health (ICF) and
construct validity by correlating the subscales of the GAQ2.0 with the HAQ
disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36). RESULTS:
A total of 126 patients [106 (84%) male, mean age 66.6 years (s.d. 10.4), mean
disease duration 11.2 years (s.d. 10.6)] completed a number of questionnaires,
including the GAQ2.0, HAQ-DI and SF-36, and underwent a clinical examination.
Internal consistency was sufficient (Cronbach's alpha = 0.83-0.94), except for
the subscale gout medication side effects (Cronbach's alpha = 0.51). Test-retest
reliability was good (ICCs 0.73-0.86) for all subscales, but moderate for the
subscale unmet gout treatment need (ICC 0.56). Gout impact (GI) subscale scores
showed only weak to moderate correlations with HAQ-DI and SF-36, but stronger
emphasis on the emotional consequences of gout. Also, it correlated better with
gout-specific outcomes such as the number of gout flares and pain. CONCLUSION:
The Dutch GAQ2.0 shows sufficient evidence of validity to assess disease-specific
functioning and health in patients with gout and seems to capture different
aspects than those represented in the HAQ and SF-36.
PMID- 24357809
TI - In systemic sclerosis patients, bosentan is safe and effective for digital ulcer
prevention and it seems to attenuate the development of pulmonary arterial
hypertension.
PMID- 24357810
TI - Suppression of soluble T cell-associated proteins by an anti-interferon-alpha
monoclonal antibody in adult patients with dermatomyositis or polymyositis.
AB - OBJECTIVE: The aim of this study was to identify serum markers that are modulated
by an investigational anti-IFN-alpha mAb, sifalimumab, in adult DM or PM
patients. METHODS: In a phase 1b clinical trial, sera were collected from a total
of 48 DM or PM adult patients receiving either placebo for 3 months or
sifalimumab for 6 months. Samples were tested for 128 selected proteins using a
multiplex luminex immunoassay. Muscle biopsies from selected patients were
stained for T cell infiltration using an anti-CD3 antibody. RESULTS: A robust
overexpression of multiple serum proteins in DM or PM patients was observed,
particularly in patients with an elevated baseline type I IFN gene signature in
the blood or muscle. Neutralization of the type I IFN gene signature by
sifalimumab resulted in coordinated suppression of T cell-related proteins such
as soluble IL-2RA, TNF receptor 2 (TNFR2) and IL-18. Muscle biopsies from two
patients with the highest serum protein suppression were selected and found to
have a pronounced reduction of muscle T cell infiltration. Down-regulation of IL
2RA correlated with favourable manual muscle test 8 (MMT-8) alterations in
sifalimumab-dosed patients. CONCLUSION: A reduced level of multiple T cell
associated proteins after sifalimumab but not placebo administration suggests a
suppressive effect of blocking type I IFN signalling on T cell activation and
chemoattraction that may lead to a reduction of T cell infiltration in the muscle
of myositis patients. Further, soluble IL-2RA changes from baseline may serve as
a responsive and/or predictive marker for type I IFN-targeted therapy in adult DM
or PM patients.
PMID- 24357812
TI - Circulating T follicular helper cell and regulatory T cell frequencies are
influenced by B cell depletion in patients with granulomatosis with polyangiitis.
AB - OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare and sometimes fatal
systemic autoimmune disease. ANCAs specific for PR3 are associated with GPA.
Remission in GPA can be achieved through B cell depletion (BCD) therapy. Our aim
was to understand whether the frequencies of T cell subsets are influenced by
BCD. METHODS: The frequencies of circulating T follicular helper cells (cTFHs)
and regulatory T cells (Tregs) from 36 GPA patients including 11 rituximab
treated patients and 10 healthy controls were studied by flow cytometry. The
functional capacity of Tregs was assessed by in vitro co-culture assays. RESULTS:
We observed an increased frequency of cTFHs and a reduced frequency of antigen
experienced Tregs in peripheral blood from GPA patients on conventional therapies
but not in those treated with rituximab compared with healthy controls.
Furthermore, the ratio of cTFHs to Tregs was significantly higher in GPA patients
on conventional therapies than in GPA patients treated with rituximab who were
clinically improved or controls. Whereas Tregs were numerically reduced in GPA
patients on conventional therapy, the suppressive capacity of Tregs on a per cell
basis was not significantly altered in these individuals. CONCLUSION: Our study
illustrated increased cTFHs with decreased antigen-experienced Tregs in GPA
patients on conventional therapies, but in B cell-depleted patients the levels of
cTFHs and Tregs were similar to healthy controls. The negative correlation
between cTFHs and Tregs implies the balance between T cell subsets and its B cell
dependence impact on disease activity in GPA.
PMID- 24357811
TI - Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and
is associated with serum proteins: a cross-sectional, controlled study of carotid
ultrasound.
AB - OBJECTIVES: SSc is associated with an increased prevalence of atherosclerosis
(ATS). This study assessed the prevalence of subclinical ATS as measured by
carotid US and explored serum proteins to identify potential biomarkers of SSc
ATS. METHODS: Forty-six SSc female patients and 46 age- and ethnicity-matched
controls underwent carotid US to assess the presence of plaque and carotid intima
media thickness (CIMT). Abstracted data included demographics, ATS risk factors
and serum measurements [cholesterol, proinflammatory high-density lipoprotein
(piHDL), CRP, lipoproteins]. Serum cytokines/proteins analyses included
circulating type I IFN activity by quantifying IFN-inducible genes, soluble
junctional adhesion molecule A (sJAM-A) and 100 serum proteins by using a
microplate-based multiplex platform. Proteins significant at P < 0.05 on
bivariate analyses for the presence of plaque were used to develop a composite
measure. RESULTS: Patients with SSc had more plaque (45.6% vs 19.5%, P = 0.01)
but similar CIMT compared with controls. Multiplex analysis detected significant
associations between serum proteins of inflammation, vasculopathy and fibrosis
with ATS in SSc, including IL-2, IL-6, CRP, keratinocyte growth factor,
intercellular adhesion molecule 1, endoglin, plasminogen activator inhibitor 1
and insulin-like growth factor binding protein 3 associated with carotid plaque.
Myeloid progenitor inhibitory factor 1, serum amyloid A, thrombomodulin, N
terminal pro-brain natriuretic peptide (BNP), and Clara cell secretory protein 16
kD correlated with CIMT. The median composite score for the plaque group was 6
and for the no plaque group it was 2 (P < 0.0001). CONCLUSION: Patients with SSc
have a higher prevalence of carotid plaque than matched controls, and patients
with SSc-plaque vs patients without plaque have elevated serum proteins
implicated in both vasculopathy and fibrosis. Further studies are needed to
evaluate the role of these proteins in SSc compared with healthy controls.
PMID- 24357813
TI - It's like a juggling act: rheumatoid arthritis patient perspectives on daily life
and flare while on current treatment regimes.
AB - OBJECTIVE: The objective of this study was to explore patients' experiences of RA
daily life while on modern treatments. METHODS: The methods of this study
comprised semi-structured interviews with 15 RA patients, analysed using
inductive thematic analysis. RESULTS: Four themes suggest patients experience
life with RA along a continuum from RA in the background to the foreground of
their lives, underpinned by constant actions to maintain balance. Living with RA
in the background shows patients experience continuous, daily symptoms, which
they mediate through micromanagement (mediating the impact of RA on daily life),
while learning to incorporate RA into their identity (redefining me). RA moving
into the foreground shows patients experience fluctuating symptoms (unwelcome
reminders) that may or may not lead to a flare (trying to make sense of
fluctuation). Dealing with RA in the foreground shows how patients attempt to
manage RA flares (trying to regain control) and decide to seek medical help only
after feeling they are losing control. Patients employ a stepped approach to self
management (mediation ladder) as symptoms increase, with seeking medical help
often seen as the last resort. Patients seek to find a balance between managing
their fluctuating RA and living their daily lives. CONCLUSION: Patients move back
and forth along a continuum of RA in the background vs the foreground by
balancing self-management of symptoms and everyday life. Clinicians need to
appreciate that daily micromanagement is needed, even on current treatment
regimes. Further research is needed to quantify the level and impact of daily
symptoms and identify barriers and facilitators to seeking help.
PMID- 24357815
TI - Improving outcomes - changing behaviours.
PMID- 24357814
TI - Abscopal effect of low-LET gamma-radiation mediated through Rel protein signal
transduction in a mouse model of nontargeted radiation response.
AB - Ascertaining the ionizing radiation (IR)-induced bystander response and its
preceding molecular regulation would increase our understanding of the mechanism
of acute and delayed radiobiological effects. Recent evidence clearly prompted
that radiation-induced nuclear factor kappa B (NF-kappaB) would play a key role
in bystander responses in nontargeted cells. Accordingly, we investigated the
orchestration of NF-kappaB signaling after IR in a nontargeted distant organ.
Heart tissues from C57/BL6 mice either mock irradiated or exposed (limited to
lower abdomen 1 cm diameter) to single-dose IR (SDR: 2 or 10 Gy) or fractionated
IR (FIR, 2 Gy per day for 5 days) were examined for onset of abscopal NF-kappaB
signal transduction, translated activity, downstream functional signaling and
associated DNA damage. Radiation significantly induced NF-kappaB DNA binding
activity in nontargeted heart. Transcriptional profiling showed that 51, 46 and
26 of 88 genes were significantly upregulated after 2 Gy, 10 Gy and FIR. Of these
genes, 22 showed dose- and fractionation-independent upregulation.
Immunohistochemistry revealed a robust increase in p65 and cMyc expression in
distant heart after SDR and FIR. Immunoblotting revealed increased
phosphorylation of p38 after 2 Gy and extracellular signal-regulated kinases 1/2
after 10 Gy in nontargeted heart. In addition, IR exposure significantly enhanced
DNA fragmentation in nontargeted heart. Together, these data clearly indicated an
induced abscopal response in distant organ after clinically relevant IR doses.
More importantly, the results imply that orchestration of NF-kappaB signal
transduction in nontargeted tissues may serve as an effector and could play a key
role in induced abscopal responses.
PMID- 24357816
TI - An interview with the editor. Interview by Nicola Innes.
PMID- 24357817
TI - Baseline caries prevalence was the most accurate single predictor of caries risk
in all age groups.
AB - DATA SOURCES: The Cochrane CENTRAL and Medline databases and reference lists of
identified were searched. STUDY SELECTION: Prospective longitudinal cohorts or
randomised controlled trials were included. DATA EXTRACTION AND SYNTHESIS: Study
assessment and data extraction were carried out independently by at least two
reviewers. The quality of studies was assessed using the QUADAS and AMSTAR tools.
The overall quality of evidence was assessed using the GRADE approach. RESULTS:
90 studies were included, seven were of high quality, 35 of moderate quality and
the rest poor. The accuracy of multivariate models was higher for pre-school
children than for schoolchildren/adolescents. As the models had rarely been
tested in independent populations their accuracy is uncertain. The single
predictor baseline caries experience had moderate/good accuracy in pre-school
children and limited accuracy in schoolchildren/adolescents. In general, the
quality of evidence was limited. CONCLUSIONS: Multivariate models and baseline
caries prevalence performed better in pre-school children than in school
children/adolescents. Baseline caries prevalence was the most accurate single
predictor in all age groups. The heterogeneity of populations, models, outcome
criteria, measures and reporting hampered the synthesis of results. There is a
great need to standardise study design, outcome measures and reporting of data in
studies on caries risk assessment. The accuracy of prediction models should be
validated in at least one independent population.
PMID- 24357818
TI - Limited evidence on the best position for prosthetic margins.
AB - DATA SOURCES: The Cochrane Central Register of Controlled Trials (CENTRAL),
Cochrane Database of Systematic reviews, Medline, Google Scholar and Scopus
databases were searched along with handsearching of the Journal of Prosthetic
Dentistry, International Journal of Prosthodontics, Journal of Dentistry and
Caries Research. STUDY SELECTION: Randomised controlled clinical trials,
prospective or retrospective studies or case-control observational studies
reporting on caries susceptibility of teeth serving as abutments for prosthetic
restorations were included. Only English language studies were included. DATA
EXTRACTION AND SYNTHESIS: Study selection and quality assessment was carried out
by two reviewers. Trials were compared by grouping abutments teeth/abutment
surfaces with subgingival margins. Caries incidence was evaluated as a
dichotomous variable. The risk ratio (RR) for caries incidence of prosthetic
margins was calculated for the direct comparisons and pooled using a random
effects model. The overall quality of evidence supporting the association between
secondary caries and margin placement was assessed using the GRADE system.
RESULTS: Twenty-two studies were included, representing 2,648 prosthetic
restorations placed in 1,242 patients with mean follow-up time ranging from two
to 11.4 years. A random effects meta-analysis was performed on two studies. This
found a pooled risk ratio (RR) for secondary caries of sub-gingival margins at up
to five years of 1.25 (95% CI: 0.70 to 2.22). At ten years of follow-up, the RR
was1.22 (95% CI: 0.81 to 1.83) and at 15 years 0.67 (95% CI: 0.45 to 1.00).
CONCLUSIONS: This systematic review and meta-analysis failed to detect a
significantly different secondary caries rate of subgingivally located prosthetic
margins in the short to mid-term (10 years). Due to the small number and the
limitations of the included studies the results do not provide conclusive
evidence as to the effect of prosthetic margin placement on the incidence of
secondary caries.
PMID- 24357819
TI - Study suggests dentine bonding agents provided better relief from dentine
hypersensitivity than a desensitising toothpaste.
AB - STUDY DESIGN: Randomised, controlled, single-blind, three-arm parallel-group
trial set in general dental practice with a single general dental practitioner
operator/assessor. INTERVENTION: Seventy-five adult patients, with basic
periodontal examination scores of 0 in all sextants, good oral hygiene, at least
one sensitive tooth (not diagnosed as pulpitis) and willing to comply with the
trial regime were entered into the trial and randomised. Seventy-two participants
completed the study. The three interventions were; non-desensitising toothpaste
(Colgate Cavity Protection Regular, Colgate-Palmolive, USA), desensitising
toothpaste (Colgate Sensitive Fresh Stripe, Colgate-Palmolive, USA) and dentine
bonding agent (Seal and Protect, Denpsly, USA). The non-desensitising toothpaste
and desensitising toothpastes were provided to the subjects for use at home but
dentine bonding agent was applied in the surgery. OUTCOME MEASURE: Dentinal
hypersensitivity was measured using a participant completed Visual Analogue Scale
(VAS) at baseline, two weeks, three months and six months. At baseline and six
months a standardised air blast to the buccal cervical root stimulus was used
with the VAS. At two weeks and at three months participants self-completed the
VAS at home with no stimulus. RESULTS: Although there was a reduction in dentinal
hypersensitivity over time for all three groups, dentinal hypersensitivity
reduced significantly (p<0.0001) in both desensitising toothpaste and dentine
bonding agent groups. The mean VAS scores in the dentine bonding agent group were
statistically significantly lower when compared to both non-desensitising
toothpaste (p<0.001) and desensitising toothpaste (p<0.001). In addition, mean
scores for non-desensitising toothpaste were higher than desensitising toothpaste
(p<0.05). CONCLUSIONS: Dentine bonding agents provided the greatest improvement
in dentinal hypersensitivity at two weeks and six months. This reduction was
greater than that achieved with the desensitising and non-desensitising
toothpastes tested.
PMID- 24357820
TI - Pregnancy gingivitis and causal inference.
AB - DATA SOURCES: The PubMed and Embase databases were searched together with hand
searching of the Journal of Periodontology, Journal of Periodontal Research and
Journal of Clinical Periodontology. The reference lists of identified articles
were also searched. STUDY SELECTION: Prospective cohort or cross-sectional
studies assessing the effect of pregnancy on gingival inflammation evaluated by
the gingival index and/or bleeding on probing were included. Study quality was
assessed using the Newcastle-Ottawa scale (NOS). DATA EXTRACTION AND SYNTHESIS:
Study assessment and data extraction were carried out independently by two
reviewers, with disputes resolved by a third reviewer. Mean values of primary and
secondary outcomes were directly pooled and analysed with weighted mean
differences (WMDs) and 95% confidence intervals (CIs), considering independently
each study design (cohort and cross-sectional). Study specific estimates were
pooled with both the fixed- and random-effect models. RESULTS: Forty-four
articles representing 33 studies (14 cohort and 19 cross-sectional) were
included. Meta-analyses revealed a significantly lower GI in pregnant women in
the first term compared with those in their second or third term of pregnancy; a
lower mean GI score in post-partum women compared with women in their second [WMD
= 0.143; 95% CI (0.031; 0.255); p = 0.012] or third term [WMD = 0.256; 95% CI
(0.151; 0.360); p < 0.001] of pregnancy, when considering cohort studies; non
pregnant women had lower mean GI values than women in their second or third term
of pregnancy. Small changes in plaque levels were reported. CONCLUSIONS: The
results of this systematic review confirm that gingival inflammation is
significantly increased throughout pregnancy and when comparing pregnant versus
post-partum or non-pregnant women, without a concomitant increase in plaque
levels. However, this information should be considered with caution, due to the
small number of studies included in the meta-analyses, the low quality of the
included studies, differences in study design, absence of a periodontal diagnosis
at baseline and performance of periodontal treatment in some cases. No
conclusions could be drawn regarding secondary outcomes such as microbiological,
immunological and patient-centred data, because no meta-analyses were possible
for these factors. Future studies with higher quality should be designed to
answer these questions.
PMID- 24357821
TI - Different loading times for dental implants - no clinically important
differences?
AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane
Central Register of Controlled Trials (CENTRAL), Medline, and Embase databases
were searched. Reference lists of identified articles were also scanned for
relevant papers. There were no restrictions on language or date of publication.
STUDY SELECTION: Randomised controlled trials (RCTs) of parallel group design and
of split-mouth design including root-form osseointegrated dental implants having
a follow-up of four months to one year after loading were included. DATA
EXTRACTION AND SYNTHESIS: Data were independently extracted, in duplicate, by at
least two review authors. The outcome measures were prosthesis and implant
failures and radiographic marginal bone level changes. Risk of bias was assessed
for each trial by at least two review authors. Results were combined using fixed
effect models with mean differences (MD) for continuous outcomes and risk ratios
(RR) for dichotomous outcomes with 95% confidence intervals (CI). RESULTS: Twenty
six trials involving a total of 1217 participants and 2120 implants were
included. The risk of bias was low in three trials, high in 12 and unclear for
the remaining eleven. In nine studies there were no prosthetic failures within
the first year, with no implant failures in seven studies and the mean rate of
implant failure in all 26 trials was a low 2.5%. From 15 RCTs comparing immediate
with conventional loading there was no evidence of a difference in either
prosthesis failure (RR 1.87; 95% CI 0.70 to 5.01; 8 trials) or implant failure
(RR 1.65; 95% CI 0.68 to 3.98; 10 trials) in the first year. However, there is
some evidence of a small reduction in bone loss favouring immediate loading (MD
0.10 mm; 95% CI -0.20 to -0.01; P = 0.03; 9 trials), but this very small
difference may not be clinically important. From three RCTs which compared early
loading with conventional loading, there is insufficient evidence to determine
whether or not there is a clinically important difference in prosthesis failure,
implant failure or bone loss. Six RCTs compared immediate and early loading and
found insufficient evidence to determine whether or not there is a clinically
important difference in prosthesis failure, implant failure or bone loss. From
the two trials that compared occlusal loading with non-occlusal loading there is
insufficient evidence to determine whether there is a clinically important
difference in the outcomes of prosthesis failure, implant failure or bone loss.
No trials were identified which evaluated progressive loading of implants.
CONCLUSIONS: Overall there was no convincing evidence of a clinically important
difference in prosthesis failure, implant failure or bone loss associated with
different loading times of implants. More well-designed RCTs are needed and
should be reported according to the CONSORT guidelines.
PMID- 24357822
TI - Corticosteroids decrease pain, swelling and trismus.
AB - DATA SOURCES: PubMed, Scopus, Medline and Cochrane Oral Health Group's Trials
Register, CENTRAL. Limited to English language. STUDY SELECTION: Randomised
control trials comparing preoperative steroids (in any formulation, dose or
route) with placebo or no treatment in patients of any age, having extraction of
one or more impacted third molars (under local or general anaesthesia or with
intravenous sedation). DATA EXTRACTION AND SYNTHESIS: Two authors reviewed titles
and abstracts of all articles to select those that met the inclusion criteria.
The studies were classified by active principles, doses and treatment
administration route. No meta-analysis was conducted and a tabular descriptive
summary was presented. RESULTS: There were 28 studies (one meta-analysis and 27
randomised control trials) included in the descriptive account and from which
conclusions were drawn. CONCLUSIONS: The use of corticosteroids in third molar
extractions reduces the degree of trismus and inflammation. Parenteral
administration seems to be more effective than oral administration as does taking
the corticosteroids before rather than after surgery. Further comparative studies
using different corticosteroids, doses and administration routes are needed to
establish the most effective regime for reducing pain, trismus and inflammation
after extraction of third molars.
PMID- 24357823
TI - Facemask therapy between ages six to ten years may lead to short term
improvements for Class III malocclusions.
AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane
Central Register of Controlled Trials (CENTRAL), Medline and Embase databases
were searched. STUDY SELECTION: Randomised controlled trials of orthodontic
treatments to correct prominent lower front teeth. DATA EXTRACTION AND SYNTHESIS:
Study screening and data extraction and risk of bias assessment were carried out
independently by two reviewers. Meta-analysis was only undertaken when studies of
similar comparisons reported comparable outcome measures. RESULTS: Seven RCTs
with a total of 339 participants were included in this review. Three studies were
at high risk of bias, three unclear and one at low risk. Four studies reported on
the use of a facemask, two on the chin cup, one on the tandem traction bow
appliance, and one on mandibular headgear. One study reported on both the chin
cup and mandibular headgear appliances.One study (n = 73, low quality evidence),
comparing a facemask to no treatment, reported a mean difference (MD) in overjet
of 4.10 mm (95% confidence interval (CI) 3.04 to 5.16; P value < 0.0001)
favouring the facemask treatment. Two studies comparing facemasks to untreated
control did not report the outcome of overjet. Three studies (n = 155, low
quality evidence) reported ANB (an angular measurement relating the positions of
the top and bottom jaws) differences immediately after treatment with a facemask
when compared to an untreated control. The pooled data showed a statistically
significant MD in ANB in favour of the facemask of 3.93 degrees (95% CI 3.46 to
4.39; P value < 0.0001). There was significant heterogeneity between these
studies (I(2) = 82%). This is likely to have been caused by the different
populations studied and the different ages at the time of treatment.One study (n
= 73, low quality evidence) reported outcomes of the use of the facemask compared
to an untreated control at three years follow-up. This study showed that
improvements in overjet and ANB were still present three years post-treatment. In
this study, adverse effects were reported, but due to the low prevalence of
temporomandibular (TMJ) signs and symptoms no analysis was undertaken.Two studies
(n = 90, low quality evidence) compared the chin cup with an untreated control.
Both studies found a statistically significant improvement in ANB, and one study
also found an improvement in the Wits appraisal. Data from these two studies were
not suitable for pooling.A single study of the tandem traction bow appliance
compared to untreated control (n = 30, very low quality evidence) showed a
statistically significant difference in both overjet and ANB favouring the
intervention group. CONCLUSIONS: There is some evidence that the use of a
facemask to correct prominent lower front teeth in children is effective when
compared to no treatment on a short-term basis. However, in view of the general
poor quality of the included studies, these results should be viewed with
caution. Further randomised controlled trials with long follow-up are required.
PMID- 24357824
TI - No reliable evidence to guide initial arch wire choice for fixed appliance
therapy.
AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane
Central Register of Controlled Trials (CENTRAL), Medline and Embase databases
were searched. Conference proceedings and abstracts from the British Orthodontic
Conference European Orthodontic Conference and the International Association for
Dental Research were also searched together with the reference lists of
identified studies. Study authors were contacted for additional information.
STUDY SELECTION: Randomised controlled trials of initial arch wire involving
participants with upper and/or lower full arch fixed orthodontic appliances were
included. DATA EXTRACTION AND SYNTHESIS: Study selection, data extraction and
risk of bias assessment were carried out independently by at least two reviewers.
RESULTS: Nine RCTs with 571 participants were included in this review. All trials
were at high risk of bias. All trials had at least one potentially confounding
factor (such as bracket type, slot size, ligation method, extraction of teeth)
which is likely to have influenced the outcome and was not controlled in the
trial. None of the trials reported the important adverse outcome of root
resorption. The comparisons were made between:Multistrand stainless steel initial
arch wires compared to superelastic nickel titanium (NiTi) initial arch wires.
There were four trials in this group, with different comparisons and outcomes
reported at different times. No meta-analysis was possible. There is insufficient
evidence from these trials to determine whether or not there is a difference in
either rate of alignment or pain between stainless steel and NiTi initial arch
wires.Conventional (stabilised) NiTi initial arch wires compared to superelastic
NiTi initial arch wires. There were two trials in this group, one reporting the
outcome of alignment over six months and the other reporting pain over one week.
There is insufficient evidence from these trials to determine whether or not
there is any difference between conventional (stabilised) and superelastic NiTi
initial arch wires with regard to either alignment or pain.Single-strand
superelastic NiTi initial arch wires compared to other NiTi (coaxial, copper NiTi
(CuNiTi) or thermoelastic) initial arch wires. The three trials in this
comparison each compared a different product against single-strand superelastic
NiTi. There is very weak unreliable evidence, based on one very small study (n =
24) at high risk of bias, that coaxial superelastic NiTi may produce greater
tooth movement over 12 weeks, but no information on associated pain or root
resorption. This result should be interpreted with caution until further research
evidence is available. There is insufficient evidence to determine whether or not
there is a difference between either thermoelastic or CuNiTi and superelastic
NiTi initial arch wires. CONCLUSIONS: There is no reliable evidence from the
trials included in this review that any specific initial arch wire material is
better or worse than another with regard to speed of alignment or pain. There is
no evidence at all about the effect of initial arch wire materials on the
important adverse effect of root resorption. Further well-designed and conducted,
adequately-powered RCTs are required to determine whether the performance of
initial arch wire materials as demonstrated in the laboratory, makes a clinically
important difference to the alignment of teeth in the initial stage of
orthodontic treatment in patients.
PMID- 24357825
TI - No randomised trials of interventions to manage relapse of lower incisors after
orthodontic treatment.
AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane
Central Register of Controlled Trials (CENTRAL), Medline and Embase databases
were searched with no language or date restrictions. Handsearching of a number of
orthodontic journals was undertaken. STUDY SELECTION: Randomised controlled
trials (RCTs) comparing fixed and removable treatment options for the management
of relapsed lower front teeth after orthodontic treatment were to be considered.
RCTs involving patients with craniofacial deformities/syndromes or serious
skeletal deformities were excluded. DATA EXTRACTION AND SYNTHESIS: Two review
authors, independently and in duplicate, assessed the results of the searches to
identify studies for inclusion. The Cochrane Collaboration statistical guidelines
were to be followed for data synthesis. RESULTS: No trials were identified.
CONCLUSIONS: This review has revealed that there was no evidence from RCTs to
show that one intervention was superior to another to manage the relapse of the
alignment of lower front teeth using any method or index, aesthetic assessment by
participants and practitioners, treatment time, patient discomfort, quality of
life, cost-benefit considerations, stability of the correction, and side effects
including pain, gingivitis, enamel decalcification and root resorption. There is
an urgent need for RCTs in this area to identify the most effective and safe
method for managing the relapse of alignment of the lower front teeth.
PMID- 24357826
TI - A better definition of counselling strategies is needed to define effectiveness
in temporomandibular disorders management.
AB - DATA SOURCES: The Cochrane Library databases and Medline were searched along with
the reference lists of identified articles and The Journal of the American Dental
Association, Journal of Orofacial Pain and Journal of Oral Rehabilitation. STUDY
SELECTION: Controlled clinical trials in which the intervention included the
treatment in at least one group with counselling techniques were included.
Studies in English, Portuguese or Spanish were considered. DATA EXTRACTION AND
SYNTHESIS: A standard data set was retrieved from the articles and a qualitative
synthesis was undertaken. RESULTS: Seven randomised controlled trials involving a
total of 489 patients were included. Follow-up periods ranged from four weeks to
12 months. The studies suggested that counselling was able to improve tenderness
upon masticatory muscle palpation and maximum mouth opening with and without pain
in patients with TMD, with similar results to those of interocclusal appliances
approaches. CONCLUSIONS: Although counselling- and self-management-based
therapies could be a conservative low-cost and beneficial treatment alternative
for treating TMD, with good results for the relief and control of TMD signs and
symptoms by improving psychological domains and potentially reducing harmful
behaviours, the evidence remains unclear due to the small number of controlled
and randomised well-designed clinical trials. Thus, further studies with higher
level of evidence and more representative samples should be conducted to validate
the performance of this treatment modality.
PMID- 24357827
TI - SPIRIT 2013.
PMID- 24357828
TI - Case Reports - the CARE statement.
PMID- 24357832
TI - The application of an in situ karyotyping technique for mesenchymal stromal
cells: a validation and comparison study with classical G-banding.
AB - The cytogenetic analysis of mesenchymal stromal cells (MSCs) is essential for
verifying the safety and stability of MSCs. An in situ technique, which uses
cells grown on coverslips for karyotyping and minimizes cell manipulation, is the
standard protocol for the chromosome analysis of amniotic fluids. Therefore, we
applied the in situ karyotyping technique in MSCs and compared the quality of
metaphases and karyotyping results with classical G-banding and chromosomal
abnormalities with fluorescence in situ hybridization (FISH). Human adipose- and
umbilical cord-derived MSC cell lines (American Type Culture Collection PCS-500
011, PCS-500-010) were used for evaluation. The quality of metaphases was
assessed by analyzing the chromosome numbers in each metaphase, the overlaps of
chromosomes and the mean length of chromosome 1. FISH was performed in the
interphase nuclei of MSCs for 6q, 7q and 17q abnormalities and for the
enumeration of chromosomes via oligo-FISH in adipose-derived MSCs. The number of
chromosomes in each metaphase was more variable in classical G-banding. The
overlap of chromosomes and the mean length of chromosome 1 as observed via in
situ karyotyping were comparable to those of classical G-banding (P=0.218 and
0.674, respectively). Classical G-banding and in situ karyotyping by two
personnel showed normal karyotypes for both cell lines in five passages. No
numerical or structural chromosomal abnormalities were found by the interphase
FISH. In situ karyotyping showed equivalent karyotype results, and the quality of
the metaphases was not inferior to classical G-banding. Thus, in situ karyotyping
with minimized cell manipulation and the use of less cells would be useful for
karyotyping MSCs.
PMID- 24357833
TI - Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell
differentiation after ischemic brain injury.
AB - Neural stem cells (NSCs) have been suggested as a groundbreaking solution for
stroke patients because they have the potential for self-renewal and
differentiation into neurons. The differentiation of NSCs into neurons is
integral for increasing the therapeutic efficiency of NSCs during inflammation.
Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by
oxidative stress and inflammation, which is the fundamental pathology of brain
damage in stroke. ASK1 may be involved in the early inflammation response after
stroke and may be related to the differentiation of NSCs because of the
relationship between ASK1 and the p38 mitogen-activated protein kinase pathway.
Therefore, we investigated whether ASK1 is linked to the differentiation of NSCs
under the context of inflammation. On the basis of the results of a microarray
analysis, we performed the following experiments: western blot analysis to
confirm ASK1, DCX, MAP2, phospho-p38 expression; fluorescence-activated cell
sorting assay to estimate cell death; and immunocytochemistry to visualize and
confirm the differentiation of cells in brain tissue. Neurosphere size and cell
survival were highly maintained in ASK1-suppressed, lipopolysaccharide (LPS)
treated brains compared with only LPS-treated brains. The number of positive
cells for MAP2, a neuronal marker, was lower in the ASK1-suppressed group than in
the control group. According to our microarray data, phospho-p38 expression was
inversely linked to ASK1 suppression, and our immunohistochemistry data showed
that slight upregulation of ASK1 by LPS promoted the differentiation of
endogenous, neuronal stem cells into neurons, but highly increased ASK1 levels
after cerebral ischemic damage led to high levels of cell death. We conclude that
ASK1 is regulated in response to the early inflammation phase and regulates the
differentiation of NSCs after inflammatory-inducing events, such as ischemic
stroke.
PMID- 24357834
TI - A co-occurrence of familial isolated cherry red spot and multiple lens opacities.
AB - PURPOSE: To present a co-occurrence of familial isolated cherry red spot (CRS)
and multiple lens opacities in all siblings from the same family without any
other systemic or ocular diseases. METHODS: Four siblings from the same family
had bilateral punctate lens opacities and bilateral CRS at the macula. RESULTS:
The oldest one had left eye exotropia and amblyopia, otherwise the other siblings
had no additional ocular findings. Systemic investigation, physical examination,
and laboratory tests were within normal limits. CONCLUSION: Bilateral isolated
CRS along with punctate lens opacities were seen in all siblings from the same
family without any systemic and ocular diseases.
PMID- 24357835
TI - The pathogenesis of keratoconus.
AB - Keratoconus (KC) is a common degenerative condition that frequently results in
visual loss with an onset typically in early adulthood. It is the single most
common reason for keratoplasty in the developed world. The cause and underlying
pathological mechanism are unknown, but both environmental and genetic factors
are thought to contribute to the development of the disease. Various strategies
have been employed to address the gap in our understanding of this complex
disease, with the expectation that over time more sophisticated therapies will be
developed. In this review we summarise our current knowledge of the aetiology and
risk factors associated with KC.
PMID- 24357836
TI - Myopia, an underrated global challenge to vision: where the current data takes us
on myopia control.
AB - Myopia is the most frequent cause of distance impairment in the world and is
creating an alarming global epidemic with deleterious ramifications for the
quality of life and economic health of individuals and nations as a whole. In
addition to being immediately disadvantageous, myopia increases the risk of
serious disorders such as myopic macular degeneration, retinal detachment,
glaucoma, and cataract and is a leading cause of visual impairment and blindness
across many countries. The reduction in age of onset of myopia is of great
concern since the earlier the onset, the more myopic the individual will become,
with all the attendant increased risks of accompanying debilitating eye
conditions. The economic burden is great; both in consequences of uncorrected
refractive error and also in the provision of devices for correcting visual
acuity. Earlier onset of myopia increases the lifetime economic burden related to
loss of productivity and independence, leading to a reduced quality of life.
Recent data suggest addressing accommodation per se has little direct
amelioration of myopia progression. Pharmacological interventions that effect
changes in the sclera show promising efficacy, whereas optical interventions
based on a myopic shift in the retinal image are proving to effect up to 55%
reduction in the rate of progression of myopia. Early contact lens and spectacle
interventions that reduce the rate of progression of myopia are able to
significantly reduce the burden of myopia. These non-pharmacological
interventions show profound promise in reducing the overall associated morbidity
of myopia.
PMID- 24357837
TI - Genetic and environmental effects on myopia development and progression.
AB - This review aims at elucidating the interaction between genetic and environmental
factors in the aetiology of primarily low myopia. Genetics greatly influence the
growth of the eye, but the fine correlation between the components of refraction
for the eye to become emmetrope is affected by environmental factors such as
education, metabolism, physical activity, and outdoor activity.
PMID- 24357838
TI - Spontaneous superior ophthalmic vein thrombosis: a rare entity with potentially
devastating consequences.
AB - PURPOSE: Spontaneous superior ophthalmic vein thrombosis (SOVT) is a rare entity.
We describe three patients with spontaneous ophthalmic vein thrombosis, each with
various risk factors. PATIENTS AND METHODS: A retrospective review of three
patients with a diagnosis of superior ophthalmic vein thrombosis. Clinical
characteristics, radiographic features, management techniques and outcomes are
described. RESULTS: All patients presented with unilateral painful proptosis. Two
patients had intact light perception, whereas one patient presented with absent
light perception. All patients had identifiable risk factors for thrombosis,
which included sickle cell trait, hereditary hemorrhagic telangectasia and colon
cancer with recurrent deep vein thrombosis. Anticoagulation was initiated in two
patients. Resolution of proptosis was seen in all patients, with no recovery of
vision in one patient. CONCLUSIONS: Risk factors for spontaneous superior
ophthalmic vein thrombosis are multifactorial. MRI and MRV confirm the diagnosis
of SOVT. Despite urgent intervention devastating visual loss may occur.
PMID- 24357839
TI - Local safety of repeated intravitreal Ozurdex.
PMID- 24357840
TI - The psychological well-being and appearance concerns of patients presenting with
ptosis.
AB - PURPOSE: Ptosis affects both the function and appearance of the eyes and face,
because of drooping of the eyelids. Previous research has focused on functional
impairment; however, similar appearance altering eye conditions have been
demonstrated to have major impacts on psychosocial functioning. METHODS: This
study examines the psychological well-being and appearance concerns of patients
presenting with ptosis recruited from Bristol Eye Hospital using validated
questionnaires focusing on demographics and psychosocial factors before surgery.
RESULTS: Patients reported higher levels of anxiety, depression, and appearance
concern than population norms, with scores comparable to previous research
examining the impact of other disfiguring eye conditions. Gender differences were
observed, with almost half of females experiencing significant psychosocial
issues related to appearance concern about their ptosis compared with 20% of
males. Linear regressions revealed that the main predictor of poor adjustment to
the appearance of ptosis was the level of concern an individual had regarding the
negative perceptions of other people. These results implicate psychosocial
factors and demographics as predictors of the development of appearance-related
distress and compromised psychological well-being for patients with ptosis who
are currently seeking surgery. CONCLUSIONS: This study provides clinicians with a
greater understanding of the concerns of affected patients, and treatment
motivations. The findings may also inform the development of patient reported
outcome measures and support for patients, which targets the psychosocial impact
of the condition.
PMID- 24357842
TI - Intravitreal foreign body following intravitreal anti-VEGF injection: a case
report.
PMID- 24357841
TI - Initial central scotomas vs peripheral scotomas in normal-tension glaucoma:
clinical characteristics and progression rates.
AB - PURPOSE: To investigate clinical characteristics and progression rates of the
initial central scotomas (ICS) compared with the initial peripheral scotomas
(IPS) in normal-tension glaucoma (NTG) patients. METHODS: Among NTG patients
showing a single hemifield defect and who performed more than five reliable
standard visual field (VF) tests, medical records of ICS (involvement of >=3
adjacent points with P<5% within the central 12 degrees of fixation and one
point with a P<0.01 within the central 6 degrees of fixation) (n=32) or IPS (no
VF abnormality within the central 6 degrees of fixation) (n=34) were
retrospectively analyzed. The changes of mean thresholds from 10 zones of the
glaucoma hemifield test, central 6 degrees and 12 degrees zones, peripheral
zones other than central 6 degrees and 12 degrees , and the entire hemifield
were inspected. To calculate the progression rates, linear mixed-effect model was
employed. RESULTS: There were no significant differences between the two groups
in age, gender, ocular factors including baseline/mean treated intraocular
pressure, and systemic factors including systolic or diastolic blood
pressure/perfusion pressure, mean ocular perfusion pressure (all P>0.05). There
were no significant differences in baseline mean deviation and pattern standard
deviation (P>0.05) between the two groups, but VF index was significantly lower
in ICS group than in IPS group (P=0.001). The progression rates between the two
groups were not significantly different in all zones we investigated (all
P>0.05). CONCLUSIONS: Newly diagnosed cases of NTG with ICS may not differ from
those with IPS in clinical characteristics and progression rates under treatment.
PMID- 24357843
TI - Primary B-cell lymphoma of the ciliary body with 360 degrees ('ring'-like)
growth pattern.
PMID- 24357844
TI - Clinical management of progressive myopia.
AB - Myopia has been increasing in prevalence throughout the world, reaching over 90%
in some East Asian populations. There is increasing evidence that whereas
genetics clearly have an important role, the type of visual environment to which
one is exposed to likely influences the onset, progression, and cessation of
myopia. Consequently, attempts to either modify the environment or to reduce the
exposure of the eye to various environmental stimuli to eye growth through the
use of various optical devices are well under way at research centers around the
globe. The most promising of current treatments include low-percentage atropine,
bifocal soft contact lenses, orthokeratology, and multifocal spectacles. These
methods are discussed briefly and are then categorized in terms of their expected
degree of myopia progression control. A clinical strategy is presented for
selecting the most effective treatment for the appropriate type of patient at the
optimal stage of refractive development to achieve the maximum control of myopia
progression.
PMID- 24357845
TI - Surgical management of WEBINO syndrome following pineal gland lesion removal.
PMID- 24357846
TI - Response to Hernandez-Martinez et al.
PMID- 24357847
TI - The Angelina effect: immediate reach, grasp, and impact of going public.
AB - BACKGROUND: In May 2013, Angelina Jolie revealed in a New York Times opinion
piece that she had undergone a preventive double mastectomy because she had a
family history of cancer and carried a rare mutation of the BRCA1 gene. Media
coverage has been extensive, but it is not obvious what messages the public took
from this personal health story. METHODS: We conducted a survey with a
representative national online panel of 2,572 adults. Participants described
their awareness and identified information sources for the Angelina Jolie news
story. They also reported their understanding, reactions, perceptions, and
subsequent activities related to the story. We asked questions pertaining to
personal and societal breast cancer risk and hypothetical questions regarding
preventive surgery if the respondent or a family member were in the same position
as Ms Jolie. Demographic information was collected, as was family risk for breast
and ovarian cancer, and a gauge of numeracy. RESULTS: While three of four
Americans were aware of Angelina Jolie's double mastectomy, fewer than 10% of
respondents had the information necessary to accurately interpret Ms Jolie's risk
of developing cancer relative to a woman unaffected by the BRCA gene mutation.
Awareness of the Angelina Jolie story was not associated with improved
understanding. CONCLUSION: While celebrities can bring heightened awareness to
health issues, there is a need for these messages to be accompanied by more
purposeful communication efforts to assist the public in understanding and using
the complex diagnostic and treatment information that these stories convey.
PMID- 24357848
TI - Cystic fibrosis carrier screening in a North American population.
AB - PURPOSE: The aim of this study was to compare the mutation frequency distribution
for a 32-mutation panel and a 69-mutation panel used for cystic fibrosis carrier
screening. Further aims of the study were to examine the race-specific detection
rates provided by both panels and to assess the performance of extended panels in
large-scale, population-based cystic fibrosis carrier screening. Although genetic
screening for the most common CFTR mutations allows detection of nearly 90% of
cystic fibrosis carriers, the large number of other mutations, and their
distribution within different ethnic groups, limits the utility of general
population screening. METHODS: Patients referred for cystic fibrosis screening
from January 2005 through December 2010 were tested using either a 32-mutation
panel (n = 1,601,308 individuals) or a 69-mutation panel (n = 109,830). RESULTS:
The carrier frequencies observed for the 69-mutation panel study population
(1/36) and Caucasian (1/27) and African-American individuals (1/79) agree well
with published cystic fibrosis carrier frequencies; however, a higher carrier
frequency was observed for Hispanic-American individuals (1/48) using the 69
mutation panel as compared with the 32-mutation panel (1/69). The 69-mutation
panel detected ~20% more mutations than the 32-mutation panel for both African
American and Hispanic-American individuals. CONCLUSION: Expanded panels using
race-specific variants can improve cystic fibrosis carrier detection rates within
specific populations. However, it is important that the pathogenicity and the
relative frequency of these variants are confirmed.
PMID- 24357849
TI - Large numbers of individuals are required to classify and define risk for rare
variants in known cancer risk genes.
AB - PURPOSE: Up to half of unique genetic variants in genomic evaluations of familial
cancer risk will be rare variants of uncertain significance. Classification of
rare variants will be an ongoing issue as genomic testing becomes more common.
METHODS: We modified standard power calculations to explore sample sizes
necessary to classify and estimate relative disease risk for rare variant
frequencies (0.001-0.00001) and varying relative risk (20-1.5), using population
based and family-based designs focusing on breast and colon cancer. We required
80% power and tolerated a 10% false-positive rate because variants tested will be
in known genes with high pretest probability. RESULTS: Using population-based
strategies, hundreds to millions of cases are necessary to classify rare cancer
variants. Larger samples are necessary for less frequent and less penetrant
variants. Family-based strategies are robust to changes in variant frequency and
require between 8 and 1,175 individuals, depending on risk. CONCLUSION: It is
unlikely that most rare missense variants will be classifiable in the near
future, and accurate relative risk estimates may never be available for very rare
variants. This knowledge may alter strategies for communicating information about
variants of uncertain significance to patients.
PMID- 24357850
TI - Mining the human genome after Association for Molecular Pathology v. Myriad
Genetics.
AB - The Supreme Court's recent decision in Association for Molecular Pathology v.
Myriad Genetics portrays the human genome as a product of nature. This frames
medical genetics as an extractive industry that mines a natural resource to
produce valuable goods and services. Natural resource law offers insights into
problems medical geneticists can expect after this decision and suggests possible
solutions. Increased competition among clinical laboratories offers various
benefits but threatens to increase fragmentation of genetic data resources,
potentially causing waste in the form of lost opportunities to discover the
clinical significance of particular gene variants. The solution lies in
addressing legal barriers to appropriate data sharing. Sustainable discovery in
the field of medical genetics can best be achieved through voluntary data sharing
rather than command-and-control tactics, but voluntary mechanisms must be
conceived broadly to include market-based approaches as well as donative and
publicly funded data commons. The recently revised Health Insurance Portability
and Accountability Act Privacy Rule offers an improved--but still imperfect-
framework for market-oriented data sharing. This article explores strategies for
addressing the Privacy Rule's remaining defects. America is close to having a
legal framework that can reward innovators, protect privacy, and promote needed
data sharing to advance medical genetics.
PMID- 24357851
TI - Angelina Jolie's faulty gene: newspaper coverage of a celebrity's preventive
bilateral mastectomy in Canada, the United States, and the United Kingdom.
AB - PURPOSE: This study investigates the portrayal of Angelina Jolie's preventive
bilateral mastectomy in the news media. Content analysis of print news was
conducted to identify major frames used in press coverage, the overall tone of
discussions, how journalists report broader questions about BRCA1/2 testing and
hereditary breast/ovarian cancer, and whether they raise concerns about the
impact of celebrities on patients' choices and public opinion. METHODS: The
Factiva database was used to collect publications on Jolie's preventive
mastectomy in elite newspapers in Canada, the United States, and the United
Kingdom. The data set consisted of 103 newspaper articles published in the first
month of media coverage. RESULTS: The results show that although the press
discussed key issues surrounding predictive genetic testing and preventive
options for women at high risk of hereditary breast/ovarian cancer, important
medical information about the rarity of Jolie's condition was not communicated to
the public. CONCLUSION: The results highlight the media's overwhelmingly positive
slant toward Jolie's mastectomy, while overlooking the relative rarity of her
situation, the challenges of "celebrity medicine," and how celebrities influence
people's medical decisions. Future research is required to investigate whether
the media hype has influenced demand and use of BRCA1/2 testing and preventive
mastectomies.
PMID- 24357852
TI - Ex vivo microperfusion system of the adipose organ: a new approach to studying
the mobilization of adipose cell populations.
AB - BACKGROUND/OBJECTIVES: Adipose tissue (AT) is a dynamic organ that expands and
contracts rapidly. It is composed of adipocytes and of cell populations among
which immune cells and mesenchymal progenitors known as adipose stromal cells
(ASCs). The AT cell turnover has been extensively studied. Surprisingly it has
only been viewed as the result of both cell proliferation/death and cell
infiltration. Nevertheless, both immune cells and ASCs exhibit migration
abilities; therefore their egress from AT in response to
physiological/pathophysiological stimuli has to be considered. To do so, the aim
of the present work was to develop a model allowing the study of cell release
from the adipose organ. SUBJECTS/METHODS: Mesenteric (Mes) ATs were isolated from
9-week-old C57BL/6 male mice and were catheterized via the superior mesenteric
artery and were perfused with a saline solution. After an equilibration period,
the mesenteric fat pad was perfused with CXCL12 (stromal-derived factor-1, SDF-1)
or sphingosine 1-phosphate (S1P) to trigger cell mobilization and perfusates were
collected every 30 min for subsequent flow cytometry analyses. RESULTS: We report
here that CXCL12 induces the specific release of ASCs from MesAT thus
demonstrating that ASCs are specifically mobilized from fat depots by a CXCL12
dependent pathway. Moreover, we showed that leukocyte mobilization can be
triggered via a S1P-dependent pathway. CONCLUSIONS: We have developed a
microperfusion model of an intact fat depot allowing the study of AT cell release
in response to various molecules. The perfusion system described here
demonstrates that ASCs and leukocytes can be pharmacologically mobilized from AT.
Therefore, AT microperfusion might constitute an appropriate and reliable
approach for evaluating the mobilization of different cell populations from AT in
various physiological and pathophysiological contexts. Such a model might help in
identifying factors and drugs controlling AT cell release, impacting the medical
fields of regenerative medicine and of obesity or its associated comorbidities.
PMID- 24357853
TI - Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with
visceral adiposity and metabolic syndrome in humans.
AB - BACKGROUND: C1q/TNF-Related Protein (CTRP) family members are novel adipokines
that have anti-inflammatory, immunomodulatory, glucose-regulating and vascular
effects. However, the metabolic effects of CTRP9 remain unclear in humans.
OBJECTIVES: The aims of this study were to investigate whether serum CTRP9
concentrations are associated with glucose tolerance, metabolic parameters and
abdominal fat accumulation. In addition, the authors investigated whether the
aforementioned effects of CTRP9 are independent of serum adiponectin levels.
METHODS: A total of 221 subjects (140 men and 81 women), 25-72 years of age (mean
age 46.0 years), were randomly selected from two different study populations. The
normal glucose tolerance group (n=120) was selected from one study population and
the prediabetes/type 2 diabetes group (n=101) was selected from the other study
population. Serum CTRP9, total adiponectin concentrations and abdominal fat via
computed tomography scan were measured in all subjects. RESULTS: Subjects in the
lower serum CTRP9 tertile were older, had metabolically unhealthy profiles and
had lower serum total adiponectin levels when compared with subjects in the
middle or upper serum CTRP9 tertiles. In addition, serum CTRP9 concentration were
inversely correlated with age, blood pressure, fasting glucose, homeostasis model
assessment for insulin resistance, total cholesterol, triglyceride and low
density lipoprotein cholesterol levels (all P<0.01) and positively correlated
with serum total adiponectin levels (P=0.03). In terms of abdominal fat
accumulation, serum CTRP9 concentrations were inversely correlated with visceral
fat amount (P<0.01), but no correlation was observed with subcutaneous fat
amount. Finally, serum CTRP9 was inversely associated with the presence of
metabolic syndrome, independent of age, sex, body mass index, smoking status,
total cholesterol, visceral fat and serum total adiponectin concentrations (odds
ratio per 1 s.d. 0.47; 95% confidence interval 0.32-0.70; P<0.01). CONCLUSIONS:
Serum CTRP9 concentrations were positively associated with favorable glucose or
metabolic phenotypes and absence of metabolic syndrome, independent of serum
total adiponectin concentrations.
PMID- 24357854
TI - Identification of the involvement of LOXL4 in generation of keratocystic
odontogenic tumors by RNA-Seq analysis.
AB - Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive
intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel
density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify
genes in the stroma of KCOT involved in tumor development and progression, RNA
sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal
fibroblasts isolated from gingival tissues. Seven candidate genes that possess a
function potentially related to KCOT progression were selected and their
expression levels were confirmed by quantitative PCR, immunohistochemistry and
enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4),
the only candidate gene that encodes a secreted protein, was enhanced at both the
mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal
fibroblasts compared to control tissues and primary fibroblasts (P<0.05). In
vitro, high expression of LOXL4 could enhance proliferation and migration of the
human umbilical vein endothelial cells (HUVECs). There was a significant,
positive correlation between LOXL4 protein expression and MVD in stroma of KCOT
and control tissues (r=0.882). These data suggest that abnormal expression of
LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the
locally aggressive biological behavior of KCOT.
PMID- 24357855
TI - Systematic review of mini-implant displacement under orthodontic loading.
AB - A growing number of studies have reported that mini-implants do not remain in
exactly the same position during treatment, although they remain stable. The aim
of this review was to collect data regarding primary displacement immediately
straight after loading and secondary displacement over time. A systematic review
was performed to investigate primary and secondary displacement. The amount and
type of displacement were recorded. A total of 27 studies were included. Sixteen
in vitro studies or studies using finite element analysis addressed primary
displacement, and nine clinical studies and two animal studies addressed
secondary displacement. Significant primary displacement was detected (6.4-24.4
um) for relevant orthodontic forces (0.5-2.5 N). The mean secondary displacement
ranged from 0 to 2.7 mm for entire mini-implants. The maximum values for each
clinical study ranged from 1.0 to 4.1 mm for the head, 1.0 to 1.5 for the body
and 1.0 to 1.92 mm for the tail part. The most frequent type of movement was
controlled tipping or bodily movement. Primary displacement did not reach a
clinically significant level. However, clinicians can expect relevant secondary
displacement in the direction of force. Consequently, decentralized insertion
within the inter-radicular space, away from force direction, might be favourable.
More evidence is needed to provide quantitative recommendations.
PMID- 24357856
TI - Clinical effectiveness of palifermin in prevention and treatment of oral
mucositis in children with acute lymphoblastic leukaemia: a case-control study.
AB - The aim of this study was to evaluate the efficacy of palifermin, an N-terminal
truncated version of endogenous keratinocyte growth factor, in the control of
oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic
stem-cell transplantation for acute lymphoblastic leukaemia were treated with
palifermin, and compared to a control group with the same number of subjects and
similar inclusion criteria. Statistical analysis were performed to compare the
outcomes in the treatment vs. control groups. In the treatment group, we found a
statistically significant reduction in the duration of parenteral nutrition
(P=0.002), duration of mucositis (P=0.003) and the average grade of mucositis
(P=0.03). The statistical analysis showed that the drug was able to decrease the
severity of mucositis. These data, although preliminary, suggest that palifermin
could be a valid therapeutic adjuvant to improve the quality of life of patients
suffering from leukaemia.
PMID- 24357861
TI - Guidelines for youth sports clubs to develop, implement, and assess health
promotion within its activities.
AB - The settings approach to health promotion is a world-known concept concerning
settings like city, hospital, school, and workplace. The concept has also been
used in some regionally specific settings, such as island, prison, or university.
However, there are still many, often noninstitutional, settings that have a lot
of potential but have not yet been recognized. One of the newcomers is the youth
sports club, which has the potential to reach a lot of children and adolescents
and is effective, via its casual educational nature based on voluntary
participation. According to research, health is an important aim for most youth
sports clubs, but it has not been converted into practical actions. Indeed, the
clubs often recognize the importance of healthy lifestyles, but there is a lack
of understanding of what to do to reinforce it within one's activities. That is
why, on the basis of the results of the Health Promoting Sports Club survey in
Finland, guidelines for clubs to enhance health promotion as a part of their
activities were created. The aim of this article is to present the guidelines,
theirs rationale, and practical examples.
PMID- 24357857
TI - Residual activity of cetrimide and chlorhexidine on Enterococcus faecalis
infected root canals.
AB - Effective final irrigation regimen is an important step in order to achieve
better disinfection and ensure residual antimicrobial effects after root canal
preparation. The aim of this study was to compare the residual antimicrobial
activity of 0.2% cetrimide, and 0.2% and 2% chlorhexidine in root canals infected
with Enterococcus faecalis. Biofilms of E. faecalis were grown on uniradicular
roots for 4 weeks. After root canal preparation, root canals were irrigated with
17% ethylenediaminetetraacetic acid (EDTA) to remove the smear layer. The roots
were randomly divided into three experimental groups (n=26) according to the
final irrigating solution: Group I, 5 mL 0.2% cetrimide; Group II, 5 mL 0.2%
chlorhexidine; and Group III, 5 mL 2% chlorhexidine. Samples were collected for
50 days to denote the presence of bacterial growth. The proportion of ungrown
specimens over 50 days was evaluated using the nonparametric Kaplan-Meier
survival analysis. Differences among groups were tested using the log-rank test
and the level of statistical significance was set at P<0.05. The highest survival
value was found with 2% chlorhexidine, showing statistically significant
differences from the other two groups. At 50 days, E. faecalis growth was
detected in 69.23% specimens in Groups I and II, and in 34.61% specimens of Group
III. There were no significant differences between 0.2% cetrimide and 0.2%
chlorhexidine. Final irrigation with 2% chlorhexidine showed greater residual
activity than 0.2% chlorhexidine and 0.2% cetrimide in root canals infected with
E. faecalis.
PMID- 24357862
TI - Key considerations in designing a patient navigation program for colorectal
cancer screening.
AB - Colorectal cancer is the second leading cause of cancer mortality among those
cancers affecting both men and women. Screening is known to reduce mortality by
detecting cancer early and through colonoscopy, removing precancerous polyps.
Only 58.6% of adults are currently up-to-date with colorectal cancer screening by
any method. Patient navigation shows promise in increasing adherence to
colorectal cancer screening and reducing health disparities; however, it is a
complex intervention that is operationalized differently across institutions.
This article describes 10 key considerations in designing a patient navigation
intervention for colorectal cancer screening based on a literature review and
environmental scan. Factors include (1) identifying a theoretical framework and
setting program goals, (2) specifying community characteristics, (3) establishing
the point(s) of intervention within the cancer continuum, (4) determining the
setting in which navigation services are provided, (5) identifying the range of
services offered and patient navigator responsibilities, (6) determining the
background and qualifications of navigators, (7) selecting the method of
communications between patients and navigators, (8) designing the navigator
training, (9) defining oversight and supervision for the navigators, and (10)
evaluating patient navigation. Public health practitioners can benefit from the
practical perspective offered here for designing patient navigation programs.
PMID- 24357863
TI - Assessing media access and use among Latina adolescents to inform development of
a physical activity promotion intervention incorporating text messaging.
AB - Increasing physical activity (PA) during preadolescence and adolescence is
critical to reversing the obesity epidemic. A recent report described the
promising role of eHealth--the use of new media for purposes of health promotion-
in reducing and preventing childhood obesity. This study assessed access/use of
various media (cell phones, computers, gaming systems, Internet) among adolescent
Latino girls and examined the relationship between PA and media access/use. A
convenience sample of 110 Latino girls ages 11 to 14 was recruited from Girl
Scouts of Southwest Texas and other groups. The media survey was self
administered (April-July 2010) on personal digital assistants. Of the girls, 55%
reported owning a cell phone and spending 40 (SD = 4.2) hours per week talking,
texting, listening to music, and browsing the Internet. Cell phone access
increased significantly with age (p = .029). Compared to those with no cell
phone, girls with a cell phone have greater odds of reporting more than 5 days of
PA in the past week (odds ratio = 5.5, 95% confidence interval [CI] = 2.1, 14)
and engaging in daily physical education classes (odds ratio = 2.6, 95% CI = 1.1,
5.9). Since girls with cell phones report greater PA, cell phones may be an
effective strategy for communicating with girls about engaging in PA.
PMID- 24357864
TI - Mediators of adherence among adults with comorbid diabetes and depression: The
role of self-efficacy and social support.
AB - Depression and diabetes have been linked in a variety of ways, and the presence
of depression in those with diabetes can negatively affect adherence to care
recommendations. A sample of 201 participants with Type 2 Diabetes completed a
cross-sectional survey that assessed depressive symptoms, adherence, self
efficacy, social support, and personal characteristics. Multiple regression
analysis was used to test whether self-efficacy and social support mediate the
relationship between depressive symptoms and adherence. The findings suggest
complete mediation via self-efficacy and some types of social support.
Intervening to bolster self-efficacy and social support may decrease the negative
effect of depression on adherence.
PMID- 24357865
TI - Effect of Retention in First Grade on Parents' Educational Expectations and
Children's Academic Outcomes.
AB - The effect of retention in first grade (Year 1) on parents' educational
expectations was tested in a sample of 530 ethnically diverse and academically at
risk children. Participants attended one of three school districts in Texas. Of
the 530 children, 118 were retained in first grade. Retention had a negative
effect on parent expectations in Year 2, which was maintained in Year 3. Year 2
parent expectations partially mediated the effect of retention in first grade on
Year 3 reading and math achievement and child academic self-efficacy. All effects
controlled for Year 1 measures of the outcome. Results were similar across
gender, economic adversity, and ethnicity. Implications for minimizing the
negative effect of retention on parents' expectations are suggested.
PMID- 24357866
TI - Effectiveness of Unfractionated Heparin in Normal Saline versus Dextrose for
Achieving and Maintaining Therapeutic Anti-Factor Xa Levels in Patients with Non
ST-Elevation Acute Coronary Syndrome.
AB - BACKGROUND: Unfractionated heparin (UFH) administered by IV infusion is effective
in preventing myocardial infarction and death after non-ST-elevation acute
coronary syndrome. At the authors' centre, preparations of UFH in 0.9% sodium
chloride (normal saline; UFH-NS) were used during a shortage of commercially
available UFH in dextrose 5% in water (UFH-D5W), the usual preparation. Anecdotal
observations raised concerns about the effectiveness of the saline-based
preparation in achieving minimally therapeutic anticoagulation. OBJECTIVE: To
compare the effectiveness of UFH-NS and UFH-D5W for achieving and maintaining
therapeutic anti-factor Xa levels in patients with non-ST-elevation acute
coronary syndrome. METHODS: A retrospective cohort study was conducted with 2
groups of 100 consecutive patients who received either UFH-NS or UFH-D5W for a
minimum of 24 h after non-ST-elevation acute coronary syndrome in accordance with
a weight-based dosing nomogram. RESULTS: A minimally therapeutic level of anti-Xa
(>= 0.31 IU/mL) was achieved within 24 h for 92% of the patients receiving UFH
D5W and 67% of those receiving UFH-NS (absolute risk difference 25%, 95%
confidence interval [CI] 13.4%-36.6%; p < 0.001). Infusion of UFH-NS was
associated with lower probability of achieving minimally therapeutic
anticoagulation (hazard ratio [HR] 2.30, 95% CI 1.68-3.15; p < 0.001) and
maintaining therapeutic anticoagulation (HR 2.31, 95% CI 1.69-3.17; p < 0.001)
relative to UFH-D5W. Significant differences in the numbers of patients with
subtherapeutic and therapeutic anticoagulation, favouring UFH-D5W, were observed
at each of the first, second, and third anti-Xa measurements (p < 0.05). Patients
receiving UFH-NS required a greater median number of adjustments to the infusion
rate during the first 48 h (1.0 v. 0.5 adjustment per day, p < 0.001). There was
no difference between groups in terms of major reductions in hemoglobin.
CONCLUSIONS: Infusion of UFH-NS was inferior to UFH-D5W for achieving and
maintaining therapeutic anticoagulation in patients with non-ST-elevation acute
coronary syndrome. Until further study, saline-based heparin infusions should be
used with caution, and patients should be monitored closely to ensure timely
achievement and maintenance of therapeutic anticoagulation.
PMID- 24357867
TI - Satisfaction survey for a medication management program: satisfaction guaranteed?
AB - BACKGROUND: Providing clinical pharmacy services to patients in their homes after
discharge from hospital has been reported to reduce health care costs and improve
outcomes. The Medication Management Program of the Fraser Health Authority
involves pharmacists making home visits to provide clinical pharmacy services to
elderly patients who have recently been discharged from hospital and others
considered to be at high risk for adverse drug events. Although clinical and
economic outcomes of this program have been evaluated, humanistic outcomes such
as satisfaction have not been assessed. Moreover, very little evaluation of
patient satisfaction with home pharmacy services has been reported in the
literature. OBJECTIVE: To evaluate patient satisfaction with the Medication
Management Program. METHODS: A telephone survey instrument, consisting of 7
Likert-scale items and 2 open-ended questions, was developed and administered to
patients who received a home pharmacist visit between September 1 and November
23, 2011. In addition to the survey responses, demographic and clinical data for
both respondents and nonrespondents were collected. RESULTS: Of the 175 patients
invited to participate in the survey, 103 (58.9%) agreed to participate. The
majority of respondents agreed or strongly agreed with all of the survey items,
indicating satisfaction with the program. For example, 97 (94%) agreed or
strongly agreed that they would recommend the pharmacist home visit program
continue to be available, and all 103 (100%) agreed or strongly agreed that they
were satisfied with the pharmacist home visit. Respondents provided some
suggestions for program improvement. CONCLUSIONS: The survey findings demonstrate
that patients were satisfied with the home clinical pharmacy services offered
through the Fraser Health Medication Management Program.
PMID- 24357868
TI - Treatment Strategies for Recurrent Clostridium difficile Infection.
AB - BACKGROUND: Recurrent Clostridium difficile infection represents a major clinical
challenge. Treatment is often based on empiric selection from relatively few
options supported by limited clinical evidence. OBJECTIVE: To review and evaluate
the literature on therapeutic alternatives for recurrent C. difficile infection.
DATA SOURCES: The MEDLINE, PubMed, Embase, and Cochrane databases were searched
from inception to 2013 for published evidence in English on the treatment of
recurrent C. difficile infection. The search terms were "Clostridium difficile",
"recurrent" or "relapse", and "treatment". STUDY SELECTION AND DATA EXTRACTION:
Studies of any design were eligible for inclusion. Two reviewers assessed
abstracts, full articles, and reference lists from retrieved articles and
clinical practice guidelines to identify relevant literature. DATA SYNTHESIS: The
evidence to guide treatment of recurrent C. difficile infection is limited, with
24 studies meeting the inclusion criteria for this review. A repeat course of
oral metronidazole or vancomycin is recommended for treatment of mild to moderate
first recurrences and has not been found to influence the likelihood of
subsequent recurrence. Oral vancomycin may be preferred for more severe
infections; however, the severity score warrants further study and validation.
For the treatment of second and subsequent recurrences, tapered or pulsed
vancomycin regimens have been recommended in practice guidelines, despite very
limited clinical evidence. Similarly, the potential benefits of longer treatment
courses of oral vancomycin for second and subsequent recurrences warrant
investigation. The potential role, including costs and benefits, of new agents
such as fidaxomicin in the treatment of recurrent C. difficile infection remains
to be determined. Although there is insufficient evidence to recommend probiotics
as an adjunct to conventional treatment for recurrent infection, there may be
benefit in terms of prevention. CONCLUSIONS: This literature review identified
significant limitations in currently recommended interventions for the treatment
of recurrent C. difficile infection. It has also provided insight into the
available evidence for determining the appropriateness of therapy for patients
with recurrent infection.
PMID- 24357870
TI - [Not Available].
PMID- 24357869
TI - Standards of clinical practice for renal pharmacists.
PMID- 24357871
TI - Exposure to maternal medications: a case of lockjaw.
PMID- 24357872
TI - Trimethoprim-Sulfamethoxazole for Treatment of Stenotrophomonas maltophilia
Pneumonia in a Neonate.
PMID- 24357873
TI - Decreased tacrolimus levels after administration of rifampin to a patient with
renal transplant.
PMID- 24357874
TI - Should dexmedetomidine replace benzodiazepines as the preferred sedative, as
suggested by new guidelines from the society for critical care medicine?
PMID- 24357875
TI - [Not Available].
PMID- 24357876
TI - Closing the loop.
PMID- 24357877
TI - Drug Shortages through the Decades: A Big-Picture Perspective.
PMID- 24357878
TI - [Not Available].
PMID- 24357879
TI - Women's Education, Marital Violence, and Divorce: A Social Exchange Perspective.
AB - Drawing on social exchange theories, the authors hypothesized that educated women
are more likely than uneducated women to leave violent marriages and suggested
that this pattern offsets the negative education - divorce association commonly
found in the United States. They tested these hypotheses using 2 waves of young
adult data on 914 married women from the National Longitudinal Study of
Adolescent Health. The evidence suggests that the negative relationship between
women's education and divorce is weaker when marriages involve abuse than when
they do not. The authors observed a similar pattern when they examined the
association of women's proportional earnings and divorce, controlling for
education. Supplementary analyses suggested that marital satisfaction explains
some of the association among women's resources, victimization, and divorce but
that marital violence continues to be a significant moderator of the education -
divorce association. In sum, education appears to benefit women by both
maintaining stable marriages and dissolving violent ones.
PMID- 24357882
TI - Firing Costs and Flexibility: Evidence from Firms' Employment Responses to Shocks
in India.
AB - A key prediction of dynamic labor demand models is that firing restrictions
attenuate firms' employment responses to economic fluctuations. We provide the
first direct test of this prediction using data from India. We exploit the fact
that rainfall fluctuations, through their effects on agricultural productivity,
generate variation in local demand within districts over time. Consistent with
the theory, we find that industrial employment is more sensitive to shocks where
labor regulation is less restrictive. Our results are robust to controlling for
endogenous firm placement and vary across factory size in a pattern consistent
with institutional features of Indian labor law.
PMID- 24357883
TI - Reduced hierarchical models with application to estimating health effects of
simultaneous exposure to multiple pollutants.
AB - Hierarchical models (HM) have been used extensively in multisite time series
studies of air pollution and health to estimate health effects of a single
pollutant adjusted for other pollutants and other time-varying factors. Recently,
Environmental Protection Agency (EPA) has called for research quantifying health
effects of simultaneous exposure to many air pollutants. However, straightforward
application of HM in this context is challenged by the need to specify a random
effect distribution on a high-dimensional vector of nuisance parameters. Here we
introduce reduced HM as a general statistical approach for analyzing correlated
data with many nuisance parameters. For reduced HM we first calculate the
integrated likelihood of the parameter of interest (e.g. excess number of deaths
attributed to simultaneous exposure to high levels of many pollutants), and we
then specify a flexible random-effect distribution directly on this parameter.
Simulation studies show that the reduced HM performs comparably to the full HM in
many scenarios, and even performs better in some cases, particularly when the
multivariate random-effect distribution of the full HM is misspecified. Methods
are applied to estimate relative risks of cardiovascular hospital admissions
associated with simultaneous exposure to elevated levels of particulate matter
and ozone in 51 US counties during 1999-2005.
PMID- 24357884
TI - Practical Marginalized Multilevel Models.
AB - Clustered data analysis is characterized by the need to describe both systematic
variation in a mean model and cluster-dependent random variation in an
association model. Marginalized multilevel models embrace the robustness and
interpretations of a marginal mean model, while retaining the likelihood
inference capabilities and flexible dependence structures of a conditional
association model. Although there has been increasing recognition of the
attractiveness of marginalized multilevel models, there has been a gap in their
practical application arising from a lack of readily available estimation
procedures. We extend the marginalized multilevel model to allow for nonlinear
functions in both the mean and association aspects. We then formulate marginal
models through conditional specifications to facilitate estimation with mixed
model computational solutions already in place. We illustrate the MMM and
approximate MMM approaches on a cerebrovascular deficiency crossover trial using
SAS and an epidemiological study on race and visual impairment using R. Datasets,
SAS and R code are included as supplemental materials.
PMID- 24357885
TI - N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate as a highly active and selective
esterification catalyst.
AB - N-Butyl-2,4-dinitro-anilinium p-toluenesulfonate (1) was found to be a very
active esterification catalyst that promotes condensation of equal mole amount of
carboxylic acids and alcohols under mild conditions. This catalyst is also highly
selective towards carboxylic acid and alcohol substrates at ambient temperature.
PMID- 24357886
TI - Localizing age-related individual differences in a hierarchical structure.
AB - Data from 33 separate studies were combined to create an aggregate data set
consisting of 16 cognitive variables and 6832 different individuals who ranged
between 18 and 95 years of age. Analyses were conducted to determine where in a
hierarchical structure of cognitive abilities individual differences associated
with age, gender, education, and self-reported health could be localized. The
results indicated that each type of individual difference characteristic
exhibited a different pattern of influences within the hierarchical structure,
and that aging was associated with four statistically distinct influences;
negative influences on a second-order common factor and on first-order speed and
memory factors, and a positive influence on a first-order vocabulary factor.
PMID- 24357887
TI - Predicting Filipino Mothers' and Fathers' Reported Use of Corporal Punishment
From Education, Authoritarian Attitudes, and Endorsement of Corporal Punishment.
AB - The relations of education, authoritarian childrearing attitudes, and endorsement
of corporal punishment to Filipino parents' reported use of corporal punishment
were examined using two waves of data. Structured interviews using self-report
questionnaires were conducted with 117 mothers and 98 fathers from 120 families
when their children were 8 years old, and when their children were 9 years old.
Path analyses showed that, among mothers, higher education predicted lower
authoritarian attitudes, which in turn predicted lower reports of corporal
punishment use. Among fathers, higher education predicted lower endorsement of
corporal punishment, which in turn predicted lower reports of its use. Results
suggest that education has an indirect relation to use of corporal punishment
through parenting cognitions, and highlight distinctions in Filipino mothers' and
fathers' parenting roles.
PMID- 24357888
TI - How can social network analysis contribute to social behavior research in applied
ethology?
AB - Social network analysis is increasingly used by behavioral ecologists and
primatologists to describe the patterns and quality of interactions among
individuals. We provide an overview of this methodology, with examples
illustrating how it can be used to study social behavior in applied contexts.
Like most kinds of social interaction analyses, social network analysis provides
information about direct relationships (e.g. dominant-subordinate relationships).
However, it also generates a more global model of social organization that
determines how individual patterns of social interaction relate to individual and
group characteristics. A particular strength of this approach is that it provides
standardized mathematical methods for calculating metrics of sociality across
levels of social organization, from the population and group levels to the
individual level. At the group level these metrics can be used to track changes
in social network structures over time, evaluate the effect of the environment on
social network structure, or compare social structures across groups, populations
or species. At the individual level, the metrics allow quantification of the
heterogeneity of social experience within groups and identification of
individuals who may play especially important roles in maintaining social
stability or information flow throughout the network.
PMID- 24357889
TI - High spectral and spatial resolution X-ray transmission radiography and
tomography using a Color X-ray Camera.
AB - High resolution X-ray radiography and computed tomography are excellent
techniques for non-destructive characterization of an object under investigation
at a spatial resolution in the micrometer range. However, as the image contrast
depends on both chemical composition and material density, no chemical
information is obtained from this data. Furthermore, lab-based measurements are
affected by the polychromatic X-ray beam, which results in beam hardening
effects. New types of X-ray detectors which provide spectral information on the
measured X-ray beam can help to overcome these limitations. In this paper, an
energy dispersive CCD detector with high spectral resolution is characterized for
use in high resolution radiography and tomography, where a focus is put on the
experimental conditions and requirements of both measurement techniques.
PMID- 24357890
TI - An adaptive coarse graining method for signal transduction in three dimensions.
AB - The spatio-temporal landscape of the plasma membrane regulates activation and
signal transduction of membrane bound receptors by restricting their two
dimensional mobility and by inducing receptor clustering. This regulation also
extends to complex formation between receptors and adaptor proteins, which are
the intermediate signaling molecules involved in cellular signaling that relay
the received cues from cell surface to cytoplasm and eventually to the nucleus.
Although their investigation poses challenging technical difficulties, there is a
crucial need to understand the impact of the receptor diffusivity, clustering,
and spatial heterogeneity, and of receptor-adaptor protein complex formation on
the cellular signal transduction patterns. Building upon our earlier studies, we
have developed an adaptive coarse-grained Monte Carlo method that can be used to
investigate the role of diffusion, clustering and membrane corralling on receptor
association and receptor-adaptor protein complex formation dynamics in three
dimensions. The new Monte Carlo lattice based approach allowed us to introduce
spatial resolution on the 2-D plasma membrane and to model the cytoplasm in three
dimensions. Being a multi-resolution approach, our new method makes it possible
to represent various parts of the cellular system at different levels of detail
and enabled us to utilize the locally homogeneous assumption when justified
(e.g., cytoplasmic region away from the cell membrane) and avoid its use when
high spatial resolution is needed (e.g., cell membrane and cytoplasmic region
near the membrane) while keeping the required computational complexity
manageable. Our results have shown that diffusion has a significant impact on
receptor-receptor dimerization and receptor-adaptor protein complex formation
kinetics. We have observed an "adaptor protein hopping" mechanism where the
receptor binding proteins may hop between receptors to form short-lived transient
complexes. This increased residence time of the adaptor proteins near cell
membrane and their ability to frequently change signaling partners may explain
the increase in signaling efficiency when receptors are clustered. We also
hypothesize that the adaptor protein hopping mechanism can cause concurrent or
sequential activation of multiple signaling pathways, thus leading to crosstalk
between diverse biological functions.
PMID- 24357891
TI - Randomized Trial of Promoting First Relationships: Effects on Maltreated
Toddlers' Separation Distress and Sleep Regulation after Reunification.
AB - This study investigates the impact of an attachment focused intervention,
Promoting First Relationships (PFR), on sleep problems among toddlers in child
welfare recently reunified with their birth parent. Recently reunified parent
toddler dyads (n = 43) were drawn from a larger random control trial. Toddlers
(11-36 months) and their parents were assessed in two-hour research home visits
at enrollment (baseline), and a 6-month post-intervention follow-up. Measures
included parental report of sleep problems and research visitor observation of
separation distress (using the Toddler Attachment Sort-45). The PFR intervention
predicted fewer sleep problems, adjusting for a baseline measure of sleep
problems and other covariates. A path model showed evidence of an indirect effect
of PFR on sleep problems through declines in separation distress. An attachment
focused intervention like PFR that reduces infant separation distress can lead to
reductions in sleep problems.
PMID- 24357893
TI - Fatherhood Across Two Generations Factors Affecting Early Family Roles.
AB - This article examines the determinants of men's early parental roles,
distinguishing factors that affect being a father versus being childless, and
factors that affect being a resident versus a nonresident father, in the context
of having a partner or not. We also consider whether these patterns have changed
between 1985 and 2004. The data come from the linked Child-Mother and Young Adult
Samples of the National Longitudinal Survey of Youth 1979 (NLSY79), which provide
information on the children of the NLSY79 from birth until they enter young
adulthood, and from the original youth sample of parallel ages. The results
support previous research showing the importance of economic and educational
disadvantages and nontraditional family structure on being a non-resident father.
The effects of family structure appear to have attenuated between generations as
determinants of men's early parental roles.
PMID- 24357892
TI - Personality Change at Mid-Life is Associated with Changes in Self-Rated Health:
Evidence from the Hawaii Personality and Health Cohort.
AB - Personality traits change across the lifespan, and trait change, in addition to
trait level, may be related to health. Longitudinal data from the Hawaii
Personality and Health Cohort were used to investigate associations between
changes in traits and self-rated health (SRH). Participants (N = 733, Mage =
44.4) completed measures of the Big Five personality traits and SRH twice
approximately 3 years apart. Personality trait changes were associated with SRH
change. Additionally, increases on Agreeableness, Conscientiousness, and
Openness, and decreases on Neuroticism, predicted increases in SRH, even when
controlling for gender and education. Relating correlated trait change at mid
life, when traits reach peak stability, to a consequential health outcome such as
SRH change, demonstrates the value of treating both traits and health indicators
as dynamic variables.
PMID- 24357894
TI - A Validation of the Inventory of Callous-Unemotional Traits in a Community Sample
of Young Adult Males.
AB - Callous-unemotional (CU) traits have been shown to delineate a subgroup of
individuals at high risk for exhibiting severe and persistent criminal behavior.
The Inventory of Callous-Unemotional Traits (ICU; Frick 2004) was recently
developed as a comprehensive rating scale designed to measure multiple facets of
CU traits. However, validation of this measure has been limited to youth in
adolescence and emerging adulthood (age range=12-20), leaving questions about the
utility of this measure in early adulthood unanswered. The current study
evaluated the factor structure of the ICU within a racially diverse and well
characterized community sample of adult males (n=425) using exploratory factor
analysis (EFA) and confirmatory factor analysis (CFA). While results found the
best fitting model to be the three-bifactor structure that has been previously
reported in adolescent samples, the fit indices were only marginally acceptable
and suggest the need for scale refinement. Total and subscales scores
demonstrated significant and distinct associations with relevant external
criteria (e.g., delinquency, psychopathy, psychopathology, psychosocial
functioning). Implications and directions for future research are discussed.
PMID- 24357895
TI - TRANSPORT AND FATE OF AMMONIUM AND ITS IMPACT ON URANIUM AND OTHER TRACE ELEMENTS
AT A FORMER URANIUM MILL TAILING SITE.
AB - The remediation of ammonium-containing groundwater discharged from uranium mill
tailing sites is a difficult problem facing the mining industry. The Monument
Valley site is a former uranium mining site in the southwest US with both
ammonium and nitrate contamination of groundwater. In this study, samples
collected from 14 selected wells were analyzed for major cations and anions,
trace elements, and isotopic composition of ammonium and nitrate. In addition,
geochemical data from the U.S. Department of Energy (DOE) database were analyzed.
Results showing oxic redox conditions and correspondence of isotopic compositions
of ammonium and nitrate confirmed the natural attenuation of ammonium via
nitrification. Moreover, it was observed that ammonium concentration within the
plume area is closely related to concentrations of uranium and a series of other
trace elements including chromium, selenium, vanadium, iron, and manganese. It is
hypothesized that ammonium-nitrate transformation processes influence the
disposition of the trace elements through mediation of redox potential, pH, and
possibly aqueous complexation and solid-phase sorption. Despite the generally
relatively low concentrations of trace elements present in groundwater, their
transport and fate may be influenced by remediation of ammonium or nitrate at the
site.
PMID- 24357896
TI - Evidence for a relation between executive function and pretense representation in
preschool children.
AB - Several theoretical formulations suggest a relation between children's pretense
and executive function (EF) skills. However, there is little empirical evidence
for a correlation between these constructs in early development. Preschool
children (N = 104; M age = 4-0) were given batteries of EF and pretense
representation measures, as well as verbal, memory, and appearance-reality
control tasks. Confirmatory factor analysis revealed two separable but
overlapping aspects of EF (Conflict and Delay). EF was significantly related to
pretense after accounting for all controls. Understanding the pretend-reality
distinction was strongly related to Conflict EF, whereas performing pretend
actions was more strongly related to Delay EF. These results, although
correlational, are consistent with the claim that EF skills are implicated in
pretense, such as inhibiting reality and flexibly manipulating dual
representations, and offer a potential mechanism by which pretend play
interventions may enhance childhood EF.
PMID- 24357897
TI - Microfluidic Valves Made From Polymerized Polyethylene Glycol Diacrylate.
AB - Pneumatically actuated, non-elastomeric membrane valves fabricated from
polymerized polyethylene glycol diacrylate (poly-PEGDA) have been characterized
for temporal response, valve closure, and long-term durability. A ~100 ms valve
opening time and a ~20 ms closure time offer valve operation as fast as 8 Hz with
potential for further improvement. Comparison of circular and rectangular valve
geometries indicates that the surface area for membrane interaction in the valve
region is important for valve performance. After initial fabrication, the fluid
pressure required to open a closed circular valve is ~50 kPa higher than the
control pressure holding the valve closed. However, after ~1000 actuations to
reconfigure polymer chains and increase elasticity in the membrane, the fluid
pressure required to open a valve becomes the same as the control pressure
holding the valve closed. After these initial conditioning actuations, poly-PEGDA
valves show considerable robustness with no change in effective operation after
115,000 actuations. Such valves constructed from non-adsorptive poly-PEGDA could
also find use as pumps, for application in small volume assays interfaced with
biosensors or impedance detection, for example.
PMID- 24357898
TI - Mediating the intersections of organizational routines during the introduction of
a health IT system.
AB - Public interest in the quality and safety of health care has spurred examination
of specific organizational routines believed to yield risk in health care work.
Medication administration routines, in particular, have been the subject of
numerous improvement projects involving information technology development, and
other forms of research and regulation. This study draws from ethnographic
observation to examine how the common routine of medication administration
intersects with other organizational routines, and why understanding such
intersections is important. We present three cases describing intersections
between medication administration and other routines, including a pharmacy
routine, medication administration on the next shift and management reporting. We
found that each intersection had ostensive and performative dimensions; and
furthermore, that IT-enabled changes to one routine led to unintended
consequences in its intersection with others, resulting in misalignment of
ostensive and performative aspects of the intersection. Our analysis focused on
the activities of a group of nurses who provide technology use mediation (TUM)
before and after the rollout of a new health IT system. This research offers new
insights on the intersection of organizational routines, demonstrates the value
of analyzing TUM activities to better understand the relationship between IT
introduction and changes in routines, and has practical implications for the
implementation of technology in complex practice settings.
PMID- 24357899
TI - Tomographic Reconstruction of Band-limited Hermite Expansions.
AB - In this work, we investigate the parallel-beam projection and reconstruction of
band-limited Hermite expansions. Using a recently developed coordinate conversion
technique, we show how the Fourier slice theorem can be directly applied. In our
new approach, we do not introduce a non-integrable filter that appears in the
filtered backprojection method. Since a projection of a 2D band-limited Hermite
expansion is a 1D band-limited Hermite expansion and the coordinate conversion
technique is lossless with this special expansion, we can avoid a series of
approximations that the classical tomography techniques make.
PMID- 24357900
TI - Dynamic quantitative phase images of pond life, insect wings, and in vitro cell
cultures.
AB - This paper presents images and data of live biological samples taken with a novel
Linnik interference microscope. The specially designed optical system enables
instantaneous and 3D video measurements of dynamic motions within and among live
cells without the need for contrast agents. This "label-free", vibration
insensitive imaging system enables measurement of biological objects in
reflection using harmless light levels with current magnifications of 10X (NA
0.3) and 20X (NA 0.5) and wavelengths of 660 nm and 785 nm over fields of view
from several hundred microns up to a millimeter. At the core of the instrument is
a phase-measurement camera (PMC) enabling simultaneous measurement of multiple
interference patterns utilizing a pixelated phase mask taking advantage of the
polarization properties of light. Utilizing this technology enables the creation
of phase image movies in real time at video rates so that dynamic motions and
volumetric changes can be tracked. Objects are placed on a reflective surface in
liquid under a coverslip. Phase values are converted to optical thickness data
enabling volumetric, motion and morphological studies. Data from a number of
different mud puddle organisms such as paramecium, flagellates and rotifers will
be presented, as will measurements of flying ant wings and cultures of human
breast cancer cells. These data highlight examples of monitoring different
biological processes and motions. The live presentation features 4D phase movies
of these examples.
PMID- 24357901
TI - Dynamic phase imaging utilizing a 4-dimensional microscope system.
AB - This paper describes a new, novel interference Linnik microscope system and
presents images and data of live biological samples. The specially designed
optical system enables instantaneous 4-dimensional video measurements of dynamic
motions within and among live cells without the need for contrast agents. This
"label-free", vibration insensitive imaging system enables measurement of
biological objects in reflection using harmless light levels with a variety of
magnifications and wavelengths with fields of view from several hundred microns
up to a millimeter. At the core of the instrument is a phase measurement camera
(PMC) enabling simultaneous measurement of multiple interference patterns
utilizing a pixelated phase mask taking advantage of the polarization properties
of light. Utilizing this technology enables the creation of phase image movies in
real time at video rates so that dynamic motions and volumetric changes can be
tracked. Objects are placed on a reflective surface in liquid under a coverslip.
Phase values are converted to optical thickness data enabling volumetric, motion
and morphological studies. Data from a number of different organisms such as
flagellates and rotifers will be presented, as will measurements of human breast
cancer cells with the addition of various agents that break down the cells. These
data highlight examples of monitoring different biological processes and motions.
PMID- 24357902
TI - Graphical User Interface for a Dual-Module EMCCD X-ray Detector Array.
AB - A new Graphical User Interface (GUI) was developed using Laboratory Virtual
Instrumentation Engineering Workbench (LabVIEW) for a high-resolution, high
sensitivity Solid State X-ray Image Intensifier (SSXII), which is a new x-ray
detector for radiographic and fluoroscopic imaging, consisting of an array of
Electron-Multiplying CCDs (EMCCDs) each having a variable on-chip electron
multiplication gain of up to 2000* to reduce the effect of readout noise. To
enlarge the field-of-view (FOV), each EMCCD sensor is coupled to an x-ray
phosphor through a fiberoptic taper. Two EMCCD camera modules are used in our
prototype to form a computer-controlled array; however, larger arrays are under
development. The new GUI provides patient registration, EMCCD module control,
image acquisition, and patient image review. Images from the array are stitched
into a 2k*1k pixel image that can be acquired and saved at a rate of 17 Hz
(faster with pixel binning). When reviewing the patient's data, the operator can
select images from the patient's directory tree listed by the GUI and cycle
through the images using a slider bar. Commonly used camera parameters including
exposure time, trigger mode, and individual EMCCD gain can be easily adjusted
using the GUI. The GUI is designed to accommodate expansion of the EMCCD array to
even larger FOVs with more modules. The high-resolution, high-sensitivity EMCCD
modular-array SSXII imager with the new user-friendly GUI should enable
angiographers and interventionalists to visualize smaller vessels and
endovascular devices, helping them to make more accurate diagnoses and to perform
more precise image-guided interventions.
PMID- 24357903
TI - Fiberoptic metal detector capable of profile detection.
AB - The purpose of this paper is to develop a novel ferromagnetic polymeric metal
detector system by using a fiber-optic Mach-Zehnder interferometer with a newly
developed ferromagnetic polymer as the magnetostrictive sensing device. This
ferromagnetic polymeric metal detector system is simple to fabricate, small in
size, and resistant to RF interference (which is common in typical
electromagnetic type metal detectors). Metal detection is made possible by
disrupting the magnetic flux density present on the magnetostrictive sensor. This
paper discusses the magnetic properties of the ferromagnetic polymers. In
addition, the preliminary results of successful sensing of different geometrical
metal shapes will be discussed.
PMID- 24357904
TI - Remineralization of Root Caries Monitored Using Cross-Polarization Optical
Coherence Tomography.
AB - Previous studies have demonstrated that polarization sensitive optical coherence
tomography (PS-OCT) can be used to image caries lesions in dentin, measure
nondestructively the severity of dentin demineralization, and determine the
efficacy of intervention with anticaries agents including fluoride and lasers.
However, those studies were limited to artificial lesions on dentin and roots
surfaces. The objective of this study is to determine if a cross polarization OCT
system (CP-OCT) can be used to nondestructively measure a reduction in the
reflectivity of natural root caries lesions after exposure to a remineralization
solution. CP-OCT images of 11 teeth with existing root lesions were acquired
before and after exposure to a remineralizing solution for 20 days. The
integrated reflectivity was calculated after integrating to a fixed depth of 200
um. There was a significant decrease in the integrated reflectivity after
exposure to the remineralizing solution.
PMID- 24357905
TI - Monitoring tooth demineralization using a cross polarization optical coherence
tomographic system with an integrated MEMS scanner.
AB - New methods are needed for the nondestructive measurement of tooth
demineralization and remineralization to monitor the progression of incipient
caries lesions (tooth decay) for effective nonsurgical intervention and to
evaluate the performance of anti-caries treatments such as chemical treatments or
laser irradiation. Studies have shown that optical coherence tomography (OCT) has
great potential to fulfill this role since it can be used to measure the depth
and severity of early lesions with an axial resolution exceeding 10-um, it is
easy to apply in vivo and it can be used to image the convoluted topography of
tooth occlusal surfaces. In this paper we present early results using a new cross
polarization OCT system introduced by Santec. This system utilizes a swept laser
source and a MEMS scanner for rapid acquisition of cross polarization images.
Preliminary studies show that this system is useful for measurement of the
severity of demineralization on tooth surfaces and for showing the spread of
occlusal lesions under the dentinal-enamel junction.
PMID- 24357906
TI - Selective Removal of Demineralization Using Near Infrared Cross Polarization
Reflectance and a Carbon Dioxide Laser.
AB - Lasers can ablate/remove tissue in a non-contact mode of operation and a pulsed
laser beam does not interfere with the ability to image the tooth surface,
therefore lasers are ideally suited for integration with imaging devices for
image-guided ablation. Laser energy can be rapidly and efficiently delivered to
tooth surfaces using a digitally controlled laser beam scanning system for
precise and selective laser ablation with minimal loss of healthy tissues. Under
the appropriate irradiation conditions such laser energy can induce beneficial
chemical and morphological changes in the walls of the drilled cavity that can
increase resistance to further dental decay and produce surfaces with enhanced
adhesive properties to restorative materials. Previous studies have shown that
images acquired using near-IR transillumination, optical coherence tomography and
fluorescence can be used to guide the laser for selective removal of
demineralized enamel. Recent studies have shown that NIR reflectance measurements
at 1470-nm can be used to obtain images of enamel demineralization with very high
contrast. The purpose of this study was to demonstrate that image guided ablation
of occlusal lesions can be successfully carried out using a NIR reflectance
imaging system coupled with a carbon dioxide laser operating at 9.3-MUm with high
pulse repetition rates.
PMID- 24357907
TI - Toward the Use of Two-Color Emission Control in Upconverting NaYF4:Er3+, Yb3+
Nanoparticles for Biomedical Imaging.
AB - In the interest of generating new biomedical sensing techniques as well as
improving those that currently exist, a great deal of attention has been given to
upconverting lanthanide nanoparticles in recent years. In order to develop these
nanoparticles for use in multiplexed and ratiometric sensing techniques, many
recent studies have focused on experimental control of their emission
wavelengths. Here we describe a new method for controlling the relative intensity
of green and red emission bands in NaYF4:Yb3+, Er3+ nanoparticles via control of
the excitation pulse repetition rate. Using this method, particles of the same
composition may be tuned to produce red and green light in user-defined ratios.
We discuss the mechanism behind this control as well as potential applications
that could make use of this property, specifically in super resolution imaging
techniques.
PMID- 24357908
TI - Significance of Including Field Non-Uniformities Such as the Heel Effect and Beam
Scatter in the Determination of the Skin Dose Distribution during Interventional
Fluoroscopic Procedures.
AB - The current version of the real-time skin-dose-tracking system (DTS) we have
developed assumes the exposure is contained within the collimated beam and is
uniform except for inverse-square variation. This study investigates the
significance of factors that contribute to beam non-uniformity such as the heel
effect and backscatter from the patient to areas of the skin inside and outside
the collimated beam. Dose-calibrated Gafchromic film (XR-RV3, ISP) was placed in
the beam in the plane of the patient table at a position 15 cm tube-side of
isocenter on a Toshiba Infinix C-Arm system. Separate exposures were made with
the film in contact with a block of 20-cm solid water providing backscatter and
with the film suspended in air without backscatter, both with and without the
table in the beam. The film was scanned to obtain dose profiles and comparison of
the profiles for the various conditions allowed a determination of field non
uniformity and backscatter contribution. With the solid-water phantom and with
the collimator opened completely for the 20-cm mode, the dose profile decreased
by about 40% on the anode side of the field. Backscatter falloff at the beam edge
was about 10% from the center and extra-beam backscatter decreased slowly with
distance from the field, being about 3% of the beam maximum at 6 cm from the
edge. Determination of the magnitude of these factors will allow them to be
included in the skin-dose-distribution calculation and should provide a more
accurate determination of peak-skin dose for the DTS.
PMID- 24357909
TI - Simultaneous Segmentation and Statistical Label Fusion.
AB - Labeling or segmentation of structures of interest in medical imaging plays an
essential role in both clinical and scientific understanding. Two of the common
techniques to obtain these labels are through either fully automated segmentation
or through multi-atlas based segmentation and label fusion. Fully automated
techniques often result in highly accurate segmentations but lack the robustness
to be viable in many cases. On the other hand, label fusion techniques are often
extremely robust, but lack the accuracy of automated algorithms for specific
classes of problems. Herein, we propose to perform simultaneous automated
segmentation and statistical label fusion through the reformulation of a
generative model to include a linkage structure that explicitly estimates the
complex global relationships between labels and intensities. These relationships
are inferred from the atlas labels and intensities and applied to the target
using a non-parametric approach. The novelty of this approach lies in the
combination of previously exclusive techniques and attempts to combine the
accuracy benefits of automated segmentation with the robustness of a multi-atlas
based approach. The accuracy benefits of this simultaneous approach are assessed
using a multi-label multi- atlas whole-brain segmentation experiment and the
segmentation of the highly variable thyroid on computed tomography images. The
results demonstrate that this technique has major benefits for certain types of
problems and has the potential to provide a paradigm shift in which the lines
between statistical label fusion and automated segmentation are dramatically
blurred.
PMID- 24357910
TI - Automating PACS Quality Control with the Vanderbilt Image Processing Enterprise
Resource.
AB - Precise image acquisition is an integral part of modern patient care and medical
imaging research. Periodic quality control using standardized protocols and
phantoms ensures that scanners are operating according to specifications, yet
such procedures do not ensure that individual datasets are free from corruption
for example due to patient motion, transient interference, or physiological
variability. If unacceptable artifacts are noticed during scanning, a
technologist can repeat a procedure. Yet, substantial delays may be incurred if a
problematic scan is not noticed until a radiologist reads the scans or an
automated algorithm fails. Given scores of slices in typical three-dimensional
scans and wide-variety of potential use cases, a technologist cannot practically
be expected inspect all images. In large-scale research, automated pipeline
systems have had great success in achieving high throughput. However, clinical
and institutional workflows are largely based on DICOM and PACS technologies;
these systems are not readily compatible with research systems due to security
and privacy restrictions. Hence, quantitative quality control has been relegated
to individual investigators and too often neglected. Herein, we propose a
scalable system, the Vanderbilt Image Processing Enterprise Resource-VIPER, to
integrate modular quality control and image analysis routines with a standard
PACS configuration. This server unifies image processing routines across an
institutional level and provides a simple interface so that investigators can
collaborate to deploy new analysis technologies. VIPER integrates with high
performance computing environments has successfully analyzed all standard scans
from our institutional research center over the course of the last 18 months.
PMID- 24357911
TI - Imaging Early Demineralization on Tooth Occlusal Surfaces with a High Definition
InGaAs Camera.
AB - In vivo and in vitro studies have shown that high contrast images of tooth
demineralization can be acquired in the near-IR due to the high transparency of
dental enamel. The purpose of this study is to compare the lesion contrast in
reflectance at near-IR wavelengths coincident with high water absorption with
those in the visible, the near-IR at 1300-nm and with fluorescence measurements
for early lesions in occlusal surfaces. Twenty-four human molars were used in
this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a
4*4 mm window in the occlusal surface of each tooth exposed for demineralization.
Artificial lesions were produced in the exposed windows after 1 & 2-day exposure
to a demineralizing solution at pH 4.5. Lesions were imaged using NIR reflectance
at 3 wavelengths, 1310, 1460 and 1600-nm using a high definition InGaAs camera.
Visible light reflectance, and fluorescence with 405-nm excitation and detection
at wavelengths greater than 500-nm were also used to acquire images for
comparison. Crossed polarizers were used for reflectance measurements to reduce
interference from specular reflectance. The contrast of both the 24 hr and 48 hr
lesions were significantly higher (P<0.05) for NIR reflectance imaging at 1460-nm
and 1600-nm than it was for NIR reflectance imaging at 1300-nm, visible
reflectance imaging, and fluorescence. The results of this study suggest that NIR
reflectance measurements at longer near-IR wavelengths coincident with higher
water absorption are better suited for imaging early caries lesions.
PMID- 24357912
TI - Design of a Swept-Source, Anatomical OCT System for Pediatric Bronchoscopy.
AB - We describe the design and performance of a long coherence length, swept-source
anatomical OCT (aOCT) system for pediatric airway imaging. A fiber-optic catheter
is designed to be accommodated by a small-bore bronchoscope, and is scanned
distally in a helical scan pattern to provide aOCT during bronchoscopy. We
discuss particular challenges associated with the need for large imaging range,
low SNR roll-off, and small catheter diameter. We present 3-D visualizations of
airway phantoms and discuss optimization of the airway surface geometry obtained
by aOCT. Accurate reconstruction of airway geometry will enable predictive
modeling of patients suffering from airway obstruction.
PMID- 24357913
TI - A 48-pixel array of Single Photon Avalanche Diodes for multispot Single Molecule
analysis.
AB - In this paper we present an array of 48 Single Photon Avalanche Diodes (SPADs)
specifically designed for multispot Single Molecule Analysis. The detectors have
been arranged in a 12*4 square geometry with a pitch-to-diameter ratio of ten in
order to minimize the collection of the light from non-conjugated excitation
spots. In order to explore the trade-offs between the detectors' performance and
the optical coupling with the experimental setup, SPADs with an active diameter
of 25 and of 50um have been manufactured. The use of a custom technology,
specifically designed for the fabrication of the detectors, allowed us to combine
a high photon detection efficiency (peak close to 50% at a wavelength of 550nm)
with a low dark count rate compatible with true single molecule detection. In
order to allow easy integration into the optical setup for parallel single
molecule analysis, the SPAD array has been incorporated in a compact module
containing all the electronics needed for a proper operation of the detectors.
PMID- 24357914
TI - Software-based Diffusion MR Human Brain Phantom for Evaluating Fiber-tracking
Algorithms.
AB - Fiber tracking provides insights into the brain white matter network and has
become more and more popular in diffusion MR imaging. Hardware or software
phantom provides an essential platform to investigate, validate and compare
various tractography algorithms towards a "gold standard". Software phantoms
excel due to their flexibility in varying imaging parameters, such as tissue
composition, SNR, as well as potential to model various anatomies and
pathologies. This paper describes a novel method in generating diffusion MR
images with various imaging parameters from realistically appearing, individually
varying brain anatomy based on predefined fiber tracts within a high-resolution
human brain atlas. Specifically, joint, high resolution DWI and structural MRI
brain atlases were constructed with images acquired from 6 healthy subjects (age
22-26) for the DWI data and 56 healthy subject (age 18-59) for the structural MRI
data. Full brain fiber tracking was performed with filtered, two-tensor
tractography in atlas space. A deformation field based principal component model
from the structural MRI as well as unbiased atlas building was then employed to
generate synthetic structural brain MR images that are individually varying.
Atlas fiber tracts were accordingly warped into each synthetic brain anatomy.
Diffusion MR images were finally computed from these warped tracts via a
composite hindered and restricted model of diffusion with various imaging
parameters for gradient directions, image resolution and SNR. Furthermore, an
open-source program was developed to evaluate the fiber tracking results both
qualitatively and quantitatively based on various similarity measures.
PMID- 24357915
TI - Stochastic Image Registration with User Constraints.
AB - Constrained registration is an active area of research and is the focus of this
work. This note describes a non-rigid image registration framework for
incorporating landmark constraints. Points that must remain stationary are
selected, the user chooses the spatial extent of the inputs, and an automatic
step computes the deformable registration, respecting the constraints.
Parametrization of the deformation field is by an additive composition of a
similarity transformation and a set of Gaussian radial basis functions. The
bases' centers, variances, and weights are determined with a global optimization
approach that is introduced. This approach is based on the particle filter for
performing constrained optimization; it explores a series of states defining a
deformation field that is physically meaningful (i.e., invertible) and prevents
chosen points from moving. Results on synthetic two dimensional images are
presented.
PMID- 24357916
TI - Cortical Correspondence via Sulcal Curve-Constrained Spherical Registration with
Application to Macaque Studies.
AB - In this work, we present a novel cortical correspondence method with application
to the macaque brain. The correspondence method is based on sulcal curve
constraints on a spherical deformable registration using spherical harmonics to
parameterize the spherical deformation. Starting from structural MR images, we
first apply existing preprocessing steps: brain tissue segmentation using the
Automatic Brain Classification tool (ABC), as well as cortical surface
reconstruction and spherical parametrization of the cortical surface via
Constrained Laplacian-based Automated Segmentation with Proximities (CLASP).
Then, initial correspondence between two cortical surfaces is automatically
determined by a curve labeling method using sulcal landmarks extracted along
sulcal fundic regions. Since the initial correspondence is limited to sulcal
regions, we use spherical harmonics to extrapolate and regularize this
correspondence to the entire cortical surface. To further improve the
correspondence, we compute a spherical registration that optimizes the spherical
harmonic parameterized deformation using a metric that incorporates the error
over the sulcal landmarks as well as the normalized cross correlation of sulcal
depth maps over the whole cortical surface. For evaluation, a normal 18-months
old macaque brain (for both left and right hemispheres) was matched to a prior
macaque brain template with 9 manually labeled, major sulcal curves. The results
show successful registration using the proposed registration approach. Evaluation
results for optimal parameter settings are presented as well.
PMID- 24357917
TI - Minor Illnesses, Temperament, and Toddler Social Functioning.
AB - RESEARCH FINDINGS: Minor illnesses, such as upper respiratory infections,
stomachaches, and fevers, have been associated with children's decreased activity
and increased irritability. Mothers of children who are frequently ill report
more child behavior problems; however, previous research in this area has yet to
simultaneously examine children's temperament. This investigation examined
whether experience with recurrent, minor illnesses and negative emotionality
worked together to predict young children's social functioning. This multi-method
study utilized a sample of 110 daycare-attending children. Nurses went to the
daycare centers weekly to perform health screens on the participating children.
Minor illness experience was represented using a proportion created by dividing
the number of illness diagnoses by the total number of health screenings
completed from the time the child was enrolled in the study through his or her
second birthday. Toddlers' negative emotionality and social behavior were
assessed using mothers' and fathers' reports. The two dimensions of negative
emotionality and minor illness experience operated in different ways such that
anger worked additively with minor illness experience and fearfulness interacted
with minor illness experience to predict social behavior. Children who were
described as more temperamentally angry displayed less social competence
especially when they also experienced high proportions of minor illness.
Temperamentally fearful children exhibited more externalizing problems when they
experienced a higher frequency of illness whereas fearfulness was not associated
to externalizing problems for children who experienced low proportions of
illness. PRACTICE OR POLICY: Children's frequent experience with minor illnesses
combined with negative emotionality appears to place toddlers at a heightened
risk for exhibiting behavior problems. These findings have implications for child
and family well-being as well as interactions with childcare providers and peers
within childcare settings. Interventions could be developed to target "at risk"
children.
PMID- 24357918
TI - Habit Reversal Therapy for Body-Focused Repetitive Behaviors in Williams
Syndrome: A Case Study.
AB - Williams syndrome (WS) is genetic neurodevelopmental disorder with a well
characterized cognitive and behavioral phenotype. Research has consistently
demonstrated high rates of psychopathology in this population; however, little
research has examined the use of empirically-supported psychosocial interventions
in those with WS. The current case study reports on the use of Habit Reversal
Therapy (HRT) to treat multiple body-focused repetitive behaviors in a child with
WS. Although HRT is a well-established cognitive-behavioral intervention for body
focused repetitive behaviors, it has been infrequently used in populations with
developmental disabilities. An etiologically-informed approach was used to adapt
HRT to fit the known behavioral and cognitive phenotype of WS. Results suggest
that HRT may be beneficial for this population. Modified treatment elements are
described and future research areas highlighted.
PMID- 24357919
TI - Parenthood, child-rearing and fertility in England, 1850-1914.
AB - Fertility declines across Europe and the Anglo-world have been explained as the
result of reversals of intergenerational flows of wealth. According to this
theory, the child was transformed from an economically-useful household asset to
an emotionally-valued parental burden. This article is based on a comparative
study of changing understandings of parenthood in three provincial English
localities between 1850 and 1914. It works from the premise that in order to make
sense of reproductive behaviour, it is essential to examine the meanings that men
and women attached to childlessness, child-rearing and parenthood. It is argued
that there was not a universal shift that made children into burdens. New
understandings of the duties of parenthood did develop, but these were founded on
class-, gender- and place-specific interpretations. These encouraged a minority
of fathers and mothers to believe that together they had the capacity to improve
the lives of their sons and daughters in pioneering ways. Given that husbands and
wives had distinct motives for avoiding rearing many children and that the
discussion of reproduction was shrouded in silence, the dissemination and use of
new ideals of family was crucial in enabling birth control to be thought about
respectably within marriage.
PMID- 24357920
TI - Expression of the chemokine decoy receptor D6 mediates dendritic cell function
and promotes corneal allograft rejection.
AB - PURPOSE: To identify the role of chemokine receptor 6 (D6) expression by
dendritic cells (DCs) and its role in corneal transplant immunity. METHODS: Flow
cytometry analysis was used to assess the expression level of the D6 chemokine
receptor in different leukocyte populations and DC maturation following
lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from
wild-type (WT) or D6(-/-) mice (C57BL/6 background). Mixed-lymphocyte reactions
and delayed-type hypersensitivity assays were performed with bone marrow-derived
DCs from WT or D6(-/-) mice to evaluate T-cell alloreactivity. Adoptive transfer
experiments with T cells from WT or D6(-/-) hosts with BALB/c corneal allografts
were performed. Graft opacity was assessed over an 8-week period, and graft
survival was plotted using Kaplan-Meier survival curves. RESULTS: Expression of
the D6 chemokine receptor was significantly higher in DCs compared to other
leukocyte subpopulations, including neutrophils, lymphocytes, and
monocytes/macrophages. LPS challenge of D6(-/-) bone marrow-derived DCs elicited
significantly lower levels of major histocompatibility complex II and
costimulatory molecules (CD40, CD80, and CD86) compared to WT bone marrow-derived
DCs, indicating the role of the D6 chemokine receptor in DC maturation. Further,
DCs isolated from D6(-/-) mice induced less T-cell proliferation (p<=0.001) and
interferon-gamma production in T cells of draining lymph nodes compared to WT
mice following corneal transplantation (p<=0.001). Moreover, adoptively
transferred T cells from D6(-/-) corneal transplanted mice to WT mice led to
impaired graft rejection, compared to the hosts that received T cells from the WT
transplanted mice. CONCLUSIONS: We demonstrated D6 chemokine receptor expression
by DCs and identified its critical function in multiple aspects of DC biology,
including maturation and consequent elicitation of alloreactive T-cell responses
that are responsible for corneal allograft rejection.
PMID- 24357921
TI - Comparison between axonal and retinal ganglion cell gene expression in various
optic nerve injuries including glaucoma.
AB - PURPOSE: The pathogenesis of retinal ganglion cell loss in glaucoma remains
incompletely understood. Current evidence suggests that the optic nerve (ON) head
and axons are the main site of injury in glaucoma. This study compares changes in
prosurvival and proapoptotic gene expression in ONs with those in retinas in
three models of ocular injury, specifically ON transection (ONTX), N-methyl-D
aspartate (NMDA) retinal toxicity, and experimental glaucoma. METHODS: Rats
(n=240) were divided into three models (ONTX, NMDA retinal toxicity, and
experimental glaucoma). The experimental model was induced unilaterally and the
contralateral eye served as control. Rats were sacrificed at 4-5 different time
points specific for each model. ONs and retinas were isolated for real-time PCR
investigation of expression of selected genes. Immunohistochemistry localized
changes in inhibitor of apoptosis (IAP)-1 and X-linked IAP (XIAP) proteins in
retinas and ONs. Colocalization was measured using Imaris colocalization software
(three-dimensional analysis). RESULTS: The earliest changes in gene expression
occurred in ONs in the ONTX model and in retinas in the NMDA model, as expected.
However, some gene changes occurred first in ONs, while others occurred first in
retinas in the glaucoma model. The expression patterns of the prosurvival genes
IAP-1 and XIAP differed between retinas and ONs of glaucomatous eyes: Both were
upregulated in the retinas, but XIAP was downregulated in the ONs, while IAP-1
stayed unchanged. Colocalization of IAP-1, XIAP, glial fibrillary acidic protein,
and Thymus cell antigen-1 (Thy-1) suggested that IAP-1 was colocalized mostly
with Thy-1 and XIAP with glial fibrillary acidic protein in the ONs. Members of
the B-cell lymphoma 2 (BCL-2) family were similarly involved in the ONs and
retinas of glaucomatous, transected, and NMDA-injected eyes. The expression of
the prosurvival genes, Bcl-2 and Bcl-xl, decreased significantly in both the ONs
and retinas of injured eyes. The proapoptotic genes, BCL2-associated X protein
(BAX) and Bcl-2-associated death promoter (BAD), were significantly upregulated
in both injured retinas and ONs. CONCLUSIONS: The overexpression of XIAP and IAP
1 genes in the retinas was not associated with similar changes in the ONs of
glaucomatous eyes. The lack of activation of these prosurvival genes in the ONs
may explain the increased vulnerability of ONs to elevated intraocular pressure.
PMID- 24357922
TI - Regeneration of the corneal epithelium with conjunctival epithelial equivalents
generated in serum- and feeder-cell-free media.
AB - PURPOSE: An alternative autologous tissue for ocular surface reconstruction is a
potential treatment for the patients with bilateral limbal stem cell deficiency.
For the purpose of regenerative procedures in patients, it is desirable to
eliminate the involvement of xenogeneic components, such as nonhuman sera and
feeder cells. In the present study, we examined the behavior and phenotypic
features of cultured conjunctival epithelial sheets generated in serum- and 3T3
free culture conditions when transplanted into the de-epithelialized limbal
corneal surface. METHODS: Epithelial cells from normal conjunctiva obtained by
neutral protease digestion were expanded by culture in a serum-free low-calcium
medium and set in an air-liquid interface culture for 14 days. The resulting
multilayered epithelial sheets were grafted onto rabbit ocular surfaces made
epithelial-free by alkali treatment. Pre-grafted and post-grafted epithelia were
analyzed by electron microscopy and immunohistochemistry. RESULTS: At graft time
the cultured epithelial sheet consisted of 6-8 layers of properly stratified
epithelium that displayed a CK19(+)/MUC5AC(+)/ CK3 (-)/CK12(-) phenotype,
consistent with the conjunctival epithelial lineage. Two weeks after xeno
grafting the in vivo epithelium consisted of 5-6 well compacted layers expressing
the precursor cell-related protein p63, the proliferation marker Ki67,
desmosomes, hemidesmosomes and its integrin (beta4), and the corneal specific
cytokeratins CK3, and CK12. Conjunctival goblet cell mucin (MUC5AC) was not
visible. The engrafted epithelium stained positively for the anti-human nuclei
antibody, confirming that the epithelial cells on the rabbit corneas were of
human origin. CONCLUSIONS: Our results suggest that conjunctival epithelial
sheets generated in serum- and 3T3-free culture conditions can acquire the
corneal epithelial phenotype when transferred to the in vivo corneal stromal
environment.
PMID- 24357923
TI - Putative free radical-scavenging activity of an extract of Cineraria maritima in
preventing selenite-induced cataractogenesis in Wistar rat pups.
AB - PURPOSE: To investigate the possible free radical-scavenging activity of an
extract of Cineraria maritima on selenite-induced cataractous lenses in Wistar
rat pups. METHODS: In the present study, Wistar rat pups were divided into three
experimental groups. On P10, Group I (control) rat pups received an
intraperitoneal injection of 0.89% saline. Rats in groups II (selenite
challenged, untreated) and III (selenite-challenged, C. maritima treated)
received a subcutaneous injection of sodium selenite (19 MUmol/kg bodyweight);
Group III rat pups also received an intraperitoneal injection of the extract of
C. maritima (350 mg/kg bodyweight) once daily P9-14. Both eyes of each pup were
examined from P16 until P30. Cytochemical localization of nitroblue tetrazolium
salts and generation of superoxide, hydroxyl, and nitric oxide levels were
measured. The expression of the inducible nitric oxide synthase gene was
evaluated with reverse transcription-PCR. Immunoblot analysis was also performed
to confirm the differential expression of the inducible nitric oxide synthase
protein. RESULTS: Subcutaneous injection of sodium selenite led to severe
oxidative damage in the lenticular tissues, shown by increased formation of
formazan crystals, elevated generation of superoxide, hydroxyl, and nitric oxide
radicals, and elevated inducible nitric oxide synthase gene and protein
expression that possibly contributed to the opacification of the lens and thus
cataract formation. When rat pups were treated with intraperitoneal
administration of the extract of C. maritima, the generation of free radicals as
well as the messenger ribonucleic acid and protein expression of inducible nitric
oxide synthase were maintained at near normal levels. CONCLUSIONS: The data
generated by this study suggest that an ethanolic extract of C. maritima possibly
prevents cataractogenesis in a rat model by minimizing free radical generation.
PMID- 24357924
TI - Contractile markers distinguish structures of the mouse aqueous drainage tract.
AB - PURPOSE: Structures of the aqueous humor drainage tract are contractile, although
the tract is not entirely composed of muscle. We characterized the mouse aqueous
drainage tract by immunolabeling contractile markers and determined whether
profiling these markers within the tract distinguished its key structures of the
trabecular meshwork (TM) and ciliary muscle (CM). METHODS: Enucleated eyes from
pigmented C57BL/6 (n=8 mice) and albino BALB/c (n=6 mice) mice were processed for
cryo- and formalin-fixed paraffin-embedded sectioning. Immunofluorescence
labeling was performed for the following: (a) filamentous actin (using
fluorescence-conjugated phalloidin), representing a global contractile marker;
(b) alpha-smooth muscle actin (alpha-SMA), caldesmon, and calponin, representing
classic smooth muscle epitopes; and (c) nonmuscle myosin heavy chain,
representing a nonmuscle contractile protein. Tissue labeling was identified by
confocal microscopy and analyzed quantitatively. Hematoxylin and eosin staining
provided structural orientation. RESULTS: A small portion of the TM faced the
anterior chamber; the rest extended posteriorly alongside Schlemm's canal (SC)
within the inner sclera. Within the drainage tract, filamentous actin labeling
was positive in TM and CM. alpha-SMA and caldesmon labeling was seen primarily
along the CM, which extended from the anterior chamber angle to its posterior
termination beyond the SC near the retina. Low intensity, patchy alpha-SMA and
caldesmon labeling was seen in the TM. Myosin heavy chain immunoreactivity was
primarily found in the TM and calponin was primarily observed in the CM. C57BL/6
and BALB/c comparison showed that pigment obscured fluorescence in the ciliary
body. CONCLUSIONS: Our strategy of profiling contractile markers distinguished
mouse aqueous drainage tract structures that were otherwise indistinguishable by
hematoxylin and eosin staining. The mouse TM was seen as an intervening structure
between SC, a part of the conventional drainage tract, and CM, a part of the
unconventional drainage tract. Our findings provide important insights into the
structural and functional organization of the mouse aqueous drainage tract and a
basis for exploring the role of contractility in modulating aqueous outflow.
PMID- 24357925
TI - Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with
branded and generic prednisolone acetate ophthalmic suspension (1%).
AB - INTRODUCTION: Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax(r)) is a
new polycarbophil-based, nonsettling topical ophthalmic formulation. The
formulation is a semisolid gel at rest and a shear thinning fluid when expressed
through a dropper tip. The present study was undertaken to determine how the
nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone
acetate ophthalmic suspension 1% (Pred Forte(r)) and a generic prednisolone
acetate suspension 1% were used as comparators. METHODS: Drug concentrations of
LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were
determined following simulated dosing - consisting of 2 drops, expressed four
times daily for 2 weeks, with bottles that were shaken or not shaken immediately
prior to expressing the drops. Drug concentrations were determined using a
reverse-phase high-performance liquid chromatography (HPLC) method and reported
as a percentage of the declared (labeled) concentration. Comparative kinetics of
drug particle sedimentation were also determined for each formulation, using
dispersion analysis under gravity. RESULTS: Mean drug concentrations in drops of
all three formulations were within a few percentage points of the declared
concentration when the bottles were shaken for 5 seconds prior to dispensing.
Only LE ophthalmic gel showed consistent and on-target concentrations when the
bottles were unshaken prior to dispensing, with a mean (standard deviation [SD])
percent declared concentration of 102% (1.92%) over the 2-week dosing regimen.
Drug concentrations for the branded and generic prednisolone acetate suspensions
following expression from unshaken bottles were highly variable (overall relative
SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling
significantly below the declared concentration for drops expressed at the
beginning of the 2-week dosing regimen and significantly above the declared
concentration for drops expressed near the end of the dosing regimen. Dispersion
analysis at 120* g showed no drug particle sedimentation for LE ophthalmic gel
over the 24-hour testing period, whereas the prednisolone acetate suspensions
settled in less than 6 hours. CONCLUSION: LE ophthalmic gel 0.5% provided
consistent dose uniformity at the declared concentration whether or not the
bottle was shaken prior to dispensing, whereas Pred Forte(r) and the generic
prednisolone acetate required shaking to provide consistent drug concentrations.
LE ophthalmic gel may be beneficial to patients because it eliminates the
potential impact on the clinical response of both under- and overdosing.
PMID- 24357926
TI - The Influence of Web- Versus Paper-based Formats on the Assessment of Tobacco
Dependence: Evaluating the Measurement Invariance of the Dimensions of Tobacco
Dependence Scale.
AB - The purpose of this study was to examine the influence of mode of administration
(internet-based, web survey format versus pencil-and-paper format) on responses
to the Dimensions of Tobacco Dependence Scale (DTDS). Responses from 1,484
adolescents that reported using tobacco (mean age 16 years) were examined; 354
(23.9%) participants completed a web-based version and 1,130 (76.1%) completed a
paper-based version of the survey. Both surveys were completed in supervised
classroom environments. Use of the web-based format was associated with
significantly shorter completion times and a small but statistically significant
increase in the number of missing responses. Tests of measurement invariance
indicated that using a web-based mode of administration did not influence the
psychometric functioning of the DTDS. There were no significant differences
between the web- and paper-based groups' ratings of the survey's length, their
question comprehension, and their response accuracy. Overall, the results of the
study support the equivalence of scores obtained from web- and paper-based
versions of the DTDS in secondary school settings.
PMID- 24357927
TI - At-risk drinking among diabetic patients.
AB - Diabetes Mellitus is a serious chronic disease, affecting an increasing number of
individuals worldwide. Adherence to diabetes self-care behaviors is key to the
successful management of the disease. At-risk drinking is common among diabetic
patients and is associated with inferior diabetes treatment adherence and
outcomes, resulting in increased mortality and morbidity. Furthermore,
individuals with diabetes who engage in at-risk drinking are also in danger of
incurring the negative consequences of at-risk drinking found in the general
population. Research suggests that alcohol use screening and intervention do not
commonly occur during the course of primary care treatment for diabetes. While
methods for reducing alcohol use in this population have been largely unexplored
to date, brief interventions to reduce at-risk drinking have been well-validated
in other patient populations and offer the promise to reduce at-risk drinking
among diabetic patients, resulting in improved diabetes treatment adherence and
outcomes.
PMID- 24357929
TI - Prescription opioid usage and abuse relationships: an evaluation of state
prescription drug monitoring program efficacy.
AB - CONTEXT: The dramatic rise in the use of prescription opioids to treat non-cancer
pain has been paralleled by increasing prescription opioid abuse. However,
detailed analyses of these trends and programs to address them are lacking.
OBJECTIVE: To study the association between state shipments of prescription
opioids for medical use and prescription opioid abuse admissions and to assess
the effects of state prescription drug monitoring programs (PDMPs) on
prescription opioid abuse admissions. DESIGN AND SETTING: A RETROSPECTIVE
ECOLOGICAL COHORT STUDY COMPARING STATE PRESCRIPTION OPIOID SHIPMENTS (SOURCE:
Automation of Reports and Consolidated Orders Systems database) and inpatient
admissions for prescription opioid abuse (source: Treatment Episode Data Set) in
14 states with PDMPs (intervention group) and 36 states without PDMPs (control
group) for the period 1997-2003. RESULTS: From 1997 to 2003, oxycodone, morphine,
and hydrocodone shipments increased by 479%, 100%, and 148% respectively.
Increasing prescription oxycodone shipments were significantly associated with
increasing prescription opioid admission rates (p < 0.001). PDMP states had
significantly lower oxycodone shipments than the control group. PDMP states had
less increase in prescription opioid admissions per year (p = 0.063). A patient
admitted to an inpatient drug abuse rehabilitation program in a PDMP state was
less likely to be admitted for prescription opioid drug abuse (Odds ratio =
0.775, 95% Confidence Interval 0.764-0.785). CONCLUSIONS: PDMPs appear to
decrease the quantity of oxycodone shipments and the prescription opioid
admission rate for states with these programs. Overall, opioid shipments rose
significantly in PDMP states during the study period indicating a negligible
"chilling effect" on physician prescribing.
PMID- 24357928
TI - Examining the interface between substance misuse and intimate partner violence.
AB - There is considerable theoretical and empirical support for a link between
substance misuse and perpetration and victimization of intimate partner violence.
This review briefly summarizes this literature and highlights current research
that addresses the interface between treatment for substance abuse and intimate
partner violence. Suggestions for future research and clinical implications are
provided.
PMID- 24357930
TI - Who is Ready to Change Illicit Drug Use Behavior: An Emergency Department Study.
AB - OBJECTIVE: To identify emergency department patients who are ready to change
their illicit drug use behavior. METHODS: A cross-sectional study of 198
Emergency Department patients at least 18 years old, seeking emergency department
services, using at least one illicit drug, and scoring positive for alcohol
problem based on CAGE score >= 1. RESULTS: Of the patients, 46% were "not ready"
to change their drug behavior, 21% and 33% were "unsure" and "ready",
respectively. Our results identified that "Readiness to change alcohol behavior"
[t (197) = 3.37, p <= 0.001], health insurance [t (197) = -3.011, p <= 0.003],
number of drug use [t (197) = 2.88, p <= 0.004], and drug-related injury [t (197)
= 1.98, p <= 0.049] were related to readiness to change illicit drug behavior.
CONCLUSION: Our results re-iterate the need for intervention programs that focus
on screening and treatment for both drugs and alcohol.
PMID- 24357932
TI - Principles of MMT.
PMID- 24357931
TI - Impact of one-year methadone maintenance treatment in heroin users in jiangsu
province, china.
AB - CONTEXT: Although the effectiveness of methadone maintenance treatment (MMT) is
well-established in many countries, it is a relatively new therapy for heroin
users in China. Jiangsu Province, a relatively wealthy province, set up 4 MMT
clinics in February 2006. No previous studies have evaluated the impact of MMT in
a wealthy Chinese province. OBJECTIVE: The aim of this study is to evaluate the
impact of a 1-year MMT among heroin users in Jiangsu Province. We investigated
the impact of the treatment by examining the following outcomes: 1) reduction of
heroin use, 2) increase of appropriate sexual intercourse, 3) reduction of
antisocial behavior, 4) increase of better social and family relationships, and
5) HIV prevalence among heroin users in MMT clinics. DESIGN AND SETTING: Repeated
cross-sectional surveys were conducted before and after heroin users in Jiangsu
Province received at least 1-year of treatment in the MMT clinics. A
questionnaire survey was implemented for those who agreed to participate from
March to April 2006, before the initiation of MMT (N = 554). The second survey
was from August to September 2007 and was administered to those who received MMT
for more than 1 year (N = 804). One hundred and ninety-six patients who were
investigated in both surveys were included in a longitudinal study to evaluate
the factors attributable to behavior change. RESULTS: MMT helped in reducing the
percentage of heroin injection and also improved social and familial
relationships. Antisocial behavior, including theft, prostitution, and dealing in
heroin, decreased after 1-year treatment in the MMT clinics. However, the
percentage of patients using condoms was not statistically significant. No case
was found to be HIV-positive among those who received more than 1 year MMT. In
the longitudinal study of 196 patients who participated in both surveys, no
specific demographic variables were found to be associated with heroin use, anti
social behaviors after 1-year MMT. CONCLUSIONS: MMT was thought to reduce heroin
use, antisocial behaviors and HIV prevalence, and increased appropriate sexual
intercourse behaviors and better social and family relationships among heroin
users in a wealthy province in China, which was true regardless of gender, age,
marital status, or working status.
PMID- 24357934
TI - Psychiatric consultation and substance use disorders.
AB - BACKGROUND: A substantial number of patients in general hospitals will evince
substance abuse problems but a majority is unlikely to be adequately identified
in the referral-consultation process. This failure may preclude patients from
receiving effective interventions for substance use disorders. OBJECTIVES: 1. To
evaluate all referred patients for possible substance use disorders. 2. To
ascertain the degree of convergence between patients referred for chemical
problems and the corresponding DSM diagnosis. 3. To compare demographic data for
substance abusing patients and referrals not so classified. 4. To evaluate
conditions concomitant with substance use disorders. METHOD: Consecutive one-year
referrals (524) to consultation-liaison psychiatric services were scrutinized for
chemically-related problems by psychiatric consultants. RESULTS: Of the
referrals, 176 met criteria for substance use disorders (SUD) (57% alcohol; 25%
other drugs; 18% both alcohol and other drugs). Persons diagnosed with SUD tended
to be younger, male, non-Caucasian, unmarried, and unemployed. They were more
likely to be depressed, have liver and other gastrointestinal problems, and to
have experienced traumatic events; they also tended to have current financial
difficulties. Most were referred for SUD evaluation by personnel in general
medicine and family practice. Following psychiatric consultation, SUD designated
patients were referred mainly to substance abuse treatment programs. The only
variable related to recommended inpatient versus outpatient services for
individuals with SUD was the Global Assessment of Functioning Axis (GAF) with
persons having lower estimated functioning more likely to be referred for
inpatient interventions. CONCLUSIONS: These data are similar to the results of
past studies in this area. Unlike previous investigations in the domain of
consultative-liaison psychiatry, financial stressors and specific consultant
recommendations were included in data gathering. Although the results are
encouraging in that individuals with SUD were identified and potentially sent for
appropriate treatment, the likelihood is that many patients with SUD remain
unrecognized and do not receive necessary consultative and treatment services.
PMID- 24357933
TI - Eating disorder symptoms and alcohol use among adolescents in substance abuse
treatment.
AB - OBJECTIVE: To examine the relationship of eating disorder (ED) symptoms with the
severity of alcohol use among adolescents in treatment for alcohol and other
substance use disorders (AOSUDs). METHOD: A sample consisted of 177 adolescents
who participated in outpatient AOSUD treatment programs in Connecticut. Chi
square tests, one-way ANOVAs and Pearson's correlation coefficients were used to
describe the prevalence and correlates of any eating disorders, and the related
symptoms. Multivariate regression was used to test the associations between ED
symptoms and alcohol consumption. RESULTS: 26.4% of the participants had at least
one ED symptom, with the highest number of symptoms occurring in females. The
number of ED symptoms was associated with increases in the number of times that
they became intoxicated in the year before entering treatment, the number of
alcohol-related social problems, and the number of alcohol-related physical
symptoms after taking into consideration the effects of age and gender.
CONCLUSIONS: The prevalence of symptoms of EDs is high in adolescents with
AOSUDs, with the number of ED symptoms correlating with increased alcohol
consumption. Further studies on the course and treatment of adolescents with
AOSUDs and symptoms of EDs are warranted.
PMID- 24357935
TI - Study of arachidonic Acid pathway in human bladder tumor.
AB - Recent epidemiological studies and animal experiments have demonstrated that
nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colorectal
carcinoma. Cyclooxygenase (COX) is the principal target of NSAIDs. COX is the
first oxidase in the process of prostaglandin production from arachidonic acid.
COX enzyme may be involved in the initiation and/or the promotion of
tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX) is also an
initial enzyme in the pathway for producing leukotrienes from arachidonic acid.
Similar to COX, LOX enzyme may also be involved in the initiation and/or
promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR)
gamma is a ligand-activated transcriptional factor belonging to the steroid
receptor superfamily. PPAR-gamma plays a role in both adipocyte differentiation
and tumorigenesis. PPAR-gamma is one target for cell growth modulation of NSAIDs.
In this review, we report the expression of COX-2, LOX and PPAR-gamma in human
bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR
gamma ligand.
PMID- 24357936
TI - Inhibition of the early asthmatic response to inhaled allergen by the 5
lipoxygenase activating protein inhibitor GSK2190915: a dose-response study.
AB - BACKGROUND: GSK2190915, a 5-lipoxygenase activating protein inhibitor, inhibits
the production of cysteinyl leukotrienes and leukotriene B4 and 5-oxo-6,8,11,14
eicosatetraenoic acid. We have previously reported that GSK2190915 100 mg daily
inhibits early and late asthmatic responses to inhaled allergen; the effects of
lower doses have not been reported. This study assessed the dose-response effects
of GSK2190915 10 mg and 50 mg on the early asthmatic response (EAR) to inhaled
allergen. METHODS: Nineteen subjects with mild asthma and an EAR were enrolled in
a randomized, double-blind, three-way crossover study of GSK2190915 10 mg, 50 mg,
and placebo orally once-daily for 3 days. Allergen challenge was performed 2
hours after the third dose. RESULTS: Compared with placebo, GSK2190915 10 mg and
50 mg caused significant, dose-dependent attenuation of the minimum forced
expiratory volume at 1 second (FEV1) absolute change from baseline; mean
treatment differences were 0.21 L (95% confidence interval [CI] 0.04 L, 0.38 L)
and 0.41 L (95% CI 0.24 L, 0.58 L), respectively. GSK2190915 50 mg was more
effective than 10 mg; mean difference between treatments was 0.20 L, (95% CI 0.03
L, 0.36 L). Compared with placebo, GSK2190915 50 mg, but not 10 mg, significantly
inhibited the weighted mean FEV1 absolute change from baseline. CONCLUSION:
GSK2190915 50 mg attenuated the EAR similarly to GSK2190915 100 mg in our
previous study, suggesting 50 mg is at the top of the dose-response curve.
GSK2190915 10 mg is a suboptimal dose. The EAR can be used to assess the
therapeutic dose of a new treatment for asthma.
PMID- 24357938
TI - The Application of an Exploratory Factor Analysis to Investigate the Inter
Relationships amongst Joint Movement During Performance of a Football Skill.
AB - Many studies have investigated the kinematics of sports skills with the majority
describing the kinematics of the technique or investigating significant kinematic
variables that affect performance. Many sports skills are complex three
dimensional movements involving many joints. However, few studies have
investigated the relationships between kinematic variables during performance of
such skills. The aim of this study was to investigate the inter- relationships
among three-dimensional kinematic variables during performance of a lofted instep
soccer kick. A motion analysis system was used to collect kinematic data for 13
skilled amateur soccer players attempting a standardised lofted instep kick.
Three-dimensional angular displacement patterns were reported for the
thoracolumbar spine and right hip joints. Two-dimensional angular displacement
data was reported for the right knee and ankle joints. An exploratory rather than
confirmatory factor analysis was applied, as there is currently no established
theory regarding the kinematics of a lofted instep kick. Factors were extracted
using the Maximum Likelihood Solution and orthogonally rotated using Varimax with
Kaiser normalisation. The inter-relationship among biomechanical variables within
the seven extracted factors was analysed with each factor revealing previously
unknown inter-relationships among variables for different aspects of the kick.
The use of exploratory factor analysis has shown the complex three-dimensional
kinematic inter-relationships for a lofted instep kick. An understanding of these
relationships could prove useful to coaches when instructing, and in the
development of coaching programmes related to the lofted instep kick. Key
PointsMotion analysis of lofted instep kick.Inter-relationship among
biomechanical variables within 7 factors analysed.Each factor revealed previously
unknown inter-relationships among variables for different aspects of the
kick.understanding these relationships could prove useful to coaches in the
development of the lofted instep kick.
PMID- 24357937
TI - The use of metformin is associated with decreased lumbar radiculopathy pain.
AB - Lumbar radiculopathy pain represents a major public health problem, with few
effective long-term treatments. Preclinical neuropathic and postsurgical pain
studies implicate the kinase adenosine monophosphate activated kinase (AMPK) as a
potential pharmacological target for the treatment of chronic pain conditions.
Metformin, which acts via AMPK, is a safe and clinically available drug used in
the treatment of diabetes. Despite the strong preclinical rationale, the utility
of metformin as a potential pain therapeutic has not yet been studied in humans.
Our objective was to assess whether metformin is associated with decreased lumbar
radiculopathy pain, in a retrospective chart review. We completed a retrospective
chart review of patients who sought care from a university pain specialist for
lumbar radiculopathy between 2008 and 2011. Patients on metformin at the time of
visit to a university pain specialist were compared with patients who were not on
metformin. We compared the pain outcomes in 46 patients on metformin and 94
patients not taking metformin therapy. The major finding was that metformin use
was associated with a decrease in the mean of "pain now," by -1.85 (confidence
interval: -3.6 to -0.08) on a 0-10 visual analog scale, using a matched
propensity scoring analysis and confirmed using a Bayesian analysis, with a
significant mean decrease of -1.36 (credible interval: -2.6 to -0.03).
Additionally, patients on metformin showed a non-statistically significant trend
toward decreased pain on a variety of other pain descriptors. Our proof-of
concept findings suggest that metformin use is associated with a decrease in
lumbar radiculopathy pain, providing a rational for larger retrospective trials
in different pain populations and for prospective trials, to test the
effectiveness of metformin in reducing neuropathic pain.
PMID- 24357939
TI - Artificial intelligence in sports biomechanics: new dawn or false hope?
AB - This article reviews developments in the use of Artificial Intelligence (AI) in
sports biomechanics over the last decade. It outlines possible uses of Expert
Systems as diagnostic tools for evaluating faults in sports movements
('techniques') and presents some example knowledge rules for such an expert
system. It then compares the analysis of sports techniques, in which Expert
Systems have found little place to date, with gait analysis, in which they are
routinely used. Consideration is then given to the use of Artificial Neural
Networks (ANNs) in sports biomechanics, focusing on Kohonen self-organizing maps,
which have been the most widely used in technique analysis, and multi-layer
networks, which have been far more widely used in biomechanics in general.
Examples of the use of ANNs in sports biomechanics are presented for javelin and
discus throwing, shot putting and football kicking. I also present an example of
the use of Evolutionary Computation in movement optimization in the soccer throw
in, which predicted an optimal technique close to that in the coaching
literature. After briefly overviewing the use of AI in both sports science and
biomechanics in general, the article concludes with some speculations about
future uses of AI in sports biomechanics. Key PointsExpert Systems remain almost
unused in sports biomechanics, unlike in the similar discipline of gait
analysis.Artificial Neural Networks, particularly Kohonen Maps, have been used,
although their full value remains unclear.Other AI applications, including
Evolutionary Computation, have received little attention.
PMID- 24357940
TI - Predicting the Match Outcome in One Day International Cricket Matches, while the
Game is in Progress.
AB - Millions of dollars are wagered on the outcome of one day international (ODI)
cricket matches, with a large percentage of bets occurring after the game has
commenced. Using match information gathered from all 2200 ODI matches played
prior to January 2005, a range of variables that could independently explain
statistically significant proportions of variation associated with the predicted
run totals and match outcomes were created. Such variables include home ground
advantage, past performances, match experience, performance at the specific
venue, performance against the specific opposition, experience at the specific
venue and current form. Using a multiple linear regression model, prediction
variables were numerically weighted according to statistical significance and
used to predict the match outcome. With the use of the Duckworth-Lewis method to
determine resources remaining, at the end of each completed over, the predicted
run total of the batting team could be updated to provide a more accurate
prediction of the match outcome. By applying this prediction approach to a
holdout sample of matches, the efficiency of the "in the run "wagering market
could be assessed. Preliminary results suggest that the market is prone to
overreact to events occurring throughout the course of the match, thus creating
brief inefficiencies in the wagering market. Key PointsIn excess of 80% of monies
wagered on the outcome of ODI matches are placed after the match has
commenced.Using all past data from ODI matches, multiple linear regression models
are constructed to predict team totals and margin of victory.By combining match
information with prediction models, an 'in the run' prediction process is created
for ODI matches.
PMID- 24357941
TI - Prediction versus reality: the use of mathematical models to predict elite
performance in swimming and athletics at the olympic games.
AB - A number of studies have attempted to predict future Olympic performances in
athletics and swimming based on trends displayed in previous Olympic Games. Some
have utilised linear models to plot and predict change, whereas others have
utilised multiple curve estimation methods based on inverse, sigmoidal,
quadratic, cubic, compound, logistic, growth and exponential functions. The non
linear models displayed closer fits to the actual data and were used to predict
performance changes 10's, 100's and 1000's of years into the future. Some models
predicted that in some events male and female times and distances would crossover
and females would eventually display superior performance to males. Predictions
using mathematical models based on pre-1996 athletics and pre-1998 swimming
performances were evaluated based on how closely they predicted sprints and
jumps, and freestyle swimming performances for both male and females at the 2000
and 2004 Olympic Games. The analyses revealed predictions were closer for the
shorter swimming events where men's 50m and women's 50m and 100m actual times
were almost identical to predicted times. For both men and women, as the swim
distances increased the accuracy of the predictive model decreased, where
predicted times were 4.5-7% faster than actual times achieved. The real trends in
some events currently displaying performance declines were not foreseen by the
mathematical models, which predicted consistent improvements across all athletic
and swimming events selected for in this study. Key PointsPrediction of future
Olympic performance based on previous performance trends.Application of non
linear mathematical equations resulting in better fitting models.Application of
mathematical predictive models to the Olympic sports of athletics and
swimming.Accuracy of mathematical models in predicting sprint events in running
and swimming.A research approach to predict future Olympic performance and set
future performance standards that could be applied to other sports.
PMID- 24357942
TI - Impress your friends and predict the final score: an analysis of the psychic
ability of four target resetting methods used in one-day international cricket.
AB - One-Day cricket's eternal problem is how to fairly account for an interruption
that occurs during a team's innings. Several methods have been applied in the
past, some more successfully than others. Numerous articles have been written
about different target resetting methods applicable in one-day international
cricket and how they "favour "one team over another. In this paper we use an
alternative approach looking at the psychic ability of four target resetting
methods and compare how well they predict the final score based on the present
state of the first innings. We attempt to convert each of methods we investigate
into a ball-by-ball predictive tool. We introduce a terminal interruption to the
first innings at every ball and compute the predicted final score. We ascribe a
nominal value to the difference between the final achieved score and the
prediction given by each method. We compute our own 'Psychic Metric' to enable a
comparison between the four methods. We also develop a computer package to
manipulate the data from matches in which the first innings was completed. Key
PointsPredicting the final score.Creation of a method of comparison.Rain rules
comparisons.
PMID- 24357943
TI - A mathematical modelling approach to one-day cricket batting orders.
AB - While scoring strategies and player performance in cricket have been studied,
there has been little published work about the influence of batting order with
respect to One-Day cricket. We apply a mathematical modelling approach to compute
efficiently the expected performance (runs distribution) of a cricket batting
order in an innings. Among other applications, our method enables one to solve
for the probability of one team beating another or to find the optimal batting
order for a set of 11 players. The influence of defence and bowling ability can
be taken into account in a straightforward manner. In this presentation, we
outline how we develop our Markov Chain approach to studying the progress of runs
for a batting order of non- identical players along the lines of work in baseball
modelling by Bukiet et al., 1997. We describe the issues that arise in applying
such methods to cricket, discuss ideas for addressing these difficulties and note
limitations on modelling batting order for One-Day cricket. By performing our
analysis on a selected subset of the possible batting orders, we apply the model
to quantify the influence of batting order in a game of One Day cricket using
available real-world data for current players. Key PointsBatting order does
effect the expected runs distribution in one-day cricket.One-day cricket has
fewer data points than baseball, thus extreme values have greater effect on
estimated probabilities.Dismissals rare and probabilities very small by
comparison to baseball.Probability distribution for lower order batsmen is
potentially skewed due to increased risk taking.Full enumeration of all possible
line-ups is impractical using a single average computer.
PMID- 24357944
TI - Stochastic Dominance and Analysis of ODI Batting Performance: the Indian Cricket
Team, 1989-2005.
AB - Relative to other team games, the contribution of individual team members to the
overall team performance is more easily quantifiable in cricket. Viewing players
as securities and the team as a portfolio, cricket thus lends itself better to
the use of analytical methods usually employed in the analysis of securities and
portfolios. This paper demonstrates the use of stochastic dominance rules,
normally used in investment management, to analyze the One Day International
(ODI) batting performance of Indian cricketers. The data used span the years 1989
to 2005. In dealing with cricketing data the existence of 'not out' scores poses
a problem while processing the data. In this paper, using a Bayesian approach,
the 'not-out' scores are first replaced with a conditional average. The
conditional average that is used represents an estimate of the score that the
player would have gone on to score, if the 'not out' innings had been completed.
The data thus treated are then used in the stochastic dominance analysis. To use
stochastic dominance rules we need to characterize the 'utility' of a batsman.
The first derivative of the utility function, with respect to runs scored, of an
ODI batsman can safely be assumed to be positive (more runs scored are preferred
to less). However, the second derivative needs not be negative (no diminishing
marginal utility for runs scored). This means that we cannot clearly specify
whether the value attached to an additional run scored is lesser at higher levels
of scores. Because of this, only first-order stochastic dominance is used to
analyze the performance of the players under consideration. While this has its
limitation (specifically, we cannot arrive at a complete utility value for each
batsman), the approach does well in describing player performance. Moreover, the
results have intuitive appeal. Key PointsThe problem of dealing with 'not out'
scores in cricket is tackled using a Bayesian approach.Stochastic dominance rules
are used to characterize the utility of a batsman.Since the marginal utility of
runs scored is not diminishing in nature, only first order stochastic dominance
rules are used.The results, demonstrated using data for the Indian cricket team
are intuitively appealing.The limitation of the approach is that it cannot arrive
at a complete utility value for the batsman.
PMID- 24357945
TI - A probability based approach for the allocation of player draft selections in
Australian rules football.
AB - Australian Rules Football, governed by the Australian Football League (AFL) is
the most popular winter sport played in Australia. Like North American team based
leagues such as the NFL, NBA and NHL, the AFL uses a draft system for rookie
players to join a team's list. The existing method of allocating draft selections
in the AFL is simply based on the reverse order of each team's finishing position
for that season, with teams winning less than or equal to 5 regular season
matches obtaining an additional early round priority draft pick. Much criticism
has been levelled at the existing system since it rewards losing teams and does
not encourage poorly performing teams to win matches once their season is
effectively over. We propose a probability-based system that allocates a score
based on teams that win 'unimportant' matches (akin to Carl Morris' definition of
importance). We base the calculation of 'unimportance' on the likelihood of a
team making the final eight following each round of the season. We then
investigate a variety of approaches based on the 'unimportance' measure to derive
a score for 'unimportant' and unlikely wins. We explore derivatives of this
system, compare past draft picks with those obtained under our system, and
discuss the attractiveness of teams knowing the draft reward for winning each
match in a season. Key PointsDraft choices are allocated using a probabilistic
approach that rewards teams for winning unimportant matches.The method is based
upon Carl Morris' Importance and probabilistic calculations of making the
finals.The importance of a match is calculated probabilistically to arrive at a
DScore.Higher DScores are weighted towards teams winning unimportant matches
which in turn lead to higher draft selections.Provides an alternative to current
draft systems that are based on 'losing to win'.
PMID- 24357946
TI - Statistical Analysis of Notational AFL Data Using Continuous Time Markov Chains.
AB - Animal biologists commonly use continuous time Markov chain models to describe
patterns of animal behaviour. In this paper we consider the use of these models
for describing AFL football. In particular we test the assumptions for continuous
time Markov chain models (CTMCs), with time, distance and speed values associated
with each transition. Using a simple event categorisation it is found that a semi
Markov chain model is appropriate for this data. This validates the use of Markov
Chains for future studies in which the outcomes of AFL matches are simulated. Key
PointsA comparison of four AFL matches suggests similarity in terms of transition
probabilities for events and the mean times, distances and speeds associated with
each transition.The Markov assumption appears to be valid.However, the speed,
time and distance distributions associated with each transition are not
exponential suggesting that semi-Markov model can be used to model and simulate
play.Team identified events and directions associated with transitions are
required to develop the model into a tool for the prediction of match outcomes.
PMID- 24357947
TI - Possession Versus Position: Strategic Evaluation in AFL.
AB - In sports like Australian Rules football and soccer, teams must battle to achieve
possession of the ball in sufficient space to make optimal use of it. Ultimately
the teams need to score, and to do that the ball must be brought into the area in
front of goal - the place where the defence usually concentrates on shutting down
space and opportunity time. Coaches would like to quantify the trade-offs between
contested play in good positions and uncontested play in less promising
positions, in order to inform their decision-making about where to put their
players, and when to gamble on sending the ball to a contest rather than simply
maintain possession. To evaluate football strategies, Champion Data has collected
the on-ground locations of all 350,000 possessions and stoppages in the past two
seasons of AFL (2004, 2005). By following each chain of play through to the next
score, we can now reliably estimate the scoreboard "equity "of possessing the
ball at any location, and measure the effect of having sufficient time to dispose
of it effectively. As expected, winning the ball under physical pressure (through
a "hard ball get") is far more difficult to convert into a score than winning it
via a mark. We also analyse some equity gradients to show how getting the ball 20
metres closer to goal is much more important in certain areas of the ground than
in others. We conclude by looking at the choices faced by players in possession
wanting to maximise their likelihood of success. Key PointsEquity analysis
provides a way of estimating the net value of actions on the sporting
field.Combined with spatial data analysis, the relative merits of gaining
position or maintaining possession can be judged.The advantage of having time and
space to use the ball is measured in terms of scoreboard value, and is found to
vary with field position.Each sport has identifiable areas of the field with high
equity gradients, meaning that it is most important to gain territory there.
PMID- 24357948
TI - Fairer service exchange mechanisms for tennis when some psychological factors
exist.
AB - In a tennis match it is not uncommon for games to 'go with service' (ie. 1-0, 1
1, 2-1, 2-2, 3-2, so on). When this occurs, the player who serves first is either
ahead by one game, or the games' score is equal. Some commentators, players,
argue that the person who serves first has a psychological advantage in that
his/her opponent is very often 'playing catch-up'. Assuming that such a (non
zero) psychological advantage of 'being ahead in the games' score' exists, the
advantage of serving first in a set between two equal players, is determined. In
the presence of such 'front-runner' psychological effects, alternative methods or
rules for allocating service to the players are considered, and some are shown to
be fairer than the present rule. A proposal consisting of two modifications to
the present rules is put forward for consideration. One of these modifications is
very easy to apply. The reverse psychological effect to the above, the 'back-to
the-wall' effect, occurs when a player performs better when behind. The proposal
is seen to be fairer than the present method for the cases in which both players
A has either a positive or negative psychological effect and player B also has an
equivalent positive or negative effect. Further, the application of the proposal
to doubles is also considered and a modification for doubles suggested for
consideration. Key PointsThis study shows that a scoring system that is typically
considered fair, may in fact not be fair when some psychological factors are
added.Assuming a 'front-runner' (and/or a 'back-to-the-wall') effect exists in
tennis for both players, the advantage of serving first in a set between two
equal players, is determined.Given the presence of such psychological factors in
tennis, fairer methods of allocating service to the players both within sets and
across sets are determined.An additional modification for tennis doubles is also
recommended.A method for improving the fairness in the one-day and test versions
of a series of cricket matches is suggested.
PMID- 24357949
TI - Modelling the interaction in game sports - relative phase and moving
correlations.
AB - Model building in game sports should maintain the constitutive feature of this
group of sports, the dynamic interaction process between the two parties. For
single net/wall games relative phase is suggested to describe the positional
interaction between the two players. 30 baseline rallies in tennis were examined
and relative phase was calculated by Hilbert transform from the two time-series
of lateral displacement and trajectory in the court respectively. Results showed
that relative phase indicates some aspects of the tactical interaction in tennis.
At a more abstract level the interaction between two teams in handball was
studied by examining the relationship of the two scoring processes. Each process
can be conceived as a random walk. Moving averages of the scoring probabilities
indicate something like a momentary strength. A moving correlation (length = 20
ball possessions) describes the momentary relationship between the teams'
strength. Evidence was found that this correlation is heavily time-dependent, in
almost every single game among the 40 examined ones we found phases with a
significant positive as well as significant negative relationship. This
underlines the importance of a dynamic view on the interaction in these games.
Key PointsGame sports.Mathematical modelling.Relative phase.Random walks.
PMID- 24357950
TI - An Analysis of Ten Years of the Four Grand Slam Men's Singles Data for Lack of
Independence of Set Outcomes.
AB - The objective of this paper is to use data from the highest level in men's tennis
to assess whether there is any evidence to reject the hypothesis that the two
players in a match have a constant probability of winning each set in the match.
The data consists of all 4883 matches of grand slam men's singles over a 10 year
period from 1995 to 2004. Each match is categorised by its sequence of win (W) or
loss (L) (in set 1, set 2, set 3,...) to the eventual winner. Thus, there are
several categories of matches from WWW to LLWWW. The methodology involves fitting
several probabilistic models to the frequencies of the above ten categories. One
four-set category is observed to occur significantly more often than the other
two. Correspondingly, a couple of the five-set categories occur more frequently
than the others. This pattern is consistent when the data is split into two five
year subsets. The data provides significant statistical evidence that the
probability of winning a set within a match varies from set to set. The data
supports the conclusion that, at the highest level of men's singles tennis, the
better player (not necessarily the winner) lifts his play in certain situations
at least some of the time. Key PointsUsing grand slam men's singles data, the
probability of winning a set has been shown to vary from set to set.The data
provides statistical evidence that the better player (not necessarily the winner)
in some matches is able to lift his play in certain situations. This result gives
encouragement to the better player when in difficulties in a match.The authors
found no evidence that the weaker player was able to lift his play. The weaker
player, when ahead in a match, should be on his guard for his opponent to have a
real capacity to lift his game.
PMID- 24357951
TI - Reducing the likelihood of long tennis matches.
AB - Long matches can cause problems for tournaments. For example, the starting times
of subsequent matches can be substantially delayed causing inconvenience to
players, spectators, officials and television scheduling. They can even be seen
as unfair in the tournament setting when the winner of a very long match, who may
have negative aftereffects from such a match, plays the winner of an average or
shorter length match in the next round. Long matches can also lead to injuries to
the participating players. One factor that can lead to long matches is the use of
the advantage set as the fifth set, as in the Australian Open, the French Open
and Wimbledon. Another factor is long rallies and a greater than average number
of points per game. This tends to occur more frequently on the slower surfaces
such as at the French Open. The mathematical method of generating functions is
used to show that the likelihood of long matches can be substantially reduced by
using the tiebreak game in the fifth set, or more effectively by using a new type
of game, the 50-40 game, throughout the match. Key PointsThe cumulant generating
function has nice properties for calculating the parameters of distributions in a
tennis matchA final tiebreaker set reduces the length of matches as currently
being used in the US OpenA new 50-40 game reduces the length of matches whilst
maintaining comparable probabilities for the better player to win the match.
PMID- 24357952
TI - Low compression tennis balls and skill development.
AB - Coaching aims to improve player performance and coaches have a number of coaching
methods and strategies they use to enhance this process. If new methods and ideas
can be determined to improve player performance they will change coaching
practices and processes. This study investigated the effects of using low
compression balls (LCBs) during coaching sessions with beginning tennis players.
In order to assess the effectiveness of LCBs on skill learning the study employed
a quasi-experimental design supported by qualitative and descriptive data.
Beginner tennis players took part in coaching sessions, one group using the LCBs
while the other group used standard tennis balls. Both groups were administered a
skills at the beginning of a series of coaching sessions and again at the end. A
statistical investigation of the difference between pre and post-test results was
carried out to determine the effect of LCBs on skill learning. Additional
qualitative data was obtained through interviews, video capture and the use of
performance analysis of typical coaching sessions for each group. The skill test
results indicated no difference in skill learning when comparing beginners using
the LCBs to those using the standard balls. Coaches reported that the LCBs
appeared to have a positive effect on technique development, including aspects of
technique that are related to improving power of the shot. Additional benefits
were that rallies went on longer and more opportunity for positive reinforcement.
In order to provide a more conclusive answer to the effects of LCBs on skill
learning and technique development recommendations for future research were
established including a more controlled experimental environment and larger
sample sizes across a longer period of time. Key PointsLCB may aid skill learning
in tennis.Qualitative indicators.Statistical evidence not conclusive.Further
studies of larger groups recommended.
PMID- 24357953
TI - 'Resting toucher': a time and motion analysis of elite lawn bowls.
AB - Whilst numerous investigations have explored the physical demands placed upon
competitive sportspeople from a wide array of sports little is known about the
physical demands placed on lawn bowlers. The purpose of this study was to
ascertain the movement activities of Australian representative singles and pairs
players and to determine the frequency and duration of these activities. One
match each of two male and two female players (one singles and one pairs player
per gender) were videotaped during an international tournament. During playback
of the videotaped matches (n = 4), a single observer coded the players'
activities into five distinct categories (waiting, walking forward, walking
backward, jogging and bowling) using a computerised video editing system
(GamebreakerTM Digital Video Analysis System). Field calibration of players over
30m for forward motions and 15m for the backward motion was performed to allow
for the estimation of total distance covered during the match. Heart rate was
monitored during each match. The duration of a match was found to be (mean +/-
SD) 1hr 28 +/- 15mins. The total distance covered during each match was 2093 +/-
276m. The mean percentage of match time spent in each motion was: waiting, 61.8
+/- 9.3%; walking forward, 22.3 +/- 5.6%; walking backward, 2.0 +/- 0.4%;
jogging, 1.1 +/- 0.5%; and bowling, 8.5 +/- 4.2%. Average heart rate was found to
be 57 +/- 7% of age-predicted HRmax with a maximum of 78 +/- 9% of age-predicted
HRmax. The results of this study suggest that playing lawn bowls at an
international level requires light-moderate intensity activity similar to that
reported for golf. Key PointsThe duration of a lawn bowls match played in sets
play was 1hr 28 +/- 15mins.The majority (65%) of this time was spent in the
motion category "waiting".Players covered more than 2000m during a match with the
vast majority (85%) in the form of forward walking.The average heart rate was 107
+/- 15 bpm or 57 +/- 7% of age-predicted HRmax.The game of lawn bowls requires
light-moderate intensity activity and appears to be similar to the physical
demands of golf.
PMID- 24357954
TI - Maximizing height, distance or rotation from real-time analysis visualisation of
take-off angles and speed.
AB - Studies to optimise take off angles for height or distance have usually involved
either a time-consuming invasive approach of placing markers on the body in a
laboratory setting or using even less efficient manual frame-by-frame joint angle
calculations with one of the many sport science video analysis software tools
available. This research introduces a computer-vision based, marker-free, real
time biomechanical analysis approach to optimise take-off angles based on speed,
base of support and dynamically calculated joint angles and mass of body
segments. The goal of a jump is usually for height, distance or rotation with
consequent dependencies on speed and phase of joint angles, centre of mass COM)
and base of support. First and second derivatives of joint angles and body part
COMs are derived from a Continuous Human Movement Recognition (CHMR) system for
kinematical and what-if calculations. Motion is automatically segmented using
hierarchical Hidden Markov Models and 3D tracking is further stabilized by
estimating the joint angles for the next frame using a forward smoothing Particle
filter. The results from a study of jumps, leaps and summersaults supporting
regular knowledge of results feedback during training sessions indicate that this
approach is useful for optimising the height, distance or rotation of skills. Key
PointsComputer-vision based marker-free tracking.Real-time biomechanical
analysis.Improve tracking using a forward smoothing Particle filter.Automatically
segment using hierarchical Hidden Markov Models.Recognize skills using segmented
motion.Optimize take-off angles using speed, base of support, joint angles and
mass of body segments.Optimize height, distance or rotation of skills.
PMID- 24357955
TI - Cuboid syndrome: a review of the literature.
AB - The purpose of this review was to inform all medical health care professionals
about cuboid syndrome, which has been described as difficult to recognize and is
commonly misdiagnosed, by explaining the etiology of this syndrome, its clinical
diagnosis in relation to differential diagnoses, commonly administered treatment
techniques, and patient outcomes. A comprehensive review of the relevant
literature was conducted with MEDLINE, EBSCO, and PubMed (1960 - Present) using
the key words cuboid, cuboid syndrome, foot anatomy, tarsal bones, manual
therapy, and manipulation. Medical professionals must be aware that any lateral
foot and ankle pain may be the result of cuboid syndrome. Once properly
diagnosed, cuboid syndrome responds exceptionally well to conservative treatment
involving specific cuboid manipulation techniques. Other methods of conservative
treatment including therapeutic modalities, therapeutic exercises, padding, and
low dye taping techniques are used as adjuncts in the treatment of this syndrome.
Immediately after the manipulation is performed, the patient may note a decrease
or a complete cessation of their symptoms. Occasionally, if the patient has had
symptoms for a longer duration, several manipulations may be warranted throughout
the course of time. Due to the fact radiographic imaging is of little value, the
diagnosis is largely based on the patient's history and a collection of signs and
symptoms associated with the condition. Additionally, an understanding of the
etiology behind this syndrome is essential, aiding the clinician in the diagnosis
and treatment of this syndrome. After the correct diagnosis is made and a proper
treatment regimen is utilized, the prognosis is excellent. Key PointsDefine the
poorly understood condition of cuboid syndrome.Provide an understanding of the
anatomical structures involved.Provide an explanation as to the cause of this
syndrome.Demonstrate ways to evaluate by making a differential diagnosis.To
inform health care professionals about management and treatment of cuboid
syndrome.
PMID- 24357956
TI - Augmentation vs Nonaugmentation Techniques for Open Repairs of Achilles Tendon
Ruptures with Early Functional Treatment: A Prospective Randomized Study.
AB - A prospective randomized study was conducted in order to compare augmentation
technique versus nonaugmentation technique, followed by early functional
postoperative treatment, for operative repair of Achilles tendon ruptures. Twenty
four consecutive patients were assigned to two groups. Group I included 12
patients treated with Lindholm augmentation technique, whereas group II included
12 patients treated with modified Kessler end-to-end repair. Thereafter, these
patients had postoperative management with a below-knee-cast for three weeks. The
physioteraphy was initiated immediately after the cast was removed. Full weight
bearing was allowed after five weeks postoperatively in the both groups. Two
patients had reruptures in group II, whereas group I had prolonged operative time
significantly. The patients with reruptures underwent reoperations and at the
most final follow-up, it was observed that they could not resume to sporting
activities. The other objective and subjective results were similar between two
groups. Because of quite high rerupture rate in the group of patients treated
with nonaugmentation technique, we favor functional postoperative treatment with
early ankle movement in the patients treated with augmentation technique for the
management of acute rupture of the Achilles tendon. Key PointsA prospective
randomized study was conducted in order to compare augmentation technique versus
nonaugmentation technique, followed by early functional postoperative treatment,
for operative repair of Achilles tendon ruptures.Group I included 12 patients
treated with Lindholm augmentation technique, whereas group II included 12
patients treated with modified Kessler end-to-end repair.Functional postoperative
treatment with early ankle movement in the patients treated with augmentation for
the management of acute rupture of the Achilles tendon is recommended.
PMID- 24357957
TI - Perceived barriers to physical activity in university students.
AB - Many studies which were published in other countries identified certain benefits
and barriers to physical activity among young people. But there is no data about
the subject pertaining to Turkish adolescents. This study tries to rectify this
with a study of Turkish university students. Undergraduate university students (n
= 303) were recruited to the study. Current exercise habits and perceived
barriers to physical activity were assessed in the sample. Using a Likert Type
scale, participants responded an instrument with 12 items representing barriers
to physical activity. Mean scores were computed. External barriers were more
important than internal barriers. "Lack of time due to busy lesson schedule", "My
parents give academic success priority over exercise. "and "lack of time due to
responsibilities related to the family and social environment "were most cited
items for physical activity barriers. There is a need for future research, which
will be carried out with larger sample groups to develop national standardized
instrument. It will be helpful for accurately identify perceived barriers and
then recommend changes to enhance physical activity among young people. Key
PointsThe purpose of this study was to analyze perceived barriers to physical
activity in the university students.The results showed that not having enough
time was the most important barrier for not participating in physical activity
among our samples.This study with relatively small sample must be considered as
pilot study for related studies in the future.
PMID- 24357958
TI - Effect of caffeine on oxidative stress during maximum incremental exercise.
AB - Caffeine (1,3,7-trimethylxanthine) is an habitual substance present in a wide
variety of beverages and in chocolate-based foods and it is also used as adjuvant
in some drugs. The antioxidant ability of caffeine has been reported in contrast
with its pro- oxidant effects derived from its action mechanism such as the
systemic release of catecholamines. The aim of this work was to evaluate the
effect of caffeine on exercise oxidative stress, measuring plasma vitamins A, E,
C and malonaldehyde (MDA) as markers of non enzymatic antioxidant status and
lipid peroxidation respectively. Twenty young males participated in a double
blind (caffeine 5mg.kg- 1 body weight or placebo) cycling test until exhaustion.
In the exercise test, where caffeine was ingested prior to the test, exercise
time to exhaustion, maximum heart rate, and oxygen uptake significantly
increased, whereas respiratory exchange ratio (RER) decreased. Vitamins A and E
decreased with exercise and vitamin C and MDA increased after both the caffeine
and placebo tests but, regarding these particular variables, there were no
significant differences between the two test conditions. The results obtained
support the conclusion that this dose of caffeine enhances the ergospirometric
response to cycling and has no effect on lipid peroxidation or on the antioxidant
vitamins A, E and C. Key PointsCaffeine ingestion may improve maximal aerobic
performance in non trained men.Cellular oxidative damage is not altered by
caffeine ingestion in maximal aerobic exercises.Antioxidant response to exercise,
vitamins A, E and C, is not modified by caffeine action in maximal aerobic
efforts.
PMID- 24357959
TI - Effects of palm vitamin e supplementation on exercise-induced oxidative stress
and endurance performance in the heat.
AB - This study investigates the effects of tocotrienol-rich palm vitamin E
supplementation on exercise-induced lipid peroxidation and endurance performance
in the heat. In a double blind, cross-over study, eighteen healthy, male
recreational athletes completed two endurance running trials, until exhaustion,
on a motorized treadmill at 70% VO2max on two separate occasions following a 6
week supplementation regimen of either tocotrienol-rich palm vitamin E (E) or
placebo (P). Both trials were conducted in the heat (31 degrees C, 70% relative
humidity). During the trials, rectal temperature (Trec), ratings of perceived
exertion (RPE) and oxygen uptake (VO2) were recorded. Blood samples were
collected for the determination of plasma volume changes (PVC), malondialdehyde
(MDA), creatine kinase (CK), total antioxidant status (TAS) and vitamin E. After
the supplementation regimen, serum alpha-tocopherol increased ~33% but serum
concentrations of tocotrienols were negligible. No significant differences were
evident in mean Trec, RPE, VO2 or in the time to exhaustion between the E
supplemented and the placebo- supplemented groups. Similarly, mean PVC, CK and
TAS were also not different between the two groups. Resting plasma mean MDA
concentration in the E-supplemented group was significantly lower than that in
the placebo-supplemented group. At exhaustion, plasma mean MDA was higher than
the resting values in both groups. Although tocotrienol-rich palm vitamin E
supplementation decreased lipid peroxidation at rest and, to some extent, during
exercise in the heat, as evident from the lower MDA levels, it however did not
enhance endurance running performance or prevent exercise-induced muscle damage
or influenced body core temperature or plasma volume changes during exercise in
the heat. Key Pointsreduced lipid peroxidation at rest.did not enhance endurance
running performance in the heat.did not prevent exercise-induced muscle damage as
indicated by CK activity.
PMID- 24357960
TI - Oxygen cost during treadmill walking with hip and knee immobilised.
AB - The aim of this study was to determine the effect of immobilising the knee and
hip on the oxygen cost (ml.kg(-1).min(-1)) to velocity relationship during
treadmill walking. The study was a prospective experimental conducted in a
Rehabilitation centre. Ten healthy individuals, five men and five women, with no
gait abnormality participated. Following familiarisation five men and five women
walked on a treadmill and selected their own, free "comfortable walking velocity
"(SSWS). Subjects then performed an incremental test at -60 to +60% of SSWS.
Individuals later repeated the test with the knee and hip of one limb
immobilised. Samples of expired air were measured at each velocity and the oxygen
cost (ml.kg(-1).min(-1)) to Froude number (Fr) relationship plotted (where
calculation of Fr normalizes for subjects of differing leg length and acts as an
index of velocity). There was a higher oxygen cost, and lower Fr at SSWS during
immobilised (0.21 +/- 0.03 ml.kg(-1).min(-1); Fr = 0.12 +/- 0. 03) compared with
free walking (0.16 +/- 0.02 ml.kg(-1).min(-1); Fr = 0.18 +/- 0.04) (p < 0. 01).
Statistical analysis demonstrated that during immobilised walking an inverse fit
(y = beta0 + beta1/x) and for free walking a cubic fit (y = beta0 + beta1x +
beta2x(2) + beta3x(3) ) best fitted the data. Hip and knee immobilisation
increased the oxygen cost at SSWS and altered the oxygen cost to Fr relationship.
The results have implications in selecting optimal walking velocities in
individuals with impairments affecting mobility such as hemiplegic gait. Key
PointsWalking with one limb immobilised requires greater energy cost than normal
free walking.This has clinical implications when developing rehabilitation
strategies for patients who mobility problems such as those with hemi paretic
gait.
PMID- 24357961
TI - The influence of a foot orthotic on lower extremity transverse plane kinematics
in collegiate female athletes with pes planus.
AB - Non-contact anterior cruciate ligament (ACL) injuries in female athletes remain
prevalent. Athletes with excessive foot pronation have been identified to be at
greater risk for non-contact ACL injury. Excessive foot pronation has been linked
to increased medial tibial rotation. Increased medial tibial rotation heightens
ACL strain and has been observed at or near the time of ACL injury. Foot
orthotics have been shown to decrease medial tibial rotation during walking and
running tasks. The effect of a foot orthotic on activities that simulate a non
contact ACL injury mechanism (i.e. landing) however is unknown. Therefore, the
objective of this study was to determine whether a foot orthotic was capable of
altering transverse plane lower extremity kinematics in female athletes during
landing. Twenty uninjured collegiate female athletes participating in the sports
of basketball, soccer or volleyball with pes planus volunteered. Utilizing a
repeated measures counterbalanced design, subjects completed two landing tasks
with and without a foot orthotic using standardized footwear. The prefabricated
orthotic had a rigid shell and a 6 extrinsic rear-foot varus post. Dependent
measures included initial contact angle, peak angle, excursion and time to peak
angle for both the tibia and femur. Statistical analysis suggested that the
selected foot orthosis had little influence over lower extremity transverse plane
kinematics. Several factors including: the limitation of a static measure to
predict dynamic movement, inter-subject variability and the physical
characteristics of the orthotic device likely account for the results. Future
research should examine the influence of different types of foot orthotics not
only on lower extremity kinematics but also tibiofemoral kinetics. Key
PointsLower extremity transverse plane kinematics in female athletes during a
landing task exhibit substantial variability.A rigid prefabricated foot orthotic
does not significantly alter transverse plane lower extremity kinematics in
female athletes with a navicular drop of at least 8mm.Additional study is
necessary before firm conclusions regarding the influence of an orthotic device
on lower extremity kinematics, kinetics, neuromuscular control and ultimately
injury rates can be made.
PMID- 24357962
TI - Quantification of lumbar endurance on a backup lumbar extension dynamometer.
AB - We evaluated the reliability of static and dynamic lumbar muscle endurance
measurements on a BackUP lumbar extension dynamometer. Sixteen healthy
participants (8 male; 8 female) volunteered for this investigation. Fifty percent
of each participant's body weight was calculated to determine the weight load
utilized for the static (holding time) and dynamic (repetitions) lumbar extension
endurance tests. Four separate tests (2 static, 2 dynamic) were conducted with at
least a 24-hour rest period between tests. Test-retest intraclass correlations
were shown to be high (static lumbar endurance, ICC = 0.92 (p < 0.0005); dynamic
lumbar endurance, ICC = 0.93 (p < 0.0005) for both of the performed tests. Our
results demonstrated that static and dynamic lumbar endurance can be assessed
reliably on a BackUP lumbar extension dynamometer. Key PointsReliability studies
that test lumbar endurance on machines that effectively stabilize the pelvis and
isolate the lumbar extensors are limited.This is the first study to report
reliability measures of static and dynamic lumbar endurance on a BackUP lumbar
extension dynamometer.Static and dynamic lumbar endurance on a BackUP lumbar
extension dynamometer, which uses a variety of pelvic stabilization mechanisms,
can be reliably assessed in apparently healthy individuals.Future research is
necessary to examine the reliability of lumbar extension endurance on the BackUP
dynamometer in patient populations and validity in various settings.
PMID- 24357963
TI - Relationship Between %Heart Rate Reserve And %VO2 Reserve During Elliptical
Crosstrainer Exercise.
AB - The primary purpose of the study was to determine the relationships between %HRR
vs. %VO2R and %HRR vs. %VO2max during maximal elliptical crosstrainer (ECT)
exercise. A secondary aim was to compare the %HRR vs. %VO2R and %HRR vs. %VO2max
relationships between maximal ECT and treadmill (TM) exercise. Adult subjects (n
= 48) completed a maximal exercise test on the ECT, with a subgroup (N = 24) also
performing a maximal exercise test on the TM. Continuous HR and VO2 data were
analyzed via linear regression to determine y-intercept and slope values for %HRR
vs. %VO2R and %HRR vs. %VO2max. Student t-tests were used to determine whether
the mean y-intercept and slope values differed from the line of identity (y
intercept = 0, slope = 1). For each group, both the y-intercept and slope for
%HRR vs. %VO2R fit the line of identity. Conversely, for all groups both the y
intercept and slope for %HRR vs. %VO2max were significantly different (p < 0.001)
from the line of identity (y-intercept ? 0, slope ? 1). In comparing the
regressions of %HRR vs. %VO2R between exercise modes, there were no significant
differences (p > 0.05) for either y-intercept (ECT = 0.3 vs. TM = -0.3, p =
0.435) or slope (ECT = 1.01 vs. TM = 1.00, p = 0.079) values. In agreement with
previous research on TM and cycle exercise, it was found that %HRR is more
closely aligned with %VO2R, rather than %VO2max during ECT exercise.
Additionally, it was found that the regressions of %HRR vs. %VO2R and %HRR vs.
%VO2max were equivalent between the ECT and TM. Key PointsThe present study
showed that %HRR is aligned with %VO2R, not %VO2max, during maximal ellipitcal
crosstrainer exercise.It was found that the relationships between %HRR vs. %VO2R
and %HRR vs. %VO2max were equivalent between the ellipitcal crosstrainer and
treadmill.This study revealed that the elliptical crosstrainer produced similar
maximal physiological values (VO2max, HRmax, RERmax) compared to treadmill
running during VO2max testing.
PMID- 24357964
TI - Estradiol in females may negate skeletal muscle myostatin mRNA expression and
serum myostatin propeptide levels after eccentric muscle contractions.
AB - Eccentric contractions produce a significant degree of inflammation and muscle
injury that may increase the expression of myostatin. Due to its anti- oxidant
and anti-flammatory effects, circulating 17-beta estradiol (E2) may attenuate
myostatin expression. Eight males and eight females performed 7 sets of 10 reps
of eccentric contractions of the knee extensors at 150% 1-RM. Each female
performed the eccentric exercise bout on a day that fell within her mid-luteal
phase (d 21-23 of her 28-d cycle). Blood and muscle samples were obtained before
and 6 and 24 h after exercise, while additional blood samples were obtained at 48
and 72 h after exercise. Serum E2 and myostatin LAP/propeptide (LAP/pro) levels
were determined with ELISA, and myostatin mRNA expression determined using RT
PCR. Data were analyzed with two-way ANOVA and bivariate correlations (p < 0.05).
Females had greater levels of serum E2 throughout the 72- h sampling period (p <
0.05). While males had greater body mass and fat-free mass, neither was
correlated to the pre-exercise levels of myostatin mRNA and LAP/pro for either
gender (p > 0.05). Compared to pre-exercise, males had significant increases (p <
0.05) in LAP/propetide and mRNA of 78% and 28%, respectively, at 24 h post
exercise, whereas females underwent respective decreases of 10% and 21%. E2 and
LAP/propeptide were correlated at 6 h (r = -0.804, p = 0.016) and 24 h post-
exercise (r = -0.841, p = 0.009) in males, whereas in females E2 levels were
correlated to myostatin mRNA at 6 h (r =0.739, p = 0.036) and 24 h (r = 0.813, p
= 0.014) post-exercise and LAP/propeptide at 6 h (r = 0.713, p = 0.047) and 24 h
(r = 0.735, p = 0.038). In females, myostatin mRNA expression and serum
LAP/propeptide levels do not appear to be significantly up-regulated following
eccentric exercise, and may be due to higher levels of circulating E2. Key
PointsThe pre-exercise levels of myostatin mRNA and propeptide were not
significantly different between genders, and even though the total body mass and
fat-free mass of males were significantly greater than females, neither was
correlated to myostatin mRNA or LAP/propeptide.Myostatin mRNA expression in
females is less than in males 24 h after a single bout of eccentric
exercise.Myostatin LAP/propeptide levels in females are lower in females than in
males 24 h after a single bout of eccentric exercise, thereby suggesting a gender
specific mechanism in which females may be less responsive to eccentric exercise
than males.Myostatin mRNA expression in females is attenuated, possibly due to
inhibition in myostatin signaling, and appears to be more related to the presence
of a higher level of circulating E2 rather than body composition.Due to their
higher level of E2, females seem to be less susceptible to the mechanism by which
eccentric exercise apparently up-regulates myostatin mRNA expression in males.
PMID- 24357965
TI - Influence of chronic exercise on red cell antioxidant defense, plasma
malondialdehyde and total antioxidant capacity in hypercholesterolemic rabbits.
AB - Despite the knowledge on the antiatherogenic effects of exercise, the mechanism
by which exercise reduces atherogenic risk remains unknown. In this study, we
investigated the hypothesis that chronic exercise-induced oxidative stress may
increase plasma total antioxidant capacity and antioxidant defense in the red
cells. For 8 weeks, 60 male Dutch rabbits were fed rabbit chow with or without
the addition of 2% cholesterol. The animals were further divided into rest and
exercise groups (n = 15 for each group). Animals in exercise groups ran on a
rodent treadmill at 15 m/min for 10 to 60 minutes gradually for 5 days per week
for a total of 8 weeks. At the end of experiments, blood samples were collected
and glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT)
activities were determined in red blood cells. Total antioxidant capacity (TAC),
malondialdehyde (MDA) and total thiol (T-SH) levels were measured in plasma.
Thoracic aorta and carotid arteries were isolated for histological examination to
evaluate atherosclerosis. Eight weeks of chronic exercise reduced atherogenic
diet-induced atherosclerotic lesions in all the arteries studied, along with
positive changes in cholesterol profile, especially increase of serum HDL-C
level. Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both
control and hypercholesterolemic diet groups. Erythrocyte catalase activity was
significantly increased by chronic exercise (p < 0.05), whereas total SOD
activity rose with exercise only in the control group. Surprisingly, GPX activity
was significantly reduced (P < 0.05) in response to exercise in the control group
and also in the high cholesterol diet group. Exercise is a useful tool for the
prevention and regression of atherosclerosis which is evident by our findings of
the enhancement of plasma TAC and positive change in serum cholesterol profile.
However, the effect of exercise on red cell antioxidant activities is limited in
the hypercholesterolemic animals compared to control animals, possibly in part
because of alterations in the ability to adapt to exercise-induced oxidative
stress in high cholesterol diet. Key PointsPlasma MDA, TAC and T-SH
concentrations were enhanced by exercise in both control and high cholesterol
diet groups.GPX activity was significantly reduced in response to exercise in the
control group and also in the high cholesterol diet group.Eight weeks of chronic
exercise reduced atherogenic diet-induced atherosclerotic lesions in all the
arteries studied.
PMID- 24357966
TI - Indirect calorimetry during ultradistance running: a case report.
AB - The purpose was to determine the energy expenditure during ultradistance trail
running. A portable metabolic unit was carried by a male subject for the first
64.5 km portion of the Western States 100 running race. Calibrations were done
with known gases and volumes at ambient temperature, humidity and pressure (23
40.5 degrees C and 16-40% respectively). Altitude averaged 1692.8 +/- 210 m
during data collection. The male subject (36 yrs, 75 kg, VO2max of 67.0 ml.kg(
1).min(-1)) had an average (mean +/- SD) heart rate of 132 +/- 9 bpm, oxygen
consumption of 34.0 +/- 6.8 ml.kg(-1).min(-1), RER of 0.91 +/- 0.04, and VE of
86.0 +/- 14.3 L.min(-1) during the 21.7 km measuring period. This represented an
average of 51% VO2max and 75% heart rate maximum. Energy expenditure was 12.6 +/-
2.5 kcals.min(-1), or 82.7 +/- 16.6 kcals.km(-1) (134 +/- 27 kcals.mile(-1)) at
68.3 +/- 12.5% carbohydrate. Extrapolation of this data would result in an energy
expenditure of >13,000 kcals for the 160 km race, and an exogenous carbohydrate
requirement of >250 kcal.hr(-1). The energy cost of running for this subject on
separate, noncompetitive occasions ranged from 64.9 +/- 8.5 to 74.4 +/- 5.5
kcals.km(-1) (105 +/- 14 to 120 +/- 9 kcals.mile(-1)). Ultradistance trail
running increases energy expenditure above that of running on nonundulating
terrain, which may result in underestimating energy requirements during these
events and subsequent undernourishment and suboptimal performance. Key PointsThe
energy cost of running is elevated during ultradistance trail races compared to
normal running conditions.This elevated energy cost results in a ~12% increase in
energy expenditure for a given distance.Ad libitum energy intake may grossly
underestimate the demand of ultradistance running in the conditions investigated
in this paper, thus jeopardizing race performance.
PMID- 24357967
TI - The Effect of Body Build and BMI on Aerobic Test Performance in School Children
(10-15 Years).
AB - Body Mass Index (BMI) has often questionably been used to define body build. In
the present study body build was defined more specifically using fat free mass
index (FFMI = fat free mass normalised to the stature) and fat mass index (FMI =
fat mass normalised to stature). The body build of an individual is 'solid' in
individuals with a high FFMI for their FMI and is 'slender' in individuals with a
low FFMI relative to their FMI. The aim of the present study was to investigate
the association between aerobic test performance and body build defined as solid,
average or slender in 10 to 15 year old children. Five-hundred-and-two children
(53% boys) aged 10 to 15 years of age were included in the study. Aerobic test
performance was estimated with an incremental cycle ergometer protocol and a
shuttle run test. BMI and percentage fat (by skin folds) were determined to
calculate FMI and FFMI. After adjustment for differences in age, gender and body
mass the solid group achieved a significantly higher maximal power output (W) and
power output relative to body mass (W/kg) during the cycle test (p < 0.05) and a
higher shuttle-run score (p < 0.05) compared to the slender group. The power
output relative to FFM (W/kg FFM) was comparable (p > 0.05) between different
body build groups. This study showed that body build is an important determinant
of the aerobic test performance. In contrast, there were no differences in
aerobic test performance per kilogramme FFM over the body build groups. This
suggests that the body build may be determined by genetic predisposition. Key
PointsChildren with a solid body build perform better in aerobic exercise tests
than slender children.The power output relative to fat free mass was comparable
in the solid, slender and average group.Besides body composition, body build
should be considered related to other performance measurements.
PMID- 24357969
TI - Mathematics and computers in sport - overview.
PMID- 24357968
TI - Dynamic training volume: a construct of both time under tension and volume load.
AB - The purpose of this study was to investigate the effects of three different
weight training protocols, that varied in the way training volume was measured,
on acute muscular fatigue. Ten resistance-trained males performed all three
protocols which involved dynamic constant resistance exercise of the elbow
flexors. Protocol A provided a standard for the time the muscle group was under
tension (TUT) and volume load (VL), expressed as the product of the total number
of repetitions and the load that was lifted. Protocol B involved 40% of the TUT
but the same VL compared to protocol A; protocol C was equated with protocol A
for TUT but only involved 50% of the VL. Fatigue was assessed by changes in
maximum voluntary isometric force and integrated electromyography (iEMG) between
the pre- and post-training protocols. The results of the study showed that, when
equated for VL, greater TUT produced greater overall muscular fatigue (p <=
0.001) as reflected by the reduction in the force generating capability of the
muscle. When the protocols were equated for TUT, greater VL (p <= 0.01) resulted
in greater overall muscular fatigue. All three protocols resulted in significant
decreases in iEMG (p <= 0.05) but they were not significantly different from each
other. It was concluded that, because of the importance of training volume to
neuromuscular adaptation, the training volume needs to be clearly described when
designing resistance training programs. Key PointsIncrease in either time under
tension (TUT) or volume load (VL) increases the acute fatigue response, despite
being equated for volume (by another method).A potential discrepancy in training
volume may be present with training parameters that fail to control for either
TUT or VL.Neural fatigue may be a contributing factor to the development of
muscular fatigue but is not influenced by various methods of calculating volume
such as TUT or VL.
PMID- 24357970
TI - Heart rate and blood lactate responses to changquan and daoshu forms of modern
wushu.
AB - The development of specific training designed to enhance physiological aspects of
performance relies heavily on the availability of accurate and validity
physiological data. In the combat sport of Wushu, katas are used to develop
aerobic fitness. It is arguably important to assess and monitor heart rate (HR)
and lactate (La) responses when designing effective training programs. The aim of
this pilot study was to investigate heart rate and lactate responses to forms
execution among Wushu combatants. Male elite modern Wushu athletes (n = 4) from a
South Brazilian regional team participated in the study. Athletes were aged 22.5
+/- 2.08 years old and had at least eight years of Wushu experience. Athletes
carried out the Changquan and Daoshu forms in random order, HR and La were
measured pre- and post-exercise. Results indicate that HR was 176 +/- 3 and 176
+/- 2 bpm and La was 4.38 +/- 1.3 and 5.15 +/- 1.07 mmol.l(-1) for Changquan and
Daoshu forms, respectively. There were no significantly differences in HR and La
between the two forms. HR values represent 89.2 +/- 1.1 and 89.1 +/- 1.8% of age
predicted maximal heart rate and lactate was near of 4 mmol.l(-1) point. In
conclusion, training programs to Wushu combatants could target the range of
physiological values cited above with no differences between two forms. Key
PointsHeart rate and lactate responses are not significantly different between
Changquan and Daoshu forms for Wushu combatants.The Wushu katas could be used to
develop aerobic fitness.
PMID- 24357971
TI - Comparison of normalized maximum aerobic capacity and body composition of sumo
wrestlers to athletes in combat and other sports.
AB - Sumo wrestling is unique in combat sport, and in all of sport. We examined the
maximum aerobic capacity and body composition of sumo wrestlers and compared them
to untrained controls. We also compared "aerobic muscle quality", meaning VO2max
normalized to predicted skeletal muscle mass (SMM) (VO2max /SMM), between sumo
wrestlers and controls and among previously published data for male athletes from
combat, aerobic, and power sports. Sumo wrestlers, compared to untrained
controls, had greater (p < 0.05) body mass (mean +/- SD; 117.0 +/- 4.9 vs. 56.1
+/- 9.8 kg), percent fat (24.0 +/- 1.4 vs. 13.3 +/- 4.5), fat-free mass (88.9 +/-
4.2 vs. 48.4 +/- 6.8 kg), predicted SMM (48.2 +/- 2.9 vs. 20.6 +/- 4.7 kg) and
absolute VO2max (3.6 +/- 1.3 vs. 2.5 +/- 0.7 L.min(-1)). Mean VO2max /SMM (ml.kg
SMM(-1).min(-1)) was significantly different (p < 0.05) among aerobic athletes
(164.8 +/- 18.3), combat athletes (which was not different from untrained
controls; 131.4 +/- 9.3 and 128.6 +/- 13.6, respectively), power athletes (96.5
+/- 5.3), and sumo wrestlers (71.4 +/- 5.3). There was a strong negative
correlation (r = - 0.75) between percent body fat and VO2max /SMM (p < 0.05). We
conclude that sumo wrestlers have some of the largest percent body fat and fat
free mass and the lowest "aerobic muscle quality "(VO2max /SMM), both in combat
sport and compared to aerobic and power sport athletes. Additionally, it appears
from analysis of the relationship between SMM and absolute VO2max for all sports
that there is a "ceiling "at which increases in SMM do not result in additional
increases in absolute VO2max. Key PointsSumo wrestlers have a high absolute
VO2max compared to untrained controls.However, sumo wrestlers have a low VO2max
/kg of skeletal muscle mass compared to other combat sports, other strength/power
sports, and untrained controls.The reason for this is unknown, but is probably
related to alterations in sumo skeletal muscle compared to other sports.Based on
the present and previous data, there appears to be a "ceiling "at which increases
in skeletal muscle mass do not result in additional increases in absolute VO2max.
PMID- 24357972
TI - Evidence of nationalistic bias in muaythai.
AB - MuayThai is a combat sport with a growing international profile but limited
research conducted into judging practices and processes. Problems with judging of
other subjectively judged combat sports have caused controversy at major
international tournaments that have resulted in changes to scoring methods.
Nationalistic bias has been central to these problems and has been identified
across a range of sports. The aim of this study was to examine nationalistic bias
in MuayThai. Data were collected from the International Federation of MuayThai
Amateur (IFMA) World Championships held in Almaty, Kazakhstan September 2003 and
comprised of tournament results from 70 A-class MuayThai bouts each judged by
between five and nine judges. Bouts examined featured 62 competitors from 21
countries and 25 judges from 11 countries. Results suggested that nationalistic
bias was evident. The bias observed equated to approximately one round difference
between opposing judges over the course of a bout (a mean of 1.09 (SE=0.50)
points difference between judges with opposing affilations). The number of
neutral judges used meant that this level of bias generally did not influence the
outcome of bouts. Future research should explore other ingroup biases, such as
nearest neighbour bias and political bias as well as investigating the
feasibility adopting an electronic scoring system. Key PointsNationalistic bias
is evident in international amateur MuayThai judging.The impact on the outcome of
bouts is limited.The practice of using a large number of neutral judges appears
to reduce the impact of nationalistic bias.
PMID- 24357973
TI - Participation motivation in martial artists in the west midlands region of
England.
AB - The objectives were to identify the participation motivations and the perceived
importance of certain participation factors in martial artists in the West
Midlands, England, UK. A 28-item adapted version of the Participation Motivation
Questionnaire with additional demographic questions was distributed to 30 martial
arts clubs in the West Midlands region. Eight questions that assessed the
perceived importance for participation of progression through grades, learning
self defence skills, technical ability of instructors, cost of participating,
development of confidence, underpinning philosophy and instructional style were
included. Seventy-five questionnaires were returned from a total of 11 clubs from
across representing practitioners in Tai Chi, Karate, Kung fu, Aikido, Jeet Kune
Do, British Free Fighting, Taekwon-Do and Jujitsu. Results indicated that the
rank order in terms of participation motives was: 1-Affiliation; 2-Friendship; 3
Fitness; 4-Reward/status; 5-Competition; 6-Situational and 7-Skill development.
Participants who trained for more than 4 hours per week placed greater importance
on the underpinning philosophy of the martial art. Findings suggest that whilst
there is a gender discrepancy in participation level, once engaged, females were
equally committed to weekly training. The 'style' of the instructor is of
paramount importance for enhancing student motivation to participate. High volume
practitioners would appear to be fully immersed in the holistic appreciation of
the martial art through increased value placed on its underpinning philosophy.
Key PointsWhilst there is a gender discrepancy in participation level, once
engaged, females were equally committed to weekly training.The four most
important participation motivations evident were 'Affiliation', 'Fitness', 'Skill
Development' and 'Friendship'.The three least influential motives were
'Rewards/status; 'Situational' and 'Competition'. " There were no significant
gender or experience differences for any of the emergent motivational
factors.Instructor 'style' is of paramount importance for enhancing student
motivation to participate.
PMID- 24357974
TI - Relative total body fat and skinfold patterning in filipino national combat sport
athletes.
AB - The purpose of this study was to assess relative total body fat and skinfold
patterning in Filipino national karate and pencak silat athletes. Participants
were members of the Philippine men's and women's national teams in karate (12
males, 5 females) and pencak silat (17 males and 5 females). In addition to age,
the following anthropometric measurements were taken: height, body mass, triceps,
subscapular, supraspinale, umbilical, anterior thigh and medial calf skinfolds.
Relative total body fat was expressed as sum of six skinfolds. Sum of skinfolds
and each individual skinfold were also expressed relative to Phantom height. A
two-way (Sport*Gender) ANOVA was used to determine the differences between men
and women in total body fat and skinfold patterning. A Bonferroni-adjusted alpha
was employed for all analyses. The women had a higher proportional sum of
skinfols (80.19 +/- 25.31 mm vs. 51.77 +/- 21.13 mm, p = 0. 001, eta(2) = 0.275).
The men had a lower proportional triceps skinfolds (-1.72 +/- 0.71 versus - 0.35
+/- 0.75, p < 0.001). Collapsed over gender, the karate athletes (-2.18 +/- 0.66)
had a lower proportional anterior thigh skinfold than their pencak silat
colleagues (-1.71 +/- 0.74, p = 0.001). Differences in competition requirements
between sports may account for some of the disparity in anthropometric
measurements. Key PointsThe purpose of the present investigation was to assess
relative total body fat and skinfold patterning in Filipino national karate and
pencak silat athletes.The results seem to suggest that there was no difference
between combat sports in fatness.Skinfold patterning was more in line with what
was reported in the literature with the males recording lower extremity fat.
PMID- 24357975
TI - Variation in resistive force selection during brief high intensity cycle
ergometry: implications for power assessment and production in elite karate
practitioners.
AB - The purpose of this study was to measure power values generated in elite karate
fighters during brief high intensity cycle ergometry when resistive forces were
derived from total - body mass (TBM) or fat - free mass (FFM). Male international
karate practitioners volunteered as participants (n = 11). Body density was
calculated using hydrostatic weighing procedures with fat mass ascertained from
body density values. Participants were required to pedal maximally on a cycle
ergometer (Monark 864) against randomly assigned loads ranging from 70 g.kg(-1) -
95 g.kg(-1) (using a TBM or FFM protocol) for 8 seconds. The resistive force that
produced the highest peak power output (PPO) for each protocol was considered
optimal. Differences (p < 0.05) in peak power outputs were found between the TBM
and FFM experimental condition (1164 +/- 137 W vs. 1289 +/- 145 W respectively).
Differences were also recorded (p < 0.01) between pedal velocity and applied
resistive forces (127 +/- 8 rpm vs. 142 +/- 7 rpm; 6.6 +/- 1 kg vs. 5.5 +/- 1 kg,
respectively). No differences (p > 0.05) were observed between time to PPO, or
heart rate when the TBM and FFM protocols were compared. The findings of this
study suggest that when high intensity cycle ergometer resistive forces are
derived from FFM, greater peak powers can be obtained consistently in karate
athletes. Resistive forces that relate to the active muscle tissue utilised
during this type of exercise may need to be explored in preference to protocols
that include both lean and fat masses. The findings have implications for both
exercise prescription and the evaluation of experimental results concerning
karate athletes. Key PointsMethods for quantifying and measuring high intensity
performance using high intensity cycle ergometry have received considerable
attention in recent years.The assumption has been that the relationship between
total - body mass (TBM) and fat - free mass (FFM) is the same.However, variations
in body composition between participants may under or over estimate cradle
resistive forces used in high intensity cycle ergometry power assessment.This may
lead to spurious calculations of power.The findings of this study demonstrate
that the total capacity, power and relative contribution of the energy systems
involved during experimental high intensity cycle ergometer exercise need re -
evaluating.
PMID- 24357976
TI - Development of a sports specific aerobic capacity test for karate - a pilot
study.
AB - The purpose of the study was to develop an aerobic fitness assessment test for
competitive Karate practitioners and describe the preliminary findings. Five well
trained, competitive Karate practitioners participated in this study. A protocol
simulating common attack strikes used in competition Karate sparring was
developed from video analysis. In addition, pilot testing established a specific
sequence of strikes and timings to be used in the test. The time to perform the
strike sequence remained the same, whilst the time between strike sequence
performances was progressively reduced. The aim of the test was to increase
intensity of exercise through a decrease in recovery. On two separate occasions,
absolute and relative peak oxygen uptake (VO2peak), peak ventilation (VEpeak),
maximum heart rate (HRM), and time to exhaustion (TE) obtained during the test
were recorded. Subjective feedback provided by the participants was positive in
that participants felt the test accurately simulated actions of a competitive
sparring situation, and as a result athletes felt more motivated to perform well
on this test. There was no significant between test difference in absolute
VO2peak, relative VO2peak, HRM and TE (p > 0.05), indicating a potentially high
reproducibility with the new test for these variables (test 1-test 2 difference
of 0.04 L.min(-1), 1 ml.kg(-1).min(-1), -3 beats.min(-1), and 28 s;
respectively). However, VEpeak displayed potentially less reproducibility due to
a significant difference observed between tests (test 1- test 2 difference of
2.8 L.min(-1), p < 0.05). There was a significant relationship between TE and
relative VO2peak (R(2) = 0.77, p < 0.001). Further developments to the test will
need to address issues with work rate/force output assessment/monitoring. The new
test accurately simulates the actions of competitive Karate sparring. Key
PointsThis is the first attempt at an aerobic fitness test specific to
competitive Karate practitionersAnecdotal reports are that the new test
accurately simulates the actions used in competition KarateRelative VO2peak was
significantly related to time to exhaustion, with 63.5% of the variance in time
to exhaustion attributed to relative VO2peak.Test developments include the use of
force plates and transducers to assess force/power output during the test.
PMID- 24357977
TI - Mood and performance in young malaysian karateka.
AB - In an attempt to test the conceptual model by Lane and Terry, the purposes of
this study were 1) to assess mood states in non-depressed and depressed young
karate athletes; 2) to assess mood states in relation to performance in young
karate athletes. The participants were recruited from the 2004 Malaysian Games
(72 males, 19.20 +/- 1.16 years; 37 females, 18.78 +/- 0.88 years). The athletes
were divided into winners (medalists) and losers. The Brunel Mood Scale (BRUMS)
was administered prior to the start of competition. MANOVA was employed to treat
the data, while Pearson correlations were calculated for mood states in each
depressed mood group and by gender. In terms of non-depressed and depressed mood,
tension in the females was higher in the depressed group (5.61 +/- 3.02 vs. 3.11
+/- 1.90, p = 0.026, eta(2) = 0.133), as was fatigue (3.64 +/- 2.61 vs. 0.89 +/-
1.69, p = 0.006, eta(2) = 0.199). Tension in the males was higher in the
depressed group (4.41 +/- 2.52 vs. 1.50 +/- 1.55, p < 0.001, eta(2) = 0.215), as
was anger (1.43 +/- 1.88 vs. 0.25 +/- 1.00, p = 0.019, eta(2) = 0.076). The
highest associations among mood subscales were between anger and depression (r =
0.57), and between depression and fatigue ( r = 0.55) in depressed males. The
female winning karateka scored higher on anger (3.08 +/- 2.96 vs. 1.29 +/- 2.24,
p = 0.046, eta(2) = 0.109). The highest correlations between mood dimensions in
depressed females were between depression and anger (r = 0.85) and between
depression and confusion (r = 0.85). Contrary to previous research on the
influence of depression on anger, only the female winners scored higher on anger.
Several negative mood dimensions were higher in both male and female depressed
groups, lending some support to the conceptual model advanced by Lane and Terry.
Key PointsTo date, there is no information about the relationship between mood
and martial arts performance in Malaysian athletes.There might be cultural
differences in the way Malaysian athletes respond to psychological
questionnaires.The mood-performance and depressed mood-non-depressed mood
relationships might be mediated by age.
PMID- 24357978
TI - How boxers decide to punch a target: emergent behaviour in nonlinear dynamical
movement systems.
AB - Previous research has shown how dynamical systems theory provides a relevant
framework for investigating decision-making behavior in sport. The aim of this
study was to adopt concepts and tools from nonlinear dynamics in examining
effects of boxer-target distance and perceived punching efficiency on emergent
decision-making during a typical practice task in boxing. Results revealed the
existence of critical values of scaled distances between boxers and targets for
first time appearance and disappearance of a diverse range of boxing actions
including jabs, hooks and uppercuts. Reasons for the diversity of actions were
twofold: i) abrupt (qualitative) changes in the number of the possible punches,
i.e. motor solutions to the hitting task; and ii), fine modification of the
probabilities of selecting specific striking patterns. Boxers were able to
exploit the emerging perception of strikeability, leading to a changing diversity
of selected actions and a cascade of abrupt changes in the perceptual-motor work
space of the task. Perceived efficiency of a punching action by the participants
also changed as a function of the scaled distance to a target and was correlated
with the probability of occurrence of specific boxing actions. Accordingly,
scaled distance-dependent perceived efficiency seems an important perceptual
constraint in the training task of punching a heavy bag in boxers. Key
PointsDuring the practicing with static (i.e. non moving) heavy bags novice
boxers' perceptual-action system is sensitive to the scaled distance and
efficiency informational constraints. These interdependent constraints shape the
action behaviour of the novice boxers;During heavy bag practice novice boxers are
subject to a kind of discovery learning by exploring the efficiency of their
motor repertoire when changing the performer - target distances;The region close
to D = 0.6 maximizes the flexibility of switching among different types of
punching actions and is optimal for practicing the temporal couplings between all
types of boxing actions;Strategic positioning among boxers spontaneously emerges
under the pressure of the key constraints revealed in these research. Applying
practice strategy that emphasizes learning in which trainees would themselves
explore, discover and thus adapt to the information - movement demands of diverse
sparring situations is thus of great importance.
PMID- 24357979
TI - Physiological profile of senior and junior England international amateur boxers.
AB - Despite worldwide popularity of amateur boxing, research focussed on the
physiological demands of the sport is limited. The physiological profile of
Senior and Junior England international amateur boxers is presented. A gradual (8
to 21-days) and rapid (0 to 7-days) phase of body weight reduction was evident
with 2.2 +/- 0.3 % of the 7.0 +/- 0. 8 % weight loss occurring over the final 24
hours. An increase in body weight >4% was observed following a recovery period.
High urine osmolality values (> 1000 mOsm.kg(-1)) were recorded during training
and competition. High post-competition blood lactate values (>13.5 mmol.l(-1))
highlighted the need for a well-developed anaerobic capacity and the importance
of not entering the ring in a glycogen depleted state. The aerobic challenge of
competition was demonstrated by maximum heart rate values being recorded during
'Open' sparring. Mean body fat values of 9-10% were similar to those reported for
other weight classified athletes. Normal resting values were reported for
hematocrit (Senior 48 +/- 2 % and Junior 45 +/- 2 %), haemoglobin (Senior 14.7 +/
1.0 g.dl(-1) and Junior 14.5 +/- 0.8 g.dl(-1)), bilirubin (Senior 15.3 +/- 6.2
umol.l-1(-1)) and ferritin (Senior 63.3 +/- 45.7 ng.ml(-1)). No symptoms
associated with asthma or exercise-induced asthma was evident. A well- developed
aerobic capacity was reflected in the Senior VO2max value of 63.8 +/- 4.8 ml.kg(
1).min(-1). Senior lead hand straight punching force (head 1722 +/- 700 N and
body 1682 +/- 636 N) was lower than the straight rear hand (head 2643 +/- 1273 N
and body 2646 +/- 1083 N), lead hook (head 2412 +/- 813 N and body 2414 +/- 718
N) and rear hook (head 2588 +/- 1040 N and body 2555 +/- 926 N). It was concluded
that amateur boxing performance is dependent on the interplay between anaerobic
and aerobic energy systems. Current weight making methods may lead to impaired
substrate availability, leading to reduced competitive performance and an
increased risk to a boxers health. Key PointsSenior England international amateur
boxers decrease 6.0-8.3 % (7.0 +/- 0.8 %) body weight over a 21-day pre-contest
period by employing passive and active weight making methods.Urine osmolality
values >1000 mOsm.kg(-1) are recorded during training and competition.Senior and
Junior England international amateur boxers experience high post contest blood
lactate values (Seniors 13.5 +/- 2 mmol.l(-1) and Juniors 14.1 +/- 2 mmol.l(-1)
under the current 4 rounds x 2-minute contest format.Senior England international
amateur boxers have a high relative VO2max of 63.8 +/- 4.8 ml.kg(-1).min(
1)Senior England international amateur boxers have a straight and hook punch
force >2400 N, except for the straight lead hand to the head and body.
PMID- 24357980
TI - Study of physiological profile of Indian boxers.
AB - The present study was conducted to study the morphological, physiological and
biochemical characteristics of Indian National boxers as well as to assess the
cardiovascular adaptation to graded exercise and actual boxing round. Two
different studies were conducted. In the first study [N = 60, (junior boxers
below-19 yrs, n = 30), (senior boxers-20-25 yrs, n = 30)] different
morphological, physiological and biochemical parameters were measured. In the
second study (N = 21, Light Weight category- <54 kg, n = 7; Medium weight
category <64 kg, n = 7 and Medium heavy weight category <75 kg, n = 7)
cardiovascular responses were studied during graded exercise protocol and actual
boxing bouts. Results showed a significantly higher (p < 0.05) stature, body
mass, LBM, body fat and strength of back and grip in senior boxers compared to
juniors. Moreover, the senior boxers possessed mesomorphic body conformation
where as the juniors' possessed ectomorphic body conformation. Significantly
lower (p < 0.05) aerobic capacity and anaerobic power were noted in junior boxers
compared to seniors. Further, significantly higher (p < 0.05) maximal heart rates
and recovery heart rates were observed in the seniors as compared to the juniors.
Significantly higher maximum heart rates were noted during actual boxing compared
to graded exercise. Blood lactate concentration was found to increase with the
increase of workload during both graded exercise and actual boxing round. The
senior boxers showed a significantly elevated (p < 0.05) levels of hemoblobin,
blood urea, uric acid and peak lactate as compared to junior boxers. In the
senior boxers significantly lower levels of total cholesterol, triglyceride and
LDLC were observed as compared to junior boxers. No significant change has been
noted in HDLC between the groups. The age and level of training in boxing has
significant effect on Aerobic, anaerobic component. The study of physiological
responses during graded exercise testing may be helpful to observe the
cardiovascular adaptation in boxers. Key PointsStudy on Indian boxersLaboratory
testing.Physical, physiological and biochemical monitoring.Performance analysis
during actual boxing and laboratory testing.
PMID- 24357981
TI - Perceptions of the contribution of psychology to success in elite kickboxing.
AB - The study used semi-structured interviews to explore the views of three high
performance kickboxers regarding the contribution of psychology to the
development and maintenance of expert performance within kickboxing. The results
provide a useful insight into the experiences of high performance kickboxers,
identifying those mental skills and psychological attributes that are perceived
to contribute to success. Participants identified seven mental skills that they
believed to be linked to success in kickboxing; 1) effective use of self-talk, 2)
relaxation, 3) heightened concentration, 4) self-regulation of arousal, 5) goal
setting, 6) coping with being hit, and 7) imagery. Three psychological
characteristics were identified by all participants as contributing to success,
1) high self-efficacy, 2) highly motivated and 3) mental toughness. Although not
specifically identified by participants, it is suggested that a fourth
psychological characteristic was also apparent. Participants demonstrated varying
degrees of emotional intelligence thorough their ability to monitor and
manipulate their emotional states prior to and during competition. Martial
artists used a number of long and short-term psychological strategies in
preparing for competition. Furthermore, whilst mental skills were not
systematically practiced, all participants endeavored to integrate some form of
mental training within physical training. It is recommended that sport
psychologists help martial artists develop and refine individualized mental
training routines, assisting with the formal integration of psychological
training into physical training. Martial artists spend the majority of their time
practicing as opposed to competing. As such, the integration of mental skills
training within physical training may help ensure quality practice, and
facilitate the effective transfer of mental skills into competition. Key
PointsPerceptions of the contribution of psychology to success in high
performance kickboxing was explored using semi-structured interviews.Seven mental
skills and three psychological attributes were collectively identified by
participants, which they perceived as being linked to success.The need to
integrate mental skills training into physical training was identified. This is
necessary to optimise training effectiveness, and as such should be a key
objective of applied sport psychologists.
PMID- 24357982
TI - The importance of isometric maximum strength in college wrestlers.
AB - Previous research has demonstrated the importance of isometric maximal strength
(PF) and rate of force development (RFD) in a variety of athletic populations
including track cyclists and track and field athletes. Among coaches and sports
scientists there is a lack of agreement regarding how much strength is required
for optimal performance in most sports. The purpose of this study was to examine
relationships between measures of PF, RFD and one repetition maximum (1RM)
strength with other variables that might contribute to successful performance in
collegiate wrestlers. Eight men (M = 20.0, SD = 0.4 years; Height M = 1.68, SD =
0. 13 m; Mass M = 78.0, SD = 4.2 kg) who were Division III college wrestlers
participated in this study. They were tested for PF using the isometric mid thigh
pull exercise. Explosive strength was measured as RFD from the isometric force
time curve. The 1RM for the squat, bench press and power clean exercises were
determined as a measure of dynamic strength. Vertical jump height was measured to
determine explosive muscular power. The wrestlers also ranked themselves and the
coaches of the team also provided a ranking of the athletes. Correlations between
the variables were calculated using the Pearson product moment method. Results
indicated strong correlations between measures of PF and 1RM (r = 0.73 - 0.97).
The correlations were very strong between the power clean 1RM and PF (r = 0.97)
and squat 1RM and PF (r = 0.96). There were no other significant correlations
with other variables apart from a strong correlation between RFD and coaches
ranking (r = 0.62). Findings suggest that isometric mid thigh pull test does
correlate well with 1RM testing in college wrestlers. RFD does not appear to be
as important in college wrestlers. The isometric mid thigh pull provides a quick
and efficient method for assessing isometric strength in athletes. This measure
also provides a strong indication of dynamic performance in this population. The
lack of strong correlations with other performance variables may be a result of
the unique metabolic demands of wrestling. Key PointsIn Division III collegiate
wrestlers the isometric mid thigh pull test correlates well with 1RM testing.Rate
of Force Development does not appear to be as important in college wrestlers.The
lack of strong correlations with other performance variables may be a result of
the unique metabolic demands of wrestling.
PMID- 24357983
TI - A profile of olympic taekwondo competitors.
AB - The purpose of this study was to identify the profile of the Olympic champions
and the other competitors who were involved in the Games. The information on each
of the athletes was obtained from the "Official Site of the Sydney 2000 Olympic
Games, www.olympics.com/eng/sports/TK "and included weight category, weight,
height, age, points obtained, warnings, deduction point, defensive/offensive
kicks and punches. One hundred and two athletes competed (54 males and 48
females) in the Games. The mean average age and BMI (Body Mass Index) of 16 male
winners was 24.4 +/- 3.3 years and 21.9 +/- 2.4 respectively compared to 25.2 +/-
4.3 years and 22.8 +/- 3.3 for the 38 male non-winners. The mean average age and
BMI of the 16 female winners was 23.1 +/- 3.9 years and 20.8 +/- 2.3 respectively
compared to 24.9 +/- 4.7 years and 21.3 +/- 2.7 for the 32 female non-winners.
For all four types of athletes, offensive kicks accounted for at least 52% of the
techniques to score a point. Ninety-eight percent of all techniques used to score
were kicks. Although not statistically significant, winners overall tended to be
younger in age and taller with slightly lower BMI than their weight category
average. Taking into account the literature cited in this article, future studies
should be designed to examine the relationship between performance and functional
variables such as muscle power, muscle endurance, reaction time and aerobic
capacity. Key PointsWinners tended to be younger in age and taller with slightly
lower BMI than their weight category average.An offensive technique was used to
score slightly more often than a defensive one.Overall, 98% of all techniques
used to score were kicks.
PMID- 24357984
TI - A three-dimensional analysis of the center of mass for three different judo
throwing techniques.
AB - Four black belt throwers (tori) and one black belt faller (uke) were filmed and
analyzed in three-dimensions using two video cameras (JVC 60 Hz) and motion
analysis software. Average linear momentum in the anteroposterior (x), vertical
(y), and mediolateral (z) directions and average resultant impulse of uke's
center of mass (COM) were investigated for three different throwing techniques;
harai-goshi (hip throw), seoi-nage (hand throw), and osoto-gari (leg throw). Each
throw was broken down into three main phases; kuzushi (balance breaking), tsukuri
(fit-in), and kake (throw). For the harai-goshi and osoto-gari throws, impulse
measurements were the largest within kuzushi and tsukuri phases (where collision
between tori and uke predominantly occurs). Both throws indicated an importance
for tori to create large momentum prior to contact with uke. The seoi-nage throw
demonstrated the lowest impulse and maintained forward momentum on the body of
uke throughout the entire throw. The harai-goshi and osoto-gari are considered
power throws well-suited for large and strong judo players. The seoi-nage throw
is considered more technical and is considered well-suited for shorter players
with good agility. A form of resistance by uke was found during the kuzushi phase
for all throws. The resistance which can be initiated by tori's push or pull
allows for the tsukuri phase to occur properly by freezing uke for a good fit-in.
Strategies for initiating an effective resistance include initiating movement of
uke so that their COM is shifted to their left (for right handed throw) by
incorporating an instantaneous "snap pull "with the pulling hand during kuzushi
to create an opposite movement from uke. Key PointsThe degree of collision
between the thrower (tori) and person being thrown (uke) may be a reflection of
throwing power.The hip throw (harai-goshi) and leg throw (osoto-gari) created
large collisions onto uke and are considered power throws well-suited for
stronger and heavier players.The shoulder throw (seio-nage) created small
collisions onto uke emphasizing the importance for skill rather than strength.A
theoretical resistance to tori's pull was found during the kuzushi phase
indicating a propensity for uke to freeze and allow tori to better fit into the
throw during the tsukuri phase.
PMID- 24357985
TI - The progress achieved by judokas after strength training with a judo-specific
machine.
AB - For judo players, as in many sports activities, strength development has become
an important element of performance. However, this should not be done separately
from the development of technique. Specific strength training is thus used for
the controlled strengthening of specific muscles or muscle groups, corresponding
to the movement in a competitive situation. In line with this, the use of a judo
specific apparatus is proposed. The aim of this study is to analyze the progress
of a group of judokas after a training program with the apparatus. The results
have shown that, using the apparatus, the heaviest weight achieved using the
throwing technique is greater. In addition, the judokas' technique improves as a
consequence of this training program. This judo specific apparatus could
therefore be used to complement traditional judo training. Key PointsJudo,
strength training, machine, technical progress.
PMID- 24357986
TI - Incidence of injury in professional mixed martial arts competitions.
AB - Mixed Martial Arts (MMA) competitions were introduced in the United States with
the first Ultimate Fighting Championship (UFC) in 1993. In 2001, Nevada and New
Jersey sanctioned MMA events after requiring a series of rule changes. The
purpose of this study was to determine the incidence of injury in professional
MMA fighters. Data from all professional MMA events that took place between
September 2001 and December 2004 in the state of Nevada were obtained from the
Nevada Athletic Commission. Medical and outcome data from events were analyzed
based on a pair-matched case-control design. Both conditional and unconditional
logistic regression models were used to assess risk factors for injury. A total
of 171 MMA matches involving 220 different fighters occurred during the study
period. There were a total of 96 injuries to 78 fighters. Of the 171 matches
fought, 69 (40.3%) ended with at least one injured fighter. The overall injury
rate was 28.6 injuries per 100 fight participations or 12.5 injuries per 100
competitor rounds. Facial laceration was the most common injury accounting for
47.9% of all injuries, followed by hand injury (13.5%), nose injury (10.4%), and
eye injury (8.3%). With adjustment for weight and match outcome, older age was
associated with significantly increased risk of injury. The most common
conclusion to a MMA fight was a technical knockout (TKO) followed by a tap out.
The injury rate in MMA competitions is compatible with other combat sports
involving striking. The lower knockout rates in MMA compared to boxing may help
prevent brain injury in MMA events. Key PointsMixed martial arts (MMA) has
changed since the first MMA matches in the United States and now has increased
safety regulations and sanctioning.MMA competitions have an overall high rate of
injury.There have been no MMA deaths in the United States.The knockout (KO) rate
in MMA appears to be lower than the KO rate of boxing matches.MMA must continue
to be supervised by properly trained medical professionals and referees to ensure
fighter safety in the future.
PMID- 24357987
TI - Mood profiling during olympic qualifying judo competition: a case study testing
transactional relationships.
AB - This case study investigated relationships between personality, mood states
changes, coping strategies, self-set goals, and self-efficacy in an elite judo
player. A transactional perspective of psychological responses over time was used
to guide data analysis. The ambient mood is proposed to contribute to the
interpretation of, and reaction to, events during competition, which lead to
subsequent emotional responses. A male international Judo player completed a
number of self-report measures before and during a 4-contest tournament. Measures
included the EPQ, MCOPE, Brunel Mood Scale, self-set goals, and self-efficacy for
goal attainment. State measures were completed after every contest. Results
indicated high scores of self-efficacy to achieve performance goals and outcome
goals. Pre-competition mood results indicated high scores on the Vigor and Anger
subscales with moderate scores for Tension, and zero scores for Depressed mood, a
mood profile that remained relatively stable after winning his first two
contests. After losing his third contest, he reported symptoms of Depressed mood
and indicated using self-blame as coping strategy during the contest. Before the
fourth contest, he coped by using planning and increasing effort. These coping
strategies were associated with reductions in Depressed mood and increases in
Vigor. After finding out his next contest was against a former World Championship
bronze medalist, self-set goals became performance and process with no outcome
goal. On losing this contest, scores on the Anger and Depression subscales
increased sharply, Fatigue scores increased slightly and Tension and Vigor
reduced. Self-blame was used as a coping strategy when experiencing unpleasant
emotions. Findings suggest that self-blame was associated with negative
psychological states comprising depressed mood. Increasing effort and planning
were associated with positive psychological states. Collectively, findings
emphasize the value of using a transactional design to explore mood changes over
time, and future research should investigate the effectiveness of applied
interventions. Key PointsFindings demonstrate the transient nature of mood states
during competition.The paper proposes a transactional model of mood, which
facilitates the exploration of mood changes over time.Mood states at one point in
time will influence the interpretation of situational factors, which combine with
emotional responses to form subsequent mood states.Findings support the notion
that a difference between the perceived progress toward a goal and the internally
expected rate of progress will elicit an emotional response.
PMID- 24357988
TI - Introduction to the special issue on combat sport.
PMID- 24357989
TI - Total synthesis of (+)-antofine and (-)-cryptopleurine.
AB - The tylophorine alkaloid anticancer compounds antofine and cryptopleurine have
been synthesized in optically active form. Both syntheses employ optically pure
alpha-amino acids as the starting materials, require only seven steps from known
2-ethynylpyrrolidine or 2-ethynylpiperidine derivatives, and are free of
protecting groups. Key steps include an alkyne hydration and a chromium carbene
complex based net [5+5]-cycloaddition step. Alkyne hydration was accompanied by
racemization of the resulting beta-aminoketone under most of the conditions
examined, and successful minimization of this side reaction was achieved through
careful pH control and choice of metal additive. Final ring closure involves a
Bischler-Napieralski reaction using a carbamate (antofine) or urea
(cryptopleurine) precursor.
PMID- 24357990
TI - From the Editor's Desk.
PMID- 24357991
TI - Advancing evidence-based practice - a quarterly compilation of research updates
most likely to change clinical practice.
PMID- 24357992
TI - Bioethics in practice - a quarterly column about medical ethics: ethics of chart
review research.
PMID- 24357994
TI - Editorial - reflections on a professional career blessed with teachers, mentors,
and role models.
PMID- 24357993
TI - Clinical images - a quarterly column: early presentation of h-type
tracheoesophageal fistula.
PMID- 24357995
TI - The role of combined assessment in preoperative axillary staging.
AB - BACKGROUND: Axillary lymph node status is the most significant single prognostic
factor in breast cancer, and preoperative axillary staging is essential in
determining lymph node status. Axillary ultrasound scan (AUS) is the gold
standard modality in preoperative staging. However, triple assessment-including
clinical examination and radiological assessment with fine needle aspiration
(FNA) with or without core biopsy-ensures high sensitivity. METHODS: Our study
included 219 women diagnosed with invasive breast cancer between 2009 and 2010.
All patients underwent a preoperative staging AUS that was graded from normal
(U1) to malignant (U5). All patients with ultrasound scans graded U3
(indeterminate) and above underwent FNA that was graded from C1 (inadequate for
diagnosis) to C5 (malignant). Patients diagnosed preoperatively with metastatic
lymph nodes were offered axillary lymph node clearance. The rest of the patients
were offered sentinel lymph node biopsy. RESULTS: The 219 women were diagnosed
with 228 invasive breast cancers. The mean age was 60 years (range 29-90 years).
The final histology report showed metastatic axillary lymph nodes in 49 (21.5%)
cases. Of these 49 cases, 22 were diagnosed preoperatively with metastatic
axillary lymph node and were elected for axillary lymph node clearance, and 27
were elected for sentinel lymph node biopsy that revealed metastatic lymph nodes.
AUS showed abnormal (U3/U4/U5) axillary lymph nodes in 30 of 49 (61.2%) cancer
cases with an overall accuracy of 91.6%. CONCLUSION: Combined triple assessment
increases the sensitivity, negative predictive value, and overall accuracy of
preoperative staging of the axilla.
PMID- 24357996
TI - Effects of thiamine on cardiac function in patients with systolic heart failure:
systematic review and metaanalysis of randomized, double-blind, placebo
controlled trials.
AB - BACKGROUND: Thiamine is an important micronutrient, and thiamine deficiency is
prevalent in patients with congestive heart failure. METHODS: Using Ovid MEDLINE,
PubMed, and Excepta Medica (Embase), we conducted a systematic review and
metaanalysis of randomized, double-blind, placebo-controlled trials of thiamine
supplementation in patients with congestive heart failure. RESULTS: Compared with
placebo (2 trials, n=38), thiamine supplementation resulted in a significantly
improved net change in left ventricular ejection fraction (LVEF) (3.28%, 95%
confidence interval [CI]: 0.64%, 5.93%). CONCLUSION: Compared against placebo,
thiamine supplementation in 2 randomized, double-blind trials resulted in a
significant improvement in net change in LVEF. While further trials are required
to establish thiamine's role in patients with systolic heart failure, thiamine
may help to improve LVEF in these patients.
PMID- 24357997
TI - Pulsed Doppler in simulated compartment syndrome: a pilot study to record
hemodynamic compromise.
AB - BACKGROUND: Acute compartment syndrome occurs when the tissue pressure within a
closed muscle compartment exceeds the perfusion pressure. We observed diastolic
retrograde arterial flow (DRAF) in 2 patients in the arteries proximal to
compartment syndromes in injured limbs. We hypothesized that DRAF may represent
an early sign of compartment pressure increments. METHODS: We mimicked
compartment syndrome by using a cuff to produce external compression of the
forearm at increasing pressures. We correlated the applied pressure with brachial
artery blood flow, velocities, and retrograde flow. We studied the brachial
artery at baseline, at external compression of 40 mmHg applied to the forearm, at
forearm compression equal to the patient's diastolic blood pressure (DBP), and at
forearm compression equal to the patient's mean arterial pressure (MAP).
Evaluations included Doppler velocities and DRAF percentage (%). Using a ROC
analysis, we selected a DRAF (%) cutoff value for the identification of patients
with an applied external pressure equal to or greater than their DBP and
calculated its sensitivity and specificity. RESULTS: Compared with baseline, DRAF
(%) was increased at 40 mmHg (P<0.05), at DBP (P<0.05), and at MAP (P<0.05). DRAF
(%) was strongly correlated with applied external pressure (r=0.92, r(2)=0.85).
DRAF 40% presented a 100% sensitivity and a 93% specificity for identifying a
compression equal to or greater than the patient's DBP. CONCLUSION: DRAF (%)
strongly correlates with the degree of external pressure applied to the brachial
artery, suggesting it may represent a useful tool in the detection and evaluation
of compartment syndrome.
PMID- 24357998
TI - The etiology of enterocutaneous fistula predicts outcome.
AB - BACKGROUND: The management of enterocutaneous fistula (ECF) provides a supreme
challenge for the general surgeon. METHODS: We conducted a retrospective review
of all cases of patients with ECF referred to the surgical service from July 2007
to June 2011 to achieve a better understanding of the factors that predict a
successful outcome. RESULTS: A total of 35 patients were evaluated and managed in
a systematic fashion that focused on treatment of abdominal sepsis, control of
fistula output and wound management, nutritional optimization, and operative
intervention when necessary. Age, gender, preoperative laboratory values,
etiology of ECF, and prior abdominal surgery for ECF were reviewed and compared.
Fisher exact test was used to compare patients who achieved a good outcome (n=23)
to those with a poor outcome (n=12) to determine factors that might predict their
ultimate result. Two factors that predicted poor outcome were the presence of
abdominal malignancy (P=0.01) and ECFs that occurred in trauma patients with an
open abdomen (P=0.03). CONCLUSION: The etiology of ECF proved to be a more
reliable predictor of outcome than clinical indicators.
PMID- 24357999
TI - Restorative proctocolectomy: the current ochsner experience.
AB - BACKGROUND: Restorative proctocolectomy with an ileal pouch-anal anastomosis is a
technically demanding procedure to treat ulcerative colitis and familial
adenomatous polyposis. Since its initial description almost 30 years ago, the
operation has undergone technical and perioperative modifications to improve the
patient's experience. METHODS: We performed a retrospective review of the records
of patients undergoing restorative proctocolectomy at the Ochsner Clinic
Foundation Hospital from 2008 to 2012 and compared data from that period to data
from 1989-1995 (prior to laparoscopic pouch surgery) to determine factors
associated with patient outcome. RESULTS: Ileal pouch-anal procedures were
performed in 77 patients. The 30 male and 47 female patients ranged in age from
13 to 63 years (mean, 34.5 years). The indications for the procedure were
ulcerative colitis in 62 patients, polyposis coli in 12 patients, and Crohn
disease in 3 patients. Forty patients (52%) had laparoscopic-assisted procedures.
The overall hospital length of stay for pouch creation averaged 6.9 days (range 3
29) and for ileostomy closure averaged 4.3 days (range 1-15). No perioperative
deaths occurred within 30 days. Complications occurred in 37.7% of patients.
Compared to a previous report of 72 patients from 1989 to 1995, the recent group
had more laparoscopic procedures, shorter hospital stays, a smaller percentage of
3-stage procedures, and fewer general and pouch-related complications. Pouch
failures were similar for both groups. CONCLUSION: Advances in operative
techniques and perioperative management have improved the outcome of restorative
proctocolectomies.
PMID- 24358000
TI - Anesthetic considerations in robotic-assisted gynecologic surgery.
AB - BACKGROUND: Robotic-assisted surgery has evolved over the past 2 decades with
constantly improving technology that assists surgeons in multiple subspecialty
disciplines. The surgical requirements of lithotomy and steep Trendelenburg
positions, along with the creation of a pneumoperitoneum and lack of direct
access to the patient all present management challenges in gynecologic surgery.
Patient positioning requirements can have significant physiologic effects and can
result in many complications. METHODS: This review focuses on the anesthetic and
surgical implications of robot-assisted technology in gynecologic surgery.
CONCLUSION: Good communication among team members and knowledge of the nuances of
robotic surgery have the potential to improve patient outcomes, increase
efficiency, and reduce complications.
PMID- 24358001
TI - Basic concepts in opioid prescribing and current concepts of opioid-mediated
effects on driving.
AB - BACKGROUND: Many patients with chronic pain receive substandard analgesic
therapy. Incomplete or inadequate care often stems from physician fears of
patient addiction and/or drug toxicity. As a result, many chronic pain patients
are undertreated and have unrelieved pain that tempts them to overuse or to abuse
prescribed pharmacologic treatments. In the last few years, educational efforts
have targeted physicians who treat chronic, nonmalignant pain with information to
improve prescribing strategies and to appreciate side effects. Additionally,
opioid prescribing guidelines and educational programs, including World Health
Organization-published guidelines for the management of cancer pain in 1986 and
the American Pain Society's promotion of pain as the 5(th) vital sign, have
increased the propensity of pharmacists, physicians, and pain specialists to
dispense pain treatments. METHODS: Controversial and evolving consequences from
this explosion of prescription opioid use have emerged and are discussed in this
review, including prescribing principles, opioid analgesic side effects, and
driving concerns. CONCLUSION: With additional appreciation for the untoward
effects of chronic analgesia and a better understanding of opioid pharmacology,
physicians can utilize pain management treatments in a safer and more effective
manner.
PMID- 24358002
TI - Serotonin syndrome.
AB - BACKGROUND: Serotonin syndrome is a potentially life-threatening syndrome that is
precipitated by the use of serotonergic drugs and overactivation of both the
peripheral and central postsynaptic 5HT-1A and, most notably, 5HT-2A receptors.
This syndrome consists of a combination of mental status changes, neuromuscular
hyperactivity, and autonomic hyperactivity. Serotonin syndrome can occur via the
therapeutic use of serotonergic drugs alone, an intentional overdose of
serotonergic drugs, or classically, as a result of a complex drug interaction
between two serotonergic drugs that work by different mechanisms. A multitude of
drug combinations can result in serotonin syndrome. METHODS: This review
describes the presentation and management of serotonin syndrome and discusses the
drugs and interactions that can precipitate this syndrome with the goal of making
physicians more alert and aware of this potentially fatal yet preventable
syndrome. CONCLUSION: Many commonly used medications have proven to be the
culprits of serotonin syndrome. Proper education and awareness about serotonin
syndrome will improve the accuracy of diagnosis and promote the institution of
the appropriate treatment that may prevent significant morbidity and mortality.
PMID- 24358003
TI - Dexmedetomidine for anterior mediastinal mass computed tomography-guided biopsy:
a case series.
AB - BACKGROUND: Sedation of children undergoing biopsies of anterior mediastinal
masses can be challenging because of the absolute necessity of ensuring minimal
smooth muscle relaxation and preventing airway collapse. Furthermore, positive
pressure ventilation may be difficult or impossible and may also pose the
additional risks of hemodynamic compromise in the pediatric patient. CASE
REPORTS: We present a case series of 3 children who were successfully sedated for
computed tomography (CT)-guided mediastinal biopsies with dexmedetomidine.
CONCLUSION: Dexmedetomidine, a selective alpha-2 adrenoreceptor agonist that
maintains the smooth musculature of the pediatric airway, provides the ability to
sustain spontaneous ventilation in patients with airway compression.
Dexmedetomidine is a safe, reliable anesthetic for biopsy of children with
anterior mediastinal masses.
PMID- 24358004
TI - Onset of lone atrial fibrillation during labor under epidural analgesia.
AB - BACKGROUND: Practice standards recommend that the induction of epidural analgesia
for labor begin with a test dose of local anesthetic with epinephrine. During the
test dose period and following anesthetic administration, the anesthesiologist
measures the parturient's pulse with continuous pulse oximetry to help detect the
intravascular placement of the epidural catheter as evidenced by the abrupt onset
of tachycardia. CASE REPORT: We report the onset of tachycardia in a healthy
parturient following induction of continuous epidural analgesia. The tachycardia
was ultimately diagnosed as lone atrial fibrillation-a finding not previously
reported in the literature. CONCLUSION: We initially thought the diagnosis
portended undetected cardiac disease, but further assessment found no cardiac
abnormalities.
PMID- 24358005
TI - Traumatic tibia and fibula fracture in a 36 weeks' pregnant patient: a case
report.
AB - BACKGROUND: Bone fracture management in third-trimester pregnant patients is rare
and poorly discussed in the literature. In the case of fractures that require
orthopedic surgery in near-term pregnant women, clinicians should decide between
operating before or after the delivery, carefully evaluating the health of the
mother and fetus. CASE REPORT: A pregnant 41-year-old woman at 36 weeks'
gestation had a traumatic midshaft displaced tibia and fibula fracture. A
multispecialty team approach resulted in nonoperative treatment until delivery.
The sudden spontaneous premature rupture of membranes led to a preterm cesarean
section. Five days after cesarean section, the patient underwent surgery for open
reduction and internal fixation with pins and plates. The patient recovered well
and was discharged with her baby. CONCLUSION: The clinical and surgical
management of bone fractures in pregnant women should be determined by a
multispecialty team, and a tailored intervention should be chosen for each
patient.
PMID- 24358006
TI - A case of teeth discoloration upon transition from zyprexa to generic olanzapine.
AB - BACKGROUND: Although crucial to the success of the US healthcare system, generic
medication is not without some risks, especially when a transition is made
midtreatment from a brand-name formulation to its generic counterpart.
Thankfully, such a transition is usually orderly and unnoticed, without
disruption to the treatment; however, this is not always the case. CASE REPORT:
This case study details an example of 1 such unfortunate disruption to treatment.
A stable patient with schizophrenia was switched from brand-name Zyprexa to
generic olanzapine. Within several months of the switch, the patient suffered a
marked grayish discoloration of his teeth. His medication regimen was then
transitioned from generic olanzapine to a new but different brand-name medication
(Abilify). The transition was a success, with resolution of the adverse effect
and continued stability of his mental state. CONCLUSION: Generic olanzapine was
introduced to the market in fall 2011. It remains to be seen whether this adverse
effect was simply an anomaly or the beginning of a more ominous trend.
PMID- 24358007
TI - Multiple myeloma relapse following autologous stem cell transplant presenting
with diffuse pulmonary nodules.
AB - BACKGROUND: Multiple myeloma is a common disease, accounting for about 10% of
hematologic malignancies in the United States. For eligible patients, the
treatment of choice includes induction therapy (usually involving newer biologic
agents) followed by autologous stem cell transplant; however, this treatment is
generally not considered curative, and relapses usually occur. However,
extramedullary relapse is an uncommon presentation, and relapses that involve the
lungs have only rarely been described. CASE REPORT: We report the case of a
patient who underwent an autologous stem cell transplant for multiple myeloma and
subsequently relapsed with diffuse pulmonary nodules. She then had a rapid
clinical and serologic response following initiation of salvage therapy.
CONCLUSION: This case is remarkable for both the radiographic appearance of the
pulmonary involvement, as well as the rapid resolution of these findings after 2
cycles of treatment with bortezomib, dexamethasone, and lenalidomide.
PMID- 24358008
TI - Report of seizure following intraoperative monitoring of transcranial motor
evoked potentials.
AB - BACKGROUND: Transcranial motor evoked potentials are used to detect iatrogenic
injury to the corticospinal tracts and vascular territory of the anterior spinal
artery. Tongue and lip lacerations are the most common complication of this
modality. Theoretical complications include cardiac arrhythmia and seizure
although there are no published reports of either. CASE REPORT: We report a case
of postoperative seizure following motor evoked potential testing in a patient
without a seizure history. Although anecdotal reports exist, ours is the first
known published report of seizure following transcranial electrical stimulation.
CONCLUSION: The intent of this novel report is to encourage the use of anesthetic
regimens that raise seizure threshold, decrease stimulation threshold, and
increase the specificity of motor evoked potentials. Providers should be prepared
to treat intraoperative or perioperative seizure activity when the monitoring
protocol includes transcranial motor evoked potentials.
PMID- 24358009
TI - Median arcuate ligament syndrome: a case report.
AB - BACKGROUND: The median arcuate ligament passes superior to the origin of the
celiac artery and is a continuation of the posterior diaphragm that wraps over
the aorta. If it lies too low on the aorta, the ligament may cause symptoms of
abdominal pain related to compression of the celiac artery. CASE REPORT: An
abdominal ultrasound in a 22-year-old woman with longstanding abdominal pain
after eating showed elevated celiac artery velocities of >300 cm/s upon
inspiration. Computed tomography angiography of the abdomen showed stenosis of
the origin of the celiac artery and confirmed the diagnosis of median arcuate
ligament syndrome. Laparoscopic release of the median arcuate ligament resulted
in relief of the patient's symptoms. CONCLUSION: The diagnosis of median arcuate
ligament syndrome should be considered in patients with postprandial abdominal
pain that does not have a clearly established etiology.
PMID- 24358010
TI - Guess the case.
PMID- 24358011
TI - Letters to the editor.
PMID- 24358013
TI - Editorial consultants 2013.
PMID- 24358014
TI - CME Upcoming Events/CME Credit Information.
PMID- 24358012
TI - Recent publications by ochsner authors.
PMID- 24358015
TI - CME Test/CME Application Form.
PMID- 24358016
TI - Finding the signal by adding noise: The role of noncontrastive phonetic
variability in early word learning.
AB - It is well attested that 14-month olds have difficulty learning similar sounding
words (e.g. bih/dih), despite their excellent phonetic discrimination abilities.
In contrast, Rost and McMurray (2009) recently demonstrated that 14-month olds'
minimal pair learning can be improved by the presentation of words by multiple
talkers. This study investigates which components of the variability found in
multi-talker input improved infants' processing, assessing both the
phonologically contrastive aspects of the speech stream and phonologically
irrelevant indexical and suprasegmental aspects. In the first two experiments,
speaker was held constant while cues to word-initial voicing were systematically
manipulated. Infants failed in both cases. The third experiment introduced
variability in speaker, but voicing cues were invariant within each category.
Infants in this condition learned the words. We conclude that aspects of the
speech signal that have been typically thought of as noise are in fact valuable
information - signal - for the young word learner.
PMID- 24358017
TI - Household chaos moderates the link between maternal attribution bias and
parenting: Parenting: Science and Practice.
AB - OBJECTIVE: Parents who attribute child misbehavior to children's intentions and
dismiss situational factors tend to show more hostility and less warmth in their
parenting behavior, and are at greater risk for maltreatment. We extended this
literature by investigating the role of household chaos as a moderator of the
link between maternal attribution biases and parenting behaviors. DESIGN: The
current sample included 160 mothers of 3- to7-year-old children. Mothers provided
reports on their attribution biases and household chaos levels. Maternal
negativity and positivity were measured using self-reports and observers'
ratings. RESULTS: The links between attribution bias and parenting behavior were
stronger in more chaotic environments, with the moderating effect of chaos being
particularly strong for internal attribution bias. CONCLUSIONS: The findings
point to the importance of social cognitive biases in the etiology of maternal
behavior in family contexts that lack order and predictability.
PMID- 24358018
TI - Cluster Analysis: Unsupervised Learning via Supervised Learning with a Non-convex
Penalty.
AB - Clustering analysis is widely used in many fields. Traditionally clustering is
regarded as unsupervised learning for its lack of a class label or a quantitative
response variable, which in contrast is present in supervised learning such as
classification and regression. Here we formulate clustering as penalized
regression with grouping pursuit. In addition to the novel use of a non-convex
group penalty and its associated unique operating characteristics in the proposed
clustering method, a main advantage of this formulation is its allowing borrowing
some well established results in classification and regression, such as model
selection criteria to select the number of clusters, a difficult problem in
clustering analysis. In particular, we propose using the generalized cross
validation (GCV) based on generalized degrees of freedom (GDF) to select the
number of clusters. We use a few simple numerical examples to compare our
proposed method with some existing approaches, demonstrating our method's
promising performance.
PMID- 24358020
TI - Heat shock response regulator is pinned to the membrane.
PMID- 24358019
TI - Heat shock transcription factor sigma32 co-opts the signal recognition particle
to regulate protein homeostasis in E. coli.
AB - All cells must adapt to rapidly changing conditions. The heat shock response
(HSR) is an intracellular signaling pathway that maintains proteostasis (protein
folding homeostasis), a process critical for survival in all organisms exposed to
heat stress or other conditions that alter the folding of the proteome. Yet
despite decades of study, the circuitry described for responding to altered
protein status in the best-studied bacterium, E. coli, does not faithfully
recapitulate the range of cellular responses in response to this stress. Here, we
report the discovery of the missing link. Surprisingly, we found that sigma(32),
the central transcription factor driving the HSR, must be localized to the
membrane rather than dispersed in the cytoplasm as previously assumed. Genetic
analyses indicate that sigma(32) localization results from a protein targeting
reaction facilitated by the signal recognition particle (SRP) and its receptor
(SR), which together comprise a conserved protein targeting machine and mediate
the cotranslational targeting of inner membrane proteins to the membrane. SRP
interacts with sigma(32) directly and transports it to the inner membrane. Our
results show that sigma(32) must be membrane-associated to be properly regulated
in response to the protein folding status in the cell, explaining how the HSR
integrates information from both the cytoplasm and bacterial cell membrane.
PMID- 24358021
TI - Polycomb protein SCML2 regulates the cell cycle by binding and modulating
CDK/CYCLIN/p21 complexes.
AB - Polycomb group (PcG) proteins are transcriptional repressors of genes involved in
development and differentiation, and also maintain repression of key genes
involved in the cell cycle, indirectly regulating cell proliferation. The human
SCML2 gene, a mammalian homologue of the Drosophila PcG protein SCM, encodes two
protein isoforms: SCML2A that is bound to chromatin and SCML2B that is
predominantly nucleoplasmic. Here, we purified SCML2B and found that it forms a
stable complex with CDK/CYCLIN/p21 and p27, enhancing the inhibitory effect of
p21/p27. SCML2B participates in the G1/S checkpoint by stabilizing p21 and
favoring its interaction with CDK2/CYCE, resulting in decreased kinase activity
and inhibited progression through G1. In turn, CDK/CYCLIN complexes phosphorylate
SCML2, and the interaction of SCML2B with CDK2 is regulated through the cell
cycle. These findings highlight a direct crosstalk between the Polycomb system of
cellular memory and the cell-cycle machinery in mammals.
PMID- 24358022
TI - Stem cell transplantation in traumatic spinal cord injury: a systematic review
and meta-analysis of animal studies.
AB - Spinal cord injury (SCI) is a devastating condition that causes substantial
morbidity and mortality and for which no treatments are available. Stem cells
offer some promise in the restoration of neurological function. We used
systematic review, meta-analysis, and meta-regression to study the impact of stem
cell biology and experimental design on motor and sensory outcomes following stem
cell treatments in animal models of SCI. One hundred and fifty-six publications
using 45 different stem cell preparations met our prespecified inclusion
criteria. Only one publication used autologous stem cells. Overall, allogeneic
stem cell treatment appears to improve both motor (effect size, 27.2%; 95%
Confidence Interval [CI], 25.0%-29.4%; 312 comparisons in 5,628 animals) and
sensory (effect size, 26.3%; 95% CI, 7.9%-44.7%; 23 comparisons in 473 animals)
outcome. For sensory outcome, most heterogeneity between experiments was
accounted for by facets of stem cell biology. Differentiation before implantation
and intravenous route of delivery favoured better outcome. Stem cell implantation
did not appear to improve sensory outcome in female animals and appeared to be
enhanced by isoflurane anaesthesia. Biological plausibility was supported by the
presence of a dose-response relationship. For motor outcome, facets of stem cell
biology had little detectable effect. Instead most heterogeneity could be
explained by the experimental modelling and the outcome measure used. The
location of injury, method of injury induction, and presence of immunosuppression
all had an impact. Reporting of measures to reduce bias was higher than has been
seen in other neuroscience domains but were still suboptimal. Motor outcomes
studies that did not report the blinded assessment of outcome gave inflated
estimates of efficacy. Extensive recent preclinical literature suggests that stem
cell-based therapies may offer promise, however the impact of compromised
internal validity and publication bias mean that efficacy is likely to be
somewhat lower than reported here.
PMID- 24358023
TI - Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent
mitotic spindle orientation in proliferating hepatocytes.
AB - The development and maintenance of polarized epithelial tissue requires a tightly
controlled orientation of mitotic cell division relative to the apical polarity
axis. Hepatocytes display a unique polarized architecture. We demonstrate that
mitotic hepatocytes asymmetrically segregate their apical plasma membrane domain
to the nascent daughter cells. The non-polarized nascent daughter cell can form a
de novo apical domain with its new neighbor. This asymmetric segregation of
apical domains is facilitated by a geometrically distinct "apicolateral"
subdomain of the lateral surface present in hepatocytes. The polarity protein
partitioning-defective 1/microtubule-affinity regulating kinase 2 (Par1b/MARK2)
translates this positional landmark to cortical polarity by promoting the
apicolateral accumulation of Leu-Gly-Asn repeat-enriched protein (LGN) and the
capture of nuclear mitotic apparatus protein (NuMA)-positive astral microtubules
to orientate the mitotic spindle. Proliferating hepatocytes thus display an
asymmetric inheritance of their apical domains via a mechanism that involves
Par1b and LGN, which we postulate serves the unique tissue architecture of the
developing liver parenchyma.
PMID- 24358024
TI - Restoring vision through "Project Prakash": the opportunities for merging science
and service.
PMID- 24358025
TI - Deducing protein function by forensic integrative cell biology.
AB - Our ability to sequence genomes has provided us with near-complete lists of the
proteins that compose cells, tissues, and organisms, but this is only the
beginning of the process to discover the functions of cellular components. In the
future, it's going to be crucial to develop computational analyses that can
predict the biological functions of uncharacterised proteins. At the same time,
we must not forget those fundamental experimental skills needed to confirm the
predictions or send the analysts back to the drawing board to devise new ones.
PMID- 24358026
TI - The Importance of k-Space Trajectory on Off-Resonance Artifact in Segmented Echo
Planar Imaging.
AB - Segmented interleaved echo planar imaging (EPI) is a highly efficient data
acquisition technique; however, EPI is sensitive to artifacts from off-resonance
spins. The choice of k-space trajectories is important in determining how off
resonance spins contribute to image artifacts. Top-down and center-out
trajectories are theoretically analyzed, simulated, implemented, and tested in
phantom and volunteer experiments. Theoretical results show off-resonance
artifact manifests as a simple positional shift for the top-down trajectory,
while for the center-out trajectory off-resonance artifact manifests as a
splitting of the object, which entails both shift and blurring. These results
were validated using simulation and phantom scan data where a frequency-offset
was introduced ranging from -300 Hz to +300 Hz. As predicted by the theoretical
results, inferior image quality was observed for the center-out trajectory in a
single volunteer. Off-resonance produces more severe and complex artifacts with
the center-out trajectory than the top-down trajectory.
PMID- 24358028
TI - Financing essential HIV services: a new economic agenda.
PMID- 24358030
TI - Improving treatment of children with autism spectrum disorder in low- and middle
income countries: the role of non-specialist care providers.
PMID- 24358029
TI - Non-specialist psychosocial interventions for children and adolescents with
intellectual disability or lower-functioning autism spectrum disorders: a
systematic review.
AB - BACKGROUND: The development of effective treatments for use by non-specialists is
listed among the top research priorities for improving the lives of people with
mental illness worldwide. The purpose of this review is to appraise which
interventions for children with intellectual disabilities or lower-functioning
autism spectrum disorders delivered by non-specialist care providers in community
settings produce benefits when compared to either a no-treatment control group or
treatment-as-usual comparator. METHODS AND FINDINGS: We systematically searched
electronic databases through 24 June 2013 to locate prospective controlled
studies of psychosocial interventions delivered by non-specialist providers to
children with intellectual disabilities or lower-functioning autism spectrum
disorders. We screened 234 full papers, of which 34 articles describing 29
studies involving 1,305 participants were included. A majority of the studies
included children exclusively with a diagnosis of lower-functioning autism
spectrum disorders (15 of 29, 52%). Fifteen of twenty-nine studies (52%) were
randomized controlled trials and just under half of all effect sizes (29 of 59,
49%) were greater than 0.50, of which 18 (62%) were statistically significant.
For behavior analytic interventions, the best outcomes were shown for development
and daily skills; cognitive rehabilitation, training, and support interventions
were found to be most effective for improving developmental outcomes, and parent
training interventions to be most effective for improving developmental,
behavioral, and family outcomes. We also conducted additional subgroup analyses
using harvest plots. Limitations include the studies' potential for performance
bias and that few were conducted in lower- and middle-income countries.
CONCLUSIONS: The findings of this review support the delivery of psychosocial
interventions by non-specialist providers to children who have intellectual
disabilities or lower-functioning autism spectrum disorders. Given the scarcity
of specialists in many low-resource settings, including many lower- and middle
income countries, these findings may provide guidance for scale-up efforts for
improving outcomes for children with developmental disorders or lower-functioning
autism spectrum disorders. PROTOCOL REGISTRATION: PROSPERO CRD42012002641
PMID- 24358032
TI - Malaria and severe anemia: thinking beyond Plasmodium falciparum.
PMID- 24358031
TI - Major burden of severe anemia from non-falciparum malaria species in Southern
Papua: a hospital-based surveillance study.
AB - BACKGROUND: The burden of anemia attributable to non-falciparum malarias in
regions with Plasmodium co-endemicity is poorly documented. We compared the
hematological profile of patients with and without malaria in southern Papua,
Indonesia. METHODS AND FINDINGS: Clinical and laboratory data were linked for all
patients presenting to a referral hospital between April 2004 and December 2012.
Data were available on patient demographics, malaria diagnosis, hemoglobin
concentration, and clinical outcome, but other potential causes of anemia could
not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients
and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a
hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P.
malariae infection had the lowest hemoglobin concentration (n = 1,608, mean =
8.93 [95% CI 8.81-9.06]), followed by those with mixed species infections (n =
8,645, mean = 9.22 [95% CI 9.16-9.28]), P. falciparum (n = 37,554, mean = 9.47
[95% CI 9.44-9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49-9.57]); p
value for all comparisons <0.001. Severe anemia (hemoglobin <5 g/dl) was present
in 8,151 (3.7%) patients. Compared to patients without malaria, those with mixed
Plasmodium infection were at greatest risk of severe anemia (adjusted odds ratio
[AOR] 3.25 [95% CI 2.99-3.54]); AORs for severe anaemia associated with P.
falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00-2.23), 1.87 (95% CI
1.74-2.01), and 2.18 (95% CI 1.76-2.67), respectively, p<0.001. Overall, 12.2%
(95% CI 11.2%-13.3%) of severe anemia was attributable to non-falciparum
infections compared with 15.1% (95% CI 13.9%-16.3%) for P. falciparum
monoinfections. Patients with severe anemia had an increased risk of death (AOR =
5.80 [95% CI 5.17-6.50]; p<0.001). Not all patients had a hemoglobin measurement,
thus limitations of the study include the potential for selection bias, and
possible residual confounding in multivariable analyses. CONCLUSIONS: In Papua P.
vivax is the dominant cause of severe anemia in early infancy, mixed P. vivax/P.
falciparum infections are associated with a greater hematological impairment than
either species alone, and in adulthood P. malariae, although rare, is associated
with the lowest hemoglobin concentration. These findings highlight the public
health importance of integrated genus-wide malaria control strategies in areas of
Plasmodium co-endemicity.
PMID- 24358033
TI - Citrobacter Infection and Wnt signaling.
AB - Gut flora generally contributes to a healthy environment while both commensal and
pathogenic bacteria that influence the innate and adaptive immune responses, can
cause acute and/or chronic mucosal inflammation. Citrobacter rodentium (C.
rodentium) is a member of the family of enteropathogens that provide an excellent
in vivo model to investigate the host-pathogen interactions in real-time. It is
the etiologic agent for transmissible murine colonic hyperplasia (TMCH) while
inflammation following C. rodentium infection is dependent upon the genetic
background. Ongoing and completed studies in this model have so far established
that Wnt/beta-catenin, Notch and PI3K pathways regulate colonic crypt hyperplasia
while epithelial-stromal cross-talk, mediated by MEK/ERK/NF-kappaB signaling,
regulates inflammation and/or colitis in susceptible strains. The C. rodentium
induced hyperplastic state also increases the susceptibility to either mutagenic
insult or in mice heterozygous for Apc gene. The ability to modulate the host
response to C. rodentium infection therefore provides an opportunity to delineate
the mechanisms that determine mucosal hyperplasia, intestinal inflammation,
and/or neoplasia as disease outcomes.
PMID- 24358034
TI - A Review of Multiple Health Behavior Change Interventions for Primary Prevention.
AB - Most individuals engage in multiple unhealthy lifestyle behaviors with the
potential for negative health consequences. Yet most health promotion research
has addressed risk factors as categorically separate entities, and little is
known about how to effectively promote multiple health behavior change (MHBC).
This review summarizes the recent literature (January 2004 to December 2009) on
randomized clinical trials evaluating MHBC interventions for primary prevention.
Combining all the studies across all the reviews, fewer than 150 studies were
identified. This is a fraction of the number of trials conducted on changing
individual behavioral risks. Three primary behavioral clusters dominated: (1) the
energy balance behaviors of physical activity and diet; (2) addictive behaviors
like smoking and other drugs; and (3) disease-related behaviors, specifically
cardiovascular disease (CVD) and cancer related. Findings were largely
disappointing for studies of diet and physical activity, particularly with youth.
Treating 2 addictions, including smoking, resulted in greater long-term sobriety
from alcohol and illicit drugs. MHBC intervention effects were stronger and more
consistent for cancer prevention than CVD prevention. MHBC interventions offer a
new paradigm for broader, more comprehensive health promotion; however, the
potential value in maximizing intervention impact is largely unmet.
PMID- 24358035
TI - High-fiber rye diet increases ileal excretion of energy and macronutrients
compared with low-fiber wheat diet independent of meal frequency in ileostomy
subjects.
AB - BACKGROUND: Whole-grain foods and cereal dietary fiber intake is associated with
lower body weight. This may partly result from lower energy utilization of high
fiber diets. OBJECTIVE: In the present study, the impact on ileal excretion of
energy and macronutrients in response to a rye bread high-fiber diet compared to
a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal
frequency on apparent absorption of nutrients was studied for the first time.
DESIGN: Ten participants that had undergone ileostomy consumed standardized iso
caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2
weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks.
The diets were consumed in an ordinary (three meals per day) and a nibbling
(seven meals per day) meal frequency in a cross-over design. Ileal effluents were
collected during 24 h at the third day of each of the four dietary periods and
analyzed for gross energy and nutrient contents. RESULTS: The results showed that
intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet
caused an increase in ileal excretion of energy and macronutrients. The effect
was independent of meal frequency. This suggests that a high intake of rye may
result in lower availability of macronutrients for small intestinal digestion and
absorption. A regular intake of rye may therefore have implications for weight
management.
PMID- 24358036
TI - Adherence to the Nordic Nutrition Recommendations in a Nordic population with
metabolic syndrome: high salt consumption and low dietary fibre intake (The
SYSDIET study).
AB - BACKGROUND: The Nordic countries collaborate in setting recommendations for
intake of nutrients by publishing the Nordic Nutrition Recommendations (NNR).
Studies exploring how well the Nordic population adheres to the NNR are limited
and none are available for the metabolic syndrome (MetS) subgroup. Individuals
with MetS are a large part of the adult Nordic population and their diet's
nutritional quality is of great importance as it can affect the progression of
MetS. OBJECTIVE: To evaluate nutritional intake in a cohort of Nordic adults with
MetS or MetS risk factors and their adherence to the NNR. DESIGN: A multi-centre
study was carried out in six centres in four Nordic countries (SYSDIET CoE).
Participants (n=175) were 30-65 years of age, with BMI 27-38 kg/m(2) and had at
least two criteria for MetS. The NNR was used to evaluate the baseline nutrient
intake calculated from the participants' 4-day food diaries using national
nutrient databases. RESULTS: Less than 20% of participants consumed <=10 E% from
saturated fat as recommended in the NNR. Recommended intake (RI) of
polyunsaturated fat was met by approximately one-third of participants. Only 20%
of men and 26% of women met the RI of dietary fibre. Intake below the defined
lower intake level of 2.5 ug/day for vitamin D was observed in nearly 20% of
participants. The daily median intake of salt was 8.8 g for men and 6.7 g for
women. CONCLUSION: Dietary quality of this Nordic population with Mets or MetS
risk factors is unsatisfactory and characterised by high intakes of SFA and
sodium and low intakes of PUFA and dietary fibre. Vitamin D intake was below RI
level in a large part of the population. Authorities in the Nordic countries are
encouraged to develop intervention programmes for high-risk groups.
PMID- 24358037
TI - Comparison of estimated energy intake using Web-based Dietary Assessment Software
with accelerometer-determined energy expenditure in children.
AB - BACKGROUND: The OPUS (Optimal well-being, development and health for Danish
children through a healthy New Nordic Diet) project carried out a school meal
study to assess the impact of a New Nordic Diet (NND). The random controlled
trial involved 834 children aged 8-11 in nine local authority schools in Denmark.
Dietary assessment was carried out using a program known as WebDASC (Web-based
Dietary Assessment Software for Children) to collect data from the children.
OBJECTIVE: To compare the energy intake (EI) of schoolchildren aged 8-11
estimated using the WebDASC system against the total energy expenditure (TEE) as
derived from accelerometers worn by the children during the same period. A second
objective was to evaluate the WebDASC's usability. DESIGN: Eighty-one
schoolchildren took part in what was the pilot study for the OPUS project, and
they recorded their total diet using WebDASC and wore an accelerometer for two
periods of seven consecutive days: at baseline, when they ate their usual packed
lunches and at intervention when they were served the NND. EI was estimated using
WebDASC, and TEE was calculated from accelerometer-derived activity energy
expenditure, basal metabolic rate, and diet-induced thermogenesis. WebDASC's
usability was assessed using a questionnaire. Parents could help their children
record their diet and answer the questionnaire. RESULTS: Evaluated against TEE as
derived from the accelerometers worn at the same time, the WebDASC performed just
as well as other traditional methods of collecting dietary data and proved both
effective and acceptable with children aged 8-11, even with perhaps less familiar
foods of the NND. CONCLUSIONS: WebDASC is a useful method that provided a
reasonably accurate measure of EI at group level when compared to TEE derived
from accelerometer-determined physical activity in children. WebDASC will benefit
future research in this area.
PMID- 24358038
TI - Hepatitis C Virus NS5B Sequence-Based Genotyping Analysis of Patients From the
Sharkia Governorate, Egypt.
AB - BACKGROUND: Chronic hepatitis C virus infection and its sequela are major health
problems facing the Egyptian community. The high prevalence and spread rates of
the disease require serious actions to stop or decrease these rates.
Determination of HCV genotypes and subgenotypes adds significant knowledge about
the epidemiology of the disease, and provides an added value in the decision
making process of what strategy to follow and what therapy response to expect.
The molecular epidemiology and genetic variability of HCV variants circulating in
Egypt still need further analysis. OBJECTIVES: The study was held to evaluate the
genotype and subgenotype of the hepatitis c virus circulating in Sharkia as one
of the large governorates of Egypt, which was not included in any study for
genotyping of the virus before. PATIENTS AND METHODS: The HCV molecular
epidemiology in Sharkia governorate was studied using direct sequencing and
further phylogenetic analysis of a partial NS5B region of the HCV genome from 63
patients. HCV genotype and subtype were successfully determined in 62 out of 63
patients. RESULTS: The highest prevalent genotype was genotype 4a, which was
found in 57 patients (92%) followed by 2 isolates (3%) with genotype 4o, 2
strains (3%) with genotype 1g and one isolate (2%) with genotype 4n. CONCLUSIONS:
This molecular epidemiology study revealed high prevalence of HCV genotype 4,
subtype 4a among Egyptian patients residing in Sharkia governorate, Egypt.
PMID- 24358039
TI - Prevalence and risk factors of hepatitis C virus infection in amol city, north of
iran: a population-based study (2008-2011).
AB - BACKGROUND: Hepatitis C Virus (HCV) infection is one of the most important causes
of chronic liver disease and related problems in the world .There are few
population-based studies on the prevalence and risk factors of hepatitis C
infection in Iran, which could not provide enough information. Moreover, the
prevalence and risk factors of hepatitis C infection are not similar in all parts
of Iran. OBJECTIVES: The aim of this survey was to determine the prevalence and
risk factors of HCV infection in the general population of the city of Amol,
north of Iran. PATIENTS AND METHODS: This was a population-based study. Using a
cluster sampling approach, 6145 individuals of both genders and different ages
were involved from general population of urban and rural areas of Amol, The
inclusion criteria were Iranian nationality, willing to participate in the study,
and lifelong residence in Amol city and surrounding areas. Anti-hepatitis C
antibody was measured by a third generation of ELISA. The positive results were
confirmed by Recombinant Immuno Blot Assay (RIBA) and quantitative HCV-RNA
polymerase chain reaction (PCR) tests. Potential risk factors of HCV transmission
were recorded. RESULTS: The mean age of participants was 42.70 +/- 17.10 years.
Of these participants, 57.2% (n = 3483) were male. Anti-HCV antibody was positive
in 12 individuals from which five were RIBA positive. Three of these subjects
were PCR positive. The prevalence of HCV was more predominant among males than
females. The common risk factors among the study subjects included history of
minor or major surgery (34.7%), unsterile punctures (21.2%), history of
traditional phlebotomy (5.8%), and history of hepatitis among close relatives
(5.7%). In univariate regression analysis, unsterile punctures and history of
infection in family members were associated with HCV infection. CONCLUSIONS: We
confirm that in Amol city and surrounding areas, the prevalence of true HCV
infection is 0.05%, which is lower than that previously reported from Iran.
PMID- 24358040
TI - Clinical Profile and HLA Typing of Autoimmune Hepatitis From Pakistan.
AB - BACKGROUND: Human leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH)
has been investigated in different populations and ethnic groups, but no such
data is available from Pakistan. OBJECTIVES: The aim of this study was to
evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the
associated antigens and alleles by performing HLA typing. PATIENTS AND METHODS: A
total of 58 patients, diagnosed and treated as AIH in the last 10 years were
reviewed. Diagnosis was based on International AIH Group criteria. Forty one
patients underwent liver biopsy. HLA typing was performed in 44 patients and 912
controls by serological method for HLA A and B, and by PCR technique using
sequence specific primers for DR alleles. RESULTS: Of 58 cases, 35 were females
(60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10
22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the
remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients
(84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of
presentation. Among 41 patients who underwent liver biopsy, thirty-two had
advance stages III and IV disease, and twenty had severe grade of inflammation.
Fifteen patients had other associated autoimmune diseases and one developed
hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10
(25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40
(61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032)
and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical
significance than controls. CONCLUSIONS: AIH in our region presents with advanced
disease affecting predominantly children and adolescents. There is a genetic
association of HLA DR6 along with other alleles and antigens in our patients with
AIH.
PMID- 24358041
TI - Consensus interferon plus ribavirin for hepatitis C genotype 3 patients
previously treated with pegylated interferon plus ribavirin.
AB - BACKGROUND: Not enough data are available about the effectiveness of consensus
interferon (CIFN) among HCV genotype 3 patients who failed to respond to
pegylated interferon and ribavirin. OBJECTIVES: We aimed to assess the efficacy
and safety of CIFN and ribavirin in non-responders and relapsers to pegylated
interferon with ribavirin therapy. PATIENTS AND METHODS: This open-label
investigator-initiated study included 44 patients who received CIFN 15 ug /day
plus ribavirin 800-1200 mg daily. In patients with an early virological response
(EVR), the dose of CIFN was reduced to 15 ug thrice a week for further 36 weeks.
Patients with delayed virological response continued to receive daily CIFN plus
ribavirin to complete 48 weeks. The patients were considered "non-responders" if
there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV
RNA at 24 weeks. RESULTS: Twenty-four patients (55%) were non-responders and 20
patients were relapsers to the previous treatment with pegylated interferon plus
ribavirin (mean age 43.6 +/- 9.4 years, males 25 (57%)). Nine patients were
clinically cirrhotic (Child A). End of treatment virological response was
achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred
in 12 (27.3%). Out of these 12 patients, eight were non-responders and four were
relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosis was
associated with low SVR. Adverse events were fever, myalgia, anorexia,
depression, and weight loss. Two patients received granulocyte colony stimulating
factor for transient neutropenia. Seven patients were given erythropoietin to
improve hemoglobin, and six were treated for mild depression. Two patients
developed portosystemic encephalopathy. CONCLUSIONS: More than one-quarter of
treatment-experienced patients with HCV genotype 3 achieved SVR after re
treatment with consensus interferon plus ribavirin.
PMID- 24358042
TI - Type II Autoimmune Hepatitis and Small Duct Sclerosing Cholangitis in a Seven
Years Old Child: An Overlap Syndrome?
AB - INTRODUCTION: Autoimmune hepatitis is an inflammatory disease with multifactorial
ethiopatogenesis, characterized by lympho-monocytic infiltration of liver,
presence of serum autoantibodies (ANA, SMA, LKM-1) and high levels of
immunoglobulins. Overlap syndromes are defined as the association of autoimmune
hepatitis with cholestatic diseases such as primary biliary cirrhosis and primary
sclerosing cholangitis. The boundaries of these syndromes as distinct
pathological entities are still matter of debate and they could be part of a
major liver autoimmune disease. Furthermore, cholestatic diseases may present
even with atypical features (AMA-negative primary cirrohosis, primary sclerosing
cholangitis with normal cholangiography). CASE PRESENTATION: We herein describe a
case of a 7 year-old child affected by an overlap syndrome between type 2
autoimmune hepatitis and small duct primary sclerosing cholangitis. Although
characterized by a severe onset, the disease showed a good response to treatment
with prednisone and azathioprine. CONCLUSIONS: The association of type 2
autoimmune hepatitis and small duct primary cholangitis has been rarely reported
in literature and this report adds new data on this still unclear entity.
PMID- 24358043
TI - Amino Acid Polymorphisms Within the Entire HCV NS5A Region in Estonian Chronic
HCV 1b Patients With Different Treatment Response.
AB - BACKGROUND: A substantial proportion of hepatitis C virus (HCV)-1b infected
patients do not response to pegylated interferon-alpha plus ribavirin
(PegIFNalpha/RBV) combination therapy that was partially associated with
mutations in the non-structural 5A (NS5A) protein. OBJECTIVES: Analysis of NS5A
polymorphisms in HCV genotype 1b pre-treatment serum samples from Estonian
patients and their effect on the treatment response. PATIENTS AND METHODS: Twenty
nine complete NS5A sequences obtained from patients with chronic HCV-1b infection
who had received combined therapy with PegIFNalpha-2a/RBV were analyzed and
compared with the prototype strain HCV-J. Twelve patients achieved a sustained
virological response (SVR), 15 were non-SVR and 2 patients stopped treatment
because of side effects. RESULTS: No significant difference in total number of
amino acid mutations was observed between isolates from SVR and non-SVR patients
in any known regions of the NS5A protein. However, specific amino acid
substitutions at positions 1989 and 2283 correlated significantly with SVR,
mutations at positions 1979, 2107, 2171 and 2382 were associated with non
response to treatment and amino acid substitution at position 2319 was observed
in relapsers. At phylogenetic analysis, NS5A nucleotide sequences have been
subdivided into four groups characterized by the different treatment response.
Twenty-four novel nucleotide polymorphisms and 11 novel amino acid polymorphisms
were identified based on the phylogenetic tree topology. CONCLUSIONS: Specific
amino acid substitutions correlating with the treatment response were found.
Polymorphisms revealed by phylogenetic analysis may define the signature patterns
for treatment susceptible and treatment resistant strains prevalent in Estonia.
PMID- 24358044
TI - The effect of helicobacter pylori eradication on liver fat content in subjects
with non-alcoholic Fatty liver disease: a randomized open-label clinical trial.
AB - BACKGROUND: The role of Helicobacter pylori (HP) in the pathogenesis of
nonalcoholic fatty liver disease (NAFLD) is unclear. OBJECTIVES: The aim of this
study was to evaluate the effect of HP eradication on liver fat content (LFC),
liver function tests (LFT), lipid profile, and homeostasis model assessment-IR
(HOMA-IR) index in NAFLD. PATIENTS AND METHODS: Dyspeptic patients with increased
serum aminotransferase levels were enrolled in the study. The exclusion criteria
were factors affecting serum aminotransferase or HP treatment strategy.
Participants with persistent elevated serum aminotransferase level and ultrasound
criteria for identification of fatty liver were presumed to have NAFLD. "NAFLD
liver fat score" was used to classify NAFLD. Those with "NAFLD liver fat score"
greater than -0.64 and positive results for urea breath test (UBT), were
included. Lifestyle modification was provided to all participants. HP eradication
was performed in intervention arm. LFC, fasting serum glucose (FSG), alanine
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), triglyceride (TG), cholesterol (CHOL), high and low-density lipoprotein
(HDL, LDL), and HOMA-IR were checked at baseline and after that, at intervals of
eight weeks and twenty four weeks. RESULTS: One hundred (49 males) patients with
the mean age of 43.46 (+/- 11.52) were studied. Repeated measure ANOVA showed a
significant reduction in LFC, anthropometric measurements, and laboratory
parameters (except for HDL) in the both groups during the study; however, no
significant difference was observed between the groups. CONCLUSIONS: It seems
that HP eradication per se might not affect LFC, LFT, lipid profile, and insulin
resistance in dyspeptic NAFLD patients.
PMID- 24358046
TI - Sofosbuvir has come out of the magic box.
PMID- 24358045
TI - How Much Weight Loss is Effective on Nonalcoholic Fatty Liver Disease?
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver
disease worldwide with no specific treatment. Weight loss is the most effective
therapeutic strategy in its management; however, there is no consensus on its
specifics. Thus, this study was conducted to evaluate the effects of weight loss
on liver enzymes, markers of inflammation, oxidative stress and CK18-M30
(cytokeratin 18) as a biomarker of hepatocellular apoptosis. OBJECTIVES: To study
the effect of weight reduction diet as an exclusive treatment for NAFLD. PATIENTS
AND METHODS: Forty four patients with NAFLD received a diet including a 500 to
1000 kcal per day intake reduction as30% fat, 15% protein, and 55% carbohydrate
for six months. Anthropometric parameters, alanine aminotransferase (ALT),
aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lipid
profile, malondialdehyde (MDA), TNF-alpha, IL-6, CK18-M30 were measured at
baseline and at the end of the study. At the end of follow up, patients were
classified as adherent or nonadherent to treatment according to a weight loss of
>= 5%, or < 5% of initial body weight, respectively. RESULTS: Twenty five
patients were classified as adherent group and nineteen as nonadherent group
(9.7% vs. 1.9% total body weight loss after 6 months, respectively). After 6
months, changes in adherent and nonadherent groups were as follows: reduction in
body weight from 93.7 +/- 15.8 kg to 84.2 +/- 13.4 kg vs. 94 +/- 16.6 kg to 92.2
+/- 16.2 kg (P < 0.05), BMI from 32.7 +/- 3.9 to 29.5 +/- 3.2 vs.31.8 +/- 5.4 to
31.1 +/- 5.3 (P < 0.001), and waist circumference from 105.1 +/- 12.6 cm to 97.4
+/- 9.8 cm vs.106.8 +/- 14.2 cm to 103.7 +/- 14 cm (P < 0.001), respectively.
Diastolic blood pressure was significantly decreased in adherent group (from 80.2
+/- 5.1 mmHg to 76.9 +/- 5 mmHg; P < 0.001). Also, total cholesterol, LDL,
triglyceride, ALT, AST, GGT and CK18-M30 levels were significantly decreased in
the adherent group compared to nonadherent group (P < 0.05). CONCLUSIONS: This
intervention offers a practical approach for treatment of patients with NAFLD
with diet therapy.
PMID- 24358047
TI - Can genetic information change patient behavior to reduce Type 2 diabetes risk?
PMID- 24358048
TI - Deformation of a Two-domain Lipid Bilayer due to Asymmetric Insertion of Lipid
modified Ras Peptides.
AB - Ras proteins are attached to the inner leaflet of the plasma membrane via a lipid
modified anchor. Membrane-bound Ras proteins laterally segregate into nanoscale
signaling platforms called nanoclusters. It has been shown that the membrane
domain preference of Ras nanoclusters varies with the nature of lipidation but
their effect on the membrane has not been well understood. To investigate the
effect of Ras insertion on membrane structure, we carried out numerous coarse
grained molecular dynamics (CGMD) simulations on a two-domain
DPPC/DLiPC/cholesterol lipid bilayer in which different number and type of H-ras
peptides were attached on one side. We have shown previously that this lipid
mixture forms co-existing liquid-ordered/liquid-disordered (L o /L d ) domains
and that different H-ras peptides form clusters that variously accumulate at the
L o /L d regions or the boundary between them. Here we show that asymmetric
insertion of each of these peptides induces a vertical relative displacement of
the domains and deforms the bilayer, with the domain boundary serving as the
center of deformation. The extent of the deformation, however, varies with the
type and number of lipid modification. This is because the number and type of the
Ras lipid tails determines the degree to which the stress caused by asymmetric
peptide insertion is relieved by inter-leaflet cholesterol transfer and lipid
tilt. In addition, we have characterized the mechanism of bilayer deformation
based on the collective effect of the Ras peptides on inter-leaflet surface area,
pressure profile and line tension differences. This allowed us to elucidate how
Ras lipid modification affects membrane geometry and how a two-domain bilayer
adjusts its shape through boundary deformation. The result contributes to a
better understanding of Ras signaling platforms and highlights some of the
mechanisms by which a multi-domain membrane responds to external perturbation.
PMID- 24358050
TI - Flexible Assertive Community Treatment, Severity of Symptoms and Psychiatric
Health Service Use, a Real life Observational Study.
AB - BACKGROUND: Introduction of Flexible Assertive Community Treatment (FACT) may be
associated with increased remission rates and changes in patterns of care. The
present paper reports on differences in psychosocial functioning and health care
use between patients in FACT and two groups of patients not currently provided
with a specific model of community service. METHODS: The ongoing "Pharmacotherapy
Monitoring and Outcome Survey" provided routine outcome measures of patients
using antipsychotics in the north of the Netherlands. Level of psychosocial
functioning was assessed using the Health of the Nations Outcome Scales (HoNOS)
and matched with psychiatric health care consumption obtained from the
Psychiatric Case Register. Patients who never received FACT, patients ever in
FACT but not at assessment date, and patients in FACT were identified. Data were
subjected to multilevel linear regression analysis. RESULTS: Data showed that
most patients in FACT also had non-FACT episodes after the start of FACT.
Furthermore, patients in FACT displayed higher levels of psychosocial functioning
and used more outpatient care than the other two groups. CONCLUSIONS: Patients in
FACT receive more outpatient care and have better psychosocial functioning.
However, causal inferences cannot be derived from these data. In addition,
membership of a FACT-team in this setting did not last indefinitely.
PMID- 24358049
TI - Changes in Cortical Activity During Real and Imagined Movements: an ERP Study.
AB - This study aims to compare the topographic distribution of cortical activation
between real and imagined movement through event-related potential (ERP). We are
specifically interested in identifying, the topographic distribution of activated
areas, the intensity of activated areas, and the temporal occurrence of these
activations on preparation and motor response phases. Twelve healthy and right
handed subjects were instructed to perform a task under real and imagery
conditions. The task was performed simultaneously to electroencephalographic
(EEG) recording. When compared the conditions, we found a statistically
significant difference in favor of real condition revealed by performing an
unpaired t-test with multiple corrections of Bonferroni, demonstrating negative
activity on electrode C3 and positive activity on the electrode C4 only in motor
response phase. These findings revealed similar functional connections
established during real and imagery conditions, suggesting that there are common
neural substrate and similar properties of functional integration shared by
conditions.
PMID- 24358051
TI - Proposals for Mental Health in Italy at the End of the Nineteenth Century:
between Utopia and Anticipating the "Basaglia Law".
AB - The present work refers to the debate which took place in Italy in the final
years of the nineteenth century in relation to mental health and lunatic asylums,
from which emerged various innovative proposals for avoiding compulsory
confinement in numerous cases. Some of them became part of new legislative
regulations regarding asylums, but most were excluded. Today, a new historical
interpretation allows us to grasp a connection between Law 180, dated 1978 and
known as the "Basaglia Law" from the name of its promoter, and alternative
proposals to asylum custody omitted from the 1904 law.
PMID- 24358052
TI - The role of positive emotion and contributions of positive psychology in
depression treatment: systematic review.
AB - The present study aims to conduct a systematic review of the literature by
checking the impact of positive emotion in the treatment of depression and on the
use of strategies of positive psychology which involves positive emotion to treat
and reduce symptoms of depression. For this purpose, we conducted searches in
databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400
studies. After inclusion application and exclusion criteria, 28 articles
remained, presented and discussed in this study. The studies have important
relations between humor and positive emotion as well as a significant improvement
in signs and symptoms of depression using differents strategies of positive
psychology. Another relevant aspect is the preventative character of the proposed
interventions by positive psychology by the fact that increase well-being and
produce elements such as resilience and coping resources that reduce the
recurrent relapses in the treatment of depression. The strategies of positive
psychology, such as increasing positive emotions, develop personal strengths:
seeking direction, meaning and engagement for the day-to-day life of the
patients, appear as potentially tools for the prophylaxis and treatment of
depression, helping to reduce signs and symptoms as well as for prevention of
relapses.
PMID- 24358053
TI - Cognitive behavioral therapy for young people after l'aquila earthquake.
AB - OBJECTIVE: Cognitive behavior therapy (CBT) emerges as the best validated
therapeutic approach for children and adolescents who experienced trauma-related
symptoms, particularly associated with anxiety or mood disorders. The aim of this
study was to evaluate the CBT efficacy among young people exposed to L'Aquila
earthquake, in 2009. METHODS: one year after the disaster, 39 young subjects as a
case group (CBT treated) and 24 as a comparison group (no CBT treated) were
evaluated with the Impact of Event Scale Revised (IES-R), the General Health
Questionnaire-12 items (GHQ-12) and the Brief Cope. CBT was conducted in 12
sessions (once per week for 3 months). After CBT intervention, both groups were
evaluated again with the same psychometric instruments. RESULTS: our results show
a significantly decrease in post traumatic symptoms and psychological distress
severity in CBT group. It was attributable to an improvement in each of three
PTSD dimensions (intrusion, avoidance, and arousal) and in the total score of IES
R (p< 0.04). Among CBT treated group, subjects that adopted "planning/problem
solving" coping strategies (p < .02) and "religiosity" (p < .045) show higher
improvement in psychological distress. CONCLUSIONS: our findings show the
efficacy of CBT and the influence of individual coping strategies in the
improvement of posttraumatic stress symptoms and psychological distress among
young people seeking help from an outpatients service for young people with
psychiatric problems (the SMILE) after the catastrophic disaster in L'Aquila.
PMID- 24358054
TI - Wide-field optical detection of nanoparticles using on-chip microscopy and self
assembled nanolenses.
AB - The direct observation of nanoscale objects is a challenging task for optical
microscopy because the scattering from an individual nanoparticle is typically
weak at optical wavelengths. Electron microscopy therefore remains one of the
gold standard visualization methods for nanoparticles, despite its high cost,
limited throughput and restricted field-of-view. Here, we describe a high
throughput, on-chip detection scheme that uses biocompatible wetting films to
self-assemble aspheric liquid nanolenses around individual nanoparticles to
enhance the contrast between the scattered and background light. We model the
effect of the nanolens as a spatial phase mask centred on the particle and show
that the holographic diffraction pattern of this effective phase mask allows
detection of sub-100 nm particles across a large field-of-view of >20 mm2. As a
proof-of-concept demonstration, we report on-chip detection of individual
polystyrene nanoparticles, adenoviruses and influenza A (H1N1) viral particles.
PMID- 24358055
TI - Effect of font size, italics, and colour count on web usability.
AB - Web usability measures the ease of use of a website. This study attempts to find
the effect of three factors - font size, italics, and colour count - on web
usability. The study was performed using a set of tasks and developing a survey
questionnaire. We performed the study using a set of human subjects, selected
from the undergraduate students taking courses in psychology. The data computed
from the tasks and survey questionnaire were statistically analysed to find if
there was any effect of font size, italics, and colour count on the three web
usability dimensions. We found that for the student population considered, there
was no significant effect of font size on usability. However, the manipulation of
italics and colour count did influence some aspects of usability. The subjects
performed better for pages with no italics and high italics compared to moderate
italics. The subjects rated the pages that contained only one colour higher than
the web pages with four or six colours. This research will help web developers
better understand the effect of font size, italics, and colour count on web
usability in general, and for young adults, in particular.
PMID- 24358057
TI - A Multi-Core Parallelization Strategy for Statistical Significance Testing in
Learning Classifier Systems.
AB - Permutation-based statistics for evaluating the significance of class prediction,
predictive attributes, and patterns of association have only appeared within the
learning classifier system (LCS) literature since 2012. While still not widely
utilized by the LCS research community, formal evaluations of test statistic
confidence are imperative to large and complex real world applications such as
genetic epidemiology where it is standard practice to quantify the likelihood
that a seemingly meaningful statistic could have been obtained purely by chance.
LCS algorithms are relatively computationally expensive on their own. The
compounding requirements for generating permutation-based statistics may be a
limiting factor for some researchers interested in applying LCS algorithms to
real world problems. Technology has made LCS parallelization strategies more
accessible and thus more popular in recent years. In the present study we examine
the benefits of externally parallelizing a series of independent LCS runs such
that permutation testing with cross validation becomes more feasible to complete
on a single multi-core workstation. We test our python implementation of this
strategy in the context of a simulated complex genetic epidemiological data
mining problem. Our evaluations indicate that as long as the number of concurrent
processes does not exceed the number of CPU cores, the speedup achieved is
approximately linear.
PMID- 24358058
TI - Design, Synthesis and Biological Evaluation of N4-Sulfonamido-Succinamic,
Phthalamic, Acrylic and Benzoyl Acetic Acid Derivatives as Potential DPP IV
Inhibitors.
AB - As incidence rate of type II diabetes mellitus continues to rise, there is a
growing need to identify novel therapeutic agents with improved efficacy and
reduced side effects. Dipeptidyl peptidase IV (DPP IV) is a multifunctional
protein involved in many physiological processes. It deactivates the natural
hypoglycemic incretin hormone effect. Inhibition of this enzyme increases
endogenous incretin level, incretin activity and should restore glucose
homeostasis in type II diabetic patients making it an attractive target for the
development of new antidiabetic drugs. One of the interesting reported anti- DPP
IV hits is Gemifloxacin which is used as a lead compound for the development of
new DPP IV inhibitors. In the current work, design and synthesis of a series of
N4-sulfonamido-succinamic, phthalamic, acrylic and benzoyl acetic acid
derivatives was carried out. The synthesized compounds were evaluated for their
in vitro anti-DPP IV activity. Some of them have shown reasonable bioactivity,
where the most active one 17 was found to have an IC50 of 33.5 MUM.
PMID- 24358056
TI - Coherent fiber supercontinuum for biophotonics.
AB - Biophotonics and nonlinear fiber optics have traditionally been two independent
fields. Since the discovery of fiber-based supercontinuum generation in 1999,
biophotonics applications employing incoherent light have experienced a large
impact from nonlinear fiber optics, primarily because of the access to a wide
range of wavelengths and a uniform spatial profile afforded by fiber
supercontinuum. However, biophotonics applications employing coherent light have
not benefited from the most well-known techniques of supercontinuum generation
for reasons such as poor coherence (or high noise), insufficient controllability,
and inadequate portability. Fortunately, a few key techniques involving nonlinear
fiber optics and femtosecond laser development have emerged to overcome these
critical limitations. Despite their relative independence, these techniques are
the focus of this review, because they can be integrated into a low-cost portable
biophotonics source platform. This platform can be shared across many different
areas of research in biophotonics, enabling new applications such as point-of
care coherent optical biomedical imaging.
PMID- 24358059
TI - Electrical Stimulation of NIH-3T3 Cells with Platinum-PEDOT-Electrodes Integrated
in a Bioreactor.
AB - The objective of this work involves the development and integration of electrodes
for the electrical stimulation of cells within a bioreactor. Electrodes need to
fit properties such as biocompatibility, large reversible charge transfer and
high flexibility in view of their future application as implants on the tympanic
membrane. Flexible thin-film platinum-poly(3,4-ethylene-dioxythiophene)
electrodes on a poly(ethylene terephthalate)-foil manufactured using microsystems
technology were integrated into a bioreactor based on the design of a 24 well
plate. The murine fibroblast cell line NIH-3T3 was cultured on the foil
electrodes and the cells were stimulated with direct voltage and unipolar pulsed
voltage. The amplitude, the pulse length and the ratio of pulse to pause were
varied. The stimulated cells were stained in order to determine the angle between
the cell cleavage plane of the dividing cells and the vector of the electric
field. These angles were subsequently used to calculate the polarization index,
which is a measure of the orientation of the metaphase plane of dividing cells
that occurs for example during wound healing or embryonic morphogenesis.
PMID- 24358060
TI - Preoperative digital carotid compression as a predictor of the need for shunting
during carotid endarterectomy.
AB - This study prospectively attempted to assess the need for shunting by
preoperative digital compression of the proximal common carotid artery and
correlated these findings with intraoperative assessment while performing carotid
endarterectomy under local anaesthesia. Preoperative digital compression is
highly predictive of the need for shunting intra-operatively and can be used as a
valuable test in carefully chosen patients. This may help in decreasing the need
for advanced neurological monitoring during carotid endarterectomy.
PMID- 24358061
TI - The Effects of Aging on Indices of Oxidative Stress and Apoptosis in the Female
Fischer 344/Nnia X Brown Norway/BiNia Rat Heart.
AB - Oxidative-nitrosative stress may play a role in age-associated cardiovascular
disease as implied by recent studies.However, limited research has been conducted
using aged female rodent models. In this study, we examined hearts obtained from
6-, 26-, and 30-month old female Fischer 344/Nnia x Brown Norway/BiNia (F344xBN)
rats in order to examine how aging affects levels of cardiac oxidative
nitrosative stress and apoptosis. Oxidative (superoxide anion and 4-HNE) and
nitrosative (protein nitrosylation) stress markers were increased 180 +/- 17 %,
110 +/- 3 %, and 14 +/- 2 %, respectively in 30-month hearts compared to the
hearts of 6-month female rats. Coincident with these changes in oxidative
nitrosative stress, aging was also found to be associated with increases in the
number of Tdt-mediated dUTP nick labeling (TUNEL)-positive cardiomyocytes,
alterations in the Bax/Bcl-2 ratio, and elevated cleavage of caspase-3.
Regression analysis demonstrates significant correlation in the age-associated
changes markers of oxidative-nitrosative stress with changes in apoptotic
signaling. The findings from this descriptive study imply that age-associated
increases in mitochondrial-mediated apoptosis may be associated with the increase
in oxidative-nitrosative stress in the aging F344xBN female heart.
PMID- 24358062
TI - Incidence and pattern of thyroid dysfunction in patients on chronic amiodarone
therapy: experience at a tertiary care centre in oman.
AB - OBJECTIVE: To determine the incidence and pattern of thyroid dysfunction (TD) in
patients on chronic amiodarone therapy. METHODS: A retrospective study which
evaluated 59 patients who had received amiodarone therapy regularly for at least
12 months from a period of 3 years from October 2007 to October 2010. The
patients were followed-up at the cardiac clinic at Sultan Qaboos University
Hospital, Muscat, Oman. RESULTS: The mean age of the cohort was 63 +/- 13 years
ranging from 27 to 98 years. Fifty-one percent (n = 30) of the patients were
female. There were 11 (19%) cases of thyroid dysfunction (TD). Seven (12%)
patients were hypothyroid, 3 (5%) had hyperthyroidism and 1 (2%) patient had sub
clinical hypothyroidism; no cases of sub-clinical hyperthyroidism were noted.
Female gender and presence of anti-thyroid peroxidase antibodies were
significantly associated with amiodarone-induced hypothyroidism (p = 0.001) while
age, amiodarone dose and duration of therapy were not correlated with the
development of TD (all p-values > 0.05). CONCLUSION: Amiodarone-induced thyroid
dysfunction is prevalent. Hypothyroidism was more frequent and seen more in
female patients and those who had positive anti-thyroid peroxidase antibodies.
Initial screening and periodic monitoring of thyroid function is mandatory for
all patients on amiodarone therapy.
PMID- 24358063
TI - Low bone mass is a risk factor in periodontal disease-related tooth loss in
patients with intellectual disability.
AB - Teeth are fundamental to maintaining good quality of life, but are often lost
prematurely in individuals with intellectual disability. Furthermore, since bone
mass decreases in menopausal women, women with intellectual disability have an
augmented risk of losing their teeth. However, the relationship between
periodontal disease-related tooth loss and bone mass has never been studied
specifically in patients with intellectual disability. This study evaluated this
relationship in a retrospective cohort study. Participants were female dental
patients aged between 20 and 50 years and with an intellectual disability, who
were treated in the Special Needs Dentistry unit of the Okayama University
Hospital from January 2009 to March 2010. Logistic regression analysis was used
to analyze which factors affect periodontal disease-related tooth loss.
Information relating to 12 predictor variables, including age and bone mass
level, was derived from medical records. The 27 subjects had a total of 704 teeth
at the time of initial examination, but 20 teeth (2.8%) had been lost owing to
periodontal disease by the time bone mass measurements were recorded. Results of
the multinomial logistic regression analysis indicated a significant odds ratio
for three items: number of missing teeth at the time of initial examination, bone
mass, and living environment. This result suggests that low bone mass is an
independent risk factor in tooth loss secondary to periodontal disease in
patients with intellectual disability. Dentists should thus take account of this
heightened risk of tooth loss when caring for post-menopausal women with
intellectual disability.
PMID- 24358065
TI - Application of MALDI-TOF MS for the Identification of Food Borne Bacteria.
AB - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
(MALDI-TOF MS) has recently emerged as a powerful tool for the routine
identification of clinical isolates. MALDI-TOF MS based identification of
bacteria has been shown to be more rapid, accurate and cost-efficient than
conventional phenotypic techniques or molecular methods. Rapid and reliable
identification of food-associated bacteria is also of crucial importance for food
processing and product quality. This review is concerned with the applicability
of MALDI-TOF MS for routine identification of foodborne bacteria taking the
specific requirements of food microbiological laboratories and the food industry
into account. The current state of knowledge including recent findings and new
approaches are discussed.
PMID- 24358064
TI - Influence of different post-core systems on impact stress: a pilot study.
AB - This pilot study compared impact strain at the core and root surfaces between two
different post-core systems. MATERIALS AND METHODS: The form of a bovine
mandibular front tooth was modified to resemble that of a human maxillary incisor
as a test specimen. A cast post and core (Metal PC) and composite resin and glass
fiber-reinforced epoxy resin post (Fiber-Resin PC) system were tested. Four
gauges were affixed to the buccal and lingual surfaces of the core and root. The
specimens were then embedded in a metal mold using dental stone. A pendulum-type
device with a pyramid-shaped metal impact object with a titanium alloy head was
used to provide 2 different shock forces. Maximum distortion was measured and
analyzed. RESULTS: Distortion at the core at each measurement point and total
amount of distortion with Fiber-Resin PC was significantly greater (p<0.05) than
that with Metal PC against both impact forces. On the other hand, distortion at
the root at the buccal measurement point with Fiber-Resin PC was significantly
less than that with Metal PC against both impact forces. Total distortion was
significantly less with Fiber-Resin PC than that with Metal PC against the
greater impact shock. Acceleration with Fiber-Resin PC was significantly less
than that with Metal PC against both impact forces. CONCLUSION: Fiber-Resin PC
has the potential to protect remaining root against traumatic force. This
suggests that a Fiber-Resin PC is more suitable for non-vital teeth against not
only occlusal but also traumatic impact force.
PMID- 24358066
TI - The Study of Genetic Relationship Among Third Generation Cephalosporin-resistant
Salmonella enterica Strains by ERIC-PCR.
AB - BACKGROUND AND OBJECTIVES: Salmonella is an important food-borne pathogen
responsible for disease in humans and animals. The aim of this study was to
investigate the genetic relationship among third generation cephalosporin
resistant Salmonella enterica strains by Enterobacterial Repetitive Intergenic
Consensus (ERIC)-PCR. METHODS: The study included all Salmonella isolates
obtained from clinical cases in a pediatric hospital in Tehran, Iran during 2006
to 2009. Antimicrobial susceptibility testing was performed according to the
Clinical and Laboratory Standards Institute. The genetic relationship between
third generation cephalosporins-resistant Salmonella enterica strains was
determined using ERIC-PCR. RESULTS: Of 136 Salmonella enterica isolates recovered
from pediatric patients, six isolates including four Salmonella enterica serotype
Infantis and two Salmonella enterica serotype Enteritidis showed an extended
spectrum cephalosporins resistant phenotype. ERIC-PCR differentiated Salmonella
enterica serotypes Infantis and Enteritidis into 2 distinct clusters arbitrarily
named as E1 and E2. Profile E1 was found in two Salmonella enterica serotype
Enteritidis isolates, and profile E2 was found in four Salmonella enterica
serotype Infantis isolates. CONCLUSION: Extended-spectrum cephalosporins
resistant Salmonella could be attributed to a few predominant serotypes including
Enteritidis and Infantis in this study. Genetic analysis using ERIC-PCR showed
that closely related clones are responsible for the occurrence of extended
spectrum cephalosporins resistant Salmonella infection in Tehran.
PMID- 24358067
TI - Celecoxib and Diclofenac Plus Omeprazole are Similarly Effective in the Treatment
of Arthritis in Patients at High GI Risk in the CONDOR Trial.
AB - OBJECTIVE: Compare effectiveness of celecoxib versus diclofenac plus omeprazole
in improving arthritis signs and symptoms in patients at high gastrointestinal
(GI) risk who were enrolled in the CONDOR (Celecoxib vs Omeprazole and Diclofenac
in Patients With Osteoarthritis and Rheumatoid Arthritis) trial. METHODS: CONDOR
was a 6-month, prospective, double-blind, triple-dummy, parallel-group,
randomized, multicenter trial comparing celecoxib 200 mg twice daily versus
diclofenac slow release (SR) 75 mg twice daily plus omeprazole 20 mg daily.
Patients were Helicobacter pylori negative, had osteoarthritis (OA) or rheumatoid
arthritis (RA), were aged >=60 years, were with or without a history of
gastroduodenal ulceration, or were >=18 years with previous gastroduodenal
ulceration. Patients' Global Assessment of Arthritis was determined at each study
visit. RESULTS: A total of 4484 patients were randomized to treatment (2238
celecoxib, 2246 diclofenac SR) and included in the intention-to-treat analyses.
Least squares mean (LSM) (standard error [SE]) for Patients' Global Assessment of
Arthritis was 3.219 (0.017) and 3.221 (0.017) at baseline for celecoxib and
diclofenac SR (p=0.90). Improvement in both groups was similar in months 2, 4,
and 6; at month 1 the LSM (SE) was 2.647 (0.017) and 2.586 (0.017) for celecoxib
and diclofenac (p=0.0025). LSM difference (SE) from baseline to final visit
demonstrated an improvement of 0.75 (0.02) in celecoxib-treated patients and 0.77
(0.02) in diclofenac SR-treated patients (p=0.42). CONCLUSIONS: Celecoxib and
diclofenac plus omeprazole were shown to have similar efficacy in patients with
OA and/or RA at increased GI risk who were enrolled in the CONDOR trial. TRIAL
REGISTRY: Trial was registered under ClinicalTrials.gov identifier NCT00141102.
PMID- 24358068
TI - Concomitance of IgM and IgG anti-dsDNA Antibodies Does Not Appear to Associate to
Active Lupus Nephritis.
AB - Previous reports proposed that the IgM anti-dsDNA antibody is protective for
lupus nephritis. In this cross-sectional study, we aimed to compare clinical
features of systemic lupus erythematosus (SLE) patients positive for IgG anti
dsDNA alone with those presenting both IgG and IgM anti-dsDNA. Anti-dsDNA
antibodies, urinary examination and complement levels were assessed in the day of
appointment. IgG and IgM anti-dsDNA antibodies were detected by indirect
immunofluorescence. Fifty-eight SLE patients (93.1% female, 81% European-derived,
mean age 42.8+/-14.7 years, mean duration of disease 10.9+/-8 years) positive for
IgG anti-dsDNA entered the study. Of those, 15 were also positive for the IgM
anti-dsDNA isotype. The group with both isotypes showed significant less
frequency of active nephritis (sediment changes and proteinuria) when compared to
patients with IgG anti-dsDNA alone (6.7% versus 34.9%, p=0.046). These data
suggest a nephroprotective role for IgM anti-dsDNA and a distinct biologic
behavior for this isotype in SLE.
PMID- 24358069
TI - The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in
Rheumatoid Arthritis: Data from BARFOT, a Multi-Centre Study of Early RA.
AB - BACKGROUND: There have been no reports on the effect of immigrant status and
socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. METHODS:
Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early
RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment
Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR)
response criteria were registered. In 2010, 1,430 patients completed a
questionnaire enquiring about demographics and lifestyle factors. RESULTS: One
hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline
immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28
(5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000),
VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs
8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ,
for up to 8 years of follow-up). Immigrant status did not have any effect on
swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did
not have any effect on treatment or outcome. CONCLUSIONS: Immigrants scored worse
in pain, function and TJC for up to 2 years of follow-up, but they did not differ
from non-immigrants in objective measures of inflammation or EULAR outcome. This
could be due to different perceptions of health and pain and/or the stress of
immigration. Socioeconomic class had no effect on treatment or outcome, and this
could be due to the relatively egalitarian society in Sweden.
PMID- 24358070
TI - The Pathophysiology of Primary Hip Osteoarthritis may Originate from Bone
Alterations.
AB - OBJECTIVES: The aim of this study was to investigate whether bone alterations
detected by hip magnetic resonance imaging (MRI) were associated with subsequent
primary hip OA. METHODS: We enrolled 7 patients with hip joint pain from their
first visit, at which hip joints were classified as grade 0 or I on the Kellgren
Lawrence grading scale. Plain radiographs and magnetic resonance imaging (MRI)
were performed on all cases, and pain was assessed with the Denis pain scale.
Average age, height, weight, body mass index, bone mineral density (L1-4),
central edge angle, Sharp's angle, and acetabular hip index were calculated.
RESULTS: Within two months of the onset of pain, 4 of the 7 cases showed broad
bone signal changes, while 3 cases showed local signal changes in the proximal
femur on hip MRI. Three to 6 months after the onset of pain, in all patients
whose pain was much improved, plain radiographs showed progression to further
stage OA. CONCLUSION: Our findings suggest that bone abnormalities in the
proximal femur might be involved in the pathogenesis of primary hip OA.
PMID- 24358071
TI - The Gold Nanorod-Biology Interface: From Proteins to Cells to Tissue.
AB - Gold nanorods absorb and scatter light strongly in the near-infrared portion of
the electromagnetic spectrum, making them ideal tissue contrast agents for
imaging techniques such as optical coherence tomography (OCT). Strong
interactions occur at the nano-bio interface, such as proteins binding to gold
nanorods forming a 'corona.' To fulfill the promise of nanorods for applications
such as contrast agents, we must better understand the intrinsic interactions of
these nanomaterials with biological systems at the molecular, cellular and tissue
level. In this paper, we briefly review the nanorod-protein interface. We then
present some new fast relaxation imaging (FReI) measurements of how the presence
of strongly-absorbing gold nanorods affects protein binding and folding, taking
into account inner filter effects and the strong quenching effect of nanorods on
fluorescent-labeled proteins. Next we show that two-photon photoluminescence of
the gold nanorods can be used to image the nanorods in tissue constructs,
allowing us to independently study their tissue distribution so they can be used
successfully as contrast agents in optical coherence microscopy.
PMID- 24358072
TI - Nonparametric Bayesian models through probit stick-breaking processes.
AB - We describe a novel class of Bayesian nonparametric priors based on stick
breaking constructions where the weights of the process are constructed as probit
transformations of normal random variables. We show that these priors are
extremely flexible, allowing us to generate a great variety of models while
preserving computational simplicity. Particular emphasis is placed on the
construction of rich temporal and spatial processes, which are applied to two
problems in finance and ecology.
PMID- 24358073
TI - Multiple-Shrinkage Multinomial Probit Models with Applications to Simulating
Geographies in Public Use Data.
AB - Multinomial outcomes with many levels can be challenging to model. Information
typically accrues slowly with increasing sample size, yet the parameter space
expands rapidly with additional covariates. Shrinking all regression parameters
towards zero, as often done in models of continuous or binary response variables,
is unsatisfactory, since setting parameters equal to zero in multinomial models
does not necessarily imply "no effect." We propose an approach to modeling
multinomial outcomes with many levels based on a Bayesian multinomial probit
(MNP) model and a multiple shrinkage prior distribution for the regression
parameters. The prior distribution encourages the MNP regression parameters to
shrink toward a number of learned locations, thereby substantially reducing the
dimension of the parameter space. Using simulated data, we compare the predictive
performance of this model against two other recently-proposed methods for big
multinomial models. The results suggest that the fully Bayesian, multiple
shrinkage approach can outperform these other methods. We apply the multiple
shrinkage MNP to simulating replacement values for areal identifiers, e.g.,
census tract indicators, in order to protect data confidentiality in public use
datasets.
PMID- 24358074
TI - Maximum Likelihood Estimation Over Directed Acyclic Gaussian Graphs.
AB - Estimation of multiple directed graphs becomes challenging in the presence of
inhomogeneous data, where directed acyclic graphs (DAGs) are used to represent
causal relations among random variables. To infer causal relations among
variables, we estimate multiple DAGs given a known ordering in Gaussian graphical
models. In particular, we propose a constrained maximum likelihood method with
nonconvex constraints over elements and element-wise differences of adjacency
matrices, for identifying the sparseness structure as well as detecting
structural changes over adjacency matrices of the graphs. Computationally, we
develop an efficient algorithm based on augmented Lagrange multipliers, the
difference convex method, and a novel fast algorithm for solving convex
relaxation subproblems. Numerical results suggest that the proposed method
performs well against its alternatives for simulated and real data.
PMID- 24358105
TI - Detection of neovascularization based on fractal and texture analysis with
interaction effects in diabetic retinopathy.
AB - Diabetic retinopathy is a major cause of blindness. Proliferative diabetic
retinopathy is a result of severe vascular complication and is visible as
neovascularization of the retina. Automatic detection of such new vessels would
be useful for the severity grading of diabetic retinopathy, and it is an
important part of screening process to identify those who may require immediate
treatment for their diabetic retinopathy. We proposed a novel new vessels
detection method including statistical texture analysis (STA), high order
spectrum analysis (HOS), fractal analysis (FA), and most importantly we have
shown that by incorporating their associated interactions the accuracy of new
vessels detection can be greatly improved. To assess its performance, the
sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1%
and 98.5% (99.3%), respectively. It is found that the proposed method can improve
the accuracy of new vessels detection significantly over previous methods. The
algorithm can be automated and is valuable to detect relatively severe cases of
diabetic retinopathy among diabetes patients.
PMID- 24358107
TI - Dog behavior co-varies with height, bodyweight and skull shape.
AB - Dogs offer unique opportunities to study correlations between morphology and
behavior because skull shapes and body shape are so diverse among breeds. Several
studies have shown relationships between canine cephalic index (CI: the ratio of
skull width to skull length) and neural architecture. Data on the CI of adult,
show-quality dogs (six males and six females) were sourced in Australia along
with existing data on the breeds' height, bodyweight and related to data on 36
behavioral traits of companion dogs (n = 8,301) of various common breeds (n = 49)
collected internationally using the Canine Behavioral Assessment and Research
Questionnaire (C-BARQ). Stepwise backward elimination regressions revealed that,
across the breeds, 33 behavioral traits all but one of which are undesirable in
companion animals correlated with either height alone (n = 14), bodyweight alone
(n = 5), CI alone (n = 3), bodyweight-and-skull shape combined (n = 2), height
and-skull shape combined (n = 3) or height-and-bodyweight combined (n = 6). For
example, breed average height showed strongly significant inverse relationships
(p<0.001) with mounting persons or objects, touch sensitivity, urination when
left alone, dog-directed fear, separation-related problems, non-social fear,
defecation when left alone, owner-directed aggression, begging for food, urine
marking and attachment/attention-seeking, while bodyweight showed strongly
significant inverse relationships (p<0.001) with excitability and being reported
as hyperactive. Apart from trainability, all regression coefficients with height
were negative indicating that, across the breeds, behavior becomes more
problematic as height decreases. Allogrooming increased strongly (p<0.001) with
CI and inversely with height. CI alone showed a strong significant positive
relationship with self-grooming (p<0.001) but a negative relationship with
chasing (p = 0.020). The current study demonstrates how aspects of CI (and
therefore brain shape), bodyweight and height co-vary with behavior. The
biological basis for, and significance of, these associations remain to be
determined.
PMID- 24358106
TI - Evidence for post-translational processing of vascular endothelial (VE)-cadherin
in brain tumors: towards a candidate biomarker.
AB - Vessel abnormalities are among the most important features in malignant glioma.
Vascular endothelial (VE)-cadherin is of major importance for vascular integrity.
Upon cytokine challenge, VE-cadherin structural modifications have been described
including tyrosine phosphorylation and cleavage. The goal of this study was to
examine whether these events occurred in human glioma vessels. We demonstrated
that VE-cadherin is highly expressed in human glioma tissue and tyrosine
phosphorylated at site Y(685), a site previously found phosphorylated upon VEGF
challenge, via Src activation. In vitro experiments showed that VEGF-induced VE
cadherin phosphorylation, preceded the cleavage of its extracellular adhesive
domain (sVE, 90 kDa). Interestingly, metalloproteases (MMPs) secreted by glioma
cell lines were responsible for sVE release. Because VEGF and MMPs are important
components of tumor microenvironment, we hypothesized that VE-cadherin
proteolysis might occur in human brain tumors. Analysis of glioma patient sera
prior treatment confirmed the presence of sVE in bloodstream. Furthermore, sVE
levels studied in a cohort of 53 glioma patients were significantly predictive of
the overall survival at three years (HR 0.13 [0.04; 0.40] p <= 0.001),
irrespective to histopathological grade of tumors. Altogether, these results
suggest that VE-cadherin structural modifications should be examined as candidate
biomarkers of tumor vessel abnormalities, with promising applications in
oncology.
PMID- 24358108
TI - Relationships between human population density and burned area at continental and
global scales.
AB - We explore the large spatial variation in the relationship between population
density and burned area, using continental-scale Geographically Weighted
Regression (GWR) based on 13 years of satellite-derived burned area maps from the
global fire emissions database (GFED) and the human population density from the
gridded population of the world (GPW 2005). Significant relationships are
observed over 51.5% of the global land area, and the area affected varies from
continent to continent: population density has a significant impact on fire over
most of Asia and Africa but is important in explaining fire over < 22% of Europe
and Australia. Increasing population density is associated with both increased
and decreased in fire. The nature of the relationship depends on land-use:
increasing population density is associated with increased burned are in
rangelands but with decreased burned area in croplands. Overall, the relationship
between population density and burned area is non-monotonic: burned area
initially increases with population density and then decreases when population
density exceeds a threshold. These thresholds vary regionally. Our study
contributes to improved understanding of how human activities relate to burned
area, and should contribute to a better estimate of atmospheric emissions from
biomass burning.
PMID- 24358110
TI - Characteristics and mechanisms of cardiopulmonary injury caused by mine blasts in
shoals: a randomized controlled study in a rabbit model.
AB - BACKGROUND: Because the characteristics of blast waves in water are different
from those in air and because kinetic energy is liberated by a pressure wave at
the water-air interface, thoracic injuries from mine blasts in shoals may be
serious. The aim of the present study was to investigate the characteristics and
mechanisms of cardiopulmonary injury caused by mine blasts in shoals. METHODS: To
study the characteristics of cardiopulmonary injury, 56 animals were divided
randomly into three experimental groups (12 animals in the sham group, 22 animals
in the land group and 22 animals in the shoal group). To examine the biomechanics
of injury, 20 animals were divided randomly into the land group and the shoal
group. In the experimental model, the water surface was at the level of the
rabbit's xiphoid process, and paper electric detonators (600 mg RDX) were used to
simulate mines. Electrocardiography and echocardiography were conducted, and
arterial blood gases, serum levels of cardiac troponin I and creatine kinase-MB
and other physiologic parameters were measured over a 12-hour period after
detonation. Pressures in the thorax and abdomen and the acceleration of the
thorax were measured. CONCLUSION: The results indicate that severe
cardiopulmonary injury and dysfunction occur following exposure to mine blasts in
shoals. Therefore, the mechanisms of cardiopulmonary injury may result from shear
waves that produce strain at the water-air interface. Another mechanism of injury
includes the propagation of the shock wave from the planta to the thorax, which
causes a much higher peak overpressure in the abdomen than in the thorax; as a
result, the abdominal organs and diaphragm are thrust into the thorax, damaging
the lungs and heart.
PMID- 24358109
TI - A systematic review and meta-analysis of the performance of two point of care
typhoid fever tests, Tubex TF and Typhidot, in endemic countries.
AB - BACKGROUND: In the absence of well-equipped laboratory infrastructure in many
developing countries the accurate diagnosis of typhoid fever is challenging.
Rapid diagnostic tests (RDT) with good performance indicators would be helpful to
improve clinical management of suspected cases. We performed a systematic
literature review and meta- analysis to determine the performance of TUBEX TF and
Typhidot for the diagnosis of typhoid fever using PRISMA guidelines. METHODS:
Titles and abstracts were reviewed for relevance. Articles were screened for
language, reference method and completeness. Studies were categorized according
to control groups used. Meta-analysis was performed only for categories where
enough data was available to combine sensitivity and specificity estimates. Sub
analysis was performed for the Typhidot test to determine the influence of
indeterminate results on test performance. RESULTS: A total of seven studies per
test were included. The sensitivity of TUBEX TF ranged between 56% and 95%,
Specificity between 72% and 95%. Meta-analysis showed an average sensitivity of
69% (95%CI: 45-85) and an average specificity of 88% (CI95%:83-91). A formal meta
analysis for Typhidot was not possible due to limited data available. Across the
extracted studies, sensitivity and specificity estimates ranged from 56% to 84%
and 31% to 97% respectively. CONCLUSION: The observed performance does not
support the use of either rapid diagnostic test exclusively as the basis for
diagnosis and treatment. There is a need to develop an RDT for typhoid fever that
has a performance level comparable to malaria RDTs.
PMID- 24358111
TI - Interferon-beta induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral
gene expression by targeting SP1 in cervical cancer cells.
AB - Infection by human papillomavirus (HPV) can cause cervical intraepithelial
neoplasia (CIN) and cancer. Down-regulation of E6 and E7 expression may be
responsible for the positive clinical outcomes observed with IFN treatment, but
the molecular basis has not been well determined. As miRNAs play an important
role in HPV induced cervical carcinogenesis, we hypothesize that IFN-beta can
regulate the expressions of specific miRNAs in cervical cancer cells, and that
these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic
potential. In this study, we found that miR-129-5p to be a candidate IFN-beta
inducible miRNA. MiR-129-5p levels gradually decrease with the development of
cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela
cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p
inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell
cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela
cells. This study is the first report of a cellular miRNA with anti-HPV activity
and provides new insights into regulatory mechanisms between the HPV and the IFN
system in host cells at the miRNA level.
PMID- 24358112
TI - Transplacental transmission of Bluetongue virus serotype 1 and serotype 8 in
sheep: virological and pathological findings.
AB - The Bluetongue virus serotype 8 (BTV-8) strain, which emerged in Europe in 2006,
had an unusually high ability to cause foetal infection in pregnant ruminants.
Other serotypes of BTV had already been present in Europe for more than a decade,
but transplacental transmission of these strains had never been demonstrated. To
determine whether transplacental transmission is a unique feature of BTV-8 we
compared the incidence and pathological consequences of transplacental
transmission of BTV-8 to that of BTV-1. Nine pregnant ewes were infected with
either BTV-8 or BTV-1. The BTV strains used for the infection were field strains
isolated on embryonated chicken eggs and passaged twice on mammalian cells. Blood
samples were taken to monitor the viraemia in the ewes. Four weeks after the
infection, the foetuses were examined for pathological changes and for the
presence of BTV. BTV-8 could be demonstrated in 12 foetuses (43%) from 5 ewes
(56%). %). BTV-1 was detected in 14 foetuses (82%) from 6 ewes (67%).
Pathological changes were mainly found in the central nervous system. In the BTV
8 group, lympho-histiocytic infiltrates, gliosis and slight vacuolation of the
neuropil were found. BTV-1 infection induced a severe necrotizing encephalopathy
and severe meningitis, with macroscopic hydranencephaly or porencephaly in 8
foetuses. In our experimental setting, using low passaged virus strains, BTV-1
was able to induce transplacental transmission to a higher incidence compared to
BTV-8, causing more severe pathology.
PMID- 24358113
TI - Development and application of genomic control methods for genome-wide
association studies using non-additive models.
AB - Genome-wide association studies (GWAS) comprise a powerful tool for mapping genes
of complex traits. However, an inflation of the test statistic can occur because
of population substructure or cryptic relatedness, which could cause spurious
associations. If information on a large number of genetic markers is available,
adjusting the analysis results by using the method of genomic control (GC) is
possible. GC was originally proposed to correct the Cochran-Armitage additive
trend test. For non-additive models, correction has been shown to depend on
allele frequencies. Therefore, usage of GC is limited to situations where allele
frequencies of null markers and candidate markers are matched. In this work, we
extended the capabilities of the GC method for non-additive models, which allows
us to use null markers with arbitrary allele frequencies for GC. Analytical
expressions for the inflation of a test statistic describing its dependency on
allele frequency and several population parameters were obtained for recessive,
dominant, and over-dominant models of inheritance. We proposed a method to
estimate these required population parameters. Furthermore, we suggested a GC
method based on approximation of the correction coefficient by a polynomial of
allele frequency and described procedures to correct the genotypic (two degrees
of freedom) test for cases when the model of inheritance is unknown. Statistical
properties of the described methods were investigated using simulated and real
data. We demonstrated that all considered methods were effective in controlling
type 1 error in the presence of genetic substructure. The proposed GC methods can
be applied to statistical tests for GWAS with various models of inheritance. All
methods developed and tested in this work were implemented using R language as a
part of the GenABEL package.
PMID- 24358114
TI - MicroRNA-146a represses mycobacteria-induced inflammatory response and
facilitates bacterial replication via targeting IRAK-1 and TRAF-6.
AB - BACKGROUND: Apart from triggering host immune responses, macrophages also act as
a major reservoir for mycobacteria. For better survival, mycobacteria have
evolved various mechanisms to modulate the production of proinflammatory
cytokines in macrophages, and manipulation of micro-RNA (miRNA) expression has
been considered as an important one. METHODOLOGY/PRINCIPAL FINDINGS: In this
study, we found that miR-146a expression was significantly increased in a time-
and dose-dependent manner in mycobacteria-infected macrophages. It could
obviously reduce the induction of proinflammatory cytokines TNF-alpha, IL-1beta,
IL-6 and chemokine MCP-1 by targeting interleukin-1 receptor-associated kinase-1
(IRAK-1) and TNF receptor-associated factor-6 (TRAF-6), two key elements involved
in the TLR/NF-kappaB signaling pathway cascades. Consistent with the anti
inflammation effect, a higher bacterial burden was seen in miR-146a mimics
treated macrophages. CONCLUSION/SIGNIFICANCE: Here, we demonstrated that
mycobacteria-induced miR-146a could modulate inflammatory response by targeting
IRAK1 and TRAF6 and facilitate mycobacteria replication in macrophages.
PMID- 24358115
TI - Morals matter in economic games.
AB - Contrary to predictions from Expected Utility Theory and Game Theory, when making
economic decisions in interpersonal situations, people take the interest of
others into account and express various forms of solidarity, even in one-shot
interactions with anonymous strangers. Research in other-regarding behavior is
dominated by behavioral economical and evolutionary biological approaches.
Psychological theory building, which addresses mental processes underlying other
regarding behavior, is rare. Based on Relational Models Theory (RMT, [1]) and
Relationship Regulation Theory (RRT, [2]) it is proposed that moral motives
influence individuals' decision behavior in interpersonal situations via
conscious and unconscious (automatic) processes. To test our propositions we
developed the 'Dyadic Solidarity Game' and its solitary equivalent, the 'Self
Insurance Game'. Four experiments, in which the moral motives "Unity" and
"Proportionality" were manipulated, support the propositions made. First, it was
shown that consciously activated moral motives (via framing of the overall goal
of the experiment) and unconsciously activated moral motives (via subliminal
priming) influence other-regarding behavior. Second, this influence was only
found in interpersonal, not in solitary situations. Third, by combining the
analyses of the two experimental games the extent to which participants apply the
Golden Rule ("treat others how you wish to be treated") could be established.
Individuals with a "Unity" motive treated others like themselves, whereas
individuals with a "Proportionality" motive gave others less then they gave
themselves. The four experiments not only support the assumption that morals
matter in economic games, they also deliver new insights in how morals matter in
economic decision making.
PMID- 24358116
TI - Detailed analysis of the microbial population in Malaysian spontaneous cocoa pulp
fermentations reveals a core and variable microbiota.
AB - The fermentation of cocoa pulp is one of the few remaining large-scale
spontaneous microbial processes in today's food industry. The microbiota involved
in cocoa pulp fermentations is complex and variable, which leads to inconsistent
production efficiency and cocoa quality. Despite intensive research in the field,
a detailed and comprehensive analysis of the microbiota is still lacking,
especially for the expanding Asian production region. Here, we report a large
scale, comprehensive analysis of four spontaneous Malaysian cocoa pulp
fermentations across two time points in the harvest season and two fermentation
methods. Our results show that the cocoa microbiota consists of a "core" and a
"variable" part. The bacterial populations show a remarkable consistency, with
only two dominant species, Lactobacillus fermentum and Acetobacter pasteurianus.
The fungal diversity is much larger, with four dominant species occurring in all
fermentations ("core" yeasts), and a large number of yeasts that only occur in
lower numbers and specific fermentations ("variable" yeasts). Despite this
diversity, a clear pattern emerges, with early dominance of apiculate yeasts and
late dominance of Saccharomyces cerevisiae. Our results provide new insights into
the microbial diversity in Malaysian cocoa pulp fermentations and pave the way
for the selection of starter cultures to increase efficiency and consistency.
PMID- 24358117
TI - High connectivity of animal populations in deep-sea hydrothermal vent fields in
the Central Indian Ridge relevant to its geological setting.
AB - Dispersal ability plays a key role in the maintenance of species in spatially and
temporally discrete niches of deep-sea hydrothermal vent environments. On the
basis of population genetic analyses in the eastern Pacific vent fields,
dispersal of animals in the mid-oceanic ridge systems generally appears to be
constrained by geographical barriers such as trenches, transform faults, and
microplates. Four hydrothermal vent fields (the Kairei and Edmond fields near the
Rodriguez Triple Junction, and the Dodo and Solitaire fields in the Central
Indian Ridge) have been discovered in the mid-oceanic ridge system of the Indian
Ocean. In the present study, we monitored the dispersal of four representative
animals, Austinograea rodriguezensis, Rimicaris kairei, Alviniconcha and the
scaly-foot gastropods, among these vent fields by using indirect methods, i.e.,
phylogenetic and population genetic analyses. For all four investigated species,
we estimated potentially high connectivity, i.e., no genetic difference among the
populations present in vent fields located several thousands of kilometers apart;
however, the direction of migration appeared to differ among the species,
probably because of different dispersal strategies. Comparison of the
intermediate-spreading Central Indian Ridge with the fast-spreading East Pacific
Rise and slow-spreading Mid-Atlantic Ridge revealed the presence of relatively
high connectivity in the intermediate- and slow-spreading ridge systems. We
propose that geological background, such as spreading rate which determines
distance among vent fields, is related to the larval dispersal and population
establishment of vent-endemic animal species, and may play an important role in
controlling connectivity among populations within a biogeographical province.
PMID- 24358118
TI - Interaction network of proteins associated with human cytomegalovirus IE2-p86
protein during infection: a proteomic analysis.
AB - Human cytomegalovirus protein IE2-p86 exerts its functions through interaction
with other viral and cellular proteins. To further delineate its protein
interaction network, we generated a recombinant virus expressing SG-tagged IE2
p86 and used tandem affinity purification coupled with mass spectrometry. A total
of 9 viral proteins and 75 cellular proteins were found to associate with IE2-p86
protein during the first 48 hours of infection. The protein profile at 8, 24, and
48 h post infection revealed that UL84 tightly associated with IE2-p86, and more
viral and cellular proteins came into association with IE2-p86 with the
progression of virus infection. A computational analysis of the protein-protein
interaction network indicated that all of the 9 viral proteins and most of the
cellular proteins identified in the study are interconnected to varying degrees.
Of the cellular proteins that were confirmed to associate with IE2-p86 by
immunoprecipitation, C1QBP was further shown to be upregulated by HCMV infection
and colocalized with IE2-p86, UL84 and UL44 in the virus replication compartment
of the nucleus. The IE2-p86 interactome network demonstrated the temporal
development of stable and abundant protein complexes that associate with IE2-p86
and provided a framework to benefit future studies of various protein complexes
during HCMV infection.
PMID- 24358119
TI - Effects of intra-amniotic lipopolysaccharide and maternal betamethasone on brain
inflammation in fetal sheep.
AB - RATIONALE: Chorioamnionitis and antenatal glucocorticoids are common exposures
for preterm infants and can affect the fetal brain, contributing to cognitive and
motor deficits in preterm infants. The effects of antenatal glucocorticoids on
the brain in the setting of chorioamnionitis are unknown. We hypothesized that
antenatal glucocorticoids would modulate inflammation in the brain and prevent
hippocampal and white matter injury after intra-amniotic lipopolysaccharide (LPS)
exposure. METHODS: Time-mated ewes received saline (control), an intra-amniotic
injection of 10 mg LPS at 106d GA or 113d GA, maternal intra-muscular
betamethasone (0.5 mg/kg maternal weight) alone at 113d GA, betamethasone at 106d
GA before LPS or betamethasone at 113d GA after LPS. Animals were delivered at
120d GA (term=150d). Brain structure volumes were measured on T2-weighted MRI
images. The subcortical white matter (SCWM), periventricular white matter (PVWM)
and hippocampus were analyzed for microglia, astrocytes, apoptosis,
proliferation, myelin and pre-synaptic vesicles. RESULTS: LPS and/or
betamethasone exposure at different time-points during gestation did not alter
brain structure volumes on MRI. Betamethasone alone did not alter any of the
measurements. Intra-amniotic LPS at 106d or 113d GA induced inflammation as
indicated by increased microglial and astrocyte recruitment which was paralleled
by increased apoptosis and hypomyelination in the SCWM and decreased
synaptophysin density in the hippocampus. Betamethasone before the LPS exposure
at 113d GA prevented microglial activation and the decrease in synaptophysin.
Betamethasone after LPS exposure increased microglial infiltration and apoptosis.
CONCLUSION: Intra-uterine LPS exposure for 7d or 14d before delivery induced
inflammation and injury in the fetal white matter and hippocampus. Antenatal
glucocorticoids aggravated the inflammatory changes in the brain caused by pre
existing intra-amniotic inflammation. Antenatal glucocorticoids prior to LPS
reduced the effects of intra-uterine inflammation on the brain. The timing of
glucocorticoid administration in the setting of chorioamnionitis can alter
outcomes for the fetal brain.
PMID- 24358120
TI - The effect of correlated neuronal firing and neuronal heterogeneity on population
coding accuracy in guinea pig inferior colliculus.
AB - It has been suggested that the considerable noise in single-cell responses to a
stimulus can be overcome by pooling information from a large population.
Theoretical studies indicated that correlations in trial-to-trial fluctuations in
the responses of different neurons may limit the improvement due to pooling.
Subsequent theoretical studies have suggested that inherent neuronal diversity,
i.e., the heterogeneity of tuning curves and other response properties of neurons
preferentially tuned to the same stimulus, can provide a means to overcome this
limit. Here we study the effect of spike-count correlations and the inherent
neuronal heterogeneity on the ability to extract information from large neural
populations. We use electrophysiological data from the guinea pig Inferior
Colliculus to capture inherent neuronal heterogeneity and single cell statistics,
and introduce response correlations artificially. To this end, we generate pseudo
population responses, based on single-cell recording of neurons responding to
auditory stimuli with varying binaural correlations. Typically, when pseudo
populations are generated from single cell data, the responses within the
population are statistically independent. As a result, the information content of
the population will increase indefinitely with its size. In contrast, here we
apply a simple algorithm that enables us to generate pseudo-population responses
with variable spike-count correlations. This enables us to study the effect of
neuronal correlations on the accuracy of conventional rate codes. We show that in
a homogenous population, in the presence of even low-level correlations,
information content is bounded. In contrast, utilizing a simple linear readout,
that takes into account the natural heterogeneity, even of neurons preferentially
tuned to the same stimulus, within the neural population, one can overcome the
correlated noise and obtain a readout whose accuracy grows linearly with the size
of the population.
PMID- 24358121
TI - Immunoproteomic to identify antigens in the intestinal mucosa of Crohn's disease
patients.
AB - Incidences of Crohn disease (CD) have increased significantly in the last decade.
Immunoproteomics are a promising method to identify biomarkers of different
diseases. In the present study, we used immunoproteomics to study proteins of
intestinal mucosal lesions and neighboring normal intestinal mucosa of 8 CD
patients. Reactive proteins were validated by Western blotting. Approximately 50
protein spots localized in the 4 to 7 pI range were detected on two-dimensional
electrophoresis gels, and 6 differentially expressed protein spots between 10 and
100 kDa were identified. Reactive proteins were identified as prohibitin,
calreticulin, apolipoprotein A-I, intelectin-1, protein disulfide isomerase, and
glutathione s-transferase Pi. Western blotting was conducted on the intestinal
mucosa of another 4 CD patients to validate the reactive proteins. We found that
intestinal mucosal lesions had high levels of prohibitin expression. Glutathione
s-transferase expression was detected in 100% of the intestinal mucosa examined.
Thus, we report 6 autoantigens of CD, including 3 new and 3 previously reported
autoantigens. Intelectin-1, protein disulfide isomerase, and glutathione-s
transferases may be used as biomarkers for CD pathogenesis.
PMID- 24358122
TI - The role of adhesion molecules as biomarkers for the aggressive prostate cancer
phenotype.
AB - BACKGROUND: Currently available methods for diagnosis and staging of prostate
cancer lack the sensitivity to distinguish between patients with indolent
prostate cancer and those requiring radical treatment. Alterations in key
adherens (AJ) and tight junction (TJ) components have been hailed as potential
biomarkers for prostate cancer progression but the majority of research has been
carried out on individual molecules. OBJECTIVE: To elucidate a panel of
biomarkers that may help distinguish dormant prostate cancer from aggressive
metastatic disease. METHODS: We analysed the expression of 7 well known AJ and TJ
components in cell lines derived from normal prostate epithelial tissue (PNT2),
non-invasive (CAHPV-10) and invasive prostate cancer (LNCaP, DU145, PC-3) using
gene expression, western blotting and immunofluorescence techniques. RESULTS:
Claudin 7, alpha -catenin and beta-catenin protein expression were not
significantly different between CAHPV-10 cells and PNT2 cells. However, in PC-3
cells, protein levels for claudin 7, alpha -catenin were significantly down
regulated (-1.5 fold, p = <.001) or undetectable respectively. Immunofluoresence
showed beta-catenin localisation in PC-3 cells to be cytoplasmic as opposed to
membraneous. CONCLUSION: These results suggest aberrant Claudin 7, alpha - and
beta-catenin expression and/or localisation patterns may be putative markers for
distinguishing localised prostate cancer from aggressive metastatic disease when
used collectively.
PMID- 24358123
TI - High HIV incidence among persons who inject drugs in Pakistan: greater risk with
needle sharing and injecting frequently among the homeless.
AB - BACKGROUND: The incidence of HIV among persons who inject drugs (PWIDU) has
fallen in many nations, likely due to successes of clean needle/syringe exchange
and substance abuse treatment and service programs. However in Pakistan,
prevalence rates for PWID have risen dramatically. In several cities, prevalence
exceeded 20% by 2009 compared to a 2003 baseline of just 0.5%. However, no cohort
study of PWID has ever been conducted. METHODS: We enrolled a cohort of 636 HIV
seronegative PWID registered with three drop-in centers that focus on risk
reduction and basic social services in Karachi. Recruitment began in 2009 (March
to June) and PWID were followed for two years. We measured incidence rates and
risk factors associated with HIV seroconversion. RESULTS: Incidence of HIV was
12.4 per 100 person-years (95% exact Poisson confidence interval [CI]: 10.3
14.9). We followed 474 of 636 HIV seronegative persons (74.5%) for two years, an
annual loss to follow-up of <13 per 100 person years. In multivariable Cox
regression analysis, HIV seroconversion was associated with non-Muslim religion
(Adjusted risk ratio [ARR] = 1.7, 95%CI:1.4, 2.7, p = 0.03), sharing of syringes
(AR = 2.3, 95%CI:1.5, 3.3, p<0.0001), being homeless (ARR = 1.7, 95%CI:1.1, 2.5,
p = 0.009), and daily injection of drugs (ARR = 1.1, 95%CI:1.0, 1.3, p = 0.04).
CONCLUSIONS: Even though all members of the cohort of PWID were attending risk
reduction programs, the HIV incidence rate was very high in Karachi from 2009
2011. The project budget was low, yet we were able to retain three-quarters of
the population over two years. Absence of opiate substitution therapy and
incomplete needle/syringe exchange coverage undermines success in HIV risk
reduction.
PMID- 24358124
TI - Ion Torrent PGM as tool for fungal community analysis: a case study of endophytes
in Eucalyptus grandis reveals high taxonomic diversity.
AB - The Kingdom Fungi adds substantially to the diversity of life, but due to their
cryptic morphology and lifestyle, tremendous diversity, paucity of formally
described specimens, and the difficulty in isolating environmental strains into
culture, fungal communities are difficult to characterize. This is especially
true for endophytic communities of fungi living in healthy plant tissue. The
developments in next generation sequencing technologies are, however, starting to
reveal the true extent of fungal diversity. One of the promising new
technologies, namely semiconductor sequencing, has thus far not been used in
fungal diversity assessments. In this study we sequenced the internal transcribed
spacer 1 (ITS1) nuclear encoded ribosomal RNA of the endophytic community of the
economically important tree, Eucalyptus grandis, from South Africa using the Ion
Torrent Personal Genome Machine (PGM). We determined the impact of various
analysis parameters on the interpretation of the results, namely different
sequence quality parameter settings, different sequence similarity cutoffs for
clustering and filtering of databases for removal of sequences with incomplete
taxonomy. Sequence similarity cutoff values only had a marginal effect on the
identified family numbers, whereas different sequence quality filters had a large
effect (89 vs. 48 families between least and most stringent filters). Database
filtering had a small, but statistically significant, effect on the assignment of
sequences to reference sequences. The community was dominated by Ascomycota, and
particularly by families in the Dothidiomycetes that harbor well-known plant
pathogens. The study demonstrates that semiconductor sequencing is an ideal
strategy for environmental sequencing of fungal communities. It also highlights
some potential pitfalls in subsequent data analyses when using a technology with
relatively short read lengths.
PMID- 24358125
TI - On the applicability of brain reading for predictive human-machine interfaces in
robotics.
AB - The ability of today's robots to autonomously support humans in their daily
activities is still limited. To improve this, predictive human-machine interfaces
(HMIs) can be applied to better support future interaction between human and
machine. To infer upcoming context-based behavior relevant brain states of the
human have to be detected. This is achieved by brain reading (BR), a passive
approach for single trial EEG analysis that makes use of supervised machine
learning (ML) methods. In this work we propose that BR is able to detect concrete
states of the interacting human. To support this, we show that BR detects
patterns in the electroencephalogram (EEG) that can be related to event-related
activity in the EEG like the P300, which are indicators of concrete states or
brain processes like target recognition processes. Further, we improve the
robustness and applicability of BR in application-oriented scenarios by
identifying and combining most relevant training data for single trial
classification and by applying classifier transfer. We show that training and
testing, i.e., application of the classifier, can be carried out on different
classes, if the samples of both classes miss a relevant pattern. Classifier
transfer is important for the usage of BR in application scenarios, where only
small amounts of training examples are available. Finally, we demonstrate a dual
BR application in an experimental setup that requires similar behavior as
performed during the teleoperation of a robotic arm. Here, target recognition
processes and movement preparation processes are detected simultaneously. In
summary, our findings contribute to the development of robust and stable
predictive HMIs that enable the simultaneous support of different interaction
behaviors.
PMID- 24358126
TI - Rab GTPase prenylation hierarchy and its potential role in choroideremia disease.
AB - Protein prenylation is a widespread post-translational modification in eukaryotes
that plays a crucial role in membrane targeting and signal transduction.
RabGTPases is the largest group of post-translationally C-terminally
geranylgeranylated. All Rabs are processed by Rab geranylgeranyl-transferase and
Rab escort protein (REP). Human genetic defects resulting in the loss one of two
REP isoforms REP-1, lead to underprenylation of RabGTPases that manifests in
retinal degradation and blindness known as choroideremia. In this study we used a
combination of microinjections and chemo-enzymatic tagging to establish whether
Rab GTPases are prenylated and delivered to their target cellular membranes with
the same rate. We demonstrate that although all tested Rab GTPases display the
same rate of membrane delivery, the extent of Rab prenylation in 5 hour time
window vary by more than an order of magnitude. We found that Rab27a, Rab27b,
Rab38 and Rab42 display the slowest prenylation in vivo and in the cell. Our work
points to possible contribution of Rab38 to the emergence of choroideremia in
addition to Rab27a and Rab27b.
PMID- 24358129
TI - Critical analysis of the Bennett-Riedel attack on secure cryptographic key
distributions via the Kirchhoff-Law-Johnson-noise scheme.
AB - Recently, Bennett and Riedel (BR) (http://arxiv.org/abs/1303.7435v1) argued that
thermodynamics is not essential in the Kirchhoff-law-Johnson-noise (KLJN)
classical physical cryptographic exchange method in an effort to disprove the
security of the KLJN scheme. They attempted to demonstrate this by introducing a
dissipation-free deterministic key exchange method with two batteries and two
switches. In the present paper, we first show that BR's scheme is unphysical and
that some elements of its assumptions violate basic protocols of secure
communication. All our analyses are based on a technically unlimited Eve with
infinitely accurate and fast measurements limited only by the laws of physics and
statistics. For non-ideal situations and at active (invasive) attacks, the
uncertainly principle between measurement duration and statistical errors makes
it impossible for Eve to extract the key regardless of the accuracy or speed of
her measurements. To show that thermodynamics and noise are essential for the
security, we crack the BR system with 100% success via passive attacks, in ten
different ways, and demonstrate that the same cracking methods do not function
for the KLJN scheme that employs Johnson noise to provide security underpinned by
the Second Law of Thermodynamics. We also present a critical analysis of some
other claims by BR; for example, we prove that their equations for describing
zero security do not apply to the KLJN scheme. Finally we give mathematical
security proofs for each BR-attack against the KLJN scheme and conclude that the
information theoretic (unconditional) security of the KLJN method has not been
successfully challenged.
PMID- 24358128
TI - Interleukin-21 receptor signalling is important for innate immune protection
against HSV-2 infections.
AB - Interleukin (IL) -21 is produced by Natural Killer T (NKT) cells and CD4(+) T
cells and is produced in response to virus infections, where IL-21 has been shown
to be essential in adaptive immune responses. Cells from the innate immune system
such as Natural Killer (NK) cells and macrophages are also important in immune
protection against virus. These cells express the IL-21 receptor (IL-21R) and
respond to IL-21 with increased cytotoxicity and cytokine production. Currently,
however it is not known whether IL-21 plays a significant role in innate immune
responses to virus infections. The purpose of this study was to investigate the
role of IL-21 and IL-21R in the innate immune response to a virus infection. We
used C57BL/6 wild type (WT) and IL-21R knock out (KO) mice in a murine vaginal
Herpes Simplex Virus type 2 (HSV-2) infection model to show that IL-21 - IL-21R
signalling is indeed important in innate immune responses against HSV-2. We found
that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i) WT
mice, and expression increased early after HSV-2 infection. IL-21R KO mice
exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i.) and
subsequently developed significantly higher disease scores and a lower survival
rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving
intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21) had decreased
vaginal viral titers on day 2 p.i., significantly lower disease scores, and a
higher survival rate compared to infected untreated WT controls. Collectively our
data demonstrate the novel finding that the IL-21R plays a critical role in
regulating innate immune responses against HSV-2 infection.
PMID- 24358127
TI - IL-4/IL-13-dependent and independent expression of miR-124 and its contribution
to M2 phenotype of monocytic cells in normal conditions and during allergic
inflammation.
AB - Monocytic cells exhibit a high level of heterogeneity and have two distinct modes
of their activation: 1) classical M1 path associated with inflammation and tissue
damage, and 2) alternative M2 path. Although it has been demonstrated that M2
macrophages play an important role in the regulation of the allergic immune
responses, tissue maintenance and repair, little is known about the mechanisms
that determine the M2 phenotype. We have previously shown that miR-124 is
expressed in microglia that exhibit the M2 phenotype and overexpression of miR
124 in macrophages resulted in downregulation of a number of M1 markers (MHC
class II, CD86) and up-regulation of several M2 markers (Fizz1, Arg1). We further
investigated whether the polarization of macrophages towards the M2 phenotype
induced miR-124 expression. We found that exposure of cells to IL-4 and IL-13
resulted in the upregulation of miR-124 in macrophages. We also demonstrated that
IL-4 induced expression of three miR-124 precursor transcripts with predominant
expression of pri-miR-124.3, suggesting regulation of miR-124 expression by IL-4
on a transcriptional level. Expression of miR-124 in microglia did not depend on
IL-4 and/or IL-13, whereas expression of miR-124 in lung resident macrophages was
IL-4 and IL-13-dependent and was upregulated by systemic administration of IL-4
or during allergic inflammation. Upregulation of several M2 markers (CD206, Ym1)
and downregulation of the M1 markers (CD86, iNOS, TNF) in M2-polarized
macrophages was abrogated by a miR-124 inhibitor, suggesting that this microRNA
contributed to the M2 phenotype development and maintenance. Finally we showed
that human CD14(+)CD16(+) intermediate monocytes, which are found in increased
numbers in patients with allergies and bronchial asthma, expressed high levels of
miR-124 and exhibited other properties of M2-like cells. Thus, our study suggests
that miR-124 serves as a regulator of the M2 polarization in various subsets of
monocytic cells both in vitro and in vivo.
PMID- 24358130
TI - Aging in mice reduces the ability to sustain sleep/wake states.
AB - One of the most significant problems facing older individuals is difficulty
staying asleep at night and awake during the day. Understanding the mechanisms by
which the regulation of sleep/wake goes awry with age is a critical step in
identifying novel therapeutic strategies to improve quality of life for the
elderly. We measured wake, non-rapid eye movement (NREM) and rapid-eye movement
(REM) sleep in young (2-4 months-old) and aged (22-24 months-old) C57BL6/NIA
mice. We used both conventional measures (i.e., bout number and bout duration)
and an innovative spike-and-slab statistical approach to characterize age-related
fragmentation of sleep/wake. The short (spike) and long (slab) components of the
spike-and-slab mixture model capture the distribution of bouts for each
behavioral state in mice. Using this novel analytical approach, we found that
aged animals are less able to sustain long episodes of wakefulness or NREM sleep.
Additionally, spectral analysis of EEG recordings revealed that aging slows theta
peak frequency, a correlate of arousal. These combined analyses provide a window
into the mechanisms underlying the destabilization of long periods of sleep and
wake and reduced vigilance that develop with aging.
PMID- 24358132
TI - Automatic segmentation of eight tissue classes in neonatal brain MRI.
AB - PURPOSE: Volumetric measurements of neonatal brain tissues may be used as a
biomarker for later neurodevelopmental outcome. We propose an automatic method
for probabilistic brain segmentation in neonatal MRIs. MATERIALS AND METHODS: In
an IRB-approved study axial T1- and T2-weighted MR images were acquired at term
equivalent age for a preterm cohort of 108 neonates. A method for automatic
probabilistic segmentation of the images into eight cerebral tissue classes was
developed: cortical and central grey matter, unmyelinated and myelinated white
matter, cerebrospinal fluid in the ventricles and in the extra cerebral space,
brainstem and cerebellum. Segmentation is based on supervised pixel
classification using intensity values and spatial positions of the image voxels.
The method was trained and evaluated using leave-one-out experiments on seven
images, for which an expert had set a reference standard manually. Subsequently,
the method was applied to the remaining 101 scans, and the resulting
segmentations were evaluated visually by three experts. Finally, volumes of the
eight segmented tissue classes were determined for each patient. RESULTS: The
Dice similarity coefficients of the segmented tissue classes, except myelinated
white matter, ranged from 0.75 to 0.92. Myelinated white matter was difficult to
segment and the achieved Dice coefficient was 0.47. Visual analysis of the
results demonstrated accurate segmentations of the eight tissue classes. The
probabilistic segmentation method produced volumes that compared favorably with
the reference standard. CONCLUSION: The proposed method provides accurate
segmentation of neonatal brain MR images into all given tissue classes, except
myelinated white matter. This is the one of the first methods that distinguishes
cerebrospinal fluid in the ventricles from cerebrospinal fluid in the
extracerebral space. This method might be helpful in predicting
neurodevelopmental outcome and useful for evaluating neuroprotective clinical
trials in neonates.
PMID- 24358131
TI - A genome-wide search for linkage of estimated glomerular filtration rate (eGFR)
in the Family Investigation of Nephropathy and Diabetes (FIND).
AB - OBJECTIVE: Estimated glomerular filtration rate (eGFR), a measure of kidney
function, is heritable, suggesting that genes influence renal function. Genes
that influence eGFR have been identified through genome-wide association studies.
However, family-based linkage approaches may identify loci that explain a larger
proportion of the heritability. This study used genome-wide linkage and
association scans to identify quantitative trait loci (QTL) that influence eGFR.
METHODS: Genome-wide linkage and sparse association scans of eGFR were performed
in families ascertained by probands with advanced diabetic nephropathy (DN) from
the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study.
This study included 954 African Americans (AA), 781 American Indians (AI), 614
European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND
participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs)
using the Illumina Linkage IVb panel. GFR was estimated by the Modification of
Diet in Renal Disease (MDRD) formula. RESULTS: The non-parametric linkage
analysis, accounting for the effects of diabetes duration and BMI, identified the
strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD]
= 3.34; P = 4.4 * 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 * 10(
4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on
chromosome 10p12 (P = 5.5 * 10(-4)) at 44 cM near marker rs1339048. A subsequent
association scan in both ancestry-specific groups and the entire population
identified several SNPs significantly associated with eGFR across the genome.
CONCLUSION: The present study describes the localization of QTL influencing eGFR
on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating
in the FIND study. Identification of causal genes/variants influencing eGFR,
within these linkage and association loci, will open new avenues for functional
analyses and development of novel diagnostic markers for DN.
PMID- 24358133
TI - Revisiting the estimation of dinosaur growth rates.
AB - Previous growth-rate studies covering 14 dinosaur taxa, as represented by 31 data
sets, are critically examined and reanalyzed by using improved statistical
techniques. The examination reveals that some previously reported results cannot
be replicated by using the methods originally reported; results from new methods
are in many cases different, in both the quantitative rates and the qualitative
nature of the growth, from results in the prior literature. Asymptotic growth
curves, which have been hypothesized to be ubiquitous, are shown to provide best
fits for only four of the 14 taxa. Possible reasons for non-asymptotic growth
patterns are discussed; they include systematic errors in the age-estimation
process and, more likely, a bias toward younger ages among the specimens
analyzed. Analysis of the data sets finds that only three taxa include specimens
that could be considered skeletally mature (i.e., having attained 90% of maximum
body size predicted by asymptotic curve fits), and eleven taxa are quite
immature, with the largest specimen having attained less than 62% of predicted
asymptotic size. The three taxa that include skeletally mature specimens are
included in the four taxa that are best fit by asymptotic curves. The totality of
results presented here suggests that previous estimates of both maximum dinosaur
growth rates and maximum dinosaur sizes have little statistical support.
Suggestions for future research are presented.
PMID- 24358134
TI - Ras and Rac1, frequently mutated in melanomas, are activated by superoxide anion,
modulate Dnmt1 level and are causally related to melanocyte malignant
transformation.
AB - A melanocyte malignant transformation model was developed in our laboratory, in
which different melanoma cell lines were obtained after submitting the non
tumorigenic melanocyte lineage melan-a to sequential cycles of anchorage
impediment. Our group has already showed that increased superoxide level leads to
global DNA hypermemethylation as well increased Dnmt1 expression few hours after
melanocyte anchorage blockade. Here, we showed that Ras/Rac1/ERK signaling
pathway is activated in melanocytes submitted to anchorage impediment, regulating
superoxide levels, global DNA methylation, and Dnmt1 expression. Interestingly,
Ras and Rac1 activation is not related to codon mutations, but instead regulated
by superoxide. Moreover, the malignant transformation was drastically compromised
when melan-a melanocytes were submitted to sequential cycles of anchorage
blockage in the presence of a superoxide scavenger. This aberrant signaling
pathway associated with a sustained stressful condition, which might be similar
to conditions such as UV radiation and inflammation, seems to be an early step in
malignant transformation and to contribute to an epigenetic reprogramming and the
melanoma development.
PMID- 24358135
TI - The effect of static stretch on elastin degradation in arteries.
AB - Previously we have shown that gradual changes in the structure of elastin during
an elastase treatment can lead to important transition stages in the mechanical
behavior of arteries. However, in vivo arteries are constantly being loaded due
to systolic and diastolic pressures and so understanding the effects of loading
on the enzymatic degradation of elastin in arteries is important. With biaxial
tensile testing, we measured the mechanical behavior of porcine thoracic aortas
digested with a mild solution of purified elastase (5 U/mL) in the presence of a
static stretch. Arterial mechanical properties and biochemical composition were
analyzed to assess the effects of mechanical stretch on elastin degradation. As
elastin is being removed, the dimensions of the artery increase by more than 20%
in both the longitude and circumference directions. Elastin assays indicate a
faster rate of degradation when stretch was present during the digestion. A
simple exponential decay fitting confirms the time constant for digestion with
stretch (0.11 +/- 0.04 h(-1)) is almost twice that of digestion without stretch
(0.069 +/- 0.028 h(-1)). The transition from J-shaped to S-shaped stress vs.
strain behavior in the longitudinal direction generally occurs when elastin
content is reduced by about 60%. Multiphoton image analysis confirms the
removal/fragmentation of elastin and also shows that the collagen fibers are
closely intertwined with the elastin lamellae in the medial layer. After removal
of elastin, the collagen fibers are no longer constrained and become disordered.
Release of amorphous elastin during the fragmentation of the lamellae layers is
observed and provides insights into the process of elastin degradation. Overall
this study reveals several interesting microstructural changes in the
extracellular matrix that could explain the resulting mechanical behavior of
arteries with elastin degradation.
PMID- 24358136
TI - Myocardial scar identified by magnetic resonance imaging can predict left
ventricular functional improvement after coronary artery bypass grafting.
AB - BACKGROUND: Previous studies have shown that viable myocardium predicts recovery
of left ventricular (LV) dysfunction after revascularization. Our aim was to
evaluate the prognostic value of myocardial scar assessed by late gadolinium
enhanced cardiovascular magnetic resonance imaging (LGE-CMR) on functional
recovery in patients undergoing coronary artery bypass grafting (CABG). METHODS:
From November 2009 to September 2012, 63 patients with reduced left ventricular
ejection fraction (LVEF) referred for first-time isolated CABG were prospectively
enrolled, 52 were included in final analysis. LV functional parameters and scar
tissue were assessed by LGE-CMR at baseline and 6 months after surgery. Patency
of grafts was evaluated by computed tomography angiography (CTA) 6 months post
CABG. Predictors for global functional recovery were analyzed. RESULTS: The
baseline LVEF was 32.7 +/- 9.2%, which improved to 41.6 +/- 11.0% 6 months later
and 32/52 patients improved LVEF by >= 5%. Multivariate logistic regression
analysis showed that the most significant negative predictor for global
functional recovery was the number of scar segments (Odds ratio 2.864, 95%
Confidence Interval 1.172-6.996, p = 0.021). Receiver-Operator-Characteristic
(ROC) analysis demonstrated that <= 4 scar segments predicted global functional
recovery with a sensitivity and specificity of 85.0% and 87.5%, respectively (AUC
= 0.91, p<0.001). Comparison of ROC curves also indicated that scar tissue was
superior to viable myocardium in predicting cardiac functional recovery
(p<0.001). CONCLUSIONS: Our findings indicated that scar tissue on LGE-CMR is an
independent negative predictor of cardiac functional recovery in patients with
impaired LV function undergoing CABG. These observations may be helpful for
clinicians and cardiovascular surgeons to determine which patients are most
likely to benefit from surgical revascularization.
PMID- 24358137
TI - X-ray solution scattering of squid heavy meromyosin: strengthening the evidence
for an ancient compact off state.
AB - The overall conformations of regulated myosins or heavy meromyosins from
chicken/turkey, scallop, tarantula, limulus, and scorpion sources have been
studied by a number of techniques, including electron microscopy, sedimentation,
and pulsed electron paramagnetic resonance. These studies have indicated that the
binding of regulatory ions changes the conformation of the molecule from a
compact shape found in the "off" state of the muscle to extended relationships
between the tail and independently mobile heads that predominate in the "on"
state. Here we strengthen the argument for the generality of this conformational
change by using small angle X-ray scattering on heavy meromyosin from squid.
Small angle X-ray scattering allows the protein to be visualized in solution
under mild and relatively physiological conditions, and squid differs from the
other species studied by at least 500 million years of evolution. Analysis of the
data indicates that upon addition of Ca(2+) the radius of gyration increases.
Differences in the squid "on" and "off" states are clearly distinguishable as
bimodal and unimodal pair distance distribution functions respectively. These
observations are consistent with a Ca(2+)-free squid heavy meromyosin that is
compact, but which becomes extended when Ca(2+) is bound. Further, the scattering
profile derived from the current model of tarantula heavy meromyosin in the "off"
state is in excellent agreement with the measured "off" state scattering profile
for squid heavy meromyosin. The previous and current studies together provide
significant evidence that regulated myosin's compact off-state conformation is an
ancient trait, inherited from a common ancestor during divergent evolution.
PMID- 24358138
TI - Identification of Navbeta1 residues involved in the modulation of the sodium
channel Nav1.4.
AB - Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that
initiate action potentials in excitable cells. The voltage-gated sodium channel
accessory subunit, Navbeta1, allosterically modulates the alpha subunit pore
structure upon binding. To date, the molecular determinants of the interface
remain unknown. We made use of sequence, knowledge and structure-based methods to
identify residues critical to the association of the alpha and beta1 Nav1.4
subunits. The Navbeta1 point mutant C43A disrupted the modulation of voltage
dependence of activation and inactivation and delayed the peak current decay, the
recovery from inactivation, and induced a use-dependent decay upon depolarisation
at 1 Hz. The Navbeta1 mutant R89A selectively delayed channel inactivation and
recovery from inactivation and had no effect on voltage dependence or repetitive
depolarisations. Navbeta1 mutants Y32A and G33M selectively modified the half
voltage of inactivation without altering the kinetics. Despite low sequence
identity, highly conserved structural elements were identified. Our models were
consistent with published data and may help relate pathologies associated with
VGSCs to the Navbeta1 subunit.
PMID- 24358139
TI - Isolation and characterization of a single-stranded DNA virus infecting the
marine diatom Chaetoceros sp. strain SS628-11 isolated from western Japan.
AB - Diatoms are significant organisms for primary production in the earth's aquatic
environment. Hence, their dynamics are an important focus area in current
studies. Viruses are a great concern as potential factors of diatom mortality,
along with other physical, chemical, and biological factors. We isolated and
characterized a new diatom virus (Csp07DNAV) that lyses the marine planktonic
diatom Chaetoceros sp. strain SS628-11. This paper examines the physiological,
morphological, and genomic characteristics of Csp07DNAV. The virus was isolated
from a surface water sample that was collected at Hiroshima Bay, Japan. It was
icosahedral, had a diameter of 34 nm, and accumulated in the nuclei of host
cells. Rod-shaped virus particles also coexisted in the host nuclei. The latent
period and burst size were estimated to be <12 h and 29 infectious units per host
cell, respectively. Csp07DNAV had a closed circular single-stranded DNA genome
(5,552 nucleotides), which included a double-stranded region and 3 open reading
frames. The monophyly of Csp07DNAV and other Bacilladnavirus group single
stranded DNA viruses was supported by phylogenetic analysis that was based on the
amino acid sequence of each virus protein. On the basis of these results, we
considered Csp07DNAV to be a new member of the genus Bacilladnavirus.
PMID- 24358140
TI - Predictions of experimentally observed stochastic ground vibrations induced by
blasting.
AB - In the present paper, we investigate the blast induced ground motion recorded at
the limestone quarry "Suva Vrela" near Kosjeric, which is located in the western
part of Serbia. We examine the recorded signals by means of surrogate data
methods and a determinism test, in order to determine whether the recorded ground
velocity is stochastic or deterministic in nature. Longitudinal, transversal and
the vertical ground motion component are analyzed at three monitoring points that
are located at different distances from the blasting source. The analysis reveals
that the recordings belong to a class of stationary linear stochastic processes
with Gaussian inputs, which could be distorted by a monotonic, instantaneous,
time-independent nonlinear function. Low determinism factors obtained with the
determinism test further confirm the stochastic nature of the recordings. Guided
by the outcome of time series analysis, we propose an improved prediction model
for the peak particle velocity based on a neural network. We show that, while
conventional predictors fail to provide acceptable prediction accuracy, the
neural network model with four main blast parameters as input, namely total
charge, maximum charge per delay, distance from the blasting source to the
measuring point, and hole depth, delivers significantly more accurate predictions
that may be applicable on site. We also perform a sensitivity analysis, which
reveals that the distance from the blasting source has the strongest influence on
the final value of the peak particle velocity. This is in full agreement with
previous observations and theory, thus additionally validating our methodology
and main conclusions.
PMID- 24358141
TI - Intramedullary nail versus dynamic compression plate fixation in treating humeral
shaft fractures: grading the evidence through a meta-analysis.
AB - There is a debate regarding the choice of operative intervention in humeral shaft
fractures that require surgical intervention. The choices for operative
interventions include intramedullary nailing (IMN) and dynamic compression plate
(DCP). This meta-analysis was performed to compare fracture union, functional
outcomes, and complication rates in patients treated with IMN or DCP for humeral
shaft fractures and to develop GRADE (Grading of Recommendations, Assessment,
Development, and Evaluation)-based recommendations for using the procedures to
treat humeral shaft fractures. A systematic search of all the studies published
through December 2012 was conducted using the Medline, Embase, Sciencedirect,
OVID and Cochrane Central databases. The randomized controlled trials (RCTs) and
quasi-RCTs that compared IMN with DCP in treating adult patients with humeral
shaft fractures and provided data regarding the safety and clinical effects were
identified. The demographic characteristics, adverse events and clinical outcomes
were manually extracted from all of the selected studies. Ten studies that
included a total of 448 patients met the inclusion criteria. The results of a
meta-analysis indicated that both IMN and DCP can achieve similar fracture union
with a similar incidence of radial nerve injury and infection. IMN was associated
with an increased risk of shoulder impingement, more restriction of shoulder
movement, an increased risk of intraoperative fracture comminution, a higher
incidence of implant failure, and an increased risk of re-operation. The overall
GRADE system evidence quality was very low, which reduces our confidence in the
recommendations of this system. DCP may be superior to IMN in the treatment of
humeral shaft fractures. Because of the low quality evidence currently available,
high-quality RCTs are required.
PMID- 24358142
TI - Advantageous direct quantification of viable closely related probiotics in petit
suisse cheeses under in vitro gastrointestinal conditions by Propidium Monoazide-
qPCR.
AB - Species-specific Quantitative Real Time PCR (qPCR) alone and combined with the
use of propidium monoazide (PMA) were used along with the plate count method to
evaluate the survival of the probiotic strains Lactobacillus acidophilus La-5 and
Bifidobacterium animalis subsp. lactis Bb-12, and the bacteriocinogenic and
potentially probiotic strain Lactobacillus sakei subsp. sakei 2a in synbiotic
(F1) and probiotic (F2) petit-suisse cheeses exposed throughout shelf-life to in
vitro simulated gastrointestinal tract conditions. The three strains studied
showed a reduction in their viability after the 6 h assay. Bb-12 displayed the
highest survival capacity, above 72.6 and 74.6% of the initial populations,
respectively, by plate count and PMA-qPCR, maintaining population levels in the
range or above 6 log CFU/g. The prebiotic mix of inulin and FOS did not offer any
additional protection for the strains against the simulated gastrointestinal
environment. The microorganisms' populations were comparable among the three
methods at the initial time of the assay, confirming the presence of mainly
viable and culturable cells. However, with the intensification of the stress
induced throughout the various stages of the in vitro test, the differences among
the methods increased. The qPCR was not a reliable enumeration method for the
quantification of intact bacterial populations, mixed with large numbers of
injured and dead bacteria, as confirmed by the scanning electron microscopy
results. Furthermore, bacteria plate counts were much lower (P<0.05) than with
the PMA-qPCR method, suggesting the accumulation of stressed or dead
microorganisms unable to form colonies. The use of PMA overcame the qPCR
inability to differentiate between dead and alive cells. The combination of PMA
and species-specific qPCR in this study allowed a quick and unequivocal way of
enumeration of viable closely related species incorporated into probiotic and
synbiotic petit-suisse cheeses and under stress conditions.
PMID- 24358143
TI - Identification of novel genetic alterations in samples of malignant glioma
patients.
AB - Glioblastoma is the most frequent and malignant human brain tumor. High level of
genomic instability detected in glioma cells implies that numerous genetic
alterations accumulate during glioma pathogenesis. We investigated alterations in
AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11
genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1,
CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations
revealed that 8 genes might play important role in pathogenesis of glial tumors,
while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger
mutations, consequence of high level of genomic instability. Identified genes
have a significant role in signal transduction or cell adhesion, which are
important processes for cancer development and progression. According to our
results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4,
ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic
astrocytoma, suggesting their role in progression of secondary glioblastoma,
while alterations of PDE4D seem to have important role in development of both
glioblastoma subtypes. Some of the identified genes showed significant
association with p53, p16, and EGFR, but there was no significant correlation
between loss of PTEN and any of identified genes. In conclusion our study
revealed genetic alterations that were not previously associated with glioma
pathogenesis and could be potentially used as molecular markers of different
glioblastoma subtypes.
PMID- 24358144
TI - Deep sequencing-based transcriptional analysis of bovine mammary epithelial cells
gene expression in response to in vitro infection with Staphylococcus aureus
stains.
AB - Staphylococcus aureus (S. aureus) is an important etiological organism in chronic
and subclinical mastitis in lactating cows. Given the fundamental role the
primary bovine mammary epithelial cells (pBMECs) play as a major first line of
defense against invading pathogens, their interactions with S. aureus was
hypothesized to be crucial to the establishment of the latter's infection
process. This hypothesis was tested by investigating the global transcriptional
responses of pBMECs to three S. aureus strains (S56,S178 and S36) with different
virulent factors, using a tag-based high-throughput transcriptome sequencing
technique. Approximately 4.9 million total sequence tags were obtained from each
of the three S. aureus-infected libraries and the control library. Referenced to
the control, 1720, 219, and 427 differentially expressed unique genes were
identified in the pBMECs infected with S56, S178 and S36 S. aureus strains
respectively. Gene ontology (GO) and pathway analysis of the S56-infected pBMECs
referenced to those of the control revealed that the differentially expressed
genes in S56-infected pBMECs were significantly involved in inflammatory
response, cell signalling pathways and apoptosis. In the same vein, the clustered
GO terms of the differentially expressed genes of the S178-infected pBMECs were
found to comprise immune responses, metabolism transformation, and apoptosis,
while those of the S36-infected pBMECs were primarily involved in cell cycle
progression and immune responses. Furthermore, fundamental differences were
observed in the levels of expression of immune-related genes in response to
treatments with the three S. aureus strains. These differences were especially
noted for the expression of important pro-inflammatory molecules, including IL
1alpha, TNF, EFNB1, IL-8, and EGR1. The transcriptional changes associated with
cellular signaling and the inflammatory response in this study may reflect
different immunomodulatory mechanisms that underlie the interaction between
pBMECs and S. aureus strains during infection by the latter.
PMID- 24358145
TI - Does serum 25-hydroxyvitamin D influence muscle development during puberty in
girls? A 7-year longitudinal study.
AB - Vitamin D is well known for its regulatory role in calcium and phosphate
homeostasis, but its role in muscle mass and strength during growth remains
inconclusive. We explored the association of serum 25-hydroxyvitamin D (25(OH)D)
with muscle development in girls from 11 to 18-years old. Whole body lean tissue
mass (LMWB), appendicular lean mass (aLM), muscle cross-sectional area at the
lower leg (mCSA), maximal voluntary contraction of elbow flexors (MVC elbow) and
knee extensors (MVC knee) were assessed in 217 girls aged 10-13 years (at
baseline), 215 in 2-year and 226 in 7.5-year follow-up. Serum concentration of
25(OH)D and intact parathyroid hormone (PTH) were analyzed retrospectively and
girls were categorized according to their 25(OH)D levels (consistently
insufficient 25(OH)D GLL <50 nmol/l and consistently sufficient GHH >50 nmol/l
from baseline to 7-year follow-up). We found that 25(OH)D level declined until
menarche (p<0.05) while LMWB, aLM, mCSA, MVC elbow and MVC knee continued to
increase (p<0.001 for all) post menarche. At pre-menarche, the GLL (n = 34) had
higher LMWB and aLM than the GHH (n = 21, p<0.05), while post-menarche the GHH (n
= 15) had a greater catch-up gain in LMWB (p = 0.004), aLM (p = 0.001) and mCSA
(p = 0.027) compared to the GLL (n = 65) over the first 2-year period. At the age
of 18, no differences in muscle mass/strength between the low (n = 151) and high
(n = 77) levels of 25(OH)D groups were found. This finding was independent of
vitamin D receptor genotype and other confounders. In conclusion, our results
showed that levels of 25(OH)D have no significant negative influence on the
development of muscle mass and strength during pubertal growth both with
longitudinal and cross-sectional comparison. On the contrary, our results suggest
that the temporary negative association between 25(OH)D and muscle mass arises as
a consequence of fast growth prior to menarche, and this negative association is
diminished through catch-up growth after menarche.
PMID- 24358146
TI - Comparative transcriptome analysis of two rice varieties in response to rice
stripe virus and small brown planthoppers during early interaction.
AB - Rice stripe, a virus disease, transmitted by a small brown planthopper (SBPH),
has greatly reduced production of japonica rice in East Asia, especially in
China. Although we have made great progress in mapping resistance genes, little
is known about the mechanism of resistance. By de novo transcriptome assembling,
we gained sufficient transcript data to analyze changes in gene expression of
early interaction in response to SBPH and RSV infection in rice. Respectively 648
and 937 DEGs were detected from the disease-resistant (Liaonong 979) and the
susceptible (Fengjin) varieties, most of which were up-regulated. We found 37
genes related to insect resistance, which mainly included genes for jasmonate
induced protein, TIFY protein, lipoxygenase, as well as trypsin inhibitor genes
and transcription factor genes. In the interaction process between RSV and rice,
87 genes were thought to be related to RSV resistance; these primarily included
12 peroxidase biosynthesis genes, 12 LRR receptor-like protein kinase genes, 6
genes coding pathogenesis-related proteins, 4 glycine-rich cell wall structural
protein genes, 2 xyloglucan hydrolase genes and a cellulose synthase. The results
indicate that the rice-pathogen interaction happened both in disease-resistant
and susceptible varieties, and some genes related to JA biosynthesis played key
roles in the interaction between SBPHs and rice. When rice was infected by RSV a
hypersensitive reaction (HR) in the disease-resistant variety was suppressed,
which resulted from an increase in peroxidase expression and down-regulation of
LRR receptor-like protein kinase and pathogenesis-related proteins, while, the
changes of peroxidase biosynthesis, glycine-rich cell wall structural protein,
cellulose synthase and xyloglucan endotransglucosylase/hydrolase could lead to
the strengthening of physical barriers of rice, which may be an important
resistance mechanism to RSV in rice.
PMID- 24358147
TI - Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric
cancer.
AB - BACKGROUND: NPM, TFF3 and TACC1 are molecular markers that play important roles
in cell differentiation. Herein, we investigated their prognostic impact in
patients with primary gastric cancer (GC) and determined whether they could be
used as markers of more aggressive gastric carcinomas by detecting the extent of
expression in human gastric carcinoma samples. METHODOLOGY/PRINCIPAL FINDINGS:
Tumor tissue specimens from 142 GC patients were retrospectively retrieved and
immunohistochemically evaluated. Correlations between NPM, TFF3 and TACC1 over
expression and clinicopathologic parameters, and their prognostic values were
investigated with chi(2), Kaplan-Meier method, and Cox uni- and multivariate
survival models. NPM, TFF3 and TACC1 expression was significantly higher in GC
patients with poorly differentiated histologic type than that in patients with
well differentiated histologic type. NPM expression was significantly higher in
patients with hepatic metastasis or recurrence than that in patients without
metastasis. TFF3 expression was significantly higher in patients with positive
lymph node metastasis than that in patients with negative lymph node metastasis.
Age, lymph node metastasis, and TFF3 and TACC1 over-expression were significantly
correlated with low survival (P<0.05, P<0.05, P = 0.005 and P = 0.009,
respectively). Multivariate analysis showed that lymph node metastasis and TFF3
and TACC1 over-expression were independent prognostic factors. CONCLUSIONS: TFF3
and TACC1 over-expression in epithelial cells of surgically resected GC tissues
was an independent predictor of short survival in GC patients. The prognosis was
poorer in patients with positive expression of both TFF3 and TACC1 than that in
patients with positive expression of TFF3 or TACC1 alone, or with negative
expression of TFF3 and TACC1.
PMID- 24358148
TI - Low-rank regularization for learning gene expression programs.
AB - Learning gene expression programs directly from a set of observations is
challenging due to the complexity of gene regulation, high noise of experimental
measurements, and insufficient number of experimental measurements. Imposing
additional constraints with strong and biologically motivated regularizations is
critical in developing reliable and effective algorithms for inferring gene
expression programs. Here we propose a new form of regulation that constrains the
number of independent connectivity patterns between regulators and targets,
motivated by the modular design of gene regulatory programs and the belief that
the total number of independent regulatory modules should be small. We formulate
a multi-target linear regression framework to incorporate this type of
regulation, in which the number of independent connectivity patterns is expressed
as the rank of the connectivity matrix between regulators and targets. We then
generalize the linear framework to nonlinear cases, and prove that the
generalized low-rank regularization model is still convex. Efficient algorithms
are derived to solve both the linear and nonlinear low-rank regularized problems.
Finally, we test the algorithms on three gene expression datasets, and show that
the low-rank regularization improves the accuracy of gene expression prediction
in these three datasets.
PMID- 24358149
TI - Identification of common blood gene signatures for the diagnosis of renal and
cardiac acute allograft rejection.
AB - To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are
able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood
samples from heart transplant recipients with and without acute rejection (AR)
and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic
regression model was built on 5 of these 10 genes (AR threshold composite score
>37% = AR) and tested for AR prediction in an independent set of 109 samples,
where it correctly diagnosed AR with 89% accuracy, with no misclassifications for
AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes
correctly diagnosed AR in a blood sample within 6 months prior to biopsy
diagnosis with 80% sensitivity and untreated grade 1b AR episodes had
persistently elevated scores until 6 months after biopsy diagnosis. The gene
score was also correlated with presence or absence of cardiac allograft
vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a
common transcriptional axis of immunological trafficking in peripheral blood in
both renal and cardiac organ transplant rejection, across a diverse recipient age
range. A common gene signature, initially identified in the setting of renal
transplant rejection, can be utilized serially after cardiac transplantation, to
diagnose and predict biopsy confirmed acute heart transplant rejection.
PMID- 24358150
TI - A novel null homozygous mutation confirms CACNA2D2 as a gene mutated in epileptic
encephalopathy.
AB - Contribution to epileptic encephalopathy (EE) of mutations in CACNA2D2, encoding
alpha2delta-2 subunit of Voltage Dependent Calcium Channels, is unclear. To date
only one CACNA2D2 mutation altering channel functionality has been identified in
a single family. In the same family, a rare CELSR3 polymorphism also segregated
with disease. Involvement of CACNA2D2 in EE is therefore not confirmed, while
that of CELSR3 is questionable. In a patient with epilepsy, dyskinesia,
cerebellar atrophy, psychomotor delay and dysmorphic features, offspring to
consanguineous parents, we performed whole exome sequencing (WES) for
homozygosity mapping and mutation detection. WES identified extended autozygosity
on chromosome 3, containing two novel homozygous candidate mutations: c.1295delA
(p.Asn432fs) in CACNA2D2 and c.G6407A (p.Gly2136Asp) in CELSR3. Gene
prioritization pointed to CACNA2D2 as the most prominent candidate gene. The WES
finding in CACNA2D2 resulted to be statistically significant (p = 0.032), unlike
that in CELSR3. CACNA2D2 homozygous c.1295delA essentially abolished alpha2delta
2 expression. In summary, we identified a novel null CACNA2D2 mutation associated
to a clinical phenotype strikingly similar to the Cacna2d2 null mouse model.
Molecular and statistical analyses together argued in favor of a causal
contribution of CACNA2D2 mutations to EE, while suggested that finding in CELSR3,
although potentially damaging, is likely incidental.
PMID- 24358151
TI - Systemic compensatory response to neonatal estradiol exposure does not prevent
depletion of the oocyte pool in the rat.
AB - The formation of ovarian follicles is a finely tuned process that takes place
within a narrow time-window in rodents. Multiple factors and pathways have been
proposed to contribute to the mechanisms triggering this process but the role of
endocrine factors, especially estrogens, remains elusive. It is currently
hypothesized that removal from the maternal hormonal environment permits follicle
formation at birth. However, experimentally-induced maintenance of high 17beta
estradiol (E2) levels leads to subtle, distinct, immediate effects on follicle
formation and oocyte survival depending on the species and dose. In this study,
we examined the immediate effects of neonatal E2 exposure from post-natal day
(PND) 0 to PND2 on the whole organism and on ovarian follicle formation in rats.
Measurements of plasma E2, estrone and their sulfate conjugates after E2 exposure
showed that neonatal female rats rapidly acquire the capability to metabolize and
clear excessive E2 levels. Concomitant modifications to the mRNA content of genes
encoding selected E2 metabolism enzymes in the liver and the ovary in response to
E2 exposure indicate that E2 may modify the neonatal maturation of these organs.
In the liver, E2 treatment was associated with lower acquisition of the
capability to metabolize E2. In the ovary, E2 depleted the oocyte pool in a dose
dependent manner by PND3. In 10 ug/day E2-treated ovaries, apoptotic oocytes were
observed in newly formed follicles in addition to areas of ovarian cord
remodeling. At PND6, follicles without any visible oocyte were present and multi
oocyte follicles were not observed. Our study reveals a major species-difference.
Indeed, neonatal exposure to E2 depletes the oocyte pool in the rat ovary,
whereas in the mouse it is well known to increase oocyte survival.
PMID- 24358154
TI - Translational science by public biotechnology companies in the IPO "class of
2000": the impact of technological maturity.
AB - The biotechnology industry plays a central role in the translation of nascent
biomedical science into both products that offer material health benefits and
creating capital growth. This study examines the relationship between the
maturity of technologies in a characteristic life cycle and value creation by
biotechnology companies. We examined the core technology, product development
pipelines, and capitalization for a cohort of biotechnology companies that
completed an IPO in 2000. Each of these companies was well financed and had core
technologies on the leading edge of biological science. We found that companies
with the least mature technologies had significantly higher valuations at IPO,
but failed to develop products based on these technologies over the ensuing
decade, and created less capital growth than companies with more mature
technologies at IPO. The observation that this cohort of recently public
biotechnology companies was not effective in creating value from nascent science
suggests the need for new, evidence-based business strategies for translational
science.
PMID- 24358153
TI - Role of 5-HTTLPR polymorphism in the development of the inward/outward
personality organization: a genetic association study.
AB - Reciprocity with primary caregivers affects subjects' adaptive abilities toward
the construction of the most useful personal meaning organization (PMO) with
respect to their developmental environment. Within cognitive theory the post
rationalist approach has outlined two basic categories of identity construction
and of regulation of cognitive and emotional processes: the Outward and the
Inward PMO. The presence of different, consistent clinical patterns in Inward and
Outward subjects is paralleled by differences in cerebral activation during
emotional tasks on fMRI and by different expression of some polymorphisms in
serotonin pathways. Since several lines of evidence support a role for the 5
HTTLPR polymorphism in mediating individual susceptibility to environmental
emotional stimuli, this study was conducted to investigate its influence in the
development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR
polymorphism investigated in 124 healthy subjects who were subdivided into an
Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short
allele (S) frequencies showed significant differences between Inwards and
Outwards (p = 0.036, chi2 test; p = 0.026, exact test). Genotype frequencies were
not significantly different although values slightly exceeded p <= 0.05 (p =
0.056, chi2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes
according to the recessive inheritance model showed that the S/S genotype
increased the likelihood of developing an Outward PMO (p = 0.0178, chi2 test; p =
0.0143, exact test; OR = 3.43, CI (95%) = 1.188-9.925). A logistic regression
analysis confirmed the association between short allele and S/S genotypes with
the Outward PMO also when gender and age were considered. However none of the
differences remained significant after correction for multiple testing, even
though using the recessive model they approach significance. Overall our data
seem to suggest a putative genetic basis for interindividual differences in PMO
development.
PMID- 24358152
TI - A conserved sequence extending motif III of the motor domain in the Snf2-family
DNA translocase Rad54 is critical for ATPase activity.
AB - Rad54 is a dsDNA-dependent ATPase that translocates on duplex DNA. Its ATPase
function is essential for homologous recombination, a pathway critical for
meiotic chromosome segregation, repair of complex DNA damage, and recovery of
stalled or broken replication forks. In recombination, Rad54 cooperates with
Rad51 protein and is required to dissociate Rad51 from heteroduplex DNA to allow
access by DNA polymerases for recombination-associated DNA synthesis. Sequence
analysis revealed that Rad54 contains a perfect match to the consensus PIP box
sequence, a widely spread PCNA interaction motif. Indeed, Rad54 interacts
directly with PCNA, but this interaction is not mediated by the Rad54 PIP box
like sequence. This sequence is located as an extension of motif III of the Rad54
motor domain and is essential for full Rad54 ATPase activity. Mutations in this
motif render Rad54 non-functional in vivo and severely compromise its activities
in vitro. Further analysis demonstrated that such mutations affect dsDNA binding,
consistent with the location of this sequence motif on the surface of the cleft
formed by two RecA-like domains, which likely forms the dsDNA binding site of
Rad54. Our study identified a novel sequence motif critical for Rad54 function
and showed that even perfect matches to the PIP box consensus may not necessarily
identify PCNA interaction sites.
PMID- 24358155
TI - Trophic relationships and habitat preferences of delphinids from the southeastern
Brazilian coast determined by carbon and nitrogen stable isotope composition.
AB - To investigate the foraging habitats of delphinids in southeastern Brazil, we
analyzed stable carbon (delta(13)C) and nitrogen (delta(15)N) isotopes in muscle
samples of the following 10 delphinid species: Sotalia guianensis, Stenella
frontalis, Tursiops truncatus, Steno bredanensis, Pseudorca crassidens, Delphinus
sp., Lagenodelphis hosei, Stenella attenuata, Stenella longirostris and Grampus
griseus. We also compared the delta(13)C and delta(15)N values among four
populations of S. guianensis. Variation in carbon isotope results from coast to
ocean indicated that there was a significant decrease in delta(13)C values from
estuarine dolphins to oceanic species. S. guianensis from Guanabara Bay had the
highest mean delta(13)C value, while oceanic species showed significantly lower
delta(13)C values. The highest delta(15)N values were observed for P. crassidens
and T. truncatus, suggesting that these species occupy the highest trophic
position among the delphinids studied here. The oceanic species S. attenuata, G.
griseus and L. hosei had the lowest delta(15)N values. Stable isotope analysis
showed that the three populations of S. guianensis in coastal bays had different
delta(13)C values, but similar delta(15)N results. Guiana dolphins from Sepetiba
and Ilha Grande bays had different foraging habitat, with specimens from Ilha
Grande showing more negative delta(13)C values. This study provides further
information on the feeding ecology of delphinids occurring in southeastern
Brazil, with evidence of distinctive foraging habitats and the occupation of
different ecological niches by these species in the study area.
PMID- 24358156
TI - A model to discriminate malignant from benign thyroid nodules using artificial
neural network.
AB - OBJECTIVE: This study aimed to construct a model for using in differentiating
benign and malignant nodules with the artificial neural network and to increase
the objective diagnostic accuracy of US. MATERIALS AND METHODS: 618 consecutive
patients (528 women, 161 men) with 689 thyroid nodules (425 malignant and 264
benign nodules) were enrolled in the present study. The presence and absence of
each sonographic feature was assessed for each nodule - shape, margin,
echogenicity, internal composition, presence of calcifications, peripheral halo
and vascularity on color Doppler. The variables meet the following criteria:
important sonographic features and statistically significant difference were
selected as the input layer to build the ANN for predicting the malignancy of
nodules. RESULTS: Six sonographic features including shape (Taller than wide,
p<0.001), margin (Not Well-circumscribed, p<0.001), echogenicity
(Hypoechogenicity, p<0.001), internal composition (Solid, p<0.001), presence of
calcifications (Microcalcification, p<0.001) and peripheral halo (Absent,
p<0.001) were significantly associated with malignant nodules. A three-layer 6-8
1 feed-forward ANN model was built. In the training cohort, the accuracy of the
ANN in predicting malignancy of thyroid nodules was 82.3% (AURO = 0.818), the
sensitivity and specificity was 84.5% and 79.1%, respectively. In the validation
cohort, the accuracy, sensitivity and specificity was 83.1%, 83.8% and 81.8%,
respectively. The AUROC was 0.828. CONCLUSION: ANN constructed by sonographic
features can discriminate benign and malignant thyroid nodules with high
diagnostic accuracy.
PMID- 24358157
TI - A distinct and divergent lineage of genomic island-associated Type IV Secretion
Systems in Legionella.
AB - Legionella encodes multiple classes of Type IV Secretion Systems (T4SSs),
including the Dot/Icm protein secretion system that is essential for
intracellular multiplication in amoebal and human hosts. Other T4SSs not
essential for virulence are thought to facilitate the acquisition of niche
specific adaptation genes including the numerous effector genes that are a
hallmark of this genus. Previously, we identified two novel gene clusters in the
draft genome of Legionella pneumophila strain 130b that encode homologues of a
subtype of T4SS, the genomic island-associated T4SS (GI-T4SS), usually associated
with integrative and conjugative elements (ICE). In this study, we performed
genomic analyses of 14 homologous GI-T4SS clusters found in eight publicly
available Legionella genomes and show that this cluster is unusually well
conserved in a region of high plasticity. Phylogenetic analyses show that
Legionella GI-T4SSs are substantially divergent from other members of this
subtype of T4SS and represent a novel clade of GI-T4SSs only found in this genus.
The GI-T4SS was found to be under purifying selection, suggesting it is
functional and may play an important role in the evolution and adaptation of
Legionella. Like other GI-T4SSs, the Legionella clusters are also associated with
ICEs, but lack the typical integration and replication modules of related ICEs.
The absence of complete replication and DNA pre-processing modules, together with
the presence of Legionella-specific regulatory elements, suggest the Legionella
GI-T4SS-associated ICE is unique and may employ novel mechanisms of regulation,
maintenance and excision. The Legionella GI-T4SS cluster was found to be
associated with several cargo genes, including numerous antibiotic resistance and
virulence factors, which may confer a fitness benefit to the organism. The in
silico characterisation of this new T4SS furthers our understanding of the
diversity of secretion systems involved in the frequent horizontal gene transfers
that allow Legionella to adapt to and exploit diverse environmental niches.
PMID- 24358158
TI - Adelie penguin population diet monitoring by analysis of food DNA in scats.
AB - The Adelie penguin is the most important animal currently used for ecosystem
monitoring in the Southern Ocean. The diet of this species is generally studied
by visual analysis of stomach contents; or ratios of isotopes of carbon and
nitrogen incorporated into the penguin from its food. There are significant
limitations to the information that can be gained from these methods. We
evaluated population diet assessment by analysis of food DNA in scats as an
alternative method for ecosystem monitoring with Adelie penguins as an indicator
species. Scats were collected at four locations, three phases of the breeding
cycle, and in four different years. A novel molecular diet assay and
bioinformatics pipeline based on nuclear small subunit ribosomal RNA gene (SSU
rDNA) sequencing was used to identify prey DNA in 389 scats. Analysis of the
twelve population sample sets identified spatial and temporal dietary change in
Adelie penguin population diet. Prey diversity was found to be greater than
previously thought. Krill, fish, copepods and amphipods were the most important
food groups, in general agreement with other Adelie penguin dietary studies based
on hard part or stable isotope analysis. However, our DNA analysis estimated that
a substantial portion of the diet was gelatinous groups such as jellyfish and
comb jellies. A range of other prey not previously identified in the diet of this
species were also discovered. The diverse prey identified by this DNA-based scat
analysis confirms that the generalist feeding of Adelie penguins makes them a
useful indicator species for prey community composition in the coastal zone of
the Southern Ocean. Scat collection is a simple and non-invasive field sampling
method that allows DNA-based estimation of prey community differences at many
temporal and spatial scales and provides significant advantages over alternative
diet analysis approaches.
PMID- 24358160
TI - Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts.
AB - Odontoblasts produce dentin during development, throughout life, and in response
to pathological conditions by sensing stimulation of exposed dentin. The
functional properties and localization patterns of transient receptor potential
(TRP) melastatin subfamily member 8 (TRPM8) and ankyrin subfamily member 1
(TRPA1) channels in odontoblasts remain to be clarified. We investigated the
localization and the pharmacological, biophysical, and mechano-sensitive
properties of TRPM8 and TRPA1 channels in rat odontoblasts. Menthol and icilin
increased the intracellular free Ca(2+) concentration ([Ca(2+)]i). Icilin-, WS3-,
or WS12-induced [Ca(2+)]i increases were inhibited by capsazepine or 5
benzyloxytriptamine. The increase in [Ca(2+)]i elicited by allyl isothiocyanate
(AITC) was inhibited by HC030031. WS12 and AITC exerted a desensitizing effect on
[Ca(2+)]i increase. Low-temperature stimuli elicited [Ca(2+)]i increases that are
sensitive to both 5-benzyloxytriptamine and HC030031. Hypotonic stimulation
induced membrane stretch increased [Ca(2+)]i; HC030031 but not 5
benzyloxytriptamine inhibited the effect. The results suggest that TRPM8 channels
in rat odontoblasts play a role in detecting low-temperature stimulation of the
dentin surface and that TRPA1 channels are involved in sensing membrane
stretching and low-temperature stimulation. The results also indicate that
odontoblasts act as mechanical and thermal receptor cells, detecting the
stimulation of exposed dentin to drive multiple cellular functions, such as
sensory transduction.
PMID- 24358161
TI - On the encoding of proteins for disordered regions prediction.
AB - Disordered regions, i.e., regions of proteins that do not adopt a stable three
dimensional structure, have been shown to play various and critical roles in many
biological processes. Predicting and understanding their formation is therefore a
key sub-problem of protein structure and function inference. A wide range of
machine learning approaches have been developed to automatically predict
disordered regions of proteins. One key factor of the success of these methods is
the way in which protein information is encoded into features. Recently, we have
proposed a systematic methodology to study the relevance of various feature
encodings in the context of disulfide connectivity pattern prediction. In the
present paper, we adapt this methodology to the problem of predicting disordered
regions and assess it on proteins from the 10th CASP competition, as well as on a
very large subset of proteins extracted from PDB. Our results, obtained with
ensembles of extremely randomized trees, highlight a novel feature function
encoding the proximity of residues according to their accessibility to the
solvent, which is playing the second most important role in the prediction of
disordered regions, just after evolutionary information. Furthermore, even though
our approach treats each residue independently, our results are very competitive
in terms of accuracy with respect to the state-of-the-art. A web-application is
available at http://m24.giga.ulg.ac.be:81/x3Disorder.
PMID- 24358159
TI - Preventive effect of halofuginone on concanavalin A-induced liver fibrosis.
AB - Halofuginone (HF) is an active component of extracts derived from the plant
alkaloid febrifugine and has shown therapeutic promise in animal models of
fibrotic disease. Our main objectives were to clarify the suppressive effect of
HF on concanavalin A (ConA)-induced liver fibrosis. ConA injection into the tail
vein caused a great increase in the serum aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) levels, while orally administration of HF
significantly decreased the levels of the transaminases. In addition, the levels
of hyaluronic acid (HA), procollagen III (PCIII) and TGF-beta1 in the serum and
collagen I, alpha-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2) and Smad3
in the liver tissue were significantly lowered with the treatment of HF.
Histological examination also demonstrated that HF significantly reduced the
severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the
repeated activation of T cells, immunomodulatory substances might be responsible
for the suppressive effect of HF. We found that the production of nuclear factor
(NF)-kB in the serum was increased in ConA-treated group, while decreased
significantly with the treatment of HF. The changes of inflammatory cytokines
tumor necrosis factor (TNF-alpha), IL-6 and IL-1beta in the serum followed the
same rhythm. All together, our findings indicate that orally administration HF
(10ppm) would attenuate the liver fibrosis by suppressing the synthesis of
collagen I and inflammation-mediated liver injury.
PMID- 24358162
TI - Evaluation of New Zealand's high-seas bottom trawl closures using predictive
habitat models and quantitative risk assessment.
AB - United Nations General Assembly Resolution 61/105 on sustainable fisheries (UNGA
2007) establishes three difficult questions for participants in high-seas bottom
fisheries to answer: 1) Where are vulnerable marine systems (VMEs) likely to
occur?; 2) What is the likelihood of fisheries interaction with these VMEs?; and
3) What might qualify as adequate conservation and management measures to prevent
significant adverse impacts? This paper develops an approach to answering these
questions for bottom trawling activities in the Convention Area of the South
Pacific Regional Fisheries Management Organisation (SPRFMO) within a quantitative
risk assessment and cost : benefit analysis framework. The predicted distribution
of deep-sea corals from habitat suitability models is used to answer the first
question. Distribution of historical bottom trawl effort is used to answer the
second, with estimates of seabed areas swept by bottom trawlers being used to
develop discounting factors for reduced biodiversity in previously fished areas.
These are used in a quantitative ecological risk assessment approach to guide
spatial protection planning to address the third question. The coral VME
likelihood (average, discounted, predicted coral habitat suitability) of existing
spatial closures implemented by New Zealand within the SPRFMO area is evaluated.
Historical catch is used as a measure of cost to industry in a cost : benefit
analysis of alternative spatial closure scenarios. Results indicate that current
closures within the New Zealand SPRFMO area bottom trawl footprint are suboptimal
for protection of VMEs. Examples of alternative trawl closure scenarios are
provided to illustrate how the approach could be used to optimise protection of
VMEs under chosen management objectives, balancing protection of VMEs against
economic loss to commercial fishers from closure of historically fished areas.
PMID- 24358163
TI - Invasive and non-invasive congeners show similar trait shifts between their same
native and non-native ranges.
AB - Differences in morphological or ecological traits expressed by exotic species
between their native and non-native ranges are often interpreted as evidence for
adaptation to new conditions in the non-native ranges. In turn this adaptation is
often hypothesized to contribute to the successful invasion of these species.
There is good evidence for rapid evolution by many exotic invasives, but the
extent to which these evolutionary changes actually drive invasiveness is
unclear. One approach to resolving the relationship between adaptive responses
and successful invasion is to compare traits between populations from the native
and non-native ranges for both exotic invaders and congeners that are exotic but
not invasive. We compared a suite of morphological traits that are commonly
tested in the literature in the context of invasion for three very closely
related species of Centaurea, all of which are sympatric in the same native and
non-native ranges in Europe and North America. Of these, C. solstitialis is
highly invasive whereas C. calcitrapa and C. sulphurea are not. For all three
species, plants from non-native populations showed similar shifts in key traits
that have been identified in other studies as important putative adaptive
responses to post-introduction invasion. For example, for all three species
plants from populations in non-native ranges were (i) larger and (ii) produced
seeds that germinated at higher rates. In fact, the non-invasive C. calcitrapa
showed the strongest trait shift between ranges. Centaurea solstitialis was the
only species for which plants from the non-native range increased allocation to
defensive spines, and allocated proportionally less resources to reproduction,
patterns contrary to what would be predicted by theory and other empirical
studies to enhance invasion. Our results suggest caution when interpreting the
commonly observed increase in size and reproductive capacity as factors that
cause exotics to become invaders.
PMID- 24358164
TI - Identification of crucial amino acids in mouse aldehyde oxidase 3 that determine
substrate specificity.
AB - In order to elucidate factors that determine substrate specificity and activity
of mammalian molybdo-flavoproteins we performed site directed mutagenesis of
mouse aldehyde oxidase 3 (mAOX3). The sequence alignment of different aldehyde
oxidase (AOX) isoforms identified variations in the active site of mAOX3 in
comparison to other AOX proteins and xanthine oxidoreductases (XOR). Based on the
structural alignment of mAOX3 and bovine XOR, differences in amino acid residues
involved in substrate binding in XORs in comparison to AOXs were identified. We
exchanged several residues in the active site to the ones found in other AOX
homologues in mouse or to residues present in bovine XOR in order to examine
their influence on substrate selectivity and catalytic activity. Additionally we
analyzed the influence of the [2Fe-2S] domains of mAOX3 on its kinetic properties
and cofactor saturation. We applied UV-VIS and EPR monitored redox-titrations to
determine the redox potentials of wild type mAOX3 and mAOX3 variants containing
the iron-sulfur centers of mAOX1. In addition, a combination of molecular docking
and molecular dynamic simulations (MD) was used to investigate factors that
modulate the substrate specificity and activity of wild type and AOX variants.
The successful conversion of an AOX enzyme to an XOR enzyme was achieved
exchanging eight residues in the active site of mAOX3. It was observed that the
absence of the K889H exchange substantially decreased the activity of the enzyme
towards all substrates analyzed, revealing that this residue has an important
role in catalysis.
PMID- 24358165
TI - Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle
arrest in vivo and in vitro.
AB - Nasopharyngeal carcinoma is a common malignant tumor in the head and neck.
Because of frequent recurrence and distant metastasis which are the main causes
of death, better treatment is needed. Indole-3-carbinol (I3C), a natural
phytochemical found in the vegetables of the cruciferous family, shows anticancer
effect through various signal pathways. I3C induces G1 arrest in NPC cell line
with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1
and pRb. In vivo, nude mice receiving I3C protectively or therapeutically
exhibited smaller tumors than control group after they were inoculated with
nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb
in preventive treatment group and drug treatment group both decreased compared
with the control group. We conclude that I3C can inhibit the growth of NPC in
vitro and in vivo by suppressing the expression of CDK and cyclin families. The
drug was safe and had no toxic effects on normal tissues and organs.
PMID- 24358166
TI - An antioxidant extract of tropical lichen, Parmotrema reticulatum, induces cell
cycle arrest and apoptosis in breast carcinoma cell line MCF-7.
AB - This report highlights the phytochemical analysis, antioxidant potential and
anticancer activity against breast carcinoma of 70% methanolic extract of lichen,
Parmotrema reticulatum (PRME). Phytochemical analysis of PRME confirms the
presence of various phytoconstituents like alkaloids, carbohydrates, flavonoids,
glycosides, phenols, saponins, tannins, anthraquinones, and ascorbic acid; among
which alkaloids, phenols and flavonoids are found in abundant amount. High
performance liquid chromatography (HPLC) analysis of PRME revealed the presence
of catechin, purpurin, tannic acid and reserpine. Antioxidant activity was
evaluated by nine separate methods. PRME showed excellent hydroxyl and
hypochlorous radical scavenging as well as moderate DPPH, superoxide, singlet
oxygen, nitric oxide and peroxynitrite scavenging activity. Cytotoxicity of PRME
was tested against breast carcinoma (MCF-7), lung carcinoma (A549) and normal
lung fibroblast (WI-38) using WST-1 method. PRME was found cytotoxic against MCF
7 cells with an IC50 value 130.03 +/- 3.11 ug/ml while negligible cytotoxicity
was observed on A549 and WI-38 cells. Further flow cytometric study showed that
PRME halted the MCF-7 cells in S and G2/M phases and induces apoptosis in dose as
well as time dependent manner. Cell cycle arrest was associated with
downregulation of cyclin B1, Cdk-2 and Cdc25C as well as slight decrease in the
expression of Cdk-1 and cyclin A1 with subsequent upregulation of p53 and p21.
Moreover PRME induced Bax and inhibited Bcl-2 expression, which results in
increasing Bax/Bcl-2 ratio and activation of caspase cascade. This ultimately
leads to PARP degradation and induces apoptosis in MCF-7 cells. It can be
hypothesised from the current study that the antioxidant and anticancer potential
of the PRME may reside in the phytoconstitutents present in it and therefore,
PRME may be used as a possible source of natural antioxidant that may be
developed to an anticancer agent.
PMID- 24358167
TI - Tryptanthrin inhibits angiogenesis by targeting the VEGFR2-mediated ERK1/2
signalling pathway.
AB - Angiogenesis is a key step for tumour growth and metastasis, and anti
angiogenesis has been proposed as an important strategy for cancer therapy.
Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of
medicinal indigo plants and has been shown to possess anti-tumour activities on
various cancer cell types. This study aims to investigate the in vitro and in
vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying
molecular action mechanisms. Our results show that tryptanthrin inhibited the in
vitro proliferation, migration, and tube formation of the human microvascular
endothelial cells (HMEC-1) in a concentration-dependent manner and significantly
suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated
that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang
1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated
ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation
indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2.
Collectively, the present study demonstrated that tryptanthrin exhibited both in
vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated
ERK1/2 signalling pathway and might have therapeutic potential for the treatment
of angiogenesis-related diseases.
PMID- 24358168
TI - Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of
hepatitis C virus.
AB - Caffeic acid phenethyl ester (CAPE) has been reported as a multifunctional
compound. In this report, we tested the effect of CAPE and its derivatives on
hepatitis C virus (HCV) replication in order to develop an effective anti-HCV
compound. CAPE and CAPE derivatives exhibited anti-HCV activity against an HCV
replicon cell line of genotype 1b with EC50 values in a range from 1.0 to 109.6
uM. Analyses of chemical structure and antiviral activity suggested that the
length of the n-alkyl side chain and catechol moiety are responsible for the anti
HCV activity of these compounds. Caffeic acid n-octyl ester exhibited the highest
anti-HCV activity among the tested derivatives with an EC50 value of 1.0 uM and
an SI value of 63.1 by using the replicon cell line derived from genotype 1b
strain Con1. Treatment with caffeic acid n-octyl ester inhibited HCV replication
of genotype 2a at a similar level to that of genotype 1b irrespectively of
interferon signaling. Caffeic acid n-octyl ester could synergistically enhance
the anti-HCV activities of interferon-alpha 2b, daclatasvir, and VX-222, but
neither telaprevir nor danoprevir. These results suggest that caffeic acid n
octyl ester is a potential candidate for novel anti-HCV chemotherapy drugs.
PMID- 24358169
TI - Soluble beta-amyloid Precursor Protein Alpha binds to p75 neurotrophin receptor
to promote neurite outgrowth.
AB - BACKGROUND: The cleavage of beta-amyloid precursor protein (APP) generates
multiple proteins: Soluble beta-amyloid Precursor Protein Alpha (sAPPalpha),
sAPPbeta, and amyloid beta (Abeta). Previous studies have shown that sAPPalpha
and sAPPbeta possess neurotrophic properties, whereas Abeta is neurotoxic.
However, the underlying mechanism of the opposing effects of APP fragments
remains poorly understood. In this study, we have investigated the mechanism of
sAPPalpha-mediated neurotrophic effects. sAPPalpha and sAPPbeta interact with p75
neurotrophin receptor (p75(NTR)), and sAPPalpha promotes neurite outgrowth.
METHODS AND FINDINGS: First, we investigated whether APP fragments interact with
p75(NTR), because full-length APP and Abeta have been shown to interact with
p75(NTR) in vitro. Both sAPPalpha and sAPPbeta were co-immunoprecipitated with
p75(NTR) and co-localized with p75(NTR) on COS-7 cells. The binding affinity of
sAPPalpha and sAPPbeta for p75(NTR) was confirmed by enzyme-linked immunosorbent
assay (ELISA). Next, we investigated the effect of sAPPalpha on neurite outgrowth
in mouse cortical neurons. Neurite outgrowth was promoted by sAPPalpha, but
sAPPalpha was uneffective in a knockdown of p75(NTR). CONCLUSION: We conclude
that p75(NTR) is the receptor for sAPPalpha to mediate neurotrophic effects.
PMID- 24358170
TI - Evolution of exchangeable copper and relative exchangeable copper through the
course of Wilson's disease in the Long Evans Cinnamon rat.
AB - BACKGROUND: Wilson's disease (WD) is an inherited disorder of copper metabolism
leading to liver failure and/or neurological impairment. Its diagnosis often
remains difficult even with genetic testing. Relative exchangeable copper (REC)
has recently been described as a reliable serum diagnostic marker for WD.
METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to validate the use of
REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study
its relevance under different conditions in comparison with conventional markers.
Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and
biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given
copper-free food. The other groups had normal food. Blood samples were collected
each month and different serum markers for WD (namely ceruloplasmin oxidase
activity, exchangeable copper (CuEXC), total serum copper and REC) and acute
liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat
under normal food developed acute liver failure (ALF), with 40% global mortality.
Serum transaminases and bilirubinemia along with total serum copper and
exchangeable copper levels increased with the onset of acute liver failure. A
correlation was observed between CuEXC values and the severity of ALF. Cut-off
values were different between young and adult rats and evolved because of age
and/or liver failure. Only REC, with values >19%, was able to discriminate LEC
groups from the LE control group at every time point in the study. REC
sensitivity and specificity reached 100% in adults rats.
CONCLUSIONS/SIGNIFICANCE: REC appears to be independent of demographic or
clinical data in LEC rats. It is a very simple and reliable blood test for the
diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be
used as an accurate biomarker of copper overload.
PMID- 24358171
TI - Factors associated with the time to next attack in neuromyelitis optica:
accelerated failure time models with random effects.
AB - BACKGROUND AND OBJECTIVE: Neuromyelitis optica (NMO) is an inflammatory
demyelinating disorder of the central nervous system with a relapsing and
remitting course. We aimed to identify factors associated with the time to next
attack, including the effect of the natural disease course and the diverse
treatment regimens, by applying a longitudinal statistical analysis to the
individual attacks of each patient. METHODS: In total, 184 acute attacks among 58
patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody
were assessed retrospectively. Patient demographics, clinical characteristics at
each attack, and type of treatment during inter-attack periods were assessed. The
dependent variable was defined as the time from each attack to the next attack
(inter-attack interval). An exponential accelerated failure time model with
shared gamma frailty was adapted for statistical analysis. RESULTS: A
multivariable analysis revealed that the time from each attack to the next attack
in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02
1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34
times (95% CI, 1.57-18.13; p = 0.007) with combined azathioprine treatment and
continued oral prednisolone, and by 4.26 times (95% CI, 1.09-16.61; p = 0.037)
with rituximab treatment. CONCLUSION: The time to next attack in NMO can increase
naturally in the later stages of the disease as the number of cumulative attacks
increases. Nevertheless, both combined azathioprine treatment with continued oral
prednisolone and rituximab treatment were also associated with a longer time to
next attack, independently of the natural disease course of NMO.
PMID- 24358173
TI - Detrimental effect of water submersion of stools on development of Strongyloides
stercoralis.
AB - Strongyloidiasis is prevalent in Thailand, yet its prevalence in the south is
lower than in other parts of the country. This might be due to the long rainy
season in the south resulting in stool submersion in water inhibiting worm
development. In this study, the effect of water submersion of fecal samples on
development of Strongyloides stercoralis was investigated. Ten ml of a 1 ? 5
fecal suspension were placed in 15-ml tubes, 35-mm dishes, and 90-mm dishes
producing the depths of 80 mm, 11 mm and 2 mm-suspensions, respectively. The worm
development was followed at 1/6, 4, 6, 8, 10, 12, 14, 16, 24, and 36 h, by
determining the number of filariform larva (FL) generated from agar-plate
cultures (APC). Fecal suspensions kept in tubes and 35-mm dishes showed a decline
in FL yield relative to incubation time and reached zero production 14 h after
incubation. In contrast, the number of FL generated from the suspension kept in
90-mm dishes remained stable up to 36 h. Cumulatively, all tubes and 35-mm dishes
became negative in APC after 14 h while 90-mm dishes remained APC-positive up to
36 h. Adding more water or stool suspension to dishes resulted in a decreased
number of FL. Mechanical aeration of the suspensions in tubes restored an almost
normal FL yield. It appears that the atmospheric air plays a significant role in
growth and development of S. stercoralis in the environment and may be one of
factors which contribute to a lower prevalence of human strongyloidiasis in the
south of Thailand.
PMID- 24358172
TI - Antibodies to heteromeric glycolipid complexes in Guillain-Barre syndrome.
AB - Autoantibodies are infrequently detected in the sera of patients with the
demyelinating form of Guillain-Barre syndrome most commonly encountered in the
Western world, despite abundant circumstantial evidence suggesting their
existence. We hypothesised that antibody specificities reliant on the cis
interactions of neighbouring membrane glycolipids could explain this discrepancy,
and would not have been detected by traditional serological assays using highly
purified preparations of single gangliosides. To assess the frequency of
glycolipid complex antibodies in a Western European cohort of patients GBS we
used a newly developed combinatorial glycoarray methodology to screen against
large range of antigens (11 gangliosides, 8 other single glycolipids and 162
heterodimeric glycolipid complexes). Serum samples of 181 patients from a
geographically defined, Western European cohort of GBS cases were analysed, along
with 161 control sera. Serum IgG binding to single gangliosides was observed in
80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating
electrophysiology. The inclusion of glycolipid complexes increased the positivity
rate in demyelinating disease to 62.4%. There were 40 antigens with statistically
significantly increased binding intensities in GBS as compared to healthy control
sera. Of these, 7 complex antigens and 1 single ganglioside also produced
statistically significantly increased binding intensities in GBS versus
neurological disease controls. The detection of antibodies against specific
complexes was associated with particular clinical features including disease
severity, requirement for mechanical ventilation, and axonal electrophysiology.
This study demonstrates that while antibodies against single gangliosides are
often found in cases with axonal-type electrophysiology, antibodies against
glycolipid complexes predominate in cases with demyelinating electrophysiology,
providing a more robust serum biomarker than has ever been previously available
for such cases. This work confirms the activation of the humoral immune system in
the dysimmune disease process in GBS, and correlates patterns of antigen
recognition with different clinical features.
PMID- 24358174
TI - The V protein of canine distemper virus is required for virus replication in
human epithelial cells.
AB - Canine distemper virus (CDV) becomes able to use human receptors through a single
amino acid substitution in the H protein. In addition, CDV strains possessing an
intact C protein replicate well in human epithelial H358 cells. The present study
showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog
with distemper, failed to replicate in H358 cells, although it possessed an
intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine
substitution at position 267 of the V protein caused this growth defect. Analyses
using H358 cells constitutively expressing the CDV V protein showed that the V
protein with a cysteine, but not that with a tyrosine, at this position
effectively blocked the interferon-stimulated signal transduction pathway, and
supported virus replication of 007Lm in H358 cells. Thus, the V protein as well
as the C protein appears to be functional and essential for CDV replication in
human epithelial cells.
PMID- 24358175
TI - Mating type locus of Chinese black truffles reveals heterothallism and the
presence of cryptic species within the T. indicum species complex.
AB - Tuber spp. are filamentous ascomycetes which establish symbiosis with the roots
of trees and shrub species. By virtue of this symbiosis they produce hypogeous
ascocarps, known as truffles. Filamentous ascomycetes can reproduce by
homothallism or heterothallism depending on the structure and organization of
their mating type locus. The first mating type locus in a truffle species has
been recently characterized in Tuber melanosporum and it has been shown that this
fungus, endemic in Europe, is heterothallic. The availability of sequence
information for T. melanosporum mating type genes is seminal to cloning their
orthologs from other Tuber species and assessing their reproductive mode. Here we
report on the organization of the mating type region in T. indicum, the black
truffle species present in Asia, which is the closest relative to T. melanosporum
and is characterized by an high level of morphological and genetic variability.
The present study shows that T. indicum is also heterothallic. Examination of
Asiatic black truffles belonging to different genetic classes, sorted according
to the sequence polymorphism of the internal transcribed spacer rDNA region, has
revealed sequence variations and rearrangements in both coding and non-coding
regions of the mating type locus, to suggest the existence of cryptic species
within the T. indicum complex. The presence of transposable elements within or
linked to the mating type region suggests a role of these elements in generating
the genotypic diversity present among T. indicum strains. Overall, comparative
analyses of the mating type locus have thus allowed us to tackle taxonomical and
phylogenetic issues within black truffles and make inferences about the evolution
of T. melanosporum-T. indicum lineage. Our results are not only of fundamental
but also of applied relevance as T. indicum produces edible fruit bodies that are
imported also into Europe and thus may represent a biological threat for T.
melanosporum.
PMID- 24358176
TI - Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification
via p38 mitogen-activated protein kinase signaling.
AB - Vascular calcification is associated with significant cardiovascular morbidity
and mortality, and has been demonstrated as an actively regulated process
resembling bone formation. Oxidized low density lipoprotein (Ox-LDL) has been
identified as a regulatory factor involved in calcification of vascular smooth
muscle cells (VSMCs). Additionally, over-expression of recombinant human neutral
sphingomyelinase (N-SMase) has been shown to stimulate VSMC apoptosis, which
plays an important role in the progression of vascular calcification. The aim of
this study is to investigate whether ceramide regulates Ox-LDL-induced
calcification of VSMCs via activation of p38 mitogen-activated protein kinase
(MAPK) pathway. Ox-LDL increased the activity of N-SMase and the level of
ceramide in cultured VSMCs. Calcification and the osteogenic transcription
factor, Msx2 mRNA expression were reduced by N-SMase inhibitor, GW4869 in the
presence of Ox-LDL. Usage of GW4869 inhibited Ox-LDL-induced apoptosis in VSMCs,
an effect which was reversed by C2-ceramide. Additionally, C2-ceramide treatment
accelerated VSMC calcification, with a concomitant increase in ALP activity.
Furthermore, C2-ceramide treatment enhanced Ox-LDL-induced VSMC calcification.
Addition of caspase inhibitor, ZVAD-fmk attenuated Ox-LDL-induced calcification.
Both Ox-LDL and C2-ceramide treatment increased the phosphorylation of p38 MAPK.
Inhibition of p38 MAPK by SB203580 attenuated Ox-LDL-induced calcification of
VSMCs. These data suggest that Ox-LDL activates N-SMase-ceramide signaling
pathway, and stimulates phosphorylation of p38 MAPK, leading to apoptosis in
VSMCs, which initiates VSMC calcification.
PMID- 24358177
TI - Re-visiting insecticide resistance status in Anopheles gambiae from Cote
d'Ivoire: a nation-wide informative survey.
AB - Insecticide resistance constitutes a major threat that may undermine current gain
in malaria control in most endemic countries. National Malaria Control Programmes
(NMCPs) need as much information as possible on the resistance status of malaria
vectors and underlying mechanisms in order to implement the most relevant and
efficient control strategy. Bioassays, biochemical and molecular analysis were
performed on An. gambiae collected in six sentinel sites in Cote d'Ivoire. The
sites were selected on the basis of their bioclimatic status and agricultural
practices. An. gambiae populations across sites showed high levels of resistance
to organochloride, pyrethroid and carbamate insecticides. The kdr and ace-1(R)
mutations were detected in almost all sentinel sites with mosquitoes on the
coastal and cotton growing areas mostly affected by these mutations. At almost
all sites, the levels of detoxifying enzymes (mixed-function oxidases (MFOs), non
specific esterases (NSE) and glutathione-S-transferases (GSTs)) in An. gambiae
populations were significantly higher than the levels found in the susceptible
strain Kisumu. Pre-exposure of mosquitoes to PBO, an inhibitor of MFOs and NSEs,
significantly increased mortality rates to pyrethroids and carbamates in
mosquitoes but resistance in most cases was not fully synergised by PBO,
inferring a residual role of additional mechanisms, including kdr and ace-1 site
insensitivity. The large distribution of resistance in Cote d'Ivoire raises an
important question of whether to continue to deploy pyrethroid-based long-lasting
insecticidal nets (LLINs) and insecticide residual spraying (IRS) towards which
resistance continues to rise with no guarantee that the level of resistance would
not compromise their efficacy. Innovative strategies that combine insecticide and
synergists in LLINs or spatially LLIN and an effective non-pyrethroid insecticide
for IRS could be in the short term the best practice for the NMCP to manage
insecticide resistance in malaria vectors in Cote d'Ivoire and other endemic
countries facing resistance.
PMID- 24358178
TI - Food selectivity and diet switch can explain the slow feeding of herbivorous
coral-reef fishes during the morning.
AB - Most herbivorous coral-reef fishes feed slower in the morning than in the
afternoon. Given the typical scarcity of algae in coral reefs, this behavior
seems maladaptive. Here we suggest that the fishes' slow feeding during the
morning is an outcome of highly selective feeding on scarcely found green algae.
The rarity of the food requires longer search time and extended swimming tracks,
resulting in lower bite rates. According to our findings by noon the fish seem to
stop their search and switch to indiscriminative consumption of benthic algae,
resulting in apparent higher feeding rates. The abundance of the rare preferable
algae gradually declines from morning to noon and seems to reach its lowest
levels around the switch time. Using in situ experiments we found that the
feeding pattern is flexible, with the fish exhibiting fast feeding rates when
presented with ample supply of preferable algae, regardless of the time of day.
Analyses of the fish's esophagus content corroborated our conclusion that their
feeding was highly selective in the morning and non-selective in the afternoon.
Modeling of the fishes' behavior predicted that the fish should perform a diel
diet shift when the preferred food is relatively rare, a situation common in most
coral reefs found in a warm, oligotrophic ocean.
PMID- 24358179
TI - The effect of antigen retrieval on cells fixed in 10% neutral buffered formalin
followed by transfer to 70% ethanol.
AB - Fixation in 10% neutral buffered formalin prior to transfer to 70% ethanol for
one week has been shown to adequately preserve immunorecognition of PCNA,
cytokeratins AE1/AE3 and EGFr. This study investigated whether 12 hrs fixation in
10% NBF plus transfer to 70% ethanol for 4 weeks would similarly preserve
immunorecognition to an extent where antigen retrieval (AR) used to reverse the
masking effects of fixation on some antigens would not be necessary. Two cell
lines, DU145 and SKOV3 were grown on coverslips and fixed either for 684 hrs in
10% NBF or for 12 hrs in 10% NBF which was then replaced with 70% ethanol for 672
hrs. The second experiment had the same design except an additional set of cells
were subjected to heat-induced AR concomitantly. PCNA, cytokeratins AE1/AE3, and
EGFr (membrane and cytoplasmic) were used to evaluate the effects of
immunorecognition. Fixation in 10% NBF for 12 hrs plus transfer to 70% ethanol
for 672 hrs did not preserve immunorecognition of PCNA adequately in either cell
lines. Cytokeratins immunoreactivity was preserved by transfer to 70% ethanol.
Cytoplasmic EGFr antigens were not adversely affected by 10% NBF fixation in
either cell line and transfer to 70% ethanol had limited effects. With AR, there
was little recovery of PCNA immunorecognition on cells fixed in only 10% NBF, but
almost complete recovery for cells transferred to 70% ethanol. For cytokeratins
there was complete recovery of immunorecognition either with only 10% NBF or 12
hrs plus transfer to 70% ethanol. For EGFr, AR resulted in complete loss of
immunorecognition following either treatment. This study indicated that 12 hrs of
fixation in 10% NBF plus transfer to 70% ethanol for 4 weeks with AR resulted in
recovery of immunorecognition for PCNA and cytokeratins, but standard methods of
AR caused loss of immunorecognition of EGFr.
PMID- 24358180
TI - Perceived sexual orientation based on vocal and facial stimuli is linked to self
rated sexual orientation in Czech men.
AB - Previous research has shown that lay people can accurately assess male sexual
orientation based on limited information, such as face, voice, or behavioral
display. Gender-atypical traits are thought to serve as cues to sexual
orientation. We investigated the presumed mechanisms of sexual orientation
attribution using a standardized set of facial and vocal stimuli of Czech men.
Both types of stimuli were rated for sexual orientation and masculinity
femininity by non-student heterosexual women and homosexual men. Our data showed
that by evaluating vocal stimuli both women and homosexual men can judge sexual
orientation of the target men in agreement with their self-reported sexual
orientation. Nevertheless, only homosexual men accurately attributed sexual
orientation of the two groups from facial images. Interestingly, facial images of
homosexual targets were rated as more masculine than heterosexual targets. This
indicates that attributions of sexual orientation are affected by stereotyped
association between femininity and male homosexuality; however, reliance on such
cues can lead to frequent misjudgments as was the case with the female raters.
Although our study is based on a community sample recruited in a non-English
speaking country, the results are generally consistent with the previous research
and thus corroborate the validity of sexual orientation attributions.
PMID- 24358181
TI - Hyperoxia exposure impairs nephrogenesis in the neonatal rat: role of HIF-1alpha.
AB - Preterm neonates are exposed at birth to high oxygen concentrations relative to
the intrauterine environment. We have previously shown in a rat model that a
hyperoxic insult results in a reduced nephron number in adulthood. Therefore, the
aim of this study was to determine the effects of transient neonatal hyperoxia
exposure on nephrogenesis. Sprague-Dawley rat pups were raised in 80% O2 or room
air from P3 to P10. Pups (n = 12/group, 6 males and 6 females) were sacrificed at
P5 (during active nephrogenesis) and at P10 (after the completion of
nephrogenesis). Hyperoxia exposure resulted in a significant reduction in both
nephrogenic zone width and glomerular diameter at P5, and a significantly
increased apoptotic cell count; however, nephron number at P10 was not affected.
HIF-1alpha expression in the developing kidney was significantly reduced
following hyperoxia exposure. Systemic administration of the HIF-1alpha
stabilizer dimethyloxalylglycine (DMOG) resulted in enhanced expression of HIF
1alpha and improved nephrogenesis: kidneys from hyperoxia-exposed pups treated
with DMOG exhibited a nephrogenic zone width and glomerular diameter similar to
room-air controls. These findings demonstrate that neonatal hyperoxia exposure
results in impaired nephrogenesis, which may be at least in part HIF-1alpha
mediated. Although nephron number was not significantly reduced at the completion
of nephrogenesis, early indicators of maldevelopment suggest the potential for
accelerated nephron loss in adulthood. Overall, this study supports the premise
that prematurely born neonates exposed to high oxygen levels after birth are
vulnerable to impaired renal development.
PMID- 24358182
TI - Structural analysis of influenza A virus matrix protein M1 and its self
assemblies at low pH.
AB - Influenza A virus matrix protein M1 is one of the most important and abundant
proteins in the virus particles broadly involved in essential processes of the
viral life cycle. The absence of high-resolution data on the full-length M1 makes
the structural investigation of the intact protein particularly important. We
employed synchrotron small-angle X-ray scattering (SAXS), analytical
ultracentrifugation and atomic force microscopy (AFM) to study the structure of
M1 at acidic pH. The low-resolution structural models built from the SAXS data
reveal a structurally anisotropic M1 molecule consisting of a compact NM-fragment
and an extended and partially flexible C-terminal domain. The M1 monomers co
exist in solution with a small fraction of large clusters that have a layered
architecture similar to that observed in the authentic influenza virions. AFM
analysis on a lipid-like negatively charged surface reveals that M1 forms ordered
stripes correlating well with the clusters observed by SAXS. The free NM-domain
is monomeric in acidic solution with the overall structure similar to that
observed in previously determined crystal structures. The NM-domain does not
spontaneously self assemble supporting the key role of the C-terminus of M1 in
the formation of supramolecular structures. Our results suggest that the
flexibility of the C-terminus is an essential feature, which may be responsible
for the multi-functionality of the entire protein. In particular, this
flexibility could allow M1 to structurally organise the viral membrane to
maintain the integrity and the shape of the intact influenza virus.
PMID- 24358183
TI - Microbiota and metabolite profiling reveal specific alterations in bacterial
community structure and environment in the cystic fibrosis airway during
exacerbation.
AB - Chronic polymicrobial infections of the lung are the foremost cause of morbidity
and mortality in cystic fibrosis (CF) patients. The composition of the microbial
flora of the airway alters considerably during infection, particularly during
patient exacerbation. An understanding of which organisms are growing, their
environment and their behaviour in the airway is of importance for designing
antibiotic treatment regimes and for patient prognosis. To this end, we have
analysed sputum samples taken from separate cohorts of CF and non-CF subjects for
metabolites and in parallel, and we have examined both isolated DNA and RNA for
the presence of 16S rRNA genes and transcripts by high-throughput sequencing of
amplicon or cDNA libraries. This analysis revealed that although the population
size of all dominant orders of bacteria as measured by DNA- and RNA- based
methods are similar, greater discrepancies are seen with less prevalent
organisms, some of which we associated with CF for the first time. Additionally,
we identified a strong relationship between the abundance of specific anaerobes
and fluctuations in several metabolites including lactate and putrescine during
patient exacerbation. This study has hence identified organisms whose occurrence
within the CF microbiome has been hitherto unreported and has revealed potential
metabolic biomarkers for exacerbation.
PMID- 24358184
TI - Finding markers that make a difference: DNA pooling and SNP-arrays identify
population informative markers for genetic stock identification.
AB - Genetic stock identification (GSI) using molecular markers is an important tool
for management of migratory species. Here, we tested a cost-effective alternative
to individual genotyping, known as allelotyping, for identification of highly
informative SNPs for accurate genetic stock identification. We estimated allele
frequencies of 2880 SNPs from DNA pools of 23 Atlantic salmon populations using
Illumina SNP-chip. We evaluated the performance of four common strategies (global
F ST, pairwise F ST, Delta and outlier approach) for selection of the most
informative set of SNPs and tested their effectiveness for GSI compared to random
sets of SNP and microsatellite markers. For the majority of cases, SNPs selected
using the outlier approach performed best followed by pairwise F ST and Delta
methods. Overall, the selection procedure reduced the number of SNPs required for
accurate GSI by up to 53% compared with randomly chosen SNPs. However, GSI
accuracy was more affected by populations in the ascertainment group rather than
the ranking method itself. We demonstrated for the first time the compatibility
of different large-scale SNP datasets by compiling the largest population genetic
dataset for Atlantic salmon to date. Finally, we showed an excellent performance
of our top SNPs on an independent set of populations covering the main European
distribution range of Atlantic salmon. Taken together, we demonstrate how
combination of DNA pooling and SNP arrays can be applied for conservation and
management of salmonids as well as other species.
PMID- 24358185
TI - High prevalence of malaria parasitemia and anemia among hospitalized children in
Rakai, Uganda.
AB - BACKGROUND: There is a paucity of data on malaria among hospitalized children in
malaria endemic areas. We determined the prevalence, presentation and treatment
outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda.
METHODS: Children under five years hospitalized in Kalisizo hospital or Bikira
health center in Rakai district, Uganda between May 2011 and May 2012 were
enrolled and followed-up until discharge, death or referral. Data were collected
on social-demographic characteristics, current and past illnesses and clinical
signs and symptoms. Blood smears, hemoglobin (Hgb) levels and HIV testing were
performed from finger/heel prick blood. The associations between malaria
infection and other factors were estimated using log-binomial regression to
estimate adjusted prevalence risk ratios (aPRR) and 95% confidence intervals
(CIs), controlling for clustering at health facilities. RESULTS: 2471 children
were enrolled. The most common medical presentations were fever (96.2%), cough
(61.7%), vomiting (44.2%), diarrhea (20.8%), and seizures (16.0%). The prevalence
of malaria parasitemia was 54.6%. Children with malaria were more likely to
present with a history of fever (aPRR 2.23; CI 1.18-4.24) and seizures (aPRR
1.12; CI 1.09-1.16). Confirmed malaria was significantly lower among girls than
boys (aPRR 0.92; CI 0.91-0.93), HIV infected children (aPRR 0.60 CI 0.52-0.71),
and children with diarrhea (aPRR 0.76; CI 0.65-0.90). The overall prevalence of
anemia (Hgb<10 g/dl) was 56.3% and severe anemia (Hgb<6 g/dL) was 17.8%. Among
children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received
blood transfusion. Malaria associated mortality was 0.6%. CONCLUSION: There was a
high prevalence of malaria parasitemia and anemia among inpatient children under
five years. Malaria prevention is a priority in this population.
PMID- 24358186
TI - Serum levels of acylcarnitines are altered in prediabetic conditions.
AB - OBJECTIVE: The role of mitochondrial function in the complex pathogenesis of type
2 diabetes is not yet completely understood. Therefore, the aim of this study was
to investigate serum concentrations of short-, medium- and long-chain
acylcarnitines as markers of mitochondrial function in volunteers with normal,
impaired or diabetic glucose control. METHODS: Based on a 75 g oral glucose
tolerance test, 1019 studied subjects were divided into a group with normal
glucose tolerance (NGT; n = 636), isolated impaired fasting glycaemia (IFG; n =
184), impaired glucose tolerance (IGT; n = 87) or type 2 diabetes (T2D; n = 112).
Serum concentrations of free carnitine and 24 acylcarnitines were measured by
mass spectrometry. RESULTS: Serum levels of acetylcarnitine (C2),
propionylcarnitine (C3), octanoylcarnitine (C8),
malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH), hexanoylcarnitine (C6),
octenoylcarnitine (C8:1), decanoylcarnitine (C10), decenoylcarnitine (C10:1),
dodecanoylcarnitine (C12), tetradecenoylcarnitine (C14:1),
tetradecadienylcarnitine (C14:2), hydroxytetradecanoylcarnitine (C14OH),
hydroxyhexadecanoylcarnitine (C16OH) and octadecenoylcarnitine (C18:1) were
significantly different among the groups (all p<0.05 adjusted for age, gender and
BMI). Between the prediabetic states C14:1, C14:2 and C18:1 showed significantly
higher serum concentrations in persons with IGT (p<0.05). Compared to T2D the IFG
and the IGT subjects showed lower serum concentrations of
malonylcarnitine/hydroxybutyrylcarnitine (C3DC+C4OH) (p<0.05). CONCLUSION:
Alterations in serum concentrations of several acylcarnitines, in particular
tetradecenoylcarnitine (C14:1), tetradecadienylcarnitine (C14:2),
octadecenoylcarnitine (C18:1) and malonylcarnitine/hydroxybutyrylcarnitine
(C3DC+C4OH) are associated not only with T2D but also with prediabetic states.
PMID- 24358187
TI - MicroRNA profiling of primary cutaneous large B-cell lymphomas.
AB - Aberrant expression of microRNAs is widely accepted to be pathogenetically
involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs
profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet
described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell
lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma
(PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal
center B-cell (GCB)-genotype, respectively. We performed high-throughput
sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT
to establish microRNA profiles. Cluster analysis of the complete microRNome could
not distinguish between the two subtypes, but 16 single microRNAs were found to
be differentially expressed. Single microRNA RT-qPCR was conducted on formalin
fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher
expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as
compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in
ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed
between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their
microRNA profiles. In contrast to their gene expression profile, they only show
slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal
DLBCL.
PMID- 24358188
TI - Enhancement of anti-inflammatory activity of Aloe vera adventitious root extracts
through the alteration of primary and secondary metabolites via salicylic acid
elicitation.
AB - Aloe vera (Asphodeloideae) is a medicinal plant in which useful secondary
metabolites are plentiful. Among the representative secondary metabolites of Aloe
vera are the anthraquinones including aloe emodin and chrysophanol, which are
tricyclic aromatic quinones synthesized via a plant-specific type III polyketide
biosynthesis pathway. However, it is not yet clear which cellular responses can
induce the pathway, leading to production of tricyclic aromatic quinones. In this
study, we examined the effect of endogenous elicitors on the type III polyketide
biosynthesis pathway and identified the metabolic changes induced in elicitor
treated Aloe vera adventitious roots. Salicylic acid, methyl jasmonate, and
ethephon were used to treat Aloe vera adventitious roots cultured on MS liquid
media with 0.3 mg/L IBA for 35 days. Aloe emodin and chrysophanol were remarkably
increased by the SA treatment, more than 10-11 and 5-13 fold as compared with
untreated control, respectively. Ultra-performance liquid chromatography
electrospray ionization mass spectrometry analysis identified a total of 37 SA
induced compounds, including aloe emodin and chrysophanol, and 3 of the compounds
were tentatively identified as tricyclic aromatic quinones. Transcript
accumulation analysis of polyketide synthase genes and gas chromatography mass
spectrometry showed that these secondary metabolic changes resulted from
increased expression of octaketide synthase genes and decreases in malonyl-CoA,
which is the precursor for the tricyclic aromatic quinone biosynthesis pathway.
In addition, anti-inflammatory activity was enhanced in extracts of SA-treated
adventitious roots. Our results suggest that SA has an important role in
activation of the plant specific-type III polyketide biosynthetic pathway, and
therefore that the efficacy of Aloe vera as medicinal agent can be improved
through SA treatment.
PMID- 24358189
TI - Structure-based analysis of A19D, a variant of transthyretin involved in familial
amyloid cardiomyopathy.
AB - Transthyretin (TTR) is a tetrameric beta-sheet-rich protein. Its deposits have
been implicated in four different amyloid diseases. Although aggregation of the
wild-type sequence is responsible for the senile form of the disease, more than
one hundred variants have been described thus far, most of which confer a more
amyloidogenic character to TTR, mainly because they compromise the stability of
the protein in relation to monomer formation, which upon misfolding is
intrinsically aggregation-prone. We report the case of a Brazilian patient
suffering from a severe cardiomyopathy who carries a rare mutation in exon 2 of
the TTR gene that results in an Ala to Asp substitution at position 19 (A19D).
The putative pathogenic mechanisms of this variant were analyzed in silico. We
constructed a structural model for the A19D tetramer from which its thermodynamic
stability was compared to that displayed by the V30M (more amyloidogenic than WT
TTR) and T119M (non-amyloidogenic) variants. The FoldX force field predicted that
A19D and V30M are 10.88 and 8.07 kCal/mol less stable than the WT-TTR, while
T119M is 5.15 kCal/mol more stable, which is consistent with the aggregation
propensities exhibited by these variants. We analyzed the step in which the
tetramer-dimer-monomer-unfolded monomer equilibrium might contribute the most to
the increased or decreased amyloidogenicity in each variant. Our results suggest
that the concentration of four non-native negative charges occur inside thyroxine
binding channels, and the loss of contacts at both the tetrameric and dimeric
interfaces would account for an overall decreased stability of the tetramer and
the consequent enhanced amyloidogenicity of the A19D variant. As far as we know,
this is the first description of a non-V30M mutation in Brazil.
PMID- 24358190
TI - Phylodynamics of the emergence of influenza viruses after cross-species
transmission.
AB - Human populations are constantly exposed to emerging pathogens such as influenza
A viruses that result from cross-species transmissions. Generally these sporadic
events are evolutionary dead-ends, but occasionally, viruses establish themselves
in a new host that offers a novel genomic context to which the virus must adjust
to avoid attenuation. However, the dynamics of this process are unknown. Here we
present a novel method to characterize the time it takes to G+C composition at
third codon positions (GC3 content) of influenza viruses to adjust to that of a
new host. We compare the inferred dynamics in two subtypes, H1N1 and H3N2, based
on complete genomes of viruses circulating in humans, swine and birds between
1900-2009. Our results suggest that both subtypes have the same fast-adjusting
genes, which are not necessarily those with the highest absolute rates of
evolution, but those with the most relaxed selective pressures. Our analyses
reveal that NA and NS2 genes adjust the fastest to a new host and that selective
pressures of H3N2 viruses are relaxed faster than for H1N1. The asymmetric nature
of these processes suggests that viruses with the greatest adjustment potential
to humans are coming from both birds and swine for H3N2, but only from birds for
H1N1.
PMID- 24358191
TI - Expression profile of CYP1A1 and CYP1B1 enzymes in colon and bladder tumors.
AB - BACKGROUND: The cytochrome P450 CYP1A1 and CYP1B1 enzymes are involved in
carcinogenesis via activation of pro-carcinogenic compounds to carcinogenic
metabolites. CYP1A1 and CYP1B1 have shown elevated levels in human tumors as
determined by qRT-PCR and immunohistochemical studies. However studies that have
examined CYP1 expression by enzyme activity assays are limited. RESULTS: In the
current study the expression of CYP1A1 and CYP1B1 was investigated in a panel of
human tumors of bladder and colorectal origin by qRT-PCR and enzyme activity
assays. The results demonstrated that 35% (7/20) of bladder tumors and 35% (7/20)
of colon tumors overexpressed active CYP1 enzymes. CYP1B1 mRNA was overexpressed
in 65% and 60% of bladder and colon tumors respectively, whereas CYP1A1 was
overexpressed in 65% and 80% of bladder and colon tumors. Mean mRNA levels of
CYP1B1 and CYP1A1 along with mean CYP1 activity were higher in bladder and colon
tumors compared to normal tissues (p<0.05). Statistical analysis revealed CYP1
expression levels to be independent of TNM status. Moreover, incubation of tumor
microsomal protein in 4 bladder and 3 colon samples with a CYP1B1 specific
antibody revealed a large reduction (72.5 +/- 5.5 % for bladder and 71.8 +/- 7.2%
for colon) in catalytic activity, indicating that the activity was mainly
attributed to CYP1B1 expression. CONCLUSIONS: The study reveals active CYP1
overexpression in human tumors and uncovers the potential use of CYP1 enzymes and
mainly CYP1B1 as targets for cancer therapy.
PMID- 24358192
TI - A systematic review of mapping strategies for the sonification of physical
quantities.
AB - The field of sonification has progressed greatly over the past twenty years and
currently constitutes an established area of research. This article aims at
exploiting and organizing the knowledge accumulated in previous experimental
studies to build a foundation for future sonification works. A systematic review
of these studies may reveal trends in sonification design, and therefore support
the development of design guidelines. To this end, we have reviewed and analyzed
179 scientific publications related to sonification of physical quantities. Using
a bottom-up approach, we set up a list of conceptual dimensions belonging to both
physical and auditory domains. Mappings used in the reviewed works were
identified, forming a database of 495 entries. Frequency of use was analyzed
among these conceptual dimensions as well as higher-level categories. Results
confirm two hypotheses formulated in a preliminary study: pitch is by far the
most used auditory dimension in sonification applications, and spatial auditory
dimensions are almost exclusively used to sonify kinematic quantities. To detect
successful as well as unsuccessful sonification strategies, assessment of mapping
efficiency conducted in the reviewed works was considered. Results show that a
proper evaluation of sonification mappings is performed only in a marginal
proportion of publications. Additional aspects of the publication database were
investigated: historical distribution of sonification works is presented,
projects are classified according to their primary function, and the sonic
material used in the auditory display is discussed. Finally, a mapping-based
approach for characterizing sonification is proposed.
PMID- 24358194
TI - Gene flow and maintenance of genetic diversity in invasive mosquitofish (Gambusia
holbrooki).
AB - Genetic analyses contribute to studies of biological invasions by mapping the
origin and dispersal patterns of invasive species occupying new territories.
Using microsatellite loci, we assessed the genetic diversity and spatial
population structure of mosquitofish (Gambusia holbrooki) that had invaded
Spanish watersheds, along with the American locations close to the suspected
potential source populations. Mosquitofish populations from the Spanish streams
that were studied had similar levels of genetic diversity to the American
samples; therefore, these populations did not appear to have undergone
substantial losses of genetic diversity during the invasion process. Population
structure analyses indicated that the Spanish populations fell into four main
clusters, which were primarily associated with hydrography. Dispersal patterns
indicated that local populations were highly connected upstream and downstream
through active dispersal, with an average of 21.5% fish from other locations in
each population. After initially introducing fish to one location in a given
basin, such dispersal potential might contribute to the spread and colonization
of suitable habitats throughout the entire river basin. The two-dimension
isolation-by-distance pattern here obtained, indicated that the human-mediated
translocation of mosquitofish among the three study basins is a regular
occurrence. Overall, both phenomena, high natural dispersal and human
translocation, favor gene flow among river basins and the retention of high
genetic diversity, which might help retain the invasive potential of mosquitofish
populations.
PMID- 24358193
TI - Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy.
AB - Tubulo-interstitial damage is a common finding in the chronically diseased kidney
and is characterized by ongoing inflammation and fibrosis leading to renal
dysfunction and end-stage renal disease. Upon kidney injury, endogenous ligands
can be released which are recognized by innate immune sensors to alarm innate
immune system. A new family of innate sensors is the family of TREM (triggering
receptor expressed on myeloid cell). TREM1 is an activating receptor and requires
association with transmembrane adapter molecule DAP12 (DNAX-associated protein
12) for cell signaling. TREM1-DAP12 pathway has a cross-talk with intracellular
signaling pathways of several Toll-like receptors (TLRs) and is able to amplify
TLR signaling and thereby contributes to the magnitude of inflammation. So far,
several studies have shown that TLRs play a role in obstructive nephropathy but
the contribution of TREM1-DAP12 herein is unknown. Therefore, we studied TREM1
expression in human and murine progressive renal diseases and further
investigated the role for TREM1-DAP12 by subjecting wild-type (WT), TREM1/3
double KO and DAP12 KO mice to murine unilateral ureter obstruction (UUO) model.
In patients with hydronephrosis, TREM1 positive cells were observed in renal
tissue. We showed that in kidneys from WT mice, DAP12 mRNA and TREM1 mRNA and
protein levels were elevated upon UUO. Compared to WT mice, DAP12 KO mice
displayed less renal MCP-1, KC and TGF-beta1 levels and less influx of
macrophages during progression of UUO, whereas TREM1/3 double KO mice displayed
less renal MCP-1 level. Renal fibrosis was comparable in WT, TREM1/3 double KO
and DAP12 KO mice. We conclude that DAP12, partly through TREM1/3, is involved in
renal inflammation during progression of UUO.
PMID- 24358195
TI - Stress conditions triggering mucoid morphotype variation in Burkholderia species
and effect on virulence in Galleria mellonella and biofilm formation in vitro.
AB - Burkholderia cepacia complex (Bcc) bacteria are opportunistic pathogens causing
chronic respiratory infections particularly among cystic fibrosis patients.
During these chronic infections, mucoid-to-nonmucoid morphotype variation occurs,
with the two morphotypes exhibiting different phenotypic properties. Here we show
that in vitro, the mucoid clinical isolate Burkholderia multivorans D2095 gives
rise to stable nonmucoid variants in response to prolonged stationary phase,
presence of antibiotics, and osmotic and oxidative stresses. Furthermore, in
vitro colony morphotype variation within other members of the Burkholderia genus
occurred in Bcc and non-Bcc strains, irrespectively of their clinical or
environmental origin. Survival to starvation and iron limitation was comparable
for the mucoid parental isolate and the respective nonmucoid variant, while
susceptibility to antibiotics and to oxidative stress was increased in the
nonmucoid variants. Acute infection of Galleria mellonella larvae showed that, in
general, the nonmucoid variants were less virulent than the respective parental
mucoid isolate, suggesting a role for the exopolysaccharide in virulence. In
addition, most of the tested nonmucoid variants produced more biofilm biomass
than their respective mucoid parental isolate. As biofilms are often associated
with increased persistence of pathogens in the CF lungs and are an indicative of
different cell-to-cell interactions, it is possible that the nonmucoid variants
are better adapted to persist in this host environment.
PMID- 24358196
TI - Mdm20 stimulates polyQ aggregation via inhibiting autophagy through Akt-Ser473
phosphorylation.
AB - Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the
catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes
N-acetylation during de novo protein synthesis initiation; however, recent
evidence from yeast suggests that NatB also affects post-translational
modification of tropomyosin, which is involved in intracellular sorting of
aggregated proteins. We hypothesized that an acetylation complex such as NatB may
contribute to protein clearance and/or proteostasis in mammalian cells. Using a
poly glutamine (polyQ) aggregation system, we examined whether the NatB complex
or its components affect protein aggregation in rat primary cultured hippocampal
neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over
expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown
(KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly
reduced. Although Mdm20 directly associates with Nat5, the overall cellular
localization of the two proteins was slightly distinct, and Mdm20 apparently co
localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate
appearance of LC3 was evident, suggesting the induction of autophagy. Consistent
with this notion, phosphorylation of Akt, most notably at Ser473, was greatly
reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called
auxiliary subunit of the translation-coupled protein N-acetylation complex,
contributes to protein clearance and/or aggregate formation by affecting the
phosphorylation level of Akt indepenently from the function of Nat5.
PMID- 24358197
TI - A study of the immunoloregulation of double filtration plasmapheresis in
maintenance hemodialysis patients with chronic hepatitis C.
AB - Although a large number of drugs have been used to treat chronic hepatitis C
(CHC), there still remains a great challenge to treat maintenance hemodialysis
(MHD) patients with chronic hepatitis C. To clarify the immunnoloregulation of
double filtration plasmapheresis (DFPP) in MHD patients with CHC, DFPP was
performed in 20 MHD patients with CHC (HCV-antibody positive, serum HCV RNA >500
IU/ml more than 6 months and HCV genotype 1b). The clinical data was collected
and peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry at
the time of hour 0, hour 3, day 3, day 7 and day 28 after the DFPP, respectively.
Serum HCV particles could be removed partially by the DFPP. The titer of serum
HCV RNA could remain in a lower level even 28 days after the treatment. Compared
to MHD patients without HCV infection, the frequencies of innate immune cells
were similar in MHD patients with CHC, while Th1/Th2 was elevated and the
frequencies of regulatory T (Treg) cells were higher in those MHD patients with
CHC. The frequencies of monocytes and natural killer (NK) cells remained after
the DFPP in MHD patients with CHC. There were no significant changes of Th1, Th2
and Th1/Th2 in PBMC after DFPP. DFPP could reduce the frequencies of Th17 cells
and Treg cells in PBMC from 7 days after DFPP in MHD patients with CHC. DFPP
could partially remove the serum HCV particles mechanically. The titer of HCV RNA
could remain in a lower level at least for 28 days probably due to the
redistribution of the immunocytes in circulation.
PMID- 24358198
TI - Apnea-induced cortical BOLD-fMRI and peripheral sympathoneural firing response
patterns of awake healthy humans.
AB - End-expiratory breath-holds (BH) and Mueller manoeuvres (MM) elicit large
increases in muscle sympathetic nerve activity (MSNA). In 16 healthy humans (9?,
35 +/- 4 years) we used functional magnetic resonance imaging with blood oxygen
level-dependent (BOLD) contrast to determine the cortical network associated with
such sympathoexcitation. We hypothesized that increases in MSNA evoked by these
simulated apneas are accompanied by BOLD contrast changes in the insular cortex,
thalamus and limbic cortex. A series of 150 whole-brain images were collected
during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg). The
identical protocol was repeated separately with MSNA recorded from the fibular
nerve. The time course of the sympathoexcitatory response to both breathing tasks
were correlated with whole-brain BOLD signal changes. Brain sites demonstrating
both positive (activation) and negative (deactivation) correlations with the MSNA
time course were identified. Sympathetic burst incidence increased (p<0.001) from
29 +/- 6 (rest) to 49 +/- 6 (BH) and 47 +/- 6 bursts/100 heartbeats (MM).
Increased neural activity (Z-scores) was identified in the right posterior and
anterior insular cortices (3.74, 3.64), dorsal anterior cingulate (3.42),
fastigial and dentate cerebellar nuclei (3.02, 3.34). Signal intensity decreased
in the left posterior insula (3.28) and ventral anterior cingulate (3.01). Apnea
both activates and inhibits elements of a cortical network involved in the
generation of sympathetic outflow. These findings identify a neuroanatomical
substrate to guide future investigations into central mechanisms contributing to
disorders characterized by elevated basal MSNA and exaggerated sympathetic
responses to simulated apneas such as sleep apnea and heart failure.
PMID- 24358199
TI - Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient
mice.
AB - Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2
disease. We previously reported that Bscl2 (-/-) mice develop lipodystrophy of
white adipose tissue (WAT) due to unbridled lipolysis. The residual epididymal
WAT (EWAT) displays a browning phenotype with much smaller lipid droplets (LD)
and higher expression of brown adipose tissue marker proteins. Here we used
targeted lipidomics and gene expression profiling to analyze lipid profiles as
well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/-)
mice. Analysis of total saponified fatty acids revealed that the residual EWAT of
Bscl2(-/-) mice contained a much higher proportion of oleic 18:1n9 acid
concomitant with a lower proportion of palmitic 16:0 acid, as well as increased
n3- polyunsaturated fatty acids (PUFA) remodeling. The acyl chains in major
species of triacylglyceride (TG) and diacylglyceride (DG) in the residual EWAT of
Bscl2(-/-) mice were also enriched with dietary fatty acids. These changes could
be reflected by upregulation of several fatty acid elongases and desaturases.
Meanwhile, Bscl2(-/-) adipocytes from EWAT had increased gene expression in lipid
uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and
peroxisomal beta-oxidation genes were also markedly increased in Bscl2(-/-)
adipocytes, highlighting that these machineries were accelerated to shunt the
lipolysis liberated fatty acids through uncoupling to dissipate energy. The
residual subcutaneous white adipose tissue (ScWAT) was not browning but displays
similar changes in lipid metabolism. Overall, our data emphasize that, other than
being essential for adipocyte differentiation, Bscl2 is also important in fatty
acid remodeling and energy homeostasis.
PMID- 24358200
TI - Isolation and characterization of highly replicable hepatitis C virus genotype 1a
strain HCV-RMT.
AB - Multiple genotype 1a clones have been reported, including the very first
hepatitis C virus (HCV) clone called H77. The replication ability of some of
these clones has been confirmed in vitro and in vivo, although this ability is
somehow compromised. We now report a newly isolated genotype 1a clone, designated
HCV-RMT, which has the ability to replicate efficiently in patients, chimeric
mice with humanized liver, and cultured cells. An authentic subgenomic replicon
cell line was established from the HCV-RMT sequence with spontaneous introduction
of three adaptive mutations, which were later confirmed to be responsible for
efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral
genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive
mutations was maintained for more than 2 months in HuH-7 cells. One clone
selected from the transfected cells had a high copy number, and its supernatant
could infect naive HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into
the liver of chimeric mice with humanized liver resulted in vigorous replication,
similar to inoculation with the parental patient's serum. A study of virus
replication using HCV-RMT derivatives with various combinations of adaptive
mutations revealed a clear inversely proportional relationship between in vitro
and in vivo replication abilities. Thus, we suggest that HCV-RMT and its
derivatives are important tools for HCV genotype 1a research and for determining
the mechanism of HCV replication in vitro and in vivo.
PMID- 24358201
TI - Defectors cannot be detected during"small talk" with strangers.
AB - To account for the widespread human tendency to cooperate in one-shot social
dilemmas, some theorists have proposed that cooperators can be reliably detected
based on ethological displays that are difficult to fake. Experimental findings
have supported the view that cooperators can be distinguished from defectors
based on "thin slices" of behavior, but the relevant cues have remained elusive,
and the role of the judge's perspective remains unclear. In this study, we
followed triadic conversations among unacquainted same-sex college students with
unannounced dyadic one-shot prisoner's dilemmas, and asked participants to guess
the PD decisions made toward them and among the other two participants. Two other
sets of participants guessed the PD decisions after viewing videotape of the
conversations, either with foreknowledge (informed), or without foreknowledge
(naive), of the post-conversation PD. Only naive video viewers approached better
than-chance prediction accuracy, and they were significantly accurate at
predicting the PD decisions of only opposite-sexed conversation participants.
Four ethological displays recently proposed to cue defection in one-shot social
dilemmas (arms crossed, lean back, hand touch, and face touch) failed to predict
either actual defection or guesses of defection by any category of observer. Our
results cast doubt on the role of "greenbeard" signals in the evolution of human
prosociality, although they suggest that eavesdropping may be more informative
about others' cooperative propensities than direct interaction.
PMID- 24358202
TI - Replicated evidence of absence of association between serum S100B and (risk of)
psychotic disorder.
AB - BACKGROUND: S100B is a potential marker of neurological and psychiatric illness.
In schizophrenia, increased S100B levels, as well as associations with acute
positive and persisting negative symptoms, have been reported. It remains unclear
whether S100B elevation, which possibly reflects glial dysfunction, is the
consequence of disease or compensatory processes, or whether it is an indicator
of familial risk. METHODS: Serum samples were acquired from two large independent
family samples (n = 348 and n = 254) in the Netherlands comprising patients with
psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with
psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B
was analyzed with a Liaison automated chemiluminescence system. Associations
between familial risk of psychotic disorder and S100B were examined. RESULTS:
Results showed that S100B levels in patients (P) and siblings (S) were not
significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI
0.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI -0.009 to 0.008, p = 0.926;
and dataset 2: P vs. C: B = 0.008, 95% CI -0.011 to 0.028, p = 0.410; S vs. C: B
= 0.002, 95% CI -0.016 to 0.021, p = 0.797). In patients, negative symptoms were
positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in
one of the datasets, however with failure of replication in the other. There was
no significant association between S100B and positive symptoms or present use or
type of antipsychotic medication. CONCLUSIONS: S100B is neither an intermediate
phenotype, nor a trait marker for psychotic illness.
PMID- 24358203
TI - Plasmodium vivax population structure and transmission dynamics in Sabah
Malaysia.
AB - Despite significant progress in the control of malaria in Malaysia, the complex
transmission dynamics of P. vivax continue to challenge national efforts to
achieve elimination. To assess the impact of ongoing interventions on P. vivax
transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a
total of 97 isolates (8 recurrences) from across Sabah, with a focus on two
districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year
period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub
populations. Significant differentiation (F ST = 0.243) was observed between KM
and KK, located just 130 Km apart. Consistent with low endemic transmission,
infection complexity was modest in both KM (mean MOI = 1.38) and KK (mean MOI =
1.19). However, population diversity remained moderate (H E = 0.583 in KM and H
E = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic
transmission dynamics. The haplotypes of these isolates declined in frequency
over time, but persisted at low frequency throughout the study duration. A
diverse array of low frequency isolates were detected in both KM and KK, some
likely reflecting remnants of previous expansions. In accordance with clonal
expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK
and KM) declined sharply when identical haplotypes were represented once (I A (S)
= 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8
recurrences, likely to be relapses, were homologous to the prior infection. These
recurrences may promote the persistence of parasite lineages, sustaining local
diversity. In summary, Sabah's shrinking P. vivax population appears to have
rendered this low endemic setting vulnerable to epidemic expansions. Migration
may play an important role in the introduction of new parasite strains leading to
epidemic expansions, with important implications for malaria elimination.
PMID- 24358204
TI - Polymorphisms of CYP51A1 from cholesterol synthesis: associations with birth
weight and maternal lipid levels and impact on CYP51 protein structure.
AB - We investigated the housekeeping cytochrome P450 CYP51A1 encoding lanosterol
14alpha-demethylase from cholesterol synthesis that was so far not directly
linked to human disorders. By direct sequencing of CYP51A1 in 188 women with
spontaneous preterm delivery and 188 unrelated preterm infants (gestational age
<37 weeks) we identified 22 variants where 10 are novel and rare. In infants
there were two novel CYP51A1 variants where damaging effects of p.Tyr145Asp from
the substrate recognition region, but not p.Asn193Asp, were predicted by
PolyPhen2 and SIFT. This was confirmed by molecular modeling showing that
Tyr145Asp substitution results in changed electrostatic potential of the CYP51
protein surface and lengthened distance to the heme which prevents hydrogen
bonding. The CYP51 Tyr145Asp mutation is rare and thus very interesting for
further structure/function relationship studies. From the 12 identified known
variants rs6465348 was chosen for family based association studies due to its
high minor allele frequency. Interestingly, this CYP51A1 common variant
associates with small for gestational age weight in newborns (p = 0.028) and
lower blood total cholesterol and low density lipoprotein cholesterol levels in
mothers in 2nd trimester of pregnancy (p = 0.042 and p = 0.046 respectively). Our
results indicate a new link between a cholesterol synthesis gene CYP51A1 and
pregnancy pathologies.
PMID- 24358205
TI - MIR376A is a regulator of starvation-induced autophagy.
AB - BACKGROUND: Autophagy is a vesicular trafficking process responsible for the
degradation of long-lived, misfolded or abnormal proteins, as well as damaged or
surplus organelles. Abnormalities of the autophagic activity may result in the
accumulation of protein aggregates, organelle dysfunction, and autophagy
disorders were associated with various diseases. Hence, mechanisms of autophagy
regulation are under exploration. METHODS: Over-expression of hsa-miR-376a1
(shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy
related targets of the miRNA were predicted using Microcosm Targets and MIRanda
bioinformatics tools and experimentally validated. Endogenous miRNA was blocked
using antagomirs and the effects on target expression and autophagy were
analyzed. Luciferase tests were performed to confirm that 3' UTR sequences in
target genes were functional. Differential expression of MIR376A and the related
MIR376B was compared using TaqMan quantitative PCR. RESULTS: Here, we
demonstrated that, a microRNA (miRNA) from the DLK1/GTL2 gene cluster, MIR376A,
played an important role in autophagy regulation. We showed that, amino acid and
serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7
and Huh7 cells. MIR376A shared the same seed sequence and had overlapping targets
with MIR376B, and similarly blocked the expression of key autophagy proteins
ATG4C and BECN1 (Beclin 1). Indeed, 3' UTR sequences in the mRNA of these
autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir
tests showed that, endogenous MIR376A was participating to the control of ATG4C
and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A
accelerated starvation-induced autophagic activity. Interestingly, MIR376A and
MIR376B levels were increased with different kinetics in response to starvation
stress and tissue-specific level differences were also observed, pointing out to
an overlapping but miRNA-specific biological role. CONCLUSIONS: Our findings
underline the importance of miRNAs encoded by the DLK1/GTL2 gene cluster in
stress-response control mechanisms, and introduce MIR376A as a new regulator of
autophagy.
PMID- 24358206
TI - PaCS is a novel cytoplasmic structure containing functional proteasome and
inducible by cytokines/trophic factors.
AB - A variety of ubiquitinated protein-containing cytoplasmic structures has been
reported, from aggresomes to aggresome-like induced structures/sequestosomes or
particle-rich cytoplasmic structures (PaCSs) that we recently observed in some
human diseases. Nevertheless, the morphological and cytochemical patterns of the
different structures remain largely unknown thus jeopardizing their univocal
identification. Here, we show that PaCSs resulted from proteasome and
polyubiquitinated protein accumulation into well-demarcated, membrane-free,
cytoskeleton-poor areas enriched in glycogen and glycosaminoglycans. A major
requirement for PaCS detection by either electron or confocal microscopy was the
addition of osmium to aldehyde fixatives. However, by analyzing living cells, we
found that proteasome chymotrypsin-like activity concentrated in well-defined
cytoplasmic structures identified as PaCSs by ultrastructural morphology and
immunocytochemistry of the same cells. PaCSs differed ultrastructurally and
cytochemically from sequestosomes which may coexist with PaCSs. In human
dendritic or natural killer cells, PaCSs were induced in vitro by
cytokines/trophic factors during differentiation/activation from blood
progenitors. Our results provide evidence that PaCS is indeed a novel distinctive
cytoplasmic structure which may play a critical role in the ubiquitin-proteasome
system response to immune, infectious or proneoplastic stimuli.
PMID- 24358207
TI - Nicotine-induced expression of low-density lipoprotein receptor in oral
epithelial cells.
AB - BACKGROUND: Nicotine use is one of the most important risk factors for the
development of cardiovascular and periodontal diseases. Numerous reports have
suggested the possible contribution of disturbed lipid metabolism for the
development of both disease groups. Despite these observations, little is known
about the relationship between tobacco smoking and the development of these
diseases. Our previous microarray data revealed that nicotine induced low-density
lipoprotein receptor (LDLR) expression in oral epithelial cells (OECs). The aim
of the present study was to confirm nicotine-mediated LDLR induction and to
elucidate the signaling mechanisms leading to the augmented expression of LDLR in
OECs. METHODS AND RESULTS: LDLR and nicotinic acetylcholine receptor (nAChR)
subunit expression was detected by real-time PCR. The production of LDLR was
demonstrated by immunofluorescence staining. nAChR-mediated LDLR induction was
examined by pre-incubation of the cells with its specific inhibitor, alpha
bungarotoxin (alpha-BTX). The functional importance of transcription factor
specific protein 1 (Sp1) was examined by luciferase assay, mithramycin pre
incubation or by small interfering RNA (siRNA) transfection. The specific binding
of Sp1 to R3 region of LDLR 5'-untranslated region was demonstrated with
electrophoretic mobility shift assay (EMSA) and streptavidin-agarose
precipitation assay followed by western blotting. The results confirmed that
nicotine induced LDLR expression at the transcriptional level. Nicotine was
sensed by nAChR and the signal was transduced by Sp1 which bound to the R3 region
of LDLR gene. Augmented production of LDLR in the gingival epithelial cells was
further demonstrated by immunofluorescence staining using the gingival tissues
obtained from the smoking patients. CONCLUSIONS: Taken together, the results
suggested that nicotine might contribute to the development of both
cardiovascular and periodontal diseases by inducing the LDLR in OECs thereby
disturbing lipid metabolism.
PMID- 24358208
TI - Integration of miRNA and protein profiling reveals coordinated neuroadaptations
in the alcohol-dependent mouse brain.
AB - The molecular mechanisms underlying alcohol dependence involve different
neurochemical systems and are brain region-dependent. Chronic Intermittent
Ethanol (CIE) procedure, combined with a Two-Bottle Choice voluntary drinking
paradigm, represents one of the best available animal models for alcohol
dependence and relapse drinking. MicroRNAs, master regulators of the cellular
transcriptome and proteome, can regulate their targets in a cooperative,
combinatorial fashion, ensuring fine tuning and control over a large number of
cellular functions. We analyzed cortex and midbrain microRNA expression levels
using an integrative approach to combine and relate data to previous protein
profiling from the same CIE-subjected samples, and examined the significance of
the data in terms of relative contribution to alcohol consumption and dependence.
MicroRNA levels were significantly altered in CIE-exposed dependent mice compared
with their non-dependent controls. More importantly, our integrative analysis
identified modules of coexpressed microRNAs that were highly correlated with CIE
effects and predicted target genes encoding differentially expressed proteins.
Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with
specific microRNA modules. Our results provide evidence that microRNA
orchestrated translational imbalances are driving the behavioral transition from
alcohol consumption to dependence. This study represents the first attempt to
combine ex vivo microRNA and protein expression on a global scale from the same
mammalian brain samples. The integrative systems approach used here will improve
our understanding of brain adaptive changes in response to drug abuse and
suggests the potential therapeutic use of microRNAs as tools to prevent or
compensate multiple neuroadaptations underlying addictive behavior.
PMID- 24358209
TI - Resilience and controllability of dynamic collective behaviors.
AB - The network paradigm is used to gain insight into the structural root causes of
the resilience of consensus in dynamic collective behaviors, and to analyze the
controllability of the swarm dynamics. Here we devise the dynamic signaling
network which is the information transfer channel underpinning the swarm dynamics
of the directed interagent connectivity based on a topological neighborhood of
interactions. The study of the connectedness of the swarm signaling network
reveals the profound relationship between group size and number of interacting
neighbors, which is found to be in good agreement with field observations on
flock of starlings [Ballerini et al. (2008) Proc. Natl. Acad. Sci. USA, 105:
1232]. Using a dynamical model, we generate dynamic collective behaviors enabling
us to uncover that the swarm signaling network is a homogeneous clustered small
world network, thus facilitating emergent outcomes if connectedness is
maintained. Resilience of the emergent consensus is tested by introducing
exogenous environmental noise, which ultimately stresses how deeply intertwined
are the swarm dynamics in the physical and network spaces. The availability of
the signaling network allows us to analytically establish for the first time the
number of driver agents necessary to fully control the swarm dynamics.
PMID- 24358210
TI - Moesin controls clathrin-mediated S1PR1 internalization in T cells.
AB - The lipid mediator sphingosine 1-phosphate (S1P) regulates a wide range of
cellular activities, including vascular maturation, angiogenesis, and immune-cell
trafficking. Among the five known receptors for S1P (S1PR1-S1PR5), S1PR1 is a
critical regulator of lymphocyte trafficking: its signaling is required for
lymphocyte egress from lymphoid organs, while its down-modulation by agonist
induced internalization is a prerequisite for lymphocyte entry into lymphoid
organs from the bloodstream. Despite the importance of S1PR1 down-regulation in
determining lymphocyte behavior, the molecular mechanism of its internalization
in lymphocytes has not been defined. Here we show that agonist-induced S1PR1
internalization in T cells occurs via clathrin-mediated endocytosis and is
regulated by moesin, an ezrin-radixin-moesin (ERM) family member. In S1P
stimulated T cells, S1PR1 relocalized within clathrin-coated vesicles (CCVs) and
early endosomes, and S1PR1 internalization was blocked when clathrin was
pharmacologically inhibited. Stimulating moesin-deficient T cells with S1P failed
to induce S1PR1 internalization and CCV formation. Furthermore, treating moesin
deficient mice with FTY720, an S1P receptor agonist known to internalize S1PR1,
caused delayed lymphopenia, and lymphocytes isolated from FTY720-treated moesin
deficient mice still responded to S1P ex vivo in chemotaxis assays. These results
reveal a novel role for moesin in regulating clathrin-dependent S1PR1
internalization through CCV formation.
PMID- 24358211
TI - Hepatitis C virus genotype diversity among intravenous drug users in Yunnan
Province, Southwestern China.
AB - BACKGROUND: Recently, high proportions (15.6%-98.7%) of intravenous drug users
(IDUs) in China were found to be positive for hepatitis C virus (HCV). Yunnan
Province is located in southwestern China and borders one of the world's most
important opium-producing regions, thus it is an important drug trafficking route
to other regions of China. METHODOLOGY/PRINCIPAL FINDINGS: Here, we assessed 100
HCV-positive plasma samples from IDUs who were enrolled through the Kunming
Center for Disease Control and Prevention in 2012. HCV C/E1 fragments were PCR
amplified and sequenced. We identified eight HCV subtypes (1a, 1b, 3a, 3b, 6a,
6n, 6u and 6v), of which genotype 6 was most predominant (frequency, 47%)
followed by genotypes 3 (41%) and 1 (12%). HCV subtypes 6n (30%) and 3b (29%)
were most common and were identified in 59% of the IDUs. We compared HCV
genotypes among IDUs in Yunnan Province with those from other regions and found
that the distribution patterns of HCV genotypes in Yunnan Province were similar
to those in southern China, but different from those in eastern China. However,
the distribution patterns of HCV subtypes varied among Yunnan Province and
southern China, despite the shared similar genotypes. A comparison of the current
data with those previously reported showed that the frequency of HCV genotype 6
increased from 25% to 47% within 5 years, especially subtypes 6a (5% to 15%) and
6n (11.2% to 30%). In contrast, the frequencies of subtypes 3b and 1b decreased
by almost 50% within 5 years. CONCLUSION/SIGNIFICANCE: Our results provided
further information to support the assertion that drug trafficking routes
influence HCV transmission patterns among IDUs in Yunnan Province. The frequency
of HCV genotypes and subtypes changed rapidly among IDUs in Yunnan Province and
subtypes 6a and 6n may have originated in Vietnam and Myanmar, respectively.
PMID- 24358212
TI - Correlation of epididymal protease inhibitor and fibronectin in human semen.
AB - OBJECTIVE: Epididymal protease inhibitor (Eppin) was located on the surface of
spermatozoa and modulates the liquefaction of human semen. Here, we identify the
correlative protein partner of Eppin to explore the molecular mechanism of
liquefaction of human semen. METHODS: (1) Human seminal vesicle proteins were
transferred on the membrane by Western blotting and separated by 2-D
electrophoresis and incubated in recombinant Eppin. The correlative protein was
identified by Mass Spectrometry (MS) (2). Western blotting was used to determine
the relation of rEppin and rFibronectin(Fn); (3) Co-localization in spermatozoa
were detected using immunofluorescence; (4) Correalation of Eppin and Fn was
proved by co-immunoprecipitation. RESULTS: Fn was identified as the binding
partner of recombinant Eppin by MS. Recombinant of Eppin was made and
demonstrated that the Eppin fragment binds the fn 607-1265 fragment. The Eppin-Fn
complex presents on the sperm tail and particularly in the midpiece region of
human ejaculated spermatozoa. Immunoprecipitation indicated that Eppin in the
spermatozoa lysates was complexed with Fn. CONCLUSIONS: Our study demonstrates
that Eppin and Fn bind to each other in human semen and on human ejaculated
spermatozoa. Eppin-Fn complex may involve in semen coagulation, liquefaction and
the survival and preparation of spermatozoa for fertility in the female
reproductive tract.
PMID- 24358213
TI - Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction
protein downregulation can be ameliorated by citicoline.
AB - This study explores the effect of citicoline on the permeability and expression
of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia
conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to
induce endothelial barrier breakdown model on human umbilical vein endothelial
cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The
effect of citicoline on endothelial barrier breakdown models was determined at
either low or high concentrations. FITC-Dextran flux was used to examine the
endothelial permeability. The expression of TJPs was measured by
immunofluorescence, Real-time PCR and Western Blot methods. Results showed that
hypoxia or OGD increased the permeability of HUVECs accompanied with down
regulation of occludens-1 (ZO-1) and occludin at both mRNA and protein levels.
Similarly in bEnd.3s, hypoxia increased the permeability and decreased the
expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased
the permeability in these two models, which paralleled with elevated expression
of TJPs. The data demonstrate that citicoline restores the barrier function of
endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the
expression of TJPs.
PMID- 24358214
TI - Food-pharma convergence in medical nutrition- best of both worlds?
AB - At present, industries within the health and life science sector are moving
towards one another resulting in new industries such as the medical nutrition
industry. Medical nutrition products are specific nutritional compositions for
intervention in disease progression and symptom alleviation. Industry
convergence, described as the blurring of boundaries between industries, plays a
crucial role in the shaping of new markets and industries. Assuming that the
medical nutrition industry has emerged from the convergence between the food and
pharma industries, it is crucial to research how and which distinct industry
domains have contributed to establish this relatively new industry. The first two
stages of industry convergence (knowledge diffusion and consolidation) are
measured by means of patent analysis. First, the extent of knowledge diffusion
within the medical nutrition industry is graphed in a patent citation
interrelations network. Subsequently the consolidation based on technological
convergence is determined by means of patent co-classification. Furthermore, the
medical nutrition core domain and technology interrelations are measured by means
of a cross impact analysis. This study proves that the medical nutrition industry
is a result of food and pharma convergence. It is therefore crucial for medical
nutrition companies to effectively monitor technological developments within as
well as across industry boundaries. This study further reveals that although the
medical nutrition industry's core technology domain is food, technological
development is mainly driven by pharmaceutical/pharmacological technologies
Additionally, the results indicate that the industry has surpassed the knowledge
diffusion stage of convergence, and is currently in the consolidation phase of
industry convergence. Nevertheless, while the medical nutrition can be classified
as an industry in an advanced phase of convergence, one cannot predict that the
pharma and food industry segments will completely converge or whether the medical
industry will become an individual successful industry.
PMID- 24358215
TI - Neurobiological signatures of alcohol dependence revealed by protein profiling.
AB - Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to
tolerance, dependence, and behavioral modifications. Previous proteomic studies
in human alcoholics and animal models have identified candidate alcoholism
related proteins. However, recent evidences suggest that alcohol dependence is
caused by changes in co-regulation that are invisible to single protein-based
analysis. Here, we analyze global proteomics data to integrate differential
expression, co-expression networks, and gene annotations to unveil key
neurobiological rearrangements associated with the transition to alcohol
dependence modeled by a Chronic Intermittent Ethanol (CIE), two-bottle choice
(2BC) paradigm. We analyzed cerebral cortices (CTX) and midbrains (MB) from male
C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and
represents one of the best available animal models for alcohol dependence and
relapse drinking. CIE induced significant changes in protein levels in dependent
mice compared with their non-dependent controls. Multiple protein isoforms showed
region-specific differential regulation as a result of post-translational
modifications. Our integrative analysis identified modules of co-expressed
proteins that were highly correlated with CIE treatment. We found that modules
most related to the effects of CIE treatment coordinate molecular imbalances in
endocytic- and energy-related pathways, with specific proteins involved, such as
dynamin-1. The qRT-PCR experiments validated both differential and co-expression
analyses, and the correspondence among our data and previous genomic and
proteomic studies in humans and rodents substantiates our findings. The changes
identified above may play a key role in the escalation of ethanol consumption
associated with dependence. Our approach to alcohol addiction will advance
knowledge of brain remodeling mechanisms and adaptive changes in response to drug
abuse, contribute to understanding of organizational principles of CTX and MB
proteomes, and define potential new molecular targets for treating alcohol
addiction. The integrative analysis employed here highlight the advantages of
systems approaches in studying the neurobiology of alcohol addiction.
PMID- 24358216
TI - Unique T cells with unconventional cytokine profiles induced in the livers of
mice during Schistosoma mansoni infection.
AB - During infection with Schistosoma, serious hepatic disorders are induced in the
host. The liver possesses unique immune systems composed of specialized cells
that differ from those of other immune competent organs or tissues. Host immune
responses change dramatically during Schistosoma mansoni infection; in the early
phase, Th1-related responses are induced, whereas during the late phase Th2
reactions dominate. Here, we describe unique T cell populations induced in the
liver of mice during the period between Th1- and Th2-phases, which we term the
transition phase. During this phase, varieties of immune cells including T
lymphocytes increase in the liver. Subsets of CD4(+) T cells exhibit unique
cytokine production profiles, simultaneously producing both IFN-gamma and IL-13
or both IFN-gamma and IL-4. Furthermore, cells triply positive for IFN-gamma, IL
13 and IL-4 also expand in the S. mansoni-infected liver. The induction of these
unique cell populations does not occur in the spleen, indicating it is a
phenomenon specific to the liver. In single hepatic CD4(+) T cells showing the
unique cytokine profiles, both T-bet and GATA-3 are expressed. Thus, our studies
show that S. mansoni infection triggers the induction of hepatic T cell subsets
with unique cytokine profiles.
PMID- 24358217
TI - Alternative splicing events is not a key event for gene expression regulation in
uremia.
AB - BACKGROUND: The control of gene expression in the course of chronic kidney
disease (CKD) is not well addressed. Alternative splicing is a common way to
increase complexity of proteins. More than 90% of human transcripts are
alternatively spliced. We hypothesised that CKD can induce modification of the
alternative splicing machinery. METHODS: During mutation screening in autosomal
dominant polycystic kidney disease, we identified in mononuclear cells (PBMC), an
alternative splicing event on the exon 30 of PKD1 gene, the gene implicated in
this disease. This alternative splice variant was not correlated with the cystic
disease but with CKD. To confirm the association between this variant and CKD, a
monocentric clinical study was performed with 3 different groups according to
their kidney function (CKD5D, CKD3-5 and normal kidney function). An exon
microarray approach was used to highlight splicing events in whole human genome
in a normal cell model (fibroblasts) incubated with uremic serum. Alternative
splicing variants identified were confirmed by RT-PCR. RESULTS: The splicing
variant of the exon 30 of PKD1 was more frequent in PBMCs from patients with CKD
compared to control. With the microarray approach, despite the analysis of more
than 230 000 probes, we identified 36 genes with an abnormal splicing index
evocating splicing event in fibroblasts exposed to uremic serum. Only one
abnormal splicing event in one gene, ADH1B, was confirmed by RT-PCR. CONCLUSION:
We observed two alternative spliced genes in two different cell types associated
with CKD. Alternative splicing could play a role in the control of gene
expression during CKD but it does not seem to be a major mechanism.
PMID- 24358218
TI - A versatile technique for the in vivo imaging of human tumor xenografts using
near-infrared fluorochrome-conjugated macromolecule probes.
AB - Here, we present a versatile method for detecting human tumor xenografts in vivo,
based on the enhanced permeability and retention (EPR) effect, using near
infrared (NIR) fluorochrome-conjugated macromolecule probes. Bovine serum albumin
(BSA) and two immunoglobulins-an anti-human leukocyte antigen (HLA) monoclonal
antibody and isotype control IgG2a-were labeled with XenoLight CF770 fluorochrome
and used as NIR-conjugated macromolecule probes to study whole-body imaging in a
variety of xenotransplantation mouse models. NIR fluorescent signals were
observed in subcutaneously transplanted BxPC-3 (human pancreatic cancer) cells
and HCT 116 (colorectal cancer) cells within 24 h of NIR-macromolecule probe
injection, but the signal from the fluorochrome itself or from the NIR-conjugated
small molecule (glycine) injection was not observed. The accuracy of tumor
targeting was confirmed by the localization of the NIR-conjugated immunoglobulin
within the T-HCT 116 xenograft (in which the orange-red fluorescent protein
tdTomato was stably expressed by HCT 116 cells) in the subcutaneous
transplantation model. However, there was no significant difference in the NIR
signal intensity of the region of interest between the anti-HLA antibody group
and the isotype control group in the subcutaneous transplantation model.
Therefore, the antibody accumulation within the tumor in vivo is based on the EPR
effect. The liver metastasis generated by an intrasplenic injection of T-HCT 116
cells was clearly visualized by the NIR-conjugated anti-HLA probe but not by the
orange-red fluorescent signal derived from the tdTomato reporter. This result
demonstrated the superiority of the NIR probes over the tdTomato reporter protein
at enhancing tissue penetration. In another xenograft model, patient-derived
xenografts (PDX) of LC11-JCK (human non-small cell lung cancer) were successfully
visualized using the NIR-conjugated macromolecule probe without any genetic
modification. These results suggested that NIR-conjugated macromolecule,
preferably, anti-HLA antibody probe is a valuable tool for the detection of human
tumors in experimental metastasis models using whole-body imaging.
PMID- 24358219
TI - Microstructural, densitometric and metabolic variations in bones from rats with
normal or altered skeletal states.
AB - BACKGROUND: High resolution MUCT, and combined MUPET/CT have emerged as non
invasive techniques to enhance or even replace dual energy X-ray absorptiometry
(DXA) as the current preferred approach for fragility fracture risk assessment.
The aim of this study was to assess the ability of uPET/CT imaging to
differentiate changes in rat bone tissue density and microstructure induced by
metabolic bone diseases more accurately than current available methods. METHODS:
Thirty three rats were divided into three groups of control, ovariectomy and
vitamin-D deficiency. At the conclusion of the study, animals were subjected to
glucose ((18)FDG) and sodium fluoride (Na(18)F) PET/CT scanning. Then, specimens
were subjected to uCT imaging and tensile mechanical testing. RESULTS: Compared
to control, those allocated to ovariectomy and vitamin D deficiency groups showed
4% and 22% (significant) increase in (18)FDG uptake values, respectively. DXA
based bone mineral density was higher in the vitamin D deficiency group when
compared to the other groups (cortical bone), yet MUCT-based apparent and mineral
density results were not different between groups. DXA-based bone mineral density
was lower in the ovariectomy group when compared to the other groups (cancellous
bone); yet MUCT-based mineral density results were not different between groups,
and the MUCT-based apparent density results were lower in the ovariectomy group
compared to the other groups. CONCLUSION: PET and micro-CT provide an accurate
three-dimensional measurement of the changes in bone tissue mineral density, as
well as microstructure for cortical and cancellous bone and metabolic activity.
As osteomalacia is characterized by impaired bone mineralization, the use of
densitometric analyses may lead to misinterpretation of the condition as
osteoporosis. In contrast, uCT alone and in combination with the PET component
certainly provides an accurate three-dimensional measurement of the changes in
both bone tissue mineral density, as well as microstructure for cortical and
cancellous bone and metabolic activity.
PMID- 24358221
TI - Upregulation of cleavage and polyadenylation specific factor 4 in lung
adenocarcinoma and its critical role for cancer cell survival and proliferation.
AB - Cleavage and polyadenylation specific factor 4 (CPSF4), a member of CPSF complex,
plays a key role in mRNA polyadenylation and mRNA 3' ends maturation. However,
its possible role in lung cancer pathogenesis is unknown. In this study, we
investigated the biological role and clinical significance of CPSF4 in lung
cancer growth and survival and elucidated its underlying molecular mechanisms. We
found that CPSF4 was highly expressed in lung adenocarcinoma cell lines and tumor
tissue but was undetectable in 8 normal human tissues. We also found that CPSF4
overexpression was correlated with poor overall survival in patients with lung
adenocarcinomas (P<0.001). Multivariate survival analyses revealed that higher
CPSF4 expression was an independent prognostic factor for overall survival of the
patients with lung adenocarcinomas. Suppression of CPSF4 by siRNA inhibited lung
cancer cells proliferation, colony formation, and induced apoptosis. Mechanism
studies revealed that these effects were achieved through simultaneous modulation
of multiple signaling pathways. Knockdown of CPSF4 expression by siRNA markedly
inhibited the phosphorylation of PI3K, AKT and ERK1/2 and JNK proteins. In
contrast, the ectopic expression of CPSF4 had the opposite effects. Moreover,
CPSF4 knockdown also induced the cleavage of caspase-3 and caspse-9 proteins.
Collectively, these results demonstrate that CPSF4 plays a critical role in
regulating lung cancer cell proliferation and survival and may be a potential
prognostic biomarker and therapeutic target for lung adenocarcinoma.
PMID- 24358220
TI - Disrupted topological organization in whole-brain functional networks of heroin
dependent individuals: a resting-state FMRI study.
AB - Neuroimaging studies have shown that heroin addiction is related to abnormalities
in widespread local regions and in the functional connectivity of the brain.
However, little is known about whether heroin addiction changes the topological
organization of whole-brain functional networks. Seventeen heroin-dependent
individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were
enrolled, and the resting-state functional magnetic resonance images (RS-fMRI)
were acquired from these subjects. We constructed the brain functional networks
of HDIs and NCs, and compared the between-group differences in network
topological properties using graph theory method. We found that the HDIs showed
decreases in the normalized clustering coefficient and in small-worldness
compared to the NCs. Furthermore, the HDIs exhibited significantly decreased
nodal centralities primarily in regions of cognitive control network, including
the bilateral middle cingulate gyrus, left middle frontal gyrus, and right
precuneus, but significantly increased nodal centralities primarily in the left
hippocampus. The between-group differences in nodal centralities were not
corrected by multiple comparisons suggesting these should be considered as an
exploratory analysis. Moreover, nodal centralities in the left hippocampus were
positively correlated with the duration of heroin addiction. Overall, our results
indicated that disruptions occur in the whole-brain functional networks of HDIs,
findings which may be helpful in further understanding the mechanisms underlying
heroin addiction.
PMID- 24358222
TI - Glycated haemoglobin is inversely related to serum vitamin D levels in type 2
diabetic patients.
AB - OBJECTIVE: A correlation between glucose control and 25(OH)D metabolism has been
suggested by previous studies. However, this correlation has not yet been
evaluated considering the impact of chronic complications of type 2 diabetes,
especially the presence of nephropathy. Thus, the aim of this study was to
determine the correlation between A1C and 25(OH)D in a well characterized cohort
of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We cross-sectionally
examined the association between A1C and serum 25(OH) D in 715 type 2 diabetic
patients attending our clinic during the years 2011-2012. The average age was
68+/-12 years (range 26-94 years). The relation between A1C and serum 25(OH)D
levels was modelled by multiple linear regression analyses. RESULTS: Serum
25(OH)D levels were inversely associated with A1C levels (r = -0.116, p = .003).
This relation maintains its independence in the multivariate analysis after
adjusting for age, sex, A1C, BMI, treatment and duration of diabetes and
nephropathy. CONCLUSIONS: In type 2 diabetic patients, high A1C levels are
associated with low concentrations of serum 25(OH)D independently of duration of
diabetes, diabetic treatment and nephropathy. Future studies are needed to
clarify the biological relation between glucose control and vitamin D metabolism
in type 2 diabetes.
PMID- 24358223
TI - Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide
switch to improve the efficacy and safety of T cell adoptive immunotherapy for
lymphoma.
AB - Modification of T cells with chimeric antigen receptors (CAR) has emerged as a
promising treatment modality for human malignancies. Integration of co
stimulatory domains into CARs can augment the activation and function of
genetically targeted T cells against tumors. However, the potential for
insertional mutagenesis and toxicities due to the infused cells have made
development of safe methods for removing transferred cells an important
consideration. We have genetically modified human T cells with a lentiviral
vector to express a CD20-CAR containing both CD28 and CD137 co-stimulatory
domains, a "suicide gene" relying on inducible activation of caspase 9 (iC9), and
a truncated CD19 selectable marker. Rapid expansion (2000 fold) of the transduced
T cells was achieved in 28 days after stimulation with artificial antigen
presenting cells. Transduced T cells exhibited effective CD20-specific cytotoxic
activity in vitro and in a mouse xenograft tumor model. Activation of the iC9
suicide switch resulted in efficient removal of transduced T cells both in vitro
and in vivo. Our work demonstrates the feasibility and promise of this approach
for treating CD20(+) malignancies in a safe and more efficient manner. A phase I
clinical trial using this approach in patients with relapsed indolent B-NHL is
planned.
PMID- 24358224
TI - Global assessment of Antrodia cinnamomea-induced microRNA alterations in
hepatocarcinoma cells.
AB - Recent studies have demonstrated a potent anticancer potential of medicinal
fungus Antrodia cinnamomea, especially against hepatocarcinoma. These studies,
however, were performed with prolonged treatments, and the early anticancer
events remain missing. To probe the early anticancer mechanisms of A. cinnamomea,
we treated SK-Hep-1 liver cancer cell with A. cinnamomea fruiting body extract
for 2 and 4 hours, sequenced RNA samples with next-generation sequencing
approach, and profiled the genome-wide miRNA and mRNA transcriptomes. Results
unmistakably associated the early anticancer effect of A. cinnamomea fruiting
body extract with a global downregulation of miRNAs which occurred solely in the
A. cinnamomea fruiting body extract-treated SK-Hep-1 cells. Moreover, the
inhibitory effect of A. cinnamomea fruiting body extract upon cancer miRNAs
imposed no discrimination against any particular miRNA species, with oncomirs miR
21, miR-191 and major oncogenic clusters miR-17-92 and miR-106b-25 among the most
severely downregulated. Western blotting further indicated a decrease in Drosha
and Dicer proteins which play a key role in miRNA biogenesis, together with an
increase of XRN2 known to participate in miRNA degradation pathway. Transcriptome
profiling followed by GO and pathway analyses indicated that A. cinnamomea
induced apoptosis, which was tightly associated with a downregulation of PI3K/AKT
and MAPK pathways. Phosphorylation assay further suggested that JNK and c-Jun
were closely involved in the apoptotic process. Taken together, our data
indicated that the anticancer effect of A. cinnamomea can take place within a few
hours by targeting multiple proteins and the miRNA system. A. cinnamomea
indiscriminately induced a global downregulation of miRNAs by simultaneously
inhibiting the key enzymes involved in miRNA maturation and activating XRN2
protein involved in miRNA degradation. Collapsing of the miRNA system together
with downregulation of cell growth and survival pathways and activation of JNK
signaling unleash the extrinsic and intrinsic apoptosis pathways, leading to the
cancer cell death.
PMID- 24358225
TI - Complete mitochondrial genomes of chimpanzee- and gibbon-derived Ascaris isolated
from a zoological garden in southwest China.
AB - Roundworms (Ascaridida: Nematoda), one of the most common soil-transmitted
helminths (STHs), can cause ascariasis in various hosts worldwide, ranging from
wild to domestic animals and humans. Despite the veterinary and health importance
of the Ascaridida species, little or no attention has been paid to roundworms
infecting wild animals including non-human primates due to the current taxon
sampling and survey bias in this order. Importantly, there has been considerable
controversy over the years as to whether Ascaris species infecting non-human
primates are the same as or distinct from Ascaris lumbricoides infecting humans.
Herein, we first characterized the complete mitochondrial genomes of two
representative Ascaris isolates derived from two non-human primates, namely,
chimpanzees (Pan troglodytes) and gibbons (Hylobates hoolock), in a zoological
garden of southwest China and compared them with those of A. lumbricoides and the
congeneric Ascaris suum as well as other related species in the same order, and
then used comparative mitogenomics, genome-wide nucleotide sequence identity
analysis, and phylogeny to determine whether the parasites from chimpanzees and
gibbons represent a single species and share genetic similarity with A.
lumbricoides. Taken together, our results yielded strong statistical support for
the hypothesis that the chimpanzee- and gibbon-derived Ascaris represent a single
species that is genetically similar to A. lumbricoides, consistent with the
results of previous morphological and molecular studies. Our finding should
enhance public alertness to roundworms originating from chimpanzees and gibbons
and the mtDNA data presented here also serves to enrich the resource of markers
that can be used in molecular diagnostic, systematic, population genetic, and
evolutionary biological studies of parasitic nematodes from either wild or
domestic hosts.
PMID- 24358226
TI - Neural correlates of the in-group memory advantage on the encoding and
recognition of faces.
AB - People have a memory advantage for faces that belong to the same group, for
example, that attend the same university or have the same personality type. Faces
from such in-group members are assumed to receive more attention during memory
encoding and are therefore recognized more accurately. Here we use event-related
potentials related to memory encoding and retrieval to investigate the neural
correlates of the in-group memory advantage. Using the minimal group procedure,
subjects were classified based on a bogus personality test as belonging to one of
two personality types. While the electroencephalogram was recorded, subjects
studied and recognized faces supposedly belonging to the subject's own and the
other personality type. Subjects recognized in-group faces more accurately than
out-group faces but the effect size was small. Using the individual behavioral in
group memory advantage in multivariate analyses of covariance, we determined
neural correlates of the in-group advantage. During memory encoding (300 to 1000
ms after stimulus onset), subjects with a high in-group memory advantage elicited
more positive amplitudes for subsequently remembered in-group than out-group
faces, showing that in-group faces received more attention and elicited more
neural activity during initial encoding. Early during memory retrieval (300 to
500 ms), frontal brain areas were more activated for remembered in-group faces
indicating an early detection of group membership. Surprisingly, the parietal
old/new effect (600 to 900 ms) thought to indicate recollection processes
differed between in-group and out-group faces independent from the behavioral in
group memory advantage. This finding suggests that group membership affects
memory retrieval independent of memory performance. Comparisons with a previous
study on the other-race effect, another memory phenomenon influenced by social
classification of faces, suggested that the in-group memory advantage is
dominated by top-down processing whereas the other-race effect is also influenced
by extensive perceptual experience.
PMID- 24358227
TI - Morphological characterization of Mycobacterium tuberculosis in a MODS culture
for an automatic diagnostics through pattern recognition.
AB - Tuberculosis control efforts are hampered by a mismatch in diagnostic technology:
modern optimal diagnostic tests are least available in poor areas where they are
needed most. Lack of adequate early diagnostics and MDR detection is a critical
problem in control efforts. The Microscopic Observation Drug Susceptibility
(MODS) assay uses visual recognition of cording patterns from Mycobacterium
tuberculosis (MTB) to diagnose tuberculosis infection and drug susceptibility
directly from a sputum sample in 7-10 days with a low cost. An important
limitation that laboratories in the developing world face in MODS implementation
is the presence of permanent technical staff with expertise in reading MODS. We
developed a pattern recognition algorithm to automatically interpret MODS results
from digital images. The algorithm using image processing, feature extraction and
pattern recognition determined geometrical and illumination features used in an
object-model and a photo-model to classify TB-positive images. 765 MODS digital
photos were processed. The single-object model identified MTB (96.9% sensitivity
and 96.3% specificity) and was able to discriminate non-tuberculous mycobacteria
with a high specificity (97.1% M. avium, 99.1% M. chelonae, and 93.8% M.
kansasii). The photo model identified TB-positive samples with 99.1% sensitivity
and 99.7% specificity. This algorithm is a valuable tool that will enable
automatic remote diagnosis using Internet or cellphone telephony. The use of this
algorithm and its further implementation in a telediagnostics platform will
contribute to both faster TB detection and MDR TB determination leading to an
earlier initiation of appropriate treatment.
PMID- 24358228
TI - Herbaceous forage and selection patterns by ungulates across varying herbivore
assemblages in a South African Savanna.
AB - Herbivores generally have strong structural and compositional effects on
vegetation, which in turn determines the plant forage species available. We
investigated how selected large mammalian herbivore assemblages use and alter
herbaceous vegetation structure and composition in a southern African savanna in
and adjacent to the Kruger National Park, South Africa. We compared mixed and
mono-specific herbivore assemblages of varying density and investigated
similarities in vegetation patterns under wildlife and livestock herbivory. Grass
species composition differed significantly, standing biomass and grass height
were almost twice as high at sites of low density compared to high density mixed
wildlife species. Selection of various grass species by herbivores was positively
correlated with greenness, nutrient content and palatability. Nutrient-rich
Urochloa mosambicensis Hack. and Panicum maximum Jacq. grasses were preferred
forage species, which significantly differed in abundance across sites of varying
grazing pressure. Green grasses growing beneath trees were grazed more frequently
than dry grasses growing in the open. Our results indicate that grazing
herbivores appear to base their grass species preferences on nutrient content
cues and that a characteristic grass species abundance and herb layer structure
can be matched with mammalian herbivory types.
PMID- 24358229
TI - Positive association of coronary calcium detected by computed tomography coronary
angiography with periprocedural myocardial infarction.
AB - BACKGROUND: Periprocedural myocardial infarction (PMI) may occur in approximately
5% to 30% of patients undergoing percutaneous coronary intervention. Whether the
morphology of coronary plaque calcium affects the occurrence of PMI is unknown.
MATERIALS AND METHODS: A total of 616 subjects with stable angina and normal
baseline cardiac troponin I levels who had undergone computed tomography
angiography (CTA) were referred to elective percutaneous coronary intervention.
The morphology of coronary calcium was determined by CTA analysis. PMI was
defined as an elevation in 24-h post-procedural cardiac troponin I levels of > 5
times the upper limit of normal with either symptoms of myocardial ischemia, new
ischemic electrocardiographic changes, or documented complications during the
procedure. Logistic regression was performed to identify the effect of the
morphology of coronary calcium on the occurrence of PMI. RESULTS: According to
the presence or morphology of coronary calcium as shown by CTA, 210 subjects were
grouped in the heavy calcification group, 258 in the mild calcification group, 40
in the spotty calcification group and 108 in the control group. The dissection
rate was significantly higher in the heavy calcification group than in the
control group (7.1 % vs. 1.9%, p = 0.03). The occurrence of PMI in the heavy
calcification group was significantly higher than that in the control group (OR
4.38, 95% CI 1.80-10.65, p = 0.001). After multivariate adjustment, the risk of
PMI still remained significantly higher in the heavy calcification group than in
the control group (OR 4.04, 95% CI 1.50-10.89, p = 0.003). CONCLUSIONS: The
morphology of coronary calcium determined by CTA may help to predict the
subsequent occurrence of PMI. A large amount of coronary calcium may be
predictive of PMI.
PMID- 24358230
TI - Impact of different training modalities on anthropometric and metabolic
characteristics in overweight/obese subjects: a systematic review and network
meta-analysis.
AB - BACKGROUND: The aim of this systematic review of randomized controlled trials was
to compare the effects of aerobic training (AET), resistance training (RT), and
combined aerobic and resistance training (CT) on anthropometric parameters, blood
lipids, and cardiorespiratory fitness in overweight and obese subjects. METHODS:
Electronic searches for randomized controlled trials were performed in MEDLINE,
EMBASE and the Cochrane Trial Register. Inclusion criteria were: Body Mass Index:
>=25 kg/m(2), 19+ years of age, supervised exercise training, and a minimum
intervention period of 8 weeks. Anthropometric outcomes, blood lipids, and
cardiorespiratory fitness parameters were included. Pooled effects were
calculated by inverse-variance random effect pairwise meta-analyses and Bayesian
random effects network meta-analyses. FINDINGS: 15 trials enrolling 741
participants were included in the meta-analysis. Compared to RT, AET resulted in
a significantly more pronounced reduction of body weight [mean differences (MD):
1.15 kg, p = 0.04], waist circumference [MD: -1.10 cm, p = 0.004], and fat mass
[MD: -1.15 kg, p = 0.001] respectively. RT was more effective than AET in
improving lean body mass [MD: 1.26 kg, p<0.00001]. When comparing CT with RT, MD
in change of body weight [MD: -2.03 kg, p<0.0001], waist circumference [MD: -1.57
cm, p = 0.0002], and fat mass [MD: -1.88 kg, p<0.00001] were all in favor of CT.
Results from the network meta-analyses confirmed these findings. CONCLUSION:
Evidence from both pairwise and network meta-analyses suggests that CT is the
most efficacious means to reduce anthropometric outcomes and should be
recommended in the prevention and treatment of overweight, and obesity whenever
possible.
PMID- 24358231
TI - Regulation of neuronal differentiation by proteins associated with nuclear
bodies.
AB - Nuclear bodies are large sub-nuclear structures composed of RNA and protein
molecules. The Survival of Motor Neuron (SMN) protein localizes to Cajal bodies
(CBs) and nuclear gems. Diminished cellular concentration of SMN is associated
with the neurodegenerative disease Spinal Muscular Atrophy (SMA). How nuclear
body architecture and its structural components influence neuronal
differentiation remains elusive. In this study, we analyzed the effects of SMN
and two of its interaction partners in cellular models of neuronal
differentiation. The nuclear 23 kDa isoform of Fibroblast Growth Factor - 2 (FGF
2(23)) is one of these interacting proteins - and was previously observed to
influence nuclear bodies by destabilizing nuclear gems and mobilizing SMN from
Cajal bodies (CBs). Here we demonstrate that FGF-2(23) blocks SMN-promoted
neurite outgrowth, and also show that SMN disrupts FGF-2(23)-dependent
transcription. Our results indicate that FGF-2(23) and SMN form an inactive
complex that interferes with neuronal differentiation by mutually antagonizing
nuclear functions. Coilin is another nuclear SMN binding partner and a marker
protein for Cajal bodies (CBs). In addition, coilin is essential for CB function
in maturation of small nuclear ribonucleoprotein particles (snRNPs). The role of
coilin outside of Cajal bodies and its putative impacts in tissue differentiation
are poorly defined. The present study shows that protein levels of nucleoplasmic
coilin outside of CBs decrease during neuronal differentiation. Overexpression of
coilin has an inhibitory effect on neurite outgrowth. Furthermore, we find that
nucleoplasmic coilin inhibits neurite outgrowth independent of SMN binding
revealing a new function for coilin in neuronal differentiation.
PMID- 24358232
TI - Diffusion MRI and novel texture analysis in osteosarcoma xenotransplants predicts
response to anti-checkpoint therapy.
AB - Combinations of targeted drugs have been employed to treat sarcomas, however,
response rates have not improved notably, therefore emphasizing the need for
novel treatments. In addition, imaging approaches to assess therapeutic response
is lacking, as currently measurable indices, such as volume and/or diameter, do
not accurately correlate with changes in tumor biology. In this study,
quantitative and profound analyses of magnetic resonance imaging (MRI) were
developed to evaluate these as imaging biomarkers for MK1775 and Gem in an
osteosarcoma xenotransplant model at early time-points following treatment.
Notably, we showed that Gem and Gem+MK1775 groups had significantly inhibited
tumor growth by day 4, which was presaged by elevations in mean ADC by 24 hours
post treatment. Significant differences were also observed at later time points
for the Gem+MK1775 combination and MK1775 therapy. ADC distribution and entropy
(randomness of ADC values) were also elevated by 24 hours following therapy.
Immunohistochemistry demonstrated that these treatment-related increases in ADC
correlated with apoptosis and observed cell condensations (dense- and exploded
bodies). These findings underline the role of ADC as a quantitative imaging
biomarker for therapy-induced response and show promising clinical relevance in
the sarcoma patient population.
PMID- 24358233
TI - A Cell Derived Active Contour (CDAC) method for robust tracking in low frame
rate, low contrast phase microscopy - an example: the human hNT astrocyte.
AB - The problem of automated segmenting and tracking of the outlines of cells in
microscope images is the subject of active research. While great progress has
been made on recognizing cells that are of high contrast and of predictable
shape, many situations arise in practice where these properties do not exist and
thus many interesting potential studies - such as the migration patterns of
astrocytes to scratch wounds - have been relegated to being largely qualitative
in nature. Here we analyse a select number of recent developments in this area,
and offer an algorithm based on parametric active contours and formulated by
taking into account cell movement dynamics. This Cell-Derived Active Contour
(CDAC) method is compared with two state-of-the-art segmentation methods for
phase-contrast microscopy. Specifically, we tackle a very difficult segmentation
problem: human astrocytes that are very large, thin, and irregularly-shaped. We
demonstrate quantitatively better results for CDAC as compared to similar
segmentation methods, and we also demonstrate the reliable segmentation of
qualitatively different data sets that were not possible using existing methods.
We believe this new method will enable new and improved automatic cell migration
and movement studies to be made.
PMID- 24358234
TI - Modeling social transmission dynamics of unhealthy behaviors for evaluating
prevention and treatment interventions on childhood obesity.
AB - Research evidence indicates that obesity has spread through social networks, but
lever points for interventions based on overlapping networks are not well
studied. The objective of our research was to construct and parameterize a system
dynamics model of the social transmission of behaviors through adult and youth
influence in order to explore hypotheses and identify plausible lever points for
future childhood obesity intervention research. Our objectives were: (1) to
assess the sensitivity of childhood overweight and obesity prevalence to peer and
adult social transmission rates, and (2) to test the effect of combinations of
prevention and treatment interventions on the prevalence of childhood overweight
and obesity. To address the first objective, we conducted two-way sensitivity
analyses of adult-to-child and child-to-child social transmission in relation to
childhood overweight and obesity prevalence. For the second objective,
alternative combinations of prevention and treatment interventions were tested by
varying model parameters of social transmission and weight loss behavior rates.
Our results indicated child overweight and obesity prevalence might be slightly
more sensitive to the same relative change in the adult-to-child compared to the
child-to-child social transmission rate. In our simulations, alternatives with
treatment alone, compared to prevention alone, reduced the prevalence of
childhood overweight and obesity more after 10 years (1.2-1.8% and 0.2-1.0%
greater reduction when targeted at children and adults respectively). Also, as
the impact of adult interventions on children was increased, the rank of six
alternatives that included adults became better (i.e., resulting in lower 10 year
childhood overweight and obesity prevalence) than alternatives that only involved
children. The findings imply that social transmission dynamics should be
considered when designing both prevention and treatment intervention approaches.
Finally, targeting adults may be more efficient, and research should strengthen
and expand adult-focused interventions that have a high residual impact on
children.
PMID- 24358235
TI - Valproic acid causes proteasomal degradation of DICER and influences miRNA
expression.
AB - Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar
disorders. Known properties of VPA are inhibitions of histone deacetylases and
activation of extracellular signal regulated kinases (ERK), which cannot fully
explain VPA's clinical features. We found that VPA induces the proteasomal
degradation of DICER, a key protein in the generation of micro RNAs.
Unexpectedly, the concentration of several micro RNAs increases after VPA
treatment, which is caused by the upregulation of their hosting genes prior to
DICER degradation. The data suggest that a loss of DICER protein and changes in
micro RNA concentration contributes to the clinical properties of VPA. VPA can be
used experimentally to down regulate DICER protein levels, which likely reflects
a natural regulation of DICER.
PMID- 24358236
TI - Traumatic brain injury: unmet support needs of caregivers and families in
Florida.
AB - Sustaining a Traumatic Brain Injury results in familial strain due to the
significant impact the injury has upon the role and function of individuals and
their families at home and in the community. Using the Stress Process Model of
Caregiving, a caregiver needs assessment survey was developed and conducted to
better understand the needs of individuals with a Traumatic Brain Injury and
their caregivers. Survey results indicate that caregivers experience many
challenges including unmet needs in areas of relational supports such as
maintaining relationships, long-term emotional and financial support for
themselves and the survivor, and the need for a patient or caregiver advocate.
Implications for future practice are presented.
PMID- 24358237
TI - Quantitative assessment of the association of COX-2 (Cyclooxygenase-2)
immunoexpression with prognosis in human osteosarcoma: a meta-analysis.
AB - BACKGROUND: Numerous studies examining the relationship between Cyclooxygenase-2
(COX-2) immunoexpression and clinical outcome in osteosarcoma patients have
yielded inconclusive results. METHODS: We accordingly conducted a meta-analysis
of 9 studies (442 patients) that evaluated the correlation between COX-2
immunoexpression and clinical prognosis (death). Pooled odds ratios (OR) and risk
ratios (RR) with 95% confidence intervals (95% CI) were calculated using the
random-effects or fixed-effects model. RESULTS: Meta-analysis showed no
significant association between COX-2 positivity and age, gender, tumor location,
histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression
was associated with overall survival rate (RR=2.12; 95% CI: 1.10-3.74; P=0.009)
and disease-free survival rate (RR=1.63; 95% CI: 1.17-2.28; P=0.004) at 2 years.
Sensitivity analysis performed by omitting low quality studies showed that the
pooled results were stable. CONCLUSIONS: COX-2 positivity was associated with a
lower 2-year overall survival rate and disease-free survival rate. COX-2
expression change is an independent prognostic factor in patients with
osteosarcoma.
PMID- 24358238
TI - Differential patterns of prefrontal MEG activation during verbal & visual
encoding and retrieval.
AB - The spatiotemporal profile of activation of the prefrontal cortex in verbal and
non-verbal recognition memory was examined using magnetoencephalography (MEG).
Sixteen neurologically healthy right-handed participants were scanned whilst
carrying out a modified version of the Doors and People Test of recognition
memory. A pattern of significant prefrontal activity was found for non-verbal and
verbal encoding and recognition. During the encoding, verbal stimuli activated an
area in the left ventromedial prefrontal cortex, and non-verbal stimuli activated
an area in the right. A region in the left dorsolateral prefrontal cortex also
showed significant activation during the encoding of non-verbal stimuli. Both
verbal and non-verbal stimuli significantly activated an area in the right
dorsomedial prefrontal cortex and the right anterior prefrontal cortex during
successful recognition, however these areas showed temporally distinct activation
dependent on material, with non-verbal showing activation earlier than verbal
stimuli. Additionally, non-verbal material activated an area in the left anterior
prefrontal cortex during recognition. These findings suggest a material-specific
laterality in the ventromedial prefrontal cortex during encoding for verbal and
non-verbal but also support the HERA model for verbal material. The discovery of
two process dependent areas during recognition that showed patterns of temporal
activation dependent on material demonstrates the need for the application of
more temporally sensitive techniques to the involvement of the prefrontal cortex
in recognition memory.
PMID- 24358239
TI - Men at risk; a qualitative study on HIV risk, gender identity and violence among
men who have sex with men who report high risk behavior in Kampala, Uganda.
AB - In Uganda, men who have sex with men (MSM) are at high risk for HIV. Between May
2008 and February 2009 in Kampala, Uganda, we used respondent driven sampling
(RDS) to recruit 295 MSM>=18 years who reported having had sex with another man
in the preceding three months. The parent study conducted HIV and STI testing and
collected demographic and HIV-related behavioral data through audio computer
assisted self-administered interviews. We conducted a nested qualitative sub
study with 16 men purposively sampled from among the survey participants based on
responses to behavioral variables indicating higher risk for HIV infection. Sub
study participants were interviewed face-to-face. Domains of inquiry included
sexual orientation, gender identity, condom use, stigma, discrimination, violence
and health seeking behavior. Emergent themes included a description of sexual
orientation/gender identity categories. All groups of men described conflicting
feelings related to their sexual orientation and contextual issues that do not
accept same-sex identities or behaviors and non-normative gender presentation.
The emerging domains for facilitating condom use included: lack of trust in
partner and fear of HIV infection. We discuss themes in the context of social and
policy issues surrounding homosexuality and HIV prevention in Uganda that
directly affect men's lives, risk and health-promoting behaviors.
PMID- 24358240
TI - Impacts of ocean acidification on early life-history stages and settlement of the
coral-eating sea star Acanthaster planci.
AB - Coral reefs are marine biodiversity hotspots, but their existence is threatened
by global change and local pressures such as land-runoff and overfishing.
Population explosions of coral-eating crown of thorns sea stars (COTS) are a
major contributor to recent decline in coral cover on the Great Barrier Reef.
Here, we investigate how projected near-future ocean acidification (OA)
conditions can affect early life history stages of COTS, by investigating
important milestones including sperm motility, fertilisation rates, and larval
development and settlement. OA (increased pCO2 to 900-1200 uatm pCO2)
significantly reduced sperm motility and, to a lesser extent, velocity, which
strongly reduced fertilization rates at environmentally relevant sperm
concentrations. Normal development of 10 d old larvae was significantly lower
under elevated pCO2 but larval size was not significantly different between
treatments. Settlement of COTS larvae was significantly reduced on crustose
coralline algae (known settlement inducers of COTS) that had been exposed to OA
conditions for 85 d prior to settlement assays. Effect size analyses illustrated
that reduced settlement may be the largest bottleneck for overall juvenile
production. Results indicate that reductions in fertilisation and settlement
success alone would reduce COTS population replenishment by over 50%. However, it
is unlikely that this effect is sufficient to provide respite for corals from
other negative anthropogenic impacts and direct stress from OA and warming on
corals.
PMID- 24358241
TI - The impacts of dispositional optimism and psychological resilience on the
subjective well-being of burn patients: a structural equation modelling analysis.
AB - Burn wounds are severely stressful events that can have a significant impact on
the mental health of patients. However, the impact of burns on individuals with
different personality traits can be different. The present study aimed to
investigate the impact of dispositional optimism on the subjective well-being of
burn patients, and mainly focused on the confirmation of the mediator role of
psychological resilience. 410 burn patients from five general hospitals in Xi'an
accomplished the revised Life Orientation Test, Connor-Davidson Resilience Scale,
and Subjective Well-Being (SWB) scale. The results revealed that both
dispositional optimism and psychological resilience were significantly correlated
with SWB. Structural equation modelling indicated that psychological resilience
partially mediated the relationship between dispositional optimism and SWB. The
current findings extended prior reports and shed some light on how dispositional
optimism influenced SWB. Limitations of the study were considered and suggestions
for future studies were also discussed.
PMID- 24358242
TI - Confronting the paradox of enrichment to the metacommunity perspective.
AB - Resource enrichment can potentially destabilize predator-prey dynamics. This
phenomenon historically referred as the "paradox of enrichment" has mostly been
explored in spatially homogenous environments. However, many predator-prey
communities exchange organisms within spatially heterogeneous networks called
metacommunities. This heterogeneity can result from uneven distribution of
resources among communities and thus can lead to the spreading of local
enrichment within metacommunities. Here, we adapted the original Rosenzweig
MacArthur predator-prey model, built to study the paradox of enrichment, to
investigate the effect of regional enrichment and of its spatial distribution on
predator-prey dynamics in metacommunities. We found that the potential for
destabilization was depending on the connectivity among communities and the
spatial distribution of enrichment. In one hand, we found that at low dispersal
regional enrichment led to the destabilization of predator-prey dynamics. This
destabilizing effect was more pronounced when the enrichment was uneven among
communities. In the other hand, we found that high dispersal could stabilize the
predator-prey dynamics when the enrichment was spatially heterogeneous. Our
results illustrate that the destabilizing effect of enrichment can be dampened
when the spatial scale of resource enrichment is lower than that of organismss
movements (heterogeneous enrichment). From a conservation perspective, our
results illustrate that spatial heterogeneity could decrease the regional
extinction risk of species involved in specialized trophic interactions. From the
perspective of biological control, our results show that the heterogeneous
distribution of pest resource could favor or dampen outbreaks of pests and of
their natural enemies, depending on the spatial scale of heterogeneity.
PMID- 24358243
TI - Rapid determination of oxygen saturation and vascularity for cancer detection.
AB - A rapid heuristic ratiometric analysis for estimating tissue hemoglobin
concentration and oxygen saturation from measured tissue diffuse reflectance
spectra is presented. The analysis was validated in tissue-mimicking phantoms and
applied to clinical measurements in head and neck, cervical and breast tissues.
The analysis works in two steps. First, a linear equation that translates the
ratio of the diffuse reflectance at 584 nm and 545 nm to estimate the tissue
hemoglobin concentration using a Monte Carlo-based lookup table was developed.
This equation is independent of tissue scattering and oxygen saturation. Second,
the oxygen saturation was estimated using non-linear logistic equations that
translate the ratio of the diffuse reflectance spectra at 539 nm to 545 nm into
the tissue oxygen saturation. Correlations coefficients of 0.89 (0.86), 0.77
(0.71) and 0.69 (0.43) were obtained for the tissue hemoglobin concentration
(oxygen saturation) values extracted using the full spectral Monte Carlo and the
ratiometric analysis, for clinical measurements in head and neck, breast and
cervical tissues, respectively. The ratiometric analysis was more than 4000 times
faster than the inverse Monte Carlo analysis for estimating tissue hemoglobin
concentration and oxygen saturation in simulated phantom experiments. In
addition, the discriminatory power of the two analyses was similar. These results
show the potential of such empirical tools to rapidly estimate tissue hemoglobin
in real-time spectral imaging applications.
PMID- 24358244
TI - Cell death induced on cell cultures and nude mouse skin by non-thermal,
nanosecond-pulsed generated plasma.
AB - Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited
species with a small proportion of ions and energetic electrons. Non-thermal
plasmas can be generated with any high electro-magnetic field. We studied here
the pathological effects, and in particular cell death, induced by nanosecond
pulsed high voltage generated plasmas homogeneously applied on cell cultures and
nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and
necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death
occurred for doses above 113 J/cm(2) for the epidermis, 281 J/cm(2) for the
dermis, and 394 J/cm(2) for the hypodermis. Using electron microscopy, we
characterized apoptosis for low doses and necrosis for high doses. We
demonstrated that these effects were not related to thermal, photonic or pH
variations, and were due to the production of free radicals. The ability of cold
plasmas to generate apoptosis on cells in suspension and, without any sensitizer,
on precise skin areas, opens new fields of application in dermatology for
extracorporeal blood cell treatment and the eradication of superficial skin
lesions.
PMID- 24358245
TI - Serotonin is a key factor for mouse red blood cell survival.
AB - Serotonin (5-HT) is a monoamine originally purified from blood as a vasoactive
agent. In nonneuronal tissues, its presence is linked with the expression of
tryptophan hydroxylase 1 (TPH1) that catalyzes the rate-limiting step of its
synthesis. Targeted disruption in mice of the TPH1 gene results in very low
levels of circulating 5-HT. Previous analysis of the TPH1 knockout (TPH1(-/-))
mouse revealed that they develop a phenotype of macrocytic anemia with a reduced
half-life of their circulating red blood cells (RBC). In this study, to establish
whether the observed reduced half-life of TPH1(-/-) RBC is an intrinsic or an
extrinsic characteristic, we compared their survival to RBC isolated from wild
type mice. Both in vivo and in vitro data converge to demonstrate an extrinsic
protective effect of 5-HT since presence of 5-HT in the RBC environment protects
RBC from senescence. The protective effect played by 5-HT is not mediated through
activation of a classical pharmacological pathway as no 5-HT receptors were
detected on isolated RBC. Rather, 5-HT acts as an effective antioxidant since
reduction of 5-HT circulating levels are associated with a decrease in the plasma
antioxidant capacity. We further demonstrate a link between oxidation and the
removal of damaged RBC following transfusion, as supplementation with 5-HT
improves RBC post-transfusion survival in a mouse model of blood banking.
PMID- 24358246
TI - Reference genes selection for quantitative real-time PCR using RankAggreg method
in different tissues of Capra hircus.
AB - Identification of reference genes with stable levels of gene expression is an
important prerequisite for obtaining reliable results in analysis of gene
expression data using quantitative real time PCR (RT-qPCR). Since the underlying
assumption of reference genes is that expressed at the exact same level in all
sample types, in this study, we evaluated the expression stability of nine most
commonly used endogenous controls (GAPDH, ACTB, 18S rRNA, RPS18, HSP-90, ALAS,
HMBS, ACAC, and B2M) in four different tissues of the domestic goat, Capra
hircus, including liver, visceral, subcutaneous fat and longissimus muscles,
across different experimental treatments (a standard diet prepared using the NRC
computer software as control and the same diet plus one mg chromium/day). We used
six different software programs for ranking of reference genes and found that
individual rankings of the genes differed among them. Additionally, there was a
significant difference in ranking patterns of the studied genes among different
tissues. A rank aggregation method was applied to combine the ranking lists of
the six programs to a consensus ranking. Our results revealed that HSP-90 was
nearly always among the two most stable genes in all studied tissues. Therefore,
it is recommended for accurate normalization of RT-qPCR data in goats, while
GAPDH, ACTB, and RPS18 showed the most varied expressions and should be avoided
as reference genes.
PMID- 24358247
TI - Distribution of endophytic bacteria in Alopecurus aequalis Sobol and Oxalis
corniculata L. from soils contaminated by polycyclic aromatic hydrocarbons.
AB - The distributions of endophytic bacteria in Alopecurus aequalis Sobol and Oxalis
corniculata L. grown in soils contaminated with different levels of polycyclic
aromatic hydrocarbons (PAHs) were investigated with polymerase chain reaction
followed by denaturing gradient gel electrophoresis technology (PCR-DGGE) and
cultivation methods. Twelve types of PAHs, at concentrations varying from 0.16 to
180 mg.kg(-1), were observed in the roots and shoots of the two plants. The total
PAH concentrations in Alopecurus aequalis Sobol obtained from three different PAH
contaminated stations were 184, 197, and 304 mg.kg(-1), and the total PAH
concentrations in Oxalis corniculata L. were 251, 346, and 600 mg.kg(-1),
respectively. The PCR-DGGE results showed that the endophytic bacterial
communities in the roots and shoots of the two plants were quite different,
although most bacteria belonged to Firmicutes, Proteobacteria, Actinobacteria and
Bacteroidetes. A total of 68 endophytic bacterial strains were isolated from
different tissues of the two plants and classified into three phyla: Firmicutes,
Proteobacteria and Bacteroidetes. In both plants, Bacillus spp. and Pseudomonas
spp. were the dominant cultivable populations. With an increase in the PAH
pollution level, the diversity and distribution of endophytic bacteria in the two
plants changed correspondingly, and the number of cultivable endophytic bacterial
strains decreased rapidly. Testing of the isolated endophytic bacteria for
tolerance to each type of PAH showed that most isolates could grow well on Luria
Bertani media in the presence of different PAHs, and some isolates were able to
grow rapidly on a mineral salt medium with a single PAH as the sole carbon and
energy source, indicating that these strains may have the potential to degrade
PAHs in plants. This research provides the first insight into the characteristics
of endophytic bacterial populations under different PAH pollution levels and
provides a species resource for the isolation of PAH-degrading endophytic
bacteria.
PMID- 24358248
TI - A robust model-free approach for rare variants association studies incorporating
gene-gene and gene-environmental interactions.
AB - Recently more and more evidence suggest that rare variants with much lower minor
allele frequencies play significant roles in disease etiology. Advances in next
generation sequencing technologies will lead to many more rare variants
association studies. Several statistical methods have been proposed to assess the
effect of rare variants by aggregating information from multiple loci across a
genetic region and testing the association between the phenotype and aggregated
genotype. One limitation of existing methods is that they only look into the
marginal effects of rare variants but do not systematically take into account
effects due to interactions among rare variants and between rare variants and
environmental factors. In this article, we propose the summation of partition
approach (SPA), a robust model-free method that is designed specifically for
detecting both marginal effects and effects due to gene-gene (G*G) and gene
environmental (G*E) interactions for rare variants association studies. SPA has
three advantages. First, it accounts for the interaction information and gains
considerable power in the presence of unknown and complicated G*G or G*E
interactions. Secondly, it does not sacrifice the marginal detection power; in
the situation when rare variants only have marginal effects it is comparable with
the most competitive method in current literature. Thirdly, it is easy to extend
and can incorporate more complex interactions; other practitioners and scientists
can tailor the procedure to fit their own study friendly. Our simulation studies
show that SPA is considerably more powerful than many existing methods in the
presence of G*G and G*E interactions.
PMID- 24358249
TI - Disparities and trends in indoor exposure to secondhand smoke among U.S.
adolescents: 2000-2009.
AB - INTRODUCTION: Secondhand smoke (SHS) exposure causes disease and death among
nonsmokers. With a plethora of smoke-free legislation implemented and a steady
decrease in cigarette consumption noted over the past decade in the U.S., this
study assessed trends in indoor SHS exposure among U.S. adolescents in grades 6
12 during 2000-2009. METHODS: Data were obtained from the 2000-2009 National
Youth Tobacco Survey - a national survey of U.S. middle and high school students.
SHS exposure within an indoor area within the past seven days was self-reported.
Trends in indoor SHS exposure during 2000-2009 were assessed overall and by socio
demographic characteristics, using the Wald's test in a binary logistic
regression. Within-group comparisons were performed using chi-squared statistics
(p<0.05). RESULTS: The proportion of U.S. middle and high school students who
were exposed to indoor SHS declined from 65.5% in 2000 to 40.5% in 2009 (p<0.05
for linear trend). Significant declines were also observed across all population
subgroups. Between 2000 and 2009, prevalence of indoor SHS exposure declined
significantly among both middle (58.5% to 34.3%) and high school (71.5% to 45.4%)
students. Prevalence of indoor SHS exposure was significantly higher among girls
(44.0% in 2009) compared to boys (37.2% in 2009) during each survey year.
Similarly, prevalence of indoor SHS exposure during 2000-2009 was highest among
non-Hispanic whites (44.2% in 2009) and lowest among non-Hispanic Asians (30.2%
in 2009). During each survey year, prevalence was highest among the oldest age
group (>=18 years) and lowest among the youngest (9-11 years). Also, prevalence
was significantly higher among current cigarette smokers (83.8% in 2009) compared
to nonsmokers (34.0% in 2009). CONCLUSION: Significant declines in indoor SHS
exposure among U.S. middle and high school students occurred during 2000-2009.
While the results are encouraging, additional efforts are needed to further
reduce youth indoor SHS exposure.
PMID- 24358250
TI - Shifts in climate foster exceptional opportunities for species radiation: the
case of South african geraniums.
AB - Climate change is often assumed to be a major driver of biodiversity loss.
However, it can also set the stage for novel diversification in lineages with the
evolutionary ability to colonize new environments. Here we tested if the
extraordinary evolutionary success of the genus Pelargonium was related to the
ability of its species to capitalize on the climate niche variation produced by
the historical changes in southern Africa. We evaluated the relationship between
rates of climate niche evolution and diversification rates in the main
Pelargonium lineages and disentangled the roles of deep and recent historical
events in the modification of species niches. Pelargonium clades exhibiting
higher ecological differentiation along summer precipitation (SPP) gradients also
experienced higher diversification rates. Faster rates of niche differentiation
in spatially structured variables, along with lower levels of niche overlap among
closely related species, suggest recent modification in species niches (e.g.
dispersal or range shift) and niche lability. We suggest that highly structured
SPP gradients established during the aridification process within southern
Africa, in concert with niche lability and low niche overlap, contributed to
species divergence. These factors are likely to be responsible for the extensive
diversification of other lineages in this diversity hot spot.
PMID- 24358251
TI - Lysophosphatidylcholine and carotid intima-media thickness in young smokers: a
role for oxidized LDL-induced expression of PBMC lipoprotein-associated
phospholipase A2?
AB - BACKGROUND: Although cigarette smoking has been associated with carotid intima
media thickness (CIMT) the mechanisms are yet not completely known.
Lysophosphatidylcholine (lysoPC), a main product of lipoprotein-associated
phospholipase A2 (Lp-PLA2) activity, appears to be a major determinant of the pro
atherogenic properties of oxidized LDL (oxLDL) and to induce proteoglycan
synthesis, a main player in intimal thickening. In this study we assessed whether
cigarette smoking-induced oxidative stress may influence plasma Lp-PLA2 and
lysoPC and Lp-PLA2 expression in peripheral blood mononuclear cells (PBMC), as
well as the relationship between lysoPC and CIMT. METHODS/RESULTS: 45 healthy
smokers and 45 age and sex-matched subjects participated in this study. Smokers,
compared to non-smokers, showed increased plasma concentrations of oxLDL, Lp-PLA2
and lysoPC together with up-regulation of Lp-PLA2 (mRNA and protein) expression
in PBMC (P<0.001). Plasma Lp-PLA2 positively correlated with both lysoPC
(r=0.639, P<0.001) and PBMC mRNA Lp-PLA2 (r=0.484, P<0.001) in all subjects.
Moreover CIMT that was higher in smokers (P<0.001), positively correlated with
lysoPC (r=0.55, P<0.001). Then in in vitro study we demonstrated that both oxLDL
(at concentrations similar to those found in smoker's serum) and oxidized
phospholipids contained in oxLDL, were able to up-regulate mRNA Lp-PLA2 in PBMC.
This effect was likely due, at least in part, to the enrichment in oxidized
phospholipids found in PBMC after exposure to oxLDL. Our results also showed that
in human aortic smooth muscle cells lysoPC, at concentrations similar to those
found in smokers, increased the expression of biglycan and versican, two main
proteoglycans. CONCLUSIONS: In smokers a further effect of raised oxidative
stress is the up-regulation of Lp-PLA2 expression in PBMC with subsequent
increase of plasma Lp-PLA2 and lysoPC. Moreover the correlation between lysoPC
and CIMT together with the finding that lysoPC up-regulates proteoglycan
synthesis suggests that lysoPC may be a link between smoking and intimal
thickening.
PMID- 24358252
TI - The association between the serum C-peptide level and bone mineral density.
AB - OBJECTIVE: Although serum C-peptide was previously considered biologically
inactive, a growing number of recent studies have shown that it is an active
peptide with important physiologic functions. The present study aimed to
investigate the association of serum C-peptide level with bone mineral density
(BMD) in residents of the United States. METHODS: The study included 6,625
participants aged 12-85 years. Total and regional BMD were measured using dual
energy X-ray absorptiometry. Stratified multiple linear regression analysis was
performed to determine the association of the serum C-peptide level with BMD.
Three regression models were produced for each stratum. All models were adjusted
for ethnicity, height, weight, education level, physical activity, smoking
status, alcohol use, triglycerides and creatinine level, and models 2 and 3 were
further adjusted for the fasting plasma glucose (FPG) and alkaline phosphatase
(ALP) levels, respectively. RESULTS: Sex-specific results showed a significant
association between the serum C-peptide level and total BMD in both sexes.
Stratified analyses based on age and body mass index showed that serum C-peptide
levels were significantly negatively associated with most regional BMD, and most
of these associations remained significant after stratification based on the
serum insulin level. CONCLUSION: The serum C-peptide level was significantly
negatively associated with the total and most regional BMD. These findings
suggest that serum C-peptide may have biological activity associated with bone
metabolism and therefore serum C-peptide control is advisable in order to reduce
the risk of low bone mineral density.
PMID- 24358253
TI - The impact of ocean acidification on the functional morphology of foraminifera.
AB - Culturing experiments were performed on sediment samples from the Ythan Estuary,
N. E. Scotland, to assess the impacts of ocean acidification on test surface
ornamentation in the benthic foraminifer Haynesina germanica. Specimens were
cultured for 36 weeks at either 380, 750 or 1000 ppm atmospheric CO2. Analysis of
the test surface using SEM imaging reveals sensitivity of functionally important
ornamentation associated with feeding to changing seawater CO2 levels. Specimens
incubated at high CO2 levels displayed evidence of shell dissolution, a
significant reduction and deformation of ornamentation. It is clear that these
calcifying organisms are likely to be vulnerable to ocean acidification. A
reduction in functionally important ornamentation could lead to a reduction in
feeding efficiency with consequent impacts on this organism's survival and
fitness.
PMID- 24358255
TI - Selective injection system into hippocampus CA1 via monitored theta oscillation.
AB - Methods of cell biology and electrophysiology using dissociated primary cultured
neurons allow in vitro study of molecular functions; however, analysis of intact
neuronal circuitry is often preferable. To investigate exogenous genes, viral
vectors are most commonly injected using a pipette that is inserted from the top
of the cortex. Although there are few reports that describe the success rate of
injection in detail, it is sometimes difficult to locate the pipette tip
accurately within the CA1 pyramidal cell layer because the pyramidal layer is
only 0.1 mm thick. In the present study, we have developed a system to inject
viral vectors accurately into the mouse hippocampal CA1 pyramidal cell layer
using a stereotaxic injection system with simultaneous electrophysiological
monitoring of theta oscillation. The pipette tip was positioned reliably based on
integrated values of the theta oscillation in the hippocampal CA1 pyramidal cell
layer. This approach allows accurate injection of solutions and provides an
efficient method of gene transfer using viral vectors into the hippocampus, which
can be a useful tool for studies involving the molecular mechanisms of neuronal
functions.
PMID- 24358254
TI - Microbial ecology of the hive and pollination landscape: bacterial associates
from floral nectar, the alimentary tract and stored food of honey bees (Apis
mellifera).
AB - Nearly all eukaryotes are host to beneficial or benign bacteria in their gut
lumen, either vertically inherited, or acquired from the environment. While
bacteria core to the honey bee gut are becoming evident, the influence of the
hive and pollination environment on honey bee microbial health is largely
unexplored. Here we compare bacteria from floral nectar in the immediate
pollination environment, different segments of the honey bee (Apis mellifera)
alimentary tract, and food stored in the hive (honey and packed pollen or
"beebread"). We used cultivation and sequencing to explore bacterial communities
in all sample types, coupled with culture-independent analysis of beebread. We
compare our results from the alimentary tract with both culture-dependent and
culture-independent analyses from previous studies. Culturing the foregut (crop),
midgut and hindgut with standard media produced many identical or highly similar
16S rDNA sequences found with 16S rDNA clone libraries and next generation
sequencing of 16S rDNA amplicons. Despite extensive culturing with identical
media, our results do not support the core crop bacterial community hypothesized
by recent studies. We cultured a wide variety of bacterial strains from 6 of 7
phylogenetic groups considered core to the honey bee hindgut. Our results reveal
that many bacteria prevalent in beebread and the crop are also found in floral
nectar, suggesting frequent horizontal transmission. From beebread we uncovered a
variety of bacterial phylotypes, including many possible pathogens and food
spoilage organisms, and potentially beneficial bacteria including Lactobacillus
kunkeei, Acetobacteraceae and many different groups of Actinobacteria.
Contributions of these bacteria to colony health may include general hygiene,
fungal and pathogen inhibition and beebread preservation. Our results are
important for understanding the contribution to pollinator health of both
environmentally vectored and core microbiota, and the identification of factors
that may affect bacterial detection and transmission, colony food storage and
disease susceptibility.
PMID- 24358257
TI - Highly-sensitive allele-specific PCR testing identifies a greater prevalence of
transmitted HIV drug resistance in Japan.
AB - BACKGROUND: The transmission of drug-resistant HIV in newly identified infected
populations has become an underlying epidemic which can be better assessed with
sensitive resistance testing. Since minority drug resistant variants cannot be
detected by bulk sequencing, methods with improved sensitivity are required.
Thus, the goal of this study was to evaluate if transmitted drug resistance
mutations at minority levels in Japanese patients could be identified using
highly sensitive allele-specific PCR (AS-PCR). MATERIALS AND METHODS: Samples
were taken from newly diagnosed HIV/AIDS cases at the National Nagoya Hospital
from January 2008 to December 2009. All samples were bulk sequenced for HIV
protease and reverse transcriptase. To detect minority populations with drug
resistance, we used AS-PCR with mutation-specific primers designed for seven
reverse transcriptase inhibitor resistance mutations, M41L, K65R, K70R, K103N,
Y181C, M184V, and T215F/Y, and for three protease inhibitor resistance mutations,
M46I/L and L90M. RESULTS: We studied 149 newly identified HIV cases. Bulk
sequencing detected 8 cases with NRTI resistance mutations (one with A62V, one
D67E, one T215D, one T215E, two with T215L and two T215S) and 15 with PI
resistance mutations (one with N88D and 14 with M46I). Results obtained by AS-PCR
and bulk sequencing demonstrated good concordance but the AS-PCR enabled the
detection of seven additional drug-resistant cases (one M41L, two with K65R, two
with K70R, and one M184V) in the RT region. Additionally, AS-PCR assays
identified 15 additional cases with M46I, five with M46L and four cases with L90M
in the protease region. CONCLUSIONS: Using AS-PCR substantially increased the
detection of transmitted drug resistance in this population from 15.4% to 26.8%,
further supporting the benefit of sensitive testing among drug-naive populations.
Since the clinical impact of minority drug-resistant populations is not fully
comprehended for all mutations, follow-up studies are needed to understand their
significance for treatment.
PMID- 24358256
TI - Soluble products of Escherichia coli induce mitochondrial dysfunction-related
sperm membrane lipid peroxidation which is prevented by lactobacilli.
AB - Unidentified soluble factors secreted by E. coli, a frequently isolated
microorganism in genitourinary infections, have been reported to inhibit
mitochondrial membrane potential (DeltaPsim), motility and vitality of human
spermatozoa. Here we explore the mechanisms involved in the adverse impact of E.
coli on sperm motility, focusing mainly on sperm mitochondrial function and
possible membrane damage induced by mitochondrial-generated reactive oxygen
species (ROS). Furthermore, as lactobacilli, which dominate the vaginal ecosystem
of healthy women, have been shown to exert anti-oxidant protective effects on
spermatozoa, we also evaluated whether soluble products from these microorganisms
could protect spermatozoa against the effects of E. coli. We assessed motility
(by computer-aided semen analysis), DeltaPsim (with JC-1 dye by flow cytometry),
mitochondrial ROS generation (with MitoSOX red dye by flow cytometry) and
membrane lipid-peroxidation (with the fluorophore BODIPY C11 by flow cytometry)
of sperm suspensions exposed to E. coli in the presence and in the absence of a
combination of 3 selected strains of lactobacilli (L. brevis, L. salivarius, L.
plantarum). A Transwell system was used to avoid direct contact between
spermatozoa and microorganisms. Soluble products of E. coli induced DeltaPsim
loss, mitochondrial generation of ROS and membrane lipid-peroxidation, resulting
in motility loss. Soluble factors of lactobacilli prevented membrane lipid
peroxidation of E. coli-exposed spermatozoa, thus preserving their motility. In
conclusion, sperm motility loss by soluble products of E. coli reflects a
mitochondrial dysfunction-related membrane lipid-peroxidation. Lactobacilli could
protect spermatozoa in the presence of vaginal disorders, by preventing ROS
induced membrane damage.
PMID- 24358258
TI - From puffins to plankton: a DNA-based analysis of a seabird food chain in the
northern Gulf of Maine.
AB - The predator-prey interactions within food chains are used to both characterize
and understand ecosystems. Conventional methods of constructing food chains from
visual identification of prey in predator diet can suffer from poor taxonomic
resolution, misidentification, and bias against small or completely digestible
prey. Next-generation sequencing (NGS) technology has become a powerful tool for
diet reconstruction through barcoding of DNA in stomach content or fecal samples.
Here we use multi-locus (16S and CO1) next-generation sequencing of DNA barcodes
on the feces of Atlantic puffin (Fratercula arctica) chicks (n=65) and adults
(n=64) and the stomach contents of their main prey, Atlantic herring (Clupea
harengus, n=44) to investigate a previously studied food chain. We compared
conventional and molecular-derived chick diet, tested the similarity between the
diets of puffin adults and chicks, and determined whether herring prey can be
detected in puffin diet samples. There was high variability in the coverage of
prey groups between 16S and CO1 markers. We identified more unique prey with our
16S compared to CO1 barcoding markers (51 and 39 taxa respectively) with only 12
taxa identified by both genes. We found no significant difference between the 16S
identified diets of puffin adults (n=17) and chicks (n=41). Our molecular method
is more taxonomically resolved and detected chick prey at higher frequencies than
conventional field observations. Many likely planktonic prey of herring were
detected in feces from puffin adults and chicks, highlighting the impact
secondary consumption may have on the interpretation of molecular dietary
analysis. This study represents the first simultaneous molecular investigation
into the diet of multiple components of a food chain and highlights the utility
of a multi-locus approach to diet reconstruction that is broadly applicable to
food web analysis.
PMID- 24358259
TI - Probiotic supplementation promotes calcification in Danio rerio larvae: a
molecular study.
AB - A growing number of studies have been showing that dietary probiotics can exert
beneficial health effects in both humans and animals. We previously demonstrated
that dietary supplementation with Lactobacillus rhamnosus - a component of the
human gut microflora - enhances reproduction, larval development, and the
biomineralization process in Danio rerio (zebrafish). The aim of this study was
to identify the pathways affected by L. rhamnosus during zebrafish larval
development. Our morphological and histochemical findings show that L. rhamnosus
accelerates bone deposition through stimulation of the expression of key genes
involved in ossification, e.g. runt-related transcription factor 2 (runx2), Sp7
transcription factor (sp7), matrix Gla protein (mgp), and bone gamma
carboxyglutamate (gla) protein (bglap) as well as through inhibition of
sclerostin (sost), a bone formation inhibitor. Western blot analysis of mitogen
activated protein kinase 1 and 3-(Mapk1 and Mapk3), which are involved in
osteoblast and osteocyte differentiation, documented an increase in Mapk1 16 days
post fertilization (dpf) and of Mapk3 23 dpf in individuals receiving L.
rhamnosus supplementation. Interestingly, a reduction of sost detected in the
same individuals suggests that the probiotic may help treat bone disorders.
PMID- 24358260
TI - Immunization with a thermostable newcastle disease virus K148/08 strain
originated from wild mallard duck confers protection against lethal viscerotropic
velogenic newcastle disease virus infection in chickens.
AB - Newcastle disease (ND) is one of the most devastating poultry infections because
of its worldwide distribution and accompanying economical threat. In the present
study, we characterized the ND virus (NDV) K148/08 strain from wild mallard duck,
with regard to safety, thermostability, immunogenicity, and protective efficacy
against velogenic ND viral infection. The NDV K148/08 strain offered enhanced
immunogenicity and safety relative to commercially available vaccine strains. The
NDV K148/08 strain was safe in 1-day-old SPF chicks after vaccination using a
coarse or cabinet-type fine sprayer. We demonstrated that the NDV K148/08 strain
elicited high levels of antibody responses and provided protective efficacy
against lethal NDV challenge. In addition, the thermostability of the NDV K148/08
strain was as high as that of the thermostable V4 strain. Therefore, the NDV
K148/08 strain may be useful to ensure NDV vaccine performance and effectiveness
in developing countries, especially in remote areas without cold chains.
PMID- 24358261
TI - Seroprevalence and potential risk factors for Brucella spp. infection in
traditional cattle, sheep and goats reared in urban, periurban and rural areas of
Niger.
AB - INTRODUCTION: In Niamey, Niger, interactions within the interface between
animals, humans and the environment induce a potential risk of brucellosis
transmission between animals and from animals to humans. Currently, little is
known about the transmission of Brucella in this context. RESULTS: 5,192 animals
from 681 herds were included in the study. Serum samples and hygroma fluids were
collected. A household survey enabled to identify the risk factors for
transmission of brucellosis. The true adjusted herd-level prevalence of
brucellosis ranged between 11.2% and 17.2% and the true adjusted animal
population level prevalence was 1.3% (95% CI: 0.9-1.8%) based on indirect ELISA
test for Brucella antibodies. Animals aged of 1-4 years were found to be more
susceptible than animals less than 1 year old (Odds ratio [OR] of 2.7; 95% CI:
1.43-5.28). For cattle, the odds of brucellosis seropositivity were higher in
rural compared to the periurban areas (OR of 2.8; 95% CI: 1.48-5.17) whereas for
small ruminants the risk of seropositivity appeared to be higher in urban
compared to periurban areas (OR of 5.5; 95% CI: 1.48-20.38). At herd level, the
risk of transmission was increased by transhumance (OR of 5.4; 95% CI: 2.84
10.41), the occurrence of abortions (OR of 3.0; 95% CI: 1.40-6.41), and for herds
having more than 50 animals (OR of 11.0; 95% CI: 3.75-32.46). Brucella abortus
biovar 3 was isolated from the hygromas. CONCLUSION: brucellosis in Niger is a
serious problem among cattle especially in the rural areas around Niamey and
among sheep in the urban areas of Niamey. The seroprevalence varies across strata
and animal species with important risk factors including herd size, abortion and
transhumance at herd level and age at animal population level. For effective
control of brucellosis, an integrated approach seems appropriate involving all
stakeholders working in public and animal health.
PMID- 24358262
TI - Sequence divergence and conservation in genomes of Helicobacter cetorum strains
from a dolphin and a whale.
AB - BACKGROUND AND OBJECTIVES: Strains of Helicobacter cetorum have been cultured
from several marine mammals and have been found to be closely related in 16 S
rDNA sequence to the human gastric pathogen H. pylori, but their genomes were not
characterized further. METHODS: The genomes of H. cetorum strains from a dolphin
and a whale were sequenced completely using 454 technology and PCR and capillary
sequencing. RESULTS: These genomes are 1.8 and 1.95 mb in size, some 7-26% larger
than H. pylori genomes, and differ markedly from one another in gene content, and
sequences and arrangements of shared genes. However, each strain is more related
overall to H. pylori and its descendant H. acinonychis than to other known
species. These H. cetorum strains lack cag pathogenicity islands, but contain
novel alleles of the virulence-associated vacuolating cytotoxin (vacA) gene. Of
particular note are (i) an extra triplet of vacA genes with <=50% protein-level
identity to each other in the 5' two-thirds of the gene needed for host factor
interaction; (ii) divergent sets of outer membrane protein genes; (iii) several
metabolic genes distinct from those of H. pylori; (iv) genes for an iron
cofactored urease related to those of Helicobacter species from terrestrial
carnivores, in addition to genes for a nickel co-factored urease; and (v) members
of the slr multigene family, some of which modulate host responses to infection
and improve Helicobacter growth with mammalian cells. CONCLUSIONS: Our genome
sequence data provide a glimpse into the novelty and great genetic diversity of
marine helicobacters. These data should aid further analyses of microbial genome
diversity and evolution and infection and disease mechanisms in vast and often
fragile ocean ecosystems.
PMID- 24358263
TI - Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in
adipocytes by Kruppel-like factor 15.
AB - Obese states characterized by chronic inflammation are closely linked to the
development of metabolic dysfunction. We identified adipolin/CTRP12 as an insulin
sensitizing and anti-inflammatory adipokine. Although obese conditions down
regulate adipolin expression, its molecular mechanism is largely unknown. Here we
show that the transcriptional regulator Kruppel-like factor (KLF) 15 is involved
in the regulation of adipolin expression in adipocytes. White adipose tissue from
diet-induced obese (DIO) mice showed decreased expression of KLF9 and KLF15 among
several KLFs, which was accompanied by reduced expression of adipolin. In
cultured 3T3L1 adipocytes, treatment with TNFalpha significantly reduced the mRNA
levels of KLF9, KLF15 and adipolin. Adenovirus-mediated overexpression of KLF15
but not KLF9 reversed TNFalpha-induced reduction of adipolin expression in
adipocytes. Conversely, gene targeting ablation of KLF15 attenuated adipolin
expression in adipocytes. Expression of KLF15 but not KLF9 enhanced the promoter
activity of adipolin in HEK293 cells. Pretreatment of 3T3L1 adipocytes with the
JNK inhibitor SP600125, but not p38 MAPK inhibitor SB203580 blocked the
inhibitory effects of TNFalpha on adipolin and KLF15 expression. These data
suggest that adipose inflammation under conditions of obesity suppresses adipolin
expression via JNK-dependent down-regulation of KLF15 in adipocytes.
PMID- 24358264
TI - Human health risk of ingested nanoparticles that are added as multifunctional
agents to paints: an in vitro study.
AB - Microorganisms growing on painted surfaces are not only an aesthetic problem, but
also actively contribute to the weathering and deterioration of materials. A
widely used strategy to combat microbial colonization is the addition of biocides
to the paint. However, ecotoxic, non-degradable biocides with a broad protection
range are now prohibited in Europe, so the paint industry is considering
engineered nanoparticles (ENPs) as an alternative biocide. There is concern that
ENPs in paint might be released in run-off water and subsequently consumed by
animals and/or humans, potentially coming into contact with cells of the
gastrointestinal tract and affecting the immune system. Therefore, in the present
study we evaluated the cytotoxic effects of three ENPs (nanosilver, nanotitanium
dioxide and nanosilicon dioxide) that have a realistic potential for use in
paints in the near future. When exposed to nanotitanium dioxide and nanosilicon
dioxide in concentrations up to 243 ug/mL for 48 h, neither the gastrointestinal
cells (CaCo-2) nor immune system cells (Jurkat) were significantly affected.
However, when exposed to nanosilver, several cell parameters were affected, but
far less than by silver ions used as a control. No differences in cytotoxicity
were observed when cells were exposed to ENP-containing paint particles, compared
with the same paint particles without ENPs. Paint particles containing ENPs did
not affect cell morphology, the release of reactive oxygen species or cytokines,
cell activity or cell death in a different manner to the same paint particles
without ENPs. The results suggest that paints doped with ENPs do not pose an
additional acute health hazard for humans.
PMID- 24358265
TI - Arbuscular mycorrhizal fungal networks vary throughout the growing season and
between successional stages.
AB - To date, few analyses of mutualistic networks have investigated successional or
seasonal dynamics. Combining interaction data from multiple time points likely
creates an inaccurate picture of the structure of networks (because these
networks are aggregated across time), which may negatively influence their
application in ecosystem assessments and conservation. Using a replicated
bipartite mutualistic network of arbuscular mycorrhizal (AM) fungal-plant
associations, detected using large sample numbers of plants and AM fungi
identified through molecular techniques, we test whether the properties of the
network are temporally dynamic either between different successional stages or
within the growing season. These questions have never been directly tested in the
AM fungal-plant mutualism or the vast majority of other mutualisms. We
demonstrate the following results: First, our examination of two different
successional stages (young and old forest) demonstrated that succession increases
the proportion of specialists within the community and decreases the number of
interactions. Second, AM fungal-plant mutualism structure changed throughout the
growing season as the number of links between partners increased. Third, we
observed shifts in associations between AM fungal and plant species throughout
the growing season, potentially reflecting changes in biotic and abiotic
conditions. Thus, this analysis opens up two entirely new areas of research: 1)
identifying what influences changes in plant-AM fungal associations in these
networks, and 2) what aspects of temporal variation and succession are of general
importance in structuring bipartite networks and plant-AM fungal communities.
PMID- 24358266
TI - Oscillatory underpinnings of mismatch negativity and their relationship with
cognitive function in patients with schizophrenia.
AB - BACKGROUND: Impairments in mismatch negativity (MMN) generation have been
consistently reported in patients with schizophrenia. However, underlying
oscillatory activity of MMN deficits in schizophrenia and the relationship with
cognitive impairments have not been investigated in detail. Time-frequency power
and phase analyses can provide more detailed measures of brain dynamics of MMN
deficits in schizophrenia. METHOD: 21 patients with schizophrenia and 21 healthy
controls were tested with a roving frequency paradigm to generate MMN. Time
frequency domain power and phase-locking (PL) analysis was performed on all
trials using short-time Fourier transforms with Hanning window tapering. A
comprehensive battery (CANTAB) was used to assess neurocognitive functioning.
RESULTS: Mean MMN amplitude was significantly lower in patients with
schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power
(95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170
and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple
domains of CANTAB. However, MMN impairments in amplitude and power were not
correlated with clinical measures, medication dose, social functioning or
neurocognitive performance. CONCLUSION: The findings from this study suggested
that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms
and associated impairments in gain control and perceptual changes, it may not be
a useful marker in association with clinical or cognitive changes. Trial-by-trial
EEG power analysis can be used as a measure of brain dynamics underlying MMN
deficits which also can have implications for the use of MMN as a biomarker for
drug discovery.
PMID- 24358267
TI - Hepatic SH2B1 and SH2B2 regulate liver lipid metabolism and VLDL secretion in
mice.
AB - SH2B1 is an SH2 and PH domain-containing adaptor protein. Genetic deletion of
SH2B1 results in obesity, type 2 diabetes, and fatty liver diseases in mice.
Mutations in SH2B1 are linked to obesity in humans. SH2B1 in the brain controls
energy balance and body weight at least in part by enhancing leptin sensitivity
in the hypothalamus. SH2B1 in peripheral tissues also regulates glucose and lipid
metabolism, presumably by enhancing insulin sensitivity in peripheral
metabolically-active tissues. However, the function of SH2B1 in individual
peripheral tissues is unknown. Here we generated and metabolically characterized
hepatocyte-specific SH2B1 knockout (HKO) mice. Blood glucose and plasma insulin
levels, glucose tolerance, and insulin tolerance were similar between HKO,
albumin-Cre, and SH2B1(f/f) mice fed either a normal chow diet or a high fat diet
(HFD). Adult-onset deletion of SH2B1 in the liver either alone or in combination
with whole body SH2B2 knockout also did not exacerbate HFD-induced insulin
resistance and glucose intolerance. Adult-onset, but not embryonic, deletion of
SH2B1 in the liver attenuated HFD-induced hepatic steatosis. In agreement, adult
onset deletion of hepatic SH2B1 decreased the expression of diacylglycerol
acyltransferase-2 (DGAT2) and increased the expression of adipose triglyceride
lipase (ATGL). Furthermore, deletion of liver SH2B1 in SH2B2 null mice attenuated
very low-density lipoprotein (VLDL) secretion. These data indicate that hepatic
SH2B1 is not required for the maintenance of normal insulin sensitivity and
glucose metabolism; however, it regulates liver triacylglycerol synthesis,
lipolysis, and VLDL secretion.
PMID- 24358268
TI - CD4 cell levels during treatment for tuberculosis (TB) in Ethiopian adults and
clinical markers associated with CD4 lymphocytopenia.
AB - BACKGROUND: The clinical correlations and significance of subnormal CD4 levels in
HIV-negative patients with TB are unclear. We have determined CD4 cell levels
longitudinally during anti-tuberculosis treatment (ATT) in patients, with and
without HIV co-infection, and their associations with clinical variables. METHOD:
Adults diagnosed with TB (maximum duration of ATT for 2 weeks, and with no
history of antiretroviral therapy (ART) in HIV-positive subjects) were included
consecutively in eight out-patient clinics in Ethiopia. Healthy individuals were
recruited for comparison at one of the study health centers. Data on patient
characteristics and physical findings were collected by trained nurses following
a structured questionnaire at inclusion and on follow-up visits at 2 and 6
months. In parallel, peripheral blood CD4 cell levels were determined. The
evolution of CD4 cell levels during ATT was assessed, and the association between
clinical characteristics and low CD4 cell levels at baseline was investigated
using regression analysis. RESULTS: In total, 1116 TB patients were included (307
HIV-infected). Among 809 HIV-negative patients, 200 (25%) had subnormal CD4 cell
counts (<500 cells/mm(3)), with <350 cells/mm(3) in 82 (10%) individuals. CD4
cell levels increased significantly during the course of ATT in both HIV+ and HIV
TB-patients, but did not reach the levels in healthy subjects (median 896
cells/mm(3)). Sputum smear status, signs of wasting (low mid upper arm
circumference (MUAC)), and bedridden state were significantly associated with low
CD4 cell counts. CONCLUSION: A high proportion of Ethiopian TB patients have
subnormal CD4 cell counts before starting treatment. Low CD4 cell levels are
associated with smear positive disease and signs of wasting. The continuous
increase of CD4 cell counts during the course of ATT suggest a reversible impact
of active TB on CD4 cell homeostasis, which may be considered in interpretation
of CD4 cell counts in HIV/TB co-infected subjects.
PMID- 24358269
TI - A replicating modified vaccinia tiantan strain expressing an avian-derived
influenza H5N1 hemagglutinin induce broadly neutralizing antibodies and cross
clade protective immunity in mice.
AB - To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is
necessary to develop a vaccine that would confer protection against homologous
and heterologous human H5N1 influenza viruses. Using a replicating modified
vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTTHA
QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain
A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005.
The immunogenicity profiles of both vaccine candidates were evaluated.
Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies
(Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades
1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination
inhibition (HI) antibodies inhibit the live autologous virus as well as a
homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004,
representing two human isolates from clade 2.2 and clade 1, respectively.
Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected
from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the
A/Viet Nam/1194/2004, respectively, but not control mice that received a mock
MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its
autologous strain. Our results suggest that it is feasible to use the H5 gene
from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when
using MVTT as a vector, to prevent infections against homologous and genetically
divergent human H5N1 influenza viruses.
PMID- 24358271
TI - A novel cell-sheet technology that achieves durable factor VIII delivery in a
mouse model of hemophilia A.
AB - Gene- or cell-based therapies aimed at creating delivery systems for coagulation
factor VIII (FVIII) protein have emerged as promising options for hemophilia A
treatment. However, several issues remain to be addressed regarding the
efficacies and adverse events of these new classes of therapies. To improve an
existing cell-based therapy involving the subcutaneous transplantation of FVIII
transduced blood outgrowth endothelial cells (BOECs), we employed a novel cell
sheet technology that allows individual dispersed cells to form a thin and
contiguous monolayer without traditional bioabsorbable scaffold matrices.
Compared to the traditional methodology, our cell-sheet approach resulted in
longer-term and 3-5-fold higher expression of FVIII (up to 11% of normal) in
recipient hemophilia A mice that lacked a FVIII humoral immune response due to
transient immunosuppression with cyclophosphamide. Histological studies revealed
that the transplanted BOEC sheets were structured as flat clusters, supporting
the long-term expression of therapeutic FVIII in plasma from an ectopic
subcutaneous space. Our novel tissue-engineering approach using genetically
modified BOEC sheets could aid in development of cell-based therapy that will
allow safe and effective in vivo delivery of functional FVIII protein in patients
with hemophilia A.
PMID- 24358270
TI - Increasing RpoS expression causes cell death in Borrelia burgdorferi.
AB - RpoS, one of the two alternative sigma factors in Borrelia burgdorferi, is
tightly controlled by multiple regulators and, in turn, determines expression of
many critical virulence factors. Here we show that increasing RpoS expression
causes cell death. The immediate effect of increasing RpoS expression was to
promote bacterial division and as a consequence result in a rapid increase in
cell number before causing bacterial death. No DNA fragmentation or degradation
was observed during this induced cell death. Cryo-electron microscopy showed
induced cells first formed blebs, which were eventually released from dying
cells. Apparently blebbing initiated cell disintegration leading to cell death.
These findings led us to hypothesize that increasing RpoS expression triggers
intracellular programs and/or pathways that cause spirochete death. The potential
biological significance of induced cell death may help B. burgdorferi regulate
its population to maintain its life cycle in nature.
PMID- 24358272
TI - Cerebral blood flow links insulin resistance and baroreflex sensitivity.
AB - Insulin resistance confers risk for diabetes mellitus and associates with a
reduced capacity of the arterial baroreflex to regulate blood pressure.
Importantly, several brain regions that comprise the central autonomic network,
which controls the baroreflex, are also sensitive to the neuromodulatory effects
of insulin. However, it is unknown whether peripheral insulin resistance relates
to activity within central autonomic network regions, which may in turn relate to
reduced baroreflex regulation. Accordingly, we tested whether resting cerebral
blood flow within central autonomic regions statistically mediated the
relationship between insulin resistance and an indirect indicator of baroreflex
regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling
adults free of confounding medical illnesses (48 men, 30-50 years old) who
completed protocols to assess fasting insulin and glucose levels, resting
baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity
was quantified by measuring the magnitude of spontaneous and sequential
associations between beat-by-beat systolic blood pressure and heart rate changes.
Individuals with greater insulin resistance, as measured by the homeostatic model
assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05).
Moreover, the relationship between insulin resistance and baroreflex sensitivity
was statistically mediated by cerebral blood flow in central autonomic regions,
including the insula and cingulate cortex (mediation coefficients < -0.06, p
values < .01). Activity within the central autonomic network may link insulin
resistance to reduced baroreflex sensitivity. Our observations may help to
characterize the neural pathways by which insulin resistance, and possibly
diabetes mellitus, relates to adverse cardiovascular outcomes.
PMID- 24358273
TI - Ethnic differences in glycaemic control in people with type 2 diabetes mellitus
living in Scotland.
AB - BACKGROUND AND AIMS: Previous studies have investigated the association between
ethnicity and processes of care and intermediate outcomes of diabetes, but there
are limited population-based studies available. The aim of this study was to use
population-based data to investigate the relationships between ethnicity and
glycaemic control in men and women with diabetes mellitus living in Scotland.
METHODS: We used a 2008 extract from the population-based national electronic
diabetes database of Scotland. The association between ethnicity with mean
glycaemic control in type 2 diabetes mellitus was examined in a retrospective
cohort study, including adjustment for a number of variables including age, sex,
socioeconomic status, body mass index (BMI), prescribed treatment and duration of
diabetes. RESULTS: Complete data for analyses were available for 56,333 White
Scottish adults, 2,535 Pakistanis, 857 Indians, 427 Chinese and 223 African
Caribbeans. All other ethnic groups had significantly (p<0.05) greater
proportions of people with suboptimal glycaemic control (HbA1c >58 mmol/mol,
7.5%) compared to the White Scottish group, despite generally younger mean age
and lower BMI. Fully adjusted odds ratios for suboptimal glycaemic control were
significantly higher among Pakistanis and Indians (1.85, 95% CI: 1.68-2.04, and
1.62,95% CI: 1.38-1.89) respectively. CONCLUSIONS: Pakistanis and Indians with
type 2 diabetes mellitus were more likely to have suboptimal glycaemic control
than the white Scottish population. Further research on health services and self
management are needed to understand the association between ethnicity and
glycaemic control to address ethnic disparities in glycaemic control.
PMID- 24358274
TI - Notch gamma-secretase inhibitor dibenzazepine attenuates angiotensin II-induced
abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms.
AB - Abdominal aortic aneurysm (AAA) is a life-threatening aortic disease in the
elderly. Activation of Notch1 pathway plays a critical role in the development of
AAA, but the underlying mechanisms remain poorly understood. In the present
study, we explored the mechanisms by which Notch1 activation regulates
angiotensin II (Ang II)-induced AAA formation and evaluated the therapeutic
potential of a new Notch gamma-secretase inhibitor, dibenzazepine (DBZ), for the
treatment of AAA. Apolipoprotein E knockout (Apo E(-/-)) mice infused for 4 weeks
with Ang II (1000 ng/kg/min, IP) using osmotic mini-pumps were received an
intraperitoneal injection of either vehicle or 1 mg/kg/d DBZ. Notch1 signaling
was activated in AAA tissue from both Ang II-infused Apo E(-/-) mice and human
undergoing AAA repair in vivo, with increased expression of Notch intracellular
domain (NICD) and its target gene Hes1, and this effect was effectively blocked
by DBZ. Moreover, infusion of Ang II markedly increased the incidence and
severity of AAA in Apo E(-/-) mice. In contrast, inhibition of Notch activation
by DBZ prevented AAA formation in vivo. Furthermore, DBZ markedly prevented Ang
II-stimulated accumulation of macrophages and CD4(+) T cells, and ERK-mediated
angiogenesis, simultaneously reversed Th2 response, in vivo. In conclusion, these
findings provide new insight into the multiple mechanisms of Notch signaling
involved in AAA formation and suggest that gamma-secretase inhibitor DBZ might be
a novel therapeutic drug for treating AAAS.
PMID- 24358275
TI - Role of endothelial progenitor cells and inflammatory cytokines in healing of
diabetic foot ulcers.
AB - BACKGROUND: To evaluate changes in endothelial progenitor cells (EPCs) and
cytokines in patients with diabetic foot ulceration (DFU) in association with
wound healing. METHODS: We studied healthy subjects, diabetic patients not at
risk of DFU, at risk of DFU and with active DFU. We prospectively followed the
DFU patients over a 12-week period. We also investigated similar changes in
diabetic rabbit and mouse models of wound healing. RESULTS: All EPC phenotypes
except the kinase insert domain receptor (KDR)(+)CD133(+) were reduced in the at
risk and the DFU groups compared to the controls. There were no major EPC
differences between the control and not at risk group, and between the at risk
and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor
(SCF) were increased in DFU patients. DFU patients who healed their ulcers had
lower CD34(+)KDR(+) count at visits 3 and 4, serum c-reactive protein (CRP) and
granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin
1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal
models when compared to their non-diabetic counterparts both before and ten days
after wounding. CONCLUSIONS: Uncomplicated diabetes does not affect EPCs. EPCs
are reduced in patients at risk or with DFU while complete wound healing is
associated with CD34(+)KDR(+) reduction, suggesting possible increased homing.
Low baseline CRP, IL-1alpha and GM-CSF serum levels were associated with complete
wound healing and may potentially serve as prognostic markers of DFU healing. No
animal model alone is representative of the human condition, indicating the need
for multiple experimental models.
PMID- 24358276
TI - Two residues in the basic region of the yeast transcription factor Yap8 are
crucial for its DNA-binding specificity.
AB - In Saccharomyces cerevisiae, the transcription factor Yap8 is a key determinant
in arsenic stress response. Contrary to Yap1, another basic region-leucine zipper
(bZIP) yeast regulator, Yap8 has a very restricted DNA-binding specificity and
only orchestrates the expression of ACR2 and ACR3 genes. In the DNA-binding basic
region, Yap8 has three distinct amino acids residues, Leu26, Ser29 and Asn31, at
sites of highly conserved positions in the other Yap family of transcriptional
regulators and Pap1 of Schizosaccharomyces pombe. To evaluate whether these
residues are relevant to Yap8 specificity, we first built a homology model of the
complex Yap8bZIP-DNA based on Pap1-DNA crystal structure. Several Yap8 mutants
were then generated in order to confirm the contribution of the residues
predicted to interact with DNA. Using bioinformatics analysis together with in
vivo and in vitro approaches, we have identified several conserved residues
critical for Yap8-DNA binding. Moreover, our data suggest that Leu26 is required
for Yap8 binding to DNA and that this residue together with Asn31, hinder Yap1
response element recognition by Yap8, thus narrowing its DNA-binding specificity.
Furthermore our results point to a role of these two amino acids in the stability
of the Yap8-DNA complex.
PMID- 24358277
TI - Pastoral practices to reverse shrub encroachment of sub-alpine grasslands: dung
beetles (coleoptera, scarabaeoidea) respond more quickly than vegetation.
AB - In recent decades, pastoral abandonment has produced profound ecological changes
in the Alps. In particular, the reduction in grazing has led to extensive shrub
encroachment of semi-natural grasslands, which may represent a threat to open
habitat biodiversity. To reverse shrub encroachment, we assessed short-term
effects of two different pastoral practices on vegetation and dung beetles
(Coleoptera, Scarabaeoidea). Strategic placement of mineral mix supplements (MMS)
and arrangement of temporary night camp areas (TNCA) for cattle were carried out
during summer 2011 in the Val Troncea Natural Park, north-western Italian Alps.
In 2012, one year after treatment, a reduction in shrub cover and an increase in
bare ground cover around MMS sites was detected. A more intense effect was
detected within TNCA through increases in forage pastoral value, and in the cover
and height of the herbaceous layer. Immediately after treatment, changes in dung
beetle diversity (total abundance, species richness, Shannon diversity, taxonomic
and functional diversity) showed a limited disturbance effect caused by high
cattle density. In contrast, dung beetle diversity significantly increased one
year later both at MMS and TNCA sites, with a stronger effect within TNCA.
Multivariate Regression Trees and associated Indicator Value analyses showed that
some ecologically relevant dung beetle species preferred areas deprived of shrub
vegetation. Our main conclusions are: i) TNCA are more effective than MMS in
terms of changes to vegetation and dung beetles, ii) dung beetles respond more
quickly than vegetation to pastoral practices, and iii) the main driver of the
rapid response by dung beetles is the removal of shrubs. The resulting increase
in dung beetle abundance and diversity, which are largely responsible for
grassland ecosystem functioning, may have a positive effect on meso-eutrophic
grassland restoration. Shrub encroachment in the Alps may therefore be reversed,
and restoration of grassland enhanced, by using appropriate pastoral practices.
PMID- 24358278
TI - SoftSearch: integration of multiple sequence features to identify breakpoints of
structural variations.
AB - BACKGROUND: Structural variation (SV) represents a significant, yet poorly
understood contribution to an individual's genetic makeup. Advanced next
generation sequencing technologies are widely used to discover such variations,
but there is no single detection tool that is considered a community standard. In
an attempt to fulfil this need, we developed an algorithm, SoftSearch, for
discovering structural variant breakpoints in Illumina paired-end next-generation
sequencing data. SoftSearch combines multiple strategies for detecting SV
including split-read, discordant read-pair, and unmated pairs. Co-localized split
reads and discordant read pairs are used to refine the breakpoints. RESULTS: We
developed and validated SoftSearch using real and synthetic datasets.
SoftSearch's key features are 1) not requiring secondary (or exhaustive primary)
alignment, 2) portability into established sequencing workflows, and 3) is
applicable to any DNA-sequencing experiment (e.g. whole genome, exome, custom
capture, etc.). SoftSearch identifies breakpoints from a small number of soft
clipped bases from split reads and a few discordant read-pairs which on their own
would not be sufficient to make an SV call. CONCLUSIONS: We show that SoftSearch
can identify more true SVs by combining multiple sequence features. SoftSearch
was able to call clinically relevant SVs in the BRCA2 gene not reported by other
tools while offering significantly improved overall performance.
PMID- 24358279
TI - Optical monitoring and detection of spinal cord ischemia.
AB - Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early
it may be amenable to treatment. Current methods use evoked potentials for
detection of spinal cord ischemia, a decades old technology whose warning signs
are indirect and significantly delayed from the onset of ischemia. Here we
introduce and demonstrate a prototype fiber optic device that directly measures
spinal cord blood flow and oxygenation. This technical advance in neurological
monitoring promises a new standard of care for detection of spinal cord ischemia
and the opportunity for early intervention. We demonstrate the probe in an adult
Dorset sheep model. Both open and percutaneous approaches were evaluated during
pharmacologic, physiological, and mechanical interventions designed to induce
variations in spinal cord blood flow and oxygenation. The induced variations were
rapidly and reproducibly detected, demonstrating direct measurement of spinal
cord ischemia in real-time. In the future, this form of hemodynamic spinal cord
diagnosis could significantly improve monitoring and management in a broad range
of patients, including those undergoing thoracic and abdominal aortic
revascularization, spine stabilization procedures for scoliosis and trauma,
spinal cord tumor resection, and those requiring management of spinal cord injury
in intensive care settings.
PMID- 24358280
TI - Gene expression-based dosimetry by dose and time in mice following acute
radiation exposure.
AB - Rapid and reliable methods for performing biological dosimetry are of paramount
importance in the event of a large-scale nuclear event. Traditional dosimetry
approaches lack the requisite rapid assessment capability, ease of use,
portability and low cost, which are factors needed for triaging a large number of
victims. Here we describe the results of experiments in which mice were acutely
exposed to (60)Co gamma rays at doses of 0 (control) to 10 Gy. Blood was obtained
from irradiated mice 0.5, 1, 2, 3, 5, and 7 days after exposure. mRNA expression
levels of 106 selected genes were obtained by reverse-transcription real time
PCR. Stepwise regression of dose received against individual gene transcript
expression levels provided optimal dosimetry at each time point. The results
indicate that only 4-7 different gene transcripts are needed to explain >= 0.69
of the variance (R(2)), and that receiver-operator characteristics, a measure of
sensitivity and specificity, of >= 0.93 for these statistical models were
achieved at each time point. These models provide an excellent description of the
relationship between the actual and predicted doses up to 6 Gy. At doses of 8 and
10 Gy there appears to be saturation of the radiation-response signals with a
corresponding diminution of accuracy. These results suggest that similar analyses
in humans may be advantageous for use in a field-portable device designed to
assess exposures in mass casualty situations.
PMID- 24358281
TI - Live birth from slow-frozen rabbit oocytes after in vivo fertilisation.
AB - In vivo fertilisation techniques such as intraoviductal oocyte transfer have been
considered as alternatives to bypass the inadequacy of conventional in vitro
fertilisation in rabbit. There is only one study in the literature, published in
1989, that reports live offspring from cryopreserved rabbit oocytes. The aim of
the present study was to establish the in vivo fertilisation procedure to
generate live offspring with frozen oocytes. First, the effect of two recipient
models (i) ovariectomised or (ii) oviduct ligated immediately after transfer on
the ability of fresh oocytes to fertilise were compared. Second, generation of
live offspring from slow-frozen oocytes was carried out using the ligated oviduct
recipient model. Throughout the experiment, recipients were artificially
inseminated 9 hours prior to oocyte transfer. In the first experiment, two days
after unilateral transfer of fresh oocytes, oviducts and uterine horns were
flushed to assess embryo recovery rates. The embryo recovery rates were low
compared to control in both ovariectomised and ligated oviduct groups. However,
ligated oviduct recipient showed significantly (P<0.05) higher embryo recovery
rates compared to ovariectomised and control-transferred. In the second
experiment, using bilateral oviduct ligation model, all females that received
slow-frozen oocytes became pregnant and delivered a total of 4 live young
naturally. Thus, in vivo fertilisation is an effective technique to generate live
offspring using slow-frozen oocytes in rabbits.
PMID- 24358282
TI - Rating of Everyday Arm-Use in the Community and Home (REACH) scale for capturing
affected arm-use after stroke: development, reliability, and validity.
AB - OBJECTIVE: To develop a brief, valid and reliable tool [the Rating of Everyday
Arm-use in the Community and Home (REACH) scale] to classify affected upper limb
use after stroke outside the clinical setting. METHODS: Focus groups with
clinicians, patients and caregivers (n = 33) and a literature review were
employed to develop the REACH scale. A sample of community-dwelling individuals
with stroke was used to assess the validity (n = 96) and inter-rater reliability
(n = 73) of the new scale. RESULTS: The REACH consists of separate scales for
dominant and non-dominant affected upper limbs, and takes five minutes to
administer. Each scale consists of six categories that capture 'no use' to 'full
use'. The intraclass correlation coefficient and weighted kappa for inter-rater
reliability were 0.97 (95% confidence interval: 0.95-0.98) and 0.91 (0.89-0.93)
respectively. REACH scores correlated with external measures of upper extremity
use, function and impairment (rho = 0.64-0.94). CONCLUSIONS: The REACH scale is a
reliable, quick-to-administer tool that has strong relationships to other
measures of upper limb use, function and impairment. By providing a rich
description of how the affected upper limb is used outside of the clinical
setting, the REACH scale fills an important gap among current measures of upper
limb use and is useful for understanding the long term effects of stroke
rehabilitation.
PMID- 24358283
TI - Analysis of high affinity self-association by fluorescence optical sedimentation
velocity analytical ultracentrifugation of labeled proteins: opportunities and
limitations.
AB - Sedimentation velocity analytical ultracentrifugation (SV) is a powerful first
principle technique for the study of protein interactions, and allows a rigorous
characterization of binding stoichiometry and affinities. A recently introduced
commercial fluorescence optical detection system (FDS) permits analysis of high
affinity interactions by SV. However, for most proteins the attachment of an
extrinsic fluorophore is an essential prerequisite for analysis by FDS-SV. Using
the glutamate receptor GluA2 amino terminal domain as a model system for high
affinity homo-dimerization, we demonstrate how the experimental design and choice
of fluorescent label can impact both the observed binding constants as well as
the derived hydrodynamic parameter estimates for the monomer and dimer species.
Specifically, FAM (5,6-carboxyfluorescein) was found to create different
populations of artificially high-affinity and low-affinity dimers, as indicated
by both FDS-SV and the kinetics of dimer dissociation studied using a bench-top
fluorescence spectrometer and Forster Resonance Energy Transfer. By contrast,
Dylight488 labeled GluA2, as well as GluA2 expressed as an EGFP fusion protein,
yielded results consistent with estimates for unlabeled GluA2. Our study suggests
considerations for the choice of labeling strategies, and highlights experimental
designs that exploit specific opportunities of FDS-SV for improving the
reliability of the binding isotherm analysis of interacting systems.
PMID- 24358284
TI - The numbers tell it all: students don't like numbers!
AB - Undergraduate Students' interest in taking quantitative vs. non quantitative
courses has received limited attention even though it has important consequences
for higher education. Previous studies have collected course interest ratings at
the end of the courses as part of student evaluation of teaching (SET) ratings,
which may confound prior interest in taking these courses with students' actual
experience in taking them. This study is the first to examine undergraduate
students' interest in quantitative vs. non quantitative courses in their first
year of studies before they have taken any quantitative courses. Three hundred
and forty students were presented with descriptions of 44 psychology courses and
asked to rate their interest in taking each course. Student interest in taking
quantitative vs non quantitative courses was very low; the mean interest in
statistics courses was nearly 6 SDs below the mean interest in non quantitative
courses. Moreover, women were less interested in taking quantitative courses than
men. Our findings have several far-reaching implications. First, evaluating
professors teaching quantitative vs. non quantitative courses against the same
SET standard may be inappropriate. Second, if the same SET standard is used for
the evaluation of faculty teaching quantitative vs. non quantitative courses,
faculty are likely to teach to SETs rather than focus on student learning. Third,
universities interested primarily in student satisfaction may want to expunge
quantitative courses from their curricula. In contrast, universities interested
in student learning may want to abandon SETs as a primary measure of faculty
teaching effectiveness. Fourth, undergraduate students who are not interested in
taking quantitative courses are unlikely to pursue graduate studies in
quantitative psychology and unlikely to be able to competently analyze data
independently.
PMID- 24358285
TI - Recovery of renal function among ESRD patients in the US medicare program.
AB - BACKGROUND: Patients started on long term hemodialysis have typically had low
rates of reported renal recovery with recent estimates ranging from 0.9-2.4%
while higher rates of recovery have been reported in cohorts with higher
percentages of patients with acute renal failure requiring dialysis. STUDY
DESIGN: Our analysis followed approximately 194,000 patients who were initiated
on hemodialysis during a 2-year period (2008 & 2009) with CMS-2728 forms
submitted to CMS by dialysis facilities, cross-referenced with patient record
updates through the end of 2010, and tracked through December 2010 in the CMS
SIMS registry. RESULTS: We report a sustained renal recovery (i.e no return to
ESRD during the available follow up period) rate among Medicare ESRD patients of
> 5% - much higher than previously reported. Recovery occurred primarily in the
first 2 months post incident dialysis, and was more likely in cases with renal
failure secondary to etiologies associated with acute kidney injury. Patients
experiencing sustained recovery were markedly less likely than true long-term
ESRD patients to have permanent vascular accesses in place at incident
hemodialysis, while non-White patients, and patients with any prior nephrology
care appeared to have significantly lower rates of renal recovery. We also found
widespread geographic variation in the rates of renal recovery across the United
States. CONCLUSIONS: Renal recovery rates in the US Medicare ESRD program are
higher than previously reported and appear to have significant geographic
variation. Patients with diagnoses associated with acute kidney injury who are
initiated on long-term hemodialysis have significantly higher rates of renal
recovery than the general ESRD population and lower rates of permanent access
placement.
PMID- 24358286
TI - Thermal/optical methods for elemental carbon quantification in soils and urban
dusts: equivalence of different analysis protocols.
AB - Quantifying elemental carbon (EC) content in geological samples is challenging
due to interferences of crustal, salt, and organic material. Thermal/optical
analysis, combined with acid pretreatment, represents a feasible approach.
However, the consistency of various thermal/optical analysis protocols for this
type of samples has never been examined. In this study, urban street dust and
soil samples from Baoji, China were pretreated with acids and analyzed with four
thermal/optical protocols to investigate how analytical conditions and optical
correction affect EC measurement. The EC values measured with reflectance
correction (ECR) were found always higher and less sensitive to temperature
program than the EC values measured with transmittance correction (ECT). A high
temperature method with extended heating times (STN120) showed the highest
ECT/ECR ratio (0.86) while a low-temperature protocol (IMPROVE-550), with heating
time adjusted for sample loading, showed the lowest (0.53). STN ECT was higher
than IMPROVE ECT, in contrast to results from aerosol samples. A higher peak
inert-mode temperature and extended heating times can elevate ECT/ECR ratios for
pretreated geological samples by promoting pyrolyzed organic carbon (PyOC)
removal over EC under trace levels of oxygen. Considering that PyOC within filter
increases ECR while decreases ECT from the actual EC levels, simultaneous ECR and
ECT measurements would constrain the range of EC loading and provide information
on method performance. Further testing with standard reference materials of
common environmental matrices supports the findings. Char and soot fractions of
EC can be further separated using the IMPROVE protocol. The char/soot ratio was
lower in street dusts (2.2 on average) than in soils (5.2 on average), most
likely reflecting motor vehicle emissions. The soot concentrations agreed with EC
from CTO-375, a pure thermal method.
PMID- 24358287
TI - Sensitivity and specificity of hypnosis effects on gastric myoelectrical
activity.
AB - OBJECTIVES: The effects of hypnosis on physiological (gastrointestinal) functions
are incompletely understood, and it is unknown whether they are hypnosis-specific
and gut-specific, or simply unspecific effects of relaxation. DESIGN: Sixty-two
healthy female volunteers were randomly assigned to either a single session of
hypnotic suggestion of ingesting an appetizing meal and an unappetizing meal, or
to relax and concentrate on having an appetizing or unappetizing meal, while the
electrogastrogram (EGG) was recorded. At the end of the session, participants
drank water until they felt full, in order to detect EGG-signal changes after
ingestion of a true gastric load. During both conditions participants reported
their subjective well-being, hunger and disgust at several time points. RESULTS:
Imagining eating food induced subjective feelings of hunger and disgust as well
as changes in the EGG similar to, but more pronounced than those seen with a real
gastric water load during both hypnosis and relaxation conditions. These effects
were more pronounced when imagining an appetizing meal than with an unappetizing
meal. There was no significant difference between the hypnosis and relaxation
conditions. CONCLUSION: Imagination with and without hypnosis exhibits similar
changes in subjective and objective measures in response to imagining an
appetizing and an unappetizing food, indicating high sensitivity but low
specificity.
PMID- 24358289
TI - Evolutionary pattern of the FAE1 gene in brassicaceae and its correlation with
the erucic acid trait.
AB - The fatty acid elongase 1 (FAE1) gene catalyzes the initial condensation step in
the elongation pathway of VLCFA (very long chain fatty acid) biosynthesis and is
thus a key gene in erucic acid biosynthesis. Based on a worldwide collection of
62 accessions representing 14 tribes, 31 genera, 51 species, 4 subspecies and 7
varieties, we conducted a phylogenetic reconstruction and correlation analysis
between genetic variations in the FAE1 gene and the erucic acid trait, attempting
to gain insight into the evolutionary patterns and the correlations between
genetic variations in FAE1 and trait variations. The five clear, deeply diverged
clades detected in the phylogenetic reconstruction are largely congruent with a
previous multiple gene-derived phylogeny. The Ka/Ks ratio (<1) and overall low
level of nucleotide diversity in the FAE1 gene suggest that purifying selection
is the major evolutionary force acting on this gene. Sequence variations in FAE1
show a strong correlation with the content of erucic acid in seeds, suggesting a
causal link between the two. Furthermore, we detected 16 mutations that were
fixed between the low and high phenotypes of the FAE1 gene, which constitute
candidate active sites in this gene for altering the content of erucic acid in
seeds. Our findings begin to shed light on the evolutionary pattern of this
important gene and represent the first step in elucidating how the sequence
variations impact the production of erucic acid in plants.
PMID- 24358288
TI - Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling
following myocardial infarction: involvement in fibrosis and apoptosis.
AB - Ataxia telangiectasia mutated kinase (ATM) is a cell cycle checkpoint protein
activated in response to DNA damage. We recently reported that ATM plays a
protective role in myocardial remodeling following beta-adrenergic receptor
stimulation. Here we investigated the role of ATM in cardiac remodeling using
myocardial infarction (MI) as a model. METHODS AND RESULTS: Left ventricular (LV)
structure, function, apoptosis, fibrosis, and protein levels of apoptosis- and
fibrosis-related proteins were examined in wild-type (WT) and ATM heterozygous
knockout (hKO) mice 7 days post-MI. Infarct sizes were similar in both MI groups.
However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode
echocardiography revealed decreased percent fractional shortening (%FS) and
ejection fraction (EF) in both MI groups when compared to their respective sham
groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs
hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI.
Fibrosis, apoptosis, and alpha-smooth muscle actin staining was significantly
higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a
similar extent in the infarct regions of both groups. MMP-9 protein levels were
increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and
activity were significantly lower in the infarct region of WT vs hKO. TIMP-2
protein levels similarly increased in both MI groups, whereas TIMP-4 protein
levels were significantly lower in the infarct region of hKO group.
Phosphorylation of p53 protein was higher, while protein levels of manganese
superoxide dismutase were significantly lower in the infarct region of hKO vs WT.
In vitro, inhibition of ATM using KU-55933 increased oxidative stress and
apoptosis in cardiac myocytes.
PMID- 24358290
TI - Clozapine prescribing in a Canadian outpatient population.
AB - OBJECTIVE: Description of demographics of an outpatient population of clozapine
users. METHODS: Retrospective chart review study of an urban population diagnosed
with schizophrenia. Assessment of therapeutic histories in relation to clinical
practice guidelines. RESULTS: Seventy-seven of the 467 patients were on clozapine
therapy. Average patients' age was 39.4 +/- 11.8 years) and 68% were males. The
majority of patients (68%) had tried 3 or more antipsychotics before switching to
clozapine, 21% had tried two and 11% had tried one. Median length of therapy
prior to clozapine initiation was 8.9 years in males and 7.7 years in females.
CONCLUSION: Until 2010, the use of clozapine was often delayed and more than 2
antipsychotic medications were tried for relatively long periods of time before
patients were switched to this effective agent.
PMID- 24358291
TI - Overweight people have low levels of implicit weight bias, but overweight nations
have high levels of implicit weight bias.
AB - Although a greater degree of personal obesity is associated with weaker
negativity toward overweight people on both explicit (i.e., self-report) and
implicit (i.e., indirect behavioral) measures, overweight people still prefer
thin people on average. We investigated whether the national and cultural context
- particularly the national prevalence of obesity - predicts attitudes toward
overweight people independent of personal identity and weight status. Data were
collected from a total sample of 338,121 citizens from 71 nations in 22 different
languages on the Project Implicit website (https://implicit.harvard.edu/) between
May 2006 and October 2010. We investigated the relationship of the explicit and
implicit weight bias with the obesity both at the individual (i.e., across
individuals) and national (i.e., across nations) level. Explicit weight bias was
assessed with self-reported preference between overweight and thin people;
implicit weight bias was measured with the Implicit Association Test (IAT). The
national estimates of explicit and implicit weight bias were obtained by
averaging the individual scores for each nation. Obesity at the individual level
was defined as Body Mass Index (BMI) scores, whereas obesity at the national
level was defined as three national weight indicators (national BMI, national
percentage of overweight and underweight people) obtained from publicly available
databases. Across individuals, greater degree of obesity was associated with
weaker implicit negativity toward overweight people compared to thin people.
Across nations, in contrast, a greater degree of national obesity was associated
with stronger implicit negativity toward overweight people compared to thin
people. This result indicates a different relationship between obesity and
implicit weight bias at the individual and national levels.
PMID- 24358292
TI - YopP-expressing variant of Y. pestis activates a potent innate immune response
affording cross-protection against yersiniosis and tularemia [corrected].
AB - Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease
with a high mortality rate if not quickly treated. The existence of antibiotic
resistant Y. pestis strains emphasizes the need for the development of novel
countermeasures against plague. We previously reported the generation of a
recombinant Y. pestis strain (Kim53DeltaJ+P) that over-expresses Y.
enterocolitica YopP. When this strain was administered subcutaneously to mice, it
elicited a fast and effective protective immune response in models of bubonic,
pneumonic and septicemic plague. In the present study, we further characterized
the immune response induced by the Kim53DeltaJ+P recombinant strain. Using a
panel of mouse strains defective in specific immune functions, we observed the
induction of a prompt protective innate immune response that was interferon-gamma
dependent. Moreover, inoculation of mice with Y. pestis Kim53DeltaJ+P elicited a
rapid protective response against secondary infection by other bacterial
pathogens, including the enteropathogen Y. enterocolitica and the respiratory
pathogen Francisella tularensis. Thus, the development of new therapies to
enhance the innate immune response may provide an initial critical delay in
disease progression following the exposure to highly virulent bacterial
pathogens, extending the time window for successful treatment.
PMID- 24358293
TI - The Fis protein has a stimulating role in initiation of replication in
Escherichia coli in vivo.
AB - The Fis protein is a nucleoid associated protein that has previously been
reported to act negatively in initiation of replication in Escherichia coli. In
this work we have examined the influence of this protein on the initiation of
replication under different growth conditions using flow cytometry. The Fis
protein was found to be increasingly important with increasing growth rate.
During multi-fork replication severe under-initiation occurred in cells lacking
the Fis protein; the cells initiated at an elevated mass, had fewer origins per
cell and the origins were not initiated in synchrony. These results suggest a
positive role for the Fis protein in the initiation of replication.
PMID- 24358294
TI - Matrix metalloproteinase-3 in odontoblastic cells derived from ips cells: unique
proliferation response as odontoblastic cells derived from ES cells.
AB - We previously reported that matrix metalloproteinase (MMP)-3 accelerates wound
healing following dental pulp injury. In addition, we reported that a
proinflammatory cytokine mixture (tumor necrosis factor-alpha, interleukin (IL)
1beta and interferon-gamma) induced MMP-3 activity in odontoblast-like cells
derived from mouse embryonic stem (ES) cells, suggesting that MMP-3 plays a
potential unique physiological role in wound healing and regeneration of dental
pulp in odontoblast-like cells. In this study, we tested the hypothesis that
upregulation of MMP-3 activity by IL-1beta promotes proliferation and apoptosis
of purified odontoblast-like cells derived from induced pluripotent stem (iPS)
and ES cells. Each odontoblast-like cell was isolated and incubated with
different concentrations of IL-1beta. MMP-3 mRNA and protein expression were
assessed using RT-PCR and western blotting, respectively. MMP-3 activity was
measured using immunoprecipitation and a fluorescence substrate. Cell
proliferation and apoptosis were determined using ELISA for BrdU and DNA
fragmentation, respectively. siRNA was used to reduce MMP-3 transcripts in these
cells. Treatment with IL-1beta increased MMP-3 mRNA and protein levels, and MMP-3
activity in odontoblast-like cells. Cell proliferation was found to markedly
increase with no changes in apoptosis. Endogenous tissue inhibitor of
metalloproteinase (TIMP)-1 and TIMP-2 were constitutively expressed during all
experiments. The exocytosis inhibitor, Exo1, potently suppressed the appearance
of MMP-3 in the conditioned medium. Treatment with siRNA against MMP-3 suppressed
an IL-1beta-induced increase in MMP-3 expression and activity, and also
suppressed cell proliferation, but unexpectedly increased apoptosis in these
cells (P<0.05). Exogenous MMP-3 was found to induce cell proliferation in
odontoblast-like cells derived from iPS cells and ES cells. This siRNA-mediated
increase in apoptosis could be reversed with exogenous MMP-3 stimulation
(P<0.05). Taken together, IL-1beta induced MMP-3-regulated cell proliferation and
suppressed apoptosis in odontoblast-like cells derived from iPS and ES cells.
PMID- 24358295
TI - Quantitative analysis of porcine reproductive and respiratory syndrome (PRRS)
viremia profiles from experimental infection: a statistical modelling approach.
AB - Porcine reproductive and respiratory syndrome (PRRS) is one of the most
economically significant viral diseases facing the global swine industry. Viremia
profiles of PRRS virus challenged pigs reflect the severity and progression of
infection within the host and provide crucial information for subsequent control
measures. In this study we analyse the largest longitudinal PRRS viremia dataset
from an in-vivo experiment. The primary objective was to provide a suitable
mathematical description of all viremia profiles with biologically meaningful
parameters for quantitative analysis of profile characteristics. The Wood's
function, a gamma-type function, and a biphasic extended Wood's function were fit
to the individual profiles using Bayesian inference with a likelihood framework.
Using maximum likelihood inference and numerous fit criteria, we established that
the broad spectrum of viremia trends could be adequately represented by either
uni- or biphasic Wood's functions. Three viremic categories emerged: cleared (uni
modal and below detection within 42 days post infection(dpi)), persistent
(transient experimental persistence over 42 dpi) and rebound (biphasic within 42
dpi). The convenient biological interpretation of the model parameters estimates,
allowed us not only to quantify inter-host variation, but also to establish
common viremia curve characteristics and their predictability. Statistical
analysis of the profile characteristics revealed that persistent profiles were
distinguishable already within the first 21 dpi, whereas it is not possible to
predict the onset of viremia rebound. Analysis of the neutralizing antibody(nAb)
data indicated that there was a ubiquitous strong response to the homologous
PRRSV challenge, but high variability in the range of cross-protection of the
nAbs. Persistent pigs were found to have a significantly higher nAb cross
protectivity than pigs that either cleared viremia or experienced rebound within
42 dpi. Our study provides novel insights into the nature and degree of variation
of hosts' responses to infection as well as new informative traits for subsequent
genomic and modelling studies.
PMID- 24358296
TI - Symptoms in response to controlled diesel exhaust more closely reflect exposure
perception than true exposure.
AB - BACKGROUND: Diesel exhaust (DE) exposures are very common, yet exposure-related
symptoms haven't been rigorously examined. OBJECTIVE: Describe symptomatic
responses to freshly generated and diluted DE and filtered air (FA) in a
controlled human exposure setting; assess whether such responses are altered by
perception of exposure. METHODS: 43 subjects participated within three double
blind crossover experiments to order-randomized DE exposure levels (FA and DE
calibrated at 100 and/or 200 micrograms/m(3) particulate matter of diameter less
than 2.5 microns), and completed questionnaires regarding symptoms and dose
perception. RESULTS: For a given symptom cluster, the majority of those exposed
to moderate concentrations of diesel exhaust do not report such symptoms. The
most commonly reported symptom cluster was of the nose (29%). Blinding to
exposure is generally effective. Perceived exposure, rather than true exposure,
is the dominant modifier of symptom reporting. CONCLUSION: Controlled human
exposure to moderate-dose diesel exhaust is associated with a range of mild
symptoms, though the majority of individuals will not experience any given
symptom. Blinding to DE exposure is generally effective. Perceived DE exposure,
rather than true DE exposure, is the dominant modifier of symptom reporting.
PMID- 24358297
TI - The sodium/proline transporter PutP of Helicobacter pylori.
AB - Helicobacter pylori is cause of chronic gastritis, duodenal ulcer and gastric
carcinoma in humans. L-proline is a preferred energy source of the
microaerophilic bacterium. Previous analyses revealed that HpputP and HpputA, the
genes that are predicted to play a central role in proline metabolism as they
encode for the proline transporter and proline dehydrogenase, respectively, are
essential for stomach colonization. Here, the molecular basis of proline
transport in H. pylori by HpPutP was investigated experimentally for the first
time. Measuring radiolabeled substrate transport in H. pylori and E. coli
heterologously expressing HpputP as well as in proteoliposomes reconstituted with
HpPutP, we demonstrate that the observed proline transport in H. pylori is
mediated by HpPutP. HpPutP is specific and exhibits a high affinity for L
proline. Notably, L-proline transport is exclusively dependent on Na(+) as
coupling ion, i.e., Na(+)/L-proline symport, reminiscent to the properties of
PutP of E. coli even though H. pylori lives in a more acidic environment.
Homology model-based structural comparisons and substitution analyses identified
amino acids crucial for function. HpPutP-catalyzed proline uptake was efficiently
inhibited by the known proline analogs 3,4-dehydro-D,L-proline and L-azetidine-2
carboxylic acid.
PMID- 24358298
TI - Tat peptide-mediated soluble expression of the membrane protein LSECtin-CRD in
Escherichia coli.
AB - The human liver and lymph node sinusoidal endothelial cell C-type lectin
(hLSECtin), a type II integral membrane protein, containing a Ca(2+)-dependent
carbohydrate recognition domain (CRD), has a well-established biological
activity, yet its three-dimensional structure is unknown due to low expression
yields and aggregation into inclusion bodies. Previous study has demonstrated
that the HIV-1 virus-encoded Tat peptide ('YGRKKRRQRRR') can increase the yields
and the solubility of heterologous proteins. However, whether the Tat peptide
could promote the high-yield and soluble expression of membrane proteins in
Escherichia coli is not known. Therefore, the prokaryotic expression vector
pET28b-Tat-hLSECtin-CRD (using pET28b and pET28b-hLSECtin-CRD as controls) was
constructed, and transformed into E. coli BL21 (DE3) cells and induced with
isopropyl-beta-d-thiogalactoside (IPTG) followed with identifying by SDS-PAGE and
Western blot. Subsequently, the bacterial subcellular structure, in which
overexpressed the heterologous proteins Tat-hLSECtin-CRD and Tat-free hLSECtin
CRD, was analyzed by transmission electron microscope (TEM) respectively, and the
mannose-binding activity of Tat-hLSECtin-CRD was also determined. Expectedly, the
solubility of Tat-LSECtin-CRD significantly increased compared to Tat-free
LSECtin-CRD (**p < 0.01) with prolonged time, and the Tat-LSECtin-CRD had a
significant mannose-binding activity. The subcellular structure analysis
indicated that the bacterial cells overexpressed Tat-hLSECtin-CRD exhibited
denser region compared with controls, while dot denser region aggregated in the
two ends of bacterial cells overexpressed Tat-free hLSECtin-CRD. This study
provided a novel method for improving the soluble expression of membrane proteins
in prokaryotic systems by fusion with the Tat peptide, which may be potentially
expanded to the expression of other membrane proteins.
PMID- 24358299
TI - Efficicent (R)-phenylethanol production with enantioselectivity-alerted (S)
carbonyl reductase II and NADPH regeneration.
AB - The NADPH-dependent (S)-carbonyl reductaseII from Candida parapsilosis catalyzes
acetophenone to chiral phenylethanol in a very low yield of 3.2%. Site-directed
mutagenesis was used to design two mutants Ala220Asp and Glu228Ser, inside or
adjacent to the substrate-binding pocket. Both mutations caused a significant
enantioselectivity shift toward (R)-phenylethanol in the reduction of
acetophenone. The variant E228S produced (R)-phenylethanol with an optical purity
above 99%, in 80.2% yield. The E228S mutation resulted in a 4.6-fold decrease in
the K M value, but nearly 5-fold and 21-fold increases in the k cat and k cat/K M
values with respect to the wild type. For NADPH regeneration, Bacillus sp. YX-1
glucose dehydrogenase was introduced into the (R)-phenylethanol pathway. A
coexpression system containing E228S and glucose dehydrogenase was constructed.
The system was optimized by altering the coding gene order on the plasmid and
using the Shine-Dalgarno sequence and the aligned spacing sequence as a linker
between them. The presence of glucose dehydrogenase increased the NADPH
concentration slightly and decreased NADP(+) pool 2- to 4-fold; the NADPH/NADP(+)
ratio was improved 2- to 5-fold. The recombinant Escherichia coli/pET-MS-SD-AS-G,
with E228S located upstream and glucose dehydrogenase downstream, showed
excellent performance, giving (R)-phenylethanol of an optical purity of 99.5 % in
92.2% yield in 12 h in the absence of an external cofactor. When 0.06 mM NADP(+)
was added at the beginning of the reaction, the reaction duration was reduced to
1 h. Optimization of the coexpression system stimulated an over 30-fold increase
in the yield of (R)-phenylethanol, and simultaneously reduced the reaction time
48-fold compared with the wild-type enzyme. This report describes possible
mechanisms for alteration of the enantiopreferences of carbonyl reductases by
site mutation, and cofactor rebalancing pathways for efficient chiral alcohols
production.
PMID- 24358300
TI - Creating rat model for hypoxic brain damage in neonates by oxygen deprivation.
AB - Current study explores the feasibility of using a non-surgical method of oxygen
deprivation to create Hypoxic brain damage in neonatal rats for medical studies.
7-day-old Sprague Dowley (SD) rats were kept in a container with low oxygen level
(8%) for 1.5h. A second group had bilateral cephalic artery ligation before the
1.5h-low oxygen treatment, a method similar to the popular Rice method, to expose
the brain to both hypoxic and ischemic situations. Short term neural functions
and brain water weights were evaluated 1 day after the hypoxic treatment. Brain
pathology and histology were also examined at 1 day and 3 days after the hypoxic
treatment. Both groups showed impaired neural functions and increased brain water
weight compared to the controls. Histology studies also revealed injuries in the
subcortex, hippocampus and lateral ventricle in the brains from both groups.
There is no significant difference in the degree of brain damages observed in the
two groups. Our work demonstrated that oxygen deprivation alone is sufficient to
cause brain damages similar to those seen in Hypoxic-ischemic brain disease
(HIBD). Because this method avoids the invasive surgical procedure and therefore
reduces the stress and mortality of laboratory animals during the experiment, we
recommend it to be the favorable method for creating rat models for HIBD studies.
PMID- 24358301
TI - Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human
osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced
apoptosis.
AB - Anticancer effects of dendropanoxide (DP) newly isolated from leaves and stem of
Dendropanax morbifera Leveille were firstly investigated in this study. DP
inhibited cell proliferation and induced apoptosis in dose- and time-dependent
manner in MG-63 human osteosarcoma cells, which was dependent on the release of
cytochrome c to the cytosol and the activation of caspases. Moreover, the DP
treated cells exhibited autophagy, as characterized by the punctuate patterns of
microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and
the appearance of autophagic vacuoles by MDC staining. The expression levels of
ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of
autophagy by 3-methyladenine (3-MA) and wortmannin (Wort) significantly enhanced
DP-induced apoptosis. DP treatment also caused a time-dependent increase in
protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and
inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP
induced autophagy that was accompanied by an increased apoptosis and a decreased
cell viability. These results indicate a cytoprotective function of autophagy
against DP-induced apoptosis and suggest that the combination of DP treatment
with autophagy inhibition may be a promising strategy for human osteosarcoma
control. Taken together, this study demonstrated for the first time that DP could
induce autophagy through ERK1/2 activation in human osteosarcoma cells and
autophagy inhibition enhanced DP-induced apoptosis.
PMID- 24358302
TI - Structure and function of a novel cellulase 5 from sugarcane soil metagenome.
AB - Cellulases play a key role in enzymatic routes for degradation of plant cell-wall
polysaccharides into simple and economically-relevant sugars. However, their low
performance on complex substrates and reduced stability under industrial
conditions remain the main obstacle for the large-scale production of cellulose
derived products and biofuels. Thus, in this study a novel cellulase with unusual
catalytic properties from sugarcane soil metagenome (CelE1) was isolated and
characterized. The polypeptide deduced from the celE1 gene encodes a unique
glycoside hydrolase domain belonging to GH5 family. The recombinant enzyme was
active on both carboxymethyl cellulose and beta-glucan with an endo-acting mode
according to capillary electrophoretic analysis of cleavage products. CelE1
showed optimum hydrolytic activity at pH 7.0 and 50 degrees C with remarkable
activity at alkaline conditions that is attractive for industrial applications in
which conventional acidic cellulases are not suitable. Moreover, its three
dimensional structure was determined at 1.8 A resolution that allowed the
identification of an insertion of eight residues in the beta8-alpha8 loop of the
catalytic domain of CelE1, which is not conserved in its psychrophilic orthologs.
This 8-residue-long segment is a prominent and distinguishing feature of
thermotolerant cellulases 5 suggesting that it might be involved with thermal
stability. Based on its unconventional characteristics, CelE1 could be
potentially employed in biotechnological processes that require thermotolerant
and alkaline cellulases.
PMID- 24358303
TI - Inhibition of store-operated calcium entry attenuates MPP(+)-induced oxidative
stress via preservation of mitochondrial function in PC12 cells: involvement of
Homer1a.
AB - The process of store-operated calcium entry (SOCE), whereby the release of
intracellular Ca(2+) from endoplasmic reticulum (ER) activates Ca(2+) influx
channels in the plasma membrane, has been demonstrated to impact a diverse range
of cell functions. In the present study, we investigated the potential protective
effect of SOCE inhibition against 1-methyl-4-phenylpyridinium (MPP(+)) injury by
using pharmacological antagonists or specific small interfering RNA (siRNA) in
PC12 cells. The results showed that both antagonists (15 MUM MRS-1845 and 50 MUM
ML-9) and stromal interacting molecule-1 (STIM1) targeted siRNA (Si-STIM1)
significantly increased cell viability, decreased apoptotic cell death and
reduced intracellular reactive oxygen species (ROS) production and lipid
peroxidation in MPP(+) injured PC12 cells. SOCE inhibition also prevented MPP(+)
induced mitochondrial dysfunction and activation of mitochondrial related
apoptotic factors, while had no effect on mitochondrial biogenesis. Moreover,
inhibition of SOCE by antagonists and siRNA increased the expression levels of
Homer1a mRNA and protein, and knockdown of Homer1a expression by specific siRNA
partly reversed the protective effects induced by SOCE inhibition in PC12 cells.
All these results indicated that SOCE inhibition protected PC12 cells against
MPP(+) insult through upregulation of Homer1a expression, and SOCE might be an
ideal target for investigating therapeutic strategy against neuronal injury in PD
patients.
PMID- 24358304
TI - Niche-dependent gene expression profile of intratumoral heterogeneous ovarian
cancer stem cell populations.
AB - Intratumoral heterogeneity challenges existing paradigms for anti-cancer therapy.
We have previously demonstrated that the human embryonic stem cells (hESC)
derived cellular microenvironment in immunocompromised mice, enables functional
distinction of heterogeneous tumor cells, including cells which do not grow into
a tumor in a conventional direct tumor xenograft platform. We have identified and
characterized six cancer cell subpopulations each clonally expanded from a single
cell, derived from human ovarian clear cell carcinoma of a single tumor, to
demonstrate striking intratumoral phenotypic heterogeneity that is dynamically
dependent on the tumor growth microenvironment. These cancer cell subpopulations,
characterized as cancer stem cell subpopulations, faithfully recapitulate the
full spectrum of histological phenotypic heterogeneity known for human ovarian
clear cell carcinoma. Each of the six subpopulations displays a different level
of morphologic and tumorigenic differentiation wherein growth in the hESC-derived
microenvironment favors growth of CD44+/aldehyde dehydrogenase positive pockets
of self-renewing cells that sustain tumor growth through a process of tumorigenic
differentiation into CD44-/aldehyde dehydrogenase negative derivatives.
Strikingly, these derivative cells display microenvironment-dependent plasticity
with the capacity to restore self-renewal markers and CD44 expression. In the
current study, we delineate the distinct gene expression and epigenetic profiles
of two such subpopulations, representing extremes of phenotypic heterogeneity in
terms of niche-dependent self-renewal and tumorigenic differentiation. By
combining Gene Set Enrichment, Gene Ontology and Pathway-focused array analyses
with methylation status, we propose a suite of robust differences in tumor self
renewal and differentiation pathways that underlie the striking intratumoral
phenotypic heterogeneity which characterize this and other solid tumor
malignancies.
PMID- 24358305
TI - Mucus properties and goblet cell quantification in mouse, rat and human ileal
Peyer's patches.
AB - Peyer's patches (PPs) are collections of lymphoid follicles in the small
intestine, responsible for scanning the intestinal content for foreign antigens
such as soluble molecules, particulate matter as well as intact bacteria and
viruses. The immune cells of the patch are separated from the intestinal lumen by
a single layer of epithelial cells, the follicle-associated epithelium (FAE).
This epithelium covers the dome of the follicle and contains enterocyte-like
cells and M cells, which are particularly specialized in taking up antigens from
the gut. However, the presence and number of goblet cells as well as the presence
of mucus on top of the FAE is controversial. When mouse ileal PPs were mounted in
a horizontal Ussing-type chamber, we could observe a continuous mucus layer at
mounting and new, easily removable mucus was released from the villi on the patch
upon stimulation. Confocal imaging using fluorescent beads revealed a penetrable
mucus layer covering the domes. Furthermore, immunostaining of FAE from mice,
rats and humans with a specific antibody against the main component of intestinal
mucus, the MUC2 mucin, clearly identify mucin-containing goblet cells.
Transmission electron micrographs further support the identification of mucus
releasing goblet cells on the domes of PPs in these species.
PMID- 24358306
TI - The impact of a diabetes local enhanced service on quality outcome framework
diabetes outcomes.
AB - BACKGROUND: The rising challenge of diabetes requires novel service delivery
approaches. In the UK, Local Enhanced Services (LES) have been commissioned for
diabetes. Health professionals from general practices (GPs) who signed up to LES
were given additional training (and a monetary incentive) to improve management
of patients with diabetes. All practices in the PCT were invited to the LES
initiative, which ensured avoiding selection bias. The aim of the study was to
examine the impact of LES in terms of diabetes Quality Outcome Framework (QOF)
indicators: DM23(glycaemia), DM17(lipid) and DM12(blood pressure; BP). METHODS:
QOF diabetes indicators were examined using data from 76 general practices for
2009-2010 in a large primary care trust area in Birmingham, UK. Data were
extracted from Quality Management Analysis System. The primary outcome was a
difference in achievement of QOF indicators between LES and NLES practices. A
secondary outcome was the difference between LES and non-LES practices for
hospital first and follow-up appointments. RESULTS: We did not find any
difference for DM12(BP) and DM17(lipid) outcomes between LES and NLES practices.
However, LES practices were more likely to achieve the DM23(glycaemia) outcome
(estimated odds 1.459;95% CI:1.378-1.544; P=0.0001). The probability of achieving
satisfactory level of DM23(glycaemia) increased by almost 10% when GPs belonged
to LES groups compared with GPs in NLES group. LES practices were less likely to
refer patients to secondary care. CONCLUSION: Overall, LES practices performed
better in the achievement of DM23(glycaemia) and also referred fewer patients to
hospital, thereby meeting their objectives. This suggests that the LES approach
is beneficial and needs to be further explored in order to ascertain whether the
impact exerted was due to LES.
PMID- 24358307
TI - Characterization of the SigD regulon of C. difficile and its positive control of
toxin production through the regulation of tcdR.
AB - Clostridium difficile intestinal disease is mediated largely by the actions of
toxins A (TcdA) and B (TcdB), whose production occurs after the initial steps of
colonization involving different surface or flagellar proteins. In B. subtilis,
the sigma factor SigD controls flagellar synthesis, motility, and vegetative
autolysins. A homolog of SigD encoding gene is present in the C.difficile 630
genome. We constructed a sigD mutant in C. difficile 630 ?erm to analyze the
regulon of SigD using a global transcriptomic approach. A total of 103 genes were
differentially expressed between the wild-type and the sigD mutant, including
genes involved in motility, metabolism and regulation. In addition, the sigD
mutant displayed decreased expression of genes involved in flagellar
biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the
positive regulator of the toxins. Genomic analysis and RACE-PCR experiments
allowed us to characterize promoter sequences of direct target genes of SigD
including tcdR and to identify the SigD consensus. We then established that SigD
positively regulates toxin expression via direct control of tcdR transcription.
Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited
the positive regulation of motility and toxin synthesis by SigD. Thus, SigD
appears to be the first positive regulator of the toxin synthesis in C.
difficile.
PMID- 24358308
TI - A metabolomic analysis of omega-3 fatty acid-mediated attenuation of western diet
induced nonalcoholic steatohepatitis in LDLR-/- mice.
AB - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive form of
nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular
carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic
acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n
3) at reversing western diet (WD) induced NASH in LDLR(-/-) mice. METHODS: Using
livers from our previous study, we carried out a global non-targeted metabolomic
approach to quantify diet-induced changes in hepatic metabolism. RESULTS: Livers
from WD + olive oil (WD + O)-fed mice displayed histological and gene expression
features consistent with NASH. The metabolomic analysis of 320 metabolites
established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation
had broad effects on all major metabolic pathways. Livers from WD + O-fed mice
were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA),
palmitoyl-sphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing
phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of
C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized
lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal
detoxification product. WD + DHA was more effective than WD + EPA at attenuating
WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized
lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA
and sphingolipid content were associated with changes in expression of enzymes
involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty
acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20
22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with
hepatic alpha-tocopherol and ascorbate content and positively associated with
urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative
stress. CONCLUSION: DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin,
PUFA-derived oxidized lipids and S-lactoylglutathione may explain the protective
effects of DHA against WD-induced NASH in LDLR(-/-) mice.
PMID- 24358309
TI - A universal method for species identification of mammals utilizing next
generation sequencing for the analysis of DNA mixtures.
AB - Species identification can be interesting in a wide range of areas, for example,
in forensic applications, food monitoring and in archeology. The vast majority of
existing DNA typing methods developed for species determination, mainly focuses
on a single species source. There are, however, many instances where all species
from mixed sources need to be determined, even when the species in minority
constitutes less than 1 % of the sample. The introduction of next generation
sequencing opens new possibilities for such challenging samples. In this study we
present a universal deep sequencing method using 454 GS Junior sequencing of a
target on the mitochondrial gene 16S rRNA. The method was designed through
phylogenetic analyses of DNA reference sequences from more than 300 mammal
species. Experiments were performed on artificial species-species mixture samples
in order to verify the method's robustness and its ability to detect all species
within a mixture. The method was also tested on samples from authentic forensic
casework. The results showed to be promising, discriminating over 99.9 % of
mammal species and the ability to detect multiple donors within a mixture and
also to detect minor components as low as 1 % of a mixed sample.
PMID- 24358310
TI - Soluble expression of human leukemia inhibitory factor with protein disulfide
isomerase in Escherichia coli and its simple purification.
AB - Human leukemia inhibitory factor (hLIF) is a multifunctional cytokine that is
essential for maintaining the pluripotency of embryonic stem cells. hLIF may be
also be useful in aiding fertility through its effects on increasing the
implantation rate of fertilized eggs. Thus these applications in biomedical
research and clinical medicine create a high demand for bioactive hLIF. However,
production of active hLIF is problematic since eukaryotic cells demonstrate
limited expression and prokaryotic cells produce insoluble protein. Here, we have
adopted a hybrid protein disulfide isomerase design to increase the solubility of
hLIF in Escherichia coli. Low temperature expression of hLIF fused to the b'a'
domain of protein disulfide isomerase (PDIb'a') increased the soluble expression
in comparison to controls. A simple purification protocol for bioactive hLIF was
established that includes removal of the PDIb'a' domain by cleavage by TEV
protease. The resulting hLIF, which contains one extra glycine residue at the N
terminus, was highly pure and demonstrated endotoxin levels below 0.05 EU/MUg.
The presence of an intramolecular disulfide bond was identified using mass
spectroscopy. This purified hLIF effectively maintained the pluripotency of a
murine embryonic stem cell line. Thus we have developed an effective method to
produce a pure bioactive version of hLIF in E. coli for use in biomedical
research.
PMID- 24358311
TI - ERK2-mediated phosphorylation of transcriptional coactivator binding protein
PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis.
AB - PRIP-Interacting protein with methyl transferase domain (PIMT) serves as a
molecular bridge between CREB-binding protein (CBP)/ E1A binding protein p300
(Ep300) -anchored histone acetyl transferase and the Mediator complex sub-unit1
(Med1) and modulates nuclear receptor transcription. Here, we report that ERK2
phosphorylates PIMT at Ser(298) and enhances its ability to activate PEPCK
promoter. We observed that PIMT is recruited to PEPCK promoter and adenoviral
mediated over-expression of PIMT in rat primary hepatocytes up-regulated
expression of gluconeogenic genes including PEPCK. Reporter experiments with
phosphomimetic PIMT mutant (PIMT(S298D)) suggested that conformational change may
play an important role in PIMT-dependent PEPCK promoter activity. Overexpression
of PIMT and Med1 together augmented hepatic glucose output in an additive manner.
Importantly, expression of gluconeogenic genes and hepatic glucose output were
suppressed in isolated liver specific PIMT knockout mouse hepatocytes.
Furthermore, consistent with reporter experiments, PIMT(S298D) but not
PIMT(S298A) augmented hepatic glucose output via up-regulating the expression of
gluconeogenic genes. Pharmacological blockade of MAPK/ERK pathway using U0126,
abolished PIMT/Med1-dependent gluconeogenic program leading to reduced hepatic
glucose output. Further, systemic administration of T4 hormone to rats activated
ERK1/2 resulting in enhanced PIMT ser(298) phosphorylation. Phosphorylation of
PIMT led to its increased binding to the PEPCK promoter, increased PEPCK
expression and induction of gluconeogenesis in liver. Thus, ERK2-mediated
phosphorylation of PIMT at Ser(298) is essential in hepatic gluconeogenesis,
demonstrating an important role of PIMT in the pathogenesis of hyperglycemia.
PMID- 24358313
TI - Spatio-temporal variation in vegetation biomass and its relationships with
climate factors in the Xilingol grasslands, Northern China.
AB - Knowledge about grassland biomass and its dynamics is critical for studying
regional carbon cycles and for the sustainable use of grassland resources. In
this study, we investigated the spatio-temporal variation of biomass in the
Xilingol grasslands of northern China. Field-based biomass samples and MODIS time
series data sets were used to establish two empirical models based on the
relationship of the normalized difference vegetation index (NDVI) with above
ground biomass (AGB) as well as that of AGB with below-ground biomass (BGB). We
further explored the climatic controls of these variations. Our results showed
that the biomass averaged 99.01 Tg (1 Tg=10(12) g) over a total area of 19.6 *
10(4) km(2) and fluctuated with no significant trend from 2001 to 2012. The mean
biomass density was 505.4 g/m(2), with 62.6 g/m(2) in AGB and 442.8 g/m(2) in
BGB, which generally decreased from northeast to southwest and exhibited a large
spatial heterogeneity. The year-to-year AGB pattern was generally consistent with
the inter-annual variation in the growing season precipitation (GSP), showing a
robust positive correlation (R(2)=0.82, P<0.001), but an opposite coupled pattern
was observed with the growing season temperature (GST) (R(2)=0.61, P=0.003).
Climatic factors also affected the spatial distribution of AGB, which increased
progressively with the GSP gradient (R(2)=0.76, P<0.0001) but decreased with an
increasing GST (R(2)=0.70, P<0.0001). An improved moisture index that combined
the effects of GST and GSP explained more variation in AGB than did precipitation
alone (R(2)=0.81, P<0.0001). The relationship between AGB and GSP could be fit by
a power function. This increasing slope of the GSP-AGB relationships along the
GSP gradient may be partly explained by the GST-GSP spatial pattern in Xilingol.
Our findings suggest that the relationships between climatic factors and AGB may
be scale-dependent and that multi-scale studies and sufficient long-term field
data are needed to examine the relationships between AGB and climatic factors.
PMID- 24358312
TI - Gender differences of brain glucose metabolic networks revealed by FDG-PET:
evidence from a large cohort of 400 young adults.
AB - BACKGROUND: Gender differences of the human brain are an important issue in
neuroscience research. In recent years, an increasing amount of evidence has been
gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of
the human brain. However, there is a lack of imaging studies on gender
differences of brain metabolic networks based on a large population sample.
MATERIALS AND METHODS: FDG PET data of 400 right-handed, healthy subjects,
including 200 females (age: 25:45 years, mean age +/- SD: 40.9 +/- 3.9 years) and
200 age-matched males were obtained and analyzed in the present study. We first
investigated the regional differences of brain glucose metabolism between genders
using a voxel-based two-sample t-test analysis. Subsequently, we investigated the
gender differences of the metabolic networks. Sixteen metabolic covariance
networks using seed-based correlation were analyzed. Seven regions showing
significant regional metabolic differences between genders, and nine regions
conventionally used in the resting-state network studies were selected as regions
of-interest. Permutation tests were used for comparing within- and between
network connectivity between genders. RESULTS: Compared with the males, females
showed higher metabolism in the posterior part and lower metabolism in the
anterior part of the brain. Moreover, there were widely distributed patterns of
the metabolic networks in the human brain. In addition, significant gender
differences within and between brain glucose metabolic networks were revealed in
the present study. CONCLUSION: This study provides solid data that reveal gender
differences in regional brain glucose metabolism and brain glucose metabolic
networks. These observations might contribute to the better understanding of the
gender differences in human brain functions, and suggest that gender should be
included as a covariate when designing experiments and explaining results of
brain glucose metabolic networks in the control and experimental individuals or
patients.
PMID- 24358314
TI - Development of non-profit organisations providing health and social services in
rural South Africa: a three-year longitudinal study.
AB - INTRODUCTION: In an effort to increase understanding of formation of the
community and home-based care economy in South Africa, we investigated the origin
and development of non-profit organisations (NPOs) providing home- and community
based care for health and social services in a remote rural area of South Africa.
METHODS: Over a three-year period (2010-12), we identified and tracked all NPOs
providing health care and social services in Bushbuckridge sub-district through
the use of local government records, snowballing techniques, and attendance at
NPO networking meetings--recording both existing and new NPOs. NPO founders and
managers were interviewed in face-to-face in-depth interviews, and their
organisational records were reviewed. RESULTS: Forty-seven NPOs were formed prior
to the study period, and 14 during the study period--six in 2010, six in 2011 and
two in 2012, while four ceased operation, representing a 22% growth in the number
of NPOs during the study period. Histories of NPOs showed a steady rise in the
NPO formation over a 20-year period, from one (1991-1995) to 12 (1996-2000), 16
(2001-2005) and 24 (2006-2010) new organisations formed in each period.
Furthermore, the histories of formation revealed three predominant milestones-
loose association, formal formation and finally registration. Just over one
quarter (28%) of NPOs emerged from a long-standing community based programme of
'care groups' of women. Founders of NPOs were mostly women (62%), with either a
religious motivation or a nursing background, but occasionally had an
entrepreneurial profile. CONCLUSION: We observed rapid growth of the NPO sector
providing community based health and social services. Women dominated the rural
NPO sector, which is being seen as creating occupation and employment
opportunities. The implications of this growth in the NPO sector providing
community based health and social services needs to be further explored and
suggests the need for greater coordination and possibly regulation.
PMID- 24358315
TI - C-terminal domain of ICA69 interacts with PICK1 and acts on trafficking of PICK1
PKCalpha complex and cerebellar plasticity.
AB - BACKGROUND: PICK1 (protein interacting with C-kinase 1) is a PKC (protein kinase
C)-binding protein, which is essential for synaptic plasticity. The trafficking
of PKCalpha-PICK1 complex to plasma membrane is critical for the internalization
of GluR2 and induction of long-term depression. ICA69 (islet cell autoantigen 69
kDa) is identified as a major binding partner of PICK1. While heteromeric BAR
domain complex is suggested to underlie the interaction between PICK1 and ICA69,
the role of C-terminal domain of ICA69 (ICAC) in PICK1-ICA69 complex is unknown.
METHODOLOGY/PRINCIPAL FINDINGS: We found that ICAC interacted with PICK1 and
regulated the trafficking of PICK1-PKCalpha complex. ICAC and DeltaICAC
(containing BAR domain) might function distinctly in the association of ICA69
with PICK1. While DeltaICAC domain inclined to form clusters, the distribution of
ICAC was diffuse. The trafficking of PICK1 to plasma membrane mediated by
activated PKCalpha was inhibited by ICA69. This action might ascribe to ICAC,
because overexpression of ICAC, but not DeltaICAC, interrupted PKCalpha-mediated
PICK1 trafficking. Notably, infusion of maltose binding protein (MBP) fusion
protein, MBP-ICA69 or MBP-ICAC, in cerebellar Purkinje cells significantly
inhibited the induction of long-term depression at parallel fiber- and climbing
fiber-Purkinje cell synapses. CONCLUSIONS: Our experiments showed that ICAC is an
important domain for the ICA69-PICK1 interaction and plays essential roles in
PICK1-mediated neuronal plasticity.
PMID- 24358316
TI - Co-residence between males and their mothers and grandmothers is more frequent in
bonobos than chimpanzees.
AB - In long-lived social mammals such as primates, individuals can benefit from
social bonds with close kin, including their mothers. In the patrilocal
chimpanzee (Pan troglodytes spp.) and bonobo (Pan paniscus), sexually mature
males reside and reproduce in their natal groups and can retain post-dependency
bonds with their mothers, while immatures of both sexes might also have their
paternal grandmothers available. However, quantitative information on the
proportion of males and immatures that co-reside with both types of these close
female relatives is limited for both species. Combining genetic parentage
determination and group composition data from five communities of wild
chimpanzees and three communities of wild bonobos, we estimated the frequency of
co-residence between (1) mature males and their mothers, and (2) immature males
and females and their paternal grandmothers. We found that adult males resided
twice as frequently with their mothers in bonobos than in chimpanzees, and that
immature bonobos were three times more likely to possess a living paternal
grandmother than were immature chimpanzees. Patterns of female and male
survivorship from studbook records of captive individuals of both species suggest
that mature bonobo females survive longer than their chimpanzee counterparts,
possibly contributing to the differences observed in mother-son and grandmother
immature co-residency levels. Taking into account reports of bonobo mothers
supporting their sons' mating efforts and females sharing food with immatures
other than their own offspring, our findings suggest that life history traits may
facilitate maternal and grandmaternal support more in bonobos than in
chimpanzees.
PMID- 24358317
TI - Effects of reticuloendotheliosis virus infection on cytokine production in SPF
chickens.
AB - Infection with reticuloendotheliosis virus (REV), a gammaretrovirus in the
Retroviridae family, can result in immunosuppression and subsequent increased
susceptibility to secondary infections. The effects of REV infection on
expression of mRNA for cytokine genes in chickens have not been completely
elucidated. In this study, using multiplex branched DNA (bDNA) technology, we
identified molecular mediators that participated in the regulation of the immune
response during REV infection in chickens. Cytokine and chemokine mRNA expression
levels were evaluated in the peripheral blood mononuclear cells (PBMCs).
Expression levels of interleukin (IL)-4, IL-10, IL-13 and tumor necrosis factor
(TNF)-alpha were significantly up-regulated while interferon (IFN)-alpha, IFN
beta, IFN-gamma, IL-1beta, IL-2, IL-3, IL-15, IL-17F, IL-18 and colony
stimulating factor (CSF)-1 were markedly decreased in PBMCs at all stages of
infection. Compared with controls, REV infected chickens showed greater
expression levels of IL-8 in PBMCs 21 and 28 days post infection. In addition,
REV regulates host immunity as a suppressor of T cell proliferative responses.
The results in this study will help us to understand the host immune response to
virus pathogens.
PMID- 24358318
TI - The role of non-curative surgery in incurable, asymptomatic advanced gastric
cancer.
AB - BACKGROUND: Although general agreement exists on palliative surgery with intent
of symptom palliation in advanced gastric cancer (AGC), the role of non-curative
surgery for incurable, asymptomatic AGC is hotly debated. We aim to clarify the
role of non-curative surgery in patients with incurable, asymptomatic AGC under
the first-line chemotherapy. METHODS: A total of 737 patients with incurable,
asymptomatic advanced gastric adenocarcinoma between January 2008 and May 2012 at
the Sun Yat-sen University Cancer Center were retrospectively analyzed,
comprising 414 patients with non-curative surgery plus first-line chemotherapy,
and 323 patients with first-line chemotherapy only. The clinicopathologic data,
survival, and prognosis were evaluated, with propensity score adjustment for
selection bias. RESULTS: The median overall survival (OS) outcomes significantly
favored non-curative surgery group over first-line chemotherapy only group in
entire population (28.00 versus 10.37 months, P = 0.000), stage 4 patients (23.87
versus 10.37 months, P = 0.000), young patients (28.70 versus 10.37 months, P =
0.000) and elderly patients (23.07 versus 10.27 months, P = 0.031). The median OS
advantages of non-curative surgery over first-line chemotherapy only were also
maintained when the analyses were restricted to single organ metastasis (P =
0.001), distant lymph node metastasis (P = 0.002), peritoneal metastasis (P =
0.000), and multi-organ metastasis (P = 0.010). Significant OS advantages of non
curative surgery over chemotherapy only were confirmed solid by multivariate
analyses before and after adjustment on propensity score (P = 0.000). Small
subsets of patients with surgery of single metastatic lesion after previous
curative gastrectomy, and with surgery of both primary and single metastatic
sites showed sound median OS. CONCLUSIONS: There is a role for non-curative
surgery plus first-line chemotherapy for incurable, asymptomatic AGC, in terms of
survival. Randomized controlled trials are warranted to fill a gap in knowledge
about the value of metastectomy and patient selection strategies.
PMID- 24358319
TI - Use of indocyanine green for detecting the sentinel lymph node in breast cancer
patients: from preclinical evaluation to clinical validation.
AB - Assessment of the sentinel lymph node (SLN) in patients with early stage breast
cancer is vital in selecting the appropriate surgical approach. However, the
existing methods, including methylene blue and nuclides, possess low efficiency
and effectiveness in mapping SLNs, and to a certain extent exert side effects
during application. Indocyanine green (ICG), as a fluorescent dye, has been
proved reliable usage in SLN detection by several other groups. In this paper, we
introduce a novel surgical navigation system to detect SLN with ICG. This system
contains two charge-coupled devices (CCD) to simultaneously capture real-time
color and fluorescent video images through two different bands. During surgery,
surgeons only need to follow the fluorescence display. In addition, the system
saves data automatically during surgery enabling surgeons to find the
registration point easily according to image recognition algorithms. To test our
system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast
cancer patients were utilized for the clinical evaluation in our experiments. The
detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our
results show that the usage of our surgical navigation system with ICG to detect
SLNs in breast cancer patients is technically feasible.
PMID- 24358320
TI - Morphologic and functional connectivity alterations of corticostriatal and
default mode network in treatment-naive patients with obsessive-compulsive
disorder.
AB - BACKGROUND: Previous studies have demonstrated that structural deficits and
functional connectivity imbalances might underlie the pathophysiology of
obsessive-compulsive disorder (OCD). The purpose of the present study was to
investigate gray matter deficits and abnormal resting-state networks in patients
with OCD and further investigate the association between the anatomic and
functional alterations and clinical symptoms. METHODS: Participants were 33
treatment-naive OCD patients and 33 matched healthy controls. Voxel-based
morphometry was used to investigate the regions with gray matter abnormalities
and resting-state functional connectivity analysis was further conducted between
each gray matter abnormal region and the remaining voxels in the brain. RESULTS:
Compared with healthy controls, patients with OCD showed significantly increased
gray matter volume in the left caudate, left thalamus, and posterior cingulate
cortex, as well as decreased gray matter volume in the bilateral medial
orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal
gyrus. By using the above morphologic deficits areas as seed regions, functional
connectivity analysis found abnormal functional integration in the cortical
striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent
correlation analyses revealed that morphologic deficits in the left thalamus and
increased functional connectivity within the CSTC circuits positively correlated
with the total Y-BOCS score. CONCLUSION: This study provides evidence that
morphologic and functional alterations are seen in CSTC circuits and default mode
network in treatment-naive OCD patients. The association between symptom severity
and the CSTC circuits suggests that anatomic and functional alterations in CSTC
circuits are especially important in the pathophysiology of OCD.
PMID- 24358321
TI - Photoresist-free patterning by mechanical abrasion of water-soluble lift-off
resists and bare substrates: toward green fabrication of transparent electrodes.
AB - This paper describes the fabrication of transparent electrodes based on grids of
copper microwires using a non-photolithographic process. The process--"abrasion
lithography"--takes two forms. In the first implementation (Method I), a water
soluble commodity polymer film is abraded with a sharp tool, coated with a
conductive film, and developed by immersion in water. Water dissolves the polymer
film and lifts off the conductive film in the unabraded areas. In the second
implementation (Method II), the substrate is abraded directly by scratching with
a sharp tool (i.e., no polymer film necessary). The abraded regions of the
substrate are recessed and roughened. Following deposition of a conductive film,
the lower profile and roughened topography in the abraded regions prevents
mechanical exfoliation of the conductive film using adhesive tape, and thus the
conductive film remains only where the substrate is scratched. As an application,
conductive grids exhibit average sheet resistances of 17 Omega sq(-1) and
transparencies of 86% are fabricated and used as the anode in organic
photovoltaic cells in concert with the conductive polymer, poly(3,4
ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). Compared to devices
in which PEDOT:PSS alone serves as an anode, devices comprising grids of
copper/nickel microwires and PEDOT:PSS exhibit lowered series resistance, which
manifests in greater fill factor and power conversion efficiency. This simple
method of forming micropatterns could find use in applications where cost and
environmental impact should be minimized, especially as a potential replacement
for the transparent electrode indium tin oxide (ITO) in thin-film electronics
over large areas (i.e., solar cells) or as a method of rapid prototyping for
laboratory-scale devices.
PMID- 24358322
TI - Efficient modeling and active learning discovery of biological responses.
AB - High throughput and high content screening involve determination of the effect of
many compounds on a given target. As currently practiced, screening for each new
target typically makes little use of information from screens of prior targets.
Further, choices of compounds to advance to drug development are made without
significant screening against off-target effects. The overall drug development
process could be made more effective, as well as less expensive and time
consuming, if potential effects of all compounds on all possible targets could be
considered, yet the cost of such full experimentation would be prohibitive. In
this paper, we describe a potential solution: probabilistic models that can be
used to predict results for unmeasured combinations, and active learning
algorithms for efficiently selecting which experiments to perform in order to
build those models and determining when to stop. Using simulated and experimental
data, we show that our approaches can produce powerful predictive models without
exhaustive experimentation and can learn them much faster than by selecting
experiments at random.
PMID- 24358323
TI - Whole blood gene expression profiles in insulin resistant Latinos with the
metabolic syndrome.
AB - Although insulin resistance in skeletal muscle is well-characterized, the role of
circulating whole blood in the metabolic syndrome phenotype is not well
understood. We set out to test the hypothesis that genes involved in
inflammation, insulin signaling and mitochondrial function would be altered in
expression in the whole blood of individuals with metabolic syndrome. We further
wanted to examine whether similar relationships that we have found previously in
skeletal muscle exist in peripheral whole blood cells. All subjects (n=184) were
Latino descent from the Arizona Insulin Resistance registry. Subjects were
classified based on the metabolic syndrome phenotype according to the National
Cholesterol Education Program's Adult Treatment Panel III. Of the 184 Latino
subjects in the study, 74 were classified with the metabolic syndrome and 110
were without. Whole blood gene expression profiling was performed using the
Agilent 4x44K Whole Human Genome Microarray. Whole blood microarray analysis
identified 1,432 probes that were altered in expression >= 1.2 fold and P<0.05
after Benjamini-Hochberg in the metabolic syndrome subjects. KEGG pathway
analysis revealed significant enrichment for pathways including ribosome,
oxidative phosphorylation and MAPK signaling (all Benjamini-Hochberg P<0.05).
Whole blood mRNA expression changes observed in the microarray data were
confirmed by quantitative RT-PCR. Transcription factor binding motif enrichment
analysis revealed E2F1, ELK1, NF-kappaB, STAT1 and STAT3 significantly enriched
after Bonferroni correction (all P<0.05). The results of the present study
demonstrate that whole blood is a useful tissue for studying the metabolic
syndrome and its underlying insulin resistance although the relationship between
blood and skeletal muscle differs.
PMID- 24358324
TI - Relationship status and relationship instability, but not dominance, predict
individual differences in baseline cortisol levels.
AB - We investigated variation in baseline cortisol levels in relation to relationship
status (single or in a relationship), relationship characteristics (length,
stability, presence or absence of clear dominance), or individual attributes
(dominant or subordinate status, relative physical attractiveness, relationship
worries). Study participants were 77 men and 75 women aged between 18 and 38
years. Individuals in romantic relationships had lower cortisol levels than
singles. Individuals of African ethnicity, however, showed the opposite pattern.
Individuals who perceived their relationship to be highly unstable had higher
cortisol levels. Aside from African-Americans, married individuals reported the
lowest relationship instability and the lowest cortisol levels, followed by
individuals in long-term relationships, and by individuals in short-term
relationships. The presence or absence of clear dominance in the relationship,
dominance status, or relationship worries did not affect cortisol levels.
Therefore relationship status and relationship instability were better predictors
of variation in cortisol (presumably through stress-related mechanisms) than
individual attributes.
PMID- 24358325
TI - Neuroscientists' classroom visits positively impact student attitudes.
AB - The primary recommendation of the 2010 President's Council of Advisors on Science
and Technology report on K-12 education was to inspire more students so that they
are motivated to study science. Scientists' visits to classrooms are intended to
inspire learners and increase their interest in science, but verifications of
this impact are largely qualitative. Our primary goal was to evaluate the impact
of a longstanding Brain Awareness classroom visit program focused on increasing
learners understanding of their own brains. Educational psychologists have
established that neuroscience training sessions can improve academic performance
and shift attitudes of students from a fixed mindset to a growth mindset. Our
secondary goal was to determine whether short interactive Brain Awareness
scientist-in-the-classroom sessions could similarly alter learners' perceptions
of their own potential to learn. Teacher and student surveys were administered in
4(th)-6(th) grade classrooms throughout Minnesota either before or after one-hour
Brain Awareness sessions that engaged students in activities related to brain
function. Teachers rated the Brain Awareness program as very valuable and said
that the visits stimulated students' interest in the brain and in science.
Student surveys probed general attitudes towards science and their knowledge of
neuroscience concepts (particularly the ability of the brain to change).
Significant favorable improvements were found on 10 of 18 survey statements.
Factor analyses of 4805 responses demonstrated that Brain Awareness presentations
increased positive attitudes toward science and improved agreement with
statements related to growth mindset. Overall effect sizes were small, consistent
with the short length of the presentations. Thus, the impact of Brain Awareness
presentations was positive and proportional to the efforts expended,
demonstrating that short, scientist-in-the-classroom visits can make a positive
contribution to primary school students' attitudes toward science and learning.
PMID- 24358326
TI - Genetic background alters the severity and onset of neuromuscular disease caused
by the loss of ubiquitin-specific protease 14 (usp14).
AB - In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU)
induced mutation in Usp14 (nmf375) that leads to adult-onset neurological
disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in
a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax
(J)) mice results in reduced ubiquitin levels, motor endplate disease, Purkinje
cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF)
during the first 4-6 weeks of life, and early postnatal lethality by two months
of age. Although the loss of USP14 is comparable between the nmf375 and ax (J)
mice, the nmf375 mice did not exhibit these ax (J) developmental abnormalities.
However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion
and motor endplate disease, indicating a continual role for USP14-mediated
regulation of ubiquitin pools and neuromuscular junction (NMJ) structure in adult
mice. The observation that motor endplate disease was only seen after ubiquitin
depletion suggests that the preservation of NMJ structure requires the stable
maintenance of synaptic ubiquitin pools. Differences in genetic background were
shown to affect ubiquitin expression and dramatically alter the phenotypes caused
by USP14 deficiency.
PMID- 24358327
TI - Neuroanatomical heterogeneity of essential tremor according to propranolol
response.
AB - BACKGROUND: Recent studies have suggested that essential tremor (ET) is a more
complex and heterogeneous clinical entity than initially thought. In the present
study, we assessed the pattern of cortical thickness and diffusion tensor white
matter (WM) changes in patients with ET according to the response to propranolol
to explore the pathogenesis underlying the clinical heterogeneity of ET. METHODS:
A total of 32 patients with drug naive ET were recruited prospectively from the
Movement Disorders outpatient clinic. The patients were divided into a
propranolol-responder group (n = 18) and a non-responder group (n = 14). We
analyzed the pattern of cortical thickness and diffusion tensor WM changes
between these two groups and performed correlation analysis between imaging and
clinical parameters. RESULTS: There were no significant differences in
demographic characteristics, general cognition, or results of detailed
neuropsychological tests between the groups. The non-responder group showed more
severe cortical atrophy in the left orbitofrontal cortex and right temporal
cortex relative to responders. However, the responders exhibited significantly
lower fractional anisotropy values in the bilateral frontal, corpus callosal, and
right parietotemporal WM compared with the non-responder group. There were no
significant clusters where the cortical thickness or WM alterations were
significantly correlated with initial tremor severity or disease duration.
CONCLUSIONS: The present data suggest that patients with ET have heterogeneous
cortical thinning and WM alteration with respect to responsiveness to
propranolol, suggesting that propranolol responsiveness may be a predictive
factor to determine ET subtypes in terms of neuroanatomical heterogeneity.
PMID- 24358328
TI - Gene expression profiling of early hepatic stellate cell activation reveals a
role for Igfbp3 in cell migration.
AB - BACKGROUND: Scarring of the liver is the result of prolonged exposure to
exogenous or endogenous stimuli. At the onset of fibrosis, quiescent hepatic
stellate cells (HSCs) activate and transdifferentiate into matrix producing,
myofibroblast-like cells. AIM AND METHODS: To identify key players during early
HSC activation, gene expression profiling was performed on primary mouse HSCs
cultured for 4, 16 and 64 hours. Since valproic acid (VPA) can partly inhibit HSC
activation, we included VPA-treated cells in the profiling experiments to
facilitate this search. RESULTS: Gene expression profiling confirmed early
changes for known genes related to HSC activation such as alpha smooth muscle
actin (Acta2), lysyl oxidase (Lox) and collagen, type I, alpha 1 (Col1a1). In
addition we noticed that, although genes which are related to fibrosis change
between 4 and 16 hours in culture, most gene expression changes occur between 16
and 64 hours. Insulin-like growth factor binding protein 3 (Igfbp3) was
identified as a gene strongly affected by VPA treatment. During normal HSC
activation Igfbp3 is up regulated and this can thus be prevented by VPA treatment
in vitro and in vivo. siRNA-mediated silencing of Igfbp3 in primary mouse HSCs
induced matrix metalloproteinase (Mmp) 9 mRNA expression and strongly reduced
cell migration. The reduced cell migration after Igfbp3 knock-down could be
overcome by tissue inhibitor of metalloproteinase (TIMP) 1 treatment. CONCLUSION:
Igfbp3 is a marker for culture-activated HSCs and plays a role in HSC migration.
VPA treatment prevents Igfbp3 transcription during activation of HSCs in vitro
and in vivo.
PMID- 24358329
TI - Momordica charantia (Bitter Melon) reduces obesity-associated macrophage and mast
cell infiltration as well as inflammatory cytokine expression in adipose tissues.
AB - Obesity is a world-wide epidemic disease that correlates closely with type 2
diabetes and cardiovascular diseases. Obesity-induced chronic adipose tissue
inflammation is now considered as a critical contributor to the above
complications. Momordica charantia (bitter melon, BM) is a traditional Chinese
food and well known for its function of reducing body weight gain and insulin
resistance. However, it is unclear whether BM could alleviate adipose tissue
inflammation caused by obesity. In this study, C57BL/6 mice were fed high fat
diet (HFD) with or without BM for 12 weeks. BM-contained diets ameliorated HFD
induced obesity and insulin resistance. Histological and real-time PCR analysis
demonstrated BM not only reduced macrophage infiltration into epididymal adipose
tissues (EAT) and brown adipose tissues (BAT). Flow cytometry show that BM could
modify the M1/M2 phenotype ratio of macrophages in EAT. Further study showed that
BM lowered mast cell recruitments in EAT, and depressed pro-inflammatory cytokine
monocyte chemotactic protein-1 (MCP-1) expression in EAT and BAT as well as
interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression in
EAT. Finally, ELISA analysis showed BM-contained diets also normalized serum
levels of the cytokines. In summary, in concert with ameliorated insulin
resistance and fat deposition, BM reduced adipose tissue inflammation in diet
induced obese (DIO) mice.
PMID- 24358330
TI - Normalization of ventilation data from 4D-CT to facilitate comparison between
datasets acquired at different times.
AB - PURPOSE: The 4D-CT data used for comparing a patient's ventilation distributions
before and after lung radiotherapy are acquired at different times. As a result,
an additional variable--the tidal volume (TV)--can alter the results. Therefore,
in this paper we propose to normalize the ventilation to the same TV to eliminate
that uncertainty. METHODS: Absolute ventilation (AV) data were generated for 6
stereotactic body radiation therapy (SBRT) cases before and after treatment,
using the direct geometric algorithm and diffeomorphic morphons deformable image
registration (DIR). Each pair of AV distributions was converted to TV-normalized,
percentile ventilation (PV) and low-dose well-ventilated-normalized ventilation
(LDWV) distributions. The ventilation change was calculated in various dose
regions based on the treatment plans using the DIR-registered before and after
treatment data sets. The ventilation change based on TV-normalized ventilation
was compared with the AV as well as the data normalized by PV and LDWV. RESULTS:
AV change may be misleading when the TV differs before and after treatment, which
was found to be up to 6.7%. All three normalization methods produced a similar
trend in ventilation change: the higher the dose to a region of lung, the greater
the degradation in ventilation. In low dose regions (<5 Gy), ventilation appears
relatively improved after treatment due to the relative nature of the normalized
ventilation. However, the LDWV may not be reliable when the ventilation in the
low-dose regions varies. PV exhibited a similar ventilation change trend compared
to the TV-normalized in all cases. However, by definition, the ventilation
distribution in the PV is significantly different from the original distribution.
CONCLUSION: Normalizing ventilation distributions by the TV is a simple and
reliable method for evaluation of ventilation changes.
PMID- 24358331
TI - A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa
inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in
macrophages.
AB - Several diterpenoids isolated from terrestrial and marine environments have been
identified as important anti-inflammatory agents. Although considerable progress
has been made in the area of anti-inflammatory treatment, the search for more
effective and safer compounds is a very active field of research. In this study
we investigated the anti-inflammatory effects of a known pseudopterane diterpene
(referred here as compound 1) isolated from the octocoral Pseudopterogorgia
acerosa on the tumor necrosis factor- alpha (TNF-alpha) and TLRs- induced
response in macrophages. Compound 1 inhibited the expression and secretion of the
inflammatory mediators TNF-alpha, interleukin (IL)-6, IL-1beta, nitric oxide
(NO), interferon gamma-induced protein 10 (IP-10), ciclooxygenase (COX)-2,
inducible nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1
(MCP-1) induced by LPS in primary murine macrophages. This effect was associated
with the inhibition of IkappaBalpha degradation and subsequent activation of
NFkappaB. Compound 1 also inhibited the expression of the co-stimulatory
molecules CD80 and CD86, which is a hallmark of macrophage activation and
consequent initiation of an adaptive immune response. The anti-inflammatory
effect was not exclusive to LPS because compound 1 also inhibited the response of
macrophages to TNF-alpha and TLR2 and TLR3 ligands. Taken together, these results
indicate that compound 1 is an anti-inflammatory molecule, which modulates a
variety of processes occurring in macrophage activation.
PMID- 24358332
TI - Brain development after neonatal intermittent hyperoxia-hypoxia in the rat
studied by longitudinal MRI and immunohistochemistry.
AB - BACKGROUND: Neonatal intermittent hyperoxia-hypoxia (IHH) is involved in the
pathogenesis of retinopathy of prematurity. Whether similar oxygen fluctuations
will create pathological changes in the grey and white matter of the brain is
unknown. METHODS: From birth until postnatal day 14 (P14), two litters (total n =
22) were reared in IHH: hyperoxia (50% O2) interrupted by three consecutive two
minute episodes of hypoxia (12% O2) every sixth hour. Controls (n = 8) were
reared in room-air (20.9% O2). Longitudinal MRI (Diffusion Tensor Imaging and T2
mapping) was performed on P14 and P28 and retinal and brain tissue were examined
for histopathological changes. Long-term neurodevelopment was assessed on P20 and
P27. RESULTS: Mean, radial and axial diffusivity were higher in white matter of
IHH versus controls at P14 (p < 0.04), while fractional anisotropy (FA) was lower
in the hippocampal fimbria and tended to be lower in corpus callosum (p = 0.08)
and external capsule (p = 0.05). White matter diffusivity in IHH was similar to
controls at P28. Higher cortical vessel density (p = 0.005) was observed at P14.
Cortical and thalamic T2-relaxation time and mean diffusivity were higher in the
IHH group at P14 (p <= 0.03), and albumin leakage was present at P28. Rats in the
IHH group ran for a longer time on a Rotarod than the control group (p <= 0.005).
Pups with lower bodyweight had more severe MRI alterations and albumin leakage.
CONCLUSION: IHH led to subtle reversible changes in brain white matter
diffusivity, grey matter water content and vascular density. However, alterations
in blood-brain barrier permeability may point to long-term effects. The changes
seen after IHH exposure were more severe in animals with lower bodyweight and
future studies should aim at exploring possible interactions between IHH and
growth restriction.
PMID- 24358333
TI - Community-based interventions to improve HPV vaccination coverage among 13- to 15
year-old females: measures implemented by local governments in Japan.
AB - The purpose of this study was to examine the effect of various community-based
interventions in support of HPV vaccination implemented by cities and towns
within Tochigi prefecture, Japan with a view to identifying useful indicators
which might guide future interventions to improve HPV vaccination coverage in the
prefecture. A postal questionnaire survey of all 27 local governments in Tochigi
Prefecture was conducted in December 2010. All 27 responded, and 22 provided the
exact numbers of the targeted and vaccinated populations of 13- to 15-year-old
girls from April to December 2010. The local governments also answered questions
on the type of interventions implemented including public subsidies, school-based
programs, direct mail, free tickets and recalls. Local governments that conducted
a school-based vaccination program reported 96.8% coverage for the 1(st) dose,
96.2% for the 2(nd) dose, and 91.2% for the 3(rd) dose. Those that provided
subsidies without school-based programs reported a wide range of vaccination
rates: 45.7%-95.0% for the 1(st) dose, 41.1%-93.7% for the 2(nd) dose and 3.1%
90.1% for the 3(rd) dose. Among this group, the combination of a free ticket,
direct mail and recall was most effective, with 95.0% coverage for the 1(st)
dose, 93.7% for the 2(nd) dose, and 90.1% for the 3(rd) dose. The governments
that did not offer a subsidy had the lowest vaccination coverage, with 0.8%-1.4%
for the 1(st) dose, 0.0%-0.8% for the 2(nd) dose, and 0.1%-0.1% for the 3(rd)
dose. The results of this survey indicate that school-based vaccinations and
public subsidies are the most effective method to improve HPV vaccination
coverage; however, the combination of a free ticket, direct mail, and recalls
with public subsidies are also important measures in increasing the vaccination
rate. These data may afford important indicators for the successful
implementation of future HPV vaccination programs.
PMID- 24358334
TI - Hydrokinetic turbine effects on fish swimming behaviour.
AB - Hydrokinetic turbines, targeting the kinetic energy of fast-flowing currents, are
under development with some turbines already deployed at ocean sites around the
world. It remains virtually unknown as to how these technologies affect fish, and
rotor collisions have been postulated as a major concern. In this study the
effects of a vertical axis hydrokinetic rotor with rotational speeds up to 70 rpm
were tested on the swimming patterns of naturally occurring fish in a subtropical
tidal channel. Fish movements were recorded with and without the rotor in place.
Results showed that no fish collided with the rotor and only a few specimens
passed through rotor blades. Overall, fish reduced their movements through the
area when the rotor was present. This deterrent effect on fish increased with
current speed. Fish that passed the rotor avoided the near-field, about 0.3 m
from the rotor for benthic reef fish. Large predatory fish were particularly
cautious of the rotor and never moved closer than 1.7 m in current speeds above
0.6 ms(-1). The effects of the rotor differed among taxa and feeding guilds and
it is suggested that fish boldness and body shape influenced responses. In
conclusion, the tested hydrokinetic turbine rotor proved non-hazardous to fish
during the investigated conditions. However, the results indicate that arrays
comprising multiple turbines may restrict fish movements, particularly for large
species, with possible effects on habitat connectivity if migration routes are
exploited. Arrays of the investigated turbine type and comparable systems should
therefore be designed with gaps of several metres width to allow large fish to
pass through. In combination with further research the insights from this study
can be used for guiding the design of hydrokinetic turbine arrays where needed,
so preventing ecological impacts.
PMID- 24358335
TI - Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma
tumors.
AB - The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen
species (ROS) and is mainly expressed in phagocytes. While the activity of the
NOX2 complex is essential for immunity against pathogens and protection against
autoimmunity, its role in the development of malignant tumors remains unclear. We
compared wild type and Ncf1 (m1J) mutated mice, which lack functional NOX2
complex, in four different tumor models. Ncf1 (m1J) mutated mice developed
significantly smaller tumors in two melanoma models in which B16 melanoma cells
expressing a hematopoietic growth factor FLT3L or luciferase reporter were used.
Ncf1 (m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC)
tumors, but the tumors that did develop, grew at a pace that was similar to the
wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP),
tumor growth was not affected. The lack of ROS-mediated protection against tumor
growth was associated with increased production of immunity-associated cytokines.
A significant increase in Th2 associated cytokines was observed in the LLC model.
Our present data show that ROS regulate rejection of the antigenic B16-luc and
LLC tumors, whereas the data do not support a role for ROS in growth of
intrinsically generated tumors.
PMID- 24358336
TI - Factors associated with quality of life among hemodialysis patients in Malaysia.
AB - Although hemodialysis treatment has greatly increased the life expectancy of end
stage renal disease patients, low quality of life among hemodialysis patients is
frequently reported. This cross-sectional study aimed to determine the
relationship between medical history, hemodialysis treatment and nutritional
status with the mental and physical components of quality of life in hemodialysis
patients. Respondents (n=90) were recruited from Hospital Kuala Lumpur and
dialysis centres of the National Kidney Foundation of Malaysia. Data obtained
included socio-demography, medical history, hemodialysis treatment and
nutritional status. Mental and physical quality of life were measured using the
Mental Composite Summary (MCS) and Physical Composite Summary (PCS) of the Short
Form Health Survey 36-items, a generic core of the Kidney Disease Quality of Life
Short Form. Two summary measures and total SF-36 was scored as 0-100, with a
higher score indicating better quality of life. Approximately 26 (30%) of
respondents achieved the body mass index (24 kg/m(2)) and more than 80% (n=77)
achieved serum albumin level (>35.0 mg/dL) recommended for hemodialysis patients.
The majority of respondents did not meet the energy (n=72, 80%) and protein
(n=68,75%) recommendations. The total score of SF-36 was 54.1 +/- 19.2, while the
score for the mental and physical components were 45.0 +/- 8.6 and 39.6 +/- 8.6,
respectively. Factors associated with a higher MCS score were absence of diabetes
mellitus (p=0.000) and lower serum calcium (p=0.004), while higher blood flow
(p=0.000), higher serum creatinine (p=0.000) and lower protein intake (p=0.006)
were associated with a higher PCS score. To improve the overall quality of life
of hemodialysis patients, a multidisciplinary intervention that includes medical,
dietetic and psychosocial strategies that address factors associated with mental
and physical quality of life are warranted to reduce further health complications
and to improve quality of life.
PMID- 24358337
TI - Systemic inflammation decreases pain threshold in humans in vivo.
AB - BACKGROUND: Hyperalgesia is a well recognized hallmark of disease. Pro
inflammatory cytokines have been suggested to be mainly responsible, but human
data are scarce. Changes in pain threshold during systemic inflammation evoked by
human endotoxemia, were evaluated with three quantitative sensory testing
methods. METHODS AND RESULTS: Pressure pain thresholds, electrical pain
thresholds and tolerance to the cold pressor test were measured before and 2
hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin
in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served
as controls. Endotoxemia led to a rise in body temperature and inflammatory
symptom scores and a rise in plasma TNF-alpha, IL-6, IL-10 and IL-1RA. During
endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced
with 20 +/- 4 % and 13 +/- 3 %, respectively. In controls only a minor decrease
in pressure pain thresholds (7 +/- 3 %) and no change in electrical pain
thresholds occurred. Endotoxin-treated subjects experienced more pain during the
cold pressor test, and fewer subjects were able to complete the cold pressor test
measurement, while in controls the cold pressor test results were not altered.
Peak levels and area under curves of each individual cytokine did not correlate
to a change in pain threshold measured by one of the applied quantitative sensory
testing techniques. CONCLUSIONS AND SIGNIFICANCE: In conclusion, this study shows
that systemic inflammation elicited by the administration of endotoxin to humans,
results in lowering of the pain threshold measured by 3 quantitative sensory
testing techniques. The current work provides additional evidence that systemic
inflammation is accompanied by changes in pain perception.
PMID- 24358338
TI - The utility of shallow RNA-Seq for documenting differential gene expression in
genes with high and low levels of expression.
AB - The sequencing depth necessary for documenting differential gene expression using
RNA-Seq has been little explored outside of model systems. In particular, the
depth required to analyze large-scale patterns of differential transcription
factor expression is not known. The goal of the present study is to explore the
effectiveness of shallow (relatively low read depth) RNA-Seq. We focus on two
tissues in the honey bee: the sting gland and the digestive tract. The sting
gland is an experimentally well-understood tissue that we use to benchmark the
utility of this approach. We use the digestive tract to test the results obtained
with the sting gland, and to conduct RNA-Seq between tissue types. Using a list
of experimentally verified genes conferring tissue-specific functions in the
sting gland, we show that relatively little read depth is necessary to identify
them. We argue that this result should be broadly applicable, since genes
important for tissue-specific functions often have robust expression patterns,
and because we obtained similar results in our analysis of the digestive tract.
Furthermore, we demonstrate that the differential expression of transcription
factors, which are transcribed at low levels compared to other genes, can
nevertheless often be determined using shallow RNA-Seq. Overall, we find over 150
differentially expressed transcription factors in our tissues at a read depth of
only 12 million. This work shows the utility of low-depth sequencing for
identifying genes important for tissue-specific functions. It also verifies the
often-held belief that transcription factors show low levels of expression, while
demonstrating that, in spite of this, they are frequently amenable to shallow RNA
Seq. Our findings should be of benefit to researchers using RNA-Seq in many
different biological systems.
PMID- 24358339
TI - Molecular mechanisms mediating a deficit in recall of fear extinction in adult
mice exposed to cocaine in utero.
AB - Prenatal cocaine exposure has been shown to alter cognitive processes of exposed
individuals, presumed to be a result of long-lasting molecular alterations in the
brain. In adult prenatal cocaine exposed (PCOC) mice we have identified a deficit
in recall of fear extinction, a behavior that is dependent on the medial
prefrontal cortex (mPFC) and the hippocampus. While we observed no change in the
constitutive expression of brain derived neurotrophic factor (BDNF) protein and
mRNA in the mPFC and hippocampus of adult PCOC mice, we observed blunted BDNF
signaling in the mPFC of adult PCOC mice after fear extinction compared to the
control animals. Specifically, during the consolidation phase of the extinction
memory, we observed a decrease in BDNF protein and it's phospho-TrkB receptor
expression. Interestingly, at this same time point there was a significant
increase in total Bdnf mRNA levels in the mPFC of PCOC mice as compared with
controls. In the Bdnf gene, we identified decreased constitutive binding of the
transcription factors, MeCP2 and P-CREB at the promoters of Bdnf exons I and IV
in the mPFC of PCOC mice, that unlike control mice remained unchanged when
measured during the behavior. Finally, bilateral infusion of recombinant BDNF
protein into the infralimbic subdivision of the mPFC during the consolidation
phase of the extinction memory rescued the behavioral deficit in PCOC mice. In
conclusion, these findings extend our knowledge of the neurobiologic impact of
prenatal cocaine exposure on the mPFC of mice, which may lead to improved
clinical recognition and treatment of exposed individuals.
PMID- 24358340
TI - Molecular and biochemical analyses of CbCel9A/Cel48A, a highly secreted multi
modular cellulase by Caldicellulosiruptor bescii during growth on crystalline
cellulose.
AB - During growth on crystalline cellulose, the thermophilic bacterium
Caldicellulosiruptor bescii secretes several cellulose-degrading enzymes. Among
these enzymes is CelA (CbCel9A/Cel48A), which is reported as the most highly
secreted cellulolytic enzyme in this bacterium. CbCel9A/Cel48A is a large multi
modular polypeptide, composed of an N-terminal catalytic glycoside hydrolase
family 9 (GH9) module and a C-terminal GH48 catalytic module that are separated
by a family 3c carbohydrate-binding module (CBM3c) and two identical CBM3bs. The
wild-type CbCel9A/Cel48A and its truncational mutants were expressed in Bacillus
megaterium and Escherichia coli, respectively. The wild-type polypeptide released
twice the amount of glucose equivalents from Avicel than its truncational mutant
that lacks the GH48 catalytic module. The truncational mutant harboring the GH9
module and the CBM3c was more thermostable than the wild-type protein, likely due
to its compact structure. The main hydrolytic activity was present in the GH9
catalytic module, while the truncational mutant containing the GH48 module and
the three CBMs was ineffective in degradation of either crystalline or amorphous
cellulose. Interestingly, the GH9 and/or GH48 catalytic modules containing the
CBM3bs form low-density particles during hydrolysis of crystalline cellulose.
Moreover, TM3 (GH9/CBM3c) and TM2 (GH48 with three CBM3 modules) synergistically
hydrolyze crystalline cellulose. Deletion of the CBM3bs or mutations that
compromised their binding activity suggested that these CBMs are important during
hydrolysis of crystalline cellulose. In agreement with this observation, seven of
nine genes in a C. bescii gene cluster predicted to encode cellulose-degrading
enzymes harbor CBM3bs. Based on our results, we hypothesize that C. bescii uses
the GH48 module and the CBM3bs in CbCel9A/Cel48A to destabilize certain regions
of crystalline cellulose for attack by the highly active GH9 module and other
endoglucanases produced by this hyperthermophilic bacterium.
PMID- 24358341
TI - ERK5 activation by Gq-coupled muscarinic receptors is independent of receptor
internalization and beta-arrestin recruitment.
AB - G-protein-coupled receptors (GPCRs) are known to activate both G protein- and
beta-arrestin-dependent signalling cascades. The initiation of mitogen-activated
protein kinase (MAPK) pathways is a key downstream event in the control of
cellular functions including proliferation, differentiation, migration and
apoptosis. Both G proteins and beta-arrestins have been reported to mediate
context-specific activation of ERK1/2, p38 and JNK MAPKs. Recently, the
activation of ERK5 MAPK by Gq-coupled receptors has been described to involve a
direct interaction between Galphaq and two novel effectors, PKCzeta and MEK5.
However, the possible contribution of beta-arrestin towards this pathway has not
yet been addressed. In the present work we sought to investigate the role of
receptor internalization processes and beta-arrestin recruitment in the
activation of ERK5 by Gq-coupled GPCRs. Our results show that ERK5 activation is
independent of M1 or M3 muscarinic receptor internalization. Furthermore, we
demonstrate that phosphorylation-deficient muscarinic M1 and M3 receptors are
still able to fully activate the ERK5 pathway, despite their reported inability
to recruit beta-arrestins. Indeed, the overexpression of Galphaq, but not that of
beta-arrestin1 or beta-arrestin2, was found to potently enhance ERK5 activation
by GPCRs, whereas silencing of beta-arrestin2 expression did not affect the
activation of this pathway. Finally, we show that a beta-arrestin-biased mutant
form of angiotensin II (SII; Sar1-Ile4-Ile8 AngII) failed to promote ERK5
phosphorylation in primary cardiac fibroblasts, as compared to the natural
ligand. Overall, this study shows that the activation of ERK5 MAPK by model Gq
coupled GPCRs does not depend on receptor internalization, beta-arrestin
recruitment or receptor phosphorylation but rather is dependent on Galphaq
signalling.
PMID- 24358342
TI - Salinomycin activates AMP-activated protein kinase-dependent autophagy in
cultured osteoblastoma cells: a negative regulator against cell apoptosis.
AB - BACKGROUND: The malignant osteoblastoma has poor prognosis, thus the search for
novel and more efficient chemo-agents against this disease is urgent. Salinomycin
induces broad anti-cancer effects both in vivo and in vitro, however, its role in
osteoblastoma is still not clear. KEY FINDINGS: Salinomycin induced both
apoptosis and autophagy in cultured U2OS and MG-63 osteoblastoma cells.
Inhibition of autophagy by 3-methyladenine (3-MA), or by RNA interference (RNAi)
of light chain 3B (LC3B), enhanced salinomycin-induced cytotoxicity and
apoptosis. Salinomycin induced a profound AMP-activated protein kinase (AMPK)
activation, which was required for autophagy induction. AMPK inhibition by
compound C, or by AMPKalpha RNAi prevented salinomycin-induced autophagy
activation, while facilitating cancer cell death and apoptosis. On the other
hand, the AMPK agonist AICAR promoted autophagy activation in U2OS cells.
Salinomycin-induced AMPK activation was dependent on reactive oxygen species
(ROS) production in osteoblastoma cells. Antioxidant n-acetyl cysteine (NAC)
significantly inhibited salinomycin-induced AMPK activation and autophagy
induction. CONCLUSIONS: Salinomycin activates AMPK-dependent autophagy in
osteoblastoma cells, which serves as a negative regulator against cell apoptosis.
AMPK-autophagy inhibition might be a novel strategy to sensitize salinomycin's
effect in cancer cells.
PMID- 24358343
TI - B cell responses to HIV antigen are a potent correlate of viremia in HIV-1
infection and improve with PD-1 blockade.
AB - Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of
both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell
dysfunction may partially explain the low frequency of broadly neutralizing
antibodies in HIV-infected individuals. To understand the extent of B cell
dysfunction during HIV infection, we assessed the level of B cell activation at
baseline and after stimulation with a variety of antigens. Increased levels of
viremia were associated with higher baseline expression of the activation marker
CD86 on B cells and with decreased ability of B cells to increase expression of
CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell
isolation experiments B cell responses to antigen were enhanced in the presence
of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD
1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B
cell responsiveness to HIV antigen, suggesting that inhibitory molecule
expression during HIV-1 infection may contribute to some of the observed B cell
defects. Our findings demonstrate that during chronic HIV infection, B cells are
activated and lose full capacity to respond to antigen, but suppression of
inhibitory pressures as well as a robust CD4+ T cell response may help preserve B
cell function.
PMID- 24358344
TI - Identification of cardiovascular risk components in urban Chinese with metabolic
syndrome and application to coronary heart disease prediction: a longitudinal
study.
AB - BACKGROUND: Metabolic syndrome (MetS) is proposed as a predictor for
cardiovascular disease (CVD). It involves the mechanisms of insulin resistance,
obesity, inflammation process of atherosclerosis, and their complex relationship
in the metabolic network. Therefore, more cardiovascular risk-related biomarkers
within this network should be considered as components of MetS in order to
improve the prediction of CVD. METHODS: Factor analysis was performed in 5311
(4574 males and 737 females) Han Chinese subjects with MetS to extract CVD
related factors with specific clinical significance from 16 biomarkers tested in
routine health check-up. Logistic regression model, based on an extreme case
control design with 445 coronary heart disease (CHD) patients and 890 controls,
was performed to evaluate the extracted factors used to identify CHD. Then, Cox
model, based on a cohort design with 1923 subjects followed up for 5 years, was
conducted to validate their predictive effects. Finally, a synthetic predictor
(SP) was created by weighting each factor with their risks for CHD to develop a
risk matrix to predicting CHD. RESULTS: Eight factors were obtained from both
males and females with a similar pattern. The AUC to classify CHD under the
extreme case-control suggested that SP might serve as a useful tool in
identifying CHD with 0.994 (95%CI 0.984-0.998) for males and 0.998 (95%CI 0.982
1.000) for females respectively. In the cohort study, the AUC to predict CHD was
0.871 (95%CI 0.851-0.889) for males and 0.899 (95%CI 0.873-0.921) for females,
highlighting that SP was a powerful predictor for CHD. The SP-based 5-year CHD
risk matrix provided as convenient tool for CHD risk appraisal. CONCLUSIONS:
Eight factors were extracted from sixteen biomarkers in subjects with MetS and
the SP adds to new insights into studies of prediction of CHD risk using data
from routine health check-up.
PMID- 24358345
TI - The complete mitochondrial genomes of two octopods Cistopus chinensis and
Cistopus taiwanicus: revealing the phylogenetic position of the genus Cistopus
within the order Octopoda.
AB - In the present study, we determined the complete mitochondrial DNA (mtDNA)
sequences of two species of Cistopus, namely C. chinensis and C. taiwanicus, and
conducted a comparative mt genome analysis across the class Cephalopoda. The
mtDNA length of C. chinensis and C. taiwanicus are 15706 and 15793 nucleotides
with an AT content of 76.21% and 76.5%, respectively. The sequence identity of
mtDNA between C. chinensis and C. taiwanicus was 88%, suggesting a close
relationship. Compared with C. taiwanicus and other octopods, C. chinensis
encoded two additional tRNA genes, showing a novel gene arrangement. In addition,
an unusual 23 poly (A) signal structure is found in the ATP8 coding region of C.
chinensis. The entire genome and each protein coding gene of the two Cistopus
species displayed notable levels of AT and GC skews. Based on sliding window
analysis among Octopodiformes, ND1 and DN5 were considered to be more reliable
molecular beacons. Phylogenetic analyses based on the 13 protein-coding genes
revealed that C. chinensis and C. taiwanicus form a monophyletic group with high
statistical support, consistent with previous studies based on morphological
characteristics. Our results also indicated that the phylogenetic position of the
genus Cistopus is closer to Octopus than to Amphioctopus and Callistoctopus. The
complete mtDNA sequence of C. chinensis and C. taiwanicus represent the first
whole mt genomes in the genus Cistopus. These novel mtDNA data will be important
in refining the phylogenetic relationships within Octopodiformes and enriching
the resource of markers for systematic, population genetic and evolutionary
biological studies of Cephalopoda.
PMID- 24358346
TI - Of travertine and time: otolith chemistry and microstructure detect provenance
and demography of endangered humpback chub in Grand Canyon, USA.
AB - We developed a geochemical atlas of the Colorado River in Grand Canyon and in its
tributary, the Little Colorado River, and used it to identify provenance and
habitat use by Federally Endangered humpback chub, Gila cypha. Carbon stable
isotope ratios (delta(13)C) discriminate best between the two rivers, but fine
scale analysis in otoliths requires rare, expensive instrumentation. We therefore
correlated other tracers (SrSr, Ba, and Se in ratio to Ca) to delta(13)C that are
easier to quantify in otoliths with other microchemical techniques. Although the
Little Colorado River's water chemistry varies with major storm events, at base
flow or near base flow (conditions occurring 84% of the time in our study) its
chemistry differs sufficiently from the mainstem to discriminate one from the
other. Additionally, when fish egress from the natal Little Colorado River to the
mainstem, they encounter cold water which causes the otolith daily growth
increments to decrease in size markedly. Combining otolith growth increment
analysis and microchemistry permitted estimation of size and age at first egress;
size at first birthday was also estimated. Emigrants < 1 year old averaged 51.2
+/- 4.4 (SE) days and 35.5 +/- 3.6 mm at egress; older fish that had recruited to
the population averaged 100 +/- 7.8 days old and 51.0 +/- 2.2 mm at egress,
suggesting that larger, older emigrants recruit better. Back-calculated size at
age 1 was unimodal and large (78.2 +/- 3.3 mm) in Little Colorado caught fish but
was bimodally distributed in Colorado mainstem caught fish (49.9 +/- 3.6 and 79
+/- 4.9 mm) suggesting that humpback chub can also rear in the mainstem. The
study demonstrates the coupled usage of the two rivers by this fish and
highlights the need to consider both rivers when making management decisions for
humpback chub recovery.
PMID- 24358347
TI - Adequate prenatal care reduces the risk of adverse pregnancy outcomes in women
with history of infertility: a nationwide population-based study.
AB - OBJECTIVES: To investigate the effects of various measures of prenatal care on
adverse pregnancy outcomes in women with a history of infertility. STUDY DESIGN:
A retrospective cohort study. METHODS: Data were derived by linking 2 large
nationwide population-based datasets, the National Health Insurance Research
Database and Taiwan Birth Certificate Registry. The study sample included 15,056
women with an infertility diagnosis and 60,224 randomly selected women without
infertility matched to the study sample by maternal age. A conditional logistic
regression analysis was performed for the analysis. RESULTS: Women diagnosed with
infertility respectively had 1.39 (95% CI, 1.06~1.83), 1.15 (95% CI, 1.08~1.24),
1.13 (95% CI, 1.08~1.18), and 1.08 (95% CI, 1.05~1.12) higher odds of having very
low birth weight (VLBW) babies, preterm births, labor complications, and cesarean
sections (CSs) compared to women without infertility. Inadequate numbers of total
and major prenatal visits and late initiation of prenatal care increased the
risks of adverse pregnancy outcomes in women with infertility, especially the
risk of a VLBW baby. However, no significant associations were found for the
risks of adverse birth outcomes in infertile women with adequate prenatal care
compared to fertile women with adequate care. CONCLUSIONS: Study findings suggest
that adequate prenatal care can reduce the risk of adverse pregnancy outcomes in
women with infertility.
PMID- 24358348
TI - Resting state FMRI reveals diminished functional connectivity in a mouse model of
amyloidosis.
AB - INTRODUCTION: Functional connectivity (FC) studies have gained immense popularity
in the evaluation of several neurological disorders, such as Alzheimer's disease
(AD). AD is a complex disorder, characterised by several pathological features.
The problem with FC studies in patients is that it is not straightforward to
focus on a specific aspect of pathology. In the current study, resting state
functional magnetic resonance imaging (rsfMRI) is applied in a mouse model of
amyloidosis to assess the effects of amyloid pathology on FC in the mouse brain.
METHODS: Nine APP/PS1 transgenic and nine wild-type mice (average age 18.9
months) were imaged on a 7T MRI system. The mice were anesthetized with
medetomidine and rsfMRI data were acquired using a gradient echo EPI sequence.
The data were analysed using a whole brain seed correlation analysis and
interhemispheric FC was evaluated using a pairwise seed analysis. Qualitative
histological analyses were performed to assess amyloid pathology, inflammation
and synaptic deficits. RESULTS: The whole brain seed analysis revealed an overall
decrease in FC in the brains of transgenic mice compared to wild-type mice. The
results showed that interhemispheric FC was relatively preserved in the motor
cortex of the transgenic mice, but decreased in the somatosensory cortex and the
hippocampus when compared to the wild-type mice. The pairwise seed analysis
confirmed these results. Histological analyses confirmed the presence of amyloid
pathology, inflammation and synaptic deficits in the transgenic mice.
CONCLUSIONS: In the current study, rsfMRI demonstrated decreased FC in APP/PS1
transgenic mice compared to wild-type mice in several brain regions. The APP/PS1
transgenic mice had advanced amyloid pathology across the brain, as well as
inflammation and synaptic deficits surrounding the amyloid plaques. Future
studies should longitudinally evaluate APP/PS1 transgenic mice and correlate the
rsfMRI findings to specific stages of amyloid pathology.
PMID- 24358349
TI - Highly efficient generation of GGTA1 biallelic knockout inbred mini-pigs with
TALENs.
AB - Inbred mini-pigs are ideal organ donors for future human xenotransplantations
because of their clear genetic background, high homozygosity, and high inbreeding
endurance. In this study, we chose fibroblast cells from a highly inbred pig line
called Banna mini-pig inbred line (BMI) as donor nuclei for nuclear transfer,
combining with transcription activator-like effector nucleases (TALENs) and
successfully generated alpha-1,3-galactosyltransferase (GGTA1) gene biallelic
knockout (KO) pigs. To validate the efficiency of TALEN vectors, in vitro
transcribed TALEN mRNAs were microinjected into one-cell stage
parthenogenetically activated porcine embryos. The efficiency of indel mutations
at the GGTA1-targeting loci was as high as 73.1% (19/26) among the
parthenogenetic blastocysts. TALENs were co-transfected into porcine fetal
fibroblasts of BMI with a plasmid containing neomycin gene. The targeting
efficiency reached 89.5% (187/209) among the survived cell clones after a 10 d
selection. More remarkably 27.8% (58/209) of colonies were biallelic KO. Five
fibroblast cell lines with biallelic KO were chosen as nuclear donors for somatic
cell nuclear transfer (SCNT). Three miniature piglets with biallelic mutations of
the GGTA1 gene were achieved. Gal epitopes on the surface of cells from all the
three biallelic KO piglets were completely absent. The fibroblasts from the GGTA1
null piglets were more resistant to lysis by pooled complement-preserved normal
human serum than those from wild-type pigs. These results indicate that a
combination of TALENs technology with SCNT can generate biallelic KO pigs
directly with high efficiency. The GGTA1 null piglets with inbred features
created in this study can provide a new organ source for xenotransplantation
research.
PMID- 24358350
TI - Intensified tuberculosis case finding among malnourished children in nutritional
rehabilitation centres of Karnataka, India: missed opportunities.
AB - BACKGROUND: Severe acute malnutrition (SAM) is the most serious form of
malnutrition affecting children under-five and is associated with many infectious
diseases including Tuberculosis (TB). In India, nutritional rehabilitation
centres (NRCs) have been recently established for the management of SAM including
TB. The National TB Programme (NTP) in India has introduced a revised algorithm
for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these
guidelines in diagnosing TB among SAM children. METHODS: A cross-sectional study
involving review of records of all SAM children identified by health workers
during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of
Karnataka, India. RESULTS: Of 1927 identified SAM children, 1632 (85%) reached
NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB.
Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not
evaluated as per algorithm, tuberculin skin test alone was conducted in 307
(41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%).
The yield of TB was higher among children evaluated as per algorithm (4%) as
compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several
operational challenges including non-availability of a full-time paediatrician,
non-functioning X-ray machine due to frequent power cuts, use of tuberculin with
suboptimal strength and difficulties in adhering to a complex diagnostic
algorithm were observed. CONCLUSION: This study showed that TB screening in NRCs
was sub-optimal in Karnataka. Some children did not reach the NRC, while many of
those who did were either not or sub-optimally evaluated for TB. This study
pointed to a number of operational issues that need to be addressed if this
collaborative strategy is to identify more TB cases amongst malnourished children
in India.
PMID- 24358351
TI - Prevalence and clinical characteristics associated with pulmonary hypertension in
African-Americans.
AB - BACKGROUND: Pulmonary hypertension (PH) is associated with increased mortality
and morbidity. It is frequently associated with cardiopulmonary diseases that are
prevalent in African Americans (AAs). However, the prevalence or determinants of
PH in the AA population is not known. METHODS: We conducted a cross-sectional
study to estimate the prevalence of PH (defined as trans-tricuspid gradient >= 35
mm Hg) and associated clinical characteristics in AAs using the Jackson Heart
Study cohort (n=3,282) who underwent echocardiography and had a measurable trans
tricuspid regurgitant jet. Echocardiography is frequently used for screening for
PH despite its limitations in estimating accurate PA systolic pressures. Overall
and age-adjusted gender-specific prevalence were estimated and modified Poisson
regression was used to identify independent clinical, spirometric, and
echocardiographic characteristics associated with PH. RESULTS: The mean age of
the study population was 56.1 +/- 12.6 years with 67.5% female. The prevalence of
PH was 6.8%, with higher prevalence in female AAs (age-adjusted prevalence: Men
4.9%, 95% CI 3.6-6.2%; Women 7.7%, 95% CI 6.6-8.8%). Pulmonary hypertension
prevalence increased with age (Prevalence Ratio: 10.0, 95%CI 4.0-25.1, >65 versus
<45 years old), presence of obesity, higher pulse pressure, diabetes, obstructive
or restrictive spirometry pattern, and severe left heart valvular disease. Also,
PH was significantly associated with left atrial size and left ventricular
ejection fraction. CONCLUSIONS: Pulmonary hypertension is prevalent in AAs, more
in women than in men. The identified cardiopulmonary risk factors that increase
the prevalence of PH may assist in diagnosis and management of these at-risk
subjects in the AA population.
PMID- 24358352
TI - Mechanisms and consequences of developmental acceleration in tadpoles responding
to pond drying.
AB - Many amphibian species exploit temporary or even ephemeral aquatic habitats for
reproduction by maximising larval growth under benign conditions but accelerating
development to rapidly undergo metamorphosis when at risk of desiccation from
pond drying. Here we determine mechanisms enabling developmental acceleration in
response to decreased water levels in western spadefoot toad tadpoles (Pelobates
cultripes), a species with long larval periods and large size at metamorphosis
but with a high degree of developmental plasticity. We found that P. cultripes
tadpoles can shorten their larval period by an average of 30% in response to
reduced water levels. We show that such developmental acceleration was achieved
via increased endogenous levels of corticosterone and thyroid hormone, which act
synergistically to achieve metamorphosis, and also by increased expression of the
thyroid hormone receptor TRBeta, which increases tissue sensitivity and
responsivity to thyroid hormone. However, developmental acceleration had
morphological and physiological consequences. In addition to resulting in smaller
juveniles with proportionately shorter limbs, tadpoles exposed to decreased water
levels incurred oxidative stress, indicated by increased activity of the
antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase.
Such increases were apparently sufficient to neutralise the oxidative damage
caused by presumed increased metabolic activity. Thus, developmental acceleration
allows spadefoot toad tadpoles to evade drying ponds, but it comes at the expense
of reduced size at metamorphosis and increased oxidative stress.
PMID- 24358353
TI - Soluble CD40 ligand stimulates the pro-angiogenic function of peripheral blood
angiogenic outgrowth cells via increased release of matrix metalloproteinase-9.
AB - The role of endothelial progenitor cells in vascular repair is related to their
incorporation at sites of vascular lesions, differentiation into endothelial
cells, and release of various angiogenic factors specifically by a subset of
early outgrowth endothelial progenitor cells (EOCs). It has been shown that
patients suffering from cardiovascular disease exhibit increased levels of
circulating and soluble CD40 ligand (sCD40L), which may influence the function of
EOCs. We have previously shown that the inflammatory receptor CD40 is expressed
on EOCs and its ligation with sCD40L impairs the anti-platelet function of EOCs.
In the present study, we aimed at investigating the effect of sCD40L on the
function of EOCs in endothelial repair. Human peripheral blood mononuclear cell
derived EOCs express CD40 and its adaptor proteins, the tumor necrosis factor
receptor-associated factors; TRAF1, TRAF2 and TRAF3. Stimulation of EOCs with
sCD40L increased the expression of TRAF1, binding of TRAF2 to CD40 and
phosphorylation of p38 mitogen activated protein kinase (MAPK). In an in vitro
wound healing assay, stimulation of EOCs with sCD40L increased the release of
matrix metalloproteinase 9 (MMP-9) in a concentration-dependent manner and
significantly enhanced the angiogenic potential of cultured human umbilical vein
endothelial cells (HUVECs). Inhibition of p38 MAPK reversed sCD40L-induced MMP-9
release by EOCs, whereas inhibition of MMP-9 reversed their pro-angiogenic effect
on HUVECs. This study reveals the existence of a CD40L/CD40/TRAF axis in EOCs and
shows that sCD40L increases the pro-angiogenic function of EOCs on cultured
HUVECs by inducing a significant increase in MMP-9 release via, at least, the p38
MAPK signaling pathway.
PMID- 24358354
TI - Co-expression of SERCA isoforms, phospholamban and sarcolipin in human skeletal
muscle fibers.
AB - Sarcolipin (SLN) and phospholamban (PLN) inhibit the activity of
sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs) by reducing their apparent
affinity for Ca(2+). A ternary complex between SLN, PLN, and SERCAs results in
super-inhibition of SERCA activity. Analysis of skeletal muscle homogenate has
limited our current understanding of whether SLN and PLN regulate SERCA1a,
SERCA2a, or both in skeletal muscle and whether SLN and PLN are co-expressed in
skeletal muscle fibers. Biopsies from human vastus lateralis were analyzed
through single fiber Western blotting and immunohisto/fluorescence staining to
circumvent this limitation. With a newly generated SLN antibody, we report for
the first time that SLN protein is present in human skeletal muscle. Addition of
the SLN antibody (50 ug) to vastus lateralis homogenates increased the apparent
Ca(2+) affinity of SERCA (K Ca, pCa units) (-Ab, 5.85 +/- 0.02 vs. +Ab, 5.95 +/-
0.02) and maximal SERCA activity (MUmol/g protein/min) (-Ab, 122 +/- 6.4 vs. +Ab,
159 +/- 11) demonstrating a functional interaction between SLN and SERCAs in
human vastus lateralis. Specifically, our results suggest that although SLN and
PLN may preferentially regulate SERCA1a, and SERCA2a, respectively,
physiologically they both may regulate either SERCA isoform. Furthermore, we show
that SLN and PLN co-immunoprecipitate in human vastus lateralis homogenate and
are simultaneously expressed in 81% of the fibers analyzed with Western blotting
which implies that super-inhibition of SERCA may exist in human skeletal muscle.
Finally, we demonstrate unequivocally that mouse soleus contains PLN protein
suggesting that super-inhibition of SERCA may also be important physiologically
in rodent skeletal muscle.
PMID- 24358355
TI - Blue-violet laser modification of titania treated titanium: antibacterial and
osteo-inductive effects.
AB - BACKGROUND: Many studies on surface modifications of titanium have been performed
in an attempt to accelerate osseointegration. Recently, anatase titanium dioxide
has been found to act as a photocatalyst that expresses antibiotic properties and
exhibits hydrophilicity after ultraviolet exposure. A blue-violet semiconductor
laser (BV-LD) has been developed as near-ultraviolet light. The purpose of this
study was to investigate the effects of exposure to this BV-LD on surface
modifications of titanium with the goal of enhancing osteoconductive and
antibacterial properties. METHODS: The surfaces of pure commercial titanium were
polished with #800 waterproof polishing papers and were treated with anatase
titania solution. Specimens were exposed using BV-LD (lambda = 405 nm) or an
ultraviolet light-emitting diode (UV-LED, lambda = 365 nm) at 6 mW/cm(2) for 3 h.
The surface modification was evaluated physically and biologically using the
following parameters or tests: surface roughness, surface temperature during
exposure, X-ray diffraction (XRD) analysis, contact angle, methylene blue
degradation tests, adherence of Porphyromonas gingivalis, osteoblast and
fibroblast proliferation, and histological examination after implantation in
rats. RESULTS: No significant changes were found in the surface roughness or XRD
profiles after exposure. BV-LD exposure did not raise the surface temperature of
titanium. The contact angle was significantly decreased, and methylene blue was
significantly degraded. The number of attached P. gingivalis organisms was
significantly reduced after BV-LD exposure compared to that in the no exposure
group. New bone was observed around exposed specimens in the histological
evaluation, and both the bone-to-specimen contact ratio and the new bone area
increased significantly in exposed groups. CONCLUSIONS: This study suggested that
exposure of titanium to BV-LD can enhance the osteoconductivity of the titanium
surface and induce antibacterial properties, similar to the properties observed
following exposure to UV-LED.
PMID- 24358356
TI - The complete maternally and paternally inherited mitochondrial genomes of the
endangered freshwater mussel Solenaia carinatus (Bivalvia: Unionidae) and
implications for Unionidae taxonomy.
AB - Doubly uniparental inheritance (DUI) is an exception to the typical maternal
inheritance of mitochondrial (mt) DNA in Metazoa, and found only in some
bivalves. In species with DUI, there are two highly divergent gender-associated
mt genomes: maternal (F) and paternal (M), which transmit independently and show
different tissue localization. Solenaia carinatus is an endangered freshwater
mussel species exclusive to Poyang Lake basin, China. Anthropogenic events in the
watershed greatly threaten the survival of this species. Nevertheless, the
taxonomy of S. carinatus based on shell morphology is confusing, and the
subfamilial placement of the genus Solenaia remains unclear. In order to clarify
the taxonomic status and discuss the phylogenetic implications of family
Unionidae, the entire F and M mt genomes of S. carinatus were sequenced and
compared with the mt genomes of diverse freshwater mussel species. The complete F
and M mt genomes of S. carinatus are 16716 bp and 17102 bp in size, respectively.
The F and M mt genomes of S. carinatus diverge by about 40% in nucleotide
sequence and 48% in amino acid sequence. Compared to F counterparts, the M genome
shows a more compact structure. Different gene arrangements are found in these
two gender-associated mt genomes. Among these, the F genome cox2-rrnS gene order
is considered to be a genome-level synapomorphy for female lineage of the
subfamily Gonideinae. From maternal and paternal mtDNA perspectives, the
phylogenetic analyses of Unionoida indicate that S. carinatus belongs to
Gonideinae. The F and M clades in freshwater mussels are reciprocal monophyly.
The phylogenetic trees advocate the classification of sampled Unionidae species
into four subfamilies: Gonideinae, Ambleminae, Anodontinae, and Unioninae, which
is supported by the morphological characteristics of glochidia.
PMID- 24358358
TI - Pathway evidence of how musical perception predicts word-level reading ability in
children with reading difficulties.
AB - OBJECTIVE: To investigate whether specific domains of musical perception
(temporal and melodic domains) predict the word-level reading skills of eight- to
ten-year-old children (n = 235) with reading difficulties, normal quotient of
intelligence, and no previous exposure to music education classes. METHOD: A
general-specific solution of the Montreal Battery of Evaluation of Amusia (MBEA),
which underlies a musical perception construct and is constituted by three latent
factors (the general, temporal, and the melodic domain), was regressed on word
level reading skills (rate of correct isolated words/non-words read per minute).
RESULTS: General and melodic latent domains predicted word-level reading skills.
PMID- 24358357
TI - Requirement of NOX2 expression in both retina and bone marrow for diabetes
induced retinal vascular injury.
AB - OBJECTIVE: Diabetic retinopathy, a major cause of blindness, is characterized by
increased expression of vascular endothelial growth factor (VEGF), leukocyte
attachment to the vessel walls and increased vascular permeability. Previous work
has shown that reactive oxygen species (ROS) produced by the superoxide
generating enzyme NOX2/NADPH oxidase play a crucial role in the vascular
pathology. The aim of this work was to identify the cellular sources of the
damaging NOX2 activity by studies using bone marrow chimera mice. METHODS: Bone
marrow cells were collected from the femurs and tibias of wild type and NOX2
deficient (NOX2(-/-)) donor mice and injected intravenously into lethally
irradiated NOX2(-/-) and wild type recipients. Following recovery from radiation,
mice were rendered diabetic by streptozotocin injections. The following groups of
bone marrow chimeras were studied: non-diabetic WT -> WT, diabetic WT -> WT,
diabetic WT -> NOX2(-/-), diabetic NOX2(-/-) -> WT. After 4 weeks of diabetes,
early signs of retinopathy were examined by measuring ROS, expression of VEGF and
ICAM-1, leukocyte attachment to the vessel wall and vascular permeability.
RESULTS: The retinas of the diabetic WT -> WT chimeras showed significant
increases in ROS as compared with the non-diabetic chimeras. These diabetes
induced alterations were correlated with increases in expression of VEGF and ICAM
1, leukocyte adhesion and vascular permeability. Each of these diabetes-induced
alterations were significantly attenuated in the diabetic WT -> NOX2(-/-) and
NOX2(-/-) -> WT chimera groups (p<0.05). CONCLUSION: NOX2-generated ROS produced
by both bone marrow-derived cells and resident retinal cells contribute
importantly to retinal vascular injury in the diabetic retina. Targeting NOX2 in
bone marrow and/or retinal cells may represent a novel therapeutic strategy for
the treatment/prevention of vascular injury in the diabetic retina.
PMID- 24358359
TI - Plant traits demonstrate that temperate and tropical giant eucalypt forests are
ecologically convergent with rainforest not savanna.
AB - Ecological theory differentiates rainforest and open vegetation in many regions
as functionally divergent alternative stable states with transitional (ecotonal)
vegetation between the two forming transient unstable states. This transitional
vegetation is of considerable significance, not only as a test case for theories
of vegetation dynamics, but also because this type of vegetation is of major
economic importance, and is home to a suite of species of conservation
significance, including the world's tallest flowering plants. We therefore
created predictions of patterns in plant functional traits that would test the
alternative stable states model of these systems. We measured functional traits
of 128 trees and shrubs across tropical and temperate rainforest - open
vegetation transitions in Australia, with giant eucalypt forests situated between
these vegetation types. We analysed a set of functional traits: leaf carbon
isotopes, leaf area, leaf mass per area, leaf slenderness, wood density, maximum
height and bark thickness, using univariate and multivariate methods. For most
traits, giant eucalypt forest was similar to rainforest, while rainforest,
particularly tropical rainforest, was significantly different from the open
vegetation. In multivariate analyses, tropical and temperate rainforest diverged
functionally, and both segregated from open vegetation. Furthermore, the giant
eucalypt forests overlapped in function with their respective rainforests. The
two types of giant eucalypt forests also exhibited greater overall functional
similarity to each other than to any of the open vegetation types. We conclude
that tropical and temperate giant eucalypt forests are ecologically and
functionally convergent. The lack of clear functional differentiation from
rainforest suggests that giant eucalypt forests are unstable states within the
basin of attraction of rainforest. Our results have important implications for
giant eucalypt forest management.
PMID- 24358360
TI - Transmission of an oxygen availability signal at the Salmonella enterica serovar
Typhimurium fis promoter.
AB - The nucleoid-associated protein FIS is a global regulator of gene expression and
chromosome structure in Escherichia coli and Salmonella enterica. Despite the
importance of FIS for infection and intracellular invasion, very little is known
about the regulation of S. enterica fis expression. Under standard laboratory
growth conditions, fis is highly expressed during rapid growth but is then
silenced as growth slows. However, if cells are cultured in non-aerated
conditions, fis expression is sustained during stationary phase. This led us to
test whether the redox-sensing transcription factors ArcA and FNR regulate S.
enterica fis. Deletion of FNR had no detectable effect, whereas deletion of ArcA
had the unexpected effect of further elevating fis expression in stationary
phase. ArcA required RpoS for induction of fis expression, suggesting that ArcA
indirectly affects fis expression. Other putative regulators were found to play
diverse roles: FIS acted directly as an auto-repressor (as expected), whereas CRP
had little direct effect on fis expression. Deleting regions of the fis promoter
led to the discovery of a novel anaerobically-induced transcription start site
(Pfis-2) upstream of the primary transcription start site (Pfis-1). Promoter
truncation also revealed that the shortest functional fis promoter was incapable
of sustained expression. Moreover, fis expression was observed to correlate
directly with DNA supercoiling in non-aerated conditions. Thus, the full-length
S. enterica fis promoter region may act as a topological switch that is sensitive
to stress-induced duplex destabilisation and up-regulates expression in non
aerated conditions.
PMID- 24358361
TI - Identification of cytotoxic T lymphocyte epitopes on swine viruses: multi-epitope
design for universal T cell vaccine.
AB - Classical swine fever (CSF), foot-and-mouth disease (FMD) and porcine
reproductive and respiratory syndrome (PRRS) are the primary diseases affecting
the pig industry globally. Vaccine induced CD8(+) T cell-mediated immune response
might be long-lived and cross-serotype and thus deserve further attention.
Although large panels of synthetic overlapping peptides spanning the entire
length of the polyproteins of a virus facilitate the detection of cytotoxic T
lymphocyte (CTL) epitopes, it is an exceedingly costly and cumbersome approach.
Alternatively, computational predictions have been proven to be of satisfactory
accuracy and are easily performed. Such a method enables the systematic
identification of genome-wide CTL epitopes by incorporating epitope prediction
tools in analyzing large numbers of viral sequences. In this study, we have
implemented an integrated bioinformatics pipeline for the identification of CTL
epitopes of swine viruses including the CSF virus (CSFV), FMD virus (FMDV) and
PRRS virus (PRRSV) and assembled these epitopes on a web resource to facilitate
vaccine design. Identification of epitopes for cross protections to different
subtypes of virus are also reported in this study and may be useful for the
development of a universal vaccine against such viral infections among the swine
population. The CTL epitopes identified in this study have been evaluated in
silico and possibly provide more and wider protection in compared to traditional
single-reference vaccine design. The web resource is free and open to all users
through http://sb.nhri.org.tw/ICES.
PMID- 24358362
TI - Enrichment and training improve cognition in rats with cortical malformations.
AB - Children with malformations of cortical development (MCD) frequently have
associated cognitive impairments which reduce quality of life. We hypothesized
that cognitive deficits associated with MCD can be improved with environmental
manipulation or additional training. The E17 methylazoxymethanol acetate (MAM)
exposure model bears many anatomical hallmarks seen in human MCDs as well as
similar behavioral and cognitive deficits. We divided control and MAM exposed
Sprague-Dawley rats into enriched and non-enriched groups and tested performance
in the Morris water maze. Another group similarly divided underwent sociability
testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post
enrichment. A third group of control and MAM rats without enrichment were trained
until they reached criterion on the place avoidance task. MAM rats had impaired
performance on spatial tasks and enrichment improved performance of both control
and MAM animals. Although MAM rats did not have a deficit in sociability they
showed similar improvement with enrichment as controls. MRI revealed a whole
brain volume decrease with MAM exposure, and an increase in both MAM and control
enriched volumes in comparison to non-enriched animals. In the place avoidance
task, MAM rats required approximately 3 times as long to reach criterion as
control animals, but with additional training were able to reach control
performance. Environmental manipulation and additional training can improve
cognition in a rodent MCD model. We therefore suggest that patients with MCD may
benefit from appropriate alterations in educational strategies, social
interaction and environment. These factors should be considered in therapeutic
strategies.
PMID- 24358363
TI - Genetic patterns in European geometrid moths revealed by the Barcode Index Number
(BIN) system.
AB - BACKGROUND: The geometrid moths of Europe are one of the best investigated insect
groups in traditional taxonomy making them an ideal model group to test the
accuracy of the Barcode Index Number (BIN) system of BOLD (Barcode of Life
Datasystems), a method that supports automated, rapid species delineation and
identification. METHODOLOGY/PRINCIPAL FINDINGS: This study provides a DNA barcode
library for 219 of the 249 European geometrid moth species (88%) in five selected
subfamilies. The data set includes COI sequences for 2130 specimens. Most species
(93%) were found to possess diagnostic barcode sequences at the European level
while only three species pairs (3%) were genetically indistinguishable in areas
of sympatry. As a consequence, 97% of the European species we examined were
unequivocally discriminated by barcodes within their natural areas of
distribution. We found a 1:1 correspondence between BINs and traditionally
recognized species for 67% of these species. Another 17% of the species (15
pairs, three triads) shared BINs, while specimens from the remaining species
(18%) were divided among two or more BINs. Five of these species are mixtures,
both sharing and splitting BINs. For 82% of the species with two or more BINs,
the genetic splits involved allopatric populations, many of which have previously
been hypothesized to represent distinct species or subspecies.
CONCLUSIONS/SIGNIFICANCE: This study confirms the effectiveness of DNA barcoding
as a tool for species identification and illustrates the potential of the BIN
system to characterize formal genetic units independently of an existing
classification. This suggests the system can be used to efficiently assess the
biodiversity of large, poorly known assemblages of organisms. For the moths
examined in this study, cases of discordance between traditionally recognized
species and BINs arose from several causes including overlooked species,
synonymy, and cases where DNA barcodes revealed regional variation of uncertain
taxonomic significance.
PMID- 24358364
TI - Intestinal intraepithelial lymphocyte-enterocyte crosstalk regulates production
of bactericidal angiogenin 4 by Paneth cells upon microbial challenge.
AB - Antimicrobial proteins influence intestinal microbial ecology and limit
proliferation of pathogens, yet the regulation of their expression has only been
partially elucidated. Here, we have identified a putative pathway involving
epithelial cells and intestinal intraepithelial lymphocytes (iIELs) that leads to
antimicrobial protein (AMP) production by Paneth cells. Mice lacking gammadelta
iIELs (TCRdelta(-/-)) express significantly reduced levels of the AMP angiogenin
4 (Ang4). These mice were also unable to up-regulate Ang4 production following
oral challenge by Salmonella, leading to higher levels of mucosal invasion
compared to their wild type counterparts during the first 2 hours post-challenge.
The transfer of gammadelta iIELs from wild type (WT) mice to TCRdelta(-/-) mice
restored Ang4 production and Salmonella invasion levels were reduced to those
obtained in WT mice. The ability to restore Ang4 production in TCRdelta(-/-) mice
was shown to be restricted to gammadelta iIELs expressing Vgamma7-encoded TCRs.
Using a novel intestinal crypt co-culture system we identified a putative pathway
of Ang4 production initiated by exposure to Salmonella, intestinal commensals or
microbial antigens that induced intestinal epithelial cells to produce cytokines
including IL-23 in a TLR-mediated manner. Exposure of TCR-Vgamma7(+) gammadelta
iIELs to IL-23 promoted IL-22 production, which triggered Paneth cells to secrete
Ang4. These findings identify a novel role for gammadelta iIELs in mucosal
defence through sensing immediate epithelial cell cytokine responses and
influencing AMP production. This in turn can contribute to the maintenance of
intestinal microbial homeostasis and epithelial barrier function, and limit
pathogen invasion.
PMID- 24358365
TI - Environmental complexity and biodiversity: the multi-layered evolutionary history
of a log-dwelling velvet worm in Montane Temperate Australia.
AB - Phylogeographic studies provide a framework for understanding the importance of
intrinsic versus extrinsic factors in shaping patterns of biodiversity through
identifying past and present microevolutionary processes that contributed to
lineage divergence. Here we investigate population structure and diversity of the
Onychophoran (velvet worm) Euperipatoides rowelli in southeastern Australian
montane forests that were not subject to Pleistocene glaciations, and thus likely
retained more forest cover than systems under glaciation. Over a ~100 km transect
of structurally-connected forest, we found marked nuclear and mitochondrial (mt)
DNA genetic structuring, with spatially-localised groups. Patterns from mtDNA and
nuclear data broadly corresponded with previously defined geographic regions,
consistent with repeated isolation in refuges during Pleistocene climatic
cycling. Nevertheless, some E. rowelli genetic contact zones were displaced
relative to hypothesized influential landscape structures, implying more recent
processes overlying impacts of past environmental history. Major impacts at
different timescales were seen in the phylogenetic relationships among mtDNA
sequences, which matched geographic relationships and nuclear data only at recent
timescales, indicating historical gene flow and/or incomplete lineage sorting.
Five major E. rowelli phylogeographic groups were identified, showing substantial
but incomplete reproductive isolation despite continuous habitat. Regional
distinctiveness, in the face of lineages abutting within forest habitat, could
indicate pre- and/or postzygotic gene flow limitation. A potentially functional
phenotypic character, colour pattern variation, reflected the geographic patterns
in the molecular data. Spatial-genetic patterns broadly match those in previously
studied, co-occurring low-mobility organisms, despite a variety of life
histories. We suggest that for E. rowelli, the complex topography and history of
the region has led to interplay among limited dispersal ability, historical
responses to environmental change, local adaptation, and some resistance to free
admixture at geographic secondary contact, leading to strong genetic structuring
at fine spatial scale.
PMID- 24358366
TI - Phenylthiophenecarboxamide antagonists of the olfactory receptor co-receptor
subunit from a mosquito.
AB - Insects detect environmental chemicals using chemosensory receptors, such as the
ORs, a family of odorant-gated ion channels. Insect ORs are multimeric complexes
of unknown stoichiometry, formed by a common subunit (the odorant receptor co
receptor subunit, Orco) and one of many variable subunits that confer odorant
specificity. The recent discovery of Orco directed ligands, including both
agonists and antagonists, suggests Orco as a promising target for chemical
control of insects. In addition to competitively inhibiting OR activation by Orco
agonists, several Orco antagonists have been shown to act through a non
competitive mechanism to inhibit OR activation by odorants. We previously
identified a series of Orco antagonists, including N-(4-ethylphenyl)-2
thiophenecarboxamide (OX1a, previously referred to as OLC20). Here, we explore
the chemical space around the OX1a structure to identify more potent Orco
antagonists. Cqui?Orco+Cqui?Or21, an OR from Culex quinquefasciatus (the Southern
House Mosquito) that responds to 3-methylindole (skatole) and is thought to
mediate oviposition behavior, was expressed in Xenopus oocytes and receptor
function assayed by two-electrode voltage clamp electrophysiology. 22 structural
analogs of OX1a were screened for antagonism of OR activation by an Orco agonist.
By varying the moieties decorating the phenyl and thiophene rings, and altering
the distance between the rings, we were able to identify antagonists with
improved potency. Detailed examination of three of these compounds (N-mesityl-2
thiophenecarboxamide, N-(4-methylbenzyl)-2-thiophenecarboxamide and N-(2
ethylphenyl)-3-(2-thienyl)-2-propenamide) demonstrated competitive inhibition of
receptor activation by an Orco agonist and non-competitive inhibition of receptor
activation by an odorant. The ability to inhibit OR activation by odorants may be
a general property of this class of Orco antagonist, suggesting that odorant
mediated behaviors can be manipulated through Orco antagonism. The high
conservation of Orco across insect species and previous demonstrations that
various Orco ligands are active at ORs derived from several different insect
orders suggests that Orco antagonists may have broad applicability.
PMID- 24358367
TI - Nicotine increases cerebellar activity during finger tapping.
AB - Nicotine improves performance on several cognitive and sensorimotor tasks. The
neuronal mechanisms associated with these changes in performance are, however,
largely unknown. Functional magnetic resonance imaging (fMRI) was used to examine
the effect of nicotine on neuronal response in nineteen healthy subjects while
they performed an auditory-paced finger tapping task. Subjects performed the
task, after receiving either a nicotine patch or placebo treatment, in a single
blind, crossover design. Compared to placebo, nicotine treatment increased
response in the cerebellar vermis. Increased vermal activity, in the absence of
changes in other task-related regions suggests specificity in nicotine's effects.
PMID- 24358368
TI - Discovering implicit entity relation with the gene-citation-gene network.
AB - In this paper, we apply the entitymetrics model to our constructed Gene-Citation
Gene (GCG) network. Based on the premise there is a hidden, but plausible,
relationship between an entity in one article and an entity in its citing
article, we constructed a GCG network of gene pairs implicitly connected through
citation. We compare the performance of this GCG network to a gene-gene (GG)
network constructed over the same corpus but which uses gene pairs explicitly
connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts
collected from 18,323 seed articles and their references, we identify 25 gene
pairs. A comparison of these pairs with interactions found in BioGRID reveal that
96% of the gene pairs in the GCG network have known interactions. We measure
network performance using degree, weighted degree, closeness, betweenness
centrality and PageRank. Combining all measures, we find the GCG network has more
gene pairs, but a lower matching rate than the GG network. However, combining top
ranked genes in both networks produces a matching rate of 35.53%. By visualizing
both the GG and GCG networks, we find that cancer is the most dominant disease
associated with the genes in both networks. Overall, the study indicates that the
GCG network can be useful for detecting gene interaction in an implicit manner.
PMID- 24358369
TI - Tolerance for nutrient imbalance in an intermittently feeding herbivorous
cricket, the Wellington tree weta.
AB - Organisms that regulate nutrient intake have an advantage over those that do not,
given that the nutrient composition of any one resource rarely matches optimal
nutrient requirements. We used nutritional geometry to model protein and
carbohydrate intake and identify an intake target for a sexually dimorphic
species, the Wellington tree weta (Hemideina crassidens). Despite pronounced
sexual dimorphism in this large generalist herbivorous insect, intake targets did
not differ by sex. In a series of laboratory experiments, we then investigated
whether tree weta demonstrate compensatory responses for enforced periods of
imbalanced nutrient intake. Weta pre-fed high or low carbohydrate: protein diets
showed large variation in compensatory nutrient intake over short (<48 h) time
periods when provided with a choice. Individuals did not strongly defend nutrient
targets, although there was some evidence for weak regulation. Many weta tended
to select high and low protein foods in a ratio similar to their previously
identified nutrient optimum. These results suggest that weta have a wide
tolerance to nutritional imbalance, and that the time scale of weta nutrient
balancing could lie outside of the short time span tested here. A wide tolerance
to imbalance is consistent with the intermittent feeding displayed in the wild by
weta and may be important in understanding weta foraging patterns in New Zealand
forests.
PMID- 24358371
TI - Endocrine correlates of musth in free-ranging Asian elephants (Elephas maximus)
determined by non-invasive faecal steroid hormone metabolite measurements.
AB - The occurrence of musth, a period of elevated levels of androgens and heightened
sexual activity, has been well documented for the male Asian elephant (Elephas
maximus). However, the relationship between androgen-dependent musth and
adrenocortical function in this species is unclear. The current study is the
first assessment of testicular and adrenocortical function in free-ranging male
Asian elephants by measuring levels of testosterone (androgen) and cortisol
(glucocorticoid--a physiological indicator of stress) metabolites in faeces.
During musth, males expectedly showed significant elevation in faecal
testosterone metabolite levels. Interestingly, glucocorticoid metabolite
concentrations remained unchanged between musth and non-musth periods. This
observation is contrary to that observed with wild and captive African elephant
bulls and captive Asian bull elephants. Our results show that musth may not
necessarily represent a stressful condition in free-ranging male Asian elephants.
PMID- 24358370
TI - Rho associated coiled-coil kinase-1 regulates collagen-induced phosphatidylserine
exposure in platelets.
AB - BACKGROUND: The transbilayer movement of phosphatidylserine mediates the platelet
procoagulant activity during collagen stimulation. The Rho-associated coiled-coil
kinase (ROCK) inhibitor Y-27632 inhibits senescence induced but not activation
induced phosphatidylserine exposure. To investigate further the specific
mechanisms, we now utilized mice with genetic deletion of the ROCK1 isoform.
METHODS AND RESULTS: ROCK1-deficient mouse platelets expose significantly more
phosphatidylserine and generate more thrombin upon activation with collagen
compared to wild-type platelets. There were no significant defects in platelet
shape change, aggregation, or calcium response compared to wild-type platelets.
Collagen-stimulated ROCK1-deficient platelets also displayed decreased
phosphorylation levels of Lim Kinase-1 and cofilin-1. However, there was no
reduction in phosphorylation levels of myosin phosphatase subunit-1 (MYPT1) or
myosin light chain (MLC). In an in vivo light/dye-induced endothelial
injury/thrombosis model, ROCK1-deficient mice presented a shorter occlusion time
in cremasteric venules when compared to wild-type littermates (3.16 +/- 1.33 min
versus 6.6 +/- 2.6 min; p = 0.01). CONCLUSIONS: These studies define ROCK1 as a
new regulator for collagen-induced phosphatidylserine exposure in platelets with
functional consequences on thrombosis. This effect was downstream of calcium
signaling and was mediated by Lim Kinase-1 / cofilin-1-induced cytoskeletal
changes.
PMID- 24358372
TI - Infection, disease, and biosocial processes at the end of the Indus Civilization.
AB - In the third millennium B.C., the Indus Civilization flourished in northwest
India and Pakistan. The late mature phase (2200-1900 B.C.) was characterized by
long-distance exchange networks, planned urban settlements, sanitation
facilities, standardized weights and measures, and a sphere of influence over
1,000,000 square kilometers of territory. Recent paleoclimate reconstructions
from the Beas River Valley demonstrate hydro-climatic stress due to a weakened
monsoon system may have impacted urban centers like Harappa by the end of the
third millennium B.C. the impact of environmental change was compounded by
concurrent disruptions to the regional interaction sphere. Climate, economic, and
social changes contributed to the disintegration of this civilization after 1900
B.C. We assess evidence for paleopathology to infer the biological consequences
of climate change and socio-economic disruption in the post-urban period at
Harappa, one of the largest urban centers in the Indus Civilization.
Bioarchaeological evidence demonstrates the prevalence of infection and
infectious disease increased through time. Furthermore, the risk for infection
and disease was uneven among burial communities. Corresponding mortuary
differences suggest that socially and economically marginalized communities were
most vulnerable in the context of climate uncertainty at Harappa. Combined with
prior evidence for increasing levels of interpersonal violence, our data support
a growing pathology of power at Harappa after 2000 B.C. Observations of the
intersection between climate change and social processes in proto-historic cities
offer valuable lessons about vulnerability, insecurity, and the long-term
consequences of short-term strategies for coping with climate change.
PMID- 24358373
TI - Up in the tree--the overlooked richness of bryophytes and lichens in tree crowns.
AB - Assessing diversity is among the major tasks in ecology and conservation science.
In ecological and conservation studies, epiphytic cryptogams are usually sampled
up to accessible heights in forests. Thus, their diversity, especially of canopy
specialists, likely is underestimated. If the proportion of those species differs
among forest types, plot-based diversity assessments are biased and may result in
misleading conservation recommendations. We sampled bryophytes and lichens in 30
forest plots of 20 m * 20 m in three German regions, considering all substrates,
and including epiphytic litter fall. First, the sampling of epiphytic species was
restricted to the lower 2 m of trees and shrubs. Then, on one representative tree
per plot, we additionally recorded epiphytic species in the crown, using tree
climbing techniques. Per tree, on average 54% of lichen and 20% of bryophyte
species were overlooked if the crown was not been included. After sampling all
substrates per plot, including the bark of all shrubs and trees, still 38% of the
lichen and 4% of the bryophyte species were overlooked if the tree crown of the
sampled tree was not included. The number of overlooked lichen species varied
strongly among regions. Furthermore, the number of overlooked bryophyte and
lichen species per plot was higher in European beech than in coniferous stands
and increased with increasing diameter at breast height of the sampled tree.
Thus, our results indicate a bias of comparative studies which might have led to
misleading conservation recommendations of plot-based diversity assessments.
PMID- 24358374
TI - Fetal nicotine exposure increases preference for nicotine odor in early postnatal
and adolescent, but not adult, rats.
AB - Human studies demonstrate a four-fold increased possibility of smoking in the
children of mothers who smoked during pregnancy. Nicotine is the active addictive
component in tobacco-related products, crossing the placenta and contaminating
the amniotic fluid. It is known that chemosensory experience in the womb can
influence postnatal odor-guided preference behaviors for an exposure stimulus. By
means of behavioral and neurophysiologic approaches, we examined whether fetal
nicotine exposure, using mini-osmotic pumps, altered the response to nicotine
odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared
with controls, fetal exposed rats displayed an altered innate response to
nicotine odor that was evident at P17, declined in magnitude by P35 and was
absent at P90--these effects were specific to nicotine odor. The behavioral
effect in P17 rats occurred in conjunction with a tuned olfactory mucosal
response to nicotine odor along with an untoward consequence on the epithelial
response to other stimuli--these P17 neural effects were absent in P35 and P90
animals. The absence of an altered neural effect at P35 suggests that central
mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring
about the altered behavioral response to nicotine odor. Together, these findings
provide insights into how fetal nicotine exposure influences the behavioral
preference and responsiveness to the drug later in life. Moreover, they add to a
growing literature demonstrating chemosensory mechanisms by which patterns of
maternal drug use can be conveyed to offspring, thereby enhancing postnatal
vulnerability for subsequent use and abuse.
PMID- 24358375
TI - Fgf3 and Fgf10a work in concert to promote maturation of the epibranchial
placodes in zebrafish.
AB - Essential cellular components of the paired sensory organs of the vertebrate head
are derived from transient thickenings of embryonic ectoderm known as cranial
placodes. The epibranchial (EB) placodes give rise to sensory neurons of the EB
ganglia that are responsible for relaying visceral sensations form the periphery
to the central nervous system. Development of EB placodes and subsequent
formation of EB ganglia is a multistep process regulated by various extrinsic
factors, including fibroblast growth factors (Fgfs). We discovered that two Fgf
ligands, Fgf3 and Fgf10a, cooperate to promote EB placode development. Whereas EB
placodes are induced in the absence of Fgf3 and Fgf10a, they fail to express
placode specific markers Pax2a and Sox3. Expression analysis and mosaic rescue
experiments demonstrate that Fgf3 signal is derived from the endoderm, whereas
Fgf10a is emitted from the lateral line system and the otic placode. Further
analyses revealed that Fgf3 and Fgf10a activities are not required for cell
proliferation or survival, but are required for placodal cells to undergo
neurogenesis. Based on these data, we conclude that a combined loss of these Fgf
factors results in a failure of the EB placode precursors to initiate a
transcriptional program needed for maturation and subsequent neurogenesis. These
findings highlight the importance and complexity of reiterated Fgf signaling
during cranial placode formation and subsequent sensory organ development.
PMID- 24358377
TI - Dramatic variability of the carbonate system at a temperate coastal ocean site
(Beaufort, North Carolina, USA) is regulated by physical and biogeochemical
processes on multiple timescales.
AB - Increasing atmospheric carbon dioxide (CO2) from anthropogenic sources is
acidifying marine environments resulting in potentially dramatic consequences for
the physical, chemical and biological functioning of these ecosystems. If current
trends continue, mean ocean pH is expected to decrease by ~0.2 units over the
next ~50 years. Yet, there is also substantial temporal variability in pH and
other carbon system parameters in the ocean resulting in regions that already
experience change that exceeds long-term projected trends in pH. This points to
short-term dynamics as an important layer of complexity on top of long-term
trends. Thus, in order to predict future climate change impacts, there is a
critical need to characterize the natural range and dynamics of the marine
carbonate system and the mechanisms responsible for observed variability. Here,
we present pH and dissolved inorganic carbon (DIC) at time intervals spanning 1
hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet,
Beaufort NC USA) to characterize the carbonate system at multiple time scales.
Daily and seasonal variation of the carbonate system is largely driven by
temperature, alkalinity and the balance between primary production and
respiration, but high frequency change (hours to days) is further influenced by
water mass movement (e.g. tides) and stochastic events (e.g. storms). Both annual
(~0.3 units) and diurnal (~0.1 units) variability in coastal ocean acidity are
similar in magnitude to 50 year projections of ocean acidity associated with
increasing atmospheric CO2. The environmental variables driving these changes
highlight the importance of characterizing the complete carbonate system rather
than just pH. Short-term dynamics of ocean carbon parameters may already exert
significant pressure on some coastal marine ecosystems with implications for
ecology, biogeochemistry and evolution and this shorter term variability layers
additive effects and complexity, including extreme values, on top of long-term
trends in ocean acidification.
PMID- 24358376
TI - The roles of the catalytic and noncatalytic activities of Rpd3L and Rpd3S in the
regulation of gene transcription in yeast.
AB - In budding yeasts, the histone deacetylase Rpd3 resides in two different
complexes called Rpd3L (large) and Rpd3S (small) that exert opposing effects on
the transcription of meiosis-specific genes. By introducing mutations that
disrupt the integrity and function of either Rpd3L or Rpd3S, we show here that
Rpd3 function is determined by its association with either of these complexes.
Specifically, the catalytic activity of Rpd3S activates the transcription of the
two major positive regulators of meiosis, IME1 and IME2, under all growth
conditions and activates the transcription of NDT80 only during vegetative
growth. In contrast, the effects of Rpd3L depends on nutrients; it represses or
activates transcription in the presence or absence of a nitrogen source,
respectively. Further, we show that transcriptional activation does not correlate
with histone H4 deacetylation, suggesting an effect on a nonhistone protein.
Comparison of rpd3-null and catalytic-site point mutants revealed an inhibitory
activity that is independent of either the catalytic activity of Rpd3 or the
integrity of Rpd3L and Rpd3S.
PMID- 24358378
TI - From the Editor-in-Chief: Scope Expansion and New Editor-in-Chief for 2014.
PMID- 24358379
TI - The CREATE Method Does Not Result in Greater Gains in Critical Thinking than a
More Traditional Method of Analyzing the Primary Literature.
AB - Analysis of the primary literature in the undergraduate curriculum is associated
with gains in student learning. In particular, the CREATE (Consider, Read,
Elucidate hypotheses, Analyze and interpret the data, and Think of the next
Experiment) method is associated with an increase in student critical thinking
skills. We adapted the CREATE method within a required cell biology class and
compared the learning gains of students using CREATE to those of students
involved in less structured literature discussions. We found that while both sets
of students had gains in critical thinking, students who used the CREATE method
did not show significant improvement over students engaged in a more traditional
method for dissecting the literature. Students also reported similar learning
gains for both literature discussion methods. Our study suggests that, at least
in our educational context, the CREATE method does not lead to higher learning
gains than a less structured way of reading primary literature.
PMID- 24358380
TI - Context matters: volunteer bias, small sample size, and the value of comparison
groups in the assessment of research-based undergraduate introductory biology lab
courses.
AB - The shift from cookbook to authentic research-based lab courses in undergraduate
biology necessitates the need for evaluation and assessment of these novel
courses. Although the biology education community has made progress in this area,
it is important that we interpret the effectiveness of these courses with caution
and remain mindful of inherent limitations to our study designs that may impact
internal and external validity. The specific context of a research study can have
a dramatic impact on the conclusions. We present a case study of our own three
year investigation of the impact of a research-based introductory lab course,
highlighting how volunteer students, a lack of a comparison group, and small
sample sizes can be limitations of a study design that can affect the
interpretation of the effectiveness of a course.
PMID- 24358381
TI - An argument and plan for promoting the teaching and learning of neglected
tropical diseases.
AB - Neglected tropical diseases constitute a significant public health burden,
affecting over one billion people globally, yet this group of diseases is
underrepresented in the appropriation of both monetary and intellectual capital
for developing improved therapies and public health campaigns. The topic of
neglected tropical diseases has been similarly marginalized in the biology
classrooms of our nation's high schools and colleges, despite offering an
opportunity to teach and learn about a diverse area of microbiology with far
reaching public health, social, and economic implications. Discussed herein is an
argument for increasing the representation of neglected tropical diseases in
microbiology education as a means to generate increased interest in these
diseases among the generation of future researchers and policy-makers, and to
promote interdisciplinary learning, civic engagement, and critical thinking.
PMID- 24358382
TI - Inquiry-based learning: inflammation as a model to teach molecular techniques for
assessing gene expression.
AB - This laboratory module simulates the process used by working scientists to ask
and answer a question of biological interest. Instructors facilitate acquisition
of knowledge using a comprehensive, inquiry-based approach in which students
learn theory, hypothesis development, experimental design, and data
interpretation and presentation. Using inflammation in macrophages as a model
system, students perform a series of molecular biology techniques to address the
biological question: "Does stimulus 'X' induce inflammation?" To ask this
question, macrophage cells are treated with putative inflammatory mediators and
then assayed for evidence of inflammatory response. Students become familiar with
their assigned mediator and the relationship between their mediator and
inflammation by conducting literature searches, then using this information to
generate hypotheses which address the effect of their mediator on induction of
inflammation. The cellular and molecular approaches used to test their hypotheses
include transfection and luciferase reporter assay, immunoblot, fluorescence
microscopy, enzyme-linked immunosorbent assay, and quantitative PCR. Quantitative
and qualitative reasoning skills are developed through data analysis and
demonstrated by successful completion of post-lab worksheets and the generation
and oral presentation of a scientific poster. Learning objective assessment
relies on four instruments: pre-lab quizzes, post-lab worksheets, poster
presentation, and posttest. Within three cohorts (n = 85) more than 95% of our
students successfully achieved the learning objectives.
PMID- 24358383
TI - What's Downstream? A Set of Classroom Exercises to Help Students Understand
Recessive Epistasis.
AB - Undergraduate students in genetics and developmental biology courses often
struggle with the concept of epistasis because they are unaware that the logic of
gene interactions differs between enzymatic pathways and signaling pathways. If
students try to develop and memorize a single simple rule for predicting
epistatic relationships without taking into account the nature of the pathway
under consideration, they can become confused by cases where the rule does not
apply. To remedy this problem, we developed a short pre-/post-test, an in-class
activity for small groups, and a series of clicker questions about recessive
epistasis in the context of a signaling pathway that intersects with an enzymatic
pathway. We also developed a series of homework problems that provide deliberate
practice in applying concepts in epistasis to different pathways and experimental
situations. Students show significant improvement from pretest to posttest, and
perform well on homework and exam questions following this activity. Here we
describe these materials, as well as the formative and summative assessment
results from one group of students to show how the activities impact student
learning.
PMID- 24358384
TI - Laboratory activity to effectively teach introductory geomicrobiology concepts to
non-geology majors.
AB - We have designed a three-week experiment that can complement any microbiology
course, to teach main geomicrobiology concepts for non-geology majors. One of the
most difficult concepts for non-geology majors to comprehend is how bacteria
serve as a platform for different mineralization reactions. In our three-week
laboratory practice, students learn the main principles and conditions required
for an induced bacterial mineralization. Upon completion of the laboratory
experience, students will: 1) learn how microbial-induced mineralization (such as
calcium carbonate formation) is affected by differential media and growth
conditions; 2) understand how bacterial physiology affects any induced in situ or
in vitro mineralization; 3) comprehend how growing conditions and bacterial
physiologies interrelate, resulting in differential crystal formation. The
teaching-learning process was assessed using a pre-/posttest with an increase
from 26% to 76% in the number of positive answers from the students. We also
measured the students' proficiency while conducting specific technical tasks,
revealing no major difficulties while conducting the experiments. A final
questionnaire was provided with satisfactory evaluations from the students
regarding the organization and content of the practices. 84-86% of the students
agreed that the exercises improved their knowledge in geomicrobiology and would
like to attend similar laboratories in the future. Such response is the best
indicator that the laboratory practice can be implemented in any
undergraduate/graduate microbiology course to effectively teach basic
geomicrobiology concepts to non-geology majors.
PMID- 24358385
TI - Making connections: service-learning in introductory cell and molecular biology.
AB - This report describes service-learning in a first-year majors biology course in
which students serve throughout the semester with community partners for an
average of 25 hours/student. All of the partnerships are based on providing
engaging hands-on biology activities for youth in underserved urban areas
surrounding the campus. Students in the course have designed new lessons and
activities, supported biology labs, mentored younger students, and facilitated
afterschool science clubs. Throughout the course, integration between the
students' service experience in the community and their learning in the course is
emphasized. This is accomplished in multiple ways including class discussion,
group activities, feedback from the instructor and teaching assistant, and weekly
blogs. A three-year average of anonymous university-wide course evaluations
suggested that students in this service-learning course considered their biology
course to be highly rigorous. In both blogs and anonymous surveys students
reported that their service and its integration with the course not only advanced
their professional skills and sense of community engagement, but also enhanced
their learning in biology.
PMID- 24358387
TI - Attack of the killer fungus: a hypothesis-driven lab module.
AB - Discovery-driven experiments in undergraduate laboratory courses have been shown
to increase student learning and critical thinking abilities. To this end, a lab
module involving worm capture by a nematophagous fungus was developed. The goals
of this module are to enhance scientific understanding of the regulation of worm
capture by soil-dwelling fungi and for students to attain a set of established
learning goals, including the ability to develop a testable hypothesis and search
for primary literature for data analysis, among others. Students in a ten-week
majors lab course completed the lab module and generated novel data as well as
data that agrees with the published literature. In addition, learning gains were
achieved as seen through a pre-module and post-module test, student self
assessment, class exam, and lab report. Overall, this lab module enables students
to become active participants in the scientific method while contributing to the
understanding of an ecologically relevant model organism.
PMID- 24358386
TI - Cooperative Learning through Team-Based Projects in the Biotechnology Industry.
AB - We have developed a cooperative-learning, case studies project model that has
teams of students working with biotechnology professionals on company-specific
problems. These semester-long, team-based projects can be used effectively to
provide students with valuable skills in an industry environment and experience
addressing real issues faced by biotechnology companies. Using peer-evaluations,
we have seen improvement in students' professional skills such as time
management, quality of work, and level of contribution over multiple semesters.
This model of team-based, industry-sponsored projects could be implemented in
other college and university courses/programs to promote professional skills and
expose students to an industry setting.
PMID- 24358388
TI - A Small-Group Activity Introducing the Use and Interpretation of BLAST.
AB - As biological sequence data are generated at an ever increasing rate, the role of
bioinformatics in biological research also grows. Students must be trained to
complete and interpret bioinformatic searches to enable them to effectively
utilize the trove of sequence data available. A key bioinformatic tool for
sequence comparison and genome database searching is BLAST (Basic Local Alignment
Search Tool). BLAST identifies sequences in a database that are similar to the
entered query sequence, and ranks them based on the length and quality of the
alignment. Our goal was to introduce sophomore and junior level undergraduate
students to the basic functions and uses of BLAST with a small group activity
lasting a single class period. The activity provides students an opportunity to
perform a BLAST search, interpret the data output, and use the data to make
inferences about bacterial cell envelope structure. The activity consists of two
parts. Part 1 is a handout to be completed prior to class, complete with video
tutorial, that reviews cell envelope structure, introduces key terms, and allows
students to familiarize themselves with the mechanics of a BLAST search. Part 2
consists of a hands-on, web-based small group activity to be completed during the
class period. Evaluation of the activity through student performance assessments
suggests that students who complete the activity can better interpret the BLAST
output parameters % query coverage and % max identity. While the topic of the
activity is bacterial cell wall structure, it could be adapted to address other
biological concepts.
PMID- 24358389
TI - Color-removal by microorganisms isolated from human hands.
PMID- 24358390
TI - Semester-long assessment of aseptic technique in microbiology labs.
PMID- 24358391
TI - Development of a bi-disciplinary course in forensic science.
PMID- 24358392
TI - Blast a biofilm: a hands-on activity for school children and members of the
public.
PMID- 24358393
TI - A survey tool for assessing student expectations early in a semester.
PMID- 24358394
TI - Confluence: a seminar series as a teaching tool.
PMID- 24358395
TI - Presenting fake figures: a tool to teach effective scientific figure design.
PMID- 24358396
TI - Cover your cough! A short and simple activity to demonstrate the antimicrobial
effect of desiccation.
PMID- 24358397
TI - Engineering your own superbug: a useful assignment to evaluate real learning
comprehension in microbiology classes.
PMID- 24358398
TI - Connecting music, art, and science for increased creativity and topic engagement.
PMID- 24358399
TI - A New Twist to the Kirby-Bauer Antibiotic Susceptibility Test Activity-Increasing
Antibiotic Sensitivity of Pseudomonas fluorescens through Thermal Stress.
PMID- 24358400
TI - Observing Chemotaxis in Vibrio fischeri Using Soft Agar Assays in an
Undergraduate Microbiology Laboratory.
PMID- 24358401
TI - Gamification of the laboratory experience to encourage student engagement.
PMID- 24358403
TI - Using a "microbe minute" to improve class attendance and increase course
interest.
PMID- 24358402
TI - Using scientific abstracts to measure learning outcomes in the biological
sciences.
PMID- 24358405
TI - The Impact of the Unified Protocol for Emotional Disorders on Quality of Life.
AB - It has become increasingly clear that mental health is more than just the absence
of psychopathology and that there is clinical utility in examining positive
aspects of mental health. The present study examined the effects of the Unified
Protocol for Transdiagnostic Treatment of Emotional Disorders on quality of life
in a randomized controlled trial that included individuals with a diverse range
of emotional disorders. Results indicated that the Unified Protocol produced
significant increases in quality of life when examining both within-individual
effect sizes and between-conditions effect sizes compared to a waitlist
condition. Furthermore, results indicated that post-treatment levels of quality
of life predicted levels of functional impairment independently of diagnostic
severity. These results provide further evidence of the importance of examining
indicators of mental health in conjunction with markers of psychopathology and
provide promising evidence that the Unified Protocol may promote improved mental
health in addition to treating psychopathology.
PMID- 24358406
TI - Prevention of Early-onset Neonatal Group B Streptococcal Disease.
AB - Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is an
opportunistic pathogen that colonizes the gastrointestinal and genitourinary
tracts of up to 50% of healthy adults and newborns; it is responsible for
significant morbidity and mortality. Early detection can be used to establish the
use of antibiotic prophylaxis to significantly reduce neonatal sepsis. This
article reviews methods of detection and prevention of GBS infection in the
neonate.
PMID- 24358407
TI - Global endometrial ablation in the presence of essure(r) microinserts.
AB - Abnormal uterine bleeding (AUB) affects 30% of women at some time during their
reproductive years and is one of the most common reasons a woman sees a
gynecologist. Many women are turning to endometrial ablation to manage their AUB.
This article reviews the data relating to the available endometrial ablation
techniques performed with hysteroscopic sterilization, and focuses on data from
patients who had Essure(r) (Conceptus, San Carlos, CA) coils placed prior to
performance of endometrial ablation. Reviewed specifically are data regarding
safety and efficacy of these two procedures when combined. Data submitted to the
US Food and Drug Administration for the three devices currently approved are
reviewed, as well as all published case series. Articles included were selected
based on a PubMed search for endometrial ablation (also using the brand names of
the different techniques currently available), hysteroscopic sterilization, and
Essure.
PMID- 24358408
TI - Preparing for Global Women's Health Work.
AB - Interest in global maternal health has steadily increased over the past decade.
Medical schools are offering courses on this subject, residencies are
incorporating international elective rotations into their practices, and retiring
practitioners are opting to spend a year or two in low-resource settings.
Although interest is growing, sometimes wellmeaning health practitioners are not
entirely prepared for their new experience. Prior to departure, a multistep
process is necessary to prepare physicians for living and practicing overseas.
PMID- 24358409
TI - Use of intravenous recombinant tissue plasminogen activator in patients with
borderline elevation of international normalized ratio.
AB - OBJECTIVE: To determine the rates of symptomatic intracerebral hemorrhages
(sICH), parenchymal hematoma type 2 (PH2), and favorable outcomes in patients
with borderline elevation of international normalized ratio (INR) or recent
anticoagulation use prior to treatment with intravenous recombinant tissue
plasminogen activator (IV rt-PA) for acute ischemic stroke. METHODS: Consecutive
patients with acute ischemic stroke that received IV rt-PA were identified.
History of recent use of anticoagulation and the INR at presentation and after
use of thrombolytics, up to 72 h was recorded. Neuroimaging and clinical charts
were reviewed for evidence of sICH. Outcomes were recorded at the time of
discharge and on follow-up up to 6 months using the modified Rankin scale (mRS).
RESULTS: A total of 106 patients (mean age was 65.95 +/- 15.29 years and 55.67%
were men) were identified. Of these, 12 (11.3%) patients had initial INR
elevation (1.2-1.7) and 12 (11.3%) patients that had recently received oral
anticoagulation. The rate of PH2 was higher in patients on anticoagulation or
with elevated initial INR compared to patients with normal INR and no history of
anticoagulation (15.79% versus 2.30%, P = 0.023). In subgroup analyses, elevation
of INR during the first 24 h and history of recent use of anticoagulation in a
different analysis inversely correlated with favorable outcomes at discharge and
at follow-up. CONCLUSION: Borderline elevation in INR or recent use of
anticoagulation before thrombolytic use can increase the rate of ICH in patients
treated with IV rt-PA for acute ischemic stroke. These patients should cautiously
receive thrombolytics for acute ischemic stroke as per the AHA/ASA Stroke Council
guidelines.
PMID- 24358411
TI - Case Report: Thrombosis of a ruptured fusiform basilar apex aneurysm after
stenting and selective coiling.
PMID- 24358410
TI - Patterns of collateral formation in basilar artery steno-occlusive diseases.
AB - BACKGROUND: Augmentation of collateral flow is proposed as a method to reduce
ischemic injury in the posterior circulation. However, collateral formation in
basilar artery stenosis (BAS) and basilar artery occlusion (BAO) has not been
studied thoroughly. METHODS: We identified 24 consecutive patients admitted over
a 4-year period with angiographically demonstrated BAS of more than 50% or
occlusion. Angiographic images were reviewed for pattern of collaterals by a
blinded reviewer. A new grading system by Qureshi [1] (Qureshi AI (2012) J
Neuroimaging in press) was utilized for grading. Grades I and II had retrograde
filling of the basilar artery through PCA with or without filling of the superior
cerebellar artery, respectively. Grades III and IV were bilateral or unilateral
anastomoses of cerebellar arteries or PCAs, respectively. Risk factors such as
age, gender, race/ethnicities, co-morbidities, NIHSS sore on admission and
discharge, tPA administration, in-hospital complications, and discharge status
measured by the modified Rankin score were ascertained. RESULTS: THE COLLATERALS
WERE CATEGORIZED AS: Grade I A (n = 8), Grade IIIA (n = 5), and none (n = 11). No
patient had Grade II collaterals. Grade IA collaterals were more frequent in
patients with BAO than those with BAS. The rate of good outcomes (mRS 0-2) at
discharge was significantly higher among patients with IA collaterals compared
with patients with grade IIIA collaterals (62% vs. 20%). The rate of good
outcomes was 54% of patients without collaterals. CONCLUSIONS: The pattern of
collateral formation in BAS and BAO varies and is associated with patient
outcomes.
PMID- 24358412
TI - Thrombectomy for delayed basilar stent occlusion with good outcome.
AB - ABSTRACT: Neurovascular stents have revolutionized the endovascular treatment of
wide-necked and fusiform aneurysms; however, potential in-stent thrombosis
resulting in devastating strokes-complicates their use. Interventionalists using
these devices must be aware of treatment options for such events. We present the
case of a 46-year-old man who underwent stent-supported embolization of an
incidental basilar aneurysm followed by in-stent thrombosis 6 weeks later. Though
he presented at that time after 24 h of symptom onset with complete occlusion of
the basilar artery, delayed thrombectomy and thrombolysis resulted in a good
clinical outcome. LIST OF ABBREVIATIONS: IVintravenousACTactivated coagulation
timeDWI MRIdiffusion weighted magnetic resonance imagingIAintra-arterialtPAtissue
plasminogen activatorICHintracranial hemorrhage. LIST OF PROPRIETARY DEVICES
CITED IN TEXT: Enterprise Vascular Reconstructive Device (r), Codman
Neurovascular, Raynham, MA Excelsior SL 10 microcatheter, Target
Therapeutics/Stryker, Fremont, CA Prowler Plus Select microcatheter, Codman
Neurovascular MPD Envoy catheter, Codman Neurovascular Penumbra .032" Reperfusion
catheter, Penumbra Inc., San Leandro, CA Transend .014" microwire, Target/Stryker
Merci Concentric Retriever (r), Concentric Medical/Stryker, Mountainview, CA.
PMID- 24358414
TI - Marginal sinus fistula supplied exclusively by vertebral artery feeders.
AB - A 54-year-old woman is reported with severe pulsatile tinnitus. Digital
subtraction angiography demonstrated dural arteriovenous fistula of the marginal
sinus with feeders arising exclusively from bilateral vertebral arteries. Patient
underwent successful transarterial Onyx embolization with complete angiographic
and clinical cure.
PMID- 24358413
TI - Cost-effectiveness analysis of intracranial stent placement versus contemporary
medical management in patients with symptomatic intracranial artery stenosis.
AB - BACKGROUND: Intracranial angioplasty and stent placement has been increasingly
evaluated as a new method for treatment of symptomatic intracranial stenosis in
select patients. The Food and Drug Administration (FDA) has approved intracranial
stent treatment of symptomatic atherosclerotic intracranial lesions. PURPOSE: To
determine the cost-effectiveness of intracranial artery stent placement compared
with contemporary medical management for secondary stroke prevention among
patients with symptomatic intracranial stenosis. METHODS: Clinical outcome data
were obtained from the aspirin treatment arm of the Comparison of Warfarin and
Aspirin for Symptomatic Intracranial Disease (WASID) trial (n = 280) and 12 case
series (n = 216) of patients who underwent stent placement of symptomatic
intracranial stenosis with comparable characteristics. Total cost of procedure
and medical management-only was calculated using the rates of major stroke, minor
stroke, or death in each group. All costs are expressed in 2010 US$. The quality
adjusted life-year (QALY) of each intervention strategy was estimated using the
frequency of the outcomes of major and minor stroke, death, and baseline health.
An incremental cost-effectiveness ratio (ICER) was formulated for a 1-year
period. RESULTS: The total rate of stroke at one year was 10.2% (6.1-14.2%) and
the rate of all-cause mortality was 3.7% (1.2-6.2%) in the stent group. The
corresponding annualized rates of stroke and all-cause mortality in the medical
management-only group were 15% (10.8-19.2%) and 2.4% (0.6-4.2%), respectively.
The calculated net costs at one year for intracranial stent placement and
contemporary medical management were US$16,898 and US$3,468, respectively.
Overall, QALYs for the two groups were 0.82 and 0.81 (in a range of 0 to 0.89
corresponding to death and baseline health), respectively. The cost per QALY
gained after intracranial stent placement and contemporary medical therapy was
US$20,542 and US$4,265, respectively. The corresponding ICER for stent versus
medical treatment alone was US$1,416,268. CONCLUSION: The reduced risk of stroke
following intracranial stent placement is offset by significantly higher
procedure-associated net costs. Select procedures in patients with symptomatic
stenosis of 70% or greater are more likely to be cost-effective.
PMID- 24358415
TI - A randomized trial comparing primary angioplasty versus stent placement for
symptomatic intracranial stenosis.
AB - BACKGROUND: Both primary angioplasty alone and angioplasty with a self-expanding
stent have been compared in non-randomized concurrent clinical studies that
suggest equivalent results. However, there is no randomized trial that has
compared the two procedures in patients with symptomatic high grade intracranial
stenosis. OBJECTIVE: The primary aim of the randomized trial was to compare the
clinical and angiographic efficacy of primary angioplasty and angioplasty
followed by stent placement in preventing restenosis, stroke, requirement for
second treatment, and death in patients with symptomatic intracranial stenosis.
METHODS: The study prospectively evaluated efficacy and safety of the two
existing neurointerventional techniques for treatment of moderate intracranial
stenosis (stenosis >= 50%) with documented failure of medical treatment or severe
stenosis (>=70%) with or without failure of medical treatment. RESULTS: A total
of 18 patients were recruited in the study (mean age [+/-SD] was 64.7 +/- 15.1
years); out of these, 12 were men. Of these 18, 10 were treated with primary
angioplasty and 8 were treated with angioplasty followed by self-expanding stent.
The technical success rates of intracranial angioplasty and stent placements
defined as ability to achieve <30% residual stenosis when assessed by immediate
post-procedure angiography was 5 of 10 and 5 of 8 patients, respectively. The
total fluoroscopic time (mean [+/-SD]) was lower in patients undergoing primary
angioplasty 37 [+/-11] min versus those undergoing angioplasty followed by self
expanding stent 42 [+/-15] min, P = 0.4321. The stroke and death rate within 1
month was very low in both patient groups (1 of 10 versus 0 of 8 patients). One
patient randomized to stent placement continued to have recurrent ischemic
symptoms requiring another angioplasty in the vertebral artery on post-procedure
Day 2. CONCLUSIONS: The trial suggests that a randomized trial comparing primary
angioplasty to angioplasty followed by stent placement is feasible. The immediate
procedural outcomes with primary angioplasty are comparable to stent placement
and warrant further studies.
PMID- 24358416
TI - Duplex ultrasound assisted endovascular revascularization of chronic internal
carotid artery occlusion: technical note.
AB - Carotid artery occlusion is a major risk factor for ischemic stroke. Endovascular
treatment of carotid artery occlusion in high-risk patients offers a therapeutic
option to reduce subsequent ischemic events. The technical success and avoidance
of complications of the endovascular recanalization of occluded carotid artery is
contingent on proper visualization of the vessel wall. To highlight the value of
duplex ultrasound guidance, we herein described the procedural details of the use
of ultrasound guidance for characterization and visualization of the endovascular
devices as well as the vessel wall during endovascular revascularization. Patient
was a 54-year-old woman, diagnosed with carotid occlusion with recurrent
symptomatic episodes. Endovascular revascularization was successfully performed
by ultrasound assistance upon traversing the occluded segment and accurate
deployment of stent. The patient was followed for 3 months and has not
experienced any ischemic symptoms. Duplex ultrasound guidance helps preventing
the vessel wall injury and dissection during revascularization of chronically
occluded carotid artery. Ultrasound guidance may improve the outcomes of the
endovascular procedures in high-risk patients with carotid occlusion.
PMID- 24358417
TI - Readmission within 1 month of discharge among patients with acute ischemic
stroke: results of the University HealthSystem Consortium Stroke Benchmarking
study.
AB - BACKGROUND: The University HealthSystem Consortium (UHC) recently conducted a
benchmarking project to identify variations in processes of care and clinical
resource management, identify new patterns in practice, and distinguish
opportunities for improvement among UHC hospitals. METHODS: We performed this
analysis to determine the rate of and factors associated with readmission within
1 month of discharge among patients with acute ischemic stroke. A retrospective
review of 40 consecutive ischemic stroke cases meeting inclusion criteria and
discharge between January 1st and June 30th, 2004 was conducted in 32 hospitals.
We performed a multivariate analysis to identify demographic and clinical factors
associated with readmission among patients with ischemic stroke. RESULTS: A total
of 1018 patients (mean age 66 years, range 18-98 years), who were discharged from
the hospital and had follow-up available, were analyzed. A total of 90 (9%) of
these patients were readmitted within 1 month of discharge. Common reasons for
readmission were recurrent stroke (24%), infection (12%), chest pain or
myocardial infarction (10%), worsening of stroke symptoms (7%), arrhythmias (7%),
and congestive heart failure (3%). In univariate analysis, older patients (P =
0.03) and those discharged home without health care were more likely to be
readmitted (P = 0.04). In the multivariate analysis, age was the only predictor
for readmission. For each decade older age, there was a 19% increase in odds of
readmission. Patient's race/ethnicity, presence of cardiovascular risk factors,
and severity of stroke, insurance status, neurology consultation, discharge
destination were not associated with readmission. CONCLUSIONS: In the present
multicenter study, 9% of the discharged patients with ischemic stroke were
readmitted within a 1 month. Several etiologies for readmission were identified
to assist in implementing quality improvement strategies.
PMID- 24358418
TI - Manual external carotid artery manipulation for failed device advance through the
stent in carotid artery stent placement. A technical note.
AB - We report herein the usefulness of a manual external carotid artery manipulation
for failed advancement of devices through the stent in carotid artery stent (CAS)
placement with open cell type stent and filter type distal protection device. In
all, 22 consecutive patients underwent CAS with filter type protection device
between April 2008 and December 2009 in our institution, and failed advancement
of the devices through the stent occurred in 4 patients (18%). For all the 4
patients, the devices could be navigated normally through the stent under the
manual external carotid artery manipulation. In cases with failed device advance
in CAS, this maneuver would be one of the methods to resolve this.
PMID- 24358419
TI - Sex, Health Behaviors and Social Support: Functional Decline among Older
Diabetics.
AB - PROBLEM STATEMENT: Men and women experience pronounced differences in functional
decline as they age. The mechanisms behind these differences remain unclear,
particularly among chronically ill populations. Drawing on the theory of the
disablement process, this research examines sex differences in functional
decline, focusing on two mechanisms suggested by the literature to partially
mediate these disparities: health behaviors and social support. APPROACH: Data
from diabetics aged 50 and older from the Health and Retirement Study (n = 2,493)
were examined for change in functional status over a 10-year period. Multivariate
longitudinal multi-level models were conducted to analyze (1) health behavior (2)
social support; and (3) a full model with health behavior and social support
together, followed by a separate analysis using sex interaction terms. RESULTS:
Women and men both experienced functional decline over time. In the models that
examined health behaviors and social support separately, women experienced
steeper rates of decline. In the full model (which included health behaviors and
social support together), men experienced a steeper rate of decline relative to
women. The analyses suggest that it is the combination of health and social
characteristics (largely through engagement in socially supportive activities
that promote health) that are protective against functional decline.
CONCLUSION/RECOMMENDATIONS: As diabetic men experienced a steeper rate of
functional decline than diabetic women once health behaviors and social support
were both held constant, future research must examine (a) how these protective
factors operate in tandem to protect against disablement of women with diabetes;
and (b) how clinical and social policy can promote multi-pronged interventions to
improve health behaviors in supportive contexts. Such research will benefit from
multi-disciplinary collaborations.
PMID- 24358420
TI - The effects of acute administration of Chinese aphrodisiacs sold in Blantyre City
on sperm characteristics and fertility profile in guinea pigs.
AB - BACKGROUND: Chinese aphrodisiacs have become popular remedy for sexual
dysfunction and improvement of libido in men in Malawi. However, selling of these
drugs seems not to be well regulated. Probably the aphrodisiacs that are
currently on the market have unknown efficacy, potency and safety profiles. The
aim of this study was to assess the efficacy of imported Chinese aphrodisiacs
using guinea pigs as a model. MATERIALS AND METHODS: Two types of drugs were
purchased from vendors in Blantyre City. Tonic tea, which was purported to
improve erectile function and libido, and sperm multiplier tablets which were
claimed to increase the sperm count. The tonic tea was prepared by soaking one
tea bag in 100ml boiling water. The tea was cooled and administered to eight male
experimental animals in varying doses. Each animal was introduced into a separate
cage with a female guinea pig. Sexual behaviour such as mounting, sniffing behind
the female were observed and recorded. Each sperm multiplier tablet was dissolved
in distilled water and administered to the experimental animals in the morning
and evening for seven days. At the end of the treatment, the experimental and
control animals were sacrificed, their semen collected and analysed sperm
motility, concentration and morphology. RESULTS: For the tonic tea, there were no
statistical differences between the experimental and the control animals in terms
of the number of mountings and sniffing behind the female. The sperm multiplier
drug showed statistically significant differences between the experimental and
the control animals in terms of the sperm motility (78.24 +/- 1.35 vs. 86.54 +/-
1.88, p< 0.05), and concentration (54.28 +/- 1.24 vs. 67.59 +/- 2.12, p<0.05).
CONCLUSION: The tonic tea did not show any efficacy in improving erection and
libido. The sperm multiplier tablets, purported to increase sperm production,
significantly increased the sperm motility, sperm concentration in the treated
animals.
PMID- 24358421
TI - Biopsy case mix and diagnostic yield at a Malawian central hospital.
AB - Cancer is a major disease burden worldwide resulting in high morbidity and
mortality. It is the leading cause of mortality in developed countries and is one
of the three leading causes of death for adults in developing countries.
Pathological examination of tissue biopsies with histological confirmation of a
correct cancer diagnosis is central to cancer care. Without an accurate and
specific pathologic diagnosis, effective treatment cannot be planned or
delivered. In addition, there are marked geographical variations in incidence of
cancer overall, and of the specific cancers seen. Much of the published
literature on cancer incidence in developing countries reflects gross estimates
and may not reflect reality. Performing baseline studies to understand these
distributions lays the groundwork for further research in this area of cancer
epidemiology. Our current study surveys and ranks cancer diagnoses by individual
anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest
teaching and referral hospital in Malawi. A retrospective study was conducted
reviewing available pathology reports over a period of one full year from January
2010 to December 2010 for biopsies from patients suspected clinically of having
cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical
sites. The oesophagus was the most common biopsied site followed by breast,
bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found
in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%;
adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%)
and stomach (37.6%). Our study demonstrates that the yield of biopsy for
clinically suspected malignancy was greater than 50% for the 11 most common sites
and provides a current survey of cancer types by site present in the population
reporting to our hospital.
PMID- 24358422
TI - Reproductive decisions of couples living with HIV in Malawi: what can we learn
for future policy and research studies?
AB - BACKGROUND: The rapid scale-up of free antiretroviral therapy has lead to decline
in adult mortality at the population level and reduction of vertical
transmission. Consequently, some couples living with HIV are maintaining their
reproductive decisions; marrying and having children. This paper analyses
policies and guidelines on HIV, AIDS and sexual and reproductive health in Malawi
for content on marriage and childbearing for couples living with HIV. METHODS: A
qualitative study using interpretive policy analysis approach was conducted from
July to December 2010 in two phases. First, data on access to HIV, AIDS and
sexual and reproductive health services were collected using in-depth interviews
with twenty couples purposively sampled in matrilineal Chiradzulu and patrilineal
Chikhwawa communities. Secondly, data were collected from Malawi policies and
guidelines on HIV, AIDS and sexual and reproductive health. The documents were
reviewed for content on marriage and childbearing for couples living with HIV.
Data were analysed using framework approach for applied policy analysis. RESULTS:
Four categories emerged from each phase. From the study, we extracted health
workers attitudes, weak linkage between HIV, AIDS and sexual and reproductive
health services, contradictory messages between media and the hospitals and lack
of information as factors directly related to guidelines and policies. Analysis
of guidelines and policies showed non-prescriptiveness on issues of HIV, AIDS and
reproduction: they do not reflect the social cultural experiences of couples
living with HIV. In addition, there is; lack of clinical guidelines, external
influence on adoption of the policies and guidelines and weak linkages between
HIV and AIDS and sexual and reproductive health services. CONCLUSION: This
synthesis along with more detailed findings which are reported in other published
articles, provide a strong basis for updating the policies and development of
easy-to-follow guidelines in order to effectively provide services to couples
living with HIV in Malawi.
PMID- 24358424
TI - Exit ventriculoperitoneal shunt; enter endoscopic third ventriculostomy (ETV):
contemporary views on hydrocephalus and their implications on management.
AB - Hydrocephalus has been known to affect humans since the birth of human medicine
as it is described by Hippocrates. The management of this condition is however
still dodged by challenges due to a poor understanding of its pathophysiology.
The ventriculoperitoneal shunt presents considerable problems especially with
respect to infection and shunt malfunction. Low income countries, that currently
face the greater burden of paediatric hydrocephalus. experience an increased
challenge with ventriculoperitoneal shunts due to a shortage of qualified
personnel to handle shunt complications. Recent advances in neuro-endoscopic
surgery have presented opportunities for alternative treatment options for
hydrocephalus such as endoscopic third ventriculostomy (ETV). This paper explores
the alternative views in the pathophysiology of hydrocephalus and how they
explain the effectiveness of ETV in treating hydrocephalus arising from a variety
of causes.
PMID- 24358423
TI - Should female health providers be involved in medical male circumcision?
Narratives of newly circumcised men in Malawi.
AB - BACKGROUND: The Malawi government has endorsed voluntary medical male
circumcision (VMMC) as a biomedical strategy for HIV prevention after a decade of
debating its effectiveness in the local setting. The "policy" recommends that
male circumcision (MC) should be clinically based, as opposed to the alternative
of traditional male circumcision (TMC). Limited finances, acceptability concerns,
and the health system's limited capacity to meet demand are among the challenges
threatening the mass rollout of VMMC. In terms of acceptability, the gender of
clinicians conducting the operations may particularly influence health facility
based circumcision. This study explored the acceptability, by male clients, of
female clinicians taking part in the circumcision procedure. METHODS: Six focus
group discussions (FGDs) were conducted, with a total of 47 newly circumcised men
from non-circumcising ethnic groups in Malawi participating in this study. The
men had been circumcised at three health facilities in Lilongwe District in 2010.
Data were audio recorded and transcribed verbatim. Data were analysed using
narrative analysis. RESULTS: Participants in the FGDs indicated that they were
not comfortable with women clinicians being part of the circumcising team. While
few mentioned that they were not entirely opposed to female health providers'
participation, arguing that their involvement was similar to male clinicians'
involvement in child delivery, most of them opposed to female involvement,
arguing that MC was not an illness that necessitates the involvement of
clinicians regardless of their gender. Most of the participants said that it was
not negotiable for females to be involved, as they could wait until an all-male
clinician team could be available. Thematically, the arguments against female
clinicians' involvement include sexual undertones and the influences of
traditional male circumcision practices, among others. CONCLUSION: Men preferred
that VMMC should be conducted by male health providers only. Traditionally, male
circumcision has been a male-only affair shrouded in secrecy and rituals.
Although being medical, this study strongly suggested that it may be difficult
for VMMC to immediately move to a public space where female health providers can
participate, even for men coming from traditionally non-circumcising backgrounds.
PMID- 24358425
TI - Physiotherapy in Malawi - a step in the right direction.
AB - Physiotherapists in Malawi are in short supply and the demand for this service is
increasing. This profession is instrumental in the rehabilitation of patients
following accident and disease. Early input from a physiotherapist can be life
changing; for example, timely physiotherapy could prevent a patient from becoming
wheelchair-bound for life. This article explores the role of physiotherapists, in
the context of what they do, the medical conditions that benefit from
physiotherapy and the services available in Malawi. The clinical focus will be on
orthopaedic, musculoskeletal and neurological conditions, since those are the
specialties of the authors. With the start of the physiotherapy degree programme
at the College of Medicine, University of Malawi, huge steps have been taken to
address this neglected profession.
PMID- 24358426
TI - A patient with severe peritonitis.
PMID- 24358427
TI - Infestation of Tunga penetrans in villages near Zomba Central Hospital.
AB - An outbreak of Tunga Penetrans (Jigger Flea) infestation affecting a number of
villages near to a Central Hospital in Malawi is described. Due to the large
number of affected individuals, high parasitic load, and extended duration of
infection an alternative to the recommended approach of surgical removal of the
flea was required. Benzyl benzoate paint and liquid paraffin had been used in
local Primary Healthcare settings previously and topical treatment with
antiparasitic agents has been advocated in the literature, particularly for
severe infestation. Benzyl benzoate and liquid paraffin were applied topically to
four adults with numerous jigger flea burrows, and their progress assessed
regularly. After completion of 7 days of treatment patients noted that fleas were
dislodging spontaneously, and that embedded parasites had not increased in size
to the same extent that untreated fleas had in previous infestations. Following
confirmation of the viability of its implementation in a resource-poor setting,
this treatment regimen has subsequently been adopted by the local branch of the
District Health Office for distribution to infected communities.
PMID- 24358428
TI - The Anaesthetic Friendship Society - supporting anaesthetic clinical officers in
the southern districts of Malawi.
PMID- 24358429
TI - Histoplasmosis in a Malawian patient on ART.
PMID- 24358430
TI - "It is time the masses are sensitised that men too, like women, have reproductive
problems ......" Fanuel Lampiao talks to Thengo Kavinya on his career in
Spermatology.
PMID- 24358431
TI - Have Malawian women embraced the female condom?
PMID- 24358432
TI - Early results from an angiosome-directed open surgical technique for venous
arterialization in patients with critical lower limb ischemia.
AB - BACKGROUND: Patients with critical lower limb ischemia without patent pedal
arteries cannot be treated by the conventional arterial reconstruction. Venous
arterialization has been suggested to improve limb salvage in this subgroup of
patients but has not gained wide acceptance. We report our early experience after
implementing deep and superficial venous arterialization of the lower limb.
MATERIALS AND METHODS: Ten patients with critical ischemia and without crural or
pedal arteries available for conventional bypass surgery or angioplasty were
treated with distal venous arterialization. Inflow was from the most distal
unobstructed segment. Run-off was the dorsal pedal venous arch (n=5), the dorsal
pedal venous arch and a concomitant vein of the posterior tibial artery (n=3), or
the dorsal pedal venous arch and a concomitant vein of the common plantar artery
(n=2) depending on the location of the ischemic lesion. Venous valves were
destroyed using antegrade valvulotomes, guide wires, knob needles, or retrograde
valvulotomes via an extra incision. RESULTS: Seven of the operated limbs were
amputated after 23 (1-256) days (median [range]). The main reasons for amputation
were lack of healing of either the original wound, of incisional wounds on the
foot, or persisting pain at rest. In three cases, the bypass was open at the time
of amputation. Two patients experienced complete wound healing after 231 and 342
days, respectively. By the end of follow-up, the last patient was ambulating with
slow wound healing but without pain 309 days after surgery. CONCLUSION: Venous
arterialization may be used as a treatment of otherwise unsalveable limbs. The
success rate is, however, limited. Technical optimization of the technique is
warranted.
PMID- 24358433
TI - Performance characteristics of three automated immunoassays for thyroid hormones.
AB - BACKGROUND: Since the introduction of the first radioimmunoassay, several
improvements have been made in the design of immunoassays such as method of
antibody production, labeling, automation and detection technology. We performed
an analytical evaluation of the new electrochemiluminescent immunoassay (ECLIA)
for serum TSH, FT4 and T3 in the Elecsys 2010 immunoassay system and compared the
results of this method with those of radioimmunoassay ( RIA) [immunoradiometric
(IRMA) for TSH] and Elisa. METHODS: Fasting serum from 112 hypo, hyper and
euthyroid patients were used to evaluate the minimum detectable concentration,
intra- and inter-assay precisions for TSH, FT4, T3, linearity for TSH assay and
method comparison study. RESULTS: Within the analytical range tested, intra-assay
coefficient of variation was < 2.3% for TSH, 2.3% for FT4 and 7.8% for T3. The
inter-assay coefficient of variation was < 2.9% for TSH, 2.5% for FT4 and 12.3%
for T3. The measurement of diluted sera indicated a desirable percentage of
recovery for TSH. No correlation was found between Elecsys 2010 and Elisa /IRMA
for TSH. The comparison of results of the Elecsys ECLIA assay with those of Elisa
and RIA for T4 were: T4 (ECLIA) = -0.612+0.999, T4 (Elisa, r= 0.88) and T4
(ECLIA)=0.642+0.942 T4 (RIA, r=0.957), while ECLIA assay with Elisa and RIA for
T3 were: T3 (ECLIA)= 0.242+0.908 T3 (Elisa, r=0.8) and T3 (ECLIA) = -0.029+1.01
T3 (RIA, r=0.957). CONCLUSION: The results show that Elecsys 2010 is an automated
reliable, efficient and technically excellent instrument to use in the
measurement of serum TSH, T4 and T3.
PMID- 24358434
TI - Steady state hemoglobin concentration and packed cell volume in homozygous sickle
cell disease patients in Lagos, Nigeria.
AB - BACKGROUND: Sickle cell disease is a genetic disorder of hemoglobin causing
myriad of pathology including anemia. The purpose of this study was to evaluate
the baseline values of steady state hemoglobin and packed cell volume as a guide
to managing the early recognition of hemolytic crises in sickle cell anemia.
METHODS: A cross-sectional study was conducted among the sickle cell patients
attending the Sickle Cell clinic of Lagos State University Teaching Hospital,
Ikeja. A blood sample of 4.5 ml blood was collected from each participant for
hemoglobin concentration and packed cell volume. All blood samples were also
screened for HIV and hemoglobin phenotypes were done using cellulose acetate
hemoglobin electrophoresis at pH 8.6. RESULTS: A total of 98 subjects in steady
state were recruited, consisting of 53 (54.1%) females and 45 (45.9%) males. The
overall means were 7.92+/-1.49 and 24.46+/-4.76; a female mean of 7.73+/-1.45;
23.89+/-4.60, and a male mean of 8.14+/-1.54 and 25.14+/-4.91 were obtained for
hemoglobin and packed cell volume, respectively. Sixty - nine of the 98 (70.40%)
subjects have been previously transfused with blood. CONCLUSION: The mean
hemoglobin concentration and packed cell volume in males was higher than females.
The overall mean was lower than what was expected for age and sex. Over two-third
of sickle cell anemia population had been transfused.
PMID- 24358435
TI - The prevalence of metabolic syndrome according to the Iranian Committee of
Obesity and ATP III criteria in Babol, North of Iran.
AB - BACKGROUND: Metabolic syndrome (MS) is highly significant due to its association
to type 2 diabetes and cardiovascular diseases. The purpose of this study was to
compare the prevalence of MS according to the report of the Iranian National
Committee of Obesity criteria (INCO) versus Adult Treatment Panel III (ATPIII) in
Babol, North of Iran. METHODS: Data obtained based on criteria ATP III from the
Babol Lipid and Glucose Study (from July 2004 to September 2005) and were
compared with the new INCO criteria 2010. The data were collected and analyzed.
RESULTS: In total, 933 adult males and females were evaluated. According to ATP
III criteria, the overall prevalence of metabolic syndrome was 23.7% (95%
confidence interval: 21%-26.4%); 28.4% and 9.4% were females and males,
respectively; however, the prevalence was 20.5% (95% confidence interval: 17.9%
23.1%) according to the INCO criteria, 22.5% and 15.7% were females and males,
respectively. CONCLUSION: The new INCO criteria for the metabolic syndrome
proclaimed by the Iranian Committee of Obesity estimated a lower prevalence of
syndrome in comparison with ATP III criteria in Babol.
PMID- 24358436
TI - Effects of folic acid plus levothyroxine on serum homocysteine level in
hypothyroidism.
AB - BACKGROUND: Rise in serum homocysteine level may be associated with higher
prevalence of cardiovascular diseases in hypothyroidism. Levothyroxine can partly
diminish serum homocysteine level. Folic acid participates in homocysteine
metabolic cycle in the human body. The effect of concomitant administration of
folic acid and levothyroxine on serum homocysteine level was evaluated in the
present study. METHODS: Sixty patients with hypothyroidism participated in this
double-blinded clinical trial study. They were divided into two equal groups;
Group A received oral levothyroxine 50-100 ug daily. Group B took oral folic acid
1 mg on a daily basis in addition to levothyroxine with similar schedule to group
A. The patients were followed up for two months. The serum homocysteine levels of
these two groups were measured before and after the study. This study was
registered in Iranian Registry of clinical trial (IRCT number: 201112077723N1).
RESULTS: Mean serum homocysteine level fell from 11.5+/-4.2 to 9.9+/-3.5 umol/lit
and from 11.2+/-3.1 to 6.9+/-1.9 umol/lit in group A and B, respectively
(p<0.001). The mean reduction in serum homocysteine levels were 1.6+/-1.2
umol/lit and 4.3+/-1.4 umol/lit in group A and B, respectively (p<0.001).
CONCLUSION: Levothyroxine can decrease serum homocysteine level partly; still its
combination with folic acid empowers the effect. Combination therapy declines
serum homocysteine level more successfully.
PMID- 24358437
TI - Pulmonary tuberculosis and diabetes mellitus: Co-existence of both diseases in
patients admitted in a teaching hospital in the southwest of Iran.
AB - BACKGROUND: A number of former studies have shown that tuberculosis (TB) is
higher in diabetes mellitus (DM) patients than non-diabetics. Both DM and TB are
major public health problems in Iran, and because of the lack of investigation in
this field in the region, we conducted this study to evaluate the prevalence of
DM in admitted pulmonary tuberculosis patients. METHODS: The medical files of
documented tuberculosis cases and DM patients hospitalized in Infectious Diseases
Ward in Razi Hospital in Ahvaz, southwest Iran from 2008 to 2010 were reviewed.
The study population was divided into 2 groups as DM-TB and non-DM-TB. The data
in the two groups were compared. RESULTS: One hundred and forty eight TB cases
[36 (24.3%) DM cases with the mean age of 56.6+/-12.7 years, and 112 (75.7%) non
DM with mean age of 44.8+/-18.3 years] were studied. The estimated odds ratio
(OR) of the association between DM and tuberculosis was 2.65 [(95% confidence
interval (CI), 1.77 to 3.95), p<0.001]. There was significant difference in HIV
infection, illicit drug use and imprisonment between the two groups (p<0.05).
CONCLUSION: We found that the frequency of DM in TB patients in the region is
more prevalent than it was expected. Tuberculosis had positive association to DM.
DM might be an important risk factor for developing tuberculosis.
PMID- 24358438
TI - Acute generalized weakness in patients referred to Amirkola Children's Hospital
from 2005 to 2010.
AB - BACKGROUND: Diseases that cause acute flaccid paralysis (AFP) often progress
rapidly, thus may cause life threatening complications, therefore, their
diagnosis and cure are important. This study was carried out to investigate the
causes of acute generalized weakness in children referred to Amirkola Children's
Hospital, in Babol, Iran. METHODS: In this case series, the epidemiological
causes of the disease and clinical features of 15 cases with acute generalized
weakness from April 2005 to September 2010 were evaluated. The data were
collected and analyzed. RESULTS: The mean age of cases was 4.7+/-3.5 years. The
male/female ratio was 2. Twenty cases had Guillain-Barre syndrome, two with
myositis and one with periodic hyperkalemic paralysis. CONCLUSION: Guillain-Barre
syndrome is the most common cause of AFP in children admitted due to acute
generalized weakness in Amirkola Children's Hospital.
PMID- 24358439
TI - The importance of C-reactive protein and other inflammatory markers in patients
with chronic obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease (COPD) is a condition associated with
inflammation in lungs and airways. The impacts of inflammatory process is not
limited to respiratory system but extend to extrapulmonary organs with resultant
complications involving endocrine, metabolic and cardiovascular systems. The
extent and severity of inflammation may be partly estimated by serum measurement
of several markers including serum CRP. Assessment of these markers can be useful
not only for diagnostic or prognostic purpose but also for treatment evaluation
of COPD patients. However, due to inconsistent results of published studies, at
present the diagnostic or prognostic importance of inflammatory markers as well
as their values in the evaluation of treatment outcome has not been accepted by
all investigators. and so their routine applications require further studies.
This review presents data in regard to the status of inflammatory markers at
different stages of COPD patients and evaluates their predictive ability as well
as their values in differential diagnosis or treatment evaluation.
PMID- 24358440
TI - Complete colonic duplication in children.
AB - BACKGROUND: Complete colonic duplication is a very rare congenital anomaly that
may have different presentations according to its location and size. Complete
colonic duplication can occur in 15% of gastrointestinal duplication. We report
two cases of complete colonic duplications, and their characteristics. CASE
PRESENTATION: We present two patients with complete colonic duplication with
different types and presentations. Case 1: A 2- year old boy presented to the
clinic with abdominal protrusion, difficulty to defecate, chronic constipation
and mucosal prolaps covered bulging (rectocele) since he was 6 months old. The
patient had palpable pelvic mass with doughy consistency. Rectal exam confirmed
perirectal mass with soft consistency. The patient underwent a surgical operation
that had total tubular colorectal duplication with one blind end and was treated
with simple fenestration of distal end, and was discharged without complication.
After two years follow up, he had normal defecation and good weight gain. Case 2:
A 2 -day old infant was referred with imperforate anus and complete duplication
of recto-sigmoid colon, diphallus, double bladder, and hypospadiasis. After
clinical and paraclinical investigations, he underwent operations in several
stages in different periods, and was discharged without complications. After four
years follow up, he led a normal life. CONCLUSION: The patients with complete
duplication have to be examined carefully because of the high incidence of other
systemic anomalies. Treatment includes simple resection of distal common wall,
fenestration, and repair other associated anomalies.
PMID- 24358441
TI - Squamous cell carcinoma of lung with unusual site of metastasis.
AB - BACKGROUND: Lung cancer ranks among the most common and most lethal malignancies
worldwide. Once vascular or lymphatic invasions occur, metastatic dissemination
to distant sites is common. Bone, liver, adrenals, and brain are the most
frequent sites of the distant disease. In this study we present a case of
squamous cell carcinoma of lung with metastasis of the left knee bursa. CASE
PRESENTATION: A smoker man presented with cough and hemoptysis and squamous cell
carcinoma of lung was diagnosed. Fourteen months later he developed pain and
swelling of left knee. The biopsy and pathologic examination of the left knee
bursa showed involvement of the bursa. CONCLUSION: Squamous cell carcinoma of
lung can metastasize in the unusual sites of the body.
PMID- 24358442
TI - Crimean-congo hemorrhagic fever: treatment and control strategy in admitted
patients.
PMID- 24358443
TI - Elevated plasma norepinephrine inhibits insulin secretion, but adrenergic
blockade reveals enhanced beta-cell responsiveness in an ovine model of placental
insufficiency at 0.7 of gestation.
AB - In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia
and hypoxemia progressively worsen during the third trimester, which increases
circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block)
at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced beta
cell responsiveness in fetuses with PI-induced intrauterine growth restriction
(IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater
compared with age-matched controls, but the levels were similar to near-term
controls. Therefore, our objective was to determine whether elevations in plasma
NE concentrations inhibit insulin secretion and produce compensatory beta-cell
responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under
basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated
arginine-stimulated insulin secretion (GPAIS) conditions in the absence and
presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus
than in controls, but fetal weights were not different. PI fetuses had lower (P <
0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1
and insulin concentrations and greater plasma NE concentrations (891 +/- 211 v.
292 +/- 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in
controls (0.34 +/- 0.03 v. 1.08 +/- 0.06 ng/ml; P < 0.05). ADR-block increased
GSIS in PI fetuses (1.19 +/- 0.11 ng/ml; P < 0.05) but decreased GSIS in controls
(0.86 +/- 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI
fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses
but not in controls. Insulin content per islet was not different between
treatments. We conclude that elevations in fetal plasma NE suppress insulin
concentrations, and that compensatory beta-cell stimulus-secretion responsiveness
is present before IUGR.
PMID- 24358445
TI - Alkylgold complexes by the intramolecular aminoauration of unactivated alkenes.
AB - Alkylgold(I) complexes were formed from the gold(I)-promoted intramolecular
addition of various amine nucleophiles to alkenes. These experiments provide the
first direct experimental evidence for the elementary step of gold-promoted
nucleophilic addition to an alkene. Deuterium-labeling studies and X-ray crystal
structures provide support for a mechanism involving anti-addition of the
nucleophile to a gold-activated alkene, which is verified by DFT analysis of the
mechanism. Ligand studies indicate that the rate of aminoauration can be
drastically increased by use of electron-poor arylphosphines, which are also
shown to be favored in ligand exchange experiments. Attempts at protodeauration
lead only to recovery of the starting olefins, though the gold can be removed
under reducing conditions to provide the purported hydroamination products.
PMID- 24358444
TI - Oligotyping: Differentiating between closely related microbial taxa using 16S
rRNA gene data.
AB - Bacteria comprise the most diverse domain of life on Earth, where they occupy
nearly every possible ecological niche and play key roles in biological and
chemical processes. Studying the composition and ecology of bacterial ecosystems
and understanding their function is of prime importance. High-throughput
sequencing technologies enable nearly comprehensive descriptions of bacterial
diversity through 16S ribosomal RNA gene amplicons. Analyses of these communities
generally rely upon taxonomic assignments through reference databases, or
clustering approaches using de facto sequence similarity thresholds to identify
operational taxonomic units. However, these methods often fail to resolve
ecologically meaningful differences between closely related organisms in complex
microbial datasets.In this paper we describe oligotyping, a novel supervised
computational method that allows researchers to investigate the diversity of
closely related but distinct bacterial organisms in final operational taxonomic
units identified in environmental datasets through 16S ribosomal RNA gene data by
the canonical approaches.Our analysis of two datasets from two distinct
environments demonstrates the capacity of oligotyping at discriminating distinct
microbial populations of ecological importance.Oligotyping can resolve the
distribution of closely related organisms across environments and unveil
previously overlooked ecological patterns for microbial communities. The URL
http://oligotyping.org offers an open-source software pipeline for oligotyping.
PMID- 24358446
TI - Correlates of disability in depressed older adults with bipolar disorder.
AB - Aims To identify clinical factors associated with disability in depressed older
adults with bipolar disorder (BPD) receiving lamotrigine. Methods Secondary
analysis of a multi-site, 12-week, open-label, uncontrolled study of addon
lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures
included the Montgomery Asberg Depression Rating Scale (MADRS), Young Mania
Rating Scale (YMRS), Cumulative Illness Rating Scale for Geriatrics (CIRS-G),
Dementia Rating Scale (DRS), and WHO-Disability Assessment Scale II (WHO-DAS II).
Results Medical comorbidiy in this group of elders was substantial, with roughly
60% of subjects having disorders of the vascular, musculoskeletal/integument, and
endodrine/metabolic/breast systems. We found significant relationships among mood
(MADRS), medical comorbidity (CIRS-G), cognition (DRS), and disability (WHO-DAS
II). More severe BPD depression, more medical comorbidity and more impaired
cognition were all associated with lower functioning in BPD elders. Conclusions
Our findings fit the paradigm shift that has been occurring in BPD, supporting
the notion that BPD is not solely an illness of mood but that it affects multiple
domains impacting overall functioning.
PMID- 24358447
TI - Cancer genetic counselor information needs for risk communication: a qualitative
evaluation of interview transcripts.
AB - Personalized medicine is a model of healthcare that is predictive, personalized,
preventive and participatory ("P4 Medicine"). Genetic counselors are an ideal
group to study when designing tools to support cancer P4 Medicine activities more
broadly. The goal for this work was to gain a better understanding of the
information cancer genetic counselors seek from their patients to facilitate
effective information exchange for discussing risk. This was an analysis of a
qualitative data set from interviews of eight cancer genetic counselors,
recruited from three institutions. Genetic counselors at each site were
interviewed using a semi-structured, open-ended questionnaire. A selective coding
approach was used to determine major themes associated with genetic counseling
information needs for communicating risk. We generated a model for understanding
categories of genetic counseling information needs to support risk communication
activities. Common activities for risk communication included risk assessment and
tailoring communication. Categories of information needs included: (a) clinical
patient characteristics, (b) social and cognitive patient characteristics and (c)
patient motivation and goals for the genetic counseling session. A logical next
step is for this model to inform the design of software systems for pre-visit
patient planning and delivering just-in-time educational information to
facilitate cancer risk communication activities.
PMID- 24358448
TI - Cultural Beliefs, Intimate Partner Violence and Mental Health Functioning among
Vietnamese Women.
AB - Intimate partner violence (IPV) against women occurs in all countries, with wide
ranging negative effects, including on mental health. IPV rates vary widely
across countries, however, suggesting cultural factors may play a role in IPV.
The primary purpose of the present study was to assess relations among IPV,
mental health symptoms, and cultural beliefs among Vietnamese women, focusing on
moderator effects of cultural beliefs on relations between IPV and mental health.
IPV, anxious and depressive mental health symptoms, and culturally-related
beliefs about IPV were cross-sectionally assessed in 105 married adult Vietnamese
women randomly selected from public population registries in five provinces. IPV
was significantly correlated with anxiety, depression, and suicidal ideation.
Relations were moderated by wives' culturally-related beliefs about abuse (e.g.,
relations between IPV and mental health symptoms were smaller for women who
believed that nothing could be done about abuse). Findings suggest that when
attempting to prevent or treat effects of IPV, it will be important to consider
that certain beliefs about IPV generally viewed as maladaptive (e.g., nothing can
be done about abuse) may have adaptive effects, at least in the short-term, on
relations between IPV and mental health functioning.
PMID- 24358449
TI - Fabrication of Mineralized Collagen from Bovine Waste Materials by Hydrothermal
Method as Promised Biomaterials.
AB - In the present study, we aimed to produce mineralized-collagen by hydrothermal
process. A simple method not depending on additional foreign chemicals has been
employed to isolate the mineralized-collagen fibers from bovine waste. The
process of extraction involves the use of hydrothermal method from available
bovine bones. The structural and morphological properties of the collagen fibers
were characterized by using scanning electron microscopy and transmission
electron microscopy. These results indicated well received collagen fibers,
having a diameter less than 1 MUm and with established mineral content in the
individual fibers. The X-ray diffraction showed the crystalline feature of the
obtained nano-compounds. The thermo gravimetric analysis was used to
differentiate between the collagen and mineral parts of obtained product.
Overall, the results generously indicated production of well received collagen
fibers from bovine bones.
PMID- 24358450
TI - Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia
Associated with Space Exploration.
AB - BACKGROUND: Spaceflight missions may require crewmembers to conduct
Extravehicular Activities (EVA) for repair, maintenance or scientific purposes.
Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure
that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly.
Each EVA is associated with additional challenges such as low levels of total
body cosmic/galactic radiation exposure that may present a threat to crewmember
health and therefore, pose a threat to the success of the mission. We have
developed a murine model of combined, hyperoxia and radiation exposure (double
hit) in the context of evaluating countermeasures to oxidative lung damage
associated with space flight. In the current study, our objective was to
characterize the early and chronic effects of repeated single and double-hit
challenge on lung tissue using a novel murine model of repeated exposure to low
level total body radiation and hyperoxia. This is the first study of its kind
evaluating lung damage relevant to space exploration in a rodent model. METHODS:
Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2
(O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2
and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for
oxidative damage, active TGFbeta1 levels, cell apoptosis, inflammation, injury,
and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure.
RESULTS: Mouse cohorts exposed to all challenge conditions displayed decreased
bodyweight compared to untreated controls at 4 and 8 weeks post-challenge
initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA
(TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell
death and to proteins (nitrotyrosine levels) was elevated all treatment groups.
Importantly, significant systemic oxidative stress was also noted at the late
phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative
damage across all parameters that we measured was significantly higher than
controls in all cohorts but was exacerbated by the combined exposure to O2 and
IR. Additionally, impaired levels of arterial blood oxygenation were noted in all
exposure cohorts. Significant but transient elevation of lung tissue fibrosis
(p<0.05), determined by lung hydroxyproline content, was detected as early as 2
week in mice exposed to challenge conditions and persisted for 4-8 weeks only.
Interestingly, active TGFbeta1 levels in +BAL fluid was also transiently elevated
during the exposure time only (1-4 weeks). Inflammation and lung edema/lung
injury was also significantly elevated in all groups at both early and late time
points, especially the double-hit group. CONCLUSION: We have characterized
significant, early and chronic lung changes consistent with oxidative tissue
damage in our murine model of repeated radiation and hyperoxia exposure relevant
to space travel. Lung tissue changes, detectable several months after the
original exposure, include significant oxidative lung damage (lipid peroxidation,
DNA damage and protein nitrosative stress) and increased pulmonary fibrosis.
These findings, along with increased oxidative stress in diverse body fluids and
the observed decreases in blood oxygenation levels in all challenge conditions
(whether single or in combination), lead us to conclude that in our model of
repeated exposure to oxidative stressors, chronic tissue changes are detected
that persist even months after the exposure to the stressor has ended. This data
will provide useful information in the design of countermeasures to tissue
oxidative damage associated with space exploration.
PMID- 24358451
TI - The LysR Transcription Factor, HexS, Is Required for Glucose Inhibition of
Prodigiosin Production by Serratia marcescens.
AB - Generation of many useful microbe-derived secondary metabolites, including the
red pigment prodigiosin of the bacterium Serratia marcescens, is inhibited by
glucose. In a previous report, a genetic approach was used to determine that
glucose dehydrogenase activity (GDH) is required for inhibiting prodigiosin
production and transcription of the prodigiosin biosynthetic operon (pigA-N).
However, the transcription factor(s) that regulate this process were not
characterized. Here we tested the hypothesis that HexS, a LysR-family
transcription factor similar to LrhA of Escherichia coli, is required for
inhibition of prodigiosin by growth in glucose. We observed that mutation of the
hexS gene in S. marcescens allowed the precocious production of prodigiosin in
glucose-rich medium conditions that completely inhibited prodigiosin production
by the wild type. Unlike previously described mutants able to generate
prodigiosin in glucose-rich medium, hexS mutants exhibited GDH activity and
medium acidification similar to the wild type. Glucose inhibittion of pigA
expression was shown to be dependent upon HexS, suggesting that HexS is a key
transcription factor in secondary metabolite regulation in response to medium pH.
These data give insight into the prodigiosin regulatory pathway and could be used
to enhance the production of secondary metabolites.
PMID- 24358452
TI - ASD-relevant Animal Models of the Foxp Family of Transcription Factors.
AB - Autism is a neurodevelopmental disorder with a multifaceted association between
genes and the environment. Currently, in the majority of patients, the etiology
of autism is not known and coupled with increasing prevalence rates, along with
the high degree of heritability of autism, the development of animal models is
crucial for studying and developing therapies for autism. A key characteristic of
autism is marked abnormalities in the acquisition and use of language. Thus, to
understand and ultimately treat autism is an especially difficult task because no
animal produces language, as it is defined in humans. In this review, we will
discuss the FOXP family of genes, which are a group of transcription factors that
have been linked to both autism, as well as language in humans. Due to the
association of language/communication and the Foxp family of transcription
factors, animal models with targeted disruptions of Foxp functioning are powerful
tools for understanding the developmental signaling pathways that may be
vulnerable in autism.
PMID- 24358453
TI - Vitamin D, Vitamin D Receptor, and Tissue Barriers.
AB - Tissue barriers are critical in the pathogenesis of human diseases, such as
atopic dermatitis, inflammatory bowel diseases, and various cancers. Preserving
or restoring barrier functions of the epithelia cells is a therapeutic strategy
to prevent and treat the illness. Mounting evidence indicates that vitamin D and
the vitamin D receptor (VDR) play key roles in the pathogenesis of human
diseases. In particular, we note an interesting link between vitamin D/VDR
signaling and tissue barriers. In the current review, we summarize the recent
progress on vitamin D and cell junction complexes. We focus on the functions of
VDR and VDR-associated intracellular junction proteins, such as beta-catenin and
claudins. We also discuss the potential therapeutic functions of vitamin D in
treating defective tissue barriers that involve skin, intestine, lung, kidney,
and other organs. However, the mechanisms for the vitamin D/VDR signaling in
tissue barriers remain largely unknown. Further studies on vitamin D/VDR's
multiple functions in physiological models will suggest new therapeutic targets
for prevention and treatment diseases with defective barrier functions.
PMID- 24358455
TI - Alternative Non-Antibody Protein Scaffolds for Molecular Imaging of Cancer.
AB - The development of improved methods for early detection and characterization of
cancer presents a major clinical challenge. One approach that has shown excellent
potential in preclinical and clinical evaluation is molecular imaging with small
scaffold, non-antibody based, engineered proteins. These novel diagnostic agents
produce high contrast images due to their fast clearance from the bloodstream and
healthy tissues, can be evolved to bind a multitude of cancer biomarkers, and are
easily functionalized by site-specific bioconjugation methods. Several small
protein scaffolds have been verified for in vivo molecular imaging including
affibodies and their two-helix variants, knottins, fibronectins, DARPins, and
several natural ligands. Further, the biodistribution of these engineered ligands
can be optimized through rational mutation of the conserved regions, careful
selection and placement of chelator, and modification of molecular size.
PMID- 24358454
TI - Autophagy: An Integral Component of the Mammalian Stress Response.
AB - Mammalian cells and tissues respond to chemical and physical stress by inducing
adaptive or protective mechanisms that prolong survival. Among these, the major
stress inducible proteins (heat shock proteins, glucose regulated proteins, heme
oxygenase-1) provide cellular protection through protein chaperone and/or anti
oxidative and anti-inflammatory functions. In recent years it has become clear
that autophagy, a genetically-programmed and evolutionarily-conserved cellular
process represents another adaptive response to cellular stress. During autophagy
cytosolic material, including organelles, proteins, and foreign pathogens, are
sequestered into membrane-bound vesicles termed autophagosomes, and then
delivered to the lysosome for degradation. Through recycling of cellular
biochemicals, autophagy provides a mechanism for adaptation to starvation. Recent
research has uncovered selective autophagic pathways that target distinct cargoes
to autophagosomes, including mechanisms for the clearance of aggregated protein,
and for the removal of dysfunctional mitochondria (mitophagy). Autophagy can be
induced by multiple forms of chemical and physical stress, including endoplasmic
reticulum stress and oxidative stress, and plays an integral role in the
mammalian stress response. Understanding of the interaction and co-regulation of
autophagy with other stress-inducible systems will be useful in the design and
implementation of therapeutics targeting this pathway.
PMID- 24358456
TI - Streptococcus pneumoniae non-susceptibility and outpatient antimicrobial
prescribing rates at the Alaska Native Medical Center.
AB - BACKGROUND: American Indian/Alaska Native (AI/AN) people suffer substantially
higher rates of invasive pneumococcal disease (IPD) than the general US
population. We evaluated antimicrobial prescribing data and their association
with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people
between 1992 and 2009. METHODS: Antimicrobial use data were gathered from the
electronic patient management system and included all prescriptions dispensed to
Alaska Native patients aged 5 years and older from outpatient pharmacies at the
Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were
gathered from pneumococcal isolates causing IPD among Anchorage Service Unit
AI/AN residents aged 5 years and older. Data were restricted to serotypes not
contained in the pneumococcal vaccine (PCV7). RESULTS: Over the study period,
overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992
to 454/1,000 persons per year in 2009, p<0.001). Trimethoprim/sulfamethoxazole
prescribing increased (43/1,000 persons/year in 1992 to 108/1,000 persons/year in
2009, p<0.001) and non-susceptibility to trimethoprim/sulfamethoxazole in AI/AN
patients >=5 years of age increased in non-PCV7 serotypes (0-12%, p<0.05).
Similarly, prescribing rates increased for macrolide antibiotics (46/1,000
persons/year in 1992 to 84/1,000 persons/year in 2009, p<0.05). We observed no
statistically significant change over time in erythromycin non-susceptibility
among non-PCV7 serotypes in AI/AN patients aged 5 years or greater (0-7%,
p=0.087). CONCLUSION: Antimicrobial prescribing patterns of some antibiotics in
the AI/AN population corresponded to increased antimicrobial resistance in
clinical isolates. This study highlights the on-going threat of antimicrobial
resistance, the critical importance of judicious prescribing of antibiotics and
the potential utility of prescribing data for addressing this issue.
PMID- 24358457
TI - Emotional Distress May Increase Risk for Self-Medication and Lower Risk for Mood
related Drinking Consequences in Adolescents.
AB - The current study examines indicators of emotional distress and coping that may
define sub-populations of adolescents at risk for two potential affect-related
mechanisms underlying substance misuse: self-medication and mood-related drinking
consequences. Although theory and empirical evidence point to the salience of
affect-related drinking to current and future psychopathology, we have little
knowledge of whether or for whom such mood-related processes exist in adolescents
because few studies have used methods that optimally match the phenomenon to the
level of analysis. Consequently, the current study uses multilevel modeling in
which daily reports of negative mood and alcohol use are nested within
individuals to examine whether adolescents with more emotional distress and
poorer coping skills are more likely to evidence self-medication and mood-related
drinking consequences. Seventy-five adolescents participated in a multi-method,
multi-reporter study in which they completed a 21-day experience sampling
protocol assessing thrice daily measures of mood and daily measures of alcohol
use. Results indicate that adolescents reporting greater anger are more likely to
evidence self-medication. Conversely, adolescents displaying lower emotional
distress and more active coping are more likely to evidence mood-related drinking
consequences. Implications for identifying vulnerable sub-populations of
adolescents at risk for these mechanisms of problematic alcohol use are
discussed.
PMID- 24358458
TI - A new nano-optical sensor thin film cadmium sulfide doped in sol-gel matrix for
assessment of alpha-amylase activity in human saliva.
AB - A novel, simple, sensitive and precise spectrofluorimetric method is developed
for measuring the activity of the alpha-amylase enzyme in human saliva. The
remarkable quenching of the luminescence intensity at 634 nm of nano CdS doped in
a sol-gel matrix by various concentrations of maltose (produced from the reaction
of the enzyme with the starch substrate) was successfully used as an optical
sensor for the assessment of alpha-amylase activity. The calibration plot was
achieved over the concentration range 4.8 * 10(-10) to 1.2 * 10(-5) mol L(-1)
maltose with a correlation coefficient of 0.999 and a detection limit of 5.7 *
10(-11) mol L(-1). The method was used satisfactorily for assessment of the alpha
amylase activity in a number of human saliva samples collected from various
healthy volunteers.
PMID- 24358459
TI - Porous layer open tubular columns in capillary liquid chromatography.
AB - This review covers the latest developments and applications of porous layer open
tubular columns in capillary liquid chromatography. Here, the authors provide a
concise background on the fundamentals of porous layer open tubular columns,
their fabrication and application. Over the past two decades, growing interest in
the areas of proteomics and hyphenated LC-MS techniques have played a large part
in the development of porous layer structures within capillary formats due to
their high permeability, excellent efficiency and exceptional peak capacity. This
review gives a brief overview of open tubular columns in general, however, it
focuses predominantly on the applications of covalently bonded porous layer open
tubular columns in liquid chromatography. Open tubular columns containing non
bonded or electrostatically attached layers will not be discussed in detail.
PMID- 24358461
TI - A copper-mediated tandem reaction through isocyanide insertion into N-H bonds:
efficient access to unsymmetrical tetrasubstituted ureas.
AB - A copper-mediated multi-component reaction was developed through isocyanide
insertion into N-H bonds of less active secondary arylamines. This approach leads
to an efficient synthesis of unsymmetrical tetrasubstituted ureas in one pot.
PMID- 24358460
TI - Probing for DNA methylation with a voltammetric DNA detector.
AB - A label-free electrochemical detection of DNA hybridization is used for probing
synthetic methylated ssDNA 27-mer or 33-mer targets from the GSTP1-gene. The
method is based on electrostatic modulation of the anion-exchange kinetics of a
polypyrrole bilayer film deposited on platinum-microelectrodes to which a
synthetic single-stranded 15-mer GSTP-1 promoter probe DNA has been attached (DNA
detector). The effect of the contact of this DNA-detector with non-methylated and
methylated complementary DNA sequences in Tris-buffer is compared using cyclic
voltammetry (CV). The DNA-hybridization taking place at the electrode surface
leads to a significant decrease of the CV area recorded after exposure to
complementary target DNA in comparison to the CV change recorded for non
complementary DNA target. The performance of this miniaturized DNA detector was
optimized with respect to hybridization time, temperature, and concentration of
the target. It was also evaluated with respect to selectivity, sensitivity, and
reproducibility. These results are significant for their possible use as a
screening test for hypermethylated DNA sequences.
PMID- 24358462
TI - Fabrication of a COF-5 membrane on a functionalized alpha-Al2O3 ceramic support
using a microwave irradiation method.
AB - A novel surface modification strategy was developed using 3
aminopropytriethoxysilane and 4-formylphenylboronic acid successively as covalent
linkers between COF-5 and the porous alpha-Al2O3 ceramic support, and then the
COF-5 membrane was further grown successfully on the modified alpha-Al2O3 support
by using a microwave irradiation method.
PMID- 24358463
TI - Polymeric ion-gels containing an amino acid ionic liquid for facilitated CO2
transport media.
AB - Novel ion-gel films containing an amino acid ionic liquid were fabricated by free
radical polymerization of vinyl monomers. These high strength materials
demonstrated superior CO2 permeability and separation performance.
PMID- 24358464
TI - Flexible paper-based ZnO nanorod light-emitting diodes induced multiplexed
photoelectrochemical immunoassay.
AB - ZnO nanorods inorganic-organic heterostructured light-emitting diodes have been
demonstrated on a cheap/disposable paper substrate and applied in multiplexed
photoelectrochemical immunoassay.
PMID- 24358465
TI - Ionic liquid derived carbons as highly efficient oxygen reduction catalysts:
first elucidation of pore size distribution dependent kinetics.
AB - Metal-free N-doped carbons with controllable pore texture were derived from
carbonization of ionic liquid and served as catalysts for oxygen reduction
reaction (ORR) with an activity comparable to that of Pt/C. The investigation
shows that both the ORR activity and kinetics are strongly correlated with the
pore size distribution.
PMID- 24358466
TI - Photochemical dynamics of E-methylfurylfulgide-kinematic effects on
photorelaxation dynamics of furylfulgides.
AB - With the present theoretical study of the photochemical switching of E
methylfurylfulgide we contribute an important step towards the understanding of
the photochemical processes in furylfulgide-related molecules. We have carried
out large-scale, full-dimensional direct semiempirical configuration-interaction
surface-hopping dynamics of the photoinduced ring-closure reaction. Simulated
static and dynamical UV/Vis-spectra show good agreement with experimental data of
the same molecule. By a careful investigation of our dynamical data, we were able
to identify marked differences to the dynamics of the previously studied E
isopropylfurylfulgide. With our simulations we can not only reproduce the
experimentally observed quantum yield differences qualitatively but we can also
pinpoint two reasons for them: kinematics and pre-orientation. With our analysis,
we thus offer straightforward molecular explanations for the high sensitivity of
the photodynamics towards seemingly minor changes in molecular constitution.
Beyond the realm of furylfulgides, these insights provide additional guidance to
the rational design of photochemically switchable molecules.
PMID- 24358467
TI - Roads leading to roam. Role of triple fragmentation and of conical intersections
in photochemical reactions: experiments and theory on methyl formate.
AB - The exploration of alternative roads that open to molecules with sufficient
energy to yield different products permits prediction and eventually control of
the outcomes of chemical reactions. Advanced imaging techniques for monitoring
laser-induced photodissociation are here combined with dynamical simulations,
involving ample sets of classical trajectories generated on a quantum chemical
potential energy surface. Methyl formate, HCOOCH3, is photodissociated at
energies near the triple fragmentation threshold into H, CO and OCH3. Images of
velocity and rotational distributions of CO exhibit signatures of alternative
routes, such as those recently designated as transition-state vs. roaming
mediated. Furthermore, a demonstration of the triple fragmentation route is
given, and also confirmed by H-atom product imaging and FTIR time-resolved
spectra of the intermediate HCO radical. In addition, the relevance of
nonadiabatic transitions promoted by a conical intersection is clarified by
simulations as the privileged "reactivity funnel" of organic photochemistry,
whereby the outcomes of molecular photoexcitation are delivered to electronic
ground states.
PMID- 24358468
TI - Searching for the thermodynamic limit--a DFT study of the step-wise water
oxidation of the bipyramidal Cu7 cluster.
AB - Oxidative degradation of copper in aqueous environments is a major concern in
areas such as catalysis, electronics and construction engineering. A particular
challenge is to systematically investigate the details of this process for non
ideal copper surfaces and particles under the conditions found in most real
applications. To this end, we have used hybrid density functional theory to study
the oxidation of a Cu7 cluster in water solution. Especially, the role of a large
water coverage is explored. This has resulted in the conclusion that, under
atmospheric H2 pressures, the thermodynamically most favored state of degradation
is achieved upon the generation of four H2 molecules (i.e. Cu7 + 8H2O -> Cu7(OH)8
+ 4H2) in both condensed and gas phases. This state corresponds to an average
oxidation state below Cu(I). The calculations suggest that the oxidation reaction
is slow at ambient temperatures with the water dissociation as the rate-limiting
step. Our findings are expected to have implication for, among other areas, the
copper catalyzed water-gas shift reaction, and for the general understanding of
copper corrosion in aqueous environments.
PMID- 24358469
TI - Thermal and energetic processing of ammonia and carbon dioxide bearing solid
mixtures.
AB - We present new experimental results on thermal and ion irradiation processing of
frozen ammonia-carbon dioxide mixtures. Some mixtures were deposited at low
temperatures (T ~ 16 K). Upon warming up to 160 K, complex chemical reactions
occur leading to the formation of new molecules and, in particular, of ammonium
carbamate. We also show that the same species are produced when water is the
dominant species in the ternary mixture with ammonia and carbon dioxide. The
samples have been irradiated with 144 keV S(9+) ions at 16 K and 50 K. Also in
this case, new chemical species are formed as e.g. ammonium formate, CO and OCN(
). The results are discussed in the light of their relevance to the chemical
evolution of ices in the interstellar medium and in the solar system. In
particular, we suggest searching for them among the gas phase species sublimating
from grains around young stellar objects and from the cometary nuclei approaching
the Sun.
PMID- 24358470
TI - Laser-induced graphitization of colloidal nanodiamonds for excellent oxygen
reduction reaction.
AB - Graphitized nanodiamonds were conveniently prepared by the laser irradiation of
colloidal solution using various solvents. The nanodiamonds were converted into a
fully graphitized onion-like structure, which became a cage-like mesoporous
structure by the degradation of graphitic layers. Alcohols, acetone, and
acetonitrile are more efficient solvents for the graphitization compared to water
and hydrocarbons. Therefore the number and morphology of the graphitic layers can
be simply controlled by the solvent and laser-irradiation duration. We suggest a
graphitization model, in which the photocatalytic oxidation of the solvent
accelerates the graphitization of nanodiamonds. The graphitized nanodiamonds were
easily doped with the nitrogen and sulfur atoms in a controlled manner. In
particular, the spherical graphitic layers were preferentially doped with the
pyrrolic nitrogen that enhances remarkably electrocatalytic activity for the
oxygen reduction reaction.
PMID- 24358471
TI - Structural and dynamical characteristics of trehalose and sucrose matrices at
different hydration levels as probed by FTIR and high-field EPR.
AB - Some organisms can survive complete dehydration and high temperatures by adopting
an anhydrobiotic state in which the intracellular medium contains large amounts
of disaccharides, particularly trehalose and sucrose. Trehalose is most effective
also in protecting isolated in vitro biostructures. In an attempt to clarify the
molecular mechanisms of disaccharide bioprotection, we compared the structure and
dynamics of sucrose and trehalose matrices at different hydration levels by means
of high-field W-band EPR and FTIR spectroscopy. The hydration state of the
samples was characterized by FTIR spectroscopy and the structural organization
was probed by EPR using a nitroxide radical dissolved in the respective matrices.
Analysis of the EPR spectra showed that the structure and dynamics of the
dehydrated matrices as well as their evolution upon re-hydration differ
substantially between trehalose and sucrose. The dehydrated trehalose matrix is
homogeneous in terms of distribution of the residual water and spin-probe
molecules. In contrast, dehydrated sucrose forms a heterogeneous matrix. It is
comprised of sucrose polycrystalline clusters and several bulk water domains. The
amorphous form was found only in 30% (volume) of the